PMID- 17332338 TI - Osteopontin promotes integrin activation through outside-in and inside-out mechanisms: OPN-CD44V interaction enhances survival in gastrointestinal cancer cells. AB - Osteopontin (OPN) and splice variants of CD44 (CD44(V)) have independently been identified as markers for tumor progression. In this study, we show that both OPN and CD44(V) are frequently overexpressed in human gastric cancer and that OPN engaged CD44(V) ligation confers cells an increased survival mediated through integrin activation. First, we show that OPN treatment confers cells an increased resistance to UV-induced apoptosis. The OPN-mediated antiapoptosis is dependent on the expression of the variant exon 6 (V6)- or V7-containing CD44 as shown by overexpression of individual CD44(V) in gastric AZ521 cells that express no or very low level of endogenous CD44 and by knockdown of the constitutively expressed V6-containing CD44 isoforms in colon HT29 cells. Although OPN also interacts with RGD integrins, OPN-RGD sequence is dispensable for OPN-mediated antiapoptosis. OPN-induced antiapoptosis is mainly attributed to the engagement of CD44(V) isoforms and the relay of an inside-out signaling via Src activity, leading to robust integrin activation. Furthermore, OPN-elicited antiapoptosis was observed when cells were plated on fibronectin but not on poly-D-lysin, and preincubation of cells with anti-integrin beta(1) antibody to block integrin extracellular matrix (ECM) interaction or ectopic expression of the dominant negative forms of focal adhesion kinase to block ECM-derived signal abolished OPN induced survival, suggesting that OPN-elicited antiapoptotic function is propagated from matrix transduced by integrin. Taken together, we showed that OPN CD44(V) interaction promotes ECM-derived survival signal mediated through integrin activation, which may play an important role in the pathogenic development and progression of gastric cancer. PMID- 17332339 TI - K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling. AB - Mutational activation of the K-Ras oncogene is well established as a key genetic step in the development and growth of pancreatic adenocarcinomas. However, the mechanism by which aberrant Ras signaling promotes uncontrolled pancreatic tumor cell growth remains to be fully elucidated. The recent use of primary human cells to study Ras-mediated oncogenesis provides important model cell systems to dissect this mechanism. We have used a model of telomerase-immortalized human pancreatic duct-derived cells (E6/E7/st) to study mechanisms of Ras growth transformation. First, we found that human papillomavirus E6 and E7 oncogenes, which block the function of the p53 and Rb tumor suppressors, respectively, and SV40 small t antigen were required to allow mutant K-Ras(12D) growth transformation. Second, K-Ras(12D) caused growth transformation in vitro, including enhanced growth rate and loss of density dependency for growth, anchorage independence, and invasion through reconstituted basement membrane proteins, and tumorigenic transformation in vivo. Third, we determined that the Raf, phosphatidylinositol 3-kinase (PI3K), and Ral guanine nucleotide exchange factor effector pathways were activated, although extracellular signal-regulated kinase (ERK) activity was not up-regulated persistently. Finally, pharmacologic inhibition of Raf/mitogen-activated protein kinase/ERK and PI3K signaling impaired K-Ras-induced anchorage-independent growth and invasion. In summary, our studies established, characterized, and validated E6/E7/st cells for the study of Ras-induced oncogenesis. PMID- 17332340 TI - The possible role of cytokeratin 8 in cadmium-induced adaptation and carcinogenesis. AB - Chronic exposures to cadmium compounds are carcinogenic. It was hypothesized that the development of resistance to cadmium may drive carcinogenesis. This is achieved by selection of resistant cells in which the apoptotic response is significantly attenuated. The induction of cadmium resistance in rat lung epithelial cells (LEC) was used to explore the mechanisms of cadmium-induced adaptation and carcinogenesis. Our previous results showed that LECs developed resistance to apoptosis during cadmium adaptation possibly due to perturbation of the c-Jun NH(2)-terminal kinase pathway. Here, we further study these cells by comparative proteomics. Interestingly, we showed that two intermediate filament proteins, cytokeratin 8 (CK8) and cytokeratin 14 (CK14), were increased significantly and stably maintained only in the adapted cells but not in cadmium treated parental cells. It has been documented that CK8/cytokeratin 18 provided resistance to tumor necrosis factor (TNF)-induced apoptosis and CK14 may function as an inhibitor of TNF-TNF receptor 1 (TNFR1) signaling through an association with TNFR1-associated death domain protein, suggesting that up-regulation of CK8 and CK14 may be responsible for apoptotic resistance. Finally, we showed that small interfering RNA-specific knockdown of CK8 in cadmium-adapted cells attenuated the cadmium resistance, indicating the potential role of CK8 in cadmium resistance. This acquired self-resistance to apoptosis could account for cadmium-induced carcinogenesis, as this promotes neoplastic cell survival as well as subsequent clonal expansion and then progression of tumor development. Thus, increased expression of these cytokeratins represents an adaptive survival mechanism that resists cadmium-induced apoptosis and it is unprecedented that cells respond to long-term cadmium exposure by modulating keratin dynamics. PMID- 17332341 TI - GATA-1 is essential in EGF-mediated induction of nucleotide excision repair activity and ERCC1 expression through ERK2 in human hepatoma cells. AB - The nucleotide excision repair (NER) pathway and its leading gene excision-repair cross-complementary 1 (ERCC1) have been shown to be up-regulated in hepatocellular carcinomas even in the absence of treatment with chemotherapeutics. The aim of this study was to determine the mechanism involved in NER regulation during the liver cell growth observed in hepatocellular carcinoma. Both NER activity and ERCC1 expression were increased after exposure to the epidermal growth factor (EGF) in cultured normal and tumoral human hepatocytes. These increases correlated with the activation of the kinase signaling pathway mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK that is known to be a key regulator in the G(1) phase of the hepatocyte cell cycle. Moreover, EGF-mediated activation of ERCC1 was specifically inhibited by either the addition of U0126, a MEK/ERK inhibitor or small interfering RNA-mediated knockdown of ERK2. Basal expression of ERCC1 was decreased in the presence of the phosphoinositide-3-kinase (PI3K) inhibitor and small hairpin RNA (shRNA) against the PI3K pathway kinase FKBP12-rapamycin associated protein or mammalian target of rapamycin. Transient transfection of human hepatocytes with constructs containing different sizes of the 5'-flanking region of the ERCC1 gene upstream of the luciferase reporter gene showed an increase in luciferase activity in EGF-treated cells, which correlated with the presence of the nuclear transcription factor GATA-1 recognition sequence. The recruitment of GATA-1 was confirmed by chromatin immunoprecipitation assay. In conclusion, these results represent the first demonstration of an up-regulation of NER and ERCC1 in EGF-stimulated proliferating hepatocytes. The transcription factor GATA-1 plays an essential role in the induction of ERCC1 through the mitogen-activated protein kinase (MAPK) pathway, whereas the PI3K signaling pathway contributes to ERCC1 basal expression. PMID- 17332342 TI - Insulin receptor substrate-1 regulates the transformed phenotype of BT-20 human mammary cancer cells. AB - Although originating from a human breast cancer, BT-20 cells do not form colonies in soft agar. BT-20 cells do not express insulin receptor substrate-1 (IRS-1), which is known to promote both normal and abnormal growth and to inhibit differentiation. Stable expression of IRS-1 confers to BT-20 cells the ability to form colonies in soft agar. BT-20 cells form tumors in xenografts in mice, but the size of tumors is twice as large when the cells express IRS-1. The increased transformed phenotype is characterized by occupancy of the rDNA and cyclin D1 promoters by IRS-1 and the activation of the cyclin D1, c-myc, and rDNA promoters. In addition, the retinoblastoma protein, which is detectable in the rDNA promoter of quiescent BT-20/IRS-1 cells, is replaced by IRS-1 after insulin like growth factor-I stimulation. Our results indicate that in BT-20 human mammary cancer cells, expression of IRS-1 activates promoters involved in cell growth and cell proliferation, resulting in a more transformed phenotype. Targeting of IRS-1 could be effective in inhibiting the proliferation of mammary cancer cells. PMID- 17332343 TI - Leukemia inhibitory factor: a newly identified metastatic factor in rhabdomyosarcomas. AB - Rhabdomyosarcoma frequently infiltrates bone marrow and this process involves the stromal-derived factor-1 (SDF-1)-CXCR4 axis. Because leukemia inhibitory factor (LIF), like SDF-1, is secreted by bone marrow stroma and directs the regeneration of skeletal muscles, we examined whether the LIF-LIF receptor (LIF-R) axis affects the biology of rhabdomyosarcoma cells. We found that in rhabdomyosarcoma cells, LIF stimulates the following: (a) phosphorylation of mitogen-activated protein kinase p42/44, AKT, and signal transducers and activators of transcription 3, (b) adhesion and chemotaxis, and (c) increased resistance to cytostatics. To compare the biological effects of LIF versus SDF-1, we examined the RH30 cell line, which is highly responsive to both ligands, and found that the chemotaxis of these cells is significantly reduced when the inhibitors of both receptors (T140 for CXCR4 and gp190 blocking antibody for LIF-R) are added simultaneously. Subsequently, by using repetitive chemotaxis to LIF or SDF-1, we selected from the RH30 line subpopulations of cells that respond to LIF but not SDF-1 (RH30-L) or to SDF-1 but not LIF (RH30-S). We found that (a) RH30-L cells seed better to the bone marrow, liver, and lymph nodes of immunodeficient mice than RH30-S cells and (b) mice inoculated i.m. with the RH30-L cells had more rhabdomyosarcoma cells in the bone marrow and lung after 6 weeks. Thus, we present the first evidence that the LIF-LIF-R axis may direct rhabdomyosarcoma metastasis. Further, because we showed that the in vivo metastasis of RH30 cells is inhibited by small interfering RNA against LIF-R, molecular targeting of this axis could become a new strategy to control the metastasis of rhabdomyosarcoma. PMID- 17332344 TI - Down-regulation of apurinic/apyrimidinic endonuclease 1/redox factor-1 expression by soy isoflavones enhances prostate cancer radiotherapy in vitro and in vivo. AB - We previously showed that genistein, the major bioactive component of soy isoflavones, acts as a radiosensitizer and potentiates prostate tumor cell killing by radiation in vitro and in animal tumor models in vivo. However, when given alone in vivo, pure genistein promoted increased lymph node metastasis, which was not observed with a soy isoflavone mixture consisting of genistein, daidzein, and glycitein. In this study, we show that soy inhibit tumor cell growth and potentiates radiation-induced cell killing in vitro like pure genistein. In an orthotopic model, combining soy isoflavones with tumor irradiation inhibited prostate tumor growth. To determine the molecular mechanisms by which soy isoflavones potentiate radiotherapy, we investigated apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) and nuclear factor kappaB (NF-kappaB), two signaling molecules involved in survival pathways. Soy isoflavones decreased APE1/Ref-1 expression in vitro, whereas radiation up regulated it. Pretreatment with soy isoflavones followed by radiation inhibited APE1/Ref-1 expression. APE1/Ref-1 decrease correlated with decreased DNA-binding activity of NF-kappaB mediated by soy isoflavones and radiation, thus promoting cell killing. In vivo treatment of prostate tumors with soy isoflavones and radiation down-regulated APE1/Ref-1 protein expression and NF-kappaB activity, confirming the molecular alterations observed in vitro. The down-regulation of APE1/Ref-1 and NF-kappaB by isoflavones, in vitro and in vivo, supports our hypothesis that these markers represent biological targets of isoflavones. Indeed, a 2-fold increase in APE1/Ref-1 expression, obtained by cDNA transfection, resulted in a 2-fold increase in NF-kappaB DNA-binding activity, and both of which were down-regulated by soy isoflavones, confirming the cross talk between these molecules and, in turn, causing radiosensitization. PMID- 17332345 TI - Metabolomics by proton nuclear magnetic resonance spectroscopy of the response to chloroethylnitrosourea reveals drug efficacy and tumor adaptive metabolic pathways. AB - Metabolomics of tumors may allow discovery of tumor biomarkers and metabolic therapeutic targets. Metabolomics by two-dimensional proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy was applied to investigate metabolite disorders following treatment by chloroethylnitrosourea of murine B16 melanoma (n = 33) and 3LL pulmonary carcinoma (n = 31) in vivo. Treated tumors of both types resumed growth after a delay. Nitrosoureas provoke DNA damage but the metabolic consequences of genotoxic stress are little known yet. Although some differences were observed in the metabolite profile of untreated tumor types, the prominent metabolic features of the response to nitrosourea were common to both. During the growth inhibition phase, there was an accumulation of glucose (more than x10; P < 0.05), glutamine (x3 to 4; P < 0.01), and aspartate (x2 to 5; P < 0.01). This response testified to nucleoside de novo synthesis down-regulation and drug efficacy. However, this phase also involved the increase in alanine (P < 0.001 in B16 melanoma), the decrease in succinate (P < 0.001), and the accumulation of serine-derived metabolites (glycine, phosphoethanolamine, and formate; P < 0.01). This response witnessed the activation of pathways implicated in energy production and resumption of nucleotide de novo synthesis, thus metabolic pathways of DNA repair and adaptation to treatment. During the growth recovery phase, it remained polyunsaturated fatty acid accumulation (x1.5 to 2; P < 0.05) and reduced utilization of glucose compared with glutamine (P < 0.05), a metabolic fingerprint of adaptation. Thus, this study provides the proof of principle that metabolomics of tumor response to an anticancer agent may help discover metabolic pathways of drug efficacy and adaptation to treatment. PMID- 17332346 TI - Mammalian target of rapamycin inhibitors as possible adjuvant therapy for microscopic residual disease in head and neck squamous cell cancer. AB - Molecular therapeutics identifies an aberration in tumors to select patients that benefit from molecular targeted therapy. Overexpression of eIF4E in histologically "tumor-free" surgical margins of head and neck squamous cell cancer (HNSCC) patients is an independent predictor of recurrence and is functionally activated through the Akt/mammalian target of rapamycin (mTOR) pathway. Although mTOR inhibitors are cytostatic agents, best used in combination therapy, we hypothesize that they can be used as long-term single agents in an HNSCC model of minimal residual disease (MRD). CCI-779, an mTOR inhibitor, arrested growth of a phosphatase and tensin homologue deleted on chromosome 10 (PTEN) abnormal HNSCC cell line FaDu, inhibiting phosphorylation of 4E-binding protein 1, resulting in increased association with eIF4E and inhibition of basic fibroblast growth factor and vascular endothelial growth factor. Fluorescence in situ hybridization detected PTEN abnormalities in 68% of patient tumors and 35% of tumor-free margins. CCI-779 inhibited growth of established tumors in nude mice. However, in the MRD model, there were significant differences in the tumor free rate between the control (4%) and the treatment group (50%), and the median tumor-free time was 7 versus 18 days, respectively (P < 0.0001). In those animals that formed tumors, CCI-779 caused a significant decrease in the tumor volume. The Kaplan-Meier curve showed that CCI-779 significantly increased survival (P < 0.0001). The mTOR pathway was inhibited in peripheral blood mononuclear cells potential surrogate markers of response to therapy. Stable transfection of FaDu with luciferase allowed us to monitor the effects of CCI-779 with bioluminescence imaging in the MRD model. These results pave the way for a clinical trial using targeted molecular therapy with CCI-779 as a single agent for mTOR-activated residual cells. PMID- 17332347 TI - High-throughput screening identifies novel agents eliciting hypersensitivity in Fanconi pathway-deficient cancer cells. AB - Inactivation of the Fanconi anemia (FA) pathway occurs in diverse human tumors among the general population and renders those tumors hypersensitive to DNA interstrand-cross-linking (ICL) agents. The identification of novel agents to which FA pathway-deficient cells were hypersensitive could provide new therapeutic opportunities and improve our molecular understanding of the FA genes. Using high-throughput screening, we assessed the growth of isogenic human cancer cells that differed only in the presence or absence of single FA genes upon treatment with 880 active drugs and 40,000 diverse compounds. We identified several compounds to which FA pathway-deficient cells were more sensitive than FA pathway-proficient cells, including two groups of structurally related compounds. We further investigated the compound eliciting the strongest effect, termed 80136342. Its mechanism of action was distinct from that of ICL agents; 80136342 did not cause increased chromosomal aberrations, enhanced FANCD2 monoubiquitination, H2AX phosphorylation, p53 activation, or ICL induction. Similar to ICL agents, however, 80136342 caused a pronounced G(2) arrest in FA pathway-deficient cells. When applied in combination with ICL agents, 80136342 had at least additive toxic effects, excluding interferences on ICL-induced toxicity and facilitating a combinational application. Finally, we identified one particular methyl group necessary for the effects of 80136342 on FA-deficient cells. In conclusion, using high-throughput screening in an isogenic human FA cancer model, we explored a novel approach to identify agents eliciting hypersensitivity in FA pathway-deficient cells. We discovered several attractive candidates to serve as lead compounds for evaluating structure-activity relationships and developing therapeutics selectively targeting FA pathway deficient tumors. PMID- 17332348 TI - Synthetic affibody molecules: a novel class of affinity ligands for molecular imaging of HER2-expressing malignant tumors. AB - The Affibody molecule Z(HER2:342-pep2), site-specifically and homogeneously conjugated with a 1,4,7,10-tetra-azacylododecane-N,N',N'',N'''-tetraacetic acid (DOTA) chelator, was produced in a single chemical process by peptide synthesis. DOTA-Z(HER2:342-pep2) folds spontaneously and binds HER2 with 65 pmol/L affinity. Efficient radiolabeling with >95% incorporation of (111)In was achieved within 30 min at low (room temperature) and high temperatures (up to 90 degrees C). Tumor uptake of (111)In-DOTA-Z(HER2:342-pep2) was specific for HER2-positive xenografts. A high tumor uptake of 23% injected activity per gram tissue, a tumor to-blood ratio of >7.5, and high-contrast gamma camera images were obtained already 1 h after injection. Pretreatment with Herceptin did not interfere with tumor targeting, whereas degradation of HER2 using the heat shock protein 90 inhibitor 17-allylamino-geldanamycin before administration of (111)In-DOTA Z(HER2:342-pep2) obliterated the tumor image. The present results show that radiolabeled synthetic DOTA-Z(HER2:342-pep2) has the potential to become a clinically useful radiopharmaceutical for in vivo molecular imaging of HER2 expressing carcinomas. PMID- 17332349 TI - Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. AB - In the context of pancreatic cancer, metastasis remains the most critical determinant of resectability, and hence survival. The objective of this study was to determine whether Hedgehog (Hh) signaling plays a role in pancreatic cancer invasion and metastasis because this is likely to have profound clinical implications. In pancreatic cancer cell lines, Hh inhibition with cyclopamine resulted in down-regulation of snail and up-regulation of E-cadherin, consistent with inhibition of epithelial-to-mesenchymal transition, and was mirrored by a striking reduction of in vitro invasive capacity (P < 0.0001). Conversely, Gli1 overexpression in immortalized human pancreatic ductal epithelial cells led to a markedly invasive phenotype (P < 0.0001) and near total down-regulation of E cadherin. In an orthotopic xenograft model, cyclopamine profoundly inhibited metastatic spread; only one of seven cyclopamine-treated mice developed pulmonary micrometastases versus seven of seven mice with multiple macrometastases in control animals. Combination of gemcitabine and cyclopamine completely abrogated metastases while also significantly reducing the size of "primary" tumors. Gli1 levels were up-regulated in tissue samples of metastatic human pancreatic cancer samples compared with matched primary tumors. Aldehyde dehydrogenase (ALDH) overexpression is characteristic for both hematopoietic progenitors and leukemic stem cells; cyclopamine preferentially reduced "ALDH-high" cells by approximately 3-fold (P = 0.048). We confirm pharmacologic Hh pathway inhibition as a valid therapeutic strategy for pancreatic cancer and show for the first time its particular efficacy against metastatic spread. By targeting specific cellular subpopulations likely involved in tumor initiation at metastatic sites, Hh inhibitors may provide a new paradigm for therapy of disseminated malignancies, particularly when used in combination with conventional antimetabolites that reduce "bulk" tumor size. PMID- 17332350 TI - Computational modeling and experimental evaluation of a novel prodrug for targeting the extracellular space of prostate tumors. AB - We are developing a noninvasive approach for targeting imaging and therapeutic radionuclides to prostate cancer. Our method, Enzyme-Mediated Cancer Imaging and Therapy (EMCIT), aims to use enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule within the extracellular space of solid tumors. Advanced methods for data mining of the literature, protein databases, and knowledge bases (IT. Omics LSGraph and Ingenuity Systems) identified prostatic acid phosphatase (PAP) as an enzyme overexpressed in prostate cancer and secreted in the extracellular space. Using AutoDock 3.0 software, the prodrug ammonium 2-(2'-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone (IQ(2-P)) was docked in silico into the X-ray structure of PAP. The data indicate that IQ(2-P) docked into the PAP active site with a calculated inhibition constant (K(i)) more favorable than that of the PAP inhibitor alpha-benzylaminobenzylphosphonic acid. When (125)IQ(2-P), the radioiodinated form of the water-soluble prodrug, was incubated with PAP, rapid hydrolysis of the compound was observed as exemplified by formation of the water-insoluble 2-(2'-hydroxyphenyl)-6-[(125)I]iodo-4-(3H) quinazolinone ((125)IQ(2-OH)). Similarly, the incubation of IQ(2-P) with human LNCaP, PC-3, and 22Rv1 prostate tumor cells resulted in the formation of large fluorescent IQ(2-OH) crystals. No hydrolysis was seen in the presence of normal human cells. Autoradiography of tumor cells incubated with (125)IQ(2-P) showed accumulation of radioactive grains ((125)IQ(2-OH)) around the cells. We anticipate that the EMCIT approach will enable the active in vivo entrapment of radioimaging and radiotherapeutic compounds within the extracellular spaces of primary prostate tumors and their metastases. PMID- 17332351 TI - In vitro biological characterization of a novel, synthetic diaryl pyrazole resorcinol class of heat shock protein 90 inhibitors. AB - The molecular chaperone heat shock protein 90 (HSP90) has emerged as an exciting molecular target. Derivatives of the natural product geldanamycin, such as 17 allylamino-17-demethoxy-geldanamycin (17-AAG), were the first HSP90 ATPase inhibitors to enter clinical trial. Synthetic small-molecule HSP90 inhibitors have potential advantages. Here, we describe the biological properties of the lead compound of a new class of 3,4-diaryl pyrazole resorcinol HSP90 inhibitor (CCT018159), which we identified by high-throughput screening. CCT018159 inhibited human HSP90beta with comparable potency to 17-AAG and with similar ATP competitive kinetics. X-ray crystallographic structures of the NH(2)-terminal domain of yeast Hsp90 complexed with CCT018159 or its analogues showed binding properties similar to radicicol. The mean cellular GI(50) value of CCT018159 across a panel of human cancer cell lines, including melanoma, was 5.3 mumol/L. Unlike 17-AAG, the in vitro antitumor activity of the pyrazole resorcinol analogues is independent of NQO1/DT-diaphorase and P-glycoprotein expression. The molecular signature of HSP90 inhibition, comprising increased expression of HSP72 protein and depletion of ERBB2, CDK4, C-RAF, and mutant B-RAF, was shown by Western blotting and quantified by time-resolved fluorescent-Cellisa in human cancer cell lines treated with CCT018159. CCT018159 caused cell cytostasis associated with a G(1) arrest and induced apoptosis. CCT018159 also inhibited key endothelial and tumor cell functions implicated in invasion and angiogenesis. Overall, we have shown that diaryl pyrazole resorcinols exhibited similar cellular properties to 17-AAG with potential advantages (e.g., aqueous solubility, independence from NQO1 and P-glycoprotein). These compounds form the basis for further structure-based optimization to identify more potent inhibitors suitable for clinical development. PMID- 17332352 TI - Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine. AB - Vincristine is a microtubule-destabilizing antimitotic drug that has been used in cancer therapy for over 40 years. However, the knowledge on vincristine-induced cell death pathways is still sparse. Here, we show that vincristine induces dramatic changes in the lysosomal compartment and sensitizes cells to lysosomal membrane permeabilization. In HeLa cervix carcinoma cells, vincristine induced mitotic arrest and massive cell death associated with an early increase in the lysosomal volume and lysosomal leakage followed by the activation of the intrinsic apoptosis program. In contrast, the majority of vincristine-treated MCF 7 breast carcinoma cells resisted apoptosis. Instead, they adapted to the spindle assembly checkpoint and escaped the mitotic arrest as micronucleated and senescent cells with an increase in the volume and the activity of their lysosomal compartment. Consistent with its substantial effects on the lysosomes, vincristine greatly sensitized cultured cancer cells as well as orthotopic breast cancer xenografts in mice to the cytotoxicity induced by siramesine, a sigma-2 receptor ligand that kills cancer cells by destabilizing their lysosomes. Importantly, the combination of nontoxic concentrations of vincristine and siramesine resulted in massive cell death even in MCF-7 cells that were capable of escaping vincristine-induced spindle assembly checkpoint and cell death. Similar synergism was observed when siramesine was combined with a semisynthetic vincristine analogue, vinorelbine, or with microtubule-stabilizing paclitaxel. These data strongly suggest that combination therapies consisting of microtubule disturbing and lysosome-destabilizing drugs may prove useful in the treatment of otherwise therapy-resistant human cancers. PMID- 17332353 TI - Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection. AB - Dasatinib is a multitargeted kinase inhibitor that was recently approved for the treatment of chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy. It is also in clinical trials for treating patients with solid tumors. The identification of molecular markers predictive of response to dasatinib could assist in clinical development by selecting patients most likely to derive clinical benefit. Using baseline gene expression profiling of a panel of 23 breast cancer cell lines, we identified genomic signatures highly correlated with in vitro sensitivity to dasatinib. The ability of these signatures to predict dasatinib sensitivity was further confirmed and validated in independent test cell lines. A six-gene model was used to correctly predict dasatinib sensitivity in 11 out of 12 (92%) additional breast and 19 out of 23 (83%) lung cancer cell lines. Quantitative real-time PCR and immunohistochemical assays further confirmed the differential expression pattern of selected markers. Finally, these gene signatures were observed in a subset of primary breast, lung, and ovarian tumors suggesting potential utility in patient selection. The subset of breast cancer patients expressing the dasatinib-sensitive signature includes a distinct clinical and molecular subgroup: the so-called "triple negative" (i.e., estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) or "basal" breast cancer subtype. This patient population has a poor prognosis and currently has few effective treatment options. Our results implicate that dasatinib may represent a valuable treatment option in this difficult-to-treat population. To test this hypothesis, clinical studies are now under way to determine the activity of dasatinib in these patients. PMID- 17332354 TI - Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. AB - Previous studies, including those from our laboratory, have revealed that phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables, not only affords significant protection against chemically induced cancer in animal models but also inhibits growth of cancer cells in culture and in vivo by causing cell cycle arrest and apoptosis induction. We now report a novel response to PEITC involving inhibition of angiogenesis in vitro and ex vivo at pharmacologically achievable concentrations. The PEITC treatment caused a decrease in survival of human umbilical vein endothelial cells (HUVEC) in a concentration- and time-dependent manner. The capillary-like tube structure formation (in vitro neovascularization) and migration (invasion potential) by HUVEC was also inhibited significantly in the presence of PEITC at pharmacologically relevant concentrations (<1 mumol/L). The PEITC-mediated inhibition of angiogenic features of HUVEC in vitro was associated with suppression of vascular endothelial growth factor (VEGF) secretion, down regulation of VEGF receptor 2 protein levels, and inactivation of prosurvival serine-threonine kinase Akt. The PEITC treatment reduced migration by PC-3 human prostate cancer cells, which correlated with inactivation of Akt and suppression of VEGF, epidermal growth factor (EGF), and granulocyte colony-stimulating factor (G-CSF) secretion. The PEITC-mediated inhibition of PC-3 cell migration was statistically significantly attenuated by ectopic expression of constitutively active Akt. Most importantly, PEITC treatment inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay. In conclusion, the present study suggests that inhibition of angiogenesis may be an important mechanism in cancer chemoprevention by PEITC. PMID- 17332355 TI - MG-132 sensitizes TRAIL-resistant prostate cancer cells by activating c-Fos/c-Jun heterodimers and repressing c-FLIP(L). AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because it induces apoptosis in cancer cells but not in normal cells. Unfortunately, some cancer cells develop resistance to TRAIL-induced apoptosis. Therefore, it is clinically relevant to determine the molecular mechanisms that differentiate between TRAIL-sensitive and TRAIL-resistant tumors. Previously, we have shown that the antiapoptotic molecule cellular-FLICE inhibitory protein long isoform [c-FLIP(L)] is necessary and sufficient to maintain resistance to TRAIL-induced apoptosis. We have found that c-FLIP(L) is transcriptionally regulated by the activator protein-1 (AP-1) family member protein c-Fos. Here, we report that MG-132, a small-molecule inhibitor of the proteasome, sensitizes TRAIL-resistant prostate cancer cells by inducing c-Fos and repressing c-FLIP(L). c-Fos, which is activated by MG-132, negatively regulates c-FLIP(L) by direct binding to the putative promoter region of the c FLIP(L) gene. In addition to activating c-Fos, MG-132 activates another AP-1 family member, c-Jun. We show that c-Fos heterodimerizes with c-Jun to repress transcription of c-FLIP(L). Therefore, MG-132 sensitizes TRAIL-resistant prostate cancer cells by activating the AP-1 family members c-Fos and c-Jun, which, in turn, repress the antiapoptotic molecule c-FLIP(L). PMID- 17332357 TI - CD28 costimulation overcomes transforming growth factor-beta-mediated repression of proliferation of redirected human CD4+ and CD8+ T cells in an antitumor cell attack. AB - The T-cell-mediated antitumor immune response is frequently repressed in the tumor environment by an immunologic barrier, the predominant mediators of which are thought to be interleukin-10 (IL-10) and transforming growth factor-beta (TGF beta). We explored the effect of these cytokines on the individual T-cell effector functions on antigen engagement during an antitumor cell attack. Isolated CD4+ and CD8+ T cells were antigen-specifically redirected toward carcinoembryonic antigen (CEA)-positive tumor cells by expression of a recombinant T-cell receptor (immunoreceptor), which triggers T-cell activation via CD3zeta on binding to CEA. Immunoreceptor-activated T cells secrete IFN gamma, proliferate, and lyse CEA+ but not CEA- tumor cells. Whereas IL-10 has no direct effect on immunoreceptor-triggered effector functions, TGF-beta represses proliferation of both CD4+ and CD8+ T cells but neither IFN-gamma secretion nor specific cytolytic activities. CD28 costimulation, however, overcomes TGF-beta mediated repression in T-cell proliferation. Consequently, T cells redirected by a combined CD28-CD3zeta signaling immunoreceptor are largely resistant to TGF beta-mediated repression. This is reflected in vivo by a more pronounced antitumor activity of T cells against TGF-beta-secreting tumors when redirected by a costimulatory CD28-CD3zeta than by a CD3zeta signaling immunoreceptor. PMID- 17332356 TI - Histone deacetylase inhibitors synergize p300 autoacetylation that regulates its transactivation activity and complex formation. AB - p300/cyclic AMP-responsive element binding protein-binding protein (CBP) are general coactivators for multiple transcription factors involved in various cellular processes. Several highly conserved domains of p300/CBP serve as interacting sites for transcription factors and regulatory proteins. Particularly, the intrinsic histone acetyltransferase (HAT) activity and transactivation domains (TAD) play essential roles for their coactivating function. Autoacetylation of p300/CBP is commonly observed in cell-free HAT assays and has been implicated in the regulation of their HAT activity. Here, we show that six lysine-rich regions in several highly conserved functional domains of p300 are targeted by p300HAT for acetylation in cell-free systems. We show that p300 is susceptible to acetylation in cultured tumor cells and that its acetylation status is affected by histone deacetylase inhibitor trichostatin A. We further show that either treatment with deacetylase inhibitors or coexpression of Gal4-p300HAT, which alone has no transactivation activity, stimulates the activity of the COOH-terminal TAD of p300 (p300C-TAD). We have defined the minimal p300C-TAD and show that it is sufficient to respond to deacetylase inhibitors and is a substrate for p300HAT. Finally, we show that acetylated p300 possesses enhanced ability to interact with p53. Taken together, our data suggest that acetylation regulates p300C-TAD and that acetylation of p300/CBP may contribute to the dynamic regulation of their complex formation with various interacting partners. PMID- 17332358 TI - Homeodomain-interacting protein kinase 2 is the ionizing radiation-activated p53 serine 46 kinase and is regulated by ATM. AB - Phosphorylation of p53 at Ser(46) is important to activate the apoptotic program. The protein kinase that phosphorylates p53 Ser(46) in response to DNA double strand breaks is currently unknown. The identification of this kinase is of particular interest because it may contribute to the outcome of cancer therapy. Here, we report that ionizing radiation (IR) provokes homeodomain-interacting protein kinase 2 (HIPK2) accumulation, activation, and complex formation with p53. IR-induced HIPK2 up-regulation strictly correlates with p53 Ser(46) phosphorylation. Down-regulation of HIPK2 by RNA interference specifically inhibits IR-induced phosphorylation of p53 at Ser(46). Moreover, we show that HIPK2 activation after IR is regulated by the DNA damage checkpoint kinase ataxia telangiectasia mutated (ATM). Cells from ataxia telangiectasia patients show defects in HIPK2 accumulation. Concordantly, IR-induced HIPK2 accumulation is blocked by pharmacologic inhibition of ATM. Furthermore, ATM down-regulation by RNA interference inhibited IR-induced HIPK2 accumulation, whereas checkpoint kinase 2 deficiency showed no effect. Taken together, our findings indicate that HIPK2 is the IR-activated p53 Ser(46) kinase and is regulated by ATM. PMID- 17332359 TI - Targeting the oligomerization domain of ETO interferes with RUNX1/ETO oncogenic activity in t(8;21)-positive leukemic cells. AB - About 12% of all de novo acute myeloid leukemias are characterized by the translocation t(8;21), which generates the oncogenic fusion protein RUNX1/ETO. RUNX1/ETO has a modular structure and contains several docking sites for heterologous proteins, including transcriptional co-repressors like N-CoR, SMART, and mSIN3A. RUNX1/ETO is found in high molecular weight complexes, which are crucial for the block in myeloid differentiation observed in RUNX1/ETO transformed cells. Essential for high molecular weight complex formation is the nervy homology region 2 (NHR2) within ETO, which serves as interacting surface for oligomerization as well as association with members of the ETO protein family. Here, we show that the expression of a fusion peptide consisting of 128 amino acids (NC128), including the entire NHR2 domain of ETO, disrupts the stability of the RUNX1/ETO high molecular weight complexes, restores transcription of RUNX1/ETO target genes, and reverts the differentiation block induced by RUNX1/ETO in myeloid cells. In the presence of NC128, RUNX1/ETO transformed cells lose their progenitor cell characteristics, are arrested in cell cycle progression, and undergo cell death. Our results indicate that selective interference with the oligomerization domain of ETO could provide a promising strategy to inhibit the oncogenic properties of the leukemia-associated fusion protein RUNX1/ETO. PMID- 17332360 TI - Attenuation of the glucocorticoid response during Ad5IL-12 adenovirus vector treatment enhances natural killer cell-mediated killing of MHC class I-negative LNCaP prostate tumors. AB - Tumor cells can evolve to evade immune responses by down-modulating surface MHC class I expression and become refractory to T cell-directed immunotherapy. We employed a strategy to bypass this escape mechanism using a recombinant adenovirus vector expressing interleukin-12 (Ad5IL-12) to target natural killer (NK) cell-mediated killing of human prostate tumors in NOD.scid mice. Fluorescence-activated cell sorting analysis revealed that LNCaP tumor cells bear negligible levels of MHC class I molecules; yet, they express MICA/B molecules, ligands for the NKG2D receptors found on NK cells. Transduction of LNCaP cells with the Ad5IL-12 vector prevented tumor formation in NOD.scid mice, indicating that NK cells alone can conduct tumor immunosurveillance and mediate protection. Intratumor injection of the Ad5IL-12 vector to established LNCaP tumors in NOD.scid mice resulted in a significant delay of tumor growth mediated by NK cell killing activity. The dependency of NK cells in this protective response was shown by the complete loss of Ad5IL-12 therapeutic efficacy on LNCaP tumors established in NOD.Cg-Rag1(tm1Mom)Prf1(tm1Sdz) congenic mice, which are devoid of NK cell activity. More pronounced attenuation of tumor growth and enhanced NK killing activity was observed when pharmacologic adrenalectomy with mitotane was done in combination with Ad5IL-12 vector treatment. The Ad5IL-12 vector treatment also induced killing of MICA/B-negative MHC class I-positive PC3 tumors formed in NOD.scid mice. Together, these results indicate that a targeted NK cell response could provide a generic approach for cancer immunotherapy, and that enhancing the NK cell response via control of cortisol levels may provide an additional therapeutic avenue in cancer. PMID- 17332361 TI - Metabotropic glutamate receptor 1 and glutamate signaling in human melanoma. AB - Recently, several laboratories have started to investigate the involvement of glutamate signaling in cancer. In previous studies, we reported on a transgenic mouse model that develops melanoma spontaneously. Subsequent studies in these mice identified that the aberrant expression of metabotropic glutamate receptor 1 (GRM1) in melanocytes played a critical role in the onset of melanoma. Confirmation of the etiologic role of GRM1 in melanoma development was shown in a second transgenic line with GRM1 expression under the regulation of a melanocyte specific dopachrome tautomerase promoter. Ectopic expression of GRM1 was also detected in a subset of human melanoma cell lines and biopsies, suggesting that aberrant expression of GRM1 in melanocytes may contribute to the development of human melanoma. GRM1, a seven-transmembrane domain G protein-coupled receptor, is normally expressed and functional in neuronal cells, and its ligand, glutamate, is the major excitatory neurotransmitter. Human melanoma cells are shown here to release elevated levels of glutamate, implying a possible autocrine loop. Treatment of GRM1-expressing human melanoma cells with a GRM1 antagonist (LY367385 or BAY36-7620) or a glutamate release inhibitor (riluzole) leads to a suppression of cell proliferation as well as a decrease in levels of extracellular glutamate. Treatment of human melanoma cell xenografts with riluzole for 18 days via p.o. gavage or i.v. injection leads to inhibition of tumor growth by 50% in comparison with controls. These data suggest the importance of glutamate signaling in human melanoma and imply that the suppression of glutamate signaling may be a new target for melanoma therapy. PMID- 17332362 TI - New soft alkylating agents with enhanced cytotoxicity against cancer cells resistant to chemotherapeutics and hypoxia. AB - Chloroethylureas (CEU) are soft alkylating agents that covalently bind to beta tubulin (betaTAC) and affect microtubule polymerization dynamics. Herein, we report the identification of a CEU subset and its corresponding oxazolines, which induce cell growth inhibition, apoptosis, and microtubule disruption without alkylating beta-tubulin (N-betaTAC). Both betaTAC and N-betaTAC trigger the collapse of mitochondrial potential (DeltaPsi(m)) and modulate reactive oxygen species levels, following activation of intrinsic caspase-8 and caspase-9. Experiments using human fibrosarcoma HT1080 respiratory-deficient cells (rho(0)) and uncoupler of the mitochondrial respiratory chain (MRC) showed that betaTAC and N-betaTAC impaired the MRC. rho(0) cells displayed an increased sensitivity toward N-betaTAC as compared with rho(+) cells but, in contrast, were resistant to betaTAC or classic chemotherapeutics, such as paclitaxel. Oxazoline-195 (OXA 195), an N-betaTAC derivative, triggered massive swelling of isolated mitochondria. This effect was insensitive to cyclosporin A and to Bcl-2 addition. In contrast, adenine nucleotide translocator (ANT) antagonists, bongkrekic acid or atractyloside, diminished swelling induced by OXA-195. The antiproliferative activities of the N-betaTACs CEU-025 and OXA-152 were markedly decreased in the presence of atractyloside. Conversely, pretreatment with cyclosporin A enhanced growth inhibition induced by betaTAC and N-betaTAC. One of the proteins alkylated by N-betaTAC was identified as the voltage-dependent anion channel isoform-1, an ANT partner. Our results suggest that betaTAC and N-betaTAC, despite their common ability to affect the microtubule network, trigger different cytotoxic mechanisms in cancer cells. The role of mitochondria in these mechanisms and the potential of N-betaTAC as a new therapeutic approach for targeting hypoxia-resistant cells are discussed. PMID- 17332363 TI - Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. AB - Melanoma has a propensity to metastasize to bone, where it is exposed to high concentrations of transforming growth factor-beta (TGF-beta). Because TGF-beta promotes bone metastases from other solid tumors, such as breast cancer, we tested the role of TGF-beta in melanoma metastases to bone. 1205Lu melanoma cells, stably transfected to overexpress the natural TGF-beta/Smad signaling inhibitor Smad7, were studied in an experimental model of bone metastasis whereby tumor cells are inoculated into the left cardiac ventricle of nude mice. All mice bearing parental and mock-transfected 1205Lu cells developed osteolytic bone metastases 5 weeks post-tumor inoculation. Mice bearing 1205Lu-Smad7 tumors had significantly less osteolysis on radiographs and longer survival compared with parental and mock-transfected 1205Lu mice. To determine if the reduced bone metastases observed in mice bearing 1205Lu-Smad7 clones was due to reduced expression of TGF-beta target genes known to enhance metastases to bone from breast cancer cells, we analyzed gene expression of osteolytic factors, parathyroid hormone-related protein (PTHrP) and interleukin-11 (IL-11), the chemotactic receptor CXCR4, and osteopontin in 1205Lu cells. Quantitative reverse transcription-PCR analysis indicated that PTHrP, IL-11, CXCR4, and osteopontin mRNA steady-state levels were robustly increased in response to TGF-beta and that Smad7 and the TbetaRI small-molecule inhibitor, SB431542, prevented such induction. In addition, 1205Lu-Smad7 bone metastases expressed significantly lower levels of IL-11, connective tissue growth factor, and PTHrP. These data suggest that TGF-beta promotes osteolytic bone metastases due to melanoma by stimulating the expression of prometastatic factors via the Smad pathway. Blockade of TGF-beta signaling may be an effective treatment for melanoma metastasis to bone. PMID- 17332364 TI - Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib. AB - Somatic mutations within the epidermal growth factor receptor (EGFR) kinase domain are detected in 10% to 30% of human non-small cell lung cancers and are correlated with striking clinical responses in a subset of patients treated with EGFR kinase inhibitors, such as gefitinib and erlotinib. Cell-based studies suggest that these mutant EGFRs promote increased autophosphorylating activity on a subset of EGFR COOH-terminal tyrosines and the consequent engagement of a subset of downstream effectors. Because EGFR function is regulated at multiple levels in vivo, and it is therefore difficult to assess the direct consequences of these mutations on EGFR enzyme function, we measured EGFR catalytic activity in in vitro kinase assays using purified recombinant proteins corresponding to the cytoplasmic domain of wild-type and two frequently detected EGFR mutants (DelL747-P753insS and L858R). Both mutants exhibit substantially increased autophosphorylating activity relative to wild-type EGFR, and they exhibit distinct reaction kinetics. In addition, the mutant kinases are more sensitive to kinase inhibition by gefitinib, which seems to reflect their increased drug affinity. These findings suggest that the altered signaling properties and drug sensitivity of these EGFR mutants that have been observed in vivo largely result from differences in the catalytic properties of the kinase. In addition, we find that the T790M secondary "drug resistance mutation" of EGFR, which frequently arises in relapsed patients that initially responded to treatment, confers enhanced kinase activity to primary activating EGFR alleles and may, therefore, be oncogenic in some contexts. PMID- 17332365 TI - Fractalkine (CX3CL1)- and interleukin-2-enriched neuroblastoma microenvironment induces eradication of metastases mediated by T cells and natural killer cells. AB - Fractalkine (FKN) is a unique CX3C chemokine (CX3CL1) known to induce both adhesion and migration of leukocytes mediated by a membrane-bound and a soluble form, respectively. Its function is mediated through CX3C receptor (CX3CR), which is expressed by T(H)1 immune cells including T cells and natural killer (NK) cells. FKN was shown to be expressed in >90% of 68 neuroblastoma samples as determined by cDNA microarray analysis. Here, we characterized the effect of FKN in the neuroblastoma microenvironment using a syngeneic model genetically engineered to secrete FKN. We show FKN-mediated migration, adhesion, and IFN gamma secretion of immune effector cells, but limited antineuroblastoma activity, in vitro and in vivo. Therefore, we tested the hypothesis that a combined increase of FKN and interleukin-2 (IL-2) in the neuroblastoma microenvironment induces an effective antitumor immune response. For this purpose, IL-2 was targeted to ganglioside GD2, which is highly expressed on neuroblastoma tissue, using an anti-GD2 antibody IL-2 immunocytokine (ch14.18-IL-2). Only mice bearing FKN- and IL-2-enriched neuroblastoma tumors exhibited a reduction in primary tumor growth and a complete eradication of experimental liver metastases. The depletion of T cells and NK cells in vivo abrogated the effect, and these effector cells showed the highest cytolytic activity in vitro. Finally, only the FKN- and IL-2-enriched neuroblastoma microenvironment resulted in T-cell activation and the release of proinflammatory cytokines. In summary, we showed for the first time the immunologic mechanisms by which targeted IL-2 treatment of neuroblastoma with an FKN-rich microenvironment induces an effective antitumor response. PMID- 17332366 TI - Tumor cells expressing anti-CD137 scFv induce a tumor-destructive environment. AB - For immunotherapy to become more effective, there is a need to maximize the antitumor response at the tumor site as well as to eliminate tumor cell variants that lack a given tumor antigen or the ability to present it. We have previously shown that wild-type (WT) cells from the K1735 melanoma (K1735-WT) are rejected following vaccination with cells (K1735-1D8) transfected to express scFv from the anti-CD137 monoclonal antibody 1D8, and that CD4(+) T cells and natural killer (NK) cells are needed for this rejection. We now show that tumors harvested 4 to 10 days after mice had been transplanted with K1735-1D8 cells or a mixture of K1735-1D8 and K1735-WT cells contained more NK cells and that they had an increased percentage of CD4(+) T lymphocytes producing IFNgamma or tumor necrosis factor-alpha. We further show that the percentage of NK cells was higher in B16 1D8 melanomas expressing anti-CD137 scFv than in the WT tumors and that the percentage of FoxP3(+) cells was lower. Admixture of 10% K1735-1D8 cells prevented the progressive growth of transplanted K1735-WT cells in syngeneic mice and also of cells from the antigenically different sarcoma Ag104. Inhibition of WT tumor cells by tumor cells transfected to express anti-CD137 scFv was shown also with the TC1 carcinoma and B16 melanoma. Furthermore, injection of an adenovirus vector, Ad-1D8, which encodes anti-CD137 scFv into established B16 melanomas, significantly prolonged the survival of tumor-bearing mice and could induce regression. Our data suggest that targeting of anti-CD137 scFv to tumors should be explored for therapy for some human cancers. PMID- 17332367 TI - Overexpression of Dicer in precursor lesions of lung adenocarcinoma. AB - Differential microRNA (miR) expression is described in non-small cell lung carcinoma. miR biogenesis requires a set of proteins collectively referred to as the miR machinery. In the proposed multistep carcinogenesis model, peripheral adenocarcinoma of the lung develops from noninvasive precursor lesions known as atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC). The gene array analysis of BAC and adenocarcinoma showed a transient up regulation of Dicer (a key effector protein for small interfering RNA and miR function) and PACT along with down-regulation of most genes encoding miR machinery proteins. Immunohistochemically, Dicer was up-regulated in AAH and BAC and down-regulated in areas of invasion and in advanced adenocarcinoma. A fraction of adenocarcinomas lose Dicer as a result of deletions at the Dicer locus. Expanded immunohistochemical and Western blot analysis showed higher Dicer level in squamous cell carcinoma (SCC) of the lung when compared with adenocarcinoma. Other proteins of the RNA-induced silencing complex (RISC; SND1, PACT, and FXR1) were also present at higher levels in a SCC cell line when compared with an adenocarcinoma cell line. In conclusion, the stoichiometry of miR machinery and RISC depends on histologic subtype of lung carcinoma, varies along the AAH-BAC-adenocarcinoma sequence, and might explain the observed abnormal miR profile in lung cancer. The status of the endogenous miR machinery in various histologic subtypes and stages of lung cancer may help to predict the toxicity of and susceptibility to future RNA interference-based therapy. PMID- 17332368 TI - A novel small-molecule inhibitor of transforming growth factor beta type I receptor kinase (SM16) inhibits murine mesothelioma tumor growth in vivo and prevents tumor recurrence after surgical resection. AB - Malignant mesothelioma is an aggressive and lethal pleural cancer that overexpresses transforming growth factor beta (TGFbeta). We investigated the efficacy of a novel small-molecule TGFbeta type I receptor (ALK5) kinase inhibitor, SM16, in the AB12 syngeneic model of malignant mesothelioma. SM16 inhibited TGFbeta signaling seen as decreased phosphorylated Smad2/3 levels in cultured AB12 cells (IC(50), approximately 200 nmol/L). SM16 penetrated tumor cells in vivo, suppressing tumor phosphorylated Smad2/3 levels for at least 3 h following treatment of tumor-bearing mice with a single i.p. bolus of 20 mg/kg SM16. The growth of established AB12 tumors was significantly inhibited by 5 mg/kg/d SM16 (P < 0.001) delivered via s.c. miniosmotic pumps over 28 days. The efficacy of SM16 was a result of a CD8+ antitumor response because (a) the antitumor effects were markedly diminished in severe combined immunodeficient mice and (b) CD8+ T cells isolated from spleens of mice treated with SM16 showed strong antitumor cytolytic effects whereas CD8+ T cells isolated from spleens of tumor-bearing mice treated with control vehicle showed minimal activity. Treatment of mice bearing large tumors with 5 mg/kg/d SM16 after debulking surgery reduced the extent of tumor recurrence from 80% to <20% (P < 0.05). SM16 was also highly effective in blocking and regressing tumors when given p.o. at doses of 0.45 or 0.65 g/kg in mouse chow. Thus, SM16 shows potent activity against established AB12 malignant mesothelioma tumors using an immune-mediated mechanism and can significantly prevent tumor recurrence after resection of bulky AB12 malignant mesothelioma tumors. These data suggest that ALK5 inhibitors, such as SM16, offer significant potential for the treatment of malignant mesothelioma and possibly other cancers. PMID- 17332369 TI - Estrogen receptors alpha and beta are inhibitory modifiers of Apc-dependent tumorigenesis in the proximal colon of Min/+ mice. AB - Estrogen replacement therapy in postmenopausal women is associated with a reduction in colorectal cancer risk, potentially via interactions between 17beta estradiol (E(2)) and the estrogen receptors (ER) alpha and beta. To study the role of E(2) in intestinal tumor inhibition, we separately crossed C57BL/6J-Min/+ (Min/+) mice with Eralpha(+/-) and Erbeta(+/-) mice to generate ER-deficient Min/+ progeny. We found an increased incidence of visible colon tumors and dysplastic microadenomas in ER-deficient Min/+ relative to Er(+/+)Min/+ controls. Small intestinal tumor numbers were unaffected. Invasive carcinomas were found only in Eralpha(+/-)Min/+ mice, suggesting that ERalpha plays additional non-cell autonomous roles that limit tumor progression. Histologic analyses of ER deficient Min/+ colons, as well as colons from ovariectomized Min/+ mice (OvxMin/+) and E(2)-treated OvxMin/+ mice (OvxMin/+ +E(2)), revealed significant differences in crypt architecture, enterocyte proliferation, and goblet cell differentiation relative to Min/+ and Er(+/+)Apc(+/+) (wild-type) controls. The expression of ERalpha and ERbeta was regionally compartmentalized along the colonic crypt axis, suggesting functional antagonism. Our results indicate that ERalpha and ERbeta are inhibitory modifiers of Apc-dependent colon tumorigenesis. As a result, loss of E(2) and ER signaling in postmenopausal women may contribute to colorectal cancer development. PMID- 17332370 TI - High levels of heat shock protein Hsp72 in cancer cells suppress default senescence pathways. AB - The major heat shock protein Hsp72 is constitutively expressed in many tumor cell lines and biopsies, and its expression correlates with poor prognosis in several types of cancer. Hsp72 was suggested to play an important role in neoplastic transformation and tumor development. We addressed the role of Hsp72 in cancer cells by investigating the consequences of specific depletion of Hsp72 using small interfering RNA. Down-regulation of Hsp72 in certain cancer lines triggered cell senescence associated with activation and stabilization of p53 and induction of the cell cycle inhibitor p21. Effects of Hsp72 depletion on senescence and p53 did not result from a proteotoxic stress, DNA instability, or activation of ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related pathways. Instead, depletion of Hsp72 reduced stability and activity of the p53 inhibitor Hdm2. In addition, Hsp72 depletion triggered a p53-independent senescence program through inhibitory phosphorylation and down-regulation of the cell cycle kinase Cdc2. Therefore, Hsp72 provides a selective advantage to cancer cells by suppressing default senescence via p53-dependent and p53-independent pathways. PMID- 17332371 TI - Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma. AB - Infectious mononucleosis (IM) has been associated with an increased risk of Hodgkin lymphoma (HL), implicating a role for Epstein-Barr virus (EBV) in HL development. Although essential to the understanding of the association, it has remained uncertain if the relationship is restricted to the EBV-positive subset of HL. We collected information on mononucleosis history and childhood socioenvironmental characteristics in a population-based study of 586 patients with classic HL and 3,187 controls in Denmark and Sweden. Tumor EBV status was established for 499 cases by immunohistochemistry and in situ hybridization techniques. Odds ratios (OR) for the relationship between HL risk and mononucleosis and other risk factors were estimated by logistic regression for HL in younger (18-44 years) and older (45-74 years) adults, overall and by tumor EBV status. All analyses were adjusted for country-specific measures of maternal education and mononucleosis history. IM was associated with an increased risk of EBV-positive [OR, 3.23; 95% confidence interval (95% CI) 1.89-5.55] but not EBV negative HL (OR, 1.35; 95% CI, 0.86-2.14). Risk of EBV-positive HL varied with time since IM and was particularly pronounced in younger adults (OR, 3.96; 95% CI, 2.19-7.18). IM-associated lymphomas occurred with a median of 2.9 years (1.8 4.9 years) after infection. The EBV specificity of the IM association was corroborated by a case-case comparison of IM history between younger adult EBV positive and EBV-negative HL patients (OR(IM EBV+ HL versus EBV- HL), 2.68; 95% CI, 1.40-5.12). We found further evidence that IM is associated only with EBV positive HL. This finding is compatible with the notion that EBV-positive and EBV negative HL may have different etiologies. PMID- 17332372 TI - Natural killer dendritic cells are an intermediate of developing dendritic cells. AB - NK dendritic cells (DCs; NKDCs) appear to emerge as a distinct DC subset in humans and rodents, which have the functions of NK cells and DCs. However, the developmental relationship of NKDCs (CD11c(+)NK1.1(+)) to CD11c(+)NK1.1(-) DCs has not been addressed. Herein, we show that NKDCs exist exclusively in the compartment of CD11c(+)MHC II(-) cells in the steady state and express variable levels of DC subset markers, such as the IFN-producing killer DC marker B220, in a tissue-dependent manner. They can differentiate into NK1.1(-) DCs, which is accompanied by the up-regulation of MHC Class II molecules and down-regulation of NK1.1 upon adoptive transfer. However, NK cells (NK(+)CD11c(-)) did not differentiate into NK1.1(+)CD11c(+) cells upon adoptive transfer. Bone marrow derived Ly6C(+) monocytes can be a potential progenitor of NKDCs, as some of them can differentiate into CD11c(+)NK1.1(+) as well as CD11c(+)NK1.1(-) cells in vivo. The steady-state NKDCs have a great capacity to lyse tumor cells but little capability to present antigens. Our studies suggest that NKDCs are an intermediate of developing DCs. These cells appear to bear the unique surface phenotype of CD11c(+)NK1.1(+)MHC II(-) and possess strong cytotoxic function yet show a poor ability to present antigen in the steady state. These findings suggest that NKDCs may play a critical role in linking innate and adaptive immunity. PMID- 17332373 TI - Macrophage biology and immunology: man is not a mouse. PMID- 17332374 TI - Man is not a mouse: reply. PMID- 17332375 TI - CREB-binding protein modulates repeat instability in a Drosophila model for polyQ disease. AB - Although expansion of trinucleotide repeats accounts for over 30 human diseases, mechanisms of repeat instability remain poorly understood. We show that a Drosophila model for the CAG/polyglutamine (polyQ) disease spinocerebellar ataxia type 3 recapitulates key features of human CAG-repeat instability, including large repeat changes and strong expansion bias. Instability is dramatically enhanced by transcription and modulated by nuclear excision repair and a regulator of DNA repair adenosine 3',5'-monophosphate (cAMP) response element binding protein (CREB)-binding protein-a histone acetyltransferase (HAT) whose decreased activity contributes to polyQ disease. Pharmacological treatment to normalize acetylation suppressed instability. Thus, toxic consequences of pathogenic polyQ protein may include enhancing repeat instability. PMID- 17332377 TI - Effect of sedimentation on ice-sheet grounding-line stability. AB - Sedimentation filling space beneath ice shelves helps to stabilize ice sheets against grounding-line retreat in response to a rise in relative sea level of at least several meters. Recent Antarctic changes thus cannot be attributed to sea level rise, strengthening earlier interpretations that warming has driven ice sheet mass loss. Large sea-level rise, such as the approximately 100-meter rise at the end of the last ice age, may overwhelm the stabilizing feedback from sedimentation, but smaller sea-level changes are unlikely to have synchronized the behavior of ice sheets in the past. PMID- 17332376 TI - Asymmetric T lymphocyte division in the initiation of adaptive immune responses. AB - A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity. PMID- 17332378 TI - Discovery of till deposition at the grounding line of Whillans Ice Stream. AB - We report on the discovery of a grounding-line sedimentary wedge ("till delta") deposited by Whillans Ice Stream, West Antarctica. Our observation is that grounding-line deposition serves to thicken the ice and stabilize the position of the grounding line. The ice thickness at the grounding line is greater than that of floating ice in hydrostatic equilibrium. Thus, the grounding line will tend to remain in the same location despite changes in sea level (until sea level rises enough to overcome the excess thickness that is due to the wedge). Further, our observation demonstrates the occurrence of rapid subglacial erosion, sediment transport by distributed subglacial till deformation, and grounding-line sedimentation, which have important implications for ice dynamics, numerical modeling of ice flow, and interpretation of the sedimentation record. PMID- 17332379 TI - Animal health research. PMID- 17332380 TI - Cancer research. Tight budget takes a toll on U.S.-funded clinical trials. PMID- 17332381 TI - Particle physics. Dreams collide with reality for international experiment. PMID- 17332383 TI - Archaeology. Mystery towers in Peru are an ancient solar calendar. PMID- 17332382 TI - Zoology. African penguin populations reported in a puzzling decline. PMID- 17332384 TI - U.S. innovation. Democrats rescue technology research program. PMID- 17332385 TI - Stem cells. Data on Adult stem cells questioned. PMID- 17332386 TI - Neuroanatomy. Brain evolution studies go micro. PMID- 17332387 TI - Oncology. Recruiting the cell's own guardian for cancer therapy. PMID- 17332388 TI - Skin biology. A healthy tan? PMID- 17332389 TI - Skin biology. Why I have red hair, need to avoid the sun, and shouldn't commit a crime. PMID- 17332390 TI - Climate change. Pollutant hazes extend their climate-changing reach. PMID- 17332392 TI - Online versus hardcopy textbooks. PMID- 17332391 TI - To sleep, perchance to dream. PMID- 17332393 TI - Is the EC afraid of its own visions? PMID- 17332394 TI - Comment on "Detecting awareness in the vegetative state". AB - In a report of a single patient in a persistent vegetative state, Owen et al. (Brevia, 8 September 2006, p. 1402) claimed that the presence of task-specific brain activation in response to verbal command implies both covert conscious awareness and a capacity for intention. We argue that neither can be securely inferred from the evidence presented. PMID- 17332395 TI - Comment on "Detecting awareness in the vegetative state". AB - Owen et al. (Brevia, 8 September 2006, p. 1402) claimed that a patient's brain activity revealed that she was consciously responding to commands despite being in a vegetative state. However, several alternative explanations were not eliminated. Specifically, the activity could reflect unconscious reactions to the last word in the command, not conscious decisions to respond. A refined experimental design could clarify these issues. PMID- 17332396 TI - Nuclear war. Consequences of regional-scale nuclear conflicts. PMID- 17332397 TI - Physics. Negative refraction for electrons? PMID- 17332398 TI - Epidemiology. Keep it local. PMID- 17332399 TI - Chemistry. Water from first principles. PMID- 17332400 TI - Biochemistry. A missing link in membrane protein evolution. PMID- 17332401 TI - Ecology. How the wood moves. PMID- 17332402 TI - Atmosphere. Forecasting hurricane intensity and impacts. PMID- 17332403 TI - Was there really an Archean phosphate crisis? AB - During the Archean, massive amounts of iron were deposited in the form of banded iron formations. It has been suggested that sedimenting particles of ferric oxyhydroxide may have stripped dissolved phosphate from the oceans, causing a reduction in phytoplankton productivity. However, that model does not take into account the high concentration of dissolved silica that was present in seawater at that time. We show experimentally that silica effectively competes with phosphate for sorption sites on ferrihydrite particles. Furthermore, coprecipitation of silica with ferrihydrite reduces particle reactivity toward phosphate. Hence, Archean oceans probably contained considerably more phosphate than previously predicted. PMID- 17332404 TI - Hurricane intensity and eyewall replacement. AB - Observations made during the historic 2005 hurricane season document a case of "eyewall replacement." Clouds outside the hurricane eyewall coalesce to form a new eyewall at a greater radius from the storm center, and the old eyewall dies. The winds in the new eyewall are initially weaker than those in the original eyewall, but as the new eyewall contracts, the storm reintensifies. Understanding this replacement mechanism is vital to forecasting variations in hurricane intensity. Processes in the "moat" region between the new and old eyewall have been particularly unclear. Aircraft data now show that the moat becomes dynamically similar to the eye and thus is converted into a region inimical to survival of the inner eyewall. We suggest that targeting aircraft to key parts of the storm to gain crucial input to high-resolution numerical models can lead to improvements in forecasting hurricane intensity. PMID- 17332405 TI - Chankillo: a 2300-year-old solar observatory in coastal Peru. AB - The Thirteen Towers of Chankillo run north to south along a low ridge within a fourth-century B.C.E. ceremonial complex in north coastal Peru. From evident observing points within the adjacent buildings to the west and east, they formed an artificial toothed horizon that spanned-almost exactly-the annual rising and setting arcs of the Sun. The Chankillo towers thus provide evidence of early solar horizon observations and of the existence of sophisticated Sun cults, preceding the Sun pillars of Incaic Cusco by almost two millennia. PMID- 17332406 TI - Predictions of the properties of water from first principles. AB - A force field for water has been developed entirely from first principles, without any fitting to experimental data. It contains both pairwise and many-body interactions. This force field predicts the properties of the water dimer and of liquid water in excellent agreement with experiments, a previously elusive objective. Precise knowledge of the intermolecular interactions in water will facilitate a better understanding of this ubiquitous substance. PMID- 17332407 TI - The focusing of electron flow and a Veselago lens in graphene p-n junctions. AB - The focusing of electric current by a single p-n junction in graphene is theoretically predicted. Precise focusing may be achieved by fine-tuning the densities of carriers on the n- and p-sides of the junction to equal values. This finding may be useful for the engineering of electronic lenses and focused beam splitters using gate-controlled n-p-n junctions in graphene-based transistors. PMID- 17332408 TI - Halwaxiids and the early evolution of the lophotrochozoans. AB - Halkieriids and wiwaxiids are cosmopolitan sclerite-bearing metazoans from the Lower and Middle Cambrian. Although they have similar scleritomes, their phylogenetic position is contested. A new scleritomous fossil from the Burgess Shale has the prominent anterior shell of the halkieriids but also bears wiwaxiid like sclerites. This new fossil defines the monophyletic halwaxiids and indicates that they have a key place in early lophotrochozoan history. PMID- 17332409 TI - Rethinking organic aerosols: semivolatile emissions and photochemical aging. AB - Most primary organic-particulate emissions are semivolatile; thus, they partially evaporate with atmospheric dilution, creating substantial amounts of low volatility gas-phase material. Laboratory experiments show that photo-oxidation of diesel emissions rapidly generates organic aerosol, greatly exceeding the contribution from known secondary organic-aerosol precursors. We attribute this unexplained secondary organic-aerosol production to the oxidation of low volatility gas-phase species. Accounting for partitioning and photochemical processing of primary emissions creates a more regionally distributed aerosol and brings model predictions into better agreement with observations. Controlling organic particulate-matter concentrations will require substantial changes in the approaches that are currently used to measure and regulate emissions. PMID- 17332410 TI - Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit. AB - Long-term potentiation (LTP), which approximates Hebb's postulate of associative learning, typically requires depolarization-dependent glutamate receptors of the NMDA (N-methyl-D-aspartate) subtype. However, in some neurons, LTP depends instead on calcium-permeable AMPA-type receptors. This is paradoxical because intracellular polyamines block such receptors during depolarization. We report that LTP at synapses on hippocampal interneurons mediating feedback inhibition is "anti-Hebbian":Itis induced by presynaptic activity but prevented by postsynaptic depolarization. Anti-Hebbian LTP may occur in interneurons that are silent during periods of intense pyramidal cell firing, such as sharp waves, and lead to their altered activation during theta activity. PMID- 17332411 TI - Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. AB - Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences. PMID- 17332412 TI - Reconstitution of DNA segregation driven by assembly of a prokaryotic actin homolog. AB - Multiple unrelated polymer systems have evolved to partition DNA molecules between daughter cells at division. To better understand polymer-driven DNA segregation, we reconstituted the three-component segregation system of the R1 plasmid from purified components. We found that the ParR/parC complex can construct a simple bipolar spindle by binding the ends of ParM filaments, inhibiting dynamic instability, and acting as a ratchet permitting incorporation of new monomers and riding on the elongating filament ends. Under steady-state conditions, the dynamic instability of unattached ParM filaments provides the energy required to drive DNA segregation. PMID- 17332413 TI - Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity. AB - IKKepsilon is an IKK (inhibitor of nuclear factor kappaBkinase)-related kinase implicated in virus induction of interferon-beta (IFNbeta). We report that, although mice lacking IKKepsilon produce normal amounts of IFNbeta, they are hypersusceptible to viral infection because of a defect in the IFN signaling pathway. Specifically, a subset of type I IFN-stimulated genes are not activated in the absence of IKKepsilon because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKKepsilon is activated by IFNbeta and that IKKepsilon directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKKepsilon plays a critical role in the IFN inducible antiviral transcriptional response. PMID- 17332414 TI - LRP6 mutation in a family with early coronary disease and metabolic risk factors. AB - Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors. PMID- 17332415 TI - Local interactions select for lower pathogen infectivity. AB - Theory suggests that the current rapid increase in connectivity and consequential changes in the structure of human, agricultural, and wildlife populations may select for parasite strains with higher infectivity. We carried out a test of this spatial theory by experimentally altering individual host movement rates in a model host/pathogen system by altering the viscosity of their environment. In our microevolutionary selection experiments, the infectivity of the virus was, as predicted by the theory, reduced in the most viscous populations. We therefore provide empirical support for the theory that population structure affects the evolution of infectious organisms. PMID- 17332416 TI - As time goes by: temporal constraints on emotional activation of inferior medial prefrontal cortex. AB - To investigate the influence of stimulus duration on emotional processing, we measured changes of regional cerebral blood flow (rCBF) in 14 healthy subjects who viewed neutral or emotional images presented for 3 or 6 s. Presentation for 3 s reproduced the previous result of higher rCBF in inferior medial prefrontal cortex (IMPC) during neutral than emotional stimulation. Six-second presentation reverted this relationship, with activity in IMPC being higher during emotional stimulation. Prolonged stimulus presentation attenuated the rise of rCBF associated with emotions in left parietal cortex and cerebellar hemisphere. We speculate that the different rCBF during neutral and emotional stimulation for 6 s is a consequence of attention divided between the emotional stimuli and their associations. Thus, prefrontal activity rises when a cognitive task accompanies emotional stimulation because several cognitive processes compete for attention. The IMPC may serve the mechanism of attention underlying the concept of a default mode of brain function, selecting among competitive inputs from multiple brain regions rather than just processing emotions. The results emphasize the importance of implicit cognitive processing during emotional activation, however, unintended. PMID- 17332417 TI - Involvement of polyamines in the drought resistance of rice. AB - This study investigated whether and how polyamines (PAs) in rice (Oryza sativa L.) plants are involved in drought resistance. Six rice cultivars differing in drought resistance were used and subjected to well-watered and water-stressed treatments during their reproductive period. The activities of arginine decarboxylase, S-adenosyl-L-methionine decarboxylase, and spermidine (Spd) synthase in the leaves were significantly enhanced by water stress, in good agreement with the increase in putrescine (Put), Spd, and spermine (Spm) contents there. The increased contents of free Spd, free Spm, and insoluble-conjugated Put under water stress were significantly correlated with the yield maintenance ratio (the ratio of grain yield under water-stressed conditions to grain yield under well-watered conditions) of the cultivars. Free Put at an early stage of water stress positively, whereas at a later stage negatively, correlated with the yield maintenance ratio. No significant differences were observed in soluble-conjugated PAs and insoluble-conjugated Spd and Spm among the cultivars. Free PAs showed significant accumulation when leaf water potentials reached -0.51 MPa to -0.62 MPa for the drought-resistant cultivars and -0.70 MPa to -0.84 MPa for the drought-susceptible ones. The results suggest that rice has a large capacity to enhance PA biosynthesis in leaves in response to water stress. The role of PAs in plant defence to water stress varies with PA forms and stress stages. In adapting to drought it would be good for rice to have the physiological traits of higher levels of free Spd/free Spm and insoluble-conjugated Put, as well as early accumulation of free PAs, under water stress. PMID- 17332418 TI - Adenosine 5'-phosphosulphate reductase is regulated differently in Allium cepa L. and Brassica oleracea L. upon exposure to H2S. AB - The reduction of adenosine 5'-phosphosulphate (APS) by APS reductase (APR) is considered to be one of the rate-limiting steps in the assimilation of sulphur in plants. In order to identify the mechanisms of regulation of this enzyme, the impact of atmospheric H2S exposure on mRNA expression, protein level, and activity of APR was studied in two species (Allium cepa L. and Brassica oleracea L.) with different physiological responses to H2S exposure. As expected, H2S exposure resulted in a rapid increase in thiol compounds in the shoot of both species. There was a substantial increase in total sulphur content in shoots of A. cepa, whereas it was hardly affected or even slightly decreased in B. oleracea. Sulphate uptake was only marginally affected in A. cepa, whereas it was strongly decreased in B. oleracea upon H2S exposure. Furthermore, H2S exposure resulted in a down-regulation of APR activity in shoot and roots of both species, which was probably mediated by a transcriptional mechanism of regulation by thiols, since mRNA levels also decreased. However, in contrast to B. oleracea, APR protein level was not affected by H2S exposure in A. cepa. The reduction in APR activity in onion was therefore achieved by an additional as yet unknown post translational regulation. These results demonstrate that not only the physiological response to H2S, but also the molecular mechanisms of regulation of APR differ in the two species. PMID- 17332420 TI - Juvenile metachromatic leukodystrophy: understanding the disease and implications for nursing care. AB - Hematopoietic stem cell transplants are increasingly being performed in attempt to halt the progression of juvenile metachromatic leukodystrophy, which is a rare neurodegenerative disease. Children who are diagnosed with metachromatic leukodystrophy are not commonly cared for by nurses who specialize in pediatric stem cell transplants. This article provides nurses with insight about this disease and serves as a guide for nursing care of this patient population during hematopoietic stem cell transplant. The case study highlights the complexities of care of this population while illustrating many of the unique care needs of patients with metachromatic leukodystrophy undergoing hematopoietic stem cell transplant. The article provides information about the pathophysiology of metachromatic leukodystrophy, the natural progression of symptoms, and how hematopoietic stem cell transplant may work to halt the progression of juvenile metachromatic leukodystrophy. It also focuses on the implications of nursing care, including a review of systems, the need for increased patient and family education, and the complexities of caring for a family with multiple affected children. PMID- 17332421 TI - Delayed vomiting in children with cancer after receiving moderately high or highly emetogenic chemotherapy. AB - Delayed vomiting is a potentially significant adverse effect of chemotherapy used to treat childhood cancer, but little is known about the experience of delayed vomiting in children and adolescents. An exploratory study was conducted to determine the pattern of delayed vomiting in children and adolescents with cancer after highly emetic chemotherapy and to identify possible risk factors. In a sample of 82 children and adolescents who completed 117 cycles of highly emetic chemotherapy, the overall prevalence of delayed vomiting was 32%. The frequency of delayed vomiting was highest on delayed day 2, with 21% of participants experiencing vomiting. By delayed day 7, only 9% of participants still reported vomiting. The severity of vomiting was moderate to severe in 11% to 12% of subjects. Age and gender had no significant effect on delayed vomiting. The emetic potential of the agent, incomplete protection from acute vomiting, and treatment regimens that lasted 6 or more days significantly affected delayed vomiting. In addition, a history of motion sickness, lack of acute control, and 6 or more days of chemotherapy were predictive of delayed vomiting. PMID- 17332422 TI - A systematic review of nonpharmacologic adjunctive therapies for symptom management in children with cancer. AB - Symptom management in pediatric oncology remains a problem. Despite remarkable pharmacologic and surgical advances, children continue to report symptoms as the most troublesome aspect of cancer treatment. However, there are additional therapies that are not considered standard symptom management, such as acupuncture and guided imagery. These nonpharmacologic adjunctive therapies are a potential source of assistance for children with unrelenting pain, nausea, or other unpleasant symptoms due to cancer treatment. This article summarizes research studies that have examined nonpharmacologic therapies for symptom management in pediatric oncology. PMID- 17332423 TI - Pediatric brain tumor patients: their parents' perceptions of the hospital experience. AB - Studies have shown that admission to the hospital of a child can induce feelings of fear and helplessness in parents, challenging usual patterns of coping and parenting competence. Stress has been associated with parents' need to establish effective communication with staff and their need for information, ready access to their children, and participation in decision making relating to their child's care. This study of coping and adjustment was undertaken with the parents, including mothers and fathers, of children under 18 years of age diagnosed with a brain tumor, presenting at Royal Children's Hospital, Melbourne, between 2001 and 2002 (N=53). It was a prospective study using repeated measures over time. Participants in the study were involved in a questionnaire interview at 4 different points: at the time of diagnosis, 6 months postdiagnosis, 1 year postdiagnosis, and 2 years postdiagnosis, in which they were asked, among other things, about their experience of the hospital. The point of diagnosis was marked by a high level of dependence, with parents coping with rapid decision making and shock, and the surrender of care of their child. Parents identified high levels of information need but noted that they were often too stressed to take in information early on, and that this information need persisted up to the 2-year postdiagnosis point. More parents expressed dissatisfaction with the hospital and particularly with their interactions with the health care team at the 6-month post-diagnosis period, reflecting a possible reduction in attention given to families once they had settled into the treatment routine and the crisis of diagnosis had passed. PMID- 17332424 TI - Health-related quality of life following hematopoietic stem cell transplant during childhood. AB - The purpose of this study is to examine the self-reported and parent-reported health-related quality of life (HRQoL) of children (age<19 years) who received a hematopoietic (bone marrow, cord blood, or peripheral blood) stem cell transplant (SCT) at the University of Nebraska Medical Center (UNMC). A total of 35 families participated: 31 SCT recipients, 35 mothers, and 28 fathers. Mean scores were 73.6 child, 71.2 mothers, and 76.2 fathers (range of 0-100, with high scores indicating better HRQoL). No significant overall HRQoL difference between parent and child were reported. Mothers reported significantly lower physical functioning (F2,23=3.509, P=.041) compared to child (P=.041) and fathers (P=.025). Older age at time of transplant was associated with higher procedural anxiety according to child (r=.498, P=.005) and mothers (r=.466, P=.008). Older age at time of transplant was associated with less worry according to fathers (r= .589, P=.002). Overall, SCT recipients and their parents report moderately high HRQoL. PMID- 17332425 TI - CHF1/Hey2 plays a pivotal role in left ventricular maturation through suppression of ectopic atrial gene expression. AB - We previously reported that mice lacking the hairy-related basic helix-loop-helix (bHLH) transcription factor CHF1/Hey2 develop a thin-walled left ventricle. To explore the basis for this phenotype, we examined regional gene expression patterns in the developing myocardium. We found that atrial natriuretic factor (ANF), which is normally expressed in the atria and trabeculae and is restricted from the developing compact myocardium beginning at embryonic day 13.5, is persistently expressed in the left ventricular compact myocardium of the knockout animals. We also examined the expression pattern of the T-box transcription factor Tbx5, a known regulator of ANF, and an additional Tbx5-dependent gene, connexin 40 (Cx40), both of which share a similar expression pattern to ANF during development. Tbx5 and Cx40 were similarly expressed ectopically in the compact myocardium of the CHF1/Hey2 knockout mouse. The atrial contractile genes mlc1a and mlc2a were also expressed ectopically in the left ventricular compact myocardium, providing evidence for a general dysregulation of atrial gene expression. Crossing of a myocardial-specific CHF1/Hey2 transgenic mouse with the knockouts led to rescue of the thin-walled myocardial phenotype and restoration of the normal patterns of gene expression. Myocardial cell proliferation, which has been shown previously to be suppressed by Tbx5, was also decreased in the knockout mice and rescued by the transgene. Our findings suggest that CHF1/Hey2 suppresses atrial identity in the left ventricular compact myocardium, facilitates myocardial proliferation by suppressing Tbx5, and thereby promotes proper ventricular myocardial maturation. PMID- 17332426 TI - Tetralogy of fallot and alterations in vascular endothelial growth factor-A signaling and notch signaling in mouse embryos solely expressing the VEGF120 isoform. AB - The importance of vascular endothelial growth factor-A (VEGF) and subsequent Notch signaling in cardiac outflow tract development is generally recognized. Although genetic heterogeneity and mutations of these genes in both humans and mouse models relate to a high susceptibility to develop outflow tract malformations such as tetralogy of Fallot and peripheral pulmonary stenosis, no etiology has been proposed so far. Using immunohistochemistry, in situ hybridization, and quantitative RT-PCR on embryonic hearts, we have shown spatiotemporal increase and abnormal patterning of Vegf/VEGF/(phosphorylated) VEGFR-2, (cleaved) Notch1, and Jagged2 in the outflow tract of Vegf120/120 mouse embryos. This coincides with hyperplasia of specifically the outflow tract cushions and a high degree of subpulmonary myocardial apoptosis that, in later stages, manifest as pulmonary stenosis and ventricular septal defects. We postulate that increase of VEGF and Notch signaling during right ventricular outflow tract development can lead to abnormal development of both cushion and myocardial structures. Defective right ventricular outflow tract development as presented provides new insight in the etiology of tetralogy of Fallot. PMID- 17332427 TI - Genetic dissection of a blood pressure quantitative trait locus on rat chromosome 1 and gene expression analysis identifies SPON1 as a novel candidate hypertension gene. AB - A region with a major effect on blood pressure (BP) is located on rat chromosome 1. We have previously isolated this region in reciprocal congenic strains (WKY.SHR-Sa and SHR.WKY-Sa) derived from a cross of the spontaneously hypertensive rat (SHR) with the Wistar-Kyoto rat (WKY) and shown that there are 2 distinct BP quantitative trait loci, BP1 and BP2, in this region. Sisa1, a congenic substrain from the SHR.WKY-Sa animals carrying an introgressed segment of 4.3Mb, contains BP1. Here, we report further dissection of BP1 by the creation of 2 new mutually exclusive congenic substrains (Sisa1a and Sisa1b) and interrogation of candidate genes by expression profiling and targeted transcript sequencing. Only 1 of the substrains (Sisa1a) continued to demonstrate a BP difference but with a reduced introgressed segment of 3Mb. Exonic sequencing of the 20 genes located in the Sisa1a region did not identify any major differences between SHR and WKY. However, microarray expression profiling of whole kidney samples and subsequent quantitative RT-PCR identified a single gene, Spon1 that exhibited significant differential expression between the WKY and SHR genotypes at both 6 and 24 weeks of age. Western blot analysis confirmed an increased level of the Spon1 gene product in SHR kidneys. Spon1 belongs to a family of genes with antiangiogenic properties. These findings justify further investigation of this novel positional candidate gene in BP control in hypertensive rat models and humans. PMID- 17332428 TI - Cardiomyocyte degeneration with calpain deficiency reveals a critical role in protein homeostasis. AB - Regulating the balance between synthesis and proteasomal degradation of cellular proteins is essential for tissue growth and maintenance, but the critical pathways regulating protein ubiquitination and degradation are incompletely defined. Although participation of calpain calcium-activated proteases in post necrotic myocardial autolysis is well characterized, their importance in homeostatic turnover of normal cardiac tissue is controversial. Hence, we evaluated the consequences of physiologic calpain (calcium-activated protease) activity in cultured cardiomyocytes and unstressed mouse hearts. Comparison of in vitro proteolytic activities of cardiac-expressed calpains 1 and 2 revealed calpain 1, but not calpain 2, activity at physiological calcium concentrations. Physiological calpain 1 activation was evident in adenoviral transfected cultured cardiomyocytes as proteolysis of specific substrates, generally increased protein ubiquitination, and accelerated protein turnover, that were each inhibited by coexpression of the inhibitor protein calpastatin. Conditional forced expression of calpain 1, but not calpain 2, in mouse hearts demonstrated substrate-specific proteolytic activity under basal conditions, with hyperubiquitination of cardiac proteins and increased 26S proteasome activity. Loss of myocardial calpain activity by forced expression of calpastatin diminished ubiquitination of 1 or more specific myocardial proteins, without affecting overall ubiquitination or proteasome activity, and resulted in a progressive dilated cardiomyopathy characterized by accumulation of intracellular protein aggregates, formation of autophagosomes, and degeneration of sarcomeres. Thus, calpain 1 is upstream of, and necessary for, ubiquitination and proteasomal degradation of a subset of myocardial proteins whose abnormal accumulation produces autophagosomes and degeneration of cardiomyocytes with functional decompensation. PMID- 17332429 TI - Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. AB - Autophagy is an intracellular bulk degradation process for proteins and organelles. In the heart, autophagy is stimulated by myocardial ischemia. However, the causative role of autophagy in the survival of cardiac myocytes and the underlying signaling mechanisms are poorly understood. Glucose deprivation (GD), which mimics myocardial ischemia, induces autophagy in cultured cardiac myocytes. Survival of cardiac myocytes was decreased by 3-methyladenine, an inhibitor of autophagy, suggesting that autophagy is protective against GD in cardiac myocytes. GD-induced autophagy coincided with activation of AMP-activated protein kinase (AMPK) and inactivation of mTOR (mammalian target of rapamycin). Inhibition of AMPK by adenine 9-beta-d-arabinofuranoside or dominant negative AMPK significantly reduced GD-induced autophagy, whereas stimulation of autophagy by rapamycin failed to cause an additive effect on GD-induced autophagy, suggesting that activation of AMPK and inhibition of mTOR mediate GD-induced autophagy. Autophagy was also induced by ischemia and further enhanced by reperfusion in the mouse heart, in vivo. Autophagy resulting from ischemia was accompanied by activation of AMPK and was inhibited by dominant negative AMPK. In contrast, autophagy during reperfusion was accompanied by upregulation of Beclin 1 but not by activation of AMPK. Induction of autophagy and cardiac injury during the reperfusion phase was significantly attenuated in beclin 1(+/-) mice. These results suggest that, in the heart, ischemia stimulates autophagy through an AMPK dependent mechanism, whereas ischemia/reperfusion stimulates autophagy through a Beclin 1-dependent but AMPK-independent mechanism. Furthermore, autophagy plays distinct roles during ischemia and reperfusion: autophagy may be protective during ischemia, whereas it may be detrimental during reperfusion. PMID- 17332430 TI - Rho kinase-mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats. AB - Vascular remodeling, rather than vasoconstriction, is believed to account for high vascular resistance in severe pulmonary arterial hypertension (PAH). We have found previously that acute Rho kinase inhibition nearly normalizes PAH in chronically hypoxic rats that have no occlusive neointimal lesions. Here we examined whether Rho kinase-mediated vasoconstriction was also important in a rat model of severe occlusive PAH. Adult rats were exposed to chronic hypoxia ( approximately 10% O(2)) after subcutaneous injection of the vascular endothelial growth factor receptor inhibitor SUGEN 5416. Hemodynamic measurements were made in anesthetized rats after 2 weeks of hypoxia (early group) and 3 weeks of hypoxia plus 2 weeks of normoxia (late group). Both groups developed PAH, with greater severity in the late group. In the early group, intravenous fasudil was more effective than intravenous bradykinin, inhaled NO, or intravenous iloprost in reducing right ventricular systolic pressure. Despite more occlusive vascular lesions, fasudil also markedly reduced right ventricular systolic pressure in late-stage rats. Blood-perfused lungs from late-stage rats showed spontaneous vasoconstriction, which was reversed partially by the endothelin A receptor blocker BQ123 and completely by fasudil or Y-27632. Phosphorylation of MYPT1, a downstream target of Rho kinase, was increased in lungs from both groups of rats, and fasudil (intravenous) reversed the increased phosphorylation in the late group. Thus, in addition to structural occlusion, Rho kinase-mediated vasoconstriction is an important component of severe PAH in SUGEN 5416/hypoxia exposed rats, and PAH can be significantly reduced in the setting of a severely remodeled lung circulation if an unconventional vasodilator is used. PMID- 17332431 TI - Critical role of the NAD(P)H oxidase subunit p47phox for left ventricular remodeling/dysfunction and survival after myocardial infarction. AB - Accumulating evidence suggests a critical role of increased reactive oxygen species production for left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). An increased myocardial activity of the NAD(P)H oxidase, a major oxidant enzyme system, has been observed in human heart failure; however, the role of the NAD(P)H oxidase for LV remodeling and dysfunction after MI remains to be determined. MI was induced in wild-type (WT) mice (n=46) and mice lacking the cytosolic NAD(P)H oxidase component p47(phox) (p47(phox)-/- mice) (n=32). Infarct size was similar among the groups. NAD(P)H oxidase activity was markedly increased in remote LV myocardium of WT mice after MI as compared with sham-operated mice (83+/-8 versus 16.7+/-3.5 nmol of O(2)(-) x microg(-1) x min(-1); P<0.01) but not in p47(phox)-/- mice after MI (13.5+/-3.6 versus 15.5+/ 3.5 nmol of O(2)(-) x microg(-1) x min(-1)), as assessed by electron-spin resonance spectroscopy using the spin probe CP-H. Furthermore, increased myocardial xanthine oxidase activity was observed in WT, but not in p47(phox)-/- mice after MI, suggesting NAD(P)H oxidase-dependent xanthine oxidase activation. Myocardial reactive oxygen species production was increased in WT mice, but not in p47(phox)-/- mice, after MI. LV cavity dilatation and dysfunction 4 weeks after MI were markedly attenuated in p47(phox)-/- mice as compared with WT mice, as assessed by echocardiography (LV end-diastolic diameter: 4.5+/-0.2 versus 6.3+/-0.3 mm, P<0.01; LV ejection fraction, 35.8+/-2.5 versus 22.6+/-4.4%, P<0.05). Furthermore, cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis were substantially reduced in p47(phox)-/- mice as compared with WT mice. Importantly, the survival rate was markedly higher in p47(phox)-/- mice as compared with WT mice after MI (72% versus 48%; P<0.05). These results suggest a pivotal role of NAD(P)H oxidase activation and its subunit p47(phox) for LV remodeling/dysfunction and survival after MI. The NAD(P)H oxidase system represents therefore a potential novel therapeutic target to prevent cardiac failure after MI. PMID- 17332432 TI - VEGF165 gene-mediated arteriogenesis and cardioprotection in large mammals with acute myocardial infarction. Confirmation of previous results from other authors. PMID- 17332433 TI - Big cells, little cells, stem cells: agents of cardiac plasticity. PMID- 17332434 TI - Preconditioning stem cells for cardiovascular disease: an important step forward. PMID- 17332435 TI - G protein-coupled receptor G2A: friend or foe of the vasculature? PMID- 17332436 TI - Developmental programming through epigenetic changes. PMID- 17332437 TI - Mitochondrial dysfunction in atherosclerosis. AB - Increased production of reactive oxygen species in mitochondria, accumulation of mitochondrial DNA damage, and progressive respiratory chain dysfunction are associated with atherosclerosis or cardiomyopathy in human investigations and animal models of oxidative stress. Moreover, major precursors of atherosclerosis hypercholesterolemia, hyperglycemia, hypertriglyceridemia, and even the process of aging-all induce mitochondrial dysfunction. Chronic overproduction of mitochondrial reactive oxygen species leads to destruction of pancreatic beta cells, increased oxidation of low-density lipoprotein and dysfunction of endothelial cells-factors that promote atherosclerosis. An additional mechanism by which impaired mitochondrial integrity predisposes to clinical manifestations of vascular diseases relates to vascular cell growth. Mitochondrial function is required for normal vascular cell growth and function. Mitochondrial dysfunction can result in apoptosis, favoring plaque rupture. Subclinical episodes of plaque rupture accelerate the progression of hemodynamically significant atherosclerotic lesions. Flow-limiting plaque rupture can result in myocardial infarction, stroke, and ischemic/reperfusion damage. Much of what is known on reactive oxygen species generation and modulation comes from studies in cultured cells and animal models. In this review, we have focused on linking this large body of literature to the clinical syndromes that predispose humans to atherosclerosis and its complications. PMID- 17332438 TI - AMP-activated protein kinase in the heart: role during health and disease. AB - AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that is expressed in most mammalian tissues including cardiac muscle. Among the multiple biological processes influenced by AMPK, regulation of fuel supply and energy-generating pathways in response to the metabolic needs of the organism is fundamental and likely accounts for the remarkable evolutionary conservation of this enzyme complex. By regulating the activity of acetyl-coenzyme A carboxylase, AMPK affects levels of malonyl-coenzyme A, a key energy regulator in the cell. AMPK is generally quiescent under normal conditions but is activated in response to hormonal signals and stresses sufficient to produce an increase in AMP/ATP ratio, such as hypoglycemia, strenuous exercise, anoxia, and ischemia. Once active, muscle AMPK enhances uptake and oxidative metabolism of fatty acids as well as increases glucose transport and glycolysis. Data from AMPK deficiency models suggest that AMPK activity might influence the pathophysiology and therapy of diabetes and increase heart tolerance to ischemia. Effects that are not as well understood include AMPK regulation of transcription. Different AMPK isoforms are found in distinct locations within the cell and have distinct functions in different tissues. A principal mode of AMPK activation is phosphorylation by upstream kinases (eg, LKB1). These kinases have a fundamental role in cell-cycle regulation and protein synthesis, suggesting involvement in a number of human disorders including cardiac hypertrophy, apoptosis, cancer, and atherosclerosis. The physiological role played by AMPK during health and disease is far from being clearly defined. Naturally occurring mutations affecting the nucleotide-sensing modules in the regulatory gamma subunit of AMPK lead to enzyme dysregulation and inappropriate activation under resting conditions. Glycogen accumulation ensues, leading to human disease manifesting as cardiac hypertrophy, accessory atrioventricular connections, and degeneration of the physiological conduction system. Whether AMPK is a key participant or bystander in other disease states and whether its selective manipulation may significantly benefit these conditions remain important questions. PMID- 17332440 TI - Intracellular signaling mechanisms regulating toll-like receptor-mediated activation of eosinophils. AB - Activation of eosinophils by microbe-derived molecules via Toll-like receptors (TLR) potentially provides the link between microbe-induced innate immune responses and the exacerbation of allergic inflammation. We investigated the expression of TLRs and the effect of their ligands on human eosinophils. Expression of TLR1-9 was detected by Western blot and flow cytometry. Adhesion molecules, cytokines, superoxides, and eosinophlilic cationic protein (ECP) were assessed by flow cytometry, enzyme-linked immunosorbent assay, chemiluminescent method, and fluorescence immunoassay, respectively. Human eosinophils differentially expressed TLR1, -2, -4, -5, -6, -7, and -9. Peptidoglycan (PGN) (TLR2 ligand), flagellin (TLR5 ligand), and Imiquimod R837 (TLR7 ligand) could significantly upregulate cell surface expression of intercellular adhesion molecule (ICAM)-1 and CD18, and induce the release of IL-1beta, IL-6, IL-8, growth-related oncogene (GRO)-alpha, and superoxides of eosinophils. Only PGN could induce the degranulation for ECP release. However, ds poly I-C (TLR3 ligand), LPS (TLR4 ligand), ssRNA (TLR8 ligand), and CpG-DNA (TLR9 ligand) were much less effective or inactive. PGN, flagellin, and R837 could activate both nuclear factor (NF)-kappaB and extracellular signal-regulated protein kinase (ERK). PGN could activate phosphatidylinositol 3-kinase (PI3K)-Akt, and R837 both PI3K-Akt and p38 mitogen-activated protein kinase (MAPK). The induction of the release of IL-1beta, IL-6, IL-8, GRO-alpha, superoxides, and ECP by PGN, flagellin, and R837 was found to be differentially regulated by NF-kappaB, ERK, PI3K-Akt, and p38 MAPK. The above results therefore support that microbial infection may lead to the exacerbation of allergic inflammation. PMID- 17332439 TI - Regulation of phosphodiesterase 3 and inducible cAMP early repressor in the heart. AB - Growing evidence suggests that multiple spatially, temporally, and functionally distinct pools of cyclic nucleotides exist and regulate cardiac performance, from acute myocardial contractility to chronic gene expression and cardiac structural remodeling. Cyclic nucleotide phosphodiesterases (PDEs), by hydrolyzing cAMP and cyclic GMP, regulate the amplitude, duration, and compartmentation of cyclic nucleotide-mediated signaling. In particular, PDE3 enzymes play a major role in regulating cAMP metabolism in the cardiovascular system. PDE3 inhibitors, by raising cAMP content, have acute inotropic and vasodilatory effects in treating congestive heart failure but have increased mortality in long-term therapy. PDE3A expression is downregulated in human and animal failing hearts. In vitro, inhibition of PDE3A function is associated with myocyte apoptosis through sustained induction of a transcriptional repressor ICER (inducible cAMP early repressor) and thereby inhibition of antiapoptotic molecule Bcl-2 expression. Sustained induction of ICER may also cause the change of other protein expression implicated in human and animal failing hearts. These data suggest that the downregulation of PDE3A observed in failing hearts may play a causative role in the progression of heart failure, in part, by inducing ICER and promoting cardiac myocyte dysfunction. Hence, strategies that maintain PDE3A function may represent an attractive approach to circumvent myocyte apoptosis and cardiac dysfunction. PMID- 17332441 TI - Keratinocyte growth factor improves repair in the injured tracheal epithelium. AB - Keratinocyte growth factor (KGF) is a critical growth factor in lung development and is a protective agent after lung injury, although the exact mechanisms of this protective effect have not yet been elucidated. Our laboratory has shown that circulating epithelial progenitor cells can traffic to the airway and that they appear to be derived from the bone marrow. On this basis, we hypothesized that KGF and its putative receptor (KGFR) would be important to these cells. We showed that the KGFR, which is found almost exclusively on epithelial cells, was present on cells in the bone marrow and circulation of mice that identified a subpopulation of cytokeratin 5+ circulating epithelial progenitor cells (CEPC). In addition, the KGFR co-localized with a population of cytokeratin 5+ basal cells in the repairing proximal airway. Systemic administration of KGF resulted in a significant increase in mobilization of cytokeratin 5+ CEPC at 6 h after injection. Administration of KGF to mouse recipients of heterotopic syngeneic tracheal transplants resulted in protection and more rapid repair of the tracheal epithelium, with an increase in the number of CEPC in the epithelium of the airway, and this effect was abrogated by blocking CEPC with anti-CXCL12 antibodies. KGF therefore appears to be an important growth factor for local resident progenitor epithelial cell repair and for mobilization and enhanced engraftment of CEPC to the injured proximal airway epithelium. PMID- 17332442 TI - Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis. AB - BACKGROUND AND PURPOSE: We updated our previous review from 1996 on the risk of rupture of unruptured intracranial aneurysms, aiming to include the newly published articles. METHODS: We reviewed all studies from our former meta analysis and performed a Medline search for new studies published after 1996. We calculated overall risks of rupture for studies with a mean follow-up time of <5, 5 to 10, and >10 years. Relative risks (RR) were calculated by comparing the risk of rupture in patients with and without potential risk factors. We aimed to perform multivariable analyses of the different risk factors with meta-regression analysis. RESULTS: We included 19 studies (10 new) with 4705 patients and 6556 unruptured aneurysms (follow-up 26 122 patient-years). The overall rupture risks were 1.2% (follow-up <5 years), 0.6% (follow-up 5 to 10 years), and 1.3% (follow up >10 years). In the univariable analysis, statistically significant risk factors for rupture were age >60 years (RR 2.0; 95% confidence interval [CI], 1.1 to 3.7), female gender (RR 1.6; 95% CI, 1.1 to 2.4), Japanese or Finnish descent (RR 3.4; 95% CI, 2.6 to 4.4), size >5 mm (RR 2.3; 95% CI, 1.0 to 5.2), posterior circulation aneurysm (RR 2.5; 95% CI, 1.6 to 4.1), and symptomatic aneurysm (RR 4.4; 95% CI, 2.8 to 6.8). Meta-regression analysis yielded implausible results. CONCLUSIONS: Age, gender, population, size, site, and type of aneurysm should be considered in the decision whether to treat an unruptured aneurysm. Pooled multivariable analyses of individual data are needed to identify independent risk factors and to provide more reliable risk estimates for individual patients. PMID- 17332443 TI - Pravastatin decreases wall shear stress and blood velocity in the internal carotid artery without affecting flow volume: results from the PROSPER MRI study. AB - BACKGROUND AND PURPOSE: Despite speculations, it is unknown whether statins affect wall shear stress (WSS). Therefore, the effect of pravastatin on WSS was investigated. METHODS: In 355 elderly individuals participating in the PROSPER study (follow up after 3 years), the effect of 40 mg pravastatin on WSS was assessed in the internal carotid artery using magnetic resonance imaging. RESULTS: WSS and blood velocity decreased both in the pravastatin group and in the placebo group but decreased faster in the pravastatin group (P<0.04, P<0.02). Blood volume flow did not differ between the groups. CONCLUSIONS: In elderly subjects, the WSS and blood velocity of the internal carotid artery declines significantly over time and this decline is more pronounced in subjects treated with 40 mg pravastatin compared with the placebo group. PMID- 17332444 TI - Mental practice in chronic stroke: results of a randomized, placebo-controlled trial. AB - BACKGROUND AND PURPOSE: Mental practice (MP) of a particular motor skill has repeatedly been shown to activate the same musculature and neural areas as physical practice of the skill. Pilot study results suggest that a rehabilitation program incorporating MP of valued motor skills in chronic stroke patients provides sufficient repetitive practice to increase affected arm use and function. This Phase 2 study compared efficacy of a rehabilitation program incorporating MP of specific arm movements to a placebo condition using randomized controlled methods and an appropriate sample size. Method- Thirty-two chronic stroke patients (mean=3.6 years) with moderate motor deficits received 30 minute therapy sessions occurring 2 days/week for 6 weeks, and emphasizing activities of daily living. Subjects randomly assigned to the experimental condition also received 30-minute MP sessions provided directly after therapy requiring daily MP of the activities of daily living; subjects assigned to the control group received the same amount of therapist interaction as the experimental group, and a sham intervention directly after therapy, consisting of relaxation. Outcomes were evaluated by a blinded rater using the Action Research Arm test and the upper extremity section of the Fugl-Meyer Assessment. RESULTS: No pre-existing group differences were found on any demographic variable or movement scale. Subjects receiving MP showed significant reductions in affected arm impairment and significant increases in daily arm function (both at the P<0.0001 level). Only patients in the group receiving MP exhibited new ability to perform valued activities. CONCLUSIONS: The results support the efficacy of programs incorporating mental practice for rehabilitating affected arm motor function in patients with chronic stroke. These changes are clinically significant. PMID- 17332445 TI - Mechanical thrombectomy of intracranial internal carotid occlusion: pooled results of the MERCI and Multi MERCI Part I trials. AB - BACKGROUND AND PURPOSE: Acute stroke from occlusion of the intracranial internal carotid artery (ICA) generally has a poor prognosis and appears to respond poorly to intravenous thrombolysis. Mechanical thrombectomy is a newly available modality for acute stroke therapy, but it is unknown whether this endovascular therapy may have a role in the specific setting of intracranial ICA occlusion. We therefore assessed the success rate of the Merci Retriever mechanical thrombectomy device in recanalization of intracranial ICA occlusions and sought to determine whether ICA recanalization with this therapy can result in better outcomes. METHODS: All patients with acute stroke from intracranial ICA occlusion were identified in the MERCI and Multi MERCI Part I trials. We determined the success rate of ICA recanalization with endovascular thrombectomy and then assessed clinical outcomes according to whether vessel recanalization was successful. RESULTS: Eighty patients with acute stroke from intracranial ICA occlusion were identified. Of these 80 patients, 53% had successful ICA recanalization with the Merci Retriever alone and 63% had ICA recanalization with use of the Merci Retriever plus adjunctive endovascular treatment. Baseline patient characteristics and procedural complications did not differ between the recanalized and nonrecanalized groups. Good clinical outcome, defined by a modified Rankin Scale of 0 to 2 at 90 days, occurred in 39% of patients with ICA recanalization (n=19 of 49) and in 3% of patients without ICA recanalization (n=1 of 30) (P<0.001; one patient was lost to follow up for 90-day modified Rankin Scale). Ninety-day mortality was 30% (n=15 of 50) in the recanalized group and 73% (n=22 of 30) in the nonrecanalized group (P<0.001). Symptomatic hemorrhage was not significantly different between the recanalized (6% [n=3 of 50]) and nonrecanalized (16.7% [n=5 of 30]) groups (P=0.14). Hemorrhage rates were also not found to be influenced by use of intravenous thrombolysis before mechanical thrombectomy. Multivariable logistic regression identified ICA recanalization (OR=28.4, 95% CI=2.6 to >99.9) and lack of history of hypertension (OR=0.15, 95% CI=0.04 to 0.57) as significant predictors of a good 90-day outcome. Failure to recanalize the ICA (OR=0.16, 95% CI=0.05 to 0.51) and age (per decade, OR=1.07, 95% CI=1.03 to 1.13) were significant predictors of mortality at 90 days. CONCLUSIONS: Mechanical thrombectomy of acute intracranial ICA occlusion using the Merci Retriever device, alone or in combination with adjunctive endovascular therapy, has a high rate of successful vessel recanalization. Subjects with successful ICA recanalization by this method have improved poststroke clinical outcome and survival compared with subjects in which the ICA is not successfully recanalized. PMID- 17332446 TI - How diagnosis-related group 559 will change the US Medicare cost reimbursement ratio for stroke centers. AB - BACKGROUND AND PURPOSE: Thrombolysis for acute ischemic stroke saves societal costs, but hospitals that practice acute stroke care appear to shoulder the burden of the cost, which exceeds reimbursement. With creation of the diagnosis related group (DRG) 559, the US Centers for Medicare and Medicaid Services pays hospitals approximately US $6000 more per case when thrombolysis is administered. We sought to determine the total cost of, and reimbursement for, acute stroke treatment with thrombolysis at a single stroke center and the economic impact of DRG 559. METHODS: Between September 2001 and December 2004, we collected data on all patients with acute stroke who received thrombolysis. We identified all hospital costs and reimbursement per patient. Financial results were expressed as a cost-reimbursement ratio: average total cost to average total reimbursement per patient. We then reanalyzed data using the projected Medicare hospital reimbursement with DRG 559. RESULTS: Sixty-seven patients with stroke (mean age, 72 years) were treated (mean length of stay, 4.4 days; mean stroke severity, National Institutes of Health Stroke Scale score of 15; and symptomatic intracranial hemorrhage rate, 7%). The cost-reimbursement ratio was 1.41 (95% CI=0.98 to 2.28) before DRG 559 and estimated to be 0.82 (95% CI=0.66 to 0.97) after DRG 559. CONCLUSIONS: Our hospital costs have traditionally exceeded Medicare reimbursement for the acute care of thrombolyzed patients with ischemic stroke, but with DRG 559, a new economically favorable cost-reimbursement ratio for hospitals will be established. PMID- 17332447 TI - Toll receptor polymorphisms and carotid artery intima-media thickness. AB - BACKGROUND AND PURPOSE: Inflammation is a key mechanism in atherosclerosis. Variation in genes encoding inflammatory responses may therefore influence atherosclerosis risk possibly through interaction with chronic infections and proinflammatory environmental risk factors such as smoking, diabetes, and obesity. The Toll-like receptor family (TLRs) genes TLR2 and TLR4, both involved in the inflammatory process, are potential candidates and TLR-4 has been previously associated with cardiovascular disease, although other studies have failed to confirm this. METHODS: A total of 3000 individuals from the prospective community-based Carotid Atherosclerosis Progression Study (CAPS) were genotyped for single nucleotide polymorphisms: TLR2 (Arg753Gln, -16934 A/T) and TLR4 (D299G, T399I). Associations were determined with common carotid artery intima media thickness (IMT) at baseline and also progression of IMT over the 3-year follow-up period. Gene-environment interactions with high sensitive C-reactive protein, smoking, body mass index, and diabetes were determined. RESULTS: There was no association between single nucleotide polymorphisms or haplotypes in either TLR4 or TLR2 and either baseline IMT or progression of IMT over the 3-year follow up. There were no interactions among the three proinflammatory risk factors. No genotype or haplotype was associated with high sensitive C-reactive protein. CONCLUSIONS: In this large community population, we found no evidence for genetic variation in these two TLRs being risk factors for increased IMT either directly or through interaction with proinflammatory risk factors. We were unable to confirm associations with the TLR4 polymorphisms reported in previous smaller studies. PMID- 17332448 TI - Incidence and risk factors for stroke in type 2 diabetic patients: the DAI study. AB - BACKGROUND AND PURPOSE: Type 2 diabetes mellitus is a strong predictor of cerebrovascular disease, yet few studies have assessed the incidence of stroke and the role of other risk factors in unselected type 2 diabetes mellitus populations. METHODS: We prospectively followed-up 14,432 type 2 diabetes mellitus patients, aged 40 to 97 years, with and without a history of cardiovascular disease at enrollment, and we estimated the incidence of stroke and the hazards ratios with respect to clinical variables. RESULTS: During a 4 year follow-up, 296 incident stroke events were recorded. In persons with no history of cardiovascular disease, the age-standardized incidence of stroke (per 1000 person-years) was 5.5 (95% confidence interval, 4.2 to 6.8) in men and 6.3 (95% confidence interval, 4.5 to 8.2) in women. In persons with a history of cardiovascular disease, it was 13.7 (95% confidence interval, 7.5 to 19.8) in men and 10.8 (95% confidence interval, 7.3 to 14.4) in women. The hazards ratios of stroke incidence varied according to age, sex, and history of cardiovascular disease. Among men with no history, HbA1c and smoking were predictors of stroke. Among patients with a history, the risk factors were, in men, therapy with insulin plus oral agents, treated high total cholesterol and low HDL cholesterol, whereas in women microvascular complications were a risk factor. Previous stroke was a strong predictor of stroke in both sexes. CONCLUSIONS: Age and previous stroke are the main predictors of stroke in diabetes. The combined role of Hba1c, microvascular complications, low HDL cholesterol, and treatment with insulin plus oral agents highlights the importance of diabetic history and clinical background in the development of stroke. PMID- 17332449 TI - IL1RN VNTR polymorphism in ischemic stroke: analysis in 3 populations. AB - BACKGROUND AND PURPOSE: Genetic factors influence risk for ischemic stroke and likely do so at multiple steps in the pathogenic process. Variants in genes related to inflammation contribute to risk of stroke. The purpose of this study was to confirm our earlier finding of an association between allele 2 of a variable number tandem repeat of the IL-1 receptor antagonist gene (IL1RN) and cerebrovascular disease. METHODS: An association study of the variable number tandem repeat genotype with ischemic stroke and stroke subtypes was performed on samples from a North American study of affected sibling pairs concordant for ischemic stroke and 2 North American cohorts of prospectively ascertained ischemic stroke cases and unrelated controls. DNA analysis was performed on cases and controls, stratified by race. RESULTS: After adjustment for age, sex, and stroke risk factors, the odds ratio for association of allele 2 and ischemic stroke was 2.80 (95% confidence interval, 1.29 to 6.11; P=0.03) for the white participants. The effect of allele 2 of IL1RN on stroke risk most closely fits a recessive genetic model (P=0.009). For the smaller sample of nonwhite participants, the results were not significant. CONCLUSIONS: Allele 2 of IL1RN, present in nearly one-quarter of stroke patients, may contribute to genetic risk for ischemic stroke and confirm the previously identified association with cerebrovascular disease. These results are driven by the association in the white participants. Further exploration in a larger nonwhite sample is warranted. PMID- 17332450 TI - Autonomic ganglionic blockade does not prevent reduction in cerebral blood flow velocity during orthostasis in humans. AB - BACKGROUND AND PURPOSE: The underlying mechanisms for reductions in cerebral blood flow (CBF) during orthostasis are not completely understood. This study tested the hypothesis that sympathetic activation causes cerebral vasoconstriction leading to reductions in CBF during lower body negative pressure (LBNP). METHODS: CBF velocity, arterial pressure, and end-tidal CO(2) were measured during LBNP (-30 to -50 mm Hg) in 11 healthy subjects before and after autonomic ganglionic blockade with trimethaphan. Arterial partial pressure of CO(2) also was measured in a subgroup of 5 subjects. Mean arterial pressure during LBNP after blockade was maintained by infusion of phenylephrine. RESULTS: Before blockade, mean arterial pressure did not change during LBNP. However, CBF velocity was reduced in all subjects by 14% (P<0.05). Systolic and pulsatile (systolic-diastolic) CBF velocity were reduced by 18% and 28%, respectively, associated with significant reductions in pulse arterial pressure and end-tidal CO(2) (all P<0.05). After blockade, mean arterial pressure during LBNP was well maintained and even increased slightly with infusion of phenylephrine. However, reductions in mean, systolic, and pulsatile CBF velocity, pulse arterial pressure, and ETCO(2) were similar to those before blockade. In contrast to reductions in end-tidal CO(2), arterial partial pressure of CO(2) did not change during LBNP. CONCLUSIONS: These data, contrary to our hypothesis, demonstrate that sympathetic vasoconstriction is not the primary mechanism underlying reductions in CBF during moderate LBNP. We speculate that diminished pulse arterial pressure or pulsatile blood flow may reduce cerebral vessel wall shear stress and contribute to reductions in CBF during orthostasis through flow mediated regulatory mechanisms. PMID- 17332451 TI - Life expectancy after perimesencephalic subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: Patients with a perimesencephalic nonaneurysmal subarachnoid hemorrhage are not at risk for rebleeding in the initial years after the hemorrhage. Nevertheless, uncertainty remains on the long-term prognosis after perimesencephalic hemorrhage, and former patients are often considered high risk cases for health insurance or are denied life insurance. We performed a very long-term follow-up study of a large consecutive series of such patients and compared mortality in this cohort with that in the general population. METHODS: All patients with a perimesencephalic hemorrhage (defined by pattern of hemorrhage on computed tomography within 72 hours after onset and absence of aneurysm) admitted between 1983 and 2005 to our service were followed-up by telephone. For patients who had died, we retrieved age and cause of death. We compared the age- and sex-specific mortality of this cohort with that of the general population by means of standardized mortality ratios with corresponding 95% confidence intervals. RESULTS: The cohort consisted of 160 patients, with a total number of patient-years of 1213. No new episodes of subarachnoid hemorrhage had occurred. During follow-up 11 patients had died; the expected number of deaths based on mortality rates in the general population (adjusted for age and gender) was 18.1. The standardized mortality ratio was 0.61 (95% confidence interval, 0.34 to 1.1). CONCLUSIONS: Patients with perimesencephalic hemorrhage have a normal life expectancy and are not at risk for rebleeding. No restrictions should be imposed on these patients by physicians or health or life insurance companies. PMID- 17332452 TI - Autopsy prevalence of coronary atherosclerosis in patients with fatal stroke. AB - BACKGROUND AND PURPOSE: Myocardial infarction (MI) is the leading cause of long term mortality in patients with stroke, yet the prevalence of coronary atherosclerosis in these individuals is unknown. The objective of the study was to establish the prevalence of coronary atherosclerosis and MI after fatal stroke. METHODS: Using an autopsy data bank, we studied the prevalence of coronary plaques and coronary stenoses >50% and pathologic evidence of MI in 803 consecutive autopsies of neurologic patients. RESULTS: Coronary plaques, coronary stenoses, and MI were present in 72.4%, 37.5%, and 40.8%, respectively, of the 341 patients with stroke and in 26.8%, 10.1%, and 12.8%, respectively, of the 462 patients with other neurologic diseases (P<0.001). Two-thirds of cases of MI were clinically silent and found at autopsy. Compared with other neurologic diseases, and after adjusting for age, gender, and heart weight, the odds ratios (95% confidence intervals) of the presence of coronary plaques, coronary stenosis, and MI in stroke patients were 3.81 (2.66 to 5.46), 2.80 (1.85 to 4.25), and 2.34 (1.58 to 3.46), respectively. The frequency of coronary atherosclerosis and MI was similar between stroke subtypes. The prevalence of coronary plaques, coronary stenosis, and MI was 79.0%, 42.9%, and 46.0%, respectively, in the presence of plaques in any segment of the extracranial and intracranial brain arteries, and 50.8%, 17.9%, and 23.9%, respectively, in the absence of plaques (adjusted P<0.01). Coronary atherosclerosis was also related to the severity of atherosclerosis in any segment of the cerebral arteries (adjusted probability value for linear trend <.005). CONCLUSIONS: Coronary atherosclerosis and MI are highly prevalent in patients who died from a stroke regardless of the etiology. They are more frequent when atherosclerosis is present in the carotid and cerebral arteries. They are also common in stroke patients with no evidence of carotid or cerebral atherosclerosis. PMID- 17332453 TI - High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet activation in 880 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors, stroke risk stratification schema, and prognosis. AB - BACKGROUND AND PURPOSE: There is now considerable evidence that atrial fibrillation is associated with an inflammatory state. We tested the hypothesis that plasma levels of C-reactive protein (CRP; an index of inflammation) and soluble CD40 ligand (an index of platelet activation, with links to inflammation) could be related to 3 established stroke risk stratification schema (SPAF, CHADS(2), and NICE), recognized stroke risk factors or other cardiovascular disease, and prognosis. METHODS: We studied 880 subjects with atrial fibrillation recruited from subjects receiving aspirin 325 mg/d (alone or combined with fixed inefficacious doses of warfarin) from the Stroke Prevention in Atrial Fibrillation (SPAF) III clinical trial. CRP and soluble CD40 ligand were measured by enzyme-linked immunosorbent assay. RESULTS: With respect to the SPAF III stroke risk stratification criteria, those with moderate to high risk had the highest levels of CRP (Kruskal Wallis test, P<0.001), but those with the highest risk had the lowest levels of soluble CD40 ligand (P=0.01). Similarly, CRP levels increased in a positive fashion with increasing stroke risk with respect to the CHADS(2) and NICE risk stratification criteria, whereas soluble CD40 ligand levels were negatively associated with stroke risk. CRP levels were higher among those patients with raised body mass index, diabetes, hypertension, ischemic heart disease, peripheral vascular disease, and recent heart failure, but not those with thromboembolism. Patients were followed-up for a mean time of 453 (standard deviation, 229) days, and all-cause mortality (log rank test, P=0.001), and vascular events (P=0.05), but not stroke, were more common in patients with high CRP levels. Soluble CD40 ligand levels were not related to stroke, vascular events, or all-cause mortality. CONCLUSIONS: Among atrial fibrillation patients, CRP was positively correlated to stroke risk and related to stroke risk factors and prognosis (mortality, vascular events). Soluble CD40 ligand levels were lowest in those at moderate to high risk of stroke and not related to prognosis. The use of CRP in risk stratification for atrial fibrillation merits further study. PMID- 17332454 TI - Punding as a complication of brain stem stroke?: report of a case. AB - BACKGROUND AND PURPOSE: Stereotyped motor behaviors, known as "punding," originally described among amphetamine abusers have only recently been reported in Parkinson disease associated with both pro-(eg, levodopa) or anti-(eg, quetiapine) dopaminergic therapy. We describe a non-Parkinson disease case of nonpharmacologically induced punding as a complication of a brain stem cardiovascular accident. SUMMARY OF CASE: A 54-year-old man, after an episode of brain stem cardiovascular accident secondary to basilar artery thrombosis, was noted to endlessly purchase and hoard food items and to write, copy and organize recipes. His activity was excessive, disruptive and affected his interaction with family members. The patient's punding behaviors significantly improved with an increased dose of sertraline from 100 mg to 150 mg per day. CONCLUSIONS: Our patient's presentation was most consistent with punding, but interestingly was not a result of dopaminergic therapy. Moreover, improvement of his behavior was noted with a selective serotonin reuptake inhibitor, further questioning the dopaminergic hypothesis of punding. PMID- 17332455 TI - The case for modality-specific outcome measures in clinical trials of stroke recovery-promoting agents. AB - Clinical trials for acute stroke treatments have often used composite clinical rating scales as primary outcome measures of treatment efficacy. Recent preclinical and clinical studies highlight the opportunity to administer treatments in the subacute and chronic phase of stroke to promote neurological recovery. Because different neurological deficits recover to different extents at different rates after stroke, putative stroke recovery-promoting treatments may exert differential effects on various functional aspects of stroke recovery. For this reason, we propose that the use of modality-specific outcome measures may be best suited as primary end points in clinical trials of stroke recovery-promoting agents. The use of such end points may result in a more selective labeling of stroke recovery treatments. PMID- 17332456 TI - Attitudes and current practice of primary care physicians in acute stroke management. AB - BACKGROUND AND PURPOSE: Stroke patients often report that primary care physicians (PCPs) are their first medical contact after onset of symptoms. We studied PCP attitudes and current practice in early management of suspected stroke patients. METHODS: A cross-sectional survey was conducted among 714 general practitioners, internists, and neurologists providing acute primary care for stroke patients in 4 different regions in Germany. PCP attitudes and practices were assessed with standardized questionnaires and case vignettes presenting suspected stroke patients contacting PCPs either by phone or in practice. Factors influencing the decision of the PCPs to admit patients with clear stroke symptoms as medical emergency to hospital were assessed using multivariate analysis. RESULTS: In total, 395 PCPs participated in the study (55.3%). Most PCPs agreed that stroke (94.7%) and transient ischemic attack (84.8%) were medical emergencies. In case vignettes, admission to hospital as medical emergency was preferred management after first contact to patients with clear stroke symptoms by phone or in practice (68.9% and 65.6%, respectively). Outpatient clarification was the preferred option of PCPs in patients with unclear stroke symptoms contacting PCPs by phone or in practice (54.7% and 75.5%, respectively) and in transient ischemic attack patients (50.9%). Working as general practitioner (odds ratio, 0.3; 95% confidence interval, 0.2 to 0.6) and practice location outside metropolitan area (P=0.002) independently decreased probability of admitting suspected stroke patients as medical emergency when first contact to PCPs was by phone. PCP agreement that all stroke and transient ischemic attack patients must be admitted to hospital increased probability for early hospitalization of stroke and transient ischemic attack patients when first contact was in practice (odds ratio, 2.0; 95% confidence interval, 1.2 to 3.3, and odds ratio, 1.8; 95% confidence interval, 1.1 to 2.8, respectively). CONCLUSIONS: Stroke and transient ischemic attack were well recognized as medical emergencies by PCPs in our study. However, only two-thirds of PCP would immediately admit stroke suspected patients with clear symptoms to hospital as medical emergency. PMID- 17332457 TI - Novel protein transduction method by using 11R: an effective new drug delivery system for the treatment of cerebrovascular diseases. AB - BACKGROUND AND PURPOSE: A motif of 11 consecutive arginines (11R) is reported to be one of the most effective protein transduction domains for introducing proteins into the cell membrane. We therefore examined the transduction efficiency of 11R in cerebral arteries. METHODS: Basilar arteries (BAs) obtained from rats were incubated with either 11R-enhanced green fluorescent protein (11R EGFP) or EGFP without 11R. After incubation, expression of 11R-EGFP or EGFP in BA serial sections was observed by fluorescence microscope. In an additional in vivo experiment, 11R-EGFP or EGFP was injected into the cisterna magna with or without subarachnoid hemorrhage. The 11R-EGFP or EGFP was injected just after the autologous blood injection, and then the expression of 11R-EGFP or EGFP in BA sections was also observed by fluorescence microscope. RESULTS: The 11R-EGFP signal was much stronger than that of EGFP in all layers of the rat BA, in both in vivo and ex vivo experiments. Moreover, the 11R-EGFP was transduced into the BA immediately (2 hours after the injection). Interestingly, 11R-fused fluorescent protein was transduced especially into the tunica media of the BA. CONCLUSIONS: The 11R-fused fluorescent protein effectively penetrates into all layers of the rat BA, especially into the tunica media. This is the first study to our knowledge to demonstrate the successful transduction of a protein transduction domain fused protein into the cerebral arteries. PMID- 17332458 TI - Middle cerebral artery stenosis: stenting is one of the options: no. PMID- 17332459 TI - Middle cerebral artery stenosis: stenting is one of the options: yes. PMID- 17332460 TI - Stenting for middle cerebral artery stenosis: inevitable but when and how. PMID- 17332462 TI - New MRI brain lesions as surrogate outcome for carotid stenting with and without cerebral protection. PMID- 17332463 TI - Multifactorial bases of stroke after cardiac surgery. PMID- 17332465 TI - Validation of transcranial Doppler with computed tomography angiography in acute cerebral ischemia. AB - BACKGROUND AND PURPOSE: Both transcranial Doppler (TCD) and spiral computed tomography angiography (CTA) are used for noninvasive vascular assessment tools in acute stroke. We aimed to evaluate the diagnostic accuracy of TCD against CTA in patients with acute cerebral ischemia. METHODS: Consecutive patients presenting to the Emergency Department with symptoms of acute (<24 hours) cerebral ischemia underwent emergent high-resolution brain CTA with a multidetector helical scanner. TCD was performed at bedside with a standardized, fast-track insonation protocol before or shortly (<2 hours) after completion of the CTA. Previously published diagnostic criteria were prospectively applied for TCD interpretation independent of angiographic findings. RESULTS: A total of 132 patients (74 men, mean+/-SD age 63+/-15 years) underwent emergent neurovascular assessment with brain CTA and TCD. Compared with CTA, TCD showed 34 true positive, 9 false-negative, 5 false-positive, and 84 true-negative studies (sensitivity 79.1%, specificity 94.3%, positive predictive value 87.2%, negative predictive value 90.3%, and accuracy 89.4%). In 9 cases (7%), TCD showed findings complementary to the CTA (real-time embolization, collateralization of flow with extracranial internal carotid artery disease, alternating flow signals indicative of steal phenomenon). CONCLUSIONS: Bedside TCD examination yields satisfactory agreement with urgent brain CTA in the evaluation of patients with acute cerebral ischemia. TCD can provide real-time flow findings that are complementary to information provided by CTA. PMID- 17332466 TI - Recanalization and outcome after intra-arterial thrombolysis in middle cerebral artery and internal carotid artery occlusion: does sex matter? AB - BACKGROUND AND PURPOSE: Recent studies have reported sex differences in recanalization and outcome after intravenous thrombolysis (IVT) in acute ischemic stroke. METHODS: We analyzed sex differences in outcome in consecutive patients with middle cerebral artery (MCA) M1 or M2 and internal carotid artery (ICA) occlusion treated with intra-arterial thrombolysis (IAT). Recanalization immediately after thrombolysis and outcome after 3 months were assessed. RESULTS: Two hundred five patients (111 men) with MCA and 43 (22 men) with ICA occlusion were identified. Baseline variables did not differ between the sexes except for a higher prevalence of smokers among men in the MCA group (31% vs 12%; P=0.001). Partial or complete recanalization (TIMI flow 2 or 3) of the MCA was observed in 71 (75%) women and 80 (72%) men (P=0.488). In the ICA group, 14 (67%) women and 11 men (50%) showed TIMI 2 or 3 recanalization (P=0.425). Favorable outcome (modified Rankin Scale score 0 to 2) was seen in 57 women (61%) and 63 men (57%) with MCA occlusion (P=0.512) and in 6 women (28%) and 4 men (18%) with ICA occlusion (P=0.656). After multiple-regression analyses, there was still no association between sex and outcome (P=0.763 for MCA and P=0.813 for ICA occlusion) or recanalization (P=0.488 for MCA and P=0.104 for ICA occlusion). CONCLUSIONS: There was no association between sex and recanalization or outcome after IAT. These findings are in contrast to previous studies reporting better recanalization and outcome after IVT in women and might have implications in the selection of patients for IAT or IVT. PMID- 17332467 TI - Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice. AB - BACKGROUND AND PURPOSE: The chemokine, monocyte chemoattractant protein-1 (CCL2), is a major factor driving leukocyte infiltration into the brain parenchyma in a variety of neuropathologic conditions associated with inflammation, including stroke. In addition, recent studies indicate that CCL2 and its receptor (CCR2) could have an important role in regulating blood-brain barrier (BBB) permeability. This study evaluated the role of the CCL2/CCR2 axis in regulating postischemic inflammation, BBB breakdown, and vasogenic edema formation. METHODS: CCR2(-/-) and CCR2(+/+) mice were subjected to focal transient cerebral ischemia. BBB permeability and brain edema formation were observed at days 1 and 5 of reperfusion by evaluating the product surface area for fluorescein isothiocyanate albumin and measuring water and electrolyte contents. Immunohistochemistry was used to assess leukocyte infiltration. cDNA gene and protein arrays for inflammatory cytokines were used to assess inflammatory profiles in CCR2(+/+) and CCR2(-/-) mice. RESULTS: CCR2(-/-) mice had reduced infarct sizes and significantly reduced BBB permeability and brain edema formation in the affected ischemic hemisphere compared with CCR2(+/+) mice. This reduction in injury was closely associated with reduced infiltration of not only monocytes but also neutrophils (7- and 4-fold decreases, respectively). In addition, CCR2(-/-) mice had reduced expression/production of inflammatory cytokines during reperfusion. CONCLUSIONS: These data suggest that inhibiting the CCL2/CCR2 axis affects brain reperfusion outcome by reducing brain edema, leukocyte infiltration, and inflammatory mediator expression. PMID- 17332468 TI - Granulocyte-macrophage colony-stimulating factor-induced vessel growth restores cerebral blood supply after bilateral carotid artery occlusion. AB - BACKGROUND AND PURPOSE: Hemodynamic compromise due to occlusive cerebrovascular disease is associated with an increased stroke risk. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been suggested to stimulate collateral blood vessel growth in various models of hemodynamic compromise. The purpose of this study was to investigate the effects of GM-CSF on cerebral hemodynamics and vessel growth in a rat model of chronically impaired cerebral blood flow (CBF). METHODS: Male Sprague-Dawley rats underwent sequential bilateral carotid artery occlusion (BCO) and were treated with GM-CSF or saline for 6 weeks. Sham-occluded animals served as a control group. Baseline CBF was measured by iodo[(14)C]antipyrine autoradiography, and cerebrovascular reserve capacity was assessed by laser-Doppler flowmetry after application of 20 mg/kg body weight acetazolamide. The capillary density and arterioles immunopositive for alpha smooth muscle actin were counted on brain sections. The cerebral angioarchitecture was visualized with a latex perfusion technique. RESULTS: Baseline CBF as measured by iodo[(14)C]antipyrine autoradiography was not affected by BCO. The cerebrovascular reserve capacity, however, was significantly impaired 1 week after BCO. CBF and cerebrovascular reserve capacity recovered completely in GM-CSF-treated animals but not in solvent-treated animals. Histologic analysis of the hippocampus revealed integrity of the hypoxia vulnerable neurons in all animals. The capillary density showed a very mild increase in GM-CSF-treated animals. However, the number of intraparenchymal and leptomeningeal arterioles was significantly higher in GM-CSF-treated animals than in both other groups. CONCLUSIONS: Long-term GM-CSF treatment in a BCO model in rats leads to restoration of impaired cerebral hemodynamics and accompanies structural changes in the resistance-vessel network. PMID- 17332469 TI - T cell-associated CD18 but not CD62L, ICAM-1, or PSGL-1 is required for the induction of chronic colitis. AB - The induction and perpetuation of chronic colitis are thought to involve a complex set of adhesive interactions between T cells and endothelial cells located on the vasculature within secondary lymphoid tissue and the intestine. The objective of this study was to assess the roles of T cell-associated CD18, CD62L (L-selectin), ICAM-1, and P-selectin glycoprotein ligand-1 (PSGL-1) in the induction of chronic colitis in mice. CD4(+)CD25(-) T cells derived from either wild-type (WT), CD18-deficient [CD18 knockout (KO)], CD62L KO, ICAM-1 KO, or PSGL 1 KO mice were adoptively transferred into recombinase activating gene-1 (RAG-1) deficient mice (RAG KO mice) to assess the potential of these T cells to induce chronic colitis. At 8-10 wk following T cell transfer, we observed moderate to severe colitis as assessed by increases in colon weight-to-length ratios and by blinded histopathological analysis. In contrast, we found that transfer of CD18 KO T cells into RAG KO recipients resulted in the significant attenuation of colonic inflammation in these mice. Furthermore, we observed fewer infiltrating CD4(+) T cells in the colonic lamina propria in the CD18 KO-->RAG KO group compared with the WT-->RAG KO group. Finally, message levels of colonic TNF alpha, IL-1beta, and IFN-gamma were significantly reduced in CD18 KO-->RAG KO mice compared with colitic control animals. We conclude that T cell-associated CD18, but not CD62L, ICAM-1, or PSGL-1, is required for the development of chronic colitis. PMID- 17332470 TI - Functional evidence for Na+-activated K+ channels in circular smooth muscle of the opossum lower esophageal sphincter. AB - Na(+) reduction induces contraction of opossum lower esophageal sphincter (LES) circular smooth muscle strips in vitro; however, the mechanism(s) by which this occurs is unknown. The purpose of the present study was to investigate the electrophysiological effects of low Na(+) on opossum LES circular smooth muscle. In the presence of atropine, quanethidine, nifedipine, and substance P, conventional intracellular electrodes recorded a resting membrane potential (RMP) of -37.5 +/- 0.9 mV (n = 4). Decreasing [Na(+)] from 144.1 to 26.1 mM by substitution of equimolar NaCl with choline Cl depolarized the RMP by 7.1 +/- 1.1 mV. Whole cell patch-clamp recordings revealed outward K(+) currents that began to activate at -60 mV using 400-ms stepped test pulses (-120 to +100 mV) with increments of 20 mV from holding potential of -80 mV. Reduction of [Na(+)] in the bath solution inhibited K(+) currents in a concentration-dependent manner. Single channels with conductance of 49-60 pS were recorded using cell-attached patch clamp configurations. The channel open probability was significantly decreased by substitution of bath Na(+) with equimolar choline. A 10-fold increase of [K(+)] in the pipette shifted the reversal potential of the single channels to the positive by -50 mV. These data suggest that Na(+)-activated K(+) channels exist in the circular smooth muscle of the opossum LES. PMID- 17332471 TI - Cause-effect relationships between zymogen activation and other early events in secretagogue-induced acute pancreatitis. AB - We have hypothesized that the colocalization of digestive zymogens with lysosomal hydrolases, which occurs during the early stages of every experimental pancreatitis model, facilitates activation of those zymogens by lysosomal hydrolases such as cathepsin B and that this activation triggers acute pancreatitis by leading to acinar cell injury. Some, however, have argued that the colocalization phenomenon may be the result, rather than the cause, of zymogen activation during pancreatitis. To resolve this controversy and explore the causal relationships between zymogen activation and other early pancreatitis events, we induced pancreatitis in mice by repeated supramaximal secretagogue stimulation with caerulein. Some animals were pretreated with the cathepsin B inhibitor CA-074 me to inhibit cathepsin B, prevent intrapancreatic activation of digestive zymogens, and reduce the severity of pancreatitis. We show that inhibition of cathepsin B by pretreatment with CA-074 me prevents intrapancreatic zymogen activation and reduces organellar fragility, but it does not alter the caerulein-induced colocalization phenomenon or subcellular F-actin redistribution or prevent caerulein-induced activation of NF-kappaB, ERK1/2, and JNK or upregulated expression of cytochemokines. We conclude 1) that the colocalization phenomenon, F-actin redistribution, activation of proinflammatory transcription factors, and upregulated expression of cytochemokines are not the results of zymogen activation, and 2) that these early events in pancreatitis are not dependent on cathepsin B activity. In contrast, zymogen activation and increased subcellular organellar fragility during caerulein-induced pancreatitis are dependent on cathepsin B activity. PMID- 17332472 TI - Caerulein-induced intracellular pancreatic zymogen activation is dependent on calcineurin. AB - Aberrant cytosolic Ca(2+) flux in pancreatic acinar cells is critical to the pathological pancreatic zymogen activation observed in acute pancreatitis, but the downstream effectors are not known. In this study, we examined the role of Ca(2+)-activated protein phosphatase 2B (or calcineurin) in zymogen activation. Isolated pancreatic acinar cells were stimulated with supraphysiological caerulein (100 nM) with or without the calcineurin inhibitors FK506 or cell permeable calcineurin inhibitory peptide (CiP). Chymotrypsin activity was measured as a marker of zymogen activation, and the percent amylase secretion was used as a measure of enzyme secretion. Cytosolic Ca(2+) changes were recorded in acinar cells loaded with the intermediate Ca(2+)-affinity dye fluo-5F using a scanning confocal microscope. A 50% reduction in chymotrypsin activity was observed after pretreatment with 1 microM FK506 or 10 microM CiP. These pretreatments did not affect amylase secretion or the rise in cytosolic Ca(2+) after caerulein stimulation. These findings suggest that calcineurin mediates caerulein-induced intra-acinar zymogen activation but not enzyme secretion or the initial caerulein-induced cytosolic Ca(2+) signal. PMID- 17332473 TI - Protein-protein interactions and membrane localization of the human organic solute transporter. AB - Two proteins that mediate bile acid export from the ileal enterocyte, organic solute transporter (OST)-alpha and -beta, have recently been identified. It is unclear whether these two proteins associate directly and how they interact to mediate transport function and membrane localization. In this study, the protein protein interactions, transport functions, and membrane localization of human (h)OST-alpha and -beta proteins were examined. The results demonstrated that coexpression of hOST-alpha and -beta in transfected cells resulted in a three- to fivefold increase of the initial rate of taurocholate influx or efflux compared with cells expressing each protein individually and nontransfected cells. Confocal microscopy demonstrated plasma membrane colocalization of hOST-alpha and -beta proteins in cells cotransfected with hOST-alpha and -beta cDNAs. Protein protein interactions between hOST-alpha and -beta were demonstrated by mammalian two-hybrid and coimmunoprecipitation analyses. Truncation of the amino-terminal 50 amino acid extracellular residues of hOST-alpha abolished its interaction with hOST-beta and led to an intracellular accumulation of the two proteins and to only background levels of taurocholate transport. In contrast, carboxyl-terminal 28 amino acid truncated hOST-alpha still interacted with hOST-beta, and majority of this cytoplasmic tail-truncated protein was expressed on the basolateral membrane when it was stably cotransfected with hOST-beta protein in Madin-Darby canine kidney cells. In summary, hOST-alpha and -beta proteins are physically associated. The intracellular carboxyl-terminal domain of hOST-alpha is not essential for this interaction with hOST-beta. The extracellular amino-terminal fragment of hOST-alpha may contain important information for the assembly of the heterodimer and trafficking to the plasma membrane. PMID- 17332474 TI - Enhancement of intragastric acid stability of a fat emulsion meal delays gastric emptying and increases cholecystokinin release and gallbladder contraction. AB - Preprocessed fatty foods often contain calories added as a fat emulsion stabilized by emulsifiers. Emulsion stability in the acidic gastric environment can readily be manipulated by altering emulsifier chemistry. We tested the hypothesis that it would be possible to control gastric emptying, CCK release, and satiety by varying intragastric fat emulsion stability. Nine healthy volunteers received a test meal on two occasions, comprising a 500-ml 15% oil emulsion with 2.5% of one of two emulsifiers that produced emulsions that were either stable (meal A) or unstable (meal B) in the acid gastric environment. Gastric emptying and gallbladder volume changes were assessed by MRI. CCK plasma levels were measured and satiety scores were recorded. Meal B layered rapidly owing to fat emulsion breakdown. The gastric half-emptying time of the aqueous phase was faster for meal B (72 +/- 13 min) than for meal A (171 +/- 35 min, P < 0.008). Meal A released more CCK than meal B (integrated areas, respectively 1,095 +/- 244 and 531 +/- 111 pmol.min.l(-1), P < 0.02), induced a greater gallbladder contraction (P < 0.02), and decreased postprandial appetite (P < 0.05), although no significant differences were observed in fullness and hunger. We conclude that acid-stable emulsions delayed gastric emptying and increased postprandial CCK levels and gallbladder contraction, whereas acid-instability led to rapid layering of fat in the gastric lumen with accelerated gastric emptying, lower CCK levels, and reduced gallbladder contraction. Manipulation of the acid stability of fat emulsion added to preprocessed foods could maximize satiety signaling and, in turn, help to reduce overconsumption of calories. PMID- 17332475 TI - beta-Catenin is critical for early postnatal liver growth. AB - The Wnt/beta-catenin pathway plays an important role in embryonic liver development, morphogenesis, and organogenesis. Here, we report on the activation of beta-catenin during early postnatal liver growth. Modulation of beta-catenin expression was studied in CD-1 mice livers over a time course of 0 to 30 postnatal days (PD) and 3 mo. Increases in total and active beta-catenin were observed in developing livers from PD 5 to 20. A concomitant increase in the beta catenin-transcription factor (TCF) complex along with nuclear and cytoplasmic beta-catenin was also evident, which coincided with ongoing hepatocyte proliferation by PCNA immunohistochemistry. This activation of beta-catenin was multifactorial, including cyclical inhibition of glycogen synthase kinase-3beta, suppression of casein kinase-IIalpha, and a transient increase in beta-catenin gene expression. Coprecipitation experiments revealed the formation of the beta catenin-cadherin complex at PD 5, whereas adequate beta-catenin-c-Met complex at the hepatocyte membrane did not form until PD 20, which might be contributing to the free beta-catenin pool during early postnatal growth. Furthermore, beta catenin liver-specific knockout mice exhibited smaller livers at PD 30, secondary to diminished hepatocyte proliferation. These data indicate that the activation of beta-catenin is critical for early postnatal liver growth and development. PMID- 17332476 TI - Gastrin regulates the TFF2 promoter through gastrin-responsive cis-acting elements and multiple signaling pathways. AB - Trefoil family factor 2 (TFF2) is expressed in gastrointestinal epithelial cells where it serves to maintain mucosal integrity and promote epithelial repair. The peptide hormone, gastrin, stimulates acid secretion but also induces proliferation of the acid-secreting mucosa. Because the relationship between these peptides of overlapping function is not understood, we chose to investigate the regulatory effect of gastrin on TFF2 expression. The expression of mRNA and protein of TFF2 was determined by RT-PCR and immunohistochemical staining, respectively. A series of truncated and mutant murine TFF2 promoter constructs was generated. Promoter activity was assessed using dual luciferase reporter assays. Gastrin-responsive DNA-binding sites in the TFF2 promoter were evaluated by electrophoretic mobility shift assay. Gastrin significantly increased the level of endogenous mRNA of TFF2 in the gastrin receptor-expressing AGS-E gastric cancer cell line in a time- and dose-dependent manner. TFF2 protein expression in the gastric fundus was elevated in hypergastrinemic (INS-GAS) transgenic mice and reduced in gastrin-deficient mice. Gastrin treatment increased TFF2 promoter activity through cis-acting regions, containing CCAATA- and GC-rich enhancers. Pretreatment with Y-F476, a gastrin/CCK(B) receptor antagonist, abolished gastrin dependent promoter activity. Inhibitors of protein kinase C (PKC), mitogen/extracellular signal-regulated kinase (MEK1), and phosphatidylinositol 3 kinase (PI 3-kinase) reduced gastrin-dependent TFF2 promoter activity, whereas an epithelial growth factor receptor (EGFR) inhibitor had no effect. We found that gastrin regulates TFF2 transcription through a GC-rich DNA-binding site and a PKC , MEK1- and PI 3-kinase-dependent but EGFR-independent pathway. Regulation of TFF2 by gastrin may play a role in the maintenance and repair of the gastrointestinal mucosa. PMID- 17332477 TI - Disruption of the murine intestinal alkaline phosphatase gene Akp3 impairs lipid transcytosis and induces visceral fat accumulation and hepatic steatosis. AB - Intestinal alkaline phosphatase (IAP) is involved in the process of fat absorption, a conclusion confirmed by an altered lipid transport and a faster body weight gain from 10 to 30 wk in both male and female mice with a homozygous null mutation of the IAP coding gene (Akp3(-/-) mice). This study was aimed to delineate morphologically and quantitatively the accelerated lipid absorption in male Akp3(-/-) mice. Feeding a corn oil bolus produced an earlier peak of triacylglycerol in serum (2 vs. 4 h for Akp3(-/-) and wild-type mice, respectively) and an approximately twofold increase in serum triacylglycerol concentration in Akp3(-/-) mice injected with a lipolysis inhibitor, Triton WR 1339. A corn oil load induced the threefold enlargement of the Golgi vacuoles in male wild-type mice but not in Akp3(-/-) mice, indicating that absorbed lipids rarely reached the Golgi complex and that the transcytosis of lipid droplets does not follow the normal pathway in male Akp3(-/-) mice. Force feeding an exaggerated fat intake by a 30% fat chow for 10 wk induced obesity in both male Akp3(-/-) and wild-type mice, and therefore no phenotypic difference was observed between the two. On the other hand, the forced high-fat chow induced an 18% greater body weight gain, hepatic steatosis, and visceral fat accumulation in female Akp3(-/-) mice but not in female wild-type controls. These results provide further evidence that IAP is involved in the regulation of the lipid absorption process and that its absence leads to progressive metabolic abnormalities in certain fat-forced conditions. PMID- 17332478 TI - Decreased MAPK- and PGE2-dependent IL-11 production in Gialpha2-/- colonic myofibroblasts. AB - Mice deficient in the G-protein alpha subunit G(i)alpha(2) spontaneously develop colitis and colon cancer. IL-11 is a pleiotropic cytokine known to protect the intestinal epithelium from injury in animal models of colitis and is produced by subepithelial myofibroblasts in response to inflammatory mediators including TGF beta, IL-1beta, and PGE(2). Arachidonic acid release and subsequent PGE(2) production is significantly decreased in the colonic mucosa of G(i)alpha(2)-/- mice, and we hypothesized that this would affect mucosal IL-11 production. Mucosal levels of IL-11 were found to be significantly decreased in G(i)alpha(2) /- mice despite the presence of mild colitis. Primary cultures of G(i)alpha(2)-/- intestinal and colonic myofibroblasts (IMF and CMF, respectively) produced less basal and TGF-beta or IL-1beta-stimulated IL-11 mRNA and protein than wild-type cells. Inhibitors of ERK or p38 MAPK activation dose dependently inhibited IMF and CMF IL-11 production in response to TGF-beta stimulation, whereas 16,16 dimethyl-PGE(2) and prostanoid receptor subtype-selective agonists induced IL-11 production. Treatment of animals with the EP4-specific agonist ONO-AE1-329 resulted in enhanced mucosal levels of IL-11, and increased IL-11 production by ex vivo cultured CMF. Modulation of cAMP levels produced diverging results, with enhancement of TGF-beta-induced IL-11 release in IMF pretreated with 8-Br-cAMP and inhibition in cells treated either with pertussis toxin or the PKA inhibitor H-89. These data suggest a physiological role for prostaglandins, MAPK signaling, and cAMP signaling for the production of myofibroblast-derived IL-11 in the mouse intestinal mucosa. PMID- 17332479 TI - Chronic intermittent hypoxia induces atherosclerosis. AB - RATIONALE: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established. OBJECTIVES: The objective of the present study was to examine whether CIH may induce atherosclerosis in C57BL/6J mice. METHODS: Forty male C57BL/6J mice, 8 weeks of age, were fed either a high cholesterol diet or a regular chow diet and subjected either to CIH or intermittent air (control conditions) for 12 weeks. MEASUREMENTS AND MAIN RESULTS: Nine of 10 mice simultaneously exposed to CIH and high-cholesterol diet developed atherosclerotic lesions in the aortic origin and descending aorta. In contrast, atherosclerosis was not observed in mice exposed to intermittent air and a high-cholesterol diet or in mice exposed to CIH and a regular diet. A high cholesterol diet resulted in significant increases in serum total and low-density lipoprotein cholesterol levels and a decrease in high-density lipoprotein cholesterol. Compared with mice exposed to intermittent air and a high cholesterol diet, combined exposure to CIH and a high-cholesterol diet resulted in marked progression of dyslipidemia with further increases in serum total cholesterol and low-density lipoprotein cholesterol (124 +/- 4 vs. 106 +/- 6 mg/dl; p < 0.05), a twofold increase in serum lipid peroxidation, and up regulation of an important hepatic enzyme of lipoprotein secretion, stearoyl coenzyme A desaturase-1. CONCLUSIONS: CIH causes atherosclerosis in the presence of diet-induced dyslipidemia. PMID- 17332480 TI - Cryptogenic hemoptysis: from a benign to a life-threatening pathologic vascular condition. AB - RATIONALE: Data on hemoptysis of unknown origin (i.e., "cryptogenic") are scarce and the outcome of patients affected is controversial. OBJECTIVES: To describe the clinical spectrum and course of patients with cryptogenic hemoptysis, as well as pathologic findings when surgery is performed. METHODS: A cohort of 81 patients referred for cryptogenic hemoptysis after clinical evaluation, chest radiography, fiberoptic bronchoscopy, and computed tomographic scan to a respiratory intermediate care and intensive care unit, from December 1995 to August 2004, with a prospective follow-up by visit or telephone interview. MEASUREMENTS AND MAIN RESULTS: The 81 patients (69 males) had a mean cumulative volume of hemoptysis averaging 190 ml on admission. First-line conservative measures and bronchial artery embolization controlled hemoptysis in 73 patients (90%). Emergency surgery was performed in six patients (7%) because of failure of bronchial artery embolization, and secondary surgery was scheduled in a seventh patient. A total of 73 patients were followed for a mean of 47 (+/- 35) months. No lung cancer developed. Hemoptysis recurred in 10 patients (4 within the first year; 6 between 1 and 8 yr later), 2 of whom underwent surgery. A specific bronchial vascular involvement (Dieulafoy disease) was demonstrated in five of the nine patients who had undergone surgery, especially in those with high amounts of bleeding. CONCLUSIONS: Cryptogenic hemoptysis may be a life threatening condition. Nonsurgical approaches provide immediate control of bleeding in most patients with cryptogenic hemoptysis, with few recurrences in both short and long terms. Dieulafoy disease of the bronchus, unsuspected after routine imaging investigations, may be involved in a subset of patients yet to be determined. PMID- 17332481 TI - Heritability of lung disease severity in cystic fibrosis. AB - RATIONALE: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. OBJECTIVES: To quantify the contribution of modifier genes to variation in CF lung disease severity. METHODS: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV(1) within the last year was used for cross-sectional analysis. FEV(1) measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (approximately 100% gene sharing) with that of dizygous (DZ) twins/siblings (approximately 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. MEASUREMENTS AND MAIN RESULTS: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82-0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50-0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). CONCLUSIONS: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID- 17332482 TI - Accumulation of dendritic cells and increased CCL20 levels in the airways of patients with chronic obstructive pulmonary disease. AB - RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. It is unclear if dendritic cells (DC) participate in this inflammatory process. OBJECTIVES: To evaluate the presence of DC in small airways of patients with COPD. METHODS: We evaluated DC infiltration in small airways by immunohistochemistry in patients with COPD (stage I-IV), never smokers, and smokers without COPD. Chemokine ligand 20 (CCL20, the most potent chemokine in attracting DC) was determined in total lung by RT-PCR and in induced sputum by enzyme-linked immunsorbent assay. Chemokine receptor 6 (CCR6, the receptor for CCL20) expression on human pulmonary DC was evaluated by RT-PCR and flow cytometry. MEASUREMENTS AND MAIN RESULTS: There is a significant increase in DC number in the epithelium (p = 0.007) and adventitia (p = 0.009) of small airways of patients with COPD compared with never-smokers and smokers without COPD. DC number in epithelium and adventitia increases along with disease severity. CCL20 mRNA expression in total lung and CCL20 protein levels in induced sputum are significantly higher in patients with COPD compared with never-smokers (p = 0.034 for CCL20 mRNA and p = 0.0008 for CCL20 protein) and smokers without COPD (p = 0.016 for CCL20 mRNA and p = 0.001 for CCL20 protein). DC isolated from human lung express CCR6 both at mRNA and at protein level. CONCLUSIONS: This is the first description of airway infiltration by DC in COPD. Moreover, interaction between CCL20 and CCR6 provides a possible mechanism for accumulation of DC in the lungs in COPD. PMID- 17332483 TI - Impairment of alveolar macrophage transcription in idiopathic pulmonary fibrosis. AB - RATIONALE: Alveolar macrophages are inflammatory cells that may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is characterized by excessive alveolar aggregation of cells and extracellular matrix proteins. OBJECTIVES: To identify potential molecular mechanisms of IPF. METHODS: To examine large-scale gene expression, messenger RNA isolated from alveolar macrophages and peripheral blood mononuclear cells from subjects with IPF and normal volunteers was hybridized to cDNA filters. MEASUREMENTS AND MAIN RESULTS: We showed that in IPF there is global down-regulation of gene expression in alveolar macrophages but not in blood monocytes. Nuclear run-on and pulse-chase studies showed that alveolar macrophages had significantly reduced transcription (p < 0.01). No significant difference in RNA degradation was found between subjects with IPF and normal volunteers. Western blot analyses revealed that concentrations of transcription factor II-H, a general transcription factor, were significantly lower in alveolar macrophages from subjects with IPF than in those from normal volunteers (p = 0.012). CONCLUSIONS: Impaired transcription in IPF is associated with decreased concentrations of transcription factor II-H in alveolar macrophages and may alter the intraalveolar milieu in IPF. PMID- 17332484 TI - Lung cells from neonates show a mesenchymal stem cell phenotype. AB - RATIONALE: Mesenchymal stem cells have been isolated from adult bone marrow, peripheral blood, adipose tissue, trabecular bone, articular synovium, and bronchial submucosa. OBJECTIVES: We hypothesized that the lungs of premature infants undergoing mechanical ventilation contain fibroblast-like cells with features of mesenchymal stem cells. METHODS: Tracheal aspirate fluid from mechanically ventilated, premature (< 30 wk gestation) infants 7 days old or younger was obtained from routine suctioning and plated on plastic culture dishes. MEASUREMENTS AND MAIN RESULTS: A total of 11 of 20 patients studied demonstrated fibroblast-like cells, which were identified as early as 6 hours after plating. Cells were found to express the mesenchymal stem cell markers STRO 1, CD73, CD90, CD105, and CD166, as well as CCR2b, CD13, prolyl 4-hydroxylase, and alpha-smooth muscle actin. Cells were negative for the hematopoietic and endothelial cell markers CD11b, CD31, CD34, or CD45. Tracheal aspirate monocyte chemoattractant protein-1/CCL2 levels were ninefold higher in aspirates in which fibroblast-like cells were found, and cells demonstrated chemotaxis in response to monocyte chemoattractant protein. Placement of cells into appropriate media resulted in adipogenic, osteogenic, and myofibroblastic differentiation. Patients from whom mesenchymal stem cells were isolated tended to require more days of mechanical ventilation and supplemental oxygen. CONCLUSIONS: Together, these data demonstrate that tracheal aspirate fluid from premature, mechanically ventilated infants contains fibroblasts with cell markers and differentiation potential typically found in mesenchymal stem cells. PMID- 17332485 TI - A worldwide perspective of atypical pathogens in community-acquired pneumonia. AB - RATIONALE: Controversy still exists in the international literature regarding the need to use antimicrobials covering atypical pathogens when initially treating hospitalized patients with community-acquired pneumonia (CAP). In different regions of the world, monotherapy with a beta-lactam antimicrobial is common. OBJECTIVES: We sought to correlate the incidence of CAP due to atypical pathogens in different regions of the world with the proportion of patients treated with an atypical regimen in those same regions. In addition, we sought to compare clinical outcomes of patients with CAP treated with and without atypical coverage. METHODS: A secondary analysis was performed using two comprehensive international databases. World regions were defined as North America (I), Europe (II), Latin America (III), and Asia and Africa (IV). Time to reach clinical stability, length of hospital stay, and mortality were compared between patients treated with and without atypical coverage. MEASUREMENTS AND MAIN RESULTS: The incidence of CAP due to atypical pathogens from 4,337 patients was 22, 28, 21, and 20% in regions I-IV, respectively. The proportion of patients treated with atypical coverage from 2,208 patients was 91, 74, 53, and 10% in regions I-IV, respectively. Patients treated with atypical coverage had decreased time to clinical stability (3.7 vs. 3.2 d, p < 0.001), decreased length of stay (7.1 vs. 6.1 d, p < 0.01), decreased total mortality (11.1 vs. 7%, p < 0.01), and decreased CAP-related mortality (6.4 vs. 3.8%, p = 0.05). CONCLUSIONS: The significant global presence of atypical pathogens and the better outcomes associated with antimicrobial regimens with atypical coverage support empiric therapy for all hospitalized patients with CAP with a regimen that covers atypical pathogens. PMID- 17332486 TI - Toll-like receptors 2-deficient mice are protected against postischemic coronary endothelial dysfunction. AB - OBJECTIVES: Toll-like receptors (TLR) 2 are expressed in cardiac and inflammatory cells, and regulate leukocyte function. Because leukocyte adhesion is a critical event in endothelial injury induced by ischemia/reperfusion (I/R), we assessed whether TLR2 were involved in I/R-induced coronary endothelial injury. METHODS AND RESULTS: Ischemia-reperfusion markedly decreased NO-mediated coronary relaxations to acetylcholine assessed ex vivo. In contrast, in TLR2 deficient mice, I/R paradoxically improved the NO-mediated responses to acetylcholine. To precise the cellular compartment expressing TLR2 which is involved in endothelial injury, we developed bone-marrow chimeric mice by transplanting TLR2-/- bone marrow to WT mice or WT bone marrow to TLR2-/- mice and submitted them to I/R 5 weeks after transplant. Both chimeric mice displayed similar protection as TLR2-/ mice against I/R-induced endothelial dysfunction, suggesting a role of TLR2 expressed on both non-bone marrow cells (in our case presumably endothelial cells and/or cardiomyocytes) and cells of bone marrow origin (presumably neutrophils). TLR2 deficiency was also associated with a smaller infarct size, and reduced reperfusion-induced production of reactive oxygen species and leukocyte infiltration. CONCLUSIONS: TLR2 contribute to coronary endothelial dysfunction after I/R, possibly through stimulation of neutrophil- (and free radical-) mediated endothelial injury. PMID- 17332487 TI - TRAF-1, -2, -3, -5, and -6 are induced in atherosclerotic plaques and differentially mediate proinflammatory functions of CD40L in endothelial cells. AB - OBJECTIVE: Several lines of evidence implicate CD40 ligand (CD40L, CD154) as a mediator and marker of atherosclerosis. This study investigated the involvement of tumor necrosis factor receptor-associated factors (TRAFs) in CD40 signaling in endothelial cells (ECs) and their expression in atheromata and cells involved in atherogenesis. METHODS AND RESULTS: CD40L enhanced the basal expression of TRAF 1, -2, -3, and 6, but not TRAF-5 in ECs. TRAFs associated with CD40 on ligation by CD40L. Study of ECs from TRAF-1, -2, and -5-deficient mice demonstrated functional involvement of TRAFs in proinflammatory CD40 signaling. Whereas TRAF-1 deficiency enhanced CD40L-induced IL-6 and MCP-1 expression, TRAF-2 and TRAF-5 deficiency inhibited CD40L-inducible IL-6 but not MCP-1 expression. Gene silencing in human ECs further delineated functions of TRAFs in CD40 signaling. TRAF-3 silencing in ECs showed increased CD40L-induced IL-6, MCP-1, and IL-8 expression, whereas TRAF-6 silencing increased selectively CD40L-induced MCP-1 expression. Enhanced TRAF levels in atherosclerotic lesions further supports involvement of members of this family of signaling molecules in arterial disease. CONCLUSIONS: These results implicate endothelial TRAF-1, -2, -3, -5, and -6 in CD40 signaling in atherogenesis, identifying these molecules as potential targets for selective therapeutic intervention. PMID- 17332488 TI - Circulating apoptotic progenitor cells: a novel biomarker in patients with acute coronary syndromes. AB - BACKGROUND: Progenitor CD34 cells are capable of differentiating into endothelial cells and play a role in neoangiogenesis. Circulating CD34+ cells and endothelial progenitor cells are increased in acute coronary syndrome (ACS) patients possibly because of peripheral mobilization. We tested the hypothesis that circulating apoptotic progenitors are detectable in healthy subjects and altered in ACS patients. METHODS AND RESULTS: Peripheral blood mononuclear cells were isolated by Ficoll density gradient from 53 patients with ACS undergoing coronary angiography and 27 healthy subjects. Apoptosis in progenitor CD34+ cells was assessed using the Annexin V-PE/7-AAD detection kit, and fluorescence-activated cell sorter analysis was performed with triple staining for CD34, annexin-V, and 7-AAD. The percentage of apoptotic CD34+ progenitors was determined in the 2 subject groups and correlated with clinical characteristics. The percentage of apoptotic CD34+ progenitor cells was significantly increased in patients with ACS as compared with healthy subjects and was associated with the extent of coronary stenosis by angiography. There was no significant correlation between apoptotic progenitor CD34+ cells and the other parameters that we examined (age, smoking, hypertension, hyperlipidemia, diabetes mellitus, ejection fraction, creatinine levels, or taking any of the various medications, including beta blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium blockers, nitrates, or statins). CONCLUSION: We established for the first time to our knowledge an assay to detect circulating apoptotic progenitor cells using fluorescein isothiocyanate-anti-CD34 MAb, annexin V-PE, and 7-AAD and found that apoptotic CD34+ cells are increased in ACS patients and in patients with more extensive coronary artery disease. This novel assay may shed new light on the factors governing the hemostasis of progenitor CD34+ cells. PMID- 17332489 TI - Smooth muscle-targeted knockout of connexin43 enhances neointimal formation in response to vascular injury. AB - OBJECTIVE: Vascular disease alters and reduces connexin expression and a reduction in connexin 43 (Cx43) expression diminishes the extent of atherosclerosis observed in a high-cholesterol diet murine model. We hypothesized that connexins might play a role in the smooth muscle cell response to vascular injury. METHODS AND RESULTS: We therefore studied a line of smooth muscle cell specific, Cx43 gene knockout mice (SM Cx43 KO) in which the carotid arteries were injured, either by vascular occlusion or by a wire injury. In the SM Cx43 KO mice both types of injury manifested accelerated growth of the neointima and of the adventitia. Isolated vascular smooth muscle cells from the SM Cx43 KO mice grew at a slightly faster rate in culture, and to marginally higher saturation densities than those of control mice, but these changes were not adequate to explain the large changes in the injured vessels. CONCLUSIONS: These observations provide direct evidence that smooth muscle Cx43 gap junctions play a multi faceted role in modulating the in vivo growth response of vascular smooth muscle cells to vascular injury. PMID- 17332490 TI - A secreted soluble form of LR11, specifically expressed in intimal smooth muscle cells, accelerates formation of lipid-laden macrophages. AB - OBJECTIVE: Macrophages play a key role in lipid-rich unstable plaque formation and interact with intimal smooth muscle cells (SMCs) in early and progressive stages of atherosclerosis. LR11 (also called sorLA), a member of low-density lipoprotein receptor family, is highly and specifically expressed in intimal SMCs, and causes urokinase-type plasminogen activator receptor-mediated degradation of extracellular matrices. Here we investigated whether the secreted soluble form of LR11 (solLR11) enhances adhesion, migration, and lipid accumulation in macrophages using animal models and cultured systems. METHODS AND RESULTS: Immunohistochemistry showed solLR11 expression in thickened intima of balloon-denuded rat artery. Macrophage infiltration into the cuff-injured artery was markedly reduced in LR11-deficient mice. In vitro functional assays using THP 1-derived macrophages showed that solLR11 (1 microg/mL) significantly increased acetylated low-density lipoprotein uptake by THP-1 cells and cell surface levels of scavenger receptor SR-A 1.7- and 2.8-fold, respectively. SolLR11 dose dependently increased the migration activity of THP-1 macrophages and adhesion to extracellular matrices 2.0- and 2.1-fold, respectively, at 1 microg/mL. These effects of solLR11 were almost completely inhibited by a neutralizing anti urokinase-type plasminogen activator receptor antibody. CONCLUSION: SolLR11, secreted from intimal SMCs, regulates adhesion, migration, and lipid accumulation in macrophages through activation of urokinase-type plasminogen activator receptor. The formation of lipid-laden macrophages in atherosclerotic plaques possibly is regulated by SolLR11 of intimal SMCs. PMID- 17332491 TI - Physiological roles of vascular nucleoside transporters. AB - Nucleoside transporters (NTs) comprise 2 widely expressed families, the equilibrative nucleoside transporters (diffusion-limited channels) and concentrative nucleoside transporters (sodium-dependent transporters). Because of their anatomic position at the blood-tissue interface, vascular NTs are in an ideal position to influence vascular nucleoside levels, particularly adenosine, which among others plays an important role in tissue protection during acute injury. For example, endothelial NTs contribute to preserving the vascular integrity during conditions of limited oxygen availability (hypoxia). Indeed, hypoxia-inducible factor-1-dependent repression of NTs results in enhanced extracellular adenosine signaling and thus attenuates hypoxia-associated increases in vascular leakage. In addition, vascular NTs also contribute to cardiac ischemic preconditioning, coronary vasodilation, and inhibition of platelet aggregation. Moreover, vascular nucleoside uptake via NTs is important for nucleoside recovery, particularly in cells lacking de novo nucleotide synthesis pathways (erythrocytes, leukocytes). Taken together, vascular NTs are critical in modulating adenosine-mediated responses during conditions such as inflammation or hypoxia. PMID- 17332492 TI - Assessment of unstable atherosclerosis in mice. AB - There is an urgent need for representative animal models where prospective examination of the events leading up to plaque rupture and the rupture process itself can be performed. Recently, reports have begun to emerge that apolipoprotein E and low density lipoprotein receptor knockout mice may spontaneously develop unstable atherosclerosis, with plaques in certain parts of the arterial tree showing features suggestive of plaque rupture. Here we discuss the problems inherent in applying definitions of plaque rupture as seen in human arteries to mice; the anatomic locations in mice where unstable plaques do and do not occur; methods of inducing plaque instability in mice; and how to assess plaque stability in mice. These considerations lead us to a number of general recommendations. PMID- 17332493 TI - Plaque rupture in humans and mice. AB - Despite the many studies of murine atherosclerosis, we do not yet know the relevance of the natural history of this model to the final events precipitated by plaque disruption of human atherosclerotic lesions. The literature has become particularly confused because of the common use of terms such as "instability", "vulnerable", "rupture", or even "thrombosis" for features of plaques in murine model systems not yet shown to rupture spontaneously and in an animal surprisingly resistant to formation of thrombi at sites of atherosclerosis. We suggest that use of conclusory terms like "vulnerable" and "stable" should be discouraged. Similarly, terms such as "buried fibrous caps" that imply preceding events that are unproven tend to create confusion. We will argue that such terminology may mislead readers by implying knowledge that does not yet exist. We suggest, instead, a focus on specific processes that various forms of data have implicated in plaque progression. For example, formation of the fibrous cap, protease activation, and cell death in the necrotic core can be well described and have all been modeled in well-defined experiments. The relevance of such well defined, objective, descriptive observations in the mouse can be tested for relevance against data from human pathology. PMID- 17332496 TI - Formation of cysts by alveolar type II cells in three-dimensional culture reveals a novel mechanism for epithelial morphogenesis. AB - Many organs consist of a hollow cavity surrounded by a monolayer of epithelial cells. Despite their common structure, such organs form by diverse morphogenetic processes. Three-dimensional culture systems have been useful in analyzing the events. Most processes require a combination of cell proliferation and cell death to produce a hollow cavity. Here, we describe a new three-dimensional culture system in which primary human lung alveolar type II cells formed hollow epithelial cysts by a novel process. Individual cells moved, collided, and formed alveolar-like cysts without appreciable proliferation or apoptosis. The alveolar like cysts consisted of a polarized monolayer of differentiated alveolar type II cells, which secreted surfactant into the central lumen. Blockage of beta1 integrin did not alter cell movement or collision, but it greatly reduced adhesion of cells after collision and subsequent formation of alveolar-like cysts. Treatment of preformed alveolar-like cysts with forskolin increased their diameter, possibly due to stimulation of fluid secretion into the lumen. We conclude that epithelial differentiation and cyst formation can occur without appreciable proliferation or apoptosis. PMID- 17332497 TI - The MAGUK protein MPP7 binds to the polarity protein hDlg1 and facilitates epithelial tight junction formation. AB - Three groups of evolutionarily conserved proteins have been implicated in the establishment of epithelial cell polarity: the apically-localized proteins of the Par (Par3-Par6-aPKC-Cdc42) and Crumbs groups (Crb3-PALS1-PATJ) and the basolaterally localized proteins of the Dlg group (Dlg1-Scribble-Lgl). During epithelial morphogenesis, these proteins participate in a complex network of interdependent interactions that define the position and functional organization of adherens junctions and tight junctions. However, the biochemical pathways through which they control polarity are poorly understood. In this study, we identify an interaction between endogenous hDlg1 and MPP7, a previously uncharacterized MAGUK-p55 subfamily member. We find that MPP7 targets to the lateral surface of epithelial cells via its L27N domain, through an interaction with hDlg1. Loss of either hDlg1 or MPP7 from epithelial Caco-2 cells results in a significant defect in the assembly and maintenance of functional tight junctions. We conclude that the formation of a complex between hDlg1 and MPP7 promotes epithelial cell polarity and tight junction formation. PMID- 17332498 TI - Modulation of cell cycle-specific gene expressions at the onset of S phase arrest contributes to the robust DNA replication checkpoint response in fission yeast. AB - Fission yeast replication checkpoint kinases Rad3p and Cds1p are essential for maintaining cell viability after transient treatment with hydroxyurea (HU), an agent that blocks DNA replication. Although current studies have focused on the cyclin-dependent protein kinase Cdc2p that is regulated by these checkpoint kinases, other aspects of their functions at the onset of S phase arrest have not been fully understood. In this study, we use genome-wide DNA microarray analyses to show that HU-induced change of expression profiles in synchronized G(2) cells occurs specifically at the onset of S phase arrest. Induction of many core environmental stress response genes and repression of ribosomal genes happen during S phase arrest. Significantly, peak expression level of the MluI-like cell cycle box (MCB)-cluster (G(1)) genes is maintained at the onset of S phase arrest in a Rad3p- and Cds1p-dependent manner. Expression level maintenance of the MCB cluster is mediated through the accumulation of Rep2p, a putative transcriptional activator of the MBF complex. Conversely, the FKH-cluster (M) genes are repressed during the onset of S phase arrest in a Rad3p-dependent manner. Repression of the FKH-cluster genes is mediated through the decreased levels of one of the putative forkhead transcription factors, Sep1p, but not Fkh2p. Together, our results demonstrate that Rad3p and Cds1p modulate transcriptional response during the onset of S phase arrest. PMID- 17332499 TI - Direct binding to Rsp5p regulates ubiquitination-independent vacuolar transport of Sna3p. AB - The sorting of integral membrane proteins such as carboxypeptidase S (Cps1p) into the luminal vesicles of multivesicular bodies (MVBs) in Saccharomyces cerevisiae requires ubiquitination of their cytosolic domains by the ubiquitin ligases Rsp5p and/or Tul1p. An exception is Sna3p, which does not require ubiquitination for entry into MVBs. The mechanism underlying this ubiquitination-independent MVB sorting pathway has not yet been characterized. Here, we show that Sna3p sorting into the MVB pathway depends on a direct interaction between a PPAY motif within its C-terminal cytosolic tail and the WW domains of Rsp5p. Disruption of this interaction inhibits vacuolar targeting of Sna3p and causes its accumulation in a compartment that overlaps only partially with MVBs. Surprisingly, Sna3p does require a functional ubiquitin-ligase HECT domain within Rsp5p; however, the dependence of Sna3p on HECT domain activity is distinct from that of Cps1p. Last, we show that Sna3p requires neither Tul1p nor the transmembrane adaptor protein Bsd2p for its MVB sorting. Our data demonstrate that Sna3p follows a novel ubiquitination-independent, but Rsp5p-mediated, sorting pathway to the vacuole. PMID- 17332500 TI - Diverse cytopathologies in mitochondrial disease are caused by AMP-activated protein kinase signaling. AB - The complex cytopathology of mitochondrial diseases is usually attributed to insufficient ATP. AMP-activated protein kinase (AMPK) is a highly sensitive cellular energy sensor that is stimulated by ATP-depleting stresses. By antisense inhibiting chaperonin 60 expression, we produced mitochondrially diseased strains with gene dose-dependent defects in phototaxis, growth, and multicellular morphogenesis. Mitochondrial disease was phenocopied in a gene dose-dependent manner by overexpressing a constitutively active AMPK alpha subunit (AMPKalphaT). The aberrant phenotypes in mitochondrially diseased strains were suppressed completely by antisense-inhibiting AMPKalpha expression. Phagocytosis and macropinocytosis, although energy consuming, were unaffected by mitochondrial disease and AMPKalpha expression levels. Consistent with the role of AMPK in energy homeostasis, mitochondrial "mass" and ATP levels were reduced by AMPKalpha antisense inhibition and increased by AMPKalphaT overexpression, but they were near normal in mitochondrially diseased cells. We also found that 5 aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, a pharmacological AMPK activator in mammalian cells, mimics mitochondrial disease in impairing Dictyostelium phototaxis and that AMPKalpha antisense-inhibited cells were resistant to this effect. The results show that diverse cytopathologies in Dictyostelium mitochondrial disease are caused by chronic AMPK signaling not by insufficient ATP. PMID- 17332501 TI - Troyer syndrome protein spartin is mono-ubiquitinated and functions in EGF receptor trafficking. AB - Troyer syndrome is an autosomal recessive hereditary spastic paraplegia caused by mutation in the spartin (SPG20) gene, which encodes a widely expressed protein of unknown function. This mutation results in premature protein truncation and thus might signify a loss-of-function disease mechanism. In this study, we have found that spartin is mono-ubiquitinated and functions in degradation of the epidermal growth factor receptor (EGFR). Upon EGF stimulation, spartin translocates from the cytoplasm to the plasma membrane and colocalizes with internalized EGF-Alexa. Knockdown of spartin by small interfering RNA decreases the rate of EGFR degradation and also affects EGFR internalization, recycling, or both. Furthermore, overexpression of spartin results in a prominent decrease in EGFR degradation. Taken together, our data suggest that spartin is involved in the intracellular trafficking of EGFR and that impaired endocytosis may underlie the pathogenesis of Troyer syndrome. PMID- 17332502 TI - The cytoskeleton-associated PDZ-LIM protein, ALP, acts on serum response factor activity to regulate muscle differentiation. AB - In this report, an antisense RNA strategy has allowed us to show that disruption of ALP expression affects the expression of the muscle transcription factors myogenin and MyoD, resulting in the inhibition of muscle differentiation. Introduction of a MyoD expression construct into ALP-antisense cells is sufficient to restore the capacity of the cells to differentiate, illustrating that ALP function occurs upstream of MyoD. It is known that MyoD is under the control of serum response factor (SRF), a transcriptional regulator whose activity is modulated by actin dynamics. A dramatic reduction of actin filament bundles is observed in ALP-antisense cells and treatment of these cells with the actin-stabilizing drug jasplakinolide stimulates SRF activity and restores the capacity of the cells to differentiate. Furthermore, we show that modulation of ALP expression influences SRF activity, the level of its coactivator, MAL, and muscle differentiation. Collectively, these results suggest a critical role of ALP on muscle differentiation, likely via cytoskeletal regulation of SRF. PMID- 17332503 TI - M-cadherin activates Rac1 GTPase through the Rho-GEF trio during myoblast fusion. AB - Cadherins are transmembrane glycoproteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion and play crucial role during skeletal myogenesis. M cadherin is required for myoblast fusion into myotubes, but its mechanisms of action remain unknown. The goal of this study was to cast some light on the nature of the M-cadherin-mediated signals involved in myoblast fusion into myotubes. We found that the Rac1 GTPase activity is increased at the time of myoblast fusion and it is required for this process. Moreover, we showed that M cadherin-dependent adhesion activates Rac1 and demonstrated the formation of a multiproteic complex containing M-cadherin, the Rho-GEF Trio, and Rac1 at the onset of myoblast fusion. Interestingly, Trio knockdown efficiently blocked both the increase in Rac1-GTP levels, observed after M-cadherin-dependent contact formation, and myoblast fusion. We conclude that M-cadherin-dependent adhesion can activate Rac1 via the Rho-GEF Trio at the time of myoblast fusion. PMID- 17332504 TI - Dynamic regulation of p53 subnuclear localization and senescence by MORC3. AB - The tumor suppressor p53 is a key transcriptional factor regulating the induction of cellular senescence by oncogenic signals. The activity of p53 is regulated by recruitment into promyelocytic leukemia (PML)-nuclear bodies (NBs) as well as by stabilization through posttranslational modifications such as phosphorylation and acetylation. Here we found that MORC3 (microrchidia3)-ATPase activated p53 and induced cellular senescence in normal human and mouse fibroblasts but not p53-/- fibroblasts. Conversely, genotoxic stress-induced phosphorylation and stabilization of p53 but barely increased its transcriptional activity in Morc3-/ fibroblasts. MORC3 localized on PML-NBs in presence of PML and mediated recruitment of p53 and CREB-binding protein (CBP) into PML-NBs. In contrast, expression of ATPase activity-deficient mutant MORC3-E35A or siRNA repression of MORC3 impaired the localization of p53 and Sp100 but not CBP on PML-NBs. These results suggest that MORC3 regulates p53 activity and localization into PML-NBs. We identified a new molecular mechanism that regulates the activity of nuclear proteins by localization to a nuclear subdomain. PMID- 17332505 TI - A bipartite signal regulates the faithful delivery of apical domain marker podocalyxin/Gp135. AB - Podocalyxin/Gp135 was recently demonstrated to participate in the formation of a preapical complex to set up initial polarity in MDCK cells, a function presumably depending on the apical targeting of Gp135. We show that correct apical sorting of Gp135 depends on a bipartite signal composed of an extracellular O glycosylation-rich region and the intracellular PDZ domain-binding motif. The function of this PDZ-binding motif could be substituted with a fusion construct of Gp135 with Ezrin-binding phosphoprotein 50 (EBP50). In accordance with this observation, EBP50 binds to newly synthesized Gp135 at the Golgi apparatus and facilitates oligomerization and sorting of Gp135 into a clustering complex. A defective connection between Gp135 and EBP50 or EBP50 knockdown results in a delayed exit from the detergent-resistant microdomain, failure of oligomerization, and basolateral missorting of Gp135. Furthermore, the basolaterally missorted EBP50-binding defective mutant of Gp135 was rapidly retrieved via a PKC-dependent mechanism. According to these findings, we propose a model by which a highly negative charged transmembrane protein could be packed into an apical sorting platform with the aid of its cytoplasmic partner EBP50. PMID- 17332507 TI - Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. AB - Human umbilical cord perivascular cells (HUCPVCs) have been shown to have a high proliferative potential and the capacity to differentiate into an osteogenic phenotype. HUCPVCs have thus been considered a possible extra-embryonic mesenchymal stem cell (MSC) source for cell-based therapies. To assess this potential, we compared HUCPVCs to the "gold standard" bone marrow mesenchymal stromal cells (BMSCs) with respect to their proliferation, differentiation, and transfection capacities. HUCPVCs showed a higher proliferative potential than BMSCs and were capable of osteogenic, chondrogenic, and adipogenic differentiation. Interestingly, osteogenic differentiation of HUCPVCs proceeded more rapidly than BMSCs. Additionally, HUCPVCs expressed higher levels of CD146, a putative MSC marker, relative to BMSCs. HUCPVCs showed comparable transfection efficiency as BMSCs using a nucleofection method but were more amenable to transfection with liposomal methods (FuGENE). Gene array analysis showed that HUCPVCs also expressed Wnt signaling pathway genes that have been implicated in the regulation of MSCs. The similar characteristics between HUCPVCs and MSCs support the applicability of HUCPVCs for cell-based therapies. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17332506 TI - The NHERF1 PDZ2 domain regulates PKA-RhoA-p38-mediated NHE1 activation and invasion in breast tumor cells. AB - Understanding the signal transduction systems governing invasion is fundamental for the design of therapeutic strategies against metastasis. Na(+)/H(+) exchanger regulatory factor (NHERF1) is a postsynaptic density 95/disc-large/zona occludens (PDZ) domain-containing protein that recruits membrane receptors/transporters and cytoplasmic signaling proteins into functional complexes. NHERF1 expression is altered in breast cancer, but its effective role in mammary carcinogenesis remains undefined. We report here that NHERF1 overexpression in human breast tumor biopsies is associated with metastatic progression, poor prognosis, and hypoxia-inducible factor-1alpha expression. In cultured tumor cells, hypoxia and serum deprivation increase NHERF1 expression, promote the formation of leading edge pseudopodia, and redistribute NHERF1 to these pseudopodia. This pseudopodial localization of NHERF1 was verified in breast biopsies and in three-dimensional Matrigel culture. Furthermore, serum deprivation and hypoxia stimulate the Na(+)/H(+) exchanger, invasion, and activate a protein kinase A (PKA)-gated RhoA/p38 invasion signal module. Significantly, NHERF1 overexpression was sufficient to induce these morphological and functional changes, and it potentiated their induction by serum deprivation. Functional experiments with truncated and binding groove-mutated PDZ domain constructs demonstrated that NHERF1 regulates these processes through its PDZ2 domain. We conclude that NHERF1 overexpression enhances the invasive phenotype in breast cancer cells, both alone and in synergy with exposure to the tumor microenvironment, via the coordination of PKA-gated RhoA/p38 signaling. PMID- 17332508 TI - Directed neural differentiation of human embryonic stem cells via an obligated primitive anterior stage. AB - Understanding neuroectoderm formation and subsequent diversification to functional neural subtypes remains elusive. We show here that human embryonic stem cells (hESCs) differentiate to primitive neuroectoderm after 8-10 days. At this stage, cells uniformly exhibit columnar morphology and express neural markers, including anterior but not posterior homeodomain proteins. The anterior identity of these cells develops regardless of morphogens present during initial neuroectoderm specification. This anterior phenotype can be maintained or transformed to a caudal fate with specific morphogens over the next week, when cells become definitive neuroepithelia, marked by neural tube-like structures with distinct adhesion molecule expression, Sox1 expression, and a resistance to additional patterning signals. Thus, primitive neuroepithelia represents the earliest neural cells that possess the potential to differentiate to regionally specific neural progenitors. This finding offers insights into early human brain development and lays a foundation for generating neural cells with correct positional and transmitter profiles. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17332509 TI - Spontaneous transformation of human adult nontumorigenic stem cells to cancer stem cells is driven by genomic instability in a human model of glioblastoma. AB - The presence of a CD133+/nestin+ population in brain tumors suggests that a normal neural stem cell may be the cell of origin for gliomas. We have identified human CD133-positive NSCs from adult glioma tissue and established them as long term in vitro cultures human neuroglial culture (HNGC)-1. Replicative senescence in HNGC-1 led to a high level of genomic instability and emergence of a spontaneously immortalized clone that developed into cell line HNGC-2 with features of cancer stem cells (CSCs), which include the ability for self-renewal and the capacity to form CD133-positive neurospheres and develop intracranial tumors. The data from our study specify an important role of genomic instability in initiation of transformed state as well as its progression into highly tumorigenic CSCs. The activated forms of Notch and Hes isoforms were expressed in both non-neoplastic neural stem cells and brain tumor stem cells derived from it. Importantly, a significant overexpression of these molecules was found in the brain tumor stem cells. These findings suggest that this model comprised of HNGC 1 and HNGC-2 cells would be a useful system for studying pathways involved in self-renewal of stem cells and their transformation to cancer stem cells. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17332510 TI - Epidermal growth factor signaling mediated by grb2 associated binder1 is required for the spatiotemporally regulated proliferation of olig2-expressing progenitors in the embryonic spinal cord. AB - Gab1 (Grb2 associated binder1) has been identified as an adaptor molecule downstream of many growth factors, including epidermal growth factor (EGF), fibroblast growth factor, and platelet-derived growth factor, which have been shown to play crucial roles as mitotic signals for a variety of neural progenitor cells, including stem cells, both in vitro and in vivo. Here, we show that Gab1 deficiency results in a reduction in the number of Olig2-positive (Olig2(+)) progenitor cells in the developing mouse spinal cord after embryonic day 12.5 (E12.5), when gliogenesis starts in the pMN domain where the EGF receptor (EGFR) is expressed predominantly. Our in vitro analysis further revealed that Gab1 is essential for EGF-dependent proliferation of Olig2(+) progenitor cells derived from the E12.5 ventral and E14.5 dorsal but not ventral spinal cord, whereas Gab1 is always required for the activation of Akt1 but not of ERK1/2. Moreover, we found that the action of the Gab1/Akt pathway is context-dependent, since constitutively active Akt1 could rescue the proliferation defect only in the E12.5 spinal cord of the Gab1-deficient mouse in vitro. Finally, we demonstrated that EGFR-deficient mice and Gab1-deficient mice showed a similar reduction in the number of Olig2(+) progenitor cells in the developing spinal cord. These findings indicate that EGFR-mediated signaling through Gab1/Akt contributes to the sufficient expansion of Olig2(+) progenitor cells in a spatiotemporally regulated manner, which represents the origin of glial cells in the developing spinal cord. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17332511 TI - Characterization of the limbal epithelial stem cell niche: novel imaging techniques permit in vivo observation and targeted biopsy of limbal epithelial stem cells. AB - It is anticipated that stem cell (SC) therapy will enable the regeneration of diseased tissues and organs. Understanding SC niches is an essential step toward realizing this goal. By virtue of its optical transparency and physical separation of SC and transient amplifying cell compartments, the human cornea provides a unique opportunity to visualize and observe a population of adult stem cells, limbal epithelial stem cells (LESCs), in their niche environment. To date, the characteristics of the LESC niche have remained unclear. State-of-the-art imaging techniques were used to construct a three-dimensional (3D) view of the entire human corneal limbus and identify the structural characteristics of the LESC niche. Two distinct candidate LESC niche structures were identified. Cells within these structures express high levels of the putative limbal stem cell markers p63alpha and ABCG2; however, current methods cannot identify for certain which exact cells within this cell population are truly LESCs. These structures could be located and observed in vivo in normal human subjects, but not in patients with clinically diagnosed corneal LESC deficiency. The distribution of these structures around the corneal circumference is not uniform. Biopsies targeted to limbal regions rich in LESC niche structures yielded significantly higher numbers of LESCs in culture. Our findings demonstrate how adult stem cell niches can be identified and observed in vivo in humans and provide new biological insight into the importance of LESC niche structures in maintaining normal LESC function. Finally, the concept of targeted biopsy of adult SC niches improves stem cell yield and may prove to be essential for the successful development of novel adult stem cell therapies. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17332512 TI - Identification of high proliferative potential precursors with hemangioblastic activity in the mouse aorta-gonad- mesonephros region. AB - Hemangioblast, a precursor possessing hematopoietic and endothelial potential, is identified as the blast colony-forming cell in the murine gastrulating embryos (E7.0-E7.5). Whether hemangioblast exists in the somite-stage embryos is unknown, even though hemogenic endothelium is regarded as the precursor of definitive hematopoiesis in the aorta-gonad-mesonephros (AGM) region. To address the issue, we developed a unique three-step assay of high proliferative potential (HPP) precursors. The AGM region contained a kind of HPP precursor that displayed hematopoietic self-renewal capacity and was able to differentiate into functional endothelial cells in vitro (i.e., incorporating DiI-acetylated low-density lipoprotein, expressing von Willebrand factors, and forming network structures in Matrigel). The clonal nature was verified by cell mixing assay. However, the bilineage precursor with high proliferative potential-the HPP-hemangioblast (HA) was not readily detected in the yolk sac (E8.25-E12.5), embryonic circulation (E10.5), placenta (E10.5-E11.5), fetal liver (E11.5-E12.5), and even umbilical artery (E11.5), reflective of its strictly spatial-regulated ontogeny. Expression of CD45, a panhematopoietic marker, distinguished hematopoietic-restricted HPP colony-forming cell from the bipotential HPP-HA. Finally, we revealed that basic fibroblast growth factor, other than vascular endothelial growth factor or transforming growth factor-beta1, was a positive modulator of the HPP-HA proliferation. Taken together, the HPP-HA represents a novel model for definitive hemangioblast in the mouse AGM region and will shed light on molecular mechanisms underlying the hemangioblast development. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17332513 TI - Optimized flow cytometric analysis of central nervous system tissue reveals novel functional relationships among cells expressing CD133, CD15, and CD24. AB - Although flow cytometry is useful for studying neural lineage relationships, the method of dissociation can potentially bias cell analysis. We compared dissociation methods on viability and antigen recognition of mouse central nervous system (CNS) tissue and human CNS tumor tissue. Although nonenzymatic dissociation yielded poor viability, papain, purified trypsin replacement (TrypLE), and two purified collagenase/neutral protease cocktails (Liberase-1 or Accutase) each efficiently dissociated fetal tissue and postnatal tissue. Mouse cells dissociated with Liberase-1 were titrated with antibodies identifying distinct CNS precursor subtypes, including CD133, CD15, CD24, A2B5, and PSA-NCAM. Of the enzymes tested, papain most aggressively reduced antigenicity for mouse and human CD24. On human CNS tumor cells, CD133 expression remained highest after Liberase-1 and was lowest after papain or Accutase treatment; Liberase-1 digestion allowed magnetic sorting for CD133 without the need for an antigen re expression recovery period. We conclude that Liberase-1 and TrypLE provide the best balance of dissociation efficiency, viability, and antigen retention. One implication of this comparison was confirmed by dissociating E13.5 mouse cortical cells and performing prospective isolation and clonal analysis on the basis of CD133/CD24 or CD15/CD24 expression. Highest fetal expression of CD133 or CD15 occurred in a CD24(hi) population that was enriched in neuronal progenitors. Multipotent cells expressed CD133 and CD15 at lower levels than did these neuronal progenitors. We conclude that CD133 and CD15 can be used similarly as selectable markers, but CD24 coexpression helps to distinguish fetal mouse multipotent stem cells from neuronal progenitors and postmitotic neurons. This particular discrimination is not possible after papain treatment. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17332514 TI - Cell-cell and cell-extracellular matrix interactions regulate embryonic stem cell differentiation. AB - Cell interactions with the extracellular matrix (ECM) play a critical role in their physiology. Here, we sought to determine the role of exogenous and endogenous ECM in the differentiation of nonhuman primate ESCs. We evaluated cell differentiation from expression of lineage gene mRNA and proteins using real-time polymerase chain reaction and immunohistochemistry. We found that ESCs that attached to and spread upon highly adhesive collagen do not differentiate efficiently, whereas on the less adhesive Matrigel, ESCs form aggregates and differentiate along mesoderm and especially endoderm lineages. To further decrease ESC attachment to the substrate, we cultured them either on nonadhesive agarose or in suspension. In both cases, ESCs formed aggregates and efficiently differentiated along endoderm and mesoderm lineages, most strikingly into cardiomyocytes. Aggregates formed by thus-differentiated ESCs started to beat with a frequency of 50-100 beats per minute and continued to beat for approximately a month. In spite of the presence of exogenous ECM, ESCs were dependent on endogenous ECM for their survival and differentiation, as the inhibition of endogenous collagen induced a gradual loss of ESCs and neither a simple matrix, such as type I collagen, nor the complex matrix Matrigel was able to rescue these cells. In conclusion, adhesiveness to various ECM and nonbiological substrates determines the differentiation of ESCs in such a way that efficient cell-cell aggregation, together with less efficient cell attachment and spreading, results in more efficient cell differentiation. PMID- 17332515 TI - Stem cell activity of human side population and alpha6 integrin-bright keratinocytes defined by a quantitative in vivo assay. AB - The isolation and characterization of living human epithelial stem cells is difficult because distinguishing cell surface markers have not been identified with certainty. Side population keratinocytes (SP-KCs) that efflux Hoechst 33342 fluorescent dye, analogous to bone marrow-derived side population (SP) hematopoietic stem cells, have been identified in human skin, but their potential to function as keratinocyte stem cells (KSCs) in vivo is not known. On the other hand, human keratinocyte populations that express elevated levels of beta1 and alpha6 integrins and are distinct from SP-KCs, which express low levels of integrins, may be enriched for KSCs based on reported results of in vitro cell culture assays. When in vitro assays were used to measure total cell output of human SP-KCs and integrin-bright keratinocytes, we could not document their superior long-term proliferative activity versus unfractionated keratinocytes. To further assess the KSC characteristics in SP-KCs and integrin-bright keratinocytes, we used an in vivo competitive repopulation assay in which bioengineered human epidermis containing competing keratinocyte populations with different human major histocompatibility (MHC) class I antigens were grafted onto immunocompromised mice, and the intrinsic MHC class I antigens are used to quantify expansion of competing populations. In these in vivo studies, human SP KCs showed little competitive expansion in vivo and were not enriched for KSCs. In contrast, keratinocytes expressing elevated levels of alpha6 integrin and low levels of CD71 (alpha6-bright/CD71-dim) expanded over 200-fold during the 33-week in vivo study. These results definitively demonstrate that human alpha6 bright/CD71-dim keratinocytes are enriched with KSCs, whereas SP-KCs are not. PMID- 17332516 TI - Amino acids, taste circuits, and feeding behavior in Drosophila: towards understanding the psychology of feeding in flies and man. AB - Feeding can be regulated by a variety of external sensory stimuli such as olfaction and gustation, as well as by systemic internal signals of feeding status and metabolic needs. Faced with a major health epidemic in eating-related conditions, such as obesity and diabetes, there is an ever increasing need to dissect and understand the complex regulatory network underlying the multiple aspects of feeding behavior. In this minireview, we highlight the use of Drosophila in studying the neural circuits that control the feeding behavior in response to external and internal signals. In particular, we outline the work on the neuroanatomical and functional characterization of the newly identified hugin neuronal circuit. We focus on the pivotal role of the central nervous system in integrating external and internal feeding-relevant information, thus enabling the organism to make one of the most basic decisions - to eat or not to eat. PMID- 17332517 TI - Evidence that the preovulatory rise in intrafollicular progesterone may not be required for ovulation in cattle. AB - Despite ample evidence pointing to an obligatory involvement of progesterone in ovulation, the mechanisms responsible for the ovulation promoting effects of intrafollicular progesterone are unclear. The objectives of this study were to determine if ovulation, luteinization and the gonadotropin surge-induced regulation of select extracellular matrix-degrading enzymes and their inhibitors, and mRNAs for prostaglandin (PG) biosynthesis and metabolizing enzymes are blocked following suppression of the intrafollicular increase in progesterone. Bovine preovulatory follicles were injected with the 3 beta-hydroxysteroid dehydrogenase inhibitor trilostane or diluent and collected at 0, 12, and 24 h after GnRH induction of the preovulatory LH surge. Intrafollicular trilostane administration blocked the preovulatory increase in follicular fluid progesterone resulting in concentrations similar to those observed at time 0 post-GnRH injection. The preovulatory increase in follicular fluid PGE(2) and PGF(2alpha) was reduced in trilostane-treated follicles and accompanied by upregulation of prostaglandin dehydrogenase mRNA in the granulosal and thecal cells. However, follicle rupture was not blocked by inhibition of the preovulatory rise in intrafollicular progesterone, and normal serum progesterone concentrations were observed during subsequent luteal development. Effects of trilostane administration on preovulatory changes in mRNA abundance and protein/activity in preovulatory follicles for most regulators of extracellular matrix remodeling examined were distinct from changes previously observed following the inhibition of intrafollicular prostaglandin synthesis. Results suggest that the preovulatory increase in intrafollicular progesterone may not be obligatory for bovine follicle rupture, luteinization, or regulation of prominent matrix-degrading proteinases and their inhibitors associated with ovulation. PMID- 17332518 TI - Oxidative stress increases placental and endothelial cell activin A secretion. AB - Circulating levels of activin A are significantly increased in women with preeclampsia when compared with those with a normal pregnancy. The mechanisms underlying these increased levels are unknown. We undertook these studies to explore whether oxidative stress might be the mechanism. We exposed trophoblast explants, human umbilical vein endothelial cells (HUVECs) and peripheral blood monocytes to oxidative stress in vitro using xanthine/xanthine oxidase (X/XO), measuring activin A and isoprostane in conditioned media and mRNA for activin beta(A) in explants and HUVECs. We also measured isoprostane and activin A in serum from 21 women with preeclampsia and from 20 women with a normal pregnancy. Treatment with X/XO significantly increased 8-isoprostane production from placental explants, HUVECs and monocytes, indicative of oxidative stress, and significantly increased activin A output from placental explants (139.1 +/- 27.4 per mg wet weight vs 322.9 +/- 89.7 pg/ml per mg wet weight, P = 0.02) and from HUVECs (1.2 +/- 0.2 vs 3.2 +/- 1.8 ng/ml, P = 0.04). There was no effect on activin A output from monocytes. X/XO significantly increased beta(A) mRNA in placental explants but not in HUVECs. Maternal plasma levels of 8-isoprostane and activin A were significantly higher in women with preeclampsia when compared with controls (333.8 +/- 70 vs 176.3 +/- 26.2 pg/ml, P = 0.04 and 49.5 +/- 7 vs 13.1 +/- 1.2 ng/ml, P < 0.001 respectively). In the women with preeclampsia, but not in those with a normal pregnancy, circulating levels of 8-isoprostane and activin A were significantly and positively correlated (r(2) = 0.72; P < 0.001). These data suggest that oxidative stress may be one of the mechanisms underlying increased circulating activin A in preeclampsia. PMID- 17332519 TI - Impact of maternal undernutrition on the hypothalamic-pituitary-adrenal axis responsiveness in sheep at different ages postnatal. AB - Epidemiological and experimental data support the hypothesis of 'fetal programming', which proposes that alterations in fetal nutrition and endocrine status lead to permanent adaptations in fetal homeostatic mechanisms, producing long-term changes in physiology and determine susceptibility to later disease. Altered hypothalamic-pituitary-adrenal (HPA) axis function has been proposed to play an important role in programming of disease risk. The aim of the present study was to examine the effects of maternal nutrient restriction imposed during different periods of gestation on the HPA axis function in sheep, at different ages postnatal. Pregnant ewes were fed a 50% nutrient-restricted diet from days 0 30 (group R1, n = 7), or from days 31-100 of gestation (group R2, n = 7) or a control 100% diet throughout pregnancy, (Control, n = 8). Blood samples were collected at 10-day intervals from day 40 of gestation to term. Lambs were born naturally and fed to appetite throughout the study period. At 2, 5.5, and 10 months of age lambs were given an i.v. injection of corticotrophin-releasing hormone (CRH) and blood samples were collected at -15, 0, 15, 30, 60, 120, and 180 min postinjection. Maternal cortisol levels were significantly higher (P < 0.05) in group R1 compared with the other two groups, whereas maternal insulin levels were lower (P < 0.05) in group R2 compared with control. Birth weight of lambs was not affected by the maternal nutritional manipulation. The area under the curve for ACTH and cortisol response to CRH challenge was greater (P < 0.05) in lambs of group R1 at two months of age, whereas no difference was detected at the ages of 5.5 and 10 months. However, significantly higher (P < 0.01) basal cortisol levels were observed in lambs of R1 group at 5.5 months of age. There was no interaction between treatment and sex for both pituitary and adrenal responses to the challenge. A significant sex effect was evident with females responding with higher ACTH and cortisol levels at the age of 5.5 months (P < 0.01, P < 0.001 respectively) and with higher cortisol levels (P < 0.01) at 10 months of age than males. It is concluded that the HPA axis is programmable by altered nutrition in utero. The sensitivity of the axis to exogenous stimulation is enhanced during early postnatal life and attenuated with age, suggesting a role for the postnatal influences in resetting of the HPA axis and emphasizing the importance of identifying the impact of maternal undernutrition at several time points after birth. PMID- 17332520 TI - Pregnancy associated plasma protein-A is necessary for expeditious fracture healing in mice. AB - Pregnancy-associated plasma protein A (PAPP-A), a metalloproteinase that regulates IGF bioavailability in vitro through cleavage of inhibitory IGF-binding protein-4 (IGFBP-4), has been implicated in skeletal development and injury repair responses. However, direct in vivo data are lacking. In this study, we used PAPP-A knock-out (KO) mice to determine the role of PAPP-A in fracture repair. Stabilized mid-shaft fractures were produced in femurs of 3-month-old mice. At 14 days post-fracture, complete bony bridging of the fracture callus was seen radiographically in wild-type but not in PAPP-A KO mice. Histological examination 5 to 28 days post-fracture showed reductions in the amount of intramembranous bone formation, cartilage production, endochondral ossification and remodeling in PAPP-A KO compared with wild-type mice. However, fracture healing appeared similar in both groups at 42 days post-fracture when analyzed by histology. A similar degree of healing strength in wild-type and PAPP-A KO femurs was demonstrated by mechanical testing at 28 and 42 days post-fracture. Untreated cultures of day 5 fracture calluses from wild-type mice showed robust IGFBP-4 protease activity and IGF receptor phosphorylation, whereas fracture calluses from PAPP-A KO mice had no IGFBP-4 protease activity and reduced IGF receptor phosphorylation. These data demonstrate a marked delay in fracture healing in PAPP-A KO compared with wild-type mice, and suggest that PAPP-A is necessary in the early phases of the process for expeditious fracture repair. The ability of PAPP-A to enhance local IGF action may be an important mechanism for optimizing the fracture repair response. PMID- 17332521 TI - Strain-specific steroidal control of pituitary function. AB - We have previously shown that 7B2 null mice on the 129/SvEvTac (129) genetic background die at 5 weeks of age with hypercorticosteronemia due to a Cushing's like disease unless they are rescued by adrenalectomy; however, 7B2 nulls on the C57BL/6NTac (B6) background remain healthy, with normal steroid levels. Since background exerts such a profound influence on the phenotype of this mutation, we have evaluated whether these two different mouse strains respond differently to high circulating steroids by chronically treating wild-type 129 and B6 mice with the synthetic steroid dexamethasone (Dex). Dex treatment decreased the dopamine content of the neurointermediate lobes (NIL) of 129 mice, leading to NIL enlargement and increased total D(2)R mRNA in the 129, but not the B6, NIL. Despite the decrease in this inhibitory transmitter, Dex-treated 129 mice exhibited reduced circulating alpha-melanocyte-stimulating hormone (alpha-MSH) along with reduced POMC-derived peptides compared with controls, possibly due to reduced POMC content in the NIL. In contrast, Dex-treated B6 mice showed lowered cellular ACTH, unchanged alpha-MSH and beta-endorphin, and increased circulating alpha-MSH, most likely due to increased cleavage of NIL ACTH by increased PC2. Dex-treated 129 mice exhibited hyperinsulinemia and lowered blood glucose, whereas Dex-treated B6 mice showed slightly increased glucose levels despite their considerably increased insulin levels. Taken together, our results suggest that the endocrinological response of 129 mice to chronic Dex treatment is very different from that of B6 mice. These strain-dependent differences in steroid sensitivity must be taken into account when comparing different lines of transgenic or knockout mice. PMID- 17332522 TI - Effects of genistein, resveratrol, and quercetin on steroidogenesis and proliferation of MA-10 mouse Leydig tumor cells. AB - This study was performed to compare the effects of three well-known phytoestrogens such as genistein, resveratrol, and quercetin on steroidogenesis in MA-10 mouse tumor Leydig cells. Addition of genistein or resveratrol to MA-10 cells resulted in decreases in the cAMP-stimulated progesterone secretion, but quercetin had an opposite response. Steroidogenic acute regulatory (StAR) mRNA expression and StAR promoter activity in transiently transfected MA-10 cells were significantly reduced by genistein or resveratrol, but increased by quercetin. Genistein was found to inhibit MA-10 cell proliferation, while resveratrol and quercetin had no effect. Quercetin-induced increase in cAMP-stimulated progesterone secretion was reversed by ICI 182,780, an estrogen receptor (ER) antagonist. However, ICI 182,780 had no effect on cAMP plus quercetin-stimulated StAR promoter activity. To examine whether non-ER factors are associated with quercetin-stimulated progesterone production, we treated MA-10 cells with EGTA to deprive them of extracellular Ca(2+). We found that EGTA inhibited quercetin-plus cAMP-stimulated progesterone secretion and StAR promoter activity. Blocking of Ca(2+) influx through L- or T-type voltage-gated Ca(2+) channels with verapamil or mibefradil respectively, attenuated quercetin-stimulated progesterone secretion, while they had no effect on quercetin-plus cAMP-stimulated StAR promoter activity. Blocking of intracellular Ca(2+) efflux by sodium orthovanadate, a Ca(2+)-pump inhibitor, blocked quercetin- plus cAMP-stimulated progesterone secretion and StAR promoter activity in MA-10 cells. Finally, EGTA or vanadate reduced quercetin and cAMP-increased in StAR mRNA expression in MA-10 cells, while ICI 182,780 had no effect. Taken together, these results indicate that phytoestrogens have differential effects on steroidogenesis in MA-10 cells. PMID- 17332523 TI - Utilization of DR1 as true RARE in regulating the Ssm, a novel retinoic acid target gene in the mouse testis. AB - Various nuclear receptors form dimers to activate target genes via specific response elements located within promoters or enhancers. Retinoid X receptor (RXR) serves as a dimerization partner for many nuclear receptors including retinoic acid receptor (RAR) and peroxisome proliferator-activated receptor (PPAR). Dimers show differential preference towards directly repeated response elements with 1-5 nucleotide spacing, and direct repeat 1 (DR1) is a promiscuous element which recruits RAR/RXR, RXR/RXR, and PPAR/RXR in vitro. In the present investigation, we report identification of a novel RAR/RXR target gene which is regulated by DR1s in the promoter region. This gene, namely spermatocyte-specific marker (Ssm), recruits all the three combinations of nuclear receptors in vitro, but in vivo regulation is observed by trans-retinoic acid-activated RAR/RXR dimer. Indeed, chromatin immunoprecipitation experiment demonstrates binding of RARbeta and RXRalpha in the promoter region of the Ssm. Interestingly, expression of Ssm is almost exclusively observed in spermatocytes in the adult mouse testis, where RA signaling is known to regulate developmental program of male germ cells. The results show that Ssm is a RAR/RXR target gene uniquely using DR1 and exhibits stage-specific expression in the mouse testis with potential function in later stages of spermatogenesis. This finding exemplifies usage of DR1s as retinoic acid response element (RARE) under a specific in vivo context. PMID- 17332524 TI - The effect of testosterone, dihydrotestosterone and oestradiol on the re initiation of spermatogenesis in the adult photoinhibited Djungarian hamster. AB - The roles of testosterone (T) and its metabolites on hamster spermatogenesis are poorly defined. This study assessed the effects of T, dihydrotestosterone (DHT) and oestradiol (E) on the re-initiation of spermatogenesis in the adult Djungarian hamster. Hamsters raised under long photoperiods (LD, 16 h light:8 h darkness) were exposed to short photoperiods (SD, 8 h light:16 h darkness) for 11 weeks to suppress gonadotrophins. Groups of eight animals then received T, DHT and E for 5 weeks. Cell numbers were determined using the optical disector (sic). The number of Sertoli cells was suppressed in SD controls to 48% (P < 0.001) of LD control and restored either fully or partially by exogenous DHTand E (2.6- and 1.8-fold above SD levels) respectively, corresponding with a twofold elevation of serum FSH. The number of germ cells in SD animals was reduced (all P < 0.001) to levels reported. The number of type A spermatogonia increased in line with the rise in Sertoli cell number, by 2.6-fold (P < 0.01) and 1.8-fold (NS) above SD controls after DHT and E treatments respectively. DHT increased the number of type B spermatogonia/preleptotene spermatocytes, leptotene/zygotene and pachytene spermatocytes by 3.5-, 5.7- and 21-fold above SD (all P < 0.01) respectively, compared with a 2.2-fold (P < 0.01), 2.4-fold (not significant, NS) and 6-fold (NS) in E-treated animals respectively. Exogenous T had little effect on cell numbers or serum FSH compared with SD controls. Spermatids were rarely observed after steroid treatment. We believe this study suggests that steroids can regulate the re-initiation of early spermatogenic cells via a mechanism which includes FSH. PMID- 17332526 TI - Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. AB - Adipose tissue plays a central role in determining whole body insulin sensitivity. Several aspects of adipose cell function are regulated by androgens. Given that high androgen levels and insulin resistance are linked in women, we proposed that androgens may influence insulin-mediated glucose metabolism in adipose cells. Preadipocytes harvested from s.c. adipose tissue of healthy women aged 37 +/- 5 years were differentiated in vitro, then treated with testosterone (T) and/or androgen receptor (AR) antagonists (cyproterone acetate, flutamide) for 48 h. Maximal insulin-stimulated glucose uptake (insulin 10 nM) and increment following insulin stimulation were significantly impaired in cells treated with T 10 and 100 nmol/l. This defect was abolished by cyproterone acetate and partially reversed by flutamide. The effect of T could not be accounted for by altered differentiation status of the adipocytes. In the glucose metabolic pathway of insulin signaling, treatment of cells with T 10 nmol/l did not alter insulin stimulated phosphorylation of insulin receptor substrate-1 or Akt, but insulin stimulated phosphorylation of protein kinase C (PKC) zeta was impaired. Insulin signaling via the mitogenic/gene regulatory pathway, as assessed by extracellular signal-regulated kinase phosphorylation, was unchanged. We conclude that (1) T, or an androgenic metabolite of T, induces insulin resistance in adipocytes of women, selective for metabolic signaling pathways; (2) this defect is via AR; and (3) the defect in signaling is independent of phosphatidylinositol 3-kinase activation and involves impaired phosphorylation of PKCzeta. These findings are relevant to understanding the pathogenesis of insulin resistance in hyperandrogenic women. PMID- 17332525 TI - Unraveling the molecular targets pertinent to junction restructuring events during spermatogenesis using the Adjudin-induced germ cell depletion model. AB - During spermatogenesis, extensive restructuring takes place at the Sertoli Sertoli and Sertoli-germ cell interface, which is regulated via intriguing interactions among cytokines, proteases, protease inhibitors, kinases, phosphatases, and transcription factors. This in turn determines the steady-state levels of integral membrane proteins at the cell junctions. We sought to further expand these observations using the Adjudin model. Adjudin is a potential male contraceptive that targets Sertoli-germ cell adhesion, causing exfoliation of spermatids and spermatocytes, but not spermatogonia, from the seminiferous epithelium. This model thus provides the means to identify crucial regulatory molecules and signaling pathways pertinent to junction restructuring events during spermatogenesis. In this study, genome-wide expression profiling of rat testes after treatment with Adjudin at the time of extensive junction restructuring was performed. Differentially regulated genes, such as cytokines, proteases, protease inhibitors, cell junction-associated proteins, and transcription factors pertinent to junction restructuring were identified. These data were consistent with earlier findings; however, much new information was obtained which has been deposited at the Gene Expression Omnibus data repository website: http://www.ncbi.nih.gov/geo/ with Accession number: GSE5131. The primary signaling events pertinent to junction restructuring in the testis induced by Adjudin were also delineated using bioinformatics. These findings were also consistent with recently published reports. The identified molecular signatures or targets pertinent to junction dynamics in the testis as reported herein, many of which have not been investigated, thus offer a framework upon which the regulation of junction restructuring events at the Sertoli-Sertoli and Sertoli germ cell interface pertinent to spermatogenesis can be further studied. PMID- 17332527 TI - A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats. AB - Fasudil, a Rho-kinase inhibitor, may improve insulin signaling. However, its long term effect on metabolic abnormalities and its preventive effect on diabetic nephropathy are still unknown. We assessed these effects of fasudil in insulin resistant diabetic rats, comparing them with those of an angiotensin II receptor blocker, olmesartan. Male Otsuka Long-Evans Tokushima fatty (OLETF) and Long Evans Tokushima Otsuka, non-diabetic control, rats at 15 weeks of age were used. OLETF rats were randomized to receive a low or a high dose of fasudil or olmesartan for 25 weeks. To examine the therapeutic effects after the development of diabetes, OLETF rats at 30 weeks of age were given fasudil for 10 weeks. Administration of high-dose fasudil completely suppressed the development of diabetes, obesity, and dyslipidemia and increased serum adiponectin levels in OLETF rats. High-dose olmesartan also decreased hemoglobin A1c and increased serum adiponectin. There was a significant correlation between hemoglobin A1c and serum adiponectin or free fatty acid levels. The treatment with high-dose fasudil ameliorated proteinuria, glomerulosclerosis, renal interstitial fibrosis, and macrophage infiltration in OLETF rats. Olmesartan, even at the low dose, suppressed renal complications. The treatment with fasudil after the development of diabetes improved the metabolic abnormalities in OLETF rats, but could not suppress the progression of nephropathy. We conclude that the long-term treatment with fasudil prevents the development of diabetes, at least in part, by improving adipocyte differentiation in insulin-resistant diabetic rats. Early use of fasudil may prevent diabetic nephropathy. PMID- 17332528 TI - Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin. AB - The mammalian hypothalamus comprises an array of phenotypically distinct cell types that interpret peripheral signals of energy status and, in turn, elicits an appropriate response to maintain energy homeostasis. We used a clonal representative hypothalamic cell model expressing proopiomelanocortin (POMC; N 43/5) to study changes in AMP-activated protein kinase (AMPK) activity and glucose responsiveness. We have demonstrated the presence of cellular machinery responsible for glucose sensing in the cell line, including glucokinase, glucose transporters, and appropriate ion channels. ATP-sensitive potassium channels were functional and responded to glucose. The N-43/5 POMC neurons may therefore be an appropriate cell model to study glucose-sensing mechanisms in the hypothalamus. In N-43/5 POMC neurons, increasing glucose concentrations decreased phospho-AMPK activity. As a relevant downstream effect, we found that POMC transcription increased with 2.8 and 16.7 mM glucose. Upon addition of leptin, with either no glucose or with 5 mM glucose, we found that leptin decreased AMPK activity in N 43/5 POMC neurons, but had no significant effect at 25 mM glucose, whereas insulin decreased AMPK activity at only 5 mM glucose. These results demonstrate that individual hypothalamic neuronal cell types, such as the POMC neuron, can have distinct responses to peripheral signals that relay energy status to the brain, and will therefore be activated uniquely to control neuroendocrine function. PMID- 17332529 TI - Duox expression and related H2O2 measurement in mouse thyroid: onset in embryonic development and regulation by TSH in adult. AB - In the thyroid, H(2)O(2) is produced at the apical pole of thyrocytes by one or two NADPH oxidases (NOX), Duox1/2 proteins. The onset of Duox expression was analysed by immunohistochemistry in the developing mouse thyroid in parallel with thyroglobulin (Tg) iodination and the expression of other thyroid differentiation markers. Duox proteins were found at embryonic day (E) 15.5 and were mainly localised at the apical pole of thyrocytes. Tg was detected 1 day before (E14.5) and Tg iodination was concomitant with the expression of both Duox and Na(+)/I(-) symporter (NIS; E15.5). The role of TSH in regulating Duox expression and H(2)O(2) accumulation was evaluated in thyroids of adult mice with reduced (Tshr(hyt/hyt) or mice treated with thyroxine) or increased (methimazole or perchlorate treatment) TSH/Tshr activity. In mice with suppressed TSH/Tshr activity, Duox expression was only partially decreased when compared with wild type, as observed by western blot. In Tshr(hyt/hyt) strain, Duox was still expressed at the apical pole and H(2)O(2) measurements were normal. On the other hand, chronic TSH stimulation of the gland led to a decrease of H(2)O(2) measurements without affecting Duox expression. The onset of Duox protein expression is compatible with their proposed function in thyroid hormone synthesis and it can be considered as a functional marker of the developing thyroid. However, Duox expression in adult is much less regulated by TSH than NIS and thyroperoxidase. It is not always correlated with the overall thyroid H(2)O(2) accumulation, highlighting the importance of additional regulatory mechanisms which control either the production or H(2)O(2) degradation. PMID- 17332530 TI - Endogenous thyrocyte-produced nitric oxide inhibits iodide uptake and thyroid specific gene expression in FRTL-5 thyroid cells. AB - Nitric oxide (NO) is a free radical that mediates a wide array of cell functions. It is generated from l-arginine by NO-synthase (NOS). Expression of NOS isoforms has been demonstrated in thyroid cells. Previous reports indicated that NO donors induce dedifferentiation in thyrocytes. However, the functional significance of endogenous thyrocyte-produced NO has not been explored. This work aimed to study the influence of endogenous NO on parameters of thyroid cell function and differentiation in FRTL-5 cells. We observed that treatment with the NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), increased the TSH stimulated iodide uptake. The TSH-induced sodium iodide symporter (NIS) and thyroglobulin (TG) mRNA expressions were increased after incubation with L-NAME. In transient transfection assays, TSH-stimulated transcriptional activities of NIS and TG promoters were increased by L-NAME. An increment of the TSH-stimulated cell proliferation was observed after NOS inhibition. Similar results were obtained when the action of another NOS inhibitor, N(g)-monomethyl-L-arginine, was analysed for most of these studies. The production of NO, which was not detectable in basal conditions, was increased by TSH. Our data provide strong evidence that endogenous NO could act as a negative signal for TSH-stimulated iodide uptake and thyroid-specific gene expression as well as proliferation in thyrocytes. These findings reveal a possible new inhibitory pathway in the regulation of thyroid cell function. PMID- 17332531 TI - Growth hormone stimulates osteoprotegerin expression and secretion in human osteoblast-like cells. AB - It is presently thought that osteoprotegerin (OPG) is a cytokine involved in the regulation of osteoblast/osteoclast crosstalk and maintenance of bone mass. Recent studies showed that GH replacement therapy in GH-deficient patients was able to induce a significant increase of OPG in the plasma, as well as in the cortical and the trabecular bone. In order to determine whether GH could directly modulate OPG secretion, the effect of GH on human osteoblast-like cells (hOB) in primary culture was studied. After detecting the presence of the mRNA for the GH receptor (GHR) by RT-PCR, hOB were exposed to increasing concentrations of GH, from 0.1 to 25 ng/ml, for 24 h. The results showed that GH exposure was able to stimulate OPG secretion in a concentration-dependent manner. In addition, the OPG mRNA levels were increased, indicating that the hormone has a stimulatory effect on gene expression. The stimulatory effect on OPG expression and production was prevented by exposing the cells to tyrphostin AG490 (10 muM), an inhibitor of Janus kinase 2, which is one of the kinases involved in the intracellular pathway activated by the binding of GH to its receptor. Similar results were obtained when the cells were exposed to a receptor antagonist of GH, pegvisomant at 50 nM. GH exposure neither induced an increase in IGF-I expression nor secretion in hOB. These results suggest that the stimulation of OPG production induced by GH in hOB is specific and receptor mediated and further support the view that GH is able to modulate bone remodeling by directly influencing osteoblast-osteoclast crosstalk. PMID- 17332532 TI - Increased extracellular signal regulated kinases phosphorylation in the adrenal gland in response to chronic ACTH treatment. AB - ACTH released from the pituitary acts through activation of cAMP/PKA in adrenocortical cells stimulating steroidogenesis. Although ACTH was originally thought to have anti-proliferative effects on the adrenal, recently it has been described that it could also have proliferative effects acting through other signalling cascades. This is also relevant in humans given the increased levels of ACTH occurring together with adrenal cortex hyperplasia observed in Cushing's disease and possibly in other situations such as chronic stress. One of the signalling pathways regulating cell proliferation is the extracellular signal regulated kinase (ERKs) pathway. ERKs are members of the MAPK family of cascades. They are activated by extracellular stimuli such as growth factors and mitogens, become phosphorylated through MEK1/2 and regulate a diversity of cellular processes such as proliferation and differentiation. Until now, no study addressed the effects of chronic ACTH administration on the activation of ERKs in vivo. Using rats submitted to different ACTH dosages as well as variable durations, we determined if ACTH induced ERKs activation and by establishing a parallelism with proliferating cell nuclear antigen (PCNA) expression, we aimed to demonstrate a role of ACTH-induced ERKs activation in cell proliferation. Blood was collected for hormonal analysis and the role of ACTH-induced ERKs activation in the stimulation of steroidogenesis was also studied. We confirmed that ACTH increased adrenal weight and corticosterone levels when compared with control or dexamethasone-treated animals. We also demonstrated that ACTH increases ERKs activation and PCNA expression in a time- and dose-dependent manner. When ERKs activation was blocked by the use of a specific MEK inhibitor (PD98059), there was a decrease in ACTH-induced corticosterone release and PCNA expression. We conclude that chronic ACTH induces ERKs activation and that this plays an important role in the induction of cell proliferation as well as steroidogenesis. PMID- 17332533 TI - Protein kinase C phosphorylates the inositol 1,4,5-trisphosphate receptor type 2 and decreases the mobilization of Ca2+in pancreatoma AR4-2J cells. AB - In non-excitable cells, the inositol 1,4,5-trisphosphate receptor channel, which plays a major (IP(3)R) is an intracellular Ca(2+) role in Ca(2+) signalling. Three isoforms of IP(3)R have been identified (IP(3)R-1, IP(3)R-2 and IP(3)R-3) and most cell types express different proportions of each isoform. The differences between the pharmacological and functional properties of the various isoforms of IP(3)R are poorly understood. AR4-2J cells, which express almost exclusively (~86%) the IP(3)R-2, represent an interesting model to study this particular isoform. Here, we investigated a regulatory mechanism by which protein kinase C (PKC) influences IP(3)R-2-mediated Ca(2+) release. Using an immunoprecipitation approach, we confirmed that AR4-2J cells express almost exclusively the IP(3)R-2 isoform. Using an in vitro phosphorylation assay, we showed that the immunopurified IP(3)R-2 was efficiently phosphorylated by exogenous PKC. In intact AR4-2J cells metabolically labelled with (32)Pi, we showed that phorbol-12-myristate-13-acetate (PMA) and Ca(2+) mobilizing agonists cause the phosphorylation of IP(3)R-2. In saponin-permeabilized AR4-2J cells, IP(3)-induced Ca(2+) release was reduced after a pre-treatment with PMA or with exogenous PKC. PMA also reduced the Ca(2+) response of intact AR4-2J cells stimulated with carbachol and epidermal growth factor, two agonists that use different receptor types to activate phospholipase C. These results demonstrate that PKC decreases the Ca(2+)mobilizing activity of IP(3)R-2 and thus exerts a negative feedback on the agonists-induced Ca(2+) response of AR4-2J cells. PMID- 17332534 TI - Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level. AB - To test putative interdependence in the ontogenesis of the hypothalamic-pituitary gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCRalphabeta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCRalphabeta(-), TCRalphabeta(low) and TCRalphabeta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCRalphabeta(low) developmental stage accompanied by an increased positive/ reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCRalphabeta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4( )CD8(+) cells without changes in that of CD4(+)8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCRalphabeta(high) thymocytes towards CD4(-)8(+) TCRalphabeta(high) cells followed by increased emigration of the mature cells and (ii) decelerated differentiation and maturation towards CD4(+)8(-)TCRalphabeta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction. PMID- 17332535 TI - Drosophila follicle cells are patterned by multiple levels of Notch signaling and antagonism between the Notch and JAK/STAT pathways. AB - The specification of polar, main-body and stalk follicle cells in the germarium of the Drosophila ovary plays a key role in the formation of the egg chamber and polarisation of its anterior-posterior axis. High levels of Notch pathway activation, resulting from a germline Delta ligand signal, induce polar cells. Here we show that low Notch activation levels, originating from Delta expressed in the polar follicle cells, are required for stalk formation. The metalloprotease Kuzbanian-like, which cleaves and inactivates Delta, reduces the level of Delta signaling between follicle cells, thereby limiting the size of the stalk. We find that Notch activation is required in a continuous fashion to maintain the polar and stalk cell fates. We further demonstrate that mutual antagonism between the Notch and JAK/STAT signaling pathways provides a crucial facet of follicle cell patterning. Notch signaling in polar and main-body follicle cells inhibits JAK/STAT signaling by preventing STAT nuclear translocation, thereby restricting the influence of this pathway to stalk cells. Conversely, signaling by JAK/STAT reduces Notch signaling in the stalk. Thus, variations in the levels of Notch pathway activation, coupled with a continuous balance between the Notch and JAK/STAT pathways, specify the identity of the different follicle cell types and help establish the polarity of the egg chamber. PMID- 17332536 TI - ERK- and JNK-signalling regulate gene networks that stimulate metamorphosis and apoptosis in tail tissues of ascidian tadpoles. AB - In ascidian tadpoles, metamorphosis is triggered by a polarized wave of apoptosis, via mechanisms that are largely unknown. We demonstrate that the MAP kinases ERK and JNK are both required for the wave of apoptosis and metamorphosis. By employing a gene-profiling-based approach, we identified the network of genes controlled by either ERK or JNK activity that stimulate the onset of apoptosis. This approach identified a gene network involved in hormonal signalling, in innate immunity, in cell-cell communication and in the extracellular matrix. Through gene silencing, we show that Ci-sushi, a cell-cell communication protein controlled by JNK activity, is required for the wave of apoptosis that precedes tail regression. These observations lead us to propose a model of metamorphosis whereby JNK activity in the CNS induces apoptosis in several adjacent tissues that compose the tail by inducing the expression of genes such as Ci-sushi. PMID- 17332537 TI - Folic acid and birth malformations. PMID- 17332538 TI - Housing and health. PMID- 17332539 TI - The pharmaceutical price regulation scheme. PMID- 17332540 TI - Regulation of doctors. PMID- 17332541 TI - Management of breast cancer in women with BRCA gene mutation. PMID- 17332542 TI - Look at all the evidence before stockpiling amantadine. PMID- 17332543 TI - It's only numbers. PMID- 17332544 TI - HIV funding: debate misses the point. PMID- 17332545 TI - Double effect is a myth leading a double life. PMID- 17332546 TI - Beware the "Texas sharp shooter" in rate ratios of progression. PMID- 17332547 TI - The urge to sprinkle statistics is irresistible. PMID- 17332548 TI - World Health Organization refutes allegations. PMID- 17332549 TI - Doctors lose power to regulate their profession. PMID- 17332551 TI - Europe needs two or three years to prepare for pandemic flu. PMID- 17332552 TI - UK nears European average in proportion of GDP spent on health care. PMID- 17332553 TI - New once a day, fixed dose antimalarial is now available for adults and children. PMID- 17332555 TI - Misuse of prescription drugs could soon exceed that of illicit narcotics, UN panel warns. PMID- 17332556 TI - US health policy experts call for a centre to compare treatments. PMID- 17332557 TI - Guidance recommends asking pregnant women about mental health. PMID- 17332558 TI - HFEA allows women to donate eggs for research. PMID- 17332561 TI - Internet doctor is suspended for irresponsible prescribing. PMID- 17332562 TI - NICE says doctors should identify people at high risk of contracting sexually transmitted infections. PMID- 17332563 TI - Experts call for close scrutiny of new cancer centres. PMID- 17332565 TI - Number of people in UK with dementia will more than double by 2050. PMID- 17332567 TI - New guidelines on preventing heart disease in women propose aspirin for all aged over 65. PMID- 17332569 TI - Repeal law that puts "FDA on the payroll of the industry," says former NEJM editor. PMID- 17332570 TI - Simple precautionary measures can reduce numbers of falls in hospital. PMID- 17332578 TI - Will we be getting good doctors and safer patients? PMID- 17332579 TI - Will we be getting good doctors and safer patients? PMID- 17332580 TI - Will we be getting good doctors and safer patients? PMID- 17332581 TI - Will we be getting good doctors and safer patients? PMID- 17332582 TI - Will we be getting good doctors and safer patients? PMID- 17332583 TI - Fitting the drug to the patient. PMID- 17332584 TI - Killing me softly. PMID- 17332585 TI - Designing and evaluating complex interventions to improve health care. PMID- 17332586 TI - Management of kidney stones. PMID- 17332587 TI - Hyponatraemia and hypernatraemia: pitfalls in testing. PMID- 17332593 TI - Invited commentary. PMID- 17332599 TI - Ontogenic development-associated changes in the expression of genes involved in rat bile acid homeostasis. AB - Ontogenic changes in the rat bile acid (BA) pool, measured enzymatically and by GC-MS, and expression of enzymes (5alpha-reductase, 5beta-reductase, and cytochrome P450 enzymes Cyp7a1, Cyp8b1, Cyp27 and Cyp3a11), transporters [bile salt export pump, sodium taurocholate-cotransporting polypeptide, apical sodium dependent bile acid transporter, and organic solute transporter alpha/beta (Ostalpha/Ostbeta)], and nuclear receptors [fetoprotein transcription factor (Ftf), farnesoid X receptor (Fxr), small heterodimer partner (Shp), and hepatic nuclear factor 4alpha (HNF-4alpha)], determined by quantitative PCR, were investigated. The absolute size of the BA pool increased progressively up to adulthood, whereas the complexity of its composition was high in fetuses, decreased after birth, increased again progressively up to adulthood, and decreased in aged animals. Allo-cholic acid only appeared early in development, in spite of low 5alpha-reductase expression. The relative size of the BA pool, corrected by liver weight, was maintained from 1 week after birth, except at weaning, when a transient peak accompanied by Shp downregulation and Cyp7a1 upregulation was observed. An imposed weaning delay of 1 week had no effect on the time course of the BA pool size but decreased the proportion of chenodeoxycholic and alpha-muricholic acids, whereas the proportion of cholic acid was increased, probably as a result of Cyp8b1 upregulation. In conclusion, changes in the expression of genes involved in BA homeostasis may play a role in physiological adaptations to digestive functions during the rat life span. PMID- 17332600 TI - The nuclear medicine practitioner: SNMTS task force identifies need for new role. PMID- 17332604 TI - Taking care of business. PMID- 17332605 TI - CARE bill reintroduced in house. PMID- 17332606 TI - PET: speed dating CT or MRI? PMID- 17332607 TI - In vivo leukocyte labeling: the quest continues. PMID- 17332608 TI - Being right for the right reason: better than just being right? PMID- 17332609 TI - 99mTc-labeled interleukin 8 for the scintigraphic detection of infection and inflammation: first clinical evaluation. AB - Interleukin 8 (IL-8) is a chemotactic cytokine that binds with a high affinity to receptors expressed on neutrophils. Previous studies with various animal models showed that (99m)Tc-labeled IL-8 accumulates specifically and rapidly in infectious and inflammatory foci. The aims of the present study were to evaluate the safety of IL-8 in humans and to assess the value of (99m)Tc-IL-8 scintigraphy in patients with suspected localized infections. METHODS: (99m)Tc-IL-8 was intravenously injected at 400 MBq into 20 patients with various suspected localized infections. Patients were monitored for IL-8-related side effects for 4 h. Whole-body imaging was performed directly after injection and at 4 h after injection. Imaging after 24 h was performed for the first 7 patients and for subsequent patients when the results of (99m)Tc-IL-8 scintigraphy at 4 h after injection were normal or equivocal. Blood was drawn at several time points to determine the total number of leukocytes and leukocyte differentiation (all patients) and to determine pharmacokinetics (6 patients). RESULTS: (99m)Tc-IL-8 scintigraphy was performed for 20 patients (13 men and 7 women) with a mean age of 60 y (range, 21-76 y). No significant side effects were noted. Patients had suspected joint prosthesis infections (n = 9), osteomyelitis (n = 8), liver abscess (n = 1), and soft-tissue infections (n = 2). (99m)Tc-IL-8 was rapidly cleared from the blood and most other organs. In 10 of 12 patients with infections, (99m)Tc-IL-8 localized the infection at 4 h after injection. In 1 patient with vertebral osteomyelitis and in 1 patient with an infected knee prosthesis, (99m)Tc-IL-8 scintigraphy results were false-negative. In 8 patients with noninfectious disorders, no focal accumulation of (99m)Tc-IL-8 was found. CONCLUSION: Injection of (99m)Tc-IL-8 is well tolerated. (99m)Tc-IL-8 scintigraphy is a promising new tool for the detection of infections in patients as early as 4 h after injection. PMID- 17332610 TI - Preoperative risk stratification using gated myocardial perfusion studies in patients with cancer. AB - Cancer patients frequently have anemia or an altered coagulation state that may affect their risk stratification for perioperative cardiac events. We performed this study to investigate the incidence of perioperative cardiac events in cancer patients who had abnormal stress myocardial perfusion imaging (MPI) results versus cancer patients with normal MPI results. METHODS: We included 394 consecutive cancer patients with normal (n = 201) or abnormal (n = 193) results on MPI studies performed for preoperative risk stratification. MPI was performed within 6 mo before each patient's scheduled operation. All the patients had surgical procedures requiring general anesthesia, except for 18 who had endoscopic or colonoscopic procedures. We retrospectively reviewed their data for the incidence of major cardiac events intraoperatively and for 1 mo postoperatively. We collected data on their cancer type, risk factors for coronary artery disease, MPI findings, risk of operation, and intraoperative or postoperative major cardiac events, which included death, myocardial infarction (MI), and congestive heart failure (CHF). RESULTS: The patients with abnormal MPI results included 97 with ischemia, 80 with scarring, and 16 with mixed scarring and ischemia. The mean left ventricular ejection fraction and end-diastolic volume were 63.8% +/- 9.8% and 82.0 +/- 53.5 mL in the normal MPI group versus 52.1% +/- 13.1% and 118.1 +/- 53.4 mL in the abnormal-MPI group (P < 0.001). There were 9 major intraoperative or postoperative cardiac events (4.7%) in the patients with abnormal MPI results and none in the patients with normal MPI results (P = 0.001). These major events consisted of 3 deaths, 2 acute MIs, 1 non Q-wave MI, and 3 cases of CHF. Four of these patients had only scarring on their MPI studies, 3 had ischemia, and 2 had scarring and ischemia. CONCLUSION: Normal MPI results have a high negative predictive value for perioperative cardiac events in cancer patients. Abnormal MPI results, whether demonstrating scarring or ischemia, should prompt appropriate perioperative management in patients with cancer to minimize major cardiac events. PMID- 17332611 TI - Value of vasodilator left ventricular ejection fraction reserve in evaluating the magnitude of myocardium at risk and the extent of angiographic coronary artery disease: a 82Rb PET/CT study. AB - Our aim was to determine the value of vasodilator left ventricular ejection fraction (LVEF) reserve (stress ejection fraction - rest ejection fraction) in evaluating the magnitude of myocardium at risk and the anatomic extent of underlying severe coronary artery disease (CAD). METHODS: We studied 510 consecutive patients with suspected CAD undergoing gated rest and vasodilator stress (82)Rb PET/CT. Patients were categorized as having no perfusion abnormalities, mild, moderate, or severe reversible perfusion defects. In a subgroup of 68 patients with coronary angiography, patients were categorized as having 0-vessel, 1-vessel, 2-vessel, or left main/3-vessel disease. RESULTS: Patients without coronary risk factors who comprised our control group as well as patients with coronary risk factors and normal perfusion demonstrated a high LVEF reserve (7% +/- 7% and 5% +/- 6%, respectively). The mean LVEF reserve was negative (-0.2% +/- 8%) in patients with severe reversible defects and in patients with 3-vessel (-6% +/- 8%) and left main (-8% +/- 5%) disease. Among the clinical and scintigraphic variables studied, male sex, rest ejection fraction, and increasing magnitude of myocardium at risk predicted a lower LVEF reserve, whereas LVEF reserve was the only independent predictor of left main/3-vessel disease (P = 0.008). An LVEF reserve of more than +5% had a positive predictive value of only 41% but a negative predictive value of 97% for excluding severe left main/3-vessel CAD. CONCLUSION: During (82)Rb PET/CT, LVEF increases with vasodilator stress in patients without significant stress-induced perfusion defects or severe left main/3-vessel CAD. A high LVEF reserve appears to be an excellent tool to exclude left main/3-vessel CAD noninvasively. PMID- 17332612 TI - Quantification of striatal dopamine transporters with 123I-FP-CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: a double blind, placebo-controlled, crossover study in healthy control subjects. AB - Dopamine transporter (DAT) imaging with (123)I-FP-CIT ((123)I-N-omega fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) SPECT is frequently used to detect loss of nigrostriatal cells in parkinsonism. Recent (123)I-beta-CIT ((123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) studies have shown a significant increase in striatal-to-nonspecific beta-CIT binding ratios after treatment with selective serotonin reuptake inhibitors (SSRIs). Due to similarities between (123)I-beta-CIT and (123)I-FP-CIT (both are derived from cocaine and show relatively high affinity for the DAT and the serotonin transporter [SERT]), we hypothesized that quantification of striatal (123)I-FP CIT binding may be influenced by SSRIs. Moreover, we hypothesized that (123)I-FP CIT in humans binds not only to DATs but also to central and peripheral SERTs. METHODS: To study the influence of the SSRI paroxetine on (123)I-FP-CIT binding to DATs in the striatum, we conducted a double-blind, placebo-controlled, crossover study with paroxetine in 8 healthy young male control subjects. In addition, we studied whether paroxetine was able to block (123)I-FP-CIT binding in SERT-rich brain areas and in lung tissue, as lung tissue contains a considerable amount of SERTs. Participants were pretreated for 2 d with paroxetine (20 mg/d) or placebo at 2 sessions (crossover design), and brain SPECT was performed 1 and 3 h after (123)I-FP-CIT injection, whereas lung uptake was measured 2 h after injection. RESULTS: Compared with placebo pretreatment, we found after paroxetine pretreatment a statistically significant increase (approximately 10%) in specific striatal-to-nonspecific (123)I-FP-CIT binding ratios at 3 h after injection, a time point at which striatal (123)I-FP-CIT binding ratios are stable. In addition, after paroxetine treatment, statistically significantly lower binding ratios were found in SERT-rich brain areas (e.g., at 1 h after injection, midbrain-to-cerebellar ratios were approximately 90% lower) as well as significantly lower uptake in lung tissue was found (approximately 40% lower after paroxetine). CONCLUSION: In this study we show that the quantification of striatal (123)I-FP-CIT binding to DAT is significantly increased by the SSRI paroxetine in humans. To our knowledge, this is the first study which shows that (123)I-FP-CIT binds in vivo in humans not only to DATs but also to central SERTs and SERTs in lung tissue. PMID- 17332613 TI - 18F-fluorodeoxythymidine PET for evaluating the response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcomas. AB - Locally advanced soft-tissue sarcomas of an extremity can be treated either by amputation of the limb or by hyperthermic isolated limb perfusion (HILP) followed by resection of the tumor. In this study, the response to HILP was measured by PET with (18)F-fluorodeoxythymidine ((18)F-FLT). METHODS: Ten patients with primary nonresectable soft-tissue sarcomas of an extremity underwent HILP with tumor necrosis factor-alpha and melphalan. Before and after HILP, all patients underwent PET with (18)F-FLT for response evaluation. RESULTS: Before HILP, all tumors were clearly visible on (18)F-FLT PET; for the maximum standardized uptake value (SUV(max)), the mean was 3.5 (range, 1.0-6.7), and for the mean standardized uptake value (SUV(mean)), the mean was 1.9 (range, 0.7-2.7). After HILP, all but 1 tumor showed necrosis ranging from 10% to 95%. (18)F-FLT PET after HILP revealed significantly decreased uptake of the tracer. The mean SUV(max) decreased to 1.7 (P = 0.008), and the mean SUV(mean) decreased to 0.8 (P = 0.002). One small axillary lymph node metastasis was not visible on (18)F-FLT PET. CONCLUSION: (18)F-FLT PET revealed high uptake in soft-tissue sarcomas. (18)F-FLT uptake was correlated with the mitotic index of the tumors (r = 0.82 and P = 0.004 for SUV(max); r = 0.87 and P = 0.001 for SUV(mean)). After HILP, the uptake of (18)F-FLT decreased significantly (P = 0.008 and P = 0.002 for SUV(max) and SUV(mean), respectively). Tumors with initially high (18)F-FLT uptake showed a better response to HILP (r = 0.64, P < 0.05). Software fusion of PET images with images from conventional imaging modalities revealed the heterogeneity of the tumors before and after HILP. Such data can help a surgeon in planning the resection of a tumor. PMID- 17332614 TI - The Feasibility of 18F-FDG PET scans 1 month after completing radiotherapy of squamous cell carcinoma of the head and neck. AB - Our purpose was to prospectively evaluate the efficacy of PET with (18)F-FDG 1 mo after the completion of radiotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: Ninety-seven patients underwent (18)F-FDG PET scans before and after radiotherapy for nondisseminated SCCHN. The first scans were obtained no more than 4 wk before the start of radiotherapy, and follow-up scans were obtained 1 mo after the completion of radiotherapy. (18)F-FDG PET images were analyzed using standardized uptake values (SUVs). All patients were followed for at least 6 mo or until death. RESULTS: The median SUVs of preradiotherapy primary sites and nodes were 6.5 (range, 2.3-23.0) and 5.6 (range, 1.2-16.8), respectively. The median SUVs of postradiotherapy primary sites and nodes were 1.8 (range, basal status value to 9.7) and 1.8 (range, basal status value to 8.6), respectively. Evaluation of the postradiotherapy status of tumors in these SCCHN patients showed the sensitivity of (18)F-FDG PET to be 88%, the specificity to be 95%, and the overall diagnostic accuracy to be 94.9%. CONCLUSION: Our results indicate that (18)F-FDG PET might be a valuable imaging method for evaluating the response to radiotherapy in patients with SCCHN. One month after the completion of radiotherapy is not too early for follow-up (18)F FDG PET to be performed to evaluate the response to radiotherapy. PMID- 17332615 TI - Treatment of thyrotoxicosis. AB - In this review, the causes of thyrotoxicosis and the treatment of syndromes with increased trapping of iodine are discussed. The benefits and the potential side effects of 3 frequently used therapies--antithyroid medications, thyroidectomy, and (131)I treatment--are presented. The different approaches to application of (131)I treatment are described. Treatment with (131)I has been found to be cost effective, safe, and reliable. PMID- 17332616 TI - Effect of corticosteroids on 18F-FDG uptake in tumor lesions after chemotherapy. AB - To be a reliable predictor of response, (18)F-FDG uptake should reflect changes in the amount of viable tumor cells. However, (18)F-FDG also accumulates in inflammatory cells. Shortly after treatment, the influx of inflammatory cells in the tumor can therefore interfere with early response evaluation. The aim of this study was to investigate whether this inflammation is suppressed by the administration of corticosteroids and, in turn, can improve the correlation of (18)F-FDG uptake with tumor cell kill. METHODS: Severe combined immunodeficiency mice were inoculated subcutaneously with Daudi cells. When the tumor measured 15 mm, mice were divided in 2 groups treated with 1 single dose of cyclophosphamide, 125 mg/kg (group A) or cyclophosphamide followed by hydrocortisone (0.2 mg/d) for 5 d (group B). The change in (18)F-FDG uptake was evaluated with small-animal PET (5 mice/group) on D+6, D+9, D+13, and D+16 (days after treatment). At each time point, 4 mice per group were sacrificed for quantification of the different tumor cell fractions by flow cytometry and histopathology. Changes in (18)F-FDG uptake were correlated with inflammation and viable tumor cells. RESULTS: Cyclophosphamide administration resulted in a steady reduction in viable cell fraction until D+9 (reduction from baseline, -64%). The viable cell fraction increased again on D+13. A transient influx of inflammatory cells was seen from D+6 to D+13 (peak on D+9, 24% of total cell fraction). After hydrocortisone administration, a similar reduction in the viable cell fraction was seen. The inflammatory response was less pronounced but developed with earlier kinetics (peak on D+6 [15% of total cell fraction], almost resolved on D+9) and consisted primarily of granulocytes instead of mononuclear cells in the absence of corticosteroids. In both groups, a significant reduction in (18)F-FDG uptake was seen until D+6. On D+9, a transient increase in (18)F-FDG uptake was seen in group A, whereas a further decrease was observed in group B. CONCLUSION: After corticosteroid administration, the contribution of inflammatory cells to the (18)F-FDG uptake was less important than that in mice treated with chemotherapy alone. The earlier, but weaker, inflammatory response after corticosteroid administration consists primarily of granulocytes instead of mononuclear cells. PMID- 17332617 TI - Enhanced expression of adenovirus-mediated sodium iodide symporter gene in MCF-7 breast cancer cells with retinoic acid treatment. AB - Increased expression of the sodium iodide symporter (NIS) is required for effective radioiodine treatment and reporter gene imaging of breast cancer. We investigated the effect of retinoic acid on adenovirus-mediated expression of the human NIS gene in the MCF-7 breast cancer cell line. METHODS: The MCF-7 cell line was infected with recombinant adenovirus carrying the human NIS gene (Rad-NIS). Levels of NIS messenger RNA (mRNA) and protein expression and radioiodine ((125)I) uptake were measured to evaluate adenovirus-mediated NIS gene expression in wild-type and Rad-NIS-infected MCF-7 cells after treatment with all-trans retinoic acid (ATRA; 10(-8)-10(-6) mol/L). RESULTS: The transduction efficiency of adenovirus in MCF-7 cells at a multiplicity of infection (MOI) of 50 was >60%. After incubation with 10(-6) mol/L ATRA, the mRNA level in Rad-NIS-infected MCF-7 cells increased to 118.5 times that of wild-type MCF-7 cells, whereas the mRNA level in wild-type MCF-7 cells showed only a 2.1-fold increase. Western blot, immunocytochemical staining, and flow cytometry analyses showed that NIS protein expression in MCF-7 cells infected with Rad-NIS increased after ATRA treatment. With ATRA treatment, the amount of (125)I uptake increased in a dose-dependent manner (P < 0.001). The (125)I uptake in wild-type MCF-7 cells increased 3.1-, 5.5-, and 7.6-fold with treatment with 10(-8), 10(-7), and 10(-6) mol/L ATRA, respectively. Rad-NIS-infected cells showed a 4.0-fold increase in (125)I uptake. Treatment of Rad-NIS-infected cells with 10(-8), 10(-7), and 10(-6) mol/L ATRA increased (125)I uptake by 4.9-, 8.2-, and 27.6-fold, respectively, compared with wild-type MCF-7 cells. The level of NIS expression in Rad-NIS-infected MCF-7 cells treated with 10(-6) mol/L ATRA (245.0 +/- 13.7 pmol/10(6) cells) was much greater than the sum of the expression levels seen in ATRA-treated wild-type cells and Rad-NIS-infected wild-type cells. CONCLUSION: Retinoic acid increases adenovirus-mediated NIS expression in MCF-7 cells. Our results indicate that improved efficiency of NIS gene therapy or reporter imaging in breast cancer may be possible with retinoic acid treatment. PMID- 17332618 TI - Intramyocardial Implantation of bone marrow-derived stem cells enhances perfusion in chronic myocardial infarction: dependency on initial perfusion depth and follow-up assessed by gated pinhole SPECT. AB - Cell therapy-induced changes in the perfusion of areas of myocardial infarction (MI) remain unclear. This study investigated whether an original pinhole SPECT technique could be applied to a rat MI model to analyze local improvement in myocardial perfusion relating to engraftment sites of bone marrow-derived stem cells (BMSCs). METHODS: Four-month-old MI rats were either untreated (n = 8) or treated (n = 10) by intramyocardial injection of (111)In-labeled BMSCs. Early distribution of (111)In-BMSCs within the MI target was evidenced by dual (111)In/(99m)Tc pinhole SPECT 48 h later. Myocardial perfusion was serially monitored by (99m)Tc-sestamibi pinhole gated SPECT up to 3 mo after transplantation. RESULTS: Forty-eight hours after transplantation, (111)In-BMSCs were observed in all treated rats and in 18 of their 32 underperfused MI segments (<70% sestamibi uptake before transplantation). During the subsequent 3-mo follow up, the perfusion of MI segments worsened in untreated rats (absolute change in sestamibi uptake, -3% +/- 3%; P < 0.05) but improved in treated rats (+4% +/- 7%; P < 0.05). This perfusion improvement was unrelated to the initial detection of (111)In-BMSCs (+2% +/- 6% in segments with (111)In-BMSCs vs. +5% +/- 7% in those without; not statistically significant) but was strongly associated with less severe perfusion defects before transplantation (+6% +/- 6% in segments with 60% 70% sestamibi uptake [n = 19] vs. -1% +/- 6% in those with <60% uptake [n = 13]; P = 0.003). CONCLUSION: When BMSCs are injected within chronic MI, perfusion enhancement predominates in the MI areas showing a high enough residual perfusion before treatment but not in those of the initial cell engraftment, giving evidence of dependency on the perfusion and metabolic environment at implantation sites. PMID- 17332619 TI - PET imaging of regional 18F-FDG uptake and lung function after cigarette smoke inhalation. AB - Cigarette smoke is thought to promote local lung inflammation that leads to lung dysfunction. Lung neutrophilic inflammation is known to result in increased pulmonary uptake of (18)F-FDG. Using a sheep model of localized exposure to cigarette smoke, in this study we tested whether PET-imaged changes in regional intrapulmonary distribution of (18)F-FDG uptake are related to changes in regional lung function as assessed with the infused (13)NN-saline method. METHODS: Five anesthetized, mechanically ventilated sheep were exposed to unilateral inhalation of smoke from 10 tobacco cigarettes while the contralateral lung was ventilated with smoke-free gas. Two hours after the exposure, regional gas content was measured from a transmission scan; regional ventilation, perfusion, and shunt were measured from the kinetics of (13)NN-saline; and regional (18)F-FDG influx constant (K(i)) was calculated with the Patlak algorithm applied at a voxel-by-voxel level. RESULTS: K(i) was higher and more heterogeneous in the smoke-exposed lungs than in the control lungs (P < 0.05). Spatial heterogeneity of K(i) and impairment in regional lung function were quite variable among animals despite similar levels of smoke exposure. However, increases in mean K(i) correlated linearly with its spatial heterogeneity (Spearman correlation, r(s) = 0.94), and the highest levels of regional K(i) in smoke-exposed lungs and control lungs correlated with regional shunt fraction (r(s) = 0.78). Also, the heterogeneity of the ventilation-perfusion (V/Q) distribution of the smoke-exposed lungs was 10 times greater than that of the control lungs but correlated strongly with that of the control lungs (r = 0.998). CONCLUSION: Substantial interanimal variability and spatial heterogeneity in lung function and (18)F-FDG uptake seem to characterize the response to smoke exposure. The highest levels of local (18)F-FDG uptake were associated with differences in V/Q matching and shunt fraction among animals. The data also suggest that preexisting heterogeneity in V/Q could have been responsible for the large interanimal variability by affecting the heterogeneity and strength of the acute response to smoke inhalation. PMID- 17332620 TI - 18F-fluoroacetate: a potential acetate analog for prostate tumor imaging--in vivo evaluation of 18F-fluoroacetate versus 11C-acetate. AB - PET with (11)C-acetate ((11)C-ACE) has a high sensitivity for detection of prostate cancer and several other cancers that are poorly detected with (18)F FDG. However, the short half-life (20.4 min) of (11)C limits the general availability of (11)C-ACE. (18)F-Fluoroacetate ((18)F-FAC) is an analog of acetate with a longer radioactive half-life ((18)F = 110 min). This study was undertaken to assess the potential usefulness of (18)F-FAC as a prostate tumor imaging agent. METHODS: We developed an efficient radiosynthesis for (18)F-FAC, which has already been adapted to a commercial synthesizer. Biodistribution studies of (18)F-FAC were compared with (11)C-ACE in normal Sprague-Dawley male rats and CWR22 tumor-bearing nu/nu mice. We also performed a small-animal PET study of (18)F-FAC in CWR22 tumor-bearing nu/nu mice and a whole-body PET study in a baboon to examine defluorination. RESULTS: We obtained (18)F-FAC in a radiochemical yield of 55% +/- 5% (mean +/- SD) in approximately 35 min and with a radiochemical purity of >99%. Rat biodistribution showed extensive defluorination, which was not observed in the baboon PET, as indicated by the standardized uptake values (SUVs) (SUVs of iliac bones and femurs were 0.26 and 0.3 at 1 h and 0.22 and 0.4 at 2 h, respectively). CWR22 tumor-bearing nu/nu mice showed tumor uptake (mean +/- SD) of 0.78 +/- 0.06 %ID/g (injected dose per gram of tissue) for (11)C-ACE versus 4.01 +/- 0.32 %ID/g for (18)F-FAC. For most organs-except blood, muscle, and fat-the tumor-to-organ ratios at 30 min after injection were higher with (18)F-FAC, whereas the tumor-to-heart and tumor-to prostate ratios were similar. CONCLUSION: All of these data indicate that (18)F FAC may be a useful alternative to (11)C-ACE tracer for the detection of prostate tumors by PET. PMID- 17332621 TI - Melanoma imaging with pretargeted bivalent bacteriophage. AB - Random bacteriophage (phage) display peptide libraries have traditionally been used for the selection of clones that bind specific tissues, tumors, and antigens. However, once the targeting peptide is synthetically produced, it often displays a lower affinity than the original phage because of a lack of avidity effects and removal from the virion surface. We hypothesized that multivalent bifunctional phage displaying peptides that target novel molecular biomarkers would facilitate the in vivo imaging of cancer. This study provides proof of principle for the use of phage displaying multiple melanocortin-1 receptor-homing peptides for the pretargeting and subsequent imaging of murine melanomas in vivo. METHODS: A 2-step melanoma pretargeting-imaging system was developed by first generating and biotinylating phage that displayed up to 5 copies of alpha melanocyte-stimulating hormone (alpha-MSH) peptide analogs. Second, streptavidin was conjugated to diethylenetriaminepentaacetic acid for the purpose of radiolabeling with (111)In. RESULTS: The specificity of the MSH2.0 phage for the B16-F1 melanoma was demonstrated both in vitro and in vivo. In vitro micropanning assays with phage at inputs of 10(7) and 10(6) transducing units per milliliter resulted in approximately 200- and approximately 1,000-fold-greater recovery of the MSH2.0 phage over the background, respectively. In vivo distribution studies indicated that melanoma uptake values were 2.6 +/- 1.1, 0.6 +/- 0.2, and 1.0 +/- 0.1 (mean +/- SD) percentage injected dose per gram at 0.5, 6, and 24 h after the injection of (111)In-radiolabeled streptavidin ((111)In-SA). The accumulation of radioactivity within the tumor was 1.8 times greater for the biotinylated MSH2.0 phage than for the biotinylated wild-type phage. These data, combined with reduction by 2.4-fold through competition with a nonradiolabeled alpha-MSH peptide analog, indicated the specific targeting of melanoma tumors in vivo. SPECT/CT image analysis of B16-F1 melanoma-bearing mice showed that intravenously injected biotinylated alpha-MSH phage were retained within melanoma tumors at 4 h after injection of (111)In-SA. CONCLUSION: This study demonstrated the use of multivalent bifunctional phage in a 2-step pretargeting-imaging system. PMID- 17332622 TI - Thermal dosimetry predictive of efficacy of 111In-ChL6 nanoparticle AMF--induced thermoablative therapy for human breast cancer in mice. AB - Antibody (mAb)-linked iron oxide nanoparticles (bioprobes) provide the opportunity to develop tumor specific thermal therapy (Rx) for metastatic cancer when inductively heated by an externally applied alternating magnetic field (AMF). To evaluate the potential of this Rx, in vivo tumor targeting, efficacy, and predictive radionuclide-based heat dosimetry were studied using (111)In-ChL6 bioprobes (ChL6 is chimeric L6) in a human breast cancer xenograft model. METHODS: Using carbodiimide, (111)In-DOTA-ChL6 (DOTA is dodecanetetraacetic acid) was conjugated to polyethylene glycol-iron oxide-impregnated dextran 20-nm particles and purified as (111)In-bioprobes. (111)In doses of 740-1,110 kBq (20 30 muCi) (2.2 mg of bioprobes) were injected intravenously into mice bearing HBT3477 human breast cancer xenografts. Pharmacokinetic (PK) data were obtained at 1, 2, 3, and 5 d. AMF was delivered 72 h after bioprobe injection at amplitudes of 1,410 (113 kA/m), 1,300 (104 kA/m), and 700 (56 kA/m) oersteds (Oe) at 30%, 60%, and 90% "on" time (duty), respectively, and at 1,050 Oe (84 kA/m) at 50% and 70% duty over the 20-min treatment. Treated and control mice were monitored for 90 d. Tumor total heat dose (THD) from activated tumor bioprobes was calculated for each Rx group using (111)In-bioprobe tumor concentration and premeasured particle heat response to AMF amplitudes. Tumor growth delay was analyzed by Wilcoxon rank sum comparison of time to double, triple, and quintuple tumor volume in each group, and all groups were compared with the controls. RESULTS: Mean tumor concentration of (111)In-bioprobes at 48 h was 14 +/- 2 percentage injected dose per gram; this concentration 24 h before AMF treatment was used to calculate THD. No particle-related toxicity was observed. Toxicity was observed at the highest AMF amplitude-duty combination of 1,300 Oe and 60% over 20 min; 6 of 10 mice died acutely. Tumor growth delay occurred in all of the other groups, correlated with heat dose and, except for the lowest heat dose group, was statistically significant when compared with the untreated group. Electron microscopy showed (111)In-bioprobes on tumor cells and cell death by necrosis at 24 and 48 h after AMF. CONCLUSION: mAb-guided bioprobes (iron oxide nanoparticles) effectively targeted human breast cancer xenografts in mice. THD, calculated using empirically observed (111)In-bioprobe tumor concentration and in vitro nanoparticle heat induction by AMF, correlated with tumor growth delay. PMID- 17332623 TI - Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel. AB - Vascular endothelial growth factor A (VEGF-A) and its receptors, Flt-1/FLT-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2), are key regulators of tumor angiogenesis and tumor growth. The purpose of this study was to determine the antiangiogenic and antitumor efficacies of a vasculature-targeting fusion toxin (VEGF(121)/rGel) composed of the VEGF-A isoform VEGF(121) linked with a G(4)S tether to recombinant plant toxin gelonin (rGel) in an orthotopic glioblastoma mouse model by use of noninvasive in vivo bioluminescence imaging (BLI), MRI, and PET. METHODS: Tumor-bearing mice were randomized into 2 groups and balanced according to BLI and MRI signals. PET with (64)Cu-1,4,7,10-tetraazacyclododedane N,N',N'',N'''-tetraacetic acid (DOTA)-VEGF(121)/rGel was performed before VEGF(121)/rGel treatment. (18)F-Fluorothymidine ((18)F-FLT) scans were obtained before and after treatment to evaluate VEGF(121)/rGel therapeutic efficacy. In vivo results were confirmed with ex vivo histologic and immunohistochemical analyses. RESULTS: Logarithmic transformation of peak BLI tumor signal intensity revealed a strong correlation with MRI tumor volume (r = 0.89, n = 14). PET with (64)Cu-DOTA-VEGF(121)/rGel before treatment revealed a tumor accumulation (mean +/- SD) of 11.8 +/- 2.3 percentage injected dose per gram at 18 h after injection, and the receptor specificity of the tumor accumulation was confirmed by successful blocking of the uptake in the presence of an excess amount of VEGF(121). PET with (18)F-FLT revealed significant a decrease in tumor proliferation in VEGF(121)/rGel-treated mice compared with control mice. Histologic analysis revealed specific tumor neovasculature damage after treatment with 4 doses of VEGF(121)/rGel; this damage was accompanied by a significant decrease in peak BLI tumor signal intensity. CONCLUSION: The results of this study suggest that future clinical multimodality imaging and therapy with VEGF(121)/rGel may provide an effective means to prospectively identify patients who will benefit from VEGF(121)/rGel therapy and then stratify, personalize, and monitor treatment to obtain optimal survival outcomes. PMID- 17332624 TI - Biodistribution of the fatty acid analogue 18F-FTHA: plasma and tissue partitioning between lipid pools during fasting and hyperinsulinemia. AB - Alterations of free fatty acid (FA) metabolism in several organs are implicated in the pathogenesis of chronic disorders. The aim of this study was to investigate the biodistribution and partitioning of the FA analog, 14(R,S)-(18)F fluoro-6-thia-heptadecanoic acid ((18)F-FTHA), across different lipid pools in plasma and in metabolically important organs and its response to insulin. METHODS: Eight anesthetized pigs were studied during fasting or euglycemic insulin stimulation. Plasma samples from the carotid artery, hepatic vein, and portal vein were collected at 10 and 40 min after (18)F-FTHA injection via indwelling catheters. The animals were then sacrificed and tissue biopsies rapidly obtained from the heart, brain, liver, subcutaneous and visceral fat, pancreas, intestine, and skeletal muscle. Radioactivity was assessed in the FA, phospholipid, and triglyceride or glycerol ester pools. RESULTS: The tissue-to plasma intact (18)F-FTHA ratio was high in all tissues, with the highest values being in the heart and liver; (18)F-FTHA accumulated in the brain to a significant extent. Hyperinsulinemia was associated with higher plasma (18)F-FTHA clearance (P < 0.05) and lower labeled triglyceride appearance (P or=0.15 Gy, with a 50% reduction at 1.5 Gy, compared with the results observed for nonirradiated control cells. (3)H Thymidine incorporation was already statistically significantly reduced at absorbed doses of 0.01-0.1 Gy, but 0.15-0.3 Gy did not affect DNA synthesis. However, absorbed doses of >or=1 Gy again resulted in reduced DNA synthesis. A 50% reduction was obtained at 4 Gy. Total DNA measurements revealed a statistically significant reduction in cell numbers at 8 Gy. CONCLUSION: The lowest absorbed dose from (131)I that reduced iodide transport was 0.15 Gy. Because stunning was found at low absorbed doses, it might occur for (131)I treatment not only of thyroid cancer but also of thyrotoxicosis. On the basis of differences in dose responses, radiation-induced thyroid stunning and cell cycle arrest may be independent phenomena. PMID- 17332628 TI - Submillimeter total-body murine imaging with U-SPECT-I. AB - Recently, we launched a stationary SPECT system (U-SPECT-I) dedicated to small animal imaging. A cylinder with 75 gold micropinhole apertures that focus on a mouse organ was used to maximize the detection yield of gamma-photons. Image resolutions of approximately 0.45 and 0.35 mm could be achieved with 0.6- and 0.3 mm pinholes, respectively. Here, we present a combined acquisition and reconstruction strategy that allowed us to perform full-body imaging with U-SPECT I. METHODS: The bed was stepped in the axial and transaxial directions so that the pinholes collected photons from the entire animal (scanning focus method, or SFM). Next, a maximum-likelihood expectation maximization algorithm exploited all projections simultaneously to reconstruct the entire volume sampled. The memory required for image reconstruction was dramatically reduced by using the same transition submatrix for each of the bed positions. This use of the same submatrix was possible because the submatrix acted on subvolumes that were shifted during reconstruction to match the corresponding location of the focus. RESULTS: In all cases, SFM clearly improved on the method that involves stitching separate reconstructions of subvolumes obtained from the different bed positions. SFM suffered less from noise, streak artifacts, and improper background activity. In a mouse-sized phantom containing a capillary-resolution insert, sets of radioactively filled capillaries as small as 0.45 mm separated by 0.45 mm could be distinguished. Total-body mouse bone imaging using (99m)Tc-hydroxymethylene diphosphonate showed that uptake in very small structures, such as parts of the vertebral processes, could be distinguished. CONCLUSION: In addition to providing ultra-high-resolution images of mouse organs, focusing SPECT pinhole systems are also suitable for submillimeter-resolution total-body imaging of mice. PMID- 17332629 TI - Genomic DNA isolation from different biological materials. AB - A comprehensive collection of different methods for extracting high-quality genomic DNA from gram-positive and -negative bacteria and fungal mycelium and spores is described in this chapter. Special care has been taken in describing the ideal ratio of biological material to chemical reagents for an efficient extraction of genomic DNA, and in stating the appropriate application in molecular biology protocols (e.g., PCR or genomic DNA library-cloning quality). PMID- 17332630 TI - Extraction of plant RNA. AB - Optimal sampling procedures for sampling plant tissue for RNA extractions are outlined in this chapter. To extract RNA, kits supplied from biotechnology companies are appropriate, but some procedures will not work with particular plant tissues. Two alternative methods are supplied for troublesome material. Basic methods to check RNA quantity and, more particularly, RNA quality before use are supplied. PMID- 17332631 TI - Overview of hybridization and detection techniques. AB - A misconception regarding the sensitivity of nonradioactive methods for screening genomic DNA libraries often hinders the establishment of these environmentally friendly techniques in molecular biology laboratories. Nonradioactive probes, properly prepared and quantified, can detect DNA target molecules to the femtomole range. However, appropriate hybridization techniques and detection methods should also be adopted for an efficient use of nonradioactive techniques. Detailed descriptions of genomic library handling before and during the nonradioactive hybridization and detection are often omitted from publications. This chapter aims to fill this void by providing a collection of technical tips on hybridization and detection techniques. PMID- 17332632 TI - Checkerboard DNA-DNA hybridization technology using digoxigenin detection. AB - Checkerboard DNA-DNA hybridization (CKB) is a technique that provides a simultaneous quantitative analysis of 40 microbial species against up to 28 mixed microbiota samples on a single membrane; using digoxigenin (DIG)-labeled, whole genome DNA probes. Developed initially to study the predominantly gram-negative dental plaque microorganisms involved in periodontitis, we modified the probe species composition to focus on putative pathogens involved in the development of dental caries. CKB analysis is applicable to species from other biodiverse ecosystems and to a large number of samples. The major limitations are that high quality DNA is required for the preparation of DIG-labeled probes and standards, and that probe specificity requires careful evaluation. Overall, CKB analysis provides a powerful ecological fingerprint of highly biodiverse microbiota based on key cultivable bacteria. PMID- 17332633 TI - Nonradioactive northern and Southern analyses from plant samples. AB - Several specific problems are encountered when nonradioactive detection methods are used in conjunction with plant nucleic acids. In this chapter, we describe protocols for the isolation of DNA and RNA from plant leaves and the preparation of probe molecules by either PCR or in vitro transcription with different haptens. Furthermore, standard conditions and possible modifications for hybridization and detection of probes are given. PMID- 17332634 TI - Screening a BAC library with nonradioactive overlapping oligonucleotide (overgo) probes. AB - Comparative mapping has been the primary approach for analyzing genomes of divergent species because gene linkage is often conserved over evolutionary time, a phenomenon known as synteny. Comparisons are based on computational detection of orthologous sequences between species. Small overlapping oligonucleotide (overgo) probes, consisting of two self-annealing oligonucleotides at the 3'-end, are filled in with labeled deoxynucleotides. Overgo probes are designed against highly conserved regions between two genomes, at regular intervals (30-40 kbp). All methodologies reported to date have used radioactive dATP and dCTP to label overgo probes. We report a nonradioactive labeling protocol to produce digoxigenin-labeled overgo probes for high-throughput screening of the Actinidia chinensis bacterial artificial chromosome library. PMID- 17332635 TI - Direct in-gel hybridization of DNA with digoxigenin-labeled probes. AB - In-gel hybridization with digoxigenin (DIG)-labeled probes has been shown to detect complementary DNA sequences in dried agarose gels. Gels dried at room temperature or at 55 degrees C in an oven do not show detectable changes in the sensitivity of detection. However, gels dried under vacuum seem to lose the sensitivity by approx 8- to 10-fold. In-gel hybridization after blotting high molecular weight T7 DNA (40 kbp) onto nylon membranes has been demonstrated to transfer the DNA to the membrane inefficiently. In-gel hybridization of DIG labeled probes with the complementary DNA sequences has been determined to detect as little as 0.05 ng of 40-kbp T7 DNA and single copies of the erythromycin resistance marker gene ermA. Nonradioactive in-gel hybridization provides better quantitation of nucleic acids than filter hybridization in Southern and Northern blot analysis. PMID- 17332636 TI - In situ hybridization of termite microbes. AB - In situ hybridization is one of the most direct and reliable ways to ascertain the origin of the gene from complex mixed cellular systems. This method is essential for studying communities of uncultured microorganism in their natural ecosystem. In this chapter, we introduce our protocols for the in situ hybridization of the messenger RNA of uncultured symbiotic protists of termite hindgut and the ribosomal RNA of the symbiotic bacteria of the protists using nonradioactive labeling protocols. We hope that you will find these protocols useful in your own work to unravel the complex functions and to discover new organisms in the ecosystem. PMID- 17332637 TI - RNA electrophoretic mobility shift assay using a fluorescent DNA sequencer. AB - The RNA electrophoretic mobility shift assay is a simple and rapid method for visualizing the existence of specific RNA-protein interaction. We have developed a useful method for the detection of mRNA-binding proteins using fluorescence labeled synthetic RNA. In this method, RNA was prepared by in vitro transcription using Texas Red-labeled nucleotides. This method has higher resolution than the conventional method using slab gels, is safer, and provides results rapidly because of the use of fluorescence detection. PMID- 17332638 TI - Comparative quantitation of mRNA expression in the central nervous system using fluorescence in situ hybridization. AB - In situ hybridization to messenger RNA (mRNA) in complex tissues, such as the brain, allows the localization of gene expression to functionally distinct regions. It has been difficult to measure relative changes in gene expression within these regions because of the poor cellular resolution afforded by radioactively labeled probes and problems associated with densitometric analysis by counting silver grain deposition. Fluorescence in situ hybridization, using probes directly labeled with dyes that exhibit high quantum yield, provides both high-resolution localization of mRNA and high sensitivity for detection of hybridized probe. Digital image capture of fluorescence is readily amenable to densitometric analysis, thereby allowing relative quantification of mRNA expression in single cells or discrete brain nuclei. In this chapter, we describe protocols suitable for measuring relative changes in gene expression within individual cells of brain sections mounted on glass slides. PMID- 17332639 TI - Visualization of gene expression by fluorescent multiplex reverse transcriptase PCR amplification. AB - Many developmental and physiological analyses, population studies, and diagnostic tests can be performed by simply determining the presence or absence of a limited number of gene products. Here, we describe a rapid and sensitive procedure, based on the reverse transcription of total RNA samples followed by the co amplification of specific complementary DNA molecules, for the simultaneous detection of different transcripts. Multiplex PCR amplification products are obtained in a single reaction mix containing several primer pairs, each of which includes a fluorescently labeled oligonucleotide; the amplification products are finally electrophoresed in an automated DNA sequencer controlled by fragment analysis software. The electropherograms obtained in this way allow a semiquantitative and efficient visualization of gene expression. PMID- 17332640 TI - Fluorescence in situ hybridization for the identification of environmental microbes. AB - This chapter presents a protocol for the phylogenetic identification of microorganisms in environmental samples (water and sediments) by means of fluorescence in situ hybridization (FISH) with ribosomal RNA-targeted oligonucleotide probes and signal amplification (catalyzed reporter deposition [CARD]). The FISH probes are labeled with the enzyme, horseradish peroxidase (HRP). A subsequent deposition of fluorescently labeled tyramides results in substantially higher signal intensities of target cells than after FISH with probes directly labeled with fluorochromes. Sample preparation and cell permeabilization strategies for various microbial cell wall types are discussed. The custom labeling of tyramides with different fluorochromes is described. A sequential multicolor CARD-FISH protocol is outlined for the simultaneous detection of different phylogenetic groups. PMID- 17332641 TI - Introduction to kinetic (real-time) PCR. AB - Kinetic or real-time PCR continues to develop at a rapid rate since its development in the early 1990s. New applications are continually being found for this technique and it is replacing conventional PCR in many fields because of its speed, reduced hands-on time, and because the closed-tube format greatly reduces the chance of reaction contamination. This chapter covers the basis of kinetic PCR and also discusses some of the parameters that need to be considered even before the actual amplification--such as nucleic acid extraction and the complementary DNA synthesis step required in the instance of gene expression studies. PMID- 17332642 TI - Validation of short interfering RNA knockdowns by quantitative real-time PCR. AB - RNA interference (RNAi) is a natural mechanism, that is triggered by the introduction of double-stranded RNA into a cell. The long double-stranded RNA is then processed into short interfering RNA (siRNA) that mediates sequence-specific degradation of homologous transcripts. This phenomenon can be exploited to experimentally trigger RNAi and downregulate gene expression by transfecting mammalian cells with synthetic siRNA. Thus, siRNAs can be designed to specifically silence the expression of genes bearing a particular target sequence. In this chapter, we present methods and procedures for validating the effects of siRNA-based gene silencing on target gene expression. To illustrate our approach, we use examples from our analysis of a Cancer Gene Library of 278 siRNAs targeting 139 classic oncogenes and tumor suppressor genes (Qiagen Inc., Germantown, MD). Specifically, this library was used for high-throughput RNAi phenotype analysis followed by gene expression analysis to validate gene silencing for siRNA that produced a phenotype. Methods and protocols are presented that illustrate how sequence-specific gene silencing of effective siRNAs are analyzed and validated by quantitative real-time PCR assays to measure the extent of target gene silencing, as well as effects on various gene expression end points. PMID- 17332643 TI - Real-time quantitative PCR as an alternative to Southern blot or fluorescence in situ hybridization for detection of gene copy number changes. AB - Changes in copy number of genes contribute to the pathogenesis of various genetic disorders and cancer. The status of a gene has not only diagnostic value but sometimes directs treatment stratification. Although, for many years, Southern blot and fluorescence in situ hybridization were the standard methods for the detection of deletion, duplication, or amplification of a gene, both methods have their own important limitations. Recently, realtime quantitative PCR has proven to be a good alternative for the detection of gene copy number changes. Its main advantages are the large dynamic range of accurate quantification, the absence of post-PCR manipulations, its high-throughput screening capacity and degree of automation, and the possibility to perform the assay on minimal amounts of sample DNA in just a few hours of time. In this chapter, we outline the procedure of how to develop an assay for the detection of gene copy number changes for your gene of interest. We illustrate the approach by describing a validated assay for the detection of germline VHL exon deletions and for determination of MYCN copy numbers in tumor samples. PMID- 17332644 TI - Design and work-up of a new molecular diagnostic assay based on real-time PCR. AB - In routine molecular diagnostics, real-time PCR has made a major impact because of the faster time to the result; decreased hands-on time; and virtual elimination of the major issue in the early days of PCR, sample contamination from previously amplified DNA. The shorter time to the result for a real-time PCR assay means that a new diagnostic application may be developed relatively quickly. This chapter discusses the fluorescent chemistries typically used in molecular diagnostic applications and the additional features, such as internal controls, which are highly desirable in these assays. After an assay has been developed, the assay's performance must also be evaluated before the assay can be implemented in the testing laboratory. PMID- 17332645 TI - Real-time PCR fluorescent chemistries. AB - There are more than a dozen formats available for the fluorescent detection of amplified DNA in kinetic (real-time) PCR. These chemistries are adaptable to most real-time PCR instruments and may offer benefits over the usual manufacturer recommended chemistries for the instrument. The most popular chemistries are the generic dye, SYBR Green I, TaqMan, and hybridization probes. However, there are now new dyes being reported with superior fluorescent detection and product resolution; as well as new probe formats that may offer advanced multiplexing opportunities for quantification and genotyping. PMID- 17332646 TI - Microarrays: an overview. AB - Gene expression microarrays are being used widely to address a myriad of complex biological questions. To gather meaningful expression data, it is crucial to have a firm understanding of the steps involved in the application of microarrays. The available microarray platforms are discussed along with their advantages and disadvantages. Additional considerations include study design, quality control and systematic assessment of microarray performance, RNA-labeling strategies, sample allocation, signal amplification schemes, defining the number of appropriate biological replicates, data normalization, statistical approaches to identify differentially regulated genes, and clustering algorithms for data visualization. In this chapter, the underlying principles regarding microarrays are reviewed, to serve as a guide when navigating through this powerful technology. PMID- 17332647 TI - Oligonucleotide microarrays for the study of coastal microbial communities. AB - DNA microarrays are well suited as a tool for analyzing functional gene diversity as well as community composition in aquatic environments. Microarrays allow for the semi-quantitative characterization of target genes by means of specific hybridization of labeled target gene sequences, amplified from the environment, to the corresponding oligonucleotide probes on the slide. Specificity and sensitivity are determined by the probe design. In their current implementation, environmental DNA microarrays are useful for analyzing microbial communities as well as for analyzing the presence of functional genes involved in larger biogeochemical processes, such as nitrogen cycling. Here, we lay out a basic protocol to analyze genes in the environment, which can be applied to most target genes of interest. PMID- 17332648 TI - Polio eradication & the future for other programmes: situation analysis for strategic planning in India. PMID- 17332649 TI - The CRASH-2 trial of an antifibrinolytic agent in traumatic haemorrhage: an international collaboration. PMID- 17332650 TI - Are we heading in the right direction? PMID- 17332651 TI - Elevation of tumour marker CA-125 in serum & body fluids: interpret with caution. PMID- 17332652 TI - Quo vadis, expanded programme on immunization? PMID- 17332653 TI - The therapeutic potential of human embryonic stem cells. AB - Due to lack of suitable organ donors, future degenerative diseases and traumas could be treated with stem cell engraftment. To do this, large numbers of cells must be grown and maintained in culture. These cells must also be capable to differentiate into all the cells of the body. Embryonic stem cells fulfill many of the necessary criteria for clinical translation for use in therapeutic transplantation for a myriad of diseases. There are still many issues including immunological, cell cycling and differentiation that must be overcome for them to reach their potential use in the clinical arena. PMID- 17332654 TI - Role of cancer antigen-125 from pleural & ascitic fluid samples in non malignant conditions. AB - BACKGROUND & OBJECTIVE: CA-125, an ovarian tumor marker is known to increase in non malignant conditions such as tubercular and non tubercular pleuritis and ascites. We undertook this study to evaluate non-specific rise in CA-125 levels in conditions associated with pleural effusion and ascites and also to understand the mechanism of its secretion. METHODS: CA-125 levels in 38 pleural and 46 ascitic fluid samples from non malignant cases and 10 blood samples from pulmonary tuberculosis cases were estimated by ELISA. The ascitic fluid samples were collected from cases of bacterial peritonitis, tuberculosis, hepatitis, cirrhosis of other aetiology and pleural fluid samples were from cases of tubercular, pyogenic, cardiomegaly and other conditions. RESULTS: Both ascitic and pleural fluid samples (transudative and exudative) showed elevated CA- 125 levels. The CA-125 levels were significantly higher in ascitic fluid samples than in pleural fluid samples. INTERPRETATION & CONCLUSION: Our findings showed that elevated levels of CA-125 in pleural and ascitic fluid could be because of varied aetiologies which need to be ruled out before considering malignancy. Peritoneum has a greater capacity to secrete CA-125 than the pleural epithelium and the secretion occurs following inflammation or mechanical distress. Pulmonary tuberculosis as a closed lesion without involvement of pleural epithelium does not evoke high CA-125 release. PMID- 17332655 TI - Health infrastructure & immunization coverage in rural India. AB - BACKGROUND & OBJECTIVE: Immunization coverage in India is far from complete with a disproportionately large number of rural children not being immunized. We carried out this study to examine the role of health infrastructure and community health workers in expanding immunization coverage in rural India. METHODS: The sample consisted of 43,416 children aged 2-35 months residing in rural India from the National Family Health Surveys (NFHS) conducted in 1993 and 1998. We estimated separate multinomial logit regression models for polio and non polio vaccines that estimated the probability that a child would receive "no cover," "some cover" or "full age-appropriate cover." The key measure of health infrastructure was a hierarchical variable that assigned each child to categories (no facility, dispensary or clinic, sub-centre, primary health care centre, and hospital) based on the best health facility available in the child's village. We also included variables capturing the availability of various types of community health workers in the village and other health infrastructure. RESULTS: While there was under-provision of rural health infrastructure, our results showed that the availability of health infrastructure had only a modest effect on immunization coverage. Larger and better-equipped facilities had bigger effects on immunization coverage. The presence of community health workers in the village was not associated with increased immunization coverage. INTERPRETATION & CONCLUSION: Our findings suggest that expanding the availability of fixed health infrastructure is unlikely to achieve the goal of universal coverage. Reforming community outreach programmes might be better strategy for increasing immunization coverage. PMID- 17332656 TI - Expression of insulin like growth factor binding protein-5 in drug induced human gingival overgrowth. AB - BACKGROUND & OBJECTIVE: Insulin like growth factor binding proteins (IGFBPs) control the distribution, function and activity of insulin like growth factors (IGFs) in various cells, tissues and body fluids, thereby modulating their metabolic and mitogenic effects. IGFBP-5, the most conserved IGFBP, can function through IGF or directly play a role in fibrosis. Cyclosporine A (CsA) widely used in organ transplant patients, often causes various side effects including gingival fibrotic overgrowth. This study was carried out to assess the mRNA expression of IGFBP-5 in healthy human gingival, chronic periodontitis and CsA induced gingival overgrowth tissues. METHODS: Total RNA was isolated from gingival tissues collected from eight patients with chronic periodontitis, eight patients with CsA induced gingival outgrowth and an equal number of healthy individuals, and subjected to reverse transcription (RT)-PCR for IGFBP-5 gene expression. RESULTS: CsA induced gingival overgrowth tissues expressed increased IGFBP-5 mRNA compared to control and chronic periodontitis. INTERPRETATION & CONCLUSION: Increased mRNA expression of IGFBP-5 in CsA induced gingival outgrowth tissues may be associated with increased collagen synthesis, thereby promoting fibrogenesis. PMID- 17332657 TI - Acceptance of HIV-1 education & voluntary counselling/testing by & seroprevalence of HIV-1 among, pregnant women in rural south India. AB - BACKGROUND & OBJECTIVE: Since the first report of HIV-1 infection in Tamil Nadu, India, HIV-1 seroprevalence in India has increased steadily. Though interventions to prevent mother-to-child transmission (MTCT) are available, their implementation is a significant challenge. Therefore, among pregnant women in rural Tamil Nadu, the acceptance of education regarding HIV-1 infection and transmission and, among a systematic sample, knowledge, attitudes, and beliefs; the acceptance of HIV-1 voluntary counselling and testing (VCT); and the seroprevalence of HIV-1 infection as well as risk factors for seropositivity were assessed. METHODS: Pregnant women registered in the antenatal clinics at Namakkal District Hospital and Rasipuram Government Hospital, Tamil Nadu, India, were offered an educational session regarding HIV-1 infection and transmission. HIV-1 VCT, with informed consent, was offered. Positive results with HIV-1 rapid testing were confirmed with HIV-1 ELISA and Western blot assays. With informed consent, a systematic sample of the study population was asked to participate in pre- and posteducation assessments. Chi-square tests were used to evaluate HIV-1 risk factors. RESULTS: The educational session as well as VCT were well accepted by rural, pregnant, HIV-1- infected women. Of 3722 women registered for antenatal care at the two hospitals over a one year period, 3691 (99.2%) agreed to participate in the educational session and 3715 (99.8%) had VCT [74 had confirmed HIV-1 infection [seroprevalence: 2.0% (95% confidence interval (95%CI): 1.6%, 2.5%)]]. Of 759 eligible women, a systematic sample of 757 (99.7%) women participated in the pre- and post-education assessments. Although baseline knowledge regarding HIV-1 was limited, a highly significant improvement in such knowledge was observed (P<0.0001 for all comparisons of changes in knowledge, attitudes, and beliefs measured before and immediately after the educational session). The median per cent of correct responses increased from 26.4 per cent before the educational session to 93.8 per cent afterwards. Women whose husbands were long distance truck drivers were at increased risk of HIV-1 infection. Other factors associated with HIV-1 infection were clinical site (Namakkal District Hospital), a smaller number of persons in the household, being unmarried, and a history of previous surgeries. INTERPRETATION & CONCLUSION: The acceptability of education and of VCT among antenatal clinic attendees in this study was encouraging. However, the relatively high seroprevalence highlights the spread of HIV-1 from high risk groups to the general population and emphasizes the need for primary prevention of HIV-1 infection among adolescent girls and women of reproductive age in India. PMID- 17332658 TI - Operational feasibility of rapid diagnostic kits & blister packs use for malaria control in high transmission areas of Orissa & Chhattisgarh. AB - BACKGROUND & OBJECTIVE: Early diagnosis and prompt treatment of cases with malaria are two important components of malaria control strategy. The independent assessment of the operational feasibility of rapid diagnostic kits and blister packs for malaria in some selected high transmission areas of Orissa and Chhattisgarh was done with the objectives to assess the knowledge and skills of the paramedical personnel and their acceptability by the paramedical personnel and the community, and to assess improvement in patients' health seeking behaviour. METHODS: The basic information regarding malaria situation, epidemiological divisions, distribution data of rapid diagnostic kits and blister packs, etc., was collected from State and district headquarters. The subcentres from the primary health centres/community health centres were selected on the basis of supply of rapid diagnostic kits and blister packs. The subcentres were visited and health personnel interviewed about their knowledge and skills on the use of rapid diagnostic kits and blister packs. A cross-sectional survey was conducted to assess the public opinion about rapid diagnostic kits and blister packs. RESULTS: We found that the paramedicals were well trained in the use of rapid diagnostic kits and blister pack administration and the acceptance was good by both paramedicals and general public. The compliance rate of radical treatment with blister packs was 100 per cent and no adverse events were reported. INTERPRETATION & CONCLUSION: Our findings showed that rapid diagnostic kits and blister packs under remote and inaccessible highly malarious areas can be introduced that will have significant impact in reducing malaria morbidity and mortality. PMID- 17332659 TI - Nested reverse transcription polymerase chain reaction for the detection of rubella virus in clinical specimens. AB - BACKGROUND & OBJECTIVE: Rubella virus (RV) is one of the leading causes of childhood blindness in India. In this study we applied an optimized nested reverse transcription polymerase chain reaction (nRT-PCR) to detect RV in clinical specimens. METHODS: nRT-PCR was optimized using total RNA extracted from standard strain of RV using nested sets of primers specific for E1 open reading frame. nRT-PCR was applied onto 30 lens aspirates and corresponding peripheral blood leucocytes of 30 infants with congenital (29)/ developmental (01) cataract. Serology for anti-RV IgG and IgM antibodies was done. RV isolation was attempted using Vero and SIRC cell cultures. RESULTS: Optimized nRT-PCR was specific for RV and sensitive to detect 10 fg of RV RNA. Among 30 patients, nRT-PCR detected presence of RV in lens aspirates of 6 (20%) and 4 corresponding leucocytes. RV was isolated from 3 (10%) lens aspirates (nRT-PCR positive) of the 30 patients. Sera of these 6 patients showed presence of anti-RV IgG and IgM in one, only anti RV IgG in 3 others and none in the other two. Of the remaining 24 patients, anti RV IgG was detected in 3 and no anti-RV IgM antibodies in others. INTERPRETATION & CONCLUSION: Findings of our study showed that the nRT-PCR was a more sensitive and rapid technique to detect RV from lens aspirates compared to conventional methods of virus isolation and serology. PMID- 17332660 TI - Plasmid distribution & antimicrobial susceptibility patterns of Acinetobacter genospecies from healthy skin of a tribal population in western India. AB - BACKGROUND & OBJECTIVE: Acinetobacter spp., the only Gram negative commensal found on human skin are emerging nosocomial pathogens, and are rapidly developing multiple drug resistance. Most studies in India and over the world are on clinical and environmental Acinetobacter isolates. The present investigation was undertaken to study plasmid distribution and antibiotic resistance profile of Acinetobacter genospecies isolated from healthy human skin of a tribal population from western India. METHODS: One hundred and eighteen strains of Acinetobacter spp. were isolated from healthy human skin and biochemically classified into nine genospecies. Plasmid profiles were determined using four standard methods with minor modifications and by a commercial kit. Molecular weights were determined by comparison with standard plasmids pUC19, pBR322, RP4 and molecular weight marker, V517. Antimicrobial susceptibility patterns of Acinetobacter genospecies to 30 antibiotics belonging to different groups was determined using Kirby Bauer method. RESULTS: All isolates, except two showed a maximum of three plasmids with molecular size 1.5 to 40 kb. Five different plasmid types were observed. Only eight strains had one or two stably maintained low molecular weight plasmids in addition to 40 kb plasmid seen in most of the strains. Quinolones and aminoglycosides were most active group followed by, cephalosporins and beta lactams. INTERPRETATION & CONCLUSION: Acinetobacter spp. isolated from the tribal skin flora had low number of plasmids as compared to clinical and environmental isolates. Acinetobacter spp. harbouring low molecular weight plasmids were found to be sensitive to most of the antibiotics tested suggesting these might be coding for some other novel properties or may be cryptic, whereas, those having 40 kb plasmid showed intermediate to low level resistance to some antibiotics. PMID- 17332661 TI - Prevalence & antimicrobial resistance pattern of extended spectrum beta-lactamase producing Klebsiella spp isolated from cases of neonatal septicaemia. AB - BACKGROUND & OBJECTIVE: Extended spectrum beta-lactamase (ESBL) producing Klebsiella spp led to serious concern about septicaemic neonates in neonatal intensive care units (NICU) due to high resistance against commonly used antimicrobial agents. Knowledge of disease burden and information on resistance to antimicrobials are required for proper management of such cases in NICUs. Here we report the prevalence and resistance pattern of ESBL producing Klebsiella spp isolated from cases of neonatal septicaemia at a tertiary care hospital from north India. METHODS: A total of 100 clinical isolates of Klebsiella spp isolated from 2995 blood samples of suspected cases of neonatal septicaemia were studied. Antimicrobial susceptibility was determined by Kirby- Bauer's disc diffusion method. All isolates were screened for ESBL production on the basis of inhibition zone against cephotaxime (<27 mm) and ceftazidime (<22 mm) and a breakpoint of minimum inhibitory concentration (MIC) (<2 microg/ml for cephotaxime and <8 microg/ml for cefpodoxime) by agar dilution method. Resistance pattern of ESBL producers and non-ESBL producers was compared. RESULTS: Of the 100 Klebsiella isolates, 58 were positive for ESBL production, which was much lower than 86.6 per cent reported in 2003. Almost all the isolates were sensitive to imipenam and meropenam. Drug resistance was found to be significantly more common in ESBL producing isolates than in non-ESBL producers. INTERPRETATION & CONCLUSION: We found that 56 per cent of Klebsiella spp isolates were ESBL producers. There is a need to carefully formulate therapeutic strategies to control infections in NICUs. The high percentage of drug resistance in ESBL producing Klebsiella spp suggests that routine detection of ESBL is required by reliable laboratory methods. PMID- 17332662 TI - BCG, tuberculin surveys & annual rate of tuberculosis infection in south India. PMID- 17332663 TI - Concern on prevalence of anaemia in pregnant & lactating women in India. PMID- 17332664 TI - Red cell adhesion in cerebral malaria. PMID- 17332665 TI - Assessment of vascular disease using arterial flow mediated dilatation. AB - Arterial endothelial dysfunction occurs at all stages of atherosclerosis, both preceding structural atherosclerosis changes, as well as predisposing to clinical events in late obstructive disease. Endothelial dysfunction is thus well correlated with risks of vascular events. Release of endothelial nitric oxide has been shown to be a key player in normal endothelial function. Endothelial function can be measured in the coronary arteries and peripheral vascular tree by intra-arterial infusion of substances that promote release of nitric oxide, but this method is limited by its invasive nature which limits its widespread use in asymptomatic subjects. Flow mediated dilatation is a non invasive ultrasound based method where arterial diameter is measured in response to an increase in shear stress, which causes release of nitric oxide from the endothelium and consequent endothelium dependent dilatation. Flow mediated dilatation has been shown to correlate with invasive measures of endothelial function, as well as with the presence and severity of the major traditional vascular risk factors. This noninvasive endothelial function testing has also demonstrated the potential reversibility of endothelial dysfunction by various strategies including cessation of smoking, weight loss in obese subjects, certain pharmacological agents (statins, ACE inhibitors), L-arginine and hormones. PMID- 17332666 TI - ESR techniques for the detection of nitric oxide in vivo as an index of endothelial function. AB - Plasma nitrite/nitrate levels reflect oxidation of formed nitric oxide (NO ) but are not indicative of endothelial nitric oxide synthase (eNOS) function due to interference by dietary nitrates and reactive oxygen species (ROS). Nitrosyl hemoglobin (NOHb), a metabolic product of nitric oxide, may better correlate with bioavailable NO but it may depend on the activity of different nitric oxide synthase (NOS) isoforms and may be affected by dietary nitrite/nitrate. We examined the correlation between vascular endothelial NO release and circulating blood levels of NOHb. We measured NOHb in blood using electron spin resonance (ESR) spectrometry and also quantified vascular production of NO using colloid Fe(DETC)(2) and ESR in mouse and human venous blood before and after treatment with the beta-blocker carvedilol. Exclusively the inhibition with L-NAME and not the treatment with the selective neuronal nitric oxide synthase (nNOS) inhibitor, N-AANG or with the selective inducible nitric oxide synthase (iNOS) inhibitor, 1400W, halved NOHb formation, which reflects the complete inhibition of NO release by aortic endothelium. The relationship between NOHb and NO production by the endothelium (0.23 microM NOHb to 3.73 microM/hour of NO per mg of aorta dry weight) was found to be identical for both C57Blk/6 mice and for mice with vascular smooth muscle-targeted expression of p22phox associated with strong increase in eNOS activity. Furthermore, the treatment of patients with cardiovascular diseases with carvedilol for 3 weeks increases up to 2 times the circulating NOHb concentration. These results demonstrate the important role of eNOS in the formation of circulating NOHb and suggest that NOHb can be used as a noninvasive marker of endothelial NO production in vivo. PMID- 17332667 TI - Asymmetric dimethylarginine (ADMA) a novel cardiovascular risk factor--evidence from epidemiological and prospective clinical trials. AB - There is a growing clinical evidence to support the hypothesis that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase is a new independent cardiovascular risk factor. ADMA mediates endothelial dysfunction in lipid disorders, coronary artery disease, chronic heart failure, diabetes mellitus and hypertension. The aim of this review was to summarize the latest evidence from epidemiological and prospective clinical trials and to emphasize the role of ADMAas a cardiovascular risk factor. PMID- 17332668 TI - Cytokines and adhesive molecules in detection of endothelial dysfunction. AB - Inflammatory response comprises endothelial dysfunction and atherosclerotic cascade. Adhesion molecules and cytokines are involved in both injury and reparative processes observed in an inflammed atherosclerotic vascular wall. As markers and mediators of endothelial dysfunction, adhesion molecules and cytokines seem to be a logical target of studying endothelial dysfunction, and especially because they participate not only in local but also in systemic response to injury. The present paper provides an overview of current clinical knowledge on the role of adhesive molecules and cytokines in endothelial dysfunction and overt atherosclerosis. Their participation in immune mechanisms of atherogenesis is analyzed with special consideration of the type of immune response. Clinical experience with adhesion molecules and cytokines related to risk factors, presentations and complications of atherosclerosis is also presented. The impact of revascularization procedures on adhesive molecules and cytokines levels as well as prognostic value of their assessment is summarized. PMID- 17332669 TI - Clinical aspects of assessment of endothelial function. AB - Prevention and treatment of atherosclerosis is an important priority. Measurement of endothelial function has been reported as a useful tool for atherosclerosis research. Endothelium appear to integrate the injury of commonly known risk factors and others, genetic and environmental as yet undiscovered. The assessment of endothelium-dependent vasodilation has emerged as indicator of endothelial health. Invasive methods examine coronary or brachial artery vasomotion in response to infusion of acetylcholine. Noninvasive ultrasound assessment of flow mediated vasodilation (FMD) of peripheral artery is more often used. However, despite its wide-spread use, there are technical and interpretive limitations of this technique. Recent studies have shown that the severity of endothelial dysfunction relates to cardiovascular risk. Endothelial function might be also used to monitor the effectiveness of risk reduction therapy. This article will review the growing literature in an effort to evaluate methods of assessment of endothelial function and its clinical utility. PMID- 17332670 TI - Impact of ageing on the measurement of endothelium-dependent vasodilation. AB - Two established methods to assess endothelium-dependent vasodilation in the peripheral circulation have been used in epidemiological research, the invasive forearm technique using intra-brachial infusion of acetylcholine (EDV) and flow mediated vasodilation (FMD) of the brachial artery using ultrasound Both EDV and FMD have proven to predict future cardiovascular events in patient populations and to be related to the major risk factors in large population studies, but both have methodological problems in the elderly. EDV is hampered by the fact that also endothelium-independent vasodilation (by nitroprusside infusion) is related to major cardiovascular risk factors and predict future cardiovascular events, so that little could be said about the specific function of the endothelium. FMD is markedly influenced by the impairment in brachial artery compliance seen even in the healthy elderly subjects, so that its use in the elderly has been questioned. The usefulness of other methods used in population studies, such as pulse wave analysis using a beta-2 receptor agonist as vasodilator and the hyperaemic blood flow velocity have to be further validated. PMID- 17332671 TI - Vascular prostaglandin synthesis: the early days. AB - Prostacyclin (PGI2) and thromboxane (TxA2) labile cyclooxygenase (COX) products via PGH2 were identified in biological fluids by the ingenious application of the principle of parallel pharmacological assays developed by John Vane. Either organ perfusates or circulating blood superfuse bioassay tissues arranged in a cascade. Tissues were selected based on specificity of responses to targeted eicosanoids. Additionally, PGI2 inhibited platelet aggregation, a finding that led to discovery of its critical anti-thrombotic activity at the blood-endothelial interface. The biological activities of PGI2 and TxA2 were the fingerprints for tracking their isolation and ultimate chemical identification. These studies were responsible for opening the modern era of vascular biology that has facilitated the development of a rational approach to the treatment of diabetic and hypertensive complications involving the arterial circulation. PMID- 17332672 TI - Up-regulation of vascular cyclooxygenase-2 in diabetes mellitus. AB - Diabetes mellitus is associated with disturbed regulation in the microcirculation. A low-grade vascular inflammation has been implicated in the development of diabetes-related vascular complications, but the underlying molecular mechanisms has not yet been fully elucidated. It is known that cyclooxygenase-2 (COX-2) plays a key role in prostaglandin biosynthesis during the development of inflammation. Recent studies revealed that in diabetes increased synthesis of various prostanoids, via up-regulation of COX-2, interferes with the regulation of vasomotor function. In this review, we will summarize the current findings regarding the role of COX-2, and COX-2-derived prostanoids in the regulation of vascular tone, as well as the possible underlying mechanisms leading to COX-2 activation in diabetes mellitus. PMID- 17332673 TI - Lipid peroxidation, isoprostanes and vascular damage. AB - Increased lipid peroxidation has been identified as a key mechanism for the development of atherosclerosis and inflammatory vascular damage. Determination of plasma concentration and urinary excretion of some F(2)-isoprostanes (by immunometric assays or by mass-spectrometry), has been demonstrated to be a reliable approach to the assessment of lipid peroxidation, and therefore of oxidative stress in vivo . Several lines of evidence suggest that isoprostane generation may reflect oxidative stress in experimental and human atherosclerosis. Increased lipid peroxidation may precede the development of atherosclerosis. In fact, urinary excretion or plasma levels of an abundantly generated F(2)-isoprostane, 8-iso-PGF(2alpha) have been found to be more elevated in subject with cardiovascular risk factors than in healthy subjects. Some isoprostanes, in particular 8-iso-PGF(2alpha) have been demonstrated to have biological activities that may contribute to the progression of vascular damage inducing endothelial and platelet activation and being powerful vasocostrictors. Increased lipid proxidation may be implicated in the bioactivity of angiotensin II. Experimental data indicate that increased oxidative stress due to activation of NAD(P)H oxidase is an obligatory step in its pro-hypertensive and pro atherosclerotic effects. Increased generation of F(2)-isoprostanes is observed in clinical and experimental conditions in which angiotensin II activity is increased. In conclusion, measurement of some F(2)-isoprostanes in biological liquids represents a reliable marker of oxidative stress in vivo. The potential contribution of these compounds to the pathophysiology of the vascular damage and atherosclerosis has not yet been defined. PMID- 17332674 TI - Endothelial dysfunction in pre-eclampsia. AB - The repeated demonstration of biomarkers of endothelial cell and leukocyte activation has suggested that the maternal syndrome of pre-eclampsia arises from a generalised maternal inflammatory systemic response incorporating a substantive component of endothelial cell dysfunction. Reports of reduced endothelium dependent dilatation in isolated resistance arteries and from non invasive methods in vivo indicate a major contribution to the systemic vasoconstriction, characteristic of the syndrome. The recent discovery of raised concentrations of soluble fms-like tyrosine kinase1(sFlt1) and the soluble transforming growth factor beta (TGF-beta) coreceptor (sEng) sEng which indirectly may compromise endothelial function, adds to the growing list of potential origins of endothelial disturbance. Most are proposed to originate from placental underperfusion and associated placental oxidative stress, although it is clear that not all women with pre-eclampsia have reduced utero-placental blood flow, and other precipitating factors, including dyslipidaemia and hyperglycaemia are likely to contribute. Endothelial dysfunction, unlike pre-eclampsia, does not resolve post-partum, and persistence of the defect may underpin the increased risk of cardiovascular disease in later life. PMID- 17332675 TI - Glycocalyx and endothelial (dys) function: from mice to men. AB - Located on the luminal surface of vascular endothelial cells, the glycocalyx is composed of a negatively charged mesh of proteoglycans, glycosaminoglycans, glycoproteins and glycolipids and harbors a wide array of enzymes that contribute in regulation of leukocyte-/thrombocyte adherence, with a principal role in plasma and vessel wall homeostasis. Glycocalyx disruption is accompanied by enhanced sensitivity of the vasculature towards atherogenic stimuli which emphasizes that not only the composition of the glycocalyx is important in facilitating these properties but that the contribution of its physical dimension and barrier properties should also be considered. In addition, similarities found between micro-versus macro vascular beds suggest common structural properties throughout the entire vascular bed that might be of importance in protective strategies against vascular perturbation. Collectively, these data lend support to a potential role of the glycocalyx as a first barrier in protection against atherogenic insults. Therefore, it will be a challenge to determine whether glycocalyx volume measurement, systemically or at the individual capillary level, is a feasible surrogate marker for cardiovascular disease, and whether it may prove to be of use to assess the impact of novel interventions aimed at glycocalyx restoration on atherosclerosis progression. PMID- 17332676 TI - Adipose tissue, inflammation and endothelial dysfunction. AB - During the last decade, white adipose tissue was recognized to be an active endocrine organ and a source of many proinflammatory cytokines, chemokines, growth factors and complement proteins. Many of these adipokines seem to play an important role in the pathogenesis of obesity-related diseases including accelerated atherosclerosis, arterial hypertension and some glomerulopathies. As endothelial dysfunction is one of the early stages of atherosclerosis, it is reasonable to consider that substances secreted by adipose tissue may influence directly or indirectly (for instance by induction of microinflammation) the function of endothelial cells. The aim of this review is to summarize the evidences and hypotheses concerning the role of adipokines in the pathogenesis of endothelial dysfunction. PMID- 17332677 TI - Endothelial mitochondria as a possible target for potassium channel modulators. AB - Variety of ion channels is present in plasma membrane of endothelial cells. These include the potassium channels such as Ca(2+)-activated K(+) channels, inwardly rectifying K(+) channels, voltage-dependent K(+) channels and also ATP-regulated K(+) channels. Due to an influence on the membrane potential they are important regulators of vascular tone by modulating endothelial calcium ions signaling and synthesis of vasodilating factors. Potassium channels in mitochondrial membranes of various tissues, similar to plasma membrane potassium channels, are described. Mitochondrial potassium channels such as ATP-regulated or large conductance Ca(2+)-activated and voltage gated channels are implicated in cytoprotective phenomenon in different tissues. In this paper we describe the pharmacological properties of mitochondrial potassium channels and discuss their role of as novel pharmacotherapeutic targets in endothelium. PMID- 17332678 TI - Arachidonate and NADPH oxidase synergise with iNOS to induce death in macrophages: mechanisms of inflammatory degeneration. AB - Inflammation contributes to many pathologies, but the mechanisms by which inflammation induces cell death are unclear. We investigated interactions between inducible nitric oxide synthase (iNOS), phagocytic NADPH oxidase (PHOX) and arachidonate in inducing cell death in a J774 macrophage cell line. Little or no cell death was induced by: (i) induction of iNOS with lipopolysaccharide (LPS) and interferon-gamma (INFgamma), (ii) activation of PHOX with phorbol-12 myristate-13-acetate (PMA), or (iii) addition of arachidonate. However, when iNOS activation was combined with PHOX activation by PMA or with arachidonate, there was extensive necrotic death of macrophages. In both cases death was accompanied by peroxynitrite production, and was blocked by removal of peroxynitrite (by FeTPPS), removal of superoxide (by superoxide dismutase), inhibition of iNOS (by 1400W) or inhibition of PARP (by IsoQ or DPQ). However, when iNOS induction was combined with PMA, death was blocked by a PHOX inhibitor (apocynin). Whereas when iNOS induction was combined with arachidonate, death was not blocked by apocynin, but was blocked by a cyclooxygenase (COX) inhibitor (ibuprofen), suggesting that the source of superoxide contributing to cell death differs in these two conditions. PMID- 17332679 TI - Nebivovol and carvedilol induce NO-dependent coronary vasodilatation that is unlikely to be mediated by extracellular ATP in the isolated guinea pig heart. AB - In contrast to classical beta-adrenoreceptor antagonists, nebivolol and carvedilol possess endothelium-dependent vasorelaxant properties. It has been proposed that nebivolol and carvedilol activate microvascular endothelium into producing NO by the release of extracellular ATP and subsequent stimulation of endothelial P(2) receptors. Here we tested this hypothesis in the coronary circulation of the isolated guinea pig heart. We analyzed the role of NO in the coronary vasodilatation induced by nebivolol and carvedilol as well as a possible involvement of extracellular ATP in these responses. Nebivolol and carvedilol (3 30 x 10(-6) M) induced a concentration-dependent coronary vasodilatation that was inhibited by NO-synthase inhibitor, L-NAME (10(-4) M). In contrast to nebivolol and carvedilol, neither atenolol nor labetalol acted as a coronary vasodilator. Vasodilatation induced by nebivolol and carvedilol was affected neither by the P(1) receptor antagonist, 8-sulfophenyl theophylline (8-SPT, 10(-5) M), nor by the P(2) receptor antagonist, suramin (10(-5) M). On the other hand, ATP-induced coronary vasodilatation (0.3-10 x 10(-6) M) was strongly inhibited by L-NAME (10( 4) M), partially inhibited by 8-SPT (10(-5) M), while suramin (10(-5) M) had a minor effect. In conclusion, in the isolated guinea pig heart nebivolol and carvedilol, but not their classical counterparts (atenolol, labelatol), act as NO dependent coronary vasodilators. It seems unlikely that this response is mediated by the release of extracellular ATP. PMID- 17332680 TI - X-linked inhibitor of apoptosis protein regulates human interleukin-6 in umbilical vein endothelial cells via stimulation of the nuclear factor-kappaB and MAP kinase signaling pathways. AB - X-linked inhibitior of apoptosis (XIAP) is known as a potent inhibitor of apoptosis, but more recently has been shown to also act as a modulator of the nuclear factor kB (NF-kappaB) signaling pathway. To investigate whether XIAP also affects other signalling pathways, we studied the transcriptional regulation of interleukin 6 (IL-6), a gene that is strongly affected by XIAP, in more detail. The human IL-6 gene contains transcription factor binding sites for activator protein 1 (AP1), enhancer binding protein beta (C/EBP-beta) and NF-kappaB. In reporter gene assays, mutation of these binding sites revealed the necessity of functional NF-kappaB and AP1-sites for its ability to respond to XIAP. In contrast, IL-6 promoter activity was slightly increased in the C/EBP deletion mutant. Pharmacologic inhibition of extracellular signal regulated kinase (ERK) kinases (MEK1/2) as well as inhibition of the p38 signaling pathway both reduced XIAP-induced IL-6 promoter activity. In conclusion, these results suggest that XIAP regulates IL-6 transcription via NF-kappaB in cooperation with AP1 and C/EBP beta. PMID- 17332681 TI - Species differences of endothelial extracellular nucleotide metabolism and its implications for xenotransplantation. AB - There is a severe shortage of human organs available for transplantation and xenotransplantation - use of animal organs has long been suggested to overcome this problem. Recent advances in understanding rejection in xenotranplantation and development of genetically engineered pigs that reduced hyperacute rejection were fundamental steps forward but other unresolved mechanisms remain an obstacle. Endothelium is a major target for all rejection mechanisms in xenotransplantation. This is caused not only by location of these cells at the first line of contact but also because endothelium is a very variable cell type across different species. This variability affects not only its immune characteristics but also physiology and metabolism. Nucleotide metabolism is particularly variable in endothelial cells of different species. We attributed particular importance to one such difference - much lower activity of ecto-5' nucleotidase (E5'N) in pig endothelial cells as compared to human. To study its significance our group developed pig endothelial cell line stably expressing human E5'N. This allowed us to determine that E5'N controls the rate of adenosine formation from extracellular nucleotides even with ATP as the substrate. Expression of human E5'N in pig cells attenuated several mechanisms involved in xenotransplant rejection such as cytotoxicity induced by human NK cells, human platelet aggregation or human platelet adherence to endothelium. We conclude that species differences of endothelial nucleotide metabolism could contribute to rejection following xenotransplantation. These studies suggests that expression of human ecto-5'-nucleotidase in pigs genetically engineered for xenotransplantation could help to prolong graft survival. PMID- 17332682 TI - Are the endothelial mechanisms of ACE-Is already established? AB - The endothelial mechanism of ACE-Is action is multifaceted. On the one hand, by inhibiting ACE, ACE-Is diminish Ang II synthesis, one of the best known active peptides. On the other hand, they modify synthesis and release of PGI(2) and NO via increasing production of other biologically important peptides like bradykinin, Ang-(1-7) or Ang-(1-9). Thus, ACE-Is play a crucial role in the function of endothelium and are effective and important tool for therapy of range of cardiovascular system disorders. Moreover, they are sensitive pharmacological instrument to elucidate and expand our knowledge about the role of RAS in human patophysiology. PMID- 17332683 TI - A carbon monoxide-releasing molecule (CORM-3) attenuates lipopolysaccharide- and interferon-gamma-induced inflammation in microglia. AB - The development of carbon monoxide-releasing molecules (CO-RMs) in recent years helped to shed more light on the diverse range of anti-inflammatory and cytoprotective activities of CO gas. In this study, we examined the effect of a ruthenium-based water-soluble CO carrier (CORM-3) on lipopolysaccharide (LPS)- and interferon-gamma (INF-gamma)-induced inflammatory responses in BV-2 microglial cells and explored the possible mechanisms of action. BV-2 microglial cells were stimulated with either LPS or INF-gamma in the presence of CORM-3 and the inflammatory response evaluated by assessing the effect on nitric oxide production (nitrite levels) and tumor necrosis factor-alpha (TNF-alpha) release. Similar experiments were also performed in the presence of inhibitors of guanylate cyclase (ODQ), NO synthase (L-NAME), heme oxygenase activity (tin protoporphyrin IX) or various mitogen-activated protein kinase (MAPK) inhibitors. CORM-3 significantly attenuated the inflammatory response to LPS and INF-gamma as evidenced by a significant reduction (p < 0.001) in nitrite levels and TNF-alpha production (P < 0.05). Such effect was maintained in the presence of ODQ, L-NAME or tin protoporphyrin without showing any cytotoxicity. The use of an inactive form of CORM-3 that does not contain carbonyl groups (Ru(DMSO)(4)Cl(2) failed to inhibit the increase in inflammatory markers suggesting that liberated CO mediates the observed effects. In addition, inhibition of phosphatidylinositol-3 phosphate kinase (PI3K) and extracellular signal-regulated kinase (ERK) pathways seemed to amplify the anti-inflammatory effect of CORM-3, particularly in cells stimulated with INF-gamma. These results suggest that the anti-inflammatory action of CORM-3 could be exploited to mitigate microglia activation in neuro inflammatory diseases. PMID- 17332684 TI - Nitric oxide in cardiac transplantation. AB - The endothelium of coronary arteries has been identified as an important organ locally regulating coronary perfusion and cardiac function by paracrine secretion of nitric oxide (NO) and other vasoactive mediators. Therefore, the established organ procurement in cardiac transplantation using hypothermic storage solutions designed to preserve myocytes but not endothelial cells has to be critically discussed. Heart transplantation is a prestigious high-end treatment for end stage heart failure patients with promising survival rates: 84% one-year and 65% five-year survival. However, these survival rates are still far from being satisfying requiring further research in organ preservation and perioperative management. This review will focus on possible strategies to improve donor and recipient management in regard to a functional endothelium and NO. The following topics will be addressed: (1) NO and ischemia/reperfusion, to understand the mechanisms that lead to NO depletion and its consequences. (2) NO and hypothermia, to understand the effects of hypothermia on the endothelium. (3) Current status of donor and recipient management, to describe the strategies used today. (4) Possible new approaches: NO-scavenging and NO-substitution, to describe the recent research that is performed in this area including some of our own results. (5) Outlook in donor and recipient management, to give possible new directions, deducted from our current knowledge. PMID- 17332685 TI - Pulmonary endothelium in the perinatal period. AB - The pulmonary circulation is the only system in the body which does not have a dress rehearsal in utero. The pulmonary endothelium plays a pivotal role in ensuring that the resistance falls rapidly after birth so that the lungs can receive and process the entire cardiac output for the first time. It transduces signals triggered by environmental changes to the underlying smooth muscle cells, controlling their reactivity and regulating pulmonary vascular tone. It also clears alveolar fluid. This review addresses the mechanisms involved in these processes and considers failure of adaptation, the syndrome of Persistent Pulmonary Hypertension. PMID- 17332686 TI - Measurement of plasma oxidized low-density lipoprotein and its clinical implications. AB - Oxidized low-density lipoprotein (OxLDL) has been shown to exist in human circulating plasma. Several groups including ours have developed methods for immunologically measuring OxLDL, which have been applied to several clinical, both cross-sectional and prospective, studies. These data clearly show that OxLDL levels correlate well with the severity of cardiovascular diseases. In particular, recent observations suggest that plasma OxLDL levels could be a useful marker for predicting future cardiovascular events; however, substantial differences exist among the different methods of OxLDL measurement. To evaluate the clinical data on circulating OxLDL, a proper understanding of the similarity, differences, and limitation of the methods is needed. This paper summarizes the characteristics of the methods used and recent clinical findings. PMID- 17332687 TI - Plasmalogens in human serum positively correlate with high- density lipoprotein and decrease with aging. AB - AIM: The objective of the present study was to propose plasmalogens as a beneficial factor in human plasma by showing a highly positive correlation with high-density lipoprotein (HDL) and a significant reduction with aging. METHODS: For 148 elderly subjects suspected of coronary artery disease (CAD), clinical characteristics such as coronary stenosis, hyperlipidemia, abnormal glucose tolerance, and hypertension were investigated, and serum biochemical markers including plasmalogens were determined. RESULTS: Serum plasmalogens levels tended to fall in significant coronary stenosis and abnormal glucose tolerance. Correlative analyses among serum biochemical markers revealed that plasmalogens positively correlate with HDL-related values, particularly apolipoprotein A-I (apo A-I), and that the molar ratio of choline plasmalogen (ChoPlas) to ethanolamine plasmalogen (EtnPlas) correlates positively with low-density lipoprotein (LDL) particle size, and negatively with apo A-II and fasting triglyceride (TG) levels. Comparison of plasmalogens in elderly subjects with those of 119 healthy young subjects showed a marked decrease in serum plasmalogens levels by aging. CONCLUSION: These results suggest that serum plasmalogens, antioxidant phospholipids, function as a beneficial factor as well as HDL, and that the measurement of serum plasmalogens is useful in clinical diagnosis. PMID- 17332688 TI - Association of genetic variation of the adiponectin gene with body fat distribution and carotid atherosclerosis in Japanese obese subjects. AB - AIM: The aim of this study was to investigate the effect of SNP45 of the adiponectin gene on body fat distribution and carotid atherosclerosis in Japanese obese subjects. METHODS: A total of 64 obese subjects were investigated. Genotypes of SNP45 were assayed by polymerase chain reaction-restriction fragment length polymorphism. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using computed tomography. The progression of atherosclerosis was evaluated by plaque score (PS) of carotid artery using B-mode ultrasonography. RESULTS: Men carrying the G allele of SNP45 showed higher VFA (172.8+/-50.8 vs. 147.1+/-58.7, p=0.005), lower SFA (209.9+/-101.8 vs. 273.4+/-142.2, p=0.007), higher VFA/SFA (V/S) ratio (1.00+/-0.46 vs. 0.60+/-0.26, p <0.001) and higher PS (9.5+/-3.7 vs. 6.8+/-4.2, p=0.012) than those with TT genotype. Multivariate analysis showed that SNP45 was an independent determinant of V/S ratio and PS in men. In subgroup analysis, PS tended to be associated with V/S ratio only in the carrier of 45G allele. CONCLUSION: These results suggest that the G allele could be a risk factor of metabolic syndrome and the development of atherosclerosis in Japanese obese subjects. PMID- 17332689 TI - Prevalence of metabolic syndrome in young men in Japan. AB - AIM: The prevalence of metabolic syndrome, as defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATPIII) modified for age (>or=3 of the following abnormalities): waist circumference of at least 80 cm; serum glucose level of at least 110 mg/dL; triglyceride level of at least 110 mg/dL; high density lipoprotein (HDL) cholesterol level of 40 mg/dL or less; and blood pressure (BP) of at least 130/75 mmHg, was estimated in male high school students who attended an annual school health examination. METHODS: The subjects were divided into three body mass index (BMI) categories (obese: >or=25; mildly obese: 23-24.9: and normal weight: <23 kg/m2). Of the 1446 students (mean age 15 years), 96 (6.6%) were obese and 158 (10.9%) were mildly obese. RESULTS: The overall prevalence of metabolic syndrome was 1.4%, being present in; 15.6% of obese subjects. Overall, elevated systolic BP was most common (19.9%). In obese subjects, 51% had an elevated systolic BP. CONCLUSION: Our study suggests that metabolic syndrome is present in more than 1% of male adolescents and 15% of obese male adolescents in Japan. PMID- 17332690 TI - Platelet aggregability in patients with hypertension treated with angiotensin II type 1 receptor blockers. AB - AIM: Cardiovascular events associated with hypertension often involve thrombosis. Increased platelet activity is one of the risk factors of cardiovascular diseases. Antithrombotic properties of antihypertensive agents are not fully characterized. Angiotensin II type 1 receptor blockers (ARBs) are widely used for the treatment of hypertension. Some ARBs can provoke antiaggregatory effects on platelets in vitro. Whether ARBs can inhibit platelet aggregation was tested in hypertensive patients in vivo. METHODS: Platelet aggregation was assessed by the highly sensitive particle counting method using laser-light scattering. RESULTS: Large platelet aggregation induced by adenosine diphosphate (ADP, 3 microM) was 2.6+/-0.4 (x10(7)) (SE) in hypertensive patients treated with losartan (72+/-3 years old, n=10) while it was 3.9+/-0.6 in hypertensive patients treated with candesartan (70+/-5 years old, n=6; p=0.056). Large platelet aggregation induced by thromboxane A2 receptor agonist, U46619 (10 microM), was 2.8+/-0.5 (x10(7)) in hypertensive patients treated with losartan while it was 5.1+/-0.9 in hypertensive patients treated with candesartan (p=0.033). Clinical characteristics including the control of blood pressure did not differ between the two groups (losartan 136+/-5/73+/-3 mmHg vs. candesartan 135+/-4/76+/-5). CONCLUSION: Thus, losartan may have the possibility to inhibit platelet activation in patients with hypertension independent of blood pressure reduction. Antiaggregatory properties may be independent of angiotensin II type 1 receptor or of antihypertensive actions. The favorable effects of losartan on reduction of adverse cardiovascular events among hypertensive patients may be at least partly mediated by inhibition of platelet activation. PMID- 17332691 TI - Metabolic syndrome may be a risk factor for early carotid atherosclerosis in women but not in men. AB - AIM: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities and a predictor of both type 2 diabetes mellitus and adverse cardiovascular events. Whether there are gender differences in the association between early atherosclerosis and MetS has not yet been thoroughly elucidated. METHODS: The subjects consisted of 388 men aged 64+/-16 years and 480 women aged 70+/-13 years. Early atherosclerosis was assessed by carotid intima-media thickness (IMT) on B-mode ultrasonography. RESULTS: Carotid IMT values were significantly greater in both male (p=0.007) and female (p=0.002) subjects with MetS. After adjusting for established risk factors, the difference persisted on a significant level in women (p=0.003), but was weak in men (p=0.013). Multiple regression analysis using IMT as an objective variable, with adjustment for various risk factors as explanatory variables, showed that MetS (p=0.016) was a significant independent contributing factor along with known risk factors only in women. Among the components of MetS, hypertension (p=0.036) and dyslipidemia (p=0.008) had a strong impact on carotid IMT in men, whereas hypertension (p=0.003) ranked first in women. CONCLUSION: The effect of MetS in early carotid atherosclerosis is more pronounced in women than in men, and the impact of MetS components on carotid IMT differs between men and women. PMID- 17332692 TI - Protective action of indapamide, a thiazide-like diuretic, on ischemia-induced injury and barrier dysfunction in mouse brain microvascular endothelial cells. AB - The aim of the present study was to elucidate the effects of indapamide on ischemic damage to the blood-brain barrier (BBB) in vitro. The ischemia/reperfusion conditions employed here significantly decreased the viability of mouse brain capillary endothelial (MBEC4) cells, an effect ameliorated by indapamide. Ischemia increased the permeability of MBEC4 cells to two cellular transport markers, sodium fluorescein and Evan's blue-albumin. Indapamide reduced the ischemia-induced hyperpermeability of cells. These results suggest that indapamide may have a protective role against ischemia-induced injury and dysfunction of the BBB. PMID- 17332693 TI - Mechanism of Na+/Ca2+ exchanger activation by hydrogen peroxide in guinea-pig ventricular myocytes. AB - Using the whole-cell voltage clamp, we examined the mechanism of activation of the Na(+)/Ca(2+) exchanger (NCX) by hydrogen peroxide (H(2)O(2)) in isolated guinea-pig cardiac ventricular myocytes. Exposure to H(2)O(2) increased the NCX current. The effect was inhibited by cariporide, an inhibitor of the Na(+)/H(+) exchanger (NHE), suggesting that there are NHE-dependent and -independent pathways in the effect of H(2)O(2) on NCX. In addition, both pathways were blocked by edaravone, a hydroxyl radical (*OH) scavenger; pertussis toxin, a Galpha(i/o) protein inhibitor; and U0126, an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK). On the other hand, wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, inhibited only the NHE-dependent pathway, while PP2, a Src family protein tyrosine kinase inhibitor, inhibited only the NHE-independent pathway. Taken together, our data suggest that H(2)O(2) increases the NCX current via two signal transduction pathways. The common pathway is the conversion of H(2)O(2) to *OH, which activates Galpha(i/o) protein and a mitogen-activated protein (MAP) kinase signaling pathway. Then, one pathway activates NHE with a PI3K-dependent mechanism and indirectly increases the NCX current. Another pathway involves activation of a Src family tyrosine kinase. PMID- 17332694 TI - Oxidants in the gas phase of cigarette smoke pass through the lung alveolar wall and raise systemic oxidative stress. AB - Cigarette smoking-induced oxidative stress plays a key role in the pathogenesis of atherosclerosis in smokers. Aqueous cigarette smoke extract (CSE) contains stable oxidants, peroxynitrite-like reactants, which have the ability to oxidize and nitrate low-density lipoprotein (LDL). We examined whether oxidants in CSE can penetrate into the blood through the lung alveolar wall and cause oxidative vascular injury. The oxidants in CSE and sodium peroxynitrite could easily pass through the reconstituted basement membrane. When CSE or sodium peroxynitrite solution was infused into the alveolar air space of an isolated rat lung mounted in tyrosine solution, CSE gradually increased the 3-nitrotyrosine levels in the external tyrosine solution while sodium peroxynitrite caused a rapid increase. CSE did not activate the rat alveolar macrophages. When rats were acutely exposed to the gas phase of cigarette smoke from which tar and nicotine had been removed, both serum levels of 3-nitrotyrosine and 8-hydroxy-2'-deoxyguanine, oxidative stress markers, rapidly increased. Our results demonstrate that relatively stable oxidants in CSE can pass through the pulmonary alveolar wall into the blood and induce systemic oxidative stress, which most likely facilitates oxidative modification of LDL and endothelial dysfunction, explaining early key events in the development of atherosclerosis. PMID- 17332695 TI - Analysis of uteroplacental-specific molecules and their functions during implantation and placentation in the bovine. AB - In cattle, the mechanisms underlying implantation and placental development are still unclear. Synepitheliochorial placentation in cattle is noninvasive, and thus generates limited interest in terms of degradation and remodeling of endometrial tissues. The overall purpose of this study was three-fold: (1) to examine the gene circuitry around the implantation window, (2) to understand development of the placenta during the peri-implantation period by using a uteroplacental cDNA microarray, and (3) to study the roles of molecules involved in endometrial remodeling. Bovine trophoblastic binucleate cell-specific molecules, such as pregnancy-associated glycoproteins (PAGs), placental lactogen (PL), and prolactin-related proteins (PRPs), were markedly expressed in binucleate cells (BNCs) around implantation. The expression of PRP-1 was specific to the caruncular (CAR) area of the gravid uterine horn. Gelatinases (MMP-2 and 9) in association with heparanase may be central to endometrial remodeling. In situ hybridization analyses of PAGs, PRPs, PL, and heparanase suggested that BNCs expressed these molecules simultaneously. Future studies will further investigate the specific roles of these molecules in placentogenesis. The uteroplacental cDNA microarray presented cascades of molecular signatures not only for the endometrium but also for the intricate dialogue at the level of the feto-maternal interface in cattle. Placentome morphogenesis potentially parallels the dynamic multigenic circuitry and regulates the cell cycle in the endometrium. The roles of BNCs and their secreted molecules remain an enigma, particularly with regard to the adhesion process and endometrial remodeling, which is the focus of this study. PMID- 17332696 TI - Production of cloned mice and ES cells from adult somatic cells by nuclear transfer: how to improve cloning efficiency? AB - Although it has now been 10 years since the first cloned mammals were generated from somatic cells using nuclear transfer (NT), most cloned embryos usually undergo developmental arrest prior to or soon after implantation, and the success rate for producing live offspring by cloning remains below 5%. The low success rate is believed to be associated with epigenetic errors, including abnormal DNA hypermethylation, but the mechanism of "reprogramming" is unclear. We have been able to develop a stable NT method in the mouse in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. Especially in the mouse, only a few laboratories can make clones from adult somatic cells, and cloned mice are never successfully produced from most mouse strains. However, this technique promises to be an important tool for future research in basic biology. For example, NT can be used to generate embryonic stem (NT-ES) cell lines from a patient's own somatic cells. We have shown that NT-ES cells are equivalent to ES cells derived from fertilized embryos and that they can be generated relatively easily from a variety of mouse genotypes and cell types of both sexes, even though it may be more difficult to generate clones directly. In general, NT-ES cell techniques are expected to be applied to regenerative medicine; however, this technique can also be applied to the preservation of genetic resources of mouse strain instead of embryos, oocytes and spermatozoa. This review describes how to improve cloning efficiency and NT-ES cell establishment and further applications. PMID- 17332697 TI - Sex preselection in bovine by separation of X- and Y-chromosome bearing spermatozoa. AB - Flow cytometrically-sorted sperm has been involved in the production of sex preselected offspring. More than 30,000 bovine offspring have been produced using AI and other means using spermatozoa separated by flow cytometer. Flow cytometric sperm sorting based on differences in their DNA content is the best method for separation of X- and Y-chromosome bearing spermatozoa. At first, flow cytometers were modified for DNA confirmation and sorting of sperm with high resolution. The beveled insertion needle can regulate orientation of flat-shaped bull sperm heads. The forward fluorescence detector is essential for measuring the DNA content of sperm. Recently, high-speed sperm sorting with orienting nozzles has resulted in production of 90% pure X- and Y-sperm at rate of 15-20 million sperm per hour. Application of this new technique will enable conduct of more conventional technologies for both artificial insemination and cryopreservation in the bovine and in other farm animals using X- or Y-sperm. PMID- 17332698 TI - Studies of follicular vascularity associated with follicle selection and ovulation in cattle. AB - We reviewed recent in vivo studies of the real-time changes in the vasculature of the follicle wall during selection of the dominant follicle as well as during ovulation in cows. Changes in follicle diameter and vascularity were determined by transrectal ultrasonography. Blood flow within the walls of the two largest follicles was detected at the time of wave emergence (largest follicle=5 mm in diameter). Before selection of a follicle (largest follicle <8.5 mm in diameter), the degrees of vascularity of the two largest follicles were not significantly different. After the largest follicle reached a diameter of 10 mm, the vascularity of the largest (dominant) follicle was higher than that of the second largest (subordinate) follicle. In the preovulatory follicle, follicular vascularity gradually increased, and as ovulation approached, the LH-surge induced an increase in blood flow within the follicle wall. The above results suggest that maintenance of follicular vasculature and appropriate blood supplies to follicles are essential for establishment of follicular dominance. Consequently, only a dominant follicle with high vascularity may have a chance to reach final maturation and acquire ovulatory capacity. PMID- 17332699 TI - [Two breakthroughs in CGD studies]. AB - Studies in Chronic Granulomatous Disease showed two breakthroughs during this past decade. First, the discovery of 7 Nox/Duox family proteins, Noxo1 and Noxa1 (homologues of gp91(phox), p47(phox) and p67(phox)) may clarify novel physiological mechanisms for superoxide regulation in various organs, such as the regulation of blood pressure, mucosal defense system in respiratory/digestive tract and nephron. Secondly, the success in bone marrow transplantation and gene therapy for CGD should facilitate treatment for other genetic diseases as well. PMID- 17332700 TI - [Heme oxygenase and its role in defense system; paradigm shift of anti inflammatory therapy]. AB - Heme oxygenase (HO) plays a central role in heme metabolism. At the same time, it protects cells from injury evoked by various oxidative stresses. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs. It is particularly important that in vivo HO-1 production is localized to selected cell types, e.g. renal tubular epithelium, reflecting the fact that HO-1 plays particularly important protective roles in these cells. In addition to renal epithelial cells and tissue macrophages, a minor subpopulation of circulating monocytes produced low, but significant levels of HO-1 and the number of these monocytes increased during episodes of acute inflammatory illnesses, indicating that monocytes play significant roles in controlling inflammation. On the other hand, excessive level of HO-1 induced by HO-1 gene transfection led to paradoxical susceptibility of the cells to oxidative injury. These results indicated that HO-1 expression is carefully controlled in vivo with regard to its location and the magnitude. Furthermore, it has been recently shown that HO-1 is involved in the immune regulation mediated by regulatory T cells. From these findings, it seems feasible to meticulously induce HO-1 protein in vivo as a novel therapeutic intervention to control various forms of inflammatory disorders. PMID- 17332701 TI - [Interplay between the immune and skeletal cells in the regulation of inflammatory bone destruction]. AB - The immune and skeletal systems share a number of regulatory molecules including cytokines, signaling molecules, transcription factors and membrane receptors, in common. Consequently, the physiology and pathology of one system may very well affect the other. Research into the cartilage and bone destruction associated with rheumatoid arthritis (RA) has highlighted the importance of the interplay between the immune and skeletal systems. This interdisciplinary field called osteoimmunology has attracted much attention in recent years. Recently, animal models deficient in immunomodulatory molecules have been found frequently to develop an unexpected skeletal phenotype. Receptor activator of NF-kappaB ligand (RANKL) is an essential factor for the induction of osteoclastogenesis that links the immune and skeletal systems. Thus, osteoimmunology is becoming increasingly important for understanding the pathogenesis of bone destruction in RA and for developing new therapeutic strategies for diseases affecting both systems. Here we summarize recent advances on the study of the regulation of cartilage and bone destruction by the immune system. PMID- 17332702 TI - [Abnormalities in lymphocyte telomerase activity and telomere length in systemic lupus erythematosus]. AB - T-cell telomerase activity was high in the active and inactive stages of systemic lupus erythematosus (SLE). In contrast, B-cell telomerase activity was very high only in the active stage. Compared with normal subjects, SLE patients had a shorter T-cell telomere, but their B-cell telomere length did not differ from that of normal subjects. These findings suggest that T cells are always activated, and that the manifestation of the disease requires the activation of not only T but also B cells. B-cell inhibition alone may be sufficient to suppress the clinical symptoms of SLE, but we consider that the essential treatment of SLE should target T cells as well. In recent years, various biologicals have begun to be used for the treatment of SLE. It is interesting how the use of such biologicals in the future will change T- and B-cell telomerase activity. In formulating a therapeutic strategy using biologicals for SLE, the measurement of telomerase activity in T and B cells seems useful for the preparation of target cells, selection of therapeutic drugs, and evaluation of therapeutic responses. PMID- 17332703 TI - [Classification of early arthritis patients and how to determine disease severity]. AB - Recent clinical studies of rheumatoid arthritis reveal that therapeutic intervention early in rheumatoid arthritis leads to less joint damage, indicating the importance of early diagnosis of RA for improvement of prognosis. According to the data of our "Early Arthritis Prospective Cohort", we have found that early arthritis patients, described as undifferentiated arthritis, progress to rheumatoid arthritis at high frequency if the patients positive with anti-cyclic citrullinated peptide antibody (anti-CCP antibody) and bone marrow edema at the entry. In addition, we are going to classify the pathologic status (disease severity) of early arthritis patients by serologic variables, radiographic findings and genetic analysis. PMID- 17332704 TI - [Evidence of cartilaginous benefit of treatment with infliximab in rheumatoid arthritis using measurement of serum COMP]. AB - Recently, it has become possible to measure the concentration of serum cartilage oligomeric matrix protein (COMP) in various arthritis, and it is expected to be a novel biomarker indicative of cartilage destruction. In this study, we evaluated the diagnostic effectiveness of serum COMP in rheumatic diseases and analyzed the inhibition of cartilage destruction in patients with rheumatoid arthritis who were prescribed with infliximab (IFX) for one year. The changes in the concentration of serum COMP and the joint narrow space of Sharp score (Delta Sharp-JNS) were evaluated. The level of serum COMP decreased from 23.04+/-7.14 U/l to 8.69+/-2.89 U/l (p<0.005) and improved Delta Sharp-JNS (-0.50+/-6.38 points). We believed that these results were influenced by the effects of methotrexate (MTX) that was prescribed together with IFX, and we analyzed the group that was administered only MTX therapy as a reference. However, the serum COMP concentration and Sharp-JNS in the MTX group did not decrease. The serological and radiological results revealed that IFX inhibited cartilage destruction, and it is possible that serum COMP is one of the novel biomarkers in RA patients treated with anti-tumor necrosis factor-alpha antibody therapy. PMID- 17332705 TI - [A case of lupus erythematosus profundus followed by systemic lupus erythematosus presenting with severe intestinal involvement]. AB - A 52-year-old female visited the outpatient department of Sapporo Medical University hospital in 1984 due to a refractory rash on the skin of the trunk. Histological findings of a skin biopsy specimen indicated a diagnosis of lupus erythematosus profundus (LEP). The eruption remained quiescent with moderate doses of prednisolone. In October 2003, she was suddenly admitted to our hospital with abdominal pain, fever and bloody stool. Lupus enteritis was diagnosed based on an elevated level of anti-DNA antibody, low complementemia and diffuse edematous change of the intestinal walls on CT scans. Although high doses of corticosteroids resulted in transient improvement, melena developed again on the 24th hospital day. Colonoscopy revealed deep ulceration at the rectum and a gastrografin enema indicated perforation. Accordingly, the involved rectum was resected and an artificial anus was constructed on the 50th hospital day. Examination of the resected specimen by microscopy showed that the ulceration approached at the depth of the subserosal layer with intense infiltration of inflammatory cells around the vessels. The pathogenesis of the rectal lesion might have been due to vasculitis associated with systemic lupus erythematosus (SLE). The disease did not recur under the administration of 10 mg of prednisolone daily until November 2004. Colonic function made a remarkably untroubled recovery after the artificial anus was closed in February 2005. The LEP was generally accompanied by a mild form of SLE. This case seemed to be rare in that SLE was associated with severe lupus enteritis and a refractory rectal ulcer developed from LEP. Patients with SLE and intestinal involvement should be carefully monitored in cooperation with a surgeon. PMID- 17332706 TI - [A case report of hypertrophic pachymeningitis associated with systemic lupus erythematosus, showing a headache and hearing loss resembling intracranial hypotension]. AB - We report a case of systemic lupus erythematosus (SLE) complicated with hypertrophic pachymeningitis. A 34-year old woman who was diagnosed as SLE in 1985 was admitted to our hospital for a high grade fever and a headache. Laboratory findings showed increased titer of anti-double strand DNA antibody and decreased number of platelets. She complained a severe headache and hearing loss which were worsened by head-up position, resembling the symptoms of intracranial hypotension. MRI findings revealed thickened dura and she was diagnosed as hypertrophic pachymeningitis. Both clinical symptoms and laboratory findings were resolved after methyl-prednisolone pulse therapy followed by a high dose of prednisolone. Although hypertrophic pachymeningitis is a rare complication with SLE, it should be considered in SLE patients with severe headache. PMID- 17332707 TI - Clinical usefulness of diffusion-weighted imaging using low and high b-values to detect rectal cancer. AB - PURPOSE: The purpose of this study was to assess the potential role of diffusion weighted imaging (DWI) using low and high b-values to detect rectal cancer. METHODS: The subjects were 15 patients diagnosed endoscopically with rectal cancer (m in 1 patient, sm in 0, mp in 3, ss in 7, se in 1, a in 3) and 20 patients diagnosed endoscopically with colon cancer and no other lesions (control group). Magnetic resonance imaging was performed using a 1.5T system. DWI was performed in the axial plane using echo planar imaging sequence (repetition time/echo time 1200/66, field of view 306x350 mm, reconstruction matrix 156x256, pixel size 2.0x1.4x8.0 mm) and acquired with 2 b-values (50 and 800 s/mm2). Low and high b-value DW images were analyzed visually. A lesion was positive by detection of a focal area of high signal in the rectum in high b-value images. The apparent diffusion coefficient (ADC) values of areas of high signal in high b value images were calculated from the low and high b-value images. RESULTS: High b-value images enabled visualization of all 15 rectal cancers. In the control group, 13 cases were classified as negative and 7 cases as positive for rectal cancer. Sensitivity for detection of rectal cancer was 100% (15/15), and specificity was 65% (13/20). The mean ADC values in 7 patients with false positive lesions and in 15 patients with rectal cancer were 1.374x10(-3) mm2/s (standard deviation [SD]: 0.157) and 1.194x10(-3) mm2/s (SD: 0.152), respectively (P=0.026). CONCLUSION: DWI with low and high b-values may be used to screen for rectal cancer. PMID- 17332708 TI - q-Space imaging using small magnetic field gradient. AB - q-Space diffusion analysis is a method to obtain the probability density function of the translational displacement of diffusing water molecules. Several quantities can be extracted from the function that indicate a characteristic of the water diffusion in tissue, e.g., the mean displacement of the diffusion, probability for zero displacement, and kurtosis of the function. These quantities are expected to give information about the microstructure of tissues in addition to that obtained from the apparent diffusion coefficient (ADC); however, this method requires high q (i.e., high b) values, which are undesirable in practical applications of the method using clinical magnetic resonance (MR) imaging equipment. We propose a method to obtain certain quantities that indicate a characteristic of the diffusion and that uses low q-value measurements. The quantities we can obtain are the moments of translational displacement, R; the n th order moment is defined as the average of Rn (n: integer). Kurtosis can also be calculated from the second and fourth moments. We tried to map the moments and kurtosis using clinical MR imaging equipment. We also estimated the inherent errors of the moments obtained. Our method requires precision in measuring spin echo signals and setting q values rather than using high q-value measurements. Although our results show that further error reductions are desired, our method is workable using ordinary clinical MR imaging equipment. PMID- 17332709 TI - Superparamagnetic iron oxide (SPIO) MRI contrast agent for bone marrow imaging: differentiating bone metastasis and osteomyelitis. AB - PURPOSE: We explored appropriate scan timing for bone marrow imaging enhanced using superparamagnetic iron oxide (SPIO) and evaluated the usefulness of SPIO in differentiating metastasis and osteomyelitis in patients. METHODS: To determine the adequate scan timing after administration of SPIO, 5 healthy subjects were examined using a 1.5T magnetic resonance (MR) imaging scanner. Sagittal images of their lumbar spines were obtained using short-TI inversion recovery (STIR) sequence before and 3, 6, 9, 24, and 48 hours after intravenous injection of 8 micromol Fe/kg SPIO (ferucarbotran). MR signal intensities (SIs) were evaluated. Based on the results, 12 patients, five with bone metastasis and seven with vertebral osteomyelitis, were examined using the same procedure before and 3 hours after intravenous injection of ferucarbotran at the same dose. SIs of the bone metastases, osteomyelitis, and surrounding normal bone marrow were measured, and relative enhancement (RE) was calculated for each lesion. RESULTS: In the healthy volunteers, maximum reduction in signal was observed 3 to 24 hours (P<0.05) after administration of SPIO; thereafter and up to 48 hours, the SI gradually recovered. In the patients, the RE of the bone metastases was -12.2%, which was significantly higher than that in the osteomyelitis (-35.0%, P<0.001) and normal bone marrow (-46.6%, P<0.0005). CONCLUSION: Maximum suppression of signal intensity in bone marrow was seen 3 hours after injection of ferucarbotran, the point at which ferucarbotran allows differentiation of bone metastasis from ostoemyelitis. PMID- 17332710 TI - Age-related changes in locus ceruleus on neuromelanin magnetic resonance imaging at 3 Tesla. AB - PURPOSE: To investigate age-related changes in the locus ceruleus (LC) in healthy subjects using neuromelanin magnetic resonance (MR) imaging at 3 Tesla. METHODS: We examined 64 healthy volunteers (aged 23 to 80 years) using neuromelanin sensitive T1-weighted images and measured the contrast of areas of high signal intensity corresponding to the LC. RESULTS: A pair of punctate areas of high signal intensity that represented neuromelanin within the noradrenergic neurons of the LC was easily recognized in all subjects. The contrast ratio of the LC to the adjacent pontine tegmentum increased to the age of 40 to 59 years and gradually and significantly decreased in elderly subjects. This correlates well with pathologically proven age-related changes in neuromelanin content within the LC. CONCLUSION: Age-related variance should be considered when determining the existence of abnormalities in the LC. PMID- 17332711 TI - Isotropic diffusion-weighted MR imaging with tetrahedral gradients in the upper abdomen. AB - A tetrahedral gradient diffusion sequence for body imaging for a 1.5T scanner was implemented, and we compared the quality of images acquired with the new technique and with the conventional orthogonal technique. Image quality was better using the tetrahedral technique in terms of signal homogeneity in the right liver lobe and signal loss artifact in the left lobe, and the technique was considered useful for magnetic resonance imaging in the upper abdomen. PMID- 17332712 TI - MR measurement of visceral fat: assessment of metabolic syndrome. AB - One diagnostic criterion for metabolic syndrome is obesity from the accumulation of visceral fat; others include abdominal circumference and area of visceral fat as measured by computed tomography (CT) at the umbilical level. We evaluated visceral fat using frequency-selective excitation magnetic resonance (MR) imaging SPAIR (spectral attenuation with inversion recovery) water suppression THRIVE (3D T1-high resolution isotropic volume examination). Fifty of 70 slices with 2-mm interval were used to render and measure volume of visceral fat ranging within 10 cm of the umbilicus; the area of visceral fat at the umbilical level was also measured. Imaging was completed using breath hold within 14 s. Image processing was easier than using CT. PMID- 17332713 TI - Transient splenial lesion of the corpus callosum after acute withdrawal of antiepileptic drug: a case report. AB - Transient lesions at the splenium of the corpus callosum (SCC) have been reported after withdrawal of specific antiepileptic drugs (AED), though the pathophysiology of the lesions remains unclear. We examined and treated a schizophrenic patient who developed a transient SCC lesion after withdrawal of the AED, carbamazepine. Interestingly, the SCC lesion was accompanied by the onset of diabetes insipidus, a state of arginine-vasopressin (AVP) insufficiency. Because carbamazepine is shown to potentiate the effect of AVP, our case suggests that an insufficiency of AVP followed by withdrawal of AED could contribute to the pathogenesis of a transient SCC lesion. PMID- 17332714 TI - Reducing fracture risk in the oldest old: aging and the effect of pharmaceutical interventions in osteoporosis. PMID- 17332715 TI - Collagen type 1 (COL1A1) Sp1 binding site polymorphism is associated with osteoporotic fractures but not with bone density in post-menopausal women from the Canary Islands: a preliminary study. AB - BACKGROUND AND AIMS: An association between the polymorphism for transcription factor Sp1 in the gene COL1A1 and low bone density (BMD) and osteoporotic fractures has been described but not confirmed for all races and ages. The aim of this preliminary work was to ascertain whether this association is present in women from the Canary Islands. METHODS: Polymerase chain reaction RFLP was used to determine COL1A1 polymorphism Sp1 in 199 consecutive outpatient post menopausal Caucasian women from the Canary Islands, aged 50-70 years. BMD was measured at lumbar spine and hip by DXA and at third lumbar vertebrae by QCT. Prevalent vertebral fractures were recorded on standard lateral X-ray film. Non vertebral osteoporotic fractures were registered by medical record and self reported history. Biochemical markers (serum osteocalcin, tartrate-resistant acid phosphatase), blood calcium and phosphate were also assessed. RESULTS: Distribution genotypes were 113 (50.8%) GG homozygotes, 73 (36.7%) Ss heterozygotes and 7 (3.5%) TT homozygotes. All patients with osteoporotic fractures carried the GG allele more frequently than TT homozygotic women. The odds ratio was 3.01 (95% CI 1.6-5.7) for prevalent vertebral fractures (n=62) and 2.33 (95% CI 1.2-4.4) for all osteoporotic fractures (n=65) for the T-carrying allele vs TT homozygotic women. There was no difference in BMD measured by DXA or QCT, nor in bone markers, blood calcium or phosphate. CONCLUSIONS: This preliminary study confirmed that the presence of at least one copy of the T allele is associated with osteoporotic fractures, but not with low BMD, in women from the Canary Islands. PMID- 17332716 TI - Life-quality indicators in elderly people are influenced by selenium status. AB - BACKGROUND AND AIMS: Selenium is of fundamental importance to human health. Our aim was to evaluate the effect of selenium (intake and serum levels) on subjective indicators of quality of life in older people, such as self-perceived health, chewing ability and physical activity. METHODS: The sample was a cohort of 227 elderly people (93 men and 134 women) residing in 14 nursing homes in Asturias (Spain). Mean age +/- SD was 72.9+/-7.2 y and 76.4+/-5.9 y, for men and women respectively. Information was collected in personal interviews. Dietary intake was recorded by means of a food-frequency questionnaire. Selenium was determined in serum by graphite-furnace atomic absorption spectrometry. RESULTS: Serum selenium was associated with self-perceived health, chewing ability and physical activity in this sample. Subjects in the upper tertile of serum selenium had more than twice as much probability (Odds Ratios, 2.05 to 3.157) of reporting good health status, good chewing ability and of doing more than 60 min of exercise/day. CONCLUSIONS: The maintenance of good serum selenium levels is important, since it may affect the self-perception of health, chewing ability, or physical activity and, consequently, the quality of life in elderly people. PMID- 17332717 TI - Factors underlying tiredness in older adults. AB - BACKGROUND AND AIMS: The purpose of the present study was to examine for factors related to tiredness, cross-sectionally at the age of 75 years, and factors related to subsequent onset of tiredness, from age 75 to 80 in a non-disabled community-living population. METHODS: The study is part of the prospective Nordic Research on Aging Study (NORA) on the 1914 cohort in Jyvaskyla, Finland and Glostrup, Denmark. In total, 546 non-disabled older men and women participated in the cross-sectional study at age 75, and 299 persons without tiredness and disability at baseline took part in the follow-up study, from age 75 to 80. Tiredness was measured by a validated scale based on the following items: using the toilet, washing and dressing lower body, and cutting toenails. Independent variables were: social position measured by housing tenure and income, chronic diseases, use of medicine, pain, muscle strength, lung function, cognitive performance, depressive symptoms, life satisfaction and insomnia. RESULTS: Analyses of cross-sectional data showed that social position, number of comorbidities, muscle impairment, pain and depressive mood were independently associated with tiredness. Longitudinal analyses showed that onset of tiredness was significantly or marginally significantly influenced by use of more than three drugs, muscle impairment, pain and cognitive impairment. CONCLUSIONS: The present study showed that tiredness in non-disabled older adults is a result of multiple potentially modifiable factors, which may be fully treated or at least alleviated, thus increasing the well-being of the individual, as well as potentially slowing the progression of disability. PMID- 17332718 TI - Starting artificial nutrition and hydration in patients with dementia in The Netherlands: frequencies, patient characteristics and decision-making process. AB - BACKGROUND AND AIMS: In many patients with dementia, the oral intake of fluids and nutrients becomes insufficient and a decision has to be made whether to start artificial nutrition or hydration (ANH). This study examines the incidence of ANH in nursing-home patients with dementia in The Netherlands, the methods of administration used, patient characteristics, and the characteristics of the ANH decision- making process. METHODS: In June 2001, a postal questionnaire was sent to all nursing-home physicians (NHPs) (n=1054) in The Netherlands. The response rate was 77%. RESULTS: Of the NHPs, 39% had started ANH during the 1-year study period, mostly by hypodermoclysis. As calculated from the total number of patients in The Netherlands, the incidence density for ANH in demented nursing home patients was 3.4 per 100 patient-years. The most important considerations in taking this decision were the patient's physical condition, the expected result of rehydration, and the (presumed) wishes of the patient. Decisions to start hydration resembled decisions to start nutrition, but more frequently concerned incompetent patients with an intercurrent infectious disease. CONCLUSIONS: Compared with the USA literature, ANH is practised less in The Netherlands. This practice conforms to the prevailing treatment policy endorsed by the Dutch Association of Nursing-Home Physicians. In starting nutrition and/or hydration, an agreement about the (limited) duration of ANH is generally made, and the NHPs generally involve relatives and nurses in the decision-making process. Almost always, all parties involved agreed with decisions taken. PMID- 17332719 TI - Clinically non-functioning pituitary macroadenomas in the elderly. AB - BACKGROUND AND AIMS: The aim of the present study was to evaluate the clinical presentation, characteristics and post-surgical outcome of non-functioning pituitary macroadenomas (NFPM) in elderly patients. METHODS: 27 patients (65-81 years; 13 Males, 14 Females) with NFPM (20-45 mm in diameter) were studied. The symptoms prompting neuroradiological studies were vision alterations in 52%, and dizziness, loss of memory, confusion, headache and depression in 29%; in 19% of patients, the disease was incidentally discovered during computed tomography (CT) or magnetic resonance imaging (MRI) for head trauma or cerebral ischemic attacks. RESULTS: Endocrinological evaluation on diagnosis showed global anterior hypopituitarism in 33% and partial hypopituitarism in 37% of patients. Immunohistochemistry showed signs of neurosecretion in most NFPM (chromogranin-A in 55%, gonadotropins in 19%, ACTH in 3.7%). Ki-67 antigen expression was indicative of low proliferative activity. Surgery was highly effective in improving alterations in vision and compressive symptoms, but was unable to restore normal pituitary function in established hypopituitarism in most cases. Eight patients (31%) were free of disease on subsequent MRI (follow-up 1-6 years). In 18 (69%) patients, a post-surgical residue was present. Of these, 6 (33%) underwent radiotherapy in the following years, owing to an increase in the volume of the remnants, and six (33%) underwent additional surgical treatment, followed by radiotherapy for further signs of growth in two. In the remaining patients, a small intrasellar remnant was stable on yearly MRI. CONCLUSIONS: in elderly patients, the development of hypopituitarism is often overlooked and the initial diagnosis of NFPM may be delayed. This can expose patients to the risks of unrecognized hypopituitarism and jeopardize post-surgical outcome. PMID- 17332720 TI - Low systolic blood pressure is associated with impaired cognitive function in the oldest old: longitudinal observations in a population-based sample 80 years and older. AB - BACKGROUND AND AIMS: The primary aim of the present study was to examine whether there is an association between blood pressure and the risk of subsequent cognitive decline in the oldest old. Various factors associated with blood pressure and cognitive function were considered. METHODS: The study comprised 599 individuals of a population-based sample, 199 men (mean age at baseline 82.8 years, range 80-95) and 400 women (mean age at baseline 83.3 years, range 80 100). Cognitive function was evaluated by the Mini Mental State Examination (MMSE). For a subgroup of 385 subjects (130 men, 255 women), data were available on blood pressure and MMSE at baseline and two followups at two-year intervals. Baseline blood pressure was studied in one group with reduced cognition and in another group with intact cognition across the following four years. The association of systolic blood pressure (SBP) with the MMSE score through the follow-up period was analysed controlling for frailty (time to death), age, gender, apoprotein E, homocysteine, hypertension, congestive heart failure, and stroke. RESULTS: A medical history of arterial hypertension was associated with lower MMSE scores and a higher prevalence of dementia and cognitive decline at baseline. However, intact cognition through the observation period was associated with higher baseline SBP. This relationship also remained when the frailty of aging subjects, indicated by remaining time to death, was taken into account. CONCLUSIONS: Lower SBP in the oldest old is associated with an increased risk of cognitive impairment even after adjustment for compromised vitality. In late life, the risk of cognitive decline needs to be considered in clinical practice. PMID- 17332721 TI - Twitch contractile properties of plantarflexor muscles in young and middle-aged recreationally physically active and non-active women. AB - BACKGROUND AND AIMS: This study examined the effect of recreational physical activity on the contractile properties of skeletal muscles in middle-aged vs young women. METHODS: A total 74 young (20-29-year-old) and middle-aged (45-54 year-old) women participated. The subjects were distributed into four groups: 1) young recreationally physically active (RPA) (n=19), 2) young recreationally physically non-active (RPN) (n=21), 3) middle-aged RPA (n=23) and 4) middle- aged RPN (n=16). RPA women exercised regularly in groups of recreational gymnastics 2 3 times per week. Isometric twitch of the plantarflexor muscles was evoked by supramaximal electrical stimulation of the tibial nerve in resting and post activation potentiation state. RESULTS: A greater resting twitch maximal rate of force development (RFD), and potentiated twitch peak force (PF) and maximal rate of relaxation (RR) were observed in the young RPA women compared with the two middle-aged women groups. In young RPN women, these characteristics were greater than in the middle-aged RPN women, whereas they did not differ significantly when compared with the middle-aged RPA women. A shorter resting and potentiated twitch contraction time, and a greater potentiated twitch maximal RFD were found in the young compared with the middle-aged groups. There were no significant differences in twitch characteristics between RPA and RPN women of similar age. CONCLUSIONS: The recreational gymnastic type of physical activity did not have a marked effect on twitch contractile properties in young and middle-aged women. A reduced speed of isometric twitch contraction was found in middle-aged women, which was more pronounced in the post-activation potentiation state. PMID- 17332722 TI - Prevalence and impact of osteoarthritis and osteoporosis on health-related quality of life among active subjects. AB - BACKGROUND AND AIMS: To assess the prevalence and impact of osteoarthritis (OA) and osteoporosis (OP) on health-related quality of life (HRQOL) among active subjects employed in the public workforce in Belgium. METHODS: A cohort of 3440 subjects employed by the Liege City Council was prospectively followed for 6 months. The employees were asked to fill in a monthly log in a health record book, of data regarding their healthcare consumption due to OA and OP. HRQOL was assessed using the Medical Outcomes Study Short Form-36 (SF-36). RESULTS: 1811 subjects (52.6%) filled in at least one questionnaire. The mean duration of follow-up was 3.46 months. The self-reported prevalence of OA and OP at entry to the study were respectively 34.1% and 5.3%. 3.6% of subjects reported suffering from both OA and OP. Subjects with OA and both OA and OP had significantly lower scores on all SF-36 dimensions compared with normal subjects, reflecting a worse HRQOL. The OP group had significantly lower mean scores for physical functioning and pain compared with controls. Subjects with both OA and OP had significantly lower values for physical functioning, physical role and pain when compared with the OA and OP groups. CONCLUSIONS: The results of this survey of a large sample of active subjects show that self-reported osteoarthritis and osteoporosis are common in the workplace. Both diseases have a major impact on health-related quality of life compared with that of people without self-reported musculoskeletal diseases. PMID- 17332723 TI - Self-maintenance Habits and Preferences in Elderly (SHAPE): reliability of reports of self-care preferences in older persons. AB - BACKGROUND AND AIMS: Self-care preferences can be used in designing programs of care. Yet little has been documented concerning the self-care habits and preferences of older adults. METHODS: This study assessed the reliability of reports of self-care preferences and their importance among older adults using the Self-maintenance Habits and Preferences in Elderly (SHAPE) instrument. Twenty community-dwelling seniors completed the SHAPE questionnaire twice within a one- to two-week interval. Percent agreement, both exact and close/partial, was computed to assess the reliability of preference content, and intra-class correlations (ICCs) were used for preference importance. Test and subject factors affecting reliability were also investigated. RESULTS: Exact agreement rate for item content was 73%, and that for close/partial agreement was 93%. Mean ICC for item importance was 0.72. Reliability was greater for dichotomous items than for either ordinal or categorical questions. Reliability of item content varied with number of response options and importance reliability varied with age and IADL status. CONCLUSIONS: Information from SHAPE about self-care preferences can be used to plan services for seniors and to individualize care for older persons, especially those transitioning to new living environments or those receiving home care. PMID- 17332724 TI - Hospital survival of older patients admitted to a medical intensive care unit. AB - BACKGROUND AND AIMS: It is not well-known whether age or the severity of underlying conditions affects mortality in critically ill patients. The aim of this study was therefore to determine whether age is an independent predictor of hospital survival for critically ill patients. METHODS: Patients consecutively admitted to the intensive care unit from December 1 1999 to July 31 2001 were included in the study. Patients were stratified into 3 groups (< or = 65 years old, 66-75 years old, > 75 years old) and were compared, by both bivariate and multivariate analyses, to ascertain whether older critically ill patients had poorer hospital survival than younger patients. RESULTS: Of 331 patients, 178 (53.8%) patients were < or = 65 years old, 100 (30.2%) were 66-75 years old, and 53 (16%) were > 75 years old. Multivariate logistic regression analysis revealed that older age, presence of fatal comorbidities, mechanical ventilation, central venous catheterization, and higher acute physiology and chronic health evaluation score II (excluding the score obtained from age) were independent predictors of hospital mortality in the study population. Kaplan-Meier survival analysis revealed that patients < or = 65 years old had better hospital survival than older patients (p=0.02). CONCLUSIONS: Older critically ill patients have poorer hospital survival than patients < or = 65 years old, when other confounding factors such as disease severity score, invasive procedures and comorbidities were controlled for. PMID- 17332725 TI - Unhealthy lifestyles during the life course: association with physical decline in late life. AB - BACKGROUND AND AIMS: This study aimed at examining the association between unhealthy lifestyle in young age, midlife and/or old age and physical decline in old age, and between chronic exposure to an unhealthy lifestyle throughout life and physical decline in old age. METHODS: The study sample included 1297 respondents of the Longitudinal Aging Study Amsterdam (LASA). Lifestyle in old age (55-85 y) was assessed at baseline, whereas lifestyle in young age (around 25 y) and midlife (around 40 y) were assessed retrospectively. Lifestyle factors included physical activity, body mass index (BMI), number of alcohol drinks per week and smoking. Physical decline was calculated as a change in physical performance score between baseline and six-year followup. RESULTS: Of the lifestyle factors present in old age, a BMI of 25-29 vs BMI < 25 kg/m2 (OR=1.6; 95% CI: 1.1-2.2) and a BMI of > or = 30 vs BMI < 25 kg/m2 (OR=1.8; 95% CI: 1.2 2.7) were associated with physical decline in old age. Being physically inactive in old age was not significantly associated with an increased risk of physical decline, although, being physically inactive in both midlife and old age increased the odds of physical decline in old age to 1.6 (95% CI: 1.1-2.4), compared with respondents who were physically inactive in midlife and physically active in old age. Being overweight in both age periods was associated with an OR of 1.5 (95% CI: 1.1-2.2). CONCLUSIONS: These data suggest that overweight in old age, and chronic exposure to physical inactivity or overweight throughout life, increases the risk of physical decline in old age. Therefore, physical activity and prevention of excessive weight at all ages should be stimulated, to prevent physical decline in old age. PMID- 17332726 TI - Prevalence of chronic kidney disease and associated risk factors--United States, 1999-2004. AB - Chronic kidney disease (CKD) is a serious condition associated with premature mortality, decreased quality of life, and increased health-care expenditures. Untreated CKD can result in end-stage renal disease and necessitate dialysis or kidney transplantation. Risk factors for CKD include cardiovascular disease, diabetes, hypertension, and obesity. To estimate the prevalence of CKD in the United States (overall and by health risk factors and other characteristics), CDC analyzed the most recent data from the National Health and Nutrition Examination Survey (NHANES). This report summarizes the results of that analysis, which determined that 16.8% of the U.S. population aged >/=20 years had CKD, according to 1999-2004 NHANES data, compared with 14.5% from the 1988-1994 NHANES (i.e., NHANES III), an increase of 15.9% based on crude estimates of prevalence. Persons with diabetes or cardiovascular disease had a greater prevalence of CKD than persons without those conditions. The results underscore the need to continue surveillance for CKD and its risk factors in the United States and to implement new strategies to reduce the number of persons with this condition. PMID- 17332727 TI - Escherichia coli O157:H7 infection associated with drinking raw milk--Washington and Oregon, November-December 2005. AB - During the week of December 5, 2005, public health officials in Clark County, Washington, were notified of four county residents with laboratory-confirmed Escherichia coli O157:H7 infection. All four residents reported having consumed raw (i.e., unpasteurized) milk obtained from a farm in neighboring Cowlitz County, Washington. The farm participated in a cow-share program, in which persons purchase interests in, or shares of, dairy cows in return for a portion of the milk produced. The farm had five dairy cows and regularly provided raw milk to shareholders. Although the sale of raw milk and cow-share agreements are illegal in certain states, they are legal in Washington; however, Washington farms that provide raw milk to consumers must be licensed, meet state milk production and processing standards, and pass health and sanitation inspections by the state department of agriculture. The Cowlitz County farm was not licensed. This report summarizes the investigation of E. coli O157:H7 cases associated with the farm and reinforces previous warnings about the health hazards of consuming raw milk. PMID- 17332728 TI - Rates of hospitalization related to traumatic brain injury--nine states, 2003. AB - Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Each year, on average, TBIs are associated with an estimated 1.1 million emergency department visits, 235,000 hospitalizations, and 50,000 deaths in the United States. For 2002, the overall rate of TBI-related hospitalization reported by the 12 states in the CDC TBI surveillance system was 79.0 per 100,000 population; across these states, however, the rates varied substantially (from 50.6 in Nebraska to 96.9 in Arizona). To update results from the CDC TBI surveillance system, CDC analyzed data from 2003, the most recent year for which data were available. This report summarizes the results of that analysis, which indicated that an estimated 28,819 persons (87.9 per 100,000 population) were hospitalized with a TBI-related diagnosis in the nine states that reported data for 2003. For all age groups combined, rates were higher among males. Age specific rates were highest among persons aged >/=75 years. Unintentional motor vehicle-traffic incidents (MV-T) and unintentional falls were the two leading causes associated with TBI-related hospitalization. The findings underscore the need for states to continue monitoring the occurrence, external causes, and risk factors for TBI and to design and implement more effective injury-prevention programs. PMID- 17332729 TI - Bloodstream infections among patients treated with intravenous epoprostenol or intravenous treprostinil for pulmonary arterial hypertension--seven sites, United States, 2003-2006. AB - Pulmonary arterial hypertension (PAH) is a life-threatening disorder characterized by elevated pulmonary artery pressure and pulmonary vascular resistance. Continuous infusion of a prostanoid, which acts as a vasodilator and anti-proliferative agent, is indicated in the treatment of patients with severe PAH. Two prostanoids are approved for intravenous (IV) use in the United States: epoprostenol (epoprostenol sodium [brand name Flolan], Gilead, Foster City, California) and treprostinil (treprostinil sodium [brand name Remodulin], United Therapeutics, Silver Spring, Maryland). These drugs are administered to PAH patients at hundreds of treatment centers in the United States. In September 2006, CDC received a report from a PAH specialist of a suspected increase in the number of gram-negative bloodstream infections (BSIs) among PAH patients treated with IV treprostinil. CDC conducted a retrospective investigation with the assistance of several state health departments and the cooperation of seven PAH treatment centers to determine the relative rates of BSI in a sample of patients treated with IV treprostinil and IV epoprostenol during 2003--2006. This report describes the results of that investigation, which indicated that, based on combined data from seven separate PAH treatment centers, pooled mean rates of BSI (primarily gram-negative BSI) were significantly higher for patients on treprostinil than for those on epoprostenol. The results do not suggest intrinsic contamination of IV treprostinil as a cause of the infections; the difference in rates might have been caused by differences in preparation and storage of the two agents, differences in catheter care practices, or differences in the anti inflammatory activity of the agents. Health-care providers who care for PAH patients should be aware of these findings. Further investigation is needed to determine the causes of the different infection rates at centers where this was observed and to determine whether such a difference exists in other PAH treatment centers. PMID- 17332730 TI - Electrolyte abnormalities and progressive renal failure in a cancer patient. PMID- 17332731 TI - Klotho: an antiaging protein involved in mineral and vitamin D metabolism. AB - Klotho gene mutation leads to a syndrome strangely resembling chronic kidney disease patients undergoing dialysis with multiple accelerated age-related disorders, including hypoactivity, sterility, skin thinning, muscle atrophy, osteoporosis, vascular calcifications, soft-tissue calcifications, defective hearing, thymus atrophy, pulmonary emphysema, ataxia, and abnormalities of the pituitary gland, as well as hypoglycemia, hyperphosphatemia, and paradoxically high-plasma calcitriol levels. Conversely, mice overexpressing klotho show an extended existence and a slow aging process through a mechanism that may involve the induction of a state of insulin and oxidant stress resistance. Two molecules are produced by the klotho gene, a membrane bound form and a circulating form. However, their precise biological roles and molecular functions have been only partly deciphered. Klotho can act as a circulating factor or hormone, which binds to a not yet identified high-affinity receptor and inhibits the intracellular insulin/insulin-like growth factor-1 (IGF-1) signaling cascade; klotho can function as a novel beta-glucuronidase, which deglycosylates steroid beta glucuronides and the calcium channel transient receptor potential vallinoid-5 (TRPV5); as a cofactor essential for the stimulation of fibroblast growth factor (FGF) receptor by FGF23. The two last functions have propelled klotho to the group of key factors regulating mineral and vitamin D metabolism, and have also stimulated the interest of the nephrology community. The purpose of this review is to provide a nephrology-oriented overview of klotho and its potential implications in normal and altered renal function states. PMID- 17332732 TI - Glomerular hyperfiltration: a new marker of metabolic risk. AB - Chronic kidney disease coexists with metabolic syndrome and this relationship may be apparent before overt manifestations of cardiovascular disease. To investigate early stages of the natural history of associations between renal function and metabolic syndrome, we phenotyped 1572 young (mean age=18.4 years), apparently healthy men for metabolic risk factors and estimated their creatinine clearance based on the Cockcroft-Gault equation. High metabolic risk (clustering of at least three metabolic risk factors) was revealed in 8.7% (137) of the subjects and was associated with a 6.9-fold increase in the odds of glomerular hyperfiltration (95% confidence interval (CI): 3.9-11.5) when compared to reference (from none to two metabolic risk factors). Overweight, elevated blood pressure, and low high-density lipoprotein (HDL) cholesterol increased the multivariate-adjusted odds ratio of glomerular hyperfiltration to 6.6 (95% CI: 3.8-11.6), 1.8 (95% CI: 1.0-3.0), and 2.5 (95% CI: 1.5-4.3), respectively. Systolic and diastolic blood pressures clustered together with leptin in the factor analysis and this blood pressure-adiposity component correlated with estimated creatinine clearance (r=0.329, P<0.0001) and explained on its own 10.2% of the variance in the estimated renal function. Our data reveal the silent epidemics of metabolic risk among young, apparently healthy men. Furthermore, the results indicate that high metabolic risk is associated with glomerular hyperfiltration before overt manifestations of cardiovascular disease. PMID- 17332733 TI - Glomerulus-specific mRNA transcripts and proteins identified through kidney expressed sequence tag database analysis. AB - The kidney glomerulus plays a crucial role in blood filtration but the molecular composition and physiology of the glomerulus is not well understood. We previously constructed and large-scale sequenced four mouse glomerular expressed sequence tag (EST) libraries from newborn and adult mouse glomeruli. Here, we compared glomerular EST profiles with whole kidney EST profiles, thereby identifying 497 transcripts corresponding to UniGene clusters that were glomerulus-enriched, that is expressed more abundantly in glomeruli than in whole kidney. These include several known protein-coding glomerulus-specific transcripts critical for glomerulus development and function, but also a large number of gene transcripts, which have not previously been shown to be expressed in the glomerulus, or implicated in glomerular functions. We used in situ hybridization to demonstrate glomerulus-specific RNA expression for six novel glomerular genes and the public Human Protein Atlas to verify glomerular protein expression for another two. The higher mRNA abundance for the eight genes in glomeruli compared with whole kidney was also verified by Taqman quantitative polymerase chain reaction. We surmise that the further characterization of these genes and proteins will increase our understanding of glomerular development and physiology. PMID- 17332734 TI - Diagnosis and salvage of an immature fistula. PMID- 17332735 TI - R990G polymorphism of calcium-sensing receptor does produce a gain-of-function and predispose to primary hypercalciuria. AB - An association between the R990G polymorphism of the CaSR gene, coding for calcium-sensing receptor, and primary hypercalciuria was found in kidney stone formers. To confirm this relationship, we investigated hypercalciuric women without stones and studied the effect of CaSR gene in human embryonic kidney cells (HEK-293). We genotyped for CaSR A986S, R990G, and Q1011E polymorphisms, 119 normocalciuric and 124 hypercalciuric women with negative history of kidney stones. Homozygous (n=2) or heterozygous (n=21) women for the 990G allele considered as one group had an increased risk to be hypercalciuric (odds ratio=5.2; P=0.001) and higher calcium excretion (P=0.005) in comparison with homozygous women for the 990R allele (n=220). HEK-293 cells were transfected with the variant allele at the three CaSR gene polymorphisms and with the most common allele with no variants. The transient increment of intracellular calcium caused by the stepwise increase of extracellular calcium was evaluated in stable transfected cells loaded with fura-2 AM. The extracellular calcium concentration producing the half-maximal intracellular calcium response was lower in HEK-293 cells transfected with the 990G allele than in those transfected with the wild type allele (P=0.0001). Our findings indicate that R990G polymorphism results in a gain-of-function of the calcium-sensing receptor and increased susceptibility to primary hypercalciuria. PMID- 17332736 TI - Phosphoinositide 3-kinase is required for high glucose-induced hypertrophy and p21WAF1 expression in LLC-PK1 cells. AB - Transforming growth factor-beta (TGF-beta), Smads, and the cyclin-dependent kinase (cdk) inhibitor p21(WAF1) are important in the pathogenesis of diabetic tubular hypertrophy. Phosphoinositide 3 kinase (PI3K)/Akt kinase activity is increased in diabetic glomerular hypertrophy. Thus, we studied the role of PI3K in high glucose (30 mM)-induced p21(WAF1), Smad2/3, and cell cycle-dependent hypertrophy in LLC-PK1 cells. We found that high glucose time-dependently (1-48 h) increased PI3K/Akt kinase activity. LY294002 (a PI3K inhibitor) attenuated high glucose-induced cell cycle-dependent (G(0)/G(1) phase) hypertrophy at 72 h while attenuating high glucose-induced p21(WAF1) gene transcription and protein expression at 36-48 h. LY294002 also attenuated high glucose-induced binding of p21(WAF1) to the cyclin E/cdk2 complex, whereas attenuating high glucose-induced TGF-beta bioactivity, Smad2/3 phosphorylation, and Smad2/3 DNA-binding activity at 36-48 h. We concluded that PI3K is required for high glucose-induced cell cycle-dependent hypertrophy, p21(WAF1) transcription and expression, p21(WAF1) binding to the cyclin E/cdk2 complex, TGF-beta bioactivity, and Smad2/3 activity in LLC-PK1 cells. PMID- 17332737 TI - The janus face of immunosuppression - de novo malignancy after renal transplantation: the experience of the Transplantation Center Munich. AB - After decades of successful organ transplantation clinicians continue to be troubled by the increasing incidence of cancers under maintenance immunosuppression. In this study, we examined rates of malignancies in 2419 renal transplant recipients transplanted in our institution between 1978 and 2005. In renal transplant recipients the cumulative incidence of cancer after 25 years was 49.3% for all tumors and 39.7% excluding non-melanoma skin cancers, compared with 21% for a normal sex- and age-matched population. The most frequent tumors observed were non-melanoma skin cancers (20.5%), kidney cancers (12.0%), and cancers of the pharynx, larynx, or oral cavity (8.2%). The general increase of cancer risk was 4.3-fold. Independent risk factors for the development of a tumor were male gender, older recipient age, the presence of preformed antibodies before transplantation, and the time on immunosuppression. Interestingly, the use of IL-2-receptor antagonists significantly reduced the tumor risk of transplant recipients. The tumor risk between immunosuppressive drugs typically used for maintenance immunosuppression was not significantly different. However, mammalian target of rapamycin (mTOR) inhibitor-based immunosuppressive protocols showed a clear tendency for lower malignancy rates. De novo malignancies following renal transplantation represent a serious problem endangering the prognosis of otherwise successfully transplanted patients. Future studies will have to address whether optimized immunosuppressive regimens including mTOR-inhibitors are capable of reducing the incidence or preventing the development of posttransplant malignancies. PMID- 17332738 TI - Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis. AB - Antibodies to double-stranded (dsDNA) are associated with systemic lupus erythematosus (SLE) and directly involved in human lupus nephritis. Information about their glomerular target antigens is inconsistent, and whether availability of target antigens, antibody specificity or avidity are nephritogenic parameters, is not determined. In this study, we analyzed renal tissue from anti-dsDNA antibody-positive lupus patients with nephritis by morphological and immunological assays, including immune electron microscopy (IEM) and colocalization IEM, an EM-based confocal microscopy assay. IEM demonstrated that antibody deposits were confined to electron dense structures (EDS) in glomerular membranes. These autoantibodies colocalized with nucleosome-binding anti-dsDNA/ histone/-transcription factor antibodies. To confirm the colocalization IEM-data, we developed a colocalization terminal deoxynucleotidyl-transferase (TdT) biotin dUTP nicked end-labeled (TUNEL) IEM assay where extracellular DNA was traced by TdT-mediated introduction of biotinylated nucleotides and autoantibodies by IEM. Results consistently demonstrated that DNA colocalized with autoantibodies in glomerular membrane-associated EDS. The colocalization IEM and colocalization TUNEL IEM assays thus demonstrate that intra-glomerular membrane-associated nucleosomes are targeted by anti-dsDNA autoantibodies in human lupus nephritis. The data provide a new approach to understand basic molecular and immunological processes accounting for antibody-mediated nephritis in human SLE. PMID- 17332739 TI - The prevalence and incidence of end-stage renal disease in Native American adults on the Navajo reservation. AB - Whereas members of the Navajo Nation are at high risk for diabetes mellitus, there are no recent published estimates of the burden of end-stage renal disease (ESRD), an important sequela of diabetes, on the Navajo Nation, a 16 million acre area in Arizona, New Mexico, and Utah with more than 200 000 tribal members. We used data from the US Renal Data System to estimate the prevalence and incidence of ESRD among Native American adults (>/=18 years) living on the Navajo Nation. For comparison, we estimated the prevalence and incidence of ESRD among all adults in the US, all Native American adults in the US, and Native American adults living in Arizona, New Mexico, Utah, and Colorado excluding those living on the Navajo Nation. The age-adjusted prevalence of ESRD in the Native American adults on the Navajo Nation was 0.63%, which was higher than in the US adults (0.19%, P<0.0001) and among the Native American adults in the US (0.36%, P<0.0001), but lower than among the other Native American adults in the Southwest (0.89%, P<0.0001). The age-adjusted incidence of ESRD in the Native American adults on the Navajo Nation was 0.11%, which was also higher than in the US adults (0.045%, P<0.0001) and among the Native American adults in the US (0.073%, P<0.0009), but lower than among the other Native American adults in the Southwest (0.17%, P<0.0003). The reasons behind these disparities merit further study. PMID- 17332740 TI - Rho GTPases regulate PRK2/PKN2 to control entry into mitosis and exit from cytokinesis. AB - Rho GTPases regulate multiple signal transduction pathways that influence many aspects of cell behaviour, including migration, morphology, polarity and cell cycle. Through their ability to control the assembly and organization of the actin and microtubule cytoskeletons, Rho and Cdc42 make several key contributions during the mitotic phase of the cell cycle, including spindle assembly, spindle positioning, cleavage furrow contraction and abscission. We now report that PRK2/PKN2, a Ser/Thr kinase and Rho/Rac effector protein, is an essential regulator of both entry into mitosis and exit from cytokinesis in HeLa S3 cells. PRK2 is required for abscission of the midbody at the end of the cell division cycle and for phosphorylation and activation of Cdc25B, the phosphatase required for activation of mitotic cyclin/Cdk1 complexes at the G2/M transition. This reveals an additional step in the mammalian cell cycle controlled by Rho GTPases. PMID- 17332741 TI - Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus. AB - The Polycomb group (PcG) proteins are essential for embryogenesis, and their expression is often found deregulated in human cancer. The PcGs form two major protein complexes, called polycomb repressive complexes 1 and 2 (PRC1 and PRC2) whose function is to maintain transcriptional repression. Here, we demonstrate that the chromodomain-containing protein, CBX8, which is part of one of the PRC1 complexes, regulates proliferation of diploid human and mouse fibroblasts through direct binding to the INK4A-ARF locus. Furthermore, we demonstrate that CBX8 is limiting for the regulation of INK4A-ARF, and that ectopic expression of CBX8 leads to repression of the Ink4a-Arf locus and bypass of senescence, leading to cellular immortalization. Gene expression and location analysis demonstrate that besides the INK4A-ARF locus, CBX8 also regulates a number of other genes important for cell growth and survival. On the basis of these results, we conclude that CBX8 is an essential component of one of the PRC1 complexes, which directly regulate the expression of numerous target genes, including the INK4A ARF locus, involved in cell-fate decisions. PMID- 17332742 TI - Composition and three-dimensional EM structure of double affinity-purified, human prespliceosomal A complexes. AB - Little is known about the higher-order structure of prespliceosomal A complexes, in which pairing of the pre-mRNA's splice sites occurs. Here, human A complexes were isolated under physiological conditions by double-affinity selection. Purified complexes contained stoichiometric amounts of U1, U2 and pre-mRNA, and crosslinking studies indicated that these form concomitant base pairing interactions with one another. A complexes contained nearly all U1 and U2 proteins plus approximately 50 non-snRNP proteins. Unexpectedly, proteins of the hPrp19/CDC5 complex were also detected, even when A complexes were formed in the absence of U4/U6 snRNPs, demonstrating that they associate independent of the tri snRNP. Double-affinity purification yielded structurally homogeneous A complexes as evidenced by electron microscopy, and allowed for the first time the generation of a three-dimensional structure. A complexes possess an asymmetric shape (approximately 260 x 200 x 195 angstroms) and contain a main body with various protruding elements, including a head-like domain and foot-like protrusions. Complexes isolated here are well suited for in vitro assembly studies to determine factor requirements for the A to B complex transition. PMID- 17332743 TI - Stationary phase reorganisation of the Escherichia coli transcription machinery by Crl protein, a fine-tuner of sigmas activity and levels. AB - Upon environmental changes, bacteria reschedule gene expression by directing alternative sigma factors to core RNA polymerase (RNAP). This sigma factor switch is achieved by regulating relative amounts of alternative sigmas and by decreasing the competitiveness of the dominant housekeeping sigma(70). Here we report that during stationary phase, the unorthodox Crl regulator supports a specific sigma factor, sigma(S) (RpoS), in its competition with sigma(70) for core RNAP by increasing the formation of sigma(S)-containing RNAP holoenzyme, Esigma(S). Consistently, Crl has a global regulatory effect in stationary phase gene expression exclusively through sigma(S), that is, on sigma(S)-dependent genes only. Not a specific promoter motif, but sigma(S) availability determines the ability of Crl to exert its function, rendering it of major importance at low sigma(S) levels. By promoting the formation of Esigma(S), Crl also affects partitioning of sigma(S) between RNAP core and the proteolytic sigma(S)-targeting factor RssB, thereby playing a dual role in fine-tuning sigma(S) proteolysis. In conclusion, Crl has a key role in reorganising the Escherichia coli transcriptional machinery and global gene expression during entry into stationary phase. PMID- 17332744 TI - Recruitment of P-TEFb (Cdk9-Pch1) to chromatin by the cap-methyl transferase Pcm1 in fission yeast. AB - Capping of nascent pre-mRNAs is thought to be a prerequisite for productive elongation and associated serine 2 phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (PolII). The mechanism mediating this link is unknown, but is likely to include the capping machinery and P-TEPb. We report that the fission yeast P-TEFb (Cdk9-Pch1) forms a complex with the cap-methyltransferase Pcm1 and these proteins colocalise on chromatin. Ablation of Cdk9 function through chemical genetics causes growth arrest and abolishes serine 2 phosphorylation on the PolII CTD. Strikingly, depletion of Pcm1 also leads to a dramatic decrease of phospho-serine 2. Chromatin immunoprecipitations show a severe decrease of chromatin-bound Cdk9-Pch1 when Pcm1 is depleted. On the contrary, Cdk9 is not required for association of Pcm1 with chromatin. Furthermore, compromising Cdk9 activity leads to a promoter-proximal PolII stalling and sensitivity to 6 azauracil, reflecting elongation defects. The in vivo data presented here strongly support the existence of a molecular mechanism where the cap methyltransferase recruits P-TEFb to chromatin, thereby ensuring that only properly capped transcripts are elongated. PMID- 17332745 TI - Notch3 and the Notch3-upregulated RNA-binding protein HuD regulate Ikaros alternative splicing. AB - Constitutive activation of the transmembrane receptor, Notch3, and loss of function of the hematopoietic transcription repressor, Ikaros (IK), play direct roles in T-cell differentiation and leukemogenesis that are dependent on pre-T cell receptor (pre-TCR) signaling. We demonstrate the occurrence of crosstalk between Notch3 and IK that results in transcriptional regulation of the gene encoding the pTalpha chain of the pre-TCR. We also show that, in the presence of the pre-TCR, constitutive activation of Notch3 in thymocytes causes increased expression of dominantnegative non-DNA-binding IK isoforms, which are able to restrain the IK inhibition of Notch3's transcriptional activation of pTalpha. This effect appears to be mediated by Notch3's pre-TCR-dependent upregulation of the RNA-binding protein, HuD. Notch3 signaling thus appears to play a critical role in the diminished IK activity described in several lymphoid leukemias. By exerting transcription-activating and transcription-repressing effects on the pTalpha promoter, Notch3 and IK cooperate in the fine-tuning of pre-TCR expression and function, which has important implications for the regulation of thymocyte differentiation and proliferation. PMID- 17332746 TI - Analysis of interactions in a tapasin/class I complex provides a mechanism for peptide selection. AB - We examined interactions in a soluble tapasin (TPN)/HLA-B*0801 complex to gain mechanistic insights into the functions of TPN. Results show that TPN acts as a chaperone by increasing the ratio of active-to-inactive peptide-deficient HLA B*0801 molecules in solution. TPN causes peptides to associate and dissociate faster owing to its effect on widening the binding groove of HLA-B*0801 molecules. Our data indicate that a TPN-assisted mechanism of peptide selection relies on disruption of conserved hydrogen bonds at the C-terminal end of the groove. Peptide sequence-dependent interactions along the entire length of the groove also play a role in this mechanism. We suggest that TPN influences presentation of antigenic peptides according to a mechanistically complicated process in which bound candidate peptides that are unable to conformationally disengage TPN from class I molecules are excluded from the repertoire. Overall, these studies unify our understanding of the functions of TPN. PMID- 17332747 TI - Acetylated YY1 regulates Otx2 expression in anterior neuroectoderm at two cis sites 90 kb apart. AB - The mouse homeobox gene Otx2 plays essential roles at each step and in every tissue during head development. We have previously identified a series of enhancers that are responsible for driving the Otx2 expression in these contexts. Among them the AN enhancer, existing 92 kb 5' upstream, directs Otx2 expression in anterior neuroectoderm (AN) at the headfold stage. Analysis of the enhancer mutant Otx2(DeltaAN/-) indicated that Otx2 expression under the control of this enhancer is essential to the development of AN. This study demonstrates that the AN enhancer is promoter-dependent and regulated by acetylated YY1. YY1 binds to both the AN enhancer and promoter region. YY1 is acetylated in the anterior head, and only acetylated YY1 can bind to the sequence in the enhancer. Moreover, YY1 binding to both of these two sites is essential to Otx2 expression in AN. These YY1 binding sites are highly conserved in AN enhancers in tetrapods, coelacanth and skate, suggesting that establishment of the YY1 regulation coincides with that of OTX2 function in AN development in an ancestral gnathostome. PMID- 17332748 TI - Structures and physiological roles of 13 integral lipids of bovine heart cytochrome c oxidase. AB - All 13 lipids, including two cardiolipins, one phosphatidylcholine, three phosphatidylethanolamines, four phosphatidylglycerols and three triglycerides, were identified in a crystalline bovine heart cytochrome c oxidase (CcO) preparation. The chain lengths and unsaturated bond positions of the fatty acid moieties determined by mass spectrometry suggest that each lipid head group identifies its specific binding site within CcOs. The X-ray structure demonstrates that the flexibility of the fatty acid tails facilitates their effective space-filling functions and that the four phospholipids stabilize the CcO dimer. Binding of dicyclohexylcarbodiimide to the O(2) transfer pathway of CcO causes two palmitate tails of phosphatidylglycerols to block the pathway, suggesting that the palmitates control the O(2) transfer process.The phosphatidylglycerol with vaccenate (cis-Delta(11)-octadecenoate) was found in CcOs of bovine and Paracoccus denitrificans, the ancestor of mitochondrion, indicating that the vaccenate is conserved in bovine CcO in spite of the abundance of oleate (cis-Delta(9)-octadecenoate). The X-ray structure indicates that the protein moiety selects cis-vaccenate near the O(2) transfer pathway against trans-vaccenate. These results suggest that vaccenate plays a critical role in the O(2) transfer mechanism. PMID- 17332749 TI - GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42. AB - Processing of the amyloid precursor protein (APP) by beta- and gamma-secretases leads to the generation of amyloid-beta (Abeta) peptides with varying lengths. Particularly Abeta42 contributes to cytotoxicity and amyloid accumulation in Alzheimer's disease (AD). However, the precise molecular mechanism of Abeta42 generation has remained unclear. Here, we show that an amino-acid motif GxxxG within the APP transmembrane sequence (TMS) has regulatory impact on the Abeta species produced. In a neuronal cell system, mutations of glycine residues G29 and G33 of the GxxxG motif gradually attenuate the TMS dimerization strength, specifically reduce the formation of Abeta42, leave the level of Abeta40 unaffected, but increase Abeta38 and shorter Abeta species. We show that glycine residues G29 and G33 are part of a dimerization site within the TMS, but do not impair oligomerization of the APP ectodomain. We conclude that gamma-secretase cleavages of APP are intimately linked to the dimerization strength of the substrate TMS. The results demonstrate that dimerization of APP TMS is a risk factor for AD due to facilitating Abeta42 production. PMID- 17332750 TI - Structure and function of the visual arrestin oligomer. AB - A distinguishing feature of rod arrestin is its ability to form oligomers at physiological concentrations. Using visible light scattering, we show that rod arrestin forms tetramers in a cooperative manner in solution. To investigate the structure of the tetramer, a nitroxide side chain (R1) was introduced at 18 different positions. The effects of R1 on oligomer formation, EPR spectra, and inter-spin distance measurements all show that the structures of the solution and crystal tetramers are different. Inter-subunit distance measurements revealed that only arrestin monomer binds to light-activated phosphorhodopsin, whereas both monomer and tetramer bind microtubules, which may serve as a default arrestin partner in dark-adapted photoreceptors. Thus, the tetramer likely serves as a 'storage' form of arrestin, increasing the arrestin-binding capacity of microtubules while readily dissociating to supply active monomer when it is needed to quench rhodopsin signaling. PMID- 17332751 TI - N- and C-terminal residues of eIF1A have opposing effects on the fidelity of start codon selection. AB - Translation initiation factor eIF1A stimulates preinitiation complex (PIC) assembly and scanning, but the molecular mechanisms of its functions are not understood. We show that the F131A,F133A mutation in the C-terminal tail (CTT) of eIF1A impairs recruitment of the eIF2-GTP-Met-tRNA(i)(Met) ternary complex to 40S subunits, eliminating functional coupling with eIF1. Mutating residues 17-21 in the N-terminal tail (NTT) of eIF1A also reduces PIC assembly, but in a manner rescued by eIF1. Interestingly, the 131,133 CTT mutation enhances initiation at UUG codons (Sui(-) phenotype) and decreases leaky scanning at AUG, while the NTT mutation 17-21 suppresses the Sui(-) phenotypes of eIF5 and eIF2beta mutations and increases leaky scanning. These findings and the opposite effects of the mutations on eIF1A binding to reconstituted PICs suggest that the NTT mutations promote an open, scanning-conducive conformation of the PIC, whereas the CTT mutations 131,133 have the reverse effect. We conclude that tight binding of eIF1A to the PIC is an important determinant of AUG selection and is modulated in opposite directions by residues in the NTT and CTT of eIF1A. PMID- 17332752 TI - A sigma-core interaction of the RNA polymerase holoenzyme that enhances promoter escape. AB - The sigma subunit of bacterial RNA polymerase (RNAP) is required for promoter specific transcription initiation and can also participate in downstream events. Several functionally important intersubunit interactions between Escherichia coli sigma(70) and the core enzyme (alpha(2)betabeta'omega) have been defined. These include an interaction between conserved region 2 of sigma(70) (sigma(2)) and the coiled-coil domain of beta' (beta' coiled-coil) that is required for sequence specific interaction between sigma(2) and the DNA during both promoter open complex formation and sigma(70)-dependent early elongation pausing. Here, we describe a previously uncharacterized interaction between a region of sigma(70) adjacent to sigma(2) called the nonconserved region (sigma(70) NCR) and a region in the N-terminal portion of beta' that appears to functionally antagonize the sigma(2)/beta' coiled-coil interaction. Specifically, we show that the sigma(70) NCR/beta' interaction facilitates promoter escape and hinders early elongation pausing, in contrast to the sigma(2)/beta' coiled-coil interaction, which has opposite effects. We also demonstrate that removal of the sigma(70) NCR results in a severe growth defect; we suggest that its importance for growth may reflect its role in promoter escape. PMID- 17332753 TI - Positioning of chemosensory clusters in E. coli and its relation to cell division. AB - Chemotaxis receptors and associated signalling proteins in Escherichia coli form clusters that consist of thousands of molecules and are the largest native protein complexes described to date in bacteria. Clusters are located at the cell poles and laterally along the cell body, and play an important role in signal transduction. Much work has been done to study the structure and function of receptor clusters, but the significance of their positioning and the underlying mechanisms are not understood. Here, we used fluorescence imaging to study cluster distribution and follow cluster dynamics during cell growth. Our data show that lateral clusters localise to specific periodic positions along the cell body, which mark future division sites and are involved in the localisation of the replication machinery. The chemoreceptor cluster positioning is thus intricately related to the overall structure and division of an E. coli cell. PMID- 17332754 TI - The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport. AB - Alcadeinalpha (Alcalpha) is an evolutionarily conserved type I membrane protein expressed in neurons. We show here that Alcalpha strongly associates with kinesin light chain (K(D) approximately 4-8x10(-9) M) through a novel tryptophan- and aspartic acid-containing sequence. Alcalpha can induce kinesin-1 association with vesicles and functions as a novel cargo in axonal anterograde transport. JNK interacting protein 1 (JIP1), an adaptor protein for kinesin-1, perturbs the transport of Alcalpha, and the kinesin-1 motor complex dissociates from Alcalpha containing vesicles in a JIP1 concentration-dependent manner. Alcalpha-containing vesicles were transported with a velocity different from that of amyloid beta protein precursor (APP)-containing vesicles, which are transported by the same kinesin-1 motor. Alcalpha- and APP-containing vesicles comprised mostly separate populations in axons in vivo. Interactions of Alcalpha with kinesin-1 blocked transport of APP-containing vesicles and increased beta-amyloid generation. Inappropriate interactions of Alc- and APP-containing vesicles with kinesin-1 may promote aberrant APP metabolism in Alzheimer's disease. PMID- 17332755 TI - PACAP type I receptor transactivation is essential for IGF-1 receptor signalling and antiapoptotic activity in neurons. AB - Insulin-like growth factor-1 (IGF-1) and pituitary adenylyl cyclase activating polypeptide (PACAP) are both potent neurotrophic and antiapoptotic factors, which exert their effects via phosphorylation cascades initiated by tyrosine kinase and G-protein-coupled receptors, respectively. Here, we have adapted a recently described phosphoproteomic approach to neuronal cultures to characterize the phosphoproteomes generated by these neurotrophic factors. Unexpectedly, IGF-1 and PACAP increased the phosphorylation state of a common set of proteins in neurons. Using PACAP type 1 receptor (PAC1R) null mice, we showed that IGF-1 transactivated PAC1Rs constitutively associated with IGF-1 receptors. This effect was mediated by Src family kinases, which induced PAC1R phosphorylation on tyrosine residues. PAC1R transactivation was responsible for a large fraction of the IGF-1-associated phosphoproteome and played a critical role in the antiapoptotic activity of IGF-1. Hence, in contrast to the general opinion that the trophic activity of IGF-1 is solely mediated by tyrosine kinase receptor associated signalling, we show that it involves a more complex signalling network dependent on the PAC1 Gs-protein-coupled receptor in neurons. PMID- 17332756 TI - MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. AB - MT1-matrix metalloproteinase (MT1-MMP) is one of the most critical factors in the invasion machinery of tumor cells. Subcellular localization to invasive structures is key for MT1-MMP proinvasive activity. However, the mechanism driving this polarized distribution remains obscure. We now report that polarized exocytosis of MT1-MMP occurs during MDA-MB-231 adenocarcinoma cell migration into collagen type I three-dimensional matrices. Polarized trafficking of MT1-MMP is triggered by beta1 integrin-mediated adhesion to collagen, and is required for protease localization at invasive structures. Localization of MT1-MMP within VSV G/Rab8-positive vesicles, but not in Rab11/Tf/TfRc-positive compartment in invasive cells, suggests the involvement of the exocytic traffic pathway. Furthermore, constitutively active Rab8 mutants induce MT1-MMP exocytic traffic, collagen degradation and invasion, whereas Rab8- but not Rab11-knockdown inhibited these processes. Altogether, these data reveal a novel pathway of MT1 MMP redistribution to invasive structures, exocytic vesicle trafficking, which is crucial for its role in tumor cell invasiveness. Mechanistically, MT1-MMP delivery to invasive structures, and therefore its proinvasive activity, is regulated by Rab8 GTPase. PMID- 17332757 TI - Role of Arabidopsis AGO6 in siRNA accumulation, DNA methylation and transcriptional gene silencing. AB - Argonautes (AGOs) are conserved proteins that contain an RNA-binding PAZ domain and an RNase H-like PIWI domain. In Arabidopsis, except for AGO1, AGO4 and AGO7, the roles of seven other AGOs in gene silencing are not known. We found that a mutation in AGO6 partially suppresses transcriptional gene silencing in the DNA demethylase mutant ros1-1. In ago6-1ros1-1 plants, RD29A promoter short interfering RNAs (siRNAs) are less abundant, and cytosine methylation at both transgenic and endogenous RD29A promoters is reduced, compared to that in ros1-1. Interestingly, the ago4-1 mutation has a stronger suppression of the transcriptional silencing phenotype of ros1-1 mutant. Analysis of cytosine methylation at the endogenous MEA-ISR, AtREP2 and SIMPLEHAT2 loci revealed that the CpNpG and asymmetric methylation levels are lower in either of the ago6-1 and ago4-1 single mutants than those in the wild type, and the levels are the lowest in the ago6-1ago4-1 double mutant. These results suggest that AGO6 is important for the accumulation of specific heterochromatin-related siRNAs, and for DNA methylation and transcriptional gene silencing, this function is partly redundant with AGO4. PMID- 17332758 TI - Chemical combination effects predict connectivity in biological systems. AB - Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured. PMID- 17332759 TI - Networks from drug-drug surfaces. PMID- 17332760 TI - The p53 family in differentiation and tumorigenesis. AB - The role of p53 as a tumour suppressor is generally attributed to its ability to stop the proliferation of precancerous cells by inducing cell-cycle arrest or apoptosis. The relatives and evolutionary predecessors of p53 - p63 and p73 - share the tumour-suppressor activity of p53 to some extent, but also have essential functions in embryonic development and differentiation control. Recent evidence indicates that these ancestral functions in differentiation control contribute to the tumour-suppressor activity that the p53 family is famous for. PMID- 17332761 TI - Clinical evaluation of changes in cornea and tear film after surgery for trachomatous upper lid entropion. AB - PURPOSE: To determine the effect of entropion surgery on corneal health in terms of surface epithelium, tear film stability, change in curvature and vision. METHODS: Prospective study; included consecutive patients with trachomatous upper lid entropion undergoing corrective surgery. Corneal opacity and other conditions that reduced vision were recorded. Best-corrected visual acuity, corneal fluorescein staining, tear film break-up time, Schirmer I test, and keratometry were performed before and after surgery. Data were analysed using Student's t test, chi(2) test, one-way ANOVA, one-sample t-test, and logistic and multiple regression. RESULTS: Thirty-six female and 15 male patients with an average age of 59.1+/-10.65 years were included. Lenticular and retinal causes resulted in blindness (P=0.008), and low vision (P=0.02), more often than entropion. At 90 days after surgery, vision improved by 0.55+/-1.48 lines (P=0.01). Superficial punctate staining of the cornea reduced by half over 1-15 days (average 6.96+/ 4.99) after surgery, and completely in 1-90 days (average 26.15+/-17.49). Tear film break-up time (range: 3-20 s preoperatively) improved significantly after surgery (P=0.005) whereas Schirmer I (range: 10-35 mm preoperatively) and keratometry values showed insignificant change. CONCLUSIONS: Surgery for entropion results in healing of superficial keratopathy, improves tear film stability, and the realigned lid margin spreads tears evenly and efficiently, thus contributing to improved vision. These changes, taking place over 1-90 days, should be kept in mind when planning intraocular surgery, keratoplasty, or keratorefractive procedures after entropion correction. PMID- 17332762 TI - Causes of blind certifications in England and Wales: April 1999-March 2000. AB - AIM: The last complete report on causes of blindness in England and Wales was for data collected during April 1990 to March 1991. This current study sought to update these figures, with data collected during April 1999 to March 2000, and examine variation in cause by age group. METHODS: In England and Wales, registration for blindness is voluntary and is initiated by certification by a consultant ophthalmologist. The main cause of blindness was ascertained where possible for all certificates completed during April 1999 to March 2000 and tabulated by age group. RESULTS: A total of 34 410 BD8 certificates were received, of which 13 788 (40%) were for people certified as blind. Different causes predominated within different age groups. Age related macular degeneration (AMD) was the lead cause in those aged 65 years and above, diabetic retinopathy was the lead cause in people of working ages (16-64 years), whereas cerebral visual impairment and disorders of the optic nerve accounted for over 40% of blind certificates completed for children. CONCLUSION: Estimates of vision impairment based on certifications for blindness in England and Wales are likely to be imprecise. They do, however, give some measure of the burden at hospital level of sight impairing eye conditions. If factors determining the imprecision remain constant, temporal monitoring of causes may enable changes and development of new conditions leading to vision impairment to be detected. PMID- 17332763 TI - Adherence to College biometry guidelines. PMID- 17332765 TI - Delayed radial keratotomy dehiscence following uneventful phacoemulsification cataract surgery. PMID- 17332766 TI - Optical coherence tomography on autologous translocation of choroid and retinal pigment epithelium in age-related macular degeneration. AB - PURPOSE: To analyse structural changes after autologous translocation of choroid and retinal pigment epithelium (RPE) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT). METHODS: We performed a prospective nonrandomised study in 29 consecutive patients, who underwent submacular surgery with translocation of an autologous full-thickness graft of RPE, Bruch's membrane, and choroid. All patients had recent loss of reading vision due to AMD. OCT was performed before surgery and at 3- and 6- month follow-up to analyse the morphological appearance of the graft and the overlying retina. RESULTS: Maximum retinal thickness decreased from mean 408 microm (standard deviation (SD) 127 microm) preoperative to mean 373 microm (SD 104 microm) at 6-month follow-up (P=0.094). In 11 cases (40%), a nearly physiological shape of the retina was seen at this time point. A macular hole persisted in two eyes after silicone oil removal. In most eyes, the highly reflective band of the graft presumably corresponding to RPE was continuous with the surrounding RPE band in all six OCT scans. Eyes with flat appearance of the graft at 6-month follow-up (<300 microm) showed a significantly better functional outcome than eyes with more prominent grafts. Interestingly, most patients did not complain about metamorphopsia, even though the graft was prominent or wrinkled in some cases. CONCLUSION: OCT is a useful tool in monitoring intra- and subretinal changes after subretinal surgery with graft translocation. We demonstrated that graft translocation may lead to a normalisation of retinal thickness and stabilisation of visual acuity. PMID- 17332767 TI - High-resolution microscopy coil MR-Eye. AB - The eye is involved in several pathologies where precise identification of the underlying condition is essential for the optimal patient care. This preliminary report presents the potential of high-resolution microscopy coil magnetic resonance imaging (HR-MRI) to undertake this task being actively used in the clinical setting. We used a commercially available MRI scanner and a microscopy surface coil. Exquisite anatomic detail of the eye and orbit with depiction of previously unobserved structures and clear demonstration of the underlying pathology was achieved. This report supports the idea that orbital imaging can be revolutionized with the introduction of HR-MRI with broad clinical implications. PMID- 17332768 TI - Dengue retinopathy manifesting with bilateral vasculitis and macular oedema. PMID- 17332769 TI - Posterior polar cataract surgery - a posterior segment approach. AB - PURPOSE: To suggest a surgical approach that would pre-empt uncontrolled posterior capsular rupture and consequent posterior segment complications associated with posterior polar cataract surgery. DESIGN: An interventional case series. METHODS: This was a prospective, interventional study undertaken at a tertiary referral ophthalmic unit. Eleven eyes of eight patients underwent planned pars plana vitrectomy, lensectomy and posterior chamber sulcus fixated intra-ocular lens implantation. Demography, presenting features, pre- and post operative visual acuities, complications and length of follow-up were recorded. A single surgical technique was performed in all the cases. RESULTS: Five male and three female patients with a mean age of 49.7 years, underwent this procedure. The median-corrected pre-operative visual acuity was 6/12 and the same post operatively was 6/6. The only major per-operative complication was one case of accidental iridectomy. Post-operatively there were transient choroidal folds in one case, mild posterior segment haemorrhage in another and retinal detachment in one patient. The mean follow-up period was 13 months. CONCLUSIONS: This surgical technique offers a relatively controlled and predictable approach to posterior polar cataract surgery compared to others described in the literature. Although this technique is not without complications, the visual outcome is usually good. PMID- 17332770 TI - Strengthening tight junctions of retinal microvascular endothelial cells by pericytes under normoxia and hypoxia involving angiopoietin-1 signal way. AB - PURPOSE: To determine the effects of pericytes and angiopoietin-1 on the expression of occludin and zonula occludens-1 (ZO-1) in retinal endothelial cells (ECs) under both normoxic and hypoxic conditions. METHODS: Rat primary retinal microvascular ECs were cultured under normoxia or hypoxia in either absence or presence of pericytes conditioned medium (PCM). PCM was pretreated with or without angiopoietin-1 neutralizing antibody. Immuofluorescent staining, Western blot and RT-PCR were used to detect the alterations of occludin and ZO-1 expression. RESULTS: Under normoxia, PCM strengthened occludin and ZO-1 immunofluorescent staining at cytomembrane as well as increased their expression at both protein and mRNA level. When pretreated with angiopoietin-1 neutralizing antibody, occludin upregulation induced by PCM was significantly blocked at protein level (62%) and mRNA level (34%). Under hypoxia, the continuity of occludin and ZO-1 staining at cell boundaries was disrupted consistent with a decrease of their protein level by 31 and 27%, respectively. Also occludin and ZO 1 mRNA level decreased by 46 and 57%, respectively. PCM was observed to partially increase expression of occludin at protein and mRNA level. Angiopoietin-1 antibody slightly inhibited (16%) PCM induced occludin mRNA increase under hypoxia. CONCLUSION: Pericytes improved the integrity of endothelial barrier through inducing occludin and ZO-1 expression at protein and mRNA level under normoxia. Under hypoxia, pericytes could partially reverse occludin decrease. These protecting effects of pericytes on endothelial barrier were at least in part mediated by angiopoietin-1. PMID- 17332771 TI - Penetration of topically applied levofloxacin into eyes with thin-wall filtering bleb after trabeculectomy. AB - PURPOSE: To investigate the comparative penetration of 0.3% levofloxacin eye drops into the aqueous humour between cataract patients with or without (control) thin-wall filtering blebs. METHODS: One drop of 0.3% levofloxacin was administered to the eyes at 30-min intervals for 3.5 h before phacoemulcification for both groups. Aqueous humour samples (0.1-0.2 ml) were aspirated during surgery. The concentration of levofloxacin in the aqueous humour was determined by high-performance liquid chromatography. The Student's t-test, Pearson correlation, and chi(2) test were used to compare the data of the two groups. A P<0.05 was required for results to be considered statistically significant. RESULTS: The levofloxacin concentration in the aqueous humour was significantly increased (P<0.0001) in the bleb (mean+SD: 3.7+/-2.3 microg/ml) vscontrol group (0.4+/-0.2 microg/ml). Intraocular pressure and the bleb area were not correlated with levofloxacin concentration. CONCLUSION: The presence of thin-wall filtering blebs increases intraocular penetration of topically administered levofloxacin. PMID- 17332773 TI - Constitutive autophagy: vital role in clearance of unfavorable proteins in neurons. AB - Investigations pursued during the last decade on neurodegenerative diseases have revealed a common mechanism underlying the development of such diseases: conformational disorder of certain proteins leads to the formation of misfolded protein oligomers, which subsequently develop into large protein aggregates. These aggregates entangle other denatured proteins and lipids to form disease specific inclusion bodies. The failure of the ubiquitin-proteasome system to shred the protein aggregates has led investigators to focus their attention to autophagy, a bulk degradative system coupled with lysosomes, which is involved in non-selective shredding of large amounts of cytoplasmic components. Research in this field has demonstrated the accumulation of autophagic vacuoles and intracytoplasmic protein aggregates in patients with various neurodegenerative diseases. Although autophagy fails to degrade large protein aggregates once they are formed in the cytoplasm, drug-induced activation of autophagy is effective in preventing aggregate deposition, indicating that autophagy significantly contributes to the clearance of aggregate-prone proteins. The pivotal role of autophagy in the clearance of aggregate-prone proteins has been confirmed by a deductive approach using a brain-specific autophagy-ablated mouse model. In this review, we discuss the consequences of autophagy deficiency in neurons. PMID- 17332774 TI - Insulin-like growth factor signaling regulates zebrafish embryonic growth and development by promoting cell survival and cell cycle progression. AB - Although much is known about the global effects of insulin-like growth factor 1 receptor (IGF1R)-mediated signaling on fetal growth and the clinical manifestations resulting from IGF/IGF1R deficiencies, we have an incomplete understanding of the cellular actions of this essential pathway during vertebrate embryogenesis. In this study, we inhibited IGF1R signaling during zebrafish embryogenesis using antisense morpholino oligonucleotides or a dominant-negative IGF1R fusion protein. IGF1R inhibition resulted in reduced embryonic growth, arrested development and increased lethality. IGF1R-deficient embryos had significant defects in the retina, inner ear, motoneurons and heart. No patterning abnormalities, however, were found in the brain or other embryonic tissues. At the cellular level, IGF1R inhibition increased caspase 3 activity and induced neuronal apoptosis. Coinjection of antiapoptotic bcl2-like mRNA attenuated the elevated apoptosis and rescued the retinal and motoneuron defects, but not the developmental arrest. Subsequent cell cycle analysis indicated an increased percentage of cells in G1 and a decreased percentage in S phase in IGF1R-deficient embryos independent of apoptosis. These results provide novel insight into the cellular basis of IGF1R function and show that IGF1R signaling does not function as an anteriorizing signal but regulates embryonic growth and development by promoting cell survival and cell cycle progression. PMID- 17332775 TI - Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis. AB - Most cell death stimuli trigger the mitochondrial release of cytochrome c and other cofactors that induce caspase activation and ensuing apoptosis. Apoptosis is also associated with massive mitochondrial fragmentation and cristae remodeling. Dynamin-related protein 1 (Drp1), a protein of the mitochondrial fission machinery, has been reported to participate in apoptotic mitochondrial fragmentation. Several theories explaining the mechanisms of cytochrome c release have been proposed. One suggests that it relies on the activation of Drp1 mediated mitochondrial fission. Here, we report that downregulation of Drp1 inhibits fragmentation of the mitochondrial network and partially prevents the release of cytochrome c but fails to prevent the release of other mitochondrial factors such as second mitochondria-derived activator of caspase/direct IAP binding protein with low pI, Omi/HtrA2, adenylate kinase 2 and deafness dystonia peptide/TIMM8a. An explanation for the prevention of cytochrome c release is provided by our observation that inhibiting Drp1-mediated mitochondrial fission prevents the mitochondrial release of soluble OPA1 that was proposed to regulate cristae remodeling and complete cytochrome c release during apoptosis. Finally, we observed that downregulation of Drp1 delays but does not inhibit apoptosis, suggesting that mitochondrial fragmentation is not a prerequisite for apoptosis. PMID- 17332776 TI - C-Raf antagonizes apoptosis induced by IFN-alpha in human lung cancer cells by phosphorylation and increase of the intracellular content of elongation factor 1A. AB - Interferon alpha (IFNalpha) induces both apoptosis and a counteracting epidermal growth factor Erk-dependent survival response in cancer cells. In this report, IFNalpha increased eukaryotic elongation factor 1A (eEF-1A) protein expression by inhibition of eEF-1A degradation via a proteasome-dependent pathway. The reduction of the expression level of eEF-1A by RNA interference enhanced the apoptosis induced by IFNalpha on the same cells. Moreover, IFNalpha induced the phosphorylation of both serine and threonine in eEF-1A. These effects were paralleled by an increased co-immunoprecipitation and colocalization of eEF-1A with C-Raf. The suppression of C-Raf kinase activity with the inhibitor BAY 43 9006 completely antagonized the increase of both eEF-1A phosphorylation and expression and of C-Raf/eEF-1A colocalization induced by IFNalpha and enhanced apoptosis and eEF-1A ubiquitination. Cell transfection with the mutated K48R ubiquitin increased EF-1A expression and desensitized tumor cells to the modulating effects of IFNalpha. The dynamic simulation of 3Dstructure of eEF-1A identified putative serine and threonine phosphorylation sites. In conclusion, the interaction between eEF-1A and C-Raf increases eEF-1A stability and induces a survival activity. PMID- 17332777 TI - Antitumor activity of dual-specific T cells and influenza virus. AB - Activation and expansion of T cells are important in disease resolution, but tumors do not usually satisfy these immune requirements. Therefore, we employed a novel strategy whereby dual-specific T cells were generated that could respond to both tumor and influenza virus, reasoning that immunization with influenza virus would activate and expand tumor-specific cells, and inhibit tumor growth. Dual specific T cells were generated by gene modification of influenza virus-specific mouse T cells with a chimeric gene-encoding reactivity against the erbB2 tumor associated antigen. Dual-specific T cells were demonstrated to respond against both tumor and influenza in vitro, and expanded in vitro in response to influenza to a much greater degree than in response to tumor cells. Following adoptive transfer and immunization of tumor-bearing mice with influenza virus, dual specific T cells expanded greatly in numbers in the peritoneal cavity and spleen. This resulted in a significant increase in time of survival of mice. However, tumors were not eradicated, which may have been due to the observed poor penetration of tumor by T cells. This is the first demonstration that the potent immunogenic nature of an infectious agent can be utilized to directly impact on T cell expansion and activity against tumor in vivo. PMID- 17332778 TI - The metabolic syndrome: an introduction. PMID- 17332780 TI - Characteristics of metabolically obese normal-weight (MONW) subjects. AB - The existence of a subgroup of normal-weight individuals displaying obesity related phenotypic characteristics was first proposed in 1981. These individuals were identified as metabolically obese but normal weight (MONW). It was hypothesized that these individuals might be characterized by hyperinsulinemia and (or) insulin resistance, as well as by hypertriglyceridemia and high blood pressure despite having a body mass index (BMI) < 25 kg/m2. Such characteristics could confer upon MONW subjects a higher cardiovascular risk; however, scientific data on MONW subjects are scarce since only 9 publications are directly related to this topic. Despite differences in the criteria for identifying MONW subjects and the small number of subjects involved in most of these studies, their consistent results indicate that: (i) the prevalence of the MONW syndrome ranges between 5% and 45%, depending on the criteria used, age, BMI, and ethnicity; (ii) when compared with control subjects, MONW subjects display an altered insulin sensitivity, a higher abdominal and visceral adiposity, a more atherogenic lipid profile, a higher blood pressure, and a lower physical activity energy expenditure; and (iii) MONW subjects are at higher risks for type 2 diabetes and cardiovascular diseases. PMID- 17332781 TI - Metabolic syndrome in youth: current issues and challenges. AB - The current paper reviews the important issues and challenges facing children and adolescents with the metabolic syndrome (MetS). Studies suggest that the MetS and its risk components may be on the rise in children along with rising rates of obesity; however, further study remains warranted. The topics reviewed encompass the definition of the syndrome, its prevalence, clustering and tracking of metabolic risk factors, the role of physical activity and diet in the development of the MetS, criticisms and utility of the MetS definition, and special considerations needed in the pediatric population. Physical activity and diet may play important roles in the MetS; however, research with precise measurements of activity, diet, and metabolic outcomes is needed. The paper concludes by emphasizing that regardless of one's position in the ongoing debate about the MetS, the long-term risks attributable to each individual risk component are real. The abnormality of one component should automatically prompt the screening of other components. Among children and adolescents, lifestyle modification should always serve as the frontline strategy. Prevention during childhood is key to the largest possible impact on adult health at the population level. PMID- 17332782 TI - The evolving definitions and increasing prevalence of the metabolic syndrome. AB - The metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that predisposes an individual to a greater risk of developing coronary heart disease and type 2 diabetes. The condition is widespread among adults from developed nations, and progresses in frequency with age. In recent years, several organizations have proposed diagnostic criteria that could be used by clinical practitioners or for research purposes. While the core components of the MetS have generally been sustained among the various proposed definitions, the number of features required for the MetS to be diagnosed and the cut-off points indicating metabolic perturbations have differed quite significantly between organizations. This has led to considerable confusion among clinicians and health professionals. The present review aims to discuss the different definitions of the MetS, focusing on their application in clinical or research settings. A brief overview of the increasing prevalence of the MetS will also be presented. PMID- 17332783 TI - Metabolic syndrome and its association with morbidity and mortality. AB - The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that are associated with increased risk of diabetes, cardiovascular disease (CVD), and all-cause mortality; however, it is clear that considerable variation exists in these relationships. Given that the prevalence of MetS increases with age, is higher in men than in women, and varies with race and ethnicity, a number of questions about the clinical application of MetS in predicting morbidity and mortality in diverse populations remain unanswered. Thus, in this review, we compare the ability of MetS to predict health risk across age, sex, race, and ethnicity, and in primary versus secondary prevention subgroups to explore these relationships. Furthermore, as there is currently no universal MetS criteria, we also discuss differences in the prediction of morbidity and mortality in studies that used different criteria to define MetS. At present, further research is necessary to examine the health risks associated with (i) different combinations of MetS components in diverse populations, (ii) the relative importance of each MetS component in predicting different health outcomes, and (iii) the independent contribution of MetS in predicting risk of morbidity and mortality beyond that incurred by other risk factors. PMID- 17332784 TI - Nutritional strategies in the prevention and treatment of metabolic syndrome. AB - The metabolic syndrome (MetS) is a clustering of metabolic abnormalities that increase the risk of developing atherosclerotic cardiovascular disease and type 2 diabetes. The exact etiology remains unclear, but it is known to be a complex interaction between genetic, metabolic, and environmental factors. Among environmental factors, dietary habits are of central importance in the prevention and treatment of this condition. However, there is currently no firm consensus on the most appropriate dietary recommendations. General recommendations include decreasing obesity, increasing physical activity, and consuming an anti atherogenic diet, and have traditionally focused on low total fat intake. A major problem with the focus on low fat is that high-carbohydrate diets can contribute to increasing triglyceride and decreasing high-density lipoprotein (HDL) concentrations. Low-carbohydrate diets have been popular in recent years. However, such diets are typically higher in saturated fat and lower in fruits, vegetables, and whole grains than national dietary recommendations. More recently the quality of carbohydrate has been studied in relation to MetS, including a focus on dietary fiber and glycemic index. Similarly, there has been a move from limiting total fat to a focus on the quality of the fat, with evidence of beneficial effects of replacing some carbohydrate with monounsaturated fat. Other nutrients examined for possible importance include calcium, vitamin D, and magnesium. Together, the evidence suggests that the components of diet currently recommended as "healthy" are likely also protective against MetS, including low saturated and trans fat (rather than low total fat) and balanced carbohydrate intake rich in dietary fiber, as well as high fruit and vegetable intake (rather than low total carbohydrate); and the inclusion of low-fat dairy foods. Accelerating research on gene-diet interactions is likely to contribute interesting information that may lead to further individualized dietary guidance in the future. PMID- 17332785 TI - Regulation of postprandial lipemia: an update on current trends. AB - People spend a large percentage of their waking hours in the postprandial state. Postprandial lipemia is associated with disruptions in lipoprotein metabolism and inflammatory factors, cardiovascular disease, MetS, and diabetes. Commonly, the dietary sources of fat exceed the actual needs and the tissues are faced with the excess, with accumulation of chylomicrons and remnant particles. This review will summarize recent findings in postprandial lipemia research with a focus on human studies. The effects of dietary factors and other meal components on postprandial lipemia leads to the following question: do we need a standardized oral lipid tolerance test (OLTT)? An overview of recent findings on FABP2, MTP, LPL, apoAV, and ASP and the effects of body habitus (sex influence and body size), as well as exercise and weight loss, on postprandial lipemia will be summarized. PMID- 17332786 TI - Physical activity in prevention and treatment of the metabolic syndrome. AB - Randomised controlled trials have shown that exercise training has a mild or moderate favourable effect on many metabolic and cardiovascular risk factors that constitute or are related to the metabolic syndrome (MetS). Epidemiological studies suggest that regular physical activity prevents type 2 diabetes, cardiovascular disease, and premature mortality in large part through these risk factors. Although randomized controlled trials with the prevention or treatment of the MetS as the main outcome have not been published, several large randomized controlled trials provide strong evidence that favourable lifestyle changes, including regular physical activity, are effective in the prevention of type 2 diabetes in individuals who are overweight and have impaired glucose tolerance. Compliance with the current recommendations to increase the total volume of moderate-intensity physical activity and to maintain good cardiorespiratory and muscular fitness appears to markedly decrease the likelihood of developing the MetS, especially in high-risk groups. Walking is the most common form of physical activity--it improves health in many ways and is generally safe. Therefore, brisk walking for at least 30 min daily can be recommended as the principal form of physical activity at the population level. If there are no contraindications, more vigorous physical exercise or resistance training should also be considered to obtain additional health benefits. Unstructured and low-intensity physical activity may also decrease the likelihood of developing the MetS, especially when substituted for sedentary behaviours such as watching television. The measurement of maximal oxygen consumption may provide an efficient means to target even individuals with relatively few metabolic risk factors who may benefit from more intensive intervention. PMID- 17332787 TI - Genetics of the metabolic syndrome. AB - The concept of a metabolic syndrome (MetS), a cluster of pre-clinical metabolic alterations commonly associated with obesity, is the object of much debate. Genetic studies have the potential to contribute to some of the key questions, including the true nature of the cluster of pre-clinical features and whether it is associated with human genetic variation. This review summarizes the evidence for the presence of familial aggregation for the individual components of MetS and their heritability levels. It also provides an overview of the studies that have dealt with candidate genes for MetS. Potential leads from genome-wide linkage scans are also discussed. The assumption is made that obesity, ectopic fat deposition and abnormal adipose tissue metabolism are responsible for alterations in lipid metabolism, which in turn generates the commonly observed pre-clinical shifts in glucose tolerance, lipids and lipoprotein profile, blood pressure, inflammatory markers, endothelial function, and a prothrombotic state. Progress in the understanding of the genetic basis of MetS should occur as soon as a consensus is reached on the true nature of MetS, its components and diagnostic criteria. PMID- 17332788 TI - Contraction-mediated glucose uptake is increased in men with impaired glucose tolerance. AB - Exercise superimposed on insulin stimulation is shown to increase muscle glucose metabolism and these two stimuli have synergistic effects. The objective of this study was to investigate glucose infusion rates (GIR) in groups with a wide variation in terms of insulin sensitivity during insulin stimulation alone and with superimposed exercise. Patients with type 2 diabetes, subjects with impaired glucose tolerance (IGT), healthy controls, and endurance-trained subjects were studied. The groups were matched for age and lean body mass (LBM), and differed in peak oxygen uptake (VO2 peak), body fat percentage, body mass index (BMI), fasting plasma glucose concentration, and oral glucose-tolerance test (OGTT). Each subject underwent a two-step sequential hyperinsulinemic, euglycemic clamp. During the last 30 min of the 2nd clamp step, subjects exercised on a bicycle at 43% +/- 2% of VO2 peak. In agreement with the OGTT data, the presence of different GIR during insulin stimulation alone demonstrated varying levels of insulin sensitivity between groups. However, the impairment of GIR in IGT observed during insulin stimulation alone was abolished compared to controls when exercise was superimposed on insulin stimulation. Humans with IGT are resistant to insulin-stimulated but not to exercise-induced glucose uptake. PMID- 17332789 TI - Short-term effects of a non-dieting lifestyle intervention program on weight management, fitness, metabolic risk, and psychological well-being in obese premenopausal females with the metabolic syndrome. AB - Lifestyle modification has been widely acknowledged as the primary treatment for the metabolic syndrome (MetS). We examined the short-term effects of a non dieting lifestyle intervention program, within the theoretical psychological framework of self-determination theory (SDT), on metabolic fitness and psychological well-being among premenopausal, clinically obese women. A secondary analysis of a randomized, controlled, 3 month, intensive, community-based lifestyle intervention study was performed on 31 pre-menopausal obese women with the MetS (56.4% of original study sample). These participants had been randomly allocated to a non-dieting lifestyle intervention group (n = 17) or waiting list control (n = 14). Among participants who completed repeat anthropometric and cardiorespiratory fitness measurements after 3 months intervention, the lifestyle intervention group showed a significant improvement in VO2 (mL.kg(-1).min(-1)) compared with control (test for interaction, p = 0.003). No significant difference was found for body mass. Metabolic improvements were evident for diastolic blood pressure and high-density lipoprotein cholesterol in both groups. The lifestyle intervention group also showed significantly improved general psychological well-being compared with the control group (test for interaction, p = 0.0005). All of the psychological well-being subscales showed significant favourable changes in the intervention group as compared with controls. This short-term, non-dieting lifestyle intervention, consistent with the "Health at Every Size" (HAES) obesity treatment paradigm, significantly improved cardiorespiratory fitness and psychological well-being. Metabolic risk tended to improve after 3 months intervention with no significant difference in the resolution of the MetS between intervention and control participants. PMID- 17332790 TI - Cardiorespiratory fitness and metabolic syndrome: US National Health and Nutrition Examination Survey 1999-2002. AB - Increasing physical activity is recommended as a therapeutic lifestyle change in the treatment of metabolic syndrome (MetS); however, little evidence exists for a relationship between cardiorespiratory fitness (CRF) and MetS in representative samples. Using data from the US National Health and Nutrition Examination Survey, 1999-2002, the relationship between CRF and MetS was examined in 692 men and 608 women between the ages of 18 and 49 y who were free of major disease and disability. In men, the odds of MetS were significantly lower in moderate and high CRF categories versus the low CRF category, whereas in women there were no significant relationships between CRF and MetS. PMID- 17332801 TI - NIH State-of-the-Science Conference Statement on Tobacco Use: Prevention, Cessation, and Control. AB - OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on tobacco use: prevention, cessation and control. PARTICIPANTS: A non-DHHS, non-advocate 14 member panel included experts in the fields of medicine, general and pediatric psychiatry, addiction medicine, nursing, social work, population science, cancer prevention, minority health and health disparities, clinical study methodology, clinical epidemiology, and a public representative. A listing of the panel members and their institutional affiliations is included in the draft conference statement. In addition, 15 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the RTI International-University of North Carolina Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: Tobacco use remains a very serious public health problem. Coordinated national strategies for tobacco prevention, cessation, and control are essential if the United States is to achieve the Healthy People 2010 goals. Most adult smokers want to quit, and effective interventions exist. However, only a small proportion of tobacco users try treatment. This gap represents a major national quality-of-care problem. Many cities and states have implemented effective policies to reduce tobacco use; public health and government leaders should learn from these experiences. Because smokeless tobacco use may increase in the United States, it will be increasingly important to understand net population harms related to use of smokeless tobacco. Prevention, especially among youth, and cessation are the cornerstones of strategies to reduce tobacco use. Tobacco use is a critical and chronic problem that requires close attention from health care providers, health care organizations, and research support organizations. PMID- 17332802 TI - NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention. AB - OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on Multivitamin/Mineral Supplements and Chronic Disease Prevention. PARTICIPANTS: A non-DHHS, non advocate 13-member panel included experts in the fields of food science and human nutrition, biostatistics, biochemistry, toxicology, geriatric medicine, family medicine, pediatrics and pediatric endocrinology, cancer prevention, epidemiology, disease prevention and health promotion, and consumer protection. In addition, 19 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by The Johns Hopkins University Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: Use of multivitamins/minerals (MVMs) has grown rapidly over the past several decades, and dietary supplements are now used by more than half of the adult population in the United States. In general, MVMs are used by individuals who practice healthier lifestyles, thus making observational studies of the overall relationship between MVM use and general health outcomes difficult to interpret. Despite the widespread use of MVMs, we still have insufficient knowledge about the actual amount of total nutrients that Americans consume from diet and supplements. This is at least in part due to the fortification of foods with these nutrients, which adds to the effects of MVMs or single-vitamin or single mineral supplements. Historically, fortification of foods has led to the remediation of vitamin and mineral deficits, but the cumulative effects of supplementation and fortification have also raised safety concerns about exceeding upper levels. Thus, there is a national need to improve the methods of obtaining accurate and current data on the public's total intake of these nutrients in foods and dietary supplements. In systematically evaluating the effectiveness and safety of MVMs in relation to chronic disease prevention, we found few rigorous studies on which to base clear conclusions and recommendations. Most of the studies we examined do not provide strong evidence for beneficial health-related effects of supplements taken singly, in pairs, or in combinations of three or more. Within some studies or subgroups of the study populations, there is encouraging evidence of health benefits, such as increased bone mineral density and decreased fractures in postmenopausal women who use calcium and vitamin D supplements. However, several other studies also provide disturbing evidence of risk, such as increased lung cancer risk with beta carotene use among smokers. The current level of public assurance of the safety and quality of MVMs is inadequate, given the fact that manufacturers of these products are not required to report adverse events and the FDA has no regulatory authority to require labeling changes or to help inform the public of these issues and concerns. It is important that the FDA's purview over these products be authorized and implemented. Finally, the present evidence is insufficient to recommend either for or against the use of MVMs by the American public to prevent chronic disease. The resolution of this important issue will require advances in research and improved communication and collaboration among scientists, health care providers, patients, the pharmaceutical and supplement industries, and the public. PMID- 17332803 TI - [Patients as teachers]. PMID- 17332804 TI - [What does function in rehabilitation?]. PMID- 17332805 TI - [The house of shame and the boys in Akerselva]. PMID- 17332806 TI - [Infection tracing]. PMID- 17332807 TI - [Physicians' experience with and attitudes to interaction between health care levels]. AB - BACKGROUND: We have studied physicians' experience with and attitudes to interaction between health care levels, and their opinions on how this can be improved. MATERIAL AND METHODS: Three focus groups were established. They consisted of 15 male and 2 female physicians with 3 months to 28 years of experience. Interviews with the participants were transcribed and qualitatively analysed. RESULTS: Physicians had different opinions on which characteristics are important to establish a good professional interaction, and their opinions varied according to which health care level they represent. While GPs emphasised confidence, respect, knowledge of each other and accessibility, that is a relational perspective; the local hospital physicians put more emphasis on capacity, i.e. competence, stability and accessibility. Physicians at the central Hospital emphasized capacity and structure, i.e. their own and collaborators' professional interest, accessibility and formalised structures for interactions. A sense of personal knowledge and verbal and written contact was important, but guidelines and treatment plans were also considered to be important for interaction. There was a strong ownership to the individual patient across all three levels, which was an unexpected finding. CONCLUSIONS: Good interaction seems to be a balance between the relational perspective, with emphasis on dialogue, structural arrangements, accessibility and continuity and professional competence. In addition, there is a need to clarify responsibilities for each patient. PMID- 17332808 TI - [Biopsies of the endoscopically normal colon]. AB - BACKGROUND: The importance of biopsies of the endoscopically normal colonic mucosa is controversial. MATERIAL AND METHODS: All patients who underwent total colonoscopy at St. Olav"s Hospital in 2004 were considered for inclusion if their colonoscopy was normal. Patients who were already enrolled in follow-up protocols were excluded. Biopsy practice and histological findings were recorded. RESULTS: Biopsies were taken in 266 of 738 normal colonoscopies (36%) The number of biopsies per colonoscopy varied from 1 to 16 (median 6). Biopsies from 8 of the 266 patients (3.0%) showed histological abnormalities of certain clinical significance. Seven of the 8 patients were investigated because of diarrhoea. In addition, histological abnormalities of limited clinical significance were found in biopsies from 13 of the patients (4.9%). INTERPRETATION: Use of biopsy in the endoscopically normal colon varied considerably. Taking biopsies in patients without diarrhoea was of minor clinical importance. Guidelines for taking biopsies of the endoscopically normal colon are desirable. PMID- 17332809 TI - [Khat--a new drug of abuse in Norway]. AB - BACKGROUND: The stimulating drug, Khat, is a drug of abuse that has become known in Norway due to increased immigration from East-Africa, especially Somalia. METHOD: Review of recent literature. RESULTS: Khat is present in leaves from the tree Catha Edulis and is taken by chewing the leaves. The biologically active compounds are cathinone, cathine and norephedrine. Analysis of cathinone in urine can be performed at the Norwegian Institute of Public Health. The effects of khat are similar to, but weaker than those of amphetamine. Khat stimulates the central nervous system causing increased alertness, euphoria and occasionally psychosis, and increases activity in the peripheral sympathetic nervous system leading to palpitations, increased blood pressure, large pupils and red eyes. Tannin in khat damages teeth and causes constipation. With increased use of khat in the society it is important for the clinician to have some knowledge of the effects of khat. PMID- 17332810 TI - [Cannabis and cannabinoids as drugs]. AB - BACKGROUND: Cannabis has been used throughout human history. Delta (9) tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. THC metabolises to 11-OH-THC and further to THC-acid, which is an inactive metabolite. We present an overview of the pharmacokinetics and pharmacodynamics of cannabinoids. MATERIAL AND METHOD: This article is based on selected literature with an emphasis on the pharmacodynamics of cannabinoids. RESULTS AND INTERPRETATION: It has been demonstrated that mammalian tissues express cannabinoid receptors (CB1, CB2 and most probably CB3) and endogenous ligands for these. Knowledge of these receptors has lead to the development of components that stimulate (CB-agonists) or block their function (CB-antagonists). This opens up for the study of any potential therapeutic effects of cannabinoids. Research on a possible therapeutic potential of cannabinoids should however not overshadow the well-documented negative effects of cannabis; i.e. impaired cognitive functions, intoxication and an increased risk for development of psychosis and psychotic symptoms. PMID- 17332811 TI - [Cannabis affects driving skills]. AB - Delta (9)-tetrahydrocannabinol (THC), the most important psychoactive substance in cannabis, is frequently detected in blood from apprehended drivers suspected for drugged driving. Both experimental and epidemiological studies have demonstrated the negative effects of THC upon cognitive functions and psychomotor skills. These effects could last longer than a measurable concentration of THC in blood. Culpability studies have recently demonstrated an increased risk of becoming responsible in fatal or injurious traffic accidents, even with low blood concentrations of THC. It has also been demonstrated that there is a correlation between the degree of impairment, the drug dose and the THC blood concentration. It is very important to focus on the negative effect of cannabis on fitness to drive in order to prevent injuries and loss of human life and to avoid large economic consequences to the society. PMID- 17332812 TI - [An outbreak of Yersinia enterocolitica O:9-infection]. AB - BACKGROUND: Yersiniosis is a zoonosis that is transmitted from pigs to humans. In January 2006 more cases of Yersinia enterocolitica enterocolitis than expected were reported in Norway. The fact that the isolates belonged to the O:9 serogroup, which is rare in Norway, and the geographical and temporal clustering of the cases, pointed to an outbreak. We have conducted a retrospective study of 11 patients who were diagnosed during this outbreak. MATERIAL AND METHODS: The material is based upon applicants' information, patient journals and a questionnaire. In order to disclose the source of infection, a case-control survey was performed. RESULTS: Nine of the 11 patients had enterocolitis and two had septicaemia, both of whom died following a few days of treatment. One patient presented with pseudo- appendicitis while another developed monoarthritis, which persisted for more than three months after the debut of symptoms Treatment with antibiotics was offered in six cases. The case-control analysis indicated that brawn was the probable source of infection. INTERPRETATION: This is the first reported Norwegian outbreak of Y. enterocolitica O:9 disease. The incubation time, disease duration and frequency of intestinal and immunological complications corresponds with previously published data. The frequency of septicaemia exceeds several previously reported outbreaks and retrospective studies of sporadic cases. PMID- 17332813 TI - [When during the day are patients admitted to emergency psychiatric department?]. PMID- 17332814 TI - [Functional assessment in rehabilitation]. AB - The Norwegian Ministry of Health and Care Services currently defines rehabilitation as: a well planned, goal-oriented, time-limited process, where several professions or services cooperate in assisting individuals to use their own efforts to achieve best possible functioning and coping capabilities, to become independent and to participate in society. This understanding of rehabilitation includes some important changes compared to previous definitions. One is an acknowledgement of the disabled person as an expert on his/her life, who should be involved in decisions concerning rehabilitation goals and interventions. Another is an increased focus on activity and participation in community as important goals. Continuous evaluation of the content, process and outcomes of rehabilitation is needed. An important step towards an evidence-based practice in this field is the implementation of valid and systematic assessments in clinical practice. This conceptualisation of rehabilitation requires use of individualised instruments that capture the patients' priorities and evaluations. PMID- 17332815 TI - [Rehabilitation integrated in acute medical treatment]. AB - BACKGROUND: Rehabilitation integrated in acute medical treatment is of great importance to patients with acute cerebral stroke and to frail elderly people admitted to hospital with acute medical conditions or fractures. We will focus on the latter group, which receives the least attention, but steadily increases. METHODS: MEDLINE-search for relevant literature published during the last 15 years, and own clinical experience. RESULTS AND CONCLUSIONS: Results from randomized clinical studies indicate that early geriatric rehabilitation, integrated in the acute treatment of elderly frail patients with acute diseases or hip fractures, is more effective than treatment in general medical or orthopedic wards. Geriatric intervention does not seem to increase costs. The beneficial effects consist of reduced incidence, duration and severity of delirium; fewer iatrogenic complications, better functional capacity and in some studies reduced mortality without increasing the need for institutionalization. Prerequisites for success are adequate patient selection and dedicated geriatric and rehabilitation units with full treatment responsibility. Up to 2050, there will be a dramatic increase in the number of elderly in Norway. Restructuring and reorganization of medical and orthopedic hospital departments are some of the measures required to meet this challenge. PMID- 17332816 TI - [Rehabilitation of chronic myofascial pain disorders]. AB - BACKGROUND: Chronic musculoskeletal pain of diffuse origin affects many, and at a significant cost. Evidence-based guidelines for therapeutic interventions are presented and exemplified. MATERIAL AND METHODS: 200 patients with chronic myofascial pain and/or fibromyalgia who participated in a 4-week multidimensional rehabilitation programme, were included in the study. The programme included education and pain management in a cognitive setting, various forms of aerobic exercises, myofascial pain treatment, relaxation and medication as needed. The patients filled in questionnaires on arrival, at follow-up after six and 12 months and at discharge. They completed visual analogue scales (pain, fatigue, sleep problems, depression), the Nottingham Health Profile, the Fibromyalgia Impact Questionnaire, global subjective improvement, and during the follow-up period also the physical activity level, changes in quality of life and occupational workload. Work capacity, a tender point count and whether patients met the diagnostic criteria for fibromyalgia were assessed at baseline and at discharge. RESULTS: Significant improvements were seen in all variables throughout the follow-up period. 30% of the fibromyalgia patients no longer met the diagnostic criteria at discharge. There was a significant increase in quality of life over time. After one year, more patients had returned to work and fewer were off sick, but there was also an increased number on disability pensions. The majority did exercise training on a regular basis. INTERPRETATION: Our findings confirm the existing evidence-based guidelines by showing that multidimensional rehabilitation is an effective intervention for patients with widespread chronic pain. It is a challenge for health politicians to change today's common practice towards that described in evidence-based guidelines. PMID- 17332817 TI - [Rehabilitation of patients with chronic obstructive lung disease]. AB - BACKGROUND: Pulmonary rehabilitation is well established and is increasingly prescribed as part of the treatment for chronic obstructive pulmonary disease (COPD). METHOD: Relevant scientific literature and our own clinical experience is presented. INTERPRETATION: The essential elements of rehabilitation include a multidisciplinary approach; focus on the individual patient; and emphasis on emotional, social, and physical health aspects. The selected patients have COPD symptoms; are fully aware of their physical limitations and motivated to take an active part in the treatment. Pulmonary rehabilitation is also beneficial for patients with other chronic lung diseases A systematic programme includes a detailed clinical examination of the patient, teaching, training in mucus mobilization and breathing techniques, exercise training and psychosocial support. Evidence-based effects of rehabilitation include symptom relief, increased exercise performance, improved quality of life and reduced use of health services. Pulmonary rehabilitation is also necessary before and after lung transplants and in connection with volume reducing surgery for emphysema. PMID- 17332818 TI - [Illness in the Norwegian team during the Olympic winter games 2006 in Torino]. AB - Illness is of major concern for elite level athletes during championships. Much was done to prevent illness in the Norwegian team during the Olympic Winter Games in Torino 2006. Nevertheless, some athletes became ill. This article discusses illness during the Games from both medical and socio-cultural perspectives. Eight athletes in a team of 74 were not able to compete in one or more competitions, while four or five probably competed with reduced levels of performance. Observations have given the impression that efforts to prevent illness and infection may have adversely affected the performers. Athletes and trainers have confirmed this observation. PMID- 17332819 TI - [Routines upon suspicion of driving under influence]. AB - Norway was the first country in the world to introduce an act, in 1936, that prohibits driving with a blood alcohol concentration (BAC) above 0.5 g/kg. This Norwegian Road Traffic Act was expanded in 1959 to include illegal drugs and other medicinal psychoactive drugs. Upon suspicion of drugged driving, a clinical test for impairment (CTI) is performed and blood samples are taken. The Norwegian police have been allowed to request blood analysis for illegal and prescribed drugs affecting driving performance, even by force if drug influence is suspected. There is currently no legal limit for drugs other than alcohol. The Division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Health analyse blood samples from all drivers suspected of drugged driving in Norway. Based on results of the blood sample analysis and the CTI, the DFTDA makes a preliminary conclusion of the probability of impairment comparable to BAC above 0.5 g/kg. Then the prosecuting authority decides whether to charge the suspected driver. The impairment has to be proven to the court in each individual case. The court decision is based on the outcome of the CTI, the blood sample analyses, other information that may be given and in most cases an expert witness statement. The sentences can be conditional or unconditional imprisonment, depending on the BAC or the degree of drug impairment and withdrawal of the driving licence for a period of at least 2 years.. PMID- 17332820 TI - [Heart failure and confidence failure]. PMID- 17332822 TI - [Diuretics not the first-choice-drug in chronic heart failure]. PMID- 17332825 TI - [Is the new St Olav Hospital going to collapse?]. PMID- 17332826 TI - [Problem-free reimbursement changes for COPD]. PMID- 17332830 TI - [Transcendental meditation and health]. PMID- 17332827 TI - [Delivery of the second twin in a circulatory-unstable mother]. PMID- 17332833 TI - [Khat--culture or health problem?]. PMID- 17332836 TI - Relationship between body composition changes and the blood pressure response to exercise test in overweight Japanese subjects. AB - We investigated the link between changes in body composition and the blood pressure (BP) response to exercise in overweight Japanese by a retrospective clinical study carried out over a 3-year period. We analyzed data for 38 overweight Japanese aged 22-69 years (47.8 +- 11.4) at baseline. Among the participants, 32 overweight subjects (body mass index : BMI, 29.0 +- 3.0 kg/m2) were further analyzed with a 3-year follow up. BP at rest, the BP response to an exercise test, the aerobic exercise-level determined ventilatory threshold (VT), and body composition were evaluated at an interval of 1 year. During the study period, there were 6 drop outs, who started to receive anti-hypertensive drugs because of the development of hypertension. Based on analysis of follow up data, parameters of body composition were significantly reduced over the 3 years. Systolic BP (SBP) at rest and at VT was also reduced. In addition, delta SBP (Delta: delta represents positive change in parameters) at VT was positively correlated with Delta parameters of body composition over the 3 years. In overweight subjects with increased body weight, there was a significant time (pre vs year 3) effect and interactions by 2 factor-factorial ANOVA. The present study indicates that changes in body composition are closely linked to the SBP response to an exercise test. PMID- 17332837 TI - Detection of strabismus and amblyopia in 1.5- and 3-year-old children by a preschool vision-screening program in Japan. AB - All children at the age of 1.5 and 3 years in Japan undergo physical, mental, and developmental checkups including dental, eye, and hearing examinations. The vision-screening program consists of 3 steps : questionnaires and home visual acuity testing as the first step (only for 3-year-old children), visual acuity testing by nurses and inspection by medical officers at regional Health Centers as the second step, and detailed examinations by ophthalmologists as the third step. This study aims to reveal the prevalence of strabismus and amblyopia as obtained from data in the vision-screening program. The final diagnoses made by ophthalmologists and sent back to the Health Centers in Okayama City were reviewed to elucidate the prevalence of strabismus, amblyopia, refractive errors, and other diseases in 1.5- and 3-year-old children in Okayama City in 5 years from 2000 to 2004. Of approximately 6,500-6,900 total children, 83.7-86.8% at 1.5 years old and 77.8-81.9% at 3 years old were brought to the Health Centers. The rates of strabismus were 0.01-0.12% at 1.5 years old and 0.20-0.34% at 3 years old, while the rates of amblyopia were 0% at 1.5 years old and 0.13-0.18% at 3 years old. The higher rates of strabismus at 3 years old were attributed mainly to the increase of exotropia and intermittent exotropia. In conclusions, the prevalence of strabismus was different between 1.5- and 3-year-old children. The vision-screening program in Japan functions to detect strabismus and amblyopia. PMID- 17332838 TI - Biochemical characterization of reactive nitrogen species by eosinophil peroxidase in tyrosine nitration. AB - It is well known that eosinophils are involved in tyrosine nitration. In this study, we evaluated tyrosine nitration by rat eosinophils isolated from peritoneal fluid and constituent eosinophils in the stomach. Rat peritoneal eosinophils activated with 1 microM phorbol myristate acetate (PMA) and 50 microM NO2- showed immunostaining for nitrotyrosine only in smaller cells, despite the fact that eosinophils are capable of producing superoxide (O2*-) Free tyrosine nitrating capacity after incubation with PMA and NO2- was 4-fold higher in eosinophils than in neutrophils. Catalase and alpha- and gamma-tocopherol inhibited free tyrosine nitration by reactive nitrogen species from eosinophils but not that by peroxynitrite. Superoxide dismutase augmented free tyrosine nitration by activated eosinophils and peroxynitrite. The concentration of nitric oxide released from eosinophils was relatively low (0.32 microM/10(6) cells/h) and did not contribute to the formation of nitrotyrosine. On the other hand, most constituent eosinophils constituent in the rat stomach stimulated by PMA and NO2- showed tyrosine nitration capacity. These results suggest that intact cells other than apoptotic-like eosinophils eluted in the intraperitoneal cavity could not generate reactive species responsible for nitration by a peroxidase-dependent mechanism. In contrast, normal eosinophils in the stomach were capable of nitration, suggesting that the characteristics of eosinophils in gastric mucosa are different from those eluted in the peritoneal cavity. PMID- 17332839 TI - Comparison of hepatic enzymes between Japanese men with and without metabolic syndrome. AB - We compared the levels of hepatic enzymes in 220 Japanese men with metabolic syndrome with those in age and sex-matched subjects without the syndrome. Metabolic syndrome was defi ned by the new criteria published in Japan, and hepatic enzymes, i.e., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (gammaGTP), were measured. AST, ALT and gammaGTP in subjects with metabolic syndrome were significantly higher than those in subjects without the syndrome, and metabolic syndrome was closely associated with hepatic enzymes in this cohort of Japanese men. PMID- 17332840 TI - A homosexual Japanese man with acute hepatitis due to hepatitis B virus genotype ae, concurrent with amebic colitis. AB - We report herein a case with acute hepatitis due to hepatitis B virus genotype Ae, concurrent with amebic colitis. A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice. Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen. The hepatitis B virus genotype was determined to be Ae. Furthermore, a mud-like stool with blood and mucous had sometimes been noted during the past 3 years, and amebic colitis was shown by colonofiberscopy during hospitalization. The patient was diagnosed with acute hepatitis B, concurrent with amebic colitis, and was successfully treated with lamivudine and metronidazole. In Japanese patients with acute hepatitis B virus genotype A infection, homosexual activity tends to be high. Furthermore, in Japanese homosexual men, amebiasis has been increasing. Thus, in Japanese patients with acute hepatitis B, a determination of genotype should be performed in order to investigate the route of transmission of hepatitis B virus, and a search for amebiasis should be performed in patients with acute hepatitis due to hepatitis B virus genotype A. Furthermore, education of homosexual men regarding hepatitis B virus, hepatitis B virus vaccination, and amebiasis is urgently required. PMID- 17332841 TI - Successful intra-postoperative extracorporeal circulatory support with atrial communication for treatment of anomalous left coronary artery from the pulmonary artery: a case report. AB - We describe a successful case of surgical treatment for anomalous left coronary artery from the pulmonary artery (ALCAPA) syndrome with severe left ventricular dysfunction. Because of the severe left ventricular dysfunction, we planned to use an extracorporeal membrane oxygenation for heart support until a satisfactory recovery had been established. The left ventricular function significantly recovered in a few days, and the patient could be discharged without any complications. PMID- 17332842 TI - Multiple gastrointestinal stromal tumors in neurofibromatosis type 1 treated with laparoscopic surgery. AB - Gastrointestinal stromal tumors (GISTs) have been reported to occasionally occur in patients with neurofibromatosis type 1 (NF-1), and many cases have had multiple lesions predominantly involving the small intestine. We report herein a case of multiple GISTs associated with NF-1 from whom laparoscopic surgery was beneficial. In a 79-year-old female admitted with anemia and melena, the abdominal computed tomography revealed a tumor arising from the small intestine. Laparoscopic surgery was performed, and another small tumor was revealed during laparoscopic observation. Extracorporeal partial and wedge resection of the small intestine were undertaken. Both lesions were diagnosed as typical GISTs of low risk. Laparoscopic surgery would be useful for examination and a minimally invasive approach to tumors of the small intestine, especially on cases with the possibility of multiple tumors. PMID- 17332843 TI - Is the prevalence of overactive bladder overestimated? A population-based study in Finland. AB - BACKGROUND: In earlier studies, one in six adults had overactive bladder which may impair quality of life. However, earlier studies have either not been population-based or have suffered from methodological limitations. Our aim was to assess the prevalence of overactive bladder symptoms, based on a representative study population and using consistent definitions and exclusions. METHODOLOGY/PRINCIPAL FINDINGS: The aim of the study was to assess the age standardized prevalence of overactive bladder defined as urinary urgency, with or without urgency incontinence, usually with urinary frequency and nocturia in the absence of urinary tract infection or other obvious pathology. In 2003-2004, a questionnaire was mailed to 6,000 randomly selected Finns aged 18-79 years who were identified from the Finnish Population Register Centre. Information on voiding symptoms was collected using the validated Danish Prostatic Symptom Score, with additional frequency and nocturia questions. Corrected prevalence was calculated with adjustment for selection bias due to non-response. The questionnaire also elicited co-morbidity and socio-demographic information. Of the 6,000 subjects, 62.4% participated. The prevalence of overactive bladder was 6.5% (95% CI, 5.5% to 7.6%) for men and 9.3% (CI, 7.9% to 10.6%) for women. Exclusion of men with benign prostatic hyperplasia reduced prevalence among men by approximately one percentage point (to 5.6% [CI, 4.5% to 6.6%]). Among subjects with overactive bladder, urgency incontinence, frequency, and nocturia were reported by 11%, 23%, and 56% of men and 27%, 38%, and 40% of women, respectively. However, only 31% of men and 35% of women with frequency, and 31% of subjects of both sexes with nocturia reported overactive bladder. CONCLUSIONS/SIGNIFICANCE: Our results indicate a prevalence of overactive bladder as low as 8% suggesting that, in previous studies, occurrence has been overestimated due to vague criteria and selected study populations regarding age distribution and low participation. PMID- 17332844 TI - Percutaneous exposure incidents of the health care personnel in a newly founded tertiary hospital: a prospective study. AB - BACKGROUND: Percutaneous exposure incidents (PEIs) and blood splashes on the skin of health care workers are a major concern, since they expose susceptible employees to the risk of infectious diseases. We undertook this study in order to estimate the overall incidence of such injuries in a newly founded tertiary hospital, and to evaluate possible changes in their incidence over time. METHODOLOGY/PRINCIPAL FINDINGS: We prospectively studied the PEIs and blood splashes on the skin of employees in a newly founded (October 2000) tertiary hospital in Athens, Greece, while a vaccination program against hepatitis B virus, as well as educational activities for avoidance of injuries, were taking place. The study period ranged from October 1, 2002 to February 28, 2005. Serologic studies for hepatitis B (HBV) and C virus (HCV) as well as human immunodeficiency virus (HIV) were performed in all injured employees and the source patients, when known. High-titer immunoglobulin (250 IU anti-HBs intramuscularly) and HBV vaccination were given to non-vaccinated or previously vaccinated but serologically non-responders after exposure. Statistical analysis of the data was performed using Mc Nemar's and Fisher's tests. 60 needlestick, 11 sharp injuries, and two splashes leading to exposure of the skin or mucosa to blood were reported during the study period in 71 nurses and two members of the cleaning staff. The overall incidence (percutaneous injuries and splashes) per 100 full-time employment-years (100 FTEYs) for high-risk personnel (nursing, medical, and cleaning staff) was 3.48, whereas the incidence of percutaneous injuries (needlestick and sharp injuries) alone per 100 FTEYs was 3.38. A higher incidence of injuries was noted during the first than in the second half of the study period (4.67 versus 2.29 per 100 FTEYs, p = 0.005). No source patient was found positive for HCV or HIV. The use of high-titer immunoglobulin after adjustment for the incidence of injuries was higher in the first than in the second half of the study period, although the difference was not statistically significant [9/49 (18.37%) vs 1/24 (4.17%), p = 0.15]. CONCLUSIONS/SIGNIFICANCE: Our data show that nurses are the healthcare worker group that reports most of PEIs. Doctors did not report such injuries during the study period in our setting. However, the possibility of even relatively frequent PEIs in doctors cannot be excluded. This is due to underreporting of such events that has been previously described for physicians and surgeons. A decrease of the incidence of PEIs occurred during the operation of this newly founded hospital. PMID- 17332846 TI - Kiwi forego vision in the guidance of their nocturnal activities. AB - BACKGROUND: In vision, there is a trade-off between sensitivity and resolution, and any eye which maximises information gain at low light levels needs to be large. This imposes exacting constraints upon vision in nocturnal flying birds. Eyes are essentially heavy, fluid-filled chambers, and in flying birds their increased size is countered by selection for both reduced body mass and the distribution of mass towards the body core. Freed from these mass constraints, it would be predicted that in flightless birds nocturnality should favour the evolution of large eyes and reliance upon visual cues for the guidance of activity. METHODOLOGY/PRINCIPAL FINDINGS: We show that in Kiwi (Apterygidae), flightlessness and nocturnality have, in fact, resulted in the opposite outcome. Kiwi show minimal reliance upon vision indicated by eye structure, visual field topography, and brain structures, and increased reliance upon tactile and olfactory information. CONCLUSIONS/SIGNIFICANCE: This lack of reliance upon vision and increased reliance upon tactile and olfactory information in Kiwi is markedly similar to the situation in nocturnal mammals that exploit the forest floor. That Kiwi and mammals evolved to exploit these habitats quite independently provides evidence for convergent evolution in their sensory capacities that are tuned to a common set of perceptual challenges found in forest floor habitats at night and which cannot be met by the vertebrate visual system. We propose that the Kiwi visual system has undergone adaptive regressive evolution driven by the trade-off between the relatively low rate of gain of visual information that is possible at low light levels, and the metabolic costs of extracting that information. PMID- 17332845 TI - Meta-analysis in genome-wide association datasets: strategies and application in Parkinson disease. AB - BACKGROUND: Genome-wide association studies hold substantial promise for identifying common genetic variants that regulate susceptibility to complex diseases. However, for the detection of small genetic effects, single studies may be underpowered. Power may be improved by combining genome-wide datasets with meta-analytic techniques. METHODOLOGY/PRINCIPAL FINDINGS: Both single and two stage genome-wide data may be combined and there are several possible strategies. In the two-stage framework, we considered the options of (1) enhancement of replication data and (2) enhancement of first-stage data, and then, we also considered (3) joint meta-analyses including all first-stage and second-stage data. These strategies were examined empirically using data from two genome-wide association studies (three datasets) on Parkinson disease. In the three strategies, we derived 12, 5, and 49 single nucleotide polymorphisms that show significant associations at conventional levels of statistical significance. None of these remained significant after conservative adjustment for the number of performed analyses in each strategy. However, some may warrant further consideration: 6 SNPs were identified with at least 2 of the 3 strategies and 3 SNPs [rs1000291 on chromosome 3, rs2241743 on chromosome 4 and rs3018626 on chromosome 11] were identified with all 3 strategies and had no or minimal between-dataset heterogeneity (I(2) = 0, 0 and 15%, respectively). Analyses were primarily limited by the suboptimal overlap of tested polymorphisms across different datasets (e.g., only 31,192 shared polymorphisms between the two tier 1 datasets). CONCLUSIONS/SIGNIFICANCE: Meta-analysis may be used to improve the power and examine the between-dataset heterogeneity of genome-wide association studies. Prospective designs may be most efficient, if they try to maximize the overlap of genotyping platforms and anticipate the combination of data across many genome-wide association studies. PMID- 17332847 TI - Artificially introduced aneuploid chromosomes assume a conserved position in colon cancer cells. AB - BACKGROUND: Chromosomal aneuploidy is a defining feature of carcinomas. For instance, in colon cancer, an additional copy of Chromosome 7 is not only observed in early pre-malignant polyps, but is faithfully maintained throughout progression to metastasis. These copy number changes show a positive correlation with average transcript levels of resident genes. An independent line of research has also established that specific chromosomes occupy a well conserved 3D position within the interphase nucleus. METHODOLOGY/PRINCIPAL FINDINGS: We investigated whether cancer-specific aneuploid chromosomes assume a 3D-position similar to that of its endogenous homologues, which would suggest a possible correlation with transcriptional activity. Using 3D-FISH and confocal laser scanning microscopy, we show that Chromosomes 7, 18, or 19 introduced via microcell-mediated chromosome transfer into the parental diploid colon cancer cell line DLD-1 maintain their conserved position in the interphase nucleus. CONCLUSIONS: Our data is therefore consistent with the model that each chromosome has an associated zip code (possibly gene density) that determines its nuclear localization. Whether the nuclear localization determines or is determined by the transcriptional activity of resident genes has yet to be ascertained. PMID- 17332848 TI - Fear of losing money? Aversive conditioning with secondary reinforcers. AB - Money is a secondary reinforcer that acquires its value through social communication and interaction. In everyday human behavior and laboratory studies, money has been shown to influence appetitive or reward learning. It is unclear, however, if money has a similar impact on aversive learning. The goal of this study was to investigate the efficacy of money in aversive learning, comparing it with primary reinforcers that are traditionally used in fear conditioning paradigms. A series of experiments were conducted in which participants initially played a gambling game that led to a monetary gain. They were then presented with an aversive conditioning paradigm, with either shock (primary reinforcer) or loss of money (secondary reinforcer) as the unconditioned stimulus. Skin conductance responses and subjective ratings indicated that potential monetary loss modulated the conditioned response. Depending on the presentation context, the secondary reinforcer was as effective as the primary reinforcer during aversive conditioning. These results suggest that stimuli that acquire reinforcing properties through social communication and interaction, such as money, can effectively influence aversive learning. PMID- 17332849 TI - Quality of life in HIV clinical trials: why sexual health must not be ignored. PMID- 17332850 TI - The case for cultural competence in health professions education. AB - Health profession schools in the United States have to be able to meet the health and pharmaceutical care demands of a rapidly growing racial and multiethnic population. One tactic is to develop and implement or expand existing resources and didactic courses to address cultural competence in the curricula of every college and school of pharmacy. The curriculum should require a focus on the reality of evidence-based health disparities among racial and ethnic minority populations; importance of providing culturally competent care and communication to meet the health needs of diverse patient populations; and exposure to cultural diversity. Students should be grounded in cultural awareness and cultural sensitivity. This article establishes a case for integrating cultural competence into the curricula of health professions schools. PMID- 17332851 TI - A required course in human genomics, pharmacogenomics, and bioinformatics. AB - OBJECTIVES: To provide students with an understanding of the principles and applications of human genetics and genomics in drug therapy optimization, patient care, and counseling. DESIGN: A 2-credit hour course entitled Principles of the Human Genome, Pharmacogenomics, and Bioinformatics was offered to third professional year PharmD students. Written examinations, in-class exercises, and a written paper evaluating the current literature were used to evaluate student learning. ASSESSMENT: Student course ratings on the pedagogical format of the course and the relevance of course material to professional practice have improved significantly since first implementation in 2002. CONCLUSION: This course provided pharmacy students with an understanding of pharmacogenetics ranging from genetic principles and the inheritance of complex traits to specific examples of pharmacogenomics in drug therapy. PMID- 17332852 TI - Student perceptions of online lectures and WebCT in an introductory drug information course. AB - OBJECTIVES: To determine student perceptions regarding online lectures and quizzes during an introductory drug information course for first-year professional doctor of pharmacy students. DESIGN: Formal and online lectures, online quizzes, written semester projects, a practice-based examination, a careers in pharmacy exercise, and a final examination were used to deliver the course content and assess performance. A multiple-choice survey instrument was used to evaluate student perceptions of WebCT and online lectures. ASSESSMENT: More than 47% of students reported that online lectures helped them learn the material better, 77% reported that lectures would be used to study for the final examination, and 59% reported that they would use WebCT lectures for future classes. Approximately 40% of students agreed that online lectures should be used in future courses. CONCLUSION: Students reported that WebCT was easy to use; however, the majority of students preferred in-class lectures compared to online lectures. A positive correlation was observed for those students who performed well on the online quizzes and those who performed well on the final examination. PMID- 17332853 TI - Weekly rotation of facilitators to improve assessment of group participation in a problem-based learning curriculum. AB - OBJECTIVES: To determine whether implementing a rotating facilitator structure provides a reliable method of assessing group participation and assigning grades to third-professional year pharmacy students in a problem-based learning curriculum. DESIGN: In the 2004-2005 school year, a "one block, one facilitator" structure was replaced by a "weekly rotating facilitator" structure. Each student received a grade from the assigned facilitator each week. The 8 weekly grades were then averaged for a final course grade. Student grades were reviewed weekly and at the end of each block. Facilitators and students completed survey instruments at the end of each of four 8-week blocks. ASSESSMENT: Student grades were reviewed, and the class average was compared to the class averages from the 2 previous years. For example, in block I the class average was 86 which compared to averages of 88 and 87 for 2002-03 and 2003-04 respectively. Survey data revealed a 40% agreement by facilitators in block I that student performance was improved compared to student performance prior to this change. This agreement increased to 71%, 72%, and 71% respectively for blocks II - IV. Student survey data at the end of the academic year supported weekly facilitator rotation and revealed that a majority of students agreed that exposure to a variety of facilitators enhanced their group participation. CONCLUSION: As confirmed by student grades and student and faculty members' feedback, the change to a rotating facilitator structure resulted in a reliable method of assigning student grades for group participation. PMID- 17332854 TI - The predictive utility of nontraditional test scores for first-year pharmacy student academic performance. AB - OBJECTIVES: To determine the value of employing the Learning and Study Strategies Inventory (LASSI), Defining Issues Test (DIT), and Watson-Glaser Critical Thinking Appraisal (WGCTA) in predictive models for first-year pharmacy student academic performance. METHODS: Six years of pharmacy student admission and progression data were evaluated. Additional predictive validity offered by these variables over a model of prepharmacy grade point average and pharmacy college admission test (PCAT) score was examined. RESULTS: None of the 3 measures offered the ability to predict first-semester or first-year academic performance over and above GPA and PCAT. CONCLUSIONS: The LASSI, DIT, and WGCTA do not appear to assess abilities that are directly related to academic performance; however, these instruments may be useful in assessing other student attributes that are highly desirable for the practice of pharmacy. PMID- 17332855 TI - Attitudes towards complementary and alternative medicine among pharmacy faculty and students. AB - OBJECTIVES: To determine pharmacy faculty members' and students' attitudes and perceptions regarding the use of complementary and alternative medicine (CAM). METHODS: A survey was used to obtain data on the following information concerning CAM: general attitudes, perceived barriers to use, training received and desired, personal use, and information sources used. RESULTS: In general, attitudes of pharmacy faculty members and students towards CAM were positive. Lack of evidence for CAM practices was considered the greatest barrier to the use of CAM by faculty members and students. Many CAM therapies were perceived to be effective. A high percentage of students desire more training in the areas of herbal medicine and nutritional supplements. Faculty members and students believe that CAM should be included in the curriculum. CONCLUSIONS: General attitudes towards CAM are positive among pharmacy faculty members and students, and most believe that CAM should be taught in the pharmacy curriculum. More resources and training of faculty members may be necessary. PMID- 17332856 TI - Geriatric content in pharmacotherapy and therapeutics textbooks. AB - OBJECTIVES: To determine the extent to which therapeutics textbooks address age related medication information. METHODS: Criteria for 5 disease states prevalent among geriatric patients were developed based on the content of a geriatric textbook and from expert reviewers' input. The criteria were used to determine the degree to which geriatric content was addressed in 3 therapeutics textbooks. RESULTS: The therapeutics textbooks contained less than half of the critical points for 3 disease states: chronic obstructive pulmonary disease, heart failure, and diabetes mellitus (31%, 33%, and 46%, respectively). In addition, the textbooks addressed only one half to two thirds of the criteria for the remaining 2 disease states of osteoarthritis and dementia (55% and 68%, respectively). Criteria specific to the elderly were addressed less often than criteria that were important but not unique to the elderly (38% and 63%, respectively). CONCLUSIONS: Current therapeutics textbooks have significant gaps in geriatric medication information. Users of these textbooks must supplement them with primary literature or a geriatric textbook for more comprehensive medication therapy management information. PMID- 17332857 TI - "Testwiseness" among international pharmacy graduates and Canadian senior pharmacy students. AB - OBJECTIVE: To compare the test-taking skills and abilities (testwiseness) of Canadian senior-level pharmacy students with those of international pharmacy graduates. METHODS: A 20-item testwiseness questionnaire was developed and administered to 102 participants: 35 senior-level pharmacy students, 34 international pharmacy graduates, and 34 practicing pharmacists who served as a control group. RESULTS: Mean testwiseness scores indicated significant differences in performance between senior-level pharmacy students and international pharmacy graduates. Testwiseness deficiencies of international pharmacy graduates were particularly severe in domains requiring discerning use of English language. CONCLUSIONS: Differences in testwiseness appear to exist between Canadian senior-level pharmacy students and international pharmacy graduates. The genesis and implications of these differences must be evaluated further in order to determine whether testwiseness affects learning, professional development, or clinical practice. PMID- 17332858 TI - Retention of compounding skills among pharmacy students. AB - OBJECTIVE: To evaluate the competency of second-year pharmacy students to compound capsules from a prescription 12 months after completing a compounding course. METHODS: Students who completed the compounding course were given the same prescription they had been given 12 months earlier to compound metoprolol capsules. No warning of the second exercise was given and they were expected to prepare capsules and package and label the finished product. Performance was evaluated in an identical manner for both exercises based on the level of professional competency of a score of 80% or above. RESULTS: Eighty-seven percent fewer students achieved a score of 90% or more on the second exercise and 81% fewer students demonstrated the required competency. CONCLUSIONS: Differences in scores on the first and second exercises indicate that pharmacy students' level of competency and retention of knowledge with respect to compounding capsules is not adequately retained after a 12-month hiatus. PMID- 17332859 TI - Development and implementation of a scoring rubric for aseptic technique. AB - OBJECTIVE: To assess students' development of aseptic technique skills through the use of a scoring rubric. DESIGN: A scoring rubric was developed to assess students in 6 skill areas of parenteral preparation. Areas were assessed as "likely harmful," "needs improvement," or "acceptable" according to developed criteria. Students were assessed at baseline and at the end of the fall and spring semesters. ASSESSMENT: Of 624 ratings given to 104 students at baseline and at the end of the spring semester, respectively, 51.1% and 88.9% were "acceptable," 17.9% and 7.6% were "needs improvement," and 30.9% and 3.5% were "likely harmful" (p < 0.001 vs baseline). The percentage of students receiving one or more likely harmful ratings decreased from 85.6% at baseline to 18.3% (p < 0.001). CONCLUSION: Use of the rubric successfully documented student improvement. It also identified areas that need additional emphasis in the curriculum. PMID- 17332860 TI - Instrumentation for comparing student and faculty perceptions of competency-based assessment. AB - OBJECTIVES: To compare student and faculty perceptions of the delivery and achievement of professional competencies in a doctor of pharmacy program in order to provide data for both accountability and curricular improvement purposes. DESIGN: A survey instrument was designed based on current learning theory, and 76 specific competency statements generated from mission and goal statements of The Ohio State University College of Pharmacy and the Center for the Advancement of Pharmaceutical Education. This instrument was administered to PharmD program students and faculty. ASSESSMENT: The number of competencies by program year that are delivered in the curriculum, the percent of students and faculty reporting individual competency delivery and achievement, and differences between student and faculty perceptions of competency delivery and achievement are reported. CONCLUSION: The faculty and student opinions provided an in-depth view of curricular outcomes. Gathering perception data from faculty and students about the delivery and achievement of competencies in a PharmD program can be used to both meet accreditation requirements (accountability) and to improve the curriculum (improvement). PMID- 17332861 TI - Backward course design: making the end the beginning. PMID- 17332863 TI - Nonprescription drug therapy: issues and opportunities. AB - Nonprescription drug therapy is tightly woven into the fabric of American health care. Market forces are expected to contribute to significant expansion of nonprescription drug use. Consumers place high value on nonprescription drug therapy; however, self-medicating patients frequently need assistance from a learned intermediary to assure optimal integration of nonprescription drug therapy into the total care regimen. Pharmacist-assisted self-care holds vast potential to serve the public interest, but this expanded practice role will require higher levels of professional practice commitment by American pharmacy. That commitment must be supported by practice-relevant, competency-based, patient centered college and school of pharmacy curricula and continuing education that assures perpetual intellectual proficiency in nonprescription drug pharmacotherapy. That knowledge and competency must be integrated holistically into the total mix of patient comorbidity and polypharmacy. The pharmacist assisted self-care business and professional practice model must be further facilitated by state and national pharmacy organizations, chain and independent community pharmacy, pharmacy wholesalers, and others. Consumers await expanded and differentiated pharmacy-based, pharmacist-provided medication therapy management services focused on the safe, appropriate, and effective selection, use, and monitoring of nonprescription drugs therapy. PMID- 17332864 TI - Nonpresciption medicines and the North American Pharmacist Licensure Examination. AB - The North American Pharmacist Licensure Examination (NAPLEX) is currently used by all 50 state boards of pharmacy to aid in determining whether a candidate for licensure possesses the minimal knowledge and skills required to safely and effectively practice pharmacy. The blueprint for this examination periodically undergoes revision so that it remains current with the demands and trends of modern-day pharmacy practice. During the most recent revision, which occurred between 2002 and 2004, several substantial content changes were incorporated. One of the most notable changes was the elimination of any distinction of importance between prescription and nonprescription medications. This change was in response to several factors, including the growing variety of conditions for which nonprescription medications are available and the recent switching of several pharmaceutical products from prescription-only to nonprescription status. The previous example is indicative of how the practice of pharmacy is continually evolving and the need for periodic changes to the examination used in the licensure process. As such, the NAPLEX blueprint is continually reviewed and revised to ensure it includes the most current knowledge and skills required of entry-level practitioners. PMID- 17332865 TI - Status and recommendations for self-care instruction in US colleges and schools of pharmacy, 2006. AB - Teachers of pharmacy self-care courses have met annually since 1998 at the Nonprescription Medicines Academy (NMA) held in Cincinnati, Ohio. During these meetings, self-care faculty members discuss methods of enhancing the teaching of self-care in US colleges and schools of pharmacy. Self-care courses are taught using a variety of methods and content is woven into pharmacy curricula in many different ways. This manuscript sets forth the current state of self-care instruction in pharmacy curricula including the recommended core curriculum, instructional methodologies, course mechanics, existing standards, and assessment and curricular placement, and makes recommendations for the future. PMID- 17332866 TI - Constructing a self-care curriculum. AB - The purpose of this paper is to describe the unique challenges presented by a dynamic marketplace when designing a self-care curriculum. As manufacturers seek to satisfy consumer demand and increase market product shares, rapid changes occur with brand name extensions and prescription to nonprescription switches. The US Food and Drug Administration's continuous process of approving ingredients (monographs) add to this changing environment. Thus, developing learning outcomes beyond drug knowledge becomes critical. Learning outcomes must also address the multifaceted nature of self-care, including the development of skills in patient assessment (triage) and education. Determining which content areas to be covered can be difficult when consumer demand and marketplace changes are considered. For example, consumer use of dietary and herbal supplements forces pharmacists to have some basic knowledge of safety and efficacy regarding these products. Ultimately, given the dynamic, multifaceted nature of self-care, developing life long learning skills/attitudes in students may be the most important outcome necessary for a self-care curriculum. PMID- 17332867 TI - Ethical, scientific, and educational concerns with unproven medications. AB - Quackery (promotion of products that do not work or have not been proven to work) was once a commonly used term within the pharmacy and medical communities. However, an increasingly anti-scientific national climate culminated in passage of the 1994 Dietary Supplement Health and Education Act, which granted unprecedented legitimacy to "dietary supplements" that had not been scientifically proven to be effective and/or safe. In part, this was facilitated when professional pharmacy magazines and journals published advertisements and articles promoting these unproven medications. Gradually, pharmacy codes of ethics eliminated references to quackery, and some pharmacy organizations seemed to accept the unproven medications they once exhorted the pharmacist not to sell. The profession's shift in attitude toward unproven medications occurred as the medical community at large began to realize the value of evidence-based medicine. Academicians must resist pressure to present unproven therapies as realistic alternatives for medications with scientific proof of safety and efficacy. They must stress the value of evidence-based medicine and urge students and pharmacists to recommend only those medications with evidence-based proof of safety and efficacy. PMID- 17332868 TI - Teaching self-care as a junior faculty member: perspectives and lessons learned. AB - Self-care is an important component of the doctor of pharmacy curriculum due to the expanding nonprescription medication market and the high percentage of pharmacists practicing in community pharmacy. It can be incorporated as a freestanding course or integrated throughout the curriculum. This article presents the experiences of 2 junior faculty members at 2 different pharmacy schools who were charged with coordinating self-care instruction at their institutions. It discusses the "lessons learned" regarding teaching self-care effectively in an integrated curriculum and in a freestanding course. PMID- 17332869 TI - Engaging students in self-care activities during an advanced community pharmacy practice experience. AB - OBJECTIVE: To provide experiential rotation students with educational activities to enhance learning and patient communication skills with respect to nonprescription drug therapy. DESIGN: A longitudinal project, a consultation guide, and a list of mini-projects were developed for a 4-week community pharmacy rotation experience. The longitudinal project was a nonprescription pocket formulary consisting of 4 disease states and their respective treatment options. The consultation guide was a 1-page data collection form intended to capture patient information regarding the use of nonprescription products in a thorough and brief manner. The mini-projects were questions to be answered while spending time in the nonprescription medication aisles. ASSESSMENT: Students were very creative in developing their formularies. They also became more familiar with using nonprescription product references and package labeling information. The consultation guide taught students to apply the "PQRSTA" mnemonic. It prompted discussion of self-care issues and served as a useful educational tool for the preceptor. The list of mini-projects forced students to become familiar with the many nonprescription products available, as well as product line extensions and duplication. CONCLUSION: Students were able to apply and build upon what was learned during their didactic education. The activities provided an excellent means of enhancing patient counseling and problem-solving skills. Additionally, the preceptor relied on these activities to engage students in conversation pertaining to nonprescription products and self-care related issues. PMID- 17332870 TI - Integrating an elective self-care experience with a required advanced pharmacy practice community experience. AB - The development, planning, implementation, and integration of a nonprescription medication (self-care) experience into an existing community advanced pharmacy practice experience (APPE) at the University of Arkansas for Medical Sciences College of Pharmacy is described. The APPE will provide enhanced self-care education and skill development for students in response to the new Accreditation Council for Pharmacy Education Standards and Guidelines for the Professional Program in Pharmacy Leading to the Doctor of Pharmacy Degree, which will take effect in July 2007. A description of the Advanced Community Pharmacy Over-The Counter APPE is provided along with insights gleaned from the faculty involved. PMID- 17332872 TI - Encouraging pharmacy students to become agents of change in health care. PMID- 17332873 TI - Administrative retreats: a new twist to avoid "administrative isolation". PMID- 17332875 TI - A new JCI conflict-of-interest policy. AB - As stewards of the JCI, we are responsible for instituting and sustaining the highest possible standards for integrity. To this end, we have established a very specific set of guidelines for handling potential conflicts of interest - not only for authors and referees, but also for ourselves. PMID- 17332876 TI - Halfway there: the struggle to manage conflicts of interest. AB - Conflicts of interest are known to create problems for the integrity of biomedical research. The editors of the JCI have set out a rigorous policy to help manage conflicts. But they focus only on financially generated conflicts. Here I identify other sources of conflict and offer some suggestions for their management. PMID- 17332877 TI - Stem cells are on the House. PMID- 17332878 TI - The fundamental basis of inflammatory bowel disease. AB - Two broad hypotheses have arisen regarding the fundamental nature of the pathogenesis of inflammatory bowel diseases (IBDs, which include ulcerative colitis and Crohn disease). The first contends that primary dysregulation of the mucosal immune system leads to excessive immunologic responses to normal microflora. The second suggests that changes in the composition of gut microflora and/or deranged epithelial barrier function elicits pathologic responses from the normal mucosal immune system. Here we examine these hypotheses and conclude that IBD is indeed characterized by an abnormal mucosal immune response but that microbial factors and epithelial cell abnormalities can facilitate this response. PMID- 17332879 TI - Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. AB - Fibroproliferative diseases, including the pulmonary fibroses, systemic sclerosis, liver cirrhosis, cardiovascular disease, progressive kidney disease, and macular degeneration, are a leading cause of morbidity and mortality and can affect all tissues and organ systems. Fibrotic tissue remodeling can also influence cancer metastasis and accelerate chronic graft rejection in transplant recipients. Nevertheless, despite its enormous impact on human health, there are currently no approved treatments that directly target the mechanism(s) of fibrosis. The primary goals of this Review series on fibrotic diseases are to discuss some of the major fibroproliferative diseases and to identify the common and unique mechanisms of fibrogenesis that might be exploited in the development of effective antifibrotic therapies. PMID- 17332880 TI - Infectious disease, the innate immune response, and fibrosis. AB - The unrelenting and destructive progression of most fibrotic responses in the pulmonary, cardiovascular, integumentary, and alimentary systems remains a major medical challenge for which therapies are desperately needed. The pathophysiology of fibrosis remains an enigma, but considerable research and debate surrounds the question of whether chronic inflammation is the key driver of unrestrained wound healing (i.e., the fibrotic response) in these and other organ systems. This Review describes how infectious pathogens, chronic inflammation, and unrestrained fibroproliferation are likely to be part of a dynamic, unrelenting process propelling human fibrotic diseases. PMID- 17332881 TI - Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. AB - Models of liver fibrosis, which include cell culture models, explanted and biopsied human material, and experimental animal models, have demonstrated that liver fibrosis is a highly dynamic example of solid organ wound healing. Recent work in human and animal models has shown that liver fibrosis is potentially reversible and, in specific circumstances, demonstrates resolution with a restoration of near normal architecture. This Review highlights the manner in which studies of models of liver fibrosis have contributed to the paradigm of dynamic wound healing in this solid organ. PMID- 17332882 TI - The role of CXC chemokines in pulmonary fibrosis. AB - The CXC chemokine family is a pleiotropic family of cytokines that are involved in promoting the trafficking of various leukocytes, in regulating angiogenesis and vascular remodeling, and in promoting the mobilization and trafficking of mesenchymal progenitor cells such as fibrocytes. These functions of CXC chemokines are important in the pathogenesis of pulmonary fibrosis and other fibroproliferative disorders. In this Review, we discuss the biology of CXC chemokine family members, specifically as it relates to their role in regulating vascular remodeling and trafficking of circulating mesenchymal progenitor cells (also known as fibrocytes) in pulmonary fibrosis. PMID- 17332883 TI - Systemic sclerosis: a prototypic multisystem fibrotic disorder. AB - A unique feature of systemic sclerosis (SSc) that distinguishes it from other fibrotic disorders is that autoimmunity and vasculopathy characteristically precede fibrosis. Moreover, fibrosis in SSc is not restricted to a single organ, but rather affects many organs and accounts for much of the morbidity and mortality associated with this disease. Although immunomodulatory drugs have been used extensively in the treatment of SSc, no therapy to date has been able to reverse or slow the progression of tissue fibrosis or substantially modify the natural progression of the disease. In this Review, we highlight recent studies that shed light on the cellular and molecular mechanisms underlying the fibrotic process in SSc and that identify cellular processes and intra- and extracellular proteins as potential novel targets for therapy in this prototypic multisystemic fibrotic disease. PMID- 17332884 TI - ECM remodeling in hypertensive heart disease. AB - Hypertensive heart disease (HHD) occurs in patients that clinically have both diastolic and systolic heart failure and will soon become the most common cause of heart failure. Two key aspects of heart failure secondary to HHD are the relatively highly prevalent LV hypertrophy and cardiac fibrosis, caused by changes in the local and systemic neurohormonal environment. The fibrotic state is marked by changes in the balance between MMPs and their inhibitors, which alter the composition of the ECM. Importantly, the fibrotic ECM impairs cardiomyocyte function. Recent research suggests that therapies targeting the expression, synthesis, or activation of the enzymes responsible for ECM homeostasis might represent novel opportunities to modify the natural progression of HHD. PMID- 17332886 TI - Mutations in coenzyme Q10 biosynthetic genes. AB - Although it was first described in 1989, our understanding of coenzyme Q10 (CoQ10) deficiency is only now coming of age with the recent first description of the underlying molecular defects. The diverse clinical presentations, classifiable into four major syndromes, raise the question as to whether the deficiencies are primary or secondary. Recent studies, including the one by Mollet, Rotig, and colleagues reported in this issue of the JCI, document molecular defects in three of the nine genes required for CoQ10 biosynthesis, all of which are associated with early and severe clinical presentations (see the related article beginning on page 765). It is anticipated that defects in the other six genes will cause similar early-onset encephalomyopathies. Awareness of CoQ10 deficiency is important because individuals with primary or secondary variants may benefit from oral CoQ10 supplementation. PMID- 17332885 TI - Fibrosis and diseases of the eye. AB - Most diseases that cause catastrophic loss of vision do so as a result of abnormal angiogenesis and wound healing, often in response to tissue ischemia or inflammation. Disruption of the highly ordered tissue architecture in the eye caused by vascular leakage, hemorrhage, and concomitant fibrosis can lead to mechanical disruption of the visual axis and/or biological malfunctioning. An increased understanding of inflammation, wound healing, and angiogenesis has led to the development of drugs effective in modulating these biological processes and, in certain circumstances, the preservation of vision. Unfortunately, such pharmacological interventions often are too little, too late, and progression of vision loss frequently occurs. The recent development of progenitor and/or stem cell technologies holds promise for the treatment of currently incurable ocular diseases. PMID- 17332887 TI - CHIP-ping away at tau. AB - Protein accumulation is a hallmark of many neurodegenerative disorders. In Alzheimer's disease (AD), a hyperphosphorylated form of the protein tau (p-tau) forms intracellular inclusions known as neurofibrillary tangles. Deposits of p tau have also been found in the brains of patients with Down's syndrome, supranuclear palsy, and prion disease. Mutations in tau have been causally associated with at least one inherited neurologic disorder, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), implying that tau abnormalities by themselves can be a primary cause of degenerative diseases of the CNS. Removal of these p-tau species may occur by both chaperone-mediated refolding and degradation. In this issue of the JCI, Dickey and colleagues show that a cochaperone protein, carboxyl terminus of Hsp70-interacting protein (CHIP), in a complex with Hsp90 plays an important role in the removal of p-tau (see the related article beginning on page 648). Pharmacologic manipulation of Hsp90 may be used to alleviate p-tau accumulation in disease. PMID- 17332888 TI - Salt, sodium channels, and SGK1. AB - The hormone aldosterone increases extracellular fluid volume and blood pressure by activating epithelial Na+ channels (ENaCs). Serum- and glucocorticoid-induced kinase 1 (SGK1) is an aldosterone-stimulated signaling molecule that enhances distal nephron Na+ transport, in part by preventing the internalization of ENaCs from the plasma membrane. In this issue of the JCI, Zhang et al. demonstrate that SGK1 enhances transcription of the alpha subunit of ENaC by preventing histone methylation, providing an additional mechanism by which SGK1 increases ENaC mediated Na+ transport in the distal nephron (see the related article beginning on page 773). PMID- 17332889 TI - HDL proteomics: pot of gold or Pandora's box? AB - In this issue of the JCI, Vaisar et al. studied the proteome of HDL (see the related article beginning on page 746). They reveal, quite unexpectedly, that HDL is enriched in several proteins involved in the complement cascade, as well as in a variety of protease inhibitors, supporting the concept that HDL plays a role in innate immunity and in the regulation of proteolytic cascades involved in inflammatory and coagulation processes. The protein makeup of HDL also appears to be altered in patients with coronary artery disease. HDL proteomics is in its infancy, and preliminary findings will need to be confirmed using standardized approaches in larger clinical samples. However, this approach promises to better elucidate the relationship of HDL to atherosclerosis and its complications and could eventually help in the development of biomarkers to predict the outcome of interventions that alter HDL levels and functions. PMID- 17332890 TI - Autoantibody selection and production in early human life. AB - Natural antibodies are autoreactive/polyreactive antibodies believed to be secreted in the absence of xenoantigens. The origin and functional role of this limited and selective autoimmunity are not clear, nor is the specificity and range of autoantigens that drive the development of B cells producing natural antibodies. In this issue of the JCI, Merbl et al. report that in utero, humans generate natural IgM and IgA antibodies that recognize a uniform set of autoantigens (see the related article beginning on page 712), some of which are associated with autoimmune diseases. The authors postulate that this "autoimmunity" at birth favors the emergence of autoimmune diseases in later life. We present a molecular basis for the limited and common repertoire of antibodies produced by fetal B cells, which may be distinct from the abnormalities in B cell development described in patients with autoimmune diseases. PMID- 17332891 TI - Scavenger receptors clear the air. AB - Inhaled environmental oxidants, such as ozone and particulates, have been variably linked to epithelial injury, inflammation, and perturbations in lung development, growth, and function. Reactions between ozone and lung surface lipids likely account for exposure-related pathophysiologic sequelae. In this issue of the JCI, Dahl et al. document a previously unrecognized pulmonary defense against inhaled oxidants in mice: macrophage scavenger receptors (SRs) bind proinflammatory oxidized lipids, thereby decreasing pulmonary inflammation (see the related article beginning on page 757). The study adds to our knowledge of diverse lung oxidative processes and identifies a potential regulatory mechanism governing pulmonary inflammation. Further investigations to elucidate more precise mechanisms and to determine the influence of SRs on airway epithelial injury, repair, and remodeling are warranted. PMID- 17332892 TI - Newborn humans manifest autoantibodies to defined self molecules detected by antigen microarray informatics. AB - Autoimmune diseases are often marked by autoantibodies binding to self antigens. However, many healthy persons also manifest autoantibodies that bind to self antigens, known as natural autoantibodies. In order to characterize natural autoantibodies present at birth, we used an antigen microarray (antigen chip) to analyze informatically (with clustering algorithms and correlation mapping) the natural IgM, IgA, and IgG autoantibody repertoires present in 10 pairs of sera from healthy mothers and the cords of their newborn babies. These autoantibodies were found to bind to 305 different, mostly self, molecules. We report that in utero, humans develop IgM and IgA autoantibodies to relatively uniform sets of self molecules. The global patterns of maternal IgM autoantibodies significantly diverged from those at birth, although certain reactivities remained common to both maternal and cord samples. Because maternal IgG antibodies (unlike IgM and IgA) cross the placenta, maternal and cord IgG autoantibodies showed essentially identical reactivities. We found that some self antigens that bind cord autoantibodies were among the target self antigens associated with autoimmune diseases later in life. Thus, the obviously benign autoimmunity prevalent at birth may provide the basis for the emergence of some autoimmune diseases relatively prevalent later in life. PMID- 17332893 TI - Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. AB - HDL lowers the risk for atherosclerotic cardiovascular disease by promoting cholesterol efflux from macrophage foam cells. However, other antiatherosclerotic properties of HDL are poorly understood. To test the hypothesis that the lipoprotein carries proteins that might have novel cardioprotective activities, we used shotgun proteomics to investigate the composition of HDL isolated from healthy subjects and subjects with coronary artery disease (CAD). Unexpectedly, our analytical strategy identified multiple complement-regulatory proteins and a diverse array of distinct serpins with serine-type endopeptidase inhibitor activity. Many acute-phase response proteins were also detected, supporting the proposal that HDL is of central importance in inflammation. Mass spectrometry and biochemical analyses demonstrated that HDL3 from subjects with CAD was selectively enriched in apoE, raising the possibility that HDL carries a unique cargo of proteins in humans with clinically significant cardiovascular disease. Collectively, our observations suggest that HDL plays previously unsuspected roles in regulating the complement system and protecting tissue from proteolysis and that the protein cargo of HDL contributes to its antiinflammatory and antiatherogenic properties. PMID- 17332894 TI - Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II. AB - Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression in lungs of ozone-resistant mice suggested an additional role protecting against inhaled oxidants. After ozone exposure, MARCO-/- mice showed greater lung injury than did MARCO+/+ mice. Ozone is known to generate oxidized, proinflammatory lipids in lung lining fluid, such as 5beta,6beta-epoxycholesterol (beta-epoxide) and 1 palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC). Intratracheal instillation of either lipid caused substantial neutrophil influx in MARCO-/- mice, but had no effect in MARCO+/+ mice. Normal AMs showed greater uptake in vitro of beta-epoxide compared with MARCO-/- AMs, consistent with SRA function in binding oxidized lipids. SR-AI/II-/- mice showed similar enhanced acute lung inflammation after beta-epoxide or another inhaled oxidant (aerosolized leachate of residual oil fly ash). In contrast, subacute ozone exposure did not enhance inflammation in SR-AI/II-/- versus SR-AI/II+/+ mice, reflecting increased AM expression of MARCO. These data identify what we believe to be a novel function for AM SRAs in decreasing pulmonary inflammation after oxidant inhalation by scavenging proinflammatory oxidized lipids from lung lining fluids. PMID- 17332895 TI - Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. AB - Coenzyme Q10 (CoQ10) plays a pivotal role in oxidative phosphorylation (OXPHOS), as it distributes electrons among the various dehydrogenases and the cytochrome segments of the respiratory chain. We have identified 2 novel inborn errors of CoQ10 biosynthesis in 2 distinct families. In both cases, enzymologic studies showed that quinone-dependent OXPHOS activities were in the range of the lowest control values, while OXPHOS enzyme activities were normal. CoQ10 deficiency was confirmed by restoration of normal OXPHOS activities after addition of quinone. A genome-wide search for homozygosity in family 1 identified a region of chromosome 10 encompassing the gene prenyldiphosphate synthase, subunit 1 (PDSS1), which encodes the human ortholog of the yeast COQ1 gene, a key enzyme of CoQ10 synthesis. Sequencing of PDSS1 identified a homozygous nucleotide substitution modifying a conserved amino acid of the protein (D308E). In the second family, direct sequencing of OH-benzoate polyprenyltransferase (COQ2), the human ortholog of the yeast COQ2 gene, identified a single base pair frameshift deletion resulting in a premature stop codon (c.1198delT, N401fsX415). Transformation of yeast Deltacoq1 and Deltacoq2 strains by mutant yeast COQ1 and mutant human COQ2 genes, respectively, resulted in defective growth on respiratory medium, indicating that these mutations are indeed the cause of OXPHOS deficiency. PMID- 17332897 TI - The story so far in R&D. AB - Human diseases are a significant cause of suffering and mortality and lead to a consequential need for effective therapies. The need for therapy is as old as human history itself. Therapy has progressed from an age of administration of herbal remedies and organ extracts to an era of serendipitous drug discovery, when the pharmaceutical industry was born, to the dominance of medicinal chemistry and more recently, to the revolutionary advances--genetic engineering and monoclonal antibody technology, high-speed technologies, gene therapy and the deciphering of the human genome--which promise the discovery of completely new targets for new medicines as well as the great potential of personalized therapy. PMID- 17332898 TI - The year's new drugs and biologics--2006. AB - This annual series presents new drugs and biologics that were launched or approved for the first time during the previous year. In 2006, 41 new medicines- this figure includes both drugs and biologics for therapeutic use as well as new diagnostic agents and, for the first time this year, an important new herbal medicine--reached their first markets. Drug repositioning continues to have a significant impact, with line extensions (new indications, new formulations and new combinations of previously marketed products) accounting for more than 20 of the new medicines launched in 2006. This year's edition of the article also includes several new features: a deeper insight into the five first-in-class drugs launched for the first time last year, providing a better understanding of their novel mechanisms of action; an analysis of the discovery and development periods for the year's new products; a comprehensive overview of drug repositioning as a strategy for extending the life spans of medicines; and an analysis of the market for these new medicines. New generic drug approvals are also reviewed, as well as a brief glimpse at selected drugs and biologics which could reach their first markets in the foreseeable future. PMID- 17332896 TI - Aldosterone-induced Sgk1 relieves Dot1a-Af9-mediated transcriptional repression of epithelial Na+ channel alpha. AB - Aldosterone plays a major role in the regulation of salt balance and the pathophysiology of cardiovascular and renal diseases. Many aldosterone-regulated genes--including that encoding the epithelial Na+ channel (ENaC), a key arbiter of Na+ transport in the kidney and other epithelia--have been identified, but the mechanisms by which the hormone modifies chromatin structure and thus transcription remain unknown. We previously described the basal repression of ENaCalpha by a complex containing the histone H3 Lys79 methyltransferase disruptor of telomeric silencing alternative splice variant a (Dot1a) and the putative transcription factor ALL1-fused gene from chromosome 9 (Af9) as well as the release of this repression by aldosterone treatment. Here we provide evidence from renal collecting duct cells and serum- and glucocorticoid-induced kinase-1 (Sgk1) WT and knockout mice that Sgk1 phosphorylated Af9, thereby impairing the Dot1a-Af9 interaction and leading to targeted histone H3 Lys79 hypomethylation at the ENaCalpha promoter and derepression of ENaCalpha transcription. Thus, Af9 is a physiologic target of Sgk1, and Sgk1 negatively regulates the Dot1a-Af9 repressor complex that controls transcription of ENaCalpha and likely other aldosterone-induced genes. PMID- 17332899 TI - Promoting, improving and accelerating the drug development and approval processes. AB - Three programs originating at drug regulatory agencies have been set up with the objective of facilitating, potentiating and accelerating the development of new medicines. The U.S. FDA and EMEA have introduced a new phase of clinical testing designed to ease the transition from lab to clinic, known as microdosing in Europe and as phase 0 in the United States. Orphan drug programs have been established in the U.S., E.U., Japan and Australia to encourage the development of medicines to treat rare diseases. The FDA's fast track development program was set up to facilitate the development and expedite the review of drugs that treat a broad range of serious diseases and fill an unmet medical need. This article reviews the three programs and provides a capsule view of new developments in these vital areas during the year 2006. PMID- 17332900 TI - Overcoming the challenges in the pharma/biotech industry. AB - In the face of patent expirations at a time of declining innovation across the industry, companies are restructuring their research and development operations and are pursuing an aggressive strategy of acquisitions, licensing deals and research collaborations to boost their drug pipelines. PMID- 17332901 TI - Listeria--review of epidemiology and pathogenesis. AB - Listeria monocytogenes (commonly called Listeria) is a Gram-positive facultatively intracellular foodborne pathogen often found in food and elsewhere in nature. It can cause a rare but serious disease called listeriosis, especially among pregnant women, the elderly or individuals with a weakened immune system. In serious cases, it can lead to brain infection and even death. Listeria is more likely to cause death than other bacteria that cause food poisoning. In fact, 20 to 30% of food borne listeriosis infections in high-risk individuals may be fatal. Recent technological developments have increased the ability of scientists to identify the cause of foodborne illnesses. L. monocytogenes has been used as a model organism for the study of intracellular parasitism. Whilst the basic mechanisms of cellular pathogenesis have been elucidated by a series of elegant studies, recent research has begun to focus upon the gastrointestinal phase of L. monocytogenes infection. Epidemiological studies of outbreaks of human disease now demonstrate that the pathogen can cause gastroenteritis in the absence of invasive disease and associated mortality. Elucidation of whole genome sequences and virulence determinants have greatly contributed to understanding of the organism and its infection pathways. PMID- 17332902 TI - Isolation and characterization of marine luminous bacteria from shallow coastal waters of Taiwan. AB - BACKGROUND AND PURPOSE: Marine luminous bacteria were isolated and identified from samples in shallow coastal waters of Taiwan during the relatively warm seasons. METHODS: Identification of the luminous isolates was performed based on differences of phenotypic and genotypic characteristics together with data from phylogenetic analysis. RESULTS: Twenty seven strains of marine luminous bacteria were isolated. They were divided into five types based on differences of phenotypic characteristics. However, they could be clustered into only two genotypes according to the analysis of restriction patterns of polymerase chain reaction-amplified 16S rRNA genes digested with various restriction enzymes. The characterization data together with the 16S rRNA gene-based phylogenetic analysis revealed that the isolates included in phenotype I (seven isolates) could be Photobacterium leiognathi, and those included in phenotypes II-V (twenty isolates) might be classified as Vibrio harveyi. However, phylogeny based on gyrB sequences indicated that phenotypes II-V could be classified into two species, V. harveyi and Vibrio campbellii. CONCLUSION: Culturable luminous bacteria in the shallow coastal waters of Taiwan during the sampling period are dominated by V. harveyi/campbellii and P. leiognathi, and the former species appeared to be more prevalent and numerous than the latter species in general. PMID- 17332903 TI - Studies on synonymous codon and amino acid usages in Aeromonas hydrophila phage Aeh1: architecture of protein-coding genes and therapeutic implications. AB - BACKGROUND AND PURPOSE: Codon and amino acid usage biases determined in numerous organisms have deciphered the architectures of their protein-coding genes to some extent. To understand the architecture of protein-coding genes of Aeromonas phages, codon and amino acid usage biases have been investigated in the protein coding genes of the Aeromonas hydrophila phage Aeh1. METHODS: In order to study synonymous codon and amino acid usage biases in Aeh1, all of its protein-coding genes were downloaded and analyzed by standard software programs. RESULTS: Phage Aeh1 harbors an AT-rich genome. The third position of its synonymous codons carries mostly A or T base and mutational pressure strongly influences the synonymous codon usage bias. Translational selection also influences the codon usage of Aeh1 as its putatively lowly- and highly-expressed genes are influenced by Aeh1-specific tRNAs and by the abundant cellular tRNAs, respectively. Further analysis of amino acid usage shows that amino acid residues are also not randomly utilized in Aeh1 proteins and factors such as hydropathy, aromaticity and cysteine content are mostly responsible for the variation of amino acid usage in Aeh1 proteins. CONCLUSIONS: As Aeh1 does not carry any toxin/antibiotic resistant gene but carries moderately highly expressed genes and relatively few AhdI sites, this study proposes that Aeh1 may be utilized as a therapeutic agent for A. hydrophila infections. While codon usage bias in Aeh1 is dictated both by mutational pressure and translational selection, amino acid usage bias in Aeh1 is influenced by hydropathy, aromaticity and cysteine content. Phage Aeh1 may be utilized in phage therapy. PMID- 17332904 TI - Outcome of herpes simplex encephalitis in children. AB - BACKGROUND AND PURPOSE: Herpes simplex encephalitis (HSE) can cause high mortality and morbidity in children. Since local data of HSE in children are rare, we performed a retrospective study to evaluate the prognostic factors and outcome of HSE in Taiwan. METHODS: Children were enrolled into this study if they were diagnosed as having encephalitis and also had positive polymerase chain reaction for herpes simplex virus (HSV) from cerebrospinal fluid, and/or positive immunoglobulin M or at least four-fold elevation of immunoglobulin G against HSV type 1 or type 2 from serum during the period from December 1, 1984 to January 31, 2003. RESULTS: Forty patients were enrolled in this study. Twenty six patients (65%) had good outcome and 14 (35%) had poor outcome. No mortality or recurrence was found. Three-fifths of the patients were between 1 year and 6 years of age. Fever (75%) was the most common finding at admission, followed by seizures (63%), lethargy (60%), and altered consciousness (48%). Seizure and lethargy at the time of admission were more common in the poor outcome group (71% vs 58% and 64% vs 58%). Abnormal computed tomography/magnetic resonance imaging findings were found in 63% of patients in whom the examinations were performed. Abnormal electroencephalogram (EEG) findings were noted in 79% of tested patients. Acyclovir was used to treat 29 patients (73%). Abnormal neuroimaging or EEG findings were more prevalent in patients with poor outcome (75% vs 55% and 92% vs 71%), as well as delayed (>/=3 days) initiation of acyclovir therapy (92% vs 71%). There was no significant difference between the poor and good outcome groups in gender, age distribution, and clinical presentation. CONCLUSION: As we cannot predict the outcome of patients with HSE in the early beginning of illness and delay of treatment may cause disaster, early diagnosis and prompt acyclovir initiation are important requirements for successful management. PMID- 17332905 TI - Microbiology of diabetic foot infections in a teaching hospital in Malaysia: a retrospective study of 194 cases. AB - BACKGROUND AND PURPOSE: Diabetes mellitus is a progressive disease with chronic complications. Foot infections are a major complication of diabetes and eventually lead to development of gangrene and lower extremity amputation. The microbiological characteristics of diabetic foot infections have not been extensively studied in Malaysia. This study investigated the microbiology of diabetic foot infections and their resistance to antibiotics in patients with diabetic foot infections treated at University of Malaya Medical Centre in Kuala Lumpur, Malaysia. METHODS: A retrospective analysis was conducted of clinical specimens taken from patients with diabetic foot infections over a 12-month period from July 1, 2004 to June 30, 2005. A total of 194 patients with positive clinical specimens were identified. The clinical specimens were cultured using standard aerobic and anaerobic microbiological techniques. Antibiotic sensitivity testing to different antimicrobial agents was carried out using the disk diffusion method. RESULTS: 287 pathogens were isolated from 194 patients, an average of 1.47 organisms per lesion. The most frequently isolated pathogens were Gram-negative bacteria (52%), including Proteus spp. (28%), Pseudomonas aeruginosa (25%), Klebsiella pneumoniae (15%) and Escherichia coli (9%). Gram positive bacteria accounted for 45% of all bacterial isolates. Staphylococcus aureus was predominant (44%) among Gram-positive bacteria, followed by Group B streptococci (25%) and Enterococcus spp. (9%). Antimicrobial susceptibility results showed that Gram-negative bacterial isolates were sensitive to imipenem and amikacin while vancomycin showed good activity against Gram-positive bacteria. CONCLUSION: The antibiogram results of this study suggest that pathogens remain sensitive to a number of widely used agents. Imipenem was equally effective against Gram-negative bacilli and Gram-positive cocci. PMID- 17332906 TI - Antimicrobial susceptibility pattern of clinical isolates of Pseudomonas aeruginosa in a tertiary care hospital. AB - BACKGROUND AND PURPOSE: Pseudomonas aeruginosa is an important cause of morbidity and mortality in hospitalized, critically ill patients and patients with underlying medical conditions such as cystic fibrosis, neutropenia, and iatrogenic immunosuppression. The prevalence of multiresistant P. aeruginosa isolates has been increasing. The aim of this study was to determine the antimicrobial susceptibility patterns in P. aeruginosa strains isolated at a university teaching hospital in Kuala Lumpur, Malaysia. METHODS: The Laboratory Information System of the microbiology department was retrospectively reviewed to determine the susceptibility patterns of P. aeruginosa isolates to anti pseudomonal antibiotics, from January to June 2005. Disk diffusion methods were employed and results were interpreted according to National Committee for Clinical Laboratory Standards guidelines. RESULTS: 505 clinical isolates of P. aeruginosa were tested. Major sources of these isolates included respiratory tract, wound, urine and blood. The rates of antimicrobial resistance of isolates were 6.73% to amikacin, 12.9% to gentamicin, 10.1% to netilmicin, 10.9% to ceftazidime, 11.3% to ciprofloxacin, 9.9% to imipenem, 10.8% to piperacillin, 9.4% to piperacillin-tazobactam and 0% to polymyxin B. Of the 505 isolates, 29 (5.74%) were found to be multidrug-resistant; these were most commonly isolated from respiratory tract specimens of patients in surgical units, followed by respiratory tract specimens in patients in medical units. CONCLUSIONS: The data in this study showed low rates of antibiotic resistance among P. aeruginosa isolates. Combinations of aminoglycosides plus beta-lactams or quinolones should be the appropriate choice for empirical therapy in P. aeruginosa infections. Active antibiotic susceptibility testing and surveillance should be continued in order to curtail the problem of antibiotic resistance. PMID- 17332907 TI - Elevated serum anti-endothelial cell autoantibodies titer is associated with lupus nephritis in patients with systemic lupus erythematosus. AB - BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease associated with endothelial dysfunction and the existence of multiple species of autoantibodies. However, the association between endothelial dysfunction and renal manifestations remains unclear in Taiwanese SLE patients. METHODS: Serum samples were collected from SLE patients with biopsy proven lupus nephritis (n = 32), stable SLE patients (n = 32) and healthy controls (n = 32). The SLE Disease Activity Index (SLEDAI) of SLE patients was scored, and levels of anti-endothelial cell antibodies (AECA) and anti endothelial activities in serum samples were measured by cell-enzyme-linked immunosorbent assay and crystal violet assay, respectively, using cultured human endothelial EA.hy926 cells. RESULTS: Significantly higher AECA (p<0.001) and anti endothelial activities (p<0.001) were found in sera from patients with lupus nephritis compared with that from stable SLE patients or controls. Moreover, AECA titers (p<0.001) and anti-endothelial activities (p<0.001) were strongly correlated with SLEDAI scores in these patients. CONCLUSION: The strong correlations of AECA and anti-endothelial activity with lupus nephritis activity support an endothelial origin for renal complications in Taiwanese SLE patients. PMID- 17332908 TI - In vitro synergy of baicalein and gentamicin against vancomycin-resistant Enterococcus. AB - BACKGROUND AND PURPOSE: Little is known about the possible synergism of baicalein, a bioactive flavone of Scutellariae radix (a Chinese herb), when used in conjunction with other antimicrobial agents against vancomycin-resistant Enterococcus (VRE). This in vitro study examined the possible synergism of the combination of baicalein and gentamicin against VRE. METHODS: Minimal inhibitory concentrations (MICs) of baicalein as well as gentamicin were determined against 39 clinical isolates of VRE by the agar dilution method. Synergistic activities were determined using the checkerboard method based on the fractional inhibitory concentration indices and also the time-kill method. Further time-kill studies were conducted with these two agents against one randomly chosen clinical isolate, VRE-096. RESULTS: Minimal concentrations inhibiting 50% (MIC(50)) and 90% (MIC(90)) of isolates for baicalein and gentamicin were all >256 microg/mL. Synergism between baicalein and gentamicin was demonstrated against four clinical isolates of VRE (VRE-70, VRE-940, VRE-096 and VRE-721). When approximately 5 x 10(5) colony-forming units/mL of VRE-096 was incubated with both baicalein at a concentration of 32 microg/mL (1/8 x MIC) and gentamicin at a concentration of 128 microg/mL (1/2 x MIC), there was an inhibitory effect against VRE that persisted for 48 h. At 48 h, the combination of baicalein and gentamicin at these respective concentrations resulted in a reduction of growth by approximately 2 orders of magnitude compared to that for the starting inoculum and by 3 orders of magnitude compared to that for baicalein alone, the more active single agent. CONCLUSION: This study demonstrated that baicalein and gentamicin can act synergistically in inhibiting VRE in vitro. PMID- 17332909 TI - An observational study on the empiric use of cefpirome in febrile neutropenia. AB - BACKGROUND AND PURPOSE: The objective of this study was to document the clinical experience of cefpirome use in the treatment of febrile neutropenia in everyday medical practice. METHODS: This was an open, non-controlled multicenter study. Patients with fever and neutropenia were started on cefpirome empirically. Response to therapy was evaluated 72 to 96 h after the beginning of treatment. The primary endpoint, clinical response, was classified as: improvement (disappearance of fever and the other signs and symptoms of infection) or failure (the patient died during the therapy or had no response to the antibiotic regimen; i.e., fever persisted and the patient's clinical condition was not improving, requiring a change in antibiotic therapy). The secondary endpoints were time to the resolution of fever and improvement of neutropenia, and microbiological response evaluated on-treatment or post-treatment. RESULTS: 140 patients were enrolled in this study; clinical response was analyzed on the clinically evaluated population after 72 to 96 h of treatment. Among the 69 evaluated patients, 58 patients (84.1%) were improved and 11 patients (15.9%) failed. Overall, among the enrolled 140 patients, 124 patients' clinical outcomes were improved after treatment and 16 patients failed. The mean time to fever resolution was 3.1 days. Mean temperature reduced from a baseline reading of 38.7 degrees C to 37.2 degrees C (p<0.0001). Moreover, the mean neutrophil count (342.7/mm(3) at baseline) increased significantly to 3664/mm(3) (p<0.0001) after 72 to 96 h of treatment. Twenty five pathogens were isolated from 20 patients (13 Gram-positive and 9 Gram-negative). The eradication rate was 72% on-treatment or post-treatment, and the mean time to eradication was 5 days. CONCLUSIONS: Cefpirome improves clinical signs and symptoms of infection and offers improved coverage against some Gram-positive and Gram-negative pathogens in patients with febrile neutropenia. Thus, cefpirome is likely to be a valuable and cost effective extended-spectrum agent for the empiric treatment of severe infections. PMID- 17332910 TI - Ten-year experience of juvenile dermatomyositis: a retrospective study. AB - BACKGROUND AND PURPOSE: Juvenile dermatomyositis (JDMS) is a rare multisystemic disease of unknown etiology that primarily affects muscle and skin. This study aimed to evaluate the initial laboratory data, clinical manifestations, complications, and clinical outcomes of patients with JDMS in Taiwan. METHODS: We reviewed medical charts of patients younger than 18 years with a diagnosis of JDMS at the pediatric department of National Taiwan University Hospital between 1994 and 2004. RESULTS: A total of 21 patients were included. The female-to-male ratio was 4.25:1. The mean age at onset of symptoms was 6.4 +/- 3.7 years (range, 2 to 14.2 years). The mean age at diagnosis was 6.9 +/- 3.9 years (range, 2.2 to 15 years). Among the initial cutaneous features, Gottron's rash (62%) and facial rash (including malar rash, 62%) were the most common findings. Gottron's rash was also the most common sign (81%) at any time during the disease course. Among other systemic features at disease onset, myalgia (33%) was the most common symptom, followed by arthralgia (19%) and dysphagia (19%). Interstitial pneumonitis was a complication in 2 patients, one of whom was a mortality case. Gastrointestinal tract vasculitis was highly suspected in one patient complicated with duodenal perforation and retroperitoneal abscess. Calcinosis developed in 6 patients (28.5%), and one of these patients presented with disseminated calcinosis. Five of 21 patients achieved drug-free remission for 28 to 94 months from the time they discontinued therapy to the end of the study. Two patients with diagnosis of amyopathic dermatomyositis were also included in this study. CONCLUSIONS: The long-term outcomes in this study are thought to be good. Because the understanding of the pathogenesis of JDMS is limited, certain complications are still troublesome clinically. PMID- 17332911 TI - Prevalence of atopy in children with type 1 diabetes mellitus in central Taiwan. AB - BACKGROUND AND PURPOSE: Atopic diseases, including asthma, eczema and allergic rhinitis, are characterized by a chronic inflammatory reaction mediated by T helper 2 (Th2) cells, while type 1 diabetes mellitus (T1D) is mediated by T helper 1 (Th1) cells. The 'balance' between Th1 and Th2 cells appears to be vitally important. Hence, it is a plausible hypothesis that the prevalence in Th2 mediated disease would be lower in patients with Th1-mediated disease. The aim of this study was to compare the prevalence of atopic diseases between children with T1D and age-matched controls, and investigate possible factors that influence the prevalence of atopic disease. METHODS: Parents of children with T1D in Taichung Veterans General Hospital were requested by pediatricians to complete the International Study of Asthma and Allergies in Childhood questionnaire on the prevalence of atopic diseases. Responses were compared with an age-matched control group. RESULTS: Questionnaires were evaluated from 100 T1D patients and 194 controls. After age-matching, the questionnaires of 54 T1D patients were included. Symptoms of asthma, allergic rhinitis and eczema were reported less often in the group of children with T1D compared with the control group (wheeze with exercise, p=0.044; nasal symptoms with itching eyes in the past 12 months, p=0.048; nasal allergy ever, p=0.038; skin rash in the past 12 months, p=0.044). In addition, the proportion of T1D patients with any asthmatic symptom (such as wheezing once in life, wheezing in the past 12 months, wheezing with exercise and dry cough at night in the past 12 months) was significantly lower than in controls (20.4% vs 36.6%, p=0.036). CONCLUSIONS: These results indicate that patients with T1D have a lower prevalence of atopic symptoms, especially asthma, which is consistent with the Th1/Th2 polarization concept. Environmental factors are another direct influence on the development of atopy in T1D patients. PMID- 17332912 TI - Tuberculous myositis: an unusual presentation of extrapulmonary tuberculosis. AB - The prevalence of Mycobacterium tuberculosis infection in Taiwan has increased in recent decades. Extrapulmonary infection accounts for 40% of all tuberculosis cases. Here we report a seven-year-old girl with culture-proven tuberculous myositis manifested as progressive enlargement of chest wall mass. No congenital or acquired immune deficiency could be traced at presentation. After surgical excision and completion of 6-month anti-tuberculous therapy, no recurrence of mass or any sequela was found during 6 months of follow-up. PMID- 17332913 TI - Successful treatment of life-threatening melioidosis with activated protein C and meropenem. AB - Melioidosis is an endemic disease in southeast Asia and northern Australia, caused by Burkholderia pseudomallei. A typhoon-related outbreak occurred in southern Taiwan in July 2005. High mortality in melioidosis associated with bacteremic pneumonia and septic shock. We report a patient with life-threatening melioidosis who developed rapid progression of bacteremic pneumonia with acute respiratory distress syndrome, septic shock and multiple organ dysfunction and was successfully treated with recombinant human activated protein C (rhAPC) and meropenem. Although rhAPC has been reported to reduce the mortality of severe septic shock caused by various pathogens, to our best knowledge, this is the first reported case of rhAPC application in life-threatening melioidosis. PMID- 17332914 TI - PLAG1, the prototype of the PLAG gene family: versatility in tumour development (review). AB - Recent studies of human tumours as well as genetically engineered mouse tumour models have established the importance and versatility of the PLAG1 oncogene in tumourigenesis. The PLAG1 proto-oncogene was discovered by studying the t(3;8)(p21;q12) chromosome translocation, which frequently occurs in human pleomorphic adenomas of the salivary glands. PLAG1 encodes a developmentally regulated, SUMOylated and phosphorylated zinc finger transcription factor, recognizes a specific bipartite DNA consensus sequence regulating expression of a spectrum of target genes, and has two structurally related family members, i.e. the PLAGL1 and PLAGL2 gene. Ectopic PLAG1 overexpression, in many cases due to promoter swapping, causes deregulation of expression of a variety of PLAG1 target genes. This was established by microarray analysis, which indicated that the oncogenic capability of PLAG1 is mediated, at least partly, by the IGF-II mitogenic signaling pathway. Oncogenic activation of PLAG1 is also a crucial event in other human tumours, including lipoblastoma, hepatoblastoma, and AML. The oncogenic potential of PLAG1 has been confirmed in in vitro experiments, which also established IGF-II and IGF-IR as key pathway elements, similarly as in many human tumours. Furthermore, generation of conditional PLAG1 transgenic mouse strains revealed tumour development in a variety of targeted tissues, establishing the versatility of the PLAG1 oncogene and pointing towards a window of opportunity for therapeutic intervention studies. In contrast to the pleiotropic oncogenic potential of PLAG1, its family member PLAGL1, which is localized in an imprinted region on chromosome 6q24-25, is defined by various studies as a tumour-suppressor gene. Finally, the PLAGL2 family member is not only structurally but also functionally more closely related to PLAG1 and has recently also been implicated in AML, both in humans and in genetically modified mice. Collectively, these observations emphasize a more general importance of the PLAG1 gene in tumour development. In light of the fact that IGF-IR is implicated in many human tumours, the diversity in PLAG1-induced mouse tumour models, most of which seem to involve Igf2 signaling, provides useful in vivo platforms to start testing the effects of inhibitors, such as Igf-1r inhibitors, on tumour development in distinct tissues or organ types. PMID- 17332915 TI - Overexpression of the opioid growth factor receptor potentiates growth inhibition in human pancreatic cancer cells. AB - The opioid growth factor (OGF), [Met5]-enkephalin, and OGF receptor (OGFr) form an inhibitory axis regulating the growth of human pancreatic cancer. This study examined whether overexpression of OGFr decreases the growth of pancreatic cells in vitro. MIA PaCa-2 cells were transfected with OGFr cDNA, and six clonal lines were examined for protein expression and function. OGFr binding assays revealed a 2.3- to 5.6-fold increase in binding capacity from wild-type (WT) and empty vector (EV) controls; binding affinity was comparable in all groups. OGFr protein expression, as measured by immunohistochemistry and Western blotting, was enhanced in clonal cell lines compared to controls. Doubling times of OGFr clonal lines were 47-91% longer than in the WT/EV groups for all but one clonal line. DNA synthesis of cells overexpressing OGFr was diminished from the WT/EV groups by 28-52%. Addition of exogenous OGF further reduced (14-31%) the cell growth of clonal lines, and the effects of exogenous OGF were receptor-mediated. Exposure of cells overexpressing OGFr to naltrexone increased the cell number by up to 9.4 fold. OGF was identified as the only opioid peptide to depress cell replication in the transfected cell lines. Neutralization of endogenous OGF with antibodies to this peptide elevated the cell number in clonal cell lines. These data identify OGFr at the molecular level as integral to regulating the cell replication of human pancreatic cancer, and support treatment modalities that amplify OGFr in order to decrease the growth of these neoplasias. PMID- 17332916 TI - Cyclooxygenase-2 uses the protein kinase C/ interleukin-8/urokinase-type plasminogen activator pathway to increase the invasiveness of breast cancer cells. AB - Cyclooxygenase-2 (COX-2) increases breast cancer cell invasion. Expression of various pro-angiogenic and pro-invasive factors has been correlated with high expression of COX-2. However, whether these factors are essential to COX-2 mediated breast cancer invasion, and the mechanisms by which COX-2 increases the expression of these factors are unknown. Our microarray results indicate that higher COX-2 expression was associated with increased levels of interleukin-8 (IL 8), a key factor in breast cancer invasion and metastasis. COX-2 overexpressing cells (MCF-7/COX-2), generated by transfecting COX-2-encoding plasmids into the poorly invasive MCF-7 breast cancer cells, were more invasive and produced higher IL-8 levels than the parental cells. To investigate the role of IL-8 in COX-2 mediated invasion, MCF-7 parental cells were incubated with IL-8. Exogenous IL-8 increased the invasiveness of MCF-7 cells. IL-8 is one pathway by which COX-2 mediates breast cancer invasion. Protein kinase A (PKA) and protein kinase C (PKC) are activated by COX-2 and are involved in IL-8 regulation. Inhibition of PKC, not PKA, decreased IL-8 production and invasion in MCF-7/COX-2 cells. Activation of PKC, not PKA, increased IL-8 production and invasion in MCF-7 cells. Thus, the invasive effects of COX-2 are mediated by PKC, not PKA. Activity of the urokinase-type plasminogen activator (uPA) was increased in MCF-7 cells by COX-2 overexpression or by the addition of a PKC activator or by IL-8. Inhibition of PKC decreased uPA activity in MCF-7/COX-2 cells. Furthermore, inhibition of uPA activity decreased the invasiveness of MCF-7/COX-2 cells, indicating that uPA was essential to COX-2-mediated invasion. Herein we demonstrate for the first time a detailed mechanism by which COX-2 increases breast cancer invasion: the PKC/IL-8/uPA pathway. PMID- 17332917 TI - Silencing hypoxia-inducible factor-1alpha inhibits cell migration and invasion under hypoxic environment in malignant gliomas. AB - Malignant gliomas are characterized by active invasiveness, necrosis, and vascular proliferation. These pathological features have been speculated to be caused by tissue hypoxia. Hypoxia-inducible factor-1 (HIF-1), which is controlled by rapid stabilization of the HIF-1alpha subunit, is a pivotal transcriptional factor in the cellular response to hypoxia. Although many studies have described the relationship between tumor angiogenesis and hypoxic environment, the roles of HIF-1 in cell invasion have been barely elucidated in malignant gliomas. We investigated the role of HIF-1alpha in the motile and invasive activities of human glioma cells under hypoxia. Four malignant glioma cell lines, U87MG, U251MG, U373MG, and LN18, were cultured under 21 and 1% oxygen concentration. Expression of HIF-1alpha under hypoxia was observed to be much higher than that under normoxia in all cell lines. Introducing HIF-1alpha-targeted small interfering RNA (HIF-1alpha siRNA) into the glioma cell lines resulted in downregulation of HIF-1alpha expression, and significantly suppressed glioma cell migration in vitro. Furthermore, invasiveness was significantly reduced in the cells transfected with HIF-1alpha siRNA compared with those transfected with the control siRNA. Co-culture of glioma spheroids and rat brain slices showed that HIF-1alpha siRNA-transfected glioma cells failed to invade the surrounding normal brain tissue in an organotypic brain slice model. These effects of HIF-1alpha siRNA were more conspicuous under hypoxia than under normoxia. In addition, under hypoxic conditions, the level of matrix metalloproteinase (MMP)-2 mRNA was upregulated, and that of tissue inhibitor of metalloproteinase (TIMP)-2 was downregulated in all glioma cell lines. Treatment with HIF-1alpha siRNA resulted in downregulation of MMP-2 mRNA and upregulation of TIMP-2 mRNA. Furthermore, the enzyme activities of MMP-2 and MMP-9, both of which were activated by hypoxia, decreased with the introduction of HIF-1alpha siRNA. These findings suggest that overexpression of HIF-1alpha induced by hypoxic stress is an essential event in the activation of glioma cell motility through alteration of invasion-related molecules. Targeting the HIF-1alpha molecule may be a novel therapeutic strategy for malignant gliomas. PMID- 17332918 TI - TNF expressed by tumor-associated macrophages, but not microglia, can eliminate glioma. AB - It is well known that tumor necrosis factor (TNF) can have both contrary and pleiotropic effects in anti-tumor immune response. In the present study, we prepared two different tumor cell-based immunotherapy models: MCA38 adenocarcinoma and GL261 glioma intracranial interleukin-2 (IL-2)-based. Each tumor was transfected to express IL-2 with or without expression of the soluble form of tumor necrosis factor receptor type II (sTNFRII). Although mice in which TNF is blocked survive longer than IL-2 alone (35.2 versus 26 days), the reverse was observed for GL261 glioma. The differential effect on tumor growth implies enhanced TNF sensitivity of GL261 compared to MCA38. This notion is supported by the observation that TNF induces apoptosis in GL261 but not MCA38 tumors. We further examined tumor infiltrating CD11b+F4/80+ macrophages (or tumor-associated macrophages: TAM) for TNF production in vivo and found that TAM express cell surface TNF implying a role in eliminating glioma cells mediated by the cell surface form of TNF. PMID- 17332919 TI - Human papillomavirus: its identity and controversial role in oral oncogenesis, premalignant and malignant lesions (review). AB - Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the ano-genital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36) -risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-beta2. Since these viral oncoproteins are capable of transforming primary human keratinocytes from either genital or upper respiratory tract epithelia, they have been considered to play a role in disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and, possibly, also to oral squamous cell carcinoma (OSCC). Recently, the oncogene HPV-E5 has also been found to transform cells by modulating growth factor receptors. On the basis of the high, although very variable, frequency of HR-HPV in OSCC, an oral malignant potential of HPV infection has been hypothesised but not definitively confirmed. Major aims of this review are to update the understanding of HPV activities with respect to oral oncology and to comment on the HPV DNA reported frequencies in OSCC and potentially malignant oral lesions. A computer database search was performed, through the use of MEDLINE (PubMED) and Cochrane Library, for the last three decades. Search key words used were: human papillomavirus, HPV and cancer, HPV and oral lesions, HPV and oral premalignant lesions, HPV and oral cancer, HPV and HNSCC, HPV and oral mucosa. The search was of all fields, all languages and all dates available. PMID- 17332920 TI - Expression of interleukin-11 (IL-11) and IL-11 receptor alpha in human gastric carcinoma and IL-11 upregulates the invasive activity of human gastric carcinoma cells. AB - Previous investigations have shown that interleukin-11 (IL-11) and the IL-11 receptor (IL-11R) have been correlated with the regulation of tumor progression, cellular growth and differentiation in several malignant tumors. The objectives of this study were to clarify the role of IL-11 and IL-11Ralpha in human gastric carcinoma. IL-11 and IL-11Ralpha were studied in 73 cases of surgically resected human gastric adenocarcinomas by immunohistochemistry. The invasive activity and cell signaling pathway of gastric carcinoma cell lines were also examined. Among the 73 cases of adenocarcinoma, 53 (72.6%) and 47 cases (64.4%) showed positive staining in carcinoma cells for the IL-11 and IL-11Ralpha proteins, respectively. Histologically, IL-11 expression correlated only with Lauren's classification (p<0.05). The expression of IL-11Ralpha correlated with the grade of tumor invasion (p<0.05) and vessel infiltration (p<0.01). All of the four gastric carcinoma cell lines expressed both IL-11 and IL-11Ralpha proteins in western blot analysis. Recombinant human IL-11 (rhIL-11) promoted the migration of SCH cells by the activation of the phosphatidylinositol-3 kinase pathway. Wortmannin diminished the promotion of chemotactic motility and invasive activity by rhIL 11. These findings suggest that the IL-11/IL-11R pathway plays an important role in the progression and the differentiation of human gastric carcinomas. PMID- 17332921 TI - Identification of DR9-restricted XAGE antigen on lung adenocarcinoma recognized by autologous CD4 T-cells. AB - We previously demonstrated a dominant IgG response against XAGE-1b antigen in a lung cancer patient by serological analysis of antigens by recombinant expression cloning (SEREX) analysis using a cDNA library from the autologous OU-LU-6 tumor cell line. In this study, we investigated recognition of XAGE-1b on OU-LU-6 tumor by the patient CD4-expressing tumor-infiltrating lymphocytes (CD4 TIL). The response of CD4 TIL obtained from malignant pleural effusion was determined against autologous OU-LU-6 tumor cells and XAGE-1b mRNA-transfected PHA stimulated CD4 T-cells (T-APC) from healthy individuals sharing HLA-DR with the patient by performing IFNgamma secretion and ELISPOT assays. The patient CD4 TIL recognized OU-LU-6 in an HLA-DR-restricted manner and XAGE-1b mRNA-transfected T APC derived from DRB1 *0901-sharing healthy donor (HD)1 and HD2, but not DRB1 *1101-sharing HD3 or HD4. Epitope analysis using 17 18-mer peptides with 12 overlapping amino acids revealed that the CD4 TIL recognized XAGE-1b 33-49. The findings suggest that the patient CD4 T-cells recognized the XAGE-1b 33-49 related epitope on autologous OU-LU-6 tumor cells in a manner restricted by DR *0901. PMID- 17332922 TI - Mild hyperthermia predisposes tumor cells to undergo apoptosis upon treatment with onconase. AB - Onconase (ONC), (ranpirnase) a cytotoxic ribonuclease isolated from amphibian oocytes and early embryos targeting tumor cells in vitro and in vivo, is currently in a confirmatory Phase IIIb clinical trial for unresectable malignant mesothelioma where it demonstrates antitumor activity with relatively minor overall toxicity to patients. Since hyperthermia has been shown to be synergistic with certain antitumor modalities, the aim of the present study was to explore whether the cytotoxic effects of ONC can be enhanced under conditions of mild hyperthermia. Treatment of human lymphoblastoid TK6 cells with 2 or 5 microg/ml of ONC at 40 degrees C for 24 or 48 h led to 64-200% enhancement in incidence of apoptosis assessed by frequency of cells showing the presence of activated (cleaved) caspase-3 or activated serine proteases, compared to treatment at 37.5 degrees C. The incidence of apoptosis at 40 degrees C in the absence of ONC was unchanged compared to 37.5 degrees C, for up to 48 h. Although at 41 degrees C in absence of ONC the incidence of apoptosis was elevated compared to 37 degrees C the cytotoxicity of ONC was further enhanced and the overall pro-apoptotic effect was above the level of additive effects of ONC plus that of 41 degrees C hyperthermia. While the mechanism of the observed enhancement of ONC cytotoxicity is currently under investigation, the findings suggest that a combination of ONC and mild hyperthermia should be explored to increase effectiveness of ONC in cancer treatment. PMID- 17332923 TI - Expression of glycolytic enzymes is increased in pancreatic cancerous tissues as evidenced by proteomic profiling by two-dimensional electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry. AB - The prognosis of patients with pancreatic cancer is very poor because of late diagnosis and the lack of response to various therapies. We tried to identify proteins that might be available for early diagnosis and effective therapies by proteomic profiling of pancreatic cancer tissues. Pancreatic cancerous and paired non-cancerous tissues obtained from surgical resections or autopsies of 10 patients were analyzed by two-dimensional gel electrophoresis. The differential display showed 11 spots whose expression was increased in cancerous tissues compared with the paired non-cancerous tissues. The liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) system identified the spots as alpha enolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), triosephosphate isomerase, transgelin, calmodulin, superoxide dismutase(Mn) mitochondrial precursor, glutathione S-transferase P, cyclophilin A, protein disulfide isomerase A3 precursor, and apolipoprotein A-I precursor. Two of the 11 spots were detected as GAPDH. We noticed that 4 of 11 spots were enzymes involved in glycolytic pathway. Increased glycolysis in cancer cells has been regarded as the effect of intratumoral hypoxia and is possibly associated with tumor invasion, metastasis or resistance to therapies. These glycolytic proteins and transgelin, were confirmed by Western blotting and immunohistochemistry. PMID- 17332924 TI - An automated nanoliter dispenser for staining individual biopsies in tissue microarrays. AB - In the field of molecular analysis of cancer, there exists a need for a clinical device that can automate protocols for immunohistochemical and in situ hybridization diagnostic staining on tissue microarrays. The tissue microarray antibody spotter (TMAS) has been developed to provide fundamental improvements over current histological staining techniques by enabling precision application of reagents to individual biopsies within a tissue microarray. This allows for multiplexed reactions on a single slide and promises to significantly reduce costs associated with immunohistochemistry and in situ hybridization based assays. Additionally, because TMAS allows for testing of different biomarkers on each element of a tissue array, a complete cancer profile can be obtained from a single TMA slide. Ultimately this may lead to cost-effective, faster and more accurate diagnosis of the patient. PMID- 17332925 TI - Ephrin-A1 is a negative regulator in glioma through down-regulation of EphA2 and FAK. AB - Eph receptors, the largest receptor tyrosine kinases, and their ephrin ligands play important roles in axon guidance and cell migration during development of the nervous system. Recently, these molecules are also found involved in tumorigenesis of different kinds of cancers. In this study, we demonstrated that expression of ephrin-A1 was dramatically down-regulated in glioma cell lines and in primary gliomas compared to the matched normal tissues. Forced expression of ephrin-A1 attenuated cell migration, cell proliferation, and adhesion-independent growth in human glioma U251 cells. EphA2, a receptor for ephrin-A1 and an oncoprotein, was greatly decreased in ephrin-A1-transfected glioma cells. Overexpression of ephrin-A1 stimulated activation of EphA2 by phosphorylation and led to its degradation. Furthermore, focal adhesion kinase (FAK), a known downstream molecule of EphA2, was also down-regulated in the ephrin-A1 transfected cells. These results suggested that ephrin-A1 serves as a critical negative regulator in the tumorigenesis of gliomas by down-regulating EphA2 and FAK, which may provide potential valuable targets for therapeutic intervention. PMID- 17332926 TI - The influence of tumor oxygenation on hypoxia imaging in murine squamous cell carcinoma using [64Cu]Cu-ATSM or [18F]Fluoromisonidazole positron emission tomography. AB - [64Cu]Cu(II)-ATSM (64Cu-ATSM) and [18F]-Fluoromisonidazole (18F-FMiso) tumor binding as assessed by positron emisson topography (PET) was used to determine the responsiveness of each probe to modulation in tumor oxygenation levels in the SCCVII tumor model. Animals bearing the SCCVII tumor were injected with 64Cu-ATSM or 18F-FMiso followed by dynamic small animal PET imaging. Animals were imaged with both agents using different inspired oxygen mixtures (air, 10% oxygen, carbogen) which modulated tumor hypoxia as independently assessed by the hypoxia marker pimonidazole. The extent of hypoxia in the SCCVII tumor as monitored by the pimonidazole hypoxia marker was found to be in the following order: 10% oxygen>air>carbogen. Tumor uptake of 64Cu-ATSM could not be changed if the tumor was oxygenated using carbogen inhalation 90 min post-injection suggesting irreversible cellular uptake of the 64Cu-ATSM complex. A small but significant paradoxical increase in 64Cu-ATSM tumor uptake was observed for animals breathing air or carbogen compared to 10% oxygen. There was a positive trend toward 18F FMiso tumor uptake as a function of changing hypoxia levels in agreement with the pimonidazole data. 64Cu-ATSM tumor uptake was unable to predictably detect changes in varying amounts of hypoxia when oxygenation levels in SCCVII tumors were modulated. 18F-FMiso tumor uptake was more responsive to changing levels of hypoxia. While the mechanism of nitroimidazole binding to hypoxic cells has been extensively studied, the avid binding of Cu-ATSM to tumors may involve other mechanisms independent of hypoxia that warrant further study. PMID- 17332927 TI - Insulin-like growth factor binding protein-4 gene therapy increases apoptosis by altering Bcl-2 and Bax proteins and decreases angiogenesis in colorectal cancer. AB - Insulin-like growth factors are known to inhibit apoptosis and promote tumour angiogenesis. Previously we have shown that insulin-like growth factor binding protein-4 (IGFBP-4) gene therapy increased apoptosis and decreased mitosis in colon cancer. In this experiment we used HT-29 colon cancer cells to induce subcutaneous cancers in nude mice and administered either the mammalian expression vector with IGFBP-4 insert or vector only around the tumour site. Three weeks after gene transfer, tumours were harvested and expressions of Bax, Bcl-2 and IGF-I receptor in tumours were determined by Western blotting and immunofluorescence. Micro-vessel counting was performed by immunostaining with CD34 and von Willebrand antibodies. Results showed that tumours treated with IGFBP-4 gene had higher expression of Bax, lower expression of Bcl-2 and IGF-I receptor. Bcl-2 was localised to tumour cell cytoplasm while Bax was expressed both in the interstitial area and cytoplasm. IGFBP-4 treatment also decreased micro-vessel count in tumour tissues. Micro-vessels were mainly located in the periphery and interstitial area. This experiment shows that IGFBP-4 gene therapy increases tumour apoptosis via altering the expressions of Bcl-2 and Bax and decreasing the angiogenesis in colorectal cancer. PMID- 17332928 TI - Novel natural immunogenic peptides from Numb1 and Notch1 proteins for CD8+ cells in ovarian ascites. AB - Notch is a plasma membrane receptor involved in the control of cell fate specification and in the maintenance of the balance between proliferation and differentiation in many cell lineages. Disruption of Notch has been implicated in a variety of hematological and solid cancers. Numb is also expressed in many adult mammalian cells. Adult cells divide symmetrically, and Numb is symmetrically partitioned at mitosis. The Numb-mediated regulation of Notch is believed to play a causative role in naturally occurring breast cancers. Reduction of Numb levels in breast tumors is regulated by proteasomal degradation. We reasoned that if the disregulated negative control of Notch by Numb protein is the consequence of Numb proteasomal degradation, then degradation of Numb can generate peptides which are transported, presented by MHC-I molecules. Surprisingly we found few candidate naturally processed peptides from Notch1, Notch2, and Numb1. CD8+ T cells expressing TCRs which specifically recognized peptides Notch1 (2112-2120) and Numb1 (87-95) were presented in the ascites of ovarian cancer patients. Many of these cells were differentiated and expressed high levels of Perforin. The natural immunogenicity of Notch1 and particularly of Numb1 suggests a mechanism of immunosurveillance which is overcome during tumor progression. Immunotherapy with tumor antigens from Notch and Numb should be important for treatment of cancer patients. PMID- 17332929 TI - Preferential association of prostate cancer cells expressing prostate specific membrane antigen to bone marrow matrix. AB - Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed almost exclusively in prostatic epithelial cells. Expression of PSMA is elevated in prostate cancer, with levels closely correlated with disease grade. Although the highest levels of PSMA expression are associated with high-grade, hormone-refractory and metastatic prostate cancer, the significance of elevated PSMA expression in advanced prostate cancer has yet to be fully elucidated. We provide evidence that prostatic carcinoma cells expressing PSMA exhibit reduced motility and increased attachment when grown on a bone marrow matrix substrate. This phenomenon occurs via activation of focal adhesion kinase and provides the first evidence of a link between PSMA expression and prostate cancer metastasis to the bone. PMID- 17332930 TI - Involvement of Bcl-2 family members, phosphatidylinositol 3'-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. AB - Curcumin (diferulolylmethane), an active ingredient derived from the rhizome of the plant Curcuma longa, has anticancer activity in vitro and in vivo. Although curcumin possesses chemopreventive properties against several types of cancer, the molecular mechanisms by which it inhibits cell growth and induces apoptosis are not clearly understood. Our data revealed that curcumin inhibited growth and induced apoptosis in androgen-dependent and -independent prostate cancer cells, but had no effect on normal human prostate epithelial cells. Curcumin downregulated the expression of Bcl-2, and Bcl-XL and upregulated the expression of p53, Bax, Bak, PUMA, Noxa, and Bim. Curcumin upregulated the expression of p53 as well as its phosphorylation at serine 15, and acetylation in a concentration dependent manner. Acetylation of histone H3 and H4 was increased in cells treated with curcumin, suggesting histone modification may regulate gene expression. Treatment of LNCaP cells with curcumin resulted in translocation of Bax and p53 to mitochondria, production of reactive oxygen species, drop in mitochondrial membrane potential, release of mitochondrial proteins (cytochrome c, Smac/DIABLO and Omi/HtrA2), activation of caspase-3 and induction of apoptosis. Furthermore, curcumin inhibited expression of phosphatidyl-inositol-3 kinase (PI3K) p110 and p85 subunits, and phosphorylation of Ser 473 AKT/PKB. Downregulation of AKT by inhibitors of PI3K (Wortmannin and LY294002) and AKT, or by dominant negative AKT increased curcumin-induced apoptosis, whereas transfection of constitutively active AKT attenuated this effect. Similarly, wild-type phosphatase and tensin homolog deleted from chromosome 10 (PTEN) enhanced curcumin-induced apoptosis and, in contrast, inactive PTEN (G129E and G129R) inhibited curcumin-induced apoptosis. Overexpression of constitutively active AKT inhibited curcumin-induced p53 translocation to mitochondria, and Smac release to cytoplasm, whereas inhibition of AKT by dominant negative AKT enhanced curcumin-induced p53 translocation to mitochondria and Smac release. Our study establishes a role for AKT in modulating the direct action of p53 on the caspase-dependent mitochondrial death pathway and suggests that these important biological molecules interact at the level of the mitochondria to influence curcumin sensitivity. These properties of curcumin strongly suggest that it could be used as a cancer chemopreventive agent. PMID- 17332931 TI - Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis. AB - X-linked inhibitor of apoptosis protein (XIAP) is the most potent caspase inhibitory IAP family member and a negative regulator of various apoptotic stimuli. Thus, XIAP overexpression in cancer cells may select for tumor cell survival following various cytotoxic therapeutic modalities. The anatomical staging system in renal cell carcinoma (RCC) currently provides good prognostic information, albeit insufficient. We hypothesize that overexpression of XIAP in RCC may serve as a molecular prognostic marker in RCC and improve the staging of RCC. This study examined the protein level of XIAP in lysates from surgical specimens of 109 patients with RCC and 109 normal kidney specimens from the same patients. The level of XIAP expression was quantified by Western blot analysis using non-fixed fresh frozen tissues of RCCs and normal kidneys. Results indicated that the mean level of XIAP expression was higher in RCC compared to autologous normal kidney, and the XIAP expression level in 38/109 (35%) of RCC was more than 2-fold greater than that in normal kidney tissue. In Stage I/II RCC, the mean XIAP expression level was almost identical to that detected in normal kidney, whereas XIAP expression in Stage III/IV was 2.5-fold higher than that in Stage I/II RCC. Levels of XIAP expression also correlated with the grade of RCC. Patients with RCC with low XIAP expression had a longer postoperative disease-specific survival as compared to those with high expression in the 5-year follow-up. The suggested role of XIAP in the regulation of resistance in apoptosis was examined in vitro following treatment of RCC cell lines with XIAP antisense oligonucleotide and the cells were sensitized to both Fas-mediated and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. The present study demonstrates at the protein level that XIAP is overexpressed in RCC, and that high XIAP expression in RCC predicted a worse prognosis. In addition, XIAP antisense oligonucleotide sensitized RCC to Fas/TRAIL-induced apoptosis. These results suggest that XIAP expression in RCC may be used as a prognostic parameter, and that downregulation or inhibition of XIAP expression in RCC may reverse immune resistance. PMID- 17332932 TI - Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck. AB - The prodrug bivatuzumab mertansine (BIWI 1) is a novel CD44v6-targeting humanized monoclonal antibody coupled to the toxin mertansine. In a phase I dose escalation trial 31 patients with squamous cell carcinomas of the head and neck were treated with doses of 25-325 mg/m2 as a 30-min infusion. Thirteen patients received a second infusion after 3 weeks. Serial serum samples were collected to determine the pharmacokinetic parameters of the prodrug BIWI 1 and of deconjugated BIWI 1 as well as the occurrence of anti-BIWI 1 antibodies. The maximum tolerated dose was reached at 300 mg/m2 attributable to skin toxicity. No immune response was observed in any patient. For BIWI 1 and deconjugated BIWI 1, clearance values were low and distribution was limited resulting in half-lives of approximately 3 3.5 days and approximately 6-7 days, respectively, for single and repeated dosing after three weeks. Overall, interindividual variability of the pharmacokinetic parameters was low. In general, the pharmacokinetics of both compounds after single and repeated dosing was comparable across the entire dose range and no significant accumulation took place. Over the dose range investigated, a dose proportional increase in the exposure of BIWI 1 and deconjugated BIWI 1 was observed. Dose individualization according to body size (weight or body surface area) was found to be appropriate and is recommended for the novel immunoconjugate. PMID- 17332933 TI - Blockade of the vascular endothelial growth factor-receptor 2 pathway inhibits the growth of human renal cell carcinoma, RBM1-IT4, in the kidney but not in the bone of nude mice. AB - Primary and metastatic RCCs are consistently resistant to radiotherapy, chemotherapy, or immunotherapy. As recurrent or metastatic RCC after surgery is related with poor prognosis and cancer-related death, development of therapeutic modalities that can control RCC and improve patient survival is urgently needed. We determined whether blockade of the vascular endothelial growth factor-receptor 2 (VEGF-R2) signaling pathway inhibits the growth of human renal cell carcinoma cells in the kidney and bone of nude mice. Male nude mice implanted with 1x10(6) RBM1-IT4 cells in the kidney or in the tibia were treated with oral administrations of TSU-68, anti-VEGF-R2 tyrosine kinase inhibitor beginning 5 days after implantation. The tumor incidence, tumor weight and bone destruction were determined at twelve weeks after commencing the therapy. VEGF production by RCCs was determined by ELISA and alterations in VEGF production related with genetic instability were also analysed. VEGF-R expression of mouse osteoclast precursors (mOCPs) and human umbilical vascular endothelial cell (HUVEC) was determined by RT-PCR and Western immunoblotting. in vitro, the effects of TSU-68 on the cellular proliferation of HUVEC, normal human renal proximal tubule epithelial cell (RPTEC) and mOCPs were determined. RBM1-IT4 cells had loss of heterozygosity and frame shift mutation on chromosome 3p, inactivating the von Hippel-Lindau (VHL) tumor suppressor gene and resulting in the production of relatively higher levels of VEGF than the RCCs without VHL mutation. TSU-68 significantly inhibited the growth of RBM1-IT4 in the kidney (p<0.05). In contrast, TSU-68 did not inhibit the growth of RBM1-IT4 in the tibia or bone lysis. Although HUVEC, RPTEC and mOCPs expressed VEGF-R2, TSU-68 directly inhibited the VEGF-stimulated cell growth of HUVEC and RPTEC but not the mOCPs in vitro. These data indicate that the VEGF-VEGF-R2 pathway is not required for survival of the osteoclasts and anti-VEGF-R2 therapy did not contribute to the suppression of metastatic RCC growth in the bone. PMID- 17332934 TI - Dexamethasone as a chemosensitizer for breast cancer chemotherapy: potentiation of the antitumor activity of adriamycin, modulation of cytokine expression, and pharmacokinetics. AB - Dexamethasone (DEX) is mainly used as an anti-emetic agent in cancer therapy. We have recently demonstrated that DEX pretreatment increases the antitumor activity of the cancer chemotherapeutic agents carboplatin and gemcitabine, and decreases host toxicity in nude mouse xenograft models of human cancer. However, the underlying mechanisms are not fully understood. The present study was designed to determine the effects of DEX pretreatment on the anticancer activity of adriamycin (ADR) in a syngeneic model of breast cancer (4T1), emphasizing the effects of DEX on cytokine expression and modulation of ADR pharmacokinetics. We have demonstrated five major new findings about DEX pretreatment: a) it enhances the therapeutic effect of ADR, inducing almost complete inhibition of tumor growth; b) it increases tumor ADR accumulation; c) it modulates the expression of cytokines produced by the tumor, increasing TNFalpha and decreasing IL-1beta and VEGF expression; d) it enhances the effects of ADR on induction of apoptosis and inhibition of cell proliferation; and e) it suppresses nuclear NFkappaB activation and inhibits ADR-induced NFkappaB activation, possibly via IkappaB up regulation. These findings suggest that DEX can be used as a chemosensitizer and chemoprotectant. These results provide a rationale for the expanded clinical use of DEX for cancer therapy. PMID- 17332935 TI - A new comprehensive gene expression panel to study tumor micrometastasis in patients with high-risk breast cancer. AB - The incidence and prognostic relevance of bone marrow (BM) and leukapheresis (PBPC) tumor cell contamination (TCC) in breast cancer patients is still to be circumstantiated. We developed a new comprehensive gene expression panel to study cytokeratins (CK), maspin (MAS) and mammaglobin (MAM) as possible predictors of prognosis. Forty-eight patients undergoing high dose chemotherapy (HDCT) and PBPC support were enrolled and analyzed for TCC on 116 PBPC apheresis and 96 BM obtained at basal conditions. All of the patients were evaluated by reverse transcriptase nested PCR (RT-PCR) for MAM and MAS gene expression and by immunocytochemistry (ICC) and nested RT-PCR to evaluate CK expression. PBPC and BM frequency of CK-positive (+) cells was 12-13% by ICC and 71-73% by RT-PCR respectively. Sixty-seven percent of CK ICC+ samples were MAM RT-PCR+ and 89% of them were MAS RT-PCR+. PBPC and BM frequency of MAM+ cells was 21% and 31% respectively, while for MAS+ cells it was 48% and 52% respectively by RT-PCR. After 71 mo median FU, 16 patients (33%) relapsed and 14 (88%) had BM/PBPC TCC. No marker had an impact on overall survival (OS) but MAS expression on BM and MAM expression on PBPC correlated with a statistically significant improved (p=0.05) and worsened RFS (p=0.06) respectively. These data confirm the activity of MAM as a negative prognostic factor and show for the first time that MAS could work as a tumor suppressor gene even in a clinical setting, since it protects from recurrence. PMID- 17332936 TI - Combined effect of green tea and Ganoderma lucidum on invasive behavior of breast cancer cells. AB - Epidemiological studies have suggested that consumption of green tea may decrease the risk of a variety of cancers. In addition, mushroom Ganoderma lucidum has been used for the promotion of health, longevity and treatment of cancer in traditional Chinese medicine. In the present study we show that extract from green tea (GTE) increased the anticancer effect of G. lucidum extract (GLE) on cell proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of breast cancer cells. This effect was mediated by the down-regulation of expression of oncogene c-myc in MDA-MB-231 cells. Although individual GTE and GLE independently inhibited adhesion, migration and invasion of MDA-MB-231 cells, their combination demonstrated a synergistic effect, which was mediated by the suppression of secretion of urokinase plasminogen activator (uPA) from breast cancer cells. Our study suggests the potential use of combined green tea and G. lucidum extracts for the suppression of growth and invasiveness of metastatic breast cancers. PMID- 17332937 TI - Inhibition of the MAP kinase activity suppresses estrogen-induced breast tumor growth both in vitro and in vivo. AB - Elevated expression of mitogen-activated protein kinase (Erk/MAPK) has been noted in a significant percentage of primary human breast cancers. To directly assess the importance of Erk/MAPK activation in estrogen (E2)-induced tumor progression, we blocked E2-signaling with MEK-inhibitor CI-1040 and/or tamoxifen (Tam). Our data show that both MEK-inhibitor CI-1040 and Tam blocked E2-induced MAPK phosphorylation and cell proliferation in MCF-7 breast cancer cells in vitro. However, in vivo studies show that anti-tumor efficacy of combining the CI-1040 and Tam was similar to single agent(s). Furthermore, sequential treatment with Tam followed by CI-1040 or CI-1040 followed by Tam did not significantly reduce E2-induced tumor growth. This suggests that the combination of CI-1040 and Tam may not be synergistic in inhibiting E2-induced tumor growth. However, these findings also indicate that MAPK plays a critical role in E2-induced tumor growth, and that this could be a potential therapeutic target to combat hormonally regulated growth in ER-positive tumors. PMID- 17332938 TI - Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression. AB - Leukemia inhibitory factor (LIF) is a pleiotrophic cytokine, which plays an important role in inducing cancer cachexia. We have previously reported that LIF promotes cell proliferation in some human carcinoma cells through c-fos, jun-B and cyclin-E expression. In the present study, we analyzed the regulation of LIF and its receptor (LIFR) expression in pancreatic carcinoma cells. Seven pancreatic carcinoma cells expressed constitutively LIF and its heterodimer receptor (LIFR and gp130) mRNA in RPMI-1640 medium without FBS. The amount of LIF immunoreactive protein was 132.5+/-52 pg/10(6) cells in culture supernatants without FBS. Pro-inflammatory cytokines, such as TNF-alpha, IL-1beta, IL-6, IL-8, or LIF, enhanced the expression of LIF mRNA in Hs-700T and Hs-766T cells. Addition of LIF significantly induced cell proliferation of Hs700T in 13 days LIF dose-dependently. However, anti-LIF IgG failed to suppress cell proliferation in Hs-700T cells. LIF acted as a paracrine growth factor in Hs-700T cells, which expressed low amount of LIF without stimuli. Cellular signal transductions by LIF was down-regulated by inhibitors of protein kinase C (PKC), protein tyrosine kinase (PTK), and Ca/Calmodulin. LIF induced phosphorylation of STAT3. Moreover, exogenous LIF upregulated the expression of LIFR mRNA. Antisense LIFR oligonucleotide significantly suppressed cell growth in the presence of LIF in Hs 700T cells. These results suggest that cytokine network might alter the expression and responsiveness to LIF in tumor microenvironment. PMID- 17332939 TI - MMP-9-hemopexin domain hampers adhesion and migration of colorectal cancer cells. AB - Matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are involved in colon cancer progression and metastasis due to their ability to degrade extracellular matrix (ECM) components. In previous studies we described the MMP-9 hemopexin like domain (MMP-9-PEX) as an MMP-9 antagonist. In the present study it was examined whether recombinant MMP-9-PEX has an inhibitory effect on migration and adhesion of colorectal carcinoma cells. Furthermore, we searched for MMP-9 substrate binding sites within the MMP-9-PEX by surface plasmon resonance. Migration of SW620 and LS174 cells was investigated in a modified Boyden chamber assay. In the presence of 0.2 microg/ml MMP-9-PEX migration of SW620 was decreased by 34%, while addition of 0.4 microg/ml diminished migration by 56%. Migration of LS174 cells was not affected by MMP-9-PEX. Adhesion studies were performed on 96-well plates coated with gelatin, collagen type I, and laminin, respectively. In the presence of MMP-9-PEX, adhesion of SW620 cells to these coating substrates was significantly inhibited. Surface plasmon resonance studies revealed binding of collagen type I and IV, elastin, and fibrinogen to proMMP-9 as well as to MMP-9-PEX. However, equilibrium constants (Kd) indicated a higher affinity of proMMP-9 to the matrix proteins. This could indicate that there is more than one binding site for matrix components within the entire proMMP-9 molecule. Since migration and adhesion of metastatic colorectal carcinoma cells were reduced by MMP-9-PEX, this recombinant MMP-9 antagonist might be of therapeutical interest. PMID- 17332940 TI - Arsenic trioxide induces p53-dependent apoptotic signals in myeloma cells with SiRNA-silenced p53: MAP kinase pathway is preferentially activated in cells expressing inactivated p53. AB - Mutations in p53 are the most common genetic abnormality in cancers. Arsenic trioxide (ATO) is an effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia (APL) and is being tested in phase II studies in various types of cancers. We have shown that ATO is a potent inducer of apoptosis in multiple myeloma cells, engaging primarily the intrinsic apoptotic pathway in cells expressing w.t. p53 and the extrinsic apoptotic pathway in cells expressing mutant p53. To further establish the differential apoptotic signals of ATO in relation to p53 functional status we studied the activation of the intrinsic and the extrinsic apoptotic pathways in IM9 myeloma cells expressing w.t. p53 following silencing of p53 and p21 with the corresponding SiRNAs-GFP constructs. In untransfected cells or in cells transfected with GFP-empty vector construct we observed weak apoptosis concomitant with mild depolarization of mitochondrial membrane, depletion of reduced glutathione and release of cytochrome c. Following silencing of p53 or p21 we observed extensive apoptosis concomitant with extensive depolarization of mitochondrial membrane and depletion of reduced glutathione. We also observed in these cells activation of the extrinsic apoptotic pathway through upregulation of APO2/TRAIL and APO2/TRAIL-R2, activation of caspase 8, degradation of FLIP-L and release of apoptosis inducing factors from mitochondria, instead of cytochrome c. In addition, we observed marked activation of the MAP kinase pathway and dephosphorylation of Akt in p53 or p21 silenced cells. Hence, silencing of p53 or p21 in IM9 myeloma cells results in diversion of apoptosis to the extrinsic pathway and sensitization of myeloma cells to ATO. PMID- 17332941 TI - Differential modulation of nuclear texture, histone acetylation, and MDR1 gene expression in human drug-sensitive and -resistant OV1 cell lines. AB - Image cytometric study of pathological specimens or cell lines has suggested that epigenetic mechanisms are likely to play a major role in determining chromatin patterns evaluable through nuclear texture analysis. We previously reported that nuclear textural changes observed in the OV1-VCR etoposide-resistant ovarian carcinoma cell line were associated with an increased acetylated histone H4 level. In this study we analyzed the effects of treatments with the HDAC inhibitor trichostatin A (TSA) or with nickel subsulfide on histone H4 acetylation, nuclear texture, and MDR1 gene expression in drug-sensitive IGROV1 and drug-resistant OV1-VCR cell lines. In IGROV1 cells, TSA induced an increase in acetylated H4 level associated with a chromatin textural decondensation and an increase in MDR1 gene expression. In OV1-VCR cells, a similar increase in H4 acetylation was observed, but nuclear texture or MDR1 gene expression remained unchanged. ChIP analysis revealed that MDR1 gene expression remained stable in TSA-treated OV1-VCR cells despite a localized increase in H4 acetylation at the promoter level. Analysis of the methylation status of MDR1 promoter showed an increase in DNA methylation at 3 specific sites in OV1-VCR cells, that could participate to TSA low responsiveness in these cells. Treatment with nickel subsulfide induced a decrease in H4 acetylation without any effect on nuclear texture characteristics in both cell lines. In OV1-VCR cells, nickel subsulfide induced a significant down-regulation of the MDR1 gene expression. These results indicate that modulation of histone H4 acetylation level can be associated with up- or down-regulation of the MDR1 gene in OV1 cells. However, this modulation does not always result in chromatin pattern alterations and these data emphasize the complexity of chromatin texture regulation in tumor cells. PMID- 17332942 TI - Immunization with MHC class I-negative but not -positive HPV16-associated tumour cells inhibits growth of MHC class I-negative tumours. AB - Loss or downregulation of MHC class I molecules on tumour cells is a common mechanism by which tumours can escape from T-cell mediated immune responses. In this study we have investigated the immunologic crossreactivity between murine tumour cell lines expressing human papilloma virus (HPV) 16-derived E6/E7 oncoproteins with distinct surface expression of MHC class I molecules. The aims of this study were to demonstrate whether immune responses capable of coping with MHC class I-positive tumours can also be effective against their MHC class I deficient derivatives and whether it is possible to induce immunity against MHC class I-deficient tumours by cellular vaccines based on MHC class I-deficient tumour cell lines. Our data showed that immunization with MHC class I-deficient but not with MHC class I positive tumour cells inhibited the growth of MHC class I-deficient tumours. In vivo depletion studies revealed that the mechanisms underlying effective immune responses against MHC class I-negative tumours in animals immunized with MHC class I-deficient tumour cells involved natural killer cells. The presented findings are of particular clinical relevance in the sense of construction of vaccines directed against a broad spectrum of HPV-associated tumours. PMID- 17332943 TI - Alterations of EGFR/HER, angiogenesis and apoptosis pathways after therapy with antagonists of growth hormone releasing hormone and bombesin in non-small cell lung cancer. AB - New therapeutic strategies are necessary to improve the treatment of lung cancer. We investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonist, RC-3940-II, and growth hormone-releasing hormone (GHRH) antagonists, MZ-J-7-114 and MZ-J-7-118, on the expression of epidermal growth factor receptor (EGFR)/HER (-2, -3, and -4) family, angiogenic factors, VEGF-A and VEGF receptors (VEGF-R1 and VEGF-R2), and the apoptotic molecules Bax and Bcl-2, in H-460 and A 549 non-small cell lung carcinomas (NSCLC). Nude mice bearing xenografts of H-460 and A-549 NSCLC were treated daily with these peptide analogues for 4 weeks. The treatment resulted in growth inhibition of H-460 by 22-77% and A-549 NSCLCs by 64 84%. The inhibition of tumor growth was associated with a down-regulation of members of EGFR/HER family. A significant reduction of the levels of expression of EGFR/HER family on both tumors varied from 29-96%: the greatest inhibition being induced by RC-3940-II. Similarly, a significant decrease in the levels of VEGF-A in tumors by 19-60% and VEGF receptors (VEGF-R1, 24-74% and VEGF-R2, 25 50%) was detected after therapy. An up-regulation of Bax by 21-63% and a down regulation of Bcl-2 by 23-39% was observed only for H-460 NSCLC. Our study demonstrates that human H-460 and A-549 NSCLC, express receptors for GHRH and bombesin/GRP, and respond to the respective antagonists. The antagonists of bombesin/GRP and GHRH could provide a new strategy for treatment of NSCLC through down-regulation of EGFR/HER family and an interference with the angiogenic and apoptotic pathways. PMID- 17332944 TI - A case of Lhermitte-Duclos disease presenting high FDG uptake on FDG-PET/CT. AB - Lhermitte-Duclos Disease (LDD) is a rare cerebellar lesion that has long been controversial as to whether the entity is a hamartoma, a malformation, or a neoplasm. Recent advances in metabolic imaging and molecular biology have unveiled biological features of LDD and a close relationship between LDD and Cowden disease. Adult onset LDD is now considered identical to Cowden disease in a US guideline. We present a case of LDD, in which high fluorodeoxy glucose (FDG) uptake was shown on PET/CT. We performed dual time point scans, in which a delayed scan exhibited more intense FDG uptake by the hamartomatous lesion than an early scan. We must remain aware of the possibility of LDD when intense accumulation is observed in a cerebellar lesion on FDG-PET/CT imaging. PMID- 17332945 TI - Durable response of a radiation-induced, high-grade cerebellar glioma to temozolomide. AB - BACKGROUND: Radiation-induced high-grade gliomas are a rare but serious late complication of radiotherapy. We report a patient with radiation-induced cerebellar high-grade glioma who had a durable response to temozolomide. PATIENTS AND METHODS: Case report of a 77-year-old woman with a radiation-induced, high grade cerebellar glioma that responded durably to temozolomide. RESULTS: Our patient developed a cerebellar high-grade glioma 9 years after treatment for a stage IV (T4N0M0) supraglottic laryngeal squamous cell carcinoma with cisplatinum and fluorouracil chemotherapy, and subsequently focal head and neck radiotherapy. Patient was treated with radiation and concurrent temozolomide (only partially due to toxicity) and was stable for 1 year without further adjuvant treatment. Subsequently the tumor recurred and the patient had a dramatic and durable response to standard 5 day dosing of adjuvant temozolomide. CONCLUSION: High grade gliomas are a late complication of radiation to the central nervous system and may respond to chemotherapy. PMID- 17332946 TI - Treatment of CNS dissemination in systemic lymphoma. AB - The frequency of central nervous system (CNS) dissemination in non-Hodgkin's lymphoma (NHL) varies and is dependent on NHL histology. More than 50% of patients with CNS involvement have advanced and progressive systemic disease. While CNS involvement at initial diagnosis may be treated curatively, treatment of CNS involvement in systemic relapsing or refractory lymphoma is challenging and most often palliative. Due to a paucity of randomized trials, treatment of lymphomatous metastases is not standardized. Nonetheless, treatment of LM entails administration of both CNS-directed and systemic chemotherapy that often includes high-dose chemotherapy regimens with stem cell support. PMID- 17332948 TI - Malignant astroblastoma with rhabdoid morphology. PMID- 17332947 TI - Intracranial solitary juvenile xanthogranuloma successfully treated with stereotactic radiosurgery. AB - Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, which primarily affects the skin in young children. Although intracranial involvement is rare, it differs from other systemic JXG because its responsiveness to non surgical treatment is poor. We present the case of a 2-year-old boy with left abducens nerve palsy. Imaging studies revealed a mass in the left Meckel's cave. Systemic examination showed no other abnormalities including his skin. After partial removal, JXG was diagnosed based on immunohistochemical evaluation. He underwent a stereotactic radiosurgery. Then, the mass decreased, and his abducens nerve palsy improved. This is the seventh case with isolated intracranial JXG, and the first case to be treated with radiosurgery. We consider that stereotactic radiosurgery is an excellent choice for treatment of intracranial JXG. PMID- 17332949 TI - Aggressive lymphoma involving intracranial epidural region. PMID- 17332950 TI - Embryonal tumor with abundant neuropil and true rosettes (ETANTR): report of a case with prominent neurocytic differentiation. AB - We report a case of a 2 year-old boy who initially presented with macrocephaly and severe global developmental delay. Imaging revealed a large left temporo parietal mass that was lobulated, calcified, focally enhancing and partially cystic. A second surgery was required for tumor recurrence approximately one year later, and tissue from that resection proved to be diagnostic for an embryonal tumor with abundant neuropil and true rosettes (ETANTR). Only 12 cases of this rare pediatric embryonal tumor have been previously documented, and as of 2000, the WHO has not recognized ETANTR as a distinct entity (Kleihues P, Cavenee WK (2000) International agency for research on cancer: pathology and genetics of tumors of the nervous system. IARC Press, Lyon). As opposed to prior cases, our patient's tumor exhibited extensive neurocytic elements. Two recently described cases were examined via fluorescence in situ hybridization (FISH), with one demonstrating isochromosome 17q (i17q) and the second exhibiting polysomies of chromosomes 2, 8, 17 and 22 (Fuller C, Fouladi M, Gajjar A, Dalton J, Sanford RA, Helton KJ (2000) Am J Clin Pathol 126: 277-283). Via FISH analysis, we found normal dosages of chromosomes 2, 8 and 17. Our case expands the histopathologic spectrum of ETANTR, illustrating marked neuronal differentiation towards neurocytes. The lack of common PNET-associated FISH abnormalities in this case adds to the limited cytogenetic genetic data on this rare pediatric embryonal neoplasm. PMID- 17332952 TI - Endoscopic transmural entry into pancreatic fluid collections using a dedicated aspiration needle without endoscopic ultrasound guidance: success and complication rates. AB - BACKGROUND: Endoscopic drainage of pancreatic fluid collections (PFC) is performed with increasing frequency. A variety of techniques for performing transmural entry have been described. However, data are lacking on the technical success and safety of transmural entry using a single technique. The authors describe the largest experience in transmural entry of PFCs without endoscopic ultrasound (EUS) guidance using a dedicated aspiration needle. METHODS: All patients who underwent endoscopic transmural drainage of PFC from October 1998 to May 2006 were identified from the endoscopy database. Data were abstracted from the endoscopic procedure report and the patient records then placed in a JMP drive. All drainages were performed without EUS guidance after visualization of an obvious intraluminal bulge using a dedicated large-bore aspiration needle. The transmural tract into the PFC was dilated using a balloon with a diameter of 6 to 20 mm followed by subsequent placement of one or two 10-Fr double pigtail stents with or without nasocystic irrigation tubes. Successful entry was defined as entry allowing for the placement of stents. RESULTS: No significant difference in the complication rates was observed when they were analyzed for the following variables: age, gender, balloon diameter, presence of endoscopic impression, drainage approach, and size and type of fluid collection. CONCLUSION: Endoscopic transmural drainage of pancreatic fluid collections can be performed safely and effectively via the Seldinger technique without endoscopic ultrasound guidance. The study data will allow sample size calculations to be made if direct comparisons with this technique and others are undertaken. PMID- 17332953 TI - Size matters: gastric pouch size correlates with weight loss after laparoscopic Roux-en-Y gastric bypass. AB - BACKGROUND: Over the past 20 years, there has been an ongoing discussion about the importance of gastric pouch size as a key factor influencing weight loss after bariatric surgery. This analysis aimed to determine the relationship between initial gastric pouch size and excess weight loss (EWL) after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Between August 2002 and March 2005, 320 LRYGB were performed at Yale New Haven Hospital. The patients' demographics were entered into a longitudinal, prospective database. Upper gastrointestinal series were routinely performed on postoperative day 1. Pouch size was measured as area (cm2) on an anteroposterior radiograph at maximum pouch distention. Linear regression analysis was performed to determine the association between pouch size and weight loss at 6 and 12 months postoperatively. Adjustments were made for age, gender, and preoperative body mass index (BMI). RESULTS: The mean age of the patients was 41.2 years. Of the 320 study patients, 261 were women (81.6%) and 59 were men (18.4%). The mean preoperative BMI was 51.1 kg/m2; the mean 6-month EWL was 50.5%; the mean 12-month EWL was 62.5%; and the mean pouch size was 63.9 cm2. A statistically significant, negative correlation between pouch size and EWL was found at 6 months (beta = -0.241; p < 0.01) and at 12 months (beta = -0.302; p < 0.02). The findings show that male gender (beta = 0.147; p < 0.04) and preoperative BMI (beta = 0.190; p < 0.01) are positively correlated with pouch size. CONCLUSION: The analysis demonstrates that initial gastric pouch size is not the only significant component for successful weight loss after LRYGB. Male gender and increased preoperative BMI were identified as factors predicting pouch size. Efforts to standardize small pouch size for all patients seems important to the success of surgical therapy for morbid obesity. PMID- 17332954 TI - Development of a perfused ex vivo tumor-mimic model for the training of laparoscopic radiofrequency ablation. AB - BACKGROUND: Laparoscopic radiofrequency ablation (RFA) is a safe and effective method for tumor destruction in patients with unresectable liver tumors. However, accurate probe placement using laparoscopic ultrasound guidance is required to achieve complete tumor ablation. This study aimed to develop a perfusable ex vivo tumor-mimic model for laparoscopic radiofrequency ablation training. METHODS: After rinsing the prepared liver vessels with anticoagulants, porcine livers were perfused. Tumor-mimics were created by injecting a mixture consisting of 3% agarose, 3% cellulose, 7% glycerol, and 0.05% methylene blue, creating hyperechoic lesions in ultrasound. Heparinized porcine blood was used as perfusion medium. Continuous perfusion of the porcine liver was provided by connection of a pump system to the portal vein and the vena cava inferior. Laparoscopic RFA techniques were taught using a laparoscopic pelvi-trainer. RESULTS: A total of 30 laparoscopic ablations were performed in four porcine livers. The simulated "tumors" were clearly visible on laparoscopic ultrasound and not felt during placement of the RFA probe. In addition, color duplex ultrasound showed clear signals indicating for a sufficient liver perfusion. CONCLUSION: Laparoscopic RFA requires advanced laparoscopic ultrasound skills for an accurate placement of the RFA probe. The perfused tumor-mimic model presented is a safe, easy, effective, and economic method to improve and train laparoscopic RFA skills on porcine liver tissue. PMID- 17332955 TI - An experimental sheep model used to develop an ablation procedure for chronic atrial fibrillation. AB - BACKGROUND: Atrial fibrillation is the most common form of serious arrhythmia in humans. The therapeutic options offered are medical, surgical, and interventional. The surgical approach is justified in cases of atrial fibrillation already subjected to cardiac surgery for an associated organic heart disease such as a valvular or ischemic disease. A minimally invasive surgical approach is needed to extend the possibility of surgical treatment to patients with lone atrial fibrillation and those who cannot be treated by interventional procedures. This study aimed to use sheep as an experimental model in developing a minimally invasive surgical procedure for chronic atrial fibrillation therapy in humans. METHODS: The investigation was conducted with 20 animals using a video assisted thoracoscopic approach, in which a flexible microwave energy ablating probe was positioned on the epicardial surface encircling the pulmonary veins. RESULTS: In 10 of the 20 animals, it was possible to encircle the pulmonary veins using the thoracoscopic approach in less than 3 h without major complications. CONCLUSION: The epicardial ablation procedure using the thoracoscopic approach is feasible, safe, and reproducible. PMID- 17332956 TI - Laparoscopic vs. open surgery for acute adhesive small-bowel obstruction: patients' outcome and cost-effectiveness. AB - BACKGROUND: Numerous studies have demonstrated the feasibility of laparoscopy in the management of acute adhesive small-bowel obstruction (AASBO). However, comparative data with laparotomy are lacking. The aim of this study was to compare laparoscopy and laparotomy for the treatment of AASBO in terms of patient outcome and cost-effectiveness. METHODS: A retrospective chart review of all patients who underwent surgery for AASBO from 1999 to 2005 was conducted. Data recorded included operative and postoperative course, among others. Operative and total hospital charges were estimated from the Patient Accounting System. RESULTS: Thirty-one patients who underwent laparoscopy were matched to a similar group of patients who underwent laparotomy. In the laparoscopy group, four patients (13%) had a laparoscopy-assisted procedure and ten patients (32%) were converted. The laparoscopy group was subdivided into laparoscopy, laparoscopy assisted, converted, and assisted-converted subgroups. In the majority of the patients, AASBO was secondary to a single band. Overall morbidity was significantly higher in the laparotomy group (p = 0.007). Morbidity rates were statistically significant between the laparoscopy and assisted-converted subgroups (p = 0.0001) but not between the laparotomy group and assisted converted subgroup (p = 0.19). Median hospital stay and median time to first bowel movement were significantly shorter in the laparoscopy group. Charge data were available for only the last three years of the study. Operative charges and total hospital charges were similar between the laparoscopy and the laparotomy groups (p = 0.14 and p = 0.10, respectively). There was a significant difference in total hospital charges between the laparoscopy subgroup and laparotomy group (p = 0.03). CONCLUSIONS: Laparoscopy for AASBO is associated with reduced hospital stay, early recovery, and decreased morbidity. Laparoscopy-assisted and converted surgeries do not differ significantly from laparotomy in regard to patient outcome. Operative and total hospital charges are similar for both laparoscopy and laparotomy. PMID- 17332957 TI - A comparison between fluoroscopically guided radiofrequency energy delivery and conventional technique in an animal model of fundoplication failure. AB - BACKGROUND: The use of radiofrequency energy (RFe) treatment at the gastroesophageal junction (GEJ) has been considered an alternative to surgery after fundoplication disruption. It is unknown whether the recommended delivery technique for primary gastroesophageal reflux disease applies to an anatomically altered GEJ following fundoplication. The aim of this study was to determine whether modifications to the standard technique using fluoroscopic guidance more accurately localizes ablation zones compared with standard technique alone. METHODS: Ten pigs were randomized to either conventional or fluoroscopically guided RFe ablation. All pigs had a laparoscopic Nissen fundoplication that was subsequently disrupted by severing all but the most cranial fundoplication stitch. Conventional RFe delivery included usage of markers located on the Stretta catheter. After labeling the z-line via submucosal contrast injection, fluoroscopic guidance involved using fluoroscopic markers to guide RFe ablation. Ablations were acutely marked, measured, and agreed upon by a panel of three researchers analyzing harvested tissue. Distances from the target zone for each ablation line (e.g., 1 cm was the target zone for line 1) were calculated and analyzed using Mann-Whitney and Fischer's tests. RESULTS: Fluoroscopic guidance was significantly more accurate than the conventional technique (0.2 +/- 0.2 cm vs. 1.8 +/- 0.8 cm, p < 0.0001). Analyzing the individual distances for each of the six ablation lines revealed that all within Group B were closer than Group A (p < 0.01 for all except lines 1 and 2). Overall, the total ablation treatment length for conventionally treated animals was 4.48 +/- 0.7 cm and for those who underwent fluoroscopic guidance it was 2.92 +/- 0.5 cm (p < 0.001). CONCLUSION: In a porcine model of fundoplication disruption, fluoroscopic guidance improved RFe accuracy. PMID- 17332958 TI - A reliable method for handling the "difficult" cystic duct to obtain a good cholangiogram during laparoscopic cholecystectomy. AB - BACKGROUND: Intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC) is used to assess the anatomy of the biliary tree and to detect any stones contained within it. Intraoperative cholangiography may be performed either routinely or more selectively in cases where there is a high suspicion of choledocholithiasis or for those patients whose anatomy appears unclear at operation [8]. In cases where significant inflammation is present, the cystic duct may be short, thickened, or dilated and thus difficult to manipulate to obtain a satisfactory IOC. METHODS: We describe a safe, simple, reliable technique to control the "difficult" cystic duct during IOC with a vascular vessel loop instead of a surgical clip to obtain good control and avoiding extravasation of dye during IOC. The feasibility, safety, and results of this technique are described. RESULTS: During a 1-year period, this technique has been used in 10 patients, and it was successful in all attempted cases, with a good quality IOC obtained on the first attempt. The cystic duct was then occluded in all cases using a Vicryl "0" endoloop. One patient had a common bile duct stone and this patient received postoperative endoscopic retrograde pancreatography (ERCP). All patients were discharged home with no complications. In cases where a short, thickened, or dilated cystic duct was present, ductal control during IOC was easily obtained using a vascular vessel loop. CONCLUSIONS: This is a safe, reliable, less traumatic, readily available, and inexpensive method that provides a secure way of handling the "difficult" cystic duct. PMID- 17332959 TI - Robot-assisted laparoscopic surgery of the infrarenal aorta : the early learning curve. AB - BACKGROUND: Recently introduced robot-assisted laparoscopic surgery (RALS) facilitates endoscopic surgical manipulation and thereby reduces the learning curve for (advanced) laparoscopic surgery. We present our learning curve with RALS for aortobifemoral bypass grafting as a treatment for aortoiliac occlusive disease. METHODS: Between February 2002 and May 2005, 17 patients were treated in our institution with robot-assisted laparoscopic aorto-bifemoral bypasses. Dissection was performed laparoscopically and the robot was used to make the aortic anastomosis. Operative time, clamping time, and anastomosis time, as well as blood loss and hospital stay, were used as parameters to evaluate the results and to compare the first eight (group 1) and the last nine patients (group2). RESULTS: Total median operative, clamping, and anastomosis times were 365 min (range: 225-589 min), 86 min (range: 25-205 min), and 41 min (range: 22-110 min), respectively. Total median blood loss was 1,000 ml (range: 100-5,800 ml). Median hospital stay was 4 days (range: 3-57 days). In this series 16/18 anastomoses were completed with the use of the robotic system. Three patients were converted (two in group 1, one in group 2), and one patient died postoperatively (group 1). Median clamping and anastomosis times were significantly different between groups 1 and 2 (111 min [range: 85-205 min] versus 57.5 min [range: 25-130 min], p < 0.01 and 74 min [range: 40-110 min] versus 36 min [range: 22-69 min], p < 0.01, respectively) Total operative time, blood loss, and hospital stay showed no significant difference between groups 1 and 2. CONCLUSIONS: Robot-assisted aortic anastomosis was shown to have a steep learning curve with considerable reduction of clamping and anastomosis times. However, due to a longer learning curve for laparoscopic dissection of the abdominal aorta, operation times were not significantly shortened. Even with robotic assistance, laparoscopic aortoiliac surgery remains a complex procedure. PMID- 17332960 TI - Prone thoracoscopic esophageal mobilization for minimally invasive esophagectomy. AB - BACKGROUND: Minimally invasive esophagectomy is a complex surgical procedure. We recently began performing thoracic mobilization of the esophagus with the patient in the prone position, not the left lateral decubitus position, in the hope of minimizing the number of technical challenges. METHODS: Six consecutive minimally invasive esophagectomies were performed using prone thoracoscopic esophageal mobilization with creation of cervical anastamosis. Our esophagectomy database was evaluated for outcomes, including operative time, estimated blood loss, complications, and length of hospital stay. RESULTS: We were successful in our first six attempts, with a mean blood loss of 61 cc. Mean operative time for thoracoscopy was 80 min. Operative times were steady over the first six prone cases at 105, 85, 70, 55, 80, and 85 min. Three of the six patients had no complications. Median postoperative length of hospital stay was 11.5 days, and there were no deaths. CONCLUSIONS: This technical report and case series demonstrates that prone thoracoscopic esophageal mobilization appears to be a reasonable alternative to the same procedure performed with the patient in the decubitus position. We find the technique to simplify portions of an otherwise difficult surgical procedure. Further evaluation with larger number of patients should be performed. PMID- 17332961 TI - The effect of a low-carbohydrate diet on the nonalcoholic fatty liver in morbidly obese patients before bariatric surgery. AB - BACKGROUND: Bariatric surgery may be complicated by enlargement of the liver, especially of the left lobe, caused by nonalcoholic fatty liver disease often present with morbid obesity. METHODS: The effect of a very low carbohydrate diet for 4 weeks before surgery on liver density and volume was assessed in 14 candidates for bariatric surgery. Computed tomography (CT) scans were performed before and at termination of the diet period. RESULTS: The CT scans clearly showed a significant increase in mean liver density (p = 0.06) and a decrease in mean liver volume (p = 0.01). The increased mean density of the left lobe was markedly greater than that of the right lobe. CONCLUSIONS: The findings show that 4 weeks of a very low carbohydrate diet reduces liver fat content and liver size, particularly of the left lobe. This approach may render bariatric surgery or any foregut operations less difficult in morbidly obese patients and may be a useful treatment for nonalcoholic fatty liver disease. PMID- 17332962 TI - Coagulation status and the presence of postoperative deep vein thrombosis in patients undergoing laparoscopic cholecystectomy. AB - BACKGROUND: Venous thromboembolism is a relevant social and health care problem because of its high incidence among patients who undergo surgery (20-30% after general surgical operations and 50-75% after orthopedic procedures), its pulmonary embolism-related mortality rate, and its long-term sequelae (postthrombotic syndrome and ulceration), which may be disabling. This study aimed to determine the coagulation status and the presence of postoperative deep vein thrombosis (DVT) in patients undergoing laparoscopic (LC) and open cholecystectomy (OC). METHODS: Prospectively, 114 patients were randomized into two groups. group 1 (58 patients undergoing LC) and group 2 (56 patients who are undergoing OC). The coagulation parameters (prothrombin time [PT], partial thromboplastin time [PTT], D-dimer, prothrombin F1 + 2, antithrombin III, and factor VII) were monitored preoperatively and during the operation, then 24 and 72 h after the operation. The patients in both groups underwent color duplex scan examination preoperatively, then 3 and 7 days after surgery to establish the presence of DVT. None of the patients in either group received thrombosis prophylaxis. RESULTS: In the LC group, postoperative DVT developed in four patients (6.9%; in the calf veins of 3 patients and in the popliteal vein of 1 patient). In the OC group, nine patients (16.07%) had postoperative DVT (in the calf veins of 7 patients and in the popliteal and femoral veins of 2 patients). The plasma levels of monitored parameters in the patients of both groups were altered, but the difference between the groups was not statistically significant. For the patients in both groups who experienced DVT, only the decrease of factor VII had statistical significance (p < 0.05). CONCLUSIONS: The incidence of postoperative DVT among the patients who underwent OC was higher than among the patients who underwent LC (p < 0.05). The decrease in factor VII among the patients who underwent surgery could be a potentially useful parameter indicating the patients at high risk for developing DVT. PMID- 17332963 TI - Intraoperative endoscopic pneumatic testing for gastrojejunal anastomotic integrity during laparoscopic Roux-en-Y gastric bypass. AB - BACKGROUND: Gastrojejunal anastomotic leaks remain a major source of morbidity following laparoscopic gastric bypass. Intraoperative pneumatic testing has been offered as a method to reduce the incidence of this complication. This study's purpose was to assess the efficacy of intraoperative pneumatic testing during laparoscopic gastric bypass, to evaluate the types of air leaks detected, and to develop an algorithm for management that takes into account air leak categorization and drainage. METHODS: A retrospective analysis was performed on the initial 257 consecutive patients undergoing laparoscopic gastric bypass by a single surgeon over a 36-month period. The gastrojejunostomy was constructed using a linear stapler technique. All patients underwent intraoperative endoscopic pneumatic testing with a clamp applied to the Roux limb. All patients underwent water-soluble upper gastrointestinal radiography on the first postoperative day. RESULTS: Patients were divided based on the pneumatic testing results into groups for data analysis: persistent air leak (group 1), non reproducible air leak (group 2), and no air leak (group 3). The overall age (41.7+/-9.3 years), body mass index (BMI) (47.3+/-6.4 kg/m2), conversion rate (2%), and length of stay (1.9+/-2.0 days) were not statistically different among groups (p>0.05). In group 1, the air leak site was repaired, and 11 (92%) were drained. In group 2, the air leak site could not be identified, and all 12 (4.7%) were treated by drainage alone. In group 3, drains were placed in 12 (5.2%) due to difficult construction of the gastrojejunostomy. Overall postoperative gastrointestinal leak rate was 0.78%. No postoperative clinical or radiological gastrointestinal leaks occurred within the region tested pneumatically. Intraoperative complications related to pneumatic testing occurred in 1 (0.39%) patient. CONCLUSIONS: Intraoperative pneumatic testing of the gastrojejunal anastomosis is a safe and rapid means of evaluating anastomotic integrity. Application of this technique permitted timely repair of flawed anastomoses, thereby averting potential postoperative leaks. PMID- 17332964 TI - Long-term outcomes confirm the superior efficacy of extended Heller myotomy with Toupet fundoplication for achalasia. AB - BACKGROUND: The standard Heller myotomy (SM) for achalasia extends 1 to 2 cm on to the stomach. The authors perform an extended myotomy (EM) (>3 cm) with the goal of reducing postoperative dysphagia. This study examines the long-term efficacy and durability of EM compared with SM. METHODS: Patients with achalasia who underwent a laparoscopic Heller myotomy were identified from a prospective database that includes symptom evaluation and results of esophageal functional studies. From September 1994 to August 1998, the authors performed SM with Dor fundoplication, and from September 1998 through 2003, they performed EM with Toupet fundoplication. In 2001, they performed a telephone survey of all available patients. This was repeated in 2005 for the EM group. The survey included scales of symptom frequency (0 [never], 1 [once per month], 2 [once per week], 3 [once per day], 4 [more than once per day]) and severity (0 [no symptoms] to 10 [symptoms equal to preoperative state]) as well as the need to undergo postoperative intervention for dysphagia. RESULTS: For this study, 52 patients underwent SM with Dor fundoplication (median follow-up period, 46 +/- 24 months), and 63 patients underwent EM with Toupet fundoplication (median follow up period, 45 +/- 17 months. Postoperative dysphagia severity was significantly better in the EM group (4.8 +/- 2.3 vs 3.1 +/- 2.6; p < 0.005). There was no significant difference in postoperative heartburn frequency, esophageal acid exposure, or lower esophageal sphincter pressure. In the SM group, 9 patients (17%) required reintervention for dysphagia: 14 endoscopic interventions for 5 patients (10%) and reoperation for 4 patients. Three patients (5%) in the EM group required reintervention for dysphagia: one endoscopic intervention each and no reoperations (p < 0.05). A total of 30 patients in the EM group were contacted in both 2001 (median follow-up period, 19 +/- 11 months) and 2005 (median follow up period, 63 +/- 10 months). There was no significant change over time in dysphagia severity (2.6 +/- 1.9 vs 3.7 +/- 2.0; p = 0.19). CONCLUSIONS: For the treatment of achalasia, EM with Toupet fundoplication provides excellent durable dysphagia relief that is superior to SM with Dor fundoplication. PMID- 17332965 TI - Peritoneal transforming growth factor beta-1 expression during laparoscopic surgery: a clinical trial. AB - BACKGROUND: Transforming growth factor-beta 1 (TGF-beta1) is a growth factor involved in various biologic processes, including peritoneal wound healing and dissemination of malignancies. Laparoscopic surgery is evolving rapidly, and indications are increasing. The peritoneal TGF-beta1 expression during laparoscopic surgery is unknown. METHODS: For this study, 50 patients scheduled for laparoscopic cholecystectomy were randomized into five groups, then surgically treated with various pressures, light intensities, and dissection devices. Peritoneal biopsies were taken at the beginning and end of surgery. Tissue concentrations of total and active TGF-beta1 were measured using enzyme linked immunosorbent assay (ELISA) techniques. RESULTS: There was no significant difference in either total or active TGF-beta1 concentration between peritoneal biopsies taken at the start of surgery and samples taken at the end of the procedure. Patients who underwent surgery with the ultrasonic scalpel had significant lower levels of both active (p < 0.005) and total (p < 0.01) TGF beta1 at the end of surgery than patients treated with electrocautery. Patients who had surgery with a high light intensity had significantly lower levels of total TGF-beta1 levels (p < 0.005) with an unchanged active part than patients who had surgery with low light intensity. CONCLUSION: The choice of dissection device and the light intensity used in laparoscopic surgery affect peritoneal TGF beta1 concentrations, indicating that peritoneal biology can be affected by laparoscopic surgery. Because TGF-beta1 is involved in various biologic processes in the peritoneal cavity, this observation may have important clinical consequences. PMID- 17332966 TI - Laparoscopic-assisted peritoneal dialysis catheter placement: a microinvasive technique. AB - BACKGROUND: Peritoneal dialysis is an alternate form of dialysis for patients with end-stage renal disease (ESRD). Although not as widely used as hemodialysis, peritoneal dialysis (PD) has clear advantages, especially those related to patient satisfaction and simplicity. The purpose of our study was to describe and look at the results of a microinvasive technique for placement of peritoneal dialysis catheters under laparoscopy. METHODS: From August 2003 to January 2006, 12 patients with ESRD underwent laparoscopic-assisted peritoneal dialysis (LAPD) catheter placement with the microinvasive technique at our institution. Data collected included age, gender, underlying renal disease, and length of operation. Followup was completed for all patients (at least 6 months) and catheter-related morbidity and mortality were also analyzed. RESULTS: There were 13 procedures performed (one patient had LAPD catheter placement twice). The average age was 45 years and the most common cause of ESRD was uncontrolled arterial hypertension. Procedural time averaged 33.6 min (range = 24-50 min). Peritoneal dialysis was introduced two weeks after the procedure and no dialysate leaks were observed. There were two catheter-related morbidities; both were catheter exit-site abscesses, one managed surgically with removal of the PD catheter and the other managed conservatively with culture-sensitive antimicrobials. Patient satisfaction was beyond acceptable in 92% of the patients (12 of 13). Average longevity of the catheter was 61 weeks (427 days). There were no mortalities. CONCLUSION: LAPD catheter placement is an easy technique with acceptable catheter longevity and minimal morbidity. The microinvasive technique leads to better patient satisfaction and cosmetic outcome without affecting its function. Therefore, we believe that by promoting microinvasive LAPD catheter placement, PD will gain more acceptance among doctors and patients. PMID- 17332967 TI - Use of the urinary trypsinogen-2 dip stick test in early diagnosis of pancreatitis after endoscopic retrograde cholangiopancreatography. AB - BACKGROUND: This study aimed to prove that the urinary trypsinogen-2 dip stick test can be used for early diagnosis of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: For this prospective, blinded, pilot study, urine samples were collected before ERCP, 1 h after ERCP, and 4 h after ERCP. The urine dipstick test was used to detect trypsinogen-2 on the basis of immunochromatography. The dipstick results were compared with those of current methods used to diagnose post-ERCP pancreatitis. Once the patient disposition was finalized, pancreatic enzymes, clinical findings, and final diagnosis were obtained from the chart and compared with the urine trypsinogen-2 test findings. The sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: The urine trypsinogen dip stick test was performed for 30 patients (15 men and 15 women). Post-ERCP pancreatitis was diagnosed in 5 of 29 patients by clinician assessment, serum pancreatic enzyme levels, or both. The amylase and lipase levels for post-ERCP patients with and without pancreatitis were 650 +/- 145 vs 134 +/- 26 (p = 0.023) and 1,658 +/- 594 vs 84 +/- 17 (p = 0.057), respectively. This statement proves that patients who developed post ERCP pancreatitis had significant elevation of amylase and lipase compared to patients who did not have pancreatitis. For the dip stick test, 6 of 28 patients had positive results in 1 h and 6 of 29 patients had positive results in 4 h. The sensitivity of the 1-h test was 1.0, and the specificity was 0.91. The positive predictive value (PPV) was 0.66, and the negative predictive value (NPV) was 1.0. The sensitivity of the 4-h test was 1.0, and the specificity was 0.96. The PPV was 0.8, and NPV value was 1.0. CONCLUSION: The urinary trypsinogen-2 dip stick test is useful for early diagnosis of post-ERCP pancreatitis and allows the testing physicians to begin management early in its course. PMID- 17332968 TI - The involvement of arl-5b in the repair of hair cells in sea anemones. AB - The subcellular processes involved in repair of hair cells are not well understood. Sea anemones repair hair bundle mechanoreceptors on their tentacles after severe trauma caused by 1-h exposure to calcium-depleted seawater. Repair is dependent on the synthesis and secretion of large protein complexes named "repair proteins." A cDNA library on traumatized anemone tissue was probed using polyclonal antibodies raised to a specific chromatographic fraction of the repair protein mixture. An ADP-ribosylation factor-like protein, Arl-5b, was identified. The amino acid sequence of the Arl-5b protein in sea anemones is similar to that among several model vertebrates and humans. A polyclonal antibody raised to a peptide of the anemone Arl-5b labels some but not all hair bundles in healthy control animals. The abundance of labeled hair bundles significantly increases above healthy controls after trauma and continuing through the first hour of recovery. Dilute anti-Arl-5b blocks the spontaneous repair of hair bundle mechanoreceptors, suggesting that Arl-5b acts on the extracellular face of the plasma membrane. Immunoelectron microscopy indicates that Arl-5b is located along the length of stereocilia including sites in the vicinity of tip links. We propose that Arl-5b is involved in installing replacement linkages into damaged hair bundle mechanoreceptors. PMID- 17332970 TI - Hemoperitoneum following inguinal hernia repair: a case report. AB - Traditional inguinal herniorrhaphy continues to be one of the most common surgeries performed in the USA today. The procedure has developed into a straightforward, ambulatory procedure with postoperative complications being very rare. We describe the first report in the literature of the serious complication of hemoperitoneum after open inguinal hernia repair attributed to injury of the artery of Sampson. PMID- 17332969 TI - Effects of temporal fine structure on the lateralization of speech and on speech understanding in noise. AB - This study evaluated the role of temporal fine structure in the lateralization and understanding of speech in six normal-hearing listeners. Interaural time differences (ITDs) were introduced to invoke lateralization. Speech reception thresholds (SRTs) were evaluated in backgrounds of two-talker babble and speech shaped noise. Two-syllable words with ITDs of 0 and 700 micros were used as targets. A vocoder technique, which systematically randomized fine structure, was used to evaluate the effects of fine structure on these tasks. Randomization of temporal fine structure was found to significantly reduce the ability of normal hearing listeners to lateralize words, although for many listeners, good lateralization performance was achieved with as much as 80% fine-structure randomization. Most listeners demonstrated some rudimentary ability to lateralize with 100% fine-structure randomization. When ITDs were 0 micros, randomization of fine structure had a much greater effect on SRT in two-talker babble than in speech-shaped noise. Binaural advantages were also observed. In steady noise, the difference in SRT between words with 0- vs 700-micros ITDs was, on average, 6 dB with no fine-structure randomization and 2 dB with 100% fine-structure randomization. In two-talker babble this difference was 1.9 dB and, for most listeners, showed little effect of the degree of fine-structure randomization. These results suggest that (1) improved delivery of temporal fine structure would improve speech understanding in noise for implant recipients, (2) bilateral implant recipients might benefit from temporal envelope ITDs, and (3) improved delivery of temporal information could improve binaural benefits. PMID- 17332971 TI - Mycophenolate mofetil reduces disease activity and steroid dosage in Takayasu arteritis. AB - Mycophenolate mofetil (MMF) has recently been reported as a useful alternative immunosuppressive drug in autoimmune diseases including in Takayasu arteritis (TA). The aim of this study was to verify the efficacy and tolerability of MMF administration in controlling TA disease activity and allowing glucocorticosteroid reduction. Ten consecutive active TA patients followed at the Vasculitis Clinic were enrolled from January 2003 to 2006 and received oral MMF (2 g/day) for an average of 23.3 months. Disease activity assessed using the National Institutes of Health criteria, clinical features, and inflammatory laboratory findings were evaluated. Five patients had received at least one immunosuppressive drug before administration of MMF (four methotrexate, two azathioprine, and one chlorambucil) but had not achieved clinical and laboratory remission. The other five patients received MMF as their first immunosuppressive drug because of an important disease flare during steroid dose reduction. Clinical activity disappeared in all patients with MMF therapy, except in one patient who abandoned the study because of an important headache, attributed to the drug. Moreover, the MMF therapy allowed significant tapering of the prednisone dose in the rest of the nine patients (24.5 +/- 17.1 vs 5.8 +/- 7.8 mg/day; p = 0.0019). Reinforcing this finding, a significant reduction in inflammatory laboratory parameters, erythrocyte sedimentation rate (24.7 +/- 15.5 vs 12.8 +/- 10.8 mm/h; p = 0.036) and C-reactive protein (24.0 +/- 14.9 vs 11.2 +/- 10.7 mg/l; p = 0.0167), was observed. In summary, MMF therapy reduced clinical and laboratory parameters of TA disease activity, suggesting that this drug is a promising immunosuppressive drug, particularly in refractory cases and as a steroid-sparing agent. PMID- 17332972 TI - Combination of transverse myelitis and arachnoiditis in cauda equina syndrome of long-standing ankylosing spondylitis: MRI features and its role in clinical management. AB - The cauda equina syndrome (CES) is a rare neurological complication of ankylosing spondylitis (AS). Imaging diagnosis of CES in long-standing AS patients (CES-AS) using myelography, computed tomography (CT), and magnetic resonance imaging (MRI) were reported in the literature. They, however, demonstrate only the chronic abnormalities of CES-AS, i.e., dural ectasia, dorsal dural diverticula, and selective bone erosion at the posterior elements of the vertebrae. To our knowledge, imaging features of acute intradural inflammation in CES-AS were not described. We report a patient of CES-AS in whom MRI disclosed acute transverse myelitis and arachnoiditis along the lower spinal cord, and discuss the pathogenesis of CES-AS and the role of MRI in clinical management. PMID- 17332973 TI - Isoniazid intervention for latent tuberculosis among 86 patients with rheumatologic disease administered with anti-TNFalpha. AB - In this study, we investigated the safety and toxicity of isoniazid (INH) intervention therapy to the patients with latent tuberculosis who were given tumor necrosis factor alpha (TNFalpha) for the treatment of their rheumatologic diseases. In this prospective clinical study, we enrolled 86 patients receiving anti-TNFalpha therapy for their rheumatologic diseases between April 2005 and September 2006. Of all the subjects, 45 had rheumatoid arthritis, 36 had ankylosing spondylitis, and 5 had psoriatic arthritis. In addition to anti TNFalpha therapy, 60 of the 86 patients were given INH intervention for revealed latent tuberculosis. INH at a dosage of 300 mg daily was given for 9 months. Hepatotoxicity due to the INH therapy was considered when the serum alanine aminotransferase (ALT) and/or aspartate aminotransaminase (AST) levels showed at least threefold increase with respect to their baseline serum levels. Serum ALT and AST levels were measured by enzymatic colorimetric method in fasting peripheral blood samples at 0 (baseline), 1, 2, 3, 6, and 9 months. Of 86 patients, 47 (54.7%) were women (mean age+/-SD, 44.1 +/- 10.9 years) and 39 (45.3%) were men (38.8 +/- 10.1 years). Except five patients (8.3%), liver toxicity due to the INH therapy was not encountered among the patients, and after temporarily discontinuing the INH therapy of these five subjects, serum transaminase levels returned to the normal ranges. No hepatotoxicity was observed in the non-INH group. However, there was no statistical significance between INH treated and non-INH-treated group (p = 0.317). In addition, none of the 86 patients developed active tuberculosis infection during the treatment period. In conclusion, for those patients who were assigned to the TNFalpha treatment for their rheumatologic disorders and carrying risk for latent tuberculosis, INH intervention therapy was found to be safe and efficacious. PMID- 17332974 TI - No erosive progression revealed by MRI in rheumatoid arthritis patients treated with etanercept, even in patients with persistent MRI and clinical signs of joint inflammation. AB - The aim of this study is to investigate the course of magnetic resonance imaging (MRI) signs of inflammatory and destructive changes in rheumatoid arthritis (RA) wrist and metacarpophalangeal (MCP) joints during etanercept treatment. MRI of the non-dominant wrist and second to fifth MCP joints was performed in five clinical active RA patients before and 4 and 16 weeks after initiation of etanercept treatment. MRI was evaluated according to the EULAR-OMERACT RA MRI reference image atlas. The median 28-joint count disease activity score (DAS28; erythrocyte sedimentation rate based) was 5.6 (range 5.0-6.8) at baseline and 3.5 (1.5-4.1) at week 16 (decreased in all patients compared to baseline, Wilcoxon Pratt, p < 0.05). The median MRI synovitis score was 18 (14-21), 18 (10-20) and 16 (10-20) at baseline, week 4 and 16, respectively (decreased in all patients compared to baseline, Wilcoxon-Pratt, p < 0.05), while corresponding MRI bone oedema scores were 4 (0-13), 3 (0-9) and 1 (0-3; NS). The median MRI bone erosion score was 27 (11-111; NS) at all time points. Four patients had identical total bone erosion scores at baseline and week 16, whereas one patient showed a reduced score. In conclusion, one patient showed erosive regression, while no patient showed erosive progression on MRI during 16 weeks of etanercept therapy; even though clinical and MRI signs of joint inflammation remained. This small study supports that erosive progression judged by MRI is minimal in RA patients treated with etanercept, even in joints with persistent inflammation. PMID- 17332975 TI - Outcome of patients having dermatomyositis admitted to the intensive care unit. AB - Patients having systemic rheumatic diseases constitute a small percentage of admissions to the medical intensive care units (ICUs). Dermatomyositis (DM) is one of the rheumatic diseases that have secondary complications that may lead to a critical illness requiring hospitalization in the ICU. Herein, we present the features, clinical course, and outcome of critically ill patients having DM who were admitted to the ICU. The medical records of six DM patients admitted to the ICU in a large tertiary hospital in a 12-year period were reviewed. The mean age of patients at time of admission to the ICU was 38 (range 16-37). Mean disease duration from diagnosis to admission to the ICU was 1.6 years (range 1 month-8 years), while the main reason for admission to the ICU was acute respiratory failure. Two of six patients died during the hospitalization. The main causes of death were respiratory complications and sepsis. The outcome of DM patients admitted to the ICU was generally not different from the outcome of other patients hospitalized in the ICU. The main reason for hospitalization was acute respiratory failure. As there are many reasons for respiratory failure in DM, an early diagnosis and aggressive appropriate treatment may help to further reduce the mortality in these patients. PMID- 17332976 TI - Antiphospholipid antibodies in HIV-positive patients. AB - Antiphospholipid (aPL) antibodies classically have been associated with thrombotic phenomena and abortion in patients with autoimmune diseases. The objective of the present work was to evaluate the frequency of such antibodies in patients infected with HIV and study its association with the presence of clinical manifestations of antiphospholipid syndrome (APS). Using a transversal study, a population of patients diagnosed with HIV, identified through an enzyme linked immunosorbent assay (ELISA) test and confirmed by Western blotting, aged above 17 years old, was investigated. Through a standard questionnaire, the presence of APS manifestations was investigated, as well as the frequency of rheumatic manifestations. Antibodies against beta2 glycoprotein I (anti-beta2 GPI) and anticardiolipin (aCL) IgA, IgG, and IgM were investigated by the ELISA method using commercial kits (QUANTA Lite, INOVA Diagnostics). Ninety patients were studied, 47 (52.2%) male and 43 (47.8%) female. Clinical manifestations of APS were detected in 12 patients (13.3%) of the studied population, whereas arthralgia was the most common rheumatic manifestation (38.9%). Of the 90 patients, 40 (44.4%) were reactive for at least one type of aPL antibody (aCL and/or anti-beta2 GPI). The frequency of aCL was 17.8%, from which 15 (16.7%) had aCL IgG, 3 (3.3%) IgM, and 1 (1.1%) IgA. The frequency of the anti-beta2 GPI antibody was 33.3%, from which 29 (32.2%) were positive for isotype IgA, 4 (4.4%) isotype IgM, and 1 (1.1%) isotype IgG. No association was observed between immunoreactivity for aPL antibodies in general or each isotype in particular and the presence of APS manifestation. In the present study, it was possible to observe a relatively high frequency of aPL antibodies, particularly for isotype IgA anti-beta2 GPI in HIV. However, there was no association to APS manifestations, suggesting that such antibodies had no etiopathogenic role in these complications in patients with such retroviral infection. PMID- 17332978 TI - Clinical utility of magnetic resonance angiography (MRA) in the diagnosis and treatment of Takayasu's arteritis. PMID- 17332977 TI - Osteoarthritis of the knee and hip: a comparison of factors associated with physical activity. AB - To assess factors associated with physical activity (PA) in a large sample of primary care patients, 1,250 outpatients from 75 general practices were approached consecutively. Of these, 1,021 (81.7%) returned short forms of the international physical activity questionnaire (IPAQ) and the arthritis impact measurement scale (AIMS2-SF). In addition, the patient health questionnaire (PHQ 9) was used to assess concomitant depression. A stepwise multiple linear regression analysis with the IPAQ score as dependent variable was performed separately for knee and hip patients. The impact of osteoarthritis (OA) on patients with an affected knee (594/58.2%) was more severe, as reflected in higher scores in the "symptom", "lower body", and "affect" scales of the AIMS2-SF (p < 0.01 for all). These patients were also less active than patients with OA to the hip (p = 0.02 for IPAQ score). Main predictors of PA [change in p(F) for all factors < or =0.001] in knee OA patients were physical limitation to the lower limb (R(2) = 0.180), social network (R(2) = 0.121), pain (R(2) = 0.111), body mass index (R(2) = 0.041), and age (R(2) = 0.032). Predictors for OA at the hip (427/41.8%) differed slightly [change in p(F) for all factors < or =0.003): physical limitation to the lower limb (R(2) = 0.162), pain (R(2) = 0.131), PHQ-9 score (R(2) = 0.092), social network (R(2) = 0.078), and disease duration (R(2) = 0.043). Our findings suggest that factors associated with PA differ depending on the localization of the OA. Our results may help to tailor future interventions more appropriately. Further research is needed to determine whether these tailored interventions will result in increased PA. PMID- 17332979 TI - Anti-TNF therapy in the treatment of ankylosing spondylitis: the Finnish experience. AB - Biological therapy for ankylosing spondylitis (AS) has led to improved disease control beyond that of conventional treatments. International recommendations encourage clinicians prescribing biological treatments to register patients in national registers to collect information on outcome and toxicity. Patients with AS (n = 229) from the Register of Biological Treatment in Finland (ROB-FIN) with severe disease of long duration were followed-up for up to 24 months. Due to an active disease, one or more concomitant disease-modifying antirheumatic drugs (DMARDs) were used by 86% at commencement of biological therapy. This add-on strategy with infliximab led to a rapid pain relief and improvement of patient's and physician's global assessments, C-reactive protein/erythrocyte sedimentation rate, and swollen and tender joint counts within 6 weeks. Concomitant use of NSAID and oral corticosteroid was reduced. Corresponding results were documented at 3 months with etanercept, which was more recently approved for the treatment of spondyloarthropathies. Seventy-nine percent of the patients were ASAS 20 responders. A subgroup of AS patients with only axial involvement (n = 46) responded correspondingly. The first biological drug was discontinued in only 7% due to lack of efficacy and in 6% due to adverse events. Anti-TNF agents, often used in combination with DMARDs, appeared to have persistent effectiveness and limited toxicity in a real-life clinical setting in a cohort of Finnish AS patients with severe disease and long disease duration. PMID- 17332980 TI - Specificity and sensitivity of anti-beta2-glycoprotein I as compared with anticardiolipin antibody and lupus anticoagulant in Thai systemic lupus erythematosus patients with clinical features of antiphospholipid syndrome. AB - Antibodies to beta(2)-glycoprotein I (anti-beta(2)-GPI) have been reported to have stronger association with clinical antiphospholipid syndrome (APS) than anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). We investigated the sensitivity and specificity of ELISA for anti-beta(2)-GPI in Thai systemic lupus erythematosus (SLE) patients with clinical features of APS and compared the results with IgG/IgM aCL and LAC to find the test with the best association. The hospital records of 151 Thai SLE patients whose sera had been sent for either IgG/IgM anticardiolipin antibodies or lupus anticoagulant testing were reviewed. Sera of patients either without complete clinical records or those with APS related manifestations other than vascular thrombosis and pregnancy morbidity (according to the international consensus statement on preliminary classification criteria for definite APS) were excluded. For the remaining subjects (112 patients), their sera were tested for anti-beta(2)-GPI antibody, IgG and IgM anticardiolipin, and lupus anticoagulant. The sensitivity and specificity of each method were compared by using the chi-square test. Among the 112 (74.2%) SLE patients in the study, 35 (31.3%) presented with preliminary clinical criteria for APS (i.e., vascular thrombosis and pregnancy morbidity) whereas 77 (68.7%) did not. The sensitivity and specificity of anti-beta(2)-GPI determination were 57.1 and 79.2%, respectively, whereas those of IgG aCL were 25.7 and 94.8%, of IgM aCL were 5.7 and 98.7%, and of LAC were 44.8 and 77.3%, respectively. The accuracy of the four tests showed similar association with clinical APS (accuracy of test = 72.3, 73.2, 69.6, and 68.3%, respectively). Concerning the sensitivity, specificity, and difficulty of the methods, the combination of anti-beta(2)-GPI and IgG aCL tests was the best for the diagnosis of APS in Thai SLE patients. PMID- 17332981 TI - Nodular pulmonary amyloidosis in a patient with rheumatoid arthritis. AB - We describe a 67-year-old white woman with a long-standing active rheumatoid arthritis who refused treatment. Chest roentgenograms performed in 2000 revealed a pulmonary nodule in the mid-left lung. Progression of the nodule was followed annually by computerized tomography (CT). In the last CT in 2002, we observed multiple nodules in both lungs in the absence of lymph gland involvement. The patient was operated by video-thoracoscopy to resect one of the pulmonary nodules. Pathological examination of the excised tissue revealed amyloid A-type (AA) amyloidosis. Although pulmonary amyloidosis is rare in patients with systemic AA amyloidosis, we recommend that this possibility be considered when confronted with a patient with these characteristics. PMID- 17332982 TI - Depressive symptoms in early rheumatoid arthritis: a comparative longitudinal study. AB - Our objective was to investigate symptoms of depression in early rheumatoid arthritis (eRA) patients, and follow them longitudinally during a 3-year prospective study of 73 Hungarian and 45 Austrian early rheumatoid arthritis patients. Compared to validated national population data, mild symptoms of depression were detected in Hungarian early rheumatoid arthritis patients, which were independent of corticosteroid use. In the Hungarian subgroup, the Beck Depression Inventory scores were found to be stable during follow-up. Except at the baseline visit, depressive symptoms and functional status, as measured by the Health Assessment Questionnaire, were correlated. Significant differences were detected between Austrian and Hungarian patients despite of their geographical and cultural proximity. The mean depression score was higher in the Hungarian when compared to the Austrian patients. Depression is an important feature of early rheumatoid arthritis. Studies assessing depression in rheumatoid arthritis patients must be based on validated national data of normal population. PMID- 17332983 TI - Immunological diagnosis of cutaneous-pulmonary hypersensitivity vasculitis. AB - A 47-year-old woman had episodic dyspnoea, fatigue, chest radiograph opacifications, and palpable purpura whose biopsy showed leucocytoclastic vasculitis. Negative immunoglobulin A immunofluorescence staining and clinical exclusion of other disorders narrowed her diagnosis to cutaneous pulmonary hypersensitivity vasculitis. PMID- 17332984 TI - Associations of breast cancer development in patients with systemic sclerosis: an exploratory study. AB - The goal of this study was to describe the clinical characteristics of patients with a diagnosis of systemic sclerosis who develop breast cancer and to identify associations for this relationship. From 769 patients followed at the scleroderma center of our institution over the past 16 years, 24 patients developed a diagnosis of breast cancer. The demographics and clinical characteristics of these patients will be compared to those of a randomly selected group of scleroderma patients without a diagnosis of cancer. A further analysis will compare the patients who developed their breast cancer before the diagnosis of systemic sclerosis to those diagnosed after. Twenty-four patients developed 25 breast cancers with 13 patients diagnosed before the diagnosis of systemic sclerosis and 11 after. Compared to 48 randomly selected systemic sclerosis patients without a diagnosis of cancer, the patients with breast cancer were diagnosed with systemic sclerosis at an older age (53.5 +/- 15.2) as compared to those without (42.4 +/- 12.5) (p = 0.002). A relatively equal amount of patients had the diffuse and limited form of systemic sclerosis, while pulmonary fibrosis (p = 0.015) and the lack of antinuclear antibody (ANA) positivity (p = 0.02) were more commonly seen in patients with breast cancer. Patients who developed breast cancer before the diagnosis of systemic sclerosis were older at systemic sclerosis diagnosis (61.6 +/- 11.3) compared to those after (43.9 +/- 13.5) (p = 0.03). An older age at diagnosis of systemic sclerosis, a lack of ANA positivity, and the presence of pulmonary fibrosis were more commonly seen in patients with systemic sclerosis who have a diagnosis of breast cancer. PMID- 17332985 TI - A modified Hohmann method for hallux valgus and telescoping osteotomy for lesser toe deformities in patients with rheumatoid arthritis. AB - To preserve the function of metatarsophalangeal joints and to ensure forefoot stability in patients with rheumatoid arthritis (RA), we performed a modified Hohmann method for hallux valgus (HV) and telescoping osteotomy or shortening of lesser toe deformities. Forty-seven RA patients (90 feet) with severe HV and forefoot deformities were examined. The indication for the procedure in all the patients was disabling foot pain secondary to intractable plantar callosities below the lesser metatarsal heads and painful HV deformities. The HV and intermetatarsal (M1M2) angles and sesamoid complex were measured on the preoperative and postoperative roentgenograms. Visual analogue scales were studied preoperatively, postoperatively, and in the follow-up period. HV and M1M2 angles significantly improved compared between the pre- and postoperative conditions. Out of the 47 patients, 78.9% were satisfied with the results of the operation, 8.9% were unsatisfied, and 12.2% reported fair results. There were several complications, such as painful callosity, which was recurrent in seven feet, and delayed wound healing was observed in two out of the 90 feet. A modified Hohmann method and abductor hallucis muscle correction are effective in relieving pain and ensuring the bony union of the great toe in spite of severe osteoporosis. PMID- 17332986 TI - Tumefactive fibroinflammatory lesion of the lower extremity: a case report. AB - We report a case of tumefactive fibroinflammatory lesion located in the anterior, extracapsular part of the right knee, not responding to the conservative treatment. We discuss about the difficulty of the clinical diagnosis of this lesion. In the present case, only the histopathological characteristics confirmed the presence of fibroadipose and inflammatory tissue with lymphocytes and inflammatory cells. After 1 year from the surgical treatment, the patient was completely healed. PMID- 17332988 TI - Retinopathy of prematurity. AB - Retinopathy of prematurity (ROP) is a common blinding disease in children in the developed world despite current treatment, and is becoming increasingly prevalent in the developing world. ROP progresses in two phases. The first phase begins with delayed retinal vascular growth after birth and partial regression of existing vessels, followed by a second phase of hypoxia-induced pathological vessel growth. Two major risk factors of ROP are the use of oxygen and a decreased gestation period. Excessive oxygen contributes to ROP through regulation of vascular endothelial growth factor (VEGF). Suppression of VEGF by oxygen in phase I of ROP inhibits normal vessel growth, whereas elevated levels of VEGF induced by hypoxia in phase II of ROP precipitate pathological vessel proliferation. Insulin-like growth factor 1 (IGF-1) is a critical non-oxygen regulated factor in ROP. We have found that serum levels of IGF-1 in premature babies directly correlate with the severity of clinical ROP. IGF-1 acts indirectly as a permissive factor by allowing maximal VEGF stimulation of vessel growth. Lack of IGF-1 in preterm infants prevents normal retinal vascular growth in phase I of ROP, despite the presence of VEGF. As infants mature, rising levels of IGF-1 in phase II of ROP allows VEGF stimulated pathological neovascularization. These findings suggest that restoration of IGF-1 to normal levels might be useful in preventing ROP in preterm infants. PMID- 17332989 TI - Transcriptional responses of the deep-sea hyperthermophile Methanocaldococcus jannaschii under shifting extremes of temperature and pressure. AB - Growth and transcriptional profiles of the deep-sea methanarchaeon Methanocaldococcus jannaschii were studied under sudden up-shifts of temperature and pressure. Application of 500 atm of hyperbaric pressure shifted the optimal growth temperature upwards by about 5 degrees C in a high temperature-pressure bioreactor, and increased the specific growth rate threefold at 88 degrees C. In contrast, pressure-shock from 7.8 to 500 atm over 15 min, the first such pressure up-shift reported for a piezophile, did not accelerate growth. High-pressure heat shock from 88 to 98 degrees C, a condition relevant to the turbulent in situ surroundings of deep-sea hydrothermal vents, resulted in termination of growth. Transcriptional profiles for cells grown at 88 degrees C and 500 atm, heat shocked at 500 atm, and pressure-shocked to 500 atm, shared a subset of genes whose differential expression was attributed to elevated pressure. In the pressure-shock case, this transcriptional response was evident despite the absence of a piezophilic growth response. In all, despite the piezophilic capacity and high-pressure origins of M. jannaschii, the core pressure response was remarkably limited and consisted of differential expression of genes encoding three hypothetical proteins and a gene involved in DNA recombination. PMID- 17332990 TI - [Not Available]. PMID- 17332991 TI - [Not Available]. PMID- 17332992 TI - [Not Available]. PMID- 17332993 TI - [Not Available]. PMID- 17332994 TI - [Not Available]. PMID- 17332995 TI - [Not Available]. PMID- 17332996 TI - [Not Available]. PMID- 17332997 TI - [Not Available]. PMID- 17332998 TI - [Not Available]. PMID- 17332999 TI - [Not Available]. PMID- 17333002 TI - ACE inhibition in nutcracker syndrome with orthostatic proteinuria: how about a hemodynamic effect? PMID- 17333003 TI - Superior sagittal sinus thrombosis and bilateral sixth-nerve palsy in a child with nephrotic syndrome. AB - We report on a patient with nephrotic syndrome who developed superior sagittal sinus thrombosis. He presented with double vision due to bilateral sixth-nerve palsy and papilledema. The thrombosis resolved with intravenous heparin and oral corticosteroids. A month later there were no signs of ocular movement paresis, and both optic nerves were normal. PMID- 17333000 TI - Potassium transport in the maturing kidney. AB - The distal nephron and colon are the primary sites of regulation of potassium (K(+)) homeostasis, responsible for maintaining a zero balance in adults and net positive balance in growing infants and children. Distal nephron segments can either secrete or reabsorb K(+) depending on the metabolic needs of the organism. In the healthy adult kidney, K(+) secretion predominates over K(+) absorption. Baseline K(+) secretion occurs via the apical low-conductance secretory K(+) (SK) channel, whereas the maxi-K channel mediates flow-stimulated net urinary K(+) secretion. The K(+) retention characteristic of the neonatal kidney appears to be due not only to the absence of apical secretory K(+) channels in the distal nephron but also to a predominance of apical H-K-adenosine triphosphatase (ATPase), which presumably mediates K(+) absorption. Both luminal and peritubular factors regulate the balance between K(+) secretion and absorption. Perturbation in any of these factors can lead to K(+) imbalance. In turn, these factors may serve as effective targets for the treatment of both hyper-and hypokalemia. The purpose of this review is to present an overview of recent advances in our understanding of mechanisms of K(+) transport in the maturing kidney. PMID- 17333004 TI - Adolescent dialysis patient transition to adult care: a cross-sectional survey. AB - Adolescent dialysis patients transitioning to adult care are particularly vulnerable, dependent on complex, demanding and life-sustaining treatment. There is little published information on transition practices for this group. Therefore, a survey was carried out to assess the current status. Results are presented for 58 paediatric dialysis centres in North America and Europe. The majority of centres (53%) did not have a fixed cut-off age for transfer. For those that did, it ranged from 17 to 22 years, with the median 20.5 years and mean [+/- standard deviation (SD)] of 19.9 (+/-1.5) years. Only one third of centres reported a transition programme. Less than 20% of young adult patients were perceived to function autonomously at transfer. The paediatric centres had minimal knowledge of resources at the adult receiving sites. For the majority of programs there was a system in place to assist with application for social and health benefits (83%), an adult dialysis unit linked to the paediatric programme (62%) and an opportunity for patients to choose (78%) and visit (83%) the adult unit prior to transfer. Seventy-four percent of centres without a transition programme believed there was a need for one. This is an area clearly in need of attention. PMID- 17333005 TI - Adaptation of grasping responses to distorted object size and orientation. AB - The present study investigated the adaptive plasticity of the grasp component of prehensile movements. Subjects saw visual objects (V) of various sizes and orientations and were instructed to seize them with the thumb and index finger without manipulating them. The subjects' hand disappeared from view during the response and made contact with a haptic object (H), which could differ with respect to size or orientation from V. In Experiment A, we found that the grasp aperture adaptively increased when H > V and decreased when H < V. This confirms earlier observations and expands them by documenting that grasp size adaptation occurs even when grasping is not integrated into an intentional behavioral context (i.e., object manipulation). However, the magnitude of the observed adaptive size change was not monotonously related to the visual-haptic size difference, as one would expect for an adequate adaptive response. In Experiment B, we observed for the first time that the orientation of the grasp aperture adaptively changed when H was differently oriented than V. This change generalized to an unpracticed size and orientation of V, even in the absence of confirmative haptic feedback about dowel orientation. This outcome indicates that grasp orientation adaptation was at least partly based on the recalibration of sensory-to-motor transformation rules, rather than being completely due to strategic adjustments. PMID- 17333006 TI - Cognitive inhibition in patients with medial orbitofrontal damage. AB - Inhibition underlies cognitive processes such as overcoming habitual responses, suppressing of goal-irrelevant information, and switching of attention between stimuli or task rules. These processes are thought to depend on the frontal lobes. However, the precise role of the ventral frontal regions (orbitofrontal cortex) in these processes remains elusive. In the present study, our goal was to clarify the role of the orbitofrontal cortex in cognitive inhibition by examining the effects of focal lesions to the medial orbitofrontal cortex (posterior part of the gyrus rectus) on performance in tasks that required inhibitory control. Patients who had undergone surgery for an anterior communicating artery aneurysm and normal control subjects (C) participated in the study. The patients were subdivided into three groups: those with resection of the left (LGR+) or right (RGR+) gyrus rectus, and without such a resection (GR-). The Stroop Color-Word test, Trail Making B test, and the Category test were used as instruments for assessing response inhibition, switching between concrete stimuli, and switching between abstract task rules, respectively. In addition, the Digit Symbol test was used to examine sustained attention and processing speed. In the Stroop Color Word test, the RGR+ group performed worse than all other groups. In the Trail Making B test, the RGR+ and LGR+ groups performed worse than both the GR- and C groups. In the Category test and Digit Symbol test, the groups did not differ significantly from each other. Our study indicates a specific contribution of the medial orbitofrontal cortex to response inhibition and stimulus-based switching of attention. PMID- 17333007 TI - Alterations in presenilin 1 processing by amyloid-beta peptide in the rat retina. AB - Accumulating evidence indicates that mutations in the presenilin 1 (PS1) gene are responsible for most cases of familial Alzheimer's disease (AD). Although its biological functions are not yet fully understood, it appears that PS1 plays a role in the processing and trafficking of the amyloid precursor protein (APP). However, little is known about factors that are involved in regulating the metabolism of PS1 especially in relation to AD pathology. In this study, we have examined the effect of optic nerve crush, intravitreal injection of the inflammatory agent lipopolysaccharide (LPS) or injection of amyloid beta(1-42) (A beta(1-42)) on the expression and processing of PS1 in the rat retina. We found that 48 h after injection of A beta(1-42) there was a dramatic alteration in the banding pattern of PS1 on Western blots, as indicated by marked changes in the levels of expression of some of its C- and N-terminal fragments in retinal homogenates. These results suggest an A beta(1-42)-induced potentiation of a non specific stress-related but inflammation-independent alteration of processing of PS1 in this in vivo model. PMID- 17333008 TI - Elevated levels of brain-pathologies associated with neurodegenerative diseases in the methionine sulfoxide reductase A knockout mouse. AB - One of the posttranslational modifications to proteins is methionine oxidation, which is readily reversible by the methionine sulfoxide reductase (Msr) system. Thus, accumulation of faulty proteins due to a compromised Msr system may lead to the development of aging-associated diseases like neurodegenerative diseases. In particular, it was interesting to monitor the consequential effects of methionine oxidation in relation to markers that are associated with Alzheimer's disease as methionine oxidation was implied to play a role in beta-amyloid toxicity. In this study, a knockout mouse strain of the methionine sulfoxide reductase A gene (MsrA ( -/- )) caused an enhanced neurodegeneration in brain hippocampus relative to its wild-type control mouse brain. Additionally, a loss of astrocytes integrity, elevated levels of beta-amyloid deposition, and tau phosphorylation were dominant in various regions of the MsrA ( -/- ) hippocampus but not in the wild-type. Also, a comparison between cultured brain slices of the hippocampal region of both mouse strains showed more sensitivity of the MsrA ( -/- ) cultured cells to H(2)O(2) treatment. It is suggested that a deficiency in MsrA activity fosters oxidative-stress that is manifested by the accumulation of faulty proteins (via methionine oxidation), deposition of aggregated proteins, and premature brain cell death. PMID- 17333009 TI - Perceptual learning: how much daily training is enough? AB - The acquisition of many perceptual skills proceeds over a course of days. However, little is known about how much daily training is needed for such learning to occur. Here we investigated this question by examining how varying the number of training trials per day affected learning over multiple days on two auditory discrimination tasks: frequency discrimination and temporal-interval discrimination. For each task, we compared improvements in discrimination thresholds between different groups of listeners who were trained for either 360 or 900 trials per day for 6 days. Improvement on frequency discrimination required >360 trials of training per day while learning on temporal-interval discrimination occurred with 360 training trials per day, and additional daily practice did not increase the amount of improvement. It therefore appears that the accumulation of improvement over days on auditory discrimination tasks may require some critical amount of training per day, that training beyond that critical amount yields no additional learning on the trained condition, and that the critical amount of training needed varies across tasks. These results imply that perceptual skills are transferred from short- to long-term memory (consolidated) daily, but only if a task-specific initiation requirement has been met. PMID- 17333010 TI - Multi-sensory integration of spatio-temporal segmentation cues: one plus one does not always equal two. AB - How are multiple, multi-sensory stimuli combined for use in segmenting spatio temporal events? For an answer, we measured the effect of various auditory or visual stimuli, in isolation or in combination, on a bistable percept of visual motion ("bouncing" vs. "streaming"). To minimize individual differences, the physical properties of stimuli were adjusted to reflect individual subjects' sensitivity to each cue in isolation. When put into combination, perceptual influences that had been equipotent in isolation were substantially altered. Specifically, auditory cues that had been strong when presented alone were greatly reduced in combination. Evaluation of alternative models of sensory integration showed that the state of the visual bistable percept could not be accounted for by probability summation among cues, as might occur at the level of decision processes. Instead, the state of the bistable percept was well predicted from a weighted sum of cues, with visual cues strongly dominating auditory cues. Finally, when cue weights were compared for individual subjects, it was found that subjects differ somewhat in the strategy they use for integrating multi sensory information. PMID- 17333012 TI - Seeing the light: exploring the Colavita visual dominance effect. AB - The Colavita visual dominance effect refers to the phenomenon whereby participants presented with unimodal auditory, unimodal visual, or bimodal audiovisual stimuli in a speeded discrimination task, fail to respond to the auditory component of bimodal targets significantly more often than they fail to respond to the visual component. The Colavita effect was demonstrated in this study when participants were presented with unimodal auditory, unimodal visual, or bimodal stimuli (in the ratios 40:40:20, Experiment 1; or 33:33:33, Experiment 2), to which they had to respond by pressing an auditory response key, a visual response key, or both response keys. The Colavita effect was also demonstrated when participants had to respond to the bimodal targets using a dedicated third (bimodal) response key (Experiment 3). These results therefore suggest that stimulus probability and the response demands of the task do not contribute significantly to the Colavita effect. In Experiment 4, we investigated what role exogenous attention toward a sensory modality plays in the Colavita effect. A significantly larger Colavita effect was observed when a visual cue preceded the bimodal target than when an auditory cue preceded it. This result suggests that the Colavita visual dominance effect can be partially explained in terms of the greater exogenous attention-capturing qualities of visual versus auditory stimuli. PMID- 17333011 TI - Consolidation of object-discrimination memory is independent of the hippocampus in rats. AB - We examined whether retrograde amnesia would be more likely for object discriminations learned an hour before hippocampal damage than object discriminations learned days before. Specifically, rats were trained on two object-discrimination problems 72 h before surgery and another discrimination problem and the reversal of one of the previously learned problems 1 h before surgery. Importantly, novel procedures that minimized overtraining on the object discriminations were used to increase the possibility of the lesions causing amnesia. After either receiving sham or neurotoxic-induced hippocampal damage, rats were tested for retention using an extinction procedure. Control rats and rats with extensive hippocampal damage displayed a strong bias for the rewarded object on each object-discrimination problem and a significant bias for the most recent contingency learned on the reversal problem. These results suggest that, despite the use of very sensitive training and testing procedures, hippocampal damage did not cause retrograde amnesia. The findings imply that the hippocampus is not critical for the consolidation, storage, or retrieval of object-reward associations, or any other information required for accurate performance of an object discrimination. PMID- 17333013 TI - Neural noise distorts perceived motion: the special case of the freezing illusion and the Pavard and Berthoz effect. AB - When a slowly moving pattern is presented on a monitor which itself is moved, the pattern appears to freeze on the screen (Mesland and Wertheim in Vis Res 36(20):3325-3328, 1996) even if we move our head with the monitor, as with a head mounted display (Pavard and Berthoz in Perception 6:529-540, 1977). We present a simple model of these phenomena, which states that the perceived relative velocity between two stimuli (the pattern and the moving monitor) is proportional to the difference between the perceived velocities of these stimuli in space, minus a noise factor. The latter reflects the intrinsic noise in the neural signals that encode retinal image velocities. With noise levels derived from the literature the model fits empirical data well and also predicts strong distortions of visually perceived motion during vestibular stimulation, thus explaining both illusions as resulting from the same mechanism. PMID- 17333014 TI - Characterization of directly transformed weedy Brassica rapa and introgressed B. rapa with Bt cry1Ac and gfp genes. AB - Crop to weed transgene flow, which could result in more competitive weed populations, is an agricultural biosafety concern. Crop Brassica napus to weedy Brassica rapa hybridization has been extensively characterized to better understand the transgene flow and its consequences. In this study, weedy accessions of B. rapa were transformed with Bacillus thuringiensis (Bt) cry1Ac- and green fluorescence protein (gfp)-coding transgenes using Agrobacterium to assess ecological performance of the wild biotype relative to introgressed hybrids in which the transgenic parent was the crop. Regenerated transgenic B. rapa events were characterized by progeny analysis, Bt protein enzyme-linked immunosorbent assay (ELISA), Southern blot analysis, and GFP expression assay. GFP expression level and Bt protein concentration were significantly different between independent transgenic B. rapa events. Similar reproductive productivity was observed in comparison between transgenic B. rapa events and B. rapa x B. napus introgressed hybrids in greenhouse and field experiments. In the greenhouse, Bt transgenic plants experienced significantly less herbivory damage from the diamondback moth (Plutella xylostella). No differences were found in the field experiment under ambient, low, herbivore pressure. Directly transformed transgenic B. rapa plants should be a helpful experimental control to better understand crop genetic load in introgressed transgenic weeds. PMID- 17333015 TI - Proteome analysis of embryogenic cell suspensions of cowpea (Vigna unguiculata). AB - Using a combination of two-dimensional gel electrophoresis protein mapping and mass spectrometry analysis, we have established proteome reference maps of embryogenic cell suspensions of cowpea (Vigna unguiculata). The cell suspensions were generated from young primary leaves and contained basically pro-embryogenic masses, which enabled us to dissect their proteome composition while eliminating the complexity of too many cell types. Over 550 proteins could reproducibly be resolved over a pI range of 3-10. A total of 128 of the most abundant protein spots were excised, digested in-gel with trypsin and analyzed by tandem mass spectrometry. This enabled the identification of 67 protein spots. Two of the most abundant proteins were identified as a chitinase and as a ribonuclease belonging to the family of PR-4 and PR-10 proteins, respectively. The expression of the respective genes was confirmed by RT-PCR and the pattern of deposition of the PR-10 protein in cell suspensions as well as in developing cowpea seeds, roots, shoots and flowers were determined by Western blot experiments, using synthetic antibodies raised against a 14-amino acid synthetic peptide located close to the C-terminal region of the PR-10 protein. PMID- 17333016 TI - Genetic instability in calamondin (Citrus madurensis Lour.) plants derived from somatic embryogenesis induced by diphenylurea derivatives. AB - Somatic embryos were regenerated in vitro from calamondin style-stigma explants cultured in the presence of N (6)-benzylaminopurine (BAP) cytokinin and three synthetic phenylurea derivatives, N-(2-chloro-4-pyridyl)-N-phenylurea (4-CPPU), N phenyl-N'-benzothiazol-6-ylurea (PBU) and N,N'-bis-(2,3-methilendioxyphenyl)urea (2,3-MDPU). The phenylurea derivative compounds tested at micromolar level (12 muM) were able to induce a percentage of responsive explants significantly higher from that obtained with BAP and hormone-free (HF) conditions. In order to verify the genetic stability of the regenerants, 27 plants coming from different embryogenic events were randomly selected from each different culture condition and evaluated for somaclonal variations using inter-simple sequence repeat and random amplified polymorphic DNA analyses. We observed that 2,3-MDPU and PBU gave 3.7% of somaclonal mutants, whereas 4-CPPU gave 7.4% of mutants. No somaclonal variability was observed when plantlets were regenerated in BAP or HF medium. Although diphenylurea derivatives show a higher embryogenic potential as compared to BAP, they induce higher levels of somaclonal variability. This finding should be taken in consideration when new protocols for clonal propagation are being developed. PMID- 17333017 TI - Cloning of a 9-cis-epoxycarotenoid dioxygenase gene (SgNCED1) from Stylosanthes guianensis and its expression in response to abiotic stresses. AB - Abscisic acid (ABA) regulates plant adaptive responses to various environmental stresses. Oxidative cleavage of cis-epoxycarotenoids catalyzed by 9-cis epoxycarotenoid dioxygenase (NCED) is the main regulatory step in the biosynthesis of ABA in higher plants. A NCED gene, SgNCED1, was cloned from the dehydrated leaves of Stylosanthes guianensis. The 2,241-bp full-length SgNCED1 had a 1,809-bp ORF, which encodes a peptide of 602 amino acids. The deduced amino acid sequence of SgNCED1 protein shared high identity with other NCEDs. At the N terminus of the SgNCED1 located a chloroplast transit peptide sequence. DNA blot analysis revealed that SgNCED1 was a single copy gene in the genome of S. guianensis. The relationship between expression of SgNCED1 and endogenous ABA level was investigated. The expression of SgNCED1 was induced in both leaves and roots of S. guianensis under drought stress. Dehydration and salt stress induced the expression of SgNCED1 strongly and rapidly. The ABA accumulation was coincidently induced with the SgNCED1 mRNA under drought, dehydration and salt stress. The expression of SgNCED1 and ABA accumulation were also induced under chilling condition. PMID- 17333018 TI - Stable transformation and long-term maintenance of transgenic Taxus cell suspension cultures. AB - A cell line of Taxus cuspidata has been transformed with wild-type Agrobacterium rhizogenes ATCC strain 15834 containing binary vector pCAMBIA1301 and, separately, with A. tumefaciens strain EHA105 containing binary vector pCAMBIA1305.2. Additionally, a cell line of T. chinensis has been transformed with wild-type A. rhizogenes ATCC strain 25818 containing binary vector pCAMBIA1301. The two transgenic T. cuspidata cell lines have been maintained in culture for more than 20 months, and the transgenic T. chinensis cell line for more than 9 months, with no loss of reporter gene expression or antibiotic resistance. The introduced genes had no discernable effect on growth or Taxol production in the transgenic cell lines when compared to the parent control. The methods for transforming non-embryogenic Taxus suspension cultures are described. PMID- 17333019 TI - Chloroplast targeting of FanC, the major antigenic subunit of Escherichia coli K99 fimbriae, in transgenic soybean. AB - Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of enteric diseases affecting livestock and humans. Edible transgenic plants producing E. coli fimbrial subunit proteins have the potential to vaccinate against these diseases, but have not reached their full potential as a renewable source of oral vaccines due in part to insufficient levels of recombinant protein accumulation. Previously, we reported that cytosol targeting of the E. coli K99 fimbrial subunit antigen resulted in FanC accumulation to approximately 0.4% of total soluble protein in soybean leaves (Piller et al. in Planta 222:6-18, 2005). In this study, we report on the subcellular targeting of FanC to chloroplasts. Twenty-two transgenic T1 progeny derived from seven individual T0 transformation events were characterized, and 17 accumulated transgenic FanC. All of the characterized events displayed relatively low T-DNA complexity, and all exhibited proper targeting of FanC to the chloroplast. Accumulation of chloroplast-targeted FanC was approximately 0.08% of total soluble leaf protein, or approximately 5 fold less than cytosol-targeted FanC. Protein analysis of leaves at various stages of maturity suggested stability of chloroplast-targeted FanC throughout leaf maturation. Furthermore, mice immunized intraperitoneally with protein extract derived from transgenic leaves expressing chloroplast-targeted FanC developed significant antibody titers against FanC. This is the first report of subcellular targeting of a vaccine subunit antigen in soybean. PMID- 17333020 TI - Non-antibiotic, efficient selection for alfalfa genetic engineering. AB - A selectable marker gene (SMG), usually conferring resistance to an antibiotic or herbicide, is generally introduced into the plant cells with the gene(s) for the trait of interest to allow only the cells that have integrated and express the foreign sequences to regenerate into a plant. The availability of several SMGs for each plant species is useful for both basic and applied research to combine several genes of interest in the same plant. A selection system based on gabaculine (3-amino-2,3-dihydrobenzoic acid) as the selective substance and the bacterial hemL gene [encoding a mutant for of the enzyme glutamate 1-semialdehyde aminotransferase (GSA-AT)] as the SMG was previously used for genetic transformation of tobacco. The hemL gene is a good candidate for a safe SMG, because GSA-AT is present in all plants and is likely involved in one metabolic step only, so that unintended effects of its overexpression in plants are not probable. In this work, we have compared this new selection system with the conventional, kanamycin-based system for alfalfa Agrobacterium-mediated transformation. The hemL and NptII genes were placed together into a T-DNA under the control of identical promoters and terminators. We show that the gabaculine based system is more efficient than the conventional, kanamycin-based system. The inheritance of hemL was Mendelian, and no obvious phenotypic effect of its expression was observed. PMID- 17333021 TI - Auxin pulse treatment holds the potential to enhance efficiency and practicability of somatic embryogenesis in potato. AB - The objective of the current study was to simplify existing somatic embryogenesis systems in potato (Solanum tuberosum L.) cv. Desiree. The project targeted the agar-based induction phase of the potato somatic embryogenesis process as the key area for improvement. Experiments were established to ascertain the effect of a 2,4-D (2,4 dichlorophenoxyacetic acid) pulse, applied to the primary internodal section explant source and its subsequent effect on embryo induction. Parameters tested were the duration of the auxin pulse in a range from 0 to 300 min, and the concentrations of 2,4-D applied, in a range from 0 to 5,120 microM. The mean number of somatic embryos formed per explant was recorded after 4 and 8 weeks culture. Our findings indicated that the somatic embryogenesis in potato internodal segments could be evoked by an auxin (2,4-D) pulse treatment over a wide concentration and duration range. The results further suggested that a simple 20 microM 2,4-D pulse treatment could replace a lengthy 2 week induction phase in potato somatic embryogenesis and thus improve the system's practicability for wider uptake. PMID- 17333022 TI - Molecular cloning and overexpression of a novel UDP-glucosyltransferase elevating salidroside levels in Rhodiola sachalinensis. AB - Salidroside is a novel effective adaptogenic drug extracted from the medicinal plant Rhodiola sachalinensis A. Bor. Because this plant is a rare resource and has low yield, there is great interest in enhancing the production of salidroside. In this study, a putative UDP-glucosyltransferase (UGT) cDNA, UGT73B6, was isolated from Rhodiola sachalinensis using a rapid amplification of cDNA ends (RACE) method. The cDNA was 1,598 bp in length encoding 480 deduced amino acid residues with a conserved UDP-glucose-binding domain (PSPG box). Southern blot analysis of genomic DNA indicated that UGT73B6 existed as a single copy gene in the R. sachalinensis genome. Northern blot analysis revealed that transcripts of UGT73B6 were present in roots, calli and stems, but not in leaves. The UGT73B6 under 35S promoter with double-enhancer sequences from CaMV-Omega and TMV-Omega fragments was transferred into R. sachalinensis via Agrobacterium tumefaciens. PCR, PCR-Southern and Southern blot analyses confirmed that the UGT73B6 gene had been integrated into the genome of transgenic calli and plants. Northern blot analysis revealed that the UGT73B6 gene had been expressed at the transcriptional level. High performance liquid chromatography (HPLC) analysis indicated that the overexpression of the UGT73B6 gene resulted in an evident increase of salidroside content. These data suggest that the cloned UGT73B6 can regulate the conversion of tyrosol aglycon to salidroside in R. sachalinensis. This is the first cloned glucosyltransferase gene involved in salidroside biosynthesis. PMID- 17333023 TI - Expression of MdCAS1 and MdCAS2, encoding apple beta-cyanoalanine synthase homologs, is concomitantly induced during ripening and implicates MdCASs in the possible role of the cyanide detoxification in Fuji apple (Malus domestica Borkh.) fruits. AB - Fruit ripening involves complex biochemical and physiological changes. Ethylene is an essential hormone for the ripening of climacteric fruits. In the process of ethylene biosynthesis, cyanide (HCN), an extremely toxic compound, is produced as a co-product. Thus, most cyanide produced during fruit ripening should be detoxified rapidly by fruit cells. In higher plants, the key enzyme involved in the detoxification of HCN is beta-cyanoalanine synthase (beta-CAS). As little is known about the molecular function of beta-CAS genes in climacteric fruits, we identified two homologous genes, MdCAS1 and MdCAS2, encoding Fuji apple beta-CAS homologs. The structural features of the predicted polypeptides as well as an in vitro enzyme activity assay with bacterially expressed recombinant proteins indicated that MdCAS1 and MdCAS2 may indeed function as beta-CAS isozymes in apple fruits. RNA gel-blot studies revealed that both MdCAS1 and MdCAS2 mRNAs were coordinately induced during the ripening process of apple fruits in an expression pattern comparable with that of ACC oxidase and ethylene production. The MdCAS genes were also activated effectively by exogenous ethylene treatment and mechanical wounding. Thus, it seems like that, in ripening apple fruits, expression of MdCAS1 and MdCAS2 genes is intimately correlated with a climacteric ethylene production and ACC oxidase activity. In addition, beta-CAS enzyme activity was also enhanced as the fruit ripened, although this increase was not as dramatic as the mRNA induction pattern. Overall, these results suggest that MdCAS may play a role in cyanide detoxification in ripening apple fruits. PMID- 17333024 TI - Transcript profiling of terpenoid indole alkaloid pathway genes and regulators reveals strong expression of repressors in Catharanthus roseus cell cultures. AB - The understanding of the complexities and molecular events regulating genes and the activators involved in terpenoid indole alkaloid (TIA) metabolism is known to a certain extent in cell cultures of an important TIA yielding plant, Catharanthus roseus, though it is not yet complete. Recently, the repressors of early TIA pathway genes have also been identified. However, their roles in the regulation of TIA pathway in C. roseus cell cultures remains yet unknown. We have made a comparative profiling of genes catalyzing the important steps of 2-C methyl-D-erythritol-4-phosphate (MEP), shikimate and TIA biosynthetic pathways, their activator and repressors using macroarray, semiquantitative RT-PCR and northern analyses in a rotation culture system of C. roseus comprising differentiated and proliferated cells. Our results demonstrate that TIA biosynthetic pathway genes and their activators show variable expression pattern, which was correlated with the changes in the cellular conditions in these systems. Under similar conditions, TIA pathway repressors show strong and consistent expression. The role of repressors in the complex regulation of the TIA pathway in C. roseus cell cultures is discussed. The results were supported by HPLC data, which demonstrated that the molecular program of cellular differentiation is intimately linked with TIA pathway gene expression and TIA production in C. roseus cell cultures. PMID- 17333025 TI - [Mycosis fungoides: complications of long term treatment with PUVA and ECP]. PMID- 17333026 TI - [Combination treatment of a cutaneous non-Hodgkin's lymphoma with rituximab and polychemotherapy]. PMID- 17333027 TI - [Multiple eruptive dermatofibroma]. PMID- 17333028 TI - [Disseminated erythema nodosum]. PMID- 17333029 TI - [Bullous pemphigoid: first manifestation under a picture of prurigo simplex subacuta]. PMID- 17333030 TI - [Rowell syndrome]. PMID- 17333031 TI - Immunolocalization and mRNA expression of the epithelial Na+ channel alpha subunit in the kidney and urinary bladder of the marine toad, Bufo marinus, under hyperosmotic conditions. AB - The amiloride-sensitive epithelial sodium channel (ENaC) has previously been shown to be involved in the maintenance of body fluid volume and in Na(+) absorption across the skin and urinary bladder in amphibians. However, the function and distribution of ENaC have not been clearly described in amphibian kidney. We therefore cloned the ENaC alpha-subunit cDNA from kidney of the marine toad, Bufo marinus. The ENaC mRNA and protein were abundantly expressed in the kidney and in the urinary bladder and ventral pelvic skin. In an immunohistochemical study, the ENaC alpha-subunit protein was specifically localized to the apical membrane of the principal cells but not the intercalated cells from the late distal tubule to the collecting duct in the kidney or in the apical area of cells of urinary bladder epithelia. When toads were acclimated to dry and hyper-saline environments, the levels of ENaC mRNA expression in the kidney and urinary bladder decreased under hyper-saline acclimation, but not under dry conditions. Immunohistochemical observations indicated that the levels of ENaC protein expression were much lower in the apical area of renal distal tubules and urinary bladder epithelia of hyper-saline acclimated toad compared with controls. The present study suggests that Bufo ENaC is significantly expressed and functions during Na(+) reabsorption in the apical membrane domain in the distal nephron of normal and desiccated toads. Natriuresis may be caused by decreases in ENaC expression and its trafficking to the cell surface in the distal nephron, a response to prevent excessive Na(+) reabsorption in hyper saline-acclimated toads. PMID- 17333032 TI - Morphofunctional changes in Leydig cells throughout the continuous spermatogenesis of the freshwater teleost fish, Serrasalmus spilopleura (Characiformes, Characidae): an ultrastructural and enzyme study. AB - The freshwater fish Serrasalmus spilopleura (piranha) has a continuous type of reproduction; gametes are constantly produced and released during the reproductive cycle. The testes do not undergo seasonal morphological changes but exhibit two constant regions throughout the year: the medullar region (involved with spermatogenesis) and the cortical region (involved with spermiation and sperm storage). We have evaluated the ultrastructure of the Leydig cells and the activity of 3beta-HSD (an essential enzyme related to steroid hormone biosynthesis) and acid phosphatase (AcPase; lysosomal marker enzyme) in these two regions. The activity of 3beta-HSD is stronger in the medullar region, and the Leydig cells in this region have a variety of cytological features that reflect differences in hormone synthesis and/or that could be linked to steroidogenic cells under various degrees of hormonal activity. In the cortical region, 3beta HSD activity is weak and the Leydig cells exhibit signs of degeneration, as confirmed by their ultrastructure and intense AcPase activity. These degenerative signs are indicative of cytoplasmic remodelling to degrade steroidogenic enzymes, such as 3beta-HSD, that could lead to senescence or even to autophagic cell degeneration. S. spilopleura thus constitutes an interesting model for increasing our understanding of steroidogenesis control in freshwater teleost fish. PMID- 17333033 TI - [How do I write an original article? An introduction for beginners]. AB - Less than 50% of abstracts presented on scientific conferences get published as full articles. This manuscript is a hands-on instruction on how to collate a scientific investigation into an article. Criteria for authorship should be decided based on the Vancouver statement. The first step is a description of materials and methods including the statistical analysis (approximately 1,000 words), which should already be done during the study itself. The second step is describing the results without interpretation (approximately 350 words); graphs are better than tables. The discussion (approximately 1,000-1,350 words) is initiated with a short description of the most important results, followed by a defence of the model employed. Subsequently, the mechanisms of the results are discussed and put into context with the results of comparable studies; the clinical implication of the most important aspects should be discussed. This is followed by the limitations of the investigation to allow a realistic classification; the conclusions should be low-key rather than exaggerated. The last step is the introduction (approximately 350 words), which has to "hit the nail on the head" in order to attract the reader; this is followed by the abstract and references. Issues that are absolutely to be avoided are insufficient preparation of the study, no answers to the hypothesis of the study, contradictions within the manuscript, superficial discussion, changing terms, reflexive sentences, and a conclusion that is not supported by the data. The first author and mentor should write the first draft of the manuscript; subsequently, the co-authors have to contribute with constructive critique to improve the article until a final draft has been achieved after several rounds of revision and further critique. A journal should be targeted where the manuscript has a realistic chance of publication. If the reviewer's comments can be answered, a careful revision is always warranted and should be performed even if the editor rejected the manuscript. All parties involved should be informed about each step of the project by the first author in order to ensure enduring success. PMID- 17333034 TI - [Pulmonary artery catheter in anaesthesia and intensive care medicine]. PMID- 17333035 TI - [Key performance indicators of OR efficiency. Myths and evidence of key performance indicators in OR management]. AB - A variety of different key performance indicators, both for process and financial performance, are used to evaluate OR efficiency. Certain indicators like OR utilization and turnover times seem to become common standard in many hospitals to evaluate OR process performance. Despite the general use and availability of these indicators in OR management, the scientific evidence behind these data is relatively low. These process indicators are strongly influenced by artefacts and depend on planning process, resource allocation and documentation. Direct financial indicators become more important with increasing autonomy of OR management. Besides budgetary compliance the focus is set on the net results of internal transfer pricing systems. By taking part in an internal transfer pricing system, OR management develops from a mere passive cost center to an active shaper of perioperative processes. However, detailed knowledge of the origin of costs and pitfalls of internal transfer pricing systems is crucial. The increased transparency due to the free accessibility of diagnosis-related-groups (DRG) cost breakdown data can help to develop tools for economic analysis of OR efficiency. PMID- 17333037 TI - [Lymphadenectomy with tumors of the upper gastrointestinal tract]. AB - In surgical therapy for upper gastrointestinal cancer, adequate lymphadenectomy together with R0 resection of the primary tumour is one of the most important prognostic factors which can be influenced by the surgeon. Recommendations for localization- and stage-adapted lymphadenectomy can be made according to histopathologic and anatomic investigations of the patient collectives of large centres. After neoadjuvant radiochemotherapy in cancer of the cervical oesophagus, the absence of lymph nodes on the resected specimen seems to be of less prognostic value. In squamous cell cancer of the suprabifurcal oesophagus, radical lymphadenectomy is recommended. Despite significant morbidity, in specialized centres this procedure yields good results with low mortality. For infrabifurcal oesophageal cancer, two-field lymphadenectomy during the so-called Ivor-Lewis operation is the method of choice. Locally advanced Barrett carcinoma is also an indication for classic two-field lymphadenectomy together with abdominothoracic oesophagectomy and creation of a stomach tube with intrathoracic anastomosis. The lymphadenectomy should however include the area of retroperitoneal lymphatic drainage at the pedicle of the left kidney. Submucosal cancer in this area can be treated with luminal limited resection of the oesophagogastric junction with adequate lymphadenectomy. Adenocarcinoma of the cardia and subcardial gastric cancer including the cardia both require lymphadenectomy analogous to that performed in gastric cancer, with special attention paid to the retroperitoneal lymphatic drainage towards the left kidney pedicle. For therapy of gastric cancer, a systematic D2 lymphadenectomy should always be performed. PMID- 17333036 TI - [Lymphadenectomy with tumors of the lower gastrointestinal tract]. AB - For advanced adenocarcinomas, which are the most frequent tumours of the lower GI tract, the concept of radical lymphnode dissection is well accepted. The quality of lymphadenectomy for these malignancies has a strong effect on cancer-related survival. Based upon a strict quality control program with outcome evaluated according to internal results, the technique and extent of lymph node dissection have been continuously developed over the last three decades. These are described in detail, including instructive pictures to clarify the surgical steps needed. Apart from multivisceral resection in far advanced cases, which still have a chance of cure if adequate guidelines are followed, two additional steps in the so-called radical surgical treatment of these tumours are prerequisites for cure. The first is complete mobilisation of the intestine involving complete mesocolic excision with complete retention of the visceral fascia and covering potential lymph node metastases and extranodal spread on the intestinal side. The second step is the central tying of the tumor's supplying vessels. Following these rules and with no adjuvant systemic treatment, 5-year survival figures of 80% can be reached, even for UICC stage III disease. PMID- 17333038 TI - [Body contouring surgery after massive weight loss. Part I: abdomen and extremities]. AB - Body contouring surgery is traditionally part of plastic surgery training. Reconstructive techniques are needed most in trauma cases, tumor reconstructions, treatment of degenerative diseases and metabolic diseases such as Madelung's deformity, body contouring after massive weight loss, and all aesthetic plastic surgery. With various surgical techniques, liposuction became an important option in the overall treatment plan. Body contouring surgery in the massive weight loss patient is a rapidly expanding field of plastic surgery. Its challenge is the management of excess skin remaining after bariatric surgery. To achieve an aesthetic body contour, patients must accept numerous long scars. They must understand that recurrent laxity and scar migration is not necessarily a failure of the operation but rather an expected outcome. Body contouring surgery is challenging, time-consuming, and not without complications. The patient population has very real aesthetic and appearance concerns that must be addressed in an effective, definite, and safe manner. PMID- 17333040 TI - [Significance of the medical history in decisions on whether tonsillotomy is indicated]. AB - BACKGROUND: In pre-school children suffering from pure non-inflammatory hyperplasia of the tonsils, tonsillotomy has recently been recommended in preference to tonsillectomy. Absence of inflammatory tonsillitis in the previous medical history is accepted as evidence that tonsillotomy is indicated. In this study, we therefore examine whether and to what degree the medical history correlates with the histological findings. PATIENTS AND METHOD: In a prospective study 59 children admitted to our department for tonsillectomy were each allocated to one of three groups according to how many episodes of acute tonsillitis they had been suffering from per year prior to admission: group 1, 0 episodes of tonsillitis/year; group 2, 1 or 2 episodes/year; group 3, >2 episodes/year. These groups were then compared with the diagnoses yielded by histological examination of the excised tonsils, which were classified into (1) pure hyperplasia; (2) chronic inflammatory tonsillitis; (3) hyperplasia and chronic inflammatory hyperplasia; and (4) chronic inflammation with peritonsillar scarring. RESULTS: In group 1 (n=23) pure hyperplasia was found in only 2 cases, while the tonsils of all other children were affected by chronic inflammatory tissue changes, either alone or in association with hyperplasia. In groups 2 und 3 most tonsillar specimens showed histological characteristics of chronic inflammation, but non-inflammatory hyperplasia alone was also found in 5 cases. CONCLUSION: There is no correlation between the medical history of children undergoing tonsillectomy and the histological diagnosis. In other words, the medical history does not appear to be an appropriate way of reaching a differential diagnosis between non-inflammatory hyperplasia and chronic tonsillitis. This means that tonsillotomy may well leave remnants of chronically inflamed tonsillar tissue in place. Appropriate counselling of the parents seems to be necessary. PMID- 17333039 TI - [Investigation of the mechanisms involved in isolated orbital floor fracture. Simulation using a finite element model of the human skull]. AB - BACKGROUND: Isolated orbital floor fractures make up a significant proportion of all facial injuries, but the mechanism involved in these injuries to the orbital walls (blow-out fractures) has not yet been completely defined. Two theories have been described, which seem to be mutually exclusive. According to the hydraulic pressure theory, the kinetic energy of the blow is transferred via the incompressible eye tissue to the floor of the orbita, which in turn fractures. The buckling force theory, in contrast, explains these fractures as the result of bending and shear stresses arising from kinetic energy act directly on the orbital rim. MATERIALS AND METHODS: With the aim of elucidating the mechanism of injury, we constructed a simplified finite-element model of the human orbita by 3D optical scanning of a human skull obtained after an autopsy examination. We created a generic approximation model based on empiric data derived from femoral fractures and reported in the literature. Several experiments were conducted to test both the above hypotheses by direct and indirect application of kinetic energy. RESULTS: We simulated different types of shear stress with the finite element model of the skull. The calculated points of maximum pressure were all within the orbital floor. CONCLUSION: The simulation showed that both mechanisms can lead to fractures, as also documented by recent studies. The generation of a finite-element model and simulation of stresses were initially useful in establishing a method. More detailed studies on the empiric data relating to the various structures and more extensive determination and measurement of different skull and/or orbita geometries are needed before we can achieve a model in which the mechanical attributes of the structures involved are reproduced with closer approximation to the real-life situation. PMID- 17333041 TI - [Vestibular paroxysmia. A rare but important differential diagnosis]. AB - The diagnosis and treatment of vertigo are very common in ear nose and throat medicine and neurology. As our case report demonstrates, an interdisciplinary approach is often useful for finding the correct diagnosis. Diagnosing disabling positional vertigo now seems uncomplicated using special MRI. More important is the history of frequent, short-term vertigo, sometimes accompanied by tinnitus. In analogy to trigeminal neuralgia, treatment should be started with carbamazepine or similar drugs. If unsuccessful, microvascular decompression as a neurosurgical intervention is recommended. PMID- 17333042 TI - [Internal jugular vein thrombosis as a paraneoplastic syndrome]. AB - Thrombosis of the internal jugular vein is a rare form of deep vein thrombosis with potentially life threatening complications. We report on a 46-year-old male presenting with dysphagia and neck swelling. An extensive thrombosis of the internal jugular vein was found on ultrasound of the neck. An interdisciplinary workup revealed an occult gastric carcinoma. This case demonstrates that concomitant malignancies may contribute to a thrombosis of the internal jugular vein, which is then the primary symptom presented by the patient. PMID- 17333044 TI - [Survival with distant metastatic disease in head and neck cancer. A retrospective analysis]. AB - QUESTIONS: The objective of this retrospective analysis was to investigate parameters with a potential impact on survival in a collective of 114 patients with distant metastatic disease after head and neck cancer. PATIENTS AND METHODS: The primary endpoint was the survival with distant metastatic disease, the secondary endpoint was overall survival. Primary therapy, local recurrence, second neoplasms, palliative chemotherapy (CHT) and radiotherapy (RT), as well as Karnofsky performance status (KPS) at the time of diagnosis of the metastases were analyzed as potential impact parameters using the log-rank test with subsequent Cox regression analysis. RESULTS: Palliative CHT (P=0.0020) and KPS (P=0.0011) had a significant positive impact on the median survival probability with metastases (8.2 months) using the log-rank test, KPS at the time of diagnosis of metastases remained as an independent prognostic parameter in the Cox regression (P=0.0013). Primary therapy, local tumor control and KPS had a significant positive influence on the median overall survival probability (18.5 months) univariately (P=0.0139, P=0.0106, P= 0.0096) and multivariately (P=0.0123, and P=0.0063, P=0.0197, respectively). CONCLUSIONS: KPS at the time of diagnosis of metastases is an independent prognostic parameter for both endpoints. Lacking evidence for life prolongation, palliative therapies should therefore first and foremost focus on the stabilization of the KPS. PMID- 17333045 TI - [Acupuncture in ear, nose and throat medicine: part 2. Diseases of the nose, paranasal sinuses and ears]. AB - The second part of the article deals with the use ear and body acupuncture for disorders of the nose, the paranasal sinuses and the ear, including the cerebral structures of the hearing system. It is pointed out that acupuncture must be based on orthodox medical diagnosis. The reader will learn when acupuncture may serve as a "stand alone" method, when it may be an additional option supporting orthodox therapy and when it must not be applied. PMID- 17333046 TI - [Angioneurotic edema of the head and neck in association with ACE inhibitors]. AB - BACKGROUND: ACE-inhibitors are said to cause angioneurotic edema. In spite of the fact that patients with acute angioedema of the head and neck region are usually admitted to an ENT department, there is only limited information available in the otorhinolaryngological literature on the frequency, risk of recurrent episodes and clinical significance of ACE inhibitor related angioedema. MATERIAL AND METHODS: The medical histories of all patients admitted to our hospital due to acute angioneurotic edema during the period from 1 January 1988 to 31 December 2001 were reviewed. These were supplemented with the results of a standardized questionnaire filed out by the affected patients and of a non-affected control group. RESULTS: During the observation period. 121 patients were treated for acute angioneurotic edema of the head and neck region. In 34 patients (=28.1%), edema was related to permanent treatment with ACE inhibitors. The overall frequency of angioedema and the percentage of ACE inhibitor related angioedema showed a continuous increase during the study period. There was a latency from the beginning of ACE inhibitor treatment until the first manifestation of angioedema of up to 13 years. In comparison with the group of edema patients without ACE inhibitor treatment, we found a threefold risk of recurrent edema in the ACE group. Women were affected by recurrent episodes more often than men. Until now, any individual assessment of the probable risk of developing an angioneurotic edema during ACE inhibitor treatment appears to be impossible. PMID- 17333047 TI - [Wait and see antibacterial therapy in acute otitis media]. PMID- 17333048 TI - [Surgery of benign tumors of the parotid gland: the value of fine needle aspiration cytology]. AB - BACKGROUND: Fine needle aspiration cytology (FNAC) is a widely used diagnostic tool to evaluate neoplastic or inflammatory tumorous lesions of the salivary glands. This method influences the selection of the modality of surgical treatment. In cases of benign tumors of the parotid gland, a (partial) superficial parotidectomy is usually recommended. However, for tumors other than pleomorphic adenomas (such as cystadenolymphomas, other adenomas, or benign tumor like lesions) this operation is considered an overtreatment because extracapsular satellites are rare and recurrences in case of a capsular lesion are not likely. In such cases, a less extended surgery (enucleation) with lower morbidity is sufficient and can be carried out provided that pleomorphic adenomas and non pleomorphic benign lesions are reliably differentiated prior to surgery. The aim of this study was to evaluate the reliability of the FNAC in differentiating benign tumors of the parotid gland. METHODS: A retrospective evaluation of 160 cases of benign parotid gland tumors was performed and the cytological diagnoses compared with the histomorphological results. A collection of 26 cases with false negative and false-positive results was reevaluated. RESULTS: FNAC showed a sensitivity of 74.2% and a specificity of 89.8% for differentiation between pleomorphic adenomas and non-pleomorphic benign lesions. The predictive value for pleomorphic adenomas was 82.1%, and for non-pleomorphic benign lesions 84.6%. Reevaluation showed higher sensitivity (96.2%), specificity (98.9%), and negative/positive predictive values (97.9% and 98.1%, respectively). DISCUSSION/CONCLUSION: Poor quality and hypocellularity of the cytological smears seem to negatively effect the outcome of the cytological diagnosis. It is concluded that only an accurate diagnosis of non-pleomorphic adenoma or a benign tumor-like lesion, based on an adequate FNAC specimen and assessed by an experienced cytopathologist, can justify tumor enucleation because the risk of pleomorphic adenoma is only 2% under these circumstances. PMID- 17333049 TI - [A young fireman candidate with an abnormal chest x-ray]. AB - An 18-year-old, asymptomatic male underwent a routine chest x-ray examination which showed a pathological result. It revealed a characteristic crescent-like shadow in the right lower lung field, resembling a muslim sword (scimitar), responsible for the name of the underlying disease. Scimitar syndrome is a rare congenital malformation with a wide clinical spectrum ranging from asymptomatic to severe disturbances manifesting in childhood. The typical findings are hypoplasia of the right lung with marked mediastinal shift to the right and dextrocardia, reduced right pulmonary artery perfusion with maintained bronchial connection, anomalous arterial supply to the right lower lobe from the aorta and abnormal draining of the enlarged right pulmonary vein into the pulmonary circulation, producing the characteristic radiographic "scimitar sign". The development of right ventricular failure due to long-standing right ventricular overload and recurrent respiratory infections depend on the severity of anatomical abnormalities and functional disorders, sometimes requiring surgical intervention. Nowadays, sophisticated imaging techniques allow precise and rapid diagnosis of these complex abnormalities and their functional implications. The findings for our patient differed from the classic constellation, with a regular emptying of the enlarged right pulmonary vein into the left atrium, leading to a decreased burden on the central haemodynamics. In our very rare case of a scimitar syndrome variant, the functional disorders were negligible. PMID- 17333050 TI - [Hyponatraemic encephalopathy and rhabdomyolysis. Complications after preparation for colonoscopy with mannitol]. AB - In the preparation for colonoscopy, it is necessary to drink a great deal of often hypo-osmotic fluid. Therefore, the electrolytes and intra- and extracellular water are disequilibrated. Most of the patients tolerate this without any subjective or objective symptoms. In our case, a young male patient suffered from a severe hyponatriaemia with encephalopathy for more than 48 h through the preparation for an elective ambulant colonoscopy with mannite. Furthermore, he developed a rhabdomyolysis (either through lying on the floor in coma for more than 9 h, through the hyponatriaemia itself or through compensation of the hyponatriaemia) that lasted for ca. 1 week. PMID- 17333051 TI - [Diagnostics for pulmonary tuberculosis in adults]. AB - The incidence of pulmonary tuberculosis (TB) is decreasing in Western Europe. However, TB should not be considered to be a rare disease, particularly in immigrants and in immunocompromised persons (i.e. HIV infection). The clinical presentation is often atypical in immunocompromised persons. In general, the extent of the disease is underestimated by the clinical presentation. X-ray and a sequential investigation of three samples of sputum including microscopy, culture and susceptibility testing for the first-line drugs should be obtained. Tuberculin testing is useful in the diagnosis of latent TB and in screening persons with close contact to patients with active disease. New blood tests based on the detection of interferon-g released by antigen specific T-cells have some advantages compared to tuberculin testing. PMID- 17333052 TI - [Myocardial infarct and unstable angina pectoris: diagnostics and therapy]. AB - Acute coronary syndromes include ST-elevation and non-ST elevation myocardial infarction, and unstable angina pectoris. These are characterised by the acute onset of chest pain. For the diagnostic work up in the acute phase, ECG and the assessment of cardiac markers play a central role. For patients with ST elevation, primary interventional therapy is the first choice. For patients with an acute coronary syndrome without ST-elevation, a risk adapted therapeutic strategy should be chosen. High risk patients (elevated troponins, clinical, rhythmological and hemodynamic instability, ST-depression and diabetes mellitus) should be treated by an early invasive approach with angiography performed within 48-72 h. Low risk patients should be treated conservatively. For all patients who are treated interventionally, the administration of an aggressive antiaggregatory therapy including aspirin, clopidogrel, glycoprotein IIb/IIIa inhibitors and heparin is indicated in the acute phase. In the chronic phase, the treatment of cardiovascular risk factors is of paramount importance. PMID- 17333054 TI - [Endocrine disorders and the heart]. AB - Hormonal regulation is not possible without the cardiovascular system, and thus the heart plays a special role not only in the action and synthesis, but also in the distribution of hormones. Severe endocrine disorders with cardiac involvement are often threatening for the patient. The impact of aberrant thyroid function, the sympathetic-adrenal symptoms of which predominantly affect the heart, is well known. Diabetes mellitus and the associated metabolic syndrome are major causes of cardiovascular disease and determine its morbidity and lethality rates. Acromegaly causes a complex cardiomyopathy that may result in cardiac failure refractive to conventional treatment. The excessive production of adrenal hormones in Cushing's syndrome, hyperaldosteronism and pheochromocytoma primarily harms the heart by causing severe hypertension. The same holds true for long standing hyperparathyroidism. Recent prospective studies did not confirm the protective effect of hormone replacement therapy on cardiovascular disease. PMID- 17333055 TI - [The heart in cases of viral, bacterial and parasitic infections]. AB - The heart can be the primary target for a viral, bacterial or parasitic infection (primary myocarditis/inflammatory cardiomyopathy). It can also participate in the "collateral damage" due to toxins, chemo- and cytokines, autoreactive antibodies or the native and acquired immune response through T- and B-cells, monocytes and macrophages (secondary myocarditis/inflammatory cardiomyopathy), when it is not the dominant organ of the disease. Infective agents show remarkable organ specificity: viral infections, toxic and autoreactive processes affect primarily the myocardium and the pericardium, whereas bacterial infections prefer endothelial surfaces and cause endocarditis and, less frequently, pericarditis. They are even discussed as part of the inflammatory process involved in coronary artery disease. Infective agents and their adequate diagnosis and treatment are discussed for these clinical entities according to current guidelines and clinical pathways. PMID- 17333056 TI - [Lowering LDL cholesterol. How much is enough?]. AB - Reducing cholesterol and LDL cholesterol (LDL-C) is one of the few clearly demonstrated principles in the prevention and treatment of arteriosclerosis. LDL C reduction over a number of years to ca. 70 mg/dl can reduce the risk of coronary events by about two thirds. Lipid lowering pharmacotherapy is the more effective the higher the individual risk of the patient is. The therapeutic decision is based on the total risk of the patient. For coronary patients after acute coronary syndrome and/or with diabetes mellitus, a reduction of LDL-C to 70 mg/dl is justified. For patients with "stable" coronary heart disease, a LDL-C level of 100 mg/dl or less should be strived for. Whether diabetes mellitus always indicates a "coronary risk equivalent" and thus justifies a reduction in LDL-C to 100 ml/dl or less, is questionable. PMID- 17333057 TI - [Status of homocysteine reduction in prevention of cardiovascular diseases. HOPE 2 study (Heart Outcomes Prevention Evaluation)]. PMID- 17333058 TI - [Metabolic syndrome--which nutrition recommendations apply?]. PMID- 17333059 TI - [The ailments of Johann W. On the 175th anniversary of Goethe's death]. PMID- 17333060 TI - [In memoriam: Dr. Eberhard Zohlen]. PMID- 17333061 TI - [Care of complex knee joint injuries in patients with polytrauma]. PMID- 17333062 TI - [Orthopedic and trauma surgery in the German DRG System 2007]. AB - BACKGROUND: The German Diagnosis-Related Groups (DRG) System was further developed into its 2007 version. For orthopedic and trauma surgery, significant changes were made in terms of the coding of diagnoses and medical procedures, as well as in the DRG structure itself. The German Societies for Trauma Surgery and for Orthopedics and Orthopedic Surgery (Deutsch Gesellschaft fur Unfallchirurgie, DGU; and Deutsche Gesellschaft fur Orthopadie und Orthopadische Chirurgie, DGOOC) once again cooperated constructively with the German DRG Institute InEK. RESULTS: Among other innovations, new International Classification of Diseases (ICD) codes for second-degree burns were implemented. Procedure codes for joint operations, endoprosthetic-surgery and spine surgery were restructured. Furthermore, a specific code for septic surgery was introduced in 2007. In addition, the DRG structure was improved. Case allocation of patients with more than one significant operation was established. Further DRG subdivisions were established according to the patients age and the Patient Clinical Complexity Level (PCCL). CONCLUSIONS: DRG developments for 2007 have improved appropriate case allocation, but once again increased the system's complexity. Clinicians need an ever growing amount of specific coding know-how. Still, further adjustments to the German DRG system are required to allow for a correct allocation of cases and funds. PMID- 17333063 TI - [Complex knee injury in polytraumatized patients]. AB - In polytraumatized patients severe joint injuries represent a special entity because their management is complex and lengthy. The surgeon must decide if limb salvage is indicated and which further surgical steps have to be instituted. The decision for amputation is based on the patient's general condition and the soft tissue and neurovascular injury. Scoring systems are useful for decision making. Limb salvage is associated with a multistage surgical approach. Priority is given to restoration of sufficient blood supply and soft tissue repair; the indication for fasciotomy covers a wide field. To avoid further compromise to soft tissue and perfusion, temporary joint and fracture stabilization is required. Definitive surgery has to be delayed until the 2 week period, starting between the fifth and tenth day after trauma. PMID- 17333064 TI - [Cardiac MR imaging in arrhythmogenic heart diseases]. AB - INTRODUCTION: Cardiac arrhythmias are assessed with a combination of history, clinical examination, electrocardiogram, Holter monitor, if necessary supplemented by invasive cardiac electrophysiology. In ischemic heart disease (IHD) coronary angiography is performed in addition. METHODS: Echocardiography is usually the primary imaging modality. MRI is increasingly recognized as an important investigation allowing more accurate cardiac morphological and functional assessment. RESULTS: Approximately one-fifth of deaths in Western countries are due to sudden cardiac death, 80% of which are caused by arrhythmias. Typical causes range from diseases with high prevalence (IHD in men 30%) to myocarditis (prevalence 1-9%) and rare cardiomyopathies (prevalence HCM 0.2%, ARVC 0.02%, Brugada syndrome approx. 0.5%). The characteristic MRI features of arrhythmogenic diseases and the new aspects of characteristic distribution of late enhancement allow etiologic classification and differential diagnosis. CONCLUSION: MRI represents an important tool for detection of the underlying cause and for risk stratification in many diseases associated with arrhythmias. PMID- 17333067 TI - [Gene therapy for treatment of acute inflammatory immune response]. AB - Acute inflammation and the innate immune response to severe tissue trauma continue to pose a critical pathophysiological challenge in the intensive care regimen. Advances in the development of improved gene therapeutics and their application in diverse animal models of acute inflammation have shown promising results in reducing both morbidity and mortality. The introduction of inflammatory antagonists, by either viral or non-viral vectors, has thereby proven to play a significant role in determining the overall outcome. Recent findings of utilizing the functional characteristics of immunocompetent cells (e.g. dendritic cells) in combination with the gene therapy-induced overexpression of anti-inflammatory target proteins have significantly expanded this gene therapeutic spectrum. The results from diverse experiments in our own murine model of sepsis, in connection with findings from various other analogous international studies, have demonstrated great potential to revolutionize the clinical treatment concept and prevention of acute inflammatory diseases. PMID- 17333066 TI - [The relevance of the inflammatory response in the injured brain]. AB - Research efforts in recent years have defined traumatic brain injury (TBI) as a predominantly immunological and inflammatory disorder. This perception is based on the fact that the overwhelming neuroinflammatory response in the injured brain contributes to the development of posttraumatic edema and to neuropathological sequelae which are, in large part, responsible for the adverse outcome. While the "key" mediators of neuroinflammation, such as the cytokine cascade and the complement system, have been clearly defined by studies in experimental TBI models, their exact pathways of interaction and pathophysiological implications remain to be further elucidated. This lack of knowledge is partially due to the concept of a "dual role" of the neuroinflammatory response after TBI. This notion implies that specific inflammatory molecules may mediate diverse functions depending on their local concentration and kinetics of expression in the injured brain. The inflammation-induced effects range from beneficial aspects of neuroprotection to detrimental neurotoxicity. The lack of success in pushing anti inflammatory therapeutic concepts from"bench to bedside" for patients with severe TBI strengthens the further need for advances in basic research on the molecular aspects of the neuroinflammatory network in the injured brain. The present review summarizes the current knowledge from experimental studies in this field of research and discusses potential future targets of investigation. PMID- 17333068 TI - [Use of bone marrow mesenchymal stem cells for ex vivo cartilage regeneration]. AB - Articular cartilage disorders and injuries often result in lifelong chronic pain and compromised quality of life. When it comes to local articular cartilage defects, modern medicine is limited to short-term pain relief and inflammation control. In extreme cases the affected tissue is surgically removed and replaced by a synthetic prosthesis of limited durability. Cell-based therapies to regenerate articular cartilage have been in use since 1994. Such therapies provide a healthy population of cells to the injured site and require differentiated chondrocytes from the uninjured site as base material. Their usage often leads to donor site morbidity and they generate rigid fibrous cartilage where more flexible hyaline cartilage is required. The major restrictive factors for such methods are inadequate number and limited proliferation capacity of chondrocytes in vitro. Tissue engineering of adult marrow stromal cells/mesenchymal stem cells (MSCs) with their almost unlimited proliferation potential and proven capability to differentiate into chondrocytes for ex vivo generation of cartilage tissue still remains a vision. For optimal harnessing of MSCs as chondroprogenitor cells, basic background information regarding commitment to the lineage, cartilage differentiation and the regulatory factors and molecules involved is essential. PMID- 17333069 TI - [Biomechanical consequences of variations in artificial disc positioning. A finite element study on the lumbar spine]. AB - Artificial disc prostheses are becoming more and more attractive for the treatment of degenerative disc diseases using non-fusion techniques. However, the influence of disc position within the intersegmental space on lumbar biomechanics has scarcely been investigated. A validated finite element model of the lumbar spine was used to investigate the effects of non-ideal implant positioning and orientation, which are more likely to occur using ventrolateral approaches. The model predicts, especially for lateral eccentricities, strongly increased lumbar loads. Therefore, great care should be taken in placing the implant in an optimal position. PMID- 17333070 TI - [Loads acting on orthopaedic implants. Measurements and practical applications]. AB - The loads measured at instrumented joint replacements and other orthopaedic implants allow the optimization of their stability, wear properties, fixation stability and kinematic properties prior to clinical applications. The data obtained also indicate which activities cause very high loads and should be avoided by the patients in order not to endanger the long-term success of the implant. In addition, physiotherapy after joint arthroplasty and fractures can be further improved on the basis of these data. The technical principles for such measurements are summarized and examples for the design of load measuring instrumented implants are presented. The most important results are presented based on the measurements taken at the hip and shoulder joints, internal spinal fixation devices, vertebral body replacements and knee joints. Using this data, many practical conclusions are drawn. Due to the huge amount of data obtained from the hip, most practical advise can be provided to patients with replacement or disorders involving this joint. PMID- 17333071 TI - [Musculoskeletal load analysis. A biomechanical explanation for clinical results- and more?]. AB - Mechanical loading of the lower extremities due to muscle and joint contact forces plays an important role in orthopaedic and trauma surgery. Detailed, patient specific information on the in vivo forces and their distribution is, however, currently not readily available to the surgeon in clinical routine. The goal of this study was to elucidate the relationship between the position of the cup and the musculoskeletal loading conditions at the hip using validated analyses, and further, to evaluate the predictions of the biomechanical conditions against the results of a clinical study. The results indicate that restoring the anatomical hip centre to its anatomical mediolateral position could help to reduce joint loads and add to the longevity of the reconstruction. The routine use of validated analyses of musculoskeletal loading conditions, such as in the presented example using standardised pre-operative planning and sound intra-operative decision support systems, could contribute to securing a high standard in patient treatment. PMID- 17333072 TI - [Epithelial invasion after eye ball rupture]. PMID- 17333074 TI - [The suitability of hyaluronic acid in the therapy of deep upper lid sulcus in the anophthalmic orbit]. AB - BACKGROUND: For correcting deep persisting upper lid sulcus in cases of enucleation or evisceration, a subperiostal implant can be used to lift the entire contents of the orbit, or dermis fat can be implanted into the lid. However, there is no optimal surgical procedure in these cases. PATIENTS AND METHODS: Five patients showing a deep, persisting, upper lid sulcus were treated with hyaluronic acid. The resorption of the acid was documented by photography every 4 weeks. Four out of the five patients did well; one patient lost the acid completely after 1-2 days and showed signs of inflammation. The time for resorption to occur varied from 4.5 to 11 months. Two patients showed better moistening of the prostheses. CONCLUSION: This pilot study shows that cross linked hyaluronic acid can be used for the temporary treatment of the deep upper lid sulcus. Further studies should be carried out using a larger number of patients in order to obtain more detailed information. PMID- 17333073 TI - [A comparison of rebound tonometry (ICare) with TonoPenXL and Goldmann applanation tonometry]. AB - BACKGROUND: Goldmann applanation tonometry and dynamic contour tonometry (PASCAL) are two well established slit lamp mounted tonometric methods. Intraocular pressure measurement in bedridden patients and children is often only possible using hand held tonometers (TonoPenXL, Perkins tonometer, Draeger tonometer). This study was performed to evaluate the hand held ICare tonometer, which is based on the rebound method. METHODS: A total of 102 eyes were examined by two highly experienced ophthalmologists for: 1) ophthalmological status, 2) central corneal power (Zeiss IOL-Master), 3) central corneal thickness (Tomey ultrasound pachymetry, five successive measurements, SD<5%), 4) intraocular pressure (IOP) measurement with the Goldmann applantation tonometer (GAT) 1x, 5) TonoPenXL (1x), 6) ICare with three successive measurement series of 6 single measurements. RESULTS: The mean IOP(GAT) was 13.2+/-3.0 mmHg compared with the mean IOP(TonoPenXL) (13.4+/-3.1 mmHg) and with the IOP(ICare) (mean value of first measurement series: 13.4+/-3.1 mmHg). The series of measurements with the ICare showed a tonography effect (decrease of IOP from 14.6 mmHg at the first measurement and 14.2 mmHg at the second to 14.0 at the third measurement). The ICare-measurements were highly reliable (Cronbach's alpha=0.974) and showed a good correlation between the measurement series (r=0.592-0.642; p<0.001). There was a great intra-individual variability of up to 17 mmHg between the GAT, TonoPenXL and ICare methods. CONCLUSIONS: The ICare tonometer is easy to handle and high reliability. The data are comparable with those from the Goldmann tonometer. A tonography effect of 0.6 mmHg in the successive measurement series was found. PMID- 17333075 TI - [Ex- und reimplantation of intracorneal ring segments with the support of femtosecond laser, Femtec, for the treatment of progressive keratoconus]. AB - Implanted intracorneal ring segments (ICRS) led to a steepening of the cornea and an increase in visual deterioration. Thanks to the femtosecond laser, we can now prepare implantation tunnels intrastromally with mum precision. Therefore, we explanted the original ring segments. After a waiting period, we prepared a second implantation tunnel above the first using the femtosecond laser and implanted new ICRS. The conus was considerably flattened and shifted, and vision improved significantly. PMID- 17333076 TI - [Adipocytokines as driving forces in rheumatoid arthritis]. PMID- 17333077 TI - [Comorbidity in patients with chronic low back pain]. AB - BACKGROUND: Studies concerning comorbidity in patients with chronic low back pain and its correlation to the stage of chronification are rare. METHODS: This case control study (matched-pair analysis) examines the number and specificity of comorbidity as well as the extent of disability due to comorbidity in 51 patients with chronic low back pain compared to age- and sex-matched control persons. Moreover, the correlation of comorbidity and the stage of chronification was analysed in these patients. RESULTS: Patients with chronic low back pain had significantly more comorbidities and a higher disability due to comorbidity compared to the control persons. The higher the stage of chronification according to the Mainz Pain Staging System (MPSS) the higher was the number of comorbidities. CONCLUSION: Comorbidity should be given due consideration when evaluating diagnosis, therapy, prognosis and therapy outcome in patients with chronic low back pain. PMID- 17333078 TI - [Opioid availability in Kenya: workshop and project]. PMID- 17333080 TI - Molecular diagnosis of pulmonary tuberculosis by automated extraction and real time PCR on non-decontaminated pulmonary specimens. PMID- 17333079 TI - Bioinformatic analysis of human CNS-expressed ion channels as candidates for episodic nervous system disorders. AB - As monogenic forms of episodic nervous system disorders are often caused by ion channel mutations, we looked for features of human central nervous system (CNS) expressed ion channels that further our understanding of those phenotypes. To this end, we compared human ion channels with other CNS-expressed genes, which we categorized according to the existence of transmembrane domains. When looking at the phylogenetic distribution of these genes, we observed an increased percentage of ion channels that exist in vertebrate genomes while missing in invertebrate genomes. Because we hypothesized that this pattern may relate to a more specific expression, we searched for characteristics of ion channels that indicate a tighter expression regulation. We found that ion channels have longer intron and protein sequences, features typical of genes with more specific expression. In addition, ion channels have increased human-rodent conservation around their transcription start site, as indicated by a higher fraction of conserved noncoding regions. This points to a high relevance of mutations that regulate ion channel expression. When we finally asked whether vertebrate-specific diversification is also displayed by non-ion channel genes with important roles in the CNS, we found a similar phylogenetic distribution. This concordant phylogenetic pattern suggests that vertebrate-specific adaptations may account for a large part of the shared genetic basis of episodic CNS disorders, including monogenic and genetically complex disease manifestations. Consequently, this phylogenetic pattern may contribute to the prioritization of candidate genes in human genetic studies of episodic CNS disorders. PMID- 17333081 TI - Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting. AB - The study presented here was performed in order to create a rule that identifies subjects at high risk for invasive candidiasis in the intensive care setting. Retrospective review and statistical modelling were carried out on 2,890 patients who stayed at least 4 days in nine hospitals in the USA and Brazil; the overall incidence of invasive candidiasis in this group was 3% (88 cases). The best performing rule was as follows: Any systemic antibiotic (days 1-3) OR presence of a central venous catheter (days 1-3) AND at least TWO of the following-total parenteral nutrition (days 1-3), any dialysis (days 1-3), any major surgery (days -7-0), pancreatitis (days -7-0), any use of steroids (days -7-3), or use of other immunosuppressive agents (days -7-0). The rate of invasive candidiasis among patients meeting the rule was 9.9%, capturing 34% of cases in the units, with the following performance: relative risk 4.36, sensitivity 0.34, specificity 0.90, positive predictive value 0.01, and negative predictive value 0.97. The rule may identify patients at high risk of invasive candidiasis. PMID- 17333082 TI - MR imaging findings of pyogenic bacterial myositis (pyomyositis) in patients with local muscle trauma: illustrative cases. AB - Pyogenic myositis (pyomyositis) represents a bacterial infection of muscle, usually caused by Staphylococcus aureus that is endemic in tropical regions. Pyomyositis commonly affects patients who are immunocompromised or who have underlying chronic disorders. Lower extremity localization of infection is typical. The most common pattern of disease, however, appears to be a solitary abscess in the quadriceps musculature. Delay in accurate diagnosis is frequent and clinical deterioration can be precipitous. In view of the high associated morbidity, early imaging to detect, localize, and define disease extent is important. Magnetic resonance imaging (MRI) plays a key role in the definitive diagnosis of pyomyositis. This article provides a pictorial illustration of the spectrum of MRI findings associated with pyogenic myositis. PMID- 17333083 TI - Infarcted splenule--a case report. AB - A 38-year-old woman presented with abdominal pain and left shoulder pain. A computed tomography scan was obtained, which demonstrated a rounded soft tissue density with surrounding stranding. It was interpreted as an infarcted splenule. Due to the increasing severity of the patient's symptoms, a laparoscopic exploration was performed. Pathology demonstrated an infarcted splenule. As infarcted splenules are rare, an understanding of its pathogenesis and familiarity with the corresponding imaging findings may be helpful for its diagnosis in the patient with the appropriate clinical scenario. It is important to recognize this entity as a cause of abdominal pain that can be managed nonsurgically. PMID- 17333084 TI - CT imaging of acute E. Coli-related colitis. AB - Patients with abdominal pain and bloody diarrhea often present in the acute setting to the emergency department for evaluation. After the appropriate clinical assessment, cross-sectional imaging is often utilized to evaluate for the severity of the disease. Although a wide spectrum of findings may be seen, diffuse colonic mural thickening, consistent with pancolitis, is most common. We report an Escherichia coli 0157:H7-related pancolitis in a patient with spinach intake linked to the recent outbreak. PMID- 17333085 TI - A single fracture in the atlas ring: report of two cases and a review of the literature. AB - Atlas fractures commonly present more than two breaks in its ring structure because of the unique anatomy and the mechanism of injury. The incidence of a single break in the atlas ring is exceedingly rare. However, we encountered two cases of a single fracture of the atlas. One patient was struck by a falling tree on the right side of the head and the other was involved in a motor vehicle accident. Radiographs of the cervical spine failed to show a single fracture or other abnormalities. Computed tomography demonstrated the single fracture. The patients were treated conservatively with a cervical collar, and they both recovered completely. In this article, we present two cases of a single fracture of the atlas with a review of the literature. PMID- 17333086 TI - Segmentation of retinal blood vessels using a novel clustering algorithm (RACAL) with a partial supervision strategy. AB - In this paper, segmentation of blood vessels from colour retinal images using a novel clustering algorithm with a partial supervision strategy is proposed. The proposed clustering algorithm, which is a RAdius based Clustering ALgorithm (RACAL), uses a distance based principle to map the distributions of the data by utilising the premise that clusters are determined by a distance parameter, without having to specify the number of clusters. Additionally, the proposed clustering algorithm is enhanced with a partial supervision strategy and it is demonstrated that it is able to segment blood vessels of small diameters and low contrasts. Results are compared with those from the KNN classifier and show that the proposed RACAL performs better than the KNN in case of abnormal images as it succeeds in segmenting small and low contrast blood vessels, while it achieves comparable results for normal images. For automation process, RACAL can be used as a classifier and results show that it performs better than the KNN classifier in both normal and abnormal images. PMID- 17333087 TI - A paediatric supratentorial primitive neuroectodermal tumour associated with malignant astrocytic transformation and a clonal origin of both components. AB - The case of a 7-year-old boy suffering from a supratentorial primitive neuroectodermal tumour (sPNET) at the age of 5 is presented. The tumour has been characterized by astrocytic areas within the sPNET revealing malignant transformation up to a multiform glioblastoma during the course of the disease. The clonal origin of both tumour components was established by loss of heterozygosity (LOH) analysis. Clinically, the tumour showed an aggressive biological behaviour with two recurrences. We discuss this very rare case and the first description of the clonal origin of distinct and distinguishable tumour components taking into consideration published literature. PMID- 17333088 TI - Comparative cost-minimisation of oral and intravenous chemotherapy for first-line treatment of non-small cell lung cancer in the UK NHS system. AB - The National Institute for Health and Clinical Excellence recommends vinorelbine (VNB), paclitaxel, docetaxel, and gemcitabine in the treatment of non-small cell lung cancer. An economic model was prepared to determine the comparative cost of these agents, including the new oral formulation of VNB from a United Kingdom National Health System perspective. Clinical effectiveness was determined from published trials. Costs of drug acquisition, administration, toxicity management, and patient transportation costs were calculated from reference publications. A Markov model was used to estimate the cost per patient over 52 weeks. Intravenous VNB, gemcitabine, paclitaxel, and docetaxel incur annual follow-up costs of 3,746 pounds, 5,332 pounds, 5,977 pounds, and 6,766 pounds, respectively, while oral VNB with outpatient administration on d1, and self-administration at home on d8 every 21 days has a cost per patient per year of 2,888 pounds. Oral VNB allows further hospital resources savings. PMID- 17333089 TI - Cost-effectiveness of heptavalent conjugate pneumococcal vaccine (Prevenar) in Germany: considering a high-risk population and herd immunity effects. AB - In Germany, the seven-valent conjugate vaccine Prevenar is recommended for use in children at high risk of pneumococcal disease. Recent data suggest that giving conjugate vaccine to all children may lead to a decline in pneumococcal disease in unvaccinated adults, a phenomenon known as herd immunity. This analysis evaluated the cost and economic consequences in Germany of vaccinating (1) children at high risk, (2) all children when considering only benefits for vaccinated individuals and (3) all children when also considering herd immunity benefits. Costs in the model included vaccination, management of meningitis, bacteraemia, pneumonia and acute otitis media, insurance payments to parents and the costs of care for long-term disabilities. The model estimated that the cost effectiveness of vaccination would be 38,222 euros per life year gained in children at high risk and 100,636 euros per life year gained in all children when not considering herd immunity. When considering herd immunity effects, the model estimated that offering vaccination for all children would reduce adult deaths by 3,027 per year, and vaccination would be broadly cost neutral. The findings are sensitive to the effect of conjugate vaccine on the rates of pneumonia and invasive disease in the elderly. If the herd immunity effect of conjugate vaccination in Germany is similar to that observed elsewhere, offering vaccine to all children will be more attractive than the current policy of restricting vaccination to children at high risk of pneumococcal disease. PMID- 17333090 TI - Infant brain subjected to oscillatory loading: material differentiation, properties, and interface conditions. AB - Past research into brain injury biomechanics has focussed on short duration impulsive events as opposed to the oscillatory loadings associated with Shaken Baby Syndrome (SBS). A series of 2D finite element models of an axial slice of the infant head were created to provide qualitative information on the behaviour of the brain during shaking. The test series explored variations in subarachnoid cerebrospinal fluid (CSF) representation, brain matter stiffness, dissipation, and nonlinearity, and differentiation of brain matter type. A new method of CSF modelling based on Reynolds lubrication theory was included to provide a more realistic brain-CSF interaction. The results indicate that solid CSF representation for this load regime misrepresents the phase lag of displacement, and that the volume of subarachnoid CSF, and inclusion of thickness variations due to gyri, are important to the resultant behavior. Stress concentrations in the deep brain are reduced by fluid redistribution and gyral contact, while inclusion of the pia mater significantly reduces cortex contact strains. These results provide direction for future modelling of SBS. PMID- 17333091 TI - Comparative studies of phenotypic and genetic characteristics between two desulfurizing isolates of Rhodococcus erythropolis and the well-characterized R. erythropolis strain IGTS8. AB - Two Rhodococcus erythropolis isolates, named A66 and A69, together with the well characterized R. erythropolis strain IGTS8 were compared biochemically and genetically. Both isolates, like strain IGTS8, desulfurized DBT to 2 hydroxybiphenyl (2-HBP), following the 4S pathway of desulfurization. Strain IGTS8 showed the highest (81.5%) desulfurization activity in a medium containing DBT at 30 degrees C. Strain A66 showed approximately the same desulfurization activity either when incubated at 30 degrees C or at 37 degrees C, while strain A69 showed an increase of desulfurization efficiency (up to 79%) when incubated at 37 degrees C. Strains A66 and A69 were also able to grow using various organosulfur or organonitrogen-compounds as the sole sulfur or nitrogen sources. The biological responses of A66, A69 and IGTS8 strains to a series of mutagens and environmental agents were evaluated, trying to mimic actual circumstances involved in exposure/handling of microorganisms during petroleum biorefining. The results showed that strains A69 and IGTS8 were much more resistant to UVC treatment than A66. The three desulfurization genes (dszA, dszB and dszC) present in strains A66 and A69 were partially characterized. They seem to be located on a plasmid, not only in the strain IGTS8, but also in A66 and A69. PCR amplification was observed using specific primers for dsz genes in all the strains tested; however, no amplification product was observed using primers for carbazole (car) or quinoline (qor) metabolisms. All this information contributes to broaden our knowledge concerning both the desulfurization of DBT and the degradation of organonitrogen compounds within the R. erythropolis species. PMID- 17333092 TI - Effect of the cellulose-binding domain on the catalytic activity of a beta glucosidase from Saccharomycopsis fibuligera. AB - Enzyme engineering was performed to link the beta-glucosidase enzyme (BGL1) from Saccharomycopsis fibuligera to the cellulose-binding domain (CBD2) of Trichoderma reesei cellobiohydrolase (CBHII) to investigate the effect of a fungal CBD on the enzymatic characteristics of this non-cellulolytic yeast enzyme. Recombinant enzymes were constructed with single and double copies of CBD2 fused at the N terminus of BGL1 to mimic the two-domain organization displayed by cellulolytic enzymes in nature. The engineered S. fibuligera beta-glucosidases were expressed in Saccharomyces cerevisiae under the control of phosphoglycerate-kinase-1 promoter (PGK1 ( P )) and terminator (PGK1 ( T )) and yeast mating pheromone alpha-factor secretion signal (MFalpha1 ( S )). The secreted enzymes were purified and characterized using a range of cellulosic and non-cellulosic substrates to illustrate the effect of the CBD on their enzymatic activity. The results indicated that the recombinant enzymes of BGL1 displayed a 2-4-fold increase in their hydrolytic activity toward cellulosic substrates like avicel, amorphous cellulose, bacterial microcrystalline cellulose, and carboxy methyl cellulose in comparison with the native enzyme. The organization of the CBD in these recombinant enzymes also resulted in enhanced substrate affinity, molecular flexibility and synergistic activity, thereby improving the ability of the enzymes to act on and hydrolyze cellulosic substrates, as characterized by adsorption, kinetics, thermal stability, and scanning electron microscopic analyses. PMID- 17333093 TI - Biodegradation of nicotine from tobacco waste extract by Ochrobactrum intermedium DN2. AB - Ochrobactrum intermedium DN2 was used to degrade nicotine in tobacco waste extracts. The optimal temperature and pH of nicotine degradation by strain DN2 was 30-37 degrees C and 7.0, respectively. Under these optimal conditions, the average degradation rate of nicotine in a 30L fed-batch culture was 140.5 mg 1( 1) h(-1). The results of this study indicate that strain DN2 may be useful for reducing the nicotine content of reconstituted tobacco. PMID- 17333094 TI - Choroideremia carriers maintain a normal electro-oculogram (EOG). AB - PURPOSE: To assess the functional integrity of the retinal pigment epithelium and outer retina in choroideremia (CHM) carriers with confirmed mutations in the REP 1 gene, by recording the EOG. METHODS: The visual function of 17 choroideremia carriers ages 25-61 was assessed by determining their Snellen visual acuity and by recording the Arden ratio of the EOG. The 15 exons of the CHM gene were PCR amplified from DNA from each of the carriers and their sequences were compared to the normal sequence to identify mutations. RESULTS: The 17 CHM carriers had normal logMAR visual acuity (average of 0.07: Snellen equivalent of 20/25; with no acuities lower than 20/40). The average of the Arden ratio recorded from the 17 carriers was 2.71, which is not significantly different from the average value of 2.46 recorded in our lab. Fundus examination revealed mottled areas of chorioretinal degeneration consistent with the carrier status of CHM. Mutations in the CHM gene were identified in all CHM carriers by sequencing. CONCLUSIONS: Whereas clinical observation suggests that progressive fundus changes are present in female carriers, these carriers do not show a change in the Arden ratio of the EOG over the ages studied (25-61 years). PMID- 17333095 TI - Activity of the Akt-dependent anabolic and catabolic pathways in muscle and liver samples in cancer-related cachexia. AB - In animal models of cachexia, alterations in the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway have been demonstrated in atrophying skeletal muscles. Therefore, we assessed the activity of proteins in this pathway in muscle and liver biopsies from 16 patients undergoing pancreatectomy for suspect of carcinoma. Patients were divided in a non-cachectic or cachectic group according to their weight loss before operation. Extracts of skeletal muscle and liver tissue from eight cachectic patients with pancreas carcinoma and eight non cachectic patients were analysed by Western blotting using pan- and phospho specific antibodies directed against eight important signal transduction proteins of the PI3-K/Akt pathway. Muscle samples from cachectic patients revealed significantly decreased levels of myosin heavy chain (-45%) and actin (-18%) in comparison to non-cachectic samples. Akt protein level was decreased by -55%. The abundance and/or phosphorylation of the transcription factors Foxo1 and Foxo3a were reduced by up to fourfold in muscle biopsies from cachectic patients. Various decreases of the phosphorylated forms of the protein kinases mTOR (-82%) and p70S6K (-39%) were found. In contrast to skeletal muscle, cachexia is associated with a significant increase in phosphorylated Akt level in the liver samples with a general activation of the PI3-K/Akt cascade. Our study demonstrates a cachexia-associated loss of Akt-dependent signalling in human skeletal muscle with decreased activity of regulators of protein synthesis and a disinhibition of protein degradation. PMID- 17333096 TI - Adoptive precursor cell therapy to enhance immune reconstitution after hematopoietic stem cell transplantation. AB - Strategies to enhance post-transplant immune reconstitution without aggravating graft-vs-host disease (GVHD) can improve the outcome of allogeneic hematopoietic stem cell transplantation. Recent preclinical studies demonstrated that the use of T cell depleted allografts supplemented with committed progenitor cells (vs stem cells only) allows enhanced immune reconstitution of specific hematopoietic lineages including myeloid, B, T, and natural killer lineages in the absence of GVHD. This novel adoptive therapy resulted in significantly improved resistance to microbial pathogens and could, in some cases, even mediate tumor immunity. Clinical protocols using adoptive transfer of committed hematopoietic progenitor cells are currently being evaluated. PMID- 17333097 TI - Effect of the angiotensinogen genotype on experimental hypertension in mice. AB - Polymorphisms of the angiotensinogen (Agt) gene may affect blood pressure. We used a mouse model to test for the role of the Agt genotype in low-renin or high renin forms of hypertension. Mice bearing one, two, three, or four copies of the Agt gene underwent renal artery clipping to induce high-renin two-kidney, one clip renovascular hypertension (2K1C), or uninephrectomy, salt loading, and application of deoxycorticosterone-acetate (DOCA) pellets to induce low-renin mineralocorticoid hypertension. Appropriate control animals were also studied. Blood pressure was measured by tail cuff as well as by direct intra-arterial recordings. There was a small effect of the Agt genotype on baseline blood pressure before induction of hypertension. The extent of 2K1C hypertension was not affected by the genotype. In contrast, there was a marked gene-dose effect on DOCA-hypertension (21.2 mmHg over all genotypes). Treatment of DOCA mice with the angiotensin II type 1 receptor antagonist abolished the genotype effect on blood pressure and left ventricular hypertrophy. There was a trend towards less suppression of endogenous aldosterone by DOCA treatment with increasing number of Agt gene copies. We conclude that the Agt genotype exerts a marked effect on blood pressure in a low-renin form of hypertension but no effect in the face of stimulated renin, at least in mice. PMID- 17333098 TI - Normative psychomotor vigilance task performance in children ages 6 to 11--the Tucson Children's Assessment of Sleep Apnea (TuCASA). AB - Although the psychomotor vigilance task (PVT) is commonly used in sleep and other research settings, normative data for PVT performance in children have not been published. This report presents normal PVT performance measures among children without a sleep disorder participating in the Tucson Children's Assessment of Sleep Apnea (TuCASA) study. TuCASA is a community-based, prospective study of sleep-disordered breathing in Caucasian and Hispanic children ages 6 to 11 years. A standard 10-min PVT trial was completed by 360 participants-48% female and 36% Hispanic; mean age 8.9 years. Detailed analyses were performed for 162 children with respiratory disturbance indices <1 and no parent-reported sleep problems. Mean and median reaction times (RT) decreased with increasing age (p trend < 0.001). Children ages 6 and 11 had median RTs of 544.24 and 325.70 ms, respectively. Standard deviations in RTs also decreased with increasing age (p trend = 0.001), as did lapses (p trend < 0.001), but no trend was apparent in total errors. There were statistically significant (p = 0.006) differences in the performance of boys and girls. Gender differences were greatest at age 6, where boys had shorter RTs, and decreased with age until performance was approximately equal by age 11. No ethnic differences were detected. Children's PVT performance improves with age and differs by gender. These differences should be considered when the PVT is utilized in pediatric populations. PMID- 17333099 TI - Pre-pupation behaviour of the aphid parasitoid Aphidius ervi (Haliday) and its consequences for pre-imaginal learning. AB - Olfactory learning may occur at different stages of insect ontogeny. In parasitoid wasps, it has been mostly shown at adult emergence, whilst it remains controversial at pre-imaginal stages. We followed larval growth of the parasitoid wasp, Aphidius ervi Haliday, inside the host aphid, Acyrthosiphom pisum Harris, and characterised in detail the behaviour of third instar larvae. We found that just before cocoon spinning begins, the third instar larva bites a hole through the ventral side of the mummified aphid exoskeleton. We then evaluated whether this period of exposure to the external environment represented a sensitive stage for olfactory learning. In our first experiment, the third instar larvae were allowed to spin their cocoon on the host plant (Vicia faba L.) surface or on a plastic plate covering the portion of the host plant exposed to the ventral opening. Recently emerged adults of the first group showed a preference for plant volatiles in a glass Y-olfactometer, whereas no preference was found in adults of the second group. In a second experiment, during the period in which the aphid carcass remains open or is being sealed by cocoon spinning, third instar larvae were exposed for 24 h to either vanilla odours or water vapours as control. In this experiment, half of the parasitoid larvae were later excised from the mummy to avoid further exposure to vanilla. Adult parasitoids exposed to vanilla during the larval ventral opening of the mummy showed a significant preference for vanilla odours in the olfactometer, regardless of excision from the mummy. The larval behaviour described and the results of the manipulations performed are discussed as evidences for the acquisition of olfactory memory during the larval stage and its persistence through metamorphosis. PMID- 17333100 TI - Experience, but not distance, influences the recruitment precision in the stingless bee Scaptotrigona mexicana. AB - Recruitment precision, i.e. the proportion of recruits that reach an advertised food source, is a crucial adaptation of social bees to their environment. Studies with honeybees showed that recruitment precision is not a fixed feature, but it may be enhanced by factors like experience and distance. However, little is known regarding the recruitment precision of stingless bees. Hence, in this study, we examined the effects of experience and spatial distance on the precision of the food communication system of the stingless bee Scaptotrigona mexicana. We conducted the experiments by training bees to a three-dimensional artificial patch at several distances from the colony. We recorded the choices of individual recruited foragers, either being newcomers (foragers without experience with the advertised food source) or experienced (foragers that had previously visited the feeder). We found that the average precision of newcomers (95.6 +/- 2.61%) was significantly higher than that of experienced bees (80.2 +/- 1.12%). While this might seem counter-intuitive on first sight, this "loss" of precision can be explained by the tendency of experienced recruits to explore nearby areas to find new rewarding food sources after they had initially learned the exact location of the food source. Increasing the distance from the colony had no significant effect on the precision of the foraging bees. Thus, our data show that experience, but not the distance of the food source, affected the patch precision of S. mexicana foragers. PMID- 17333101 TI - Implantation mechanics of tungsten microneedles into peripheral nerve trunks. AB - 50 microm tungsten microneedles have been used as a means to introduce longitudinal intra-fascicular electrodes (LIFE) into small peripheral nerve fascicles. However, recent attempts to implant LIFEs into larger, human sized nerves with the same needles resulted in buckling failure of the introducer needle. In the present study, the implantation mechanics (penetration forces and penetration dimple depth) of electrosharpened tungsten microneedles ranging in diameters from 50 to 200 microm into freshly excised porcine peripheral nerve trunks between 3 and 5 mm in thickness was characterized to understand the implantation mechanics and to find the minimum needle diameter that would result in successful penetration. The implant success rate was found to be highest with needles having diameters between 80 and 120 microm. The force of successful penetration ranged from 7.2 +/- 0.6 to 71.8 +/- 19.5 mN, and increased monotonically with needle diameter. It also had a tendency to increase with increasing tip angles. The dimple depth for successful penetrations varied between 1 and 1.5 mm, and also tended to increase with increasing tip angles, although it was generally not affected by increased needle diameter. Only the smallest penetration dimple depth was found to be different from the others and was associated with the smallest diameter needle (50 microm). Analysis based on the critical buckling force and the measured implantation forces indicated a 15 mm long needle of 80 microm diameter would be necessary and sufficient to penetrate medium to large sized nerves. PMID- 17333102 TI - An anchored linkage map for sugar beet based on AFLP, SNP and RAPD markers and QTL mapping of a new source of resistance to Beet necrotic yellow vein virus. AB - Rhizomania, caused by Beet necrotic yellow vein virus (BNYVV), is an important sugar-beet disease worldwide and can result in severe losses of root yield and sugar content. We have identified a major QTL for BNYVV resistance from a new source in a segregating population of 158 individuals. The QTL explained an estimated 78% of the observed phenotypic variation and the gene conferring the partial resistance is referred to as Rz4. AFLP was used in combination with bulked segregant analysis (BSA) to develop markers linked to the resistance phenotype. AFLP marker analysis was extended to produce a linkage map that was resolved into nine linkage groups. These were anchored to the nine sugar-beet chromosomes using previously published SNP markers. This represents the first anchored sugar-beet linkage map to be published with non-anonymous markers. The final linkage map comprised 233 markers covering 497.2 cM, with an average interval between markers of 2.1 cM. The Rz4 QTL and an Rz1 RAPD marker were mapped to chromosome III, the known location of the previously identified BNYVV resistance genes Rz1, Rz2 and Rz3. The availability to breeders of new resistance sources such as Rz4 increases the potential for breeding durable disease resistance. PMID- 17333103 TI - Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant? AB - The observation that patients with type 2 diabetes tend to have larger glomeruli than patients with type 1 diabetes was first made more than 10 years ago. It has also been noted that type 2 diabetic patients with nephropathy often have more heterogeneous renal function and structure than type 1 patients. However, whether these observations are linked or have any bearing on the progression of nephropathy in the two types of diabetes remains uncertain. Here we put forward several hypotheses as to why glomerular volume in type 1 differs from that in type 2 diabetes. We suggest that although type 1 and type 2 diabetic patients appear to progress through similar stages of diabetic nephropathy, the route they take may differ. Differences in the way in which the glomeruli respond to the diabetic milieu may enable some type 2 diabetic patients to preserve their filtration surface in the face of an expanding mesangium. PMID- 17333104 TI - Effect of a novel non-thiazolidinedione peroxisome proliferator-activated receptor alpha/gamma agonist on glucose uptake. AB - AIMS/HYPOTHESIS: The effect of the benzopyran derivative T33, a novel non thiazolidinedione agent, was studied on peroxisome proliferator-activated receptors (PPARs), insulin signalling and glucose uptake in adipocytes and skeletal muscle. We hypothesised that T33 could activate PPARgamma and exert a beneficial effect on insulin action on glucose uptake and lipid metabolism. MATERIALS AND METHODS: Using a cell-based reporter gene assay, T33 was identified as a PPARalpha/gamma dual agonist, which activated human PPARgamma and PPARalpha with EC50 values of 19 and 148 nmol/l, respectively. The effect of T33 on glucose metabolism was studied in cultured 3T3-L1 adipocytes and L6 myotubes. In vivo effects of T33 on skeletal muscle were determined in ob/ob mice treated with 8 mg/kg T33. The effect of T33 on metabolic abnormalities was observed in diet induced obese mice. RESULTS: Exposure of 3T3-L1 adipocytes to T33 for 4 days increased basal and insulin-stimulated glucose uptake, with no effect noted in L6 myotubes. Treatment of ob/ob mice for 20 days with T33 normalised basal and insulin-stimulated glucose uptake and increased phosphorylation of Akt and p38 mitogen-activated protein kinase in skeletal muscle. In contrast, phosphorylation of AMP-activated protein kinase was unaltered. Moreover, T33 improved insulin sensitivity and lipid metabolism in diet-induced obese mice. CONCLUSIONS/INTERPRETATION: T33 is non-thiazolidinedione PPARalpha/gamma dual agonist which directly increases basal and insulin-stimulated glucose uptake in adipocytes and secondarily improves insulin action on insulin signalling and glucose metabolism in skeletal muscle from diabetic ob/ob mice. PMID- 17333105 TI - Advanced glycation end products cause increased CCN family and extracellular matrix gene expression in the diabetic rodent retina. AB - AIMS/HYPOTHESIS: Referred to as CCN, the family of growth factors consisting of cystein-rich protein 61 (CYR61, also known as CCN1), connective tissue growth factor (CTGF, also known as CCN2), nephroblastoma overexpressed gene (NOV, also known as CCN3) and WNT1-inducible signalling pathway proteins 1, 2 and 3 (WISP1, 2 and -3; also known as CCN4, -5 and -6) affects cellular growth, differentiation, adhesion and locomotion in wound repair, fibrotic disorders, inflammation and angiogenesis. AGEs formed in the diabetic milieu affect the same processes, leading to diabetic complications including diabetic retinopathy. We hypothesised that pathological effects of AGEs in the diabetic retina are a consequence of AGE-induced alterations in CCN family expression. MATERIALS AND METHODS: CCN gene expression levels were studied at the mRNA and protein level in retinas of control and diabetic rats using real-time quantitative PCR, western blotting and immunohistochemistry at 6 and 12 weeks of streptozotocin-induced diabetes in the presence or absence of aminoguanidine, an AGE inhibitor. In addition, C57BL/6 mice were repeatedly injected with exogenously formed AGE to establish whether AGE modulate retinal CCN growth factors in vivo. RESULTS: After 6 weeks of diabetes, Cyr61 expression levels were increased more than threefold. At 12 weeks of diabetes, Ctgf expression levels were increased twofold. Treatment with aminoguanidine inhibited Cyr61 and Ctgf expression in diabetic rats, with reductions of 31 and 36%, respectively, compared with untreated animals. Western blotting showed a twofold increase in CTGF production, which was prevented by aminoguanidine treatment. In mice infused with exogenous AGE, Cyr61 expression increased fourfold and Ctgf expression increased twofold in the retina. CONCLUSIONS/INTERPRETATION: CTGF and CYR61 are downstream effectors of AGE in the diabetic retina, implicating them as possible targets for future intervention strategies against the development of diabetic retinopathy. PMID- 17333106 TI - Estimated glomerular filtration rate, albuminuria and mortality in type 2 diabetes: the Casale Monferrato study. AB - AIMS/HYPOTHESIS: Estimated glomerular filtration rate (eGFR) predicts mortality in non-diabetic populations, but its role in people with type 2 diabetes is unknown. We assessed to what extent a reduction in eGFR in people with type 2 diabetes predicts 11-year all-cause and cardiovascular mortality, independently of AER and other cardiovascular risk factors. MATERIALS AND METHODS: The study population was the population-based cohort (n = 1,538; median age 68.9 years) of the Casale Monferrato Study. GFR was estimated by the abbreviated Modification of Diet in Renal Disease Study equation. RESULTS: At baseline, the prevalence of chronic kidney disease (eGFR <60 ml min(-1) 1.73 m(-2)) was 34.3% (95% CI 33.0 36.8). There were 670 deaths in 10,708 person-years of observation. Hazard ratios of 1.23 (95% CI 1.03-1.47) for all-cause mortality and 1.18 (95% CI 0.92-1.52) for cardiovascular mortality were observed after adjusting for cardiovascular risk factors and AER. When five levels of eGFR were analysed we found that most risk was conferred by eGFR 15-29 ml min(-1) 1.73 m(-2), whereas no increased risk was evident in people with eGFR values between 30 and 59 ml min(-1) 1.73 m(-2). In an analysis stratified by AER categories, a significant increasing trend in risk with decreasing eGFR was evident only in people with macroalbuminuria. CONCLUSIONS/INTERPRETATION: Our study suggests that in type 2 diabetes macroalbuminuria is the main predictor of mortality, independently of both eGFR and cardiovascular risk factors, whereas eGFR provides no further information in normoalbuminuric people. PMID- 17333107 TI - School performance in children with type 1 diabetes--a population-based register study. AB - AIMS/HYPOTHESIS: We examined the school marks of diabetic children in Sweden at the time of leaving compulsory education. Marks were examined in comparison with non-diabetic children and with special regard to age at onset of diabetes. SUBJECTS AND METHODS: The study involved 5,159 children who developed diabetes between 1 July 1977 and 1 July 2000, and 1,330,968 non-diabetic children. We linked the nationwide Swedish Childhood Diabetes Register to the Swedish School Mark Register, which contains school marks for all children in Sweden at the time of leaving compulsory education (usually at 16 years old). Adjustment was made for potential confounders such as year of birth, maternal age, parity and educational level. RESULTS: The mean of all numerical school marks for diabetic children was slightly but statistically significantly lower than those of the referent children (3.15 +/- 0.01 [mean + SD] vs 3.23, p < 0.001). The lowest mean score was among children with diabetes diagnosis before the age of 2 years (2.97 +/- 0.09 vs 3.08-3.17 in the older age groups, p = 0.10). When individual subjects were studied (sports, mathematics, English and Swedish), a more complex picture emerged. In four subjects (mathematics, English, Swedish and sports) the risk of a diabetic child not getting a school mark or not passing was increased; in sports and English the diabetic children had significantly reduced odds of getting a high mark. CONCLUSIONS/INTERPRETATION: Despite a well-developed diabetes care system, we have not succeeded in preventing the disease from affecting school achievements. Among children with a young age at onset and therefore longer duration, the negative effects tend to be greater. PMID- 17333108 TI - The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes. AB - AIMS/HYPOTHESIS: Genetic factors may account for familial clustering related to diabetes complications. Studies have shown a significant relationship between the presence of the deletion (D) allele of the gene encoding ACE and risk of severe hypoglycaemia. This large prospective cohort study assesses this relationship in a large sample of children and adolescents with type 1 diabetes. SUBJECTS AND METHODS: We studied 585 children and adolescents (mean age 11.9 +/- 4 years, 48.4% males). The frequency of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was prospectively assessed over the 13-year period 1992 2004. Patients were seen with their parents every 3 months and data recorded at each visit. The ACE gene was detected using PCR. RESULTS: In our cohort of 585 children, 186 (31.8%) had at least one episode of severe hypoglycaemia, and of these 28.0% had the II genotype, 48.9% had the ID genotype and 23.1% had the DD genotype. This was in agreement with the Hardy-Weinberg proportion. A total of 477 severe hypoglycaemic episodes was recorded with a total of 3,404 person-years of follow-up, giving a total incidence of 14 per 100 patient-years. No significant increase in risk for DD genotype (incidence rate ratio = 0.97, 95% CI 0.61-1.55) relative to II genotype was observed. CONCLUSIONS/INTERPRETATION: This large prospective study concludes that the presence of the D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia in type 1 diabetic children and adolescents. PMID- 17333109 TI - Improved survival rate in patients with diabetes and end-stage renal disease in Denmark. AB - AIMS/HYPOTHESIS: We investigated the survival rate of Danish diabetic patients with end-stage renal disease (ESRD) between 1990 and 2005 and evaluated possible predictors of survival rate. MATERIALS AND METHODS: Data were obtained from the Danish National Register on Dialysis and Transplantation and from the Scandiatransplant database. Survival rates in different patient groups and association with age, sex, calendar time, waiting-list status and renal transplantation were evaluated using a multivariate Cox regression model. RESULTS: During the study period 8,421 patients (13% type 1 diabetic, 9% type 2 diabetic and 78% non-diabetic) started renal replacement therapy. The overall survival rate improved by 15% per five calendar years (hazard ratio [HR]=0.85, 95% CI: 0.81-0.88). The percentage of patients within each group who received renal transplantation was: type 1 diabetic: 26%, type 2 diabetic: 5%, non diabetic: 24%. The survival rate of transplanted patients with diabetes mellitus (types 1 and 2) compared with non-diabetic patients at 1 year was: 95 vs 93%, at 5 years: 80 vs 85% and at 10 years: 52 vs 71%. Among diabetic patients survival rate was better in transplanted than in waiting-list patients (HR = 0.21, 95% CI 0.13-0.34), whereas the survival rate in waiting-list patients seemed to be superior to the survival rate among non-transplantation candidates (HR = 0.75, 95% CI 0.53-0.1.02, p = 0.07). CONCLUSIONS/INTERPRETATION: The survival rate of diabetic patients with ESRD has improved during the last 15 years. Although some selection bias may exist, significantly improved survival rate was observed among transplanted patients compared with dialysis patients on the waiting-list for transplantation. Renal transplantation should therefore be offered to diabetic patients with ESRD whenever possible. PMID- 17333110 TI - Protein tyrosine phosphatase 1B is not a major susceptibility gene for type 2 diabetes mellitus or obesity among Pima Indians. AB - AIM/HYPOTHESIS: Single-nucleotide polymorphisms (SNPs) in the protein tyrosine phosphatase 1B gene (PTPN1) have been reported to be associated with type 2 diabetes in white subjects, and insulin sensitivity and fasting glucose levels in Hispanic Americans. In this study, we determined whether SNPs in PTPN1 also have a role in type 2 diabetes susceptibility in Pima Indians, a population with the world's highest reported prevalence and incidence rates of this disease. MATERIALS AND METHODS: Thirty-one SNPs across a 161-kb region encompassing PTPN1 were genotyped in 1,037 Pima Indians for association studies with type 2 diabetes and obesity. RESULTS: Twenty-five of the SNPs had allele frequencies >0.05, and these SNPs fell into two linkage disequilibrium blocks (D' > 0.9). Block 1 contains six SNPs that span a 61-kb region upstream of PTPN1, while block 2 contains 19 SNPs that cover the entire PTPN1 gene. None of the SNPs, analysed individually or as haplotypes, was associated with either type 2 diabetes or obesity. However, three SNPs located in block 1 were nominally associated (p values ranging from 0.01 to 0.05) with insulin sensitivity as measured by the hyperinsulinaemic-euglycaemic clamp technique. CONCLUSIONS/INTERPRETATION: Based on our association results, we conclude that SNPs within PTPN1 are unlikely to have a major role in the aetiology of type 2 diabetes or obesity in Pima Indians. PMID- 17333111 TI - Global profiling of genes modified by endoplasmic reticulum stress in pancreatic beta cells reveals the early degradation of insulin mRNAs. AB - AIMS/HYPOTHESIS: Pancreatic beta cells respond to endoplasmic reticulum (ER) stress by activating the unfolded protein response. If the stress is prolonged, or the adaptive response fails, apoptosis is triggered. We used a 'homemade' microarray specifically designed for the study of beta cell apoptosis (the APOCHIP) to uncover mechanisms regulating beta cell responses to ER stress. MATERIALS AND METHODS: A time course viability and microarray analysis was performed in insulin-producing INS-1E cells exposed to the reversible ER stress inducer cyclopiazonic acid (CPA). Modification of selected genes was confirmed by real-time RT-PCR, and the observed inhibition of expression of the insulin-1 (Ins1) and insulin-2 (Ins2) genes was further characterised in primary beta cells exposed to a diverse range of agents that induce ER stress. RESULTS: CPA-induced ER stress modified the expression of 183 genes at one or more of the time points studied. The expression of most of these genes returned to control levels after a 3 h recovery period following CPA removal, with all cells surviving. Two groups of genes were particularly affected by CPA, namely, those related to cellular responses to ER stress, which were mostly upregulated, and those related to differentiated beta cell functions, which were downregulated. Levels of Ins1 and Ins2 mRNAs were severely decreased in response to CPA treatment as a result of degradation, and there was a concomitant increase in the level of IRE1 activation. CONCLUSIONS/INTERPRETATION: In this study we provide the first global analysis of beta cell molecular responses to a severe ER stress, and identify the early degradation of mRNA transcripts of the insulin genes as an important component of this response. PMID- 17333112 TI - Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study. AB - AIMS/HYPOTHESIS: The aim of this study was to examine the association between baseline body iron stores and new-onset diabetes. SUBJECTS AND METHODS: We studied the association between baseline serum ferritin concentration and type 2 diabetes in 360 clinically incident diabetes cases and 758 controls nested within the EPIC (European Prospective Investigation of Cancer)-Norfolk Cohort Study. Serum ferritin levels were categorised into five groups: sex-specific quartiles of the normal range of ferritin and a group with clinically raised ferritin below levels indicative of haemochromatosis. RESULTS: Baseline serum ferritin was higher among cases than control participants (geometric mean: men 96.6 vs 67.8 ng/ml, respectively, p < 0.001; women 45.9 vs 34.8 ng/ml, respectively, p = 0.005). In analyses adjusted for known risk factors (age, BMI, sex, family history, physical activity, smoking habit) and dietary factors measured by 7-day food diary, the risk of diabetes was markedly elevated in participants with clinically raised ferritin compared with the lowest quartile (odds ratio [OR] 7.4, 95% CI 3.5-15.4). Further adjustment for potential confounding by inflammation (C-reactive protein, IL-6 and fibrinogen) had no material impact on the observed association, while adjustment for hepatic enzymes (alanine aminotransferase and gamma glutamyl transferase) and adiponectin attenuated the magnitude of association, but it remained statistically significant (OR 3.2 [1.3 7.6]). CONCLUSIONS/INTERPRETATION: Serum ferritin is an important and independent predictor of the development of diabetes. This finding may have important implications for understanding the aetiology of diabetes. PMID- 17333113 TI - Focal adhesion kinase regulates insulin resistance in skeletal muscle. AB - AIMS/HYPOTHESIS: On the basis of our previous studies, we investigated the possible role of focal adhesion kinase (FAK) in the development of insulin resistance in skeletal muscle, a major organ responsible for insulin-stimulated glucose uptake. MATERIALS AND METHODS: Insulin-resistant C2C12 skeletal muscle cells were transfected with FAK wild-type or FAK mutant plasmids, knocked down using small interfering RNA (siRNA), and their effects on the levels and activities of insulin-signalling molecules and on glucose uptake were determined. RESULTS: A significant decrease in tyrosine phosphorylation of FAK in insulin resistant C2C12 cells was observed. A similar decrease was observed in skeletal muscle obtained from insulin-resistant Sprague-Dawley rats fed a high-fat diet. Increased levels of FAK in insulin-resistant C2C12 skeletal muscle cells increased insulin sensitivity and glucose uptake. These effects were reversed by an increase in the level of kinase activity mutant FAK or suppression of endogenous FAK by siRNA. FAK was also found to interact downstream with insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase C and glycogen synthase kinase 3beta, leading to translocation of glucose transporter 4 and resulting in the regulation of glucose uptake. CONCLUSIONS/INTERPRETATION: The present study provides strong evidence that the modulation of FAK level regulates the insulin sensitivity of skeletal muscle cells. The results demonstrate a direct role of FAK in insulin-resistant skeletal muscle cells for the first time. PMID- 17333114 TI - Alveolar edema dispersion and alveolar protein permeability during high volume ventilation: effect of positive end-expiratory pressure. AB - OBJECTIVES: To evaluate whether PEEP affects intrapulmonary alveolar edema liquid movement and alveolar permeability to proteins during high volume ventilation. DESIGN AND SETTING: Experimental study in an animal research laboratory. SUBJECTS: 46 male Wistar rats. INTERVENTIONS: A (99m)Tc-labeled albumin solution was instilled in a distal airway to produce a zone of alveolar flooding. Conventional ventilation (CV) was applied for 30 min followed by various ventilation strategies for 3 h: CV, spontaneous breathing, and high volume ventilation with different PEEP levels (0, 6, and 8 cmH(2)O) and different tidal volumes. Dispersion of the instilled liquid and systemic leakage of (99m)Tc albumin from the lungs were studied by scintigraphy. MEASUREMENTS AND RESULTS: The instillation protocol produced a zone of alveolar flooding that stayed localized during CV or spontaneous breathing. High volume ventilation dispersed alveolar liquid in the lungs. This dispersion was prevented by PEEP even when tidal volume was the same and thus end-inspiratory pressure higher. High volume ventilation resulted in the leakage of instilled (99m)Tc-albumin from the lungs. This increase in alveolar albumin permeability was reduced by PEEP. Albumin permeability was more affected by the amplitude of tidal excursions than by overall lung distension. CONCLUSIONS: PEEP prevents the dispersion of alveolar edema liquid in the lungs and lessens the increase in alveolar albumin permeability due to high volume ventilation. PMID- 17333116 TI - Comment on "Attitudes of European physicians, nurses, patients, and families regarding end-of-life decisions: the ETHICATT study" by Sprung et al. PMID- 17333117 TI - Adult congenital heart disease: intensive care management and outcome prediction. AB - OBJECTIVE: Improved patient survival and increasingly complex surgery have expanded the requirement for specialist care for patients with adult congenital heart disease (ACHD). Despite the recent publications of management guidelines for ACHD, data concerning optimal patterns of care in the peri-operative/critical care period of this challenging population are sparse. The aims of the current study were to therefore to determine the pattern of intensive care unit (ICU) management, resource utilisation and predictors of mortality in critically ill ACHD patients. DESIGN, SETTING AND PATIENTS: Data were collected prospectively for patients with ACHD stratified for complexity of disease admitted to the ICU of a tertiary cardiothoracic centre (1997-2002). Multivariate analysis of pre operative indices as predictors of mortality was performed. Of 342 ACHD admissions (total mortality 4.4%, simple 0%, moderate/complex 10.6%), the requirement for specialist investigations and interventions was high, reflected in ICU admission costs per patient (simple $5391+/-130, moderate $13218+/-261, complex $30074+/-689). Standard severity of illness scoring systems did not accurately predict mortality; however, abnormal pre-operative thyroid function (p=0.0048), creatinine (p=0.0032) and bilirubin (p=0.0021) were highly predictive of mortality. CONCLUSIONS: Peri-operative mortality in patients with ACHD is low overall but varies with disease complexity. Such patients have a high requirement for specialist ICU investigation/intervention. Although standard severity of illness scoring is unhelpful, simple pre-operative parameters may predict peri operative mortality. These findings reflect the requirement for specialist care, and have implications for planning service provision, training and operative consent in ACHD patients. PMID- 17333118 TI - Elimination of daily routine chest radiographs in a mixed medical-surgical intensive care unit. AB - OBJECTIVE: To determine the impact of elimination of daily routine chest radiographs (CXRs) in a mixed medical-surgical intensive care unit (ICU) on utility of on demand CXRs, length of stay (LOS) in ICU, readmission rate, and mortality rate. DESIGN AND SETTING: Prospective, nonrandomized, controlled study in a 28-bed ICU. Analysis included data of all admitted ICU patients during 5 months before and after elimination of daily routine CXRs. RESULTS: Before elimination, 2457 daily routine CXRs and 1437 on demand CXRs were obtained from 754 patients. After elimination, 1267 CXRs were obtained from 622 patients. The ratio of CXRs/patient day decreased from 1.1+/-0.3 to 0.6+/-0.4 (p<0.05). Elimination did not result in a change in utility and timing of on demand CXRs. The absolute diagnostic and therapeutic value of on demand CXRs increased with elimination of daily routine CXRs: before intervention, 147 unexpected predefined abnormalities were found (10.2% of all on demand CXRs in 15.9% of all patients), of which 57 (3.9%) in 6.4% of all patients led to a change in therapy. After intervention, 156 unexpected predefined abnormalities were found (11.6%; p<0.05), of which 61 (4.8%) in 9.5% of all patients (p<0.05) led to a change in therapy. The LOS in ICU, readmission rate and ICU, and hospital mortality rate were not influenced by the change in strategy. CONCLUSIONS: Elimination of daily routine CXRs reduced the number of CXRs in a mixed medical-surgical ICU, while not affecting readmission rate and ICU and hospital mortality rates. PMID- 17333120 TI - Effects of pulsed electromagnetic fields on patients' recovery after arthroscopic surgery: prospective, randomized and double-blind study. AB - Severe joint inflammation following trauma, arthroscopic surgery or infection can damage articular cartilage, thus every effort should be made to protect cartilage from the catabolic effects of pro-inflammatory cytokines and stimulate cartilage anabolic activities. Previous pre-clinical studies have shown that pulsed electromagnetic fields (PEMFs) can protect articular cartilage from the catabolic effects of pro-inflammatory cytokines, and prevent its degeneration, finally resulting in chondroprotection. These findings provide the rational to support the study of the effect of PEMFs in humans after arthroscopic surgery. The purpose of this pilot, randomized, prospective and double-blind study was to evaluate the effects of PEMFs in patients undergoing arthroscopic treatment of knee cartilage. Patients with knee pain were recruited and treated by arthroscopy with chondroabrasion and/or perforations and/or radiofrequencies. They were randomized into two groups: a control group (magnetic field at 0.05 mT) and an active group (magnetic field of 1.5 mT). All patients were instructed to use PEMFs for 90 days, 6 h per day. The patients were evaluated by the Knee injury and Osteoarthritis Outcome Score (KOOS) test before arthroscopy, and after 45 and 90 days. The use of non-steroidal anti-inflammatory drugs (NSAIDs) to control pain was also recorded. Patients were interviewed for the long-term outcome 3 years after arthroscopic surgery. Thirty-one patients completed the treatment. KOOS values at 45 and 90 days were higher in the active group and the difference was significant at 90 days (P < 0.05). The percentage of patients who used NSAIDs was 26% in the active group and 75% in the control group (P = 0.015). At 3 years follow-up, the number of patients who completely recovered was higher in the active group compared to the control group (P < 0.05). Treatment with I-ONE aided patient recovery after arthroscopic surgery, reduced the use of NSAIDs, and also had a positive long-term effect. PMID- 17333119 TI - Effects of open endotracheal suction on lung volume in infants receiving HFOV. AB - OBJECTIVE: To describe the pattern and magnitude of lung volume change during open endotracheal tube (ETT) suction in infants receiving high-frequency oscillatory ventilation (HFOV). DESIGN: Prospective observational clinical study. SETTING: Tertiary neonatal intensive care unit. PATIENTS AND PARTICIPANTS: Seven intubated and muscle-relaxed newborn infants receiving HFOV. INTERVENTIONS: Open ETT suction was performed for 6 s at -100 mmHg using a 6-F catheter passed to the ETT tip after disconnection from HFOV. The HFOV was then recommenced at the same settings as prior to ETT suction. MEASUREMENTS AND RESULTS: Change in lung volume (DeltaV (L)) referenced to baseline lung volume before suction was measured with a calibrated respiratory inductive plethysmography recording from 30 s before until 60 s after ETT suction. In all infants ETT suction resulted in significant loss of lung volume. The mean DeltaV (L) during suctioning was -13 ml/kg (SD 4 ml/kg) (p<0.0001 vs. baseline, repeated-measures ANOVA), with a mean 76.5% (SD 14.1%) of this volume loss being related to circuit disconnection. After recommencing HFOV lung volume was rapidly regained with mean DeltaV (L) at 60 s being 1 ml/kg (SD 4 ml/kg) below baseline (p>0.05, Tukey post-test). CONCLUSIONS: Open ETT suction caused a significant but transient loss of lung volume in muscle relaxed newborn infants receiving HFOV. PMID- 17333121 TI - Synovial chondromatosis of the posterior cruciate ligament managed by a posterior posterior triangulation technique. AB - Various causes have been reported for cystic lesions arising from the cruciate ligaments. We present a case of synovial chondromatosis that involved the posterior cruciate ligament and was treated by an arthroscopic posterior posterior triangulation method. We recommend that synovial chondromatosis be considered in the differential diagnosis of cystic lesions of the cruciate ligaments. Lesions involving the posterior aspect of the posterior cruciate ligament, as in the presented case, can be accessed via the standard anterior arthroscopic portals. However, scattered synovial chondromatosis masses located in the posterolateral compartment are difficult to access via anterior portals. We suggest that the arthroscopic posterior-posterior triangulation technique may be useful for the management of such cases. PMID- 17333122 TI - Idiopathic adhesive capsulitis of the shoulder: a review. AB - Many terms have been used to describe what has been called idiopathic adhesive capsulitis of the shoulder. This pathology is defined as a self-limiting condition of unknown etiology. The natural history is 18-30 months even though a high-percentage of patient present impaired range of movement even at long-term follow-up. The diagnosis is mainly clinical and no significant changes are normally present at MRI or CT scan. Several treatment options have been tried over the years with different approaches and results. PMID- 17333123 TI - Comparison of conservative treatment with and without manual physical therapy for patients with shoulder impingement syndrome: a prospective, randomized clinical trial. AB - The aim of this prospective, randomized clinical study was to compare the effectiveness of two physical therapy treatment approaches for impingement syndrome, either by joint and soft tissue mobilization techniques or by a self training program. Thirty patients (Group 1, n = 15; Group 2, n = 15) with the diagnosis of an outlet impingement syndrome of the shoulder were treated either by strengthening the depressors of the humeral head with a guided self-training program (Group 1, age 49.5 +/- 7.9 years), or by joint and soft tissue mobilization techniques (Group 2, age 48.1 +/- 7.5 years). Group 1 was instructed with the active range of motion (ROM), stretching and strengthening exercise program including rotator cuff muscles, rhomboids, levator scapulae and serratus anterior with an elastic band at home at least seven times a week for 10-15 min and Group 2 received a prescription for 12 sessions of joint and soft tissue mobilization techniques, ice application, stretching and strengthening exercise programs and patient education in clinic for three times per week. All patients were tested with visual analog scale (VAS) for pain level, goniometric measurement for ROM and algometry for the pain threshold. Function was measured with a functional assessment questionnaire. The VAS (10 cm) used to measure pain with functional activities and the functional assessment questionnaire (Neer) were also measured 3 months after the initiation of treatment. Subjects in both groups experienced significant decreases in pain and increases in shoulder function, but there was significantly more improvement in the manual therapy group compared to the exercise group. For example, pain in the manual therapy group was reduced from a pre-treatment mean (+/-SD) of 6.7 (+/-0.3) to a post treatment mean of 2.0 (+/-2.0). In contrast, pain in the exercise group was reduced from a pre-treatment mean of 6.6 (+/-1.4) to a post-treatment mean of 3.0 (+/-1.8). ROM at flexion, abduction and external rotation in the manual therapy group improved significantly while ROM in the exercise group did not. There were statistically differences among the groups in function (P > 0.05). Group 2 showed significantly greater improvements in the Neer Questionnaire score and shoulder satisfaction score than Group 1. The patients treated with manual physical therapy applied by experienced physical therapists combined with supervised exercise in a brief clinical trial showed improvement of symptoms including increasing strength, decreasing pain and improving function earlier than with exercise program. PMID- 17333125 TI - Icons, do we need them? PMID- 17333124 TI - Meniscus allograft transplantation: a current concepts review. AB - Meniscus allotransplantation represents the biological solution for the symptomatic, meniscus-deficient patient who has not developed advanced osteoarthritis. A growing body of evidence suggests that pain relief and functional improvement may reliably be achieved at short- and medium-term follow up, and even, in some cases, at long-term (>10 years) follow-up. Future research must address the issue of optimal timing of the procedure and whether meniscal transplantation results in demonstrable long-term benefits, especially with regard to protection of articular cartilage. PMID- 17333126 TI - Diversity of Microcystis aeruginosa isolates (Chroococcales, Cyanobacteria) from East-African water bodies. AB - With exception of South Africa, very little is known about the presence and abundance of toxic cyanobacteria and cyanobacterial blooms on the African continent. The close proximity between society and nature, and the use of the sparse water resources as drinking water in large parts of Africa, lead to the recognition that more knowledge on toxic cyanobacterial blooms is of major importance. The bloom forming cyanobacterium Microcystis aeruginosa is known to produce cyclic heptatoxins (microcystins) which can be toxic to humans. In this study the morphological, genetic, and chemical characters of 24 strains of M. aeruginosa from several water bodies in Kenya and Uganda, some of them used as drinking water sources, were examined. The M. aeruginosa strains possessed different levels of diversity depending on characterisation method. Four morphotypes were identified based on the traditional morphological approach, 10 genotypes by DNA sequence comparison of the PC-IGS and ITS1 rDNA regions, and 10 chemotypes based on MALDI-TOF-MS oligopeptide analysis. Only 4 of the 24 isolated strains from East Africa were found to produce microcystins, while oligopeptides belonging to the aeruginosin and cyanopeptolin class were detected in most strains. PMID- 17333127 TI - Exposure of C6 glioma cells to Pb(II) increases the phosphorylation of p38(MAPK) and JNK1/2 but not of ERK1/2. AB - Pb(II) is a neurotoxic pollutant that produces permanent cognitive deficits in children. Pb(II) can modulate cell signaling pathways and cell viability in a variety of cell types. However, these actions are not well demonstrated on glial cells, which represent an important target for metals into the central nervous system. The present work was undertaken to determine the ability of Pb(II) in modulating the activity of mitogen activated protein kinases (MAPKs) in cultures of C6 rat glioma cells, a useful functional model for the study of astrocytes. Additionally, cell viability was analyzed by measurement of MTT reduction. Cells were exposed to lead acetate 0.1, 1, 10 microM for 24 and 48 h. MAPKs activation in particular ERK1/2, p38(MAPK) and JNK1/2 - were analyzed by western blotting. Results showed that 10 microM Pb(II) treatment for 24 h caused a discrete stimulation of p38(MAPK) phosphorylation. However, 1 and 10 microM Pb(II) treatment for 48 h provoked a significant stimulation in the phosphorylation state of p38(MAPK) and JNK1/2. The phosphorylation state of ERK1/2 was not modified by any Pb(II) treatment. Moreover, data indicate that at 48 h treatment even 1 microM Pb(II) can be cytotoxic, causing impairment on cell viability. Therefore, depending on a long incubation period, a significant concomitant activation of p38(MAPK) and JNK1/2 by Pb(II) took place in parallel with the impairment of C6 glioma cells viability. PMID- 17333128 TI - Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats. AB - Inhibition of the renin angiotensin aldosterone system (RAAS) produces protective effects on cardio-renal injury in type 2 diabetes. Vasopeptidase inhibitors (VPI) represent a new pharmacological tool, acting by simultaneous inhibition of the RAAS and neutral endopeptidase. We examined the effects of chronic VPI on renal function and morphology in experimental type 2 diabetes as compared to angiotensin converting enzyme inhibition (ACE-I). Zucker diabetic fatty rats aged 13 weeks were treated with either VPI (AVE7688, ZDF-VPI, n = 8) or ACE-I (Ramipril, ZDF-ACE-I, n = 7) or placebo (ZDF, n = 8). Heterozygous rats served as non-diabetic controls (Ctr, n = 8). Both treatments led to a similar decrease in blood pressure. After 10 weeks of treatment, ZDF developed marked albuminuria. The latter was significantly attenuated in ZDF-VPI as compared to ZDF and ZDF-ACE I. Renal histology revealed a significant expansion in the glomerular tuft area in all ZDF groups. However, expression of glomerular desmin, which has been recognized as a sensitive marker of early podocyte damage, was significantly increased in ZDF as compared to Ctr. Desmin was reduced in ZDF-VPI but not in animals treated with ACE-I. There was a correlation between albumin excretion and desmin-positive glomerular area. In experimental type 2 diabetes, albuminuria correlates to podocyte damage. These hallmarks of diabetic nephropathy are attenuated by VPI to a greater extent than by ACE-I alone. These findings suggest that podocyte damage is an early critical step in the progression of diabetic nephropathy, and that VPI is a promising pharmacological tool in the treatment of diabetic renal disease. PMID- 17333129 TI - Isobolographic analysis of interaction between drugs with nonparallel dose response relationship curves: a practical application. AB - The objective of this study was to characterize the anticonvulsant and acute adverse-effect potentials of topiramate (TPM) and gabapentin (GBP)-two second generation antiepileptic drugs administered alone and in combination in the maximal electroshock (MES)-induced seizures and chimney test in mice. The anticonvulsant and acute adverse effects of the combination of TPM with GBP at the fixed ratio of 1:1 were determined using the type I isobolographic analysis for nonparallel dose-response relationship curves (DRRCs). To ascertain any pharmacokinetic contribution to the observed interaction between TPM and GBP, total brain concentrations of both drugs were determined. The isobolographic analysis of interaction for TPM and GBP, whose DRRCs were not parallel in both MES and chimney tests, was accompanied with a presentation of all required calculations allowing the determination of lower and upper lines of additivity. The isobolographic analysis revealed that TPM combined with GBP at the fixed ratio combination of 1:1 interacted supraadditively (synergistically) in terms of suppression of MES-induced seizures, and simultaneously, the combination produced additive interaction with respect to motor coordination impairment (adverse effects) in the chimney test. The evaluation of pharmacokinetic characteristics of interaction for the combination of TPM with GBP revealed that neither TPM nor GBP affected their total brain concentrations in experimental animals, and thus, the observed interaction in the MES test was pharmacodynamic in nature. In conclusion, the combination of TPM with GBP, because of supraadditivity in the MES test and additivity in terms of motor coordination impairment in the chimney test as well as lack of pharmacokinetic interactions between drugs, fulfilled the criterion of a favorable combination, worthy of recommendation in further clinical practice. PMID- 17333130 TI - Pentylenetetrazol-kindling in mice overexpressing heat shock protein 70. AB - Kindling induced by the convulsant pentylenetetrazol (PTZ) is an accepted model of primary generalized epilepsy. Because seizures represent a strong distressing stimulus, stress-induced proteins such as heat shock proteins might counteract the pathology of increased neuronal excitation. Therefore, the aim of the present study was to determine whether PTZ kindling outcome parameters are influenced by heat shock protein 70 (Hsp70) overexpression in Hsp70 transgenic mice as compared to the respective wild-type mice. Kindling was performed by nine intraperitoneal injections of PTZ (ED(16) for induction of clonic-tonic seizures, every 48 h); control animals received saline instead of PTZ. Seven days after the final injection, all mice received a PTZ challenge dose. Outcome parameters included evaluation of seizure stages and overall survival rates. In addition, histopathological findings such as cell number in hippocampal subfields CA1 and CA3 were determined. The onset of the highest convulsion stage was delayed in Hsp70 transgenic mice as compared to wild-type mice, and overall survival during kindling was improved in Hsp70 transgenic mice as compared to wild-type mice. In addition, a challenge dose after termination of kindling produced less severe seizures in Hsp70 transgenic mice than in wild-type mice. PTZ kindling did not result in significant subsequent neuronal cell loss in CA1 or CA3 neither in wild type mice nor in the Hsp70 transgenic mice. The results of the present experiments clearly demonstrate that overexpression of Hsp70 exerts protective effects regarding seizure severity and overall survival during PTZ kindling. In addition, the decreased seizure severity in Hsp70 transgenic mice after a challenge dose suggests an interference of Hsp70 with the developmental component of kindling. PMID- 17333131 TI - Efficacy and safety of risperidone in the treatment of elderly patients suffering from organic brain disease (organic brain syndrome): results from a double-blind, randomized, placebo-controlled clinical trial. PMID- 17333132 TI - Nicotine increases FosB expression within a subset of reward- and memory-related brain regions during both peri- and post-adolescence. AB - INTRODUCTION: Periadolescent nicotine exposure is associated with increased consumption and rewarding properties of abused drugs. In the case of peri- but not post-adolescent animals, these effects are persistent and last to adulthood, suggesting that early nicotine treatment may alter postnatal CNS development in ways that contribute to long-term problems with drug abuse. MATERIALS AND METHODS: To begin to identify brain regions that may be altered by developmental nicotine exposure, we have measured expression of a transcription factor, FosB, within a series of reward- and memory-related brain regions of Sprague-Dawley rats. RESULTS: FosB expression is known to acutely and cumulatively increase within a subset of brain regions, particularly nucleus accumbens, after exposure to many classes of abused drugs. Our results demonstrate that FosB is increased within nucleus accumbens and also the granule cell layer of hippocampal dentate gyrus after both peri- and post-adolescent nicotine exposure (0.4 mg kg(-1) day( 1) from days 34 to 43 and 60 to 69, respectively). In periadolescents, expression increases were detected 2 days after nicotine exposure, and persisted for weeks, through at least early adulthood at 80 days of age. In post-adolescents, expression increases persisted for at least 11 days to postnatal day 80. DISCUSSION: These findings demonstrate that nicotine treatment during both peri- and post-adolescence persistently alters activity of brain regions involved in reward and memory. CONCLUSION: Because this altered gene expression occurs after both peri- and post-adolescent treatment, it cannot be directly responsible for increased consumption and rewarding properties of abused drugs previously established to be distinctly associated with periadolescent nicotine exposure. PMID- 17333134 TI - Stereotyped and complex motor routines expressed during cocaine self administration: results from a 24-h binge of unlimited cocaine access in rats. AB - RATIONALE: Cocaine binges represent the most severe form of cocaine taking due to high levels of cocaine consumed and a potential loss of self-control over cocaine taking. Experimentally, regulation of intravenous cocaine self-administration is observed during binges as revealed by nearly constant sequential inter-infusion intervals, suggesting that pharmacological and unconditioned behavioral effects of cumulative cocaine leave intact its reinforcing effect. OBJECTIVE: To elucidate factors that contribute to the patterning of cocaine self administration behavior during binges, the current study quantifies the expression of specific motor routines that emerge from the beginning of a cocaine infusion until the next cocaine reinforcement is received, in six separate rats over 24 h of continuous access. MATERIALS AND METHODS: During each 24-h cocaine binge, behavior was continuously monitored using a force plate actometer that provides reliable quantitation of rodent behaviors, including rotational behavior, locomotor activity, and focused stereotypy. RESULTS: Corroborating earlier results, each rat accumulated between 4 and 11 mg/kg/h during periods of active cocaine self-administration. All rats displayed a similar narrow range of unconditioned behavioral responses to cocaine, yet each rat varied with regard to the intensity and specific predominant pattern of behavioral activation. Focused stereotyped behavior, in particular, was apparent in all rats and continued for as long as cocaine self-administration behavior remained active. CONCLUSIONS: The current results support the hypothesis that individual differences in cocaine's pharmacodynamics may contribute to specific behaviors expressed during cocaine self-administration, but leave unresolved whether or not intense unconditioned behavior (e.g., focused stereotypy) conflicts with, or contributes to, ongoing self-administration behavior. PMID- 17333133 TI - Tolerance to the effect of 2,5-dimethoxy-4-iodoamphetamine (DOI) on free-operant timing behaviour: interaction between behavioural and pharmacological mechanisms. AB - RATIONALE: The psychostimulant d-amphetamine, the D(2/3) dopamine receptor agonist quinpirole and the 5-HT(2) receptor agonist 2,5-dimethoxy-4 iodoamphetamine (DOI) have similar effects on free-operant timing behaviour. There is evidence that tolerance develops to the effects of psychostimulants on timing performance during chronic treatment; this tolerance is generally attributed to behavioural adaptation rather than to pharmacological desensitisation. There have been no previous investigations of tolerance to the effect of DOI on free-operant timing behaviour. OBJECTIVE: To demonstrate tolerance to DOI's effect on timing performance and to examine the nature of this tolerance. MATERIALS AND METHODS: Rats were trained under the free-operant psychophysical procedure to press two levers (A and B) in 80-s trials in which reinforcement was provided intermittently for responding on A in the first half and B in the second half of the trial. Percent responding on B (%B) was recorded in successive 8-s epochs of the trials; logistic functions were fitted to the data from each rat for the derivation of timing indices (T (50) [time corresponding to %B = 50]; Weber fraction). RESULTS: In experiment 1, DOI (0.25 mg kg(-1)) reduced T (50) compared to vehicle; tolerance to this effect was seen after repeated daily treatments with DOI if the rats were exposed to behavioural training during the period of treatment but not if the repeated treatments took place during a 'holiday' from behavioural training. In experiment 2, repeated treatment with DOI resulted in tolerance to the effect of DOI on T (50) and cross tolerance to the effect of d-amphetamine (0.4 mg kg(-1)), but no cross-tolerance was seen to the effect of quinpirole (0.08 mg kg(-1)). CONCLUSIONS: The results indicate that behavioural adaptation is involved in the development of tolerance to DOI's effect on timing. The finding of cross-tolerance to d-amphetamine but not to quinpirole suggests that the reduction of T (50) in the free-operant psychophysical procedure may be brought about by two distinct pharmacological mechanisms, one activated by DOI and d-amphetamine, and the other by quinpirole. PMID- 17333135 TI - A pharmaco-EEG study on antipsychotic drugs in healthy volunteers. AB - RATIONALE: Both psychotropic drugs and mental disorders have typical signatures in quantitative electroencephalography (EEG). Previous studies found that some psychotropic drugs had EEG effects opposite to the EEG effects of the mental disorders treated with these drugs (key-lock principle). OBJECTIVES: We performed a placebo-controlled pharmaco-EEG study on two conventional antipsychotics (chlorpromazine and haloperidol) and four atypical antipsychotics (olanzapine, perospirone, quetiapine, and risperidone) in healthy volunteers. We investigated differences between conventional and atypical drug effects and whether the drug effects were compatible with the key-lock principle. METHODS: Fourteen subjects underwent seven EEG recording sessions, one for each drug (dosage equivalent of 1 mg haloperidol). In a time-domain analysis, we quantified the EEG by identifying clusters of transiently stable EEG topographies (microstates). Frequency-domain analysis used absolute power across electrodes and the location of the center of gravity (centroid) of the spatial distribution of power in different frequency bands. RESULTS: Perospirone increased duration of a microstate class typically shortened in schizophrenics. Haloperidol increased mean microstate duration of all classes, increased alpha 1 and beta 1 power, and tended to shift the beta 1 centroid posterior. Quetiapine decreased alpha 1 power and shifted the centroid anterior in both alpha bands. Olanzapine shifted the centroid anterior in alpha 2 and beta 1. CONCLUSIONS: The increased microstate duration under perospirone and haloperidol was opposite to effects previously reported in schizophrenic patients, suggesting a key-lock mechanism. The opposite centroid changes induced by olanzapine and quetiapine compared to haloperidol might characterize the difference between conventional and atypical antipsychotics. PMID- 17333136 TI - Cognitive-motivational predictors of excessive drinkers' success in changing. AB - AIMS: The purpose of this study was to identify cognitive (alcohol attentional bias, AAB) and motivational (motivational structure, MS; readiness to change, RTC) predictors of changes in excessive drinking. MATERIALS AND METHODS: One hundred fifty-eight excessive drinkers not in treatment were administered a test battery and were re-tested 3 and 6 months later. The tests included the alcohol timeline followback, readiness to change questionnaire, alcohol Stroop (to measure AAB), personal concerns inventory (to measure MS), and a measure of family history of alcohol problems (FHAP). RESULTS: High RTC predicted short-term but not long-term reductions in drinking; both low AAB and high FHAP predicted long-term reductions. MS interacted with both AAB and RTC so that the greatest long-term drinking reductions occurred among participants with adaptive MS and low AAB and among those with adaptive MS and high RTC. CONCLUSION: It was concluded that (a) both cognitive and motivational factors affect the likelihood of drinking reductions and (b) a complete understanding of drinking problems should be formulated in terms of both cognitive and motivational variables. PMID- 17333137 TI - Antipsychotic profile of rolipram: efficacy in rats and reduced sensitivity in mice deficient in the phosphodiesterase-4B (PDE4B) enzyme. AB - RATIONALE: Recent studies provide evidence for reduced phosphodiesterase-4B (PDE4B) as a genetic susceptibility factor as well as suggesting an association of several single nucleotide polymorphisms (SNPs) in PDE4B that are associated with an increased incidence of schizophrenia. OBJECTIVES: The aim of the current study was to assess the activity of rolipram, a nonsubtype-selective PDE4 inhibitor, in several animal models predictive of antipsychotic-like efficacy and side-effect liability and to use PDE4B wild-type and knockout mice to begin to understand the subtypes involved in the activity of rolipram. RESULTS: In rats, rolipram antagonized both phencyclidine hydrochloride- and D-amphetamine-induced hyperactivity and inhibited conditioned avoidance responding (CAR). In PDE4B wild type mice, rolipram dose-dependently suppressed CAR (ED(50) = 2.4 mg/kg); however, in knockout mice, their sensitivity to rolipram at the higher doses (1.0 and 3.2 mg/kg) was reduced, resulting in a threefold shift in the ED(50) (7.3 mg/kg), suggesting PDE4B is involved, at least in part, with the activity of rolipram. Only the highest dose of rolipram (3.2 mg/kg) produced a modest but significant degree of catalepsy. CONCLUSIONS: Rolipram has a pharmacologic profile similar to that of the atypical antipsychotics and has low extrapyramidal symptom liability. These results suggest that PDE4B mediates the antipsychotic effects of rolipram in CAR and that the PDE4B-regulated cyclic adenosine monophosphate signaling pathway may play a role in the pathophysiology and pharmacotherapy of psychosis. PMID- 17333138 TI - Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydrocannabinol. AB - RATIONALE: Cannabis use may precipitate schizophrenia especially if the individual has a genetic vulnerability to this mental disorder. Human and animal research indicates that neuregulin 1 (Nrg1) is a susceptibility gene for schizophrenia. OBJECTIVES: The aim of this study was to investigate whether dysfunction in the Nrg1 gene modulates the behavioural effects of Delta(9) tetrahydrocannabinol (THC), the major psychotropic component of cannabis. MATERIALS AND METHODS: Heterozygous Nrg1 transmembrane-domain knockout mice (Nrg1 HET) were treated with acute THC (0, 5 or 10 mg/kg i.p.) 30 min before being tested using open field (OF), hole board (HB), light-dark (LD), elevated plus maze (EPM), social interaction (SI) and prepulse inhibition (PPI) tests. RESULTS: Nrg1 HET mice showed differences in baseline behaviour with regard to locomotor activity, exploration and anxiety. More importantly, they were more sensitive to the locomotor suppressant actions of THC compared to wild type-like (WT) mice. In addition, Nrg1 HET mice expressed a greater THC-induced enhancement in % PPI than WT mice. The effects of THC on anxiety-related behaviour were task-dependent, with Nrg1 HET mice being more susceptible than WT mice to the anxiogenic effects of THC in LD, but not in the EPM, SI and OF tests. CONCLUSIONS: Nrg1 HET mice were more sensitive to the acute effects of THC in an array of different behaviours including those that model symptoms of schizophrenia. It appears that variation in the schizophrenia-related neuregulin 1 gene alters the sensitivity to the behavioural effects of cannabinoids. PMID- 17333139 TI - Simultaneous determination of p-hydroxyacetophenone, chlorogenic acid, and caffeic acid in Herba Artemisiae Scopariae by capillary electrophoresis with electrochemical detection. AB - Capillary electrophoresis with electrochemical detection has been employed for the determination of p-hydroxyacetophenone, chlorogenic acid, and caffeic acid in Herba Artemisiae Scopariae (the dried sprout of Artemisia scoparia Waldst. et Kit.). The effects of several important factors, such as the concentration and the acidity of the running buffer, separation voltage, injection time, and detection potential, were investigated to acquire the optimum conditions. The detection electrode was a 300-microm-diameter carbon disc electrode at a working potential of +0.90 V (relative to the saturated calomel electrode). The three analytes can be well separated within 11 min in a 40-cm-long fused-silica capillary at a separation voltage of 15 kV in 50 mM borate buffer (pH 9.2). The relation between peak current and analyte concentration was linear over about 3 orders of magnitude, with detection limits (signal-to-noise ratio of 3) of 0.31, 0.39, and 0.50 microM for p-hydroxyacetophenone, chlorogenic acid, and caffeic acid, respectively. The proposed method has been successfully applied to monitor the three bioactive constituents in real plant samples and to differentiate between different herbal drugs with satisfactory assay results. PMID- 17333140 TI - Determination of total mercury and methylmercury in biological samples by photochemical vapor generation. AB - Cold vapor atomic absorption spectrometry (CV-AAS) based on photochemical reduction by exposure to UV radiation is described for the determination of methylmercury and total mercury in biological samples. Two approaches were investigated: (a) tissues were digested in either formic acid or tetramethylammonium hydroxide (TMAH), and total mercury was determined following reduction of both species by exposure of the solution to UV irradiation; (b) tissues were solubilized in TMAH, diluted to a final concentration of 0.125% m/v TMAH by addition of 10% v/v acetic acid and CH(3)Hg(+) was selectively quantitated, or the initial digests were diluted to 0.125% m/v TMAH by addition of deionized water, adjusted to pH 0.3 by addition of HCl and CH(3)Hg(+) was selectively quantitated. For each case, the optimum conditions for photochemical vapor generation (photo-CVG) were investigated. The photochemical reduction efficiency was estimated to be approximately 95% by comparing the response with traditional SnCl(2) chemical reduction. The method was validated by analysis of several biological Certified Reference Materials, DORM-1, DORM-2, DOLT-2 and DOLT 3, using calibration against aqueous solutions of Hg(2+); results showed good agreement with the certified values for total and methylmercury in all cases. Limits of detection of 6 ng/g for total mercury using formic acid, 8 ng/g for total mercury and 10 ng/g for methylmercury using TMAH were obtained. The proposed methodology is sensitive, simple and inexpensive, and promotes "green" chemistry. The potential for application to other sample types and analytes is evident. PMID- 17333141 TI - Enhancing high-throughput technology and microfluidics with FTIR spectroscopic imaging. PMID- 17333142 TI - In situ Raman spectroelectrochemistry of azobenzene monolayers on glassy carbon. AB - In situ Raman spectra of chemisorbed azobenzene (AB) monolayers on glassy carbon (GC) electrodes were observed under potentiostatic conditions in acetonitrile (ACN) with tetrabutyl-ammonium tetrafluoroborate (TBA-BF4). The Raman intensities of these spectra were high below -1000 mV, and this is attributed to the change in absorbance of AB on GC. In this paper, we describe chemisorbed AB molecules on GC electrode surfaces under potentiostatic conditions. PMID- 17333143 TI - Detection of antibiotics in food: extraction of fluoroquinolones by DNA. AB - The ability of DNA to extract fluoroquinolones from model solutions and real probes of food was demonstrated and investigated quantitatively. The interaction between fluoroquinolones and different types of DNA was studied by equilibrium dialysis. The first application of this direct approach allowed us to determine binding constants and binding stoichiometries in different conditions. The binding of enrofloxacin to heat-denatured DNA (d-DNA) from herring sperm is pH- and magnesium-dependent; the highest fraction of bound drugs was found at pH 7 and a magnesium concentration of 0.5-1 mM. Results for three types of DNA: d-DNA, double-stranded DNA and single-stranded DNA were compared. The unwound DNA showed almost doubled binding constants and stoichiometries, thus indicating preferable interaction of enrofloxacin with single-strand regions of DNA. The binding of other fluoroquinolones (lomefloxacin, ciprofloxacin, norfloxacin, danofloxacin and sarafloxacin) with d-DNA is very similar to that of enrofloxacin: the binding constants are in the range from 0.94x10(5) to 2.40x10(5) M-1, and the stoichiometries range from 4.1 to 6.9 fluoroquinolone molecules per 100 DNA bases. The binding properties were quantitatively the same for extraction of fluoroquinolones from model aqueous solutions and from liquid food (milk). The results indicate the efficiency of DNA for selective extraction of fluoroquinolones from real samples for further analysis. This selective binding also allows us to consider DNA as a natural receptor for development of analytical techniques for fluoroquinolones. PMID- 17333144 TI - Laboratory simulation of Hg0 emissions from a snowpack. AB - Snow surfaces play an important role in the biogeochemical cycle of mercury in high-latitude regions. Snowpacks act both as sources and sinks for gaseous compounds. Surprisingly, the roles of each environmental parameter that can govern the air-surface exchange over snow are not well understood owing to the lack of systematic studies. A laboratory system called the laboratory flux measurement system was used to study the emission of gaseous elemental mercury from a natural snowpack under controlled conditions. The first results from three snowpacks originating from alpine, urban and polar areas are presented. Consistent with observations in the field, we were able to reproduce gaseous mercury emissions and showed that they are mainly driven by solar radiation and especially UV-B radiation. From these laboratory experiments, we derived kinetic constants which show that divalent mercury can have a short natural lifetime of about 4-6 h in snow. PMID- 17333145 TI - Simultaneous determination of speciation parameters of Cu, Pb, Cd and Zn in model solutions of Suwannee River fulvic acid by pseudopolarography. AB - There is a growing awareness of the importance of quantitative determinations of speciation parameters of the trace metals Cu, Zn, Cd and Pb in aqueous samples containing chemically heterogeneous humic substances, especially when they are present together, interacting with one another and competing for specific binding sites of the humic substances. Such determinations require fundamental knowledge and understanding of these complex interactions, gained through basic laboratory based studies of well-characterized humic substances in model solutions. Since the chemical heterogeneity of humic substances plays an important role in the thermodynamics (stability) and kinetics (lability) of trace metal competition for humic substances, a metal speciation technique such as pseudopolarography that can reveal the special, distinctive nature of metal complexation is required, and it was therefore used in this study. A comparison of the heterogeneity parameters (Gamma) for Zn(II), Cd(II), Pb(II) and Cu(II) complexes in model solutions of Suwannee River fulvic acid (SRFA) shows that GammaCd>GammaZn>GammaPb>GammaCu, suggesting that SRFA behaves as a relatively homogeneous complexant for Zn(II) and Cd(II), whereas it behaves as a relatively heterogeneous complexant for Pb(II) and an even more heterogeneous complexant for Cu(II) under the experimental conditions used. The order of values of log K* (from the differential equilibrium function, DEF) for the trace metals at pH 5.0 follow the sequence: log K*Cu>log K*Pb>log K*Zn>log K*Cd. These results are in good agreement with the literature values. The results of this work suggest the possibility of simultaneously determining several metals in a sample in a single experiment, and hence in a shorter time than required for multiple experiments. PMID- 17333146 TI - Electromagnetic and chemical interaction between Ag nanoparticles and adsorbed rhodamine molecules in surface-enhanced Raman scattering. AB - The critical importance of the junction between touching or closely adjacent Ag nanoparticles associated with single-molecule sensitivity (SMS) in surface enhanced Raman scattering (SERS) was confirmed via the following observations: (1) an additional peak is observed in elastic scattering only for the SERS-active state, which originated from absorption of adsorbates, (2) local- and far-field evaluation using a finite difference time domain method could reproduce this extra peak and anticipate the significantly enhanced field even inside the adsorbates sitting at the junction through an increased coupling of the localized surface plasmons, and (3) in addition to enhanced fluorescence of adsorbed dye, an inelastic scattering peak was observed and attributed to the metal surface electron. Concerning the chemical enhancement in SERS, Cl- anions activate the Ag Cl-R6G (rhodamine) samples by inducing intrinsic electronic interaction between Ag and R6G molecules. This electronic interaction is irreversibly quenched by the addition of thiosulfate anions which dissolve Ag+ cations while the electromagnetic (EM) effect remains intact. PMID- 17333147 TI - Label-free voltammetric detection of single-nucleotide mismatches recognized by the protein MutS. AB - MutS, a protein involved in DNA mismatch repair, recognizes mispaired and unpaired bases in duplex DNA. We have previously used MutS in an electrochemical double-surface technique (DST) for in-vitro detection of point mutations in DNA. The DST involved binding of unlabeled MutS to DNA heteroduplexes at the surface of magnetic beads followed by a highly sensitive electrochemical determination of the protein by measurement of a catalytic protein signal (peak H) at mercury electrodes. Detection of MutS using a peak resulting from oxidation of tyrosine and tryptophan residues of the protein at a carbon-paste electrode (CPE) was also possible but was approximately three orders of magnitude less sensitive. In this work we present an optimized technique for ex-situ voltammetric determination of MutS at a CPE. Choice of optimum experimental conditions (pH of supporting electrolyte, square-wave voltammetry settings, etc.) resulted in substantial improvement of the sensitivity of the assay, enabling detection of approximately 140 pg (1.6 fmol protein monomer) MutS in a 5-microL sample. The sensitivity was increased further by acid hydrolysis of the protein before measurement. The hydrolyzed protein was detectable down to 5 pg (approx. 56 amol) MutS in 5 microL solution. By using the DST combined with determination of the bound unlabeled MutS at the CPE we demonstrated selective interactions of the protein with single base mismatches and discrimination among different base mispairs in 30-mer or 95 mer DNA duplexes. In agreement with previous studies, binding of the protein to the 30-mer substrates followed the trend G:T>>C:A>A:A>C:T>homoduplex. The electrochemical data were confirmed by use of an independent technique-a quartz crystal microbalance for real-time monitoring of MutS interactions with DNA duplexes containing different base mispairs. By using the electrochemical DST a G:T mismatch was detectable in up to 1000-fold excess of homoduplex DNA. PMID- 17333148 TI - Assessment of metastable atom bombardment (MAB) ionization mass spectrometry for the fast determination of heterocyclic aromatic amines in cooked meat. AB - An investigation of metastable atom bombardment (MAB) ionization mass spectrometry for the fast characterization of mutagenic/carcinogenic heterocyclic aromatic amines (HAAs) formed during heating processes of meats is presented. The aim of our study was to use the selective ionization of MAB to develop a detection method for HAAs in non-purified meat extracts, thus avoiding purification and concentration steps and reducing analysis time. Sample introduction into the MAB ion source was achieved by pyrolysis, allowing the direct and fast insertion of complex food extracts into the mass spectrometer. Analysis conditions were optimized on standard HAAs by using different ionization gases for the MAB process. Metastable nitrogen was selected as the best MAB gas for the analysis of HAAs. Ionization selectivity is shown by the detection of heterocyclic amines in non-purified chicken meat extracts spiked with HAAs. A quantitative approach is also presented by using pyrograms as chromatograms for quantification purposes. HAAs determination using Py-MAB-ToF was finally performed on cooked chicken breast extracts and compared to an LC-APCI-MS/MS method. Although Py-MAB-ToF sensitivity remains to be improved in the present state of development of our prototype device, only 2 h from the cooking were required to obtain quantitative results in good agreement with HAAs concentrations measured by LC-MS/MS in 36 h. Figure Experimental set-up for pyrolysis-MAB-ToF mass spectrometry experiments. PMID- 17333149 TI - Stacking and quantitative analysis of lovastatin in urine samples by the transient moving chemical reaction boundary method in capillary electrophoresis. AB - A simple, sensitive, and useful concentration method for lovastatin (Lvt) in urine has been developed based on the transient moving chemical reaction boundary method (tMCRBM) in capillary electrophoresis. The MCRB is formed with acidic sample buffer (Gly-HCl) and alkaline running buffer (Gly-NaOH). The following optimal conditions were determined for stacking and separation: electrophoretic buffer of 100 mM Gly- NaOH (pH 11.52), sample buffer of 20 mM Gly-HCl (pH 4.93), fused-silica capillary of 76 cm x 75-microm i.d (67 cm from detector), sample injection at 14 mbar for 3 min. A 21- to 26-fold increase in peak height was achieved for detection of Lvt in urine under the optimal conditions compared with normal capillary zone electrophoresis. By combining the sample pretreatment procedure with the stacking method, the sensitivity of Lvt in urine was increased by 105- to 130-fold. The limits of detection (LOD) and quantification (LOQ) for Lvt in urine were decreased to 8.8 ng/mL and 29.2 ng/mL, respectively. The intra day and inter-day precision values (expressed as RSD) were 2.23-3.61% and 4.03 5.05%, respectively. The recoveries of the analyte at three concentration levels changed from 82.65 to 100.49%. PMID- 17333150 TI - Towards rapid nanoscale chemical analysis using tip-enhanced Raman spectroscopy with Ag-coated dielectric tips. AB - The influence of dielectric substrates on the Raman scattering activities of Ag overlayers has been investigated. Materials with low refractive indices, such as SiO(2), SiO(x) and AlF(3), were found to provide suitable supporting platforms for Ag films to give strong surface-enhanced Raman scattering for dye molecules when illuminated at 488 nm. This finding was then extended to tip-enhanced Raman scattering (TERS). Huge enhancements of 70-80x, corresponding to net enhancements of >10(4), were observed for brilliant cresyl blue test analyte when Ag-coated tips made from or precoated with low refractive index materials were applied. The yield of fabricated tips that significantly enhance the Raman signals was found to be close to 100%. These findings provide crucial steps towards the use of TERS as a robust technique for rapid chemical imaging with nanometer spatial resolution. Figure Silver-coated dielectric tips for tip-enhanced Raman scattering (TERS) are capable of more than 10,000-fold enhancement. PMID- 17333151 TI - Vapour-generation analytical chemistry: from Marsh to multimode sample introduction system. AB - The history and state of knowledge of techniques available to analysts before the development of modern spectrometric techniques are surveyed in this paper. A variety of evaluative methods developed in the 19th century, with relatively minor improvements, remain in the repertoire of analysts even though they are at best semi-quantitative. Interferences with the vapour-generation reaction were identified early, as were the advantages and drawbacks of electrochemical vapour generation. This review attempts to present the earliest descriptions of vapour generation of elements and of the devices that have been used for their determination; phase-separation devices, in particular, are described. PMID- 17333152 TI - Application of a sensitive fluorometric HPLC assay to determine the sialic acid content of infant formulas. AB - The developing human brain requires high amounts of sialic acids. While human milk is very rich in sialic acids, cow's milk based infant formulas provide lower amounts of sialic acids, and sialic acids are absent in soy milk based formulas. This has prompted interest in the supplementation of formulas with sialic acids, either free or bound to glycoconjugates. In order for fortification of infant formulas with sialic acids to be appropriate for the developmental needs of the infant, an accurate quantitation of sialic acid content of infant formulas through a reliable and easy-to-use method is, therefore, of great interest to industry. In the present method, we describe the application of one of the most widely used analytical techniques to the quantitation of sialic acids in infant formulas. Briefly, sialic acids are hydrolyzed from glycoconjugates, derivatized using 1,2-diamino-4,5-methylenedioxybenzene dihydrochloride (DMB), and separated using reversed-phase high-performance liquid chromatography. The method fulfilled the established criteria for validation, with an interassay standard deviation of less than 5%, accuracy greater than 97%, and surrogate recovery between 98 and 104%. An investigation of the ruggedness of the method identified two key criteria: both standards and samples must be subjected to the same temperature and pH conditions for an accurate quantitation; and prolonged storage (more than 2 days) of the DMB reagent and derivatives must be avoided. In conclusion, this method is specific, straightforward, and accurate and can be easily performed in a quality-assurance laboratory to track the level of sialic acid in formulas that contain both inherent and fortified amounts of sialic acids. Figure Infant formula and HPLC vials used for the sialic acid quantitation. PMID- 17333153 TI - Study of a new derivatizing reagent that improves the analysis of amino acids by HPLC with fluorescence detection: application to hydrolyzed rape bee pollen. AB - A simple and sensitive method for evaluating the chemical compositions of protein amino acids, including cystine (Cys)(2) and tryptophane (Try) has been developed, based on the use of a sensitive labeling reagent 2-(11H-benzo[alpha]-carbazol-11 yl) ethyl chloroformate (BCEC-Cl) along with fluorescence detection. The chromophore of the 1,2-benzo-3,4-dihydrocarbazole-ethyl chloroformate (BCEOC-Cl) molecule was replaced with the 2-(11H-benzo[alpha]-carbazol-11-yl) ethyl functional group, yielding the sensitive fluorescence molecule BCEC-Cl. The new reagent BCEC-Cl could then be substituted for labeling reagents commonly used in amino acid derivatization. The BCEC-amino acid derivatives exhibited very high detection sensitivities, particularly in the cases of (Cys)(2) and Try, which cannot be determined using traditional labeling reagents such as 9-fluorenyl methylchloroformate (FMOC-Cl) and ortho-phthaldialdehyde (OPA). The fluorescence detection intensities for the BCEC derivatives were compared to those obtained when using FMOC-Cl and BCEOC-Cl as labeling reagents. The ratios I (BCEC)/I (BCEOC) = 1.17-3.57, I (BCEC)/I (FMOC) = 1.13-8.21, and UV(BCEC)/UV(BCEOC) = 1.67 4.90 (where I is the fluorescence intensity and UV is the ultraviolet absorbance). Derivative separation was optimized on a Hypersil BDS C(18) column. The detection limits calculated from 1.0 pmol injections, at a signal-to-noise ratio of 3, ranged from 7.2 fmol for Try to 8.4 fmol for (Cys)(2). Excellent linear responses were observed, with coefficients of >0.9994. When coupled with high-performance liquid chromatography, the method established here allowed the development of a highly sensitive and specific method for the quantitative analysis of trace levels of amino acids including (Cys)(2) and Try from bee collected pollen (bee pollen) samples. PMID- 17333154 TI - Wax components of larval cocoon silk of the hornet Vespa analis Fabricius. AB - Wax, 85% of which consists of orthorhombic crystals, has been found in the cocoon of the hornet Vespa analis Fabricius by means of high-resolution (13)C solid state nuclear magnetic resonance (NMR). GC-MS analysis revealed the major components of the wax in the cocoon were linear alkenes and alkanes with a total of 23 or 34 carbon atoms. At 40.7 degrees C a DSC absorption peak and a (13)C NMR chemical shift change were observed and interpreted as the result of a crystal transition from the orthorhombic to rotator phase of the wax molecules. At 55.5 degrees C melting of the wax was observed. The amount of crystalline wax deposition varied with the part of the cocoon-crystalline wax was concentrated in the silk sleeve lining the inner wall of each comb cell but there was very little in the silk cap projecting from the end of each cell. Because the wax components of the larval cocoon were almost identical to those of the larval cuticle, despite a slight difference in the profiles, they might have come from the larval cuticle via direct body contact with the cocoon. PMID- 17333156 TI - Cation identity dependence of crown ether photonic crystal Pb2+ sensing. AB - We quantitatively modeled the volume phase transition of a hydrogel containing a crystalline colloidal array with a crown ether ligand which binds Pb2+. The hydrogel volume response and the wavelength diffracted depend on the Pb2+ concentration and on both the ionic strength and the valence of the nonbinding ionic species. We successfully modeled the response of this hydrogel Pb2+ sensor to ionic strength and the cation valence of the added salts. PMID- 17333157 TI - Lack of impact of artesunate on the disposition kinetics of sulfadoxine/pyrimethamine when the two drugs are concomitantly administered. AB - OBJECTIVE: To determine the effect of artesunate (AT) on the disposition kinetics of sulfadoxine/pyrimethamine (SP) in humans. METHODS: In a randomized cross-over study, 16 healthy volunteers were given a dose of three SP tablets containing 500 mg of sulfadoxine (SDX) and 25 mg of pyrimethamine (PYR) (=SP group), while the second arm received three SP tablets + two AT tablets of 200 mg in total followed by 100 mg AT for the next 4 days (SP+AT group). Blood samples (100 microl) were collected by means of a finger prick and dried on filter paper. The blood spots were wrapped in polythene folders and stored at room temperature until analysis. The samples were assayed using high-performance liquid chromatographic methods. RESULTS: The peak concentration C(max)), time required to attain peak concentration (T(max)), half-life (t ((1/2))) and area under the plasma concentration-time curve (AUC) were determined. The C(max) of SDX were 92.9 and 98.9 microg/ml for the SP and SP+AT arms, respectively; for PYR, these were 0.86 and 0.79 microg/ml, respectively. The T(max) of SDX were 10 and 8 h for the SP and SP+AT arms, respectively; for PYR, these were 4.0 and 3.0 h, respectively. The AUC(0-288) of SDX were 15,840 and 18,876 microg/ml h for the SP and SP+AT arms, respectively; for PYR, they were 124 and 112 microg/ml h, respectively. The t ((1/2)) of values for SDX were 165 and 180 h for the SP and SP+AT arms, respectively; for PYR, these were 158 and 177 h, respectively. There was no statistically significant difference between the C(max), T(max), AUC(0-288) and t ((1/2)) between the two arms (p > 0.05). CONCLUSION: Taking AT concomitantly with SP does not have any impact in the disposition of SP. PMID- 17333158 TI - Does coronary artery bypass surgery affect metoprolol bioavailability. AB - BACKGROUND: beta-blockers are commonly administered in patients with coronary artery bypass surgery (CABG). Despite this therapy, however, the incidence of postoperative atrial fibrillation (AF) is high (9-19%), and it is unknown why the beta-blockers do not reduce the incidence of AF more efficiently. In this pharmacokinetics study, in which the patients acted as their own controls, we have evaluated the bioavailability of perioperative metoprolol tablets in CABG surgery patients. METHODS: Twelve male patients, aged 45-64 years, scheduled for CABG surgery were administered an initial 50 mg metoprolol tartrate tablet orally on the morning of the preoperative day and thereafter at 12-h intervals. Regular blood samples were collected up to 12 h after the first administration of the drug on the preoperative day as well on the first and third postoperative days. The plasma concentration for metoprolol was analyzed (limit of quantification = 0.001 mg/L) using liquid chromatography-tandem mass spectrometry. RESULTS: The bioavailability of the metoprolol was significantly less on the first postoperative day, with AUC(0-12) values ranging from 0.7 to 17.1 (median: 7.2) mg min/L, than on the preoperative day, with AUC(0-12) values of 5.1-26.7 (12.6) mg min/L; however, it returned to the preoperative values on the third postoperative day, with AUC(0-12) values of 3.5-25.2 (15.2) mg min/L. Similar changes were observed in C(max) values: preoperative C(max) ranged between 0.026 and 0.123 (0.060) mg/L, on the first postoperative day, the C(max) ranged between 0.003 and 0.093 (0.025) mg/L, and on the third postoperative day, the C(max) ranged between 0.009 and 0.136 (0.061) mg/L. There was no correlation between the pharmacokinetic parameters and patient characteristics, but both the preoperative C(max) and C(60) correlated significantly with the postoperative C(max) (Pearson correlation coefficient: 0.61-0.72). One patient with one of the lowest rates and extent of metoprolol absorption developed AF. CONCLUSION: This study indicates that the bioavailability of metoprolol is markedly reduced when administered in tablet form during the early phase after CABG. PMID- 17333159 TI - Stereoselective interaction between the CYP2C8 inhibitor gemfibrozil and racemic ibuprofen. AB - OBJECTIVE: Ibuprofen, a nonsteroidal anti-inflammatory agent, is metabolised in vitro by cytochrome P450 (CYP) 2C8 and 2C9. We studied the possible effect of gemfibrozil, an in vivo inhibitor of CYP2C8, on the pharmacokinetics of ibuprofen in healthy volunteers. METHODS: In a randomised two-phase crossover study, 10 healthy volunteers took 600 mg gemfibrozil or placebo orally twice daily for 3 days. On day 3, each subject ingested 400 mg of racemic ibuprofen. Plasma concentrations of ibuprofen enantiomers and gemfibrozil were measured. RESULTS: Gemfibrozil raised the mean total area under the plasma concentration-time curve (AUC(0-infinity)) of R-ibuprofen by 34% (range -10 to 67%; P < 0.001). The elimination half-lives (t (1/2)) of R- and S-ibuprofen were increased by 54 and 34% (range 11-162% and 16-85%; P < 0.001) respectively. The other pharmacokinetic variables of R- and S-ibuprofen were not changed significantly. The AUC(0 infinity) ratio of R-ibuprofen to S-ibuprofen was increased by gemfibrozil (P < 0.001). CONCLUSIONS: Gemfibrozil moderately increases the AUC(0-infinity) of R ibuprofen and prolongs its t (1/2), indicating that R-ibuprofen is partially metabolised by CYP2C8. The interconversion of R- to S-ibuprofen can explain the small effect of gemfibrozil on the t (1/2) of S-ibuprofen. The gemfibrozil ibuprofen interaction is of limited clinical significance. PMID- 17333160 TI - Decreased serum activity of semicarbazide-sensitive amine oxidase (SSAO) in patients treated with second generation antipsychotics: a link to impaired glucose metabolism? AB - OBJECTIVE: Although the treatment of schizophrenia with many second generation antipsychotics is known to be associated with metabolic changes, such as hyperglycemia or hypercholesterolemia, the underlying mechanisms of these adverse reactions remain unclear. In light of the recent focus on the involvement of semicarbazide-sensitive amine oxidase (SSAO) in glucose metabolism, we investigated SSAO serum activity in schizophrenic patients treated with antipsychotics with the objective of determining a possible link between SSAO and impaired glucose metabolism. METHODS: Blood samples were drawn from 44 schizophrenic patients (24 receiving second generation antipsychotics known to disturb glucose metabolism) on day 1 and day 5 of inpatient treatment. Forty-one healthy adults with no medical condition known to influence SSAO served as controls. RESULTS: Of the 44 schizophrenic patients, the 24 treated with second generation antipsychotics known to disturb glucose metabolism showed significantly lower SSAO serum activity [day 1 (mean +/- SD): 477 +/- 105 mU/L; day 5: 438 +/- 86 mU/L] than the 20 patients treated with other antipsychotics not known to influence glucose metabolism (day 1: 513 +/- 124 mU/L, p = 0.359; day 5: 542 +/- 204 mU/L, p = 0.021) only after 5 days of treatment and compared to healthy controls (526 +/- 142 mU/L, p = 0.021). No differences were observed between schizophrenic patients treated with first generation antipsychotics and the controls. CONCLUSION: We found decreased SSAO serum activity exclusively in schizophrenic patients treated with second generation antipsychotics known to disturb glucose metabolism. In terms of the role of SSAO in glucose metabolism, the observed decrease in SSAO serum activity may be linked to metabolic changes that are known to occur in schizophrenic patients being treated with many second generation antipsychotics. PMID- 17333161 TI - Idiopathic inflammatory-demyelinating diseases of the central nervous system. AB - Idiopathic inflammatory-demyelinating diseases (IIDDs) include a broad spectrum of central nervous system disorders that can usually be differentiated on the basis of clinical, imaging, laboratory and pathological findings. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. The relapsing-remitting and secondary progressive forms of multiple sclerosis (MS) are the most common IIDDs. Other MS phenotypes include those with a progressive course from onset (primary progressive and progressive relapsing) or with a benign course continuing for years after onset (benign MS). Uncommon forms of IIDDs can be classified clinically into: (1) fulminant or acute IIDDs, such as the Marburg variant of MS, Balo's concentric sclerosis, Schilder's disease, and acute disseminated encephalomyelitis; (2) monosymptomatic IIDDs, such as those involving the spinal cord (transverse myelitis), optic nerve (optic neuritis) or brainstem and cerebellum; and (3) IIDDs with a restricted topographical distribution, including Devic's neuromyelitis optica, recurrent optic neuritis and relapsing transverse myelitis. Other forms of IIDD, which are classified clinically and radiologically as pseudotumoral, can have different forms of presentation and clinical courses. Although some of these uncommon IIDDs are variants of MS, others probably correspond to different entities. MR imaging of the brain and spine is the imaging technique of choice for diagnosing these disorders, and together with the clinical and laboratory findings can accurately classify them. Precise classification of these disorders may have relevant prognostic and treatment implications, and might be helpful in distinguishing them from tumoral or infectious lesions, avoiding unnecessary aggressive diagnostic or therapeutic procedures. PMID- 17333163 TI - Load-dependent release limits the processive stepping of the tetrameric Eg5 motor. AB - Tetrameric motor proteins of the Kinesin-5 family are essential for eukaryotic cell division. The microscopic mechanism by which Eg5, the vertebrate Kinesin-5, drives bipolar mitotic spindle formation remains unknown. Here we show in optical trapping experiments that full-length Eg5 moves processively and stepwise along microtubule bundles. Interestingly, the force produced by individual Eg5 motors typically reached only approximately 2 pN, one-third of the stall force of Kinesin-1. Eg5 typically detached from microtubules before stalling. This behavior may reflect a regulatory mechanism important for the role of Eg5 in the mitotic spindle. PMID- 17333162 TI - Hydration of POPC bilayers studied by 1H-PFG-MAS-NOESY and neutron diffraction. AB - The stability of lipid bilayers is ultimately linked to the hydrophobic effect and the properties of water of hydration. Magic angle spinning (MAS) nuclear Overhauser enhancement spectroscopy (NOESY) with application of pulsed magnetic field gradients (PFG) was used to study the interaction of water with 1-palmitoyl 2-oleoyl-sn-glycero-3-phosphocholine bilayers in the fluid phase. NOESY cross relaxation between water and polar groups of lipids, but also with methylene resonances of hydrophobic hydrocarbon chains, has been observed previously. This observation led to speculations that substantial amounts of water may reside in the hydrophobic core of bilayers. Here, the results of a quantitative analysis of cross-relaxation in a lipid 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (POPC)/water mixture are reported. Coherences were selected via application of pulsed magnetic field gradients. This technique shortens acquisition times of NOESY spectra to 20 min and reduces t (1)-spectral noise, enabling detection of weak crosspeaks, like those between water and lipids, with higher precision than with non-gradient NOESY methods. The analysis showed that water molecules interact almost exclusively with sites of the lipid-water interface, including choline, phosphate, glycerol, and carbonyl groups. The lifetime of lipid-water associations is rather short, on the order of 100 ps, at least one order of magnitude shorter than the lifetime of lipid-lipid associations. The distribution of water molecules over the lipid bilayer was measured at identical water content by neutron diffraction. Water molecules penetrate deep into the interfacial region of bilayers but water concentration in the hydrophobic core is below the detection limit of one water molecule per lipid, in excellent agreement with the cross-relaxation data. PMID- 17333164 TI - Free energies of binding of R- and S-propranolol to wild-type and F483A mutant cytochrome P450 2D6 from molecular dynamics simulations. AB - Detailed molecular dynamics (MD) simulations have been performed to reproduce and rationalize the experimental finding that the F483A mutant of CYP2D6 has lower affinity for R-propranolol than for S-propranolol. Wild-type (WT) CYP2D6 does not show this stereospecificity. Four different approaches to calculate the free energy differences have been investigated and were compared to the experimental binding data. From the differences between calculations based on forward and backward processes and the closure of thermodynamic cycles, it was clear that not all simulations converged sufficiently. The approach that calculates the free energies of exchanging R-propranolol with S-propranolol in the F483A mutant relative to the exchange free energy in WT CYP2D6 accurately reproduced the experimental binding data. Careful inspection of the end-points of the MD simulations involved in this approach, allowed for a molecular interpretation of the observed differences. PMID- 17333165 TI - Polymorphisms in the Paan-AG promoter influence NF-kappaB binding and transcriptional activity. AB - The human leukocyte antigen-G (HLA-G) gene encodes a protein that is highly expressed at the human maternal-fetal interface during pregnancy and may be critical to the survival of the semiallogenic fetus. A unique feature of this gene is a 13-bp deletion in the proximal promoter that renders it unresponsive to transactivation by the nuclear factor-kappaB (NF-kappaB). We previously showed that the proximal promoter of Paan-AG, the functional homologue of HLA-G in the olive baboon (Papio anubis), is intact. We cloned the promoters of two putative Paan-AG alleles (AG1 and AG2) and identified a number of regulatory elements including two kappaB sites. In the current study, binding and activity of the two kappaB elements in each putative allele were assessed by electrophoretic mobility shift and supershift assays. Functional activity was determined using luciferase reporter assays. The kappaB1 and kappaB2 elements in AG1 bound NF-kappaB with similar affinity. In contrast, the kappaB1 element of AG2 bound NF-kappaB with a much higher affinity than AG-1 kappaB1 (a 30-fold increase), whereas kappaB2 did not bind. Mutagenesis analysis showed that the difference in binding intensities was due to two nucleotides in the 3' end of kappaB1. Similarly, failure of AG2 kappaB2 binding was a result of the last nucleotide in the 3' end that differed from the consensus; mutating this nucleotide to match the consensus reestablished binding. Functional activity of the two putative alleles also differed; AG1 luciferase activity was consistently lower than that of AG2. Mutating the last two nucleotides in the 3' end of AG1 kappaB1 resulted in increased luciferase activity to levels comparable to that of AG2. Overall, these results show that in vitro variations in the promoter region may influence transcription of Paan-AG. PMID- 17333168 TI - Microbial enzymes involved in lactone compound metabolism and their biotechnological applications. AB - Lactone compounds are widely distributed in nature and play important roles in organisms. These compounds are synthesized and metabolized enzymatically in vivo; however, detailed investigation of these enzymes lags behind that of other common enzymes. In this paper, recent work on the enzymes involved in the metabolism of lactone compounds will be reviewed. In particular, fundamental and application studies on lactonases and Baeyer-Villiger monooxgenases of microbial origin are described. PMID- 17333166 TI - The SPINK gene family and celiac disease susceptibility. AB - The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was determined for all four SPINK genes by quantitative reverse-transcription polymerase chain reaction in duodenal biopsy samples from untreated (n=15) and diet-treated patients (n=31) and controls (n=16). Genetic association of the four SPINK genes was tested within a total of 18 haplotype tagging SNPs, one coding SNP, 310 patients, and 180 controls. The SPINK4 study cohort was further expanded to include 479 CD cases and 540 controls. SPINK4 DNA sequence analysis was performed on six members of a multigeneration CD family to detect possible point mutations or deletions. SPINK4 showed differential gene expression, which was at its highest in untreated patients and dropped sharply upon commencement of a gluten-free diet. Genetic association tests for all four SPINK genes were negative, including SPINK4 in the extended case/control cohort. No SPINK4 mutations or deletions were observed in the multigeneration CD family with linkage to chromosome 9p21-13 nor was the coding SNP disease-specific. SPINK4 exhibits CD pathology-related differential gene expression, likely derived from altered goblet cell activity. All of the four SPINK genes tested do not contribute to the genetic risk for CD in the Dutch population. PMID- 17333167 TI - Effect of pyruvate dehydrogenase complex deficiency on L-lysine production with Corynebacterium glutamicum. AB - Intracellular precursor supply is a critical factor for amino acid productivity of Corynebacterium glutamicum. To test for the effect of improved pyruvate availability on L-lysine production, we deleted the aceE gene encoding the E1p enzyme of the pyruvate dehydrogenase complex (PDHC) in the L-lysine-producer C. glutamicum DM1729 and characterised the resulting strain DM1729-BB1 for growth and L-lysine production. Compared to the host strain, C. glutamicum DM1729-BB1 showed no PDHC activity, was acetate auxotrophic and, after complete consumption of the available carbon sources glucose and acetate, showed a more than 50% lower substrate-specific biomass yield (0.14 vs 0.33 mol C/mol C), an about fourfold higher biomass-specific L-lysine yield (5.27 vs 1.23 mmol/g cell dry weight) and a more than 40% higher substrate-specific L-lysine yield (0.13 vs 0.09 mol C/mol C). Overexpression of the pyruvate carboxylase or diaminopimelate dehydrogenase genes in C. glutamicum DM1729-BB1 resulted in a further increase in the biomass specific L-lysine yield by 6 and 56%, respectively. In addition to L-lysine, significant amounts of pyruvate, L-alanine and L-valine were produced by C. glutamicum DM1729-BB1 and its derivatives, suggesting a surplus of precursor availability and a further potential to improve L-lysine production by engineering the L-lysine biosynthetic pathway. PMID- 17333169 TI - Novel enzyme reactions related to the tricarboxylic acid cycle: phylogenetic/functional implications and biotechnological applications. AB - The tricarboxylic acid (TCA) cycle is an energy-producing pathway for aerobic organisms. However, it is widely accepted that the phylogenetic origin of the TCA cycle is the reductive TCA cycle, which is a non-Calvin-type carbon-dioxide fixing pathway. Most of the enzymes responsible for the oxidative and reductive TCA cycles are common to the two pathways, the difference being the direction in which the reactions operate. Because the reductive TCA cycle operates in an energetically unfavorable direction, some specific mechanisms are required for the reductive TCA-cycle-utilizing organisms. Recently, the molecular mechanism for the "citrate cleavage reaction" and the "reductive carboxylating reaction from 2-oxoglutarate to isocitrate" in Hydrogenobacter thermophilus have been demonstrated. Both of these reactions comprise two distinct consecutive reactions, each catalyzed by two novel enzymes. Sequence analyses of the newly discovered enzymes revealed phylogenetic and functional relationships between other TCA-cycle-related enzymes. The occurrence of novel enzymes involved in the citrate-cleaving reaction seems to be limited to the family Aquificaceae. In contrast, the key enzyme in the reductive carboxylation of 2-oxoglutarate appears to be more widely distributed in extant organisms. The four newly discovered enzymes have a number of potential biotechnological applications. PMID- 17333170 TI - Astaxanthin production by Phaffia rhodozyma and Haematococcus pluvialis: a comparative study. AB - Phaffia rhodozyma (now Xanthophyllomyces dendrorhous) and Haematococcus pluvialis are known as the major prominent microorganisms able to synthesize astaxanthin natural pigment. Important research efforts have been made to determine optimal conditions for astaxanthin synthesis. When the focus is on astaxanthin production, the maximal reported value of 9.2 mg/g cell is obtained within H. pluvialis grown on BAR medium, under continuous illumination (345 micromol photon m(-2) s(-1)) and without aeration. Whereas fermentation by mutated R1 yeast grown on coconut milk produced 1,850 microg/g yeast. However, when looking at astaxanthin productivity, the picture is slightly different. The figures obtained with P. rhodozyma are rather similar to those of H. pluvialis. Maximal reported values are 170 microg/g yeast per day with a wild yeast strain and 370 microg/g yeast per day with mutated R1 yeast. In the case of H. pluvialis, maximal values ranged from 290 to 428 microg/g cell per day depending on the media (BG-11 or BAR), light intensity (177 micromol photon m(-2) s(-1)), aeration, etc. The main aim of this work was to examine how astaxanthin synthesis, by P. rhodozyma and H. pluvialis, could be compared. The study is based on previous works by the authors where pigment productions have been reported. PMID- 17333171 TI - 5-Aminolevulinate production with recombinant Escherichia coli using a rare codon optimizer host strain. AB - The 5-aminolevulinate (ALA) synthase gene (hemA) containing several codons rarely used by Escherichia coli was cloned from the genome of Rhodobacter sphaeroides and optimized in two strains of Escherichia coli: BL21(DE3) and Rosetta(DE3), which is a rare codon optimizer strain. The effects of initial isopropyl-beta-D: thiogalactopyranoside (IPTG) concentration, induction time, and temperature on enzyme activity were studied and compared for two strains. The results indicated that the ALA synthase expressed by Rosetta(DE3)/pET-28a(+)-hemA was higher than that by BL21(DE3)/pET-28a(+)-hemA. The initial precursors, glycine and succinate, and initial glucose, which is an inhibitor for both ALA synthase and dehydratase, were observed to be the key factors affecting ALA production. ALA synthase activity was generally higher with Rosetta(DE3) than with BL21(DE3), so was ALA biosynthesis. Based on the optimal culture system using Rosetta(DE3), the yield of ALA achieved 3.8 g/l (29 mM) under the appropriate conditions in fermenter. PMID- 17333172 TI - Quantification of uncultured microorganisms by fluorescence microscopy and digital image analysis. AB - Traditional cultivation-based methods to quantify microbial abundance are not suitable for analyses of microbial communities in environmental or medical samples, which consist mainly of uncultured microorganisms. Recently, different cultivation-independent quantification approaches have been developed to overcome this problem. Some of these techniques use specific fluorescence markers, for example ribosomal ribonucleic acid targeted oligonucleotide probes, to label the respective target organisms. Subsequently, the detected cells are visualized by fluorescence microscopy and are quantified by direct visual cell counting or by digital image analysis. This article provides an overview of these methods and some of their applications with emphasis on (semi-)automated image analysis solutions. PMID- 17333174 TI - Influence of solubility-enhancing fusion proteins and organic solvents on the in vitro biocatalytic performance of the carotenoid cleavage dioxygenase AtCCD1 in a micellar reaction system. AB - The influence of the solubility-enhancing fusion proteins glutathione-S transferase (GST) and NusA on the heterologous expression and in vitro biocatalytic performance of the carotenoid cleavage dioxygenase AtCCD1 from Arabidopsis thaliana was investigated. A micellar dispersion of the water insoluble model substrate beta-apo-8'-carotenal in combination with Triton X-100 was used for the spectrophotometric in vitro assays. Specific activity in the cellular extract was twofold increased by the use of GST as a carrier protein, whereas it was decreased by 70% when fused with NusA. Reduced molar activity of the purified fusion proteins was observed, which could not be regained by proteolytic removal of the carrier protein. The addition of organic solvents in the form of short-chain aliphatic alcohols positively influenced the enzyme activity. Optimization of the reaction medium led to an 18-fold activation, and a clear correlation could be found between the organic solvent concentration required for maximum activation and the log P of the solvent. The results provide a foundation for the development towards the application of carotenoid cleavage dioxygenases as in vitro biocatalysts for the production of norisoprenoids and apocarotenals from carotenoids. PMID- 17333175 TI - Biotransformation of piceid in Polygonum cuspidatum to resveratrol by Aspergillus oryzae. AB - Biotransformation of piceid in Polygonum cuspidatum to resveratrol by Aspergillus oryzae was investigated in this study. Resveratrol is widely used in medicine, food, and cosmetic because of its pharmacological properties. However, it has a much lower content in plants compared with its glucoside piceid, which has a much lower bioavailability. Traditionally, the aglycone is acquired by acid or enzymatic hydrolysis of its glucoside, but the violent condition and the acid pollution in hydrolytic reaction and the high cost of the enzyme limit their industrial development. In this paper, fermentation of P. cuspidatum by A. oryzae was successfully performed, during which, piceid was converted to resveratrol with the highest yield of trans-resveratrol 1.35%, 3.6 times higher than that obtained from raw herb by microwave-assisted extraction. Scale-up production was also performed and the yield of trans-resveratrol was 3.1 times higher after 24 h incubation. Therefore, biotransformation is a better method to increase the yield of resveratrol because of its high yield and mild conditions. PMID- 17333176 TI - Biochemical and molecular characterization of a cellobiohydrolase from Trametes versicolor. AB - A cellobiohydrolase-encoding cDNA, Tvcel7a, from Trametes versicolor has been cloned and expressed in Aspergillus niger. The deduced amino acid sequence shows that Tvcel7a encodes a 456-amino acid polypeptide belonging to glycosyl hydrolase family 7. TvCel7a possesses a 19-amino acid secretion signal but does not possess a linker region nor a carbohydrate-binding domain. Two peaks of activity were obtained after TvCel7a was purified to apparent homogeneity by gel-filtration followed by anion-exchange chromatography. Mass spectrometry performed on the purified proteins confirmed that both peaks corresponded to the predicted sequence of the T. versicolor cellulase. The biochemical properties of the purified TvCel7a obtained from both peaks were studied in detail. The pH and temperature optima were 5.0 and 40 degrees C, respectively. The enzyme was stable over a pH range extending from pH 3.0 to 9.0 and at temperatures lower than 50 degrees C. The kinetic parameters with the substrate p-nitrophenyl beta-D: cellobioside (pNPC) were 0.58 mM and 1.0 micromol/min/mg protein for the purified TvCel7a found in both peaks 1 and 2. TvCel7a catalyzes the hydrolysis of pNPC, filter paper, beta-glucan, and avicel to varying extents, but no detectable hydrolysis was observed when using the substrates carboxymethylcellulose, laminarin and pNPG. PMID- 17333177 TI - The 68Ge/ 68Ga generator has high potential, but when can we use 68Ga-labelled tracers in clinical routine? PMID- 17333173 TI - Generation, annotation, and analysis of ESTs from four different Trichoderma strains grown under conditions related to biocontrol. AB - The functional genomics project "TrichoEST" was developed focused on different taxonomic groups of Trichoderma with biocontrol potential. Four cDNA libraries were constructed, using similar growth conditions, from four different Trichoderma strains: Trichoderma longibrachiatum T52, Trichoderma asperellum T53, Trichoderma virens T59, and Trichoderma sp. T78. In this study, we present the analysis of the 8,160 expressed sequence tags (ESTs) generated. Each EST library was independently assembled and 1,000-1,300 unique sequences were identified in each strain. First, we queried our collection of ESTs against the NCBI nonredundant database using the BLASTX algorithm. Moreover, using the Gene Ontology hierarchy, we performed the annotation of 40.9% of the unique sequences. Later, based on the EST abundance, we examined the highly expressed genes in the four strains. A hydrophobin was found as the gene expressed at the highest level in two of the strains, but we also found that other unique sequences similar to the HEX1, QID3, and NMT1 proteins were highly represented in at least two of the Trichoderma strains. PMID- 17333180 TI - Cellular therapy of cancer symposium December 2nd-3rd 2006 Manchester, UK. PMID- 17333179 TI - Accuracy of 3D acquisition mode for myocardial FDG PET studies using a BGO-based scanner. AB - PURPOSE: The aim of the present study was to evaluate the quantitative and qualitative accuracy of 3D PET acquisitions for myocardial FDG studies. METHODS: Phantom studies were performed with both a homogeneous and an inhomogeneous phantom. Activity profiles were generated along the phantoms using 2D and several 3D reconstructions, varying the 3D scaling value to adjust the scatter correction algorithm. Furthermore, ten patients underwent a dynamic myocardial FDG PET scan, using an interleaved protocol consisting of frames with alternating 2D and 3D acquisition. For each myocardial study, 13 volumes of interest were defined, representing 13 myocardial segments. First, the optimal scaling value for the scatter correction algorithm was determined using data from the phantom and four patient studies. This scaling value was then applied to all ten patients. 2D and 3D acquisitions were compared for both static (i.e. activity concentrations in the last 2D and 3D frames) and dynamic imaging (calculation of the metabolic rate of glucose). RESULTS: For both phantom and patient studies, suboptimal results were obtained when the default scaling value for the scatter correction algorithm was used. After adjusting the scaling value, for all ten myocardial FDG studies, a very good correlation (r2=0.99) was obtained between 2D and 3D data. With the present protocol no significant differences were observed in qualitative interpretation. CONCLUSION: The 3D FDG acquisition mode is accurate and has clear advantages over the 2D mode for myocardial FDG studies. A prerequisite is, however, optimisation of the 3D scatter correction algorithm. PMID- 17333178 TI - Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography. AB - PURPOSE: 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography ([18F]FLT PET) has been developed for imaging cell proliferation and findings correlate strongly with the Ki-67 labelling index in breast cancer. The aims of this pilot study were to define objective criteria for [18F]FLT response and to examine whether [18F]FLT-PET can be used to quantify early response of breast cancer to chemotherapy. METHODS: Seventeen discrete lesions in 13 patients with stage II-IV breast cancer were scanned prior to and at 1 week after treatment with combination 5-fluorouracil, epirubicin and cyclophosphamide (FEC) chemotherapy. The uptake at 90 min (SUV90) and irreversible trapping (Ki) of [18F]FLT were calculated for each tumour. The reproducibility of [18F]FLT-PET was determined in nine discrete lesions from eight patients who were scanned twice before chemotherapy. Clinical response was assessed at 60 days after commencing FEC. RESULTS: All tumours showed [18F]FLT uptake and this was reproducible in serial measurements (SD of mean % difference=10.5% and 15.1%, for SUV90 and Ki, respectively; test-retest correlation coefficient>or=0.97). Six patients had a significant clinical response (complete or partial) at day 60; these patients also had a significant reduction in [18F]FLT uptake at 1 week. Decreases in Ki and SUV90 at 1 week discriminated between clinical response and stable disease (p=0.022 for both parameters). In three patients with multiple lesions there was a mixed [18F]FLT response in primary tumours and metastases. [18F]FLT response generally preceded tumour size changes. CONCLUSION: [18F]FLT-PET can detect changes in breast cancer proliferation at 1 week after FEC chemotherapy. PMID- 17333181 TI - Induction of tumor-specific T-cell responses by vaccination with tumor lysate loaded dendritic cells in colorectal cancer patients with carcinoembryonic antigen positive tumors. AB - BACKGROUND: Dendritic cells (DCs) are the most effective antigen-presenting cells. In the last decade, the use of DCs for immunotherapy of cancer patients has been vastly increased. High endocytic capacity together with a unique capability of initiating primary T-cell responses have made DCs the most potent candidates for this purpose. Although DC vaccination occasionally leads to tumor regression, clinical efficacy, and immunogenicity of DCs in clinical trials has not been yet clarified. The present study evaluated the safety and effectiveness of tumor-lysate loaded DC vaccines in advanced colorectal cancer (CRC) patients with carcinoembryonic antigen (CEA) positive tumors. RESULTS: Six patients HLA A*0201-positive were vaccinated with autologous DCs loaded with tumor lysates (TL) together with tetanus toxoid antigen, hepatitis B, and influenza matrix peptides. Two additional patients were injected with DCs that were generated from their sibling or parent with one haplotype mismatch. All patients received the vaccines every 2 weeks, with a total of three intra-nodal injections per patient. The results indicated that DC vaccination was safe and well tolerated by the patients. Specific immune responses were detected and in some patients, transient stabilization or even reduction of CEA levels were observed. The injection of haplotype mismatched HLA-A*0201-positive DCs resulted in some enhancement of the anti-tumor response in vitro and led to stabilization/reduction of CEA levels in the serum, compared to the use of autologous DCs. CONCLUSION: Altogether, these results suggest that TL-pulsed DCs may be an effective vaccine method in CRC patients. Elimination of regulatory mechanisms as well as adjustment of the vaccination protocol may improve the efficacy of DC vaccination. PMID- 17333182 TI - Effectiveness of postural and instrumental reduction in the treatment of thoracolumbar vertebra fracture. AB - We compared the effectiveness of postural reduction and instrumental reduction in the treatment of thoracolumbar and lumbar vertebra fracture in 40 patients. Under general anaesthesia, postural reduction in a stretching prone position was first performed. Instrumental reduction and fixation were then conducted. Radiographs were made after each reduction. Comparisons between the two films and the fracture films were made based on the changes in prevertebral height of both the fractured vertebra and the adjacent superior and inferior intervertebral spaces. It was found that the recovery of the prevertebral height in postural and instrumental reductions was basically identical. The recovery of the prevertebral height in the intervertebral spaces was more significant in instrumental reduction. Both reductions were ineffective in patients whose compression of the diseased vertebra was more than two-thirds of the normal. In cases of lower lumbar vertebra fractures, the effect of both reductions was unsatisfactory. Our findings indicated that the effectiveness of the reduction of vertebra fracture depends on the quantitative change of the spongy bone of the injured vertebra. Instrumental reduction only exerts an indirect tension. Postural reduction is effective in reducing thoracolumbar vertebral fracture, while instrumental reduction exerts only a relatively weak effect but it is particularly useful to maintain the result of postural reduction. PMID- 17333183 TI - Paediatric forearm fractures: the increasing use of elastic stable intra medullary nails. AB - This paper entails a clinical review of outcomes and complications of 19 consecutive paediatric patients having undergone elastic stable intramedullary nailing for diaphyseal forearm fractures over a one year period. The mean age of patients was 9 years. The majority were male with a ratio of 17:2. In this group there were two patients with grade 1 open fractures. Four of the fractures required open reduction due to difficulty in reduction and soft tissue interposition. All fractures went on to osseous union with minimal deformity and full recovery. There were three complications which included one EPL rupture requiring delayed repair, one EPB partial rupture repaired at time of surgery, and one superficial radial nerve injury. Two patients also presented with nails penetrating the skin prior to removal. Elastic stable intramedullary nails offer good fixation to control deformity in midshaft forearm fractures for paediatric patients. However there is a high rate of possible complications around the radial insertion point. PMID- 17333185 TI - The mortality, morbidity and cost benefits of elective total knee arthroplasty in the nonagenarian population. AB - With the increasing life expectancy, a greater number of elderly patients are being referred to an orthopaedic department to have elective total knee arthroplasty (TKA). Total knee arthroplasty should be considered in the very elderly only after carefully balancing the benefits of surgery against the risks of surgery. The aim of this study was to analyse the mortality, morbidity and cost benefits of elective TKA in a cohort group of the nonagenarian population. Between 1990 and 2006, 42 patients >or=90 years of age had TKA surgery. Patient's notes were retrospectively analysed. A cost-benefit analysis was carried out by comparing the surgical costs against nursing home placement. The mean age at surgery was 90.4 years (range: 90-90.6). There was one major and 11 minor postoperative complications with no immediate or late postoperative deaths. The Knee Society Scores improved from 25 points (range: 8-44) to 81 points (range: 60 95), and the WOMAC Scores improved from 62 points (range: 54-73) to 41 points (range: 34-46) (p<0.002). The calculated cost-benefit savings for 42 patients at 5 years after TKA was estimated to be pound 2,746,839. Total knee arthroplasty in the nonagenarian population is safe, beneficial and cost-effective. PMID- 17333184 TI - Clinical examination versus ultrasonography in detecting developmental dysplasia of the hip. AB - Although hip ultrasonography is gaining acceptance as the most effective method for the early diagnosis of developmental dysplasia of the hip, there is still some controversy regarding the use of ultrasonography as a screening method. The purpose of this study was to investigate prospectively the capacity of clinical examination findings and associated risk factors to detect developmental dysplasia of the hip defined ultrasonographically in infants. A total of 3,541 infants underwent clinical examination and hip ultrasonography. Measured against ultrasonography as a standard, the sensitivity and specificity of clinical examination were 97% and 13.68%, respectively. Graf type IIb or more severe developmental dysplasia was found in 167 infants (208 hips), at an overall frequency of 4.71%. Graf type IIa physiological immaturity was encountered in 838 hips, and of these, 15 hips (1.78%) developed Graf type IIb dysplasia and underwent treatment. Patient characteristics that were found to be significant risk factors were swaddling use, female gender, breech delivery and positive family history. Given its low specificity, our findings suggest that clinical examination does not reliably detect ultrasonographically defined developmental dysplasia of the hip in infants being screened for this disease. PMID- 17333187 TI - Profuse erythema multiforme induced by chlorambucil. PMID- 17333186 TI - Functional outcome after lengthening with and without deformity correction in polio patients. AB - Poliomyelitis is one of the causes of limb length discrepancy. The aim of lengthening and deformity correction in such patients is to improve the functional mobility of the patient. This study aims to find out whether or not improvement of limb length inequality with or without deformity correction affects or improves ambulation. This prospective study included 32 skeletally mature patients managed using the Ilizarov technique and external fixation for limb lengthening with or without deformity correction. Functional Mobility Scale scoring was used for assessment of ambulation before lengthening and at the final follow-up. The average duration of follow-up was 2 years and 9 months. Lengthening alone did not change the Functional Mobility Scale score. While lengthening associated with deformity correction improved the mobility scale at 5 m only (in the house), it had no effect on the 50 and 500 m score. PMID- 17333188 TI - Zinc protoporphyrin, a useful parameter to address hyperferritinemia. AB - Zinc protoporphyrin (ZPP) is produced instead of heme as soon as iron support to erythropoiesis becomes insufficient. In iron deficiency the intra-erythrocytic ZPP concentration is increased. The aim of this study was to investigate whether ZPP is influenced by increased iron levels in hereditary hemochromatosis (HE) and is useful in the clarification of hyperferritinemia. Twenty HE patients and 160 patients with hyperferritinemic caused by anemia of chronic disorders, liver diseases, transfusional iron overload and hematologic or solid malignancies were enrolled. ZPP was measured using the Aviv front-face hematofluorometer (normal 1.0. RESULTS: Imexon was synergistic when combined with DNA-binding agents (cisplatin, dacarbazine, melphalan) and pyrimidine-based antimetabolites (cytarabine, fluorouracil, gemcitabine) in both cell lines. Antagonistic combinations with imexon included methotrexate and the topoisomerase I (TOPO I) and II (TOPO II) inhibitors irinotecan, doxorubicin, mitoxantrone and etoposide. Docetaxel was synergistic with imexon in both cell lines whereas paclitaxel and fludarabine showed a mixed result. Dexamethasone and the proteasome inhibitor bortezomib showed synergy in myeloma cells and additivity in the melanoma cells. The vinca alkaloid, vinorelbine, and the multi-targeted antifol, pemetrexed, were additive with imexon in both cell lines. DISCUSSION: The consistent synergy seen for imexon and alkylating agents may relate to the sulfhydryl-lowering effect of imexon, which would render cells more sensitive to electrophilic species from the alkylators. The marked synergy noted with pyrimidine-based antimetabolites was unexpected and may relate to the induction of cell cycle arrest in S-phase. The strong antagonism noted for imexon with topoisomerase I and II inhibitors may be due to the effect of imexon at increasing oxidant levels which are known to antagonize the cytotoxic effects of topoisomerase poisons. In contrast, the synergy seen with bortezomib in myeloma cells may be related to an increase in reactive oxygen species (ROS) from both drugs. These results suggest that combinations of imexon with alkylating agents and pyrimidine-based antimetabolites are rational to pursue in therapeutic studies in vivo. PMID- 17333196 TI - A single intravenous dose of prednisolone induces phosphatidylserine externalization, loss of surface marker expression and a 24-h net increase in human peripheral blood lymphocytes ex vivo. AB - To understand how corticosteroids act; a characterization of their effects on lymphocytes is necessary. The effect of in vivo corticosteroids on lymphocyte subpopulations, their surface molecules and externalization of phosphatidylserine (apoptosis) is examined. In a crossover study, a single, intravenous dose of 2 mg/kg prednisolone or saline was given to six male adult human volunteers. Blood samples were withdrawn before and 30 min, 2, 5, 23 and 29 h thereafter. Lymphocyte subsets were determined by FACS analysis. Externalization of phosphatidylserine was measured by Annexin-V; cell fragments were excluded by propidium iodide staining. Lymphocyte number decreased from 2,007 +/- 473 to 634 +/- 119 microl after 5 h and rose to 3,112 +/- 436 microl after 23 h. CD4, CD8 and B cell counts declined significantly after 5 h (P < or = 0.01). The expression of CD28 or CD95 on T cells and the natural killer cells were unaffected. There was a significant rebound of lymphocyte numbers above baseline 23 h after prednisolone. At baseline 9.9 +/- 3.8% of cells in the lymphocyte gate did not stain for CD3, CD20 or CD56 (referred to as "null cells"). 5 h after application of prednisolone, there was a significant increase of "null cells" (28 +/- 12%, P = 0.018). The percentage of phosphatidylserine positive CD4 cells rose from 8.1 +/- 3.3 to 19.8 +/- 8% after intravenous prednisolone, while the percentage of phosphatidylserine positive CD8, B and NK cells remained largely unchanged. Prednisolone induces a most significant depletion of CD4 cells, which to some degree is associated with apoptosis. The net increase of lymphocyte numbers 23 h after prednisolone application may be a beneficial late effect of a single i.v. prednisolone shot. PMID- 17333198 TI - Utility of multi-detector CT for pre-operative diagnosis of internal hernia through a defect in the broad ligament (2007: 1b). AB - Internal hernia through a defect in the broad ligament is a rare cause of intestinal obstruction, and pre-operative diagnosis is generally difficult. Here, we report our experience in which multi-detector computed tomography (MDCT), which allows direct recognition of incarcerated small bowel, was useful in the pre-operative diagnosis of this hernia. PMID- 17333199 TI - Basic principles of anatomy for optimal surgical treatment of prostate cancer. AB - The treatment of prostate cancer (PCa) with nerve sparing radical prostatectomy (NSRP) has experienced a substantial improvement in recent years due to new insights in anatomy of the prostate and of the adjacent structures. Knowledge of this specific anatomy is mandatory during RP in order to avoid injuries to functional tissue. Above all, these tissues are the neurovascular bundle (NVB) and the urethral sphincter. We therefore reviewed the available literature on prostatic anatomy and summarized it in this article. A search of the PubMed database was performed using the keywords radical prostatectomy, anatomy, neurovascular bundle, fascia, pelvis and sphincter. Relevant articles were reviewed, analyzed and summarized. This article gives an insight in the anatomy of the NVB, the urethral sphincter and the fascias surrounding the prostate. The NVB might be hampered near the seminal vesicles, at the lateral surface of the prostate and in the area of the prostato-urethral junction. The urethral sphincter might be hampered during dissection of the dorsal vein complex and during dissection of the urethra at the prostatic apex. Finally, the anatomy of the fascias surrounding the prostate is complex and can inter-individually vary substantially, which adds to the technical difficulties of NSRP. With this article we provide an overview on the complex anatomy of the prostate and the adjacent tissues. Respecting and considering these anatomic principles during NSRP should result in good postoperative functional outcome, as well as in good outcome in cancer control. PMID- 17333200 TI - Optimal treatment of locally advanced prostate cancer. AB - The treatment of clinically locally advanced prostate cancer (cT3-4) is subject to controversies. Patients with lymph node metastases as well as patients with overstaged localized and thus curable disease fall into this category. Radical prostatectomy, external beam radiotherapy and early or deferred hormonal therapy are possible treatment options. Multimodal treatment (i.e., a combination of these options) is frequently used. After radical prostatectomy, Gleason score adjusted disease-specific survival does not differ meaningfully between the tumor stages pT2 and pT3-4. In the case of lymph node metastases after radical prostatectomy, but not in node-negative disease, adjuvant hormonal treatment seems to improve survival. Adjuvant radiotherapy may improve biochemical and local control in locally advanced prostate cancer, a survival benefit has, however, not yet been proven. External beam radiotherapy alone provides unfavourable survival rates in locally advanced prostate cancer. Adjuvant hormonal treatment may improve outcome in this setting. When no curative treatment is chosen, early hormonal treatment seems to provide modest benefit compared with deferred therapy. PMID- 17333201 TI - Steroid- and calcineurin inhibitor free immunosuppression in kidney transplantation: state of the art and future developments. AB - Owing to the increasing disparity of organ demand and organ supply the search for optimal immunosuppressive strategies has become a central issue in kidney transplantation (KTX). In the focus today are modifications of the use of calcineurin-inhibitors (CNIs, Cyclosporine A/Tacrolimus) and steroids, as they are nephrotoxic and promote cardiovascular risk factors like arterial hypertension, hyperlipidemia and diabetes mellitus. These modifications can either be withdrawal or avoidance of these substances in combination with new and/or established immunosuppressants. Because about half of all KTXs are performed by or with the help of urologists' knowledge of modern immunosuppressive regimens is crucial also for urologists. We performed a literature research (PubMed, DIMDI, medline) for CNI- and steroid-sparing protocols and studies to elucidate their influence on graft-function and graft- and patient-survival. New substances and actual studies were also evaluated. Several published reports on CNI- and steroid-sparing protocols after KTX exist, including withdrawal, reduction or avoidance. The time of reduction seems to be crucial: an initially increased immune response should be counterbalanced by an initially intensified immunosuppression. Therefore, late steroid withdrawal seems to be safer than early withdrawal especially in Cyclosporine-based immunosuppression. Steroid avoidance also seems feasible on a CNI based regimen, especially in context with induction therapy. Withdrawal or avoidance of CNIs seems feasible with mycophenolate acid and/or induction therapy with IL 2 receptor antibodies as co-immunosuppressants. This is of interest in grafts with deteriorating function or from donors with extended criteria. Also, CNI- and steroid-free immunosuppression can be successfully performed with new immunosuppressants but results are yet premature. CNI- and/or steroid reduction, withdrawal or even avoidance is feasible. As long-term graft function is the goal of KTX and as more kidneys from donors with extended criteria are transplanted "tailored immunosuppression" will replace standards in the future. PMID- 17333202 TI - Therapy of recurrent disease after radical prostatectomy in 2007. AB - Recurrence rates of 20-40% after prostatectomy are described. This review will discuss curative treatment options for salvage after primary therapy. Relevant information was identified through searches of published studies, abstracts from scientific meetings, and review articles. Clinical experience in salvage therapy is limited. Conformal radiotherapy to the prostatic bed for PSA relapse and biopsy proven local recurrences after prostatectomy remains the only potentially curative therapy. It can provide durable biochemical control in a range from 17 to 78%. Salvage radiotherapy is well tolerated. Some prognostic factors exist which can help to select the right patient for this treatment. Patients have to be treated early for PSA relapse. Conformal radiotherapy to the prostatic bed for PSA relapse and biopsy proven local recurrences after prostatectomy is a good documented curative therapy. In a patient with a high probability of local recurrence early radiotherapy for PSA relapse is suggested. PMID- 17333203 TI - Role of nomograms for prostate cancer in 2007. AB - Nomograms have been developed to predict prostate cancer (PCa) related outcomes. We report what has been achieved and what can be expected in 2007 and in the future. We reviewed the literature to provide guidelines in terms of criteria, limitations and clinical value of nomograms in 2007. Further, we report a set of recent PCa nomograms, where certain criteria are listed which were used to develop each nomogram. Our findings suggest a demand for an update of nomograms as well as head-to-head comparisons to determine the best-suited model in select fields of PCa outcomes. In 2007 and the future, an increasing number of nomograms will address important endpoints such as PSA recurrence, local and distant metastases, or androgen-independent PCa-specific survival. Our results suggest that nomograms represent valid risk stratification models to achieve most accurate predictions. In 2007 and the future, more specific and refined nomograms will be available which address relevant clinical end points. Moreover, novel markers in PCa outcomes will be quantified using the nomogram approach. PMID- 17333204 TI - Clinical study on the effect of mineral waters containing bicarbonate on the risk of urinary stone formation in patients with multiple episodes of CaOx urolithiasis. AB - Investigations in healthy persons have shown that drinking mineral water containing HCO(3) has a positive effect on urine supersaturated with calcium oxalate (SS(CaOx)). The present study evaluates in a common setting whether these effects are also relevant in patients with multiepisodic urinary stone formation. A total of 34 patients with evident multiepisodic CaOx-urolithiasis were included in the study. Patients with hyperparathyroidism, renal tubular acidosis, Wilson's disease, Cushing disease, osteoporosis and malignant diseases were excluded. In a cross-over design and double-blinded the patients received 1.5 l of a mineral water with 2.673 mg HCO(3)/l (test water) or the same amount of water with a low mineral content (98 mg HCO(3)/l) (control water) daily for 3 days. During the study period the patients diet was recorded in a protocol, but not standardised. The main target parameter was SS(CaOx )in 24 h urine. In addition, urinary pH and the most important inhibiting and promoting factors were measured in 24 h urine (Ca, Ox, Mg, Cit). Both waters tested led to a highly significant increase in 24 h urine volume without a difference between each other. In the group, drinking the water containing HCO(3) the urinary pH increased significantly and was within a range relevant for metaphylaxis of calcium oxalate stone formation (x=6.73). This change was highly significant compared to the control group. In addition, significantly increased magnesium and citrate concentration were also observed. Supersaturation with calcium oxalate decreased significantly and to a relevant extent; however, there was no difference between the waters tested. As expected, the risk of uric acid precipitation also decreased significantly under bicarbonate water intake. However, an increase of the risk of calcium phosphate stone formation was observed. It is evident that both waters tested are able to lower significantly and to a relevant extent the risk of urinary stone formation in patients with multiepisodic CaOx-urolithiasis. In addition, the bicarbonate water increases the inhibitory factors citrate and magnesium due to its content of HCO(3) and Mg. Thus, it can be recommended for metaphylaxis of calcium oxalate and uric acid urinary stones. PMID- 17333207 TI - Photoreceptor spectral sensitivity in island and mainland populations of the bumblebee, Bombus terrestris. AB - Most species of flower-visiting Hymenoptera are trichromatic, with photoreceptor spectral sensitivity peaks in the UV, blue and green regions of the spectrum. Red flowers, therefore, should be relatively difficult to detect for such insects. Nevertheless, in population biological studies in the bumblebee, Bombus terrestris, the Sardinian island population (B. t. sassaricus) displayed significantly higher responses to red artificial flowers (in tests of innate colour choice and detectability) than several mainland populations of the same species (Chittka et al. in Cognitive ecology of pollination, pp 106-126, 2001; Popul Ecol 46:243-251, 2004). Since there is relatively little physiological data on population differences in sensory systems, we used intracellular recording to compare photoreceptor spectral sensitivity in B. t. sassaricus and the southern European and Mediterranean population, B. t. dalmatinus. The results show both populations to be UV-blue-green trichromats, but with a small but significant increase in long-wave sensitivity in island bees. Spectral peaks were estimated at 348, 435 and 533 nm (B. t. dalmatinus) and 347, 436 and 538 nm (B. t. sassaricus) for UV, blue and green receptors, respectively. There were no significant differences in UV and blue receptor sensitivities. We found no photoreceptors maximally sensitive to red spectral light in the Sardinian population and model calculations indicate that the behavioural population differences in colour responses cannot be directly explained by receptor population differences. PMID- 17333206 TI - Characterisation of a blowfly male-specific neuron using behaviourally generated visual stimuli. AB - The pursuit system controlling chasing behaviour in male blowflies has to cope with extremely fast and dynamically changing visual input. An identified male specific visual neuron called Male Lobula Giant 1 (MLG1) is presumably one major element of this pursuit system. Previous behavioural and modelling analyses have indicated that angular target size, retinal target position and target velocity are relevant input variables of the pursuit system. To investigate whether MLG1 specifically represents any of these visual parameters we obtained in vivo intracellular recordings while replaying optical stimuli that simulate the visual signals received by a male fly during chasing manoeuvres. On the basis of these naturalistic stimuli we find that MLG1 shows distinct direction sensitivity and is depolarised if the target motion contains an upward component. The responses of MLG1 are jointly determined by the retinal position, the speed and direction, and the duration of target motimotion. Coherence analysis reveals that although retinal target size and position are in some way inherent in the responses of MLG1, we find no confirmation of the hypothesis that MLG1 encodes any of these parameters exclusively. PMID- 17333205 TI - Assay-specific artificial neural networks for five different PSA assays and populations with PSA 2-10 ng/ml in 4,480 men. AB - Use of percent free PSA (%fPSA) and artificial neural networks (ANNs) can eliminate unnecessary prostate biopsies. In a total of 4,480 patients from five centers with PSA concentrations in the range of 2-10 ng/ml an IMMULITE PSA-based ANN (iANN) was compared with other PSA assay-adapted ANNs (nANNs) to investigate the impact of different PSA assays. ANN data were generated with PSA, fPSA (assays from Abbott, Beckman, DPC, Roche or Wallac), age, prostate volume, and DRE status. In 15 different ROC analyses, the area under the curve (AUC) in the PSA ranges 2-4, 2-10, and 4-10 ng/ml for the nANN was always significantly larger than the AUC for %fPSA or PSA. The nANN and logistic regression models mostly also performed better than the iANN. Therefore, for each patient population, PSA assay-specific ANNs should be used to optimize the ANN outcome in order to reduce the number of unnecessary biopsies. PMID- 17333208 TI - Effects of diet quality on phenotypic flexibility of organ size and digestive function in Mongolian gerbils (Meriones unguiculatus). AB - In the context of evolution and ecology, there is a trade-off between the benefits of processing food through a digestive system with specific phenotypic attributes and the cost of maintaining and carrying the digestive system. In this study, we tested the hypothesis that digestive modulations at several levels can match each other to meet the energy and nutrient demands of Mongolian gerbils, a small granivorous rodent species, by acclimating them to a high-quality diet diluted with alfalfa powder. Mongolian gerbils on the diluted diet maintained metabolizable energy intake by an integrated processing response (IPR), which included increases in dry matter intake, gut capacity and rate of digesta passage after 2-weeks of acclimation. Down-regulation of hydrolytic enzyme activity in the intestinal brush-border membrane supported the adaptive modulation hypothesis. The absence of up-modulation of summed enzyme hydrolytic capacity on the diluted diet indicated that greater mass of small intestine on a high-fibre diet is not a direct indicator of digestive or absorptive capacity. Changes in mass of vital organs and carcass suggested that the amount of energy allocated to various organs and hence physiological functions was regulated in response to diet shift. PMID- 17333209 TI - Salvaging the "lost peritoneum" after ventriculoatrial shunt failures. AB - OBJECTIVE: Placement of a ventriculoperitoneal (VP) shunt is the long-standing treatment of choice for hydrocephalus. However, in many patients with repeated distal failures, ventriculoatrial (VA) shunts are placed. Should the VA shunt fail, finding appropriate distal sites is often difficult. MATERIALS AND METHODS: We identified six patients, over a 3-year period, in whom conversion of VA to VP shunt was successfully performed with the aid of diagnostic laparoscopy or laparotomy. There were no ensuing shunt failures during the follow-up period (mean 1.5 years). CONCLUSION: Because of the benefits of VP over VA shunting, every effort should be made to preserve the peritoneum as the target for the distal catheter. Laparotomy/laparoscopy is useful in locating suitable peritoneal targets when converting to VP shunt after VA shunt failure, or as a final effort before VA shunt conversion. PMID- 17333210 TI - Glicentin inhibits internalization of enteric bacteria by cultured INT-407 enterocytes. AB - Glicentin, the main component of enteroglucagon, has trophic effects on intestinal mucosa. It may also have an inhibitory effect on extraintestinal invasion of enteric bacteria. We have established an in vitro bioassay system for determining the effects of recombinant human glicentin on bacterial internalization by confluent enterocytes. An INT-407 cell line was serum-deprived for 2 days and was then treated on transwell filters for 24 h with a medium containing one of the following: glicentin 100 ng-1 microg/ml, glucagons-like peptide-2 (GLP-2) 1 microg/ml, 10% fetal bovine serum (FCS), or without any growth factors. Pure cultures of Salmonella enteritidis, Escherichia coli, and Enterococcus faecalis were introduced to the upper chambers of the filter units. Following 2 h of incubation the numbers of bacteria in the lower chambers were measured. Pretreatment of enterocytes with glicentin inhibited bacterial internalization compared to untreated or GLP-2 enterocytes. Glicentin was associated with inhibition of enterocyte internalization of enteric bacteria by a mechanism that might be related to the integrity of the enterocyte adhesive junctions and tight junctions and to the production of sIgA. Glicentin seems to have a function as a barrier-sustaining agent that inhibits extraintestinal invasion of enteric bacteria. PMID- 17333211 TI - Late abscess formation following indirect hernia repair utilizing silk suture. AB - Inguinal hernia repair is the most common operation performed by pediatric surgeons. The critical portion of the operation is high ligation of the hernia sac, which is classically performed with silk suture. This foreign body has the potential to serve as a nidus for latent infection/rejection that may result in an abscess long after the operation. This complication has rarely been described in the literature. We have cared for six children who have presented with latent inguinal or pelvic abscesses following high ligation of the inguinal hernia sac with silk suture. The purpose of this report is to examine the varied presentations by which latent complications following herniorraphy may manifest. The pediatric surgeon should recognize that not every inguinal mass following a previous inguinal herniorraphy represents a recurrent hernia! A retrospective review of the charts of six patients with late abscess formation following antecedent inguinal hernia repair was undertaken. The details of the initial and operative endeavors were recorded with specific attention to the details of the initial operative hernia repair as well as the suture material utilized. Inguinal hernia repair continues to be the most common operation performed by pediatric surgeons. Utilization of braided, non-absorbable silk suture may result in latent abscess formation and the need for operative drainage of inguinal or pelvic abscess. Today, as other types of suture material are likely equally efficacious in the ability to effectively close the patent processus vaginalis, pediatric surgeons should consider utilizing non-braided, or absorbable suture material for high ligation of the indirect hernia sac to potentially prevent this complication. PMID- 17333212 TI - Clitoroplasty: past, present and future. AB - This paper reviews the history of clitoral surgery throughout the twentieth century. The changing operations, from amputation through to attempts to produce a normal clitoris mirror the changing attitudes and available knowledge. It also examines the current issues that arise out of available data on long-term outcomes of clitoroplasty. PMID- 17333213 TI - Exogenous calcitonin gene-related peptide perturbs the direction and length of gubernaculum in capsaicin-treated rats. AB - Calcitonin gene-related peptide (CGRP) released from the genitofemoral nerve (GFN) is proposed to control gubernacular migration to the scrotum during inguinoscrotal descent. As previous studies suggested that both CGRP and androgens are necessary to stimulate gubernacular elongation and proliferation, this study aimed to test whether CGRP perturbed growth of the gubernaculum by exogenous injection in a rat model of GFN blockade with an intact androgen pathway. Sprague-Dawley rats (day 0, n = 34) were injected with capsaicin (sensory neurotixin) or vehicle. CGRP (25 microl of 2 x 10 5 molar concentration) Or castor oil was administered at the umbilicus 24 h later, then every other day thereafter for 10 days. Groups of rats were sacrified on days 8 and 28, and the tip of the gubernaculunx was identified in relation to the scrotum and umbilicus. The length of the processus vaginalis (PV) was measured. In group 1 (capsaicin and CGRP), at 8 days of age (n = 8) the testes were found in the intraabdominal or suprainguinal position in 87.5% (14 testes) and the tip of the gubernaculum was oriented more laterally than normal. However the mean PV length was 5.1 mm, which was shorter than control groups (9-10.8 mm) (P < 0.001, t-test). On the other hand, at day 28, the testes were located proximal to the internal inguinal ring in 66.7% (8 testes) with their gubernacular tip oriented in part towards the umbilicus. The mean of the PV length was 12.2 mm, which was significantly decreased compared to other groups (P < 0.001, t-test). In group 2 (capsaicin and castor oil) and group 3 (vehicle and CGRP) the testes of one rat in each group at 28 days of age were located in the abdomen at the internal inguinal ring with the distal gubernacular attachment lying free and directed caudally towards the scrotum, while the rest of the testes were found in the normal location. These findings suggest that chemical interruption of sensory nerves followed by CGRP injections in rats can perturb gubernacular growth and can change the direction of migration. PMID- 17333214 TI - Mature and immature teratomas: results of the first paediatric Italian study. AB - Teratoma is the most common germ cell tumour in childhood; mature (MT) and immature teratomas (IT) are benign tumours, but if they recur, they can be in some cases malignant. The aim of this paper is to evaluate Italian patients with MT and IT enrolled from 1991 to 2001, in a prospective multicentric study. One hundred and eighty-three patients, observed in 15 Italian Centers of Paediatric Oncology and three Paediatric Surgical Units were enrolled. Clinical data, treatment and results were all analysed. Initial evaluation and subsequent follow up included clinical examination, tumour markers and imaging procedures. Surgical resection was recommended for all the tumours. Histology was centrally reviewed and IT was classified as grading 1-3. Chemotherapy (CT) with Vinblastine, D: actinomycin and cyclophosphamide was indicated for extra-testicular IT grade 2 or 3. MT was diagnosed in 127 patients (93 F and 34 M, age 1-192 months, median 24): 58 patients had gonadic tumour (23 testicular, 35 ovaric), 69 extragonadic (45 sacrococcygeal, 11 mediastinic, 7 retroperitoneal, 6 in other sites). A complete resection was performed in 117 patients, a partial resection in eight patients and biopsy in one. IT was diagnosed in 56 patients (34 F, 22 M, age 1-168 months, median 7). The T grading was 1 in 14 cases, 2 in 26, 3 in 16; 28 had gonadic T (17 ovary, 11 testis), 28 extragonadic (sacrococcygeal 19, mediastinic 3, retroperitoneal 2, other sites 4). CT was administered in eight patients; 15/182 patients relapsed (1 in a metastatic site) and in 5/15 the relapse showed malignant histology. Seven MT (5.5%) relapsed (five sacrococcygeal, one retroperitoneal, one mediastinic): surgery at diagnosis had been complete in five and with residual in two; the relapse was malignant in two patients with sacrococcygeal (sc) tumours, who had a complete resection and a partial resection respectively. Eight IT (14.2%) relapsed (four ovary, three sc, one retroperitoneal). The initial surgical resection had been complete in one, with residual in six, and a biopsy had been performed in one. A malignant recurrence occurred in two patients with sc tumours (after partial resection in one and after biopsy + CT in one) and in one patient with ovarian IT after a partial resection. All the patients underwent surgical excision of the recurred mass; CT according to Protocol for Malignant GCT was administered to those who had malignant recurrence; 122/126 patients with MT and 53/56 with IT are alive without disease with a follow up of 8-144 months (median 56). Two patients with malignant relapse (one with sc MT, one with sc IT) died because of the progression of the disease. Another two died due to severe malformations (one MT, one IT) and three were lost to follow up (two MT, one IT). The overall survival (OS) at 10 years is 98% (95% CI 93.9-99.4); the event free survival (EFS) is 90.4% (95 CI 84.8-94.0). At Cox analysis no significant difference in EFS was found regarding age and site of the primary tumour, while females (P = 0.011), patients with grade 1-3 histology (P = 0.025) and patients with incomplete resection appeared at higher risk of death or relapse (P < 0.001), with a seven, three and eightfold increase in risk, respectively. Our data showed that incomplete resection and female gender are important risk factors for relapse or death, more so than IT histology. The number of patients treated with CT is not sufficient to evaluate the efficacy of CT in avoiding malignant relapse. PMID- 17333215 TI - Renal cell carcinoma in children under 10 years old: a presentation of four cases. AB - Renal cell carcinoma (RCC) in childhood is a unique disease entity, representing only 2.3-6.6% of all renal tumors in children. Most experience with pediatric RCC is limited to case reports or case series consisting of relatively small numbers of cases. The aim of this study is to present four additional cases of this unique disease entity. The records of four patients presenting to our institution with renal cell carcinoma between 1986 and 2006 were examined. Only patients younger than 10 years were included. The clinical data included age, sex, signs and symptoms, surgery performed and clinical outcome. Data recorded from the pathology reports included tumor size, histologic subtype, grade (WHO), and stage (TNM). There were three boys and one girl aged between 11 months and 10 years at presentation. The classic triad of flank pain, gross hematuria and palpable abdominal mass were not encountered. A histopathological diagnosis of RCC was confirmed in all four cases without any positive lymph node involvement. Due to the increased detection of tumors with the use of imaging techniques such as ultrasound and computerized tomography, an increased number of incidentally diagnosed RCCs are found. The primary choice of the treatment of any stage of RCC is surgical excision. However, the preoperative diagnosis of tumor in children is difficult and the effects of chemotherapy, including immunotherapy, are unclear. PMID- 17333216 TI - Local and systemic impact of pneumoperitoneum on prepuberal rats. AB - Pneumoperitoneum (PN) and the gas used to insufflate the abdominal cavity during laparoscopy seem to be responsible for local and systemic modifications. The aim of this study was to verify the effects of intra-abdominal carbon dioxide (CO(2)) and air insufflation on the peritoneum, as well as the cortico-surrenal response in prepuberal rats. Sixty prepuberal rats were divided into three groups: in the first (S, n = 36), PN was induced with CO(2), whereas in the second (A, n = 14), it was induced with filtered room air; in both conditions, insufflation lasted 30 min at a pressure of 10-12 mmHg. The third group (C, n = 10), underwent general anesthesia only. Two hours after inducing anaesthesia, 12 rats in group S, 6 in group A and 6 in group C were killed and the remaining, after 24 h; specimens of the visceral and the parietal peritoneum were obtained for histological examination, blood sample was taken for cortisol and DHEA-S assays at the different study periods. At the histological examination performed 2 h later, the groups S and A presented inflammatory cell infiltrate in the parietal and visceral peritoneum; this finding was even more marked in group A, which presented also congestion, hemorrhage and disruption of the cell line. Twenty four hours after the experiment, the peritoneum of the two insufflated groups presented chronic infiltrate and reactive mesothelial cells with congestion, which was more evident in group A, but totally absent in group C. Cortisol levels were significantly higher in groups S and A (2.15:1 ratio) killed 2 h later compared to those killed 24 h later and to the control group. DHEA-S levels were not significantly different between the groups. Our results demonstrate that the chemical, physical and molecular impact of CO(2) on the peritoneum causes inflammation and tissue damage, this was even more evident 24 h after our experiment and in the air insufflated group. PN induced a significant variation in blood cortisol levels at 2 h. The CO(2) insufflation should be limited in patients with pre-existing peritoneal damage. PMID- 17333218 TI - Apocrine carcinoma of the anogenital region. A case report including immunohistochemical and molecular study, discussion of differential diagnosis and a review of the literature. PMID- 17333217 TI - Lack of association of the 3'-UTR polymorphism in the NFKBIA gene with Crohn's disease in an Israeli cohort. AB - BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract associated with dysregulation of the immune response. It is caused by a combination of environmental and genetic factors. Patients with CD have a TH1-type inflammatory response characterized by nuclear factor kappa B (NFkappaB) activation. Mutations in the bacterial pattern recognition receptors NOD2/CARD15 and Toll-like receptor 4 (TLR4) genes, which lead to activation of NFkappaB under normal circumstances, have been associated with increased susceptibility for CD. NFkappaB plays a critical role in the immune response and is down-regulated by NFkappaB inhibitor alpha (NFKBIA). NFKBIA was found to be a susceptibility gene for German CD patients lacking NOD2/CARD15 mutations. MATERIALS AND METHODS: A cohort of 231 Israeli CD patients previously genotyped for the single nucleotide polymorphisms (SNPs) in the CARD15, TLR4 susceptibility genes for CD, was analyzed for the 3'-untranslated region (UTR) SNP of the NFKBIA gene in comparison to 100 healthy ethnically matched controls. We evaluated the contribution of the 3'-UTR SNP in NFKBIA in patients with or without other SNPs in CARD15 to age of onset, disease location, and disease behavior (Vienna classification). RESULTS: We did not identify a significant difference in allele and genotype frequencies between either groups or an effect on phenotype. No interactions were found between NFKBIA and any NOD2. CONCLUSIONS: The contribution of population diversity to susceptibility genes for CD plays an important role in disease-associated variants and is important for better understanding of the pathologic mechanisms of the polymorphism. PMID- 17333219 TI - A novel MSH2 mutation in a Chinese family with hereditary non-polyposis colorectal cancer. AB - BACKGROUND AND AIMS: Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary colon cancer syndrome accounting for 1-5% of all colorectal cancer cases. Germline mutations in DNA mismatch repair (MMR) genes are associated with the clinical phenotype of HNPCC. Defects in the MSH2 gene may account for about 40% of HNPCC cases including nucleotide substitutions, deletions and insertions. Only a few mutations were reported in Chinese families. This study was performed to identify the disease-causing gene mutation(s) and conduct pre-symptomatic diagnosis in a Chinese family with HNPCC. MATERIALS AND METHODS: Mutation analysis in MLH1 and MSH2 followed by pre-symptomatic diagnosis in MSH2 was performed on genomic DNA isolated from the family members. RESULTS: A novel duplication mutation of four nucleotides in exon 7 of MSH2 (MSH2: c.1216_1219dupCGAC) resulting in a premature stop 10 codons downstream in MSH2 (p.L407fsX417) was found. The mutation was associated with HNPCC and an asymptomatic carrier was found in the family. CONCLUSION: HNPCC in a Chinese family is associated with a novel mutation in the MSH2 gene (MSH2: c.1216_1219dupCGAC). PMID- 17333220 TI - TDP-43 immunoreactivity in neuronal inclusions in familial amyotrophic lateral sclerosis with or without SOD1 gene mutation. AB - Recently, 43-kDa TAR DNA-binding protein (TDP-43) was identified as a component of ubiquitinated inclusions (UIs) in sporadic amyotrophic lateral sclerosis (SALS). To clarify whether TDP-43 immunoreactivity is present in neuronal inclusions in familial ALS (FALS), we examined immunohistochemically the brains and spinal cords from four cases of FALS, two with Cu/Zn superoxide dismutase (SOD1) gene mutation and two without, together with three cases of SALS and three control subjects, using two antibodies, one polyclonal and one monoclonal, against TDP-43. Neuropathologically, the SOD1-related FALS cases were characterized by Lewy body-like hyaline inclusions (LBHIs) in the lower motor neurons. On the other hand, the SOD1-unrelated FALS cases showed degeneration restricted to the upper and lower motor neuron systems, with Bunina bodies (BBs) and UIs in the lower motor neurons, being indistinguishable from SALS. No cytoplasmic TDP-43 immunoreactivity was observed in the control subjects or SOD1 related FALS cases; LBHIs were ubiquitinated, but negative for TDP-43. UIs observed in the SALS and SOD1-unrelated FALS cases were clearly positive for TDP 43. BBs were negative for this protein. Interestingly, in these SALS and FALS cases, glial cells were also found to have cytoplasmic TDP-43-positive inclusions. These findings indicate that the histological and molecular pathology of SALS can occur as a phenotype of FALS without SOD1 mutation. PMID- 17333221 TI - Lateral approach for fixation of the fractures of the distal tibia. Outcome of 20 patients. Technical note. AB - INTRODUCTION: The treatment of fractures of the distal third of the tibia remains still controversial. It is often difficult to get and retain good reduction by non-operative or nailing methods. Open reduction and plate fixation offers good reduction and retention of the achieved position. However, increased soft tissue damage and high complication rate has led to search less invasive surgical methods such as minimal invasive plating technique. MATERIAL AND METHODS: Lateral approach for the distal tibia allows to reduce and to plate both the fibula and the tibia using only one skin incision. We have used lateral approach for 20 consecutive tibia fracture patients and report clinical and radiological results after an average follow-up of 31 months. RESULTS: All fractures united, but two malunions were developed after good primary reduction. Seventeen patients achieved excellent or good subjective result while one had moderate and two poor results. Four superficial wound infections were noticed and they were treated conservatively. CONCLUSION: We conclude that lateral approach for the distal tibia is a demanding, but useful surgical method for treatment of the distal tibia fractures especially in cases where no medial comminution of the tibia is present and when the fibula has to be fixed, too. PMID- 17333222 TI - Inhibitory effect of the water-soluble polymer-wrapped derivative of fullerene on UVA-induced melanogenesis via downregulation of tyrosinase expression in human melanocytes and skin tissues. AB - The C60-fullerene derivatives are expected, as novel and potent anti-oxidants, to more effectively protect skin cells against oxidative stress. UVA-induced oxidative stress is considered to promote melanogenesis and serious skin damage. The effect of any fullerene derivatives on UVA-induced melanogenesis is still unknown. Here, we evaluated effects of a water-soluble polyvinylpyrrolidone (PVP) wrapped fullerene derivative (named "Radical Radical Sponge" because of its anti oxidant ability) on melanogenesis, which was promoted by UVA-irradiation to human melanocytes and skin tissues. Radical Sponge markedly scavenged UVA-induced reactive oxygen species (ROS) inside human melanocytes as shown by fluorometry using the redox indicator CDCFH-DA. After treatment with Radical Sponge or other agents, human melanocytes and skin tissues were irradiated by UVA. Then, cellular melanin content, tyrosinase activity and the ultrastructural change of skin melanosomes were examined. Radical Sponge showed to significantly inhibit UVA promoted melanogenesis in normal human epidermis melanocytes (NHEM) and human melanoma HMV-II cells within a non-cytotoxicity dose range. As compared with two whitening agents, arbutin and L-ascorbic acid, Radical Sponge demonstrated the stronger anti-melanogenic potential according to spectrophotometric quantification for extracted melanin. In human skin cultures also, UVA-promoted melanin contents were repressed by Radical Sponge according to Fontana-Masson stain, suggesting its ability to repress UVA-induced tanning. Transmission electron microscopic ultrastructural images also proved that UVA-increased melanosomes in human skin tissue were obviously reduced by Radical Sponge. The UVA-enhanced tyrosinase enzymatic activity in NHEM melanocytes was inhibited by Radical Sponge more markedly than by arbutin and L-ascorbic acid. The UVA enhanced tyrosinase protein expression, together with cell-size fatness and dendrite-formation, was also inhibited more markedly by Radical Sponge according to immunostain and flow cytometry using anti-tyrosinase antibody. Thus the depigmentating action of Radical Sponge might be due to its down-regulating effect on the tyrosinase expression, which is initiated by UVA-caused ROS generation. PMID- 17333223 TI - Remodeling of the human dermis after application of salicylate silanol. AB - Recently, a controlled double-blind study in patients with photo-aged facial skin demonstrated the beneficial role of oral intake of silanol for skin, hair and nails. The aim of our pilot study was to investigate histologic alterations in human skin after injection of silanol. Seven healthy female caucasian volunteers with a moderate degree of photoaged skin received ten sessions of weekly injections of 0.1% salicylate silanol in the left ventral lateral forearm. The histologic features of punch biopsies of the treated area and the nontreated contralateral arm were compared and the collagen and elastic fibers quantified. Texture analysis was performed on digitalized microscopic images by analyzing the Sarkar fractal dimension or amplitudes (inertia values) after Fast Fourier transformation. The treated area revealed a statistically significant increase of the density of both collagen and elastic fibers. Texture analysis showed more compact and homogeneously distributed collagen fibers after silicon injection. Our results suggest that the application of silicon may stimulate the production of collagen and elastic fibers leading to remodeling of the dermal fiber architecture, which may explain the improvement of the skin surface observed in clinical studies. PMID- 17333224 TI - Antifungal susceptibility testing of Trichophyton rubrum by E-test. AB - Trichophyton rubrum isolates were used in susceptibility testing for azoles by E test. Voriconazole was the most and fluconazole was the less-active drug. Our results are in agreement with susceptibility data observed by researchers that used others' methodologies. E-test seems to be a reliable methodology to susceptibility-testing for T. rubrum. PMID- 17333225 TI - HPV induced ovarian squamous cell carcinoma: case report and review of the literature. AB - BACKGROUND: Ovarian squamous cell carcinoma is usually derived from a teratoma, a Brenner tumour or endometriosis. Association with an HPV infection is rare. CASE: A fourth case of ovarian squamous cell cancer associated with HR-HPV is presented. Debulking for stage IIIc ovarian squamous cell cancer was performed and she received adjuvant combination chemotherapy. She developed bone metastases and received radiotherapy. The Progression of these metastases and the newly developed metastases did not respond to an oral tyrosine kinase inhibitor (gefitinib). CONCLUSION: The development of bone metastases in association with an ovarian squamous cell carcinoma is a rare finding, and it did not respond to treatment with a tyrosine kinase. A review of literature is presented. PMID- 17333226 TI - Congenital cytomegalovirus infection in pregnancy: a case report of fetal death in a CMV-infected woman. AB - OBJECTIVES: The human cytomegalovirus (CMV) is universally distributed among human populations as one of the most common cause of congenital infection with an incidence of about 0.15-2.0% in developed countries. However, controversial data concerning intrauterine fetal death caused by CMV infection exist. METHOD: A case report. RESULTS: In this case report we present a stillbirth in the 18th week of pregnancy, caused by a maternal serological and fetal histological congenital CMV infection. CONCLUSION: Every attending physician and obstetrician should be aware of the possibility of a primary or even recurrent congenital CMV infection that could be a reason for sudden unknown congenital fetal death. PMID- 17333227 TI - Oxidative stress as determined by glutathione (GSH) concentrations in venous cord blood in elective cesarean delivery versus uncomplicated vaginal delivery. AB - OBJECTIVE: To determine whether neonates are subject to oxidative stress by the labor process and the mode of delivery by measuring glutathione (GSH) concentrations in umbilical cord venous blood. STUDY DESIGN: Forty-eight women with singleton term pregnancies were prospectively recruited and classified as follows: 26 women had a spontaneous uncomplicated vaginal delivery (VD), and 22 women had an elective cesarean delivery (CD). GSH concentration in umbilical venous blood samples was determined by a spectroscopic method. RESULTS: Umbilical cord venous blood GSH levels were significantly lower in the elective CD group than in the VD group (2.2 and 2.7 mM, respectively, P = 0.0003). There was a significantly negative correlation between cord blood pO(2) and GSH levels; however, the negative correlation was significantly higher in the elective CD group (P < 0.05). CONCLUSION: Neonates delivered by CD were exposed to a higher oxidative stress as determined by GSH levels compared to those who had an uncomplicated VD. PMID- 17333228 TI - Comparison of Nicolaides' risk evaluation for Down's syndrome with a novel software: an analysis of 1,463 cases. AB - OBJECTIVE: The individual risk assessment of fetal Down's syndrome based on measurement of nuchal translucency (NT) according to Nicolaides, optionally complemented by the determination of PAPP-A and free beta HCG has progressively supplanted other search strategies for fetal aneuploidies. It could be shown that this diagnostic strategy equally detects other numeric aneuploidies at a comparable rate. A positive test result is also predictive for the presence of a fetal malformation. In this field, several computer programs are available for clinical use. The objective of our study was to re-evaluate the first consecutive 1463 NT-risk calculations determined by Nicolaides' method and to compare the risk calculation to the JOY software (NT-risk calculation module, JOY Patient Database) introduced in 2002. MATERIAL AND METHODS: At the Department of Obstetrics and Gynecology, Hannover Medical School, 1463 consecutive complete data sets comprising first trimester screening performed between May 2, 2000 and June 26, 2003 and corresponding fetal outcome were analysed using risk assessment based on the Nicolaides method (PIA Fetal Database NT-Module) and compared with the risk evaluation as determined by the JOY software (JOY Patient Database NT module). A risk exceeding 1:300 was considered to indicate the need for further invasive testing. In a first step, only cytogenetically detectable chromosomal aberrations were analysed. Then, a second evaluation including fetal malformations was performed. RESULTS: Among the 1463 cases, 1445 (98.77%) fetuses revealed to be cytogenetically healthy. Both softwares showed identical detection rates at the genetic and somatic level:13 cases of Down-Syndrome (0.89%), 2 cases of trisomy 18 (0.14%), one case of triploidy, one Turner-Syndrome, one Klinefelter-Syndrome (0.07% each) were detected. A positive test result was found in 15 cases ending in a spontaneous abortion, intrauterine death or peripartum death (1.03%) and in 22 cases of fetal malformation (1.50%). At the level of genetic detection the test positive rate dropped from 92 (PIA) to 71 (JOY) ( 22.8%). At the level of combined adverse outcome the test positive rate was reduced from 100 (PIA) to 76 (JOY) (-22.0%), thus yielding in a marked improvement of the characteristic test performance parameters. CONCLUSION: The novel, recently developed JOY software package allowed reliable evaluation of the risk for aneuploidy with increased specificity whereas sensitivity was unchanged. Our data suggest an improvement of the screening for aneuploidy when using this novel software: With an identical detection rate, the number of unnecessary invasive measures may be reduced. PMID- 17333229 TI - Residual hearing in cochlear implant patients. AB - Preservation of residual hearing should be a desirable outcome of implant surgery. Prevention of neural degeneration due to loss of residual hair cells, together with the continuous progress in cochlear implant technology should be able to preserve cochlear integrity as well as possible. The degree of hearing preservation may vary depending on surgical approach, maximum insertion depth and other factors not uniformly considered to date. The aim of this retrospective case controlled study is to evaluate residual hearing after cochlear implant surgery. In particular, we analyzed data obtained with use of two different kinds of electrode arrays, with and without rigid introductor (stylet). We report the results on 37 patients with measurable preoperative hearing thresholds, mean age of 28 years (5-70 years), having the following implants: seven Advanced Bionics, four Med-El, 24 Cochlear, two MXM; 19 of them were performed using the stylet and the other 18 without it. A minimally invasive surgical approach was performed with a short retroauricular incision and a 1.2 mm cochleostomy. A complete electrode array insertion was obtained in all patients. Responses to pure-tone stimuli were measured for each ear in pre-implantation conditions and 3-12 months after surgery. After implantation 14 patients (38%) showed no hearing threshold variation, 29 (78%) maintained an appreciable hearing threshold level in the implanted ear, 8 (22%) had a total loss of residual hearing. Median increases of threshold levels were, in all 37 studied patients, 5, 10, 10 and 5 dB HL, respectively, for 125, 250, 500 and 1 kHz. For the 18 patients having implants without the stylet median increases of threshold levels were 0, 10, 5 and 7 dB HL; in the stylet group, they were 10, 5, 5 and 10 dB HL. On a comparison between the stylet and the non-stylet group, no significant differences in mean hearing threshold worsening were found. Data seem to suggest that cochlear function is less sensitive to mechanical trauma during implant surgery than was thought. Besides, electrode array stiffness seems not to influence preservation of cochlear residual functional integrity. Finally, the authors hypothesize a direct spiral ganglion activation under strong mechanical stimulation. PMID- 17333230 TI - Temporal paragangliomas. AB - Temporal paragangliomas (PGL) are usually limited to the paraganglionar system with a sporadic or familial origin. Familial PGL have recently been shown to be associated with germline alterations in SDH group of genes, and occasionally are associated with a variety of genetic multisystemic disorders (von Hippel-Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1). Temporal bone PGL are normally located in the region of the jugular foramen and on the promontory along the Jacobson nerve. Occasionally, vagal PGL may reach the jugular foramen and behave as jugular PGL. Treatment of temporal PGL must be based on the biological behavior of the tumour, age and medical condition of the patient, location and size of the PGL, and potential for treatment induced morbidity. The main treatment modalities for PGL are surgery and radiation therapy. Patients with large temporal PGL whose resection would result in potentially disabling morbidity are often selected for radiation therapy or wait and scan policy. Small tympanic PGL where resection may be carried out with a low morbidity risk can be removed through an endomeatal tympanotomy. Jugular PGL limited to the infralabyrinthine region involving only the vertical segment of the ICA, can benefit of an extended facial recess approach, which allows a postoperative normal hearing and facial nerve function. For more extensive disease in the middle ear or around the ICA, external auditory canal preservation is not possible and some kind of facial nerve mobilization is required. Preservation of lower cranial nerves is facilitated by intrabulbar dissection, previous extradural ligation of the sigmoid sinus. Management of large intracranial involvement is controversial, although most authors advocate resection of the tumour in a single stage. Surgical control of the tumour can be expected in 70-85% of the patients and is clearly dependent on the tumour stage. Tumour size determines success in hearing and lower cranial nerves preservation. PMID- 17333231 TI - Complications of resection of malignant tumours of the skull base: outcome and solution. AB - The results of surgical resection of malignant tumours located at the skull base have improved significantly over the years. There are however still some complications associated with these procedures. For central skull base lesions, the anterolateral approach exposes the region adequately for an oncological resection to be carried out. The development of palatal fistula in irradiated patient has been a nuisance. With modification of the palatal incision, this problem is now eliminated. For the management of osteoradronecrosis of the skull base, an uncommon late complication, a microvascular free muscle flap is required. For malignant pathologies located at the anterior skull base, a combined craniofacial resection is the treatment of choice. Our experience as well as those reported in the literature showed that when the skull base defect was small, the pericranial and the galeofrontalis flap were adequate for reconstruction. For larger defects, a microvascular free flap would be used. When the internal carotid artery is included in the resection, an extracranial intracranial arterial bypass should be created before the resection of tumour. The most serious complication is the development of cerebral spinal fluid leakage. Conservative treatment is applicable for small leakage while for large leakage; the exact location of the leak must be identified before the defect can be closed successfully. PMID- 17333232 TI - Is current UK management of oesophageal food bolus obstruction evidence based? An e-mail survey and literature review. AB - There is a great deal of variation in individual management of non-sharp oesophageal food bolus obstruction in the United Kingdom. An e-mail survey of consultants and specialist registrars in ENT was carried out to establish current UK practice. A review of the published literature was under-taken to establish whether current practice is evidence based. The majority of practitioners (95%) do not proceed immediately to rigid oesophagoscopy but use antispasmodic drugs (83%), most commonly hyoscine butylbromide (Buscopan) and diazepam, to try to induce spontaneous passage of the obstruction. There is currently no evidence in the published literature to support the use of these drugs. The use of Buscopan seems to have been encouraged by a misquoted reference in a prominent ENT textbook. Better evidence is needed to establish the best form of treatment for this relatively common problem. PMID- 17333233 TI - Radial chromatin positioning is shaped by local gene density, not by gene expression. AB - G- and R-bands of metaphase chromosomes are characterized by profound differences in gene density, CG content, replication timing, and chromatin compaction. The preferential localization of gene-dense, transcriptionally active, and early replicating chromatin in the nuclear interior and of gene-poor, later replicating chromatin at the nuclear envelope has been demonstrated to be evolutionary conserved in various cell types. Yet, the impact of different local chromatin features on the radial nuclear arrangement of chromatin is still not well understood. In particular, it is not known whether radial chromatin positioning is preferentially shaped by local gene density per se or by other related parameters such as replication timing or transcriptional activity. The interdependence of these distinct chromatin features on the linear deoxyribonucleic acid (DNA) sequence precludes a simple dissection of these parameters with respect to their importance for the reorganization of the linear DNA organization into the distinct radial chromatin arrangements observed in the nuclear space. To analyze this problem, we generated probe sets of pooled bacterial artificial chromosome (BAC) clones from HSA 11, 12, 18, and 19 representing R/G-band-assigned chromatin, segments with different gene density and gene loci with different expression levels. Using multicolor 3D flourescent in situ hybridization (FISH) and 3D image analysis, we determined their localization in the nucleus and their positions within or outside the corresponding chromosome territory (CT). For each BAC data on local gene density within 2- and 10-Mb windows, as well as GC (guanine and cytosine) content, replication timing and expression levels were determined. A correlation analysis of these parameters with nuclear positioning revealed regional gene density as the decisive parameter determining the radial positioning of chromatin in the nucleus in contrast to band assignment, replication timing, and transcriptional activity. We demonstrate a polarized distribution of gene-dense vs gene-poor chromatin within CTs with respect to the nuclear border. Whereas we confirm previous reports that a particular gene-dense and transcriptionally highly active region of about 2 Mb on 11p15.5 often loops out from the territory surface, gene dense and highly expressed sequences were not generally found preferentially at the CT surface as previously suggested. PMID- 17333235 TI - Spatial organization of a ubiquitous eukaryotic kinetochore protein network in Drosophila chromosomes. AB - Chromosome segregation during meiosis and mitosis depends on the assembly of functional kinetochores within centromeric regions. Centromeric DNA and kinetochore proteins show surprisingly little sequence conservation despite their fundamental biological role. However, our identification in Drosophila melanogaster of the most diverged orthologs identified so far, which encode components of a kinetochore protein network including the Ndc80 and Mis complexes, further emphasizes the notion of a shared eukaryotic kinetochore design. To determine its spatial organization, we have analyzed by quantitative light microscopy hundreds of native chromosomes from transgenic Drosophila strains coexpressing combinations of red and green fluorescent fusion proteins, fully capable of providing the essential wild-type functions. Thereby, Cenp A/Cid, Cenp-C, Mis12 and the Ndc80 complex were mapped along the inter sister kinetochore axis with a resolution below 10 nm. The C terminus of Cenp-C was found to be near but well separated from the innermost component Cenp-A/Cid. The N terminus of Cenp-C is further out, clustered with Mis12 and the Spc25 end of the rod-like Ndc80 complex, which is known to bind to microtubules at its other more distal Ndc80/Nuf2 end. PMID- 17333234 TI - Cohesin regulation: fashionable ways to wear a ring. AB - Cohesin is a multiprotein complex, conserved from yeast to humans, that mediates sister chromatid cohesion. Its ring-shaped structure first suggested that it may perform its task by embracing the sister chromatids. The interaction of cohesin with chromatin is tightly regulated throughout the cell cycle, and several proteins contribute to cohesin loading and mobilization along DNA, establishment of cohesin-mediated cohesion, and removal of cohesin during mitosis. Recent studies suggest that distinct cohesin populations exist in different chromosomal regions and have particular requirements in their dynamic interaction with chromatin. In this review, I briefly summarize these studies and discuss their implications for current and future models of cohesin behavior. PMID- 17333237 TI - XIST RNA exhibits nuclear retention and exhibits reduced association with the export factor TAP/NXF1. AB - During splicing and polyadenylation, factors that stimulate export from the nucleus are recruited to nascent mRNAs. X-inactive specific transcript (XIST) RNA is unusual among capped, spliced, polyadenylated transcripts in that it accumulates exclusively in the nucleus. It is well established that, at steady state levels, XIST RNA is primarily nuclear. However, it was unknown whether XIST RNA spends its entire lifetime in the nucleus (nuclear retention) or passes briefly through the cytoplasm during maturation, like many other functional RNAs. In this study, we present the first evidence that XIST RNA exhibits nuclear retention. We report that a green fluorescent protein (GFP)-XIST fusion RNA is detected in the nucleus and not the cytoplasm, and GFP is not translated. XIST RNA does not shuttle in a heterokaryon assay or move between chromosomes in the same nucleus when expressed at wild-type levels. These results indicate that XIST RNA's nuclear localization is mediated by nuclear retention rather than export followed by import. We present evidence that the export factor TAP/NXF1 binds poorly to XIST RNA in comparison to exported mRNAs, suggesting that reduced TAP/NFX1 binding may contribute to nuclear retention of XIST RNA. PMID- 17333236 TI - The three-dimensional structure of in vitro reconstituted Xenopus laevis chromosomes by EM tomography. AB - We have studied the in vitro reconstitution of sperm nuclei and small DNA templates to mitotic chromatin in Xenopus laevis egg extracts by three dimensional (3D) electron microscopy (EM) tomography. Using specifically developed software, the reconstituted chromatin was interpreted in terms of nucleosomal patterns and the overall chromatin connectivity. The condensed chromatin formed from small DNA templates was characterized by aligned arrays of packed nucleosomal clusters having a typical 10-nm spacing between nucleosomes within the same cluster and a 30-nm spacing between nucleosomes in different clusters. A similar short-range nucleosomal clustering was also observed in condensed chromosomes; however, the clusters were smaller, and they were organized in 30- to 40-nm large domains. An analysis of the overall chromatin connectivity in condensed chromosomes showed that the 30-40-nm domains are themselves organized into a regularly spaced and interconnected 3D chromatin network that extends uniformly throughout the chromosomal volume, providing little indication of a systematic large-scale organization. Based on their topology and high degree of interconnectedness, it is unlikely that 30-40-nm domains arise from the folding of local stretches of nucleosomal fibers. Instead, they appear to be formed by the close apposition of more distant chromatin segments. By combining 3D immunolabeling and EM tomography, we found topoisomerase II to be randomly distributed within this network, while the stable maintenance of chromosomes head domain of condensin was preferentially associated with the 30-40-nm chromatin domains. These observations suggest that 30-40-nm domains are essential for establishing long-range chromatin associations that are central for chromosome condensation. PMID- 17333238 TI - Intravitreal bevacizumab (Avastin) in combination with verteporfin photodynamic therapy for choroidal neovascularization associated with age-related macular degeneration (IBeVe Study). AB - BACKGROUND: A novel alternative for combined treatment using verteporfin photodynamic therapy (PDT) has emerged as preliminary safety and efficacy data of the intravitreal use of the anti-angiogenic bevacizumab became available. In the current study we investigate the feasibility of intravitreal bevacizumab combined with verteporfin PDT for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: A single-centre, prospective, open-label study of 11 patients with documented CNV progression after PDT treatment who underwent combined PDT and intravitreal injection of 1.5 mg of bevacizumab was undertaken. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 2, 12 and 24. Clinical evidence of complications and changes in logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts and in fluorescein leakage from CNV were evaluated. RESULTS: The mean (+/-SD) age of the 11 patients was 74 (+/-5) years. Seven eyes had been treated with one previous PDT session and four eyes had two previous PDT sessions. The mean baseline logMAR ETDRS BCVA was 1.031 (Snellen equivalent, 20/200(-2)). At follow-up weeks 1, 2, 12 and 24, the mean logMAR ETDRS BCVA (Snellen equivalent) was 0.944 (20/160(-2)), 0.924 (20/160(-1)), 0.882 (20/160(+1)), and 0.933 (20/160(-2)), respectively. The change in BCVA from baseline was significant at each study follow-up interval (P < or = 0.001); at 12 and 24 weeks, the mean change in BCVA from baseline was an improvement of 1.49 and of 0.98 ETDRS line, respectively. Fluorescein leakage from CNV was absent in all eyes at week 12. One additional treatment session was required in seven (63.6%) eyes at week 24 due to recurrent fluorescein leakage from CNV ("minimum" [<50% of the leaking area noted at baseline], n = 4; and "moderate" [>50% of the leaking area noted at baseline], n = 3). No progression of the neovascular lesion was observed at week 24. No safety issues were identified throughout the period of the study. CONCLUSIONS: The overall changes in vision and fluorescein leakage from CNV throughout the study suggest that a possible synergistic effect may arise from the combination of intravitreal bevacizumab with verteporfin PDT for the treatment of neovascular AMD. PMID- 17333239 TI - Ethmoid sinus mucocele presenting as transient monoocular altitudinal hemianopia. AB - INTRODUCTION: We report a case of a transient monocular altitudinal hemianopia associated with ethmoid mucocele. METHODS: A 34-year-old man presented with an episode of superior altitudinal hemianopia in the left eye that had lasted for about 10 minutes and then spontaneously improved three weeks ago. RESULTS: Humphrey visual fields showed normal visual field in both eyes. Exophthalmometry showed 18 mm in the right eye and 18.5 mm in the left. Magnetic resonance imaging of the orbit revealed a 2.5 cm-sized left posterior ethmoid mucocele. CONCLUSIONS: To the best of our knowledge, this may be the first report of mucocele associated with transient altitudinal hemianopia. The described findings may facilitate the diagnosis of mucocele in patients who present with a monocular altitudinal hemianopia. PMID- 17333240 TI - Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR delta) in mouse tissues using tissue microarray. AB - Peroxisome proliferator-activated receptor-delta (PPAR-delta) is known as a transcription factor involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in several tissues, such as skeletal muscle, liver and adipose tissues. In this study, to elucidate systemic physiological functions of PPAR-delta, we examined the tissue distribution and localization of PPAR-delta in adult mouse tissues using tissue microarray (TMA)-based immunohistochemistry. PPAR-delta positive signals were observed on variety of tissues/cells in multiple systems including cardiovascular, urinary, respiratory, digestive, endocrine, nervous, hematopoietic, immune, musculoskeletal, sensory and reproductive organ systems. In these organs, PPAR-delta immunoreactivity was generally localized on the nucleus, although cytoplasmic localization was observed on several cell types including neurons in the nervous system and cells of the islet of Langerhans. These expression profiling data implicate various physiological roles of PPAR delta in multiple organ systems. TMA-based immunohistochemistry enables to profile comprehensive protein localization and distribution in a high-throughput manner. PMID- 17333241 TI - Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries. AB - OBJECTIVES: Workers in the rubber industry are exposed to a complex mixture of hazardous substances and have increased risk of developing several diseases. However, there is no up to date survey examining the exposure in the Swedish rubber industry. One of the toxic compounds in the industry is carbon disulfide (CS(2)), which is biotransformed to 2-thiothiazolidine-4-carboxylic acid (TTCA). TTCA is used as a biomarker of CS(2) exposure, but there seem to exist inter- and intraindividual variability; which could partly be due to genetic variation. The aim of the study was to determine TTCA levels and the modifying effects of glutathione-related genes in a group of Swedish rubber workers. METHODS: Urine was collected from both exposed workers and controls during the last 4 h of the work shift. The level of TTCA in urine was analyzed by liquid chromatograpy tandem mass spectrometry. Genotyping of the single nucleotide polymorphisms GCLC 129, GCLM-588, GSTA1-52, GSTP1-105 and GSTP1-114 and deletions of GSTM1 and GSTT1 were performed with real-time PCR or ordinary PCR and subsequent agarose electrophoresis. RESULTS: The highest levels of TTCA were found among workers curing with salt bath, hot air, microwaves or fluid-bed, and lower levels were found among workers curing with injection and compression molding. Furthermore, with respect to GSTM1 and GSTT1 there were statistically significant differences in TTCA-levels between genotypes among exposed workers but not among controls. The other five polymorphisms had no impact on the TTCA levels. CONCLUSIONS: The present study demonstrates relatively high levels of TTCA in urine from Swedish rubber workers. Polymorphisms in GSTM1 and GSTT1 modify the levels. PMID- 17333242 TI - Increased oxidative stress indices in the blood of child swimmers. AB - The blood redox status of child athletes is compared with that of age-matched untrained individuals. In the present study, 17 swimmers (10.1 +/- 1.6 years) and 12 non-athletes (9.9 +/- 1.1 years) participated. Reduced glutathione (GSH) was lower by 37% in swimmers compared to non-athletes (P < 0.01), oxidized glutathione (GSSG) was not different and their ratio (GSH/GSSG) was lower by 43% in swimmers compared to non-athletes (P < 0.01). Thiobarbituric acid-reactive substances concentration was higher by 25% in swimmers compared to controls. Catalase exhibited a strong trend toward lower levels in swimmers (P = 0.08). Finally, total antioxidant capacity was found lower by 28% in swimmers compared to controls (P < 0.05). In conclusion, we report that children participating in swimming training exhibit increased oxidative stress and less antioxidant capacity compared to untrained counterparts and suggest that children may be more susceptible to oxidative stress induced by chronic exercise. PMID- 17333243 TI - Postural control in elderly subjects participating in balance training. AB - The changes in postural control in elderly people after an 8-week training course were characterized. Static postural stability was measured during standing on a single force platform first with the eyes open and then with the eyes closed. Body sway was analysed on a force plate in groups of elderly and of young subjects. Half of the elderly subjects then took part in the training course. The posturographic measurements were repeated after the course. The sway in anteroposterior (AP) and mediolateral (ML) directions was subjected to spectral analysis. The frequency spectrum of the platform oscillations was calculated by fast Fourier transformation in the intervals 0.1-0.3, 0.3-1 and 1-3 Hz. It was found that the sway path was longer and the frequency power was higher in the elderly group. The training caused a significant improvement in functional performance, but a significantly longer sway path was observed after the training in the ML direction. The frequency analysis revealed a significantly higher power after 8 weeks without visual control in the ML direction in the training group in the low and the middle frequency bands. The results suggest that the participants' balance confidence and the control of ML balance improved in response to the training. The higher ML frequency power exhibited after the training may be indicative of a better balance performance. Thus, the increase in the sway path in this age group did not mean a further impairment of the postural control. PMID- 17333244 TI - Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use. AB - Using contemporary stable-isotope methodology and fluorescence microscopy, we assessed the impact of carbohydrate supplementation on whole-body and fiber-type specific intramyocellular triacylglycerol (IMTG) and glycogen use during prolonged endurance exercise. Ten endurance-trained male subjects were studied twice during 3 h of cycling at 63 +/- 4% of maximal O(2) uptake with either glucose ingestion (CHO trial; 0.7 g CHO kg(-1) h(-1)) or without (CON placebo trial; water only). Continuous infusions with [U-(13)C] palmitate and [6,6 (2)H(2)] glucose were applied to quantify plasma free fatty acids (FFA) and glucose oxidation rates and to estimate intramyocellular lipid and glycogen use. Before and after exercise, muscle biopsy samples were taken to quantify fiber type-specific IMTG and glycogen content. Plasma glucose rate of appearance (R (a)) and carbohydrate oxidation rates were substantially greater in the CHO vs CON trial. Carbohydrate supplementation resulted in a lower muscle glycogen use during the first hour of exercise in the CHO vs CON trial, resulting in a 38 +/- 19 and 57 +/- 22% decreased utilization in type I and II muscle-fiber glycogen content, respectively. In the CHO trial, both plasma FFA R (a) and subsequent plasma FFA concentrations were lower, resulting in a 34 +/- 12% reduction in plasma FFA oxidation rates during exercise (P < 0.05). Carbohydrate intake did not augment IMTG utilization, as fluorescence microscopy revealed a 76 +/- 21 and 78 +/- 22% reduction in type I muscle-fiber lipid content in the CHO and CON trial, respectively. We conclude that carbohydrate supplementation during prolonged cycling exercise does not modulate IMTG use but spares muscle glycogen use during the initial stages of exercise in endurance-trained men. PMID- 17333246 TI - Biological activity of FGF-23 fragments. AB - The phosphaturic activity of intact, full-length, fibroblast growth factor-23 (FGF-23) is well documented. FGF-23 circulates as the intact protein and as fragments generated as the result of proteolysis of the full-length protein. To assess whether short fragments of FGF-23 are phosphaturic, we compared the effect of acute, equimolar infusions of full-length FGF-23 and various FGF-23 fragments carboxyl-terminal to amino acid 176. In rats, intravenous infusions of full length FGF-23 and FGF-23 176-251 significantly and equivalently increased fractional phosphate excretion (FE Pi) from 14 +/- 3 to 32 +/- 5% and 15 +/- 2 to 33 +/- 2% (p < 0.001), respectively. Chronic administration of FGF-23 176-251 reduced serum Pi and serum concentrations of 1alpha,25-dihydroxyvitamin D. Shorter forms of FGF-23 (FGF-23 180-251 and FGF-23 184-251) retained phosphaturic activity. Further shortening of the FGF-23 carboxyl-terminal domain, however, abolished phosphaturic activity, as infusion of FGF-23 206-251 did not increase urinary phosphate excretion. Infusion of a short fragment of the FGF-23 molecule, FGF-23 180-205, significantly increased FE Pi in rats and reduced serum Pi in hyperphosphatemic Fgf-23 ( -/- ) knockout mice. The activity of FGF-23 180-251 was confirmed in opossum kidney cells in which the peptide reduced Na(+) dependent Pi uptake and enhanced internalization of the Na(+)-Pi IIa co transporter. We conclude that carboxyl terminal fragments of FGF-23 are phosphaturic and that a short, 26-amino acid fragment of FGF-23 retains significant phosphaturic activity. PMID- 17333245 TI - Adaptive response to increased bile acids: induction of MDR1 gene expression and P-glycoprotein activity in renal epithelial cells. AB - Cholestatic liver disease and increased serum bile acid concentrations are known to trigger various adaptive responses including the induction of hepatic, intestinal and renal bile acid transport proteins, but renal P-glycoprotein (Pgp, multidrug resistance protein 1, MDR1) remained uninvestigated in this context. We show that treatment of Madin Darby canine kidney (MDCK) cells with pathophysiologically relevant concentrations of chenodeoxycholic acid (CDCA; 100 microM) for 12 h induces MDR1 transcript levels in vitro more than twofold. CDCA and deoxycholic acid pre-treatment for 24-96 h (100 microM) also increased Pgp activity measured as rhodamine efflux, while cholic acid and taurocholic acid were not effective in concentrations up to 600 microM. CDCA pre-treatment (100 microM, 72 h) also resulted in a doubling of rhodamine123 secretion across an epithelium-like monolayer grown on Transwell filters and decreased the sensitivity towards the kidney toxic drugs cyclosporine A and paclitaxel. These findings predict physiologically as well as pharmacologically relevant consequences of liver disease for Pgp substrate transport and toxicity in the kidneys. PMID- 17333247 TI - Gating of the HypoPP-1 mutations: II. Effects of a calcium-channel agonist BayK 8644. AB - L-type calcium-channel mutations causing hypokalemic periodic paralysis type 1 (HypoPP-1) have pronounced "loss-of-function" features and stabilize the less selective second open state O(2), as we demonstrated in the companion paper. Here, we compared the effects of the L-type calcium-channel activator (+/-)BayK 8644 (BayK) on the heterologously expressed wild-type (WT) calcium channel, rabbit Cav1.2 HypoPP-1 analogs, and two double mutants (R650H/R1362H, R650H/R1362G). Our goal was to elucidate (1) whether the "loss-of-function" in HypoPP-1 can be compensated by BayK application, (2) how the less-selective open state is affected by BayK in WT and HypoPP-1 mutants, as well as (3) to gain an insight into BayK mechanism of action. Ionic currents were examined by whole-cell patch-clamp and analyzed by the global-fitting procedure. Our results imply that (1) BayK promotes channel activation, but equalized the differences among the WT and mutants, thus attenuating HypoPP-related effects on activation and deactivation; (2) BayK binds to the first open state O(1), and then serves as a catalyst for O(2) formation; (3) binding of BayK is impaired in the HypoPP mutants, thus affecting the formation of the less-selective second open state; (4) BayK affects cooperativity between the single HypoPP-1 mutations at all stages of the channel gating; and (5) BayK favoring of O(2) lowers calcium channel selectivity. PMID- 17333248 TI - Modulation of the transient outward K+ current by inhibition of endothelin-A receptors in normal and hypertrophied rat hearts. AB - Inhibition of endothelin-A (ET(A)) receptors has been shown to reduce ventricular electrical abnormalities associated with cardiac failure. In this study, we investigate the effect of ET(A)-receptor inhibition on the development of regional alterations of the transient outward K(+) current (I (to)) in the setting of pressure-induced left ventricular (LV) hypertrophy. Cardiac hypertrophy was induced in female Sprague-Dawley rats by stenosis of the ascending aorta (AS) for 7 days. Treatment with the selective ET(A)-receptor antagonist darusentan (LU135252, 35 mg [kg body weight](-1) day(-1)) was started 1 day before the surgery. AS induced a 46% increase in the relative LV weight (p < 0.001) and caused a significant reduction in I (to) (at +40 mV) in epicardial myocytes (19.5 +/- 1.2 pA pF(-1), n = 32 vs 23.2 +/- 1.2 pA pF(-1), n = 35, p < 0.05). Darusentan further reduced I (to) in AS (15.4 +/- 1.3 pA pF(-1), n = 37, p < 0.05) and sham-operated animals (19.8 +/- 1.6 pA pF(-1), n = 48, ns.). The effects of AS and darusentan on I (to) were significant and independent as tested by two-way analysis of variance. I (to) was not affected in endocardial myocytes. These results indicate that endothelin-1 may exert a tonic effect on the magnitude of I (to) in the epicardial region of the left ventricle but that ET(A) receptor activation is not necessary for the development of electrical alterations associated with pressure-induced hypertrophy. PMID- 17333249 TI - Gating of the HypoPP-1 mutations: I. Mutant-specific effects and cooperativity. AB - Hypokalemic periodic paralysis type 1 (HypoPP-1) is a hereditary muscular disorder caused by point mutations in the gene encoding the voltage-gated Ca(2+) channel alpha subunit (Ca(v)1.1). Despite extensive research, the results on HypoPP-1 mutations are minor and controversial, as it is difficult to analyse Ca(2+) channel activation macroscopically due to an existence of two open states. In this study, we heterologously expressed the wild-type and HypoPP-1 mutations introduced into the rabbit cardiac Ca(2+) channel (R650H, R1362H, R1362G) in HEK 293 cells. To examine the cooperative effects of the mutations on channel gating, we expressed two double mutants (R650H/R1362H, R650H/R1362G). We performed whole cell patch-clamp and, to obtain more information, applied a global fitting procedure whereby several current traces elicited by different potentials were simultaneously fit to the kinetic model containing four closed, two open and two inactivated states. We found that all HypoPP-1 mutations have "loss-of-function" features: D4/S4 mutations shift the equilibrium to the closed states, which results in reduced open probability, shorter openings and, therefore, in smaller currents, and the D2/S4 mutant slows the activation. In addition, HypoPP-1 histidine mutants favored the second open state O(2) with a possibly lower channel selectivity. Cooperativity between the D2/S4 and D4/S4 HypoPP-1 mutations manifested in dominant effects of the D4/S4 mutations on kinetics of the double mutants, suggesting different roles of D2/S4 and D4/S4 voltage sensors in the gating of voltage-gated calcium channels. PMID- 17333250 TI - Two NAC domain transcription factors, SND1 and NST1, function redundantly in regulation of secondary wall synthesis in fibers of Arabidopsis. AB - Secondary walls are the major component of wood, and studies of the mechanisms regulating secondary wall synthesis is important for understanding the process of wood formation. We have previously shown that the NAC domain transcription factor SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1) is a key regulator of secondary wall synthesis in fibers of Arabidopsis thaliana stems and dominant repression of SND1 leads to a reduction in secondary wall thickening in fibers. However, T-DNA knockout of the SND1 gene did not cause an alteration in secondary wall thickness, suggesting that other SND1 homologs may compensate for the loss of SND1 expression. Here, we studied the effects of simultaneous inhibition of SND1 and its homolog, NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1), on secondary wall synthesis in fibers. We show that simultaneous RNA interference (RNAi) inhibition of the expression of both SND1 and NST1 genes results in loss of secondary wall formation in fibers of stems. The fiber cells in the stems of SND1/NST1-RNAi plants lack all three major secondary wall components, including cellulose, xylan, and lignin, which is accompanied by a severe reduction in the expression of genes involved in their biosynthesis. In addition, inhibition of SND1 and NST1 leads to down-regulation of several fiber-associated transcription factor genes. Double T-DNA knockout mutations of SND1 and NST1 genes cause the same effects, as does simultaneous RNAi inhibition of SND1 and NST1. Our results provide first line evidence demonstrating that SND1 and NST1 function redundantly in the regulation of secondary wall synthesis in fibers. PMID- 17333251 TI - Identification of conserved tyrosine residues important for gibberellin sensitivity of Arabidopsis RGL2 protein. AB - DELLA proteins are regulators in the signaling pathway of gibberellin (GA), a plant growth regulator of diverse functions. GA typically induces the degradation of DELLA proteins to overcome their repressive roles in growth and development. We have previously evaluated the likely roles of Ser-Thr phosphorylation of DELLA proteins in GA signaling (Hussain et al., Plant J 44:88-99, 2005). Here we report that four DELLA proteins of Arabidopsis, namely GAI, RGL1, RGL2 and RGL3, expressed in tobacco BY2 cells, are degradable by GA. Both, proteasome inhibitor and protein tyrosine (Tyr) kinase inhibitors, strongly inhibit GA-induced DELLA degradation whereas phospho-Tyr phosphatase inhibitors have no effect, suggesting that Tyr phosphorylation is critical in GA-induced DELLA degradation. Mutation of eight conserved Tyr residues of RGL2 into alanine shows four mutant proteins (Y52A, Y89A, Y223A and Y435A) are resistant to GA-induced degradation. Substitution of these four critical Tyr residues into negatively charged glutamate (Y --> E) also resulted in stabilization of these mutants against GA treatment. However, further mutation of these four Tyrs into conservative phenylalanine (Y --> F) rendered the mutant proteins sensitive to GA like the wild-type RGL2. Since Y --> E mutations sometimes mimic phosphor-Tyr whereas Y - > F mutations render the protein unphosphorylatable at these Tyr sites, we conclude that these four conserved Tyrs, despite being critical for GA sensitivity, are unlikely to be sites of Tyr phosphorylation but instead play important roles in maintaining the structure integrity of RGL2 for GA sensitivity. PMID- 17333252 TI - Nitrite-driven anaerobic ATP synthesis in barley and rice root mitochondria. AB - Mitochondria isolated from the roots of barley (Hordeum vulgare L.) and rice (Oryza sativa L.) seedlings were capable of oxidizing external NADH and NADPH anaerobically in the presence of nitrite. The reaction was linked to ATP synthesis and nitric oxide (NO) was a measurable product. The rates of NADH and NADPH oxidation were in the range of 12-16 nmol min(-1) mg(-1) protein for both species. The anaerobic ATP synthesis rate was 7-9 nmol min(-1) mg(-1) protein for barley and 15-17 nmol min(-1) mg(-1) protein for rice. The rates are of the same order of magnitude as glycolytic ATP production during anoxia and about 3-5% of the aerobic mitochondrial ATP synthesis rate. NADH/NADPH oxidation and ATP synthesis were sensitive to the mitochondrial inhibitors myxothiazol, oligomycin, diphenyleneiodonium and insensitive to rotenone and antimycin A. The uncoupler FCCP completely eliminated ATP production. Succinate was also capable of driving ATP synthesis. We conclude that plant mitochondria, under anaerobic conditions, have a capacity to use nitrite as an electron acceptor to oxidize cytosolic NADH/NADPH and generate ATP. PMID- 17333253 TI - A glucocorticoid-inducible gene expression system can cause growth defects in tobacco. AB - We find that an expression system widely used to chemically induce transgenes of interest in tobacco (Nicotiana tabacum Petit Havana SR1) can cause severe growth defects in this species. This gene expression system has been shown to cause non specific effects (including growth retardation) in other plant species, but has until now been largely accepted to be a relatively problem-free system for use in tobacco. The expression system is based on the ability of the glucocorticoid dexamethasone (DEX) to activate a non-plant chimeric transcription factor (GVG), which then activates expression of a transgene of interest. The aberrant growth phenotype only manifests itself after DEX application and only occurs in plants in which the constitutive levels of GVG expression are higher than average. We found that approximately 30% of all transgenic plants produced showed some level of growth retardation under our standard growth conditions. However, by modulating irradiance levels following DEX application, we also showed that the manifestation and severity of the aberrant phenotype is highly dependent upon growth conditions, highlighting that such conditions are a critical parameter to consider during all stages of using this gene expression system. We also identified an increase in ACC oxidase gene expression as an early, sensitive and robust molecular marker for the aberrant phenotype. This molecular marker should be valuable to investigators wishing to readily identify transgenic plants in which GVG expression levels are beyond a threshold that begins to produce non specific effects of the gene expression system under a defined set of growth conditions. PMID- 17333254 TI - Complex formation regulates the glycosylation of the reversibly glycosylated polypeptide. AB - Reversible glycosylated polypeptides (RGPs) are highly conserved plant-specific proteins, which can perform self-glycosylation. These proteins have been shown essential in plants yet its precise function remains unknown. In order to understand the function of this self-glycosylating polypeptide, it is important to establish what factors are involved in the regulation of the RGP activity. Here we show that incubation at high ionic strength produced a high self glycosylation level and a high glycosylation reversibility of RGP from Solanum tuberosum L. In contrast, incubation at low ionic strength led to a low level of glycosylation and a low glycosylation reversibility of RGP. The incubation at low ionic strength favored the formation of high molecular weight RGP-containing forms, whereas incubation at high ionic strength produced active RGP with a molecular weight similar to the one expected for the monomer. Our data also showed that glycosylation of RGP, in its monomeric form, was highly reversible, whereas, a low reversibility of the protein glycosylation was observed when RGP was part of high molecular weight structures. In addition, glycosylation of RGP increased the occurrence of non-monomeric RGP-containing forms, suggesting that glycosylation may favor multimer formation. Finally, our results indicated that RGP from Arabidopsis thaliana and Pisum sativum are associated to golgi membranes, as part of protein complexes. A model for the regulation of the RGP activity and its binding to golgi membranes based on the glycosylation of the protein is proposed where the sugars linked to oligomeric form of RGP in the golgi may be transferred to acceptors involved in polysaccharide biosynthesis. PMID- 17333255 TI - Studies of xylan interactions and cross-linking to synthetic lignins formed by bulk and end-wise polymerization: a model study of lignin carbohydrate complex formation. AB - The mechanism of lignin carbohydrate complex formation by addition of polysaccharides on quinone methide (QM) generated during lignin polymerisation was investigated using a model approach. Dehydrogenation polymers (DHPs, lignin model compounds) were synthesized from coniferyl alcohol in the presence of a glucuronoarabinoxylan (GAX) extracted from oat spelts, by Zutropfverfahren (ZT) and Zulaufverfahren (ZL) methods. The methods ZT and ZL differed in their distribution of QM over the reaction period but generated roughly the same QM amount. Steric exclusion chromatography of the ZT and ZL reaction products showed that only the ZT reaction produced high molar mass compounds. Covalent linkages in the ZT reaction involving ether bonds between GAX moiety and alpha carbon of the lignin monomer were confirmed by (13)C NMR and xylanase-based fractionation. The underlying phenomena were further investigated by examining the interactions between GAX and DHP in sorption experiments. GAX and DHPs were shown to interact to form hydrophobic aggregates. In the ZT process, slow addition permitted polymer reorganisation which led to dehydration around the lignin-like growing chains thereby limiting the addition of water on the quinone methide formed during polymerisation and thus favoured lignin-carbohydrate complex (LCC) formation. PMID- 17333256 TI - Mislocalization of a target toward subjective contours: attentional modulation of location signals. AB - This study examined whether a briefly presented target was mislocalized toward a subjective contour. Observers manually reproduced the position of a briefly presented peripheral target circle above a central fixation cross. A luminance contour, a subjective contour, or a no-contour stimulus was presented in either the left of right visual field, and a no-contour control was presented in the opposite visual field. After these stimuli vanished, a target circle was then presented. Consequently, the degree of mislocalization toward the subjective and luminance contours was the same; this indicated that image integration at a coarse spatial scale cannot explain mislocalization. Experiment 2 revealed that the mislocalization in Experiment 1 was not a result of eye movements. Experiment 3 found that the spatial attention allocated at the location of the luminance and subjective contours was more than that allocated at the no-contour stimulus. An attentional shift toward the task-irrelevant stimulus resulted in a mislocalization of the target. PMID- 17333257 TI - Identification and analysis of cabut orthologs in invertebrates and vertebrates. AB - Cabut (cbt) is a Drosophila melanogaster gene involved in epidermal dorsal closure (DC). Its expression is dependent on the Jun N-terminal kinase (JNK) cascade, and it functions downstream of Jun regulating dpp expression in the leading edge cells. The Cbt protein contains three C(2)H(2)-type zinc fingers and a serine-rich domain, suggesting that it functions as a transcription factor. We have identified single cbt orthologs in other Drosophila species, as well as in other insects and invertebrate organisms like ascidians and echinoderms, but not in nematodes. Gene structure and protein sequence are highly conserved among Drosophilidae, but are more diverged in the other species of invertebrates analyzed. According to this, we demonstrate that cbt expression is detected in the embryonic lateral epidermis in several Drosophila species, as it occurs in D. melanogaster, thus suggesting that the cbt orthologs may have a conserved role in these species during DC. We have also analyzed the genomes of several vertebrate species, finding that the cbt orthologous genes in these organisms encode proteins that belong to the TIEG family of Sp1-like/Kruppel-like transcription factors. Phylogenetic analysis of the invertebrate and vertebrate proteins identified indicates that they mainly follow the expected phylogeny of the species, and that the cbt gene was duplicated during vertebrate evolution. Because we were not able to identify cbt orthologous genes neither in yeast nor in plants, our results suggest that this gene has been probably conserved throughout metazoans and that it may play a fundamental role in animal biology. PMID- 17333258 TI - Differential expression of two vasa/PL10-related genes during gametogenesis in the special model system Rana. AB - Germline cell fate decisions are primarily controlled at the post-transcriptional level with DEAD-box RNA helicases playing a crucial role in germline development. In this study, we report the identification of two DEAD-box vasa/PL10 orthologues (RlVlg and RlPL10) in a species complex of the genus Rana, characterized by hybridogenetic reproduction, an enigmatic process that involves the exclusion of an individual genome, and endoreduplication events. Both genes were expressed during the early stages of gametogenesis of R. ridibunda, R. lessonae, and their natural hybrid R. esculenta. RlVlg expression was germline specific. On the other hand, RlPL10 was also expressed in somatic tissues, although only at low levels. The two genes were expressed in different phases of mitotic and meiotic spermatogenetic divisions as demonstrated by immunostaining with an anti-H3 phosphohistone antibody. The data indicate that RlVlg and RlPL10 may represent useful markers for dissecting the molecular aspects of genome exclusion and endoreduplication of the hybridogenetic gametogenesis. PMID- 17333259 TI - Apvasa marks germ-cell migration in the parthenogenetic pea aphid Acyrthosiphon pisum (Hemiptera: Aphidoidea). AB - In the parthenogenetic and viviparous pea aphid Acyrthosiphon pisum, germline specification depends on the germ plasm localized to the posterior region of the egg chamber before the formation of the blastoderm. During blastulation, germline segregation occurs at the egg posterior, and in early gastrulation germ cells are pushed inward by the invaginating germ band. Previous studies suggest that germ cells remain dorsal in the embryo in subsequent developmental stages. In fact, though, it is not known whether germ cells remain in place or migrate dynamically during katatrepsis and germ-band retraction. We cloned Apvasa, a pea aphid homologue of Drosophila vasa, and used it as a germline marker to monitor the migration of germ cells. Apvasa messenger RNA (mRNA) was first restricted to morphologically identifiable germ cells after blastoderm formation but that expression soon faded. Apvasa transcripts were again identified in germ cells from the stage when the endosymbiotic bacteria invaded the embryo, and after that, Apvasa mRNA was present in germ cells throughout all developmental stages. At the beginning of katatrepsis, germ cells were detected at the anteriormost region of the egg chamber as they were migrating into the body cavity. During the early period of germ-band retraction, germ cells were separated into several groups surrounded by a layer of somatic cells devoid of Apvasa staining, suggesting that the coalescence between migrating germ cells and the somatic gonadal mesoderm occurs between late katatrepsis and early germ-band retraction. PMID- 17333260 TI - Duplicated Abd-B class genes in medaka hoxAa and hoxAb clusters exhibit differential expression patterns in pectoral fin buds. AB - Hox genes form clusters. Invertebrates and Amphioxus have only one hox cluster, but in vertebrates, they are multiple, i.e., four in the basal teleost fish Polyodon and tetrapods (HoxA, B, C, D), but seven or eight in common teleosts. We earlier completely sequenced the entire hox gene loci in medaka fish, showing a total of 46 hox genes to be encoded in seven clusters (hoxAa, Ab, Ba, Bb, Ca, Da, Db). Among them, hoxAa, hoxAb and hoxDa clusters are presumed to be important for fin-to-limb evolution because of their key role in forelimb and pectoral fin development. In the present study, we compared genome organization and nucleotide sequences of the hoxAa and hoxAb clusters to these of tetrapod HoxA clusters, and found greater similarity in hoxAa case. We then analyzed expression of Abd-B family genes in the clusters. In the trunk, those from the hoxAa cluster, i.e., hoxA9a, hoxA10a, hoxA11a and hoxA13a, were expressed in a manner keeping the colinearity rule of the hox expression as those of tetrapods, while those from the hoxAb cluster, i.e., hoxA9b, hoxA10b, hoxA11b and hoxA13b, were not. In the pectoral fins, the hoxAa cluster was expressed in split domains and did not obey the rule. By contrast, those from the hoxAb and hoxDa clusters were expressed in a manner keeping the rule, i.e., an ancestral pattern similar to those of tetrapods. It is plausible that this differential expression of the two clusters is caused by changes occurred in global control regions after cluster duplications. PMID- 17333261 TI - Multicentric invasive carcinomas derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreas: report of a case. PMID- 17333262 TI - Prevalence of Toxocara-induced liver granulomas, detected by immunohistochemistry, in a series of autopsies at a Children's Reference Hospital in Vitoria, ES, Brazil. AB - The aim of this investigation was to study the frequency of visceral larva migrans (VLM) granulomas in autopsies at a Children's Reference Hospital in Vitoria, ES Brazil, where anti-Toxocara antibodies are frequently detected in the serum of children admitted at the hospital. Two liver fragments from 310 autopsies of children aged between 1 and 15 years were paraffin embedded, and sections were stained with hematoxylin and eosin and submitted to detection of Toxocara antigens using a rabbit anti-Toxocara serum. Among the 24 cases with granulomatous lesions, ten had eosinophil-rich granulomas positively stained with the anti-Toxocara serum. Some were typical epithelioid granulomas, with a positive reaction in multinucleated giant cells, epithelioid cells, or necrotic debris. The results showed that VLM granulomas are the most frequent granulomatous hepatitis in children in our county. This agrees with the high prevalence of anti-Toxocara antibodies in the serum of children admitted to the Children's Reference Hospital. The 3.2% frequency of liver VLM granulomas in autopsies is less than the 30-39% frequency of positive serology in these children, probably reflecting the low larval burden in infected children. PMID- 17333263 TI - Expression changes of the MAD mitotic checkpoint gene family in renal cell carcinomas characterized by numerical chromosome changes. AB - Papillary and chromophobe renal cell carcinomas are characterized by multiple trisomies and monosomies, respectively, but the molecular mechanisms behind the acquisition of these numerical chromosome changes are unknown. To evaluate the role of mitotic checkpoint defects for the karyotypic patterns characteristic of these two renal cell cancer subtypes, we analyzed the messenger RNA expression levels of the major mitotic checkpoint genes of the budding uninhibited by benzimidazole family (BUB1, BUBR1, BUB3) and of the mitotic arrest deficiency family (MAD1, MAD2L1, MAD2L2) by real-time quantitative polymerase chain reaction in 30 renal cell cancer samples (11 chromophobe and 19 papillary) and 36 normal kidney tissue samples. MAD1, MAD2L1, and MAD2L2 showed significant expression differences in tumor tissue compared to controls. Chromophobe tumors presented underexpression of MAD1, and MAD2L2, whereas papillary tumors showed overexpression of MAD2L1. The expression level of the BUB gene family did not differ significantly from that of normal kidney. We conclude that expression changes in mitotic arrest deficiency genes (MAD1, MAD2L1, and MAD2L2) play a role in renal carcinogenesis characterized by multiple numerical chromosome abnormalities. PMID- 17333264 TI - Molecular-cytogenetic characterisation of sex cord-stromal tumours: CGH analysis in sertoli cell tumours of the testis. AB - Sertoli cell tumours (SCT) are rare and poorly explored neoplasias, and the genetic features of these uncommon tumours are largely unknown. Data about chromosomal aberrations in human SCT of the testis are very rare. We present in this paper the first molecular-cytogenetic study of SCT of the testis. DNA was isolated from paraffin-embedded tumour material from 11 patients with unilateral SCT. We used comparative genomic hybridisation to investigate changes in DNA copy number. The detected DNA imbalances showed variation from case to case, indicating a high genetic heterogeneity. Chromosomal aberrations were detected in 9 of the 11 tumours evaluated, with 13 losses versus 14 gains. The most frequent aberrations detected were gain of chromosome X (5 of 11 cases) followed by losses of entire or part of chromosomes 2 and 19 in three cases. This study suggests a high variability in histomorphological and genetic patterns. Only gain of the entire chromosome X seems to be a frequent aberration in these tumours. Further studies of these tumour types are necessary to clarify the significance of chromosomal alterations in carcinogenesis of SCT. PMID- 17333265 TI - Aurora-A/STK-15 is a predictive factor for recurrent behaviour in non-invasive bladder carcinoma: a study of 128 cases of non-invasive neoplasms. AB - Aurora-A, a member of serine/threonine kinase, is implied in mitosis and centrosome maturation. Increasing levels of Aurora-A have been shown to be present in several malignancies and especially in bladder cancer. No immunohistochemical marker has shown to be able to predict the clinical outcome of patients with superficial bladder cancer, except MIB-1, as a predictive marker of relapse and progression. The aim was to investigate the expression of Aurora-A and MIB-1 in tissue micro arrays of superficial bladder cancer representative of pTa papillary urothelial neoplasm with different degrees of aggressiveness (low malignant potential [PUNLMP], non-invasive papillary urothelial carcinoma low grade [NILGC], non-invasive papillary urothelial carcinoma high grade [NIHGC] and carcinoma in situ). We analysed predictive values of both markers, their specificity and sensitivity in tumor recurrence. Aurora-A was a sensitive marker to predict tumor recurrence especially for pTa (PUNLMP, NILGC; PUNLMP p<0.001, NILGC p<0.001) with statistical significant correlation between immunohistochemical staining and clinical outcome. MIB-1 expression displayed statistical difference p=0.002 in the PUNLMP group and p=0.03 in the NILGC group. Aurora-A is a more sensitive marker than MIB-1 to predict relapse in pTa bladder neoplasias. The combination of both markers seems to have a very powerful predictive value of recurrence (p<0.001). PMID- 17333266 TI - Liver histology in patients with sporadic acute hepatitis E: a study of 11 patients from South-West France. AB - Hepatitis E virus is a ribonucleic acid (RNA) enterically transmitted virus that causes both epidemics and sporadic cases of acute hepatitis E in many countries of Asia and Africa. Domestically acquired (non-travel-associated) hepatitis E has been reported recently in many industrialized countries including the USA, Europe, and Japan. There is little information available on liver histology in these patients. We report a series of 11 patients with sporadic acute hepatitis E and needle liver histology in South-West France. Hepatitis E was diagnosed based on elevated transaminases (>10 upper limit normal) and the presence of specific serum antibodies (immunoglobulin-G class, present in all 11 patients) and/or viral RNA detection in serum and/or stools. Acute hepatitis lesions were observed in all cases with marked necro-inflammatory activity in nine patients. Confluent necrosis was present in five cases. Anisocaryosis and Kupffer's cell aggregates with siderosis were observed in most of the 11 patients. Cholangitis was frequent (9/11 cases). Cholestasis was observed in eight cases. Pseudo-glandular pattern was present in only one case but without zonal repartition. Characteristic pathological signs of acute hepatitis E were severe intralobular necrosis, polymorph inflammation, and acute cholangitis with numerous neutrophils. PMID- 17333268 TI - Expression of sex steroid hormone receptors in C cell hyperplasia and medullary thyroid carcinoma. AB - Previous studies have shown that C cells are twice as numerous in male than in female thyroids and that C cell hyperplasia (CCH) is much more frequent in men. These findings suggest regulation involving sex steroid hormones through the expression of sex steroid hormone receptors on C cells. To investigate this hypothesis, we performed an immunohistochemical study of estrogen receptors alpha (ER alpha) and beta (ER beta), progesterone receptors (PR), and androgen receptors (AR) on specimens from a series of 40 patients operated on for a medullary thyroid carcinoma (MTC; n=28; female 18, male 10) and/or CCH (n=19; female 6, male 13). ER beta was the only receptor to be consistently expressed in CCH (100%) and MTC (96.5%), whereas ER alpha was never expressed. PR and AR were rarely expressed in MTC (7 and 14%, respectively). AR was expressed in half the CCH cases (53%), with a trend to male predominance (61% in men vs 33% in women). Our study is the first to describe ER beta expression in CCH. In addition, our findings suggest that CCH, and possibly MTC, might be influenced by sex steroid hormones, namely, estrogens and androgens, through the expression of ER beta and AR on C cells. PMID- 17333269 TI - A CIAS1 mutation in a Japanese girl with familial cold autoinflammatory syndrome. PMID- 17333267 TI - Expression of aberrant mucins in lobular carcinoma with histiocytoid feature of the breast. AB - The clinicopathological profiles of histiocytoid carcinoma of the breast have not been well examined because of their rarity and heterogenous groups of ductal and lobular origin. A large foamy or granular cytoplasm of histiocytoid carcinoma was characterized by abundant mucin, but the properties of mucin in histiocytoid carcinoma have also not been well investigated. We selected eight cases of histiocytoid features of invasive lobular carcinoma (HLC) and compared with 14 age- and tumor size-matched cases of classical invasive lobular carcinoma (CLC). Mucin profiles were significantly different between the two groups: a fair number of HLC cases were immunopositive for MUC2 and MUC5AC (75 and 50%, respectively); in contrast, almost all CLC cases showed both as negative. Both groups were immunopositive for MUC1 and negative for MUC4 and MUC6. The prognosis of HLC was significantly worse than CLC; HLC showed shorter disease-free time than CLC (p=0.0262). In particular, HLC with MUC2 and MUC5AC expressions showed significantly shorter disease-free time and survival time than lobular carcinoma without the expressions of MUC2 and MUC5AC (p=0.0055 and p=0.0060, respectively). Therefore, the expression of 'non-mammary mucins', such as MUC2 and MUC5AC in HLC, is characteristic and indicates the more malignant transformation of tumor cells and poorer prognosis. PMID- 17333270 TI - Pneumomediastinum: a rare complication of anorexia nervosa in children and adolescents. A case study and review of the literature. AB - Spontaneous pneumomediastinum is uncommon in paediatric practice. We describe two cases of spontaneous pneumomediastinum in a child and an adolescent with anorexia nervosa. Thorough investigation failed to reveal any underlying cause for secondary pneumomediastinum. Pneumomediastinum in anorexia nervosa can be caused by not only elevated intrathoracic pressures, but also by the poor quality of the alveolar walls due to malnutrition. The incidence of spontaneous pneumomediastinum in anorexia nervosa is probably higher than that recorded, since it resolves spontaneously and, therefore, it can remain undetected. We conclude that it is our considered opinion that malnutrition associated with anorexia nervosa predisposes for spontaneous pneumomediastinum due to weakness of the alveolar wall and the loss of connective tissue. PMID- 17333271 TI - Incidence of late vitamin K deficiency bleeding in newborns in the Netherlands in 2005: evaluation of the current guideline. AB - Vitamin K prophylaxis is recommended to prevent the hazard of haemorrhage caused by vitamin K deficiency in newborns. The present Dutch guideline recommends 1 mg of vitamin K(1) orally at birth, followed by a daily dose of 25 microg of vitamin K(1) from 1 to 13 weeks of age for breastfed infants. Since the introduction of this prophylaxis, the incidence of vitamin K deficiency bleeding (VKDB) has decreased; however, late VKDB is still reported. From 1 January to 31 December 2005, a nationwide active surveillance was performed by the Netherlands Paediatric Surveillance Unit (NSCK) to study the current incidence and aetiology of late VKDB in infants. Six cases could be validated as late VKDB: all were breastfed, one fatal idiopathic intracranial haemorrhage at the age of 5 weeks and five bleedings secondary to an underlying cholestatic liver disease between the age of 3 and 7 weeks. The total incidence of late VKDB and idiopathic late VKDB was calculated to be 3.2 (95% CI: 1.2-6.9) and 0.5 (95% CI: 0-2.9) per 100,000 live births, respectively. With the current Dutch guideline, idiopathic late VKDB is rare but late VKDB secondary to cholestasis still occurs in breastfed infants. Doubling the daily dose of vitamin K(1) to 50 microg, as is comparable to formula-feeding, may possibly prevent VKDB in this group. Further research, however, is needed to prove this hypothesis. PMID- 17333272 TI - A cross-sectional study of dietary habits and lipid profiles. The Rivas Vaciamadrid study. AB - The relations between dietary habits and serum lipids have been firmly established in adults. In children, this relation has been less extensively studied. We have assessed the relations between dietary components, including the different types of fatty acids (saturated, polyunsaturated and monounsaturated) and serum lipids and apolipoproteins in a group of 673 6-year-old children of the town of Rivas-Vaciamadrid, Spain. Children in the highest tertile of total fat consumption, when compared with children in the lowest tertile, had higher mean levels of total cholesterol (188.3 mg/dl vs. 146.8 mg/dl), triglycerides (56.7 mg/dl vs. 51.3 mg/dl), LDL cholesterol (120.7 mg/dl vs. 92.6 mg/dl), HDL cholesterol (56.2 mg/dl vs. 54.5 mg/dl) and apolipoprotein B (86.8 mg/dl vs. 62.9 mg/dl). When compared with children in the lowest tertile, children in the highest tertile of saturated fat consumption had significantly higher mean levels of total cholesterol (206.3 mg/dl vs. 151.8 mg/dl), LDL cholesterol (140.6 mg/dl vs. 95.1 mg/dl) and apolipoprotein B (99.2 mg/dl vs. 64.3 mg/dl) and lower mean levels of HDL cholesterol (53.5 mg/dl vs. 57.5 mg/dl), whereas children in the highest tertile of monounsaturated fat consumption had significantly higher mean levels of HDL cholesterol (56.5 mg/dl vs. 51.8 mg/dl) and lower levels of total cholesterol (133.2 mg/dl vs. 201.6 mg/dl), LDL cholesterol (93.1 mg/dl vs. 137.5 mg/dl) and apolipoprotein B (68.6 mg/dl vs. 94.9 mg/dl) than children in the lowest tertile. No statistically significant relation between polyunsaturated fat and lipid levels was found. We have found a strong association between diet composition and lipid and apolipoprotein levels in 6-year-old children. Our findings strengthen the role of monounsaturated fatty acid consumption as a part of a healthy diet in childhood. PMID- 17333274 TI - Consequences of Directive 2001/20/EC for investigator-initiated trials in the paediatric population--a field report. AB - On 4 April 2001, the European Parliament and Council enacted Directive 2001/20/EC, which had to be implemented in the national law of the European Union member states by May 2004. Its aim was to improve the quality of clinical trials and to assure the safety and well-being of trial subjects. We recently initiated the first paediatric investigator-initiated trial (IIT) at the University Hospital of Cologne according to Directive 2001/20/EC. This field report demonstrates the consequences and implications of the directive for paediatric IITs. Based on our experience, we agree that Directive 2001/20/EC improves the quality of clinical trials and assures the safety and well-being of trial subjects. However, at the same time, performing an IIT according to the new requirements is nearly impossible for clinicians and academic researchers without cooperating with expensive specialised experts, such as project managers, statisticians, data managers, pharmacists and monitors. Therefore, it is absolutely mandatory that financial support for paediatric IITs be adapted and increased in order to be able to meet the new requirements and obligations. Regulation (EC) No 141/2000 on orphan medicinal products and the recently adopted regulation on medicinal products for paediatric use (Paediatric Regulation) are important steps in improving clinical research in children. However, both regulations mainly encourage clinical research carried out by the pharmaceutical industry, whereas paediatric IITs are not in the scope of this legislation. We need to develop new concepts for funding to ensure future paediatric IITs, for example through specific grants from the European Union or member states. PMID- 17333273 TI - Outcome of extremely low birth weight survivors at school age: the influence of perinatal parameters on neurodevelopment. AB - Extremely low birth weight (ELBW) is associated with impaired neurodevelopmental outcome in infancy. Information on the long-term cognitive and neurological consequences of ELBW is scarce. We aimed to identify the perinatal and neonatal factors of ELBW infants associated with adverse cognitive and neurological outcome at school age. A regional cohort of 135 ELBW infants born between 1993 and 1998 was prospectively evaluated at 3, 6, 12, and 18 months postmenstrual age and at yearly intervals up to age 10 years. The comprehensive follow-up programme for high-risk infants included neurological examinations and psychometric evaluations. According to the overall results of these tests, children were classified as either being normal or having minor or major impairment. At a mean age of 8.4 (SD: 1.6) years, 43% of children had survived without any impairment. Minor impairment was diagnosed in 39% and major impairment in 18% of assessed children. The proportion of disabled school children rose with decreasing gestational age. The following neonatal complications were significant risk factors for developing major or minor impairment at school age: an increase in head circumference < 6 mm per week (OR 4.0, 95% CI: 1.1-14.8), parenteral nutrition > or = 6 weeks (OR 2.5, 95% CI: 1.1-6.0), and mechanical ventilation > 14 days (OR 2.3, 95% CI: 1.0-5.1). High-grade intraventricular haemorrhage (IVH) and/or PVL (OR 13.3, 95% CI: 4.0-44.9), neonatal seizures (OR 5.2, 95% CI: 1.2 22.4) and bowel perforation, and/or necrotizing enterocolitis (OR 4.4, 95% CI: 1.1-17.0) were significant risk factors for developing major impairment. In spite of the relatively large proportion of normal children, ELBW remains an important risk factor for neurodevelopmental impairment at school age. Thus, measures to prevent complications such as necrotizing enterocolitis, cerebral haemorrhage, and undernutrition remain important goals for neonatal intensive care. PMID- 17333275 TI - Severe gastrointestinal vasculitis in Henoch-Schoenlein purpura: pathophysiologic mechanisms, the diagnostic value of factor XIII, and therapeutic options. PMID- 17333277 TI - An unidentified epi-epithelial myxosporean in the intestine of gilthead sea bream Sparus aurata L. AB - In the course of experimental infections of gilthead sea bream Sparus aurata with the myxozoan Enteromyxum leei, stages of an unidentified myxozoan were observed attached to the intestinal brush border of some fish. Infection levels of the parasite, which was named "epi-epithelial myxosporean" (EEM) were recorded, and its structure was studied by light microscopy (LM) and electron microscopy (EM). In situ hybridisation (ISH) probes specific for E. leei were developed and used to differentiate between the two parasites. The EEM parasite was observed only in epi-epithelial position on the intestine mucosa and never in any of the other tissues studied (kidney and gall bladder). Prevalence was variable, with values reaching 40.2%. With transmission EM, trophozoites displayed pseudopodia-like projections inserted in between the enterocyte microvilli, producing an intimate interface. No mucosal histopathology that could be attributed to the myxozoan was found. EEM stages did not stain with the E. leei-specific ISH probes. From the results of the LM, EM and ISH studies, we conclude that the EEM parasite found in gilthead sea bream intestine in both Mediterranean and Red Sea sites is a coelozoic myxosporean, distinct from E. leei. PMID- 17333278 TI - Isolation and molecular characterization of Toxoplasma gondii strains from different hosts in Iran. AB - Toxoplasma gondii is one of the most prevalent protozoan parasites in Iran. This study was aimed to isolate T. gondii from a variety of hosts and to genetically analyze the parasite isolates. The prevalence of T. gondii in different animal hosts was assessed in two provinces of Iran, Tehran and Mazandaran in the central and northern parts, respectively. The latex agglutination (LA) test was carried out, and antibodies were found in 24 out of 105 sheep, 5 out of 35 goats, 23 out of 45 free-ranging chickens (Gallus domesticus), 2 out of 13 ducks (Anas spp.), and two of four stray cats (Felis domesticus). T. gondii was isolated by bioassay in mice from four sheep, six chickens, one duck, two cats, and three human samples. Genotyping of these 16 isolates was performed using Multiplex PCR for five microsatellite markers and GRA6 gene sequence analysis. The results indicated that the studied isolates consisted of only two genotypes, II and III, with no evidence of type 1 or mixed genotypes. PMID- 17333279 TI - High diversity of plastidial promoters in Arabidopsis thaliana. AB - Arabidopsis thaliana is well established as a model plant in modern plant biology. However, remarkably few details are known about plastidial promoters in Arabidopsis. Here, we report on the identification and analyses of sequences at transcription start sites of selected genes. The genes encoded by the plastome of higher plants are transcribed by a plastid-encoded (PEP) and a nuclear-encoded RNA plastid polymerase (NEP). To discriminate between NEP and PEP promoters we compared the 5'-ends of transcripts from chlorophyll-deficient Arabidopsis plants, which were grown on prokaryotic translation inhibitor spectinomycin to inhibit biosynthesis of PEP, with those of untreated plants. Using 5'-RACE combined with enzymatic treatment of RNAs to recognize primary and secondary 5' ends, we unambiguously identified transcription initiation sites of the Arabidopsis accD, atpB, atpI, rpoB, rps4, rps15, and ycf1 genes. Comparison of plastidial promoters from tobacco and Arabidopsis revealed a high diversity, which may also apply to other plants. Furthermore, the diversity in individual promoter usage in different plants suggests that there are species-specific solutions for attaining control over gene expression in plastids. PMID- 17333281 TI - A mutation in the lipase H (LIPH) gene underlie autosomal recessive hypotrichosis. AB - Hereditary hypotrichosis is a rare autosomal recessive disorder characterized by sparse hair on scalp and rest of the body of affected individuals. Two forms of such hypotrichosis LAH and AH have been mapped on chromosome 18q12.1 and 3q27, respectively. Mutations in desmogelin 4 (DSG4) gene have been reported to underlie LAH. Recently, a deletion mutation in Lipase H (LIPH) gene, located at AH locus, has been identified in two ethnic groups of Russian population. In the present study, a four generation Pakistani family with AH phenotype has been mapped to chromosome 3q27. Sequence analysis of candidate gene LIPH revealed a novel five base pair deletion mutation (c.346-350delATATA) in exon 2 of the gene leading to frameshift and downstream premature termination codon. The mutation reported in the family, presented here, is the second mutation identified in LIPH gene. The identification of a genetic defect in LIPH suggests that this enzyme regulates hair growth. PMID- 17333280 TI - Cytoplasmatic post-transcriptional regulation and intracellular signalling. AB - Studies of intracellular signalling have traditionally focused on regulation at the levels of initiation of transcription on one hand, and post-translational regulation on the other. More recently, it is becoming apparent that the post transcriptional level of gene expression is also subject to regulation by signalling pathways. The emphasis in this review is on short-term regulation of mRNAs at the levels of degradation and frequency of translation. Interplay between the mRNA translation and degradation machineries and mainly the TOR, stress-induced MAP kinase (SAPK), and DNA damage checkpoint pathways is discussed. Since a large fraction of the molecular mechanisms has been dissected using molecular genetics methods in yeast, most of the examples in this review are from budding and fission yeast. Some parallels are drawn to plant and animal cells. This review is intended for those more familiar with intracellular signalling, and who realise that post-transcriptional regulation may be an underemphasised level of signalling output. PMID- 17333282 TI - Loss of SLC38A5 and FTSJ1 at Xp11.23 in three brothers with non-syndromic mental retardation due to a microdeletion in an unstable genomic region. AB - Using high resolution X chromosome array-CGH we identified an interstitial microdeletion at Xp11.23 in three brothers with moderate to severe mental retardation (MR) without dysmorphic features. The extent of the deletion was subsequently delineated to about 50 kb by regular PCR and included only the SLC38A5 and FTSJ1 genes. The loss of the FTSJ1 MR gene in males is expected to result in the observed phenotype but the contribution of the deletion of the solute carrier SLC38A5 gene is less clear. Their mother also carries the deletion and completely inactivates the aberrant X chromosome. Interestingly, the distal breakpoint is situated within a 200 kb SSX repeat region that appears to stimulate recombination since subtle copy number changes often occur at this location and it is frequently involved in translocations in tumours. Since this apparent SSX unstable structure is flanked proximally by FTSJ1 and PQBP1, subtle deletions or duplications at this location would be expected to cause MR, as in our family. So far, we have screened a cohort of 300 patients but did not find additional aberrations at the FTSJ1 locus indicating that the frequency is likely to be low. PMID- 17333283 TI - Candidate SNPs for a universal individual identification panel. AB - Single nucleotide polymorphisms (SNPs) are likely in the near future to have a fundamental role both in human identification and description. However, because allele frequencies can vary greatly among populations, a critical issue is the population genetics underlying calculation of the probabilities of unrelated individuals having identical multi-locus genotypes. Here we report on progress in identifying SNPs that show little allele frequency variation among a worldwide sample of 40 populations, i.e., have a low F(st), while remaining highly informative. Such markers have match probabilities that are nearly uniform irrespective of population and become candidates for a universally applicable individual identification panel applicable in forensics and paternity testing. They are also immediately useful for efficient sample identification/tagging in large biomedical, association, and epidemiologic studies. Using our previously described strategy for both identifying and characterizing such SNPs (Kidd et al. in Forensic Sci Int 164:20-32, 2006), we have now screened a total of 432 SNPs likely a priori to have high heterozygosity and low allele frequency variation and from these have selected the markers with the lowest F(st) in our set of 40 populations to produce a panel of 40 low F(st), high heterozygosity SNPs. Collectively these SNPs give average match probabilities of less than 10(-16) in most of the 40 populations and less than 10(-14) in all but one small isolated population; the range is 2.02 x 10(-17) to 1.29 x 10(-13). These 40 SNPs constitute excellent candidates for the global forensic community to consider for a universally applicable SNP panel for human identification. The relative ease with which these markers could be identified also provides a cautionary lesson for investigations of possible balancing selection. PMID- 17333285 TI - Food supply modifies the trade-off between past and future reproduction in a sexual parasite-host system (Rana esculenta, Rana lessonae). AB - Life history theory is concerned with the costs of survival, growth and reproduction under different ecological conditions and the allocation of resources to meet these costs. Typical approaches used to address these topics include manipulation of food resources, followed by measures of subsequent reproductive traits, and measures of the relationship between current and future reproductive investment. Rarely, however, do studies test for the interaction of past investment, present resource availability and future investment simultaneously. Here, we investigate this interaction in females of a sexual parasite-host system consisting of the hybridogenetic frog Rana esculenta (E) and one of its parental species Rana lessonae (L). We kept females from each of two groups (with or without previous reproduction) under two food treatments (low or high) and regularly recorded their growth as well as their body condition and hormone titres as measures of future reproductive condition. After keeping them in hibernation until the following spring, we exposed the females to males, recorded whether they spawned or not and related this response to their condition in the previous autumn. Past reproduction negatively affected growth during summer and condition during autumn which, in turn, reduced the following year's reproductive output. These costs of previous reproduction were less pronounced under the high than under the low food treatment and lower in R. lessonae than in R. esculenta. Increasing food supply improved reproductive condition more in L than in E females. These species differences in reproductive costs and food requirements provide a mechanistic explanation for why E females skip annual reproduction almost twice as often as L females. Since R. esculenta is a sexual parasite that depends on R. lessonae for successful reproduction, these species specific life history patterns not only affect individual fitness but also the spatial structure and temporal dynamics of mixed LE populations. PMID- 17333284 TI - Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy. AB - Transforming growth factor beta-1 (TGFB1) may influence asthma by modulating allergic airway inflammation and airway remodeling. The role of single nucleotide polymorphisms (SNPs) of TGFB1 in asthma remains inconclusive. We examined TGFB1 SNPs in relation to asthma risk and degree of atopy among 546 case-parent triads, consisting of asthmatics aged 4-17 years and their parents in Mexico City. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped five TGFB1 SNPs, including two known functional SNPs [C-509T (rs1800469), T869C (rs1982073)] and three others (rs7258445, rs1800472, rs8179181), using TaqMan and Masscode assays. We analyzed the data using log-linear and polytomous logistic methods. Three associated SNPs, including the two known functional SNPs, were statistically significantly related to asthma risk. Individuals carrying the T allele of C-509T had an increased risk of asthma [relative risk (RR)=1.42, 95% confidence interval (CI)=1.08-1.87 for one copy; RR (95%CI)=1.95 (1.36-2.78) for two copies]. For T869C, the RRs (95%CI) were 1.47 (1.09-1.98) for one and 2.00 (1.38-2.90) for two copies of the C allele. Similar results were found for rs7258445. The haplotype containing all three risk alleles conferred an increased risk of asthma (RR=1.48, 95% CI=1.11-1.95 for one copy; RR=1.77, 95% CI=1.22-2.57 for two copies). These three SNPs were also related to the degree of atopy. This largest study to date of genetic variation in TGFB1 and asthma and atopy adds to increasing evidence for a role in these disorders. PMID- 17333286 TI - Leaf gas exchange and water status responses of a native and non-native grass to precipitation across contrasting soil surfaces in the Sonoran Desert. AB - Arid and semi-arid ecosystems of the southwestern US are undergoing changes in vegetation composition and are predicted to experience shifts in climate. To understand implications of these current and predicted changes, we conducted a precipitation manipulation experiment on the Santa Rita Experimental Range in southeastern Arizona. The objectives of our study were to determine how soil surface and seasonal timing of rainfall events mediate the dynamics of leaf-level photosynthesis and plant water status of a native and non-native grass species in response to precipitation pulse events. We followed a simulated precipitation event (pulse) that occurred prior to the onset of the North American monsoon (in June) and at the peak of the monsoon (in August) for 2002 and 2003. We measured responses of pre-dawn water potential, photosynthetic rate, and stomatal conductance of native (Heteropogon contortus) and non-native (Eragrostis lehmanniana) C(4) bunchgrasses on sandy and clay-rich soil surfaces. Soil surface did not always amplify differences in plant response to a pulse event. A June pulse event lead to an increase in plant water status and photosynthesis. Whereas the August pulse did not lead to an increase in plant water status and photosynthesis, due to favorable soil moisture conditions facilitating high plant performance during this period. E. lehmanniana did not demonstrate heightened photosynthetic performance over the native species in response to pulses across both soil surfaces. Overall accumulated leaf-level CO(2) response to a pulse event was dependent on antecedent soil moisture during the August pulse event, but not during the June pulse event. This work highlights the need to understand how desert species respond to pulse events across contrasting soil surfaces in water-limited systems that are predicted to experience changes in climate. PMID- 17333287 TI - Low stocks of coarse woody debris in a southwest Amazonian forest. AB - The stocks and dynamics of coarse woody debris (CWD) are significant components of the carbon cycle within tropical forests. However, to date, there have been no reports of CWD stocks and fluxes from the approximately 1.3 million km(2) of lowland western Amazonian forests. Here, we present estimates of CWD stocks and annual CWD inputs from forests in southern Peru. Total stocks were low compared to other tropical forest sites, whether estimated by line-intercept sampling (24.4 +/- 5.3 Mg ha(-1)) or by complete inventories within 11 permanent plots (17.7 +/- 2.4 Mg ha(-1)). However, annual inputs, estimated from long-term data on tree mortality rates in the same plots, were similar to other studies (3.8 +/- 0.2 or 2.9 +/- 0.2 Mg ha(-1) year(-1), depending on the equation used to estimate biomass). Assuming the CWD pool is at steady state, the turnover time of coarse woody debris is low (4.7 +/- 2.6 or 6.1 +/- 2.6 years). These results indicate that these sites have not experienced a recent, large-scale disturbance event and emphasise the distinctive, rapid nature of carbon cycling in these western Amazonian forests. PMID- 17333288 TI - Variability of the start of the growing season in Fennoscandia, 1982-2002. AB - Fennoscandia is characterized by a large degree of climatic diversity. Vegetation phenology may respond differently to climate change according to the climatic gradients within the region. To map the annual and spatial variability of the start of the growing season (SOS) in Fennoscandia, the twice-monthly GIMMS-NDVI satellite dataset was used. The data set has an 8 x 8 km(2) spatial resolution and covers the period from 1982 to 2002. The mapping was done by applying pixel specific threshold values to the NDVI data. These threshold values were determined form surface phenology data on birch (Betula sp.). Then, we produced NDVI based maps of SOS for each of the 21 years. Finally, the time differences between the SOS and the last day of snow cover, as well as dates of passing different temperatures, were analyzed for 21 meteorological stations. The analyses showed that 1985 was the most extreme year in terms of late SOS. In terms of early SOS, the year 1990 was by far the most extreme. Locally, the SOS has an average range of 1 month between the earliest and latest recorded SOS, with a trend towards a bigger range in the oceanic parts. The results indicate that a 1 degrees C increase in spring temperatures in general corresponds to an advancement of 5-6 days in SOS. However, there is a clear trend according to the degree of oceanity, with a 1 degrees C increase in the most oceanic parts corresponding roughly to 7-9 days earlier SOS, compared to less than 5 days earlier in the continental parts. PMID- 17333289 TI - The sensitivity of tree growth to air mass variability and the Pacific Decadal Oscillation in coastal Alabama. AB - This study investigates the relationship between tree growth and air mass type variability, using the spatial synoptic classification (SSC) in a bottomland slash pine forest in coastal Alabama (USA). The use of an air mass approach in dendroclimatology is somewhat unconventional and has not been fully explored. However, we believe that it may be useful because the air mass approach represents a holistic and comprehensive measure of surface conditions. Cores from 36 slash pines (Pinus elliotti) were extracted and ring widths were measured to the nearest 0.01 mm. The cores were then cross-dated and a standardized ring index series was established. Relationships were explored between the index series and several climate variables and teleconnections. The index series showed significant relationships with SSC air mass types and SSC air mass ratios, but insignificant results with teleconnections. Specifically the Dry Tropical air mass type was negatively correlated with tree growth while Moist Moderate was positively correlated. Concomitantly, Dry Tropical : Moist Moderate, Dry Tropical : Moist Tropical, and Dry Moderate : Moist Moderate air mass ratios also showed negative correlations. Positive Pacific Decadal Oscillation (PDO) sea surface temperatures were also associated with significant moisture and air mass variability in the region, although the PDO did not have a significant relationship with tree growth. The significance between SSC air mass variability and tree growth in the humid subtropical climate of coastal Alabama has favorable implications for dendroclimatological research in drier environments where trees are more sensitive to climatic variables. PMID- 17333290 TI - Paradox: increased blood perfusion to the face enhances protection against frostbite while it lowers wind chill equivalent temperatures. AB - A model of facial heat exchange in cold and windy environments is presented. The tissue is depicted as a hollow cylinder and the model includes heat conduction and heat transport by blood circulation from the warmer core. A steady-state solution facilitating the estimation of wind chill equivalent temperature (WCET) as a function of the effective wind velocity, air temperature and blood perfusion rate was obtained. The results quantify and demonstrate the elevation of skin temperatures caused by increased flow of warmer blood from the inner core to the face. Elevated facial temperatures, while enhancing protection against frostbite and other cold-related injuries, also increase heat loss to the colder environment. Paradoxically, such elevated facial temperatures cause WCETs, as estimated by the prevailing definition, to attain lower rather than higher values, indicating, in fact, increased risk of frostbite. The results of this study should be useful in understanding and quantifying the effects of blood perfusion in protection against cold-related injuries. They should also be considered in the re-evaluation and re-formulation of the concept of wind chill, which has been a useful cold weather indicator for decades. PMID- 17333292 TI - Real-time broad-range PCR versus blood culture. A prospective pilot study in pediatric cancer patients with fever and neutropenia. AB - MATERIALS AND METHODS: In a pilot study, results of real-time broad-range (16S rRNA) polymerase chain reaction (PCR) performed on 45 blood samples of pediatric cancer patients with fever and neutropenia were compared with blood culture results. RESULTS: The PCR assay used, having proven a high sensitivity in artificially spiked blood samples, was positive in only three of ten blood culture-positive samples, and it was positive in 10 of 35 (29%) culture-negative samples. CONCLUSION: This broad-range PCR assay, which may identify not-grown bacteria potentially contributing to fever, needs improvement in sensitivity, and different reasons for positive PCR in negative blood culture samples need to be assessed before clinical application. PMID- 17333293 TI - Developing supportive care for family members of people with lung cancer: a feasibility study. AB - PURPOSE: Families provide crucial support, yet their own needs often go unrecognised and, as a consequence, remain unmet. The purpose of this study was to evaluate a newly developed supportive intervention for family members of patients with lung cancer. MATERIALS AND METHODS: A consecutive convenience sample of 25 family members of people with lung cancer received an individualised supportive intervention from a support nurse over a period of 12 weeks. This involved in-depth assessment followed up with a tailored plan of ongoing support to address informational, emotional, social and practical needs. A concurrent mixed method design explored perceptions and outcomes of those receiving the intervention and assess its appropriateness, acceptability and feasibility. Data were collected through a semi structured telephone interview with family members, and support nurses maintained a contact log. A questionnaire addressed emotional well-being [general health questionnaire (GHQ-12)], quality of life [quality of life family version (Family QoL)] and needs for care [family inventory of needs (FIN)]-at baseline and week 12. RESULTS: Family members perceived they had derived benefit from the intervention. Certain elements clearly emerged as important for participants, including being listened to by someone who could facilitate emotional expression, being provided with individually tailored information and receiving practical help and advice. Outcomes mapped to five main areas: information needs, communication between family members, emotional well being, being supported and facilitating family member's role. There was a trend for more needs to be met and quality of life and emotional well-being to improve at week 12. CONCLUSION: This study has demonstrated that a supportive intervention for family members of patients with lung cancer can be delivered to good effect by experienced cancer nurses. The active components of the intervention have been distinguished and provide the basis for development of a larger sufficiently powered trial. PMID- 17333294 TI - Association of complementary methods with quality of life and life satisfaction in patients with gynecologic and breast malignancies. AB - GOALS OF WORK: In gynecological oncology, there is growing interest in the use of complementary and alternative medicine (CAM) methods. The lack of data regarding side effects, the lack of any survival advantages, and the costs of these methods appear to have no influence on patients' decisions on whether to use CAM. Our interest was to evaluate the association between CAM use and the patients' quality of life/life satisfaction (QoL/LS). MATERIALS AND METHODS: One thousand thirty women with breast cancer of gynecologic malignancies were asked to participate in this study, which included a questionnaire and a personal interview on CAM. User status was compared with the patient's own description of her QoL/LS and with the cancer type. MAIN RESULTS: CAM was used by 48.7% of all women (n = 502). Breast cancer patients stated that they used CAM in 50.1% and women with gynecological cancer in 44.0%. The use of mistletoe was widespread (77.3%) and was more often seen in breast cancer patients than in gynecological cancer patients (74.4% vs 67.0%). CAM users less frequently stated an overall deterioration of their health status (35.1%) compared to nonusers (50.1%). CAM use resulted in a stated improvement in family conditions (6%) in comparison with the nonusers (2%). CONCLUSIONS: With regard to patients' perception of health status, CAM use is associated with a better coping with their disease. Most other categories of LS are not affected by CAM use. Patient-oriented information comparing standard therapies with CAM methods should be made widely available, and patients' expectations of CAM use should be discussed between the physician and the patient. PMID- 17333295 TI - Decreases in pain at rest and movement-related pain during zoledronic acid treatment in patients with bone metastases due to breast or prostate cancer: a pilot study. AB - BACKGROUND: In patients with bone metastases, pain may be absent or moderate at rest, but may be exacerbated by different movements or positions. No study has evaluated separately pain at rest and on movement in patients with bone metastases undergoing treatment with zoledronic acid (ZA). AIM: The aim of this prospective observational study was to evaluate the reduction in intensity of pain at rest and in movement-related pain after treatment with up to six infusions of ZA 4 mg every 28 days in patients with painful bone metastases due to breast or prostate cancer cared for at the Oncological Units and Pain Therapy and Palliative Care Unit of the NCI of Milano. MATERIALS AND METHODS: Pain was assessed by a six-level verbal rating scale (0-5 score) at baseline and on each infusion as well as at follow-up visits (2 weeks after every infusion). The two main endpoints (estimated reduction in pain and movement-related pain) were defined as the difference between the baseline score and the average of all the post-treatment scores for each patient. To allow for the potential confounding effect of analgesic consumption, patients without any increase in analgesic consumption during zoledronic acid treatment were also analyzed as a separate subgroup. RESULTS: Forty-eight patients with breast (34) or prostate cancer (14) were enrolled. At baseline, 100% of the patients had pain on movement, in 65% of them, the intensity ranged from moderate to very severe, in 61% of the patients, the intensity of pain on movement was higher than the intensity of pain at rest (average difference 0.89; 95% CI, 0.5-1.30). The estimated mean intensity reduction of pain at rest and on movement was: (a) 0.62 (95% CI, 0.28-0.98) and 0.79 (95% CI, 0.43-1.14), respectively, during the first 90 days of ZA treatment; (b) 0.59 (95% CI, 0.23-0.96) and 0.86 (95% CI, 0.49-1.23), respectively, during the entire treatment and follow-up period. Analgesic consumption decreased or was stable on average in 31 and 27%, respectively, of available follow-up data. In the 14 patients with decreased or stable analgesic consumption, pain reduction was 0.61 and 1.01, respectively. CONCLUSIONS: In this study, at baseline, all the patients with painful bone metastases experience movement-related pain, and during zoledronic acid treatment, a decrease for both pain at rest and on movement was obtained. PMID- 17333296 TI - Prospective evaluation of fatigue during a course of curative radiotherapy for localised prostate cancer. AB - PURPOSE: To prospectively evaluate radiation-induced fatigue among patients undergoing curative radiotherapy at the Toronto Sunnybrook Regional Cancer Centre using two different instruments. MATERIALS AND METHODS: Consecutive consenting English speaking men receiving curative radiotherapy for localised prostate cancer were enrolled in a prospective ethics board approved study. We used an 11 questions fatigue questionnaire (FQ) based on a modified FACT-AN questionnaire and the 2 questions of the fatigue pictogram (FP) to record patients' responses weekly during treatment. The 11 FQ items were summed to calculate a fatigue scale (FS). The proportion and 95% confidence interval for each FQ and FP item and mean FS was calculated at baseline, week 3 and week 6. Chi-squared tests or analysis of variance f-tests were used to compare treatment groups and paired t-tests to compare baseline to week 6. A linear mixed model was used to compare the mean FS for treatment groups across time. RESULTS: From June 2000 to June 2003, we enrolled 130 patients. Fifty-one received conformal radiotherapy to the prostate (CRT), 46 received whole pelvis and prostate boost radiotherapy (WP+PB) and 33 received post prostatectomy radiotherapy to the prostate bed (PBRT). At baseline, 39% (30-47%) reported some fatigue for the FQ and 60% (52-68%) for the FP tiredness item. As treatment progressed, the mean fatigue increased significantly. The FP tiredness item best differentiated between treatment groups (p = 0.04 at week 6) compared to the FQ tiredness item or FS. Those receiving irradiation to smaller volumes (CRT or PBRT) reported lower FS scores than those treated to larger volumes (WP+PB) across time. CONCLUSIONS: The pictogram was better than the questionnaire in differentiating between treatment groups. The pictogram could be used to screen and monitor patients with baseline fatigue for interventional studies in a busy clinic. PMID- 17333297 TI - Reluctance to disclose difficult diagnoses: a narrative review comparing communication by psychiatrists and oncologists. AB - INTRODUCTION: National guidance in most medical specialties supports the full and open disclosure of diagnoses to patients. RESULTS: Surveys show that most patients want to know their diagnosis, whether it is medical or psychiatric, and a substantial proportion want to know detailed prognostic information. In the past, oncologists have been criticised for failing to reveal a diagnosis of cancer to patients in a sensitive and timely manner. Over the last 30 years, there is evidence that this practice has improved. Yet, clinicians still have difficulty when the diagnosis is not certain, when the prognosis is unfavourable, and when relatives request "not to tell." All of these influences are present in mental health settings. DISCUSSION: Psychiatrists and general practitioners may be equally reluctant to reveal difficult diagnoses and prognoses of conditions such as schizophrenia and dementia. The reluctance to reveal a difficult diagnosis may be a routine, but little acknowledged the aspect of medical care that should be incorporated into undergraduate and postgraduate education and openly discussed during peer group supervision. PMID- 17333298 TI - Water transfer via ectomycorrhizal fungal hyphae to conifer seedlings. AB - Little is known about water transfer via mycorrhizal hyphae to plants, despite its potential importance in seedling establishment and plant community development, especially in arid environments. Therefore, this process was investigated in the study reported in this paper in laboratory-based tripartite mesocosms containing the shrub Arctostaphylos viscida (manzanita) and young seedlings of sugar pine (Pinus lambertiana) and Douglas-fir (Pseudotsuga menziesii). The objectives were to determine whether water could be transported through mycorrhizal symbionts shared by establishing conifers and A. viscida and to compare the results obtained using two tracers: the stable isotope deuterium and the dye lucifer yellow carbohydrazide. Water containing the tracers was added to the central compartment containing single manzanita shrubs. The fungal hyphae were then collected as well as plant roots from coniferous seedlings in the other two compartments to determine whether water was transferred via fungal hyphae. In addition, the length of the hyphae and degree of mycorrhizal colonisation were determined. Internal transcribed spacer-restriction fragment length polymorphism (ITS-RFLP) analysis was used to identify the fungal species involved in dye (water) transfer. Results of the stable isotope analysis showed that water is transferred via mycorrhizal hyphae, but isotopically labelled water was only detected in Douglas-fir roots, not in sugar pine roots. In contrast, the fluorescent dye was transported via mycorrhizal hyphae to both Douglas-fir and sugar pine seedlings. Only 1 of 15 fungal morphotypes (identified as Atheliaceae) growing in the mesocosms transferred the dye. Differences were detected in the water transfer patterns indicated by the deuterium and fluorescent dye tracers, suggesting that the two labels are transported by different mechanisms in the same hyphae and/or that different fungal taxa transfer them via different routes to host plants. We conclude that both tracers can provide information on resource transfer between fungi and plants, but we cannot be sure that the dye transfer data provide accurate indications of water transfer rates and patterns. The isotopic tracer provides more direct indications of water movement and is therefore more suitable than the dye for studying water relations of plants and their associated mycorrhizal fungi. PMID- 17333299 TI - Ab initio simulations of Cu binding sites on the N-terminal region of prion protein. AB - The human prion protein binds Cu2+ ions in the octarepeat domain of the N terminal tail up to full occupancy at pH 7.4. Recent experiments have shown that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square-planar configuration. By using first principle ab initio molecular dynamics simulations of the Car-Parrinello type, the coordination of copper to the binding sites of the prion protein octarepeat region is investigated. Simulations are carried out for a number of structured binding sites. Results for the complexes Cu(HGGGW)(wat), Cu(HGGG), and [Cu(HGGG)]2 are presented. While the presence of a Trp residue and a water molecule does not seem to affect the nature of the copper coordination, high stability of the bond between copper and the amide nitrogen of deprotonated Gly residues is confirmed in all cases. For the more interesting [Cu(HGGG)]2 complex, a dynamically entangled arrangement of the two domains with exchange of amide nitrogen bonds between the two copper centers emerges, which is consistent with the short Cu-Cu distance observed in experiments at full copper occupancy. PMID- 17333300 TI - Air-stable, heme-like water-soluble iron(II) porphyrin: in situ preparation and characterization. AB - Preparation of the water-soluble, kinetically labile, high-spin iron(II) tetrakis(4-sulfonatophenyl)porphyrin, Fe(II)TPPS(4-), has been realized in neutral or weakly acidic solutions containing acetate buffer. The buffer played a double role in these systems: it was used for both adjusting pH and, via formation of an acetato complex, trapping trace amounts of iron(III) ions, which would convert the iron(II) porphyrins to the corresponding iron(III) species. Fe(II)TPPS(4-) proved to be stable in these solutions even after saturation with air or oxygen. In the absence of acetate ions, however, iron(II) ions play a catalytic role in the formation of iron(III) porphyrins. While the kinetically inert iron(III) porphyrin, Fe(III)TPPS(3-), is a regular one with no emission and photoredox properties, the corresponding iron(II) porphyrin displays photoinduced features which are typical of sitting-atop complexes (redshifted Soret absorption and blueshifted emission and Q absorption bands, photoinduced porphyrin ligand-to metal charge transfer, LMCT, reaction). In the photolysis of Fe(II)TPPS(4-) the LMCT process is followed by detachment of the reduced metal center and an irreversible ring-opening of the porphyrin ligand, resulting in the degradation of the complex. Possible oxygen-binding ability of Fe(II)TPPS(4-) (as a heme model) has been studied as well. Density functional theory calculations revealed that in solutions with high acetate concentration there is very little chance for iron(II) porpyrin to bind and release O(2), deviating from heme in a hydrophobic microenvironment in hemoglobin. In the presence of an iron(III)-trapping additive that is much less strongly coordinated to the iron(II) center than the acetate ion, Fe(II)TPPS(4-) may function as a heme model. PMID- 17333301 TI - A new bisphosphonate-containing (99m)Tc(I) tricarbonyl complex potentially useful as bone-seeking agent: synthesis and biological evaluation. AB - Aiming to develop new bone-seeking radiotracers based on the organometallic core fac-[(99m)Tc(CO)(3)](+) with improved radiochemical and biological properties, we have prepared new conjugates with phosphonate pendant groups. The conjugates comprise a chelating unit for metal coordination, which corresponds to a pyrazolyl-containing backbone (pz) with a N,N,N donor-atom set, and a pendant diethyl phosphonate (pz-MPOEt), phosphonic acid (pz-MPOH) or a bisphosphonic acid (pz-BPOH) group for bone targeting. Reactions of the conjugates with the precursor [(99m)Tc(H(2)O)(3)(CO)(3)](+) yielded (mote than 95%) the single and well-defined radioactive species [(99m)Tc(CO)(3)(kappa(3)-pz-MPOEt)](+) (1a), [(99m)Tc(CO)(3)(kappa(3)-pz-MPOH](+) (2a) and [(99m)Tc(CO)(3)(kappa(3)-pz BPOH)](+) (3a), which were characterized by reversed-phase high-performance liquid chromatography . The corresponding Re surrogates (1-3), characterized by the usual analytical techniques, including X-ray diffraction analysis in the case of 1, allowed for macroscopic identification of the radioactive conjugates. These radioactive complexes revealed high stability both in vitro (phosphate-buffered saline solution and human plasma) and in vivo, without any measurable decomposition. Biodistribution studies of the complexes in mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion, occurring primarily through the renal-urinary pathway in the case of complex 3a. Despite presenting moderate bone uptake (3.04 +/- 0.47% injected dose per gram of organ, 4 h after injection), the high stability presented by 3a and its adequate in vivo pharmacokinetics encourages the search for new ligands with the same chelating unit and different bisphosphonic acid pendant arms. PMID- 17333302 TI - Characterization of the catalytically active Mn(II)-loaded argE-encoded N-acetyl L-ornithine deacetylase from Escherichia coli. AB - The catalytically competent Mn(II)-loaded form of the argE-encoded N-acetyl-L ornithine deacetylase from Escherichia coli (ArgE) was characterized by kinetic, thermodynamic, and spectroscopic methods. Maximum N-acetyl-L-ornithine (NAO) hydrolytic activity was observed in the presence of one Mn(II) ion with k(cat) and K(m) values of 550 s(-1) and 0.8 mM, respectively, providing a catalytic efficiency (k(cat)/K(m)) of 6.9 x 10(5) M(-1) s(-1). The ArgE dissociation constant (K(d)) for Mn(II) was determined to be 0.18 microM, correlating well with a value obtained by isothermal titration calorimetry of 0.30 microM for the first metal binding event and 5.3 microM for the second. An Arrhenius plot of the NAO hydrolysis for Mn(II)-loaded ArgE was linear from 15 to 55 degrees C, suggesting the rate-limiting step does not change as a function of temperature over this range. The activation energy, determined from the slope of this plot, was 50.3 kJ mol(-1). Other thermodynamic parameters were DeltaG(double dagger) = 58.1 kJ mol(-1), DeltaH(double dagger) = 47.7 kJ mol(-1), and DeltaS(double dagger) = -34.5 J mol(-1) K(-1). Similarly, plots of lnK(m) versus 1/T were linear, suggesting substrate binding is controlled by a single step. The natural product, [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]leucine (bestatin), was found to be a competitive inhibitor of ArgE with a K (i) value of 67 muM. Electron paramagnetic resonance (EPR) data recorded for both [Mn(II)_(ArgE)] and [Mn(II)Mn(II)(ArgE)] indicate that the two Mn(II) ions form a dinuclear site. Moreover, the EPR spectrum of [Mn(II)Mn(II)(ArgE)] in the presence of bestatin indicates that bestatin binds to ArgE but does not form a micro-alkoxide bridge between the two metal ions. PMID- 17333303 TI - Community water fluoridation and caries prevention: a critical review. AB - The aim of this paper was to critically review the current role of community water fluoridation in preventing dental caries. Original articles and reviews published in English language from January 2001 to June 2006 were selected through MEDLINE database. Other sources were taken from the references of the selected papers. For the past 50 years community water fluoridation has been considered the milestone of caries prevention and as one of the major public health measures of the 20th century. However, it is now accepted that the primary cariostatic action of fluoride occurs after tooth eruption. Moreover, the caries reduction directly attributable to water fluoridation have declined in the last decades as the use of topical fluoride had become more widespread, whereas enamel fluorosis has been reported as an emerging problem in fluoridated areas. Several studies conducted in fluoridated and nonfluoridated communities suggested that this method of delivering fluoride may be unnecessary for caries prevention, particularly in the industrialized countries where the caries level has became low. Although water fluoridation may still be a relevant public health measure in poor and disadvantaged populations, the use of topical fluoride offers an optimal opportunity to prevent caries among people living in both industrialized and developing countries. PMID- 17333305 TI - Adherence of Candida albicans to denture base acrylics and silicone-based resilient liner materials with different surface finishes. AB - This study evaluated the surface roughness and Candida albicans adherence on denture base acrylic resins and silicone-based resilient liners with different surface finishes. Four commercial denture base acrylic resins (three heat polymerized and one room temperature polymerized) and five silicone-based liner materials (two heat polymerized and three room temperature polymerized) (10 x 10 x 2 mm) were tested in this study. The materials were processed against glass or plaster or finished with a tungsten carbide bur. Surface roughness measurements were made using a profilometer with an optical scanner probe. All specimens were ultrasonically cleaned in water for 15 s, autoclave sterilized, and contaminated with C. albicans solution for adherence assay evaluation. The materials processed against the glass surface showed significantly lower surface roughness values (0.11 +/- 0.1-1.66 +/- 1.1 microm) than those of the materials processed against the dental plaster (2.61 +/- 0.2-6.12 +/- 2.8 microm) or roughening with a bur (1.48 +/- 0.2-7.05 +/- 1.2 microm; p < 0.05, one- or two-way analysis of variance). Also, the materials processed against the glass surface showed lower C. albicans adhesion (mean ranks 120.36) than those of the materials processed against the dental plaster (mean ranks 139.77) or roughening with a bur (mean ranks 143.06), but the differences were not statistically significant (p > 0.05, Kruskal-Wallis and Mann-Whitney). In all types of surface finishes, C. albicans adhesion on denture base acrylics was significantly less (mean ranks 90.18-90.40) than those of silicone liners (mean ranks 119.38-205.18; p < 0.01, Kruskal Wallis). PMID- 17333304 TI - Efficacy and oral side effects of two highly concentrated tray-based bleaching systems. AB - The aim of this study was to investigate the tooth-whitening efficacy and oral side effects of the two tray-based bleaching systems Visalys whitening (VW) and Opalescence PF (OP). A stratified, randomised distribution of the subjects (n = 60) to two treatment groups was performed according to baseline tooth brightness (L* values) as determined by colourimeter and to the criteria smoker/non-smoker. Tooth colour was evaluated by measuring L*a*b* values generated from standardised digital image analysis with Adobe Photoshop of the facial surfaces of the right central maxillary incisor. Tooth hypersensitivity, with intensity graded from 0 (no hypersensitivity) to 10 (high hypersensitivity), was assessed chair-side using an air syringe. After bleaching therapy, both treatment groups demonstrated significant improvements in tooth colour (p < or = 0.05). A shift towards less yellow (-Deltab*) and brighter (+DeltaL*) tooth colour was observed. Deltab* was significantly higher in the OP group in comparison to the VW group, DeltaL* showed no significant difference between the both treatment groups (p < or = 0.05). After bleaching, the intensity of tooth hypersensitivity was increased significantly compared to baseline in both groups (p < or = 0.05), with no significant difference between the both groups. Both highly concentrated bleaching systems are effective as tooth-whitening systems, with few reported side effects such as transient tooth hypersensitivity. PMID- 17333306 TI - Insights into catalytic activity of industrial enzyme Co-nitrile hydratase. Docking studies of nitriles and amides. AB - Nitrile hydratase (NHase) is an enzyme containing non-corrin Co3+ in the non standard active site. NHases from Pseudonocardia thermophila JCM 3095 catalyse hydration of nitriles to corresponding amides. The efficiency of the enzyme is 100 times higher for aliphatic nitriles then aromatic ones. In order to understand better this selectivity dockings of a series of aliphatic and aromatic nitriles and related amides into a model protein based on an X-ray structure were performed. Substantial differences in binding modes were observed, showing better conformational freedom of aliphatic compounds. Distinct interactions with postranslationally modified cysteines present in the active site of the enzyme were observed. Modeling shows that water molecule activated by a metal ion may easily directly attack the docked acrylonitrile to transform this molecule into acryloamide. Thus docking studies provide support for one of the reaction mechanisms discussed in the literature. PMID- 17333307 TI - Long-time molecular dynamics simulations of botulinum biotoxin type-A at different pH values and temperatures. AB - Botulinum neurotoxins type A (BoNT/A) are highly potent toxins, but are also useful in the treatment of illnesses. We studied the properties of BoNT/A at various temperatures and pH values in order to understand its toxicity and structure variations. The pH values of the environment of BoNT/A are obtained by changing the protonation states of certain titratable residue groups. Our results show that certain parts of the protein are active at acidic pH environments or at high temperatures. The protein is more stable in neutral environments at normal human body temperature, whereas, at high temperature, the protein is more stable in acidic environments. Also, the three domains of the protein tend to have relative motion rather than within individual domains. PMID- 17333309 TI - Adsorption and phase transitions in adsorbed systems: structural properties of CCl4 layers adsorbed on a graphite surface. AB - We present the results of simulations of a CCl(4) monolayer adsorbed on a graphite surface. The CCl(4) molecule was represented either by a shapeless superatom or by its atomic sites. The simulations were carried out over a large range of temperatures, from 20 K up to 340 K. We address the following problems: (1) the influence of molecular shape on the structure and stability of phases (particularly at low temperatures), and (2) the influence of the graphite corrugation on layer stability and mechanism of phase transitions. In particular, we discuss the possibility and conditions of the appearance of hexatic phase in the system. PMID- 17333308 TI - Comparative QSAR studies on peptide deformylase inhibitors. AB - Comparative quantitative structure-activity relationship (QSAR) analyses of peptide deformylase (PDF) inhibitors were performed with a series of previously published (British Biotech Pharmaceuticals, Oxford, UK) reverse hydroxamate derivatives having antibacterial activity against Escherichia coli PDF, using 2D and 3D QSAR methods, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR). Statistically reliable models with good predictive power were generated from all three methods (CoMFA r (2) = 0.957, q (2) = 0.569; CoMSIA r (2) = 0.924, q (2) = 0.520; HQSAR r (2) = 0.860, q (2) = 0.578). The predictive capability of these models was validated by a set of compounds that were not included in the training set. The models based on CoMFA and CoMSIA gave satisfactory predictive r (2) values of 0.687 and 0.505, respectively. The model derived from the HQSAR method showed a low predictability of 0.178 for the test set. In this study, 3D prediction models showed better predictive power than 2D models for the test set. This might be because 3D information is more important in the case of datasets containing compounds with similar skeletons. Superimposition of CoMFA contour maps in the active site of the PDF crystal structure showed a meaningful correlation between receptor-ligand binding and biological activity. The final QSAR models, along with information gathered from 3D contour and 2D contribution maps, could be useful for the design of novel active inhibitors of PDF. PMID- 17333310 TI - Molecular pharmacology of insect ion channels and implications for insect toxicology. PMID- 17333311 TI - Drinking and condom use: results from an event-based daily diary. AB - Although it is often assumed that drinking alcohol interferes with condom use, most studies on this topic do not meet the conditions required for causal interpretation. We examined the association of drinking to condom use using data from diaries of alcohol use and sexual encounters, collected over 8 weeks from college students and clients of a sexually transmitted disease clinic. This method establishes the temporal relationships between drinking and condom use and controls for individual differences by using a within-subjects analysis. Multilevel models that predicted condom use from alcohol use before the sexual encounter, partner type, and the use of other contraception showed that drinking before sex was unrelated to condom use. These results do not support the persistent notion that alcohol causes people to engage in sexual risk that they would avoid when sober; instead, people tend to follow their usual pattern of condom use, regardless of alcohol use. PMID- 17333313 TI - Effects of music on the recovery of autonomic and electrocortical activity after stress induced by aversive visual stimuli. AB - The purpose of this study was to compare the effects of music and white noise on the recovery of physiological measures after stressful visual stimulation. Twenty nine participants took part in the experiment. Visual stimulation with slides eliciting disgust was followed by subjectively pleasant music, sad music, and white noise in three consecutive sessions. The spectral power of the frontal and temporal EEG, skin conductance, heart rate, heart period variability, facial capillary blood flow, and respiration rate were recorded and analyzed. Aversive visual stimulation evoked heart rate deceleration, increased high frequency component of heart period variability, increased skin conductance level and skin conductance response frequency, decreased facial blood flow and velocity, decreased temporal slow alpha and increased frontal fast beta power in all three sessions. Both subjectively pleasant and sad music led to the restoration of baseline levels on most parameters; while white noise did not enhance the recovery process. The effects of pleasant music on post-stress recovery, when compared to white noise, were significantly different on heart rate, respiration rate, and peripheral blood flow. Both positive and negative music exerted positive modulatory effects on cardiovascular and respiratory activity, namely increased heart rate, balanced heart period variability, increased vascular blood flow and respiration rate during the post-stress recovery. Data only partially supported the "undoing" hypothesis, which states that positive emotions may facilitate the process of physiological recovery following negative emotions. PMID- 17333312 TI - The utility of non-proportional quota sampling for recruiting at-risk women for microbicide research. AB - In the context of a measurement development study designed to contextualize microbicide acceptability, a sample that represented a range of at-risk women and maintained the statistical power needed for validity analyses was required. A non proportional quota sampling strategy focused on race/ethnicity and number of sexual partners was utilized. This strategy resulted in enrollment of approximately equal proportions of Latina (31%), Black (36%), and White (32%) women, and an approximately 1:2 ratio of single-partnered (29%) and multi partnered (71%) women. About 17% of women screened were ineligible based on eligibility criteria; an additional 16% were ineligible based on quota closures. Most participants were recruited through word of mouth (39%), community-based organizations (19%), or media sources (19%). Women recruited through word of mouth had the highest screen-to-interview completion percentage (67%). Non proportional quota sampling is a feasible option for ensuring adequate representation of sample characteristics in microbicide research, but this goal should be weighed against cost and staff burden. PMID- 17333314 TI - A quantitative electroencephalographic correlate of sustained attention processing. AB - The objective of the present investigation was to develop a quantitative electroencephalographic measure (qEEG) that is sensitive and specific to changes in sustained human performance. A principal components analysis (PCA) was performed on the qEEG obtained from participants during a continuous performance test. Measures of sensitivity (proportion of correctly identified correct responses, or hits) and specificity (proportion of correctly identified incorrect responses, or misses) were calculated to assess the classification accuracy of each newly derived component. PCA solutions produced a right hemisphere component comprised of beta-wave activity measured from four unipolar sites (F8, C6a, C6, and T4) that appeared to be sensitive and specific to changes in human performance. Results provide evidence for the validity of a right hemisphere qEEG measure that is sensitive and specific to changes in sustained human performance. Consistent with the findings of previous research, the present findings implicate the right cerebral hemisphere in the sustained attention process. PMID- 17333315 TI - Preliminary results of an open label study of heart rate variability biofeedback for the treatment of major depression. AB - Major depressive disorder (MDD) is a common mood disorder that can result in significant discomfort as well as interpersonal and functional disability. A growing body of research indicates that autonomic function is altered in depression, as evidenced by impaired baroreflex sensitivity, changes in heart rate, and reduced heart rate variability (HRV). Decreased vagal activity and increased sympathetic arousal have been proposed as major contributors to the increased risk of cardiovascular mortality in participants with MDD, and baroreflex gain is decreased. STUDY OBJECTIVES: To assess the feasibility of using HRV biofeedback to treat major depression. DESIGN: This was an open-label study in which all eleven participants received the treatment condition. Participants attended 10 weekly sessions. Questionnaires and physiological data were collected in an orientation (baseline) session and Treatment Sessions 1, 4, 7 and 10. MEASUREMENTS AND RESULTS: Significant improvements were noted in the Hamilton Depression Scale (HAM-D) and the Beck Depression Inventory (BDI-II) by Session 4, with concurrent increases in SDNN, standard deviation of normal cardiac interbeat intervals) an electrocardiographic estimate of overall measure of adaptability. SDNN decreased to baseline levels at the end of treatment and at follow-up, but clinically and statistically significant improvement in depression persisted. Main effects for task and session occurred for low frequency range (LF) and SDNN. Increases in these variables also occurred during breathing at one's resonant frequency, which targets baroreflex function and vagus nerve activity, showing that subjects performed the task correctly. CONCLUSIONS: HRV biofeedback appears to be a useful adjunctive treatment for the treatment of MDD, associated with large acute increases in HRV and some chronic increases, suggesting increased cardiovagal activity. It is possible that regular exercise of homeostatic reflexes helps depression even when changes in baseline HRV are smaller. A randomized controlled trial is warranted. PMID- 17333316 TI - Grifolin induces apoptosis via inhibition of PI3K/AKT signalling pathway in human osteosarcoma cells. AB - Grifolin, a natural biologically active substance isolated from the edible bodies of the mushroom Albatrellus confluens, has been shown to inhibit proliferation and induce apoptosis in several cancer cell lines. But the mechanisms remain poorly understood. In this study, we investigated the apoptosis-inducing effects and the mechanisms of grifolin on human osteosarcoma cells. Our results demonstrated that grifolin induced concentration- and time-dependent suppression of proliferation and induction of apoptosis in U2OS and MG63 osteosarcoma cell lines. Grifolin induced the release of cytochrome c accompanied by activation of caspase-9, caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, z-VAD-fmk, a universal inhibitor of caspases, prevented caspase-3 activation and PARP cleavage and inhibted grifolin-induced cell growth inhibition. Furthermore, grifolin treatment resulted in a reduction in level of phosphorylated AKT, FOXO transcription factor, and glycogen synthase kinase 3 (GSK3). Knockdown of GSK3 with siRNA inhibited the apoptotic effects of grifolin. On the other hand, grifolin treatment down-regulated the expression of the inhibitor of apoptosis protein(IAP) in both osteosarcoma cells. Taken together, our results suggested that grifolin is able to suppress the phosphorylation of Akt and its substrates FOXO transcription factor and GSK3 in osteosarcoma cells causing the suppression of proliferation and induction of mitochondria- and caspase-dependent apoptosis. PMID- 17333317 TI - hCG treatment raises H2O2 levels and induces germ cell apoptosis in rat testis. AB - The clinical significance of exogenous hCG treatment is to stimulate steroidogenesis and spermatogenesis in the testis. However, the pathogenesis of detrimental effects on the testis arising out of chronic hCG treatment is yet to be clearly ascertained. In the present study we have shown that hCG treatment (100 IU/day) to rats for 30 days raises testicular oxidative stress leading to germ cell apoptosis and impairment of spermatogenesis. The treatment raises testicular H(2)O(2) levels along with increase in lipid peroxidation and concomitant decrease in the enzymatic antioxidant activities like superoxide dismutase, catalase and glutathione-s-transferase. The rise in the number of apoptotic germ cells was associated with up regulation of Fas protein expression and caspase-3 activity in the testis. However, serum testosterone which was elevated by 15 days of hCG treatment declined to pretreatment levels by 30 days. No significant alteration in serum gonadotropins was observed. The above findings indicate that the pathogenesis of deleterious effects following chronic hCG treatment is due to increase in testicular oxidative stress with high H(2)O(2) availability leading to apoptosis among germ cells. PMID- 17333318 TI - Role of iNOS-derived reactive nitrogen species and resultant nitrative stress in leukocytes-induced cardiomyocyte apoptosis after myocardial ischemia/reperfusion. AB - Polymorphonuclear leukocyte (PMN) accumulation/activation has been implicated as a primary mechanism underlying MI/R injury. Recent studies have demonstrated that PMNs express inducible nitric oxide synthase (iNOS) and produce toxic reactive nitrogen species (RNS). However, the role of iNOS-derived reactive nitrogen species and resultant nitrative stress in PMN-induced cardiomyocyte apoptosis after MI/R remains unclear. Male adult rats were subjected to 30 min of myocardial ischemia followed by 5 h of reperfusion. Animals were randomized to receive one of the following treatments: MI/R+vehicle; MI/R+L-arginine; PMN depletion followed by MI/R+vehicle; PMN depletion followed by MI/R+L-arginine; MI/R+1400 W; MI/R+1400 W+L-arginine and MI/R+ FeTMPyP. Ischemia/reperfusion induced and L-arginine-enhanced nitrative stress and cardiomyocyte apoptosis were determined. PMN depletion virtually abolished ischemia/reperfusion- induced PMN accumulation, attenuated ischemic/reperfusion-induced and L-arginine-enhanced nitrative stress, and reduced ischemic/reperfusion-induced and L-arginine enhanced cardiomyocyte apoptosis (P values all <0.01). Pre-treatment with 1400 W, a highly selective iNOS inhibitor, had no effect on PMN accumulation in the ischemic/reperfused tissue. However, this treatment reduced ischemia/reperfusion induced and L-arginine-enhanced nitrative stress and cardiomyocyte apoptosis to an extent that is comparable as that seen in PMN depletion group. Treatment with FeTMPyP, a peroxynitrite decomposition catalyst, had no effect on either PMN accumulation or total NO production. However, treatment with this ONOO(-) decomposition catalyst also reduced ischemia/reperfusion-induced and L-arginine enhanced nitrative stress and cardiomyocyte apoptosis (P values all <0.01). These results demonstrated that ischemic/reperfusion stimulated PMN accumulation may result in cardiomyocyte injury by an iNOS-derived nitric oxide initiated and peroxynitrite-mediated mechanism. Therapeutic interventions that block PMN accumulation, inhibit iNOS activity or scavenge peroxynitrite may reduce nitrative stress and attenuate tissue injury. PMID- 17333319 TI - Hypertonicity induced apoptosis in HL-60 cells in the presence of intracellular potassium. AB - Cell shrinkage is a hallmark of apoptosis. Potassium efflux, which is involved in cell shrinkage, has been previously described as an essential event of apoptosis. This study was designed to address the importance of potassium efflux in hypertonicity (450 mOsm and 600 mOsm) induced apoptosis. We initiated apoptosis in HL-60 cells in hypertonic medium consisting of either high concentrations of NaCl, mannitol or KCl. Apoptotic activity was evaluated based on the DNA content of the cells, annexin-V staining and calcium content. Apoptosis was initiated in hypertonic conditions consisting of high intracellular K(+). We demonstrate that apoptosis can occur in the presence of high intracellular potassium contrary to previous predictions. PMID- 17333320 TI - Overexpression of the cis/trans isomerase PTPA triggers caspase 3-dependent apoptosis. AB - PTPA, which possesses a peptidyl prolyl isomerase activity, was initially isolated as a protein that stimulates the weak phosphotyrosyl phosphatase activity of the Ser/Thr phosphatase PP2A. Here we show that transient overexpression of PTPA leads to cell death in a time-dependent manner in mammalian cells. PTPA-overproducing cells manifest hallmarks of apoptosis including chromatin condensation, membrane blebbing, positive staining with annexin V, dephosphorylation of Bad, and caspase-3 cleavage. Incubation of cells with the PP2A inhibitor okadaic acid does not prevent either dephosphorylation of Bad or PTPA-induced apoptosis, indicating that PTPA is unlikely to mediate its proapoptotic effect via PP2A. Moreover, we find no evidence for the involvement of either p53 or MAP kinases. Our data reveal a potential novel role for PTPA in the apoptotic process. PMID- 17333321 TI - When a "poach" is not a poach: re-defining human mate poaching and re-estimating its frequency. AB - For a romantic attraction to be considered a mate poach, the pursuer must be aware that, while attempting to attract the targeted individual, the target is already in a nominally exclusive relationship. We investigated a methodological alternative for investigating the frequency of mate poaching. We presented university students with a survey informed by a definition of poaching that, in contrast to that which informed previous surveys, explicitly stated that the poacher must be aware while pursuing the targeted individual that the target was already in an exclusive relationship. Relative to participants in previous research, the current participants reported fewer experiences with poaching. We concluded that the current survey reduced the likelihood of participants reporting experiences with non-poaching forms of romantic attraction as experiences with poaching, and thereby provided more accurate estimates of the frequency of poaching. We also investigated the frequency of a previously uninvestigated form and temporal context of poaching and used a more fine-grained measure of the frequency of poaching than used in previous research. Discussion addresses limitations of the current research and suggests future directions for addressing them. PMID- 17333322 TI - Older-sibling and younger-sibling sex ratios in Frisch and Hviid's (2006) national cohort study of two million Danes. AB - Frisch and Hviid (2006) recently reported a study of variables that predicted heterosexual and homosexual marriage in a national cohort of Danish men and women. They found no evidence that older brothers increase the probability that a man will legally marry another man. They concluded that their data raise questions about the universality of the widely confirmed finding that older brothers increase the probability that a man will be sexually oriented towards other men (the fraternal birth order effect). In the present article, Frisch and Hviid's data were reanalyzed using one of the procedures that have been used in prior studies of fraternal birth order. The results showed that the sex ratio of older brothers to older sisters was significantly higher than the expected value of 106 in all four of their study groups (heterosexually married men, homosexually married men, heterosexually married women, and homosexually married women). In contrast, the sex ratio of younger brothers to younger sisters approximated 106 in all four groups. According to this analysis, the only group whose data resembled data from previous studies was the homosexually married males. The writer concluded that one cannot interpret findings about the correlates of heterosexual and homosexual marriage as if they were findings about the correlates of heterosexual and homosexual orientation, and that this is underscored by comparing the markedly different older-sibling sex ratios obtained from heterosexually married persons (in the Danish study) and those obtained from heterosexually oriented persons (in previous studies). It is unclear what implications, if any, Frisch and Hviid's findings have for the study of sexual orientation in general. PMID- 17333323 TI - Latitude, digit ratios, and Allen's and Bergmann's rules: a comment on Loehlin, McFadden, Medland, and Martin (2006). PMID- 17333324 TI - Predictors of sexual coercion against women and men: a multilevel, multinational study of university students. AB - Several explanations have been forwarded to account for sexual coercion in romantic relationships. Feminist theory states that sexual coercion is the result of male dominance over women and the need to maintain that dominance; however, studies showing that women sexually coerce men point towards weaknesses in that theory. Some researchers have, therefore, suggested that it is the extent to which people view the other gender as hostile that influences these rates. Furthermore, much research suggests that a history of childhood sexual abuse is a strong risk factor for later sexual victimization in relationships. Few researchers have empirically evaluated the first two explanations and little is known about whether sexual revictimization operates for men or across cultures. In this study, hierarchical linear modeling was used to investigate whether the status of women and adversarial sexual beliefs predicted differences in sexual coercion across 38 sites from around the world, and whether sexual revictimization operated across genders and cultures. Participants included 7,667 university students from 38 sites. Results showed that the relative status of women at each site predicted significant differences in levels of sexual victimization for men, in that the greater the status of women, the higher the level of forced sex against men. In addition, differences in adversarial sexual beliefs across sites significantly predicted both forced and verbal sexual coercion for both genders, such that greater levels of hostility towards women at a site predicted higher levels of forced and verbal coercion against women and greater levels of hostility towards men at a site predicted higher levels of forced and verbal coercion against men. Finally, sexual revictimization occurred for both genders and across all sites, suggesting that sexual revictimization is a cross-gender, cross-cultural phenomenon. Results are discussed in terms of their contributions to the literature, limitations of the current study, and suggestions for future research. PMID- 17333325 TI - The effects of false positive and false negative physiological feedback on sexual arousal: a comparison of women with or without sexual arousal disorder. AB - The effects of false positive and false negative physiological feedback (vaginal photoplethymograph response print-out) on women's sexual arousal were examined. Participants included women without sexual dysfunction (n=16) and women with Sexual Arousal Disorder (SAD; n=15). Measures of subjective sexual arousal, physiological sexual arousal (vaginal pulse amplitude), expectancies, affect, and anxiety were obtained in response to viewing an erotic film. Results indicated that false positive feedback significantly increased subjective levels of sexual arousal, whereas false negative feedback significantly decreased subjective levels of sexual arousal in both groups. Sexually functional women had overall higher expectancies for sexual arousal than women with SAD. Unexpectedly, false positive feedback did not significantly impact physiological sexual arousal in sexually functional women; however, it resulted in significantly decreased responses in physiological sexual arousal in women with SAD. False negative feedback had no significant effect on physiological sexual response in sexually functional women or women with SAD. PMID- 17333326 TI - Implicit and explicit measurements of sexual preference in gay and heterosexual men: a comparison of priming techniques and the implicit association task. AB - The present study examined how well implicit measures were able to predict sexual orientation. Most previous research in the sexual orientation domain has been dependent upon self-report, which requires explicit, conscious awareness of sexual orientation and/or erotic preferences. On the other hand, implicit measurements are thought to be able to reflect immediate automatic reactions that may not be available to introspection. A total of 50 heterosexual and 25 homosexual men completed two implicit measures: the Implicit Association Task (IAT) and the Priming Task (PT). Sexual orientation was determined by self report. In the PT, participants classified words as either sexually attractive or unattractive. Each word was preceded by a "prime" that was a picture of either a male or a female. The IAT consisted of classifying these same words as sexually attractive or unattractive, and classifying the pictures as either male or female. Both the IAT and the PT had very good ability to predict sexual orientation with Area Under the Curves (AUC) of 0.97 and 0.86, respectively. Unlike many other reports of implicit measures of behavior, the IAT and the PT correlated strongly with each other, and also with the explicit measurements of sexual orientation. It was concluded that these implicit measures can provide a valuable tool for research into sexual orientation and erotic preference that can complement existing measures, such as self-report questionnaires and physiological changes in sexual arousal in response to erotic stimuli. PMID- 17333327 TI - Latino men's sexual behavior with transgender persons. AB - Male-to-female transgender persons are thought to be "vectors" for HIV/STI transmission, yet little quantitative information exists about the risk behavior of their male sexual partners who may serve as a "bridge" for HIV transmission into the general population. As part of an online survey examining the sexual risk behavior of Latino men who have sex with men (N = 1,026), we identified 44 (4%) participants who reported having had sex with a transgender partner. Compared with a randomly selected sub-sample of 200 men who did not report sex with a transgender person, sexual partners of transgender persons were almost three times more likely to have had unprotected sexual intercourse in the last three months. In addition, men who had sex with transgender persons were more likely to be HIV-positive; married, separated, or divorced; identify as bisexual or straight; have sex with women; and live in rural or small town communities. Regression analysis revealed that community size, sexual compulsivity, and having had a transgender partner were independent predictors of unprotected sex. Among Latino men who have sex with men, men with a history of sex with a transgender person appear more likely to be sexually compulsive and at greater risk for HIV and other sexually transmitted infections. These men may, therefore, also serve as a "bridge" for HIV transmission to (as opposed to from) the transgender population. PMID- 17333328 TI - Sexual decision-making in HIV-positive men who have sex with men: how moral concerns and sexual motives guide intended condom use with steady and casual sex partners. AB - Determinants of intended condom use with steady and casual sex partners were examined among Dutch HIV-positive men who have sex with men (MSM) (N = 296). Given the proposition that safer sex behavior among HIV-positive people is a form of prosocial behavior, the present study extended the general framework of the Theory of Planned Behavior with Schwartz's norm-activation theory and tested the assumption that personal norms would mediate the effects of other psychosocial factors on intended condom use for anal sex. In addition, it was hypothesized that, depending on the context in which sex occurs, specific motives for unprotected anal sex may have a negative influence on intended condom use and, as such, undermine a prosocial tendency to practice safer sex. Therefore, we also investigated the influence of sexual motives for unprotected anal sex on intended condom use with steady and casual sex partners. Results indicated that the Theory of Planned Behavior adequately predicted condom use intentions (for casual sex partners and steady sex partners, the explained variance was 52% and 53%, respectively). However, our proposed model of sexual decision-making significantly improved the prediction of behavioral intentions. For steady and casual sex partners, the assumption of the mediating role of personal norms on condom use intention was confirmed empirically. Additionally, sexual motives for unprotected anal sex exerted, as expected, a direct, negative effect on condom use intention with casual sex partners. The implications of the findings for future research and the development of HIV-prevention programs for HIV-positive MSM are discussed. PMID- 17333329 TI - Prevalence of masturbation and associated factors in a British national probability survey. AB - A stratified probability sample survey of the British general population, aged 16 to 44 years, was conducted from 1999 to 2001 (N = 11,161) using face-to-face interviewing and computer-assisted self-interviewing. We used these data to estimate the population prevalence of masturbation, and to identify sociodemographic, sexual behavioral, and attitudinal factors associated with reporting this behavior. Seventy-three percent of men and 36.8% of women reported masturbating in the 4 weeks prior to interview (95% confidence interval 71.5% 74.4% and 35.4%-38.2%, respectively). A number of sociodemographic and behavioral factors were associated with reporting masturbation. Among both men and women, reporting masturbation increased with higher levels of education and social class and was more common among those reporting sexual function problems. For women, masturbation was more likely among those who reported more frequent vaginal sex in the last four weeks, a greater repertoire of sexual activity (such as reporting oral and anal sex), and more sexual partners in the last year. In contrast, the prevalence of masturbation was lower among men reporting more frequent vaginal sex. Both men and women reporting same-sex partner(s) were significantly more likely to report masturbation. Masturbation is a common sexual practice with significant variations in reporting between men and women. PMID- 17333330 TI - Mitochondrial CR-1 variation in Sardinian hares and its relationships with other Old World hares (Genus Lepus). AB - Among the European fauna, the Sardinian hare (Lepus sp.) is peculiar in that it differs from all other hares inhabiting the continent. Here, we report on the variation of a 461 bp sequence of hypervariable domain 1 of the mitochondrial control region, examined in 42 hares collected throughout Sardinia and compared to the corresponding sequences of different Lepus taxa. Seventeen novel haplotypes were found in the Sardinian population, resulting in a haplotype diversity of 0.840 and a nucleotide diversity of 0.012. As a result of Bayesian and principal coordinates analyses, Sardinian hares were grouped with North African hares, constituting a monophyletic clade that diverges from all other Old World hares, including Cape hares from South Africa and East Asia. Hence, our data agree that populations inhabiting North Africa and Sardinia form a distinct taxon, which could possibly be included in the L. capensis superspecies. Moreover, two corresponding lineages can be found in Sardinia and Tunisia, providing evidence of a common origin of the two populations and thus supporting the hypothesis that North African hares were introduced into the island in historical times. Our data show that the two lineages differ in their geographic distribution throughout the island and that the wild Sardinian population also shows the signature of a postintroduction demographic expansion. PMID- 17333331 TI - Partial characterization and evolution of Adh-Adhr in Drosophila dunni. AB - We sequenced 2123 bp of the Adh-Adhr genomic region of Drosophila dunni of the cardini group from two cloned DNA PCR fragments and from two cDNA clones of an Adh transcript. This comprises the Adh coding region and introns, 3' UTR, intergenic sequence, and most of Adhr, which is 260 bp downstream of Adh. Both genes have the typical Drosophila melanogaster Adh structure of three exons and two introns, except for changes in the putative 8 bp sequence involved in downregulation within the 3' UTR of Adh. Two amino acid substitutions could explain the low activity previously reported for this enzyme in D. dunni: Thr --> Lys at position 191 and Val --> Thr at position 189. D. dunni's Adh has the lowest codon bias reported so far for Drosophila species, and based on analysis of the nucleotide substitution rate, it is less conserved than Adhr. PMID- 17333332 TI - A randomized controlled trial of a decision aid for women considering genetic testing for breast and ovarian cancer risk. AB - PURPOSE: To measure the effectiveness of a tailored decision aid (DA) designed to help women make informed decisions about genetic testing for breast/ovarian cancer risk. METHODS: A total of 145 women were randomized to receive the DA or a control pamphlet at the end of their first genetic counseling consultation. Of these, 120 (82.8%) completed two questionnaires, 1 week and 6 months post consultation. RESULTS: While the DA had no effect on informed choice, post decisional regret or actual genetic testing decision, the trial showed that women who received the DA had higher knowledge levels and felt more informed about genetic testing than women who received the control pamphlet (chi(2)(2) = 6.82; P = 0.033; chi(2)(1) = 4.86; P = 0.028 respectively). The DA also helped women who did not have blood drawn at their first consultation to clarify their values with regards to genetic testing (chi(2)(1) = 5.27; P = 0.022). Women who received the DA were less likely to share the information with other family members than women in the control condition (chi(2)(1) = 8.78; P = 0.003). CONCLUSIONS: Decision aids are an effective decision-support strategy for women considering genetic testing for breast/ovarian cancer risk, and are most effective before the patient has made a decision, which is generally at the point of having blood drawn. PMID- 17333333 TI - BARD1 and breast cancer in Poland. AB - PURPOSE: To investigate whether or not a genetic variant in BARD1 (Cys557Ser) contributes to early-onset breast cancer in Poland, or modifies the risk of breast cancer in women with an inherited predisposition to breast cancer. EXPERIMENTAL DESIGN: We studied 3,188 unselected Polish women with breast cancer and 1,038 healthy controls. All women were genotyped for the BARD1 Cys557Ser variant and for known founder mutations in BRCA1 (three mutations), CHEK2 (four mutations), and NBS1 (one mutation). RESULTS: A BARD1 variant was seen in 150 of 3,188 breast cancer cases (4.7%) and in 40 of 1,038 controls (3.8%) (OR = 1.2; 95% CI = 0.9-1.7). The risk associated with the BARD1 variant was not significantly greater in women with familial cancer (OR = 1.5; 95% CI = 0.8-2.7), or with an inherited mutation in BRCA1 (OR = 0.9; 95% CI = 0.4-2.2), CHEK2 (OR = 1.0; 95% CI = 0.5-2.1), or NBS1 (OR = 1.3; 95% CI = 0.2-10.2). Modest associations were observed among the subgroups of women with very early onset breast cancer (OR = 2.9; 95% CI = 1.2-7.1) and with medullary breast cancer (OR = 1.8; 95% CI = 0.9-3.7). CONCLUSION: There was no clear association between the presence of the BARD1 Cys557Ser allele and breast cancer in Poland. Furthermore, the BARD1 Cys557Ser allele does not appear to modify the risk of breast cancers among carriers of BRCA1 mutations, or of other predisposing mutations. The allele may predispose to breast cancers of certain histologic subtypes, but further studies are needed to confirm these findings. PMID- 17333334 TI - Activation of protein kinase A (PKA) signaling mitigates the antiproliferative and antiinvasive effects of alpha-difluoromethylornithine in breast cancer cells. AB - We have shown that alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, the first and rate-limiting enzyme in polyamine synthesis, has significant antiproliferative and antiinvasive effects in breast cancer cells. We have also reported that these antitumor effects are associated with activation of multiple signaling pathways, including STAT-3, STAT-1, Jun-N Terminal kinase (JNK), and Mitogen activated protein kinase (MAPK), the latter being found to mediate its antiinvasive action in MDA-MB-435 cells. The present experiments were designed to test the effect of DFMO on the protein kinase A (PKA) pathway and determine its biological significance. We found that DFMO administration (1 mM) to MDA-MB-435 breast cancer cells significantly increased cAMP response element (CRE)-binding protein (CREB) phosphorylation as well as the transactivation of pCRE-luc, a CREB-dependent promoter activated by PKA. To determine the significance of this biochemical effect of DFMO, we used the PKA inhibitor H89 which, as expected, suppressed in a dose-dependent manner (1 and 10 microM) basal and DFMO-induced CREB phosphorylation in our system. Administration of H89 alone was able to suppress proliferation of MDA-MB-435 cells when used at a concentration (10 microM) shown to completely block basal CREB phosphorylation. At concentrations of 0.5 and 1 muM, H89 treatment, while having no antiproliferative effect of its own, potentiated in a dose-dependent fashion the growth inhibitory action of a suboptimal concentration of DFMO (0.01 mM). Ten micromoles of H89 reduced invasiveness of MDA-MB-435 cells in matrigel by approximately 40% (an effect similar to that of 1 mM DFMO). The combination treatment further reduced invasiveness by approximately 80% (P < 0.01 versus the individual treatments). H89 treatment (10 microM) partially reduced DFMO-induced phosphorylation of STAT-3 but not that of STAT-1, Extracellular regulated kinase (ERK), and JNK. In conclusion, our results indicate that PKA signaling exerts proproliferative and proinvasive effects in our experimental system. Therefore, its activation by DFMO represents a compensatory mechanism which should be blocked in order to maximize the antitumor action of the drug. Our data are also consistent with the notion that STAT-3 activation by DFMO is at least in part mediated through the PKA pathway. PMID- 17333335 TI - Farnesol, a mevalonate pathway intermediate, stimulates MCF-7 breast cancer cell growth through farnesoid-X-receptor-mediated estrogen receptor activation. AB - Farnesoid X receptor (FXR) is a metabolic nuclear receptor expressed in the liver and traditionally considered as a bile acid sensor. Yet, FXR has been recently demonstrated in other tissues and cells, such as the kidneys, the adrenals, and arterial smooth muscle cells. Immunohistochemical data reported in this study point to the expression of FXR in human breast cancer. In addition, FXR expression was also found by Western blotting and immunofluorescence microscopy in breast-cancer-derived cell lines MCF-7 (estrogen receptor [ER]-positive) and MDA-MB-231 (ER-negative). The FXR activator farnesol, a mevalonate pathway intermediate, exerts a mitogenic effect on MCF-7 cells. The growth stimulation is completely suppressed by antiestrogens. In contrast, MDA-MB-231 cells appear farnesol-insensitive, suggesting an involvement of ER in farnesol mitogenicity. In accordance with this interpretation, farnesol induces in MCF-7 cells a decrease of ER level, consistent with a phenomenon of receptor downregulation. Farnesol also increases progesterone receptor (PgR) expression in MCF-7 cells and stimulates ER-mediated gene transactivation in MVLN cells (MCF-7 cells stably transfected with an ER reporter gene). Of note, both effects of farnesol on ER expression and activity are completely suppressed by antiestrogens. In addition, farnesol-induced PgR is markedly reduced by FXR gene silencing (siRNA), demonstrating the involvement of FXR in the estrogenic effects of farnesol. Finally, coimmunoprecipitation experiments (FXR immunoprecipitation followed by Western blot analysis of ER in the immunoprecipitate) produced definite evidence that FXR interacts with ER. Altogether, these observations reveal the hitherto unreported presence of FXR in breast cancer and show that the latter receptor functionally interacts with ER. The occurrence of such a crosstalk calls for some caution regarding the pharmacological use of FXR agonists. PMID- 17333337 TI - Effects of polyamine depletion by alpha-difluoromethylornithine on in vitro and in vivo biological properties of 4T1 murine mammary cancer cells. AB - Increased polyamine synthesis has been associated with proliferation and progression of breast cancer, and thus, is a potential target for anticancer therapy. Polyamine depletion by alpha-difluoromethylornithine (DFMO) has been shown to decrease pulmonary and bone metastasis from human breast cancer cell xenografts. Following these observations, this study was designed to test the effects of DFMO on in vitro and in vivo features of the highly invasive and metastatic 4T1 murine mammary cancer cells. DFMO inhibited proliferation, caused G1-S arrest, and suppressed in vitro invasiveness of 4T1 cells. In contrast to our previous findings with MDA-MB-435 cells, DFMO did not affect the activation of signal transducers and activator of transcription 3, c-Jun N-terminal kinase, and extracellular signal-regulated kinase, but decreased phosphorylation of p38. DFMO did not alter the expression of Twist. DFMO delayed the orthotopic growth of 4T1 xenografts in association with suppressed putrescine and spermidine levels but increased levels of spermine. DFMO did not affect pulmonary metastasis when primary tumors of control and DFMO-treated mice were matched for size. Interestingly, DFMO reduced Ki-67 expression only in the primary tumors but did not affect its expression in the metastatic tumors in the lung. Cleaved caspase-3 expression was not affected by DFMO in either the primary tumors or the pulmonary metastasis. In summary, DFMO treatment markedly inhibited in vitro proliferation and invasiveness of 4T1 cells and retarded the growth of orthotopic xenografts in mice. The failure of DFMO to inhibit pulmonary metastasis in this system appears to be due, at least in part, to its lack of antiproliferative effect at the metastatic sites. PMID- 17333336 TI - Loss of expression of FANCD2 protein in sporadic and hereditary breast cancer. AB - Fanconi anemia (FA) is a recessive disorder associated with progressive pancytopenia, multiple developmental defects, and marked predisposition to malignancies. FA is genetically heterogeneous, comprising at least 12 complementation groups (A-M). Activation of one of the FA proteins (FANCD2) by mono-ubiquitination is an essential step in DNA damage response. As FANCD2 interacts with BRCA1, is expressed in proliferating normal breast cells, and FANCD2 knockout mice develop breast tumors, we investigated the expression of FANCD2 in sporadic and hereditary invasive breast cancer patients to evaluate its possible role in breast carcinogenesis. Two tissue microarrays of 129 and 220 sporadic breast cancers and a tissue microarray containing 25 BRCA1 germline mutation-related invasive breast cancers were stained for FANCD2. Expression results were compared with several clinicopathological variables and tested for prognostic value. Eighteen of 96 (19%) sporadic breast cancers and two of 21 (10%) BRCA1-related breast cancers were completely FANCD2-negative, which, however, still showed proliferation. In the remaining cases, the percentage of FANCD2-expressing cells correlated strongly with mitotic index and percentage of cells positive for the proliferation markers Ki-67 and Cyclin A. In immunofluorescence double staining, coexpression of FANCD2 and Ki-67 was apparent. In survival analysis, high FANCD2 expression appeared to be prognostically unfavorable for overall survival (p = 0.03), independent from other major prognosticators (p = 0.026). In conclusion, FANCD2 expression is absent in 10-20% of sporadic and BRCA1-related breast cancers, indicating that somatic inactivating (epi)genetic events in FANCD2 may be important in both sporadic and hereditary breast carcinogenesis. FANCD2 is of independent prognostic value in sporadic breast cancer. PMID- 17333338 TI - Screening for ATM sequence alterations in African-American women diagnosed with breast cancer. AB - BACKGROUND: Women who are heterozygous for variants in the ataxia telangiectasia mutated (ATM) gene, ATM carriers, have been reported to be at increased risk for breast cancer compared with women who do not posses an alteration in this gene. Aside from BRCA1 and BRCA2, there are few data on breast cancer susceptibility genes in African-American women. The goal of this study was to determine whether there is evidence that ATM is a breast cancer susceptibility gene in African American women. METHODS: One hundred thirty two African-American women were screened for ATM sequence alterations. Thirty-seven (28%) were women with a histological diagnosis of breast cancer (cases). These women were not selected on the basis of a breast cancer family history. Ninety-five (72%) were age-matched women who had not been diagnosed with breast cancer (controls). Genetic variants were identified using denaturing high performance liquid chromatography (DHPLC). RESULTS: Twenty-three of the 37 (62%) cases possessed at least one ATM variant. Fifty-eight of the 95 (61%) (P = 0.54) age-matched controls harbored at least one ATM variant. For subjects specifically possessing missense variants, 46% of cases and 48% of controls had these types of sequence variants. In addition, 19% of cases and 34% of controls possessed multiple ATM sequence variants (P = 0.07). The most common polymorphisms were the 378 T --> A which was seen in 19% of cases and 27% of controls (P = 0.22), 5557 G --> A identified in 22% of cases and 18% of controls (p = 0.40), 2685 A --> G which was detected in 11% of cases and 6% of controls (P = 0.22), and 1254 A --> G which was found in 3% of cases and 9% of controls (P = 0.36). Hence, there were no significant differences in any of the genetic variants detected between the case and control subjects. CONCLUSION: We found no statistically significant differences in the overall frequency of ATM variants, nor any specific variant type or group, between African-American women who had been diagnosed with breast cancer compared with an age-matched cohort of African-American women who did not have breast cancer. ATM, therefore, does not appear to represent a breast cancer susceptibility gene in the general African American population. PMID- 17333339 TI - Analysis of telomere damage by fluorescence in situ hybridisation on micronuclei in lymphocytes of breast carcinoma patients after radiotherapy. AB - Radiotherapy has become an indispensable tool in the effective management of most of the cancers. There have been efforts earlier to study the differential radio sensitivity patterns in patients undergoing radiation treatment to correlate with treatment induced complications such as tissue injury, cell death, and chromosomal aberration frequencies etc. The present study is an attempt to correlate the radiation-induced damage in the peripheral blood lymphocytes (PBLs) of breast cancer patients with the frequency of telomere mediated chromosomal damage. Blood samples from 55 patients with (Gr-II and Gr-III) CA-breast were obtained pre- and post-radiotherapy. The patients were treated with external beam radiotherapy of 50.4 Gy over a period of 6 weeks. Chromosome damage was measured by analysing micronucleus (MN) frequency in PBLs. The MN-frequency of the irradiated patients increased significantly compared to the patients being self controls. The micronuclei were hybridized with telomere probes to study the extent of telomere damage. The fluorescence signals of the telomere regions in the first generation of the binucleated cells were significantly higher in the post-radiotherapy patients. There was also significant correlation observed in the patients with higher-grade tumours. Inter-individual variability was observed in the radiation-induced MN frequency in lymphocytes of patients after six weeks of radiotherapy. There was a significant correlation between functionally intact telomeres and the cellular response to ionising radiation. Our findings suggest that fluorescence in situ hybridisation on micronuclei could be effectively used as routine clinical application to determine the individual sensitivity to ionising radiation with respect to telomere damage. PMID- 17333340 TI - Letrozole in advanced breast cancer: the PO25 trial. AB - Tamoxifen has been a standard first-line endocrine therapy for post-menopausal women with hormone-responsive advanced breast cancer, but more than half of patients fail to respond and time to progression is less than 12 months in responders. The third-generation aromatase inhibitors were developed to provide more effective alternatives to tamoxifen. In the Femara Study PO25, post menopausal women with advanced breast cancer were randomized to receive letrozole 2.5 mg (n=453) or tamoxifen 20 mg (n=454) given orally daily until progressive disease occurred. Patients were permitted to cross over to the other treatment at progression. In the primary efficacy analysis, median time to progression (TTP) was significantly longer with letrozole than with tamoxifen (9.4 months vs. 6.0 months, respectively; P<0.0001). The objective response rate (ORR) was significantly higher for letrozole than for tamoxifen (32% vs. 21%; P=0.0002). Prospectively planned analyses of the intent-to-treat population showed that letrozole significantly improved overall survival (OS) compared with tamoxifen over the first 24 months of the trial. An exploratory analysis of patients, who did not cross over, indicated a median OS benefit of 14 months for letrozole compared with tamoxifen. Letrozole is the only third-generation aromatase inhibitor that has demonstrated significant improvements in ORR, TTP, and early OS. PMID- 17333341 TI - Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. AB - Large numbers of hormone replacement therapies (HRTs) are available for the treatment of menopausal symptoms. It is still unclear whether some are more deleterious than others regarding breast cancer risk. The goal of this study was to assess and compare the association between different HRTs and breast cancer risk, using data from the French E3N cohort study. Invasive breast cancer cases were identified through biennial self-administered questionnaires completed from 1990 to 2002. During follow-up (mean duration 8.1 postmenopausal years), 2,354 cases of invasive breast cancer occurred among 80,377 postmenopausal women. Compared with HRT never-use, use of estrogen alone was associated with a significant 1.29-fold increased risk (95% confidence interval 1.02-1.65). The association of estrogen-progestagen combinations with breast cancer risk varied significantly according to the type of progestagen: the relative risk was 1.00 (0.83-1.22) for estrogen-progesterone, 1.16 (0.94-1.43) for estrogen dydrogesterone, and 1.69 (1.50-1.91) for estrogen combined with other progestagens. This latter category involves progestins with different physiologic activities (androgenic, nonandrogenic, antiandrogenic), but their associations with breast cancer risk did not differ significantly from one another. This study found no evidence of an association with risk according to the route of estrogen administration (oral or transdermal/percutaneous). These findings suggest that the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone or dydrogesterone. PMID- 17333342 TI - Prevalence of BRCA1 and BRCA2 genomic rearrangements in a cohort of consecutive Italian breast and/or ovarian cancer families. AB - Germline point mutations in BRCA1 and BRCA2 genes account for about 30% of the inherited breast and ovarian cancers. Germline genomic rearrangements have been found in both BRCA1 and BRCA2 genes, but the extent to which these alterations might contribute to increasing the actual mutation detection rate is still debated. Here we screened a cohort of 112 consecutive Italian families at moderate-to-high risk for breast and/or ovarian cancer for BRCA1 and BRCA2 point mutations and genomic rearrangements. Of the 83 point mutation negative probands, two (2.4%) showed BRCA1 rearrangements, accounting for 10.5% of the BRCA1 mutations. BRCA1 del18-19 has been previously described in another Italian family, while the molecular characterization of the BRCA1 del23-24 is given here for the first time. Conversely, we failed to identify any BRCA2 rearrangements even in the hereditary breast cancer families, where we detected an higher prevalence of BRCA2 compared to BRCA1 point mutations. Our results support the idea that search for BRCA1 rearrangements should be included in the genetic screening of even moderate risk breast/ovarian cancer families. In contrast, they suggest BRCA2 rearrangements might be very rare out of the high risk families including a male breast cancer. PMID- 17333343 TI - BRCA1 and BRCA2 status in a Central Sudanese series of breast cancer patients: interactions with genetic, ethnic and reproductive factors. AB - The etiology of breast cancer in Africa is scarcely investigated. Breast cancer was responsible for 456/2,233 cancer patients (20.4%) ascertained between 1999 and 2004 at Gezira University, Central Sudan. Male breast cancer accounted for 16/456 patients (3.5%), 275/440 female patients (62.5%) were premenopausal and 150/440 cases (34%) occurred in women with > or =5 childbirths. We characterized for germline BRCA1/2 mutations a one-year series of patients (34 females, 1 male) selected by diagnosis within age 40 years or male gender. Overall 33/35 patients were found to carry 60 BRCA1/2 variants, of which 17 (28%) were novel, 22 (37%) reported in populations from various geographic areas and 21 (35%) reported worldwide. Detected variants included 5 truncating mutations, one of which (in BRCA2) was in the male patient. The 55 non-truncating variants included 3 unclassified variants predicted to affect protein product and not co-occurring with a truncating mutation in the same gene. Patients were from different tribes but AMOVA showed that most BRCA1/2 variation was within individuals (86.41%) and patients clustered independently of tribe in a phylogenetic tree. Cluster analysis based on age at cancer diagnosis and reproductive variables split female patients in two clusters that, by factor analysis, were explained by low versus high scores of the total period occupied by pregnancies and lactation. The cluster with low scores comprised all 4 patients with truncating mutations and 3 of the 4 carriers of unclassified variants predicted to affect protein product. Our findings suggest that in Central Sudan BRCA1/2 represent an important etiological factor of breast cancer in males and young women less exposed to pregnancy and lactation. Factors other than BRCA1/2 may contribute to breast cancer in young highly multiparous women who breast-fed for prolonged periods. PMID- 17333344 TI - Molecular basis of antifolate resistance. AB - Folates play a key role in one-carbon metabolism essential for the biosynthesis of purines, thymidylate and hence DNA replication. The antifolate methotrexate has been rationally-designed nearly 60 years ago to potently block the folate dependent enzyme dihydrofolate reductase (DHFR) thereby achieving temporary remissions in childhood acute leukemia. Recently, the novel antifolates raltitrexed and pemetrexed that target thymidylate synthase (TS) and glycineamide ribonucleotide transformylase (GARTF) were introduced for the treatment of colorectal cancer and malignant pleural mesothelioma. (Anti)folates are divalent anions which predominantly use the reduced folate carrier (RFC) for their cellular uptake. (Anti)folates are retained intracellularly via polyglutamylation catalyzed by folylpoly-gamma-glutamate synthetase (FPGS). As the intracellular concentration of antifolates is critical for their pharmacologic activity, polyglutamylation is a key determinant of antifolate cytotoxicity. However, anticancer drug resistance phenomena pose major obstacles towards curative cancer chemotherapy. Pre-clinical and clinical studies have identified a plethora of mechanisms of antifolate-resistance; these are frequently associated with qualitative and/or quantitative alterations in influx and/or efflux transporters of (anti)folates as well as in folate-dependent enzymes. These include inactivating mutations and/or down-regulation of the RFC and various alterations in the target enzymes DHFR, TS and FPGS. Furthermore, it has been recently shown that members of the ATP-binding cassette (ABC) superfamily including multidrug resistance proteins (MRP/ABCC) and breast cancer resistance protein (BCRP/ABCG2) are low affinity, high capacity ATP-driven (anti)folate efflux transporters. This transport activity is in addition to their established facility to extrude multiple cytotoxic agents. Hence, by actively extruding antifolates, overexpressed MRPs and/or BCRP confer antifolate resistance. Moreover, down regulation of MRPs and/or BCRP results in decreased folate efflux thereby leading to expansion of the intracellular folate pool and antifolate resistance. This chapter reviews and discusses the panoply of molecular modalities of antifolate resistance in pre-clinical tumor cell systems in vitro and in vivo as well as in cancer patients. Currently emerging novel strategies for the overcoming of antifolate-resistance are presented. Finally, experimental evidence is provided that the identification and characterization of the molecular mechanisms of antifolate-resistance may prove instrumental in the future development of rationally-based novel antifolates and strategies that could conceivably overcome drug-resistance phenomena. PMID- 17333345 TI - The folate receptor: what does it promise in tissue-targeted therapeutics? AB - For over a decade the folate receptor has been intensively investigated as a means for tumor-specific delivery of a broad range of experimental therapies including several conceptually new treatments. Despite a few set backs in clinical trials, the literature is replete with encouraging in vitro and pre clinical studies of gynecological and other tumors and more therapeutic approaches are ready for clinical testing. Recent studies have added myelogenous leukemias to the list of candidate cancers for FR-targeted therapies. Each approach faces unique challenges in translation that could be addressed through a mechanistic understanding of the function and expression of the receptor in the appropriate experimental systems and by improvements in the technology. This review discusses FR in the context of positive recent developments in broad areas of FR-targeted therapy and attempts to highlight its potential and the anticipated challenges. PMID- 17333346 TI - Cultural variations in mothers' attributions: influence of child attention deficit/hyperactivity disorder. AB - The attributions made by Chinese immigrant (n = 28) and Euro-Canadian (n = 27) mothers of 5- to 9-year-old boys regarding the causes of child prosocial and problem behaviors exhibited by children with and without attention deficit/hyperactivity disorder (ADHD) were investigated. Mothers' attributions were elicited using audio-taped scenarios of child behavior. In one-half of the scenarios, the child was described as having ADHD. All mothers attributed less responsibility to the child or to the parent for problem behaviors when the child was described as having ADHD than when the child was described as not having a behavior disorder. Mothers also attributed prosocial child behaviors and the behavior of children without ADHD more to parental factors. In comparison to Euro Canadian mothers, Chinese immigrant mothers saw children as less responsible for prosocial behavior. Mothers also completed a measure of beliefs about ADHD. Although there were some subtle cultural differences in these beliefs, mothers from both cultural groups endorsed generally accurate beliefs about ADHD. Implications for understanding the cultural uniqueness and similarities of maternal attitudes regarding child behavior and ADHD are discussed. PMID- 17333347 TI - Teenagers response to threat of war and terror: gender and the role of social systems. AB - This study focuses on the role of gender and the way social systems (family and friends' support, stress attributed to parents, friends and others in the community) are perceived in contributing to the reaction to stressors of war and threat of terror among teenagers living in Israel along the Lebanese border. The study was implemented shortly after Israel's withdrawal from Lebanon with a sample of 353 teenagers. The study is based on the teenagers' self-report. The results reveals the following: (a) gender relates significantly to level of stress but not to general life satisfaction; (b) stress attributed to the parents and to the peers has a greater contribution to the level of stress than the supportive family atmosphere and peer support; (c) stress attributed to the parents and peers was found to be a mediator between gender and level of stress; (d) supportive family atmosphere was found to be a mediator between gender and one measurement of stress, while peer support was not found to have any mediating role. Special attention is given to the finding that stress attributed to parents and friends has greater significance than the support provided by them. PMID- 17333348 TI - A community epidemiological survey of generalized anxiety disorder in Hong Kong. AB - Generalized anxiety disorder (GAD) is understudied in Asian communities. There were 3,304 Chinese subjects (aged 15-60 years) randomly drawn from the general population of Hong Kong and successfully interviewed. The participation rate was 65.8%. The six-month prevalence of DSM-IV GAD was 4.1%. Over half of the GAD subjects reported palpitations and bowel symptoms. Comorbid depressive mood (65%) and substance use (35%) were common. Forty-one percent of GAD subjects sought help, usually from general practitioners who prescribed tranquilizers after negative physical investigations. Telephone-based surveys have limitations but provide an affordable and destigmatizing alternative to face-to-face surveys for communities with limited mental health resources. PMID- 17333349 TI - Changing trends in endosonography: linear imaging and tissue are increasingly the issue. AB - The indications and uses of endoscopic ultrasound (EUS) are expanding. The role of EUS-guided fine needle aspiration (EUS-FNA) is considered an essential aspect of EUS practice. A significant change in the indications and technology used for EUS has occurred. This study was designed to compare the use of radial, linear, and miniprobe endosonography equipment during a 10-year period in a single, large, EUS practice. A retrospective review of an EUS experience at a single high volume center was performed. In this single-center experience, there has been an increase in the volume of EUS and EUS-FNA. For luminal cancer-staging cases, the radial echoendoscope is the predominant scope used for examination and has not changed significantly. In contrast, for pancreaticobiliary and mediastinal indications, the use of the linear array echoendoscope alone has increased and currently is the preferred scope for examination (33% vs. 76%, P < 0.001; 46% vs. 96%, P < 0.001). In these cases requiring EUS-FNA, the use of the linear array scope alone has increased from 17% to 73%. In this single-center experience, EUS has shifted from an imaging technology to an image-guided biopsy and therapeutic technology. The use of the linear array EUS alone has increased, especially in the evaluation of pancreatobiliary and mediastinal disease and when fine-needle aspiration is performed. PMID- 17333351 TI - Wilson's disease: what lies beneath. PMID- 17333350 TI - Hepatitis C virus infection--pathobiology and implications for new therapeutic options. AB - Despite progress in therapeutic approaches for the elimination of hepatitis C, chronic hepatitis C virus infection remains an important cause of liver disease. Therapeutic intervention with the currently available interferon-based treatment regimens is quite successful, but treatment is difficult to tolerate and is contraindicated in many patients. A better understanding of the HCV biology, immunopathology, and liver disease will help to design better therapeutic strategies. The American Association for the Study of Liver Diseases sponsored a single-topic conference on hepatitis C virus infection on March 4 and 5, 2005, to enhance our current knowledge in the areas of basic and clinical research related to antiviral and immunomodulatory therapies in hepatitis C disease. The faculty consisted of 23 invited experts in the field of viral hepatitis. The program was divided into four sections including: (a) replicative mechanisms and models; (b) viral-host interactions; and (c) antiviral drug development and new strategies; and (d) back to the bedside-current issues. This report summarizes each of the presentations sections. PMID- 17333352 TI - Inhibitory activities and attenuated expressions of 5-LOX with red ginseng in Helicobacter pylori-infected gastric epithelial cells. AB - Our recent studies documented that red ginseng extract (RGE, isolates from steamed and dried Panax ginseng, C.A. Meyer) can inhibit Helicobacter pylori induced mitogen-activated protein kinase (MAPK) signaling with repressing either nuclear factor (NF)-kappaB-DNA binding activity or releases of IL-8 and COX-2 in gastric epithelial cells (Dig Dis Sci 50:1218-1227, 2005). We extended the experiment to prove whether RGE influences 5-lipoxygenase (5-LOX) pathway, thereby suppressing the biosynthesis of 5(S)-HETE. The 5-LOX enzyme activities were measured by thin layer chromatography using (14)C-labeled arachidonic acid (AA) and quantified by reverse phase-high performance liquid chromatography in human gastric adenocarcinoma (AGS) cells cocultured with H pylori (ATCC 43504 strain) with or without pretreatment of RGE. Western blotting analyses for MAPK signaling and 5-LOX, reverse transcriptase polymerase chain reaction for interleukin-8, and electrophoretic mobility shift assay for NF-kappaB-DNA binding were done, respectively. H pylori infection increased exclusively 5-LOX enzyme activity and RGE inhibited H pylori-stimulated 5-LOX activity, resulting in suppression of 5(S)-HETE generations from AA. RGE inactivated c-jun phosphorylation and repressed redox-sensitive transcriptional activation, led to reduced expression of IL-8 and 5-LOX mRNA in gastric mucosal cells, of which action was very similar to known LOX inhibitor, 200 mumol of geraniin. RGE could be phytoceutical against H pylori infection-associated gastric inflammation through its LOX-inhibiting actions, inhibitory 5-LOX enzyme activity, and attenuating its expression. PMID- 17333353 TI - Endoscopic therapy of hepatic hydatid cyst disease in preoperative and postoperative settings. AB - The most common and serious complication of hepatic hydatid cyst disease is the communication between the cyst and the biliary tree. The diagnosis and treatment of this condition poses various difficulties. Data from patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for hydatid cysts communicating with the bile ducts either in the preoperative or postoperative setting over a 2-year period have been analyzed. In the preoperative group (n=41), jaundice (n=18), biliary colic (n=11), and cholangitis (n=10) were the most common presentations. On the other hand, the most common indication for ERCP in the postoperative group (n=69) was biliocutaneous leaks (n=60) and cholangitis (n=9). All but 2 patients in the preoperative group were treated by endoscopic sphincterotomy and/or extraction of hydatid cyst remnants followed by the placement of nasobiliary drainage catheter for the patients who had filling defects on cholangiogram. Subsequently, these patients were referred for surgery. ERCP was a definitive treatment for the remaining 2 patients. Endotherapy was successful for the patients who developed leak or had cyst remnants following surgery, whereas long-term biliary stenting was required for those who developed bile duct stenosis. There was no ERCP-associated complication, except mild pancreatitis in a single patient and self-limited hemorrhage in 2 patients. ERCP is an efficacious and safe method for the diagnosis and management of biliary complications associated with hydatid cyst disease. PMID- 17333354 TI - Celiac disease presenting in the postpartum period. PMID- 17333355 TI - Role of ghrelin and leptin in predicting the severity of acute pancreatitis. AB - Ghrelin and leptin are the hormones that influence endocrine and exocrine functions of the pancreas and regulate feeding behaviors and energy metabolism. The aim of this study was to investigate the levels of ghrelin and leptin in pancreatitis of different severities and the relation of these hormones with blood glucose level and proinflammatory cytokines. The study was performed on 90 Wistar Albino rats. Three experimental groups composed of 30 rats were established: control group, 0.9% NaCl solution was injected intraperitoneally (i.p); acute edematous pancreatitis (AEP) group, 1 microg/100 g cerulein was injected i.p. five times, at 1-hr intervals; and acute necrotizing pancreatitis (ANP) group, 500 mg/100 g L-arginine was injected i.p. Ten animals in each group were sacrificed under anesthesia 12, 24 and 48 hr after the last injection. After blood withdrawal, the pancreas was totally excised. The levels of blood sugar, lipase, serum tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL 1beta), ghrelin, and leptin were investigated and histopathologic examination was performed. Following pancreatitis induction, serum ghrelin levels increased at 24 hr and reached the peak level at 48 hr. Its level in the AEP group was higher than in the ANP group. Serum leptin levels in the AEP and ANP groups increased after 12 hr and stayed at high levels until 48 hr compared with the control group. Similarly to ghrelin and leptin, blood glucose levels increased in both pancreatitis groups, but the increase was more prominent in the ANP group, with levels >200 mg/ml at 48 hr. The levels of TNF-alpha and IL-1beta in the AEP and ANP groups reached the peak level at 24 hr and then decreased to a level close to that of the control group at 48 hr. We conclude that serum leptin and ghrelin levels increase in the first 48 hr of AEP and ANP. As the serum ghrelin levels in ANP are higher than in AEP, it can be used as a marker to show the severity of pancreatitis. While TNF-alpha and IL-1beta can be used as a prognostic factor in the first 24 hr, ghrelin and leptin can be used subsequently. PMID- 17333356 TI - Changes in GM1 ganglioside content and localization in cholestatic rat liver. AB - (Glyco)sphingolipids (GSL) are believed to protect the cell against harmful environmental factors by increasing the rigidity of plasma membrane. Marked decrease of membrane fluidity in cholestatic hepatocytes was described but the role of GSL therein has not been investigated so far. In this study, localization in hepatocytes of a representative of GSL, the GM1 ganglioside, was compared between of rats with cholestasis induced by 17alpha-ethinylestradiol (EE) and vehicle propanediol treated or untreated animals. GM1 was monitored by histochemical reaction employing cholera toxin B-subunit. Our findings in normal rat liver tissue showed that GM1 was localized in sinusoidal and canalicular hepatocyte membranes in both peripheral and intermediate zones of the hepatic lobules, and was nearly absent in central zones. On the contrary, in EE-treated animals GM1 was also expressed in central lobular zones. Moreover, detailed densitometry analysis at high magnification showed greater difference of GM1 expression between sinusoidal surface areas and areas of adjacent cytoplasm, caused as well by increased sinusoidal staining in central lobular zone as by decreased staining in cytoplasm in peripheral zone. These differences correlated with serum bile acids as documented by linear regression analyses. Both GM1 content and mRNA corresponding to GM1-synthase remained unchanged in livers; the enhanced expression of GM1 at sinusoidal membrane thus seems to be due to re distribution of cellular GM1 at limited biosynthesis and could be responsible for protection of hepatocytes against harmful effects of bile acids accumulated during cholestasis. PMID- 17333357 TI - Biochemical and functional characterization of cation dependent (Mr 46,000) goat mannose 6-phosphate receptor. AB - The Mannose 6-phosphate receptor (MPR's) proteins are important for transporting lysosomal enzymes from trans-golgi to the pre-lysosomal compartment. These are conserved in the vertebrates from fish to mammals. We have cloned the full length cDNA for the goat MPR 46 protein and compared its sequences to the other known vertebrate MPR 46 proteins. In the present study the full-length cDNA for the goat MPR 46 protein was expressed in MPR deficient cells. The expressed protein was purified on the multivalent phosphomannan gel in the presence of divalent metal ions. The apparent molecular mass of the expressed protein was found to be approximately 46 kDa and also exhibits oligomeric nature as observed in the other species, by using an MSC1 antibody (that recognizes the MPR 46 from molluscs to mammals) as well as with a peptide specific antibody corresponding to amino acid residues (218-237) of the cytoplasmic tail of human MPR 46 protein. Furthermore the distribution of the expressed protein was visualized by immunofluorescence using MSC1 and LAMP1 antibody. Additionally in the goat MPR 46 expressing cells, the sorting function of the expressed protein to sort cathepsin D to lysosomes was studied by confocal microscopy using cathepsin D antiserum and LAMP1 antibody. The binding of goat MPR 46 to cathepsin D was shown in far Western blotting and the mannose 6-phosphate dependent binding was shown by co immunoprecipitation. PMID- 17333358 TI - MR spectroscopy in heart failure--clinical and experimental findings. AB - Magnetic resonance spectroscopy (MRS) allows for the non-invasive detection of a wide variety of metabolites in the heart. To study the metabolic changes that occur in heart failure, (31)P- and (1)H-MRS have been applied in both patients and experimental animal studies. (31)P-MRS allows for the detection of phosphocreatine (PCr), ATP, inorganic phosphate (Pi) and intracellular pH, while (1)H-MRS allows for the detection of total creatine. All these compounds are involved in the regulation of the available energy from ATP hydrolysis via the creatine kinase (CK) reaction. Using cardiac MRS, it has been found that the PCr/CK system is impaired in the failing heart. In both, patients and experimental models, PCr levels as well as total creatine levels are reduced, and in severe heart failure ATP is also reduced. PCr/ATP ratios correlate with the clinical severity of heart failure and, importantly, are a prognostic indicator of mortality in patients. In addition, the chemical flux through the CK reaction, measured with (31)P saturation transfer MRS, is reduced more than the steady state levels of high-energy phosphates in failing myocardium in both experimental models and in patients. Experimental studies suggest that these changes can result in increased free ADP levels when the failing heart is stressed. Increased free ADP levels, in turn, result in a reduction in the available free energy of ATP hydrolysis, which may directly contribute to contractile dysfunction. Data from transgenic mouse models also suggest that an intact creatine/CK system is critical for situations of cardiac stress. PMID- 17333359 TI - The Early Risers preventive intervention: testing for six-year outcomes and mediational processes. AB - We examined effects of the Early Risers "Skills for Success" early-age-targeted prevention program on serious conduct problems following 5 years of continuous intervention and one year of follow-up. We also examined if intervention effects on proximally-targeted variables found after 3 years mediated intervention effects on conduct problems found after 6 years. Participants included 151 at risk children (106 males and 45 females) followed from first through sixth-grade, from 23 semi-rural schools in Minnesota. After 6 years, program children showed fewer oppositional defiant disorder (ODD) symptoms than control children. Program children did not significantly differ from controls on number of conduct disorder (CD) symptoms, DSM-IV diagnoses of ODD and CD, or drug use involvement. Results of the mediation analysis indicated that fewer ODD symptoms among program youth after 6 years were partially mediated by social skills and effective discipline. The study provides support for the early-starter model of conduct problems development that provides the framework for the Early Risers intervention. The study's implications for prevention and limitations are discussed. PMID- 17333360 TI - Violence exposure and psychopathology in urban youth: the mediating role of posttraumatic stress. AB - Understanding the mechanisms underlying the development of violence exposure sequelae is essential to providing effective treatments for traumatized youth. This longitudinal study examined the mediating role of posttraumatic stress in the relationship between violence exposure and psychopathology, and compared the mediated models by gender. Urban adolescents (n=1,358) were surveyed using the Social and Health Assessment. The proposed relationships were examined using Structural Equation Modeling. Posttraumatic stress fully mediated the relationships between victimization and depression and anxiety in girls, and partially so in boys. In addition, posttraumatic stress partially mediated the relationships between violence exposure and commission of violence in boys. Current findings support the longitudinal effects of violence exposure on adolescent mental health. Posttraumatic stress represents a unique mechanism for the development of psychopathology in girls and is also related to negative outcomes in boys. These findings have direct implications for prevention and rehabilitation efforts among violence exposed youth. PMID- 17333361 TI - Parenting, family loneliness, and peer functioning in boys with attention deficit/hyperactivity disorder. AB - The goal of the present study was to consider the associations between family functioning (parenting and family loneliness) and peer functioning in a sample of boys with ADHD (N = 110) and their mothers (N = 108) and fathers (N = 53). Results indicated that higher paternal warmth was associated with more peer acceptance, less peer rejection, and less problematic social behavior, but only for boys who reported low levels of family loneliness. In addition, more paternal power assertion was related to less peer acceptance, but only for boys who reported low levels of family loneliness. Maternal warmth and power assertion were not significantly related to boys' peer functioning. We discuss these findings in the context of the processes by which parenting may affect the peer relationships of these children. PMID- 17333362 TI - Modeling rater disagreement for ADHD: are parents or teachers biased? AB - The present study is the first to utilize twin modeling to examine whether parent teacher disagreement for ADHD ratings is due to parent or teacher bias, or due to raters observing different but valid ADHD behaviors. A joint analysis was conducted with 106 twin pairs, including twins selected for ADHD and control twin pairs. Total ADHD scores were analyzed using multiple rater models that estimate genetic and environmental contributions common to both raters and unique to each rater. Results suggest that 1) disagreement in ADHD ratings is strongly due to parents and teachers observing different ADHD behaviors, some of which is valid and some of which is due to bias, and 2) parents may be more biased than teachers in their ADHD ratings. PMID- 17333363 TI - Behavioral outcomes of Parent-Child Interaction Therapy and Triple P-Positive Parenting Program: a review and meta-analysis. AB - We conducted a review and meta-analyses of 24 studies to evaluate and compare the outcomes of two widely disseminated parenting interventions-Parent-Child Interaction Therapy and Triple P-Positive Parenting Program. Participants in all studies were caregivers and 3- to 12-year-old children. In general, our analyses revealed positive effects of both interventions, but effects varied depending on intervention length, components, and source of outcome data. Both interventions reduced parent-reported child behavior and parenting problems. The effect sizes for PCIT were large when outcomes of child and parent behaviors were assessed with parent-report, with the exclusion of Abbreviated PCIT, which had moderate effect sizes. All forms of Triple P had moderate to large effects when outcomes were parent-reported child behaviors and parenting, with the exception of Media Triple P, which had small effects. PCIT and an enhanced version of Triple P were associated with improvements in observed child behaviors. These findings provide information about the relative efficacy of two programs that have received substantial funding in the USA and Australia, and findings should assist in making decisions about allocations of funding and dissemination of these parenting interventions in the future. PMID- 17333364 TI - Comparison of c-DNA microarray analysis of gene expression between eutopic endometrium and ectopic endometrium (endometriosis). AB - PROBLEM: As recent studies have suggested abnormalities in the regulation of specific genes in the development of endometriosis, we investigated differentially expressed genes in endometriosis compared to endometrium. METHOD OF STUDY: Gene expression profiles using the Atlas microarray were performed in endometriotic tissue and endometrium. Nine of the 13 genes of endometriotic tissue showed an up-regulation in relation to endometrium and four of the 13 genes a down-regulation. RESULTS: Of the 1176 genes on the Atlas Human 1,2 array, only 13 differentially expressed identical genes were detected after repeating the gene analysis three times. CONCLUSION: According to our c-DNA analysis some differentially expressed genes may be involved in the pathogenesis of endometriosis. An imbalance in the genes responsible for the reproductive process may lead to a decrease in embryo implantation in patients with endometriosis. PMID- 17333365 TI - Preimplantation genetic diagnosis: present and future. AB - PURPOSE: Preimplantation genetic diagnosis (PGD) was developed more than a decade ago and aims to identify embryos free of genetic disease attributed either to gene mutations or chromosome errors. The purpose of this article is to provide an update on the current status and future prospects of PGD. METHODS: Review of studies employing different strategies for the detection of single gene defects, and chromosome abnormalities, both structural and numerical in the context of PGD. RESULTS: Amplification of several DNA fragments is feasible via multiplex PCR for the PGD of single gene disorders, whilst current FISH protocols employ up to 10 probes to identify embryos with a normal chromosome complement. New methods are being developed which will enable the assessment of the entire chromosome complement of embryonic blastomeres. CONCLUSIONS: PGD has come a long way since its first application, and has become very accurate and reliable. Technical advances in the field of preimplantation genetics mean that PGD holds great promise for the future. PMID- 17333366 TI - The utility of serum leptin and follicular fluid leptin, estradiol, and progesterone levels during an in vitro fertilization cycle. AB - PURPOSE: To prospectively evaluate serum and follicular fluid leptin, estradiol, and progesterone levels during in vitro fertilization. METHODS: Prospective observational study measuring serum levels at six points during the IVF cycle and follicular fluid at the time of retrieval. RESULTS: Serum leptin and estradiol levels both significantly increased for the individual patients during the IVF stimulation process. None of the leptin levels differed based on pregnancy outcome. BMI significantly correlated with all leptin levels. Follicular fluid estradiol correlated with serum estradiol only in pregnant patients (r = 0.97, p<0.01) and was unrelated in non-pregnant patients (r=-0.15, p=0.81). CONCLUSION: Serum and follicular leptin levels are highly correlated. Leptin levels increase during the IVF cycle and vary between patients based on maternal BMI, but do not correlate with other serum hormone levels or pregnancy outcome. Pregnancy outcome success was reflected in the relationship between follicular fluid and serum levels of estradiol, independent of leptin levels. PMID- 17333367 TI - Sudden cardiac death: epidemiologic and financial worldwide perspective. AB - The term sudden cardiac death (SCD) implies the sudden and unexpected loss of an active, productive member of the community. SCD is typically attributed to lethal ventricular arrhythmias; however, these arrhythmias are impossible to diagnose after the fact. Epidemiologic analyses, therefore, rely on inference of the cause of death. Estimates of the incidence of are SCD variable but it may be as high as 1 per 1,000 per year. The cost of SCD to society is incalculable. Current strategies for preventing SCD rely on risk assessment for cardiology patients and implantation of defibrillators (ICD) in high risk patients. Unfortunately, the absolute number of SCDs that occur in the general (relatively low-risk) population is large compared to the number of SCDs in the high risk population. Therefore, prevention of SCD in high risk populations is unlikely to prevent the majority of SCDs. Cost-effectiveness of ICD implantation for prevention of SCD has been studied; ICDs appear to meet U.S. and European criteria for cost effectiveness if their benefit extends to at least 7-8 years. However, therapies considered cost-effective may nonetheless be too costly for most worldwide societies. Currently, investigators are focusing on refining risk stratification, partly in hopes of identifying patients for whom ICD implantation will not be useful. PMID- 17333368 TI - Are women worldwide under-treated with regard to cardiac resynchronization and sudden death prevention? AB - Implantable cardioverter defibrillators (ICDs) have been demonstrated to improve survival in patients with serious structural heart disease. Likewise, cardiac resynchronization therapy (CRT) has assumed an important role in the treatment of patients with symptomatic heart failure because of its demonstrated value in improving functional class, quality of life, exercise capacity, and survival. However, these clinical trials have all primarily enrolled Caucasian males, raising the question as to whether other important subgroups benefit in a comparable way. Women have lower rates of sudden cardiac death (SCD) compared to men, and event rates lag 10-20 years behind those in men. Among patients with known coronary artery disease, women have one-fourth the risk of SCD found in men. Women with heart failure tend to present at an older age than men, and women more often have heart failure with preserved systolic function, a group in whom prophylactic ICD therapy for the prevention of SCD has not been studied. Despite these differences, analysis of clinical trial results shows that women have similar outcomes with ICD and CRT therapy compared to men. There is a lower percentage of women among device therapy patients both in clinical trials and in practice for reasons that are not clear, but at least some of the difference is likely due to differences in age at presentation and co-morbidities. In fact, device therapy overall appears to be under-utilized in both men and women, when implantation rates are compared to the prevalence of heart failure in the population as a whole. PMID- 17333369 TI - Catheter selection for ablation of the cavotricuspid isthmus for treatment of typical atrial flutter. AB - Radiofrequency catheter ablation (RFA) represents the first line therapy of the cavotricuspid isthmus-dependent atrial flutter (CTI-AFL) with a high efficacy and low secondary effects. RFA of CTI-dependent AFL can be performed by using various types of ablation catheters. Recent evaluations comparing externally cooled tip RFA (ecRFA) catheters and large-tip (8 mm) catheters have revealed that these catheters have a higher efficacy for CTI-AFL ablation compared to 4-mm catheters. The reliability of RFA catheters for AFL is variable and an optimal catheter selection may enhance the RFA effectiveness. The main goal of this article is to review the elements that improve the management of CTI RFA. Preliminary examinations of histopathologic and anatomical elements that may interfere with conventional CTI RFA are presented. Experimental studies concerning the electrobiology of large-tip and cooled-tip catheters are compared. The different catheter designs between cooled-tip and 8-mm-tip catheters are examined (size of the deflectable curve, rotation stability, and size of the distal nonsteerable catheter part) because of their critical role in CTI RFA results. A thorough review of clinical trials of each catheter is presented, and comparison of both catheters in this clinical setting is analyzed. In addition, the role of CTI morphology on AFL RF duration is underlined such as the value of right atrial angiography as an adjunct tool for CTI RFA catheter selection. Based on randomized studies, 8-mm-tip catheters seem to be more effective for ablation in case of straight angiographic isthmus morphology. On the other hand, ecRFA catheters appear to be more effective in cases of complex CTI anatomy or difficult CTI RFA. To reduce X-ray exposition and RFA application time, few studies report that CTI angiographic evaluation before RFA allows a catheter selection based on both CTI morphology and length. Moreover, preliminary data of randomized studies showed that an angiographic isthmus evaluation may predict both the effectiveness of a RFA catheter and the risk of an expensive catheter crossover. PMID- 17333370 TI - Courtship pheromones in parasitic wasps: comparison of bioactive and inactive hydrocarbon profiles by multivariate statistical methods. AB - Cuticular hydrocarbons play a significant role in the regulation of cuticular permeability and also in the chemical communication of insects. In the parasitoid Lariophagus distinguendus (Hymenoptera: Pteromalidae), male courtship behavior is mediated by a female-produced sex pheromone. Previous studies have shown that the chemicals involved are already present in the pupal stage of both males and females. However, pheromonal activity in males decreases shortly after emergence. This pheromonal deactivation occurs only in living males, suggesting an active process rather than simple evaporation of bioactive compounds. Here, we present evidence that the sex pheromone of L. distinguendus is composed of a series of cuticular hydrocarbons. Filter paper disks treated with nonpolar fractions of cuticular extracts of freshly emerged males and females, 72-hr-old females, and yellowish pupae caused arrestment and stimulated key elements of courtship behavior in males, whereas fractions of 72-hr-old males did not. Sixty-four hydrocarbons with chain length between C(25) and C(37) were identified in the fractions by gas chromatography-mass spectrometry (GC-MS). Methyl-branched alkanes with one to four methyl groups were major components, along with traces of n-alkanes and monoalkenes. Principal component analysis, based on the relative amounts of the compounds, revealed that cuticular hydrocarbon composition differed among all five groups. By using partial least squares-discriminant analysis, we determined a series of components that differentiate bioactive and bioinactive hydrocarbon profiles, and may be responsible for pheromonal activity of hydrocarbon fractions in L. distinguendus. PMID- 17333371 TI - A Comparison of Semiochemically Mediated Interactions Involving Specialist and Generalist Brassica-feeding Aphids and the Braconid Parasitoid Diaeretiella rapae. AB - Diaeretiella rapae, a parasitoid that predominately specializes in the parasitism of Brassica-feeding aphids, attacks Lipaphis erysimi, a specialist feeding aphid of the Brassicaceae and other families in the Capparales, at a greater rate than the generalist-feeding aphid, Myzus persicae. In this study, we investigated the orientation behavior of D. rapae to the volatile chemicals produced when these two aphid species feed on turnip (Brassica rapa var rapifera). We showed no significant preference orientation behavior to either aphid/turnip complex over the other. Isothiocyanates are among the compounds emitted by plants of the Brassicaceae in response to insect feeding damage, including by aphids. We assessed parasitoid orientation behavior in response to laboratory-formulated isothiocyanates. We tested two formulations and discovered significant orientation toward 3-butenyl isothiocyanate. We also assessed plant and aphid glucosinolate content, and showed large levels of glucosinolate concentration in L. erysimi, whereas there was little change in plant content in response to aphid feeding. Our results suggest that during the process of host location, similar cues may be utilized for locating L. erysimi and M. persicae, whereas the acceptance of hosts and their suitability may involve aspects of nonvolatile aphid chemistry. PMID- 17333372 TI - Species-specific expression of major urinary proteins in the house mice (Mus musculus musculus and Mus musculus domesticus). AB - The analysis of expression of pheromone-carrying major urinary proteins (MUPs) from two subspecies of house mice (Mus m. musculus, Mus m. domesticus) was studied. It has been previously shown that commensal populations of the two subspecies can discriminate on the basis of urinary signals. MUPs are predominant urinary proteins that protect pheromones from rapid degradation in a hydrophilic environment, and individuals of M. m. musculus tend to rely on these urinary cues in the process of subspecies discrimination more than M. m. domesticus individuals. Although it is not precisely known what triggers phenotypic and epigenetic changes of MUP expression, our results show that in the subspecies M. m. musculus, sex is a significant factor influencing variations in the regulation of selected MUPs in the liver. Furthermore, male M. m. musculus individuals expressed all the studied MUPs' mRNA significantly more than females or individuals of either sex in M. m. domesticus. Correspondingly, the pattern of mRNA abundance was corroborated with the level of total MUP concentration in the urine, such that the level of sexual dimorphism was also significant and species specific. Our finding introduces a hypothesis that quantitative variation of these proteins may be an essential part of a subspecies recognition system that maintains homospecific mixing. PMID- 17333373 TI - Alkaloids in bufonid toads (melanophryniscus): temporal and geographic determinants for two argentinian species. AB - Bufonid toads of the genus Melanophryniscus represent one of several lineages of anurans with the ability to sequester alkaloids from dietary arthropods for chemical defense. The alkaloid profile for Melanophryniscus stelzneri from a location in the province of Cordoba, Argentina, changed significantly over a 10 year period, probably indicating changes in availability of alkaloid-containing arthropods. A total of 29 alkaloids were identified in two collections of this population. Eight alkaloids were identified in M. stelzneri from another location in the province of Cordoba. The alkaloid profiles of Melanophryniscus rubriventris collected from four locations in the provinces of Salta and Jujuy, Argentina, contained 44 compounds and differed considerably between locations. Furthermore, alkaloid profiles of M. stelzneri and M. rubriventris strongly differed, probably reflecting differences in the ecosystem and hence in availability of alkaloid-containing arthropods. PMID- 17333374 TI - Intraspecific variation in aphid resistance and constitutive phenolics exhibited by the wild blueberry Vaccinium darrowi. AB - Illinoia pepperi (MacGillivray) infests cultivated highbush blueberries, Vaccinium corymbosum L., in the Northeastern United States. Allopatric resistance to I. pepperi was examined in Vaccinium darrowi Camp, which evolved in the absence of I. pepperi in the Southeastern U.S. V. corymbosum cv. "Elliott", was used as a susceptible control. Between population variability in I. pepperi resistance was assessed by measuring length of the prereproductive period, fecundity, and survivorship on 14 V. darrowi accessions representing 11 discrete wild populations. Length of I. pepperi's prereproductive period and survivorship were not significantly affected. However, differences were detected in fecundity and the intrinsic rate of increase (r ( m )). Within population variability in resistance was measured by confining first instars to 24 accessions from a single wild population of V. darrowi (NJ88-06). Significant differences in the mean total number of aphids occurring after 20 d were only detected between 2 of the 24 V. darrowi accessions. A greater degree of diversity in I. pepperi resistance exists between populations of V. darrowi compared to within a population. Constitutive leaf and stem polyphenolics were identified by HPLC-MS and quantified from 14 of the V. darrowi accessions. The accessions varied in concentrations of five phenolic acids and seven flavonol glycosides, but a correlation was not found between individual or total phenolics and aphid performance. Overall, screening within and between populations of V. darrowi identified promising sources of aphid resistance, but phenolic acid and flavonol glycoside profiles did not predict resistance levels. The mechanism of resistance remains to be identified. PMID- 17333375 TI - Ozone degrades common herbivore-induced plant volatiles: does this affect herbivore prey location by predators and parasitoids? AB - Inducible terpenes and lipoxygenase pathway products, e.g., green-leaf volatiles (GLVs), are emitted by plants in response to herbivory. They are used by carnivorous arthropods to locate prey. These compounds are highly reactive with atmospheric pollutants. We hypothesized that elevated ozone (O(3)) may affect chemical communication between plants and natural enemies of herbivores by degrading signal compounds. In this study, we have used two tritrophic systems (Brassica oleracea-Plutella xylostella-Cotesia plutellae and Phaseolus lunatus Tetranychus urticae-Phytoseiulus persimilis) to show that exposure of plants to moderately enhanced atmospheric O(3) levels (60 and 120 nl l(-1)) results in complete degradation of most herbivore-induced terpenes and GLVs, which is congruent with our hypothesis. However, orientation behavior of natural enemies was not disrupted by O(3) exposure in either tritrophic system. Other herbivore induced volatiles, such as benzyl cyanide, a nitrile in cabbage, and methyl salicylate in lima bean, were not significantly reduced in reactions with O(3). We suggest that more atmospherically stable herbivore-induced volatile compounds can provide important long-distance plant-carnivore signals and may be used by natural enemies of herbivores to orientate in O(3)-polluted environments. PMID- 17333376 TI - Systemin regulates both systemic and volatile signaling in tomato plants. AB - The prevailing reaction of plants to pest attack is the activation of various defense mechanisms. In tomato, several studies indicate that an 18 amino acid (aa) peptide, called systemin, is a primary signal for the systemic induction of direct resistance against plant-chewing pests, and that the transgenic expression of the prosystemin gene (encoding the 200 aa systemin precursor) activates genes involved in the plant response to herbivores. By using a combination of behavioral, chemical, and gene expression analyses, we report that systemin enhances the production of bioactive volatile compounds, increases plant attractivity towards parasitiod wasps, and activates genes involved in volatile production. Our data imply that systemin is involved in the systemic activation of indirect defense in tomato, and we conclude that a single gene controls the systemic activation of coordinated and associated responses against pests. PMID- 17333377 TI - Evaluation of the evolution of increased competitive ability (EICA) hypothesis: loss of defense against generalist but not specialist herbivores. AB - The evolution of increased competitive ability (EICA) hypothesis predicts that invasive plant species may escape their specialized natural enemies in their introduced range and subsequently evolve with a decrease in investment in anti herbivore chemical defenses relative to native conspecifics. We compared the chemical profile of 10 populations of US native and 20 populations of European invasive Solidago gigantea. To test for differences in inducibility between native and invasive populations, we measured secondary chemistry in both damaged and undamaged plants. We also performed bioassays with three specialist and two generalist insect herbivores from four different feeding guilds. There was no evidence that invasive populations had reduced concentrations of sesquiterpenes, diterpenes, or short-chain hydrocarbons (SCH), although significant variation among populations was detected. Sesquiterpene and diterpene concentrations were not influenced by damage to the host plant, whereas SCH concentrations were decreased by damage for both native and invasive plants. Performance of the three specialist insects was not affected by the continental origin of the host plant. However, larval mass of the generalist caterpillar Spodoptera exigua was 37% lower on native plants compared to invasive plants. The other generalist insect, a xylem-tapping spittlebug that occurs on both continents, performed equally well on native and invasive plants. These results offer partial support for the defense predictions of the EICA hypothesis: the better growth of Spodoptera caterpillars on European plants shows that some defenses have been lost in the introduced range, even though our measures of secondary chemistry did not detect differences between continents. Our results show significant variation in chemical defenses and herbivore performance across populations on both continents and emphasize the need for analysis across a broad spatial scale and the use of multiple herbivores. PMID- 17333378 TI - Unstable embodiments: a phenomenological interpretation of patient satisfaction with treatment outcome. AB - Many patients experience aspects of treatment and care as dehumanizing because the body is considered separate from the self and its life context. An attempt to transcend viewing persons in dualistic terms is posed by phenomenologists who focus not on "the body" as such but on what it means to be "embodied." In this paper, we review the relevance of the phenomenology of the body for health care and report the results of comparing Sally Gadow's phenomenological insights about body-self unity with a qualitative analysis of patients' accounts of satisfaction with the outcome of hand surgery. We illustrate the ways in which our findings were and were not congruent with Gadow's conceptualization of embodiment and highlight aspects that are ambiguous. We conclude that the body-self dialectical relationship should be recast as a body-self-society trialectic and discuss the implications of this new conceptualization for clinical practices. PMID- 17333379 TI - Work factors related to psychological and health-related distress among employees with chronic illnesses. AB - OBJECTIVE: This study examined specific psychosocial factors associated with psychological and health-related distress amongst employees reporting different chronic illnesses. METHODS: The sample consisted of 1029 employees managing either musculoskeletal pain (n=324), arthritis and rheumatism (n=192), asthma (n=174), depression and anxiety (n=152), heart disease (n=96) or diabetes (n=91). Information on psychological distress, work limitations, illness management, disclosure, absence, presenteeism, support and demographic factors were obtained through self-administered questionnaires. RESULTS: Both low psychological well being and high health-related distress were associated with an increase in work limitations (beta=0.20, SE=.03; and beta=0.19, SE=.01, respectively), poorer management of illness symptoms at work (beta=-0.17, SE=.12; and beta=-0.13, SE=.02), high presentieesm (beta=0.19, SE=.25; and beta=0.14, SE=.05) and low workplace support (beta=-0.05, SE=.22; and beta=-0.12, SE=.05). Health-related distress was additionally associated with disclosure of illness at work (beta=0.18, SE=.08) and long-term sickness absence (beta=0.10, SE=.06). CONCLUSIONS: To enable individuals to effectively manage both their illness and their work without serious repercussions, it is important for both healthcare professionals and employers alike, to improve the well-being of workers with chronic illness by supporting and facilitating their efforts to over-come health related limitations at work. PMID- 17333380 TI - Lower back problems and work-related risks in a South African manganese factory. AB - An analytical cross-sectional epidemiological study carried out among 109 manganese plant workers aimed to examine the prevalence and association between lower back problems (LBP) and occupational risk factors. Outcome was defined using a guided questionnaire and a functional rating index. Exposure to occupational risk factors was determined using self-reported questionnaires and workstation analyses. Multivariate logistic regression analyses indicated significant adjusted odds ratios (OR) for prolonged 90 degrees trunk flexion (OR 2.16; CI 1.15-4.05); manual handling (1.89; 1.17-3.08); load carriage (1.54; 1.08 2.19); and lifting (4.61; 1.37-15.47). The findings illustrate regional and occupational specifics of risk for LBP, and indicate that self-selection or adaptation to task-specific demands could possibly lead to observations of ergonomically relevant risk factors, which do not necessarily yield statistically significant associations with LBP. The findings further support multi-modal preventative approaches. PMID- 17333381 TI - Addressing the challenges and opportunities for today's youth: toward an integrative model and its implications for research and intervention. AB - This article calls for, and proposes some tenets of, model building in adolescent psychosocial development. Specifically, it is suggested that there is a need for a model that draws from the risk-protection approach, from which many prevention science approaches are drawn, and the applied developmental science perspective, from which many positive youth development approaches are drawn. The model to be built, and the integration it proposes, is based in the overlap between protective factors and developmental assets (drawn from the applied developmental science and positive youth development perspectives), as well as on the complementarity of the intrapersonal mechanisms proposed within the two perspectives. The article also poses important questions for future research and presents an empirical agenda for addressing these questions in the service of building and testing a model of adolescent psychosocial development and of integrating the prevention and positive youth development approaches to intervention and policy. PMID- 17333382 TI - Altering key characteristics of a disseminated effective behavioral intervention for HIV positive adults: the "healthy relationships" experience. AB - HIV prevention programs targeted to people living with HIV/AIDS are the US national HIV prevention priority. Healthy Relationships is a nationally disseminated HIV prevention program for HIV positive adults. Key characteristics of the intervention package include gender separated groups facilitated by a mental health professional and a HIV positive peer counselor, both of which cause considerable barriers to implementation. We examined an alteration of the original Healthy Relationships intervention (HR-O) that delivered the intervention to mixed gender groups by non-mental health and non-HIV positive facilitators. Process measures from the altered Healthy Relationships intervention (HR-A) were compared to the same measures taken in the HR-O trial. Intervention completion rates were better in the HR-A model (84%) than HR-O (70%). Results showed that HR-A was comparable to HR-O in social support, group cohesion, and group openness. Facilitators in HR-A were viewed somewhat more positive than in HR-O. We found no empirical basis for conducting separate groups by gender or for constraining the facilitators in terms of their professional and HIV statuses. Research is needed to test the assumptions of other evidence-based HIV prevention programs. PMID- 17333383 TI - Effect of workplace laughter groups on personal efficacy beliefs. AB - This study measured the impact of a purposeful aerobic laughter intervention on employees' sense of self-efficacy in the workplace. Participants were 33 employees of a behavioral health center. They met for 15-minute sessions on 15 consecutive workdays and engaged in a guided program of non-humor dependent laughter. The primary outcome measure was the Capabilities Awareness Profile, a self-report self-efficacy questionnaire. Employees demonstrated a significant increase in several different aspects of self-efficacy, including self regulation, optimism, positive emotions, and social identification, and they maintained these gains at follow-up. Purposeful laughter is a realistic, sustainable, and generalizable intervention that enhances employees' morale, resilience, and personal efficacy beliefs. PMID- 17333384 TI - Genetic counseling, insurance status, and elements of medical home: analysis of the national survey of children with special health care needs. AB - OBJECTIVE: To examine associations between receiving genetic counseling and the enabling factors of insurance and medical home. METHODS: This study uses data from the National Survey of Children with Special Health Care Needs (CSHCN). We use descriptive statistics to characterize families of CSHCN who needed and received genetic counseling as well as families who needed but did not receive genetic counseling. We conduct logistic regression to calculate the association between receiving genetic counseling, insurance status, and medical home while adjusting for child's age, mother's education, race, ethnicity, and severity of condition. RESULTS: Seven percent of families with CSHCN, representing 643,432 CSHCN nationwide, reported needing genetic counseling in 2001. Of those in need of genetic counseling, an estimated 123,117 CSHCN reported not receiving genetic counseling. Compared to CSHCN with continuous insurance coverage, CSHCN with interrupted insurance coverage and CSHCN without insurance are significantly less likely to receive genetic counseling. The odds of receiving genetic counseling by CSHCN with medical homes are 2.70 times higher compared to peers without medical homes (95% CI: 1.58, 4.61; p 2 mm. CONCLUSIONS: Melanoma will recur in approximately 9% of patients with tumor-negative SLNs. Patients with thick, ulcerated melanomas on the head or neck have the highest risk for recurrence. This group should be followed closely for recurrence and considered for adjuvant therapy. PMID- 17333419 TI - Macrophage-based anti-cancer therapy: modelling different modes of tumour targeting. AB - Tumour hypoxia is associated with poor drug delivery and low rates of cell proliferation, factors that limit the efficacy of therapies that target proliferating cells. Since macrophages localise within hypoxic regions, a promising way to target hypoxic tumour cells involves engineering macrophages to express therapeutic genes under hypoxia. In this paper we develop mathematical models to compare the responses of avascular tumour spheroids to two modes of action: either the macrophages deliver an enzyme that activates an externally applied prodrug (bystander model), or they deliver cytotoxic factors directly (local model). The models we develop comprise partial differential equations for a multiphase mixture of tumour cells, macrophages and extracellular fluid, coupled to a moving boundary representing the spheroid surface. Chemical constituents, such as oxygen and drugs, diffuse within the multiphase mixture. Simulations of both models show the spheroid evolving to an equilibrium or to a travelling wave (multiple stable solutions are also possible). We uncover the parameter dependence of the wave speed and steady-state tumour size, and bifurcations between these solution forms. For some parameter sets, adding extra macrophages has a counterintuitive deleterious effect, triggering a bifurcation from bounded to unbounded tumour growth. While these features are common to the bystander and local models, the crucial difference is where cell death occurs. The bystander model is comparable to traditional chemotherapy, with poor targeting of hypoxic tumour cells; however, the local mode of action is more selective for hypoxic regions. We conclude that effective targeting of hypoxic tumour cells may require the use of drugs with limited mobility or whose action does not depend on cell proliferation. PMID- 17333420 TI - Increased risk of relapse after breast cancer with exposure to organochlorine pollutants. PMID- 17333421 TI - Methyl isothiocyanate residential community air assessment for South Franklin County, Washington. PMID- 17333422 TI - Effects of ammonia on cellular biomarker responses in oysters (Crassostrea virginica). PMID- 17333423 TI - Volatile organic compound exposure of suburban elementary students in Taiwan. PMID- 17333424 TI - Postcapture depuration of essential metals in the deep sea hydrothermal mussel Bathymodiolus azoricus. PMID- 17333425 TI - Contents of trace metals in water and macroalgae along the Mediterranean coast of Tunisia. PMID- 17333426 TI - Bacterial diversity in mine tailings compared by cultivation and cultivation independent methods and their resistance to lead and cadmium. AB - To examine bacterial community composition in rhizosphere of plants colonizing on mine tailings and phylogenetic differences between subcommunities resistant to different metals, we constructed four clone libraries of 16S rDNA sequences. One was amplified directly from tailing microbial DNA (named as Ci library) and three from cultures on the plates containing of 0.5 mM CdCl(2) (Cd library), 2 mM Pb (NO(3))(2) (Pb library), and without any metals (Cw library). In total, nine bacterial divisions and two unclassified groups were identified from 352 clones of these libraries. Ci clones covered eight divisions, whereas all cultivable clones only covered four divisions. Thus, Ci library provided more phylogenetic diversity than cultivable libraries. However, the microbes represented by the cultivable clones were more similar to previously described bacteria than those represented by Ci clones. All Ci clones were not found in three cultivable libraries. Cd library were exclusively Gram-negative bacteria of Acinetobacter, Ralstonia, Comamonas, and Chryseobacterium. Meanwhile, dominant Gram-positive bacteria in Pb library, Paenibacillus and Bacillus, were also not found in Cd library. Our data indicate that phylogenetic structure was very different from those in acid mine drainage. Meanwhile, tailings harbored phylogenetically distinct subcommunities resistant to Pb and Cd. PMID- 17333427 TI - Seasonal influences on the ecology of testate amoebae (Protozoa) in a small Sphagnum peatland in southern Ontario, Canada. AB - Testate amoebae (Protozoa) were studied in spring, summer, and fall from the same microhabitats in a small Sphagnum-dominated peatland in southern Ontario, Canada. A total of 32 sampling stations were established in two wetland plant communities, 19 in an open Ericaceae low-shrub community and 13 in a closed Picea mariana and Larix laricina swamp community. Sphagnum was collected in each station for analysis of testate amoebae and measurement of soil water content parameters and water table depth in May, August, and October 2001. pH and dissolved oxygen of the groundwater under the Sphagnum were measured also. A total of 52 taxa including the rotifer, Habrotrocha angusticollis, were identified. Soil water content and water table variables emerged as the primary factors separating testate amoebae between the open bog/fen community and swamp community. Testate amoebae in the open bog/fen community showed a clear separation between the May sampling period and the August and October sampling periods. Sampling stations in May had much higher water table and were wetter than those in August and October. Conversely, testate amoebae in the swamp community did not show a clear difference between sampling periods. Soil moisture and water tables appear to be more constant in the swamp communities. Biological factors or other microscale environmental factors may need to be considered to explain seasonal changes in testate amoebae. A greater understanding of relationships between testate amoebae and microenvironmental factors is necessary to track seasonality in testate amoebae distributions. PMID- 17333428 TI - Microbial maintenance: a critical review on its quantification. AB - Microbial maintenance is an important concept in microbiology. Its quantification, however, is a subject of continuous debate, which seems to be caused by (1) its definition, which includes nongrowth components other than maintenance; (2) the existence of partly overlapping concepts; (3) the evolution of variables as constants; and (4) the neglect of cell death in microbial dynamics. The two historically most important parameters describing maintenance, the specific maintenance rate and the maintenance coefficient, are based on partly different nongrowth components. There is thus no constant relation between these parameters and previous equations on this subject are wrong. In addition, the partial overlap between these parameters does not allow the use of a simple combination of these parameters. This also applies for combinations of a threshold concentration with one of the other estimates of maintenance. Maintenance estimates should ideally explicitly describe each nongrowth component. A conceptual model is introduced that describes their relative importance and reconciles the various concepts and definitions. The sensitivity of maintenance on underlying components was analyzed and indicated that overall maintenance depends nonlinearly on relative death rates, relative growth rates, growth yield, and endogenous metabolism. This quantitative sensitivity analysis explains the felt need to develop growth-dependent adaptations of existing maintenance parameters, and indicates the importance of distinguishing the various nongrowth components. Future experiments should verify the sensitivity of maintenance components under cellular and environmental conditions. PMID- 17333429 TI - Power spectra analysis of levator veli palatini muscle electromyogram during velopharyngeal closure for swallowing, speech, and blowing. AB - The velopharynx closes during swallowing and pneumatic activities. Pneumatic closure, which is acquired, prevents expiratory air from passing into the nasal cavity, whereas during swallowing, velopharyngeal closure is achieved innately, preventing regurgitation into the nasal cavity. These findings suggest that velopharyngeal closure during swallowing is a different mechanism from that during pneumatic activity. The purpose of this study was to clarify activity differences of the levator veli palatini muscle during swallowing, speech, and blowing using power spectra analysis. Five normal adults served as subjects. Each subject was instructed to speak, blow, and swallow. Electromyograms of the levator muscle were recorded and the spectrum analyzed for each task to calculate the mean power frequency (MPF) of EMG signals. There was no significant difference in MPF between speech and blowing for all subjects. MPF was significantly greater during swallowing than during pneumatic activities for all subjects. The MPF value can reflect the composition of active motor units during muscle contraction. It was therefore indicated that the motor units of the levator muscle participating in contraction were different during swallowing and respiratory activities. PMID- 17333432 TI - Incidence and management of vaginal extrusion of acellular porcine dermis after incontinence and prolapse surgery. AB - We report our experience with vaginal extrusion of acellular porcine dermis in women undergoing pelvic reconstructive surgery. Over 5 years, 270 patients received a Pelvicol pubovaginal sling (PVS) or prolapse repair using interposition graft. Charts were retrospectively evaluated for evidence of graft extrusion, management, and outcomes. Chi-square analysis was conducted to evaluate the association of extrusion with perioperative variables. Nineteen women (7%) had partial or complete vaginal graft extrusion. After a PVS, 11 of 13 women healed by re-epithelialization and remained continent, while 2 required operative debridement. Four of six patients receiving interposition grafts healed after small incisional separations. Two women underwent additional surgery to address extensive extrusion, and both prolapses recurred. After statistical analysis, vaginal extrusion was significantly associated with PVS and concomitant urethral diverticulectomy. Small incisional separations frequently heal and cause no symptom recurrence. Larger areas of extrusion may require debridement and may contribute to recurrence of symptoms. PMID- 17333433 TI - Primary urethral transitional cell carcinoma presenting as a urethral caruncle. AB - Primary urethral neoplasm is an uncommon diagnosis, and carcinomas arising from urethral caruncle are rare. Optimal treatment guidelines are not available because of the limited number of diagnosed cases. However, an aggressive treatment approach is needed to provide the best chance of cure. PMID- 17333434 TI - Risk factors for uterine prolapse in Nepal. AB - Uterine prolapse is a significant public health problem in Nepal. The aim of this study was to determine the prevalence of uterine prolapse and to define possible risk factors for this disease in the Kathmandu Valley of Nepal. This clinical report consists of an analysis of data from Dr. Iwamura Memorial Hospital and Research Center (IMHARC) in Bhaktapur, between July 1 and September 30, 2006. This analysis was restricted to a sample that included all women with complaints of uterine prolapse (second- or third-degree prolapse) diagnosed and treated at the IMHARC. During a 3-month period, 96 women were diagnosed and treated with uterine prolapse. The median age at the time of clinical presentation was 50 years, and the median maternal weight was 45 kg. In average, the women gave birth to four children vaginally. Most of the affected women were smoking, and most of them were postmenopausal. Thirty-five percent of the affected patients had a chronic obstructive pulmonary disease (COPD), 16% suffered from hypertension and 5% had diabetes mellitus. The majority of the women with uterine prolapse were of Newari origin (84%), and nearly all patients reported that they were working heavily during pregnancy as well as in the postpartum period (87%). We found several risk factors for uterine prolapse in Nepal. Especially extensive physical labor during pregnancy and immediately after delivery, low availability of skilled birth attendants, smoking while having COPD and low maternal weight due to lack of nutritious food are mainly responsible for this common disease. In our opinion, extensive information, prevention programs and early management of genital prolapse should be the first steps to reduce this significant social and public health problem in Nepal. PMID- 17333435 TI - A safety and quality of life analysis of intravaginal slingplasty in female stress incontinence: a prospective, open label, multicenter, and observational study. AB - This prospective, open label, multicenter, and observational study was performed to determine the efficacy, safety, and the impact of this procedure on the current quality of life (QOL). One hundred three women underwent the intravaginal slingplasty (IVS) procedure. The postoperative evaluation consisted of clinical examination, Incontinence Quality of Life (I-QOL) questionnaire, 3-day consecutive frequency volume chart, free flowmetry, and measurement of post void residual. At 12 months, 83 patients have completed follow-up and are included in this analysis. Patient assessment of continence revealed 89.2% (74/83) cure rate. During follow-up period, one patient (1.2%) has presented with vaginal erosion of the sling material. The I-QOL showed significant improvement in total and three subscale scores at 12 months of follow-up period. This study demonstrated that the IVS procedure provides a safe and effective means for the treatment of female stress incontinence and improvement of QOL. PMID- 17333436 TI - Comparison of physician and patient assessments of incontinence severity and improvement. AB - Compare the subjective and objective assessment of stress urinary incontinence (SUI) severity and improvement with treatment using patient- and clinician-rated global impression of severity (PGI-S, CGI-S) and improvement (PGI-I, CGI-I) scales. Five hundred fifty-three women with mild SUI were recruited via media advertising into a placebo-controlled duloxetine trial. PGI-S and CGI-S (normal, mild, moderate, severe) were administered at baseline and PGI-I and CGI-I (seven responses from "very much worse" to "very much better") during treatment. Incontinence episode frequency (IEF) was determined from diaries. Agreements between clinician and patient ratings were assessed using Kappa and degree of association with Spearman's correlation. There was only a slight agreement regarding severity, with 53% of ratings being different (Kappa = 0.14; 95%CI = 0.08, 0.20). When ratings differed, clinicians rated severity worse in 72% of cases than did patients. Agreement regarding improvement was moderate, with 42% of ratings being different (Kappa = 0.45; 95%CI = 0.39, 0.50). When ratings differed, clinicians rated improvement greater than did patients in 54% of cases. Patients' assessments of severity correlated better with IEF (0.33) than did the clinicians' (0.15). The correlations of PGI-I and CGI-I with IEF changes were similar (0.46 and 0.44). In this study, the subjective (patient) and objective (clinician) assessments of SUI improvement with treatment appear to be more closely aligned than are the assessments of initial SUI severity. PMID- 17333437 TI - Influence of oxidative stress and alpha tocopherol supplementation on urothelial cells of the urinary bladder in ovariectomised rats. AB - The present study was designed to investigate whether vitamin E supplementation would influence the levels of oxidative stress and the damage to urothelial cell DNA in the bladders of castrated rats. A total of 30 rats of the Wistar breed were divided into 3 groups of 10 animals each. Group 1 underwent a sham procedure and was killed after 30 days; group 2 underwent bilateral oophorectomy and was killed after 30 days without receiving vitamin E supplementation and group 3 underwent bilateral oophorectomy and received vitamin E supplementation at a dose of 1,000 IU/kg once a week intra-muscularly for 30 days. Four weeks after the procedure, the rats were anesthetised and their bladders were rapidly removed, frozen and stored at -70 degrees C for Comet assaying, which was carried out on lymphocytes and vesicular urothelium cells. The 8-isoprostane concentration in plasma was also determined to confirm the presence of oxidative stress. The 8 isoprostane levels found were higher in oophorectomised rats that had not received vitamin E supplementation than in the sham group and the oophorectomised group with vitamin replacement. Tail moment analysis on the urothelial cells demonstrated that the oophorectomised group presented DNA damage that was statistically significant in comparison with the other groups. On the basis of the above data, vitamin E decreased the effects of oophorectomy on lipid peroxidation and avoided the DNA damage observed in urothelial cells. PMID- 17333438 TI - An unusual cause of postoperative detrusor overactivity. AB - Fallopian tube prolapse through a ruptured vagina is a rare, but well-documented, gynaecological condition. The majority of cases reported in the literature complicated vaginal hysterectomy and presented with vaginal bleeding and pelvic pain. We report a case after abdominal hysterectomy, which presented with urinary symptoms, an unreported presentation, and was managed successfully via the vaginal route. An update on the cases reported in the literature is also presented. PMID- 17333439 TI - Risk factors for the recurrence of pelvic organ prolapse after vaginal surgery: a review at 5 years after surgery. AB - The objective of this study was to determine the factors associated with the anatomic and functional recurrence of prolapse. An examination was performed in 134 of the 228 patients who underwent primary vaginal surgery for prolapse of the pelvic organs (POP) between 2000 and 2001. Anatomical recurrence of the prolapse was established by pelvic examination using the pelvic organ prolapse quantification (POPQ) staging system. Functional results were obtained by interview with the patients. Descriptive statistical analyses and multivariate logistic regression were performed to determine the factors associated with recurrence. Five years after surgery, 42 women (31.3%) presented anatomical recurrence of the prolapse (grade > or = II), and only 10 of the 134 (7.4%) had prolapse-related symptoms. Those with high body weight (>65 kg) and younger women (<60 years) were associated with an increase in the risk for both anatomical and functional recurrence. Advanced preoperative prolapse (grade III-IV) of any compartment was associated with anatomical failure but not with symptomatic recurrence. There was a poor correlation between anatomical and symptomatic recurrence. Younger women and those with a higher body weight are more likely to experience recurrent prolapse after vaginal repair. PMID- 17333440 TI - Marketed vaginal mesh kits: rampant experimentation or improved quality of care? Thoughts following the 2006 AUGS meeting by AUGS president Ingrid Nygaard, M.D. PMID- 17333441 TI - Mesh infection without erosion after ObTape sling insertion: a diagnostic challenge. AB - Infection is a recognised complication of using synthetic mesh tapes in continence surgery. It has only been reported alongside erosion after trans obturator sling insertion for urodynamic stress incontinence. A 41-year-old patient developed mesh infection. This infection was diagnosed 16 months after insertion, when it became an abscess and discharged through her groin. The condition was not suspected earlier, despite having examination under anesthesia and repeat cystoscopy. The patient recovered upon removing the mesh and remains continent. This case documents the possible development of mesh infection without erosion. It highlights the importance of taking this possibility into consideration when dealing with patients after continence surgery and explores how it can be detected. PMID- 17333442 TI - Prosthetic reinforcements: how to manage bladder injuries? AB - The aim of this study was to describe our experience in the management of bladder injuries occurring at intervesicovaginal dissection during the tension-free vaginal mesh (TVM) procedure. Seven hundred four patients were treated for prolapse by vaginal route using the TVM procedure. Bladder injury was diagnosed during the procedure in five patients. Polypropylene mesh was placed in the intervesicovaginal space after a careful repair of the bladder injury. Major postoperative complications were not diagnosed during the short-term follow up. We describe the occurrence and treatment of bladder injuries during the dissection phase in the TVM procedure. Such injuries can occur during the dissection. Placing an intervesicovaginal mesh is acceptable if cautious bladder repair is performed. PMID- 17333443 TI - Leiomyomas of the female urethra and bladder: a report of five cases and review of the literature. AB - Through the experience of five cases of leiomyoma developed in the female bladder and urethra with a review of the literature, we have made an effort to characterize the association of symptom with the size and location of the tumor and demonstrate an appropriate treatment. The study population was composed of patients who underwent surgery for bladder or urethral leiomyoma in our hospital from March 1990 to April 2005. Their medical records were reviewed retrospectively concerning the symptom, size and location of leiomyoma, the result of cystoscope and radiological examination, surgical method, pathologic report, complications, and recurrence. Four cases were diagnosed as urethral leiomyoma and one case as bladder leiomyoma. All patients with urethral leiomyoma were admitted for the chief complaint of a palpable tumor. When the tumor size was small, if it was located on the lateral side of the urethra, it was asymptomatic, but if located in the midline, it presented irritative or obstructive symptom. When it was big, if located on the lateral side, it presented irritative rather than obstructive symptom, and if located in the midline, it presented obstructive symptom. One case of bladder leiomyoma was discovered incidentally during ultrasonic exam. In all five cases, surgical removal was performed and complications or recurrence were not detected afterwards. Bladder and urethral leiomyomas are very rare and cause diverse manifestations from asymptomatic to irritative or obstructive symptom. It is presumed that the location and size of the tumor are associated with symptom. Unless it is the case with severe hemorrhage or obstructive acute renal failure, immediate surgery is not required. However, it is desirable to distinguish leiomyoma from malignant or other benign tumors by surgical biopsy or removal. PMID- 17333444 TI - Histological features of the rectovaginal septum in elderly women and a proposal for posterior vaginal defect repair. AB - To get support from morphological findings to develop a novel surgical procedure for posterior vaginal defect repair, we histologically examined the rectum-vagina interface tissues obtained from 20 elderly female cadavers. The rectovaginal septum (RVS) was defined here as an elastic fiber-rich plate (EFRP) along the posterior vaginal wall. It lined the posterior surface of the vein-rich zone of the vaginal wall and extended between the bilateral paracolpiums. The septum was more evident in the lower half of the interface than in the upper half. The RVS was often thin and interrupted. Since the RVS was not so clearly demonstrated in the upper vagina histologically, augmentation using some implant is considered to be necessary for the enterocele and high rectocele. Since the thickness and tightness of the RVS vary with the case in the lower vagina, surgical procedures for low rectocele repair should be individualized, including implant augmentation. PMID- 17333445 TI - Abscess formation at the ischiorectal fossa 7 months after the application of a synthetic transobturator sling for stress urinary incontinence in a type II diabetic woman. AB - A 50-year-old diabetic woman was referred to our unit because of high fever, foul smelling vaginal discharge and pain in the leg, 7 months after undergoing surgery for application of a transobturator suburethral sling. Patient evaluation revealed erosion of the tape through the vaginal wall; the infection had spread to the region of the internal obturator muscle and then up to the anterior recess of the ischiorectal fossa. The patient underwent surgery for sling removal, antibiotic therapy and, finally, surgical incisions to facilitate drainage of the abscess. All these passages were necessary to obtain complete resolution of the symptoms. Infectious complications are possible after transobturator sling procedures. Patients should then be informed about the risks of erosion and infection and be warned that the appearance of pain and foul-smelling vaginal discharge may indeed be the first symptom of subsequent and much more severe infectious complications. PMID- 17333446 TI - Beta-blocker use and risk of fractures in men and women from the general population: the MONICA/KORA Augsburg cohort study. AB - Use of beta-blockers is associated with a reduced risk of fractures in middle aged and older subjects from the general population. INTRODUCTION: The present prospective population-based study investigated the association between use of beta-blockers and incidence of any fracture. METHODS: The study was based on 1,793 persons 55 to 74 years of age who participated in one of the three MONICA Augsburg surveys between 1984 and 1995. Subjects were without any fracture at baseline. Incident fractures were assessed using a health questionnaire. Hazard ratios (HRs) were estimated from Cox proportional hazard models. RESULTS: During a mean follow-up of 10.7 years, there occurred 263 incident fractures. beta blocker users were older, were significantly more likely to be obese, to drink no alcohol, to have hypertension or diabetes, to use thiazides and statins, and to be physically inactive. The use of beta-blockers was associated with a lower risk of any fracture (HR 0.57; 95% CI = 0.36-0.90) after adjustment for age, sex and survey. Further adjustment for body mass index and education years only slightly attenuated the relationship (HR 0.60; 95% CI = 0.38-0.95) and additional adjustment for a variety of further risk factors did not attenuate the association (HR 0.60; 95% CI = 0.37-0.96). CONCLUSION: Use of beta-blockers was associated with a reduced risk of fractures in middle-aged and older subjects from the general population. PMID- 17333447 TI - Urban-rural differences in distal forearm fractures: Cohort Norway. AB - The prevalence of forearm fractures increased with increasing degree of urbanization for both genders in the population-based study "Cohort Norway" with more than 180,000 participants. The differences were not explained by available risk factors. Prospective studies with information on bone mineral density and falls are warranted. INTRODUCTION: The purpose was to investigate urban-rural gradients in self-reported forearm fractures and assess the contribution of possible explanatory factors. METHODS: "Cohort Norway" comprises ten population based surveys inviting 309,742 individuals age 20 years and older. All 181,891 participants underwent a standardized examination and answered 50 common questions, including one concerning former forearm fractures. Based on the home addresses, participants were divided into three population density groups: cities, densely populated areas and sparsely populated areas. Analyses were limited to 149,725 participants 30 years or over with valid information on exposure and outcome. Of these, 21,627 reported having suffered a forearm fracture. RESULTS: The prevalence of forearm fractures increased with increasing degree of urbanization for both genders. After adjustment for age and explanatory factors, the odds ratio of having sustained a forearm fracture in men living in densely populated areas and in cities were 1.12 (95% CI, 1.04-1.21) and 1.38 (95% CI, 1.30-1.46), respectively, compared to rural areas. Similar odds ratios were observed among women. CONCLUSIONS: Prospective studies are needed to verify whether lower bone mineral density, different lifestyle and/or more falls may explain the higher proportion of self-reported forearm fractures found in urban compared to rural areas. PMID- 17333448 TI - Modulation of soy isoflavones bioavailability and subsequent effects on bone health in ovariectomized rats: the case for equol. AB - INTRODUCTION: Soy products are of particular interest because of their potential health benefits in a range of hormonal conditions, such as osteoporosis, due to their high content in phytoestrogens. Because equol, the main metabolite from soy isoflavones, is thought to be powerful, the present study was designated to evaluate the bone-sparing effects of equol by either providing the molecule through the diet or by eliciting its endogenous production by modulating intestinal microflora by short-chain fructooligosaccharides (sc-FOS) or live microbial (Lactobacillus casei) together with daidzein, its precursor. METHODS: A comparison with daidzein and genistein was also performed. Rats (3 months old) were ovariectomised (OVX) or sham-operated (SH). Ovariectomised rats were randomly assigned to six experimental diets for 3 months: a control diet (OVX), the control diet supplemented with either genistein (G), or daidzein (D), or equol (E) at the level of 10 microg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 mug/g body weight/d, simultaneously with short chain FOS (Actilight, Beghin-Meiji) (D+FOS) or Lactobacillus casei (Actimel, Danone) (D+L). The SH rats were given the same control diet as OVX. RESULTS: Genistein, daidzein or equol exhibited a bone sparing effect. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared to that of OVX rats), as was the metaphyseal compartment. Bone strength was improved by E consumption, but not by genistein or daidzein given alone. As far as the FOS diet is concerned, the addition of prebiotics significantly raised efficiency of the daidzein protective effect on both femoral BMD and mechanical properties. The effects of lactobacillus were similar, except that the increase in metaphyseal BMD was not significant. CONCLUSION: In conclusion, long-term equol consumption, like genistein and daidzein, in the ovariectomized rat, provides bone sparing effects. Adding indigestible sugars, such as FOS or live microbial as L. casei, in the diet significantly improves daidzein protective effects on the skeleton. PMID- 17333449 TI - Cost-effectiveness of alendronate in the treatment of postmenopausal women in 9 European countries--an economic evaluation based on the fracture intervention trial. AB - Treatment with alendronate (Fosamax) has been shown to significantly reduce the risk of fragility fractures. Cost-effectiveness of treatment was assessed in nine European countries in a Markov model and was generally found to be cost effective in women with a previous spine fracture. INTRODUCTION: Treatment with alendronate (Fosamax) reduces the risk of osteoporotic fractures at the spine, hip and wrist in women with and without prevalent vertebral fracture. Cost-effectiveness estimates in one country may not be applicable elsewhere due to differences in fracture risks, costs and drug prices. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women with alendronate in nine European countries, comprising Belgium, Denmark, France, Germany, Italy, Norway, Spain, Sweden, and the UK. METHODS: A Markov model was populated with data for the nine European populations. Effect of treatment was taken from the Fracture Intervention Trial, which recruited women with low BMD alone or with a prior vertebral fracture. RESULTS: The cost per QALY gained of treating postmenopausal women with prior vertebral fractures ranged in the base case from "cost saving" in the Scandinavian countries to 15,000 in Italy. Corresponding estimates for women without prior vertebral fractures ranged from "cost saving" to 40,000. CONCLUSIONS: In relation to thresholds generally used, the analysis suggests that alendronate is very cost effective in the treatment of women with previous vertebral fracture, and in women without previous vertebral fracture, cost-effectiveness depends on the country setting, discount rates, and chosen monetary thresholds. PMID- 17333450 TI - A program with a dedicated coordinator improved chart documentation of osteoporosis after fragility fracture. AB - Post-fracture osteoporosis care is becoming recognized as essential by the orthopaedic community, but programs and systems are needed to ensure that this care is routinely provided. Chart documentation related to OP, which is valuable for continuity of care, increased significantly following establishment of an osteoporosis program with a dedicated coordinator. INTRODUCTION: Post-fracture osteoporosis (OP) care has been repeatedly reported to be inadequate. Through a coordinator-based program, we addressed OP care for more than 95% of fragility fracture patients (1), but we do not know if documentation by orthopaedic surgeons improved. The literature suggests that chart documentation, though underestimating true care, is an indicator of the salient aspects of a condition. Thus chart documentation could be used to reflect an emerging recognition of OP as an important issue to be addressed in the orthopaedic management of the fragility fracture. The purpose of this study was to evaluate if there was an increased documentation of OP by orthopaedic surgeons before and after introduction of a coordinator-based program where the coordinator was known to address OP in 95% of cases. METHODS: Chart audits were conducted to quantify OP documentation for patients treated after program initiation compared with age-, sex-, and fracture type-matched controls who presented prior to program implementation. Documentation rates were compared using chi(2) tests. Multivariable logistic regression analyses were performed to identify patient characteristics associated with OP-related documentation. RESULTS: After program implementation, chart documentation of OP diagnosis (unadjusted OR 2.2, 95% CI 1.1-4.4), of referral for OP follow-up (unadjusted OR 3.1, 95% CI 1.5-6.1), and of initiation of OP management (unadjusted OR 8.2, 95% CI 4.0-16.5) by orthopaedic surgeons was more likely. Being in the post-implementation group was stronger than any patient factors in predicting OP charting. CONCLUSIONS: Physicians working in a clinic with a coordinator-based OP program were more likely to document OP-related care in patients' medical charts. We believe this in turn reflected increased attention to OP by physicians in the orthopaedic management of fragility fractures. PMID- 17333451 TI - Hetereogeneity in skeletal response to full-length parathyroid hormone in the treatment of osteoporosis. AB - In the PaTH trial, among the 119 women randomized to parathyroid hormone PTH(1 84) and 60 to alendronate, we found much greater variation in BMD and markers in response to PTH(1-84) compared to alendronate. No baseline participant characteristic consistently predicted increased bone density response to PTH(1 84), although women with larger changes in 1,25 dihydroxyvitamin D during therapy had larger increases in BMD. INTRODUCTION: We examined variability in BMD and markers of bone turnover in response to treatment with PTH(1-84) or alendronate in the PaTH trial. METHODS: Differences in SD were examined using Levine's test for homogeneity of variance. Change in BMD across quartiles of participant characteristics was examined using ANOVA. RESULTS: We found much greater variation in response to PTH(1-84) compared to alendronate. The SD for change in cancellous spine BMD (by QCT) was 32% on PTH(1-84) compared to 13% on alendronate (p < 0.0001). The higher variability in the PTH(1-84) group was due to substantial numbers of women with large increases in BMD on PTH(1-84). Similarly, the SD of changes in markers of formation and resorption were significantly higher on PTH(1-84) than on ALN. No baseline participant characteristics predicted increased bone density response to PTH(1-84) therapy. However, change in 1,25-OH(2)D explained 16% of the variance in BMD response to PTH(1-84). CONCLUSION: There is significant variability in the skeletal response to PTH(1 84), which exceeds that observed with alendronate. Changes in 1,25-OH(2)D were related to larger gains in BMD. This finding may have implications for elucidating either the pathway by which PTH affects the skeleton or traits that result in particular responsiveness to PTH therapy. PMID- 17333452 TI - Psychometric properties of the "Osteoporosis and You" questionnaire: osteoporosis knowledge deficits among older community-dwelling women. AB - In older women, knowledge about risk factors for osteoporosis was good, with over 75% responding correctly to questions about lifestyle factors, family history, height loss, and menopausal status. However, significant knowledge deficits were identified regarding osteoporosis "consequences" and "prevention and treatment." INTRODUCTION: We examined osteoporosis knowledge by testing the psychometric properties of the 10-item knowledge component of the "Osteoporosis and You" questionnaire. Several knowledge domains were hypothesized. METHODS: Community dwelling women aged 65-90 years residing within two regions of Ontario, Canada were studied (N = 869). Data were collected by standardized telephone interviews in 2003 and 2004. Items to which 75% or more responded correctly were identified as having a low index of difficulty; the remaining items identified areas of knowledge deficit. Confirmatory factor analysis was used to test scale structure. RESULTS: Six of the ten items had a low index of difficulty. These items largely examined osteoporosis risk factors. The remaining four items identified significant knowledge deficits in the areas of osteoporosis consequences, prevention, and treatment. Confirmatory factor analysis identified four distinct osteoporosis knowledge domains. However, the internal consistency was low for all but one domain, which examined "prevention and treatment." CONCLUSION: Although older women appear to be aware of osteoporosis risk factors, knowledge deficits regarding the consequences of osteoporosis and that treatment exists to prevent bone loss were identified. Better understanding of the multi-dimensional aspects of osteoporosis knowledge may help to inform the development of effective educational interventions. PMID- 17333453 TI - ECCEO 7. Abstracts of the 7th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. March 28-31, 2007. Porto, Portugal. PMID- 17333456 TI - A reasonable mechanism for visible light-induced skin rejuvenation. AB - In recent years, much research has been done in the field of non-ablative skin rejuvenation. This comes as a response to the continuous demand for a simple method of treating rhytides, UV exposure, and acne scars. Numerous researches involve visible light-pulsed systems (20-30 J/cm(2)). The mechanism of action is believed to be a selective heat-induced denaturalization of dermal collagen that leads to subsequent reactive synthesis (Bitter Jr., Dermatol. Surg., 26:836-843, 2000; Fitzpatrick et al., Arch. Dermatol., 132:395-402, 1996; Kauvar and Geronemus, Dermatol. Clin., 15:459-467, 1997; Negishi et al., Lasers Surg. Med., 30:298-305, 2002; Goldberg and Cutler, Lasers Surg. Med., 26:196-200, 2000; Hernandez-Perez and Ibeitt, Dermatol. Surg., 28:651-655, 2002). In this study, we suggest a different mechanism for photorejuvenation based on light-induced reactive oxygen species (ROS) formation. We irradiated collagen in vitro with a broadband of visible light (400-800 nm, 24-72 J/cm(2)) and used the spin trapping coupled with electron paramagnetic resonance spectroscopy to detect ROS. Irradiated collagen resulted in hydroxyl radicals formation. We propose, as a new concept, that visible light at the energy doses used for skin rejuvenation (20-30 J/cm(2)) produces high amounts of ROS, which destroy old collagen fibers, encouraging the formation of new ones. On the other hand, at inner depths of the skin, where the light intensity is much weaker, low amounts of ROS are formed, which are well known to stimulate fibroblast proliferation. PMID- 17333457 TI - Adaptation of a photochemical method to initiate recurrent platelet-mediated thrombosis in small animals. AB - Platelet-mediated thrombosis represents the initial precipitating event in the genesis of unstable angina, acute myocardial infarction, and stroke. As a result, there is considerable interest in the preclinical discovery and screening of new 'anti-platelet' therapies aimed at limiting the incidence and reoccurrence of arterial thrombosis-efforts that, to date, have largely required the use of large animal models of thrombotic occlusion. In the current report, we describe the successful development of a small-animal (rat) model of spontaneous and recurrent platelet-mediated arterial thrombosis achieved by the in vivo administration of a photoactive dye (rose bengal) followed by focal illumination with green laser light. PMID- 17333458 TI - Influence of autoclaved saprotrophic fungal mycelia on proteolytic activity in ectomycorrhizal fungi. AB - The production of proteolytic enzymes by several strains of ectomycorrhizal fungi i.e., Amanita muscaria (16-3), Laccaria laccata (9-12), L. laccata (9-1), Suillus bovinus (15-4), Suillus bovinus (15-3), Suillus luteus (14-7) on mycelia of Trichoderma harzianum, Trichoderma virens and Mucor hiemalis and sodium caseinate, yeast extract was evaluated. The strains of A. muscaria (16-3) and L. laccata (9-12) were characterized by the highest activity of the acidic and neutral proteases. Taking the mycelia of saprotrophic fungi into consideration, the mycelium of M. hiemalis was the best inductor for proteolytic activity. The examined ectomycorrhizal fungi exhibited higher activity of acidic proteases than neutral ones on the mycelia of saprotrophic fungi, which may imply the participation of acidic proteases in nutrition. PMID- 17333459 TI - The trophic structure of bark-living oribatid mite communities analysed with stable isotopes ((15)N, (13)C) indicates strong niche differentiation. AB - The aim of the present study was to identify food sources of bark-living oribatid mites to investigate if trophic niche differentiation contributes to the diversity of bark living Oribatida. We measured the natural variation in stable isotope ratios ((15)N/(14)N, (13)C/(12)C) in oribatid mites from the bark of oak (Quercus robur), beech (Fagus sylvatica), spruce (Picea abies) and pine (Pinus sylvestris) trees and their potential food sources, i.e., the covering vegetation of the bark (bryophytes, lichens, algae, fungi). As a baseline for calibration the stable isotope signatures of the bark of the four tree species were measured and set to zero. Oribatid mite stable isotope ratios spanned over a range of about 13 delta units for (15)N and about 7 delta units for (13)C suggesting that they span over about three trophic levels. Different stable isotope signatures indicate that bark living oribatid mites feed on different food sources, i.e., occupy distinct trophic niches. After calibration stable isotope signatures of respective oribatid mite species of the four tree species were similar indicating close association of oribatid mites with the corticolous cover as food source. Overall, the results support the hypothesis that trophic niche differentiation of bark living oribatid mites contributes to the high diversity of the group. PMID- 17333461 TI - Effects of relative humidity on development, fecundity and survival of three storage mites. AB - The developmental rate of immature stages and the reproduction of adults of Tyrophagus putrescentiae (Schrank), T. neiswanderi Johnston and Bruce and Acarus farris (Oudemans) were examined at 70, 80 and 90% r.h. and a constant temperature of 25 degrees C. At 70% r.h., T. putrescentiae and A. farris immature stages failed to reach the protonymph stage as 100% of the larvae died, whereas T. neiswanderi was able to complete development. The developmental time of all immature stages for the three species was significantly increased as relative humidity was reduced. The mobile stages were particularly susceptible, as the time needed to complete their development at lower relative humidities suffered greater increases than the egg stage. At 70% r.h., T. putrescentiae and A. farris were not able to lay eggs and only 24% of T. neiswanderi pairs were fertile. The reproductive parameters of the three species at the relative humidities at which they were able to lay eggs showed significant differences, except for the percentage of fertile mating at 80 and 90% r.h. As relative humidity increased, preoviposition period was reduced and fecundity and daily fecundity was increased, whereas the oviposition period showed different patterns for the three species. The intrinsic rate of increase (r ( m )) of T. neiswanderi at 70% r.h. was negative indicating that, at these conditions, mite populations of this species will diminish until they disappear. As relative humidity increased from 80 to 90% r.h. this parameter was almost twofold for both Tyrophagus species. The r ( m ) obtained for A. farris at 90% r.h. was similar to that of T. neiswanderi at the same humidity while at 80% r.h. it was very small so that the population doubling time was more than 84 days. The influence of relative humidity on biology of these mites and its practical application as control measure are discussed. PMID- 17333460 TI - Living at the threshold: where does the neotropical phytoseiid mite Typhlodromalus aripo survive the dry season? AB - The establishment of the neotropical predatory mite Typhlodromalus aripo in sub Saharan Africa has resulted in broadly successful biological control of the cassava green mite Mononychellus tanajoa throughout the cassava belt of Africa. In some mid-altitude areas and drier lowland savannahs of sub-Saharan Africa, which are characterized by cool or hot long (> or =5 months) dry seasons, the predator disappears from its habitat in the cassava apex during the dry season and reappears after the onset of rains. It is not known, however, where the predator remains during this time period. In this study, we conducted a field enclosure experiment of cassava plants with the objectives to determine if (a) T. aripo survives at very low densities in the apex, if (b) it survives in the soil or leaf litter below the cassava plant, and if (c) it recolonizes the cassava plant from the surrounding vegetation. Towards the end of the dry season, when the predators had disappeared from all cassava plants included in the experiment, five treatments were applied: (1) plants without enclosure; (2) plants with enclosure; (3) plants with enclosure, apices removed; (4) plants with enclosure, glue barrier around stem; and (5) plants kept free of T. aripo, without enclosure. Predator (re)appearance on cassava apices was monitored non destructively at weekly intervals and was expressed as the proportion of plants with at least one apex with T. aripo per total number of plants of the treatment. The predators reappeared first on the plants of the treatments (1), (2), and (4). With a time lag of 7-8 weeks, the predators appeared also on the plants of the treatments (3) and (5). The time pattern of the predator's (re)appearance in the cassava apex of the different treatments suggests that (a) T. aripo survives the dry season in very low densities in the cassava apex; this result is supported by an assessment of the efficiency of non-destructive visual in-field apex inspections which proved that about 10% of the cassava apices that had T. aripo were not recognized as such; (b) T. aripo does not survive in the soil or leaf litter, but we did document cases in a screenhouse experiment, where few individuals migrated down to the ground and walked over exposed soil until they reached the apex bouquet traps; additionally, microclimate measurements in various cassava plant strata proved that the cassava apex and the cassava stem base are the locations with the highest relative humidity during the dry season- which makes the stem base a potentially interesting refuge; (c) T. aripo does not survive in the surrounding vegetation, which is supported by a vegetation survey, where T. aripo was not found on any other plant species than cassava. PMID- 17333462 TI - Estimating the intrinsic rate of increase of Tetranychus urticae: which is the minimum number of immature individuals to consider? AB - The relationship between the number of immature individuals of Tetranychus urticae used to calculate life table parameters (sex ratio, development time, immature survival and the intrinsic rate of increase) and the accuracy of such determinations has been estimated. Additionally, the approach used in this paper, which considers each female offspring as a separate replicate, has allowed statistical comparison of the parameters obtained. At least the first four eggs from 16 females should be followed up to completion of their development to prevent the occurrence significant differences for the selected parameters. However, our results indicate that optimal sample sizes are different for the different life table parameters considered and should adapt to the preset level of accuracy. PMID- 17333463 TI - Construction of the bifunctional enzyme cellulase-beta-glucosidase from the hyperthermophilic bacterium Thermotoga maritima. AB - An artificial bifunctional enzyme, cellulase-beta-glucosidase, was prepared by gene fusion from the hyperthermophilic bacterium Thermotoga maritima MSB8. The fusion protein exhibited both cellulase (Cel5C) and beta-glucosidase (BglB) activity when the bglB gene was fused to downstream of cel5C, but not when cel5C was fused to downstream of bglB. The specific activity of the bifunctional enzyme was 70% lower than that of cellulase or beta-glucosidase. The fusion enzyme was purified, and the MW was estimated as 114 kDa. The fusion enzyme displayed optimum cellulase activity at pH 8.0 and 70 degrees C over 30 min, and optimal beta-glucosidase activity at pH 7.0 and 80 degrees C over 30 min. PMID- 17333464 TI - Expression, purification, and characterization of recombinant Chinese shrimp crustin-like protein (CruFc) in Pichia pastoris. AB - A crustin-like protein (CruFc) from Fenneropenaeus chinensis was expressed in Pichia pastoris and then purified to electrophoretic homogeneity on a Sephacryl S 100 column with a band corresponding to the expected one (13 kDa) shown by 15% SDS-PAGE. Western blot indicated that the rCruFc specifically reacted with polyclonal rabbit anti-Fenneropenaeus chinensis CruFc. Production in a 5 l bioreactor gave 237 mg rCruFc/l. Antimicrobial assay revealed that 4 microM rCruFc inhibited growth of Staphylococcus aureus. PMID- 17333465 TI - Mineralization of diuron [3-(3,4-dichlorophenyl)-1, 1-dimethylurea] by co immobilized Arthrobacter sp. and Delftia acidovorans. AB - Mineralization of diuron has not been previously demonstrated despite the availability of some bacteria to degrade diuron into 3,4-dichloroaniline (3,4 DCA) and others that can mineralize 3,4-DCA. A bacterial co-culture of Arthrobacter sp. N4 and Delftia acidovorans W34, which respectively degraded diuron (20 mg l(-1)) to 3,4-DCA and mineralized 3,4-DCA, were able to mineralize diuron. Total diuron mineralization (20 mg l(-1)) was achieved with free cells in co-culture. When the bacteria were immobilized (either one bacteria or both), the degradation rate was higher. Best results were obtained with free Arthrobacter sp. N4 cells co-cultivated with immobilized cells of D. acidovorans W34 (mineralization of diuron in 96 h, i.e., 0.21 mg l(-1 )h(-1) vs. 0.06 mg l(-1 )h( 1) with free cells in co-culture). PMID- 17333466 TI - Agarose-gelatin conjugate for adherent cell-enclosing capsules. AB - Spherical capsules were prepared by extruding aqueous agarose-gelation conjugate solution into co-flowing liquid paraffin at 38 degrees C and cooling the resultant emulsion. Capsule diameter was controlled between 40 and 250 mum by changing the velocity of the liquid paraffin. Adherent Crandall-Reese feline kidney cells enclosed in conjugate capsules of 141 +/- 23 mum diam. had a higher degree of proliferation than those in unmodified agarose capsules. Mitochondrial activity, detected for cell-enclosing conjugate capsules normalized against unit volume of gel, was about double that of unmodified agarose capsules over 28 days. These results demonstrated the feasibility of agarose-gelatin conjugate as a material of cell-enclosing capsules. PMID- 17333467 TI - Beneficial effects of Bacillus licheniformis on the intestinal microflora and immunity of the white shrimp, Litopenaeus vannamei. AB - When Bacillus licheniformis was administered to the white shrimp, Litopenaeus vannamei, although the total bacterial counts in the intestinal tract of the shrimp remained constant, Vibrio numbers significantly decreased (P < 0.05). Haemocyte counts together with phenoloxidase and superoxide dismutase activities of the shrimp were significantly higher (P < 0.05) in treatments than in the control. Thus, administration of B. licheniformis can improve the white shrimp's intestinal microflora and its immune ability. PMID- 17333468 TI - Biotransformation of phenylpyruvic acid to phenyllactic acid by growing and resting cells of a Lactobacillus sp. AB - Phenyllactic acid (PLA) is a novel antimicrobial compound derived from phenylalanine (Phe). Lactobacillus sp. SK007, having high PLA-producing ability, was isolated from Chinese traditional pickles. When 6.1 mM phenylpyruvic acid (PPA) was used to replace Phe as substrate at the same concentration, PLA production increased 14-fold and the fermentation time decreased from 72 h to 24 h with growing cells. With resting cells, however, 6.8 mM PLA could be obtained as optimal yield using the following conditions: 12 mM PPA, 55 mM glucose, pH 7.5, 35 degrees C and 4 h. PMID- 17333470 TI - Can we learn more about the etiology of cardiovascular disease? PMID- 17333469 TI - Effect of cadmium alone and in combination with butachlor on soil enzymes. AB - The ecological toxicity of cadmium (Cd, 10 mg kg(-1 )of dry weight soil) and butachlor (10, 50 and100 mg kg(-1 )of dry weight soil) in both their single and combined effects on soil urease and phosphatase was studied after 1, 3, 7, 14, 21 and 28 days exposure under controlled conditions in paddy and phaeozem soils. The results showed that Cd reduced the activities of urease and phosphatase at early incubation time (1-7 days), while the reduction almost disappeared at the end of the incubation. The effect of Cd on phosphatase was more pronounced than that on urease. The activities of urease and phosphatase were reduced by butachlor, while urease activity was significantly (P < 0.05 or P < 0.01) improved when the concentrations of butachlor were 10 and 50 mg kg(-1) at the end of the incubation. When Cd (10 mg kg(-1)) was combined with butachlor (50 and 100 mg kg( 1)), the activities of urease and phosphatase became lower than without combination at early incubation time, which indicated that the toxicity of Cd significantly increased (P < 0.05 or P < 0.01). However, when Cd (10 mg kg(-1)) was combined with butachlor (10 mg kg(-1)), the activities of urease and phosphatase became higher than those without combination at the end of the incubation, which indicated that the toxicity of Cd decreased. It was indicated that the combined effects depended largely on the incubation time and the concentration ratio of Cd and butachlor. In addition, it was showed that the combined effects of butachlor and Cd appeared different in paddy from phaeozem, which may be related to the different properties of these soils. PMID- 17333471 TI - Reproducibility of the past year and historical self-administered total physical activity questionnaire among older women. AB - Few studies have evaluated the reliability of a self-administered current and historical physical activity questionnaire (PAQ) among middle-aged and elderly women. We evaluated the reliability of a self-administered PAQ designed to assess total (24 h) current and historical physical activity at age 15, 30, and 50 years, which was completed by a subgroup of 303 women aged 56-75 years from the Swedish Mammography Cohort (SMC). Total physical activity covered occupational and household activity as well as walking/bicycling, exercise, and inactivity (sitting watching TV/reading). Reliabilities (1-year test-retest) of continuous activity measures in metabolic equivalents were evaluated using an intraclass correlation coefficient (ICC); classification consistency was evaluated using sensitivity and specificity statistics. The ICC for total current physical activity was 0.69; for specific types of activities the ICC ranged from 0.49 to 0.59; for historical physical activity, the reliabilities for total activity ranged from 0.75 for age 50 to 0.81 for age 30 years, being substantial for occupational activities (ICC = 0.73-0.75), and fair to moderate for inactivity (ICC = 0.31-0.60). These data indicate that the PAQ used in the SMC is a satisfactory and reproducible measure of current and historical physical activity, for total as well as for different types of activities. PMID- 17333473 TI - Oasis land-use change and its environmental impact in Jinta Oasis, arid northwestern China. AB - Land use change resulted in land degradation is a focus of research on global environmental changes and plays a significant role in the stability and economic development of oases in arid regions of China. Jinta Oasis, a typical oasis of temperate arid zone in northwestern China, was investigated to assess land-use change dynamics during 1988-2003 with the aid of satellite remote sensing and GIS, and to explore the interaction between these changes and oasis environment. Six land-use types were identified, namely: cropland, forestland, grassland, water, urban or built-up land, and barren land. The results indicate that cropland, urban/built-up land, and barren land increase greatly by 30.03, 13.35, and 15.52 km(2), respectively; but grassland and forestland areas decrease rapidly by 58.06, and 1.76 km(2), respectively. These results also show that obvious widespread changes in land-use occur within the whole oasis over the study period and result in severe problems of environmental degradation (i.e. land desertification, decline of groundwater, and vegetation degeneracy). PMID- 17333472 TI - Associations between overall physical activity level and cardiovascular risk factors in an adult population. AB - BACKGROUND: It is well established that physical activity level is inversely associated with cardiovascular morbidity and mortality, and with all-cause mortality. However, the dose-response relationship between physical activity and other cardiovascular disease risk factors is not fully understood. The aim of the present study was to explore the dose-response relationship between daily physical activity, as measured by a metabolic equivalent score, and BMI, waist circumference, waist hip ratio, total cholesterol, HDL, LDL, triglycerides, systolic and diastolic blood pressure. METHODS: A total of 1693 men and women, 33 64 years of age, from the 3 year follow-up of a population-based intervention study, were included in this cross-sectional study. Information on physical activity and other lifestyle factors was obtained by self-report questionnaire. Associations between activity level and biological variables were explored by general linear regression. RESULTS: Data from 835 (51%) men and 805 (49%) women were included. Mean age was 50.8 years (33-64). A significant inverse association between average 24-hour physical activity level < or =45 METs and waist circumference (men p = 0.012, women p = 0.011), BMI (p = 0.0004), waist-hip-ratio (p = 0.002) and triglycerides (p = 0.0001) was found as well as a positive association with HDL (p = <0.0001). In those with an activity level above 45 METs there were no associations. No association was found with total cholesterol, LDL, systolic or diastolic blood pressure. CONCLUSION: This study suggests a linear dose-response relationship between activity level and certain biological cardiovascular risk factors up to a threshold of a daily 24 h MET-score of 45, which corresponds to a moderate physical activity level. PMID- 17333474 TI - Effect of on-site sanitation on groundwater contamination in basaltic environment -a case study from India. AB - On-site sanitation is increasingly adopted in urban cities in India. The adoption of on-site sanitation system puts the groundwater resources in the vicinity of the system at a greater risk. Microbial contaminants as well as chemical contaminants like Chloride and Nitrate are generated from human waste. These contaminants travel through the medium and ultimately get in contact with the groundwater. Hence, the groundwater sources are vulnerable to nitrate contamination near the on-site sanitation systems. The present study indicates significant Nitrate and Chloride contamination in samples collected close to on site sanitation systems. The recommended limit set by the Bureau of Indian standards (BIS) limit of 45 mg/l for Nitrate concentration is also exceeded in few samples. The study indicates that Bacterial as well as Nitrate contamination is more in Monsoon as compared to Summer. PMID- 17333475 TI - Fish scales as bio-indicator of water quality of River Ganga. AB - Various studies have been conducted in the past on the fresh waters related to the various aspects of limnology, physico-chemistry, primary productivity, plankton etc. in relation to environmental conditions and ecology, flora and fauna of River Ganga. In the present investigation some recent approach have been made to study the various parts of fishes like gill structures, scales for age determination, length and weight of fish for growth assessments etc. The SEM study of scales in relation to pollution and environmental conditions is a recent approach. At this stage, in the present study the scales of two most common fishes found in the study stretch were involved to create a base line. PMID- 17333476 TI - Disseminating risk information to familial adenomatous polyposis families. AB - The Hereditary Cancer Registers (HCR) offer registration to individuals at risk of hereditary bowel cancer. Most families are registered to the HCR via Familial Cancer Clinics (FCC)s. The FCCs work together with the HCR to inform family members that they may be at increased risk of hereditary bowel cancer. In 2002, The Hunter Family Cancer Service (HFCS) and the HCR developed a system to ensure at risk family members become informed of their risk. Evaluation of this system is presented. The system involves tracking which family members are informed of their risk using a rating system. Being informed is graded numerically, from 5 (not informed) through to 1(definitely informed). Changes in score are brought about through staff and the FCC and HCR working with registrants to contact at risk family members. This study analyses data collected for a subgroup of 21 families registered with the HCR by the HFCS. Baseline and resulting scores indicated whether the 738 at risk family members had become better informed of their risk. One hundred and sixty eight individuals changed to a score of "definitely informed" and 230 individuals score changed from "not informed" to being better informed. The results demonstrate significant change in these family members towards becoming better informed (z = -13.88, P < 0.0001, Wilcoxon signed ranks test). These data suggest that the system for informing family members of their risk has resulted in significant positive change towards these individuals becoming more informed. The system has the potential to reach over 2,800 at risk family members, of registered families, resulting in improved surveillance and better health outcomes. PMID- 17333478 TI - Molecular analyses of mitochondrial pseudogenes within the nuclear genome of arvicoline rodents. AB - Nuclear sequences of mitochondrial origin (numts) are common among animals and plants. The mechanism(s) by which numts transfer from the mitochondrion to the nucleus is uncertain, but their insertions may be mediated in part by chromosomal repair mechanisms. If so, then lineages where chromosomal rearrangements are common should be good models for the study of numt evolution. Arvicoline rodents are known for their karyotypic plasticity and numt pseudogenes have been discovered in this group. Here, we characterize a 4 kb numt pseudogene in the arvicoline vole Microtus rossiaemeridionalis. This sequence is among the largest numts described for a mammal lacking a completely sequenced genome. It encompasses three protein-coding and six tRNA pseudogenes that span approximately 25% of the entire mammalian mitochondrial genome. It is bordered by a dinucleotide microsatellite repeat and contains four transposable elements within its sequence and flanking regions. To determine the phylogenetic distribution of this numt among the arvicolines, we characterized one of the mitochondrial pseudogenes (cytochrome b) in 21 additional arvicoline species. Average rates of nucleotide substitution in this arvicoline pseudogene are estimated as 2.3 x 10( 8) substitutions/per site/per year. Furthermore, we performed comparative analyses among all species to estimate the age of this mitochondrial transfer at nearly 4 MYA, predating the origin of most arvicolines. PMID- 17333477 TI - Founder mutations in early-onset, familial and bilateral breast cancer patients from Russia. AB - Previous studies indicate that founder mutations may play a noticeable role in breast cancer (BC) predisposition in Russia. Here we performed a systematic analysis of eight recurrent mutations in 302 BC cases (St.-Petersburg, Russia), which were selected due to the presence of clinical indicators of hereditary disease (bilaterality and/or early onset (< or =40 years) and/or family history). BC-associated alleles were revealed in 46 (15.2%) women. BRCA1 5382insC mutation was detected in 29 (9.6%) patients, CHEK2 1100delC in 9 (3.0%), BRCA1 4153delA in 3 (1.0%), CHEK2 IVS2+1G>A in 2 (0.7%), and BRCA1 185delAG, BRCA2 6174delT and NBS1 657del5 in 1 (0.3%) patient each. No cases with BRCA1 300T>G (C61G) mutation was identified. The obtained data suggest that a significant fraction of hereditary BC cases in Russia can be diagnosed using only a limited number of simple PCR tests. PMID- 17333479 TI - Landscape conservation genetics of Dipteryx alata ("baru" tree: Fabaceae) from Cerrado region of central Brazil. AB - In this paper random amplified polymorphic DNA (RAPD) was used to evaluate the degree of among-population differentiation and associated spatial patterns of genetic divergence for Dipteryx alata Vogel populations from Cerrado region of central Brazil, furnishing support for future programs of conservation of this species. We analyzed patterns of genetic and spatial population structure using 45 RAPD loci scored for 309 trees, sampled from five different regions with two populations each. Genetic structure analysis suggested that panmixia null hypothesis can be rejected, with significant among-population components of 15%. Hierarchical partition by Analysis of Molecular Variance (AMOVA) shows that 5% of genetic variation is within regions, whereas 10% of variation is among regions, and these results were confirmed by a Bayesian analyses on HICKORY. The Mantel correlogram revealed that this divergence is spatially structured, so that local populations situated at short geographic distances could not be considered independent units for conservation and management. However, genetic discontinuities among populations were found in the northwest and southeast parts of the study area, corresponding to regions of recent socio-economic expansion and high population density, respectively. Taking both geographic distances and genetic discontinuities into account it is possible to establish a group of population to be conserved, covering most of D. alata geographic distribution and congruent with previously established priority areas for conservation in the Cerrado region. PMID- 17333480 TI - Diffuse unilateral subacute neuroretinitis: report of a case from the Indian subcontinent and the importance of immediate photocoagulation. AB - PURPOSE: To report a case of DUSN from the Indian subcontinent and emphasize the importance of immediate photocoagulation. METHOD: Review of case record. RESULT: The referring ophthalmologist had photographed the subretinal worm but had not undertaken laser photocoagulation. On presentation to us the patient had features typical of DUSN but no worm could be detected despite repeated examinations. Failure to localize the worm at subsequent examinations resulted in only partial recovery of vision. CONCLUSION: Whenever the nematode is detected, immediate laser photocoagulation of the worm is necessary as the migratory worm may be difficult to identify later on. This is necessary to prevent the otherwise natural decline in vision. PMID- 17333481 TI - kScore: a novel machine learning approach that is not dependent on the data structure of the training set. AB - Currently machine learning approaches used in Quantitative Structure Activity Relationship (QSAR) model generation impose restrictions and/or make assumptions on how the training set descriptors correlate with a target activity. kScore has been developed as the first machine learning approach that does not require the training data to conform to a defined kernel, accommodates uneven data point distributions in the descriptor space, and optimizes the weight of each dimension in the descriptor space in order to identify the descriptors most relevant to the target property. The ability of kScore to adapt to virtually any correlation makes it essential that generalization terms be included to inhibit overtraining. The Structural Risk Minimization principle and the linear epsilon-insensitive loss terms have been added to the kScore optimization function. The resulting kScore algorithm has proven to be quite universal across several datasets and either produces results similar to or outperforms the most predictive machine learning algorithms tested, such as SVM, kNN, Recursive Partitioning, Neural Networks, Gaussian Process, and the Bayesian Classifier. PMID- 17333482 TI - Lead-like, drug-like or "Pub-like": how different are they? AB - Academic and industrial research continues to be focused on discovering new classes of compounds based on HTS. Post-HTS analyses need to prioritize compounds that are progressed to chemical probe or lead status. We report trends in probe, lead and drug discovery by examining the following categories of compounds: 385 leads and the 541 drugs that emerged from them; "active" (152) and "inactive" (1488) compounds from the Molecular Libraries Initiative Small Molecule Repository (MLSMR) tested by HTS; "active" (46) and "inactive" (72) compounds from Nature Chemical Biology (NCB) tested by HTS; compounds in the drug development phase (I, II, III and launched), as indexed in MDDR; and medicinal chemistry compounds from WOMBAT, separated into high-activity (5,784 compounds with nanomolar activity or better) and low-activity (30,690 with micromolar activity or less). We examined Molecular weight (MW), molecular complexity, flexibility, the number of hydrogen bond donors and acceptors, LogP-the octanol/water partition coefficient estimated by ClogP and ALOGPS), LogSw (intrinsic water solubility, estimated by ALOGPS) and the number of Rule of five (Ro5) criteria violations. Based on the 50% and 90% distribution moments of the above properties, there were no significant difference between leads of known drugs and "actives" from MLSMR or NCB (chemical probes). "Inactives" from NCB and MLSMR were also found to exhibit similar properties. From these combined sets, we conclude that "Actives" (569 compounds) are less complex, less flexible, and more soluble than drugs (1,651 drugs), and significantly smaller, less complex, less hydrophobic and more soluble than the 5,784 high-activity WOMBAT compounds. These trends indicate that chemical probes are similar to leads with respect to some properties, e.g., complexity, solubility, and hydrophobicity. PMID- 17333483 TI - Improved estimation of ligand-macromolecule binding affinities by linear response approach using a combination of multi-mode MD simulation and QM/MM methods. AB - Structure-based predictions of binding affinities of ligands binding to proteins by coordination bonds with transition metals, covalent bonds, and bonds involving charge re-distributions are hindered by the absence of proper force fields. This shortcoming affects all methods which use force-field-based molecular simulation data on complex formation for affinity predictions. One of the most frequently used methods in this category is the Linear Response (LR) approach of Aquist, correlating binding affinities with van der Waals and electrostatic energies, as extended by Jorgensen's inclusion of solvent-accessible surface areas. All these terms represent the differences, upon binding, in the ensemble averages of pertinent quantities, obtained from molecular dynamics (MD) or Monte Carlo simulations of the complex and of single components. Here we report a modification of the LR approach by: (1) the replacement of the two energy terms through the single-point QM/MM energy of the time-averaged complex structure from an MD simulation; and (2) a rigorous consideration of multiple modes (mm) of binding. The first extension alleviates the force-field related problems, while the second extension deals with the ligands exhibiting large-scale motions in the course of an MD simulation. The second modification results in the correlation equation that is nonlinear in optimized coefficients, but does not lead to an increase in the number of optimized coefficients. The application of the resulting mm QM/MM LR approach to the inhibition of zinc-dependent gelatinase B (matrix metalloproteinase 9) by 28 hydroxamate ligands indicates a significant improvement of descriptive and predictive abilities. PMID- 17333484 TI - Bond-based 2D TOMOCOMD-CARDD approach for drug discovery: aiding decision-making in 'in silico' selection of new lead tyrosinase inhibitors. AB - In this paper, we present a new set of bond-level TOMOCOMD-CARDD molecular descriptors (MDs), the bond-based bilinear indices, based on a bilinear map similar to those defined in linear algebra. These novel MDs are used here in Quantitative Structure-Activity Relationship (QSAR) studies of tyrosinase inhibitors, for finding functions that discriminate between the tyrosinase inhibitor compounds and inactive ones. In total 14 models were obtained and the best two discriminant functions (Eqs. 32 and 33) shown globally good classification of 91.00% and 90.17%, respectively, in the training set. The test set had accuracies of 93.33% and 88.89% for the models 32 and 33, correspondingly. A simulated virtual screening was also carried out to prove the quality of the determined models. In a final step, the fitted models were used in the biosilico identification of new synthesized tetraketones, where a good agreement could be observed between the theoretical and experimental results. Four compounds of the novel bioactive chemicals discovered as tyrosinase inhibitors: TK10 (IC(50) = 2.09 microM), TK11 (IC(50) = 2.61 microM), TK21 (IC(50) = 2.06 microM), TK23 (IC(50) = 3.19 microM), showed more potent activity than L-mimose (IC(50) = 3.68 microM). Besides, for this study a heterogeneous database of tyrosinase inhibitors was collected, and could be a useful tool for the scientist in the domain of tyrosinase enzyme researches. The current report could help to shed some clues in the identification of new chemicals that inhibits enzyme tyrosinase, for entering in the pipeline of drug discovery development. PMID- 17333485 TI - 2DCSi: identification of protein secondary structure and redox state using 2D cluster analysis of NMR chemical shifts. AB - Chemical shifts of amino acids in proteins are the most sensitive and easily obtainable NMR parameters that reflect the primary, secondary, and tertiary structures of the protein. In recent years, chemical shifts have been used to identify secondary structure in peptides and proteins, and it has been confirmed that (1)H(alpha), (13)C(alpha), (13)C(beta), and (13)C' NMR chemical shifts for all 20 amino acids are sensitive to their secondary structure. Currently, most of the methods are purely based on one-dimensional statistical analyses of various chemical shifts for each residue to identify protein secondary structure. However, it is possible to achieve an increased accuracy from the two-dimensional analyses of these chemical shifts. The 2DCSi approach performs two-dimension cluster analyses of (1)H(alpha), (1)H(N), (13)C(alpha), (13)C(beta), (13)C', and (15)N(H) chemical shifts to identify protein secondary structure and the redox state of cysteine residue. For the analysis of paired chemical shifts of 6 data sets, each of the 20 amino acids has its own 15 two-dimension cluster scattering diagrams. Accordingly, the probabilities for identifying helix and extended structure were calculated by using our scoring matrix. Compared with existing the chemical shift-based methods, it appears to improve the prediction accuracy of secondary structure identification, particularly in the extended structure. In addition, the probability of the given residue to be helix or extended structure is displayed, allows the users to make decisions by themselves. PMID- 17333486 TI - Asymmetric Karplus curves for the protein side-chain 3J couplings. AB - The standard Karplus equation for calculating 3J coupling constants from any given dihedral angle requires three empirical coefficients be determined that relate to the magnitudes of three modes of the angle dependency of 3J. Considering cosine modes only (bimodal, unimodal and baseline component), Karplus curves are generally symmetric with respect to the sign of the angle argument. Typically, their primary and secondary maxima differ in amplitude, whereas the two minima are of equal depth. However, chiral molecular topologies, such as those surrounding the main-chain and side-chain torsions in amino-acid residues, preclude, as regards substituent positioning, exact mirror-image conformations from being formed--for any given torsion-angle value. It is therefore unlikely that 3J couplings assume identical values for the corresponding positive and negative dihedral angles. This suggests that a better empirical fit of the torsion-angle dependency of 3J could be obtained when removing the constraint of symmetrically identical coupling constants. A sine term added to the Karplus equation allows independent modelling of both curve minima typically located near dihedral-angle values of +90 degrees and -90 degrees. Revisiting an extensive 3J coupling dataset previously recorded to determine the side-chain torsions chi1 in the protein flavodoxin, the asymmetric Karplus model accomplishes a more accurate fit to the experimental data. Asymmetries revealed in the angle dependencies exceed the experimental precision in determining 3J. Accounting for these effects helps improve molecular models. PMID- 17333487 TI - New metabolic lung simulator: development, description, and validation. AB - OBJECTIVE: Indirect calorimetry, the determination of airway carbon dioxide elimination (V(CO2),and oxygen uptake (V(O2)), can be used to non-invasively detect non-steady state perturbations of gas kinetics and mirror tissue metabolism. Validation of monitoring instruments in patients is difficult because there is no standard reference measurement, a wide range of physiologic values is required, and steady state is difficult to achieve and confirm. We present the development, critical details, and validation of a practical bench setup of a metabolic lung simulator, to generate a wide range of accurate, adjustable, and stable reference values of V(CO2) and V(O2), for development, calibration, and validation of indirect calorimetry methodology and clinical monitors. METHODS: We utilized a metered alcohol combustion system, which allowed safe, precise, and adjustable delivery of ethanol to a specially designed wick system to stoichiometrically generate reference V(CO2) and V(O2). Gas was pumped through a circular circuit between the separate metabolic chamber and mechanical lung, to preserve basic features of mammalian gas kinetics, including a physiologic ventilation waveform and the ability to induce non-steady state changes. Accurate and precise generation of V(CO2) and V(O2) were validated against separate measurements of gas flow and gas fractions in a collection bag. RESULTS: For volume control ventilation, average error for V(CO2) and V(O2) was -0.16% +/- 1.77 and 1.68% +/- 3.95, respectively. For pressure control ventilation, average error for V(CO2) and V(O2) was 0.90% +/- 2.48% and 4.86% +/- 2.21% respectively. Low values of measured ethanol vapor and carbon monoxide supported complete and pure combustion. CONCLUSIONS: The comprehensive description details the solutions to many problems, to help future investigations of metabolic gas exchange and contribute to improved patient monitoring during anesthesia and critical care medicine. PMID- 17333489 TI - A Heideggerian defense of therapeutic cloning. AB - Debates about the legitimacy of embryonic stem-cell research have largely focused on the type of ethical value that should be accorded to the human embryo in vitro. In this paper, I try to show that, to broaden the scope of these debates, one needs to articulate an ontology that does not limit itself to biological accounts, but that instead focuses on the embryo's place in a totality of relevance surrounding and guiding a human practice. Instead of attempting to substantiate the ethical value of the embryo exclusively by pointing out that it has potentiality for personhood, one should examine the types of practices in which the embryo occurs and focus on the ends inherent to these practices. With this emphasis on context, it becomes apparent that the embryo's ethical significance can only be understood by elucidating the attitudes that are established towards it in the course of specific activities. The distinction between fertilized embryos and cloned embryos proves to be important in this contextual analysis, since, from the point of view of practice, the two types of embryos appear to belong to different human practices: (assisted) procreation and medical research, respectively. In my arguments, I highlight the concepts of practice, technology, and nature, as they have been analyzed in the phenomenological tradition, particularly by Martin Heidegger. I come to the conclusion that therapeutic cloning should be allowed, provided that it turns out to be a project that benefits medical science in its aim to battle diseases. Important precautions have to be taken, however, in order to safeguard the practice of procreation from becoming perverted by the aims and attitudes of medical science when the two practices intersect. The threat in question needs to be taken seriously, since it concerns the structure and goal of practices which are central to our very self understanding as human beings. PMID- 17333488 TI - Alterations in triad ultrastructure following repetitive stimulation and intracellular changes associated with exercise in amphibian skeletal muscle. AB - This study used Rana temporaria sartorius muscles to examine the effect of fatiguing electrical stimulation on the gap between the T-tubular and sarcoplasmic reticular membranes (T-SR distance) and the T-tubule diameter and compared this with corresponding effects on resting fibres exposed to a range of extracellular conditions that each replicate one of the major changes associated with muscular activity: membrane depolarisation, isotonic volume increase, acidification and intracellular lactate accumulation. Following each treatment, muscles were immersed in isotonic fixative solution and processed for transmission electron microscopy (TEM). Mean T-SR distances were estimated from orthogonal intercepts to provide estimates of diffusion distances between T and SR membranes and T-tubule diameter was estimated by measuring its shortest axis in the sampled J-SR complexes. Measurements from muscles fatigued by low frequency intermittent stimulation showed significant (P << 0.05) reversible increases in both T-SR distance and T-tubule diameter from 15.97 +/- 0.37 nm to 20.15 +/- 0.56 nm and from 15.44 +/- 0.60 nm to 22.26 +/- 0.84 nm (n = 40, 30) respectively. Exposure to increasing concentrations of extracellular [K(+)] in the absence of Cl(-) to produce membrane depolarisation without accompanying cell swelling reduced T-SR distance and increased T-tubule diameter, whilst comparable increases in [K(+)](e) in the presence of Cl(-) suggested that isotonic cell swelling has the opposite effect. Acidification alone, produced by NH(4)Cl addition and withdrawal, also decreased T-SR distance and T-tubule diameter. A similar reduction in T-SR distance occurred following exposure to extracellular Na-lactate where such acidification was accompanied by elevations of intracellular lactate, but these conditions produced a significant swelling of T tubules attributable to movement of lactate from the cell into the T-tubules. This study thus confirms previous reports of significant increases in T-SR distance and T-tubule diameter following stimulation. However, of membrane depolarisation, isotonic cell swelling, intracellular acidification and lactate accumulation, only isotonic cell swelling increases T-SR distance whilst membrane depolarisation and intracellular lactate likely contribute to the observed increases in T-tubule diameter. PMID- 17333490 TI - Nursing Schadenfreude: the culpability of emotional construction. AB - The purpose of this paper is to examine the concept of Schadenfreude--the pleasure felt at another's misfortune--and to argue that feeling it in the course of health care work, as elsewhere, is evidence of a deficient character. In order to show that Schadenfreude is an objectionable emotion in health care work, I first offer some conceptual remarks about emotions generally and their differential treatment in Kantian and Aristotelian thought. Second, I argue that an appreciation of the rationality of the emotions is crucial to our self understanding as persons in general and nurses in particular. Third, I present a critique of Portmann's (2000, When Bad Things Happen to Other People. London: Routledge) defence of Schadenfreude with examples from both nursing and medical scenarios. Specifically, I show how his exculpation of the emotion in terms of low self-esteem and a commitment to justice are not compelling. I argue that we are active in the construction of our emotional experiences of Schadenfreude, how we may indeed 'nurse' the emotion, and thus become culpable for them in ethical terms. PMID- 17333491 TI - Autonomy and informed consent: a mistaken association? AB - For decades, the greater part of efforts to improve regulatory frameworks for research ethics has focused on informed consent procedures; their design, codification and regulation. Why is informed consent thought to be so important? Since the publication of the Belmont Report in 1979, the standard response has been that obtaining informed consent is a way of treating individuals as autonomous agents. Despite its political success, the philosophical validity of this Belmont view cannot be taken for granted. If the Belmont view is to be based on a conception of autonomy that generates moral justification, it will either have to be reinterpreted along Kantian lines or coupled with a something like Mill's conception of individuality. The Kantian interpretation would be a radical reinterpretation of the Belmont view, while the Millian justification is incompatible with the liberal requirement that justification for public policy should be neutral between controversial conceptions of the good. This consequence might be avoided by replacing Mill's conception of individuality with a procedural conception of autonomy, but I argue that the resulting view would in fact fail to support a non-Kantian, autonomy-based justification of informed consent. These difficulties suggest that insofar as informed consent is justified by respect for persons and considerations of autonomy, as the Belmont report maintained, the justification should be along the lines of Kantian autonomy and not individual autonomy. PMID- 17333492 TI - Technology and the self. PMID- 17333493 TI - Edwards on disablement and personal identity. PMID- 17333494 TI - Antihypertensive drug utilization at health centres in a district of Istanbul. AB - OBJECTIVE: Since irrational use of antihypertensives has considerable clinical and economical consequences, this study was conducted to evaluate antihypertensive drug utilization in hypertension at seven State Health Centres in Istanbul. METHOD: A total of 297 hypertensive patients who accepted to participate in the study were evaluated by a face-to-face questionnaire and a copy of their prescriptions were collected for prescription analysis. RESULTS: Angiotensin-converting enzyme (ACE) inhibitors (31.7%), calcium channel blockers (28.8%), diuretics (16.2%), beta blockers (7.5%) and others (15.8%) have been prescribed. There were no statistically significant relation between prescribed antihypertensive drug groups and gender, age, and NSAIDs co-prescribing. The most frequent comorbidity in hypertensive patients was diabetes mellitus (10.4%) and calcium channel blockers (35.5%) have been prescribed to them as a first antihypertensive medication. Average cost per prescription was $42.7 +/- 38.1. According to the patients' self-reporting, the majority of them (85%) were prescribed without a physical examination. The physicians failed to write the prescriptions appropriately; only 5% of the scripts contained all information about the drug(s) and use instructions in full format. CONCLUSION: The present study indicates that GPs working at primary healthcare centres were rational in terms of antihypertensive drug choice. However, they poorly applied rational pharmacotherapy principles such as (a) writing a "good" prescription which is easily readable by the pharmacist and the patient and that contains full essential information; (b) a medical examination of the patient to assess her/his current clinical condition; and (c) taking care of not prescribing drugs with potential interaction like antihypertensives and NSAIDs together. PMID- 17333495 TI - Sedative-hypnotic treatment in an acute psychiatric setting: comparison with best practice guidance. AB - OBJECTIVE: The aim of this study was to review treatment patterns of sedative hypnotic agents within an acute adult inpatient psychiatric service, compare prescribing with best-practice recommendations for use and explore potential interventions. SETTING: Two urban acute inpatient psychiatric units in the Waitemata community. METHOD: A retrospective review of all consecutive admissions to these two adult psychiatric units was conducted during the period 1st January to 30th June 2002. Patient demographics, diagnosis and sedative-hypnotic treatment data were extracted from clinical files. Average benzodiazepine daily dose was calculated for each admission in diazepam equivalents (Diaz(e)). MAIN OUTCOME MEASURES: Sedative-hypnotic treatment administered, duration of treatment, average daily dose, and discharge treatment. RESULTS: Data from 257 patients and 293 admissions were analysed. Almost all admissions (86.7%) involved treatment with a sedative-hypnotic. A benzodiazepine was prescribed for 82.6% of admissions, of which 64.9% was administered on an "as-needed (prn)" basis. Zopiclone was used in 56.7% of admissions, of which 83.7% was "as-needed (prn)" treatment. Most benzodiazepine treatment was with a single agent (61.6%) and lorazepam was the most frequently prescribed (54.8%). Over two-thirds of admissions used benzodiazepine treatment for 50% or less of the admission duration. The duration of treatment was shortest in those with a diagnosis of schizophrenia/schizoaffective disorder. Almost two-thirds of admissions were discharged without any prescription for sedative-hypnotic treatment. CONCLUSION: The use of sedative-hypnotic treatment in the acute adult inpatient psychiatric environment compared favourably with best practice recommendations regarding dose, duration of treatment and discharge treatment. The study identified key areas for intervention by clinical pharmacists to ensure appropriate use of sedative-hypnotics including in-service education, regular review of all sedative hypnotic treatment and discharge medication planning. PMID- 17333496 TI - Contraindications to metformin therapy among patients with type 2 diabetes mellitus. AB - OBJECTIVE: The biguanide, metformin, is a commonly prescribed oral antihyperglycemic agent. However, there are several clinical conditions that are considered as contraindications to the use of metformin among patients with type 2 diabetes mellitus. The aim of this study was to investigate the presence and nature of contraindications to metformin therapy among patients with type 2 diabetes mellitus. METHOD: A retrospective study of the medical files of diabetic patients available at Alwosta clinic, north Palestine was carried out. Information about disease and medication profile of the patients was retrieved and analyzed using SPSS during the study period in 2004/2005. Focus was on metformin users who have contraindications to metfromin therapy. MAIN OUTCOME MEASURE: Presence and number of contraindications to metformin therapy. RESULTS: Two hundred and seventy-two type 2 diabetic patients were identified. One hundred and twenty four of those diabetic patients were metformin users. Approximately, 60% of patients in the metformin group had a least one contraindication. Congestive heart failure and renal impairment were the most quantitatively present contraindications. CONCLUSION: Contraindications to metformin therapy are common among type 2 diabetic patients and mostly disregarded. Patients have to be critically assessed before starting therapy and in case of metformin prescribing; dose should be adjusted based on the presence of risk factors for metformin adverse effects. PMID- 17333497 TI - Pharmacy care perspectives on problems with HIV antiretroviral therapy in Sweden. AB - OBJECTIVE: This study has three main objectives (1) to identify the major problems or difficulties pharmacy staff in Sweden experience regarding pharmacy care of patients receiving antiretroviral therapy, (2) to identify the perceptions of pharmacy staff regarding what are patient-related concerns with antiretroviral therapy and (3) to compare the extent to which pharmacy staff awareness matches patient perceptions regarding what are the major problems or difficulties associated with antiretroviral therapy. METHODS: A problem detection study (PDS) containing two questionnaires was conducted: one to be completed by pharmacy staff and another to be completed by both pharmacy staff and patients. In the latter survey, staff were asked about what they thought that patients would have responded. Staff and patient responses were then matched and compared with one another. RESULTS: The pharmacy staff expressed their need for continuous education so as to assist the patients with their complex regimens. The staff were aware that patients were worried about therapy failure and viral resistance, medication-related problems and negative attitudes from the public. The staff however were less aware of the extent to which patients worried about not having their HIV infection under control. The staff also valued written patient information to a much higher extent than the patients. CONCLUSIONS: The pharmacy staff' awareness of the major problems HIV patients are experiencing seems incomplete and may lead to lack of concordance between the patients and pharmacy staff. This in turn may lead to non-adherence and poor therapy outcomes. Pharmacy staff should be encouraged to improve and systematically assess patient issues regarding antiretroviral therapy. Through assessing patient needs and concerns, the pharmacists can better identify patient needs and thus better tailor their educational and behavioural interventions to improve therapy outcomes. PMID- 17333498 TI - Common problems with antiretroviral therapy among three Swedish groups of HIV infected individuals. AB - OBJECTIVE: The main objective of this study was to identify and compare the common problems and difficulties associated with combination antiretroviral therapy (CART) as experienced by three major groups of HIV infected individuals (homo- or bisexuals, former injecting drug users and origins of Sub-Saharan Africa) in Sweden. METHODS: Based on the results from in-depth interviews with 15 representatives from the three major groups, a questionnaire was designed for use in a problem detection study (PDS). The study was conducted with 195 HIV-positive patients residing in the major cities of Sweden. RESULTS: The overall response rate was 79%. The problems identified in all three groups were negative attitudes from the public, worries about disease progression or therapy failure, medication or drug-related problems and problems in connection to pharmacy visits. A specific problem in the homo- or bisexual group was drug-related problems such as adverse effects, drug interactions and pill burden. For former injecting drug users, the specific problem was disease-related conflicts with relatives and the problem of coping with the social and psychological burden caused by the HIV infection. The African group termed the risk of exposing their medication at the pharmacy as a specific problem, as this could reveal their HIV status. CONCLUSIONS: Our findings regarding problems with CART in three patient groups in Sweden may be of use to tailor pharmacy care to HIV infected individuals. General strategies to improve adherence need to be complemented with approaches that will address the specific needs for the different patient groups affected by HIV. Further studies on group-specific interventions that promote concordance and adherence to CART will be necessary to minimize therapy failure and viral resistance. PMID- 17333499 TI - Non-prescription medicines: a process for standards development and testing in community pharmacy. AB - OBJECTIVE: The objective of the study was to develop and test standards of practice for handling non-prescription medicines. METHOD: In consultation with pharmacy registering authorities, key professional and consumer groups and selected community pharmacists, standards of practice were developed in the areas of Resource Management; Professional Practice; Pharmacy Design and Environment; and Rights and Needs of Customers. These standards defined and described minimum professional activities required in the provision of non-prescription medicines at a consistent and measurable level of practice. Seven standards were described and further defined by 20 criteria, including practice indicators. The Standards were tested in 40 community pharmacies in two States and after further adaptation, endorsed by all Australian pharmacy registering authorities and major Australian pharmacy and consumer organisations. The consultation process effectively engaged practicing pharmacists in developing standards to enable community pharmacists meet their legislative and professional responsibilities. MAIN OUTCOME MEASURES: Community pharmacies were audited against a set of standards of practice for handling non-prescription medicines developed in this project. Pharmacies were audited on the Standards at baseline, mid-intervention and post-intervention. Behavior of community pharmacists and their staff in relation to these standards was measured by conducting pseudo-patron visits to participating pharmacies. RESULTS: The testing process demonstrated a significant improvement in the quality of service delivered by staff in community pharmacies in the management of requests involving non-prescription medicines. The use of pseudo-patron visits, as a training tool with immediate feedback, was an acceptable and effective method of achieving changes in practice. Feedback from staff in the pharmacies regarding the pseudo-patron visits was very positive. CONCLUSION: Results demonstrated the methodology employed was effective in increasing overall compliance with the Standards from a rate of 47.4% to 70.0% (P < 0.01). This project led to a recommendation for the development and execution of a national implementation strategy. PMID- 17333500 TI - Tuberous sclerosis successfully treated with levetiracetam monotherapy: 18 months of follow-up. AB - CASE: We present the case of a boy with tuberous sclerosis who was referred for evaluation and treatment of his intractable epileptic seizures, having failed multiple anti-epileptic drug trials. He was subsequently treated with Levetiracetam that was gradually titrated to an effective dose, achieving full suppression of his seizures. Thereafter, his concomitant anti-epileptic drugs were gradually reduced and eventually discontinued. He remained on monotherapy with Levetiracetam, which continued to fully control his seizures. His EEG tracings before and after treatment are presented and compared, showing normalization of the latter. CONCLUSION: Levetiracetam appears to be effective in treatment-resistant seizures which are symptomatic to tuberous sclerosis when used adjunctively as well as in monotherapy. This is the first report in the English literature regarding its use and efficacy in this condition. PMID- 17333501 TI - Simultaneous prescribing of atypical antipsychotics, conventional antipsychotics and anticholinergics-a European study. AB - OBJECTIVE: The aim of this study was to investigate to what extent atypical antipsychotics, conventional antipsychotics and anticholinergics are prescribed simultaneously in daily clinical practice in Europe. METHOD: A pharmaco epidemiological study was carried out in which hospital pharmacists from 45 hospitals in Belgium, Denmark, France, Germany, The Netherlands and Scotland participated. Prescription data for 2,725 patients (mainly inpatients) who had been using an atypical antipsychotic for more than 6 weeks were analysed. MAIN OUTCOME MEASURE: The frequencies of simultaneous prescription of atypical antipsychotics with other antipsychotics and/or anticholinergics. RESULTS: In this sample of patients with an atypical antipsychotic 42.1% was prescribed another antipsychotic (24.1% if low-potent antipsychotics were not included in the analysis) and 30.1% was prescribed an anticholinergic. In total 47.1% of patients were prescribed an atypical antipsychotic without any other antipsychotic or anticholinergic. CONCLUSION: It is common practice to prescribe a combination of atypical antipsychotics and conventional antipsychotics and/or anticholinergics. This suggests that monotherapy involving an atypical antipsychotic is not considered to be an adequate treatment for a substantial number of patients in clinical practice. PMID- 17333502 TI - Methyl allyl ether formation in plants: novel S-adenosyl L-methionine:coniferyl alcohol 9-O-methyltransferase from suspension cultures of three Linum species. AB - A novel 41 kDa methyltransferase displaying high regiospecificity towards the allylic hydroxyl moiety of coniferyl alcohol was cloned from suspension cultures of Linum nodiflorum L. and expressed in E. coli. The apparent K (m) for coniferyl alcohol is 7.23 microM with a V (max) of 707.5 pkat mg(-1) protein at 30 degrees C, whereas the K (m) for the co-substrate S-adenosyl-L-methionine is 18.5 microM. Structure-function relationship studies revealed stringent structure requirements. Even minor substructure deviations as the side-chain saturation or changes in the phenyl ring substitution result in activities decreased by 75-90%. Crotyl and allyl alcohols are not substrates, confirming that the aromatic ring itself is indispensable, and solely the derivatives with a C(3) side-chain are accepted. The enzyme shares only similarities under 46% on amino acid level with other known methyltransferases. The designated reaction product, coniferyl alcohol 9-methyl ether, could be detected in suspension cells. The highest content of up to 0.02% of the dry mass is concurrent with an increase of the specific enzyme activity that reaches its maximum of 3.94 pkat mg(-1) on day 6 of the culture period. Transcript levels estimated by semi-quantitative RT-PCR remain constant until day 6 and recede thereafter. The corresponding methyltransferase from Linum flavum L. differs mainly by one short variable fragment. Biochemical characterization revealed a higher catalytic efficiency and a slightly broader substrate plasticity together with a lower sensitivity to the presence of Zn(2+), Cu(2+) and Co(2+). This is to our knowledge the first report of a regiospecific allylic O-methylation of phenylpropanoids in plants. PMID- 17333503 TI - Functional characterization of two p-coumaroyl ester 3'-hydroxylase genes from coffee tree: evidence of a candidate for chlorogenic acid biosynthesis. AB - Chlorogenic acid (5-CQA) is one of the major soluble phenolic compounds that is accumulated in coffee green beans. With other hydroxycinnamoyl quinic acids (HQAs), this compound is accumulated in particular in green beans of the cultivated species Coffea canephora. Recent work has indicated that the biosynthesis of 5-CQA can be catalyzed by a cytochrome P450 enzyme, CYP98A3 from Arabidopsis. Two full-length cDNA clones (CYP98A35 and CYP98A36) that encode putative p-coumaroylester 3'-hydroxylases (C3'H) were isolated from C. canephora cDNA libraries. Recombinant protein expression in yeast showed that both metabolized p-coumaroyl shikimate at similar rates, but that only one hydroxylates the chlorogenic acid precursor p-coumaroyl quinate. CYP98A35 appears to be the first C3'H capable of metabolising p-coumaroyl quinate and p-coumaroyl shikimate with the same efficiency. We studied the expression patterns of both genes on 4-month old C. canephora plants and found higher transcript levels in young and in highly vascularized organs for both genes. Gene expression and HQA content seemed to be correlated in these organs. Histolocalization and immunolocalization studies revealed similar tissue localization for caffeoyl quinic acids and p-coumaroylester 3'-hydroxylases. The results indicated that HQA biosynthesis and accumulation occurred mainly in the shoot tip and in the phloem of the vascular bundles. The lack of correlation between gene expression and HQA content observed in some organs is discussed in terms of transport and accumulation mechanisms. PMID- 17333504 TI - The expression of iron homeostasis-related genes during rice germination. AB - To characterize Fe homeostasis during the early stages of seed germination, a microarray analysis was performed. mRNAs extracted from fully mature seeds or seeds harvested 1-3 days after sowing were hybridized to a rice microarray containing approximately 22,000 cDNA oligo probes. Many Fe deficiency-inducible genes were strongly expressed throughout early seed germination. These results suggest that the demand for Fe is extremely high during germination. Under Fe deficient conditions, rice produces and secretes a metal-cation chelator called deoxymugineic acid (DMA) to acquire Fe from the soil. In addition, DMA and its intermediate nicotianamine (NA) are thought to be involved in long distance Fe transport in rice. Using promoter-beta-glucuronidase (GUS) analysis, we investigated the expression patterns during seed germination of the Fe deficiency inducible genes OsNAS1, OsNAS2, OsNAS3, OsNAAT1, and OsDMAS1, which encode enzymes that participate in the biosynthesis of DMA, and the transporter genes OsYSL2 and OsIRT1, which are involved in Fe transport. All of these genes were expressed in germinating seeds prior to protrusion of the radicle. These results suggest that DMA and NA are produced and involved in Fe transport during germination. PMID- 17333505 TI - Natural diterpenes from Croton ciliatoglanduliferus as photosystem II and photosystem I inhibitors in spinach chloroplasts. AB - In our search for new natural photosynthetic inhibitors that could lead to the development of "green herbicides" less toxic to environment, the diterpene labdane-8alpha,15-diol (1) and its acetyl derivative (2) were isolated for the first time from Croton ciliatoglanduliferus Ort. They inhibited photophosphorylation, electron transport (basal, phosphorylating and uncoupled) and the partial reactions of both photosystems in spinach thylakoids. Compound 1 inhibits the photosystem II (PS II) partial reaction from water to Na(+) Silicomolibdate (SiMo) and has no effect on partial reaction from diphenylcarbazide (DPC) to 2,6-dichlorophenol indophenol (DCPIP), therefore 1 inhibits at the water splitting enzyme and also inhibits PS I partial reaction from reduced phenylmetasulfate (PMS) to methylviologen (MV). Thus, it also inhibits in the span of P(700) to Iron sulfur center X (F(X)). Compound 2 inhibits both, the PS II partial reactions from water to SiMo and from DPC to DCPIP; besides this, it inhibits the photosystem I (PS I) partial reaction from reduced PMS to MV. With these results, we concluded that the targets of the natural product 2 are located at the water splitting enzyme, and at P(680) in PS II and at the span of P(700) to F(X) in PS I. The results of compounds 1 and 2 on PS II were corroborated by chlorophyll a fluorescence. PMID- 17333506 TI - Time-resolved X-ray spectroscopy leads to an extension of the classical S-state cycle model of photosynthetic oxygen evolution. AB - In oxygenic photosynthesis, a complete water oxidation cycle requires absorption of four photons by the chlorophylls of photosystem II (PSII). The photons can be provided successively by applying short flashes of light. Already in 1970, Kok and coworkers [Photochem Photobiol 11:457-475, 1970] developed a basic model to explain the flash-number dependence of O2 formation. The third flash applied to dark-adapted PSII induces the S3-->S4-->S0 transition, which is coupled to dioxygen formation at a protein-bound Mn4Ca complex. The sequence of events leading to dioxygen formation and the role of Kok's enigmatic S4-state are only incompletely understood. Recently we have shown by time-resolved X-ray spectroscopy that in the S3-->S0 transition an interesting intermediate is formed, prior to the onset of O-O bond formation [Haumann et al. Science 310:1019 1021, 2005]. The experimental results of the time-resolved X-ray experiments are discussed. The identity of the reaction intermediate is considered and the question is addressed how the novel intermediate is related to the S4-state proposed in 1970 by Bessel Kok. This leads us to an extension of the classical S state cycle towards a basic model which describes sequence and interplay of electron and proton abstraction events at the donor side of PSII [Dau and Haumann, Science 312:1471-1472, 2006]. PMID- 17333508 TI - Light and growth temperature alter carbon isotope discrimination and estimated bundle sheath leakiness in C4 grasses and dicots. AB - We combined measurements of short-term (during gas exchange) and long-term (from plant dry matter) carbon isotope discrimination to estimate CO(2) leakiness from bundle sheath cells in six C(4) species (three grasses and three dicots) as a function of leaf insertion level, growth temperature and short-term irradiance. The two methods for determining leakiness yielded similar results (P > 0.05) for all species except Setaria macrostachya, which may be explained by the leaf of this species not being accommodating to gas exchange. Leaf insertion level had no effect on leakiness. At the highest growth temperature (36 degrees C) leakiness was lower than at the two lower growth temperatures (16 degrees C and 26 degrees C), between which no differences in leakiness were apparent. Higher irradiance decreased leakiness in three species, while it had no significant effect on the others (there was an opposite trend in two species). The inverse response to increasing irradiance was most marked in the two NAD-ME dicots (both Amaranthus species), which both showed almost 50% leakiness at low light (300 micromol quanta m(-2) s(-1)) compared to about 30% at high light (1,600 micromol quanta m( 2) s(-1)). NADP-ME subtype grasses had lower leakiness than NAD-ME dicots. Although there were exceptions, particularly in the effect of irradiance on leakiness in Sorghum and Boerhavia, we conclude that conditions favourable to C(4) photosynthesis (high temperature and high light) lead to a reduction in leakiness. PMID- 17333509 TI - Flank hernia and bulging after open nephrectomy: mesh repair by flank or median approach? Report of a novel technique. AB - Flank incisions may be associated with flank hernias, which may be complicated with incarceration and strangulation. Furthermore, they may cause a significant limitation of the patient's quality of life. In the period 1997-2006 we performed 15 flank hernia repairs with a prosthetic mesh implantation. From 1997 to 2001 hernias were managed with a standardized mesh implantation through the initial flank incision (seven cases, flank group). Since 2001 we have adopted a novel operative approach in eight patients. Through a median laparotomy and following a transabdominally reduction of the hernia sac, a prosthetic polypropylene mesh [Prolene, Vypro or UltraPro, Ethicon Endo-Surgery (Europe) GmbH, Norderstedt, Germany] overlapping the midline was placed in a sublay technique (median group). The perioperative complication rate was comparable and they consisted mostly of postoperative seromas. A patient from the flank group developed a hernia recurrence two months after surgery. Thirteen patients participated in the annual follow-up for a total follow-up time of five years. In this period we observed only one additional case of hernia recurrence: a patient of the flank group presented with a 3 cm hernia recurrence at the proximal end of the previous operative incision. No recurrence was observed in the median group. As a result the novel technique for open repair of flank incisional hernias we present permits a remodelling of the abdominal wall and is associated with excellent postoperative results. PMID- 17333510 TI - The effectiveness of a scientific symposium to change urologists' attitude towards treatment of LUTS/BPH. AB - PURPOSE: The use of interactive voting systems in continuing education helps to evaluate the alteration in the audience's views after a presentation. This study was designed to evaluate whether urologists' attitude towards management of benign prostate hyperplasia can be changed, and to estimate objectively the achievement of educational goals by using an interactive voting system. METHODS: The audience attitude was repetitively estimated by responding to questions using wireless keypads. Educational goal achievement was calculated by adding the percentage of those changing their opinion from "wrong" to "right" and that of those insisting on their initial "right" opinion. RESULTS: Giving a "wrong" answer and the probability of opinion change were independent of age and board certification. Being initially on the "wrong" side resulted in a greater probability of opinion change. The educational goals were achieved in 20.8-86.2% of cases. CONCLUSION: Satellite symposia are helpful learning environments. The use of an interactive voting system may help to evaluate objectively the achievement of educational goals. PMID- 17333511 TI - The effect of intravesical ketoprofen on acetylcholine-evoked urinary bladder contractility and detrusor overactivity in the anesthetized rabbit model. AB - Intraurethral procedures such as the transurethral resection of the prostate can generate detrusor overactivity and bladder irritability. The rabbit model of detrusor overactivity has proven to be an excellent model to study the effects of drugs on detrusor overactivity. Using this model, we evaluated the responses to intravesical ketoprofen. In this model, each rabbit is anesthetized and the right external carotid artery is cannulated for blood pressure monitoring. A catheter is inserted through the femoral artery and is used for administration of acetylcholine (Ach). The bladder is exposed and catheterized for bladder pressure monitoring and drug addition and the proximal urethra is ligated. Cystometry is performed, the bladder drained, and 20 ml buffer placed in the bladder. After 30 min Ach is injected proximal to the vesical artery and the response of the bladder and blood pressure is recorded. Ach administration is repeated at 10-min intervals until three consistent responses are obtained. The bladder is drained and 20 ml of ketoprofen (100 microM final concentration) is placed in the bladder. Ach injections are repeated as given above at 10 min intervals and observed for 4 h. At the end of the experiment, a second cystometry is performed. The following is a summary of the results: Ketoprofen had no effect on either micturition pressure or the intravesical volume at micturition. Ketoprofen administration resulted in a progressive 50% decrease in the response to Ach. Ketoprofen mediated a progressive decrease in detrusor overactivity amplitude and frequency, reaching a maximum at 120-180 min. PMID- 17333512 TI - Sonographically documented stable seminoma: a case report. AB - Seminoma of the testis has a diverse natural history. We report a unique case of histologically confirmed classic seminoma in a 32-year-old patient documented by ultrasound on two occasions one year apart. The tumor size did not change during that time. We explore the possibility of a dichotomy in growth within seminoma and the need to identify molecular methods to predict the subset of tumors that behave biologically less aggressive. PMID- 17333513 TI - Novel alterations in superoxide dismutase and catalase activities in the female rabbit bladder subjected to hormonal manipulations. AB - OBJECTIVES: Previous studies have demonstrated that ovariectomy induces reduced blood flow and hypoxia, resulting in free radical damage of the mucosal and smooth muscle compartments of the rabbit urinary bladder, whereas estradiol administration results in angiogenesis and recovery from hypoxia. The current study was designed to investigate the effects of ovariectomy and estradiol replacement on the superoxide dismutase (SOD) and catalase (CAT) activities of the bladder. METHODS: A total of 12 mature female rabbits were divided into three groups of four rabbits each: control, ovariectomy, and ovariectomy with 17-beta estradiol supplementation by subcutaneous slow-release tablet. The bladder body and base of the rabbits were examined after 2 weeks. The bladder body and base were separated into muscle and mucosa, and the tissues were analyzed for SOD and CAT activities. RESULTS: Quantitative SOD activities for the mucosa and muscle of both bladder body and base increased after ovariectomy when compared with those of controls. Estradiol replacement resulted in a significant decrease in the SOD activities in the body muscle. Ovariectomy caused a decrease in the CAT activities in the bladder tissues, whereas estradiol treatment resulted in significant increases. CONCLUSIONS: These data indicate that ovariectomy induced generation of reactive oxygen species (ROS), as evidenced by the enhanced SOD activity, indicating oxidative stress in the lower urinary tract. Estradiol replacement reversed the effects of ovariectomy; this finding suggests an anti oxidant effect of estradiol on the bladder. PMID- 17333514 TI - Endoscopic therapy of a massive rectal bleeding after prostate biopsy. AB - We report on the case of a 65-year-old man with an indication for a transrectal multibiopsy of the prostate based on a PSA value of 4.5 ng/ml. A massive haemoglobin effective rectal bleeding occurred post-intervention, which due to haemodynamic instability required the administration of erythrocyte concentrates. Both manual compression and rectal tamponade failed to stop the bleeding, and immediate haemostasis was achieved through an endoscopic injection of adrenaline. We present this case in detail and additionally describe current data on the complications of the ultrasound-guided transrectal biopsy of the prostate and the options for treating the fulminant rectal bleeding that is a consequence of this procedure. PMID- 17333515 TI - Laparoscopic repair of vesicovaginal fistula. AB - INTRODUCTION: In developed countries, the majority of vesicovaginal fistulas develop after gynaecologic surgery, with abdominal hysterectomy accounting for 90% of cases. Several techniques are available for repairing the fistulas. Abdominal approaches give good results even for difficult posterior located fistulas, but are associated with increased morbidity compared with the transvaginal approach. We performed a laparoscopic repair to minimize the surgical morbidity of the transabdominal approach. METHODS: A 44-year-old female presented with vesicovaginal fistula after abdominal hysterectomy. After a failed trial of conservative treatment with catheter drainage, a transperitoneal laparoscopic repair was performed. Cystoscopy was performed intially to confirm the fistula location and for bilateral ureteric catheterization. A 4-port technique was performed with the patient in the Trendelenburg position with her legs in lithotomy position. Without opening the bladder, the fistula tract was excised with separation of the bladder from the anterior vagina wall. Both the bladder and vagina walls were then closed separately using intracorporeal suturing with an interpositional omentum. RESULTS: The operation was uncomplicated. Total operative time was 260 min. Normal diet was resumed on day 1 and patient was discharged on the same day with an indwelling catheter. A cystogram performed 3 weeks post surgery showed resolution of the fistula. CONCLUSIONS: Laparoscopic repair of vesicovaginal fistula without opening the bladder and using intracorporeal suturing and omentum interpositioning is feasible in selected patients. PMID- 17333516 TI - Biosimilars: recent developments. AB - Biopharmaceuticals are recombinant protein drugs which are produced by biotechnology. The availability of such molecules has revolutionised the way we treat many diseases. However, the patents for many originator biopharmaceuticals are expiring, and a new generation of follow-on molecules, termed "biosimilars", are under development. Health care providers perceive biosimilars to be cheap replacements for originator drugs such as recombinant human erythropoietin and human growth hormone. However, concerns have been raised about the comparability of biosimilars with originator products especially in light of the complex manufacturing process required to produce biopharmaceuticals. The complexity of protein molecules renders it impossible to produce identical copies; this in turn raises questions on the safety of follow-on biosimilar products, particularly with respect to immunogenicity. This review briefly outlines the process of biopharmaceutical production, potential problems that can arise from their long term use in patients, and the issues facing regulatory bodies as they look to institute guidelines for new biosimilar molecules. PMID- 17333517 TI - Lunar phases and zodiac signs do not influence quality of radical cystectomy--a statistical analysis of 452 patients with invasive bladder cancer. AB - OBJECTIVE: To determine the influence of the lunar phases and the position of the moon in the zodiac on the frequency of complications and the survival of bladder cancer patients after radical cystectomy. It has been postulated that radical cystectomy performed during the waxing moon, or particularly at full moon, or at the zodiac sign Libra is associated with a poorer outcome. MATERIAL AND METHODS: We tested this hypothesis by evaluating the progression-free survival, the complication rate and the re-operation rate for 452 consecutive patients after radical cystectomy. In this retrospective review, the dates of surgery were allocated to the lunar phases and the zodiac signs. Based on these classifications, the patients were placed in groups which combined the lunar phase laws and differentiated between evidently unfavorable (full moon or waxing moon and/or the zodiac sign Libra; assigned to group 1) and favorable periods for surgery (new moon or waning moon and other signs of the zodiac apart from Libra; assigned to group 2). The mean follow-up was 49 months (range 0-158 months). RESULTS: A total of 244 patients (54%) were operated during an unfavorable period (group 1) and 208 (46%) patients during the auspicious period (group 2). The mean age, gender and kind of urinary derivation did not differ significantly in the two groups. Pathological tumor stages were evenly distributed according to the lunar phase groups (P = 0.713). We found no significant differences in the perioperative mortality rates, early re-operation rates, early complications, and late complications across the two groups. No significant differences in progression-free survival were observed when timing of cystectomy during the lunar cycle was considered (P = 0.231). CONCLUSIONS: Our analysis demonstrated no predictable influence of the lunar phase on survival or complications. Although this was not a prospective randomized trial, the statistical magnitude of the results do not support any recommendations for scheduling patients for radical cystectomy at any particular day of the lunar phase. PMID- 17333518 TI - Persistent mullerian duct syndrome with transverse testicular ectopia. AB - A 15-month-old boy was discovered to have internal female genitalia during an operation for bilateral inguinal hernia. The biopsies showed normal testicular tissue and the karyotyping result was 46XY, so the diagnosis of persistent mullerian duct syndrome (PMDS) was made. At the second operation, the uterine fundus and fallopian tubes were excised. Then, he underwent bilateral orchiopexy. We discuss a rare presentation of this disorder, its management, and genetic implications together with a review of the literature. PMID- 17333519 TI - Lower urinary tract symptoms, prostate volume, uroflowmetry, residual urine volume and bladder wall thickness in Turkish men: a comparative analysis. AB - AIM: To evaluate the association between lower urinary tract symptoms (LUTS) severity and bladder wall thickness (BWT). MATERIALS AND METHODS: The study included 155 patients referred to outpatient clinics for LUTS. Patients were divided into three groups due to their IPSS. Group A included the patients with mild symptoms, group B included patients with moderate symptoms and group C included patients with severe symptoms. The patients were again divided into two groups due to their uroflowmetry results. Group 1 included the patients whose Q (max) 10 ml/s. RESULTS: The mean BWT was 4.14 + 1.03 mm (from 3 to 9 mm). Although there was no difference between the IPSS groups in BWT (P = 0.325), it was statistically significant between uroflowmetry study groups (P < 0.01). CONCLUSIONS: BWT seems to be significantly increased in men who have Q (max) values smaller than 10 ml/s. PMID- 17333520 TI - Pathological review of internal genitalia after anterior exenteration for bladder cancer in women. Evaluating risk factors for female organ involvement. AB - To evaluate cancer involvement of internal female genitalia of patients undergoing anterior exenteration for clinically organ confined transitional cell carcinoma of the bladder, and identify potential preoperative risk factors. Charts and anterior exenteration specimens from 54 women with clinically organ confined transitional cell bladder cancer were retrospectively reviewed. Emphasis was given to the presence of internal genitalia involvement and or primary gynecologic pathology. Unsuspected internal genitalia involvement was reported in only three patients (5.7%). The vagina was involved in two cases (3.8%) while the uterus in one (1.9%). In all cases involvement was due to direst extension from bladder tumors of the base and dome respectively. No preoperative variable could predict internal genitalia involvement in a statistical significant manner. Benign pathology of the female reproductive organs was observed in six patients and involved in all cases the uterus (11.5%). Internal genitalia involvement after radical cystectomy for TCC tumors of the bladder is rare (5.8%). Preoperative risk factors could not be identified although all involved genitalia were seen in tumors of the bladder dome and base. Therefore large multi institutional studies are needed in order to identify preoperative risk factors for internal genitalia involvement in females with bladder cancer. PMID- 17333521 TI - Safety and tolerability of extended-release oxybutynin once daily in urinary incontinence: combined results from two phase 4 controlled clinical trials. AB - Early studies of extended-release oxybutynin in patients with overactive bladder used adjusted-dose regimens ranging from 5 to 30 mg/day to achieve an optimal balance of efficacy and tolerability. The safety and tolerability of extended release oxybutynin at a fixed dose of 10 mg once daily (commonly prescribed in clinical practice) is reported using pooled data from 2 multicenter, randomized, double-blind, parallel-group trials with a similar study design. One study compared extended-release oxybutynin with immediate-release tolterodine 2 mg bid. The other study compared extended-release oxybutynin with extended-release tolterodine 4 mg qd. In total, 576 patients received extended-release oxybutynin, 399 received extended-release tolterodine, and 193 received immediate-release tolterodine. The incidence of adverse events (AEs) was similar in the three treatment groups (extended-release oxybutynin, 70%; extended-release tolterodine, 64%; and immediate-release tolterodine, 79%). The most common adverse event was dry mouth (extended-release oxybutynin, 29%; extended-release tolterodine, 22%; and immediate-release tolterodine, 33%). Other AEs occurring in more than 5% of patients in any treatment group included constipation, diarrhea, headache, urinary tract infection, pain, dyspepsia, and peripheral edema, with no apparent difference across treatment groups. Most AEs (>90%) were mild or moderate in intensity in all treatment groups. The proportion of patients who discontinued study medication due to AEs was 6.1, 4.8, and 7.8% in the extended-release oxybutynin, extended-release tolterodine, and immediate-release tolterodine groups, respectively. In total, 1.2, 1.0, and 1.6% of patients in the extended release oxybutynin, extended-release tolterodine, and immediate-release tolterodine groups, respectively, discontinued study medication due to dry mouth. PMID- 17333522 TI - Does the degree of experience for the tension-free vaginal tape procedure influence the results of the suprapubic arc sling procedure during the learning phase? AB - AIM: The object was to evaluate whether the degree of experience for the tension free vaginal tape (TVT) procedures influenced the early results of the suprapubic arc (SPARC) sling procedure. MATERIALS AND METHODS: We performed the TVT from March 1999 to May 2003 and SPARC from June to April 2004 by experienced surgeon (A) and inexperienced surgeon (B), respectively. Patients were divided as four subgroups: first 50 patients who underwent the TVT by surgeon A (TVT A); first 15 patients who underwent the TVT by surgeon B (TVT B); first 50 patients who underwent the SPARC by surgeon A (SPARC A); first 15 patients who underwent the SPARC by surgeon B (SPARC B). RESULTS: Bladder perforations were noted in 4 (8.5%) in the TVT A group and 2 (13.3%) in the TVT B group, respectively (P = 0.626). There was no bladder perforation occurred in the SPARC A and B groups. The rates of transient postoperative urinary retention were 6.4% in the TVT A group and 0.0% in the TVT B group, respectively (P = 1.000). No retention occurred in the SPARC A and B groups. Stress urinary incontinence was cured by 89.4% in the TVT A group and 80.0% in the TVT B group, respectively (P = 0.388). Similar success rates were found in the SPARC A (85.4%) and SPARC B (92.3%) group (P = 1.000). CONCLUSION: Our findings suggest that the degree of experience for the TVT procedure does not influence the results of the SPARC procedure during the learning phase. PMID- 17333523 TI - The effect of squamous and/or glandular differentiation on recurrence, progression and survival in urothelial carcinoma of bladder. AB - INTRODUCTION: The effects of squamous and/or glandular differentiation in urothelial carcinoma of bladder on recurrence, progression and survival rate were evaluated in this study. PATIENTS AND METHODS: Between 1998 and 2003, a total of 223 patients who had been treated with transurethral resection for bladder cancers were evaluated. The patients were divided into two groups as; Group I: tumor patients with squamous and/or glandular differentiation, Group II: patients without these findings. RESULTS: Histologically 189 (84.7%) were conventional urothelial carcinoma and 34 (15.2%) were tumors with squamous and/or glandular differentiation. The mean age of the patients was 64.4 +/- 12.7 (range 36-81) years. Survival rates within a period of 46.23 +/- 14.8 (12-67) months were 76.47% for Group I and 89.94% for Group II (P = 0.027). The stage distribution as pTa, pT1, and >/=pT2 was 2 (5.9%), 18 (52.9%), and 14 (41.2%) in Group I and 101 (53.4%), 51 (27%) and 37 (19.6%) in group II, respectively (P = 0.001). There was a statistically significant tendency towards higher stage at presentation in Group I and the grade distribution was significantly higher in Group I than Group II (P < 0.001). CONCLUSION: High recurrence rates and poor prognosis of these patients should be kept in mind in the follow-up period. In this respect, these patients should be followed up closely. PMID- 17333524 TI - Alternative strategies to evaluate the cost-effectiveness of peritoneal dialysis and hemodialysis. AB - BACKGROUND: Dialysis treatment requires considerable resources and it is important to improve the efficiency of care. METHODS: Files of all adult end stage renal disease (ESRD) patients who entered dialysis therapy between 1991 and 1996, were studied and all use of health care resources was recorded. A total of 138 patients started with in-center hemodialysis (HD) and 76 patients with continuous ambulatory peritoneal dialysis (CAPD). Four alternative perspectives were applied to assess effectiveness. An additional analysis of 68 matched CAPD HD pairs with similar characteristics was completed. RESULTS: Cost-effectiveness ratios (CER; cost per life-year gained) were different in alternative observation strategies. If modality changes and cadaveric transplantations were ignored, annual first three years' CERs varied between $41220-61465 on CAPD and $44540 85688 on HD. If CAPD-failure was considered as death, CERs were $34466-81197 on CAPD. When follow-up censored at transplantation but dialysis modality changes were ignored, CERs were $59409-95858 on CAPD and $70042-85546 on HD. If observation censored at any change of primarily selected modality, figures were $57731-66710 on CAPD and $74671-91942 on HD. There was a trend of lower costs and better survival on CAPD, the only exception was the strategy in which technical failure of modality was considered as death. Figures of the matched CAPD-HD pairs were very close to the figures of the entire study population. CONCLUSIONS: Compared to HD, CERs were slightly lower on CAPD. PMID- 17333525 TI - Structural features of three ureterocele calculi. AB - Ureterocele calculi are developed in cavities with urinary retention but far from the upper renal cavities. The structural features of three ureterocele calcium oxalate stones were observed by scanning electron microscope coupled with X ray microanalysis. The urinary parameters of the three patients were also determined. The stone A consisted of loose structure of large calcium oxalate dihydrate crystals and small spheres of hydroxyapatite. The interior contains disorganized plate-like calcium oxalate monohydrate crystals. The stone B was formed by a compact outer layer of calcium oxalate monohydrate columnar crystals. The structure of stone interior was similar to the stone A. The stone C was formed by concentric layers composed of either calcium oxalate monohydrate columnar crystals or hydroxyapatite. The core consisted of agglomerated calcium oxalate monohydrate crystals, hydroxyapatite and organic matter. From the urinary biochemical data it was deduced that two ureterocele patients (who formed A and B stones) were hypercalciuric (calcium > 300 mg/24 h), being 6.5 the urinary pH value of the patient that formed the A stone, and 7.0 the urinary pH of the patient that formed the C stone. The rest of urinary parameters for the three patients were normal. Thus, one of the requisite conditions for unattached stone development is the existence of a place inside the urinary tract where the solid particles that act as calculus initiator of the stone can be retained enough time to exert this action. PMID- 17333526 TI - What is the best predictor of postoperative erectile function in patients who will undergo coronary artery bypass surgery? AB - PURPOSE: The aim of this prospective study was to evaluate the impact of extracorporeal circulation and cross clamping period on erectile function in patients undergoing coronary artery bypass surgery (CABS). MATERIALS AND METHODS: A total of 50 patients undergoing CABS were evaluated in this prospective study. Before and 6-12 months after the CABS, patients were interviewed for erectile dysfunction (ED) using the International Index of Erectile Function (IIEF). Scoring the IIEF domain of erectile function allowed the classification of each patient as having no (26-30), mild (17-25), moderate (11-16) or severe (0-10) ED. Patients with normal, mild and moderate ED score were designated as group A, B and C, respectively. Patients were classified in 2 groups to evaluate the impact of extracorporeal circulation and cross clamping period on erectile function in patients undergoing CABS. Patients who had no change in ED score in group A and patients who had recovery in group B were included in group1. Patients who had impaired ED score in group A and group B were included in group 2. All patients were also interviewed for sociodemographic and relevant medical history. Sociodemographic data were age, job, marital status, alcohol, narcotic and smoking habit. Medical risk factors were diabetes, hypertension and psychiatric disorders. RESULTS: The mean age of patients included in the study were 46,6 (range 31-55). After the operation, 3 (7.5%) of 41 patients in group A had moderate, 1 (2.5%) had mild and 37 (90%) had no change in ED score. In group B, 2 (28%) of 7 patients had moderate, 4 (57%) had recovery in ED score, 1 had no change in ED score. There were only 2 patients in group C and 1 had severe, the other one had mild ED after the operation. The mean operation period was 234.8 m inutes in group 1 and 280 min in group 2. Cross clamping period and extracorporeal circulation of patients in group 1 and 2 were 33.2, 41.6 min and 54.7, 64.6 min, respectively. The groups were not statistically different with regard to mean operation, cross clamping and extracorporeal circulation period. CONCLUSION: Preoperative erectile function seems to be the best predictor of postoperative erectile function in patients who will undergo CABS. PMID- 17333527 TI - Combined use of percutaneous and transurethral instruments in the preadolescent children with intravesical pathologies. AB - The approach for the intravesical suspicious lesions or stones in the preadolescent children especially in boys is still a challenging problem. Open surgery, percutaneous suprapubic endoscopy or transurethral endoscopic approaches are the treatments of choice in children. However, there is a group in children between the ages of 10 and 12 years, which can be named as grey zone population; the length of the instruments is insufficient for transurethral intervention such as endoscopic stone extraction, transurethral bladder tumor resection especially for the lesion at the posterior bladder wall in this group. The aim of this study is to describe a new technique using laparoscopic instruments for percutaneous bladder stone and tumoral lesion and determines the efficacy of this procedure. Satisfactory results have been obtained in patients with these pathologies. In selected cases, operation time, urethral and mucosal damage, hospital stay, and cost can be decreased to a minimum with this simple technique. PMID- 17333528 TI - Inflammatory pseudotumor of urinary bladder - a diagnostic and management dilemma. AB - Inflammatory pseudotumors (IPT) are uncommon, benign, non-epithelial tumors of the urinary bladder. Only less than 30 cases have been reported so far in world's literature. The transititional cell carcinoma constitutes 90% of malignant epithelial tumors of urinary bladder. Large, endoscopically unresectable tumors require radical surgery. IPT resemble such tumors, morphologically, radiologically and clinically. The benign nature of this tumor warrants conservative surgical management, either transurethral resection or partial cystectomy. Awareness of this entity and its inclusion in the differential diagnosis may prevent unnecessary radical surgery. We report an unusual case of inflammatory pseudotumor of urinary bladder because of its diagnostic and management dilemma. PMID- 17333529 TI - Hydroxyurea therapy: a rare cause of reversible azoospermia. AB - BACKGROUND: Essential thrombocythaemia (ET) is an uncommon chronic myeloproliferative disorder characterized by a marked increase in the number of platelets. Hydroxyurea is effective in preventing thrombosis in high-risk patients with essential thrombocythaemia. In previous studies different side effects of Hydroxyurea have been pointed out, but attention has not really been focused on the possible side effects on spermatogenesis. CASE: A 35-year-old man under investigation for haematospermia and complaining of erythromyalgia was found to have a thrombocytosis with a platelet count of 1130 x 10(9)/l. Bone marrow aspiration confirmed a diagnosis of essential thrombocythaemia. He was commenced on hydroxyurea (2 g daily) in order to lower his platelet count and relieve the erythromyalgia. The patient represented to the urologists, 3 years later with infertility and a semen analysis done by his doctor had shown azoospermia. Monthly sperm counts after the withdrawal of hydroxyurea showed a gradual return of the spermatogenesis to normal over a period of around 6 months. The patient's wife had conceived within 4 months of him stopping hydroxyurea. CONCLUSION: This case highlights a very rare but nonetheless important side effect of treatment with hydroxyurea. Hydroxyurea can cause reversible inhibition of spermatogenesis and result in primary infertility. We believe that all patients being commenced on such treatment should be warned of this possibility and that they should be given the necessary follow-up investigations. PMID- 17333530 TI - Is it worth using daclizumab induction therapy with mycophenolate mofetil-based immunosuppressive regimens in live related donor kidney transplantation? A long term follow up. AB - BACKGROUND/AIMS: The aim of this work is to determine the long-term therapeutic benefit(s) of daclizumab induction therapy with triple immunosuppressive protocols including prednisolone, cyclosporine microemulsion (CsA), and mycophenolate mofetil (MMF) in the living related donor kidney transplantation. METHODS: Twenty-one adult recipients of their first kidney allograft were allocated to receive daclizumab with triple immunosuppressive therapy (steroids, CsA, and MMF). They were compared to 50 recipients of their first grafts who received a maintenance triple immunosuppressive therapy (steroids, CsA, and azathioprine). The patients were followed up for 5 years. RESULTS: Daclizumab group significantly experienced a marked reduction of acute rejection (7/21) when compared to the control group (31/50) with subsequent significant reduction of cumulative steroids doses at the end of 5 years. The overall incidence of post transplant complications was comparable among the two treatment groups. There was no significant difference in patients and graft survival; 5-year patient and graft survival were 95.3%, 85.7% for daclizumab and 96%, 88% for control group, respectively. CONCLUSIONS: Although prophylactic daclizumab with triple immunosuppressive protocol including MMF have drastically reduced the incidence of acute rejections, the graft and patient survival are unchanged in this long term follow up. PMID- 17333531 TI - Prevention of chronic cyclosporine nephrotoxicity in Sprague Dawely rats: role of colchicine and omega-3-fatty acids. PMID- 17333532 TI - Is the minimally invasive treatment as good as transurethral resection for benign prostatic hyperplasia? AB - Despite the development of new technologies, transurethral resection of the prostate (TURP) is still considered the gold standard for surgical treatment of the benign prostate hyperplasia (BPH). In general, new minimally invasive treatments have not demonstrated better outcomes than TURP in evidence based medicine trials published to date, and should be reserved for patients who prefer to avoid surgery, who are unsuitable candidates for surgery or who no longer respond favorably to medication. TUMT and TUNA appears to be more effective than medical therapy but less effective than TURP. Both treatments can be given under topical anesthesia or local prostatic or perineal block. Efficacy of transurethral vaporization appears similar to TURP, but the studies are short term and the glands operated on are relatively small. In patients with small prostates, the transurethral incision of the prostate can also be a good option, associated with less morbidity than TURP. Bipolar resection of the prostate is similar to TURP in effectiveness, but the data are inconclusive regarding blood loss, length of catheterization and hospital stay. Long-term comparative trials are needed to determine if the minimally invasive therapies are superior to standard TURP. PMID- 17333533 TI - Causes of death in older peritoneal dialysis patients--can we depend on registry reports? AB - OBJECTIVES: Despite significant improvements in renal management the mortality associated with dialysis care remains high. Many renal registries report mortality statistics on an annual basis. The objectives of this study were (1) to establish the accuracy of the registered cause of death (CoD) against that determined by a panel of physicians; and (2) to test the feasibility of using the HEMO study CoD classification system in patients on peritoneal dialysis (PD). SETTING: Single centre tertiary-care hospital. PATIENTS AND METHODS: Patients were selected from those aged > or = 65 years who died while receiving PD. The CoD was identified from that registered with the local renal registry, and from clinical records. MAIN OUTCOME MEASURES: (1) Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and kappa score comparing registered and extracted CoD. (2) The proportions of deaths in seven categories using two classification systems. RESULTS: A total of 51 patient charts were reviewed. The agreement between the registered and extracted CoD was poor for all causes of death except malignancy. Kappa scores ranged from 0.55 to 1.0 for different causes. PPV were poor for all except malignancy. Comparison of the CoD was highly dependent on the classification method used (e.g., death secondary to infection was 4% and 25% for CORR and HEMO, respectively). CONCLUSIONS: The registered CoD for patients who die while on PD is often inaccurate. Different policies for classifying deaths can have a significant effect on the final reports, which show the proportion of deaths attributed to different diseases. Standardization across registries is required. PMID- 17333534 TI - Karyotype evolution and phylogenetic relationships of hamsters (Cricetidae, Muroidea, Rodentia) inferred from chromosomal painting and banding comparison. AB - The evolutionary success of rodents of the superfamily Muroidea makes this taxon the most interesting for evolution studies, including study at the chromosomal level. Chromosome-specific painting probes from the Chinese hamster and the Syrian (golden) hamster were used to delimit homologous chromosomal segments among 15 hamster species from eight genera: Allocricetulus, Calomyscus, Cricetulus, Cricetus, Mesocricetus, Peromyscus, Phodopus and Tscherskia (Cricetidae, Muroidea, Rodentia). Based on results of chromosome painting and G banding, comparative maps between 20 rodent species have been established. The integrated maps demonstrate a high level of karyotype conservation among species in the Cricetus group (Cricetus, Cricetulus, Allocricetulus) with Tscherskia as its sister group. Species within the genera Mesocricetus and Phodopus also show a high degree of chromosomal conservation. Our results substantiate many of the conclusions suggested by other data and strengthen the topology of the Muroidea phylogenetic tree through the inclusion of genome-wide chromosome rearrangements. The derivation of the muroids karyotypes from the putative ancestral state involved centric fusions, fissions, addition of heterochromatic arms and a great number of inversions. Our results provide further insights into the karyotype relationships of all species investigated. PMID- 17333535 TI - A microsatellite-based, physically anchored linkage map for the gray, short tailed opossum (Monodelphis domestica). AB - The genome of the gray, short-tailed opossum, Monodelphis domestica, will be the first of any marsupial to be fully sequenced. The utility of this sequence will be greatly enhanced by construction and integration of detailed genetic and physical maps. Therefore, it is important to verify the unusual recombinational characteristics that were suggested by the 'first-generation' M. domestica linkage map; specifically, very low levels of recombination and severely reduced female recombination, both of which are contrary to patterns in other vertebrates. We constructed a new linkage map based on a different genetic cross, using a new and much larger set of map markers, and physically anchored and oriented the linkage groups onto chromosomes via fluorescence in-situ hybridization mapping. This map includes 150 loci in eight autosomal linkage groups corresponding to the eight autosome pairs, and spans 86-89% of the autosomal genome. The sex-averaged autosomal map covers 715 cM, with a full length estimate of 866 cM; the shortest full-length linkage map reported for any vertebrate. The sex-specific maps confirmed severely reduced female recombination in all linkage groups, and an overall F/M map ratio = 0.54. These results greatly extend earlier findings, and provide an improved microsatellite-based linkage map for this species. PMID- 17333537 TI - Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials. AB - X inactivation, the transcriptional silencing of one of the two X chromosomes in female mammals, achieves dosage compensation of X-linked genes relative to XY males. In eutherian mammals X inactivation is regulated by the X-inactive specific transcript (Xist), a cis-acting non-coding RNA that triggers silencing of the chromosome from which it is transcribed. Marsupial mammals also undergo X inactivation but the mechanism is relatively poorly understood. We set out to analyse the X chromosome in Monodelphis domestica and Didelphis virginiana, focusing on characterizing the interval defined by the Chic1 and Slc16a2 genes that in eutherians flank the Xist locus. The synteny of this region is retained on chicken chromosome 4 where other loci belonging to the evolutionarily ancient stratum of the human X chromosome, the so-called X conserved region (XCR), are also located. We show that in both M. domestica and D. virginiana an evolutionary breakpoint has separated the Chic1 and Slc16a2 loci. Detailed analysis of opossum genomic sequences revealed linkage of Chic1 with the Lnx3 gene, recently proposed to be the evolutionary precursor of Xist, and Fip1, the evolutionary precursor of Tsx, a gene located immediately downstream of Xist in eutherians. We discuss these findings in relation to the evolution of Xist and X inactivation in mammals. PMID- 17333538 TI - The search for a marsupial XIC reveals a break with vertebrate synteny. AB - X-chromosome inactivation (XCI) evolved in mammals to deal with X-chromosome dosage imbalance between the XX female and the XY male. In eutherian mammals, random XCI of the soma requires a master regulatory locus known as the 'X inactivation center' (XIC/Xic), wherein lies the noncoding XIST/Xist silencer RNA and its regulatory antisense Tsix gene. By contrast, marsupial XCI is imprinted to occur on the paternal X chromosome. To determine whether marsupials and eutherians share the XIC-driven mechanism, we search for the sequence equivalents in the genome of the South American opossum, Monodelphis domestica. Positional cloning and bioinformatic analysis reveal several interesting findings. First, protein-coding genes that flank the eutherian XIC are well-conserved in M. domestica, as well as in chicken, frog, and pufferfish. However, in M. domestica we fail to identify any recognizable XIST or TSIX equivalents. Moreover, cytogenetic mapping shows a surprising break in synteny with eutherian mammals and other vertebrates. Therefore, during the evolution of the marsupial X chromosome, one or more rearrangements broke up an otherwise evolutionarily conserved block of vertebrate genes. The failure to find XIST/TSIX in M. domestica may suggest that the ancestral XIC is too divergent to allow for detection by current methods. Alternatively, the XIC may have arisen relatively late in mammalian evolution, possibly in eutherians with the emergence of random XCI. The latter argues that marsupial XCI does not require XIST and opens the search for alternative mechanisms of dosage compensation. PMID- 17333542 TI - [Evidence-based methods must be prioritized in psychiatry!]. PMID- 17333543 TI - [The duration of sick leave may change if company physicians are given the responsibility]. PMID- 17333539 TI - The region homologous to the X-chromosome inactivation centre has been disrupted in marsupial and monotreme mammals. AB - Marsupial, as well as eutherian, mammals are subject to X chromosome inactivation in the somatic cells of females, although the phenotype and the molecular mechanism differ in important respects. Monotreme mammals appear to subscribe at least to a form of dosage compensation of X-borne genes. An important question is whether inactivation in these non-eutherian mammals involves co-ordination by a control locus homologous to the XIST gene and neighbouring genes, which play a key regulatory role in human and mouse X inactivation. We mapped BACs containing several orthologues of protein-coding genes that flank human and mouse XIST and genes that lie in the homologous region in chicken and frog. We found that these genes map to two distant locations on the opossum X, and also to different locations on a platypus autosome. We failed to find any trace of an XIST orthologue in any marsupial or monotreme or on any flanking BAC, confirming the conclusion from recent work that non-eutherian mammals lack XIST. We propose the region homologous to the human and mouse X-inactivation centre expanded in early mammals, and this unstable region was disrupted independently in marsupial and monotreme lineages. In the eutherian lineage, inserted and existing sequences provided the starting material for the non-translated RNAs of the X-inactivation centre, including XIST. PMID- 17333540 TI - Phosphorylation of the histone H3.3 variant in mitosis and meiosis of the urochordate Oikopleura dioica. AB - Mammalian histone variant H3.3 differs from replication-dependent histone H3.1 by five amino acids, including replacement of alanine 31 by serine. H3.3 is expressed throughout the cell cycle, primarily deposited at transcriptionally active loci independent of S-phase. Data from mammalian cells suggest that phosphorylation of serine 31 (H3.3S31P) plays a role in mitosis. Here we show that H3.3S31P also occurs during mitosis of the urochordate Oikopleura dioica, suggesting this histone modification and its function in mitosis is already present at the invertebrate-vertebrate transition. The spatial pattern differed from that of H3 phosphorylation at serine 28 (H3S28P). H3S28P was enriched near telomeric regions, but H3.3S31P differed both temporally and spatially from the mammalian pattern, being more widely distributed throughout prophase, prometaphase and metaphase chromosomes. We also identified an important role for H3.3S31P during oogenic meiosis in the semelparous O. dioica. H3.3S31P initiated together with H3S28P in all meiotic nuclei in late diplotene, after H3S10P. However, H3.3S31P was retained only on the subset of meiotic nuclei that seeded maturing oocytes and proceeded through meiosis to arrest in metaphase I. Thus, this epigenetic mark is part of a regulatory circuitry that enables O. dioica to numerically adjust oocyte production over two orders of magnitude. PMID- 17333544 TI - [SBU-report erroneously quoted in a Pfizer advertisement]. PMID- 17333545 TI - Bone screw data reveals significant price change activity. PMID- 17333548 TI - Carbon monoxide. PMID- 17333549 TI - The misuse of Social Security disability income on drug and alcohol abuse. PMID- 17333550 TI - The EHR debate rages on. PMID- 17333551 TI - Novel medicine to prevent fungal infections. PMID- 17333552 TI - Advisory on refrigeration of carrot juice. PMID- 17333553 TI - Plan B available over-the-counter for women 18 and older. PMID- 17333554 TI - First treatment for Hunter syndrome. PMID- 17333555 TI - Treatment for nerve-poisoning agents. PMID- 17333556 TI - Totally implanted heart. PMID- 17333557 TI - Generic drugs for osteoarthritis. PMID- 17333558 TI - Outreach program to teach safe medicine use to middle school children. AB - Medicine use isn't a typical part of the curriculum for middle school students. But a new educational outreach program is changing that. PMID- 17333559 TI - The FDA: fresh leafy greens grown in the United States are safe. AB - Every year, there are many thousands of pounds of fresh leafy greens, such as lettuce and spinach, grown in the United States and eaten by the public with no consequent illness. Outbreaks, however, such as the recent Escherichia coli (E. coli) O157:H7 outbreak linked to raw spinach, do occur, and there is a need to do everything possible to minimize the likelihood of further outbreaks and to prevent serious illness. The Food and Drug Administration has taken a number of actions in recent years, in partnership with other government agencies, to improve the safety of fresh leafy greens and is working on additional steps. From farm to table, everyone, including growers, processors, distributors, retailers and consumers, and government, has a responsibility to ensure food safety. PMID- 17333560 TI - Purchasing pet drugs online: buyer beware. PMID- 17333561 TI - Cracking down on health fraud. PMID- 17333562 TI - The FDA broadens access to lead screening test. AB - In September 2006, the Food and Drug Administration expanded the availability of the first simple and portable lead test system to more than 115,000 certified point-of-care locations nationwide, including health care clinics, mobile health units, and schools. This action will make it easier and faster for children and adults to be tested and treated for lead poisoning. PMID- 17333563 TI - The importance of patient-reported outcomes...it's all about the patients. PMID- 17333564 TI - New FDA test detects fake bioterror agents. AB - Some people have made phony terrorist threats involving bioterror agents such as anthrax (Bacillus anthracis). But the agents really turn out to be harmless substances. These actions have resulted in considerable economic loss and social anxiety. In a bid to alleviate the problem, researchers at the Food and Drug Administration's National Center for Toxicological Research (NCTR) are developing a quick, cost-effective way to distinguish fake materials from authentic bioterror agents. PMID- 17333565 TI - First of a kind in HIV treatment. AB - The Food and Drug Administration has approved Atripla Tablets, a fixed-dose combination of three widely used antiretroviral drugs in a single tablet for the treatment of HIV-1 infection in adults. Atripla is to be taken once a day alone or in combination with other antiretroviral products. PMID- 17333566 TI - Strengthening the regulation of clinical trials and bioresearch monitoring. AB - The Food and Drug Administration has announced new policy and regulatory developments to strengthen the agency's oversight and protection of patients in clinical trials and the integrity of resulting data. The Human Subject Protection and Bioresearch Monitoring (HSP/BIMO) initiative will help modernize the agency's approach to bioresearch monitoring of devices, foods, human drugs, biological drug products, and veterinary medicine. PMID- 17333567 TI - Relationship between elemental carbon, total carbon, and diesel particulate matter in several underground metal/non-metal mines. AB - Elemental carbon (EC) is currently used as a surrogate for diesel particulate matter (DPM) in underground mines since it can be accurately measured at low concentrations and diesels are the only source of submicrometer EC in underground mines. A disadvantage of using EC as a surrogate for DPM is that the fraction of EC in DPM is a function of various engine parameters and fuel formulations, etc. In order to evaluate how EC predicts DPM in the underground mining atmosphere, measurements of total carbon (TC; representing over 80% of the DPM) and EC were taken away from potential interferences in four underground metal/non-metal mines during actual production. In a controlled atmosphere, DPM mass, TC, and EC measurements were also collected while several different types of vehicles simulated production with and without different types of control technologies. When diesel particulate filters (DPFs) were not used, both studies showed that EC could be used to predict DPM mass or TC. The variability of the data started to increase at TC concentrations below 230 microg/m3 and was high (> +/- 20%) at TC concentrations below 160 microg/m3, probably due to the problem with sampling organic carbon (OC) at these concentrations. It was also discovered that when certain DPFs were used, the relationship between DPM and EC changed at lower DPM concentrations. PMID- 17333568 TI - Current world literature. Melanoma and other skin neoplasms. PMID- 17333569 TI - Current world literature. Transplantation. PMID- 17333570 TI - Recommended composition of influenza virus vaccines for use in the 2007-2008 influenza season. PMID- 17333571 TI - Influenza. PMID- 17333572 TI - Abstracts of the British Pharmaceutical Conference. September 4-6, 2006. Manchester, United Kingdom. PMID- 17333573 TI - Shaping up Europe. PMID- 17333575 TI - ECTRIMS 2006. Abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis. September 27-10, 2006. Madrid, Spain. PMID- 17333574 TI - A call for more research that enhances public health nutrition practice. PMID- 17333577 TI - Proprietary rights in body parts: the relevance of Moore's case in Australia. PMID- 17333576 TI - False-positive serum tricyclic antidepressant concentrations using fluorescence polarization immunoassay due to the presence of hydroxyzine and cetirizine. AB - A recent report indicates that hydroxyzine and its active metabolite cetirizine interfere with the PENTINA carbamazepine assay. The potential interference of hydroxyzine and cetirizine with the fluorescence polarization immunoassay (FPIA) and CEDIA assay of carbamazepine as well as with the fluorescence polarization immunoassay of tricyclic antidepressants (TCA) was studied. Aliquots of drug-free serum pools were supplemented with various concentrations of hydroxyzine and cetirizine representing therapeutic, mild to moderate toxic as well as very toxic concentrations. Then apparent carbamazepine and TCA concentrations were measured by immunoassays. Although no interference of hydroxyzine and cetirizine was observed with carbamazepine assays (FPIA and CEDIA), significant apparent TCA concentrations were observed when aliquots of drug-free serum were supplemented with hydroxyzine or cetirizine. Mathematical formula was devised to predict hydroxyzine and/or cetirizine concentration in serum based on observed apparent TCA levels. Hydroxyzine and cetirizine also falsely increased total TCA values when aliquots of serum pool prepared from patients receiving TCA were further supplemented with these drugs. In conclusion, hydroxyzine and cetirizine do not interfere with the FPIA and CEDIA carbamazepine assays but interfere with the measurement of total TCA using the FPIA. PMID- 17333578 TI - Ethical aspects of early diagnosis of genetic diseases. PMID- 17333579 TI - Ethical issues in genetics and aging: diagnosis, treatment, and prevention in the era of molecular medicine. PMID- 17333580 TI - The Christian and the new biology. PMID- 17333581 TI - From disparity to difference: how race-specific medicines may undermine policies to address inequalities in health care. PMID- 17333582 TI - The Lancet's editor Dr. Faith McLellan on publication ethics. PMID- 17333583 TI - The revolution in human genetics: implications for human societies. PMID- 17333584 TI - Genomic databases as global public goods? AB - Recent discussions of genomics and international justice have adopted the concept of 'global public goods' to support both the view of genomics as a benefit and the sharing of genomics knowledge across nations. Such discussion relies on a particular interpretation of the global public goods argument, facilitated by the ambiguity of the concept itself. Our aim in this article is to demonstrate this by a close examination of the concept of global public goods with particular reference to its use in the context of genomic databases. We content that the argument for construing genomics as a global public good depends on seeing it as a natural good by focusing on features intrinsic to genomics knowledge. We shall argue that social and political arrangements are relevant and that recognising this opens the door to construing the use of global public goods language as a strategic one. PMID- 17333585 TI - Special report: the efficacy and safety of statins in the elderly. PMID- 17333586 TI - Laparoscopic adjustable gastric banding for morbid obesity. PMID- 17333587 TI - The Human Genome Project, predictive testing and insurance contracts: ethical and legal responses. PMID- 17333588 TI - The role of genetic counseling in the elective termination of pregnancies involving fetuses with disabilities. AB - In this study, 69 women were surveyed who, as a result of a prenatal screening knew they were at risk for carrying a fetus with a disability. Results indicated that most women were referred by their physicians for genetic counseling either because of their age or because of an abnormal blood test. The majority of women indicated they would choose to terminate a pregnancy that tested positive for a disability, but the type of disability of the fetus, either Down syndrome or spina bifida, made no difference in the decision that women believed they would make. The women's intention to terminate a pregnancy appeared to be unrelated to their overall knowledge about disabilities but was negatively related to their knowledge of disability-related services. Although women reported that genetic counseling was helpful, they revealed that they were not given information about future-quality-of-life issues for individuals with disabilities nor provided with the positive as well as the negative aspects of giving birth to a child with disabilities. PMID- 17333589 TI - Whistling in the wind: patents on genetic research are a reality. It's time to reframe the debate. PMID- 17333590 TI - Public health, private genes: the social context of genetic biotechnologies. AB - The last decade has seen rapid discoveries in the genetic basis of disease associated with the Human Genome Project (HGP). Understanding the social (including legal, ethical and political) impact of the these findings, however, lags far behind. This paper addresses the social context of biotechnologies arising out of this project as well as the tension between the individual and collective uses of these technologies. The danger is that, in the context of a global trend towards conservatism, the ideology of genetic reductionism is legitimizing the abandonment of collectivist responses to social problems in favour of the promotion of individualist ones. In seeking to pursue health policy objectives of reducing premature morbidity and mortality more traditional public health concerns are in danger of being marginalized. PMID- 17333591 TI - The coming pharmacogenomics revolution: tailoring drugs to fit patients' genetic profiles. AB - The opportunity for increased precision in pharmaceutical therapy will represent one of the important legacies of the Human Genome Project. Medical researchers have long suspected that genetic differences account for some of the variability in patient response to drugs, but now they hope that the identification of single nucleotide polymorphisms will allow physicians to customize pharmaceutical interventions. Pharmacogenomics will lead to fundamental changes in how drugs are discovered, tested, manufactured, labeled, and marketed. Federal regulators, the courts, and other policy makers will face challenges in accommodating these changes, and, in turn, their responses may have important impacts on the maturation and diffusion of this technology. This Article describes these scientific developments as a prelude to asking whether legal institutions will manage to catch up to or, instead, hinder such advances. PMID- 17333592 TI - Eugenics stir emotions in Germany. PMID- 17333593 TI - A mix of mice and men. PMID- 17333594 TI - Va. apologizes to the victims of sterilizations. PMID- 17333595 TI - Could the cure for all diseases be banned? PMID- 17333596 TI - Only God can do that? Cloning and genetic engineering test the moral limits of science. PMID- 17333597 TI - Making babies? Genetic engineering and the character of parenthood. PMID- 17333598 TI - Female foeticide: a sociological perspective. PMID- 17333599 TI - Conflicting notions of personhood in genetic research. PMID- 17333600 TI - Reviewing the meaning of 'systematic review'. PMID- 17333602 TI - Cancer incidence and mortality in a New Zealand community potentially exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin from 2,4,5-trichlorophenoxyacetic acid manufacture. AB - OBJECTIVE: To investigate whether the rates of all cancers and four cancers (soft tissue sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease and chronic lymphocytic leukaemia) associated with dioxin exposure are higher in New Plymouth, the site of a former 2,4,5-T manufacturing plant, than for the rest of New Zealand. METHODS: Analysis of 1970-2001 cancer data from the New Zealand Cancer Registry was undertaken for New Plymouth and the rest of New Zealand. RESULTS: There is no evidence of an increased cancer risk apart from one period (1970-74), which falls partly outside the 1962-1987 manufacturing period if 10-year latency is assumed. For 1970-74, there was an elevated risk for all cancer incidence (SIR = 111, 95% CI 104-119), and for two of the four specific cancers that are associated with dioxin exposure (non-Hodgkin's lymphoma SIR = 175, 95% CI 121-246 and chronic lymphocytic leukaemia SIR = 251, 95% CI 144-408). CONCLUSIONS AND IMPLICATIONS: The results do not suggest an increased cancer risk among the New Plymouth population related to the period of 2,4,5-T manufacture, although the study's limitations mean the possibility of an undetectable small elevation in cancer risk cannot be excluded. Although TCDD exposure in the first few years of 2,4,5-T manufacture may have contributed to cancer incidence in 1970-74, unknown exposure(s) before the start of 2,4,5-T manufacture and chance are also possible explanations. PMID- 17333601 TI - Avoidable mortality in Victoria between 1979 and 2001. AB - OBJECTIVE: To describe trends in avoidable mortality (AM) in Victoria by sex, degree of socio-economic disadvantage and remoteness. METHODS: The analysis is based on mortality and population data for 1979-2001 supplied by the Australian Bureau of Statistics (ABS) for Victoria. Total and disease-specific AM rates were age standardised using the direct method. For the period between 1997 and 2001, comparisons of total AM rates by sex were made between metropolitan and rural local government areas (LGAs), and between LGAs grouped into quintiles based on socio-economic disadvantage and categories of remoteness. RESULTS: Total AM rates declined significantly (p < 0.05) in both males and females between 1979 and 2001, but were significantly higher in males compared with females. Total AM rates were significantly higher in rural compared with metropolitan LGAs, from 1997 to 2001 in males and in 1998 in females. Total AM rates in the least disadvantaged quintile were significantly lower than those in the most disadvantaged quintile over the entire five-year period in males and in three years in females. Total AM rates were highest in remote LGAs and lowest in highly accessible LGAs. There were significant declines in ischaemic heart disease, stroke and road traffic accident AM rates among males. In females, IHD, stroke, breast and colon cancer AM rates declined significantly. CONCLUSIONS AND IMPLICATIONS: Despite large declines in AM in Victoria, there are significant differences in rates between the sexes and in the population based on socio economic status or remoteness. These results provide opportunities for policy makers to prioritise public health and health services interventions, targeting population groups and specific disease conditions to reduce health inequalities. PMID- 17333603 TI - Co-occurrence and clustering of tobacco use and obesity in New Zealand: cross sectional analysis. AB - OBJECTIVE: To describe the co-occurrence and clustering/aversion of tobacco use and obesity in New Zealand. METHOD: Data were sourced from the 2002/03 New Zealand Health Survey, a nationally representative household survey that included measured body mass index (BMI) and self-reported smoking status. The association of cigarette smoking, obesity, and the combination of these risk factors with socio-demographic variables was analysed by multiple logistic regression. Clustering/aversion (defined as observed prevalence of [smoking + obesity] > or < expected prevalence, where expected prevalence = prevalence of [smoking] x prevalence of [obesity]) was also estimated. RESULTS: The joint prevalence of smoking plus obesity in the adult population (15+ years) was 4.5%. However, this was 10% for Maori and 8.5% for deprivation quintile 5. Adjusting for relevant covariates, Maori were twice as likely to have both risk factors as non-Maori. A smooth deprivation gradient was found, with deprivation quintile 1 (least deprived) only one-fifth as likely to have both risk factors as quintile 5 (most deprived). There was no evidence of clustering, and aversion (negative clustering) was demonstrated only for middle-aged adults and for Maori. DISCUSSION: Since smoking cessation is associated with weight gain, substantial aversion might have been expected across all subgroups, yet this was not found. The most likely explanations are that the extent of weight gain associated with smoking cessation has been overestimated or is often not sustained. Even so, health promotion and clinical interventions need to take the dually exposed population into account, addressing not only the unhealthy behaviours themselves but also the social context in which dual exposure occurs. PMID- 17333604 TI - Tobacco education: have New Zealand primary schools done their homework? AB - OBJECTIVE: To describe the content, delivery and evaluation of tobacco-related (smoke-free) education to pre-teen students and to compare this education with current best practice. METHOD: Postal survey to staff of 136 New Zealand (NZ) schools with primary-aged children. RESULTS: More than 90% of schools offered some form of education about the harmful effects of tobacco use and many relied on external providers for this education. CONCLUSION: Although most schools offered some form of smoke-free education, there was a lack of rigorous program evaluation, particularly of programs provided by external agencies. IMPLICATIONS: Smoking remains a significant health problem in NZ and improving the quality of smoke-free education for pre-teen students, before most young people initiate smoking, would be a positive step towards better health. PMID- 17333605 TI - Community attitudes towards the early detection of cancer in Victoria, Australia. AB - OBJECTIVES: To describe people's attitudes towards early detection of cancer. METHODS: We conducted a telephone survey of Victorian adults aged 18+ years, during April-May 2005, using a market research company. RESULTS: 1,502 (41%) people participated; 80% of respondents believed that detecting cancer early meant that treatment saved lives most of the time or always; 88% believed finding cancer early enabled more effective treatment most of the time or always; and 70% indicated they would want to be tested for a cancer even if no treatment were available. Two-thirds or more of adults considered survival would be very much improved by early detection for breast, melanoma and prostate cancers; 49% for bowel cancer, and 30% for lung cancer. CONCLUSIONS AND IMPLICATIONS: Community support for the early detection of cancer was evident even in the absence of effective treatment. There was a lower perceived survival benefit for the early diagnosis of bowel cancer, compared with breast or prostate cancer or melanoma. An education campaign is required that focuses on the gains associated with early detection and benefits of screening for bowel cancer. PMID- 17333606 TI - High hepatitis C incidence in new injecting drug users: a policy failure? AB - OBJECTIVE: Evidence of ongoing hepatitis C (HCV) transmission among injecting drug users (IDUs) suggests a need for a better understanding of seroconversion characteristics among new IDUs and other vulnerable subgroups. This study aimed to determine incidence of HCV and associated risk factors among new IDUs in Sydney. METHODS: IDUs who had injected drugs in the past six months and who were unaware of their antibody HCV status or knew their serostatus to be negative were recruited through street-based outreach, methadone clinics and needle and syringe programs in south-western Sydney. Anti-HCV negative IDUs (n = 215) were enrolled and followed-up at 3-6 monthly intervals. New IDUs (n = 204) were defined as aged below 30 years or injecting for < or = 6 years at baseline. RESULTS: A total of 61 seroconversions were observed and incidence was 45.8 per 100 person years. Independent predictors of seroconversion were duration of injecting < 1 year (IRR = 3.10; 95% CI 1.47-6.54), female gender (IRR = 2.0; 95% CI 1.16-3.45), culturally and linguistically diverse background (CALDB) (IRR = 2.03; 95% CI 1.06 3.89) and intravenous cocaine use (IRR = 2.37; 95% CI 1.26-4.44). While new IDUs shared common risk factors, strong associations were observed between HCV seroconversion and sharing syringes, sharing other injecting equipment and backloading in CALDB new IDUs. CONCLUSION: Incidence of HCV infection among new IDUs in Sydney is unacceptably high. IMPLICATIONS: Extremely high rates of incident infection among newly initiated CALDB IDUs indicate an urgent need for enhanced policy and resource commitments to reduce the vulnerability of this group to HCV and other blood-borne infections. PMID- 17333607 TI - Measuring psychological, social, and environmental influences on leisure-time physical activity among adults. AB - Many of the self-administered scales for measuring physical activity (PA) influences were originally developed for vigorous-intensity exercise, focus on only one domain of influence, and have not been evaluated for both reliability and validity using population-based samples. OBJECTIVE: This study describes the factorial validity and internal reliability of scales for measuring individual level psychological, social, and environmental influences on leisure-time PA among adults in the general population. METHOD: Constructs were identified from a literature review and formative research with a socio-economically diverse sample. Items were generated using previously developed scales and interview data. New items were pre-tested using reliability and principal components analyses, with data collected from a mail survey sent to a randomly selected population-based sample. Qualitative feedback was obtained from a convenience sample and expert panel. A second mail survey provided data for principal components and reliability analyses. RESULTS: Twenty-eight scales were factorially derived and 24 had acceptable or marginally acceptable levels of internal consistency with Cronbach's alpha values ranging from 0.65 to 0.91. CONCLUSIONS AND IMPLICATIONS: The 24 scales are suitable for researchers and practitioners interested in measuring individual-level influences on PA that are consistent with Social Cognitive Theory. More research is required to assess predictive validity, sensitivity to change and test/re-test reliability. PMID- 17333608 TI - The 2004 Australian prison entrants' blood-borne virus and risk behaviour survey. AB - OBJECTIVES: To assess the prevalence of blood-borne viruses and associated risk factors among prison entrants at seven Australian prisons across four States. DESIGN: Consecutive cross-sectional design. Voluntary confidential testing of all prison entrants for serological markers of human immunodeficiency virus (HIV), hepatitis C (HCV) and hepatitis B (HBV) over 14 consecutive days in May 2004. Demographic data and data related to risks for blood-borne virus transmission, such as sexual activity, body piercing, tattooing, and injecting drug use, were collected. RESULTS: National prevalence for HIV was 1%, hepatitis B core antibody 20%, and hepatitis C antibody 34%. Fifty-nine per cent of participants had a history of injecting drug use. Among injecting drug users, the prevalence of HIV was 1%, hepatitis C antibody 56%, and hepatitis B core antibody 27%. Forty-one per cent of those screened reported a previous incarceration. In the multivariate model, Queensland and Western Australian (WA) prison entrants were significantly less likely to test positive to HCV than those in New South Wales (NSW). Amphetamine was the most commonly injected drug in Queensland, Tasmania and WA. In NSW, heroin was the most common drug injected. In the multivariate analysis a history of injecting drug use, being aged 30 years or more, and a prior incarceration were positively associated with hepatitis C infection. For hepatitis B core antibody, age over 30 years and a history of injecting drug use were associated with an increased risk. CONCLUSIONS: The findings support the view that prisoner populations are vulnerable to blood-borne virus infection, particularly hepatitis B and C. Prisoner populations should be included in routine surveillance programs so as to provide a more representative picture of blood-borne virus epidemiology in Australia. PMID- 17333609 TI - Substance use, psychological distress and violence among pregnant and breastfeeding Australian women. AB - OBJECTIVE: To identify the population prevalence and demographic characteristics of pregnant and/or breastfeeding Australian women who use licit and illicit substances and their experience of psychological distress and violence. METHODS: Data from the 2004 National Drug Strategy Household Survey were used to determine the prevalence of substance use, psychological distress and violence experienced by pregnant and/or breastfeeding women. RESULTS: A total of 976 pregnant and/or breastfeeding women were included. These women were significantly less likely than non-pregnant women to consume alcohol (47% vs. 85%) or any illicit drug (6% vs. 17%); however, there was no significant difference in tobacco smoking (20% vs. 25%). Self-reported psychological distress was significantly more frequent in the non-pregnant group (42%) than in the pregnant group, irrespective of substance use status. At a population level, pregnant and/or breastfeeding women were not at a heightened risk of psychological distress or violence. DISCUSSION: These findings highlight the importance of targeting older, tertiary-educated and relatively affluent mothers and those living in regional areas for drug and alcohol education campaigns and treatment. IMPLICATIONS: Simplifying the National Health and Medical Research Council pregnancy-specific alcohol guidelines, improving clinician training, and increasing the availability of treatment options in rural and regional areas may assist in the identification, referral and provision of assistance to substance using pregnant/breastfeeding women. PMID- 17333610 TI - Screening for postnatal depression: not a simple task. AB - OBJECTIVE: To evaluate an established screening program for postnatal depression using the Edinburgh Postnatal Depression Scale (EPDS) in a rural Victorian shire. By protocol, all women were screened at three time points post delivery by maternal and child health nurses. The efficacy of this approach in detecting probable depression was examined and referral pathways analysed. METHODS: Records for a 12-month cohort of women giving birth in the shire were audited (n = 267). Information collected included EPDS scores, parity, mother's age, reasons for non completion, referral details and nurses' comments. Analysis was completed using database and SPSS programs. RESULTS: The process goal of screening on all three occasions was rarely achieved--a goal met for only 15.5% of women; 22% were never screened at all. The highest rate of screening was 50.6% at one month, falling to 38.1% at eight months. Reasons for non-screening varied, suggesting no simple remedy. The proportions of women identified as probably depressed at each screening point (3.1%, 4.8% and 9.2%) were considerably lower than statewide figures for rural women. Referrals of probably depressed women were mainly to GPs but the results were unclear. CONCLUSIONS: A well-established program of universal screening was not effective in detecting probable depression in women. There was little evidence of direct feedback from GPs about women referred as a result of screening and no collaborative planning for affected women. Before universal screening of women for postnatal depression can be recommended, better evidence of its feasibility and acceptability are required, alongside convincing evidence that screening leads to improved outcomes for women. PMID- 17333611 TI - Estimating the prevalence of fetal alcohol syndrome in Victoria using routinely collected administrative data. AB - OBJECTIVE: To establish the prevalence of fetal alcohol syndrome (FAS) in Victoria through the Victorian Birth Defects Register (VBDR). METHODS: A sample of live births from 1995-2002 was selected from the Victorian Perinatal Data Collection and VBDR based on reported microcephaly, FAS or maternal use of alcohol during pregnancy. Following ethics approval, medical records of mother and child were requested for 117 births. One hundred and nine of these were accessed and examined for factors related to FAS. Records were categorised as FAS, possible FAS, unable to categorise, or not FAS. RESULTS: From the VBDR the prevalence was calculated at 0.006 per 1,000 live births. Four additional possible cases of FAS increased this to 0.014 per 1,000 live births. Six cases were defined as 'unable to categorise' as alcohol use was unknown but other features of FAS were evident. Including these cases, plus five where some low level alcohol use was reported, increased the prevalence to 0.03 per 1,000 live births. Twenty-eight per cent of the audit population and 39% of the microcephalic cases had no information about maternal alcohol use recorded in the antenatal or babies' records. CONCLUSION AND IMPLICATIONS: The audit of medical records provided additional information regarding FAS prevalence in Victoria. This prevalence ranges from 0.01 to 0.03 per 1,000 live births. To accurately assess the extent of the problem, there needs to be improved reporting of alcohol use in pregnancy and a system in place to report cases diagnosed during and beyond the perinatal period to the VBDR. PMID- 17333612 TI - Immunisation coverage of Queensland indigenous two-year-old children by cluster sampling and by register. AB - OBJECTIVES: To obtain, through a survey, estimates of immunisation coverage in a birth cohort of Indigenous children, and to compare survey estimates with those obtained from the Australian Childhood Immunisation Register (ACIR) for the same birth cohort of Indigenous children. METHODS: Cluster sampling of a birth cohort of two-year-old Indigenous children across Queensland, stratified according to accessibility/remoteness from services, was undertaken in 2003. An innovative method of identifying participants was used. Survey results of 10 vaccine doses were compared with ACIR data. RESULTS: The survey obtained a 4% sample of the birth cohort (137 children). Universally recommended vaccines showed high levels of coverage at 12 and 24 months, and survey estimates were slightly higher than ACIR estimates. Diphtheria-tetanus-acellular pertussis vaccine dose 3 (DTPa3) coverage was 93.8% (95% CI 88.0-99.6) by 12 months on survey and 87.5% on ACIR. Coverage was not timely and a lag phase of 4-6 months occurred for each vaccine dose. Haemophilus influenzae type b vaccine dose 2 (Hib2), scheduled for the age of four months, reached 90% coverage by nine months of age in the survey children. CONCLUSION: Both methods reported here provided similar results. IMPLICATIONS: These data indicate that ACIR Indigenous reporting rates have increased and coverage estimates are comparable to those provided by a survey. Immunisation coverage appears to be high, and the main remaining challenge in further reducing vaccine-preventable disease in Indigenous children is to improve immunisation timeliness. PMID- 17333613 TI - Equitable access to dental care for an at-risk group: a review of services for Australian refugees. AB - OBJECTIVE: Despite the poor dental health of refugees, few specific services are available. This review maps public dental services for refugees across Australian jurisdictions, identifies gaps in provision, identifies barriers to accessing dental care, and provides recommendations for improving access and oral health promotion for this group. METHODS: Data were sought from the State and Territory services for: a) the survivors of torture; b) oral health care units; and c) auditors-general reports of dental services. Eligibility criteria and estimated waiting times for general dental services, criteria for access to emergency care and availability of interpreter services were reviewed. RESULTS: Marked variation exists across Australian jurisdictions in available dental services and criteria for access to public dental care for refugees. There is limited priority access to general dental services for refugees. Waiting times for public dental treatment in most, if not all, jurisdictions are unacceptably long (range 13-58 months). Few interpreter services exist for refugees seeking to access dental services. CONCLUSIONS: Access to dental services for refugees across Australia remains fragmented and limited, particularly in rural and regional areas. Refugees are not using services because of several barriers, including long waiting times, variation in assessment criteria, different eligibility criteria and limited interpreter services. Consequently, their pattern of service use does not accurately reflect their needs. IMPLICATIONS: Australia needs better co ordinated, more extensive dental services that are easily accessible for this very high risk group. Identification of refugees as a special needs group and provision of targeted interventions addressing barriers to care are needed to establish adequate dental care. PMID- 17333614 TI - Facilitating effective health promotion practice in a public health unit: lessons from the field. AB - OBJECTIVES: Health promotion is a core function of public health services and improving the effectiveness of health promotion services is an essential part of public health service development. This report describes the rationale, the process and the outcomes of a realignment designed to improve the effectiveness of health promotion activities in a public health unit (PHU) in New Zealand. METHODS: A practice environment analysis revealed several factors that were hindering the effectiveness of the health promotion unit's (HPU) activities. Two primary change mechanisms were implemented. The first was an outcomes-focused model of planning and service delivery (to support evidenced-based practice), the second was the reorganisation of the HPU from a topics-based structure to an integrated one based on a multi-risk factor paradigm of population health. RESULTS: During the realignment barriers were encountered on multiple levels. At the individual level, unfavourable attitudes to changes occurred because of a lack of information and knowledge about the benefits of evidence and research. At higher levels, barriers included resourcing concerns, a lack of organisational commitment and understanding, and tensions between the political need for expedient change and research and development need for timely consideration of the impact of different models of practice. CONCLUSIONS AND IMPLICATIONS: This realignment took place within the context of a changing public health environment, which is significantly altering the delivery of public health and health promotion. Realignments designed to facilitate more effective health promotion and public health practice will continue, but need to do so in the light of others' experience and debate. PMID- 17333615 TI - Inaccuracies in self-reported histories of non-melanoma skin cancer. PMID- 17333616 TI - A method of measuring recreational boating exposure. PMID- 17333617 TI - [Investigation of c-fos expression and NADPH-diaphorase activity in the spine cord and brain in the development of the neck muscle weakness in rats]. AB - The distribution of c-fos expression as a marker of neuronal activation and NADPH diaphorase reactivity were examined in the cervical spinal cord, limbic structures and hypothalamus in anaesthetized rats after fatigue induced by intermittent high-rate (100 s(-1)) electrical stimulation of the dorsal neck muscles (mm. trapezius and splenius). In comparison to the control or sham stimulated animals fatiguing stimulation induced significant increase in ipsilaterally in the C -C4 spinal segments and the contralateral central (Ce), medial (Me) nuclei, paraventricular nucleus of hypothalamus (Pa) and ventrolateral periaqueductal gray (VLPAG). In spinal cord the highest mean number of Fos-immunoreactive (Fos-ir) neurons per section was found in layers 1,4 and 5 (5.8 +/- 0.9, 13.1 +/- 0.9 and 11.1 +/- 0.7, P < 0.05) of the dorsal horn. The order of intensity of c-fos expression in different regions of the brain was as following sequence: Pa > VLPAG > Ce (447.7 +/- 23.5, 196.3 +/- 12.7, 104.6 +/- 12.3, respectively). About 50 % of double-labeled (Fos-ir and NADPH-diaphorase reactive) cells were found in Pa nucleus. Received data show that limbic structures, hypothalamus and VLPAG are involved in activation after neck muscle fatigue and might contribute to nociceptive processing and generation of the autonomic and affective components of the muscle pain. PMID- 17333618 TI - [Effects of changes in mitochondrial permeability transition of medullary neurons on arterial pressure in rats]. AB - In acute experiments on anaesthetized with urethane normotensive rats we studied effects of modulating the mitochondrial permeability transition (MPT) of the neurons in the medullary cardiovascular nuclei - nucleus of the tractus solitarius (NTS), paramedian reticular nucleus (PMn), n.ambiguus (AMB), and lateral reticular nucleus (LRN) on the systemic arterial pressure level (SAP). An increase in the MPT with injections of an inductor for MPT phenylarsine oxide (10(-12) M - 10(-8) M) into the medullary nuclei under exploration has been shown to induce the lowering in the SAP level in a dose-dependent manner. A decrease in the MPT of the medullary neurons with either cyclosporine A or melatonin (10(-12) M - 10(-10) M) resulted in hypertensive responses of the SAP. Effects of phenylarsine oxide injections into the medullary nuclei were attenuated after preliminary intravenous administration of L-arginine. The data obtained give evidence that functional activity of the medullary cardiovascular neurons and their effects depend to a large extent on the functional state of their mitochondria. PMID- 17333619 TI - [Effect of combined application of the synthetic luteinizing hormone-releasing hormone agonist and nonsteroidal antiandrogen on the reproductive system of male rats]. AB - The influence of combined use of different doses of LGRH agonist (Surfagon) and non-steroidal antiandrogen Flutamide (Niftolid) on the structure and functional state of accessory sexual glands and hypophyseal-gonadal system of rate males had been studied. Optimal ratio of the drug doses for achieving the best antiprostatic effect has been determined. It was shown that combined use of above mentioned drugs resulted in the potentiation of antiprostatic effects. A maximal effect was observed after 30 days of Surfagon administration in a dose of 50 mg/kg b.w. together with flutamid in a dose of 10 mg/kg. b.w. Such a combination of drugs is recommended for clinical approbation as therapy for prostate cancer. PMID- 17333620 TI - [Effects of estradiol on synthesis of corticosteroids, protein kinase A and C activity in the adrenal cortex of intact and orchiectomized rats]. AB - Estradiol treatment produced significant increase of total 11 hydroxycorticosteroids level in the blood of intact and castrated rats. Activity of protein kinase A increased in the cytosol and membrane fraction of adrenocorticocytes of intact and orchiectomized rats after estradiol influence. Activity of protein kinase C significantly raised in the cytosol and membrane fraction of adrenocortical cells in all investigated groups. Our results suggest that cAMP-dependent protein kinase A and protein kinase C mediate estradiol effects in adrenal cortex. PMID- 17333621 TI - [Voltage-activated potassium channels of the inhibitory interneurons of the hippocampus in culture]. AB - Potassium channels make up the largest family of voltage-activated channels and play a key role in maintenance of cell excitability and in transmission of information within the nervous system. The aim of this work was to find out the specific subtypes of voltage-activated potassium channels peculiar to GABAergic interneurons of rat hippocampal culture. It was shown that total depolarization evoked outward potassium current in any interneuron studied had the activation threshold about -50 mV. The specific Kv1 channels' blocker a-DTX influenced neither amplitude nor kinetics of total current, thus we excluded the participation of these channels in its forming. The transient A-current made up 9.4+/-1.3% of the amplitude of total current and had low sensitivity to 4-AP that was an evidence of the presence of Kv4 channels in hippocampal interneurons. The slow inactivating component of integral potassium current was relatively small and had the time constant of inactivation 3 +/- 0.15 s that is typical for delayed rectifier potassium channels of Kv2 and Kv3 subfamilies. The main contribution (83 +/- 1.7 % of total amplitude) to the integral current belonged to the non-inactivating current. Prolonged depolarization of any interneuron tested to -20 mV evoked a steady non-inactivating outward current with amplitude 100-400 pA and activation threshold about -60 mV. Retigabine shifted its I-V plot to more negative values and increased the amplitude at -20 mV by 66+/-14%. These facts can be evidence of the participation of KCNQ channels subfamily in the forming of non-inactivating current. But selective blockers of KCNQ channels linopirdine and XE991 had very small influence on steady-state outward current that means the current appears owing to activity of linopirdine-insensitive forms of KCNQ channels or channels of a different, unknown family. PMID- 17333622 TI - [Effect of hypothyroidism on glial fibrillary acid protein in the structures of the rat brain]. AB - The content and polypeptide composition of the glial fibrillary acid protein (GFAP) in the hemispheres' cortex, hippocamp, thalamus and brain stem in the condition of thyroid gland hypofunction in Wistar rats of different age (preadolescent rats five weeks old, pubertal rats five months old and old rats 18 - 20 months old) were investigated. Hypothyroidism was created by adding mercasolil (10 mg/kg) to the standard diet. At the end of experiment the level of thyrotropin and thyroxin in serum was defined with immunoenzyme method. It was established that experimental hypothyroidism caused significant increase 14-72% of the filament fraction GFAP content in the thalamus and brain stem (preadolescent rats) and in the thalamus and hemispheres' cortex (adult rats), Defragmented polypeptides with molecular weight 47 -37 kDa were revealed by immunoblotting. It is connected with the activation of cytosceletal changes of astroglia. There were changes in the group of old rats that is possibly a reason of reduced the flexibility of CNS. PMID- 17333623 TI - [Effect of high-dispersed silica on the cultured rat hepatocytes]. AB - Highdispersed silica (HDS) is an active substance of medicine "Siliks", which demonstrates high protein adsorption property and is used for hatching out toxic agents of protein origin. To discover new potential applications of this substance, it is necessary to study the direct effect of HDS on cell viability. We studied the effects of HDS in concentration 0,0001%, 0,001% and 0,01% on cultured rat hepatocytes at 4 and 24 hours. To estimate the number of alive vs. apoptotic and necrotic cells, fluorescent nucleic dyes Hoechst 33342 and propidium iodide were employed. Cells that underwent autophagic processes were estimated using a specific fluorescent autophagosome marker monodansylcadaverine. We show here that HDS has dose-dependent effect on cell death; the number of cells with apoptotic features increased after 4 hours and in greater extend after 24 hours of treatment with HDS. At the lowest concentration HSD did not significantly affect cell viability, and we observed decrease in postapoptotic necrosis in cell culture. The highest concentration of HSD dramatically increased cell death through both necrosis and apoptosis. At the same time, autophagic activity was suppressed by 0,01% HSD. PMID- 17333624 TI - [Biologically active thymic factors and melatonin-producing pineal function in mice in aging]. AB - The aging peculiarities of thymic factors influence on pineal gland function in CBA mice were investigated. It was shown that in serum of the adult mice (3-4 m) melatonin level increased significantly in 3 h after one injection of thymic preparation "thymaline". The activating influence ofthymaline depended on season and linked with increased level of thymic serum factor (FTS). Thymic stroma supernatant of adult mice with high FTS level increased melatonin-producing pineal function in vitro. There was no activating influence of thymic factors on pineal function of old mice (23-24 mo) in vivo and in vitro as well as the pineal seasonal reaction on the administration of thymaline. The importance of thymic factors influence on melatonine level for the immune system rhythmic functioning was discussed. PMID- 17333625 TI - [Characteristics of the frontal hypothalamic neuron reactions to the electrical stimulation of the cerebral cortex in cats]. AB - In acute experiments we have used the glass microelectrodes and registered outside cell's impulse activity of the cats' hypothalamic neurons. We used the serial stimulation during 5 s (with frequency impulse 12, 30, 100 s(-1)) to the hippocampus (zone CA3), pyriform, cingulated and proreal cortexes. We have compared the background impulse activity (in the bine) of the neurons with the impulse activity after the stimulation. Two types of the neuron' reactions in response to the cortical stimulations were defined, they consisted in the mean frequency changes to the impulse activity during stimulation and during period in 15-30 sec after completion the stimulation. It is shown that the most of hypothalamic neurons explored (and neurons of the preoptic region) have changed their impulse activity during period, which approached through 15-30 sec after completion the-high frequency (100 s(-1)) stimulation to the all cortical zones and the stimulation of hippocampwith frequency 30 s(-1). We supposed that the cortical stimulations have a significant effect on the impulse activity pattern of the rostral hypothalamic neurons PMID- 17333626 TI - [Molecular mechanisms of cytoprotective action of the plant proanthocyanidins in gastric lesions]. AB - The molecular defence mechanisms against ethanol- and stress-induced (WRS) gastric lesions under the action of plant proanthocyanidins from grapefruit-seed extract (GSE) were investigated. Pre-treatment with GSE (8-64 mg/kg/day) in dose dependent manner attenuated gastric lesions induced by 100% ethanol and WRS; the doses of GCE reducing these lesions by 50% (ID50) were 28 and 36 mg/kg/day, respectively and this protective effect was similar to that obtained with PGE2 analogue. Lesions reduction was also accompanied by improvement of gastric blood flow, antiradical action, increased mucosal generation of PGE2, antioxidant activity. PMID- 17333627 TI - [Age-dependent characteristics of signaling lipids in the liver and brain of rats]. AB - The effect of age on signaling lipids contents in rat liver and different brain regions (hippocampus, neocortex) were studied. The contents of free fatty acids in the brain, diacylglycerol in liver and ceramide in all tissues studied have been found to increase with age. Age-dependent accumulation of neutral and sphingolipids evokes the violation of cell sensitivity to extracellular signals. PMID- 17333628 TI - [Effect of ecopathogenic environmental factors on the system of antioxidant defense in different parts of the rat brain]. AB - Influence ofecopathogenic environmental (radiation-chemical) factors on activities of superoxiddismutase, catalase and total antioxidative activity (TAA) has been investigated in morphologically and functionally different parts of rat brain. It has been found that reaction of cells in brain cortex, subcortical structures and cerebellum to these factors in all cases is revealed through the antioxidant enzyme activities decrease in all studied brain structures but in various degrees. In brain cortex, which is characterized by higher metabolic level, functional complexity and specialization, the higher level of antioxidation defense is marked both in normal state and under the action of negative factors, that allows to maintain the prooxidation-antioxidation balance. Subcortical structures were more sensitive to the heavy metal impact. Compared to the action of single factors at chronic combined influence of radiation and heavy metals on the separate antioxidative enzymes a summation effect can be observed and at aforesaid joint impact on multi-component system of antioxidation defense a partial mutual evening-out of effects of radiation and chemical agents can be marked. PMID- 17333629 TI - [Gender-specific characteristics of mental capability in students of different specialties]. AB - Mental capability of higher school students of different specialties: technical (27 male and 35 female), natural (32 male and 30 female) and humanitarian (20 male and 26 female) were studied. The following parameters were studied: perception, attention, memory, thinking and mental capability. The results showed that the development of psychophysiological organization of informational processing system in higher school students of different specialties is characterized by geterocronyisms and depend on the field of professional training. The learning of technical specialties results in the new associative links set up and abstract concepts forming under the object analysis. The natural specialties promote of the cognitive functions development along with time interval perception forming. The humanitarian specialties are characterized by attention and associative thinking functions. PMID- 17333630 TI - Fertility restoration by the cryopreservation of oocytes and ovarian tissue from the position of biomedical ethics: a review. AB - The loss of fertility as a consequence of chemoradiotherapy is a considerable problem. It can affect the psychological equilibrium and quality of life for women cancer survivors. In recent years, the possibility of cryopresenrvation of ovarian tissue following auto transplantation, opens new promise in the attempt to restore fertility. In addition to psychological and ethical concerns of this procedure, there are risks of retransplantation of tumor cells and recurrence of malignancy. In this review we will focus on the most recent achievements in cryopreservation of oocytes and ovarian tissue and will attempt to answer questions about the safety and effectiveness of restoration of fertility by cryopreservation of oocytes or ovarian tissue. PMID- 17333631 TI - Politics and naturalism in the 20th century psychology of Alfred Binet. AB - Alfred Binet is internationally recognized as the "father" of the first intelligence test as well as the most faithful French representative of laboratory experimentalism. A historical analysis of his work is therefore necessary to get to a thorough comprehension of 20th century psychology. The present article, starting from Binet's intellectual path and from the suggestions of the previous historical literature, aims at providing fresh insights into Binet's work by trying to capture the intersections between Binet, his naturalistic culture and the political context in which he worked in the early 20th century, when he actively tried to apply experimental psychology to the pedagogical area. In fact, it is possible to underline, with reference to those years, an evident turn towards applications in Binet's psychological production. The article reconstructs the political and institutional background of Binet's research and shows how the naturalism and experimentalism he promoted were complementary to the solidarist conceptions that were particularly prevalent among those who supported his work during the Third Republic. PMID- 17333632 TI - The embodiment of reconciliation: order and change in the work of Frederic Bartlett. AB - Frederic Bartlett (1886-1969) was one of the most prominent figures in British academic psychology during the 20th century. His psychological work has had a mixed reception, but there is no doubt that it continues to be much cited. Bartlett and his work have also attracted considerable historical attention both within history of ideas accounts and in attempts to understand the establishment of British academic psychology. The present article argues that new light can be shed on Bartlett's writings by seeing them as repeatedly grappling with 2 interrelated themes: the preservation of order and the adjustment to changing conditions. The article illustrates the ways in which these themes ran through his major works and informed some of his key theoretical concepts before going on to examine some of the potential sources for these themes. PMID- 17333633 TI - Verification of C. G. Jung's analysis of Rowland Hazard and the history of Alcoholics Anonymous. AB - Extant historical scholarship in the Jungian literature and the Alcoholics Anonymous (AA) literature does not provide a complete picture of the treatment of Rowland Hazard by C. G. Jung, an analysis that AA co-founder Bill Wilson claimed was integral to the foundation of AA in theory and practice. Wilson's original report resulted in archivists and historians incorrectly calibrating their searches to the wrong date. The current work definitively solves the mystery of the timing of Hazard's treatment with Jung by placing his preliminary analysis with Jung in the year 1926, rather than 1930 or 1931. Previously unexamined correspondence originating from Jung, Hazard, his cousin Leonard Bacon, his uncle Irving Fisher, and his aunt Margaret Hazard Fisher is supplemented by relevant primary and secondary source material. PMID- 17333634 TI - "The full story by no means all told": Harry Stack Sullivan at Sheppard-Pratt, 1922-1930. AB - Harry Stack Sullivan (1892-1949) is well known for his interpersonal theory of mental illness, but little is known about how he actually worked as a clinician with patients. This article examines a pivotal time in Sullivan's career at Sheppard and Enoch Pratt Hospital in Baltimore from 1922 to 1930. Using clinical records as well as published writings, the article focuses on 2 crucial issues that are not fully addressed either in Sullivan's published writings or in past studies of him: first, his treatment as a gay psychiatrist of patients who he believed had homosexual orientations; second, the intellectual and institutional paradigm in psychiatry that influenced his practice. Finally, this article addresses the circumstances surrounding Sullivan's departure from Sheppard-Pratt, suggesting psychiatry's limited confrontation with the social stigmatization of homosexuality. PMID- 17333635 TI - Differentiating bipolar disorder from depression in primary care. AB - Because patients with bipolar disorder spend more time in the depressed phase than in the manic phase, many receive an incorrect diagnosis of unipolar major depression and receive inadequate or improper treatment for it, leading to a dramatically increased risk of morbidity and suicide. Greater diagnostic accuracy is needed. PMID- 17333636 TI - Abraham Lincoln and the 'Lincoln sign'. PMID- 17333637 TI - Better glycemic control in the hospital: beneficial and feasible. AB - Hospitalized patients fare better if their blood glucose levels are strictly controlled. To manage blood glucose effectively, hospitals need to set up formal programs. Attending physicians, endocrinologists, and nurses need to work as a team. Standardized forms with management guidelines are valuable. PMID- 17333638 TI - Choosing the right coronary test. PMID- 17333639 TI - What is the best test for a patient with classic angina? AB - Symptoms that suggest myocardial ischemia raise two questions: does the patient have severe, hemodynamically obstructive coronary artery disease, and is he or she at risk for premature death or an early, major nonfatal cardiac event? Noninvasive cardiac testing may help with the first question in patients with an intermediate risk of coronary artery disease, and with the second question in patients with either an intermediate or a high risk of disease. Although the diagnostic value of noninvasive tests may be overestimated owing to referral bias, these tests are powerful when used for prognostic purposes. In patients with a normal resting electrocardiogram and no prior revascularization, a regular exercise stress test without imaging should suffice. However, no randomized trials have been done to determine if this strategy leads to better outcomes than with empiric therapy. PMID- 17333640 TI - Understanding and minimizing late thrombosis of drug-eluting stents. AB - Although the safety profiles of drug-eluting stents are similar to those of bare metal stents in the short term, concern has arisen about their potential for late thrombosis (occurring > 30 days after implantation). Stent thrombosis is rare but potentially devastating and can result in ST-segment elevation myocardial infarction or death. The aim of this article is to review the incidence, predictors, pathology, and prevention of late thrombosis of drug-eluting stents. PMID- 17333641 TI - When and how to fix a 'hole in the heart': approach to ASD and PFO. AB - Abnormalities in the atrial septum range in severity from patent foramen ovale (PFO), a residual cardiac structure found in approximately 25% of the general population, to uncommon, complex lesions associated with significant shunt flow and heart enlargement. While correcting some of these abnormalities is beneficial, most other defects warrant correction only under very specific circumstances. PMID- 17333642 TI - Which ovarian masses need intervention? AB - Ovarian cancer is deadly if not detected early, but it is only one of many causes of pelvic masses, which are common. The physician's job is to determine if a mass is likely to be malignant and needing surgical evaluation. The best predictors of malignancy are a combination of factors that include the patient's age, family history, menopausal status, symptoms, findings on physical examination and imaging studies, and blood level of the cancer biomarker CA125. PMID- 17333651 TI - [Clinical psychiatry. Being close to the patient]. PMID- 17333653 TI - [Clinical psychiatry, towards a search for meaning]. PMID- 17333654 TI - [The art of meeting the patient]. PMID- 17333652 TI - [Living clinical psychiatry, concept or praxis?]. PMID- 17333655 TI - [Dementia and normality, clinical practice in psychogeriatrics]. PMID- 17333656 TI - [Clinical ambiance and teamwork]. PMID- 17333657 TI - [Group therapy activities and the nursing intention]. PMID- 17333658 TI - Medico - historical study of "Visucika" (Cholera). AB - The Sanskrit word Visucika refers to a condition in which vitiated vata dosa causes pain like pricking with a needle over the body. It occurs in a person suffering with ajirna (indigestion) and its detailed description is available in Ayurvedic literature. This disease has its existence in India since ancient times; it has also been referred in Mahaharata and Tripitikas. Its etiology, signs, symptoms, complications, prognosis and treatment etc. as described in Ayurveda may be correlated with the disease Cholera, which is commonly known as "Haiza" in Hindi. In Greek language, the word Cholera means a flow of bile or the bilious disease. Cholera is an acute infectious diarrheal disease, caused by comma bacillus or vibrio cholerae sero groups 01 or 0139. Aretaetus, Benjamin Rush, Chadwick, John Snow, Robert Koch, etc. were some of the pioneers in Cholera research. Medico- historical importance of Cholera, its transmission, description and references from Ayurvedic texts etc., are being presented in this article. PMID- 17333659 TI - Standardization of Ayurvedic formulations : a scientific review. AB - Safety and efficacy of a drug mainly depends on the method of preparation. To assess the quality of a finished product, there should be some basic standards as well as methods of preparation. There are several parameters for testing the quality of a chemical drug, which have, are true indicators. So, there is no problem in assessing a synthetic drug's quality. As far as the preparation used in Ayurvedic system of medicine, a drug formulation or design may not be a problem, because many formulations are well documented in classical texts. But, there is confusion with respect to standards to be followed while preparing a formulation as well as basic parameters to assess the quality of the finished product. In Ayurveda, pancavidhakasayakalpana are the basic pharmaceutical preparations, from which all the other preparations are developed. A specific method for each and every preparation and some basic standards of finished products are mentioned in Ayurvedic texts to maintain their quality. This information may some times vary from text to text. To overcome this problem Sarangdhara mentioned detailed information about various formulations with respect to their methods of preparation as well as basic standards and are documented in Sarangdhara Samhita. PMID- 17333660 TI - Important Ayurveda literatures from the manuscripts available from Orissa (Cikitsarnava). AB - In the treasure of Ayurvedic literature, many texts are missing or partially available. Only references or few verses from many such texts are mentioned in later texts. Unfortunately, a large number of Ayurvedic texts are unexplored till today are likely to exist in palm-leaf manuscripts, which are decaying or undergoing permanent annihilation. As such many unique and valuable information contained in these texts are being lost. Though several Institutions have taken up work on literary Research, only few texts have been published during past decades. The present paper highlights the salient features of the text 'Cikitsarnava' authored by Visvanath Sena of 16th century of Orissa. Though his text on Pathyapathya has already been published, which has got a place in the pages of history of Ayurveda, a very little is known about this important text on therapeutics. Various aspects of this text and its author have been discussed to bring it in to the knowledge of fraternity of Ayurvedic physicians and Sanskrit scholars. PMID- 17333661 TI - The medico historical perspective of vitiligo (Switra). AB - The history of Switra is as old as the human civilization. The earliest medical literature has given the description of Switra in rgaveda and Atharvaveda. Switra is also narrated in Mahabharat and in Vinayapitika. A Roman physician known as Celsus first introduced the term Vitiligo in the second century A.D. Vitiligo is also known as Leucoderma. The history of psychosocial repercussion was described in Vedic literature and it is also found in our society. A population-based study was presented to understand the social implication of this disease. The detailed description of etiological factors and modalities of treatment is found in all ayurvedic classics. Bakuci (Psoralia cordifolia) is still continuing as a photosensitizing drug in the treatment of Switra from the time of Caraka. PMID- 17333662 TI - Sarangadhara--his contribution in Ayurvedic literature. AB - Sarangadhara was an erudite scholar who wrote the famous Sarangadharasamhita. It is the earliest Indian medical treatise to mention nadipariksa as a method of diagnosing the diseases. This classic treatise is also important for several other reasons, which can be deduced from its inclusion in the minor triad of authoritative works called Laghutrayi. The Samhita is designed to serve as a practitioner's handbook as the author himself states at the end of the work. The particulars of the author Sarangadhara are not known, apart from his name mentioned in one of the introductory verses and at the end of the work as the son of Damodara. The period of Sarangadhara can be fixed probably to the early part of 14th century A.D. PMID- 17333663 TI - History of Manuscriptology: study of medical manuscripts. AB - Connoisseurs of different areas of learning are apt to hold their particular area higher above all else, as the 'Science of Sciences'. These sciences transmitted to a scholar or to a common man are known through the texts, which are either handwritten or printed. The marvel of accuracy with which the vast literature specially Vedic literature has been handed down or transmitted to us orally, from generation to generations in India carried from person to person through mouth and ear, is a matter of great admiration all early literature that is now available in printed form, originally hand written i. e. in the form of manuscripts is the basis for the learning of science and technology today. Hence, it is forced to grant a top place of honor to the science of Manuscriptology and can be considered as 'Science of Sciences'. The scripts; Writing tools; Languages; Conservation, Preservation, Maintenance of the manuscripts; the study of medical manuscripts and its constraints; the strategies to validate the old concepts, drugs, diseases, and methods of treatment hidden in the manuscripts and knowledge application in the medical science are discussed here under. PMID- 17333664 TI - Bhisaksudharnavam--an unexplored precious Andhrasampradaya Ayurveda Grantha. AB - In India many Ayurvedic books were written in regional languages like Telugu, Bengali, Orissa, Gujarati etc. Though some of them are very useful, due to lack of maintenance and improper protection many of them became extinct and some of them are on the verge of extinction. Bhisaksudharnavam is one among such books, which is on the verge of extinction, details of which are presented here. PMID- 17333665 TI - Basic principles of pharmaceutical science in Ayurveda. AB - Pharmaceutical is one of the allied branches of science, which is closely associated with Medical science. Today pharmaceutical chemistry and pharmacognosy are playing important role in treatment for a disease and its prevention. Herbal medicines are being used by about 80% of the world population mostly in the developing countries in the primary health care. There has been an upsurge in demand for the Phyto-pharmaceutical products of Ayurveda in western nations, because of the fact that the synthetic drugs are considered to be unsafe. Due to this many national and multinational pharmaceutical companies are now concentrating on manufacturing of Ayurvedic Phyto-pharmaceutical products. Ayurveda is the Indian traditional system of medicine, which also deals about pharmaceutical science. The Ayurvedic knowledge of the pharmaceutical science is scattered in Ayurvedic classical texts. Saranghadhara Samhita, which is written by Saranghadhara, explain systematically about the information of the Ayurvedic pharmaceutical science and also updated it. Industrialized manufacturing of Ayurvedic dosage forms has brought in new challenges like deviation from basic concepts of medicine preparation. Saranghadhara Samrhita the devout text on pharmaceutics in Ayurveda comes handy to solve such problems, as the methods described are very lucid and easy to follow. PMID- 17333666 TI - Some explorative information regarding 'Jwaratimirabhaskara' and its author Kayastha Camunda. AB - Out of the treasure of Ayurvedic literature, a few texts have come in to lime light while some are in dark and available in incomplete form. But many names of the texts with unknown or known authors have been quoted by different subsequent authors in their texts or in the explications by their commentators, for which complete texts are not available at present. Among the texts on specific diseases, one notable work is 'Jwaratimirabhaskara' written by Kayastha Camunda. Nowhere a detailed account of author's identity, time and place has been mentioned, while short references are available in some historical books. However, manuscripts of this text are available in many repositories of our country. In this article, an attempt has been made to establish the identity of the author, period of the text and also to highlight the salient features of this text. PMID- 17333667 TI - Biography of Kasyapa and his contribution to Kaumarabhrtya (paediatrics). AB - Maharsi Kasyapa, the author of Kasyapa Samhita was the son of sage Marica and Kala. Kasyapa was an eminent physician and specialist in Kaumarabhrtya (children's diseases) during ancient times. He was contemporary with Punarvasu. Bower's manuscript referred to him as skillful in children's diseases and many formulae are ascribed to him. Two names Kasyapa and Kasyapa appear in the history. Hornle thinks these two are the names of the same rsi there is a confusion over his date. Vrddha Jivaka was his disciple. Kasyapa Samhita or Vrddha Jivakiya Samhita was composed in the form of dialogue between Kasyapa as the teacher and Vrddha Jivaka as his pupil. Vatsya later redacted it during Gupta period. The present editions of the Kasyapa Samhita are based on the manuscript acquired by Pandit Hemraj Sharma. First edition was published in 1953. This Samhita mainly deals with the children's diseases. PMID- 17333668 TI - Biography of Madhavakara: his scholarly contribution. AB - Madhavakara, the author of renowned work on 'Nidana-Rogaviniscaya', popularly known as Madhava Nidana. It may be the first or earliest compendium detailed description of the diseases based on Nidana Pancakam (Five groups of subjects concerned to aetio-pathogenesis). He was the son of Indukara according to the colophon of a manuscript of Vacaspati's commentary on Madhava Nidana. He is probably lived between 700-800 A.D., because he is quoted by Vrnda, who belongs to 8th century A.D. The book Madhava Nidana was translated in to Arabic as evidenced by the writings of Ali Ibn Sahl 849-850 A.D. and other Arabic authors. Hence, he probably lived between 700-800 A.D. Madhava Nidana is a popular work on Nidana (aetiopathogenesis) and it is the best in the field of ayurveda. "Nidane Madhavam srestah" and it is popularly known by the name of the author, but the title of the work is "Rugviniscaya" or "Rogaviniscaya". The subject matter explained in 73 chapters. The 1st chapter deals with Nidanapancakam and the other chapter's deals with diseases. The major contribution of Madhava is the new order of arranging diseases, description of new diseases and recognizing some disorders as independent diseases. The other works attributed to Madhava are Madhavacikitsa, Paryayaratnamala etc. The important commentaries on Madhavanidana are "Madhukosa" by Vijayaraksita and Srikanthadatta and "Atankadarpana" by Vidyavacaspati. The work is translated into English, Italian, Hindi, Bengali, Telugu etc., including some regional languages of India. PMID- 17333669 TI - Ayurveda gleaned through Buddhism. AB - The Pali canon consists of three Pitakas (baskets), which replete the Buddhism and is known as Tripitaka, viz, Vinaya, Sutta and Abhidhamma Pitakas. The original phase of Tripitaka (Buddhisim started in 544 B.C. and lastly systematized up to 29 B.C. The Buddhist literature also possesses the esoteric material of Medical Science, which is practiced and conserved in India since centuries. It refers to the fundamentals of medicine, rules of good living, which lay considerable emphasis on the hygiene of body, mind. Internal Medicine, curative medicine including symptoms, methods of diagnosis, theories of causation, materia-medica, therapeutics and treatment and skills of Jivaka. Some famous and popular prescriptions are also dealt with. PMID- 17333670 TI - Ayurvedic approach to pathya (ideal diet planning)--an appraisal. AB - Most health problems develop due to the wrong eating habits and cooking methods. Ayurveda deals with the pathya, apathya or pathya vyavastha (planning of diet- dietetics) in a very scientific and holistic way of Dietetics. The diet planning mentioned in our classical literature is very rational and based on certain principles. Lot of importance is given to the diet with regard to its processing, quality, quantity and so on. Due consideration is given to the atmosphere, psychological condition, status of health, digestion etc. of the person while dealing with this issue. The diet should also be planned according to the age, season, habitat and the preference of the person. In this paper the fundamental principals of Pathya vyavastha (dietetics) with appropriate references, recommended diet based on the texts and clinical findings for some important diseases such as diabetes, liver diseases, acid -peptic disorders, cardiac diseases are dealt with. The proper incorporation of diet not only can prevent many preventable disorders but plays major role in the management of the Diseases. Ayurveda has very holistic and scientific approach in planning the diet. The fundamental principles like tridosa, prakrti, the tastes, processing of food, the quality, quantity, and the rules regarding eating food if considered while incorporating the diet one can keep away from many diseases of body and mind. PMID- 17333671 TI - The blood of the insane. AB - The history of serological investigations of the blood of the insane is traced from the initial such study in 1854 by a solitary Scottish asylum physician, who counted the blood cells of his lunatic patients under a weak microscope, to the January 2005 announcement by an international team of geneticists of the development of a genomic blood test that can differentially diagnose schizophrenia and bipolar disorder. The story of the first claim of the development of a blood test for madness in 1912--the Abderhalden defensive ferments reaction test--is related in detail. Studies of the blood of the insane have followed four general methodological paradigms: the corpuscular richness paradigm (1854); the metabolic paradigm (c. 1895); the immunoserodiagnostic paradigm (1906); and the medical genomics paradigm (2005). PMID- 17333672 TI - Psychopathology and the essence of language: the interpretation of aphasia by Kurt Goldstein and Roman Jakobson. AB - This paper presents a comparative analysis of the research on aphasia carried out by the linguist Roman Jakobson and the neuropsychiatrist Kurt Goldstein. The linguistic theory of aphasia advocated by Jakobson in the 1950s and 1960s is based on clinical case studies reported by Goldstein at the beginning of the 1930s. However, Jakobson used Goldstein's clinical observations without taking into account his theoretical work on language pathology. In particular, Jakobson fed the symptoms described by Goldstein into a structuralist model, allowing him to predict different types of aphasia deductively. Goldstein, however, saw the clinical manifestations of aphasia as a particular way of being in the world. By studying the changes associated with the patient's reaction to the disease, Goldstein wanted to reach an understanding of language functioning in the normal subject. He distinguished between an instrumental use and a symbolic use of language, the latter mainly characteristic of language use in the normal subject. Only a symbolic use reveals the essence of language by showing its intimate nature, the psychic link tying the subject to the world. PMID- 17333673 TI - Behaviorally-based disorders: the historical social construction of youths' most prevalent psychiatric diagnoses. AB - Psychiatry in the USA controls the definitions of mental health disorders and diagnosis through required practice utilization of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and fiscal reimbursement using it. The present sociohistorical research paper presents and critically examines the Manual's systemic and diagnostic development of today's most prevalent youth mental health diagnoses (conduct and oppositional defiant disorders). Through a social construction theoretical paradigm, this research identified diagnostic classification systems, nosology changes, critical time periods, conducive social and cultural conditions, and key individuals involved in the development of these youth behaviorally-based disorders within two distinct historical time frames: 1880 to 1968 and 1969 to 2000. It also identified patterns of nosology system and diagnostic category changes based upon very limited empiricism, inordinately influenced by a limited number of individuals, and understood through a socially constructed framework. PMID- 17333674 TI - Hysteria and catatonia as motor disorders in historical context. AB - It is difficult to imagine motor symptoms in psychiatry as different as hysteria and catatonia. The mechanism of hysteria is presumed to be psychogenic, while catatonia has always been considered to be among the most organic syndromes in psychiatry. Yet hysteria and catatonia have historically been regarded as allied conditions, an observation borne out by recent developments in neuroscience as well as by a growing awareness that the presentation of both conditions has changed over the years. In hysteria, the main shift has been from motor symptoms to sensory complaints such as chronic fatigue; in catatonia, the major change has been the virtual disappearance of negativistic or oppositional behaviour. It is possible that catatonia as well as hysteria may be responsive to changing cultural norms. PMID- 17333675 TI - 'Mind in general' by Sir Alexander Crichton. AB - The history of the 'philosophies of psychiatry' can be defined as the contextualized study of past theoretical views on the nature, understanding and management of madness and related notions. The application of an hermeneutic apparatus to past psychiatric narratives gives rise to the history of psychiatry; its application to current narrative gives origin to the philosophy of psychiatry. If the latter employs off-the-shelf, ready-made, external philosophies, it follows a centripetal approach; if it starts from the inside of psychiatry and generates its own tools and meta-language, it follows a centrifugal approach. Psychiatry is burdened by intrinsic and extrinsic philosophical problems. The former result from its hybrid nature, i.e., from the fact that psychiatry unsteadily straddles the natural and human sciences. The latter are borrowed from the conceptual frames into which psychiatry has been inscribed since the 19th century. The philosophy of psychiatry may anticipate or follow empirical research. The ante rem mode is based on the idea that empirical research requires conceptual supervision, audit and guidance, for it is always ideology- and theory-laden. The post rem mode is based on the view that science is the only way to 'truth' and hence all that the philosophy of psychiatry can (or should) do is facilitate, interpret, justify, defend or glorify empirical findings. The Classic Text that follows was written by Sir Alexander Crichton at the end of the 18th century, and is a good example of the centripetal mode of philosophy-making. PMID- 17333676 TI - [Environmental epidemiology: shall we draw boundaries?]. PMID- 17333677 TI - [Health and environment: collaboration is needed]. PMID- 17333678 TI - [A forum on how to perform research in small areas]. PMID- 17333679 TI - [Italian association of epidemiology: starting from Sicily]. PMID- 17333680 TI - [Anti-smoking legislation: its effects and new challenges]. PMID- 17333681 TI - [Mortality after the 2003 invasion of Iraq: a cross sectional cluster sample survey]. PMID- 17333682 TI - [The SFUMA Project in Naples]. PMID- 17333683 TI - [Luxottica: a smoke free factory]. PMID- 17333684 TI - [Smoke: Irish flags in Washington]. PMID- 17333685 TI - [In Paris to debate on environmental epidemiology, September 2-6, 2006, Annual International Conference]. PMID- 17333687 TI - [A comparison between indoor air quality before and after the implementation of the smoking ban in public places in Italy]. AB - OBJECTIVE: To monitor indoor air quality index in a few Italian hospitality industry venues before and after the implementation of the smoking ban in January 2005. DESIGN: Indoor PM2.5 measurements were carried out in four Milan restaurants during evening hours in the period January-February 2004, and again in January-February 2005, with concurrent outdoor PM2.5 monitoring. The measures were recorded with a portable laser-operated aerosol analyzer with a sampling time of 2 minutes, calibrated by comparison with gravimetric method RESULTS: PM2.5 ranged between 187+/-52 and 709+/-180 mg/m3, and between 24+/-10 e 141+/-28 mg/m3 (p <0.0001) in the years 2004 and 2005, respectively. After the 2005 smoking ban, overall indoor fine particle pollution decreased by values in the range from 81 to 96%. CONCLUSIONS: Within the limits of a small sample, the study showed a good compliance with the smoking ban in the hospitality industry which resulted in a remarkable improvement in air quality index. Smoking ban thus appears to achieve the aims of protecting people from exposure to an unwanted dangerous pollutant such as environmental tobacco smoke. PMID- 17333686 TI - [Changes in PM10 and PM2.5 air levels in bars after the enforcement of the smoking ban in the Italian legislation]. AB - OBJECTIVE: in Italy law n.3/2003 has banned smoking in closed places, with the exception of private venues and of public venues reserved for smokers and marked as such. The present report estimates the effects of the ban. DESIGN: comparison between periods (before-after enforcement of the law). SETTING: City of Trieste. PARTICIPANTS: Six bars and four shops (convenience sample). MAIN OUTCOME MEASURES: particulate matter fractions PM10 and PM2.5 in bars and stores before and after enforcement of the law, outdoor PM10. Concentrations were estimated over the normal working hours of the premises. RESULTS: after enforcement of the law the concentration of PM2.5 in bars fell by 73% (p < 0.01), whereas the concentration of the PM10-2.5 fraction did not decrease significantly. Overall, the mean concentration of PM2.5 and PM10-2.5 in shops showed no statistically significant change. CONCLUSION: mean hourly PM2.5 concentrations, used as a proxy for indoor pollution caused by environmental tobacco smoke in bars were significantly reduced. PMID- 17333688 TI - [Exposure to passive smoking in local health units of northern Italy before and after the enforcement of the smoking ban]. AB - OBJECTIVE: to assess smoking habits, environmental tobacco smoke (ETS) exposure and smoking attitudes of workers toward different possible institutional restrictions before and after the implementation of the new Italian legislation about the public health protection from passive smoking (L 3/2003). DESIGN: Descriptive study based on self-reported questionnaires (2004 and 2005) and indoor measurement of particulate matter (PM, 2004 and 2006). SETTING: Local health authority n.1 Triestina (1,067 employees). PARTICIPANTS: 746 workers in 2004, 200 workers in 2005. MAIN OUTCOME MEASURE: percentage of smokers and opinions about different firms of control of smoking (absolute prohibition, smokers' reserved locals). Indoor mean levels of PM2.5 and PM10 in workplaces. RESULTS: smoking employees in 2004 and in 2005 were 28% and 31% (difference non statistically significant). Employees exposed to ETS has been reported decreased from 58% to 47% (p= 0.006). Major reduction has been reported in the offices, while exposure in examination rooms resulted higher in comparison to the offices, both in 2004 and in 2006 Among smokers 43% are available to external helps in order to quit or reduce smoking. Levels of PM2.5 were, in 2006, constantly smaller then those measured in 2004. The same for PM10 (a less specific tobacco smoke indicator) except for the value recorded in one room, slightly higher then in 2004. CONCLUSION: Our results confirm that ETS in the surveyed Local Health Authority has been reduced but not eliminated. It is necessary to implement further interventions finalized to defend health of not smoking people: a greater respect of the law, specific health promotion campaigns and free therapeutic interventions in workplaces. PMID- 17333689 TI - [Survey among GP's about their smoking habits, opinions and behaviours in smoking prevention in Lombardy (Northern Italy)]. AB - OBJECTIVE: to analyze smoking habits, opinions on smoking, curriculum and smoking prevention activities carried out by general practitioners in the Lombardy Region (Northern Italy). DESIGN AND PARTICIPANTS: between 2000 and 2002 a questionnaire about tobacco smoke retrieved from the European Project "GPs Empowerment" has been sent to 5348 general practitioners in the Lombardy Region. The questionnaire focuses on the difference of opinions and activity between smoking and non smoking physicians. We analyzed 3571 questionnaires voluntarily filled. RESULTS: The prevalence of smokers among the general practitioners in the Lombardy Region was 22.3% (CI95% 21-24%), (M: 24.2%, CI 95% 22-26% and F: 17.8%, CI 95% 15-20%). Physicians could play a role in the prevention of tobacco: 98.7% (CI 95% 98-99%) agree about the effectiveness of counseling but only 65.6% (CI95% 64-67%) regularly counsel their patients about smoking-related diseases and quitting. In this paper, we estimated that 963% (CI95% 96-97%) non smoking GPs consider counseling useful for their patients vs 92.6% (CI 95% 91-94%) of smoking physicians (p <0. 001); GPs who think to represent a model for people are more frequent among non smokers (97.5%, CI95% 97-98% vs 89.3%, CI 95% 87-91%;p <0.001). Those who discuss with their patients about tobacco addiction and cessation are 68.9% (CI95% 67-71%) among non smokers vs 53.4% (CI 95% 50-54%) among smokers (p <0.001). Finally 67% (CI 95 % 65-69%) interviewed physicians lacked a specific training in smoking prevention. Among them, 87.4%(CI 95% 86 89%) would attend the courses. CONCLUSION: this finding could be useful for planning or enhancing activities aimed at improving preventive and cessation methods. PMID- 17333690 TI - [Second-hand smoke exposure in Florence and Belluno before and after the Italian smoke-free legislation]. AB - INTRODUCTION: a law banning smoking in enclosed public places entered into force in Italy on January 10th 2005. OBJECTIVE: to compare the SHS exposure before and after the coming into force of the new anti-smoking law, with direct measurements in public venues and workplaces. METHODS: vapour-phase nicotine was measured using passive samplers, with personal and environmental sampling. SETTING: samples were collected in 10 municipality offices, 10 industry buildings and 11 public venues (4 discos and 7 pubs) in two towns (Florence and Belluno) from november 2004 to march 2005. RESULTS: during the pre-ban period a wide range of nicotine concentrations was observed. Offices and industry sector exhibited very low concentrations, 0,47 e 0,40 microg/m3 in median, respectively. Highest concentrations were measured in pubs and discos (35,59 and 127,16 microg/m3). After the smoking ban, a noteworthy reduction in nicotine concentrations was found with a stronger effect in pubs and discos (95% of decrease). DISCUSSION: the introduction of a national smoking ban led to a clear reduction in SHS exposure, with stronger results in environments less protected by previous regulations. PMID- 17333691 TI - [An index of socioeconomic position based on 2001 Census, Rome]. AB - OBJECTIVE: to develop an index of socioeconomic position based on the 2001 Census to characterise the census blocks in Rome. DESIGN AND SETTING: we considered the 4888 census blocks in Rome with at least 50 inhabitants (average population: 500 people). We considered census information that represented various dimensions of deprivation: education, occupation, housing tenure, family composition and immigration. We performed a factorial analysis, and created a composite index of socioeconomic position. We considered the quintiles of the distribution of census block in order to have a 5-level indicator. PARTICIPANTS: 2516666 subjects who were residents in Rome in October, 2001. RESULTS: four factors explained 84% of the variance. The first factor combined education, occupation and crowding and explained 49.5% of the variance. The second (14% of variance) represented immigration, the third (11.3%) family composition, and the fourth (9.1%) home ownership. High-level census blocks tended to have older residents, a higher employment rate, more students and retirees, and fewer part time employed residents than low census blocks. CONCLUSION: when individual measures of socioeconomic position are missing, small area indicators based on census data can be used as a proxy of individual indices. In addition, they describe all socioeconomic aspects of the area. This study provides an instrument that can be used in public health and epidemiology to evaluate socioeconomic differences in health. PMID- 17333692 TI - [Asbestos fibre dimensions and mesothelioma]. AB - The critical considerations formulated by Tomatis et al. did not take into account all the experimental works and all the research on human pleura that from the Seventies on has unanimously indicated that asbestos fibre mesothelioma is caused by the ultrafine fibres class. These fibres that are so fine are not visible with light microscopy are mostly ultrashort, but they also include, in varying percentages, elements that are >5 microm long. The conclusions of Tomatis et al, which attribute mesothelioma to fibres of all lengths and diameters, are not confirmed in the literature. Today, mesothelioma prevention must consist of identifying and cutting down airborne ultrafine fibres, above all in urban environments. The techniques for doing so now exist and can be applied. The ultrafine class of asbestos, forgotten for decades, must be the principal target for prevention programs and must be widely monitored in work and daily life settings. PMID- 17333693 TI - [Communicating the quality of research to the epidemiologists: the risks of misinformation]. PMID- 17333694 TI - [The risks of no information]. PMID- 17333695 TI - [Effective laws for tobacco control: EU directives and Italian legislation]. AB - Effective tobacco control policies include law issuing: bans/restrictions on smoking in public areas and workplaces, increasing of taxes on tobacco products, bans on advertising of tobacco products, warning labels on cigarette boxes. For some of these policies the European Union (EU) has introduced specific directives that EU member states have to put into law. This paper briefly presents literature data, EU directives and the laws consequently issued in Italy. The importance of standardizing European legislation, especially for those policies that are not enforced by EU directives is also discussed. In Italy and in some other European countries smoking is forbidden in public and work-places, despite no EU directive. The positive impact of this ban in these countries suggests that it should be considered a priority in the European policies against tobacco in order to reduce the gap between literature recommendations and actions. PMID- 17333701 TI - [Effect of health education on the diabetic patient]. PMID- 17333702 TI - [Pain and wounds]. PMID- 17333703 TI - [For a better management of pain in patients with wounds]. PMID- 17333704 TI - [Chronic wounds and pain]. PMID- 17333705 TI - [Pain and dressings]. PMID- 17333706 TI - [Painful care and analgesia]. PMID- 17333707 TI - [General anesthesia care in the patient's room]. PMID- 17333708 TI - [Pain from complex dressing changes in terminal care]. PMID- 17333709 TI - [Bibliography. Pain and wounds]. PMID- 17333710 TI - [1/10 History of hygiene]. PMID- 17333711 TI - [1/10 Education in emergency care]. PMID- 17333712 TI - [1/3 Non-steroidal anti-inflammatory drugs]. PMID- 17333713 TI - [20th century Galileo? The significance of Freud's life and work, seen in terms of the history of science (lecture on May 6th, 2006)]. AB - This paper gives a sketch of Freud's life and work, discusses the difficulties of reception he met, and, referring to the well-known statement that psychoanalysis represents the third blow to the narcissism of mankind, maintains that, in terms of the history of science, a more meaningful parallel can be drawn between Freud and Galileo than between Freud and Copernicus or Darwin. PMID- 17333714 TI - [Shadows of Freiberg. Was Julius Freud born in Roznau?]. AB - This article refers to the marked influence which Freud's brother Julius, who died at an early age, exercised upon the character of little Sigmund. The uncertainties hovering around his figure start with the question of the place and date of his birth. Was he born in Roznau instead of Freiberg as usually is assumed? The Freud family tradition and certain convictions of earlier biographers of Freud provide some good reasons to believe so. PMID- 17333715 TI - [The moving sidewalk, 1900]. AB - Two photos of the same scene, but taken at an interval of a second or two, raise questions of the time lapse and what occurs between frozen frames. The subjects are Freud and a group of his relatives in the summer of 1900. As if waiting for a lecture which has not yet begun, and may never begin, they face their respective fates and futures. What will happen is implicit in what is happening and in what has already happened. The mechanisms of the Trottoir roulant or of dream scenes recalled are analogous to the experience of time reconstructed from these fragmented images. PMID- 17333716 TI - [Electra "ancient and modern". An evening of the Wednesday Society in 1905 (with an unpublished postcard from Freud to Paul Federn)]. AB - A postcard that Freud sent to Paul Federn on May 18, 1905, documents a meeting of the Wednesday Society devoted to Sophocles' Electra and to the controversial adaptation by Hugo von Hofmannsthal. The debate surrounding Hofmannsthal's play had already ignited on the occasion of its world premiere in Berlin in October 1903. Freud and the other members of the Wednesday group would have gathered first impressions from the predominantly negative theater reviews in Berlin newspapers and, above all, in a hostile pan of the play published in the influential Viennese daily Neue Freie Presse. As late as the summer of 1904 essays appeared in prominent journals such as Die Fackel and Die Zukunft, in which Electra was defended and praised, alternately, as a character embodying radical sublimation or as a modern hysteric based on the findings of Breuer and Freud. A statement of Freud's, made in 1909, suggests that the outcome of the 1905 discussion had been a negative one. The few traces of the Electra myth in Freud's later remarks and publications point to productive resistance that contributed in the years 1907-1910 to a firmer theoretical grounding of the Oedipus complex. PMID- 17333717 TI - [A summer afternoon in Grinzing. Thomas Mann visits Sigmund Freud]. AB - Focussing on June 14th, 1936 when Mann visited Freud to read him the speech he had delivered in Vienna in celebration of Freud's 80th birthday, the paper investigates the "less than simple" relation between the two men. It shows how they gradually approached each other and then in 1929 entered into direct contact after Mann had publicly underlined Freud's relevance for his project "psychology and myth". Some traces of personal ambivalence contained in the 1936 lecture are highlighted. The author discusses the potential significance for both men of Freud's response to Mann's speech where he interpreted aspects of Napoleon's life as based on his identification with the biblical Joseph in order to surpass his elder brother. Finally it is considered whether Mann's contact with Freud may have helped him to cope with the trauma of the early loss of his father. PMID- 17333718 TI - [An offspring of love. Freud on belief]. AB - This paper elucidates Freud's ideas of belief and believing. By investigating the semantic field, it discusses the place of his theory of religion in the context of his thought. It argues for a consistent model which does not stem from antireligious prejudice but meshes with his whole thinking. For Freud religious belief was a special case of the general attitude of believing. He situated it within a three-stage development of the individual as well as of humanity, starting with a state of magical-animistic thinking in autoerotism and narcissism and leading, via object-dependency and a belief in omnipotent parental figures, to emancipation through rationality and critical judgement. The origin of belief in wishing accounts for the believer's lack of judgement and submission to religious authorities. In the end some of the advantages and disadvantages of Freud's model are highlighted. PMID- 17333719 TI - [A comment on Max Eitingon's address at the session held by the Chewrah Psychoanalytith b'Erez-Israel in Jerusalem on May 6th, 1939]. AB - The paper sketches the context of Eitingon's address in celebration of Freud's 83rd birthday (which follows hereafter), especially regarding the recent publication of Freud's book on Moses which Erich Gumbel presented with great care on this occasion. PMID- 17333720 TI - [Freud's 83 birthday. Geburtstag, May 6, 1939]. PMID- 17333721 TI - [Freud in the journals of the German speaking exile]. AB - Freud and psychoanalysis figure frequently in exile journals. This paper documents two letters to the editor written by Alexander Freud who denied that his brother Sigmund had been a zionist, and the recollections of the sculptor Konigsberger who had made a bust of Freud in 1920. PMID- 17333722 TI - ["Dear Papa!"--"My dear Anna": exchange of letters between Freud and his youngest daughter]. PMID- 17333723 TI - Severity of Malaria cases reported in urban and rural hospitals in Malaysia. AB - The age distribution, types of infection and clinical patterns of malaria were compared in patients admitted to an urban and a rural hospital. Analysis of the cases seen in urban setting characteristically indicated a relatively low transmission rate of the disease, whereas the mean inoculation rate in patients from the rural hospital was found to be at least twenty folds higher. Plasmodium vivax was the predominant causative species in the urban hospital (p = 0.01), infecting mostly adult (p = 0.001) males (p = 0.01). The geometric mean parasite count at 3432/microl among the urban patients was significantly higher than that in the rural patients at 1422/microl (p = 0.04). Coma and death were more common among the cases seen in the urban hospital (p = 0.003), while severe anemia was the significant complication in the rural setting. Overall, the provisional diagnosis of malaria was relatively low in the urban hospital (p = 0.02). The results from this study highlighted the need to define the extent of malaria in urban areas. This report attempts to identify the non-climatic determinants of the infection and, furthermore, to provide a more informed basis to describe the burden of the disease. PMID- 17333724 TI - Artesunate and a major metabolite, dihydroartemisinin, diminish mitogen-induced lymphocyte proliferation and activation. AB - Artemisinin derivatives are potent antimalarial compounds that may have immunomodulatory properties. Artesunate (range 0.01-2 mirog/ml) or dihydroartemisinin (range 0.01-8 microg/ml; DHART) were added to peripheral blood mononuclear cells (PBMC) or whole blood (WB) cultures before or simultaneously upon stimulation with phytohemagglutinin (PHA), a T cell mitogen. Lymphoproliferation was then measured by 3[H]-thymidine incorporation, and CD4+ and CD8+ T cell activation was assessed by expression of CD69 or CD25 using flow cytometry. Reverse transcriptase polymerase chain reaction depicted PBMC mRNA production for interleukins 2, 4, 12, and 15, interferon-gamma, and tumor necrosis factor-alpha. Artesunate concentrations between 0.1-1.5 microg/ml reduced lymphoproliferation in PHA-stimulated PBMC and WB cultures in a generally dose-dependent manner; inhibition by DHART was similar. Removing artesunate from PBMC before PHA was added abolished the reduction. PBMCs cultured with artesunate or DHART simultaneously with PHA showed modestly reduced proportions of CD4+ and CD8+ T cells expressing CD69 and CD25. Artesunate had little effect on qualitative cytokine mRNA levels in PHA-stimulated PBMC cultures. Artesunate and DHART may diminish some PBMC responses to immunologic stimuli. Further work is warranted to define the mechanisms involved, and whether this affects malaria treatment. PMID- 17333725 TI - High-performance liquid chromatographic method for the determination of ivermectin in plasma. AB - A simple, sensitive, selective and reproducible method based on reversed-phase chromatography was developed for the determination of ivermectin in human plasma. The internal standard (moxidectin) was separated from ivermectin on a Hypersil Gold C18 column (150 x 4.6 mm, 5 microm particle size), with retention time of 3.7 and 7.0 minutes, respectively. Fluorescence detection was set at an excitation and emission wavelength of 365 and 475 nm, respectively. The mobile phase consisted of acetonitrile, methanol and distilled water (50:45:5, v/v/v), running through the column at a flow rate of 1.5 ml/minute. The chromatographic analysis was operated at 25 degrees C. Sample preparation (100 microl plasma) was done by a single step protein precipitation with acetonitrile, followed by derivatization with 100 microl of N-methylimidazole solution in acetonitrile (1:1, v/v) and 150 microl of trifluoroacetic anhydrous solution in acetonitrile (1:2, v/v). Calibration curve over the concentration range of 20-8000 ng/ml plasma was linear with correlation coefficient better than 0.995. The precision of the method based on within-day repeatability and reproducibility (day-to-day variation) was below 15% (coefficient of variation) Good accuracy was observed for both intra-day and inter-day assays, as indicated by the minimal deviation of mean values found with measured samples from that of the theoretical values (below +15%). Limit of quantification was 0.02 ng using 100 microl sample. The mean recovery for ivermectin and the internal standard was greater than 90%. The method was free from interference from endogenous substances and commonly used drugs. The method appears to be robust and has been applied to the investigation of plasma concentration vs time profile of ivermectin in five healthy Thai volunteers following a single oral dose of 200 microg ivermectin/kg body weight. PMID- 17333726 TI - Intestinal parasites in school-aged children in villages bordering Tonle Sap Lake, Cambodia. AB - The objective of this study was to study Schistosoma mekongi and other intestinal parasitic infections, and intestinal symptoms and related complaints among school age children and adolescents living around Tonle Sap Lake. Villages were selected where there were potential signs of schistosomiasis (hepatomegaly), and where subjects complained of intestinal symptoms. Stool samples were collected from 1,616 children and were examined by Kato-Katz, SAF concentration, and Baermann technique; short clinical examinations were also performed. No S. mekongi infection was detected, although a high level of intense human water contacts was reported. Helminth infection such as Ascaris lumbricoides (27.7%) and hookworms (29.7%) were common. Trichuris trichiura 4.4%), Hymenolepis nana (6.2%), Giardia lamblia (4.2%), and Entamoeba spp (14.4%) were also recorded. Strongyloides stercoralis was frequently diagnosed (20.2%). It was concluded that it is unlikely that S. mekongi is transmitted in Tonle Sap Lake. However, other intestinal parasitic infections are widespread. In particular, S. stercoralis should be considered an important etiologic agent in children and adolescents with abdominal complaints. PMID- 17333727 TI - Intestinal helminth infections among reproductive age women in Vietnam: prevalence, co-infection and risk factors. AB - Intestinal helminth infections are a significant public health problem for Vietnamese women, but prevalence and risk factor data are scarce. The objectives of this paper were to (1) determine the prevalence of helminth infections among women; (2) investigate interactions among intestinal helminth species in individuals and (3) identify risk factors that contribute to intestinal helminth infections. In a nationwide survey conducted in 1995, 9550 households in 53 provinces were covered using a stratified two-stage cluster survey. Stool specimens were examined by Kato-Katz technique. Of 5,127 women, 76% were infected with one or more helminth species, 36% with hookworm, 59% with Ascaris lumbricoides and 28% with Trichuris trichiura. A. lumbricoides and T. trichiura were more likely to be concurrent than expected by chance. There was significant interaction between prevalence and intensity of infection in all three species. All three helminth species were more common in certain ecologic zones than others. Hookworm infection was associated with farming [Odd ratio (OR) = 2.1] and lack of a closed latrine (OR = 2.0), A. lumbricoides with use of untreated feces as fertilizer (OR = 1.2) and coinfection with T. trichiura (OR = 2.1) and T trichiura with A. lumbricoides co-infection (OR = 2.1). Our findings suggest that reproductive-age women, especially rural farmers, should be included among the high priority groups for helminth control programs through mass chemotherapy and improving sanitation. PMID- 17333728 TI - Risk factors for strongyloidiasis hyperinfection and clinical outcomes. AB - Strongyloidiasis, caused by Strongyloides stercoralis, consists of various clinical syndromes. Strongyloidiasis hyperinfection leads to morbidity and mortality particularly in immunocompromized patients. This study aimed to determine the risk factors for strongyloidiasis hyperinfection and clinical outcomes. The medical records for hospitalized patients infected with S. stercoralis at Ramathibodi Hospital during 1994-2005 were retrospectively reviewed. Risk factors for strongyloidiasis hyperinfection were determined. There were 123 episodes of strongyloidiasis in 111 patients. The mean age was 46.8 +/- 17.8 years; 61% were males. Of 123 episodes, 37 (30.1%) had strongyloidiasis hyperinfection; the others had chronic strongyloidiasis. All the patients with strongyloidiasis hyperinfection and 88.3% of those with chronic strongyloidiasis were immunocompromized (p = 0.032); 89.2% of the former and 55.8% of the latter had received corticosteroids (p < 0.001). There were no significant differences in the type of immunocompromized host and the corticosteroid dosage between the two groups (p > 0.05). The hyperinfection group had a lower mean serum protein (p = 0.026) and albumin (p = 0.027) but a higher frequency of sepsis (p = 0.029), asthma-like symptoms (p = 0.025), adult respiratory distress syndrome (p = 0.026), and a longer duration of treatment (p=0.004). By logistic regression, corticosteroids use was a risk factor for hyperinfection (OR = 6.5, 95% CI = 2.1 20.0, p = 0.001). Most of the patients were treated with albendazole or thiabendazole, with a cure rate of 76.9%, whereas other recent cases treated with ivermectin had an average cure rate of 83.3%. The overall mortality rate was 8.1%. PMID- 17333729 TI - Protective immunity elicited by ultraviolet-irradiated third-stage infective hookworm (Necator americanus and Ancylostoma caninum) larvae in mice and hamsters. AB - The protective immunity elicited by ultraviolet-irradiated third-stage infective larvae of Necator americanus (UV-NaL3) and Ancylostoma caninum (UV-AcL3) was evaluated in laboratory mice (a non-permissive model) and hamsters (a permissive model). After optimizing the time of exposure to UV-irradiation, both oral and subcutaneous vaccination routes with UV-AcL3 in mice were explored. Oral vaccination was more effective at reducing the number of challenge AcL3 entering the lungs, whereas subcutaneous vaccination was more effective at blocking muscle entry. When UV-irradiated NaL3 and non-irradiated AcL3 were used as vaccines in hamsters, both of them were effective at reducing adult hookworm burdens. However, the length of protection afforded by UV-irradiated L3 was substantially greater than that resulting from immunization with non-irradiated L3. A single dose was less effective than multiple doses. The protective immunity elicited by UV-irradiated NaL3 given once every other week for a total of three immunizations was similar to that elicited by non-irradiated AcL3 given during the same schedule. Protection was not significantly affected by administering the L3 on a weekly basis for a total of three immunizations, even though the antibody titers were reduced using this schedule. These studies will facilitate the elucidation of the mechanisms underlying larval protection. PMID- 17333730 TI - A second case of diphyllobothriasis in Malaysia. AB - Diphyllobothriasis was first reported in Malaysia in 2002. We are reporting a second case of diphyllobothriasis in Malaysia. The patient was a 37-year-old Chinese male seen at the outpatient clinic with a complaint of passing strands of white color flat worm in his stool. He had no other abdominal complaints. Laboratory and physical examinations were normal. Diphyllobothrium latum was confirmed by examination of the gravid proglottids passed out and the typical operculated eggs expelled from the ruptured proglottids. The patient had a history of eating raw fish. He was treated with a single dose of praziquantel. PMID- 17333731 TI - Silent transmission of virus during a Dengue epidemic, Nakhon Pathom Province, Thailand 2001. AB - In the year 2001 a large dengue fever (DF)/dengue hemorrhagic fever (DHF) outbreak occurred in Nakhon Pathom Province, Thailand. Three thousand one hundred twelve cases of DHF were reported, an attack rate of 393 per 100,000 population. The Nakhon Pathom Provincial Health Office immediately carried out a control action according to WHO recommendations. Active serological surveys and viral RNA isolation were carried out to detect silent transmission of dengue virus in 329 healthy volunteers in Nakhon Pathom Province subdistricts where the dengue epidemic had the highest rate of infection of 2.5 per 1000. Eight point eight percent of these volunteers had a serum sample positive for DF/DHF virus IgM antibody. The highest prevalence occurred in the 15 to 40 year old group. In two instances viral RNA was detected by PCR and dengue serotype 3 was subsequently identified. The data support the hypothesis of subclinical infection with dengue virus. This high frequency of virus circulation combined with a high population density, urbanization and increasing breeding sites for mosquitoes, needs to be taken into account in the evaluation of viral transmission during and after epidemics. This underlines the importance of community-based control in informing people of their involvement in virus transmission and the importance of personal protection. PMID- 17333732 TI - Viral investigation of acute hemorrhagic conjunctivitis outbreak (2003) in Nepal using molecular methods. AB - A nationwide outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Nepal during August to September 2003, which affected nearly half of the population. Sixty conjunctival swabs from AHC patients were collected at Tilganga Eye Center in Kathmandu. For the first time in Nepal, we demonstrated the etiologic viral agents of AHC, namely, Coxsackievirus A24 variant (CA24v) by reverse transcription real time polymerase chain reaction (PCR). Of the 60 samples, 19 were positive for CA24v. No difference in the two genders was observed. Conversely, Adenovirus (AdV) was detected in 32 samples, which suggested that the epidemic was caused by mixed infection. AdV was detected also on 10 rupee notes. Findings indicated that inadequate personal hygiene was the main cause of the spread of these highly contagious viruses in the community environment in Nepal during the summer of 2003. PMID- 17333733 TI - Purpuric-like rash as cutaneous eruptions in parvovirus B19 infection in Thai infant. AB - An 8-month-old girl presented with fever, rash, and diarrhea. Physical examination revealed multiple well-circumscribed, brownish-black, purpuric-like rashes on the face, arms, and legs with cervical and suboccipital lymphadenopathy. Laboratory findings showed mild anemia with thrombocytopenia and positive polymerase chain reaction for parvovirus 819 DNA in the serum. The patient recovered uneventfully with symptomatic and supportive treatment. Since the infection can manifest in many dermatological patterns, it should also be included in the differential diagnosis of febrile illness with purpuric rash in children. PMID- 17333734 TI - Repellency of essential oils extracted from plants in Thailand against four mosquito vectors (Diptera: Culicidae) and oviposition deterrent effects against Aedes aegypti (Diptera: Culicidae). AB - In this study we evaluated and reported repellent effects of essential oils from Thai plants against 4 mosquito vectors: Aedes aegypti, Ae. albopictus, Anopheles. dirus and Culex quinquefasciatus under laboratory conditions using human volunteers. The essential oils were extracted from 18 plant species, belonging to 11 families, and the oils were then prepared as 10% solution in absolute ethanol with additives. Two chemical repellents, deet and IR3535, were also prepared in the same formulation as the essential oil repellents and tested for repellency as controls. The essential oils were also evaluated for oviposition deterrent effects against Ae. aegypti under laboratory conditions. The results show night biting mosquitoes (An. dirus and Cx. quinquefasciatus) and Ae. albopictus were more sensitive to all the essential oils (repellency 4.5 - 8 hours) than was Ae. aegypti (repellency 0.3 - 2.8 hours), whereas deet and IR3535 provided excellent repellency against all four mosquito species (repellency 6.7- 8 hours). All essential oils exhibited oviposition deterrent activity against Ae. aegypti with various degrees of repellency ranging from 16.6 to 94.7%, whereas deet and IR3535 had no repellency. The present study demonstrates the potential for using essential oils as mosquito repellents and oviposition deterrents. These findings may lead to new and more effective strategies for protection from and control of mosquitoes. PMID- 17333735 TI - Abundance and distribution of Xenopsylla cheopis on small mammals collected in West Java, Indonesia during rodent-borne disease surveys. AB - During February 2004 and September 2005, Xenopsylla cheopis were collected from small mammal hosts during rodent-bone disease surveys in Jakarta and Bandung, Indonesia. During 4 trap nights in Jakarta, 4 rodent species (Rattus exulans, Rattus norvegicus, Rattus tanezumi and Mus musculus) and one shrew species (Suncus murinus) were collected. Rattus tanezumi had the highest X. cheopis load (128 X. cheopis from 84 R. tanezumi) but R. norvegicus had the highest flea index, 1.8. In Bandung, over 6 trap nights 3 rodent species were collected (R. norvegicus, R. tanezumi and M. musculus) and the shrew, S. murinus, were collected. Rattus norvegicus had the highest number of X. cheopis collected (407 X. cheopis from 181 R. norvegicus) but R. tanezumi had the highest flea index, 3.5. During both surveys, X. cheopis was the species of flea collected. PMID- 17333736 TI - The effect of green pit viper (Trimeresurus albolabris) venom on platelet morphology by electron microscopy. AB - The incidence of venomous snake bites increases every year in Thailand, especially due to green pit viper. After the bite, there is bleeding due to thrombin-like property of the venom. The mean platelet volume has been reported to be decreased in those who have been bitten by this snake. In this study we investigate the effect of green pit viper venom (Trimeresurus albolabris) on platelet volume (MPV), number and morphology of platelets in vitro. The test was carried out by washing platelets in phosphate buffer at pH 7.2 to remove fibrinogen, then the washed platelets were mixed with green pit viper venom. Platelet morphology was examined by scanning electron microscope (SEM). The morphology of platelets was smaller than normal which ranges from 1.1- 1.2 microm. Green pit viper venom can directly effect platelet morphology, decreasing platelet volume. PMID- 17333737 TI - Polymerase chain reaction for detection of Mycobacterium tuberculosis in papanicolaou-stained fine needle aspirated smears for diagnosis of cervical tuberculous lymphadenitis. AB - A polymerase chain reaction (PCR) protocol for detecting IS6110 repetitive insertion sequence of Mycobacterium tuberculosis (MTB) was tested on archival Papanicolaou (Pap)-stained fine needle aspirated (FNA) smears from 24 patients with cervical tuberculous lymphadenopathy and 30 negative controls. The protocol involved protease digestion or phenolchloroform extraction, and simple or nested PCR, with PCR amplification of human beta-globin gene for internal control of DNA quality. Sensitivity of 50% and specificity of 100% were obtained. Sensitivity in smears showing necrosis without granuloma was 70% (7/10), whereas it was 36% (5/14) in smears with presence of granuloma. On the other hand, sensitivity of 18% (4/22) was obtained using FNA acid-fast stain, 25% (1/4) for acid-fast stain in histological section, 50% (2/4) for culture, and 100% (8/8) for PCR of fresh specimens. PCR for MTB detection in Papanicolaou-stained slides is a practical and valuable method when no fresh specimen but only Pap-stained smear is available. PMID- 17333738 TI - Cerebrospinal fluid adenosine deaminase activity for the diagnosis of tuberculous meningitis in adults. AB - We studied adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of 16 cases of tuberculous meningitis, 4 cases of cryptococcal meningitis, 5 cases of bacterial meningitis, 12 cases of eosinophilic meningitis, 26 cases of aseptic meningitis, 6 cases of carcinomatous meningitis and 108 cases with normal CSF. The mean CSF ADA values for the different groups were: 39.44 +/- 41.46, 13.00 +/- 7.43, 34.20 +/- 40.81, 3.17 +/- 4.82, 10.03 +/- 9.23, 8.67 +/- 13.60, and 2.58 +/ 2.90 U/I, respectively. Comparing the ADA activity between patients with tuberculous meningitis and non-tuberculous meningitis, the receiver-operating characteristic (ROC) curve identified a CSF ADA level of 15.5 U/I as the best cut off value to differentiate between the two, with a sensitivity of 75% and a specificity of 93%, with an area under the curve of 0.92. When tuberculous meningitis was compared with aseptic and carcinomatous meningitis, the ROC curve identified a CSF ADA level of 19.0 U/I as the best cut-off value for differentiation, with a sensitivity of 69% and a specificity of 94%, with an area under the curve of 0.83. The level of CSF ADA may be useful as a complementary tool in the early diagnosis of tuberculous meningitis. PMID- 17333739 TI - Near miss diagnosis of childhood tuberculosis. AB - Tuberculosis (TB) remains a public health problem in Malaysia. We describe three atypical cases of serious tuberculosis in children. The potential diagnostic pitfall in these cases is highlighted by its unusual presentation in a setting of culture-negative infection. A positive polymerase chain reaction (PCR) in each case assists in gauging the diagnosis in concordance with appropriate clinical findings. PMID- 17333740 TI - Enzyme-linked immunosorbent assay for serodiagnosis of Helicobacter pylori in dyspeptic patients and volunteer blood donors. AB - Helicobacter pylori, an important etiological agent in the development of gastritis, peptic ulcer and gastric carcinoma, can be detected by the enzyme linked immunosorbent assay (ELISA). Our objectives were: (1) to evaluate the efficacy of a commercial ELISA kit (Pyloriset EIA-G III) in sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for diagnosis of H. pylori infection in Thai dyspeptic patients in Khon Kaen Thailand; and (2) to examine the seroprevalence of H. pylori among blood donors at Srinagarind Hospital's Blood Bank, Khon Kaen University, by the commercial ELISA. Gastric biopsies obtained from 137 dyspeptic patients were diagnosed by culture, rapid urease test (RUT) and histology. Serum samples from the same dyspeptic patients and 100 healthy blood donors were assayed using the commercial ELISA. H. pylori infection in dyspeptic patients was considered positive when the culture or both RUT and histology were positive. Using a cut off value at a titer of 20 U/ml (as recommended by the manufacturer), we found the commercial ELISA kit had a sensitivity of 93.3%, specificity of 75.3%, PPV of 74.7%, NPV of 93.5% and accuracy of 83.2%. The overall H. pylori seroprevalence in the healthy blood donors was 57%. Of the 100 healthy blood donors, 39 (60.9%) of the males and 18 (50.0%) of the females were seropositive. PMID- 17333741 TI - Evaluation of the motility indole urease (MIU) test to detect Helicobacter pylori infection. AB - The aim of this study was to evaluate the diagnostic value of the new motility indole urease (MIU) test and Campylobacter Like Organism (CLO) test with culture as the gold standard. This study were done on 225 biopsy samples from gastric antra taken from chronic dyspeptic patients from several hospitals in Jakarta. On the MIU test, the biopsy tissue sample was submerged in the MIU tube agar to a depth of about 2/3 from the surface, and incubated at room temperature. Another piece of biopsy tissue was used for CLO and cultured. The CLO and MIU tests were considered positive if the color changed from yellow to red, and were considered negative if there was no color change within 24 hours. The CLO test compared with culture had 75.9% sensitivity, 78.6% specificity, 76.6% positive predictive value and 78% negative predictive value, whereas the result of the MIU test compared with the culture method showed 96.3% sensitivity, 82.1% specificity, 83.2% positive predictive value, and 96% negative predictive value. The MIU test with its higher sensitivity and specificity may be used as an alternative diagnostic method for H. pylori infection. PMID- 17333742 TI - Patterns of Helicobacter pylori isolate resistance to fluoroquinolones, amoxicillin, clarithromycin and metronidazoles. AB - Helicobacter pylori eradication using the three antibiotic regimen of amoxicillin, clarithromycin and metronidazole often fails, making it imperative to find substitutes. The following study made use of 72 H. pylori isolates derived from pyloric antrum mucosa biopsies of gastritis and chronic dyspepsia patients treated at the Cipto Mangunkusumo National General Hospital and three private hospitals in Jakarta. Testing for H. pylori sensitivity to various antimicrobials was conducted using the disk diffusion method (Kirby Bauer) and procedures determined by the Clinical and Laboratory Standards Intitute (CLSI)/NCCLS. The resistance rates of the isolates were 100% for metronodazole, 27.8% for clarithromycin, 19.4% for amoxicillin, 6.9% for ciprofloxacin, norfloxacin and ofloxacin, 2.8% for sparfloxacin and gatifloxacin, and 1.4% for levofloxacin and moxifloxacin. Fluoroquinolons have the lowest resistance compared to amoxicillin, clarithromycin and metronidazole. PMID- 17333743 TI - Antenatal care providers' practices and opinions on the services of antenatal syphilis screening in Ulaanbaatar, Mongolia. AB - The objectives of this study were to review antenatal syphilis screening and to assess antenatal care providers' practices and opinions in Ulaanbaatar, Mongolia. A cross-sectional study on antenatal syphilis screening was conducted. The study settings were all 16 antenatal care clinics, and a random selection of 30 family units from six districts in Ulaanbaatar, Mongolia. Interviews were conducted with 150 antenatal care providers and 27 antenatal care heads/leaders. Antenatal syphilis screening in Ulaanbaatar was complex. Most pregnant women had antenatal care at family units or antenatal clinics, but syphilis blood testing could be performed only in some district general hospitals. Syphilis positive-screening cases were referred to the venereologists for confirmation of results, appropriate treatment, contact tracing, and follow-up. The providers agreed with the need for syphilis screening in pregnant women but identified as constraints the limited time for performing the screening due to late antenatal visit, women's lack of knowledge, poverty, and geographic barriers. The practice of providers varied, and the opinion on a one-stop service was positive. The main conclusions concerning the failure of universal antenatal syphilis screening were limited accessibility and feasibility of the service, and the ignorance of both women and providers on the importance of screening. It was agreed that decentralization of antenatal syphilis screening would improve the system. PMID- 17333744 TI - Enteropathogenic bacteria and enterotoxin-producing Staphylococcus aureus isolated from ready-to-eat foods in Khon Kaen, Thailand. AB - The objective of this study was to investigate the microbiological quality of ready-to-eat food in the Municipality of Khon Kaen, Thailand. Four categories of 186 food samples were collected: (1) high heat food; (2) low heat food; (3) no heat food; and, 4) on-site prepared fruit juices and beverages. Of the food samples, 145 (78%) failed to meet acceptable microbiological standards, including fruit juice and beverages (100%), no heat food (91.7%), low heat food (81.7%) and high heat food (57.9%). The most frequent bacterial indexes indicating unacceptability were the most probable number (MPN) of coliforms (78%), the bacterial colony count (58%), and the MPN of E. coli (46%). Pathogenic bacteria were found in 6.5% of food samples. Salmonella, Vibrio cholerae non O1 and Aeromonas hydrophila were found in 4.3, 1.6 and 0.5% of the total food samples, respectively. The serovars of Salmonella found in food were S. Derby, S. Give, S. Krefield, S. Paratyphi B, S. Verchow, S. Lexington and S. Senftenberg. Staphylococcus aureus concentrations of >10(2) CFU/g and >10(5) CFU/g were found in 10.8% and 1.1% of the food samples. Enterotoxin types AB and A of S. aureus were found in 2.7% of the food samples. These results indicate that more than half of the ready-to-eat foods tested in Khon Kaen municipality did not meet microbiological national standards and many kinds of enteropathogenic bacteria were found, suggesting food stalls may be a source of foodborne disease. PMID- 17333745 TI - Determination of oral microflora in irradiated ocular deformed children. AB - Children with a retinoblastoma usually have enucleation of eye contents and undergo radiation therapy. In this group of children a slight deformation in facial growth is exhibited on the operated side. The radiation affects the oral microflora. This study was conducted to investigate the oral microflora in this group of patients compared to normal children. Nineteen children, ages 4-15 years, were tested for oral microflora by culture. A control group was comprised of 20 normal healthy children from a primary school in Bangkok, Thailand. Paraffin-stimulated whole saliva was collected and cultured for the presence of mutans streptococci, lactobacilli and Candida species. The isolation frequencies and abundances of lactobacilli and Candida species in saliva samples of irradiated children were significantly greater than healthy children. The mutans streptococci counts were significantly different from healthy controls. Radiation therapy may have had some influence on the oral ecology of these patients, so had a higher risk of caries and candidiasis than the healthy controls. Therefore, comprehensive preventive measures should be taken in these children. PMID- 17333746 TI - Factors related to volunteer comprehension of informed consent for a clinical trial. AB - The informed consent process has become a universal requirement for research involving human subjects. Its goal is to inform volunteers regarding research in order to make decision to participate or not. This study aimed to measure volunteers' comprehension levels concerning the clinical trial and to find out factors associated with that comprehension levels. Eighty-one volunteers who enrolled in a malaria clinical trial were recruited into the study. A semi structured questionnaire was used to collect the information. Non-participant observation was used to observe the process of informed consent. Volunteers were interviewed three days after being recruited into the trial. The results show the volunteers' comprehension was low. Only 44% of volunteers had an acceptable level of comprehension. It also revealed that 20 volunteers were not aware of being volunteers. Most volunteers knew about the benefits of participating in the trial and realized that they had the right to withdraw from the study, but not many knew about the risks of the trial. The results indicated the method of informing about the trial affected the volunteers' comprehension level. No relationship was found between comprehension level and volunteers' socio-demographic characteristics and their attitude toward the consent process. The findings from this study demonstrate volunteers who participated in the clinical trial were not truly informed. Further studies regarding enhancing volunteers' understanding of the trial are needed. PMID- 17333747 TI - Prevalence and risk factors of hypercholesterolemia among Thai men and women receiving health examinations. AB - The purpose of our study was to evaluate risk factors for hypercholesterolemia and correlates of serum lipid concentrations in Thai men and women. A cross sectional study was conducted in 1392 patients (380 men and 1012 women) who received health examinations during July 1999 - February 2000 at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Serum total cholesterol (TC), triglyceride (TG) and high density lipoprotein- cholesterol (HDL-C) concentrations were determined using standard procedures. Logistic and linear regression procedures were used to assess the association of several covariates with risk for hypercholesterolemia. The results reveal that the prevalences of hypercholesterolemia (TC > or =200 mg/dl) among men and women were 66.8% and 66.0%, respectively. Among men, hypercholesterolemia was associated with older adults (OR = 3.26), and previous alcohol consumption (OR = 2.05). Risk factors for women included advanced age (OR = 3.19), and a family history of dyslipidemia (OR = 1.59). Serum TC and TG were positively associated with age and previous alcohol consumption among men. Among women, TC and TG were strongly associated with age, body mass index (BMI) and family history of dyslipidemia. In men and women, HDL-C was inversely associated with BMI. More emphasis should be placed on understanding the epidemiology of hypercholesterolemia and other dyslipidemias in Thai men and women. More information regarding risk factors will aid in the development of effective health promotion and disease prevention efforts. PMID- 17333748 TI - Red cell immunization in multiply transfused Malay thalassemic patients. AB - The development of red blood cell (RBC) isoimmunization with alloantibodies and autoantibodies complicate transfusion therapy in multiply transfused thalassemia patients. Thus, the frequency, causes and prevention of these phenomena were studied among these patients. Clinical and serological data from 58 Malay multiply transfused thalassemic patients who sought treatment at Hospital University Sains Malaysia were collected and analyzed prospectively. Blood samples were subjected to standard blood bank procedures to screen for antibody and subsequent antibodies identification. All patients in our hospital received blood matched for only ABO and Rh (D) antigens. There were 46 (79.3%) patients with Hb E/beta thalassemia, 8 (13.8%) with beta thalassemia major, 3 (5.2%) with Hb H Constant Spring and 1 (1.7%) with Hb H disease. Overall, 8.6% of the patients had alloantibodies and 1.7% had autoantibodies. The alloantibodies identified were anti-E, anti-c, anti-K, anti-Jka, anti-N and anti-S. In conclusion, the transfusion of matched blood is essential for chronically multiply transfused patients in order to avoid alloimmunization. Considering the high frequency of anti E at our hospital, it is advisable to genotype patients and match the red cells for E antigens in multiply transfused thalassemia patients. PMID- 17333749 TI - Prenatal exclusion of Pompe disease by electron microscopy. AB - Pompe disease is a lysosomal storage disorder caused by alpha-glucosidase deficiency. The disease is characterized by accumulation of glycogen in the lysosomes. The accumulation has unique ultrastructural features which enable a prenatal diagnosis by electron microscopy. We describe prenatal electron microscopic testing in a fetus of a mother whose previous child died of Pompe disease. The disease in the affected child was diagnosed by a decrease in alpha glucosidase activity of his skin fibroblasts. Electron microscopy of the chorionic villus sample and amniocytes revealed normal findings, thus predicting an unaffected fetus. The study was confirmed by the birth of a normal neonate who was still healthy at the age of 12 months. Electron microscopy is useful in the first and second trimesters to exclude Pompe disease prenatally. This test can be use prenatally and provides families with reassurance. PMID- 17333751 TI - Clinical severity and financial burden among road traffic injury patients in Kunming, China. AB - This study aimed to describe the severity of injury (RTI), length of stay, costs, financial burden, and sources of payment for RTI patients in the Kunming area, Yunnan Province, China. Information was collected from interviewing 420 patients admitted with RTI during January to May 2005 and from medical records reviewed of all the patients admitted from January to 30 May 2005. The costs and financial burden of road casualties on the medical sector resources were found to be large (median = RMB 94,496) compared to the average per capita monthly income of the Yunnan population (RMB 798). Most patients had injuries of moderate severity. Pedestrians and passengers had the highest Injury Severity Score (ISS). The mean payments out-of-pocket, from the government and by compensation were RMB 5320, 10,190 and 11,190, respectively. In addition to prevention of RTI, a suitable insurance system is needed in the country. PMID- 17333750 TI - Prevalence of asthma, rhinitis, and eczema among children in Vientiane city, Lao PDR. AB - An International Study of Asthma and Allergy in Childhood (ISAAC) revealed a wide range of prevalences of childhood asthma in the world. Lao PDR had no such epidemiological data yet. This study aimed to investigate the epidemiology of asthma, rhinitis, and eczema in children in the country. A cross-sectional study was conducted in Vientiane City, the capital of Lao PDR, in 1997 using the ISAAC questionnaire. From three primary schools and one high school, 395 children, age 6-7 years, and 468 children, age 13-14 years, were chosen. The prevalence of asthma for children aged 13-14 years in Lao PDR was 25.6%, which ranks the highest in international asthma prevalence. The prevalence in allergic rhinoconjunctivitis of children was 24.4% and atopic eczema was 7.1%. Contrary to generally accepted risk factors, there were no associations revealed between asthma prevalence and smoking of family members (especially mothers), intake of fish/meat, and male gender. PMID- 17333752 TI - The relationship between health behavior and pain scale in patients with low back pain in Thailand. AB - The purpose of the study was to evaluate the relationship between health behavior and pain scale in patients with low back pain. One hundred eighty patients with low back pain attending the Orthopedic Unit at Sapasithiprasong Hospital in Thailand participated in the study. The participants completed a questionnaire related to demographic data and preventive health behavior, illness health behavior and sick role health behavior. Statistical analysis was used to calculate means, standard deviations and percentages, multiple regression evaluated the relationship between demographic data and pain scale, and Pearson's correlation assessed the relationship between the three health behaviors and pain scale. Generally, the results showed most participants had a lower quality of health behavior. The most common causes of low back pain were lifting heavy loads, incorrect positioning and everyday activity (43.9, 17.8 and 10.6%, respectively). The level of participant's income was found to be statistically relevant to pain scale (p < 0.05). There was also a statistically significant association between the three health behaviors and pain scale (p = 0.0001, 0.005, 0.0001, respectively). The findings of this study illustrate the crucial role that Thai health care professionals play in changing the health behavior of patients with low back pain in order to improve the patient's quality of life. PMID- 17333753 TI - A study of melatonin levels and stress in female shift workers. AB - The aim of this study was to determine the relationship between saliva melatonin and stress levels in Thai female shift workers. Five older (38.4 +/- 1.82) and five younger (21.4 +/- 0.55) female workers voluntarily participated in this study. All participants worked both morning and night shifts at a glass manufacturing factory. Saliva was collected every three hours at the workplace and at the subjects' houses to examine melatonin profiles. The Mann-Whitney U test and the Wilcoxon signed ranks test were used. There was a significant (p < 0.05) difference between melatonin levels in younger and older subjects when measured during the night shift at 19:00. Differences between melatonin levels during the morning and night shifts in the older group were significant at 07:00 and at 19:00 in younger subjects (p < 0.05). Normal stress and mild stress were found. No significant differences in melatonin levels were found between workers with normal and mild stress levels. The onset time of increasing saliva melatonin was at 19:00, both in women working the morning shift and in those working the night shift. Peak melatonin production occurred at 22:00 for the night shift in both groups. During the morning shifts, the peak times were at 04:00 and 01:00 (in the younger and older groups, respectively), usually between 02:00 and 04:00. These findings show that melatonin levels in female shift workers adapted according to the shift worked, especially in the older group. Health surveillance programs should therefore be established to prevent further negative health effects for female shift workers. PMID- 17333754 TI - Prevalence and socio-demographic factors associated with tobacco smoking among adult males in rural Sindh, Pakistan. AB - This cross-sectional study was undertaken to determine the prevalence of tobacco smoking and to obtain information on socio-demographic factors associated with tobacco smoking among adult males in a rural district of Sindh Province, Pakistan. We used a one-stage cluster sampling frame to identify 411 adult males from the study site. We found a high prevalence, 55% of current smokers among this rural population. The median age of initiation of smoking was 20 years. Awareness of the adverse effects of smoking on lung and heart diseases was 86% and 77%, respectively. Smoking prevalence increased with age and income, and was highest among subjects aged 44 years and above (76%) and with incomes of more than PKR 4000 (72%). The high prevalence of smoking suggests that there is an urgent need for developing intervention plans to address this major public health problem in this region. PMID- 17333755 TI - Early detection of malaria in an endemic area: model development. AB - A malaria epidemic warning system was established in Thailand in 1984 using graphs displaying the median or mean incidence of malaria over the previous five years compiled from malaria surveillance data throughout the country. This reporting mechanism is not timely enough to detect the occurrence of a malaria epidemic which usually occurs at the district level over a short period of time. An alternative method for early detection of a malaria epidemic employing the Poisson model has been proposed. The development of this early malaria epidemic detection model involved 3 steps: model specification, model validation and model testing. The model was based on data collected at the Vector Borne Disease Control Unit (VBDU) Level. The results of model testing reveal the model can detect increasing numbers of cases earlier, one to two weeks prior to reaching their highest peak of transmission. The system was tested using data from Kanchanaburi Province during 2000 to 2001. Results from model testing show the model may be used for monitoring the weekly malaria situation at the district level. The Poisson model was able to detect malaria early in a highly endemic province with a satisfactory level of prediction. As the application is essential for the malaria officers in monitoring of malaria epidemics, this early detection system was introduced into malaria epidemiological work. The model may be helpful in the decision making process, planning and budget allocation for the Malaria Control Program. The software for early malaria detection is currently implemented in several endemic areas throughout Thailand. PMID- 17333756 TI - In vitro antiplasmodial activity and cytotoxicity of newly synthesized N-alkyl and N-benzyl-1,10-phenanthroline derivatives. AB - A previous study showed that the 1,10-phenanthroline skeleton was active in vitro against chloroquine-resistant and sensitive strains of Plasmodium falciparum. Based on this skeleton, 8 derivatives of N-alkyl and N-benzyl-1,10 phenanthrolines have been synthesized. This study was conducted to evaluate the in vitro antiplasmodial activity and cytotoxicity of these compounds. The in vitro antiplasmodial activity was tested on two strains of P. falciparum, FCR-3 chloroquine-resistant and D10 chloroquine-sensitive strains, while their cytotoxicity was tested on the Vero cell line. The parasite and cell growth were estimated by hypoxantine-[2,8-3H] uptake after 24- and 72-hour incubation with each compound tested. The control parasite or cell free from any compounds was referred to as having 100% growth. For this radioactive method, the IC50 value showing concentration inhibiting 50% of the parasite growth was determined by probit analysis. The results showed that the highest antiplasmodial activity was observed with (1)-N-benzyl-1,10-phenanthrolinium iodide with the IC50 0.18-0.45 microM, and the IC50 of the compound on Vero cells ranged from 2,582.30 to 7,057.71 microM. The cytotoxic/ antiplasmodial ratio indicates that this compound has high selectivity (10,993 +/- 330.79-38,965 +/- 6,888.27). PMID- 17333757 TI - Seroprevalence of Trichinella in slaughter pigs in Kathmandu Valley, Nepal. AB - The aim of the present study was to determine the Trichinella seroprevalence in slaughter pigs in Kathmandu Valley, Nepal. Serum samples were obtained from 400 pigs at 4 major slaughterhouses and tested for Trichinella antibodies by ELISA using larval excretory-secretory (E/S) antigen. Four were positive and one was equivocal, giving a Trichinella seroprevalence of 1% (95% CI: 0.27 - 2.54). On titration, all positive and equivocal samples had titers greater than 1:80. Upon re-examination the equivocal sample failed to give a positive ELISA result. The pigs were from four major areas of Nepal, Kathmandu Valley, eastern Nepal, Terai and adjoining areas of the valley. Positive results were found from only Kathmandu Valley and adjoining areas. There was no significant difference in the prevalence between areas (p = 0.43). All four positive samples were from indoor managed pigs. The Trichinella seroprevalence determined in this study deserves a direct demonstration of the parasites for proof of the presence of Trichinella in Nepal and to discover the species and infection sources. PMID- 17333758 TI - Epidemiology of food-borne trematodes and other parasite infections in a fishing community on the Nam Ngum reservoir, Lao PDR. AB - Food-borne trematodes (FBT) are important causes of parasitic infections in many Asian countries. Parasitological surveys in Xai Udom, a small fishing community on the Nam Ngum reservoir, Lao People's Democratic Republic, revealed an overall parasitic infection rate in May 1999 of 68.8% (n = 173) and in December 1999 of 65.9% (n = 261). The liver fluke, Opisthorchis viverrini accounted for most of the infections (prevalences of 53.8% and 42.1%, during the first and second surveys, respectively). The prevalence and intensity showed increasing trends with age. Minute intestinal flukes were also present but with relatively low infection rates (3.8-10.9%). The second common group of parasites comprised soil transmitted nematodes, Trichuris trichiura, Ascaris lumbricoides, hookworm and Strongyloides stercoralis, with prevalences of 22.4 and 17.6%, 20.8 and 8.0%, 16.8 and 13.4%, and 4.0 and 15.3% (first and second surveys, respectively). Most people had no or only light infections, with a few people having heavy infections. Coexisting intestinal protozoa were Giardia lamblia (5.2 and 4.9%) and Entamoeba coli (6.9 and 6.5%). Concurrent tapeworm infections were Taenia (1.7 and 1.1%) and Hymenolepis nana (0.7 and 0.6%) (first and second surveys, respectively). Despite the availability of effective anthelmintic drugs, the results of our study reaf-firm that FBT are still a major health threat in this fishing area of Lao PDR, similar to a decade ago. PMID- 17333759 TI - Evaluation of coverage of deworming interventions in Vietnam. AB - In 2004-2005, the school deworming program in Vietnam targeted 2,400,000 school children in 25 provinces. A questionnaire survey of a random sample of schools throughout the country was organized to validate the teacher feedback, assess the real coverage of the program and estimate the occurrence of side-effects. A total of 91 schools in four different provinces were visited few days after drug distribution. A total of 2,323 children and 80 teachers were questioned. The total cost of the monitoring has been estimated at US dollar 7,000 (less than 10% of the deworming program). The survey demonstrated a coverage of 95% for school children and of 86.3% for teachers (on average a coverage 2% lower than the one reported by the teachers through forms on the day of drug administration). Approximately 0.4% of those interviewed reported side-effects after deworming, while the occurrence of side effects through routine reports was 0.15%. In both cases, the side effects were described as mild forms of nausea, abdominal pain, or headaches that did no required pharmacological treatment. The survey confirmed the positive results of routine reporting; we consider the survey a cost effective activity to maintain the control activities under monitoring. PMID- 17333760 TI - Appreciation of school deworming program by parents in Ha Giang Province (Vietnam). AB - School-based deworming programs are one of the most cost-effective public health strategies to reach children with anthelminthics and health education. However, despite their low cost and high health impact, they are not implemented on a large scale. The present survey investigated a school-based deworming program in Ha Giang Province, Vietnam, to assess the community perception and support towards these programs. Information from 81 households, 88 primary school students, 25 teachers and 9 people in charge of commune health stations was collected by structured questionnaires. The survey displayed complete satisfaction and a high level of support within all 4 questioned groups. In addition 96.1% of all parents noticed an improvement in their children's health. The great appreciation of the deworming program by the community is an additional argument to convince decision makers to implement and scale up these programs. Even teachers that did not receive any specific training were able to distribute the drug successfully following the page of written instructions accompanying the drug. PMID- 17333761 TI - Ganoderma lucidum: a cause of pseudoparasitosis. AB - We report a pseudoparasitosis case due to Ganoderma lucidum, (lingzhi or reishi mushroom); we believe this to be a first reported case in Thailand. A 49-year-old male patient with non-Hodgkins lymphoma presented with chronic watery diarrhea. He had a history of consumption of powdered lingzhi extract as a dietary supplement and herbal medicine. Stool examination demonstrated many spores of G. lucidum, which must be differentiated from intestinal helminth ova and coccidia. After discontinuation of mushroom spores ingestion, the diarrheal symptoms improved and fecal examination subsequently showed no Ganoderma spores. Many artifacts in the stool may be confused with parasites. Differentiation of parasites from artifacts depends on characterization of the size, shape, structure, and reactivity with common stains. PMID- 17333762 TI - Climatic factors associated with epidemic dengue in Palembang, Indonesia: implications of short-term meteorological events on virus transmission. AB - An extensive outbreak of dengue fever and dengue hemorhagic fever occurred in the city of Palembang, South Sumatra, Indonesia from late 1997 through March/April 1998. All surveyed administrative areas (kelurahan) in Palembang were found to be 'permissive' for dengue virus transmission; and all areas that had Aedes (subgenus Stegomyia) larval mosquitoes in abundance experienced increased cases of DHF during the epidemic. The Aedes House Index (HI) for combined Aedes aegypti and Aedes albopictus was recorded every 3 months before, during, and after the epidemic. Ten surveyed sentinel sites (October-December 1997) immediately preceding the epidemic peak had a combined HI of 25% (range 10-50.8%). Entomological surveys during the peak epidemic period (January-April) showed a combined HI of 23.7% (range: 7.6-43.8%). Kelurahans with the highest numbers of reported dengue cases had an HI exceeding 25%; however, there was no discernable relationship between elevated HI and increased risk of DHF incidence. Despite the unusual climatic conditions during late 1997 created throughout the region by the El Nino Southern Oscillation (ENSO), the house indices during both wet and dry months remained above 23% for the 4 quarterly (3-month) periods surveyed in the second half of 1997 and first half of 1998. Rainfall returned to near normal monthly levels shortly before the reported increase in human cases. However, mean ambient air temperatures continued above normal (+0.6 to 1.2 degrees C) and were sustained over the months leading up to and during the epidemic. Evidence suggests that an ENSO-driven increase in ambient temperature had a marked influence on increased virus transmission by the vector population. We explore the apparent associations of entomological and climatic effects that precipitated the epidemic before the influx of reported human cases. PMID- 17333763 TI - Rapid detection of dengue viral RNA in mosquitoes by nucleic acid-sequence based amplification (NASBA). AB - RNA amplification by nucleic acid sequence-based amplification (NASBA) was used to detect serotype specific dengue viruses in artificially-infected female Aedes mosquitoes, in comparison with RT-PCR technique. NASBA could detect dengue virus serotype 2 and 4 below 0.1 PFU, which was more sensitive than RT-PCR, but this technique was as sensitive as RT-PCR when detecting dengue virus serotype 1 and 3. Dengue viruses could be detected at the thorax of mosquitoes at 0, 7, and 14 days after inoculation with dengue virus serotype 2. This method should be useful for virological surveillance of dengue infected Aedes mosquitoes, as an early warning system to predict outbreaks of dengue viruses. PMID- 17333764 TI - Incidence and clinical manifestations of rotavirus infection among children with acute diarrhea admitted at Buri Ram Hospital, Thailand. AB - To study the incidence and clinical manifestations of rotavirus among children at Buri Ram Hospital, admitted with the diagnosis of acute diarrhea between November 2005 and February 2006. In the course of a cross sectional descriptive study, 103 stool samples obtained from inpatients below the age of 5 years were examined for rotavirus by RT- PCR. Data on clinical manifestations, complications, administration of antibiotics, length of admission and hospital cost were obtained by means of questionnaires distributed among physicians. The statistics used were presented as percentage, mean and 95% confidence interval, while chi square and unpaired t-test were used to establish significant differences at p < 0.05. Rotavirus was detected in 45 of 103 stool samples (43.68%, 95%CI = 33.93, 53.81). No significant differences were found between clinical manifestations of children with rotavirus infection and non-rotavirus infection as both groups displayed acute watery diarrhea (p = 0.33), fever (p = 0.80), nausea or vomiting (p = 0.08), predominant lymphocytes (p = 0.54), absence of red blood cells (p = 0.63) or white blood cells (p = 0.57) in the stool examination, moderate or severe dehydration (p = 0.06), lactose intolerance (p = 0.41), hypokalemia (p = 0.55), metabolic acidosis (0.18) Administration of antibiotics was significantly reduced for treatment of rotavirus acute diarrhea (31.1% vs 63.8%, p = 0.001). Hospital cost and length of admission were significantly reduced in rotavirus acute diarrhea (1,845.04 baht vs 2,297.00 baht, p < 0.01) (2.09 days vs 2.81 days, p < 0.001). Compared to previous studies, no differences were found in the percentage of rotavirus acute diarrhea. Rotavirus infection is a major cause for hospitalization of children below the age of 5 years with acute diarrhea. Clinical characteristics of rotavirus acute diarrhea were not significantly different from those due to other etiologies. Diagnosis of rotavirus infection should be based on various clinical manifestations and specific laboratory methods. Further studies on the cost benefit of rotavirus vaccine in Thailand ought to be performed before implementing a universal vaccination program. PMID- 17333765 TI - Respiratory syncytial virus is not an important community acquired pathogen in adult hematological malignancy patients. AB - Respiratory syncytial virus (RSV) has been reported as a leading cause of upper and lower viral respiratory tract infection in high-risk adult populations. We prospectively studied 48 patients with hematological malignancies over a period of 2 years. Throat and nasal washings were subjected to immunofluorescence and cell culture for virus isolation. Of these 48 patients, 31 had acute leukemia, 6 had chronic leukemia, 10 had lymphoma and one had multiple myeloma. The median age of the patients was 20 years with a male to female ratio of 4:1. No RSV was detected in any of the samples. RSV was not found as a major cause of community acquired upper respiratory tract infections in adults with hematological malignancies in India. PMID- 17333766 TI - Characterization of ITS2 rDNA of Anopheles philippinensis and Anopheles nivipes (Diptera: Culicidae) from north-east India. AB - Anopheles (Cellia) philippinensis Ludlow and Anopheles (Cellia) nivipes (Theobald) are two closely related, morphologically very similar, mosquito species in the Annularis group, which play a supportive role in malaria transmission in north-east India. We amplified and performed sequence analysis for the internal transcribed spacer 2 (ITS2) locus of ribosomal DNA (rDNA) gene of morphologically confirmed specimens of these two species from the states of Assam and Nagaland. An. philippinensis and An. nivipes shared 85.2% sequence similarity and no intra-species variation was found in the nucleotide sequences of the two species. Overall, sequence data of the ITS2 marker revealed that both these species from north-east India differed by as much as have been reported from specimens of eastern Thailand. PMID- 17333767 TI - Comparative field evaluation of residual-sprayed deltamethrin WG and deltamethrin WP for the control of malaria in Pahang, Malaysia. AB - The bioefficacy of indoor residual-sprayed deltamethrin wettable granule (WG) formulation at 25 mg a.i./m2 and 20 mg a.i./m2 for the control of malaria was compared with the current dose of 20 mg/m2 deltamethrin wettable powder (WP) in aboriginal settlements in Kuala Lipis, Pahang, Malaysia. The malaria vector has been previously identified as Anopheles maculatus. The assessment period for the 20 mg/m2 dosage was six months, but for the 25 mg/m2 dosage, the period was 9 months. Collections of mosquitoes using the bare-leg techniques were carried out indoors and outdoors from 7:00 PM to 7:00 AM. All mosquitoes were dissected for sporozoites and parity. Larval collections were carried out at various locations to assess the extent and distribution of breeding of vectors. A high incidence of human feeds was detected during May 2005 and a low incidence during January 2005 for all the study areas. Our study showed that deltamethrin WG at 25 mg/m2 suppressed An. maculatus biting activity. More An. maculatus were caught in outdoor landing catches than indoor landing catches for all the study areas. The results indicate that 25 mg/m2 WG is good for controlling malaria for up to 9 months. Where residual spraying is envisaged, the usual two spraying cycles per year with 20 mg/m2 deltamethrin may be replaced with 25 mg/m2 deltamethrin WG every 9 months. PMID- 17333768 TI - SCCmec typing and detection of VISA-related genes in methicillin-resistant Staphylococcus aureus clinical strains from Kobe University Hospital, Japan. AB - A total of 50 clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) were collected from Kobe University Hospital in 2003. Molecular typing of SCCmec was performed by multiplex polymerase chain reaction (PCR) and the presence of six genes (vraR, vraG, vraA, vraF, fruA, and fruB) associated with vancomycin (VCM) resistance was examined by simple PCR analysis. Out of 50 MRSA strains isolated 47 strains contained Type II SCCmec and the remaining contained Type IV SCCmec. Thirty seven strains contained pUB110 plasmid. VraA was present in 69% of the strains, vraF in 10%, vraG in 53%, and vraR in 16%. Noteworthy, strains without pUB110 contained vraR in relatively higher frequency (31%) compared with strains with pUB110 (11%). PMID- 17333769 TI - Antimicrobial activity of Cratoxylum formosum on Streptococcus mutans. AB - The gum of Cratoxylum formosum, commonly known as mempat, is a natural agent that has been used extensively for caries prevention by hill tribe people residing in Thailand. The objective of this study was to investigate the antimicrobial activity of Cratoxylum formosum gum on Streptococcus mutans (S. mutans) in vitro. The gum extracted from stem bark of Cratoxylum formosum was investigated for antimicrobial activity against different strains of S. mutans, including S. mutans KPSK2 and 2 clinical isolates. Inhibition of growth was primarily tested by agar diffusion method. A two-fold broth dilution method was then used to determine the minimum inhibitory concentration (MIC) of the extract. The extract of Cratoxylum formosum was effective against S. mutans with the inhibition zones ranging from 9.5 to 11.5 mm and MIC values between 48 microg/ml and 97 microg/ml. The gum of Cratoxylum formosum has high antimicrobial activity against S. mutans and may become a promising herbal varnish against caries. PMID- 17333770 TI - Ecology of Clostridium botulinum causing food-borne botulism in Thailand. AB - The objective of this study was to determine ecology of Clostridium botulinum from previous reported outbreaks. Geographical parameters and their corresponding settings were collected and analyzed. The averages (mean +/- SD) for % soil moisture, % humus and pH were 0.6 +/- 0.1% (range 0.5-0.7), 3.0 +/- 0.2% (range 3 3.2) and 5.2 +/- 0.1 (range 5.1-5.4), respectively. All outbreak settings shared the same sandy loam soil type. It can imply that provinces with this type of ecology may have sites harboring C. botulinum. PMID- 17333771 TI - Comparison of media and antibiotic supplements for isolation of Helicobacter pylori from gastric biopsies. AB - Our objective was to improve the media and the antibiotic supplements in order to increase the detection rate of Helicobacter pylori from gastric biopsy specimens. For the primary isolation of H. pylori taken from gastric biopsies, we compared the efficacy of two media: Columbia blood agar (CBA, Difco); brain heart infusion agar (BHIA, Difco); and two antibiotic supplement sets--a commercial antibiotic supplement (SR147, Oxoid) and an in-house antibiotic supplement (IHS). Gastric biopsies obtained from 210 patients were diagnosed by culture, rapid urease test (RUT) and histology. The true positive criteria were defined as a culture or both urease and histology tests being positive. The H. pylori infection rate was 44.3% (93/ 210). To compare the two media, a total of 106 gastric biopsies were plated on CBA or BHIA with 7% human blood, containing the antibiotic supplement SR147 and incubated under microaerophilic conditions. Of the 106 samples, 48 (45.3%) case of H. pylori infection, compared to the true positive criteria. The isolation rate using a combination of the two media was 83% (40/48). Of the 40 samples, 36 (90%) and 35 (87.5%) were positive on CBA and BHIA, respectively. To compare the two antibiotic supplement sets, a total of 104 gastric biopsies were plated on CBA, containing the commercial antibiotic supplement SR147 (5 mg/l trimethoprim, 10 mg/l vancomycin, 5 mg/l amphotericin B and 5 mg/l cefsulodin) or containing IHS (5 mg/l trimethoprim, 10 mg/l vancomycin, 2 mg/l amphotericin B and 2,500 U/l polymyxin B). Of the 104 samples, 45 (43.2%) case of H. pylori infection were found compared to the true positive criteria. The isolation rate using a combination of the two selective supplement sets was 82% (37/45). Of the 37 samples, 35 (95%) and 34 (92%) were positive with SR147 and IHS, respectively. Our study indicates that the combination of the two media and two antibiotic supplements is useful for maximum recovery of H. pylori isolated from gastric biopsies. CBA, and the commercial antibiotic supplement SR147 provided higher detection rates for H. pylori than BHIA, and IHS but the differences were not statistically significant. PMID- 17333772 TI - Typhoid fever: narrowing therapeutic options in India. AB - Typhoid fever remains an important public health problem in India. One thousand four hundred fifty-eight blood cultures were screened, 178 grew out Salmonella enterica serovar Typhi. On agar dilution minimum inhibitory concentration (MIC) testing, 0.6% of the isolates were resistant to ciprofloxacin, 2% to cefotaxime and 1% to cefepime. Nalidixic acid resistance was observed in 51% isolates, of which 98.9% had decreased susceptibility (MIC > or = 0.125-4 microg/ml) to ciprofloxacin. One strain of nalidixic acid sensitive S. Typhi (NASST) also had a decreased MIC (0.125 microg/ml) to ciprofloxacin. Resistance to third and fourth generation cephalosporins is emerging in India and will gain significance in the coming decade. The molecular basis of resistance to cephalosporinsand ciprofloxacin resistance in NASST strains need to be further evaluated for S. Typhi. PMID- 17333773 TI - Neonatal sepsis caused by Salmonella enterica serovar Weltevreden. AB - Salmonella enterica serovar Weltevreden is an uncommon cause of gastroenteritis occurring worldwide. For the first time, we report 2 cases of neonatal sepsis caused by S. Weltevreden from Hubli, India. In the first case, the neonate had features of septicemia and S. Weltevreden was isolated from a blood culture. The other neonate had omplalitis and clinical features of septicemia. S. enterica serovar Weltevreden was isolated from the umbilical swab culture of this neonate. Even though extensive investigations were conducted, the source of infection could not be identified. Both neonates recovered completely after appropriate antibiotic and supportive therapy. PMID- 17333774 TI - A fatal case of Chromobacterium violaceum septicemia in Hong Kong. AB - Chromobacterium violaceum causes a rare infection in human, usually in tropical or subtropical areas. We report a fatal case of C. violaceum infection affecting a 40-year-old previously healthy man in Hong Kong. He presented with a wound infection and lymphadenitis. Despite multiple antibiotic treatment, including ciprofloxacin, he succumbed shortly after admission to the hospital. We report the epidemiological investigation findings and discuss the possible sources of infection. Physicians should be alert to this rare but fatal infection. Injury prevention and proper wound care should be emphasized to the public. PMID- 17333775 TI - Invasive infection due to Moraxella lacunata, an unusual pathogen. AB - Moraxella lacunata, a commensal bacterium, is associated with serious invasive disease. We describe a patient with diabetic nephropathy who developed septicemia with metastatic abscesses in the liver and spleen due to Moraxella lacunata. The patient also had multiple ring enhancing lesions in both the cerebral hemispheres, possibly due to the same organism. PMID- 17333776 TI - Evaluation of a microcolony detection method and phage assay for rapid detection of Mycobacterium tuberculosis in sputum samples. AB - Early and rapid diagnosis of tuberculosis is necessary for both treatment and control of the disease. This study evaluated two microcolony observation techniques based on liquid and solid media and a mycobacteriophage assay, to evaluate their effectiveness in the diagnosis of pulmonary TB compared with a standard culture (BACTEC 460 and LJ medium). Middlebrook7H9 (M7H9) broth based on microcolony determination detected 57/61 positives cultures (n = 200) with a sensitivity of 93.4% and a specificity of 87.1%. M7H11 agar detected 57/62 positive cultures (n = 198) with a sensitivity of 91.9% and a specificity of 89.7%. The mycobacteriophage assay detected 98/143 (68.5%) of positive samples. The time to positivity was 48 hours in the mycobacteriophage assay versus 7 days in both the M7H9 broth and M7H11 agar. The costs in comparison with the culture (BACTEC 460 and LJ) were 33% and 48% for the microcolony and mycobacteriophage methods, respectively. Microcolony methods were rapid and cost effective compared to standard cultures. The mycobacteriophage assay, despite its lower sensitivity, has a short turn around time, and may be recommended as a screening test in countries with a low prevalence of tuberculosis. PMID- 17333777 TI - Tubercular splenic abscess in an immunocompetent patient--a rare entity. AB - Tubercular splenic abscess is an uncommon entity. It has been reported in association with immunodeficiency states. Tubercular splenic abscess in an immunocompetent patient is extremely rare. A 24 year old female who had already received a complete course of anti-tubercular therapy (ATT) for pulmonary tuberculosis was diagnosed as having tubercular splenic abscess. She was successfully managed by performing splenectomy. Operative findings and histopathological examinations confirmed the diagnosis. PMID- 17333778 TI - Referral of epileptic patients in North East Coast of West Malaysia an area with poor MRI coverage: an analysis. AB - Advances in neuroimaging techniques, particularly Magnetic Resonance Imaging (MRI), have proved invaluable in detecting structural brain lesions in patients with epilepsy in developed countries. In Malaysia, a few electroencephalography facilities available in rural district hospitals run by trained physician assistants have Internet connections to a government neurological center in Kuala Lumpur. These facilities are more commonly available than MRI machines, which require radiological expertise and helium replacement, which may problematic in Southeast Asian countries where radiologists are found in mainly big cities or towns. We conducted a cross-sectional study over a two year period begining January 2001 on rural patients, correlating EEG reports and MRI images with a clinical diagnosis of epilepsy to set guidelines for which rural patients need to be referred to a hospital with MRI facilities. The patients referred by different hospitals without neurological services were classified as having generalized, partial or unclassified seizures based on the International Classification of Epileptic Seizures proposed by the International League Against Epilepsy (ILAE). The clinical parameters studied were seizure type, seizure frequency, status epilepticus and duration of seizure. EEG reports were reviewed for localized and generalized abnormalities and epileptiform changes. Statistical analysis was performed using logistic regression and area under the curve. The association between clinical and radiological abnormalities was evaluated for sensitivity and specificity. Twenty-six males and 18 females were evaluated. The mean age was 20.7 +/- 13.3 years. Nineteen (43.2%) had generalized seizures, 22 (50.0%) had partial seizures and 3 (6.8%) presented with unclassified seizures. The EEG was abnormal in 30 patients (20 with generalized abnormalities and 10 localized abnormalities). The MRI was abnormal in 17 patients (38.6%); the abnormalities observed were cerebral atrophy (5), hippocampal sclerosis (4), infarct/gliosis (3), cortical dysgenesis (2) and tumors (2). One patient had an arachnoid cyst in the right occipital region. Of the 17 patients with an abnormal MRI, 14 had an abnormal EEG, this difference was not statistically significant. There was no significant associaton between epileptographic changes and MRI findings (p = 0.078). EEG findings were associated with MRI findings (p = 0.004). The association between an abnormal EEG and an abnormal MRI had a specificity of 82.4%, while epileptogenic changes had a specificity of 64.7% in relation to abnormal MRI findings. This meants that those patients in rural hospitals with abnormal EEGs should be referred to a neurology center for further workup and an MRI to detect causes with an epileptic focus. PMID- 17333779 TI - Clinical outcomes of patients with cardiogenic cerebral emboli in Srinagarind Hospital. AB - We retrospectively studied the functional outcomes and recurrence rates of patients 15 years and older in whom cardiogenic cerebral embolism was diagnosed at Srinagarind Hospital, Khon Kaen, Thailand, during the period of 1993-2002. Ninety patients were included in this study. Ages ranged from 16-80 years (mean 48.3 years). The majority of cardiac abnormalities were rheumatic heart diseases (with or without atrial fibrillation) and nonvulvular atrial fibrillation. At 3 months and 1 year after stroke, improvement in functional outcome (measured by RDS, motor strength, and GCS) were 74.4% and 55.6%, mortality rates of 13.3% and 16.7%; and recurrence rates of 8.9% and 16.7%, respectively. A GCS < 9 or motor power < or = 1 or RDS > or = 4 upon presentation were poor prognostic factors. PMID- 17333780 TI - Risk factors for anemia in Vietnam. AB - Anemia is a significant public health problem in Vietnam, but representative national data and comprehensive risk factors analysis are lacking. The objectives of this study were to: 1) determine the distribution and severity of anemia in Vietnam, and 2) to assess potential risk factors for anemia. Nine thousand five hundred fifty households in 53 provinces were covered using a stratified two stage cluster survey carried out in 1995. Selected household members were interviewed; intestinal helminthes were tested in non-pregnant women by Kato-Katz technique; hemoglobin concentrations were measured with Hemocue. Data were weighted and analyzed by survey procedures using SAS 9.0. Overall, 60% of children under 2 years old, 53% of pregnant women, 40% of non-pregnant women and 15.6% of men were anemic. Hookworm infection was the strongest factor associated with anemia (OR = 1.7; 2.9 and 4.5 for 11,999, 2,000-3,999 and > or = 4,000 hookworm egg counts, respectively) and accounted for 22% of anemia. Hookworm intensity was significantly associated with hemoglobin level; for each 1,000 egg increase, hemoglobin was reduced by 2.4 g/l. Living in different ecological zones, eating < 1 serving of meat/ week, and farming were significantly associated with anemia in women and children. Other risk factors in women included having > 3 children and having a child < 24 months old. In men, no variables were found significantly associated with anemia. PMID- 17333781 TI - Elevated red cell volume in North Indian students. AB - In a survey for beta-thalassemia carrier status among students in the State of Punjab in India, a surprisingly large number were found to have an elevated red cell volume over 99 fl. The finding was predominantly but not exclusively in females. Similar student surveys from other states showed less macrocytosis. Follow-up tests in a group of affected students were carried out. Volunteers were asked to modify their diet then after six months they were provided with oral vitamin B12. The resulting changes are reported and the implications of the probable vitamin B12 and or folic acid deficiency are considered. PMID- 17333782 TI - Preventing avian influenza in humans: the role of simple public health interventions. AB - An influenza pandemic due to influenza virus A H5N1 subtype is considered highly likely. Strategies for prevention and control of a pandemic include actions that need to be taken by the national authorities and communities. The availability of a vaccine and antiviral drugs in sufficient quantities for billions of people in the developing world is doubtful. Simple cost effective public health interventions can significantly reduce the risk of contracting infection. These interventions include precautions that will prevent people from contracting infection from sick or dying poultry and their products, human cases and a contaminated environment. Specific measures are based on principles of cutting short the transmission of infection in humans and inactivating the virus at its source. The paper describes context specific actions that can be implemented in both rural and urban settings by the communities themselves. PMID- 17333783 TI - Microbial contamination of pig carcasses at a slaughterhouse in Vientiane capital, Lao PDR. AB - A cross-sectional study was conducted to determine microbial contamination of pig carcasses at a slaughterhouse in Vientiane, capital of Lao People Democratic Republic (Lao PDR). Between November 2004 and April 2005, 62 pig carcasses were randomly selected. From each carcass, pooled swabs (from "1" prior to and "2" after evisceration) and 25 g of tissue of mesenteric lymph nodes (MLN) were collected. The swab samples were examined for Aerobic Plate Count (APC) and Enterobacteriaceae Counts (EBC) and cultured for Salmonella. The lymph nodes were cultured for Salmonella only. Swabs1 and 2 had mean APC of 4.70 and 4.85 log10CFU/cm2, respectively. These two means were significantly (p = 0.0001) different. The means of EBC were 2.81 log10CFU/cm2 for Swab 1, and 2.98 log10CFU/cm2 for Swab 2. The difference were also statistical significant (p = 0.0001). The frequency of Salmonella isolation from Swab 1 was 46.8%, for Swab 2 was 66.1%, and from mesenteric lymphnodes was 53.2%. Eight different Salmonella serotypes were identified. The most frequent (29.1%) serotype was S. Rissen, followed by S. Anatum (26.2%), S. Derby (18.4%), and S. Elisabethville (8.7%). The other serotypes identified were S. Amsterdam (7.8%), S. Typhimurium (4.9%), S. Agona (2.9%), and S. Enteritidis (1.9%). Results of this study showed the levels of contamination with aerobic bacteria and Enterobacteriaceae were higher than recommended standards, and the carcasses were contaminated with Salmonella. PMID- 17333784 TI - Pattern of health care utilization and determinants of care-seeking from GPs in two districts of Pakistan. AB - The aims of the study were to describe the pattern of health care utilization and out-of-pocket expenses incurred in seeking health care, and to identify the determinants of care-seeking from private general practitioners (GP) in two districts of Pakistan. During July-September 2001, we conducted a cross-sectional study in two districts in the Sindh Province of Pakistan. We selected 1,150 participants age > or = 3 months through a two-stage cluster sampling technique. Information was collected about contacts with healthcare providers during the past three months, presenting complaints, type of treatment received, and cost of the latest visit. Of 1,150 participants, 967 (84%) had at least one contact with health care providers during past three months. The mean number of contacts was 1.7. Most of the contacts (66.8%) were with private GPs. The average cost per visit was Pak Rs 106 (US dollar 1.7) and Rs 38 (US dollar 0.6) for GPs and public sector providers, respectively. A multiple logistic regression model revealed those living in urban areas, with monthly household income > Rs 2,500 (US dollar 39.7), an education level > 5 years, and who received both injections and oral drugs were more likely to visit private general practitioners. PMID- 17333785 TI - Reliability and construct validity of the Malay version of the Job Content Questionnaire (JCQ) among secondary school teachers in Kota Bharu, Kelantan, Malaysia. AB - This study was conducted to assess the reliability and construct validity of the Malay version of Job Content Questionnaire (JCQ) among secondary school teachers in Kota Bharu, Kelantan. A total of 68 teachers consented to participate in the study and were administered the Malay version of JCQ. Reliability was determined using Cronbach's alpha for internal consistency whilst construct validity was assessed using factor analysis. The results indicated that Cronbach's alpha coefficients revealed decision latitude (0.75), psychological job demand (0.50) and social support (0.84). Factor analysis showed three meaningful common factors that could explain the construct of Karasek's demand-control-social support model. The study suggests the JCQ scales are reliable and valid tools for assessing job stress in school teachers. PMID- 17333787 TI - Adjunct therapy with corticosteroids or paracentesis for treatment of tuberculous pleural effusion. AB - To determine the effect of adjunct therapy, we carried out a prospective cohort study on 190 patients with tuberculous pleural effusion during May 2003-April 2004. Patients were divided into 3 groups. All groups were treated with anti tuberculosis (TB) drugs for 6 months; in group 2 (n = 46) prednisolone, 30 mg/day for 10 days, was added; group 3 (n = 78) were given paracentesis to remove fluid. Fever and constitutional symptoms disappeared faster in group 2 (P > 0.05). After 10 days, there was a significantly greater reduction in the size of pleural effusion in group 2, but after 6 months the difference was not statistically significant. We found corticosteroids and therapeutic paracentesis are not necessary in the management of TB pleural effusion. PMID- 17333788 TI - Knowledge of tuberculosis among medical professionals and university students in Oman. AB - This study in Oman investigated knowledge about tuberculosis among 142 medics (medical students, paramedics) and 133 non-medics (arts and social science students). Knowledge was assessed using a validated questionnaire with 28 statements on general knowledge, risk factors and diagnosis of tuberculosis. As expected, tuberculosis knowledge was significantly higher among medics but there was no significant difference between men and women. Although medics had better knowledge in general, some of the technical statements were answered correctly by higher proportions of non-medics. PMID- 17333789 TI - Clinical characteristics of pulmonary tuberculosis in adult Pakistani patients with co-existing diabetes mellitus. AB - A review was made of the records of all patients with pulmonary tuberculosis and diabetes mellitus admitted over a 5-year period to a teaching hospital in Karachi, Pakistan. Among 42358 patients, the total number with both tuberculosis and diabetes was 173. The prevalence of tuberculosis in diabetic patients was 10 times higher than in non-diabetic patients and prevalence increased with duration of diabetes. The lower lung field was most frequently involved, followed by the upper and middle. Bilateral involvement was seen in half and an associated pleural effusion in one-third of the patients. Cavitating lesions were seen in 32% of men and 15% of women. PMID- 17333790 TI - Seroprevalence of hepatitis B in Nahavand, Islamic Republic of Iran. AB - We determined the seroprevalence of hepatitis B in Nahavand in a sample of 1824 subjects > 5 years in 2002. Face-to-face interviews were conducted and blood samples taken. The association between risk factor and hepatitis B was assessed using logistic regression. The prevalence of HBsAg positive cases was 2.3%, and HBcAb and HBsAb were isolated in 7.8% and 11.6% of the participants respectively; 11.9% were positive for both HBcAb and HBsAb. History of surgery and imprisonment were the major risk factors for infection with odds ratios of 2.14 (95% CI: 1.22 3.05) and 3.57 (95% CI: 1.68-5.4) respectively. PMID- 17333791 TI - [Knowledge about hepatitis B and C viruses and HIV among blood donors in Casablanca]. AB - A survey was conducted in the Casablanca Regional Blood Transfusion Centre from February to May 2002. A questionnaire was given to 1750 blood donors from different groups of society to asses the knowledge of the public about hepatitis B and C and human immunodeficiency viruses. The responses indicated that the mechanism of HIV transmission was well known to the public: 85% gave correct answers. Hepatitis B and hepatitis C viruses were less well understood: 60% and 54% gave correct answers respectively. Our study suggests that the public needs to be better informed about hepatitis B and C virus transmission. PMID- 17333792 TI - Albendazole versus metronidazole in the treatment of patients with giardiasis in the Islamic Republic of Iran. AB - We examined the therapeutic effects of albendazole compared to metronidazole in 120 patients with giardiasis in Hamdan. Patients were randomized to receive albendazole (400 mg, once daily for 5 days) or metronidazole (250 mg, 3 times a day for 5 days). Demographic data of the patients, results of stool examination for Giardia trophozoites before and after treatment, and drug side-effects were recorded. After treatment 6 (10.0%) of the albendazole group had trophozoites compared with 14 (23.3%) of metronidazole group (P < 0.05). Patients in the albendazole group had fewer side-effects while 43.3% of the metronidazole group experienced a metallic taste and 35.0% experienced loss of appetite. Albendazole is an easy, safe and effective treatment for giardiasis. PMID- 17333793 TI - Frequency of Giardia lamblia among children in Dohuk, northern Iraq. AB - Out of 1261 stool specimens collected from children in Dohuk city, northern Iraq, the prevalence of Giardia lamblia infection was 38.5%. The highest rate of infection was in orphan care centres (48.1%) and the lowest in the paediatric hospital (31.3%). The age group 10-12 years had the highest rate (81.2%) and 7-9 years the lowest (22.9%); boys had a higher rate than girls. Some infected samples (70/486) showed double or triple infections and G. lamblia was combined with Hymenolepis nana, Blastocystis hominis, Entamoeba histolytica and Iodamoeba buetschlii. PMID- 17333794 TI - Prevalence of helminth ova in soil samples from public places in Shiraz. AB - To determine the prevalence of helminth eggs in public places and children's playgrounds, 112 soil samples were collected in 26 sites in Shiraz, southern Islamic Republic of Iran, during September 2002-September 2003. Toxocara cati ova were found in 7 (6.3%) samples, 2 had Ascaris lumbricoides ova, 3 had larvae morphologically similar to Strongyloides stercoralis. Coccidia oocysts were also observed in 4 samples. No contamination was observed during the dry season. PMID- 17333795 TI - Rapid assessment of trachoma in 9 governorates and Socotra Island in Yemen. AB - This study described the pattern of trichiasis, active trachoma and trachoma risk factors in 9 governorates of Yemen plus Socotra Island, using a rapid assessment during October and February 2004. A total of 3169 children aged 1-9 years were examined in a central meeting point or at home. Active trachoma was found in a high percentage of children in Al-Jawf, Mareb and Shabwah governorates and the SAFE strategy (Surgery, Antibiotic treatment, Facial cleanliness, Environmental improvement) should be directed toward these governorates. Trichiasis cases were also found in Hadramout and Taiz, suggesting that eyelid surgery should be provided in these governorates. PMID- 17333796 TI - Measles seroepidemiology among adolescents and young adults: response to revaccination. AB - We evaluated the seroprevalence of measles antibody and response to measles reimmunization in 590 previously vaccinated adolescents and young adults; 263 were seronegative. To differentiate between primary and secondary vaccine failure, anti-measles IgM and IgG titres were assessed again 2-4 weeks after revaccination in 144 (105 seronegative, 39 seropositive) individuals: 75 seronegative participants responded to revaccination anamnestically (P < 0.001) and developed immunity, 11 also showed IgM response (probably primary vaccine failure); 38 seropositive participants remained seroprotected without significant increase in antibody titre (P = 0.577). Primary vaccine failure was 4.7%; secondary vaccine failure was 27.1%. After revaccination, 87.3% were seroprotected. PMID- 17333797 TI - Coeliac disease in Sudanese children with clinical features suggestive of the disease. AB - Our prospective hospital-based study examined frequency, clinical presentation and serological indicators of coeliac disease that correlated with intestinal biopsy among high-risk Sudanese children. From July 2001 to July 2002, 80 children aged 15 months-18 years presented with poor appetite, weight loss, pallor and proximal muscle wasting. We diagnosed coeliac disease in 18 (22.5%). Antigliadin antibodies (AGA-IgG, AGA-IgA or both) were high in 44; endomysial antibody retest was high in 30. Guardians of 12 children refused consent for biopsy. The other 18 were biopsied: 5 had total villous atrophy, 8 subtotal and 5 partial. All improved with gluten-free diet. Degree of villous atrophy did not correlate with diarrhoea duration or severity, anaemia severity or serological titres. PMID- 17333798 TI - Diabetes knowledge, beliefs and practices among people with diabetes attending a university hospital in Karachi, Pakistan. AB - A structured questionnaire on knowledge, beliefs and practices regarding diabetes was administered to 199 persons with diabetes (92.5% type 2) attending the Aga Khan University Hospital, Karachi. Mean age [standard deviation (SD)] was 53 (11) years. Mean duration of diabetes (SD) was 8 (7) years in men and 9 (6) years in women. Men had a significantly better knowledge score than women (P = 0.02); there was no significant difference in the beliefs and practices scores. Scores were classed as good (> 60%) in only 13.6% of participants for knowledge, 17.6% for beliefs and 11.2% for practices. About 38% of the participants had received education on diabetes care. PMID- 17333799 TI - Profile of breast lesions among women with positive biopsy findings in Yemen. AB - This study described the profile of breast pathology based on records from a reference histopathology laboratory in Yemen of 773 women with positive biopsy or mastectomy findings. Cancers were classified according to the International classification of diseases for oncology. Benign lesions were found in 79.9% of cases. Fibroadenoma was the most prevalent lesion (30.0%) with a mean age at presentation of 22.2 years, followed by fibrocystic disease (27.4%) and breast inflammation (13.1%). Invasive carcinoma was found in 155 cases (20.1%), at a mean age of 44.7 years. PMID- 17333800 TI - Termination of second and early third trimester pregnancy: comparison of 3 methods. AB - The efficacy and safety of 3 methods used in legal termination of pregnancy in the second and early third trimester was assessed in 258 women in Jordan randomly assigned to receive Foley catheter (with and without traction) or prostaglandin E2 vaginal tablets. The failure rate of termination and the total insertion-to termination time was higher with Foley catheter without traction (16.5%, 16.5 hours) than with traction (10.0%, 14.2 hours) or prostaglandin (8.0%, 11.5 hours). However, Foley catheter as a method of termination of pregnancy in second and early third trimester is safe and inexpensive, and its efficacy can be enhanced with the use of traction to give similar results to prostaglandin E2. PMID- 17333801 TI - Variation in repeat caesarean section complication rates among 3 hospitals in northern Jordan. AB - We investigated the complication rates of repeat caesarean deliveries in 3 hospitals (national health, military, university) in Irbid by examining the obstetric records of 989 women from 1 December 1999 to 30 March 2004. There was a statistically significant difference between the number of previous caesarean sections and hospital. In total, 579 (58.5%) patients underwent elective caesarean section. There were statistically significant differences between hospitals for "failure to progress in labour" and "other" indications for caesarean section. After adjusting for the number of caesarean sections, regression analysis revealed that women from the military and university hospitals were more likely to have placenta praevia. There were no statistically significant differences between hospitals as regards post-operative complications. PMID- 17333802 TI - Fattening practices among Moroccan Saharawi women. AB - To study obesity in Moroccan Saharawi culture, 249 women were questioned about their desired body size and diet practices. The majority of women (90.4%) reported wanting to gain weight currently or at some time in the past. To gain weight, women used a fattening period (tablah) of at least 40 days of overeating with a reduction of physical activity and special traditional meals. Appetite enhancers (therapeutic drugs or fenugreek) and traditional suppositories were also used. Some women used corticosteroids to gain weight rapidly. The study highlights the need for health education about the dangers of obesity and steroid use in this culture. PMID- 17333803 TI - Effect of 5 years of dental studies on the oral health of Tunisian dental students. AB - This study is a follow-up of one made in 1998-99 on first-year dental students in Monastir. Now in their fifth year, we assessed the effect of dental studies on students' oral health practices and dental health. Of the 155 students in the first study, 140 were still enrolled. Periodontal troubles, malocclusion and dental decay affected 84.3%, 80.0% and 43.0% of the students respectively. Compared with the previous study, students had achieved a better dental health status--tooth brushing rate was much higher, prevalence of dental decay and periodontal pockets had decreased, and DMF index had improved. However, the prevalence of smoking, bleeding and calculus had not changed, and the frequency of malocclusion had increased. PMID- 17333804 TI - Dimensional accuracy of 3 silicone dental impression materials. AB - This study was carried out to measure the dimensional changes in silicone impression material, which can affect the fitness of the prosthesis. Using both single and double mix techniques, 20 impression samples for each of 3 different proprietary silicones, Xantopren-H, President and Fulldent, were made. Selected measurements were made on the stone casts made from each impression. In all 3 cases, the single mix gave more accurate casts than the double mix technique. The Xantopren-H impressions had the most accurate dimensions. PMID- 17333805 TI - [Occupational safety of cleaning personnel in Palestinian district hospitals]. AB - This study examined occupational safety among cleaning workers in Palestinian hospitals and its relation with the medical waste management in these hospitals. The level of occupational safety was below standard requirements, as protective equipment and clothes are not available for most workers. Over 40% of workers had been pricked with needles while handling medical waste. There was no clear policy for vaccination of workers against infectious diseases and no medical examination for workers before or during employment. Only 37.2% were trained in handling medical waste and 23.2% were working 15 hours per day or more; 55.8% had spent 1 year or less in their work. PMID- 17333806 TI - Knowledge and practices of health care workers and medical students towards universal precautions in hospitals in Mazandaran Province. AB - This study investigated knowledge of and practices towards universal precautions among 540 health care workers and medical students in 2 university hospitals in Mazandaran Province, Islamic Republic of Iran. Only 65.8% and 90.0% staff in the 2 hospitals and 53.5% of medical students had heard about universal precautions. Overall, there was a low understanding of precautions, except concerning disposal of sharps, contact with vaginal fluid, use of mask and gown or cleaning spilled blood. Health workers had difficulty distinguishing between deep body fluids and body secretions that are not considered infectious. Good practices were reported regarding hand-washing, disposal of needles, and glove, mask and gown usage. PMID- 17333807 TI - Job burnout in psychiatric and medical nurses in Isfahan, Islamic Republic of Iran. AB - By means of the Maslach Burnout Inventory, we examined job burnout among randomly selected nurses working on psychiatric (55 nurses) and medical units (51 nurses) at 2 university hospitals in Isfahan during 2003. Psychiatric nurses experienced a greater degree of emotional exhaustion than the medical nurses (P < 0.05). Significant positive correlation was noted between age, years of experience and frequency of on-calls and emotional exhaustion for the psychiatric nurses. Frequency of on-calls was also significantly associated with a sense of non accomplishment. Longer duration of service was accompanied by higher degree of emotional depersonalization for the medical nurses. PMID- 17333808 TI - Hospital financial performance in the United States of America: a follow-up study. AB - To clarify and validate the factors that influence hospital profitability in the United States of America, we used a cross-sectional design to examine data for 1998. Several changes and government regulations introduced in the early 1990s influenced hospital performance. We included those variables to give a better understanding of the hospital payment system. Among the explanatory variables considered, geographic location, competition, hospital size and occupancy rate were identified as the main contributors to hospital profitability. PMID- 17333809 TI - Alternative drugs against Trichomonas vaginalis. AB - To investigate the effect of drugs other than metronidazole, 3 non-pregnant women infected with Trichomonas vaginalis were treated with doxycycline, 2 x 200 mg/day for 1 week. Another 3 women were treated with praziquantel, single dose, 40 mg/kg body weight. No therapeutic effect was detected for either drug. In vitro, oxytetracycline led to death of T. vaginalis at a concentration of 15 mg in 0.5 mL medium. Extract of Myrtus communis caused death of T. vaginalis at pH 4.65, but failed to do so at pH 6.00. Extract of Eucalyptus comaldensis (50 mg in 0.1 mL medium) at pH 5.35 caused death of T. vaginalis after 24 hours. PMID- 17333810 TI - Hexadecyl-phosphorylcholine ointment for treatment of cutaneous leishmaniasis: an animal trial. AB - A placebo-controlled trial compared 6% hexadecyl-phosphorylcholine (HePC) and 12% benzethonium chloride ointment with placebo ointment for treatment of cutaneous leishmaniasis. Cutaneous lesions were experimentally induced by inoculation with leishmania promastigotes in 60 golden hamsters. Forty (40) animals were treated with drug and 20 with placebo ointment applied twice daily for 15 days. After treatment, all lesions were significantly reduced in size in the treatment group compared with the placebo ointment. No parasites were detected in smears from 35/40 of the drug-treated lesions and no relapses occurred over 120 days of observation. PMID- 17333811 TI - Urinary tract infection in infants and children with diarrhoea. AB - To determine when children with acute diarrhoea should be investigated for urinary tract infection (UTI), we studied 120 patients and 120 healthy age- and sex-matched controls aged 4 weeks to 5 years. In those with positive or suspicious urine cultures, bacteriuria or pyuria, urine culture was repeated. We detected UTI in 8 patients (all < 2 years) and 1 boy in the control group. In those with UTI, invasive diarrhoea was observed in 1, fever in 7 and vomiting in 5 patients. In children with acute diarrhoea, investigation for UTI is only recommended for febrile, female infants aged 5-15 months. PMID- 17333812 TI - Support for cancer patients: the Bahrain experience. AB - Cancer, a disease people avoid talking about, is the second leading cause of death in Bahrain. The Bahrain Cancer Society established a support group in 1993 with the goals of helping patients and their families cope with this disease and increasing public awareness concerning early detection. Services provided by the group include a weekly 2-hour session to encourage patients to express their feelings and concerns, distribution of informational booklets and visits to people at home and in hospital. Furthermore, the group organizes recreational activities for children with cancer. Patients or their families can also page the group to discuss their problems. The main goal of this paper is to share the Bahrain experience of supporting cancer patients, their families and friends. PMID- 17333813 TI - Muslim voices from the Eastern Mediterranean Region. PMID- 17333814 TI - Diabetic nephropathy. PMID- 17333815 TI - Risk factors for hypertension in UAE. PMID- 17333816 TI - International collaborative assessment study of the AHD575 method for the measurement of blood haemoglobin. AB - Accurate, economical methods for haemoglobin determination by laboratories in countries with limited resources are not available. This report provides the results of an international collaborative study evaluating the alkaline haematin detergent (AHD575) method as a reference method for laboratory services with limited resources. The study included 6 laboratories; 3 in East Mediterranean countries, 1 in East Africa and 3 in Europe. The (AHD575) method was evaluated against the HiCN method, with blood samples drawn from healthy and sick subjects. The results indicate that the AHD575 method is suitable for measuring haemoglobin in laboratories at all levels. PMID- 17333817 TI - Hepatitis B and C infection in first-time blood donors in Karachi--a possible subgroup for sentinel surveillance. AB - Hepatitis B virus (HBV) and C virus (HCV) are major public health concerns in Pakistan. We conducted a baseline analysis of first-time replacement blood donors at the blood bank of Jinnah Postgraduate Medical Centre in the year 2000 with the view to developing low-cost sentinel surveillance for these infections. Among 7325 such donors, 264 (3.6%) were positive for anti-HCV and 344 (4.7%) for HBsAg. HCV seroprevalence was significantly positively associated with age and lower education. Those speaking Sindhi or other minor languages had a significantly higher prevalence of HBV infection. Blood bank data could provide reliable information to monitor trends in prevalence of these infections. PMID- 17333818 TI - Bloodborne infections among student voluntary blood donors in Mansoura University, Egypt. AB - We carried out a retrospective study on student voluntary blood donors in Mansoura University, Egypt. Serum samples were tested for HBsAg, anti-HCV, anti HIV-1 and anti-HIV-2 as well as syphilis. About 7% of students had > 1 of the diseases tested for. Prevalence of HBsAg, anti-HCV, anti-HIV-1 and anti-HIV-2, and syphilis were 4.3%, 2.7%, 0.0% and 0.05% respectively. Significantly more males than females tested positive for HBsAg. Anti-HCV was significantly higher among rural than urban students. Volunteer student donors are a good source of safe blood. With proper selection of donors, the number of blood units discarded can be minimized. PMID- 17333819 TI - Hepatitis B prevalence among workers in Turkey at low risk for hepatitis B exposure. PMID- 17333820 TI - Informal health providers and the transmission of hepatitis C virus: pilot study in two Egyptian villages. AB - The roles and practices of informal health care providers were studied in 2 Egyptian villages, focusing on practices which might be associated with the bloodborne transmission of hepatitis C virus (HCV). In the study areas, many people resorted to male providers for injections, dentistry, wound treatment and male circumcision. Traditional birth attendants oversaw > 50% of all births. "Injectionists", barbers and staff at pharmacies performed services that may be associated with HCV transmission. These providers knew little about HCV, but were willing to learn. As villagers trust these providers and visit them even if primary health care facilities are accessible, efforts should be made to upgrade their practices in order to reduce the transmission of HCV. PMID- 17333821 TI - Personal hygiene and safety of governmental hospital staff in Shiraz, Islamic Republic of Iran. AB - Complying with infection control standards is essential to prevent nosocomial infections. We aimed to determine health workers' hygiene practices and compliance with recommended instructions for personal hygiene among staff in all 30 hospitals affiliated to Shiraz University of Medical Sciences. The results showed that physicians and nurses were less compliant with personal hygiene practices than cleaners. Availability of protective measures was better in teaching hospitals than nonteaching hospitals as were vaccination rates among staff (hepatitis B and tetanus/diphtheria) with physicians scoring highest. Measures are needed to improve health workers' compliance. PMID- 17333822 TI - Distinguishing between primary measles infection and vaccine failure reinfection by IgG avidity assay. AB - In this study in the Islamic Republic of Iran 365 measles cases were evaluated to distinguish between primary infection with measles and reinfection due to secondary vaccine failure. All cases previously confirmed by detection of specific IgM were tested for IgG avidity. A secondary immune response was seen in 18.4% of patients. All unvaccinated patients (16.7%) showed a primary immune response. Of 244 patients with documented vaccination, 75.8% showed a primary immune response and 24.2% showed a secondary immune response, thereby indicating a secondary vaccine failure. Almost all measles reinfections (99%) were seen in patients >10 years old, indicating that vaccination for 10-year-old children is recommended. PMID- 17333823 TI - Clinical and epidemiological features of severe malaria in children in four hospitals in Sudan. AB - We assessed the clinical and epidemiological features of severe malaria cases before admission, management in hospital and outcome and associated factors in 4 hospitals in different areas of Sudan over a 5-month period in 2000. There were 543 children admitted representing 21% of all paediatric admissions. Median age was 36 months. Treatment at home was the first action taken by 57.5% of families. Case fatality rate was 5/1000 and 93% of the children who died were under 9 years. Highest risk of death was associated with delay in seeking treatment and severity of illness before admission. Omdurman Hospital in Khartoum had the best case-management performance index compared to the other hospitals. PMID- 17333824 TI - Occurrence of enteropathogenic bacteria in children under 5 years with diarrhoea in south Tehran. AB - This study was carried out on 1600 rectal swabs from children under 5 years of age admitted at the health centre in Islamshahr, Tehran province, Islamic Republic of Iran, during 1998-99. The specimens were examined for various bacterial pathogens. Isolation rates were: enteropathogenic Escherichia coli 6.8%, Shigella spp. 3.4%, Salmonella spp. 2.9%, Campylobacter spp. 0.9%, Yersinia spp. 0.7%. The isolation rate was highest in the summer, except for Yersinia spp., which was predominantly isolated in spring. The results of this study demonstrate the significance of Yersinia spp. and Campylobacter spp. in patients with diarrhoea. PMID- 17333825 TI - [Retrospective study on the isolated strains of Salmonella in an Iranian hospital in Kermanshah]. AB - A survey of occurrence of Salmonella in blood and bone marrow cultures was conducted in 1989-1990 and 1999-2000 (Sina hospital, Kermanshah). A total of 496 (12.3%) and 60 (2.4%) Salmonella strains were isolated (from 4020 and 2447 cultures). In 1989-1990, the isolated strains were: S. typhi 448 (98.5%), S. paratyphi A 40 (8%), S. paratyphi B 5 (1%) and S. paratyphi C 3 (0.5%). In 1999 2000, the isolated strains were S. typhi 59 (98%) and S. paratyphi B 1 (1.5%). There was a 60.9% reduction in the number of specimens over the 2 periods. The rate of Salmonella isolation fell from 12.3% (1989-1990) to 2.4% (1999-2000). There was a 10.2, 8.3 and 6.6 times increase in resistance of S. typhi strains to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole respectively. PMID- 17333826 TI - Prevalence of anaemia in 2-12-year-old Iranian children. AB - Haemoglobin levels were used to estimate the prevalence of anaemia in children 2 12 years old in the Islamic Republic of Iran. The study was part of the National Health and Disease Survey in 1999 that used a cluster sample of 1 in 1000 of the Iranian population. Of 4170 children aged 2-6 years, 7.3% were diagnosed with mild anaemia, 2.5% moderate anaemia and 1.0% severe anaemia (WHO definitions). Of 8461 children aged 7-12 years, 10.9% were diagnosed with mild anaemia, 3.0% moderate anaemia and 1.1% severe anaemia. The prevalence of anaemia was significantly higher in rural than urban areas. PMID- 17333827 TI - Prevalence of migraine and tension-type headache in primary-school children in Shiraz. AB - From January to June 2003 we determined the prevalence of the various types of headache in 2226 schoolchildren in Shiraz (age 6-13 years) selected by multistage random sampling. Data were collected by questionnaire and clinical examination. International Headache Society criteria were used for diagnosis. The overall prevalence of headache was 31%. Prevalence rates of migraine and tension-type headache were 1.7% and 5.5% respectively. The prevalence of headache increased with age and girls were significantly more likely to report tensions-type headache. Positive family history of headache and abnormal sleep pattern were significantly associated with migraine. PMID- 17333828 TI - Familial Mediterranean fever in children: a single centre experience in Jordan. AB - Familial Mediterranean fever is quite prevalent among Arabs. We reviewed the files of 56 patients diagnosed with familial Mediterranean fever and followed up at King Hussein Medical Centre in Jordan over 4 years for their clinical profile, course, genotype, treatment and complications. There were 30 males and 26 females with a mean age at onset of 5.2 years. Abdominal pain (79%) was the commonest manifestation, followed by arthritis (13%) and chest pain (4%). Family history was positive in 50% of patients. Regarding treatment, 97% of patients responded well to colchicine, and amyloidosis was not documented in any patients after 5 years follow-up. The commonest genotype was M694 (64%), followed by heterozygous M694V-V726A (23%) and E148Q (8%). PMID- 17333829 TI - Home accidents in rural and urban areas of Shiraz, 2000-02. AB - Data on home accidents for a 3-year period (2000-2002) were collected from health houses, health centres and hospitals involved in a home accident prevention programme in Shiraz, Islamic Republic of Iran. A total of 15 402 accidents were registered, with a mortality rate of 1.3%. Accidents were more common in women than in men (52.1% versus 47.9%) and urban than rural areas (66.3% versus 33.7%). Burns (66.5%), followed by injuries due to sharp objects (11.3%) were the most common causes. Accidents were more prevalent in children aged under 5 years, followed by 5-9 and 15-19 years of age. PMID- 17333830 TI - Lung function reference values in Iranian adolescents. AB - There is insufficient information about reference values for pulmonary volumes for Iranian populations. A study of lung function parameters was made on 302 non smoking healthy Iranian students (152 male and 150 female). Lung function measures correlated strongly with height but not with body mass index. There were significant differences between some of the measured parameters and American Thoracic Society reference values for Caucasians (P < 0.05). Of note is the high functional residual capacity (110% higher) and low inspirational capacity (86% lower) in males compared with the reference values. PMID- 17333831 TI - Factors believed by Jordanian acne patients to affect their acne condition. AB - This study in Jordan described the pattern of acne in 166 untreated acne patients aged 13-42 years attending dermatology clinics and assessed patients' perceptions of factors that have an effect on their acne condition. Family history of acne was positive in 69.3% of acne patients. Emotional stress, hot weather and sweating were believed to be aggravating factors by acne patients of both sexes, and premenstrual factors and cosmetics were factors among women. Many acne patients believed that their acne was exacerbated by certain aspects of diet including nuts, chocolate, fatty food, fried food, eggs, cakes and biscuits, spices and coffee and tea. PMID- 17333832 TI - Misuse of topical corticosteroids: a clinical study in an Iraqi hospital. AB - We assessed the frequency of, reasons for and the most common dermatological problems resulting from misuse of topical corticosteroids. We used a questionnaire and skin examination to study patients presenting at the dermatological centre, AI-Sadr Teaching Hospital, Al-Najaf, Iraq during the period March 2001-April 2002. Of 1780 new patients, 140 (7.9%) had misused topical corticosteroids. About half were aged 10-19 years. Potent and highly potent preparations were the most commonly used. In 34.3% of cases, medical staff were responsible for prescribing/recommending the drugs. PMID- 17333833 TI - Prevalence and etiology of urinary stones in hospitalized patients in Baghdad. AB - Epidemiology and pathogenesis in urinary stones diagnosed in 184 patients were studied. Mean age was 38.3 years. Male to female ratio was 2.5:1. Stones were predominantly of mixed type: calcium oxalate was the commonest compound. Anatomical distribution of urinary stones was 67.4% renal, 12.5% ureteric and 14.6% bladder. Recurrence rate following previous surgical removal was 15.0%. Bacteria were isolated from 19 (24.4%) of 78 urinary stones: 14 were urea splitting and 5 non-urea splitting. Females had a greater chance of having infected stones. All bacteria isolated were sensitive to gentamicin and nalidixic acid. All isolates were resistant to amoxicillin and erythromycin. Multiple resistance to 6 antimicrobial agents was common (58.8%). PMID- 17333834 TI - Reproductive health knowledge, attitudes and practices of Iranian and Afghan men in Tehran Province. AB - This study was carried out in south-west Tehran province to assess the knowledge, attitudes and practices of men, Iranians and Afghan refugees, regarding reproductive health. A questionnaire was used for the assessment. Mean scores for knowledge, attitudes and practices for Iranians were 4.38/30, 13.89/20 and 12.99/31 respectively; for Afghans the scores were 3.79/30, 11.66/20 and 11.88/31. Although the scores in both groups were low, Afghans showed significantly lower scores for attitudes and practices. Access to reproductive health services was the same for both groups. Further scrutiny of men's role in reproductive health, particularly social and cultural factors, is strongly recommended. PMID- 17333835 TI - [Attitudes and opinions of Palestinian decision-makers about premarital examination law]. AB - We explored the attitudes and opinions of 90 Palestinian decision-makers about the draft law on premarital examination. The findings revealed that decision makers were aware of the spread of genetic diseases but not infectious diseases. The majority agreed on the draft law; however, they differed on the mode of its application. Half believed that the law is not ready yet for application due to insufficient financial support to establish the needed infrastructure. The most significant recommendations made by the decision-makers were to: enhance community awareness of the law, ensure proper coordination among the concerned ministries and institutions, and establish a national organization to work on endorsement of the tests and issuance of the appropriate application strategies and regulations. PMID- 17333836 TI - Towards establishing air quality guidelines for Pakistan. AB - While enforceable National Environmental Quality Standards for pollutants exist in Pakistan, ambient air quality guidelines have never been established. However, there is no reliable epidemiological/toxicological monitoring system in place in Pakistan to provide a basis for establishing guidelines for various air pollutants. This paper reviews the World Health Organization air quality guidelines as well as standards applied in countries of the Eastern Mediterranean and South-East Asia Regions. Based on these, and available data on the existing air pollution situation in Pakistan, national air quality guidelines are proposed for 6 major pollutants. PMID- 17333837 TI - Oral health-related quality of life: a broader perspective. AB - It is important to understand how people perceive the impact of oral diseases on their quality of life. Oral health-related quality of life (OHRQOL) is a relatively new but rapidly growing notion. The concept of OHRQOL is particularly significant to 3 areas - clinical practice of dentistry, dental research and dental education. There are different approaches to measure OHRQOL; the most popular one uses multiple item questionnaires. OHRQOL should be the basis for any oral health programme development. Moreover, research at the conceptual level is needed in countries where OHRQOL has not been previously assessed, including the Eastern Mediterranean countries. PMID- 17333838 TI - Photodynamic therapy as a new treatment of cutaneous leishmaniasis. AB - We assessed the effectiveness of photodynamic therapy in the treatment of cutaneous leishmaniasis in 5 patients. Delta-aminolevulinic acid in a water-in oil emulsion was applied to the lesions and irradiation was performed. The treatment was repeated once a week for a month. Each time, direct smears of the lesions were prepared and cultured in NNN media. In direct staining, smears showed no amastigotes after 1 or 2 sessions. Healing and cosmetic outcome after photodynamic therapy was excellent. Only mild local inflammatory reaction was noted with no scarring and 4 months after the last treatment session, there were no clinical signs of recurrence. PMID- 17333839 TI - Primary and acquired drug resistance in childhood tuberculosis. AB - This study determined the resistance pattern of Mycobacterium tuberculosis to 4 first-line anti-tuberculosis drugs in children with pulmonary tuberculosis at the Iranian National Research Institute of Tuberculosis and Lung Diseases from 1999 to 2004. There were 350 children with positive cultures over the study period: 7 (2%) were resistant to at least one of the 4 anti-tuberculosis drugs. Primary resistance was detected in 4 cases and secondary resistance in 3 cases. Most cases (6) were among Afghan refugees. Resistance to rifampicin both in primary and secondary resistances was high, showing that children in the Islamic Republic of Iran face the threat of drug-resistant tuberculosis transmission. PMID- 17333840 TI - Deficiencies in medical prescriptions in a Sudanese hospital. AB - We determined the quality of medical prescription in Ribat University Hospital, Khartoum through detecting errors in doctors' prescriptions. We randomly selected 1000 medical prescriptions and checked them for completeness and legibility. The total number of doctors responsible for writing the prescriptions was 46. The patient's full name was written on only 18.8% of prescriptions and that of the doctor on only 6.7%. In only 19.5% of prescriptions were drugs prescribed by their generic names, 59.7% lacked the quantity of the drug, 25.7% lacked the duration of treatment and 15.8% were difficult to read. The quality of drug prescriptions written by our hospital doctors is seriously deficient. PMID- 17333841 TI - Craniofacial war injuries. AB - In this paper, recent concepts in the management of war wounds of the maxillofacial region are described. A brief differentiation is also given between general practice medicine and military medicine. PMID- 17333842 TI - Perianal tuberculosis in an HIV-positive patient. PMID- 17333843 TI - Olibanum bezoar: complication of a traditional popular medicine. PMID- 17333844 TI - Announcement of the Sina Trauma Data Bank (STDB). PMID- 17333845 TI - Efficacy of paromomicin and gentamicin patches in the treatment of cutaneous leishmaniasis. PMID- 17333846 TI - Encouraging letters to the editor in EMHJ. PMID- 17333847 TI - [Sanitary service of girl guides during the 2nd World War]. AB - From the very beginning of the scout organization one of its main trends was the Samaritan service consisting in giving medical help to victims of disasters and acts of God. It became a domain of girls guide mainly. The articles describes a great commitment of the Polish girls guide in the medical assistance offered to their compatriots during the September campaign of 1939 and during the years of occupation from 1939 to 1945. It shows the education and training methods that prepared the girls to work with great dedication. From the first days of the war the girl guides started to work as nurses and orderlies in civil and military hospitals. They organized also their own hospitals and numerous first aid stations in bombed localities and roads frequented by fugitives escaping from the west parts of the country to the eastern territories. Under occupation, the girl guides organized their own underground medical service that collaborated strictly with military organization fighting for independence. Assisted by doctors they organized medical trainings for the members, collected medicines and sanitary materials, preparing themselves for the fights of the last part of the war. The girl guides organized groups of medical assistance of the National Army, which constituted a core of the organization medical service. During the "Storm" action several thousands of girls worked as orderlies that belonged to the combat troops of the National Army. The Warsaw insurrection was the greatest battle of soldiers of the National Army. The girls offered their help to thousands of soldiers and civilian victims. PMID- 17333848 TI - [Soviet politics of breaking international war law. Representatives of medical professions among the victims of the Katyn crime]. AB - In April 1940 the Soviet authorities murdered nearly 25 thousand Polish citizens belonging mainly to the intelligentsia. The crime is known as the Katyn Crime because Katyn was the first place where the victims had been discovered. Representatives of different medical specializations were one of the most numerous groups among the victims. Despite of the sixty-year period from their death the identity of many of them has not been found out. In the years 1994 - 1995 the author participated in exhumations made in the Katyn Woods. As an expert of the Government Board he was responsible for identifying, describing and cataloguing all objects found during the exhumation works. It was then when he started to gather information on medical doctors killed in 1940. The data verification has not been terminated yet as many of the data are incomplete and ambiguous. Publication of the partial and incomplete data is necessary to complete estimative information found in literature. The author considers that wider research works on the subject will deepen reflections on effects of the Katyn Crime. PMID- 17333849 TI - [The fight of the communist authorities with the Catholic Church in the health service in Poland (1945-1970)]. AB - The article shows the process of nationalization of Polish hospitals run by religious congregations and elimination of priests runs from medical care. The process lasted until resignation of Wladyslaw Gomulka from the post of the first secretary of the Polish United Worker's Party. We can distinguish two periods of the process: 1948-1953 of nationalized of the congregation hospitals and 1960 - 1970 when this presence of the Catholic Church in the health was limited to indispensable minimum. PMID- 17333850 TI - [A look on a half century of activity of the Wroclaw Division of the Polish Society of History of Medicine and Pharmacy]. AB - The Wroclaw division of the Polish Society of the History of Medicine was founded on 16th June 1957 as one of the seven branches of the Society. In its history one can distinguish three main stages of activity, comprising the years 1957-1972, 1976-1990 and since 1991 up to the present. In the years 1973-1976 some disagreements between the General Board of the Society and the local authorities of the Society led to a temporary break in its activity. The most frequently appearing issues during the meetings of the Society comprised first of all biographies of famous physicians since Renessaince up to the present, issues related to the history of medicine in the Lower Silesia and history of the Lvowian school of medicine, the so called nazi medicine as well as history of pharmacy. The members of the Wroclaw Division of the Society took part in numerous conferences both in the country and abroad. PMID- 17333851 TI - [The sick child in modern literature]. AB - The relationship between literature and medicine consists of many dimensions and has a long tradition--from antiquity up to the present, medicine itself has a literary or artistic nature, is both "art" (ars) and "science" (scientia), combines natural sciences and humanities. The whole world of medicine has been represented in literary texts. Literature has often taken the disease and therapy of children as their subject. These representations can be classified in eight dimensions: 1. pathophenomenology, 2. etiology, 3. subjectivity of the patient, 4. image of the physician, 5. diagnostics and therapy, 6. medical institution, 7. social reactions, 8. symbolism. Sickness and health of the child, in their natural and cultural breadth, remind medicine of its fundamentally scientific and humanistic nature. Health and disease are concerned with life and death, and are closely connected to the physical, social, psychic, and spiritual nature of humans. PMID- 17333852 TI - Mortality in eighteenth-century London: a new look at the bills. PMID- 17333853 TI - Out-patient maternity relief in late Georgian Buckinghamshire and Hertfordshire. PMID- 17333854 TI - [Wishes for recovery on bronze--comments on a coin in honour of L. Aelius Caesar]. AB - L. Aelius Caesar is a little known co-regent of Hadrian who, having already been taken ill, was elected Princeps as Hadrian's successor and died soon afterwards. The city of Mytilene in Lesbos dedicated a bronze coin for him while he was still alive. The reverse of the coin shows the arrival of Asclepios in the shape of a snake. It is certainly a reference to the mythic translation of the cult of Asclepios to Rome in the third century B. C. which introduced the worship of the healing god on the Tiber Island. The community of Mytilene that struck the coin wanted to wish the ruler, whose illness was generally known, a good recovery or even to encourage him to convalesce at the famous ancient spa of Mytilene. At the same time they wanted to make a request on their own behalf. They wanted to gain the favour of the putative successor to the ruling Princeps in order to keep or regain certain liberties for their city which have been reduced by Vespasian in his centralization of the Roman Empire. PMID- 17333855 TI - [Medical self-help in the writings of Ulrich Braker (1735-1798): the cultural and social resources of the "poor man of Tockenburg" analyzed with Pierre Bourdieu's capital concept]. AB - Living as a poor pietist spinner, weaver and cotton trader in the rural Toggenburg area in Eastern Switzerland in late eighteenth-century, self-help was central to Ulrich Braker's (1735-1798) reaction towards illness. Two initial examples exemplify this central position of self-help: Braker's cure from migraine in the year of 1784 and a quantitative analysis of his diaries. Based on the journals (which he maintained between 1768 and 1798) and Braker's autobiography this article scrutinizes the resources of self-help amongst the rural and poor population in the late eighteenth century. Methodologically, I am applying Pierre Bourdieu's capital theory to the analysis of Braker's writings. The paper first elaborates how self-help, i.e. self-treatment, drew upon a rich, vivid, and at times conflicting stock of "cultural capital" acquired in upbringing and through tradition, through a large scale of educated medical literature, and by personal experience. With regard to "social capital" it is then shown how Braker at times provided and achieved assistance within various direct or indirect, pre-existing or specifically on the purpose of self-help established relations (i.e. among family members, relatives, neighbors, friends and patrons, as well as acquaintances) as social resources. Finally the article demonstrates the interaction of self- and help from outside on multiple levels (either in the form of medical assistance or of poor relief). PMID- 17333856 TI - ["The main cause of his insanity, ... self-pollution". Attributions to illness and the treatment of insanity in the Siegburg Asylum (1825-1878). The case of Georg v. G]. AB - The 25 year old Georg v. G. is admitted to the respected Prussian Siegburg Asylum in 1835. After six years he is discharged from the Siegburg having been diagnosed "incurably insane". In search of possible causes for the illness, the participants involved in the discussion, his father, doctors and the clergyman, come to the conclusion that it is his continuous "self-pollution" that is to be blamed. Their opinion runs in accordance with the discourse within the medical profession that "self-pollution" among young men is a prominent cause of insanity. The young man's patient record makes it possible to reconstruct the forms of "therapy" which are undertaken to cure his feeble state and to keep Georg from his dangerous habit. His record elucidates the interplay between medical theory and medical treatment. The methods of treatment undertaken in the asylum intended to bring Georg back to reason which includes a disciplined behaviour. His case record also opens up new possibilities for research in the history of psychiatry, as, in contrast to previous results, this patient neither attributed his state to his "immoral" behaviour, nor did he take any notice of the attempts his surroundings underwent to prevent him from continuing his actions. PMID- 17333857 TI - [Curing by cutting. Surgical patients in the consulting correspondence of Lorenz Heister (1683-1758)]. AB - The consultation letters of Lorenz Heister (1683-1758) are kept in the University Library Erlangen-Nurnberg. Heister was not only a famous physician, but also a renowned surgeon. This double qualification gave a unique character to this correspondence: The letters allow not only a glimpse on the phenomena of "medicine-by-post", but of "surgery-by-post" as well. To those "surgical patients by-post" belong four men and one woman presented in this study. All of them suffered from a surgical treatable malady, but their decision for or against the surgical therapy was strikingly different, ranging from definite refusal to ardent desire. In spite of their inhomogeneous attitude towards the prospect of a surgical intervention, however, they had one feature in common: they decided by themselves. The frequently cited "informed consent" of our days was a matter of course with the patients of Heister's time. PMID- 17333858 TI - [The Wurzburg pharmakopoeias of the 18th and 19th centuries. New cognitions about the really published editions]. AB - Up to now the history of the Wurzburg pharmakopoeias was treated only cursorily. Solely the 'Wurzburg book of medicines [from Ortolf]' of the 13th century has been treated often. But also the definition of the term "pharmacopoeia" is not uniformly used. Four of the seven Wurzburg pharmacopoeias (pretendedly edited in 1777, 1778, 1782, 1796, 1807, 1813, and 1845) named in standard works could be eliminated as not published: the alleged editions of the 'Pharmacopoea Wirceburgensis' of 1777 and 1778, the 'Pharmacopoeia for poor people' from 1807 and the 'Military Pharmacopeia' from 1845. On the other hand two issues up to now not been registered were now newly determined: the second edition of the 'Pharmacopoea Herbipolitana' of 1782 (B), and the second edition of the 'Military Pharmacopoeia' (first edition 1813) of 1815. The author of the 'Pharmacopoea Herbipolitana/Wirceburgensis' was Franz Heinrich Meinolf Wilhelm (1725-1794), professor of medicine at the Wurzburg University; the authors of the 'Military Pharmacopoeia' were Joseph Herrmann Brunninghausen (1761-1834), professor of surgery at the Wurzburg University, and surgeon-general of the medical corps, and Johann Anton Hofmann (died 1844), military pharmacist. PMID- 17333859 TI - [Trepanation of the skull in classical antiquity]. AB - Archaeological findings prove that cranial operations of different techniques performed on living men, women, and children have a history of 7000 years. It is often assumed, that many of these operations were carried out for reasons, that are to be found in the realm of magic or, in the case of epilepsia, to drive the evil spirit out of the head. However, study of medical literature from classical antiquity proves that in those days medical doctors had a good knowledge of severe head injuries, as a result of their precise observation of injured or sick human beings. Consequently, there were a number of accurate medical diagnoses indicating cranial operations such as: severe fractures of the skull where cranial bones pressed upon the brain, haemorrhages between cranial bones and dura mater as well as osteomyelitis. The primary reason of surgical treatment of the latter was remove necrotic osseous tissue and not to trepan the skull. With the help of the surgical instruments found in Bingen and on the basis of sources from classical antiquity, the trepanation method as applied 2000 years ago may be explained in detail. Healing processes of skulls of people who underwent surgical treatment show that in an era where anaesthesia, asepsis and antibiotics were still unknown, approximately 80 per cent of patients survived the operation, provided that the highly elastic dura mater was not damaged either by the traumatic event or during surgery. An intact dura mater was the most important protection against infections which inevitably led to death in those times. PMID- 17333860 TI - [How did the castratos sing? Historical observations]. AB - Historical observations In Church music from the early beginnings to the 19th century, women were not allowed to sing, because of a wrongly interpreted quote of the Apostle Paul. Paul had ordered women to keep silence in ecclesia, it means: in the community and in the congregation, but he himself never mentioned a ban on singing in church. The castratos gradually replaced the men singing falsetto due to the latter's weaker singing performance from the 17th century onwards. They originated mostly from simple social backgrounds. Many poor families in Italy in the 17th and 18th centuries had up to 15 children and there was far too little work for the population. Some castratos were the stars of the opera. But as human beings they were discriminated. The castration took place mostly between the 7th and 12th years of their lives and many died as a result of the operation. The singing-lessons thereafter lasted 5-6 years. In the 18th century, the most famous castrato was Carlo Broschi, named Farinelli (1705-1782). Numerous arias sung by him are still in existence as scores, some are high quality concert pieces. There are modem versions on CD sung by a counter-tenor or a mezzo-soprano as soloists. Farinelli was able, during a visit to Spain, to improve with his singing the mood of two severely depressive kings. In the late 18th and in the 19th century, the castratos were increasingly replaced by tenors and women singers. The only historical sound recordings were sung by one of the last castratos, Alessandro Moreschi (1858-1922). The recordings were made in 1902 and 1904 in the Vatican. The arias are in the style of the end of the 19th century and contain no longer anything of the bravura arias so admired by the audiences in the 18th century. Since the end of World War II, the high male voices have experienced a renaissance. PMID- 17333861 TI - [Possibilities and limits of retrospective diagnoses. Pathobiografical notes on Wolfgang Amadeus Mozart's diseases (1756-1791)]. AB - On December 5th, 1791, Wolfgang Amade Mozart died from an acute febrile disease which had been accompanied by painful tumefactions around his hands and feet. The official diagnosis 'hitziges Frieselfieber' (severe military fever) cannot be decoded or translated into modern medical terms. Hypotheses which assert either a wilful or an erroneous poisoning with mercuric chloride have not been corroborated. Innumerable diverging retrospective diagnoses have been made by physicians during the 19th and 20th centuries. In this essay, we give a pathobiografical description of Mozart's three severe diseases from which he suffered as a boy: When traveling through Europe with his parents and his sister to give many exhausting concerts Wolfgang Amade fell ill with an Erythema nodosum (1762), an abdominal typhus (1765), and with smallpox (1767). With regard to the 24 years between 1767 and 1791, however, we don't have much evidence for the suspicion that Mozart has had severe acute or chronic diseases as a grown-up. He may have been physically robust, but mentally he was rather sensitive. In his letters, Mozart sometimes portrayed a temporary bad state of health in order to illustrate his inconvenient emotional and/or financial situation. Up to November 18, 1791, Mozart's creativity was unbroken. His death came unexpectedly after an illness of 15 days. PMID- 17333862 TI - [The history of trophoneurosis with special regard to Moritz Heinrich Romberg (1795-1873) and the hemiatrophia]. AB - The creation of the class trophoneurosis is owing to Romberg as well as to Henoch and Canstatt. The optional classification is based upon the general scientific basis of a correlation between form and function, also supported by a neurology upswing which, among other things, entailed the settlement of several nerval functions. The long history of this class, in spite of inadequate experimental background, can be explained by means of Romberg's authority combined with the vague reception plus a lacking clearness of Romberg's comments. Any influences of older theories of a nourishing fluid inside the nervous tube could not be proved. It is safe to assume that this theory was overcome with the discovery of the electricity as a transition modus in the mid-19th-century. PMID- 17333863 TI - [The Rostock chair of pharmacology under Paul Trendelenburg 1919-1923]. AB - On May 15th 1919 the pharmacologist Paul Trendelenburg, son of the surgeon Friedrich Trendelenburg, was appointed head of the Department of Pharmacology and Physiological Chemistry at the University of Rostock. Though these days still saw the aftermath of World War I, faculty and administrational procedures were pursued in a surprisingly rapid and concise manner, so that less than two months were needed for the appointment. Despite the scarcity of funds and serious postwar inflation, Trendelenburg soon embarked on an ambitious experimental and publicational program, his methodology firmly resting on the physiological basis of any pharmacological finding. The Rostock years mark the completion of his work on adrenaline, he had started earlier when refining the preparation of the perfused frog hindquarters (the Trendelenburg preparation) in Walther Straub's laboratory at Freiburg i. Br. Trendelenburg's vigour and scientific productivity during his 4 years at Rostock can be easily inferred from his almost 400 pages of extensive reviews, separating facts from fiction. Rostock marks as well the beginning of his work on hormones. Trendelenburg's endocrinological work stands out for the development of sensitive bioassays for measuring calcium concentrations after thyroidectomy and for evaluating the oxytocic principle of the posterior lobe of the pituitary gland which not only made him alert the pharmaceutical industry to the insufficient quality of pituitary extracts on the market, but also led him to discover the principle of neurosecretion within the tuber cinereum of the hypothalamus. PMID- 17333864 TI - [Julius Ludwig August Koch (1841-1908). Psychiatrist, philosopher, and Christian]. AB - Julius Ludwig August Koch was born 1841 in the small town of Laichingen (Wurttemberg) in the Southwest of Germany. After working as a chemist for about seven years, he studied medicine in Tubingen from 1863 to 1867. First he worked as a physican and later in a private mental hospital in Goppingen. From 1874 to 1898, he was director of a state mental hospital in Zwiefalten (Wurttemberg). Koch died in 1908 after a long period of suffering in Zwiefalten. Being deeply routed in a Christian faith and having much interest in moral and ethical issues, Koch published some philosophical works 'Epistomological investigations' (Erkenntnistheoretische Untersuchungen, 1882), 'Outline of philosophy' (Grundriss der Philosophie, 1885) and 'Reality and its knowledge' (Die Wirklichkeit und ihre Erkenntnis, 1886). In this papers he tried to bring together critical Kantian philosophy and Christian conviction. In 1888 he published a 'Short Textbook of Psychiatry' (Kurzgefasster Leitfaden der Psychiatrie), where he mentioned the term "psychopathic inferiority" for the first time (Psychopathische Minderwertigkeiten). The following work, focussing on this issue with the title 'Psychopathic Inferiority' (Die psychopathischen Minderwertigkeiten, 1891-1893), became one of the fundamental texts concerning the concept of disorders of personality, which are in use today. In this book, published in three parts, he tried to describe the hole field between psychic normality and psychoses. Only the first and biggest part deals with psychopathological symptoms which we now think to be essential for personality disorders. Koch differentiates between "disposition" (Disposition), "burden" (Belastung) and "degeneration" (Degeneration), assuming a graduation. "Disposition" should be the mildest disorder, turning into normality, whereas "degeneration" turns to psychosis. Koch believed, that on the basis of all degrees of "psychpathic inferiority" there was a congenital defect of the constitution of the brain. To be consistent, he demanded that the individuals in question should not be punished as hard as people without this disorder by the courts, and proposed to open up special institutions beside the usual prisons. Beside this, Koch describes in the other parts of his book vividly for example acute and chronical organic psychoses and obsessions. Although psychiatric disorders are classified different today, Kochs work keeps its great importance for the concept of personality disorders, further more one can find very exact and detailed descriptions of a multitude of psychpathological symptoms, which are worth reading them today. PMID- 17333865 TI - [The surgeon Georg Raeschke (1884-1963)--a German fate]. AB - George Raeschke M. D. is a forgotten famous surgeon, gynaecologist and orthopaedist of the 20th century in Thuringia. His life and work appears as a mirror of the development of surgery and of the political force in Germany--with the rise in the "golden twenties" and the fall in the second world war. The great tragedy of the family Raeschke happened when three from four sons were killed in action at war respectively at the frontier between American and Russian zone. Likewise fateful and negative proved the communist regime in GDR which forbid a private medicine and did not permit to take over the private hospital. Therefore the last son, a surgeon too, fled from GDR. The clinic in Muehlhausen/Thuringia was nationalized, later transformed in a childrens hospital. Today--back in private hand--the building accommodate a home for old people with medical care. PMID- 17333866 TI - [Mortality in Nuremberg in the 19th century (about 1800 to 1913)]. AB - Before the middle of the 19th century urban life was hazardous, life expectancy in big cities was shorter than in the countryside, it was half as high as it is today. Cities used to be called "the graves of mankind"; they were unhygienic, since their inhabitants lived under crowded, unhealthy conditions. In German cities infant mortality was extremely high, one out of three new-born children died within its first year. In most big cities more people died in any given year than were born. In 1806, when the Imperial City of Nuremberg was absorbed by the Kingdom of Bavaria, it had 25 000 inhabitants, fewer than around the year 1600. In the following decades Nuremberg grew quickly, up to 50000 in 1846 and 100000 in 1881, 330000 in 1910. Its population was living extremely crowded within the medieval city-walls, up to 58 000 (1885) in the old parts of the city, more than twice as many as in 1806. Mortality was bound to increase, as more and more people moved to Nuremberg. Mortality rose from 25.5 per thousand in the 1820's to 29.4 in the 1850's and 32.8 in the 1860's. This increase of population was mainly due to migration from outside, from the countryside. New industries settled down in Nuremberg and provided new jobs, the new factories produced lots of smoke and dangerous dust. The general living conditions of the workers were poor, people were much smaller than nowadays. During the industrialisation labor was backbreaking, working hours were extremely long, and annual working hours were more than twice as long as today. New and better legislation was written by the Northern German Confederation, founded in 1867. Now the magistrate of Nuremberg recognised that something had to be done. In the following years physicians began to collect information as to morbidity and mortality in various parts of Nuremberg. Very many people still died of infectious diseases, esp. of tubercolosis, typhoid fever, diphtheria, pertussis, scarlet fever and other infectious diseases. There were many cases of bronchitis and deadly pneumonia. Even suicide was an important cause of death. In 1886 mortality at Nuremberg peaked for the last time above 30. Nuremberg had fewer doctors than other big cities in Germany. The city-fathers noticed that the public wells and the drinking water were dirty--they were getting more and more contaminated as time went by. It proved extremely difficult to provide this fast growing population with "free goods" like clean water and air. In the 1870's Nuremberg began to build a new water supply and a modern municipal sewer system. Cases of typhoid fever declined quickly thereafter. The magistrate did not provide new apartment houses, but it took care that the new houses were more hygienic, with toilets and other necessary facilities. After 1880 new vaccinations were developed by modern medicine, these and other methods of preventive medicin proved to be more important for prolonging human lifes than therapeutic medicine. In the 1880's a steep rise of income can be registered, it brought more and better food, more meat, and better living and working conditions--and fewer working-hours per year. At the eve of World War I, Nuremberg was one of the ten or twelve biggest cities in Germany, an industrialized city with a hard-working population, people with little education and income. Urban mortality in Nuremberg declined rather slowly. In 1867 35.7 percent of all deceased persons were infants, less than one year old, in 1913 that percentage had declined to 30.7. In 1867 only 9.3 per cent of the deceased were older than 70, in 1913 the elderly constituted 14.2 per cent. Very many people still died in their forties or fifties. PMID- 17333867 TI - [Consolation as medical intervention and its history of ideas]. AB - A review of interpretations of "suffering" was presented after an etymological clarification of the term "consolation". The review begins with an examination of concepts of consolation in the early Greek and Roman antiquity continues with late Greek and Roman antiquity, the early and late Middle Ages, the epochs of Humanism and Reformation and the time after Reformation until to the present. Concerning concepts of consolation in the present the conception of the movement "Biblical Therapeutic Pastoral Care", Viktor Frankl's "Logotherapy" and Viktor Emil von Gebsattel's "Anthropologic Psychotherapy" are discussed. Finally, some essential features of general conceptions of consolation are presented. PMID- 17333868 TI - Poor KSF progress puts careers at risk. PMID- 17333869 TI - 'The programme portrays nursing as an endless string of isolated manual tasks'. PMID- 17333870 TI - What's next for students? PMID- 17333871 TI - A lifeline for teenagers. PMID- 17333872 TI - Inequality and infant mortality. AB - The government has a target to achieve a 10% reduction in inequalities in health outcomes by 2010 as measured by infant mortality and life expectancy at birth. The Department of Health has carried out a review of progress due to concerns that while the infant mortality rate in England is at an all-time low, the gap between different social groups remains. The review found the gap has widened. This article outlines the results of the review and the actions healthcare professionals can take to help reduce health inequalities. PMID- 17333873 TI - Skeletal system: part four--the appendicular skeleton. AB - The final article of this four-part series explores the appendicular skeleton. The term 'appendicular skeleton' derives from the Latin word appendic--to hang on. The appendicular skeleton consists of the four limbs and the pectoral (shoulder) and pelvic girdles, which connect them to the axial skeleton (see part 3 of this series; Docherty, 2007). It has a total of 126 bones. PMID- 17333874 TI - Use of tens in pain management: part two--how to use tens. AB - Transcutaneous electrical nerve stimulation is widely used in pain management but its effectiveness depends on the stimulation being targeted appropriately. This article, the second in a two-part series, outlines how to set up and use a TENS machine to achieve the most effective results. PMID- 17333875 TI - Tuberculosis treatment: managing non-adherence. PMID- 17333876 TI - A guide to regulation of blood gases: part three. AB - In the third and final part of this series looking at blood gas analysis, Liz Allibone and Nicola Nation provide three examples of how arterial blood gas results assist in the diagnosis and management of illness. PMID- 17333877 TI - Nurse-led arterial blood gas sampling for patients. AB - Following the introduction of new guidelines in February 2006, assessments for long-term oxygen therapy are now being undertaken by respiratory nurse specialists. The key skill required is arterial blood gas sampling. This has traditionally been the role of the doctor, however by using an education and training package along with a competency-based assessment, nurses can now perform this extended role. Sarah Dodds and Graham Williamson describe a competency-based education and training programme for nurses to carry out this procedure. PMID- 17333878 TI - [The herbals and floristic albums of Eliza Orzeszkowa]. AB - In many of her literary works, the writer and columnist Eliza Orzeszkowa (1841 1910), who was twice nominated for the Nobel Prize in literature (1905, 1909), depicted the life of the Polish society in the eastern lands of the former Polish Lithuanian Commonwealth in the second half of the 19th century. A great lover of nature, Orzeszkowa appreciated the botanical knowledge of the local rural population in the vicinities of Grodno. She combined attempts to master that knowledge with her other great passion, that of investigating folk culture, and was always ready to listen to what women who were village herbalists had to tell her about medicinal plants, and about the customs and legends connected with the medical practices based on herbal remedies. She then passed on the information to botanists for scientific verification. Orzeszkowa's naturalist and ethnographic fascinations led her to write a cycle of articles on "The people and flowers on the Niemen river", published in 1888-1891 in the ethnographic-tourist magazine "Wisla". This collection of articles has been analysed not only by historians of literature, but also, since 1985, by historians of science. The first analysis was conducted at the Section for the History of Pharmacy of the Institute of the History of Science of the Polish Academy of Sciences. This yielded Ewa Kaminska's study: Zioloznawstwo i ziololecznictwo w publikacjach etnograficznych Elizy Orzeszkowej [The knowledge of herbs and medicine based on herbal remedies in the ethnographic publications of Eliza Orzeszkowa] published as part of the Institute's Historia lekow naturalnych [History of natural medicines], ed. Barbara Kuznicka, vol. I: Zrodla do dziejow etnofarmacji polskiej [Sources for the history of Polish ethnopharmacy], Warszawa 1996, pp.25-88. The subject-matter of the publication aroused much interest among historians of pharmacy from Poznan. The first sign of that interest could be seen in the article by Jan Majewski and Slawoj Kucharski entitled Pasje pisarki [The writer's passions], published in 1998 in "Gazeta Farmaceutyczna" [Pharmaceutical Journal] and illustrated with pages from the herbal created by Orzeszkowa. One of the authors, Jan Majewski, has found also other herbal-albums, kept, among other places, at the Museum of the Marist Fathers near London, and in the archival collections of the Ossolineum publishing house. A major surprise was connected with the discovery of a herbal that had the features of genuine botanical documentation. The title page of the herbal, which was discovered (by Jan Majewski and Slawoj Kucharski ) at Poznan, in the collections of the Poznan Society of the Friends of Science, carries the inscription: Zielnik Elizy Orzeszkowej. Z pol, lak i lasow, nadniemenskich miejscowosci, Miniewicze, Ponizany, Hledowicze, Kowszow, Poniemun, Horny, Kolpaki [The Herbal of Eliza Orzeszkowa. From the fields, meadows and woods of localities on the Niemen river, Miniewicze, Ponizany, Hledowicze, Kowszow, Poniemun, Horny, Kolpaki]. The value of the herbal for the history of botany has been appreciated by Anna Maria Kielak, the author of a beautiful bibliophile publication entitled Zielnik Elizy Orzeszkowej nieznany zabytek botaniczny przechowywany w zbiorach Poznanskiego Towarzystwa Przyjaciol Nauk. [The herbal of Eliza Orzeszkowa. An unknown botanical aabytek kept in the collections of the Poznan Society of the Friends of Science], Poznan 2004, pp. 151. The author has presented Eliza Orzeszkowa's biography, as well as her botanical and ethnographic passions. She has also made a list of the plants mentioned in the herbal, as well as appendices containing Orzeszkowa's correspondence with botanists. The author also describes the artistic albums composed by Orzeszkowa from dried herbs. PMID- 17333879 TI - [Assemblies of the medical circles of the Kingdom of Poland. 1908-1914]. AB - Assemblies of the medical circles of the Kingdom of Poland in the years 1908 - 1914 were a kind of reflexion for their activity both in undertaking and attempting at solving the contemporary salubrious problems of the country. An idea of organizing the cyclical meetings was initiated by two of the biggest centres--Warsaw and Lodz. Within first of the centres there appeared a conception of organizing the hygienists' assemblies, and within second one--an idea of the conferences for provincial doctors and apothecaries. Organization and realization of the medical circles' assemblies in the Kingdom of Poland was possible thanks to the activity and committal of the societies that also came from outside the centres being the main ventures' organizers. In general, there were organized seven provincial assemblies. Within this number four of the assemblies were organized by the hygienists, two--by the doctors, and one--by the apothecaries. Predominatingly the ventures' organizers were: Lublin i Lodz (twice), and once: Czestochowa, Wloclawek and Kalisz. None of the provincial assemblies took place in Warsaw. This fact stayed in accordance with the initiators' ideas that indicated the need for activating the smaller centres. The assemblies drew an attention and interest of the medical circles. Among others, it can be testified with a great attendance of the representatives that came not only from different centres of the Kingdom of Poland, but also--to a low degree--from other territories of the Russian, Galician and Poznan sector. Subject matter, which was undertaken during the meetings, was widely discussed both in the columns of the professional periodicals and the local press. PMID- 17333880 TI - [Analytical model for the transmembrane voltage induced on a permeabilized cell membrane in suspensions exposed to DC pulse fields]. AB - During the electroporation cell membrane conductivity increases dramatically, so the analytical model for calculating the transmembrane voltage (TMV) induced on an unpermeabilized cell membrane in suspensions can not be used in this case. An analytical model for the TMV induced on a permeabilized cell membrane in suspensions exposed to a high voltage DC pulse field was built. First, a permeabilized cell was replaced by a sphere cell having the equivalent conductivity. Then the average field inside the permeabilized cell suspensions was calculated according to the effective medium theory. Finally, based on the analytical solution for the TMV on a single unpermeabilized cell, an analytical model for the TMV on a permeabilized cell in suspensions was derived. The model shows that the TMV depends on parameters such as the external electric field, critical angle of electroporation, cell radium, conductivity of the cytoplasm, membrane and external medium, cell arrangement and cell volume fraction. PMID- 17333881 TI - [Image processing applying in analysis of motion features of cultured cardiac myocyte in rat]. AB - Study of mechanism of medicine actions, by quantitative analysis of cultured cardiac myocyte, is one of the cutting edge researches in myocyte dynamics and molecular biology. The characteristics of cardiac myocyte auto-beating without external stimulation make the research sense. Research of the morphology and cardiac myocyte motion using image analysis can reveal the fundamental mechanism of medical actions, increase the accuracy of medicine filtering, and design the optimal formula of medicine for best medical treatments. A system of hardware and software has been built with complete sets of functions including living cardiac myocyte image acquisition, image processing, motion image analysis, and image recognition. In this paper, theories and approaches are introduced for analysis of living cardiac myocyte motion images and implementing quantitative analysis of cardiac myocyte features. A motion estimation algorithm is used for motion vector detection of particular points and amplitude and frequency detection of a cardiac myocyte. Beatings of cardiac myocytes are sometimes very small. In such case, it is difficult to detect the motion vectors from the particular points in a time sequence of images. For this reason, an image correlation theory is employed to detect the beating frequencies. Active contour algorithm in terms of energy function is proposed to approximate the boundary and detect the changes of edge of myocyte. PMID- 17333882 TI - [Motion tracking of coronary vessel segment based on active contour model]. AB - An original method for analyzing two-dimensional motion of coronary arteries from X-ray angiogram sequences based on active contour model (snake) is presented. The convergence result of the snake in previous frame is used as the initial guess in current frame. Centerlines of interesting vessel segments at successive time instants can be detected through snake deforming from its initial position to optimal position by minimizing the proper energy function. Measurement of intensity similarity between consecutive frames is encompassed into the energy function to obtain accurate tracking. The effectiveness of the method has been demonstrated on clinical coronary artery angiogram sequences and results are encouraging. PMID- 17333883 TI - [A semi-automatic method for tooth segmentation in dental CT images]. AB - To reconstruct a tooth model from CT slices, we need to define the accurate contour of each tooth from CT slices. In this paper, we propose a semi-automatic method for drawing the contours of teeth in dental CT images. First of all, we select the reference slice from CT slices and carry out tooth segmentation interactively based on shape characteristic of each tooth. The dental CT images have the following distinct characteristic: in two neighboring CT slices, the size, location and intensity of corresponding tooth is very similar, so we can project the bounding box of the tooth whose contour has been drawn onto the next slice as the operation region of corresponding tooth. And then we perform segmentation operation tooth by tooth in the operation region based on the region growing algorithm using the information passed from the previous slice. With the reference slice as the starting slice, we carry out tooth segmentation slice by slice like this way automatically. The test result shows that the proposed method can detect the contours of teeth quickly and reliably with only little user intervention and it has practical value. PMID- 17333884 TI - [ROC analysis and one of its applications to fMRI data]. AB - The purpose of this study is to show the basic principle of receiver operating characteristic (ROC). Some advantages of ROC were given. A simple ROC curve was made to explain the method of plotting. An example of ROC applied to fMRI data was displayed, which showed that ROC can be effectively used in fMRI data. PMID- 17333885 TI - [The experimental research on the frameless registration based on the digital subtraction angiography]. AB - In this paper, we present an experimental research on the frameless registration of DSA/CT images based on frameless localization algorithm. The result shows that, 3D fusion and registration of vessels in the DSA images and anatomical structures in CT images will help surgeons to make accurate diagnosis and on plann operative. PMID- 17333886 TI - [Further analysis and study based on a visualized method for SARS RNA sequences]. AB - This paper proposed a new kind of visualized method of genome. Using cellular automation theory, the visual method transfers one-dimensional RNA sequence into two-demension visual image. Applying this method to SARS RNA sequence analysis, the characteristic of SARS-CoV differing from Non-SARS is discovered. This paper extracts characteristic genome fragment, visualize them, and study them with some pattern recognition method such as PCA and SVM. The result shows that the characteristic of SARS-CoV is classifiable. Some combined methods can use the characteristic more sufficient as an un-routine method. PMID- 17333887 TI - [Medical image segmentation based on the minimum variation snake model]. AB - It is difficult for traditional parametric active contour (Snake) model to deal with automatic segmentation of weak edge medical image. After analyzing snake and geometric active contour model, a minimum variation snake model was proposed and successfully applied to weak edge medical image segmentation. This proposed model replaces constant force in the balloon snake model by variable force incorporating foreground and background two regions information. It drives curve to evolve with the criterion of the minimum variation of foreground and background two regions. Experiments and results have proved that the proposed model is robust to initial contours placements and can segment weak edge medical image automatically. Besides, the testing for segmentation on the noise medical image filtered by curvature flow filter, which preserves edge features, shows a significant effect. PMID- 17333888 TI - [Recognition of heart rate variability signal using fuzzy associative memory pattern classifier]. AB - We have designed the fuzzy associative memory pattern classifier (FAMPC) using multi-input and multi-output fuzzy set. It is adaptive to recognition of heart rate variability (HRV) signal, validity proved by many experiments. PMID- 17333889 TI - [Investigation of morphology and anatomic variations of circle of Willis and measurement of diameter of cerebral arteries by 3D-TOF angiography]. AB - To observe the morphology and anatomic variations of the circle of Willis and its clinical significance. To measure and establish the normal reference parameters of average diameters of its component vessels in the healthy Chinese by using 3D TOF MR angiograms and to determine whether age-or sex-related differences exists in the circle' anatomy. MRA was performed in 153 healthy subjects. According to its integrity, Willis'circle was divided into four types: (1) Type I, showing an intact circle. (2) Type II, having a complete anterior circulation but an incomplete posterior circulation. (3) Type III, having an incomplete anterior circulation but a complete posterior circulation. (4) Type IV, having an incomplete anterior and posterior circulation. Based on the development of the components of the circle, each type was subdivided into four subtypes: typical, variable, hypoplastic and mixed. The statistically significant differences were not found in each type or subtypes between the different age and sex groups. Result of 153 cases, Type I, II, III and IV was found in 53 (34.64%), 73 (47.71%), 8 (5.23%), and 19 (12.42%) respectively. The display rate of the anterior and the posterior communicating arteries was 87.58%o (134/153) and 65.34% (100/153) respectively. Display rate of fetaltype posterior cerebral artery(PCA) was 20.92%. 3D-TOF MR angiography has important clinical significance for evaluating morphology and anatomic variations of circle of Willis. The normal values of diameter of cerebral arteries on MR angiograms may play a reference role in diagnosing cerebral vascular diseases. PMID- 17333890 TI - [Time-frequency analysis of ventricular fibrillation and the effects of amiodarone]. AB - This study is to quantify time-varying dominant frequencies in electrocardiogram (ECG) during the ventricular fibrillation (VF). Orthogonal ECG (sagittal, x; transverse, y; and longitudinal, z) and the transvenous two-leads defibrillation systems were set in 19 dogs. Time-frequency analysis was used to assess changes in the dominant frequency within ECG recorded in dogs during trials of 10-30 s of VF. In 4 additional dogs, the dominant frequencies were compared during 10 s of VF before and after administration of amiodarone. Results showed that in the 427 trials of 10 s VF and 335 trials of 30 s VF, average variation in the dominant frequency was considerable, between +/- 12%-18%. The frequencies orthogonal ECG during 10 s VF were distributed symmetrically above and below the mean frequency like a normal distribution. In the 79 trials with administration of amiodarone during 10 s VF in all three ECG, the mean frequencies decreased from 6.5 (x), 7.4 (y) and 7.0 Hz (z) to 6.1, 6.4 and 6.3 Hz (P < 0.01), respectively, and the variation in dominant frequencies decreased from 1.18, 1.38 and 1.19 to 0.98, 1.11 and 1.02 Hz (P < 0.05) respectively. The results confirmed that the frequencies of 10-30 s VF in ECG vary considerably and continuously, and amiodarone decreases this variation. PMID- 17333891 TI - [Imaging technique and features of the 16-slice detector spiral CT for aortic lesions]. AB - The purpose of this study was to describe the 16-slice detector spiral computer tomography (SCT) technique and imaging features of aortic aneurysms. We analyzed 21 patients documented aortic aneurysms, that underwent unenhanced and contrast enhanced spiral CT with a 16-slice scanner (Sensation 16), and three-dimensional reconstructions were performed for CT scan images. The results showed that: (1) Aortic dissection (11 cases), included the true and false lumen (11 cases, 100%), intimal flaps (11 cases, 100%), intimal tear (9 cases, 81.8%) and thrombosed false lumen (5 cases, 45.5%); (2) Intramural hematoma, unenhanced CT depicted crescent-shaped areas with high attenuation extending along the walls of the aorta, no definable intimal flap, while contrast-enhanced CT showed no enhancement of attenuation in the crescent-shaped areas; (3) True aortic aneurysms (7 cases), CT revealed the size, range, thrombosis and calcification of all aneurysms; (4) Pseudoaneurysms (2 cases), the enhanced part of the inhomogeneous masses beside the aorta connected with the aorta shown on contrast enhanced CT. Therefore, 16-slice detector SCT axial and three-dimensional images can exactly reveal the pathological and anatomical features of aortic aneurysms, and provide detailed imaging information for clinical therapy. PMID- 17333892 TI - [Study of the adsorption behaviors of plasma proteins on the single-walled carbon nanotubes nonwoven]. AB - Single walled carbon nanotubes (SWNT) have attracted increasing research interests for the purpose of biomedical application because they provide not only nanostructured topography, but also chemical composition of pure carbon atoms, as well as ultra high strength and excellent flexibility. Regarding the interactions of nanomaterials to biological systems, non-specific adsorption of plasma proteins is one of the most important issues to be concerned, which plays a crucial role that would determine how biological systems response to the biomaterials. Motivated by application of SWNT materials in biomedical fields, in this study, the adsorption behaviors of plasma proteins on the surface of SWNT nonwoven, prepared directly by floating chemical vapor observation and energy deposition method were investigated by means of scanning electron microscope (SEM), dispersive X-ray (EDX) analysis and ELISA. Results indicated the SWNT non woven showed a clear adsorption preference of fibrinogen over albumin. There was no human serum albumin detected using above analysis methods on the SWNT nonwoven even incubated in the albumin solution of 4 mg/ml. While more than 0.15 microg of human fibrinogen was detected by ELISA on the SWNT nonwoven with area of 40 mm x 40 mm incubated in the fibrinogen solution of 5 microg/ml. In addition, IgG of sheep-anti-human serum fibrinogen exhibited strong nonspecific adsorption on the surface of SWNT nonwoven. The adsorption behaviors are different significantly from those of other carbon materials and conventional biomaterials. The unique interaction of SWNT nonwoven to plasma proteins is of significance to further studies of blood cells responses. PMID- 17333893 TI - [The effect of microencapsulated NGF-expressing NIH-3T3 cells on bioengineered dermis function in vitro]. AB - Nerve growth factor (NGF) can promote the regeneration of peripheral nerve as well as contraction and reepithelization of wound. We constructed a bioengineered dermis containing microencapsulated NGF-expressing NIH-3T3 cells and study the effect of the microencapsule to the bioengineered dermis and seed cells. NGF gene was transfected into NIH-3T3 cells and enclosed into alginate-poly-L-lysine alginate (APA) microencapsulation and cultivated in vitro. Content of NGF in microencapsules culturing supernatant was measured by enzyme linked immunosorbent assay (ELISA) method. These microencapsules were co-cultured with epidermic cells and fibroblast cells. Bioengineered dermis was constructed with NGF-expressing micorencapsules as seed cells using tissue engineering method. NIH-3T3 microencapsules, empty microencapsules, normal culture media were control groups. After one week culture, the characteristics of the dermis were described by MTT test, the content of hydroxyproline (HP), HE staining and ultrastructure photograph. We found the NGF-expressing microencapsulates can secret NGF steadly after cultured 8w in vitro, promot the proliferation of epidermic cells and secret collagen of fibroblast cells. These functions can maintaine in bioengineered dermis. So NGF-expressing NIH-3T3 microencapsulates can promote the quality of bioengineered dermis. PMID- 17333894 TI - [Development of rotating perfusion bioreactor system and application for bone tissue engineering]. AB - A rotating perfusion bioreactor system has recently been developed in our laboratory to produce 3D dynamic culture condition, and the critical-sized scaffolds with interconnected microchennels were fabricated. Gas exchange occurs by semipermeable membrane covered on each side of bioreactor and gas-permeable peristaltic pump tube. Rotation and perfusion of culture media through large scaffolds enhance well mixing and mass transport of oxygen and nutrients in the bioreactor. Osteoblastic cells attached to microchennels are exposed to a low fluid flow-induced shear stress level. This bioreactor system overcomes several defects exited in static culture condition, improves the culture environment, facilitates osteoblast proliferation, differntiation, significant matrix production and mineralization, and the controllability of culture process is enhanced. Large scaffolds/osteoblast constructs were cultured in the bioreactor system for 14 days. Osteoblastic cells attached to microchannels of scaffolds were observed under scanning electron microscope (SEM). The results indicated that cells grew extensively in the microchennels of large scaffolds. PMID- 17333895 TI - [Characteristics of MSCs adhesion to polypeptides modified surface polymer PLGA [ASP-PEG]]. AB - In this study we examined the in vitro characteristics of MSCs adhesion to polypeptides modified surface of polymer PLGA-[ASP-PEG]. We study the adhesion of marrow stromal cells in biomaterials at diferrent times using a micropipette aspiration technique. Comparison the adhesion of PLGA-[ASP-PEG] combinating GRGDSPC polypeptides versus PLGA-[ASP-PEG]. The adhesive conditions of MSCs on the materials were observed by scanning electron microscope. Four hours after MSCs inoculating in biomerials, the cell adhesion force of PLGA-[ASP-PEG] is 172.78 +/- 15. 23N and the force of PLGA-[ASP-PEG] combinating GRGDSPC polypeptides is 209.47 +/- 92.59N. There are no difference between two biomaterials. After 12 hours,the adhesion force of PLGA-[ASP-PEG] combinating GRGDSPC polypeptides is 576.23 +/- 165.74N, and the cell force of PLGA-[ASP-PEG] is 261.84 +/- 100.09 N. There are very significant difference between the two biomaterials. However, after 24 hours,the adhesion forces of the two biomaterials have no difference. The density of MSCs on PLGA-[ASP-PEG]-GRGDSPC surface was much higher than that of PLGA-[ASP-PEG]. Combination polypeptides in the surface of biomaterials can enhance the adhesion of MSCs. PMID- 17333896 TI - [Study of a novel dissoluble adhesive and its application in tissue engineering]. AB - In order to prepare three-dimensional scaffolds with "ideal pore-structure" for tissue engineering, a novel water dissoluble adhesive was developed, and the property of adhesive as well as influence of experimental condition on bonded porogen assembly was investigated. Experimental results showed that it was possible to fabricate large dimensional porogen assembly with homogenous and controllable bonding extent by this adhesive, and a large dimensional (45 mm in diameter, 55mm in thickness) biodegradable poly(D,L-lactic acid)(PDLLA) scaffold resulting from bonded porogen was formed. The scaffolds with high porosity as well as with controllable and homogeneous inner-structure can be easily formed. In addition, pore size of scaffolds as well as diameter of openings can be controlled by adjusting the porogen size and bonding degree in bonded porogen assembly. PMID- 17333897 TI - [In vivo degradation and tissue compatibility of poly-L-lactide/beta-tricalcium phosphate composite rods for internal fixation of bone fractures]. AB - Abstract Poly-l-lactide/beta-tricalcium phosphate (PLLA/betaTCP) composite was obtained by combining ground beta-TCP with PLLA, and absorbable rods were prepared by injection moulding. Degradations of the rods were investigated by scanning electron microscope (SEM), mass loss, molecular weight and bending strength changes. At the beginning of in vivo degradation of the rods, the molecular weight of PLLA decreases sharply with the less mass losses of the rods. As in vivo degradation progress, the surfaces of the rods changed roughly, while micropores and fine groove were observed in the inner part of the rods. The bending strength of composite rods decreased from 151 MPa to 106 MPa after in vivo degradation of 12 weeks. Tissue test reveal that PLLA/beta-TCP composite has good tissue compatibility compared with PLLA. PMID- 17333898 TI - [Preparation of biodegradable and sustained release gel of tinidazole]. AB - The objective of this study was to prepare a biodegradable poly (DL-lactide) injectable gel of tinidazole. The formulation parameters evaluated in this study included polymer molecular weight, polymer concentration, solvent and drug loading, and orthogonal design was used to optimize the formulation. The preferable formulation was that 30% (w/w) poly(DL-lactide) (MW is 5 700) dissolved in 70% (w/w) N-methyl-2-pyrrolidone with 4%-6% (w/w) tinidazole. PMID- 17333899 TI - [Preparation and in vitro characterization of novel hydrophilic poly(D,L lactide)/poly (ethylene glycol)-poly (lactide) composite scaffolds]. AB - A new technique was developed to fabricate PDLLA and PDLLA/PELA composite scaffolds by thermally induced phase separation in combination, with particulate leaching. Effects of PDLLA/PELA ratio, PEG/PLA ratio and PEG molecular weight on properties of mechanics, degradation behavior and cell toxicity as well as morphological properties were investigated. As the result showed, by thermally induced phase separation/ particulate-leaching, a unique morphology that macropores (100-250 microm) and micropores (5-40 microm)coexisted in the scaffold was obtained. An increase of PEG content or a decrease of PEG molecular weight raised the porosity of the scaffold. A decrease of PDLLA/PELA ratio or an increase of PEG/PLA ratio weakened mechanical properties and accelerated the degradation of the scaffold. PDLLA and PDLLA/PELA scaffolds didn't show cell toxicity. When PDLLA/PELA ratio was 3:1 and PEG5000/PLA ratio was 25:75, the scaffold got a regular, highly interconnected, macro-co-micro porous structure. PMID- 17333900 TI - [Alpha,beta-poly[(N-hydroxypropyl/aminoethyl)-DL-aspartamide -co-L-lysine]: potential non-viral vehicle for gene delivery]. AB - A series of Poly[aspartic acid-co-L-lysine](PAL) are copolycondensed by DL aspartice acid and L-lysine with different ratios. Their constructions are identified by the spectra of 1H-NMR, FT-IR, X-Ray). These spectra are proved to have good regularity of these copolymers. alpha,beta-Poly[(N hydroxypropyl/aminoethyl)-DL-Aspartamide-co-L-lysine] (PHAAL) is synthesized by ring-opening poly [aspartic acid-co-lysine] (PAL). PHAAL has good degradability in the phosphoric acid buffer solution (0.01 M, pH = 7.4) in the enzyme solution (Papain, Trypsine). PHAAL appeared tobe low cytotoxicity in Hela, ECV-304, Bcap37 cell lines, which was quantified by MTT assay. The combination ability of PHAAL with plasmid DNA was evaluated by agarose gel electrophoresis with agarose gel (1.0% w/v) containing ethidium bromide (0.25 microg/ml). The PHAAL with higher ratios of lysine in the copolymers have higher ability of condensing DNA. In summary, PHAAL, the polyaminoacid materials, could be one kind of macromolecule materials tobeused as the non-viral gene vehicle. PMID- 17333901 TI - [Particle image velocimetry in measuring the flow fields distribution in carotid artery bifurcation model]. AB - To understand the local hemodynamics of modified TF-AHCB carotid bifurcation model, using particle image velocimetry technique to measure the instantaneous velocity distribution of the model attatched to a circuit. The velocity was controlled by regulating the height of the reservoir. The working fluid consists of glycerine and water mixture with viscosity of 3.75 mPa.s similar to human blood. Instantaneous velocity fields were obtained by PIV and the shear stresses were calculated according to the velocity. The results showed that inside the model, there were a large flow separation and an anticlockwise rotating vortex on the lateral wall of ICA, The location and distance of the vortex changed with the flow velocity. The higher the flow velocity, the smaller the vortex distance, and the farther the location. The shear stresses on the lateral wall were significantly lower in all work condition. And there a low shear stress kernel when the velocity was lower than 0.839 m/s. The location of the low shear stress was just the position of atherosclerosis. The flow pattern inside the model consists of large flow separation and vortex zones. And there are low shear stress zones at the lateral wall of ICA, Where are thought to be associated with the genesis of atherosclerosis. PMID- 17333902 TI - [Three-dimensional motion analysis of right ventricular based on an electrophysiologic-mechanical composite heart model]. AB - Based on our previous electrical heart model, an electromechanical biventricular model was constructed by means of composite material theory and the finite element method. And the 3-D motion of the right ventricular wall was simulated based on this model. The orientation of cardiac fibers and myocardial contractility were taken into consideration during simulation modeling. The propagation of electrical excitation was simulated using an electrical heart model, and the resulting active forces was used to calculate the ventricular wall motion. Regional deformation and Lagrangian strain tensors were calculated during systole. Displacements, minimum principal strains were used to describe the motion of the right ventricle. The simulation results are in good accordance with results obtained from MR tagging images reported in literatures. In addition, the results also show that although the maximum displacement occurs in the base of the heart, however, the maximum contraction occurs in the apex of the heart. Such result is very difficult to be obtained by means of animal experiment or human experiment. This study suggests that such electrophysiologic-mechanical biventricular models have the important significance to be used to assess the mechanical functions of the two ventricles. PMID- 17333903 TI - [Three-dimensional finite element stress analysis of mandibular unilateral distal extension with extra-coronal precision attachment]. AB - From alveolar bone and the complete dentition CT images, a three-dimensionalysis of nonlinear finite element model of mandibular unilateral distal-extension with extracoronal precision attachment was established. The contact elements were used between the denture and alveolar bone. The result shows that, the stress in the second premolar and periodontal tissue decreased obviously as the second abutment was added. However, the stress difference was unapparent as the third abutment was added. Considering various facts, the attachment with two abutments was suggested to be used. With the decrease of the periodontal tissue, the stress in the periodontal tissue increased, however the stress in the tooth changed slightly. Thestress in the periodontal tissue decreased effectively when the third abutment was added, as the tooth root was absorbed by 50%. In this situation, the extracoronal precision attachment can also be used. PMID- 17333904 TI - [The bionic artificial joint capsule study (1)--mechanics simulation]. AB - In this paper, a three-dimensional finite element analysis (FEA) model was created for bionic artificial joint with joint capsule. Finite element method (FEM) was used to calculate and simulate mechanics distribution of the joint capsule under different thickness of the joint capsule, different loading, and different angular displacements. The results of the simulation show that the maximum stress is created in the joint area between artificial joint capsule. And the effect of the thickness of the artificial joint capsule on the stress magnitude and distribution is depend on motion model. On standing situation, the maximum stress decreases with the increase of the thickness of joint capsule. However, on walking situation, the maximum stress increases with the increase of the thickness of joint capsule. Whatever conditions simulated, the maximum stress of the artificial joint capsule is not over the limit of the material strength (9.97 megapascals). All the large stress, which gained from the simulation under different situations, locates at the interface between the capsule and the artificial joint. This is because the artificial joint and the capsule transfer loading each other at the interface. At the same time, supporting area of the capsule at the location of the interface is minimum for the whole vesicle. The stress concentration is inevitable at the interface due to the model structure. This result will offer guidance for the optimum joint structure of the capsule and the artificial joint. PMID- 17333905 TI - [Simulation on the process of female osteoporosis and its prevention by physical activity]. AB - Abstract The processs of female Osteoporosis and its prevention by Physical activity were simulated using anisotropic bone remodelling model with mechanostat combining with finite element method. The results show that bone mass declines slowly at the beginning, bone loss accelerates in postmenopause and bone mass declines 25. 84%-28.63% at the age of 60 and 38.50%-40.44% at the age of 80. Bone mass increases 3.05%-10.26% by an increase of 10%-20% in physical activity. The above results are consistent with clinical observations,which proves that declination of mechanical usage is the primary factor leading to osteoporosis, menopause quickens the process of female osteoporosis, physical activity can decelerate it. PMID- 17333906 TI - [An experimental research on the fabrication of the fused porcelain to CAD/CAM molar crown]. AB - This paper introduced the fabrication process of the fused porcelain to molar crown with CAD/CAM technology. Firstly, preparation teeth data was retrieved by the 3D-optical measuring system. Then, we have reconstructed the inner surface designed the outer surface shape with the computer aided design software. Finally, the mini high-speed NC milling machine was used to produce the fused porcelain to CAD/CAM molar crown. The result has proved that the fabrication process is reliable and efficient. The dental restoration quality is steady and precise. PMID- 17333907 TI - [The comparison of retention of diferent post and core systems]. AB - To study the effects of different post design on retention. 27 simulated tooth roots made of PMMA were divided into three groups, then manufactured the cement expanded composite screw post-core system (CECSP), cement screw post-core system (CSP) and cast metal post-core system (CMP). The root and post-core system was tensiled by the speed of 10 mm/min on the Instron 4302 and recorded the retention force. It appeared significantly different between retention force of CECSP and CSP and CAM (P < 0.05). As a result, the retention mechanical properties of CECSP was much better than those of cement screw post-core system and cast metal post core system. Therefore, it is possible to find a new way for restoration of endodontically treated teeth. PMID- 17333908 TI - [Changes of sarcolemma Na+/K+ ATPase and sarcoplasmic reticulum membrane Ca2+ ATPase activity after stem cell transplantation in chronic heart failure]. AB - To assess the changes of sarcolemma Na+/K+ ATPase (CMNKA) and sarcoplasmic reticulum membrane Ca2+ ATPase (SERCA) activities after stem cells transplantation in heart failure. Rabbit was used as heart failure model by intravenously injecting adriamycin. Autologous bone marrow mononuclear cells (BMCs), bone marrow mesenchymal stem cells (MSCs) or skeletal myoblasts (SMs) were introduced into coronary arteies through the root of aorta when two balloons occluding just above sinus of Valsalva. After 4 weeks, left ventricular ejection fraction (LVEF)was evaluated by echocardiography, and the activities of CMNKA and SERCA were measured by colorimeter. In BMCs (n=8)and MSCs (n=8) group, LVEF were significantly improved (P < 0.05). No significant improvement were seen in SMs group (n=6) compared to sham group (n=8). The CMNKA activity in all stem cells groups was significantly increased compared to sham group (P < 0.05). Meanwhile, in comparison with sham group, the incremental tendencies of SERCA activity were seen in stem cells groups. In conclusion, stem cells transplantation could increase the activities of CMNKA and SERCA in heart failure, a possible mechanism to improve heart function. PMID- 17333909 TI - [Theoretical evaluation of the use of KT/Vurea and Ccr as indexes of peritoneal dialysis adequacy]. AB - Urea clearance index (KT/Vurea) and creatinine clearance weekly (Ccr) are main indexes to evaluate dialysis adequacy. In order to discuss whether they are suitable to evaluate peritoneal dialysis adequacy, we applied trans-peritoneum transport kinetic model and explored the transport characteristics of fluid and various solutes. We found that: (1) There was no specific relationship among the removal of solutes with different molecular weights; (2) There was significant difference between urea removal and fluid and sodium removal. Our results suggest that urea and creatinine removal do not represent other solutes and fluid removal. KT/Vurea and Ccr may thus not suit to be used alone to evaluate peritoneal dialysis adequacy. PMID- 17333910 TI - [Construction and application of learning science related phenotype ontology]. AB - Based on MeSH-2004, we constructed a Learning Science related phenotype Ontology with active server page (ASP) and database technology. It provides a canonical, systemic and structural term system for the study of learning science and its phenotypes include terms of behavior,psychology and mental disorder. By using this Ontology, we can integrate isomerous data. It will increase the efficiency of information acquisition, management and search,and provide a platform for data sharing and data mining. PMID- 17333911 TI - [Construction of promoter-trap library screening in vivo-induced gene in Streptococcus pneumoniae]. AB - To identify in vivo-induced gene in Streptococcus pneumoniae (S. pn) through a novel in vivo expression technology (IVET), a large promoter-trap library using galU and lacZ as the reporters was constructed. Based on the suicide vector pEVP3, a new vector pEVP3-galU was constructed with promoterless galU gene as an in vivo reporter. Firstly, promoterless galU gene was directly cloned into pEVP3 fusing with promoterless lacZ gene (an in vitro reporter). Then the random pieces of S. pn chromosomal DNA (200-500 bp), obtained by partial Sau3AI restriction digestion, were subcloned into the Bgl II site of pEVP3-galU. Upon introduction of the ligated plasmid library into E. coli DH5alpha by transformation, about 70,000 recombinants were recovered. Considering insert DNA orientation and insert size, this represents 5 coverage of the 2.2 Mb S. pn genome; 90% of these clones had 250- to 500-bp inserts. Thus, the library retained maximal complexity. Transformation by this plasmid library yield 450,000 S. pn transformants. The library was used to infect animals in intraperitoneal model. Those strains survived in vivo while exhibiting a white colony phenotype on TSA agar containing X-gal would indicate that the DNA fragment upstream of the galU reporter contained an in vivo-induced promoter. The promoter-trap library is suitable for screening in vivo-induced gene of S. pn. PMID- 17333912 TI - [Effect of nano-selenium on the activities of glutathione peroxidase and type-I deiodinase in the liver of weanling pigs]. AB - To study the effects of nano elemental selenium (Nano-Se) or sodium selenite (Na2SeO3) on the activities of glutathione peroxidase (GSH-Px) and Type-I deiodinase in the liver. A total of 234 weanling pigs (Duroc x Landrace x Yorkshire) at an average initial body weight of 8.3 kg were allocated to 13 treatments. The thirteen dietary treatments were basal diet only (containing 0.04 mg/kg Se), basal diet + 0.1, 0.2, 0.3, 0.4, 0.5, 1.0 mg/kg Se as Na2SeO3 or Nano Se, respectively. The results were as follows: Supplementation with 1.0 mg/ kg Se as Na2SeO3 reduced (P < 0.05) growth performance and GSH-Px activities as compared with the addition of a concentration range of 0.20-0.40 mg/kg Se. When Nano-Se was added to the diet, the growth and GSH-Px activities remained steady at the peak value as at a concentration of 1.0 mg/kg Se; There were no difference in the activities of GSH-Px between the treatments of Nano-Se and Na2SeO3 when added concentration of Se was 0.10-0.40 mg/kg. The pigs had higher (P < 0.05) activities of GSH-Px at a concentration range of 0.50 and 1.0 mg/kg as Nano-Se than Na2SeO3; Supplentation with Se increased the activity of Type- I deiodinase in liver, however, the increased extent was affected by neither Se sources nor added concentration of Se. The results implicated that for the best concentration range of Weinberg curve, Nano-Se is wider than Na2SeO3. PMID- 17333913 TI - [Study on effects of bioelectric parameters of rats in electromagnetic radiation of HV transmission line]. AB - With the development of economy and coming of information era, the chance of exposure to electromagnetic fields with various frequencies has been increased for every human. The effects of electromagnetic radiattion on human being's health are versatile. To study the effects of bioelctronic parameters of rats in the electromagnetic radiations of HV transmission line, EEG, ECG and CMAP were measured in rats exposed to simulating high-voltage transmission line electromagnetic radiation for over one year. Brain tissues were studied by Fourier transform infrared spectroscopy. The results showed that no significant difference between exposed group and control group in EEG; however the FT infrared spectra of brain tissues were different; the ECG of the exposed animals was considerably altered. Significant slowing of heart rate was observed in those rates exposed to EMFs; the latent period of CMAP in exposed group were not different compared with those of control group however there was a significant difference in wave amplitude of CMAP between the exposed group and control group. All results indicated that there must be some effects on bioelectric parameters of rats exposed to electromagnetic radiation of high-voltage transmission line for a long time. PMID- 17333914 TI - [Detection of heterogeneous type II collagen transplantation mediated cytotoxic response in vitro]. AB - To detect the cellular immunity state of New Zealand white rabbit immunized by pig type II collagen. The New Zealand white rabbit was immunized by type II collagen for sixty days. The plasma was collected at a regular interval and the anti-type II collagen antibodies were examined. At the sixtieth day, the peripheral circular lymphocytes and the lymphocytes separated from spleen cells of rabbit and lymph nodes were collected and were stimulated by type II collagen in vivo again. The regulation of reactive cellular proliferation caused by the stimulation was detected. The experiment samples were divided into two groups. The first group was the positive control group by adding different concentrations of PHA and the non-specific immunity was assayed. The different concentrations of type II collagen were added to the second group and the specific immunity was assayed. The lymphocytes of normal rabbits showed proliferation by PHA stimulation but no proliferation by the first stimulation of type II collagen. Obvious proliferation due to the stimulation of both PHA and type II collagen in the immunized rabbit were observed. It shows that certain concentration of heterogeneous collagen may cause an increase of anti-type II collagen antibody in immunized rabbit and may cause a proliferation of lymphocytes in rabbit spleen and peripheral blood. The heterogeneous type II collagen causes cellular immunity in vivo. PMID- 17333915 TI - [Experimental study of two histological quantitative methods of hepatic fibrosis]. AB - To evaluate the value of two histological quantitative methods of hepatic fibrosis: semiquantative scoring system (SSS) and image analysis by computer. The prophylactic and therapeutic effect of Ganzhifu on hepatic fibrosis induced by CCl4 were studied on a total 73 of specimens from liver tissue of rats. All specimen were analyzed quantatively by two methods of SSS marks and image analysis respectively. Difference between groups was compared and hydroxyproline (Hyp) content of each liver tissue was examined. Correlation analysis was done between SSS marks, image analysis and Hyp content. Both prophylactic and therapeutic study showed the same information. Results of SSS marks, image analysis and Hyp content were coincidence. It suggest that both SSS marks and image analysis were interrelated well with Hyp content (P < 0.01). The result suggests that both SSS marks of hepatic fibrosis and image analysis by computer can be taken as reliable histological quantitative method of hepatic fibrosis. PMID- 17333916 TI - [Construction and expression of an anti-GD2,ScFv-IL-2 fusion protein gene]. AB - By combining interleukin2 (IL-2) with a tumor specific antibody, immunotherapy of tumors may become more effective in the future. Anti-GD2 single chain antibody directed to the extracellular domain of GD2 disialoganglioside can result in an antitumor response in some pateins with tumors expressing GD2. In this study, the fusion protein consisting of GD2 single chain antibody (ScFv) and IL-2(Ala125) was constructed. Anti-GD2 ScFv and IL-2 genes were obtained by PCR, then the ScFv IL-2 gene was constructed by over lap PCR. The gene was inserted into the pMD18-T easy vector. Genes from pMD18-T -vector were inserted into expression vector pSE380. Recombinant expression vector was identified by restriction enzyme cutting and then was transformed into BL21. SDS-PAGE and Western blot analysis confirmed that the transformed E. Coli BL21 could express ScFv-IL-2 fusion proteins and the molecular weight is 43 kDa. The fusion protein was purified by affinity chromatograph and Sephacryl S-200HR then was identified through ELISA. The results show that the fusion protein retains the activities of both antigen binding and IL-2. PMID- 17333917 TI - [Cloning of a phyA gene and its over expression in E. coli]. AB - This research amplified the phyA gene with the designed and synthesized primers specific for the phyA gene full-length coding sequence. The phyA gene was from Aspergillus niger F246 by the polymerase chain reaction(PCR), which is selected and identified in our laboratory. After sequncing the coding sequence, it was confirmed that the construction of cloning vector was succeeded. The phyA gene fragment was recovered from the pMD18T-phyA and ligated with prokaryotic expression vector pET30a+ to construct the recombinant expression plasmid pET30a+ -phyA. It was expressed with IPTG induction in E. coli for high efficiency. A new protein band with apparent molecular weight 50 kDa was detected in the lysate of the transformed cell by using SDS-PAGE. The amount of the soluble fusion protein was about 40% of large intestine bacillus soluble protein of transformed cells, estimated by absorbance scanning of SDS-PAGE and protein quantitation. It's phytase activity was eight times over the natural phyase. So this research provides the basis of the study on obtaining large and high active phytase and developmant of the new microbial ecologicalagent. PMID- 17333918 TI - [Experiment studies on viscoelastic properties of erythrocyte membrane in patients with pulmonale during acute exacerbation]. AB - The membrane viscoelasticity of erythrocyte taken from both normal subjects and patients with cor pulmonale during acute exacerbation was investigated using a micropipette aspiration technique. Experimental results were analysed with vogit viscoelaticity model based on pioneering theory of Chein et al. The results showed that the erythrocyte membrane elastic moduli ((6.970 +/- 1.050) x 10(-3) dyn/cm) and viscous coefficients ((0.936 +/- 0.242) x 10(-4) dyn x s/cm) of the cor pulmonale patients was significantly higher than those of the normal subjects ((5.203 +/- 1.051) X 10(-3) dyn/cm, (0.620 +/- 0.053) x 10(-4) dyn x s/cm). The membrane elastic moduli, viscous coefficients, rigidity of erythrocyte, and viscosity were all increased. It may be the important subcellular mechanism to cause the decrease of erythrocyte deformability and hyperviscosity of blood in these patients. PMID- 17333919 TI - [Quantitative research on effects of electroacupuncture on different parameters on analgesia in rats with adjuvant-induced arthritis]. AB - To research the effects of electroacupuncture on different quantitative parameters on analgesia in rats with adjuvant-induced arthritis. Rats of adjuvant induced arthritis were treated by electroacupuncture with different waveforms. Pain threshold and swelling degree of joint were observed. Electroacupuncture parameters being selected were measured by frequency spectrum analysis. After treatment, the pain thresholds in the electroacupuncture groups with different waveforms were higher than that of the model group (P < 0.05, P < 0.01); the local swelling degree of inflammation of the electroacupuncture groups were higher than that of the model group (P < 0.01), but was lower than that of the control group (P < 0.05, P < 0.01). Frequency, current, voltage and pulse width of successive wave and intermittent wave were similar. Frequency,current, voltage and pulse width of sound electric wave changed continuously. The results were that all the electroacupuncture with different waveforms had the analgesic effect in rats with adjuvant-induced arthritis and the therapeutic effect of the electroacupuncture of sound electric wave was the best. It is reasonable and important that electroacupuncture parameter should be quantified. PMID- 17333920 TI - [Transfection efficiency comparison of cationic liposome-DNA complexes and lipid protamine-DNA complexes in vitro]. AB - After the preparation of cationic liposomes composed of DDAB/DOPE, cationic liposome-DNA complexes and lipid-polycation-DNA (LPD) complexes were formulated, respectively. Gel retardation assay was employed to select appropriate ratios of cationic liposomes to DNA of the liposome-DNA complexes. The morphology of LPD and liposome-DNA complexes was observed by transmission electron microscopy. The diameter and surface charge of LPD and liposome-DNA complexes were measured by photon correlation spectroscopy (PCS). Their transfection efficiencies in Chang cells and HepG2 cells were evaluated by beta-gal assay kit. It was found that LPD and liposome-DNA complexes had a regular spherical surface. However, compared with liposome-DNA complexes, LPD had rather smaller particle size and much higher transfection efficiency in Chang cells and HepG2 cells in vitro. LPD could be prepared easily with small particle sizes and high transfection activities. LPD may be a good non-viral gene delivery vehicle for applications in gene delivery. PMID- 17333921 TI - [A new monitoring method of spacial balance during paraplegic FES-assisted walking]. AB - This paper suggested a new method of spacial risk-trend trace (SRTT) to assess and monitor the spacial balance condition during paraplegic walking assisted by functional electrical stimulation (FES), which main component was a measurement system of upper limb support based on a standard walker. With the support data, the spacial positions of moving center of gravity could be located through the upper body mechanical model and, combining with the definition of walker rolling index, transmitted into SRTT to describe the balance conditions at different axial space. The experimental and clinical results demonstrated the new SRTT method was reliable and real-time. Its potential clinical usefulness in evaluating and monitoring FES-assisted paraplegic walking ability may provide the foundation to enact the relevant national rehabilitation criterions for effective FES usage. PMID- 17333922 TI - [The sample entropy and its application in EEG based epilepsy detection]. AB - It is of great importance for the detection of epilepsy in clinical applications. Based on the limitations of the common used approximate entropy (ApEn) in the epilepsy detection, this paper analyzes epileptic EEG signals with the sample entropy (SampEn) approach, a new method for signal analysis with much higher precision than that of the ApEn. Data analysis results show that the values from both ApEn and SampEn decrease significantly when the epilepsy is burst. Furthermore, the SampEn is more sensitive to EEG changes caused by the epilepsy, about 15%-20% higher than the results of the ApEn. PMID- 17333923 TI - [TCM diagnosis and reasoning method based on grey relational analysis]. AB - In view of the problem of TCM diagnosis expert system, a new computerized TCM diagnosis system is constructed by simulating the process of expert diagnostic process. A disease filter method and grey relational analysis method are introduced to simulate and evaluate the process of TCM diagnosis. PMID- 17333924 TI - [Measuring volume and density of human organs and its significance in medicine and forensic medicine: brain and heart part]. AB - The exact scales of volume and density of human internal organs were measured synchronously with the intelligentized volum-densimeter, which was made. by ourself. These primary values of normal and diffuse pathologic changes can refer easily and used for the diagnosis in human autopsy of pathology and forensic pathology. It is expectated to be co-operated widely in that the basic values of volume and density will be obtained from all organs of the human body with the population of different races. But up to now, we are still lack these primary values in anthropology and medicine. PMID- 17333925 TI - [Real-time monitoring method for ECG signals based on Kalman filter technique]. AB - In this paper, a prediction and real-time monitoring method for changing in ECG signals is proposed based on Kalman filter technique. It is important that the change point such as jump and drift could be predicted and diagnosed from the measurement, so as to keep it safely. The Kalman filter technique can be used in estimating system states in real-time way. The sudden changes of the estimation errors of system status can be used as the predictor for the physiologic changes. This method is validated in practice according to the experimental results. PMID- 17333926 TI - [Study on testing methods of the elastic nature for equivalent material of human skin]. AB - To the specificity of equivalent material of human skin mechanical properties, the static-load pressing method for testing the elastic nature of the equivalent material of human skin is proposed, and the designs experimental set for the test is designed. The result show that the method is correct and feasible. PMID- 17333927 TI - [The action of decorin in anti-fibrosis and anti-cancer]. AB - Decorin (DCN) is a member of the small leucine-rich proteoglycan gene family. Many studies indicated that DCN inhibited fibrosis and scar-formation by neutralization of TGF-P and interfering the binding of TGF-beta with its receptor, which induced ectopic deposition of extracellular matrix. Additionally, DCN can prevent the proliferation and metastasis of tumor cells by activating EGFR/MAPK/p21 signal pathway and inhibiting the cell proliferation pathway mediated by EGF-EGFR. It is suggested that the recombinant DCN had potential pharmaceutical potency in treatment of chronic fibrosis and neoplasm for its critical biological activities and low immunogenicity. PMID- 17333928 TI - [The relationship between intracellular actin distribution and morphology and cell adherence]. AB - It is believed that there exists some relationship between the distribution and morphology of intracellular actin and cell adherence. Cells are likely to be deteched when the quantity of actin filament decreases. Actin filaments locate in the fringe of cancer cells and cells cultured in static state, so that these filaments can stretch out and form pseudopodia to adhere to the matrix. When these cells are stimulated their pseudopodia retract so that they can easily be detached from the matrix. When external forces are exerted on cells to adhere and deadhere from the matrix, the morphology and distribution of skeleton actin will change, so as the cells' morphology. The skeleton actins in cells are changed differently to adapt to different external forces which are imposed on the cells. It is obvious that the relationship between the mechanism of cell adhering to the matrix and the morphology & distribution of actins needs more attention. PMID- 17333929 TI - [Biological effects and their applications in medicine of pulsed electric fields]. AB - Pulsed electric fields can induce various kinds of biological effects that are essentially different from the normal electric fields, especially the interactions of Nanosecond Pulsed electric field (nsPEF) with cells. The biological effects of different pulsed electric fields on cell membranes, cytoplasmic matrixes, cell growth are introduced in this paper. Based on these effects, some applications of pulsed electric fields in cancer therapy, gene therapy, and delivery of drugs are reviewed in details. PMID- 17333930 TI - [Progress on reasech of drug-coated stent]. AB - Drug-coated stent play an important role in percutaneous transluminal coronary angioplasty (PTCA), and it constitutes an innovation to further reduce the incidence of restenosis. In this paper, the mechanisms and the process of endovascular stent implantation,and the principles of drug release of drug-coated stent are reviewed. Especially, polymer coated design and the further development of drug eluting stents are discussed. PMID- 17333931 TI - [The development of research on membrane oxgenator application]. AB - Extra-luminal flow hollow fiber membrane oxygenator (ELFHFMO) has been widely applied in cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) or extracorporeal life support (ECLS) because of its advantages over other types of MO. But its low hemocompatibility and durability are the major problems in clinical application that even have limited its wide application. In this paper, we reviewed the recent researches on how to improve the hemocompatibility and durability of ELFHFMO. PMID- 17333932 TI - [Review of driver fatigue/drowsiness detection methods]. AB - Driver fatigue/drowsiness is one of the important causes of serious traffic accidents and results in so many people deaths or injuries, but also substantial directly and indirectly economic expenses. Therefore, many countries make great effort on how to detect drowsiness during driving. In this paper, we introduce the recent developments of driver fatigue/drowsiness detection technology of world wide and try to classify the existing methods into several kinds according to different features measured, and analyzed. Finally, the challenges faced to fatigue/drowsiness detection technology and the development trend are presented. PMID- 17333933 TI - [T-DNA-induced mutations in transgenic plants]. AB - The review surveys experimental data on changes of individual traits in genetically modified (transgenic) plants. The attention is focused on mutations induced by T-DNA insertions upon Agrobacterium-induced transformation of dicotyledonous plants. The character of mutation appearance in transgenic plants is examined. The prospects of mutations induced by T-DNA insertions are considered. PMID- 17333934 TI - [Distorted heterochromatin replication in Drosophila melanogaster polytene chromosomes as a result of euchromatin-heterochromatin rearrangements]. AB - Studies of the position effect resulting from chromosome rearrangements in Drosophila melanogaster have shown that replication distortions in polytene chromosomes correlate with heritable gene silencing in mitotic cells. Earlier studies mostly focused on the effects of euchromatin--heterochromatin rearrangements on replication and silencing of euchromatic regions adjacent to the heterochromatin breakpoint. This review is based on published original data and considers the effect of rearrangements on heterochromatin: heterochromatin blocks that are normally underrepresented or underreplicated in polytene chromosomes are restored. Euchromatin proved to affect heterochromatin, preventing its underreplication. The effect is opposite to the known inactivation effect, which extends from heterochromatin to euchromatin. The trans-action of heterochromatin blocks on replication of heterochromatin placed within euchromatin is discussed. Distortions of heterochromatin replication in polytene chromosomes are considered to be an important characteristic associated with the functional role of the corresponding genome regions. PMID- 17333935 TI - [Revealing of allelic polymorphism in the populations of parthenogenetic lizards Darevskia dahli (Lacertidae) using locus-specific PCR]. AB - Locus-specific PCR was used to study the genetic polymorphism in three populations of parthenogenetic lizard species Darevskia dahli. The analysis was carried at the two (GATA)n-containing loci (Du215 and Du281) using the sample of 26 individuals. A total of eight Du215 and three Du281 allelic variants were detected. It was demonstrated that all the lizards examined were heterozygous at these loci. In 12 animals, unusual Du215 allelic variant was revealed, the origin of which was thought to be associated with different types of genomic rearrangements, or segmental duplication. The populations studied were substantially different relative to the levels of allelic polymorphism, which could be explained by different habitation conditions, leading to accumulation of mutations in noncoding genome regions. PMID- 17333936 TI - [Role of general transcription factors and the TFTC complex in transcription activation in vivo as revealed with a model of the hsp70 gene]. AB - General transcription factors (GTFs) were tested for the presence on the promoter of the Drosophila melanogaster hsp70 gene in vivo. TBP, TBP-associated TAF proteins, TFIIB, TFIIF (RAP30), TFIIH (XPB), the TFTC complex (GCN5 and TRRAP), and a Mediator complex subunit (MEDI 3) were detected on the promoter before heat induction. Heat exposure significantly reduced the contents of TBP, TAF proteins, TFIIB, and TFIIF (RAP30), while these proteins were detected in ecdysone inducible loci. It was assumed on the basis of these findings that a special mechanism induces transcription from the hsp70 promoter and that the apparent presence or absence of GTFs does not always reflect the transcriptional status of a gene. PMID- 17333937 TI - [Conservation of the MC domains in eukaryotic termination factor eRF3]. AB - Eukaryotic translation termination employs two protein factors, eRF1 and eRF3. Proteins of the eRF3 family each consist of three domains. The N and M domains vary in different species, while the C domains are highly homologous. The MC domains of Homo sapiens eRF3a (hGSPT I), Xenopus laevis eRF3 (XSup35), and Mus musculus eRF3a (mGSPTI) and eRF3b (mGSPT2) were found to compensate for the sup35 21(ts) temperature-sensitive mutation and lethal disruption of the SUP35 gene in yeast Saccharomyces cerevisiae. At the same time, strains containing the MC domains of the eRF3 proteins from different species differed in growth rate and the efficiency of translation termination. PMID- 17333939 TI - [Highly sensitive systems for experimental insertional mutagenesis in repair deficient genetic environment in Drosophila melanogaster: new opportunities for studying postreplication repair of double-stranded DNA breaks and mechanisms of transposable element migration]. AB - Spontaneous mutations in Drosophila melanogaster are related mainly to transposable elements (TEs). They are caused by both migration of TEs over the genome (transpositions) and the ability of TEs to induce chromosomal mutations. Migration of DNA transposons is accompanied by formation of double-strand DNA breaks (DSBs), which are repaired by host repair systems encoded by genes for recombination repair. We relied on this notion to develop a combined approach to the investigation of the type of DNA breaks accompanying transpositions; investigation of systems involved in DSB repair; and detection of repair genes, whose products were involved in repair of DNA breaks induced by TE transposition. The approach is based on the combination of experimental insertional mutagenesis systems and genetic environment deficient for enzymes of the repair system in a single genome. The main advantages of this approach are versatility, wide applicability, and simple design. PMID- 17333938 TI - [Initiator protein DnaA of Escherichia coli is a negative replication regulator of the linear phage-plasmid N15]. AB - Temperate bacteriophage N 15 in the lysogenic state is incapable of integrating in the chromosome of Escherichia coli and represents a linear plasmid with covalently closed ends. The phage repA gene, the product of which possesses activities of primase and helicase, ensures replication of N15 DNA. The ori site of initiation of N15 replication contains binding sites for RepA and a potential site of binding the bacterial initiator protein DnaA. It was shown in our work that replication of miniplasmids based on N15 replicon as well as replication of N15 DNA during lytic growth do not depend on DnaA. Moreover, introducing mutations into the potential DnaA binding site increases the copy number of circular and linear miniplasmids that contain repA gene. These data suggest that DnaA is a negative rather than positive regulator of phage N15 replication. This is assumed to be caused by properties of interaction between RepA and DnaA during initiation of N15 replication or by transcriptional silencing of repA gene due to the binding of DnaA to the ori site located within the coding repA sequence. PMID- 17333940 TI - [Polymorphism and differentiation of multilocus DNA markers in natural populations of Drosophila melanogaster]. AB - Using multilocus (RAPD) markers, variation and divergence of genomic DNA was examined in two Drosophila melanogaster populations from Russia and three populations from Ukraine. The populations were found to exhibit high polymorphism at RAPD markers. Estimation of genetic distances between the populations showed low differentiation of geographically distant populations of D. melanogaster. Significant gene flow between the D. melanogaster populations was found, which depended on the geographical distance between them. PMID- 17333941 TI - [Characteristics of the structural organization of the DIP1 gene in Drosophila melanogaster strains mutant for the flamenco gene]. AB - Molecular cloning of the DIP1 gene located in the 20A4-5 region has been performed from the following strains with the flamenco phenotype: flamSS (SS) and flamMS (MS) characterized by a high transposition rate of retrotransposon gypsy (mdg4), flampy + (P) carrying the insertion of a construction based on the P element into the region of the flamenco gene, and flamenco+. The results of restriction analysis and sequencing cloned DNA fragments has shown that strains flamSS, flamMS, flampy +(P), and flamenco+ considerably differ from one another in the structure of DIP1. Strains flamss and flamMS have no Dral restriction site at position 1765 in the coding region of the gene, specifically, in the domain determining the signal of the nuclear localization of the DIP1 protein. This mutation has been found to consist in a nucleotide substitution in the recognition site of DraI restriction endonuclease, which is transformed from TTTAAA into TTTAAG and, hence, is not recognized by the enzyme. This substitution changes codon AAA into AAG and is translationally insignificant, because both triplets encode the same amino acid, lysine. The Dral gene of strainsflamSS andflamMS has been found to contain a 182-bp insertion denoted IdSS (insertion in DIP1 strain SS); it is located in the second intron of the gene. The IdSS sequence is part of the open reading frame encoding the putative transposase of the mobile genetic element HB1 belonging to the Tcl/mariner family. This insertion is presumed to disturb the conformations of DNA and the chromosome, in particular, by forming loops, which alters the expression of DIPI and, probably, neighboring genes. In strains flamenco+ and flampy + (P), the IdSS insertion within the HB1 sequence is deleted. The deletion encompasses five C-terminal amino acid residues of the conserved domain and the entire C-terminal region of the putative HB1 transposase. The obtained data suggest that DIP1 is involved in the control of gypsy transpositions either directly or through interaction with other elements of the genome. PMID- 17333942 TI - [Efficiency of the prediction of carcinogenic activities of chemical substances based on scoring somatic mutations in the soybean Glycine max (L.) Merrill]. AB - The efficiency of scoring somatic mutations in soybean (Glycine max (L.) Merrill) leaves as a test for carcinogenic activity of chemical substances in rodents has been evaluated. The efficiency of the test used alone or as part of a battery of tests has been estimated. The mutagenic activities of some chemical substances estimated using the soybean test are presented. Selective information on the carcinogenic activities of substances obtained in special carcinogenicity tests has been used as a quantitative measure of the efficiency of the tests with soybean leaves. To estimate the weight of evidence for the presence of this activity in the tested substances, a special function has been used whose values are uniquely related to the complete information, which is the sum of a priori information and the information obtained after testing. In general, the results have shown that the somatic mutation score test using soybean leaves is at least as efficient as the well-known tests that are generally used now, such as the Ames test and the chromosome aberration score test using mammalian cells in vitro. This test may be promising for the formation of efficient short-term test batteries. PMID- 17333943 TI - [Allelic polymorphism of kappa-casein gene (CSN3) in Russian cattle breeds and its informative value as a genetic marker]. AB - The frequencies of the kappa-casein gene (CSN3) alleles and genotypes have been determined in five Russian cattle breeds (Bestuzhev, Kalmyk, Russian Black Pied, Yaroslavl, and Yakut breeds) by means of PCR-RFLP analysis using two independent restriction nucleases (HinfI and TaqI) and by allele-specific PCR. Typing alleles A and B of CSN3 is of practical importance, because allele B is correlated with commercially valuable parameters of milk productivity (protein content and milk yield) and improves the cheese yielding capacity. The frequencies of the B allele of CSN3 in the breeds studied vary from 0.16 to 0.50; and those of the AB and BB genotypes, from 0.27 to 0.60 and from 0.02 to 0.23, respectively. The Yaroslavl breed had the highest frequencies of CSN3 allele B and genotype BB (0.50 and 0.23, respectively). The frequencies of the B allele and BB genotype in other breeds studied varied from 0.25 to 0.32 and from 0.03 to 0.09, respectively. In none of the breeds studied have the observed and expected heterozygosities been found to differ from each other significantly. However, the observed genotype distributions significantly differ from the expected one in some herds (in most such cases, an excess of heterozygotes is observed). Two herds of the Yaroslavl breed dramatically differ from each other in the heterozygosity level: a deficit (D = -0.14) and an excess (D = 0.20) of heterozygotes have been observed at the Mikhailovskoe and Gorshikha farms, respectively. In general, however, the heterozygosity of the Yaroslavl breed corresponds to the expected level (D = 0.04). Analysis of breeds for homogeneity with the use of Kulback's test has shown that all cattle breeds studied are heterogeneous, the CSN3 diversity within breeds being higher than that among different breeds, which is confirmed by low Fst values (0.0025-0.0431). Thus, a DNA marker based on CSN3 gene polymorphism is extremely important for breeding practice as a marker of milk quality; however, it is inapplicable to marking differences between breeds or phylogenetic relationships between cattle breeds because of the high diversity with respect to this locus within breeds. PMID- 17333944 TI - [A method for transformation of Drosophila germline cells with a high concentration exogenous DNA]. AB - A method for transformation of Drosophila germline cells without DNA capillary injections is proposed. The method involves a microneedle puncture of embryos and can be realized using simple equipment. PMID- 17333945 TI - [Repair of cisplatin-DNA adducts in mutants for genes controlling spontaneous and induced mutagenesis in Saccharomyces cerevisiae]. AB - Sensitivity to the lethal action of the anticancer substance cisplatin was studied in the yeast mutants himl, hsm2, hsm3, and hsm6, deficient for repair of spontaneous and induced mutations. The himl and hsm3 mutants were as resistant to the agent under study as the wild-type strain. The survival of the double mutant rad2 hsm3 was higher than that of the single mutant rad2. The hsm2 and hsm6 mutants were more cisplatin-sensitive than the wild type. Cisplatin was shown to have high mutagenic and recombinogenic effects on yeast cells. PMID- 17333946 TI - [A RAPD fingerprinting of sibling species of the Drosophila virilis group]. AB - A comparative analysis of the sibling species of Drosophila virilis was performed by RAPD-PCR technique using a set of random primers. The degree of relatedness was studied by cluster analysis (UPGMA) and multi-dimensional scaling. The resulting pattern of species relationships contradicts the classical taxonomy. The main result of the cluster analysis is that D. virilis does not cluster with the remaining three species of its phylad, while according to multidimensional scaling, D. virilis is equidistant from all the species of its group, from both the species of its phylad and the species of the montana phylad. The montana phylad is extremely heterogeneous; moreover, the species D. littoralis, D. ezoana, and D. kanekoi appear to be closer to the virilis phylad than to the other species of the montana phylad, wherein these species are traditionally included. The phylogenetic relationships between the studied species discovered using RAPD fingerprinting comply with the results obtained using protein markers and quantitative traits. PMID- 17333947 TI - Pattern of care for schizophrenia patients in Granada (Spain): a case register study. AB - AIMS: This study sets out to explore the use flow of mental health services by a cohort of patients with schizophrenia located in Granada (Spain). METHODS: All cases (N = 844) included in the analysis were users of the community mental healthcare public service provided in the area. The Markov chain model was used to calculate the probability of transition from one type of contact with mental health services resources to another type of contact in the next month, over a three-year follow-up. RESULTS: For a given one-month period, for each level of service contact, most patients continued to use the same level of care. CONCLUSIONS: Our results can be interpreted as a reflection of adequate continuity of mental health care provided by the Andalusian community service. PMID- 17333948 TI - Case management for individuals with a severe mental illness: a 6-year follow-up study. AB - BACKGROUND: As a part of a set of reforms launched in 1995, 10 pilot case management services were established in Sweden, which have been subject to an evaluation with regard to outcome and changes in use of services. The present study was designed to provide information about client outcomes over a 6-year follow-up period. AIMS: The aim of the study was to investigate changes during the follow-up period with regard to symptoms, needs for care, psychosocial functioning, quality of life and social network. METHODS: The study used a time series design with 6-year follow-up of client outcomes. RESULTS: Of the original 176 clients, 92 clients participated in the 6-year follow-up. Improvements were found in a number of clinical aspects, quality of life and social network, and a decrease in use of psychiatric services during the follow-up period. CONCLUSIONS: The findings support results from earlier studies showing a decrease in use of psychiatric services and sustained improvements in social functioning. The study also supports the findings that client outcomes change over time and that certain outcomes do not appear in a short-term perspective. PMID- 17333949 TI - A qualitative study of patients' perceptions of a 'minimal' psychological therapy. AB - BACKGROUND: Access to psychological therapy is often difficult. Problems with access may be overcome through 'minimal interventions' (such as books and computer programs), which encourage self-help for mental health problems and are less dependent on the availability of specialist therapists. However, to be effective, such interventions must be acceptable to patients. AIMS: To use qualitative methods to explore patient attitudes, by examining patient expectancies of psychological therapy and their experiences with a 'minimal intervention' (guided self-help). METHODS: Qualitative interviews (N = 24) were conducted with patients after they had received guided self-help for depression as part of a randomised controlled trial. RESULTS: There were important gaps between patients' expectancies of psychological therapy and their experience of the guided self-help. These gaps related to the process of therapy (e.g. time, professional expertise) and outcomes. Particularly salient was a theme relating to explanatory models. Patients were often seeking insight into the 'cause' of their current difficulties, whereas the minimal intervention was largely focused on symptom resolution. CONCLUSIONS: The effective implementation of 'minimal interventions' requires an understanding of the expectancies of patients concerning psychological therapy, in order to provide a basis for effective communication and negotiation between professionals and patients. PMID- 17333950 TI - Relationships between social functioning and quality of life in a population of Dutch adult psychiatric outpatients. AB - BACKGROUND: The relationship between social functioning and QOL in psychiatric patients has not been explicitly investigated before. AIMS: To investigate the relationship between social functioning and QOL in a population of psychiatric outpatients (N = 410) with a broad spectrum of psychiatric disorders. METHOD: Social functioning was assessed with the Groningen Social Behavior Questionnaire 100 (GSBQ-100) and the Global Assessment of Functioning (GAF) scale. QOL was measured with the WHO Quality of Life Assessment Instrument (WHOQOL-100). RESULTS: The study population experienced a wide range of problems concerning all aspects of social functioning. The numbers of problems were significantly higher compared with healthy controls and (partly) also compared with a norm group of psychiatric outpatients. Almost all scales of the GSBQ-100 were negatively correlated with all QOL aspects, whereas the GAF score correlated positively with all QOL aspects. In general, participants with problems on aspects of social functioning had lower QOL scores than those without such problems, even after a correction for the presence of psychopathology according to DSM-IV classification. CONCLUSION: In addition to the presence of psychopathology, social functioning is significantly related to QOL. Therefore, it should be considered more systematically in psychiatric assessment, treatment and program evaluation. PMID- 17333951 TI - A clients' perspective on demand-oriented and demand-driven health care. AB - BACKGROUND: In many Western European countries, there is an increasing request for demand-oriented and demand-driven approaches in health care. In these approaches, the emphasis is on the clients' perspective on healthcare policy and healthcare services. A study was conducted to gain insight into the clients' view of health care. METHODS: In 2004 a survey was conducted in the Netherlands among 4250 ambulatory mental health clients, by means of a postal questionnaire. To include clients with different experiences of mental health care, the sample was stratified according to the length of the treatment history. A total of 865 clients responded to the survey. RESULTS: Elements that are found to be important to most clients are that 'needs are determined in consultation with the client', that 'the client is treated in a pleasant manner' and that 'the professional informs the client about the possibilities in his/her situation'. Significant differences were found between groups with different background factors: income, education, age, sex and treatment history all had significant correlations. CONCLUSION: Most clients in ambulatory mental health care appreciate the demand oriented and demand-driven approaches. However, not all the elements are appreciated in the same manner. In general, clients do not seem to care much about who makes the decisions, but they care much more about the way the decision making process is carried out. Clients especially value being heard and being involved in the process as a serious party. PMID- 17333952 TI - The mental health expert patient: findings from a pilot study of a generic chronic condition self-management programme for people with mental illness. AB - BACKGROUND: Less than optimal outcomes and escalating costs for chronic conditions including mental illness have prompted calls for innovative approaches to chronic illness management. AIMS: This study aimed to test the feasibility and utility of combining a generic, clinician administered and peer-led self management group approach for people with serious mental illness. METHOD: General practitioners and mental health case managers used a patient-centred care model (the Flinders model) to assist 38 patients with serious mental illness to identify their self-management needs, and match these with interventions including Stanford peer-led, self-management groups and one-to-one peer support. Self-management and quality of life outcomes were measured and qualitative evaluation elicited feedback from all participants. RESULTS: Collaborative care planning, combined with a problems and goals focused approach, resulted in improved self-management and mental functioning at 3 to 6 months follow-up. The Stanford self-management course was applicable and acceptable to patients with serious mental illnesses. Qualitative feedback was highly supportive of this approach. CONCLUSIONS: Generic, structured assessment and care planning approaches, resulting in self-management education targeted to the individual, improved self-management and quality of life. Patients and service providers reported considerable gains despite the challenges associated with introducing a generic model within the mental health and general practice sector. PMID- 17333953 TI - Adverse incidents, patient flow and nursing workforce variables on acute psychiatric wards: the Tompkins Acute Ward Study. AB - BACKGROUND: Adverse incidents (violence, self-harm and absconding) can cause significant harm to patients and staff, are difficult to predict, and are driving an increase in security measures and defensive practice. AIMS: To explore the relationship between adverse incidents on acute psychiatric wards, admissions and nursing workforce variables. METHODS: A retrospective analysis of officially collected data covering a period of 30 months on 14 acute wards at three hospitals. This data included 69 serious untoward incidents. RESULTS: Adverse incidents were more likely during and after weeks of high numbers of male admissions, during weeks when other incidents also occurred, and during weeks of high regular staff absence through leave and vacancy. CONCLUSIONS: It may be possible to predict adverse incidents. Careful staff management and deployment may reduce the risks. PMID- 17333954 TI - Nonlinear relationship between length of residence and depression in a community based sample of Vietnamese Americans. AB - BACKGROUND: Length of residence has been viewed as an indicator of acculturation among immigrants and refugees in their host society. This study aims to test an inverted U relationship between length of residence and depression in a community based sample of Vietnamese Americans. METHODS: Data were collected from a community-based survey of adult Vietnamese Americans living in an East Coast metropolitan area consisting of 349 respondents aged 18 and older. However, due to missing data, the actual sample in our regression analysis using listwise deletion method is 311. Among the participants, 52.1% are female (n = 182), and 47.9% are male (n = 167). The age of the respondents ranges from 18 to 73 years with the average age being 38.76 (SD = 13.76). The average number of years that the participants lived within the United States was 7.01 years (SD = 5.22). RESULTS: Findings from a polynomial regression analysis support the hypothesis that depression levels tend to be high during the first decade of initial resettlement. However, after approximately 12.5 years, depression levels decrease. CONCLUSION: As revealed by the data and community experts, immigrants/ refugees tend to suffer from higher levels of psychological problems during their first decade of resettlement. It takes more than a decade for a non-English speaking immigrant or refugee to adjust psychologically into his/her host society. PMID- 17333955 TI - Working together. PMID- 17333956 TI - Oral bisphosphonates and osteonecrosis of the jaw. PMID- 17333957 TI - Restorative disappointments. PMID- 17333958 TI - Light it up: headlights are the answer. PMID- 17333959 TI - Microleakage of three conventional glass ionomers using 45Ca and methylene blue. AB - This study sought to compare the sealing ability of two conventional ionomers and a new intermediate/provisional ionomer formulation using sequential applications of two different tracer methodologies. Thirty freshly extracted (< 6 months) human third molars, stored in 0.1% sodium azide solution, were divided randomly into three experimental groups for preparation of simulated Class V caries at the cementoenamel junction of the facial surfaces. Three materials were used to restore the cavity preparations. After restoration, the teeth were thermocycled for 100 cycles (between 4.0 degrees C and 58 degrees C). To evaluate the microleakage of the materials and compare the tracer's ability to measure microleakage, the teeth were subjected to 45Ca and methylene blue. Treated teeth were bisected longitudinally through the restoration, then each sectioned tooth half was scored by three independent evaluators using a 0 to 4 scale, depending on the tracer penetration. The results showed that all of the materials investigated performed well and no statistical differences were found among the materials, the tracer used, or the margin evaluated. PMID- 17333960 TI - Root perforations following endodontics: a case for surgical management. AB - Despite technological advancements in dental instrumentation and techniques, endodontic mishaps remain commonplace. Perforations during access preparation, canal instrumentation, root filling, or preparation of post space are not unusual and instruments may fracture during filing or reaming or when attempting to bypass fractured instruments in the root canal. Many of these complications are hard to avoid due to extreme variations in root canal anatomy, root shapes, curvatures, and canal calcification. Procedural errors impede proper endodontic therapy and increase the risk of treatment failure; as a result, the prognosis is compromised, especially in nonvital teeth or teeth with periradicular lesions. Perforations may lead to short-term or long-term complications (that is, infection, periapical cyst, or granuloma formation); in addition, restorative material may be extruded through the perforation. Clinicians often have difficulty diagnosing and treating root perforations, particularly in posterior teeth (specifically in the area of the mandibular bifurcation); however, such complications do not mean that the tooth must be extracted. This article discusses treatment of perforations near the bifurcation of a mandibular first molar and an apical perforation in a premolar. Both teeth were salvaged via surgery without the use of additional biomaterials. PMID- 17333961 TI - Retrofitting technique for a crown or abutment following coronal fracture. AB - The fracture of tooth structure and/or restorative material within a crown or fixed partial denture abutment poses a restorative challenge. Depending upon the severity of the fracture and health of the tooth or teeth involved, the restoration often can be re-cemented, restoring the tooth to a serviceable condition. This article describes a technique that provides a safe and efficient means of restoring the fractured tooth, thereby overcoming a major obstacle to the conventional recementation process. An application of the technique also is described. PMID- 17333962 TI - Microleakage study of different adhesive systems in Class V cavities prepared by Er,Cr:YSGG laser and bur preparation. AB - This study sought to compare the microleakage of composite resin restorations using two different dentin adhesive systems and two different modes of cavity preparation: a high-speed handpiece and an Er,Cr:YSGG laser. Twenty-five caries free permanent human premolars were assigned randomly into five groups of five. A high-speed handpiece was used to prepare Class V cavities on the buccal and lingual surfaces of 10 randomly selected teeth. Class V cavities were cut on the buccal and lingual surfaces of the remaining 15 teeth using the Er,Cr:YSGG laser system. Fifty cavities were prepared with enamel and dentin margins 1.0 mm below the cemento-enamel junction and assigned into five groups: I, II, and III by the Er,Cr:YSGG laser and IV and V by the high-speed handpiece. In all groups, the differences between gingival and occlusal leakage scores were statistically significant (p < 0.05). The occlusal and gingival scores of groups I and IV demonstrated statistically significant differences (p < 0.05). The lased group with additional acid etching revealed less microleakage than groups III and IV (p < 0.05). Both self-etch and total-etch adhesive systems demonstrated acceptable microleakage scores when used on Er,Cr:YSGG laser-prepared cavities; however, additional acid etching after Er,Cr:YSGG laser preparation is recommended. PMID- 17333963 TI - Bacterial contamination of clinical examination gloves. AB - Dental clinicians have been wearing examination gloves routinely during clinical procedures since 1986, when the CDC advised using them as part of standard personal protective equipment recommendations. Initially, latex was virtually the only material available for examination glove construction; however, in recent years, numerous other materials have been utilized for glove construction in response to the increased recognition of latex allergies among patients and dental health care workers. Examination gloves are marketed as "non-sterile" according to the FDA, which sets specific standards governing the manufacturing and distribution of these products. This study examined the prevalence of bacterial organisms present in a variety of freshly opened glove boxes. The same glove boxes were put into clinical use for a period of time and re-tested for the presence of bacteria. The quantity of bacteria present on gloves in the new boxes differed in comparison to the gloves that remained in the used boxes. PMID- 17333964 TI - The leakage resistance of endodontic fiber obturators. AB - Fiber obturators have been introduced into endodontics but few reports exist regarding their efficacy compared to standard obturation materials. This study evaluated the leakage resistance of fiber obturators compared with other obturation materials. All specimens showed a progressive increase in leakage with time. The data indicate that fiber obturation and a new cone/sealer system provide the best canal obturation as evidenced by the leakage behavior. PMID- 17333965 TI - Solitary plasmacytoma of the maxilla--a case report and review of the literature. AB - Plasma cell neoplasms have been classified as multiple myeloma, solitary plasmacytoma, and extramedullary plasmacytoma. The solitary plasmacytoma of the maxilla is a rare condition that focuses solely on myelomatous tissue and is not disseminated to other parts of the skeleton. Some lesions appear to be benign and do not recur after complete removal, while others are locally invasive. The dense plasma cell infiltration that commonly is associated with inflammatory lesions within the oral tissues makes diagnosing plasmacytoma at this site problematic. This article presents a case of solitary plasmacytoma in the maxilla. Radiographic examination revealed an osteolytic lesion over the right maxillary bone, invading the maxillary sinus. A CT scan showed that the tumor mass occupied the right maxillary sinus and the lateral wall of the nasal cavity. The tumor cells were composed of densely packed, round, polygonal cell structures that were scattered in relatively sparse stoma. The neoplastic cells had a large, single eccentric nucleus, resembling typical plasma cells. The clinical, histopathological, and radiological features of solitary plasmacytoma are discussed. PMID- 17333966 TI - An implant versus a conventional fixed prosthesis: a case report. AB - The success of endosseous implant dentistry is widely acknowledged. Clinical research and subsequent innovations with both surgical and restorative techniques -as well as improved surface features and restorative components--have made endosseous dental implants a routinely accepted dental treatment modality. Patients and referring clinicians often specifically request dental implant therapy. This article presents an example of such a patient; however, in this case, a surgical ridge augmentation and fabrication of a conventional fixed prosthesis was selected as the treatment modality. The authors believe that all therapeutic modalities should be considered when adapting appropriate treatment plans for individual patients. PMID- 17333967 TI - Oral involvement in chronic graft versus host disease: a prospective study of 19 Brazilian patients. AB - Chronic graft versus host disease (cGVHD) is the most common late complication of allogeneic bone marrow transplantation. The oral cavity is the most common site of cGVHD involvement. This study sought to investigate the incidence of oral cGVHD, as well as the disease's impact on a patient's quality of life and the kind of lesions that resulted. Nineteen patients with cGVHD received a medical and dental evaluation; 18 (94.7%) had oral lesions. Nine patients (47.3%) demonstrated xerostomia and 6 (35.2%) demonstrated dysphagia. Six patients (35.2%) had a lichenoid clinical form of cGVHD in the oral cavity, 6 (35.2%) had an atrophic-ulcerative clinical form, 3 (17.6%) had a hyperceratotic clinical form, and 2 (10.5%) had mixed forms. The results demonstrated predominance of lichenoid and ulcerative-atrophic forms with similar incidence of these lesions. No factor that could contribute to the severity of cGVHD oral lesions was found. PMID- 17333968 TI - Temporal arteritis: don't let this disease fool you. AB - Temporal arteritis is a disease of older individuals that manifests with variable signs, symptoms, and pain in the head and jaw. This disease should be considered in the differential diagnosis if the dentist encounters a patient with puzzling complaints that are not explained by oral and physical findings. PMID- 17333969 TI - Use of conebeam computed tomography in dentistry. AB - Conebeam computed tomography (CBCT) is a technology new to dentistry that provides 3-D imaging of the oral and maxillofacial complex. Bitewing, periapical, and panoramic images are commonplace for diagnosis and treatment planning in dentistry. The 3-D data provided by conebeam technology uses a low quantity of radiation and provides insight into anatomy as an adjunct to 2-D imaging. As 3-D imaging becomes more prevalent, better diagnosis, treatment planning, and surgical experience can be achieved to improve patient care. PMID- 17333970 TI - Non-nutritive sucking with a pacifier: pros and cons. AB - The detrimental effects of prolonged pacifier use on the developing oral structures are often the primary focus of dental professionals; however, non nutritive sucking with a pacifier has other consequences that include not only harmful effect but positive influences as well. This article will address some of the issues for consideration regarding the use of pacifiers and provide information for appropriate recommendations to parents of infants and toddlers regarding the use and cessation of non-nutritive sucking with a pacifier. PMID- 17333972 TI - Slowly enlarging recurrent mass. Monostotic fibrous dysplasia. PMID- 17333971 TI - Effect of acetylsalicylic acid on aggregation of human platelets by Porphyromonas gingivalis. AB - This study investigated the effect of in vivo low-dose acetylsalicylic acid (ASA, aspirin) on human platelet aggregation induced in vitro by Porphyromonas gingivalis cells. Blood was collected from volunteers (n = 20), half of whom ingested 81 mg of aspirin 24 hours before donating blood. Low-dose aspirin inhibited P. gingivalis cell-induced platelet aggregation and produced an inverse correlation of inhibition to number of cells. At the higher concentration of cells used in this in vitro assay, aspirin inhibition was significant (P = 0.001); however, partial platelet activation was observed. The significance of partial platelet activation is discussed in this article, as is the relevance of platelet aggregation to the putative link between inflammatory periodontal disease and cardiovascular disease. PMID- 17333973 TI - Tender, swollen mandible. Abscess associated with florid cemento-osseous dysplasia. PMID- 17333974 TI - Ethics are not hereditary. PMID- 17333975 TI - General guidelines for referring dental patients to specialists and other settings for care. PMID- 17333976 TI - Aspirin-ibuprofen coadministration--FDA issues consumer alert. PMID- 17333977 TI - The vented cast gold crown. AB - Excellence in clinical restorative dentistry may be defined in many ways. Occlusion, esthetics, and morphology are important but none of these factors is more important than longevity. Not all of us will enjoy the clinical success that Dr. Tucker did but the time-tested technique of venting is one way to help prolong the life of a full cast crown. PMID- 17333978 TI - Suturing for optimal soft tissue management. AB - For optimal postsurgical wound healing, non-tension primary wound closure of various soft tissue flaps must be established. Surgical procedures that require clinical flap manipulation (such as those used with traditional periodontal therapy, periodontal plastic cosmetic surgery, hard and soft tissue regeneration, and the excision of pathologic tissue) also require excellent execution and a thorough understanding of the various techniques of surgery, suturing, and the materials currently available for the desired clinical results. This article discusses the rationale behind specific suturing techniques and suture materials to aid the clinician with optimal wound closure. PMID- 17333979 TI - The functional bilaminar impression technique for the distal extension removable partial denture. AB - In recent years, many clinicians have abandoned the time-consuming and technique sensitive border-molded custom impression in favor of a simplified stock tray and irreversible hydrocolloid final impression. However, the master cast obtained by this simplified method often will lead to a completed prosthesis that has inadequate support from the distal extension tissue areas. This article presents a simple, predictable, clinically effective, and readily learned functional bilaminar impression technique that will allow dentists to make an anatomically and functionally supported distal extension removable partial denture. PMID- 17333980 TI - Rationale and protocol for the treatment of non-cavitated smooth surface carious lesions. AB - The decision to restore a smooth surface carious lesion should be based on whether the lesion has cavitated. All non-cavitated lesions should receive preventive therapy aimed at arresting and remineralizing the lesion. Dental caries is a disease based on an imbalance in the equilibrium of ion exchange between the tooth and dental plaque, resulting in a net mineral loss. This equilibrium often can be reversed prior to cavitation, eliminating the need for treating the tooth surgically. Dentists in the U.S. often are apt to restore all lesions that have radiographically penetrated the dentinoenamel junction; however, most of these lesions have not cavitated and can be treated with preventive therapy. Restorations have a limited lifespan and the preparation is enlarged every time a restoration is replaced; as a result, a surgical approach can lead to unnecessary removal of tooth structure and eventually lead to more extensive treatment such as root canal therapy. This article reviews the rationale for deciding when to restore or remineralize non-cavitated lesions on the smooth tooth surfaces in the permanent dentition (and when to provide no treatment at all), what preventive treatment should be administered, and how to determine if the disease has been arrested. PMID- 17333981 TI - The horizontal condylar inclination: clinical comparison of different recording methods. AB - Various types of semi-adjustable articulators (arcon and nonarcon), in combination with different interocclusal recording materials (wax and polyether), have been proposed as an easier alternative to extraoral tracing devices or axiographs. There is no consensus as to which combination is the nearest to the recognized standard extraoral tracing devices. This trial measured differences in performance among four combinations of interocclusal recordings in calculating the horizontal condylar inclination (HCl). The mean HCI measurement obtained by axiograph was 50.3 degrees (SD = 10.2) for the right condyle and 52.5 degrees (SD = 9.3) for the left. Of the four tested combinations, the arcon Whip Mix with wax was most likely to reproduce HCI values obtained using the axiograph. PMID- 17333982 TI - Evaluation of the marginal seal of CEREC 3D restorations using two different luting agents. AB - This in vitro study used two resin cements to evaluate the microleakage of CEREC 3D restorations. An mesio-occluso-distal-lingual (MODL) onlay preparation was placed on an ivorine premolar tooth. Sixty elastomeric impressions of this preparation were used to fabricate resin dies. Imaging propellant was applied to the resin dies. Optical impressions were taken with the CEREC 3 and the CEREC 3D software and used to design and mill 60 onlays. The reliability coefficient was alpha = 0.76 with an examiner agreement rate of 96.4%. Restorations cemented with posterior composite demonstrated a mean microleakage value of 1.46 mm (SD+/- 1.64); by contrast, those restored with dual-cure cement reported a mean microleakage value of 0.21 mm (SD+/-0.57). The difference in microleakage was very highly significant (alpha = 0.001). Posterior composite CEREC 3D restorations cemented with the dual-cure cement showed significantly less microleakage compared to those cemented with posterior composite. PMID- 17333983 TI - Evaluation of root external temperature during the application of ultrasound in removal of intraradicular posts. AB - This study evaluated the temperature rise on external root surfaces by simulating the removal of metallic posts by applying ultrasound, with or without refrigeration and at different times. The crowns of 30 healthy maxillary central incisors were removed and the roots were treated endodontically. The prosthetic spaces were prepared and impressions were taken with self-curing acrylic resin. After casting with a copper-aluminum alloy, the posts were blasted with aluminum oxide and cemented with resin cement. The specimens were randomly assigned to three groups according to the time of ultrasonic vibration (30, 60, or 120 seconds) and were subdivided into two groups, those cooled with and without water refrigeration. A thermocouple connected to a digital thermometer was positioned on the root external surface and the maximum temperature was recorded. Data were submitted to ANOVA and Tukey's test. Analysis of the results revealed statistical difference among groups (p < 0.01). Ultrasound (with and without water spray) increased root temperature significantly, reaching values of more than 50 degrees C. The exception was the group that used 30 seconds of ultrasound with refrigeration; root temperature reached 35.4 degrees C, making it the only tested condition that remained below the critical value (50 degrees C). PMID- 17333984 TI - Use of a thermoplastic resin stayplate as an alternative to an acrylic stayplate: a case report. AB - The fabrication of a chrome-cobalt metal partial denture is the standard in terms of removable partial dentures; alternative treatment includes an acrylic partial denture (such as a transitional stayplate). While these types of removable devices have been used successfully for many years, they also have disadvantages. Thermoplastic resin materials are a promising alternative for fabricating a transitional stayplate with improved results. A search of the literature indicated a scarcity of research concerning this material. This article presents a case report in which this material was utilized. PMID- 17333985 TI - Simple bone cyst: possible misdiagnosis in periapical pathology. AB - Simple bone cysts are non-neoplastic bone lesions, classified as intraosseous pseudocysts without epithelial lining, that can be empty or filled by fluid and display uncommon clinical and radiographic features. This article presents an unusual case of a simple bone cyst with clinical and radiographic features similar to chronic apical periodontitis. A general dentist referred an 18-year old man for endodontic treatment after the patient complained of pain in the mandibular right second molar, which displayed a significant bony radiolucency. Chronic periapical lesion was excluded after detailed clinical and radiographic examinations. During surgical exploration, an empty bone cavity was observed and curetted before wound closure. One year later, complete healing was observed. PMID- 17333986 TI - Intraosseous angiomyoma of the mandible. AB - Leiomyoma is a benign smooth muscle tumor that usually is found in the uterus, gastrointestinal tract, or skin. It appears infrequently in the oral cavity. Intraosseous leiomyomas are rare; to date, only 14 cases have been reported in the English-language literature. Gnathic leiomyoma occurs more commonly in the posterior mandible as an asymptomatic swelling with variable radiographic appearance. Microscopically, 53% of gnathic leiomyomas have a prominent vascular component that warrants a diagnosis of angiomyoma. Surgical excision is the treatment of choice. This article describes the clinical-pathological features of an exceptional intraosseous angiomyoma of the mandible. PMID- 17333987 TI - Surgical and orthodontic conduct in the treatment of mesiodens: a case report. AB - This article reports a clinical case involving an 8-year-old boy with two mesiodentes. The supernumerary teeth caused both a functional alteration (malocclusion) and an esthetic one (interincisal diastema), both of which affected his quality of living. Surgical removal of the supernumerary teeth and orthodontic follow-up was proposed, in agreement with the treatment established in the literature. This treatment produced satisfactory results in terms of both esthetics and functionality. PMID- 17333988 TI - Extrafollicular adenomatoid odontogenic tumor: a case report. AB - The adenomatoid odontogenic tumor (AOT) is a benign, non-invasive lesion with a slow but progressive growth. This tumor has three variants: follicular, extrafollicular, and peripheral. The extrafollicular type is an intraosseous lesion that is not associated with unerupted teeth. Radiographically, it appears as a well-defined, unilocular, round or ovoid radiolucency with multiple, small, irregular radiopaque foci. Microscopically, it is characterized by nodules of cuboidal or columnar epithelial cells that form nests, rosette or duct-like structures (with minimal stromal connective tissue), and acellular calcifications. This article presents the case of a 35-year-old man with a lesion on the anterior mandible. Clinical and radiographic features indicate that this lesion is an extrafollicular variant of AOT. PMID- 17333989 TI - Maximum cumulative doses of sedation medications for in-office use. AB - The AGD acknowledges that dentists may need an additional permit to perform the procedure described in this article. Many states require dental practitioners to have additional or advanced training in order to perform enteral sedation. In some states, practitioners must have an i.v./conscious sedation permit before they are allowed to titrate (dose) oral medication. The ADA does not believe that oral medication can be titrated (dosed) without an i.v. sedation license. The AGD has adopted and published a white paper on sedation issues, which appeared in the September-October 2006 issue of General Dentistry. The AGD encourages continuing education in sedation modalities for general dentists. Oral conscious sedation (OCS) is an increasingly common practice in dentistry and is at the forefront of evolving state regulations. At the center of the OCS controversy is the oral titration of medications. Most medications available for OCS are used in an "off label" manner and have no determined maximum recommended dosage for that purpose. This article proposes cumulative maximum dosing guidelines for in-office OCS, with an emphasis on triazolam. PMID- 17333990 TI - Commercial soft drinks: pH and in vitro dissolution of enamel. AB - Most soft drinks are acidic in nature and exposure to these drinks may result in enamel erosion. This study sought to measure the pH of 20 commercial brands of soft drinks, the dissolution of enamel resulting from immersion in these drinks, and the influence of pH on enamel loss. Comparison of the erosive potential of cola versus non-cola drinks as well as regular sugared and diet versions of the same brands was undertaken. The pH was measured immediately after opening the soft drink can. Enamel slices obtained from freshly extracted teeth were immersed in the soft drinks and weighed at baseline and after 6, 24, and 48 hours of immersion. Non-cola drinks had significantly higher pH values than cola drinks but showed higher mean percent weight loss. By contrast, sugared versions of the cola and non-cola drinks showed significantly lower pH values and higher mean percent weight loss than their diet counterparts. The pH value of the soft drink did not have a significant influence on the mean percent weight loss (r = -0.28). Prolonged exposure to soft drinks can lead to significant enamel loss. Non-cola drinks are more erosive than cola drinks. Sugared versions of cola and non-cola drinks proved to be more erosive than their diet counterparts. The erosive potential of the soft drinks was not related to their pH value. PMID- 17333991 TI - Salivary analysis in the diagnosis and treatment of breast cancer: a role for the general dentist. AB - Saliva testing is an attractive area of research for the general dentist, as it offers a great opportunity to utilize an easily accessible fluid for the diagnosis of disease. Diseases that may be difficult to detect, such as breast cancer, are an area of particular interest. Breast cancer is the second leading cause of death among women in the U.S. and early detection is critical to patient survival. Frequent and inexpensive testing is the key to early detection. The general dentist is in the perfect position to take salivary samples from patients during routine checkups or procedures and to refer patients depending on the results. PMID- 17333992 TI - Multiple mucosal lesions. Erythema migrans. PMID- 17333993 TI - Painless gingival mass. Peripheral giant cell granuloma. PMID- 17333994 TI - Why all the quarreling over evidence-based dentistry? PMID- 17333995 TI - Restoring the fractured root-canal-treated maxillary lateral incisor: in search of an evidence-based approach. AB - OBJECTIVE: To demonstrate the existing difficulties and variability in the application of evidence-based dentistry by comparing the recommendations made by 4 dental experts for the treatment of a fractured tooth. METHOD AND MATERIALS: A case presentation was given to 4 specialists, who were asked to independently develop and explain their personal favorite treatment strategy, based on the best available external evidence and their clinical expertise. The entire case was then reviewed by an expert in evidence-based medicine and discussed with the first author. RESULTS: Each of the 4 experts relied on different articles in justifying their clinical decisions. The minimal overlap in the literature they cited largely explains the different treatment suggestions: While the endodontist preferred a metal post-and-core and a porcelain-fused-to-metal (PFM) crown, both the operative dentist and the prosthodontist opted for a glass-fiber post/fiber reinforced resin composite post. The perio-prosthodontist recommended a PFM crown with either a direct or indirect post and core. The citation analysis revealed that little high-quality information is available about what would be the best therapy for horizontal fractures of root-canal-treated anterior teeth. CONCLUSIONS: This article illustrates that, although it is now common practice in dentistry to base clinical decision making on external evidence from the literature, search strategies and the resulting clinical recommendations still vary greatly. PMID- 17333996 TI - Immediately loaded short implants: analysis of a case series of 133 implants. AB - OBJECTIVE: To perform a retrospective study on the success of immediately loaded short implants (ie, length < 10 mm). METHOD AND MATERIALS: From January 1995 to October 2004, 133 short implants were inserted and immediately loaded. Multiple implant systems were used, with a mean follow-up of about 4 years. Only 3 of the 133 implants were lost (ie, a survival rate of 97.7%), and no statistically significant differences were found among the studied variables; no or reduced marginal bone loss was considered as an indicator of the success rate when evaluating the effects of several factors with the use of a general linear model. RESULTS: By using the survival rate, no differences were detected among the studied variables. On the contrary, the analysis of the success rate by means of a general linear model showed that wider (diameter > 3.75 mm) and longer (length = 10 mm) implants were related to a lower delta insertion abutment junction (or marginal bone loss) and thus a better outcome. CONCLUSION: Immediately loaded short implants had a high survival rate and success rate similar to those reported in previous studies of 2-stage procedures. Immediate loading of short implants can be considered a reliable technique, although a higher marginal bone loss was to be expected when narrow (diameter < or = 3.75 mm) and shorter (length < 10 mm) implants were used. PMID- 17333997 TI - Management of root-fractured incisors in a 12-year-old followed with implant treatment 7 years after traumatic injury: a case report. AB - Trauma to the maxillary anterior teeth is a frequent occurrence in children and adolescents. Coronal fractures may now be successfully treated by reattachment of the fractured portions with the latest enamel and dentin bonding agents. Root fractures present with more challenging problems. Conservative and proper management of root fractures will greatly help the preservation of the alveolar bone to facilitate subsequent implant placement. This is a case report of such management spanning over many years, from adolescence to adulthood, when the implants were placed for the final esthetic ceramic crowns. PMID- 17333998 TI - Oral health and dental treatment of patients with renal disease. AB - OBJECTIVES: To outline aspects that need consideration in the dental office when treating patients with renal disease and to present data on the oral health parameters of patients during the different phases of their renal disease during a 10-year follow-up period. Differences in clinical and salivary study parameters during the course of treatment of the renal disease were expected to occur. METHOD AND MATERIALS: Altogether, 39 patients with chronic renal failure were examined for dental health. Nine patients (mean age 50.8 years) were followed for 10 years through predialysis, dialysis, and posttransplant stages. The patients were examined clinically and radiographically and by analyzing the biochemical constituents of saliva. Patients' perceptions of oral health were recorded using structured questionnaires. RESULTS: No statistically significant differences were observed in the clinical parameters studied during the follow-up period. However, analyses of saliva components after renal transplantation showed significant improvement compared with components found during the predialysis stage. For example, median salivary albumin concentration, which describes the leakage of serum components to saliva, was 399 microg/mL at the predialysis stage, 353 microg/mL at the dialysis stage, and 181 .g/mL at the posttransplant stage. CONCLUSIONS: From the oral health point of view, the outcome was better than anticipated. The lower salivary albumin values after kidney transplantation may reflect the improvement of patients' health during the course of the treatment. PMID- 17333999 TI - Central ossifying fibroma: an analysis of 20 cases and review of the literature. AB - Central ossifying fibroma is the most common benign fibro-osseous neoplasm of the jaw. It is not easy to diagnose ossifying fibroma because its clinical, radiographic, and histologic criteria often overlaps with other fibro-osseous lesions. Based on the analysis of 20 cases, this article describes all the manifestations of central ossifying fibroma and some of the differences with the so-called juvenile active ossifying fibroma. Photographs and radiographs of 2 cases showing a number of all the clinical and radiographic features of central ossifying fibroma are presented. The surgical procedure of these cases is also illustrated. PMID- 17334000 TI - Apical sealing ability of 2 epoxy resin-based sealers used with root canal obturation techniques based on warm gutta-percha compared to cold lateral condensation. AB - OBJECTIVE: To evaluate the apical sealing ability of 2 epoxy resin-based root canal sealers used with 2 different warm gutta-percha obturation techniques and cold lateral condensation. METHOD AND MATERIALS: The root canals of 72 freshly extracted single-root incisors were prepared and randomly assigned to 6 experimental groups. Root canal fillings were performed using either cold lateral condensation, warm vertical condensation, or Thermafil obturators with EndoRez or AH Plus as sealer. After root canal filling, the teeth were stored in 5% methylene blue solution for 7 days. Linear dye penetration was measured in bisected specimens by a calibrated investigator using a light microscope. RESULTS: Statistical analysis revealed significantly higher penetration depths in groups where EndoRez was used (P < .05, Tukey test). Regarding the different obturation techniques, the least amount of dye penetration was observed for AH Plus and EndoRez when warm vertical condensation was used. CONCLUSION: The results of this study indicate that the apical sealing ability of EndoRez is not as effective as that of AH Plus. Thermafil obturators and warm vertical condensation achieved seals with low dye penetration depth. The use of these techniques might decrease the risk of apical leakage. PMID- 17334001 TI - Prevention of oral and salivary gland impairment in irradiated adolescent patients with head and neck cancer: a suggested protocol. AB - Patients with head and neck cancer receive high doses of localized irradiation therapy, which results in destruction of salivary gland secretion ability. Pilocarpine hydrochloride was shown to have some beneficial effect on quality of life of these patients. Most studies concentrated on adult patients with head and neck cancer with no reference to adolescents. This case report demonstrates the long-term beneficial effect of pilocarpine hydrochloride in maintaining sufficient saliva, oral soft tissue integrity, and caries-free status in an adolescent cancer patient who received a total radiation dose of 6,000 cGy. A suggested protocol for management of irradiated adolescent patients with head and neck cancer is offered. PMID- 17334002 TI - Successful use of a single-retainer all-ceramic resin-bonded fixed partial denture for replacement of a maxillary canine: a clinical report. AB - This clinical report describes the prosthodontic treatment of a 60-year-old woman to close an edentulous space in the region of the maxillary canine. Single retainer resin-bonded fixed partial dentures (FPD) have shown satisfactory results in different studies. Recent in vivo studies have shown excellent results for all-ceramic anterior FPDs after 5 years. In the present situation, a cantilevered all-ceramic FPD chosen to replace a missing maxillary canine showed success at the 2.5-year follow-up. Special attention was given to functional and minimal restorative considerations. The use of single-retainer all-ceramic FPDs is discussed. The present case does not represent a routine and well-documented approach for the replacement of a missing maxillary canine. Rather, it is a rarity that was successful because of space availability, present occlusal scheme, and patient cooperation. Implant-supported restorations always should be considered as the first treatment option in such a clinical situation. PMID- 17334003 TI - Levels of metalloproteinase-2 and -9 and tissue inhibitor of matrix metalloproteinase-1 in gingival crevicular fluid of patients with periodontitis, gingivitis, and healthy gingiva. AB - OBJECTIVE: To compare the levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in patients with gingivitis and periodontitis and in healthy controls. METHODS: Levels of MMP 2, MMP-9, and TIMP-1 were determined by ELISA in patients with healthy gingiva (n = 16), gingivitis (n = 18), and periodontitis (n = 25). The subjects with periodontitis were examined before and 1 month after basic periodontal therapy. RESULTS: Slightly higher concentrations of MMP-9 were observed in patients with periodontitis but without statistical significance. MMP-2 was found to be slightly diminished in these patients. The lowest concentrations of MMP inhibitor (TIMP-1) were observed in patients with periodontitis, in whom the concentrations increased after periodontal treatment. CONCLUSION: The reduction in TIMP-1 concentrations in disease situations suggests a breakdown of the balance between the amount of MMPs and their inhibitor. PMID- 17334004 TI - Central giant cell granuloma of the mandible in a 7-year-old boy: a case report. AB - Central giant cell granuloma is a relatively uncommon benign bony lesion of a variably aggressive nature. This paper presents the case of a 7-year-old boy with central giant cell granuloma in the anterior mandible. In children with mixed dentition, a pathologic lesion could be the underlying cause of regular tooth mobility and exfoliation of primary teeth and can easily be overlooked, especially in cases that are not accompanied by an obvious bony expansion. The clinician needs to be aware of possible oral pathology when tooth mobility and displacement are present, and central giant cell granuloma should be considered in the differential diagnosis for children with maligned and mobile teeth. PMID- 17334005 TI - Emerging retroviral regimens for the developing world--"stop AIDS; keep the promise". PMID- 17334006 TI - Nevirapine versus efavirenz based antiretroviral treatment in naive Indian patients: comparison of effectiveness in clinical cohort. AB - OBJECTIVE: Our objective was to compare immunologic effectiveness of nevirapine and efavirenz based antiretroviral therapy in antiretroviral naive HIV-1 infected Indian patients. DESIGN AND METHODS: Study was an observational, non-randomized, longitudinal cohort. Antiretroviral naive HIV-1 infected patients receiving efavirenz + 2NRTI (n=254) and nevirapine + 2 NRTI (n=857) from April 2000 were followed up at two tertiary care HIV clinics at Ahmedabad and Pune. Patients were followed up clinically monthly and CD4 was carried out every 3 monthly. All patients were examined for various side effects as well as development of various OIs. Data were analyzed using standard statistical methods. RESULTS: Baseline characteristics for both the groups (NVP and EFV) were comparable. In the random effects model, there was an increase of 40.97 (p < 0.05) units of CD4 cell counts with an unit increase in time in the NVP arm as against a 44.75 (p < 0.05) units of increase in CD4 cell counts in the EFV group with a unit increase in time, which is significant for both groups. However, at any given point of time there was no difference in the rate of increase of CD4 count between the two treatment arms (p = 0.58). Hypersensitivity reaction (6.6% in NVP vs. 2.32% in EFV, p = 0.0146) and hepatitis (3.2% in NVP vs. 0% in EFV, p = 0.0085) were more common with nevirapine, while neurologic disturbances (0.93% in NVP vs. 20.15% in EFV, p = 0.0001) were more common with efavirenz. Incidence of distal sensory neuropathy and lipid abnormalities was similar in both the groups. CONCLUSION: Use of NVP and EFV based HAART in antiretroviral naive Indian patients led to significant and durable rise in CD4 cell count. Although observational and non-randomized, our study showed equivalent immunological response amongst NVP and EFV based HAART which is in line with the results of the 2NN study. PMID- 17334007 TI - Cushing's disease: management outcome in a tertiary care centre. AB - Cushing's syndrome (CS) can pose a challenge in diagnosis and management. Successful management of CS needs accurate localization of the site of lesion. Present article narrates experience of a single center dealing with large number of patients with CS and highlights difficulties in diagnosis as well as management of Cushing's disease (CD). METHODS: All patients with CD, where histopathological lesion was documented were studied to evaluate yield from different diagnostic tests. Diagnosis was established by standard 2 days low dose dexamethasone suppression test. Localization of the lesion was achieved with high dose dexamethasone suppression (HDDS) and imaging. Inferior petrosal sinus sampling (IPSS) was used whenever diagnosis was not arrived at with the standard tests. RESULTS: Out of 100 consecutive patients of CS seen, 69 had CD. HDDS had sensitivity of 70% and specificity of 99% in localizing the lesion. Imaging localized the lesion in 68% of patients. Combination of HDDS and imaging localized the lesion in 90% of patients. IPSS helped to localise the lesion in remaining 10% of patients. Transsphenoidal surgery was carried out in 65/69 patients. Cure rate for microadenoma was 77% and for macroadenoma was 36%. Mortality and morbidity rate was 7% and 7% respectively. 2nd TSS, radiotherapy and bilateral adrenalectomy were the additional modalities used in that order, in patients who were not cured or who had recurrence. CONCLUSION: Management of CS is best carried in a center where a team of experienced endocrinologist and neurosurgeon is available. PMID- 17334008 TI - Subjective global assessment of nutritional status of patients with chronic renal insufficiency and end stage renal disease on dialysis. AB - OBJECTIVES: (1)To assess the nutritional status of chronic renal insufficiency (CRI) and dialysis patients using the subjective global assessment (SGA) method. (2) To validate SGA in assessing the nutritional status of this group of patients. PARTICIPANTS: The nutritional status of 81 patients was evaluated using dietary recall, anthropometry, biochemical parameters and SGA. There were 51 males and 30 females. Their mean +/- SD age was 53.8 +/- 14.3 years. There were 27 patients with (CRI) on conservative management, 38 patients with end stage renal disease (ESRD) on maintenance hemodialysis (HD) and 16 patients with ESRD on continuous ambulatory peritoneal dialysis (CAPD). METHODS: SGA was done using seven variables derived from medical history and physical examination. Each variable was scored from 1-7 depending on the severity. The SGA scores were correlated with the standard methods. RESULTS: Thirteen (48%) patients with CRI, 22 (58%) patients on HD and 8 (50%) patients on CAPD were malnourished. It was seen that the dietary protein & calorie intake and serum albumin level did not correlate well with the SGA scores. The anthropometric measures correlated with the SGA scores (Skinfolds and SGA r = 0.2, MAC and SGA r = 0.5 and MAMC and SGA r = 0.5). CONCLUSION: Malnutrition is an important complication in CRI patients and ESRD patients on dialysis. SGA is a reliable method of assessing nutritional status. Most important is the fact that it can detect the changing trend of nutritional status, which may be missed by one-time anthropometry and biochemical methods. PMID- 17334009 TI - Optimising primary headache management. AB - Despite the fact that headache is one of the commonest of medical complaints seen in practice, most headache patients continue to be suboptimally managed. Probably because recent advances in the field of headache are written about more in specialty journals, many physicians even today feel that nothing much can be done for their headache patients! And, since more than 90% of headaches seen in practice are primary headaches, we need to realize that there is enough evidence now to show that primary headaches are a potentially treatable biological problem. It is therefore important that we do not err in the diagnosis and choice of the right drug options. This article discusses some of the reasons for suboptimal management of primary headaches and suggests measures to avoid these 'Pitfalls'. Secondary headaches where there is an underlying cause identifiable on examination or investigation are outside the scope of this review. PMID- 17334010 TI - Pregnancy in Ehlers-Danlos syndrome. PMID- 17334011 TI - Osteopoikilosis. PMID- 17334012 TI - Caspofungin: a major breakthrough in treatment of systemic fungal infections. AB - Invasive fungal infections are difficult to eradicate especially in immuno compromised host. Amphotericin B and voriconazole have been the mainstay of treatment but both have significant toxicity. Caspofungin belongs to a new class of antifungal agents, the echinocandins. It acts on the fungal cell wall by selective inhibition of beta-(1,3)-D-glucan syntheses, which is not present in mammalian cells. In vitro data and experimental studies have demonstrated that it has antifungal activity against yeasts of the genus Candida (including those resistant to amphotericin B and azoles), severe species of filamentous fungi, including aspergillosis and certain dimorphic fungi. As an empirical antifungal therapy in neutropenic patients, it has comparable clinical efficacy but superior tolerability compared with liposomal amphotericin B. In patients with invasive candidiasis, it is as effective as amphotericin B deoxycholate. In addition, it showed a significantly superior safety profile. Same has been shown in patients with oropharyngeal/oesophageal candidiasis. In patients with invasive aspergillosis refractory to or intolerant to other antifungal agents, 45% showed a partial or complete response to Caspofungin given as a salvage treatment. Caspofungin is cidal for all Candida species and is static against Aspergillus species. It also possesses activity against Pneumocystis jiroveci. In vitro and in animals, Caspofungin shows additive or synergic antifungal activity with amphotericin B and triazoles. Recently, it's use in paediatric patients, including after bone marrow transplantation, has also been shown to be safe. With compare to other antifungal agents known to be effective in systemic fungal infections, Caspofungin has the best safety profile, tolerability with very low potential for drug interactions. This makes Caspofungin an interesting and extremely valuable new antifungal agent that broadens the available therapeutic armamentarium for the treatment of systemic fungal infections. PMID- 17334013 TI - Primary Sjo-gren's syndrome presenting with distal, renal tubular acidosis and rhabdomyolysis. AB - Primary Sjogren's syndrome (PSS) is rare in India. Clinically manifest renal disease in PSS is uncommon and is usually an autoimmune tubulointerstitial nephritis presenting with distal renal tubular acidosis (dRTA) or a urinary concentrating defect. Hypokalemic paralysis due to dRTA in PSS is rare but well documented in medical literature. Rhabdomyolysis as a consequence of hypokalemia in PSS is exceptional. We report a case of PSS with dRTA and rhabdomyolysis causing prolonged respiratory failure and quadriparesis. PMID- 17334014 TI - Gatifloxacin induced abnormalities in glucose homeostasis in a patient on glimepiride. AB - Gatifloxacin, a commonly prescribed antimicrobial can produce profound hypoglycemia and disturbances in glucose homeostasis especially in diabetes patients on sulphonylureas. Also new onset disturbances in glucose homeostasis can occur in patients who were unaffected by the previous use of gatifloxacin. Therefore it is suggested that gatifloxacin is better avoided in patients with diabetes and in the elderly. PMID- 17334015 TI - Gatifloxacin-induced severe hypoglycemia in a patient with type 2 diabetes mellitus. AB - A case of Gatifloxacin-induced severe and recurrent hypoglycemia in 62-year-old type 2 diabetic patient is presented. Possible mechanisms responsible for hypoglycemia are discussed and the literature on the subject is reviewed. PMID- 17334016 TI - Delayed syndrome in carbon monoxide poisoning. AB - Acute carbon monoxide poisoning can lead to delayed manifestations. This has been called post-interval syndrome, which can present after an apparent period of normalcy following acute poisoning. We are reporting a patient who had an accidental exposure to carbon monoxide and presented later with all the manifestations of delayed poisoning. The various clinical manifestations and imaging findings are discussed. A delay in recognition in the acute stage can predispose to development of the post-interval syndrome. PMID- 17334017 TI - Nevirapine-induced fulminant hepatitis. AB - Nevirapine induced hepatotoxicity is known but fatality is rare. We report a case of a young individual who developed nevirapine (NVP) induced fatal hepatitis without apparent risk factors or preceding rash. Exacerbation of underlying silent chronic liver dysfunction possibly contributed to the fatal outcome. This case stresses the need for careful evaluation, regular monitoring and prompt omission of drug on suspicion of hepatotoxicity. PMID- 17334018 TI - Coeliac sprue--new frontiers in diagnosis and role of capsule endoscopy. AB - The diagnosis of Coeliac Disease (CD) till now was done based on histological findings and response to gluten- free diet. Recently, Serological tests like IgA anti-endomysial antibodies (AEA) IgA tissue-transglutamin (tTG), IgA antigliadin antibodies (AGA) and IgG AGA antibodies have been added to the armamentarium. Being a small bowel disorder the upper GI endoscopy and colonoscopy are not of much help. The advent of Capsule Endoscopy (CE) which scans the entire small bowel and gives highly magnified and detailed view of mucosa has facilitated the diagnosis of CD to great extent. Moreover, CE is painless, well tolerated and safe diagnostic procedure. This article presents new frontiers in diagnosis, role of capsule endoscopy, and the first case of diagnosis of CD by CE in India. PMID- 17334019 TI - Nicolaas Tulp (1593-1674). Postal stamps issued on Nicolaas Tulp. Anatomy lessons of Dr. Tulp, stamp Togo, 1968; details, from the same painting, stamp--Gambia, 2001. PMID- 17334020 TI - Acquired von Willebrand's disease associated with gastrointestinal angiodysplasia and monoclonal gammopathy. PMID- 17334021 TI - Leptospirosis in Chennai--changing clinical profile. PMID- 17334022 TI - A proof of concept, preliminary study to determine the effect of Yogasnas in controlling type 2 diabetes mellitus in newly detected subjects (when compared to metformin monotherapy). PMID- 17334023 TI - Challenges in clinical education. PMID- 17334024 TI - An ethicist's commentary on increased cost of proper shipping. PMID- 17334025 TI - Canada's 1st accredited veterinary dentistry residency program. PMID- 17334026 TI - A survey on finishing pig mortality associated with porcine circovirus diseases in Quebec. PMID- 17334027 TI - Neurotoxic cyanobacterium (blue-green alga) toxicosis in Ontario. PMID- 17334028 TI - Warm weather transport of broiler chickens in Manitoba. II. Truck management factors associated with death loss in transit to slaughter. AB - This observational study was conducted to identify the cause of death and load level factors associated with mortality in 1 090 733 Manitoba broiler chickens transported to slaughter in spring and early summer. Death loss in transit was 0.346% and accounted for 19% of the total carcass condemnation. The death loss pattern was clearly bimodal, with a low death loss in 180 of 198 shipments. Cumulative death loss during the growing phase of production was consistently associated with increased transport mortalities in load level models and when comparing high death loss with low death loss truckloads. High ambient temperature at the time of slaughter and loading density of the truck were the major factors associated with exceptional death loss. PMID- 17334029 TI - Canadian veterinarians' use of analgesics in cattle, pigs, and horses in 2004 and 2005. AB - Anecdotal evidence suggests that many veterinarians may not use analgesics in livestock for routine surgical procedures or painful disease states. To investigate this, we conducted a national mail survey of a random sample of 1431 Canadian veterinarians (response rate, 50.1%). Questions primarily concerned veterinarians' analgesic usage for common surgeries and medical conditions in beef and dairy cattle, pigs, and horses, and attitudes toward pain management. More than 90% of veterinarians used analgesic drugs for equine surgeries, for cesarean section in sows and cows, and for bovine claw amputation and omentopexy. However, in these and other categories, the analgesics used were often inadequate, and many veterinarians did not give analgesics to young animals. When castrated, < 0.001% of piglets received analgesia, compared with 6.9% of beef calves and 18.7% of dairy calves < or = 6 mo of age, 19.9% of beef calves and 33.2% of dairy calves > 6 mo of age, and 95.8% of horses. Respondents largely agreed that there are no long-acting, cost-effective analgesics available for use in livestock (median rating 8/10; interquartile range 4-9), and that the long or unknown withdrawal periods of some drugs outweighed the benefits of using them (median rating 7/10; interquartile range 4-9). The results indicate an urgent need for veterinarians to manage pain in livestock better. Continuing education would help, as would an increase in the number of approved, cost-effective analgesic drugs with known withdrawal periods. PMID- 17334030 TI - The use of veterinary cuttable plates for carpal and tarsal arthrodesis in small dogs and cats. AB - The objective of the study was to evaluate, retrospectively, carpal and tarsal arthrodesis in small dogs and cats by using veterinary cuttable plates in 6 animals and comparing those with arthrodesis stabilized with other implants in 9 animals. Veterinary cuttable plates were used for 1 pancarpal, 2 partial tarsal, and 3 pantarsal arthrodeses. Other implants were used to stabilize 1 pancarpal, 6 partial tarsal, and 2 pantarsal arthrodeses. In the veterinary cuttable plates group, complications included 2 cases with pressure sores and 1 case with screw loosening. One animal was lost to follow-up and 4 of the remaining 5 were always weight-bearing. In the other group, there were 2 cases with pressure sores, 1 case with dermatitis, and 2 cases with pin migration. Six out of 9 animals were always weight-bearing. The use of veterinary cuttable plates appears to be a suitable option with a good clinical outcome. PMID- 17334031 TI - Prevalence of perioperative arrhythmias in 50 young, healthy dogs. AB - The objective of this study was to assess the type and frequency of cardiac dysrhythmias occurring after routine ovariohysterectomy or orchidectomy in young, healthy dogs by using 2 anesthetic protocols (group I: propofol and isoflurane; group II: thiopental and halothane). Fifty dogs under 2 years of age, judged to be clinically normal by physical examination and standard electrocardiography, were evaluated by using 24-hour ambulatory electrocardiography. The most common dysrhythmias in the postoperative period were 2nd degree atrioventricular block (44%), ventricular premature complexes (44%), and atrial premature complexes (32%). For study purposes, more than 100 ventricular or atrial premature complexes per 24 hours, or any occurrence of R-on-T phenomenon, ventricular or atrial tachycardia were classified as clinically significant arrhythmias. Significant arrhythmias were observed in 9 dogs in the postoperative period, 5 of which were in group I and 4 in group II. All of these dogs were under 1 year of age. The R-on-T phenomenon occurred in 4 dogs in group II and 1 dog in group I. Results from this study show that significant arrhythmias, including R-on-T phenomenon, can occur in the perioperative period in young, healthy dogs undergoing routine surgeries with both protocols used. PMID- 17334033 TI - Treatment of hypernatremia in neonatal calves with diarrhea. AB - Five hypernatremic, diarrheic, neonatal calves were treated mainly by the intravenous administration of 5% dextrose alone or with isotonic sodium bicarbonate. All calves recovered without complications. The average reduction rate of serum sodium concentration was about 4 times that recommended and has not been tried successfully before in hypernatremic scouring calves. PMID- 17334032 TI - Fetal well-being assessment in bovine near-term gestations: current knowledge and future perspectives arising from comparative medicine. AB - Cloning technology is associated with multiple losses throughout pregnancy and in the neonatal period. Any maternal or fetal disease can compromise pregnancy. A paucity of data are available on bovine fetal well-being in late pregnancy; development of well-being assessment methods might augment early diagnosis of abnormal pregnancy or fetal distress, allowing early intervention. This review presents the current knowledge on fetal well-being based on bovine, ovine, equine, and human studies, as well as interesting research parameters that have been studied in other species and not yet investigated in cattle. Transabdominal ultrasonography allows for diagnosis of large placentomes and hydrallantois that frequently accompany clone pregnancies. Fetal inactivity or large hyperechoic particles imaged within the fetal annexes are associated with fetal distress or death, and should be reassessed to confirm compromised pregnancy. Measurements of different fetal parameters (thoracic aorta, metacarpal or metatarsal thickness) could be reliable tools for early detection of the large offspring syndrome commonly found in cloned calves. PMID- 17334034 TI - Management of airway difficulties during induction of general anesthesia in an American miniature horse with dwarfism. AB - This report describes previously unreported upper airway abnormalities encountered in a 5-month-old American miniature horse colt presented for elective surgery. Caution should be exercised when administering general anesthesia or heavy sedation to individuals of this breed that present with multiple congenital abnormalities. PMID- 17334035 TI - Pharyngeal neuromuscular dysfunction associated with bilateral guttural pouch tympany in a foal. AB - A 2-month-old warmblood filly was presented for a 1-week history of a large, nonpainful, fluctuant swelling of the parotid and laryngeal area. Bilateral guttural pouch tympany was diagnosed. Surgical correction resolved the guttural pouch tympany; however, postoperative pharyngeal neuromuscular dysfunction developed. PMID- 17334036 TI - The art of apology. PMID- 17334037 TI - What's new in orthopedics. PMID- 17334038 TI - Diagnostic dermatology. Paraneoplastic syndrome. PMID- 17334039 TI - Veterinary diagnostic imaging. Lobar hepatic infarction with hemorrhage, secondary to a condition of chronic lymphocytic portal hepatitis with dissecting fibrosis and abundant copper accumulation. PMID- 17334040 TI - Immunoblastic lymphoma of germinal center origin in a cat. PMID- 17334041 TI - [Acta Reumatologica Portuguesa: new horizons]. PMID- 17334042 TI - [Annexin-1: 2nd messanger of the anti-inflammatory actions of glucocorticoids]. AB - Glucocorticoids have important immunosupressive properties, being used as anti inflammatory therapeutic agents in a wide range of inflammatory and auto-immune pathologies. One of the best studied mechanisms by which glucocorticoids exert most of their anti-inflammatory actions involves the induction of the synthesis and the secretion of the mediator and effector protein annexin 1 (ANXA1). Here we review the molecular and cellular pathways involved on the glucocorticoid-induced synthesis and secretion of ANXA1 in a variety of cell types. Since its discovery as an anti-phospholipase A2 protein, ANXA1 has come a long way to encompass a wide range of cellular effects, the most relevant ones being those that directly modulate the inflammatory response. The results presented in this review open the way to further pharmacological studies which will allow the identification of the role of ANXA1 in inflamatory pathologies, namely rheumatoid arthritis. PMID- 17334043 TI - [Rheumatic manifestations and neoplasms]. AB - Links between rheumatic manifestations and neoplasms are today an evidence. Certain syndromes have epidemiologic studies confirming strong association with malignancy, such as dermatomyositis and polymyositis, hyperthrophic osteoarthropathy and Lambert - Eaton myasthenic syndrome. These disorders may mimic idiopathic conditions, difficulting diagnosis. Besides that, longstanding rheumatic syndromes may, in their course, behave like premalignant conditions, as a result of their pathophysiology or drugs used in their treatment. The mechanisms whereby the neoplasm leads to rheumatic symptoms are: direct invasion of the musculoskeletal system, synovial reaction of justa-articular bony or capsular carcinomatous, secondary gout and paraneoplastic manifestations. Neoplasms constitute an important admission cause in Internal Medicine wards and rheumatic manifestations are common causes of Internal Medicine and Rheumatology appointments. The objective of the present work is to review the literature concerning rheumatic syndromes more frequently associated with malignancy, characterizing features that may suggest the presence of a hidden neoplasm as well as the potential diagnostic and prognostic value of their presence in malignant diseases. PMID- 17334044 TI - Lymphocyte ceruloplasmin and Behcet's disease. AB - INTRODUCTION: Behcet's disease (BD) is a rare chronic inflammatory disorder of unknown aetiology. However, it has been postulated that a dysregulation of the prooxidant/antioxidant balance may be important to its pathogenesis. Ceruloplasmin (CP) is an acute phase protein expressed at the surface of peripheral blood lymphocytes (PBL) with antioxidant properties and with a relevant role in iron (Fe) metabolism. OBJECTIVES: To study CP expression at the surface of PBL (PBLCP) in patients with BD. MATERIAL AND METHODS: We measured serum CP and PBLCP obtained from BD patients (n=10) and respective controls (n=10) using nephelometry and flow cytometry techniques, respectively. Additionally, haematological parameters, biochemical Fe metabolism markers [serum Fe, serum ferritin, serum transferrin, total Fe binding capacity (TIBC), transferrin saturation] and non-specific markers of inflammation [serum C reactive protein (CRP), beta2-microglobulin] were measured in all individuals. RESULTS: Despite the absence of significant differences between the two study groups when comparing serum CP, a significant difference in PBLCP was found in BD patients mainly due to a significant decrease of CP expression at the surface of CD3-CD56+ lymphocytes. Also, a significant decrease of PBLCP was observed in patients treated with azathioprine compared to patients that were not being treated with this drug. CONCLUSIONS: According to this study, we suggest that the significant decrease of PBLCP observed in BD patients might be due to azathioprine treatment and not directly related to the pathophysiology of BD. PMID- 17334045 TI - [Eating habits and life styles in a Portuguese population--protective and risk factors for osteoporosis]. AB - BACKGROUND: Physical activity, calcium intake, coffee, alcohol and tobacco consumption can influence OP risk. These factors can be modifiable and, in some cases, their control may contribute for the OP prevention. OBJECTIVES: To identify and to evaluate associations between modifiable risk or protective factors of OP, age and sex in Portuguese healthy subjects. To assess the knowledge about osteoporosis in the studied population stratified by age and sex. METHODS: Cross-sectional study of randomly selected healthy subjects aged 18 to 29 years or more than 50 years. Information was obtained on demographic, clinical, lifestyle and behavioural characteristics using a standard protocol. Alcohol and tobacco consumption, calcium intake, physical activity and knowledge about osteoporosis were quantified. RESULTS: 301 subjects, 199 females and 102 males were evaluated. They have been separated in four groups stratified by sex and age. All the individuals presented calcium intake below the recommended levels and, except for the group of young males, physical activity was very low. Tobacco consumption was higher in the young female group and had been initiated earlier. Alcohol consumption was higher in male individuals with more than 49 years, being wine the predominant drink, while younger preferred beer. Women older than 49 years presented reduced calcium intake and physical activity. DISCUSSION: Risk factors for OP have been identified in age groups prone to develop OP The differences found in the evaluated parameters between age and sex groups must be considered in campaigns for OP prevention, promoting calcium intake, physical activity and the fight against tobacco consumption. PMID- 17334046 TI - [Stroke as the dramatic presentation of infectious endocarditis: the importance of the clinical history]. AB - The authors describe a case of infective subacute endocarditis due to Streptococcus mitis in a 72 year-old woman with systemic complaints and joint symptoms, that had started 4 months before, diagnosed as a polymyalgia rheumatica, who suddenly presented with aphasia and hemiplegia. The delay in the diagnosis might be justified by the disregard of some details in the clinical history owe to the anxious/depressive personality of the patient. The devastating evolution of this case report illustrates that in patients with an inflammatory syndrome and cardiac murmur clinicians should be highly alert for the hypothesis of an infective subacute endocarditis. Ischemic stroke is a dramatic and rare presentation form of the disease. A detailed physical examination should be the first clinical approach to a patient with the diagnostic hypothesis of polymyalgia rheumatica. PMID- 17334047 TI - [Erosive enteropathy in a patient with polyarthritis]. AB - Anaemia is a common clinical feature in patients with rheumatoid arthritis and the coexistence of blood loss may not show an obvious iron deficiency anaemia. The cause may be a cancer or other reason for gastrointestinal bleeding that could be underestimated for being explained as associated with the chronic rheumatic disease. Although less described than gastroduodenal lesions, small bowel damage of non-steroidal anti-inflammatory drugs, used in the treatment of rheumatic diseases, are more common than previously thought. The authors describe a clinical case paradigmatic of the difficulties that may appear in the approach of anaemia in a patient with a chronic rheumatic disease and discuss some features of intestinal toxicity of nonsteroidal anti-inflammatory drugs. PMID- 17334048 TI - [Nail patella syndrome]. PMID- 17334049 TI - A strategy for describing the biosphere at candidate sites for repositories of nuclear waste: linking ecosystem and landscape modeling. AB - To provide information necessary for a license application for a deep repository for spent nuclear fuel, the Swedish Nuclear Fuel and Waste Management Co. has started site investigations at two sites in Sweden. In this paper, we present a strategy to integrate site-specific ecosystem data into spatially explicit models needed for safety assessment studies and the environmental impact assessment. The site-specific description of ecosystems is developed by building discipline specific models from primary data and by identifying interactions and stocks and flows of matter among functional units at the sites. The conceptual model is a helpful initial tool for defining properties needed to quantify system processes, which may reveal new interfaces between disciplines, providing a variety of new opportunities to enhance the understanding of the linkages between ecosystem characteristics and the functional properties of landscapes. This type of integrated ecosystem-landscape characterization model has an important role in forming the implementation of a safety assessment for a deep repository. PMID- 17334050 TI - Analysis of water flow paths: methodology and example calculations for a potential geological repository in Sweden. AB - Safety assessment related to the siting of a geological repository for spent nuclear fuel deep in the bedrock requires identification of potential flow paths and the associated travel times for radionuclides originating at repository depth. Using the Laxemar candidate site in Sweden as a case study, this paper describes modeling methodology, data integration, and the resulting water flow models, focusing on the Quaternary deposits and the upper 150 m of the bedrock. Example simulations identify flow paths to groundwater discharge areas and flow paths in the surface system. The majority of the simulated groundwater flow paths end up in the main surface waters and along the coastline, even though the particles used to trace the flow paths are introduced with a uniform spatial distribution at a relatively shallow depth. The calculated groundwater travel time, determining the time available for decay and retention of radionuclides, is on average longer to the coastal bays than to other biosphere objects at the site. Further, it is demonstrated how GIS-based modeling can be used to limit the number of surface flow paths that need to be characterized for safety assessment. Based on the results, the paper discusses an approach for coupling the present models to a model for groundwater flow in the deep bedrock. PMID- 17334051 TI - Modeling water exchange and contaminant transport through a Baltic coastal region. AB - The water exchange of the Baltic coastal zone is characterized by its seasonally varying regimes. In the safety assessment of a potential repository for spent nuclear fuel, it is important to assess the consequences of a hypothetical leak of radionuclides through the seabed into a waterborne transport phase. In particular, estimates of the associated residence times in the near-shore coastal zone are of interest. There are several methods to quantify such measures, of which three are presented here. Using the coastal location of Forsmark (Sweden) as an example, methods based on passive tracers, particle trajectories, and the average age distribution of exogeneous water parcels are compared for a representative one-year cycle. Tracer-based methods can simulate diffusivity more realistically than the other methods. Trajectory-based methods can handle Lagrangian dispersion processes due to advection but neglect diffusion on the sub grid scale. The method based on the concept of average age (AvA) of exogeneous water can include all such sources simultaneously not only boundary water bodies but also various (fresh)-water discharges. Due to the inclusion of sub-grid diffusion this method gives a smoother measure of the water renewal. It is shown that backward in time trajectories and AvA-times are basically equipollent methods, yielding correlated results within the limits set by the diffusivity. PMID- 17334052 TI - Modeling carbon turnover in five terrestrial ecosystems in the boreal zone using multiple criteria of acceptance. AB - Estimates of carbon fluxes and turnover in ecosystems are key elements in the understanding of climate change and in predicting the accumulation of trace elements in the biosphere. In this paper we present estimates of carbon fluxes and turnover times for five terrestrial ecosystems using a modeling approach. Multiple criteria of acceptance were used to parameterize the model, thus incorporating large amounts of multi-faceted empirical data in the simulations in a standardized manner. Mean turnover times of carbon were found to be rather similar between systems with a few exceptions, even though the size of both the pools and the fluxes varied substantially. Depending on the route of the carbon through the ecosystem, turnover times varied from less than one year to more than one hundred, which may be of importance when considering trace element transport and retention. The parameterization method was useful both in the estimation of unknown parameters, and to identify variability in carbon turnover in the selected ecosystems. PMID- 17334053 TI - Carbon budgets for catchments across a managed landscape mosaic in southeast Sweden: contributing to the safety assessment of a nuclear waste repository. AB - Ecosystem budgets of matter contribute to the assessment of transport and accumulation of bioavailable contaminants in a landscape, since flows of matter and energy ultimately determine the rates at which contaminants will be partitioned in the environment. This study compares ecosystem properties, such as net primary production (NPP), sequestration of matter and fluxes to food sources for humans, which are of potential interest to describe fluxes and accumulation of bioavailable radionuclides in 14 catchments within a larger catchment area in southeast Sweden. The carbon budgets, used as a proxy for organic matter, are mainly based on local estimates of pools and fluxes, which have been distributed across a landscape mosaic of different vegetation types and management regimes using a geographical information system (GIS). NPP varied by a factor close to two (432 - 709 g x Cx m(-2)x y(-1)), while net ecosystem production ranged between -124 and 159 gx C x m(-2) x y (-1) for the different catchments. Carbon sequestration mainly occurred in the vegetation while the soil organic carbon pool was mainly a source of carbon. Large herbivores consumed on average 4.5 % of the above-ground green tissue production. When arable land was present in the catchment, the flux of carbon to humans was highest from crops and, in decreasing order, milk and beef, followed by the flux from hunting and berry/fungus picking. The results can be used to estimate the potential assimilation of radionuclides in vegetation and the potential exposure to humans of bioavailable radionuclides. PMID- 17334054 TI - A carbon budget of a small humic lake: an example of the importance of lakes for organic matter cycling in boreal catchments. AB - Lakes play an important role in the cycling of organic matter in the boreal landscape, due to the frequently high extent of bacterial respiration and the efficient burial of organic carbon in sediments. Based on a mass balance approach, we calculated a carbon budget for a small humic Swedish lake in the vicinity of a potential final repository for radioactive waste in Sweden, in order to assess its potential impact on the environmental fate of radionuclides associated with organic matter. We found that the lake is a net heterotrophic ecosystem, subsidized by organic carbon inputs from the catchment and from emergent macrophyte production. The largest sink of organic carbon is respiration by aquatic bacteria and subsequent emission of carbon.dioxide to the atmosphere. Although the annual burial of organic carbon in the sediment is a comparatively small sink, it results in the build-up of the largest carbon pool in the lake. Hence, lakes may simultaneously disperse and accumulate organic-associated radionuclides leaking from a final repository. PMID- 17334055 TI - Comparison of a mass balance and an ecosystem model approach when evaluating the carbon cycling in a lake ecosystem. AB - Carbon budgets are frequently used in order to understand the pathways of organic matter-in ecosystems, and they also have an important function in the risk assessment of harmful substances. We compared two approaches, mass balance calculations and an ecosystem budget, to describe carbon processing in a shallow, oligotrophic hardwater lake. Both approaches come to the same main conclusion, namely that the lake is a net autotrophic ecosystem, in spite of its high dissolved organic carbon and low total phosphorus concentrations. However, there were several differences between the carbon budgets, e.g. in the rate of sedimentation and the air-water flux of CO2. The largest uncertainty in the mass balance is the contribution of emergent macrophytes to the carbon cycling of the lake, while the ecosystem budget is very sensitive towards the choice of conversion factors and literature values. While the mass balance calculations produced more robust results, the ecosystem budget gave valuable insights into the pathways of organic matter transfer in the ecosystem. We recommend that when using an ecosystem budget for the risk assessment of harmful substances, mass balance calculations should be performed in parallel in order to increase the robustness of the conclusions. PMID- 17334056 TI - Marine ecosystem modeling beyond the box: using GIS to study carbon fluxes in a coastal ecosystem. AB - Studies of carbon fluxes in marine ecosystems are often done by using box model approaches with basin size boxes, or highly resolved 3D models, and an emphasis on the pelagic component of the ecosystem. Those approaches work well in the ocean proper, but can give rise to considerable problems when applied to coastal systems, because of the scale of certain ecological niches and the fact that benthic organisms are the dominant functional group of the ecosystem. In addition, 3D models require an extensive modeling effort. In this project, an intermediate approach based on a high resolution (20x20 m) GIS data-grid has been developed for the coastal ecosystem in the Laxemar area (Baltic Sea, Sweden) based on a number of different site investigations. The model has been developed in the context of a safety assessment project for a proposed nuclear waste repository, in which the fate of hypothetically released radionuclides from the planned repository is estimated. The assessment project requires not only a good understanding of the ecosystem dynamics at the site, but also quantification of stocks and flows of matter in the system. The data-grid was then used to set up a carbon budget describing the spatial distribution of biomass, primary production, net ecosystem production and thus where carbon sinks and sources are located in the area. From these results, it was clear that there was a large variation in ecosystem characteristics within the basins and, on a larger scale, that the inner areas are net producing and the outer areas net respiring, even in shallow phytobenthic communities. Benthic processes had a similar or larger influence on carbon fluxes as advective processes in inner areas, whereas the opposite appears to be true in the outer basins. As many radionuclides are expected to follow the pathways of organic matter in the environment, these findings enhance our abilities to realistically describe and predict their fate in the ecosystem. PMID- 17334057 TI - Pools and fluxes of organic matter in a boreal landscape: implications for a safety assessment of a repository for nuclear waste. AB - To provide information necessary for a license application for a deep repository for spent nuclear fuel, the Swedish Nuclear Fuel and Waste Management Co is carrying out site investigations, including extensive studies of different parts of the surface ecosystems, at two sites in Sweden. Here we use the output from detailed modeling of the carbon dynamics in the terrestrial, limnic and marine ecosystems to describe and compare major pools and fluxes of organic matter in the Simpevarp area, situated on the southeast coast of Sweden. In this study, organic carbon is used as a proxy for radionuclides incorporated into organic matter. The results show that the largest incorporation of carbon into living tissue occurs in terrestrial catchments. Carbon is accumulated in soil or sediments in all ecosystems, but the carbon pool reaches the highest values in shallow near-land marine basins. The marine basins, especially the outer basins, are dominated by large horizontal water fluxes that transport carbon and any associated contaminants into the Baltic Sea. The results suggest that the near land shallow marine basins have to be regarded as focal points for accumulation of radionuclides in the Simpevarp area, as they receive a comparatively large amount of carbon as discharge from terrestrial catchments, having a high NPP and a high detrital accumulation in sediments. These focal points may constitute a potential risk for exposure to humans in a future landscape as, due to post glacial land uplift, previous accumulation bottoms are likely to be used for future agricultural purposes. PMID- 17334058 TI - Rural landscape, production and human consumption: past, present and future. AB - Production and consumption of food and in a rural area over the last 400 years were reconstructed for a parish in south east Sweden. This was based on a number of different data sources, including historical maps and official demographic and agricultural statistics. Changes in population (and thus consumption) and the production from arable land and livestock were calculated and used to provide an estimate of the area's supply and demand over time, and of the historical sustainability of the area. Overall food productivity was remarkably constant over time, at approximately 0.04 kgC m(-2) y(-1), despite recent changes in population size and the area of cultivated land. The empirical results from the past and the present, together with the future land changes due to shoreline displacement were used to predict the situation in the future. These final estimates can be used in the assessment of risk for exposure to contaminated food for the future population in the area. PMID- 17334059 TI - Modeling the long-term transport and accumulation of radionuclides in the landscape for derivation of dose conversion factors. AB - To evaluate the radiological impact of potential releases to the biosphere from a geological repository for spent nuclear fuel, it is necessary to assess the long term dynamics of the distribution of radionuclides in the environment. In this paper, we propose an approach for making prognoses of the distribution and fluxes of radionuclides released from the geosphere, in discharges of contaminated groundwater, to an evolving landscape. The biosphere changes during the temperate part (spanning approximately 20,000 years) of an interglacial period are handled by building biosphere models for the projected succession of situations. Radionuclide transport in the landscape is modeled dynamically with a series of interconnected radioecological models of those ecosystem types (sea, lake, running water, mire, agricultural land and forest) that occur at present, and are projected to occur in the future, in a candidate area for a geological repository in Sweden. The transformation between ecosystems is modeled as discrete events occurring every thousand years by substituting one model by another. Examples of predictions of the radionuclide distribution in the landscape are presented for several scenarios with discharge locations varying in time and space. The article also outlines an approach for estimating the exposure of man resulting from all possible reasonable uses of a potentially contaminated landscape, which was used for derivation of Landscape Dose Factors. PMID- 17334060 TI - [Prophylactic effect of fosfomycin on postoperative infection in gastroenterological surgery]. AB - Fosfomycin (FOM), a drug with unique mechanism of action against bacteria, was prospectively compared with cefmetazole (CMZ) and flomoxef (FMOX) to assess its effectiveness in preventing postoperative infections after upper gastroenterological and hepatobiliary surgery. FOM (2g/dose), CMZ (1 g/dose), or FMOX (lg/dose) was infused intravenously 2-3 times daily for basically 4 days including the day of surgery in order to examine whether or not infections would develop after surgery. According to the analysis results of 162 cases, efficacy in preventing infection was 86.8% for FOM, 73.1% for CMZ and 83.3% for FMOX, showing no significant differences among the 3 groups. Thus FOM was considered as efficacious as CMZ or FMOX in prophylaxis against postoperative infections. There were no adverse reactions in the FOM or CMZ group, but 3 cases of adverse reactions occurred in the FMOX group. Based on the above results, the usefulness of FOM for prophylaxis against postoperative infections has been confirmed. At present, the first- and second-generation cephems are most frequently used for prophylaxis against postoperative infections. In order to prevent an increase of resistant strains due to inappropriate use of these drugs, FOM, having no cross resistance with currently used drugs, is a promising candidate for prophylaxis against postoperative infections. PMID- 17334062 TI - [Bilophila wadsworthia isolated from surgical specimens]. AB - Bilophila wadsworthia is a recently recognized nonspore-forming anaerobic Gram negative rod and is reported to be associated with various surgical infections. In the present study, the isolation rate of B. wadsworthia from surgical specimens and its antimicrobial susceptibilities were examined. Last 5 years, B. wadsworthia was isolated from 46 (5.2%) out of 884 specimens from the surgical abdominal infections. B. wadsworthia was most frequently isolated from secondary peritonitis such as perforated peritonitis, followed by postoperative peritonitis. There is no case of single isolation of B. wadsworthia. The rate of mixed infection with Bacteroides spp. (24.8%) was highest, followed by Escherichia coli (11.6%) and Enterococcus spp. (10.1%). Although B. wadsworthia was highly resistant to many beta-lactam antibiotics, clindamycin showed strongest activities with MIC90 of 1 microg/mL, followed by minocycline and ciprofloxacin with 4micro g/mL, and levofloxacin with 8 microg/mL, respectively. PMID- 17334063 TI - [Administration method of meropenem on the basis of PK/PD (pharmacokinetics/pharmacodynamics) in consideration of renal function]. AB - The reasonable data on the basis of a PK/PD theory in clinical practice would be provided by the analysis in consideration of renal function because the excretion of meropenem mainly occurs from kidney. We carried out the simulation with pharmacokinetics of meropenem in consideration of renal function, and investigated whether renal function would affect Time above MIC (T>MIC). The % T>MICs were 18.9%, 35.0%, 49.4%, 61.1% in serum creatinine level 0.5, 1.0, 1.5, and 2.0 mg/dL, respectively, when MIC of causative organism was assumed to 4microg/mL. Furthermore, we investigated the association between renal function and clinical efficacy in three patients with peritonitis, who received meropenem. We conclude that the simulation in consideration of renal function would be useful in PK/PD-based analysis, and would give the clinically useful data in clinical practices. PMID- 17334061 TI - [In-vitro susceptibilites to levofloxacin and various antibacterial agents of 18,639 clinical isolates obtained from 77 centers in 2004]. AB - A total of 18,639 clinical isolates in 19 species collected from 77 centers during 2004 in Japan were tested for their susceptibility to fluoroquinolones (FQs) and other selected antibiotics. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae showed a high susceptible rate against FQs. The isolation rate of beta lactamase non-producing ampicillin-resistant H. influenzae was approximately three times as large as those of western countries. Most strains of Enterobacteriaceae were also susceptible to FQs. The resistance rate of Escherichia coli against FQs has however been rapidly increasing so far as we surveyed since 1994. The FQs-resistant rate in methicillin-resistant Staphylococcus aureus (MRSA) showed approximately 90% except for 36%. of sitafloxacin while FQs-resistant rate in methicillin-susceptible S. aureus (MSSA) was around 5%. The FQs-resistant rate of methicillin-resistant coagulase negative Staphylococci (MRCNS) was also higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), however, it was lower than that of MRSA. In Pseudomonas aeruginosa clinical isolates, 32-34% from UTI and 15-19% of from RTI was resistant to FQs. Acinetobacter spp. showed a high susceptibility to FQs. Although FQs-resistant Neisseria gonorrhoeae have not been increased in western countries, it is remarkably high in Japan. In this survey, isolates of approximately 85% was resistant to FQs. PMID- 17334064 TI - [Evaluation of efficacy of oral quinolone against Streptococcus pneumoniae AND Haemophilus influenzae with the use of Monte Carlo simulation]. AB - We investigated the efficacies of various administration methods for levofloxacin (LVFX) and tosufloxacin (TFLX) against 161 isolates of Streptococcus pneumoniae and 309 isolates of Haemophilus influenzae isolated in Gifu prefecture, using Monte Carlo simulation. The pharmacokinetic parameters of the fluoroquinolones were calculated from changes in blood concentration in healthy adults. Monte Carlo simulation was performed for 1,000 times to determine the AUC/MIC target attainment rates for various administration methods for fluoroquinolones (LVFX: 100 mgx3, 200 mgx2, 500 mgx 1, TFLX: 150 mgx3, 300 mgx2) with Crystal Ball 7. For S. pneumoniae, target attainment rates ofAUC/MIC; 30 were 47.18%, 75.54%, 89.16%, 93.63% and 98.63% for LVFX 100mgx3, LVFX 200mgx2, LVFX 500mgxl, TFLX 150mgx3 and TFLX 300mgx2, respectively. For H. influenzae, target attainment rates of AUC/MIC; 125 were 99.20%, 99.05%, 99.54%, 99.66% and 100% for LVFX 100mgx3, LVFX 200mgx2, LVFX 500mgxl, TFLX 150mgx3 and TFLX 300mgx2, respectively. These results suggest that administration methods might have a large impact on the efficacy of treatment with oral fluoroquinolones, and to determine administration method based on PK/PD would be important in clinical practices. PMID- 17334065 TI - [Expression of core binding factor a1, bone morphogenetic proteins and osteopontin in the developing periodontal tissues of mice]. AB - OBJECTIVE: To study the expression and interaction of core binding factor a1 (Cbfa1), bone morphogenetic proteins (BMPs) and osteopontin (OPN) in the developing periodontal tissues of mice. METHODS: A mice developing periodontal tissues study model was created histologically by 5-27 day postnatal BALB/c mice, then the immunohistochemical localization of Cbfa1, BMPs and OPN in different developing stages were undertaken. RESULTS: In early stage of postnatal mice periodontal tissues development, only BMPs expressed in dental follicle cells, though the signal was weak. When root was forming, all of them were expressed in periodontal ligament cells and cementoblasts, while only OPN in acellular cementum, cellular cementum and the surface of alveolar bone, Cbfa1 only in cellular cementum and BMPs was seen in neither acellular cementum nor cellular cementum. CONCLUSION: Cbfa1, BMPs and OPN all involve in the development of periodontal tissues, while OPN is crucial for cementum. PMID- 17334067 TI - [Expression of cyclin D1 and its inhibitors and hTERT in ameloblastoma]. AB - OBJECTIVE: To investigate the expression of human telomerase reverse transcripase (hTERT), cyclin D1 mRNA, p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein in human ameloblastoma (ABs). METHODS: The expression of hTERT, cyclin D1, p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein in 54 cases of human ABs were detected by in situ hybridization or immunohistochemistry. RESULTS: The positive cases of hTERT mRNA, cyclin D1 mRNA was 51, 23, respectively. The positive cases of p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein was 17, 12, 9. Comparing with recurred and transformed malignantly, the expression of hTERT mRNA, cyclin D1 mRNA increased, and the expression of p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein decreased or lost. The expression of hTERT mRNA and pl6(INK4), p21(WAF1) mRNA and p27(KIP1) protein in ABs had middle to high negative relation (r(k) = -0.587, r(k) = 0.652, r(k) = -0.783, P < 0.001). CONCLUSION: The hTERT mRNA expression in ABs is related to the reguation of pl6(INK4), p21(WAF1) mRNA and p27(KIP1) protein. PMID- 17334066 TI - [Compare the effect of lipo- and normal prepared Sodium Morrhuate on ECV-304 cell line]. AB - OBJECTIVE: To compare the effect of Sodium Morrhuate on ECV-304 between its lipo- and normal preparation. METHODS: The ECV-304 cell line was supplemented with Sodium Morrhuate and lipo-Sodium Morrhuate in order, and the result on morphology (microscope, Giemsa Staining and electron microscope), cell activity (MTT), and flow cytometer between the two preparation were compared. RESULTS: In normal preparation group, cell's edema occurred. Chromatin was like catkins. Tumefaction and degeneration of mitochondrion and endoplasmic reticulum appeared. In lipo Sodium Morrhuate group, the membrane was creased and processus appeared. Chromatin aggregates to the membrane of nucleus was like crescent, and then broken. The apoptotic body was formed. MTT changes showed that the curve of the normal preparation group was steep and the change time was short relatively, which cues the vital cells decreased sharply. The curve of lipo-Sodium Morrhuate group was gentle and the change time was long relatively, which cues the vital cells decreased slowly. The flow cytometer showed that typical apoptosis peak appeared. CONCLUSION: The normal preparation group shows an acute toxic effect on ECV-304 cell line, which result in a necrosis course, while lipo-Sodium Morrhuate shows a gradual releasing process, which may indicate a apoptosis course. PMID- 17334069 TI - [Influence of fiber framework design on stress distribution in posterior glass fiber reinforced composite resin-bonded fixed partial dentures]. AB - OBJECTIVE: To compare the difference of stress distribution among models with different fiber frameworks. METHODS: Four models were generated in Marc 2003 software. Four types of loads simulating normal mastication were selected. The stress within models was calculated, and output by means of graph and data. RESULTS: There was stress concentration around connectors and retainers near connectors under cusp -fossa load, occlusal even load, and lateral load. When dentures were reinforced with fiber framework, area of stress concentration and principal stress max could decrease in comparison with pure composite resin bonded fixed partial denture. Under buccal-lingual load, there was another stress concentration around central fossa beside above two stress concentration areas. Only modified fiber framework constructed with both mesial-distal and lingual buccal directional glass fiber could markedly reduce principal stress under buccal-lingual cusp loads. CONCLUSION: Under 4 types of loads simulating normal mastication, three critical regions were disclosed at the area of retainers adjacent connectors, connectors and occlusal central fossa and fissures. Only modified fiber framework constructed with both mesial-distal and lingual-buccal directional glass fiber could markedly reduce stress concentration under buccal lingual cusp loads. PMID- 17334068 TI - [Structural characteristics of laser-welded cast pure titanium joints by different gap distance]. AB - OBJECTIVE: To measure the microstructure of laser-welded cast pure titanium by different gap distance. METHODS: Forty specimens were sectioned and welded at four gaps (0.00 mm, 0.25 mm, 0.50 mm and 1.00 mm). Took microhardness test and metallographic examination of welded zone surface. RESULTS: There were no difference in microhardness value and metallographic observation between welded specimens. The width of heat-effected zone was different. The smaller grains and needle-like alphamartensitic structure were found in the heat-affected zone. CONCLUSION: The effects of the joint gap were not significant. PMID- 17334070 TI - [Study on different thickness and chromatics of various opaques]. AB - OBJECTIVE: To study the effect existed in the course of adopting different thickness and chromatics of various opaques so that a good methods can be provided for clinical care in prosthodontics. METHODS: A model of using the thin plastic paper to control the ceramic thickness was applied in this test. The data of chromaticity was measured by TC-PIIG auto color difference meter and its results was processed by computer. RESULTS: The value of brightness had an uptrend increase with augment of opaques thickness. Metal base color was opaqued and the basic hue was set. A lower and unstable value, besides a relative stable Y, was measured with the uncompleted opaquing. A stability of hue had been gradually concentrated within a certain range accompanying with the increase of opaquing ceramic thickness. A concentrated hue in the second thickness was found in CARAT ceramic which had high ability of opaque and had a stable hue of ceramic in comparison with other opaques. Among those changes, CARAT's brightness showed a minimal change; a gradual stability of chromatics was presented and was limited with-in a certain range though the augment of opaques. CONCLUSION: The metal color in base could be completely opaqued while opaques thickness reaches a certain range. CARAT is the materials of minimal thickness and has relatively strong capacity for opaques. PMID- 17334071 TI - [Optimized thread pitch design and stress analysis of the cylinder screwed dental implant]. AB - OBJECTIVE: To determine the optimal thread pitch for an experimental cylinder implant in Ansys Work-bench Design Xplorer environment. METHODS: Finite element models of segment jaw bone with a V-shaped thread implant were created. The thread pitch (P) was set from 0.5 mm to 1.6 mm. The maximum Equivalent stresses (EQV stresses) in jaw bone and in implant were evaluated. RESULTS: Under axial load, the amplification of maximum EQV stresses in cortical bone, cancellous bone and implant were 7.1%, 123.4% and 28.7% respectively. Under bucco-lingual load, the amplification of maximum EQV stresses in cortical bone, cancellous bone and implant were 2.8%, 28.8% and 14.9% respectively. When P exceeded 0.8 mm, the response curve curvature of maximum EQV stresses in jaw bone and in implant to P was ranged from -1 to 1. CONCLUSION: Stresses in cancellous bone are more sensitive to thread pitch than in cortical bone. Stresses in jaw bone under axial load are easier affected by thread pitch than under bucco-lingual load. Thread pitch plays a greater role in protecting dental implant under axial load than under bucco-lingual load. Thread pitch exceed 0.8 mm should be the optimal design in a cylinder implant, but oversized pitch should be avoided too. PMID- 17334072 TI - [Measurement and comparison of the spectral transmittance of cerinate porcelain and human enamel]. AB - OBJECTIVE: To measure the spectral transmittance of Cerinate porcelain veneer and enamel in different color and different thickness. METHODS: Samples of Cerinate porcelain veneers were prepared in different thickness (0.50 mm, 0.75 mm, 1.00 mm) and different Vita shade (A1, A2, A3). Enamel samples in shade A2 were made with three thickness (0.50 mm, 0.75 mm, 1.00 mm). A spectrophotometer with spectra range (380-800 nm) was employed to measure the spectral transmittance. RESULTS: Spectral transmittance decreased with the increasing in the thickness of specimens and decreasing in the color darkness. The transmittance of Cerinate porcelain veneer material and enamel in the same color and same thickness hadn't significant difference. CONCLUSION: The key factor to spectral transmittance of porcelain veneer materials is veneer's thickness, and the color of the materials has also some influence on it. Cerinate porcelain veneers can properly recover the transparency of teeth. PMID- 17334073 TI - [Measuration of instantly galvanic current magnitude among dental common restorative alloys]. AB - OBJECTIVE: To measure the magnitude of galvanic currents produced by different occluding metallic contact. METHODS: The circuits of instantly different metallic contact were simulated in artificial saliva, and electrical potential of every couple and 15 currents of instant contact were then measured. After 8 hours' soaking, 15 currents were obtained in addition. RESULTS: Galvanic currents variation produced hy intermittently metallic contact was ruleless. During early soaking, gold/titanium, gold/high zinc-containing amalgam and low/high zinc containing amalgam exhibited much higher current, and there was significant difference on currents between titanium/high zinc-containing amalgam and other couples (P < 0.05). There was also significant difference on currents between titanium/high zinc containing amalgam, titanium/low zinc-containing amalgam and gold/titanium, gold/low zinc-containing amalgam and gold/high zinc-containing amalgam after 8 hours' soaking (P < 0.05). In contrast with currents produced by couples before and after 8 hours' soaking, only the currents produced by gold/high zinc-containing amalgam proved to be no significant of difference (P > 0.05), while the currents produced by gold/low zinc-containing amalgam and titanium/high zinc-containing amalgam increased. Potential of high zinc containing amalgam was more negative than other alloys, and it was always under anodic behavior during the experiment corrupted acceleratedly. CONCLUSION: Dentists can't ignore the case that the patient feels normal at the beginning of wearing different occluding metallic restorations. Either of gold/ titatium, gold/high zinc-containing amalgam and low/high zinc-containing amalgam appearing in oral will do harm to the patients' health. Neither of gold/low zinc-containing amalgam nor titanium/high zinc-containing amalgam can coexist in oral. Zinc-free or low zinc-containing amalgam should be selected instead of high zinc-containing amalgam. PMID- 17334074 TI - [Condylar morphology with different vertical facial types of skeletal III malocclusions in mixed dentition]. AB - OBJECTIVE: To study the difference of condylar morphology with different vertical facial types of skeletal III malocclusions in mixed dentition. METHODS: Orthopantomograms of 60 children with different vertical facial types were retrospectively investigated by computerized cephalometric analysis. Condylar morphology was compared among different vertical facial type groups. RESULTS: There was statistical difference in upper condylar height among groups, the height increased from high angle group, average angle group to low angle group. There was no significant difference in ramus height in the groups. There was statistical difference in the upper condylar height to the ramus height radio in different vertical facial type groups (P < 0.01). The ratio increased from high angle group, average angle group to low angle group. There was no significant difference in the condylar height to the condylar neck width ratio in the groups. CONCLUSION: In children of skeletal III malocclusions in mixed dentition with different vertical facial types, there are statistical differences in condylar morphology, which might be due to different growth of mandibular. PMID- 17334075 TI - [Association of the progress of chronic periodontitis with interleukin-1B-511 genetic polymorphisms]. AB - OBJECTIVE: To study the natural progress of different degree chronic periodontitis and its association with IL-1B-511 genetic polymorphisms. METHODS; 100 subjects with chronic periodontitis were selected and examined at baselined and in the 6 month and in 1 year on attatchment loss at 6 sites of each tooth. DNA samples were obtained with buccal swabbing technique and were further analyzed for IL-1B-511 genotype polymorphisms using PCR-RFLP-based method in all subjects. RESULTS: The mean AL increases were 1.43 mm within 1 year. Among 100 subjects, 16 patients with moderate progression (0 mm < AL increase/a year < or = 1.0 mm), 84 patients with rapid progression of periodontal disease (AL increase/ a year > 1.0 mm). There was no significant difference for the distribution and frequency of IL-1B-511 genotype and alleles between the AL increase/ a year > 1.0 mm group and AL increase/a year < or = 1.0 mm group. The progression of periodontal disease (AL increase/a year > 1.0 mm group) was significantly higher in the non-severe chronic periodontitis group than in the severe group (P < 0.05). The percentage of molar was higher as far as the rapid-progress sites (AL increase > 2.0 mm both in the 6th and the 12th months examination) were concerned than that of premolar and anterior (P < 0.05). The number of progressed sites in the severe group was higher than the non-severe chronic periodontitis group (P < 0.05). CONCLUSION: The progress of chronic periodontits varies individually. No specific relationship was found between the progression of chronic periodontitis and IL-1 gene polymorphisms. PMID- 17334076 TI - [Study on the horizontal transmission of oral Streptococcus mutans in day-nursery children]. AB - OBJECTIVE: To analyze genotypic diversity of oral Streptococcus mutans (S. mutans) and find out horizontal transmission possibility of the microbe in day nursery children. METHODS: The plaque samples were scratched with sterilized toothpicks from teeth of 32 day-nursery children aged between 3 and 4, then cultured on MSB plates. Clones with representative S. mutans-like were subcultured and identified to species level biochemically. AP-PCR fingerprinting was performed to distinguish genotypic diversity of those isolates. Then S. mutans isolated from different children with very similar amplicon profiles were examined by chromosomal DNA fingerprinting analysis. RESULTS: S. mutans were isolated in oral cavities of 78.1% children, 100% in caries and 69.6% in caries free children. A total of 57 genotypes were identified by AP-PCR. More than one amplitypes were identified in 88% of the 25 children with S. mutans colonization. Two pair of children shared common genotypic S. mutans. CONCLUSION: There is no evident relation between number of genotype detected and caries. The presence of matching genotypes of S. mutans among day-nursery children suggests the horizontal transmission may exist. PMID- 17334077 TI - [168 cases of free flap transplantation with double vein anastomoses for reconstruction of head and neck defects]. AB - OBJECTIVE: To evaluate the reliability and effectiveness of free flap transfer with double vein anastomosis for reconstruction of head and neck defects. METHODS: One hundred and sixty-eight cases of free flap transfers with double vein anastomosis for head and neck reconstruction from September 1999 to April 2003 were reviewed. There were 92 males and 76 females. The age range was 11 to 79 years old, with the average of 44.6 years old. Data concerning the operation included site, stage and histology of tumor, defect description, design of free flap, recipient vessel free flap survival and complications. RESULTS: Among 168 free flaps, there were 126 free fibula flaps, 32 radial forearm flaps, 7 rectus abdominis flaps, one scapular flap, one jejunal flap, and one anterolateral thigh flap. The overall success rate of free flap was 99.4%. One fibula flap was lost because of arterial thrombosis. No venous thrombosis occurred in this group. CONCLUSION: Free flap transfer with double vein anantomosis for head and neck reconstruction improves the outflow of free flap, reduces the venous thrombosis rate, and ensures a high success rate of free flaps. PMID- 17334078 TI - [Relationship between transforming growth factor-alpha gene polymorphism and non syndromic cleft lip with cleft palate]. AB - OBJECTIVE: To study the association of TGF-alpha gene polymorphism and non syndromic cleft lip with cleft palate in Shandong province. METHODS: Polymerase chain reaction combined with restrict enzyme digestion was used to detect the target gene variation in 98 patients with non-syndromic cleft lip with cleft palate and 101 healthy controls. RESULTS: The C2 allele frequency in patients with non-syndromic cleft lip with cleft palate was significantly higher than that in healthy controls. The genotype frequency in patients with positive family history was significantly higher than that without positive family history. CONCLUSION: TGF-alpha gene polymorphism is closely associated with non-syndromic cleft lip with cleft palate in Shandong, especially in patients with positive family history. PMID- 17334079 TI - [Effects of post length on horizontal load of post-core system]. AB - OBJECTIVE: To access the effects of post length on horizontal load of cast post and core crown. METHODS: 120 simulated roots made of polymethylmethacrylate were divided into 15 groups according to different mechanical fulcrum and length of post, made the wax pattern of post-core, casted and cemented the post-core. After saline soak, loaded these specimens on the Instron-4302 by the speed of 1 mm/min and recorded the maximum force of load. RESULTS: The means of fracture resistance Wp11 of 7.0 mm, 7.5 mm, 8.0 mm, 8.5 mm, 9.0 mm were (94.24 +/- 12.47) N, (129.76 +/- 19.89) N, (195.98 +/- 1 2.46) N, (208.88 +/- 24.37) N, (225.67 +/- 53.07) N and the means of dangerous stress (sigma degrees 11 were 65.12 N, 93.07 N, 145.84 N, 161.58 N, 181.49 N; the means of fair stress [sigma11] were 39.41 MPa, 56.34 MPa, 88.34 MPa, 97.86 MPa, 109.94 MPa. It showed that the horizontal load of post core crown system increased gradually with the increasing of the post length. It appeared the linear regression between the length of the post and fracture resistance and physiologic load. CONCLUSION: The increasing of the post length can increase the horizontal load of post-core crown system. During the pulp preparation of post-core system, the post length should be added as much as possible. PMID- 17334080 TI - [Sequencing and bioinformatical analysis of virulent strain-specific DNA fragments from Streptococcus mutans]. AB - OBJECTIVE: To search the DNA sequences specific to virulent strain of Streptococcus mutans in the public database and explore new genes or new functions of already known genes from Streptococcus mutans of serotype c and suppose their functions. METHODS: Thirty-one DNA fragments unique to virulent strain of Streptococcus mutans were sequenced. The sequences of these presumptive virulence DNA fragments were subjected to search through software BLASTn and BLASTx in public database, and their putative biological functions were analyzed. RESULTS Two clones were picked repeatedly. The size of the remaining DNA fragments ranged from 113 bp to 776 bp. The average G+C content was 38.59%, similar to that of the gene-coding sequences in Streptococcus mutans strain UA159 whose genome sequences were just complete. Of the twenty-nine DNA fragments, five potentially represented new DNA fragments in Streptococcus mutans, thus registered and obtained their gene's accession number in GenBank. The remaining DNA fragments showed high homology to known genes of Streptococcus mutans strain UA159. Their predicted functions of these fragments were associated to bacterial signal transduction, transcriptional regulation, stress-damage repair, biochemical metabolism, outer membrane protein synthesis, adhesion on tooth surface and hypothetical proteins. CONCLUSION: The gene analysis, identification and functional forecasting were carried out through bioinformatics associated software and database to find out new genes and new functions of known genes, and to supply the groundwork for researches in gene functions. PMID- 17334081 TI - [Study of susceptibility of oral bacteria biofilm to traditional Chinese drug preventing caries]. AB - OBJECTIVE: Using MBEC-Assay to assay minimal biofilm eradication concentration (MBEC) of Galla Chinensis and Nidus Vespae to oral bacterial biofilm. To set up traditional Chinese medicine susceptibility pharmacodynamic empirical study methods of oral bacterial biofilm. METHODS: Cariogenic bacteria strains were selected (Streptococcus mutans ATCC 25175, Streptococcus sanguis ATCC 10556, Lactobacillus rhamnosus AC 413, Actinomyces naeslundii WVU 627) in this study. Extraction components of Galla Chinensis were GCE (aqueous extract), GCE-B (30% alcohol extract) and extraction components of Nidus Vespae were NVE1 (95% alcohol extract). (1) To observe oral bacterial biofilm formatiom in MBEC-Device at different time. (2) MBEC-HTP-Assay: The minimal inhibitory concentration (MIC) and minimal biofilm eradication concentration (MBEC) of GCE, GCE-B and NVE1 to oral bacteria strains were determined. RESULTS: Oral bacterial biofilm were readily formed on the lid of MBEC-Device under selected condition (observed by SEM). Oral cariogenic bacteria growing as plankton populations were sensitive to GCE, GCE-B and NVE1. To GCE, GCE-B and NVE1, oral cariogenic bacterial biofilm were 2-16 times less susceptible than growing plankton bacteria. GCE and GCE-B were the most effective medicine against oral cariogenic bacterial biofilm. NVE1 were effective in killing oral-bacterial biofilm at relatively high concentration. CONCLUSION: GCE and GCE-B were effective medicine against oral cariogenic bacterial biofilm. MBEC (minimal biofilm eradication concentration) can provide a relative accurate medicine concentration for clinical test. PMID- 17334082 TI - [Analysis of gene expression of fatty acid synthase in squamous cell carcinoma of the oral cavity by the method of real-time quantitative PCR]. AB - OBJECTIVE: To relatively quantify the gene expression of fatty acid synthase in squamous cell carcinoma, adjacent tissue, and some normal oral tissues by real time quantitative PCR. METHODS: The tissues were collected fresh from surgical specimens. The collected tissues were minced. Then the total RNA was extracted. The RNA was reversely transcripted into cDNA with random prime. And then the cDNA was amplified by real-time quantitative PCR to quantify the gene expression of FAS according to an internal control GAPDH. The difference of FAS gene expression was compared between squamous cell carcinoma, adjacent tissue, and some normal oral tissues. RESULTS: The expression of FAS of squamous cell carcinoma was notably higher than the other two (P < 0.001). CONCLUSION: Real-time quantitative PCR provides a method for monitoring the expression of fatty acid synthetic activity in squamous cell carcinoma, adjacent and normal tissues. PMID- 17334083 TI - [Surface modification of dental alumina ceramic with silica coating]. AB - OBJECTIVE: To make silica coating through sol-gel process, and to evaluate the wettability of dental alumina ceramic with or without coating. METHODS: Silica coating was prepared with colloidal silica sol on In-Ceram alumina ceramic surface which had been treated with air particle abrasion. Coating gel after heat treatment was observed with atomic force microscope (AFM), and was analyzed by infrared spectrum (IR) with gel without sintered as control. Contact angles of oleic acid to be finished, sandblasted and coated ceramic surface of were measured. RESULTS: AFM pictures showed that some parts of nano-particles in coating gel conglomerated after heat treatment. It can be seen from the IR picture that bending vibration absorption kurtosis of Si-OH also vanished after heat treatment. Among contact angles of three treated surface, the ones on polished surface were the biggest (P = 0.000, P = 0.000), and sandblasting+silica coating surface the smallest (P = 0.000, P = 0.003). CONCLUSION: Silica coating can be made with sol-gel process successfully. Heat treatment may reinforce Si-O Si net structure of coating gel. Wettability of dental alumina ceramic with silica coating is higher than with sandblasting and polishing. PMID- 17334084 TI - [The Japanese language and psychotherapy, with a particular focus on the handling of "contradictions"]. AB - Verbalization, a technique used in analytic psychotherapy, plays a variety of roles including "naming", "uncovering", "clarifying", "weaving a story", and "thinking about the story". When we apply this technique in Japanese, however, resistance to such verbalization is liable to occur. Japanese is often said to be an "ambiguous" language. However, the only reason the Japanese language sounds ambiguous is because Japanese people use it ambiguously. One of the reasons for Japanese people's psychology of placing importance on polysemy and ambiguity is that it is unreasonable to impose an artificially-coined word on another person, and try to make him or her "share it" or "understand it". As a term that opposes "words" in Japanese, there is "jo" (affect) or "kanjo" (emotion) ; and the so called non-verbal exchange that is emphasized in the Japanese language includes physical contact (such as touching) and interplay of the emotions. Structures that emphasize duality-such as "tatemae to honne," or what one says and what one really means, and "giri to ninjo," or duty and feeling-are internalized in the character of the Japanese people. This is reflected in daily context by the pattern of conflict that Japanese people share: namely, verbal versus nonverbal exchanges. In this paper, the author discusses how the contradictions and discrepancies seen in such exchanges originate from mother-child relationships, and proposes that therapeutic relations be used as an opportunity to deal with such contradictions and ambiguities. In particular, the author quotes from "Yuzuru (The Crane Wife)" and other Japanese folktales, and points out that, to deal with individual tragedies, like the heroine of "Yuzuru" who leaves her husband after he discovers her true nature, the therapist must recognize the existence of such contradictions in himself/herself. For example, contradictions such as a therapist being possibly ill despite appearing healthy, is liable to become a key target of patient scrutiny for testing the therapeutic objective. PMID- 17334085 TI - [Clinical features of patients with obsessive-compulsive disorder showing different pharmacological responses]. AB - BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharmacological treatment for obsessive-compulsive disorder (OCD), some OCD patients do not show improvement. Sometimes, the addition of a low-dose atypical antipsychotic, such as risperidone, or olanzapine, to ongoing SSRI treatment has been shown to be effective. However, there are patients who still show no response after trials with this augmentation therapy. In the present study, we examined the clinical features of OCD patients who showed different responses to pharmacological treatment. SUBJECTS AND METHOD: Fifty OCD patients were divided into three groups according to their pharmacological responses: responders to SSRI (group A: n= 25), responders to SSRI with an atypical antipsychotic (group B: n= 15), and non-responders to both SSRI and SSRI with an atypical antipsychotic (group C: n= 10). We examined the clinical features such as age, sex, age of onset, duration of illness, types of obsessive-compulsive symptoms, severity, improvement after treatment, insight into disease, depression, comorbidity, involving family members in compulsive or ritualistic behavior, and the level of social adaptation of each OCD group. RESULTS: Twenty five patients showed a good response to SSRI monotherapy, 15 showed a response to antipsychotic augmentation, and 10 were non-responders to both SSRI and SSRI with an atypical antipsychotic. Significantly lower insight levels were observed only in group B and higher depressive levels in group C. OCD patients who were refractory to SSRI monotherapy showed comorbidity at a significantly higher frequency. OCD patients in group A showed significantly greater improvement, and group B showed inferior social adaptation after treatment. There were no significant differences in age, sex, age of onset, duration of illness, severity, involving family members in compulsive or ritualistic behavior, and social adaptation before treatment in the three OCD groups. CONCLUSION: There were differences in the clinical features of OCD patients who showed different responses to pharmacological treatment. Our results suggest that OCD is clinically and biologically heterogeneous. It may be important to divide OCD patients into subgroups for future studies. PMID- 17334086 TI - [The day treatment model for schizophrenia in the decades of community care]. PMID- 17334087 TI - [Ultraviolet irradiation-mediated malignant melanoma induction with RET tyrosine kinase activation]. AB - We previously established a RET-transgenic mouse line (304/B6), in which skin melanosis, benign melanocytic tumors and malignant melanoma spontaneously develop. We found that the activities of RET tyrosine kinase, Erk and c-Jun are definitely upregulated in malignant melanoma in the RET-transgenic mice of line 304/B6. We also established another RET-transgenic mouse line (192), in which skin melanosis and benign melanocytic tumors, but not malignant melanoma, spontaneously develop. Ultraviolet irradiation induced malignant melanoma from benign tumors in the RET-transgenic mice of line 192, and promoted RET tyrosine kinase, Erk and c-Jun activities. These results suggest that the ultraviolet irradiation-mediated enhancement of RET and the activity of its downstream molecules play important roles in malignant melanoma development. PMID- 17334088 TI - [Management of occupational bladder cancer in Japan (Vol. 1)]. AB - By examining historical documents regarding occupational bladder cancer in Japan, we interpreted and followed the progress made in developing preventive measures against the outbreak of occupational bladder cancer in Japanese dye industries after World War II, and documented how these measures became well organized. During Dr. M. H. C. Williams's, who was an industrial physician for the British ICI Company, occasional visits to Japan, he encouraged the enforcement of such measures, considering them to be as important in occupational health in Japan as in Western countries. He received permission to implement these measures in Japanese dye companies. A urine cell diagnostic system was already being employed in Japanese industries as a method of diagnosing occupational bladder cancer, and its use was promoted by engineers, urologists, and pathologists even before the Industrial Safety and Health Law was enacted in 1972. It took about 10 years for these measures to become standardized industry-wide. The use of these measures has had a considerable effect on the early diagnosis of patients and extended patients' life spans. Eventually, the life spans of such patients became approximately the same as that of the average Japanese male. Some patients unfortunately died of occupational bladder cancer. Others were examined using these measures not only while employed but also after retirement. Therefore, some patients in whom occupational bladder cancer was detected are still alive at over eighty years of age. PMID- 17334089 TI - [Advances in "omics" technologies for toxicological research]. AB - Toxicology research can be applied to evaluate potential human health risks resulting from exposure to chemicals and other factors in the environment. The tremendous advances that have been made in high-throughput "omics" technologies (e.g., genomics, transcriptomics, proteomics and metabolomics) are providing good tools for toxicological research. Toxicogenomics is the study of changes in gene expression, protein and metabolite profiles, and combines the tools of traditional toxicology with those of genomics and bioinformatics. In particular, identification of changes in gene expression using DNA microarrays is an important method for understanding toxicological processes and obtaining an informative biomarker. Although these technologies have emerged as a powerful tool for clarifying hazard mechanisms, there are some concerns for the application of these technologies to toxicological research. This review summarizes the impact of "omics" technologies in toxicological study, followed by a brief discussion of future research. PMID- 17334090 TI - [Effects of kakisu (persimmon vinegar) on plasma antioxidant power and urinary 8 isoprostane level]. AB - OBJECTIVES: To clarify the antioxidative effects of kakisu (persimmon vinegar), plasma antioxidant power and urinary oxidative stress level in healthy subjects were measured using enzyme immunological assays. METHODS: Eighty-one subjects (age 30-69, 58.4 +/- 0.8) were randomly divided into two groups using a crossover design. Group A drank kakisu for 56 days starting in March, whereas group B drank kakisu for 54 days starting in June. Copper reducing equivalent level in plasma was measured as antioxidant power, and urinary 8-isoprostane (8-iso-prostaglandin F2alpha) level was measured as oxidative stress marker. RESULTS: Baseline plasma antioxidant power and urinary 8-isoprostane level showed no significant correlation among the subjects in this study. By drinking kakisu for 8 weeks, total antioxidant power significantly increased, and urinary 8-isoprostane level decreased. Total antioxidant power increased more markedly in group A than in group B. In contrast, urinary oxidative stress level decreased more markedly in group B than in group A. Smoking habits significantly correlated with urinary 8 isoprostane level. Males were more sensitive to the antioxidative effects of kakisu than females. CONCLUSIONS: Kakisu has antioxidative effects that increase plasma antioxidant power and reduce urinary 8-isoprostane level. Further study is needed to clarify the influence of season and gender on such antioxidative effects. PMID- 17334091 TI - [Estimation of effect of lipid lowering treatment on total mortality rate and its cost-effectiveness determined by intervention study of hypercholesterolemia]. AB - OBJECTIVES: Total cholesterol (TC) level reduction decreases coronary heart disease (CHD) risk, but it is also associated with an increase in non-CHD mortality rate. Our objectives are to estimate the effect of TC level reduction on total mortality and other mortalities in the Japanese population using published data and to analyze the cost-effectiveness of drug therapy. METHODS: We analyzed three data sets for the estimation. The first data set comprised Japanese mortality rates of cardiac diseases, cerebrovascular/other vascular diseases, malignancy, and all causes according to sex and age. The second data set comprised the distributions of serum TC levels in the Japanese population. The third data set comprised the relative risks of mortality rates for the above causes according to the TC level classified into discrete intervals of 20 mg/dl from an intervention study. We estimated the mortality rates of people aged 30 69, with each TC level classification group on the basis of each cause. On the assumption that TC level decreases from 240-259 mg/dl to 160-179 mg/dl or 180-199 mg/dl with drug therapy, we calculated the differences between the mortalities of the classification. When we found a positive effect of TC level reduction, we performed cost-effectiveness analyses of Number Needed to Treat (NNT). RESULTS: TC level reduction increased the mortality rates except for that of cardiac diseases, and the NNT for cardiac diseases was in the range of 4,202-17,533. The cost of simvastatin, for example, was 0.25-1.05 billion yen per year. CONCLUSIONS: TC level reduction from 240-259 mg/dl to 160-199 mg/dl leads to an increase in total mortality rate in the Japanese population. The treatment should be reevaluated from both viewpoints of risk benefit and cost-effectiveness. PMID- 17334092 TI - [Daily number of accidental injuries among elementary school children and school size factors in elementary schools]. AB - OBJECTIVES: The purpose of this study is to clarify the association between the daily number of accidental injuries and school size factors in elementary schools. METHODS: The accidental injuries that occurred during the school day among elementary school children were investigated in twenty-one schools for two month periods (from October to November) in 1999 and 2004. The relationship between the number of accidental injuries and school size factors (i.e. the numbers of school children and children per class) was analyzed by nonlinear regression analysis. The number of children injured and the frequency of accidental injuries were evaluated by school size. RESULTS: The ratio of the average number of injuries to all injuries was 1.79 per 100 children per day. The number of injuries in the small-sized schools was 2.36 per 100 children per day, and were respectively 1.29 and 1.57 in the middle- and large-sized schools. The number of injuries was small in middle-sized schools. As a result of the nonlinear regression analysis, a statistically significant quadratic equation was provided between the number of injuries per 100 children per day and the number of children per class. The number of injuries showed a minimum value for 26.7 children per class. The number of children injured during the investigation period was larger in the small-sized schools. In the small-sized schools, in comparison with the middle- and large-sized schools, the number of accidental injuries was smaller for boys. In the large-sized schools, there were more injuries inside the school building and during the lesson break times. CONCLUSION: large. In addition, it is suggested that the number of children injured was larger in small-sized schools. PMID- 17334093 TI - [Comparative study of five trialkyltin compounds: their metabolites in rat organs 24 hours after single oral treatment]. AB - OBJECTIVE: The objective of this study is to provide basic information on the metabolic fate of five trialkyltins, namely, trimethyltin, triethyltin, tripropyltin, tributyltin, and trioctyltin, in rats. METHODS: The levels of trialkyltin and its metabolites in the liver, kidneys, brain, and blood of rats and mice were determined 24h after single oral treatment with trimethyltin, triethyltin, tripropyltin, tributyltin, and trioctyltin by gas chromatography. The doses (as tin) of the trialkyltin compounds were 2.98 mg/kg for trimethyltin and triethyltin, 18.23 mg/kg for tripropyltin and tributyltin and 24.09 mg/kg for trioctyltin. RESULTS: For the trimethyltin and triethyltin treatments, no metabolites of either trialkyltin accumulated in the organs, except for the kidney in the triethyltin treatment. The levels of trimethyltin and triethyltin in the blood of the rats were markedly higher than those of the mice. For the tripropyltin and tributyltin treatments, the predominant metabolites in the liver and kidneys were found to be dialkyltins. Furthermore, despite the higher dose, the level of total tin in the organs 24 h after treatment with trioctyltin were markedly lower than those of the other trialkyltins tested. CONCLUSION: There are clear differences in the metabolic fates of the tin metabolites of the five trialkyItins studied. These results should be considered when carrying out toxicological research on trialkyltins. PMID- 17334094 TI - [Mutual relationship between prevalence statistics and mortality statistics in Parkinson's disease]. AB - OBJECTIVE: The purpose of this study is to determine whether the statistics from three published reports on Parkinson's disease (PD) are mutually interrelated and to clarify the relationship between the prevalence statistics and mortality statistics of PD. These statistics included data on "number of patients with PD (PD Patients)", "number of patients with PD receiving financial aid for treatment (PD Recipients)" as an indicator showing the prevalence of PD, and "number of deaths from PD (PD Deaths, i.e., mortality)". METHODS: The data on PD Patients, PD Recipients and PD Deaths were cited from "Patient Survey" by Ministry of Health, Labour and Welfare, a report by the Research Committee on Epidemiology of Intractable Diseases and "Vital Statistics of Japan" by Ministry of Health, Labour and Welfare, respectively. The expected PD Patients, PD Recipients and PD Deaths were calculated as products of their respective rates for the entire country and prefecture population, adjusting for a difference in population composition. Observed/expected number ratios (O/E ratio) of PD Patients, PD Recipients and PD Patients were calculated by prefecture. The correlation between the O/E ratios was examined. In addition, the relationships of the O/E ratios with the number of hospitals or physicians per person were examined. RESULTS: There were no significant correlations between the O/E ratios of PD Patients, PD Recipients or PD Deaths. The O/E ratio of PD Recipients significantly correlated with the numbers of hospitals and physicians per person. CONCLUSION: PD Patients and PD Recipients were included in number of people with PD and PD Deaths was derived from people with PD. However, these statistics do not necessarily reflect the prevalence of PD in each prefecture. When using these published statistics as an indicator of the prevalence of PD, it is necessary to clarify the purpose of their use and to comprehend their characteristics. PMID- 17334095 TI - [Pathological and biochemical studies of 30 Niigata autopsy cases related to Minamata disease]. AB - OBJECTIVES: To reevaluate pathologically and biochemically 30 autopsy cases related to Minamata disease (MD) in Niigata Prefecture (NP) and compare the findings with those of autopsy cases related to MD in Kumamoto Prefecture (KP). METHODS: Recently, a set of pathological materials of these 30 autopsy cases has been sent from the Brain Research Institute at the University of Niigata to the National Institute for Minamata Disease (NIMD). The materials from each autopsy case were reexamined at the NIMD. RESULTS: There were no postnatal and fetal cases of MD in the NP autopsy materials. The contents of total mercury (T-Hg), methylmercury (Me-Hg), inorganic mercury (I-Hg) and selenium were measured in the organs of cerebrum, cerebellum, liver and kidney. The contents of T-Hg, Me-Hg and I-Hg were much higher in two cases than in controls. The pathological findings leading to the diagnosis of MD in the NP cases were essentially the same as those in KP, including the peripheral nerve lesions. In the most severely affected case of MD in NP, formation of multiple vacuoles of various sizes was observed in the cerebellar cortex, which was never encountered in the KP cases. The KP lesions were similar to that observed in an acute case of Me-Hg-treated common marmoset studied in the NIMD. CONCLUSION: The pathological features were essentially the same between the adult cases of MD in NP and KP. PMID- 17334096 TI - Early pharmacy education at the University of Illinois. AB - "The study of chemistry is the most important as it is the most difficult of all the collateral branches of a pharmaceutist's education; the one that gives him the most power when applied in his professional pursuits, and the most reputation among the scientific. Chemistry is indeed the groundwork of every important process, and none can expect to excel who do not make it their study. The student of chemistry should, as early as practicable, get a mental outline grasp (if we may so speak) of the leading principles of the science". PMID- 17334097 TI - APhA Foundation history. PMID- 17334098 TI - [Comparison of the effects of two walk-through footbaths on the prevalence of digital dermatitis and interdigital dermatitis on a commercial dairy farm]. AB - This field trial was designed to evaluate the effect of treatment with copper chelate or formalin walk-through footbaths on the prevalence of digitalis dermatitis and interdigital dermatitis on a dairy farm. Although there was no difference in effect between the two types of footbath, the probability that interdigital dermatitis improved or remained stable was lower with the copper chelate footbath than with the formalin footbath. PMID- 17334099 TI - [Insulinoma and diabetes mellitus in a dog. Call to refer dogs with insulinoma for examination and surgery]. PMID- 17334100 TI - [Functional adaptation of cartilage in the horse from birth to fully grown is influenced by pressure: a biomechanical analysis]. PMID- 17334101 TI - [Limitations on accreditation]. PMID- 17334102 TI - [Zippered]. PMID- 17334103 TI - [Confidential reporting of prevention of farm animal cruelty. Slight rise in number of reports in 2006]. PMID- 17334104 TI - [October number Argos, bulletin of the Veterinary Historical Society]. PMID- 17334105 TI - ['Castration of a pregnant cat' asks for a collective point of view]. PMID- 17334106 TI - ['Castration of a pregnant cat' asks for a collective point of view]. PMID- 17334107 TI - [Management problems within veterinary clinics]. PMID- 17334108 TI - [European symposium about osteoarthritis in a dog]. PMID- 17334109 TI - [Report of the 2nd WVT-symposium]. PMID- 17334110 TI - Smoke-free nation. PMID- 17334111 TI - Preparing for an influenza pandemic. PMID- 17334112 TI - Chickenpox. PMID- 17334113 TI - Meet the Glugs. PMID- 17334114 TI - Health visitors' perceptions of their role in autism spectrum disorder. AB - This paper reports a study carried out in four primary care NHS trusts (PCTs) in the Midlands in order to inform inter-agency training and service planning around autism spectrum disorder (ASD). The aim of the study was to identify generic health visitors' perceptions of their role with families where children may have an ASD. The qualitative methodology is explained and key findings presented. Eleven health visitors participated as volunteers in one-to-one semi-structured interviews that were tape-recorded. Analysis of the data found some perceived tensions between health visitors' public health role and their work with individual families, especially when children had possible disabilities. Health visitors identified a role in the early identification of children developing atypically and in family support. Health visitors' perceptions are described and implications discussed. Recommendations are made regarding developmental assessment, training and service planning. PMID- 17334115 TI - Risk reduction and sudden infant death syndrome. AB - This article explores the concepts of 'risk' and 'risk reduction' in relation to sudden infant death syndrome (SIDS) and the implications for practice. Risk reduction is a term utilised in public health, which is usually linked to evidence-based outcomes. The Back to Sleep campaign is a high profile initiative which seeks to raise awareness of risk factors relating to SIDS and is largely credited with contributing to a significant reduction in the incidence of SIDS in the UK. Misunderstandings may occur between the terms 'risk reduction' and 'prevention' of health conditions and parents may feel that one equates to the other. There are also tensions which are inherent in defining risk in the context of SIDS. Certain measures may become 'shorthand' for a range of interventions and contributing factors. The practice of offering additional monitoring as support may reinforce a (mis)understanding about risk reduction and SIDS. There are implications for practice regarding how health professionals approach this issue, explain the guidelines and offer support.A clearer understanding of risk reduction would potentially enable bereaved parents to articulate their experiences without becoming too self critical in questioning their own consistent adherence to the accepted guidelines. PMID- 17334116 TI - Research training and leadership for midwives and health visitors. AB - We aimed to investigate the developing research capability in Midwifery and Health Visiting, as evidenced by doctoral degrees and post-doctoral careers. Our sources of information were: [1] an evaluation of research design in doctoral theses 1988-2002; [2] a search of the CINAHL, Medline, Allied and Complementary Medicine Database (AMED), British Nursing Index, and PsyclNFO databases for evidence of publication; and [3] an internet search for the eventual career trajectory of the postgraduates. To validate these data we looked retrospectively at a published survey of employment records of a sample of registered health visitors within academia. Doctoral designs had increasing diversity; though very few were clinically oriented. However, academic research leadership in the UK seems to be limited, especially in health visiting. Also, over a third of candidates graduated from 10 universities that do not have nursing or midwifery schools. We concluded that research capability is growing in midwifery and health visiting, but we could not identify a cohort sufficient to secure the development of evidence-based practice for the future of midwifery and health visiting. PMID- 17334117 TI - Vitamins, minerals and supplements: overview of vitamin C (5). PMID- 17334118 TI - Bereaved parents' campaign. PMID- 17334119 TI - Making the most of Agenda for Change (1). PMID- 17334120 TI - [The sunglasses left marks on the skin]. PMID- 17334121 TI - [Cholesterol embolism after left heart catheterization. Definitely not harmless!]. PMID- 17334122 TI - [Alcoholism in Germany. In alcohol consumption we are still at the top]. PMID- 17334123 TI - [Addiction leaves traces. Insight into the brain of alcoholics]. PMID- 17334124 TI - [Alcohol withdrawal therapy. For which patient ambulatory care only?]. PMID- 17334125 TI - [So patient education does not become a dispute. 5 legal traps one should know about]. PMID- 17334126 TI - [Erythema with pustules and no fever. What rages in this face?]. PMID- 17334127 TI - [Long-term treatment of obesity. How to increase your success rates]. PMID- 17334128 TI - [Successful treatment of obesity]. AB - Treating obesity can significantly reduce morbidity and mortality. Successful treatments comprise interdisciplinary long-term programs. The combined skills of physicians, psychologists, physiotherapists and dieticians are necessary to modify the patient's eating habits. With regard to dietetic measures, the combination of formula diets followed by reduction diets (CLD) has proved successful. Behavioral therapy in combination with professional physiotherapy can reduce the failure rate. In the event that dietetic measures fail, the medications sibutramine, orlistat and rimonabant are available. PMID- 17334129 TI - [Diagnosis and treatment of overweight in children and adolescents]. AB - With regard to obesity in children and adolescents in Germany, representative data are scarce, and there are no catamnestic data on the outcome of various therapeutic interventions. The study group "Obesity in Children and Adolescents" developed evidence-based guidelines for diagnosis, treatment and prevention, which are available for diagnostic and management strategies. The implementation of the standards for day-to-day care laid down there places the family doctor at the center of things, with the task of coordinating the diagnostic and therapeutic processes. The interdisciplinary specialized doctor's office could markedly improve the care afforded to obese children and adolescents, and their families, and serve as a contact point for regional preventive activities. PMID- 17334130 TI - [Surgical treatment of extreme obesity]. AB - Surgical treatment of extreme obesity can reliably achieve a significant weight loss. With interdisciplinary management, long-term therapeutic success is possible. Of particular importance, however, is the comprehensive education of the patient prior to surgery, and postoperative long-term care provided by the patient's own doctor. PMID- 17334131 TI - [Emergency check list: Asthma attack]. PMID- 17334132 TI - [Taping like in professional sports: targeted stabilization and early mobilization of the ankle]. AB - Taping is used in the prophylaxis, initial care, therapy and rehabilitation of injuries, such as for example, sprained ankles with damage to peroneal ligament, and for diseases and degenerative changes in the locomotor system. The tape stabilizes, activates and influences sensorimotoric perception (proprioception). PMID- 17334133 TI - [Perimenopausal symptoms]. PMID- 17334134 TI - [Reliable IGel for general practice. In this group pounds drop more easily]. PMID- 17334135 TI - Cultural competence can improve care, reduce risks. PMID- 17334136 TI - Rental PPO networks--be aware! A discount here may show up again and again. PMID- 17334137 TI - Hopes for SGR fix now rest with lame-duck session in November. PMID- 17334138 TI - Physician workforce predictions are a moving target. PMID- 17334139 TI - Economics of pressure-ulcer care: review of the literature on modern versus traditional dressings. AB - Published evidence suggests that some of the benefits of modern dressings--longer wear times and less frequent dressing changes--make them more cost-effective than traditional gauze dressings in pressure ulcer management. PMID- 17334140 TI - Dressing remedies: a concept for improving access to and use of dressings in nursing homes. AB - Delays in accessing dressings prescribed by general practitioners can result in the inappropriate use of dressings on more than one resident in nursing homes. The dressing remedies concept was developed to overcomes this problem. PMID- 17334141 TI - Bacterial resistance to silver in wound care and medical devices. AB - This review discusses the molecular and genetic evidence for silver resistance in bacteria isolated from skin wounds and medical devices with reference to a case study of resistant Enterobacter cloacae from the leg ulcers of an elderly woman. PMID- 17334142 TI - Venous leg ulcer treatment and practice--part 1: the causes and diagnosis of venous leg ulcers. AB - This article, the first of a series of four on venous leg ulceration, discusses theories relating to the pathophysiology underlying the condition, and the range of diagnostic procedures undertaken to establish that ulceration is of venous origin. PMID- 17334143 TI - An educational intervention for district nurses: use of electronic records in leg ulcer management. AB - OBJECTIVE: To evaluate district nurses' management of leg ulcer patients and the effects of an in-service education programme led by district nurses as local educators at primary health-care centres. METHOD: Data were collected from electronic patient records (EPRs), both before and after the educational intervention. Nineteen district nurses undertook a one-day course focusing on four themes: Doppler assessment and measurement of ankle brachial pressure index; compression treatment; patient education; nursing documentation. Fourteen acted as in-service educators; 12 educators completed the intervention. The EPRs were scrutinised with an audit tool. RESULTS: The documentation on the selected key areas for the management of patients with leg ulcers was generally sparse, although the educational intervention resulted in statistically significant effects on documentation in three areas. CONCLUSION: Further improvements in care are necessary, as are qualitative and quantitative studies to explore the large discrepancies between guidelines and everyday clinical practice in this field. PMID- 17334144 TI - Role of topical negative pressure in pressure ulcer management. AB - The literature suggests that topical negative pressure can be an effective treatment for severe pressure ulcers. However, research is needed on its effects on variables such as dressing change frequency, quality of life, pain relief and cost-effectiveness. PMID- 17334145 TI - Use of porcine dermal collagen graft and topical negative pressure on infected open abdominal wounds. AB - This article reports on two cases in which porcine dermal collagen grafts were used successfully alongside topical negative pressure therapy in order to close open abdominal wounds in which severe infection was present. PMID- 17334146 TI - Reducing noise and pain during TNP therapy for pilonidal disease. PMID- 17334147 TI - A review of the effect of tap water versus normal saline on infection rates in acute traumatic wounds. AB - This review seeks to determine whether using tap water rather than normal saline to irrigate acute traumatic wounds in the community has any effect on the rate of infection. The evidence suggests there is no such association. PMID- 17334148 TI - The successful management of a dehisced surgical wound with TNP following femoropopliteal bypass. AB - This case report discusses the use of topical negative pressure therapy on a suture line infected with methicillin-resistant Staphylococcus aureus in a patient with diabetes who had undergone a femoropopliteal bypass using an artificial graft. PMID- 17334149 TI - [Escherichia coli O157 in Dutch domesticated rabbits]. AB - Enterohaemorrhagic Escherichia coli (EHEC) has been detected in both wild and domesticated rabbits in other countries. The aim of this study was to determine whether the most pathogenic E. coli serotype, O157:H7, occurs in the Dutch domesticated rabbit population and thus could form a public health risk. To this end, faecal samples were collected from rabbits from two rabbit farms and 741 rabbits of different breeds and origin and analysed for E. coli O157:H7, using a combination of enrichment, immunomagnetic separation, selective culture, and PCR. E. coli O157:H7 was not detected in any of the samples. The results indicate that Dutch domesticated rabbits probably do not play a role in the infection of humans with E. coli O157:H7. PMID- 17334150 TI - [Health complaints and cognitive effects caused by exposure to MRI scanner magnetic fields]. PMID- 17334151 TI - [Buffy, the dog slayer]. PMID- 17334152 TI - ['The welfare of the swine farmer is first']. PMID- 17334153 TI - [40 years Voorjaarsdagen]. PMID- 17334154 TI - [Vaccination of more cats against feline herpesvirus 1]. PMID- 17334155 TI - [The CAO in veterinary clinics]. PMID- 17334156 TI - [Groep Groot Dagen 2006--Manage for a better practice!]. PMID- 17334157 TI - [The Horse Medicine Group runs in Hooge Mierde]. PMID- 17334158 TI - [New developments to improve patient compliance]. PMID- 17334159 TI - Health care authority rule short-sighted. PMID- 17334160 TI - West Virginia hospital preparedness: vision for the future. AB - The ability of hospitals to respond to individuals who have been chemically contaminated or victims of biologic warfare has been limited. This article reviews the current state of readiness of West Virginia hospitals and how new requirements have resulted in better preparedness for future events. Increased isolation capacity, hospital decontamination units and stockpiling of medications, forward deployment of chemical antidotes, electronic disease surveillance, and advanced credentialing of medical personnel are all key components in the overall plan for the state's preparedness. PMID- 17334161 TI - Gefitinib (IRESSA, ZD 1839) as a salvage treatment for patients with advanced non small cell lung cancer. AB - This study assessed the anti-tumor activity and tolerability of gefitinib (IRESSA, ZD 1839) in a series of patients with previously treated advanced non small cell lung cancer (NSCLC) seen at Charleston Area Medical Center in Charleston, W.Va. All patients were required to have proven advanced or metastatic NSCLC, along with meeting other study criteria. In 41 patients, the partial response rate was 7%, and 10% of patients achieved stable disease. Symptom improvement (dyspnea, anorexia) was reported in 44%. Mean survival for the entire group was 6.7 months (10.3 months for females, 3.7 months for males), with a 6-month survival rate of 33%. Adverse events were generally mild (grade I or II) and reversible and consisted mostly of diarrhea, rash, and anorexia. Although the major response rate was low, gefitinib (IRESSA, ZD 1839) demonstrated clinically meaningful anti-tumor activity with significant improvement in symptoms in this heavily pretreated group of patients with advanced NSCLC. PMID- 17334162 TI - Surgery for temporal lobe epilepsy. AB - Intractable epilepsy is a debilitating disease with significant associated morbidity and mortality. Uncontrolled epilepsy is socially disabling causing stigma, social exclusion, and often preventing employment. After an individual has tried and failed three or four of the standard anticonvulsants, it is very unlikely any further medications or combinations of medications will control the epilepsy. The major Neurology, Neurosurgery, and Epilepsy medical societies recommend all individuals with medically intractable epilepsy be evaluated in a comprehensive epilepsy program. In selected individuals, surgery for epilepsy has tremendous potential to cure or control intractable epilepsy. At West Virginia University Health Sciences Center, 48 individuals underwent surgery for intractable temporal lobe epilepsy over a 2.5 year period. Thirty-five (73%) of individuals were seizure free after surgery, and 96% were seizure free or significantly improved. Surgery for epilepsy has a high likelihood for success in medically intractable temporal lobe epilepsy, and is superior to medical treatment alone. PMID- 17334163 TI - A gender-based study of attitudes and practice characteristics of rural physicians in West Virginia. AB - Physician gender can affect the numbers of future rural health care providers since female physicians are less likely to enter rural practice, but the proportion of female U.S. medical students is increasing. This survey study of rural West Virginia physicians who were trained in the U.S. obtained information on demographics and prior practice intent, working time, practice characteristics, and satisfaction with practice and community for female vs. male physicians. Female physicians were more likely to report pre-existing intent to work in underserved areas and having higher proportions of Medicaid and uninsured patients, but fewer work hours and on-call services and less likelihood of providing hospital services. Initiatives to help address the shortage of rural providers could include residency program and community initiatives to address work flexibility and personal and spouse concerns for female physicians. PMID- 17334164 TI - Tension pneumoperitoneum resulting from endoscopic duodenal perforation: a case report. AB - Tension pneumoperitoneum is defined as an accumulation of free air within the peritoneal cavity sufficient to cause respiratory or hemodynamic compromise. We report a case of a 75-year-old woman who underwent upper endoscopy for evaluation of severe upper gastrointestinal hemorrhage. During the procedure, she developed massive abdominal distension, raising concern about possible perforation. Endoscopy was terminated and prompt surgical consultation obtained. This revealed massive abdominal distension, hypotension, and elevated airway pressures. Tension pneumoperitoneum was suspected. There was immediate decompression via a small umbilical incision, after which the patient's condition stabilized. A full exploration was then carried out, allowing definitive surgical treatment of both the source of bleeding and the perforation. We review the literature regarding this unusual event. PMID- 17334165 TI - Nursing Ethics conference on the globalisation of nursing: ethical, legal and political issues. PMID- 17334166 TI - Factors predicting nurses' consideration of leaving their job during the SARS outbreak. AB - Taiwan was affected by an outbreak of severe acute respiratory syndrome (SARS) in early 2003. A questionnaire survey was conducted to determine (1) the perceptions of risk of SARS infection in nurses; (2) the proportion of nurses considering leaving their job; and (3) work as well as non-work factors related to nurses' consideration of leaving their job because of the SARS outbreak. Nearly three quarters (71.9%) of the participants believed they were 'at great risk of exposure to SARS', 49.9% felt 'an increase in workload', and 32.4% thought that people avoided them because of their job; 7.6% of the nurses not only considered that they should not care for SARS patients but were looking for another job or considering resignation. The main predictors of nurses' consideration of leaving their job were shorter tenure, increased work stress, perceived risk of fatality from SARS, and affected social relationships. The findings are important in view of potential impending threats of pandemics such as avian influenza. PMID- 17334167 TI - Self-state of nurses in caring for SARS survivors. AB - The aim of this study was to analyze nurses' experiences of role strain when taking care of patients with severe acute respiratory syndrome (SARS). We adopted an interpretive/ constructivist paradigm. Twenty-one nurses who had taken care of SARS patients were interviewed in focus groups. The data were analyzed using thematic analysis. The self-state of nurses during the SARS outbreak evolved into that of professional self as: (1) self-preservation; (2) self-mirroring; and (3) self-transcendence. The relationship between self-state and reflective practice is discussed. PMID- 17334168 TI - Consent and assent to participate in research from people with dementia. AB - Conducting research with vulnerable populations involves careful attention to the interests of individuals. Although it is generally understood that informed consent is a necessary prerequisite to research participation, it is less clear how to proceed when potential research participants lack the capacity to provide this informed consent. The rationale for assessing the assent or dissent of vulnerable individuals and obtaining informed consent by authorized representatives is discussed. Practical guidelines for recruitment of and data collection from people in the middle or late stage of dementia are proposed. These guidelines were used by research assistants in a minimal risk study. PMID- 17334169 TI - Questionable requirement for consent in observational research in psychiatry. AB - Informed consent represents a cornerstone of the endeavours to make health care research ethically acceptable. Based on experience of qualitative research on power dynamics in nursing care in acute psychiatry, we show that the requirement for informed consent may be practised in formalistic ways that legitimize the researcher's activities without taking the patient's changing perception of the situation sufficiently into account. The presentation of three patient case studies illustrates a diversity of issues that the researcher must consider in each situation. We argue for the necessity of researchers to base their judgement on a complex set of competencies. Consciousness of research ethics must be combined with knowledge of the challenges involved in research methodology in qualitative research and familiarity with the therapeutic arena in which the research is being conducted. The article shows that the alternative solution is not simple but must emphasize the researcher's ability to doubt and be based on an awareness of the researcher's fallibility. PMID- 17334170 TI - The Terminal: a tale of virtue. AB - The movie, The terminal, is used to illustrate MacIntyre's description of virtue ethics. The terminal is a mythical tale about a traveler, Viktor Navorski, who is stranded by circumstances in a New York airport. Viktor is a person who, without a strict reliance on duty or rules, has developed the disposition to act well despite variation in his circumstances. His character is revealed in contrast to that of three other characters: a cleaner, a flight attendant and the airport manager. Stories like this one may be a good way to open dialogue among clinicians about being virtuous as a practitioner. Such dialogue may make striving to be virtuous an acceptable goal for practitioners and less like an idealistic, pseudo-goal for those aiming for sainthood. PMID- 17334171 TI - Why hospice nurses need high self-esteem. AB - This article discusses the relationship between personal and professional qualities in hospice nurses. We examine the notion of self-esteem in personal and professional identity. The focus is on two questions: (1) what is self-esteem, and how is it related to personal identity and its moral dimension? and (2) how do self-esteem and personal identity relate to the professional identity of nurses? We demonstrate it is important that the moral and personal goals in nurses' life coincide. If nurses' personal view of the good life is compatible with their experiences and feelings as professionals, this improves their performance as nurses. We also discuss how good nursing depends on the responses that nurses receive from patients, colleagues and family; they make nurses feel valued as persons and enable them to see the value of the work they do. PMID- 17334172 TI - QALY: an ethical issue that dare not speak its name. AB - The current British Government's policy towards resource allocation for health care has been informed by the commissioned Wanless Report. This makes a case for the use of quality adjusted life years (QALYs) to form a rationale for resourcing health care and has implications for the staff and patients who work in and use the health service. This article offers a definition of the term 'QALY' and considers some of the strengths and weaknesses of this approach to resource distribution. An account is also given of an alternative formula, the DALY (disability adjusted life years), which can address some of the problems that are associated with QALYs. The values of the public, patients and nurses are identified and linked to the potential effect of a QALY formula. The implications of QALY use are applied to the health care of patients and a discussion is offered with regard to whether this method of resource allocation can be considered as just. PMID- 17334173 TI - Autonomy, responsibility and the Italian Code of Deontology for Nurses. AB - This article is a first assessment of the Italian Code of deontology for nurses (revised in 1999) on the basis of data collected from focus groups with nurses taking part in the Ethical Codes in Nursing (ECN) project. We illustrate the professional context in which the Code was introduced and explain why the 1999 revision was necessary in the light of changes affecting the Italian nursing profession. The most remarkable findings concern professional autonomy and responsibility, and how the Code is thought of as a set of guidelines for nursing practice. We discuss these issues, underlining that the 1999 Code represents a valuable instrument for ethical reflection and examination, a stimulus for putting the moral sense of the nursing profession into action, and that it represents a new era for professional nursing practice in Italy. The results of the analysis also deserve further qualitative study and future consideration. PMID- 17334174 TI - A novel framework for reflecting on the functioning of research ethics review panels. AB - In the past decade structures and processes for the ethical review of UK health care research have undergone rapid change. Although this has focused users' attention on the functioning of review committees, it remains rare to read a substantive view from the inside. This article presents details of processes and findings resulting from a novel structured reflective exercise undertaken by a newly formed research ethics review panel in a university school of nursing and midwifery. By adopting and adapting some of the knowledge to be found in the art and science of malt whisky tasting, a framework for critical reflection is presented and applied. This enables analysis of the main contemporary issues for a review panel that is primarily concerned with research into nursing education and practice. In addition to structuring the panel's own literary narrative, the framework also generates useful visual representation for further reflection. Both the analysis of issues and the framework itself are presented as of potential value to all nurses, health care professionals and educationalists with an interest in ethical review. PMID- 17334176 TI - Is there a role for PCR-SSCP among the methods for missense mutation detection of TP53 gene? AB - Mutation analysis methods have increased in variety during the past years. High throughput microarray methods have especially increased in popularity. However, new methods require reference points, and not all of the methods are equal in sensitivity and specificity. Furthermore, the detection of unknown missense mutations, such as unknown TP53 mutations in human tumors, for clinical purposes requires great accuracy, which may be difficult to acquire with the current high throughput methods. For these reasons, the classical methods, such as PCR-manual sequencing and PCR-SSCP, are still valuable and necessary. PMID- 17334177 TI - Acute and repeat-dose toxicity studies of the (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH), an albumin-binding prodrug of the anticancer agent doxorubicin. AB - The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that demonstrates superior antitumor efficacy in murine tumor models, and has been evaluated in a phase I study. In order to establish the toxicity profile of this prodrug, acute and repeat-dose toxicity studies were performed with DOXO-EMCH in CD1-mice, Sprague-Dawley rats and Beagle dogs. Although the objective of the acute toxicity studies was not the determination of LD50 values, the LD50 of DOXO EMCH was >60 mg/kg doxorubicin equivalents in both male and female mice (the LD50 of doxorubicin in CD-1 mice is -12 mg/kg). In Sprague-Dawley rats, the LD50 was 23.4 and 45.9 mg/kg doxorubicin equivalents for males and females, respectively. For comparison, the LD50 of doxorubicin in Sprague-Dawley rats is -10.5 mg/kg. The major clinical sign noted following intravenous administration of DOXO-EMCH in mice and rats was a dose-dependent peripheral neuropathy which, in general, developed as a delayed toxicity 1-3 weeks after application. The observed neurotoxicity has been well documented for Sprague-Dawley rats treated with doxorubicin at a dose of 5 and 10 mg/kg. In Beagle dogs, LD10 was not reached for DOXO-EMCH at 4.5 mg/kg doxorubicin equivalents. A four-cycle intravenous study with DOXO-EMCH at dose levels of 4 x 2.5, 5.0 or 7.5 mg/kg doxorubicin equivalents in rats revealed approximately three-fold less side effects on the hemolymphoreticular system when compared to 4 x 2.5 mg/kg doxorubicin dose, whereas effects on the testes/oligospermia seem to be comparable between both drugs at equitoxic dose. A No Observable Adverse Effect Level (NOAEL) for DOXO EMCH of 4 x 2.5 mg/kg doxorubicin equivalents was established in this study. This dose is equivalent to the maximum tolerated dose (MTD) of doxorubicin in rats. In a two-cycle study over a period of 6 weeks in Beagle dogs (intravenous administration of DOXO-EMCH at dose levels of 1.5, 3.0 or 4.5 mg/kg doxorubicin equivalents), dose-related systemic histamine-like reactions within the first 3 hours after injection were noted in all treated groups. Only transient and temporary effects on hematology, urinary function, as well as on histopathology in mid- and/or high-dose animals, were observed. The low dose of 2 x 1.5 mg/kg was considered to be the NOAEL in this study, which is equivalent to twice the MTD o f doxorubicin i nBeagle dogs. In summary, the toxicity studies with DOXO EMCH in mice, rats or dogs have not identified any other special toxicity when compared to the toxicity data for doxorubicin. Preclinical tolerance of DOXO-EMCH was higher in mice, rats and dogs compared to doxorubicin. A dose of 20 mg/m2 doxorubicin equivalents was recommended as the starting dose for a phase I study with DOXO-EMCH. PMID- 17334178 TI - Determination of two mercapturic acids related to crotonaldehyde in human urine: influence of smoking. AB - Crotonaldehyde, an alpha,beta-unsaturated aldehyde, and a potent alkylating agent, is present in many foods and beverages, ambient air and tobacco smoke. A previous study indicated that two metabolites, 3-hydroxy-1 methylpropylmercapturic acid (HMPMA) and 2-carboxyl-l-methylethylmercapturic acid (CMEMA), were excreted in rat urine after subcutaneous injection of crotonaldehyde. Herein, we report the development of a method based on liquid chromatography with tandem mass spectrometry (LC-MS/MS) and deuterated analytes as internal standards, for the determination of HMPMA and CMEMA in human urine. The limits of quantification of the method were 92 and 104 ng/mL for HMPMA and CMEMA, respectively. The calibration curves for both compounds were linear up to 7500 ng/mL with R2 >0.99. It was found that cigarette smokers excreted about three to five-fold more HMPMA, and only slightly elevated amounts of CMEMA, in their urine compared to nonsmokers. In smokers, we also found significant correlations between the urinary excretion levels of HMPMA (but not CMEMA) and several markers of exposure for smoking, including the daily cigarette consumption, carbon monoxide in exhaled breath, salivary cotinine, and nicotine plus five of its major metabolites in urine. Smoking cessation or switching from smoking conventional cigarettes to experimental cigarettes with lower crotonaldehyde delivery led to significant reductions of urinary HMPMA excretion, but not CMEMA excretion. Alcohol consumption did not influence either urinary HMPMA or CMEMA excretion. We conclude that HMPMA is a potentially useful biomarker for smoking-related exposure to crotonaldehyde. PMID- 17334179 TI - Poisons admissions in Edinburgh 1981-2001: agent trends and predictors of hospital readmissions. AB - Self-poisoning is a major public health problem. This study describes patterns of admissions and readmissions from self-poisoning to the Royal Infirmary of Edinburgh from 1981 to 2001. A database on hospital discharges with a diagnosis (ICD-9/10) of poisoning between 1981 and 2001 was used. Annual admissions were described for seven main drug categories, and proportions of patients readmitted within 1-5 years from first admission, were computed for each category. Cox proportional hazards regression was used to evaluate prognostic factors for readmission risk over 1981-2001. For both sexes, admissions increased from the early to mid 1990s, and declined thereafter. The proportion readmitted varied with the drug taken at first admission, from 11.9% (95% CI: 10.8-13%) for non opiate analgesics, to 17.6% (16.5-18.7%) for benzodiazepines. Deprivation was positively related to readmission risk after first admissions with paracetamol (P < 0.001) and benzodiazepines (P < 0.001). Timing of first admissions involving paracetamol (P < 0.01), benzodiazepines (P < 0.001), antidepressants (P < 0.001), non-opiate analgesics (P < 0.001), and opiates (P < 0.05), was inversely associated with readmission risk. In patients admitted for drug overdose, readmission risk is influenced by type of drug taken at first admission. Information on drug type used in self-poisoning may assist in identifying patients at risk for future events, and in reducing hospital readmissions. PMID- 17334180 TI - Does unintentional ingestion of ethylene glycol represent a serious risk? AB - The objective of this study was to evaluate data retrospectively on accidental ingestion of ethylene glycol (EG), based on calls to the Czech Toxicological Information Centre and from toxicological laboratories, in the years 2000-2004. All patients who ingested a known amount of EG and/or subjects with measured serum EG levels were included. A variety of clinical and laboratory parameters was collected. The medical records of 86 subjects, who had ingested from one to three swallows of EG, were analysed. The following findings emerged-metabolic acidosis (41%), vomiting (36%), nephrotoxicity (10%), and CNS depression (9%). In 15 children, the time interval between ingestion and hospitalisation was 1 hour or less. Ethanol was given to 12 children (four as first aid), and none developed hypoglycaemia. Of the 71 adults, 93% were treated with ethanol (19 as first aid). No side effects were documented. Seventeen patients received haemodialysis (HD). Two patients recovered without HD; their EG levels were higher than in the HD treated patients. Unintentional EG ingestion usually involves ingestion of a small amount of EG, and was connected with mild signs of intoxication. Early therapy with ethanol alone appears sufficient in such cases, and represents no risk of adverse effects. PMID- 17334181 TI - Structure and science. PMID- 17334182 TI - Impact of a citywide blackout on an urban emergency medical services system. AB - INTRODUCTION: On 14 August 2003, New York City and a large portion of the northeastern United States experienced the largest blackout in the history of the country. An analysis of such a widespread disaster on emergency medical service (EMS) operations may assist in planning for and managing such disasters in the future. METHODS: A retrospective review of all EMS activity within New York City's 9-1-1 emergency telephone system during the 29 hours during which all or parts of the city were without power (16:11 hours (h) on 14 August 2003 until 21:03 h on 15 August 2003) was performed. Control periods were established utilizing identical time periods during the five weeks preceding the blackout. RESULTS: Significant increases were identified in the overall EMS demand (7,844 incidents vs. 3,860 incidents; p < 0.001) as well as in 20 of the 62 call-types of the system, including cardiac arrests (119 vs. 76, p = 0.043). Significant decreases were found only among calls related to psychological emergencies (114 vs. 221; p = 0.006) and drug- or alcohol-related emergencies (78 vs. 146; p = 0.009). Though median response times increased by only 60 seconds, median call processing times within the 9-1-1 emergency telephone system EMS dispatch center of the city increased from 1.1 to 5.5 minutes. CONCLUSIONS: The citywide blackout resulted in dramatic changes in the demands upon the EMS system of New York City, the types of patients for whom EMS providers were assigned to provide care, and the dispositions for those assignments. During this time of increased, system wide demand, the use of cross-trained firefighter and first-responder engine companies resulted in improved response times to cardiac arrest patients. Finally, the ability of the EMS dispatch center to process the increased requests for EMS assistance proved to be the rate-limiting step in responding to these emergencies. These findings will prove useful in planning for future blackouts or any disaster that may broadly impact the infrastructure of a city. PMID- 17334183 TI - Control of hemorrhage in critical femoral or inguinal penetrating wounds--an ultrasound evaluation. AB - INTRODUCTION: Exsanguination from a femoral artery wound can occur in seconds and may be encountered more often due to increased use of body armor. Some military physicians teach compression of the distal abdominal aorta (AA) with a knee or a fist as a temporizing measure. OBJECTIVE: The objective of this study was to evaluate if complete collapse of the AA was feasible and with what weight it occurs. METHODS: This was a prospective, interventional study at a Level-I, academic, urban, emergency department with an annual census of 80,000 patients. Written, informed consent was obtained from nine male volunteers after Institutional Research Board approval. Any patient who presented with abdominal pain or had undergone previous abdominal surgery was excluded from the study. Subjects were placed supine on the floor to simulate an injured soldier. Various dumbbells of increasing weight were placed over the distal AA, and pulsed-wave Doppler measurements were taken at the right common femoral artery (CFA). Dumbbells were placed on top of a tightly bundled towel roughly the surface area of an adult knee. Flow measurements at the CFA were taken at increments of 20 pounds. This was repeated with weight over the proximal right artery iliac and distal right iliac artery to evaluate alternate sites. Descriptive statistics were utilized to evaluate the data. RESULTS: The mean velocity through the CFA was 75.8 cm/sec at 0 pounds. Compression of the AA ranging 80 to 140 pounds resulted in no flow in the CFA. A steady decrease in mean flow velocity was seen starting with 20 pounds. Flow velocity decreased more rapidly with compression of the proximal right iliac artery, and stopped in all nine volunteers by 120 pounds of pressure. For all nine volunteers, up to 80 pounds of pressure over the distal iliac artery failed to decrease CFA flow velocity, and no subject was able to tolerate more weight at that location. CONCLUSION: Flow to the CFA can be stopped completely with pressure over the distal AA or proximal iliac artery in catastrophic wounds. Compression over the proximal iliac artery worked best, but a first responder still may need to apply upward of 120 pounds of pressure to stop exsanguination. PMID- 17334184 TI - Terrorism and mental health in the rural Midwest. AB - INTRODUCTION: Since the terrorist attacks of 11 September 2001, the amount of terrorism preparedness training has increased substantially. However, gaps continue to exist in training for the mental health casualties that result from such events. Responders must be aware of the mental health effects of terrorism and how to prepare for and buffer these effects. However, the degree to which responders possess or value this knowledge has not been studied. METHODS: Multi disciplinary terrorism preparedness training for healthcare professionals was conducted in Kansas in 2003. In order to assess knowledge and attitudes related to mental health preparedness training, post-test surveys were provided to 314 respondents 10 months after completion of the training. Respondents returned 197 completed surveys for an analysis response rate of 63%. RESULTS: In general, the results indicated that respondents have knowledge of and value the importance of mental health preparedness issues. The respondents who reported greater knowledge or value of mental health preparedness also indicated significantly higher ability levels in nationally recognized bioterrorism competencies (p < 0.001). CONCLUSIONS: These results support the need for mental health components to be incorporated into terrorism preparedness training. Further studies to determine the most effective mental health preparedness training content and instruction modalities are needed. PMID- 17334185 TI - Rapid needs assessment of Hurricane Katrina evacuees-Oklahoma, September 2005. AB - INTRODUCTION: On 04 September 2005, 1,589 Hurricane Katrina evacuees from the New Orleans area arrived in Oklahoma. The Oklahoma State Department of Health conducted a rapid needs assessment of the evacuees housed at a National Guard training facility to determine the medical and social needs of the population in order to allocate resources appropriately. METHODS: A standardized questionnaire that focused on individual and household evacuee characteristics was developed. Households from each shelter building were targeted for surveying, and a convenience sample was used. RESULTS: Data were collected on 197 households and 373 persons. When compared with the population of Orleans Parish, Louisiana, the evacuees sampled were more likely to be male, black, and 45-64 years of age. They also were less likely to report receiving a high school education and being employed pre-hurricane. Of those households of > 1 persons, 63% had at least one missing household member. Fifty-six percent of adults and 21% of children reported having at least one chronic disease. Adult women and non-black persons were more likely to report a pre-existing mental health condition. Fourteen percent of adult evacuees reported a mental illness that required medication pre hurricane, and eight adults indicated that they either had been physically or sexually assaulted after the hurricane. Approximately half of adults reported that they had witnessed someone being severely injured or dead, and 10% of persons reported that someone close to them (family or friend) had died since the hurricane. Of the adults answering questions related to acute stress disorder, 50% indicated that they suffered at least one symptom of the disorder. CONCLUSIONS: The results from this needs assessment highlight that the evacuees surveyed predominantly were black, of lower socio-economic status, and had substantial, pre-existing medical and mental health concerns. The evacuees experienced multiple emotional traumas, including witnessing grotesque scenes and the disruption of social systems, and had pre-existing psychopathologies that predisposed this population to post-traumatic stress disorder (PTSD). When disaster populations are displaced, mental health and social service providers should be available immediately upon the arrival of the evacuees, and should be integrally coordinated with the relief response. Because the displaced population is at high risk for disaster-related mental health problems, it should be monitored closely for persons with PTSD. This displaced population will likely require a substantial re-establishment of financial, medical, and educational resources in new communities or upon their return to Louisiana. PMID- 17334186 TI - Pattern of drug prescription and utilization among Bam residents during the first six months after the 2003 Bam earthquake. AB - INTRODUCTION: It is important to identify what kinds of drugs are required by disaster-affected populations so that appropriate donations are allocated. On 26 December 2003, an earthquake with an amplitude of 6.3 on the Richter scale struck southeastern Iran, decimating the city of Bam. In this study, the most frequently utilized and prescribed drugs for Bam outpatients during the first six months after the Bam Earthquake were investigated. METHODS: In this descriptive, cross sectional study, the data were collected randomly from 3,000 prescriptions of Bam outpatients who were examined by general practitioners from Emergency Medical Assistance Teams in 12 healthcare centers during the first six months after the Bam Earthquake. The data were analyzed for: (1) patient sex; (2) number of drugs/prescriptions; (3) drug category; (4) drug name (generic or brand); (5) route of administration; (6) percent of visits where the most frequent drug categories were prescribed; and (7) the 25 most frequently prescribed drugs, using World Health Organization (WHO) indicators of drug use in health facilities. RESULTS: Male patients represented 47.4% and females 52.6% of the total number of outpatients. The mean number of drugs/prescriptions was 3.5 per outpatient. Oral administration was the most frequent method of administration (81.7%), followed by injections (10.9%). Respiratory drugs were the most frequently used drugs (14.2%), followed by analgesics/non-steroidal anti inflammatory drugs (NSAIDs) (11.3%), antibacterials (11.2%), gastrointestinal (GI) drugs (9.6%), and central nervous system drugs (7%). Penicillins (6.8%), cold preparations (8%), and systemic anti-acids (ranitidine and omeprazole) were among the 25 most frequently used drugs by outpatients and inhabitants of Bam during the first six months after the Bam Earthquake. CONCLUSION: Respiratory, analgesic, antibacterial, GI, and psychiatric medications were among the most commonly prescribed pharmaceuticals after the catastrophic Bam Earthquake. The results of this study may help to predict the needs of patients during future disasters and prevent unnecessary donations of medicine. PMID- 17334187 TI - Hawaii physician and nurse bioterrorism preparedness survey. AB - INTRODUCTION: Physicians and nurses are integral components of the public health bioterrorism surveillance system. However, most published bioterrorism preparedness surveys focus on gathering information related to self-assessed knowledge or perceived needs and abilities. OBJECTIVE: A survey of physicians and nurses in Hawaii was conducted to assess objective knowledge regarding bioterrorism agents and diseases and perceived response readiness for a bioterrorism event. METHODS: During June and July 2004, an anonymous survey was mailed up to three times to a random sample of all licensed physicians and nurses residing in Hawaii. RESULTS: The response rate was 45% (115 of 255) for physicians and 53% (146 of 278) for nurses. Previous bioterrorism preparedness training associated significantly with knowledge-based test performance in both groups. Only 20% of physicians or nurses had had previous training in bioterrorism preparedness, and < 15% felt able to respond effectively to a bioterrorism event. But, > 70% expressed willingness to assist the state in the event of a bioterrorist attack. CONCLUSIONS: Additional bioterrorism preparedness training should be made available through continuing education and also should become a component of both medical and nursing school curricula. It is important to provide the knowledge necessary for physicians and nurses to improve their ability to perform in the event of a bioterrorist attack. PMID- 17334188 TI - A pilot assessment of hospital preparedness for bioterrorism events. AB - OBJECTIVE: Lessons on question content and refinement of a 2003 Agency for Healthcare Research and Quality-Health Resources Services Administration (AHRQ HRSA) pilot hospital preparedness assessment tool designed to capture activities in more detail than previous studies are reported in this study. METHODS: Responses from fixed-choice questions, including organizational and geographical differences, were analyzed using the chi-square test. Open-ended questions were evaluated qualitatively. RESULTS: Of the respondents, 91% had developed plans and 97% designated a bio-event coordinator, but only 47% had allocated funds. Urban hospitals were more likely to participate in regional infectious disease monitoring. Hospitals that participated in a network were more likely to fund preparedness, share bio-event coordinators and medical directors, and provide advanced training. CONCLUSIONS: Several issues deserve further study: (1) hospital networks may provide the structure to promote preparedness; (2) specific procedures (e.g., expanding outpatient treatment capacity) have not been tested; and (3) special attention should be directed towards integrating non-urban hospitals into regional surveillance systems to ensure early identification of infectious disease outbreaks. PMID- 17334189 TI - Performance indicators as quality control for testing and evaluating hospital management groups: a pilot study. AB - INTRODUCTION: An important issue in disaster medicine is the establishment of standards that can be used as a template for evaluation. With the establishment of standards, the ability to compare results will improve, both within and between different organizations involved in disaster management. OBJECTIVE: Performance indicators were developed for testing in simulations exercises with the purpose of evaluating the skills of hospital management groups. The objective of this study is to demonstrate how these indicators can be used to create numerically expressed results that can be compared. METHODS: Three different management groups were tested in standardized simulation exercises. The testing took place according to the organization's own disaster plan and within their own facilities. Trained observers used a pre-designed protocol of performance indicators as a template for the evaluation. RESULTS: The management group that scored lowest in management skills also scored lowest in staff skills. CONCLUSION: The use of performance indicators for evaluating the management skills of hospital groups can provide comparable results in testing situations and could provide a new tool for quality improvement of evaluations of real incidents and disasters. PMID- 17334190 TI - Predictive effect of out-of-hospital time in outcomes of severely injured young adult and elderly patients. AB - INTRODUCTION: The importance of accessing care within the first hour after injury has been a fundamental tenet of trauma system planning for 30 years. However, the scientific basis for this belief either has been missing or largely derived from case series from trauma centers. This study sought to determine the correlation between prehospital times and outcomes among severely injured elderly patients. METHODS: This is a cross-sectional, observational study. All adults (> or = 18 years of age) with acute trauma as defined by The International Classification of Diseases Ninth Edition, Clinical Modification diagnostic codes and E-codes were included. Poisonings, single system burns, and late effects of injury were excluded. Chi-square and Student's t-test were used for significance testing. To assess the predictive effects of prehospital time and outcomes, three independent logistic regression models were constructed for both young and elderly groups, with hospital length of stay, mortality, and complications as individual dependent variables. Statistical significance was set at the 0.05 level. RESULTS: Of 41,041 cases, 37,276 were > or = 18 years of age. Of the 1,866 with an Injury Severity Score (ISS) > 15, 1,205 were young and 661 elderly. Logistic regression results showed that prehospital time correlated significantly with hospital length of stay (p = 0.001) and complications (p = 0.016), but not with mortality (p = 0.264) among young patients, whereas in the elderly group pre-hospital time had no significant predictive effect for length of stay, complications, or mortality (p = 0.512, p = 0.512, and p = 0.954 respectively). CONCLUSION: This population-based study has demonstrated that prehospital time correlates with length of stay and complications in young patients. In elderly patients, prehospital time failed to show correlation with any outcomes measured. PMID- 17334191 TI - Percutaneous transtracheal ventilation: resuscitation bags do not provide adequate ventilation. AB - INTRODUCTION: Percutaneous, transtracheal jet ventilation (PTJV) is an effective way to ventilate both adults and children. However, some authors suggest that a resuscitation bag can be utilized to ventilate through a cannula placed into the trachea. HYPOTHESIS: Percutaneous transtracheal ventilation (PTV) through a 14 gauge catheter is ineffective when attempted using a resuscitation bag. METHODS: Eight insufflation methods were studied. A 14-gauge intravenous catheter was attached to an adult resuscitation bag, a pediatric resuscitation bag, wall source (wall) oxygen, portable-tank oxygen with a regulator, and a jet ventilator (JV) at two flow rates. The resuscitation bags were connected to the 14-gauge catheter using a 7 mm adult endotracheal tube adaptor connected to a 3 cc syringe barrel. The wall and tank oxygen were connected to the 14-gauge catheter using a three-way stopcock. The wall oxygen was tested with the regulator set at 15 liters per minute (LPM) and with the regulator wide open. The tank was tested with the regulator set at 15 and 25 LPM. The JV was connected directly to the 14 gauge catheter using JV tubing supplied by the manufacturer. Flow was measured using an Ohmeda 5420 Volume Monitor. A total of 30 measurements were taken, each during four seconds of insufflation, and the results averaged (milliliters (ml) per second (sec)) for each device. RESULTS: Flow rates obtained using both resuscitation bags, tank oxygen, and regulated wall oxygen were extremely low (adult 215 +/- 20 ml/sec; pediatric 195 +/- 19 ml/sec; tank 358 +/- 13 ml/sec; wall at 15 l/min 346 +/- 20 ml/sec). Flow rates of 1,394 +/- 13 ml were obtained using wall oxygen with the regulator wide open. Using the JV with the regulator set at 50 pounds per square inch (psi), a flow rate of 1,759 +/- 40 was obtained. These were the only two methods that produced flow rates high enough to provide an adequate tidal volume to an adult. CONCLUSIONS: Resuscitation bags should not be used to ventilate adult patients through a 14-gauge, transtracheal catheter. Jet ventilation is needed when percutaneous transtracheal ventilation is attempted. If jet ventilation is attempted using oxygen supply tubing, it must be connected to an unregulated oxygen source of at least 50 psi. PMID- 17334192 TI - A four-step approach for establishment of a national medical response to mega terrorism. AB - A simplified, four-step approach was used to establish a medical management and response plan to mega-terrorism in Israel. The basic steps of this approach are: (1) analysis of a scenario based on past incidents; (2) description of relevant capabilities of the medical system; (3) analysis of gaps between the scenario and the expected response; and (4) development of an operational framework. Analyses of both the scenario and medical abilities led to the recommendation of an evidence-based contingency plan for mega-terrorism. An important lesson learned from the analyses is that a shortage in medical first responders would require the administration of advanced life support (ALS) by paramedics at the scene, along with simultaneous, rapid evacuation of urgent casualties to nearby hospitals by medics practicing basic life support (BLS). Ambulances and helicopters should triage casualties from inner to outer circle hospitals secondarily, preferentially Level-1 trauma centers. In conclusion, this four-step approach based on scenario analysis, mapping of medical capabilities, detection of bottlenecks, and establishment of a unique operational framework, can help other medical systems develop a response plan to mega-terrorist attacks. PMID- 17334193 TI - Who should worry for the "worried well"? Analysis of mild casualties center drills in non-conventional scenarios. AB - INTRODUCTION: A mass toxicological event (MTE) caused by an act of terrorism or an industrial incident can create large numbers of ambulatory casualties suffering from mild intoxication, acute stress reaction (ASR), and exacerbation of chronic diseases or iatrogenic insult (such as atropine overdose). The logistical and medical management of this population may present a challenge in such a scenario. The aim of this article is to describe the concept of the Israeli Home Front Command (HFC) of a "Mild Casualties Center" (MCC) for a chemical scenario, and to analyze the results of two large-scale drills that have been used to evaluate this concept. METHODS: Two large-scale drills were conducted. One MCC drill was located in a school building and the second MCC drill was located in a basketball stadium. These medical centers were staffed by physicians, nurses, and medics, both military (reservists) and civilian (community, non-hospital teams). Two hundred simulated patients entered the MCC during each of the drills, and drill observers assessed how these patients were managed for two hours. RESULTS: Of the casualties, 28 were treated in the "medical treatment site", 10 of which were relocated to a nearby hospital. Only four casualties were treated in the large "mental care site", planned for a much higher burden of "worried well" patients. Documentation of patient data and medical care was sub-optimal. CONCLUSION: A MCC is a logistically suitable solution for the challenge of managing thousands of ambulatory casualties. The knowledge of the medical team must be bolstered, as most are unfamiliar with both nerve gas poisoning and with ASR. Mild casualties centers should not be located within hospitals and must be staffed by non-hospital, medical personnel to achieve the main task of allowing hospital teams to focus on providing medical care to the moderate and severe nerve gas casualties, without the extra burden of caring for thousands of mild casualties. PMID- 17334194 TI - Out-of-hospital resuscitation: have we gone too far? AB - Americans are living longer and are more likely to be chronically or terminally ill at the time of death. Although surveys indicate that most people prefer to die at home, the majority of people in the United States die in acute care hospitals. Each year, approximately 400,000 persons suffer sudden cardiac arrest in the US, the majority occurring in the out-of-hospital setting. Mortality rates are high and reach almost 100% when prehospital care has failed to restore spontaneous circulation. Nonetheless, patients who receive little benefit or may wish to forgo life-sustaining treatment often are resuscitated. Risk versus harm of resuscitation efforts can be differentiated by various factors, including cardiac rhythm. Emergency medical services policy regarding resuscitation should consider its utility in various clinical scenarios. Patients, family members, emergency medical providers, and physicians all are important stakeholders to consider in decisions about out-of-hospital cardiac arrest. Ideally, future policy will place greater emphasis on patient preferences and quality of life by including all of these viewpoints. PMID- 17334195 TI - Assessing levels of hospital emergency preparedness. AB - INTRODUCTION: Emergency preparedness can be defined by the preparedness pyramid, which identifies planning, infrastructure, knowledge and capabilities, and training as the major components of maintaining a high level of preparedness. The aim of this article is to review the characteristics of contingency plans for mass-casualty incidents (MCIs) and models for assessing the emergency preparedness of hospitals. CHARACTERISTICS OF CONTINGENCY PLANS: Emergency preparedness should focus on community preparedness, a personnel augmentation plan, and communications and public policies for funding the emergency preparedness. The capability to cope with a MCI serves as a basis for preparedness for non-conventional events. Coping with chemical casualties necessitates decontamination of casualties, treating victims with acute stress reactions, expanding surge capacities of hospitals, and integrating knowledge through drills. Risk communication also is important. ASSESSMENT OF EMERGENCY PREPAREDNESS: An annual assessment of the emergency plan is required in order to assure emergency preparedness. Preparedness assessments should include: (1) elements of disaster planning; (2) emergency coordination; (3) communication; (4) training; (5) expansion of hospital surge capacity; (6) personnel; (7) availability of equipment; (8) stockpiles of medical supplies; and (9) expansion of laboratory capacities. The assessment program must be based on valid criteria that are measurable, reliable, and enable conclusions to be drawn. There are several assessment tools that can be used, including surveys, parameters, capabilities evaluation, and self-assessment tools. SUMMARY: Healthcare systems are required to prepare an effective response model to cope with MCIs. Planning should be envisioned as a process rather than a production of a tangible product. Assuring emergency preparedness requires a structured methodology that will enable an objective assessment of the level of readiness. PMID- 17334196 TI - Casualty collection in mass-casualty incidents: a better method for finding proverbial needles in a haystack. AB - INTRODUCTION: Mass-casualty incidents (MCIs) are on the rise. The ability to locate, identify, and triage patients quickly and efficiently results in better patient outcomes. Poor lighting due to time of day, inclement weather, and power outages can make locating patients difficult. Efficient methods of locating patients allow for quicker transport to definitive care. OBJECTIVE: The objective of this study was to evaluate the methods currently used in mass-casualty collection, and to determine whether the use of the Simple Triage and Rapid Treatment (START) triage tag system can be improved by using easily discernable tags (glow sticks) in conjunction with the standard triage tags. METHODS: Numerous drills were performed utilizing the START triage method. In Trial A, patients were identified with the triage tags only. In Trial B, patients were identified using triage tags and glow sticks. Four rounds of triage drills were performed in low ambient light for each Trial, and the differences in casualty collection times were compared. RESULTS: Casualty relocation and collection times were considerably shorter in the trials that utilized both the glow sticks and triage tags. An average of 2.58 minutes (31.75%) were saved during the casualty collections. In addition, fewer patient errors occurred during the trials in which the glow sticks were used. Between the four rounds, an average of four patient errors occurred during the trials that utilized the triage tags. However, there was an average of only one patient error for the drills when participants utilized both the triage tags and the glow sticks. CONCLUSIONS: The use of the highly visible glow sticks, in conjunction with the START triage tags, allowed for more rapid and accurate casualty collection in suboptimal lighting. The use of the glow sticks made it easier to relocate previously triaged patients and arrange for expeditious transport to definitive care. In addition, the glow sticks reduced the number of patient errors. Most importantly, there was a significant reduction in the number of patients that initially were triaged via the START method, but were overlooked during casualty collection and transport. PMID- 17334197 TI - Mental illness is not the same as incompetence: voting rights, archaic laws, & stigmatizing language. PMID- 17334199 TI - Can we immunize children against violence? AB - Psychiatric nurses should support best practices to prevent youth violence. The magnitude and significance of youth violence gives us both social and moral mandates to proceed. Health care professionals have made giant strides in sparing our children from the ravages of childhood diseases. Let us try to do the same by preventing the development of violent behaviors. PMID- 17334198 TI - Managing common Side effects of SSRIs. PMID- 17334200 TI - Living with type 2 diabetes: marital perspectives of middle-aged and older couples. AB - Type 2 diabetes is a significant health problem among middle-aged and older adults in the United States. Given the life-altering nature of this condition, examination of the psychosocial context in which people with diabetes live may enhance long-term diabetic care. This qualitative study aimed to understand the similarities and differences in spouses' beliefs about diabetes, the perceived effects on daily life, and the management of diabetes in the context of marriage. Data analysis revealed three themes: vulnerability, burden, and getting by. This descriptive study provides a unique perspective on couples' beliefs about diabetes, which have important implications for the nursing community in acknowledging spousal beliefs in the management of diabetes. PMID- 17334201 TI - A recovery-oriented approach to psychiatric medication: guidelines for nurses. AB - Despite the well-documented effectiveness of psychiatric medication, studies reveal that it is used by only approximately half of those for whom it is prescribed. Whereas large-scale studies have focused primarily on the consequences of not taking medication as prescribed, a number of recent qualitative studies have tried to understand the phenomenon from the perspective of consumers. Findings have revealed that nonadherence may not always reflect psychopathology or a lack of insight, but rather a personal choice directed toward engaging in activities that provide meaning and purpose. In this article, we review the literature on medication use, emphasizing the importance of the practitioner-consumer relationship. We also present a recovery-oriented perspective to understand consumers' choices regarding medication use and discuss practical guidelines for psychiatric nurses. PMID- 17334202 TI - Eagle soaring: the power of the resilient self. AB - Adversity can be an opportunity to focus on strengths and nurture resiliency. Cultural understanding and awareness can be easily incorporated into therapy through empathic listening, a therapeutic alliance, and supportive understanding. Patients should not subscribe to "victim" labels. Resilience should be celebrated. PMID- 17334203 TI - Working memory in the brain. PMID- 17334204 TI - Binding of what and where during working memory maintenance. AB - Prefrontal cortex (PFC) supports the maintenance of currently relevant information in working memory (WM). How the PFC is organized for the maintenance of disparate information, how this information is conjoined into a unified whole, and how the representation may change with task demands is still debated. The pattern of neural activity during maintenance of either abstract visual patterns, locations, or their "conjunction" was measured in two experiments using functional magnetic resonance imaging (fMRI). During delays, common regions in PFC were active, but a dorsal-ventral/spatial-nonspatial functional topography distinguished among the three delay types. During conjunction delays, no additional neural architecture was recruited. Instead, conjunction delays were characterized by a significant reduction compared to the response of that cortical region while maintaining its "preferred" information. A model is presented, extending the principles of "biased competition" to the PFC and the dynamic maintenance of information in WM, that accounts for current and seemingly contradictory previous results from both imaging and physiological studies. In this schema, the PFC is not only the source of biasing signals targeting earlier processing regions, but is also the target of these signals. This model stands as an alternative to traditional "domain specific" and "domain general" models of frontal organization of WM, and as an extension of earlier models of PFC mechanisms related to the cognitive control of goal directed behavior. PMID- 17334205 TI - Sustained and transient neural modulations in prefrontal cortex related to declarative long-term memory, working memory, and attention. AB - Common activations in prefrontal cortex (PFC) during episodic and semantic long term memory (LTM) tasks have been hypothesized to reflect functional overlap in terms of working memory (WM) and cognitive control. To evaluate a WM account of LTM-general activations, the present study took into consideration that cognitive task performance depends on the dynamic operation of multiple component processes, some of which are stimulus-synchronous and transient in nature; and some that are engaged throughout a task in a sustained fashion. PFC and WM may be implicated in both of these temporally independent components. To elucidate these possibilities we employed mixed blocked/event-related functional magnetic resonance imaging (fMRI) procedures to assess the extent to which sustained or transient activation patterns overlapped across tasks indexing episodic and semantic LTM, attention (ATT), and WM. Within PFC, ventrolateral and medial areas exhibited sustained activity across all tasks, whereas more anterior regions including right frontopolar cortex were commonly engaged in sustained processing during the three memory tasks. These findings do not support a WM account of sustained frontal responses during LTM tasks, but instead suggest that the pattern that was common to all tasks reflects general attentional set/vigilance, and that the shared WM-LTM pattern mediates control processes related to upholding task set. Transient responses during the three memory tasks were assessed relative to ATT to isolate item-specific mnemonic processes and were found to be largely distinct from sustained effects. Task-specific effects were observed for each memory task. In addition, a common item response for all memory tasks involved left dorsolateral PFC (DLPFC). The latter response might be seen as reflecting WM processes during LTM retrieval. Thus, our findings suggest that a WM account of shared PFC recruitment in LTM tasks holds for common transient item-related responses rather than sustained state-related responses that are better seen as reflecting more general attentional/control processes. PMID- 17334206 TI - Relationship between prefrontal task-related activity and information flow during spatial working memory performance. AB - While monkeys performed spatial working memory tasks, cue- (C), delay- (D), and response-period (R) activities or their combinations (CD, CR, DR, CDR) were observed in prefrontal neurons. In the present study, we tried to understand information flow during spatial working memory performances and how each task related neuron contributed to this process. We first characterized each neuron based on which task-related activity was exhibited and which information (cue location or saccade direction) each task-related activity represented, then classified these neurons into 9 groups (C, Dcue, Dsac, CDcue, DcueRcue, DsacRsac, DcueRsac, CDcueRcue and CDcueRsac). Preferred directions were similar between cue and delay-period activities in CDcue, CDcueRcue, and CDcueRsac, indicating that the directional selectivity of delay-period activity is affected by the directional selectivity of cue-period activity, all of which represented visual information. Preferred directions were also similar between delay- and response period activities in DcueRcue, CDcueRcue, and DsacRsac, indicating that the directional selectivity of delay-period activity affects the directional selectivity of response-period activity in these neurons. By the comparison of temporal profiles of delay-period activity among these groups, we found (1) cue period activity could affect directional selectivity of delay-period activity of CDcue and CDcueRcue, (2) cue-period activity of C, CDcue, and CDcueRcue might contribute to the initiation and the maintenance of delay-period activity of CDcue, CDcueRcue, Dcue, and DcueRcue, and (3) saccade-related activity of DsacRsac could be affected by delay-period activity of Dsac and DsacRsac. These results suggest that the combination of task-related activities, the information represented by each activity, and the temporal profile of delay-period activity are important factors to consider information flow and processing and integration of the information in the prefrontal cortex during spatial working memory processes. PMID- 17334207 TI - Reward expectancy-related prefrontal neuronal activities: are they neural substrates of "affective" working memory? AB - Primate prefrontal delay neurons are involved in retaining task-relevant cognitive information in working memory (WM). Recent studies have also revealed primate prefrontal delay neurons that are related to reward/omission-of-reward expectancy. Such reward-related delay activities might constitute "affective WM" (Davidson, 2002). "Affective" and "cognitive" WM are both concerned with representing not what is currently being presented, but rather what was presented previously or might be presented in the future. However, according to the original and widely accepted definition, WM is the "temporary storage and manipulation of information for complex cognitive tasks". Reward/omission-of reward expectancy-related neuronal activity is neither prerequisite nor essential for accurate task performance; thus, such activity is not considered to comprise the neural substrates of WM. Also, "affective WM" might not be an appropriate usage of the term "WM". We propose that WM- and reward/omission-of-reward expectancy-related neuronal activity are concerned with representing which response should be performed in order to attain a goal (reward) and the goal of the response, respectively. We further suggest that the prefrontal cortex (PFC) plays a crucial role in the integration of cognitive (for example, WM-related) and motivational (for example, reward expectancy-related) operations for goal directed behaviour. The PFC could then send this integrated information to other brain areas to control the behaviour. PMID- 17334208 TI - Age-related differences in activation-performance relations in delayed-response tasks: a multiple component analysis. AB - We used event-related functional magnetic resonance imaging (fMRI) to measure prefrontal cortex (PFC) activity while younger and older adults performed an item recognition task in which the memory-set size varied between 1 and 8 letters. Each trial was composed of a 4-sec encoding period in which subjects viewed random letter strings, a 12-sec retention period and a 2-sec retrieval period in which subjects decided whether a single probe letter was or was not part of the memory set. For both groups, reaction-time (RT) increased and accuracy decreased with increasing memory set-size. Analyses of individual subjects' performance and cortical activity indicated that speed and accuracy accounted for variance in different task periods in dorsal and ventral PFC. Age-related differences in accuracy-activation relations were observed in dorsal PFC during encoding and ventral PFC during maintenance. Age-related differences in RT-activation relations were observed in dorsal PFC during retrieval. These results and additional fMRI data we have collected during performance of a speeded processing task, directly support a model of cognitive slowing in which processing rate is related to neural efficiency. PMID- 17334209 TI - Electrophysiological measures of maintaining representations in visual working memory. AB - Visual working memory (WM) is a limited capacity system which maintains information about objects in the immediate visual environment. Recent neurophysiological and neuroimaging studies have identified sustained memory-item specific activity during the retention period of WM tasks, and this activity may be a physiological substrate of maintaining representations in WM. In the present study, we present an electrophysiological measure of delay activity using event related potentials (ERPs). Subjects were asked to remember the items in a single hemifield presented within a bilateral display. Approximately 200 msec following the onset of the memory array, we observed a large negative wave at electrode sites that were contralateral with respect to the position of the memory items. This activity persisted throughout the retention period and appears to be an analog to delay activity observed in monkey single-unit and functional magnetic resonance imaging (fMRI) WM studies. The contralateral delay activity is modulated by the number of items in the memory array but reaches asymptote for arrays of 3 to 4 items. This activity is similar across different classes of simple objects and the amplitude is smaller on incorrect response trials relative to correct trials, suggesting that this activity is necessary for correct performance on a given trial. Together, these results appear to indicate an electrophysiological index of the maintained representations in visual WM. PMID- 17334210 TI - Working memory brain activation following severe traumatic brain injury. AB - Functional magnetic resonance imaging (fMRI) has shown that brain activation during performance of working memory (WM) tasks under high memory loads is altered in adults with severe traumatic brain injury (TBI) relative to uninjured subjects (Perlstein et al., 2004; Scheibel et al., 2003). Our study attempted to equate TBI patients and orthopedically injured (OI) subjects on performance of an N-Back task that used faces as stimuli. To minimize confusion in TBI patients that was revealed in pilot work, we presented the memory conditions in two separate tasks, 0- versus 1-back and 0- versus 2-back. In the 0- versus 1-back task, OI subjects activated bilateral frontal areas more extensively than TBI patients, and TBI patients activated posterior regions more extensively than OI subjects. In the 0- versus 2-back task, there were no significant differences between the groups. Analysis of changes in activation over time on 1-back disclosed that OI subjects had decreases in bilateral anterior and posterior regions, while TBI patients showed activation increases in those and other areas over time. In the 2-back condition, both groups showed decreases over time in fusiform and parahippocampal gyri, although the OI group also showed increases over time in frontal, parietal, and temporal areas not seen in the TBI patients. The greatest group differences were found in the 1-back condition, which places low demand on WM. Although the extent of activation in the 2-back condition did not differ between the two groups, deactivation in the 2-back condition was seen in the OI patients only, and both groups' patterns of activation over time varied, suggesting a dissociation between the TBI and OI patients in recruitment of neural areas mediating WM. PMID- 17334211 TI - Proactive interference in a semantic short-term memory deficit: role of semantic and phonological relatedness. AB - Previous research has indicated that patients with semantic short-term memory (STM) deficits demonstrate unusual intrusions of previously presented material during serial recall tasks (Martin and Lesch, 1996). These intrusions suggest excessive proactive interference (PI) from previous lists. Here, we explore one such patient's susceptibility to PI. Experiment 1 demonstrated patient M.L.'s extreme susceptibility to PI using a probe recognition task that manipulates the recency of negative probes (the recent negatives task). When stimuli consisted of letters, M.L. showed greatly exaggerated effects of PI, well outside of the range of healthy control participants. Experiment 2 used a variation of the recent negatives task to examine the relative contribution of semantic and phonological relatedness in PI. This task manipulated semantic and phonological relatedness of probes and recently presented list items. Relative to healthy control participants, patient M.L. showed exaggerated interference effects for both phonological and semantically related probes, both for probes related to the current list and for probes related to the previous list. These data have important implications for theories of semantic STM deficits. Specifically, these data suggest that it is not the rapid decay of semantic representations that is responsible for difficulties in short-term recall, but rather the abnormal persistence of previously presented material. We propose that this susceptibility to PI is the result of a deficit in control processes acting on STM. PMID- 17334212 TI - From dichotic listening to the irrelevant sound effect: a behavioural and neuroimaging analysis of the processing of unattended speech. AB - The assumption that ignoring irrelevant sound in a serial recall situation is identical to ignoring a non-target channel in dichotic listening is challenged. Dichotic listening is open to moderating effects of working memory capacity (Conway et al., 2001) whereas irrelevant sound effects (ISE) are not (Beaman, 2004). A right ear processing bias is apparent in dichotic listening, whereas the bias is to the left ear in the ISE (Hadlington et al., 2004). Positron emission tomography (PET) imaging data (Scott et al., 2004, submitted) show bilateral activation of the superior temporal gyrus (STG) in the presence of intelligible, but ignored, background speech and right hemisphere activation of the STG in the presence of unintelligible background speech. It is suggested that the right STG may be involved in the ISE and a particularly strong left ear effect might occur because of the contralateral connections in audition. It is further suggested that left STG activity is associated with dichotic listening effects and may be influenced by working memory span capacity. The relationship of this functional and neuroanatomical model to known neural correlates of working memory is considered. PMID- 17334213 TI - Refreshing: a minimal executive function. AB - Executive functions include processes by which important information (e.g., words, objects, task goals, contextual information) generated via perception or thought can be foregrounded and thereby influence current and subsequent processing. One simple executive process that has the effect of foregrounding information is refreshing--thinking briefly of a just-activated representation. Previous studies (e.g., Johnson et al., 2005) identified refresh-related activity in several areas of left prefrontal cortex (PFC). To further specify the respective functions of these PFC areas in refreshing, in Experiment 1, healthy young adult participants were randomly cued to think of a just previously seen word (refresh) or cued to press a button (act). Compared to simply reading a word, refresh and act conditions resulted in similar levels of activity in left lateral anterior PFC but only refreshing resulted in greater activity in left dorsolateral PFC. In Experiment 2, refreshing was contrasted with a minimal phonological rehearsal condition. Refreshing was associated with activity in left dorsolateral PFC and rehearsing with activity in left ventrolateral PFC. In both experiments, correlations of activity among brain areas suggest different functional connectivity for these processes. Together, these findings provide evidence that (1) left lateral anterior PFC is associated with initiating a non automatic process, (2) left dorsolateral PFC is associated with foregrounding a specific mental representation, and (3) refreshing and rehearsing are neurally distinguishable processes. PMID- 17334214 TI - Mapping the updating process: common and specific brain activations across different versions of the running span task. AB - Neuroimaging studies exploring the neural substrates of executive functioning have only rarely investigated whether the non-executive characteristics of the experimental executive tasks could contribute to the observed brain activations. The aim of this study was to determine cerebral activity in three different tasks involving the updating executive function. The experimental updating tasks required subjects to process strings of items (respectively letters, words, and sounds) of unknown lengths, and then to recall or identify a specific number of presented items. Conjunction and functional connectivity analyses demonstrated that the cerebral areas activated by all three experimental tasks are the left frontopolar cortex, bilateral dorsolateral prefrontal and premotor cortex, bilateral intraparietal sulcus, right inferior parietal lobule and cerebellum. Some regions of this network appear to be more specific to each updating task. These results clearly indicate that the neural substrates underlying a specific executive process (in this case, updating) are modulated by the exact requirements of the task (such as the material to process or the kind of response) and the specific cognitive processes associated with updating. PMID- 17334215 TI - Dual task demands on encoding and retrieval processes: evidence from healthy adult ageing. AB - Previous studies of dual-task performance have demonstrated that encoding and retrieval processes are differentially affected by the simultaneous performance of a secondary task. Whilst dual task demands during encoding have a detrimental effect on memory performance, dual task demands during retrieval have a detrimental effect on secondary task performance. However, dual task effects on memory during encoding appear unaffected by age, while effects at retrieval on secondary task performance are age sensitive. Most previous studies have focused on free recall or cued recall of word lists. In the current study, encoding and retrieval were examined in younger and older healthy adults performing a task typically thought to load verbal working memory, namely immediate serial ordered digit recall together with a response time (RT) task. In Experiment 1, the demands of a secondary RT task were varied as a function of response-to-stimulus interval, while in Experiment 2 the predictability of the stimulus location was manipulated. In both age groups, dual task during encoding, but not at retrieval, produced significant interference in memory performance and unlike most previous studies the impact at encoding was greater for the older group. In contrast, significantly slower RTs were demonstrated under dual task conditions during encoding and retrieval. Older adults produced significantly slower RTs than younger adults only for dual task at retrieval. Older people were more sensitive to time pressure in responding under dual task conditions, but neither group was sensitive to predictability of stimulus location. Results are consistent with the concept of a cognitive resource that supports dual task performance, and that is sensitive to the effects of age on memory encoding of items that rely heavily on the operation of verbal working memory resources. The age sensitivity to dual task only became apparent when effects at encoding and at retrieval were considered separately. PMID- 17334216 TI - New IHI campaign will target medical harm in U.S. hospitals. AB - Volunteer "nodes" and mentor facilities will offer guidance to participating hospitals. "Getting boards on board" may be most challenging of six new initiatives. Measurement of complications may be more difficult than measurement of mortality. PMID- 17334217 TI - Rural facility receives Baldrige for 2006. AB - Facility adopts a "no-secrets, no-excuses, open communication environment." Care based management another key strategy that sets facility apart. New PI ideas that prove effective in one department are quickly disseminated to rest of facility. PMID- 17334218 TI - Hospitals collaborate on i.v. meds standards. AB - Task force pares down 85 different concentrations, 57 different dosage units for 34 IV medications. Different dosages, concentrations create huge opportunities for errors. Program taking hold, garnering attention of national organizations. PMID- 17334219 TI - Private sector P4P taking hold, expert says. AB - Data have yet to prove that change has occurred as a result of P4P programs. Unanswered questions include, How much reward is necessary to produce results? More data, more experience needed for P4P to achieve its full potential. PMID- 17334220 TI - CMS to publicly report hospital mortality rates. AB - Data will be risk-adjusted, using mortality rates 30 days after discharge. CMS has begun "previewing" data with hospitals to help familiarize them with new format. Additional data may help hospitals put previous "negative" performance reports in perspective. PMID- 17334221 TI - Multivariable testing cuts door-to-doc times by 24%. PMID- 17334223 TI - A human mutant CD4 molecule resistant to HIV-1 binding restores helper T lymphocyte functions in murine CD4-deficient mice. AB - CD4 is a cell surface glycoprotein that acts as a co-receptor for the T cell antigen receptor by binding to a non-polymorphic portion of MHC molecules. CD4 also functions as a receptor for human immunodeficiency virus type-I (HIV-1) because the viral envelope glycoprotein gp120 binds to CD4 with a high affinity. We have previously demonstrated that introduction of mutations into CD4 abolished the binding of gp120 and prevented HIV-1 from entering cells and spreading. However, whether introduction of such mutations into CD4 causes decreased binding to MHC and loss of function is yet to be determined. We generated transgenic mouse lines by injecting a mutant human CD4 (muthCD4) gene under a murine CD4 enhancer/promoter to ensure tissue and stage specific expression. To exclude the influence of endogenous murine CD4, transgenic mice were crossed with murine CD4 targeted mice to produce muthCD4 transgenic mice lacking endogenous CD4 (muthCD4TG/KO mice). In these mice, T lymphocytes expressing muthCD4 expanded and matured in the thymus and were present in the spleen and lymph nodes. They also activated B cells to mount an antibody response to a T-dependent antigen. The results from this study suggest that a human variant of CD4 modified to be resistant to HIV-1 binding can rescue the signaling for T cell development in the thymus in vivo, having helper T cell functions. Thus, further characterization of muthCD4 molecules should open the way to new HIV treatment modalities. PMID- 17334224 TI - SIRT1 promotes DNA repair activity and deacetylation of Ku70. AB - Human SIRT1 controls various physiological responses including cell fate, stress, and aging, through deacetylation of its specific substrate protein. In processing DNA damage signaling, SIRT1 attenuates a cellular apoptotic response by deacetylation of p53 tumor suppressor. The present study shows that, upon exposure to radiation, SIRT1 could enhance DNA repair capacity and deacetylation of repair protein Ku70. Ectopically over-expressed SIRT1 resulted in the increase of repair of DNA strand breakages produced by radiation. On the other hand, repression of endogenous SIRT1 expression by SIRT1 siRNA led to the decrease of this repair activity, indicating that SIRT1 can regulate DNA repair capacity of cells with DNA strand breaks. In addition, we found that SIRT1 physically complexed with repair protein Ku70, leading to subsequent deacetylation. The dominant-negative SIRT1, a catalytically inactive form, did not induce deacetylation of Ku70 protein as well as increase of DNA repair capacity. These observations suggest that SIRT1 modulates DNA repair activity, which could be regulated by the acetylation status of repair protein Ku70 following DNA damage. PMID- 17334225 TI - Neuronal loss in primary long-term cortical culture involves neurodegeneration like cell death via calpain and p35 processing, but not developmental apoptosis or aging. AB - Primary neuronal culture is a powerful tool to study neuronal development, aging, and degeneration. However, cultured neurons show signs of cell death after 2 or 3 weeks. Although the mechanism underlying this phenomenon has not been elucidated, several preventive methods have been identified. Here we show that the neuronal loss in primary cortical culture involves calpain activation and subsequent neuronal cell death. Neuronal loss during cultivation showed destruction of neurites and synapses, and a decrease in neuron numbers. mu-Calpain and m-calpain were initially activated and accumulated by increased RNA expression. This neuronal death exhibited neurodegenerative features, such as conversion of p35 to p25, which is important in the developmental process and in the pathogenesis of Alzheimer's disease. But, postnatal and aged rat cortex did not show calpain activation and prolonged processing of p35 to p25, in contrast to the long-term culture of cortical neurons. In addition, the inhibition of calpains by ALLM or ALLN blocked the conversion of p35 to p25, indicating that the calpain activity is essential for the neurodegenerative features of cell death. Taken together, this study shows that the neuronal loss in primary cortical cultures involves neurodegeneration-like cell death through the activation of calpains and the subsequent processing of p35 to p25, but not developmental apoptosis or aging. Our results suggest that the long term primary culture of cortical neurons represent a valuable model of neurodegeneration, such as Alzheimer's disease. PMID- 17334226 TI - Extracellular HIV-1 Tat enhances monocyte adhesion by up-regulation of ICAM-1 and VCAM-1 gene expression via ROS-dependent NF-kappaB activation in astrocytes. AB - One of characteristic features of AIDS-related encephalitis and dementia is the infiltration of monocytes into the CNS. HIV-1 Tat was demonstrated to facilitate monocyte entry into the CNS. In this study, we examined the effect of HIV-1 Tat on the expression of adhesion molecules, generation of reactive oxygen species (ROS) and NF-kappaB activation in CRT-MG human astroglioma cells. Treatment of CRT-MG cells with HIV-1 Tat protein significantly increased protein and mRNA levels of ICAM-1 and VCAM-1, as measured by Western blot analysis and RT-PCR, indicating that Tat increases these protein levels at an mRNA level. In addition, Tat induced the activation of NF-kappaB in astrocytes. Treatment of CRT-MG with NF-kappaB inhibitors led to decrease in Tat-induced protein and mRNA expression of ICAM-1 and VCAM-1. Furthermore, HIV-1 Tat protein increased ROS generation. Inhibition of Tat-induced ROS generation by N-acetyl cysteine, vitamin C and diphenyl iodonium suppressed Tat-induced NF-kappaB activation, ICAM-1 and VCAM-1 expression, and monocyte adhesion in CRT-MG. These data indicate that HIV-1 Tat can modulate monocyte adhesiveness by increasing expression of adhesion molecules such as ICAM-1 and VCAM-1 via ROS- and NF-kappaB-dependent mechanisms in astrocytes. PMID- 17334227 TI - Heat shock protein 70 alters the endosome-lysosomal localization of huntingtin. AB - Huntington's disease is caused by CAG trinucleotide expansions in the gene encoding huntingtin. N- terminal fragments of huntingtin with polyglutamine produce aggregates in the endosome-lysosomal system, where proteolytic fragments of huntingtin is generated. Heat shock protein 70 (HSP70) prevents the formation of protein aggregates, but the effect of HSP70 on the huntingtin in the endosome lysosomal system is unknown. This study was to determine whether HSP70 alters the distribution of huntingtin in endosome-lysosomal system. HSP70 expressing stable cells (NIH/3T3 or cerebral hybrid cell line A1) were generated, and mutant [(CAG)(100)] huntingtin was transiently overexpressed. Analysis of subcellular distribution by immunocytochemistry or proteolysis cleavage by Western blotting was performed. 18 CAG repeat wild type [WT; (CAG)(18)] huntingtin was used as a control. Cells with huntingtin showed patterns of endosome-lysosomal accumulation, from a "dispersed vacuole (DV)" type into a coalescent "perinuclear vacuole (PV)" type over time. In WT huntingtin, HSP70 increased the cells with the PV types that enhanced the proteolytic cleavage of huntingtin. However, HSP70 reduced cells of the DV and PV types expressing mutant huntingtin, that result in less proteolysis than that of control. In addition, intranuclear inclusions were formed only in mutant cells, which was not affected by HSP70. These results suggest that HSP70 alters the distribution of huntingtin in the endosome- lysosomal system, and that this contributes to huntingtin proteolysis. PMID- 17334228 TI - Psammaplin A is a natural prodrug that inhibits class I histone deacetylase. AB - Histone deacetylase (HDAC) has been highlighted as one of key players in tumorigenesis and angiogenesis. Recently, several derivatives of psammaplin (Psams) from a marine sponge have been known to inhibit the HDAC activity, but the molecular mechanism for the inhibition has not fully understood. Here, we explored the mode of action of Psams for the inhibition of HDAC activity in the molecular and cellular level. Among the derivatives, psammaplin A (Psam A) showed the potent inhibitory activity in enzyme assay and anti-proliferation assay with IC50 value of 0.003 and 1 muM, respectively. Psam A selectively induced hyperacetylation of histones in the cells, resulting in the upregulation of gelsolin, a well-known HDAC target gene, in a transcriptional level. In addition, reduced Psam A showed a stronger inhibitory activity than that of non-reduced one. Notably, glutathione-depleted cells were not sensitive to Psam A, implying that cellular reduction of the compound is responsible for the HDAC inhibition of Psam A after uptake into the cells. Together, these data demonstrate that Psam A could exhibit its activity under the reduced condition in the cells and be a new natural prodrug targeting HDAC. PMID- 17334229 TI - STP-A11, an oncoprotein of Herpesvirus saimiri augments both NF-kappaB and AP-1 transcription activity through TRAF6. AB - Herpesvirus saimiri (HVS), a member of the gamma-herpesvirus family, encodes an oncoprotein called Saimiri Transforming Protein (STP) which is required for lymphoma induction in non-human primates. However, a detailed mechanism of STP A11-induced oncogenesis has not been revealed yet. We first report that STP-A11 oncoprotein interacts with TNF-alpha receptor-associated factor (TRAF) 6 in vivo and in vitro. Mutagenesis analysis of the TRAF6-binding motif (10)PQENDE(15) in STP-A11 reveals that Glu (E)(12) residue is critical for binding to TRAF6 and NF kappaB activation. Interestingly, co-expression of E12A mutant, lack of TRAF6 binding, with cellular Src (Src) results in decreased transcriptional activity of Stat3 and AP-1, a novel target of STP-A11 compared to that of wild type. Furthermore, the presence of STP-A11 enhances the association of TRAF6 with Src and induces the translocation of both TRAF6 and Src to a nonionic detergent insoluble fraction. Taken together, these studies suggest that STP-A11 oncoprotein up-regulates both NF-kappaB and AP-1 transcription activity through TRAF6, which would ultimately contribute cellular transformation. PMID- 17334230 TI - Sodium tanshinone IIA sulfonate depresses angiotensin II-induced cardiomyocyte hypertrophy through MEK/ERK pathway. AB - Cardiomyocyte hypertrophy is a major cause of morbidity and mortality worldwide. The aim of this study is to determine the effects of sodium tanshinone IIA sulfonate (STS) on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) in vivo and in vitro. In long-term treatment, adult Wistar rats were infused with Ang II for three weeks via osmotic mini-pumps and some of them were given intragastrically of STS. Left ventricle was isolated; the ratio of left ventricular weight to body weight and systolic blood pressure (SBP) were determined and heart morphometry was assessed after hematoxylin and eosin staining. Results indicated STS inhibited Ang II-induced increases in myocyte diameter and decreased the LVW/BW ratio independent of decreasing systolic blood pressure. In vitro, treatment of cultured cardiomyocytes with STS inhibited Ang II-induced increase in cell size, protein synthesis, ANP expression, activation of extracellular signal- regulated kinase (ERK) and ERK kinase (MEK). Then we reexamined the mechanism of STS-induced anti-hypertrophic effects. Results revealed MEK inhibitor U0126 (20 microM) markedly enhanced STS-induced depressions in [(3)H]leucine incorporation and ANP expression. In conclusion, MEK/ERK pathway plays a significant role in the anti-hypertrophic effects of STS. PMID- 17334231 TI - Tyrosine nitration site specificity identified by LC/MS in nitrite-modified collagen type IV. AB - Non-enzymatic nitrite induced collagen cross-linking results in changes reminiscent of age-related damage and parallels the well-known model system, non enzymatic glycation. We have recently observed that nitrite modification of basement membrane proteins can induce deleterious effects on overlying retinal pigment epithelial cells in studies relevant to age-related macular degeneration. The present work was undertaken in order to confirm 3-nitro-tyrosine (3-NT) as a product of the reaction and to identify the site specificity of nitration in collagen IV, a major component of basement membranes. Human collagen type IV was modified via incubation with 200 mM NaNO(2) (pH=7.38) for one week at 37(o)C. The modified protein was prepared in 2 different ways, including acid hydrolysis and trypsin digestion for site specificity determination. The samples were analyzed by LC/MS using a C(12) RP column. Site specificity was determined from tandem MS/MS data utilizing TurboSEQUEST software and the Swiss-Prot sequence database. 3-NT was detected in protein digests and acid hydrolysates of nitrite modified collagen IV. Positive identification with standard 3-NT was confirmed by identical R(t), lambda(max)=279 nm and 355 nm, and m/z=227. Analyses of tryptic digests identified four sites of tyrosine nitration, alpha1(IV)Y348, alpha1(IV)Y534, alpha2(IV)Y327, and alpha2(IV)Y1081. These sites are located in the triple-helical region of the protein and provide clues regarding potential sites for nitrite modification in collagen type IV. PMID- 17334232 TI - Coordinated change of a ratio of methylated H3-lysine 4 or acetylated H3 to acetylated H4 and DNA methylation is associated with tissue-specific gene expression in cloned pig. AB - Various cell types in higher multicellular organisms are genetically homogenous, but are functionally and morphologically heterogeneous due to the differential expression of genes during development, which appears to be controlled by epigenetic mechanisms. However, the exact molecular mechanisms that govern the tissue-specific gene expression are poorly understood. Here, we show that dynamic changes in histone modifications and DNA methylation in the upstream coding region of a gene containing the transcription initiation site determine the tissue-specific gene expression pattern. The tissue-specific expression of the transgene correlated with DNA demethylation at specific CpG sites as well as significant changes in histone modifications from a low ratio of methylated H3- lysine 4 or acetylated H3-lysine 9, 14 to acetylated H4 to higher ratios. Based on the programmed status of transgene silenced in cloned mammalian ear-derived fibroblasts, the transgene could be reprogrammed by change of histone modification and DNA methylation by inhibiting both histone deacetylase and DNA methylation, resulting in high expression of the transgene. These findings indicate that dynamic change of histone modification and DNA methylation is potentially important in the establishment and maintenance of tissue-specific gene expression. PMID- 17334233 TI - PMA-induced up-regulation of MMP-9 is regulated by a PKCalpha-NF-kappaB cascade in human lung epithelial cells. AB - Expression of matrix metalloproteinase-9 (MMP-9) is associated with airway remodeling and tissue injury in asthma. However, little is known about how MMP-9 is up-regulated in airway epithelial cells. In this study, we show that phorbol myristate acetate (PMA) induces MMP-9 expression via a protein kinase Calpha (PKCalpha)-dependent signaling cascade in BEAS-2B human lung epithelial cells. Pretreatment with either GF109203X, a general PKC inhibitor, or Go6976, a PKCalpha/beta isozyme inhibitor, inhibited PMA-induced activation of the MMP-9 promoter, as did transient transfection with PKCalpha antisense oligonuclotides. PMA activated NF-kappaB by phosphorylating IkappaB in these cells and this was also inhibited by GF109203X and Go6976, suggesting that PKCa acts as an upstream regulator of NF-kappaB in PMA-induced MMP-9 induction. Our results indicate that a "PKCalpha-NF- kappaB"-dependent cascade is involved in the signaling leading to PMA-induced MMP-9 expression in the lung epithelium. PMID- 17334234 TI - Alpha-lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF kappaB transcriptional activity. AB - The migration of vascular smooth muscle cells (VSMCs) into the intima, an important step in injury-induced neointimal hyperplasia, requires the activation of nuclear factor-kappaB (NF-kappaB) and the consequent up-regulation of matrix metalloproteinase-9 (MMP-9). This study was undertaken to test for a possible effect of alpha-lipoic acid (ALA), a potent inhibitor of NF-kappaB, on MMP-9 expression. ALA inhibited high-glucose- and TNF-alpha-stimulated VSMC migrations in vitro. It also inhibited high-glucose- and TNF-alpha-induced increases in MMP 9 expression. The activity of MMP-9-promoter constructs with mutations in the NF kappaB binding site was not inhibited by ALA, indicating an involvement of the NF kappaB signaling pathway in the ALA-specific inhibition of MMP-9. These data suggest the possibility that ALA may be useful for the prevention of neointimal hyperplasia after angioplasty, by inhibiting the NF-kappaB/MMP-9 pathway, especially with hyperglycemia. PMID- 17334235 TI - Lamin A/C mutations associated with familial and sporadic cases of dilated cardiomyopathy in Koreans. AB - Dilated cardiomyopathy (DCM) is characterized by cardiac dilation and systolic dysfunction. So far sixteen genes have been shown to cause autosomal dominant familial dilated cardiomyopathy (FDC). We identified a large Korean family from the Jeju island showing a clear Mendelian inheritance of FDC. A genomewide linkage scan at 9 cM marker density identified a peak multipoint LOD score of 2.82 at D1S195. Haplotyping of the region with 15 additional markers defined a candidate interval that included a known candidate gene encoding the lamin A/C (LMNA). Sequencing of the LMNA exons revealed one missense mutation at C568T (Arg190Trp) in the alpha-helical rod domain of the LMNA gene co-segregating with FDC with conduction-system disease. The same mutation was found in patients of another Korean family with FDC without conduction-system disease. Upon screening 14 sporadic DCM cases, we found three LMNA mutations including a case having a previously described (Glu161Lys) mutation and two having novel mutations (Glu53Val and Glu186Lys). Our results suggest that variable genotypes of laminopathy are implicated in not only familial but also considerable proportion of sporadic DCM. PMID- 17334236 TI - TNF-alpha upregulates PTEN via NF-kappaB signaling pathways in human leukemic cells. AB - TNF-alpha plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between the two molecules are suggested. TNF-alpha has been known to downregulate PTEN via NF-kappaB pathway in the human colon cell line, HT-29. However, here we show the opposite finding that TNF-alpha upregulates PTEN via activation of NF kappaB in human leukemic cells. TNF-alpha increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of NF-kappaB with p65 antisense phosphorothioate oligonucleotide or pyrrolidine dithiocarbamate. We found that TNF-alpha activated the NF-kappaB pathways, evidenced by the translocation of p65 to the nucleus in TNF-alpha treated cells. We conclude that TNF-alpha induces upregulation of PTEN expression through NF-kappaB activation in human leukemic cells. PMID- 17334237 TI - Interleukin-1 mediates thermal injury-induced lung damage through C-Jun NH2 terminal kinase signaling. AB - OBJECTIVE: The molecular mechanisms of lung damage following thermal injury are not clear. The purpose of this study was to determine whether interleukin (IL)-1 mediates burn-induced inducible nitric oxide synthase (iNOS) expression, peroxynitrite production, and lung damage through c-Jun NH2-terminal kinase (JNK) signaling. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Thermal injury models in the mice. INTERVENTIONS: IL-1 receptor type 1 (IL-1R1) mice, Tnfrsf1a mice, and wild-type (WT) mice were subjected to 30% total body surface area third-degree burn. The JNK inhibitor, SP600125, was given to mice to study the involvement of the JNK pathway in thermal injury-induced lung damage. WT --> WT, WT --> IL-1R1, and IL 1R1 --> WT chimeric mice were generated to determine the role of hematopoietic cells in IL-1-mediated lung damage. Neutrophils were harvested and treated in vitro with N-formyl-methionyl-leucyl-phenylalanine (fMLP). MEASUREMENTS AND MAIN RESULTS: IL-1R1 mice rather than Tnfrsf1a mice showed less thermal injury-induced lung damage. IL-1R1 mice displayed less lung JNK activity; intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), chemokine receptor 2 (CXCR2), and macrophage inflammatory protein-2 (MIP2), messenger RNA expression; myeloperoxidase activity; and neutrophil p38 mitogen-activated protein kinase (MAPK) phosphorylation after thermal injury. SP600125 significantly reduced thermal injury-induced blood dihydrorhodamine (DHR) 123 oxidation, iNOS expression, and lung permeability in WT mice but not in IL-1R1 mice. IL-1R1 --> WT chimeric mice rather than WT --> IL-1R1 chimeric mice showed less thermal injury-induced lung damage. fMLP increased reactive oxygen species (ROS) production of neutrophils in WT mice but not in IL-1R1 mice. SP600125 decreased ROS production of neutrophils in WT mice but not in IL-1R1 mice. CONCLUSIONS: Thermal injury-induced lung JNK activation; lung ICAM, VCAM, CXCR2, and MIP2 expression; and DHR 123 oxidation are IL-1 dependent. JNK inhibition decreases IL 1-mediated thermal injury-induced lung damage. Given that the IL-1 receptor is critical in thermal injury-induced p38 MAPK phosphorylation and ROS production of neutrophils, we conclude that IL-1 mediates thermal injury-induced iNOS expression and lung damage through the JNK signaling pathway. PMID- 17334238 TI - Relationship between sublingual and intestinal microcirculatory perfusion in patients with abdominal sepsis. AB - OBJECTIVE: To evaluate the relation between sublingual and intestinal microcirculatory alterations in patients with abdominal sepsis. DESIGN: Prospective observational study. SETTING: A 23-bed mixed intensive care unit of a tertiary teaching hospital. PATIENTS: Twenty-three patients with abdominal sepsis and a newly constructed intestinal stoma were included in the study group. Nineteen outpatient healthy individuals with an intestinal stoma and ten nonsepsis patients with a <24-hr-old intestinal stoma were included as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Orthogonal polarization spectral imaging of the sublingual and intestinal microcirculation was performed on days 1 and 3. In addition, variables of systemic hemodynamics, such as cardiac index, heart rate, blood pressure, central venous pressure, and dosages of vasopressor and inotropic agents, were obtained. On day 1 there was no correlation of the microvascular flow index between the sublingual and intestinal microcirculatory beds (Spearman's rho [rs] = .12; 95% confidence interval, -.51 to .31; p = .59). Furthermore, there was no significant correlation between microcirculatory alterations and variables of systemic circulation (rs 2 mg/dL within 48 hrs of admission). DESIGN: Prospective, multicenter cohort study. SETTING: Thirty-two medical, surgical, and mixed intensive care units. PATIENTS: A total of 38,036 adult patients admitted consecutively over a period of 4 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Excluding patients with preexisting cirrhosis (n = 691; 1.8%) and acute or acute-on-chronic hepatic failure (n = 108, 0.3%), we identified 4,146 patients (10.9%) with early hepatic dysfunction. These patients had different baseline characteristics, longer median intensive care unit stays (5 vs. 3 days; p < .001) and increased hospital mortality (30.4% vs. 16.4%; p < .001). Hepatic dysfunction was also associated with higher observed-to-expected mortality ratios (1.02 vs. 0.91; p < .001). Multiple logistic regression analysis showed an independent mortality risk of hepatic dysfunction (odds ratio, 1.86; 95% confidence interval, 1.71-2.03; p < .001), which exceeded the impact of all other organ dysfunctions. A case-control study further confirmed these results: Patients with early hepatic dysfunction exhibited significantly increased raw and risk-adjusted mortality compared with control subjects. CONCLUSIONS: Our results provide strong evidence that early hepatic dysfunction, occurring in 11% of critically ill patients, presents a specific and independent risk factor for poor prognosis. PMID- 17334251 TI - Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. AB - OBJECTIVE: The purpose of this study was to examine the outcome implications of implementing a severe sepsis bundle in an emergency department as a quality indicator set with feedback to modify physician behavior related to the early management of severe sepsis and septic shock. DESIGN: Two-year prospective observational cohort. SETTING: Academic tertiary care facility. PATIENTS: Patients were 330 patients presenting to the emergency department who met criteria for severe sepsis or septic shock. INTERVENTIONS: Five quality indicators comprised the bundle for severe sepsis management in the emergency department: a) initiate central venous pressure (CVP)/central venous oxygen saturation (Scvo2) monitoring within 2 hrs; b) give broad-spectrum antibiotics within 4 hrs; c) complete early goal-directed therapy at 6 hrs; d) give corticosteroid if the patient is on vasopressor or if adrenal insufficiency is suspected; and e) monitor for lactate clearance. MEASUREMENTS AND MAIN RESULTS: Patients had a mean age of 63.8 +/- 18.5 yrs, Acute Physiology and Chronic Health Evaluation II score 29.6 +/- 10.6, emergency department length of stay 8.5 +/- 4.4 hrs, hospital length of stay 11.3 +/- 12.9 days, and in-hospital mortality 35.2%. Bundle compliance increased from zero to 51.2% at the end of the study period. During the emergency department stay, patients with the bundle completed received more CVP/Scvo2 monitoring (100.0 vs. 64.8%, p < .01), more antibiotics (100.0 vs. 89.7%, p = .04), and more corticosteroid (29.9 vs. 16.2%, p = .01) compared with patients with the bundle not completed. In a multivariate regression analysis including the five quality indicators, completion of early goal-directed therapy was significantly associated with decreased mortality (odds ratio, 0.36; 95% confidence interval, 0.17-0.79; p = .01). In-hospital mortality was less in patients with the bundle completed compared with patients with the bundle not completed (20.8 vs. 39.5%, p < .01). CONCLUSIONS: Implementation of a severe sepsis bundle using a quality improvement feedback to modify physician behavior in the emergency department setting was feasible and was associated with decreased in-hospital mortality. PMID- 17334252 TI - Comparison of three different methods of evaluation of metabolic acid-base disorders. AB - OBJECTIVES: The Stewart approach states that pH is primarily determined by Pco2, strong ion difference (SID), and nonvolatile weak acids. This method might identify severe metabolic disturbances that go undetected by traditional analysis. Our goal was to compare diagnostic and prognostic performances of the Stewart approach with a) the traditional analysis based on bicarbonate (HCO3) and base excess (BE); and b) an approach relying on HCO3, BE, and albumin-corrected anion gap (AGcorrected). DESIGN: Prospective observational study. SETTING: A university-affiliated hospital intensive care unit (ICU). PATIENTS: Nine hundred thirty-five patients admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Stewart approach detected an arterial metabolic alteration in 131 (14%) of patients with normal HCO3- and BE, including 120 (92%) patients with metabolic acidosis. However, 108 (90%) of these patients had an increased AGcorrected. The Stewart approach permitted the additional diagnosis of metabolic acidosis in only 12 (1%) patients with normal HCO3, BE, and AGcorrected. On the other hand, the Stewart approach failed to identify 27 (3%) patients with alterations otherwise observed with the use of HCO3-, BE, and AGcorrected (16 cases of acidosis and 11 of alkalosis). SID and BE, and strong ion gap (SIG) and AGcorrected, were tightly correlated (R2 = .86 and .97, p < .0001 for both) with narrow 95% limits of agreement (8 and 3 mmol/L, respectively). Areas under receiver operating characteristic curves to predict 30-day mortality were 0.83, 0.62, 0.61, 0.60, 0.57, 0.56, and 0.67 for Sepsis-related Organ Failure Assessment (SOFA) score, SIG, AGcorrected, SID, BE, HCO3-, and lactates, respectively (SOFA vs. the rest, p < .0001). CONCLUSIONS: In this large group of critically ill patients, diagnostic performance of the Stewart approach exceeded that of HCO3- and BE. However, when AGcorrected was included in the analysis, the Stewart approach did not offer any diagnostic or prognostic advantages. PMID- 17334253 TI - Heparin-induced thrombocytopenia in intensive care patients. AB - OBJECTIVE: To summarize new information on frequency of heparin-induced thrombocytopenia (HIT) in patients treated in intensive care units (ICU), developments in the interpretation of assays for detecting anti-PF4/heparin antibodies, and treatment of HIT patients. STUDY SELECTION: All data on the frequency of laboratory-confirmed HIT in ICU patients were included; for laboratory testing of HIT and treatment of patients, this review focuses on recent data that became available in 2005 and 2006. DATA EXTRACTION AND SYNTHESIS: HIT is a potentially life-threatening adverse effect of heparin treatment caused by platelet-activating antibodies of immunoglobulin G class usually recognizing complexes of platelet factor 4 and heparin. HIT is more often caused by unfractionated heparin than low-molecular-weight heparin and is more common in postsurgical than in medical patients. In the ICU setting, HIT is uncommon (0.3-0.5%), whereas thrombocytopenia from other causes is very common (30-50%). For laboratory diagnosis of HIT antibodies, both antigen assays and functional (platelet activation) assays are available. Both tests are very sensitive (high negative predictive value) but specificity is problematic, especially for the antigen assays, which also detect nonpathogenic immunoglobulin M and immunoglobulin A class antibodies. Detection of immunoglobulin M or immunoglobulin A antibodies could potentially lead to adverse events such as bleeding if a false diagnosis of HIT prompts replacement of heparin by an alternative anticoagulant. For treatment of HIT, three alternative anticoagulants are approved: the direct thrombin inhibitors, lepirudin and argatroban, and the heparinoid, danaparoid (not approved in the United States). Recent data indicate that the approved dosing regimens of the direct thrombin inhibitors are too high, especially in ICU patients. CONCLUSIONS: HIT affects <1% of ICU patients even though 30-50% develop thrombocytopenia. The choice of the optimal alternative anticoagulant depends on patient characteristics. Many ICU patients require lower doses of alternative anticoagulant than those recommended by the manufacturer. PMID- 17334254 TI - Pericontusional brain tissue exhibits persistent elevation of lactate/pyruvate ratio independent of cerebral perfusion pressure. AB - OBJECTIVE: To determine whether pericontusional tissue exhibits neurochemical responsiveness to changes in cerebral perfusion pressure as measured by microdialysis lactate/pyruvate ratio. DESIGN: Prospective monitoring with retrospective data analysis. SETTING: Single-center academic neurologic intensive care unit. PATIENTS: Twenty-one patients with severe traumatic brain injury (Glasgow Coma Scale score 3-8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebral microdialysis was performed for the initial 7 days after traumatic brain injury. Thirteen patients had microdialysis probes in normal tissue and eight had two probes, one of which was located in pericontusional tissue. Retrospective analysis was performed to determine if microdialysis levels in pericontusional tissue demonstrates higher levels of lactate/pyruvate ratio than normal tissue and if lactate/pyruvate ratio increased with reductions in cerebral perfusion pressure. Univariate analysis revealed higher values for glutamate and lactate/pyruvate ratio in pericontusional tissue compared with normal tissue. However, based on the mixed-effects model analysis, the percent time of elevated lactate/pyruvate ratio was significantly higher in pericontusional tissue (40 +/- 59% vs. 17 +/- 37%, p < .05), and the mean lactate/pyruvate ratio values showed only a trend relationship (62 +/- 134 vs. 34 +/- 78, p < .06). When examined by cerebral perfusion pressure threshold, cerebral perfusion pressure <60 mm Hg was not associated with higher lactate/pyruvate ratio values in normal or pericontusional tissue. In addition, no single cerebral perfusion pressure threshold was associated with a significant reduction in lactate/pyruvate ratio in either pericontusional or normal tissue (p < .08). CONCLUSIONS: Sustained increases in lactate/pyruvate ratio occurred more frequently in pericontusional tissue compared with normal brain tissue. The lactate/pyruvate ratio was not related to cerebral perfusion pressure, nor was the percent time-burden of elevated lactate/pyruvate ratio related to any particular sustained cerebral perfusion pressure threshold. Lactate/pyruvate ratio values appear to be elevated despite cerebral perfusion pressure values customarily considered to be adequate. PMID- 17334255 TI - Early modifiable factors associated with fatal outcome in patients with severe traumatic brain injury: a case control study. AB - OBJECTIVE: Survival of patients with severe traumatic brain injury may be improved by minimizing secondary brain injury. We aimed to identify potentially modifiable contributors to secondary brain injury that may persist and adversely affect patient outcome. DESIGN: Retrospective case control study. Nonsurviving patients with traumatic brain injury were selected and matched 1:1 for age, Glasgow Coma Scale score, Abbreviated Injury Scale: Head (AISHEAD), Revised Trauma Score, and Injury Severity Score with survivors. Potentially modifiable contributors to secondary brain injury were examined and compared in both groups. SETTING: A level I trauma center in Melbourne, Australia. PATIENTS: Patients with traumatic brain injury caused by blunt trauma with an AISHEAD >or=4 were identified from a prospective intensive care database. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between January 1, 1999, and July 30, 2000, 74 patients, including 37 nonsurvivors, were identified. By design, the groups were well matched for injury severity and baseline conditions. In nonsurvivors, mean arterial pressure was similar to that of survivors at hospital arrival but was lower at 4 hrs after arrival (71 +/- 16 vs. 80 +/- 15 mm Hg, p = .016). A mean arterial pressure or=3 days were randomly assigned to undergo insertion of silver impregnated catheters (silver group) or standard catheters (standard group). Catheter colonization was defined as the growth of >or=1,000 colony-forming units in culture of the intravascular tip of the catheter by the vortexing method. Diagnosis of catheter-related infection was performed by an independent and blinded expert committee. RESULTS: A total of 320 catheters were studied in the silver group and 297 in the standard group. Characteristics of the patients, insertion site, duration of catheterization (median, 11 vs. 10 days), and other risk factors for infection were similar in the two groups. Colonization of the catheter occurred in 47 (14.7%) vs. 36 (12.1%) catheters in the silver and the standard groups (p = .35), for an incidence of 11.2 and 9.4 per 1,000 catheter days, respectively. Catheter-related bloodstream infection was recorded in eight (2.5%) vs. eight (2.7%) catheters in the silver and the standard groups (p = .88), for an incidence of 1.9 and 2.1 per 1,000 catheter days, respectively. CONCLUSION: The use of silver-impregnated multi-lumen catheters in adult intensive care patients is not associated with a lower rate of colonization than the use of standard multi-lumen catheters. PMID- 17334257 TI - Clinical application of mild therapeutic hypothermia after cardiac arrest. AB - OBJECTIVE: Postresuscitative mild hypothermia lowers mortality, reduces neurologic impairment after cardiac arrest, and is recommended by the International Liaison Committee on Resuscitation. The European Resuscitation Council Hypothermia After Cardiac Arrest Registry was founded to monitor implementation of therapeutic hypothermia, to observe feasibility of adherence to the guidelines, and to document the effects of hypothermic treatment in terms of complications and outcome. DESIGN: Cardiac arrest protocols, according to Utstein style, with additional protocols on cooling and rewarming procedures and possible adverse events are documented. SETTING: Between March 2003 and June 2005, data on 650 patients from 19 sites within Europe were entered. PATIENTS: Patients who had cardiac arrest with successful restoration of spontaneous circulation were studied. MEASUREMENTS AND MAIN RESULTS: Of all patients, 462 (79%) received therapeutic hypothermia, 347 (59%) were cooled with an endovascular device, and 114 (19%) received other cooling methods such as ice packs, cooling blankets, and cold fluids. The median cooling rate was 1.1 degrees C per hour. Of all hypothermia patients, 15 (3%) had an episode of hemorrhage and 28 patients (6%) had at least one episode of arrhythmia within 7 days after cooling. There were no fatalities as a result of cooling. CONCLUSIONS: Therapeutic hypothermia is feasible and can be used safely and effectively outside a randomized clinical trial. The rate of adverse events was lower and the cooling rate was faster than in clinical trials published. PMID- 17334258 TI - Patient safety event reporting in critical care: a study of three intensive care units. AB - OBJECTIVE: To increase patient safety event reporting in three intensive care units (ICUs) using a new voluntary card-based event reporting system and to compare and evaluate observed differences in reporting among healthcare workers across ICUs. DESIGN: Prospective, single-center, interventional study. SETTING: A medical ICU (19 beds), surgical ICU (24 beds), and cardiothoracic ICU (17 beds) at a 1,371-bed urban teaching hospital. PATIENTS: Adult patients admitted to these three study ICUs. INTERVENTIONS: Use of a new, internally designed, card based reporting program to solicit voluntary anonymous reporting of medical errors and patient safety concerns. MEASUREMENTS AND MAIN RESULTS: During a 14 month period, 714 patient safety events were reported using a new card-based reporting system, reflecting a significant increase in reporting compared with pre-intervention Web-based reporting (20.4 reported events/1,000 patient days pre intervention to 41.7 reported events/1,000 patient days postintervention; rate ratio, 2.05; 95% confidence interval, 1.79-2.34). Nurses submitted the majority of reports (nurses, 67.1%; physicians, 23.1%; other reporters, 9.5%); however, physicians experienced the greatest increase in reporting among their group (physicians, 43-fold; nurses, 1.7-fold; other reporters, 4.3-fold) relative to pre-intervention rates. There were significant differences in the reporting of harm by job description: 31.1% of reports from nurses, 36.2% from other staff, and 17.0% from physicians described events that did not reach/affect the patient (p = .001); and 33.9% of reports from physicians, 27.2% from nurses, and 13.0% from other staff described events that caused harm (p = .005). Overall reported patient safety events per 1,000 patient days differed by ICU (medical ICU = 55.5, cardiothoracic ICU = 25.3, surgical ICU = 40.2; p < .001). CONCLUSIONS: This card based reporting system increased reporting significantly compared with pre intervention Web-based reporting and revealed significant differences in reporting by healthcare worker and ICU. These differences may reveal important preferences and priorities for reporting medical errors and patient safety events. PMID- 17334259 TI - Patient-ventilator interaction and sleep in mechanically ventilated patients: pressure support versus proportional assist ventilation. AB - OBJECTIVES: To understand the role of patient-ventilator asynchrony in the etiology of sleep disruption and determine whether optimizing patient-ventilator interactions by using proportional assist ventilation improves sleep. DESIGN: Randomized crossover clinical trial. SETTING: A tertiary university medical surgical intensive care unit. PATIENTS: Thirteen patients during weaning from mechanical ventilation. INTERVENTIONS: Patients were randomized to receive pressure support ventilation or proportional assist ventilation on the first night and then crossed over to the alternative mode for the second night. Polysomnography and measurement of light, noise, esophageal pressure, airway pressure, and flow were performed from 10 pm to 8 am. Ventilator settings (pressure level during pressure support ventilation and resistive and elastic proportionality factors during proportional assist ventilation) were set to obtain a 50% reduction of the inspiratory work (pressure time product per minute) performed during a spontaneous breathing trial. MEASUREMENTS AND MAIN RESULTS: Arousals per hour of sleep time during pressure support ventilation were 16 (range 2-74) and 9 (range 1-41) during proportional assist ventilation (p = .02). Overall sleep quality was significantly improved on proportional assist ventilation (p < .05) due to the combined effect of fewer arousals per hour, fewer awakenings per hour (3.5 [0-24] vs. 5.5 [1-24]), and greater rapid eye movement (9% [0-31] vs. 4% [0-23]), and slow wave (3% [0-16] vs. 1% [0-10]) sleep. Tidal volume and minute ventilation were lower on proportional assist ventilation, allowing for a greater increase in Paco2 during the night. Patient ventilator asynchronies per hour were lower with proportional assist ventilation than with pressure support ventilation (24 +/- 15 vs. 53 +/- 59; p = .02) and correlated with the number of arousals per hour (R = .65, p = .0001). CONCLUSIONS: Patient ventilator discordance causes sleep disruption. Proportional assist ventilation seems more efficacious than pressure support ventilation in matching ventilatory requirements with ventilator assistance, therefore resulting in fewer patient-ventilator asynchronies and better quality of sleep. PMID- 17334261 TI - Postirradiation sinus mucosa disease in nasopharyngeal carcinoma patients. AB - OBJECTIVES/HYPOTHESIS: We sought to determine the incidence, progression, and risk factors for postirradiation sinus mucosa diseases (SMD) incidentally found on follow-up magnetic resonance images MRIs) in nasopharyngeal carcinoma (NPC) patients. STUDY DESIGN: RETROSPECTIVE. METHODS: The medical records, pre- and postradiotherapy (RT) MRIs were reviewed in NPC patients. Lund-Mackay system for staging of rhinosinusitis (Lund score) was used as a tool for investigation. RESULTS: One hundred twelve NPC patients (77 males and 35 females) were recruited in this study. The distribution of tumor staging in these patients were 39 (34.8%) patients in T1,23(20.5%) in T2, 31(27.7%) in T3, and 19 (17.0%) in T4 by MRI staging before RT. In these 62 patients with normal sinus ventilation before RT, 42 (67.7%) patients returned to having SMDs 3 months after RT. The maxillary,anterior ethmoid, and posterior ethmoid sinuses were most readily affected. In patients with SMDs at 3 months postRT, advanced tumor stage (P = .013) and smoking habit (P =.047) were the two factors that significantly influence Lund score. When comparing Lund score with different times after radiation therapy, a trend of decrease in Lund score could be noted from 3 months to 3 years after irradiation. CONCLUSIONS: The incidence and severity of SMD was found to be highest at 3 months postRT and decreased gradually with time. Conservative management with clinical symptom correlation should be attempted first in these patients. In these NPC patients,advanced tumor stage and smoking habit would predispose them to SMD development. PMID- 17334263 TI - Acquisition of surgical skills for endonasal skull base surgery: a training program. AB - INTRODUCTION: Endonasal surgery represents a radical change in the practice of cranial base surgery and requires the acquisition of new knowledge and surgical skills. The optimal training program for surgeons has not been established. METHODS: We reviewed our experience with endonasal cranial base surgery from 1998 to 2006 to develop a training plan for the acquisition of surgical skills. It consists of a modular and incremental approach to endonasal skull base surgery that is designed to train surgeons to function as a team, learn endoscopic skull base anatomy, and develop fundamental endoscopic skills. RESULTS: Stages of training are established for the otolaryngologist-head and neck surgeon and the neurosurgeon that are based on level of technical difficulty, potential risk of vascular and neural injury, and unfamiliar endoscopic anatomy. Mastery of each level is recommended before attempting procedures at a higher level. CONCLUSIONS: Standardization of training and the adoption of a modular, incremental training program are expected to facilitate the training of endonasal surgeons in both surgical specialties. Adherence to such a program during the growth phase of endoscopic skull base surgery may decrease the risk of complications as the surgeon's knowledge and surgical expertise develop. PMID- 17334264 TI - Viagra, methamphetamine, and HIV risk: results from a probability sample of MSM, San Francisco. AB - OBJECTIVES: To determine the prevalence and factors of Viagra use in combination with crystal methamphetamine and its association with HIV risk behavior in a probability sample of men who have sex with men (MSM). STUDY DESIGN: A cross sectional, random-digit dial telephone survey of MSM in San Francisco conducted between June 2002 and January 2003. RESULTS: Of the 1976 MSM, 13.5% used Viagra alone, 7.1% used methamphetamine without Viagra, 9.6% used Viagra with a mood altering substance (excluding methamphetamine), and 5.1% used Viagra with methamphetamine. Of the MSM using Viagra with methamphetamine, 57% were HIV infected and 24% of these men reported serodiscordant unprotected insertive intercourse. Viagra used with methamphetamine was independently associated with a higher risk of serodiscordant unprotected insertive intercourse, serodiscordant unprotected receptive intercourse, and a recent diagnosis of a sexually transmitted disease. CONCLUSION: MSM who use Viagra with crystal methamphetamine have high prevalence rates of HIV and engage in HIV risk behaviors. PMID- 17334265 TI - Detection and quantification of Y-chromosomal sequences by real-time PCR using the LightCycler system. PMID- 17334267 TI - Profiles of decline in activities of daily living in non-Alzheimer dementia. AB - Assessment of functional ability is an essential component in the clinical diagnosis of dementia. Most studies have primarily focused on disability due to Alzheimer disease (AD), and less is known about profiles of functional impairment in other dementia syndromes. Functional ability was assessed in individuals in the early stages of AD (N=100), the behavioral variant of frontotemporal dementia (FTD) (N=57), and primary progressive aphasia (PPA) (N=61), using the activities of daily living questionnaire (Johnson et al, 2004). The average duration of illness for the 3 groups ranged from 3.4 to 3.9 years. Overall level of functional impairment and the profile of abilities across subscales of Self-Care, Household Care, Employment and Recreation, Shopping and Money, Travel, and Communication were examined. Results showed that overall functional ability was moderately impaired in AD and FTD, and mildly impaired in PPA. For all groups, more complex ADLs were impaired early on, with relative preservation of self-care activities. The Communication score was the least impaired next to Self-Care for FTD and AD, and the most impaired for PPA patients. The activities of daily living questionnaire may capture aspects of preserved functioning that are not apparent from patients' scores on cognitive tests, especially for those with aphasia. PMID- 17334266 TI - Neuropathologic heterogeneity in HDDD1: a familial frontotemporal lobar degeneration with ubiquitin-positive inclusions and progranulin mutation. AB - Hereditary dysphasic disinhibition dementia (HDDD) describes a familial disorder characterized by personality changes, and language and memory deficits. The neuropathology includes frontotemporal lobar atrophy, neuronal loss and gliosis and, in most cases, abundant Abeta plaques and neurofibrillary tangles (NFTs). A Pick/Alzheimer's spectrum was proposed for the original family (HDDD1). Here we report the clinicopathologic case of an HDDD1 individual using modern immunohistochemical methods, contemporary neuropathologic diagnostic criteria to distinguish different frontotemporal lobar degenerations (FTLDs), and progranulin (PRGN) mutation analysis. Clinical onset was at age 62 years with personality changes and disinhibition, followed by nonfluent dysphasia, and memory loss that progressed to muteness and total dependence with death at age 84 years. There was severe generalized brain atrophy (weight=570 g). Histopathology showed superficial microvacuolation, marked neuronal loss, gliosis, and ubiquitin positive, tau-negative cytoplasmic and intranuclear neuronal inclusions in frontal, temporal, and parietal cortices. There were also frequent neuritic plaques and NFTs in parietal and occipital cortices. The case met neuropathologic criteria for both FTLD with ubiquitin-positive, tau-negative inclusions (FTLD-U), and Alzheimer disease (Braak NFT stage V). We discovered a novel pathogenic PGRN mutation c.5913 A>G (IVS6-2 A>G) segregating with FTLD-U in this kindred. In conclusion, HDDD1 is an FTLD-U caused by a PGRN mutation and is neuropathologically heterogeneous with Alzheimer disease as a common comorbidity. PMID- 17334269 TI - Social cognition: an early impairment in dementia of the Alzheimer type. AB - OBJECTIVE: A core component of social functioning is the capacity to attribute mental states to others and to understand intention as psychologic cause. The hypothesis of this study was that dementia of the Alzheimer type (DAT) patients show an impaired understanding of psychologic cause although they remain able to understand physical causality. METHODS: To test this hypothesis, 20 elderly adults with DAT, 20 healthy age-matched controls, and 20 healthy young adults were presented a cartoon task requiring them to process physical or psychologic cause of events. RESULTS: Patients with DAT at onset scored significantly lower than controls when they had to reason about psychologic causation, while they did not differ for reasoning about physical causation. Consistent with these results, patients with DAT showed significantly lower scores in psychologic reasoning as compared with their scores for physical causality. Instead young and elderly healthy adults scored similarly for the 2 types of causality and the 2 groups did not differ in their scores. These results suggest that impaired understanding of intention in others may be considered as an early socio-cognitive index of onset of DAT. A post hoc division of the group of patients with DAT into 2 subgroups according to Mini Mental State (MMS) scores showed that the group with the more severe MMS scores not only had lower scores for psychologic causality but also showed impairment in reasoning about physical causality involving persons. Physical causality involving objects remained relatively preserved. CONCLUSIONS: The remarkable deficit in attribution of intention in our patients with DAT at onset and the following deterioration of their performance in reasoning about physical causality with persons may reflect progressive dysfunction of the superior temporal sulcus in Alzheimer disease. PMID- 17334268 TI - Cerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia. AB - Expansion of the cerebral ventricles may occur at an accelerated rate in subjects with dementia, but the time course of expansion during transitions between normal cognitive function, mild cognitive impairment (MCI), and dementia is not well understood. Furthermore, the effects of cardiovascular risk factors on rate of ventricular expansion are unclear. We used a fully automated segmentation technique to measure change rate in lateral ventricle-to-brain ratio (VBR) on 145 longitudinal pairs of magnetic resonance images of subjects in the Cardiovascular Health Study Cognition Study from the Pittsburgh Center. A multivariate model analyzed VBR change rate, accounting for dementia statuses at both imaging times (normal, MCI, or dementia), age, sex, education, race, magnetic resonance-defined infarcts, Center for Epidemiology Studies Depression Scale, baseline ventricular volume, and cardiovascular risk factors. VBR change was faster in subjects who were demented or transitioned from MCI to dementia, compared with subjects normal at both images and subjects who transitioned from normal to MCI or dementia. Patients with diabetes had faster VBR change. Ventricular expansion may accelerate late in the progression from normal cognitive function to dementia, and may be modulated by diabetes. PMID- 17334270 TI - Wandering behavior and Alzheimer disease. The REAL.FR prospective study. AB - We evaluated the predictive value of wandering behavior at baseline for nutritional status, disability, institutionalization, and mortality in 686 Alzheimer disease community-dwelling subjects enrolled in the prospective REAL.FR study, France. Wandering behavior was defined using the Neuro-Psychiatric Inventory. The Mini-Nutritional Assessment and Katz Activity of Daily Living (ADL) scale were administered every 6 months during the 2 years of the study. Dementia severity was assessed using the Mini-Mental State Examination. Behavioral disturbances, comorbidities, medication, health care support, and burden status of the caregiver were assessed at the baseline visit. Outcomes of the 83 (12.2%) wanderers were compared with those of the nonwanderers. In the whole sample 30.1%/year subjects lost weight, 27.8%/year worsened their nutritional status, 55.1%/year decreased their ADL score, 11%/year reduced their ability to walk, 13.5%/year were institutionalized, and 6.2%/year died. Wanderers differed from nonwanderers by a higher frequency of decline of the ADL score (P<0.001), and institutionalization (P<0.001). Adjusted for baseline characteristics, risk of worsening the nutritional status, weight loss, decreased ADL score, and death were not statistically different between wanderers and nonwanderers. Risk for undernutrition and death are not increased in wanderers. Their higher risk of ADL disabilities and institutionalization are partly explained by their baseline characteristics. PMID- 17334271 TI - Evaluated need, costs of care, and payer perspective in degenerative dementia patients cared for in the United States. AB - The purpose of this study was to examine the strength of the associations between 5 measures of need that are potentially modifiable in degenerative dementia patients and direct costs of care from 5 payer perspectives in the US healthcare system. Data were derived from a cohort study of 150 patients with a degenerative dementia. We measured need variables at baseline and utilization of healthcare in the year before and after baseline. Utilization data were converted into estimated direct costs and totaled based on the costs paid for by 5 payers in the US healthcare system. Path models were used to quantify and compare the relationships between need variables and direct costs. From Medicare's perspective, comorbid medical conditions were the most important predictor of Medicare costs. From Medicaid's perspective, neuropsychiatric symptoms and signs of parkinsonism were additional significant predictors. From the perspective of patients, their families and society, all 5 need variables were significant predictors of direct costs (ie, those above, plus cognitive impairment, and dependency). The relationship between evaluated need variables and direct costs depends on the perspective of the payer and provide insights into which need variables could be targeted with interventions to control costs and improve patient outcomes. PMID- 17334272 TI - Decision making on behalf of elders with advanced cognitive impairment: family transitions. AB - Changes in family decision making responsibilities occur with progression of cognitive impairment. Focus groups with family members of nursing home residents with advanced cognitive impairment investigated values and beliefs used in making decisions for the elder. Family members described difficult decisions they had made to date, noting a significant transition in their decision making role when the elders' decisions needed to be superseded (especially with changes in living arrangements). In most families, one person or couple assumed the principal decision making responsibility. When decisions were made in the context of family conflict, managing the conflict became the focus, rather than the elder's care. In such cases, the elder's previously stated wishes regarding end of life care were not as likely to be honored. PMID- 17334273 TI - Degenerative dementias and their medical care in the movies. AB - Compared with other neurologic problems, few films have been dedicated to degenerative dementia. To our knowledge, this is the first systematic review about the way in which dementia patients and their medical care are described in films. Twenty-four of the 53 relevant films that were found in online movie databases could be viewed. The author describes the demographics of the characters suffering from dementia, the clinical picture including neuropsychiatric manifestations, diagnostic procedures, medical follow-up, pharmacologic and nonpharmacologic treatment and the attitude of the caregivers. Most characters are played by actors in their seventh or eighth decade. There is an overrepresentation of highly educated people. Although the clinical picture is often accurate, some films suggest that even in the late stages of the disease patients have sudden moments of full insight in their disease. Among the neuropsychiatric signs, activity disturbances and aggressiveness are most often described. Few patients seek medical help, only 2 patients take acetylcholinesterase inhibitors and follow-up is absent for 5 of the 11 relevant patients. Only in 10 of 23 films, the term "Alzheimer" is used. Although there is a growing cinematographic interest in Alzheimer patients, even recent films tend to reinforce therapeutic and even diagnostic nihilism. PMID- 17334274 TI - Memantine treatment of cognitive symptoms in mild to moderate Alzheimer disease: secondary analyses from a placebo-controlled randomized trial. AB - Memantine, an N-methyl-D-aspartate receptor antagonist, is approved in the United States and Europe for the treatment of moderate to severe Alzheimer disease (AD) and has also been investigated in patients with mild to moderate AD. To characterize the specific cognitive benefits of memantine in patients with mild to moderate AD, a post hoc analysis was conducted of a 24-week randomized, double blind, placebo-controlled, clinical trial comparing memantine (10 mg twice daily) to placebo. Cognition was assessed using the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) total score, individual items, and aggregated subscales, using a mixed model repeated measures analysis. As assessed by the ADAS-cog total score, participants in the placebo group demonstrated significantly more cognitive decline from baseline than participants treated with memantine at all visits beginning at week 8. Subjects treated with placebo also declined significantly more than individuals in the memantine group on 5 of 11 ADAS-cog individual items: orientation, language, comprehension, word finding, and recall of test instructions. Out of 3 ADAS-cog aggregated item subscales (language, memory, and praxis), outcomes in 2 (language and memory) favored memantine. Consistent with findings from trials conducted in moderate to severe AD patients, this post hoc analysis of a randomized clinical trial suggests that memantine benefits core aspects of language and some aspects of memory in patients with mild to moderate AD. PMID- 17334275 TI - Category fluency as a screening test for Alzheimer disease in illiterate and literate patients. AB - Brief cognitive tests are widely used for dementia screening, but are usually influenced by education. The present work aimed to determine education-adjusted cut-off scores and correspondent sensitivity (S) and specificity (Sp) values of the category fluency (CF) test (animals/min) as a screening tool for Alzheimer disease (AD). Eighty-eight patients with mild AD and 117 normal matched controls were evaluated. Patients and controls were divided into 4 groups according to educational level (illiterates, 1 to 3, 4 to 7, and > or =8 y) and were administered the CF test. In each group, cut-off values were determined using Receiver Operator Characteristic analysis. The areas under Receiver Operator Characteristic curves were 0.922/0.914/0.963/0.954, for the identification of AD among the groups of illiterates, 1 to 3, 4 to 7, and > or =8 years of education, respectively. The cut-off points for each group were 9 (S=90.5% and Sp=80.6%) for illiterates; 12 (S=95.2%% and Sp=80.0%) for 1 to 3 years; 12 (S=91.3% and Sp=91.9%) for 4 to 7 years, and 13 for those with > or =8 years (S=82.6% and Sp=100.0%). These results suggest that the CF may be a useful screening test for mild AD in different educational levels, with the need of using specific cut-off scores adjusted for each range of schooling. PMID- 17334276 TI - Low back pain suppresses preparatory and triggered upper-limb activation after sudden upper-limb loading. AB - STUDY DESIGN: A cross-sectional comparative study between healthy controls and patients with chronic low back pain (LBP). OBJECTIVE: To assess the effect of chronic LBP on biceps brachii muscle activation during sudden upper-limb loading. SUMMARY OF BACKGROUND DATA: Chronic LBP is related to altered trunk muscle function. However, it is not known if these changes are also found in upper-limb function, indicating a general effect. METHODS: Surface electromyographic recordings were made from the biceps brachii bilaterally from 22 control subjects without chronic LBP and 29 patients with chronic LBP. Electromyography was recorded during expected and unexpected limb loading, with the activation pattern recorded for analysis at 150 milliseconds before loading, and 3 consecutive 50 milliseconds periods following loading. RESULTS.: Chronic LBP patients had decreased biceps brachii activation before expected perturbation (P = 0.035) and during the third 50-millisecond period (from 100 to 150 milliseconds) after unexpected perturbation (P = 0.010). During the first 2, 50-millisecond periods (from 0 to 100 milliseconds) after the perturbation, the activation was similar. CONCLUSIONS: Chronic LBP did not affect reflex activation of biceps brachii muscles but decreased preparatory and triggered reactions. The finding indicates that back pain may disturb higher level information processing in motor control. PMID- 17334277 TI - Improvements in general practitioner beliefs and stated management of back pain persist 4.5 years after the cessation of a public health media campaign. AB - STUDY DESIGN: Quasi-experimental, nonrandomized, nonequivalent, parallel group controlled study involving before-after mailed surveys of general practitioners. OBJECTIVES: To measure the magnitude of any sustained change in general practitioner beliefs and stated behavior about back pain 4.5 years after cessation of a media campaign designed to alter population back pain beliefs. SUMMARY OF BACKGROUND DATA: A media campaign providing simple advice about back pain carried out in Victoria, Australia between September 1997 and December 1999 resulted in significant improvements in physicians' beliefs and stated management. METHODS: Mailed surveys of general practitioners in Victoria and the adjacent control state, New South Wales, were performed before, immediately after, and 4.5 years after the Victorian campaign. We elicited knowledge and attitudes about back pain by asking respondents to indicate their level of agreement with a set of statements. We also elicited their likely management by presenting 2 hypothetical scenarios. RESULTS: A total of 635 Victorian and 511 NSW GPs completed the latest survey. There were sustained improvements over time in Victorian physicians' beliefs about back pain and their stated behavior: e.g., at Survey 3, compared with baseline, Victorian physicians were 2.0 (95% confidence interval [CI], 1.3-3.0) times as likely as their NSW counterparts to know that patients with low back pain need not wait to be almost pain free to return to work; 1.78 (95% CI, 1.27-2.49) times as likely not to order tests for acute low back pain and 0.47 (95% CI, 0.33-0.69) times as likely to order lumbosacral radiographs. They were also 0.49 (95% CI, 0.34-0.73) times as likely to prescribe bed rest and 1.62 (95% CI, 1.19-2.22) times as likely to advise work modification. CONCLUSIONS: A population-based strategy to shift societal views about back pain has had a sustained effect on GP beliefs and stated behavior 4.5 years after its cessation. PMID- 17334278 TI - Suspected atlantoaxial rotatory fixation-subluxation: the value of multidetector computed tomography scanning under general anesthesia. AB - STUDY DESIGN: Clinical case reports and radiologic study. OBJECTIVES: To emphasize the value of computed tomography (CT) scan under general anesthesia in order to prevent misdiagnosing atlantoaxial rotatory fixation-subluxation in children with acute torticollis. SUMMARY OF BACKGROUND DATA: A "cock-robin" posture clinically characterizes painful rotatory fixation of the atlantoaxial joint in children. Classically, the observation of persistent displacement of the dens between the lateral mass of the atlas and asymmetry of the atlantoaxial joint on radiography confirmed the diagnosis. More recently, (dynamic) CT scanning or magnetic resonance imaging is used to confirm the diagnosis. However, when a CT scan is performed with the head of the patient in the "cock-robin" position, there is a serious chance of misinterpretation due to the abnormal anatomic position of the atlantoaxial joint. METHODS: Four consecutive cases of children presenting with an acute torticollis were analyzed. All were neurologically intact. A conventional single-slice CT scan made with the head rotated in the "cock-robin" position confined rotatory dislocation of the atlantoaxial joint. Subsequently, the patients were referred to our hospital for further treatment. To confirm the diagnosis before potential treatment, a multidetector CT scan under general anesthesia was performed in all 4. RESULTS: The multidetector CT scans under general anesthesia did not show any abnormalities. All patients were treated conservatively and recovered completely within 4 weeks of being referred to our hospital. CONCLUSIONS: Multidetector CT scanning under general anesthesia is recommended in children when there is suspicion for a spontaneously developed atlantoaxial rotatory fixation subluxation. PMID- 17334279 TI - Delayed presentation of cervical ligamentous instability without radiologic evidence. AB - STUDY DESIGN: A case of delayed presentation of unstable cervical ligamentous injury without radiologic evidence is presented. OBJECTIVES: To report a rare case of delayed presentation of cervical ligamentous injury without radiologic evidence, and to discuss diagnosis, initial management, and techniques of operative stabilization. SUMMARY OF BACKGROUND DATA: The literature is reviewed. METHODS: A 48-year-old man who sustained a nondisplaced unilateral C6 pillar fracture with no radiologic evidence of ligamentous injury returned for follow-up with radicular pain and bilateral perched facets at C5-C6. RESULTS: Closed reduction of the cervical subluxation was performed via cervical traction, and subsequent surgical stabilization was undertaken with anterior cervical discectomy and instrumented arthrodesis of C5-C6 with structural interbody autograft. The patient wore a cervical brace for 6 weeks after surgery, and progressed to a stable fusion with pain resolution and no neurologic sequelae. CONCLUSIONS: This is a rare reported case of delayed presentation of an unstable ligamentous injury in a nondisplaced cervical pillar fracture without initial radiologic evidence of instability. If any reason to suspect ligamentous injury exists, workup with upright cervical lateral radiographs, flexion/extension radiographs, or magnetic resonance imaging should be obtained. Awake, closed reduction with cervical traction followed by surgical stabilization with an anterior discectomy and instrumented arthrodesis with structural autograft achieved stable fixation. PMID- 17334282 TI - Fibroblast growth factor-2 maintains the differentiation potential of nucleus pulposus cells in vitro: implications for cell-based transplantation therapy. AB - STUDY DESIGN: To investigate effects of FGF-2 on nucleus pulposus cell growth and differentiation. OBJECTIVES: To elucidate the phenotypic changes that occur during expansion of nucleus pulposus cells in monolayer culture, and to investigate the effects of fibroblast growth factor (FGF)-2 on cell growth and differentiation. SUMMARY OF BACKGROUND DATA: Nucleus pulposus cells would have a limited application for autologous cell transplantation if phenotypic dedifferentiation takes place during culture expansion. FGF-2 has been shown to retain the differentiation potential of monolayer expanded chondrocytic cells. However, its effect on nucleus pulposus cells is not known. METHODS: Bovine nucleus pulposus cells were serially passaged in the presence or absence of FGF-2 (1 and 10 ng/mL). After passage numbers 1 and 7, cells were immobilized in alginate beads and treated with transforming growth factor (TGF)-beta1 for 1 week to assess their differentiation. RESULTS: During culture expansion in monolayer, nucleus pulposus cells maintained the expression of aggrecan messenger ribonucleic acid (mRNA). However, mRNA levels of collagen type I, collagen type II, Sox-9, and versican decreased with increasing passage number for both control (untreated) cells and FGF-2 treated cells. When grown in alginate with TFG-beta1, passage 7 cells that received FGF-2 during culture expansion restored the mRNA expression of type II collagen, Sox-9, COMP, chondroadherin, and fibromodulin. Moreover, FGF-2 treatment resulted in increased sulfated proteoglycan synthesis and lower aggrecan turnover compared to untreated controls under identical culture conditions. FGF-2 treated cells continued to express HIF-1alpha protein till passage 7, while MMP-2 expression was evident in cells treated with TGF beta1. In addition, cells pretreated with FGF-2 showed higher induction of phospho ERK1/2 after treatment with TGF-beta1. Also, FGF-2 maintained smad 2/smad 3 mediated signaling in cells after TGF-beta treatment. FGF-2 action resulted in reduced actin stress fiber formation and migratory cell morphology, with no effect on cell proliferation. CONCLUSIONS: The presence of FGF-2 during culture expansion of nucleus pulposus cells in monolayer can sustain a differentiated cell phenotype by maintaining responsiveness to TGF-beta1. Our results suggest that FGF-2 should be tested for its ability to maintain the reactivity of the nucleus pulposus cells to other morphogenic factors that may be used for cell based transplantation therapy. PMID- 17334283 TI - Intradiscal thermal therapy using interstitial ultrasound: an in vivo investigation in ovine cervical spine. AB - STUDY DESIGN: In vivo investigation of intradiscal ultrasound thermal therapy in ovine cervical spine model. OBJECTIVE: To evaluate the potential of interstitial ultrasound for selective heating of intradiscal tissue in vivo. SUMMARY OF BACKGROUND DATA: Application of heat in the spine using resistive wire and radiofrequency current heating devices is currently being used clinically for minimally invasive treatment of discogenic low back pain. Treatment temperatures are representative of those required for thermal necrosis of ingrowing nociceptor nerve fibers and disc cellularity alone, or with coagulation and restructuring of anular collagen in the high temperature case. METHODS: Two interstitial ultrasound applicator design configurations with directional heating patterns were evaluated in vivo in ovine cervical intervertebral discs (n = 62), with up to 45-day survival periods. Two heating protocols were employed in which the temperature measured 5 mm away from the applicator was controlled to either <54 C (capable of nerve and cellular necrosis) or >70 C (for coagulation of collagen) for a 10-minute treatment period. Transient and steady state temperature maps, calculated thermal doses (t43), and histology were used to assess the thermal treatments. RESULTS: These studies demonstrated the capability to control spatial temperature distributions within selected regions of the in vivo intervertebral disc and anular wall using interstitial ultrasound. CONCLUSIONS: Ultrasound energy is capable of penetrating within the highly attenuating disc tissue to produce more extensive radial thermal penetration, lower maximum intradiscal temperature, and shorter treatment times than can be achieved with current clinical intradiscal heating technology. Thus, interstitial ultrasound offers potential as a more precise and faster heating modality for the clinical management of low back pain and studies of thermal effects on disc tissue in animal models. PMID- 17334284 TI - Segmental motion adjacent to anterior cervical arthrodesis: a prospective study. AB - STUDY DESIGN: Prospective, observational study. OBJECTIVE: The present study describes in a prospective setting the kinematics changes occurring at segments adjacent to a one-level cervical arthrodesis. SUMMARY OF BACKGROUND DATA: The development of adjacent segment disease has been noticed by many clinicians. Whether symptoms develop due to fusion induced accelerated spondylosis or due to a natural development in a predisposed person is currently under debate. The motivation for introducing motion preservation procedures in the neck is primarily to protect the patients from developing symptomatic adjacent disc disease. To accept this rationale, it has to be demonstrated that a fusion creates an unfavorable biomechanical situation at adjacent levels. METHODS: Forty six patients underwent standard anterior cervical decompression and fusion using a cylindrical cage implant. Lateral radiographic views of the cervical spine in flexion and extension were obtained before surgery, and at 12 months of follow up. Employing Distortion Compensated Roentgen Analysis, rotational and translational motion at adjacent levels was quantified prospectively. RESULTS: Rotational and translational motion at adjacent cranial and caudal levels did not exhibit a significant change between the preoperative state and the state 12 months after the operation. CONCLUSION: The assumption of an iatrogenically caused increased mobility by a one-level cervical fusion could not be confirmed 12 months after surgery. PMID- 17334285 TI - Radiographic assessment and quantitative motion analysis of the cervical spine after serial sectioning of the anterior ligamentous structures. AB - STUDY DESIGN: Cadaveric study of a diagnostic test for cervical spine instability. OBJECTIVE: Determine if flexion-extension (FE) radiographs can be used to detect incremental damage to anterior cervical structures. SUMMARY OF BACKGROUND DATA: Prior studies have shown that damage to cervical structures can alter motion between vertebrae, and FE radiographs are sometimes used to detect this damage. However, no study has determined if FE radiographs are sensitive and specific for acute injury. METHODS: FE radiographs were taken of the intact neck and after each incremental increase in damage to the anterior structures. Intervertebral motion was quantified using previously validated methods. The sensitivity and specificity of intervertebral motion measurements were assessed. RESULTS: Motion within the intact spines was within normal ranges. Although intervertebral rotation changed significantly after certain anterior structures were damaged, rotation frequently remained within normal ranges, even after extensive damage. A center of rotation that was posterior to the 95% confidence interval for normal motion was 100% sensitive and specific for damage to the anterior structures of the spine. CONCLUSIONS: The results suggest that extensive damage to the anterior cervical spine could be missed if instability assessment was based on intervertebral rotation or displacements measured from FE radiographs. In contrast, a center of rotation that was located posterior to normal was both sensitive and specific for damage to anterior structures. PMID- 17334286 TI - Evaluation of spinal kinematics following lumbar total disc replacement and circumferential fusion using in vivo fluoroscopy. AB - STUDY DESIGN: In vivo fluoroscopic analysis of lumbar spinal motion with total disc replacement (TDR), fusions, and controls. OBJECTIVES: Compare and contrast lumbar spinal motion profiles in TDR, circumferential fusion, and controls. SUMMARY OF BACKGROUND DATA: TDR has been shown to preserve motion and possibly prevent abnormal loading at the adjacent level. Although in vitro cadaveric studies have provided invaluable information, they are not capable of assessing the physiologic motion profile of the lumbar spine that is initiated and stabilized by in vivo trunk muscular contractions. METHODS: Cross-sectional evaluation using high-frequency low-dose pulsated video fluoroscopy to evaluate lumbar spinal motion in subjects who underwent TDR (n = 8), circumferential fusion (n = 5), and controls (n = 4). Angulation and translation were recorded at 20 time points during the extension-flexion arc. Motion gradients, or slopes of the motion curves, were generated to allow for comparison of lumbar spinal motion profiles. RESULTS: Circumferential fusions exhibited significantly steeper motion gradients at the proximal adjacent level compared with TDR during flexion. TDR had more physiologic motion profiles at the proximal adjacent level than fusions during flexion and extension. At operative levels L4/5 and L5/S1, TDR and controls exhibited similar motion profiles in flexion, while fusions exhibited significantly less motion. In extension, however, TDR had a steeper slope than controls at the L4/5 operative level. Between L3 and S1, the total range of motion accounted for by the L4/5 proximal adjacent level was 59% in 1-level fusions, 38% in 1-level TDR, and 29% in controls. While no control or TDR subjects underwent sagittal plane translation >3 mm during flexion-extension, 80% of fusions did (average 3.7 mm), most notably during the latter phase of extension. CONCLUSIONS: TDR produces physiologic lumbar spinal motion profiles in flexion and extension at the operative and proximal adjacent levels. Fusions, however, produced steeper motion gradients at the proximal adjacent level, while undergoing significantly greater sagittal plane translation during flexion extension. PMID- 17334287 TI - Comparison of one-level posterior lumbar interbody fusion performed with a minimally invasive approach or a traditional open approach. AB - STUDY DESIGN: Prospective cohort study. OBJECTIVES: To determine the statistical difference between the minimally invasive and traditional open approach for one level instrumented posterior lumbar interbody fusion by comparing the perioperative data, clinical outcome, and radiographic result. SUMMARY OF BACKGROUND DATA: Posterior lumbar fusion performed with mini-incision using tubular retractor has been advocated as a minimally invasive technique. Proponents have claimed that minimally invasive techniques reduce postoperative pain, blood loss, transfusion needs, and the length of hospital stay compared with the traditional open techniques. But there was no well-designed comparison study that supports these claims. METHODS: We studied a consecutive series of 61 patients who underwent one-level PLIF procedure (32 cases performed with minimally invasive approach and 29 cases with traditional open approach) by one surgeon at one hospital, from October 2003 until October 2004. The following data were compared between the 2 groups with 1-year minimum follow-up: the clinical and radiographic results, surgical time, estimated blood loss, transfusion needs, postoperative back pain by visual analogue scale, time needed before ambulation, length of hospital stay, and complications. RESULTS: There was no significant difference between the 2 groups in the aspects of the clinical and radiographic results with 1-year minimum follow-up. The minimally invasive group was found to have a significantly less blood loss, less needs of transfusion, less postoperative back pain, shorter recovery time before ambulation, and shorter length of hospital stay. However, the minimally invasive group needed significantly longer surgical time and showed 2 cases of technical complications. CONCLUSIONS: The present study, which was based on the authors' initial experience with the minimally invasive approach, could confirm favorable results reported by previous uncontrolled cohort studies in the aspects of less blood loss, less transfusion need, less postoperative back pain, quicker recovery, and shorter hospital stay. It also showed the similar surgical efficacy of the minimally invasive approach with that of the traditional open technique. However, the minimally invasive technique needs longer surgical time and a prudent attention to lower the risk of technical complications. Further long-term, prospective studies involving a larger study group are needed to determine the benefits of this minimally invasive percutaneous procedure. PMID- 17334288 TI - Outcomes of surgical treatment in male versus female adolescent idiopathic scoliosis patients. AB - STUDY DESIGN: This research was part of a multicenter study of the surgical treatment of adolescent idiopathic scoliosis (AIS). OBJECTIVE: To compare the radiographic and perioperative surgical treatment outcomes of male AIS patients with female AIS patients. SUMMARY OF BACKGROUND DATA: The results of treatment in male patients with idiopathic scoliosis have not been widely reported. Only 1 study has evaluated the differences in operative treatment outcomes between male and female patients with AIS. METHODS: Data were collected for patients who met the indications for surgical intervention at 8 separate institutions. Radiographic, perioperative, and pulmonary function variables for male and female AIS patients treated surgically were analyzed. A univariate analysis of variance with the alpha level adjusted to P < or = 0.01 was used. RESULTS: The data for 547 (449 females and 98 males) patients were included in this analysis. Posterior instrumentation (vs. anterior instrumentation) was performed slightly more often in males than females (51% vs. 44%, respectively). The preoperative primary curve magnitude was similar for both genders, but flexibility was less in males (44% vs. 49%; P = 0.01). Postoperative percent correction and the ratio of percent correction to preoperative flexibility were both similar in males versus females. Analysis of the perioperative variables yielded that estimated blood loss was higher in males than females (1342 vs. 898 cc, respectively; P = 0.001). Males reported greater pain on postoperative day 1 (6.1 vs. 5.4; P = 0.01), however, conversion to oral pain medication was similar for both. Preoperative and postoperative pulmonary function was similar for both genders. CONCLUSION: Male AIS patients had slightly more rigid primary curves compared to females but a similar degree of postoperative scoliosis correction. Differences in the preoperative status and perioperative course did not compromise the outcomes of surgical treatment as in all other measures; the results were comparable between the genders. PMID- 17334289 TI - Evaluation of postoperative residual spinal deformity and patient outcome in idiopathic scoliosis patients in Japan using the scoliosis research society outcomes instrument. AB - STUDY DESIGN: This study clarifies the correlation between the components of the Scoliosis Research Society Outcomes Instrument (SRS-24) and the radiographic parameters after surgery in Japanese idiopathic scoliosis patients. OBJECTIVES: To investigate the correlation between the magnitude of back deformity after scoliosis surgery and the components of the SRS-24. SUMMARY OF BACKGROUND DATA: Patient outcomes for Japanese scoliosis patients using the SRS-24 have not been fully investigated. METHODS: Idiopathic scoliosis patients (n = 81) who were treated with surgery and followed up for more than 2 years were evaluated. Radiographic examination included Cobb angle, rotation angle of apical vertebrae, and translation of the C7 vertebra from the center sacral line on the coronal plane. In addition, the score of one new question regarding postoperative scar was investigated and compared with that of the individual SRS-24 domains. RESULTS: A comparison of the SRS-24 and radiographic results revealed a significant inverse correlation between total pain and the postoperative correction of the rotation angle in the thoracic curve (rs = 0.27; P < 0.05). General self-image was inversely correlated with the Cobb angle (rs = -0.23; P < 0.05) and the rotation angle (rs = -0.30; P < 0.01) in the thoracic curve. Self image after surgery was positively correlated with the correction degree of the thoracic Cobb angle (rs = 0.27; P < 0.05); 60% of patients had some concerns regarding postoperative scar, and the concerned patients demonstrated significantly lower scores in the pain and general self-image domains (P < 0.05) than the unconcerned patients did. CONCLUSION: Patients with a greater Cobb angle or rotation angle in the thoracic curve had a negative self-image. Self-image improved after surgery by greater correction of the thoracic Cobb angle. Thoracic scoliotic deformity with prominence should be substantially reduced by the surgical treatment to improve satisfaction rates and self-image regarding back appearance. Additionally, physicians should pay more attention to patients' concern regarding their postoperative scars to obtain better outcomes. PMID- 17334290 TI - Comparison of thoracic pedicle screw to hook instrumentation for the treatment of adult spinal deformity. AB - STUDY DESIGN: Retrospective, case-control, matched cohort. OBJECTIVE: Compare the radiographic and clinical outcomes of adult spinal deformity patients treated with thoracic pedicle screw (TPS) or thoracic hook constructs. SUMMARY OF BACKGROUND DATA: The efficacy of TPS instrumentation for pediatric spinal deformity correction has been established. Little is known about TPS use in adult spinal deformity. METHODS: Fifty-six patients (average age, 49 years; average follow-up, 3.58 years) were treated with TPS or thoracic hook constructs for coronal (n = 20) or sagittal (n = 36) plane deformities. Patients were evaluated radiographically and with SRS scores. RESULTS: Coronal deformities treated with TPS demonstrated improved main thoracic curve correction compared with hook constructs at last follow-up (24.8 degrees vs. 13.8 degrees; P < 0.05), despite having larger (59.8 degrees vs. 44.9 degrees; P < 0.05) and more rigid preoperative curves (29.3% vs. 44.9% correction on side-bending radiographs; P < 0.001). Sagittal deformities treated with TPS constructs demonstrated greater thoracolumbar kyphosis correction than hook constructs at last follow-up (12.1 degrees vs. 2.5 degrees; P < 0.05). No TPS patient had a thoracic pseudarthrosis. Four hook patients (14%) had thoracic pseudarthroses. CONCLUSIONS: TPS instrumentation allows greater coronal and sagittal plane correction and may reduce the risk of thoracic pseudarthrosis compared with hook constructs when treating adult spinal deformities. PMID- 17334291 TI - Three-dimensional analysis of formation failure in congenital scoliosis. AB - STUDY DESIGN: Morphologic analysis was performed by 3-dimensional (3D) CT in 75 patients with congenital scoliosis exhibiting formation failure. OBJECTIVES: The objectives of this study were to conduct 3D analysis of the morphology of spinal malformation and to elucidate the association between malformed vertebrae and adjacent vertebrae. SUMMARY OF BACKGROUND DATA: The morphology of spinal malformation has conventionally been evaluated by plain radiograph radiography. Although the usefulness of 3D CT has recently been reported, these reports have only demonstrated that this technique allows more detailed evaluation than plain radiography. METHODS: We examined the morphology of the posterior components in spinal malformation of formation failure and evaluated the association between the anterior and posterior components by 3D CT. We clarified the morphologic variations of the posterior components in spinal malformation by dividing 75 cases of formation failure into solitary and multiple numbers of malformed vertebrae and into simple and complex modes of malformation between anterior and posterior components. RESULTS: Thirty-three patients exhibited a single malformed vertebra in the entire spine (solitary malformation group), while the other 42 had multiple malformed vertebrae (total, 102 malformed vertebrae: multiple malformation group). The multiple malformation group consisted of 26 patients (57 malformed vertebrae) in whom the cause of scoliosis could be explained separately for each of the malformed vertebrae and 16 patients (45 malformed vertebrae) in whom the structure was complicated and the cause of scoliosis could not be explained for each of the malformed vertebra. CONCLUSION: There were morphologic variations of the posterior components of malformed vertebrae. A completely new complex malformation in which the mechanism of formation failure may differ from the conventionally proposed mechanisms was also found. PMID- 17334292 TI - Reliability of 3D reconstruction of the spine of mild scoliotic patients. AB - STUDY DESIGN: A reliability study was conducted in quantitative 3-dimensional (3D) measurements for mild scoliosis. OBJECTIVE: To evaluate the intrarater and interrater reliability of a computer tool used for 3D reconstruction of the spine. SUMMARY OF BACKGROUND DATA: No reliability study of spinal in vivo 3D medical imaging measurements has been performed in the literature. METHODS: This study included 30 patients (mean age 13 years) with mild idiopathic scoliosis. Spinal 3D reconstruction was performed using a new technique called semiautomatic 3D reconstruction, which requires only the location of the corners of each vertebral body on 2 orthogonal views. Three raters performed the 3D reconstruction procedure on the 30 pairs of radiographs in random order. One of the raters repeated the procedure for the 30 patients 15 days later. Inter reliability and intra-reliability were estimated for different parameters: thoracic kyphosis, lumbar lordosis, Cobb's angle, pelvic morphologic and positional parameters, and axial rotation. RESULTS: Intraclass correlation coefficient showed good or very good agreement for most of the measurements. The 95% prediction limits are approximately 4 degrees for the measurements of spinal curves, 2 degrees for pelvic parameters, and axial vertebral rotation. CONCLUSIONS: The reliability of 3D reconstruction of the spine is acceptable, and this technique can be used for clinical studies. PMID- 17334293 TI - Radiologic assessment of all unfused lumbar segments 7.5 years after instrumented posterior spinal fusion. AB - STUDY DESIGN: Prospective observational single-cohort study. OBJECTIVE: To analyze long-term radiographic changes in all unfused lumbar segments after instrumented posterolateral lumbar fusion. SUMMARY OF BACKGROUND DATA: Adjacent segment degeneration (ASD) after lumbar fusion may be a consequence of biomechanical stress or result from constitutional factors. Most studies analyzing ASD only investigate the motion segments immediately above and below the fusion. None compares adjacent segments to all the other unfused segments after instrumented posterior fusion. METHODS: Using the distortion-compensated roentgen analysis method, disc height, dorsoventral displacement, and lordosis were measured in 212 unfused segments from 62 patients, on digitized standing radiographs taken before fusion surgery and after a mean follow-up of 7.5 years (range, 4-11 years). The effect of covariables, such as age, length of follow-up, fusion level, number of fused segments, and sagittal and spinopelvic parameters on the preoperative to follow-up changes, were analyzed using a repeated measurement model. RESULTS: No changes were observed at the segments located below the fusion. All the unfused segments above the fusion showed the same significant loss of disc height. Loss of disc height did not depend on fusion parameters, correlated weakly with age and length of follow-up, and correlated highly across adjacent unfused segments. CONCLUSIONS: After posterior lumbar instrumented fusion, radiographic changes suggesting disc degeneration appear homogeneously at several levels cephalad to fusion and seem to be determined by individual characteristics. PMID- 17334294 TI - Responsiveness of pain and disability measures for chronic whiplash. AB - STUDY DESIGN: Cohort study. OBJECTIVE: To evaluate the responsiveness of common pain and disability measures in a cohort of patients with chronic whiplash. SUMMARY OF BACKGROUND DATA: Pain and disability are routinely measured in clinical practice and clinical research. However, to date, a head-to-head comparison of competing measures for whiplash patients has not been performed. METHODS: Pain (pain intensity, bothersomeness, and SF-36 bodily pain score) and disability (Patient Specific Functional Scale, Neck Disability Index, Functional Rating Index, Copenhagen Scale, and SF-36 physical summary) measures were completed by 132 patients with chronic whiplash at baseline and then again after 6 weeks together with an 11-point global perceived effect scale. Internal responsiveness was evaluated by calculating effect sizes and standardized response means, and external responsiveness by correlating change scores with global perceived effect scores and by ROC curves. RESULTS: The ranking of responsiveness was consistent across the different analyses. Pain bothersomeness was more responsive than pain intensity, which was more responsive than the SF-36 pain measure. The Patient Specific Functional Scale was the most responsive disability measure, followed by the spine-specific measures, with the SF-36 physical summary measure the least responsive. CONCLUSION: Pain bothersomeness and the Patient Specific Functional Scale provide the most responsive measures of pain and disability, respectively, in patients with chronic whiplash. PMID- 17334295 TI - Psychosocial variables in patients with (sub)acute low back pain: an inception cohort in primary care physical therapy in The Netherlands. AB - STUDY DESIGN: A prospective cohort study of patients with episodes of acute or subacute low back pain, seeking physical therapy in primary care, with follow-up at weeks 2, 4, 8, and 12. OBJECTIVES: To evaluate the association between psychosocial factors and the transition from acute or subacute low back pain to chronicity. SUMMARY OF BACKGROUND DATA: Psychosocial factors have long been thought to be associated with chronic pain only. Recent prospective studies, however, suggest that these factors may also be important in acute or subacute low back pain. METHODS: Demographic, psychosocial, and psychological baseline data were collected and analyzed from a sample of 66 acute or subacute patients with low back pain in order to predict the 3-month outcome. RESULTS: After 3 months, response rate was 85% (56 patients). Forty-five percent rated their current status as "not recovered." Twelve percent reported work absenteeism. Using multiple regression analyses, baseline scores on the Acute Low Back Pain Screening Questionnaire, Pain Coping Inventory, Fear-Avoidance Beliefs Questionnaire, and Tampa Scale for Kinesiophobia were not significantly associated with non-recovery at 3 months. The only significant predictor at baseline was the subscale pain of the ALBPSQ, correctly classifying 80% of the patients. The relative risk for not being recovered was 3.72 (95% confidence interval, 1.63-8.52) for the subjects with high scores on the subscale for pain. Pain scores and scores on psychosocial variables at 12 weeks were not associated. CONCLUSIONS: The study strongly revealed pain-related items to be essential factors in the development of chronicity and long-term disability in primary care physical therapy. Health status at 8 weeks seems crucial in developing chronicity. PMID- 17334296 TI - Measurement techniques for upper cervical spine injuries: consensus statement of the Spine Trauma Study Group. AB - STUDY DESIGN: Literature review. OBJECTIVES: The Spine Trauma Study Group compiled a collection of clinically useful imaging methods used in upper cervical spine trauma and standardized how these measurements are documented. SUMMARY OF BACKGROUND DATA: Imaging of the upper cervical spine is crucial for injury detection, description, and treatment decision making. However, a standard set of imaging measurement techniques for this region does not exist. While most clinicians have developed their own methods of describing radiographic pathology, this variability often leads to confusion in developing an agreed on classification system and in proposing universal treatment recommendations. METHODS: The available literature concerning measurement of injury characteristics after upper cervical trauma was reviewed. Consensus of the most clinically applicable measurement methods among the surgeon members of the Spine Trauma Study Group was achieved. RESULTS: The techniques include: the basion-dens and basion-posterior axial line intervals (C0-C2); fracture gap and fracture length apposition (a reflection of fragment size) for occipital condyle injuries; lateral articular overhang for C1 ring fractures; the atlanto-dens and posterior atlanto-dens intervals for sagittal C1-C2 instability; odontoid fracture angulation and displacement; and C2-C3 angulation and translation for traumatic spondylolisthesis of the axis. CONCLUSIONS: Only through prospective study using a standardized and uniform set of measurement techniques can the clinical significance of these imaging characteristics be fully appreciated. PMID- 17334297 TI - Internal thoracic vessels used as pedicle graft for anastomosis with vascularized bone graft to reconstruct C7-T3 spinal defects: a new technique. AB - STUDY DESIGN: A report of 4 cases of primary bone tumors (3 cases) or infection (1 case) at the cervicothoracic junction treated with resection-reconstruction. OBJECTIVES: To document a new technique using the internal thoracic vessels as recipient vessels for reconstruction of the cervicothoracic spine with free vascularized fibula grafts. SUMMARY OF BACKGROUND DATA: The cervicothoracic junction is a difficult region in reconstructive spinal surgery. Although nonvascularized fibula grafts can be used to reconstruct the osseous defect, compared with free vascularized fibula grafts they are biomechanical weaker, incorporate less well, are less resistant to infection, and remodel incomplete in time. However, when using free vascularized bone grafts, the selection of suitable recipient vessels remains one of the most critical decisions. MATERIALS AND METHODS: Four patients who had a primary tumor (3 cases) or a severe progressive kyphotic deformity and progressive neurologic symptoms due to tuberculosis (1 case) were treated by resection and vascularized reconstruction. In 3 patients, a staged anteroposterior en bloc resection of T1-T3 (2 cases) or T1-T2 (1 case) was performed; the ventral reconstruction of the osseous defect consisted of a vascularized fibula graft interposition between C7-T4 (2 cases) or C7-T3 (1 case). In another case, an axial slot was milled through the T1-T2 vertebral bodies to accept an osteotomized vascularized fibular graft. In all cases, a free vascularized fibula graft was used: the vascular anastomosis was performed between the peroneal and the dissected and rerouted internal thoracic vessels. The anterior construction was strengthened by a ventral plate-screw system. RESULTS: The resection-reconstruction procedures, including the dissection, rerouting, and anastomosis between the internal thoracic vessels and the peroneal vessels, were successfully performed. At present, all patients are alive, and there is no evidence of recurrent disease, unchanged, or improved neurologic with a mean follow-up of 28 months. All grafts are well incorporated. CONCLUSIONS.: A combined low anterolateral cervical and midsternal approach or a midline sternotomy allows not only a safe and excellent exposure to the cervicothoracic junction but also to the internal thoracic vessels. The internal thoracic vessels are appropriate donor vessels: its longevity, diameter, length, and rerouting capacity allow vascularized graft reconstruction of vertebral column defects of the low cervical (C6-C7) and/or upper thoracic (T1-T3) region. PMID- 17334298 TI - Dr. Ahmet Munir Sarpyener: pioneer in definition of congenital spinal stenosis. AB - Although there are many reports regarding the spinal surgical applications before the 19th century, the definition of spinal disorders and application of the most novel surgical techniques have been performed in last 2 centuries. Lumbar spinal stenosis was reported in the first half of the 20th century. The definition of the lumbar spinal stenosis was commonly attributed to Dr. Verbiest. However, there were some reports regarding the symptoms attributable to lumbar spinal stenosis before him. On the other hand, Dr. Sarpyener, a Turkish surgeon, reported for the first time congenital spinal stenosis, a special variety of spinal stenosis. The aim of this study is to review the biography, scientific studies, and spine applications of Dr. Sarpyener, a pioneer in the field of spina bifida and congenital spinal stenosis. PMID- 17334299 TI - Prevalence and etiology of hearing loss in rural Nicaraguan children. AB - OBJECTIVE/HYPOTHESIS: The prevalence and causes of pediatric hearing loss (HL) in the developing world are largely unknown. Infectious sequelae, ototoxic medications, and genetic causes may play a larger role in developing countries. In addition, the significance of GJB2 mutation gene in poorly developed areas remains unclear. The intent of this study is to investigate the prevalence and etiology of HL in children living in a remote, impoverished region of northern Nicaragua. STUDY DESIGN: Cross-sectional study. METHODS: Clinical data from two sources were analyzed: data from screening examinations performed in rural schools in the Department of Jinotega, Nicaragua (group A) and pediatric HL patients seen at the Otolaryngology and Audiology Clinic in Jinotega, Nicaragua (group B). Patients with congenital HL were offered a genetic test for GJB2 mutations. Comparisons were made using parametric (analysis of variance) and nonparametric (Kruskal-Wallis) tests. RESULTS: School-based screening examinations (group A) revealed a high prevalence of significant HL (>30 dB) of 18%. The majority of these children had normal otoscopic examinations (58%). A family history of HL was seen in 24% of children who failed screening exams. Positive family history was more common in patients with HL (P < .01) and in specific schools (P < .05). Clinic-based evaluations (group B) reveal a population with predominantly severe-profound HL. Physical dysmorphism was common, yet identifiable syndromic HL was rare. Although familial HL was common (33%), there were no pathologic GJB2 mutations. Other common risk factors in this population were maternal infection during pregnancy, neonatal distress, low birth weight or prematurity, and gentamicin exposure. CONCLUSIONS: HL in this rural, third world environment is more prevalent, and the etiologies responsible in this study group are different from those encountered in industrialized nations. Poor perinatal health care, infectious causes, gentamicin exposure, and hereditary HL are potentially preventable causes that play a major role in this population. PMID- 17334300 TI - The skin cancer index: clinical responsiveness and predictors of quality of life. AB - OBJECTIVE: To establish the clinical responsiveness of the Skin Cancer Index (SCI), a new disease-specific quality of life (QOL) instrument, and to assess demographic and clinical factors which impact QOL in patients with nonmelanoma skin cancer (NMSC). STUDY DESIGN: Prospective study of 183 patients with NMSC of the face and neck referred to a tertiary care Mohs surgery clinic. METHODS: The SCI is a 15 item, validated, disease-specific QOL instrument with 3 distinct subscales, Emotion, Social, and Appearance. Higher scores reflect better QOL. The SCI and the Dermatology Life Quality Index (DLQI), a general dermatology instrument, was administered at initial consultation and 4 months after surgical treatment. Multivariate analysis was conducted to assess demographic and clinical factors predictive of QOL for both instruments. RESULTS: The SCI total score and all three subscale scores increased with treatment, demonstrating strong evidence of responsiveness over time (P < .001) in contrast with the DLQI (P = .46). Predictors of poorer QOL for the SCI included female sex and cancers located on the lip. Patients who demonstrated greatest improvement in QOL with treatment included those who were younger (<50 yr) and had lower reported household income. Also, first time NMSC patients and those patients who underwent less extensive reconstructions demonstrated greater improvements in QOL. CONCLUSION: The SCI is a sensitive and responsive QOL instrument for patients with NMSC. Distinct demographic and clinical variables that impact QOL have been demonstrated using this multidimensional, disease-specific instrument. PMID- 17334301 TI - Cold dissection versus coblation-assisted adenotonsillectomy in children. AB - OBJECTIVE: To compare intraoperative efficiency and postoperative recovery between cold dissection adenotonsillectomy (CDA) and coblation-assisted adenotonsillectomy (CAA). METHODS: A prospective, randomized, single-blind trial of pediatric patients aged 2 to 16 years undergoing adenotonsillectomy was conducted. Patients were randomized to undergo either CDA or CAA. Measured intraoperative parameters included surgical duration and intraoperative blood loss. Measured postoperative parameters included a 14 day caregiver questionnaire that recorded a daily pain rating using the Wong-Baker FACES pain scale, pain medication use, days to return to a normal diet, and days to return to a normal caregiver routine. Postoperative complications were also recorded. Intraoperative and postoperative measures were statistically compared between groups. RESULTS: Forty-six children with a mean age of 6.7 years (23 CDA and 23 CAA) were randomized and completed the study. Mean age and sex distributions were similar between groups (P > .05). Surgical times were significantly shorter for the CAA group versus the CDA group (11.2 min vs. 17.0 min, P < .001). Intraoperative blood loss was statistically lower for both the adenoidectomy and tonsillectomy portions of the procedure for the CAA group versus the CDA group (P < .001 and P < .001, respectively). There was no statistically significant difference in reported daily pain scores between groups (P = .296, analysis of variance). Both groups returned to normal diet (P = .982), and caregivers returned to their normal routine on similar postoperative days (P = .631). CONCLUSIONS: CAA offers better operative speed and intraoperative hemostasis as compared with CDA. However, CAA does not result in poorer postoperative pain scores or recoveries despite these intraoperative advantages. PMID- 17334302 TI - Quality of life after facial nerve repair. AB - OBJECTIVES: Analyze the postoperative quality of life (QoL) in patients after surgical nerve repair for facial nerve lesion. STUDY DESIGN: Descriptive study using questionnaire data and medical chart review. METHODS: Forty-nine patients answered the Short Form-36 (SF-36), the European Organization for Research and Treatment (EORTC) questionnaires QLQ-C30 and QLQ-HN35, and a modification of the Acoustic Neuroma Hospital of Norway Survey. Facial function was self-evaluated by the patients using the House-Brackmann (HB) scale and the Stennert index (SI). The questionnaire data were analyzed in relation to the medical chart data. RESULTS: The follow-up time ranged from 12 to 202 months. The underlying disease was benign in 34 (61%) patients and malignant in 15 (39%) patients. Facial nerve repair was successful in all patients, with a mean HB scale of 3.1, a mean SI of 4.9, and a mean May grading of 2.7. The facial function self-evaluation was not significantly different. Seventy-five percent of the patients were satisfied with the operation. The SF-36 demonstrated a significantly lower social functioning, emotional role, general mental health, and vitality lower than in the normal German population. In the EORTC QLQ C30, emotional function was low and the insomnia rate high. EORTC QLQ HN35 showed a high rate of trouble with social eating, less sexuality, problems opening mouth, and weight gain problems. Age 45 years or older, female sex, May grading 3 or greater, SI self-assessment 5 or greater, HB self-assessment greater than 2 had a significant negative effect on some QoL items, but not factors such as type or histology of the disease or delayed reconstruction. CONCLUSIONS: Although grading of facial function after nerve repair revealed satisfying results, the patients experience a reduced QoL. PMID- 17334303 TI - The navigation-controlled drill in temporal bone surgery: a feasibility study. AB - BACKGROUND: This study examines the feasibility of a navigation-controlled (NC) drill for surgery on the petrosal bone in an experimental environment. According to the principle of NC, the drill is to be switched off automatically once the borders of the workspace are exceeded during a mastoidectomy. MATERIALS AND METHODS: The registration is based on an optical navigation system with navigation software (MiMed). As surgery engine, the Unidrive-system (Karl Storz GmbH & CO. Kg, Tuttlingen, Germany) was integrated. The definition of the workspace was performed manually in axial computed tomography (CT) slices of the petrosal bone phantom. The mastoidectomy on the model was accomplished in three runs with 10 trial surgeons altogether (5 experienced [exp.] in otologic (ear) surgery, 5 inexperienced [nonexp.]). During each run, the following were logged: the total length of time for the procedure as well as the number and extent of injuries to the risk structures (facial nerve, horizontal semicircular canal, sigmoid sinus). The resultant petrosal bone cavities were measured on the CT. RESULTS: The time for the segmentation of the workspace for the mastoidectomy amounted to 17 minutes. The mean value of the drilling (e.g., milling) performance ranges from 6.61 mm3/s (group 1 [nonexp. + NC]), 9.62 mm3/s (group 2 [exp. w/o NC]), to 10.08 mm3/s (group 3 [exp. + NC]). The relative deviation to the segmented volume amounts to +7.4% (794.3 mm3) for group 1, -39.9% for group 2, and -34% (3,647.0 mm3) for group 3. In the groups with NC guidance of the drill, no damage to a risk structure could be logged. In the group of exp. ear surgeons without NC assistance, one injury to the facial nerve in the petrosal bone phantom occurred. DISCUSSION: The results that follow prove the fundamental feasibility of an NC drill for surgery of the petrosal bone using the example of the simple mastoidectomy in the laboratory test. When using NC, tissue resection is faster, more precise, and has fewer related complications than the same procedure without. The results offer a very promising basis for the introduction of a newly conceived system to the procedure of NC surgery on the petrosal bone. The device configuration used here was originally conceived for NC guidance of a shaver in functional endoscopic sinus surgery. Individual errors will have to be mitigated through the new version of the control unit presently in development. PMID- 17334304 TI - Meta-analysis comparison of open versus percutaneous tracheostomy. AB - OBJECTIVES/HYPOTHESIS: Multiple studies have been performed to characterize differences in complications and cost-effectiveness of open and percutaneous tracheostomy; however, large enough studies have not been performed to determine a clearly superior method. Our primary objective was to compare complication rates of open versus percutaneous tracheostomy in prospective, randomized controlled trials using meta-analysis methodology. Secondary objectives included cost-effectiveness and procedure length analyses. STUDY DESIGN: Meta-analysis. METHODS: From 368 abstracts, 15 prospective, randomized-controlled trials involving nearly 1,000 patients were reviewed to extract basic demographic data in addition to complications, case length, and cost-effectiveness. Pooled odds ratios (OR) with confidence intervals (CI) were calculated in addition to subgroup analyses and meta-regression. RESULTS: Pooled OR revealed statistically significant results against percutaneous tracheostomy for the complication of decannulation/obstruction (OR 2.79, 95% CI 1.29-6.03). There were significantly fewer complications in the percutaneous group with respect to wound infection (0.37, 0.22-0.62) and unfavorable scarring (0.44, 0.23-0.83). There was no statistically significant difference for complications of false passage (2.70, 0.89-8.22), minor hemorrhage (1.09, 0.61-1.97, P = .77), major hemorrhage (0.60, 0.28-1.26), subglottic stenosis (0.59, 0.27-1.29), death (0.70, 0.24-2.01), and overall complications (0.75, 0.56-1.00). However, the overall complications trended toward favoring the percutaneous technique. Percutaneous tracheostomy case length was shorter overall by 4.6 minutes, and costs were less by approximately $456 USD. CONCLUSIONS: Our meta-analysis illustrates there is no clear difference but a trend toward fewer complications in percutaneous techniques. Percutaneous tracheotomies are more cost-effective and provide greater feasibility in terms of bedside capability and nonsurgical operation. PMID- 17334305 TI - CD133, one of the markers of cancer stem cells in Hep-2 cell line. AB - OBJECTIVE: In recent years, a growing body of evidence has been reported that a tumor clone is organized as a hierarchy that originates from rare stem cells. CD133, a cell surface antigen, was identified as a stem cell maker for human leukemia, brain tumors, and prostate cancer. The purpose of this study was to detect the expression of CD133, a putative marker of cancer stem cells in the Hep 2 cell line, and isolate CD133 positive cells to observe their proliferation and differentiation ability in vitro. METHOD: Immunocytochemical staining technology and flow cytometry were used to detect the expression of the putative stem cell marker CD133 in a Hep-2 cell line. The immunomagnetic beads were applied to purify CD133 positive cells. CD133+ tumor cells were cultured in vitro to observe their ability to proliferate and differentiate. RESULTS: Only a small proportion (<5%) of cells in the Hep-2 cell line expressed CD133. CD133+ cells possess a marked capacity for self renewal, extensive proliferation, and mutilineal differentiation potency in vitro. CONCLUSION: CD133 is one of the markers for cancer stem cells in human laryngeal tumors, the Hep-2 cell line. PMID- 17334306 TI - Hearing levels in patients with microtia: correlation with temporal bone malformation. AB - OBJECTIVE: To evaluate the relationship between hearing level and temporal bone abnormalities in patients with microtia. STUDY DESIGN: Retrospective case series study between 1992 and 2004. SETTING: Academic, tertiary care referral medical center. PATIENTS: We evaluated 115 ears of 89 patients (68 males, 21 females; mean age, 11 yr; range, 5-44 yr) with microtia. MAIN OUTCOME MEASURES: Hearing level was examined in patients with microtia. Developmental abnormalities of the temporal bone were evaluated by Jahrsdoerfer's computed tomography (CT) scoring system using high-resolution CT (HRCT) scans of the temporal bone. Temporal bone malformation scores were divided into four subgroups: ossicular development, windows connected to the cochlea, aeration of the middle ear cavity, and facial nerve aberration. Patients were divided into the stenosis and atresia groups on the basis of the appearance of the external auditory canal (EAC). We also evaluated the relationships between hearing level and four subtotal scores of the HRCT findings in the stenosis and atresia groups. RESULTS: There was no relationship between hearing level and total points of HRCT scoring system or between hearing level and severity of microtia scored by Marx classification. With regard to subtotal points related to ossicles (4 points), the hearing level in ears with low scores (<2) (64.7 +/- 1.6 dB) was significantly different (P = .03) from that in ears with high scores (> or =2) (54.0 +/- 2.8 dB) in the stenosis group. In the atresia group, the hearing level was 64.3 +/- 2.2 dB in ears with low scores and 62.3 +/- 1.1 in ears with high scores (P > .5). As for subtotal points related to the windows connected to cochlea (2 points), the hearing level was 64.8 +/- 2.6 dB in ears with low scores (0) and 55.9 +/- 2.4 dB in ears with high scores (> = 1) in the stenosis group. In the atresia group, the hearing level was 67.7 +/- 2.3 dB in ears with low scores and 61.5 +/- 1.0 in ears with high scores. There was significant difference between ears with low and high scores in the stenosis group (P = .03) and atresia group (P = .009). There was no significant difference between ears with low and high scores with respect to the subtotal points related to aeration of the middle ear cavity and aberration of the facial nerve. CONCLUSION: The hearing level in microtic ears correlated with the formation of oval/round windows and ossicular development but not with the degree of middle ear aeration, facial nerve aberration, or severity of microtia. The hearing level can also serve as an indictor, such as the HRCT findings, to determine whether a subject's hearing will likely improve after reconstructive surgery. PMID- 17334307 TI - No negative outcomes of childhood middle ear disease in adulthood. AB - OBJECTIVES/HYPOTHESIS: To test the hypothesis that childhood middle-ear disease may have disadvantageous long-term psychosocial consequences in adulthood. STUDY DESIGN: Prospective, longitudinal study of a general-population birth cohort. METHODS: One thousand thirty-seven people born in 1972/73 were studied from birth to age 26 when 1,019 (96% of survivors) were followed up. Childhood otitis media was assessed, and effects of it have previously been observed in childhood and adolescence. We considered outcome measures that were plausible adult counterparts of the childhood constructs shown to be impaired by otitis media: socioeconomic status, employment status, educational outcomes, personality, mental health, antisocial and criminal behavior, and subjective ratings of personal health (SF-36). RESULTS: No outcome measure was predicted by severity of childhood otitis media. CONCLUSIONS: Adult psychological and socioeconomic outcomes are not related to childhood otitis media when appropriate treatment is available. PMID- 17334308 TI - Quality of life in laryngopharyngeal reflux patients. AB - OBJECTIVES: To evaluate and compare quality of life (QL) parameters in patients with laryngopharyngeal reflux (LPR) versus healthy controls, to determine the impact of clinical signs to QL, and to assess changes in QL parameters after treatment. STUDY DESIGN: Prospective, open, clinical study. MATERIAL AND METHODS: One hundred outpatients with LPR and 109 healthy voice controls were enrolled. LPR patients underwent endoscopy and received omeprazole for 3 months. Results of endoscopy revealed 79 patients without esophagitis and 21 with, giving two subgroups of LPR patients. QL was evaluated using voice handicap index (VHI), hospital anxiety and depression scale, disability in social activities, and well being in general (W-BVAS). RESULTS: The mean scores for total VHI and functional, physical, and emotional functioning domain subscales were found to be significantly higher in LPR patients versus controls (P < .0001), with no difference among LPR subgroups. Abnormal anxiety was one third in both LPR subgroups versus 6.4% of controls (P < .001). Both LPR subgroups patients had significantly reduced social activities and significantly lower mean W-BVAS score than controls. LPR symptoms had a significant relation with all tested QL parameters, whereas laryngoscopic findings had a significant relation with VHI and W-BVAS only. All mean QL parameters scores improved after 3-month omeprazole treatment. CONCLUSIONS: QL in LPR patients with or without esophagitis is impaired significantly in many aspects. Impairment of QL is more associated with symptoms than laryngoscopic findings. Treatment with omeprazole significantly improved QL in both LPR subgroups patients. PMID- 17334309 TI - Microvascular flap reconstruction by otolaryngologists: prevalence, postoperative care, and monitoring techniques. AB - BACKGROUND/OBJECTIVES: Microvascular "free flap" transplants have become the preferred method of reconstruction for a great variety of complicated head and neck defects. As recently as 10 years ago, having a microvascular surgeon within a department of otolaryngology was the exception rather than the rule, whereas it is our impression that today most academic programs have one or more microvascularly trained head and neck surgeons. Among microvascular surgeons, postoperative care and management regimens vary greatly. Through informal conversations, we discerned that some surgeons take a very aggressive approach to monitoring, perhaps including prolonged stays in an intensive care setting with implanted Doppler devices to monitor flap blood flow and intravenous administration of dextran or other pharmaceutical projects. Others report that patients are quickly discharged from the hospital after just aspirin and subcutaneous heparin for a few days. Some physicians perform "flap checks" hourly, whereas others have residents check only once daily. DESIGN/METHODS: We surveyed academic otolaryngology-head and neck surgery departments that sponsor residency programs in the United States to 1) determine the prevalence of microvascular trained otolaryngologists within training programs and 2) assess variations in postoperative and monitoring regimens. RESULTS: We found that on average, 12.2% of otolaryngologists per department perform free flap transplants, and 71.6% of microvascular trained surgeons continue to do free flaps. The surgeons self reported a 96.4% average success rate and a 6.88% return rate to the operating room for complications. Monitoring methods used included flap color (used by 79.4% of surgeons), Doppler signal (79.4%), pin prick and bleeding rate (67.6%), capillary refill (61.8%), skin surface temperature (11.8%), and implanted Doppler (8.8%). Anticoagulants used included aspirin (used by 76.5% of microvascular surgeons), low-molecular-weight dextran (35.3%), and subcutaneous heparin (26.5%). CONCLUSIONS: Microvascular training has become commonplace in otolaryngology-head and neck surgery training programs, with more than one in eight of these academic physicians reporting microvascular training. There was no self-reported difference in flap failure rates on the basis of postoperative care and monitoring regimen. The results of this survey suggest that a simplified consensus postoperative regimen can be recommended. PMID- 17334310 TI - Effects of fibrin glue on nasal septal tissues. AB - OBJECTIVES: To investigate the changes in adult rabbit nasal septal tissues after application of fibrin glue during septoplasty. STUDY DESIGN: Preclinical animal study. METHODS: Nineteen adult albino Vienna rabbits were included in the study. Rabbits were randomly divided into study (n = 14) and control groups (n = 5). The study group was subsequently divided into two subgroups with seven rabbits in each group to investigate short- and long-term effects of fibrin glue. After raising the mucoperichondrial flap on one side of the septum, fibrin glue was used to fix the mucoperichondrial flap over the septal cartilage. Rabbits were killed 3 weeks and 6 weeks after septoplasty. Samples from the excised nasal septa underwent routine tissue procedure for histopathologic investigation. RESULTS: Both short-term and long-term results were compared with the control group and with each other. There was a significant difference regarding mucosal inflammation and cartilaginous damage between groups. A significant difference was found between groups in terms of loss of cilia, loss of goblet cells, the presence and degree of fibrosis. Loss of cartilage was significantly different between groups. In comparing the thickness of the mucosa, thickness of the perichondrium, and thickness of cartilage, there were significant differences between groups. CONCLUSION: Our results demonstrate that fibrin glue causes distinctive inflammation, creates mucosal damage, increases mucosal thickness, decreases perichondrial thickness and cartilaginous thickness, and causes segmental cartilage loss in rabbits. Further comparative clinical investigations are required to assess the clinical efficacy of fibrin glue in nasal septal surgery in humans. PMID- 17334311 TI - Tracheal regeneration after partial resection: a tissue engineering approach. AB - OBJECTIVES: The aims of this study are to investigate the efficiency of a tissue engineering approach to partial tracheal reconstruction and to improve epithelialization of the reconstructed trachea. The trachea must be resected in some cases of cancer or trauma. Various restructuring techniques are used, with no consensus on the best approach. Two problems that arise when treating tracheal defects by conventional techniques are an inability to regenerate ciliated epithelium at the reconstructed site and having to perform multiple procedures to achieve the desired repair. This study is designed to address these problems. STUDY DESIGN: Preliminary, an animal experiment. METHODS: Surgery was performed on five adult beagles under anesthesia. After the making of a longitudinal cervical skin incision, the trachea was exposed and a circular defect created. A polypropylene and collagen scaffold preclotted with peripheral blood was inserted to the defect site. Postoperatively, the site was evaluated fiberscopically, histologically, and radiographically. RESULTS: All dogs did well postoperatively. Fiberscopic examination showed that the implanted scaffolds were completely covered with regenerated mucosa with capillaries in all cases. Histologic data showed ciliated epithelium regenerated at the operated site from 1 month postoperatively. Newly formed cartilage was detected in the specimens from 8 to 12 postoperative months. Computed tomography images revealed the fine luminal contour of the regenerated site. CONCLUSIONS: Good epithelial regeneration was observed after repair of a round tracheal resection using a simple tissue engineering technique, making the technique a good substitute for conventional approaches to tracheal reconstruction in patients with cancer or trauma. PMID- 17334312 TI - Quality of life 17 to 20 years after uvulopalatopharyngoplasty. AB - OBJECTIVES: To study the long-term quality of life outcomes of a group of unselected patients for the long-term effects of uvulopalatopharyngoplasty (UPPP). STUDY DESIGN: Retrospective chart review and telephone survey. METHODS: Forty-nine patients who underwent UPPP between July 1980 and July 1983 and who had their medical records were reviewed and were asked to grade on a visual analogue scale (VAS) the clinical benefits and complications of UPPP after the surgery. RESULTS: Forty-three (87.8%) males and six (12.2%) female patients were studied. Improvement in snoring, excessive daytime somnolence, and nocturnal arousals were seen after UPPP with decreased effectiveness after time. The most common complication of UPPP was velopharyngeal insufficiency (VPI) (28.5%); however, dry throat and swallowing difficulty tended to be more severe in those patients who had them. No correlation between the snoring and VPI VAS grades was observed. Forty-three patients had a preoperative sleep study and 22 patients a postoperative sleep study. There was lack of correlation between the significant subjective clinical improvement and their postoperative polysomnography. CONCLUSION: When undertaking UPPP, both subjective and objective benefits should be weighed against the risk of long-term ill effects. Patients should also be warned that the long-term side effects such as VPI, dry throat, and abnormal swallowing sensation might be more common than previously expected. PMID- 17334313 TI - Health-related quality of life in thyroid cancer survivors. AB - OBJECTIVE: The study objective was to study the impact of the diagnosis, treatment, and follow-up of differentiated thyroid cancer (DTC) on the quality of life and related issues in an urban multi-ethnic Asian population. DESIGN: A self administered questionnaire containing the Short Form 36 Health Survey (SF-36) and assessing sociodemographic, disease, and treatment-related status was mailed to patients with DTC. MAIN OUTCOMES: One hundred fifty-two (52.4%) of 290 patients answered the questionnaire. There was a statistically significant decrease in SF 36 scores between thyroid cancer survivors and the general population in all domains except for social functioning (SF). Physical functioning (PF) was worse in those survivors who were aged 50 years or older. Mental health (MH) scores were better in those who had more than 12 years of formal education. Being employed had a positive influence on role physical (RP) and role emotional (RE) scores. Being of Malay/Indian ethnicity strongly correlated with lower scores in bodily pain (BP), SF, RE and MH domains. CONCLUSION: Although most patients with well-differentiated thyroid cancer have near normal life expectancy, our study has shown that there is a significant decrease in their quality of life, especially in the elderly and poorer educated. Returning to work should be encouraged to improve the quality of life in DTC survivors. PMID- 17334314 TI - Hypoxia stimulates inflammatory and fibrotic responses from nasal-polyp derived fibroblasts. AB - OBJECTIVES/HYPOTHESIS: Chronic sinusitis is primarily an inflammatory disorder characterized by hyperplasia of immune cells and sinus tissue. Nasal mucosal swelling or polyps can occlude the sinus ostia, decreasing the level of oxygen available to the sinus tissue. Hypoxia in many diseases results in increased recruitment of inflammatory cells and release of cytokines. The role of hypoxia in chronic sinusitis is unknown. We hypothesized that hypoxia induces production of mediators that recruit cells into the sinus tissue and are involved in remodeling of the nasal mucosa. METHODS: We compared data from unstimulated nasal polyp derived fibroblasts with those cultured in hypoxic (10% O2) and anoxic (0% O2) environments. Changes in mRNA expression and protein levels of cytokines and chemokines were measured along with changes in cellular proliferation. RESULTS: Hypoxic conditions did not change the proliferative capacity of fibroblasts, whereas anoxia led to a 40% reduction in cellular proliferation (P < .05). Hypoxia led to increases in secretion of many cytokines including vascular endothelial growth factor and CCL11. As a marker of remodeling, procollagen and fibronectin production were significantly increased under hypoxic conditions. CONCLUSIONS: Hypoxic conditions present in the sinus tissue could increase production of proinflammatory and remodeling cytokines that contribute to the inflammation observed in sinusitis. Surgical intervention may help decrease inflammation by allowing reoxygenation of the sinus cavity and decrease the hypoxic induction of cytokines and remodeling factors. PMID- 17334315 TI - Viscoelasticity of hyaluronan and nonhyaluronan based vocal fold injectables: implications for mucosal versus muscle use. AB - OBJECTIVES: The purpose of this study was to measure and compare biomechanical properties of commonly used vocal fold injectates Cymetra, Radiesse, Restylane, Hylaform, and one investigational injectate, Carbylan-GSX 5%, to determine suitability for mucosal injection. STUDY DESIGN: Rheologic investigation. METHODS: Oscillatory shear stress was applied to five samples of each injectate using a parallel plate controlled stress rheometer. Shear stress, shear strain, and strain rate associated with the oscillatory shear deformation were computed from the prescribed torque and measured angular velocity; viscoelastic data were obtained on the basis of these functions. Values calculated included elastic shear moduli, viscous moduli, and dynamic viscosity as a function of oscillatory frequency (0.01-150 Hz). RESULTS: Elastic moduli for all samples increased as the frequency increased. Hyaluronan based materials were all comparable with each other and at least an order of magnitude lower than the stiffer and more viscous Cymetra and Radiesse. Carbylan-GSX 5% was found to have almost identical values to Hylaform with the exception of its mean viscosity, which was noticeably lower. CONCLUSIONS: Hyaluronan based biomaterials offer less resistance to flow and stiffness and may be better suited for injections into the mucosa, whereas Cymetra and Radiesse appear to be appropriate for injections into muscle. Viscoelastic properties of Hylaform and Carbylan-GSX 5% were found to most resemble that of the human vocal fold mucosa. PMID- 17334316 TI - Effects of ciprofloxacin-dexamethasone on myringotomy wound healing. AB - OBJECTIVE: To evaluate the effects of the ciprofloxacin-dexamethasone (CDX) combination ototopical treatment after myringotomy on tympanic membrane (TM) healing in ears with eustachian tube obstruction (ETO) and unobstructed ears. STUDY DESIGN: Prospective, randomized, masked, controlled. METHODS: ETO was created in the left ear of 30 rats to induce a model of otitis media with effusion (OME). After 3 weeks, bilateral myringotomy was performed (day 0). Animals were randomized into three groups to receive no treatment or bilateral once daily ototopical treatment with balanced salt solution (BSS, vehicle) or CDX for 13 days. Bilateral otomicroscopy was performed on days 7, 14, and 28. On day 14, five randomly selected animals per group were humanely euthanized and the TM harvested for histology. Three additional rats provided normal negative control ears for histologic comparisons. RESULTS: On day 14, TM perforation healing rates were 100% in all ears of untreated and BSS-treated animals, 89% (8/9) in CDX treated obstructed ears, and 30% (3/10) in CDX-treated unobstructed ears (P < .05 vs. BSS). On day 28, 100% (5/5) of the CDX-treated unobstructed ears and 80% (4/5) of the CDX-treated obstructed ears were healed. Histology showed initial TM thickening postmyringotomy in all ears but no significant qualitative differences between groups on day 28. CONCLUSION: Myringotomy healing was transiently modulated by treatment with CDX but proceeded normally after CDX discontinuation. This early modulation might enhance middle ear drainage and middle ear concentrations of CDX when tympanostomy tube surgery is performed in patients with active OME and ETO, thus potentially reducing otorrhea and preventing or treating infection. It would not be expected to increase the risk of premature tube extrusion or adversely affect normal healing of the TM after usual spontaneous extrusion. PMID- 17334317 TI - Repetitive transcranial magnetic stimulation for tinnitus: a pilot study. AB - OBJECTIVES/HYPOTHESIS: Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to alleviate tinnitus perception, presumably by inhibiting cortical activity associated with tinnitus. We conducted a pilot study to assess effectiveness of neuronavigated rTMS and its effects on attentional deficits and cortical asymmetry in four patients with chronic tinnitus using objective and subjective measures and employing an optimization technique refined in our laboratory. STUDY DESIGN: Randomized, placebo-controlled (sham stimulation) crossover study. METHODS: Patients received 5 consecutive days of active, low frequency rTMS or sham treatment (using a 45-degree coil-tilt method) before crossing over. Subjective tinnitus was assessed at baseline, after each treatment, and 4 weeks later. Positron emission tomography/computed tomography (PET/CT) scans were obtained at baseline and immediately after active treatment to examine change in cortical asymmetry. Attentional vigilance was assessed at baseline and after each treatment using a simple reaction time test. RESULTS: All patients had a response to active (but not sham) rTMS, as indicated by their best tinnitus ratings; however, tinnitus returned in all patients by 4 weeks after active treatment. All patients had reduced cortical activity visualized on PET immediately after active rTMS. Mean reaction time improved (P < .05) after active but not sham rTMS. CONCLUSIONS: rTMS is a promising treatment modality that can transiently diminish tinnitus in some individuals, but further trials are needed to determine the optimal techniques required to achieve a lasting response. It is unclear whether the improved reaction times were caused by tinnitus reduction or a general effect of rTMS. PET/CT scans immediately after treatment suggest that improvement may be related to reduction of cortical asymmetry associated with tinnitus. PMID- 17334318 TI - Noise exposure of the inner ear during drilling a cochleostomy for cochlear implantation. AB - OBJECTIVES: Inserting an electrode array into the cochlea may cause inner ear trauma, which has to be minimized, particularly in cochlear implant patients with substantial residual hearing. Another potential inner ear trauma has, to a large extent, been neglected so far: the acoustic trauma that can occur during cochleostomy using different techniques. In this study, the noise exposure of the inner ear during the drilling procedure was re-evaluated. In experiments on temporal bones, quantitative measurements of sound pressure level (SPL) were carried out while a cochleostomy for cochlear implantation was drilled. STUDY DESIGN: Experimental study. MATERIALS AND METHODS: Acoustic measurements during different drilling procedures were carried out on four human temporal bone preparations equipped with microphones attached to the round window. Special calibrations were carried out, which allowed determination of SPLs affecting the cochlea during the drilling procedure. RESULTS: The highest SPLs measured on the cochlea were recorded when a still-intact endosteal membrane was touched by the burr. The SPL exceeded 130 dB and reached a level almost comparable with the situation when the ossicular chain is touched by a running burr. CONCLUSIONS: In the drilling procedure for a cochleostomy, the inner ear may be affected by very high SPLs, particularly if the endosteal membrane is left intact and comes into contact with the running burr. Of course, the resulting SPLs depend on the drilling speed and the size and characteristics of the burr (larger burrs cause higher SPLs); however, we are of the opinion that the cochlear function is at risk, anyway, if special precaution is not exercised. Even when working with reduced drilling speed, the surgeon should be aware of the high risk in the form of an acoustic trauma, which may endanger residual hearing. Recommendations in terms of "soft surgery" are given in the paper (e.g., the use of microhooks instead of a drill to remove the very last shell of bone covering the cochlea). PMID- 17334319 TI - Functional optical hemodynamic imaging of the olfactory cortex. AB - OBJECTIVE: We used multichannel near-infrared spectroscopy (MNIRS) to monitor the activity of the frontal cortex as mirrored by hemodynamic responses subjected to olfactory stimulation. The aim of this study was to clarify the functional brain imaging of olfactory activity. STUDY DESIGN: Prospective study. METHODS: This study was conducted on eight healthy subjects aged from 22 to 39 years (4 men and 4 women; mean age, 28.8 yr). We used a 22-channel near-infrared spectroscopy device with eight light-incident fibers and seven detector fibers, each with an interoptode distance of 2.5 cm on the frontal region. Olfactory stimulation consisted of five repetitions, each lasting 5 seconds and followed by a 55 seconds rest period. Isovaleric acid was used as odor stimulation, and saline was used as a control. We measured the changes in concentrations of oxyhemoglobin [oxyHb], deoxyhemoglobin [deoxyHb], and total hemoglobin [totalHb] from prebaseline values. Furthermore, we divided the frontal cortex into four areas (right upper, left upper, right lower, left lower) and investigated the activity in each area. RESULTS: Isovaleric acid caused changes, especially in the lower area, but saline caused no changes. [oxyHb] and [totalHb] increased after odor stimulation, but [deoxyHb] did not change. These active areas may be related to the orbitofrontal cortex, corresponding to olfactory cortices. CONCLUSION: This study has shown that MNIRS enables evaluation of changes in hemodynamics related to brain activity by olfactory stimulation. PMID- 17334320 TI - Genetic and acquired prothrombotic risk factors and sudden hearing loss. AB - OBJECTIVES: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a frequently encountered condition, and various pathogenetic mechanisms have been hypothesized, such as viral infections, autoimmune processes, and ischemic events; however, whatever the cause, impaired cochlear perfusion appears to be the most important event. A number of inherited prothrombotic risk factors and their related genetic alterations have recently been correlated with vascular disorders. METHODS: To investigate the mechanisms of vascular thrombosis of the inner ear leading to sudden HL, we examined 100 patients with SSNHL for the presence of acquired or inherited prothrombotic risk factors and 200 healthy volunteers as controls. All of the subjects underwent hematologic examinations, including MTHFR C677T and A1298C, prothrombin G20210A, platelet GlyIIIaA1/A2, V Leiden G1691A genotyping, fibrinogenemia, cholesterolemia, homocystinemia, and folatemia. Genomic DNA was isolated from peripheral blood leukocytes using standard methods, and gene mutations were investigated using a LightCycler DNA analyser and polymerase chain reaction. RESULTS: A statistically significant association was found between SSNHL and the MTHFR C677T/A1298C polymorphisms, the prothrombin G20210A transition, and the platelet GlyIIIa and V Leiden G1691A mutations. Furthermore, the SSNHL patients had significantly higher levels of fibrinogenemia, cholesterolemia, and homocystinemia and lower levels of folatemia than the controls (P < .0001). CONCLUSIONS: The association between inherited and acquired prothrombotic factors and sudden HL suggests that the microvascular impairment causing SSNHL may be caused by a multifactorial mechanism. All patients with ISSNHL should undergo a comprehensive hematologic investigation of inherited and acquired prothrombotic factors, including MTHFR polymorphisms, the prothrombin transition, and the platelet and V Leiden mutations, to identify a subset of patients at high risk of recurrent HL. PMID- 17334321 TI - New perspectives for middle ear implants: first results in otosclerosis with mixed hearing loss. AB - Middle ear implantation is an efficient procedure to restore moderate to severe sensorineural hearing loss (HL) in selected patients. Implantation of such devices requires ossicular chain integrity. Patients suffering from otosclerosis with mixed HL should be eligible for this treatment after stapes surgery with air bone gap closure. To address this issue, we report four cases of middle ear implantation after or during stapes surgery. Results and complications obtained with Vibrant SoundBridge, MedEl and Middle Ear Transducer, Otologics are reported. Audiologic results were similar to those obtained in cases of sensorineural HL. One case of postoperative labyrinthitis was observed. PMID- 17334322 TI - Anterior inferior cerebellar artery infarction presenting with sudden hearing loss and vertigo. AB - A peripheral origin is typically contemplated in a patient presenting with sudden hearing loss (HL) and dizziness without other neurologic manifestations. Although symptoms of anterior inferior cerebellar artery (AICA) infarction include sudden HL and vertigo, the clinical picture usually shows ipsilateral facial anesthesia or paralysis, Horner's syndrome, contralateral body anesthesia, or cerebellar dysmetria. A 68-year-old female patient developed sudden HL in the right ear and vertigo. A left-beating horizontal torsional nystagmus was observed, and caloric weakness in the right side was noted. Diffusion- and T2-weighted magnetic resonance imaging revealed cerebellar infarction in the right AICA territory. AICA infarction may present without obvious neurologic deficits, and an imaging study is advised in patients at high risk for vascular accidents. PMID- 17334323 TI - Tympanostomy T-tube introducer: a simple technique using a Zoellner suction tube. PMID- 17334324 TI - In reference to: "Cervical metastasis from squamous cell carcinoma of the maxillary alveolus and hard palate.". PMID- 17334326 TI - Chronic rhinosinusitis and fatigue: a relationship that requires continuing documentation. PMID- 17334329 TI - Meeting report: death and differentiation in erice. PMID- 17334328 TI - In situ end labelling of DNA to detect apoptotic cell death in a variety of human tumours. AB - The present studies illustrate clinical applications of in situ end labelling (ISEL) of DNA to detect apoptosis in a variety of human malignancies including myelodysplastic syndromes (MDS, n=10), non-Hodgkin's lymphoma (NHL, n=10), head and neck cancer (n = 3), breast cancer (n = 1) and cervical cancer (n = 1). These studies also describe a new in situ double labelling technique to detect apoptosis and proliferation (S-phase cells) simultaneously in the same section of plastic embedded tissue. In vivo intravenous infusions of thymidine analogues (i.e. bromodeoxyuridine (BrdU) and/or iododeoxyuridine (IUdR)) followed by their detection with a specific monoclonal antibody in a plastic embedded biopsy, combined with ISEL in the same section, facilitated simultaneous estimations of apoptosis and proliferation. The most salient finding of these studies was excessive apoptosis in MDS including the cells in S-phase as indicated by uniquely double labelled cells in their bone marrow biopsies. On the other hand, a very low degree of apoptosis was observed in NHL and other solid tumours. Moreover, the solid tumours exhibited definite compartments of apoptosis and proliferation. Further experiments are underway to confirm these findings in a larger study in order to design appropriate therapeutic modalities for these disorders. PMID- 17334330 TI - Cellular and molecular mechanisms of abnormal calcification following ischemia reperfusion injury in human liver transplantation. AB - Recent studies suggest a possible link between calcification and ischemia reperfusion injury following liver transplantation. Histological staining, immunolabeling, and biochemical and electron microscopy analyses were applied to assess the possible mechanism(s) of calcification in liver tissue. Although light microscopy studies did not reveal the presence of large necrotic or apoptotic areas, electron microscopy showed the presence of membrane-bound vacuolar structures in hepatocytes, indicative of cell damage. Myofibroblasts were abundant in regions surrounding and within calcification. In these precalcified and calcified areas, myofibroblasts expressed bone-specific matrix proteins, such as osteopontin, type 1 collagen and bone sialoprotein. In addition, transforming growth factor beta (TGFbeta)-1 and BMP2, two growth factors implicated in osteoblast differentiation, and Runx2 and Msx2, two transcription factors targets of TGFbeta-1 and BMP2, were also expressed in these myofibroblasts. These data suggest that liver calcification following transplantation may be a consequence of precipitation of hydroxylapatite emanating from necrotic or apoptotic hepatocytes associated with proliferation of myofibroblasts expressing bone specific matrix proteins. PMID- 17334331 TI - Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization. AB - Ossifying fibroma and fibrous dysplasia of the jaw are maxillofacial fibro osseous lesions that should be distinguished each other by a pathologist because they show distinct patterns of disease progression. However, both lesions often show similar histological and radiological features, making distinction between the two a diagnostic dilemma. In this study, we performed immunological and molecular analyses of five ossifying fibromas, four cases of extragnathic fibrous dysplasia, and five cases of gnathic fibrous dysplasia with typical histological and radiographic features. First, we examined the difference between fibrous dysplasia and ossifying fibroma in the expression of Runx2 (which determined osteogenic differentiation from mesenchymal stem cells) and other osteogenic markers. Fibroblastic cells in fibrous dysplasia and ossifying fibroma showed strong Runx2 expression in the nucleus. The bone matrices of both lesions showed similar expression patterns for all markers tested except for osteocalcin. Immunoreactivity for osteocalcin was strong throughout calcified regions in fibrous dysplasia, but weak in ossifying fibroma lesions. Second, we performed PCR analysis with peptide nucleic acid (PNA) for mutations at the Arg(201) codon of the alpha subunit of the stimulatory G protein gene (GNAS), which has reported to be a marker for extragnathic fibrous dysplasia. All nine cases of extragnathic or gnathic fibrous dysplasia were positive for this mutation. On the other hand, none of the five cases of ossifying fibroma showed the mutation. These findings indicate that although fibrous dysplasia and ossifying fibroma are similar disease entities, especially in the demonstration of the osteogenic lineage in stromal fibroblast-like cells, they show distinct differences that can be revealed by immunohistochemical detection of osteocalcin expression. Furthermore, PCR analysis with PNA for GNAS mutations at the Arg(201) codon is a useful method to differentiate between fibrous dysplasia and ossifying fibroma. PMID- 17334332 TI - Differentiating Ewing's sarcoma from other round blue cell tumors using a RT-PCR translocation panel on formalin-fixed paraffin-embedded tissues. AB - Ewing's sarcoma is a common malignancy of bone and soft tissue that occurs most often in children and young adults. Differentiating Ewing's sarcoma from other round blue cell tumors can be a diagnostic challenge because of their similarity in histology and clinical presentation. Thus, ancillary molecular tests for detecting disease-defining translocations are important for confirming the diagnosis. We analyzed 65 round blue cell tumors, including 53 Ewing's sarcoma samples from 50 unique cases. Samples were processed for RNA from archived formalin-fixed paraffin-embedded tissue blocks. Real-time RT-PCR assays specific for Ewing's sarcoma (EWS-FLI1, EWS-ERG, EWS-ETV1, EWS-ETV4, and EWS-FEV), synovial sarcoma (SYT-SSX1 and SYT-SSX2), and rhabdomyosarcoma (PAX3-FKHR and PAX7-FKHR) were tested across the samples. The translocation panel had a sensitivity of 81% (43 out of 53 samples) for diagnosing Ewing's sarcoma when using the histological criteria as the 'gold' standard. None of the Ewing's specific translocations were found in the non-Ewing's samples (100% specificity). Of the 43 samples with translocations detected, 26 (60%) had an EWS-FLI1 type 1 translocation, 13 (30%) had an EWS-FLI1 type 2 translocation, 3 (7%) had an EWS ERG translocation, 1 had an EWS-ETV1 translocation, and 1 sample had both an EWS FLI1 type 1 and type 2 translocation. Our real-time RT-PCR assay for detecting sarcoma translocations has high sensitivity and specificity for Ewing's sarcoma and has clinical utility in differentiating small round blue cell tumors in the clinical lab. PMID- 17334333 TI - Rheumatology in the Asia Pacific region--opportunities and challenges. PMID- 17334334 TI - Unresolved issue: should patients with RA and a history of malignancy receive anti-TNF therapy? PMID- 17334335 TI - The health assessment questionnaire in routine clinical practice. PMID- 17334336 TI - The antiphospholipid syndrome as a disorder initiated by inflammation: implications for the therapy of pregnant patients. AB - Arterial thrombosis, venous thrombosis and morbidity during pregnancy, or a combination of these events, are clinical outcomes associated with antiphospholipid antibodies produced by patients with antiphospholipid syndrome (APS). Our understanding of the etiology and pathogenesis of the syndrome is limited, but it has generally been considered a thrombophilic disease and treatment has focused on anticoagulation. Agents such as aspirin and heparin, administered alone or in combination, are empirical treatments that are used in the management of obstetric patients with APS. Clinical features, such as heart valve abnormalities, thrombocytopenia and livedo reticularis, suggest multiple pathogenic mechanisms and provide other therapeutic targets. Findings from research in animal models of APS challenge the dogma that this syndrome is a noninflammatory, thrombotic disease and provide evidence that activation of complement is crucial for complications in pregnancy. These studies, in addition to evidence of inflammatory-mediated tissue damage in placentae of patients with APS, suggest that therapy should also be directed towards preventing inflammation. This Review describes the potential mechanisms of tissue injury by antiphospholipid antibodies, the management of pregnant patients with APS and how heparin therapy might inhibit the pathogenic mediators of disease. PMID- 17334337 TI - Behcet's syndrome: disease manifestations, management, and advances in treatment. AB - The acne lesions characteristic of Behcet's syndrome are not sterile and are commonly observed in combination with arthritis. The two main nodular skin lesions--superficial thrombophlebitis and erythema nodosum--are equally frequent, and rather difficult to distinguish. Superficial thrombophlebitis is usually observed in combination with thrombosis in large veins, and thrombosis of the large veins usually clusters with dural sinus thrombi, which make up approximately 20% of all central nervous system (CNS) lesions of Behcet's syndrome. The remaining CNS lesions are parenchymal, mainly located in the brainstem, and associated with a graver prognosis than dural sinus thrombi. The presence of clinical clusters indicates that there are at least two pathogenetic pathways in Behcet's syndrome: a reactive arthritis pathway and a thrombophilia pathway. Research into the pathogenesis of Behcet's syndrome has shown that the most consistent genetic marker of Behcet's syndrome is HLA-B51; however, the genetic association of this true-to-form 'complex' disorder with HLA-B51 is only 20%, and a whole-genome study showed associations with 16 different loci. The severity of Behcet's syndrome and the mortality associated with it tend to decrease with time, and there is no associated increase in incidence of atherosclerosis. Although treatment of skin-mucosa manifestations, eye disease and pulmonary artery aneurysms has improved significantly in the past decades, the treatment of CNS lesions and thrombophilia are still problematic. PMID- 17334338 TI - Drug insight: Anti-tumor necrosis factor therapy for inflammatory arthropathies during reproduction, pregnancy and lactation. AB - Tumor necrosis factor (TNF) antagonists are widely used to reduce disease activity and joint damage, and to improve health-related quality of life in patients suffering from rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. To date, no increased risk of embryotoxicity or teratogenicity, or adverse pregnancy outcome (such as birth defects, premature birth, and low birth weight) has been reported in patients with inflammatory arthropathies treated with anti-TNF therapy, compared with the general population. However, the available data are limited, and methotrexate, which is commonly used in combination with anti-TNF drugs, is teratogenic. Until more data are available, no firm conclusions can be reached regarding the safety of anti TNF therapy in pregnancy. Nevertheless, in selected cases where there is high disease activity, anti-TNF therapy might be recommended, depending on the results of individual risk-benefit analyses. Fully informed consent from the mother is needed in such cases. Anti-TNF agents are not usually used during lactation, although the risk of toxicity is probably negligible. PMID- 17334339 TI - Mechanisms of disease: Molecular insights into aseptic loosening of orthopedic implants. AB - Despite the success of treating rheumatic disorders with biologic therapies, joint replacement surgery still remains the final treatment option in many cases. Approximately 1.5 million joint arthroplastic operations are performed annually worldwide. Implant failure due to massive bone loss and aseptic loosening of prostheses, however, is a major complication of joint replacement, which can lead to high socioeconomic burdens both for the individual patient and for health-care systems. To date, there is no approved drug therapy to prevent or inhibit periprosthetic osteolysis, and aseptic loosening of prostheses can only be overcome by surgical revision. Research during the past decade, however, has unravelled much of the pathogenesis of aseptic prosthesis loosening and preclinical studies have identified potential targets for pharmaceutical treatments. This article highlights the importance of a cooperative interaction between rheumatologists and orthopedic surgeons, and presents novel insights into the molecular mechanisms behind aseptic loosening of prostheses. In addition, we outline potential perspectives for the development of future therapeutic strategies for this devastating complication. PMID- 17334340 TI - Mechanisms of disease: Environmental factors in the pathogenesis of rheumatic disease. AB - Most rheumatic diseases are complex disorders for which pathogenetic mechanisms are poorly understood. Nonetheless, increasing evidence suggests that many of these illnesses result from one or more specific environmental exposures in genetically susceptible individuals. Although much progress has been made over the past few decades in advancing our knowledge of the genetics of rheumatic diseases, few studies have assessed environmental features and understanding of which exposures are important in pathogenesis remains limited. In this article, we review the difficulties inherent in deciphering the interacting environmental and genetic risk factors for rheumatic diseases, the current state of knowledge of infectious and noninfectious risk factors, possible mechanisms by which environmental exposures might induce pathologic processes and future directions. The advances in technologies and statistical approaches, development of collaborating consortia and focused resources that have resulted in the explosion of genetic information must now be applied to environmental studies so we can eventually interrupt pathogenesis before the onset of disease and transform the practice of medicine from curative to pre-emptive paradigms. PMID- 17334341 TI - Primer: Demystifying risk--understanding and communicating medical risks. AB - Assessments of risk are a critical part of the practice of evidence-based medicine. Comprehension of various risk measures, such as absolute risk, relative risk, attributable risk, odds ratio, and hazard ratio, is essential to understand the medical literature, and to communicate health risks effectively. Complex risk measures, including number needed to treat and survival estimates that are adjusted for competing risks, are often misunderstood. Communication of these concepts to patients can be a challenge. The patient's perception of risk stems not only from the way risks are stated, but also from family history, personal experiences, cultural norms, and beliefs. A multifaceted approach to risk communication that uses both qualitative and quantitative assessments of risk, and addresses the timing and permanence of risks, is necessary to ensure the patient understands the potential risks. Successful communication involves interaction with the patient to understand the patient's perspective and to aid in personalized decision-making. In the face of uncertainty, making a provisional decision with a plan to review it later can be a good strategy. Verifying the patient's comprehension can help ensure that the decisions reached are informed and acceptable. PMID- 17334342 TI - Pigmented villonodular synovitis with chondroid metaplasia, resembling chondroblastoma of the bone: a report of three cases. AB - We herein describe three cases of pigmented villonodular synovitis with chondroid metaplasia. Two cases involved the temporomandibular joint, whereas the remaining one case occurred in the hip joint. Histologically, the tumors showed a villous pattern and were mainly composed of histiocyte-like cells and scattered osteoclast-like multinucleated giant cells, accompanied by chondroid areas with occasional lace-like calcification. These features resembled those of chondroblastoma of the bone, with the exception of the villous pattern. The histiocyte-like cells showed positive immunoreactivity for CD68, whereas they were negative for S-100 protein. Some of the previously reported cases of chondroblastoma in the temporal bone may have actually been cases of pigmented villonodular synovitis with chondroid metaplasia. When histologically chondroblastoma-like lesions involve the temporal bone or temporomandibular joint, the possibility of pigmented villonodular synovitis with chondroid metaplasia should also be considered, in addition to chondroblastoma of the bone. The correlation between this lesion and synovial chondromatosis remains uncertain. PMID- 17334343 TI - Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. AB - Novel recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, or ETV4 have been recently identified as a common molecular event in prostate cancer development. We comprehensively analyzed the frequency and risk of disease progression for the TMPRSS2 and ETS family genes rearrangements in a cohort of 96 American men surgically treated for clinically localized prostate cancer. Using three break apart (TMPRSS2, ERG, ETV4) and one fusion (TMPRSS:ETV1) fluorescence in situ hybridization (FISH) assays, we identified rearrangements in TMPRSS2, ERG, ETV1, and ETV4 in 65, 55, 2, and 2% of cases, respectively. Overall, 54 and 2% of cases demonstrated TMPRSS2:ERG and TMPRSS2:ETV1 fusions, respectively. As intronic loss of genomic DNA between TMPRSS2 and ERG has been identified as a mechanism of TMPRSS2:ERG fusion, our assays allowed us to detect deletion of the 3' end of TMPRSS2 and the 5' end of ERG in 41 and 39% of cases rearranged for respective genes. Prostate cancers demonstrating TMPRSS2 gene rearrangement were associated with high pathologic stage (P=0.04). Our results confirm that recurrent chromosomal aberrations in TMPRSS2 and/or ETS family members are found in about 70% of prostate cancers. Importantly, we define a novel approach to study these gene fusions and identified cases where TMPRSS2 was rearranged without rearrangement of ERG, ETV1 or ETV4 and cases with ETS family gene rearrangement without TMPRSS2 rearrangement, suggesting that novel 5' and 3' partners may be involved in gene fusions in prostate cancer. PMID- 17334344 TI - Benign extramedullary myeloid proliferations. AB - Extramedullary proliferations of bone marrow elements are infrequently encountered in routine pathology practice. On occasion, they can present diagnostic difficulties when seen in unusual or unanticipated sites. This review serves to cover aspects of underlying embryogenesis of myeloid elements, as well as sites and circumstance of benign proliferations of myeloid elements along with their occasional confusion with neoplastic myeloid proliferations. Benign proliferations associated with hematologic disorders and hematopoietic growth factors are discussed. Immunohistochemical evaluation of myeloid proliferations is considered as well. PMID- 17334345 TI - Prognostic significance of angiogenesis in gastrointestinal stromal tumor. AB - Angiogenesis is important in the growth and metastasis of various kinds of solid tumors. To investigate the potential role of angiogenesis in gastrointestinal stromal tumor (GIST), an immunohistochemical analysis was performed in 95 cases of GISTs for microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression. MVD was evaluated with immunohistochemical staining for CD31. A high level of MVD was significantly correlated with overexpression of VEGF, tumor location (intestine>stomach), tumor size (> or =5 cm), tumor grade (high>intermediate>low grade) (P=<0.0001, 0.0422, 0.0006, 0.0359, respectively). Of the 70 GISTs analyzed, KIT exon 11 mutations were detected in 45 cases (64.3%) and KIT exon 9 mutations in two cases (2.9%). No mutations were found in KIT exons 13 and 17, and platelet-derived growth factor receptor-alpha exons 12 and 18. Interestingly, VEGF expression level was significantly higher in the non-KIT exon 11 mutant group than in the KIT exon 11 mutant group (P=0.0266). In univariate analysis, tumor grade (high grade), tumor size (> or =5 cm), mitotic count (> or =5/50 high-power fields), Ki-67 labeling index (> or =4.6%), MVD (> or =7.0/0.95 mm(2)) and VEGF expression (high) were significantly associated with a shorter period of disease-free survival (P=<0.0001, 0.0199, 0.0055 0.0027, 0.0028 and 0.0302, respectively). In multivariate analysis, tumor grade and MVD were identified as independent worse prognostic factors (P=0.0007, 0.0152, respectively). In conclusion, our results suggest that the evaluation of MVD and VEGF expression is useful for predicting the aggressive biologic behavior of GIST, and that angiogenesis associated with VEGF may play an important role, at least in part, in the progression of GIST. PMID- 17334346 TI - Immunostaining for SYT protein discriminates synovial sarcoma from other soft tissue tumors: analysis of 146 cases. AB - Synovial sarcoma in its classic biphasic form can be distinguished readily from other soft tissue lesions; however, monophasic and poorly differentiated forms are diagnostically more problematic. For this reason, we assessed the efficacy of immunostaining for SYT and SSX1 proteins, the gene products resulting from unique synovial sarcoma translocation, to distinguish synovial sarcoma from other soft tissue lesions. A total number of 146 cases were analyzed, including 47 synovial sarcoma cases (all of which were verified by FISH to have t(X; 18) translocation and SYT-SSX fusion gene) and 99 soft tissue tumors of various types. A polyclonal IgG antibody against SYT was used to stain formalin-fixed paraffin embedded tissues. Forty-one out of 47 (87%) synovial sarcoma displayed strong positive nuclear staining (ranging from 80 to 90% of the tumor cells) for SYT antibody. Nineteen of 99 (19%) non-synovial sarcoma cases showed variable nuclear and cytoplasmic staining with SYT, which ranged from 20 to 60% of tumor nuclei, and included malignant peripheral nerve sheath tumor (5/25), solitary fibrous tumor (2/14), Ewing sarcoma (2/6), low grade fibromyxoid tumor (2/4), extraskeletal mesenchymal chondrosarcoma (2/6), gastrointestinal tumor (4/17), epithelioid sarcoma (2/2). The remaining non-synovial sarcomas were negative. This is the first study demonstrating SYT protein expression in tissue sections of synovial sarcoma. This method could provide an easy, rapid and widely applicable means of assisting in the diagnosis of synovial sarcoma, particularly when material and/or resources are unavailable for PCR or FISH-based testing. However, as variable weak staining for SYT may be encountered in a small percentage of non-synovial sarcoma sarcomas, a positive interpretation should be made only when the staining is strong, nuclear and present in the majority of cells. PMID- 17334347 TI - Micropapillary pattern and grade of stromal invasion in pT1 adenocarcinoma of the lung: usefulness as prognostic factors. AB - Recently, the stromal invasion grading system was proposed for small adenocarcinomas of < or =2.0 cm. The system is based on the presence or absence of a fibrotic focus, and the extent of invasion into the fibrotic focus. Although stromal invasion grading system closely correlated with the prognosis, stromal invasion grade 3, representing stromal invasion into the center of a fibrotic focus, was the largest group of tumors and showed variable prognosis. In this study, we investigated whether stromal invasion grading system could be applied to and validated in pT1 adenocarcinomas as the TNM classification is the most universally used system. Furthermore, we investigated whether stromal invasion grade 3 cases could be subclassified according to the presence and absence of micropapillary pattern. The study included 120 cases of pT1 lung adenocarcinomas, of which 81 (68%) cases were stromal invasion grade 3. Micropapillary pattern was positive in 80% of grade 3 cases. For stromal invasion grade 3 cases, the 5-year survival rate of patients with micropapillary pattern-positive carcinomas was 63%, which was significantly worse than 94% of those with micropapillary pattern negative carcinomas (P=0.0196). The latter was very close to that for patients with stromal invasion grade 0-2 (95%). Moreover, small cluster invasion was observed at sites of stromal invasion significantly more often in micropapillary pattern-positive cases than negative cases. Thus, the stromal invasion grading system is reproducible and correlates with prognosis even in pT1 lung adenocarcinomas. Moreover, among patients with stromal invasion grade 3 carcinomas, favorable prognosis is noted in micropapillary pattern-negative cases. The micropapillary pattern subclassification provides an advantage to the stromal invasion grading system and reconfirms the importance of micropapillary pattern as a prognostic marker. Our study is the first to point to the possible association of micropapillary pattern-positive carcinomas and small cluster invasion. PMID- 17334348 TI - Loss of cell-adhesion molecule complexes in solid pseudopapillary tumor of pancreas. AB - Solid pseudopapillary tumor of pancreas (SPT) is a rare neoplasm that occurs most often in young females with the two distinct features, the 'solid-cystic' gross appearance, and the 'solid-pseudopapillary' microscopic pattern. It has been reported that almost all SPT tumors contain a mutation in the beta-catenin gene; however, the histogenetic origin of this tumor remains largely a mystery. E cadherin is a cell adhesion molecule that links to catenins to form cell adhesion junctions, which is associated with the cytoskeleton formation. In this study, we examined the expression of E-cadherin and beta-catenin from SPT in an attempt to determine the molecular basis for the unusual morphology of this tumor. Nine cases of SPT were retrieved from Surgical Pathologic Archives of three institutions, including one male and eight females. H&E slides of each case were reviewed to confirm the diagnosis. The beta-catenin gene was sequenced in one case. E-cadherin and beta-catenin immunostains, were performed on all nine cases. Sequencing analysis on one case showed a point mutation of the beta-catenin gene, confirming previous findings that almost all SPT tumors contain mutation in the beta-catenin gene. Immunostains showed that, in both solid and pseudopapillary areas, all the tumor cells lost expression of E-cadherin, and beta-catenin nuclear expression was observed in all cases. Our findings suggest that loss of cytoplasmic beta-catenin protein in the cell adhesion complex due to beta-catenin gene mutation, results in instability of the complex, loss of E-cadherin in cell membrane, and eventually dissociation of the tumor cells to form the pseudopapillary pattern. PMID- 17334349 TI - Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma. AB - Synovial Sarcoma consistently harbors t(X;18) resulting in SS18-SSX1, SS18-SSX2 and rarely SS18-SSX4 fusion transcripts. Of 328 cases included in our study, synovial sarcoma was either the primary diagnosis or was very high in the differential diagnosis in 134 cases: of these, amplifiable cDNA was obtained from 131. SS18-SSX fusion products were found in 126 (96%) cases (74 SS18-SSX1, 52 SS18-SSX2), using quantitative and 120 by conventional reverse transcriptase polymerase chain reaction (RT-PCR). One hundred and one cases in a tissue microarray, analyzed by fluorescence in situ hybridization (FISH), revealed that 87 (86%) showed SS18 rearrangement: four RT-PCR positive cases, reported as negative for FISH, showed loss of one spectrum green signal, and 15 cases had multiple copies of the SS18 gene: both findings are potentially problematic when interpreting results. One of three cases, not analyzed by RT-PCR reaction owing to poor quality RNA, was positive by FISH. SS18-SSX1 was present in 56 monophasic and 18 biphasic synovial sarcoma: SS18-SSX2 was detected in 41 monophasic and 11 biphasic synovial sarcoma. Poorly differentiated areas were identified in 44 cases (31%). There was no statistically significant association between biphasic, monophasic and fusion type. Five cases were negative for SS18 rearrangement by all methods, three of which were pleural-sited neoplasms. Following clinical input, a diagnosis of mesothelioma was favored in one case, a sarcoma, not otherwise specified in another and a solitary fibrous tumor in the third case. The possibility of a malignant peripheral nerve sheath tumor could not be excluded in the other two cases. We concluded that the employment of a combination of molecular approaches is a powerful aid to diagnosing synovial sarcoma giving at least 96% sensitivity and 100% specificity but results must be interpreted in the light of other modalities such as clinical findings and immunohistochemical data. PMID- 17334350 TI - Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer. AB - Tumours arising in BRCA1 mutation carriers and sporadic basal-like breast carcinomas have similar phenotypic, immunohistochemical and clinical characteristics. SOX2 is an embryonic transcription factor located at chromosome 3q, a region frequently gained in sporadic basal-like and BRCA1 germline mutated tumours. The aim of the study was to establish whether sox2 expression was related to basal-like sporadic breast tumours. Two hundred and twenty-six sporadic node-negative invasive breast carcinomas were immunohistochemically analysed for oestrogen receptor (ER), progesterone receptor (PR), CK5/6, EGFR, vimentin, HER2, ki67, p53 and sox2 using tissue microarrays. Tumours were considered to have basal-like phenotype if they were ER/HER2-negative and CK5/6 and/or EGFR-positive. Thirty cases of this series (13.7%) displayed a basal-like phenotype. Sox2 expression was observed in 16.7% of cases and was significantly more frequently expressed in basal-like breast carcinomas (43.3% in basal-like, 10.6% in luminal and 13.3% in HER2+ tumours, P<0.001). Moreover, Sox2 showed a statistically significant inverse association with ER and PR (P=0.001 and 0.017, respectively) and direct association with CK5/6, EGFR and vimentin (P=0.022, 0.005 and <0.001, respectively). Sox2 is preferentially expressed in tumours with basal-like phenotype and may play a role in defining their less differentiated/'stem cell' phenotypic characteristics. PMID- 17334351 TI - A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis. AB - Prostate cancer is the most commonly diagnosed cancer among men in the United States. Recently, fusion of TMPRSS2 with ETS family oncogenic transcription factors has been identified as a common molecular alteration in prostate cancer, where most often the rearrangement places ERG under the androgen-regulated transcriptional control of TMPRSS2. Here, we carried out rapid amplification of cDNA ends (RACE) on a prostate cancer specimen carrying an atypical aberration discovered by array-based comparative genomic hybridization (array CGH), suggesting an alternative fusion partner of ERG. We identified novel transcribed sequences fused to ERG, mapping 4 kb upstream of the TMPRSS2 start site. The sequences derive from an apparent second TMPRSS2 isoform, which we found also expressed in some prostate tumors, suggesting similar androgen-regulated control. In a reverse transcription-polymerase chain reaction (RT-PCR)-based survey of 63 prostate tumor specimens (54 primary and nine lymph node metastases), 44 (70%) cases expressed either the known or novel variant TMPRSS2-ERG fusion, 28 (44%) expressed both, 10 (16%) expressed only the known, and notably six (10%) expressed only the variant isoform fusion. In this specimen set, the presence of a TMPRSS2-ERG fusion showed no statistical association with tumor stage, Gleason grade or recurrence-free survival. Nonetheless, the discovery of a novel variant TMPRSS2 isoform-ERG fusion adds to the characterization of ETS-family rearrangements in prostate cancer, and has important implications for the accurate molecular diagnosis of TMPRSS2-ETS fusions. PMID- 17334352 TI - Immunoglobulin VH gene analysis in gastric MALT lymphomas. AB - The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are successfully treated with Helicobacter pylori eradication alone. However, certain subsets of these tumors are resistant to the eradication treatment. As API2-MALT1 fusion is a feature of one of these subsets, we divided gastric MALT lymphomas into three groups: eradication-responsive and API2-MALT1 fusion-negative (Group A), eradication-resistant and fusion-negative (Group B), and eradication resistant and fusion-positive (Group C). To characterize further gastric MALT lymphomas, we analyzed VH genes, which do not change in the course of tumor progression, by extensive subcloning of the monoclonal PCR products of 45 cases. VH3-23 and VH3-30 were preferentially used in Group A tumors (14/23 cases, 61%) as compared with Group B (1/10 cases, 10%, P=0.0094) and Group C (2/12 cases, 17%, P=0.017). Tumors of Groups B and C used variegated VH fragments, and no dominant VH fragments were noted. Somatic mutation was detected in most of the cases. Ongoing mutation was detected in 3/45 cases (7%), when assessed according to strict criteria for a confirmed mutation. These findings suggest that inflammation-dependent tumors (Group A) may be derived from a highly restricted, probably H. pylori-associated, B cell subset and may not often progress to those that are inflammation-independent (Groups B and C). Although considered to be common in this tumor, ongoing mutation may be infrequent when assessed by strict criteria. PMID- 17334353 TI - Phyllodes tumors of the breast segregate in two groups according to genetic criteria. AB - Phyllodes tumors are rare fibroepithelial tumors of the breast. The pathologic grading of phyllodes tumors based on the aspect of the stromal component, is divided into 2 or 3 grades according to the system used. To determine whether genetic markers could be of use for improving the classification of phyllodes tumors and to provide a better knowledge of the genetic alterations in these tumors, we analyzed chromosomal changes detected by comparative genomic hybridization (CGH) in comparison with histological data, in a series of 30 cases. Recurrent chromosome imbalances were observed in 55, 91 and 100% of benign, borderline and malignant phyllodes tumors, respectively. The mean number of chromosome changes was one in benign, six in borderline, and six in malignant phyllodes tumors. Most frequent genetic imbalances were +1q (12/30), -13q (7/30), -6q (9/30), +5 (9/30) and -10p (8/30). Gains of 1q, present in only one of nine benign tumors, were found in 11/21 (51%) borderline or malignant tumors. Losses of 13q have 13q14.2 as smallest region of overlap, suggesting that the RB1 gene could be the target of deletions. Amplifications of 12q14, involving the MDM2 locus, and of 8p24, involving the MYC gene, were observed in one case each. Borderline and malignant phyllodes tumors could not be differentiated on the basis of their genomic imbalances (presence and number of chromosomal changes, presence of 1q gain and/or 13q loss). Conversely, benign tumors could be significantly differentiated from the group composed of borderline and malignant tumors (P<0.01). This study reveals two distinct patterns of genomic imbalance in phyllodes tumors: benign, with none or a few chromosome changes and malignant, with numerous recurrent chromosomal changes, in particular 1q gain and 13q loss. Helpful additional pathological criteria for differentiating the two genetic groups of phyllodes tumors are the nuclear size and the mitotic rate. PMID- 17334354 TI - Detection of tyrosinase mRNA in the sentinel lymph nodes of melanoma patients is not a predictor of short-term disease recurrence. AB - Sentinel lymph node evaluation has enabled identification of patients with cutaneous melanoma who might benefit from elective regional lymph node dissection. Sentinel nodes are currently assessed by histologic and reverse transcription polymerase chain reaction (RT-PCR) evaluation for melanocyte specific markers. The clinical significance of positive findings by RT-PCR in the absence of histologic evidence of metastasis (HIS(NEG)/PCR(POS)) remains unclear. Examination of 264 lymph nodes from 139 patients revealed histopathologic positivity in 34 patients (24.5%), in which 26 also demonstrated simultaneous RT PCR positivity (HIS(POS)/PCR(POS)). Of 35 HIS(NEG)/PCR(POS) patients (25.2%), five also had nodal capsular nevi. In total, capsular nevi were detected in 13 patients (9.4%). A total of 70 patients (50.4%) had negative sentinel nodes by both histopathology and RT-PCR (HIS(NEG)/PCR(NEG)). Over a median follow-up of 25 months, local and/or systemic recurrence developed in 31 patients (22.3%). Recurrence rates were similar among patients with histopathologic evidence of sentinel lymph node metastasis, irrespective of RT-PCR status (HIS(POS)/PCR(POS) 62%; HIS(POS)/PCR(NEG) 75%). In contrast, only 10% of HIS(NEG)/PCR(NEG) patients developed recurrence, significantly less than those in either HIS(POS) group (P<0.0001). Recurrence in the HIS(NEG)/PCR(POS)/CN(NEG) group (7.7%) was comparable to that in HIS(NEG)/PCR(NEG) patients and significantly lower than that in either HIS(POS) group (P<0.0001). The only independent prognostic factors identified by multivariate analysis were the Breslow thickness of the primary tumour and histopathologic positivity of sentinel nodes. Our findings support previous observations that histopathologic evidence of metastatic melanoma in sentinel lymph nodes is an independent predictor of disease recurrence. In contrast, detection of tyrosinase mRNA by RT-PCR alone does not appear to increase the likelihood of short-term disease recurrence. PMID- 17334356 TI - Autocatalytic cleavage of Clostridium difficile toxin B. AB - Clostridium difficile, the causative agent of nosocomial antibiotic-associated diarrhoea and pseudomembranous colitis, possesses two main virulence factors: the large clostridial cytotoxins A and B. It has been proposed that toxin B is cleaved by a cytosolic factor of the eukaryotic target cell during its cellular uptake. Here we report that cleavage of not only toxin B, but also all other large clostridial cytotoxins, is an autocatalytic process dependent on host cytosolic inositolphosphate cofactors. A covalent inhibitor of aspartate proteases, 1,2-epoxy-3-(p-nitrophenoxy)propane, completely blocked toxin B function on cultured cells and was used to identify its catalytically active protease site. To our knowledge this is the first report on a bacterial toxin that uses eukaryotic signals for induced autoproteolysis to deliver its toxic domain into the cytosol of target cells. On the basis of our data, we present an integrated model for the uptake and inositolphosphate-induced activation of toxin B. PMID- 17334357 TI - p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. AB - Cardiac hypertrophy occurs as an adaptive response to increased workload to maintain cardiac function. However, prolonged cardiac hypertrophy causes heart failure, and its mechanisms are largely unknown. Here we show that cardiac angiogenesis is crucially involved in the adaptive mechanism of cardiac hypertrophy and that p53 accumulation is essential for the transition from cardiac hypertrophy to heart failure. Pressure overload initially promoted vascular growth in the heart by hypoxia-inducible factor-1 (Hif-1)-dependent induction of angiogenic factors, and inhibition of angiogenesis prevented the development of cardiac hypertrophy and induced systolic dysfunction. Sustained pressure overload induced an accumulation of p53 that inhibited Hif-1 activity and thereby impaired cardiac angiogenesis and systolic function. Conversely, promoting cardiac angiogenesis by introducing angiogenic factors or by inhibiting p53 accumulation developed hypertrophy further and restored cardiac dysfunction under chronic pressure overload. These results indicate that the anti-angiogenic property of p53 may have a crucial function in the transition from cardiac hypertrophy to heart failure. PMID- 17334358 TI - Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung. AB - How effectively and quickly endothelial caveolae can transcytose in vivo is unknown, yet critical for understanding their function and potential clinical utility. Here we use quantitative proteomics to identify aminopeptidase P (APP) concentrated in caveolae of lung endothelium. Electron microscopy confirms this and shows that APP antibody targets nanoparticles to caveolae. Dynamic intravital fluorescence microscopy reveals that targeted caveolae operate effectively as pumps, moving antibody within seconds from blood across endothelium into lung tissue, even against a concentration gradient. This active transcytosis requires normal caveolin-1 expression. Whole body gamma-scintigraphic imaging shows rapid, specific delivery into lung well beyond that achieved by standard vascular targeting. This caveolar trafficking in vivo may underscore a key physiological mechanism for selective transvascular exchange and may provide an enhanced delivery system for imaging agents, drugs, gene-therapy vectors and nanomedicines. 'In vivo proteomic imaging' as described here integrates organellar proteomics with multiple imaging techniques to identify an accessible target space that includes the transvascular pumping space of the caveola. PMID- 17334359 TI - Genome sequence of the lignocellulose-bioconverting and xylose-fermenting yeast Pichia stipitis. AB - Xylose is a major constituent of plant lignocellulose, and its fermentation is important for the bioconversion of plant biomass to fuels and chemicals. Pichia stipitis is a well-studied, native xylose-fermenting yeast. The mechanism and regulation of xylose metabolism in P. stipitis have been characterized and genes from P. stipitis have been used to engineer xylose metabolism in Saccharomyces cerevisiae. We have sequenced and assembled the complete genome of P. stipitis. The sequence data have revealed unusual aspects of genome organization, numerous genes for bioconversion, a preliminary insight into regulation of central metabolic pathways and several examples of colocalized genes with related functions. The genome sequence provides insight into how P. stipitis regulates its redox balance while very efficiently fermenting xylose under microaerobic conditions. PMID- 17334360 TI - Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons. AB - Neuronal development, plasticity and survival require activity-dependent synapse to-nucleus signaling. Most studies implicate an activity-dependent regulation of gene expression in this phenomenon. However, little is known about other nuclear functions that are regulated by synaptic activity. Here we show that a newly identified component of rat postsynaptic densities (PSDs), AIDA-1d, can regulate global protein synthesis by altering nucleolar numbers. AIDA-1d binds to the first two postsynaptic density-95/Discs large/zona occludens-1 (PDZ) domains of the scaffolding protein PSD-95 via its C-terminal three amino acids. Stimulation of NMDA receptors (NMDARs), which are also bound to PSD-95, results in a Ca2+ independent translocation of AIDA-1d to the nucleus, where it couples to Cajal bodies and induces Cajal body-nucleolar association. Long-term neuronal stimulation results in an AIDA-1-dependent increase in nucleolar numbers and protein synthesis. We propose that AIDA-1d mediates a link between synaptic activity and control of protein biosynthetic capacity by regulating nucleolar assembly. PMID- 17334361 TI - Controlling for interstimulus perceptual variance abolishes N170 face selectivity. AB - Establishing when and how the human brain differentiates between object categories is key to understanding visual cognition. Event-related potential (ERP) investigations have led to the consensus that faces selectively elicit a negative wave peaking 170 ms after presentation, the 'N170'. In such experiments, however, faces are nearly always presented from a full front view, whereas other stimuli are more perceptually variable, leading to uncontrolled interstimulus perceptual variance (ISPV). Here, we compared ERPs elicited by faces, cars and butterflies while--for the first time--controlling ISPV (low or high). Surprisingly, the N170 was sensitive, not to object category, but to ISPV. In addition, we found category effects independent of ISPV 70 ms earlier than has been generally reported. These results demonstrate early ERP category effects in the visual domain, call into question the face selectivity of the N170 and establish ISPV as a critical factor to control in experiments relying on multitrial averaging. PMID- 17334362 TI - Synaptic basis for intense thalamocortical activation of feedforward inhibitory cells in neocortex. AB - The thalamus provides fundamental input to the neocortex. This input activates inhibitory interneurons more strongly than excitatory neurons, triggering powerful feedforward inhibition. We studied the mechanisms of this selective neuronal activation using a mouse somatosensory thalamocortical preparation. Notably, the greater responsiveness of inhibitory interneurons was not caused by their distinctive intrinsic properties but was instead produced by synaptic mechanisms. Axons from the thalamus made stronger and more frequent excitatory connections onto inhibitory interneurons than onto excitatory cells. Furthermore, circuit dynamics allowed feedforward inhibition to suppress responses in excitatory cells more effectively than in interneurons. Thalamocortical excitatory currents rose quickly in interneurons, allowing them to fire action potentials before significant feedforward inhibition emerged. In contrast, thalamocortical excitatory currents rose slowly in excitatory cells, overlapping with feedforward inhibitory currents that suppress action potentials. These results demonstrate the importance of selective synaptic targeting and precise timing in the initial stages of neocortical processing. PMID- 17334363 TI - A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. AB - Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex. PMID- 17334364 TI - Genetic basis of individual differences in the response to small-molecule drugs in yeast. AB - Individual response to small-molecule drugs is variable; a drug that provides a cure for some may confer no therapeutic benefit or trigger an adverse reaction in others. To begin to understand such differences systematically, we treated 104 genotyped segregants from a cross between two yeast strains with a collection of 100 diverse small molecules. We used linkage analysis to identify 124 distinct linkages between genetic markers and response to 83 compounds. The linked markers clustered at eight genomic locations, or quantitative-trait locus 'hotspots', that contain one or more polymorphisms that affect response to multiple small molecules. We also experimentally verified that a deficiency in leucine biosynthesis caused by a deletion of LEU2 underlies sensitivity to niguldipine, which is structurally related to therapeutic calcium channel blockers, and that a natural coding-region polymorphism in the inorganic phosphate transporter PHO84 underlies sensitivity to two polychlorinated phenols that uncouple oxidative phosphorylation. Our results provide a step toward a systematic understanding of small-molecule drug action in genetically distinct individuals. PMID- 17334365 TI - Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. AB - To gain insight into the function of DNA methylation at cis-regulatory regions and its impact on gene expression, we measured methylation, RNA polymerase occupancy and histone modifications at 16,000 promoters in primary human somatic and germline cells. We find CpG-poor promoters hypermethylated in somatic cells, which does not preclude their activity. This methylation is present in male gametes and results in evolutionary loss of CpG dinucleotides, as measured by divergence between humans and primates. In contrast, strong CpG island promoters are mostly unmethylated, even when inactive. Weak CpG island promoters are distinct, as they are preferential targets for de novo methylation in somatic cells. Notably, most germline-specific genes are methylated in somatic cells, suggesting additional functional selection. These results show that promoter sequence and gene function are major predictors of promoter methylation states. Moreover, we observe that inactive unmethylated CpG island promoters show elevated levels of dimethylation of Lys4 of histone H3, suggesting that this chromatin mark may protect DNA from methylation. PMID- 17334366 TI - Mitochondrial point mutations do not limit the natural lifespan of mice. AB - Whether mitochondrial mutations cause mammalian aging, or are merely correlated with it, is an area of intense debate. Here, we use a new, highly sensitive assay to redefine the relationship between mitochondrial mutations and age. We measured the in vivo rate of change of the mitochondrial genome at a single-base pair level in mice, and we demonstrate that the mutation frequency in mouse mitochondria is more than ten times lower than previously reported. Although we observed an 11-fold increase in mitochondrial point mutations with age, we report that a mitochondrial mutator mouse was able to sustain a 500-fold higher mutation burden than normal mice, without any obvious features of rapidly accelerated aging. Thus, our results strongly indicate that mitochondrial mutations do not limit the lifespan of wild-type mice. PMID- 17334367 TI - Reversible contraction by looping of the Tcra and Tcrb loci in rearranging thymocytes. AB - Reversible contraction of immunoglobulin loci juxtaposes the variable (V) genes next to the (diversity)-joining-constant ((D)JC) gene domain, thus facilitating V (D)J recombination. Here we show that the T cell receptor beta (Tcrb) and T cell receptor alphadelta (Tcra-Tcrd) loci also underwent long-range interactions by looping in double-negative and double-positive thymocytes, respectively. Contraction of the Tcrb and Tcra loci occurred in rearranging thymocytes and was reversed at the next developmental stage. Decontraction of the Tcrb locus probably prevented further V(beta)-DJ(beta) rearrangements in double-positive thymocytes by separating the V(beta) genes from the DJC(beta) domain. In most double-negative cells, one Tcrb allele was recruited to pericentromeric heterochromatin. Such allelic positioning may facilitate asynchronous V(beta) DJ(beta) recombination. Hence, pericentromeric recruitment and locus 'decontraction' seem to contribute to the initiation and maintenance of allelic exclusion at the Tcrb locus. PMID- 17334368 TI - Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor. AB - Structural studies of complexes of T cell receptor (TCR) and peptide-major histocompatibility complex (MHC) have focused on TCRs specific for foreign antigens or native self. An unexplored category of TCRs includes those specific for self determinants bearing alterations resulting from disease, notably cancer. We determined here the structure of a human melanoma-specific TCR (E8) bound to the MHC molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase. The structure had features intermediate between 'anti-foreign' and autoimmune TCR peptide-MHC class II complexes that may reflect the hybrid nature of altered self. E8 manifested very low affinity for mutant triosephosphate isomerase-HLA DR1 despite the highly tumor-reactive properties of E8 cells. A second TCR (G4) had even lower affinity but underwent peptide-specific formation of dimers, suggesting this as a mechanism for enhancing low-affinity TCR-peptide-MHC interactions for T cell activation. PMID- 17334369 TI - Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment. AB - Lymphocyte homing is mediated by specific interaction between L-selectin on lymphocytes and the carbohydrate ligand 6-sulfo sialyl Lewis X on high endothelial venules. Here we generated mice lacking both core 1 extension and core 2 branching enzymes to assess the functions of O-glycan-borne L-selectin ligands in vivo. Mutant mice maintained robust lymphocyte homing, yet they lacked O-glycan L-selectin ligands. Biochemical analyses identified a class of N-glycans bearing the 6-sulfo sialyl Lewis X L-selectin ligand in high endothelial venules. These N-glycans supported the binding of L-selectin to high endothelial venules in vitro and contributed in vivo to O-glycan-independent lymphocyte homing in wild-type and mutant mice. Our results demonstrate the critical function of N glycan-linked 6-sulfo sialyl Lewis X in L-selectin-dependent lymphocyte homing and recruitment. PMID- 17334370 TI - Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. AB - Lung cancer is the leading cause of death from cancer in the US and the world. The high mortality rate (80-85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage. Given that cigarette smoke creates a field of injury throughout the airway, we sought to determine if gene expression in histologically normal large-airway epithelial cells obtained at bronchoscopy from smokers with suspicion of lung cancer could be used as a lung cancer biomarker. Using a training set (n = 77) and gene-expression profiles from Affymetrix HG-U133A microarrays, we identified an 80-gene biomarker that distinguishes smokers with and without lung cancer. We tested the biomarker on an independent test set (n = 52), with an accuracy of 83% (80% sensitive, 84% specific), and on an additional validation set independently obtained from five medical centers (n = 35). Our biomarker had approximately 90% sensitivity for stage 1 cancer across all subjects. Combining cytopathology of lower airway cells obtained at bronchoscopy with the biomarker yielded 95% sensitivity and a 95% negative predictive value. These findings indicate that gene expression in cytologically normal large-airway epithelial cells can serve as a lung cancer biomarker, potentially owing to a cancer-specific airway-wide response to cigarette smoke. PMID- 17334371 TI - IFN-gamma mediates CD4+ T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy. AB - Protective cell-mediated immune responses in cancer are critically dependent on T helper type 1 (T(H)1) cytokines such as interferon-gamma (IFN-gamma). We have previously shown that the combination of CD40 stimulation and interleukin-2 (IL 2) leads to synergistic antitumor responses in several models of advanced metastatic disease. We now report that after this treatment and other immunotherapy regimens, the CD4+ T-cell population, in contrast to CD8+ T cells, did not significantly increase but rather exhibited a substantial level of apoptosis that was dependent on IFN-gamma. Mice immunized with tumor cells and treated with an immunotherapy regimen that was initially protective were later unable to mount effective memory responses compared with immunized mice not receiving immunotherapy. Immunotherapy given to tumor-bearing Ifngr-/- mice resulted in restoration of secondary responses. Thus, although immunotherapeutic regimens inducing strong IFN-gamma responses can lead to successful early antitumor efficacy, they may also impair the development of durable antitumor responses. PMID- 17334372 TI - ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor. AB - Motor neuron degeneration resulting from the aggregation of the androgen receptor with an expanded polyglutamine tract (AR-polyQ) has been linked to the development of spinal and bulbar muscular atrophy (SBMA or Kennedy disease). Here we report that adding 5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3 one (ASC-J9) disrupts the interaction between AR and its coregulators, and also increases cell survival by decreasing AR-polyQ nuclear aggregation and increasing AR-polyQ degradation in cultured cells. Intraperitoneal injection of ASC-J9 into AR-polyQ transgenic SBMA mice markedly improved disease symptoms, as seen by a reduction in muscular atrophy. Notably, unlike previous approaches in which surgical or chemical castration was used to reduce SBMA symptoms, ASC-J9 treatment ameliorated SBMA symptoms by decreasing AR-97Q aggregation and increasing VEGF164 expression with little change of serum testosterone. Moreover, mice treated with ASC-J9 retained normal sexual function and fertility. Collectively, our results point to a better therapeutic and preventative approach to treating SBMA, by disrupting the interaction between AR and AR coregulators. PMID- 17334373 TI - Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. AB - Human immunodeficiency virus-1 (HIV-1) is primarily transmitted sexually. Dendritic cells (DCs) in the subepithelium transmit HIV-1 to T cells through the C-type lectin DC-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN). However, the epithelial Langerhans cells (LCs) are the first DC subset to encounter HIV-1. It has generally been assumed that LCs mediate the transmission of HIV-1 to T cells through the C-type lectin Langerin, similarly to transmission by DC-SIGN on dendritic cells (DCs). Here we show that in stark contrast to DC-SIGN, Langerin prevents HIV-1 transmission by LCs. HIV-1 captured by Langerin was internalized into Birbeck granules and degraded. Langerin inhibited LC infection and this mechanism kept LCs refractory to HIV-1 transmission; inhibition of Langerin allowed LC infection and subsequent HIV-1 transmission. Notably, LCs also inhibited T-cell infection by viral clearance through Langerin. Thus Langerin is a natural barrier to HIV-1 infection, and strategies to combat infection must enhance, preserve or, at the very least, not interfere with Langerin expression and function. PMID- 17334374 TI - Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque. AB - E. coli DNA gyrase uses the energy of ATP hydrolysis to introduce essential negative supercoils into the genome, thereby working against the mechanical stresses that accumulate in supercoiled DNA. Using a magnetic-tweezers assay, we demonstrate that small changes in force and torque can switch gyrase among three distinct modes of activity. Under low mechanical stress, gyrase introduces negative supercoils by a mechanism that depends on DNA wrapping. Elevated tension or positive torque suppresses DNA wrapping, revealing a second mode of activity that resembles the activity of topoisomerase IV. This 'distal T-segment capture' mode results in active relaxation of left-handed braids and positive supercoils. A third mode is responsible for the ATP-independent relaxation of negative supercoils. We present a branched kinetic model that quantitatively accounts for all of our single-molecule results and agrees with existing biochemical data. PMID- 17334375 TI - Sequence-specific dynamics modulate recognition specificity in WW domains. AB - The current canon attributes the binding specificity of protein-recognition motifs to distinctive chemical moieties in their constituent amino acid sequences. However, we show for a WW domain that the sequence crucial for specificity is an intrinsically flexible loop that partially rigidifies upon ligand docking. A single-residue deletion in this loop simultaneously reduces loop flexibility and ligand binding affinity. These results suggest that sequences of recognition motifs may reflect natural selection of not only chemical properties but also dynamic modes that augment specificity. PMID- 17334376 TI - Discovery of a natural thiamine adenine nucleotide. AB - Several important cofactors are adenine nucleotides with a vitamin as the catalytic moiety. Here, we report the discovery of the first adenine nucleotide containing vitamin B1: adenosine thiamine triphosphate (AThTP, 1), or thiaminylated ATP. We discovered AThTP in Escherichia coli and found that it accumulates specifically in response to carbon starvation, thereby acting as a signal rather than a cofactor. We detected smaller amounts in yeast and in plant and animal tissues. PMID- 17334377 TI - Structure-guided development of affinity probes for tyrosine kinases using chemical genetics. AB - As key components in nearly every signal transduction pathway, protein kinases are attractive targets for the regulation of cellular signaling by small-molecule inhibitors. We report the structure-guided development of 6-acrylamido-4 anilinoquinazoline irreversible kinase inhibitors that potently and selectively target rationally designed kinases bearing two selectivity elements that are not found together in any wild-type kinase: an electrophile-targeted cysteine residue and a glycine gatekeeper residue. Cocrystal structures of two irreversible quinazoline inhibitors bound to either epidermal growth factor receptor (EGFR) or engineered c-Src show covalent inhibitor binding to the targeted cysteine (Cys797 in EGFR and Cys345 in engineered c-Src). To accommodate the new covalent bond, the quinazoline core adopts positions that are different from those seen in kinase structures with reversible quinazoline inhibitors. Based on these structures, we developed a fluorescent 6-acrylamido-4-anilinoquinazoline affinity probe to report the fraction of kinase necessary for cellular signaling, and we used these reagents to quantitate the relationship between EGFR stimulation by EGF and its downstream outputs-Akt, Erk1 and Erk2. PMID- 17334378 TI - Allogeneic bone marrow transplantation for Pearson's syndrome. PMID- 17334379 TI - The impact of post-thaw colony-forming units-granulocyte/macrophage on engraftment following unrelated cord blood transplantation in pediatric recipients. AB - We retrospectively reviewed the engraftment kinetics following unrelated cord blood transplantation (CBT) in association with the post-thaw colony-forming units-granulocyte/macrophage (CFU-GM) number along with the numbers of total nucleated cells (TNC), CD34(+) cells and CD3(+) cells. A total of 71 cord blood units prepared for 53 patients (double-unit CBT in 18 patients) were evaluated. Either the number of infused CFU-GM or CD34(+) cells was significantly lower in patients who failed to achieve engraftment (P=0.028 and 0.005, respectively). Post-thaw CFU-GM, TNC and CD34(+) cells correlated with the speed of neutrophil engraftment (P=0.004, 0.037 and 0.004, respectively), whereas only CFU-GM showed a significant correlation with platelet engraftment (r=-0.385, P=0.024). In double-unit transplants, the number of CFU-GM was the only significant factor predicting engraftment of the predominating unit (P=0.006). We conclude that the post-thaw CFU-GM number is a reliable predictor of rapid engraftment after CBT as well as of the predominating unit in double-unit transplants. Thus, it would be important to perform post-thaw CFU-GM assay on cryopreserved aliquots from several candidate cord blood units in advance before CBT to avoid selecting the unit that might possess a low clonogenic potential. PMID- 17334380 TI - Chimerism monitoring following allogeneic hematopoietic stem cell transplantation. AB - Information regarding the chimeric status of hematopoietic stem cell transplantation (HSCT) recipients is of great significance when comparing different conditioning and prophylactic therapies. In recent years, short tandem repeats/variable number tandem repeats (STRs/VNTRs) have emerged as the best tool for chimerism monitoring. However, the polymorphisms of STR/VNTR markers vary within and between ethnic groups. The issue is further complicated in a heterogeneous population such as occurs in the Indian subcontinent. In the present study, we attempted to devise a robust scheme to identify a set of polymorphic STRs/VNTRs most suitable for chimerism evaluation in north Indian HCST recipients. At first, we did genotyping of 11 STR and one VNTR in 1000 randomly chosen north Indian individuals to quantify different diversity parameters. Resulting data indicated that ApoB3'HVR, FES, VWA, D3S1358 and D16S310 were most polymorphic loci with the average heterozygosity being 0.756+/ 0.17. Furthermore, all markers were genotyped in 77 HLA-matched donor-recipient pairs to evaluate the informativeness in differentiating donor's and recipient's cells. A panel of seven markers (ApoB3HVR-D3S1358-HUM-THO1-VWF-1-D16S310-FES-VWA) differentiated 98.70% of donor-recipient pairs. This set of markers also successfully monitored the graft status in 14 HSCT cases during multiple time points following HSCT. The results were compared to the commercially available AmpF/STR SGM Plus multiplex PCR kit (Applied Biosystems, Foster City, CA, USA). Our findings established that the panel of seven markers we identified was more cost-effective and informative. PMID- 17334381 TI - High-dose chemotherapy and autologous peripheral blood stem cell transfusion for adult and adolescent patients with small round cell sarcomas. AB - The treatment of small-round-cell tumors (SRCT) in adult patients remains a challenge to clinicians. In the present study, we analyzed the feasibility and efficacy of high-dose chemotherapy (HDCT) followed by autologous peripheral blood stem-cell rescue as a consolidation therapy exclusively for patients with good disease control through a single regimen of induction chemotherapy and local therapy. Twenty-one patients (12 females, median age 22.0 years) were analyzed, including seven cases with rhabdomyosarcoma (RMS) and 14 cases with Ewing's family tumors (EFT). Overall, survival was 46% and failure-free survival (FFS) was 33% at 3 years. Patients with EFT had better FFS than those with RMS, with an estimated 3-year FFS of 50% (P<0.01). There was a single case of possible treatment-related death and two cases of secondary malignancies. This study cannot conclusively determine the beneficial effects of HDCT for improving treatment outcomes in adult SRCTs due to the small number of subjects. However, study findings suggest that a subgroup of patients with EFT may obtain prolonged survival benefits from this therapy. PMID- 17334382 TI - Immature platelet fraction for prediction of platelet engraftment after allogeneic stem cell transplantation. AB - Platelet regeneration represents an important and separate element in the engraftment process for allogeneic stem cell transplantation. Fully automated flow cytometry using blood cell counters now allows reliable quantification of reticulated platelets, expressed as the immature platelet fraction (IPF). We studied the kinetics of IPF in six patients grafted with allogeneic peripheral blood stem cell transplantation (PBSCT), 12 patients with bone marrow transplantation (BMT) and seven patients with cord blood transplantation (CBT). Preconditioning therapy caused an immediate and rapid fall in tri-lineage hematopoiesis. IPF rose transiently above 3% after a mean duration of 11 days post-PBSCT, 18 days post-BMT and 19 days post-CBT. This was 1, 4 and 13 days earlier than platelet engraftment, respectively. A linear correlation model showed a close association between the rise of IPF and tri-lineage engraftment after transplantation. IPF counting may thus provide an accessible measure of thrombopoietic activity, leading to early evaluation of marrow function and allowing monitoring of platelet regeneration. PMID- 17334383 TI - A survey on patient perception of reduced-intensity transplantation in adults with sickle cell disease. AB - The development of reduced-intensity conditioning (RIC) and the success of BMT for paediatric sickle cell disease (SCD) have raised the possibility of revisiting this prospect in adults as well. In a chronic debilitating disorder managed with supportive therapy, the patients' perception is critical in the advancement of any potential curative therapy. To explore this aspect, we undertook a questionnaire-based survey on 30 adults with SCD. Sixty two per cent of the patients were ready to accept a transplant-related mortality (TRM) >10%; 30% of them a TRM >30%. A risk of graft failure (GF) >10% was acceptable to 64%, with a risk >30% acceptable to 41%. Infertility was acceptable to only 50%. Chronic graft-versus-host disease (GVHD) was unacceptable to the majority (80%). Seventy six per cent% of patients had a full sibling and 60% were willing to participate in a clinical trial of RIC transplantation. This survey suggests that the majority of adults with SCD might be willing to consider a curative option such as RIC transplantation even with a high TRM or GF. The major concerns relate to chronic GVHD and infertility. There is an urgent need to explore RIC transplants in SCD patients within the framework of a clinical trial, considering patient perception regarding cure and complications. PMID- 17334384 TI - CD34(+) progenitors are reproducibly recovered in thawed umbilical grafts, and positively influence haematopoietic reconstitution after transplantation. AB - Cord blood (CB) units are increasingly used for allogeneic transplantation. Cell dose, a major factor for CB selection, is evaluated before freezing by each CB bank, using various techniques. This may introduce variability and affect the prediction of cell recovery after thawing, or haematopoietic reconstitution. Forty-two children were transplanted at the same institution with unrelated CB units. All units were thawed and evaluated at the same cell therapy facility, using standard procedures. We investigated: (i) factors that affect cell loss after thawing, and (ii) the importance of CD34(+) cell doses. Prefreeze and post thaw CD34(+) cell doses were statistically correlated, thus suggesting that variability in numeration techniques used by different CB banks does not compromise the biological and clinical value of these figures. CD34(+) cell recovery appeared to be correlated with the absolute number of CD34(+) cells per frozen bag. Infused CD34(+) is the cell dose that better correlates with platelet reconstitution delay; in addition, when using a quartile comparison, haematopoietic recovery appeared to be related with prefreeze and post-thaw CD34(+) cell doses. We conclude that enumeration of CD34(+) cells in CB units is of biological significance, and may help select CB units and identify patients at risk of delayed recovery. PMID- 17334385 TI - Effectiveness of ganciclovir against human herpesvirus-6 excreted in saliva in stem cell transplant recipients. AB - The aim of this study was to evaluate the effect of ganciclovir on human herpesvirus-6 (HHV)-6. Forty allogeneic stem cell transplant recipients were prospectively studied by repeated sampling of the saliva. The saliva samples were assayed for HHV-6 by quantitative polymerase chain reaction. HHV-6 was detected in 33 patients. Ganciclovir was given as preemptive therapy for cytomegalovirus infection during 15 episodes that were compared to 18 episodes without any concomitant antiviral therapy. The mean HHV-6 load decreased 0.49 (s.e. 0.31) log(10)/week in patients receiving ganciclovir whereas it increased 0.15 (s.e. 0.17) log(10)/week in episodes without antiviral therapy (P=0.04). We conclude that ganciclovir can decrease the HHV-6 viral load in saliva. PMID- 17334386 TI - Gonadal shielding to irradiation is effective in protecting testicular growth and function in long-term survivors of bone marrow transplantation during childhood or adolescence. AB - An increasing number of long-term surviving bone marrow transplantation (BMT) recipients have recovered from their primary disease but are at risk of developing failure of endocrine organs. We investigated 30 recipients who underwent allogeneic BMT during childhood or adolescence. Testicular growth and function were evaluated by serial measurement of testicular volume, basal luteinizing hormone (LH), basal follicle-stimulating hormone (FSH) and testosterone levels and by gonadotropin-releasing hormone (GnRH) provocative test. Puberty started spontaneously in all patients. However, all except four patients had normal testosterone levels with elevated LH, indicating partial Leydig cell dysfunction. Standard deviation scores of testicular volume at last evaluation were statistically lower in those who had received irradiation without gonadal shield compared to those with (-2.04+/-0.45 vs -0.30+/-1.17, respectively, P<0.005), suggesting damage of testicular germinal epithelium owing to gonadal irradiation. Serial measurement of testicular volume showed a tendency of growth to stop at 10 ml in those without gonadal shield. Among the 30 patients, only one patient has fathered a child after reaching spontaneous puberty. These results suggest that gonadal shield is effective to protect testicular growth and function, although the attainment of fertility is difficult to achieve. PMID- 17334387 TI - Adaptations to energy stress dictate the ecology and evolution of the Archaea. AB - The three domains of life on Earth include the two prokaryotic groups, Archaea and Bacteria. The Archaea are distinguished from Bacteriabased on phylogenetic and biochemical differences, but currently there is no unifying ecological principle to differentiate these groups. The ecology of the Archaea is reviewed here in terms of cellular bioenergetics. Adaptation to chronic energy stress is hypothesized to be the crucial factor that distinguishes the Archaea from Bacteria. The biochemical mechanisms that enable archaea to cope with chronic energy stress include low-permeability membranes and specific catabolic pathways. Based on the ecological unity and biochemical adaptations among archaea, I propose the hypothesis that chronic energy stress is the primary selective pressure governing the evolution of the Archaea. PMID- 17334388 TI - Deregulated expression of a novel component of TFTC/STAGA histone acetyltransferase complexes, rat SGF29, in hepatocellular carcinoma: possible implication for the oncogenic potential of c-Myc. AB - c-Myc N-terminal conserved domains, MbI and MbII, are essential for c-Myc mediated transformation and transactivation. These domains recruit the STAGA (SPT3-TAF9-GCN5-acetyltransferase) coactivator complex, but not TFTC (TATA binding protein-free TAF-containing) to the target gene promoter. Although components of this complex are well conserved between yeast and mammals, four mammalian orthologs of yeast SPT8, SPT20, SGF11 and SGF29 remain to be identified. Here, we isolated a rat ortholog of yeast SGF29, a component of yeast SAGA (SPT-ADA-GCN5-acetyltransferase) complex. Both rat (r) SGF29 and c-myc mRNAs were overexpressed in five out of the eight tested rodent tumor cells. rSGF29 directly interacted with rADA3 and co-immunoprecipitated with two other TFTC/STAGA components, rGCN5 and rSPT3. rSGF29 was recruited to the c-Myc target gene promoters together with c-Myc, and it activated c-Myc target gene expressions. Downregulation of rSGF29 suppressed the expression of c-Myc target genes and inhibited anchorage-independent growth and tumorigenicity and lung metastasis of rat hepatoma K2 cells when injected into nude mice. These results show that rSGF29 is a novel component of TFTC/STAGA complexes and could be involved in the c-Myc-mediated malignant transformation. PMID- 17334389 TI - Opposing roles of netrin-1 and the dependence receptor DCC in cancer cell invasion, tumor growth and metastasis. AB - Deleted in colon cancer (DCC) and UNC5 function as netrin dependence receptors by inducing apoptosis in the absence of their ligand and accordingly were recently designated as putative conditional tumor suppressors. Herein, we determined whether netrin-1 and its receptors are implicated in cancer cell invasion and tumor progression. Expression of DCC, UNC5 and adenosine A2B-receptors (A2B-Rs) was investigated by reverse transcription polymerase chain reaction in human colon cancer cells. The impact of DCC restitution and netrin-1 was evaluated on collagen type I invasion, tumor growth and metastasis in nude mice, cancer cell survival and gene expression profiling. Flow cytometry, poly(ADP ribose)polymerase-1 and caspase-8 activation were used to evaluate the impact of DCC on cell death. Both netrin-1 and A2B-R activation induced the invasive phenotype through the Rho-Rho kinase axis in DCC-deficient human colorectal cancer cells. Restitution of wild-type DCC blocked invasion induced by netrin-1, A2B-R agonist and other agents. Ectopic expression of netrin-1 led to increased growth of human colon tumor xenografts in athymic mice. Conversely, introduction of wt-DCC in kidney MDCKts.src-ggl cells strongly inhibited metastasis in lymph nodes and lungs and increased sensitivity to apoptosis in hypoxia. DNA microarrays revealed that netrin and DCC had common and divergent impacts on gene expression linked to cell cycle, survival, surface signaling and adhesion. Our findings underscore that netrin is a potent invasion and tumor growth-promoting agent and that DCC is a metastasis suppressor gene targeting both proinvasive and survival pathways in a cumulative manner. PMID- 17334390 TI - Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition. AB - Rapamycin, a natural product inhibitor of the Raptor-mammalian target of rapamycin complex (mTORC1), is known to induce Protein kinase B (Akt/PKB) Ser-473 phosphorylation in a subset of human cancer cell lines through inactivation of S6K1, stabilization of insulin receptor substrate (IRS)-1, and increased signaling through the insulin/insulin-like growth factor-I/phosphatidylinositol 3 kinase (PI3K) axis. We report that A-443654, a potent small-molecule inhibitor of Akt serine/threonine kinases, induces Akt Ser-473 phosphorylation in all human cancer cell lines tested, including PTEN- and TSC2-deficient lines. This phenomenon is dose-dependent, manifests coincident with Akt inhibition and likely represents an alternative, rapid-feedback pathway that can be functionally dissociated from mTORC1 inhibition. Experiments performed in TSC2-/- cells indicate that TSC2 and IRS-1 cooperate with, but are dispensable for, A-443654 mediated Akt phosphorylation. This feedback event does require PI3K activity, however, as it can be inhibited by LY294002 or wortmannin. Small interfering RNA mediated knockdown of mTOR or Rictor, components of the rapamycin-insensitive mTORC2 complex, but not the mTORC1 component Raptor, also inhibited Akt Ser-473 phosphorylation induced by A-443654. Our data thus indicate that Akt phosphorylation and activity are coupled in a manner not previously appreciated and provide a novel mode of Akt regulation that is distinct from the previously described rapamycin-induced IRS-1 stabilization mechanism. PMID- 17334391 TI - A dual role for the API2 moiety in API2-MALT1-dependent NF-kappaB activation: heterotypic oligomerization and TRAF2 recruitment. AB - Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid neoplasm. Chromosomal translocation t(11;18)(q21,q21) is found in 30% of gastric MALT lymphomas and is associated with a failure to respond to standard treatment and a tendency to disseminate. This translocation generates a chimeric protein composed of N-terminal sequences of Inhibitor of Apoptosis 2 (API2, also known as BIRC3 and cIAP2) fused to C-terminal sequences of MALT1. API2-MALT1 promotes cell survival and proliferation via activation of nuclear factor-kappaB (NF-kappaB). Here, we investigate the mechanism by which the API2 moiety contributes to NF-kappaB stimulation. We find that the API2 moiety mediates oligomerization of API2-MALT1 as well as interaction with tumor necrosis factor receptor-associated factor 2 (TRAF2). Surprisingly, oligomerization does not occur via homotypic interaction; rather, the API2 moiety of one monomer interacts with the MALT1 moiety of another monomer. Further, the specific region of the API2 moiety responsible for mediating oligomerization is distinct from that mediating TRAF2 binding. Although deletion or mutation of the TRAF2 binding site does not inhibit oligomerization, it does lead to dramatically decreased NF kappaB activation. Deletion of both TRAF2 binding and oligomerization regions results in near-complete loss of NF-kappaB activation. Thus, API2 moiety-mediated heterotypic oligomerization and TRAF2 binding both contribute to maximal API2 MALT1-dependent NF-kappaB stimulation. PMID- 17334392 TI - A crucial role of plasma membrane-associated sialidase in the survival of human cancer cells. AB - Human plasma membrane-associated sialidase (NEU3), a key enzyme for ganglioside degradation, is markedly upregulated in human cancers, leading to apoptosis suppression. To define molecular mechanisms and the possible target for NEU3, its encoding gene was silenced by small interference RNA (siRNA) or overexpressed in human cells. NEU3 siRNA-induced apoptosis with no special stimuli in HeLa cells, accompanied with decreased Bcl-xL and increased mda7 and GM3 synthase mRNA levels, whereas overexpression resulted in the opposite. Carcinoma HT-29 and MCF 7 cells appeared to be similarly affected, but normal cell lines demonstrated no significant changes. NEU3 siRNA was found to inhibit and NEU3 overexpression to stimulate Ras activation with consequent influence on extracellular signal regulated kinases and Akt. Ras activation by NEU3 was abrogated by PP2 (src inhibitor) or AG1478 (epidermal growth factor receptor (EGFR) inhibitor), and NEU3 actually enhanced EGF-stimulated tyrosine-phosphorylation of EGFR, suggesting that the upstream targets might be tyrosine kinases including src and EGFR, and the subsequent stimulation of Ras cascade leads to the inhibition of cell apoptosis. Glycolipid changes observed seemed to be one of the causes of the cell effects. NEU3 may thus be an essential gene for cancer cell survival and siRNAs targeting this protein could have utility for gene-based therapy of human cancers. PMID- 17334393 TI - Estrogen receptor-positive mammary tumorigenesis in TGFalpha transgenic mice progresses with progesterone receptor loss. AB - We characterized the novel NRL-transforming growth factor alpha (NRL-TGFalpha) transgenic mouse model in which growth factor - steroid receptor interactions were explored. The NRL promoter directs transgene expression to mammary ductal and alveolar cells and is nonresponsive to estrogen manipulations in vitro and in vivo. NRL-TGFalpha mice acquire proliferative hyperplasias as well as cystic and solid tumors. Quantitative transcript analysis revealed a progressive decrease in estrogen receptor alpha (ER) and progesterone receptor (PR) mRNA levels with tumorigenesis. However, ER protein was evident in all lesion types and in surrounding stromal cells using immunohistochemistry. PR protein was identified in normal epithelial cells and in very few cells of small epithelial hyperplasias, but never in stromal or tumor cells. Prophylactic ovariectomy significantly delayed tumor development and decreased incidence. Finally, while heterozygous (+/-) p53 mice did not acquire mammary lesions, p53+/- mice carrying the NRL-TGFalpha transgene developed ER negative/PR negative undifferentiated carcinomas. These data demonstrate that unregulated TGFalpha expression in the mammary gland leads to oncogenesis that is dependent on ovarian steroids early in tumorigenesis. Resulting tumors resemble a clinical phenotype of ER+/PR-, and when combined with a heterozygous p53 genotype, ER-/PR-. PMID- 17334394 TI - SGNE1/7B2 is epigenetically altered and transcriptionally downregulated in human medulloblastomas. AB - In a genome-wide screen using differential methylation hybridization (DMH), we have identified a CpG island within the 5' region and untranslated first exon of the secretory granule neuroendocrine protein 1 gene (SGNE1/7B2) that showed hypermethylation in medulloblastomas compared to fetal cerebellum. Bisulfite sequencing and combined bisulfite restriction assay were performed to confirm the methylation status of this CpG island in primary medulloblastomas and medulloblastoma cell lines. Hypermethylation was detected in 16/23 (70%) biopsies and 7/8 (87%) medulloblastoma cell lines, but not in non-neoplastic fetal (n=8) cerebellum. Expression of SGNE1 was investigated by semi-quantitative competitive reverse transcription-polymerase chain reaction and found to be significantly downregulated or absent in all, but one primary medulloblastomas and all cell lines compared to fetal cerebellum. After treatment of medulloblastoma cell lines with 5-aza-2'-deoxycytidine, transcription of SGNE1 was restored. No mutation was found in the coding region of SGNE1 by single-strand conformation polymorphism analysis. Reintroduction of SGNE1 into the medulloblastoma cell line D283Med led to a significant growth suppression and reduced colony formation. In summary, we have identified SGNE1 as a novel epigenetically silenced gene in medulloblastomas. Its frequent inactivation, as well as its inhibitory effect on tumor cell proliferation and focus formation strongly argues for a significant role in medulloblastoma development. PMID- 17334395 TI - p63 and p73 in human cancer: defining the network. AB - The p53-related genes p63 and p73 exhibit significant structural homology to p53; however, they do not function as classical tumor suppressors and are rarely mutated in human cancers. Both p63 and p73 exhibit tissue-specific roles in normal development and a complex contribution to tumorigenesis that is due to their expression as multiple protein isoforms. The predominant p63/p73 isoforms expressed both in normal development and in many tumors lack the conserved transactivation (TA) domain; these isoforms instead exhibit a truncated N terminus (DeltaN) and function at least in part as transcriptional repressors. p63 and p73 isoforms are regulated through both transcriptional and post translational mechanisms, and they in turn regulate diverse cellular functions including proliferation, survival and differentiation. The net effect of p63/p73 expression in a given context depends on the ratio of TA/DeltaN isoforms expressed, on physical interaction between p63 and p73 isoforms, and on functional interactions with p53 at the promoters of specific downstream target genes. These multifaceted interactions occur in diverse ways in tumor-specific contexts, demonstrating a functional 'p53 family network' in human tumorigenesis. Understanding the regulation and mechanistic contributions of p63 and p73 in human cancers may ultimately provide new therapeutic opportunities for a variety of these diseases. PMID- 17334396 TI - p120-catenin is required for the collective invasion of squamous cell carcinoma cells via a phosphorylation-independent mechanism. AB - Loss of E-cadherin-mediated cell-cell junctions has been correlated with cancer cell invasion and poor patient survival. p120-catenin has emerged as a key player in promoting E-cadherin stability and adherens junction integrity and has been proposed as a potential invasion suppressor by preventing release of cells from the constraints imposed by cadherin-mediated cell-cell adhesion. However, it has been proposed that tyrosine phosphorylation of p120 may contribute to cadherin dependent junction disassembly during invasion. Here, we use small interfering RNA (siRNA) in A431 cells to show that knockdown of p120 promotes two-dimensional migration of cells. In contrast, p120 knockdown impairs epidermal growth factor induced A431 invasion into three-dimensional matrix gels or in organotypic culture, whereas re-expression of siRNA-resistant p120, or a p120 isoform that cannot be phosphorylated on tyrosine, restores the collective mode of invasion employed by A431 cells in vitro. Thus, p120 promotes A431 cell invasion in a phosphorylation-independent manner. We show that the collective invasion of A431 cells depends on the presence of cadherin-mediated (P- and E-cadherin) cell-cell contacts, which are lost in cells where p120 expression is knocked down. Furthermore, membranous p120 is maintained in invasive squamous cell carcinomas in tumours suggesting that p120 may be important for the collective invasion of tumours cells in vivo. PMID- 17334397 TI - p38alpha and p38delta mitogen-activated protein kinase isoforms regulate invasion and growth of head and neck squamous carcinoma cells. AB - Recent studies indicate that the specificity of p38 mitogen-activated protein kinase (MAPK)-mediated cellular stress responses is determined by the expression pattern of the distinct p38 isoforms. Here, we have analysed the function of distinct p38 isoforms in the growth and invasion of head and neck squamous cell carcinomas (HNSCCs). Activation of p38 MAPK by arsenite resulted in inactivation of the ERK1,2 signaling pathway by dephosphorylation of MEK1,2 in primary human epidermal keratinocytes (HEKs), whereas in HNSCC cells this p38-mediated inhibition of the ERK1,2 pathway was absent. Quantitation of p38 pathway component mRNA expression in HNSCC cell lines (n=42) compared to HEKs (n=8) revealed that p38alpha and p38delta isoforms are predominantly expressed in both cell types and that MKK3 is the primary upstream activator expressed. Inhibition of endogenous p38alpha or p38delta activity by adenoviral delivery of corresponding dominant-negative p38 isoforms potently reduced MMP-13 and MMP-1 expressions, and suppressed the invasion of HNSCC cells through collagen. Dominant-negative p38alpha and p38delta inhibited squamous cell carcinoma (SCC) cell proliferation and inhibition of p38alpha activity also compromised survival of SCC cells. p38alpha and p38delta were predominantly expressed in HNSCCs (n=24) and nonneoplastic epithelium in vivo (n=6), with MKK3 being the primary upstream activator. Activation and expression of p38alpha and p38delta by tumor cells was detected in HNSCCs in vivo (n=16). Adenoviral expression of dominant-negative p38alpha or p38delta in cutaneous SCC cells potently inhibited their implantation in skin of severe combined immunodeficiency mice and growth of xenografts in vivo. Our results indicate that p38alpha and p38delta specifically promote the malignant phenotype of SCC cells by regulating cell survival, proliferation and invasion, suggesting these p38 MAPK isoforms as potential therapeutic targets in HNSCCs. PMID- 17334398 TI - Requirement of Rac1 distinguishes follicular from interfollicular epithelial stem cells. AB - Epithelial stem cells in the bulge region within the hair follicle maintain the cyclic hair growth, but whether these stem cells also contribute to the epidermal renewal remains unclear. Here, we observed that the conditional deletion of the Rac1 gene in the mouse skin, including the potential follicular and epidermal stem cell compartments, results in alopecia owing to defective hair development. Surprisingly, mice lacking the expression of this Rho GTPase do not display major alterations in the interfollicular skin. Furthermore, Rac1 excision from primary epithelial keratinocytes results in the inability to reconstitute hair follicles and sebaceous glands when grafted onto mice, but epithelial cells lacking Rac1 can nonetheless form a healthy epidermis. Together, these findings support the emerging view that the epidermis and the hair follicles are maintained by different epithelial stem cells, and provide evidence that the requirement for Rac1 function can distinguish these distinct stem cells populations. PMID- 17334399 TI - Functional consequences of cyclin D1/BRCA1 interaction in breast cancer cells. AB - The inheritance of one defective BRCA1 or BRCA2 allele predisposes an individual to developing breast and ovarian cancers. BRCA1 is a multifunctional tumor suppressor protein, which through interaction with a vast array of proteins has implications in processes such as cell cycle, transcription, DNA damage response and chromatin remodeling. Conversely, the oncogene, cyclin D1 is overexpressed in about 35% of all breast cancer cases. In this study, we provide detailed analyses on the phosphorylation state of BRCA1 by cyclin D1/cdk4 complexes. In particular, we have identified Ser 632 of BRCA1 as a cyclin D1/cdk4 phosphorylation site in vitro. Using chromatin immunoprecipitation assays, we observed that the inhibition of cyclin D1/cdk4 activity resulted in increased BRCA1 DNA binding at particular promoters in vivo. In addition, we identified multiple novel genes that are bound by BRCA1 in vivo. Collectively, these results indicate that cyclin D1/cdk4-mediated phosphorylation of BRCA1 inhibits the ability of BRCA1 to be recruited to particular promoters in vivo. Therefore, cyclin D1/Cdk4 phosphorylation of BRCA1 could provide a mechanism to interfere with the DNA dependent activities of BRCA1. PMID- 17334400 TI - TBP-1 protects the human oncosuppressor p14ARF from proteasomal degradation. AB - The p14ARF tumor suppressor is a key regulator of cellular proliferation, frequently inactivated in human cancer. The mechanisms that regulate alternative reading frame (ARF) turnover have been obscure for long time, being ARF a relatively stable protein. Recently, it has been described that its degradation depends, at least in part, on the proteasome and that it can be subjected to N terminal ubiquitination. We have previously reported that ARF protein levels are regulated by TBP-1 (Tat-Binding Protein 1), a multifunctional protein, component of the regulatory subunit of the proteasome, involved in different cellular processes. Here we demonstrate that the stabilization effect exerted by TBP-1 requires an intact N-terminal 39 amino acids in ARF and occurs independently from N-terminal ubiquitination of the protein. Furthermore, we observed that ARF can be degraded in vitro by the 20S proteasome, in the absence of ubiquitination and this effect can be counteracted by TBP-1. These observations seem relevant in the comprehension of the regulation of ARF metabolism as, among the plethora of cellular ARF's interactors already identified, only NPM/B23 and TBP-1 appear to be involved in the control of ARF intracellular levels. PMID- 17334401 TI - Repression of intestinal drug metabolizing enzymes by the SV40 large T antigen. AB - Toxic compounds such as carcinogens are removed from the body by the action of a series of detoxifying enzymes and transporters expressed in the liver and the small intestine. We have found that intestinal epithelial cells expressing the SV40 large T antigen (TAg) contain significantly lower levels of mRNAs, encoding several drug metabolizing/detoxifying enzymes and transporters compared to their non-transgenic littermates. In addition, TAg blocks the induction of these mRNAs by xenobiotics. The repression depends on an intact LXCXE motif in TAg, suggesting that inactivation of the retinoblastoma (Rb) family of tumor suppressors plays a role in the process. These results imply that a functional Rb pathway in the intestine is necessary for the expression of the detoxification system used to clear carcinogens, and suggest that loss of this tumor suppressor might alter susceptibility to chemical injury. In addition, the effect of TAg on the detoxification pathway appears to be tissue-specific, as its ectopic expression in the liver failed to suppress the P450 enzymes. The TAg-mediated suppression of drug metabolizing/detoxifying enzymes may have broad implications in the metabolism and mechanism of action of both carcinogens and prescription drugs. PMID- 17334402 TI - Seeing science in color. AB - Around 7%-10% of men have some form of what is commonly called red-green color blindness. New style specifications at Nature Structural & Molecular Biology aim to enable all readers to see the full spectrum of data in images. PMID- 17334403 TI - Splicing oncogenes. PMID- 17334404 TI - A common means to an end. PMID- 17334405 TI - 'Arc' escorts siRNAs in heterochromatin assembly. PMID- 17334406 TI - How to gate an ion channel: lessons from MthK. PMID- 17334408 TI - Quantitative analysis of estrogen receptor heterogeneity in breast cancer. AB - Immunohistochemical analyses (IHC) of biomarkers are extensively used for tumor characterization and as prognostic and predictive measures. The current standard of single slide analysis assumes that one 5 microM section is representative of the entire tumor. We used our automated image analysis technology (AQUA) using a modified IHC technique with fluorophores to compare estrogen receptor (ER) expression in multiple blocks/slides from cases of primary breast cancer with the objective of quantifying tumor heterogeneity within sections and between blocks. To normalize our ER scores and allow slide-to-slide comparisons, 0.6 microm histospots of representative breast cancer cases with known ER scores were assembled into a 'gold standard array' (GSA) and placed adjacently to each whole section. Overall, there was excellent correlation between AQUA scores and the pathologist's scores and reproducibility of GSA scores (mean linear regression R value 0.8903). Twenty-nine slides from 11 surgical cases were then analyzed totaling over 2000 AQUA images. Using standard binary assignments of AQUA (>10) and pathologist's (>10%) scores as being positive, there was fair concordancy between AQUA and pathologist scores (73%) and between slides from different blocks from the same cases (75%). However using continuous AQUA scores, agreement between AQUA and pathologist was far lower and between slides from different blocks from the same cases only 19%. Within individual slides there was also significant heterogeneity in a scattered pattern, most notably for slides with the highest AQUA scores. In sum, using a quantitative measure of ER expression, significant block-to-block heterogeneity was found in 81% of cases. These results most likely reflect both laboratory-based variability due to lack of standardization of immunohistochemistry and true biological heterogeneity. It is also likely to be dependent on the biomarker analyzed and suggests further studies should be carried out to determine how these findings may affect clinical decision-making processes. PMID- 17334409 TI - CD95 ligand-dependant endothelial cell death initiates oral mucosa damage in a murine model of acute graft versus host disease. AB - Oral mucosa lesions are one of the common pathological consequences of acute graft versus host disease (aGVHD), the major complication of allogeneic bone marrow transplantation caused by mature T lymphocytes of donor origin. Oral mucosa damage in aGVHD is characterized by apoptosis induction in the basal keratinocytes, associated with immune effector T-cell infiltration, but its pathogenesis remains unclear because these lesions might result from the patient conditioning therapy that includes radiation and/or chemotherapy. Here, using a murine model of aGVHD that does not involve any conditioning treatment, we show that the earliest detectable oral mucosa lesion is apoptosis of the endothelial cells from chorion capillaries, which precedes basal keratinocyte apoptosis induction. Neither vascular damage nor epithelial-cell death occurred in recipients of allogeneic lymphocytes from CD95 ligand (CD95L)-defective mice. Our findings indicate that oral mucosa lesions in aGVHD are initiated by endothelial cell death and require CD95L expression by the allogeneic lymphocytes. This early vascular damage may contribute to the induction of further tissue damage in the oral mucosa, through the induction of hypoxia and vascular leakage of immune cells or soluble proapoptotic mediators. PMID- 17334410 TI - FR-167653, a selective p38 MAPK inhibitor, exerts salutary effect on liver cirrhosis through downregulation of Runx2. AB - Liver cirrhosis remains a difficult-to-treat disease with a substantial morbidity and mortality rate. There is an emerging body of data purporting a pivotal role of the activated p38 mitogen-activated protein kinase (MAPK) in the process of cirrhosis. Several anticirrhotic agents have been developed over the past few years, and most of them exert their effects by indirectly inhibiting the p38 pathway. Effect of a selective p38 inhibitor is yet to be reported. In this study, we evaluated the salutary effect of FR-167653 (FR), a selective p38 inhibitor, in a carbon tetrachloride (CCl(4))-induced rat cirrhotic model. Twenty rats were assigned into four groups: Sham, olive oil only; Control, CCl(4) in olive oil; FR50, FR 50 mg/kg/day and CCl(4); and FR100, FR 100 mg/kg/day and CCl(4). FR dose-dependently inhibited activation of p38 and had an ameliorating effect on cirrhosis formation. Significant dose-dependent reduction in alpha smooth muscle actin immunostaining and hydroxyproline content of the liver was noticed in the FR-treated rats. Also densitometric analysis showed a significant reduction in azan-stained area in the FR-treated rats. These fibrotic changes were observed in the myofibroblasts including the hepatic stellate cells and portal fibroblasts. mRNA expression of runt-related protein 2 (Runx2), a profibrogenic transcription factor, was significantly low in FR-treated livers, indicating that Runx2 might be a key downstream regulator of the p38 pathway. A similar reduction in expression of Smad4 and tissue inhibitor of metalloproteinase-1 was noticed in the FR-treated rats. In conclusion, FR treatment exerted a significant beneficial effect in a CCl(4)-induced rat cirrhotic model. The ameliorating effect of FR could be partially attributable to an inhibition of the Smad4/p38/Runx2 axis in the cirrhotic liver. PMID- 17334411 TI - Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation. AB - In bile duct-ligated (BDL) rodents, as in humans with chronic cholangiopathies, biliary obstruction triggers proliferation of bile ductular cells that are surrounded by fibrosis produced by adjacent myofibroblastic cells in the hepatic mesenchyme. The proximity of the myofibroblasts and cholangiocytes suggests that mesenchymal-epithelial crosstalk promotes the fibroproliferative response to cholestatic liver injury. Studying BDL mice, we found that bile duct obstruction induces activity of the Hedgehog (Hh) pathway, a system that regulates the viability and differentiation of various progenitors during embryogenesis. After BDL, many bile ductular cells and fibroblastic-appearing cells in the portal stroma express Hh ligands, receptor and/or target genes. Transwell cocultures of an immature cholangiocyte line that expresses the Hh receptor, Patched (Ptc), with liver myofibroblastic cells demonstrated that both cell types produced Hh ligands that enhanced each other's viability and proliferation. Further support for the concept that Hh signaling modulates the response to BDL was generated by studying PtcLacZ mice, which have an impaired ability to constrain Hh signaling due to a heterozygous deficiency of Ptc. After BDL, PtcLacZ mice upregulated fibrosis gene expression earlier than wild-type controls and manifested an unusually intense ductular reaction, more expanded fibrotic portal areas, and a greater number of lobular necrotic foci. Our findings reveal that adult livers resurrect developmental signaling systems, such as the Hh pathway, to guide remodeling of the biliary epithelia and stroma after cholestatic injury. PMID- 17334412 TI - A DNA aptamer population specifically detects Leishmania infantum H2A antigen. AB - Aptamers are short single-stranded DNA or RNA oligonucleotides that are selected in vitro by their affinity and specificity for the target. Binding is a consequence of the particular tertiary structure that they are able to acquire, depending on their sequence. Parasites of the genus Leishmania belongs to the lower eukaryote order Kinetoplastida that causes leishmaniosis in man and animals. Histone genes in Leishmania are of considerable interest because these flagellates do not condense their chromatin during mitosis. Thus, the study of the structural features of histones has been considered of particular interest and, as a result, in recent years a great number of histone genes have been characterized in trypanosomatids. Histones are extremely conserved proteins, reflecting their apparent universality of function. Sequence similarity of kinetoplastid core histones those of higher eukaryotes is found predominantly in the globular region with high sequence divergences in the N- and in the C terminal domains. These divergences indicate that they may be potential diagnostic and/or therapeutics targets. We have successfully isolated a pool of DNA sequences, named SELH2A, which specifically binds to Leishmania infantum H2A. When tested in an enzyme-linked oligonucleotide assay, slot blot and Western blot analysis, the aptamer pool exhibited specificity in its ability to bind only to H2A antigen but not to other proteins from L. infantum including other histones. Thus, it appears that this novel anti-H2A aptamer population may be of potential application as a diagnostic system for leishmaniosis. PMID- 17334414 TI - Granulocyte colony-stimulating factor improves left ventricular function of doxorubicin-induced cardiomyopathy. AB - It is not well-known yet how granulocyte colony-stimulating factor (G-CSF) affects nonischemic cardiomyopathy, though its beneficial effects on acute myocardial infarction are well-established. We hypothesize that G-CSF beneficially might affect nonischemic cardiomyopathy through the direct cardioprotective effects. Here, we show that a single injection of doxorubicin (DOX, 15 mg/kg) induced left ventricular dilatation and dysfunction in mice within 2 weeks, and that these effects were significantly attenuated by human recombinant G-CSF (100 microg/kg/day for 5 days). G-CSF also protected hearts against DOX-induced cardiomyocyte atrophy/degeneration, fibrosis, inflammatory cell infiltration and down regulation of GATA-4 and sarcomeric proteins, myosin heavy chain, troponin I and desmin, both in vivo and in vitro. Cardiac cyclooxygenase-2 was upregulated and G-CSF receptor was downregulated in DOX induced cardiomyopathy, but both of those effects were largely reversed by G-CSF. No DOX-induced apoptotic effects were seen, nor were there any changes in tumor necrosis factor-alpha or transforming growth factor-beta1 levels. Among downstream mediators of G-CSF receptor signaling, DOX-induced cardiomyopathy involved inactivation of extracellular signal-regulated protein kinase (ERK); the ERK inactivation was reversed by G-CSF. Inhibition of ERK activation, but not cyclooxygenase-2 inhibition, completely abolished beneficial effect of G-CSF on cardiac function. G-CSF did not promote differentiation of bone marrow cells into cardiomyocytes according to the experiment using green fluorescent protein chimeric mice, and inhibition of CXCR4+ cell homing using AMD3100 did not diminish the effect of G-CSF. Finally, G-CSF was also effective when administered after cardiomyopathy was established. In conclusion, these findings imply the therapeutic usefulness of G-CSF mainly through restoring ERK activation against DOX-induced nonischemic cardiomyopathy. PMID- 17334415 TI - Herbal medicine during pregnancy & lactation. PMID- 17334413 TI - H3 histamine receptor agonist inhibits biliary growth of BDL rats by downregulation of the cAMP-dependent PKA/ERK1/2/ELK-1 pathway. AB - Histamine regulates many functions by binding to four histamine G-coupled receptor proteins (H1R, H2R, H3R and H4R). As H3R exerts their effects by coupling to Galpha(i/o) proteins reducing adenosine 3', 5'-monophosphate (cAMP) levels (a key player in the modulation of cholangiocyte hyperplasia/damage), we evaluated the role of H3R in the regulation of biliary growth. We posed the following questions: (1) Do cholangiocytes express H3R? (2) Does in vivo administration of (R)-(alpha)-(-)-methylhistamine dihydrobromide (RAMH) (H3R agonist), thioperamide maleate (H3R antagonist) or histamine, in the absence/presence of thioperamide maleate, to bile duct ligated (BDL) rats regulate cholangiocyte proliferation? and (3) Does RAMH inhibit cholangiocyte proliferation by downregulation of cAMP-dependent phosphorylation of protein kinase A (PKA)/extracellular signal-regulated kinase 1/2 (ERK1/2)/ets-like gene-1 (Elk-1)? The expression of H3R was evaluated in liver sections by immunohistochemistry and immunofluorescence, and by real-time PCR in cholangiocyte RNA from normal and BDL rats. BDL rats (immediately after BDL) were treated daily with RAMH, thioperamide maleate or histamine in the absence/presence of thioperamide maleate for 1 week. Following in vivo treatment of BDL rats with RAMH for 1 week, and in vitro stimulation of BDL cholangiocytes with RAMH, we evaluated cholangiocyte proliferation, cAMP levels and PKA, ERK1/2 and Elk-1 phosphorylation. Cholangiocytes from normal and BDL rats express H3R. The expression of H3R mRNA increased in BDL compared to normal cholangiocytes. Histamine decreased cholangiocyte growth of BDL rats to a lower extent than that observed in BDL RAMH-treated rats; histamine-induced inhibition of cholangiocyte growth was partly blocked by thioperamide maleate. In BDL rats treated with thioperamide maleate, cholangiocyte hyperplasia was slightly higher than that of BDL rats. In vitro, RAMH inhibited the proliferation of BDL cholangiocytes. RAMH inhibition of cholangiocyte growth was associated with decreased cAMP levels and PKA/ERK1/2/Elk-1 phosphorylation. Downregulation of cAMP-dependent PKA/ERK1/2/Elk 1 phosphorylation (by activation of H3R) is important in the inhibition of cholangiocyte growth in liver diseases. PMID- 17334416 TI - Histopathological analysis of hysterectomy specimens. AB - This was a retrospective study carried out on all hysterectomy specimens sent to Department of Pathology of Tribhuvan University Teaching Hospital, Kathmandu, Nepal from 1st September 2005 to 28th February 2006, to study the histopathological findings of these specimens. All informations used in the study were obtained from the records of Department of Pathology of the hospital. Out of 221 hysterectomy specimens received during the study period, 139 (62.9%) were total abdominal and 82 (37.1%) were vaginal hysterectomy specimens. Mean age of the patient was 53.4 years for vaginal hysterectomy group where as it was 37.6 years for total abdominal hysterectomy with unilateral salpingo-oophorectomy and 46.3 years for total abdominal hysterectomy with bilateral salpingo-oophorectomy group. Uterine prolapse was commonest indication of hysterectomy overall (37.1%) and accounted for 98.8% of vaginal hysterectomies. Other common indications of hysterectomy were uterine fibroid (24.9%), ovarian tumor (14.9%) and dysfunctional uterine bleeding (7.7%). Leimyoma was the most common pathology found in uterine corpus (27.1%). Chronic cervicitis in cervix, functional cysts in ovaries and paratubal cysts in fallopian tubes were most common histological findings. Ovarian neoplasms accounted for 18.3% of ovarian pathology. 38% specimens were unremarkable histopathologically. In Tribhuvan University Teaching Hospital, abdominal hysterectomies are more common than vaginal hysterectomies. Most vaginal hysterectomies are done for uterine prolapse and patients are older than those undergoing abdominal hysterectomies. Most abdominal hysterectomies are performed for uterine leiomyomas. Hysterectomy specimens may be unremarkable histopathologically, most of which are vaginal hysterectomies done for uterine prolapse. PMID- 17334417 TI - Serum urea, creatinine and electrolyte status in patients presenting with acute gastroenteritis. AB - The present study was undertaken to estimate the serum urea, creatinine and electrolyte status of patients presenting with acute gastroenteritis. Sixty patients who presented to Kathmandu Medical College and Teaching hospital from 15 June to 15 July 2005 with acute diarrhea with or without associated vomiting, causing dehydration severe enough to require hospital admission were investigated for serum urea, creatinine and electrolyte level. Out of 60 patients investigated, serum sodium and potassium level were available for 34 patients. Only one (2.9%) patients had sodium level below 135mEq/l, thirty two (94.11%) had sodium level between 135-146 mEq/l and one (2.9%) had sodium level above 146mEq/l. Similarly 9 (26.47%) patients had potassium level below 3.5mEq/l, 22 (64.70%) patients had potassium level between 3.5-5 mEq/l and 3 (8.82%) patients had level above 5 mEq/l. Serum urea and creatinine level were available for 47 patients. 36 (76.59%) patients had serum urea level between 15-45mg/dl and 11 (23.40%) patients had urea level above 45 mg/dl. 35 (74.46%) patients had serum creatinine level between 0.5-1.4 mg/dl and 12 (25.53%) had serum creatinine level above 1.4 mg/dl. In this study hypokalaemia was noticed more than hyponatremia and significant number of patients also showed increased level of serum urea and creatinine. Therefore, serum urea, creatinine and electrolytes should be closely monitored in patients with acute gastroenteritis. PMID- 17334418 TI - Fluoroscopy guided chemical lumbar sympathectomy for lower limb ischaemic ulcers. AB - The purpose of this study was to assess the effectiveness of chemical lumbar sympathectomy in relieving pain and healing ischaemic ulcers in patients with peripheral vascular diseases. Thirty-one consecutive patients with ischaemic/ gangrenous lower limb ulcers, referred to the BPKIHS, Pain Clinic were observed prospectively after chemical lumbar sympathectomy using modified Reid Technique with 3 ml of 70% alcohol each at L2 and L3 level under fluoroscopic guidance. Pain relief and ulcer healing were noted in the follow up. Moreover, patients' abilities to resume at least part of their day to day work were also noted at three months follow up. Of the total 31 patients, 16 had Buerger's disease and the remaining 15 had non-Buerger's ischaemic ulcers of which 7 were diabetic. There was significant decrease in the pain score from mean+/-SD of 8.3+/-0.9 (pre block) to 4.2+/-2.5 (post-block after 3 days) in zero to 10 Numerical Analogue Scale (NAS). By 3 months, 6 patients declined for follow up; 19(76%) of the remaining 25 patients reported pain relief, 18(72%) reported healing or decrease in the size of ulcers and 11(44%) were able to resume at least part of their usual work. Minor complications occurred in 5 patients and amputation was needed in 6 patients. Fluoroscopy- guided chemical lumbar sympathectomy is feasible, safe and effective in relieving pain and promoting ulcer healing in patients with ischaemic lower limb ulcers due both to Buerger's disease and non-Buerger's peripheral vascular diseases. PMID- 17334419 TI - Burn injuries in pediatric population. AB - Burn injuries constitute a major concern in the pediatric age group with respect to morbidity and mortality particularly in children in developing countries. Burn injuries represent an extremely stressful experience for both the burn victims as well as their families. Burn injuries are least explored areas among other injuries in Nepal. We do not have any data on childhood burn injuries and this study is done to know the incidence, age, sexwise distribution and nature of childhood burn injuries at Patan Hospital. Hospital based prospective study done at Emergency and surgical department during one year period. Twenty children that had fulfilled hospital criteria for admission included in this study. All injuries were of accident in nature. Scald injuries were more than dry burn injuries. Children less than 5 years were more prone to injury than older children. Twenty one patients survived after treatment and one patient died due to sepsis. Mortality in this series is about four percent. Burn injury is a leading cause of unintentional injuries mainly seen in children less than 5 years of age with physical as well as psychological consequences. PMID- 17334420 TI - Association of lipid profile and body mass index (bmi) in hypertensive patients of Eastern Nepal. AB - Dyslipidemia is closely associated with hypertension. Out of different fractions of lipoprotein, definite association of elevated LDL-Cholesterol (LDLc) and other lipid parameters has been well observed in hypertensive patients. The present cross sectional study was undertaken at BP Koirala Institute of Health Sciences with the aim to find out association of different lipid parameters and Body Mass Index (BMI) among newly diagnosed hypertension without any medications in Eastern Nepal. 80 hypertensive patients fulfilling JNC-7 criteria and 80 healthy controls were enrolled in this study. Lipid parameters (TC, TG, LDLc, VLDLc, HDLc) were estimated by Enzymatic Colorimetric test. Quetlet's formula was used to calculate BMI. Results were analyzed with student's 't' test and Pearson correlation analysis. Mean age of patients and controls were 36.30 +/- 7.73 yrs & 32.13 +/- 7.21 yrs respectively. There was significant increase in different lipid parameters namely TC (170.18 22.53 vs 145.23 21.13,P<0.005), TG (146.60 53.87 vs 119.77 35.61, P<0.005), LDLc (100.71 23.74 vs 79.25 20.10,P<0.05) and VLDLc (29.32 1077 vs 23.92 7.12, P<0.05) in patients as compared to the healthy controls. However there was no any significant difference in HDLc value. Pearson correlation analysis shows positive correlation of BMI with all the four lipid parameters even though it was not statistically significant. Thus this study shows direct association of BMI, dyslipidemia in hypertensive patients of the Eastern Nepal. PMID- 17334421 TI - Abnormal spicules on the inferior aspect of anterior arch of atlas vertebra. AB - Anterior arch of the atlas vertebra is known to exhibit various developmental anomalies. Bony outgrowths, osteophytes, clefts and aplasia of the anterior and posterior arches of the atlas have received special attention by research workers. To the best of our knowledge, not many osteological studies have defined the spicules on the anterior arch of the atlas. The present study describes an abnormal atlas vertebra with 2 spicules on the inferior aspect, 2 additional facets inferior to the superior articular facets and a peculiar facet to the left of the posterior tubercle. These abnormal spicules may cause dysphagia or involve atlanto-occipital movements. Such anomalies may be misinterpreted in routine X rays as a degenerative disease. However, asymptomatic cases remain undetected throughout life. Such anomalies may be important in radiological, clinical, forensic and anthropological studies. PMID- 17334422 TI - Medial peritalar dislocation in a volleyball player. AB - We report a medial peritalar dislocation, which was treated with closed reduction and cast for 3 weeks. At follow up 12 months later, there was normal range of motion and mild pain after prolonged walking. PMID- 17334423 TI - Practice in anesthesia: intrathecal morphine for off pump coronary artery bypass graft. AB - Off pump coronary artery bypass grafting is gaining popularity because of its beneficial effects like reduced inflammatory response, early extubation, reduced hospital & ICU stay, less homologous blood transfusion & reduced cost. Here we report a case of left anterior descending artery blockade who had undergone off pump coronary artery bypass grafting. In this case we used intrathecal morphine with heavy bupivcaine to provide intraoperative as well as post operative analgesia. Though intrathecal morphine has been used as analgesia in cardiac surgeries, the use of intrathecal morphine with bupivacaine is less reported. It not only provides intense analgesia which helps for early extubation & hemodynamic stability but also provides calm & quiet surgical field with slow beating heart & aids in critical time of vessel anastomosis. We have also discussed the other aspects of anesthetic management with little elaboration in surgical aspect as well. PMID- 17334424 TI - Simultaneous pancreas and kidney transplantation for end-stage renal failure secondary to diabetic nephropathy : principles and practice. AB - Diabetic nephropathy is the second most common cause of renal failure in the United Kingdom where majority of the patients were managed by renal transplantation and insulin therapy in the past. Over the last three decades, increasing number of patients are undergoing simultaneous pancreas and kidney transplantation (SPKT) because of its advantages, which renders the patient both dialysis and insulin-independent, halts the progression of complications of diabetes, thereby improves the quality of life, survival and has proven to be cost-effective. This article presents a review on the principles and contemporary practice of SPKT worldwide and highlights the future directions. PMID- 17334425 TI - Single-scan extraction of two-dimensional parameters of infrared focal plane arrays utilizing a Fourier-transform spectrometer. AB - We present what is believed to be a novel experimental method to measure the technological parameters (spectral response and quantum yield) of an infrared focal plane array. This method makes original use of a Fourier transform spectrometer, which allows us to simultaneously extract the spectral performances of all pixels from one single set of measurements. The methodology used and the principle of the experimental setup are detailed. A Fourier analysis is shown to provide various optogeometrical information on the detector microstructure. A demonstrator based on the HgCdTe technology was designed, and satisfactory experimental results were obtained. PMID- 17334426 TI - Diffraction by dual-period gratings. AB - The dynamical characteristics of dual-period perfectly conducting gratings are explored. Gratings with several grooves (reflection) or slits (transmission) within each period are considered. A scalar approach is proposed to derive the general characteristics of the diffracted response. It was found that compound gratings can be designed to cancel as well as to intensify a given diffraction order. These preliminary estimations for finite gratings are validated by numerical examples for infinitely periodic reflection and transmission gratings with finite thickness, performed using an extension of the rigorous modal method to compound gratings, for both polarization cases. PMID- 17334427 TI - Simultaneous temperature and strain measurements performed by a step-changed arc induced long-period fiber grating. AB - A compact sensor based on step-changed arc-induced long-period fiber gratings was implemented to discriminate between temperature and strain. The proposed sensor consists of a single long-period grating with two sections written consecutively in the SMF-28 fiber using the electric arc discharge technique. The two sections have the same period but different fabrication parameters. The operation of the sensor relies on the existence of a difference between the values of temperature and strain sensitivity of two neighboring resonances observed in the spectrum of the step-changed grating. The temperature and strain resolutions obtained for the sensor are 0.2 degrees C and 35 micro epsilon, respectively. PMID- 17334428 TI - Behavior of imperfect band-limited coronagraphic masks in a high-contrast imaging system. AB - We investigate the behavior of imperfect band-limited occulting masks in a high contrast imaging system through modeling and simulations. Grayscale masks having 1D Sinc(2) (linear-Sinc(2)) amplitude transmission coefficient (Sinc(4) intensity transmittance) profiles as well as optical density and wavelength-dependent parasitic phases are considered occulters. We compare the behaviors of several, slightly different occulter transmittance profiles by evaluating the contrast performance of the high-contrast imaging testbed (HCIT) at the Jet Propulsion Laboratory (JPL). These occulters include a measured occulter, a standard Sinc(2) occulter, and several of its variations. We show that when an occulting mask has a parasitic phase, a modified Sinc(2) transmittance profile works much better than the standard Sinc(2) mask. We examine the impact of some fabrication errors of the occulter on the HCIT's contrast performance. We find through modeling and simulations that starlight suppression by a factor of more than 10(10) is achievable at least monochromatically on the HCIT with the occulting mask and the optics currently being used on the testbed. To the best of our knowledge, this is the first time that we investigate the behavior of a real (or fabricated) focal plane occulting mask in a high-contrast imaging system. We also briefly describe the approach used at JPL in fabricating a grayscale occulting mask and characterizing its transmittance and phase profiles. PMID- 17334429 TI - Correction of the Preston equation for low speeds. AB - According to Preston [J. Soc. Glass Technol. 11, 214 (1927)], the wear on a glass point in the polishing process is proportional to the work given by frictional force between glass and tool. He supposed that the frictional coefficient is a constant value. To verify this hypothesis, we measured the dragging forces applied to a tool as a function of the relative speed between a rotating glass and the tool center. To reproduce these experimental results, it was necessary to propose a new model, for which the frictional coefficient has a Gaussian dependence with relative speed. Therefore the wearing Preston equation has to be modified in order to include the frictional coefficient as a function of the relative speed. PMID- 17334430 TI - Wavefront error measurement of high-numerical-aperture optics with a Shack Hartmann sensor and a point source. AB - We developed a new, to the best of our knowledge, test method to measure the wavefront error of the high-NA optics that is used to read the information on the high-capacity optical data storage devices. The main components are a pinhole point source and a Shack-Hartmann sensor. A pinhole generates the high-NA reference spherical wave, and a Shack-Hartmann sensor constructs the wavefront error of the target optics. Due to simplicity of the setup, it is easy to use several different wavelengths without significant changes of the optical elements in the test setup. To reduce the systematic errors in the system, a simple calibration method was developed. In this manner, we could measure the wavefront error of the NA 0.9 objective with the repeatability of 0.003 lambda rms (lambda = 632.8 nm) and the accuracy of 0.01 lambda rms. PMID- 17334431 TI - Ellipsometric determination of polarization-dependent transmission in resonant feedback systems. AB - The polarization-dependent transmission of a basic anisotropic feedback system (Fabry-Perot resonator) is mathematically modeled by means of the Jones-matrix formalism. Detailed numerical simulations of the resonance case are performed. Small phase anisotropies as well as small polarization-dependent losses of the resonator components can be extremely amplified by resonant feedback. The amplification factors depend on the magnitudes of amplitude and phase anisotropy and their mutual interactions as well as on the polarization-independent system parameters (forward transmission, system feedback). However, for higher phase anisotropies, saturation effects occur and, therefore, the anisotropy amplification factors decrease. Our experimental investigations applying anisotropic Fabry-Perot resonators in different ellipsometer systems confirm the predicted amplification of phase and loss anisotropies in resonance operation. PMID- 17334432 TI - Modeling of evanescent coupling between two parallel optical nanowires. AB - Evanescent coupling between two parallel nanowires is investigated using the finite-difference time-domain method. Silica, tellurite, and silicon nanowires are used as typical materials in the simulation. Compared with weakly coupled waveguides, strongly coupled nanowires show much smaller transfer lengths without sacrificing high coupling efficiencies, suggesting possibilities for developing highly compact evanescent-coupling-based nanowire photonic devices, as well as for achieving high-efficiency interconnection between nanowires and external optical systems. Meanwhile, the polarization-dependent coupling properties, the considerably high minimum coupling efficiency, and the supermode-cutoff-like behavior are also observed. Evanescent coupling properties of strongly coupled nanowires demonstrated may provide valuable references for practical applications of optical nanowires. PMID- 17334433 TI - Simple technique for the generation of plane surface normal to optic axis direction of uniaxial crystal. AB - What we believe to be a new experimental technique for the generation of a plane crystal surface perpendicular to the optic axis direction of a transparent birefringent uniaxial crystal is presented. A simple setup has been described for the initial optic axis alignment of a raw uniaxial crystal blank. Error correction methods have been illustrated. A technique for producing high optical quality surfaces by block polishing plane parallel crystal surfaces normal to the direction of the optic axis, in one setting, is discussed. The block with angular graduations facilitates the correction of angular error. A new conoscopy setup has been coupled to a Fizeau interferometer for high accuracy testing of the optic axis alignment with respect to the surface normal of the relevant polished surface of the uniaxial crystal. The results obtained for a quartz crystal blank are presented. PMID- 17334434 TI - Performance study of Kalman filter controller for multiconjugate adaptive optics. AB - We compare the performance of the Kalman filter (KF)-based and the minimum variance (MV) control algorithms for a zonal adaptive optics with a phase temporal prediction step included for effective compensation of the errors attributable to latencies in the system. The main goal is to evaluate the performance achievable by the computationally more expensive KF approach, which explicitly accounts for the atmospheric turbulence temporal behavior through a first-order autoregressive evolution model, and the simpler MV algorithm, with and without temporal prediction. For a representative example, the Gemini-South 8 m telescope multiconjugate adaptive optics system performance of the KF and the MV controllers has been compared with respect to their turbulence compensation capability. We show that the KF algorithm, as expected, shows superior performance to that of the MV algorithm, especially for extremely low sampling rates and large control latencies. We also show that for moderate control latencies the MV algorithm with a temporal prediction step added to it approaches the performance of the KF technique. PMID- 17334435 TI - Volume-holographic filters for rotational sensing of three-dimensional objects. AB - A highly precise rotational filter based on a volume-holographic optical element is proposed and demonstrated. We present a clear theoretical calculation of the rotation sensitivity of the volume-holographic filter used to sense the rotation of a spherical ground glass object. By introducing the longitudinal displacement of the scattering point across the sphere, the sensitivity of the filter is greatly improved to 350 times that of a general case for a planar ground glass. PMID- 17334436 TI - Three-dimensional shift selectivity in reflection-type holographic disk memory with speckle shift recording. AB - Three-dimensional shift selectivity of a reflection-type hologram with speckle shift recording is investigated experimentally and numerically. We build an experimental setup consisting of lenses with numerical apertures of 0.28 and an iron-doped LiNbO(3) with a thickness of 0.5 mm. The experimental results show that three-dimensional selectivity has a size of 0.97 microm x 0.97 microm x 8.8 microm in diffraction efficiency. We also develop a volume holographic memory simulator to evaluate the experimental results. The simulator can quantitatively evaluate bit error rate, signal-to-noise ratio, and diffraction efficiency. Numerical results are in good agreement with the experimental results. The experimental and numerical results indicate that three-dimensional shift multiplexing can increase the storage capacity. PMID- 17334438 TI - Method for calculating the coupling coefficient in step-index optical fibers. AB - A simple method is proposed for determining the mode coupling coefficient D in step-index multimode optical fibers. It only requires observation of the far field output pattern for one fiber length with the input light launched centrally along the fiber axis (theta(0)=0). For illustration, the coupling coefficient determined by this simple method for a step-index plastic optical fiber was used to calculate the coupling length L(c) at which the equilibrium mode distribution is achieved, and length z(s) at which the steady-state distribution is achieved. Our results are in good agreement with experimental results reported earlier. PMID- 17334437 TI - Image scale determination for optimal texture classification using coordinated clusters representation. AB - The efficiency of texture image classification is certainly influenced by image scale when a feature space or a classification method is not scale invariant. An alternative approach to the scale-invariant techniques is proposed that first estimates an effective image scale and then uses it to adjust texture features to get the best possible texture image recognition and classification. We use the correlation distance between pixels as a measure of the scale of texture images. We study the performance of classification of texture images in the coordinated cluster representation (CCR) versus an image scale and the size of the scanning window used for the coordinated cluster transform. Given the number of classes to be classified in, we find that an optimal (up to 100%) classification efficiency in the CCR feature space is obtained by changing an image scale and/or the size of the scanning window in the coordinated cluster transform. PMID- 17334439 TI - Stabilization of electro-optic modulator bias voltage drift using a lock-in amplifier and a proportional-integral-derivative controller in a distributed Brillouin sensor system. AB - In a distributed Brillouin sensor system, it is crucial to keep the pulse energy uniform for a constant signal-to-noise ratio. This means that the variable dc leakage (pulse base) for the electro-optic modulator (EOM) must be locked. We examine two different methods of locking the EOM bias voltage and look at the advantages and disadvantages of each locking method. It is found that the two locking methods, one based on a lock-in amplifier and the other using proportional-integral-derivative control, both have applications in which they excel at locking the pulse base. PMID- 17334440 TI - Self-mixing interferometry based on a double-modulation technique for absolute distance measurement. AB - A new, to the best of our knowledge, method for the measurement of the absolute distance of a remote target based on the laser diode self-mixing interferometry is presented. A double-modulation technique is introduced to improve the measurement resolution. Wavelength modulation of the laser beam is obtained by modulating the injection current of the laser diode. Phase modulation of the laser beam is obtained by an electro-optic crystal in the external cavity. Absolute distance of the external target is determined by the Fourier analysis method. Theoretical analysis and numerical simulations are given. Experimental results show that a resolution of +/-0.3 mm can be achieved for absolute distance ranging from 277 to 477 mm. PMID- 17334441 TI - Accurate sensitivity analysis of photonic devices exploiting the finite difference time-domain cavity adjoint variable method. AB - For what is believed to be the first time, the central adjoint variable method (CAVM) is applied to the sensitivity analysis of photonic devices using the finite-difference time-domain (FDTD) technique. The FDTD-CAVM technique obtains accurate sensitivities of any desired response with respect to the different design parameters. Our technique requires only one extra FDTD simulation to extract the sensitivities with respect to all the design parameters regardless of their number. Cost-free sensitivities of the power reflectivity are also derived without any additional simulation. The results show a very good agreement between the CAVM sensitivities and those obtained using the expensive central finite difference approximation. PMID- 17334442 TI - Development of a chirped pulse amplification laser with zigzag slab Nd:glass amplifiers dedicated to x-ray laser research. AB - A chirped pulse amplification laser with zigzag slab Nd:glass amplifiers dedicated to x-ray laser research is described. The laser provides a 1.6 ps duration pulse with approximately 7 J energy at a repetition rate of 0.1 Hz. In the power amplifier system, laser light is amplified in a two-step manner: The first step is image-relayed multipass amplification up to approximately 1 J with a 10 mm x 10 mm beam. The second step is double-pass amplification up to >10 J with a 10 mm x 90 mm beam. By using this laser system, the saturated amplification of the Ni-like Ag laser at a wavelength of 13.9 nm has been successfully demonstrated. PMID- 17334443 TI - Photoluminescence and lasing from deoxyribonucleic acid (DNA) thin films doped with sulforhodamine. AB - Thin solid films of salmon deoxyribonucleic acid (DNA) have been fabricated by treatment with a surfactant and used as host for the laser dye sulforhodamine (SRh). The DNA films have an absorption peak at approximately 260 nm owing to absorption by the nitrogenous aromatic bases. The SRh molecules in the DNA films have absorption and emission peaks at 578 and 602 nm, respectively. The maximum emission was obtained at approximately 1 wt. % SRh in DNA, equivalent to approximately 100 DNA base pairs per SRh molecule. A distributed feedback grating structure was fabricated on a SiO(2)-Si substrate using interference lithography. The grating period of 437 nm was selected, corresponding to second-order emission at the amplified spontaneous emission wavelength of 650 nm. Lasing was obtained by pumping with a doubled Nd:YAG laser at 532 nm. The lasing threshold was 3 microJ, corresponding to approximately 30 microJ/cm(2) or 4 kW/cm(2). The emission linewidth decreased from approximately 30 nm in the amplified spontaneous emission mode to <0.4 nm (instrument limited) in the lasing mode. The slope efficiency of the lasing was approximately 1.2%. PMID- 17334444 TI - Accurate modeling of dielectric interfaces by the effective permittivities for the fourth-order symplectic finite-difference time-domain method. AB - The fourth-order finite-difference time-domain (FDTD) method using a symplectic integrator propagator can calculate the propagation of the electromagnetic waves with very low dispersion error in the region of a constant or smoothly varying index profile. An additional technique is required for the problem with the discontinuous dielectric interfaces. We derived the third-order effective permittivities at dielectric interfaces for the fourth-order FDTD method in the case of 2D TE polarization. As the required accuracy level is increased, the memory resources used by the fourth-order FDTD method with the effective permittivities are reduced severalfold or more compared with the standard FDTD method. The accurate performance of the proposed method is demonstrated through numerical examples. PMID- 17334445 TI - Assessment of the Moderate-Resolution Imaging Spectroradiometer algorithm for retrieval of aerosol parameters over the ocean. AB - The Moderate Resolution Imaging Spectroradiometer aerosol algorithm over the ocean derives spectral aerosol optical depth and aerosol size parameters from satellite measured radiances at the top of the atmosphere (TOA). It is based on the adding of apparent optical properties (AOPs): TOA reflectance is approximated as a linear combination of reflectances resulting from a small particle mode and a large particle mode. The weighting parameter eta is defined as the fraction of the optical depth at 550 nm due to the small mode. The AOP approach is correct only in the single scattering limit. For a physically correct TOA reflectance simulation, we create linear combinations of the inherent optical properties (IOPs) of small and large particle modes, in which the weighting parameter f is defined as the fraction of the number density attributed to the small particle mode. We use these IOPs as inputs to an accurate multiple scattering radiative transfer model. We find that reflectance errors incurred with the AOP method are as high as 30% for an aerosol optical depth of 2 at 550 nm. The retrieved optical depth has a relative error of up to 8%, and the retrieved fraction eta has an absolute error of approximately 6%. We show that the use of accurate radiative transfer simulations and a bimodal fraction f yields accurate values for the retrieved optical depth and the fraction f. PMID- 17334446 TI - Remote sensing of the ocean contributions from ultraviolet to near-infrared using the shortwave infrared bands: simulations. AB - In the remote sensing of the ocean near-surface properties, it is essential to derive accurate water-leaving radiance spectra through the process of the atmospheric correction. The atmospheric correction algorithm for Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) and Moderate Resolution Imaging Spectroradiometer (MODIS) uses two near-infrared (NIR) bands at 765 and 865 nm (748 and 869 nm for MODIS) for retrieval of aerosol properties with assumption of the black ocean at the NIR wavelengths. Modifications are implemented to account for some of the NIR ocean contributions for the productive but not very turbid waters. For turbid waters in the coastal regions, however, the ocean could have significant contributions in the NIR, leading to significant errors in the satellite-derived ocean water-leaving radiances. For the shortwave infrared (SWIR) wavelengths (approximately > 1000 nm), water has significantly larger absorption than those for the NIR bands. Thus the black ocean assumption at the SWIR bands is generally valid for turbid waters. In addition, for future sensors, it is also useful to include the UV bands to better quantify the ocean organic and inorganic materials, as well as for help in atmospheric correction. Simulations are carried out to evaluate the performance of atmospheric correction for nonabsorbing and weakly absorbing aerosols using the NIR bands and various combinations of the SWIR bands for deriving the water-leaving radiances at the UV (340 nm) and visible wavelengths. Simulations show that atmospheric correction using the SWIR bands can generally produce results comparable to atmospheric correction using the NIR bands. In particular, the water-leaving radiance at the UV band (340 nm) can also be derived accurately. The results from a sensitivity study for the required sensor noise equivalent reflectance, (NE Delta rho), [or the signal-to noise ratio (SNR)] for the NIR and SWIR bands are provided and discussed. PMID- 17334447 TI - Dust optical properties retrieved from ground-based polarimetric measurements. AB - We have systematically processed one year of sunphotometer measurements (recorded at five AERONET/PHOTONS sites in Africa) in order to assess mineral dust optical properties with the use of a new polarimetry-based algorithm. We consider the Cimel CE318 polarized sunphotometer version to obtain single-scattering albedo, scattering phase matrix elements F(11) and F(12) for dust aerosols selected with Angstrom exponents ranging from -0.05 to 0.25. Retrieved F(11) and F(12) differ significantly from those of spherical particles. The degree of linear polarization -F(12)/F(11) for single scattering of atmospheric total column dust aerosols in the case of unpolarized incident light is systematically retrieved for the first time to our knowledge from sunphotometer measurements and shows consistency with previous laboratory characterizations of nonspherical particles. PMID- 17334448 TI - Refractometry of organosilica microspheres. AB - The refractive index of novel organosilica (nano/micro) material is determined using two methods. The first method is based on analysis of optical extinction efficiency of organosilica beads versus wavelength, which is obtained by a standard laboratory spectrometer. The second method relies on the measurable trapping potential of these beads in the focused light beam (laser tweezers). Polystyrene beads were used to test these methods, and the determined dispersion curves of refractive-index values have been found accurate. The refractive index of organosilica beads has been determined to range from 1.60 to 1.51 over the wavelength range of 300-1100 nm. PMID- 17334449 TI - Electromagnetic phase differences in the coherent backscattering enhancement mechanism for random media consisting of large nontransparent spheres. AB - Phase curves of intensity are calculated for light scattering in media randomly packed with large nontransparent spheres (x=125), the surfaces of which reflect according to the Fresnel equations. We consider three values of refractive index: m = 0.73 + i5.93 (metal Al), 1.6 + i1.72 (metal Fe), and 1.5 + i0.1 (black glass). We use a Monte Carlo ray-tracing approach. Different kinds of electromagnetic phase differences of reciprocal trajectories are investigated for the second and third orders of scattering; the highest orders give comparatively small contributions due to the backward-scattering indicatrix of large nontransparent spheres. We find that the main electromagnetic phase difference between the direct and time-reversal (reciprocal) trajectories is the outer phase difference that depends only on the relative positions of the first and last points of the ray reflections and the phase angle. The inner phase difference is connected with the changing path length of the ray inside the medium. This depends on the particle size and the phase angle that is the angle between the source and receiver from the scatterer, i.e., 180 degrees minus the scattering angle. The inner phase difference can give oscillations in the phase curve consisting of second-order components if the medium consists of strictly monodisperse spheres. Usually the coherent backscattering enhancement is calculated ignoring the shadow-hiding effect. We show that accounting for the shadowing of the reciprocal trajectory is important for the formation of the backscattering effect. The third-order scattering surge is a superposition of wide and narrow opposition spikes that correspond to two different types of scattering trajectories, closed and opened ones. The first type is due to scattering by two particles; the second one corresponds to scattering by three particles. PMID- 17334450 TI - Chromatism compensation of the PETAL multipetawatt high-energy laser. AB - High-energy petawatt lasers use series of spatial filters in their amplification section. The refractive lenses employed introduce longitudinal chromatism that can spatially and temporally distort the ultrafast laser beam after focusing. To ensure optimum performances of petawatt laser facilities, these distortions need to be corrected. Several solutions using reflective, refractive, or diffractive optical components can be addressed. We give herein a review of these various possibilities with their application to the PETAL (Petawatt Aquitaine Laser at the Laser Integration Line facility) laser beamline and show that diffractive based corrections appear to be the most promising. PMID- 17334451 TI - Simulation of an absorption-based surface-plasmon resonance sensor by means of ellipsometry. AB - Through numerical simulations, we point out that introduction of an ellipsometric measurement technique to an absorption-based surface-plasmon resonance (SPR) sensor enhances precision and sensitivity in measuring the imaginary part k of the complex refractive index of the sample. By measuring a pair of ellipsometric Delta-Psi parameters, instead of the conventional energy reflectance R(p) of p polarized light in the Kretschmann optical arrangement, we can detect a small change of k that is proportional to that of the concentration of the sample, especially when k << 1. While one has difficulty in determining the value of k uniquely by the standard technique, when the thickness of Au under the prism is thin (20-30 nm), the ellipsometric technique (ET) overcomes the problem. Furthermore, the value of k and the thickness d(s) of the absorptive sample that is adsorbed on Au can be determined precisely. The ET based on the common-path polarization interferometer is robust against external disturbance such as mechanical vibration and intensity fluctuation of a light source. Although only the p-polarized light is responsible for the SPR phenomenon, we show that the introduction of the ET is significant for quantitative analysis. PMID- 17334452 TI - "The Golden Rule": Only a starting point for quality care. AB - The Golden Rule guides people to choose for others what they would choose for themselves. The Golden Rule is often described as 'putting yourself in someone else's shoes', or 'Do unto others as you would have them do unto you'(Baumrin 2004). The viewpoint held in the Golden Rule is noted in all the major world religions and cultures, suggesting that this may be an important moral truth (Cunningham 1998). The Golden Rule underlies acts of kindness, caring, and altruism that go above and beyond "business as usual" or "usual care" (Huang, 2005). As such, this heuristic or 'rule of thumb' has universal appeal and helps guide our behaviors toward the welfare of others. So why question the Golden Rule? Unless used mindfully, any heuristic can be overly-simplistic and lead to unintended, negative consequences.A heuristic is a rule of thumb that people use to simplify potentially overwhelming or complex events. These rules of thumb are largely unconscious, and occur irrespective of training and educational level (Gilovich, Griffin & Kahneman 2002). Rules of thumb, such as the Golden Rule, allow a person to reduce a complex situation to something manageable-e.g., 'when in doubt, do what I would want done'. Because it is a simplifying tool, however, the Golden Rule may lead to inappropriate actions because important factors may be overlooked.In this article we describe "The Golden Rule" as used by administrators, supervisors, charge nurses, and CNAs in case studies of four nursing homes. By describing use of this rule-of-thumb, we aim to challenge nurses in nursing homes to: 1) be mindful of their use of "The Golden Rule" and its impact on staff and residents; and 2) help staff members think through how and why "The Golden Rule" may impact their relationships with staff and residents. PMID- 17334453 TI - Pericardial pathology 900 years ago. A study and translations from an Arabic medical textbook. AB - This is a study and translation of the section on pericarditis in Al Taisir book written by the Muslim physician Ibn Zuhr Avenzoar who lived and practiced in Eshbeelia nowadays Seville, Andalusia, Spain between 1091-1162 AD. Ibn Zuhr described the serous type of pericarditis as well as the pathological findings in fibrinous pericarditis. His description of the latter may also fit with the picture of chronic fibrous pericarditis. He also described acute purulent pericarditis and involvement of the pericardium in cases of acute carditis with hectic fever. Ibn Zuhr's description of the pericardial effusion in serous pericarditis as looking like urine indicates that he must have seen a sample of the fluid obtained either by pericardiocentesis or during a post-mortem examination. However, his description of solid substances accumulating on the inside of the hearts covering looking like layers upon layers of membranes could not have been made possible without post-mortem dissection. PMID- 17334454 TI - The role of human papillomavirus infection in prostate cancer. AB - Human papillomavirus HPV is the cause of the most common sexually transmitted diseases STDs of viral etiology worldwide. High-risk HPVs are the etiological agents of cervical and other anogenital malignancies and low-risk HPVs induce only benign genital warts. Since high-risk HPVs have been shown to possess oncogenic potential, an association between HPV infection and prostatic carcinoma Pca has been suggested. Some authors demonstrated that HPV infection play an important role in the pathogenesis of Pca. Active research is ongoing to highlight the mechanisms by which HPV involved in the development of cancer. The aim of this article is to review the studies that investigated the association between HPV and Pca and to explore the mechanism of HPV oncogenesis. PMID- 17334455 TI - Immunohistochemical localization of extracellular matrix proteins in developing lung tissues. AB - OBJECTIVE: To examine the laminin specific receptor, known as beta1 integrin, and fibronectin distributions in 13, 15, 17, and 20 days prenatally old and 2 and 6 days postnatally old murine lung tissue by immunohistochemical methods at light microscope level. METHODS: Male and female swiss albino mice were used for experimental procedures from July 2001 to March 2002 at Gazi University Faculty of Medicine. The study was conducted on samples of 13, 15, 17, and 20 prenatally old and 2 and 6 days postnatally old lung tissues. Indirect immunohistochemical methods and fibronectin and laminin beta1 integrin antibodies were used; tissues were examined with a light microscope. RESULTS: In the prenatal group, fibronectin immunoreactivity was determined to be irregular in bronchiole epithelium cells, while it was strongly evident in mesenchymal cells and vascular endothelial cells. Laminin beta1 integrin immunoreactivity was also observed irregularly. Development period of lungs, immunoreactivity of fibronectin was clearly identified in the bronchiolus, ductus alveolaris and alveolar epithelial cells, mesenchymal cells, and vascular endothelial cells, and laminin immunoreactivity was strongly involved both in the apical and basal membranes of all the epithelial cells and within the basal lamina. The decreased immunoreactivity of fibronectin and laminin beta1 integrin was established after birth on the fetal period. CONCLUSION: In this study we concluded: 1. During the development of the lung, fibronectin is necessary for the shaping of lung parenchyma and stroma. 2. beta1 integrin as the receptor of laminin is important in the process of lung maturation and the modelling of basal lamina. PMID- 17334456 TI - Hyperhomocysteinemia, coronary heart disease, and diabetes mellitus as predicted by various definitions for metabolic syndrome in a hypertensive Saudi population. AB - OBJECTIVE: From the emergence of different definitions of metabolic syndrome (MS) we aim to determine the prevalence of such a condition among hypertensive Saudi population and to identify which definition can best assess the risk of hyperhomocysteinemia, coronary heart disease (CHD), and diabetes mellitus. METHODS: In this cross-sectional study, we studied 581 hypertensive Saudis, aged 21-70, at the King Abdul-Aziz University Hospital, from June 2005 to December 2005 Each participant completed the questionnaire and underwent a complete physical examination. Metabolic parameters were measured using routine laboratory procedures and homocysteine using HPLC by the electrochemical detection method. RESULTS: According to the International Diabetes Federation (IDF) definition we diagnosed 222 males and 256 females. There is an increased risk for hyperhomocystenemia using the Adult Treatment Panel III (ATPIII) guidelines (odds ratio [OR] 3.30, 95% confidence interval [CI] 0.87-12.56; p=0.08) compared to IDF (OR 0.59, CI 0.17-2.10; p=0.41) and WHO (OR 0.45, CI 0.16-1.25; p=0.12); increased risk for probable CHD in patients with MS by WHO (OR 2.17, CI 1.11 4.25; p=0.02) compared to ATPIII (OR 2.14, CI 1.05-4.35; p=0.035) and IDF (OR 0.81, CI 0.37-1.78; p=0.6); risk of DM is highest with IDF (OR 13.07, CI 1.66 102.94; p=0.015). CONCLUSION: There is a high prevalence of MS among hypertensive Saudis regardless of definition used; it is most prevalent using the IDF definition as well as the risk for diabetes Patients diagnosed with ATPIII guidelines have greater risk of hyperhomocysteinemia. We recommend the WHO definition for Arabs since it predicts increased risk for CHD. PMID- 17334457 TI - Gadolinium chloride attenuates aortic occlusion-reperfusion-induced myocardial injury in rats. AB - OBJECTIVE: Aortic ischemia and reperfusion periods, which are often associated with infrarenal abdominal aortic cross-clamping and declamping, cause injury in distant organs including the heart. We recently reported that Kupffer cell blockage with gadolinium chloride (GdCl3) attenuates lung injury induced by aortic ischemia-reperfusion (IR). Therefore, we hypothesized that GdCl3 may attenuate myocardial injury induced by aortic IR. METHODS: The study was carried out in June 2005, in the Laboratory of Experimental Studies of Suleyman Demirel University Medical School, Isparta, Turkey. We studied the effect of GdCl3 on myocardial injury induced by abdominal aortic occlusion-reperfusion in rats by measuring the tissue levels of superoxide dismutase, catalase, malondialdehyde and activity of myeloperoxidase in rat heart specimens. Wistar-Albino rats (8 per group) were randomized into 3 groups. The control group underwent midline laparotomy and dissection of the infrarenal abdominal aorta without occlusion; the aortic IR group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 minutes followed by 60 minutes of reperfusion; and the GdCl3 + aortic IR group was pretreated with intravenous GdCl3 10 mg/kg 24 hours before the aortic IR. RESULTS: Aortic IR significantly increased whereas pretreatment with GdCl3 significantly decreased oxygen free radical production, lipid peroxidation and neutrophil activation in the heart tissues of the rats. CONCLUSION: Our results indicate that Kupffer cell blockage with GdCl3 attenuates the myocardial injury induced by aortic IR. We think that the novel findings of the present study may be a basis for further studies investigating the role of GdCl3 pretreatment in reducing myocardial morbidity and mortality caused by aortic IR during aortic surgery. PMID- 17334458 TI - A stereological and histological analysis of spleen on obese female rats, fed with high fat diet. AB - OBJECTIVE: To determine if there is an association between fatty diet induced obesity and spleen enlargement by means of Cavalieri principle, unbiased stereological method and light microscopic examination. METHODS: In this study, we used 16 adult female Sprague Dawley rats, weighing between 150-200 g. All animals were obtained from the Ataturk University Experimental Research and Applying Center, Turkey in 2005. We performed rat models, fed with normal or high fat diet for duration of 3 months. After this controlled nutritional process, spleens are removed from all anesthetized rats and performed by routine histological process. Stereologically, we estimated the spleen volumes in consecutive serial sections using Cavalieri method in control and treatment groups. Then, we examined histologically all those sections by a light microscope with camera attachment. RESULTS: Mean spleen volumes were 1.40 ml in the control and 2.03 ml in the treatment group, suggesting splenomegaly. Volumes of spleens in 2 groups revealed statistical significant difference (p<0.05, independent samples t-test). In studying spleen slices, many macrophages and necrotic figures were defined. Also, sinusoidal dilatation and hemosiderin deposits were observed and we found macrophages, filled with hemosiderin droplets. In some sections, especially around small vessels, eosinophilic aggregations and lipid accumulations in dilated sinusoids were detected. CONCLUSION: Spleen enlargement at significant levels (38%) in obese patients was determined by Cavalieri stereologic volume calculation method; an unbiased stereological method. Finally, our results clearly indicated that high fat diet caused to splenomegaly via sinusoidal dilatation and intra-cellular or intercellular deposits. PMID- 17334459 TI - Hemodynamic effects, recovery profiles, and costs of remifentanil-based anesthesia with propofol or desflurane for septorhinoplasty. AB - OBJECTIVE: To compare hemodynamics, recovery profiles, postoperative side effects and costs of desflurane-remifentanil and propofol-remifentanil anesthesia for septorhinoplasty operations. METHODS: A prospective and randomized study was carried out at the Gazi University Hospital, Ankara, Turkey from April to September 2003. Forty patients undergoing septorhinoplasty operations were randomly allocated to receive desflurane-remifentanil (Group DES-REM) or total intravenous anesthesia (TIVA) (Group TIVA). Anesthesia was induced in both groups with remifentanil 1 microg x ml (-1), propofol 2-2.5 mg.kg-1 and pancuronium 0.1 mg.kg-1. Maintenance was achieved with O2 50% in air at 4 L.min-1 and infusion of remifentanil 0.1 microg x ml (-1).min-1 in both groups. Group DES-REM received desflurane at 1 minimum alveolar concentration and Group TIVA received 10-4 mg.kg 1.hour-1 of propofol. Propofol infusion and desflurane were discontinued with the last surgical stitches, but remifentanil infusion continued in both groups until the nose was covered with plaster. Hemodynamic variables were recorded during the operation and one hour postoperatively in 5 min intervals. We recorded time of extubation, spontaneous eye opening and response to verbal commands times, visual analog scale pain scores, postoperative nausea and vomiting and Aldrete Recovery Score. Drug dosages and costs of each technique were determined. RESULTS: There were no statistically significant differences between the groups with respect to hemodynamic parameters, recovery profile, adverse effects, Aldrete Recovery Score and cost analysis. Visual analog scale at 5 min postoperatively was higher in group desflurane-remifentanil compared to group propofol-remifentanil (p<0.05). CONCLUSION: Both desflurane-remifentanil and TIVA provide perioperative hemodynamic stability, early and easy recovery with similar cost profiles for septorhinoplasty operations. PMID- 17334460 TI - Comparison of propofol/fentanyl and ketamine anesthesia in children during extracorporeal shockwave lithotripsy. AB - OBJECTIVE: Extracorporeal Shockwave Lithotripsy (ESWL) is an effective and safe way for treatment of upper urinary system stones. For pediatric patients, throughout ESWL, sufficient sedation and analgesia is needed to cope with the procedural pain. In this study, our goal was to compare 2 methods of intravenous anesthesia, applied to pediatric patients during ESWL. METHODS: Forty patients, between 3 months and 15 years of age who were admitted to the Faculty of Medicine, Hacettepe University, Turkey between September 2003 to September 2004 with upper urinary system calculi were randomized into 2 groups. All patients received intranasal midazolam 0.3 mg/kg premedication. Group K received intravenous (iv) ketamine 2 mg/kg; Group PF received a bolus of iv propofol 3 mg/kg and iv fentanyl 1 microg/kg along with a propofol infusion of 1 mg/kg/hr throughout the procedure. Procedural, recovery and discharge times, incidences of intra and post-procedural complications were compared. RESULTS: Demographics, procedural and discharge times were similar in 2 groups. While recovery times and post-procedural complication incidence was higher for the Group K, intra procedural complication incidence was higher for the Group PF. CONCLUSION: Although both protocols do not differ much according to ease of application and efficacy in providing sufficient analgesia for ESWL, they have their corresponding side effects and they can only be practiced safely by experienced anesthesiologists in a monitorized and well equipped setting. PMID- 17334461 TI - Pharmacoepidemiological study of prescription pattern of analgesics, antipyretics, and nonsteroidal anti-inflammatory drugs at a tertiary health care center. AB - OBJECTIVE: To examine the outpatients' prescribing pattern of doctors to analgesics, antipyretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) at a tertiary care setting in Southwestern Saudi Arabia. METHODS: A retrospective review of one-year outpatient prescriptions kept by the pharmacy department at Aseer Central Hospital during the period 8 April, 2000 until 7 April, 2001. Five working days per week of each season were sampled randomly and systemically as every other prescription. The type and number of drugs prescribed, patient's diagnoses and age, and the prescribing physician were analyzed. The study sample included 3796 prescriptions. RESULTS: There was no significant seasonal variation in the pattern of prescription. The most commonly prescribed agent was paracetamol followed in decreasing frequency by ibuprofen, diclofenac, and aspirin. In few of the prescriptions combination of analgesics, antipyretics, and NSAIDs were used. One fourth of prescriptions, the diagnosis was not mentioned or was not clearly written, infection in 40%, and musculoskeletal disorders in 17.7%. The rest were a variety of problems for some of which, the drugs were used inappropriately. Aspirin was used exclusively in adults for cardio-protection, while paracetamol was used mainly as analgesic-antipyretic over all age groups CONCLUSION: Some of prescriptions suffered from significant deficiencies. In light of the serious adverse effects of analgesics, antipyretics and NSAIDs, education of physicians on rational use of such drugs, and prescription writing seems necessary. PMID- 17334462 TI - Drug treatment modalities in patients with chronic osteoarthritis of the hip or knee. AB - OBJECTIVE: A survey was conducted to determine drug treatments taken by patients with chronic osteoarthritis (OA) of the hip or knee. METHODS: Data was collected at outpatient clinics at the Royal London and Newham University Hospitals, Bancroft Road, London between November 2001 and February 2003. RESULTS: Two hundred patients (mean age of 65.8 years, mean OA duration of 4.4 years) completed the survey; 175 with OA of knee and 25 with OA of hip. The majority of patients (64%) required a combination of drug treatments, either prescribed or self-medicated, to manage their disease. Of the total patients, 76% were taking paracetamol, 40% were taking an NSAID and 39% were taking complementary therapy (such as cod liver oil or glucosamine) either as monotherapy or in combination with other drugs. Of this patients 39% who previously used an NSAID had discontinued, primarily due to side effects, especially those of the gastrointestinal tract. CONCLUSION: The survey results demonstrate that there is a need to individualize treatment for each patient, which is consistent with published recommendations for the management of OA. PMID- 17334463 TI - Fast agar-based urease test for detection of Helicobacter pylori infection in the stomach. AB - OBJECTIVE: Helicobacter pylori (H. pylori) is an important etiological factor in the development of upper gastro intestinal tract (GIT) conditions. A variety of tests are now available to diagnose H. pylori infection but they require a relatively longer time to yield a definitive result. The present work describes fast agar-based urease (FABU) test for detection of the H. pylori in gastric biopsy. METHODS: One hundred and eighty-seven patients with upper GIT conditions were included in this study for the period from April 2003 to May 2004. One antral biopsy was taken from 100 patients while 2 antral biopsies were taken from 87 patients and inserted into FABU test, in addition to 3-4 biopsies were taken for histology examination. RESULTS: Using one antral biopsy, the FABU test correctly identified 65 of the 78 biopsies positive for H. pylori by histology (83.3%). There were 11 false negative (FN) and 3 false positive (FP). This yields sensitivity of 85.5% and specificity of 87.5%. While when 2 antral biopsies were used, the test correctly identified 61 of 64 H. pylori infected patients (92.2%). There were 3 FP and 5 FN. This yields sensitivity of 92.4% and specificity of 85.7%. Also, the result of this study revealed that 73.2% of the total patients included in this study were infected with H. pylori. Approximately 46.5% were males and 26.7% were females. CONCLUSION: The results of our study indicate that the FABU test is superior to other commercially available urease tests and provides rapid results of H. pylori status even before the patient is discharged from endoscopy suite. PMID- 17334464 TI - Helicobacter pylori cagA and iceA genotypes status and risk of peptic ulcer in Saudi patients. AB - OBJECTIVE: To determine the prevalence of cagA+ and iceA genotypes among Helicobacter pylori (H. pylori) isolates from a group of Saudi patients with gastric complaints, and to find out any significant correlation between these strains and severe gastric clinical outcomes such as peptic ulcer and gastric cancer in Saudi population. METHODS: A total of 1104 gastric biopsies from 368 patients who presented with symptoms suggestive of chronic gastritis, peptic ulcer disease, or gastric carcinoma were taken from the main hospitals in the Western region of Saudi Arabia from July 2004 to July 2005. We cultured the samples for H. pylori and a polymerase chain reaction was carried out to check for the presence or absence of cagA gene and the status of iceA genotypes. RESULTS: Among the 368 suspected patients to be infected with H. pylori by means of clinical features and endoscopic findings; 103 (28%) were positive using culture technique. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (p=0.0001). Furthermore, this study revealed that 100% of ulcer cases were infected with iceA1 with a statistically significant correlation (p=0.0001), while 94.6% of gastritis and 90.9% of normal were infected with iceA2 (p=0.0001). Moreover cagA+/iceA1 combined genotypes was statistically correlated with peptic ulcer (100%) but not cagA-/iceA1 (0%; p=0.0001). CONCLUSION: Certain H. pylori genotypes were more virulent than others. Multiple clinical implications based on these finding might be studied further. PMID- 17334465 TI - Enteroparasitic occurrence in stools from residents in Southwestern region of Saudi Arabia before and during Umrah season. AB - OBJECTIVE: Study of the prevalence of human gastro-intestinal parasitic infections among patients living in Makkah Al-Mukkarmah city before and during Umrah season. METHODS: One hundred eighty three stool samples were collected from patients living in Makkah, between the months of March and November 2005. Eighty were collected before the Umrah season began and 103 were collected during the Umrah season. Age, sex, and address were also recorded. Samples were preserved in 10% formol saline. They were examined using the direct smear technique and the formol ether concentration method. RESULTS: The results suggest a higher prevalence of intestinal parasitic infections (70.5%) among the patients under study. Entamoeba histolytica/E. dispar and Giardia lamblia were found to be the most common intestinal parasites among patients before and during Umrah. The infection rate was higher in the under 30 age group (74.8%) and in persons living away from the Holy Masjid (77.7%). The prevalence of intestinal parasitoses during Umrah (73.8%) was higher than that before Umrah (66.3%). CONCLUSION: The present study suggests that the group of people may underline the significant increase in the prevalence of intestinal parasitic infections during Umrah season. This highly significant increase of parasitic infection rate (p=0.018) was elicited when results were compared by one-way analysis of variance (ANOVA). The present data were discussed with previous studies. PMID- 17334466 TI - An evidence of high prevalence of Hepatitis C virus in Faisalabad, Pakistan. AB - OBJECTIVE: To see the prevalence of Hepatitis C virus (HCV) and its genotypes in general population of the locality and to evaluate the importance of reverse transcriptase-polymerase chain reaction (RT-PCR) test over HCV antibody test in early diagnosis of HCV infection. METHODS: The study took place at the National Institute for Biotechnology and Genetic Engineering (NIBGE) and we collected the samples from HCV screening camps organized by Allah Rakhi Trust Hospital Faisalabad and from blood donors visiting to Allied Hospital Faisalabad. Blood samples from 300 subjects (77% males and 23% females) with a mean average age of 32 +/- 20 years were randomly collected, and analyzed after separating the plasma by serological testing as well as molecular methods during the period from January 2004 to December 2004. Genotyping of HCV positive samples were performed by restriction fragment length polymorphism (RFLP) analysis of the PCR products. RESULTS: The results indicated that 48 (16%) cases were positive for anti-HCV antibody and 14 (4.7%) were on the borderline. Alanine aminotransferase (ALT) level indicated a wide range of activity from 5.0 U/L to 128 U/L. On the average, 79.4 U/L activity was found. By nested PCR, 84 (28%) samples were positive for HCV-RNA. The results of genotyping have indicated that 8 (9.5%) samples were of genotype-1 while only 2 (2.4%) samples were of HCV genotype-2. Hepatitis C virus genotype-3 was found to be major prevalent genotype as it was present in 68 (81%) samples. Six (7.1%) samples could not be identified by this method thus remained un-typed. CONCLUSION: Hepatitis C virus-RNA detection by molecular method was found to be more sensitive for early diagnosis of HCV infection and relatively higher incidence of HCV infection with genotype-3 was found in general population of the area. PMID- 17334467 TI - Acute disseminated encephalomyelitis in children. A descriptive study in Tehran, Iran. AB - OBJECTIVE: To determine the frequency, etiology (viral infection or vaccination), presenting signs and symptoms, response to therapy, complication and course of acute disseminated encephalomyelitis (ADEM) in our hospitals. METHODS: A 2-year retrospective, descriptive, chart review of children with final diagnosis of ADEM in 2 hospitals (Hazrat Rasool and Mofid in Tehran, Iran during 2000-2002) were carried out. The diagnosis is based upon clinical presentation, physical examination and ruling out of other disease (imaging, laboratories and so forth) of expert pediatric neurologists. Acute disseminated encephalomyelitis was documented in all cases by characteristics MRI changes included inflammation and demyelination in subcortical or periventricular regions. RESULTS: Acute disseminated encephalomyelitis were diagnosed in 15 patients. More than half of patients were between 9-14 years old. It was rare in 1-5 years old children. It had an abrupt onset, preceding infection/vaccination with no gender differences. Approximately 46.4% of cases had a recent upper respiratory tract illness. Varicella zoster virus infection, urinary tract infection, and mycoplasma pneumoniae were observed. Presentation signs included ataxia, decreased consciousness, fever plus nausea/vomiting, cranial nerve involvement, dysarthric speech, convulsion, hemiparesis, paresthesia, meningismus, and headache. We identified inflammation and demyelination in subcortical than periventricular lesions by magnetic resonance imaging. Prognosis was excellent with low mortality rate (6.6%). CONCLUSION: Acute disseminated encephalomyelitis is common in our children, possibly because of the high prevalence of causative infections. Due to advances in control of traditional exanthematous diseases such as measle, rubella and so forth, most cases of ADEM in this study followed non-specific upper respiratory infections. Differentiation of ADEM from a single episode of multiple sclerosis is difficult. Diagnosis of multiple sclerosis should be carried out if new symptoms and signs or imaging abnormalities appear, more than 3 months after the onset of clinical symptoms in ADEM cases. PMID- 17334468 TI - Contributing factors of preterm delivery in parturient in a University Hospital in Iran. AB - OBJECTIVE: Preterm labor is one of the common causes of prenatal morbidity and mortality. With considering the importance of preterm labor and lack of sufficient studies about the relationship between preterm labor and some factors such as cigarette smoking and opiate-using, the present study was designed. METHODS: We performed this descriptive-analytic study on 988 pregnant women referring to the Delivery Ward of Afzalipour Hospital, Kerman, Iran from February 2005 to September 2006. We analyzed the data using t-test and Chi-square test. RESULTS: From 988 subjects, 39.4% had preterm labor and 60.6% had term delivery. There was no significant difference between preterm and term groups in regard to their mean age (26.7 +/- 5.6 and 26.5 +/- 5.7 years), job, gravidity, educational level, abortion history, and periodontal or urinary infection (p>0.05). In preterm group, the rate of previous history of preterm labor (56%) and family history of preterm labor (88%) were significantly more in comparison to term delivery (p<0.1 and p<0.001). In women with a cigarette smoker husband, the rates of preterm labor was 44,6% and term labor was 55.4%, while in the case of both couples being cigarette smoker the rate of preterm labor was 69.2% and term labor was 31.9% (p<0.0001). In couples that were cigarette smoker and substance consumer, the rate of preterm was 77.4% and term labor was 22.6% (p<0.0001). CONCLUSION: The results of this study showed that women with personal and family history of preterm labor and women cigarette smokers and opiate-using should be considered as a major risk for preterm labor. PMID- 17334469 TI - Respiratory failure in organophosphate insecticide poisoning. AB - OBJECTIVE: Organophosphate compounds (OP) are usual insecticides and may poison human beings in a suicide attempt or accidental exposure. They inhibit activity of cholinesterase. Poisoning may be enough sever for intensive care support. In this paper, we study the prevalence and management of sever cases as well. METHODS: We studied patients with OP poisoning, from November 2002 to November 2005 in Sina Hospital, Tabriz, Iran, retrospectively and found patients who needed intensive care. During 4 years study, we documented 80 patients who were hospitalized due to OP poisoning and used drugs. Treatment with intravenous atropine and pralidoxime was started as soon as possible. We did not administer pralidoxim for 20 patients due to late admission (5 patients) and unavailability of the medicine (15 patients). RESULTS: Forty-five male and 35 female patients were enrolled in our study. The majority of the patients used OP for suicide attempt and 4 patients had accidental exposure. The mortality rate was 18% in patients who were treated with pralidoxim and patients without pralidoxim had a mortality rate of 21%. Ten patients were mechanically ventilated and the mortality rate was 50%. In patients without MV the mortality rate was 11.7%. The duration of intensive care stay was 7.1 +/- 2 days. CONCLUSION: Organophosphate compounds poisoning is a serious and lethal condition and needs early diagnosis and appropriate treatment. In patients with respiratory failure the mortality is very high; therefore we recommended early diagnosis, careful monitoring and appropriate management of complications in reducing the mortality rate. PMID- 17334470 TI - Quality assurance in an adult intensive care unit, Eastern region, Saudi Arabia. AB - OBJECTIVE: Quality assurance (QA) is an increasingly important element in the administrative management of Intensive Care Unit (ICU). This is not only to improve clinical practices and patient's outcome, but also helps in proper resource utilization. We introduced a comprehensive quality assurance program in ICU at King Abdulaziz National Guard Hospital, Alhasa, Saudi Arabia, based on the existing medical evidence. METHODS: We identified an already-validated set of quality indicators in intensive care and grouped them in categories of outcome measures (which reflect patient's subsequent health status) and process measures (related to patient-healthcare professional's interaction). Data collection forms were developed for nurses and physicians. Data were reported on monthly basis starting from January 2005, and the first 10 months data are presented. RESULTS: Three hundred eighty-seven patients were admitted during the study period. Approximately 56.9% had cardiac related diseases, 33.5% had medical ailments, and 9.6% had surgery related issues. There were 54.6% males and 45.4% females. Mean age of the patients was 58.4 +/- 18.3 years. The mean acute physiology and chronic health evaluation II (APACHE-II) score was 13.6 +/- 4.9. Outcome measures were either better or comparable to international data, while adherence to process measures was found to be excellent. Standardized mortality ratio for the duration of study was 0.24 with 95% confidence interval from 0.15-0.36. CONCLUSION: Implementation of QA program is practical in an ICU. Disseminating the quality monitoring information at national level can lead to a broad data base, which can identify the best performing ICUs, thus, leading to bench marking and creating risk adjusted models applicable to local population. PMID- 17334471 TI - Prevalence of and risk factors for peripheral arterial disease in Saudi Arabia. A pilot cross-sectional study. AB - OBJECTIVE: To determine the prevalence of and the risk factors for Peripheral arterial disease (PAD) in a primary health care setting in Saudi Arabia. METHODS: We conducted a prospective cross-sectional study of Saudi patients aged >or= 45 years, who attended the primary health care center at King Khalid University Hospital between February 2006 and March 2006. A pre-designed questionnaire was used for each patient. Peripheral arterial disease was diagnosed, if the Ankle Brachial index by Doppler were <0.90 and if the patient had signs or symptoms suggestively for PAD. Prevalence was estimated with 95% confidence intervals (CI), and multivariable logistics regression analyses were preformed to identify factors associated with PAD. RESULTS: A total of 471 patients were recruited. The mean age was 56 years and 32.3% were women. The prevalence of PAD was 11.7% (95% CI: 8.9-14.9%), and 92.7% of them were asymptomatic. Patients with PAD were slightly older than patients without PAD, suffered more often from diabetes, hypertension, lipid disorders, smoking, cerebrovascular event, and coronary artery disease. CONCLUSION: Prevalence of and risk factors for PAD in Saudi Arabia seem to be higher. A nationwide screening program is needed to confirm these results. PMID- 17334472 TI - Life style and nutrition and their impact on health of Saudi school students in Abha, Southwestern region of Saudi Arabia. AB - OBJECTIVE: To evaluate the life style and dietary habits of school students and the prevalence of some nutritional problems. METHODS: We conducted this study in Abha city during the scholastic year 2000. A two-stage random sample was used to select the students. The sample consisted of 767 male and female students in different grades of education. A designed questionnaire was used to collect data regarding life style practices and dietary habits. Weight, height, and body mass index were obtained. RESULTS: Diets were rich in carbohydrates, and deficient in fiber. Breakfast was a regular meal for 72% of primary school students compared to 49% of secondary school students. Milk was consumed daily by 51.5% of the sample; fast food consumption was low (2.0 +/- 1.7 times/month). Physical exercise was practiced significantly longer by males than by females; 8.6% and 5.8% of males in intermediate and secondary grades were smokers. Sleeping hours during school days were adequate (7.4 +/- 1.7 hours/day), but relatively higher (9.5 +/- 2.3) during vacation. Underweight (18.9%), obesity (15.9%), and overweight (11%) were prevalent. Overweight and obesity were significantly more prevailing among females of primary and secondary grades. CONCLUSION: Health education and physical education programs in the schools are recommended to promote healthy life styles and dietary habits. School feeding programs may be required to achieve some of these goals. PMID- 17334473 TI - Voice disorders in teachers. The role of family physicians. AB - OBJECTIVE: To look at the prevalence and impact of voice problems on teachers and assessing the teachers knowledge on vocal hygiene and habits, as well as which parameters mostly triggered the seeking of medical attention and how family doctors could intervene in this spectrum. METHODS: A survey that consists of 16 questions was used to look at the prevalence and impact of voice problems on teachers and to identify the associated risk factors at the American University of Beirut, Lebanon, during the year 2005. RESULTS: A considerable proportion (46%) perceived their voice as fair or worse, and 79% had never consulted a throat specialist. Voice disorders affected most of teachers particularly on their job. The mean number of vocal habits per person was estimated at 2.4 with smoking being the most common (38.7%). Two thirds of teachers were unaware of more than half the factors that can negatively affect their voice. Symptoms exceeding 6 months significantly increased the probability of consulting a physician by 2.5 folds. CONCLUSION: Family physicians can reduce the prevalence of vocal dysfunction in teachers through education and by pointing the various symptoms necessitating a specialist's early consultation especially when history of smoking is present. PMID- 17334474 TI - Noncompaction cardiomyopathy in the State of Qatar. AB - OBJECTIVE: To study the development of noncompaction of the ventricular myocardium (NCCM) in the state of Qatar and to highlight the prognostic parameters in those patients. METHODS: We conducted this study from 2000 to 2004 on patients who were referred to Hamad General Hospital with questionable echocardiographic features of cardiomyopathy with or without clinical manifestations of heart failure and were found to have NCCM. The diagnosis of NCCM was made according to echocardiographic criteria in 12 cases and those patients are followed up for 2-5 years. RESULTS: The mean age at diagnosis of NCCM was 6.5 years. Among them, 4 were males and 8 were females. Family history of NCCM was reported in 5 cases. Normal ejection fraction was detected in 5 patients; in this group pulsed-Tissue Doppler Imaging revealed evidence of subclinical systolic dysfunction in 4 cases. All patients showed variable degrees of diastolic dysfunction. Severely impaired ejection fraction was found in 3 cases. Progression to dilated cardiomyopathy occurred in 4 cases. Site of noncompaction included left ventricle apex in all cases, inferoposterior in 11 cases, and lateral wall in 11 cases while biventricular noncompaction was noted in 4 cases. Electrocardiogram findings included right bundle branch blocker (3) patients, left bundle branch blocker (2), left ventricular hypertrophy (6) and right ventricular hypertrophy in 3 cases. Atrial tachyarrhythmias developed in 4 cases. Wolff-Parkinson-White syndrome was detected in one patient. Associated congenital anomalies included ventricular septal defect, pulmonary stenosis, aortic coarctation, and Ebstein anomaly. The overall mortality rate was 25%. CONCLUSION: Noncompaction cardiomyopathy is so rare to be easily missed. The prognosis is poor in symptomatic cases; however, detection of subclinical systolic dysfunction is needed. PMID- 17334475 TI - Consequences of radiotherapy on nutritional status, dietary intake, serum zinc and copper levels in patients with gastrointestinal tract and head and neck cancer. AB - OBJECTIVE: Malnutrition occurs frequently in cancer patients and is multifactorial and can lead to negative outcomes. So we studied the effect of radiotherapy on nutritional status, weight changes, dietary intake, serum zinc and copper levels. METHODS: During the period of October to March 2005, 45 cancer patients who referred to the Radiotherapy Center, Imam Khomeini Hospital, Iran were recruited. We assessed the nutritional status of patients using Patient Generated Subjective Global Assessment (PG-SGA) questionnaire. Patients on the basis of location of radiotherapy classified to mediastinum, head and neck and pelvic groups. Changes in dietary intake (using 24-hour recall method) and body weight were evaluated prior to and during radiotherapy. At the onset and the end of radiotherapy, serum levels of zinc, copper and albumin were determined. RESULTS: After treatment malnutrition increased significantly in all patients (p=0.01) and in head and neck (p=0.007) and pelvic groups (p=0.04). The decreased body weight of patients was significant in the head and neck (p=0.02), and pelvic groups (p=0.005). The mean daily energy and protein intake of head and neck and pelvic groups decreased during radiotherapy while energy intake increased significantly in mediastinum group (p=0.01). After treatment, significant decreases also observed in mean serum zinc, copper and albumin levels (p<0.05). CONCLUSION: Because of the negative effect of radiotherapy on oral feeding, nutritional assessment and intervention should be an integral part of treatment. Also, it would be worthwhile studying the effect of zinc supplementation on dietary intake and nutritional status of patients. PMID- 17334476 TI - Prevalence of vitamin D deficiency rickets in adolescent school girls in Western region, Saudi Arabia. AB - OBJECTIVE: To determine the prevalence of vitamin D deficiency rickets among female adolescents and assess its relation to calcium intake and sun exposure. METHODS: Four hundred and thirty-three school girls between 12-15 years old were selected randomly from different schools in Jeddah, between October 200--February 2004. We identified symptoms of rickets and determined the dietary habits and sun exposure habits, and laboratory investigations were also carried out. RESULTS: It was found that, out of 433 cases, 350 (81%) had low vitamin D levels. Approximately 40% had very low levels of vitamin D and 61% were asymptomatic. Most of the symptoms were non specific. There was a positive correlation between low calcium in the diet and less sun exposure to low levels of vitamin D. Approximately 96% had normal serum phosphate, 89% had normal serum calcium, and 40% had normal serum alkaline phosphatase levels. CONCLUSION: Vitamin D deficiency is common among adolescent females in Jeddah, Saudi Arabia. Cases are missed due to lack of symptoms in most cases and normal bone chemistry. Serum vitamin D level should be carried out in suspected cases. Health and nutritional education should be encouraged in schools. Focusing on the importance of adequate milk intake and sun exposure should be given a priority in any health education program. PMID- 17334477 TI - Comparison of the effect of gonadotropin-releasing hormone analog (Diphereline) and Cabergoline (Dostinex) treatment on uterine myoma regression. AB - OBJECTIVE: To investigate the effect of cabergoline (Dostinex, a dopamine agonist) on the myoma growth compared to Diphereline (a gonadotropin-releasing hormone agonist). METHODS: This study took place in the Department of Obstetrics and Gynecology of Tabriz University of Medical Sciences, Tabriz, Iran from July 2004 to December 2005. Fifty women with uterine myoma, who met the criteria of the study thoroughly, were randomly allocated into 2 equal groups to take either Diphereline or Cabergoline. The first Group took 3.75 mg of Diphereline 4 times every 28 days and the second group took 0.5 mg of Cabergoline once a week for 6 weeks. RESULTS: The Cabergoline was well tolerated and fewer adverse effects were noted. The tumor regressed significantly and volume reduction rate of individual tumor nodule varied from 46-53%. The gonadotropin releasing hormone agonist group all responded to the treatment, and volume reduction rate of the individual tumor nodule varied from 21-97%. The extent of tumor shrinkage was positively correlated to the number of nodules (p=0.881, p<0.005 and 0.701, p<0.005). CONCLUSION: In light of therapeutic efficacy and few adverse effects, the dopamine agonists may hold promise as novel treatment modalities for leiomyoma. Further studies are warranted to determine the optimal strategy for the treatment of leiomyoma through these agents. PMID- 17334478 TI - Treatment of spontaneous coronary artery dissection with drug-eluting stents. AB - Spontaneous coronary artery dissection SCAD is a rare condition which may result in sudden coronary occlusion, acute myocardial infarction and sudden cardiac death. The prognosis of spontaneous coronary artery dissection is uncertain and optimal treatment is unknown. We describe a case of SCAD in a 29-year-old male with acute inferior wall myocardial infarction MI and post-MI angina that was treated with drug-eluting stents. PMID- 17334479 TI - Radiological evidence of double inferior vena cava in a young adult male. AB - The development of the inferior vena cava IVC is a complex process comprising the formation and regression of some anastomoses, so various anomalies may occur during embryogenesis. These variations can increase the difficulty of aneurysm resection as well as the risk of venous injury and subsequent excessive bleeding during retroperitoneal and thoracic surgical interventions. Here, we report a patient with double inferior vena cava by radiographically during his investigation for the etiology of pancytopenia. PMID- 17334480 TI - Schimke immuno-osseous dysplasia. AB - Schimke immuno-osseous dysplasia SIOD is a rare autosomal recessive disorder characterized by steroid resistant nephrotic syndrome, immune deficiency, and osseous dysplasia. SW/SNF2 related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1 SMARCAL 1 is the gene responsible for SIOD but the underlying pathophysiologic mechanism is unclear, therefore, there is limited therapeutic options. To our best knowledge, less then 50 cases of SIOD have been published and we report 2 more cases with typical clinical and laboratory features from South of Iran. It is emphasized that this disorder should be considered in children with steroid resistant nephrotic syndrome and bone dysplasia. PMID- 17334481 TI - Aggressive rhabdomyosarcoma of the vulva in a young Sudanese woman. AB - A 22-year-old para 2, female presented with a 2-month history of a progressively vulvar mass. Clinically, her general condition was poor. She had bilateral inguinal lymphadenopathy. Local examination revealed a large deeply infiltrating vulvar mass. Pathological evaluation revealed pleomorphic rhabdomyosarcoma. PMID- 17334482 TI - Coexisting malignant lymphoma of the duodenum and adenocarcinoma of the colon. AB - Synchronous malignant mucosa associated lymphoid tissue MALT-lymphoma of the small bowel and adenocarcinoma of the colon in the same patient is a scarce rarity. Only few cases have been reported so far. Thus, it might be of interest to report such a case of coexisting malignant MALT-lymphoma of the duodenum and adenocarcinoma of the large bowel. PMID- 17334483 TI - A giant testicular teratoma. AB - We report a giant testicular in a 36-year-old farmer man, of 18-month duration admitted to the Surgical Department Erbil Teaching Hospital, Iraq. The tumor was invading the penis and lower part of abdominal wall including bilateral groin lymph nodes. Histological examination revealed mature and immature teratoma. Further investigations showed no evidence of any metastatic lesions apart from a solitary pulmonary nodule on the right side of the chest which proved by ultra sonic guide fine needle aspiration biopsy. Radical excisions of the tumor including the shaft of the penis, combined with bilateral block dissection of the inguinal nodes and resection of the lower anterior abdominal wall was performed. Six weeks later after a course of chemotherapy and radiotherapy, the patient underwent resection of metastatic lung lesion. PMID- 17334484 TI - Fracture and aspiration of metallic tracheostomy tube. PMID- 17334485 TI - Diagnosis and management of pediatric cardiac hydatid cyst. PMID- 17334486 TI - Toxic epidermal necrolysis due to procaine penicillin. PMID- 17334487 TI - Relationship of early hypertensive retinopathy to inflammation markers and microalbuminuria in hypertensive patients with regulated blood pressure. PMID- 17334488 TI - Diabetic scenario in Arabs. PMID- 17334489 TI - Effect of Helicobacter pylori eradication on short-term control of glycemia in patients with type 2 diabetes mellitus. PMID- 17334490 TI - Arabian incense exposure among Qatari asthmatic children. A possible risk factor. PMID- 17334491 TI - Maternal serum ferritin and hemoglobin values in patients with gestational diabetes mellitus. PMID- 17334492 TI - Clubbing in a patient with liver disease. PMID- 17334493 TI - Retrospective or descriptive study. PMID- 17334494 TI - Diagnosis of vasculitis. PMID- 17334495 TI - The clinical significance of circulating tissue factor in prostate cancer. PMID- 17334496 TI - Prevention of transient endothelial dysfunction in acute exercise: a friendly fire? PMID- 17334497 TI - Signaling in endothelial cells: 10 years Department of Vascular Biology and Thrombosis Research at the Medical University Vienna. PMID- 17334498 TI - uPAR-uPA-PAI-1 interactions and signaling: a vascular biologist's view. AB - The urokinase-type plasminogen activator (uPA), its inhibitor PAI-1 and its cellular receptor (uPAR), play a pivotal role in pericellular proteolysis. In addition, through their interactions with extracellular matrix proteins as well as with transmembrane receptors and other links to the intracellular signaling machinery, they modulate cell migration, cell-matrix interactions and signaling pathways. A large body of experimental evidence from in-vitro and in-vivo data as well as from the clinics indicates an important role of the uPA-uPAR-PAI-1 systems in cancer. In addition to their role in tumor cell biology, the uPA-uPAR PAI-1 systems are also important for vascular biology by modulating angiogenesis and by altering migration of smooth muscle cells and fibrin deposition in atherosclerosis and restenosis. This review will focus on the general mechanism of uPAR/uPA/PAI-1 interactions and signaling and the possible relevance of this system in vascular biology. PMID- 17334499 TI - Protein C inhibitor, a serpin with functions in- and outside vascular biology. AB - Human protein C inhibitor (PCI), a serpin-type protease inhibitor originally described as an inhibitor of activated protein C, has broad protease reactivity. In addition to its activities within the blood clotting and fibrinolytic cascades, it seems to participate in several biological processes including reproduction and tumor growth. This review summarizes the current understanding of PCI function, regulation, and potential biological role. PMID- 17334500 TI - Inflammatory profile of oxidized phospholipids. AB - Lipid oxidation products and in particular oxidized phospholipids (OxPL) are increasingly recognized as inducers of chronic inflammation characteristic of atherosclerosis. OxPL stimulate production of chemokines and adhesion of monocytes to endothelial cells. However, accumulating data suggest that, in addition to the proatherogenic and proinflammatory effects, OxPL can stimulate antiinflammatory and tissue-protective mechanisms. Thus, depending on the biological situation, OxPL can either stimulate or inhibit inflammation. In this review, the inflammatory properties of OxPL are discussed together with the underlying receptor, signalling and transcriptional mechanisms. PMID- 17334502 TI - Resolution of inflammation: intracellular feedback loops in the endothelium. AB - Timely termination of the inflammatory reaction is equally important as its elicitation, since a persistent or exaggerated response may lead to detrimental effects in the affected tissues and organs. Therefore, and in accordance with the complex and highly coordinated activation phase, negative regulatory mechanisms have evolved which function on multiple levels to ensure the appropriate termination of the inflammatory response. This review will focus on the mechanisms that are operative in endothelial cells to shut down the activity of specific signaling pathways and transcription factors that have been activated in response to pro-inflammatory mediators, and provide evidence that the stage for resolution is set already early in the activation phase of the inflammatory response. The elucidation of these feedback mechanisms is of importance for the understanding of acute versus chronic inflammation, and for novel strategies for therapeutic intervention. PMID- 17334503 TI - Ubiquitylation within signaling pathways in- and outside of inflammation. AB - Ubiquitin is a highly conserved 76-amino-acid peptide that becomes covalently attached to lysine residues of target proteins. Since ubiquitin itself contains seven lysine residues, ubiquitin molecules can generate different types of polyubiquitin chains. Lys48-linked polyubiquitylation is well-known as posttranslational tag for targeting proteins for degradation by the 26S proteasome. Recent studies have revealed several new functions of ubiquitin, e.g. activation of protein kinases, control of gene transcription, DNA repair and replication, intracellular trafficking and virus budding. These functions are mainly mediated by Lys63 polyubiquitin chains or attachment of a single ubiquitin molecule to one or several lysine residues within the target protein. Importantly, protein ubiquitylation exhibits inducibility, reversibilty and recognition by specialized ubiquitin-binding domains, features similar to protein phosphorylation. In this review we comprehensively describe regulations of protein ubiquitylation and their impact on distinct signaling pathways. PMID- 17334501 TI - Signal transduction induced in endothelial cells by growth factor receptors involved in angiogenesis. AB - New vessel formation during development and in the adult is triggered by concerted signals of largely endothelial-specific receptors for ligands of the VEGF, angiopoietin and ephrin families. The signals and genes induced by these receptors operate in the context of additional signals transduced by non endothelial specific growth factor receptors, inflammatory cytokine receptors as well as adhesion molecules. We summarize here available data on characteristic signaling of the VEGF receptor-2 and the current state of knowledge regarding the additional different receptor tyrosine kinases of the VEGF, Tie and Ephrin receptor families. Furthermore, the potential cross-talk with signals induced by other growth factors and inflammatory cytokines as well as the modulation by VE cadherin is discussed. PMID- 17334504 TI - Fluorescent proteins and fluorescence resonance energy transfer (FRET) as tools in signaling research. AB - The advent of fluorescent proteins has revolutionized signaling research, shifting focus from biochemical assays to analysis of live cells, organized tissues and even entire organisms. Modern applications of fluorescent proteins go beyond their use as specific markers of cells or tissues, allowing the researcher to visualize intracellular translocations as well as biochemical reactions. In this mini-review, we summarize the properties of a variety of fluorescent proteins, their detection using fluorescence microscopy and flow analysis, as well as their basic and more advanced applications, including fluorescence resonance energy transfer (FRET) to study signaling dynamics. PMID- 17334505 TI - Thienopyridines in cardiovascular disease: focus on clopidogrel resistance. AB - Platelets play an important role in atherothrombotic disease, as well as in the pathogenesis of atherosclerosis and in complications. Antiplatelet therapy with clopidogrel represents at present an important treatment of coronary artery disease (CAD), especially in and after acute coronary syndromes (ACS), and after coronary interventions when stents are used. Clopidogrel is a potent and specific inhibitor of platelet ADP receptor (P2Y(12) receptor) with high antithrombotic activity. Emerging data suggest that a significant percentage of individuals treated with clopidogrel do not receive the expected therapeutic benefit because of a decreased responsiveness of their platelets, which is caused by several extrinsic and/or intrinsic mechanisms. As long as clopidogrel is the "gold standard" in combination with aspirin in the treatment of patients undergoing percutaneous coronary intervention and stent implantation, the overall challenge is to develop a fast "point-of-care" assay to detect clopidogrel resistance early and to enable alternative antithrombotic strategies in non-responders or low responders. This test should be easily performed (bedside) and reproducible, with a standardized definition of response, which is known to correlate with clinical outcomes. Unfortunately, such a test does not exist at present. As an alternative, new ADP receptor antagonists with better bioavailability and improved pharmacokinetics, e.g. intestinal reabsorption as an active drug or 1:1 conversion into an active metabolite thus reducing individual variations, are in development and have already found their way into clinical use in phase-3 trials. Prasugrel is one of the incoming new drugs with high expectations, but other agents might follow in the near future. PMID- 17334506 TI - Expression of the serine protease inhibitor neuroserpin in cells of the human myeloid lineage. AB - Myeloid progenitors in the bone marrow differentiate into most of the major cell types of the immune system, including macrophages and dendritic cells. These cells play important roles in both innate and adaptive immunity. They express a number of proteases and protease inhibitors including members of the serine proteinase inhibitor or serpin superfamily. In this study we report the differential expression of neuroserpin in cells of the human myeloid lineage. Neuroserpin was highly expressed and secreted following the differentiation of monocytes to macrophages and dendritic cells. Activation of dendritic cells with lipopolysaccharide resulted in increased neuroserpin mRNA levels but no neuroserpin secretion. Confocal immunofluorescence microscopy showed neuroserpin was differentially localised in human myeloid cells. In macrophages and dendritic cells it was concentrated in vesicles located in close proximity to the plasma membrane. The majority of activated dendritic cells also exhibited an intracellular focal concentration of neuroserpin which co-localised with the lysosomal/late endosomal marker LAMP-1. As neuroserpin inhibits tissue plasminogen activator, a comparative analysis of tPA and plasminogen activator inhibitor-1 (PAI-1) expression was undertaken. This analysis revealed differential expression of PAI-1 and neuroserpin suggesting they may have different functions in human immune cells. PMID- 17334507 TI - Resolution of venous thrombosis using a novel oral small-molecule inhibitor of P selectin (PSI-697) without anticoagulation. AB - P-selectin inhibition has been shown to decrease thrombogenesis in multiple animal species. In this study, we show that a novel oral small-molecule inhibitor of P-selectin, PSI-697, promotes thrombus resolution and decreases inflammation in a baboon model of venous thrombosis. Experimental groups consisted of the following: 1) primates receiving a single oral dose of PSI-697 (30 mg/kg) daily starting three days pre-iliac vein balloon occlusion, and continued for six days; 2) primates receiving a single treatment dose of a low-molecular-weight-heparin (LMWH) (1.5 mg/kg) daily starting one day pre-iliac balloon occlusion, and continued for six days; and 3) primates receiving a single oral dose of a vehicle control daily starting three days pre-iliac vein balloon occlusion, and continued for six days. Animals receiving PSI-697, although thrombosed after balloon deflation, demonstrated greater than 80% vein lumen opening over time, with no opening (0%) for vehicle control (p < 0.01). LMWH opening evident after balloon deflation slightly deteriorated over time compared to PSI-697. PSI-697 therapy also significantly decreased vein wall inflammation determined by magnetic resonance venography (MRV). Importantly, this beneficial opening occurred without measured anticoagulation. Animals receiving PSI-697 demonstrated significantly increased plasma D-dimer levels versus LMWH and control animals six hours post thrombus induction (p < 0.01). This study is the first to demonstrate the effectiveness of oral P-selectin inhibition to modify venous thrombogenesis, increase vein lumen opening, and decrease inflammation in a large animal model. PMID- 17334508 TI - Self-management of oral anticoagulation in the elderly: rationale, design, baselines and oral anticoagulation control after one year of follow-up. A randomized controlled trial. AB - Self-management is safe and reliable in patients with long-term oral anticoagulation (OAC). However, no study has yet assessed the safety and efficacy of OAC self-management in elderly patients with major thromboembolic and haemorrhagic complications as primary outcomes. In this multi-centre, open, randomised controlled trial, patients aged 60 years or more were randomised into the self-management group (SMG) (N = 99) or routine care group (RCG) (N = 96). We describe the rationale, design, baseline characteristics and interim analyses of oral anticoagulation control quality within the first year of follow-up. The medians of the squared international normalised ratio (INR) value deviations after six and 12 months were significantly lower in the SMG with medians of 0.16 and 0.16 compared to the RCG with medians of 0.25 and 0.25. The percentage of time within target range and the percentage of INR measurements within target range were significantly higher in the SMG versus the RCG within the first six months (medians 71% vs. 58% and 69% vs. 57%), and during the second six months of the study (75% vs. 67% and 72% vs. 57%). The numbers of all thromboembolic events requiring hospitalisation, major bleeding events, and deaths were similar in both groups. These preliminary results suggest that self-management of oral anticoagulation is safe and feasible for elderly patients willing to participate in a structured training programme. PMID- 17334509 TI - Platelet activation via PAR4 is involved in the initiation of thrombin generation and in clot elasticity development. AB - Thrombin is a pivotal enzyme formed in the coagulation cascade and an important and potent platelet activator. The two protease-activated thrombin receptors on human platelets are denoted PAR1 and PAR4. The physiological relevance of PAR4 is still unclear, as both aggregation and secretion can be accomplished by PAR1 activation alone. In the present study we have investigated the role of PARs in platelet activation, blood coagulation, clot elasticity and fibrinolysis. Flow cytometry, free oscillation rheometry and thrombin generation measurements were used to analyze blood or platelet-rich plasma from healthy individuals. Maximum PAR1 activation with the peptide SFLLRN gave fewer fibrinogen-binding platelets with lower mean fluorescent intensity than maximum PAR4 activation with AYPGKF. Inhibition of any of the receptors prolonged clotting times. However, PAR1 is more important for fibrinolysis; inhibition of this receptor prolonged all the steps in the fibrinolytic process. Clot elasticity decreased significantly when the PAR4 receptor was inhibited. In the thrombin generation measurements, PAR4 inhibition delayed the thrombin generation start and peak, but did not affect the total amount of thrombin generated. PAR1 inhibition had no significant impact on thrombin generation. We found that PAR4 is most likely activated by low concentrations of thrombin during the initial phase of thrombin generation and is of importance to the clotting time. Furthermore, we suggest that the PAR4 receptor may have a physiological role in the stabilisation of the coagulum. PMID- 17334510 TI - Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. AB - Platelet microparticles (PMPs) are small vesicles released from blood platelets upon activation. The procoagulant activity of PMPs has been previously mainly characterized by their ability to bind coagulation factors VIII and Va in reconstructed systems. It can be supposed that PMPs can contribute to the development of thrombotic complications in the pathologic states associated with the increase of their blood concentration. In this study, we compared procoagulant properties of calcium ionophore A23187-activated platelets and PMPs using several in-vitro models of hemostasis. Surface densities of phosphatidylserine, CD61, CD62P and factor X bound per surface area unit were determined by flow cytometry. They were 2.7-, 8.4-, 4.3-, and 13-fold higher for PMPs than for activated platelets, respectively. Spatial clot growth rate (V(clot)) in the reaction-diffusion experimental model and endogenous thrombin potential (ETP) were determined in plasma, which was depleted of phospholipid cell surfaces by ultra-centrifugation and supplemented with activated platelets or PMPs at different concentrations. Both V(clot) and ETP rapidly increased with the increase of PMP or platelet concentration until saturation was reached. The plateau values of V(clot) and ETP for activated platelets and PMPs were similar. In both assays, the procoagulant activity of one PMP was almost equal to that of one activated platelet despite at least two-orders-of-magnitude difference in their surface areas. This suggests that the PMP surface is approximately 50- to 100-fold more procoagulant than the surface of activated platelets. PMID- 17334511 TI - Glycoprotein Ibalpha inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques. AB - Anti-platelet drugs are used to prevent intra-arterial thrombus formation after rupture of atherosclerotic plaques. Until now, the inhibitory effect of present and future anti-platelet drugs such as aspirin, ADP receptor P2Y(1)/P2Y(12) antagonists and glycoprotein (GP) Ibalpha inhibitors on the interaction of platelets with human plaques is not known. To study those effects we obtained human atherosclerotic plaques by surgical endarterectomy. Plaques induced maximal platelet aggregation in hirudinized platelet-rich plasma (PRP) and blood that was effectively inhibited by aspirin, the P2Y(1) antagonist MRS2179 and the P2Y(12) antagonist AR-C69931MX, but not by GPIbalpha blockade with the mAB 6B4. Inhibition of platelet aggregation by MRS2179 was 74 +/- 37% and 68 +/- 20%, by AR-C69931MX 94 +/- 7% and 80 +/- 6%, and by aspirin 88 +/- 19% and 64 +/- 28%, in PRP and blood, respectively (mean +/- SD; n = 6-12 with plaques from 6 patients). The combination of both ADP receptor antagonists completely inhibited plaque induced platelet aggregation in hirudinized PRP and blood. Under arterial flow conditions (1,500s(-1)), blockade of platelet GPIbalpha resulted in a strong decrease of plaque-stimulated platelet adhesion/aggregate formation of 77 +/- 5% (mean +/- SD; n = 4). Furthermore, MRS2179, AR-C69931MX and their combination reduced plaque-dependent platelet aggregate formation by 35 +/- 14%, 32 +/- 13% and 58 +/- 12% (mean +/- SD; n = 5), respectively. Aspirin was without significant effect. In conclusion, a GPIbalpha-blocking antibody, as well as P2Y(1) and P2Y(12) receptor antagonists, alone or in combination, reduce in contrast to aspirin human plaque-induced platelet thrombus formation under arterial flow. Although these new anti-platelet agents inhibit platelet thrombus formation after plaque rupture, more efficient platelet blockers are required. PMID- 17334512 TI - Prevention by NCX 4016, a nitric oxide-donating aspirin, but not by aspirin, of the acute endothelial dysfunction induced by exercise in patients with intermittent claudication. AB - Ischemia/reperfusion damage evokes systemic inflammation and endothelial dysfunction in patients with intermittent claudication. We compared the effects of aspirin with those of a nitric oxide-donating aspirin in preventing the acute, systemic endothelial dysfunction provoked by exercise-induced ischemia of the lower limbs in patients with intermittent claudication. In a prospective, randomized, single-blind, parallel-groups trial among 44 patients with intermittent claudication we compared four weeks of aspirin (100 mg o.d.) with NCX 4016 (800 mg b.i.d.). Primary end point was the exercise-induced changes in brachial flow-mediated vasodilation (FMD) at day 28; secondary end points were effort-induced changes of markers of neutrophil (plasma elastase) and endothelial (soluble VCAM-1) activation. Baseline FMD was comparable in the two groups, both on day 1 (pre-treatment: aspirin = 3.1 +/- 0.5%, nitroaspirin = 3.9 +/- 0.7%, p = NS), and on day 28 (aspirin = 3.4 +/- 0.7%, NCX 4016 = 3.2 +/- 0.6%, p = NS). Maximal treadmill exercise induced an acute worsening of FMD in both groups at baseline (aspirin = -1.15%, nitroaspirin = -1.76%); after four weeks treatment, the impairment of FMD induced by exercise was still present in the aspirintreated group (-1.46%) while it was abolished in the NCX 4016-treated group (+0.79%, p = 0.038 vs. aspirin). Similarly, exercise induced an increase of plasma elastase and of sVCAM-1 which were not affected by aspirin while they were suppressed by NCX 4016. Maximal treadmill exercise induces a systemic arterial endothelial dysfunction in patients with intermittent claudication. A nitric oxide-donating aspirin, but not aspirin, prevents effort-induced endothelial dysfunction. PMID- 17334513 TI - The -11377 C>G promoter variant of the adiponectin gene, prevalence of coronary atherosclerosis, and incidence of vascular events in men. AB - No prospective data demonstrating an association between the -11377 C > G adiponectin gene promoter variant and cardiovascular risk are available. We therefore prospectively evaluated the cardiovascular risk associated with adiponectin gene single nucleotide polymorphisms (SNPs) including SNP -11377 in a consecutive series of men undergoing coronary angiography. We recorded vascular events over four years in 402 men undergoing coronary angiography for the evaluation of coronary artery disease. No significant associations of SNPs +276 G > T and +45 T > G with serum adiponectin, with significant coronary stenoses >50%, or with vascular events were observed. However, for SNP -11377 C > G, serum adiponectin levels significantly decreased (p(trend) = 0.003), and the prevalence of significant coronary stenoses significantly increased from the CC over the GC to the GG genotype (p(trend) = 0.004). Prospectively, the risk of vascular events significantly increased from the CC over the CG to the GG genotype of this SNP (adjusted hazard ratios 1.555 [0.957 - 2.525] and 2.309 [1.067 - 4.998], respectively; p(trend) = 0.014). The -11377 C > G adiponectin gene promoter variant is i) associated with decreased serum adiponectin levels, ii) correlated with the presence of coronary atherosclerosis and iii) significantly predictive of vascular events among men undergoing coronary angiography. PMID- 17334514 TI - Factor XIII Val34Leu variant protects against coronary artery disease. A meta analysis. AB - Several studies suggested that Val34Leu variant of factor XIII (FXIII) might have a protective effect against coronary artery disease (CAD), but studies not supporting these findings have also been published. The authors performed a meta analysis of 16 studies on 5,346 cases and 7,053 controls that investigated the association between Val34Leu polymorphism and CAD defined as history of myocardial infarction or significant stenosis on a coronary artery assessed by coronary angiography. Because of the heterogeneity of the study-specific results, the pooled effect estimates were calculated by a random-effects empirical Bayes model. The combined odds ratios for CAD were 0.82 (95% confidence interval [95% CI] 0.73, 0.94) for the heterozygotes of the FXIIIVal34Leu variant, 0.89 (95% CI 0.69, 1.13) for the homozygotes, and 0.81 (95% CI 0.70, 0.92) for the heterozygotes and homozygotes combined. The results were essentially the same when only myocardial infarction was considered as outcome. The beneficial effect of the polymorphism might be smaller than the effect estimates obtained in this meta-analysis, because the analysis raised the possibility of publication bias. Data published in the literature suggest that gene-gene and gene-environmental interactions might significantly influence the protective effect of FXIII-A Val34Leu polymorphism. PMID- 17334515 TI - Plasma tissue factor antigen in localized prostate cancer: distribution, clinical significance and correlation with haemostatic activation markers. AB - Tissue factor (TF) is involved in cancer growth and metastasis, and haemostatic abnormalities are found in most patients with advanced malignancies, including prostate cancer (PC). Because anti-haemostatic agents are increasingly screened for their potential to prolong survival in tumor patients, a detailed characterization of haemostatic markers in selected cancer subtypes and clinical stages is warranted. In this study, we measured preoperative plasma TF antigen in a large cohort of patients with localized PC and correlated its levels with markers of coagulation and platelet activation, prostate-specific antigen (PSA), and histopathological findings to explore its potential as a prognostic marker in this tumor entity. Out of 140 patients, 19% and 23% had plasma TF antigen levels of <40 pg/ml (low-TF) and >200 pg/ml (high-TF), respectively, which was substantially higher than in 42 healthy male controls. Patients also had low grade systemic coagulation activation as evidenced by elevated D-dimer, F1 + 2, and PAP plasma levels. Furthermore, similar to sP-selectin and sCD40L antigen, flow cytometric analysis of platelet-derived microparticles in plasma revealed significantly increased numbers in high-TF as compared to low-TF patients and controls. Whereas elevated D-dimer was associated with larger and less differentiated tumors, preoperative plasma TF antigen levels (median [IQR]) were higher in patients with (161 pg/ml [100-236]) than in those without recurrent PC (105 pg/ml [52-182]), as indicated by a serum PSA of >0.1 ng/ml during ambulatory follow-up. In patients with localized PC, preoperative plasma TF antigen levels correlate with platelet activation in vivo and may indicate an increased risk for recurrent disease. PMID- 17334516 TI - Prevention and treatment of experimental thrombosis in rabbits with rivaroxaban (BAY 597939)--an oral, direct factor Xa inhibitor. AB - Current anticoagulant therapies for the prevention and treatment of thromboembolic disorders have many drawbacks: vitamin K antagonists interact with food and drugs and require frequent laboratory monitoring, and heparins require parenteral administration. Oral rivaroxaban (BAY 597939) is a new, highly selective and potent direct factor-Xa (FXa) inhibitor with a predictable pharmacodynamic and pharmacokinetic profile and could therefore be an attractive antithrombotic drug. It was the objective of this study to investigate the antithrombotic efficacy of oral rivaroxaban in two rabbit models of experimental venous thrombosis. In the venous stasis (prevention) model, animals were randomized to receive oral rivaroxaban 0.3, 1.0, 3.0 or 10.0 mg/kg or vehicle control. Thrombosis was induced by jugular vein stasis and injection of thromboplastin into the ear vein. In the venous thrombosis (treatment) model, intravenous (1.0 and 3.0 mg/kg) and oral (3.0 mg/kg) rivaroxaban was compared with intravenous nadroparin (40 U bolus and 20 U/h), fondaparinux (42 microg/kg) and vehicle control. Thrombus growth was assessed by measuring the accretion of radiolabelled fibrinogen into preformed clots in the jugular veins. Bleeding was assessed using an ear bleeding model. In the prevention model, rivaroxaban reduced thrombus formation dose-dependently (calculated ED(50) 1.3 mg/kg). In the treatment model, oral rivaroxaban (3.0 mg/kg) reduced thrombus growth to a similar extent to intravenous rivaroxaban (1.0 mg/kg), nadroparin and fondaparinux. Oral rivaroxaban did not prolong bleeding time. In conclusion, the orally available selective, direct FXa inhibitor rivaroxaban is effective in the prevention and treatment of venous thrombosis in two well-established models of experimental thrombosis. PMID- 17334517 TI - Interaction of an annexin V homodimer (Diannexin) with phosphatidylserine on cell surfaces and consequent antithrombotic activity. AB - Annexin V (AV), a protein with anticoagulant activity, exerts antithrombotic activity by binding to phosphatidylserine (PS), inhibiting activation of serine proteases important in blood coagulation. The potential use of this protein as an anticoagulant is limited as it rapidly passes from the blood into the kidneys due to its relatively small size (36 kDa). We used recombinant DNA technology to produce a homodimer of human AV (DAV, 73 kDa), which exceeds the renal filtration threshold, and has a 6.5-hour half-life in the rat circulation. Human red blood cells with externalized PS were used to show that DAV had a higher affinity for PS-exposing cells than AV. DAV labeling sensitively identifies PS-exposing cells, was found to be a potent inhibitor of the activity of the prothombinase complexes and inhibits the ability of secretory phospholipaseA(2) to hydrolyze phospholipids of PS-exposing cells, reducing the formation of mediators of blood coagulation and reperfusion injury. DAV exerts dose-dependent antithrombotic activity in rat veins. This combination of activities suggests that DAV is a valuable probe to measure PS exposure and may be efficacious as a novel drug in a wide range of clinical situations. PMID- 17334518 TI - Potent arterial antithrombotic effect of direct factor-Xa inhibition with ZK 807834 administered to coronary artery disease patients. AB - It was the objective of this study to evaluate the anti-thrombotic potency of direct factor-Xa inhibition with ZK-807834 in stable coronary patients, using an ex-vivo model of arterial thrombus formation. Tissue factor pathway is important in atherothrombosis. Direct factor-Xa blockade may more potently reduce thrombosis and prevent coronary events. Badimon Perfusion Chamber 5-minute quantitative studies have shown 40-55% arterial thrombus reduction with abciximab, 23% with clopidogrel, but none with heparin. Coronary patients (n = 18, 59 +/- 9 years, 55% males) were blindly randomized to four groups receiving 24-hour infusion of a low, medium or high dose of direct factor- Xa inhibitor ZK 807834, or placebo. Arterial thrombus formation was measured in Badimon Chamber at baseline, end-of-infusion [EoI], and four hours and eight hours after EoI, and factor-X activity, prothrombin time [PT] ratio and plasma drug levels were measured simultaneously. For the low-, medium- and high-dose ZK-807834 groups, mean percent-reduction in thrombus size from baseline to EoI were 29%, 34% and 68%, respectively (p < 0.001), and at 8-h post EoI were 11%, 19% and 27%, respectively (p < 0.01). Mean PT-ratio prolongation showed a strong linear relationship (Pearson's r = 0.93) with ZK-807834 plasma concentration. Mean percent-reduction in factor-X activity from baseline was 13%, 42% and 58%, respectively. Placebo had no effect on thrombus size or factor-X activity. In conclusion, direct factor-Xa inhibition with ZK-807834 markedly reduces ex-vivo arterial thrombus formation and factor-X activity in a dose-dependent manner. Plasma levels of ZK-807834 show a strong linear correlation with PT ratio. This direct factor-Xa inhibitor may reduce the need for additional potent glycoprotein IIbIIIa inhibition. PMID- 17334519 TI - Prospective study of polymorphisms of the protein Z-dependent protease inhibitor and risk of venous thromboembolism. PMID- 17334520 TI - Association of low protein Z levels with ischemic stroke in young women. PMID- 17334521 TI - Fondaparinux is an effective alternative anticoagulant in pregnant women with high risk of venous thromboembolism and intolerance to low-molecular-weight heparins and heparinoids. PMID- 17334522 TI - Perioperative bridging with fondaparinux in a woman with antithrombin deficiency. PMID- 17334523 TI - Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity. AB - This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage. PMID- 17334524 TI - In silico analysis identifies a C3HC4-RING finger domain of a putative E3 ubiquitin-protein ligase located at the C-terminus of a polyglutamine-containing protein. AB - Almost identical polyglutamine-containing proteins with unknown structures have been found in human, mouse and rat genomes (GenBank AJ277365, AF525300, AY879229). We infer that an identical new gene (RING) finger domain of real interest is located in each C-terminal segment. A three-dimensional (3-D) model was generated by remote homology modeling and the functional implications are discussed. The model consists of 65 residues from terminal position 707 to 772 of the human protein with a total length of 796 residues. The 3-D model predicts a ubiquitin-protein ligase (E3) as a binding site for ubiquitin-conjugating enzyme (E2). Both enzymes are part of the ubiquitin pathway to label unwanted proteins for subsequent enzymatic degradation. The molecular contact specificities are suggested for both the substrate recognition and the residues at the possible E2 binding surface. The predicted structure, of a ubiquitin-protein ligase (E3, enzyme class number 6.3.2.19, CATH code 3.30.40.10.4) may contribute to explain the process of ubiquitination. The 3-D model supports the idea of a C3HC4-RING finger with a partially new pattern. The putative E2-binding site is formed by a shallow hydrophobic groove on the surface adjacent to the helix and one zinc finger (L722, C739, P740, P741, R744). Solvent-exposed hydrophobic amino acids lie around both zinc fingers (I717, L722, F738, or P765, L766, V767, V733, P734). The 3-D structure was deposited in the protein databank theoretical model repository (2B9G, RCSB Protein Data Bank, NJ). PMID- 17334525 TI - Techniques used to identify the Brazilian variant of HIV-1 subtype B. AB - The purpose of the present study was to compare the sensitivity and specificity of V3 enzyme immunoassay (solid phase EIA and EIA inhibition) and restriction fragment length polymorphism (RFLP) with the DNA sequencing "gold standard" to identify the Brazilian HIV-1 variants of subtype B and B"-GWGR. Peripheral blood mononuclear cells were collected from 61 HIV-1-infected individuals attending a clinic in Sao Paulo. Proviral DNA was amplified and sequentially cleaved with the Fok I restriction enzyme. Plasma samples were submitted to a V3-loop biotinylated synthetic peptide EIA. Direct partial DNA sequencing of the env gene was performed on all samples. Based on EIA results, the sensitivity for detecting B GPGR was 70%, compared to 64% for the Brazilian variant B"-GWGR while, the specificity of B-GPGR detection was 85%, compared to 88% for GWGR. The assessment of RFLP revealed 68% sensitivity and 94% specificity for the B-GPGR strain compared to 84 and 90% for the B"-GWGR variant. Moreover, direct DNA sequencing was able to detect different base sequences corresponding to amino acid sequences at the tip of the V3 loop in 22 patients. These results show a similar performance of V3 serology and RLFP in identifying the Brazilian variant GWGR. However, V3 peptide serology may give indeterminate results. Therefore, we suggest that V3 serology be used instead of DNA sequencing where resources are limited. Samples giving indeterminate results by V3 peptide serology should be analyzed by direct DNA sequencing to distinguish between B-GPGR and the Brazilian variant B"-GWGR. PMID- 17334526 TI - Lipolysis of emulsion models of triglyceride-rich lipoproteins is altered in male patients with abdominal aorta aneurysm. AB - Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 +/- 5 years) with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 +/- 5 years) participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and (3)H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR) of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with (3)H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 +/- 0.017 vs 0.039 +/- 0.019 min-1; P < 0.05), but the FCR of 14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm. PMID- 17334527 TI - Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension. AB - Essential hypertension is a disease multifactorially triggered by genetic and environmental factors. The contribution of genetic polymorphisms of the renin angiotensin-aldosterone system and clinical risk factors to the development of resistant hypertension was evaluated in 90 hypertensive patients and in 115 normotensive controls living in Southwestern Brazil. Genotyping for insertion/deletion of angiotensin-converting enzyme, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, aldosterone synthase C344T, and mineralocorticoid receptor A4582C polymorphisms was performed by PCR, with further restriction analysis when required. The influence of genetic polymorphisms on blood pressure variation was assessed by analysis of the odds ratio, while clinical risk factors were evaluated by logistic regression. Our analysis indicated that individuals who carry alleles 235-T, 1166-A, 344-T, or 4582-C had a significant risk of developing resistant hypertension (P < 0.05). Surprisingly, when we tested individuals who carried the presumed risk genotypes A1166C, C344T, and A4582C we found that these genotypes were not associated with resistant hypertension. However, a gradual increase in the risk to develop resistant hypertension was detected when the 235-MT and TT genotypes were combined with one, two or three of the supposedly more vulnerable genotypes - A1166C (AC/AA), C344T (TC/TT) and A4582C (AC/CC). Analysis of clinical parameters indicated that age, body mass index and gender contribute to blood pressure increase (P < 0.05). These results suggest that unfavorable genetic renin angiotensin-aldosterone system patterns and clinical risk variables may contribute to increasing the risk for the development of resistant hypertension in a sample of the Brazilian population. PMID- 17334528 TI - Antagonic effect of the inhibition of inducible nitric oxide on the mortality of mice acutely infected with Escherichia coli and Bacteroides fragilis. AB - Sepsis, the leading cause of death in intensive care units, is associated with overproduction of nitric oxide (NO) due to inducible NO synthase (iNOS), responsible for some of the pathologic changes. Aminoguanidine (AG) is a selective iNOS inhibitor with reported inconsistent actions in sepsis. To investigate the influence of iNOS, we studied models of acute bacterial sepsis using acute challenges with aerobic (Escherichia coli) and anaerobic (Bacteroides fragilis) bacteria in the presence of AG. Six-week-old, 23 g, male and female BALB/c and C57Bl/6j mice, in equal proportions, were inoculated (ip) with bacteria in groups of 4 animals for each dose and each experiment in the absence or presence of AG (50 mg/kg, ip, starting 24 h before challenge and daily until day 6) and serum nitrate was measured by chemiluminescence. Both types of bacteria were lethal to mice, with an LD50 of 6 nephelometric units (U) for E. coli and 8 U for B. fragilis. Nitrate production peaked on the second day after E. coli inoculation with 8 and 6 U (P < 0.05), but was absent after non-lethal lower doses. After challenge with B. fragilis this early peak occurred at all tested doses after 24 h, including non-lethal ones (P < 0.05). AG-treated mice challenged with E. coli presented higher survival (P < 0.05) and increased LD50. AG-treated mice challenged with B. fragilis had lower LD50 and higher mortality. Control AG-treated animals presented no toxic effects. The opposite effect of iNOS blockade by AG in these models could be explained by restriction of oxygen for immune cells or an efficient action of NO in anaerobic localized infections. The antagonic role of NO production observed in our bacterial models could explain the reported discrepancy of NO action in sepsis. PMID- 17334529 TI - Opposite lipemic response of Wistar rats and C57BL/6 mice to dietary glucose or fructose supplementation. AB - The metabolic effects of carbohydrate supplementation in mice have not been extensively studied. In rats, glucose- and fructose-rich diets induce hypertriacylglycerolemia. In the present study, we compared the metabolic responses to two monosaccharide supplementations in two murine models. Adult male Wistar rats (N = 80) and C57BL/6 mice (N = 60), after 3 weeks on a standardized diet, were submitted to dietary supplementation by gavage with glucose (G) or fructose (F) solutions (500 g/L), 8 g/kg body weight for 21 days. Glycemia was significantly higher in rats after fructose treatment (F: 7.9 vs 9.3 mM) and in mice (G: 6.5 vs 10 and F: 6.6 vs 8.9 mM) after both carbohydrate treatments. Triacylglycerolemia increased significantly 1.5 times in rats after G or F supplementation. Total cholesterol did not change with G treatment in rats, but did decrease after F supplementation (1.5 vs 1.4 mM, P < 0.05). Both supplementations in rats induced insulin resistance, as suggested by the higher Homeostasis Model Assessment Index. In contrast, mice showed significant decreases in triacylglycerol (G: 1.8 vs 1.4 and F: 1.9 vs 1.4 mM, P < 0.01) and total cholesterol levels (G and F: 2.7 vs 2.5 mM, P < 0.05) after both monosaccharide supplementations. Wistar rats and C57BL/6 mice, although belonging to the same family (Muridae), presented opposite responses to glucose and fructose supplementation regarding serum triacylglycerol, free fatty acids, and insulin levels after monosaccharide treatment. Thus, while Wistar rats developed features of plurimetabolic syndrome, C57BL/6 mice presented changes in serum biochemical profile considered to be healthier for the cardiovascular system. PMID- 17334530 TI - Effect of saline infusion for the maintenance of blood volume on pulmonary gas exchange during temporary abdominal aortic occlusion. AB - We analyzed the effects of saline infusion for the maintenance of blood volume on pulmonary gas exchange in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. We studied 20 adult mongrel dogs weighing 12 to 23 kg divided into two groups: ischemia-reperfusion group (IRG, N = 10) and IRG submitted to saline infusion for the maintenance of mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, N = 10). All animals were anesthetized and maintained on spontaneous ventilation. After obtaining baseline measurements, occlusion of the supraceliac aorta was performed by the inflation of a Fogarty catheter. After 60 min of ischemia, the balloon was deflated and the animals were observed for another 60 min of reperfusion. The measurements were made at 10 and 45 min of ischemia, and 5, 30, and 60 min of reperfusion. Pulmonary gas exchange was impaired in the IRG-SS group as demonstrated by the increase of the alveolar-arterial oxygen difference (21 +/- 14 in IRG-SS vs 11 +/ 8 in IRG after 60 min of reperfusion, P = 0.004 in IRG-SS in relation to baseline values) and the decrease of oxygen partial pressure in arterial blood (58 +/- 15 in IRG-SS vs 76 +/- 15 in IRG after 60 min of reperfusion, P = 0.001 in IRG-SS in relation to baseline values), which was correlated with the highest degree of pulmonary edema in morphometric analysis (0.16 +/- 0.06 in IRG-SS vs 0.09 +/- 0.04 in IRG, P = 0.03 between groups). There was also a smaller ventilatory compensation of metabolic acidosis after the reperfusion. We conclude that infusion of normal saline worsened the gas exchange induced by pulmonary reperfusion injury in this experimental model. PMID- 17334531 TI - The combination of atorvastatin and ethanol is not more hepatotoxic to rats than the administration of each drug alone. AB - Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group) consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10% ethanol (v/v) ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase) from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption) was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance. PMID- 17334532 TI - Antimicrobial activity of the essential oil from Lippia sidoides, carvacrol and thymol against oral pathogens. AB - Dental caries and periodontal disease are associated with oral pathogens. Several plant derivatives have been evaluated with respect to their antimicrobial effects against such pathogenic microorganisms. Lippia sidoides Cham (Verbenaceae), popularly known as "Alecrim-pimenta" is a typical shrub commonly found in the Northeast of Brazil. Many plant species belonging to the genus Lippia yield very fragrant essential oils of potential economic value which are used by the industry for the commercial production of perfumes, creams, lotions, and deodorants. Since the leaves of L. sidoides are also extensively used in popular medicine for the treatment of skin wounds and cuts, the objective of the present study was to evaluate the composition and antimicrobial activity of L. sidoides essential oil. The essential oil was obtained by hydro-distillation and analyzed by GC-MS. Twelve compounds were characterized, having as major constituents thymol (56.7%) and carvacrol (16.7%). The antimicrobial activity of the oil and the major components was tested against cariogenic bacterial species of the genus Streptococcus as well as Candida albicans using the broth dilution and disk diffusion assays. The essential oil and its major components thymol and carvacrol exhibited potent antimicrobial activity against the organisms tested with minimum inhibitory concentrations ranging from 0.625 to 10.0 mg/mL. The most sensitive microorganisms were C. albicans and Streptococcus mutans. The essential oil of L. sidoides and its major components exert promising antimicrobial effects against oral pathogens and suggest its likely usefulness to combat oral microbial growth. PMID- 17334533 TI - A double-blind comparison of the effect of the antipsychotics haloperidol and olanzapine on sleep in mania. AB - The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean +/- SD final dosage: 5.8 +/- 3.8 mg) or olanzapine (mean +/- SD final dosage: 13.6 +/- 6.9 mg) in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopathology and illness severity were rated respectively with the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions - Bipolar version (CGI-BP). There was a significant improvement in the YMRS and CGI-BP scores at the end of the study for both groups. Mixed ANOVA used to compare the polysomnographic measures of both drugs demonstrated significant improvement in sleep measures with olanzapine. In the olanzapine group, statistically significant time-drug interaction effects on sleep continuity measures were observed: sleep efficiency (mean +/- SEM pre-treatment value: 6.7 +/- 20.3%; after-treatment: 85.7 +/- 10.9%), total wake time (pre treatment: 140.0 +/- 92.5 min; after-treatment: 55.2 +/- 44.2 min), and wake time after sleep onset (pre-treatment: 109.7 +/- 70.8 min; after-treatment: 32.2 +/- 20.7 min). Conversely, improvement of polysomnographic measures was not observed for the haloperidol group (P > 0.05). These results suggest that olanzapine is more effective than haloperidol in terms of sleep-promoting effects, although olanzapine is comparatively as effective as haloperidol in treating mania. Polysomnography records should provide useful information on how manic states can be affected by psychopharmacological agents. PMID- 17334534 TI - Use of alcohol among the inhabitants of the 107 largest cities in Brazil--2001. AB - Alcohol is part of the history of humanity, seemingly as a result of countless factors including the easy production of alcoholic beverages in practically all regions of the world. The authors studied aspects of the use of and the dependence on alcohol in Brazil, through a household survey conducted by Centro Brasileiro de Informacoes sobre Drogas Psicotropicas (CEBRID). A total of 8,589 interviews were held in 107 of the largest cities in Brazil, all of them with more than 200 thousand inhabitants. The study was planned to gather information within the household environment about a stratified probabilistic sample obtained in three selection phases: 1) the censitaire sectors for each municipality, 2) a systematic randomized sampling, and 3) drafting a respondent by lot in each household to provide information. Approximately 11.2% of the subjects were concerned with their own consumption of alcohol. The signs/symptoms of the syndrome of dependence evident in a greater percentage were the desire to stop or reduce the use of alcohol and to stop or reduce resorting to alcoholic beverages more often than desired, as reported by 14.5 and 9.4% of the respondents, respectively. The regions in Brazil with the highest percentage of dependents were the North (16.3%) and the Northeast (19.9%). According to the estimates obtained in the survey, 5.2% of the teenagers were concerned about the use of alcohol. The estimates obtained in this survey reveal a need to implant specific preventive programs for the problem of alcohol, especially for the very young. PMID- 17334535 TI - Mental rotation of anthropoid hands: a chronometric study. AB - It has been shown that mental rotation of objects and human body parts is processed differently in the human brain. But what about body parts belonging to other primates? Does our brain process this information like any other object or does it instead maximize the structural similarities with our homologous body parts? We tried to answer this question by measuring the manual reaction time (MRT) of human participants discriminating the handedness of drawings representing the hands of four anthropoid primates (orangutan, chimpanzee, gorilla, and human). Twenty-four right-handed volunteers (13 males and 11 females) were instructed to judge the handedness of a hand drawing in palm view by pressing a left/right key. The orientation of hand drawings varied from 0 masculine (fingers upwards) to 90 masculine lateral (fingers pointing away from the midline), 180 masculine (fingers downwards) and 90 masculine medial (finger towards the midline). The results showed an effect of rotation angle (F(3, 69) = 19.57, P < 0.001), but not of hand identity, on MRTs. Moreover, for all hand drawings, a medial rotation elicited shorter MRTs than a lateral rotation (960 and 1169 ms, respectively, P < 0.05). This result has been previously observed for drawings of the human hand and related to biomechanical constraints of movement performance. Our findings indicate that anthropoid hands are essentially equivalent stimuli for handedness recognition. Since the task involves mentally simulating the posture and rotation of the hands, we wondered if "mirror neurons" could be involved in establishing the motor equivalence between the stimuli and the participants' own hands. PMID- 17334536 TI - Effect of Helicobacter pylori infection and acid blockade by lansoprazole on clarithromycin bioavailability. AB - The effect of proton pump inhibitors and Helicobacter pylori infection on the bioavailability of antibiotics is poorly understood. We determined the effects of 5-day oral administration of 60 mg lansoprazole on the bioavailability of clarithromycin in individuals with and without H. pylori infection. Thirteen H. pylori-infected and 10 non-infected healthy volunteers were enrolled in a study with an open-randomized two-period crossover design and a 21-day washout period between phases. Plasma concentrations of clarithromycin in subjects with and without lansoprazole pre-treatment were measured by liquid chromatography coupled to a tandem mass spectrometer. Clarithromycin Cmax and AUC0-10 h were significantly reduced after lansoprazole administration. In addition, lansoprazole treatment of the H. pylori-positive group resulted in a statistically significant greater reduction in Cmax (40 vs 15%) and AUC0-10 h (30 vs 10%) compared to lansoprazole-treated H. pylori-negative subjects. Thus, treatment with lansoprazole for 5 days reduced bioavailability of clarithromycin, irrespective of H. pylori status. This reduction, however, was even more pronounced in H. pylori-infected individuals. PMID- 17334537 TI - Endothelin-1 receptors play a minor role in the protection against acute Trypanosoma cruzi infection in mice. AB - Chagas' disease, caused by the protozoan Trypanosoma cruzi, is a major cause of cardiovascular disability in countries where it is endemic. Damage to the heart microvasculature has been proposed to be an important factor in the pathogenesis of heart dysfunction. Endothelin-1 (ET-1) is a potent vasoconstrictor and exerts its effects via specific ET A and ET B receptors. A few studies have suggested a role for ET-1 and its receptors in the pathogenesis of Chagas' disease. We investigated the effects of treatment with bosentan, an ET A/ET B receptor antagonist, on the course of T. cruzi infection (Y strain) in C57Bl/6 mice. Treatment with bosentan (100 mg kg-1 day-1) was given per os starting day 0 after infection until sacrifice. Bosentan significantly increased myocardial inflammation, with no effects on parasitemia. Although the total number of nests was similar, a lower number of intact amastigote nests was found in the heart of bosentan-treated animals. Bosentan failed to affect the infection-associated increase in the cardiac levels of the cytokines IFN-g and TNF-a and the chemokines CCL2/MCP-1, CCL3/MIP-1a and CCL5/RANTES. In vitro, pre-incubation with ET-1 (0.1 microM) 4 h before infection enhanced the uptake of the parasites by peritoneal macrophages, and this effect was abrogated when macrophages were pre treated with bosentan (1 microM) 15 min before incubation with ET-1. However, ET 1 did not alter killing of intracellular parasites after 48 h of in vitro infection. Our data suggest that bosentan-treated mice have a delay in controlling parasitism which is compensated for exacerbated inflammation. Infection is eventually controlled in these animals and lethality is unchanged, demonstrating that ET-1 plays a minor role in the protection against acute murine T. cruzi infection. PMID- 17334538 TI - Sympathetic activation in rats with L-NAME-induced hypertension. AB - We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means +/- SEM) 2.47 +/- 0.08 to 2.14 +/- 0.07; conscious, 7 days: from 2.85 +/- 0.13 to 2.07 +/- 0.33; anesthetized, 2 days: from 3.00 +/- 0.09 to 1.83 +/- 0.25 and anesthetized, 7 days: from 3.56 +/- 0.11 to 1.53 +/- 0.10 mmHg mL-1 min-1) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 +/- 4.5 to 96 +/- 4; anesthetized: from 118 +/- 1.5 to 104 +/- 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension. PMID- 17334539 TI - Long-term loss of color vision after exposure to mercury vapor. AB - We evaluated the color vision of 24 subjects (41.6 +/- 6.5 years; 6 females) who worked in fluorescent lamp industries. They had been occupationally exposed to mercury vapor (10.6 +/- 5.2 years) and had been away from the source of exposure for 6.4 +/- 4.04 years. Mean urinary concentration of mercury was 40.6 +/- 36.4 microg/g creatinine during or up to 1 year after exposure and 2.71 +/- 1.19 microg/g creatinine at the time of color vision testing or up to 1 year thereafter. All patients were diagnosed with chronic mercury intoxication, characterized by clinical symptoms and neuropsychological alterations. A control group (N = 36, 48.6 +/- 11.9 years, 10 females, 1.5 +/- 0.47 microg mercury/g creatinine) was subjected to the same tests. Inclusion criteria for both groups were Snellen VA 20/30 or better and absence of known ophthalmologic pathologies. Color discrimination was assessed with the Farnsworth D-15 test (D-15) and with the Lanthony D-15d test (D-15d). Significant differences were found between the two eyes of the patients (P < 0.001) in both tests. Results for the worst eye were also different from controls for both tests: P = 0.014 for D-15 and P < 0.001 for D-15d. As shown in previous studies, the D-15d proved to be more sensitive than the D-15 for the screening and diagnosis of the color discrimination losses. Since color discrimination losses were still present many years after the end of exposure, they may be considered to be irreversible, at least under the conditions of the present study. PMID- 17334540 TI - Mercury toxicity in the Amazon: contrast sensitivity and color discrimination of subjects exposed to mercury. AB - We measured visual performance in achromatic and chromatic spatial tasks of mercury-exposed subjects and compared the results with norms obtained from healthy individuals of similar age. Data were obtained for a group of 28 mercury exposed subjects, comprising 20 Amazonian gold miners, 2 inhabitants of Amazonian riverside communities, and 6 laboratory technicians, who asked for medical care. Statistical norms were generated by testing healthy control subjects divided into three age groups. The performance of a substantial proportion of the mercury exposed subjects was below the norms in all of these tasks. Eleven of 20 subjects (55%) performed below the norms in the achromatic contrast sensitivity task. The mercury-exposed subjects also had lower red-green contrast sensitivity deficits at all tested spatial frequencies (9/11 subjects; 81%). Three gold miners and 1 riverine (4/19 subjects, 21%) performed worse than normal subjects making more mistakes in the color arrangement test. Five of 10 subjects tested (50%), comprising 2 gold miners, 2 technicians, and 1 riverine, performed worse than normal in the color discrimination test, having areas of one or more MacAdam ellipse larger than normal subjects and high color discrimination thresholds at least in one color locus. These data indicate that psychophysical assessment can be used to quantify the degree of visual impairment of mercury-exposed subjects. They also suggest that some spatial tests such as the measurement of red-green chromatic contrast are sufficiently sensitive to detect visual dysfunction caused by mercury toxicity. PMID- 17334541 TI - Neuropsychological dysfunction related to earlier occupational exposure to mercury vapor. AB - We assessed the neuropsychological test performances of 26 patients (mean age = 41.5 +/- 6.1 years; mean years of education = 9.8 +/- 1.8; 20 males) diagnosed with chronic occupational mercurialism who were former workers at a fluorescent lamp factory. They had been exposed to elemental mercury for an average of 10.2 +/- 3.8 years and had been away from this work for 6 +/- 4.7 years. Mean urinary mercury concentrations 1 year after cessation of work were 1.8 +/- 0.9 microg/g creatinine. Twenty control subjects matched for age, gender, and education (18 males) were used for comparison. Neuropsychological assessment included attention, inhibitory control, verbal and visual memory, verbal fluency, manual dexterity, visual-spatial function, executive function, and semantic knowledge tests. The Beck Depression Inventory and the State and Trait Inventory were used to assess depression and anxiety symptoms, respectively. The raw score for the group exposed to mercury indicated slower information processing speed, inferior performance in psychomotor speed, verbal spontaneous recall memory, and manual dexterity of the dominant hand and non-dominant hand (P < 0.05). In addition, the patients showed increased depression and anxiety symptoms (P < 0.001). A statistically significant correlation (Pearson) was demonstrable between mean urinary mercury and anxiety trait (r = 0.75, P = 0.03). The neuropsychological performances of the former workers suggest that occupational exposure to elemental mercury has long-term effects on information processing and psychomotor function, with increased depression and anxiety also possibly reflecting the psychosocial context. PMID- 17334543 TI - Pharyngeal dimensions in healthy men and women. AB - INTRODUCTION: Epidemiological studies reveal a high male prevalence of obstructive sleep apnea syndrome. A possible explanation for this male predominance is the existence of anatomical differences in the upper airway between men and women. METHODS: The upper airways of 10 male and 10 female healthy volunteers were prospectively evaluated by magnetic resonance imaging. Anatomical pharyngeal and column cross-sectional linear measurements were made in sagittal T1 and axial T1 and T2 weighted fast spin-echo images. RESULTS: Men had significantly greater mean sagittal pharyngeal structural dimensions compared to women for all structures with the exception of the craniocaudal length of the soft palate and the thickness of the submentonian fat. In contrast, cross sectional linear dimensions were similar in men and women with the exception of the laterolateral tongue length, which was greater in men. All mean linear measurements of the pharyngeal air column were similar in men and women at all studied levels. CONCLUSIONS: Men and women present pharyngeal air columns with similar dimensions, but in women this column is surrounded by smaller structures, which might imply a smaller effort to keep its patency. Our data suggest the existence of an anatomical protective factor in women against the upper airway collapse. PMID- 17334544 TI - Patterns of detection and optical correction among ophthalmologists. AB - OBJECTIVE: To verify age of first ophthalmic evaluation and optical prescription along with present optical correction among ophthalmologists of different age groups. METHODS: A cross-sectional study was conducted with a nonprobabilistic sample (n = 578) of ophthalmologists and resident physicians using a self administered questionnaire. RESULTS: The first ophthalmologic exam was undergone before age 7 for 33.3% of the ophthalmologists aged between 23 and 30 years, for 25.8% of those aged from 31 to 42 , and for 15.8% of those aged from 43 to 76 years (P < 0.0005). The first ophthalmologic exam was undergone at 8 to 22 years of age for 60.7% of the ophthalmologists aged between 23 and 30, for 54.9% of those aged between 31 and 42, and for 47.4% of those aged from 43 to 76 years of age. Use of the first optical prescription (eyeglasses) between 0 and 7 years was reported by 10.0%, from 8 to 20 years of age by 59.6%, from 21 to 40 years by 18.1%, and 41 years or older by 12.3% . Present use of optical correction was reported by 69.0%. Concerning type of corrective device chosen, 63.7% wore only eyeglasses, 29.8% wore eyeglasses and contact lenses, and 6.5% wore contact lenses only. CONCLUSION: Among the sample of opthalmologists, the first ophthalmic evaluation and corresponding optical correction usually occurred relatively late (8 to 20 years of age). However, in the younger group of ophthalmologists, there was a highly significant increase in the number of subjects who had undergone an ophthalmologic exam before age 7. Eyeglasses were reported as the correction of choice by those in all age groups. PMID- 17334545 TI - Multicenter study of perioperative evaluation for noncardiac surgeries in Brazil (EMAPO). AB - INTRODUCTION: The accuracy of perioperative evaluation methods available is better than chance, but their performance is not ideal. OBJECTIVES: To compare a new evaluation method (EMAPO) to the American College of Physicians method for determining the risk of cardiovascular complications in noncardiac surgeries and to look for new influencing variables. METHODS: Evaluations through EMAPO and the American College of Physicians method were employed for 700 patients. Cardiac events and deaths were recorded, the risk variables related to the occurrence of complications were verified, and the models were compared by analyzing the areas under the receiver operating characteristic curves. RESULTS: Mortality rate was 3.4%, and the incidence of cardiovascular complications was 5.3%. Renal failure (P = 0.01), major surgery (P = 0.004), and emergency surgery (P = 0.003) were independently related to the occurrence of cardiovascular complications. The two methods produced similar results. CONCLUSION: EMAPO is as good as the American College of Physicians method in determining the risk of cardiovascular complications in noncardiac surgeries. New variables related to surgical risk were identified. PMID- 17334546 TI - Semiquantitative assessment of surgical lung biopsy: predictive value and impact on survival of patients with diffuse pulmonary infiltrate. AB - PURPOSE: Surgical lung biopsy has been studied in distinct populations, mostly going beyond clinical issues to impinge upon routine histopathological diagnostic information in diffuse infiltrates; however, detailed tissue analyses have rarely been performed. The present study was designed to investigate the prognostic contribution provided by detailed tissue analysis in diffuse infiltrates. METHODS: Medical records and surgical lung biopsies from the period of 1982 to 2003 of 63 patients older than 18 years with diffuse infiltrates were retrospectively examined. Lung parenchyma was histologically divided into 4 anatomical compartments: interstitium, airways, vessels, and alveolar spaces. Histological changes throughout these anatomical compartments were then evaluated according to their acute or chronic evolutional character. A semiquantitative scoring system was applied to histologic findings to evaluate the intensity and extent of the pathological process. We applied logistic regression to predict the risk of death associated with acute and chronic histological changes and to estimate the odds ratios for each of the independent variables in the model. RESULTS: Impact on survival was found for male gender (P = 0.03), presence of diffuse alveolar damage (P = 0.001), and chronic histological changes (P = 0.0004) on biopsy. Thus, being male was associated with a slightly lower risk (O.R. = 0.18; P=0.03) of dying than being female. Death risk was increased 17 times in the presence of acute histological changes such as diffuse alveolar damage and 2.5 times in the presence of chronic histological changes. CONCLUSION: Detailed analysis of histological specimens can provide more than a nosological diagnosis: this approach can provide valuable information concerning prognosis. PMID- 17334547 TI - Late results of catheter-directed recombinant tissue plasminogen activator fibrinolytic therapy of iliofemoral deep venous thrombosis. AB - PURPOSE: To evaluate the efficacy of catheter-directed low-dose recombinant tissue-type plasminogen activator infusion in the treatment of iliofemoral deep venous thrombosis and prevention of post-thrombotic syndrome. METHOD: Eighteen patients (out of 260 evaluated) with acute iliofemoral deep venous thrombosis and no previous evidence of venous insufficiency were prospectively selected for thrombolytic therapy. Catheter-directed low-dose recombinant tissue-type plasminogen activator (1 mg/h) was infused into the thrombotic segments. RESULTS: Effective fibrinolysis was achieved in 14 of 18 cases, with correlation between effective fibrinolysis and major/complete resolution of acute signs and symptoms (P <.01). There were no episodes of major complications. Four patients presented with early rethrombosis (1 to 8 weeks). Individuals were followed for a period up to 131 weeks (average, 85.2). The incidence of clinical signs and symptoms of venous insufficiency and duplex-scan findings of valvular reflux was significantly lower in the patients in which lytic therapy succeeded and patency was kept, compared with patients experiencing acute therapeutic failure or rethrombosis (P <.01). CONCLUSIONS: Low-dose recombinant tissue-type plasminogen activator fibrinolytic therapy is safe and effective in the treatment of acute iliofemoral venous thrombosis. The late evolution as revealed clinically and by ultrasound was superior in patients for whom lytic therapy was effective. PMID- 17334548 TI - Endoscopic study of the intranasal ostium in external dacryocystorhinostomy postoperative. Influence of saline solution and 5-fluorouracil. AB - PURPOSE: To study, through endoscopy, the postoperative structural changes of the intranasal ostium following external dacryocystorhinostomy and to evaluate the influence of saline solution and 5-fluorouracil. METHODS: Fifty patients were distributed into the following groups: Group SS-dacryocystorhinostomy and an injection of saline solution during surgery (13 patients); Group 5--FU1 dacryocystorhinostomy and an injection of 5 fluorouracil during surgery (17 patients); Group C--dacryocystorhinostomy only (11 patients); Group 5--FU3 dacryocystorhinostomy and 3 injections, 1 during surgery and 1 on the third and fifth postsurgical days (9 patients). RESULTS: Pair-wise group comparisons using the nonparametric Mann-Whitney test revealed that there was a significant reduction of the ostium area only in Group 5-FU1 vs. Group SS on the 60th postoperative day (P <.01); however, a comparative study among the 4 groups using the Kruskal-Wallis test showed no significant changes in the ostium area on the 60th postoperative day. The ostium area within groups at the 30th vs 60th postoperative day was significantly reduced for Group C (P < .05; Mann-Whitney test); no significant changes were found for the other groups. DISCUSSION: These results suggest that the use of 5-fluorouracil in external dacryocystorhinostomy does not significantly influence the final size of the surgical fistula as determined 2 months postsurgery. PMID- 17334549 TI - Digestive tract microbiota in healthy volunteers. AB - PURPOSE: The aim of this study was to standardize the methods of sample collection of mucus from the digestive tract and to determine the microbiota in healthy volunteers from Brazil, collecting samples from the mouth, esophagus, stomach, duodenum, jejunum, ileum, colon, and rectum. METHODS: Microbiota of selected healthy volunteers from the oral cavity (n=10), the esophagus (n=10), the upper digestive tract (n=20), and the lower digestive tract (n=24) were evaluated through distinct collection methods. Collection methods took into account the different sites, using basic scraping and swabbing techniques, stimulated saliva from the oral cavity, irrigation-aspiration with sterile catheters especially designed for the esophagus, a probe especially designed for upper digestive tract, and a special catheter for the lower digestive tract. RESULTS: (i) Mixed microbiota were identified in the oral cavity, predominantly Gram-positive aerobic and anaerobic cocci; (ii) transitional flora mainly in the esophagus; (iii) Veillonella sp, Lactobacillus sp, and Clostridium sp in the stomach and duodenum; (iv) in the jejunum and upper ileum, we observed Bacteroides sp, Proteus sp, and Staphylococcus sp, in addition to Veillonella sp; (v) in the colon, the presence of "nonpathogenic" anaerobic bacteria Veillonella sp (average 10(5) UFC) indicates the existence of a low oxidation-reduction potential environment, which suggests the possibility of adoption of these bacteria as biological markers of total digestive tract health. CONCLUSIONS: The collection methods were efficient in obtaining adequate samples from each segment of the total digestive tract to reveal the normal microbiota. These procedures are safe and easily reproducible for microbiological studies. PMID- 17334550 TI - Unmeasured anions account for most of the metabolic acidosis in patients with hyperlactatemia. AB - PURPOSE: To characterize the different components of metabolic acidosis in patients with hyperlactatemia in order to determine the degree to which lactate is responsible for the acidosis and the relevance that this might have in the outcome of these patients. METHODS: Arterial blood gas, arterial lactate, Na+, K+, Ca2+, Mg2+, Cl-, phosphate, albumin, and creatinine were measured on admission to make a diagnosis of the acid-base disturbances present. Intensive Care Unit and in-hospital mortality were also recorded. RESULTS: A total of 58 patients with hyperlactatemia were included. They usually had a mild acidemia (pH 7.31 +/- 0.12) and a significantly high Standard Base Deficit (7.6 +/- 6.7 mEq/L). In addition to lactate (4.3 +/- 2.3 mEq/L), chloride (106.9 +/- 9.5 mEq/L) and unmeasured anions (8.6 +/- 5.0 mEq/L) accounted for the metabolic acidosis. Unmeasured anions were primarily responsible for the acidosis in both Intensive Care Unit survivors and nonsurvivors (44.7% +/- 26.0% and 46.0% +/- 17.5%, respectively, P = 0.871). Lactate contributed in similar percentages to the acidosis in both groups (23.0% +/- 11.8% and 24.2% +/- 9.7% in Intensive Care Unit survivors and nonsurvivors, respectively; P = 0.753). Correlation between Standard Base Deficit and lactate was found only in Intensive Care Unit nonsurvivors (r = 0.662, P < 0.01). DISCUSSION: Hyperlactatemia is usually accompanied by metabolic acidemia, but lactate is responsible for a minor percentage of the acidosis; unmeasured anions account for most of the acidosis in patients with hyperlactatemia. The percentage of the acidosis due to hyperlactatemia was not relevant in terms of outcome. PMID- 17334551 TI - Changes in joint kinematics in children with cerebral palsy while walking with and without a floor reaction ankle-foot orthosis. AB - INTRODUCTION: The floor reaction ankle-foot orthosis is commonly prescribed in the attempt to decrease knee flexion during the stance phase in the cerebral palsy (CP) gait. Reported information about this type of orthosis is insufficient. PURPOSE: The purpose of this study was to determine the effect of clinically prescribed floor reaction ankle-foot orthosis on kinematic parameters of the hip, knee and ankle in the stance phase of the gait cycle, compared to barefoot walking on children with cerebral palsy. METHODS: A retrospective chart review of 2200 patients revealed that 71 patients (142 limbs) had a diagnosis of diplegia, with no contractures in hip, knee or ankle flexion. Their average age was 12.2 +/- 3.9. All of them were wearing clinically prescribed hinged floor reaction ankle-foot orthosis undergoing a three dimensional gait analysis. We divided the patients in three groups: Group I, with limited extension (maximum knee extension less than 15 masculine); Group II, with moderate limited extension (maximum knee extension between 15 masculine and 30 masculine) and Group III Crouch (maximum knee extension in stance more than 30 masculine). RESULTS: Results indicate the parameters maximum knee extension and ankle dorsiflexion were significant in Group II e III; no change was observed in Group I. The maximum hip extension was not significant in all three groups. CONCLUSION: when indicated to improve the extension of the knees and ankle in the stance of the CP patients floor reaction ankle-foot orthosis was effective. PMID- 17334552 TI - Autopsy-proven causes of death in lungs of patients immunocompromised by secondary interstitial pneumonia. AB - PURPOSE: To present the more frequent associations found in autopsies of immunocompromised patients who developed secondary interstitial pneumonia as well as the risk of death (odds ratio) in having specific secondary interstitial pneumonia according to the cause of immunocompromise. METHOD: From January 1994 to March 2004, 17,000 autopsies were performed at Hospital das Clinicas, Sao Paulo University Medical School. After examining the pathology report review, we selected 558 of these autopsies (3.28%) from patients aged 15 years or more with primary underlying diseases who developed radiologically diffuse infiltrates of the lung during their hospital course and died after secondary interstitial pneumonia (bronchopneumonia, lobar pneumonia, interstitial pneumonia, diffuse alveolar damage, pulmonary recurrence of underlying disease, drug-induced lung disease, cardiogenic pulmonary edema, or pulmonary embolism). Histology slides were reviewed by experienced pathologists to confirm or not the presence of secondary interstitial pneumonia. Statistical analysis included the Fisher exact test to verify any association between histopathology and the cause of immunocompromise; a logistic regression was used to predict the risk of death for specific histological findings for each of the independent variables in the model. RESULTS: Secondary interstitial pneumonia was histologically represented by diffuse interstitial pneumonitis ranging from mild nonspecific findings (n = 213) to a pattern of diffuse alveolar damage (n = 273). The principal causes of immunocompromise in patients with diffuse alveolar damage were sepsis (136 cases), neoplasia (113 cases), diabetes mellitus (37 cases), and transplantation (48 cases). A high risk of death by pulmonary edema was found for patients with carcinoma of colon. Similarly, in patients with lung cancer or cachexia, A high risk of death by bronchopneumonia (OR = 3.6; OR = 2.6, respectively) was found. Pulmonary thromboembolism was associated with an appreciable risk of death (OR = 2.4) in patients with arterial hypertension. The risk of death was also high in patients presenting hepatic cancer (OR = 2.5) or steroid therapy (OR = 2.4) who developed pulmonary hemorrhage as the histological pattern of secondary interstitial pneumonia . The risk of death by lung metastasis was also elevated (OR = 1.6) for patients that were immunosuppressed after radiotherapy. CONCLUSION: Patients with secondary immunosuppression who developed secondary interstitial pneumonia during treatment in hospital should be evaluated to avoid death by diffuse alveolar damage, pulmonary edema, bronchopneumonia, lung hemorrhage, pulmonary thromboembolism, or lung metastasis. The high-risk patients are those immunosuppressed by hematologic disease; those under steroid treatment; or those with colon or hepatic carcinoma, cachexia, or arterial hypertension. PMID- 17334553 TI - Menopause, estrogens, and endothelial dysfunction: current concepts. AB - Menopause is defined as the permanent cessation of menses. Cardiovascular disease is the leading cause of death among postmenopausal women in developed countries. The disparity between the incidence of cardiovascular disease among women in pre- and postmenopause has been ascribed to the actions of endogenous estrogen on the cardiovascular system and, particularly, on the vascular endothelium. The endothelium plays an important role in cardiovascular homeostasis, either through the vascular tonus and its regulation, or through coagulation and the inflammatory response. Endothelial dysfunction is implicated in the genesis of atherosclerosis and other chronic disorders, such as diabetes mellitus and hypertension. The pharmacological use of estrogen exerts influence on the circulating levels of markers of vascular tonus, and inflammation, as well as prothrombotic, and fibrinolytic markers, but the impact of these changes on the atherosclerotic disease is still uncertain. PMID- 17334554 TI - Renal parenchymal malacoplakia with pleural effusion. PMID- 17334555 TI - Recurrence of chagasic megacolon after surgical treatment: clinical, radiological, and functional evaluation. PMID- 17334556 TI - Glandular cystitis: a rare benign condition presenting as a pseudo-tumor of the bladder. PMID- 17334557 TI - Brazilian policy for influenza vaccination and its impact on the health of the elderly. PMID- 17334558 TI - [Does AIDS have a race or color? Data interpretation and health policymaking in Brazil]. AB - Over the last few years we have observed a growing emphasis on a supposed relationship between the AIDS epidemic and the "black population" in Brazil. After undertaking an analysis of the national data base of HIV/AIDS in Brazil, this study examines the sociopolitical context in which public policy with a focus on "race" has been defined. We argue that questions related to the quality of the data, the structuring of the information system itself and the use and interpretation of this information are all essential elements for understanding the process underway. Specifically we aim to show that the available epidemiological data are not sufficient to warrant the interpretation that there is in fact a relationship between the "black population" and AIDS in the country. We stress that the emphasis on this supposed association is part of a more general process of construction of the field of the "health of the black population" in recent years and that this is related to interrelationships between political activism and the State which go far beyond the field of health. PMID- 17334567 TI - [The importance of essential fatty acids and the effect of trans fatty acids in human milk on fetal and neonatal development]. AB - Breastfeeding has a major impact on public health, since human breast milk is the best food for infants up to six months of age. The lipid fraction in human milk is the main source of energy for the infant and supplies essential nutrients such as fat-soluble vitamins and polyunsaturated fatty acids (PUFA). Essential fatty acids (EFA), specifically linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3), are precursors of long-chain polyunsaturated fatty acids (LC PUFA), including docosahexaenoic (DHA) and arachidonic (ARA) acids. Quality of lipids in secreted milk is precisely related to maternal ingestion. LC-PUFAs protect against allergy and infection and are important for visual and cognitive development in infancy. Industrial food processing has introduced the trans fatty acids (TFA) among the nutrients available to the population. TFA can interfere with the metabolism of essential fatty acids by decreasing LC-PUFA synthesis. It is thus important to raise population awareness on the importance of adequate PUFA consumption and reduced TFA intake during prenatal and postnatal development. PMID- 17334568 TI - [Social actors in HIV/AIDS prevention: opposition and interests in educational policy in Mexico, 1994-2000]. AB - Studies and recommendations by health agencies have emphasized the importance of education in HIV-AIDS prevention. Mexico has included topics on sexuality and HIV AIDS in school programs, triggering resistance by some social actors. The current study seeks to clarify the various positions and interests and their influence on the textbook content. A literature search was conducted on the period during which the last educational reform was implemented in Mexico. The discourse analysis focused on the ethnography of communication, which identified: the various actors' positions, arguments, actions, economic and political power, and relations to others. The results show that those who oppose the inclusion of these themes in the school curriculum base their position on tradition, contrary to modernization and secularization of social life, and that their positions range from refusal to raising conditions. Networks have been formed that provide such groups with significant economic and political power. Government has given in to some demands by partially modifying the textbook contents. The current analysis proposes to reflect on the potential repercussions of such actions on the control of the epidemic. PMID- 17334569 TI - [Tuberculosis in Rio de Janeiro prisons, Brazil: an urgent public health problem]. AB - The tuberculosis incidence rate in prisons in Rio de Janeiro State, Brazil, was 30 times higher in 2004 than in the general population and is probably underestimated, particularly given the difficult access to care in the prison setting. To obtain a better estimate, a survey used systematic X-ray screening and showed a prevalence rate of 4.6% in one such detention facility, A (n = 1,052). Two additional surveys, in facilities B (n = 590) and C (n = 1,372), showed even higher prevalence rates (6.3% and 8.6% respectively). A comparison of socio-demographic characteristics between A, B, and C showed a heterogeneous prison population. As compared to facility A, inmates in B and C come from poorer urban communities and have more frequent histories of incarceration and tuberculosis. These differences, consistent with the prevalence data, imply the necessary adaptation of tuberculosis control programs to each detention facility's epidemiological and socio-demographic profile. PMID- 17334571 TI - [Why do men use health services less than women? Explanations by men with low versus higher education]. AB - The objective of this study was to analyze explanations in male discourse for men's relatively limited use of health services, using a qualitative methodology. Representation of caring as a female task, work-related issues, difficult access to services, and lack of services specifically targeting men's health were the main reasons for their limited use of health services. By way of conclusion, the social imagination by which men are viewed as invulnerable leads them to take less care of their own health and expose themselves to greater risk. PMID- 17334570 TI - [Dietary factors and oral cancer: a case-control study in Greater Metropolitan Sao Paulo, Brazil]. AB - Dietary factors associated with oral cancer were investigated in a case-control hospital-based study in the city of Sao Paulo, Brazil, from 1998 to 2002. A total of 835 subjects, 366 with histologically confirmed incident cases of oral-cavity or pharyngeal cancer and 469 controls participated in the study. Dietary data were collected with a food frequency questionnaire (FFQ). Odds ratios (OR) and 95% confidence intervals (95%CI) were obtained from unconditional logistic regression, adjusted for potential confounders. Inverse associations with risk of oral cancer were found for the highest intake of beans, OR = 0.37 (95%CI: 0.22 0.64), raw vegetables, OR = 0.51 (95%CI: 0.29-0.93) and the intermediate tertile of rice and pasta intake, OR = 0.56 (95%CI: 0.38-0.83). Positive associations were observed for the highest intake of eggs, OR = 1.84 (95%CI: 1.23-2.75), potatoes, OR = 2.22 (95%CI: 1.53-3.25), and milk, OR= 1.80 (95%CI: 1.09-2.98). Some traditional Brazilian foods like rice and beans emerged as protective factors against oral cancer, independently of other risk factors. PMID- 17334572 TI - [Governance and regulation in health: challenges for health management in Greater Metropolitan Sao Paulo, Brazil]. AB - This paper discusses the relationship between the public and private sectors in the Unified National Health System (SUS), based on research whose objective was to identify governance strategies and mechanisms for public/private relations in the health sector, considering the search for equity in Greater Metropolitan Sao Paulo, Brazil. Governance was used as an analytical category, with health system regulation as the issue. Municipal and State health secretaries, members of health councils, and SUS staff were interviewed, and the empirical material was classified as: (a) regulatory mechanisms and instruments; (b) power loci; and (c) actors' positions concerning the SUS and its relationship to the private sector. Mechanisms and instruments have been created and used in the municipalities for regulation of their own services. Regulatory measures for the complementary and supplementary healthcare sector are practically nonexistent. There are numerous institutional power loci, seen more as places for submitting demands than as forums for negotiation. Despite some progress, governance appears to be more of a formal issue. Discussion is needed on the relationship between the public and private sectors and its regulation by municipalities in order to improve the health system. PMID- 17334573 TI - [Risk of repeated hospitalizations in elderly users of an academic health center]. AB - The aim of this study was to stratify 305 elderly (> 65 years) treated at an academic health center (Botucatu, Sao Paulo, Brazil) according to risk of repeated hospitalization. Data collection used an instrument to evaluate risk of repeated hospital admissions, including eight health indicators: self-rated health, hospitalizations, doctor visits, diabetes, cardiovascular disease, gender, social support, and age. 56.4% of interviewees presented low probability of repeated hospitalization, as compared to 26.9% medium, 10.5% medium-high, and 6.2% high probability. Combining health indicators with the probability of repeated hospitalization, for elderly classified as medium, medium-high, and high risk compared to low, the relative risk was significant: medium or bad health (2.31); hospitalization (2.38); > 3 doctor visits (1.75); diabetes (2.10); cardiovascular disease (2.76); male gender (1.68); and > 75 years of age (1.62). The instrument was able to stratify elderly at risk of repeated hospitalization and is thus useful for reorganizing public health services. PMID- 17334574 TI - [Dental caries activity in primary dentition, Indaiatuba, Sao Paulo, Brazil, 2004]. AB - This study aimed to verify caries activity and analyze caries experience, treatment needs, and enamel defects in 5-year-old preschool children in Indaiatuba, Sao Paulo State, Brazil. 624 children were selected by systematic random sampling in 2004. WHO criteria were used to measure caries experience and treatment needs. Nyvad et al. diagnostic criteria were used to analyze caries activity. Mann-Whitney and chi-square tests were used to analyze the results, with 5% significance. 40.5% of schoolchildren displayed caries activity. The dfmt was 1.62 (95%CI: 1.35-1.89). Among children with dfmt > 0, the index was 3.81 (95%CI: 3.36-4.26), and 91.4% of these children presented caries activity. Care Index was 12.3%. These results suggest that treatment measures and health promotion should continue to be prioritized, since the control measures and caries interruption during the initial stages are well known. Dental care should especially target schoolchildren with more significant caries experience. PMID- 17334575 TI - [Analysis of rulings by the Brazilian Ministry of Health and reflections on national health policy management]. AB - Ministry of Health rulings and provisions are important policy regulation tools that aim to orient the enforcement of health-related laws passed by the Legislative Branch, under the terms of the 1988 Federal Constitution. Such provisions have played a major role in the health sector, due not only to the number of documents submitted since the late 1990s, but mainly because of this tool's persuasive power in defining health sector policy. The current article aims to foster reflection on both national health policy management in Brazil and the main obstacles to the implementation of health reform operational aspects. The article classified and analyzed Ministry of Health rulings issued from 1990 to 2002. The study highlights the Ministry's centralizing approach and the use of financial and political persuasion tools that subject State and Municipal governments to the system's rules without creating a negotiated and sustained health policy that the country's institutional realities ratify and support. PMID- 17334576 TI - [Descriptive cross-sectional study of hearing-disabled children at the National Institute for Education of the Deaf in Rio de Janeiro, Brazil]. AB - In Brazil, research is scarce on multiple disabilities and hearing disability in particular. Researchers began a pioneering study in 1992, evaluating students from public special education programs, currently focused on hearing disability. The authors evaluated 232 students ranging from 1 to 39 years of age (mean 10.9 years), with male gender prevailing. Consanguinity was present in 7.6% and a family history of deafness in 19%. Gestational complications were recorded in 33% of cases. Normal labor occurred in 72%, and delivery at term in 75%. Neonatal complications were present in 35% of the sample. Environmental causes accounted for 56% of the sample, genetic causes 20.7%, and the remaining 20.7% were classified as idiopathic. The current findings corroborate those from the literature. We believe that this study can spark greater concern for the hearing disabled and that through increased knowledge of this group's characteristics it may foster strategies to facilitate interaction with society as a whole. PMID- 17334577 TI - [Impact of periodontal disease on quality of life for dentate diabetics]. AB - The aim of this study was to evaluate the potential impact of periodontal disease on quality of life in diabetics. A total of 159 dentate diabetic individuals registered at the Municipal Hospital in Itauna, Minas Gerais, Brazil, were examined and interviewed. The clinical periodontal parameters recorded were: gingival bleeding, probing depth, and clinical attachment level. The OHIP-14 form was used to evaluate the impact of periodontal disease on quality of life. In relation to periodontal status, 15.7% of individuals were healthy, 35.2% presented gingivitis, and 49.1% periodontitis (27.7% in the mild-to-moderate and 21.4% in the advanced stages). Association between diagnosis of periodontal disease and impact on quality of life was significant in individuals with periodontitis (p < 0.001). Gingival bleeding, probing depth, and clinical attachment level > 4mm were associated with intensely negative impact on quality of life (p = 0.013, p < 0.001, and p = 0.012 respectively). Diabetics with mild to-moderate and advanced periodontitis had more negative impact on quality of life than those who were periodontally healthy or with gingivitis. PMID- 17334578 TI - [Profiles of multiple causes of death related to HIV/AIDS in the cities of Sao Paulo and Santos, Brazil, 2001]. AB - Following the introduction of highly active antiretroviral therapy (HAART), the HIV-related morbidity-mortality profile has changed. Opportunistic infections are not as prevalent as before, and "pre-AIDS" diseases have become more common, related mostly to the side effects of HAART. This study focused on HIV/AIDS related mortality, based on multiple causes of death among individuals who died of HIV-related causes in the cities of Sao Paulo and Santos, Brazil, in 2001. Grade of Membership (GoM) analysis was used. Three mortality profiles were detected: (1) causes of death normally observed before the introduction of HAART, marked by opportunistic infections; (2) causes of death with mixed characteristics, both pre- and post-HAART; and (3) a residual profile, which did not contemplate HIV disease, but incorporated causes of death associated with the pre and post-HAART periods. It is hoped that the current study will contribute to the understanding of the HIV/AIDS morbidity-mortality scenario and help improve the treatment and care provided by public health services. PMID- 17334579 TI - [Prevalence and characteristics associated with metabolic syndrome in Japanese Brazilians with and without periodontal disease]. AB - This cross-sectional study focused on the relationship between periodontal disease and metabolic syndrome. Data were analyzed from 1,315 Japanese-Brazilians ranging from 30 to 92 years of age, submitted to physical, laboratory, and dental exams. Means and percentages were used in the data description and logistic regression pattern in the analysis of associations among variables. 484 (36.8%) of the 1,315 were edentulous, 215 (16.4%) enjoyed periodontal health, 513 (39%) had gingivitis, 85 (6.5%), showed initial or moderate periodontitis, and 18 (1.4%) suffered from chronic periodontitis. Prevalence of metabolic syndrome was 54.3%, higher among individuals with periodontitis than in the healthy (51.5% vs. 48.8%), but this association was not statistically significant. Individuals with metabolic syndrome showed a worse metabolic and anthropometric profile. PMID- 17334580 TI - [Dengue: sero-epidemiological survey and virological surveillance in Campinas, Sao Paulo, Brazil]. AB - The epidemiology of dengue in the municipality of Campinas, Sao Paulo, Brazil, was studied in 1998 using a randomized sero-epidemiological survey. Epidemiological surveillance data from 1996-2003 were also analyzed, with an emphasis on virological surveillance. 1,260 individuals participated in the survey and had blood samples drawn by finger stick on filter paper. Blood samples were tested by EIA-ICC, an enzyme immunoassay using infected cells as antigen. Dengue antibody prevalence (14.79%) was lower than in other surveys in other States of Brazil, but higher than in two other serological surveys in Sao Paulo State. Dengue antibody prevalence was far higher than the reported case incidence during the 1996, 1997, and 1998 epidemics. Antibody prevalence and reported case incidence in different health districts were disproportional. The article concludes by recommending further research on the significance of transmission rates during epidemics and more intensive virological surveillance, especially in years with few reported cases. PMID- 17334581 TI - [Cultural aspects in the understanding of chronic periodontitis: a qualitative study]. AB - This study aimed to analyze the concepts, beliefs, attitudes, and explanatory models related to chronic periodontitis among individuals with this disease in order to facilitate communications between dentists and patients and foster conscientious treatment adherence. The study sample consisted of 20 patients from the Periodontics Specialization Courses at Fortaleza University and the Brazilian Dental Association in Fortaleza, Ceara State. Data were gathered from October 2004 to January 2005. A qualitative methodological framework was used to interpret the patients' subjective expression. Semi-structured interviews were applied to obtain patients' accounts of their individual experience with the disease condition. Thematic discourse analysis used: empirical categories established within the study itself, simple frequencies and calculated percentages, and refinement of thematic classifications. According to their reports, patients understand the periodontal heath-disease process through the intermediation of both popular and scientific knowledge, involvement of living and work conditions, and access to quality care, i.e., they do not incorporate only the biomedical discourse. PMID- 17334582 TI - [Depression and clinical illness: comorbidity in a geriatric outpatient clinic]. AB - The aim of this study was to investigate the association between depression and clinical illness among a group of elderly in the city of Salvador, Bahia, Brazil. The study population included 1,120 individuals over 60 years of age treated at a geriatric outpatient clinic. Crude and stratified prevalence ratios were calculated. Data were stratified by gender, age, and nutritional status. Ninety five percent of the sample presented at least one chronic disease, the most frequent being hypertension (62.2%), osteoarthritis (40%), and urinary incontinence (35%). Depression was diagnosed in 23.4%, more commonly among women (PR = 1.28; 95%CI: 0.99-1.65) and those under 75 years (PR = 1.24; 95%CI: 1.00 1.53). There was an association between number of chronic diseases (> 3) and depression (PR = 1.31; 95%CI: 1.04-1.66). Parkinson's disease was associated with depression, more evident among females (PR = 1.59; 95%CI: 1.05-2.41) and in the 70-79-year age group (PR = 2.02; 95%CI: 1.28-3.20). The study demonstrates an association between depression and chronic comorbidity. Since many elderly present multiple chronic diseases, health professionals should be alert to the possibility of depressive symptoms in these patients. PMID- 17334583 TI - [Evaluation of quality of epidemiological and demographic variables in the Live Births Information System, 2002]. AB - This study evaluates the quality of data in the Brazilian Live Births Information System (SINASC), focusing on the methodological clarity of documentation and adequate data completeness and consistency at the national, regional, and State levels in 2002. The variables analyzed were: skin color/race of newborn, maternal schooling, maternal marital status, maternal occupation, maternal age, prenatal visits, live births, stillbirths, and birth weight. For most of the variables, SINASC shows good data completeness and consistency, but there were serious problems with the quality of data on previous children and maternal occupation. Related to race, there were some methodological problems in the definition and incomplete filling-in for the Federal District (Brasilia) and the States of Sao Paulo, Bahia, and Sergipe. Statistical analysis confirmed a significant association between data completeness and indicators of poverty and inequality. The study showed that improvements in SINASC data quality could make this system a good epidemiological source for identifying risk factors and socioeconomic conditioning factors. PMID- 17334584 TI - [Secular plague trend in Ceara State, Brazil]. AB - After its introduction into the State of Ceara, Brazil, in 1900, the plague was established in seven ecological complexes: Chapada do Araripe and the Ibiapaba, Baturite, Machado, Matas, Pedra Branca, and Uruburetama mountains. These natural foci were monitored successively from 1935 to 2004 by the National Health Department, National Plague Service, National Department of Rural Endemics, Superintendency of Public Health Campaigns, National Health Foundation, and finally by the National Health Surveillance Secretariat. Data analysis on human cases during these 70 years allowing identifying different plague circulation patterns in the human population, alternating high incidence with silent periods and characterizing a chronological periodicity with unique epidemiological characteristics, besides concluding that plague should still be considered a potential threat, thus justifying the revitalization of surveillance measures by strengthening all levels in the Unified National Health System. PMID- 17334585 TI - Data on sand fly fauna (Diptera, Psychodidae, Phlebotominae) in Itatiaia National Park, Rio de Janeiro State, Brazil. AB - The sand fly fauna in Itatiaia National Park, Rio de Janeiro, Brazil, was investigated in different habitats ranging from sylvatic areas to those altered by human activity related to ecotourism, specifically identifying species that have been suggested as potential leishmaniasis vectors. Sand flies were captured from June 2002 to March 2004, using CDC light traps and Shannon traps. A total of 1,256 sand fly specimens were captured, from species belonging to genera Lutzomyia and Brumptomyia: Brumptomyia guimaraesi, B. troglodytes, Lutzomyia (Lutzomyia) amarali, L. lanei, L. migonei, L. sallesi, L. edwardsi, L. tupynambai, L. (Pintomyia) pessoai, L. (P.) bianchigalatie, L. rupicola, L. (Psathyromyia) shannoni, L. pascalei, L. (Psychodopygus) matosi, L. (P.) davisi, L. (P.) hirsuta hirsuta, L. (P.) ayrozai, L. peresi, L. monticola, and L. misionensis. Worthy of special attention were four species that are considered potential vectors for cutaneous leishmaniasis in Brazil: L. ayrozai, L. hirsuta hirsuta, L. migonei, and L. davisi, representing 19.19% of the specimens captured in this study. PMID- 17334586 TI - Phenotypic heterogeneity of mutations in androgen receptor gene. AB - Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens. PMID- 17334587 TI - Expression of human AR cDNA driven by its own promoter results in mild promotion, but not suppression, of growth in human prostate cancer PC-3 cells. AB - AIM: To examine the physiological role of the androgen receptor (AR) in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. METHODS: We generated an AR-expressing PC-3(AR)9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3(AR)2 (stable clone that expresses AR under the control of the cytomegalovirus (CMV) promoter, established by Heisler et al.) after androgen treatment. RESULTS: We found that dihydrotestosterone (DHT) from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3(AR)2 compared with its vector control, PC-3(pIRES). In contrast, PC-3(AR)9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT. CONCLUSION: These data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer (AIPC) PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3(AR)9 prostate cancer cells. PMID- 17334588 TI - Expression and localization of CKLFSF2 in human spermatogenesis. AB - AIM: To investigate the expression and subcellular localization of chemokine-like factor superfamily 2 (CKLFSF2) in human testis and its potential role in spermatogenesis. METHODS: A specific polyclonal antibody against CKLFSF2 was raised. The expression and cellular localization of CKLFSF2 in the seminiferous tubules was checked by immunohistochemistry method. Also, in situ hybridization was applied to localize the mRNA distribution. The EGFP-CKLFSF2 fusion protein was expressed in COS-7 cells to localize its subcellular location in vitro. In addition, the abnormal expression of CKLFSF2 in testes of patients with male infertility was assayed by reverse transcription polymerase chain reaction (RT PCR) and immunohistochemistry methods. RESULTS: Having a close correlation with spermatogenesis defects, CKLFSF2 was specifically expressed in meiotic and post meiotic germ cells, which were localized to the endoplasmic reticulum (ER) near the Golgi apparatus. CONCLUSION: CKLFSF2 could play important roles in the process of meiosis and spermiogenesis, and might be involved in the vesicular transport or membrane apposition events in the endoplasmic reticulum. PMID- 17334589 TI - Reduced expression of alpha-tocopherol-associated protein is associated with tumor cell proliferation and the increased risk of prostate cancer recurrence. AB - AIM: To examine the impact and prognostic significance of alpha-tocopherol associated protein (TAP) expression in a series of prostate cancer patients. METHODS: Tissues from 87 patients underwent radical prostatectomy were examined for TAP expression by immunohistochemistry. The relationships of the staining results, the clinic pathological characteristics and the recurrence times were analyzed. RESULTS: Compared with the adjacent areas of normal and benign glands, immunoreactivity of TAP was reduced in areas of prostate cancer. A lower TAP positive cell number per mm(2) of the largest cancer area (defined as TAP-PN) was associated with higher clinical stage (r = -0.248, P = 0.0322). Inverse associations were found among the TAP-PN and positive lymph nodes (r = -0.231, P = 0.0325), preoperative prostate-specific antigen (PSA) levels (r = -0.423, P = 0.0043), tumor size (r= -0.315, P= 0.0210) and elevated tumor cell proliferation, which was indicated by the staining of Ki-67 (r = -0.308, P = 0.0026). TAP-PN was a significant predictor of recurrence univariately (P = 0.0006), as well as multivariately, adjusted for known markers including preoperative PSA, clinical stage, Gleason score, surgical margin, extra-prostatic extension, seminal vesicle invasion and lymph node metastasis (P = 0.0012). CONCLUSION: Reduced expression of TAP was associated with the cell proliferation status of prostate cancer, adverse pathological parameters and the increased risk of recurrence. PMID- 17334590 TI - Biophysical mechanism-mediated time-dependent effect on sperm of human and monkey vas implanted polyelectrolyte contraceptive. AB - AIM: To determine the short and long-term morphological effects on sperm as induced by intra-vas alteration of pH and electrical charge. METHODS: Desired biophysical influences were obtained by injection of reversible inhibition of sperm under guidance (RISUG) into the lumen of the vas deferens of human subjects and the monkey. RISUG is a polyelectrolyte hydrogel complex of styrene maleic anhydride (SMA) and dimethyl sulfoxide (DMSO) which generates an electrostatic charge and also lowers in a near space of pH domain. The morphology of sperm was examined by light microscopy, scanning and transmission electron microscopy. Human study enabled semen collection by masturbation as early as 3 h after injection and studies extended up to 6 months. In the monkey, on vas excision after RISUG implantation, sperm characteristics were examined in serial sections. RESULTS: Semenology in clinical studies and histological data of the monkey showed a time-sequenced sperm plasma membrane, tail mitochondria and nuclear decondensation alterations in sperm structural components, which beared marked similarity to changes in the sperm head and tail during capacitation and entry into the ovum. CONCLUSION: The findings provide a means of causing such changes in the sperm that inhibit the fertilizing ability before the nucleus is affected. Therefore achieving non-obstructive vas-based contraception, without genotoxic or teratogenic effects caused by infertile sperm passing into the semen, is feasible. PMID- 17334591 TI - Effect of two different extracts of red maca in male rats with testosterone induced prostatic hyperplasia. AB - AIM: To determine the effect of two different extracts of red maca in male rats. METHODS: Prostatic hyperplasia was induced in male rats with testosterone enanthate (TE). The study comprised six groups: one control group (group 1), one group treated with TE (group 2), two groups treated with TE and aqueous extract of red maca (groups 3 and 4), one group treated with hydroalcoholic extract of red maca (group 5) and one group treated with finasteride (0.1 mg, group 6). Differences in the aqueous extract dependent on the length of time of boiling, whether for 2 or 3 hours, for groups 3 and 4 was assessed. Extracts of red maca contained 0.1 mg of benzylglucosinolate. Thereafter, a dose-response effect of different doses of benzylglucosinolates (0.02-0.08 mg) in red maca extracts was assessed. RESULTS: Prostate weight was similar in rats treated with freeze-dried aqueous extract of red maca prepared after 2 and 3 hours of boiling. Freeze-dried aqueous extract of red maca, hydroalcoholic extract of red maca and finasteride reduced prostate weight in rats with prostatic hyperplasia. No difference was observed between the data obtained from aqueous extract or hydroalcoholic extract of red maca. A dose dependent reduction of prostate weight was observed with the increase of the dose of benzylglucosinolates in red maca extracts. CONCLUSION: The present study showed that hydroalcoholic or aqueous extract of red maca containing 0.1 mg of benzylglucosinolate can reduce prostate size in male rats in which prostatic hyperplasia had been induced by TE. PMID- 17334592 TI - Long-term effectiveness of luteinizing hormone-releasing hormone agonist or antiandrogen monotherapy in elderly men with localized prostate cancer (T1-2): a retrospective study. AB - AIM: To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat patients with localized prostate cancer (T1-2) at our institution. METHODS: Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer (T1-2) received either LHRH agonist (leuprolide acetate 7.5 mg/month) monotherapy (group 1, n = 62) or antiandrogen monotherapy (group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d. and 4 received flutamide 250 mg t.i.d.). The mean age in both groups was 76 years. RESULTS: The mean follow-up time was (50.8 +/- 8.5) months in group 1 and (43.1 +/- 2.2) months in group 2. Prostate-specific antigen (PSA) levels rose in only 1 of the 62 patients (1.6%) in group 1, and in 20 of the 35 patients (57.1%) in group 2. In group 2, 10 of the 20 patients (50%) with increasing PSA levels were treated with LHRH salvage therapy, and eight (80%) responded. Hot flashes (54.8%) and lethargy (41.9%) were the most common side effects in group 1. In contrast, nipple-tenderness (40%) and light-dark adaptation (17.1%) were more often seen in group 2. Only 1 of the 62 patients (1.6%) in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients (22.9%) in group 2 did so. CONCLUSION: Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer (T1-2). It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size. PMID- 17334593 TI - Sildenafil versus continuous positive airway pressure for erectile dysfunction in men with obstructive sleep apnea: a comparative study of their efficacy and safety and the patient's satisfaction with treatment. AB - AIM: To assess the efficacy of sildenafil and continuous positive airway pressure (CPAP) in the treatment of concurrent erectile dysfunction (ED) with obstructive sleep apnea (OSA), and to gauge the level of treatment satisfaction in patients and their partners. METHODS: Forty men were treated for 12 weeks with sildenafil 100 mg (20 men) or CPAP during nighttime sleep (20 men). Treatment efficacy was assessed by the rate of successful intercourse attempts, and satisfaction with treatment was assessed by patients' and partners' answers to question 1 of the Erectile Dysfunction Inventory of Treatment Satisfaction. RESULTS: Under sildenafil, 128 of 249 (51.4%) intercourse attempts were successful; under CPAP, 51 of 193 (26.9%) attempts were successful ((c)P < 0.001). Erectile function was improved in both groups. After sildenafil and CPAP treatment, the mean International Index for Erectile Function domain scores were 14.3 and 10.8, respectively ((b)P = 0.025), compared to 7.8 and 7 at baseline, respectively. CPAP and sildenafil were well tolerated. Sporadic episodes of nasal dryness under CPAP and transient headache and flushing under sildenafil were not significant. Fifty percent of patients treated with sildenafil and 25% with CPAP were satisfied with the treatment, and their partners were equally satisfied. The satisfaction scores for both patients and partners under sildenafil were superior to those under CPAP ((c)P < 0.002). CONCLUSION: Both sildenafil 100 mg and CPAP, used separately, had positive therapeutic impact but sildenafil was superior. Patients and their partners were more satisfied with sildenafil for the treatment of ED. However, because of the high proportion of dissatisfied men and partners, new therapeutic agents or a combination of the two methods must be studied further. PMID- 17334594 TI - Seminal plasma anti-Mullerian hormone level correlates with semen parameters but does not predict success of testicular sperm extraction (TESE). AB - AIM: To assess seminal plasma anti-Mullerian hormone (AMH) level relationships in fertile and infertile males. METHODS: Eighty-four male cases were studied and divided into four groups: fertile normozoospermia (n = 16), oligoasthenoteratozoospermia (n = 15), obstructive azoospermia (OA) (n = 13) and non-obstructive azoospermia (NOA) (n = 40). Conventional semen analysis was done for all cases. Testicular biopsy was done with histopathology and fresh tissue examination for testicular sperm extraction (TESE) in NOA cases. NOA group was subdivided according to TESE results into unsuccessful TESE (n = 19) and successful TESE (n = 21). Seminal plasma AMH was estimated by enzyme linked immunosorbent assay (ELISA) and serum follicular stimulating hormone (FSH) was estimated in NOA cases only by radioimmunoassay (RIA). RESULTS: Mean seminal AMH was significantly higher in fertile group than in oligoasthenoteratozoospermia with significance (41.5 +/- 10.9 pmol/L vs. 30.5 +/- 10.3 pmol/L, P < 0.05). Seminal AMH was not detected in any OA patients. Seminal AMH was correlated positively with testicular volume (r = 0.329, P = 0.005), sperm count (r = 0.483, P = 0.007), sperm motility percent (r = 0.419, P = 0.021) and negatively with sperm abnormal forms percent (r = -0.413, P = 0.023). Nonsignificant correlation was evident with age (r = -0.155, P = 0.414) and plasma FSH (r = -0.014, P = 0.943). In NOA cases, seminal AMH was detectable in 23/40 cases, 14 of them were successful TESE (57.5%) and was undetectable in 17/40 cases, 10 of them were unsuccessful TESE (58.2%). CONCLUSION: Seminal plasma AMH is an absolute testicular marker being absent in all OA cases. However, seminal AMH has a poor predictability for successful testicular sperm retrieval in NOA cases. PMID- 17334595 TI - Surgical treatment of a rare case of penile squamous cell carcinoma in a 65-year old man. AB - Penile squamous cell carcinoma has been commonly reported in the past decades. We describe a rare case of a huge squamous cell carcinoma of the penis in a 65-year old patient with a 4-year history of tumor growth, for which total penectomy, perineal urethrostomy and bilateral inguinal lymphadenectomy were carried out. We suggest that aggressive surgical intervention should be recommended for those with well-differentiated penile carcinoma regardless of the size of the tumor. PMID- 17334596 TI - Extragastrointestinal stromal tumor presenting as a scrotal mass: an unusual case. AB - We describe an unusual case of extragastrointestinal stromal tumor (EGIST) presenting as a scrotal mass. A 71-year-old man presented with a gradually enlarging scrotal mass with a 20-year duration. Physical examination revealed a huge (as large as volleyball), round, nontender mass occupying the whole scrotum, which was resected completely. Clinical and radiological findings did not comply with any other primary site disease. Under histological examination, the tumor showed a spindle cell pattern with low cellularity, absence of necrotic and mitotic features. immunohistochemical analysis revealed the tumor reactive for CD117 and CD34, while negative for smooth muscle actin, desmin and S-100 protein. To our knowledge, this is the first reported case of an EGIST involving the scrotum. PMID- 17334597 TI - Analysis of the CAG repeat number in exon 1 of the androgen receptor gene in Slovene men with idiopathic azoospermia and oligoasthenoteratozoospermia. PMID- 17334598 TI - Subjective outcome evaluation of the project P.A.T.H.S.: findings based on the perspective of the program participants. AB - A total of 52 schools (n = 8679 students) participated in the experimental implementation phase of the project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes). After completion of the Tier 1 Program, students were invited to respond to the Subjective Outcome Evaluation Form (Form A) to assess their views of the program, instructors, and perceived effectiveness of the program. Based on the consolidated reports submitted by the schools to the funding body, the research team aggregated the consolidated data to form a "reconstructed" overall profile on the perceptions of the program participants. Results showed that high proportions of the respondents had positive perceptions of the program and the instructors, and roughly four-fifths of the respondents regarded the program as helpful to them. The present study provides additional support for the effectiveness of the Tier 1 Program of the P.A.T.H.S. Project in Hong Kong. PMID- 17334599 TI - The role of 5-lipoxygenase and leukotrienes in shock and ischemia-reperfusion injury. AB - The leukotrienes (LTs) are metabolic products of arachidonic acid via the 5 lipoxygenase (5-LO) pathway. The biological activities of LTs suggest that they are mediators of acute inflammatory and immediate hypersensitivity responses. In particular, the 5-LO activation has been proposed to be an important regulator for pathogenesis in multicellular organisms. The role of LTs in tissue damage, associated with septic and nonseptic shock and ischemia-reperfusion, has been extensively studied by the use of 5-LO inhibitors, receptor antagonists, and mice with a targeted disruption of the 5-LO gene (5-LOKO). In particular, several data indicate that LTs regulate neutrophil trafficking in damaged tissue in shock and ischemia-reperfusion, mainly through the modulation of adhesion molecule expression. This concept may provide new insights into the interpretation of the protective effect of 5-LO inhibition, which may be useful in the therapy of pathological conditions associated with septic and nonseptic shock and ischemia reperfusion injury. PMID- 17334600 TI - Intestinal ileus as a possible cause of hypobicarbonatemia. AB - The possible occurrence of metabolic acidosis in patients with intestinal ileus is not well recognized. We describe a patient with acute alcohol-induced pancreatitis and a large transverse colon ileus in which plasma bicarbonate dropped rapidly in the absence of an increase in the plasma anion gap. The urinary anion gap and ammonium excretion were consistent with an appropriate renal response to metabolic acidosis and against the possibility of respiratory alkalosis. The cause of the falling plasma bicarbonate was ascribed to intestinal bicarbonate sequestration owing to the enhancement of chloride-bicarbonate exchange in a dilated paralyzed colon. PMID- 17334601 TI - Multiple cysts in the kidney and lungs in a patient with polycystic kidney disease and lymphangioleiomyomatosis. PMID- 17334602 TI - Involvement of the Gli3 (extra-toes) gene region in body weight in mice. AB - The mutation extra-toes (Gli3Xt-J) on chromosome (Chr) 13 of the mouse is known to be involved in the development of the skeleton. The only visible manifestation is the presence of an extra digit on each hind foot. Here we report evidence from several experiments that Gli3XtJ/+ mice weigh more than littermate Gli3+/+ mice, suggesting an effect on body weight of Gli3 or of a gene tightly linked to it on Chr 13. Four independent experiments in different environments were conducted on mice with different genetic backgrounds derived from the C3XtEso Gli3Xt-J/+ Eso/+ linkage testing strain and the JE/Le strain at adult age. The analyses have shown an association between the Gli3Xt-J allele and a body weight increase of about 6.5%. This effect is genetically dominant. It would appear that if the gene of interest is not Gli3 itself, it must be very close to this locus. Indeed, the expected size for this fragment is 7.9 +/- 5.3 cM. The manifestation of this gene, observed in two animal facilities and on different genetic backgrounds, is consistent with the idea that the effect of the gene(s) is displayed in a stable manner. It accounts for a variation of 6.5% of body weight. PMID- 17334603 TI - Optical coherence tomography. AB - Optical coherence tomography (OCT) is an optical imaging modality that performs high-resolution, cross-sectional, subsurface tomographic imaging of the microstructure of tissues. The physical principle of OCT is similar to that of B mode ultrasound imaging, except that it uses infrared light waves rather than acoustic waves. The in vivo resolution is 10-25 times better (about 10 microm) than with high-frequency ultrasound imaging, but the depth of penetration is limited to 1-3 mm, depending on tissue structure, depth of focus of the probe used, and pressure applied to the tissue surface. In the last decade, OCT technology has evolved from an experimental laboratory tool to a new diagnostic imaging modality with a wide spectrum of clinical applications in medical practice, including the gastrointestinal tract and pancreatico-biliary ductal system. OCT imaging from the gastrointestinal tract can be done in humans by using narrow-diameter, catheter-based probes that can be inserted through the accessory channel of either a conventional front-view endoscope, for investigating the epithelial structure of the gastrointestinal tract, or a side view endoscope, inside a standard transparent ERCP (endoscopic retrograde cholangiopancreatography) catheter, for investigating the pancreatico-biliary ductal system. The esophagus and esophagogastric junction have been the most widely investigated organs so far; more recently, duodenum, colon, and the pancreatico-biliary ductal system have also been extensively investigated. OCT imaging of the gastrointestinal wall structure is characterized by a multiple layer architecture that permits an accurate evaluation of the mucosa, lamina propria, muscularis mucosae, and part of the submucosa. The technique may therefore be used to identify preneoplastic conditions of the gastrointestinal tract, such as Barrett's epithelium and dysplasia, and evaluate the depth of penetration of early-stage neoplastic lesions. OCT imaging of the pancreatic and biliary ductal system could improve the diagnostic accuracy for ductal epithelial changes, and the differential diagnosis between neoplastic and non-neoplastic lesions. PMID- 17334604 TI - Manual therapy: the historical, current, and future role in the treatment of pain. AB - Manual therapy has been an approach in the management of patients with various disorders dating back to ancient times and continues to play a significant role in current health care. The future role of manual therapy in health care is an important area of research. This paper reviews the history of manual therapy, examines the current literature related to the use of manual techniques (including manipulation, massage, and nerve manipulation), and discusses future research topics. The literature related to manual therapy has historically been anecdotal and theoretical, and current research tends to have a generic approach with broad definitions of manual therapy and inconsistencies in the classification of specific disorders. Systematic reviews of various types of manual therapy have differed on their conclusions regarding the effectiveness of this treatment modality. The current demand in health care for evidence-based practice necessitates a movement towards more specificity in the research of the effectiveness of manual therapy, with emphasis on specific patient signs and symptoms and specific manual techniques that result in effective care. PMID- 17334605 TI - Targeting polymorphonuclear leukocytes in acute myocardial infarction. AB - Several studies have recognized the strong impact that the acute myocardial infarctions (AMI) have on the morbidity and mortality of patients affected by cardiovascular diseases. Still open, however, is the field concerning the mediators and the pathways involved in the etiology of this cardiovascular event. The present review would support the relatively new discovered role that the polymorphonuclear leukocytes (PMNs) have in the pathogenesis of the AMI, through a brief analysis of past and ongoing research. Particularly, it is reviewed here the possibility that inhibition of the activity of PMNs and inhibition of the signaling pathways related to their activity may result useful in AMI and may improve the prognosis of this pathology. This review, indeed, presents and discusses new data on one of the lipid kinase, the phosphoinositide 3-kinase gamma (PI3Kg), and its role in neutrophil recruitment during AMI. PMID- 17334606 TI - Neurodegeneration in schizophrenia: evidence from in vivo neuroimaging studies. AB - Although schizophrenia is primarily considered to be a neurodevelopmental disorder, there is a growing consensus that the disorder may also involve neurodegeneration. Recent research using non-invasive neuroimaging techniques, such as magnetic resonance imaging, suggests that some patients with schizophrenia show progressive losses of gray matter in the frontal and temporal lobes of the brain. The cellular mechanisms responsible for such gray matter losses are unknown, but have been hypothesized to involve abnormal increases in apoptosis. PMID- 17334607 TI - F-waves--physiology and clinical uses. AB - F-waves are low amplitude responses produced by antidromic activation of motoneurons. They may not appear after each stimulus and are inherently variable in latency, amplitude, and configuration. Meaningful analysis of F-waves requires an appreciation of these characteristics of F-waves as well as an understanding of their physiology. These features of F-waves as well as their physiology are reviewed. This is important since F-waves are one of the most frequently used studies in clinical neurophysiology and much of the controversies surrounding the use of F-waves relates to a failure to adequately consider the requirements of F wave analysis. These requirements include the number of F-waves that need to be recorded, the parameters that should be evaluated, and the muscle from which the F-waves are recorded. If analyzed correctly, current reports would indicate that F-waves are the most sensitive and reliable nerve conduction study for evaluating polyneuropathies, can be abnormal in focal proximal nerve dysfunction, can be at least as sensitive as needle electromyography for defining lumbosacral radiculopathies, and can provide a meaningful physiological window into disorders of the central nervous system. Reports supporting these statements and their clinical relevance are discussed. PMID- 17334608 TI - Evaluating the role of Wnt signal transduction in promoting the development of the heart. AB - Wnts are a family of secreted signaling proteins that are encoded by 19 distinct genes in the vertebrate genome. These molecules initiate several signal transduction pathways: the canonical Wnt, Wnt/Ca2+, and Wnt/planar cell polarity pathways. Wnt proteins have major impact on embryonic development, tumor progression, and stem cell differentiation. Wnt signal transduction also influences the formation of the heart, yet many issues concerning the involvement of Wnt regulation in initiating cardiac development remain unresolved. In this review, we will examine the published record to discern (a) what has been shown by experimental studies on the participation of Wnt signaling in cardiogenesis, and (b) what are the important questions that need to be addressed to understand the importance and function of Wnt signal transduction in facilitating the development of the heart. PMID- 17334609 TI - Physician satisfaction in a cancer prevention program for low-income women in Nevada. AB - Physicians and health care organizations that provide services to low-income patients are valuable partners in improving health care access for the uninsured and medically underserved. In this pilot study, we explored physicians' needs and factors for satisfaction in the Women's Health Connection (WHC), a breast and cervical cancer-screening program for low-income women in Nevada. Of the 126 physicians in the WHC program, 50 physicians completed a needs-and-satisfaction questionnaire. Survey data were subjected to factor analysis using Varimax rotation. The results yielded three components, which accounted for 65% of the variance. The three components or dimensions for physician satisfaction were: (1) appropriate administrative support and documentation, (2) availability of support for medical management, and (3) timeliness of diagnostic reports. Amount of reimbursement was not a significant factor. The respondents serving in this cancer prevention program for low-income women were satisfied in their involvement in the program. Further attention should be given on the identified issues for satisfaction among physicians, which could lead to quality improvement and serve as a model for other programs that serve low-income patients in cancer prevention. PMID- 17334610 TI - Teenage pregnancy: impact of the integral attention given to the pregnant teenager and adolescent mother as a protective factor for repeat pregnancy. AB - The purpose of this study was to evaluate the impact of the integral attention to the health of pregnant adolescents and adolescent mothers, having follow-up from the Integral Support Program for the Pregnant Teen (ISPPT), with the intention to determine quality of life and prevent repeat pregnancy. A prospective study comprised 85 adolescents attended by the ISPPT between January 2002 and June 2006 who participated in meetings during pregnancy with a multidisciplinary team that provided orientation concerning family planning, self-esteem, pregnancy prevention, motivation to continue education and/or work, and evaluate the postpartum mother-child relationship. The following were analyzed: education level, marital status, contraceptive use, thoughts and attempts at abortion, repeat pregnancy. This study was approved by the Human Research Ethics Committee. The Epi-Info v6.0b software was used for data and result evaluation using the means and the chi-squared test. The mean age of the adolescents was 15.7 years, 3.52% had repeat pregnancy within a mean follow-up of 23 months after childbirth, the mean education level was 8.1 years, 30.5% dropped out of school, with 79.4% occurring before pregnancy, 64.6% used no contraceptives, 68.3% were single, and 81.3% had a positive role model. One year after birth, 67.5% studied, 50% worked, 55.1% lived with the partner, 77% correctly used contraceptives, every child lived with their mothers and their vaccinations were up to date. The results demonstrate that the global attention given to the health of adolescent mothers and pregnant adolescents is a protective factor for pregnancy relapse and quality of life. PMID- 17334611 TI - Subjective outcome evaluation of the project P.A.T.H.S.: findings based on the perspective of the program implementers. AB - A total of 52 schools (n = 8679 students) participated in the experimental implementation phase of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes). After completion of the Tier 1 Program, 344 instructors completed the Subjective Outcome Evaluation Form (Form B) to assess their views of the program, instructors, and perceived effectiveness of the program. Based on the consolidated reports submitted by the schools to the funding body, the research team aggregated the consolidated data to form a "reconstructed" overall profile on the perceptions of the program implementers. Results showed that high proportions of the workers had positive perceptions of the program and their own performance, and roughly 90% of the workers regarded the program as helpful to the program participants. The present study provides additional support for the effectiveness of the Tier 1 Program of the P.A.T.H.S. Project in Hong Kong. PMID- 17334612 TI - From the behavioral pharmacology of beta-carbolines to seizures, anxiety, and memory. AB - A number of beta-carbolines are inverse agonists of the GABA-A receptor complex, acting on the benzodiazepine site. They show convulsive properties when administered at high doses, anxiogenic properties at moderate doses, and learning enhancing effects at low doses. These data suggest a possible physiological relationship, through the GABA-A receptor channel, between memory processes, anxiety, and ultimately, in pathological states, epileptic seizures. This relationship seems to be confirmed partially by experiments on mouse strains selected for their resistance (BR) and sensitivity (BS) to a single convulsive dose of a beta-carboline. These two strains also show differences in anxiety and learning abilities. However, some opposite results found while observing the behavior of the two strains suggest that in addition to pharmacologically induced anxiety, there is spontaneous anxiety, no doubt involving other brain mechanisms. PMID- 17334613 TI - Chemokines. AB - Chemokines are a family of polypeptides that direct the migration of leukocytes toward a site of infection. They play a major role in autoimmune disease and chemokine receptors have recently been found to mediate HIV-1 fusion. In this short review we examine the role of chemokines in host defence and in the pathophysiology of autoimmune diseases. We conclude by discussing various therapeutic approaches that target chemokine receptors and that could be beneficial in disease. PMID- 17334614 TI - Galactosaminoglycan function and oligosaccharide structure determination. AB - This review will discuss the importance of sequencing long chondroitin sulfate and dermatan sulfate chains specifically derived from decorin. Decorin is a member of the small leucine-rich repeat proteoglycans and ubiquitously expressed primarily in the skin. Sequence information and diverse function of glycosaminoglycans is further influenced by variable expression through the core protein indicating the importance to analyse glycosaminoglycans from specific proteoglycans. PMID- 17334615 TI - Preanesthetic evaluation and assessment of children with Down's syndrome. AB - During preoperative evaluation for anesthesia in the Down patient, it is important to focus attention on the functional conditions of the patient and systems that frequently show anomalies. One of the challenges of evaluating pre operative conditions and potential risks in the Down patient is the lack of a gold-standard evaluation score; cervical spine abnormalities, reduced dimensions and malformations of the airways, neurological changes, respiratory and cardiac disease, as well as endocrinological and metabolic alterations. We suggest, as a possible method of evaluation for patients with mental retardation and possible malformations, a new scale which takes the functional and mental conditions into account: the Sensorial, Psychological, Anatomical, Biological, Operational and Surgical (SPABOS) Compliance Score. PMID- 17334616 TI - Fetus in fetu--a mystery in medicine. AB - Fetus in Fetu (FIF) is a rare condition where a monozygotic diamnionic parasitic twin is incorporated into the body of its fellow twin and grows inside it. FIF is differentiated from teratoma by the presence of vertebral column. An eight year old girl presented with an abdominal swelling which by X-ray, ultrasonography and CT scan revealed a fetiform mass containing long bones and vertebral bodies surrounded by soft tissue situated on right lumber region. On laparotomy, a retroperitoneal mass resembling a fetus of 585 gm was removed. It had a trunk and four limbs with fingers and toes, umbilical stump, intestinal loops and abundant scalp hairs but was devoid of brain and heart. Histology showed various well differentiated tissues in respective sites. FIF is a mystery in reproduction and it is scarce in literature in such well-developed stage. PMID- 17334617 TI - Convergence of subjective outcome and objective outcome evaluation findings: insights based on the project P.A.T.H.S. AB - A total of 546 students participated in the Tier 1 Program of the P.A.T.H.S. Project responded to the Chinese Positive Youth Development Scale (CPYDS) at pretest and posttest and the Subjective Outcome Scale (SOS) at posttest. Result showed that the SOS was internally consistent. The SOS total scores were significantly related to measures of global satisfaction and the participants' degree of sharing with others, thus giving support to its construct validity. Factor analysis revealed that there were three dimensions of the scale and the related subscales were significantly correlated among themselves. Based on the significant relationships between the SOS measures of perceived program effectiveness and posttest CPYDS scores as well as changes in CPYDS scores, the present study revealed the convergence of subjective outcome evaluation findings and objective outcome evaluation findings in the P.A.T.H.S. Project. PMID- 17334618 TI - Class B gene expression and the modified ABC model in nongrass monocots. AB - The discovery of the MADS-box genes and the study of model plants such as Arabidopsis thaliana and Antirrhinum majus have greatly improved our understanding of the molecular mechanisms driving the diversity in floral development. The class B genes, which belong to the MADS-box gene family, are important regulators of the development of petals and stamens in flowering plants. Many nongrass monocot flowers have two whorls of petaloid organs, which are called tepals. To explain this floral morphology, the modified ABC model was proposed. This model was exemplified by the tulip, in which expansion and restriction of class B gene expression is linked to the transition of floral morphologies in whorl 1. The expression patterns of class B genes from many monocot species nicely fit this model; however, those from some species, such as asparagus, do not. In this review, we summarize the relationship between class B gene expression and floral morphology in nongrass monocots, such as Liliales (Liliaceae) and Asparagales species, and discuss the applicability of the modified ABC model to monocot flowers. PMID- 17334619 TI - A role for the cytoskeleton in heart looping. AB - Over the past 10 years, key genes involved in specification of left-right laterality pathways in the embryo have been defined. The read-out for misexpression of laterality genes is usually the direction of heart looping. The question of how dextral looping direction occurred mechanistically and how the heart tube bends remains unknown. It is becoming clear from our experiments and those of others that left-right differences in cell proliferation in the second heart field (anterior heart field) drives the dextral direction. Evidence is accumulating that the cytoskeleton is at the center of laterality, and the bending and rotational forces associated with heart looping. If laterality pathways are modulated upstream, the cytoskeleton, including nonmuscle myosin II (NMHC-II), is altered downstream within the cardiomyocytes, leading to looping abnormalities. The cytoskeleton is associated with important mechanosensing and signaling pathways in cell biology and development. The initiation of blood flow during the looping period and the inherent stresses associated with increasing volumes of blood flowing into the heart may help to potentiate the process. In recent years, the steps involved in this central and complex process of heart development that is the basis of numerous congenital heart defects are being unraveled. PMID- 17334620 TI - Self-reported low self-esteem. Intervention and follow-up in a clinical setting. AB - At the Research Clinic for Holistic Medicine in Copenhagen, 43 patients who presented with low or very low self-esteem were treated with psychodynamic short term therapy complemented with bodywork. They received an average of 20 sessions at a cost of 1,600 EURO. The bodywork helped the patients to confront old emotional pain from childhood trauma repressed to the body-mind. Results showed that 60.5% recovered from low self-esteem (95% CI: 44.41-75.02%). Calculated from this, we have NNT = 1.33-2.25. Almost all aspects of life improved at the same time (p < 0.01): physical health, mental health, quality of life, and ability to function in a number of important areas (partner, friends, sexually, and socially). This indicated that we had successfully induced existential healing (Antonovsky salutogenesis). The strategy of improving self-esteem can be the key to a new life for patients presenting with low quality of life, poor health (physical and/or mental), and poor ability to function. The patients were strongly motivated and willing to endure strong emotional pain provoked by the therapy. The rate of recovery is comparable to the most successful interventions with psychological and psychiatric treatment. Clinical holistic treatment has many advantages: efficiency, low cost, lack of negative side effects, lasting results, lack of use of psychopharmacological drugs (often with side effects), and an important preventive dimension. PMID- 17334621 TI - Clinical holistic medicine (mindful, short-term psychodynamic psychotherapy complemented with bodywork) in the treatment of experienced mental illness. AB - Short-term psychodynamic psychotherapy (STPP) complemented with bodywork improved 31 of 54 patients (57.4%, 95% CI: 43.21-70.77%) who rated themselves mentally ill before treatment. Calculated from this we find 1.41 < NNT < 2.31; we estimate NNH > 500. Of the 54 patients, 40% had already had traditional treatment that did not help them. Bodywork helped the patients to confront repressed painful feelings from childhood and this seemingly accelerated and improved the therapy. The patients received in average 20 sessions over 14 months at a cost of 1600 EURO. For the treatment responders, all measured aspects of life (on a five point Likert Scale) improved significantly, simultaneously, and radically: somatic health (from 2.9 to 2.3), self-esteem/relationship to self (from 3.5 to 2.3), relationship to partner (from 4.7 to 2.9 [no partner was rated as "6"]), relationship to friends (from 2.5 to 2.0), ability to love (from 3.8 to 2.4), self-assessed sexual ability (from 3.5 to 2.4), self-assessed social ability (from 3.2 to 2.1), self-assessed working ability (from 3.3 to 2.4), and self assessed quality of life (from 4.0 to 2.3. Quality of life as measured with QOL5 improved (from 3.6 to 2.3 on a scale from 1 to 5; p < 0.001). This general improvement strongly indicated that the patient had healed existentially, i.e., had experienced what Aaron Antonovsky (1923-1994) called "salutogenesis", defined as the process exactly the opposite of pathogenesis. For the treatment responders, the treatment provided lasting benefits, without the negative side effects of drugs. A lasting, positive effect might also prevent many different types of problems in the future. PMID- 17334622 TI - Clinical holistic medicine (mindful, short-term psychodynamic psychotherapy complemented with bodywork) in the treatment of experienced physical illness and chronic pain. AB - We investigated the treatment effect of psychodynamic short-term therapy complemented with bodywork on patients who presented with physical illness at the Research Clinic for Holistic Medicine in Copenhagen. Psychodynamic short-term therapy was complemented with bodywork (Marion Rosen) to help patients confront old emotional pain from childhood trauma(s). Patients were measured with a five item quality of life and health questionnaire (QOL5), a one-item questionnaire of self-assessed quality of life (QOL1), and four questions on self-rated ability to love and to function sexually, socially, and at work (ability to sustain a full time job). Most of the patients had chronic pain that could not be alleviated with drugs. Results showed that 31 patients with the experience of being severely physically ill (mostly from chronic pain), in spite of having consulted their own general practitioner, entered the study. The holistic approach and body therapy accelerated the therapy dramatically and no significant side effects were detected. After the intervention, 38.7% did not feel ill (1.73 < NNT < 4.58) (p = 0.05). Psychodynamic short-term therapy complemented with bodywork can help patients. When the patients responded to the therapy, the self-assessed mental health, relationship with partner, ability to work, self-assessed quality of life, relationships in general, measured QOL (with the validated questionnaire QOL5), and life's total state (mean of health, QOL and ability) were significantly improved, statistically and clinically. Most importantly, all aspects of life were improved simultaneously, due to induction of Antonovsky salutogenesis. The patients received in average 20 sessions over 14 months at a cost of 1600 EURO. For the treatment responders, the treatment seemingly provided lasting benefits. PMID- 17334623 TI - Clinical holistic medicine (mindful, short-term psychodynamic psychotherapy complemented with bodywork) improves quality of life, health, and ability by induction of Antonovsky-salutogenesis. AB - We had a success rate of treating low, self-assessed, global quality of life (measured by QOL1: How would you assess the quality of your life now?) with clinical holistic medicine of 56.4% (95% CI: 42.3-69.7%) and calculated from this the Number Needed to Treat (NNT) as 1.43-2.36. We found that during treatment, (in average 20 sessions of psychodynamic psychotherapy complemented with bodywork at a cost of 1600 EURO), the patients entered a state of Antonovsky-salutogenesis (holistic, existential healing), which also improved their self-assessed health and general ability one whole step up a 5-point Likert Scale. The treatment responders radically improved their self-assessed physical health (0.6 step), self-assessed mental health (1.6 step), their relation to self (1.2 step), friends (0.3 step), and partner (2.1 step on a 6-step scale), and their ability to love (1.2 step) and work (0.8 step), and to function socially (1.0 step) and sexually (0.8 step). It seems that treatment with clinical holistic medicine is the cure of choice when the patients (1) present the triad of low quality of life, poor self-assessed physical and/or mental health, and poor ability to function; and (2) are willing to suffer during the therapy by confronting and integrating old emotional problems and trauma(s) from the past. For these patients, the treatment provided lasting benefits, without the negative side effects of drugs. A lasting, positive effect might also prevent many different types of problems in the future. The therapy was "mindful" in its focus on existential and spiritual issues. PMID- 17334624 TI - Clinical holistic medicine (mindful, short-term psychodynamic psychotherapy complemented with bodywork) in the treatment of experienced impaired sexual functioning. AB - In this clinical follow-up study, we examined the effect of clinical holistic medicine (psychodynamic short-term therapy complemented with bodywork) on patients with poor self-assessed sexual functioning and found that this problem could be solved in 41.67% of the patients ((95% CI: 27.61-56.7%; 1.75 < NNT < 3.62, p = 0.05). The bodywork was inspired by the Marion Rosen method and helped the patients to confront painful emotions from childhood trauma(s), and thus accelerated and deepened the therapy. The goal of therapy was the healing of the whole life of the patient through Antonovsky-salutogenesis. In this process, rehabilitation of the character and purpose of life of the patient was essential, and assisted the patient to recover his or her sense of coherence (existential coherence). We conclude that clinical holistic medicine is the treatment of choice if the patient is ready to explore and assume responsibility for his or her existence (true self), and willing to struggle emotionally in the therapy to reach this important goal. When the patient heals existentially, quality of life, health, and ability to function in general are improved at the same time. The therapy was "mindful" in its focus on existential and spiritual issues. The patients received in average 14.8 sessions at the cost of 1,188 EURO. PMID- 17334625 TI - Utilization of emergency department services by the Bedouin population in southern Israel. AB - Excessive use of the emergency department (ED) is associated with increased costs and workload in the ED, patients' inconvenience and disruption of the continuity of care. The study's goal was to describe trends in ED utilization among Bedouins living in southern Israel. A retrospective cross-sectional study was conducted in primary care clinics in southern Israel. Patients included Bedouin and Jewish patients insured by Clalit Health Services. Data was retrieved from a central database. The number of visits to the ED and age-adjusted rates of ED visits during 2000-2003 were determined in the Bedouin vs. Jewish population. All visits that ended in hospitalization were excluded. Data was stratified according to patients' residence (semi-nomadic vs. urban Bedouins) and referral origin. Age adjusted rates of ED visits decreased from 42.9/1000 patients/month in 2000 to 38.3/1000 patients/month in 2003. There were more ED visits in the Bedouin as compared to Jewish population (38.3/1000 vs. 21.8/1000 patients/month). The decrease in ED utilization was more prominent among adult semi-nomadic Bedouins (from 60.8/1000 to 40.3/1000 patients/month). The proportion of referrals by the family physician to ED significantly decreased (among urban Bedouins: from 54.3% to 43.2%, p<0.001; among semi-nomadic Bedouins: from 53.9% to 39.9%, p<0.001), while the proportion of self-referrals and referrals from physicians other than the family physician increased. A decrease in ED utilization by the Bedouin population during the last years was demonstrated. Utilization of ED services is still increased as compared to the non-Bedouin population. Interventions to control excessive use of ED services in the Bedouin population are currently underway. PMID- 17334626 TI - Criminal mediation for minors in Israel. AB - Mediation was introduced in Canada in 1974 in order to handle a crime of robbery and vandalization committed by adolescents. After mediation, these adolescents agreed to apologize to each of their victims and pay restitution. Several countries (Canada, England, Finland, and the U.S.) have now made this opportunity available in the cases of young offenders. This review describes the process in the south of Israel. We find this method very powerful, but further studies are needed. Due to resource problems, it will not become mainstream in the near future. PMID- 17334627 TI - Endosonography: new developments in 2006. AB - Recent progress of the data processing applied to ultrasound (US) examination made it possible to develop new software. The US workstation of the last generation thus incorporated a computer into their center that allowed a very precise treatment of the US image. This made it possible to work out new images like three-dimensional (3-D) US, the US of contrast-harmonic associated with the intravenous injection with product with contrast for US, and finally even more recently, elastography. These techniques, currently quite elaborate in percutaneous US, are to be adapted and evaluated with echoendoscopy (EUS). We thus will approach the 3-D EUS successively, then the contribution of the products of contrast for US with the pancreatic EUS, and finally, elastography guided by endosonography. PMID- 17334628 TI - Anesthetic related advances with cyclodextrins. AB - Cyclodextrins encapsulate and electrostatically bind to lipophilic molecules. The exterior of cyclodextrins are water-soluble and maintain aqueous solubility despite encapsulation of non-aqueous soluble molecules. This unique ability to encapsulate lipophilic molecules and maintain water solubility confers numerous pharmacologic advantages for both drug delivery and removal. Cyclodextrins, a component part of supramolecular chemistry, may be in its infancy of anesthetic application but recent advances have been described as novel and revolutionary. A review of current research coupled with an understanding of cyclodextrin properties is necessary to fully appreciate the current uses and future potentials of these unique molecules. PMID- 17334629 TI - Environmental behavior, sources, and effects of chlorinated polycyclic aromatic hydrocarbons. AB - The environmental sources and behaviors of chlorinated 2- to 5-ring polycyclic aromatic hydrocarbons (ClPAHs). ClPAHs are ubiquitous contaminants found in urban air, vehicle exhaust gas, snow, tap water, and sediments. The concentrations of ClPAHs in each of these environments are generally higher than those of dioxins but markedly lower than the concentrations of the parent compounds, PAHs. Environmental data and emission sources analysis for ClPAHs reveal that the dominant process of generation is by reaction of PAHs with chlorine in pyrosynthesis. This secondary reaction process also occurs in aquatic environments. Certain ClPAHs show greater toxicity, such as mutagenicity and aryl hydrocarbon receptor activity, than their corresponding parent PAHs. Investigation of the sources and environmental behavior of ClPAHs is of great importance in the assessment of human health risks. PMID- 17334630 TI - Proteomic profiling of pathological and aged skeletal muscle fibres by peptide mass fingerprinting (Review). AB - In contrast to the traditional biochemical study of single proteins or isolated pathways in health and disease, technical advances in the high-throughput screening of peptides by mass spectrometry have established new ways of identifying entire cellular protein populations in one swift analytical approach. This review discusses the recent progress in the biochemical analysis of skeletal muscle extracts and outlines the mass spectrometry-based proteomics approach for studying muscle tissues in normal and pathobiochemical processes using peptide mass fingerprinting. Individual topics covered include the most commonly inherited muscle disease, X-linked muscular dystrophy, the physiological process of fast-to-slow fibre transformation, and the role of fibre degeneration in age related muscle wasting. Recent proteomic profiling studies of dystrophic muscles have revealed new disease markers in dystrophin-deficient fibres, such as adenylate kinase, the Ca2+-binding protein regucalcin and the small heat shock protein cvHSP. Since these muscle proteins are of low abundance, they have not previously been identified as biomarkers of muscular dystrophy, illustrating the increased sensitivity of modern mass spectrometric techniques. This review outlines comparative proteomic techniques that employ conventional labeling methods, such as Coomassie- or silver-staining. In addition, the most advanced proteomic screening approach currently available, fluorescence difference in-gel electrophoresis, is described and its potential for studying muscle proteomes is critically examined. As an alternative suggestion, the two-dimensional analysis of different protein samples separated in parallel on a single second dimension gel is introduced and the usefulness of this technique for direct comparative investigations is explained. The potential of studying protein complex formation by intraproteomics, estimating the composition of subcellular fraction by subproteomics, and analyzing total muscle protein extracts by mass spectrometry based proteomics, is enormous. Proteomics is one of the most promising new analytical ways of comparing large muscle protein complements and has the potential to decisively improve modern biochemical and biomedical research into neuromuscular disorders. PMID- 17334631 TI - Enhanced mast cell chymase expression in human idiopathic interstitial pneumonia. AB - Previous studies have shown that mast cell chymase induces and promotes fibrogenesis in injured tissues. We studied the roles of mast cell chymase in the fibritic processes of human idiopathic interstitial pneumonias. Frozen tissue sections from human lungs with usual interstitial pneumonia (n=7), nonspecific interstitial pneumonia (n=4) and normal lungs (n=10) were studied immunohistochemically. Monoclonal antibodies against mast cell chymase, tryptase, interleukin-4, and smooth muscle actin were used. Stained cells or areas were quantified by computer-aided morphometry. The numbers of both tryptase-positive mast cells and chymase-positive mast cells were significantly greater in lung tissues with idiopathic interstitial pneumonia than in normal lung tissues. The increase in the number of chymase-positive mast cells in the diseased lung tissues was closely related to an increase in interleukin-4-positive cells, and also to an accumulation of smooth muscle cells and myofibroblasts. Because smooth muscle cell and myofibroblast proliferation is a principal pathological change in idiopathic interstitial pneumonias, these observations suggest that mast cell chymase, possibly induced by interleukin-4-dependent phenotypic modulation, may be an important mediator in the inflammatory and fibrotic processes of idiopathic interstitial pneumonia in humans. PMID- 17334632 TI - Improvement of organ damage by a non-depressor dose of imidapril in diabetic spontaneously hypertensive rats. AB - Many clinical trials have demonstrated that angiotensin converting enzyme inhibitors have protective effects on organ damage, suggesting the importance of inhibition of the renin-angiotensin system. In this study, we investigated the effects of a non-depressor dose of imidapril on organ damage induced by diabetes and hypertension. Diabetes was induced by an intravenous injection of streptozotocin (STZ, 40 mg/kg) in 15-week-old male spontaneously hypertensive rats (SHR). Imidapril (2 mg/kg/day) or vehicle was given orally for 28 days, and then the heart weight, left ventricle mass (LVM), urinary albumin excretion (UAE) and endothelial function were examined, as well as the urinary NOx level and local hepatocyte growth factor (HGF) expression. There were no significant differences between the treated groups in systolic blood pressure and plasma parameters. On the other hand, UAE was significantly suppressed in the imidapril treated group (450+/-44 mg/day) compared to the vehicle-treated group (963+/-182 mg/day) (p<0.01). Moreover, endothelial function assessed by dilative reaction to acetylcholine as well as cardiac hypertrophy assessed by both heart/body weight ratio and LVM were significantly improved in the imidapril-treated group (p<0.05 and p<0.01, respectively). The urinary NOx concentration and local HGF expression in vessel walls were also significantly increased in the imidapril-treated group (p<0.01). A non-depressor dose of imidapril showed protective effects against organ damage in diabetic SHR, which may be partially due to the increase of HGF and NO. PMID- 17334633 TI - Beta amyloid angiogenic activity in vitro and in vivo. AB - Angiogenesis has been suggested as a direct contributor to Alzheimer's disease (AD) pathology. The major pathological hallmarks of AD are the presence of neurofibrillary tangles and, beta-amyloid plaques associated with activated microglia, astrocytes, degenerating neurons and vascular toxicity. In this study, Abeta1-40 and Abeta1-42 peptides, both components of the senile plaques in AD, were used to study their angiogenic activity in vitro, by using normal human cerebral endothelial cells (HCECs), and in vivo, by using the chick embryo chorioallantoic membrane (CAM) assay. Results showed that both peptides stimulate in vitro endothelial cell proliferation, chemotaxis and morphogenesis in Matrigel. Moreover, by using the aorta ring assay, both peptides stimulated the formation of capillary-like structures. An angiogenic response was induced in the CAM assay, similar to that induced by fibroblast growth factor-2 (FGF-2), a well known angiogenic cytokine. Overall, these data support the hypothesis that Abeta peptides may contribute to angiogenesis occurring in AD and suggest that limiting the pro-angiogenic activity of Abeta peptides may therefore provide a useful target to control angiogenesis associated to AD and therefore limit the disease progression. PMID- 17334634 TI - The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin. AB - Skin cancer, the most common cancer in the general population, is strongly associated with exposure to the ultraviolet component of sunlight. To investigate the relationship between DNA damage processing and skin tumour development, we determined the POLH status of a cohort of skin cancer patients. The human POLH gene encodes DNA polymerase eta (poleta), which normally carries out accurate translesion synthesis past the major UV-induced photoproduct, the dithymine cyclobutane dimer. In the absence of active poleta in xeroderma pigmentosum variant (XPV) patients, mutations accumulate at sites of UV-induced DNA damage, providing the initiating step in skin carcinogenesis. Forty patients diagnosed with skin cancer were genotyped for polymorphisms in the POLH protein-coding sequence, using glycosylase-mediated polymorphism detection (GMPD) and direct DNA sequencing of POLH PCR products derived from white blood cell genomic DNA. All individuals carried the wild-type POLH sequence. No POLH mutations were identified in genomic DNA from skin tumours derived from 15 of these patients. As determined by RT-PCR, POLH mRNA was expressed in all normal and skin tumour tissue examined. Poleta protein was also detectable by Western blotting, in two matched normal and skin tumour extracts. An alternatively spliced form of POLH mRNA, lacking exon 2, was more readily detected in skin tissue than in white blood cells from the same patient. Real-time PCR was used to quantify POLH expression in matched normal and skin tumour-derived mRNA from a series of patients diagnosed with either basal or squamous cell carcinoma. Compared to matched normal skin tissue from the same patient, 1 of 7 SCC, and 4 of 10 BCC tumours examined showed at least a 2-fold reduction in POLH expression, while 1 of 7 SCC, and 3 of 10 BCC tumours showed at least a 2-fold increase in POLH expression. Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies between normal and skin tumours in the population under investigation. Knowledge of the POLH status in skin tumours could contribute to an understanding of the role of this gene in the development of the most common cancer in the general population. PMID- 17334635 TI - Oxidative stress-induced poly(ADP-ribosyl)ation in chick limb bud-derived chondrocytes. AB - Oxidative stress has been implicated in the pathogenesis of various diseases affecting chondrogenesis or the function of articular cartilage. DNA damage caused by oxidative stress may trigger the activation of the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) which may contribute to tissue injury. We aimed at investigating the effects of peroxynitrite (100-600 microM) and hydrogen peroxide (0.1-4 mM) on PARP activation and extracellular matrix production of high density micromass cultures (HDC) prepared from chick limb bud mesenchymal cells. We found that both oxidative species strongly inhibited matrix formation of HDCs treated on day 2 but not on day 5. The PARP inhibitor 3-aminobenzamide (3 AB) stimulated matrix production in non-stressed cells and prevented suppressed matrix production in oxidatively stressed cells. Both hydrogen peroxide and peroxynitrite induced PARP activation and poly(ADP-ribose) accumulation. Decreased proliferation, viability and NAD+ content were not or only slightly improved by 3-AB, indicating that 3-AB directly affects matrix formation. In conclusion, oxidative stress stimulates poly(ADP-ribose) metabolism and inhibits extracellular matrix production of HDCs in a PARP-dependent manner. Our findings may have implications for potential therapeutic approaches aimed at restoring the matrix production capacity of chondrogenic cells. PMID- 17334636 TI - Dose-dependent expression changes of early response genes to ionizing radiation in human lymphoblastoid cells. AB - The sensitivity of cancer cells as well as normal cells in response to ionizing radiation (IR) is believed to be associated with the early inducible expression of specific genes. Using cDNA microarray technology, here we explored and compared the global transcriptional changes in human lymphoblastoid AHH-1 cells irradiated with 0.05-, 0.2-, 0.5-, 2.0- and 10-Gy doses of gamma-rays 4 h after exposure. A dose as low as 0.05 Gy was efficient in inducing a transcriptional response including the up-regulation of 25 genes, some of which are involved in signal transduction pathways, e.g. BMPR2, GPR124, MAPK8IP2 and AGGF1, and the down-regulation of 18 genes. Expression of some genes was altered only at a specific dose. Most importantly, we discovered a number of radiation-response genes, e.g. DNA repair gene XPC, tumor protein p53 inducible protein 3 gene (TP53I3), immediate early response 5 gene, whose transcriptional levels were increased or depressed by IR in a dose-dependent trend within the dose range 0.05 10 Gy. The dose-dependent induced expression of TP53I3 and XPC was confirmed by Northern blot analyses. Using quantitative real-time PCR, we further confirmed that XPC gene induction was dose dependent as well as time dependent, reaching a peak 4 h post-2 Gy and 10 h post-0.05 Gy. The maximum induced expression level of the XPC gene was higher after 2 Gy (3.2-fold) than 0.05 Gy (1.93-fold). The identification of these radiation-inducible genes, especially those exhibiting a dose-dependent response, not only expands our knowledge of the mechanisms underlying the diverse biological effects induced by IR, but provides candidates for developing novel biomarkers of radiation injury. PMID- 17334637 TI - Modulation of gene expression in cholesterol-lowering effect of electroacupuncture at Fenglong acupoint (ST40): a cDNA microarray study. AB - The aim of this study was to demonstrate the cholesterol-lowering effect of electroacupuncture (EA) at the acupoint of Fenglong (ST40) in mice and to investigate its molecular mechanism by using genome-wide gene expression profile analysis. Mice with hypercholesterolemia induced by a high-cholesterol diet were randomly divided into EA at ST40 group (EG), EA at non-acupoint group (ENG), and simvastatin group (DG). A lipid profile of both the plasma and liver indicated that EA at ST40 had the same hypocholesterolemic effect as that of simvastatin, while EA at non-acupoint failed to produce the same effect. The global gene expression profile showed that EA at ST40 not only regulated the expression of genes which were directly involved in the cholesterol metabolism in the liver, but also significantly affected the expression of genes involved in signal transduction, transcription regulation, cell cycle, cell adhesion, immunity and stress. The gene expression pattern was further verified by real-time RT-PCR. The mechanism by which EA at ST40 regulated liver cholesterol metabolism is discussed. We conclude that the hypocholesterolemic effect is specific to EA at ST40 and not due to general electrical stimulation of muscles. The comprehensive gene expression profile analysis appears particularly useful in the search for EA induced changes in cholesterol regulation. PMID- 17334638 TI - Gender differences in the association of gene polymorphisms with type 2 diabetes mellitus. AB - Type 2 diabetes mellitus is a complex metabolic disorder in which endogenous sex hormones may contribute to sex-dependent etiologies. We hypothesized that genetic variants related to type 2 diabetes mellitus might differ between men and women. We thus performed a large-scale association study to identify gene polymorphisms associated with type 2 diabetes mellitus in men and women separately. The study population comprised 4854 unrelated Japanese individuals (2688 men, 2166 women), including 1490 subjects with type 2 diabetes mellitus (969 men, 521 women). The genotypes for 16 gene polymorphisms were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis with adjustment for age, body mass index, and smoking status revealed that the T-->G (3' UTR) polymorphism of the thrombospondin 2 gene (THBS2), the -603A-->G polymorphism of the coagulation factor III gene (F3), and the G-->T (intron 2) polymorphism of the adipocyte, C1Q, and collagen domain containing (adiponectin) gene (ADIPOQ) were significantly associated with the prevalence of type 2 diabetes mellitus in men, and that the A-->G (Arg160Gly) polymorphism of the paraoxonase 1 gene (PON1) was significantly associated with this condition in women. A stepwise forward selection procedure demonstrated that genotypes of THBS2, F3, and ADIPOQ were significant determinants of type 2 diabetes mellitus in men, and that genotype of PON1 significantly affected this condition in women. Genotyping of these polymorphisms may prove informative for assessment of the genetic component of type 2 diabetes mellitus for men and women separately. PMID- 17334639 TI - Galanin in the regulation of the hypothalamic-pituitary-adrenal axis (Review). AB - Galanin is a regulatory 30- or 29-amino acid peptide, widely distributed in the nervous system and gut, that acts via three subtypes of G protein-coupled receptors, named GAL-R1, GAL-R2 and GAL-R3. Findings have been accumulated that galanin regulates neuroendocrine hypothalamic axes, including the hypothalamic pituitary-adrenal (HPA) one. Galanin and its receptors are expressed in the hypothalamic paraventricular and supraoptic nuclei, anterior pituitary and adrenal medulla. Adrenal cortex does not express galanin, but is provided with GAL-R1 and GAL-R2. The bulk of evidence indicates that galanin stimulates the activity of the central branch of the HPA axis (i.e. the release of corticotropin releasing hormone and ACTH), thereby enhancing glucocorticoid secretion from the adrenal cortex. Investigations carried out in the rat show that galanin is also able to directly stimulate corticosterone (glucocorticoid) secretion from adrenocortical cells, through GAL-R1 and GAL-R2 coupled to the adenylate cyclase protein kinase A signaling cascade, and nor-epinephrine release from adrenal medulla. There is indication that galanin may also enhance corticosterone release via an indirect paracrine mechanism involving the local release of catecholamines, which in turn activate beta-adrenoceptors located on adrenocortical cells. The physiological relevance in the rat of the glucocorticoid secretagogue action of galanin is suggested by the demonstration that the blockade of galanin system significantly lowers basal corticosterone secretion. There is also evidence that galanin plays a role in the modulation of HPA-axis response to stress, as well as in the pathogenesis of pituitary adenomas and perhaps of pheochromocytomas. PMID- 17334640 TI - Ins2Akita mice exhibit hyperphagia and anxiety behavior via the melanocortin system. AB - Elevated anxiety symptoms have been reported to be present in many patients with diabetes mellitus. The underlying mechanisms by which diabetes mellitus influences behavior remain to be determined. We assessed feeding and anxiety behaviors in spontaneously diabetic Ins2Akita mice. We measured blood glucose, body weight, and food and water intakes in C57BL/6 heterozygote Ins2Akita mice. The behavioral properties of Ins2Akita mice were assessed in an open-field test and an elevated plus-maze. The gene expression of hypothalamic neuropeptides was examined in non-food-deprived Ins2Akita mice. Body weights of the Ins2Akita mice were less than those of the age-matched C57BL/6 mice, as controls. Food and water intakes were increased in the Ins2Akita mice. In the open-field test, the Ins2Akita mice had decreased locomotor activity and increased immobilization time. The Ins2Akita mice exhibited anxiety behavior in the elevated plus-maze. RT PCR analysis showed decreased proopiomelanocortin (POMC) mRNA expression and increased agouti-related protein (AGRP) mRNA expression in Ins2Akita mice. There were no significant differences in hypothalamic ghrelin mRNA expression. These observations indicate that Ins2Akita mice, which are characterized by hypoinsulinemia and hyperglycemia, exhibited hyperphagia and anxiety behavior; the mechanism of action involved the activation of hypothalamic AGRP and the inactivation of hypothalamic POMC. In addition, Ins2Akita mice are a useful model for understanding the mechanisms involved in the psychological complications of diabetes mellitus. Further, melanocortin systems may be therapeutic targets not only for diabetes but also for its associated complications. PMID- 17334641 TI - Suppression of regucalcin mRNA expression in the hearts of rats administered with free radical compound: the administration-induced death is accelerated in regucalcin transgenic rats. AB - The expression of regucalcin, a regulatory protein in the intracellular signaling system, in the hearts of rats was investigated. Regucalcin expression was examined using reverse transcription-polymerase chain reaction and Western blot analysis. Regucalcin mRNA and its protein levels in the hearts of male and female rats were significantly decreased with increasing age (50 weeks old) as compared with that of 5-week-old rats. The effect of 1,1-diphenyl-2-picryl-hydrazyl (DPPH), a compound that produces free radical, on regucalcin mRNA expression in the hearts of female rats (5 weeks old) was examined. Heart regucalcin mRNA levels were significantly decreased at 60 or 180 min after a single intraperitoneal administration of DPPH (0.5 mg /100 g body weight), suggesting that free radical stress has a suppressive effect on the gene expression. Normal (wild) female rats died at approximately 300 min after a single intraperitoneal administration of DPPH (0.5 mg/100 g), while regucalcin transgenic (TG) female rats died at approximately 150 min after the administration. Heart regucalcin protein in DPPH-administered rats was greater in regucalcin TG rats than in normal (wild) rats. This study demonstrates that the death of regucalcin TG rats is accelerated after the administration of free radical compound, indicating that overexpression of regucalcin does not have effects as the suppressor for free radical stress and the scavenger for free radical in rats. PMID- 17334642 TI - Association of total plasma homocysteine with methylenetetrahydrofolate reductase genotypes 677C>T, 1298A>C, and 1793G>A and the corresponding haplotypes in Swedish children and adolescents. AB - We studied 692 Swedish children and adolescents (aged 9-10 or 15-16 years, respectively), in order to evaluate the effect of the methylenetetrahydrofolate reductase (MTHFR) 677C>T, 1298A>C, and 1793G>A polymorphisms on total plasma homocysteine concentrations (tHcy). Genotyping was performed with Pyrosequencing technology. The MTHFR 677C>T polymorphism was associated with increased tHcy concentrations in both the children and the adolescents (P<0.001 for both age groups) in both genders. The effect of MTHFR 1298A>C was studied separately in subjects with the 677CC and 677CT genotypes, and the 1298C allele was found to be associated with higher tHcy levels both when children were stratified according to 677C>T genotypes, and when using haplotype analyses and diplotype reconstructions. The 1793A allele was in complete linkage disequilibrium with the 1298C allele. It was still possible to show that the 1793A allele was associated with lower tHcy levels, statistically significant in the adolescents. In conclusion, a haplotype-based approach was slightly superior in explaining the genetic interaction on tHcy plasma levels in children and adolescents than a simple genotype based approach (R2 adj 0.44 vs. 0.40). The major genetic impact on tHcy concentrations is attributable to the MTHFR 677C>T polymorphism. The common 1298A>C polymorphism had a minor elevating effect on tHcy, whereas the 1793G>A polymorphism had a lowering effect on tHcy. PMID- 17334643 TI - Quantitative analysis of the impact of short-time high hydrostatic pressure on bone tumor-associated proteases. AB - In orthopedic surgery, sterilization of bone used for reconstruction of osteoarticular defects caused by malignant tumors is carried out in various ways. At present, to devitalize tumor-bearing osteochondral segments, extracorporeal irradiation or autoclaving is mainly used, although both methods have substantial disadvantages, leading to a significant loss of biomechanical and biological integrity of the bone. As an alternative approach, a new technology to achieve bone sterilization, the high hydrostatic pressure (HHP) treatment of bone, has been suggested, which is currently being preclinically tested. This novel technique leads to the inactivation of tumor cells without impairing biomechanical properties of the bone, cartilage, or tendons. HHP may not only exert an effect on tumor and normal cells present in the bone but also on tumor associated proteases released by these cells, which are conductive to tumor bone turnover. In order to investigate this, proteolytic key enzymes, e.g. MMP-9, uPA, t-PA, plasmin, trypsin, and thrombin were subjected to HHP T (Arg54Trp) polymorphism of QPCT, the C-->T (Pro198Leu) polymorphism of GPX1, the 137,346T- >C polymorphism of FYN, the -344C-->T polymorphism of CYP11B2, and the A-->G (Ser49Gly) polymorphism of ADRB1 were determined with a fluorescence-based allele specific DNA primer assay system; those for the A-->G polymorphism of CNR2, the I/D (22,375delAC) polymorphism of CAV1, and the -1213T-->C polymorphism of ESR2 by melting curve analysis, and that for the (GT)n polymorphism of COL1A2 were determined by DNA fragment analysis. The polymorphism of FYN was associated with systolic and diastolic BP in women. In men, polymorphisms of CNR2, QPCT, GPX1, COL1A2, CYP11B2, and ESR2 were associated with systolic and diastolic BP, those of CAV1 and FYN with systolic BP, and that of ADRB1 with diastolic BP. The polymorphisms of QPCT and CYP11B2 were also associated with the prevalence of hypertension in men. These results suggest that polymorphisms of QPCT and CYP11B2 are determinants of BP and the development of hypertension in Japanese men. PMID- 17334645 TI - Antiviral effect of octyl gallate against influenza and other RNA viruses. AB - Octyl gallate inhibited the multiplication of several RNA viruses with widely different structure and replication strategies; i.e. vesicular stomatitis virus (VSV), influenza virus and poliovirus. In addition, octyl gallate showed virucidal activity against enveloped viruses at high concentrations. Characterization of the mode of action of octyl gallate against influenza virus infection revealed that the reagent delayed the onset of progeny virus formation. It did not, however, affect the rate of the formation, and the addition of the reagent at 2 h postinfection (p.i.), but not at 4 h p.i., almost completely abolished the formation of the progeny viruses, suggesting that the antiviral action of octyl gallate was not the result of a non-specific degeneration of the infected cells, but possibly the result of the inhibition at specific steps in the middle stage of the multiplication of influenza virus. PMID- 17334646 TI - Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-kappaB signaling in human gastric carcinoma cells. AB - The gastric pathogen, helicobacter pylori (H. pylori), has been associated with the progression of gastric cancer. It was previously reported that H. pylori induced urokinase plasminogen activator receptor (uPAR) expression and stimulated cell invasiveness in human gastric cancer AGS cells. However, the precise mechanisms for how H. pylori upregulates uPAR are unclear. This study investigated the underlying signal pathways in H. pylori-induced uPAR in human gastric cancer AGS cells. The intracellular H2O2 content, as determined using H2O2-sensitive probe 2',7'-dichlorodihydrofluorescein, increased after the H. pylori treatment. N-acetyl cysteine (NAC), an antioxidant, prevented the H. pylori-induced production of H2O2 and uPAR expression. In addition, exogenous H2O2 was found to increase uPAR mRNA expression and its promoter activity. Site directed mutagenesis of the potential NF-kappaB element in the uPAR promoter showed that the redox-sensitive transcription factor NF-kappaB was essential for H. pylori-induced uPAR expression. The expression of vectors encoding a mutated type NF-kappaB-inducing kinase and I-kappaB, and a specific inhibitor of NF kappaB (BAY11-7082) decreased the H. pylori-induced uPAR promoter activity. Chromatin immunoprecipitation and the electrophoretic mobility shift assay confirmed that H. pylori increased the DNA binding activity of NF-kappaB. With the aid of NAC and H2O2, it was determined that reactive oxygen species (ROS) is an upstream signaling molecule for activating the NF-kappaB induced by H. pylori. The enhanced AGS cell invasiveness by H. pylori was partially abrogated by an NAC and BAY11-7082 treatment. These results suggest that the ROS and NF-kappaB signaling pathway is important in H. pylori-induced uPAR expression and the increased cell invasiveness of human gastric cancer AGS cells. PMID- 17334647 TI - AP1- and NF-kappaB-binding sites conserved among mammalian WNT10B orthologs elucidate the TNFalpha-WNT10B signaling loop implicated in carcinogenesis and adipogenesis. AB - WNT signals are context-dependently transduced to canonical and non-canonical signaling cascades. We cloned and characterized wild-type human WNT10B, while another group cloned aberrant human WNT10B with Gly60Asp amino-acid substitution. Proto-oncogene WNT10B is expressed in gastric cancer, pancreatic cancer, breast cancer, esophageal cancer, and cervical cancer. Because WNT10B blocks adipocyte differentiation, coding SNP of WNT10B gene is associated with familial obesity. In 2001, we reported WNT10B upregulation by TNFalpha. Here, comparative integromics analyses on WNT10B orthologs were performed to elucidate the transcriptional mechanism of WNT10B. Chimpanzee WNT10B and cow Wnt10b genes were identified within NW_001223159.1 and AC150975.2 genome sequences, respectively, by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee WNT10B and cow Wnt10b showed 98.7% and 95.1% total-amino-acid identity with human WNT10B, respectively. N-terminal signal peptide, 24 Cys residues, two Asn-linked glycosylation sites, and Gly60 of human WNT10B were conserved among mammalian WNT10B orthologs. Transcription start site of human WNT10B gene was 106-bp upstream of NM_003394.2 RefSeq 5'-end. Number of GC di-nucleotide repeats just down-stream of WNT10B transcription start site varied among primates and human population. Comparative genomics analyses revealed that double AP1-binding sites in the 5'-flanking promoter region and NF-kappaB-binding site in intron 3 were conserved among human, chimpanzee, cow, mouse, and rat WNT10B orthologs. Because TNFalpha signaling through TNFR1 and TRADD/RIP/TRAF2 complex activates JUN kinase (JNK) and IkappaB kinase (IKK) signaling cascades, conserved AP1- and NF-kappaB binding sites explain the mechanism of TNFalpha-induced WNT10B upregulation. TNFalpha-WNT10B signaling loop is the negative feedback mechanism of adipogenesis to prevent obesity and metabolic syndrome. On the other hand, TNFalpha-WNT10B signaling loop is implicated in carcinogenesis. Inhibitors of TNFalpha-WNT10B signaling loop could be utilized for the prevention or treatment of cancer associated with chronic inflammation, such as gastric, liver, breast and pancreatic cancer. PMID- 17334648 TI - Effective inhibition of hepatitis B virus replication by small interfering RNAs expressed from human foamy virus vectors. AB - RNA interference (RNAi) mediated by double- stranded small interfering RNA (siRNA) is a novel mechanism of sequence-specific, post-transcriptional gene silencing. There has been much research into the use of RNAi for the treatment of human diseases. Many viruses, including hepatitis B virus (HBV), are susceptible to inhibition by this mechanism. However, for RNAi to be efficacious therapeutically, effective RNAi targeting sequences and a suitable delivery system are required. In this study, we employed a polymerase chain reaction (PCR) based siRNA expression strategy to rapidly screen for effective siRNA sequences. Two effective siRNAs sequences (designated as S2 and X1) which reduced the HBV RNA by >90% were identified. For delivering the siRNAs, they were cloned into a human foamy virus (HFV)-based vector to generate single siRNA expression vectors HFVU6-siS2, HFVU6-siX1 and a dual siRNA expression vector HFVU6-siSX. The results showed that these siRNA vectors effectively inhibited multiple HBV gene expression and viral DNA replication based on ELISA and quantitative PCR analysis. HFVU6-siSX which simultaneously expressed two siRNAs that targeted the S and X genes of HBV is the most potent inhibitor of HBV replication. In addition, the repression of HBV RNA and DNA was stable for up to 3 months post transduction as determined by RT-PCR and Southern blotting. Collectively, the PCR based siRNA expression strategy provides a rapid and easy approach for testing candidate anti-HBV siRNA sequences and for cloning selected siRNA expression cassettes into a vector. RNAi based on the HFV vector was able to achieve effective, long-term inhibition of HBV gene expression and viral DNA replication. The combination of the two techniques may provide a powerful tool in the treatment of viral infection. PMID- 17334649 TI - Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes. AB - AIMS/HYPOTHESIS: There is evidence that type 2 diabetes mellitus is associated with cognitive impairment. Most studies investigating this association have evaluated elderly individuals, after many years of diabetes, who generally have poor glycaemic control and significant vascular disease. The aim of the current study was to investigate the early cognitive consequences and associated brain correlates of type 2 diabetes. MATERIALS AND METHODS: With regard to cognition and brain measures, we compared 23 age-, sex- and education-matched control subjects with 23 mostly middle-aged individuals with relatively well-controlled diabetes of less than 10 years from the time of diagnosis. RESULTS: We found deficits in hippocampal-based memory performance and preservation of other cognitive domains. Relative to control subjects, individuals with diabetes had reductions in brain volumes that were restricted to the hippocampus. There was an inverse relationship between glycaemic control and hippocampal volume; in multivariate regression analysis, HbA(1c) was the only significant predictor of hippocampal volume, accounting for 33% of the observed variance. Other variables commonly associated with type 2 diabetes, such as elevated BMI, hypertension or dyslipidaemia, did not independently contribute to the variance in hippocampal volume. CONCLUSIONS/INTERPRETATION: These results suggest that the medial temporal lobe may be the first brain site affected by type 2 diabetes and that individuals in poorer metabolic control may be affected to a greater extent. PMID- 17334650 TI - A type 1 diabetes subgroup with a female bias is characterised by failure in tolerance to thyroid peroxidase at an early age and a strong association with the cytotoxic T-lymphocyte-associated antigen-4 gene. AB - AIMS/HYPOTHESIS: HLA haplotypes DRB1*03_DQB1*02 and DRB1*04_DQB1*0302, and allelic variation of the T cell regulatory gene cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) and of the T cell activation gene protein tyrosine phosphatase, non-receptor type 22 (lymphoid) (PTPN22) have been associated with type 1 diabetes and autoimmune thyroid disease. Using thyroid peroxidase autoantibodies (TPOAbs) as an indicator of thyroid autoimmunity, we assessed whether the association of these loci is different in type 1 diabetes patients with TPOAbs than in those without. MATERIALS AND METHODS: TPOAbs were measured in 4,364 type 1 diabetic patients from across Great Britain, 67% of whom were aged under 18 years. These patients and 6,866 geographically matched control subjects were genotyped at CTLA4, PTPN22, HLA-DRB1 and HLA-DQB1. RESULTS: TPOAbs were detected in 462 (10.6%) of the type 1 diabetic patients. These patients had a stronger association with CTLA4 (odds ratio [OR] = 1.49 for the G allele of the single nucleotide polymorphism rs3087243; 95% CI = 1.29-1.72) than did the TPOAbs negative patients (p = 0.0004; OR = 1.16; 95% CI = 1.10-1.24) or type 1 diabetes patients overall (OR = 1.20; 95% CI = 1.13-1.27). The ratio of women:men was higher (1.94:1) in this subgroup than in type 1 diabetes patients without TPOAbs (0.94:1; p = 1.86 x 10(-15)). TPOAbs status did not correlate with age at diagnosis of type 1 diabetes or with PTPN22 (Arg620Trp; rs2476601). CONCLUSIONS/INTERPRETATION: Our results identify a subgroup of type 1 diabetic patients that is sensitive to allelic variation of the negative regulatory molecule CTLA-4 and indicate that TPOAbs testing could be used to subclassify type 1 diabetes patients for inclusion in genetic, biological or clinical studies. PMID- 17334651 TI - Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. AB - AIMS/HYPOTHESIS: Insulin resistance and type 2 diabetes are associated with mitochondrial dysfunction. The aim of the present study was to test the hypothesis that oxidative phosphorylation and electron transport capacity are diminished in the skeletal muscle of type 2 diabetic subjects, as a result of a reduction in the mitochondrial content. MATERIALS AND METHODS: The O(2) flux capacity of permeabilised muscle fibres from biopsies of the quadriceps in healthy subjects (n = 8; age 58 +/- 2 years [mean+/-SEM]; BMI 28 +/- 1 kg/m(2); fasting plasma glucose 5.4 +/- 0.2 mmol/l) and patients with type 2 diabetes (n = 11; age 62 +/- 2 years; BMI 32 +/- 2 kg/m(2); fasting plasma glucose 9.0 +/- 0.8 mmol/l) was measured by high-resolution respirometry. RESULTS: O(2) flux expressed per mg of muscle (fresh weight) during ADP-stimulated state 3 respiration was lower (p < 0.05) in patients with type 2 diabetes in the presence of complex I substrate (glutamate) (31 +/- 2 vs 43 +/- 3 pmol O(2) s(-1) mg(-1)) and in response to glutamate + succinate (parallel electron input from complexes I and II) (63 +/- 3 vs 85 +/- 6 pmol s(-1) mg(-1)). Further increases in O(2) flux capacity were observed in response to uncoupling by FCCP, but were again lower (p < 0.05) in type 2 diabetic patients than in healthy control subjects (86 +/- 4 vs 109 +/- 8 pmol s(-1) mg(-1)). However, when O(2) flux was normalised for mitochondrial DNA content or citrate synthase activity, there were no differences in oxidative phosphorylation or electron transport capacity between patients with type 2 diabetes and healthy control subjects. CONCLUSIONS/INTERPRETATION: Mitochondrial function is normal in type 2 diabetes. Blunting of coupled and uncoupled respiration in type 2 diabetic patients can be attributed to lower mitochondrial content. PMID- 17334652 TI - Suppression of glucagon secretion is lower after oral glucose administration than during intravenous glucose administration in human subjects. AB - AIMS/HYPOTHESIS: The incretin effect describes the augmentation of postprandial insulin secretion by gut hormones. It is not known whether glucagon secretion is also influenced by an incretin effect. A glucagon suppression deficiency has been reported in some patients with type 2 diabetes, but it is unclear whether this abnormality is present prior to diabetes onset. We therefore addressed the questions: (1) Is glucagon secretion different after oral and during intravenous glucose administration? (2) If so, is this related to the secretion of incretin hormones? (3) Is glucagon secretion abnormal in first-degree relatives of patients with type 2 diabetes? MATERIALS AND METHODS: We examined 16 first-degree relatives of patients with type 2 diabetes and ten matched control subjects with an oral glucose load (75 g) and with an 'isoglycaemic' intravenous glucose infusion. RESULTS: Glucagon levels were significantly suppressed by both oral and intravenous glucose (p < 0.0001), but glucagon suppression was more pronounced during intravenous glucose administration (76 +/- 2%) than after oral glucose administration (48 +/- 4%; p < 0.001). The differences in the glucagon responses to oral and i.v. glucose were correlated with the increments in gastric inhibitory polypeptide (GIP) (r = 0.60, p = 0.001) and glucagon-like peptide (GLP)-1 (r = 0.46, p < 0.05). There were no differences in glucagon levels between first-degree relatives and control subjects. CONCLUSIONS/INTERPRETATION: Despite the glucagonostatic actions of GLP-1, the suppression of glucagon secretion by glucose is diminished after oral glucose ingestion, possibly due to the glucagonotropic actions of GIP and GLP-2. Furthermore, in this group of first degree relatives, abnormalities in glucagon secretion did not precede the development of other defects, such as impaired insulin secretion. PMID- 17334653 TI - Improved glucose tolerance in mice receiving intraperitoneal transplantation of normal fat tissue. AB - AIMS/HYPOTHESIS: The association between increased (visceral) fat mass, insulin resistance and type 2 diabetes mellitus is well known. Yet, it is unclear whether the mere increase in intra-abdominal fat mass, or rather functional alterations in fat tissue in obesity contribute to the development of insulin resistance in obese patients. Here we attempted to isolate the metabolic effect of increased fat mass by fat tissue transplantation. METHODS: Epididymal fat pads were removed from male C57Bl6/J mice and transplanted intraperitoneally into male littermates (recipients), increasing the combined perigonadal fat mass by 50% (p < 0.005). At 4 and 8 weeks post-transplantation, glucose and insulin tolerance tests were performed, and insulin, NEFA and adipokines measured. RESULTS: Circulating levels of NEFA, adiponectin and leptin were not significantly different between transplanted and sham-operated control mice, while results of the postprandial insulin tolerance test were similar between the two groups. In contrast, under fasting conditions, the mere increase in intra-abdominal fat mass resulted in decreased plasma glucose levels (6.9 +/- 0.4 vs 8.1 +/- 0.3 mmol/l, p = 0.03) and a approximately 20% lower AUC in the glucose tolerance test (p = 0.02) in transplanted mice. Homeostasis model assessment of insulin resistance (HOMA-IR) was 4.1 +/- 0.4 in transplanted mice (vs 6.2 +/- 0.7 in sham-operated controls) (p = 0.02), suggesting improved insulin sensitivity. Linear regression modelling revealed that while total body weight positively correlated, as expected, with HOMA-IR (beta: 0.728, p = 0.006), higher transplanted fat mass correlated with lower HOMA-IR (beta: -0.505, p = 0.031). CONCLUSIONS/INTERPRETATION: Increasing intra-abdominal fat mass by transplantation of fat from normal mice improved, rather than impaired, fasting glucose tolerance and insulin sensitivity, achieving an effect opposite to the expected metabolic consequence of increased visceral fat in obesity. PMID- 17334654 TI - Phenotype-specific inhibition of the vascular smooth muscle cell cycle by high glucose treatment. AB - AIMS/HYPOTHESIS: Diabetes accelerates the development of atherosclerosis, which critically involves the proliferation of vascular smooth muscle cells (SMCs). However, how high glucose treatment regulates SMC proliferation is controversial. Considering the established SMC heterogeneity, we hypothesised that glucose treatment may have distinct effects on proliferation of the various phenotypic SMCs. MATERIALS AND METHODS: We tested this possibility using cloned spindle shaped and epithelioid SMCs and laser scanning cytometry. RESULTS: Our results showed that glucose treatment significantly inhibited the serum-independent proliferation of epithelioid SMCs, but had no effect on the proliferation of spindle-shaped cells either with or without serum stimulation. Furthermore, glucose treatment inhibited DNA synthesis, as detected by bromodeoxyuridine (BrdU) incorporation, and increased the production of reactive oxygen species in epithelioid SMCs. The inhibition of BrdU incorporation by glucose treatment was mimicked by glucosamine and phorbol 2,13-dibutyrate, a protein kinase C (PKC) activator, and reversed by azaserine, an inhibitor of the hexosamine pathway. In addition, the inhibitory effects of glucose treatment were blocked by GF 109203X (a PKC inhibitor) and PD98058 (a MAPK/ERK kinase, MEK inhibitor), and by knockdown of MEK1 by small interfering RNA (siRNA). The addition of either GF 109203X or PD98058 also reduced the phosphorylation of MAP kinase induced by glucose treatment. CONCLUSIONS/INTERPRETATION: Glucose treatment inhibits the proliferation of epithelioid, but not spindle-shaped, vascular SMCs through the activation of PKC and the MAP kinase pathway, suggesting that the effects of hyperglycaemia on vascular disease depend on the phenotype of SMCs involved. PMID- 17334655 TI - Faithful tissue-specific expression of the human chromosome 21-linked COL6A1 gene in BAC-transgenic mice. AB - We created transgenic mice with a bacterial artificial chromosome (BAC) containing the human COL6A1 gene. In high-copy and low-copy transgenic lines, we found correct temporal and spatial expression of COL6A1 mRNA, paralleling the expression of the murine Col6a1 gene in a panel of nine adult and four fetal organs. The only exception was the fetal lung, in which the transgene was expressed poorly compared with the endogenous gene. Expression of COL6A1 mRNA from the transgene was copy number-dependent, and the increased gene dosage correlated with increased production of collagen VI alpha 1 in skin and heart, as indicated by Western blotting and immunohistochemistry. COL6A1 maps to Chromosome 21 and this gene has been a candidate for contributing to cardiac defects and skin abnormalities in Down syndrome. The low-copy and high-copy COL6A1 transgenics were born and survived in normal Mendelian proportions, without cardiac malformations or altered skin histology. These data indicate that the major promoter and enhancer sequences regulating COL6A1 expression are present in this 167-kb BAC clone. The lack of a strong cardiac or skin phenotype in the COL6A1 BAC-transgenic mice suggests that the increased expression of this gene does not, by itself, account for these phenotypes in Down syndrome. PMID- 17334656 TI - Identification of differentially expressed genes in senescence-accelerated mouse testes by suppression subtractive hybridization analysis. AB - Senescence-accelerated mouse (SAM) strains constitute a model of accelerated senescence coupled with a short lifespan and the early development of various age related disorders. To identify differential gene expression in testes between senescence-accelerated SAMP1 and control SAMR1 mice, we performed suppression subtractive hybridization. We observed that the expression of three genes related to cell proliferation (myosin regulatory light chain B, aldolase 1A isoform, and cytochrome c oxidase subunit VIc) were upregulated and four genes implicated in spermatogenesis were downregulated in SAMP1 mice. Asb-8, a member of ankyrin repeat-containing proteins, was abundantly expressed in the testes and downregulated in SAMP1. The other three downregulated genes (germ cell-specific gene 1, T-complex polypeptide 1b, and activator of cAMP responsive element modulator in testis) have been reported to regulate late-stage spermatogenesis. These gene expression profiles might explain the findings of early testicular maturation and rapid decline in the ability to produce spermatozoa with advancing age in SAMP1 mice. PMID- 17334657 TI - Loss of Chd7 function in gene-trapped reporter mice is embryonic lethal and associated with severe defects in multiple developing tissues. AB - CHD7 is a novel chromodomain gene mutated in 60%-80% of humans with CHARGE syndrome, a multiple congenital anomaly condition characterized by ocular coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and characteristic ear abnormalities including deafness. Phenotypic features of CHARGE are highly variable and incompletely penetrant. To explore developmental roles of CHD7, we generated mice carrying the Chd7(Gt) allele from a Chd7-deficient, gene-trapped lacZ reporter ES cell line. RT-PCR of embryo RNA demonstrated significantly reduced levels of wild-type transcript in Chd7(Gt/Gt) embryos. Chd7(Gt/Gt) embryos survive only up to embryonic day 10.5 (E10.5). Chd7(Gt/+) male and female mice are viable, small, and exhibit variable degrees of head-bobbing and circling, consistent with vestibular dysfunction. Paint-filling of E16.5 heterozygous inner ears revealed defects of the semicircular canals. The pattern of beta-galactosidase activity in Chd7(Gt/+) embryos mimics Chd7 mRNA expression in wild-type embryos, confirming the fidelity of the lacZ reporter. We observed tissue-specific beta-galactosidase in the E12.5 and E14.5 Chd7(Gt/+) brain, pituitary, ear, heart, and craniofacial structures, indicating survival of Chd7(Gt/+) cells in CHARGE-relevant organs. These studies demonstrate the utility of Chd7(Gt) as a reporter-tagged loss-of-function allele for future studies exploring developmental mechanisms of Chd7 deficiency. PMID- 17334658 TI - The Nramp1AA genotype confers susceptibility to Brucella abortus in water buffalo. AB - The 3' untranslated region of the water buffalo Nramp1 (natural resistance associated macrophage protein 1) gene contains two alleles (Nramp1A and Nramp1B), as detected by the denaturing gradient gel electrophoresis (DGGE) technique. The Nramp1BB genotype is associated with resistance of water buffalo to the intracellular pathogen Brucella abortus. This article provides evidence that the Nramp1AA genotype is associated with susceptibility to the same pathogen. Susceptibility or resistance of water buffalo to B. abortus was established by agglutination, complement fixation, and skin tests. The Nramp1 genotype was established by DGGE analysis. The association between the Nramp1AA genotype and susceptibility to B. abortus was demonstrated in two independent population samples (152 cases and 281 controls; 87 cases and 124 controls, respectively). Macrophages from Nramp1AA subjects displayed a lower Nramp1 mRNA level when compared with macrophages from Nramp1BB subjects. Also, monocytes and macrophages from Nramp1AA subjects displayed a higher number of viable intracellular bacteria in comparison with monocytes and macrophages from Nramp1BB animals, providing biological significance to the results from association studies. PMID- 17334659 TI - Two Norwegian sisters with late onset Creutzfeldt-Jakob disease caused by the E200K mutation. PMID- 17334660 TI - Interplay of cerebral autoregulation and neurovascular coupling evaluated by functional TCD in different orthostatic conditions. AB - BACKGROUND: Adequate cerebral blood flow (CBF) is mainly governed by neurovascular coupling (NC) which adapts local CBF to underlying cortical activity,and cerebral autoregulation (CA)that tends to maintain constant CBF despite changes in arterial blood pressure (BP). Since it was suggested that resistance vessels play an important role in both mechanisms, we investigated the irregulative interplay by performing a functional transcranial Doppler(f-TCD) test under different orthostatic conditions. METHODS: Fifteen healthy volunteers performed a visual reading test stimulation task after stabilized in sitting, supine and upright position on a tilt table. Simultaneously, BP and heart rate (HR) were recorded by a photoplethysmographic method and CBF velocity was measured with TCD in left posterior cerebral artery, and, as a reference, also in right middle cerebral artery. Evoked flow velocity (FV) responses were evaluated by a control system approach for systolic and diastolic data. Parameters studied were baseline FV with eyes closed, stable FV under stimulation (gain), oscillatory feature (natural frequency) and damping (attenuation) of the control system model, rate time, and also systolic and diastolic BP and HR. ANOVA test was used for comparing the values of variables in different postural settings, inferring statistical significance at a p < 0,05 level. RESULTS: Although there was a significant variation on the different orthostatic conditions in systolic (p = 0,027) and diastolic (p = 0,001) BP and HR (p = 0,0001), there was no significant change in the basal or evoked CBF velocities. CONCLUSIONS: An intact CA compensates the different orthostatic conditions completely thus allowing an independent regulation of NC according to the metabolic needs of cortical stimulation. PMID- 17334661 TI - Progression of brain atrophy in multiple system atrophy. A longitudinal VBM study. AB - In this study, we aimed to determine the progression of brain atrophy in the parkinson variant of multiple system atrophy (MSA-P). Voxel-based morphometry was applied to two consecutive high resolution MR images of 14 patients with probable MSA-P in comparison to 14 patients with Parkinson's disease (PD). The time interval between baseline and follow-up investigations (1.0 +/- 0.5 SD years in MSAP and 1.4 +/- 0.6 SD years in PD patients) was introduced as covariate in the statistical analysis. Additionally, correlation analyses were performed between the progression maps and clinical data. We observed marked progression of brain atrophy in the MSA-P cohort, the regions including striatum, mesencephalon, thalamus and cerebellum, but also cortical regions such as the primary sensorimotor cortex, supplementary motor area, lateral premotor cortex, medial frontal gyrus, middle frontal gyrus, orbito-frontal cortex,insula, posterior parietal cortex and hippocampus. Short disease duration was correlated with progression of atrophy in the striatum whereas longer disease duration was correlated with increasing atrophy in the cortical areas and cerebellar hemispheres. The UPDRS-III score was not significantly correlated with any brain region. Our data suggest that cortical atrophy is prominent in MSA-P and early degeneration of the basal ganglia drives late onset cortical atrophy. PMID- 17334663 TI - Melatonin biosynthesis in the thymus of humans and rats. AB - Melatonin is an indoleamine widely distributed in the evolution that shows a great functional versatility, playing an important role as a transmitter of photoperiodic information and exhibiting antioxidant, oncostatic, anti-aging and immunomodulatory properties. In vertebrates, this molecule is produced by the pineal gland and other extrapineal sites. The present study was carried out to investigate the presence of melatonin in thymus and the possibility of an endogenous melatonin synthesis in this organ, in which T cells are matured. In this work, we demonstrate in humans and rats that thymus contains melatonin, expresses the mRNAs encoding N-acetyltransferase and hydroxyindol-O methyltransferase, the two key enzymes of the melatonin synthesis, and has this biosynthetic machinery activated. In addition, rat thymocytes cultured for 24 h exhibited high levels of melatonin. The results presented here suggest that human and rat thymuses are able to synthesize melatonin, which could have intracrine, autocrine and paracrine functions. PMID- 17334664 TI - Toll-like receptor signalling and the clinical benefits that lie within. AB - TLRs are of crucial importance to the innate immune system by recognising molecules that are broadly shared by pathogens but distinguishable from host molecules. The innate immune system works to defend the body from microbial infection by initiating inflammation, the extreme form of which is sepsis. The discovery that endogenous ligands, as well as microbial components, are recognised by TLRs, raise the possibility of these receptors and their associated adapter molecules, as potential targets for the development of agonists and antagonists for the treatment of various pathological diseases, and their manipulation as potential adjuvants in vaccine development. By elucidating the mechanisms of TLR signalling pathways involving adapter molecules like MyD88, Mal, TRIF and TRAM combined with the identification of single nucleotide polymorphisms (SNPs) within these receptors and the unique genes that are expressed upon recognition, will assist in the development of therapeutics to alleviate the consequences of microbial-mediated inflammation, which include inflammatory disorders and septic shock. PMID- 17334662 TI - Antimyelin antibodies in clinically isolated syndromes correlate with inflammation in MRI and CSF. AB - OBJECTIVE: We investigated the correlation of antimyelin oligodendrocyte glycoprotein-(anti-MOG) and anti-myelin basic protein antibodies (anti-MBP) in serum of CIS patients with inflammatory signs in MRI and in CSF and, as previously suggested,the incidence of more frequent and rapid progression to clinically definite MS (CDMS). METHODS: 133CIS patients were analysed for anti MOG and anti-MBP (Western blot). Routine CSF and cranial MRI (quantitatively and qualitatively) measures were analyzed. 55 patients had a follow-up of at least 12 months or until conversion to CDMS. RESULTS: Patients with anti-MOG and anti-MBP had an increased intrathecal IgG production and CSF white blood cell count(p = 0.048 and p = 0.036). When anti-MBP alone, or both antibodies were present the cranial MRI showed significantly more T2 lesions (p = 0.007 and p = 0.01,respectively). There was a trend for more lesion dissemination in anti-MBP positive patients (p = 0.076).Conversely, anti-MOG- and/or anti-MBP failed to predict conversion to CDMS in our follow-up group (n = 55). Only in female patients with at least one MRI lesion (n = 34) did the presence of anti-MOG correlate with more frequent (p = 0.028) and more rapid (p = 0.0209) transition to CDMS. CONCLUSIONS: Presence of anti-MOG or anti-MBP or both was not significantly associated with conversion to CDMS in our CIS cohort. However, patients with anti-MOG and anti-MBP had higher lesion load and more disseminated lesions in cranial MRI as well as higher values for CSF leucocytes and intrathecal IgG production. Our data support a correlation of anti-MOG and anti MBP to inflammatory signs in MRI and CSF. The prognostic value of these antibodies for CDMS, however, seems to be less pronounced than previously reported. PMID- 17334665 TI - Comparison of interferon-gamma response between tuberculosis and non-tubercular pneumonia. AB - OBJECTIVE AND DESIGN: Macrophages aided by interferon-gamma (IFN-gamma) are vital to controlling Mycobacterium tuberculosis (M. tuberculosis) infection. Although numerous studies have compared IFN-gamma response between tubercular patients and healthy controls, no studies have investigated IFN-gamma response in patients with pulmonary tuberculosis and non-tubercular pneumonia. The aim of this work was to examine the difference in IFN-gamma response between patients with tuberculosis and non-tubercular pneumonia. METHODS: IFN-gamma production was detected based on the difference in supernatants between non-stimulated and stimulated peripheral blood mononuclear cells by phytohemagglutinin in 83 tubercular patients and 47 patients with pneumonia. Presence of a cavity on chest radiography and co-morbidities of pneumoconiosis, bronchiectasis, liver cirrhosis, renal failure on hemodialysis, diabetes mellitus (DM) and lung cancer were recorded for analysis. RESULTS: Interferon-gamma response, DM and a cavity on chest radiography were independent factors for predicting active pulmonary tuberculosis. Interferon-gamma response was decreased in patients with pulmonary tuberculosis compared with that in patients with non-tubercular pneumonia. Notably, M. tuberculosis infection was the principal factor correlated with IFN gamma response. CONCLUSION: The IFN-gamma response was principally affected by M. tuberculosis infection and not by other co-morbidities. Further study is required to identify the mechanism of decreased IFN-gamma production. PMID- 17334666 TI - Effect of iguratimod and other anti-rheumatic drugs on adenocarcinoma colon 26 induced cachexia in mice. AB - OBJECTIVE: To examine the effect of iguratimod (T-614) and other anti-rheumatic drugs on a mouse model of adenocarcinoma-induced cachexia. METHODS: Cachexia was induced in BALB/c mice by s.c. inoculation of colon 26/clone 20 cells (day 0). The drugs were administered p.o. daily from day 0 for 15 days for prophylactic experiments and from day 7 for 8 days for therapeutic experiments. Serum biochemical parameters and wasting of adipose tissue and muscle were evaluated as the nutritional condition in tumor-bearing mice at day 14. Interleukin-6 (IL-6) levels in serum and tumor tissue of those mice were also quantified. RESULTS: Administration of T-614 did not inhibit the tumor growth, but it resulted in attenuation of cachexia symptoms, such as the reduction in epididymal fat and gastrocnemius muscle, and the decrease of serum albumin. Furthermore, T-614 decreased the serum levels of IL-6, and reduced its gene expression in the tumor tissues. Exogenously administered IL-6 nullified the suppressive effect of T-614. Prednisolone prevented the weight loss and the wasting without inhibiting tumor growth. Methotrexate and indomethacin did not exert any preferable effects in a therapeutic dosing schedule. CONCLUSIONS: Our results demonstrate that T-614 exerts an anticachectic effect in tumor-bearing mice through the inhibition of IL 6 gene expression. PMID- 17334667 TI - Blockade of macrophage migration inhibitory factor (MIF) prevents the antigen induced response in a murine model of allergic airway inflammation. AB - OBJECTIVE AND DESIGN: The role of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, was tested using a mouse asthma model. MATERIALS: One hundred and four male BALB/c mice were used in this study. TREATMENT: Mice were actively sensitized with an intraperitoneal injection of ovalbumin (OVA) and challenged with repeated nebulization of 1 w/v% OVA. Polyclonal anti-MIF antibody was intraperitoneally injected at 10 mg/kg during the antigen challenge period. METHODS: Bronchoalveolar lavage (BAL) was performed 8 h after the last challenge. Airway hyperresponsiveness to inhaled methacholine was measured 24 h after the last challenge. RESULTS: Antigen challenge to immunized mice induced increase in inflammatory cells and concentration of Th2 cytokines in BAL fluid (BALF), and caused the development of airway hyperresponsiveness. Anti-MIF antibody significantly decreased the numbers of inflammatory cells including macrophages, eosinophils, lymphocytes and neutrophils in BALF from OVA-challenged mice. Prednisolone decreased the numbers of eosinophils, lymphocytes and neutrophils but not macrophages. Anti-MIF antibody reduced airway hyperresponsiveness. Anti MIF antibody affected neither the cytokine levels in BALF nor the IgE levels in serum. CONCLUSION: MIF was involved in the antigen-induced inflammatory cell accumulation in the lung and airway hyperresponsiveness without affecting immune responses. PMID- 17334668 TI - Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients. AB - OBJECTIVE: Inflammatory cytokines as well as nitric oxide (NO) play a key role in the pathogenesis of persistent and exaggerated pain states. To document this, we investigated whether a range of cytokines and NO were detectable in the plasma of chronic pain patients and whether cytokine and NO levels correlated with pain severity. METHODS: Plasma samples of 94 chronic pain patients and 6 healthy volunteers were obtained. Average pain intensity during the last 24 h was assessed on a 11-point numeric rating scale and patients were distributed to three groups: light, moderate and severe pain. The concentrations of TNF-alpha, GM-CSF, interleukin (IL)-1beta, IL-6, IL-8, interferon (IFN)-gamma, IL-2, IL-4, IL-5, IL-10 and nitrate/nitrite were determined. RESULTS: Patients with light pain demonstrated significantly increased levels of IL-6 compared to controls. In the severe pain group IL-6 and nitrate/nitrite were significantly increased. Serum concentrations of IL-1beta, TNF-alpha, IL-2 and IL-4 were increased but as we adjusted the level of significance at p = 0.0045, most cytokine plasma levels failed to reach statistical significance. CONCLUSIONS: Pro-inflammatory cytokines (IL-1beta, IL-2, IL-6, IFN-gamma, TNF-alpha) in the plasma correlate with increasing pain intensity. Chronic pain patients show a significant increase in plasma levels of NO in comparison to healthy controls. PMID- 17334669 TI - Differential immunostimulating effect of granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and interferon gamma (IFNgamma) after severe trauma. AB - OBJECTIVE: Severe trauma leads to an increased vulnerability to bacterial sepsis. In the present study, we compared the immunostimulating potential of granulocyte colony stimulating-factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma). DESIGN: Prospective clinical experimental study. SETTING: University hospital intensive care unit and research facility. PATIENTS: 6 patients with an Injury Severity Score (ISS) of more than 25 points. INTERVENTIONS: Heparinized blood samples of severely injured patients and 12 healthy volunteers were incubated in vitro with 10 ng/ml GM-CSF, 10 ng/ml G-CSF or 10 ng/ml IFN-gamma for 6 h. MEASUREMENTS: Flow cytometry: HLA-DR expression on monocytes, B- and T-lymphocytes. ELISA: LPS-induced TNFalpha and IL 10 production. RESULTS: In all patients reduced cytokine production and HLA-DR expression on monocytes was established. After administration of GM-CSF and IFN gamma it in vitro, the level of HLA-DR expression on monocytes and the it ex vivo TNFalpha-synthesis increased while only GM-CSF increased significantly IL-10 liberation after LPS-stimulation. However, only IFN-gamma had the capacity to enhance HLA-DR on B- and T-lymphocytes. G-CSF it in vitro had no significant effect on the measured parameter. CONCLUSIONS: These data suggest that GM-CSF and IFN-gamma may serve to support immune functions in severely injured patients. PMID- 17334670 TI - Optimized THP-1 differentiation is required for the detection of responses to weak stimuli. AB - OBJECTIVES: The differentiation of THP-1 monocytes into macrophages is mainly conducted at a phorbol 12-myristate 13-acetate (PMA) concentration of 10-400 ng/ml. However, this concentration might be high enough to upregulate the expressions of some genes in differentiated macrophages, which could overwhelm gene expression increases induced by other stimuli. The present study was performed to optimize the PMA concentration required to differentiate monocytes whilst minimizing gene upregulation. METHODS: THP-1 cells were treated with 2.5 100 ng/ml PMA and analyzed for the extent of cell adherence, the surface marker of macrophages, and stable differentiation without undesirable gene upregulation. The stably differentiated THP-1 cells at the minimum PMA concentration were treated with 10 ng/ml LPS or 125 nM amyloid beta (Abeta(1-42)). RESULTS: The treatment of THP-1 with 5 ng/ml PMA was found to be sufficient to induce stable differentiation without undesirable gene upregulation. These macrophages differentiated at 5 ng/ml responded well to secondary weak stimuli like 10 ng/ml LPS or 125 nM of amyloid beta (Abeta(1-42)). CONCLUSIONS: This finding suggests that THP-1 cells are well differentiated by 5 ng/ml PMA, and that the resulting differentiated macrophages respond well to secondary weak stimuli without being overwhelmed by undesirable gene upregulation induced by PMA. PMID- 17334671 TI - Midodrine treatment in the management of severe orthostatic hypotension after hemangioblastoma surgery. PMID- 17334672 TI - Fatal outcome related to carmustine implants in glioblastoma multiforme. AB - Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival. However, some precautions should be taken regarding Gliadel implantation. We report three cases in whom patients with glioblastoma multiforme were implanted with fibrin glue-secured Gliadel after the lateral ventricles had been opened, and who later developed severe hydrocephalus leading to death. Although Gliadel may be an important adjunct to treatment, opening of the ventricles during surgery as part of its application should be considered a contra-indication. PMID- 17334673 TI - Early results from the use of the Lichtenstein repair in the management of strangulated groin hernia. AB - BACKGROUND: Use of prosthetic repairs in the management of strangulated hernias has so far been very limited due to the fear of an associated higher incidence of complications, especially those related to the presence of the mesh. The aim of this study was to prospectively determine whether the use of the Lichtenstein repair in the management of strangulated groin hernias was associated with a higher rate of wound infection and/or mesh-related complications than in the elective setting. PATIENTS AND METHODS: The results obtained from the use of the Lichtenstein repair in the management of 25 patients with strangulated groin hernias (group I) were compared to those of another 25 age- and sex-matched patients undergoing Lichtenstein repair for elective groin hernia repair (group II). RESULTS: In group I, one patient (4%) developed a scrotal hematoma. No other postoperative complications were encountered, whether related or unrelated to the presence of the mesh. No complications were encountered in group II patients. Throughout the 20-month duration of the present study, no mesh had to be removed and no recurrences were encountered in either group. CONCLUSION: The good short term results of the present study in terms of absence of wound infection, mesh related complications and recurrence suggest that use of the Lichtenstein repair in the management of strangulated groin hernias is safe and is not associated with a higher rate of complications compared to its use in the elective setting. PMID- 17334674 TI - Skin pretreatment with an Er:YAG laser promotes the transdermal delivery of three narcotic analgesics. AB - Because of their low oral bioavailabilities and short half-lives, it may be more feasible to administer narcotic analgesics via the skin. However, this delivery method is limited by the low permeability of the stratum corneum (SC). The aim of this study was to enhance the transdermal delivery of three narcotic drugs, including morphine, nalbuphine, and buprenorphine, with an erbium:yttrium aluminum-garnet (Er:YAG) laser pretreatment. In an in vitro pig skin permeation experiment, Er:YAG laser pretreatment of the skin produced a 10~35-fold enhancement in drug permeation that was dependent on the laser fluence and the narcotic analgesic used. The permeation of morphine and nalbuphine showed higher enhancement with Er:YAG laser treatment as compared to that of buprenorphine. This may have been due to the higher lipophilicity and molecular mass of buprenorphine than the other two narcotic drugs. A photomechanical wave was generated by filtering laser radiation through a polystyrene target. The experimental results showed that a single photomechanical wave was sufficient to enhance morphine permeation by sevenfold. This enhancement was significantly lower than that produced by direct laser irradiation, indicating the predominant mechanism of SC ablation by the Er:YAG laser for transdermal drug delivery. PMID- 17334675 TI - Treatment of carpal tunnel syndrome by low-level laser versus open carpal tunnel release. AB - Carpal tunnel syndrome (CTS) is an entrapment neuropathy of the median nerve at the wrist. It is one of the most common peripheral nerve disorders. The cause of idiopathic CTS remains unclear. The diagnosis of CTS is still mainly clinical. Open carpal tunnel release is the standard treatment. The present study was conducted to evaluate the effectiveness of low level laser treatment (LLLT) for CTS in comparison to the standard open carpal tunnel release surgery. Out of 54 patients, 60 symptomatic hands complaining of CTS were divided into two equal groups. Group A, was subjected to LLLT by Helium Neon (He-Ne) laser (632.8 nm), whereas group B was treated by the open approach for carpal tunnel release. The patients were evaluated clinically and by nerve conduction studies (NCSs) about 6 months after the treatment. LLLT showed overall significant results but at a lower level in relation to surgery. LLLT showed significant outcomes in all parameters of subjective complaints (p < or = 0.01) except for muscle weakness. Moreover, LLLT showed significant results in all parameters of objective findings (p < or = 0.01) except for thenar atrophy. However, NCSs expressed the same statistical significance (p < or = 0.01) after the treatment by both modalities. LLLT has proven to be an effective and noninvasive treatment modality for CTS especially for early and mild-to-moderate cases when pain is the main presenting symptom. However, surgery could be preserved for advanced and chronic cases. Refinement of laser tools and introduction of other wavelengths could make LLLT for CTS treatment a field for further investigations. PMID- 17334676 TI - Effects of two types of low-level laser wave lengths (850 and 630 nm) on the orthodontic tooth movements in rabbits. AB - The effects of low-level lasers on bone cellular activity, bone structures, bone healing, fibroblasts activity and inflammation process have already been investigated. Considering orthodontic tooth movement, which is a complicated inflammatory process involving simultaneous bone apposition and resorption, the aim of this controlled study is to investigate the quantitative effects of a pulsed 850 nm laser (Optodan) and a continuous 630 nm laser (KLO3) on the orthodontic tooth movement in rabbits. This experimental study was conducted on 18 male albino rabbits divided into three equal groups of control, Optodan and KLO3. In all the groups, NiTi-closed coil springs were used on the first mandibular molars with 4-oz tension. The control group was not irradiated by laser, but the teeth in the laser groups were irradiated 9 days according to the periodontal therapeutic protocols. After 16 days, samples were sacrificed. The distance between the distal surface of the first molar and the mesial surface of the second molar was measured with 0.05-mm accuracy. The data were subjected to the statistical tests of Kolmogrov Smirnov and variance analysis. The mean orthodontic tooth movements of the first mandibular molars were 1.7 +/- 0.16 mm in control group, 0.69 +/- 0.16 mm in Optodan group and 0.86 +/- 0.13 mm in KLO3 group. There were statistically significant difference between the control and the two other laser-irradiated groups (P < 0.001). The findings of the present study imply that the amounts of orthodontic tooth movement, after low-level laser therapy, are diminished. It could not be concluded that any low-level laser will reduce the speed of teeth movement in orthodontic treatments, and further studies with less or more energies may show different results. PMID- 17334677 TI - The importance of coherence length in laser phototherapy of gingival inflammation: a pilot study. AB - The aim of this study was to investigate if coherence length is of importance in laser phototherapy. Twenty patients with moderate periodontitis were selected. After oral hygiene instructions, scaling and root planing (SRP), one side of the upper jaw was randomly selected for HeNe (632.8 nm, 3 mW) or InGaAlP (650 nm, 3 mW) laser irradiation. One week after SRP, the following parameters were measured: pocket depth, gingival index, plaque index, gingival crevicular fluid volume, matrix metalloproteinase (MMP-8), interleukin (IL-8) and subgingival microflora. The irradiation (180 s per point, energy 0.54 J) was then performed once a week for 6 weeks. At the follow up examination, all clinical parameters had improved significantly in both groups. A more pronounced decrease of clinical inflammation was observed after HeNe treatment. MMP-8 levels were considerably reduced on the HeNe side, while there was no difference for IL-8 or microflora. Coherence length appears to be an important factor in laser phototherapy. PMID- 17334679 TI - Comment on Schott et al.: which screening strategy using BMD measurements would be most cost effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model. PMID- 17334680 TI - A novel method for visualization of entire coronary arterial tree. AB - The complexity of the coronary circulation especially in the deep layers largely evades experimental investigations. Hence, virtual/computational models depicting structure-function relation of the entire coronary vasculature including the deep layer are imperative. In order to interpret such anatomically based models, fast and efficient visualization algorithms are essential. The complexity of such models, which include vessels from the large proximal coronary arteries and veins down to the capillary level (3 orders of magnitude difference in diameter), is a challenging visualization problem since the resulting geometrical representation consists of millions of vessel segments. In this study, a novel method for rendering the entire porcine coronary arterial tree down to the first segments of capillaries interactively is described which employs geometry reduction and occlusion culling techniques. Due to the tree-shaped nature of the vasculature, these techniques exploit the geometrical topology of the object to achieve a faster rendering speed while still handling the full complexity of the data. We found a significant increase in performance combined with a more accurate, gap less representation of the vessel segments resulting in a more interactive visualization and analysis tool for the entire coronary arterial tree. The proposed techniques can also be applied to similar data structures, such as neuronal trees, airway structures, bile ducts, and other tree-like structures. The utility and future applications of the proposed algorithms are explored. PMID- 17334681 TI - Electromagnetic power absorption and temperature changes due to brain machine interface operation. AB - To fully understand neural function, chronic neural recordings must be made simultaneously from 10s or 100s of neurons. To accomplish this goal, several groups are developing brain machine interfaces. For these devices to be viable for chronic human use, it is likely that they will need to be operated and powered externally via a radiofrequency (RF) source. However, RF exposure can result in tissue heating and is regulated by the FDA/FCC. This paper provides an initial estimate of the amount of tissue heating and specific absorption rate (SAR) associated with the operation of a brain-machine interface (BMI). The operation of a brain machine interface was evaluated in an 18-tissue anatomically detailed human head mesh using simulations of electromagnetics and bio-heat phenomena. The simulations were conducted with a single chip, as well as with eight chips, placed on the surface of the human brain and each powered at four frequencies (13.6 MHz, 1.0 GHz, 2.4 GHz, and 5.8 GHz). The simulated chips consist of a wire antenna on a silicon chip covered by a Teflon dura patch. SAR values were calculated using the finite-difference time-domain method and used to predict peak temperature changes caused by electromagnetic absorption in the head using two-dimensional bio-heat equation. Results due to SAR alone show increased heating at higher frequencies, with a peak temperature change at 5.8 GHz of approximately 0.018 degrees C in the single-chip configuration and 0.06 degrees C in the eight-chip configuration with 10 mW of power absorption (in the human head) per chip. In addition, temperature elevations due to power dissipation in the chip(s) were studied. Results show that for the neural tissue, maximum temperature rises of 3.34 degrees C in the single-chip configuration and 7.72 degrees C in the eight-chip configuration were observed for 10 mW dissipation in each chip. Finally, the maximum power dissipation allowable in each chip before a 1.0 degrees C temperature increase (most stringent standards as denoted in the FDA guidelines) is exceeded in the head was simulated and found to be 2.92 mW in the single-chip configuration and 1.25 mW in the eight-chip configuration. As thermal heating due to SAR was insignificant, this study suggests that wireless electromagnetics, i.e., RF may be a viable option for powering, and communicating with brain machine interfaces for clinical applications. PMID- 17334682 TI - Estrogen regulation and ion dependence of taurine uptake by MCF-7 human breast cancer cells. AB - It has been reported that estrogen receptor-positive MCF-7 cells express TauT, a Na(+)-dependent taurine transporter. However, there is a paucity of information relating to the characteristics of taurine transport in this human breast cancer cell line. Therefore, we have examined the characteristics and regulation of taurine uptake by MCF-7 cells. Taurine uptake by MCF-7 cells showed an absolute dependence upon extracellular Na(+). Although taurine uptake was reduced in Cl(-) free medium a significant portion of taurine uptake persisted in the presence of NO(3) (-). Taurine uptake by MCF-7 cells was inhibited by extracellular beta alanine but not by L-alanine or L-leucine. 17beta-estadiol increased taurine uptake by MCF-7 cells: the V(max) of influx was increased without affecting the K(m). The effect of 17beta-estradiol on taurine uptake by MCF-7 cells was dependent upon the presence of extracellular Na(+). In contrast, 17beta-estradiol had no significant effect on the kinetic parameters of taurine uptake by estrogen receptor-negative MDA-MB-231 cells. It appears that estrogen regulates taurine uptake by MCF-7 cells via TauT. In addition, Na(+)-dependent taurine uptake may not be strictly dependent upon extracellular Cl(-). PMID- 17334683 TI - Ultracentrifugation studies of the location of the site involved in the interaction of pig heart lactate dehydrogenase with acidic phospholipids at low pH. A comparison with the muscle form of the enzyme. AB - Lactate dehydrogenase (LDH) from the pig heart interacts with liposomes made of acidic phospholipids most effectively at low pH, close to the isoelectric point of the protein (pH = 5.5). This binding is not observed at neutral pH or high ionic strength. LDH-liposome complex formation requires an absence of nicotinamide adenine dinucleotides and adenine nucleotides in the interaction environment. Their presence limits the interaction of LDH with liposomes in a concentration-dependent manner. This phenomenon is not observed for pig skeletal muscle LDH. The heart LDH-liposome complexes formed in the absence of nicotinamide adenine dinucleotides and adenine nucleotides are stable after the addition of these substances even in millimolar concentrations. The LDH substrates and studied nucleotides that inhibit the interaction of pig heart LDH with acidic liposomes can be ordered according to their effectiveness as follows: NADH > NAD > ATP = ADP > AMP > pyruvate. The phosphorylated form of NAD (NADP), nonadenine nucleotides (GTP, CTP, UTP) and lactate are ineffective. Chemically cross-linked pig heart LDH, with a tetrameric structure stable at low pH, behaves analogously to the unmodified enzyme, which excludes the participation of the interfacing parts of subunits in the interaction with acidic phospholipids. The presented results indicate that in lowered pH conditions, the NADH-cofactor binding site of pig heart LDH is strongly involved in the interaction of the enzyme with acidic phospholipids. The contribution of the ATP/ADP binding site to this process can also be considered. In the case of pig skeletal muscle LDH, neither the cofactor binding site nor the subunit interfacing areas seem to be involved in the interaction. PMID- 17334685 TI - Structure and fragmentation in colloidal artificial molecules and nuclei. AB - Motivated by recent experiments on colloidal systems with competing attractive and repulsive interactions, we simulate a two-dimensional system of colloids with competing interactions that can undergo fragmentation. In the absence of any other confining potential, the colloids can form stable clusters depending on the strength of the short range attractive term. By suddenly changing the strength of one of the interaction terms we find a rich variety of fragmentation behavior which is affected by the existence of "magic" cluster numbers. Such soft matter systems can be used to construct artificial nuclei. PMID- 17334684 TI - Internal structure of magnetic endosomes. AB - The internal structure of biological vesicles filled with magnetic nanoparticles is investigated using the following complementary analyses: electronic transmission microscopy, dynamic probing by magneto-optical birefringence and structural probing by Small Angle Neutron Scattering (SANS). These magnetic vesicles are magnetic endosomes obtained via a non-specific interaction between cells and anionic magnetic iron oxide nanoparticles. Thanks to a magnetic purification process, they are probed at two different stages of their formation within HeLa cells: (i) adsorption of nanoparticles onto the cellular membrane and (ii) their subsequent internalisation within endosomes. Differences in the microenvironment of the magnetic nanoparticles at those two different stages are highlighted here. The dynamics of magnetic nanoparticles adsorbed onto cellular membranes and confined within endosomes is respectively 3 and 5 orders of magnitude slower than for isolated magnetic nanoparticles in aqueous media. Interestingly, SANS experiments show that magnetic endosomes have an internal structure close to decorated vesicles, with magnetic nanoparticles locally decorating the endosome membrane, inside their inner-sphere. These results, important for future biomedical applications, suggest that multiple fusions of decorated vesicles are the biological processes underlying the endocytosis of that kind of nanometric materials. PMID- 17334686 TI - Granular flows in a rotating drum: the scaling law between velocity and thickness of the flow. AB - The flow of dry granular material in a half-filled rotating drum is studied. The thickness of the flowing zone is measured for several rotation speeds, drum sizes and beads sizes (size ratio between drum and beads ranging from 47 to 7400). Varying the rotation speed, a scaling law linking mean velocity vs. thickness of the flow, v approximately h(m), is deduced for each couple (beads, drum). The obtained exponent m is not always equal to 1, the value previously reported for a drum in litterature, but varies with the geometry of the system. For small size ratios, exponents higher than 1 are obtained due to a saturation of the flowing zone thickness. The exponent of the power law decreases with the size ratio, leading to exponents lower than 1 for high size ratios. These exponents imply that the velocity gradient of a dry granular flow in a rotating drum is not constant. More fundamentally, these results show that the flow of a granular material in a rotating drum is very sensible to the geometry, and that the deduction of the "rheology" of a granular medium flowing in such a geometry is not obvious. PMID- 17334687 TI - Kinetics of protein-release by an aptamer-based DNA nanodevice. AB - A recently introduced DNA nanodevice can be used to selectively bind or release the protein thrombin triggered by DNA effector strands. The release process is not well described by simple first or second order reaction kinetics. Here, fluorescence resonance energy transfer and fluorescence correlation spectroscopy experiments are used to explore the kinetics of the release process in detail. To this end the influence of concentration variations and also of temperature is determined. The relevant kinetic parameters are extracted from these experiments and the kinetic behavior of the system is simulated numerically using a set of rate equations. The hydrodynamic radii of the aptamer device alone and bound to thrombin are determined as well as the dissociation constant for the aptamer device-thrombin complex. The results from the experiments and a numerical simulation support the view that the DNA effector strand first binds to the aptamer device followed by the displacement of the protein. PMID- 17334688 TI - Polymerization of 2-methylaniline and 2-methoxyaniline in water/pentane biphasic system. AB - We report on chemical polymerization of two aniline derivatives - 2-methylaniline and 2-methoxyaniline -- in a two-phase water/pentane system. We have found that poly(2-methylaniline) is produced in form of an amorphous material regardless of the fact whether the monomer is initially dissolved in aqueous or organic phase. The behavior of 2-methoxyaniline is significantly different. The oxidation of this monomer generally results in formation of a water soluble oligomer and an insoluble polymeric product. In consequence, depending on the experimental setup, the polymer is prepared in form of a thin film at the organic/aqueous interface or as micrometer-sized spherical particles dispersed in the aqueous phase. PMID- 17334689 TI - Particle structuring under the effect of an uniaxial deformation in soft/hard nanocomposites. AB - A model nanocomposite sample, made of rigid monodisperse spherical inclusions in a deformable matrix, was uniaxially stretched. The displacement field of the particles at the sample surface is analyzed using atomic force microscopy. It is shown that its 2D structure factor presents most of the characteristic features previously described from scattering experiments on similar materials. At the scale of the particles, distortions from affinity are observed. They can be explained by the radial interactions between neighboring inclusions, related to the mechanical confinement of the matrix between particles. At larger scales, remarkable alignments of particles are observed along a direction which is roughly perpendicular to the stretching direction. We show that this effect is found in other soft/hard nanocomposites. It may contribute to the mechanical properties of this class of heterogeneous materials. PMID- 17334690 TI - Electro-optic characterization of a nematic phase formed by bent core mesogens. AB - The purpose of this paper is the demonstration that bent core nematic phases behave quantitatively and qualitatively very different from ordinary calamitic nematics in their electro-optical characteristics. We present measurements of the elastic properties from the analysis of Brochard-Leger walls that are formed during the splay Freedericksz transition in sandwich cells. These walls possess an unusually large shape anisotropy as compared to similar structures in calamitic nematics. The wall shapes can be explained when one assumes that the bend elastic constant K(33) is one order of magnitude larger than the twist constant K(22) of the material, supposing that flexoelectricity in the description of the elastic deformations can be neglected. Further we report periodic structures above the splay Freedericksz transition with a wave vector perpendicular to the director easy axis. They represent either a static instability or an unconventional type of electrically driven convection. PMID- 17334691 TI - Performance of laser bonded glass/polyimide microjoints in cerebrospinal fluid. AB - In this paper, laser bonded microjoints between glass and polyimide is considered to examine their potential applicability in encapsulating neural implants. To facilitate bonding between polyimide and glass, a thin titanium film with a thickness of 2 microm was deposited on borosilicate glass plates by a physical vapor deposition (PVD) process. Titanium coated glass was then joined with polyimide by using a cw fiber laser emitting at a wavelength of 1.1 microm (1.0 W) to prepare several tensile samples. Some of the samples were exposed to artificial cerebrospinal fluid (aCSF) at 37 degrees C for two weeks to assess long-term integrity of the joints. Both the as-received and aCSF soaked samples were subjected to uniaxial tensile loads for bond strengths measurements. The bond strengths for the as-received and aCSF soaked samples were measured to be 7.31 and 5.33 N/mm, respectively. Although the long-term exposure of the microjoints to aCSF has resulted in 26% reduction of bond strength, the samples still retain considerably high strength as compared with the titanium-polyimide samples. The failed glass/polyimide samples were also analyzed using optical microscopy, and failure mechanisms are discussed. In addition, a two dimensional finite element analysis (FEA) was conducted to understand the stress distribution within the substrate materials while the samples are in tension. The FEA results match reasonably well with the experimental load-displacement curves for as received samples. Detailed discussion on various stress contours is presented in the paper, and the failure mechanisms observed from the experiment are shown in good agreement with the FEA predicted ones. PMID- 17334692 TI - Investigation for analytical procedure for determination of trace metallic ions in simulated body fluids by inductively coupled plasma atomic emission spectrometry (ICP-AES). AB - Influences of matrix elements and high viscosity in three kind of simulated body fluids (SBFs) on determination of trace metallic elements (Co, Cr, Ni, Al and V) by inductively coupled plasma atomic emission spectrometry (ICP-AES) were investigated. In addition, decreases of these effects were attempted by H(2)SO(4) fume treatment. Calibration lines of the elements were constructed by the standard solutions made of elemental solutions and HCl or the SBFs. Gradients of calibration lines constructed by the each standard solution were different. Therefore, for accurate determination, calibration curve must be constructed by the elemental standard solution and the analytical solution. Limit of detection (LOD) of each element in the solutions was measured by a blank test. Although LODs of microg [Symbol: see text] L(-1) (ppb) order were nominal instrumental data, because of influences of the matrix elements and the high viscosity, the measured LODs of the elements in the SBFs were higher than those. However, the LODs were lowered by employing the H(2)SO(4)-fume treatment and approached to the nominal instrumental data. Therefore, H(2)SO(4)-fume treatment is extremely effective treatment in order to reduce the influences. PMID- 17334693 TI - Ion implantation modified stainless steel as a substrate for hydroxyapatite deposition. Part I. Surface modification and characterization. AB - Material surfaces play critical role in biology and medicine since most biological reactions occur on surfaces and interfaces. There are many examples showing that the surface properties of the materials control and are directly involved in biological reactions and processes in-vitro like blood compatibility, protein absorption, cell development, etc. The rules that govern the diversity of biological surface phenomenon are fundamental physical laws. Stainless steel doped with Cr, Ni and Mo is widely used material in medicine and dentistry due to its excellent corrosion resistance and mechanical properties. The interest in this material has stimulated extensive studies on improving its bone-bonding properties. This paper describes the surface modification of Cr-Ni stainless steel (AISI 316) by a whole surface sequential implantation of Ca and P ions (the basic ions of hydroxyapatite). Three groups of stainless steel samples are prepared: (i) ion-implanted, (ii) ion-implanted and thermally treated at 600( composite function)C in air for 1 h and (iii) initials. The surface chemistry and topography before and after the surface modification are characterized by X-ray photoelectron spectroscopy, Auger electron spectroscopy, magic mirror method, atomic force microscopy and contact angle measurements. PMID- 17334694 TI - Ion implantation modified stainless steel as a substrate for hydroxyapatite deposition. Part II. Biomimetic layer growth and characterization. AB - The interest in stainless steel as a material widely used in medicine and dentistry has stimulated extensive studies on improving its bone-bonding properties. AISI 316 stainless steel is modified by a sequential ion implantation of Ca and P ions (the basic ions of hydroxyapatite), and by Ca and P implantation and subsequent thermal treatment in air (600( composite function)C, 1 h). This paper investigates the ability of the as-modified surfaces to induce hydroxyapatite deposition by using a biomimetic approach, i.e. immersion in a supersaturated aqueous solution resembling the human blood plasma (the so-called simulated body fluid). We describe our experimental procedure and results, and discuss the physico-chemical properties of the deposed hydroxyapatite on the modified stainless steel surfaces. It is shown that the implantation of a selected combination of ions followed by the applied methodology of the sample soaking in the simulated body fluid yield the growth of hydroxyapatite layers with composition and structure resembling those of the bone apatite. The grown layers are found suitable for studying the process of mineral formation in nature (biomineralization). PMID- 17334695 TI - Synthesis, characterization and hydrolytic degradation of degradable poly(butylene terephthalate)/poly(ethylene glycol) (PBT/PEG) copolymers. AB - Hydrolytic degradable PBT/PEG copolymer was synthesized by macromolecular transesterification method from PBT and PEG macromonomers. The resultant copolymers were characterized by (1)H-NMR and GPC. The non-isothermal crystallization behavior of these copolymers was studied by differential scanning calorimetry (DSC). The water absorption and hydrolytic degradation behavior of PBT/PEG copolymers were also studied in detail. PMID- 17334696 TI - Formation mechanism of biomedical apatite coatings on porous titania layer. AB - A titania containing calcium and phosphate with rough and porous structure was prepared by microarc oxidation. The in vitro bioactivity was examined by immersing the samples into the simulated body fluid (SBF). And the mechanism was also discussed. The results show that only 3 days of immersion in SBF, apatite was formed on the surface, and after 6 days, nearly all the surface covered by apatite. This indicates that the layer can induce the formation of apatite in simulated body fluid. It is analyzed that the key factors of the apatite formation are the hydrolysis of the CaTiO(3) and special structure. PMID- 17334697 TI - The influence of implant surface properties on cell adhesion and proliferation. AB - Interactions of the foreign material of implant and the living tissue on the cell level can cause prolonged healing or, worse, loss of the implant. The cell response to the presence of some implant materials was studied under in vitro conditions. The influence of physicochemical surface parameters on the response of the cells in the immediate vicinity of implants, namely on adhesion, proliferation and synthetic activity of fibroblasts, and on the blood coagulation were compared. The direct contact of tested materials (titanium and Ti6Al4V alloy with various surface treatments, Cr Co Mo alloy, hydroxyapatite-coated titanium, zirconium oxide ceramics, polyethylene and carbon composite) on cell spreading was monitored and the presence of TNF-alpha and IL-8 was evaluated in the cultivation medium. The formation of blood clots was investigated on samples immersed in a well with freshly drawn whole rabbit blood using a scanning electron microscope. The surface free energy was estimated using the measurement of static contact angle. Both the advancing and receding contact angles were measured by the dynamic Wilhemy plate method. Two main groups with extremes in cell viability were established. In the first group the increased polar component of surface free energy, the highest cell density, the lowest inflammatory cytokine production, but no fibres in the clotting blood were found. On the contrary, the second group of materials with a very low polar component of the surface free energy showed distinctly higher expression of inflammatory mediators, low cell proliferation, but faster formation of fibres in the blood coagulum. PMID- 17334698 TI - Preparation and characterization of biodegradable anti-adhesive membrane for peritoneal wound healing. AB - Postoperative adhesions remain a significant complication of abdominal surgery although the wide variety of physical barriers has been developed to reduce the incidence of adhesion. In this study, the bilayered composite membrane formed by the association of a methoxy poly (ethylene glycol)-poly (L-lactide-co-glycolide) (mPEG-PLGA) film and a crosslinked collagen-hyaluronic acid (Col-HA) membrane with fibronectin (FN) coating was prepared for promoting wound healing and providing tissue adhesion resistance simultaneously. In vitro adhesion test revealed that fibroblasts attached better on Col-HA membrane compared to those on mPEG-PLGA film, PLGA film or Interceed (oxidized cellulose) while mPEG-PLGA film had the lowest cell adhesive property. In confocal microscopic observation, the actin filaments were significantly further polymerized when 50 or 100 microg/cm(3) fibronectin was incorporated on the COL-HA membranes. After 7-day culture, fibroblasts penetrated throughout the Col-HA-FN network and the cell density increased whereas very few cells were found attached on the surface of the mPEG-PLGA film. In vivo evaluation test showed that the composite membrane could remain during the critical period of peritoneal healing and did not provoke any inflammation or adverse tissue reaction. PMID- 17334699 TI - Cross-section transmission electron microscopy characterization of the near surface structure of medical Nitinol superelastic tubing. AB - The application of Nitinol in a wide variety of medical implants is progressively increasing because of its unique mechanical properties, durability and biocompatibility. However, as Nitinol consists of about 50 at.% of toxic Ni, certain applications are still hindered by the concern of free Ni release in the surrounding tissue. The latter is controlled by the structure of near-surface layers and can be strongly affected by various surface treatments. A proper application of advanced cross-section sample preparation techniques allows us to characterize the Nitinol near-surface structure down to the nanoscale by means of transmission electron microscopy (TEM). Elemental maps of the Ti, O and Ni distribution, concentration profiles, quantification of composition as well as atomic resolution images at the surface of a Nitinol tubing are presented and the results obtained with different sample preparation and analytical characterization techniques are compared. In addition to a strong decrease of Ni towards the surface of the oxide layer and a Ti depleted layer underneath the oxide, also a possible transformation from TiO to TiO(2) is documented. PMID- 17334700 TI - Biocompatibility of diamond-like nanocomposite thin films. AB - Diamond-like nanocomposite (DLN) films consist of network structure of amorphous carbon and quartz like silicon. In the present work, DLN films have been synthesized on pyrex glass and subsequently, their biocompatibility have been investigated through primary and secondary cell adhesion, cytotoxicity, protein adsorption and murine peritoneal macrophage activation experiments. Variable degree of cell and protein response have been found based on variable film synthesis parameters but in overall, required biocompatibility has been established for all types of film-coating. PMID- 17334701 TI - Preparation and bioactivity of novel multiblock thermoplastic elastomer/tricalcium phosphate composites. AB - There is a recognized need for improved treatment of osteoarthritis of the finger joints disease. Joint fusions are commonly used for treating the pain and potential deformity of arthritis. At severe deformity, artificial joint replacement is required. The most widely used are space-filler type joints made of high performance silicone rubber. One of the problems that occurs with these artificial replacements is that they can fail, because silicone elastomer used for their fabrication is relatively weak material and show to break apart and fragment. We have recently developed novel poly(aliphatic/aromatic-ester) (PED) material of sufficient mechanical properties and excellent flexibility. To enhance the bioactivity of these polymers (PED) and bone-bonding properties, PED/beta-TCP composites were prepared. The ceramic particles were homogeneously distributed during conventional blending and showed good adhesion to the polymer matrix. The thermal characteristics and mechanical properties of the composites were investigated as a function of beta-TCP content. The Youngs modulus and the yield strength of the composites increased with the increase in beta-TCP volume while the tensile strength and fracture strain decreased. In vitro investigations demonstrated an increase in cytocompatibility with increasing amount of beta-TCP up to 20 vol%. PMID- 17334702 TI - Structure and dissolution investigation of calcium-bismuth-borate glasses and vitroceramics containing silver. AB - Quaternary Ag(2)O-CaO-Bi(2)O(3)-B(2)O(3) glasses and glassceramics are investigated with regard to release behaviour and local structure. The dissolution behaviour in water and physiological serum shows that the cations are released rapidly or gradually and points out a multi-step process, generally characterised by higher rates in water than in physiological serum. The structural effect of silver addition to bismuth-borate glasses is observed from infrared spectroscopic data. The antibacterial activity of the investigated samples was tested on six bacterial media. PMID- 17334703 TI - Subacute systemic toxicity assessment of beta-tricalcium phosphate/carboxymethyl chitin composite implanted in rat femur. AB - The efficacy of a composite of beta-tricalcium phosphate particles and carboxymethyl-chitin (beta-TCP/CM-chitin) for bone repair has already been established in animal experiments. In the present study, subacute systemic toxicity was evaluated to further assess the biological safety of the implanted composite. beta-TCP/CM-chitin (approximately 4 mg/kg and 7 mg/kg in male and female rats, respectively) was implanted for 28 days into penetrating defects (2 mm diameter) made artificially in the shaft of the right femur of rats. Sham operation groups with the defect only were prepared as controls. Haematology, blood chemistry, urinalysis, and the histopathology of 44 organs and tissues were investigated. Body weight measurements and clinical observations were performed daily throughout the study. No subacute systemic toxicity possibly caused by the implantation of beta-TCP/CM-chitin was detected. These findings indicate that beta-TCP/CM-chitin composite is a highly biocompatible bone substitute, at least with an implantation dosage of < 4-7 mg/kg. PMID- 17334704 TI - Calculation of heating power generated from ferromagnetic thermal seed (PdCo-PdNi CuNi) alloys used as interstitial hyperthermia implants. AB - High quality heating device made of ferromagnetic alloy (thermal seed) was developed for hyperthermia treatment of cancer. The device generates sufficient heat at room temperature and stops heating at the Curie temperature T (c). The power dissipated from each seed was calculated from the area enclosed by the hysteresis loop. A new mathematical formula for the calculation of heating power was derived and showed good agreement with those calculated from hysteresis loop and calorimetric method. PMID- 17334705 TI - Preliminary investigation of bioactivity of nano biocomposite. AB - Bioactive biomaterials can form a bone-like apatite layer on their surfaces in the body, which is critical to establishing bone bonding between bioactive materials and living tissue. At present study, the bone-like apatite formation in vitro and vivo on the surface of the nano apatite/polyamide composite was studied, and the bioactive composites implanted into the femora of rabbits were also investigated. The results revealed that the bone-like apatite containing carbonate can form on the surface of the biocomposite both in SBF and dorsal muscle of rabbits, and the composite would form directly combination with the natural bone without fibrous capsule tissue between implant and host bone tissue. All of these indicated that the nano biocomposites have excellent bioactivity and can be used for bone replacement. PMID- 17334706 TI - Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine. AB - Large neutral amino acids (LNAA) 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 an open-label study using LNAA, a surprising decline of blood Phe concentration was found in patients with PKU in metabolic treatment centres in Russia, the Ukraine, and the United States. To validate the data obtained from this trial, a short-term double-blind placebo control study was done using LNAA in patients with PKU, with the participation of three additional metabolic centres--Milan, Padua and Rio de Janeiro. The results of the short trial showed significant lowering of blood Phe concentration by an average of 39% from baseline. The data from the double-blind placebo control are encouraging, establishing proof of principle of the role of orally administered LNAA in lowering blood Phe concentrations in patients with PKU. Long-term studies will be needed to validate the acceptability, efficacy and safety of such treatment. PMID- 17334707 TI - Estimation of the total number of disease-causing mutations in ornithine transcarbamylase (OTC) deficiency. Value of the OTC structure in predicting a mutation pathogenic potential. AB - Ornithine transcarbamylase deficiency (OTCD), the X-linked, most frequent urea cycle error, results from mutations in the OTC gene, encoding a 354-residue polypeptide. To date 341 OTCD clinical mutations, including 222 missense single nucleotide changes (mSNCs), have been compiled (Hum Mutat 2006;27:626). OTCD mutation detection might be simplified if the entire repertoire of OTCD-causing mutations were known. We estimate the size of this repertoire from 23 new OTCD patients exhibiting 22 different mutations, of which 9, including 4 mSNCs, are novel. The complete repertoire of OTCD-causing mutations is estimated as 560 mutations (95% confidence interval, 422-833 mutations), including 290 mSNCs (95% confidence interval, 230-394 mSNCs). Thus, OTCD diagnosis based on the screening for known mutations might attain 90% sensitivity in <5 years. Since disease causing mSNCs represent <20% of the 2064 possible OTC mSNCs, simple approaches are essential for discrimination between causative and trivial mSNCs. Observation of the OTC structure appears a simple approach for such discrimination, comparing favourably in our sample with three formalized structure-based and/or sequence based in silico assessment methods, and supporting the causation of complete deficiency by the mutations p.Pro305Arg and p.Ser96Phe, and of partial deficiency by p.Asp41Gly, p.Glu122Gly, p.Leu179Phe, p.Pro220Thr and p.Glu273del. Five non mSNC novel mutations (p.Gly71X, a 7-nucleotide and a 10-nucleotide duplication and deletion in exon 5, G>A transitions at bases +1 and +5 of introns 4 and 9, respectively) are obviously pathogenic. The previously reported mSNCs p.Arg26Gln, p.Arg40His, p.Glu52Lys, pLys88Asn, p.Arg129His, p.Asn161Ser, p.Thr178Met, p.His202Tyr, p.Ala208Thr and p.His302Arg, found in our cohort, are also discussed. PMID- 17334708 TI - Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase. AB - Massive urinary excretion of xanthurenic acid, 3-hydroxykynurenine and kynurenine, known as xanthurenic aciduria or hydroxykynureninuria, in a young Somali boy suggested kynureninase deficiency. Mutation analysis of KYNU encoding kynureninase of the index case revealed homozygosity for a c.593 A > G substitution leading to a threonine-to-alanine (T198A) shift. A younger brother was found to have a similar excretion pattern and the same genotype. At present, neither of the two boys has symptoms of niacin deficiency. This is the first report linking xanthurenic aciduria to a mutation in the gene encoding kynureninase. PMID- 17334709 TI - Ras-like small GTPases form a large family of proteins in the marine sponge Suberites domuncula. AB - Sponges (Porifera) are the simplest and the most ancient metazoan animals, which branched off first from the common ancestor of all multicellular animals. We have inspected approximately 13,000 partial cDNA sequences (ESTs) from the marine sponge Suberites domuncula and have identified full or partial cDNA sequences coding for approximately 50 different Ras-like small GTPases. Forty-four sponge proteins from the Ras family are described here: 6 proteins from the Ras subfamily, 5 from Rho, 6 from Arf, 1 Ran, and 26 Rabs or Rab-like proteins. No isoforms of these proteins were detected; the closest related proteins are two Rho proteins with 74% identity. Small GTPases from sponge display a higher degree of sequence conservation with orthologues from vertebrates (53%-93% identity) than with those from either Caenorhabditis elegans or Drosophila melanogaster. The real number of small GTPases in this sponge is certainly much higher than 50, because the actual S. domuncula database of approximately 13,000 ESTs contains at most 3000 nonredundant cDNA sequences. The number of genes for Ras-like small GTPases in yeast, C. elegans, D. melanogaster, and humans is 30, 56, 90, and 174, respectively. Both model invertebrates have only 29 Rabs or Rab-like proteins, compared with 26 already found in sponge, and are missing at least 1 Rab (Rab24) present in S. domuncula and mammals. Our results indicate that duplications and diversifications of genes encoding Ras-like small GTPases, especially the Rab subfamily of small GTPases, happened very early in the evolution of Metazoa. PMID- 17334710 TI - Phylogenetic analysis of antibiotic glycosyltransferases. AB - Catalyzed by a family of enzymes called glycosyltransferases, glycosylation reactions are essential for the bioactivities of secondary metabolites such as antibiotics. Due to the special characters of antibiotic glycosyltransferases (AGts), antibiotics can function by attaching some unusual deoxy-sugars to their aglycons. Comprehensive similarity searches on the amino acid sequences of AGts have been performed. We reconstructed the molecular phylogeny of AGts with neighbor-joining, maximum-likelihood, and Bayesian methods of phylogenetic inference. The phylogenetic trees show a distinct separation of polyene macrolide (PEM) AGts and other polyketide AGts. The former are more like eukaryotic glycosyltransferases and were deduced to be the results of horizontal gene transfer from eukaryotes. Protein tertiary structural comparison also indicated that some glycopeptide AGts (Gtf-proteins) have a close evolutionary relationship with MurGs, essential glycosyltransferases involved in maturation of bacterial cell walls. The evolutionary relationship of glycopeptide antibiotic biosynthetic gene clusters was speculated according to the phylogenetic analysis of Gtf proteins. Considering the fact that polyketide AGts and Gtf-proteins are all GT Family 1 members and their aglycon acceptor biosynthetic patterns are very similar, we deduced that AGts and the synthases of their aglycon acceptors have some evolutionary relevance. Finally, the evolutionary origins of AGts that do not fall into GT Family 1 are discussed, suggesting that their ancestral proteins appear to be derived from various proteins responsible for primary metabolism. PMID- 17334711 TI - Endoscopic resection of early gastric cancer. AB - The purpose of this review is to examine recent advances in the techniques and technologies of endoscopic resection of early gastric cancer (EGC). Endoscopic mucosal resection (EMR) of EGC, with negligible risk of lymph node metastasis, is a standard technique in Japan and is increasingly becoming accepted and regularly used in Western countries. EMR is a minimally invasive technique which is safe, convenient, and efficacious; however, it is insufficient when treating larger lesions. The evidence suggests that difficulties with the correct assessment of depth of tumor invasion lead to an increase in local recurrence with standard EMR when lesions are larger than 15 mm. A major factor contributing to this increase in local recurrence relates to lesions being excised piecemeal due to the technical limitations of standard EMR. A new development in endoscopic techniques is to dissect directly along the submucosal layer -- a procedure called endoscopic submucosal dissection (ESD). This allows the en-bloc resection of larger lesions. ESD is not necessarily limited by lesion size and it is predicted to replace conventional surgery in dealing with certain stages of ECG. However, it still has a higher complication rate when compared to standard EMR, and it requires high levels of endoscopic skill and experience. Endoscopic techniques, indications, pathological assessment, and methods of endoscopic resection of EGC need to be established for carrying out appropriate treatment and for the collation of long-term outcome data. PMID- 17334712 TI - Vascular endothelial growth factor and endoglin (CD-105) in gastric cancer. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. Additionally, CD-105 (endoglin) was proposed as a marker of neovascularization in solid malignancies. The aim of the present study was to (1) evaluate the VEGF and CD-105 expression in gastric carcinoma, (2) determine the role of VEGF gene sequence variations in VEGF expression in gastric carcinoma, and (3) correlate the results of VEGF and CD-105 expression with other standard prognostic parameters, such as size, grade, stage of the disease, metastases, and patient survival. METHODS: VEGF and CD-105 expression were evaluated in 100 unrelated gastric cancer patients using immunohistochemistry. For the genotyping, DNA was isolated from the blood of the gastric cancer patients and from 100 healthy individuals. The genotyping was performed by polymerase chain-restriction fragment length polymorphism analysis. RESULTS: VEGF protein was strongly expressed in the cytoplasm of 36% of the gastric carcinoma samples tested. In all cases, high VEGF expression was accompanied with high endoglin expression. Our results revealed no statistical significant association of any VEGF gene polymorphism with the VEGF and endoglin expression. The correlation of VEGF/CD 105 expression with the clinicopathological parameters of gastric cancer showed that the high expression of VEGF/CD015 was correlated only with lymph node metastasis (P = 0.028). The Kaplan-Meier survival curves have shown a clear association of overall survival after diagnosis of gastric cancer with high VEGF, as well as high CD-105 expression. CONCLUSION: Our results support that VEGF and CD-105 are closely relevant to lymph node metastasis and act as two valuable indicators of prognosis. PMID- 17334713 TI - Prognostic significance of peritoneal washing cytology in Thai patients with gastric adenocarcinoma undergoing curative D2 gastrectomy. AB - BACKGROUND: The aim of the present study was to determine the prognostic significance of peritoneal washing cytology (PWC) among Thai patients with gastric adenocarcinoma. METHODS: Medical charts of 97 patients with gastric adenocarcinoma who underwent curative D2 gastrectomy between October 1995 and September 2005 were reviewed. RESULTS: A total of 22 patients (23%) had positive PWC. Factors significantly associated with positive PWC included tumor location, macroscopic findings, histology, depth of tumor invasion, nodal involvement, TNM stage, and angiolymphatic invasion. Positive PWC was found only in tumors invading the serosa. All patients with positive PWC developed peritoneal recurrence. The sensitivity and specificity of positive PWC in predicting peritoneal recurrence were 61% and 100%, respectively. The overall 5-year survival rates for patients with positive and negative PWC were 0% and 75%, respectively. CONCLUSION: Gastric adenocarcinoma with positive PWC should be considered stage IV disease. PWC should be included in the staging of gastric adenocarcinoma. PMID- 17334714 TI - Distribution of free cancer cells in the abdominal cavity suggests limitations of bursectomy as an essential component of radical surgery for gastric carcinoma. AB - BACKGROUND: Bursectomy, which has been performed so as to resect peritoneal deposits disseminated within the omental bursa, is considered as an essential component of radical surgery for gastric carcinoma in Japan. Bursectomy has also been described in the Japanese Treatment Guidelines for Gastric Carcinoma as a mandatory procedure for the treatment of serosa-positive cancer. However, no evidence to support the prognostic significance of this procedure has been reported to date. METHODS: Cytologic examination and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of the peritoneal washes obtained from the Douglas pouch, left subphrenic cavity, and inside the omental bursa were performed for 136 patients who underwent potentially curative surgery for gastric carcinoma. RESULTS: Carcinoembryonic antigen (CEA) or cytokeratin (CK) 20 mRNA was detected in one or more samples from the three different sites of peritoneal washes in 43 of the 136 patients. In 14 patients, the mRNAs were detected in samples obtained from the bursa omentalis (10.3% of all patients and 32.6% of patients with positive RT-PCR results). In 12 of these 14 patients, the mRNAs were also detected in samples taken from either or both of the remaining two sites. Only in the 2 other patients was the sample only from inside the omental bursa positive for CEA. CONCLUSION: It is unlikely that viable cancer cells disseminated into the bursa remain restricted to this cavity without migrating into the free abdominal cavity. Routine bursectomy may not be an essential procedure for resecting gastric cancer, from the viewpoint of eliminating microscopic peritoneal deposits within the omental bursa. PMID- 17334715 TI - Role of staging laparoscopy with peritoneal lavage cytology in the treatment of locally advanced gastric cancer. AB - BACKGROUND: More accurate preoperative staging is necessary to determine the treatment strategy for locally advanced gastric cancer. Laparoscopy has been suggested as an appropriate staging modality. The aim of this study was to clarify the role of staging laparoscopy in patients with locally advanced gastric cancer. METHODS: One hundred patients with primary gastric adenocarcinoma underwent laparoscopy with peritoneal lavage cytology. The disease stages determined were compared with those obtained by conventional methods. RESULTS: The disease stages were corrected after laparoscopy for 47 of the 100 patients (47%), with downstaging in 3 (3.0%) and upstaging in 44 (44%). Peritoneal deposits were found in 7 patients with peritoneal dissemination diagnosed by conventional examination. An unsuspected peritoneal deposit was found in 21 of 93 patients (22.6%), and unsuspected free cancer cells without deposits were found in 27 of 93 patients (29.0%). Gastrectomy after staging laparoscopy was performed in 39 patients. Laparoscopy showed no peritoneal deposits in any of these patients. Free cancer cells were found in 9 patients (23.1%), but 4 of these had peritoneal deposits at operation. R0 resection was performed in 34 of the 39 patients (87.2%). Neoadjuvant chemotherapy after staging laparoscopy was performed in 35 patients. All 35 patients underwent gastrectomy, which resulted in 27 R0 and 8 R2 resections. Of 18 patients with positive cytology at laparoscopy, 11 had no free cancer cells at operation. Neoadjuvant chemotherapy induced downstaging of the disease in 11 of the 18 patients with positive cytology (61.1%). Of 26 patients with massive peritoneal deposits, 4 underwent palliative resection because of pyloric stenosis. Twenty-two patients (22.0%) were able to avoid unnecessary laparotomy because of the staging laparoscopy. CONCLUSION: Staging laparoscopy with peritoneal lavage cytology is a safe, effective tool in patients with locally advanced gastric cancer, especially in patients receiving neoadjuvant chemotherapy. PMID- 17334716 TI - Indications for EMR/ESD in cases of early gastric cancer: relationship between histological type, depth of wall invasion, and lymph node metastasis. AB - BACKGROUND: Limited surgery by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for gastric cancer is frequently performed in many institutions. These techniques do preserve gastric function and maintain a high quality of life but may compromise survival. The treatment strategy for early tumors should therefore be based on a complete cure, and limited surgery must thus have clear indications. METHODS: D2 gastric resection was performed in 278 early gastric adenocarcinomas, and a retrospective histological review of the specimens was made. The extended indications for EMR or ESD, according to the Japanese Gastric Cancer Association Treatment guidelines for gastric cancer in Japan, were also assessed. RESULTS: Of the 278 early gastric cancers, 115 were mucosal (M) cancers without ulcer. No lymph node metastases were seen in these specimens. Six of the 41 specimens of M cancer with ulcers had lymph node metastases at the N1 level only. One of these had lymph node metastases from a tumor measuring less than 3 cm in size. Twenty-eight of 122 submucosal cancers had lymph node metastases (23%). Twenty of these were SM1 tumors and 5 had lymph node metastases; 4 of these 5 had lymph node metastases despite the absence of vascular invasion. CONCLUSION: Three cases had lymph node metastases that met the extended criteria for EMR/ESD. EMR and/or ESD should be limited to M cancers without ulcer or differentiated-type M cancer with ulcers smaller than 2 cm. When the depth of tumor invasion is deeper than M, then a gastric resection with lymph node dissection is necessary. PMID- 17334717 TI - Impact of age on postoperative outcomes in 1118 gastric cancer patients undergoing surgical treatment. AB - BACKGROUND: The purpose of the study was to evaluate the impact of age on outcomes in gastric cancer surgery. METHODS: Patients on the hospital database who underwent gastric resection for gastric cancer during the period 1990-2005 (n = 1118) were divided into two groups: group A, patients 75 years or older (n = 249), and group B, those younger than 75 years (n = 869). RESULTS: Overall preoperative complications were diagnosed in 92 (37%) patients of group A, compared with 147 (17%) in group B (P = 0.002). Fifty-five percent of patients underwent resection with D2 or more lymph node dissection (37% [n = 93] in group A, and 60% [n = 521] in group B; P = 0.003). Postoperative overall morbidity was higher in the elderly group (29% in group A versus 23% in group B), but the difference between the two groups was not significant (P = NS). Overall postoperative surgical complications were recorded in 201 (18%) patients; 49 (20%) in the elderly cohort, compared with 147 (17%) in the younger group (P = NS). The postoperative mortality rate was 3% (n = 7) in the elderly group, compared with 3% (n = 26) in the younger cohort (P = NS). Multivariate Cox analysis showed that age was not an independent risk factor for postoperative morbidity and mortality. Overall 5-year survival was 47% in group A and 54% in group B (P = NS). CONCLUSION: Due to improved perioperative management, resection of gastric carcinoma is the treatment of choice in elderly patients. Although comorbidities were more frequent among the elderly patients, postoperative morbidity and mortality, even after extensive resections, was low. Survival rates were comparable to those in the younger patients. PMID- 17334718 TI - Expression of phosphorylated Akt (pAkt) in gastric carcinoma predicts prognosis and efficacy of chemotherapy. AB - BACKGROUND: The Akt signaling pathway controls the survival and growth of human cancers. We investigated the expression of phosphorylated Akt (pAkt) in patients with gastric cancer. METHODS: The expression of pAkt was immunohistochemically examined in 140 gastric cancer patients who underwent a gastrectomy. The expression of pAkt was evaluated based on staining intensity, and staining was classified as negative or positive. We examined the expression of pAkt and its association with the clinicopathological findings, prognosis, depth of invasion, the expression of p53, and efficacy of oral fluorouracil chemotherapy after surgery. RESULTS: Expression of pAkt was positive in 81 (58%) patients and negative in 59 (42%) patients. There were no significant correlations between pAkt expression and the clinicopathological findings. The prognosis of patients with pAkt-negative tumors was superior to that of patients with pAkt-positive tumors, and the difference was significant for T3/T4 gastric cancer (P < 0.05). Among the patients with T3/T4 gastric cancer, postoperative oral fluorouracil treatment was effective in those who were pAkt-positive. Multivariate analysis revealed that pAkt expression and lymph node metastasis were independent prognostic factors. In 88 patients with T3 gastric carcinoma who had undergone curative surgery, in whom we studied the prognostic impact of a combined analysis of pAkt and p53 expression, patients with both pAkt- and p53-positive tumors showed a significantly poorer prognosis than patients with either or both pAkt- and p53-negative tumors (P < 0.05). CONCLUSION: Our results indicate that pAkt expression may be useful for predicting the prognosis and efficacy of fluorouracil treatment in patients with gastric cancer. PMID- 17334719 TI - Pharmacokinetic study of weekly administration dose of paclitaxel in patients with advanced or recurrent gastric cancer in Japan. AB - BACKGROUND: We aimed to clarify the relationship between the maximum tolerated dose and plasma concentration of paclitaxel in Japanese patients with gastric cancer on a weekly paclitaxel administration regimen. METHODS: Thirty-three patients with advanced or recurrent gastric cancer were treated with escalating doses of paclitaxel, administered weekly, along with a fixed dose of 5 fluorouracil or cisplatin. RESULTS: The plasma concentration of paclitaxel remained above 8.5 ng/ml for 24 h after administration. The mean area under the curve increased significantly with escalating dosage levels (R = 0.63; P 0.001). At level 4, patients showing dose-limiting toxicity had a significantly higher plasma paclitaxel concentration than patients without it. CONCLUSION: The weekly administration of paclitaxel, for which a single dose is about one-third of the dose for a tri-weekly treatment regimen, is clinically feasible and appropriate in terms of toxicity and the maintenance of an effective plasma concentration. PMID- 17334720 TI - Successful treatment of advanced gastric cancer by surgical resection following combination chemotherapy with oral S-1 and biweekly paclitaxel. AB - We report on the successful treatment of advanced gastric cancer by surgical resection following neoadjuvant chemotherapy. A 67-year-old man was referred to our hospital with a diagnosis of pancreatic cancer. Meticulous examination, however, revealed the presence of gastric cancer with ascites and large lymph node metastasis adjacent to the pancreas. We selected combination chemotherapy with oral S-1 and biweekly paclitaxel. After two courses, both the primary tumor and metastatic lymph nodes were greatly reduced, and the ascites had disappeared. Using laparoscopy, there was no evidence of peritoneal metastases, and the cytological examination was negative. The patient underwent distal gastrectomy with D2 lymph node dissection. Histological examination revealed that the cancer cells were still present in part, but no lymph node metastases were found. The tumor was pathologically diagnosed as pT2, pN0, P0, M0, CY0, and p-stage II. The patient is healthy over 4 years after surgery without recurrence. PMID- 17334721 TI - Gastric carcinosarcoma presenting as a huge epigastric mass. AB - Gastric carcinosarcoma often presents with an elevated lesion or increased thickness of the stomach wall. Histological diagnosis is achieved using conventional hematoxylin and eosin staining to confirm the coexistence of both epithelial and mesenchymal elements. We report a case of gastric carcinosarcoma presenting as a large mass in the epigastric region. Specimens obtained by endoscopic biopsy and surgical excision showed diffuse proliferation of atypical cells in sheet formation. No mucus production or glandular structures were apparent, but immunoreactivity for both epithelial and mesenchymal markers was noted. These findings led to a definitive diagnosis of gastric carcinosarcoma. Immunohistochemical analysis is useful for the early diagnosis and treatment of gastric carcinosarcoma. PMID- 17334722 TI - Pneumocystis pneumonia in patients with HIV infection: clinical manifestations, laboratory findings, and radiological features. AB - Pneumocystis pneumonia (PCP) remains the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). Familiarity with the clinical features of PCP is crucial for prompt diagnosis, even if the patient is unaware of their HIV serostatus. We describe herein the clinical features of 34 episodes in 32 patients with AIDS-associated PCP and review the existing literature. As for symptoms, the frequency of fever, cough, and dyspnea was 74%, 74%, and 65%, respectively, and the complete triad was present in only 14 of the 34 episodes on first examination. Median duration from onset of symptoms until diagnosis was 3 weeks, and AIDS-associated PCP tended to take an insidious clinical course. Although laboratory findings were generally nonspecific, measurement of beta-D-glucan levels in the serum or plasma was highly useful in the diagnosis of PCP. All but 1 of the patients showed beta-D-glucan levels higher than the cutoff value (median, 147 pg/ml; range, 5-6920 pg/ml). Typical radiographic features of PCP are bilateral, symmetrical ground-glass opacities, but a wide variety of radiographic findings were observed. In our patients, high resolution computed tomography (HRCT) of the lung showed ground-glass opacities sparing the lung periphery (41% of episodes) or displaying a mosaic pattern (29%), or being nearly homogeneous (24%), ground-glass opacities associated with air-space consolidation (21%), associated with cystic formation (21%), associated with linear-reticular opacities (18%), patchily and irregularly distributed (15%), associated with solitary or multiple nodules (9%), and associated with parenchymal cavity lesions (6%). PMID- 17334723 TI - Radiological findings of mycobacterial diseases. AB - The diagnosis and treatment of mycobacterial diseases are very important clinical issues. Among mycobacterial diseases, pulmonary tuberculosis remains an important cause of morbidity and mortality throughout the world. Pulmonary tuberculosis demonstrates a variety of clinical and radiological features. In addition, the prevalence of Mycobacterium avium complex (MAC) has increased, especially in elderly women without underlying diseases. Clinically, there is a significant difference between tuberculosis and atypical mycobacterium infection in terms of the infection control measures adopted and the choice of treatment. Therefore, it is very important to know the characteristic radiological findings of mycobacterial diseases. In the present review, key radiological points for diagnosing mycobacterial diseases are discussed. PMID- 17334724 TI - Resistance to gram-negative organisms due to high-level expression of plasmid encoded ampC beta-lactamase blaCMY-4 promoted by insertion sequence ISEcp1. AB - A Klebsiella pneumoniae strain, KU6500, which showed resistance to extended spectrum beta-lactams and produced the plasmid-encoded AmpC beta-lactamase CMY-4, was identified from clinical isolates in Japan. The aim of this study was to identify the mechanism of the high-level expression of blaCMY-4. Sequence analysis indicated that the promoter element of Citrobacter freundii was conserved, but the insertion sequence ISEcp1 coding with the putative promoter element, was inserted into the AmpR binding site. We determined the influence of the promoter on blaCMY-4 expression and beta-lactam resistance. Two recombinant plasmids containing the entire blaCMY-4 gene, with or without the ISEcp1-mediated promoter sequences, were constructed and named pMWampC and pMWISEcp1, respectively. Escherichia coli DH5alpha (pMWISEcp1) was resistant to almost all beta-lactams tested and E. coli DH5alpha (pMWampC) was susceptible to all, except for cephalothin. In addition, the activity of each promoter was measured by subcloning the element into a promoterless luciferase plasmid pGL3-Basic vector. The expression of the putative promoter of ISEcp1 was 18.9-fold higher than that of C. freundii. These results suggest that the putative promoter element of ISEcp1 is necessary for the high-level expression of blaCMY-4 to confer resistance to extended-spectrum cephalosporins. PMID- 17334725 TI - Differences in antimicrobial susceptibility breakpoints for Pseudomonas aeruginosa, isolated from blood cultures, set by the Clinical and Laboratory Standards Institute (CLSI) and the Japanese Society of Chemotherapy. AB - A study was made of the antimicrobial susceptibility to and efficacy of various kinds of antimicrobial agents against 179 strains of Pseudomonas aeruginosa that were isolated from blood cultures at Kansai Medical University Hospital from 1990 through 2004. The annual detection rate was highest in 1994, at 22 strains (6.5%). There were 9 multidrug resistant strains of Pseudomonas aeruginosa (5.0%). Among 14 antimicrobial agents tested for measurements, ciprofloxacin (CPFX) showed the best minimum inhibitory concentration (MIC) 50 value, of 0.25 microg/ml, followed by pazufloxacin (PZFX) and biapenem (BIPM), each at 0.5 microg/ml. When the period of 15 years was divided into three stages, the MIC50 value for each antimicrobial agent was highest in the middle stage (1995 to 1999). Assuming that the percentage of sensitive strains according to the breakpoints set by the Clinical and Laboratory Standards Institute (CLSI) represents the antimicrobial susceptibility rate, amikacin (AMK) showed the best value, of 85.5%. According to the sepsis breakpoint set by the Japanese Society of Chemotherapy (JSC), the efficacy of CPFX showed the highest rate (77.1%) of all the antimicrobial agents tested. Among beta-lactams, BIPM showed the highest efficacy rate, of 67.0%. When the efficacy rates were compared with each other, the difference in efficacy rate between the breakpoint set by the CLSI and the sepsis breakpoint set by the JSC was large for beta-lactams. Comparisons made based on the CLSI criteria showed no difference in cross-resistance rates between CPFX, meropenem (MEPM), and BIPM. However, when comparisons were made using the JSC sepsis breakpoint, MEPM showed a cross-resistance rate of 87.8%, while the rate for BIPM was lower, at 56.1%, with the chi2 test showing a significant difference, at P = 0.0014. In accordance with the pharmacokinetics/pharmacodynamics theory that has been advocated, breakpoints which are more suitable for the clinical setting in Japan should be set so that more effective and more appropriate treatment can be carried out. PMID- 17334726 TI - Invasive Haemophilus influenzae infections in children in Kamikawa subprefecture, Hokkaido, Japan, 1996-2005, before the introduction of H. influenzae type b vaccination. AB - We evaluated 52 children with invasive Haemophilus influenzae infection in Kamikawa subprefucture, Hokkaido, Japan between 1996 and 2005. The most frequent disease was meningitis, in 30 children (57.7%), followed by pneumonia in 9 (17.3%), bacteremia in 8 (15.4%), epiglottitis in 4 (7.7%), and cellulitis in 1 (1.9%). Patients ranged in age from 0 days to 8 years. Thirty (57.7%) of the patients were less than 2 years old. Only 6 cases of invasive H. influenzae infection occurred in children older than 5 years. Between 1996 and 2005 the annual incidence rates of invasive H. influenzae infection in children aged less than 5 years, and those aged from 5 to 9 years were 4.3/100,000 to 56.8/100,000 and 0/100,000 to 12.4/100,000, respectively. A marked increase of the annual incidence rate in children aged under 5 years was observed in the most recent 2 years (2004 and 2005). No patients with invasive H. influenzae infection died, but sequelae were seen at discharge in 2 patients with meningitis, predominantly epilepsy and developmental delay of varying severity. Two patients with epiglottitis were treated by endotracheal intubation or tracheostomy. Of 41 strains isolated from 1999 to 2005, 35 were classified for antimicrobial resistance by the polymerase chain reaction (PCR) method. The number of strains of beta-lactamase-negative ampicillin-susceptible, low beta-lactamase-negative ampicillin-resistant, beta-lactamase-negative ampicillin-resistant, beta lactamase-negative amoxicillin/clavulanic acid resistant-I, and beta-lactamase positive amoxicillin/clavulanic acid resistant-II, were 22, 3, 5, 2, and 3, respectively. The serotype in 37 (97.4%) of 38 cases demonstrated type b. PMID- 17334727 TI - Prevalence of toxin A-nonproducing/toxin-B-producing Clostridium difficile in the Tsukuba-Tsuchiura district, Japan. AB - In Japan, many clinical laboratories may not have recognized toxin A nonproducing/toxin B-producing (A-/B+) Clostridium difficile, because rapid diagnostic kits detecting toxin B of C. difficile have not been available in the laboratories. Therefore, we examined the prevalence of A-/B+ strains in the Tsukuba-Tsuchiura district, Japan. Fecal specimens submitted for C. difficile toxin tests in four tertiary hospitals in the district were collected for 6 months. Several C. difficile A-/B+ strains, isolated in two nosocomial outbreaks that had occurred in geographically distant areas in Japan, were also simultaneously analyzed as controls. C. difficile was isolated from 159 of 332 specimens collected. Ten (6.3%) of the 159 C. difficile strains were A-/B+ strains. Nine A-/B+ strains, isolated in one hospital, had an identical genomic pattern by polymerase chain reaction (PCR) ribotyping and macrorestriction analysis with pulsed-field gel electrophoresis (PFGE). The A-/B+ strain isolated in another hospital and some of those in the geographically distant hospitals were indistinguishable from the nine strains by PCR ribotyping but were distinguishable with PFGE analysis. We concluded that A-/B+ strains are not epidemic in this district and that PFGE analysis may be preferable to PCR ribotyping for the genotyping of C. difficile A-/B+ strains. The reason why most of the A-/B+ strains were detected in the one hospital was unclear. PMID- 17334728 TI - Plasma concentration of micafungin in patients with hematologic malignancies. AB - In 20 patients with hematologic malignancies, we measured the plasma concentration of micafungin (MCFG) by high-performance liquid chromatography after drip infusion of MCFG, at 150 mg/day over a 1-h period, and we analyzed the results in relation to the patients' laboratory parameters of liver and kidney function. Measurement of the plasma concentration was performed at the end of the initial administration of MCFG, 5 to 6 h after the start of the initial administration, immediately before the second dosing, immediately before the fourth dosing, and at the end of the fourth dosing. The plasma concentration of MCFG was correlated with the doses of MCFG per kilogram body weight (P = 0.0008 0.0036). The peak after the initial administration was 2.6 times higher than the trough value after the initial administration. The steady-state trough value was 1.2 times higher than the trough value after the initial administration. There was no correlation between the liver/kidney function parameters and the plasma concentration of MCFG. These results suggest that there was a good correlation between the plasma concentration of MCFG and the dose of MCFG per kilogram body weight, and that MCFG can be administered safely to patients with liver or kidney dysfunction without adjusting the dose. PMID- 17334729 TI - Rapidly progressive invasive pulmonary aspergillosis in a diabetic man. AB - A 45-year-old man was admitted to our hospital with high fever and a large amount of gray sputum. His initial chest X-ray showed broncho-bronchiolitis and thickening of the large bronchus, and he was subsequently diagnosed with pulmonary aspergillosis based on his sputum culture, polymerase chain reaction for Aspergillus fumigatus, and mannan antigen for Aspergillus. His immune responses, including neutrophil phagocytosis function and neutrophil sterilizing function, were normal as far as we could determine. He was treated with itraconazole, amphotericin B, and meropenem trihydrate, but died of respiratory failure on the twenty-fifth hospital day. Chest X-ray showed rapidly progressive invasive shadows in both lung fields, resulting in multiple cavity formation. This was a rare case of invasive pulmonary aspergillosis in a diabetic man with normal neutrophil phagocytosis function and neutrophil sterilizing function. PMID- 17334730 TI - HIV infection with concomitant cerebral toxoplasmosis and disseminated histoplasmosis in a 45-year-old man. AB - Although disseminated histoplasmosis is a common opportunistic infection in HIV patients in endemic areas, it is not widely known in Japan. We report a rare case of a man from Ghana infected with HIV who was hospitalized in Japan and who suffered from coinfection with cerebral toxoplasmosis and disseminated histoplasmosis. The diagnosis of cerebral toxoplasmosis was confirmed by a brain biopsy, and the therapy for the disease resulted in almost complete resolution of the brain lesion. However, fever of unknown origin continued for 2 weeks, and disseminated histoplasmosis was diagnosed by examination of a blood smear and by the detection of the histoplasma genome in the peripheral blood by means of polymerase chain reaction. The isolate was confirmed to be Histoplasma capsulatum var. duboisii. Therapy with amphotericin B was initiated, and no histoplasma genome in the peripheral blood was detected 3 days later. Unfortunately, the patient died after 10 days from acute respiratory syndrome. This case highlights that histoplasmosis should be included in the differential diagnosis of opportunistic infections in AIDS patients when patients have a history of travel to or arrival from endemic areas. PMID- 17334731 TI - Simple methodology for detecting time shifts in surgical site infections: a study in digestive, breast, and thoracic surgery. AB - To simplify the data mining surveillance system for the monitoring of surgical site infections (SSIs), electronic analysis of a total of 3100 patients was done. Using Layered Analyses, the Cross-Table option of a globally available software detected emerging or disappearing SSIs according to specific parameters. This methodology may facilitate the detection of SSI shifts. PMID- 17334732 TI - Procedures for prevention of perinatal group B streptococcal diseases: a multicenter questionnaire survey of hospitals in the Kyoto Neonatal Disease Study Group, Japan. AB - To explore clinical protocols for the prevention of early-onset group B Streptococcus (EOGBS) disease of the newborn in Japan, we conducted a multicenter questionnaire survey. Of 32 regional centers participating in the Kyoto Neonatal Study Group, 28 provided usable data concerning prevention practices undertaken between 2000 and 2004. Twenty-three (82%) of the 28 hospitals implemented bacteriological screening to identify maternal GBS carriage, and all 23 hospitals administered intrapartum antibiotics to all screening-positive pregnant women. There were no institutes that used risk-based strategies. In the 23 hospitals, bacteriological screening was conducted mostly by lower vaginal swab alone (n = 18). Eighteen hospitals performed screening once during pregnancy, either before 34 weeks' gestation (n = 6) or between 35 and 37 weeks' gestation (n = 12). Oral antepartum antibiotics, when carriage was identified, were administered at 12 (52%) hospitals. Twenty institutes used penicillins for intrapartum prophylaxis. However, the loading dose for chemoprophylaxis ranged from 0.5 to 2 g, and the interval between repeat administrations ranged from 4 to 12 h. Although the results indicated that more than 80% of the hospitals surveyed had introduced some screening-based prevention practices, the timing of the bacteriological screening during the pregnancy, the number of screenings, and the screening sites, as well as the antibiotics used, and their dosage, varied widely. Because of these highly variable methods, the efficacy of the implementation of preventive practices could not be determined. This study is the first to have described preventive practices for EOGBS disease in Japan in the era of Centers for Disease Control and Prevention guidelines. In light of the above results, a larger study under a unifying protocol would be warranted. PMID- 17334733 TI - Extensive multidrug resistance of coagulase-negative staphylococci in medical students. AB - Staphylococcus aureus and coagulase-negative staphylococci (CNS) isolated from the nasal mucosa of medical students were examined for susceptibility to 16 antimicrobial agents. No methicillin-resistant S. aureus (MRSA) was isolated, while MRCNS was present in 23.5% of the medical students. CNS exhibited significantly more resistance to antimicrobial agents such as gentamicin, in addition to oxacillin, compared to S. aureus, and 13.1% of the CNS strains (mostly MRCNS) were multidrug-resistant (to five or more drugs). In contrast, ampicillin resistance was higher in S. aureus. The rate of hospitalization or of taking an antimicrobial agent within the past 1 year was lower in CNS+ students than in S. aureus+ students. The data suggest that CNS could serve as a reservoir of drug resistance by persistent colonization in the nasal mucosa. In this study, MRCNS with multidrug resistance was found in medical students. More attention should be given to nasal MRCNS in medical students as a possible spreader in hospitals. PMID- 17334734 TI - [Basic treatment of early rheumatoid arthritis. Abstaining from rheumatological care and preferring alternative medicine increase the risk of undertreatment]. AB - The major challenge in the management of rheumatoid arthritis (RA) is the early initiation and long-term continuation of disease-modifying antirheumatic drug (DMARD) therapy. A total of 916 RA patients (ACR criteria, disease duration <2 years) were investigated in regard to frequency and reasons for DMARD discontinuation. All patients were under rheumatological care at the start of the observation and almost all were receiving DMARDs at study entry (95%). The proportion decreased to 87% within 3 years. Of the 171 patients without DMARD, 5% abstained due to (planned) pregnancy, 28% due to contraindications and/or severe adverse events and 54% due to remission. Only 12% were non-compliant. Multivariate regression analysis revealed non-specialised care (OR 4.6; 59% CI 3.2-6.7), RF seronegativity (OR 2.6; 95% CI 1.8-3.8), no patient education (OR 2.2; CI 95% 1.5-3.4), preference for alternative medicine (OR 8.2; 95% CI 4.0 16.8) and > or =10 years of education (OR 1.8; 95% CI 1.3-2.7) as independent risks for DMARD abstention. Age, sex, comorbidity or disease activity did not influence adherence to DMARD therapy. Since preference for alternative medicine was the strongest risk predictor, further investigations are needed to determine the characteristics of this preference regarding compliance with DMARD medication in RA. The positive influence of patient education on DMARD continuation emphasizes its importance. PMID- 17334735 TI - [COX-2 inhibitors and cardiovascular events]. PMID- 17334736 TI - [Glucocorticoid induced osteoporosis]. AB - Secondary osteoporosis is caused by various non-physiological factors. It affects 5% of all patients with osteoporosis and accounts for 20% of all osteoporotic fractures. Glucocorticoid induced osteoporosis is the most common form of secondary osteoporosis, whereas an endogenous Cushing syndrome rarely results in decreased bone mineral density. In addition, chronic inflammatory diseases which require a glucocorticoid therapy also need to be considered in the context of osteoporosis. This article presents the current data on glucocorticoid induced osteoporosis and an update of the proposed DVO (Dachverbandes Osteologie, umbrella organization of German scientific osteology-related societies) guidelines 2006. PMID- 17334737 TI - Sub-Saharan Africa descendents in Rio de Janeiro (Brazil): population and mutational data for 12 Y-STR loci. AB - A male sample of 135 African descendents from the Rio de Janeiro population were typed for the 12 Y-chromosome short tandem repeat (STR) loci included in the PowerPlex Y System. A high haplotype diversity was observed (0.9971), with 91% of haplotypes being unique, demonstrating the usefulness and informative power of this Y-STR set in male lineage identification. Samples with shared haplotypes were additionally typed with the Yfiler kit, which includes five extra markers. The haplotype diversity when using the 17-Yfiler loci increased to (0.9998) with 97% unique haplotypes. The same set of Y-STRs was also typed in 135 father/son pairs and three single-step mutations were observed: one at DYS19 and two at DYS385. Genetic distance analysis showed highly significant differences in all pairwise comparisons between this sample of African descendents and the general population from Rio de Janeiro, as well as with Iberian and African samples from Portugal, Mozambique, Angola and Equatorial Guinea. Comparisons with samples from other regions in Brazil showed that heterogeneity does exist, indicating that a Y haplotype database for the whole country should take into account the population sub-structure. Moreover, a strong European influence was detected, and thus, a Y chromosome STR profile proves a rather poor indicator for the ethnic origin of an individual in Rio de Janeiro. PMID- 17334738 TI - ? PMID- 17334739 TI - [None fly over the cuckoo's nest anymore. Electroconvulsive therapy and anesthesia]. PMID- 17334740 TI - [Out-of-hospital airway management in northern Germany. Physician-specific knowledge, procedures and equipment]. AB - BACKGROUND: Out-of-hospital airway management confronts emergency medical teams with complex challenges. To date no specific data are available on the qualifications of emergency physicians (EPs) and the quality of emergency equipment in northern Germany. MATERIALS AND METHODS: This study surveyed individual EPs at regional emergency dispatch centres about their personal knowledge and skills, and the procedures and equipment used in out-of-hospital airway management. RESULTS: A total of 606 EPs from 59 of the 66 (89.4%) regional emergency dispatch centres surveyed responded and 56.1% of the EPs questioned were anesthesiologists. The other EPs were qualified in either internal medicine (22.6%), surgery (12.4%), general medicine (5.6%) or other specialties (3.3%). All (100%) of the EPs trained in anesthesia and 35.2% of the other EPs reported that they had performed more than 100 in-hospital endotracheal intubations (ETI). 93% of all EPs rated out-of-hospital ETI as more difficult than in-hospital ETI. A total of 33.0% of anesthesia-trained EPs and 6.1% of the other EPs used muscle relaxants for ETI in more than 20% of the cases. Of the anesthesia-trained EPs 38.1% used expiratory CO(2) monitoring to verify tube placement compared to 12.1% of the other EPs. A total of 97.8% of anesthesia-trained EPs reported having used an extra-glottic airway device more than 20 times compared to 11.1% of the other EPs. For the emergency equipment 44.4% included an extraglottic airway device, 57.8% a cricothyrotomy set and 27.1% CO(2) monitoring options. CONCLUSION: Neither the emergency equipment nor the physicians' knowledge and skills were sufficient to meet the special demands of out-of-hospital airway management, particularly among non-anesthesiologists. PMID- 17334741 TI - [Biomechanics of the arch of the foot. Pre- and postoperative radiological examination]. AB - The human foot is a complex biomechanical structure. The arch of the foot is formed by the bony and articular structure of the midfoot and supported by strong ligaments and tendons. The normal arch develops in childhood. Tendon and ligament rupture and degeneration often lead to flattening of the arch. Frequent painful conditions include hallux valgus deformity and rupture of the posterior tibial tendon both leading to flat feet. Radiological examination is necessary in a standardized, full weight bearing standing position. The standing dorsoplantar view shows hallux valgus angle and intermetatarsal 1/2 angle. The side view shows Lisfranc joint instability and decrease of the talometatarsal angle. Talonavicular instability is a frequent secondary sign of spring ligament and posterior tibial tendon lesion. After failure of conservative therapy, corrective surgery with osteotomy and realignment procedure of the malpositioned bones in combination with tendon and ligament reconstruction is the state of the art procedure. In postoperative follow-up a standing X-ray of the foot is again the standard tool. Additional MRI and CT examinations help to detect bone and cartilage lesions and tendon/ligament ruptures. PMID- 17334742 TI - [Serum-free cultivation of osteoprogenitor cells and osteoblasts to test biomaterials]. AB - The aim of the study is to describe a model for testing biocompatibility of implant materials. Usually cells do not bind the biomaterial surface itself via integrins but adsorbed proteins of blood or interstitial fluids. To eliminate the influence of serum proteins on cell adhesion to the test materials we cultivated osteoprogenitor cells and osteoblasts with a serum replacement or with fetal calf serum, but seeded them likewise without serum or serum replacement on cell culture polystyrene, sandblasted titanium and titanium coated with the peptide c(RGDfK) or hydroxyapatite (Bonemaster) and determined cell adhesion. In addition, the surfaces were preincubated with the serum proteins albumin, fetuin, fibronectin and vitronectin to examine specifically their influence on cell adhesion. Clearly cell adhesion depended on cell culture conditions and state of differentiation, especially with prominent differences in adhesion to c(RGDfK). Precoating with serum proteins demonstrated that besides fibronectin and vitronectin fetuin can function as an adhesion protein, whereas albumin demonstrated an antiadhesive effect. Depending on the material they affected cell adhesion differently. Although osteoprogenitor cells and osteoblasts could bind to tissue culture polystyrene, titanium and especially hydroxyapatite without mediation of proteins, it has to be taken into consideration that cell spreading and proliferation of cells on a scaffold are more important than adhesion alone and may not be ensured in the absence of adhesion proteins. PMID- 17334743 TI - [Therapy of retinal venous vascular occlusions]. PMID- 17334744 TI - [Depression of respiration via toxic effects on the central nervous system following use of topical brimonidine in an infant with congenital glaucoma]. AB - We report the case of a premature newborn (gestational age 33 weeks) with congenital glaucoma. After a trabeculotomy high intraocular pressure persisted, leading to adjuvant treatment with timolol and--when the infant was 3 weeks old- with brimonidine. After the first application of topical brimonidine the infant developed such severe apnoeic spells that intubation and temporary ventilation were necessary. A review of the literature reveals that when used in young infants brimonidine eye drops can potentially have toxic effects on the central nervous system (e.g. respiratory depression). The use of topical brimonidine is therefore not advised in this age group. PMID- 17334745 TI - [Intraocular application of bevacizumab for the treatment of choroidal neovascularization secondary to angioid streaks]. AB - Angioid streaks are the typical ophthalmological manifestation of the systemic disease pseudoxanthoma elasiticum. Fundoscopy reveals angioid streaks as irregular dark brownish lines radiating from the area around the optic disc. Choroidal neovascularization (CNV) is the major cause of severe visual loss in patients with angioid streaks. Argon-laser treatment of CNV secondary to angioid streaks shows poor results. Photodynamic therapy (PDT) with verteporfin does not seem to be an effective treatment for achieving stabilization of visual acuity and lesion size in CNV secondary to angioid streaks. Results after a combination of the intravitreal application of triamcinolone with PDT did not show the expected benefit. In the era of promising new intravitreal treatments for patients suffering from age-related macular degeneration, it is interesting to observe this effect of angiogenesis inhibitors (bevacizumab, ranibizumab, pegaptanib) in patients with neovascilarization secondary to angioid streaks. In our case, we observed a deterioration in visual acuity and leakage of the CNV after treatment with PDT alone. However, after the intravitreal injection of bevacizumab, we observed an improvement in vision, and the area of neovascularization changed into a fibrotic scar. A controlled study with long term results is needed to definitively evaluate this kind of treatment. PMID- 17334746 TI - [Therapy of temporomandibular joint pain: recommendations for clinical management]. AB - Arthralgias of the temporomandibular joint occur rarely in their isolated form, in contrast to myalgias of the jaw muscles. Most often, arthralgias are combined with myofascial pain. Here we define relevant terms (arthralgia, arthropathy, arthritis, osteoarthritis/osteoarthrosis), describe special diagnostic aspects and provide diagnosis-related specifications. We then present current information on the clinical management of temporomandibular joint pain. A systematic literature search revealed that pain reduction or pain relief can be achieved with non-invasive reversible methods for the majority of patients. Results from short and long-term longitudinal studies show that different therapeutic methods are similarly effective. For the management of chronic forms with extensive psychosocial impairment a multidisciplinary approach is essential. PMID- 17334747 TI - Antimicrobial therapy for Stenotrophomonas maltophilia infections. AB - Stenotrophomonas maltophilia has emerged as an important nosocomial pathogen capable of causing respiratory, bloodstream, and urinary infections. The treatment of nosocomial infections by S. maltophilia is difficult, as this pathogen shows high levels of intrinsic or acquired resistance to different antimicrobial agents, drastically reducing the antibiotic options available for treatment. Intrinsic resistance may be due to reduced outer membrane permeability or to the multidrug efflux pumps. However, specific mechanisms of resistance such as aminoglycoside-modifying enzymes or the heterogeneous production of metallo beta-lactamase have contributed to the multidrug-resistant phenotype displayed by this pathogen. Moreover, the lack of standardized susceptibility tests and their interpretative criteria hinder the choice of an adequate antibiotic treatment. Recommendations for the treatment of infections by S. maltophilia are based on in vitro studies, certain nonrandomized clinical trials, and anecdotal experience. Trimethoprim-sulfamethoxazole remains the drug of choice, although in vitro studies indicate that ticarcillin-clavulanic acid, minocycline, some of the new fluoroquinolones, and tigecycline may be useful agents. This review describes the main resistance mechanisms, the in vitro susceptibility profile, and treatment options for S. maltophilia infections. PMID- 17334748 TI - Elevated serum levels of visfatin in gestational diabetes: a comparative study across various degrees of glucose tolerance. AB - AIMS/HYPOTHESIS: Concentrations of visfatin are increased in insulin-resistant conditions, but the relationship between visfatin and insulin and/or insulin resistance indices in pregnancy remains unclear. Insulin resistance in pregnancy is further accentuated in women with gestational diabetes mellitus (GDM). Thus we assessed serum levels of visfatin in pregnant women with varying degrees of glucose tolerance. MATERIALS AND METHODS: Fasting visfatin levels were measured at 28 weeks of gestation in 51 women divided according to their response to a 50 g glucose challenge test (GCT) and a 75-g OGTT: control subjects (n = 20) had normal responses to both a GCT and an OGTT; the intermediate group (IG; n = 15) had a false-positive GCT, but a normal OGTT; the GDM group (n = 16) had abnormal GCTs and OGTTs. RESULTS: There were no age or BMI differences between analysed groups. Across the subgroups there was a progressive increase in glucose and insulin at 120 min of the OGTT (p < 0.01). This was accompanied by an increase in visfatin, from 76.8 +/- 14.1 ng/ml in the control subjects, to 84.0 +/- 14.7 ng/ml in the IG group and 93.1 +/- 12.3 ng/ml in the GDM group (p < 0.01 for GDM vs control subjects). There was a positive correlation between visfatin and fasting insulin (r = 0.38, p = 0.007) and insulin at 120 min of the OGTT (r = 0.39, p = 0.006). CONCLUSIONS/INTERPRETATION: An increase in fasting visfatin, the levels of which correlate with both fasting and post-glucose-load insulin concentrations, accompanies worsening glucose tolerance in the third trimester of pregnancy. However, the significance of these findings, and in particular the role of visfatin in the regulation of insulin sensitivity during pregnancy, remains to be elucidated. PMID- 17334749 TI - Prospective prediction of spontaneous but not recurrent autoimmune diabetes in the non-obese diabetic mouse. AB - AIMS/HYPOTHESIS: Type 1 diabetes is a T cell-mediated autoimmune disease with a clinically silent prodrome, during which prediction and treatment of disease are theoretically possible. Using retrospective analysis, spontaneous disease in the non-obese diabetic (NOD) mouse has been correlated with islet-specific glucose-6 phosphatase catalytic subunit-related protein (IGRP)-reactive CD8+ T cells in the peripheral blood. In this study, we determined prospectively whether IGRP reactive T cells in peripheral blood could predict disease occurrence. Since recurrent autoimmunity is an important contributor to transplant failure, we also determined whether failure of islet grafts (syngeneic and allogeneic) could be predicted by the presence of circulating autoreactive T cells. MATERIALS AND METHODS: Peripheral blood samples were taken weekly from female NOD mice between the ages of 8 and 30 weeks and from NOD mice transplanted with NODscid islets. Peripheral blood cells and islet grafts were analysed for the presence of IGRP reactive CD8+ T cells by flow cytometry. RESULTS: Prospective analysis of peripheral blood IGRP-reactive T cells in the prediabetic period predicted disease development with a sensitivity of 100% and a specificity of 60%, resulting in positive and negative predictive values of 85 and 100%, respectively. Significant proportions of IGRP-reactive T cells were found in the grafts, but not in peripheral blood of NOD mice undergoing syngeneic and allogeneic rejection. CONCLUSIONS/INTERPRETATION: The occurrence of spontaneous diabetes can be predicted prospectively by measuring peripheral blood autoreactive T cells. Rejection of syngeneic or allogeneic islets is associated with large populations of autoreactive CD8+ T cells within islets, suggesting that immunodominant autoreactive T cells during the prediabetic period are also responsible for autoimmune graft rejection. PMID- 17334750 TI - Finger interaction during maximal radial and ulnar deviation efforts: experimental data and linear neural network modeling. AB - The purpose of this study was to characterize finger interactions during radial/ulnar deviation, including interactions with flexion movements. Subjects performed single-finger and multi-finger maximal voluntary contraction (MVC), and maximal forces and various indices of interaction among the fingers were quantified. MVCs in radial/ulnar deviation were 50-80% as strong as in flexion. Along with the 'master' fingers (i.e., those explicitly instructed to produce force), substantial force production was also observed in 'slave' fingers (i.e., those not explicitly instructed to produce force), a phenomenon termed: force 'enslaving'. In addition, a drop in MVC during multi-finger tasks as compared to single finger tasks (force 'deficit') was also observed. A previously unreported phenomenon that we term: 'preferred direction enslaving' was also apparent; both master and slave fingers produced force in the instructed direction with a non zero perpendicular component. Due to the architectural separation of the involved muscles, preferred direction enslaving provides strong evidence that enslaving results from neural rather than biomechanical factors. A final new phenomenon: 'negative deficit', or force 'facilitation' was observed in 46.4% of the trials in 21 out of 23 subjects during multi-finger lateral efforts and was further demonstrative of extensive interconnection among neurons serving hand muscles. The data were modeled with high accuracy (approximately 4% mean square error) using a linear neural network with motor 'commands' as inputs and finger forces as outputs. The proposed network, equivalent to linear regression, can be used to determine the extent to which finger forces are influenced by peripheral constraints during functional prehensile activities. PMID- 17334751 TI - Use of fluroquinolone and risk of Achilles tendon rupture: a population-based cohort study. AB - OBJECTIVE: Several case-control studies have reported that the use of fluoroquinolone increases the risk of rupture of the Achilles tendon. Our aim was to estimate this risk by means of a population-based cohort approach. SETTING: Data on Achilles tendon ruptures and fluoroquinolone use were retrieved from three population-based databases that include information on residents of Funen County (population: 470,000) in primary and secondary care during the period 1991 1999. A study cohort of all 28,262 first-time users of fluoroquinolone and all incident cases of Achilles tendon ruptures were identified. MAIN OUTCOME MEASURES: The incidence rate of Achilles tendon ruptures among users and non users of fluoroquinolones and the standardised incidence rate ratio associating fluoroquinolon use with Achilles tendon rupture were the main outcome measures. RESULTS: Between 1991 and 2002 the incidence of Achilles tendon rupture increased from 22.1 to 32.6/100,000 person-years. Between 1991 and 1999 the incidence of fluoroquinolone users was 722/100,000 person-years, with no apparent trend over time. Within 90 days of their first use of fluoroquinolone, five individuals had a rupture of the Achilles tendon; the expected number was 1.6, yielding an age- and sex-standardised incidence ratio of 3.1 [(95% confidence interval (95%CI): 1.0-7.3). The 90-day cumulative incidence of Achilles tendon ruptures among fluoroquinolone users was 17.7/100,000 (95%CI: 5.7-41.3), which is an increase of 12.0/100,000 (95%CI: 0.0-35.6) compared to the background population. CONCLUSION: Fluoroquinolone use triples the risk of Achilles tendon rupture, but the incidence among users is low. PMID- 17334753 TI - Tempo and mode of evolution of the Rh blood group genes before and after gene duplication. AB - The Rh blood group genes became duplicated in a common ancestor of human chimpanzee-gorilla. We compared the evolutionary rates of the Rh blood group genes for each exon for branches connecting to humans, having duplicated Rh loci, and to orangutan, gibbon, and Old World monkeys, species having a single Rh locus. Our results show that evolutionary rates of nonsynonymous substitutions at exon 7 became accelerated in the human lineage. Furthermore, we surveyed the sequence variation in the region surrounding exon 7 of gibbons to clarify whether the diversity of the human exon 7 was introduced after the duplication or had been maintained before it. Two amino acid polymorphisms in white-handed gibbons were observed in the immediate vicinity of the D-specific motif in the human exon 7. Although the evolutionary rate of exon 7 was accelerated after the gene duplication, our results suggest that exon 7 had the potential for change even before the gene duplication. PMID- 17334752 TI - Decreased T2 signal in the thalami may be a sign of lysosomal storage disease. AB - INTRODUCTION: Lysosomal disorders are rare and are caused by genetically transmitted lysosomal enzyme deficiencies. A decreased T2 signal in the thalamus has occasionally been reported. AIMS: Because the finding of bilateral abnormal signal intensity of the thalamus on T2-weighted images has not been systematically reviewed, and its value as a diagnostic tool critically evaluated, we carried out a systematic review of the literature. METHODS: Articles in English with 30 trios of keywords were collected from PubMed. Exclusion criteria were lack of conventional T2-weighted images in the protocol and not being a human study. Finally, 111 articles were included. The thalamus was considered affected only if mentioned in the text or in the figure legends. RESULTS: Some 117 patients with various lysosomal diseases and five patients with ceruloplasmin deficiency were reported to have a bilateral decrease in T2 signal intensity. At least one article reported a bilateral decrease in signal intensity of the thalami on T2-weighted images in association with GM1 and GM2 gangliosidosis and with Krabbe's disease, aspartylglucosaminuria, mannosidosis, fucosidosis, and mucolipidosis IV. Furthermore, thalamic alteration was a consistent finding in several types of neuronal ceroid lipofuscinosis (NCL) including CLN1 (infantile NCL), CLN2 (classic late infantile NCL), CLN3 (juvenile NCL), CLN5 (Finnish variant late infantile NCL), and CLN7 (Turkish variant late infantile NCL). CONCLUSION: A decrease in T2 signal intensity in the thalami seems to be a sign of lysosomal disease. PMID- 17334754 TI - MHC class I A region diversity and polymorphism in macaque species. AB - The HLA-A locus represents a single copy gene that displays abundant allelic polymorphism in the human population, whereas, in contrast, a nonhuman primate species such as the rhesus macaque (Macaca mulatta) possesses multiple HLA-A-like (Mamu-A) genes, which parade varying degrees of polymorphism. The number and combination of transcribed Mamu-A genes present per chromosome display diversity in a population of Indian animals. At present, it is not clearly understood whether these different A region configurations are evolutionarily stable entities. To shed light on this issue, rhesus macaques from a Chinese population and a panel of cynomolgus monkeys (Macaca fascicularis) were screened for various A region-linked variations. Comparisons demonstrated that most A region configurations are old entities predating macaque speciation, whereas most allelic variation (>95%) is of more recent origin. The latter situation contrasts the observations of the major histocompatibility complex class II genes in rhesus and cynomolgus macaques, which share a high number of identical alleles (>30%) as defined by exon 2 sequencing. PMID- 17334755 TI - A novel-designed Escherichia coli for the production of various polyhydroxyalkanoates from inexpensive substrate mixture. AB - To efficiently produce polyhydroxyalkanoates (PHAs) from substrate mixture containing various carbon sources, Escherichia coli phosphotransferase system (PTS) mutants were constructed, in which the carbon catabolite repression in the presence of glucose was released. When cultivated in the medium containing glucose and xylose, E. coli LR1010, harboring phaC(Re) and phaAB(Re) genes from Ralstronia eutropha, could simultaneously consume glucose and xylose and accumulate short-chain-length PHA, whereas E. coli LR1120 and LR1110, harboring phaC1 gene from Pseudomonas aeruginosa, could accumulate medium-chain-length PHA. At the same time, LR1110 could simultaneously utilize the mixture of glucose and fatty acids. Semiquantitative reverse transcription polymerase chain reaction analysis indicated that disrupting phosphoenolpyruvate: sugar PTS in this strain released the repression on fad genes. PMID- 17334756 TI - Fetal calf serum-free culture of Chinese hamster ovary cells employing fish serum. AB - The effects of fish serum on cell growth and human granulocyte-macrophage colony stimulating factor (hGM-CSF) production in an adhesion culture of Chinese hamster ovary (CHO) cells DR1000L4N were investigated and compared with those of fetal calf serum (FCS). Although fish serum did not stimulate the initial adhesion of CHO cells to culture dishes, it prompted cell growth after cell adhesion with FCS for 24 h. The cell density in the fish serum medium reached 75% that in the FCS medium. Fish serum promoted cell adhesion to and cell growth on collagen-coated dishes. The cell-specific production rate of hGM-CSF in the fish serum medium on collagen-coated dishes was almost the same as that in the FCS medium. PMID- 17334757 TI - Microbial population in the biomass adhering to supporting material in a packed bed reactor degrading organic solid waste. AB - An anaerobic packed-bed reactor using carbon fiber textiles (CFT) as the supporting material was continuously operated using an artificial garbage slurry. 16S rRNA gene analysis showed that many bacteria in the biomass adhering to CFT were closely related to those observed from other anaerobic environments, although a wide variety of unidentified bacteria were also found. Dot blot hybridization results clarified that 16S rRNA levels of methanogens in the adhering biomass were higher than those in the effluent. Based on microscopic observation, the adhering biomass consisted of microorganisms, organic material, and void areas. Bacteria and Archaea detected by fluorescence in situ hybridization were distributed from the surface to the inner regions of the adhering biomass. Methanosarcina sp. tended to be more abundant in the inner part of the adhering biomass than at the surface. This is the first report to elucidate the structure of the microbial community on CFT in a packed-bed reactor. PMID- 17334758 TI - Purification and characterization of Vibrio parahaemolyticus extracellular chitinase and chitin oligosaccharide deacetylase involved in the production of heterodisaccharide from chitin. AB - A chitin-degrading bacterial strain, KN1699, isolated from Yatsu dry beach (Narashino, Chiba Prefecture, Japan), was identified as Vibrio parahaemolyticus. Treatment of powdered chitin with crude enzyme solution prepared from the supernatant of KN1699 cultures yielded a disaccharide, beta-D-N acetylglucosaminyl-(1,4)-D-glucosamine (GlcNAc-GlcN), as the primary chitin degradation product. The extracellular enzymes involved in the production of this heterodisaccharide, chitinase (Pa-Chi; molecular mass, 92 kDa) and chitin oligosaccharide deacetylase (Pa-COD; molecular mass, 46 kDa), were isolated from the crude enzyme solution, and their hydrolysis specificities were elucidated. These studies confirmed that (1) Pa-Chi hydrolyzes chitin to produce (GlcNAc)(2) and (2) Pa-COD hydrolyzes the acetamide group of reducing end GlcNAc residue of (GlcNAc)(2). These findings indicate that GlcNAc-GlcN is produced from chitin by the cooperative hydrolytic reactions of both Pa-Chi and Pa-COD. PMID- 17334759 TI - Intracellular expression of Vitreoscilla hemoglobin improves S-adenosylmethionine production in a recombinant Pichia pastoris. AB - To develop an efficient way to produce S-adenosylmethionine (SAM), methionine adenosyltransferase gene (mat) from Streptomyces spectabilis and Vitreoscilla hemoglobin gene (vgb) were coexpressed intracellularly in Pichia pastoris, both under control of methanol-inducible promoter. Expression of mat in P. pastoris resulted in about 27 times higher specific activity of methionine adenosyltransferase (SMAT) and about 19 times higher SAM production relative to their respective control, suggesting that overexpression of mat could be used as an efficient method for constructing SAM-accumulating strain. Under induction concentration of 0.8 and 2.4% methanol, coexpression of vgb improved, though to different extent, cell growth, SAM production, and respiratory rate. However, the effects of VHb on SAM content (specific yield of SAM production) and SMAT seemed to be methanol concentration-dependent. When cells were induced with 0.8% methanol, no significant effects of VHb expression on SAM content and specific SMAT could be detected. When the cells were induced with 2.4% methanol, vgb expression increased SAM content significantly and depressed SMAT remarkably. We suggested that under our experimental scheme, the presence of VHb might improve ATP synthesis rate and thus improve cell growth and SAM production in the recombinant P. pastoris. PMID- 17334760 TI - MR imaging of the posterolateral corner of the knee. AB - The posterolateral corner (PLC) is a complex functional unit, consisting of several structures, which is responsible for posterolateral stabilization. The PLC is not consistently defined in the literature. However, most descriptions include the popliteal tendon (PT), the lateral collateral ligament (LCL), the popliteofibular ligament (PFL) and the posterolateral capsule, which is reinforced by the arcuate ligament (AL) and the fabellofibular ligament (FFL). Knowledge of PLC anatomy, including its variations, and understanding of the biomechanics is important for correct diagnosis of PLC injuries. An overlooked PLC injury can result in chronic instability, chronic pain, and, eventually, in secondary osteoarthritis. Damage to the PLC also has an adverse effect on the outcome of cruciate ligament repair. Isolated lesions of the PLC are rare. PLC lesions are typically associated with injuries of the cruciate ligaments, the menisci, bone and soft tissue. In the acute phase, clinical findings can be difficult to interpret due to pain and swelling. Magnetic resonance (MR) imaging potentially demonstrates the entire spectrum of PLC injuries and associated lesions of the knee, including those that may be overlooked during clinical examination or arthroscopy. PMID- 17334761 TI - MR imaging of delamination tears of the rotator cuff tendons. AB - OBJECTIVE: The objective was to describe the imaging appearances and location of delamination tears of the rotator cuff tendons on non-contrast conventional MR imaging. SUBJECTS AND METHODS: This study was reviewed and approved by our Institutional Review Board. The reports of 548 consecutive MR examinations of the shoulder were reviewed, looking for mention or description of delamination tears of the rotator cuff. The images of the identified cases were then reviewed by two radiologists to confirm the findings. Correlation with surgical and arthroscopic information was then performed. Delamination tears were defined as horizontal retraction of either the bursal or articular surface of the tendon, manifest as thickening of the torn retracted edge, and/or interstitial splitting of the tendon, manifest as fluid-like high signal intensity on fat-suppressed T2 weighted oblique coronal images. RESULTS: Fourteen cases of delamination tears were identified in 13 patients. Ten of the cases involved the supraspinatus tendon, all with articular surface involvement. Nine of these supraspinatus cases were isolated tears and one occurred as part of a full thickness tear. All 10 of these supraspinatus cases showed medial retraction of the articular surface of the tendon, with thickening of the retracted edge, and 5 of the 10 had a demonstrable horizontal cleft in the interstitium. Four cases involved the subscapularis tendon, with articular surface disruption in three and pure interstitial delamination in one. Medial subluxation of the tendon of the long head of the biceps was present in all four cases. No delamination tears occurred on the bursal surface. Only three of the 14 shoulders underwent surgical repair with one confirmation of supraspinatus delamination, one confirmation of a subscapularis tear that had become a full thickness tear 10 months after initial imaging and another interstitial subscapularis delamination that was not identified arthroscopically. CONCLUSION: Delamination tears occur most often in the supraspinatus tendon, and in our series always involved the articular surface of the tendon. Only half of these tears have a visible cleavage plane in the interstitium, but this cleavage plane is not necessary for diagnosis if the torn edge is retracted. PMID- 17334762 TI - Assessment of intra- and interobserver reproducibility of rest and cold pressor test-stimulated myocardial blood flow with (13)N-ammonia and PET. AB - PURPOSE: We investigated the intraobserver reproducibility of myocardial blood flow (MBF) measurements with PET at rest and during cold pressor test (CPT), and the interobserver agreement. METHODS: Twenty normal volunteers were studied. Using (13)N-ammonia, MBF was measured at rest and during CPT and measurement was repeated in a 1-day session (short-term reproducibility; SR). After a follow-up of 2 weeks, MBF was measured again at rest and during CPT and compared with the initial baseline measurement (long-term reproducibility; LR). In addition, adenosine-induced hyperemic MBF increases were assessed. RESULTS: Assessment of the SR did not show a significant absolute difference in MBF at rest, MBF during CPT or the endothelium-related change in MBF from rest to CPT (DeltaMBF) (0.09 +/ 0.10, 0.11 +/- 0.09, and 0.08 +/- 0.05 ml/g/min; p = NS), and they were linearly correlated (r = 0.72, r = 0.76 and r = 0.84; p < 0.0001). Corresponding values for standard error of the estimate (SEE), as indicative for the range of MBF measurement error, were 0.14, 0.14, and 0.09 ml/g/min. The LR yielded relatively higher but non-significant absolute differences in the MBF at rest, MBF during CPT and DeltaMBF (0.10 +/- 0.10, 0.14 +/- 0.10, and 0.19 +/- 0.10 ml/g/min; p = NS), and paired MBFs significantly correlated (r = 0.75, r = 0.71, and r = 0.60; p < 0.001). Corresponding SEEs were 0.13, 0.15, and 0.16 ml/g/min. The interobserver analysis yielded a high correlation for MBF at rest, MBF during CPT, and hyperemic MBF (r = 0.96, SEE=0.04; r = 0.78, SEE=0.11; and r = 0.87, SEE=0.28; p < 0.0001, respectively), and also a good interobserver correlation for DeltaMBF (r = 0.62, SEE=0.09; p < 0.003). CONCLUSION: Short- and long-term MBF responses to CPT, as an index for endothelium-related coronary vasomotion, can be measured reproducibly with (13)N-ammonia PET. In addition, the high interobserver reproducibility for repeat analysis of MBF values suggests the measurements to be largely operator independent. PMID- 17334763 TI - Determination of tumour hypoxia with the PET tracer [18F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model. AB - PURPOSE: The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [18F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [18F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). METHODS: C3H mice were injected i.v. with an average of 12.95 MBq of [18F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. RESULTS: Ornidazole decreased the urinary excretion and increased the liver uptake of [18F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. CONCLUSION: Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation. PMID- 17334764 TI - Evaluation of 99mTc-UBI 29-41 scintigraphy for specific detection of experimental Staphylococcus aureus prosthetic joint infections. AB - PURPOSE: (99m)Tc-UBI 29-41 (UBI), an antimicrobial peptide, specifically targets bacteria. We tested the ability of UBI to discriminate between infected and uninfected prosthetic joints using a rabbit model previously validated. METHODS: Left knee arthroplasty was performed on 20 New Zealand rabbits, then 10(7) cfu of S. aureus (n = 12) or sterile saline (n = 8) was injected into the joint. On days 9 and 20 after surgery, planar UBI scintigraphy was performed in six infected and four uninfected rabbits, 1 h and 4 h p.i. (150 MBq), on a gamma camera. Operated to-normal knee activity ratio (ONKR) was calculated on each scintigram. Then, after sacrifice, tissue samples of both knees were counted in a gamma counter. RESULTS: One rabbit injected with sterile saline had cutaneous infection at sacrifice and was excluded from analysis. ONKR was higher in infected than in uninfected animals 4 h p.i. 20 days after surgery: 1.75 +/- 0.48 vs 1.13 +/- 0.11, p = 0.04. From 1 h to 4 h p.i., ONKR increased in 9/12 infected and 0/7 uninfected animals. According to UBI uptake intensity and kinetics, scintigraphy was truly positive in all infected cases on day 9 and in four of six infected cases on day 20. It was truly negative in two of three sterile inflamed prosthetic knees on day 9, and in all cases on day 20. Biodistribution studies revealed increased UBI uptake in periprosthetic tissues in all animals 9 days after surgery, and only in infected animals on day 20. CONCLUSION: In this experimental study, (99m)Tc-UBI 29-41 scintigraphy permitted the early detection of acute prosthetic joint infection, and exclusion of infection in chronic sterile prosthetic joint inflammation. PMID- 17334765 TI - The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model. AB - PURPOSE: Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with (18)F-fluoride ion, which localizes in regions of high osteoblastic activity, and (18)F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. METHODS: Fractures were created in the femurs of immunocompetent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, (18)F fluoride, and (18)F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. RESULTS: All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. (18)F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using (18)F FDG PET imaging at any time point. CONCLUSION: This study suggests that (18)F fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point and may have a role in the assessment of longitudinal fracture healing. PET scans using (18)F-FDG were not helpful in differentiating metabolic activity between successful and delayed bone healing. PMID- 17334766 TI - Endoscopic extraperitoneal radical prostatectomy: the University of Leipzig experience of 1,300 cases. AB - We herein review our experience with endoscopic extraperitoneal radical prostatectomy (EERPE) as a first line therapy for localized prostate cancer. A series of 1,300 patients underwent EERPE ("wide excision", standard nervesparing technique (nsEERPE), or intrafascial nsEERPE). The mean age of the patients was 63.3 years. Preoperative PSA mean value was 10.1 ng/ml. A total of 415 patients had undergone previous surgical procedure in the lower abdomen (n = 336) and prior surgery of the prostate (n = 79), respectively. The EERPE was employed in all cases without any specific selection criteria. Mean operative time was 153 (50-320) min. including lymphadenectomy with no conversion to open surgery. Seven intraoperative, 91 early and 4 late complications occurred. The transfusion rate was 0.9%. Positive surgical margins were found in 83 patients with pT2 stage (9.8%) and in 154 patients in pT3 stage (34.3%). The mean catheterization time was 6.2 days. The 12 month follow up indicated continence rate of 91.9% and potency rates of 34% in the unilateral nerve sparing group and 69.8% in the bilateral group. In the intrafascial nsEERPE group potency rates were 33.3% (unilateral) and 79.1% (bilateral) after 12 months. Postoperative positive surgical margins rate were 6.1% for pT2 and 20% for pT3 and the complications rate 4%. The results of this large series of 1,300 patients are promising. The recently introduced intrafascial nsEERPE further ameliorates the outcome of the procedure. PMID- 17334770 TI - Etiological differences between isolated lateral ventricle and the isolated fourth ventricle. PMID- 17334767 TI - Molecular staging of prostate cancer in the year 2007. AB - Numerous attempts towards improving patient management by molecular staging have been fruitless so far. No single molecular parameter is routinely analyzed in prostate cancer tissue. This may be partly due to genuine properties of prostate cancer that may make this tumor a difficult target. Furthermore, inherent logistical problems result in a shortage of prostate cancer tissue for research purposes. For the future, it can be hoped that the availability of more powerful molecular techniques in combination with better tissue archives will allow more rapid progress. Powerful DNA array and proteomics methods allow the systematic analysis of virtually all genes of a cancer on the DNA, RNA, and protein level. Although such approaches are sometimes labeled as "fishing expeditions," it cannot be totally disregarded that the simultaneous analysis of all genes has a high likelihood of identifying significant new information. In future, one of the major scientific challenges will be the validation of several potential biomarkers in large enough and clinically well-characterized patient cohorts. In particular, studies on needle core biopsies and hormone refractory cancers are imperatively needed for investigating the natural history of the disease or to discover potential predictive markers for radiation therapy and new therapeutic target genes to answer the clinically most important questions for optimal clinical decision making in prostate cancer patients: which patients will not require local therapy? If local therapy is needed, what is the treatment of choice? What medications should be given if metastases are present? PMID- 17334771 TI - Spine deformity in the ancient world. PMID- 17334772 TI - Stapled hemorrhoidopexy for prolapsed hemorrhoids in patients with liver cirrhosis; a preliminary outcome for 8-case experience. AB - PURPOSE: To investigate the efficacy and safety of stapled hemorrhoidopexy in treating prolapsed hemorrhoids in patients with liver cirrhosis. PATIENTS AND METHODS: Eight consecutive cases of patients with prolapsed hemorrhoids comorbid with liver cirrhosis, who had intractable response to other interventions, were enrolled in this retrospective study between January 2002 and June 2006 at our institute. Six patients (75%) had Child-Pugh class A liver cirrhosis, whereas only two patients (25%) had class B disease. Rectal varices were identified in three patients (37.5%), and esophageal varices were identified in six patients (75%). Concurrent rectal and esophageal varices existed in three patients (37.5%). The patients underwent stapled hemorrhoidopexy with Proximate PPH-03 in a lithotomy position under spinal/intravenous general anesthesia. RESULTS: There was no procedure-related mortality or major complications except hemorrhage. Two patients (25%) were complicated with postoperative staple-line bleeding, which was managed with conservative treatment without reoperation. There were no leading symptoms of relapsing during a follow-up period of at least 6 months. CONCLUSIONS: This study may prove that stapled hemorrhoidopexy is a feasible and safe approach for prolapsed hemorrhoids concurrent with liver cirrhosis. PMID- 17334773 TI - Human adult epidermal melanocytes cultured without chemical mitogens express the EGF receptor and respond to EGF. AB - We describe a novel chemical mitogen-free in vitro culture technique for obtaining pure melanocyte cultures using normal human adult epidermis as a source. The culture medium consists equal parts of the commercially available Keratinocyte Basal and AIM-V media (both from Gibco), as basal medium, which is supplemented with fetal bovine serum, bovine pituitary extract and recombinant human epidermal growth factor (EGF). Melanocytes harvested from human adult skin proliferate extensively and can be passaged serially up to 10-15 times using this medium. We have verified the identity of the cultured cells by tyrosinase mRNA expression and TRP-1 protein staining. Moreover, we showed that autologous human serum alone, without additional supplements is able to provide sufficient growth support for the cultured cells in the basal medium, making this culture technique suitable for autologous melanocyte transplantation. In this culture system normal human adult melanocytes expressed both EGF receptor (EGFR) mRNA and protein and EGF showed a dose dependent mitogenic effect on the cells. EGF itself had no significant influence on EGFR mRNA expression. PMID- 17334774 TI - Occupational exposure to ionizing and non-ionizing radiation and risk of non Hodgkin lymphoma. AB - OBJECTIVE: To investigate the association between occupational exposure to ionizing, ultraviolet (UV), radiofrequency (RF) and extremely low frequency (ELF) radiation and risk of developing non-Hodgkin lymphoma (NHL) in a population-based case-control study. METHODS: The study population consisted of 694 NHL cases, first diagnosed between 1 January 2000 and 31 August 2001, and 694 controls from two regions in Australia, matched by age, sex and region of residence. A detailed occupation history was first obtained using a lifetime calendar and a telephone interview. Exposure to radiation was then assessed using a Finnish job-exposure matrix (FINJEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models that included the matching variables as covariates. RESULTS: For ionizing radiation, the ORs were close to unity. For UV and ELF radiation, the highest exposed group of workers had ORs of 1.32 (95% CI=0.96-1.81) and 1.25 (95% CI=0.91-1.72), respectively. For UV radiation there was a positive dose-response when exposure was lagged by 5 and 10 years (P for trend 0.04 for both lag periods). Workers in the upper tertile of exposure for RF radiation had an OR of 3.15 (95% CI=0.63-15.87), but the estimate was based on very small numbers. CONCLUSIONS: Our results do not provide support for an association between NHL and occupational exposure to ionizing or ELF radiation. For UV radiation, our findings are consistent with a weak positive association. Further investigation focusing on UV and RF radiation and NHL is required. PMID- 17334775 TI - Adrenergic effects on adrenocortical cortisol response to incremental exercise to exhaustion. AB - This study evaluated the influence of adrenergic factors on the cortisol response to maximal exercise in endurance-trained men. This was achieved by testing healthy young men during exercise while varying both the condition of beta adrenergic blockage and the presence of a well-controlled simulated competitive environment to simulate activity of the sympatho-adrenal systems. Subjects (n = 10) performed maximal exercise (running) to exhaustion on a treadmill during four conditions: (1) placebo non-competitive [PNon] (2) after administration of 80 mg propranolol non-competitive [betaNon] (3) in a simulated competition after a placebo intake [PCom], and (4) in a simulated competition after propranolol intake [betaCom]. Blood samples were obtained before (pre-) and 3 min after (post ) exercise and assayed for cortisol (C). The data were analyzed with a multi factorial repeated measures ANCOVA procedure. Statistical analysis revealed a significant three-way interaction for the drug versus competition versus sampling time effects (P < 0.05). Post-hoc tests revealed that the pre-exercise cortisol values did not differ significantly among the conditions. Cortisol did increase from pre- to post-exercise in all experimental conditions (P < 0.01), and the magnitudes of increase in the PCom, betaNon and betaCom conditions were greater than that of the PNon condition. Furthermore, the cortisol increases for both beta-blockage conditions post-exercise (betaNon, betaCom) did not differ from one another (P > 0.05). The findings suggest beta-adrenergic blockage and competitive conditions enhance the exercise cortisol response. In combination, however, these conditions do not act in an additive fashion. This suggests that perhaps there may be two separate influences or mechanisms (i.e., excitatory, inhibitory) on the adrenergic control of adrenocortical function, or a sympathetic compensation for beta-blockage during exhaustive maximal exercise. Furthermore, the data suggests a possible "ceiling" on the hypothalamic-pituitary-adrenal axis response to exercise in endurance-trained men. PMID- 17334776 TI - Age- and gender-related differences of the immune function in a murine model of hemorrhagic shock: IL-10 restores immunodepression in aged females without reduction of mortality. AB - INTRODUCTION: Interleukin-10 (IL-10) treatment has been shown to have beneficial effects on the immune function after hemorrhagic shock and to improve survival after subsequent sepsis in young male mice, but not in young females. Although it was demonstrated that the immune function under these conditions is reversed with age, it remains unclear whether the observed gender-related effect of IL-10 treatment continues to exist in aged mice. MATERIALS AND METHODS: Aged male and female CBA/J mice (18-19 months) were subjected to hemorrhage (35 +/- 5 mmHg for 90 min) or sham operation. At resuscitation, each received either 10-microg recombinant murine (rm)IL-10 or placebo i.p. At 48 h after resuscitation, either the mice were killed and the plasma, splenic macrophages (sM phi), and splenocytes were harvested or polymicrobial sepsis was induced by cecal ligation and puncture (CLP). After CLP, either survival over 10 days was determined or, 4 h after CLP, tissues were again harvested and cytokine-released in vitro were assessed by enzyme-linked immunosorbent assay. RESULTS: Early IL-10 treatment restored depressed proinflammatory immune response (TNF-alpha, IL-1 beta) and Th1 response of splenocytes in aged females after hemorrhage, whereas having no effects or having suppressive effects in aged males. Subsequent sepsis combined with placebo treatment led to a significant suppression of proinflammatory cytokine release of sM phi and a significant increase of Th2 response in both males and females associated with high mortality (80-100%, respectively) after CLP. These effects were not influenced by early rmIL-10 treatment. CONCLUSION: After hemorrhage, early rmIL-10 treatment restored immune function in aged females, but not in males. However, in contrast to young mice, rmIL-10 treatment had no effect on survival and immune function after CLP in aged mice. PMID- 17334777 TI - Calcium-dependent transcription of cytokine genes in T lymphocytes. AB - The increase in intracellular calcium ion concentration is a general signaling mechanism used in many biological systems. In T lymphocytes, calcium is essential for activation, differentiation, and effector functions. In this study, we will summarize recent developments of how intracellular calcium concentrations are modified in T cells to affect the activity of three major calcium-dependent transcriptional effectors, i.e., NFAT, MEF2, and DREAM, involved in cytokine gene expression. PMID- 17334778 TI - Calcium indicator loading of neurons using single-cell electroporation. AB - Studies of subcellular Ca(2+) signaling rely on methods for labeling cells with fluorescent Ca(2+) indicator dyes. In this study, we demonstrate the use of single-cell electroporation for Ca(2+) indicator loading of individual neurons and small neuronal networks in rat neocortex in vitro and in vivo. Brief voltage pulses were delivered through glass pipettes positioned close to target cells. This approach resulted in reliable and rapid (within seconds) loading of somata and subsequent complete labeling of dendritic and axonal arborizations. By using simultaneous whole-cell recordings in brain slices, we directly addressed the effect of electroporation on neurons. Cell viability was high (about 85%) with recovery from the membrane permeabilization occurring within a minute. Electrical properties of recovered cells were indistinguishable before and after electroporation. In addition, Ca(2+) transients with normal appearance could be evoked in dendrites, spines, and axonal boutons of electroporated cells. Using negative-stains of somata, targeted single-cell electroporation was equally applicable in vivo. We conclude that electroporation is a simple approach that permits Ca(2+) indicator loading of multiple cells with low background staining within a short amount of time, which makes it especially well suited for functional imaging of subcellular Ca(2+) dynamics in small neuronal networks. PMID- 17334779 TI - Roles of Na+/H+ exchange in regulation of p38 mitogen-activated protein kinase activity and cell death after chemical anoxia in NIH3T3 fibroblasts. AB - Activation of Na(+)/H(+) exchange (NHE) plays a major role in cell death following ischemia/hypoxia in many cell types, yet counteracts apoptotic cell death after other stimuli. To address the role of NHE activity in regulation of cell death/survival, we examined the causal relationship between NHE, p38 mitogen activated protein kinase (MAPK), ERK1/2, p53, and Akt activity, and cell death, after chemical anoxia in NIH3T3 fibroblasts. The NHE1 inhibitor 5'-(N-ethyl-N isopropyl) amiloride (EIPA) (5 muM), as well as removal of extracellular Na(+) [replaced by N-methyl-D: -glucamine (NMDG(+))], prevented recovery of intracellular pH (pH(i)) during chemical anoxia (10 mM NaN(3) +/- 10 mM glucose), indicating that activation of NHE was the dominating mechanism of pH(i) regulation under these conditions. NHE activation by chemical anoxia was unaffected by inhibitors of p38 MAPK (SB203580) and extracellular signal regulated kinase (ERK) (PD98059). In contrast, chemical anoxia activated p38 MAPK in an NHE-dependent manner, while ERK1/2 activity was unaffected. Anoxia-induced cell death was caspase-3-independent, mildly attenuated by EIPA, potently exacerbated by SB203580, and unaffected by PD98059. Ser(15) phosphorylation of p53 was increased by anoxia in an NHE- and p38 MAPK-independent manner, while Akt activity was unaffected. It is suggested that after chemical anoxia in NIH3T3 fibroblasts, NHE activity is required for activation of p38 MAPK, which in turn protects the cells against anoxia-induced death. In spite of this, NHE inhibition slightly attenuates anoxia-induced cell death, likely due to the involvement of NHE in other anoxia-induced death pathways. PMID- 17334780 TI - Regulation of ubiquitin-proteasome system, caspase enzyme activities, and extracellular proteinases in rat soleus muscle in response to unloading. AB - In the present study, we determined the impact of 5 and 10 days of muscle deconditioning induced by hindlimb suspension (HS) on the ubiquitin-proteasome system of protein degradation and caspase enzyme activities in rat soleus muscles. A second goal was to determine whether activities of matrix metalloproteinase-2/9 (MMP-2/9) and urokinase-type/tissue-type plasminogen activator (PAs) were responsive to HS. As expected, HS led to a pronounced atrophy of soleus muscle. Level of ubiquitinated proteins, chymotrypsin-like activity of 20S proteasome, and Bcl-2-associated gene product-1 protein level were all transitory increased in response to 5 days of HS. These changes may thus potentially account for the decrease in muscle mass observed in response to 5 days of HS. Caspase-3 activity was significantly increased throughout the experimental period, whereas activities of caspase-6, another effector caspase, and caspase-9, the mitochondrial-dependent activator of both caspase-3 and -6, were only increased in response to 10 days of HS. This suggests that caspase-3 may be regulated through mitochondrial-independent and mitochondrial-dependent mechanisms in response to HS. Finally, MMP-2/9 activities remained unchanged, whereas PAs activities were increased after 5 days of HS. Overall, these data suggest that time-dependent regulation of intracellular and extracellular proteinases are important in setting the new phenotype of rat soleus muscle in response to HS. PMID- 17334781 TI - Differentially expressed cDNAs at the early stage of banana ripening identified by suppression subtractive hybridization and cDNA microarray. AB - The banana (Musa acuminate L. AAA group) fruit undergoes a postharvest ripening process, which plays an important role in improving the quality and extending the shelf life of bananas. To manipulate postharvest banana ripening, a better understanding of the mechanism of postharvest ripening is necessary. The isolation of mRNA transcripts encoding proteins associated with the ripening process is a powerful tool for this purpose. To isolate differentially expressed genes at the early stage of postharvest banana ripening, a forward suppression subtractive hybridization (SSH) cDNA library was constructed. SSH was performed with cDNA from banana fruit on the day of harvest as the "driver" and cDNA from banana fruit 2 days postharvest (DPH) as the "tester." A total of 289 clones in the SSH library were sequenced. BLASTX results revealed that 191 cDNAs had significant sequence homologies with known sequences in the NCBI database. Of the 191 cDNAs, 138 were singletons, and 53 belonged to divergent clusters containing 2-8 sequences. The identified cDNAs encoded proteins involved in cellular processes such as: metabolism; protein destination and storage; protein synthesis; signal transduction; transport and intracellular traffic; cell structure, growth, and division; transcription and post-transcription; and disease and defense. To characterize differentially expressed cDNAs in the SSH library, cDNA microarray analysis was conducted. A total of 26 cDNAs in the 2-DPH banana fruit were found to be up-regulated and these results were confirmed by using reverse transcriptase-polymerase chain reaction (RT-PCR). The information generated in this study provides new clues to aid in the understanding of banana ripening. PMID- 17334782 TI - Boron deficiency decreases plasmalemma H+-ATPase expression and nitrate uptake, and promotes ammonium assimilation into asparagine in tobacco roots. AB - The effects of short-term boron deficiency on several aspects (growth, biomass allocation, metabolite concentrations, gene expression, enzyme activities) related with nitrate assimilation were studied in tobacco (Nicotiana tabacum L.) plants in order to know the early changes caused by this mineral deficiency. For this purpose, plants were grown hydroponically in a nutrient solution supplemented with 10 microM boron and then transferred to a boron-free medium for 1-5 days. Nitrate concentration decreased in both leaves and roots under boron deficiency, which was not observed in control plants. This correlated with the lower net nitrate uptake rate found in boron-deficient plants when compared to boron-sufficient ones. Results suggest that boron deficiency decreases net nitrate uptake by declining the activity of nitrate transporters rather than affecting their transcript levels. This is supported by a drop in the levels of root PMA2 transcript during the boron deficient treatment, which could lead to a decrease in the plasma membrane H+-ATPase activity necessary to get protons out of cell for the cotransport with nitrate inwards. In addition, boron deficiency led to an increase in root Asn content and a decline in glutamine synthetase activity when compared to control plants, which suggest that this mineral deficiency may promote ammonium assimilation via asparagine synthetase in tobacco roots. PMID- 17334784 TI - Varicella vaccination in Europe: are we ready for a universal childhood programme? AB - Safe and effective vaccines against varicella zoster virus (VZV), the aetiological agent of varicella and shingles, have been available in Europe for the last 5-10 years. The USA has had a universal childhood vaccination policy since 1995 and this has resulted in a dramatic decrease in the incidence, morbidity and mortality related to varicella. The economic and medical burden of VZV has led to discussions regarding both the desirability and feasibility of a similar routine immunisation policy for all European children. This article examines the epidemiology of varicella in Europe and how the data emerging from the USA can be used to achieve adequate prevention of the disease. It looks into the current evidence of the health economic evaluation of universal varicella vaccination and explores the concerns surrounding such a policy, including the postulated impact on the incidence of zoster. In conclusion, the Society of Independent European Vaccination Experts (SIEVE) recommends that the immunisation of susceptible adolescents needs to be urgently implemented, in addition to the current recommendations targeting high-risk patients, their close contacts with a negative history of varicella and seronegative health-care workers. A universal policy, optimally incorporating a two-dose schedule, will be needed to finally reduce the burden of disease of varicella from a societal point of view. The SIEVE recommends the implementation of such a policy as soon as financially and practically possible. PMID- 17334785 TI - Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co operative Oncology Group. AB - PURPOSE: To scrutinize published data from small mono-centric studies and case reports which implicated high response rates and promising survival times for a combination therapy consisting of epifocal dinitrochlorobenzene (DNCB) and dacarbazine (DTIC) for metastasized melanoma. This therapy merges the effects of an allergic contact dermatitis elicited at the site of a cutaneous metastasis, and systemic chemotherapy. METHODS: We performed a retrospective survey with nine German centers and evaluated 72 patients treated from 1993 to 2005. RESULTS: The objective response rate in stage III melanoma (n = 39) was 62%. In contrast, only 9% objective responses were observed in 33 stage IV patients. Interestingly, more than half of patients with objective remissions remained progression-free for more than 1 year irrespective of the stage of disease. CONCLUSIONS: Epifocal DNCB combined with DTIC is effective in patients with regionally metastasized melanoma not amenable to surgery or isolated limb perfusion, whereas in stage IV disease in spite of few durable remissions the addition of DNCB does not improve the therapeutic efficacy of DTIC. PMID- 17334786 TI - Trypanosoma (Herpetosoma) kuseli sp. n. (Protozoa: Kinetoplastida) in Siberian flying squirrels (Pteromys volans). AB - All trypanosome species classified in the subgenus Herpetosoma in sciurid hosts have been recorded from ground and tree squirrels to date, but not from any flying squirrels. We describe in this paper a novel trypanosome species, Trypanosoma (Herpetosoma) kuseli sp. n., from Siberian flying squirrels (Pteromys volans) imported from China, and compare it with T. (H.) otospermophili in Richardson's ground squirrels (Spermophilus richardsonii) and Columbian ground squirrels (Spermophilus columbianus) from the USA. Due to a short free flagellum, the new species appeared stumpy compared with T. otospermophili (length of free flagellum 7.0 +/- 0.8 microm, total length 32.1 +/- 0.8 microm, n = 13 and length of free flagellum 15.5 +/- 1.6 microm, total length 35.9 +/- 1.0 microm, n = 13, respectively). Another conspicuous morphological feature of the new species was an anteriorly positioned kinetoplast, found approximately at the midpoint between the nucleus and the posterior end. These characters have not been recorded from any squirrel Herpetosoma trypanosome species. Comparison of the nucleotide sequences of the small and large subunit rRNA genes indicated that T. kuseli sp. n. was more homologous to T. otospermophili than murid Herpetosoma species, such as T. grosi, T. lewisi, T. musculi, T. microti and T. evotomys. PMID- 17334783 TI - Transcriptional analysis of petal organogenesis in Gerbera hybrida. AB - Understanding of the molecular interplay, which determines early steps of flower formation has grown considerably during last years. In contrast, genetic actions responsible for how flower organs acquire their size and shape at later phases of organogenesis are still poorly understood. We have exploited the large and anatomically simple Gerbera (Gerbera hybrida var. Terra regina) ray flower petals to describe transcriptional changes during organogenesis. Gerbera 9 K cDNA microarray was utilized to profile gene expression at six different developmental stages of petal organogenesis, at the earliest stage expansion of petals is starting and at the latest stage petals have reached their final size and shape. Genes potentially participating in petal opening were identified based on the similarity in expression with a known marker gene. Our results showed characteristic sets of genes expressed during the cell division and cell expansion phases of petal development. Interestingly, there was a transition stage during which neither cell division nor cell expansion marker genes were abundantly expressed. Moreover, constitutive expression of late petal specific genes indicates that they participate in petal organogenesis throughout the development and they are not involved in stage specific switch points. PMID- 17334787 TI - Impact of foliar herbivory on the development of a root-feeding insect and its parasitoid. AB - The majority of studies exploring interactions between above- and below-ground biota have been focused on the effects of root-associated organisms on foliar herbivorous insects. This study examined the effects of foliar herbivory by Pieris brassicae L. (Lepidoptera: Pieridae) on the performance of the root herbivore Delia radicum L. (Diptera: Anthomyiidae) and its parasitoid Trybliographa rapae (Westwood) (Hymenoptera: Figitidae), mediated through a shared host plant Brassica nigra L. (Brassicaceae). In the presence of foliar herbivory, the survival of D. radicum and T. rapae decreased significantly by more than 50%. In addition, newly emerged adults of both root herbivores and parasitoids were significantly smaller on plants that had been exposed to foliar herbivory than on control plants. To determine what factor(s) may have accounted for the observed results, we examined the effects of foliar herbivory on root quantity and quality. No significant differences in root biomass were found between plants with and without shoot herbivore damage. Moreover, concentrations of nitrogen in root tissues were also unaffected by shoot damage by P. brassicae larvae. However, higher levels of indole glucosinolates were measured in roots of plants exposed to foliar herbivory, suggesting that the development of the root herbivore and its parasitoid may be, at least partly, negatively affected by increased levels of these allelochemicals in root tissues. Our results show that foliar herbivores can affect the development not only of root-feeding insects but also their natural enemies. We argue that such indirect interactions between above- and below-ground biota may play an important role in the structuring and functioning of communities. PMID- 17334788 TI - Pre-pubertal induction of experimental diabetes protects against early renal macrophage infiltration. AB - The present study was undertaken to identify whether the age at induction of experimental diabetes modifies macrophage infiltration in the kidney. Renal macrophage infiltration was studied 10 days after the induction of experimental diabetes in 4-week-old pre-pubertal and 12-week-old adult male rats of normotensive [Wistar-Kyoto (WKY) rats] and hypertensive (spontaneously hypertensive rats, SHRs) background. Renal macrophage infiltration was evaluated by immunohistochemistry for ED1. Plasma glucose levels were similar in all diabetic groups. Adult SHRs were hypertensive, and induction of diabetes did not alter blood pressure (BP) in any group. Induction of diabetes in pre-pubertal rats did not induce macrophage infiltration in the kidney. However, in adult rats, tubulointerstitial macrophage infiltration was increased in both WKY (22.86 +/- 3.93 vs 7.86 +/- 2.16 per high-power field, P < 0.001) and SHR (26.41 +/- 5.91 vs 11.48 +/- 1.23, P < 0.001) groups after induction of diabetes. Glomerular macrophage infiltration was also increased after induction of diabetes in the adult WKY group (1.83 +/- 0.50 vs 1.16 +/- 0.26 per glomerular cross section, P = 0.029), which was not significant in the adult SHRs (2.52 +/- 0.34 vs 1.95 +/- 0.35). We conclude that the pre-pubertal induction of diabetes apparently protects against early renal macrophage infiltration, while the induction of diabetes in adults induces exaggerated macrophage infiltration in the kidney. PMID- 17334789 TI - Outcomes of children with proliferative lupus nephritis: the role of protocol renal biopsy. AB - Outcomes in children with proliferate lupus nephritis (PLN) show 9-15% progress to end-stage renal disease (ESRD) at 5 years. Immunosuppression improves outcome, but significant side effects are possible. Clinical and laboratory analyses are poor predictors of class and progression in PLN. We describe 28 patients with systemic lupus erythematosus (SLE), between 1990 and 2005, whose initial biopsy (Bx1) showed PLN and who received nine monthly doses of intravenously administered cyclophosphamide (CYP) (500-750 mg/m(2) up to 1 g to maintain their absolute neutrophil count (ANC) > 3,000). Continued therapy with additional quarterly intravenous (i.v). administration of CYP was dictated by repeat renal biopsy (Bx2). Bx1 was done 1 +/- 1.6 years after diagnosis of SLE. Bx2 showed histological improvement by WHO classification in 20/25 children; 3/25 were unchanged, 1/25 was categorized as new class V, and 1/25 was worse. Four patients (14%) had infectious complications requiring hospitalization (one of these died). Mean follow-up (f/u) after Bx2 was 3.5 +/- 2.3 years. At last follow-up, 26 patients had normal glomerular filtration rate (GFR), with a mean of 126 +/- 42.8 ml/min per 1.73 m(2) body surface area, one non-compliant patient had ESRD, and one had chronic renal failure. At last follow-up, most patients had minimal to no proteinuria. Clinical and biopsy results greatly improved after 9 monthly intravenously administered CYP pulses in most children with class IV PLN. Those who did not improve are at risk for flares and progression of disease. The tailoring of therapies based on findings from a biopsy after induction may improve outcomes. PMID- 17334791 TI - Modic changes following lumbar disc herniation. AB - Only a small proportion (20%) of patients with LBP can be diagnosed based on a patho-anatomical entity. Therefore, the identification of relevant subgroups, preferably on a patoanatomical basis, is strongly needed. Modic changes have been described by several authors as being closely linked with LBP. The aims of this study were to describe the prevalence of Modic changes, their development as well as their association to LBP, previous disc contour, and surgery in patients with previous severe sciatica. This is a longitudinal cohort study where the patients were recruited from an RCT comparing two active conservative treatments, the 181 patients, who at baseline had radicular pain in or below the knee; all underwent a physical examination and MRI. MRI's, pain history and physical examination of 166 patients were obtained at follow-up 14 months later. The prevalence of Modic changes type 1 increased from 9% at baseline to 29% at follow-up. At that time, a strong association between Modic changes and non-specific LBP was noted. Apparently, Modic changes type 1 was more strongly associated with non-specific lumbar pain than Modic changes type 2. The development of new Modic changes was closely related to the level of a previous disc herniation. A lumbar disc herniation is a strong risk factor for developing Modic changes (especially type 1) during the following year. Furthermore, Modic changes are strongly associated with LBP. PMID- 17334790 TI - Genetic diversity of ectomycorrhizal Basidiomycetes from African and Indian tropical rain forests. AB - Ectomycorrhizal (ECM) fungi have a worldwide distribution. However, the ecology of tropical ECM fungi is poorly documented, limiting our understanding of the symbiotic associations between tropical plants and fungi. ECM Basidiomycete diversity was investigated for the first time in two tropical rain forests in Africa (Western Upper Guinea) and in Asia (Western Ghats, India), using a fragment of the mitochondrial large subunit rRNA gene to type 140 sporocarps and 54 ectomycorrhizas. To evaluate taxonomic diversity, phylogenetic analyses were performed, and 40 sequences included from identified European specimens were used as taxonomic benchmarks. Five clades were recovered corresponding to six taxonomic groups: boletoids, sclerodermatoids, russuloids, thelephoroids, and a clade grouping the Amanitaceae and Tricholomataceae families. Our results revealed that the Russulaceae species display a great diversity with several putative new species, especially in Guinea. Other taxonomic issues at family/section levels are also briefly discussed. This study provides preliminary insights into taxonomic diversity, ECM status, and biogeographic patterns of ECM fungi in tropical two rain forest ecosystems, which appear to be as diverse as in temperate and boreal forests. PMID- 17334792 TI - Is anterior release necessary in severe scoliosis treated by posterior segmental pedicle screw fixation? AB - With the advent of segmental pedicle screw fixation that enables more powerful corrective forces, it is postulated that an additional anterior procedure may be unnecessary even in severe deformities. The purpose of this paper is to evaluate the results of a posterior procedure alone using segmental pedicle screw fixation in severe scoliotic curves over 70 degrees . Thirty-five scoliosis patients treated by pedicle screw fixation and rod derotation were retrospectively analyzed after a minimum follow-up of 2 years (range 2-10.4). The mean age of patients was 15.3 years (range 9.8-34.2). Diagnoses were idiopathic scoliosis in 29, neuromuscular scoliosis in 3 and scoliosis associated with Marfan syndrome in 3. Scoliosis consisted of single thoracic curve in 18, double thoracic in 5 and double major in 12. Twenty-five patients showed a major thoracic curve greater than 70 degrees (range 70-100), and different ten patients showed a major lumbar curve greater than 70 degrees (range 70-105), pre-operatively. The deformity angle, lowest instrumented vertebral tilt (LIVT) and spinal balance were measured. Pre-operatively there were nine patients with coronal decompensation. The pre-operative thoracic curve of 80 +/- 9 degrees with the flexibility of 45 +/- 11% (45 +/- 11 degrees in side-bending film) was corrected to 27 +/- 10 degrees at the most recent follow-up, showing a correction of 66% (53 degrees) and loss of correction of 3.0% (3.7 degrees). The pre-operative lumbar curve of 79 +/- 12 degrees with the flexibility of 62 +/- 14% (30 +/- 11 degrees in side bending film) was corrected to 33 +/- 14 degrees at the most recent follow-up [59% (46 degrees) curve correction, 3.5% (3.0 degrees) loss of curve correction]. The pre-operative LIVT of 30 +/- 8 degrees was corrected to 11 +/- 6 degrees, showing a correction of 62% (19 degrees). Residual coronal decompensation was observed in three patients postoperatively. Pre-operative thoracic kyphosis of 27 degrees (range 0-82) improved postoperatively to 31 degrees (range 14-53). In conclusion, posterior segmental pedicle screw fixation without anterior release in severe scoliosis had satisfactory deformity correction without significant loss of curve correction. In this series a posterior procedure alone obviated the need for the anterior release and avoided complications related anterior surgery. PMID- 17334793 TI - Management of odontoid fractures with percutaneous anterior odontoid screw fixation. AB - Minimally invasive techniques have revolutionized the management of a variety of spinal disorders. The authors of this study describe a new instrument and a percutaneous technique for anterior odontoid screw fixation, and evaluate its safety and efficacy in the treatment of patients with odontoid fractures. Ten patients (6 males and 4 females) with odontoid fractures were treated by percutaneous anterior odontoid screw fixation under fluoroscopic guidance from March 2000 to May 2002. Their mean age at presentation was 37.2 years (with a range from 21 to 55 years). Six cases were Type II and four were Type III classified by the Anderson and D'Alonzo system. The operation was successfully completed without technical difficulties, and without any soft tissue complications such as esophageal injury. No neurological deterioration occurred. Satisfactory results were achieved in all patients and all of the screws were in good placement. After a mean follow-up of 15.7 months (range 10-25 months), radiographic fusion was documented for 9 of 10 patients (90%). Neither clinical symptoms nor screw loosening or breakage occurred. Our preliminary clinical results suggest that the percutaneous anterior odontoid screw fixation procedure using a new instrument and fluoroscopy is technically feasible, safe, useful, and minimally invasive. PMID- 17334794 TI - The spinal cord dura mater reaction to nitinol and titanium alloy particles: a 1 year study in rabbits. AB - This investigation was undertaken to simulate in an animal model the particles released from a porous nitinol interbody fusion device and to evaluate its consequences on the dura mater, spinal cord and nerve roots, lymph nodes (abdominal para-aortic), and organs (kidneys, spleen, pancreas, liver, and lungs). Our objective was to evaluate the compatibility of the nitinol particles with the dura mater in comparison with titanium alloy. In spite of the great use of metallic devices in spine surgery, the proximity of the spinal cord to the devices raised concerns about the effect of the metal debris that might be released onto the neural tissue. Forty-five New Zealand white female rabbits were divided into three groups: nitinol (treated: N = 4 per implantation period), titanium (treated: N = 4 per implantation period), and sham rabbits (control: N = 1 per observation period). The nitinol and titanium alloy particles were implanted in the spinal canal on the dura mater at the lumbar level L2-L3. The rabbits were sacrificed at 1, 4, 12, 26, and 52 weeks. Histologic sections from the regional lymph nodes, organs, from remote and implantation sites, were analyzed for any abnormalities and inflammation. Regardless of the implantation time, both nitinol and titanium particles remained at the implantation site and clung to the spinal cord lining soft tissue of the dura mater. The inflammation was limited to the epidural space around the particles and then reduced from acute to mild chronic during the follow-up. The dura mater, sub-dural space, nerve roots, and the spinal cord were free of reaction. No particles or abnormalities were found either in the lymph nodes or in the organs. In contact with the dura, the nitinol elicits an inflammatory response similar to that of titanium. The tolerance of nitinol by a sensitive tissue such as the dura mater during the span of 1 year of implantation demonstrated the safety of nitinol and its potential use as an intervertebral fusion device. PMID- 17334795 TI - C7 decancellisation closing wedge osteotomy for the correction of fixed cervico thoracic kyphosis. AB - Our objective is to report on the clinical and radiological outcome following a decancellisation closing wedge osteotomy for the correction of fixed cervico thoracic kyphosis in patients with ankylosing spondylitis. The only treatment available for severe fixed flexion deformity of the cervical spine in these patients is an extension osteotomy. Traditionally an anterior opening, posterior closing wedge osteotomy is performed with or without internal fixation. We describe a decancellisation closing wedge osteotomy of C7 accompanied by secure segmental internal fixation. Eight patients operated between 1990 and 2003 with mean age of 54 years and minimum follow up of 2 years were retrospectively evaluated. Restoration of normal forward gaze was achieved in all patients. No patient suffered spinal cord injury or permanent nerve root palsy. There was no loss of correction or pseudarthrosis at final follow up. C7 decancellisation closing wedge osteotomy supplemented with secure segmental internal fixation in experienced hands provides a safe and effective treatment for fixed cervico thoracic kyphosis in patients with ankylosing spondylitis. PMID- 17334796 TI - The interactions of cobalt(II) with mitochondria from rat liver. AB - The interactions of Co(2+) with mitochondria have been investigated. The results indicate that Co(2+) inhibits ATP synthesis. Further investigations into ATP synthesis mechanisms indicated that inhibition is due to the opening of a transmembrane pore. The opening of this pore causes the collapse of the high energy intermediate where, under a pH and a potential gradient, the energy is stored and subsequently utilized to form ATP from ADP. PMID- 17334797 TI - A dinuclear monofunctional platinum(II) complex with an aromatic linker shows low reactivity towards glutathione but high DNA binding ability and antitumor activity. AB - Multinuclear Pt(II) complexes represent a novel class of antitumor agents. In this work, a dinuclear monofunctional Pt(II) complex {[cis Pt(NH(3))(2)Cl](2)(4,4'-methylenedianiline)}(NO(3))(2) (1) was synthesized and characterized by (1)H NMR, electrospray mass spectrometry, and elemental analysis. The 2D [(1)H,(15)N] heteronuclear single quantum coherence NMR spectra of (15)N-labeled 1 revealed that the cationic core of this water-soluble complex hardly hydrolyzes in aqueous solution and reacts very slowly with glutathione. Hydrolysis appears not to be an essential step for the formation of Pt-guanosine 5'-monophosphate (5'-GMP) or Pt-DNA adducts because the complex can react readily with 5'-GMP and partially transform B-DNA into its Z form. Such properties are desired to achieve the goal of enhancing cytotoxicity and lowering side effects of Pt(II) complexes. In fact, complex 1 is highly cytotoxic against the murine leukemia (P-388) and the human non-small-cell lung cancer (A-549) cell lines, and it is more cytotoxic than cisplatin at most concentrations tested. PMID- 17334798 TI - Functions of mesolimbic dopamine: changing concepts and shifting paradigms. PMID- 17334799 TI - Medial forebrain bundle stimulation evokes endocannabinoid-mediated modulation of ventral tegmental area dopamine neuron firing in vivo. AB - RATIONALE: Endocannabinoid-mediated forms of transient synaptic depression have been described in several brain structures, including the dopaminergic ventral tegmental area (VTA). However, their functional and/or behavioural correlates are yet to be determined. OBJECTIVES: The present study was designed to investigate whether back-propagating action potentials in dopamine (DA) neurons, evoked by the stimulation of the medial forebrain bundle (MFB), could trigger endocannabinoid-mediated forms of synaptic modulation. The MFB contains axons ascending from DA neurons to the nucleus accumbens and other forebrain structures, and its stimulation is rewarding because it elicits intra-cranial self-stimulation. MATERIALS AND METHODS: Single cell extracellular recordings were carried out from anti-dromically identified VTA DA neurons in chloral hydrate anesthetized rats. RESULTS: DA neurons responded to MFB stimulation (1 s, 20-80 Hz) with a frequency-dependent increase in spontaneous firing rate, which was enhanced by the cannabinoid type-1 receptor antagonist SR141716A (1 mg/kg) and depressed by the agonist WIN55212-2 (0.125 mg/kg). Increasing brain levels of the endocannabinoid anandamide by blocking its major hydrolysing enzyme, fatty acid amide hydrolase, with URB597 (0.1 mg/kg) was ineffective, whereas blockade of the endocannabinoid membrane transporter with UCM707 (1 mg/kg) enhanced post stimulus firing rate. CONCLUSIONS: Our study indicates that stimulation of the MFB evokes an endocannabinoid-mediated short-term modulation of DA neuron activity. Thus, endocannabinoids might play an important role in the mechanisms underlying the rewarding properties of MFB stimulation. PMID- 17334801 TI - Recommendations for the reporting of pleural mesothelioma. PMID- 17334800 TI - Recommendations for the reporting of surgically resected specimens of colorectal carcinoma. PMID- 17334802 TI - Recommendations for the reporting of fallopian tube neoplasms. PMID- 17334806 TI - Abstracts of the 50th Annual Meeting and Postgraduate Course of the Society for Pediatric Radiology. April 17-21, 2007. Miami, Florida, USA. PMID- 17334805 TI - A novel gene derived from a segmental duplication shows perturbed expression in Alzheimer's disease. AB - Alzheimer's disease (AD) is a disabling neurodegenerative disorder with onset commonly in late life. Three genes have been identified causing earlier onset AD, and a fourth has been shown to be a risk factor for late onset AD (LOAD), while many more yet unrecognized genes are thought to contribute to susceptibility. Many studies have reported linkage to LOAD on human chromosome 10, where we have identified a parent of origin effect [Bassett SS, Avramopoulos D, Perry RT, Wiener H, Watson B Jr, Go RC, Fallin MD. Am J Med Genet B Neuropsychiatr Genet 141:537-540, (2006), Bassett SS, Avramopoulos D, Fallin D. Am J Med Genet 114:679 686, (2002)]. In this paper, we report on a gene in this region that shows reduced expression with increasing age, reduced expression in females across ages, and further reduction in LOAD patients. In concordance with the observed parent of origin effect on the linkage, this reduction is more pronounced in patients with an affected mother. We discovered this gene while studying the alkaline ceramidase gene (ASAH2); it is a partial paralog of ASAH2, and we call it ASAH2L. It is the result of a partial duplication of ASAH2 on chromosome 10q11.23, just downstream from the sequence with promoter activity. ASAH2L has a polymorphic start codon with a single nucleotide change of the original ASAH2 sequence plus other putative translation start sites that might produce novel proteins. It is expressed in all the tissues we tested including the brain and is an interesting example of the generation of a new gene. Comparison of primate and other mammal genomes suggests that ASAH2L is human specific. Further research would be necessary to determine the function of the ASAH2L transcript and explore any possible involvement in neurodegeneration. PMID- 17334803 TI - Ontogenesis of human cerebellar cortex and biopathological characterization in sudden unexplained fetal and infant death. AB - The aims of this study were to investigate in the human cerebellar cortex the structural and biological ontogenetic features, the possible presence of alterations in cases of sudden unexplained fetal and infant death, and the involvement of the maternal cigarette smoking in developmental abnormalities. We analyzed 52 brains of fetal and infant death victims, aged from the second gestational trimester to 12th postnatal month. In the cerebellar cortex we evaluated, besides the morphological aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, proliferating cell nuclear antigen, and apoptosis) as well as the presence of the neurotransmitter somatostatin, which is strongly implicated in central nervous system differentiation, and of EN2 gene. The observed features of the cerebellar cortex, mainly confined to the transient external granular layer, were high proliferative activity and high expression of both somatostatin and EN2 gene in prenatal life and high apoptotic index after birth. In 41% of the sudden unexplained death victims, in the greater part with smoking mothers, we observed different biopathological alterations of the cerebellar cortex. Maternal smoking is increasingly being demonstrated to be one of the main contributors to developmental neurological alterations in the offspring. PMID- 17334811 TI - Prostate volume modifies the association between obesity and prostate cancer or high-grade prostatic intraepithelial neoplasia. AB - The relationship between obesity and prostate cancer remains unclear. We investigated the effect of prostate volume on the obesity and prostate cancer association. With a multi-centered, rapid-recruitment protocol, weight and body size measurements were collected prior to diagnosis, and medical charts were reviewed for pathology results (n = 420 controls, 119 high-grade prostatic intraepithelial neoplasia (PIN) cases, and 286 cancer cases (41% Gleason > 6). In multivariable logistic regression models adjusting for age, PSA levels and history, DRE results, and number of cores at biopsy, the association between BMI and cancer was restricted to men with a smaller prostate volume (volume < 40 cm(3): OR(BMI > or = 30) = 2.17 (1.09, 4.32), p (trend) = 0.02; volume > or = 40 cm(3): OR(BMI > or = 30) = 0.77 (0.34, 1.77), p (trend) = 0.17; p (interaction) = 0.03). Similarly, the WHR and PIN association was significantly modified by prostate volume (volume < 40 cm(3): OR((WHR: Tertile 3 vs. T1)) = 3.76 (1.54, 9.21) (p (trend) < 0.01); volume > or = 40 m(3): OR((WHR: T3 vs. T1)) = 0.63 (0.32, 1.23) (p (trend) = 0.17); p (interaction) < 0.01). In conclusion, prostate volume acts as a modifier, and BMI and WHR are significantly associated with prostate cancer or PIN, respectively, in the absence of biopsy sampling error derived from obesity-related prostate enlargement. PMID- 17334812 TI - Psychological attitudes and risk of breast cancer in Japan: a prospective study. AB - OBJECTIVE: To examine the association between psychological factors and the risk of breast cancer prospectively in a non-Western population. METHODS: Data from the Japan Collaborative Cohort (JACC) study were analyzed. From 1988 to 1990, 34,497 women aged 40-79 years completed a questionnaire on medical, lifestyle and psychosocial factors. The rate ratios (RRs) of their responses were computed by fitting to proportional hazards models. RESULTS: During the mean follow-up period of 7.5 years, 149 breast cancer cases were documented. Those individuals who possessed "ikigai" (Japanese term meaning something that made one's life worth living) showed a significantly lower risk of breast cancer (multivariate-adjusted RR=0.66; 95% confidence interval [CI]=0.47-0.94). Those who perceived themselves as able to make decisions quickly also had a lower risk of breast cancer (multivariate-adjusted RR=0.56; 95% CI=0.36-0.87). The other factors investigated, including ease of anger arousal and self-perceived stress of daily life were not associated with breast cancer risk. CONCLUSIONS: Although further studies will be necessary to verify these findings, our results suggest that having "ikigai" and being decisive decrease an individual's subsequent risk of breast cancer. PMID- 17334814 TI - Toxicological evaluation of genetically modified cotton (Bollgard) and Dipel WP on the non-target soil mite Scheloribates praeincisus (Acari: Oribatida). AB - Insecticides derived from the bacterium Bacillus thuringiensis (Bt) and plants genetically modified (GM) to express B. thuringiensis toxins are important alternatives for insect pest control worldwide. Risk assessment of B. thuringiensis toxins to non-target organisms has been extensively studied but few toxicological tests have considered soil invertebrates. Oribatid mites are one of the most diverse and abundant arthropod groups in the upper layers of soil and litter in natural and agricultural systems. These mites are exposed to the toxic compounds of GM crops or pesticides mainly when they feed on vegetal products incorporated in the soil. Although some effects of B. thuringiensis products on Acari have been reported, effects on oribatid mites are still unknown. This study investigated the effects of the ingestion of Bt cotton Bollgard and of the B. thuringiensis commercial product Dipel WP on the pantropical species Scheloribates praeincisus (Scheloribatidae). Ingestion of Bollgard and Dipel did not affect adult and immature survivorship and food consumption (estimated by number of fecal pellets produced daily) or developmental time of immature stages of S. praeincisus. These results indicate the safety of Bollgard and Dipel to S. praeincisus under field conditions where exposition is lower and other food sources besides leaves of Bt plants are available. The method for toxicological tests described here can be adapted to other species of Oribatida, consisting on a new option to risk assessment studies. PMID- 17334815 TI - Predicting the population dynamics of the house dust mite Dermatophagoides pteronyssinus (Acari: Pyroglyphidae) in response to a constant hygrothermal environment using a model of the mite life cycle. AB - A generalised model of the life cycle of a house dust mite, which can be tailored to any particular species of domestic mite, is presented. The model takes into account the effects of hygrothermal conditions on each life cycle phase. It is used in a computer simulation program, called POPMITE, which, by incorporating a population age structure, is able to predict population dynamics. The POPMITE simulation is adapted to the Dermatophagoides pteronyssinus (Acari: Pyroglyphidae) (DP) mite using published data on the egg development period, total development period, adult longevity, mortality during egg development, mortality during juvenile development, and fecundity of individual DP mites held at a range of constant hygrothermal conditions. An example is given which illustrates how the model functions under constant hygrothermal conditions. A preliminary validation of POPMITE is made by a comparison of the POPMITE predictions with published measurements of population growth of DP mites held at a range constant hygrothermal conditions for 21 days. The POPMITE simulation is used to provide predictions of population growth or decline for a wide range of constant relative humidity and temperature combinations for 30 and 60 days. The adaptation of the model to correctly take account of fluctuating hygrothermal conditions is discussed. PMID- 17334816 TI - Life tables of the predatory mite Phytoseiulus longipes feeding on Tetranychus evansi at four temperatures (Acari: Phytoseiidae, Tetranychidae). AB - The tomato red spider mite, Tetranychus evansi, is reported as a severe pest of tomato and other solanaceous crops from Africa, from Atlantic and Mediterranean Islands, and more recently from the south of Europe (Portugal, Spain and France). A population of the predaceous mite Phytoseiulus longipes has been recently found in Brazil in association with T. evansi. The objective of this paper was to assess the development and reproduction abilities of this strain on T. evansi under laboratory conditions at four temperatures: 15, 20, 25 and 30 degrees C. The duration of the immature phase ranged from 3.1 to 15.4 days, at 30 and 15 degrees C, respectively. Global immature lower thermal threshold was 12.0 degrees C. Immature survival was high at all temperatures tested (minimum of 88% at 30 degrees C). The intrinsic rate of increase (r (m)) of P. longipes ranged from 0.091 to 0.416 female/female/day, at 15 and 30 degrees C, respectively. P. longipes would be able to develop at a wide range of temperatures feeding on T. evansi and has the potential to control T. evansi populations. PMID- 17334813 TI - Species distribution and antifungal susceptibility patterns of Candida spp. bloodstream isolates from a Brazilian tertiary care hospital. AB - In this work, we collect data from surveys of bloodstream Candida isolates performed in Brazil from 1996 to 2004. Besides, we analyzed the species distribution of bloodstream Candida isolates together with potential risk factors for candidemia and the susceptibility profile of these isolates in patients from Hospital das Clinicas in Goiania city, Brazil. Blood samples were collected in the admission day and on every 7 days, in the intensive care unit (ICU) of a tertiary hospital. Candida isolates were identified by standard protocols that included germ tube formation, chlamydoconidia production on cornmeal agar and sugar fermentation and assimilation tests. Data of patients were recorded and analyzed according to age at the time of diagnosis, gender and presence of potential risk factors. Statistical analysis was used to determine if the time of hospital permanence increased Candida colonization in ICU patients' blood. The antifungal susceptibility testing was performed by broth microdilution method according to document NCCLS/CLSI M27-A2. Among the 345 blood samples cultured, candidemia was recovered in 33 patients, which were isolated 51.5% of Candida non albicans. Fungemia was associated with long-term hospitalization. Fluconazole, itraconzole, voriconazole and amphotericin B exhibited a potent activity against all isolates of Candida. Voriconazole MICs were much low for all isolates tested. This work confirms data of increase of Candida non-albicans species in bloodstream in ICU and shows that voriconazole in vitro activity was higher than those of itraconazole, fluconazole and amphotericin B. PMID- 17334817 TI - Application of artificial neural network model for the development of optimized complex medium for phenol degradation using Pseudomonas pictorum (NICM 2074). AB - Biodegradation of phenol using Pseudomonas pictorum (NICM 2074) a potential biodegradant of phenol was investigated for its degrading potential under different operating conditions. The neural network input parameter set consisted of the same set of four levels of maltose (0.025, 0.05, 0.075 g/l), phosphate (3, 12.5, 22 g/l), pH (7, 8, 9) and temperature (30 degrees C, 32 degrees C, 34 degrees C) on phenol degradation was investigated and a Artificial Neural Network (ANN) model was developed to predict the extent of degradation. The learning, recall and generalization characteristic of neural networks was studied using phenol degradation system data. The efficiency of the model generated by the ANN, was tested and compared with the results obtained from an established second order polynomial multiple regression analysis (MRA). Further, the two models (ANN and MRA) were used to predict the percentage of degradation of phenol for blind test data. Performance of both the models were validated in the cases of training and test data, ANN was recommended based on the following higher coefficient of determination R (2); lower standard error of residuals and lower mean absolute percentage deviation. PMID- 17334818 TI - Alterations in aortic elasticity in noncompaction cardiomyopathy. AB - BACKGROUND: Noncompaction cardiomyopathy (NCCM) is a recently recognized disorder frequently associated with systolic and diastolic heart failures. This study was designed to examine aortic stiffness in NCCM patients and to compare these results to age- and gender-matched controls. METHODS: A total of 20 patients with typical echocardiographic features of NCCM (age 38 +/- 16 years, eight males) were investigated. Their results were compared to 20 age- and gender-matched controls. All subjects underwent a complete two-dimensional transthoracic echocardiographic examination. Systolic (SD) and diastolic (DD) ascending aortic diameters were recorded in M-mode at a level of 3 cm above the aortic valve from a parasternal long-axis view. Aortic stiffness index (beta) was calculated as a characteristic of aortic elasticity, as ln(SBP/DBP)/[(SD - DD)/DD], where SBP and DBP are the systolic and diastolic blood pressures, respectively, and ln is the natural logarithm. RESULTS: The number of noncompacted segments in the NCCM patients was 4.6 +/- 2.0. NCCM patients had significantly increased left ventricular dimensions and reduced left ventricular ejection fraction. Compared to controls, aortic stiffness index (beta) was significantly increased in NCCM patients (8.3 +/- 5.2 vs. 3.5 +/- 1.1, p < 0.001). CONCLUSION: Increased aortic stiffness can be observed in patients with NCCM with moderate to severe heart failure. These alterations may be due to neurohormonal changes in heart failure. PMID- 17334819 TI - Behavioural risk factors in two generations of non-Western migrants: do trends converge towards the host population? AB - Migrant mortality does not conform to a single pattern of convergence towards prevalence rates in the host population. To understand better how migrant mortality develops, it is necessary to further investigate how the underlying behavioural determinants change following migration. We studied whether the prevalence of behavioural risk factors over two generations of Turkish and Moroccan migrants converge towards the prevalence rates in the Dutch population. From a random sample from the population register of Amsterdam, 291 Moroccan and 505 Turkish migrants, aged 15-30, participated in a structured interview that included questions on smoking, alcohol consumption, physical inactivity and weight/height. Data from the Dutch population were available from Statistics Netherlands. By calculating age-adjusted Odds Ratio's, prevalence rates among both generations were compared with prevalence rates in the host population for men and women separately. We found indications of convergence across generations towards the prevalence rates in the host population for smoking in Turkish men, for overweight in Turkish and Moroccan women and for physical inactivity in Turkish women. Alcohol consumption, however, remained low in all subgroups and did not converge towards the higher rates in the host population. In addition, we found a reversed trend among Turkish women regarding smoking: the second generation smoked significantly more, while the first generation did not differ from ethnic Dutch. In general, behavioural risk factors in two generations of non Western migrants in the Netherlands seem to converge towards the prevalence rates in the Dutch population. However, some subgroups and risk factors showed a different pattern. PMID- 17334820 TI - Measurement of urine pH for epidemiological studies on bladder cancer. AB - Methods for efficiently identifying subjects with constantly acidic pH in epidemiological and clinical studies have not been assessed. We recruited 30 volunteers to estimate the minimum number of urine pH measurements using pH strips needed to identify subjects with "constantly acidic urine pH". Spearman's correlation coefficients between urine pH measured with a pH meter and with the four pH strips ranged from 0.94 to 0.95 (p < 0.001 for all four strips). Overall agreement within +/-0.5 pH units between the four strips and the pH meter ranged from 62.2% to 74.4%. When using a spot urine sample from a single morning to classify participants with respect to their urine pH, 80% of individuals fell into the acidic urine pH (pH equal to or lower than 6.0) group. When we required subjects to have urine pH equal to or lower than 6.0 in six consecutive AM spot urine samples and seven spot PM urine samples, only 20% of participants fulfilled this criterion. Measuring urine pH twice a day (early in the morning and early in the evening) during four consecutive days classified individuals in the same way as two daily measurements for one week. A single pH measurement from a spot urine sample is not reliable to identify individuals with constantly acidic pH. Morning and evening urine pH measurements with pH strips during four consecutive days identify individuals with constantly acidic urine pH individuals as well as one week of measurements, and thus might be useful to identify subjects with constantly acidic urine pH in epidemiological and clinical studies. PMID- 17334822 TI - Risk factors for developing tuberculosis in remand prisons in St. Petersburg, Russia - a case-control study. AB - BACKGROUND: Detainees have a substantial risk to develop tuberculosis (TB) due to a higher incidence of TB in remand prison compared to the civil community. They develop TB during incarceration not only due to poor living conditions in remand prison, but also due to some factors affecting their life before imprisonment. Prevention measures against TB spread from penitentiary institutions to society include study of factors, which contribute to TB development. Current study aims at identification of important risk factors of TB development in remand prison in St. Petersburg, Russia. METHODS: A retrospective matched case-control study was performed from May 2002 to May 2003 in two remand prisons in St. Petersburg. One hundred and fourteen prisoners (57 cases, 57 controls) were interviewed by using standardised questionnaire. Logistic regression analysis was performed to identify risk factors. RESULTS: Six factors were significantly linked to the risk of developing TB: narcotic drug use (odds ratio (OR): 2.6, 95% confidence interval (CI): 1.0-6.9), low income (OR: 3.2, CI: 1.2-8.6), high ratio of prisoners per available bed (OR: 4.0, CI: 1.1-15.0), not having own bed clothes (OR: 13.0, CI: 2.7-61.6), and little time outdoors (OR: 3.3, CI: 1.3-8.5). However, good housing before imprisonment (OR: 4.2, CI: 1.1-15.7) was a separate risk factor for TB. CONCLUSIONS: Three of the risk factors (high number of prisoners per bed, not having own bed clothes, and little time outdoors) are certainly possible to approach by improvement of conditions in remand prisons. The remaining three factors (narcotic drug use, good housing before imprisonment, and low income) provide knowledge about study population, but cannot be intervened by prison's medical staff. PMID- 17334821 TI - Major decline of hepatitis C virus incidence rate over two decades in a cohort of drug users. AB - Injecting drug users (DU) are at high risk for hepatitis C virus (HCV) and HIV infections. To examine the prevalence and incidence of these infections over a 20 year period (1985-2005), the authors evaluated 1276 DU from the Amsterdam Cohort Studies who had been tested prospectively for HIV infection and retrospectively for HCV infection. To compare HCV and HIV incidences, a smooth trend was assumed for both curves over calendar time. Risk factors for HCV seroconversion were determined using Poisson regression. Among ever-injecting DU, the prevalence of HCV antibodies was 84.5% at study entry, and 30.9% were co-infected with HIV. Their yearly HCV incidence dropped from 27.5/100 person years (PY) in the 1980s to 2/100 PY in recent years. In multivariate analyses, ever-injecting DU who currently injected and borrowed needles were at increased risk of HCV seroconversion (incidence rate ratio 29.9, 95% CI 12.6, 70.9) compared to ever injecting DU who did not currently inject. The risk of HCV seroconversion decreased over calendar time. The HCV incidence in ever-injecting DU was on average 4.4 times the HIV incidence, a pattern seen over the entire study period. The simultaneous decline of both HCV and HIV incidence probably results from reduced risk behavior at the population level. PMID- 17334823 TI - Outliers in SAR and QSAR: is unusual binding mode a possible source of outliers? AB - A lead optimization is usually carried out by structure-activity relationship (SAR) and/or quantitative structure-activity relationship (QSAR) studies. One of the assumptions in SAR and QSAR studies is that similar analogs bind to the same binding site in a similar binding mode. One often observes that there are outliers, especially in QSAR. However, most QSAR studies are carried out focusing their attention to the development of QSAR and leave the outliers without much attention. We searched a number of ligand-bound X-ray crystal structures from the protein structure database to find evidences that could indicate a possible source of outliers in SAR or QSAR. Our results show that unusual binding mode could be a source of outliers. PMID- 17334824 TI - All-atom molecular dynamics simulations using orientational constraints from anisotropic NMR samples. AB - Orientational constraints obtained from solid state NMR experiments on anisotropic samples are used here in molecular dynamics (MD) simulations for determining the structure and dynamics of several different membrane-bound molecules. The new MD technique is based on the inclusion of orientation dependent pseudo-forces in the COSMOS-NMR force field. These forces drive molecular rotations and re-orientations in the simulation, such that the motional time-averages of the tensorial NMR properties approach the experimentally measured parameters. The orientational-constraint-driven MD simulations are universally applicable to all NMR interaction tensors, such as chemical shifts, dipolar couplings and quadrupolar interactions. The strategy does not depend on the initial choice of coordinates, and is in principle suitable for any flexible molecule. To test the method on three systems of increasing complexity, we used as constraints some deuterium quadrupolar couplings from the literature on pyrene, cholesterol and an antimicrobial peptide embedded in oriented lipid bilayers. The MD simulations were able to reproduce the NMR parameters within experimental error. The alignment of the three membrane-bound molecules and some aspects of their conformation were thus derived from the NMR data, in good agreement with previous analyses. Furthermore, the new approach yielded for the first time the distribution of segmental orientations with respect to the membrane and the order parameter tensors of all three systems. PMID- 17334825 TI - Strong coupling effects during X-pulse CPMG experiments recorded on heteronuclear ABX spin systems: artifacts and a simple solution. AB - Simulation and experiment have been used to establish that significant artifacts can be generated in X-pulse CPMG relaxation dispersion experiments recorded on heteronuclear ABX spin-systems, such as (13)C( i )-(13)C( j )-(1)H, where (13)C( i ) and (13)C( j ) are strongly coupled. A qualitative explanation of the origin of these artifacts is presented along with a simple method to significantly reduce them. An application to the measurement of (1)H CPMG relaxation dispersion profiles in an HIV-2 TAR RNA molecule where all ribose sugars are protonated at the 2' position, deuterated at all other sugar positions and (13)C labeled at all sugar carbons is presented to illustrate the problems that strong (13)C-(13)C coupling introduces and a simple solution is proposed. PMID- 17334826 TI - Pressure effects on the abiotic polymerization of glycine. AB - Polymerization experiments were performed using dry glycine under various pressures of 5-100 MPa at 150 degrees C for 1-32 days. The series of experiments was carried out under the assumption that the pore space of deep sediments was adequate for dehydration polymerization of pre-biotic molecules. The products show various colors ranging from dark brown to light yellow, depending on the pressure. Visible and infrared spectroscopy reveal that the coloring is the result of formation of melanoidins at lower pressures. High-performance liquid chromatography and mass spectrometry analyses of the products show that: (1) glycine in all the experimental runs oligomerizes from 2-mer to 10-mer; (2) the yields are dependent on pressure up to 25 MPa and decrease slightly thereafter; and (3) polymerization progressed for the first 8 days, while the amounts of oligomers remained constant for longer-duration runs of up to 32 days. These results suggest that pressure inhibits the decomposition of amino acids and encourages polymerization in the absence of a catalyst. Our results further imply that abiotic polymerization could have occurred during diagenesis in deep sediments rather than in oceans. PMID- 17334827 TI - A novel mutated acetolactate synthase gene conferring specific resistance to pyrimidinyl carboxy herbicides in rice. AB - Acetolactate synthase (ALS) is the first common enzyme in the biosynthetic pathway of branched-chain amino acids. Mutations of specific amino acids in ALS have been known to confer resistance to ALS-inhibiting herbicides such as sulfonylureas and pyrimidinyl carboxy (PC) herbicides. However, mutations conferring exclusive resistance to PC have not yet been reported to date. We selected PC resistant rice calli, which were derived from anther culture, using one of the PCs, bispyribac-sodium (BS), as a selection agent. Two lines of BS resistant plants carrying a novel mutation, the 95th Glycine to Alanine (G95A), in ALS were obtained. In vitro ALS activity assay indicated that the recombinant protein of G95A-mutated ALS (ALS-G95A) conferred highly specific resistance to PC herbicides. In order to determine if the ALS-G95A gene could be used as a selection marker for rice transformation, the ALS-G95A gene was connected to ubiquitin promoter and introduced into rice. PC resistant plants containing integrated ALS-G95A gene were obtained after selection with BS as a selection agent. In conclusion, novel G95A mutated ALS gene confers highly specific resistant to PC-herbicides and can be used as a selection marker. PMID- 17334828 TI - Questions remaining in sulfolipid biosynthesis: a historical perspective. AB - The plant sulfolipid sulfoquinovosyldiacylglycerol was discovered by A.A. Benson in the late 1950s. The increasing availability of radioisotope-containing biological substrates such as (35)S-sulfate provided the means to discover novel biological compounds and to sketch out their biosynthetic pathways. During this time the structure of sulfolipid with its 6-deoxy-6-sulfo-alpha-D: -glucose (sulfoquinovose) headgroup was determined. Immediately, the origin of this unusual biological sulfonic acid mystified the scientific community and several proposals for its biosynthesis were developed and tested. Strong supportive evidence for the nucleotide pathway of sulfolipid biosynthesis became available with the discovery of the bacterial and plant genes encoding the enzymes of sulfolipid biosynthesis during the 1990s. This latter work was based on the foundations laid by A.A. Benson and confirmed one initial hypothesis on sulfolipid biosynthesis. An abbreviated summary of the turning points in defining the mechanism for sulfolipid biosynthesis and remaining issues in sulfolipid biochemistry are provided. PMID- 17334829 TI - Item response theory methods can improve the measurement of physical function by combining the modified health assessment questionnaire and the SF-36 physical function scale. AB - OBJECTIVE: To compare the measurement properties of the Modified Health Assessment Questionnaire [MHAQ], the SF-36((R)) Health Survey 10 item Physical Functioning scale [PF10], and scores from an item response theory (IRT) based scale combining the two measures. STUDY DESIGN: Rheumatoid arthritis (RA) patients (n = 339) enrolled in a multi-center, randomized, double-blind, placebo controlled trial completed the MHAQ and the SF-36 pre- and post-treatment. Psychometric analyses used confirmatory factor analysis and IRT models. Analyses of variance were used to assess sensitivity to changes in disease severity (defined by the American College of Rheumatism (ACR)) using change scores in MHAQ, PF10, and IRT scales. Analyses of covariance were used to assess treatment responsiveness. RESULTS: For the entire score range, the 95% confidence interval around individual patient scores was smaller for the combined (total) IRT based scale than for other measures. The MHAQ and PF10 were about 70% and 50% as efficient as the total IRT score of physical functioning in discriminating among ACR groups, respectively. The MHAQ and PF10 were also less efficient than the total IRT score in discriminating among treatment groups. CONCLUSIONS: Combining scales from the two short forms yields a more powerful tool with greater sensitivity to treatment response. PMID- 17334830 TI - Generic and disease-specific health related quality of life of liver patients with various aetiologies: a survey. AB - Most studies on health related quality of life (HRQoL) of chronic liver patients were done in small clinical populations or restricted to one aetiology or disease stage. There is still a need for a study in a large liver patient population with various aetiologies and disease stages, approaching a population-based study. We evaluated the impact of liver disease aetiology on generic HRQoL, disease specific HRQoL and fatigue and we compared HRQoL and fatigue between aetiological groups and healthy Dutch controls. Members of the Dutch liver patient association completed the Liver Disease Symptom Index, Short Form-36, and Multidimensional Fatigue Index-20. We compared the HRQoL between patients with viral hepatitis, autoimmune hepatitis, cholestatic diseases, hemochromatosis and other liver diseases by linear, ordinal and logistic regression, corrected for disease stage and other significant factors. Viral hepatitis patients showed a worse mental health than other aetiological groups. Hemochromatosis patients demonstrated 17% more bodily pain than viral hepatitis patients and the strongest decrease in role emotional health with increasing age. Aetiological groups showed a worse generic HRQoL and more fatigue than controls. In conclusion, viral hepatitis and hemochromatosis patients have a more impaired HRQoL than patients of other liver disease aetiological groups. PMID- 17334831 TI - Psychometric properties of the initial Brazilian version of the CHQ-PF50 applied to the caregivers of children and adolescents with cerebral palsy. AB - GOALS: To evaluate the psychometric properties of the initial Brazilian version of the Child Health Questionnaire(CHQ-PF50) in children and adolescents with cerebral palsy(CP). METHODS: The caregivers of 5- to 18-year-old children and adolescents with CP answered the self-administered CHQ-PF50 questionnaire. Data quality, reliability and validity were studied. The Gross Motor Function Measure was used to assess physical function. RESULTS: Ninety-six caregivers answered the questionnaire. Patient age ranged from 5 to 17.9 years (mean: 9.3 years). Missing data rate was low. Floor effect occurred in 3 scales and was substantial for quadriplegia group (63.6-77.3%). Ceiling effect occurred in 9 scales. Reliability was adequate for all scales except for the general health perception scale (Cronbach alpha coefficient = 0.24). The validity was adequate in general, but the role/social limitations-emotional behavioral scale was not satisfactory for discriminant and divergent validity. CONCLUSION: The initial Brazilian version of the CHQ-PF50 showed, in general, adequate psychometric properties for application in patients with CP. Although floor and ceiling effects are expected in heterogeneous group as a limitation inherent to generic assessment instruments, they must be carefully considered in further studies. The general health perception and role/social limitations-emotional behavioral scale must be further reviewed for this population. PMID- 17334832 TI - Do hydronephrosis and extracorporeal shock wave lithotripsy affect carbohydrate antigens? AB - OBJECTIVES: To investigate carbohydrate antigen (CA 19-9, CA 15-3, and CA 125) levels in the patients who had hydronephrosis with renal stones and in whom Extracorporeal shock wave lithotripsy (ESWL) was performed. MATERIALS AND METHODS: This prospective study included 20 people with no known disease for control group and 30 patients who had hydronephrosis with renal stones and in whom ESWL was performed between January 2005 and January 2006. None of patients had urinary infection and malignancy. The blood for carbohydrate antigens was taken pre-ESWL and 30 min after ESWL in both groups. CA 19-9, CA 15-3, and CA 125 in the serum were tested with the electro-immunoassay method on the Roche E-170 apparatus with the original Roche kit. RESULTS: The CA 19-9 and CA 125 values in the patients group were found to be statistically significant when compared with the control group but the CA 15-3 was not found to be significant. However, CA 19 9, CA 15-3, and CA 125 values of post-ESWL were not statistically significant when compared with pre-ESWL group (P > 0.05). CONCLUSIONS: The average serum values of CA 125 and CA 19-9 in patients were found to be significantly high. However, serum values of CA 19-9, CA 15-3, and CA 125 were not affected by ESWL. PMID- 17334833 TI - p38 MAPK in regulating cellular responses to ultraviolet radiation. AB - Solar ultraviolet (UV) radiation is a major environmental factor that causes DNA damage, inflammation, erythema, sunburn, immunosuppression, photoaging, gene mutations, and skin cancer. p38 mitogen activated protein kinase (MAPK) are strongly activated by UV radiation, and play important roles in regulating cellular responses to UV. In this review, we examine the role played by p38 MAPK in mediating UV-induced cell cycle, apoptosis, inflammation, and skin tanning response. We review the role played by p38 MAPK in transcriptional regulation of key downstream genes that have been implicated in the regulation of cellular responses to UV radiation. Understanding this will undoubtedly help in the prevention and control of UV-induced damage and the development of novel therapeutic strategies. PMID- 17334835 TI - Role of sustained overexpression of central nervous system IGF-I in the age dependent decline of mouse excitation-contraction coupling. AB - We investigated the effects of exclusive and sustained transgenic overexpression of insulin-like growth factor (IGF)-I in the central nervous system (CNS) on the age-dependent decline in muscle strength, excitation-contraction coupling, muscle innervation and neuromuscular junction postterminal architecture. We found that (1) transgenic IGF-I overexpression in the CNS does not modify the decline in extensor digitorum longus (EDL) and soleus muscle weight with aging and (2) strength significantly decreases in transgenic (Tg) compared to wild-type mice. The latter finding is consistent with (3) the decreased absolute and specific force measured in the EDL muscle in vitro and (4) the decreased charge movement and peak intracellular Ca(2+) mobilization in individual muscle fibers from old IGF-I Tg mice compared to young wild-type mice, which also is associated with (5) decreased dihydropyridine receptor alpha(1)-subunit expression in old compared to young IGF-I Tg mice. (6) Tg IGF-I prevents a change in muscle fiber type that is associated with (7) improved muscle innervation and postterminal neuromuscular structure. (8) IGF-I is expressed extensively across the spinal cord gray matter and the lateral motor column. Our results raise questions about the timing and cell location of CNS IGF-I overexpression necessary to prevent or to ameliorate age-dependent alterations in the structure and function of skeletal muscle. PMID- 17334836 TI - On the role of pore helix in regulation of TRPV5 by extracellular protons. AB - The transient receptor potential channel TRPV5 is localized to the apical membrane of the distal renal tubule and plays an important role in the regulation of transepithelial Ca(2+) reabsorption in kidney. We have previously reported that extracellular protons inhibit TRPV5 by binding to glutamate-522 (E522) in the extracellular domain of the channel. We suggested that E522 is an extracellular "pH sensor" and its titration by extracellular protons inhibits TRPV5 via conformational change(s) of the pore helix. We now report that mutation of a pore helix residue glutamate-535 to glutamine (E535Q) enhances the sensitivity of the channel to inhibition by extracellular protons (i.e., shifting the apparent pKa for inhibition by extracellular protons to the more alkaline extracellular pH). The enhancement of extracellular proton-mediated inhibition of E535Q mutant is also dependent on E522. We have also reported that intracellular acidification enhances the sensitivity of TRPV5 to inhibition by extracellular protons. We now find that modulation of the extracellular proton-mediated inhibition by intracellular acidification is preserved in the E535Q mutant. These results provide further support for the idea that pore helix is involved in the regulation of TRPV5 by extracellular protons. Inhibition of TRPV5 by extracellular protons may contribute to hypercalciuria in diseases associated with high acid load. PMID- 17334837 TI - Selective cytochrome c displacement by phosphate and Ca(2+) in brain mitochondria. AB - In brain mitochondria, phosphate- and Ca(2+)-dependent cytocrome c (cyt c) release reveals pools that interact differently with the inner membrane. Detachment of the phosphate-dependent pool did not influence the pool released by Ca(2+). Cyt c pools were also detected in a system of cyt c reconstituted in cardiolipin (CL) liposomes. Gradual binding of cyt c (1 nmol) to CL/2-[12-(7 nitrobenz- 2-oxa-1,3-diazol-4-yl)amino]dodecanoyl-1-hexadecan oyl-sn-glycero-3 phosphocholine (NBDC(12)-HPC) liposomes (10 nmol) produced NBD fluorescence quenching up to 0.4 nmol of added protein. Additional bound cyt c did not produce quenching, suggesting that cyt c-CL interactions originate distinct cyt c pools. Cyt c was removed from CL/NBDC(12)-HPC liposomes by either phosphate or Ca(2+), but only Ca(2+) produced fluorescence dequenching and leakage of encapsulated 8 aminonaphthalene-1,3,6-trisulfonic acid/p-xylene-bis-pyridinium bromide. In mitochondria, complex IV activity and mitochondrial membrane potential (Deltapsi(m)) were not affected by the release of the phosphate-dependent cyt c pool. Conversely, removal of cyt c by Ca(2+) caused inhibition of complex IV activity and impairment of Deltapsi(m). In a reconstituted system of mitochondria, nuclei and supernatant, cyt c detached from the inner membrane was released outside mitochondria and triggered events leading to DNA fragmentation. These events were prevented by enriching mitochondria with exogenous CL or by sequestering released cyt c with anti-cyt c antibody. PMID- 17334838 TI - Overexpression of Na(+)/K (+)-ATPase parallels the increase in sodium transport and potassium recycling in an in vitro model of proximal tubule cellular ageing. AB - Na(+)/K(+)-ATPase plays a key role in the transport of Na(+) throughout the nephron, but ageing appears to be accompanied by changes in the regulation and localization of the pump. In the present study, we examined the effect of in vitro cell ageing on the transport of Na(+) and K(+) ions in opossum kidney (OK) cells in culture. Cells were aged by repeated passing, and Na(+)/K(+)-ATPase activity and K(+) conductance were evaluated using electrophysiological methods. Na(+)K(+)-ATPase alpha(1)- and beta(1)-subunit expression was quantified by Western blot techniques. Na(+)/H(+) exchanger activity, changes in membrane potential, cell viability, hydrogen peroxide production and cellular proliferation were determined using fluorimetric assays. In vitro cell ageing is accompanied by an increase in transepithelial Na(+) transport, which results from an increase in the number of Na(+)/K(+)-ATPase alpha(1)- and beta(1)-subunits, in the membrane. Increases in Na(+)/K(+)-ATPase activity were accompanied by increases in K(+) conductance as a result of functional coupling between Na(+)/K(+)-ATPase and basolateral K(+) channels. Cell depolarization induced by both KCl and ouabain was more pronounced in aged cells. No changes in Na(+)/H(+) exchanger activity were observed. H(2)O(2) production was increased in aged cells, but exposure for 5 days to 1 and 10 microM: of H(2)O(2) had no effect on Na(+)/K(+)-ATPase expression. Ouabain (100 nM: ) increased alpha(1)-subunit, but not beta(1)-subunit, Na(+)/K(+)-ATPase expression in aged cells only. These cells constitute an interesting model for the study of renal epithelial cell ageing. PMID- 17334839 TI - Mutations stabilize small subunit ribosomal RNA in desiccation-tolerant cyanobacteria nostoc. AB - The ribosomal RNA molecule is an ideal model for evaluating the stability of a gene product under desiccation stress. We isolated 8 Nostoc strains that had the capacity to withstand desiccation in habitats and sequenced their 16S rRNA genes. The stabilities of 16S rRNAs secondary structures, indicated by free energy change of folding, were compared among Nostoc and other related species. The results suggested that 16S rRNA secondary structures of the desiccation-tolerant Nostoc strains were more stable than that of planktonic Nostocaceae species. The stabilizing mutations were divided into two categories: (1) those causing GC to replace other types of base pairs in stems and (2) those causing extension of stems. By mapping stabilizing mutations onto the Nostoc phylogenetic tree based on 16S rRNA gene, it was shown that most of stabilizing mutations had evolved during adaptive radiation among Nostoc spp. The evolution of 16S rRNA along the Nostoc lineage is suggested to be selectively advantageous under desiccation stress. PMID- 17334841 TI - Genetic and comparative transcriptome analysis of bromodomain factor 1 in the salt stress response of Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae BDF1 gene, which encodes a bromodomain-containing transcription factor, was previously isolated by transposon mutugenesis in a screen for salt-sensitive mutants. However, the salt stress response mechanism regulated by bromodomain transcription factor 1 protein (Bdf1p) remains poorly understood. In this report, genetic analysis indicated that the salt sensitivity of the BDF1 deletion mutant was suppressed by increased gene dosage of its homologous gene BDF2. Furthermore, comparative transcriptome analysis revealed that the differences in transcriptional response between the wild type and the bdf1Delta mutant in the presence of salt stress (0.6 mol/L NaCl, 45 min) were mainly related to cell-wall biosynthesis, the mitochondria, and several unknown genes. Our results provided further information about the regulatory mechanism involved in the salt stress response and adds new insight for understanding the biological functional of bromdomain-containing proteins in cellular processes. PMID- 17334840 TI - Cloning of a laccase gene from a novel basidiomycete Trametes sp. 420 and its heterologous expression in Pichia pastoris. AB - The laccase gene lacD, cloned from a novel laccase-producing basidiomycete Trametes sp. 420, contained 2,052 base pairs (bp) interrupted by 8 introns. lacD displayed a relatively high homology with laccase genes from other white rot fungi, whereas the homology between lacD and laccase genes from plants, insects, or bacteria was less than 25%. A 498-amino acid peptide encoded by the lacD cDNA was heterologously expressed in the Pichia pastoris strain GS115, resulting in the highest yield of laccase (8.3 x 10(4) U/l) as determined with ABTS (2,2' azinobis [3-ethylbenzothia-zoline-6-sulfonic acid]) as the substrate. Additionally, the enzyme activity of recombinant laccase on decolorization of some industrial dyes was assessed. PMID- 17334842 TI - Characterization of a phenazine-producing strain Pseudomonas chlororaphis GP72 with broad-spectrum antifungal activity from green pepper rhizosphere. AB - A new Pseudomonas strain, designated GP72, was isolated from green pepper rhizosphere and identified as a member of species Pseudomonas chlororaphis based on morphology; conventional biochemical and physiologic tests; Biolog GN system (Biolog Inc., Hayward, CA); and 16S rDNA sequence analysis. The secondary metabolites produced by this strain have shown broad-spectrum antifungal activity against various phytopathogens of agricultural importance in vitro. Two main antifungal substances produced by this strain proved to be phenazine-1-carboxylic acid and 2-hydroxyphenazine with further purification and structure elucidation based on ultraviolet-absorbent spectrum scanning, atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) spectrum, and (1)H,(13)C nuclear magnetic resonance spectrums. Strain GP72 could produce quorum-sensing signaling molecules of N-butanoyl-L-homoserine lactone and N-hexanoyl-L-homoserine lactone, which were found to accumulate with different quantities in King's medium B and pigment producing medium, respectively. PMID- 17334843 TI - Cloning and identification of a gene encoding spore cortex-lytic enzyme in Bacillus thuringiensis. AB - Spore cortex-lytic enzymes are essential for germination in Bacilli. A gene encoding spore cortex-lytic enzyme designated sleB was cloned from Bacillus thuringiensis. Disruption of sleB did not affect vegetative growth of B. thuringiensis, but the fall in optical density at 600 nm in the mutant spores was much slower than in the wild type strain during spore germination induced by L alanine. Moreover, the mutant spores did not become completely dark, as compared with the wild type strain. These showed that sleB is required for normal spore germination in B. thuringiensis. Reverse transcription polymerase chain reaction analysis indicated that sleB is transcribed during sporulation. Western blot experiment also proved that SleB accumulated in sporulating cells as a precursor protein, and in spores as a mature processed form. PMID- 17334844 TI - Verification and rapid identification of soybean rhizobia in Indian soils. AB - Sixty root nodule isolates of soybean rhizobia indigenous to eight field sites in India were characterized using PCR-RFLP for repeated sequence RSalpha a 1195-bp DNA fragment, indole acetic acid production, and nitrogenase activity. Site dependent variations were observed in terms of IAA production and nitrogenase activities. RSalpha was conserved in slow-growing soybean rhizobia across locations and sites and was absent in other Rhizobiaceae members and other bacterial genera. The results suggest that RSalpha can be a useful molecular marker for slow-growing soybean rhizobia. The study also showed the low presence of soybean nodulating fast growers in Indian soils. PMID- 17334845 TI - Purification and partial characterization of an antimicrobial peptide produced by a novel Bacillus sp. isolated from the Amazon Basin. AB - An antimicrobial peptide produced by a new Bacillus species isolated from the Amazon Basin was purified and characterized. The antimicrobial peptide was purified by ammonium sulfate precipitation, gel filtration, and ion exchange chromatography, and after the final purification step, one active fraction was obtained, designated BLS P34. Direct activity on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was observed. A single band on SDS PAGE suggested that the peptide was purified to homogeneity and had a molecular mass of about 5 kDa. The molecular weight (MW) was accurately determined by mass spectroscopy as 1456 Da. The purified BLS P34 remained active over a wide temperature range and was susceptible to all proteases tested. PMID- 17334846 TI - Cloning and characterization of a novel crystal protein from a native Bacillus thuringiensis isolate highly active against Aedes aegypti. AB - We characterized a novel Bacillus thuringiensis isolate native to Argentina (FCC 41) that exhibits a mosquitocidal activity higher than the reference B. thuringiensis subsp. israelensis. This isolate shows a rounded crystal harboring two major proteins of about 70-80 kDa. Moreover, we cloned and sequenced the encoding gene of one of the crystal proteins (Cry) consisting of an open reading frame of 2061 pb that encodes a protein of 687 amino acid residues. The deduced amino acid sequence has a predicted relative molecular mass of 78 kDa and is 52% and 45% identical to those of the reported Cry24Aa and Cry24Ba sequences, respectively. The novel Cry protein was designated as Cry24Ca, which also exhibited larvicidal activity against Aedes aegypti when its encoding gene was expressed in an Escherichia coli host strain. PMID- 17334847 TI - Characterization of a beta-glucosidase produced by a high-specific growth-rate mutant of Cellulomonas flavigena. AB - The mutant strain PN-120 of Cellulomonas flavigena produces a ss-glucosidase that is 10-fold more active than the corresponding enzyme isolated from the parental strain. These enzymes were partially purified through Q Sepharose and Bio-Gel filtration. A single protein band was detected on polyacrylamide-gel electrophoresis/zymogram using 4-methylumbelliferyl-beta-D-glucoside. On sodium dodecyl sulfate-PAGE, the enzyme displayed three protein bands, suggesting that in C. flavigena the enzyme is oligomeric with a molecular mass of 210 kDa. On purification, the specific activity of ss-glucosidase isolated from PN-120 was increased 16-fold and showed three times more affinity for cellobiose than the enzyme of the parental strain; nevertheless, the optimum pH and temperature were similar for both enzymes. The kinetic parameters suggested that the increase in the activity of the enzyme, from the mutant strain, was caused by a mutation that affects the catalytic site of the enzyme. The partial amino-acid sequence of the isolated enzyme confirmed that it is a beta-glucosidase because of its homology with other beta-glucosidases produced by cellulolytic bacteria and fungi. PMID- 17334848 TI - Embolization of a hemorrhoid following 18 hours of life-threatening bleeding. AB - Hemorrhoids usually do not pose diagnostic difficulties and they rarely cause massive bleeding. We report a case of massive rectal bleeding over 18 h needing 22 U blood transfusion treated by superselective transcatheter coil embolization 12 h following operative treatment performed in a different hospital. Diagnostic angiography with a view to superselective embolization, following failure of sigmoidoscopy to localize and treat the cause of hemorrhage, might act as a life saving treatment in massive rectal bleeding, obviating the need for repeated endoscopy or emergency surgery. PMID- 17334849 TI - Robust postmortem survival of murine vestibular and cochlear stem cells. AB - Potential treatment strategies of neurodegenerative and other diseases with stem cells derived from nonembryonic tissues are much less subjected to ethical criticism than embryonic stem cell-based approaches. Here we report the isolation of inner ear stem cells, which may be useful in cell replacement therapies for hearing loss, after protracted postmortem intervals. We found that neonatal murine inner ear tissues, including vestibular and cochlear sensory epithelia, display remarkably robust cellular survival, even 10 days postmortem. Similarly, isolation of sphere-forming stem cells was possible up to 10 days postmortem. We detected no difference in the proliferation and differentiation potential between stem cells isolated directly after death and up to 5 days postmortem. At longer postmortem intervals, we observed that the potency of sphere-derived cells to spontaneously differentiate into mature cell types diminishes prior to the cells losing their potential for self-renewal. Three-week-old mice also displayed sphere-forming stem cells in all inner ear tissues investigated up to 5 days postmortem. In summary, our results demonstrate that postmortem murine inner ear tissue is suited for isolation of stem cells. PMID- 17334850 TI - Identification of ClC-2 and CIC-K2 chloride channels in cultured rat type IV spiral ligament fibrocytes. AB - Voltage-gated chloride channels (ClCs) are important mediators of cellular ion homeostasis and volume regulation. In an earlier study, we used immunohistochemical, Western blot, and reverse transcriptase PCR (RT-PCR) approaches to identify ClC-K variants in types II, IV, and V fibrocytes of the rodent spiral ligament. We have now confirmed the expression of ClC-K2 in these cells by in situ hybridization. All three of these fibrocyte subtypes are thought to be involved in cochlear K(+) recycling; thus, it is important to understand the precise mechanisms regulating their membrane conductance and the role played by ClCs in this process. In this study, we report the characterization of a secondary cell line derived from explants from the region of the rat spiral ligament underlying and inferior to the spiral prominence. The cultured cells were immunopositive for vimentin, Na,K/ATPase, Na,K,Cl-cotransporter, carbonic anhydrase isozyme II, and creatine kinase isozyme BB, but not for cytokeratins or Ca/ATPase, an immunostaining profile indicative of the type IV subtype. Evaluation of the cultures by RT-PCR and Western blot analysis confirmed the presence of both ClC-2 and -K2. Whole-cell patch clamp recordings identified two biophysically distinct Cl(-) currents in the cultured cells. One, an inwardly rectifying Cl(-) current activated by hyperpolarization or decreasing extracellular pH corresponded with the properties of ClC-2. The other, a weak outwardly rectifying Cl(-) current regulated by extracellular pH, Cl(-), and Ca(2+) resembled the channel characteristics of ClC-K2 when expressed in Xenopus oocytes. These findings suggest that at least two functionally different chloride channels are involved in regulating membrane anion conductance in cultured type IV spiral ligament fibrocytes. PMID- 17334851 TI - Analysis of early postoperative morbidity among patients with rectal cancer treated with and without neoadjuvant chemoradiotherapy. AB - BACKGROUND: The impact of neoadjuvant treatment and their subsequent early complications in the treatment of rectal cancer has not been adequately assessed. The aim of this prospective study was to evaluate early postoperative morbidity and mortality among patients with rectal cancer treated with adjuvant radiotherapy and chemotherapy followed by surgery, compared with patients treated with surgery alone. We also identified independent risk factors associated with early major complications. METHODS: Between 1995 and 2004, 273 consecutive patients underwent treatment for rectal cancer. A total of 170 patients (group A) received preoperative radiotherapy with a total of 45-50.4 Gy (180 cGy per day) and 5-fluorouracil-based chemotherapy, followed by surgery; 103 patients (group B) were treated with surgery alone. Dependent variables related to patients, treatment, radiotherapy, and tumor were analyzed. RESULTS: Both groups were similar with regard to age, sex, body mass index, American Society of Anesthesiologists (ASA) score, and tumor location but not for ileostomy (27% in group A vs. 6.8% in group B). The number of complications was similar in both groups (43.1% in group A vs. 44.6% in group B). No differences in wound infection (8.2% vs. 7.8%), intra-abdominal abscess (4.7% vs. 4.9%), anastomotic dehiscence (4.2% vs. 3.8%), postoperative hemorrhage (3.5% vs. 3.9%), urinary complications (6.5% vs. 4.9%), paralytic ileus (8.9% vs. 9.7%), or general complications (7.1% vs. 9.6%) were found. The global mortality in the first 30 days after surgery was .7%. An ASA score of III-IV and surgery duration longer than 3 hours were identified as independent prognostic factors for early complications. CONCLUSIONS: Preoperative chemoradiation in patients with rectal cancer treated with surgery is not associated with a higher incidence of early postoperative complications. The patient's preoperative clinical condition and lengthy surgery time are prognostic factors for early complications. PMID- 17334852 TI - A small animal positron emission tomography study of the effect of chemotherapy and hormonal therapy on the uptake of 2-deoxy-2-[F-18]fluoro-D-glucose in murine models of breast cancer. AB - PURPOSE: We used small animal positron emission tomography (PET) imaging to monitor the time-course of tumor metabolic response to hormone and chemotherapy in a murine model of hormone-sensitive breast cancer. PROCEDURES: Estrogen receptor positive murine mammary carcinomas were inoculated in Balb/c mice. Small animal PET imaging using 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) was used to assess tumor metabolic activity. Imaging was done before and at days 1, 7, and 14 after the administration of doxorubicin, methotrexate, letrozole, or placebo. The tumor uptake of FDG was calculated from a region-of-interest drawn around the tumor. RESULTS: All treatments resulted in a decrease in tumor growth rate and end volume compared to untreated control. FDG uptake was also markedly decreased after treatment although a flare reaction was observed on PET at day 7, the intensity of which varied according to the treatment modality. CONCLUSION: PET imaging is sensitive to detect early changes associated with therapy in murine breast cancer models. A flare reaction was observed 7 days after the initiation of therapy. PMID- 17334853 TI - Understanding the placebo effect: contributions from neuroimaging. AB - Neuroimaging studies have provided a major contribution to our understanding of the mechanisms of the placebo effect in neurological and psychiatric disorders. Expectation of symptom improvement has long been believed to play a critical role in the placebo effect, and is associated with increased endogenous striatal dopamine release in Parkinson's disease and increased endogenous opioid transmission in placebo analgesia. Evidence from positron emission tomography and functional magnetic resonance imaging studies suggests that expectations of symptom improvement are driven by frontal cortical areas, particularly the dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortices. The ventral striatum is involved in the expectation of rewarding stimuli and, together with the prefrontal cortex, has also been shown to play an important role in the placebo-induced expectation of therapeutic benefit. Understanding the mechanisms of the placebo effect has important implications for treatment of several medical conditions, including depression, pain, and Parkinson's disease. PMID- 17334854 TI - Functional imaging of cerebral blood flow and glucose metabolism in Parkinson's disease and Huntington's disease. AB - Brain imaging of cerebral blood flow and glucose metabolism has been playing key roles in describing pathophysiology of Parkinson's disease (PD) and Huntington's disease (HD), respectively. Many biomarkers have been developed in recent years to investigate the abnormality in molecular substrate, track the time course of disease progression, and evaluate the efficacy of novel experimental therapeutics. A growing body of literature has emerged on neurobiology of these two movement disorders in resting states and in response to brain activation tasks. In this paper, we review the latest applications of these approaches in patients and normal volunteers at rest conditions. The discussions focus on brain mapping studies with univariate and multivariate statistical analyses on a voxel basis. In particular, we present data to validate the reproducibility and reliability of unique spatial covariance patterns related with PD and HD. PMID- 17334855 TI - A molecular comparison of plumage and soil bacteria across biogeographic, ecological, and taxonomic scales. AB - We used molecular methods to determine the microbial community of soil and avian plumage across biogeographic, ecological, and taxonomic scales. A total of 17 soil and 116 feather samples were collected from five avian species across multiple habitat types within one Neotropical and one temperate locality. Hypotheses regarding patterns of microbial composition relative to acquisition and dispersal of plumage bacteria in the ecosystem were tested by comparing microbial communities within and between soil and plumage. Samples from the plumage of American Redstarts (Setophaga ruticilla) were collected across both habitat types and geographic scales for intraspecific comparisons. The microbial diversity in avian plumage was moderately diverse and was dominated by Pseudomonas species. Despite a highly significant individual bird effect on microbial composition of the plumage, we detected significant biogeographic and type of habitat effects. Pseudomonas species were more abundant on the temperate site when all avian species were included in the analysis, and Bacillus subtilis and Xanthomonas groups were more abundant on the Neotropical site for redstarts alone. However, 16S rDNA sequence libraries were not significantly different between Jamaican and Maryland redstarts. Biogeographic and habitat effects were significant and more pronounced for soil samples indicating lower dispersal of soil microbiota. We detected a significant difference between soil and plumage microbial communities suggesting that soil plays a small role in plumage bacterial acquisition. Our results suggest bacterial communities on the plumage of birds are dynamic and may change at different stages in a bird's annual cycle. PMID- 17334856 TI - Diversity of cultivated and uncultivated actinobacterial endophytes in the stems and roots of rice. AB - A dual approach consisting of cultivation and molecular retrieval of actinobacterial 16S rRNA genes was used to characterize the diversity of actinobacterial community inhabiting interior of rice stems and roots. Streptomyces is the most frequently isolated genus from rice stems and roots. Forty-five clones chosen randomly among 250 clones in the 16S rRNA gene clone library from roots were affiliated with nine genera of actinobacteria and uncultured actinobacteria (Mycobacterium, Streptomyces, Micromonospora, Actinoplanes, Frankia, Dactylosporangium, Amycolatopsis, Corynebacterium, Rhodococcus, and uncultured actinobacterium). However, 33 clones from stems were affiliated with four genera and uncultured actinobacteria (Streptomyces, Mycobacterium, Nocardiodies, Janibacter, uncultured earthworm cast bacterium, uncultured earthworm intestine bacterium, and uncultured actinobacterium). Species similar to S. cyaneus were isolated from surface-sterilized roots and stems of rice and detected inside rice roots by culture-independent methods. Species similar to S. caviscabies, S. scabies, and S. turgidiscabies were simultaneously detected from the interior of rice stems by the culture-dependent and culture-independent methods. S. galilaeus was detected from the interior of rice stems and roots. These results indicated that some actinobacterial populations in rice stems were correlated with those in roots. PMID- 17334857 TI - Single-cell Raman spectral profiles of Pseudomonas fluorescens SBW25 reflects in vitro and in planta metabolic history. AB - Single-cell Raman microspectroscopy has the potential to report on the whole-cell chemical composition of bacteria, reflecting metabolic status as well as growth history. This potential has been demonstrated through the discriminant functional analysis of Raman spectral profiles (RSP) obtained from the soil and plant associated bacterium Pseudomonas fluorescens SBW25, grown in vitro using defined media, and in planta using 3-month-old sugar beets (Beta vulgaris var. Roberta). SBW25 in vitro RSP data showed significant variation between those cells grown on different amino acids, sugars, TCA cycle intermediates, rich King's B, and culture media derived from the sugar beet phytosphere. Raman analysis was also able to follow the transition of SBW25 starved of carbon over a period of days, and SBW25 in planta RSP data also showed variation with significant differences between bacteria recovered from soil and the rhizosphere. SBW25 whole-cell chemical composition, and therefore growth and metabolic history, could be interpreted by coanalyzing in vitro and in planta RSP data. SBW25 recovered from the phytosphere was found to be more similar to SBW25 grown in vitro on Fru or Asp, rather than on Glc or Arg, and quite dissimilar to that resulting from carbon starvation. This suggests that SBW25 growth in the phytosphere is generally neither carbon-catabolite-repressed nor carbon-limited. These findings demonstrate that the analysis of single-cell RSP can differentiate between isogenic populations of bacteria with different metabolic histories or after recovery from different parts of their natural environment. In addition, Raman analysis is also capable of providing biologically relevant biochemical inferences, which might then be tested to uncover the mechanistic basis (biochemical-metabolic-genetic) differentiating bacteria growing in complex environments and exposed to different conditions. PMID- 17334859 TI - Fungi on leaf blades of Phragmites australis in a brackish tidal marsh: diversity, succession, and leaf decomposition. AB - Although fungi are known to colonize and decompose plant tissues in various environments, there is scanty information on fungal communities on wetland plants, their relation to microhabitat conditions, and their link to plant litter decomposition. We examined fungal diversity and succession on Phragmites australis leaves both attached to standing shoots and decaying in the litter layer of a brackish tidal marsh. Additionally, we followed changes in fungal biomass (ergosterol), leaf nitrogen dynamics, and litter mass loss on the sediment surface of the marsh. Thirty-five fungal taxa were recorded by direct observation of sporulation structures. Detrended correspondence analysis and cluster analysis revealed distinct communities of fungi sporulating in the three microhabitats examined (middle canopy, top canopy, and litter layer), and indicator species analysis identified a total of seven taxa characteristic of the identified subcommunities. High fungal biomass developed in decaying leaf blades attached to standing shoots, with a maximum ergosterol concentration of 548 +/- 83 microg g(-1) ash-free dry mass (AFDM; mean +/- SD). When dead leaves were incorporated in the litter layer on the marsh surface, fungi experienced a sharp decline in biomass (to 191 +/- 60 microg ergosterol g(-1) AFDM) and in the number of sporulation structures. Following a lag phase, species not previously detected began to sporulate. Leaves placed in litter bags on the sediment surface lost 50% of their initial AFDM within 7 months (k = -0.0035 day(-1)) and only 21% of the original AFDM was left after 11 months. Fungal biomass accounted for up to 34 +/- 7% of the total N in dead leaf blades on standing shoots, but to only 10 +/- 4% in the litter layer. These data suggest that fungi are instrumental in N retention and leaf mass loss during leaf senescence and early aerial decay. However, during decomposition on the marsh surface, the importance of living fungal mass appears to diminish, particularly in N retention, although a significant fraction of total detrital N may remain associated with dead hyphae. PMID- 17334860 TI - Patient-reported outcomes. How important are they? AB - Outcome after surgical treatment has been based predominantly on objective criteria (biomedical model) and has largely ignored, until recently, the expectations, personal feelings, satisfaction, and quality of life of patients (outcomes model). The importance of this derives from considerations that the viewpoints and priorities of patients may not be the same as those of their surgeons. Furthermore, there is often little correlation between symptom severity and disease severity. Measures of quality of life and patient satisfaction are, thus, important in valid assessment of the results of surgical treatment. Global assessment based on both the biomedical and outcomes models constitutes the ideal. Questionnaires designed to measure both quality life (generic and specific) and patient satisfaction with treatment require careful development and validation by appropriate studies. PMID- 17334861 TI - Complications after a 5-year experience with laparoscopic donor nephrectomy: the Indiana University experience. AB - BACKGROUND: Laparoscopic donor nephrectomy (LDN) is becoming the standard of care for living donor nephrectomy. However, questions have been raised about the safety of LDN for the donor and about the potentially increased rates for ureteral complications experienced by the recipient. In this report, the authors review their 5-year experience with 253 living laparoscopic donor nephrectomies. METHODS: A retrospective chart review was performed for 253 laparoscopic live donors. Graft function and survival were compared using recipient postoperative creatinine values up to 12 months. RESULTS: The overall rate of complications in the investigated series was 10.3%. There were seven intraoperative complications (2.8%), three of which required open conversion. There were 19 postoperative complications (7.5%), three of which required reexploration for bleeding. The majority of complications were minor including 62% grade 1, 8% grade 2, 31% grade 3, and no grade 4 or 5 complications. There were no intraoperative complications in the right-sided donor group. There was a 5% complication rate for patients with a body mass index (BMI) exceeding 25. The findings showed that 11.2% of the recipients had slow graft function, and 4.4% had delayed graft function. Less than 1% of the recipients experienced ureteral stricture requiring permanent stent placement or reoperation. Overall, there was a 2% graft loss rate. CONCLUSIONS: The findings show a low rate of intraoperative and postoperative complications, most of which were minor complications. There was an increase in operative time and hospital stay in the right-sided group, but no increase in complication rate. There was no significant difference in outcome or complication rate for the overweight patients. PMID- 17334862 TI - Effect of sirolimus treatment on gene expression in renal transplant patients. AB - BACKGROUND: Sirolimus (rapamycin), a strong immunosuppressive agent, is administered to renal transplant patients to prevent rejection. The rapamycin signaling pathway [mammalian target of rapamycin (mTOR)] has been implicated in transcriptional regulation. METHODS: We used high-density oligonucleotide human microarrays to evaluate the effects of sirolimus treatment on gene expression in renal transplant patients. With this technique, we assessed selected genes in the rapamycin signaling, immunosuppression, insulin signaling, and triglyceride metabolism pathways. RESULTS: Filtered data from both treated and untreated patients showed variability within each group. Significant fold changes were observed in genes from the immunosuppression and insulin signaling pathways but not the rapamycin signaling pathway. The triglyceride metabolism pathway revealed a significant reduction of message levels in lipoprotein and triglyceride synthesis genes. CONCLUSIONS: These results show that using oligonucleotide microarrays to analyze the effects of sirolimus treatment in patients with renal transplant is an effective way to evaluate gene message levels in multiple pathways. PMID- 17334863 TI - Barrett's Esophagus, fundoplication, and cancer. PMID- 17334858 TI - High-density universal 16S rRNA microarray analysis reveals broader diversity than typical clone library when sampling the environment. AB - Molecular approaches aimed at detection of a broad-range of prokaryotes in the environment routinely rely on classifying heterogeneous 16S rRNA genes amplified by polymerase chain reaction (PCR) using primers with broad specificity. The general method of sampling and categorizing DNA has been to clone then sequence the PCR products. However, the number of clones required to adequately catalog the majority of taxa in a sample is unwieldy. Alternatively, hybridizing target sequences to a universal 16S rRNA gene microarray may provide a more rapid and comprehensive view of prokaryotic community composition. This study investigated the breadth and accuracy of a microarray in detecting diverse 16S rRNA gene sequence types compared to clone-and-sequencing using three environmental samples: urban aerosol, subsurface soil, and subsurface water. PCR products generated from universal 16S rRNA gene-targeted primers were classified by using either the clone-and-sequence method or by hybridization to a novel high-density microarray of 297,851 probes complementary to 842 prokaryotic subfamilies. The three clone libraries comprised 1391 high-quality sequences. Approximately 8% of the clones could not be placed into a known subfamily and were considered novel. The microarray results confirmed the majority of clone-detected subfamilies and additionally demonstrated greater amplicon diversity extending into phyla not observed by the cloning method. Sequences matching operational taxonomic units within the phyla Nitrospira, Planctomycetes, and TM7, which were uniquely detected by the array, were verified with specific primers and subsequent amplicon sequencing. Subfamily richness detected by the array corresponded well with nonparametric richness predictions extrapolated from clone libraries except in the water community where clone-based richness predictions were greatly exceeded. It was concluded that although the microarray is unreliable in identifying novel prokaryotic taxa, it reveals greater diversity in environmental samples than sequencing a typically sized clone library. Furthermore, the microarray allowed samples to be rapidly evaluated with replication, a significant advantage in studies of microbial ecology. PMID- 17334864 TI - Outcomes of hepatectomy for hepatolithiasis. AB - AIM: Surgical and nonsurgical procedures for management of hepatolithiasis have been reported. The aim of this study was to evaluate immediate and long-term results of hepatectomy as treatment for hepatolithiasis. MATERIALS AND METHODS: Immediate and long-term outcomes of 123 consecutive patients who underwent hepatectomy for hepatolithiasis at our institution from 2000 to 2005 were analyzed retrospectively. Acute cholangitis was the major presenting symptom (in 106 out of 123, 86.2% of cases). RESULTS: The immediate stone clearance rate was 92.7% (114 out of 123) and final stone clearance rate was 96% (118 out of 123) after subsequent T-tube route or endoscopic retrograde cholangiopancreatography (ERCP). Residual stones were identified in 5 patients (4%). The surgical morbidity and mortality rates were 33.3% (41 out of 123) and 1.6% (2 out of 123) respectively. Of the 123 patients, 3 (2.4%) had associated cholangiocarcinoma at the time of hepatectomy. With a median follow-up of 40.3 months (range 5-58), a recurrent stone developed in 7 patients (5.7%) and cholangiocarcinoma in 2 (1.6%). Ten patients died during the follow-up period, with 4 of them (out of 123, 3.2%) due to recurrent stone with sepsis. CONCLUSION: Hepatectomy is a safe and effective treatment for hepatolithiasis, with a high stone clearance rate and fair rate of surgical complications. Recurrent stone-induced sepsis and cholangiocarcinoma are the major factors compromising long-term survival in these patients. PMID- 17334866 TI - End-to-end compression anastomosis of the rectum: a pig model. AB - BACKGROUND: Generations of investigators have attempted to achieve compression bowel anastomosis by a sutureless device, providing temporary support to the tissue and facilitating the natural healing process. The biocompatibility of nickel-titanium alloy has made it attractive for use in medical implants and devices, and several studies have described the creation of a side-to-side compression anastomosis in colon surgery with a nickel-titanium clip. We evaluated the feasibility and safety of a newly designed gun for applying a nickel-titanium compression anastomosis ring (CAR) to create an end-to-end colorectal anastomosis in a porcine model. MATERIALS AND METHODS: A segment of the proximal rectum was resected in 25 pigs. The bowel ends were anastomosed transanally by an end-to-end CAR device. The animals' follow-up continued for up to 8 weeks, and included general health status, weight gain, blood tests, and abdominal X-ray. They were then sacrificed. The anastomoses were studied for burst pressure, anastomotic index, and histopathology. RESULTS: One pig died due to iatrogenic bowel injury unrelated to the CAR device. There was no other morbidity/mortality. The other animals recovered and gained weight. Burst pressure studies demonstrated a minimum pressure of 160 mmHg at time point 0 that escalated quickly to >300 mmHg. The mean anastomotic index after 8 weeks was 0.81. Histologic evaluation revealed minimal inflammation and minimal fibrosis at the anastomosis site. CONCLUSION: The principles of compression anastomosis are better executed with the use of memory shape alloys. The promising results of this novel technique should encourage further studies of this technology. PMID- 17334865 TI - Factors predicting postoperative infectious complications and early induction of inflammatory mediators in ulcerative colitis patients. AB - BACKGROUND: Positive outcomes after restorative proctocolectomy are compromised by a number of specific septic complications. However, there is no useful perioperative marker predicting postoperative infectious complications (PICs) in steroid overdosed patients with ulcerative colitis (UC). METHODS: To determine factors associated with PICs and their relation to circulating levels of pro- and anti-inflammatory cytokines and neutrophil elastase (NE), we obtained perioperative blood samples from 60 UC patients. RESULTS: Postoperative infectious complications were identified in 47% of cases. Patients who developed PICs had significantly longer disease duration, had been administered a greater total preoperative dosage of prednisolone, and had a higher body mass index. Logistic regression analysis showed that the total preoperative dosage of prednisolone was independently associated with the development of PICs. These patients showed suppressed systemic inflammation and pro- and anti-inflammatory cytokine induction. An early increase in the NE level was found to be predictive of PICs in the high-dose group, whereas there was no significant difference in neutrophil counts between the high- and low-dose groups. CONCLUSIONS: Circulating NE levels in the early postoperative period might be a useful predictor of PICs in immune-controlled UC patients who received high doses of steroids. PMID- 17334867 TI - Surgical and interventional visceral revascularization for the treatment of chronic mesenteric ischemia--when to prefer which? AB - BACKGROUND: The purpose of the present study was to compare surgical and endovascular revascularization for chronic mesenteric ischemia (CMI). METHODS: Forty-nine patients underwent surgical (SG) or endovascular (EG) treatment. Relief of symptoms was considered the primary endpoint; patency, morbidity, and mortality were secondary endpoints. For statistical analysis, significance was assumed if P values < or = 0.05. RESULTS: Twenty-six patients (53%) underwent surgical revascularization; 23 patients (47%), endovascular repair. Mean follow up was 25 +/- 21 months (SG) versus 10 +/- 10 (EG) months (P = 0.07). Except for body mass indices (SG 18.9 +/- 2.7 versus EG 23.6 +/- 4.8; P = 0.001), preoperative data were comparable. Freedom from symptoms was 100% (SG) versus 90% (EG) after intervention (P = 0.194), and 89% (SG) versus 75% (EG) at the end of follow-up. Reocclusion or re-stenosis occurred in 8% (SG) versus 25% (EG) (log rank test: P = 0.003), and mesenteric ischemia developed in 0% (SG) versus 9% (EG) (P = 0.04). Reintervention for CMI was required in 0% (SG) versus 13% (EG) (P = 0.01). Surgical patients experienced more early complications (42% versus EG 4%; P = 0.02) and longer hospital stays (11.6 +/- 10.9 days versus EG 1.3 +/- 0.5 days; P < 0.001). Overall mortality at the end of follow-up was 31% (SG) versus 4% (EG) (log-rank test: P = 0.08), including all patients with combined open mesenteric and aortic reconstruction (P = 0.001). CONCLUSIONS: Surgical treatment has superior long-term patency and requires fewer reinterventions, but it is also more invasive with greater morbidity and mortality compared to endovascular treatment. Endovascular techniques may be preferable in patients with significant co-morbidities, concomitant aortic disease, or indeterminate symptoms. PMID- 17334868 TI - Packing for control of hemorrhage in major liver trauma. AB - BACKGROUND: Packing for complex liver injuries has been associated with an increased risk of abdominal sepsis and bile leaks. The aim of the present study was to determine the optimum timing of pack removal and to assess whether the total duration of packing increases the incidence of these complications. METHODS: The study was based on a retrospective review of all patients requiring liver packing over an 8-year period in a level 1 trauma center. RESULTS: Ninety three (17%) of 534 liver injuries identified at laparotomy required perihepatic packing. Penetrating and blunt trauma occurred in 72 (77%) and 21 (23%), respectively. The mean total duration of packing was 2.4 days (range: 0.5-6.0 days). There was no association between the total duration of packing and the development of liver-related complications (P = 0.284) or septic complications (P = 0.155). Early removal of packs at 24 h was associated with a higher rate of re bleeding than removal of packs at 48 h (P = 0.006). CONCLUSIONS: The total duration of liver packing does not result in an increase in septic complications or bile leaks. The first re-look laparotomy should only be performed after 48 h. An early re-look at 24 h is associated with re-bleeding and does not lead to early removal of liver packs. PMID- 17334870 TI - Appendectomy versus antibiotic treatment in acute appendicitis: a prospective multicenter randomized controlled trial. PMID- 17334871 TI - The radiology digital dashboard: effects on report turnaround time. AB - As radiology departments transition to near-complete digital information management, work flows and their supporting informatics infrastructure are becoming increasingly complex. Digital dashboards can integrate separate computerized information systems and summarize key work flow metrics in real time to facilitate informed decision making. A PACS-integrated digital dashboard function designed to alert radiologists to their unsigned report queue status, coupled with an actionable link to the report signing application, resulted in a 24% reduction in the time between transcription and report finalization. The dashboard was well received by radiologists who reported high usage for signing reports. Further research is needed to identify and evaluate other potentially useful work flow metrics for inclusion in a radiology clinical dashboard. PMID- 17334872 TI - A dynamical model of lipoprotein metabolism. AB - We present a dynamical model of lipoprotein metabolism derived by combining a cascading process in the blood stream and cellular level regulatory dynamics. We analyse the existence and stability of equilibria and show that this low dimensional, nonlinear model exhibits bistability between a low and a high cholesterol state. A sensitivity analysis indicates that the intracellular concentration of cholesterol is robust to parametric variations while the plasma cholesterol can vary widely. We show how the dynamical response to time-dependent inputs can be used to diagnose the state of the system. We also establish the connection between parameters in the system and medical and genetic conditions. PMID- 17334873 TI - MR imaging of the peritoneal spread of malignancy. AB - MR imaging provides a highly sensitive and accurate means to depict tumor involving the peritoneum and bowel serosa. The ability of MR imaging to depict subtle peritoneal metastases plays a critical role in diagnosing and monitoring the oncologic patient with known or suspected peritoneal spread of malignancy. In this review I will describe the mechanisms of peritoneal tumor spread, and MR techniques and protocols for peritoneal imaging. A detailed description of the MR appearance of peritoneal tumor at different anatomic sites will be provided followed by a discussion of clinical applications for MR imaging of peritoneal malignancy. PMID- 17334875 TI - Portosystemic shunt on CT during arterial portography: prevalence in patients with and without liver cirrhosis. AB - BACKGROUND: To review various portosystemic shunts (PS) and to evaluate their prevalence by CT during arterial portography (CTAP) using a multidetector-row CT (MDCT). METHODS: CTAP of 116 patients (liver cirrhosis 70 patients, non-liver cirrhosis 46 patients) was retrospectively reviewed. CTAP was performed with the catheter placed in the superior mesenteric artery using MDCT. Axial CT images of 0.625- and 3.75- or 2.5-mm thickness were obtained. Multiplanar reformation images and maximum intensity projection images were subjected to review. RESULTS: A part of the veins in the ileocecal region drained into the right renal vein or the inferior vena cava (IVC) via the right gonadal vein in 57 patients (81%). A part of the veins of the ascending colon drained via the right renal capsular vein into the IVC in 37 patients (53%). In 46 patients without liver cirrhosis, the right gonadal and right renal capsular veins were opacified on CTAP in 22 patients (48%) and 20 patients (43%), respectively. CONCLUSIONS: Portosystemic shunts in retroperitoneum were frequently recognized on CTAP images in patients with liver cirrhosis. The right gonadal vein and the right renal capsular vein were the most frequent routes of the portosystemic shunts. They may exist in physiological condition. PMID- 17334874 TI - Esophageal achalasia: comparison of fluoroscopically-guided double vs. endoscopically-guided single balloon dilation. AB - PURPOSE: To compare the long-term clinical effectiveness of fluoroscopically guided double and endoscopically guided single balloon dilations in esophageal achalasia. MATERIALS AND METHODS: Thirty-two fluoroscopically guided balloon dilations were performed in 21 patients (group A) and 48 endoscopically guided balloon dilations were performed in 37 patients (group B). The double balloon dilation technique (10 + 20-mm, 15 + 20-mm or 20 + 20-mm in diameter), with preceding single balloon dilation (10, 15, or 20-mm in diameter), was used in group A, whereas the single balloon dilation technique (30, 35, or 40-mm in diameter) with gradually increased internal pressure was used in group B. Technical success, clinical success, complications, and primary/secondary patency rates were compared between the two groups. RESULTS: All procedures were technically successful without esophageal perforation. Clinical success was achieved in 97% (31/32) and 92% (44/48) of balloon dilations in groups A and B, respectively. The symptomatic improvement in dysphagia was significantly higher in group A than in group B. Incidence of complications was the same (18.8%) in both groups. Group A showed significantly longer primary and secondary patency periods than did group B (P < 0.05). CONCLUSION: Fluoroscopically guided double balloon dilation has greater long-term effectiveness than endoscopically guided single balloon dilation in the treatment of esophageal achalasia. PMID- 17334876 TI - Perianal fistulas in Crohn's disease: MRI diagnosis and surgical planning: MRI in fistulazing perianal Crohn's disease. AB - Crohn's disease is a chronic, transmural inflammatory process of the gastrointestinal tract. It often affects the colon with the perianal area. The most common intestinal manifestations include external and/or internal fistulas and abscesses. Assessment of the activity of perianal fistulas in the course of Crohn's disease seems to be an important factor influencing therapeutic approach. Fistula's activity is evaluated by such methods as magnetic resonance imaging, anal ultrasound and examination under anaesthesia. Usefulness of imaging methods in the diagnosis of fistulas still remains to be defined.MRI is used to present a wide spectrum of perianal fistulazing Crohn's disease. Additionally, it is an important instrument revealing location, extent and severity of inflammation. It is also very helpful to detect clinically silent sepsis related to small, local inflammation. The most common method used in MR imaging to assess topography of a fistula's track, is Parks' classification.Clinical indications to MRI may include follow-up studies of a diagnosed disease, classification of fistulas' subtypes in the course of Crohn's disease, determination of the extent of fistulas' tracts and spread of an inflammatory process what can guide surgical procedures. PMID- 17334877 TI - Foreign body granuloma of activated charcoal. AB - We present foreign body granulomas induced by activated charcoal from intraperitoneal chemotherapy and mimicked peritoneal metastases in the patients with gastric cancer. On CT, they were manifested as a peritoneal mass or thickening with variable shapes, including oval, round, bizarre, linear and even a molded shape due to where they were lodged, such as the pelvis and paracolic gutter. All the lesions showed high attenuation relative to muscle on the precontrast CT and showed positive findings on PET/CT. PMID- 17334878 TI - Intrahepatic portosystemic venous shunts: Color Doppler sonography. AB - BACKGROUND: The aim of the study was to evaluate intrahepatic portosystemic venous shunts (IPSVS) patterns and to determine the role of Color Doppler sonography in the diagnosis and evaluation of related hemodynamic changes in portal perfusion. METHODS: Sonography and Color Doppler imaging were performed in nine patients with IPSVS. Type and Doppler waveform of the shunt were determined; velocity measurements in the portal trunk and portal branches were studied to evaluate the effects of the shunt on intrahepatic circulation. Computed tomography was performed in six patients, magnetic resonance imaging in three patients, and angiography in two patients. RESULTS: The shunt between the portal and hepatic veins was aneurismal in six patients, while localized peripheral shunt with multiple tortuous vessels in one hepatic segment was observed in three patients. The shunts showed continuous low velocity spectral tracings and in the aneurismal shunts a low velocity bi-directional or helicoidal flow was detected. The feeding portal branches and the draining hepatic veins showed anomalous Doppler tracings and alterations of intrahepatic portal perfusion were observed in three cases. CONCLUSION: Color Doppler is essential for proper diagnosis of IPSVS and for evaluation of related hemodynamic changes in portal perfusion. PMID- 17334879 TI - Influence of estradiol on vascular endothelial growth factor expression in bone: a study in Gottingen miniature pigs and human osteoblasts. AB - Ovariectomy (OVX) in animal models is an accepted method to simulate postmenopausal osteoprosis. Vascular endothelial growth factor (VEGF) has been recently shown to play an important role during endochondral bone formation, hypertrophic cartilage remodeling, ossification, and angiogenesis. We hypothesized that reduced VEGF expression in bone contributes to OVX-induced bone loss and tested it in a miniature pig model and in vitro using human osteoblasts. Seventeen primiparous sows (Gottingen miniature pigs) were allocated to two experimental groups when they were 30 months old: a control group (n = 9) and an OVX group (n = 8). After 15 months, VEGF levels in lumbar vertebrae were measured by enzyme-linked immunosorbent assay and verified by Western blot analysis. VEGF and its receptor (VEGFR) were localized by immunohistochemistry. Expression of VEGF mRNA was analyzed by real-time reverse-transcription polymerase chain reaction. Differently sulfated glycosaminoglycans were localized in subchondral bone histochemically. Osteoblasts were immunopositive for VEGF. VEGF concentration in the vertebra was 27% lower in OVX miniature pigs. VEGFR-2 could be immunostained on osteoblasts. VEGF mRNA and protein were detectable in the lumbar vertebrae of all animals. In subchondral trabecular bone of OVX animals, significantly more islands of mineralized cartilage containing chondroitin 4- and 6-sulfate or keratan sulfate occurred compared to the control group. The occurrence of remnants of mineralized cartilage in subchondral bone of the OVX group may be caused by a delayed bone turnover due to low VEGF levels. In vitro experiments revealed an increase of VEGF in the supernatant of osteoblasts after incubation with estradiol. In conclusion, estrogen seems to be a key factor for regulation of VEGF expression in bone. Loss of VEGF due to menopause may be a reason for reduction of bone density. PMID- 17334880 TI - CYP3A7*1C polymorphism, serum dehydroepiandrosterone sulfate level, and bone mineral density in postmenopausal women. AB - The CYP3A7 enzyme metabolizes some steroid hormones, including dehydroepiandrosterone sulfate (DHEAS). The age-related decline of serum DHEAS levels is believed to contribute to osteoporosis. Previously, the CYP3A7*1C polymorphism has been shown to cause a persistent high CYP3A7 enzyme activity, resulting in lower levels of DHEAS in men. We hypothesized that the CYP3A7*1C polymorphism might contribute to bone loss through decreased levels of serum DHEAS in postmenopausal women. Postmenopausal women (n = 319) were divided into two subgroups: 217 with osteoporosis and 102 healthy controls. Genotyping, serum DHEAS measurement, and osteodensitometry of the lumbar spine and femoral neck were carried out in all subjects. Homozygous CYP3A7*1C carriers had significantly lower BMD at the lumbar spine compared to wild types (T score -3.27 +/- 1.02 in CYP3A7*1C homozygous mutants vs. -1.35 +/- 1.53 in wild types, P = 0.041). This association remained significant after adjustment for menopausal age, serum DHEAS level, alcohol consumption, steroid intake, smoking habits, and previous fractures. No association was found between genotypes and serum DHEAS levels in the total study population or in the subgroups. Serum DHEAS levels correlated positively with bone mineral density at the lumbar spine (r = 0.59, P = 0.042) after correction for age. Our data suggest that the CYP3A7 polymorphism might have an influence on bone mass at the lumbar spine independently of serum DHEAS concentrations. PMID- 17334882 TI - [Hospital hygiene: possibilities and limits of consultation with the Robert Koch Institute concerning routine inquiries]. PMID- 17334881 TI - Cyclooxygenase-2 inhibition delays the attainment of peak woven bone formation following four-point bending in the rat. AB - Fracture healing is retarded in the presence of cyclooxygenase-2 (COX-2) inhibitors, demonstrating an important role of COX-2 in trauma-induced woven bone adaptation. The aim of this experiment was to determine the influence of COX-2 inhibition on the remodeling and consolidation of nontraumatic woven bone produced by mechanical loading. A periosteal woven bone callus was initiated in the right tibia of female Wistar rats following a single bout of four-point bending, applied as a haversine wave for 300 cycles at a frequency of 2 Hz and a magnitude of 65 N. Daily injections of vehicle (VEH, polyethylene glycol) or the COX-2 inhibitor 5,5-dimethyl-3-3(3 fluorophenyl)-4-(4-methylsulfonal)phenyl-2(5H) furanone (DFU, 2.0 mg . kg(-1) and 0.02 mg . kg(-1) i.p.), commenced 7 days postloading, and tibiae were examined 2, 3, 4, and 5 weeks postloading. Tibiae were dissected, embedded in polymethylmethacrylate, and sectioned for histomorphometric analysis of periosteal woven bone. No significant difference in peak woven bone area was observed between DFU-treated and VEH rats. However, treatment with DFU resulted in a temporal defect in woven bone formation, where the achievement of peak woven bone area was delayed by 1 week. Woven bone remodeling was observed in DFU-treated rats at 21 days postloading, demonstrating that remodeling of the periosteal callus is not prevented in the presence of a COX-2 inhibitor in the rat. We conclude that COX-2 inhibition does not significantly disrupt the mechanism of woven bone remodeling but alters its timing. PMID- 17334883 TI - [The National Programme for Disease Management Guidelines. Goals, contents, patient involvement]. AB - The Programme for National Disease Management Guidelines (German DM-CPG Programme) aims at the implementation of best practice recommendations for prevention, acute care, rehabilitation and chronic care. The programme, focussing on high priority healthcare topics, has been sponsored since 2003 by the German Medical Association (BAEK), the Association of the Scientific Medical Societies (AWMF), and by the National Association of Statutory Health Insurance Physicians (KBV). It is organised by the German Agency for Quality in Medicine, a founding member of the Guidelines International Network (G-I-N). The main objective of the programme is to establish consensus of the medical professions on evidence-based key recommendations covering all sectors of health care provision and facilitating the coordination of care for the individual patient through time and across disciplines. Within this framework experts from national patient self-help groups have been developing patient guidance based upon the recommendations for healthcare providers. The article describes goals, topics and selected contents of the DM-CPG programme - using asthma as an example. PMID- 17334884 TI - [Implementation of the new EU Bathing Water Directive in Germany]. AB - A revised version of the Bathing Water Directive 76/160/EWG has been elaborated to include scientific progress in risk assessment of bathing-related illness. The new Bathing Water Directive 2006/7/EC came into force on March 24, 2006, and will have to be implemented in the federal states within two years. The new bathing water directive contains several positive innovations which will improve a protection of the bathers namely i) health related indicators, ii) uniform detection methods, iii) requirements for active bathing water management, and iv) stricter standards for coastal waters. In Germany, the 16 federal states of the Federal Republic of Germany - the Lander - are responsible for monitoring bathing waters and for implementing the new bathing water directive into national law. A common master directive is being written by a joint working-group to ensure comparable implementation in all parts of Germany. An immediate application of the new directive is not possible since the parameter "intestinal enterococci" is currently not routinely monitored. It was decided to start monitoring according to the new directive in Germany in 2008. This will allow the first classification of bathing waters according to the new directive in 2011. PMID- 17334885 TI - [Cyanobacterial toxins in bank filtrate. Under which conditions is their elimination reliable?]. AB - Cyanobacterial toxins are substances produced by cyanobacteria or blue-green algae. They can occur in surface waters worldwide and have to be reliably removed when using affected surface waters as a drinking water source. Bank filtration has been used for 150 years for drinking water (pre-)treatment. It utilizes natural elimination processes like sorption and degradation in the sub-surface. Retention of cells on the sediment surface is the most prominent process for eliminating these primarily cell-bound toxins. Middle to coarse grained sands eliminated more than 99.9 % of intracellular toxins within the first 10 cm of flow path. Elimination of extracellular microcystin during underground passage is mainly due to biodegradation. Reversible adsorption processes do not reduce the total load but lead to longer contact times for extended biodegradation. Laboratory experiments showed that the sediment structure, i.e. high clay/silt and organic content, is crucial for maximum adsorption. However, redox conditions play an important role for degradation rates: under aerobic conditions half-lives of less than one day occurred frequently, whereas anoxic conditions resulted in lag phases of one day and more, as well as in half lives of more than 25 days. Field experiments showed that temperature is crucial for degradation velocity under natural conditions. Under optimal conditions 10 d residence time are sufficient to reduce microcystin concentrations to values below the WHO guidelines value for drinking water (1 microg/L). Under sub-optimal conditions a residence time of up to 90 days may be necessary. PMID- 17334887 TI - [Surveillance of drinking water supply systems on markets and in vehicles]. AB - The new German Drinking Water Ordinance (TrinkwV 2001) demands that the requirements of water intended for human consumption be met up to the intrinsic tap, at which the water is used. This also applies to water supply systems for food trade aboard non-stationary facilities and in vehicles for commercial purposes. In contrast to stationary units for drinking water supply, the nonstationary units relocate and the responsibility changes with each public health authority agent. Therefore, a coordinated action between the federal states is desirable and necessary. The experience of the public health departments presents many non-compliant parameters of microbiology in water supply systems on markets and in vehicles. The development of practical and consistent recommendations for the surveillance of non-stationary units is required to give consistent standards to the users. The article gives a review about legal foundations and technical rules in order to define the drinking water supply systems on markets and in vehicles in compliance with the German Drinking Water Ordinance. Examples of laboratory results from different monitoring episodes from three federal states are shown. PMID- 17334886 TI - [Testing the efficacy of disinfectants during drinking water treatment. A new experimental set-up at the German EPA (Umweltbundesamt - UBA)]. AB - A set-up for experiments in the flow-through mode was constructed in order to test the efficacy of substances used for disinfecting water during drinking water treatment. A flow-through mode - in contrast to experiments under stationary conditions (so-called batch experiments) - was chosen, because this experimental design allows experiments to be carried out under constant conditions for an extended time (up to one week) and because efficacy testing is possible repeatedly, simultaneously and under exactly the same conditions for short (about 0.5 min) and also longer (about 47 min) contact times. With this experimental design the effect of biofilms along the inner pipe surfaces can be included in the observations. The construction of the experimental set-up is based on experience with laboratory flow-through systems that were installed by the UBA's drinking water department (formerly Institute for Water-, Soil- and Air Hygiene (WaBoLu) Institute) for testing disinfection with chlorine. In the first step, a test pipe for the simulation of a water works situation was installed. Water of different qualities can be mixed in large volumes beforehand so that the experimental procedure can be run with constant water quality for a minimum of one week. The kinetics of the disinfection reaction can be observed by extracting samples from eight sampling ports situated along the test pipe. In order to assign exact residence times to each of the sampling ports, tracer experiments were performed prior to testing disinfectant efficacy. This paper gives the technical details of the experimental set-up and presents the results of the tracer experiments to provide an introduction with respect to its potential. PMID- 17334888 TI - [Assessment of so called organic trace compounds in drinking water from the regulatory, health and aesthetic-quality points of view, with special consideration given to pharmaceuticals]. AB - More than 2500 chemically defined substances are approved as drugs in Germany. Unlike agricultural pesticides, these biologically active structures are not used in open environmental compartments and therefore their environmental toxicological data base is not nearly as complete. Nevertheless, some of them become environmental contaminants after their intended use. Therefore, from the viewpoint of environmental health protection, there are gaps in their health related environmental risk assessment. Organic trace compounds that lack an adequate toxicological database, and their mixtures, in drinking water can be safely regulated and provisionally assessed by combining the "similar joint action" addition rule with the recommendation of the Federal Environment Agency of March 2003 "Assessing the presence of substances in drinking water without (adequate) toxicological database from the health point of view". The general precautionary value (Gesundheitlicher Orientierungswert GOW1=0.10 microg/l), which is a recommendation for weakly to not genotoxic compounds, re presents a workable compromise between preventive health protection, water management considerations and aesthetic quality claims (purity). Compliance with this value in the long term will only be possible if the chemical and biological degradation of pharmaceuticals and their metabolites in waste water and waste water treatment plants is effectively improved. Alternatively, there is the risk of drinking water degenerating into a sink for highly mobile, polar and persistent compounds. Their elimination at a stage as late as technical drinking water treatment would be neither close to the initial cause nor justifiable in terms of technical effectiveness. The risk assessment of their byproducts would give rise to further uncertainties. Possible conflicts with the therapeutic quality must be solved by developing substitute products which are environmentally sound. PMID- 17334889 TI - [Hygienic requirements on materials in contact with drinking water]. AB - In Germany the hygienic requirements on materials used to supply drinking water are a part of the technical standards. These regulations have to ensure that legal requirements on drinking water are met at the tap. The hygienic harmlessness is assured by requirements on the composition of materials and by test procedures including parametric limits. Historically, the requirements on different types of materials are a part of different technical standards. PMID- 17334890 TI - [Water as a reservoir for nosocomial infections in health care facilities, prevention and control]. AB - New epidemiological and microbiological investigations using molecular typing methods to link patient and environmental strains demonstrate a strong association between water-borne pathogens and nosocomial infections. Avoiding patient exposure to these pathogens results in a decreased incidence of water borne nosocomial infections. There remains a tremendous potential to reduce hospital acquired infections previously viewed as inevitable and unavoidable through intervention and preventive measures. The characteristics of water application in health care facilities, the vulnerability of patients, the spectrum of relevant pathogens and their ecologic aspects, legal issues and important measures for prevention and control are discussed. PMID- 17334891 TI - [Viruses in drinking water]. AB - Viruses in drinking water can cause infectious diseases. In the past, hepatitis A and E were the most frequently observed drinking- water-borne viral infections, but in recent years several small- and large-scale norovirus epidemics have been described, even in Europe. All virus species spread via drinking water are of fecal origin. They are regularly identified in waste water even after conventional multi-stage water treatment. The approved disinfection methods can cope with these viruses if they are not integrated in larger particles. For this reason particle separation is particularly important in water treatment. Virological tests are not reliable enough to ensure that drinking water is sufficiently virus-free. The examination of 100 mL of water for E. coli and coliform bacteria is not adequate proof either. If potentially contaminated raw water is used, consumer safety must be ensured by calculating the performance of water treatment plants on a case-by-case basis. Such a calculation takes into account the virus load of the raw water, the efficiency of the physical and chemical particle elimination steps and the effect of disinfection. Those factors which determine the effectiveness of disinfection, namely concentration and exposure time or UV radiation strength, must be adjusted according to the risk of viral infection, and calculated settings must be adhered to, even if favorable E. coli levels may make them seem excessive. PMID- 17334892 TI - [Drinking water analysis for Legionella. Suggestions for sampling, laboratory analysis and assessment]. AB - Drinking water analysis for Legionella from building installations is done quite frequently. Some questions arise from experience with this analysis. They will be discussed to allow uniform and comparable execution. Application of DIN EN ISO 19458 will lead to changes in the sampling procedure. This may make changes necessary even in current sampling and assessment programs. Concerning laboratory investigation, quality control of membrane filters and media turned out to be crucial. The assessment of quantitative results requires knowledge of the drinking water distribution system and of other facts that may be relevant for hygiene. Therefore, the assessment ought to be conducted by somebody with the respective knowledge. PMID- 17334893 TI - [Special aspects of microbiological monitoring of drinking water quality]. AB - The new drinking water ordinance (TrinkwV 2001) entered into force in 2003. In this paper we report about experiences with monitoring microbiological quality of drinking water. Special problems, for instance requirements concerning the quality of raw water, new and "old" microbiological parameters, microbiological methods, assessment of parametric values, especially in the case of values higher than the imperative value, are also described. Possible developments in this field are discussed. The paper should support microbiological laboratories, public health officers and other public authorities in monitoring and assessment of drinking water quality. PMID- 17334894 TI - [The drinking water quality in Germany in the period from 2002 to 2004. An overview]. AB - In Germany the drinking water is to be monitored regularly. The sampling frequencies and the scale of monitoring of the water supplies are provided by the Drinking Water Ordinance 2001. Taking into account the overall samples taken, the drinking water quality ranges from good to very good, and the requirements for the microbiological, chemical and physical standards have been largely satisfied, as set out by the Drinking Water Ordinance 2001. What concerns most parameters, unremarkable variations have been measured in more than 99 % of samples taken. The highest frequency of non-compliance (in 1 to 2 % of samples taken) has been found in the parameters pesticides and coliform bacteria. Some impairments of drinking water quality could be traced to house installation systems, which do not meet the commonly accepted technical rules. In general, potential danger to human health does not exist. This information is based on the report by the Ministry of Health about the quality of drinking water in Germany in the period 2002-2004. PMID- 17334895 TI - [The drinking water ordinance--successful or requiring revision?]. AB - The current regulatory approach in Germany combines regulations defined in the Drinking Water Ordinance with a comprehensive catalogue of technical rules as well as with guidelines and recommendations by the Federal Environment Agency and the Drinking Water Commission. This approach has proven successful in practice. Some parts would benefit from revision. The regulator is currently contemplating some revision in order to take experience of federal, state and local authorities as well as of water suppliers with implementation of the current Ordinance into account. The intention is improvement particularly towards reducing bureaucracy without compromising the current high level of public health protection through drinking water hygiene in Germany. PMID- 17334896 TI - Cardiac sympathetic denervation preceding motor signs in Parkinson disease. AB - There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[(18)F]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The results lead us to hypothesize that cardiac noradrenergic denervation and decreased baroreflex-cardiovagal function may occur early in the pathogenesis of PD. PMID- 17334897 TI - The relationship between cognitive dysfunction and stress sensitivity in schizophrenia: a replication study. AB - The aim of the current study was to replicate the finding that cognitive impairments are not or inversely associated with sensitivity to stress in a sample of 25 patients diagnosed with psychotic disorder. The results indicated that impairments in performance on the Trailmaking Test and the Stroop Color Word Test were inversely associated with sensitivity to stress in daily life, whereas impairment in a subtest of the Behavioral Assessment of Dysexecutive Syndrome (BADS) was not associated with stress-sensitivity. The data thus show that in some instances cognitive functioning is not, and in other instances is inversely associated with momentary sensitivity to stress. Cognitive impairment and affective reactivity thus appear to be independent or mutually exclusive mechanisms in psychosis, suggesting competing causal pathways. PMID- 17334898 TI - Seemingly minor changes to a questionnaire can make a big difference to mean scores: a cautionary tale. AB - BACKGROUND: It is not unusual for researchers to make apparently minor modifications to existing instruments without checking if this alters psychometric properties. METHOD: Equivalent items on child mental health from two different versions of the Rutter parent questionnaire were compared: items from the standard version and from a modified version. The parents of 400 children aged 5-7 years were randomised into two groups: each group completed one version of the Rutter as well as an independent measure of psychopathology (the Strengths and Difficulties Questionnaire; SDQ). RESULTS: The mean psychopathology scores of the two groups were comparable according to the SDQ but differed markedly between the two Rutter versions, principally because of changes in the response categories. Nevertheless, the validity of the two versions of the Rutter was similar as judged from Rutter-SDQ correlations. CONCLUSION: Seemingly minor changes in the wording of a measure can have a major impact on mean scores, thereby making it harder to compare or combine the results of studies using the original and the modified measure. PMID- 17334899 TI - Developing the diagnostic and statistical manual V: what will "statistical" mean in DSM-V? AB - In February of 2004, the American Psychiatric Institute for Research and Education (APIRE) hosted a Launch and Methodology Conference to discuss the role statistics might play in the eventual revision of the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the Ninth Edition of the International Classification of Diseases (ICD9). The conference consisted of talks on specific topics by statisticians and epidemiologists from North America and Great Britain, followed by group discussion by experts in nosology and psychopathology. We report here on the development of specific themes related to the future interaction between statisticians and nosologists in DSM-V development that arose as a result of that meeting. The themes are related to (1) the nature of the statistician/nosologist interaction; (2) specific areas of concern in that interaction, and (3) the use of novel and complex statistical methods to challenge and inspire new avenues of thinking among nosologists. PMID- 17334900 TI - Treatment seeking for alcohol and drug use disorders by immigrants to the Netherlands: retrospective, population-based, cohort study. AB - BACKGROUND: We compared risks of first contact with services for an alcohol use disorder (AUD) or drug use disorder (DUD) between the largest immigrant groups to the Netherlands and Dutch nationals. We tested the hypothesis that the ethnic pattern for DUD is similar to the previously demonstrated pattern for schizophrenia. METHODS: Retrospective, population-based cohort study of First Admissions to Dutch psychiatric hospitals during the period 1990-1996 (national data) and First Contacts with inpatient or outpatient centres in Rotterdam for treatment of AUD or DUD during the period 1992-2001 (Rotterdam data). RESULTS: In both datasets the risk of service contact for AUD was significantly lower in immigrants from Surinam, Turkey and Morocco than in Dutch nationals. The risk was lower or moderately higher in immigrants from western countries. Analysis of the national data showed that, compared with Dutch males, the risk of first hospital admission for DUD was higher for male immigrants from the Dutch Antilles (RR = 4.6; 95% CI: 4.0-5.3), Surinam (RR = 4.3; 3.9-4.7) and Morocco (RR = 2.3; 2.0 2.6), but not for male immigrants from Turkey (RR = 0.9; 0.7-1.1). A similar pattern was found with the Rotterdam data. Female immigrants from Surinam and the Dutch Antilles had a higher risk for DUD according to the national data, but a lower risk according to the Rotterdam data. Female immigrants from Turkey and Morocco had a lower risk (both datasets). Immigrants from western countries had a higher risk for DUD, but many had developed the disorder before emigrating. CONCLUSION: Those immigrant groups in the Netherlands that are at increased risk of schizophrenia appear also at increased risk of developing DUD, but not AUD. PMID- 17334901 TI - Analysis of methionine oxides and nitrogen-transporting amino acids in chilled and acclimated maize seedlings. AB - In maize seedlings, chilling causes a reduction of glutamine synthetase (GS) activity, while acclimation protects GS (manuscript submitted). Since ROS can oxidize both protein-bound and free Met to methionine sulfoxide (MSO) and further to methionine sulfone (MSO2, a GS inhibitor), it was hypothesized that the chilling-induced oxidative stress may cause accumulation of MSO and MSO2, thus contributing to the inactivation of GS. MSO2 preferentially inhibited the chloroplastic isoform, GS2. HPLC analysis of polar amino acids from coleoptiles + leaves, mesocotyls and roots of control, chilled, acclimated, acclimated and chilled and chilled and rewarmed plants revealed that free MSO and MSO2 do not accumulate after low temperature treatments. Nevertheless, acclimation significantly increased the expression of putative protein methionine sulfoxide reductase (PMSR), especially in mesocotyls. Different low temperature treatments caused complex changes in the profiles of N-transporting amino acids, Asp, Glu, Asn and Gln. PMID- 17334902 TI - S-adenosylmethionine and its products. AB - S-adenosylmethionine is involved in many processes, mainly methylation, polyamine synthesis and radical-based catalysis. It is synthesised through the catalysis of differently regulated enzyme forms. When it is used, the compounds formed are reutilized in different ways: in case of methylation, its end product is homocysteine, which can be remethylated to methionine, give rise to cysteine in the so-called transsulphuration pathway, or be released; in the case of polyamine synthesis, the methylthioadenosine formed is cleaved and gives rise to compounds which can be reutilized; during radical-based catalysis, 5-deoxyadenosine is formed and this, too, is cleaved and reutilized. PMID- 17334903 TI - Protective effect of oxidative stress in HaCaT keratinocytes expressing E7 oncogene. AB - In a previous study, we established a stable cell line which constitutively expresses E7 in HaCaT human keratinocyte cell line and identified various relevant factors including oxygen modulators affected by the E7 oncogene. E7 expressing HaCaT cells (HaCaT/E7) appeared to be more resistant to H2O2-induced cell death. Here, we demonstrate how E7 oncogene would modulate oxidative stress induced cell death. In addition, we verified the increased expression of catalase in the HaCaT/E7 by Western blot analysis. The results suggest that the E7 oncogene would induce higher resistance to ROS-induced cell injury in the E7 infected cells via the upregulation of catalase. To investigate these paradoxical effects of high concentrations of H2O2 (500 microM-1 mM), we examined their effects on receptor mediated apoptosis, cell death via the mitochondrial pathway and modulation of apoptosis related factors. Our results revealed that HaCaT keratinocytes infected with HPV 16 E7 oncogene modulated expressions of catalase, Bcl-xL, IL-18, Fas, Bad, and cytochrome c as well as NF-kappaB, resulting in the resistance to oxidative stress-induced cell death. PMID- 17334904 TI - Which mechanisms are involved in taurine-dependent granulocytic immune response or amino- and alpha-keto acid homeostasis? AB - We examined the effects of beta-alanine (taurine analogue and taurine transport antagonist), taurine (regarding its role in neutrophil (PMN) immunonutrition) and taurine combined either with L-NAME (inhibitor of *NO-synthase), SNAP (*NO donor), DON (glutamine-analogue and inhibitor of glutamine-requiring enzymes), DFMO (inhibitor of ornithine-decarboxylase) and beta-alanine on neutrophil amino- and alpha-keto acid profiles or important PMN immune functions in order to establish whether taurine transport-, nitric oxide-, glutamine- or ornithine dependent mechanisms are involved in any of the taurine-induced effects. According to the present findings, the taurine-mediated effect appears to be based primarily on a modulation of important transmembraneous transport mechanisms and only secondarily on directly or indirectly induced modifications in intragranulocytic amino- and alpha-keto acid homoeostasis or metabolism. Although a direct relation to the parallel observed immunological modifications can only be presumed, these results show very clearly that compositional modifications in the free intragranulocytic amino- and alpha keto-acid pools coinciding with changes in intragranulocytic taurine levels are relevant metabolic determinants that can significantly influence the magnitude and quality of the granulocytic immune response. PMID- 17334905 TI - Mass spectrometric analysis of protein histidine phosphorylation. AB - Protein histidine phosphorylation is now recognized as an important form of post translational modification. The acid-lability of phosphohistidine has meant that this phosphorylation has not been as well studied as serine/threonine or tyrosine phosphorylation. We show that phosphohistidine and phosphohistidine-containing phosphopeptides derived from proteolytic digestion of phosphohistone H4 are detectable by ESI-MS. We also demonstrate reverse-phase HPLC separation of these phosphopeptides and their detection by MALDI-TOF-MS. PMID- 17334906 TI - Methods for syntheses of N-methyl-DL-aspartic acid derivatives. AB - A novel practical method for the synthesis of N-methyl-DL-aspartic acid 1 (NMA) and new syntheses for N-methyl-aspartic acid derivatives are described. NMA 1, the natural amino acid was synthesized by Michael addition of methylamine to dimethyl fumarate 5. Fumaric or maleic acid mono-ester and -amide were regioselectively transformed into beta-substituted aspartic acid derivatives. In the cases of maleamic 11a or fumaramic esters 11b, the alpha-amide derivative 13 was formed, but hydrolysis of the product provided N-methyl-DL-asparagine 9 via base catalyzed ring closure to DL-alpha-methylamino-succinimide 4, followed by selective ring opening. Efficient methods were developed for the preparation of NMA-alpha-amide 13 from unprotected NMA via sulphinamide anhydride 15 and aspartic anhydride 3 intermediate products. NMA diamide 16 was prepared from NMA dimethyl ester 6 and methylamino-succinimide 4 by ammonolysis. Temperature dependent side reactions of methylamino-succinimide 4 led to diazocinone 18, resulted from self-condensation of methylamino-succinimide via nucleophyl ring opening and the subsequent ring-transformation. PMID- 17334907 TI - Norovirus mixed infection in an oyster-associated outbreak: an opportunity for recombination. AB - We describe an outbreak of gastroenteritis in which the nucleic acid of three distinct noroviruses was amplified from the same fecal sample. To enable the separate amplification of each virus, an inclusion/exclusion RT-PCR primer design strategy was developed. This paired a virus-specific exclusion primer (designed with the exact sequence of one virus in a region displaying low conservation among the three viruses) with a virus-nonspecific inclusion primer (designed in a conserved region). Thus, in each reaction the exclusion primer provided specificity for a single virus, and the inclusion primer increased the sensitivity and allowed hybridization in a region of unknown sequence. Analysis of the partial genomic sequences of the three viruses (3.6-3.8 kb) indicated that each virus belonged to a separate genogroup II cluster, and each displayed evidence of a potential recombination event when the sequences were compared with other published norovirus sequences. Our results, which show a mixed norovirus infection in a single individual, confirm the need to be aware of the possibility of mixed norovirus infections, and of the possibility of genomic recombination causing anomalies in phylogenetic analyses in such instances. PMID- 17334908 TI - Sex differences in two event-related potentials components related to semantic priming. AB - Although sex differences in language processing are well documented in behavioral studies, only a few electrophysiological studies have explored this topic. We analyzed sex differences in two language-related components of event-related potentials (ERPs): the N400 and the Late Positive Complex (LPC). Ten men and 10 women, matched by age and handedness, participated in the study. Two semantic priming paradigms were presented: word pairs (60 congruent and 60 incongruent) and sentences (50 with congruent and 50 with incongruent ending words). In addition, the effect of context was investigated by a comparison between ERP effects obtained in single word priming and sentential priming. The N400 effect was earlier and larger in women, and the LPC effect was larger in men. Furthermore, the LPC effect in men, but not in women, was much larger with sentence priming than with word priming, suggesting that the LPC effect may be more dependent on context in men than in women. The opposite sex difference on the two ERP components indicates different underlying mechanisms. While the LPC effect is thought to be generated by purely explicit mechanisms, such as postlexical integrative processes, the N400 effect may be also governed by prelexical implicit and explicit mechanisms. Our results were consistent with the notion of more automated processing of language in women than in men. PMID- 17334909 TI - Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. AB - This review attempts to provide a comprehensive overview of the biology of the physiologically and pharmacologically important transport system termed the "reduced folate carrier" (RFC). The ubiquitously expressed RFC has unequivocally established itself as the major transport system in mammalian cells and tissues for a group of compounds including folate cofactors and classical antifolate therapeutics. Loss of RFC expression or function may have potentially profound pathophysiologic consequences including cancer. For chemotherapeutic antifolates used for cancer such as methotrexate or pemetrexed, synthesis of mutant RFCs or loss of RFC transcripts and proteins results in antifolate resistance due to incomplete inhibition of cellular enzyme targets and insufficient substrate for polyglutamate synthesis. Since RFC was first cloned in 1994, tremendous advances have been made in understanding the complex transcriptional and posttranscriptional regulation of RFC, in identifying structurally and functionally important domains and amino acids in the RFC molecule as a prelude to establishing the mechanism of transport, and in characterizing the molecular defects in RFC associated with loss of transport in antifolate resistant cell line models. Many of the insights gained from laboratory models of RFC portend opportunities for modulating carrier expression in drug resistant tumors, and for designing a new generation of agents with improved transport by RFC or substantially enhanced transport by other folate transporters over RFC. Many of the advances in the basic biology of RFC in cell line models are now being directly applied to human cancers in the clinical setting, most notably pediatric acute lymphoblastic leukemia and osteogenic sarcoma. PMID- 17334912 TI - Sex selective feticide in India. AB - Regarding sex selective abortion in India, all are aware of exclusive female disadvantage. And yet few study reported sizeable selective male feticide as such. This exercise reveals that: (1) the age-old son-preference has slightly declined on the end of the twentieth century, and (2) a substantial selective male feticide are also being committed annually, of course, along with larger selective female feticide. PMID- 17334911 TI - Thiopurine methyltransferase activity in Spain: a study of 14,545 patients. AB - We sought to assess the activity of thiopurine methyltransferase (TPMT) in 14,545 Spanish patients with different diseases amenable to treatment with azathioprine/6-mercaptopurine (6-MP), and to evaluate the proportion of patients with low TPMT activity and therefore a higher risk of myelotoxicity with these drugs. TPMT activity in red blood cells (RBCs) was measured by a radiochemical method. The association between several clinical variables and TPMT activity was assessed by multiple linear regression. We included 14,545 patients: autoimmune hepatitis (n=359 patients), inflammatory bowel disease (n=7,046), multiple sclerosis (n = 814), myasthenia gravis (n=344), pemphigus (n=133), and other diseases (n=5,849). Mean TPMT activity was 20.1 +/- 6 U/mL, but differed depending on the disease (P<.001). TPMT distribution was low (<5) in 0.5%; intermediate (5.0-13.7) in 11.9%; or high (>or=13.8) in 87.6%. Only when TPMT activity was considered separately in each disease did it reveal a normal distribution. In the multivariate analysis, gender, hematocrit, and treatment with 5-aminosalicylates/steroids/azathioprine/6-MP statistically influenced TPMT activity, although, probably, in a clinically irrelevant manner. This study shows, in a large sample of 14,545 patients, that 0.5% had low TPMT activity, indicating a higher risk of myelotoxicity with azathioprine/6-MP, a figure similar or slightly higher than that reported in other areas. Nevertheless, the trimodal distribution of TPMT activity varied depending on disease, and the proportion of patients with low activity values ranged from 0-0.8%. The drugs prescribed for the treatment of autoimmune diseases, including azathioprine/6-MP, modified TPMT activity, but the magnitude of this effect was very small and the differences found are probably irrelevant from the clinical point of view. PMID- 17334913 TI - First-degree atrioventricular block. Clinical manifestations, indications for pacing, pacemaker management & consequences during cardiac resynchronization. AB - Marked first-degree AV block (PR> or =0.30 s) can produce a clinical condition similar to that of the pacemaker syndrome. Clinical evaluation often requires a treadmill stress test because patients are more likely to become symptomatic with mild or moderate exercise when the PR interval cannot adapt appropriately. Uncontrolled studies have shown that many such symptomatic patients with normal left ventricular (LV) function improve with conventional dual chamber pacing (Class IIa indication). In contrast, marked first-degree AV block with LV systolic dysfunction and heart failure is still a Class IIb indication, a recommendation that is now questionable because a conventional DDD(R) pacemaker would be committed to right ventricular pacing (and its attendant risks) virtually 100% of the time. It would seem prudent at this juncture to consider a biventricular DDD device in this situation. Patients with suboptimally programmed pacemakers may develop functional atrial undersensing because the P wave tends to migrate easily into the postventricular atrial refractory period (PVARP). Retrograde vetriculoatrial conduction block is uncommon in marked first-degree AV block so a relatively short PVARP can often be used at rest with little risk of endless loop tachycardia. The usefulness of a short PVARP may be negated by special PVARP functions in some pulse generators designed to time out a long PVARP at rest and a gradually shorter one with activity. First-degree AV block during cardiac resynchronization therapy (CRT) predisposes to loss of ventricular resynchronization during biventricular pacing because it favors the initiation of electrical "desynchronization" especially in association with a relatively fast atrial rate and a relatively slow programmed upper rate. Patients with first degree AV block have a poorer outcome with CRT than patients with a normal PR interval, a response that may involve several mechanisms. (1) The long PR interval may be a marker of more advanced heart disease. (2) Patients with first degree AV block may experience more episodes of undetected "electrical desynchronization". (3) "Concealed resynchronization" whereupon ventricular activation in patients with a normal PR interval may result from fusion of electrical wavefronts coming from the right bundle branch and the impulse from the LV electrode. The resultant hemodynamic response may be superior because the detrimental effects of right ventricular stimulation (required in the setting of a longer PR interval) are avoided. PMID- 17334914 TI - Fatty acid efficiency profile in uncoupling of Acanthamoeba castellanii mitochondria. AB - A profile of free fatty acid (FFA) specificity in Acanthamoeba castellanii mitochondrial uncoupling is described. The FFA uncoupling specificity was observed as different abilities to stimulate resting respiration, to decrease resting membrane potential, and to decrease oxidative phosphorylation efficiency. Tested unsaturated FFA (C18-20) were more effective as uncouplers and protonophores when compared to tested saturated FFA (C8-18), with palmitic acid (C16:0) as the most active. As FFA efficiency in mitochondrial uncoupling is related to physiological changes of fatty acid composition (and thereby FFA availability) during growth of amoeba cells, it could be a way to regulate the activity of an uncoupling protein and thereby the efficiency of oxidative phosphorylation during a cell life of this unicellular organism. PMID- 17334915 TI - Mitochondria are targets of photodynamic therapy. AB - Photodynamic Therapy (PDT) is an evolving cancer treatment that depends on three known and variable components: photosensitizer, light and oxygen. Optimization of these variables yields reactive oxygen species, mainly singlet oxygen, that damage cellular components leading to cytotoxicity. Our research has demonstrated that porphyrin sensitizers, in particular, significantly inhibit the inner mitochondrial membrane enzymes cytochrome c oxidase and F(0)F(1) ATP synthase. These results were obtained from an in vivo-in vitro experimental protocol that exposes sensitizers to metabolic and pharmacokinetic events. The resulting inhibition of oxidative phosphorylation was expected to reduce ATP levels, which were quantitated in cells and were confirmed by (31)P-NMR spectroscopy of tumors in situ in animals treated with PDT. Based on these findings, and more recent investigations of apoptosis, there is little doubt that mitochondria are critical targets in the actions of PDT. PMID- 17334916 TI - Changes in cancer-related risk perception and smoking across time in newly diagnosed cancer patients. AB - We examine the bidirectional relationships between cancer risk perceptions and smoking behavior among newly diagnosed cancer patients (N=188) during hospitalization for surgical resection, and at three and 12 months subsequently. Those with higher perceptions of risk for developing another cancer at three months were most likely to abstain from smoking by twelve months. Patients were relatively accurate in their cancer risk perceptions, with relapsers and continuous smokers reporting higher levels of risk perceptions at twelve months. Finally, those who quit smoking by 12 months felt at lower risk for developing cancer by 12 months. None of these relationships were significant between baseline and three months. Results indicate that perceived risk of cancer recurrence may be clinically useful in motivating smoking cessation after the acute cancer treatment phase is over. This study justifies an expanded theoretical framework attending to the distinct, prospective influences of illness risk perceptions on health behavior, and of health behavior on illness risk perceptions. PMID- 17334917 TI - Methyl 2,4,6-decatrienoates attract Stink bugs and tachinid parasitoids. AB - Halyomorpha halys (Stal) (Pentatomidae), called the brown marmorated stink bug (BMSB), is a newly invasive species in the eastern USA that is rapidly spreading from the original point of establishment in Allentown, PA. In its native range, the BMSB is reportedly attracted to methyl (E,E,Z)-2,4,6-decatrienoate, the male produced pheromone of another pentatomid common in eastern Asia, Plautia stali Scott. In North America, Thyanta spp. are the only pentatomids known to produce methyl 2,4,6-decatrienoate [the (E,Z,Z)-isomer] as part of their pheromones. Methyl 2,4,6-decatrienoates were field-tested in Maryland to monitor the spread of the BMSB and to explore the possibility that Thyanta spp. are an alternate host for parasitic tachinid flies that use stink bug pheromones as host-finding kairomones. Here we report the first captures of adult and nymph BMSBs in traps baited with methyl (E,E,Z)-2,4,6-decatrienoate in central Maryland and present data verifying that the tachinid, Euclytia flava (Townsend), exploits methyl (E,Z,Z)-2,4,6-decatrienoate as a kairomone. We also report the unexpected finding that various isomers of methyl 2,4,6-decatrienoate attract Acrosternum hilare (Say), although this bug apparently does not produce methyl decatrienoates. Other stink bugs and tachinids native to North America were also attracted to methyl 2,4,6-decatrienoates. These data indicate there are Heteroptera in North America in addition to Thyanta spp. that probably use methyl 2,4,6-decatrienoates as pheromones. The evidence that some pentatomids exploit the pheromones of other true bugs as kairomones to find food or to congregate as a passive defense against tachinid parasitism is discussed. PMID- 17334918 TI - Food wrapping with the postpharyngeal gland secretion by females of the European beewolf Philanthus triangulum. AB - Ground-nesting animals share their habitat with countless microorganisms that can play important roles as pathogens or competitors for food resources. Thus, species that store food in the soil, either for themselves or for their progeny, must protect these resources against microbial degradation. Females of the European beewolf, Philanthus triangulum, hunt honeybees as provisions for their brood and store the paralyzed prey in their subterranean nests. A previous study had shown that females lick the surface of prey before oviposition and that this licking treatment delays mold growth. Here, we showed that females apply large amounts of a secretion from their postpharyngeal glands onto the surface of their prey during the licking behavior. Inhibition-zone assays showed that comparatively large amounts of the gland secretion had no direct antimycotic effect. We discuss our findings with regard to other possible mechanisms of the postpharyngeal gland secretion against fungal growth. PMID- 17334919 TI - Response of the aphid parasitoid Aphidius funebris to volatiles from undamaged and aphid-infested Centaurea nigra. AB - Two issues have hindered the understanding of the ecology and evolution of volatile-mediated tritrophic interactions: few studies have addressed noncrop systems; and few statistical techniques have been applied that are suitable for the analysis of complex volatile blends. In this paper, we addressed both of these issues by studying the noncrop system involving the plant Centaurea nigra, the specialist aphid Uroleucon jaceae, and the parasitoid Aphidius funebris. In a Y-tube olfactometer, A. funebris was attracted to the odor from undamaged C. nigra, but preferred the plant-host complex (PHC) after 3 d of feeding by 200 U. jaceae over the undamaged plant, but not after three or 5 d of feeding by 50 U. jaceae. When aphids were removed, the initial preference for the damaged plant remained, but the final preference was not greater than for the undamaged plant. No qualitative differences were detected between the headspaces of C. nigra and the C. nigra-U. jaceae PHC. For quantitative analysis, we used a compositional approach, which treats each compound produced as part of a blend, and not as a compound released in isolation, thus allowing analysis of the relative contribution of each compound to the blend as a whole. With this approach, subtle increases and decreases of some green leaf volatiles and monoterpenoids on the third day of aphid infestation were detected. Mechanically damaged C. nigra had a volatile profile that differed from undamaged C. nigra and the PHC. One and 10 ng of (Z)-3-hexenyl acetate, and 10 or 100 ng of 6-methyl-5-hepten-2-one were attractive to the parasitoid when placed in solution on filter paper. A. funebris appears to be using a combination of chemical cues to locate host-infested plants. PMID- 17334920 TI - (11Z,13E)-Hexadecadien-1-yl acetate: sex pheromone of the grass webworm Herpetogramma licarsisalis-identification, synthesis, and field bioassays. AB - The grass webworm Herpetogramma licarsisalis (Lepidoptera: Crambidae), which has recently established in pasture in Northland, New Zealand, is an important pest of many tropical and subtropical grasses. Two pheromone components, (Z)-11 hexadecen-1-yl acetate (Z11-16:Ac) and (11Z,13E)-hexadecadien-1-yl acetate (Z11,E13-16:Ac), were identified in pheromone gland extracts of female moths by gas chromatography (GC), GC-electroantennographic detection, and GC-mass spectrometry in conjunction with microchemical tests (dimethyldisulfide and 4 methyl-1,2,4-triazoline-3,5-dione derivatizations). Z11,E13-16:Ac and its geometric isomer (11E,13Z)-hexadecadien-1-yl acetate (E11,Z13-16:Ac) were synthesized via stereoselective Wittig reactions, and the identity of the diene present in the pheromone glands was confirmed to be Z11,E13-16:Ac. Field bioassays at Indooroopilly in Brisbane, Australia, established that Z11,E13-16:Ac was necessary and sufficient for attraction of male grass webworm moths and that the corresponding alcohol, (11Z,13E)-hexadecadien-1-ol (Z11,E13-16:OH), had a strong inhibitory effect on trap catches at the ratios tested. When mixed with Z11,E13-16:Ac in various ratios, Z11-16:Ac had no effect on the attractiveness of lures. PMID- 17334921 TI - Inter- and intraspecific variation in floral scent in the genus salix and its implication for pollination. AB - The floral scent composition of 32 European and two Asian Salix L. species (Salicaceae) was analyzed. Intra- and interspecific variation was compared for a subset of 8 species. All Salix species are dioecious and floral scent was collected from both male and female individuals by using a dynamic headspace MicroSPE method, and analyzed by GC-MS. A total of 48 compounds were detected, most of them being isoprenoids and benzenoids. Commonly occurring compounds included trans-beta-ocimene, cis-beta-ocimene, benzaldehyde, D-limonene, alpha pinene, cis-3-hexenyl aceatate, linalool, 1,4-dimethoxybenzene, and beta-pinene. Two compounds, 1,4-dimethoxybenzene and trans-beta-ocimene, were responsible for most of the interspecific variation. In a subset of eight extensively sampled species, six had a characteristic floral scent composition; half of the pairwise species comparisons confirmed significant differences. In three of these eight species, intraspecific variability could be explained by sex differences. Variation in Salix floral scent may provide specific signals that guide pollinators and thus contribute to the reproductive isolation of compatible and cooccurring species. PMID- 17334922 TI - The distribution of two major Iridoids in different organs of Antirrhinum majus L. at selected stages of development. AB - Two iridoid glucosides isolated from leaves of Antirrhinum majus L. were identified as the known compounds antirrhinoside and antirrhide. Plants grown hydroponically demonstrated that antirrhinoside is present in all plant organs including the roots. In contrast, antirrhide is found only in leaves. Furthermore, both iridoids were identified in the main stem axillary leaves and leaves on the lateral branches. The highest concentrations of antirrhinoside were found in the main and lateral stems as well as the buds and flowers. As leaves age, for both cultivars, the levels of antirrhinoside drop significantly, and there is a corresponding increase in antirrhide. In spite of the different genetic backgrounds of the two cultivars, the overall distribution of the iridoids was similar during vegetative and flowering development. Radiolabeling of recently expanded axillary leaves with (14)CO(2) showed that both antirrhinoside and antirrhide were prominently labeled in the laminar tissue. However, only (14)C-antirrhinoside was recovered in the subtending petiole tissue, consistent with the suggestion that it is a phloem mobile compound. PMID- 17334923 TI - Jasmonic acid-induced changes in Brassica oleracea affect oviposition preference of two specialist herbivores. AB - Jasmonic acid (JA) is a key hormone involved in plant defense responses. The effect of JA treatment of cabbage plants on their acceptability for oviposition by two species of cabbage white butterflies, Pieris rapae and P. brassicae, was investigated. Both butterfly species laid fewer eggs on leaves of JA-treated plants compared to control plants. We show that this is due to processes in the plant after JA treatment rather than an effect of JA itself. The oviposition preference for control plants is adaptive, as development time from larval hatch until pupation of P. rapae caterpillars was longer on JA-treated plants. Total glucosinolate content in leaf surface extracts was similar for control and treated plants; however, two of the five glucosinolates were present in lower amounts in leaf surface extracts of JA-treated plants. When the butterflies were offered a choice between the purified glucosinolate fraction isolated from leaf surface extracts of JA-treated plants and that from control plants, they did not discriminate. Changes in leaf surface glucosinolate profile, therefore, do not seem to explain the change in oviposition preference of the butterflies after JA treatment, suggesting that as yet unknown infochemicals are involved. PMID- 17334924 TI - Estimating stage occupation probabilities in non-Markov models. AB - We study non-Markov multistage models under dependent censoring regarding estimation of stage occupation probabilities. The individual transition and censoring mechanisms are linked together through covariate processes that affect both the transition intensities and the censoring hazard for the corresponding subjects. In order to adjust for the dependent censoring, an additive hazard regression model is applied to the censoring times, and all observed counting and "at risk" processes are subsequently given an inverse probability of censoring weighted form. We examine the bias of the Datta-Satten and Aalen-Johansen estimators of stage occupation probability, and also consider the variability of these estimators by studying their estimated standard errors and mean squared errors. Results from different simulation studies of frailty models indicate that the Datta-Satten estimator is approximately unbiased, whereas the Aalen-Johansen estimator either under- or overestimates the stage occupation probability due to the dependent nature of the censoring process. However, in our simulations, the mean squared error of the latter estimator tends to be slightly smaller than that of the former estimator. Studies on development of nephropathy among diabetics and on blood platelet recovery among bone marrow transplant patients are used as demonstrations on how the two estimation methods work in practice. Our analyses show that the Datta-Satten estimator performs well in estimating stage occupation probability, but that the censoring mechanism has to be quite selective before a deviation from the Aalen-Johansen estimator is of practical importance. PMID- 17334925 TI - Nonparametric estimation of a regression function from backward recurrence times in a cross-sectional sampling. AB - This study considers the nonparametric estimation of a regression function when the response variable is the waiting time between two consecutive events of a stationary renewal process, and where this variable is not completely observed. In these circumstances, our data are the recurrence times from the occurrence of the last event up to a pre-established time, along with the corresponding values of a certain set of covariates. Estimation of the error density function and some of its characteristics are also considered. For the proposed estimators, we first analyze their asymptotic behavior and, thereafter, carry out a simulation study to highlight their behavior in finite samples. Finally, we apply this methodology to an illustrative example with biomedical data. PMID- 17334926 TI - Post partum discharge against medical advice: who leaves and does it matter? AB - OBJECTIVE: To examine risk factors and sequela for post partum discharge against medical advice. METHODS: We conducted cross-sectional analyses of hospital discharge data linked to American Hospital Association data for women discharged following a live birth for California, Florida, and New York in the years 1998 2000. We examined rates, risk factors, hospital readmission rate and mortality (California only), associated with discharge against medical advice after controlling for patient and hospital characteristics. RESULTS: Post partum discharge against medical advice averaged 0.10%. Rates were lowest among women following uncomplicated cesarean and vaginal births (0.07%), intermediate following complicated vaginal birth (0.21%) and highest following complicated cesarean birth (0.29%). African American race, lower income, public health insurance, no health insurance, or greater comorbidity, particularly drug abuse or psychotic illness, discharge from a hospital in California or New York (compared to Florida), and location in medium or large metropolitan areas, were associated with significantly higher rates of discharge against advice. Asian or Hispanic race or ethnicity and delivery at an obstetrical specialized hospital were associated with lower risk. Patients discharged against medical advice in California were significantly more likely to be re-admitted within 30 days (adjusted odds ratio 2.7; 95% confidence interval [CI] 1.8-3.9), though none died during the period. CONCLUSIONS: Discharge against medical advice among post partum patients is uncommon, but occurs primarily among vulnerable women with psychosocial and medical risk factors. Thus, discharge against medical advice may help identify women who may benefit from additional maternal and/or child services. PMID- 17334927 TI - MRI finding of simultaneous coexistence of growth hormone-secreting pituitary adenoma with intracranial meningioma and carotid artery aneurysms: report of a case. AB - Coexistence of pituitary adenoma, intracranial meningioma and cerebral aneurysm has never been described. We report on a patient with GH-secreting pituitary macroadenoma associated with a right frontal meningioma and with two intracavernous asymptomatic aneurisms. A 61-year-old woman was referred to our Endocrine Unit 13 years after a right frontal craniotomy for a pituitary tumour. Endocrine investigation showed high levels of IGF-1 (560 ng/ml) and increased basal serum GH (56 ng/ml) levels, not suppressed after OGTT. MRI showed persistence of a homogeneously enhancing intra- and suprasellar lesion, compressing the visual pathways, with bilateral intracavernous invasion and simultaneous coexistence of a right intracavernous internal carotid artery (ICA) aneurysm in direct contact with the pituitary tumour. Somatostatin analog treatment normalized GH and IGF-1 levels. Eight months later, the patient underwent a balloon ICA occlusion with disappearance of the right ICA aneurysm. One year later, a new MRI confirmed the presence of the pituitary mass showing also a right intracranial frontal meningioma and a new ICA aneurysm on the left side. Previous studies have suggested that prolonged GH hypersecretion could play a role in the genesis of intracranial aneurysms, inducing atherosclerotic and/or degenerative modification of the arterial walls. Other aetiological factors include a mechanical effect due to a direct contact between adenoma and aneurysm. Coexistence of pituitary adenoma and intracranial meningioma is a rare event, but also for this association it has been suggested that GH or other growth factors could play a role in appearance or in growth of meningioma. In our case, meningioma appeared and grew, despite the effective treatment of acromegaly. PMID- 17334928 TI - Human genetics of GPR54. AB - Idiopathic hypogonadotropic hypogonadism (IHH) is a condition characterized by absence of sexual maturation in the setting of low sex steroids and low/normal gonadotropins. Despite its rarity, considerable genetic heterogeneity and phenotypic variability exists in this disorder. Loss of function mutations in a G protein coupled receptor, GPR54, have been shown to cause IHH. Although mutations in GPR54 are not a common cause of this condition, patients bearing mutations are critical to explore genotype-phenotype correlations and gene function. In this review, we will examine the human genetics studies of GPR54, the phenotypic implications of mutations in this gene, and the emerging roles of the kisspeptin/GPR54 pathway. PMID- 17334929 TI - Kisspeptin expression in the brain: catalyst for the initiation of puberty. AB - In 2003, two independent groups of researchers discovered almost simultaneously that inactivating mutations of the G protein coupled receptor, GPR54, cause hypogonadotropic hypogonadism in mice and men. Since this discovery, kisspeptins, the natural ligands for GPR54, have been thrust into the reproductive neuroendocrine spotlight, as major regulators of GnRH function. Kisspeptins are the peptide products of the KiSS-1 gene, and potently stimulate gonadotrophin secretion when administered either centrally or peripherally. Expression of KiSS 1 has been localised to specific regions of the hypothalamus in many species and is regulated by gonadal steroids and across the estrous cycle. It appears that kisspeptin transmits steroid feedback signals to GnRH cells, especially the positive feedback effect of estrogen that causes the preovulatory GnRH/LH surge. Importantly, kisspeptin function appears to be fundamental to the initiation of puberty. PMID- 17334931 TI - Effect of age-at-release on long term sexual re-offense rates in civilly committed sexual offenders. AB - A cohort of 136 rapists and 115 child molesters civilly committed to a prison in Massachusetts and followed for 25 years (see Prentky, Lee, Knight, & Cerce, 1997) was examined for the effect of age at time of release on sexual recidivism. The present study (1) examined the recidivism rates for each of five age-at-release groups, separately for rapists and child molesters, (2) tested the fit of linear and quadratic models for 5, 10, 15, 20, and 25-year windows using Cox regression analysis, (3) presented the predicted failure rates for rapists (up to five years post-release) and child molesters (out 21 years post-release), and (4) provided a computational formula for estimating the sexual recidivism rate given an individual's age and number of years post-release. For rapists, a linear model extending 5 years best captured our data (LR=5.62, p<.02). Going out any further than 5 years did not enhance the predictive efficacy of the model. By contrast, a quadratic model extending the full duration of the study (25 years) provided the best fit (LR=6.30, p<.04) for child molesters. Our data supported the general conclusion that risk of sexual recidivism diminishes as a function of increasing age at time of release for rapists. We found marked differences, however, in the re-offense patterns of rapists and child molesters, with the latter group evidencing a distinct quadratic, rather than linear, pattern. Since these findings derive from a population screened for civil commitment by virtue of their presumptive dangerousness, they may not be generalizable to samples of sex offenders drawn from the general prison population. PMID- 17334932 TI - Community-based treatment of venous thromboembolism with a low-molecular-weight heparin and warfarin. AB - This multicenter, prospective, open label, observational study evaluated practice patterns of physicians using tinzaparin, a low-molecular-weight heparin (LMWH), and warfarin for the treatment of deep venous thrombosis (DVT) with or without pulmonary embolism (PE). Short-term recurrence of venous thromboembolism (VTE) and safety were also evaluated. Patients with an objective diagnosis of DVT, with or without PE, were invited by their physician to participate in this study. Treatment was given according to the approved U.S. package inserts for tinzaparin (175 IU/kg SQ QD) and warfarin and the clinical judgment of the prescribing physician. Baseline patient history including demographic information and the results of tests to confirm the diagnosis of DVT, with or without PE, were collected. Follow-up information included the treatment setting in which each dose of tinzaparin was administered, medical training of the person administering tinzaparin doses, timing of initiation of warfarin with respect to that of tinzaparin, length of overlap of tinzaparin and warfarin therapy, and adverse experiences. A total of 334 patients were enrolled at 65 sites. Patients across a wide age (range 18-93 years old) and body weight (range 40-261 kg) were included. Overall, 27.3% of patients had cancer, and 50% of the overall study population reported more than one VTE risk factor. Mean duration of tinzaparin treatment was 7.61 days. Therapy at home was more common in suburban and rural settings than in urban settings. High proportions of patient, even among the small group with concurrent PE, were treated at home with self-injection. Severity of disease was the primary reason for hospitalization. Home treatment of DVT, with or without PE, with self administration of tinzaparin at 175 IU SQ once-daily was safe and resulted in an acceptably low rate of recurrent venous thromboembolism and adverse events. Home therapy in the usual practice setting should achieve substantial overall cost savings in the treatment of DVT. PMID- 17334933 TI - G20210A Prothrombin gene variant in Turkish patients with angiographically documented coronary artery disease. AB - BACKGROUND: G-->A substitution at position 20210A in the 3'-untranslated region in prothrombin gene is associated with raised plasma prothrombin. G20210A prothrombin variant has been associated with high prothrombin levels and an increased risk of venous thrombosis. To determine the prevalence of the G20210A prothrombin variant among Turkish and to evaluate the potential relevance of this variant to Turkish patients with angiographically documented coronary artery disease (CAD). METHODS: We conducted a case-control study on 268 unrelated subjects who referred to the cardiology department of the university hospital for coronary angiography. One hundred-thirty seven patients with angiographically documented CAD and 131 subjects without angiographically documented CAD were studied to examine the association of the G20210A prothrombin variant with CAD. Blood samples from the patients and controls were analyzed for the G20210A prothrombin variant by DNA analysis, using polimeraz chain reaction. RESULTS: G20210A prothrombin variant was found in 6 of 137 (4.4%) patients with CAD and 1 of 131 (0.8%) in control subjects (p = 0.064). There were no significant differences in terms of diabetes mellitus, hypertension, dyslipidemia, sex and family history of CAD with and without the G20210A prothrombin variant in the patient group. CONCLUSIONS: In agreement with the results of recent meta analyses, our data from northeast Anatolia show a 5-fold higher prevalence of the G20210A prothrombin variant among the patients with angiographically-documented CAD when compared with those without angiographic signs of significant CAD and its variant cannot be considered as a risk factor for CAD in this region. PMID- 17334934 TI - Inhibition of thrombin activity by prothrombin activation fragment 1.2. AB - Prothrombin is the precursor of thrombin, the central enzyme in coagulation. Prothrombin is activated in vivo by the prothrombinase complex to form fragment 1.2 and thrombin. Fragment 1.2 has an amino-terminal gla domain and two kringle domains. The second kringle domain (kringle 2) binds to the exosite II on thrombin. Nascent thrombin generated on platelet surface remains non-covalently bound to fragment 1.2 by kringle 2-exosite II interaction. To determine whether this interaction can modulate coagulant activity of thrombin, we labeled thrombin at the active site with fluorescein-Phe-Pro-Arg chloromethylketone and monitored the fluorescence changes upon ligand binding. Anionic phospholipid-bound fragment 1.2 and fragment 2 bound to FPR-thrombin and induced changes in the active site with half maximal effects at 7.2 microM and 8.8 microM, respectively. We also tested the effect of anionic phospholipid-bound fragment 1.2 (0-10 microM) on thrombin clotting activity. Phospholipid-bound fragment 1.2 inhibited fibrinogen clotting in a concentration-dependent manner but had no significant effect on amidolytic activity towards S2238, suggesting a competitive inhibition of the fibrinogen binding site. Furthermore, fragment 1.2 inhibited FPR-thrombin binding to platelet. Consistent with these findings fragment 1.2 inhibited thrombin induced aggregation of gel filtered platelets in a concentration-dependant manner. These results suggest that the membrane-bound prothrombin fragment 1.2 may play a role in hemostasis by down regulating the procoagulant activity of newly formed thrombin. PMID- 17334936 TI - Community engagement in urban health research. PMID- 17334935 TI - Routine upstream versus selective down stream use of tirofiban in non-ST elevation myocardial infarction patients scheduled for early invasive therapy; a randomized comparison. AB - BACKGROUND: Despite their proven beneficial effects and inclusion in the guidelines, glycoprotein (GP) IIb/IIIA blockers are underused in daily practice in patients with non ST-segment elevation acute coronary syndrome (NSTE ACS). This study combines the data from two randomized controlled trials, comparing routine upstream versus selective down stream use of tirofiban in patients with NSTE ACS. METHODS: Inclusion criteria for both studies (ELISA-1 and 2) were angina pectoris, with ST depression >1 mm and or a positive cardiac biomarkers. All patients were scheduled for coronary angiography. The primary and secondary end points for both studies were enzymatic infarct size (LDHQ48) and initial TIMI flow of the culprit lesion respectively. RESULTS: From August 2000 to January 2005, 273 patients were randomized to routine upstream tirofiban and 275 patients to selective down stream use of tirofiban. Selective down stream tirofiban was used in 55 patients (20%). Patients in the upstream group more often had a patent culprit lesion (65% vs. 50%, P=0.003) and a significantly smaller enzymatic infarct size, LDHQ48 median (25-75%): 125 (55-309) vs. 189 (68-504) IU/l, P=0.006 as compared to the selective down stream group. Subgroup analysis showed that routine upstream tirofiban was particularly effective in males, patients with a positive troponin on admission and in those not pretreated with clopidogrel. CONCLUSION: Routine upstream GP IIb/IIIa is mainly effective in patients with elevated troponin on admission and those not pretreated with clopidogrel. Large scale randomized trials are needed to evaluate the effect of GP IIb/IIIa blockers on top of clopidogrel pretreatment on major adverse cardiac events. PMID- 17334938 TI - Observed patterns of illicit opiate overdose deaths in Chicago, 1999-2003. AB - This article explores trends and correlates of Chicago's opiate-related overdose (OD) deaths. We manually examined data from every death certificate filed between 1999 and 2003 to identify all Chicago residents' accidental deaths involving acute intoxication with illicit opiates, OD, or opiate poisoning. The analysis includes an examination of contextual characteristics in 77 Chicago neighborhoods. Negative binomial regression analysis permits the calculation of incidence rate ratios (IRR) associated with time trends. OD incidence peaked in 2000 and then declined markedly by 2003 [year 2000-2003 IRR = 0.65, 95% confidence interval (CI) (0.54, 0.78)]. Over the 2000-2003 period, overall incidence of fatal OD declined by 34%. Over this period, the sharpest observed declines occurred among African-Americans [IRR = 0.64, 95% CI (0.51, 0.81)] and Hispanics/Latinos [IRR = 0.53, 95% CI (0.32, 0.88)]. The opiate-related fatality incidence also declined among non-Hispanic whites [IRR = 0.743, 95% CI (0.52, 1.06)]. Even at the end of the study period, illicit opiate-related OD accounted for 35% of all accidental deaths to Chicago adults aged 18-64, with 45% of OD deaths occurring among African-American men. In summary, illicit opiate OD in Chicago peaked in 2000 and markedly declined by 2003. Opiate OD continues to pose a major threat of mortality to Chicago adults. PMID- 17334940 TI - Emotional support and affect: associations with health behaviors and active coping efforts in men living with HIV. AB - The present study represents a cross-sectional examination of the relationship between affect, social support and illness adjustment in men diagnosed with HIV/AIDS. Positive and negative affect were examined as separate mediators of the relationship between emotional support received from a primary support provider and illness adjustment in 105 men living with HIV. Results suggested that depressive symptoms emerged as a mediator between emotional support and engaging in healthy lifestyle behaviors (assessed by summary index). In contrast, positive affect emerged as the primary mediator between emotional support and greater amounts of active coping. Overall, findings suggested that emotional support from close others was indirectly associated with health behaviors and coping through recipients' affective states, and that these positive and negative affective states had differential relationships with multiple aspects of illness adjustment in men living with HIV. PMID- 17334939 TI - The effect of a case management intervention on drug treatment entry among treatment-seeking injection drug users with and without comorbid antisocial personality disorder. AB - We examined the effect of a case management intervention on drug treatment entry among injection drug users (IDUs) with and without comorbid antisocial personality disorder (ASPD). Injection drug users attending the Baltimore Needle Exchange Program who sought and were granted referrals to opioid agonist treatment were randomized to receive a strengths-based case management intervention or passive referral. Of 162 IDUs, 22.8% met the DSM-IV criteria for ASPD. Compared to those without ASPD, IDUs with comorbid ASPD who spent 25 or more minutes with their case manager prior to their treatment entry date were 3.51 times more likely to enter treatment than those receiving less than 5 min, adjusting for intervention status, race, and treatment site (95% confidence interval 1.04-11.89). Providing case management services to IDUs with comorbid ASPD may facilitate treatment entry and reduce the negative consequences of drug abuse. PMID- 17334942 TI - Using a human cardiopulmonary model to study and predict normal and diseased ventricular mechanics, septal interaction, and atrio-ventricular blood flow patterns. AB - We upgraded our human cardiopulmonary (CP) model with additional data that enables it to more accurately simulate normal physiology. We then tested its ability to explain human disease by changing two parameter values that decrease ventricular compliance, and found that it could predict many of the hemodynamic, gas exchange, and autonomic abnormalities found in patients with left ventricular diastolic dysfunction (LVDD). The newly incorporated information includes high fidelity pressure tracings simultaneously recorded from the RV and LV of a normal human in a cardiac catheterization laboratory, Doppler echocardiographic inlet flow velocity patterns, measures of right and left ventricular impedance, and atrial volumes. The revised cardiovascular section details the hemodynamics of a normal subject to the extent that it can now explain the effects of septal compliance on ventricular interaction, the differences in left and right ventricular pressure development, and venous blood gas mixing in the right atrium. The model can isolate the highly interrelated features of normal and abnormal physiology, and simultaneously demonstrate their interaction in a manner that would be very difficult or impossible using an intact organism. It may therefore help physicians and scientists understand, diagnose, and improve their treatment of complicated cardiovascular and pulmonary diseases. It could also simulate the hemodynamic and respiratory effects of ventricular and pulmonary assist devices, and thus help with their development. PMID- 17334941 TI - Differentiation restricted endocytosis of cell penetrating peptides in MDCK cells corresponds with activities of Rho-GTPases. AB - PURPOSE: Cellular entry of biomacromolecules is restricted by the barrier function of cell membranes. Tethering such molecules to cell penetrating peptides (CPPs) that can translocate cell membranes has opened new horizons in biomedical research. Here, we investigate the cellular internalization of hCT(9-32)-br, a human calcitonin derived branched CPP, and SAP, a gamma-zein related sequence. METHODS: Internalization of fluorescence labelled CPPs was performed with both proliferating and confluent MDCK cells by means of confocal laser scanning microscopy (CLSM) and fluorescence activated cell sorting (FACS) using appropriate controls. Internalization was further elaborated in an inflammatory, IFN-gamma/TNF-alphaa induced confluent MDCK model mimicking inflammatory epithelial pathologies. Activities of active form Rho-GTPases (Rho-A and Rac-1) in proliferating and confluent MDCK cells were monitored by pull-down assay and Western blot analysis. RESULTS: We observed marked endocytic uptake of the peptides into proliferating MDCK by a process suggesting both lipid rafts and clathrin-coated pits. In confluent MDCK, however, we noted a massive but compound unspecific slow-down of endocytosis. This corresponded with a down-regulation of endocytosis by Rho-GTPases, previously identified to be intimately involved in endocytic traffic. In fact, we found endocytic internalization to relate with active Rho-A; vice versa, MDCK cell density, degree of cellular differentiation and endocytic slow-down were found to relate with active Rac-1. To our knowledge, this is the first study to cast light on the previously observed differentiation restricted internalization of CPPs into epithelial cell models. In the inflammatory IFN-gamma/TNF-alphaa induced confluent MDCK model mimicking inflammatory epithelial pathologies, CPP internalization was enhanced in a cytokine concentration-dependent way resulting in maximum enhancement rates of up to 90%. We suggest a cytokine induced redistribution of lipid rafts in confluent MDCK to cause this enhancement. CONCLUSION: Our findings emphasize the significance of differentiated cell models in the study of CPP internalization and point towards inflammatory epithelial pathologies as potential niche for the application of CPPs for cellular delivery. PMID- 17334944 TI - Efficacy of Lagenidium giganteum metabolites on mosquito larvae with reference to nontarget organisms. AB - Lagenidium giganteum is a water mold and an effective mosquito control agent with limited use due to poor survival and contamination during storage. Invert extracellular metabolites of L. giganteum is easy to produce, long shelf life, and a potential candidate in tropical climates. This fungus was grown in PYG broth in the laboratory at 25 +/- 2 degrees C, and relative humidity was maintained at 75 +/- 5% for 15 +/- 2 days. Filtration process of metabolites was done using Whatman filter paper, column chromatograph, and range syringe filters techniques. Then 5-ml fractions were collected and used to assay larvicidal efficacies. Larvicidal efficacies were performed against Culex quinquefasciatus, Anopheles stephensi, and Aedes aegypti at five different concentrations, viz. 1.68, 1.99, 2.17, 2.30, and 2.40 ppm. And also, filtrates were assessed against four species of nontarget organisms named Daphnia pulex, Cyclopes, Lymnea auriculeta, and tadpoles of Rana tigrina with different concentrations. The mortality values were subjected by the Probit analysis. The complete mortalities that resulted from applying filtrates dosage on all instars of mosquitoes persisted for a period of 24, 48, and 72 h, respectively. The efficacies in killing instar of three important vectors and safer for nontarget organisms with good biological stability of extracellular metabolites make this a promising alternative to mycelium and conidial-based larvicides. It could be regarded as fungal-based natural larvicide for the use of vector control. PMID- 17334943 TI - Thyroid hormones reorganize the cytoskeleton of glial cells through Gfap phosphorylation and Rhoa-dependent mechanisms. AB - Thyroid hormones (3,5,3'-triiodo-L: -thyronine, T3; 3,5,3',5'-L: tetraiodothyronine, T4; TH) play crucial roles in the growth and differentiation of the central nervous system. In this study, we investigated the actions of TH on proliferation, viability, cell morphology, in vitro phosphorylation of glial fibrillary acidic protein (GFAP) and actin reorganization in C6 glioma cells. We first observe that long-term exposure to TH stimulates cell proliferation without induce cell death. We also demonstrate that after 3, 6, 12, 18, and 24 h treatment with TH, C6 cells and cortical astrocytes show a process-bearing shape. Furthermore, immunocytochemistry with anti-actin and anti-GFAP antibodies reveals that TH induces reorganization of actin and GFAP cytoskeleton. We also observe an increased in vitro 32P incorporation into GFAP recovered into the high-salt Triton insoluble cytoskeletal fraction after 3 and 24 h exposure to 5 x 10(-8) and 10(-6) M T3, and only after 24 h exposure to 10(-9) M T4. These results show a T3 action on the phosphorylating system associated to GFAP and suggest a T3 independent effect of T4 on this cytoskeletal protein. In addition, C6 cells and astrocytes treated with lysophosphatidic acid, an upstream activator of the RhoA GTPase pathway, totally prevented the morphological alterations induced by TH, indicating that this effect could be mediated by the RhoA signaling pathway. Considering that IF network can be regulated by phosphorylation leading to reorganization of IF filamentous structure and that alterations of the microfilament organization may have important implications in glial functions, the effects of TH on glial cell cytoskeleton could be implicated in essential neural events such as brain development. PMID- 17334945 TI - Gene expression analysis in LLC-PK1 renal tubular cells by atrial natriuretic peptide (ANP): correlation of homologous human genes with renal response. AB - We used human DNA microarray to explore the differential gene expression profiling of atrial natriuretic peptide (ANP)-stimulated renal tubular epithelial kidney cells (LLC-PK1) in order to understand the biological effect of ANP on renal kidney cell's response. Gene expression profiling revealed 807 differentially expressed genes, consisting of 483 up-regulated and 324 down regulated genes. The bioinformatics tool was used to gain a better understanding of differentially expressed genes in porcine genome homologous with human genome and to search the gene ontology and category classification, such as cellular component, molecular function and biological process. Four up-regulated genes of ATP1B1, H3F3A, ITGB1 and RHO that were typically validated by real-time quantitative PCR (RT-qPCR) analysis serve important roles in the alleviation of renal hypertrophy as well as other related effects. Therefore, the human array can be used for gene expression analysis in pig kidney cells and we believe that our findings of differentially expressed genes served as genetic markers and biological functions can lead to a better understanding of ANP action on the renal protective system and may be used for further therapeutic application. PMID- 17334946 TI - Complete genome sequence supports bell pepper mottle virus as a species of the genus Tobamovirus. AB - Biological properties and the complete genome sequence of bell pepper mottle virus (BPeMV) were determined. The full genome of BPeMV consists of 6375 nucleotides. The BPeMV genomic RNA has four open reading frames (ORFs) encoding proteins of M(r) 126, 181, 30 and 18 kDa from the 5' to the 3' end, respectively. The lengths of the 5' nontranslated region (NTR) and the 3' NTR are 71 and 198 nucleotides, respectively. Overall identities for the four ORFs of BpeMV, at the nucleotide and amino acid levels, respectively, ranged from 36.0 to 80.6% and from 32.1 to 90.9%, compared to those of 22 other tobamoviruses. The CP gene of BPeMV displayed 43.5-73.5% and 32.1-82.4% identity to those of 22 other tobamoviruses at the nucleotide and amino acid levels, respectively. Phylogenetic analyses of four viral proteins clearly supported the conclusion that BPeMV encoded proteins were related to those of members of the Solanaceae-infecting tobamoviruses. BPeMV was closely related to tomato mosaic virus, and tobacco mosaic virus and different from other tobamoviruses. Western blot analysis showed that BPeMV cross-reacted strongly with antibodies against members of Solanaceae infecting tobamoviruses. These data represent the first molecular evidence supporting BPeMV as a separate species of the genus Tobamovirus. PMID- 17334947 TI - Making a friend from a foe: expressing a GroEL gene from the whitefly Bemisia tabaci in the phloem of tomato plants confers resistance to tomato yellow leaf curl virus. AB - Some (perhaps all) plant viruses transmitted in a circulative manner by their insect vectors avoid destruction in the haemolymph by interacting with GroEL homologues, ensuring transmission. We have previously shown that the phloem limited begomovirus tomato yellow leaf curl virus (TYLCV) interacts in vivo and in vitro with GroEL produced by the whitefly vector Bemisia tabaci. In this study, we have exploited this phenomenon to generate transgenic tomato plants expressing the whitefly GroEL in their phloem. We postulated that following inoculation, TYLCV particles will be trapped by GroEL in the plant phloem, thereby inhibiting virus replication and movement, thereby rendering the plants resistant. A whitefly GroEL gene was cloned in an Agrobacterium vector under the control of an Arabidopsis phloem-specific promoter, which was used to transform two tomato genotypes. During three consecutive generations, plants expressing GroEL exhibited mild or no disease symptoms upon whitefly-mediated inoculation of TYLCV. In vitro assays indicated that the sap of resistant plants contained GroEL TYLCV complexes. Infected resistant plants served as virus source for whitefly mediated transmission as effectively as infected non-transgenic tomato. Non transgenic susceptible tomato plants grafted on resistant GroEL-transgenic scions remained susceptible, although GroEL translocated into the grafted plant and GroEL-TYLCV complexes were detected in the grafted tissues. PMID- 17334948 TI - Characterization of cleavage sites and protease activity in the polyprotein precursor of Japanese marine aquabirnavirus and expression analysis of generated proteins by a VP4 protease activity in four distinct cell lines. AB - A polyprotein precursor NH(2)-pVP2-VP4-VP3-COOH is encoded in genomic segment A of members of the family Birnaviridae. By N-terminal sequencing analysis, primary cleavage sites of a marine birnavirus (MABV) polyprotein were identified as Ala(508) downward arrow Ser(509) and Ala(734) downward arrow Ser(735), where the cleavage motif was the same as that of infectious pancreatic necrosis virus (IPNV). However, further VP4 and VP3 cleavages occurred at novel sites. Ser(633) and Lys(674) mutations affected the cleavage activity by site-directed mutagenesis. Additional catalytic residues including Ile(543) and Val(686) were MABV-specific. As shown by electron microscopy, pVP2 and further cleaved VP3s (fcVP3s) could not form virus-like particles (VLPs). This suggests that VP3 is necessary for VLP formation. By Western blot analysis of the VP3 expression, fcVP3s were found in RSBK-2 cells and FHM cells, while VP3 was cleaved less in EPC cells, suggesting that fcVP3s might merely be a degraded form. Alternatively, if fcVP3s play functional roles other than in viral assembly, the further VP3 cleavage is, at least, not restricted in FHM cells. Strangely, VP3 was not completely further cleaved in CHSE-214 cells despite the fact that this cell line has a potential proteolytic factor, implying that complicated factors are associated with the further VP3 cleavage. PMID- 17334949 TI - Molecular and antigenic characterization of rabbit hemorrhagic disease virus isolated in Cuba indicates a distinct antigenic subtype. AB - Phylogenetic analyses conducted on isolates of rabbit hemorrhagic disease virus (RHDV) from throughout the world have shown well-defined genogroups comprising representative strains of the virus and antigenic variants. In this work, we have isolated and characterized RHDV from the major epizootic that occurred in Cuba in 2004-2005. Sequence analysis of the capsid protein gene and antigenic characterization of this strain has allowed its inclusion as a member of the distinct RHDVa subtype. We also found that specific antibodies directed against RHDV reference strains bound to the Cuban isolate in a competition ELISA and inhibited virus hemagglutination in vitro. This is the second report on the molecular characterization of RHDVa circulating in the American region. PMID- 17334950 TI - Mitotic regulation of the anaphase-promoting complex. AB - Orderly progression through mitosis is regulated by the anaphase-promoting complex/cyclosome (APC/C), a large multiprotein E3 ubiquitin ligase that targets key mitotic regulators for destruction by the proteasome. APC/C has two activating subunits, Cdc20 and Cdh1. The well-established view is that Cdc20 activates APC/C from the onset of mitosis through the metaphase-anaphase transition, and that Cdh1 does so from anaphase through G1. Recent work, however, indicates that Cdh1 also activates APC/C in early mitosis and that this APC/C pool targets the anaphase inhibitor securin. To prevent premature degradation of securin, the nuclear transport factors Nup98 and Rae1 associate with APC/C(Cdh1) securin complexes. In late metaphase, when all kinetochores are attached to spindle microtubules and the spindle assembly checkpoint is satisfied, Nup98 and Rae1 are released from these complexes, thereby allowing for prompt ubiquitination of securin by APC/C(Cdh1). This, and other mechanisms by which the catalytic activity of APC/C is tightly regulated to ensure proper timing of degradation of each of its mitotic substrates, are highlighted. PMID- 17334951 TI - Tremor reduction by subthalamic nucleus stimulation and medication in advanced Parkinson's disease. AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor in Parkinson's disease (PD). Most of the recent studies used only clinical data to analyse tremor reduction. The objective of our study was to quantify tremor reduction by STN DBS and antiparkinsonian medication in elderly PD patients using an objective measuring system. Amplitude and frequency of resting tremor and re-emergent resting tremor during postural tasks were analysed using an ultrasound-based measuring system and surface electromyography. In a prospective study design nine patients with advanced PD were examined preoperatively off and on medication, and twice postoperatively during four treatment conditions: off treatment, on STN DBS, on medication, and on STN DBS plus medication. While both STN DBS and medication reduced tremor amplitude, STN DBS alone and the combination of medication and STN DBS were significantly superior to pre- and postoperative medication. STN DBS but not medication increased tremor frequency, and off treatment tremor frequency was significantly reduced postoperatively compared to baseline. These findings demonstrate that STN DBS is highly effective in elderly patients with advanced PD and moderate preoperative tremor reduction by medication. Thus, with regard to the advanced impact on the other parkinsonian symptoms, STN DBS can replace thalamic stimulation in this cohort of patients. Nevertheless, medication was still effective postoperatively and may act synergistically. The significantly superior efficacy of STN DBS on tremor amplitude and its impact on tremor frequency in contrast to medication might be explained by the influence of STN DBS on additional neural circuits independent from dopaminergic neurotransmission. PMID- 17334952 TI - Low awareness of transient ischemic attacks and risk factors of stroke in a Swiss urban community. AB - BACKGROUND AND PURPOSE: Time delays from stroke onset to arrival at the hospital are the main obstacles for widespread use of thrombolysis. In order to decrease the delays, educational campaigns try to inform the general public how to act optimally in case of stroke. To determine the content of such a campaign, we assessed the stroke knowledge in our population. METHODS: The stroke knowledge was studied by means of a closed-ended questionnaire. 422 randomly chosen inhabitants of Bern, Switzerland, were interviewed. RESULTS: The knowledge of stroke warning signs (WS) was classified as good in 64.7%. A good knowledge of stroke risk factors (RF) was noted in 6.4%. 4.2% knew both the WS and the RF of stroke indicating a very good global knowledge of stroke. Only 8.3% recognized TIA as symptoms of stroke resolving within 24 hours, and only 2.8% identified TIA as a disease requiring immediate medical help. In multivariate analysis being a woman, advancing age, and having an afflicted relative were associated with a good knowledge of WS (p = 0.048, p < 0.001 and p = 0.043). Good knowledge of RF was related to university education (p < 0.001). The good knowledge of TIA did not depend on age, sex, level of education or having an afflicted relative. CONCLUSIONS: The study brings to light relevant deficits of stroke knowledge in our population. A small number of participants could recognize TIA as stroke related symptoms resolving completely within 24 hours. Only a third of the surveyed persons would seek immediate medical help in case of TIA. The information obtained will be used in the development of future educational campaigns. PMID- 17334953 TI - 18F-FP-CIT PET imaging and SPM analysis of dopamine transporters in Parkinson's disease in various Hoehn & Yahr stages. AB - To investigate the usefulness of 18F-FP-CIT PET for assessing the severity of Parkinson's disease (PD) at various clinical stages, 41 patients with PD were divided into early (Hoehn&Yahr I-II, n = 23) and advanced (Hoehn & Yahr III-IV, n = 18) subgroups. 18F-FP-CIT PET was performed in these patients and 12 normal subjects. 18F-FP-CIT uptake in striatal subregions and its correlation with UPDRS were first evaluated by ROI analysis, and between-group differences were also analyzed by Statistical Parametric Mapping (SPM). Our results showed that striatal 18F-FP-CIT binding were significantly reduced to 70.9% (caudate), 46.8% (anterior putamen) and 24.0% (posterior putamen) in early PD compared with that of the control, and to 52.0%, 34.5% and 16.5% correspondingly in advanced PD, respectively. There was significant negative correlation between total motor UPDRS score of all parkinsonian patients and 18F-FP-CIT uptake in caudate nucleus (r = -0.53, p < 0.001), anterior putamen (r = -0.53, p < 0.001) and posterior putamen (r = -0.61, p < 0.001). SPM comparison of 18F-FP-CIT uptake between early or advanced PD and the control group showed significant decline in striatum, predominantly localized on the contralateral side and in the dorsal-posterior putamen. These results indicate that 18F-FP-CIT PET can serve as a suitable biomarker to represent the severity of PD in early and advanced stages. PMID- 17334954 TI - Quantitative measurement of trunk rigidity in parkinsonian patients. AB - We aimed to develop an objective measurement to quantify trunk rigidity in patients with Parkinson's disease (PD), and to examine its reliability, validity and sensitivity in differentiating PD patients from control subjects. In Study 1, an isokinetic dynamometer was employed to assess trunk rigidity in 6 PD patients and 6 healthy controls. Passive trunk flexion and extension at 4 angular velocities were applied and resistive torques were recorded. Both work done and resistive peak torques to passive trunk flexion (Torque(PF)) and extension (Torque(PE)) were found to be highly reliable within a 2-day interval in PD patients and control subjects. In Study 2, trunk muscle tone was compared between 15 PD and 15 control subjects. Significantly higher muscle tone, as shown by increases in work done, and in Torque(PF) and Torque(PE )at higher movement speeds, was found in PD patients. Within each subject group, resistive trunk muscle tone was found to increase with increasing velocity of passive movement, but the extent of increase was greater in PD patients. Our results thus suggest that the objective method developed by us was reliable and could differentiate trunk rigidity in PD patients from that of healthy subjects. PMID- 17334955 TI - Autonomic neuropathy in mixed cryoglobulinemia. AB - A retrospective, cross-sectional study was performed on a series of HCV-related mixed cryoglobulinemia (HCV-MC) patients to assess autonomic neuropathy (AN) and its relation to peripheral neuropathy (PN). Thirty consecutive patients affected by HCV-MC underwent clinical, neurological and electrodiagnostic examinations. Autonomic nervous system (ANS) involvement was assessed by functional cardiovascular tests and sympathetic skin response (SSR) evaluation. Sural nerve biopsy was performed in 10 patients with PN. All patients received steroids, 15 also received recombinant interferon-alpha2b (RIfn-alpha2b). PN occurred in 27 patients (90.0%) and AN in 4 (13.3 %) all with signs of PN. SSR was the autonomic test more frequently altered. Biopsy disclosed axonal degeneration more evident in the 4 patients with AN. Three out of 4 patients with AN received steroids and rIFN-alpha2b and 1 steroids alone. In our study on HCV-MC, it was concluded that AN can occur also without dysautonomic symptoms, SSR appears to be one of the optional tests to use together with dysautonomic tests to identify AN and finally PN and AN do not seem to be positively influenced by addition of rIFN-alpha2b to steroid treatment. PMID- 17334956 TI - A prospective study of physiotherapist prescribed community based exercise in inflammatory peripheral neuropathy. AB - There is insufficient evidence to support the use of exercise in the management of chronic disablement in people with inflammatory peripheral neuropathy. Therefore, our study aimed to determine the feasibility and effectiveness of a physiotherapist prescribed community based exercise programme for reducing chronic disablement in patients with stable motor neuropathy. We assessed the effects of a 12 week unsupervised, community based strengthening, aerobic and functional exercise programme on activity limitation and other measures of functioning in 16 people with stable motor neuropathy and 10 healthy control subjects. Fourteen of 16 patients and 8 out of 10 healthy control subjects completed the study and exercised safely in the community with no adverse events. Significant improvements were seen in all measures of activity limitation and in wider measures of health including anxiety, depression and fatigue in the patient group. Improvements were sustained at six months after completion of the exercise programme, except for depression. Ten patients continued to exercise regularly at six months. These findings demonstrate that individually prescribed community based exercise is feasible and acceptable for people with stable motor neuropathy and participation in exercise may be successful in reducing chronic disablement. Future randomised controlled trials are needed to examine the efficacy of this complex community based intervention. PMID- 17334957 TI - Patient preference in migraine therapy. A randomized, open-label, crossover clinical trial of acute treatment of migraine with oral almotriptan and rizatriptan. AB - OBJECTIVE: To assess patient preference for almotriptan 12.5 mg vs rizatriptan 10 mg for the acute treatment of migraine. METHODS: Randomized, multicenter, open label, crossover trial in which triptan-naive patients treated two moderate/severe migraine attacks, the first with one triptan and the second with the other: 183 patients took rizatriptan followed by almotriptan and 189 treated in the reverse order. Patient preference was assessed with a self-administered questionnaire. RESULTS: Of those recording a preference (209), 54.5% preferred almotriptan, but statistical significance was not achieved. The main reason for preference for one or the other triptan was efficacy: 43% of patients preferring almotriptan gave faster headache relief as the reason and 34% cited faster return to normal activities. The corresponding values for rizatriptan were 47% and 38%. A significantly greater proportion of those preferring almotriptan cited fewer adverse events (AEs) as the reason. Almotriptan and rizatriptan were of comparable efficacy and both treatments were well tolerated; 9% of patients experienced AEs probably or possibly related to study medication after almotriptan vs 14% after rizatriptan. Almotriptan was associated with a significantly lower incidence of triptan-associated AEs in triptan-naive patients (8.5% vs 18% with rizatriptan). CONCLUSION: Physicians should use information from meta-analyses and preference studies like this one to aid in the selection of a triptan with a high likelihood of providing rapid, sustained relief from pain coupled with an absence of AEs. About 55% of patients recording a preference in this trial preferred almotriptan, perhaps because of its combination of good efficacy and lower incidence of triptan-associated AEs. PMID- 17334958 TI - Acute motor axonal neuropathy presenting with bowel, bladder, and erectile dysfunction. PMID- 17334959 TI - Dissection of the internal carotid artery mimicking episodic cluster headache. PMID- 17334960 TI - Leber's hereditary optic neuropathy associated with cocaine, ecstasy and telithromycin consumption. PMID- 17334961 TI - Warm-up phenomenon in myotonia associated with the V445M sodium channel mutation. PMID- 17334962 TI - Nasal meningoencephalocele, an unusual cause for recurrent meningitis. Case report and review of the literature. PMID- 17334963 TI - Mikhail B. Kroll (1879-1939). PMID- 17334966 TI - CD83: an update on functions and prospects of the maturation marker of dendritic cells. AB - CD83 is one of the most characteristic cell surface markers for fully matured dendritic cells (DCs). In their function as antigen presenting cells they induce T-cell mediated immune responses. In this review we provide an overview on well described and proposed functions of this molecule as well as on very recent insights and new hypothesis. Already the CD83 messenger RNA processing differs remarkably from the processing of other cellular mRNAs: instead of the usual TAP mRNA export pathway, the CD83 mRNA is exported by the specific CRM1-mediated pathway, utilized only by a minority of cellular mRNAs. On the protein level, two different isoforms of CD83 exist: a membrane-bound and a soluble form. The isoforms are generated by different subsets of cells, including DCs, T-cells and B-cells, and also differ in their biological function. While the membrane-bound CD83 is of immune stimulatory capacity, activates T-cells and is important for the generation of thymocytes, the soluble CD83 has the opposite effect and has an immune inhibitory capacity. Due to its immune inhibitory function, CD83 has great potential for treatment of autoimmune diseases, for organ transplantations, and for immunotherapy, just to name a few examples. Moreover, some viruses prevent recognition by the host's immune system by specifically targeting CD83 surface expression. PMID- 17334967 TI - Distribution of cren- and euryarchaeota in scots pine mycorrhizospheres and boreal forest humus. AB - Archaeal 16S rRNA gene sequences have been found in a variety of moderate temperature habitats including soil and rhizospheres. In this study, the differences of archaeal communities associated with Scots pine (Pinus sylvestris L.) short roots, different types of mycorrhizospheric compartments, and uncolonized boreal forest humus were tested by direct DNA extraction, polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), and sequencing. The results indicated that mycorrhizal colonization of Scots pine roots substantially influence the archaeal community of pine rhizospheres. Colonization of short roots by most mycorrhizal fungi tested increased both archaeal frequency and diversity. Most of the archaeal sequences encountered in mycorrhizas belonged to the phylum Euryarchaeota, order of Halobacteriales. The difference in archaeal diversity between the mycorrhizospheric compartments and humus was profound. Most compartments with fungal components contained euryarchaeotal 16S rRNA gene sequences, whereas a high diversity of crenarchaeotal sequences and no euryarchaeotal sequences were found in forest humus outside mycorrhizospheres. PMID- 17334965 TI - Effects of spilled oil on bacterial communities of mediterranean coastal anoxic sediments chronically subjected to oil hydrocarbon contamination. AB - The effects of spilled oil on sedimentary bacterial communities were examined in situ at 20 m water depth in a Mediterranean coastal area. Sediment collected at an experimental site chronically subjected to hydrocarbon inputs was reworked into PVC cores with or without a massive addition of crude Arabian light oil ( approximately 20 g kg(-1) dry weight). Cores were reinserted into the sediment and incubated in situ at the sampling site (20 m water depth) for 135 and 503 days. The massive oil contamination induced significant shifts in the structure of the indigenous bacterial communities as shown by ribosomal intergenic spacer analysis (RISA). The vertical heterogeneity of the bacterial communities within the sediment was more pronounced in the oiled sediments particularly after 503 days of incubation. Response to oil of the deeper depth communities (8-10 cm) was slower than that of superficial depth communities (0-1 and 2-4 cm). Analysis of the oil composition by gas chromatography revealed a typical microbial alteration of n-alkanes during the experiment. Predominant RISA bands in oiled sediments were affiliated to hydrocarbonoclastic bacteria sequences. In particular, a 395 bp RISA band, which was the dominant band in all the oiled sediments for both incubation times, was closely related to hydrocarbonoclastic sulfate-reducing bacteria (SRB). These bacteria may have contributed to the main fingerprint changes and to the observed biodegradation of n-alkanes. This study provides useful information on bacterial dynamics in anoxic contaminated infralittoral sediments and highlights the need to assess more precisely the contribution of SRB to bioremediation in oil anoxic contaminated areas. PMID- 17334968 TI - Repellent and adulticide efficacy of a combination containing 10% imidacloprid and 50% permethrin against Aedes aegypti mosquitoes on dogs. AB - This study was conducted to assess the repellent and adulticide efficacy of the combination containing 10% imidacloprid and 50% permethrin against Aedes aegypti mosquitoes on dogs. Blood-feeding success rates of the mosquitoes that were exposed to the treated dogs were 4.9 and 4.4% on days 3 and 7 post the combination application (PCA), respectively, and blood-feeding success rates increased to 6.3, 12.8, and 24.5% on days 14, 21, and 28 PCA, respectively. Blood feeding success rates between the mosquitoes that were exposed to the treated and untreated control dogs on days 3, 7, 14, and 21 PCA were significantly different. All mosquitoes that were exposed to the treated dogs on day 3 PCA died, and mortality rates decreased to 97.1, 77.8, 40.4, and 2.1% on days 7, 14, 21, and 28 PCA, respectively. Mortality rates between the mosquitoes that were exposed to the treated and untreated control dogs on days 3, 7, 14, and 21 PCA were significantly different. This study suggested that this combination can be used to repel and kill mosquitoes on dogs; however, the application of this insecticide combination on dogs needs to be repeated every 3-4 weeks. PMID- 17334969 TI - New record of Afrimenopon waar (Eichler) (Phthiraptera: Menoponidae) from budgerigar Melopsittacus undulatus (Psittaciformes: Psittacidae) from Karachi, Pakistan. AB - Chewing lice of the species Afrimenopon waar (Eichler) were collected from captive budgerigar Melopsittacus undulatus (Shaw) in Pakistan. This is the first record of amblyceran lice from this host. It is also the first record of the genus Afrimenopon from Pakistani region. The primary host species of Afrimenopon waar is the rosy-faced lovebird Agapornis roseicollis (Vieillot). The finding of A. waar on budgerigars is, most likely, a result of a contamination in captivity. Morphological variation and origin of these lice are discussed. PMID- 17334970 TI - [The evaluation of living skills in forensic-psychiatric patients]. AB - The role of daily living skills in forensic psychiatric patients in relation to psychotherapeutic progress and the potential reduction of dangerous behaviour has been neglected in the scientific discussion about clinical instruments for the evaluation of dangerousness and recidivism. This is mainly due to the lack of adequate observationally based instruments allowing for valid and reliable therapeutic assessments. Therefore, a new means of assessment focusing on daily living skills and social risk (the BEST-Index [Behavioural Status Index] was applied to n = 86 German forensic psychiatric patients. Two widely known actuarial instruments tapping violence risk were administered for cross validation (Psychopathy Checklist Revised [PCL-R], HCR-20). Within intervals of nine months, all instruments were applied three times. Sufficient inter rater reliability and good convergent validity of the sub-scales in relation to the actuarial instruments (HCR-20, PCL-R) could be demonstrated; supported by empirical data, clinicians working with the BEST-Index may use it to monitor behavioural change over long treatment periods. It is suggested that treatment planning and evaluation of mentally ill offenders might profit from its use. PMID- 17334972 TI - [Need and utilization of psychosocial care after liver transplantation]. AB - Studies on the need of psychosocial support after liver transplantation (LTX) are rare. At our centre we conducted a survey regarding this question in a one year period with a consecutive sample of 146 patients on average 38 month (SD = 28) after liver transplantation. An assessment of the need was estimated in self assessment, in a rating after completion of an interview, by the estimate of the attending physicians and with the help of standardized questionnaires. 44.5 % of the patients expressed either a present need (15 %) or a need at an earlier time (29.5 %). The physicians classified 20 % as in need of psychosocial care and from the interviewer's point of view 50 % of the patients needed care. The rating correlated to r = 0.32 (physician) and r = 0.55 (interviewer) with the self assessment. In the modified Hornheider questionnaire 18 % of the patients were classified as in need of care. In the German version of the Hospital Anxiety and Depression Scale (HADS-D) 25 % of the patients exhibit increased anxiety values and 16 % of the patients depressive symptoms. The results of the questionnaires are highly intercorrelated and correlated low (estimate of physicians) to medium high (estimate of interviewer) with the ratings of need. Grouped according to their self-assessment of need, the groups of patients differ significantly in the applied questionnaires. Patients who do not indicate any need show the lowest anxiety and depression values and report the fewest problems. The offer of psychosocial support in the survey period was utilized by 27 of the participating patients (19 %). Altogether we can estimate the current need at a certain time between 15 and 20 % and a total need after LTX up to 50 %. These results require further examination and the appropriate form of psychosocial offers for these patients should be developed in further research. PMID- 17334971 TI - [Perceived stigmatisation following laryngectomy]. AB - Patients who have had a cancer-related total laryngectomy (N = 217) were studied in order to investigate possible associations between perceived stigmatisation and such physical and social factors as: type and intelligibility of the replacement alaryngeal voice, mental health, and gender. The laryngectomees participated in structured interviews. The German questionnaire "Fragebogen zur pyschosozialen Anpassung nach Laryngectomie" (Questionnaire for Psychosocial Adjustment after Laryngectomy, FPAL) was used to measure patients' perceived stigmatisation. Speech intelligibility was measured both by using the Post laryngectomy Telephone Intelligibility Test (PLTT) and by taking into account patients' own evaluation of how well they are able to speak. Patients' mental health was measured with the Hospital Anxiety and Depression Scale (HADS). Multi factorial analysis of variance and covariance was used to test the effects of the parameters. Results show that stigmatisation is associated with anxiety (F = 5.992, p < 0.05 and F = 12.895, p < 0.001) but not with speech intelligibility, alaryngeal voice type, gender, or depression. There is a correspondence between the degree to which patients feel stigmatised because of their voice or tracheostomy and their sense of loneliness (F = 4.917, p < 0.05 and F = 6.271, p < 0.05). We can conclude that perceived stigmatisation is frequently accompanied by anxiety and loneliness. Men are apparently as often concerned as women. Stigmatisation is not increased when patients do use electronic devices for communication, and it is not lower in patients whose operation dates back several years. PMID- 17334973 TI - [Utilization of self-help groups and psychotherapy after psychosomatic psychotherapeutic in-patient treatment]. AB - Until now little is known about the role of participation in self-help groups alone or combined with psychotherapy in post-in-patient care. In the present study 2933 patients were questioned about their experience of self-help groups and psychotherapy after discharge from a clinic for psychosomatic medicine and psychotherapy. Nearly 8 % of them utilized self-help groups (mostly combined with out-patient psychotherapy), and altogether 68 % out-patient psychotherapy following in-patient treatment. Patients without out-patient treatment were psychologically less burdened and had better resources than participants of self help groups or psychotherapy. Self-help group members differed from patients in out-patient psychotherapy by expressing a more positive opinion of groupwork and higher openness to new experiences. Additionly, they had discussed the topic of self-help groups more frequently with their therapists. This may be a starting point for promoting more self-help activities of patients in the future. PMID- 17334974 TI - [Predictors of migraine attacks]. AB - Little is known about psychological and social factors influencing the frequency of migraine attacks. The aim of the present study was to study whether anger, anger-expression, anxiety, depression, somatization and childhood adversities influence the frequency of migraine attacks. 53 female patients suffering from migraine with a mean monthly headache frequency of 6.85 took part. Groups of patients with 6 or less monthly attacks (N = 27) vs. patients with 7 or more days (N = 26) were formed. Logistic regression analysis revealed, that only the variable "anger-in" resulted in an improvement of prediction of group-membership (rate of correct classified cases: 69.8 %). Tendency to repress anger increases the probability to be a member of the group with frequent attacks. This result points out the relevance of anger-expression and -perception for the psychotherapy of migraine. PMID- 17334975 TI - Animal models for implant biomaterial research in bone: a review. AB - Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species showed the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrated a good likeness with human bone however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling between the species is likely to assist in the selection of a suitable species for a defined research question. PMID- 17334976 TI - In-vitro interactions of human chondrocytes and mesenchymal stem cells, and of mouse macrophages with phospholipid-covered metallic implant materials. AB - Phospholipid-coatings on metallic implant surfaces were evaluated in terms of adhesion, proliferation and matrix production of skeletal cells, and of macrophage stimulation. The working hypothesis is that mimicking a model biomembrane by phospholipids on surfaces to which cells adhere, the surface recognition by surrounding cells is altered. In this study, 1) mirror-like polished Ti-6Al-7Nb and 2) porous Ti-6Al-4V specimens were covered with the phospholipids POPE (palmitoyl-oleoyl phosphatidyl-ethanolamine) and POPC (palmitoyl-oleoyl phosphatidyl-choline), and the interactions of a) human articular chondrocytes (HAC), b) human mesenchymal stem cells (HMSC), and c) mouse macrophages (RAW 264.7Rpar; were tested in vitro. On POPE-covered polished surfaces adherence of HAC (42% of seeded cells after 2 hrs) and metabolic activity (MTT after 3 days) were reduced, while on porous surfaces 99% HAC adhered, and metabolic activity was significantly increased, compared to respective native surfaces. On both POPE-covered surfaces the chondrocyte phenotype was present. After 3 weeks of chondrogenic differentiation, cartilage matrix production (measuring chondroitin sulphate per HAC number) was significantly increased by about 30% on both POPE-covered metallic surfaces. On both POPC-covered surfaces nearly no adhering and surviving HAC were found. HMSC grown on POPE-covered porous substrates showed osteogenic differentiation by improved osteopontin and collagen I expression in RT-PCR, and osteocalcin fluorescence and bone nodule formation was only detectable on POPE-covered porous surfaces. In contrast to POPC and other phospholipids used as positive controls, POPE did not stimulate the NO production in mouse macrophage cultures. We therefore conclude that a phospholipid coating by POPE shows potential as surface modification for metallic implant materials. PMID- 17334977 TI - Health insurance coverage and the use of preventive services by Mexican adults. AB - The lack of health insurance coverage could be a potentially important deterrent to the use of preventive health care by older adults with high rates of chronic co-morbidities. We use survey data from 12 100 Mexican adults ages 50 and older who participated in the 2001 Mexican Health and Aging Study (MHAS) to analyze the relation between health insurance coverage and the use of preventive health-care services in Mexico. Uninsured adults were less likely to use preventive screenings for hypertension, high cholesterol, diabetes and (breast, cervical and prostate) cancer than insured adults. After adjusting for other factors affecting preventive care utilization in a logistic regression model, we found that these results still hold for high cholesterol and diabetes screening. Similar results hold for the population not working during the survey week and for adults earning below 200% of the poverty line. Our results suggest that insured adults are in a relatively better position to detect some chronic diseases - and have them treated promptly - than uninsured adults because they have better access to cost effective preventive screenings. Recent public policy initiatives to increase health insurance coverage rates in Mexico could lead to substantially higher preventive health-care utilization rates and improvements in population health. PMID- 17334979 TI - Methylation patterns of IGFBP7 in colon cancer cell lines are associated with levels of gene expression. AB - Altered expression of insulin-like growth factor binding protein 7 (IGFBP7) has been found in colon cancer, but the exact regulatory mechanism has not been fully investigated. In order to elucidate the mechanisms underlying aberrant IGFBP7 expression in colon cancer, we used bisulphite sequencing PCR (BSP) to detect the detailed methylation profiles of the IGFBP7 5' CpG island. Exon 1 of the IGFBP7 gene was highly methylated in IGFBP7-negative cell lines but unmethylated in IGFBP7-positive lines. The methylation status of the promoter region and the intron 1 region was not so discriminating in IGFBP7-positive and -negative cell lines. Methylation-specific PCR (MSP) confirmed the hypermethylation of IGFBP7 exon 1 in IGFBP7-negative cell lines. Treatment with 5-aza-2'-deoxycytidine (5 aza-dC) induced demethylation of the CpG island in exon 1 of IGFBP7, as examined by both MSP and bisulphate genomic sequencing. Furthermore, the expression of IGFBP7 was restored, as detected by both RT-PCR and immunocytochemistry. Our study is the first to provide detailed methylation profiles of the IGFBP7 5' CpG island and shows that hypermethylation of the CpG island in exon 1 of IGFBP7 is closely related to the absence of its expression in colon cancer cells. PMID- 17334978 TI - Glutamate measurement in Parkinson's disease using MRS at 3 T field strength. AB - Loss of nigral dopamine neurons in Parkinson's disease induces abnormal activation of glutamate systems in the basal ganglia. The purpose of this study was to assess these changes in the lentiform nucleus using MRS with optimized glutamate sensitivity (TE-averaged method). Ten patients with Parkinson's disease and 10 healthy controls were examined. Compared with healthy controls, no significant differences in glutamate were measured in patients, but a trend to lower total creatine was observed. PMID- 17334980 TI - Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS-1). AB - Thymomas are thymic epithelial neoplasms, associated with a variety of autoimmune disorders (especially myasthenia gravis), that apparently result from aberrant intra-tumourous thymopoiesis and export of inefficiently tolerized T-cells to the periphery. The autoimmune regulator (AIRE) drives the expression of self-antigens in the thymic medulla and plays an essential role in 'central' tolerance in both humans and mice. However, while inactivating AIRE mutations result in the 'autoimmune polyendocrinopathy syndrome type 1' (APS-1), its major features are not well reproduced in AIRE-knock-out mice. Therefore, alternative human disease scenarios with concomitant AIRE deficiency may be valuable tools to test conclusions drawn from mouse models. Here we show, in a large series, that approximately 95% of thymoma patients are 'chimeric'; expression of AIRE and major AIRE-related autoantigens (eg insulin) were undetectable in their tumours but maintained in their remnant thymic tissue and lymph nodes. Notably, despite the AIRE-deficient thymopoiesis in thymomas, disorders and autoantibodies typical of APS-1 were distinctly uncommon in these patients. The one striking similarity was in the recently observed neutralizing anti-type I interferon (IFN) antibodies, which are found at diagnosis in 100% of patients with APS-1 and in approximately 60% of patients with thymomas, as we show here. We conclude that APS-1 type autoantigens must be protected from autoimmunity by mechanisms that do not extend to the muscle autoantigens so frequently targeted in thymoma patients but so rarely recognized in APS-1. Thus our findings argue strongly for a tolerogenic function of AIRE beyond its role in negative T-cell selection in human thymopoiesis, and/or for specific autoimmunization against muscle in thymomas. PMID- 17334982 TI - Packaging of prions into exosomes is associated with a novel pathway of PrP processing. AB - Prion diseases are fatal, transmissible neurodegenerative disorders associated with conversion of the host-encoded prion protein (PrP(C)) into an abnormal pathogenic isoform (PrP(Sc)). Following exposure to the infectious agent (PrP(Sc)) in acquired disease, infection is propagated in lymphoid tissues prior to neuroinvasion and spread within the central nervous system. The mechanism of prion dissemination is perplexing due to the lack of plausible PrP(Sc)-containing mobile cells that could account for prion spread between infected and uninfected tissues. Evidence exists to demonstrate that the culture media of prion-infected neuronal cells contain PrP(Sc) and infectivity but the nature of the infectivity remains unknown. In this study we have identified PrP(C) and PrP(Sc) in association with endogenously expressing PrP neuronal cell-derived exosomes. The exosomes from our prion-infected neuronal cell line were efficient initiators of prion propagation in uninfected recipient cells and to non-neuronal cells. Moreover, our neuronal cell line was susceptible to infection by non-neuronal cell-derived exosome PrP(Sc). Importantly, these exosomes produced prion disease when inoculated into mice. Exosome-associated PrP is packaged via a novel processing pathway that involves the N-terminal modification of PrP and selection of distinct PrP glycoforms for incorporation into these vesicles. These data extend our understanding of the relationship between PrP and exosomes by showing that exosomes can establish infection in both neighbouring and distant cell types and highlight the potential contribution of differentially processed forms of PrP in disease distribution. These data suggest that exosomes represent a potent pool of prion infectivity and provide a mechanism for studying prion spread and PrP processing in cells endogenously expressing PrP. PMID- 17334981 TI - Dynamic intracellular survivin in oral squamous cell carcinoma: underlying molecular mechanism and potential as an early prognostic marker. AB - Survivin functions as an apoptosis inhibitor and a regulator of cell division in many tumours. The intracellular localization of survivin in tumours has been suggested as a prognostic marker. However, current reports are inconsistent and the underlying molecular mechanisms are not understood. The present study has examined the localization and prognostic value of nuclear and cytoplasmic survivin in the pre-therapeutic biopsies from 71 oral and oropharyngeal squamous carcinoma (OSCC) patients. Statistical analysis indicated that preferential nuclear versus cytoplasmic survivin correlated with favourable versus unfavourable disease outcome. Uni- and multi-variate analysis showed that in contrast to total survivin expression, the difference between nuclear and cytoplasmic survivin was a strong predictor for relapse-free survival (p=0.0003). As a potential underlying molecular mechanism, it is shown in OSCC cell lines that predominantly cytoplasmic survivin mediates protection against chemo- and radio-therapy-induced apoptosis. Importantly, the cytoplasmic localization of survivin is regulated by its nuclear export signal (NES), and export-deficient nuclear survivin is not cytoprotective. This study suggests that the difference between cytoplasmic and nuclear survivin is an indicator for survivin activity in tumour cells. Thus, this difference may serve as a predictive marker of outcome in OSCC patients undergoing multi-modality therapy. The pharmacogenetic interference with survivin's cytoplasmic localization is also to be pursued as a potential therapeutic strategy. PMID- 17334984 TI - Vibrational anharmonic calculations in solution: performance of various DFT approaches. AB - We report anharmonic spectra calculated for formaldehyde in acetonitrile solution using the quartic force field obtained for various DFT/solvent coupled models. A statistical study has been carried out for each mode by using several classes of DFT functionals and comparing them to the reference ab-initio CCSD(T)/cc-pVQZ calculations. Results lead to the recommended use of hybrid functionals associated with the 6-31+G** basis set and the Polarized Continuum model (PCM) to predict the expected shifts relative to the gas phase. PMID- 17334985 TI - A DFT study on the dimerization of C62, H2-C62, and F2-C62. AB - On the basis of calculations using the density functional theory, we show that C(62), a recently synthesized nonclassical fullerene, will presumably undergo dimerization with various isomers at elevated temperatures. This is shown by calculating the dimerization energy and the activation barrier of the dimerization. Eight possible isomers of the dimer were identified, all of which are more stable than the two isolated monomers. The relative stability of various isomers depends upon the kind of C=C bonds within the four-membered carbon ring involved in the dimerization. In addition, similar calculations were performed for the monomers and dimers of H(2)-C(62) and F(2)-C(62). Six isomers were identified for each of the dimers. Although less pronounced than the case of the C(62) dimer, all isomers of the H(2)-C(62) dimer are appreciably more stable than the individual monomers. Although a large steric repulsion due to F atoms significantly reduces the stability of F(2)-C(62) dimer, its two isomers are still more stable than separate monomers. PMID- 17334983 TI - Upfront window trial of topotecan in previously untreated children and adolescents with poor prognosis metastatic osteosarcoma: children's Cancer Group (CCG) 7943. AB - BACKGROUND: Patients with metastatic osteosarcoma have a poor prognosis. The objectives of the study were to determine the antitumor activity and toxicity of topotecan (daily x5) in newly diagnosed patients with metastatic osteosarcoma followed by chemotherapy (ifosfamide, carboplatin, etoposide [ICE], alternating with cisplatin and doxorubicin [CD]). METHODS: Newly diagnosed patients (< or =30 years of age) with extensive metastatic disease (primary and > or =5 pulmonary nodules and/or bone metastases) with normal hepatic, renal, and cardiac function were eligible. Patients were eligible to receive further topotecan after standard chemotherapy if they exhibited a response. Twenty-eight patients were enrolled. Seventeen had metastases to the lung only and 11 had metastases to the bone or multiple sites. Of 28 patients enrolled, 27 could be evaluated for response. A limited dose escalation was incorporated. RESULTS: No responses were seen in the 11 patients treated at 3 mg/m(2)/day. One partial response (PR) and 1 clinical response (CLR) were reported among 15 patients who received topotecan at 3.5 mg/m(2)/day. No dose-limiting toxicity was observed. Principal nondose-limiting toxicities were hematologic and gastrointestinal. The 2- and 5-year event-free survival rates were low, 7% and 4%, respectively, but the 2- and 5-year overall survival rates were 44% and 22%, respectively. CONCLUSIONS: Topotecan at dose of 3.5 mg/m(2)/day can be safely administered upfront to newly diagnosed patients without excessive toxicity. Insufficient activity was seen with topotecan in this schedule to warrant further studies in osteosarcoma. The combination of ICE and CD was tolerable when delivered after initial topotecan therapy. PMID- 17334986 TI - Linear regression model of DNA sequences and its application. AB - We constructed six new models to analyze the DNA sequences. First, we regarded a DNA primary sequence as a random process in t and gave three ways to define nucleotides' random distribution functions. We extracted some parameters from the linear model and analyzed the changes of the nucleotides' distributions. In order to facilitate the comparison of DNA sequences, we proposed two ways to measure their similarities. Finally, we compared the six models by analyzing the similarities of the DNA primary sequences presented in Table 1 and selected the optimal one. PMID- 17334988 TI - Cytopathological diagnosis in a cancer registry: a useful diagnostic tool? AB - BACKGROUND: To assess the role of cytology in tumor diagnosis and to explore the potential of this technique to improve tumor registry quality, the authors investigated the role of cytology as a diagnostic tool in registry databases. METHODS: Through the Italian Network of Cancer Registry (AIRTum) archive, the authors retrieved tumors diagnosed during the years 1983-2002 from several registries, Varese, Torino, Ragusa, Ferrara, Genova, and the Tuscan Cancer Registry. The authors then analyzed the amount of morphological confirmation by topographic code, distinguishing cytological from histological diagnosis. The authors analyzed, only for the Tuscan Cancer Registry, the amount of morphological confirmation by both histological and cytological diagnosis and demonstrated the variation of cytological confirmation with stage of tumor. RESULTS: The better morphological modality for diagnosis was rarely cytology, particularly among lung and pleural tumors; when considered together with histological analysis, cytology examination was often reported in cervical uterine and breast tumors. The usefulness of cytology increases with tumor stage, particularly in sites where biopsy is performed with difficulty. CONCLUSIONS: Cytology may be useful to improve tumoral characterization in advanced stages or in sites inaccessible for histology; moreover, cytology is useful as an initial detector of pathology, prior to histology. A prospect of improvement in diagnostic cytopathology and the use of ancillary techniques, such as molecular biology, could help clinicians and could increase the accuracy of cancer registration. PMID- 17334987 TI - Interfacing Q-Chem and CHARMM to perform QM/MM reaction path calculations. AB - A hybrid quantum mechanical/molecular mechanical (QM/MM) potential energy function with Hartree-Fock, density functional theory (DFT), and post-HF (RIMP2, MP2, CCSD) capability has been implemented in the CHARMM and Q-Chem software packages. In addition, we have modified CHARMM and Q-Chem to take advantage of the newly introduced replica path and the nudged elastic band methods, which are powerful techniques for studying reaction pathways in a highly parallel (i.e., parallel/parallel) fashion, with each pathway point being distributed to a different node of a large cluster. To test our implementation, a series of systems were studied and comparisons were made to both full QM calculations and previous QM/MM studies and experiments. For instance, the differences between HF, DFT, MP2, and CCSD QM/MM calculations of H2O...H2O, H2O...Na+, and H2O...Cl- complexes have been explored. Furthermore, the recently implemented polarizable Drude water model was used to make comparisons to the popular TIP3P and TIP4P water models for doing QM/MM calculations. We have also computed the energetic profile of the chorismate mutase catalyzed Claisen rearrangement at various QM/MM levels of theory and have compared the results with previous studies. Our best estimate for the activation energy is 8.20 kcal/mol and for the reaction energy is -23.1 kcal/mol, both calculated at the MP2/6-31+G(d)//MP2/6-31+G(d)/C22 level of theory. PMID- 17334989 TI - Maternal and embryonic sources of tyrosine hydroxylase during Drosophila embryogenesis. AB - Tyrosine hydroxylase (TH), the enzyme which catalyzes the conversion of tyrosine to L-DOPA and is rate limiting in catecholamine biosynthesis, is biochemically expressed in late stage wild-type Drosophila oocytes as well as in early embryogenesis. Null mutant alleles of TH (pale) are embryonic lethals with death occurring in the late embryonic or early larval periods of development. Staging of embryos demonstrated that inhibition of the enzymatic activity of TH by alpha methyl-p-tyrosine (alphaMT) retards the progression of embryos primarily during the organogenesis stages of embryonic development, with lesser effects on earlier and later stages. On the other hand, time of gene action studies with a conditional temperature sensitive pale mutant (ple(ts1)) at its restrictive temperature (29 degrees C) indicate an onset of tyrosine hydroxylase gene action beginning in the oocyte stage of development. Thus, maternal as well as embryonic effects on the secretion and/or functionality of this enzyme may play roles in the early developmental program of the organism. PMID- 17334990 TI - Evaluation of p16INK4a expression in ThinPrep cervical specimens with the CINtec p16INK4a assay: correlation with biopsy follow-up results. AB - BACKGROUND: The aim of this study was to examine p16(INK4a) protein expression in ThinPrep (Cytyc Corporation, Marlborough, Mass) cervical specimens by using the CINtec p16(INK4a) Cytology Kit (Dako, Glostrup, Denmark). The ability of this assay to accurately identify underlying high-grade lesions was assessed by using follow-up biopsies and comparing these results with Hybrid Capture 2 (Digene, Gaithersburg, Md) high-risk HPV (hc(2)) results. METHODS: Three hundred ninety eight residual ThinPrep samples were collected, and histological follow-up data were retrieved for abnormal cytology specimens. After preparation of a Papanicolaou-stained slide, a second slide was processed in preparation for p16(INK4a) immunostaining. High-risk human papillomavirus testing (hc(2)) was also performed. RESULTS: Of the 163 cytologically abnormal samples, 6-month biopsy follow-up data were available for 45% of the specimens. At initial blinded evaluation, 21 of the 26 cases with cervical intraepithelial neoplasia (CIN) II/III follow-up were positive for p16(INK4a), yielding an overall diagnostic sensitivity of 81%; 29 of the 47 cases diagnosed as CIN I or less were p16(INK4a) negative, yielding a diagnostic specificity of 62%. In comparison, the hc(2) test results indicated a diagnostic sensitivity of 100% with a diagnostic specificity of 15%. After review of selected cases with CIN II/III follow-up, 25 of 26 slides were deemed to be positive for p16(INK4a), increasing the diagnostic sensitivity to 96%. CONCLUSIONS: The CINtec p16(INK4a) Cytology Kit, in combination with ThinPrep cervical samples, allowed clear evaluation of p16(INK4a) protein overexpression. Diagnostic specificity of the CINtec p16(INK4a) assay was significantly improved relative to hc(2). To increase p16(INK4a) immunostaining in abnormal cells, a modified kit version with improved staining performance has been developed and is currently being evaluated. PMID- 17334991 TI - Parathyroid proliferations: a source of diagnostic pitfalls in FNA of thyroid. AB - BACKGROUND: With wide use of fine-needle aspirates (FNA) for investigation of thyroid nodules, a growing number of parathyroid glands are being inadvertently aspirated for cytologic study. Aiming to determine the effectiveness of FNA to differentiate between parathyroid and thyroid lesions, all cases aspirated initially as thyroid nodules and that had a final histologic diagnosis of parathyroid lesion were retrieved from the authors' files and were systematically reviewed to delineate possible specific diagnostic criteria. METHODS: From a total of 90,000 FNA diagnoses of thyroid nodules, 4740 cases were isolated for which a final histologic diagnosis was available. Among these, 29 cases with a final histologic diagnosis of a parathyroid lesion were identified and reanalyzed according to the initial cytologic diagnoses. Furthermore, the FNA smears were reviewed, and specific features were recorded. RESULTS: FNA failed to recognize the parathyroid origin of the lesions in all but 2 cases with known hyperparathyroidism. Most aspirates were misinterpreted either as suspicious for or as thyroid neoplasms because of high cellularity and absence of colloid. Histologically, the lesions proved to be parathyroid hyperplasia, adenoma, or carcinoma. Specific cytologic features are discussed. CONCLUSION: A safe differential diagnosis between thyroid and parathyroid disease on morphological ground in cytologic smears is difficult due to overlapping features of these lesions. To avoid surgical mismanagement, it is essential, in every highly cellular lesion seen in the context of a colloid-free background, to consider and report the possibility of a parathyroid lesion, thus enabling the clinician to proceed to a more detailed preoperative evaluation in this direction. PMID- 17334992 TI - Duplication of 17(p11.2p11.2) in a male child with autism and severe language delay. AB - Duplications of 17(p11.2p11.2) have been associated with various behavioral manifestations including attention deficits, obsessive-compulsive symptoms, autistic traits, and language delay. We are conducting a genetic study of autism and are screening all cases for submicroscopic chromosomal abnormalities, in addition to standard karyotyping, and fragile X testing. Using array-based comparative genomic hybridization analysis of data from the Affymetrix GeneChip(R) Human Mapping Array set, we detected a duplication of approximately 3.3 Mb on chromosome 17p11.2 in a male child with autism and severe expressive language delay. The duplication was confirmed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction. Gene expression analyses revealed increased expression of three candidate genes for the Smith Magenis neurobehavioral phenotype, RAI1, DRG2, and RASD1, in transformed lymphocytes from Case 81A, suggesting gene dosage effects. Our results add to a growing body of evidence suggesting that duplications of 17(p11.2p11.2) result in language delay as well as autism and related phenotypes. As Smith-Magenis syndrome is also associated with language delay, a gene involved in acquisition of language may lie within this interval. Whether a parent of origin effect, gender of the case, the presence of allelic variation, or changes in expression of genes outside the breakpoints influence the resultant phenotype remains to be determined. PMID- 17334993 TI - A novel missense mutation in the NDP gene in a child with Norrie disease and severe neurological involvement including infantile spasms. AB - Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness and in some cases, mental retardation and deafness. Other neurological complications, particularly epilepsy, are rare. We report on a novel mutation identified in a patient with ND and profound mental retardation. The patient was diagnosed at the age of 6 months due to congenital blindness. At the age of 8 months he developed infantile spasms, which were diagnosed at 11 months as his EEG demonstrated hypsarrhythmia. Mutation analysis of the ND gene (NDP) of the affected child and his mother revealed a novel missense mutation at position c.134T > A resulting in amino acid change at codon V45E. To the best of our knowledge, such severe neurological involvement has not been previously reported in ND patients. The severity of the phenotype may suggest the functional importance of this site of the NDP gene. PMID- 17334994 TI - Invited comment: gastroschisis. PMID- 17334995 TI - An Alu retrotransposition-mediated deletion of CHD7 in a patient with CHARGE syndrome. AB - CHD7 mutations account for about 60-65% among more than 200 CHARGE syndrome cases. When rare whole gene deletion cases associated with chromosomal abnormalities are excluded, all mutations of CHD7 reported to date have been point mutations and small deletions and insertions, rather than exonic deletions. To test whether exonic deletions represent a common pathogenic mechanism, we assessed exon copy number by using a recently developed method, the multiplex PCR/liquid chromatography assay (MP/LC). Multiple exons were amplified using unlabeled primers, then separated by ion-pair reversed-phase high-performance liquid chromatography, and quantitated by fluorescence detection using a post column intercalation dye under the premise that the relative peak intensities for each target directly reflect exon copy number. By using MP/LC, we identified one CHARGE syndrome patient who had a de novo deletion encompassing exons 8-12 among 13 classic CHARGE patients in whom screening by denaturing high-performance liquid chromatography (DHPLC) failed to identify point mutations and small insertions/deletions in CHD7. This is the first CHARGE patient who was documented to have exonic deletion of CHD7. The deletion closely recapitulated the Alu mediated inactivation of the human CMP-N-acetylneuraminic acid hydroxylase gene (CMP-Neu5Ac hydroxylase), which is regarded as a novel molecular mechanism in the evolution from non-human primates to humans. As demonstrated in this study, MP/LC is a promising method for characterizing exonic deletions, which are largely left unexamined in most routine mutation analysis. PMID- 17334996 TI - High-resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization. AB - A BAC-array platform for comparative genomic hybridization was constructed from a library of 32,433 clones providing complete genome coverage, and evaluated by screening for DNA copy number changes in 10 breast cancer cell lines (BT474, MCF7, HCC1937, SK-BR-3, L56Br-C1, ZR-75-1, JIMT1, MDA-MB-231, MDA-MB-361, and HCC2218) and one cell line derived from fibrocystic disease of the breast (MCF10A). These were also characterized by gene expression analysis and found to represent all five recently described breast cancer subtypes using the "intrinsic gene set" and centroid correlation. Three cell lines, HCC1937 and L56BrC1 derived from BRCA1 mutation carriers and MDA-MB-231, were of basal-like subtype and characterized by a high frequency of low-level gains and losses of typical pattern, including limited deletions on 5q. Four estrogen receptor positive cell lines were of luminal A subtype and characterized by a different pattern of aberrations and high-level amplifications, including ERBB2 and other 17q amplicons in BT474 and MDA-MB-361. SK-BR-3 cells, characterized by a complex genome including ERBB2 amplification, massive high-level amplifications on 8q and a homozygous deletion of CDH1 at 16q22, had an expression signature closest to luminal B subtype. The effects of gene amplifications were verified by gene expression analysis to distinguish targeted genes from silent amplicon passengers. JIMT1, derived from an ERBB2 amplified trastuzumab resistant tumor, was of the ERBB2 subtype. Homozygous deletions included other known targets such as PTEN (HCC1937) and CDKN2A (MDA-MB-231, MCF10A), but also new candidate suppressor genes such as FUSSEL18 (HCC1937) and WDR11 (L56Br-C1) as well as regions without known genes. The tiling BAC-arrays constitute a powerful tool for high-resolution genomic profiling suitable for cancer research and clinical diagnostics. PMID- 17334997 TI - Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas. AB - Fusion of the CREB regulated transcription coactivator CRTC1 (a.k.a. MECT1, TORC1, or WAMTP1) to the Notch coactivator MAML2 is a characteristic feature of low-grade mucoepidermoid carcinomas of salivary and bronchial glands. The CRTC1 MAML2 fusion protein acts by inducing transcription of cAMP/CREB target genes, and this activity is crucial for the transforming properties of the protein. Here we show that the CRTC1-MAML2 gene fusion is also frequent in benign hidradenomas of the skin. FISH and RT-PCR analyses revealed that hidradenomas are genetically heterogeneous, and that 10 of the 20 tumors analyzed (50%) contained the CRTC1 MAML2 gene fusion and expressed the resulting fusion transcript. Immunohistochemical analysis demonstrated expression of the fusion protein in the majority of tumor cells, including clear cells, poroid cells, and cells with epidermoid and ductal differentiation. In addition, we could show that all fusion positive tumors were morphologically distinguished by the presence of more or less abundant areas of clear cells whereas all fusion-negative tumors lacked clear cells. Our findings thus demonstrate that the CRTC1-MAML2 gene fusion is frequent in hidradenomas and is associated with clear cell variants of this tumor. Taken together, the present and previous observations indicate that the CRTC1-MAML2 fusion is etiologically linked to benign and low-grade malignant tumors originating from diverse exocrine glands rather than being linked to a separate tumor entity. PMID- 17334998 TI - Pan-myocardial expression of Cre recombinase throughout mouse development. AB - Mouse-lines expressing Cre recombinase in a tissue-specific manner are a powerful tool in developmental biology. Here, we report that a 3 kb fragment of the Xenopus laevis myosin light-chain 2 (XMLC2) promoter drives Cre recombinase expression in a cardiac-restricted fashion in the mouse embryo. We have isolated two XMLC2-Cre lines that express recombinase exclusively within cardiomyocytes, from the onset of their differentiation in the cardiac crescent of the early embryo. Expression is maintained throughout the myocardium of the embryonic heart tube and subsequently the mature myocardium of the chambered heart. Recombinase activity is detected in all myocardial tissue, including the pulmonary veins. One XMLC2-Cre line shows uniform expression while the other only expresses recombinase in a mosaic fashion encompassing less than 50% of the myocardial cells. Both lines cause severe cardiac malformations when crossed to a conditional Tbx5 line, resulting in embryonic death at midgestation. Optical projection tomography reveals that the spectrum of developmental abnormalities includes a shortening of the outflow tract and its abnormal alignment, along with a dramatic reduction in trabeculation of the ventricular segment of the looping heart tube. PMID- 17335000 TI - Invariance of the zinc finger module: a comparison of the free structure with those in nucleic-acid complexes. PMID- 17335001 TI - Retinopathy mutations in the bZIP protein NRL alter phosphorylation and transcriptional activity. AB - The transcription factor neural retina leucine zipper (NRL) is required for rod photoreceptor differentiation during mammalian retinal development. NRL interacts with CRX, NR2E3, and other transcription factors and synergistically regulates the activity of photoreceptor-specific genes. Mutations in the human NRL gene are associated with retinal degenerative diseases. Here we report functional analyses of 17 amino acid variations and/or mutations of NRL. We show that 13 of these lead to changes in NRL phosphorylation. Six mutations at residues p.S50 (c.148T>A, c.148T>C, and c.149C>T) and p.P51 (c.151C>A, c.151C>T, and c.152C>T), identified in patients with autosomal dominant retinitis pigmentosa, result in a major NRL isoform that exhibits reduced phosphorylation but enhanced activation of the rhodopsin promoter. The truncated NRL mutant proteins-p.L75fs (c.224_225insC) and p.L160fs (c.459_477dup)-do not localize to the nucleus because of the absence of bZIP domain. The p.L160P (c.479T>C), p.L160fs, and p.R218fs (c.654delC) mutant proteins do not bind to the NRL-response element, as revealed by electrophoretic mobility shift assays. These three and p.S225N (c.674G>A) mutant show reduced transcriptional activity and may contribute to recessive disease. The p.P67S (c.199C>T) and p.L235F (c.703C>T) variations in NRL do not appear to directly cause retinitis pigmentosa, while p.E63K (c.187G>A), p.A76V (c.227C>T), p.G122E (c.365G>A), and p.H125Q (c.375C>G) are of uncertain significance. Our results support the notion that gain-of-function mutations in the NRL gene cause autosomal dominant retinitis pigmentosa while loss-of-function NRL mutations lead to autosomal recessive retinitis pigmentosa. We propose that differential phosphorylation of NRL fine-tunes its transcriptional regulatory activity, leading to a more precise control of gene expression. PMID- 17335002 TI - Examination of the decline in symptoms of anxiety and depression in generalized anxiety disorder: impact of anxiety sensitivity on response to pharmacotherapy. AB - Pharmacotherapy is an effective treatment for generalized anxiety disorder (GAD), but few studies have examined the nature of decline of anxiety and depression during pharmacotherapy for GAD and even fewer studies have examined predictors of symptom decline. This study examined the decline in symptoms of anxiety and depression in patients with GAD during a 6-week open trial of fluoxetine. Growth curve analyses indicated that pharmacotherapy with fluoxetine led to significant declines in symptoms of anxiety and depression over the 6 weeks of treatment. However, the decay slope observed for anxiety symptoms was significantly greater than that for depressive symptoms. Further analyses revealed that the decline in anxiety remained significant after accounting for the changes in symptoms of depression. However, the effect of treatment on depression was no longer significant after controlling for the reduction in anxiety symptoms. Overall anxiety sensitivity (AS) did not moderate the level of reduction in symptoms of anxiety or depression during pharmacotherapy. However, AS specific to physical concerns demonstated a marginal negative association with decline in anxiety and depression. AS specific to social concerns also demonstrated a marginal negative association with decline in anxiety symptoms. These findings suggest that the decline in anxiety symptoms is independent of the decline in symptoms of depression during pharmacotherapy for GAD and specific AS dimensions may predict symptom change in GAD. PMID- 17335003 TI - Effects of amino acid composition, finite size of proteins, and sparse statistics on distance-dependent statistical pair potentials. AB - Statistical distance dependent pair potentials are frequently used in a variety of folding, threading, and modeling studies of proteins. The applicability of these types of potentials is tightly connected to the reliability of statistical observations. We explored the possible origin and extent of false positive signals in statistical potentials by analyzing their distance dependence in a variety of randomized protein-like models. While on average potentials derived from such models are expected to equal zero at any distance, we demonstrate that systematic and significant distortions exist. These distortions originate from the limited statistical counts in local environments of proteins and from the limited size of protein structures at large distances. We suggest that these systematic errors in statistical potentials are connected to the dependence of amino acid composition on protein size and to variation in protein sizes. Additionally, atom-based potentials are dominated by a false positive signal that is due to correlation among distances measured from atoms of one residue to atoms of another residue. The significance of residue-based pairwise potentials at various spatial pair separations was assessed in this study and it was found that as few as approximately 50% of potential values were statistically significant at distances below 4 A, and only at most approximately 80% of them were significant at larger pair separations. A new definition for reference state, free of the observed systematic errors, is suggested. It has been demonstrated to generate statistical potentials that compare favorably to other publicly available ones. PMID- 17335005 TI - Activation loop phosphorylation-independent kinase activity of human protein kinase C zeta. AB - Atypical protein kinase C zeta (PKCzeta) plays an important role in cell proliferation and survival. PKCzeta and its truncated form containing only the kinase domain, CATzeta, have been reported to be activated by the phosphorylation of threonine 410 in the activation loop. We expressed both the full length PKCzeta and CATzeta in a baculovirus/insect cell over-expression system and purified the proteins for biochemical characterization. Ion exchange chromatography of CATzeta revealed three species with different levels of phosphorylation at Thr-410 and allowed the isolation of the CATzeta protein devoid of phosphorylation at Thr-410. All three species of CATzeta were active and their activity was not correlated with phosphorylation at Thr-410, indicating that the kinase activity of CATzeta did not depend solely on activation loop phosphorylation. Tyrosine phosphorylation was detected in all three species of CATzeta and the full length PKCzeta. Homology structural modeling of PKCzeta revealed a conserved, predicted-to-be phosphorylated tyrosine residue, Tyr-428, in the close proximity of the RD motif of the catalytic loop and of Thr-410 in the activation loop. The structural analysis indicated that phospho-Tyr-428 would interact with two key, positively-charged residues to form a triad conformation similar to that formed by phospho-Thr-410. Based on these observations, it is possible that the Thr-410 phosphorylation-independent kinase activity of CATzeta is regulated by the phosphorylation of Tyr-428. This alternative mode of PKCzeta activation is supported by the observed stimulation of PKCzeta kinase activity upon phosphorylation at the equivalent site by Abl, and may be involved in resistance to drug-induced apoptosis. PMID- 17335006 TI - Identifying long-range structure in the intrinsically unstructured transactivation domain of p53. AB - Paramagnetic relaxation enhancement (PRE) was used to identify a compact dynamic structure for the intrinsically unstructured transactivation domain of the tumor suppressor protein, p53. Our results show that p53 residues essential for binding to the ubiquitin ligase, MDM2, and the 70 kDa subunit of replication protein A, RPA70, are separated by an average distance of 10-15 A. This result suggests that a more extended member of the ensemble must be populated prior to binding either MDM2 or RPA70. We also show that PRE can be used to detect intermolecular distances between p53 and RPA70. PMID- 17335007 TI - Binding of antifusion peptides with HIVgp41 from molecular dynamics simulations: quantitative correlation with experiment. AB - Peptides based on C-terminal regions of the human immunodeficiency virus (HIV) viral protein gp41 represent an important new class of antiviral therapeutics called peptide fusion inhibitors. In this study, computational methods were used to model the binding of six peptides that contain residues that pack into a conserved hydrophobic pocket on HIVgp41, an attractive target site for the development of small molecule inhibitors. Free energies of binding were computed using molecular mechanics Generalized Born surface area (MM-GBSA) methods from molecular dynamics (MD) simulations, which employed either explicit (TIP3P) or continuum Generalized Born (GB) water models and strong correlations between experimental and computational affinities were obtained in both cases. Energy decomposition of the TIP3P-MD results (r2 = 0.75) reveals that variation in experimental affinity is highly correlated with changes in intermolecular van der Waals energies (deltaE(vdw)) on both a local (residue-based, r2 = 0.94) and global (peptide-based, r2 = 0.84) scale. The results show that differential association of C-peptides with HIVgp41 is driven solely by changes within the conserved pocket supporting the hypothesis that this region is an important drug target site. Such strong agreement with experiment is notable given the large size of the ligands (34 amino-acids) relative to the small range of experimental affinities (2 kcal/mol) and demonstrates good sensitivity of this computational method for simulating peptide fusion inhibitors. Finally, inspection of simulation trajectories identified a highly populated pi-type hydrogen bond, which formed between Gln575 on the receptor and the aromatic ring of peptide ligand Phe631, which could have important implications for drug design. PMID- 17335008 TI - Potential role of the cellular allergen stimulation test (CAST) in diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis. AB - Allergic bronchopulmonary aspergillosis (ABPA) is a severe complication in cystic fibrosis (CF), which is difficult to identify because of overlapping unspecific diagnostic features with common CF-manifestations. The cellular allergen stimulation test (CAST) is used in diagnosis of allergic and pseudoallergic reactions. This assay is based on the determination of sulfidoleukotrienes, which are produced by allergen-stimulated basophils in vitro. The potential role of CAST in diagnosis of ABPA was evaluated in this study. The CAST assay was applied in 27 CF-patients including eight subjects with positive clinical and serological signs of ABPA. Additional to the Nelson-criteria for diagnosis of ABPA specific IgE against recombinant Aspergillus antigens (rAsp f 1, 2, 3, 4, and 6) were assessed. The CAST results were positive in all ABPA-patients and in five controls without any sign of ABPA except positive specific IgE against Aspergillus fumigatus (sensitivity of 100%, specificity of 74%). Specific IgE against rAsp f 4 and/or f 6 were positive in six of the eight ABPA-patients, but not in the controls. Positive CAST results, total serum IgE > 500 U/ml and positive IgE antibodies against rAsp f 4 and/or f 6 were only found in ABPA patients (specificity of 100%). The CAST assay on its own includes high sensitivity with lower specificity. For the discrimination of ABPA from sensitization to Aspergillus, the CAST, the highly elevated total serum IgE and rAsp in combination are potential auxiliary diagnostic parameters. PMID- 17335009 TI - Incidental magnetization transfer effects in multislice brain MRI at 3.0T. AB - PURPOSE: To evaluate the effect of incidental magnetization transfer (iMT) in multislice brain imaging at 3.0T. MATERIALS AND METHODS: The contribution of iMT to multislice brain MRI was evaluated at 3.0T. In 10 normal subjects we obtained multislice fast spin-echo (FSE) MR images using a 16-echo pulse train without an off-resonance MT pulse at 3.0T and 1.5T. We quantified the extent of iMT by calculating the iMT ratio (iMTR). RESULTS: We found that the iMT contrast (iMTC) has a greater effect at 3.0T. As the number of slices increased in multislice FSE imaging, the difference between two field strengths became larger. Compared to WM structures, however, the difference in iMT effect between 1.5T and 3.0T was smaller in the case of GM structures. CONCLUSION: The iMTC has a greater effect at 3.0T. The strength of the iMT is different for different tissue types and also varies according to the number of slices used. PMID- 17335010 TI - Disparity between ratios of diameters and blood flows in central pulmonary arteries in postoperative congenital heart disease using MRI. AB - PURPOSE: To compare the relative severity of stenoses of right or left pulmonary arteries with differences in flow to each lung after repair of congenital heart disease (CHD). MATERIALS AND METHODS: A total of 15 patients with postoperative congenital heart disease underwent MRI to evaluate branch pulmonary artery stenoses. Spin-echo images and MR angiography were used to assess morphology, and velocity-encoded cine (VEC) MRI was used to measure flow in the right and left pulmonary arteries. The ratios of the narrowest diameters of the right to left pulmonary arteries (R/L size) and right to left pulmonary arterial flow (R/L flow) were compared using Spearman's correlation. F test was used to assess the significance of the regression coefficients. RESULTS: R/L size ratio varied from 0.50 to 2.66, while the R/L flow ratio varied from 0.36 to 12.02. There was an exponential relationship between R/L size and R/L flow, with r2=0.78 and P=0.001. However, severity of morphologic stenoses was not clinically useful for predicting flow reduction. Prediction residuals ranged from -136% to 54% of the true R/L flow. CONCLUSION: Anatomical evaluation of the pulmonary arteries does not predict accurately differential blood flow in patients with pulmonary stenoses. Therefore, blood flow measurements are essential when considering the need for further surgical or interventional procedures. PMID- 17335011 TI - Internet and written respiratory questionnaires yield equivalent results for adolescents. AB - This study compared results from Internet and written questionnaires about respiratory symptoms in order to find out if both forms of the survey yielded the same answers. One thousand seventy-one students, ages 13 to 17, were asked to complete either an Internet or a written questionnaire. The demographic characteristics of the participants equalled those of the general Dutch adolescent population. Participants were randomly assigned to fill out an electronic or written questionnaire. In addition to eight items from the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, two items on doctor visits (medical attention) regarding asthma or allergic disease during the past 12 months were included. The participation rate was 87%. The Internet version of the questionnaire showed fewer missing answers than the written version, but this was not statistically significant. The respiratory items did not show statistically significant score differences between the Internet and written modes of administration, and there was no visible trend for higher respectively lower scores by either mode of questionnaire administration. From these results, we conclude that respiratory questionnaires may be provided to adolescents electronically rather than on paper, since both approaches yielded equal results. To generalize these findings, we recommend repeated studies in other settings. PMID- 17335012 TI - Flexible fiberoptic bronchoscopy in children with heart diseases: a twelve years experience. AB - In children, cardiac diseases and respiratory disorders are tightly linked entities whose evaluation should be performed integrally. Flexible fiberoptic bronchoscopy (FB) presents a diagnostic and therapeutic role by assessing the airway anatomically, dynamically, and through the performance of several procedures. The present study describes our experience on FB assessment in children with congenital and acquired cardiac diseases, providing a characterization of the principal demographic and clinical features. Records of 72 patients under 14 years (mean age 21 months) with heart diseases, corresponding to 104 FB performed between January 1993 and October 2004 were reviewed. The principal cardiac diseases were left-to-right shunt (51.9%), followed by right-to-left shunt (17.3%) and miscellaneous cardiopathies (8.7%). The main indications for FB assessment were study of atelectasis (35%), stridor (14%), and pneumonia (14%). Airway malacias, as a group, were the commonest finding, represented mainly by left main bronchus malacia (24%). The second most common finding was stenosis by extrinsic compression, and among these, 75% corresponded to left main bronchus compression. Sixteen different types of clinically meaningful utilities were obtained. No mortality was reported and in only one procedure was there a major complication, which was easily managed. We concluded that FB is an important and safe diagnostic-therapeutic tool in the health care of neonates, infants, and children with a variety of cardiac diseases. PMID- 17335013 TI - Catamenial hemoptysis from endobronchial endometriosis in a child with type 1 von Willebrand disease. AB - Catamenial hemoptysis is a rare condition characterized by cyclic pulmonary hemorrhage, synchronous with menses and associated with the presence of intrapulmonary or endobronchial endometrial tissue. Because of the paucity of cases reported in the literature, information regarding the natural history is limited and also the optimal diagnostic workup and management of these patients are not well defined. In this report, we present a case of endobronchial endometriosis in a 12-year-old female diagnosed by bronchoscopy and immunocytochemical assay, associated with type 1 von Willebrand disease. PMID- 17335014 TI - Interpenetrating polymer networks containing gelatin modified with PEGylated RGD and soluble KGF: synthesis, characterization, and application in in vivo critical dermal wound. AB - The purpose of this study was to evaluate the biocompatibility and the efficacy in wound healing of a gelatin-based interpenetrating polymer network (IPN) containing poly(ethylene glycol) (PEG)-ylated RGD and soluble KGF-1 (RGD IPN+KGF). IPNs were applied to full-thickness wounds on a rat model. Wound healing was assessed through histological grading of the host response and percent area contraction at 2 days, 1 week, 2 weeks, and 3 weeks. A control IPN containing unmodified gelatin (unmod-IPN) and a conventional clinical bandage were applied to similar wounds and also evaluated. During the first week of healing, the unmod-IPN and conventional dressing wound showed a greater amount of contraction than that of RGD-IPN+KGF. However, by 3 weeks the extent of wound contraction was comparable between treatments. The RGD-IPN+KGF treated wound demonstrated lower macrophage and fibroblast densities at 3 weeks as compared to unmod-IPN treated wounds. RGD-IPN+KGF acted as a tissue scaffold while preventing the entry of foreign bodies, advantages not seen with the conventional dressing. The extent of cellularity and extracellular matrix organization was higher for wounds healed with RGD-IPN+KGF than those healed with unmod-IPN. These results indicate that both soluble and immobilized bioactive factors can be incorporated into our IPN platform to enhance the rate and the quality of dermal wound healing. PMID- 17335015 TI - Evaluation of laser spallation as a technique for measurement of cell adhesion strength. AB - Cell adhesion to material surfaces is one of the fundamental phenomena of cellular response to implanted devices. Controlling the strength, dynamics, and mechanics of cell adhesion offer opportunities for designing novel biomaterials for tissue engineering and biotechnology. Many techniques have been developed for the purpose of quantifying various types of cell-biomaterial interaction. One method to evaluate cell affinity for a biomaterial is to measure the stress required to remove adherent cells from the material. This study investigates the possibility of using laser spallation, a technique previously developed for measuring the tensile strength of thin film interfaces, for evaluation of initial cell attachment strength. MC3T3-E1 preosteoblasts were cultured on fibronectin coated polystyrene, a surface known to engage cells in receptor mediated adhesion, and untreated polystyrene, which elicit nonspecific adhesion mechanisms during early stages of cell attachment. The laser spallation technique effectively detached cells from polymer substrates and also distinguished relative cell adhesion strengths to surfaces with known differences in cell binding affinities. Scanning electron micrographs determined that cell detachment resulting from laser spallation left a cleaner surface than jet impingement, possibly suggesting a more complete detachment mechanism. Absolute values of adhesion strengths determined by laser spallation were significantly higher than those found using jet impingement, a previously reported hydrodynamic technique. PMID- 17335016 TI - Surface modification and characterization of chitosan or PLGA membrane with laminin by chemical and oxygen plasma treatment for neural regeneration. AB - Attachment to and proliferation on the substrate are deemed important considerations when Schwann cells (SCs) are to be seeded in synthetic nerve grafts. Good attachment is a prerequisite for the SCs to survive. Fast proliferation will yield large numbers of SCs in a short time, which appears to be promising for stimulating peripheral nerve regeneration. However, surface properties are the dominating factor in influencing the interactions between cells and synthetic nerve grafts. The aim of this study was to investigate the surface effects of laminin modified PLGA and chitosan membranes after chemical method and plasma treatment. Laminin, the extracellular matrix protein, is a permissive protein for SCs adhesion used in neural regeneration. The surface properties of laminin modified membranes were assayed by BCA, FTIR and XPS analysis. Results showed that laminin was covalently bonded onto the surface of both PLGA and chitosan membranes either by chemical method or by oxygen plasma treatment. The cell affinity of the laminin modified membranes was verified by Schwann cells culturing. Our results also indicate that oxygen plasma is indeed a better method to incorporate laminin onto the surface of membrane. Laminin modified chitosan membrane significantly increases SCs attachment and affinity for directing peripheral nerve regeneration. PMID- 17335017 TI - Mechanism of degradation of AgCl coating on biopotential sensors. AB - AgCl coated Ag foil has been widely used as the biopotential sensor to diagnose problems of the human heart. Evidence shows that quality of AgCl on the electrode could experience degradation during the process of long-term monitoring for irregular activities of the heart. To study the degradation of AgCl/Ag electrode, new and used electrodes were collected. Electrochemical tests such as open circuit potential (OCP), cathodic stripping, electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and X-ray mapping of elemental distribution were applied to understand the electrochemical properties of the sensors during the progress of degradation. Results revealed that OCP values shift from positive potential of new sensor to negative potential of used sensor (OCP(new): +30 mV; OCP(used): -300 mV, p < 0.05) and a significant difference in impedance (Impedance(new): 3000 Omega; Impedance(used): 1 MOmega, p < 0.05). Ratio of the average AgCl thickness on good and bad eletrocardiographic (ECG or EKG) electrodes is 4.83 (p < 0.05). Simulated degradation by exposing the biosensor to deaerated sweat solution and by cathodic stripping of AgCl proposed that the degradation occurs by cathodic reduction of AgCl due to the presence of hydrogen ions in the low pH value of human sweat under deaerated condition. PMID- 17335018 TI - Diffusion-weighted MRI (DWI) in the oncology patient: value of breathhold DWI compared to unenhanced and gadolinium-enhanced MRI. AB - PURPOSE: To evaluate the feasibility and added value of single breathhold diffusion-weighted (DW) imaging (DWI) in oncology patients undergoing abdominal MRI. MATERIALS AND METHODS: A total of 169 patients with malignancy underwent abdominal MRI at 1.5T, including T1-weighted (T1W), T2-weighted (T2W), and dynamic gadolinium-enhanced imaging. Axial DWI was performed with a single-shot spin-echo (SE) echo-planar imaging (EPI) sequence using a b-value of 500 seconds/mm2. A total of 24 slices were obtained during a 20-second breathhold. Two observers reviewed the conventional MR images for tumor. Next, the DW images were reviewed for additional tumor not depicted on conventional MR images RESULTS: For the 169 patients, additional tumors were noted on the DW images in 77 (0.46) for observer 1 and 67 (0.40) for observer 2. For observer 1 the additional tumor included lymphadenopathy (47), peritoneal metastases (15), renal (1), liver (12), and osseous (2), while for observer 2 the corresponding values were lymphadenopathy (40), peritoneal (12), renal (1), liver (6), osseous (4), and gastrointestinal (1). The DW images resolved as benign findings noted on the conventional MR images in three patients for observer 1 and four patients for observer 2. The conventional MR exam was entirely normal while the DW images showed tumor in 12 (0.07) patients for observer 1 and 10 (0.06) patients for observer 2. CONCLUSION: DWI is feasible in a single breathhold and provides additional clinically important information in oncology patients when added to routine abdominal MR sequences. PMID- 17335019 TI - Characterization of holmium loaded alginate microspheres for multimodality imaging and therapeutic applications. AB - In this paper the preparation and characterization of holmium-loaded alginate microspheres is described. The rapid development of medical imaging techniques offers new opportunities for the visualisation of (drug-loaded) microparticles. Therefore, suitable imaging agents have to be incorporated into these particles. For this reason, the element holmium was used in this study in order to utilize its unique imaging characteristics. The paramagnetic behaviour of this element allows visualisation with MRI and holmium can also be neutron-activated resulting in the emission of gamma-radiation, allowing visualisation with gamma cameras, and beta-radiation, suitable for therapeutic applications. Almost monodisperse alginate microspheres were obtained by JetCutter technology where alginate droplets of a uniform size were hardened in an aqueous holmium chloride solution. Ho(3+) binds via electrostatic interactions to the carboxylate groups of the alginate polymer and as a result alginate microspheres loaded with holmium were obtained. The microspheres had a mean size of 159 microm and a holmium loading of 1.3 +/- 0.1% (w/w) (corresponding with a holmium content based on dry alginate of 18.3 +/- 0.3% (w/w)). The binding capacity of the alginate polymer for Ho(3+) (expressed in molar amounts) is equal to that for Ca(2+), which is commonly used for the hardening of alginate. This indicates that Ho(3+) has the same binding affinity as Ca(2+). In line herewith, dynamic mechanical analyses demonstrated that alginate gels hardened with Ca(2+) or Ho(3+) had similar viscoelastic properties. The MRI relaxation properties of the microspheres were determined by a MRI phantom experiment, demonstrating a strong R(2)* effect of the particles. Alginate microspheres could also be labelled with radioactive holmium by adding holmium-166 to alginate microspheres, previously hardened with calcium (labelling efficiency 96%). The labelled microspheres had a high radiochemical stability (94% after 48 h incubation in human serum), allowing therapeutic applications for treatment of cancer. The potential in vivo application of the microspheres for a MR-guided renal embolization procedure was illustrated by selective administration of microspheres to the left kidney of a pig. Anatomic MR-imaging showed the presence of holmium-loaded microspheres in the kidney. In conclusion, this study demonstrates that the incorporation of holmium into alginate microspheres allows their visualisation with a gamma camera and MRI. Holmium loaded alginate microspheres can be used therapeutically for embolization and, when radioactive, for local radiotherapy of tumours. PMID- 17335020 TI - Antibacterial and osteogenic properties of silver-containing hydroxyapatite coatings produced using a sol gel process. AB - Since bacterial infection is a rising complication following the wide use of implant, there is considerable attention on the effect of implant surface properties on bacterial adhesion. In this study, the effect of silver (Ag) doped hydroxyapatite (HA) coatings on initial antibacterial adhesion and osteoblast cell proliferation and differentiation was investigated. Using a sol-gel process, HA coatings doped with 1 wt % AgNO(3) (AgHA1.0) and 1.5 wt % Ag (AgHA1.5) were prepared. Coated surfaces were characterized using X-ray diffraction (XRD) and contact angles measurements. The initial bacteria adhesion was evaluated using a RP12 strain of Staphylococcus epidermidis (ATCC 35984) and the Cowan I strain of Staphylococcus aureus, whereas osteoblast proliferation and differentiation were evaluated using human embryonic palatal mesenchyme cells (HEPM), an osteoblast precursor cell line. In this study, XRD analysis of all surfaces indicated peaks corresponding to HA. Contact angles for AgHA surfaces were observed to be significantly lower when compared to HA surfaces. In vitro initial bacterial adhesion study indicated a significantly reduced number of S. epidermidis and S. aureus on AgHA surfaces when compared to HA surface. The use of HEPM cells indicated no significant difference in double-stranded DNA (dsDNA) production between all surfaces. Additionally, no differences in alkaline phosphatase specific activity were observed between HA and AgHA1.0 surfaces. Overall, it was concluded that AgHA1.0 has the similar biological activity as HA, with respect to bone cell proliferation and differentiation. In addition, the AgHA1.0 was also concluded to have the ability to minimize the initial bacteria adhesion. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007. PMID- 17335021 TI - Anodized titanium and stainless steel in contact with CFRP: an electrochemical approach considering galvanic corrosion. AB - The combination of different materials in an implant gives the opportunity to better fulfill the requirements that are needed to improve the healing process. However, using different materials increases the risk of galvanic coupling corrosion. In this study, coupling effects of gold-anodized titanium, stainless steel for biomedical applications, carbon fiber reinforced polyetheretherketone (CFRP), and CFRP containing tantalum fibers are investigated electrochemically and by long-term immersion experiments in simulated body fluid (SBF). Potentiodynamic polarization experiments (i/E curves) and electrochemical impedance spectroscopy (EIS) of the separated materials showed a passive behavior of the metallic samples. Anodized titanium showed no corrosion attacks, whereas stainless steel is highly susceptibility for localized corrosion. On the other side, an active dissolution behavior of both of the CFRPs in the given environment could be determined, leading to delaminating of the carbon fibers from the matrix. Long-term immersion experiments were carried out using a set-up especially developed to simulate coupling conditions of a point contact fixator system (PC-Fix) in a biological environment. Electrochemical data were acquired in situ during the whole immersion time. The results of the immersion experiments correlate with the findings of the electrochemical investigation. Localized corrosion attacks were found on stainless steel, whereas anodized titanium showed no corrosion attacks. No significant differences between the two CFRP types could be found. Galvanic coupling corrosion in combination with crevice conditions and possible corrosion mechanisms are discussed. PMID- 17335022 TI - Rapid aqueous photo-polymerization route to polymer and polymer-composite hydrogel 3D inverted colloidal crystal scaffolds. AB - Successful regeneration of biological tissues in vitro requires the utilization of three-dimensional (3D) scaffolds that provide a near natural microenvironment for progenitor cells to grow, interact, replicate, and differentiate to form target tissues. In this work, a rapid aqueous photo-polymerization route was developed toward the fabrication of a variety of polymer hydrogel 3D inverted colloidal crystal (ICC) scaffolds having different physical and chemical properties. To demonstrate the versatility of this technique, a variety of polymer hydrogel ICC scaffolds were prepared, including (1) polyacrylamide (pAAM) scaffolds, (2) poly(2-hydroxyethyl methacrylate) (pHEMA) scaffolds, (3) poly(2 hydroxyethyl acrylate) (pHEA) scaffolds, and composite scaffolds including (4) pAAM-pHEMA scaffolds, (5) pHEMA-pMAETAC [poly(2-methacryloyloxy) trimethyl ammonium] scaffolds, and (6) pHEA-pMEATAC scaffolds. Templates for scaffolds incorporated both uniform sized (104 microm diameter) and nonuniform sized (100 +/- 20 microm diameter) closely packed noncrosslinked poly(methyl methacrylate) beads. Human bone marrow stromal HS-5 cells were cultured on the six different types of scaffolds to demonstrate biocompatibility. Experimental results show that cells can remain viable in these scaffolds for at least 5 weeks. Of the six scaffolds, maximal cell adhesion and proliferation are obtained on the positively charged composite hydrogel pHEMA-pMEATAC and pHEA-pMAETAC scaffolds. PMID- 17335023 TI - Hemocompatibility evaluation of poly(diol citrate) in vitro for vascular tissue engineering. AB - One of the ongoing challenges in tissue engineering is the synthesis of a hemocompatible vascular graft. Specifically, the material used in the construct should have antithrombogenic properties and support the growth of vascular cells. Our laboratory has designed a novel biodegradable, elastomeric copolymer, poly(1,8-octanediol citrate) (POC), with mechanical and degradation properties suitable for vascular tissue engineering. The hemocompatibility of POC in vitro and its ability to support the attachment and differentiation of human aortic endothelial cell (HAEC) was assessed. The thrombogenicity and inflammatory potential of POC were assessed relative to poly(l-lactide-co-glycolide) and expanded poly(tetrafluoroethylene), as they have been used in FDA-approved devices for blood contact. Specifically, platelet aggregation and activation, protein adsorption, plasma clotting, and hemolysis were investigated. To assess the inflammatory potential of POC, the release of IL-1beta and TNF-alpha from THP 1 cells was measured. The cell compatibility of POC was assessed by confirming HAEC differentiation and attachment under flow conditions. POC exhibited decreased platelet adhesion and clotting relative to control materials. Hemolysis was negligible and protein adsorption was comparable to reference materials. IL 1beta and TNF-alpha release from THP-1 cells was comparable among all materials tested, suggesting minimal inflammatory potential. POC supported HAEC differentiation and attachment without any premodification of the surface. The results described herein are encouraging and suggest that POC is hemocompatible and an adequate candidate biomaterial for in vivo vascular tissue engineering. PMID- 17335024 TI - 3D excretory MR urography: improved image quality with intravenous saline and diuretic administration. AB - PURPOSE: To assess the effect of diuretic administration on the image quality of excretory magnetic resonance urography (MRU) obtained following intravenous hydration, and to determine whether intravenous hydration alone is sufficient to produce diagnostic quality studies of nondilated upper tracts. MATERIALS AND METHODS: A total of 22 patients with nondilated upper tracts were evaluated with contrast-enhanced MRU. All patients received 250 mL of saline intravenously immediately prior to the examination. A total of 11 patients received 10-20 mg furosemide in addition to saline. Imaging was performed with a three-dimensional (3D) and two-dimensional (2D) breathhold spoiled gradient-echo sequences. Excretory MRU images were acquired five minutes after the administration of 0.1 mmol/kg gadolinium and were independently reviewed by two radiologists, who were blinded to the MRU technique. Readers evaluated the calyces, renal pelvis, and ureters qualitatively for degree of opacification, distention, and artifacts on a four-point scale. Statistical analysis was performed using a permutation test. RESULTS: There was no significant disagreement between the two readers (P=0.14). Furosemide resulted in significant improvement in calyceal and renal pelvis distention (P<0.005), and significant artifact reduction in all upper tract segments (P<0.001) compared to the effect of saline alone. CONCLUSION: Intravenous furosemide significantly improves the image quality of excretory MRU studies obtained following intravenous hydration. Intravenous saline alone is insufficient to produce diagnostic quality studies of the non-dilated upper tracts. PMID- 17335025 TI - What causes diminished corticomedullary differentiation in renal insufficiency? AB - PURPOSE: To investigate whether the loss of corticomedullary differentiation (CMD) on T1-weighted MR images due to renal insufficiency can be attributed to changes in T1 values of the cortex, medulla, or both. MATERIALS AND METHODS: Study subjects included 10 patients (serum creatinine range 0.6-3.0 mg/dL) referred for suspected renovascular disease who underwent 99mTc-diethylene triamine pentaacetic acid (DTPA) renography to determine single kidney glomerular filtration rate (SKGFR) and same-day MRI, which included T1 measurements and unenhanced T1-weighted gradient echo imaging. Corticomedullary differentiation on T1-weighted images was assessed qualitatively and quantitatively. RESULTS: SKGFR values ranged from 3.5 to 89.4 mL/minute based on radionuclide studies. T1 relaxation times of the medulla exceeded those of renal cortex by 147.9+/-176.0 msec (mean+/-standard deviation [SD]). Regression analysis showed a negative correlation between cortex T1 and SKGFR (r=-0.5; P=0.03), whereas there was no significant correlation between medullary T1 and SKGFR. The difference between medullary and cortical T1s correlated significantly with SKGFR (r=0.58; P<0.01). In all five kidneys with a corticomedullary contrast-to-noise ratio (CNR)<5.0 on T1-weighted images, SKGFR was less than 20 mL/minute. CONCLUSION: In our subject population, loss of CMD with decreasing SKGFR can be attributed primarily to an increased T1 relaxation time of the cortex. Medullary T1 values vary but do not appear to correlate with degree of renal insufficiency. PMID- 17335026 TI - Pulmonary agenesis. PMID- 17335027 TI - Polymers with tunable toxicity: a reference scale for cytotoxicity testing of biomaterial surfaces. AB - A series of copolymers, with varying ratio di-methylamino-ethylmethacrylate (DMAEMA) and methyl-methacrylate (MMA), was designed as a potential scale for cytotoxicity. These copolymers were characterized for toxicity of their surface. The surfaces of washed copolymers display increasing toxicity with increasing DMAEMA content. The toxicity was observed for three different cell-types, namely mouse fibroblasts, human endothelial cells and human osteoblast-like cells. With an increasing toxic surface, cell growth was inhibited as was indicated by the proliferation marker Ki-67. Staining for F-actin revealed that with increasing DMAEMA, cells adopted a more and more round morphology, resulting in decreased surface-contact area. Immuno-staining for phospho-tyrosine or vinculin demonstrated gradual loss of focal adhesions on increasingly toxic surfaces. Surprisingly loss of focal adhesions coincided with an increase in paxillin and vinculin protein, indicating cells try compensating for loss of adhesion. This series of copolymers may have potential as a cytotoxicity scale. They provoke cellular responses ranging from highly toxic to completely non-toxic, with some showing intermediate toxicity. PMID- 17335028 TI - Encapsulation and osteoinduction of human periodontal ligament fibroblasts in chitosan-hydroxyapatite microspheres. AB - Periodontal ligament cells play a crucial role in the regeneration of periodontal tissues and an undifferentiated mesenchymal cell subset is thought to exist within this population. The aim of this study was to assess the osteogenic differentiation potential of human periodontal ligament fibroblasts (hPDLFs) in three dimensional (3D)-osteogenic culture environment following encapsulation in chitosan-hydroxyapatite (C/HA) microspheres with the size range of 350-450 microm. Human PDLF cultures were established and three experimental groups were formed: (i) two-dimensional (2D)-culture as single cell monolayer, (ii) 3D-static culture of C/HA encapsulated hPDLFs, and (iii) 3D-dynamic culture of C/HA encapsulated hPDLFs in a rotating wall vessel bioreactor. The cells were cultured in standard culture medium supplemented with beta-glycerophosphate, dexamethasone, and ascorbic acid. After 21 days, immunohistochemistry was performed using antibodies against osteonectin, osteopontin, bone-sialoprotein, and osteocalcin as osteogenic differentiation markers. Phase-contrast and scanning electron microscopy observations were used for histological and morphological evaluation. The combined effects of osteoinductive medium and HA containing composite microsphere material on encapsulated hPDLFs resulted in the transformation of a considerable portion of the cells into osteoblastic lineage at the end of the experiments. Results demonstrate the ability of hPDLFs to undergo osteogenic differentiation upon induction in vitro, both under 2D and 3D culture conditions. C/HA microspheres in microgravity bioreactor may serve as a suitable 3D environment to support the osteogenic differentiation of human PDLFs, in vitro. PMID- 17335029 TI - Effect of solvent content on resin hybridization in wet dentin bonding. AB - With wet bonding techniques, the channels between the demineralized dentin collagen fibrils are filled with debris, solvent, and water. Commercial adhesives include solvents such as ethanol or acetone to facilitate resin-infiltration into this wet substrate. Under in vivo conditions, the solvent may be diluted because of repeated exposure of the material to the atmosphere, or concentrated because of separation of the bonding liquids into layers within the bottle. The purpose of this study was to investigate the effect of different concentrations of ethanol (10-50%) on infiltration of the adhesive resin and collagen fibril encapsulation in the adhesive/dentin interface using light microscopy, micro Raman spectroscopy, and scanning electron microscopy. The results indicated that under wet bonding conditions the hybridization process was highly sensitive to the initial solvent concentration in the adhesive system. The staining and scanning electron microscopy results showed that the quality of the interfacial hybrid layer was poor at the lower (10%) or higher (50%) ethanol content. Micro Raman analysis indicated that there was a distinct difference in the degree of adhesive penetration among adhesives containing different concentrations of ethanol. Adhesives containing 10 or 50% ethanol did not realize effective penetration; the penetration of the adhesive monomers increased dramatically when the initial ethanol content was 30%. The amount of solvents are essential for achieving effective bonding to dentin. PMID- 17335030 TI - Surface engineering of titanium thin films with silk fibroin via layer-by-layer technique and its effects on osteoblast growth behavior. AB - The objective of the present study was to surface modify the titanium thin films to improve its biocompatibility. A layer-by-layer (LBL) self-assembly technique, based on the electrostatic interactions mediated adsorption of chitosan (Chi) and silk fibroin (SF), was used leading to the formation of multilayers on the titanium thin film surfaces. The surface chemistry and wettability of LBL films were investigated by X-ray photoelectron spectroscopy (XPS), water contact angle measurement, and atomic force microscopy, respectively. XPS and contact angle measurement results indicated that a full SF/Chi pair film was formed after the deposition layers of PEI/(SF/Chi)(2) on the titanium film surfaces. The topographies of multilayered films were directly related to the corresponding outmost layer components. The build-up of such SF/Chi pair films on titanium films may in turn affect the biocompatibility of the modified titanium films. Therefore, an in vitro investigation was performed to confirm this hypothesis. Cell proliferation, cell viability, DNA synthesis as well as differentiation function (alkaline phosphatase) of osteoblasts on LBL-modified titanium films and control samples were investigated, respectively. Osteoblasts cultured on modified titanium films was found to be higher proliferation tendency than that on control (p < 0.05). Cell viability, alkaline phosphatase as well as DNA synthesis measurement indicated that osteoblasts on LBL-modified films were greater (p < 0.05 or p < 0.01) than the control, respectively. These results suggest that surface engineering of titanium was successfully achieved via LBL deposition of Chi/SF pairs, and enhanced its cell biocompatibility. The approach presented in the study may be exploited as an efficient alternative for surface engineering of titanium-based implants. PMID- 17335031 TI - Comparison between sol-gel-derived anatase- and rutile-structured TiO2 coatings in soft-tissue environment. AB - The bioactivity of the surface reactive TiO(2) coatings for medical implants can be locally modified by CO(2) laser processing to match with the properties of surrounding tissues. The TiO(2) coatings heat-treated at 500 degrees C exhibit in vitro bioactivity. With further CO(2) laser treatment they exhibit enhanced in vitro bioactivity. The aim of this in vivo study was to compare the performance of heat-treated anatase-structured TiO(2) coatings with preheat-treated and CO(2) laser-treated rutile-structured coatings in terms of their ability to attach soft connective tissues. The coatings were characterized with TF-XRD and AFM. TiO(2) coated discs were implanted in rats. The samples were analyzed with routine histology, SEM-EDS, and TEM. In both groups, already at 3 days, soft connective tissues were in immediate contact with the surface. No thick crystalline CaP layer was detected by SEM-EDS, but a thin amorphous CaP layer was detected by XPS. No gap between the cell membrane and the coating could be observed in TEM pictures. No differences were observed between the anatase- and rutile-structured coatings in terms of tissue responses. Further studies are needed to verify if the tissues are adherent to the surface of the implant. PMID- 17335032 TI - Biochemical composition of the superficial layer of articular cartilage. AB - To gain more information on the mechanism of lubrication in articular joints, the superficial layer of bovine articular cartilage was mechanically removed in a sheet of ice that formed on freezing the cartilage. Freeze-dried samples contained low concentrations of chondroitin sulphate and protein. Analysis of the protein by SDS PAGE showed that the composition of the sample was comparable to that of synovial fluid (SF). Attenuated total reflection infrared (ATR-IR) spectroscopy of the dried residue indicated that the sample contained mostly hyaluronan. Moreover, ATR-IR spectroscopy of the upper layer of the superficial layer, adsorbed onto silicon, showed the presence of phospholipids. A gel could be formed by mixing hyaluronan and phosphatidylcholine in water with mechanical properties similar to those of the superficial layer on cartilage. Much like the superficial layer of natural cartilage, the surface of this gel became hydrophobic on drying out. Thus, it is proposed that the superficial layer forms from hyaluronan and phospholipids, which associate by hydrophobic interactions between the alkyl chains of the phospholipids and the hydrophobic faces of the disaccharide units in hyaluronan. This layer is permeable to material from the SF and the cartilage, as shown by the presence of SF proteins and chondroitin sulphate. As the cartilage dries out after removal from the joint, the phospholipids migrate towards the surface of the superficial layer to reduce the surface tension. It is also proposed that the highly efficient lubrication in articular joints can, at least in part, be attributed to the ability of the superficial layer to adsorb and hold water on the cartilage surface, thus creating a highly viscous boundary protection. PMID- 17335033 TI - Surface structure and apatite-forming ability of polyethylene substrates irradiated by oxygen cluster ion beams. AB - Polyethylene (PE) substrates were irradiated at a dose of 1 x 10(15) ions/cm(2) by the simultaneous use of oxygen (O(2)) cluster and monomer ion beams. The acceleration voltage for the ion beams was varied from 3 to 9 kV. Unirradiated and irradiated PE substrates were soaked for 7 days in a metastable calcium phosphate solution (1.5SBF) that had 1.5 times the ion concentrations of a normal simulated body fluid. The irradiated PE substrates formed apatite on their surfaces, irrespective of the acceleration voltage, whereas unirradiated substrates did not form apatite. This is attributed to the formation of functional groups that are effective for apatite nucleation, such as --COOH groups, on the substrate surface by the simultaneous use of O(2) cluster and monomer ion beams. The apatite-forming ability of the irradiated PE substrates was improved greatly by a subsequent CaCl(2) solution treatment. This suggests that Ca(2+) ions introduced on the substrate surface by the CaCl(2) solution treatment accelerated the apatite nucleation. It is concluded that apatite forming ability can be induced on the surface of PE by the simultaneous use of O(2) cluster and monomer ion beams. PMID- 17335034 TI - The interaction between hydrolytic and oxidative pathways in macrophage-mediated polyurethane degradation. AB - Although relatively resistant to oxidation, polycarbonate-based polyurethanes (PCNUs) are degraded by monocyte-derived macrophages (MDM) by a co-mediated mechanism involving both hydrolytic and oxidative pathways. Since a previous study showed that PCNU pretreatment with H(2)O(2) modulated degradation by esterases, human MDM were used to further elucidate this dual pathway mechanism of degradation for (14)C-radiolabeled PCNUs (synthesized with 1,6-hexane diisocyanate:polycarbonatediol: butanediol with different stoichiometry (HDI431 and HDI321) or another diisocyanate 4,4'-methylene bisphenyl diisocyanate (MDI321)). Scanning electron microscopy of PCNU slips pretreated with 20% H(2)O(2) showed that HDI431 had visible holes with more radiolabel release than from the other PCNUs. When MDM were seeded on H(2)O(2)-treated PCNUs, degradation of HDI321 and MDI321, but not HDI431 was decreased. Esterase activity was inhibited in MDM on all surfaces except MDI321, whereas inhibition of acid phosphatase occurred on all surfaces. The material surface itself, induced H(2)O(2) release from live MDM, with more H(2)O(2) elicited by phorbol myristate acetate treated MDM when cultured on HDI431 but not the other materials. H(2)O(2) pretreatment affected cell function by chemically altering the material surface and MDM-mediated degradation, known to be dependent on surface chemistry. The findings highlight that both oxidative and hydrolytic mechanisms need to be understood in order to tailor material chemistry to produce desired cell responses for in vivo applications. PMID- 17335035 TI - Novel low temperature setting nanocrystalline calcium phosphate cements for bone repair: osteoblast cellular response and gene expression studies. AB - Low temperature setting calcium phosphate cements (CPC) formed from reactive calcium phosphate precursors are receiving great attention in the fields of orthopaedics and tissue engineering. The purpose of this study was to evaluate the mechanical properties and osteocompatibility of a novel calcium deficient hydroxyapatite (CDSHA) with a Ca/P ratio of 1.6 developed in our laboratories and compare it to a previously developed calcium deficient hydroxyapatite (CDHA) with a Ca/P ratio of 1.5. The results demonstrated that the calcium-deficient hydroxyapatites (HA) formed from the CPCs were similar to biological HA at physiological temperature and the elastic moduli of CDHA and CDSHA were found to be 174.42 +/- 20.41 MPa (p < 0.05) and 115.86 +/- 24.8 MPa (p < 0.05), respectively. The surface morphologies of the two calcium deficient HA's formed were identical with a micro/nano porous structure as evidenced from SEM. The cellular proliferation on CDHA, and CDSHA, was comparable to the control, tissue culture polystyrene (TCPS) (p < 0.05). Alkaline phosphatase activity was significantly elevated on CDHA and CDSHA matrices at early time points when compared with the control (TCPS) (p < 0.05). Osteoblast cells gene expression on CDHA, and CDSHA showed type I collagen, alkaline phosphatase, osteocalcin, and osteopontin activity at both 7 and 14 days of culture. Thus, novel calcium deficient HAs, CDHA, and CDSHA formed at low temperature are promising candidates for orthopaedic applications based on their ability to promote osteoblast cell adhesion and gene expression in vitro. PMID- 17335036 TI - Integrin-linked kinase production prevents anoikis in human mesenchymal stem cells. AB - Human mesenchymal stem cells (hMSCs) were infected with an adenovirus expressing integrin-linked kinase (ILK) to understand the role of cell-ECM signal transduction cascades in suppressing anoikis. Survivability of ILK-infected hMSCs encapsulated in poly(ethylene glycol) (PEG) hydrogels, an anoikis-inducing environment, was sustained at 90% over 7 weeks, and survival was attributed to increased protein kinase B (PKB/Akt) activation. hMSCs encapsulated in RGD modified hydrogels induced an upregulation in ILK production, PKB/Akt activation, and subsequent survival to the same extent of ILK-infected, encapsulated hMSCs. As negative controls, encapsulated hMSCs were infected with cyclization recombinase (a protein not associated with cell survival)-expressing virus, and uninfected hMSCs exhibited very little ILK production, PKB/Akt activation, and survival ( approximately 55% after 7 weeks). As a measure of cell-matrix interactions, vinculin was also quantified for the encapsulated hMSCs and found to be 30-fold greater for cells encapsulated in RGD-modified hydrogels and fivefold greater for ILK-infected hMSCs than controls, indicating that cell material interactions are inducing the cell survivability of hMSCs encapsulated in RGD-modified hydrogels. In sum, ILK infection can support cell survival in the absence of matrix interactions and enable fundamental studies of three dimensional cell function in response to extrinsic signals, independently of matrix-ligand interactions. PMID- 17335037 TI - Localization of the transcriptional coactivator PGC-1alpha to GABAergic neurons during maturation of the rat brain. AB - The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) can activate a number of transcription factors to regulate mitochondrial biogenesis and cell-specific responses to cold, fasting, and exercise. Recent studies indicate that PGC-1alpha knockout mice exhibit behavioral abnormalities and progressive vacuolization in various brain regions. To investigate the roles for PGC-1alpha in the nervous system, we evaluated the temporal and cell-specific expression of PGC-1alpha in the normal developing rat brain. Western blot of whole brain homogenates with a PGC-1alpha-specific antibody revealed that PGC-1alpha protein was most abundant in the embryonic and early postnatal forebrain and cerebellum. Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we determined that PGC-1alpha mRNA expression increased most markedly between postnatal days 3 (P3) and 14 in the cortex, striatum, and hippocampus. Immunohistochemical and immunofluorescence analyses of brain tissue indicated that while PGC-1alpha was found in most neuronal populations from embryonic day 15 to P3, it was specifically concentrated in GABAergic populations from P3 to adulthood. Interestingly, PGC 1alpha colocalized with the developmentally regulated chemoattractant reelin in the cortex and hippocampus, and the survival-promoting transcription factor myocyte enhancing factor 2 was highly concentrated in GABAergic populations in the striatum and cerebellum at times of PGC-1alpha expression. These results implicate PGC-1alpha as a regulator of metabolism and/or survival in GABAergic neurons during a phase of mitochondrial and synaptic changes in the developing brain and suggest that PGC-1alpha may be a good target for increasing metabolism in GABAergic populations in neurodevelopmental and neurodegenerative disorders. PMID- 17335038 TI - Two types of Drosophila R7 photoreceptor cells are arranged randomly: a model for stochastic cell-fate determination. AB - The R7 photoreceptor cells of the Drosophila retina are ultraviolet sensitive and are thought to mediate color discrimination and polarized light detection. In addition, there is growing evidence that the color sensitivity of the R8 cell within an individual ommatidium is regulated by a genetic switch that depends on the type of R7 cell adjacent to it. Here we examine the organization of the two major types of R7 cells by three different rigorous statistical methods and present evidence that they are arranged randomly and independently. First, we performed L-function analyses to test whether the organization of R7 cells (and the relationship between them) is regular, clustered, or completely spatially random. Next, we used generalized linear mixed models to test whether the proportion of R7 cell neighbors differs from their prevalence within the eye as a whole. Finally, we conducted a series of simulations to test whether the proportion of R7 cell neighbors differs from that in a random simulation. In each case, we found evidence that the organization of the two types of R7 cells is random and independent, suggesting that R7 cells in neighboring ommatidia are unlikely to interact and influence each other's identity and may be determined stochastically in a cell-autonomous manner. Compared with traditional lineage or inductive mechanisms, this may represent a novel mechanism of cell fate determination based on noisy or stochastic gene expression in which the differentiation of an individual R7 cell is a random event but the proportions of R7 cell subtypes are regulated. PMID- 17335039 TI - Time-resolved three-dimensional contrast-enhanced magnetic resonance angiography in patients who have undergone a Fontan operation or bidirectional cavopulmonary connection: initial experience. AB - PURPOSE: To evaluate the usefulness of time-resolved three-dimensional (3D) magnetic resonance angiography (MRA) using diluted contrast agent (CA) in patients who had undergone a Fontan operation or bidirectional cavopulmonary connection (BCPC). MATERIALS AND METHODS: Time-resolved 3D MRA (10 dynamic data sets, two seconds per dynamic data set) using parallel imaging and keyhole data sampling was performed on 15 patients (median age=10 years, range=1-20 years) who had undergone a Fontan operation (N=11) or BCPC (N=4). Diluted gadolinium (Gd) contrast agent (CA) was intravenously injected into the arm and/or leg veins. The flow dynamics and morphology of pulmonary circulation, and lung perfusion were assessed. RESULTS: Preferential or balanced pulmonary blood flow from each systemic vein was visualized on time-resolved 3D MRA in all patients. In addition, occlusion/stenosis of the central thoracic vein (N=4) and pulmonary artery (N=6), systemic venous (N=5) and arterial (N=6) collaterals, and lung perfusion defect (N=4) were identified. Persistent hepatic venous plexus, pulmonary arteriovenous malformation, and axillary arteriovenous fistula were delineated in three patients, respectively. CONCLUSION: Time-resolved 3D MRA with diluted CA is useful for evaluating patients who have undergone a Fontan operation or BCPC because it can reveal the flow dynamics and morphology of pulmonary circulation, and lung perfusion status. PMID- 17335040 TI - Superparamagnetic iron oxide (SPIO)-enhanced liver MRI with ferucarbotran: efficacy for characterization of focal liver lesions. AB - PURPOSE: To evaluate the efficacy of ferucarbotran in T2-weighted (T2W) fast spin echo (FSE) and T2*W gradient-echo (GRE) sequences for characterizing focal liver lesions. MATERIALS AND METHODS: In 68 patients, 46 malignant and 22 benign focal liver lesions were evaluated. Precontrast (NCE) T2W FSE images and contrast enhanced (CE) T2W FSE and T2*W GRE images were obtained on a 1.5T MR system. Based on signal intensity (SI) measurements in focal lesions and liver parenchyma, the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for all sequences. The percentage of SI loss (PSIL) in focal lesions after contrast agent (CA) application was calculated for the T2W FSE sequence. Qualitative analyses were performed to assess image quality and lesion conspicuity obtained with the CE-T2W FSE and CE-T2*W GRE sequences. RESULTS: The mean PSIL was higher in solid benign lesions than in malignant lesions (39.6% vs. 3.2%, P<0.05). With a threshold PSIL of 25%, the sensitivity and specificity for characterizing malignant lesions were 97.8% and 92.9%, respectively. The mean CNR of the malignant lesions was higher in the CE-T2*W sequence than in the CE- and NCE-T2W FSE sequences (29.9 vs. 22.7 (P<0.01) vs. 12.8 (P<0.01)). CE-T2*W images showed a superior image quality and lesion conspicuity (P<0.05) compared to the CE-T2W FSE sequence. CONCLUSION: The PSIL can be an accurate tool for characterizing benign and malignant lesions. The addition of a CE-T2*W GRE sequence is helpful for the detection and characterization of malignant lesions. PMID- 17335041 TI - Forebrain connectivity of the prefrontal cortex in the marmoset monkey (Callithrix jacchus): an anterograde and retrograde tract-tracing study. AB - The cortical and subcortical forebrain connections of the marmoset prefrontal cortex (PFC) were examined by injecting the retrograde tracer, choleratoxin, and the anterograde tracer, biotin dextran amine, into four sites within the PFC. Two of the sites, the lateral and orbital regions, had previously been shown to provide functionally dissociable contributions to distinct forms of behavioral flexibility, attentional set-shifting and discrimination reversal learning, respectively. The dysgranular and agranular regions lying on the orbital and medial surfaces of the frontal lobes were most closely connected with limbic structures including cingulate cortex, amygdala, parahippocampal cortex, subiculum, hippocampus, hypothalamus, medial caudate nucleus, and nucleus accumbens as well as the magnocellular division of the mediodorsal nucleus of the thalamus and midline thalamic nuclei, consistent with findings in the rhesus monkey. In contrast, the granular region on the dorsal surface closely resembled area 8Ad in macaques and had connections restricted to posterior parietal cortex primarily associated with visuospatial functions. However, it also had connections with limbic cortex, including retrosplenial and caudal cingulate cortex as well as auditory processing regions in the superior temporal cortex. The granular region on the lateral convexity had the most extensive connections. Based on its architectonics and functionality, it resembled areas 12/45 in macaques. It had connections with high-order visual processing regions in the inferotemporal cortex and posterior parietal cortex, higher-order auditory and polymodal processing regions in the superior temporal cortex. In addition it had extensive connections with limbic regions including the amygdala, parahippocampal cortex, cingulate, and retrosplenial cortex. PMID- 17335042 TI - Gamma-aminobutyric acid-containing sympathetic preganglionic neurons in rat thoracic spinal cord send their axons to the superior cervical ganglion. AB - Gamma-aminobutyric acid (GABA)-containing fibers have been observed in the rat superior cervical ganglion (SCG) and, to a lesser extent, in the stellate ganglion (STG). The aim of present study is to clarify the source of these fibers. No cell body showed mRNAs for glutamic acid decarboxylases (GADs) or immunoreactivity for GAD of 67 kDa (GAD67) in the cervical sympathetic chain. Thus, GABA-containing fibers in the ganglia are suggested to be of extraganglionic origin. GAD67-immunoreactive fibers were found not in the dorsal roots or ganglia, but in the ventral roots, so GABA-containing fibers in the sympathetic ganglia were considered to originate from the spinal cord. Furthermore, almost all GAD67-immunoreactive fibers in the sympathetic ganglia showed immunoreactivity for vesicular acetylcholine transporter, suggesting that GABA was utilized by some cholinergic preganglionic neurons. This was confirmed by the following results. 1) After injection of Sindbis/palGFP virus into the intermediolateral nucleus, some anterogradely labeled fibers in the SCG were immunopositive for GAD67. 2) After injection of fluorogold into the SCG, some retrogradely labeled neurons in the thoracic spinal cord were positive for GAD67 mRNA. 3) When the ventral roots of the eighth cervical to the fourth thoracic segments were cut, almost all GAD67- and GABA-immunoreactive fibers disappeared from the ipsilateral SCG and STG, suggesting that the vast majority of GABA containing fibers in those ganglia were of spinal origin. Thus, the present findings strongly indicate that some sympathetic preganglionic neurons are not only cholinergic but also GABAegic. PMID- 17335043 TI - Connections of diffuse bipolar cells in primate retina are biased against S cones. AB - In mammalian retina, each diffuse bipolar type stratifies in a distinct layer of the inner plexiform layer. Thus, different types of bipolar cells provide output to distinct visual pathways. Here, the question of whether diffuse bipolar cell types differ with respect to their contacts with short wavelength-sensitive (S-) cones was investigated in the retinas of a New World monkey, Callithrix jacchus, and an Old World monkey, Macaca fascicularis. Subpopulations of OFF bipolar cells were labeled with antibodies to the glutamate transporter Glt-1 and ON bipolar cells were labeled with antibodies to the alpha subunit of the Go protein (Goalpha). Two types of diffuse ON bipolar cells, DB4 and DB6, were identified with antibodies to protein kinase Calpha and CD15, respectively. Cone pedicles were labeled either with peanut agglutinin coupled to fluorescein or with antibodies to the ribbon protein, C-terminus binding protein 2. We found that immunoreactivity for Glt-1 (OFF bipolar cells) is reduced at S-cones in comparison to medium/long wavelength-sensitive (M/L-) cones. Immunoreactivity for Goalpha (ON bipolar cells) is comparable at all cone types. Nearly all M/L-cone pedicles contact the diffuse ON bipolar types DB4 and DB6, but only between 60% and 75% of the S-cone pedicles make contact. Furthermore, the number of dendritic tips of DB4 and DB6 cells at S-cone pedicles is lower than that at M/L-cone pedicles. These results suggest that there is a bias in the S-cone connectivity of diffuse bipolar cells. PMID- 17335044 TI - Differential neuronal and glial expression of GluR1 AMPA receptor subunit and the scaffolding proteins SAP97 and 4.1N during rat cerebellar development. AB - In neurons, AMPA glutamate receptors are developmentally regulated and selectively targeted to synaptic sites. Astroglial cells also express AMPA receptors, but their developmental pattern of expression and targeting mechanisms are unknown. In this study we investigated by immunocytochemistry at the light and electron microscopy level the expression of GluR1 and its scaffolding proteins SAP97 (synapse-associated protein) and 4.1N during cerebellar development. In cerebellar cortex the GluR1 AMPA receptor subunit is expressed exclusively in Bergmann glia in the adult rodent. Interestingly, we observed that GluR1 was expressed postsynaptically at the climbing fibers (CF) synapse at early ages during Purkinje cell dendritic growth and before the complete ensheathment of CF/Purkinje cell synapses by Bergmann glia. However, its expression changed from neurons to Bergmann glia once these glial cells had completed their enwrapping process. In contrast, GluR2/3 and GluR4 AMPAR subunits were stably expressed in both Purkinje cells (GluR2/3) and Bergmann glia (GluR4) throughout postnatal development. Our data indicate that GluR1 expression undergoes a developmental switch from neurons to glia and that this appears to correlate with the degree of Purkinje cell dendritic growth and their enwrapping by Bergmann glia. SAP97 and 4.1N were developmentally regulated in the same pattern as GluR1. Therefore, SAP97 and 4.1N may play a role in the transport and insertion of GluR1 at CF/Purkinje cell synapses during early ages and at Bergmann glia plasma membrane in the adult. The parallel fiber (PF)/Purkinje cell synapse contained GluR2/3 but lacked GluR1, SAP97, and 4.1N at the time of PF synaptogenesis. PMID- 17335045 TI - Homogeneity of intrinsic properties of sexually dimorphic vocal motoneurons in male and female zebra finches. AB - Sex differences in behavioral repertoires are often reflected in the underlying electrophysiological and morphological properties of motor neurons. Male zebra finches produce long, spectrally complex, learned songs and short calls, whereas female finches only produce short, innate, and spectrally simple calls. In both sexes, vocalizations are produced by using syringeal muscles controlled by motoneurons within the tracheosyringeal part of the hypoglossal motor nucleus (XIIts). We asked whether the sexually dimorphic vocal repertoire of adult zebra finches is paralleled by structural and functional differences in syringeal motoneurons. By using immunohistochemical and intracellular staining methods, we describe sex differences in the morphology of XIIts and its surrounding neuropil (suprahypoglossal region; SH). Although the overall number of XIIts neurons and the proportions of somata/neuropil were not sexually dimorphic, the volumes of both XIIts and SH were larger in males, in part because male XIIts neurons had larger somata. In contrast, female XIIts motoneurons had a more complex dendritic structure than did male neurons, suggesting that the larger volume of the male XIIts is due in part to increased numbers of afferents. Intracellular recordings in brain slices revealed that the intrinsic electrophysiological properties of female XIIts neurons were similar to published values for male XIIts motoneurons. We also show that female neurons received glycinergic inputs from the brainstem respiratory premotor column, similar to those described in males. These findings indicate that male and female zebra finches produce their disparate vocal repertoires using physiologically similar motoneurons. Thus, sites upstream of the motoneuron pool may be the major determinants of sexually dimorphic vocal behaviors in this species. PMID- 17335046 TI - Altered localization of gene expression in both ectoderm and mesoderm is associated with a murine strain difference in retinoic acid-induced forelimb ectrodactyly. AB - BACKGROUND: Defects in digit number or fusion as a teratogenic response are well documented in humans and intensively studied in various mouse models. Maternal exposure to excess levels of all-trans-retinoic acid (RA) at gestational day 9.5 induces postaxial ectrodactyly (digit loss) in the murine C57BL/6N strain but not in the SWV/Fnn strain. METHODS: Whole-mount in situ hybridization was used to examine the differential expression of limb patterning genes at the transcriptional level between the two mouse strains following the maternal exposure to a teratogenic level of RA. The detection of a gene with altered expression was followed by either the evaluation of other genes that were synexpressed or with an assessment of downstream genes. RESULTS: In the C57BL/6N limb bud following maternal RA administration, gene-specific perturbations were observed within hours of the RA injection in the posterior pre-AER (apical ectodermal ridge) (Fgf8, Dlx3, Bmp4, Sp8, but not Dlx2 or p63), whereas these genes were normally expressed in the SWV/Fnn limb bud. Furthermore, although RA caused comparable reductions of Shh expression between the strains in the 12 h after administration, some Shh downstream genes were differentially expressed (e.g., Gli1, Ptc, and Hoxd13), whereas others were not (e.g., Fgf4, Bmp4, and Gremlin). CONCLUSIONS: It is proposed that altered gene expression in both pre AER and mesoderm is involved in the pathogenesis of postaxial digit loss, and that because the alterations in the pre-AER occur relatively early in the temporal sequence of events, those changes are candidates for an initiating factor in the malformation. PMID- 17335047 TI - Otolith fibers and terminals in chick vestibular nuclei. AB - The distribution of gravity-sensing, otolith afferent fibers and terminals was studied in the vestibular nuclei of 4-5-day hatchling chicks by using single and double labeling of fibers and terminals with biocytin conjugated to Alexa Fluor and confocal imaging. The vestibular nuclei are represented in a series of five transverse sections of the brainstem immunolabeled with MAP2. Saccular fibers entered the medulla posterior to and at the level of the posterior tangential vestibular nucleus and coursed through ventral parts, producing ascending and descending branches. Small saccular terminals contacted a few dendrites in the tangential nucleus. In contrast, small saccular terminals contacted many dendrites and a few neuron cell bodies in the ventrolateral vestibular nucleus, vestibulocerebellar nucleus, and descending vestibular nuclei. Utricular fibers coursed through ventral parts of the central tangential nucleus before bifurcating into ascending and descending branches. In the tangential nucleus, utricular fibers formed a few large axosomatic terminals (spoon terminals) and a few small terminals on dendrites. In addition, small utricular terminals contacted numerous dendrites and a few neuron cell bodies in the ventrolateral, vestibulocerebellar, and descending vestibular nuclei. Thus, there was negligible overlap in the distribution of the otolith nerves, although each otolith afferent shared common regions with the canal afferents, previously shown, suggesting that some second-order vestibular neurons process convergent inputs from otolith and canal afferents. Taken together with previous results, the present findings identify discrete regions of the chick vestibular nuclei where second-order vestibular neurons likely process directly convergent otolith and canal inputs. PMID- 17335048 TI - Combining visual information from the two eyes: the relationship between isthmotectal cells that project to ipsilateral and to contralateral optic tectum using fluorescent retrograde labels in the frog, Rana pipiens. AB - The frog nucleus isthmi (homolog of the mammalian parabigeminal nucleus) is a visually responsive tegmental structure that is reciprocally connected with the ipsilateral optic tectum; cells in nucleus isthmi also project to the contralateral optic tectum. We investigated the location of the isthmotectal cells that project ipsilaterally and contralaterally using three retrograde fluorescent label solutions: Alexa Fluor 488 10,000 mw dextran conjugate; Rhodamine B isothiocyanate; and Nuclear Yellow. Dye solutions were pressure injected into separate sites in the superficial optic tectum. Following a 6-day survival, brains were fixed, sectioned, and then photographed. Injection of the different labels at separate, discrete locations in the optic tectum result in retrograde filling of singly labeled clusters of cells in both the ipsilateral and contralateral nucleus isthmi. Generally, ipsilaterally projecting cells are dorsal to the contralaterally projecting cells, but there is a slight overlap between the two sets of cells. Nonetheless, when different retrograde labels are injected into opposite tecta, there is no indication that individual cells project to both tecta. The set of cells that project to the ipsilateral tectum and the set of cells that project to the contralateral tectum form a visuotopic map in a roughly vertical, transverse slab. Our results suggest that nucleus isthmi can be separated into two regions with cells in the dorsolateral portion projecting primarily to the ipsilateral optic tectum and cells in the ventrolateral nucleus isthmi projecting primarily to the contralateral optic tectum. PMID- 17335049 TI - Aortic and ventricular dilation and myocardial reduction in gestation day 17 ICR mouse fetuses of diabetic mothers. AB - BACKGROUND: Maternal diabetes mellitus is associated with increased fetal teratogenesis, including cardiovascular defects. Information regarding cardiovascular changes in late-gestation fetal mice, related to maternal hyperglycemia, is not present in the literature. METHODS: Late-gestation fetal heart and great vessel morphology were analyzed in fetuses from control and diabetic mice. Female ICR mice were injected with streptozocin (200 mg/kg IP) prior to mating to induce diabetes (n = 8). Nonhyperglycemic females were used as controls (n = 8). At day 17 of gestation, females were euthanized and one fetus was arbitrarily selected per litter to analyze the heart and great vessels. Six additional fetuses from different litters, showing external malformations (spina bifida and/or exencephaly), were also evaluated from the diabetic group. Fetal thoraxes were processed using routine histopathologic techniques, and 7-mum transversal sections were stained with hematoxylin-eosin. Digital images of sections were made and analyzed using NIH Image J software to compare regional cardiac development. Student's t tests for means were performed to determine differences between groups (p < .05). RESULTS: Maternal hyperglycemia caused a dilation of late-gestation fetal ventricular chambers, a reduction of total ventricular myocardial area, and an increase in transversal ascending thoracic aortic area. Three of six fetuses that displayed external malformations showed an overt cardiac defect, beyond the ventricular and myocardial changes. CONCLUSIONS: Maternal hyperglycemia altered morphology of the late-gestation fetal mouse heart. Postnatal persistence or consequences of late-gestation heart chamber dilation and myocardial reduction are not yet known. PMID- 17335050 TI - Organization of the sensory input to the telencephalon in the fire-bellied toad, Bombina orientalis. AB - The functional organization of sensory activity in the amphibian telencephalon is poorly understood. We used an in vitro brain preparation to compare the anatomy of afferent pathways with the localization of electrically evoked sensory potentials and single neuron intracellular responses in the telencephalon of the toad Bombina orientalis. Anatomical tracing showed that the anterior thalamic nucleus innervates the anterior parts of the medial, dorsal, and lateral pallia and the rostralmost part of the pallium in addition to the subpallial amygdala/ventral pallidum region. Additional afferents to the medial telencephalon originate from the thalamic eminence. Electrical stimulation of diverse sensory nerves and brain regions generated evoked potentials with distinct characteristics in the pallium, subpallial amygdala/ventral pallidum, and dorsal striatopallidum. In the pallium, this sensory activity is generated in the anterior medial region. In the case of olfaction, evoked potentials were recorded at all sites, but displayed different characteristics across telencephalic regions. Stimulation of the anterior dorsal thalamus generated a pattern of activity comparable to olfactory evoked potentials, but it became similar to stimulation of the optic nerve or brainstem after bilateral lesion of the lateral olfactory tract, which interrupted the antidromic activation of the olfactohabenular tract. Intracellular bimodal sensory responses were obtained in the anterior pallium, medial amygdala, ventral pallidum, and dorsal striatopallidum. Our results demonstrate that the amphibian anterior pallium, medial amygdala/ventral pallidum, and dorsal striatopallidum are multimodal sensory centers. The organization of the amphibian telencephalon displays striking similarities with the brain pathways recently implicated in mammalian goal-directed behavior. PMID- 17335051 TI - First vaginal delivery at an older age: Does it carry an extra risk for the development of stress urinary incontinence? AB - AIMS: First delivery at an older age is not an uncommon event in modern obstetric practice. The present study was undertaken to compare the prevalence of postpartum stress urinary incontinence (SUI) according to maternal age and mode of delivery. METHODS: Fifty two consecutive elderly primiparae (mean age 40.0 +/- 1.8) who underwent spontaneous vaginal delivery, 42 consecutive elderly primiparae (mean age 40.7 +/- 3.6) who underwent elective cesarean section, and 92 consecutive young primiparae (mean age 26.2 +/- 2.5) who underwent spontaneous vaginal delivery were interviewed 1-2 years postpartum about the symptom of SUI. Women who had SUI before pregnancy were not enrolled. Obstetric data were collected from computerized hospital records. RESULTS: The prevalence of SUI 1-2 years after spontaneous vaginal delivery was significantly higher in elderly compared with younger primiparae (38.5% vs. 9.8%, respectively). Elderly primiparae who underwent elective cesarean section had a significantly lower prevalence of postpartum SUI than those delivered vaginally (16.7% vs. 38.5%, respectively). Further comparison of stress-incontinent versus continent elderly primiparae failed to reveal significant demographic or obstetric differences, except for increased prevalence of SUI during pregnancy among incontinent patients (45% vs. 19%, respectively). CONCLUSIONS: First vaginal delivery at an older age carries an increased risk for postpartum SUI. Stress-incontinent women also had higher prevalence of SUI during pregnancy. This finding implies that the pathophysiologic process of SUI begins during pregnancy, prior to active labor and delivery. Nonetheless, elective cesarean section in these women has a protective effect and lowers the risk of developing postpartum SUI. PMID- 17335052 TI - Neurophysiologic studies of the penilo-cavernosus reflex: normative data. AB - AIMS: To determine normative values for the penilo-cavernosus reflex on single and double pulse electrical, and mechanical stimulation. METHODS: All men without neurologic disorder, with normal neurologic examination, and with bilaterally normal quantitative electromyography of the external anal sphincter muscles referred for sacral neurophysiologic studies in the years 2003-2005 were included. The penilo-cavernosus reflex was studied on single and double electrical, and mechanical stimulation. Responses were detected by a needle electrode inserted consecutively into the left and right bulbocavernosus muscle. In each subject, latency of the response, and using electrical stimulation, the sensory threshold, reflex threshold and stimulation strength, were determined. Normative values were calculated using parametric statistics and optimal data transformations. RESULTS: In all 26 men with minor non-neurogenic sacral dysfunction reflex responses were recorded using each stimulation technique. Minimal latencies of reflex responses (in msec) were 29.88 +/- 5.65 (upper limit: 39.4), 30.00 +/- 4.11 (36.0), 28.16 +/- 5.80 (35.5) on single electrical, double electrical and mechanical stimulation, respectively. Sensory thresholds (in mA) were 7.80 +/- 2.73 (upper limit: 14.5) and 6.08 +/- 2.30 (10.5), and reflex thresholds (in mA) 25.36 +/- 11.04 (upper limit: 49.6) and 12.78 +/- 6.06 (26.9) on single and double electrical stimulation, respectively. CONCLUSIONS: The obtained normative values for latency on single electrical and mechanical stimulation were similar to those previously published. Additional data on latency on double electrical stimulation, and on the sensory and reflex thresholds on single and double electrical stimulation are expected to increase the diagnostic utility of the penilo-cavernosus reflex. PMID- 17335053 TI - Influence of self-perceived incontinence severity on quality of life and sexual function in women with urinary incontinence. AB - AIMS: We examined the impact of patient-perceived incontinence severity (PPIS) on health-related quality of life (QoL) and sexual function in women with urinary incontinence (UI). METHODS: Patients were recruited from clinic practices at one hospital. Between May 2004 and June 2006, 353 women 27-79 years old (mean 55.7) underwent detailed evaluations. To obtain health-related QoL and sexual function assessments, the patients were asked to fill the questionnaires including the incontinence quality of life (I-QoL) and female sexual function index (FSFI). Patients were categorized into the three groups according to the PPIS; 'mild,' 'moderate,' and 'severe.' RESULTS: Among groups, the duration of symptoms, rate of mixed UI, mean number of treatment visits over the past year, rate of UI associated without any activity, and Valsalva leak point pressure (VLPP) was significantly different (P < 0.05). The I-QoL total score and subscale scores deteriorated significantly as the PPIS increased (P < 0.001). Of the six domains in the FSFI questionnaire, four domains, namely, 'arousal' (P = 0.026), 'lubrication' (P = 0.012), 'orgasm' (P = 0.017), and 'pain' (P = 0.037) as well as the FSFI total score (P = 0.004) were significantly different among the groups. CONCLUSIONS: Our findings suggest that PPIS significantly influences health-related QoL and sexual function, and that strategies for assessing PPIS should be incorporated for assessing patients with UI. PMID- 17335054 TI - Bladder diary patterns in detrusor overactivity and urodynamic stress incontinence. AB - AIMS: Our aims were: (1) to describe and compare frequency-volume and incontinence episode patterns in patients with urodynamic stress incontinence (USI) and detrusor overactivity (DO) as measured by a hand-written and computer analyzed bladder diary and (2) to compare degree of separation between these clinical groups produced by raw diary measurements and after age- and total volume-adjustment against a reference population. MATERIALS AND METHODS: We studied 58 patients with USI, 29 with DO, and 22 with both USI and DO. From 3-day hand-written and computer-analyzed bladder diaries, we calculated average and maximum volume voided (Vol/Void), voiding frequency and volume voided over 24 hr, and number, size and type (whether accompanied by activity or urge) of incontinence episodes. RESULTS: Compared to the USI patients, the DO patients tended to have (1) higher voiding frequency, (2) lower Vol/Void, (3) more urge related, than activity-related leaks, (4) smaller volume, and equally frequent leaks and (5) more severe incontinence symptoms. The age- and volume-adjusted percentiles better separated the USI and DO groups' frequency and volume measurements than did the raw measurements. Unexpectedly high percentages of our USI patients had low Vol/Void measurements, high voiding frequency, and predominantly urge-related leaks. A subgroup of 29 USI patients with "low" (average volume <30th reference population percentile) Vol/Void measurements had high incidences of urgency and urge-related leaks. CONCLUSIONS: Reference population percentiles better separate the frequency/volume patterns of USI and DO than do the raw measurements. We found a subgroup of USI patients that had an OAB-like clinical picture. PMID- 17335055 TI - Normative bladder diary measurements: night versus day. AB - AIMS: To investigate bladder diary measurements from asymptomatic subjects in separate night and day periods, including their relationships to age and total volume voided. A major objective of this study was to generate age-adjusted reference values against which clinical measurements of nocturia can be compared. MATERIALS AND METHODS: Three-day bladder diaries were collected from 161 females and 92 males (age: median=46.5 years; range=19.6-84.6 years). We studied: average volume voided ("Vavg"), voiding frequency, and four urine production measures (volume, production rate, and their ratios to 24-hr values) RESULTS: Both day and night Vavg and frequency increase with increasing volume. The night increase is much steeper than the day increase. With aging, frequency increases, Vavg decreases, day production decreases and night production increases. These age effects are steeper for males than females. Adjusting for age by regression analysis reduces the night production measure's variability by about 40%, and expressing production rate as a percent of the 24-hr value reduces the variability by an additional 20%. CONCLUSIONS: We present regression equations that can be used to adjust night and day Vavg frequency and production rate reference values for the influences of age and total volume. Using these equations, we calculated a table of 95% confidence limits of night urine production and night frequency. The least variable night urine volume measurement studied was night/24-hr production rate; hence this may prove to be the most efficacious measurement to use in detecting nocturnal polyuria. PMID- 17335056 TI - Health care expenditures of children and adults with spina bifida in a privately insured U.S. population. AB - BACKGROUND: We provide new estimates of medical care utilization and expenditures over the lifespan for persons living with spina bifida in the United States. Updated estimates are essential for calculations of lifetime costs and for economic evaluations of prevention and management strategies for spina bifida. METHODS: We analyzed data from the 2001-2003 MarketScan database on paid medical and prescription drug claims of persons covered by employer-sponsored health insurance in the United States. Medical care utilization and expenditures during 2003 were analyzed for persons with a diagnosis of spina bifida recorded during 2001-2003 who had 12 months of coverage in a fee-for-service health plan. To calculate expenditures during infancy, a separate analysis was performed for those born during 2002 with claims and expenditures data during the first 12 months of life. We compared medical expenditures for persons with and without spina bifida by age groups. RESULTS: Average incremental medical expenditures comparing patients with spina bifida and those without were $41,460 per year at age 0, $14,070 at ages 1-17, $13,339 at ages 18-44, and $10,134 at ages 45-64. Children ages 1-17 years with spina bifida had average medical expenditures 13 times greater than children without spina bifida. Adults with spina bifida had average medical expenditures three to six times greater than adults without spina bifida in this privately insured population. CONCLUSIONS: Although per capita medical care utilization and expenditures are highest among children, adults constitute an important and growing share of the population living with spina bifida. PMID- 17335057 TI - Association of zoonotic Ljungan virus with intrauterine fetal deaths. AB - BACKGROUND: It has recently been shown that Ljungan virus (LV) is associated with disease in its wild rodent reservoir. In addition, it has been demonstrated that LV causes malformations and perinatal death in a mouse model. The question was therefore raised whether LV is a zoonotic agent in humans. METHODS: Population fluctuations of native rodents in Sweden were compared to the incidence of intrauterine fetal deaths (IUFDs) using the Swedish national hospitalization database. Formalin-fixed tissues from cases of IUFD were investigated using LV specific immunohistochemistry. RESULTS: Variation in the incidence of IUFDs closely tracked the fluctuations in native rodent populations. LV was detected in the brain tissue in 4 of 10 cases of IUFDs investigated by immunochemistry. LV was also detected in the placenta in 5 of the 10 IUFD cases, but in none of 20 placentas from normal pregnancies. CONCLUSIONS: LV may play an important role in IUFDs. PMID- 17335058 TI - Specific volume and adiabatic compressibility measurements of native and aggregated recombinant human interleukin-1 receptor antagonist: density differences enable pressure-modulated refolding. AB - High hydrostatic pressures have been used to dissociate non-native protein aggregates and foster refolding to the native conformation. In this study, partial specific volume and adiabatic compressibility measurements were used to examine the volumetric contributions to pressure-modulated refolding. The thermodynamics of pressure-modulated refolding from non-native aggregates of recombinant human interleukin-1 receptor antagonist (IL-1ra) were determined by partial specific volume and adiabatic compressibility measurements. Aggregates of IL-1ra formed at elevated temperatures (55 degrees C) were found to be less dense than native IL-1ra and refolded at 31 degrees C under 1,500 bar pressure with a yield of 57%. Partial specific adiabatic compressibility measurements suggest that the formation of solvent-free cavities within the interior of IL-1ra aggregates cause the apparent increase in specific volume. Dense, pressure-stable aggregates could be formed at 2,000 bar which could not be refolded with additional high pressure treatment, demonstrating that aggregate formation conditions and structure dictate pressure-modulated refolding yields. PMID- 17335059 TI - Development of an automated SNP analysis method using a paramagnetic beads handling robot. AB - Biological and medical importance of the single nucleotide polymorphism (SNP) has led to development of a wide variety of methods for SNP typing. Aiming for establishing highly reliable and fully automated SNP typing, we have developed the adapter ligation method in combination with the paramagnetic beads handling technology, Magtration(R). The method utilizes sequence specific ligation between the fluorescently labeled adapter and the sample DNAs at the cohesive end produced by a type IIS restriction enzyme. Evaluation of the method using human genomic DNA showed clear discrimination of the three genotypes without ambiguity using the same reaction condition for any SNPs examined. The operations following PCR amplification were automatically performed by the Magtration(R)-based robot that we have previously developed. Multiplex typing of two SNPs in a single reaction by using four fluorescent dyes was successfully preformed at the almost same sensitivity and reliability as the single typing. These results demonstrate that the automated paramagnetic beads handling technology, Magtration(R), is highly adaptable to the automated SNP analysis and that our method best fits to an automated in-house SNP typing for laboratory and medical uses. PMID- 17335060 TI - Steric and electrostatic interactions govern nanofiltration of amino acids. AB - Crossflow nanofiltration experiments were performed to investigate the factors influencing the removal of amino acids by a commercially available polymeric thin film composite membrane. The removals of five monoprotic (Ala, Val, Leu, Gly, and Thr), one diprotic (Asp), and one dibasic (Arg) amino acids in a range of permeate fluxes, feed pH values, and ionic strengths were analyzed using a phenomenological model of membrane transport. At any given pH and ionic strength, reflection coefficients (rejection at asymptotically infinite flux) of monoprotic amino acids increased with molar radius demonstrating the role of steric interactions on their removal. Additionally, consistent with Donnan exclusion, higher reflection coefficients were obtained when the membrane and the amino acids both carried the same nature of charge (positive or negative). In other words, both co-ion repulsion and molecular size determined amino acids removal. Importantly, the removal of effectively neutral amino acids were significantly higher than neutral sugars and alcohols of similar size demonstrating that even near their isoelectric point, zwitterionic characteristics preclude them from being considered as strictly neutral. PMID- 17335061 TI - Physiological characterization of xylose metabolism in Aspergillus niger under oxygen-limited conditions. AB - The physiology of Aspergillus niger was studied under different aeration conditions. Five different aeration rates were investigated in batch cultivations of A. niger grown on xylose. Biomass, intra- and extra-cellular metabolites profiles were determined and ten different enzyme activities in the central carbon metabolism were assessed. The focus was on organic acid production with a special interest in succinate production. The fermentations revealed that oxygen limitation significantly changes the physiology of the micro-organism. Changes in extra cellular metabolite profiles were observed, that is, there was a drastic increase in polyol production (erythritol, xylitol, glycerol, arabitol, and mannitol) and to a lesser extent in the production of reduced acids (malate and succinate). The intracellular metabolite profiles indicated changes in fluxes, since several primary metabolites, like the intermediates of the TCA cycle accumulated during oxygen limitation (on average three fold increase). Also the enzyme activities showed changes between the exponential growth phase and the oxygen limitation phase. In general, the oxygen availability has a significant impact on the physiology of this fungus causing dramatic alterations in the central carbon metabolism that should be taken into account in the design of A. niger as a succinate cell factory. PMID- 17335062 TI - High-throughput screening of packed-bed chromatography coupled with SELDI-TOF MS analysis: monoclonal antibodies versus host cell protein. AB - A feasibility study to couple high throughput screening of packed bed chromatography with mass spectrometric detection by SELDI-TOF MS is presented. As model system monoclonal antibodies (mAb) versus host cell protein (HCP) from an industrial cultivation was chosen. Packed bed chromatography was screened on a TECAN Evo Freedom 200 station using miniaturized chromatographic columns placed on a specially designed array carrier linked to a commercially available T-Stack module. Gradient elution of the bound proteins was performed by applying a multiple step strategy. When analyzing selected HCP peaks as well as the detected antibody peaks throughout the chromatographic runs a direct correlation between applied and detected components was established. The sensitivity of conventional protein A chromatography was found to be lower than SELDI-TOF MS analysis. During initial screening a shift in the elution pattern for one of the monoclonal antibodies detected with all four resins was identified to be a heterogeneity in the mAb glycosylation pattern. In addition, a detailed differentiation between various HCP fractions through out the chromatographic process using SELDI-TOF analysis let to the detection of HCP components possibly adhering to the mAbs during chromatographic separations. PMID- 17335063 TI - Quantification of magnetic susceptibility in several strains of Bacillus spores: implications for separation and detection. AB - Three strains of Bacillus: Bacillus atrophaeus (formally Bacillus globigii), Bacillus thuringiensis, and Bacillus cereus were tested for their intrinsic magnetic susceptibility. All three strains when sporulated demonstrated significant magnetic susceptibility using an instrument referred to as Cell Tracking Velocimetry. Energy dispersive spectroscopy also confirmed the presence of paramagnetic elements, Fe and Mn, in the spore form of the bacteria. It was demonstrated that this magnetic susceptibility is sufficient to separate and deposit these spores on glass slides in a magnetic deposition system. These results indicate the potential to separate spores with intrinsic magnetic susceptibility directly out of water or air samples. PMID- 17335064 TI - Cellulase digestibility of pretreated biomass is limited by cellulose accessibility. AB - Attempts to correlate the physical and chemical properties of biomass to its susceptibility to enzyme digestion are often inconclusive or contradictory depending on variables such as the type of substrate, the pretreatment conditions and measurement techniques. In this study, we present a direct method for measuring the key factors governing cellulose digestibility in a biomass sample by directly probing cellulase binding and activity using a purified cellobiohydrolase (Cel7A) from Trichoderma reesei. Fluorescence-labeled T. reesei Cel7A was used to assay pretreated corn stover samples and pure cellulosic substrates to identify barriers to accessibility by this important component of cellulase preparations. The results showed cellulose conversion improved when T. reesei Cel7A bound in higher concentrations, indicating that the enzyme had greater access to the substrate. Factors such as the pretreatment severity, drying after pretreatment, and cellulose crystallinity were found to directly impact enzyme accessibility. This study provides direct evidence to support the notion that the best pretreatment schemes for rendering biomass more digestible to cellobiohydrolase enzymes are those that improve access to the cellulose in biomass cell walls, as well as those able to reduce the crystallinity of cell wall cellulose. PMID- 17335065 TI - Microscopic analysis of corn fiber using starch- and cellulose-specific molecular probes. AB - Ethanol is the primary liquid transportation fuel produced from renewable feedstocks in the United States today. The majority of corn grain, the primary feedstock for ethanol production, has been historically processed in wet mills yielding products such as gluten feed, gluten meal, starch, and germ. Starch extracted from the grain is used to produce ethanol in saccharification and fermentation steps; however the extraction of starch is not 100% efficient. To better understand starch extraction during the wet milling process, we have developed fluorescent probes that can be used to visually localize starch and cellulose in samples using confocal microscopy. These probes are based on the binding specificities of two types of carbohydrate binding modules (CBMs), which are small substrate-specific protein domains derived from carbohydrate degrading enzymes. CBMs were fused, using molecular cloning techniques, to a green fluorescent protein (GFP) or to the red fluorescent protein DsRed (RFP). Using these engineered probes, we found that the binding of the starch-specific probe correlates with starch content in corn fiber samples. We also demonstrate that there is starch internally localized in the endosperm that may contribute to the high starch content in corn fiber. We also surprisingly found that the cellulose specific probe did not bind to most corn fiber samples, but only to corn fiber that had been hydrolyzed using a thermochemical process that removes the residual starch and much of the hemicellulose. Our findings should be of interest to those working to increase the efficiency of the corn grain to ethanol process. PMID- 17335066 TI - Continuous fermentation of wheat-supplemented lignocellulose hydrolysate with different types of cell retention. AB - Medium supplementation and process alternatives for fuel ethanol production from dilute acid lignocellulose hydrolysate were investigated. Dilute acid lignocellulose hydrolysate supplemented with enzymatically hydrolysed wheat flour could sustain continuous anaerobic cultivation of Saccharomyces cerevisiae ATCC 96581 if further supplemented with ammonium sulphate and biotin. This medium composition allowed for a hexose utilisation of 73% and an ethanol production of 36 mmol l(-1) h(-1) in chemostat cultivation at dilution rate 0.10 h(-1). Three different methods for cell retention were compared for improved fermentation of supplemented lignocellulose hydrolysate: cell recirculation by filtration, cell recirculation by sedimentation and cell immobilisation in calcium alginate. All three cell retention methods improved the hexose conversion and increased the volumetric ethanol production rate. Recirculation of 75% of the bioreactor outlet flow by filtration improved the hexose utilisation from 76% to 94%. Sedimentation turned out to be an efficient method for cell separation; the cell concentration in the reactor was 32 times higher than in the outflow after 60 h of substrate feeding. However, chemostat and continuous cell recirculation cultures became severely inhibited when the dilution rate was increased to 0.20 h(-1). In contrast, an immobilised system kept producing ethanol at a stable level also at dilution rate 0.30 h(-1). PMID- 17335067 TI - Correction of proton resonance frequency shift temperature maps for magnetic field disturbances using fat signal. AB - PURPOSE: To improve the immunity of the proton resonance frequency shift (PRFS) method of MRI temperature mapping against magnetic field disturbances. Since PRFS is a phase-sensitive method, it misinterprets magnetic field disturbances as artifact temperature changes. If not corrected, the resulting temperature artifacts can completely obscure the true temperature estimation, especially if the temperature elevations are small. MATERIALS AND METHODS: Since the fat protons experience the same magnetic field disturbances as the water protons, but no temperature-related frequency shift, the fat signal has been used for correcting PRFS temperature maps for the disturbances. A simple correction method is proposed that has either better compensation capability than the phase correction methods previously reported or higher spatial and temporal resolution than the spectroscopic correction methods previously reported. The evaluated method is based on the utilization of several gradient and spin echoes acquired within one repetition interval with water- and fat-selective scans. RESULTS: In a series of phantom experiments, the improved method is shown to enable the reconstruction of accurate temperature maps in spite of interscan motion, suboptimal fat-water separation, and a wide range of magnetic field disturbances. CONCLUSION: Our approach can be used for the guidance of thermal therapies involving tissues containing fat or surrounded by fat. PMID- 17335070 TI - Palladium-based catalytic systems for the synthesis of conjugated enynes by sonogashira reactions and related alkynylations. AB - Conjugated alkynes are recurring building blocks in natural products, a wide range of industrial intermediates, pharmaceuticals and agrochemicals, and molecular materials for optics and electronics. The palladium-catalyzed cross coupling between sp(2)-hybridized carbon atoms of aryl, heteroaryl, and vinyl halides with sp-hybridized carbon atoms of terminal acetylenes is one of the most important developments in the field of alkyne chemistry over the past 50 years. The seminal work of the 1970s has initiated an intense search for more general and reliable reaction conditions. The interest in the catalytic activation of demanding substrates, the need to minimize the consumption of depletive resources, and the search for easy access to an increased variety of functionalized enynes has led to the current generations of high-turnover catalysts. This Review gives an overview of the highly efficient palladium catalyst systems for the direct alkynylation of C(sp(2)) halides with terminal alkynes, both in homogeneous and heterogeneous phases. PMID- 17335072 TI - Tumor necrosis factor-alpha up-regulates glucuronosyltransferase gene expression in human brain endothelial cells and promotes T-cell adhesion. AB - Stimulation of human brain microvascular endothelial cells (SV-HCECs) with tumor necrosis factor-alpha (TNF-alpha) up-regulates sulfoglucuronosyl paragloboside (SGPG) synthesis in a dose- and time-dependent manner. After TNF-alpha exposure at a concentration of 50 ng/ml for 24 hr, we observed a seven- to tenfold elevation of SGPG concentration. Interleukin-1beta (IL-1beta) at a concentration of 10 ng/ml and the combined doses of TNF-alpha and IL-1beta were less effective than TNF-alpha alone. TNF-alpha also stimulated T-cell (Jurkat) adhesion with SV HCECs via SGPG-L-selectin recognition: this was determined by double-label immunofluorescent staining with SGPG and L-selectin antibodies. The number of T cells bound to SV-HCECs after different cytokine stimulations was proportional to the SGPG concentration, and the cell attachment was inhibited by anti-SGPG and anti-L-selectin antibodies, respectively. Our data unequivocally establish that inflammatory cytokines, particularly TNF-alpha, stimulate the glucuronosyltransferse, GlcAT-P, and GlcAT-S, gene expression in brain endothelial cells and promote T-cell adhesion via SGPG-L-selectin recognition, a preliminary step for onset of neuroinflammation. PMID- 17335073 TI - Plexiform-like neurofibromas develop in the mouse by intraneural xenograft of an NF1 tumor-derived Schwann cell line. AB - Plexiform neurofibromas are peripheral nerve sheath tumors that arise frequently in neurofibromatosis type 1 (NF1) and have a risk of malignant progression. Past efforts to establish xenograft models for neurofibroma involved the implantation of tumor fragments or heterogeneous primary cultures, which rarely achieved significant tumor growth. We report a practical and reproducible animal model of plexiform-like neurofibroma by xenograft of an immortal human NF1 tumor-derived Schwann cell line into the peripheral nerve of scid mice. The S100 and p75 positive sNF94.3 cell line was shown to possess a normal karyotype and have apparent full-length neurofibromin by Western blot. These cells were shown to have a constitutional NF1 microdeletion and elevated Ras-GTP activity, however, suggesting loss of normal neurofibromin function. Localized intraneural injection of the cell line sNF94.3 produced consistent and slow growing tumors that infiltrated and disrupted the host nerve. The xenograft tumors resembled plexiform neurofibromas with a low rate of proliferation, abundant extracellular matrix (hypocellularity), basal laminae, high vascularity, and mast cell infiltration. The histologic features of the developed tumors were particularly consistent with those of human plexiform neurofibroma as well. Intraneural xenograft of sNF94.3 cells enables the precise initiation of intraneural, plexiform-like tumors and provides a highly reproducible model for the study of plexiform neurofibroma tumorigenesis. This model facilitates testing of potential therapeutic interventions, including angiogenesis inhibitors, in a relevant cellular environment. PMID- 17335074 TI - Anterograde axonal transport of chicken cellular prion protein (PrPc) in vivo requires its N-terminal part. AB - The cellular isoform of prion protein (PrP(c)) can exist in membrane-bound and secreted forms. Both forms of PrP(c) can be transported by retinal ganglion cell (RGC) axons along the optic nerve in the anterograde direction. In this study we determined which part of chicken PrP(c) is required for its anterograde axonal transport within the optic nerve of embryonic chicken. We intraocularly injected radio-iodinated fragments of recombinant chicken PrP(c) and then examined their anterograde axonal transport from retina into optic tectum. Using gamma-counting and different autoradiographic techniques we quantified anterograde axonal transport of the N-terminal part of chicken PrP(c) (amino acid residues 1-116) in this model system. The transport of the N-terminal part has similar properties as the anterograde transport of full-length chicken PrP(c) (Butowt et al., 2006) described previously (e.g., has similar efficiency, is microtubule-dependent, and is saturable). Moreover, the pattern of ultrastructural distribution of the N terminal fragment within RGCs is similar to the distribution of full-length PrP(c). The C-terminal fragment of chicken PrP(c) (residues 118-246) and different PrP-derived peptides were not transported. Moreover, PrP(c)-derived peptides were sorted into different endocytotic pathways in neurons, indicating that they cannot substitute for full-length PrP(c) to study its internalization and trafficking. These data indicate that the N-terminal half of chicken PrP(c) contains the necessary information to drive the internalization and subsequent sorting of extracellular PrP(c) in RGCs soma into the anterograde axonal transport pathway. PMID- 17335075 TI - beta-amyloid precursor protein can be transported independent of any sorting signal to the axonal and dendritic compartment. AB - In neurons, amyloid precursor protein (APP) is localized to the dendritic and axonal compartment. Changes in subcellular localization affect secretase cleavage of APP, altering the generation of Abeta, and presumably also its pathogenic features. It was reported that APP is sorted initially to the axon and transcytosed subsequently to the somatodendritic compartment. This may be carried out by a recessive dendritic sorting signal in the cytoplasmic C-terminus, possibly the tyrosine based basolateral sorting signal (BaSS), and an axonal sorting motif within the extracellular juxtamembraneous domain. We investigated whether the C- or N-terminal domain of APP contains an independent dendritic or axonal sorting signal. We generated different APP deletion mutants, and produced chimeric proteins of APP and a non-related Type I transmembrane protein. Quantitative immunocytochemical analyses of transfected primary neurons showed that similar amounts of all APP mutants, lacking either the N- or C-terminus, were transported to the axonal and dendritic compartment. Investigations of the chimeric proteins showed that neither the N- nor the C-terminus of APP functions as independent sorting signal, whereas another tyrosine based dendritic sorting signal was sufficient to prevent axonal entry of APP. This data shows that, under steady state conditions, Heterologously expressed APP is transported equally to axons and dendrites irrespective of any putative sorting signal in its N- or C terminus. This shows that APP can enter the axon in absence of the initial axonal sorting motif, indicating the existence of an alternative pathway allowing axonal entry of APP. PMID- 17335077 TI - Studies of the central nervous system-derived CAD cell line, a suitable model for intraneuronal transport studies? AB - The CAD cell line is a variant of a CNS-derived Cath.a cell line established by targeted oncogenesis in transgenic mice. Cell differentiation of the cell line can be induced by "starvation," i.e., removal of serum from the culture medium (protein-free medium). The differentiated CAD cells extend long processes, which ultrastructurally contain abundant microtubules, intermediate filaments, and various synaptic vesicles/organelles in the varicose enlargements, thus resembling neurites. Histochemical studies demonstrated that the differentiated cells express a number of synaptic vesicle proteins, cytoskeletons, different neurotransmitter enzymes, neuropeptides, and glia proteins. The data suggest that the differentiated CAD cells may be a suitable model for studies of intraneuronal transport, recycling of receptors, and pharmacological investigations. PMID- 17335076 TI - Induction of transforming growth factor-beta1 by basic fibroblast growth factor in rat C6 glioma cells and astrocytes is mediated by MEK/ERK signaling and AP-1 activation. AB - Basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF beta1) play an important role in proliferation, differentiation, and survival of malignant gliomas and in normal glial cell biology. Because of these critical roles, potential interactions between these key growth factors were investigated. We previously demonstrated that bFGF potently stimulates TGF-beta1 release from rat glioma cells. The purpose of the present study was to elucidate the mechanism(s) of this regulatory effect, establish its functional importance, and examine whether it extends to nontransformed rat hypothalamic astrocytes (RHA). The results revealed that RHA express the high-affinity FGF(1-4) receptors, and similarly to glioma cells, bFGF stimulated TGF-beta1 release in an isoform specific manner. A mediatory role for ERK signaling in bFGF-induced TGF-beta release was suggested by the fact that MEK1 inhibition prevented this effect. Additionally, bFGF enhanced MEK1/2 phosphorylation and ERK activation/nuclear translocation, which culminated in increased activity of AP-1-mediated gene transcription. bFGF markedly induced TGF-beta1 mRNA levels in an isoform-specific manner, an effect that was dependent on MEK/ERK/AP-1 signaling. Functionally, bFGF-induced proliferation of glioma cells was attenuated by MEK/ERK inhibition or immunoneutralization of TGF-beta1, suggesting that this pathway may have important implications for brain tumor progression. PMID- 17335078 TI - Simultaneous age-related depolarization of mitochondrial membrane potential and increased mitochondrial reactive oxygen species production correlate with age related glutamate excitotoxicity in rat hippocampal neurons. AB - Mitochondria are implicated in glutamate excitotoxicity by causing bioenergetic collapse, loss of Ca(2+) homeostasis, and generation of reactive oxygen species (ROS), all of which become increasingly important clinically with age. Little is known about how aging affects the relative importance of mitochondrial membrane potential (DeltaPsi(m)) and ROS production. To determine aging affects on DeltaPsi(m) and ROS production in individual somal and axonal/dendritic mitochondria, we compared ROS production while simultaneously monitoring DeltaPsi(m) before and after glutamate treatment of live neurons from embryonic (day 18), middle-aged (9-12 months), and old (24 months) rats. At rest, old neuronal mitochondria 1) showed a higher rate of ROS production that was particularly strong in axonal/dendritic mitochondria relative to that in middle age neurons, 2) were more depolarized in comparison with neurons of other ages, and 3) showed no differences in ROS or DeltaPsi(m) as a function of distance from the nucleus. All DeltaPsi(m) grouped into three classes of high (less than -120 mV), medium (-85 to -120 mV), and low (greater than -85 mV) polarization that shifted toward the lower classes with age at rest. Glutamate exposure dramatically depolarized the DeltaPsi(m) in parallel with greatly increased ROS production, with a surprising absence of an effect of age or distance from the nucleus on these mitochondrial parameters. These data suggest that old neurons are more susceptible to glutamate excitotoxicity because of an insidious depolarization of DeltaPsi(m) and rate of ROS generation at rest that lead to catastrophic failure of phosphorylative and reductive energy supplies under stress. PMID- 17335079 TI - Embryonic stem cells produce neurotrophins in response to cerebral tissue extract: Cell line-dependent differences. AB - In the present study, we compare the capacity of two different embryonic stem (ES) cell lines to secrete neurotrophins in response to cerebral tissue extract derived from healthy or injured rat brains. The intrinsic capacity of the embryonic cell lines BAC7 (feeder cell-dependent cultivation) to release brain derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) exceeded the release of these factors by CGR8 cells (feeder cell-free growth) by factors of 10 and 4, respectively. Nerve growth factor (NGF) was secreted only by BAC7 cells. Conditioning of cell lines with cerebral tissue extract derived from healthy or fluid percussion-injured rat brains resulted in a significant time-dependent increase in BDNF release in both cell lines. The increase in BDNF release by BAC7 cells was more pronounced when cells were incubated with brain extract derived from injured brain. However, differences in neurotrophin release associated with the origin of brain extract were at no time statistically significant. Neutrophin 3 and NGF release was inhibited when cell lines were exposed to cerebral tissue extract. The magnitude of the response to cerebral tissue extract was dependent on the intrinsic capacity of the cell lines to release neurotrophins. Our results clearly demonstrate significant variations in the intrinsic capability of different stem cell lines to produce neurotrophic factors. Furthermore, a significant modulation of neurotrophic factor release was observed following conditioning of cell lines with tissue extract derived from rat brains. A significant modulation of neurotrophin release dependent on the source of cerebral tissue extract used was not observed. PMID- 17335080 TI - Roles of glial p75NTR in axonal regeneration. AB - The neurotrophin receptor p75 (p75NTR) is expressed by both neurons and glia. Nerve injury triggers up-regulation of p75NTR in Schwann cells (SC) but not in central glia. In contrast to neuronal p75NTR, which mediates negative signals from myelin-associated proteins resulting in neurite collapse, glial p75NTR may play a positive role in nerve regeneration by forming neurotrophin chemoattractant gradients or by competitively antagonizing the NOGO/NgR/LINGO-1 signal through cell-cell contact or regulated intramembranous proteolysis (RIP) of p75NTR. This piece presents some recent evidence supporting this hypothesis. PMID- 17335081 TI - Schwann cells express IP prostanoid receptors coupled to an elevation in intracellular cyclic AMP. AB - We have shown previously that prostaglandin E(2) (PGE(2)) and prostaglandin I(2) (PGI(2)) are each produced in an explant model of peripheral nerve injury. We report that IP prostanoid receptor mRNA and protein are present in primary rat Schwann cells. IP prostanoid receptor stimulation using prostacyclin produced an elevation in intracellular cyclic AMP concentration ([cAMP](i)) in primary Schwann cells. Peak [cAMP](i) was observed between 5-15 min of stimulation followed by a gradual recovery toward basal level. Phosphorylation of cyclic AMP response element binding protein (CREB) on Ser(133) was also detected after IP prostanoid receptor stimulation and CREB phosphorylation was inhibited completely by the protein kinase A inhibitor, H-89. Intracellular calcium levels were not affected by IP prostanoid receptor stimulation. Unlike forskolin, IP prostanoid receptor stimulation did not significantly augment Schwann cell proliferation in response to growth factor treatment. However, IP prostanoid receptor stimulation increased the number of Schwann cells that were able to generate a calcium transient in response to P2 purinergic receptor activation. These findings suggest that signaling via the IP prostanoid receptor may by relevant to Schwann cell biology in vivo. PMID- 17335082 TI - Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood-brain barrier disturbance but not with patient survival. AB - Aquaporin-4 (AQP4), the most prominent CNS water channel, is restricted to the glia limitans and astrocytic endfeet. We previously showed the loss of spatial AQP4 expression in glioblastomas and a redistribution across the cell surface. However, opposing AQP4 functions have been described: protective in vasogenic but detrimental in cytotoxic brain edema. Thus, specific AQP4 induction to prevent or reduce vasogenic edema is suggested. To elucidate the AQP4 role in brain tumors, we investigated 189 WHO grade I-IV gliomas by immunohistochemistry and the prognostic significance for patients' survival. In gliomas, a remarkable de novo AQP4 redistribution was observed in comparison with normal CNS tissue. Surprisingly, the highest membraneous staining levels were seen in pilocytic astrocytomas WHO grade I and grade IV glioblastomas, both significantly higher than in WHO grade II astrocytomas. AQP4 up-regulation was associated with brain edema formation; however, no association between survival and WHO grade-dependent AQP4 expression was seen. Hence, AQP4 redistribution may go along with other tumor properties, such as vascular proliferation and resulting blood-brain barrier disturbance, features usually prominent in pilocytic astrocytomas WHO I and glioblastomas WHO grade IV. In summary, our findings question the protective role of AQP4 in vasogenic brain edema. Although AQP4 was associated with brain edema formation, one has to question the suitability of AQP4 induction as a promising approach in vasogenic brain edema prevention and treatment. In addition, our results provide unexpectedly high AQP4 levels in pilocytic astrocytomas and present AQP4 as tumor progression marker in WHO grade II-IV astrocytomas. PMID- 17335083 TI - Increased levels of fucosyltransferase IX and carbohydrate Lewis(x) adhesion determinant in human NT2N neurons. AB - The expression of the fucosylated carbohydrate Lewis(x) (Le(x)) determinant (Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc-R) has been found in glycoproteins, proteoglycans, and glycolipids from the nervous system. Evidence suggests its association with cell-cell recognition, neurite outgrowth, and neuronal migration during central nervous system development. In the present work, we detected increased levels of Le(x) in differentiated human NT2N neurons cultured in vitro. To identify which fucosyltransferase (FUT) synthesized the Le(x) in NT2N neurons, RT-PCR, FUT substrate specificity and Western blot analysis were carried out. Strong activity toward acceptors Galbeta4GlcNAc-O-R and Fucalpha2Galbeta4GlcNAc-O R [R = -(CH(2))(3)NHCO(CH(2))(5)NH-biotin], together with strong FUT9 detection by Western blot and presence of transcripts showed that FUT9 was the enzyme associated with Le(x) biosynthesis in NT2N neurons. Le(x) was detected at the plasma membrane of NT2N neurons, in lysosomes marked with lysosomal-associated membrane protein 1 (LAMP-1), and it was found for the first time to colocalize with the tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI VAMP) that defines the TI-VAMP exocytic compartment that is involved in neurite outgrowth. Furthermore, incubation with anti-Le(x) monoclonal antibody L5 led to impaired adhesion of NT2N neurons to the surface matrix and inhibited neurite initiation. In conclusion, FUT9 and its product Le(x) are detected specifically in human NT2N neurons and our results indicate that they underlie cell differentiation, cell adhesion, and initiation of neurite outgrowth in those neurons. PMID- 17335084 TI - S/P and T/P phosphorylation is critical for tau neurotoxicity in Drosophila. AB - The microtubule-associated protein tau is hyperphosphorylated abnormally in AD and related neurodegenerative disorders. Many phospho epitopes created by proline directed kinases (SP/TP sites) show relative specificity for disease states. To test whether phosphorylation at the disease-associated SP/TP sites affects tau toxicity in vivo, we expressed a form of tau in Drosophila in which all SP/TP sites are mutated to alanine. We find that blocking phosphorylation at SP/TP motifs markedly reduces tau toxicity in vivo. Using phosphorylation-specific antibodies, we identify a positive correlation between increased phosphorylation at disease-associated sites and neurotoxicity. We use the phosphorylation incompetent version of tau to show that kinase and phosphatase modifiers of tau neurotoxicity, including cdk5/p35, the JNK kinase hemipterous and PP2A act via SP/TP phosphorylation sites. We provide direct evidence in an animal model system to support the role of phosphorylation at SP/TP sites in playing a critical role in tau neurotoxicity. PMID- 17335085 TI - Transplantation of post-mitotic human neuroteratocarcinoma-overexpressing Nurr1 cells provides therapeutic benefits in experimental stroke: in vitro evidence of expedited neuronal differentiation and GDNF secretion. AB - Nurr1 has been implicated as a transcription factor mediating the endogenous neuroprotective mechanism against stroke. We examined the in vivo and in vitro properties of a new human embryonic carcinoma Ntera-2 cell line carrying the human Nurr1 gene (NT2N.Nurr1). Adult Sprague-Dawley rats underwent experimental stroke initially and 14 days later were assigned randomly to receive stereotaxic transplantation of NT2N.Nurr1 cells or infusion of vehicle into their ischemic striatum. Transplantation of NT2N.Nurr1 cells promoted significant attenuation of behavioral impairments over a 56-day period after stroke, characterized by decreased hyperactivity, biased swing activity, and neurologic deficits, as well as significant reduction in ischemic striatal cell loss compared to vehicle infused stroke animals. Transplanted NT2N.Nurr1 cells survived and expressed neuronal phenotypic markers in the ischemic striatum. In vitro results showed that cultured NT2.Nurr1 cells were already negative for nestin even before retinoic acid treatment, despite strong nestin immunoreactivity in NT2 cells. This indicates Nurr1 triggered a rapid commitment of NT2 cells into a neuronal lineage. Indeed, NT2.Nurr1 cells, at 4 weeks into RA treatment, displayed more abundant tyrosine hydroxylase positive cells than NT2 cells. Parallel ELISA studies showed further that cultured NT2N.Nurr1, but not NT2N cells, secreted glial cell derived neurotrophic factor. The present study shows efficacy of NT2N.Nurr1 cell grafts in ischemic stroke, with in vitro evidence suggesting the cells' excellent neuronal differentiation capability and ability to secrete GDNF as likely mechanisms mediating the observed therapeutic benefits. PMID- 17335087 TI - Neuregulins at the neuromuscular synapse: past, present, and future. AB - At the developing vertebrate neuromuscular junction, neuregulins are growth/differentiation factors essential for terminal Schwann cell survival. Neuregulins have also been thought as the critical signals responsible for the increased transcription of acetylcholine receptor subunit genes at the neuromuscular synapse. This latter role is now highly controversial. This article reviews the evidence that has shaped the views of the neuregulins and how these views have been challenged. The most recent experiments indicate that neuregulin signaling to postsynaptic muscle fibers may modulate, rather than determine, acetylcholine receptor expression at the neuromuscular junction. Based on findings from my lab and those of others, I propose that this modulation might involve novel posttranscriptional molecular mechanisms. Finally, I also suggest that neuregulin signaling may have an important role to play in mediating the response of adult terminal Schwann cells to denervation. PMID- 17335086 TI - Neuritin (cpg15) enhances the differentiating effect of NGF on neuronal PC12 cells. AB - Neuritin is a small, highly conserved GPI-anchored protein involved in neurite outgrowth. We have analyzed the involvement of neuritin in NGF-induced differentiation of PC12 cells by investigating the time-course of neuritin expression, the effects of its overexpression or silencing, and the possible mechanisms of its regulation and action. Real-time PCR analysis has shown that neuritin gene is upregulated by NGF in PC12 cells hours before neurite outgrowth becomes appreciable. PC12 cells transfected with a plasmid expressing neuritin display a significant increase in the response to NGF: 1) in the levels of SMI312 positive phosphorylated neurofilament proteins (markers for axonal processes) and tyrosine hydroxylase; 2) in the percentage of cells bearing neurites; as well as 3) in the average length of neurites when compared to control cells. On the contrary, neuritin silencing significantly reduces neurite outgrowth. These data suggest that neuritin is a modulator of NGF-induced neurite extension in PC12 cells. We also showed that neuritin potentiated the NGF-induced differentiation of PC12 cells without affecting TrkA or EGF receptor mRNAs expression. Moreover, the S-methylisothiourea (MIU), a potent inhibitor of inducible nitric oxide synthases, partially counteracts the NGF-mediated neuritin induction. These data suggest that NGF regulates neuritin expression in PC12 cells via the signaling pathway triggered by NO. This study reports the first evidence that neuritin plays a role in modulating neurite outgrowth during the progression of NGF induced differentiation of PC12 cells. PC12 cells could be considered a valuable model to unravel the mechanism of action of neuritin on neurite outgrowth. (c) 2007 Wiley-Liss, Inc. PMID- 17335088 TI - Unilateral hippocampal blockade reveals that one hippocampus is sufficient for learning a passive avoidance task. AB - Understanding hippocampal participation in memory processes is one of the goals in neuroscience research. By blocking the hippocampus unilaterally in Wistar rats, we assessed the contribution of this brain structure to memory in a passive avoidance task. Subjects were distributed into four groups. Group 1 received tetrodotoxin (TTX) in the right hippocampus during acquisition and retrieval phases. Group 2 had the same procedure as group 1, except that the contralateral hippocampus was blocked during retrieval. Subjects from group 3 acquired the task with saline (both hippocampi intact) and retrieved with the right hippocampus inactivated. Finally, group 4 received TTX unilaterally 2 min after acquisition to determine the hippocampal role in consolidation. Results showed that group 2 was impaired, compared with the other groups, during retrieval. These findings reveal that the hippocampal contribution to this task differs from that in other tasks considered to be hippocampus dependent. PMID- 17335089 TI - Mechanisms of oxidation of guanine in DNA by carbonate radical anion, a decomposition product of nitrosoperoxycarbonate. AB - Peroxynitrite is produced during inflammation and combines rapidly with carbon dioxide to yield the unstable nitrosoperoxycarbonate, which decomposes (in part) to CO(3) (.-) and (.)NO(2) radicals. The CO(3) (.-) radicals oxidize guanine bases in DNA through a one-electron transfer reaction process that ultimately results in the formation of stable guanine oxidation products. Here we have explored these mechanisms, starting with a spectroscopic study of the kinetics of electron transfer from 20-22mer double-stranded oligonucleotides to CO(3) (.-) radicals, together with the effects of base sequence on the formation of the end products in runs of one, two, or three contiguous guanines. The distributions of these alkali-labile lesions were determined by gel electrophoresis methods. The cascade of events was initiated through the use of 308 nm XeCl excimer laser pulses to generate CO(3) (.-) radicals by an established method based on the photodissociation of persulfate to sulfate radicals and the oxidation of bicarbonate. Although the Saito model (Saito et al., J. Am. Chem. Soc. 1995, 117, 6406-6407) predicts relative ease of one-electron oxidations in DNA, following the trend 5'-GGG > 5'-GG > 5'-G, we found that the rate constants for CO(3) (.-) mediated oxidation of guanines in these sequence contexts (k(5)) showed only small variation within a narrow range [(1.5-3.0)x10(7) M(-1) s(-1)]. In contrast, the distributions of the end-products are dependent on the base sequence context and are higher at the 5'-G in 5'-GG sequences and at the first two 5'-guanines in the 5'-GGG sequences. These effects are attributed to a combination of initial hole distributions among the contiguous guanines and the subsequent differences in chemical reaction yields at each guanine. The lack of dependence of k(5) on sequence context indicates that the one-electron oxidation of guanine in DNA by CO(3) (.-) radicals occurs by an inner-sphere mechanism. PMID- 17335090 TI - A Type II polyketide synthase from the gram-negative Bacterium Stigmatella aurantiaca is involved in Aurachin alkaloid biosynthesis. PMID- 17335091 TI - Peptide-embedded heterocycles by mild single and multiple Aza-Wittig ring closures. PMID- 17335092 TI - The "bond-stretched invertomer" of hexafluorocyclopropane--a new type of reactive intermediate. PMID- 17335093 TI - Robust deconvolution of complex mixtures by covariance TOCSY spectroscopy. PMID- 17335094 TI - Self-assembly meets nanofabrication: recent developments in microcontact printing and dip-pen nanolithography. PMID- 17335095 TI - Structural analysis of the capsular polysaccharide from Campylobacter jejuni RM1221. AB - The complete genome of Campylobacter jejuni strain RM1221 (Penner serotype HS:53) was reported recently and contains a novel capsular polysaccharide (CPS) biosynthesis locus. Cell-surface carbohydrates such as CPS are known to be important for bacterial survival and often contribute to pathogenesis. In this study, we describe the complete structure of the CPS of C. jejuni RM1221, which was determined by using NMR spectroscopy, MS, and chemical methods. The CPS contains 6-deoxy-D-manno-heptose and D-threo-pent-2-ulose (D-xylulose), two monosaccharides that are rarely found in bacterial polysaccharides. The CPS has a regular structure of a linear main chain of trisaccharide repeating units, composed of two alpha- and one beta-6-deoxy-D-manno-heptopyranose residues, which are linked through a phosphodiester linkage. Branching residues of xylulose are incorporated nonstoichiometrically: each trisaccharide repeating unit of the main chain bears no, one, or two xylulose residues. The xylulose glycosidic linkages are extremely acid labile, and it is not clear how they can be preserved under the acidic conditions of the gastrointestinal tract, where Campylobacter resides during infection. We have also shown that the CPS biosynthesis genes of C. jejuni RM1221 are conserved in other C. jejuni strains of the Penner serotype HS:53, including serotype HS:53 reference strain RM3435. PMID- 17335097 TI - Rational manipulation of carrier-domain geometry in nonribosomal peptide synthetases. PMID- 17335096 TI - ValC, a new type of C7-Cyclitol kinase involved in the biosynthesis of the antifungal agent validamycin A. AB - The gene valC, which encodes an enzyme homologous to the 2-epi-5-epi-valiolone kinase (AcbM) of the acarbose biosynthetic pathway, was identified in the validamycin A biosynthetic gene cluster. Inactivation of valC resulted in mutants that lack the ability to produce validamycin A. Complementation experiments with a replicating plasmid harboring full-length valC restored the production of validamycin A, thus suggesting a critical function of valC in validamycin biosynthesis. In vitro characterization of ValC revealed a new type of C7 cyclitol kinase, which phosphorylates valienone and validone--but not 2-epi-5-epi valiolone, 5-epi-valiolone, or glucose--to afford their 7-phosphate derivatives. The results provide new insights into the activity of this enzyme and also confirm the existence of two different pathways leading to the same end-product: the valienamine moiety common to acarbose and validamycin A. PMID- 17335098 TI - Nucleophile selectivity of chorismate-utilizing enzymes. PMID- 17335099 TI - Cyclopenta[d]pyrimidines and dihydropyrrolo[2,3-d]pyrimidines as potent and selective corticotropin-releasing factor 1 receptor antagonists. AB - Two new classes of potent and selective CRF(1) receptor antagonists are presented. Exploration of general templates 3 and 4 through modifications of the top amine and bottom phenyl substituents led to optimization of the in vitro affinity and pharmacokinetic profiles. The typical alkyl chains present in the top region of CRF(1) antagonists were replaced by substituted heteroaryl moieties, leading to a dramatic improvement of the metabolic stability. This improvement was apparent when the compounds were dosed in vivo: several compounds exhibited low plasma clearance, good oral bioavailability, and high brain penetration. As a consequence of their outstanding pharmacokinetic profiles, these CRF(1) antagonists, as exemplified by compound 4 fi (4-(4-bromo-3-methyl-1H pyrazol-1-yl)-7-(2,4-dichlorophenyl)-2-methyl-6,7-dihydro-5H-pyrrolo[2,3 d]pyrimidine), produced a dose-dependent "anxiolytic-like" effect when administered orally, decreasing the vocalization of rat pups. PMID- 17335100 TI - The effects of pay and job satisfaction on the labour supply of hospital consultants. AB - There is little evidence about the responsiveness of doctors' labour supply to changes in pay. Given substantial increases in NHS expenditure, new national contracts for hospital doctors and general practitioners that involve increases in pay, and the gradual imposition of a ceiling on hours worked through the European Working Time Directive, knowledge of the size of labour supply elasticities is crucial in examining the effects of these major changes. This paper estimates a modified labour supply model for hospital consultants, using data from a survey of consultants in Scotland. Rigidities in wage setting within the NHS mean that the usual specification of the labour supply model is extended by the inclusion of job quality (job satisfaction) in the equation explaining the optimal number of hours worked. Generalised Method of Moments estimation is used to account for the endogeneity of both earnings and job quality. Our results confirm the importance of pay and non-pay factors on the supply of labour by consultants. The results are sensitive to the exclusion of job quality and show a slight underestimation of the uncompensated earnings elasticity (of 0.09) without controlling for the effect of job quality, and 0.12 when we controlled for job quality. Pay increases in the new contract for consultants will only result in small increases in hours worked. Small and non-significant elasticity estimates at higher quantiles in the distribution of hours suggest that any increases in hours worked are more likely for consultants who work part time. Those currently working above the median number of hours are much less responsive to changes in earnings. PMID- 17335101 TI - Atypical antipsychotics and polydipsia: a cause or a treatment? AB - Primary polydipsia (PP) is a frequent complication that affects many chronic schizophrenic inpatients. Due to possible lethal consequences, for example, hyponatremia, coma and death, it's fundamental for the physician achieving early diagnosis and treating this condition. The first step is identifying polydipsia by clinical, biochemical and pharmacological means. Nowadays, the pathophysiology of PP remains unclear, and this limits the possibility of detecting an appropriate drug treatment. Typical antipsychotics have been associated to a worsening of polydipsic behavior, while more recently atypical antipsychotics have been reported as being useful. However results are still mixed and controversial. It appears that risperidone and olanzapine are not clearly effective; clozapine may improve symptoms, although it is difficult to manage from a therapeutic point of view; quetiapine has been poorly studied so far, nonetheless it has given interesting results. Through a case study analysis, this report presents a brief, yet selective, overview of the current state of psychopharmacology in the treatment of PP with atypical antipsychotics in schizophrenia. PMID- 17335102 TI - The effect of cigarette taxes on smoking among men and women. AB - The literature contains numerous studies that estimate the effect of cigarette taxes on smoking across various population groups. Although the conclusions are split, most US studies find that men are more responsive to cigarette taxes than women. This paper shows that these results are due to the failure to control for state-specific gender gaps in smoking rates that are correlated with cigarette taxes. When gender-specific state fixed effects are included to control for these gaps, the results indicate that women are nearly twice as responsive to cigarette taxes as are men. Since the econometric specification controls for variation in the tax response by household income, it is unlikely to be responsible for the difference. PMID- 17335103 TI - Phosphinate inhibitors of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: L-lysine ligase (MurE). AB - The increasing emergence of pathogenic bacterial strains with high resistance to antibiotic therapy has created an urgent need for the development of new antibacterial agents that are directed towards novel targets. We have focused our attention on the Mur ligases (MurC-F), which catalyze the early steps of bacterial peptidoglycan biosynthesis, and which to date represent under-exploited targets for antibacterial drug design. We show that some of our phosphinate inhibitors of UDP-N-acetylmuramoyl-L-alanyl:D-glutamate ligase (MurD) also inhibits UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine ligase (MurE). To obtain new information on their structure-activity relationships, three new, structurally related phosphinates were synthesized and evaluated for inhibition of MurD and MurE. PMID- 17335104 TI - Synthesis and 5-HT2A, 5-HT1A and alpha1-binding affinities of 2-[2-Hydroxy-3 (pyridin-3-yl-methyl)amino]-, 2-[2-hydroxy-3-(2-pyridin-2-yl-ethyl)amino]- and 2 [2-hydroxy-3-(4-N-methyl-piperazin-1-yl)-amino]propoxybenzaldehyde-O (substituted) benzyl oximes. AB - Some oxime ether-substituted aryloxypropanolamines 3-5, structurally related to the active metabolite 2 of sarpogrelate 1, were synthesized and tested for their affinities at 5-HT2A and 5-HT1A serotoninergic receptors as well as at the alpha1 adrenoceptor. The results show that the compounds possess, at least partially, the ability of the model compounds 1 and 2 to interact with the 5-HT2A-receptors; they have the same selectivity towards 5-HT2A receptors vs alpha1-adrenoceptors. PMID- 17335105 TI - Synthesis and biological evaluation of new niphathesine analogues. AB - Niphathesine C and related pyridine alkaloids are well known natural products with interesting antimicrobial activities, characterized by a pyridine ring and a lipophilic side chain with a terminal nitrogen-containing functional group. This paper describes the synthesis of analogues of these alkylpyridine alkaloids with variation of the heterocyclic ring and the terminal functional group. Key steps of the syntheses are a Sonogashira reaction of appropriate aryl iodides with undec-10-ynol or undec-10-ynoic acid derivatives. The resulting compounds were tested in an agar diffusion assay against several bacteria and fungi. PMID- 17335106 TI - Correlation between prenatal ultrasound and fetal autopsy findings in fetal anomalies terminated in the second trimester. AB - OBJECTIVE: The aim of the study was to compare the consistency of major/minor fetal anomalies detected by second trimester prenatal ultrasound examination with the findings in fetal autopsies following the termination of pregnancy (TOP) in the second trimester. DESIGN: In a 4-year long prospective study, 107 second trimester TOP was performed due to fetal malformation diagnosed by second trimester-ultrasound examination at a tertiary referral center. Ultrasound findings were compared with fetal autopsy findings. RESULT: Of the 107 cases with major fetal anomalies diagnosed by prenatal ultrasound, 49% had central nervous system anomalies, 23% had kidney and urinary tract anomalies, 11% had congenital heart disease. All of these major anomalies leading to TOP were confirmed by fetal autopsy (100% success rate in major anomalies). Overall success rate in prenatal ultrasound for major and minor anomalies was 77%. The percentage of additional minor anomalies detected in fetal autopsies was 20%. Three percent of the minor anomalies detected by prenatal ultrasonography could not be confirmed during autopsy. Chromosomal anomalies were detected in 9 (16%) out of 57 cases. CONCLUSION: Evaluation of fetal autopsies following TOP enables diagnosis of pathologies undetected by prenatal ultrasound alone, leading to better preconceptional counseling for subsequent pregnancies. PMID- 17335107 TI - Self-association based on interfacial structured water leads to {Mo154}approximately 1165 super clusters: a dielectric study. PMID- 17335108 TI - Modeling attainment of steady state of drug concentration in plasma by means of a Bayesian approach using MCMC methods. AB - The approach of Bayesian mixed effects modeling is an appropriate method for estimating both population-specific as well as subject-specific times to steady state. In addition to pure estimation, the approach allows to determine the time until a certain fraction of individuals of a population has reached steady state with a pre-specified certainty. In this paper a mixed effects model for the parameters of a nonlinear pharmacokinetic model is used within a Bayesian framework. Model fitting by means of Markov Chain Monte Carlo methods as implemented in the Gibbs sampler as well as the extraction of estimates and probability statements of interest are described. Finally, the proposed approach is illustrated by application to trough data from a multiple dose clinical trial. PMID- 17335109 TI - Anion and cation effects on imidazolium salt melting points: a descriptor modelling study. AB - The challenge of predicting the melting point of ionic liquids is outlined. A descriptor modelling approach for two separate sets of ionic liquids is presented. In each case, the cations and the anions are modelled separately, using quantitative structure-property relationships. Both models include constitutional, topological and geometric descriptors as well as quantum mechanical ones. This approach gives access to (nxm) ionic liquids using only (n+m) calculations. The protocol is tested and validated for predicting the melting points of two sets, comprised of 22 and 62 imidazolium-based ionic liquids, respectively. Good correlations and predictions are obtained in both cases. Within the data set selected (only monopositive and mononegative ions are studied, and so total charge was not a factor), the degree of sphericity is the most important variable for the anion, while for the cation the main descriptors pertained to three radial distribution functions that describe three different sections in the cation. These characterise the ionic interactions, the symmetry breaking region, and the length of the side chains. PMID- 17335110 TI - Characterization of pericyclic reactions using multicenter electron delocalization analysis. AB - This work investigates the applicability of multicenter delocalization analysis to the characterization of pericyclic reactions. The results indicate that multicenter delocalization indices are a powerful tool for studying concerted processes, allowing the characterization of aromatic transition states with a significant increase in the electron delocalization. Moreover, an advantage over magnetic-based indices is that multicenter delocalization indices are not influenced by local electron currents but by the electron delocalization along the multiple (n) centers, and provide, in a quantitative sense, more reliable results. A thorough comparison with magnetic-based indices is carried out for the trimerization reaction of acetylene. Tracking the values of multicenter delocalization indices along the reaction path allows investigation of the nature of concerted mechanisms. Six-center electron delocalization displays a maximum at the transition state of the Diels-Alder reaction, whereas a similar maximum of four-center electron delocalization is slightly displaced to butadiene for the ring opening of cyclobutene. The profile of multicenter electron delocalization indices along the reaction path of [2+2] cycloaddition of ketene to ethene shows the presence of the two independent mechanisms that agree with the two HOMO/LUMO orbital interactions previously proposed to dominate this reaction. PMID- 17335111 TI - The cyclohexasilanes Si6H11X and Si6Me11X with X=F, Cl, Br and I: a quantum chemical and Raman spectroscopic investigation of a multiple conformer problem. AB - The conformers of the monohalocyclohexasilanes, Si(6)H(11)X (X=F, Cl, Br or I) and the haloundecamethylcyclohexasilanes, Si(6)Me(11)X (X=F, Cl, Br or I) are investigated by DFT calculations employing the B3LYP density functional and 6 31+G* basis sets for elements up to the third row, and SDD basis sets for heavier elements. Five minima are found for Si(6)H(11)X-the axial and equatorial chair conformers, with the substituent X either in an axial or equatorial position-and another three twisted structures. The equatorial chair conformer is the global minimum for the X=Cl, Br and I, the axial chair for X=F. The barrier for the ring inversion is approximately 13 kJ mol(-1) for all four compounds. Five minima closely related to those of Si(6)H(11)X are found for Si(6)Me(11)X. Again, the equatorial chair is the global minimum for X=Cl, Br and I, and the axial chair for X=F. Additionally, two symmetrical boat conformers are found as local minima on the potential energy surfaces for X=F, Cl and Br, but not for X=I. The barrier for the ring inversion is approximately 14-16 kJ mol(-1) for all compounds. The conformational equilibria for Si(6)Me(11)X in toluene solution are investigated using temperature dependent Raman spectroscopy. The wavenumber range of the stretching vibrations of the heavy atoms X and Si from 270-370 cm(-1) is analyzed. Using the van't Hoff relationship, the enthalpy differences between axial and equatorial chair conformers (H(ax-)H(eq.)) are 1.1 kJ mol(-1) for X=F, and 1.8 to 2.8 kJ mol(-1) for X=Cl, Br and I. Due to rapid interconversion, only a single Raman band originating from the "averaged" twist and boat conformers could be observed. Generally, reasonable agreement between the calculated relative energies and the experimentally determined values is found. PMID- 17335112 TI - Pivotal steps towards quantification of molecular diffusion coefficients by NMR. AB - Using nuclear magnetic resonance (NMR) spectroscopy with a pair of pulsed field gradients (PFGs), Stajeskal and Tanner successfully measured molecular diffusion coefficients in solution in 1965. This method has since been used extensively in various applications, especially after the PFG was implemented in commercial NMR probes. Due to the nonuniformity of the PFG and radio frequency (RF) fields, molecules distributed throughout the sample experience different PFG and RF fields and contribute unevenly to the measured diffusion coefficients, resulting in considerable errors in conventional NMR diffusion experiments. By selective excitation of a central sample region with an offset-independent adiabatic inversion pulse and a PFG, a uniform RF field can be assumed, and the PFG can be represented as a linear approximation. Under these conditions, the molecules diffuse as if they were all experiencing the same effective gradient g(e), leading to a Gaussian signal decay as a function of the PFG strength. Quantitative measurement of molecular diffusion coefficients is therefore made possible. From the diffusion coefficient of a 90 % H(2)O/10 % D(2)O sample, it is convenient to calibrate g(e) with a Java program. In a similar way the nonlinearity of the PFG can be corrected. PMID- 17335113 TI - Chemistry in confined geometries: reactions at an organic surface. PMID- 17335115 TI - Antipromastigote activity of the malabaricones of Myristica malabarica (rampatri). AB - A major problem in the management of visceral leishmaniasis, especially in the Indian subcontinent, is the growing unresponsiveness to conventional antimonial therapy, indicating the urgent need to identify new antileishmanial compounds. This study was undertaken to evaluate the antileishmanial activity of the fruit rind of Myristica malabarica that is used as a spice and is also credited with medicinal properties. The antipromastigote activity of different extracts/fractions of M. malabarica and its constituent diarylnonanoids were evaluated in Leishmania donovani promastigotes (MHOM/IN/83/AG83) using the MTS PMS assay. Preliminary screening of the ether extract (R1) with its crude methanol fraction (R2) and two fractions (R3 and R4) revealed that R2 had potent leishmanicidal activity (IC(50) 31.0 microg/mL), whereas R3 and R4 showed poor activity. Fractionation of R2 yielded four diarylnonanoids (malabaricones A-D, designated as Mal A, Mal B, Mal C and Mal D, respectively). The IC(50) values of Mal A-D were 16, 22, 27 and >50 microg/mL, respectively. Taken together, the data suggest that the methanol extract of M. malabarica, especially its constituent compounds, Mal A and Mal B, have promising antileishmanial activity meriting further investigations regarding the underlying molecular mechanism(s) of action with a view towards future drug development. PMID- 17335114 TI - Analgesic, antipyretic and Ulcerogenic properties of an indigenous formulation- Kalpaamruthaa. AB - A modified indigenous Siddha formulation Kalpaamruthaa (KA), containing Semecarpus anacardium nut milk extract (SA), dried powder of Emblica officinalis (EO) fruit and honey was evaluated for its analgesic, antipyretic and Ulcerogenic properties. Both SA and KA, at a dose of 150 mg/kg b. wt were compared with the standard drug diclofenac sodium. KA exhibited an enhanced effect on all properties compared with that found with sole SA treatment, and is likely to be due to synergistic and additive interactions within the complex mixture of phytochemicals present in KA. PMID- 17335116 TI - Spirulina did not ameliorate idiopathic chronic fatigue in four N-of-1 randomized controlled trials. AB - Idiopathic chronic fatigue is an exclusion diagnosis established when no chronic disease is found. Spirulina platensis is an alga with a rich content of proteins, vitamins, minerals and amino acids and is considered as a bioactive additive with multiple effects, among them being effects against fatigue. However, despite the worldwide utilization of Spirulina, there are only a few quality studies with it and none concerning fatigue. The N-of-1 randomized trials are made on one patient, and by this kind of study the efficacy of a treatment on that particular patient can be assessed. A series of four N-of-1 double-blind, randomized trials were performed on four physicians who complained of chronic fatigue. Each patient was his own control and received three pairs of treatments comprising 4 weeks of spirulina and 4 weeks of placebo. Spirulina platensis was administered in a dose of 3 g/day. For each pair, the order of treatments was randomized. Outcome measures were severity of fatigue measured on a 10-point scale. The scores of fatigue were not significantly different between spirulina and placebo. Spirulina administered in a dose of 3 g/day did not ameliorate fatigue more than the placebo in any of the four subjects, and possibly it has no effect on chronic fatigue. PMID- 17335117 TI - Modulation of P-glycoprotein-mediated resistance by kaempferol derivatives isolated from Zingiber zerumbet. AB - This study examined the effects of the kaempferol derivatives extracted from Zingiber zerumbet on the accumulation and efflux of [(3)H]-daunomycin (DNM) in P glycoprotein (P-gp) overexpressing multidrug resistant (MDR) human breast cancer cells, MCF-7/ADR. Of six kaempferol derivatives extracted from Z. zerumbet, kaempferol-3-O-methyl ether (1) and kaempferol-3,4'-O-dimethyl ether (2) showed a potent P-gp inhibitory effect as great as verapamil, a well-known P-gp inhibitor. The P-gp inhibitory activity of these two compounds was through a 3-fold increase of the level of [(3)H]-DNM accumulation and a decrease of P-gp-mediated efflux. These results suggest that the kaempferol derivative components of Z. zerumbet can be used as a scaffold for developing agents that reverse P-gp-mediated MDR in human cancer chemotherapy. PMID- 17335118 TI - A fraction of Acorus calamus L. extract devoid of beta-asarone enhances adipocyte differentiation in 3T3-L1 cells. AB - The effects of fractions partitioned from the ethanol extract of Acorus calamus L. (AC) on adipocyte differentiation were investigated using cultured mouse 3T3 L1 preadipocytes. The degree of differentiation was evaluated by measuring the cellular triglycerides and protein expression of the glucose transporter GLUT4 in 3T3-L1 cells. The ethyl acetate fraction of the AC extract (ACE) was found to enhance adipocyte differentiation as did rosiglitazone. The results of further fractionation of ACE indicated that the active fraction does not consist of beta asarone, which is a toxic component of this plant. This finding suggests that ACE has potential insulin-sensitizing activity like rosiglitazone, and may improve type 2 diabetes. PMID- 17335119 TI - Boom and bust from influenza. PMID- 17335120 TI - Automated time series forecasting for biosurveillance. AB - For robust detection performance, traditional control chart monitoring for biosurveillance is based on input data free of trends, day-of-week effects, and other systematic behaviour. Time series forecasting methods may be used to remove this behaviour by subtracting forecasts from observations to form residuals for algorithmic input. We describe three forecast methods and compare their predictive accuracy on each of 16 authentic syndromic data streams. The methods are (1) a non-adaptive regression model using a long historical baseline, (2) an adaptive regression model with a shorter, sliding baseline, and (3) the Holt Winters method for generalized exponential smoothing. Criteria for comparing the forecasts were the root-mean-square error, the median absolute per cent error (MedAPE), and the median absolute deviation. The median-based criteria showed best overall performance for the Holt-Winters method. The MedAPE measures over the 16 test series averaged 16.5, 11.6, and 9.7 for the non-adaptive regression, adaptive regression, and Holt-Winters methods, respectively. The non-adaptive regression forecasts were degraded by changes in the data behaviour in the fixed baseline period used to compute model coefficients. The mean-based criterion was less conclusive because of the effects of poor forecasts on a small number of calendar holidays. The Holt-Winters method was also most effective at removing serial autocorrelation, with most 1-day-lag autocorrelation coefficients below 0.15. The forecast methods were compared without tuning them to the behaviour of individual series. We achieved improved predictions with such tuning of the Holt Winters method, but practical use of such improvements for routine surveillance will require reliable data classification methods. PMID- 17335121 TI - The misuse of count data aggregated over time for disease mapping. AB - The ongoing spread of spatial analysis techniques for small areas has facilitated the publication of mortality and morbidity Atlases based on time periods that group information spanning several years. Although this is a widespread practice, this paper proves that the use of count data aggregated over time for disease mapping may give inappropriate area-specific relative risk. As a result, both decision-making and healthcare policies could be affected by inappropriate model specifications using aggregated information over time. The Poisson distribution properties were used in order to quantify the bias in area-specific relative risk estimation due to count data aggregated over time. A hierarchical Bayesian model with spatio-temporal random structure is proposed as an alternative to smoothing relative risk if the period of study need to span several years. Methods discussed in this paper were applied to a small-area survey on male mortality from all causes in Southern Spain for the period 1985-1999. The results suggest that particular caution should be taken when interpreting risk maps based on clustered annual data that use models with no temporal structure to smooth out the rates. PMID- 17335122 TI - Early versus late surgical drainage for obstructive pancreatitis in an experimental model. AB - BACKGROUND: Chronic pancreatitis (CP) is characterized by intractable abdominal pain, and pancreatic exocrine and endocrine dysfunction. This study investigated whether early surgical drainage of pancreatic duct obstruction leads to improved recovery of pancreatic function compared with late surgical drainage in an experimental model of chronic obstructive pancreatitis. METHODS: Twenty-one piglets underwent pancreatic duct ligation and subsequent longitudinal pancreaticojejunostomy after 3 weeks (early drainage) or 6 weeks (late drainage), and drainage continued for 6 weeks. In controls with CP pancreatic duct ligation was continued for 12 weeks without a drainage procedure. RESULTS: Histological pancreatitis scores decreased with early drainage (P = 0.005), but not with late drainage. Pancreatic secretion of amylase and lipase was restored after early but not late drainage (P = 0.003 and P = 0.048 respectively). Excretion levels of lipase were restored to near-baseline preligation levels after early drainage. Pancreatic endocrine function (glucose tolerance test) showed no insufficiency in either group. CONCLUSION: In this model of early versus late surgical drainage of obstructive pancreatitis, histology grades and pancreatic exocrine function showed improvement in the early drainage group but no recovery in the late drainage group. PMID- 17335123 TI - Venous changes and lymphoedema 4 years after axillary surgery for breast cancer. PMID- 17335124 TI - Relaxation of the isolated human internal anal sphincter by sildenafil. AB - BACKGROUND: Hypertonicity of the internal anal sphincter (IAS) appears to be involved in the pathogenesis of anal fissure. The relaxant effects of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on isolated human IAS were investigated. METHODS: The efficacy (maximal effect, E(max)) and potency (-log IC(50), where IC(50) is half-maximal inhibitory concentration) of the PDE5 inhibitors, sildenafil and zaprinast, and of nitric oxide donors, sodium nitroprusside and glyceryl trinitrate, as relaxants of histamine (0.1 mmol/l) induced tone were examined in IAS strips under isometric contraction. The presence of PDE5 isoenzymes and changes in intracellular calcium and cyclic nucleotide levels in IAS muscle were tested by real-time reverse transcriptase polymerase chain reaction, epifluorescence microscopy and enzyme immunoassay respectively. RESULTS: Sildenafil produced a concentration-related inhibition of the mean(s.e.m.) histamine-induced tone (E(max) 83(2) per cent, - log IC(50) 7.04(0.05); n = 12). Zaprinast produced relaxation to similar degree, but with lower potency. Nitric oxide donors also relaxed IAS. Sildenafil (1 micromol/l) produced a 1.8-fold increase in guanosine 3',5'-cyclic monophosphate content, with no change in adenosine 3',5'-cyclic monophosphate levels. Sildenafil markedly depressed the peak intracellular calcium increase evoked by histamine. PDE5A1, PDE5A2 and PDE5A3 transcripts were expressed in IAS muscle. CONCLUSION: Sildenafil relaxes the augmented tone of human IAS in vitro. These results support the potential use of this PDE5 inhibitor in the treatment of chronic anal fissure. PMID- 17335125 TI - Local excision of rectal tumours by transanal endoscopic microsurgery. AB - BACKGROUND: Transanal endoscopic microsurgery (TEM) allows locally complete excision of rectal tumours and provides an alternative to conventional surgery for benign tumours. However, its role in the curative treatment of invasive carcinoma is controversial. The aim of this study was to determine the morbidity and long-term results for rectal tumours excised by TEM. METHODS: Between February 1993 and January 2005, 200 patients underwent TEM for excision of adenomas (148) or carcinomas (52). The median tumour distance from the anal verge was 8 (range 1-16) cm. RESULTS: Mortality and morbidity rates were 0.5 and 14.0 per cent respectively. At a median follow-up of 33 (range 2-133) months, local recurrence had developed in 11 patients (7.6 per cent) with an adenoma. Histological examination of carcinomas revealed pathological tumour (pT) stage 1 in 31 patients, pT2 in 17 and pT3 in four. Immediate salvage surgery was performed in seven patients (13 per cent). At a median follow-up of 34 (range 1 102) months, eight patients (15 per cent) with carcinomas had developed local recurrence. The overall and disease-free 5-year survival rates for patients with carcinomas were 76 and 65 per cent respectively. CONCLUSION: TEM is an appropriate surgical treatment option for benign rectal tumours. For carcinomas, it is oncologically safe provided that resection margins are clear, but strict patient selection is required. PMID- 17335126 TI - Strategy for characterization of paraproteins in the diagnosis of malignant monoclonal gammapathies. PMID- 17335127 TI - Emerging role of target-based therapies for gastrointestinal malignancies. PMID- 17335128 TI - Alternative interventional multimodality therapies for the management of liver malignancies. AB - Primary and secondary liver tumors are highly malignant with a very high morbidity and mortality. Although surgical resection is generally accepted as the mainstay of treatment, only a small number of patients are suitable for curative resection. Interventional multimodality therapies provide an alternative to liver resection with minimal morbidity and mortality and quite promising outcomes. These include transcatheter arterial chemoembolization (TACE), percutaneous ethanol (PEI) or other injection techniques, radiofrequency ablation (RFA), microwave coagulation therapy (MCT), cryoablation and interstitial laser photocoagulation (ILP). Techniques, indications and outcomes are discussed. PMID- 17335129 TI - New options in the treatment of myelodysplastic syndrome. AB - Myelodysplastic syndrome (MDS) is a heterogeneous group of progressive chronic hematopoietic disorders, usually presenting as refractory anemia or cytopenia, with an approximately 25% risk of progression toward acute myeloid leukaeima (AML), and no proven curative treatment. Novel biological treatment strategies targeting both the malignant blood cell and its microenvironment can overcome resistance to current therapies, and represent a promising treatment paradigm for improving patient outcome. Many of these agents have multiple biologic activities. The objective of this article is to present a comparative review of classification systems in MDS and to discuss the evolving trends in the treatment of MDS (immunosuppresive therapy, immunomodulatory drugs, arsenic trioxide, proteasome inhibitors, epigenetic therapy). PMID- 17335130 TI - Good Scientific Practice. Part VII. Underpublishing/underreporting research. PMID- 17335131 TI - Irinotecan plus weekly 5-fluorouracil and leucovorin as salvage treatment for patients with metastatic colorectal cancer: A phase II trial. AB - PURPOSE: A phase II study was conducted to evaluate the toxicity and efficacy of irinotecan (CPT-11), 5-fluorouracil/leucovorin (5-FU/LV) (AIO regimen) as salvage treatment in patients with metastatic colorectal cancer (MCC). PATIENTS AND METHODS: Thirty-three patients relapsing after oxaliplatin-based first line chemotherapy were enrolled. There were 20 males and 13 females with median age of 69 years and WHO performance status (PS) of 0, 1, and 2 in 15, 16 and 2 patients, respectively. CPT-11 was administered on day 1 at 80 mg/m(2) in 60 min i.v. infusion, then LV (500 mg/m(2)) on day 1 as a 2h i.v. infusion, followed by 5-FU (2.600 mg/m(2)) as a 22h i.v. infusion. Treatment was repeated weekly for 6 consecutive weeks, in cycles of 7 weeks (one week rest). RESULTS: All patients were evaluable for toxicity and response. Complete response (CR) was achieved in 2 (6%) patients and partial response (PR) in 4 (12%) (over-all response rate - ORR: 18%, 95% C.I.: 5.95-35.43); 13 patients (40%) had stable disease (SD) and 14 (42%) progressive disease (PD). After a median follow up period of 9 months the median duration of response was 5 months, the median time to tumor progression (TTP) 7.5 months and the median overall survival (OS) 14 months. Grade 3 and 4 neutropenia occured in 13 (39%) patients, febrile neutropeina in 3 (9%), and grade 4 thrombocytopenia in one (3%). Grade 3/4 diarrhea occured in 12 (36%) patients, grade 3/4 neurotoxicity in 3 (9%), and grade 3 asthenia in 4 (12%). There was no treatment-related death. CONCLUSION: The combination of weekly CPT 11 and infusional 5-FU/LV is an active and relatively well-tolerated regimen as salvage treatment in MCC. PMID- 17335132 TI - Primarily tamoxifen-unresponsive, steroid receptor-positive breast cancer may respond to an aromatase inhibition: a pilot study. AB - PURPOSE: Breast carcinomas becoming tamoxifen-resistant after objective clinical response to antiestrogen therapy may remain responsive to other endocrine agents due to different mechanisms of action. The aim of our study was to analyze whether primarily tamoxifen-unresponsive/steroid receptor (SR) - positive breast carcinomas can respond to an aromatase inhibition. PATIENTS AND METHODS: Thirteen postmenopausal, SR-positive, metastatic breast cancer (MBC) patients were included: they had previously failed to respond to tamoxifen, either as primary systemic therapy for advanced disease, or as adjuvant treatment (5 and 8 patients, respectively). Patients were treated with 2.5 mg letrozole daily, from 2-25 months, mostly until disease progression. RESULTS: Partial response (PR) was obtained in one third of the patients (4/13); additionally, 3 patients showed disease stabilization (SD) longer than 6 months. The observed response duration lasted from 7 to 36+ months (median 9). Overall survival from the beginning of letrozole treatment was better in letrozole responders compared with nonresponders. It appeared as if there were two different subgroups of patients: one completely endocrine-unresponsive, and the other unresponsive to tamoxifen but responsive to letrozole (supposed to be primarily tamoxifen-resistant, but otherwise endocrine-responsive). HER-2 overexpression (immunohistochemically determined as 2+ and 3+) was found in 3 patients, which could not account for the different endocrine responsiveness. CONCLUSION: Our study confirmed that some SR positive breast carcinomas, primarily tamoxifen-unresponsive, may respond to letrozole, thus being endocrine-responsive, while others did not respond, probably due to complete endocrine unresponsiveness. It is not likely that HER-2 was the biomarker that made the difference between these two subgroups. PMID- 17335133 TI - beta(2)-microglobulin in Hodgkin's lymphoma: prognostic significance in patients treated with ABVD or equivalent regimens. AB - PURPOSE: Serum beta-2 microglobulin (sbeta(2)m) is an established prognostic factor for several lymphoproliferative disorders. Because its significance in Hodgkin's lymphoma (HL) is controversial, we determined sbeta(2)m levels in pretreatment serum samples of patients with HL in order to elucidate its prognostic value in this condition. PATIENTS AND METHODS: Pretreatment sbeta(2)m levels were determined in 379 HL patients who were treated with ABVD or equivalent regimens with or without radiotherapy (RT), using a radioimmunoassay (upper normal limit 2.4 mg/l). Sbeta(2)m levels were correlated with several clinical and laboratory parameters. RESULTS: Elevated sbeta(2)m levels were detected in 138/379 (36%) patients and correlated with all clinical and laboratory baseline features except gender, lung involvement and mediastinal bulk. They also correlated with serum soluble CD30 and interleukin-10 levels. The 8-year failure-free survival (FFS) was 78 -/+ 4% for patients with normal versus 65 -/+ 7% for patients with elevated sbeta(2)m levels (p=0.003). The corresponding rates among early-stage patients were 83 -/+ 53% versus 71 -/+ 9% (p=0.003), while for advanced stages they were 70 -/+ 6% versus 64 -/+ 8% (p=0.54). In multivariate analysis of the whole patient population elevation of sbeta(2)m levels was not predictive of FFS, but it was strongly predictive among early-stage patients. The 8-year overall survival (OS) rates were 91 -/+ 3% for patients with normal versus 59 -/+ 11% (p <0,0001) for patients with elevated sbeta(2)m levels, while unrelated mortality at 8 years was 1 -/+ 1% versus 27 -/+ 12% (p<0.0001). CONCLUSION: Our data suggest that sbeta(2)m levels may be a potent prognostic factor for FFS in patients with early stage HL treated with ABVD and equivalent regimens. Their effect on OS is confounded by the higher unrelated mortality in patients with elevated baseline sbeta(2)m levels, probably due to the strong association between sbeta(2)m and older age. PMID- 17335134 TI - Breast cancer following curative chemotherapy for non-Hodgkin's lymphoma and the effect of drug resistance proteins to the final outcome. A retrospective study. AB - PURPOSE: To investigate the overall survival (OS) of patients developing breast cancer (BC) after curative chemotherapy for non-Hodgkin's lymphoma (NHL) and to evaluate the possible effect on the patients' outcome of the expression of drug resistance-related proteins (P-glycoprotein-Pgp, multidrug resistance-associated protein-MRP, and multidrug resistance-related vault lung resistance protein-LRP) in BC issue. PATIENTS AND METHODS: STUDY GROUP: 25 female patients (median age 60 years, range 37-70) who developed BC after chemotherapy for high/intermediate grade B-cell NHL, treated with CHOP and achieving complete remission (CR). This group was further subdivided in subgroups A and B, according to the time interval between NHL and BC development ( 24 months, respectively). A matched pair group of de novo BC patients formed the control group. BC tissue was immuno histochemically stained for Pgp, MRP and LRP. RESULTS: The median interval between NHL diagnosis and BC development was 26 months (range 9-49). In both groups 14 patients had tumor grade II; 16 were negative for steroid receptors; 17 overexpressed c-erbB-2; 14 were stage IIIA/B, and 11 stage IV. CMF or CNF (mitoxantrone instead of doxorubicin) were given for BC. Early progression was noticed in all study group patients for which second-line chemotherapy was instituted. There was a better response for stage IV patients in the control versus the study group (p=0.07). More prolonged OS was demonstrate for patients with stage III in the control group (median 51 months) and in subgroup B (median 47 months) than in subgroup A (median 16 months; p=0.00012), as well as for patients with advanced disease (p=0.0045). Development of BC < 24 months after NHL resulted in reduced OS (p=0.017). No difference was noticed in the expression of drug resistance proteins between the study and control group or between subgroups A and B. CONCLUSION: BC developing shortly after a CR to NHL is an aggressive disease variant with minimal potential for response to conventional chemotherapy. Analysis of Pgp, MRP and LRP failed to demonstrate significant difference between the study and control group, although indications exist that drug resistance mechanisms might be part of the aggressive disease phenotype, contributing to the poor outcome. PMID- 17335135 TI - Does epirubicin affect left ventricular systolic performance in oncologic patients? AB - PURPOSE: In the present study the left ventricular diastolic and systolic functions were evaluated in patients treated with lower total doses of epirubicin using Doppler echocardiography. PATIENTS AND METHODS: Seventeen patients with different malignant tumors treated with epirubicin up to 450 mg/m(2) (study group), and a gender-and age-matched group of 29 patients diagnosed with tumors, who had not started treatment yet (control group), were assessed by echocardiography. Left ventricular diastolic function was assessed by measuring the Doppler transmitral flow. We measured the maximal velocity of the E wave (rapid filling) and A wave (atrial filling). The ratio of Emax/Amax, the pressure half time (PHT) of the E wave and the iso-volumic relaxation time (IVRT) were also calculated. The left ventricular systolic performance was assessed by measuring the global ejection fraction (EF). RESULTS: The left ventricular diastolic performance was altered in the study group. In this group we noticed a significant decrease ( p < 0.001) of Emax. A wave was significantly increased in the study group compared to the control group ( p < 0.001). The mitral E/A ratio was subunitary in the study group. The E wave PHT was prolonged in the epirubicin treated group in comparison to the controls (p<0.001). The IVRT was prolonged in the study group in comparison to the controls (p<0.05). The left ventricular systolic performance was not significantly altered in the study group compared to the control group. Although the EF was lower in the study group the difference did not reach statistical significance. CONCLUSION: Our Doppler echocardiography study documented an impaired left ventricular diastolic performance in patients with various malignancies treated with lower total doses of epirubicin. This impairment is due to poor left ventricular compliance. PMID- 17335136 TI - Correlation of tissue transglutaminase expression on breast cancer tissue with time to relapse, overall survival, and clinical and molecular prognostic factors: a preliminary report. AB - PURPOSE: To correlate tissue transglutaminase (TTG) expression with the expression of molecules with prognostic significance in breast cancer patients and with classical clinical parameters (disease stage, histological grade, overall survival (OS), relapse rate, disease progression and time to treatment failure-TTF). PATIENTS AND METHODS: Paraffin-embedded tissue specimens from 68 breast cancer patients were studied retrospectively for TTG expression, estrogen (ER) and progesterone (PG) receptors, c-erbB-2, p53, Bcl-2, and Ki-67. Sixty seven patients were females (mean age 60.5 years). Histology was ductal carcinoma in 53 (inflammatory in 2 and mucinous in 1 of them), lobular in 13 and tubular in 2 cases. Grade was 1 and 2 in 45 cases and 3 in 23. Forty-six patients had early stage disease (I - IIB) and 22 advanced (IIIA - IV). RESULTS: Fifty patients had at least 1 favorable molecular prognostic factor while all but 3 had at least 1 unfavorable prognostic factor. Twenty-nine (42.6%) patients have relapsed so far (mean TTF 31.4 months). Fifty-two (76.5%) patients are still alive (mean OS 38.5 months). Of the 59 patients with nodal and/or metastatic disease 54 were expressing TTG and 32 Bcl-2. Five were not expressing either one while 22 were expressing both. Of the 9 patients without nodal and/or metastatic disease all but one were expressing TTG and Bcl-2. Analyzing these subgroups of patients there was sufficient evidence that TTG expression was correlated with a trend for prolonged survival both in patients with localized and extensive disease, while the coexpression with Bcl-2 was correlated with a trend for prolongation of TTF and OS, both in relapsing and nonrelapsing patients. However, these differences did not reach statistical significance. Similar comparisons of TTG expression with the presence of adverse prognostic factors verified a beneficial effect of TTG expression on OS in all subgroups. CONCLUSION: Our data suggest that TTG is an independent favorable prognostic factor for survival, possibly enhancing the apoptotic effect of chemotherapy. PMID- 17335137 TI - Octreotide neutralizes dexamethasone antitumor actions on P388 murine lymphocytic leukemia in vivo. AB - PURPOSE: A wide variety of human malignancies, including lymphoproliferative neoplasms, express somatistatin (SS) receptors (SS-R). SS induces apoptosis and exerts pronounced antiproliferative effects on various human tumors cell lines, human xenografts, and animal tumors including P388 lymphocytic leukemia. In patients with thymoma the combination of octreotide (OCT) with corticosteroids improves the overall response rate. It has been reported that SS can increase glucocorticoid activity. Hereby, we studied the in vitro and in vivo activity of the SS analogue OCT and of the glucocorticoid dexamethasone (DEX) alone or in combination against the murine P388 lymphocytic leukemia. MATERIALS AND METHODS: Cultures of P388 lymphocytic leukemia and BDF(1) male mice implanted with P388 cells where used for the in vitro an in vivo evaluation of the antileukemic activity of SS and DEX. RESULTS: OCT induced a moderate and DEX a satisfactory cytostatic effect in vitro. OCT produced borderline antileukemic effect when administered on days 1-5 while DEX was effective in all schemes and routes of administration. However, none of the combination schemes exerted any anti leukemic activity both in vitro and in vivo. CONCLUSION: Since both SS and glucocorticoids exert direct (via receptors) and indirect antitumor actions (regulation of growth factor activity) on several cell lines, in vitro and in vivo, it becomes obvious that further in vitro studies shall provide the molecular evidence for the signal transduction pathways which are involved in the interactions of such important anticancer drugs. Based on the results of the present study, the simultaneous use of these drugs in clinical practice should be carefully considered. PMID- 17335138 TI - Does pentoxifylline increase radiation response of Ehrlich mammary carcinoma in mice? AB - PURPOSE: The presence of hypoxic cells in solid tumors is generally considered as a limiting factor for the complete control of tumors by radiation therapy. Pentoxifylline is a methylxanthine derivative that produces hemorrheologic effects which increase tissue oxygen levels. In this study we aimed to determine whether pentoxifylline would enhance the radiation response of Ehlrich mammary carcinoma in mice. MATERIALS AND METHODS: Ehrlich mammary carcinoma cells were subcutaneously transplanted into the nape of 27 male Balb/c mice. Twelve animals were injected with 50 mg/kg of pentoxifylline intraperitoneally (i.p.) and irradiated 30 min after the administration (study group). Fifteen mice were irradiated without receiving pentoxifylline (control group). All animals were exposed to a single dose of 40 Gy with Co60 gamma rays locally to the tumor site. The effect of pentoxifylline was assessed by the reduxtion rate in tumor volume (mm(3)) which was measured at least 3 times a week until mice were dead. RESULTS: The reduxtion rate of tumor volume on day 4, relative to the initial volume, was 42% in the control group and 61.6% in the study group (p=0.24). The survival of mice in the two groups was not significantly different (p=0.08). CONCLUSION: Although the reduction rate of tumor volume was higher in the study group, the difference was not statistically significant. Pentoxifylline can not be considered as a radiation enhancer in Ehrlich mammary carcinoma. PMID- 17335139 TI - Evaluation of sister chromatid exchanges, micronuclei, and proliferating rate index in hospital workers chronically exposed to ionizing radiation. AB - PURPOSE: The aim of this study was to determine the incidence of sister chromatid exchanges (SCE), micronuclei (MN) and proliferation rate of harvested lymphocytes obtained from medical stuff professionally exposed to low-dose ionizing radiation. The influence of tobacco smoking status and working conditions as confounding factors were also investigated. PATIENTS AND METHODS: Thirty subjects chronically exposed to low-dose ionizing radiation were examined (12 workers in the radiotherapy unit and 18 workers in the cardiology unit), and were compared to 15 unexposed healthy volunteers. There were 18 nonsmokers and 12 smokers among the exposed workers and 8 nonsmokers and 7 smokers among the control group. Standard cytokinesis-block MN assay, the SCE assay, and the proliferating index (PI) rate were analyzed. RESULTS: An increased frequency of SCE and MN in occupationally exposed workers were found compared to unexposed individuals. The PI was significantly lower in occupationally exposed workers in comparison to the control group. In relation to the working conditions, a significantly higher number of MN in the group of workers in the radiology unit compared to the control was found (p=0.03). The frequency of SCE was increased in occupationally exposed smokers compared with nonsmoking workers (p=0.005). Smokers in the control and radiation exposed group had lower MN frequency contrary to nonsmokers in both groups. CONCLUSION: The obtained results show higher incidence of SCE and MN in the exposed groups compared to the controls. Cigarette smoking and working conditions as confounding factors should be included into genetic monitoring studies assessing the risk associated with low-level radiation exposure. PMID- 17335140 TI - Preliminary study of mononuclear phagocytosis during breast cancer therapy. AB - PURPOSE: To evaluate the eventual changes in the number and phagocytic functions of blood monocytes in breast cancer patients during surgical treatment and chemotherapy. MATERIALS AND METHODS: The absolute and relative number of peripheral blood leukocytes and monocyte phagocytic functions were determined at the time of diagnosis (I), following surgery (II), during (III) and after chemotherapy (IV) in 30 patients diagnosed with breast cancer. The control group consisted of 30 age-matched healthy women. RESULTS: The mean number of monocytes was significantly lower in cancer patients at diagnosis, while they increased following surgery reaching the control values. There were no postchemotherapy changes in the number of monocytes. Monocyte phagocytic activity was decreased at the time of diagnosis. Following surgery, the capacity of phagocytosis (CP) recovered to normal values, but the index of phagocytosis (IP) remained decreased. During and after chemotherapy, as well as one year after surgery, the IP still remained decreased. CONCLUSION: Our results showed that some properties of monocytes' phagocytic activity in cancer patients were decreased at diagnosis, returning back to normal range after surgical therapy. However, time is needed to confirm whether the alteration of IP may provide additional information when monitoring breast cancer patients. PMID- 17335141 TI - A negative adaptive response is expressed in peripheral blood lymphocytes that are exposed to mitomycin C and cycloheximide. AB - PURPOSE: Mitomycin C (MMC) and cycloheximide (CHX) are known for their apoptotic and antitumor activity. CHX is also known for its property to inhibit protein synthesis and to reduce cytotoxicity of various antitumor drugs, i.e. inducing an adaptive survival response (ASR). The purpose of this study was to evaluate the effect of ASR induced by CHX in cells exposed to clastogenic doses of MMC. MATERIALS AND METHODS: In all experiments we used human peripheral blood lymphocytes of 10 healthy male non-smokers, 25-35 years of age. Three groups were established. One control group of PBS-treated group. Two distinctive experimental groups were based on the induction or non-induction of ASR by CHX, i.e. one with MMC alone and a second one with CHX and MMC. The effect of ASR was induced by CHX at a dose of 10 mug/ml. MMC was used in 3 dose levels: 0.05 muM, 0.15 muM and 0.6 muM. To evaluate ASR induced by CHX in cells exposed to MMC we used the cytokinesis-blocked micronucleus test (CBMN) in vitro. RESULTS: CHX at a dose of 10 mg/ml induced an ASR in human peripheral blood lymphocytes of healthy subjects exposed to increasing doses of MMC. CHX induced statistically highly significant difference (p < 0.001) in the nuclear division index (NDI) compared to cells exposed to MMC alone. Genotoxicity of MMC measured by the percentage of micronuclei in binuclear (BN) cells was not elevated in the presence of CHX. Also, the increase in the NDI was correlated with the decrease in nuclear fragmentation (NF). CONCLUSION: The observed differences in NF and the NDI between the two groups showed that ASR to MMC induced by CHX could be a consequence of inhibition of apoptosis. We argue that adaptation (pro-life processes) can overwhelm its positive aspects (antimutagenic and anticarcinogenic) by increasing the population of cells with chromosome aberrations (chromosome instability) by apoptotic inhibition. CHX disturbs the apoptotic signal. Understanding that ASR can act as a pro-survival process leading to inhibition of apoptosis shall enhance in the future our knowledge of anticarcinogenesis, thus utilizing new paths for better treatment of cancer. PMID- 17335142 TI - Early postoperative glutamine-supplemented parenteral nutrition versus enteral immunonutrition in cancer patients undergoing major gastrointestinal surgery. AB - PURPOSE: The aim of this study was to determine whether the type of postoperative feeding, glutamine-supplemented parenteral nutrition or enteral immunonutrition, can modify morbidity and outcome in malnourished cancer patients undergoing major surgery in the gastrointestinal tract. PATIENTS AND METHODS: Twenty-nine consecutive malnourished patients undergoing major elective surgery for carcinoma of the stomach (n=8), pancreas (n=8), liver (n=1), and colon (n=12), were randomly assigned to receive from the first postoperative day either enteral immunonutrition or glutamine-supplemented parenteral nutrition, for at least 5 consecutive days. Postoperative major and minor morbidity and mortality were recorded. Data analysis was done using the Fisher's exact test. RESULTS: Fifteen patients received glutamine-supplemented parenteral nutrition and 14 received enteral immunonutrition. The overall incidence of postoperative complications was 33.3% in the parenteral nutrition group versus 50% in the enteral nutrition group (p=0.2). Subdividing postoperative complications into different types, the rates of major complications were similar in both groups of patients (13.3 and 21.4% respectively, p=0.4). Similarly, there were no significant differences between the two groups considering minor postoperative noninfectious complications, infectious complications, and mortality. CONCLUSION: In malnourished cancer patients undergoing major gastrointestinal surgery, morbidity and mortality are not significantly influenced by the type of postoperative feeding. PMID- 17335143 TI - Fluoroscopy and Paget's disease of the breast. AB - A case report concerning a 36-year-old woman having developed Paget's disease of the breast subsequent to multiple fluoroscopies as a child for the investigation of Fallot's anomaly/pulmonary atresia is presented. This case is discussed with a brief review of the relevant literature regarding current theories as to the pathogenesis of Paget's disease of the breast, ionizing radiation and its role in dysplastic breast disease and their possible interrelation. PMID- 17335144 TI - Localized hyaline plaque of the diaphragmatic peritoneum: report of a rare entity mimicking a hepatic tumor. AB - A liver tumor (2.5x3 cm) with malignant features on computed tomography (CT) and magnetic resonance imaging (MRI) was detected in a 69-year-old man with hepatitis B virus (HBV)-associated cirrhosis. On exploratory laparotomy a mass at the right diaphragmatic dome adherent to the liver segment VIII was found. En-block resection of this segment and the part at diaphragm hosting the tumor was carried out. On histology the tumor was a diaphragmatic hyaline plaque while in the resected liver no tumor was found. PMID- 17335146 TI - Carcinoma of the prostate. A historical account. AB - With this paper the author presents some historical notes concerning prostatic cancer. He analyses the first recorded carcinomas of the prostate, its surgical treatment, radiotherapy, hormonotherapy and the diagnostic procedures. PMID- 17335145 TI - Melanosis coli in two patients with colorectal neoplasia. AB - Melanosis coli is characterized by pigment deposition in the lamina propria and caused by increased epithelial apoptosis. Chronic laxative use induces melanosis coli and possibly increases colorectal cancer risk. We report on two cases of melanosis coli, one with colorectal carcinoma and the other with adenoma. PMID- 17335147 TI - Could chekhovian humanism help us today? PMID- 17335149 TI - Making sense of diagnostic test likelihood ratios. PMID- 17335148 TI - Identification of XAGE-1 isoforms: predominant expression of XAGE-1b in testis and tumors. AB - XAGE-1 is a cancer/testis (CT) antigen and has been shown to be immunogenic in lung cancer patients. Among 4 alternative splicing variants, XAGE-1a, b, c and d, XAGE-1b mRNA was dominantly expressed in cancer. In this study, we generated a XAGE-1b mAb, USO9-13. The B cell epitope recognized by the USO9-13 mAb was in the C-terminal region of the XAGE-1b protein and is also recognized by sera from patients with lung adenocarcinoma. Using USO9-13 and an anti-Flag mAb, we examined the translation products of the 4 transcripts. The XAGE-1a and b transcripts translated to the XAGE-1b protein. The XAGE-1c transcript possibly translated to 9- and 17-aa polypeptides. The XAGE-1d transcript translated to a protein consisting of 69 amino acids. Immunofluorescence analysis using USO9-13 mAb showed that the XAGE-1b protein is located in the nuclei of cells. Immunohistochemically, nuclear staining was heterogeneously observed in 25/47 lung adenocarcinomas, 1/12 hepatocellular carcinomas and 1/11 gastric cancers, but not in adjacent normal tissues. These findings suggested that XAGE-1b is a promising target molecule for a cancer vaccine against lung cancer. PMID- 17335150 TI - Simplified calculations using likelihood ratios. PMID- 17335151 TI - Misunderstandings, misperceptions, and mistakes. PMID- 17335152 TI - An abnormal D-dimer test result indicated that anticoagulation should be continued. PMID- 17335153 TI - Atorvastatin at 80 mg/d reduced cerebrovascular events more than did atorvastatin at 10 mg/d in stable coronary heart disease. PMID- 17335154 TI - Adjuvant vinorelbine plus cisplatin extended survival longer than observation in resected non-small-cell lung cancer. PMID- 17335155 TI - Stenting led to more stroke or death than did endarterectomy in symptomatic carotid stenosis >/= 60%. PMID- 17335156 TI - Noninferiority was not shown between stenting and endarterectomy in severe symptomatic carotid stenosis. PMID- 17335157 TI - Community-based occupational therapy improved daily functioning in older patients with dementia. PMID- 17335158 TI - Olanzapine, quetiapine, or risperidone did not differ from placebo for Alzheimer disease. PMID- 17335159 TI - Review: trials of injectable pneumococcal vaccines do not show effectiveness in chronic obstructive pulmonary disease. PMID- 17335160 TI - A lifestyle intervention continued to prevent type 2 diabetes in high-risk patients after the program was stopped. PMID- 17335161 TI - Review: inhaled insulin provides better glycemic control than oral hypoglycemic agents but not better than subcutaneous insulin. PMID- 17335162 TI - Sitagliptin improved glycemic control and beta-cell function in type 2 diabetes. PMID- 17335164 TI - Physical counterpressure maneuvers reduced vasovagal syncope. PMID- 17335163 TI - Review: pioglitazone does not reduce risk for mortality or cardiovascular events in type 2 diabetes. PMID- 17335165 TI - Review: success of lumbar puncture is enhanced by reinserting the stylet before removing the needle. PMID- 17335166 TI - Ultrasonographic guidance increased successful insertion of internal jugular vein catheter in the emergency department. PMID- 17335167 TI - Etoricoxib was noninferior to diclofenac for cardiovascular outcomes in osteoarthritis and rheumatoid arthritis. PMID- 17335168 TI - Microscopic-observation drug-susceptibility assay was more sensitive than standard tests for diagnosing tuberculosis. PMID- 17335169 TI - Persistent right ventricular dysfunction increased risk for recurrent venous thromboembolism after acute pulmonary embolism. PMID- 17335170 TI - Discontinuation of medications 1 month after an acute myocardial infarction increased risk for death at 12 months. PMID- 17335171 TI - Review: high alcohol intake increases mortality in both men and women. PMID- 17335172 TI - Urgent revascularization with PCI was more cost-effective than CABG in medically refractory, high-risk myocardial ischemia. PMID- 17335173 TI - Simvastatin was cost-effective across a broad range of risk and age groups. PMID- 17335174 TI - A simple risk score discriminated between patients at low or high risk for adverse events during therapy for acute DVT. PMID- 17335175 TI - A risk model predicted major bleeding in older patients with atrial fibrillation receiving warfarin therapy. PMID- 17335176 TI - The MMRpro model accurately predicted the probability of carrying a cancer susceptibility gene mutation for the Lynch syndrome. PMID- 17335177 TI - Synthesis of symmetrical and unsymmetrical PAMAM dendrimers by fusion between azide- and alkyne-functionalized PAMAM dendrons. AB - A new convergent synthetic method for the synthesis of PAMAM dendrimers has been developed. The fusion between propargyl-functionalized PAMAM dendrons and azido functionalized PAMAM dendrons via the Cu(I)-catalyzed Huisgen [2 + 3] dipolar cycloaddition reaction (click chemistry) of an alkyne and an azide leads to the formation of symmetric PAMAM dendrimers in high yields. Furthermore, the coupling reactions between the different generation dendrons afford the size differentiated unsymmetrical PAMAM dendrimers. PMID- 17335179 TI - Charge-remote metastable ion decomposition of free fatty acids under FAB MS: evidence for biradical ion structures. AB - Classical charge-remote fragmentation (CRF) of a series of long-chain saturated and monounsaturated fatty acid anions, a well-known phenomenon under collisional activation conditions, is observed for the first time during fast atom bombardment of the analyte-matrix mixture without collisional activation. The process is efficient enough to allow collision-induced dissociation and metastable ion decomposition MS/MS spectra of any charge-remote [M-H2-(CH2)n]- fragments as well as spectra of neutral losses to be recorded. The results obtained are in contradiction to the generally accepted theory that CRF results exclusively in terminally unsaturated carboxylate anions. The new results indicate that a multistep radical mechanism is involved in CRF ion formation. The first step of the process appears to be accompanied by hydrogen elimination that occurs randomly throughout the molecule. The primary fragment radical ions formed can decompose further with the formation of the next generation of CRF ions. PMID- 17335180 TI - Halo ion trap mass spectrometer. AB - We describe a novel radio frequency ion trap mass analyzer based on toroidal trapping geometry and microfabrication technology. The device, called the halo ion trap, consists of two parallel ceramic plates, the facing surfaces of which are imprinted with sets of concentric ring electrodes. Radii of the imprinted rings range from 5 to 12 mm, and the spacing between the plates is 4 mm. Unlike conventional ion traps, in which hyperbolic metal electrodes establish equipotential boundary conditions, electric fields in the halo ion trap are established by applying different radio frequency potentials to each ring. The potential on each ring can be independently optimized to provide the best trapping field. The halo ion trap features an open structure, allowing easy access for in situ ionization. The toroidal geometry provides a large trapping and analyzing volume, increasing the number of ions that can be stored and reducing the effects of space-charge on mass analysis. Preliminary mass spectra show resolution (m/Deltam) of 60-75 when the trap is operated at 1.9 MHz and 500 Vp-p. PMID- 17335181 TI - Spin coherence transfer in chemical transformations monitored by remote detection NMR. AB - We demonstrate a nuclear magnetic resonance (NMR) experiment using continuous flow in a microfluidic channel for studying the transfer of spin coherence in nonequilibrium chemical processes. We use the principle of remote detection, which involves spatially separated NMR encoding and detection coils. As an example, we provide the map of chemical shift correlations for the amino acid alanine as it transitions from the zwitterionic to the anionic form. The presented method uniquely allows for tracking the migration of encoded spins during the course of any chemical transformation and can provide useful information about reaction mechanisms. PMID- 17335182 TI - Gas-phase pyridylamination of saccharides: development and applications. AB - Pyridylamination is a versatile method for fluorescence labeling of oligosaccharides. The technique affords sensitive detection of saccharides with reducing termini and high-resolution separation by high-performance liquid chromatography. The conventional method, based on a liquid-phase reaction, has been extensively used in various aspects of glycobiology and glycotechnology. Unfortunately, the necessity for removing excess 2-aminopyridine makes the technique both laborious and time-consuming. Furthermore, removal of excess reagent can result in a significant loss of short saccharide components. In the present paper, we report an alternative methodology based on a "gas-phase" reaction, in which dried saccharides are reacted with vaporized 2-aminopyridine. The resultant Schiff base was also reduced in the gas phase within the same reaction microtube using a purpose-built device. The newly developed procedure was applied to both monosaccharide (GlcNAc) and oligosaccharides (isomalto oligosaccharides) at quantitative yields with no requirement to remove excess reagent. The acid-labile sialyl linkages of alpha2-6-disialobiantennary oligosaccharides proved to be fully stable during the procedure. The developed method was also successfully applied to profiling N-linked oligosaccharides liberated from glycoproteins by hydrazinolysis and, thus, should contribute to various fields of glycomics. PMID- 17335183 TI - Inhibition of secreted phospholipase A2. 4-glycerol derivatives of 4,5-dihydro-3 (4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one with broad activities. AB - Secreted phospholipases A2 (sPLA2s) have been reported to play an important role in various inflammatory conditions and thus represent an attractive therapeutic target. Previous SAR studies from our laboratory have revealed certain important features of our recently discovered specific hGIIA sPLA2 inhibitors, and we report here the synthesis and biological activities of glycerol-containing derivatives of our lead compound III (Figure 1). Efficient and selective synthesis methods have been developed to make glycerol trisubstituted by different groups on desired positions. In terms of biological activities, the best compounds (A3, A6, and A15) are more active than III (Figure 1), as potent as Me-Indoxam, an sPLA2s inhibitor of reference, against hGIIA, hGV, and hGX sPLA2s and at least 10 times less active toward the GIB enzymes in two in vitro assay systems. By synthesis of enantiopure (S)-A6, we demonstrated that no important improvement of the inhibitory potency could be achieved by this approach. Furthermore, the results show that the global lipophilicity is likely responsible for the anti-PLA2 activity and two oxadiazolone moieties seem too big to be accommodated by the active site of the hGIIA enzyme. PMID- 17335184 TI - NO-donor COX-2 inhibitors. New nitrooxy-substituted 1,5-diarylimidazoles endowed with COX-2 inhibitory and vasodilator properties. AB - A series of NO-donor diarylimidazoles derived from the lead compound Cimicoxib were synthesized and evaluated for their COX-2 inhibitory activity and their stability in whole blood as well as for vasodilator properties. The products are partly transformed into the corresponding alcohols following 24-h incubation in whole blood. All of them display good COX-1/COX-2 selectivity, but are less potent than the lead; a molecular modeling study was carried out to investigate their binding mode. The compounds are also capable of relaxing rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism; this property could confer reduced cardiotoxicity with respect to traditional COX-2 inhibitors. PMID- 17335185 TI - Novel N-substituted indol-3-ylglyoxylamides probing the LDi and L1/L2 lipophilic regions of the benzodiazepine receptor site in search for subtype-selective ligands. AB - Novel N-substituted indol-3-ylglyoxylamides (10-37) were synthesized and evaluated as ligands of the benzodiazepine receptor (BzR). In an effort to achieve affinity-based selectivity among BzR subtypes, these compounds were designed to probe the LDi and L2 lipophilic regions. Taking the alpha1-selective benzylindolylglyoxylamides Ia and Ib as leads, we varied the substituent on the benzylamide phenyl ring (compounds 10-23) or replaced the benzyl moiety with alkyl groups (compounds 24-37). The above structural changes gave no shift of selectivity from the alpha1 toward the alpha2 or alpha5 subtypes, thus confirming that a ligand which occupies the LDi region probably exhibits alpha1 selectivity, despite its interactions with other lipophilic areas in the receptor binding cleft. Compound 11 (N-(p-methylbenzyl)-5-nitroindol-3-ylglyoxylamide), which selectively binds with a full agonist efficacy at the alpha1 receptor subtype and displays sedative action, can be regarded as an interesting potential zolpidem like sedative-hypnotic agent. PMID- 17335186 TI - Characterizing the 1,4-dihydropyridines binding interactions in the L-type Ca2+ channel: model construction and docking calculations. AB - L-type Ca2+ channels (LCC) are membrane heteromultimeric proteins that allow the selective entrance of Ca2+ ions into excitable cells upon membrane depolarization. Despite the large amount of compounds (1,4-dihydropyridines, phenylalkylamines, and benzothiazepines) that impede the passage of Ca2+ ions through the channel, it is still not clear how these molecules bind to LCC at an atomic level. In this study, a 3D model of the central pore of LCC was constructed using the X-ray structure of the KcsA K+ channel as template. The resulting LCC model was then used to dock nine different DHPs to shed light on their binding mode. The accordance between the developed model and several experimental data gives us the confidence to propose our model as a valuable platform for future studies aimed at the identification of new potent and LCC selective ligands. PMID- 17335187 TI - Enzymatically activated cycloSal-d4T-monophosphates: The third generation of cycloSal-pronucleotides. AB - The third generation of cycloSal-pronucleotides, 5-diacetoxymethyl-cycloSal-d4T monophosphates (5-di-AM-cycloSal-d4TMPs), is reported as a new class of "lock-in" modified cycloSal-pronucleotides. These compounds bear an esterase-cleavable geminal dicarboxylate (acylal) attached to the aromatic ring of the saligenyl unit. The conversion into a strong acceptor group (aldehyde) leads to a strong decrease in hydrolytic stability. As a consequence, a fast release of a nucleoside monophosphate (i.e., d4TMP) follows. The concept of this enzymatic activation is proven by hydrolysis studies in phosphate buffer, cell extracts, and human serum. These investigations showed the conversion of the acylal group into a polar aldehyde by enzymatic cleavage. Besides, antiviral activities against HIV are presented. PMID- 17335188 TI - Stressin1-A, a potent corticotropin releasing factor receptor 1 (CRF1)-selective peptide agonist. AB - The potencies and selectivity of peptide CRF antagonists is increased through structural constraints, suggesting that the resulting ligands assume distinct conformations when interacting with CRF1 and CRF2 receptors. To develop selective CRF receptor agonists, we have scanned the sequence -Gln-Ala-His-Ser-Asn-Arg- (residues 30-35 of [DPhe12,Nle21,38]Ac-hCRF4-41) with an i-(i+3) bridge consisting of the Glui-Xaa-Xbb-Lysi+3 scaffold, where residues i=30, 31, and 32. When i=31, stressin1-A, a potent CRF1 receptor-selective agonist was generated. In vitro, stressin1-A was equipotent to h/rCRF to release ACTH. Astressin1-A showed a low nanomolar affinity for CRF1 receptor (Ki=1.7 nM) and greater than 100-fold selectivity versus CRF2 receptor (Ki=222 nM). Stressin1-A released slightly less ACTH than oCRF in adult adrenal-intact male rats, with increased duration of action. Stressin1-A, injected intraperitoneally in rats, induced fecal pellet output (a CRF1 receptor-mediated response) and did not influence gastric emptying and blood pressure (CRF2 receptor-mediated responses). PMID- 17335189 TI - Design, synthesis, and evaluation of the antiproliferative activity of a series of novel fused xanthenone aminoderivatives in human breast cancer cells. AB - Derivatives of two novel, structurally related heterocyclic ring systems, xantheno[3,4-d]imidazole and chromeno[4,3,2-c,d]imidazo[4,5-f]indazole, bearing aminoalkyl side chains, have been synthesized, and their antiproliferative activity has been studied against the aggressive human breast MDA-MB-231 cell line. The pyrazole-fused analogue 27a possesses a pronounced antiproliferative effect on the tested cell line, evident at 1 muM, and achieves an IC50 of 6.5 microM. PMID- 17335190 TI - N-(3,3a,4,4a,5,5a,6,6a-Octahydro-1,3-dioxo-4,6- ethenocycloprop[f]isoindol-2-(1H) yl)carboxamides: Identification of novel orthopoxvirus egress inhibitors. AB - A series of novel, potent orthopoxvirus egress inhibitors was identified during high-throughput screening of the ViroPharma small molecule collection. Using structure--activity relationship information inferred from early hits, several compounds were synthesized, and compound 14 was identified as a potent, orally bioavailable first-in-class inhibitor of orthopoxvirus egress from infected cells. Compound 14 has shown comparable efficaciousness in three murine orthopoxvirus models and has entered Phase I clinical trials. PMID- 17335205 TI - Sequential silylcarbocyclization/silicon-based cross-coupling reactions. AB - A sequential rhodium-catalyzed silylcarbocyclization of enynes parlayed with a palladium-catalyzed, silicon-based cross-coupling reaction has been developed for the synthesis of highly substituted cyclopentanes. 1,6-Enynes reacted with benzyldimethylsilane in the presence of rhodium catalysts to afford five-membered rings bearing a (Z)-alkylidenylbenzylsilyl group. A variety of substitution patterns and heteroatom substituents were compatible. The silylcarbocyclization in which an unsaturated ester participated was also achieved. The resulting alkylidenylsilanes underwent palladium-catalyzed cross-coupling using tetra-n butylammonium fluoride. This cross-coupling reaction displayed a broad substrate scope. A wide variety of substitution patterns, electronic properties, and heteroatoms were compatible. All of the cross-coupling reactions proceeded in high yields under very mild conditions and with complete retention of double bond configuration, resulting in densely functionalized 3-(Z)-benzylidenecyclopentanes and heterocycles. PMID- 17335206 TI - Effect of elemental composition of PtPd bimetallic nanoparticles containing an average of 180 atoms on the kinetics of the electrochemical oxygen reduction reaction. AB - PtPd bimetallic nanoparticles containing an average of 180 atoms and composed of seven different Pt:Pd ratios have been prepared within sixth-generation, hydroxyl terminated, poly(amidoamine) dendrimers. Transmission electron microscopy indicates that the sizes of all seven nanoparticle compositions are within +/-0.2 nm of one another and the calculated size. Single-particle energy-dispersive spectroscopy shows that the elemental composition is determined by the ratio of the Pt and Pd precursor salts used to prepare the nanoparticles. Cyclic voltammetry and rotating disk voltammetry measurements show that the Pt:Pd ratio of the nanoparticles determines their efficiency for the oxygen reduction reaction (ORR). The maximum activity for the ORR occurs at a Pt:Pd ratio of 5:1, which corresponds to a relative mass activity enhancement of 2.4 compared to otherwise identical monometallic Pt nanoparticles. PMID- 17335207 TI - Protein flexibility and species specificity in structure-based drug discovery: dihydrofolate reductase as a test system. AB - In structure-based drug discovery, researchers would like to identify all possible scaffolds for a given target. However, techniques that push the boundaries of chemical space could lead to many false positives or inhibitors that lack specificity for the target. Is it possible to broadly identify the appropriate chemical space for the inhibitors and yet maintain target specificity? To address this question, we have turned to dihydrofolate reductase (DHFR), a well-studied metabolic enzyme of pharmacological relevance. We have extended our multiple protein structure (MPS) method for receptor-based pharmacophore models to use multiple X-ray crystallographic structures. Models were created for DHFR from human and Pneumocystis carinii. These models incorporate a fair degree of protein flexibility and are highly selective for known DHFR inhibitors over drug-like non-inhibitors. Despite sharing a highly conserved active site, the pharmacophore models reflect subtle differences between the human and P. carinii forms, which identify species-specific, high affinity inhibitors. We also use structures of DHFR from Candida albicans as a counter example. The available crystal structures show little flexibility, and the resulting models give poorer performance in identifying species-specific inhibitors. Therapeutic success for this system may depend on achieving species specificity between the related human host and these key fungal targets. The MPS technique is a promising advance for structure-based drug discovery for DHFR and other proteins of biomedical interest. PMID- 17335208 TI - Design of an emission ratiometric biosensor from MerR family proteins: a sensitive and selective sensor for Hg2+. PMID- 17335209 TI - Reversibly photoswitchable dual-color fluorescent nanoparticles as new tools for live-cell imaging. PMID- 17335210 TI - Highly enantiomeric supramolecular [4 + 4] photocyclodimerization of 2 anthracenecarboxylate mediated by human serum albumin. PMID- 17335211 TI - Synthesis and mechanistic study of palladium nanobars and nanorods. AB - This paper describes a simple and versatile method for growing highly anisotropic nanostructures of Pd, single-crystal nanobars bounded by {100} facets and single crystal nanorods with their side surfaces enclosed by {100} and {110} facets. According to thermodynamic arguments, Pd atoms should nucleate and grow in a solution phase to form cuboctahedrons of spherical shape with their surfaces bounded by a mix of {111} and {100} facets. Anisotropic nanostructures can only form under kinetically controlled conditions, while the cubic symmetry is broken. In the present system, we found that one-dimensional growth could be induced and maintained through an interplay of the following processes: (i) speedy reduction of the precursor to ensure prompt addition of atoms to the seed; (ii) chemisorption of bromide on the seed to promote the formation of {100} and {110} facets; and (iii) localized oxidative etching on one specific face of the seed to initiate preferential growth on this face. Experimentally, the anisotropic growth can be achieved by varying the type and concentration of reducing agent, as well as by adjusting the reaction temperature. This methodology developed for Pd has also been extended to both Au and Pt. As expected for a kinetically controlled product, the anisotropic nanostructure evolved into the thermodynamically favored shape during an aging process. PMID- 17335212 TI - Variation of linker length in ratiometric fluorescent sensor proteins allows rational tuning of Zn(II) affinity in the picomolar to femtomolar range. PMID- 17335213 TI - The total synthesis of spirotenuipesines A and B. PMID- 17335214 TI - Characterization and mechanism of formation of tandem lesions in DNA by a nucleobase peroxyl radical. AB - 5,6-Dihydro-2'-deoxyuridin-6-yl (1) was independently generated via photolysis of 3. The radical is an analogue of the major reactive species produced from thymidine upon reaction with hydroxyl radical, which is the dominant DNA-damaging agent produced by the indirect effect of gamma-radiolysis. Under aerobic conditions, the peroxyl radical (2) derived from 1 reacts approximately 82% of the time with either the 5'- or 3'-adjacent nucleotide to produce two contiguously damaged nucleotides, known as tandem lesions. The structures and distribution of tandem lesions were investigated using probes that selectively detect abasic sites, ESI-MS/MS, and competition kinetics. In addition to 2 deoxyribonolactone, nonoxidized abasic sites were detected. 18O-Labeling verified that H2O was the source of oxygen in the abasic sites, but that O2 was the source of the oxygen in the 5,6-dihydro-6-hydroxy-2'-deoxyuridine derived from 2. ESI MS/MS experiments, in conjunction with isotopic labeling, identified several products and provided direct evidence for peroxyl radical addition to the adjacent thymine bases. Kinetic studies revealed that peroxyl radical addition to the 5'-thymine was favored by approximately 4-5-fold over C1'-hydrogen atom abstraction from the respective deoxyribose ring, and that 2-deoxyribonolactone formation accounts for approximately 11% of the total amount of tandem lesions produced. These results suggest that tandem lesions, whose biochemical effects are largely unknown, constitute a major family of DNA damage products produced by the indirect effect of gamma-radiolysis. PMID- 17335217 TI - Palladium-catalyzed methylation and arylation of sp2 and sp3 C-H bonds in simple carboxylic acids. PMID- 17335216 TI - Antibody-catalyzed oxidation of delta(9)-tetrahydrocannabinol. AB - Marijuana abuse continues to plague society and the lack of effective treatments warrants concern. Catalytic antibodies capable of oxidatively degrading the major psychoactive component of marijuana, Delta9-tetrahydrocannabinol (Delta9-THC), are presented. The antibodies generate reactive oxygen species from singlet oxygen (1O2*), using riboflavin (vitamin B2) and visible light as the 1O2* source. Cannabitriol was identified as the major degradation product of this reaction, demonstrating the ability of an antibody to catalyze a complex chemical transformation with therapeutic implications for treating marijuana abuse. PMID- 17335218 TI - Enantioselective, cyclopentene-forming annulations via NHC-catalyzed benzoin-oxy cope reactions. PMID- 17335219 TI - Porosity and its effect on the digestibility of dilute sulfuric acid pretreated corn stover. AB - Enzyme accessibility has been proposed as a limiting factor in the enzymatic conversion of the cellulose in biomass to glucose. Prior work has shown a strong correlation between porosity, measured as the change in the volume of pores accessible to a cellulase-sized molecule, and the initial digestibility of biomass pretreated by various methods. The goal of this work was to determine if porosity was one of the factors governing the overall enzymatic digestibility of the cellulose in dilute acid pretreated biomass. The porosity of wet pretreated corn stover was determined using the methods of solute exclusion and 1H nuclear magnetic resonance (NMR) thermoporometry. The solute exclusion method identified differences in the accessible pore volume of the pretreated samples compared to untreated corn stover; however, only very small differences in porosity were observed among samples pretreated with a range of severities, giving ethanol yields from 70 to 96%. No correlation was found between the volume accessible to an enzyme-sized molecule (diameter estimated to be 51 A) and the digestibility of the cellulose in dilute acid pretreated corn stover. 1H NMR thermoporometry was used to measure the amount of water in pores ranging from 20 to 200 A. As was the case for the solute exclusion method, a difference was observed in the pore volume of untreated and acid pretreated corn stover, but no significant differences in pore volume were measured for the different pretreated samples. PMID- 17335220 TI - Alaska pink salmon (Oncorhynchus gorbuscha) spoilage and ethanol incidence in the canned product. AB - Ethanol was quantified in canned salmon produced from whole fish showing different stages of decomposition due to storage at 1 and 14 degrees C for up to 3 and 16 days, respectively. Ethanol incidence in the canned salmon was correlated to results from skin aerobic plate counts and sensory evaluations of the whole fish and with sensory evaluations of the canned product. Panelists rejected whole salmon after 3 and 12 days of storage at 14 and 1 degrees C, respectively. Skin aerobic plate counts reached 4.8 log CFU/cm2 when fish were rejected, regardless of storage temperature. Panelists rejected canned salmon produced with fish stored for a maximum of 2 and 16 days at 14 and 1 degrees C, respectively. Ethanol concentrations in the cans produced with fish stored at 14 degrees C correlated well with sensory evaluation results; however, ethanol concentrations in the cans produced with salmon stored at 1 degrees C did not agree with sensory results. A correlation could not be established between ethanol concentration in the canned product and microbial content of whole salmon. PMID- 17335221 TI - Characterization of carotenoid pigments in mature and developing kernels of selected yellow-endosperm sorghum varieties. AB - Sorghum is a critical source of food in the semiarid regions of sub-Saharan Africa and India and a potential source of dietary phytochemicals including carotenoids. The objective of this study was to determine the carotenoid profiles of sorghum cultivars, selected on the basis of their yellow-endosperm kernels, at various developmental stages. Following extraction from sorghum flours, carotenoids were separated by high-performance liquid chromatography (HPLC) with diode array detection. Total carotenoid content in fully matured yellow-endosperm sorghum kernels (0.112-0.315 mg/kg) was significantly lower (p < 0.05) than that in yellow maize (1.152 mg/kg) at physiological maturity. Variation in total carotenoids and within individual carotenoid species was observed in fully mature sorghum cultivars. For developing kernels, large increases in carotenoid content occurred between 10 and 30 days after half bloom (DAHB), resulting in a peak accumulation between 6.06 and 28.53 microg of total carotenoids per thousand kernels (TK). A significant (p < 0.05) decline was noted from 30 to 50 DAHB, resulting in a final carotenoid content of 2.62-15.02 microg/TK total carotenoids. (all-E)-Zeaxanthin was the most abundant carotenoid, ranging from 2.22 to 13.29 microg/TK at 30 DAHB. (all-E)-Beta-carotene was present in modest amounts (0.15-3.83 microg/TK). These data suggest the presence of genetic variation among sorghum cultivars for carotenoid accumulation in developing and mature kernels. PMID- 17335222 TI - Pathway analysis of branched-chain ester biosynthesis in apple using deuterium labeling and enantioselective gas chromatography-mass spectrometry. AB - The biosynthesis of volatile esters by Red Delicious apples was investigated by incubating fruit tissue with deuterated flavor precursors at various times after controlled atmosphere (CA) storage and measuring deuterium incorporation into branched-chain ester volatiles. 2-Methylbutyl acetate was the only volatile not significantly reduced by CA storage. Conversion of 2-methylbutanol to 2 methylbutyl acetate and of 2-methylbutanoic acid to ethyl 2-methylbutanoate and to hexyl 2-methylbutanoate was limited by the availability of 2-methylbutyl substrates but not by acetyl-CoA, ethanol, or hexanol, respectively. The enzymatic activity required for these reactions declined during CA storage. The conversion of 2-methylbutanoic acid to 2-methylbutanol was also substrate limited, but enzymic activity appeared stable in storage. Biosynthesis of both 2 methylbutanoic acid and 2-methylbutanol, from isoleucine, was severely depressed under CA storage. The reduced metabolism of isoleucine to 2-methylbutanoyl-CoA may be the primary reason for reduced branched-chain ester synthesis in CA-stored Red Delicious apples. Enantioselective gas chromatography-mass spectrometry confirmed that the chirality of (S)-2-methylbutyl acetate derives from l isoleucine with the other enzymes in this pathway not being enantiospecific. Treatment of tissue samples with 2-methylbut-2E-enal gave only (S)-2-methylbutyl acetate, indicating that biosynthesis was not via tiglyl-CoA. PMID- 17335223 TI - Specificity analysis of anti-gliadin mouse monoclonal antibodies used for detection of gliadin in food for gluten-free diet. AB - A gluten-free diet (GFD) is the sole effective long-lasting treatment of celiac disease. Four monoclonal antibodies (Abs) were prepared by immunization of animals kept on GFD with gliadin. The specificity of these Abs to decapeptides of alpha- and gamma-gliadin and omega-secalin was analyzed by the PEPSCAN technique. Repetitive sequences of alpha- and gamma-gliadin and omega-secalin containing the motifs QPFPXQ (X = Q, L, P) were recognized by all Abs tested. These Abs also frequently reacted with peptides containing the sequences QQSFPQQ, QQTFPQP, and QPFRPQ. On the basis of PEPSCAN results two Abs--8D4 and 7C6--were selected for the construction of a new ELISA kit for the detection of gliadin in food. The comparison of data obtained using the newly developed ELISA kit and commercially available ones indicated that Abs selection on the basis of their fine specificity to gliadin is useful for sensitive detection of gliadin in foods. PMID- 17335224 TI - Oxyresveratrol as an antibrowning agent for cloudy apple juices and fresh-cut apples. AB - Antibrowning activities of Morus alba L. twig extracts, oxyresveratrol, and mulberroside A isolated from mulberry twig on cloudy apple juices and fresh-cut apple slices were evaluated by monitoring the change of a* value, total color difference (DeltaE), and visual observation. It was found, similar to 4 hexylresorcinol, that oxyresveratrol could effectively inhibit browning in cloudy apple juices at a concentration as low as 0.01% and that mulberry twig extract also showed remarkable antibrowning effects on cloudy apple juices. However, for fresh-cut apple slices, mulberry twig extract and oxyresveratrol needed to be used in combination at least with ascorbic acid to exhibit their antibrowning effects. Apple slice samples treated by dipping in a solution containing 0.001 M oxyresveratrol, 0.5 M isoascorbic acid, 0.05 M calcium chloride, and 0.025 M acetylcysteine did not undergo any substantial browning reaction for 28 days at 4 degrees C. However mulberroside A did not show antibrowning effects on cloudy apple juices although it is also a good mushroom tyrosinase inhibitor. PMID- 17335225 TI - Lipoperoxidation and cyclooxygenases 1 and 2 inhibitory compounds from Iryanthera juruensis. AB - Plants from Iryanthera genus have been traditionally used as food supplements by South American Indians. The MeOH extract of leaves of Iryanthera juruensis, one of the plants endemic to the Amazon region and consumed in Brazil, and the hexane extract from its seeds inhibited lipid peroxidation (LPO) and cyclooxygenase (COX 1 and -2)) enzymes in in vitro assays. Further analyses of these extracts yielded 5-deoxyflavones (1-5) from the leaf extract and sargachromenol (6), sargaquinoic acid (7), a novel juruenolic acid (8), omega-arylalkanoic acids (9a-c), and the lignan guaiacin (10) from the seed extract. Compounds 3-5 inhibited LPO by 86%, 77%, and 88% at 10 ppm, respectively, and compounds 6 and 9a-c showed inhibition at 76% and 78% at 100 ppm, respectively. However, compounds 7 and 8 were inactive and lignan 10 exhibited LPO inhibitory activity by 99% at 100 ppm compared to commercial antioxidants butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and vitamin E. The flavones 1-5 also inhibited COX-1 and -2 enzymes by 50 65% at 100 ppm. Compound 6 showed high but nonselective inhibition of COX-1 and COX-2 enzymes, when compared to aspirin and Celebrex, a nonsteroidal anti inflammatory drug (NSAID). Compounds 7 and 10 inhibited COX-1 by 60% and 65% and COX-2 by 37% and 18%, respectively, whereas compounds 8 and 9a-c showed little or no activity against these enzymes. PMID- 17335226 TI - Highly stereoselective [4 + 3] cycloadditions of nitrogen-stabilized oxyallyl cations with pyrroles: an approach to parvineostemonine. AB - [structure: see text]. A highly stereoselective [4 + 3] cycloaddition of N substituted pyrroles with allenamide-derived nitrogen-stabilized chiral oxyallyl cations is described here. This method provides an approach for constructing tropinone alkaloids. PMID- 17335227 TI - An efficient and general approach to beta-functionalized ketones. AB - [structure: see text]. The oxidation of selected anions (N3-, SCN-, I-, and Br-) by ceric ammonium nitrate (CAN) in the presence of substituted cyclopropyl alcohols provides a novel approach to beta-functionalized ketones. The protocol has a number of advantages including short reaction times, ease of reagent handling, and mild, neutral reaction conditions. Overall, this method provides an alternative pathway to important starting materials and intermediates in organic synthesis. PMID- 17335228 TI - Efficient synthesis of fused perhydrofuro[2,3-b]pyrans (and furans) by ring opening of 1,2-cyclopropanated sugar derivatives. AB - [structure: see text]. An efficient method has been developed for the construction of fused perhydrofuro[2,3-b]pyrans by diastereoselective ring opening of 1,2-cyclopropanated sugar derivatives. The methodology has been successfully applied to the synthesis of fused perhydrofuro[2,3-b]pyrano-gamma butyrolactone derivatives. PMID- 17335229 TI - Highly efficient and stereoselective N-vinylation of oxiranecarboxamides and unprecedented 8-endo-epoxy-arene cyclization: expedient and biomimetic synthesis of some Clausena alkaloids. AB - [structure: see text]. Catalyzed by CuI/N,N-dimethylglycine, oxiranecarboxamides underwent a highly efficient and stereoselective N-vinylation reaction with (Z)-1 aryl-2-bromoethenes to afford the corresponding enamides. The method has been applied to a straightforward synthesis of (-)-(2R,3S)-SB204900, the enantiomer of the natural product. Following a hypothetic biomimetic pathway, both (+)-(5R,6S) xi-Clausenamide and (-)-(5R,6S)-balasubramide have been efficiently synthesized for the first time through the unprecedented intramolecular 8-endo-epoxy-arene cyclization of (Z)-N-(phenylvinyl)oxiranecarboxamides. PMID- 17335230 TI - Syntheses and applications of 2-phosphino-2'-alkoxy-1,1'-binaphthyl ligands. Development of a working model for asymmetric induction in hydrovinylation reactions. AB - Among the handful of monophosphine ligands that effect asymmetric hydrovinylation of vinylarenes, 2-diphenylphosphino-2'-methoxy-1,1'-binaphthyl (MOP) is among the most accessible. Addition of a methyl group at the 3'-position of this ligand significantly improves the enantioselectivity of hydrovinylation of prototypical alkenes. Introduction of a chiral phospholane at the C2 position of this scaffolding has no effect on the enantioselectivity. These results are consistent with a model proposed for the asymmetric induction for this exacting reaction. PMID- 17335231 TI - Cyclobutanones through SNi' ring closure, a mechanistic study. AB - Mechanistic studies on the intramolecular nucleophilic substitution with allylic rearrangement (SNi' reaction) and a new stereoselective access to substituted cyclobutanones are reported. 4,4-Dialkyl-5-oxohex-2E-en-1-yl methanesulfonates 4 were converted to 2,2-dialkyl-3-vinylcyclobutanones 6 by SNi' ring closure. The stereochemical analysis of the reaction was achieved through ring closure of (6S) 6-chloro-3,3-diethylhept-4E-en-2-one (S)-17, defined by the absolute configuration of C(6), leading to (3S)-2,2-diethyl-3-(prop-1E-en-1 yl)cyclobutanone (S)-(E)-18 and (3R)-2,2-diethyl-3-(prop-1Z-en-1-yl)cyclobutanone (R)-(Z)-18, in a ratio of 85:15, with almost complete transfer of chirality (>97%). The absolute configuration of (S)-17 was determined by X-ray diffraction analysis of the camphanoate derivative 16. The absolute configuration of the cyclobutanone products (S)-(E)-18 and (R)-(Z)-18 was determined by Raman optical activity spectroscopy. Comparison of the absolute configuration of (S)-17 and the resulting (E)- and (Z)-cyclobutanones 18 allowed the conclusion that the SNi' reaction proceeds with syn geometry relative to the leaving group. PMID- 17335232 TI - Generation of 3- and 5-lithiothiophene-2-carboxylates via metal-halogen exchange and their addition reactions to chalcogenoxanthones. AB - Deprotonation and lithium-bromine exchange in 5- or 3-bromothiophene-2-carboxylic acids with t-BuLi form the corresponding dianion, which reacts highly regioselectively in the presence of 0.25 equiv of tetramethyl-1,2-ethylenediamine with 3,6-bis(dimethylamino) chalcogenoxanthones to give S- and Se-containing rhodamines. Quenching studies with D2O indicate that an extra equivalent of t BuLi is not necessary in these reactions. Deprotonation is faster than metal halogen exchange with the bromothiophene-2-carboxylic acids using t-BuLi. PMID- 17335233 TI - Theoretical investigation of lone pair inversions, ring openings, and hydride shifts in O-methylated epoxides. AB - Mechanisms associated with the isomerization of the O-methylethylene oxonium ion and its tetramethyl-substituted analogue have been explored using correlated electronic structure calculations. The minima and transition states associated with inversion at the oxygen atom, as well as those associated with opening of the epoxide ring, have been characterized. The calculated barrier to inversion at the oxygen atom for the O-methylethylene oxonium ion, 15.7 kcal/mol, agrees well with the experimentally determined value, 10+/-2 kcal/mol. Our calculations indicate that a significantly higher barrier exists for the ring-opening mechanism that leads to more thermodynamically stable structures. This work includes the first known calculations on the O-methyl-2,3-dimethyl-2-butene oxonium ion along with transition states and intermediates associated with ring opening and inversion at the oxygen atom. Results show that there is a significantly lower barrier to ring opening as compared to the O-methylethylene oxonium ion species, leading to a lower probability of isolating this species. The effects of basis sets and correlation techniques on these ions were also analyzed in this work. Our results indicate that the B3LYP/6-31G* level is reliable for obtaining molecular geometries for both minima and transition states on the C3H7O+ and C7H15O+ potential energy surfaces. PMID- 17335234 TI - Electrosynthesis and characterization of 1,2-dibenzyl C60: a revisit. AB - A reinvestigation of the reaction between C60(2-) and benzyl bromide in benzonitrile containing 0.1 M tetra-n-butylammonium perchlorate (TBAP) has shown that there are more reaction products than previously reported. Use of a silica rather than a "Buckyclutcher I" column for HPLC purification led to isolation of two previously unattained products in the reaction mixture, one of which was identified as 1,2-(PhCH2)2C60 by UV-vis and NMR . The earlier incorrectly assigned 1,2-(PhCH2)2C60 was identified as the methanofullerene C61HPh by X-ray single-crystal diffraction. The electrochemistry of genuine 1,2-(PhCH2)2C60 shows that its first reduction potential in PhCN containing 0.1 M TBAP is cathodically shifted by 100 mV with respect to E1/2 for reduction of 1,4-(PhCH2)2C60, indicating that the addition pattern significantly affects the electrochemistry of derivatized C60. Visible and near-IR spectra of the monoanion and dianion of 1,2-(PhCH2)2C60 are also reported. PMID- 17335235 TI - Synthesis and conformational analysis of 17alpha,21-cyclo-22-unsaturated analogues of calcitriol. AB - Six new calcitriol analogues, conformationally restricted at their side chain by the introduction of both a cyclopropane ring at C17-C20 and a double or triple bond at C22, were synthesized using the Wittig-Horner approach to construct the triene system. The six CD-ring and side-chain bearing fragments were prepared from ketone 14 by a divergent route to generate both series of epimers at C20, followed by stereoselective cyclopropanation. The (E)-alkenyl side chain was synthesized by means of a Wittig reaction. The alkynyl side chain was prepared by Corey-Fuchs homologation, followed by alkylation. The (Z)-alkenyl side chain was prepared from the previous alkyne by partial hydrogenation. The 20-epi analogues bind more strongly to VDR than the corresponding analogues with the C20 natural stereochemistry. These results can be reasoned by conformational analysis and hydrophobic interactions with the VDR ligand-binding domain. PMID- 17335236 TI - Trifluoromethylation of alkenyl bromides and iodides (including 5-iodouracils) with (CF3)2Hg and Cu ("trifluoromethylcopper"). AB - Bromo- and iodoalkenes undergo trifluoromethylation efficiently in DMA with "CF3Cu" generated from (CF3)2Hg and Cu. Variable stereochemical inversion is observed with substrates having a gem-carbonyl group. Substrates having gem hydrogen, -alkyl, or -alkenyl groups give products with stereochemical retention. PMID- 17335237 TI - Control of the regioselectivity of sulfonamidyl radical cyclization by vinylic halogen substitution. AB - The radical cyclization reactions of unsaturated sulfonamides were investigated. The photolysis of N-(4-halo-4-pentenyl)sulfonamides (X=I, Br, or Cl) with (diacetoxyiodo)benzene (DIB) and iodine at room temperature afforded exclusively the corresponding piperidines in 73-98% yield via 6-endo radical cyclization. On the other hand, the reactions of N-(5-halo-4-pentenyl)sulfonamides with DIB/I2 led to the only formation of the pyrrolidine products in 84-99% yield via 5-exo radical cyclization. The vinylic halogen substitution not only successfully inhibits the competing ionic iodocyclization process to allow the radical cyclization to proceed smoothly but also shows a remarkable effect in controlling the regioselectivity of cyclization. PMID- 17335238 TI - On accounting for the stereoselective control of the metal-catalyzed Rautenstrauch cyclopropanation by computational methods. AB - The mechanism of the intramolecular Pt(II)-catalyzed Rautenstrauch cyclopropanation and the stereochemical implications have been investigated by computational methods. The reaction takes place through a cyclopropanation step preceding the cleavage of the C-O bond, thus ensuring the transfer of chiral information from the stereogenic propargylic center. Our results agree with experimental findings and account for the origin of the substrate-dependent selectivity on the basis of subtle electronic effects and steric interactions in the cyclopropanation transition-state structure. PMID- 17335239 TI - Mechanistic studies on the Heck-Mizoroki cross-coupling reaction of a hindered vinylboronate ester as a key approach to developing a highly stereoselective synthesis of a C1-C7 Z,Z,E-triene synthon for viridenomycin. AB - Mechanistic studies of the Heck-Mizoroki reaction of a vinylboronate ester with electronically different (four-substituted) aryl iodides shows that electron donors accelerate the cross-coupling, demonstrating that the oxidative addition step is not rate determining and that there is development of some degree of positive charge in the rate determining step. These results were used as a basis to allow the development of reaction conditions for the Heck-Mizoroki coupling of a hindered vinylboronate ester with electron deficient methyl cis-2-iodoacrylate. The resulting dienylboronate ester was converted through a series of highly stereoselective iodo-deboronations and Heck-Mizoroki reactions into a trienyl iodide precursor for further application in the total synthesis of viridenomycin. PMID- 17335240 TI - Regenerable chain-breaking 2,3-dihydrobenzo[b]selenophene-5-ol antioxidants. AB - A series of 2,3-dihydrobenzo[b]selenophene-5-ol antioxidants was prepared by subjecting suitably substituted allyl 4-methoxyphenyl selenides to microwave induced seleno-Claisen rearrangement/intramolecular Markovnikov hydroselenation followed by boron tribromide-induced O-demethylation. The novel antioxidants were assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system containing N-acetylcysteine as a thiol reducing agent in the aqueous phase. Antioxidant efficiency as determined by the inhibited rate of peroxidation, Rinh, increased with increasing methyl substitution (Rinh=46-26 microM/h), but none of the compounds could match alpha tocopherol (Rinh=22 microM/h). Regenerability as determined by the inhibition time, Tinh, in the presence of the thiol regenerating agent decreased with increasing methyl substitution. Thus, under conditions where the unsubstituted compound 5a inhibited peroxidation for more than 320 min, alpha-tocopherol worked for 90 min and the trimethylated antioxidant 5g for 60 min only. Sampling of the aqueous phase at intervals during peroxidation using antioxidant 5a showed that N acetylcysteine was continuously oxidized with time to the corresponding disulfide. In the absence of the regenerating agent, compounds 5 inhibited peroxidation for 50-60 min only. A (RO)B3LYP/LANL2DZdp//B3LYP/LANL2DZ model was used for the calculation of homolytic O-H bond dissociation enthalpies (BDE) and adiabatic ionization potentials (IP) of phenolic antioxidants 5. Both BDE (80.6 76.3 kcal/mol) and IP (163.2-156.0 kcal/mol) decrease with increasing methyl substitution. The phenoxyl radical corresponding to phenol 5g gave an intense ESR signal centered at g=2.0099. The H-O bond dissociation enthalpy of the phenol was determined by a radical equilibration method using BHA as an equilibration partner. The observed BDE (77.6+/-0.5 kcal/mol) is in reasonable agreement with calculations (76.3 kcal/mol). As judged by calculated log P values, the lipophilicity of compounds 5 increased slightly when methyl groups were introduced into the phenolic moiety (2.9>C log P<4.2). The capacity of compounds 5a (kinh=3.8x10(5) M-1 s-1) and 5g (kinh=1.5x10(6) M-1 s-1) to inhibit azo initiated autoxidation of styrene in the homogeneous phase (chlorobenzene) was also studied. More efficient regeneration at the lipid-aqueous interphase is the most likely explanation why the intrinsically poorest antioxidant 5a can outperform its analogues as well as alpha-TOC in the two-phase system. Possible mechanisms of regeneration are discussed and evaluated. PMID- 17335241 TI - Palladium-catalyzed heck arylations of allyl alcohols in ionic liquids: remarkable base effect on the selectivity. AB - Pd-catalyzed Heck arylation of allyl alcohols in tetraalkylammonium ionic liquids (ILs) can be made highly selective toward the formation of either aromatic carbonyl compounds or aromatic conjugated alcohols by carefully choosing both the IL and the base. PMID- 17335242 TI - A microwave-assisted synthesis of julolidine-9-carboxamide derivatives and their conversion to chalcogenoxanthones via directed metalation. AB - 9-formyljulolidine was oxidized via a microwave-assisted Willgerodt-Kindler reaction to the N-piperidine or N-morpholine julolidine-9-thioamide. 9-formyl 1,1,7,7-tetramethyljulolidine gave the corresponding N-piperidine tetramethyljulolidine-9-thioamide. The thioamides were converted to the corresponding carboxamides with trifluoroacetic anhydride. The amide group directed ortho-metalation in the julolidine system, but not in the tetramethyljulolidine system. The resulting anion was captured by dichalcogenide electrophiles. The resulting products were converted to chalcogenoxanthones with phosphorus oxychloride and triethylamine (POCl3/Et3N). PMID- 17335243 TI - Structural studies of nonclassical cyclobutylmethyl cations by the ab initio method. AB - Ab initio calculations at the MP2/cc-pVTZ level show that the cyclobutylmethyl cation is a nonclassical sigma-delocalized species, which is distinct from the global minimum C2-symmetric cyclopentyl cation (Schleyer, P. v. R.; Carneiro, J. W. de M.; Koch, W.; Raghavachari, K. J. Am. Chem. Soc. 1989, 111, 5475). Relatively lower level DFT calculations, on the other hand, show that the primary cyclobutylmethyl cation spontaneously collapses into the cyclopentyl cation (Prakash, G. K. S.; Reddy, V. P.; Rasul, G.; Casanova, J.; Olah, G. A. J. Am. Chem. Soc. 1998, 120, 13362). The secondary 1-cyclobutylethyl cation is also a nonclassical carbocation, as shown by calculations at the MP2/cc-pVTZ level. Two structures having energy minima are identified for the latter cation on the potential energy surface. The conformer in which the methyl group is in the exo orientation is a global minimum and is favored over the corresponding endo conformer by 1.2 kcal/mol at the MP2/cc-pVTZ//MP2/cc-pVTZ +ZPE level of calculations. The tertiary 1-cyclobutyl-1-methylethyl cation, at this level of calculations, also involves substantial nonclassical sigma-delocalization, showing that the nonclassical stabilization is more important for cyclobutylmethyl cations relative to the cyclopropylmethyl cations. The 13C NMR chemical shifts obtained from GIAO-CCSD(T)/tzp/dz calculations further substantiate the nonclassical structures for these carbocations. PMID- 17335244 TI - Bioactive macrolides and polyketides from marine dinoflagellates of the genus Amphidinium. AB - Marine microorganisms such as bacteria, cyanobacteria, dinoflagellates, and others have attracted many natural product chemists as the real producers of marine toxins such as fish and algal poisons as well as bioactive substances isolated from marine invertebrates such as sponges and tunicates. Among marine microorganisms, dinoflagellates have proved to be important sources of marine toxins and have been investigated worldwide by natural product chemists. We have continued investigations on chemically interesting and biologically significant secondary metabolites from Amphidinium spp., of a genus of symbiotic marine dinoflagellates separated from inside cells of Okinawan marine flatworms. This review covers the results described in our recent publications on a series of cytotoxic macrolides, designated amphidinolides, and long-chain polyketides isolated from Amphidinium spp. In this review, topics include the isolation, structure elucidation, synthesis, biosynthesis, and bioactivity of amphidinolides and long-chain polyketides. PMID- 17335245 TI - Bromopyrrole carboxamide biosynthetic products from the Caribbean sponge Agelas dispar. AB - Two new bromopyrrole alkaloids, dispyrin (6) and dibromoagelaspongin methyl ether (12), were isolated from the Caribbean sponge Agelas dispar, collected near the Venezuelan island La Blanquilla, and their structures were elucidated from spectroscopic data analysis. Dispyrin (6) contains a novel bromopyrrole tyramine motif that has no precedent in marine natural products chemistry and represents a notable variation from the oroidin class compounds consistently produced by species of Agelas in general. Compounds isolated from Caribbean Agelas species were found to possess a unique biogeographical bromination trend. PMID- 17335247 TI - Stereoisomeric separation and toxicity of a new organophosphorus insecticide chloramidophos. AB - Chloramidophos (CP), O,S-dimethyl-[(2,2,2)-trichloro-1 hydroxyethyl]phosphoramidothioate, is a new organophosphorus pesticide (OP) with two chiral centers each on the phosphorus and carbon atoms. Although CP has been widely used in some provinces of China, it has received very limited attention toward its environmental behaviors, in particular, with regard to stereospecificity. In this study, the stereoisomeric separation and toxicity of CP were investigated. All of the four stereoisomers of CP were successfully separated by high-performance liquid chromatography on a Chiralpak AD column. The stereoisomers (pk 1 to pk 4) were distinguishable on their mass and circular dichroism spectra. The inhibition on acetylcholinesterases (AChE, in vitro) and the acute aquatic toxicity to Daphnia magna (in vivo) tested with optically pure stereoisomers of CP showed its stereoselectivity. The inhibitory potency toward AChE decreased in the order of pk 4 > pk 3 > pk 2 > pk 1. In comparison, the acute toxicity to D. magna was in the order of pk 3 > pk 2 > pk 1 > pk 4. The stereoselectivity was found to be isomer-dependent, with 1.1-18.1-fold differences (in vitro) and 1.2-13-fold differences (in vivo) among the stereoisomers. These results suggest that the overall toxicity of chiral OPs should be assessed using their individual enantiomers. PMID- 17335248 TI - In memoriam: Christopher J. Michejda (December 19, 1937-January 9, 2007). PMID- 17335249 TI - pH-dependent chiral vesicles from enantiomeric sodium 2,3-bis(decyloxy) succinate in aqueous solution. AB - Enantiomeric, twin-tailed, twin-chiral, sodium (2R,3R)-(+)-bis(decyloxy)succinate and sodium (2S,3S)-(-)-bis(decyloxy)succinate have been synthesized and characterized. Surface tension, conductivity, and steady-state fluorescence spectroscopic measurements confirmed the presence of two aggregation concentrations, namely, the critical micellar concentration (CMC) and the critical vesicle concentration (CVC). The compounds behaved as true surfactants, with a CMC of 0.05 mM, and formed vesicles spontaneously in aqueous solution at a CVC of 0.14 mM. The compounds formed myelin figures in contact experiments, suggesting the formation of bilayers in aqueous solution culminating into individual vesicles. The vesicles were of 500-800 nm size and formed egg shells, porous spheres, and multivesicular vesicles, confirmed from transmission electron microscopy and optical microscopic techniques. The vesicles were found to be pH sensitive, were stable in the pH range 6-8, and formed the insoluble diacid at acidic pH due to protonation of the carboxylate head groups. PMID- 17335250 TI - Cell adhesion and growth to Peptide-patterned supported lipid membranes. AB - Lipid vesicles displaying RGD peptide amphiphiles were fused with glass coverslips to control the ability of these surfaces to support cell adhesion and growth. Cell adhesion was prevented on phosphatidylcholine bilayers in the absence of RGD, whereas cells adhered and grew in the presence of accessible RGD amphiphiles. This specific interaction between cells and RGD peptides was further explored in a concentration-dependent fashion by creating surface composition arrays using microfluidics. For the range of concentrations studied adhesion and growth were favored by increased peptide concentration, but this concentration dependence was found to diminish in the higher concentration regions of the array. Developing peptide composition gradients in a membrane environment is demonstrated as an effective method to screen biological probes for cell adhesion and growth. PMID- 17335251 TI - Time-resolved in situ ATR-IR observations of the process of sorption of water into a poly(2-methoxyethyl acrylate) film. AB - A process of water sorption into a biocompatible polymer, poly(2-methoxyethyl acrylate) (PMEA), was investigated by time-resolved, in situ, attenuated total reflection infrared spectroscopy. Evidence for three different types of hydrated water in PMEA, that is, nonfreezing water, freezing bound water, and freezing water, were found. Each hydration structure was elucidated at the functional group level. Nonfreezing water, which never crystallizes, even at -100 degrees C, has a C=O...H-O type of hydrogen bonding interaction with the carbonyl group of PMEA. Freezing bound water, which crystallizes in a heating process below 0 degrees C, interacts with the methoxy moiety in the PMEA side chain terminal. Freezing water, which crystallizes approximately 0 degrees C, has bulk-water-like structure with an O-H...O-H hydrogen bonds network. It has been concluded from the present study that the methoxy moiety in the PMEA side chain terminal plays an important role for the excellent biocompatibility of PMEA. PMID- 17335252 TI - Poly(methyl methacrylate-co-ethyl acrylate) latex particles with poly(ethylene glycol) grafts: structure and film formation. AB - Water-based copolymer dispersions were prepared using methyl methacrylate (MMA), ethyl acrylate (EA) (MMA/EA = 1:2), and a series of nonionic polymerizable surfactants, i.e., "surfmers" based on poly(ethylene glycol)-(meth)acrylates. The latexes were compared with the behavior of a conventionally stabilized (nonionic nonylphenol ethoxylate, NP100 with 84 ethylene oxide units) dispersion with the same MMA-EA composition (PMMAEA). A number of techniques were employed in order to characterize structure, dynamics, and film formation properties: solution/solid-state NMR, dynamic/static light scattering (DLS/SLS), differential scanning calorimetry (DSC), tensile/shear mode dynamic mechanical thermal analysis (DMTA), and atomic force microscopy (AFM). The surfmers were found to be miscible with the MMA-EA copolymer at room temperature, with 46-85 mol % of the reacted surfmer detected at the particle surfaces, and the remaining part buried in the particle bulk. In contrast, the NP100 surfactant formed a separate interphase between the copolymer particles with no mixing detected at room temperature or at 90 degrees C. For a 4.0% dry weight concentration, NP100 phase separated and further crystallized at room temperature over a period of several months. Composition fluctuations related to a limited blockiness on a length scale above approximately 2 nm were detected for PMMAEA particles, whereas the surfmer particles were found to be homogeneous also below this limit. On a particle-particle level, the dispersions tended to form colloidal crystals unless hindered by a broadened particle size distribution or, in the case of PMMAEA, by the action of NP100. Finally, a surface roughness (Rq) master plot was constructed for data above the glass transition temperature (Tg) from Tg + 11 degrees C to Tg + 57 degrees C and compared with the complex shear modulus over 11 frequency decades. Shift factors from the 2 methods obeyed the same Williams Landel-Ferry (WLF) temperature dependence, thus connecting the long-time surface flattening process to the rheological behavior of the copolymer. PMID- 17335253 TI - Electrically driven flow near a colloidal particle close to an electrode with a Faradaic current. AB - To elucidate the nature of processes involved in electrically driven particle aggregation in steady fields, flows near a charged spherical colloidal particle next to an electrode were studied. Electrical body forces in diffuse layers near the electrode and the particle surface drive an axisymmetric flow with two components. One is electroosmotic flow (EOF) driven by the action of the applied field on the equilibrium diffuse charge layer near the particle. The other is electrohydrodynamic (EHD) flow arising from the action of the applied field on charge induced in the electrode polarization layer. The EOF component is proportional to the current density and the particle surface (zeta) potential, whereas our scaling analysis shows that the EHD component scales as the product of the current density and applied potential. Under certain conditions, both flows are directed toward the particle, and a superposition of flows from two nearby particles provides a mechanism for aggregation. Analytical calculations of the two flow fields in the limits of infinitesimal double layers and slowly varying current indicate that the EOF and EHD flow are of comparable magnitude near the particle whereas in the far field the EHD flow along the electrode is predominant. Moreover, the dependence of EHD flow on the applied potential provides a possible explanation for the increased variability in aggregation velocities observed at higher field strengths. PMID- 17335254 TI - Interactions at the surface of organophilic-modified laponites: a multinuclear solid-state NMR study. AB - Organically modified clays are largely employed in the preparation of nanostructured materials. The structural and dynamic characterization of the clay surface appears very important in the perspective of understanding the molecular mechanisms determining the improvement of the material properties. To this aim, in this work, a synthetic clay, Laponite, was studied in its untreated hydrophilic Na+-form, after ion exchange with alkylammonium cations and after subsequent grafting reaction with an alkoxysilane. These three samples were characterized by IR, SEM, TGA, and X-ray techniques and were deeply investigated by means of a wide combination of 29Si, 13C, and 1H high- and low-resolution solid-state NMR experiments. The grafting reaction with alkoxysilanes, occurring at the clay platelet edges, resulted in a reduction of the clay inter-platelet distances, and in an increased disorder in both the arrangement of the platelets and the conformational structure of the intercalated organic cation chains, probably due to the relative twisting of adjacent platelets. PMID- 17335255 TI - Influence of monolayer state on spectroscopy and photoisomerization of an amphiphilic styryl-pyridinium dye on a solid substrate. AB - The spectroscopy and photochromic properties of transferred monolayers of the amphiphilic styryl-pyridinium dye 4-(3',4'-dimethoxystyryl)-N-octadecylpyridinium perchlorate (DMPOP) were studied at different conditions during their transfer. The emission maxima of the monolayers transferred from the air-water interface in the liquid-expanded phase are strongly dependent on the surface pressure applied during the transfer process, even at values when the area per molecule is 2-3 times larger than the area occupied by a chromophore. In monolayers transferred from the liquid-condensed phase, the presence of a different kind of aggregates was observed. The fluorescence emission properties of the monolayers can be reversibly modulated by photoinduced E-Z isomerization. A blue shift up to 72 nm in the emission maximum, depending on the transfer conditions of the films, can be obtained by irradiation with blue light, and partially recovered (a red shift of up to 26 nm) with UV radiation. The rate at which the first process (E-->Z) takes place is drastically reduced in monolayers transferred from the liquid condensed phase as compared to those transferred from the liquid-expanded one. However, the rate of the reverse reaction (Z-->E) is not significantly altered. These properties make DMPOP a promising material for the preparation of Langmuir Blodgett films, whose properties can be effectively controlled by the transfer conditions and subsequently optically modulated, for potential applications as photonics devices for data storage. PMID- 17335256 TI - Self-aggregation of cationic surfactants onto oxidized cellulose fibers and coadsorption of organic compounds. AB - In this work, the adsorption of cationic surfactant and organic solutes on oxidized cellulose fibers bearing different amounts of carboxylic moieties was investigated. The increase in the amount of -COOH groups on cellulose fibers by TEMPO oxidation induced a general rise in surfactant adsorption. For all tested conditions, that is, cellulose oxidation level and surfactant alkyl chain length (C12 and C16), adsorption isotherms displayed a typical three-region shape with inversion of the substrate zeta-potential which was interpreted as reflecting surfactant adsorption and aggregation (admicelles and hemimicelles) on cellulose fibers. The addition of organic solutes in surfactant/cellulose systems induced a decrease in surfactant cac on the cellulose surface thus favoring surfactant aggregation and the formation of mixed surfactant/solute assemblies. Adsorption isotherms of organic solutes on cellulose in surfactant/cellulose/solute systems showed that solute adsorption is strictly correlated to (i) the surfactant concentration, solute adsorption increases up to the surfactant cmc, where solute partitioning between the cellulose surface and free micelles causes a drop in adsorption, and to (ii) solute solubility and functional groups. The specific shape of solutes adsorption isotherms at a fixed surfactant concentration was interpreted using a Frumkin adsorption isotherm, thus suggesting that solute uptake on cellulose fibers is a coadsorption and not a partitioning process. Results presented in this study were compared with those obtained in a previous work investigating solute adsorption in anionic surfactant/cationized cellulose systems to better understand the role of surfactant/solute interactions in the coadsorption process. PMID- 17335257 TI - Synthesis and coating of cobalt ferrite nanoparticles: a first step toward the obtainment of new magnetic nanocarriers. AB - Monodisperse and stable cobalt ferrite (CoFe2O4) nanoparticles (5.4 nm) have been produced, coated with mono- and difunctional phosphonic and hydroxamic acids, and fully characterized (using thermogravimetric analysis (TGA), dynamic light scattering (DLS), IR spectroscopy, transmission electron microscopy (TEM), and superconducting quantum interference device (SQUID) measurements). Cobalt leakage of the coated nanoparticles has been also studied. Magnetic measurements show the possible applications in hyperthermia at low frequencies, and for this reason, water-soluble coated CoFe2O4 can be seen as a first step toward the obtainment of novel systems for biomagnetic applications. PMID- 17335258 TI - Delivery of both active enzyme and bleach from water-in-silicone oil (D(4)) emulsions. AB - Advanced cleaning formulations, such as liquid laundry packages, consist of many components that require a complex mixture of interfacial actives including silicones for foam control, bleach for brightening, and enzymes for stain removal. Many of these ingredients are mutually incompatible, particularly in liquid formulations where they can be in intimate contact over extended periods of time. Solid dispersions of a prototypical bleach, NaBO3, in silicone polyether surfactants were shown to be very stable over time, even in the presence of water in-silicone (D(4)) emulsions containing the enzyme alpha-chymotrypsin. Normally, perborates undergo rapid decomposition on contact with water. The rate of denaturation of the enzyme in the emulsion was similarly unaffected by the presence of the bleach until the emulsion was broken, unlike the case where the polyether surfactant was not present. The polyether surfactant thus protects the perborate from hydration and the enzyme from denaturing on contact with silicone oil until excess water and high shear are applied to the emulsion; protective mechanisms are discussed. PMID- 17335259 TI - Influence of a magnetic field on the formation of magnetite particles via two precipitation methods. AB - An experimental investigation is described on the effects of the presence of a magnetic field during the fabrication of magnetite particles. We considered two well-known synthesis methods: that of Massart [IEEE Trans. Magn. 1981, 17, 1247 1248] for the synthesis of nanometer-sized, monodomain particles; and that of Sugimoto and Matijevic [J. Colloid Interface Sci. 1980, 74, 227-243.] for the fabrication of micrometer-sized multidomain spherical particles. The latter method was studied with two systems of different ionic compositions that lead to two different mechanisms of growth: either growth by aggregation and recrystallization of primary particles or direct crystal growth. When growth was dominated by aggregation of primary units, the magnetic field had a dramatic effect on the morphology, inducing the formation of rodlike particles. Growth dynamics of that system were studied for particles obtained in the presence as well as in the absence of the magnetic field. Particles were also characterized by powder magnetometry, electrophoresis, X-ray diffraction, and optical absorbance techniques. Interestingly, growth dynamics of the rods cross section were comparable to those of the diameter of the spheres. With the exception of the morphology, no other significant difference was found between the rodlike particles and the spheres. PMID- 17335260 TI - Defect-free polymer multilayers prepared via chemoselective immobilization. AB - In this paper, we investigated electrochemical properties of polymer multilayers on gold substrates using impedance spectroscopy. The multilayer was prepared by chemoselective ligation between aldehyde- and oxyamine-functionalized polymers via a layer-by-layer approach. The impedance spectra in a buffer solution in the absence of redox species revealed the formation of highly impermeable and defect free films. The dielectric thickness of the polymer film, which is proportional to the reciprocal of capacitance, linearly increased as the number of deposition layer increased. The defect area of the polymer multilayer was obtained using the faradaic impedance with redox species. The surface coverage of eight polymer layers was determined to be 99.99%. Thus, the layer-by-layer deposition via chemoselective ligation offers a new way to prepare a highly insulating and defect-free polymer layer with finely tunable capacitance as a function of the number of deposition layers. PMID- 17335261 TI - Copolymer-controlled homogeneous precipitation for the synthesis of porous microfibers of alumina. AB - Mesoporous aluminas with a uniform fibrous morphology were synthesized using a copolymer-controlled homogeneous precipitation method under hydrothermal conditions. Scanning electron microscopy, X-ray diffraction, solid-state magic angle spinning nuclear magnetic resonance, transmission electron microscopy, thermogravimetric analysis, nitrogen adsorption, Fourier transform infrared spectrometry, and elemental analysis techniques were used to characterize the samples. The effect of various synthesis conditions on the morphology and mesoporous structure of the alumina fibers was investigated. Such porous alumina microfibers may find applications in nanotechnology and catalysis. They can also be used as advanced high-temperature composite materials and templates for fabrication of fibrous materials of various compositions, such as carbon, transition-metal oxides, and polymers. PMID- 17335262 TI - Effect of mixing on the formation of complexes of hyperbranched cationic polyelectrolytes and anionic surfactants. AB - The effect of different mixing protocols on the charged nature and size distribution of the aqueous complexes of hyperbranched poly(ethylene imine) (PEI) and sodium dodecyl sulfate (SDS) was investigated by electrophoretic mobility and dynamic light scattering measurements at different pH values, polyelectrolyte concentrations, and ionic strengths. It was found that at large excess of the surfactant a colloidal dispersion of individual PEI/SDS nanoparticles forms via an extremely rapid mixing of the components by means of a stop-flow apparatus. However, the application of a less efficient mixing method under the same experimental conditions might result in large clusters of the individual PEI/SDS particles as well as in a more extended precipitation regime compared with the results of stop-flow mixing protocol. The study revealed that the larger the charge density and concentration of the PEI, the more pronounced the effect of mixing becomes. It can be concluded that an efficient way to avoid precipitation in the solutions of oppositely charged polyelectrolytes and surfactants might be provided by extending the range of kinetically stable colloidal dispersion of polyelectrolyte/surfactant nanoparticles via the application of appropriate mixing protocols. PMID- 17335263 TI - Fractal-type particle gel formed from gelatin + starch solution. AB - Using confocal microscopy and small-deformation rheology, we demonstrate the formation of stable thermoreversible gelatin-based gels with colloidal fractal type microstructure. The opaque particle gels were made by cooling of transparent mixed aqueous solutions of gelatin (1-3 wt %) and starch (7 wt %) from 40 to 24 degrees C. The mechanism involves starch-induced gelatin self-association into phase-separated gelatin-rich microgel particles, followed by diffusion-limited cluster aggregation into a particle gel network. PMID- 17335264 TI - Charge transport in cellular nanoparticle networks: meandering through nanoscale mazes. AB - The transport of electrons through topologically complex two-dimensional Au nanoparticle networks has been investigated using a combination of low temperature (4.5 K) direct current I(V) measurements and numerical simulations. Intricate, spatially correlated nanostructured networks were formed via spin casting. The topological complexity of the nanoparticle assemblies produces I(V) curves associated with nonlinearity exponents, zeta approximately 4.0. Simulations based on tunneling transport in sparse and inhomogeneous planar networks are used to elucidate the influence of topology on the value of zeta. PMID- 17335265 TI - Multimodal biomedical imaging with asymmetric single-walled carbon nanotube/iron oxide nanoparticle complexes. AB - Magnetic iron oxide nanoparticles and near-infrared (NIR) fluorescent single walled carbon nanotubes (SWNT) form heterostructured complexes that can be utilized as multimodal bioimaging agents. Fe catalyst-grown SWNT were individually dispersed in aqueous solution via encapsulation by oligonucleotides with the sequence d(GT)15, and enriched using a 0.5 T magnetic array. The resulting nanotube complexes show distinct NIR fluorescence, Raman scattering, and visible/NIR absorbance features, corresponding to the various nanotube species. AFM and cryo-TEM images show DNA-encapsulated complexes composed of a approximately 3 nm particle attached to a carbon nanotube on one end. X-ray diffraction (XRD) and superconducting quantum interference device (SQUID) measurements reveal that the nanoparticles are primarily Fe2O3 and superparamagnetic. The Fe2O3 particle-enriched nanotube solution has a magnetic particle content of approximately 35 wt %, a magnetization saturation of approximately 56 emu/g, and a magnetic relaxation time scale ratio (T1/T2) of approximately 12. These complexes have a longer spin-spin relaxation time (T2 approximately 164 ms) than typical ferromagnetic particles due to the smaller size of their magnetic component while still retaining SWNT optical signatures. Macrophage cells that engulf the DNA-wrapped complexes were imaged using magnetic resonance imaging (MRI) and NIR mapping, demonstrating that these multifunctional nanostructures could potentially be useful in multimodal biomedical imaging. PMID- 17335266 TI - High-performance nano-Schottky diodes and nano-MESFETs made on single CdS nanobelts. AB - Nano-Schottky diodes and nanometal-semiconductor field-effect transistors (MESFETs) on single CdS nanobelts (NBs) have been fabricated and studied. The Au/CdS NB Schottky diodes have very low reverse current density ( approximately 3.0 x 10-5 A.cm-2 at -10 V reverse bias) and the highest on/off current ratio (approximately 108) reported so far for nano-Schottky diodes. The single CdS NB MESFETs exhibit n-channel normally on (depletion) mode, low threshold voltage (approximately -1.56 V), high transconductance ( approximately 3.5 microS), low subthreshold swing ( approximately 45 mV/dec), and the highest on/off current ratio (approximately 2 x 108) reported so far for nanofield-effect transistors. We also show that the absolute value of threshold voltage for a metal-insulator semiconductor field-effect transistor made on a single CdS NB can be reduced from approximately 12.5 to approximately 0.4 V and its transconductance can be increased from approximately 0.2 to approximately 3.2 microS by adding an extra Au Schottky contact on the CdS NB, the mechanism of which is discussed. PMID- 17335267 TI - Growth of high-density titanium silicide nanowires in a single direction on a silicon surface. AB - Understanding the growth mechanisms of nanowires is essential for their successful implementation in advanced devices applications. In situ ultrahigh vacuum transmission electron microscopy has been applied to elucidate the interaction mechanisms of titanium disilicide nanowires (TiSi2 NWs) on Si(111) substrate. Two phenomena were observed: merging of the two NWs in the same direction, and collapse of one NW on a competing NW in a different direction when they meet at the ends. On the other hand, as one NW encounters the midsection of the other NW in a different direction, it recedes in favor of bulging of the other NW at the midsection. Since crystallographically the nanowires are favored to grow on Si(110) only in the [1 -1 0] direction, this crucial information has been fruitfully exploited to focus on the growth of a high density of long and high-aspect-ratio Ti silicide NWs parallel to the surface on Si(110) in a single direction. The achievement in growth of high-density NWs in a single direction represents a significant advance in realizing the vast potential for applications of silicide NWs in nanoelectronics devices. PMID- 17335268 TI - Probing the local coordination environment for transition metal dopants in zinc oxide nanowires. AB - It is hypothesized that a highly ordered, relatively defect-free dilute magnetic semiconductor system should act as a weak ferromagnet. Transition-metal-doped ZnO nanowires, being single crystalline, single domain, and single phase, are used here as a model system for probing the local dopant coordination environments using X-ray absorption spectroscopy and diffraction. Our X-ray spectroscopic data clearly show that the dopant resides in a uniform environment, and that the doping does not induce a large degree of disorder in the nanowires. This homogeneous nature of the doping inside the oxide matrix correlates well with observed weakly ferromagnetic behavior of the nanowires. PMID- 17335269 TI - Systematic investigation of the thermodynamics of HSA adsorption to N-iso propylacrylamide/N-tert-butylacrylamide copolymer nanoparticles. Effects of particle size and hydrophobicity. AB - Nanoparticles in biological fluids almost invariably become coated with proteins that may confer nanomedical and nanotoxicological effects. Understanding these effects requires quantitative measurements using simple systems. Adsorption of HSA to copolymer nanoparticles of varying hydrophobicity and curvature was studied using ITC, yielding stoichiometry, affinity, and enthalpy changes upon binding. The hydrophobicity was controlled via the co-monomer ratio, N-iso propylacrylamide/N-tert-butylacrylamide. The most hydrophobic particles become fully covered with a single layer of protein, except at high curvature. PMID- 17335270 TI - Twin-free uniform epitaxial GaAs nanowires grown by a two-temperature process. AB - We demonstrate vertically aligned epitaxial GaAs nanowires of excellent crystallographic quality and optimal shape, grown by Au nanoparticle-catalyzed metalorganic chemical vapor deposition. This is achieved by a two-temperature growth procedure, consisting of a brief initial high-temperature growth step followed by prolonged growth at a lower temperature. The initial high-temperature step is essential for obtaining straight, vertically aligned epitaxial nanowires on the (111)B GaAs substrate. The lower temperature employed for subsequent growth imparts superior nanowire morphology and crystallographic quality by minimizing radial growth and eliminating twinning defects. Photoluminescence measurements confirm the excellent optical quality of these two-temperature grown nanowires. Two mechanisms are proposed to explain the success of this two temperature growth process, one involving Au nanoparticle-GaAs interface conditions and the other involving melting-solidification temperature hysteresis of the Au-Ga nanoparticle alloy. PMID- 17335271 TI - Surface spin-valve effect. AB - We report an observation of spin-valve-like hysteresis within a few atomic layers at a ferromagnetic interface. We use phonon spectroscopy of nanometer-sized point contacts as an in situ probe to study the mechanism of the effect. Distinctive energy phonon peaks for contacts with dissimilar nonmagnetic outer electrodes allow localizing the observed spin switching to the top or bottom interfaces for nanometer thin ferromagnetic layers. The mechanism consistent with our data is energetically distinct atomically thin surface spin layers that can form current- or field-driven surface spin-valves within a single ferromagnetic film. PMID- 17335272 TI - Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods. AB - We demonstrate the use of gold nanorods as bright contrast agents for two-photon luminescence (TPL) imaging of cancer cells in a three-dimensional tissue phantom down to 75 mum deep. The TPL intensity from gold-nanorod-labeled cancer cells is 3 orders of magnitude brighter than the two-photon autofluorescence (TPAF) emission intensity from unlabeled cancer cells at 760 nm excitation light. Their strong signal, resistance to photobleaching, chemical stability, ease of synthesis, simplicity of conjugation chemistry, and biocompatibility make gold nanorods an attractive contrast agent for two-photon imaging of epithelial cancer. PMID- 17335273 TI - Identification of quantum dot bioconjugates and cellular protein co-localization by hybrid gel blotting. AB - New approaches are needed to address the interaction of nanoparticles and cellular proteins at the molecular level. We present a modification of PAGE co immunoprecipitation, QD-based PA-AGE electrophoresis blotting, and apply this to identify quantum dot (QD) bioconjugate-cellular protein association. This method provides the capability to isolate and evaluate the action of QD bioconjugate protein complexes in intact cells and to correlate these identified interactions with their location in cells. PMID- 17335274 TI - Synthesis and characterization of a new Tiara Pd(II) thiolate complex, [Pd(SC12H25)2]6, and its solution-phase thermolysis to prepare nearly monodisperse palladium sulfide nanoparticles. AB - A new tiara Pd(II) thiolate complex, [Pd(SC12H25)2]6, has been synthesized and fully characterized by X-ray single crystal analysis, elemental analysis, MALDI, 1H NMR, powder XRD, IR, Raman, and UV/vis. It was found that, in each complex cluster, the six palladium atoms form a nearly planar hexagonal ring and the adjacent palladium atoms are bridged by sulfur atoms from both sides. Then the complex was further used as a single-source precursor to prepare nearly monodisperse palladium sulfide (PdS) nanoparticles through the high-temperature induced decomposition in diphenyl ether. The obtained nanoparticles are 2.87 +/- 0.51 nm in diameter and protected by a layer of thiolate species on the surface. PMID- 17335275 TI - Conformational flexibility in 2,2'-Dioxybiphenyl-chloro-cyclotetraphosphazenes and its relevance to polyphosphazene analogues. AB - The reaction of the cyclotetraphosphazene, [N4P4Cl8], with the difunctional reagent, 2,2'-biphenol, in the presence of potassium carbonate in acetone produced the spiro-substituted derivatives, 2,2' dioxybiphenylhexachlorocyclotetraphosphazene, bis(2,2'-dioxybiphenyl)tetrachloro cyclotetraphosphazene, and tris(2,2'-dioxybiphenyl)dichlorocyclotetraphosphazene. Both cis and trans geometrical isomers of the bis compound are observed. Although chromatographic separation of these was unsuccessful, a sample of the trans isomer was obtained by fractional crystallization. The compounds all show non first-order 31P NMR spectra which were simulated to extract the spectral parameters. Single-crystal X-ray structures of both the trans bis and the tris compounds show that the cyclophosphazene rings exhibit conformational flexibility which gives rise to different crystalline forms being obtained from the same solvent systems. Crystals of trans-bis(2,2'-dioxybiphenyl)tetrachloro cyclotetraphosphazene were obtained in two different space groups: Pnna (orthorhombic) and P21/n (monoclinic). In the orthorhombic structure, the dominant (72%) conformation of one phosphazene ring is a chair form, and the other (28%) resembles a boat. While for the monoclinic structure, the ring is virtually flat with an oval shape. In both cases the dioxybiphenyl groups are found in R and S configurations in the same molecule and are pi stacked in columns (Pnna) or involved in pi-pi or pi-H interactions (P21/n), thus anchoring the phosphorus atoms of the cyclotetraphosphazenes but still allowing flexibility in the ring conformations. Three crystalline modifications of tris(2,2' dioxybiphenyl)dichloro-cyclotetraphosphazene were obtained: two in space group P (triclinic), which contained two molecules of dichloromethane in the unit cell, and one solvent-free form in space group P21/n (monoclinic). The cyclophosphazene rings exhibit puckered conformations with the trans-dioxybiphenyl moieties having opposing RS or SR conformations. DFT calculations were carried out on each of the phosphazene ring conformations in trans-bis(2,2' dioxybiphenyl)tetrachlorocyclotetraphosphazene identified from the X-ray diffraction analysis. It is concluded that intermolecular interactions (i.e., pi pi or pi-H) between the dioxybiphenyl groups is a factor that modifies the nature of the potential energy surface between the different conformers. The flexibility of the phosphazene ring is supported computationally through the calculated low energy barriers and experimentally through the highly disordered phosphazene ring conformations observed in the solid state. The results on 2,2'-dioxybiphenyl substituted cyclotetraphosphazenes provide evidence that microcrystalline domains in their 2,2'-dioxybiphenyl-substituted polyphosphazene analogues will be generated by similar pi-pi and pi-H interactions. PMID- 17335276 TI - Synthesis and catalytic properties in olefin epoxidation of novel iron(II) complexes with pyridine-containing macrocycles bearing an aminopropyl pendant arm. AB - Three novel iron(II) complexes with pyridine-containing macrocycles bearing an aminopropyl pendant arm were synthesized and characterized. Crystal structures of two of the complexes revealed high-spin iron(II) centers coordinated to the five ligand nitrogen atoms with no coordination of either the solvent molecules or anions, resulting in an unusual square-pyramidal geometry. Related tetradentate ligand CRH formed a low-spin iron(II) complex (meso form was structurally characterized) with a planar arrangement of the four nitrogen atoms from the macrocycle and two axial acetonitrile molecules. Similarly to the corresponding nickel and copper complexes of the pentadentate ligands, the protonation of the amino group on the ligand arm in iron(II) complexes was found to be reversible. Spectral changes and magnetic susceptibility measurements indicated that a change in the geometry and spin state of the metal center is associated with this acid base process. In the presence of noncoordinating acids (e.g., triflic acid), these complexes, as well as their nonmethylated analogue, can efficiently catalyze the epoxidation of cyclooctene and 1-decene under mild conditions, using hydrogen peroxide as the oxidant. However, in the deprotonated form or in the presence of coordinating acids like HCl, no epoxidation occurs. PMID- 17335277 TI - Photostability versus photodegradation in the excited-state intramolecular proton transfer of nitro enamines: competing reaction paths and conical intersections. AB - The phototautomerization mechanism of a model nitro enamine (NEA) chromophore (incorporated in the structure of a highly photolabile pesticide, tetrahydro-2 (nitromethylene)-2H-1,3-thiazine) has been studied using complete active space self-consistent field reaction path computations. The optically accessible 1pipi* excited state of NEA involves separation of charge and correlates diabatically with the ground state of the tautomerized acinitro imine (ANI) form. For optimum photostabilization, the 1pipi* state of NEA should be S1: in this case, the tautomer would be efficiently formed via a diabatic intramolecular proton transfer pathway passing through an S1/S0 conical intersection, followed by a facile thermal back proton-transfer reaction. However, in NEA itself the lowest excited states correspond to nitro group 1npi* states, and there are additional surface crossings that provide a mechanism for populating the 1npi* manifold. The above results indicate that the high photolability observed for the pesticide [Kleier, D.; Holden, I.; Casida, J. E.; Ruzo, L. O. J. Agric. Food Chem. 1985, 33, 998-1000] has to be ascribed to photochemistry originating on the 1npi* manifold of states, populated indirectly from the 1pipi* state. PMID- 17335278 TI - Cluster core controlled reactions of substitution of terminal bromide ligands by triphenylphosphine in octahedral rhenium chalcobromide complexes. AB - Reactions of rhenium chalcobromides Cs4[{Re6(mu3-S)8}Br6].2H2O, Cs3[{Re6(mu3 Se)8}Br6].2H2O, Cs3[{Re6(mu3-Q)7(mu3-Br)}Br6].H2O (Q = S, Se), and K2[{Re6(mu3 S)6(mu3-Br)2}Br6] with molten triphenylphosphine (PPh3) have resulted in a family of novel molecular hybrid inorganic-organic cluster compounds. Six octahedral rhenium cluster complexes containing PPh3 ligands with general formula [{Re6(mu3 Q)8-n(mu3-Br)n}(PPh3)4-nBrn+2] (Q = S, n = 0, 1, 2; Q = Se, n = 0, 1) have been synthesized and characterized by X-ray single-crystal diffraction and elemental analyses, 31P{1H} NMR, luminescent measurements, and quantum-chemical calculations. It was found that the number of terminal PPh3 ligands in the complexes is controlled by the composition and consequently by the charge of the cluster core {Re6Q8-nBrn}n+2. In crystal structures of the complexes with mixed chalcogen/bromine ligands in the cluster core all positions of a cube [Q8-nBrn] are ordered and occupied exclusively by Q or Br atoms. Luminescence characteristics of the compounds trans-[{Re6Q8}(PPh3)4Br2] and fac [{Re6Se7Br}(PPh3)3Br3] (Q = S, Se) have been investigated in CH2Cl2 solution and the broad emission spectra in the range of 600-850 nm were observed. PMID- 17335279 TI - A fluorescent sensor for imaging reversible redox cycles in living cells. PMID- 17335280 TI - Ultraviolet resonance Raman evidence for utilization of the heme 6-propionate hydrogen-bond network in signal transmission from heme to protein in Ec DOS protein. AB - The direct oxygen sensor protein from Escherichia coli (Ec DOS) is a heme-based signal transducer protein responsible for phosphodiesterase (PDE) activity. Binding of either O2 or CO molecule to a reduced heme enhances the PDE activity toward 3',5'-cyclic diguanylic acid. We report ultraviolet resonance Raman (UVRR) spectroscopic investigations of the reduced, O2- and CO-bound forms of heme-bound PAS domain of Ec DOS. The UVRR results show that heme discriminates different ligands, resulting in altered conformations in the protein moiety. Specifically, the environment around Trp53 that contacts the 2-vinyl group of heme, is changed to a more hydrophobic environment by O2 binding, whereas it is changed to a more hydrophilic environment by CO-binding. In addition, the PDE activity of the O2- and CO-bound forms for the Trp53Phe mutant is significantly decreased compared with that of the wild type (WT), demonstrating the importance of Trp53 for the catalytic reaction. On the other hand, the binding of O2 or CO to the heme produces drastic changes in the Tyr126 of Ibeta-strand at the surface of the sensor domain. Furthermore, we found that Asn84 forms a hydrogen bond with Tyr126 either in the O2- or CO-bound forms but not in the reduced form. Finally, the PDE activities of the ligand-bound forms for Asn84Val and Tyr126Phe mutants are significantly reduced as compared with that of WT, suggesting the importance of the hydrogen-bonding network from heme 6-propionate to Tyr126 through Asn84 in signal transmission. PMID- 17335281 TI - Anaerobic sulfatase-maturating enzymes: radical SAM enzymes able to catalyze in vitro sulfatase post-translational modification. PMID- 17335282 TI - XeOF2, F2OXeN identical with CCH3, and XeOF2.nHF: rare examples of Xe(IV) oxide fluorides. AB - The syntheses of XeOF2, F2OXeNCCH3, and XeOF2.nHF and their structural characterizations are described in this study. All three compounds are explosive at temperatures approaching 0 degrees C. Although XeOF2 had been previously reported, it had not been isolated as a pure compound. Xenon oxide difluoride has now been characterized in CH3CN solution by 19F, 17O, and 129Xe NMR spectroscopy. The solid-state Raman spectra of XeOF2, F2OXeNCCH3, and XeOF2.nHF have been assigned with the aid of 16O/18O and 1H/2H enrichment studies and electronic structure calculations. In the solid state, the structure of XeOF2 is a weakly associated, planar monomer, ruling out previous speculation that it may possess a polymeric chain structure. The geometry of XeOF2 is consistent with a trigonal bipyramidal, AX2YE2, VSEPR arrangement that gives rise to a T-shaped geometry in which the two free valence electron lone pairs and Xe-O bond domain occupy the trigonal plane and the Xe-F bond domains are trans to one another and perpendicular to the trigonal plane. Quantum mechanical calculations and the Raman spectra of XeOF2.nHF indicate that the structure likely contains a single HF molecule that is H-bonded to oxygen and also weakly F-coordinated to xenon. The low-temperature (-173 degrees C) X-ray crystal structure of F2OXeNCCH3 reveals a long Xe-N bond trans to the Xe-O bond and a geometrical arrangement about xenon in which the atoms directly bonded to xenon are coplanar and CH3CN acts as a fourth ligand in the equatorial plane. The two fluorine atoms are displaced away from the oxygen atom toward the Xe-N bond. The structure contains two sets of crystallographically distinct F2OXeNCCH3 molecules in which the bent Xe-N-C moiety lies either in or out of the XeOF2 plane. The geometry about xenon is consistent with an AX2YZE2 VSEPR arrangement of bond pairs and electron lone pairs and represents a rare example of a Xe(IV)-N bond. PMID- 17335283 TI - Continuous structural evolution of calcium carbonate particles: a unifying model of copolymer-mediated crystallization. AB - Two double-hydrophilic block copolymers, each comprising a nonionic block and an anionic block comprising pendent aromatic sulfonate groups, were used as additives to modify the crystallization of CaCO3. Marked morphological changes in the CaCO3 particles were observed depending on the reaction conditions used. A poly(ethylene oxide)-b-poly(sodium 4-styrenesulfonate) diblock copolymer was particularly versatile in effecting a morphological change in calcite particles, and a continuous structural transition in the product particles from polycrystalline to mesocrystal to single crystal was observed with variation in the calcium concentration. The existence of this structural sequence provides unique insight into the mechanism of polymer-mediated crystallization. We propose that it reflects continuity in the crystallization mechanism itself, spanning the limits from nonoriented aggregation of nanoparticles to classical ion-by-ion growth. The various pathways to polycrystalline, mesocrystal, and single-crystal particles, which had previously been considered to be distinct, therefore all form part of a unifying crystallization framework based on the aggregation of precursor subunits. PMID- 17335284 TI - Antibacterial activity of plastics coated with silver-doped organic-inorganic hybrid coatings prepared by sol-gel processes. AB - Silver-doped organic-inorganic hybrid coatings were prepared starting from tetraethoxysilane- and triethoxysilane-terminated poly(ethylene glycol)-block polyethylene by the sol-gel process. They were applied as a thin layer (0.6-1.1 microm) to polyethylene (PE) and poly(vinyl chloride) (PVC) films and the antibacterial activity of the coated films was tested against Gram-negative (Escherichia coli ATCC 25922) and Gram-positive (Staphylococcus aureus ATCC 6538) bacteria. The effect of several factors (such as organic-inorganic ratio, type of catalyst, time of post-curing, silver ion concentration, etc.) was investigated. Measurements at different contact times showed a rapid decrease of the viable count for both tested strains. The highest antibacterial activity [more than 6 log reduction within 6 h starting from 106 colony-forming units (cfu) mL-1] was obtained for samples with an organic-inorganic weight ratio of 80:20 and 5 wt % silver salt with respect to the coating. For the coatings prepared by an acid catalyzed process, a high level of permanence of the antibacterial activity of the coated films was demonstrated by repeatedly washing the samples in warm water or by immersion in physiological saline solution at 37 degrees C for 3 days. The release of silver ions per square meter of coating is very similar to that previously observed for polyamides filled with metallic silver nanoparticles; however, when compared on the basis of Ag content, the concentration of silver ions released from the coating is much higher than that released from 1 mm thick specimens of polyamide (PA) filled with silver nanoparticles. Transparency and good adhesion of the coating to PE and PVC plastic substrates without any previous surface treatment are further interesting features. PMID- 17335285 TI - Palmitic acid-modified poly-L-lysine for non-viral delivery of plasmid DNA to skin fibroblasts. AB - Palmitic acid conjugates of poly-L-lysine (PLL-PA) were prepared, and their ability to deliver plasmid DNA into human skin fibroblasts was evaluated in vitro. The conjugates were capable of condensing a 4.7 kb plasmid DNA into 50-200 nm particles (mean +/- SD = 112 +/- 34 nm), which were slightly smaller than the particles formed by PLL (mean +/- SD = 126 +/- 51 nm). Both PLL and PLL-PA were readily taken up by the cells, but PLL-PA delivered the plasmid DNA into a higher proportion of cells. DNA delivery was found to be reduced by endocytosis inhibitor Brefeldin A, suggesting an active mechanism of particle uptake. Using enhanced green fluorescent protein (EGFP) as a reporter gene, PLL-PA was found to give the highest number of EGFP-positive cells among several carriers tested, including polyethyleneimine, Lipofectamine-2000, and an adenovirus. Although some carriers gave a higher percentage of EGFP-positive cells than PLL-PA, they were also associated with higher toxicities. We conclude that PLL-PA is a promising gene carrier for non-viral modification of human fibroblasts. PMID- 17335286 TI - Nanobiotechnology: protein-nanomaterial interactions. AB - We review recent research that involves the interaction of nanomaterials such as nanoparticles, nanowires, and carbon nanotubes with proteins. We begin with a focus on the fundamentals of the structure and function of proteins on nanomaterials. We then review work in three areas that exploit these interactions: (1) sensing, (2) assembly of nanomaterials by proteins and proteins by nanomaterials, and (3) interactions with cells. We conclude with the identification of challenges and opportunities for the future. PMID- 17335287 TI - Use of damaged DNA and dNTP substrates by the error-prone DNA polymerase X from African swine fever virus. AB - The structural specificity that translesion DNA polymerases often show for a particular class of lesions suggests that the predominant criterion of selection during their evolution has been the capacity for lesion tolerance and that the error-proneness they display when copying undamaged templates may simply be a byproduct of this adaptation. Regardless of selection criteria/evolutionary history, at present both of these properties coexist in these enzymes, and both properties confer a fitness advantage. The repair polymerase, Pol X, encoded by the African swine fever virus (ASFV) is one of the most error-prone polymerases known, leading us to previously hypothesize that it may work in tandem with the exceptionally error-tolerant ASFV DNA ligase to effect viral mutagenesis. Here, for the first time, we test whether the error-proneness of Pol X is coupled with a capacity for lesion tolerance by examining its ability to utilize the types of damaged DNA and dNTP substrates that are expected to be relevant to ASFV. We (i) test Pol X's ability to both incorporate opposite to and extend from ubiquitous oxidative purine (7,8-dihydro-8-oxoguanine), oxidative pyrimidine (5,6-dihydroxy 5,6-dihydrothymine), and noncoding (AP site) lesions, in addition to 5,6 dihydrothymine, (ii) determine the catalytic efficiency and dNTP specificity of Pol X when catalyzing incorporation opposite to, and when extending from, 7,8 dihydro-8-oxoguanine in a template/primer context, and (iii) quantitate Pol X catalyzed incorporation of the damaged nucleotide 8-oxo-dGTP opposite to undamaged templates in the context of both template/primer and a single nucleotide gap. Our findings are discussed in light of ASFV biology and the mutagenic DNA repair hypothesis described above. PMID- 17335288 TI - Solution structure of the Rhodobacter sphaeroides PufX membrane protein: implications for the quinone exchange and protein-protein interactions. AB - PufX membrane protein is found in Rhodobacter species of purple photosynthetic bacteria and has been known to play an essential role in ubiquinone/ubiquinol exchange between the reaction center and cytochrome bc1 complex and also contribute to the dimerization of the reaction center-light-harvesting core complex. We have determined the solution structure of the Rhodobacter sphaeroides PufX using multidimensional NMR spectroscopy. The PufX, functionally expressed in Escherichia coli, forms a stable alpha helix consisting of 21 residues over the central transmembrane domain. The overall structure of the PufX is very similar to those of the LH1 alpha- and beta-polypeptides from Rhodospirillum rubrum and LH2 polypeptides. A short segment (Lys28-Gly35) rich in Gly and Ala residues revealed a relatively fast exchange between the backbone amide protons and deuteriums in the hydroxyl groups of the solvent, indicating that the backbone of this segment is more easily accessible to the surrounding solvent molecules compared to those of its neighboring portions. The Gly- and Ala-rich segment is located in the middle of the central helix and forms an extensive groove-like conformation on the surface with the neighboring residues, where the residues with large side chains are aligned on one side of the helix, and small residues are aligned on the other face. Such a structural motif may serve as a functional site responsible for ubiquinol transport from the core complex to the membrane phase and for sequence-specific helix-helix interactions with the neighboring polypeptides. PMID- 17335289 TI - Protein conformational changes of Agrobacterium phytochrome Agp1 during chromophore assembly and photoconversion. AB - Phytochromes are widely distributed photochromic biliprotein photoreceptors. Typical bacterial phytochromes such as Agrobacterium Agp1 have a C-terminal histidine kinase module; the N-terminal chromophore module induces conformational changes in the protein that lead to modulation of kinase activity. We show by protein cross-linking that the C-terminal histidine kinase module of Agp1 mediates stable dimerization. The fragment Agp1-M15, which comprises the chromophore module but lacks the histidine kinase module, can also form dimers. In this fragment, dimer formation was stronger for the far-red-absorbing form Pfr than for the red-absorbing form Pr. The same or similar behavior was found for Agp1-M15Delta9N and Agp1-M15Delta18N, which lack 9 and 18 amino acids of the N terminus, respectively. The fragment Agp1-M20, which is derived from Agp1-M15 by truncation of the C-terminal "PHY domain" (191 amino acids), can also form dimers, but dimerization is independent of irradiation conditions. The cross linking data also showed that the PHY domain is in tight contact with Lys 16 of the protein and that the nine N-terminal amino acids mediate oligomer formation. Limited proteolysis shows that the hinge region between the chromophore module and the histidine kinase and a part of the PHY domain become exposed upon Pr to Pfr photoconversion. PMID- 17335290 TI - Inhibition of lipid A biosynthesis as the primary mechanism of CHIR-090 antibiotic activity in Escherichia coli. AB - The deacetylation of UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine (UDP-3 O-acyl-GlcNAc) by LpxC is the committed reaction of lipid A biosynthesis. CHIR 090, a novel N-aroyl-l-threonine hydroxamic acid, is a potent, slow, tight binding inhibitor of the LpxC deacetylase from the hyperthermophile Aquifex aeolicus, and it has excellent antibiotic activity against Pseudomonas aeruginosa and Escherichia coli, as judged by disk diffusion assays. We now report that CHIR 090 is also a two-step slow, tight-binding inhibitor of E. coli LpxC with Ki = 4.0 nM, Ki* = 0.5 nM, k5 = 1.9 min-1, and k6 = 0.18 min-1. CHIR-090 at low nanomolar levels inhibits LpxC orthologues from diverse Gram-negative pathogens, including P. aeruginosa, Neisseria meningitidis, and Helicobacter pylori. In contrast, CHIR-090 is a relatively weak competitive and conventional inhibitor (lacking slow, tight-binding kinetics) of LpxC from Rhizobium leguminosarum (Ki = 340 nM), a Gram-negative plant endosymbiont that is resistant to this compound. The KM (4.8 microM) and the kcat (1.7 s-1) of R. leguminosarum LpxC with UDP-3-O [(R)-3-hydroxymyristoyl]-N-acetylglucosamine as the substrate are similar to values reported for E. coli LpxC. R. leguminosarum LpxC therefore provides a useful control for validating LpxC as the primary target of CHIR-090 in vivo. An E. coli construct in which the chromosomal lpxC gene is replaced by R. leguminosarum lpxC is resistant to CHIR-090 up to 100 microg/mL, or 400 times above the minimal inhibitory concentration for wild-type E. coli. Given its relatively broad spectrum and potency against diverse Gram-negative pathogens, CHIR-090 is an excellent lead for the further development of new antibiotics targeting the lipid A pathway. PMID- 17335293 TI - The role of induction therapy for resectable non-small cell lung cancer. AB - Lung cancer is the leading cause of cancer death among men and women in the US. Surgical resection is potentially curative; however, even after complete resection many patients experience systemic recurrence and subsequently die of their disease. As a means of reducing the chances of recurrence there has been significant interest in combining chemotherapy with surgical resection. Recently, several large phase III clinical trials have demonstrated a significant survival benefit with adjuvant or postoperative cisplatin-based chemotherapy. Use of preoperative or induction chemotherapy has also been an area of active investigation; however, the trials that have demonstrated a survival benefit were small in size, and there has not been widespread acceptance of this treatment approach. The trials of induction chemoradiotherapy have generally been performed in patients with locally advanced disease, frequently in patients with involvement of the level 2 mediastinal lymph nodes (N2). The results of the recent US Intergroup trial, 0139, which compared induction chemoradiotherapy followed by surgical resection versus nonsurgical therapy with chemoradiotherapy in patients with resectable stage IIIA-N2 disease, revealed equivalent overall survival between the two treatment approaches. The results of an unplanned subset analysis of patients who were treated with lobectomy in the surgical arm have generated significant interest and debate. When the strategy of induction therapy is used, pathological clearance of the mediastinal lymph nodes is a significant prognostic factor for overall survival. Current investigations are attempting to determine the optimal method of assessing this critical prognostic factor. The toxicity, efficacy and proper selection of patients for induction therapy, particularly induction chemoradiotherapy, will be assessed in ongoing and future clinical trials. PMID- 17335294 TI - Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma. AB - Antibody-based therapeutic approaches have had a significant impact in the treatment of non-Hodgkin's lymphoma (NHL). Rituximab's development as an anti CD20 antibody heralded a new era in treatment approaches for NHL. While rituximab was first shown to be effective in the treatment of relapsed follicular lymphoma, it is now standard monotherapy for front-line treatment of follicular lymphoma, and is also used in conjunction with chemotherapy for other indolent, intermediate and aggressive B-cell lymphomas. The development of rituximab has led to intense interest in this type of therapeutic approach and to development and approval of the radioimmunoconjugates of rituximab, (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, which have added to the repertoire of treatments for relapsed follicular lymphoma and increased interest in developing other conjugated antibodies. Since rituximab is a chimeric antibody, there is a need to develop fully humanised antibodies, such as IMMU-106 (hA20), in order to minimise infusion reactions and eliminate the development of human antibodies against the drug. Further clinical evaluation of antibodies has been based largely on our knowledge of antigen expression on the surface of lymphoma cells and has led to the development of antibodies against CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD52 (alemtuzumab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab]), and CD40 (SGN-40). Furthermore, the VEGF (vascular endothelial growth factor) inhibitor bevacizumab, which was first approved for the treatment of colon cancer is currently under investigation in NHL, and agonists rather than antibodies to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) [rApo2L/TRAIL, HGS-ETR1{mapatumumab}, HGS-ETR2] are currently being investigated as treatments for both advanced solid tumours and NHL. Knowledge of the ability of cancer cells to become resistant to a targeted therapy by activating an alternative pathway to evade apoptosis has driven studies that combine antibodies such as epratuzumab plus rituximab (ER) or ER plus chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) [ER-CHOP], inotuzumab ozogamicin plus rituximab, alemtuzumab plus CHOP (CHOP-C), bevacizumab plus rituximab, and now the combination of rApo2L/TRAIL plus rituximab. As a result of the expansion of research in this area, several treatment-specific adverse effects have been noted, including infusion-related reactions for rituximab, myelosuppression secondary to (90)Y-ibritumomab tiuxetan and (131)I tositumomab, and immunosuppression leading to infectious complications for alemtuzumab. Also, soluble forms of the antigens (sCD30) are now being investigated as potential mechanisms of resistance to antibody treatments by binding the antibody before the drug can bind to the lymphoma cell. In addition, it has also become apparent that these antibodies often have a dose-dependent half-life (rituximab) or long half-lives of up to 2-3 weeks (epratuzumab and galiximab) with a consequent delay to a response, thus influencing how long we should wait for a response before declaring an antibody to be ineffective. Antibody-based therapeutic approaches have already had a profound impact on the treatment of NHL, and it is almost certain that, as their clinical development progresses, we will continue to refine the optimum methods of incorporating these drugs in NHL treatment in order to offer our patients the best clinical benefits. PMID- 17335295 TI - The epidemiology, pathogenesis and treatment of Pseudomonas aeruginosa infections. AB - Pseudomonas aeruginosa is an important bacterial pathogen, particularly as a cause of infections in hospitalised patients, immunocompromised hosts and patients with cystic fibrosis. Surveillance of nosocomial P. aeruginosa infections has revealed trends of increasing antimicrobial resistance, including carbapenem resistance and multidrug resistance. Mechanisms of antimicrobial resistance include multidrug efflux pumps, ss-lactamases and downregulation of outer membrane porins. Mechanisms of virulence include secreted toxins and the ability to form biofilms. The effective treatment of infections caused by P. aeruginosa includes prevention when possible, source control measures as necessary and prompt administration of appropriate antibacterial agents. Antibacterial de-escalation should be pursued in patients with an appropriate clinical response, especially when antibacterial susceptibilities are known. Multidrug-resistant P. aeruginosa may require treatment with less commonly used antibacterials (e.g. colistin), but newer anti-pseudomonal antibacterials are expected to be available in the near future. PMID- 17335297 TI - Antianginal efficacy and safety of ivabradine compared with amlodipine in patients with stable effort angina pectoris: a 3-month randomised, double-blind, multicentre, noninferiority trial. AB - BACKGROUND AND OBJECTIVE: Current medical therapies for the symptoms of angina pectoris aim to improve oxygen supply and reduce oxygen demand in the myocardium. Not all patients respond to current antianginal monotherapy, or even combination therapy, and a new class of antianginal drug that complements existing therapies would be useful. This study was undertaken to compare the antianginal and anti ischaemic effects of the novel heart-rate-lowering agent ivabradine and of the calcium channel antagonist amlodipine. PATIENTS AND METHODS: Patients with a >/=3 month history of chronic, stable effort-induced angina were randomised to receive ivabradine 7.5mg (n = 400) or 10mg (n = 391) twice daily or amlodipine 10mg once daily (n = 404) for a 3-month, double-blind period. Bicycle exercise tolerance tests were performed at baseline and monthly intervals. The primary efficacy criterion was the change from baseline in total exercise duration after 3 months of treatment. Secondary efficacy criteria included changes in time to angina onset and time to 1mm ST-segment depression, rate-pressure product at trough drug activity, as well as short-acting nitrate use and anginal attack frequency (as recorded in patient diaries). RESULTS: At 3 months, total exercise duration was improved by 27.6 +/- 91.7, 21.7 +/- 94.5 and 31.2 +/- 92.0 seconds with ivabradine 7.5 and 10mg and amlodipine, respectively, both ivabradine groups were comparable to amlodipine (p-value for noninferiority < 0.001). Similar results were observed for time to angina onset and time to 1mm ST-segment depression. Heart rate decreased significantly by 11-13 beats/min at rest and by 12-15 beats/min at peak of exercise with ivabradine but not amlodipine, and rate pressure product decreased more with ivabradine than amlodipine (p-value vs amlodipine <0.001, at rest and at peak of exercise). Anginal attack frequency and short-acting nitrate use decreased substantially in all treatment groups with no significant difference between treatment groups. The most frequent adverse events were visual symptoms and sinus bradycardia with ivabradine (0.8% and 0.4% withdrawals, respectively) and peripheral oedema with amlodipine (1.5% withdrawals). CONCLUSIONS: In patients with stable angina, ivabradine has comparable efficacy to amlodipine in improving exercise tolerance, a superior effect on the reduction of rate-pressure product (a surrogate marker of myocardial oxygen consumption) and similar safety. PMID- 17335296 TI - Use of sirolimus in solid organ transplantation. AB - Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor that inhibits cell cycle progression and has proven to be a potent immunosuppressive agent for use in solid organ transplant recipients. The drug was initially studied as an adjunct to ciclosporin (cyclosporine) to prevent acute rejection in kidney transplant recipients. Subsequent studies have shown efficacy when combined with a variety of other immunosuppressive agents. The most common adverse effects of sirolimus are hyperlipidaemia and myelosuppression. The drug has unique antiatherogenic and antineoplastic properties, and may promote immunological tolerance and reduce the incidence of chronic allograft nephropathy. Although sirolimus is relatively non-nephrotoxic when administered as monotherapy, it pharmacodynamically enhances the toxicity of calcineurin inhibitors. Ironically, the drug has been used to facilitate calcineurin inhibitor-free protocols designed to preserve renal function after solid organ transplantation. Whether sirolimus can be used safely over the long term with low doses of calcineurin inhibitors requires further study. The use of sirolimus as a corticosteroid sparing agent also remains to be proven in controlled trials. Postmarketing studies have revealed a number of unforeseen adverse effects including impaired wound healing and possibly proteinuria, oedema, pneumonitis and thrombotic microangiopathy. Overall, sirolimus is a powerful agent when used judiciously with other available immunosuppressants. As is true for all immunosuppressive drugs available for treatment of solid organ transplant recipients, the efficacy of the drug must be balanced against its considerable adverse effects. PMID- 17335299 TI - Agalsidase Beta: a review of its use in the management of Fabry disease. AB - Agalsidase beta (Fabrazyme) is a recombinant human alpha-galactosidase A enzyme approved for intravenous use in the treatment of Fabry disease. Fabry disease is a progressive, multisystemic, potentially life threatening disorder caused by a deficiency of alpha-galactosidase A. This deficiency results in accumulation of glycosphingolipids, particularly globotriaosylceramide (GL-3), in the lysosomes of various tissues. This accumulation is the underlying driver of disease progression. Agalsidase beta provides an exogenous source of alpha-galactosidase A.Intravenous agalsidase beta is effective and well tolerated in patients with Fabry disease. In a phase III trial, agalsidase beta was shown to clear GL-3 from various target cells and, in a subsequent extension of this trial, prevent GL-3 reaccumulation. In a post-approval trial, agalsidase beta was shown to provide significant clinical benefit by reducing the risk of a major clinical event. Thus, agalsidase beta represents an important advance in the treatment of Fabry disease, and agalsidase beta therapy should be strongly considered in patients with Fabry disease who are suitable candidates. PMID- 17335298 TI - Insulin lispro: a review of its use in the management of diabetes mellitus. AB - Insulin lispro, alone (Humalog) or as premixture (Humalog Mix25 or Humalog Mix50) is indicated for the treatment of hyperglycaemia in diabetes mellitus in many countries worldwide. It is a recombinant human insulin analogue and, except for the transposition of two amino acids, is identical to endogenous human insulin. Insulin lispro has a faster onset of action and shorter duration of activity than regular human insulin, and the time-action profile of insulin lispro mimics that of the physiological response of endogenous human insulin to food intake. In diabetic patients, from young children to the elderly, it has demonstrated postprandial blood glucose control similar to or better than that achieved with regular human insulin, without an increased risk of hypoglycaemia. In some trials, the risk of hypoglycaemia, including nocturnal episodes, was less in insulin lispro recipients than in regular human insulin recipients. Insulin lispro alone, or as a premixture with the longer-acting insulin neutral protamine lispro, can be administered immediately before or after meals. This convenient and flexible injection schedule may enable patients, including those with a non routine lifestyle or unpredictable eating or exercising habits, to achieve the tight glycaemic control required to minimise long-term complications of diabetes and contributes to patient satisfaction with treatment. PMID- 17335300 TI - Rupatadine: a review of its use in the management of allergic disorders. AB - Rupatadine (Rupafin, Rinialer, Rupax, Alergoliber) is a selective oral histamine H(1)-receptor antagonist that has also been shown to have platelet-activating factor (PAF) antagonist activity in vitro. It is indicated for use in seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR) and chronic idiopathic urticaria (CIU) in patients aged >/=12 years. Clinical trials show that rupatadine is an effective and generally well tolerated treatment for allergic rhinitis and CIU. It has a rapid onset of action and a prolonged duration of activity. Importantly, it has no significant effect on cognition, psychomotor function or the cardiovascular system. Once-daily rupatadine significantly improves allergic rhinitis symptoms in patients with SAR, PAR or persistent allergic rhinitis (PER) compared with placebo, and provides similar symptom control to that of loratadine, desloratadine, cetirizine or ebastine. In patients with CIU, longer-term use of rupatadine improves CIU symptoms to a greater extent than placebo. It is as well tolerated as other commonly used second-generation H(1)-receptor antagonists. Thus, the introduction of rupatadine extends the range of oral agents available for the treatment of allergic disorders, including allergic rhinitis and CIU. PMID- 17335301 TI - Sorafenib: in advanced renal cancer. AB - black triangle Sorafenib is an oral multikinase inhibitor that targets the mitogen-activated protein kinase signalling pathway and receptor tyrosine kinases involved in tumour proliferation and angiogenesis.black triangle In the large, phase III, randomised, double-blind, multicentre Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) of patients with advanced clear-cell renal cell cancer in whom previous systemic therapy had failed, median progression-free survival was doubled in patients receiving sorafenib compared with those receiving placebo (5.9 vs 2.8mo).black triangle Significantly more patients receiving sorafenib than those receiving placebo in the phase III trial experienced complete or partial responses or stable disease.black triangle Age, risk-assessment score, prior treatment, metastasis in lung or liver, or time from diagnosis did not affect the improved progression-free survival in sorafenib recipients.black triangle In a randomised, phase II discontinuation trial of patients with advanced renal cancer, in which only those showing stable disease with sorafenib were randomised to further sorafenib or placebo, more patients receiving sorafenib were free of progressive disease 12 weeks after randomisation than were those receiving placebo, and median progression-free survival was longer in sorafenib recipients.black triangle In clinical trials, most drug related adverse events were mild to moderate in severity. Grade 3/4 hand-foot skin reaction and hypertension occurred more often with sorafenib than with placebo. PMID- 17335304 TI - Economic evaluation and decision making: reimbursing trastuzumab in early-stage breast cancer. PMID- 17335305 TI - Economic evaluations of cholesterol-lowering drugs: a critical and systematic review. AB - The wide availability of economic evaluations and their increasing importance for decision making emphasises the need for economic evaluations that are methodologically sound. The aim of this review was to provide users of economic evaluations of cholesterol-lowering drugs with an insight into the quality of these evaluations. By focusing on the most relevant studies, the gap between research and policy making may be narrowed. A systematic review was conducted. All Dutch and English publications on economic evaluations of cholesterol lowering drugs were identified by searching PubMed, the Centre for Reviews and Dissemination database (CRD), the NHS Economic Evaluation Database (NHS EED), the Health Technology Assessment database (HTA) and the Database of Abstracts of Reviews of Effects (DARE). A search strategy was set up to identify the articles to be included. The quality of these articles was assessed using Drummond's checklists. The scoring was performed by at least two reviewers. When necessary, disagreement between these reviewers was decided upon in a consensus meeting. We calculated an average quality score for the included articles. The search identified 1390 articles, of which 23 were included. Most studies measured the costs per life-year gained. The overall score per study was disappointing and varied between 2.7 and 7.7, with an average of 5.5. Most studies scored high on the measurement of costs and consequences, whereas the establishment of effectiveness left room for improvement. Only two studies included a well performed incremental analysis. This study noted an increase of quality of economic evaluations over time, suggesting the value of cost-effectiveness studies for policy decisions increases over time. In general, piggy-back evaluations tended to score higher on quality and may therefore be more valuable in decision making. PMID- 17335306 TI - Enzyme replacement therapy in orphan and ultra-orphan diseases: the limitations of standard economic metrics as exemplified by Fabry-Anderson disease. AB - BACKGROUND: Fabry-Anderson disease is an x-linked deficiency of lysosomal alpha galactosidase A (GALA), resulting in chronic renal failure, cardiac arrhythmia, hypertrophy, valvular disease, pain (acro-paraesthesiae) and stroke, together with premature mortality. The disease has a significant impact on quality of life (QOL), as illustrated by studies using the EQ-5D. A specific treatment is available for Fabry-Anderson disease consisting of intravenous enzyme replacement therapy (ERT) of the deficient enzyme. The variable clinical efficacy and cost of ERT has resulted in reluctance by some health providers to approve it. METHODS: We use the limited QOL data available in the Fabry-Anderson disease literature on ERT to derive standard economic metrics. These were derived by bootstrap estimates of the incremental net benefit (INB) statistics together with a cost effectiveness acceptability curve relating the willingness to pay to the probability that the INB was >0. The estimates were further developed by adoption of a supplementary Bayesian approach utilising a sceptical and enthusiastic prior of the INB of ERT in Fabry-Anderson disease. RESULTS: ERT for Fabry-Anderson disease is not economically viable by standard health programme evaluation metrics. Based on current ERT costs (year 2005 values), derivation of the INB distribution, and a Bayesian analysis using an enthusiastic and sceptical prior of the INB, an upper (350,000 dollars over 1 year) and lower (175,000 dollars over 1 year) economic cost, respectively, of ERT was derived. CONCLUSION: The cost of ERT will always result in a net deficit to society under current costing and ERT efficacy as determined by the QALY metric. The rules of fair cooperation should govern decision making both for ERT in Fabry-Anderson disease and for funding therapeutic advances in other rare diseases belonging to the orphan and ultra-orphan categories. PMID- 17335307 TI - Do drugs reduce utilisation of other healthcare resources? AB - BACKGROUND: Drug expenditures per capita have drastically increased over the last quarter century in Canada, with a share of overall healthcare costs rising from 8.8% in 1980 to 16.8% in 2002. Pressure to curb expenditure on drugs has increased accordingly, but containing drug expenditure might increase costs elsewhere in the healthcare sector. OBJECTIVE: To measure substitution patterns between drugs and other healthcare resources over the last 25 years and thus assess whether containing drug costs might result in higher expenditure elsewhere in the healthcare system. METHODS AND DATA: A production function approach was used, in which life expectancy was modelled as a function of per capita drugs and non-drug healthcare resources, among other factors. Estimates are used to calculate a marginal rate of substitution, or trade-off, between drugs and non drug healthcare resources, for a given level of life expectancy in the population. The model is estimated from a societal perspective, with panel data techniques using Canadian provincial-level data on health expenditure and spending on physicians per capita for the period 1980-2002, as well as individual survey data on lifestyle habits such as cigarette consumption and body mass index. RESULT: Using life expectancy at birth for males as the production function, increasing drug spending by Can 1.00 dollars (constant 2003 values) was accompanied by a decrease of Can 1.48 dollars in non-drug, non-physician healthcare resources over the study period, without affecting life expectancy at birth. Results using life expectancy at birth for females as the production function showed a decrease of Can 1.05 dollars in non-drug, non-physician healthcare resources over the same period. CONCLUSION: Using life expectancy as a general health indicator, results suggest that increases in drug spending could be more than offset by decreases in other healthcare spending without affecting the health of the population. This suggests that better access to drugs may be an effective strategy to decrease overall healthcare costs. Freeing up healthcare dollars by reallocating spending towards drugs could provide opportunities for overall healthcare cost savings without negatively impacting the health of the population. PMID- 17335308 TI - Recombinant erythropoietin for chemotherapy-related anaemia: economic value and health-related quality-of-life assessment using direct utility elicitation and discrete choice experiment methods. AB - OBJECTIVE: To assess both the health-related quality of life (HR-QOL) and the economic value of erythropoietin treatment in chemotherapy-related anaemia using direct utility elicitation and discrete choice experiment (DCE) methods from a societal perspective in the UK. METHODS: The time trade-off (TTO) method was employed to obtain utility values suitable for the calculation of QALYs for no, mild, moderate and severe anaemia. Health-state descriptions were developed using the Functional Assessment of Cancer Therapy - Anaemia (FACT-AN) subscale and the EQ-5D questionnaires, and were validated by clinical experts and patients. In addition, a DCE was implemented to elicit preferences for various anaemia treatment scenarios. The DCE analysis comprised important aspects of treatment identified from a literature review and by consultation with expert clinicians and cancer patients. The DCE included cost as an attribute in order to elicit willingness-to-pay (WTP) values (pound, 2004 values). The two methods were applied in the same cross-sectional sample of 110 lay people. Face-to-face interviews were conducted between February and March 2004. RESULTS: The mean utility scores were 0.86 (standard error [SE] 0.014) for the no-anaemia state, and 0.78 (SE 0.016), 0.61 (SE 0.020) and 0.48 (SE 0.020) for the mild, moderate and severe anaemia states, respectively. The DCE results revealed the following preferences as significant predictors of choice: higher level of relief from fatigue, lower duration of administration, subcutaneous/intravenous administration versus cannula injection, GP versus hospital location, lower risk of infection or allergic reactions and lower cost per month to the patient. Attribute levels were valued higher for recombinant erythropoietin than for blood transfusion; this is reflected in an incremental welfare value of 368 pounds (95% CI 318, 419). CONCLUSIONS: The results highlight a societal view that the severity of chemotherapy-related anaemia will significantly affect cancer patients' HR-QOL. The DCE survey shows that the public value favourably the attributes of treatment with recombinant erythropoietin, and indicates a likely patient preference for treatment with recombinant erythropoietin over blood transfusion. PMID- 17335309 TI - Cost effectiveness of an adherence-improving programme in hypertensive patients. AB - BACKGROUND: Non-adherence to antihypertensive drugs is high, and the economic consequences of non-adherence may be substantial. The Medication Events Monitoring System (MEMS), which is a method to improve adherence, has been shown to be a useful tool for the management of adherence problems. OBJECTIVE: To assess the cost effectiveness of the MEMS compared with usual care in a population of hypertensive patients with poor adherence. The MEMS programme consisted of provision of containers fitted with electronic caps together with adherence training if indicated. METHODS: In a randomised controlled trial, 164 hypertensive patients in the experimental strategy and 89 patients in the usual care strategy were followed for 5 months. Patients who had a systolic blood pressure (SBP) > or = 160 mm Hg and/or diastolic BP (DBP) > or = 95 mm Hg despite the use of antihypertensive drugs were eligible. Patients were recruited by a GP, and treatment took place in general practice. In the experimental strategy, electronic monitoring of the intake of antihypertensive drugs was introduced without change of medication. Unsatisfactory adherence was defined as < 85% of days with the number of doses taken as prescribed. In the usual care strategy, antihypertensive treatment was intensified by the addition or change of antihypertensive drugs, if necessary, without provision of an electronic monitor. Outcome parameters included the proportion of patients with normalised blood pressure (NBP) at 5 months and QALYs. Costs were quantified from the healthcare and societal perspective. Non-parametric bootstrap simulations were performed to quantify the uncertainty around the mean estimates and cost-effectiveness acceptability curves were presented. In addition, a number of univariate sensitivity analyses were performed on deterministic variables. RESULTS: At 5 months, 3.1% (95% UI [uncertainty interval] -9.7%, +15.8%) more patients had NBP, and 0.003 (95% UI -0.005, +0.010) more QALYs were generated in the experimental strategy. A statistically significant lower percentage of patients had a dose escalation in the experimental strategy. Irrespective of the ceiling ratio for cost effectiveness, the cost-effectiveness probability was between 75% and 80% for the analysis from the healthcare perspective using proportion of patients with NBP as the outcome parameter. For the analysis from the societal perspective using QALYs as the outcome parameter, this probability was between 45% and 51%. CONCLUSION: For a time horizon of 5 months, a difference in both cost and effect could not be detected between an adherence-improving programme compared with usual care for hypertensive patients. The probability that the adherence improving programme is cost effective is at best moderate. Moreover, the cost effectiveness result is surrounded with considerable uncertainty and large-scale implementation warrants additional research into the economic consequences of this intervention. Patients may benefit from the use of a MEMS monitor in situations where BP targets are not reached because of suspected non-adherence and both patient and GP are reluctant to increase the dose or number of antihypertensive drugs. PMID- 17335310 TI - Modelling cost effectiveness of insulin glargine for the treatment of type 1 and 2 diabetes in Canada. AB - BACKGROUND AND OBJECTIVE: Intensive insulin therapy improves glycosylated haemoglobin (Hb(A1C)) levels and delays the onset of long-term diabetes-related complications. Current treatment guidelines recommend maintaining a glycosylated haemoglobin (Hb(A1C)) of < or = 7% in patients with type 1 and 2 diabetes mellitus. However, the risk of hypoglycaemia increases with lower Hb(A1C) levels. As such, patients often choose to settle for suboptimal glucose control in order to prevent hypoglycaemic events. At a given Hb(A1C) level, treatment with insulin glargine results in a lower risk of hypoglycaemia in type 1 and 2 diabetes compared with NPH insulin. It has been proposed that the lower hypoglycaemic risk will allow more patients to achieve target Hb(A1C) levels with insulin glargine compared with NPH insulin. The objective of this study was to assess the cost effectiveness of insulin glargine compared with NPH insulin in patients with type 1 or 2 diabetes who had inadequate glycaemic control. METHODS: A long-term, state transition model was developed to simulate the natural history of type 1 and 2 diabetes. Risks of diabetes-related macro- and microvascular complications and mortality by Hb(A1C) levels were estimated based on the UKPDS (United Kingdom Prospective Diabetes Study). Outcome measures included complication rates and associated costs, insulin costs, life years (LYs) and QALYs. The baseline analysis was conducted for patients with type 1 and 2 diabetes (aged 27 and 53 years, respectively) with Hb(A1C) levels >7%, using a 36-year time horizon and a Canadian public payer perspective. Costs and effects were discounted at 5% per annum. Univariate sensitivity analyses were performed on key model inputs. All costs were reported in $Can (2005 values). RESULTS: The NPH insulin group had lower total costs than the insulin glargine group for patients with inadequately controlled diabetes (Hb(A1C) >7%; lifetime difference 1398 Can dollars and 1992 Can dollars, respectively, in type 1 and 2 diabetes). However, patients treated with insulin glargine had greater total and quality-adjusted life expectancy than those who received NPH insulin (incremental LY = 0.08 and QALYs = 0.07 in type 1 diabetes and incremental LY = 0.25 and QALYs = 0.23 in type 2 diabetes). The weighted incremental cost per LY gained and QALY gained were 18,661 Can dollars and 20,799 Can dollars, respectively, in type 1 diabetes and 8041 Can dollars and 8618 Can dollars, respectively, in type 2 diabetes (discounted results). CONCLUSIONS: The cost-effectiveness ratios for insulin glargine use for type 1 and 2 diabetes provide evidence for its adoption from a Canadian healthcare payer perspective. PMID- 17335311 TI - A history of the concept of atypical depression. AB - Atypical depression is defined as a type of depression that responds preferentially to monoamine oxidase inhibitors. In addition to mood reactivity, symptoms of atypical depression include hypersomnia, hyperphagia or weight gain, leaden paralysis, and a long-standing pattern of rejection sensitivity or interpersonal sensitivity. Over the years, atypical depression has been associated with or identified as nonendogenous depression, anxiety, reverse vegetative shift, chronic pain, bipolar disorder, and rejection sensitivity. This presentation discusses the history of the identification of atypical depression, starting with its initial identification in 1959, and describes the important studies of atypical depression and its treatment by various research groups during the past 50 years. The presentation concludes by differentiating between typical and atypical depression and detailing of some of the clinical characteristics of atypical depression. PMID- 17335312 TI - Effectiveness of antipsychotic drugs in patients with chronic schizophrenia: efficacy, safety and cost outcomes of CATIE and other trials. AB - After the introduction of clozapine in 1990, second-generation-or atypical antipsychotics were thought to be more effective, safer, and less costly than first-generation-or typical-antipsychotics. However, only limited evidence on the efficacy and safety of atypicals was available. Because of this knowledge gap, the National Institute of Mental Health sponsored the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) to compare first- and second generation antipsychotics. The CATIE trial found that antipsychotic drug treatments are generally effective overall but have various limitations as reflected by high rates of discontinuation due to both efficacy and tolerability problems. In addition, the trial found that conventional agents with intermediate potency were comparably effective with atypical agents. PMID- 17335313 TI - Cost-effectiveness measures, methods, and policy implications from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) for schizophrenia. AB - Sales of atypical antipsychotics have expanded rapidly as their use for treatment of schizophrenia and other illnesses has increased. The CATIE trial was designed to evaluate the cost-effectiveness of these medications. Cost-effectiveness analysis in CATIE examined the benefits and costs of treatments and attempted to determine whether one treatment would result in better outcomes and lower costs than another one. While the data from CATIE on cost-effectiveness have not been analyzed yet, it is still possible to consider the potential implications of the analysis, including how the roles of researchers and stakeholders should be considered in deciding optimal clinical practices and public policies. PMID- 17335314 TI - The art (and blood sport) of psychopharmacology research: who has a dog in the fight? PMID- 17335315 TI - Longitudinal effects of personality disorders on psychosocial functioning of patients with major depressive disorder. AB - OBJECTIVE: No previous research has focused on psychosocial functioning in understanding how personality disorders compound the impairment caused by major depressive disorder over time. This report describes the effects of persistent and remitting comorbid personality disorders on the depressive status and functioning of patients with major depressive disorder over the course of 2 years. METHOD: Longitudinal data on functioning from the first 2 years of the Collaborative Longitudinal Personality Disorders Study were evaluated for 3 groups of subjects with major depressive disorder: subjects with major depressive disorder alone (N = 103), those with persistent comorbid personality disorders (N = 164), and those with comorbid personality disorders that remitted (N = 69). DSM IV criteria were used for mood and personality disorder diagnoses. The data were gathered from September 1996 to August 2000 and from September 2001 to September 2004. RESULTS: Subjects whose personality disorders remitted were more likely than those with persisting personality disorders to have major depressive disorder remit. Social functioning, as measured by the Longitudinal Interval Follow-up Evaluation and the Global Assessment of Functioning, improved across a range of domains over time, with most gains occurring in the first 6 months of follow-up and with differential improvement by group. As hypothesized, subjects whose personality disorders remitted fared nearly as well as did subjects without personality disorders, whereas subjects whose personality disorders persisted functioned most poorly. CONCLUSIONS: Outcome research on major depressive disorder has often ignored Axis II disorders. Our data indicate that the longitudinal course of personality psychopathology meaningfully influences depressive outcome and psychosocial functioning in patients with major depressive disorder. The findings indicate the need to target both symptom relief and psychosocial functioning and to treat both personality and mood disorders in comorbid patients. PMID- 17335316 TI - Persisting low use of antipsychotics in the treatment of major depressive disorder with psychotic features. AB - OBJECTIVE: Practice guidelines recommend the use of a combination of an antidepressant and an antipsychotic for the pharmacologic treatment of major depressive disorder with psychotic features (MD-Psy). We assessed the extent to which the pharmacotherapy received by patients with MD-Psy under usual care conforms to these recommendations. METHOD: We assessed the pharmacotherapy received under usual care conditions by 100 patients with MD-Psy prior to enrollment in STOP-PD (Study of the Pharmacotherapy of Psychotic Depression), a 12-week randomized, controlled trial comparing olanzapine plus sertraline to olanzapine plus placebo. Our assessment took place from January 2003 to May 2004. The strength of antidepressant trials was rated using the Antidepressant Treatment History Form (ATHF). The strength of antipsychotic trials or combinations of antidepressants and antipsychotics was rated using a modified version of the ATHF. We also determined whether the strength of antipsychotic or combination trials was associated with age, the duration of the current depressive episode, medical burden, cognitive status, or the severity of depressive or psychotic symptoms. RESULTS: Most patients with MD-Psy were treated with antidepressants (N = 82, 82%) or antipsychotics (N = 65, 65%). About half of the patients (N = 48, 48%) received therapeutic doses of an antidepressant; 10% (N = 10) received an intermediate dose of an antipsychotic, and 6% (N = 6) received a high dose. Overall, only 5% (N = 5) received a combination of an adequate dose of an antidepressant and a high dose of an antipsychotic. The strength of both antipsychotic trials (p = .021) and combination trials (p = .039) was significantly associated only with a longer duration of the current depressive episode. CONCLUSIONS: These findings show a persisting low use of antipsychotics in the treatment of MD-Psy. Given the high morbidity rates associated with MD-Psy, it is important to continue to educate clinicians regarding its identification and treatment. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00056472. PMID- 17335318 TI - Health-related quality of life in euthymic bipolar disorder patients: differences between bipolar I and II subtypes. AB - OBJECTIVE: The aim of the present study was to compare health-related quality of life (HRQoL) measures in euthymic patients with bipolar I and II disorder. We included as comparison samples a group of subjects with recurrent major depression (RMD) and a group of non-psychiatrically ill individuals. METHOD: HRQoL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) in 253 subjects recruited in 5 Italian centers: 90 patients with bipolar I disorder, 52 patients with bipolar II disorder, 61 subjects with RMD, and 50 healthy comparison individuals. All subjects were evaluated with the Structured Clinical Interview for DSM-IV; psychiatric patients had to be in a euthymic state for at least 2 months prior to the inclusion in the study, as confirmed by a Hamilton Rating Scale for Depression total score < 8 and a Young Mania Rating Scale total score < 6. Data were drawn from a study that was performed from May 2003 to December 2004. RESULTS: When we compared the bipolar and RMD groups with the control group of non-psychiatrically ill individuals and controlled for differences in mean actual age, both bipolar subgroups and subjects with RMD had lower SF-36 mean scores on several subscales; differences in mean SF-36 scores were also detected between bipolar subtypes: bipolar II patients showed HRQoL that was poorer than that of bipolar I patients, even after controlling for age, age at onset, and length of illness, and equal to that of RMD subjects. CONCLUSION: Our study provides evidence that bipolar type II is associated with poorer HRQoL compared to type I even during sustained periods of euthymia and excluding residual symptoms. Interventions targeting rehabilitation and/or functional enhancement may be helpful to improve HRQoL, especially among patients with bipolar II disorder. PMID- 17335317 TI - Efficacy and safety of topiramate monotherapy in civilian posttraumatic stress disorder: a randomized, double-blind, placebo-controlled study. AB - OBJECTIVE: This double-blind, placebo-controlled trial assessed efficacy and safety of topiramate monotherapy in civilian posttraumatic stress disorder (PTSD). METHOD: Outpatients (18-64 years) with DSM-IV non-combat-related PTSD and Clinician-Administered PTSD Scale (CAPS) scores >or= 50 were eligible. Topiramate was started at 25 mg/day and titrated by 25-50 mg/week to 400 mg/day or maximum tolerated dose. Data were collected between April 26, 2002, and February 4, 2004. Primary efficacy, change in total CAPS score, and secondary efficacy measures were assessed by analysis of covariance in the intent-to-treat (ITT) population with last observation carried forward. RESULTS: The ITT population comprised 38 patients with mean +/- SD baseline total CAPS scores of 88.3 +/- 13.8 (topiramate, N = 19) and 91.1 +/- 13.7 (placebo, N = 19). Although a decrease in total CAPS score was noted (topiramate, -52.7; placebo, -42.0), this difference was not statistically significant (p = .232). Topiramate-treated patients exhibited significant reductions in reexperiencing symptoms (CAPS cluster B: topiramate, 74.9%; placebo, 50.2%; p = .038) and Treatment Outcome PTSD scale (topiramate, 68.0%; placebo, 41.6%; p = .025). Reductions approaching statistical significance, based on a nominal p value, were noted in mean total Clinical Global Impressions-Improvement Scale scores (topiramate, 1.9 +/- 1.2; placebo, 2.6 +/- 1.1; p = .055). CONCLUSION: These preliminary results suggest that further, adequately powered studies of topiramate for the treatment of civilian PTSD are warranted. PMID- 17335319 TI - Aripiprazole for treatment-resistant schizophrenia: results of a multicenter, randomized, double-blind, comparison study versus perphenazine. AB - OBJECTIVE: Treatment-resistant schizophrenia poses a major therapeutic challenge. This multicenter, double-blind, randomized study compared the efficacy and safety of aripiprazole and perphenazine in treatment-resistant patients with schizophrenia. METHOD: Schizophrenia patients (DSM-IV diagnosis) with a history of antipsychotic resistance underwent 4 to 6 weeks of open-label treatment with olanzapine or risperidone to confirm treatment resistance. Only patients who completed this open-label period and failed to respond (< 20% improvement in Positive and Negative Syndrome Scale [PANSS] total score or a Clinical Global Impressions-Severity of Illness score >or= 4) entered the 6-week, double-blind treatment phase. In all, 300 patients with confirmed treatment resistance were randomly assigned to aripiprazole (15-30 mg/day) or perphenazine (8-64 mg/day). The primary outcome measure was change in PANSS score from baseline. The study was conducted between August 30, 2000, and March 18, 2002. RESULTS: Both aripiprazole and perphenazine treatment were associated with clinically relevant improvements in PANSS total scores from baseline. After 6 weeks, 27% of aripiprazole-treated patients and 25% of perphenazine-treated patients were responders (>or= 30% decrease in PANSS total score or a Clinical Global Impressions-Improvement score of 1 or 2). Perphenazine-treated patients had a higher incidence of extrapyramidal symptom-related adverse events, mean increases (i.e., worsening) in extrapyramidal symptom rating scale scores, and a higher rate of elevated prolactin levels than aripiprazole (57.7% vs. 4.4%, p < .001). Improvements in quality of life considered to be clinically relevant (>or= 20% improvement in Quality of Life Scale score) occurred in 36% of the aripiprazole treated patients and in 21% of those treated with perphenazine (p = .052). CONCLUSIONS: Aripiprazole and perphenazine, at the doses used here, can improve the symptoms of schizophrenia in treatment-resistant patients who have failed to respond to olanzapine or risperidone. PMID- 17335320 TI - A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. AB - OBJECTIVE: Two parallel, 8-week double-blind studies compared olanzapine/fluoxetine combination, olanzapine, and fluoxetine in outpatients with treatment-resistant depression (TRD). METHOD: Treatment-resistant depression was defined as a documented history of current-episode antidepressant failure plus a prospective failure on fluoxetine. Following an 8-week fluoxetine lead-in, 605 nonresponders with DSM-IV major depressive disorder were randomly assigned to olanzapine/fluoxetine combination, olanzapine, or fluoxetine. The primary outcome measure was baseline-to-endpoint mean change on the Montgomery-Asberg Depression Rating Scale (MADRS). The study was conducted from April 2002 to May 2005. RESULTS: After 8 weeks of double-blind treatment, Study 1 revealed no statistically significant therapy differences in MADRS mean change (olanzapine/fluoxetine combination: -11.0, fluoxetine: -9.4, olanzapine: -10.5). In Study 2, olanzapine/fluoxetine combination demonstrated significantly greater MADRS improvement (-14.5) than fluoxetine (-8.6, p < .001) and olanzapine (-7.0, p < .001). Pooled study results revealed significant differences for olanzapine/ fluoxetine combination (-12.7) versus fluoxetine (-9.0, p < .001) and olanzapine (-8.8, p < .001). Pooled remission rates were 27% for olanzapine/ fluoxetine combination, 17% for fluoxetine, and 15% for olanzapine. Adverse events were consistent with previous studies. Cholesterol mean change (mg/dL) was +15.1 for olanzapine/ fluoxetine combination, +0.8 for fluoxetine, and +2.7 for olanzapine. Mean weight change (kg) was +4.9 for olanzapine/fluoxetine combination, +0.4 for fluoxetine, and +5.5 for olanzapine. Nonfasting glucose mean change (mg/dL) was +11.4 for olanzapine/fluoxetine combination, +4.9 for fluoxetine, and +9.9 for olanzapine. CONCLUSION: Patients with TRD (defined as treatment failure on 2 antidepressants) taking olanzapine/fluoxetine combination demonstrated significantly greater improvement in depressive symptoms than patients taking olanzapine or fluoxetine in 1 of 2 studies and in the pooled analysis. When considered within the context of all available evidence, olanzapine/fluoxetine combination is an efficacious therapy for patients with TRD. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00035321. PMID- 17335321 TI - Melatonin in schizophrenic outpatients with insomnia: a double-blind, placebo controlled study. AB - BACKGROUND: Low nighttime levels of melatonin have been demonstrated in patients with insomnia, and melatonin has been shown to have hypnotic properties in some groups of such subjects. Low melatonin levels have also been observed in patients with schizophrenia; however, there is little literature on the efficacy of exogenous melatonin in treating insomnia associated with schizophrenia. METHOD: Stable DSM-IV schizophrenic outpatients (N = 40) with initial insomnia of at least 2 weeks' duration were randomly assigned to augment their current medications with either flexibly dosed melatonin (3-12 mg/night; N = 20) or placebo (N = 20). By use of a questionnaire, double-blind assessments of aspects of sleep functioning were obtained daily across the next 15 days. The study was conducted between March and December 2002. RESULTS: The modal stable dose of melatonin was 3 mg. Relative to placebo, melatonin significantly improved the quality and depth of nighttime sleep, reduced the number of nighttime awakenings, and increased the duration of sleep without producing a morning hangover (p < .05). Subjectively, melatonin also significantly reduced sleep-onset latency, heightened freshness on awakening, improved mood, and improved daytime functioning (p < .05). CONCLUSION: Melatonin may be a useful short-term hypnotic for schizophrenic patients with insomnia. Melatonin could be considered for patients in whom conventional hypnotic drug therapy or higher sedative antipsychotic drug doses may be problematic. PMID- 17335322 TI - Predictors of suicide in first-episode affective and nonaffective psychotic inpatients: five-year follow-up of patients from a catchment area in Vitoria, Spain. AB - OBJECTIVE: To determine the baseline demographic and clinical characteristics associated with suicide attempts over 5 years following a first admission for psychosis and to assess the relationship between suicidal behavior during 5-year follow-up and clinical factors. METHOD: All inpatients consecutively admitted between February 1997 and January 1999 with a first psychotic episode from a specific catchment area in Spain were included at baseline; they were followed up yearly over a 5-year period with an extensive protocol that included the Structured Clinical Interview for DSM-IV, the Positive and Negative Syndrome Scale, and the 21-item Hamilton Rating Scale for Depression. The primary outcome measure was suicide attempts. Comorbidity with alcohol and drug abuse was recorded, as were all suicidal acts made by patients over the follow-up period. Relationships between suicidal outcome and baseline clinical features were examined. Logistic regression modeling was used to test the significance and independence of associations of relevant factors to suicidal status. RESULTS: Of 83 first-episode psychotic patients, 14.5% displayed suicidal behavior within the 5 years following the first admission, and 2.4% died by suicide. Suicide rate was 0.48%/ year and attempt rate was 2.89%/year, with a 1.5-fold (95% CI = 1.07 to 2.22) greater risk for each depressive symptom at index episode and with an 8 fold (95% CI = 1.45 to 44.40) higher risk among patients with baseline stimulant abuse (cocaine and amphetamine). CONCLUSIONS: Patients with a first-episode psychotic disorder seemed to be a high-risk population for suicidal behavior. Depressive symptoms during the index psychotic episode and comorbidity with stimulant abuse at baseline were relevant predictive factors for suicidal behavior during the first years of first affective and nonaffective psychotic episodes. PMID- 17335323 TI - Impact of comorbid attention deficit disorder on the direct medical costs of treating adults with depression in managed care. AB - OBJECTIVE: To assess the impact of comorbid attention deficit disorder (ADD) on the direct medical costs of treating adults with depression in a mixed-model health maintenance organization. METHOD: Annual mean and marginal health care costs were calculated for adults who were continuously enrolled at Group Health Cooperative during 2001 and who were diagnosed with depression, ADD, or both ADD and depression according to ICD-9-CM criteria during 2001. RESULTS: Of 249,874 adults continuously enrolled during 2001, 17,792 (7.1%) were diagnosed with depression, 1023 (0.4%) were diagnosed with ADD, and 454 (0.2%) were diagnosed with both depression and ADD. The mean total annual cost for an adult with a diagnosis of depression in 2001 exceeded that for the average adult enrolled in Group Health by 109% ($6029 vs. $2880). Of the $6029 mean total annual cost for treating an adult with a diagnosis of depression, $1872 (31%) was specifically attributable to depression. The presence of comorbid ADD resulted in ADD- and depression-attributed marginal costs approximately 29% higher than the costs specifically attributed to depression alone ($2418 vs. $1872). In fact, among patients with a diagnosis of ADD and depression, ADD- and depression-attributed costs approached the mean total cost of health care in the sample as a whole ($2880). CONCLUSION: Depression is associated with high direct medical costs. The marginal costs of treating comorbid depression and ADD substantially exceed those of treating depression alone. These results underline the importance of considering the costs of comorbidities in estimating the economic burden of depression and developing cost-effective disease-management strategies. PMID- 17335324 TI - A comparison of rates of residual insomnia symptoms following pharmacotherapy or cognitive-behavioral therapy for major depressive disorder. AB - OBJECTIVE: A number of pharmacologic studies have documented that insomnia is among the most commonly reported residual symptoms after remission from depression. Residual symptoms after remission are particularly relevant because these symptoms confer greater risk for subsequent depression. This study was the first to date to examine residual insomnia after cognitive-behavioral therapy (CBT) for depression and to compare CBT with pharmacotherapy for depression on residual insomnia rates. METHOD: This naturalistic study examined rates of posttreatment insomnia complaints in patients (N = 94) who had been diagnosed with major depressive disorder (MDD), according to DSM-IV criteria, and who remitted from MDD after completing at least 20 weeks of either CBT or pharmacotherapy at an outpatient clinic specializing in mood disorders. Participants were randomly assigned to the treatment conditions, but only the data from those who completed treatment and remitted were analyzed. Primary outcome measure was the 17-item Hamilton Rating Scale for Depression. Data were collected from October 1, 1999, to September 23, 2003. Groups were compared using a chi(2) for nominal data. RESULTS: The rate of posttreatment insomnia was 22% for sleep-onset insomnia, 26% for sleep-maintenance insomnia, and 17% for early morning awakenings, and the rates did not statistically differ across the 2 treatment groups. CONCLUSION: Although CBT and pharmacotherapy effectively addressed depression in these patients and addressed insomnia symptoms for many, there were a number of patients with residual insomnia. Whereas there appears to be no difference between CBT and pharmacotherapy with regard to rates of residual insomnia, the rates of such insomnia remaining after these treatments suggest that adjunctive sleep treatment to specifically address insomnia may be necessary for some MDD patients. PMID- 17335325 TI - Effect of bupropion extended release on negative emotion processing in major depressive disorder: a pilot functional magnetic resonance imaging study. AB - BACKGROUND: Prior imaging studies suggest that patients with major depressive disorder have abnormalities in frontal and limbic neural circuitry including the amygdala, which is relatively more activated at rest and in response to negative emotional stimuli (sadness, fear, etc.) in depressed patients than in controls. Concurrently, patients with depression may have decreased activation of attentional executive regions in response to attentional stimuli. This study examined the effect of bupropion XL, an extended release formulation of the nonserotonergic antidepressant agent bupropion, using a paradigm that investigated both negative emotional response and attentional processing. METHOD: Functional magnetic resonance imaging (fMRI) scans and clinical ratings were obtained for 10 patients with DSM-IV-TR-defined major depressive disorder (mean [SD] age = 41 [+/- 7] years, mean [SD] Hamilton Rating Scale for Depression [HAM D] score = 21 [+/- 4]) before and after 8 weeks of treatment with bupropion XL. The fMRI sessions were conducted during administration of the Emotional Oddball Task; scans were obtained while subjects viewed emotional distracters and performed an attentional executive function task. The primary outcome was fMRI activations evoked by the emotional distracters. The first baseline fMRI scan was performed in December 2004, and the last posttreatment scan was in March 2005. RESULTS: Treatment with bupropion XL was associated with improvements in HAM-D and Clinical Global Impressions scale ratings (p < .05). Treatment reduced fMRI activation during emotional distracters in several regions including right orbital frontal cortex, left dorsomedial prefrontal cortex, right ventromedial prefrontal cortex, right anterior cingulate cortex, right inferior frontal cortex, right amygdala/parahippocampal area, right caudate, right fusiform gyrus, and left posterior cingulate. In addition, changes in fMRI activation in the amygdala correlated with improvements on the HAM-D (p < .05). Treatment increased activation to attentional targets in the following regions: right middle and inferior frontal gyri, right caudate, and bilateral precuneus. CONCLUSION: Despite the limitations of a small sample size and the lack of a placebo control group, this study demonstrated that bupropion XL therapy for 8 weeks may attenuate emotion-induced, blood-oxygen-level-dependent (BOLD) activation responses in the amygdala and related brain regions. Such attenuation may be associated with a positive clinical response in depression. Bupropion XL also improved activation in the executive-function neural network. These fMRI surrogate markers offer promise for studying antidepressant and neurocognitive effects of existing and novel therapies. PMID- 17335326 TI - Efficacy of a novel biphasic controlled-release methylphenidate formula in adults with attention-deficit/hyperactivity disorder: results of a double-blind, placebo controlled crossover study. AB - OBJECTIVE: To evaluate the efficacy and safety of a new biphasic multilayer release (MLR) methylphenidate formulation in a double-blind, placebo-controlled crossover study of adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Adults 18 to 60 years of age with a DSM-IV diagnosis of ADHD entered a no medication baseline week and were then randomly assigned to once-daily MLR methylphenidate or matching placebo. Patients were titrated to optimal effect over 1 to 3 weeks followed by 2 weeks of treatment on a stable dose. The same titration protocol was repeated with the alternate treatment. Clinical Global Impressions scale (CGI) and Conners' Adult ADHD Rating Scales (Self-rated, CAARS S, and Observer-rated, CAARS-O) were collected at weekly clinic visits. The study was conducted between October 2003 and April 2004. RESULTS: Fifty patients were randomly assigned to treatment, and 39 were analyzed in a per-protocol population (23 men, 16 women; mean age = 37.9 years). CGI-Improvement scores of subjects taking MLR methylphenidate were significantly improved compared with placebo (Global Improvement: 2.6 vs. 3.7; p = .0015). MLR methylphenidate produced improvements over placebo on the ADHD Index T scores of the CAARS-S (12.2 vs. 5.4 [change from baseline score]; p = .0083) and the CAARS-O (10.9 vs. 6.6 [change from baseline score]; p = .1404). The most frequent adverse events for MLR methylphenidate and placebo were headache (26% and 24%, respectively), anorexia (22% and 6%), insomnia (22% and 8%), nervousness (20% and 4%), and nausea (16% and 8%). There were no serious adverse events. CONCLUSIONS: Once-daily MLR methylphenidate produces significant improvements in ADHD symptoms and situational behavior in adult patients with ADHD, with a prolonged duration of effect and minimal side effects, thus having the potential to improve compliance and, therefore, treatment outcomes in routine clinical use. PMID- 17335327 TI - Are day hospitals effective for acutely ill psychiatric patients? A European multicenter randomized controlled trial. AB - OBJECTIVE: Acute psychiatric day care has been proposed as an alternative to conventional inpatient care, yet the evidence of its effectiveness is inconsistent and based only on single-site studies in 3 countries. The aim of this multicenter randomized controlled trial was to establish the effectiveness of acute day hospital care in a large sample across a range of mental health care systems. METHOD: The trial was conducted from December 2000 to September 2003 in 5 European countries, with a sample of 1117 voluntarily admitted patients. Immediately before or very shortly after admission to the participating psychiatric facilities, patients were randomly allocated to treatment in a day hospital or an inpatient ward. Psychopathology, treatment satisfaction, subjective quality of life, and social disabilities were assessed at admission, at discharge, and 3 and 12 months after discharge. An intention-to-treat analysis was conducted using fixed-effects linear models with structured error covariance matrices and covariates. RESULTS: Day hospital care was as effective as conventional inpatient care with respect to psychopathologic symptoms, treatment satisfaction, and quality of life. It was more effective on social functioning at discharge and at the 3- and 12-month follow-up assessments. CONCLUSION: This study, which has more than doubled the existing evidence base, has shown that day hospital care is as effective on clinical outcomes as conventional inpatient care and more effective on social outcomes. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00153959. PMID- 17335328 TI - Nefazodone in the treatment of generalized social phobia: a randomized, placebo controlled trial. AB - OBJECTIVE: Numerous studies have demonstrated the efficacy of serotonergic antidepres-sants, particularly the selective serotonin reuptake inhibitors (SSRIs), in the treatment of social phobia. We evaluated the efficacy, safety, and tolerability of nefazodone, a 5-HT(2) antagonist, in patients with generalized social phobia (GSP). METHOD: One hundred five patients with GSP (confirmed using the Structured Clinical Interview for DSM-IV) from 4 Canadian outpatient anxiety clinics were assigned randomly to nefazodone (300-600 mg/day, flexible dose) or placebo for 14 weeks of double-blind treatment. Data were collected from October 12, 1999, through December 8, 2001. Primary efficacy outcomes were the Clinical Global Impressions-Improvement scale (CGI-I) score and the Liebowitz Social Anxiety Scale score. RESULTS: In the intent-to-treat sample, 16 (31.4%) of 51 subjects taking nefazodone and 12 (23.5%) of 51 subjects taking placebo were rated as much or very much improved on the CGI-I at endpoint (chi(2) = 0.79, p = .38). With the exception of the Social Phobia Scale, no significant differences were found in measures of social phobia when comparing the nefazodone and placebo groups. CONCLUSION: These findings suggest that nefazodone is not an effective agent in the treatment of GSP. These data parallel some recent findings with the use of the SSRI fluoxetine in GSP. The lack of efficacy of 2 serotonergic antidepressants in GSP suggests that serotonin reuptake inhibition may not be the only mechanism of action required for efficacy to occur in the treatment of GSP. PMID- 17335329 TI - Can research inform the clinical care of mental health disorders in children and adolescents? PMID- 17335330 TI - Adaptive functioning and psychiatric symptoms in adolescents with borderline personality disorder. AB - OBJECTIVE: To examine adaptive functioning and psychopathology in adolescents with DSM-IV borderline personality disorder. METHOD: 177 psychiatric outpatients (derived from 2 samples collected between March 1998 and July 1999 and between November 2000 and September 2002) aged 15 to 18 years were assessed using a structured interview for personality disorder diagnoses. Three groups, namely (1) those with a borderline personality disorder, (2) those with a personality disorder other than borderline personality disorder ("other personality disorder"), and (3) those without any personality disorder ("no personality disorder"), were compared on measures of psychiatric symptoms and psychosocial functioning. Primary outcome measures were Axis I diagnoses, Youth Self-Report, Young Adult Self-Report, Health of the Nation Outcome Scales for Children and Adolescents, Social and Occupational Functioning Assessment Scale, and sociodemographic variables. RESULTS: The borderline personality disorder group (N = 46) had the most severe psychiatric symptoms and functional impairment across a broad range of domains, followed by the other personality disorder (N = 88) and no personality disorder (N = 43) groups, respectively. Borderline personality disorder was a significant predictor over and above Axis I disorders and other personality disorder diagnoses for psychopathology, general functioning, peer relationships, self-care, and family and relationship functioning. CONCLUSIONS: The borderline personality disorder diagnosis should not be ignored or substituted by Axis I diagnoses in adolescent clinical practice, and early intervention strategies need to be developed for this disorder. PMID- 17335331 TI - Diagnostic characteristics of child bipolar I disorder: does the "Treatment of Early Age Mania (team)" sample generalize? AB - OBJECTIVE: To examine the representativeness of a randomized controlled trial (RCT) sample versus one obtained by consecutive new case ascertainment, for subjects with child bipolar I disorder. METHOD: Subjects (N = 247) were outpatients who participated in either the National Institute of Mental Health funded Phenomenology and Course of Pediatric Bipolar Disorders study or the Treatment of Early Age Mania (TEAM) study. Both studies required that subjects have current DSM-IV bipolar I disorder (manic or mixed phase) and a Children's Global Assessment Scale (CGAS) score or=3 mm were included. After initial therapy, defects were assigned randomly to a test (12 defects) or control (seven defects) procedure. Following flap reflection and root planing, test defects were filled with a bioactive ceramic filler. Mucoperiosteal flaps were replaced and sutured, and a periodontal dressing was applied. All patients received postoperative analgesics, rinsed twice daily with chlorhexidine, and were seen 2 weeks postoperatively for suture removal. Postoperative deplaquing and reinstruction in home care were performed at weekly intervals during the first month, and at 3, 6, and 12 months. At baseline and at 6 and 12 months, dental plaque, bleeding on probing (BOP), probing depth (PD), and probing attachment level (PAL) were assessed, and standardized radiographs were taken. RESULTS: The test and control groups showed similar periodontal status at baseline, with no significant differences in clinical or radiographic parameters. Plaque and BOP showed a non significant deterioration over time. PD was reduced significantly in experimental and control sites following treatment (P <0.001), but there was no significant between-group difference (P = 0.793). For PAL and radiographic bone levels, no overall within- or between-group differences were detected. CONCLUSION: The use of bioactive ceramic filler in combination with open debridement provided no significant beneficial effect over open debridement alone in the treatment of teeth with deep intraosseous defects, severe bone loss, and hypermobility. PMID- 17335364 TI - Effects of full-mouth scaling and root planing in conjunction with systemically administered azithromycin. AB - BACKGROUND: One-stage full-mouth disinfection (FMD), in which full-mouth scaling and root planing (SRP) is performed with adjunctive use of chlorhexidine, was introduced in 1995. There have been several reports on the effectiveness of this treatment protocol. However, FMD was reported to induce pyrexia frequently. We examined the effects of full-mouth SRP in conjunction with azithromycin administered orally before SRP to control the number of bacteria. The purpose of this study was to compare the effects of full-mouth SRP using azithromycin with conventional SRP. METHODS: Thirty-four subjects (17 in the test group and 17 in the control group) with severe chronic periodontitis were selected. The subjects of the test group had azithromycin 3 days before full-mouth SRP. Clinical parameters (probing depth [PD], gingival index [GI], bleeding on probing [BOP], and gingival crevicular fluid [GCF]), total number of bacteria, and number of black pigment-producing rods (BPRs) were evaluated at baseline and 5, 13, and 25 weeks after baseline. RESULTS: All clinical parameters improved in the test group more than in the control group. In the bacteriologic examination, the total number of bacteria did not change during the examination. In the test group, BPRs were not detected until 13 weeks. However, BPRs were detected in the control group by 13 weeks. CONCLUSION: It was shown that full-mouth SRP using systemically administered azithromycin was a clinically and bacteriologically useful basic periodontal treatment for severe chronic periodontitis. PMID- 17335365 TI - Subgingival chlorhexidine varnish administration as an adjunct to same-day full mouth root planing. I. Clinical observations. AB - BACKGROUND: Chemo-mechanical treatment concepts have been developed to improve the outcome of non-surgical periodontal therapy. Recently, the clinical additive value of a supersaturated chlorhexidine varnish was shown when used as an adjunct to staged scaling and root planing. The aim of this study was to investigate the clinical effects of a treatment strategy for chronic periodontitis based on a combination of same-day full-mouth root planing and subgingival chlorhexidine varnish administration. METHODS: A randomized, controlled, single-blind, parallel trial was conducted on 33 non-smoking chronic periodontitis patients. The control group received oral hygiene instructions and same-day full-mouth root planing. The test group received the same instructions and treatment; however, all pockets were disinfected using a chlorhexidine varnish. Clinical response parameters were recorded at baseline and after 1, 3, and 6 months. RESULTS: Both groups showed significant reductions in probing depth following therapy (P <0.001). There was no significant difference in full-mouth probing depth between the groups at any examination point. However, when a site-specific comparison was made, additive effects were found in the test group; an extra pocket reduction of 0.93 mm (P = 0.044) for initially deep pockets (>or=7 mm) was found at study termination. Additive clinical attachment gains seemed to be temporary. Impermanent extra pocket reductions and clinical attachment gains were found for initially medium deep pockets (4 to 6 mm). CONCLUSION: The outcome of same-day full-mouth root planing may benefit from the subgingival administration of a highly concentrated chlorhexidine varnish, at least in terms of pocket reduction in initially deep sites (>or=7 mm). PMID- 17335366 TI - Subgingival chlorhexidine varnish administration as an adjunct to same-day full mouth root planing. II. Microbiological observations. AB - BACKGROUND: Recently, the clinical additive value of a highly concentrated chlorhexidine (CHX) varnish, when applied subgingivally as an adjunct to scaling and root planing, was described. The objective of the present study was to investigate the microbiological impact of a treatment strategy for chronic periodontitis based on a combination of same-day full-mouth root planing and subgingival CHX varnish administration. METHODS: A randomized, controlled, single blind, parallel trial was conducted on 33 non-smoking chronic periodontitis patients. The control group received oral hygiene instructions and same-day full mouth root planing. The test group received the same instructions and treatment; however, all pockets also were disinfected using a supersaturated CHX varnish. Subgingival plaque samples were collected from the deepest site per quadrant in each patient at baseline and after 1, 3, and 6 months. Pooled sample analysis was performed using a multiplex polymerase chain reaction-based method for the identification of Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythensis (Tf), Treponema denticola (Td), and Prevotella intermedia (Pi). RESULTS: In terms of detection frequency and bacterial levels, significant, mainly temporary, reductions from baseline were found in both groups. When a comparison was made between the control and the test group, significant differences in the detection frequency of Tf (P = 0.024) and Td (P = 0.024), which favored the test group, were found at 1 month. A similar phenomenon was seen for Td (P = 0.031) based on bacterial levels. An important trend toward lower Tf levels in the test group also was found at 1 month (P = 0.052). Compared to baseline levels, microbiological benefits in the test group seemed to be maintained, at least in part, over a 6-month period. In contrast, all microbial levels had relapsed in the control group at study termination. CONCLUSION: The microbiological results of the present study promote the subgingival administration of a highly concentrated CHX varnish as an adjunct to same-day full-mouth root planing. PMID- 17335367 TI - Differential gene expression of periodontal ligament cells after loading of static compressive force. AB - BACKGROUND: Compressive force is an important mechanical stimulus on the periodontal ligament (PDL) and is closely related to therapeutic tooth movement. In this study, early or late response genes related to the compressive stress in PDL cells were evaluated. Particularly, the expression of interleukin (IL)-6, IL 8, and alkaline phosphatase (ALP) was studied. METHODS: The primary cultured cells from PDL were grown in a three-dimensional collagen gel, and received a continuous static compressive force (1.76 g/cm(2)). The expressed genes were screened by cDNA microarray assays for 2 or 12 hours after the initiation of the mechanical force application. The genes of interest that showed significant changes in expression in the cDNA microarray assay were analyzed further by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), enzyme linked immunoabsorbent assays (ELISA), and ALP assays. RESULTS: ALP, IL-6, and IL 8 were selected among the genes that significantly changed expression (/M/ >0.7) and subsequently were confirmed by quantitative RT-PCR. The secreted protein concentrations for IL-6, IL-8, and ALP activity were measured at 72 hours after application of continuous static compressive force. The protein level of IL-6 was significantly increased at 72 hours (P <0.001), but there was no significant change in IL-8 (P >0.05). ALP activity was decreased approximately 41.5% compared to the control (P = 0.015). CONCLUSIONS: Considering that IL-6 is a potent osteoclast activator and the compressive side of PDL during orthodontic tooth movement shows the resorption of calcified tissue, the changed expression of IL-6 and ALP in response to the static compressive force in PDL cells may contribute to the orthodontic tooth movement or alveolar bone remodeling. PMID- 17335368 TI - Cytokine profiles in crevicular fluid during orthodontic tooth movement of short and long durations. AB - BACKGROUND: Orthodontic treatment induces a distortion of the extracellular matrix of the periodontium, resulting in alterations in cytoskeletal configuration. Cytokines are known to facilitate this process by inducing cellular proliferation, differentiation, and stimulation of periodontal remodeling. The aim of the present study was to measure a panel of proinflammatory cytokines (PICs) in crevicular fluid (GCF) samples during tooth movement of short and long durations. METHODS: Twelve patients (11 to 27 years of age) participated in this study: six patients each for tooth movement of short and long duration. GCF sampling was done at different times, ranging from 24 hours to 4 months after force application. The profiles of PICs were analyzed with a multiplex technique. RESULTS: PICs were elevated significantly in the early stage of tooth movement but at different time points. Interleukin (IL) 1beta and -6 and tumor necrosis factor-alpha (TNF-alpha) reached significant levels at 24 hours; IL-8 reached a significant elevation at 1 month. During the linear stage of tooth movement, all cytokines were diminished to their baseline levels. The results demonstrated that IL-1beta, -6, and -8 and TNF-alpha play a significant role during the early stage of tooth movement but not during the linear stage. CONCLUSIONS: Once the microenvironment of periodontal tissue is activated by an orthodontic force, several key PICs are produced to trigger a cascade of cellular events. The periodontal system stabilizes at a new physiological homeostasis as indicated by the downregulation of the early-phase PICs. PMID- 17335369 TI - Anti-cardiolipin and increased serum adhesion molecule levels in patients with aggressive periodontitis. AB - BACKGROUND: We observed that a significant proportion of patients with periodontitis have elevated serum levels of beta2-glycoprotein-I-dependent anti cardiolipin (anti-CL). These prothrombotic autoantibodies, commonly found to be elevated in patients with systemic lupus erythematosus and the antiphospholipid syndrome, are associated with adverse pregnancy outcomes, such as fetal involution, prematurity, and low birth weight, and with cardiovascular sequelae, such as atherosclerosis, stroke, and myocardial infarction. Anti-CL is known to promote vascular inflammation and thrombosis. METHODS: We measured serum levels of markers of vascular inflammation, including soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1, and sE selectin, in 190 subjects with generalized aggressive or chronic periodontitis and in 90 periodontally healthy subjects. RESULTS: sVCAM-1 and sE-selectin levels were significantly higher in patients with elevated anti-CL (>15 U/ml). This relationship also was observed in the never-smoker subset of subjects, even after correction for demographic and periodontal variables. Within the diagnostic categories, sICAM-1, sVCAM-1, and sE-selectin were significantly higher in generalized aggressive periodontitis patients who had elevated anti-CL compared to those with normal anti-CL. Statistical correction for demographic and periodontal variables indicated that elevated anti-CL remained significantly associated with increased sVCAM-1 and sE-selectin in generalized aggressive periodontitis patients. CONCLUSIONS: Systemic markers of vascular inflammation in patients with aggressive periodontitis are associated with elevated levels of anti-CL. We hypothesize that a subset of periodontitis patients with elevated antiphospholipid antibodies could represent a subgroup at increased risk for obstetrical and cardiovascular sequelae. PMID- 17335370 TI - The combined genotypes of stimulatory and inhibitory Fc gamma receptors associated with systemic lupus erythematosus and periodontitis in Japanese adults. AB - BACKGROUND: The pathobiology of systemic lupus erythematosus (SLE) is similar to that of periodontitis in that the immunoglobulin G Fc receptor (FcgammaR) and proinflammatory cytokines play an important role. Genetic variations of FcgammaR and interleukin (IL)-1 are associated with susceptibility to both diseases. Therefore, we evaluated whether the combination of FcgammaR or IL-1 polymorphic genes represents a common risk factor for SLE and periodontitis. METHODS: The study population consisted of Japanese adults with SLE and periodontitis (SLE+P group; n = 46), SLE only (SLE group; n = 25), periodontitis only (P group; n = 58), and healthy individuals with no systemic or oral disease (H group; n = 44). Clinical periodontal condition was evaluated by measurement of probing depth, clinical attachment level, and alveolar bone loss. Genomic DNA was isolated from peripheral blood and analyzed for determination of FcgammaR genotypes (FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA, and FcgammaRIIIB) and IL-1 genotypes (IL 1A +4845 and IL-1B +3954) by allele-specific polymerase chain reactions or DNA sequencing. RESULTS: A significant overrepresentation of the R131 allele of stimulatory FcgammaRIIA and the 232T allele of inhibitory FcgammaRIIB was found in the SLE+P group compared to the H group (P = 0.01 and P = 0.0009, respectively). The combination of FcgammaRIIA-R131 and FcgammaRIIB-232T alleles yielded a strong association with SLE and periodontitis (SLE+P group versus P group: P = 0.01, odds ratio: 3.3; SLE+P group versus H group: P = 0.0009, odds ratio: 11.2). Furthermore, SLE patients with the combined FcgammaR risk alleles exhibited more severe periodontal tissue destruction compared to other SLE patients. The frequencies of IL-1 polymorphic alleles were too low to assess the association with SLE or periodontitis. CONCLUSION: The combination of stimulatory FcgammaRIIA and inhibitory FcgammaRIIB genotypes may increase susceptibility to SLE and periodontitis in the Japanese population. PMID- 17335371 TI - Polymorphisms within the IL-1 gene cluster: effects on cytokine profiles in peripheral blood and whole blood cell cultures of patients with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis. AB - BACKGROUND: Genetic polymorphisms of cytokines have been associated with the susceptibility, severity, and clinical outcome of inflammatory diseases, such as periodontitis and chronic arthritis. An important question to address is how interleukin (IL)-1 polymorphisms affect the cytokine profiles of patients with such diseases. METHODS: The study population consisted of Danish white adults, <35 years of age, who were diagnosed with localized aggressive periodontitis (LAgP, n = 18), generalized aggressive periodontitis (GAgP, n = 27), juvenile idiopathic arthritis (JIA, n = 10), and rheumatoid arthritis (RA, n = 23) and healthy individuals with no systemic or oral diseases (n = 25). Genotypes of IL 1A-889, IL-1A+4845, IL-1B-511, and IL-1B+3954 were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and IL-1RN variable number tandem repeat (VNTR) was detected by PCR amplification and fragment size analysis. Analysis of variance was used to evaluate the effects of IL-1 genotypes on the levels of IL-1alpha, -1beta, -1 receptor antagonist, -6, and -10; tumor necrosis factor-alpha (TNF-alpha); and lymphotoxin-alpha in peripheral blood (plasma) and in unstimulated and stimulated whole blood cell cultures from the same blood collection. RESULTS: The frequencies of IL-1 genotypes investigated did not differ significantly between diseased and control individuals. In LAgP patients, allele 2 of IL-1RN VNTR was associated with significantly higher levels of IL-1alpha, -6, and -10 and TNF-alpha, whereas allele 2 of IL-1B+3954 was associated with significantly lower levels of the same cytokines. In GAgP patients, a general lack of association was found. In JIA and RA patients, IL-1RN VNTR also influenced the cytokine levels. CONCLUSIONS: IL-1 genotypes were associated with cytokine levels in patients with aggressive periodontitis and chronic arthritis. No associations were observed in control individuals. PMID- 17335372 TI - Association of interleukin-10 gene polymorphisms with severe generalized chronic periodontitis. AB - BACKGROUND: Interleukin-10 (IL-10), an anti-inflammatory cytokine, plays a role in periodontal disease by inhibiting synthesis of proinflammatory cytokines and stimulating protective antibody production. Genetic polymorphisms in the IL-10 gene might be useful as a marker to diagnose susceptibility to periodontitis. Therefore, the aim of this study was to investigate the association between IL-10 gene polymorphisms and severe generalized chronic periodontitis (CP) in a Turkish population. METHODS: Samples of venous blood and DNA were obtained from 75 patients with severe generalized CP and 73 healthy subjects. The IL-10 promoter sequences at positions -597 and -824 were amplified by polymerase chain reaction, and polymorphisms were detected by restriction enzyme cleavage. Genotype and allele frequencies were calculated, and data were analyzed using the chi(2) test. RESULTS: There was a statistically significant difference in frequencies of genotypes (AA/CC + CA: P = 0.00007, odds ratio = 12.37, 95% confidence intervals = 2.74 to 7.77; CC/CA + AA: P = 0.001, odds ratio = 3.05, 95% confidence intervals = 1.47 to 6.33) and alleles (P = 0.0002, odds ratio = 2.61, 95% confidence intervals = 1.52 to 4.51) at position -597 C to A between patients with severe generalized CP and healthy controls, whereas there was no significant difference in genotypes and allele frequencies at position -824 C to T between patients with CP and healthy subjects. CONCLUSION: Within the limitations of sample selection and number, the IL-10 gene polymorphism at position -597 seems to be associated with severe generalized CP. PMID- 17335373 TI - Salivary enzyme levels after scaling and interleukin-1 genotypes in Japanese patients with chronic periodontitis. AB - BACKGROUND: Saliva has been used as a diagnostic fluid in medicine and dentistry. It is easy to collect using non-invasive methods. The intracellular enzymes present in saliva have been studied as markers of periodontal disease. The purpose of this study was to determine the salivary enzyme levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) after scaling and to clarify the influence of interleukin (IL)-1 genotypes on these enzyme levels. METHODS: Forty-nine Japanese patients with chronic periodontitis (24 men and 25 women; mean age: 55.1 years) were enrolled in this study. Measurements of clinical parameters including probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) and collections of stimulated whole mixed saliva were performed at baseline and 4 weeks after scaling. After evaluation of salivary AST, ALT, and LDH levels, DNA was extracted from various cells in whole saliva. IL-1A+4845 G/T genotype was determined by polymerase chain reaction amplification, followed by enzyme digestion and electrophoresis. Statistical analysis was performed by the Wilcoxon signed-rank and Mann-Whitney U tests. A significant difference was set at P <0.05. RESULTS: Mean PD, CAL, and BOP values significantly decreased after scaling (mean +/- SE: 3.2 +/- 0.1 mm to 2.6 +/- 0.1 mm in PD; 3.9 +/- 0.2 mm to 3.3 +/- 0.2 mm in CAL; and 41% +/- 4% to 18% +/- 3% in BOP) (P <0.001). The values of AST, ALT, and LDH were 77.0 +/- 7.5, 43.9 +/- 5.5, and 753.4 +/- 96.5 (units per liter [U/l]) at baseline, and significantly decreased to 55.5 +/- 6.5, 30.0 +/- 5.5, and 394.7 +/ 34.0 (U/l) after scaling, respectively (P = 0.01, P = 0.006, and P <0.001). The carriage rate of the IL-1A+4845 allele 2 was 24.5%. No difference was noted in the decrease in PD, CAL, and BOP after scaling between the carriers (N = 12) and non-carriers (N = 37) of IL-1A+4845 allele 2. However, the IL-1A allele 2 non carriers displayed a significant decrease in salivary AST and ALT levels (P <0.001), in contrast to the carriers who did not show any changes in the salivary levels of the enzymes after scaling. CONCLUSIONS: These results documented that salivary AST, ALT, and LDH levels reflect inflammation and destruction of periodontal tissue, suggesting clinically useful markers following periodontal therapy. In addition, although IL-1A+4845 alleles may not influence clinical parameters, they may influence post-scaling values of salivary AST and ALT. PMID- 17335374 TI - Verruciform xanthoma: immunohistochemical characterization of xanthoma cell phenotypes. AB - BACKGROUND: Verruciform xanthoma (VX) is a benign lesion that primarily affects the oral cavity, most frequently the gingiva. VX lesions are characterized by xanthoma cells (lipid-laden macrophages or foam cells) found in the superficial connective tissue. To characterize these foam cells further, immunohistochemical techniques were used to investigate the presence of macrophage subpopulations in oral lesions of VX. METHODS: Sixteen biopsy samples of VX lesions from the oral cavity (six from gingiva, three from palate, and seven from other mucosa) were studied. Immunohistochemical analysis was performed using antibody probes to macrophage subpopulations, including RM3/1 (reparative), 25F9 (resident), and 27E10 (inflammatory). The percentage of antibody-labeled foam cells was determined by visual counts of selected fields within lesional connective tissue. RESULTS: The proportion of VX lesions that demonstrated positive xanthoma cell reactivity with antibodies RM3/1, 25F9, and 27E10 was 100%, 88%, and 50%, respectively. Foam cells that stained positively with RM3/1, 25F9, and 27E10 represented 61.5% +/- 19.6%, 51.8% +/- 29.4%, and 10.9% +/- 14.7% of the counted cells, respectively. When results were analyzed based on anatomic location (gingiva, palate, and other mucosa), there was no difference in the percentage of positively stained cells by anatomic site for any of the three antibodies (P >0.05). Similarly, there were no differences between masticatory (gingiva and palate) and other mucosa (P >0.05). CONCLUSIONS: VX lesions contain primarily reparative and resident foam cells, with limited numbers of inflammatory macrophages, consistent with a chronic reactive process. These findings were independent of the anatomic site. PMID- 17335375 TI - Early trabecular bone healing around titanium implants: a histologic study in rabbits. AB - BACKGROUND: A detailed insight into the early healing response of trabecular bone to unloaded titanium implants is lacking. METHODS: Cylindrical implants were inserted in the tibial epiphysis of rabbits and left to heal for 1 to 42 days. Samples were processed into paraffin or methylmethacrylate sections and histomorphometrically analyzed. RESULTS: A hematoma was observed after 1 and 3 days of implant placement. In addition, small fragments of bone trabeculae were detected around the implant as a result of the implant installment procedure. Soon, osteoclasts were observed resorbing these fragments, whereas osteoblasts incorporated them in strands of new bone, thereby making them difficult to distinguish from day 7 onward. At that time, osteoblasts were detected at the edges of the preexisting bone, actively depositing new bone, resulting in maximal osteoid deposition around the implant after 28 days (58%). After 7 days of healing, the presence of basic remodeling units in the surrounding bone was already maximal (P <0.05 versus t = 1 and 3 days). This remodeling activity, together with the new bone formation, provided a firm anchoring of the implant in the trabecular bone. CONCLUSIONS: This study evaluated the early cellular events in trabecular bone surrounding titanium implants. The insertion of an implant into bone initiates a series of biologic processes, including the formation of a hematoma, shattered bone fragments adjacent to the implantation site, intensive bone remodeling, and the formation of new bone, eventually leading to the osseointegration of the implant. PMID- 17335376 TI - Saliva from subjects harboring Actinobacillus actinomycetemcomitans kills Streptococcus mutans in vitro. AB - BACKGROUND: Previous research indicated that patients with localized aggressive periodontitis (LAgP) had minimal proximal decay. We speculated that differences in these two proximal dental diseases (LAgP and proximal decay) in LAgP could be due to the effect of saliva on the growth of key microorganisms related to these two infections. Carbon dioxide (CO(2)) is required for growth of Actinobacillus actinomycetemcomitans (Aa), the reputed cause of LAgP. Bicarbonate, a source of CO(2), buffers acid production by Streptococcus mutans (Sm), a key organism associated with caries. The purpose of this study was to determine whether the saliva of LAgP patients and subjects with Aa had higher levels of bicarbonate, or an elevated pH, and/or reduced survival of Sm. METHODS: Eleven Aa-positive subjects (seven with LAgP) were matched with 11 Aa-negative controls. A total of 5 ml saliva obtained from each subject was tested for CO(2) levels, pH, and effects on survival of Aa and Sm. Saliva from 22 additional subjects was used for confirmatory data. RESULTS: CO(2) levels in the test group (Aa-positive subjects) and controls (Aa-negatives) were similar. No clinically relevant differences were found in salivary pH. However, saliva from the test group killed Sm by more than two logs (P <0.05). No effect was seen on Aa. The saliva from the Aa-negative group killed Aa by two logs (P <0.05). No effect was seen on Sm. CONCLUSION: Aa positive subjects had a salivary factor that significantly reduced survival of Sm, which may help to explain the fact that this group typically has minimal proximal decay. PMID- 17335377 TI - A histologic and histometric assessment of the influence of nicotine on alveolar bone loss in rats. AB - BACKGROUND: Cigarette smoking has long been recognized as a risk factor for periodontal disease. The aim of this study was to perform quantitative and qualitative analyses of bone loss in the furcation region of periodontally healthy rats after daily systemic administration of nicotine or saline solution. METHODS: Thirty adult male Wistar rats were assigned randomly to twice daily subcutaneous injections of saline solution (control, group C) or nicotine (group N). The animals were sacrificed at 37, 44, or 51 days after the first subcutaneous injection. The specimens were processed for serial histologic sections, and the area of bone loss in the furcation region of the second molar was analyzed histometrically. RESULTS: Greater bone loss was detected in group N compared to group C on day 37 (16.36 +/- 5.84 mm(2) and 7.24 +/- 2.66 mm(2)), day 44 (15.12 +/- 4.57 mm(2) and 7.76 +/- 1.35 mm(2)), and day 51 (18.80 +/- 3.71 mm(2) and 8.74 +/- 2.61 mm(2)), respectively (P <0.05). Extension of bone loss appeared greater in the furcation region of group N where a thinner trabeculae bone was found. After day 37, bone loss did not increase significantly. CONCLUSIONS: Daily systemic administration of nicotine resulted in significantly greater bone loss in the furcation region compared to saline solution. This indicated a close association between nicotine and periodontal morbidity in rats. PMID- 17335378 TI - Nicotine and lipopolysaccharide affect cytokine expression from gingival fibroblasts. AB - BACKGROUND: This in vitro study investigated the influence of nicotine, lipopolysaccharide (LPS), and a combination of both agents on cytokine expression from human gingival fibroblasts (HGFs). METHODS: HGFs were exposed for 48 hours to 250 microg/ml nicotine, 1 microg/ml Porphyromonas gingivalis LPS, or both. The expression of multiple cytokines was detected in the HGFs conditioned media using cytokine protein arrays. RESULTS: The untreated HGFs expressed several cytokines, which included relatively high levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1). They also expressed low levels of growth regulated oncogene (GRO), IL-3, and IL-10. Nicotine had the greatest effect on the expression of GRO-alpha, IL-7, IL-10, and IL-15 compared to the untreated control. P. gingivalis LPS had the greatest effect on the expression of GRO alpha; IL-7; IL-10; and RANTES (regulated on activation, normal T-cell expressed, and presumably secreted) compared to the untreated control. The combination of both agents had the biggest impact on the expression of GRO-alpha, IL-7, IL-10, IL-15, RANTES, and interferon-gamma (IFN-gamma) compared to the untreated control. CONCLUSION: HGFs exposed to nicotine, P. gingivalis LPS, or a combination of both agents increased the expression of multiple cytokines. PMID- 17335379 TI - Effect of a cyclooxygenase-2 inhibitor on interleukin-1beta-stimulated activation of the transcription factor nuclear factor-kappa B in human gingival fibroblasts. AB - BACKGROUND: In previous work, the cyclooxygenase-2 inhibitor NS-398 inhibited interleukin (IL)-1beta-stimulated prostaglandin E(2) (PGE(2)) production almost completely while partially inhibiting IL-6 production in aggressive periodontitis (AgP) human gingival fibroblasts. PGE(2) and the transcription factor nuclear factor-kappa B (NF-kappaB) regulate IL-1beta-stimulated IL-6 production. Cytoplasmic NF-kappaB is bound to inhibitors (IkappaB proteins). IL-1beta initiates a cascade resulting in phosphorylation and degradation of IkappaB, allowing nuclear translocation of NF-kappaB and target gene activation. The purpose of this study was to determine whether NS-398 inhibited phosphorylation of IkappaB and NF-kappaB activation. METHODS: AgP fibroblasts (1 to 2 x 10(6)) were exposed to IL-1beta (1 x 10(11)M) with or without NS-398 (10 nM) in serum free medium. The NF-kappaB subunit p65 and phospho-IkappaBalpha were measured in whole cell, cytoplasmic, or nuclear extracts, using colorimetric assays. Enzyme linked immunosorbent assays were used to measure PGE(2) and IL-6 production by 2.5 x 10(4) cells after exposure to IL-1beta with or without NS-398 in serum-free medium. RESULTS: Consistent with previous results, NS-398 reduced IL-1beta stimulated PGE(2) by approximately 98% (P <0.001) and IL-6 by approximately 65% (P <0.001). IL-1beta increased nuclear and cytoplasmic p65 ( approximately 8-fold [P <0.001] and approximately 2.5-fold [P <0.03], respectively) over control levels. NS-398 reduced IL-1beta-stimulated nuclear and cytoplasmic p65 to control levels. IL-1beta increased phospho-IkappaBalpha in whole cell extracts by a maximum of approximately 9.5 times (P = 0.0001), and this was inhibited significantly by NS-398 (P 10 years by an oral mode of delivery for the treatment of osteopenia, osteoporosis, and Paget's disease of bone. The purpose of this report is to review the literature associated with bisphosphonate use that could impact bone healing and to report a case of bone necrosis in a patient on long-term oral bisphosphonates. METHODS: A Medline search was carried out to find relevant articles from both medical and dental literature between 1960 and 2006. A patient, who had been taking an oral bisphosphonate for >10 years, developed unexplained clinical signs of bone necrosis after routine dental implant placement. This case was followed, documented, and the treatment of the osteonecrosis described. RESULTS: A summary of how bisphosphonates may play a role in wound healing is presented. The compromised healing noted in a patient, who was under long-term oral bisphosphonate use, was successfully treated with systemic antibiotics, local microbial mouthrinse, and aggressive defect management (detoxification and mixture of bone graft and tetracycline). CONCLUSIONS: This case suggests that patients under long-term oral bisphosphonate use should be treated with caution. Well-controlled, prospective clinical trials on the effect of oral bisphosphonates on bone are warranted to determine which patients may be at risk for such complications. PMID- 17335386 TI - Selective visual dimension weighting deficit after left lateral frontopolar lesions. AB - The left lateral frontopolar (LFP) cortex showed dimension change-related activation in previous event-related functional magnetic resonance imaging studies of visual singleton feature search with non-brain-lesioned participants. Here, we tested the hypothesis that LFP actively supports changes of attention from the old to the new target-defining dimension in singleton feature search. Singleton detection was selectively slowed in this task when the target-defining dimension changed in patients with left LFP lesions, compared with patients with frontomedian lesions as well as with matched controls without brain lesions. We discuss a potential role of LFP in change detection when the optimal allocation of dimension-based attention is not clearly defined by the task. PMID- 17335387 TI - Auditory brainstem correlates of perceptual timing deficits. AB - Children with language-based learning problems often exhibit pronounced speech perception difficulties. Specifically, these children have increased difficulty separating brief sounds occurring in rapid succession (temporal resolution). The purpose of this study was to better understand the consequences of auditory temporal resolution deficits from the perspective of the neural encoding of speech. The findings provide evidence that sensory processes relevant to cognition take place at much earlier levels than traditionally believed. Thresholds from a psychophysical backward masking task were used to divide children into groups with good and poor temporal resolution. Speech-evoked brainstem responses were analyzed across groups to measure the neural integrity of stimulus-time mechanisms. Results suggest that children with poor temporal resolution do not have an overall neural processing deficit, but rather a deficit specific to the encoding of certain acoustic cues in speech. Speech understanding relies on the ability to attach meaning to rapidly fluctuating changes of both the temporal and spectral information found in consonants and vowels. For this to happen properly, the auditory system must first accurately encode these time varying acoustic cues. Speech perception difficulties that often co-occur in children with poor temporal resolution may originate as a neural encoding deficit in structures as early as the auditory brainstem. Thus, speech-evoked brainstem responses are a biological marker for auditory temporal processing ability. PMID- 17335388 TI - Setting the stage for automatic syntax processing: the mismatch negativity as an indicator of syntactic priming. AB - The present study investigated the automaticity of morphosyntactic processes and processes of syntactic structure building using event-related brain potentials. Two experiments were conducted, which contrasted the impact of local subject-verb agreement violations (Experiment 1) and word category violations (Experiment 2) on the mismatch negativity, an early event-related brain potential component reflecting automatic auditory change detection. The two violation types were realized in two-word utterances comparable with regard to acoustic parameters and structural complexity. The grammaticality of the utterances modulated the mismatch negativity response in both experiments, suggesting that both types of syntactic violations were detected automatically within 200 msec after the violation point. However, the topographical distribution of the grammaticality effect varied as a function of violation type, which indicates that the brain mechanisms underlying the processing of subject-verb agreement and word category information may be functionally distinct even at this earliest stage of syntactic analysis. The findings are discussed against the background of studies investigating syntax processing beyond the level of two-word utterances. PMID- 17335389 TI - Impaired executive control is associated with a variation in the promoter region of the tryptophan hydroxylase 2 gene. AB - Current models of attention describe attention not as a homogenous entity but as a set of neural networks whose measurement yields a set of three endophenotypes alerting, orienting, and executive control. Previous findings revealed different neuroanatomical regions for these subsystems, and data from twin studies indicate differences in their heritability. The present study investigated the molecular genetic basis of attention in a sample of 100 healthy subjects. Attention performance was assessed with the attention network test that distinguishes alerting, orienting, and executive control (conflict) using a simple reaction time paradigm with different cues and congruent and incongruent flankers. Two gene loci on candidate genes for cognitive functioning, the functional catechol-O methyltransferase (COMT) VAL158MET and the tryptophan hydroxylase 2 (TPH2) -703 G/T promoter polymorphism, were tested for possible associations with attention. COMT is involved in the catabolism of dopamine, and TPH is the rate-limiting enzyme for serotonin synthesis. Results showed no effect of the COMT polymorphism on attention performance. However, the TT genotype of TPH2 -03 G/T was significantly associated with more errors (a possible indicator of impaired impulse control; p = .001) and with decreased performance in executive control (p = .001). This single-nucleotide polymorphism on the TPH2 gene explained more than 10% of the variance in both indicators of attention stressing the role of the serotonergic system for cognitive functions. PMID- 17335390 TI - How to compare two quantities? A computational model of flutter discrimination. AB - A task that has been intensively studied at the neural level is f lutter discrimination. I argue that f lutter discrimination entails a combination of a temporal assignment problem and a quantity comparison problem, and propose a neural network model of how these problems are solved. The network combines unsupervised and one-layer supervised training. The unsupervised part clusters input features (stimulus + time window) and the supervised part categorizes the resulting clusters. After training, the model shows a good fit with both neural and behavioral properties. New predictions are outlined and links with other cognitive domains are pointed out. PMID- 17335391 TI - Spatio-temporal brain dynamics underlying saccade execution, suppression, and error-related feedback. AB - Human and nonhuman animal research has outlined the neural regions that support saccadic eye movements. The aim of the current work was to outline the sequence by which distinct neural regions come on-line to support goal-directed saccade execution and error-related feedback. To achieve this, we obtained behavioral responses via eye movement recordings and neural responses via magnetoencephalography (MEG), concurrently, while participants performed an antisaccade task. Neural responses were examined with respect to the onset of the saccadic eye movements. Frontal eye field and visual cortex activity distinguished subsequently successful goal-directed saccades from (correct and erroneous) reflexive saccades prior to the deployment of the eye movement. Activity in the same neural regions following the saccadic movement distinguished correct from incorrect saccadic responses. Error-related activity in the frontal eye fields preceded that from visual regions, suggesting a potential feedback network that may drive corrective eye movements. This work provides the first empirical demonstration of simultaneous remote eyetracking and MEG recording. The coupling of behavioral and neuroimaging technologies, used here to characterize dynamic brain networks underlying saccade execution and error-related feedback, demonstrates a novel within-paradigm converging evidence approach by which to outline the neural underpinnings of cognition. PMID- 17335392 TI - Brain activation for lexical decision and reading aloud: two sides of the same coin? AB - This functional magnetic resonance imaging study compared the neuronal implementation of word and pseudoword processing during two commonly used word recognition tasks: lexical decision and reading aloud. In the lexical decision task, participants made a finger-press response to indicate whether a visually presented letter string is a word or a pseudoword (e.g., "paple"). In the reading aloud task, participants read aloud visually presented words and pseudowords. The same sets of words and pseudowords were used for both tasks. This enabled us to look for the effects of task (lexical decision vs. reading aloud), lexicality (words vs. nonwords), and the interaction of lexicality with task. We found very similar patterns of activation for lexical decision and reading aloud in areas associated with word recognition and lexical retrieval (e.g., left fusiform gyrus, posterior temporal cortex, pars opercularis, and bilateral insulae), but task differences were observed bilaterally in sensorimotor areas. Lexical decision increased activation in areas associated with decision making and finger tapping (bilateral postcentral gyri, supplementary motor area, and right cerebellum), whereas reading aloud increased activation in areas associated with articulation and hearing the sound of the spoken response (bilateral precentral gyri, superior temporal gyri, and posterior cerebellum). The effect of lexicality (pseudoword vs. words) was also remarkably consistent across tasks. Nevertheless, increased activation for pseudowords relative to words was greater in the left precentral cortex for reading than lexical decision, and greater in the right inferior frontal cortex for lexical decision than reading. We attribute these effects to differences in the demands on speech production and decision-making processes, respectively. PMID- 17335393 TI - Seeing fearful body language overcomes attentional deficits in patients with neglect. AB - Survival depends to some extent on the ability to detect salient signals and prepare an appropriate response even when attention is engaged elsewhere. Fearful body language is a salient signal of imminent danger, easily observable from a distance and indicating to the observer which adaptive action to prepare for. Here we investigated for the first time whether fearful body language modulates the spatial distribution of attention and enhances visual awareness in neurological patients with severe attentional disorders. Patients with visual extinction and hemispatial neglect following right parietal injury have a rightward attentional bias accompanied by loss of awareness for contralesional left stimuli, especially when competing stimuli appear to the right. Three such patients were tested with pictures of fearful, happy, and neutral bodily expressions briefly presented either unilaterally in the left or right visual field, or to both fields simultaneously. On bilateral trials, unattended and task irrelevant fearful bodily expressions modulated attentional selection and visual awareness. Fearful bodily expressions presented in the contralesional unattended visual field simultaneously with neutral bodies in the ipsilesional field were detected more often than left-side neutral or happy bodies. This demonstrates that despite pathological inattention and parietal damage, emotion and action related information in fearful body language may be extracted automatically, biasing attentional selection and visual awareness. Our findings open new perspectives on the role of bodily expressions in attentional selection and suggest that a neural network in intact fronto-limbic and visual areas may still mediate reorienting of attention and preparation for action upon perceiving fear in others. PMID- 17335394 TI - An event-related fMRI Study of exogenous facilitation and inhibition of return in the auditory modality. AB - The orienting of attention to different locations in space is fundamental to most organisms and occurs in all sensory modalities. Orienting has been extensively studied in vision, but to date, few studies have investigated neuronal networks underlying automatic orienting of attention and inhibition of return to auditory signals. In the current experiment, functional magnetic resonance imaging and behavioral data were collected while healthy volunteers performed an auditory orienting task in which a monaurally presented tone pip (cue) correctly or incorrectly cued the location of a target tone pip. The stimulus onset asynchrony (SOA) between the cue and target was 100 or 800 msec. Behavioral results were consistent with previous studies showing that valid auditory cues produced facilitation at the short SOA and inhibition of return at the long SOA. Functional results indicated that the reorienting of attention (100 msec SOA) and inhibition of return (800 msec SOA) were mediated by both common and distinct neuronal structures. Both attention mechanisms commonly activated a network consisting of fronto-oculomotor areas, the left postcentral gyrus, right premotor area, and bilateral tonsil of the cerebellum. Several distinct areas of frontal and parietal activation were identified for the reorienting condition, whereas the right inferior parietal lobule was the only structure uniquely associated with inhibition of return. PMID- 17335395 TI - Beta-adrenergic modulation of cognitive flexibility during stress. AB - Stress-induced activation of the locus ceruleus-norepinephrine (LC-NE) system produces significant cognitive and behavioral effects, including enhanced arousal and attention. Improvements in discrimination task performance and memory have been attributed to this stress response. In contrast, for other cognitive functions that require cognitive flexibility, increased activity of the LC-NE system may produce deleterious effects. The aim of the present study was to determine the effect of pharmacological modulation of the LC-NE system on stress induced impairments in cognitive flexibility performance in healthy individuals. Cognitive performance, plus psychological and physiological parameters for 16 adults without any history of anxiety disorders, was assessed during four test sessions: stress and no-stress, with each condition tested after administration of propranolol and placebo. The Trier Social Stress Test, a public-speaking and mental arithmetic stressor, was presented to participants for the stress sessions, whereas a similar, but nonstressful, control task (reading, counting) was utilized for the no-stress sessions. Tests of cognitive flexibility included lexical-semantic and associative problem-solving tasks (anagrams, Compound Remote Associates Test). Visuo-spatial memory and motor processing speed tests served as control tasks. Results indicate that (1) stress impaired performance on cognitive flexibility tasks, but not control tasks; (2) compared to placebo, cognitive flexibility improved during stress with propranolol. Therefore, psychological stress, such as public speaking, negatively impacts performance on tasks requiring cognitive flexibility in normal individuals, and this effect is reversed by beta-adrenergic antagonism. This may provide support for the hypothesis that stress-related impairments in cognitive flexibility are related to the noradrenergic system. PMID- 17335396 TI - Local field potentials and spikes in the human medial temporal lobe are selective to image category. AB - Local field potentials (LFPs) reflect the averaged dendrosomatic activity of synaptic signals of large neuronal populations. In this study, we investigate the selectivity of LFPs and single neuron activity to semantic categories of visual stimuli in the medial temporal lobe of nine neurosurgical patients implanted with intracranial depth electrodes for clinical reasons. Strong selectivity to the category of presented images was found for the amplitude of LFPs in 8% of implanted microelectrodes and for the firing rates of single and multiunits in 14% of microelectrodes. There was little overlap between the LFP- and spike selective microelectrodes. Separate analysis of the power and phase of LFPs revealed that the mean phase was category-selective around the theta frequency range and that the power of the LFPs was category-selective for high frequencies around the gamma rhythm. Of the 36 microelectrodes with amplitude-selective LFPs, 30 were found in the hippocampus. Finally, it was possible to readout information about the category of stimuli presented to the patients with both spikes and LFPs. Combining spiking and LFP activity enhanced the decoding accuracy in comparison with the accuracy obtained with each signal alone, especially for short time intervals. PMID- 17335397 TI - Topography and dynamics of associative long-term memory retrieval in humans. AB - The present study investigated the neurophysiological processes underlying associative long-term memory retrieval of objects and spatial positions by means of a modified fan paradigm with cued recall and two neuroimaging methods (electroencephalogram [EEG] and functional magnetic resonance imaging). In an acquisition phase, either one stimulus or two stimuli became associated with a noun. During retrieval, probe stimuli comprising noun pairs were presented, and participants had to recall the respective associations and decided whether the nouns are linked to each other via a commonly associated stimulus. With this design, the quality and quantity of recalled associations was systematically varied, whereas the triggering stimuli and response requirements were held constant in all experimental conditions. Recall time proved to be directly related to the number of associations fanning out from a retrieval cue. Correspondingly, the hemodynamic response (blood oxygen level-dependent [BOLD] signal) and the amplitude of slow negative EEG potentials increased monotonically with the number of associations in both left anterior and bilateral posterior cortical areas. These effects were consistently observed with content-specific topographies for the two distinct materials. Furthermore, the multimethod approach revealed a close temporal link between response times and event-related slow potential changes on the one side and a close topographical and amplitude correspondence between slow potentials and BOLD signal changes on the other. The integrated results suggest that the neuronal dynamics of associative memory retrieval are equivalent for different types of associations, but that the structural basis is clearly content-specific. PMID- 17335398 TI - Effects of rTMS conditioning over the fronto-parietal network on motor versus visual attention. AB - Many studies have shown that visuospatial orienting attention depends on a network of frontal and parietal areas in the right hemisphere. Rushworth et al. [Rushworth, M. F., Krams, M., & Passingham, R. E. The attentional role of the left parietal cortex: The distinct lateralization and localization of motor attention in the human brain. Journal of Cognitive Neuroscience, 13, 698-710, 2001] have recently provided evidence for a left-lateralized network of parietal areas involved in motor attention. Using two variants of a cued reaction time (RT) task, we set out to investigate whether high-frequency repetitive transcranial magnetic stimulation (rTMS; 5 Hz) delivered "off-line" in a virtual lesion paradigm over the right or left dorsolateral prefrontal cortex (DLPFC) or the posterior parietal cortex (PPC) would affect performance in a motor versus a visual attention task. Although rTMS over the DLPFC on either side did not affect RT performance on a spatial orienting task, it did lead to an increase in the RTs of invalidly cued trials in a motor attention task when delivered to the left DLPFC. The opposite effect was found when rTMS was delivered to the PPC: In this case, conditioning the right PPC led to increased RTs in invalidly cued trials located in the left hemispace, in the spatial orienting task. rTMS over the PPC on either side did not affect performance in the motor attention task. This double dissociation was evident in the first 10 min after rTMS conditioning. These results enhance our understanding of the networks associated with attention. They provide evidence of a role for the left DLPFC in the mechanisms of motor preparation, and confirm Mesulam's original proposal for a right PPC dominance in spatial attention [Mesulam, M. M. A cortical network for directed attention and unilateral neglect. Annals of Neurology, 10, 309-325, 1981]. PMID- 17335399 TI - Experience-dependent plasticity of conceptual representations in human sensory motor areas. AB - Concepts are composed of features related to different sensory and motor modalities such as vision, sound, and action. It is a matter of controversy whether conceptual features are represented in sensory-motor areas reflecting the specific learning experience during acquisition. In order to address this issue, we assessed the plasticity of conceptual representations by training human participants with novel objects under different training conditions. These objects were assigned to categories such that for one class of categories, the overall shape was diagnostic for category membership, whereas for the other class, a detail feature affording a particular action was diagnostic. During training, participants were asked to either make an action pantomime toward the detail feature of the novel object or point to it. In a categorization task at test, we assessed the neural correlates of the acquired conceptual representations by measuring electrical brain activity. Here, we show that the same object is differentially processed depending on the sensory-motor interactions during knowledge acquisition. Only in the pantomime group did we find early activation in frontal motor regions and later activation in occipito parietal visual-motor regions. In the pointing training group, these effects were absent. These results show that action information contributes to conceptual processing depending on the specific learning experience. In line with modality specific theories of conceptual memory, our study suggests that conceptual representations are established by the learning-based formation of cell assemblies in sensory-motor areas. PMID- 17335400 TI - Long-term expertise with artificial objects increases visual competition with early face categorization processes. AB - The degree of commonality between the perceptual mechanisms involved in processing faces and objects of expertise is intensely debated. To clarify this issue, we recorded occipito-temporal event-related potentials in response to faces when concurrently processing visual objects of expertise. In car experts fixating pictures of cars, we observed a large decrease of an evoked potential elicited by face stimuli between 130 and 200 msec, the N170. This sensory suppression was much lower when the car and face stimuli were separated by a 200 msec blank interval. With and without this delay, there was a strong correlation between the face-evoked N170 amplitude decrease and the subject's level of car expertise as measured in an independent behavioral task. Together, these results show that neural representations of faces and nonface objects in a domain of expertise compete for visual processes in the occipito-temporal cortex as early as 130-200 msec following stimulus onset. PMID- 17335401 TI - Spontaneous large volume adipose tissue generation from a vascularized pedicled fat flap inside a chamber space. AB - A novel method of spontaneous generation of new adipose tissue from an existing fat flap is described. A defined volume of fat flap based on the superficial inferior epigastric vascular pedicle in the rat was elevated and inset into a hollow plastic chamber implanted subcutaneously in the groin of the rat. The chamber walls were either perforated or solid and the chambers either contained poly(D,L-lactic-co-glycolic acid) (PLGA) sponge matrix or not. The contents were analyzed after being in situ for 6 weeks. The total volume of the flap tissue in all groups except the control groups, where the flap was not inserted into the chambers, increased significantly, especially in the perforated chambers (0.08 +/ 0.007 mL baseline compared to 1.2 +/- 0.08 mL in the intact ones). Volume analysis of individual component tissues within the flaps revealed that the adipocyte volume increased and was at a maximum in the chambers without PLGA, where it expanded from 0.04 +/- 0.003 mL at insertion to 0.5 +/- 0.08 mL (1250% increase) in the perforated chambers and to 0.16 +/- 0.03 mL (400% increase) in the intact chambers. Addition of PLGA scaffolds resulted in less fat growth. Histomorphometric analysis rather than simple hypertrophy documented an increased number of adipocytes. The new tissue was highly vascularized and no fat necrosis or atypical changes were observed. PMID- 17335402 TI - Encapsulation, in vitro characterization, and in vivo biocompatibility of Sertoli cells in alginate-based microcapsules. AB - A method for microencapsulation of isolated neonatal porcine Sertoli cells is described. Using a conventional alginate-poli-L-ornithine encapsulation procedure, which has been used in our laboratory for almost two decades to envelop pancreatic islets, we observed significant loss of Sertoli cell viability, possibly due to excessive Ca(2+) ion exposure. Replacing calcium with barium, or shortening the incubation period in the presence of Ca ions, we obtained barium or calcium alginate gel microbeads that did not alter morphology and viability of the encapsulated Sertoli cells. The procedure might permit access to a novel approach to immunologically alter cell graft acceptance. PMID- 17335403 TI - Information processing in the primate retina: circuitry and coding. AB - The function of any neural circuit is governed by connectivity of neurons in the circuit and the computations performed by the neurons. Recent research on retinal function has substantially advanced understanding in both areas. First, visual information is transmitted to the brain by at least 17 distinct retinal ganglion cell types defined by characteristic morphology, light response properties, and central projections. These findings provide a much more accurate view of the parallel visual pathways emanating from the retina than do previous models, and they highlight the importance of identifying distinct cell types and their connectivity in other neural circuits. Second, encoding of visual information involves significant temporal structure and interactions in the spike trains of retinal neurons. The functional importance of this structure is revealed by computational analysis of encoding and decoding, an approach that may be applicable to understanding the function of other neural circuits. PMID- 17335404 TI - Anthrax toxin: receptor binding, internalization, pore formation, and translocation. AB - Anthrax toxin consists of three nontoxic proteins that self-assemble at the surface of receptor-bearing mammalian cells or in solution, yielding a series of toxic complexes. Two of the proteins, called Lethal Factor (LF) and Edema Factor (EF), are enzymes that act on cytosolic substrates. The third, termed Protective Antigen (PA), is a multifunctional protein that binds to receptors, orchestrates the assembly and internalization of the complexes, and delivers them to the endosome. There, the PA moiety forms a pore in the endosomal membrane and promotes translocation of LF and EF to the cytosol. Recent advances in understanding the entry process include insights into how PA recognizes its two known receptors and its ligands, LF and EF; how the PA:receptor interaction influences the pH-dependence of pore formation; and how the pore functions in promoting translocation of LF and EF across the endosomal membrane. PMID- 17335405 TI - A comparative study of root coverage using acellular dermal matrix with and without enamel matrix derivative. AB - BACKGROUND: The aim of this study was to compare root coverage using acellular dermal matrix (ADM) with and without enamel matrix derivative (EMD) on the percentage of root coverage, probing attachment level, and the amount of keratinized tissue in the treatment of localized recession. METHODS: Eighty-two contralateral sites in 14 patients with >or=2 mm of Miller Class I or III buccal tissue recession were treated. Forty-one test sites were treated with coronally advanced flap (CAF) using ADM in conjunction with EMD, whereas 41 control sites were treated with CAF using ADM alone. A split-mouth design was used for this study with 82 sites. Patients were followed for 3 and 6 months. A paired t test was conducted with the subject as the unit of analysis. RESULTS: Based on paired t tests, both groups had significant improvement in the percentage of root coverage, probing attachment levels, and increased keratinized tissue. Only keratinized tissue in the test group demonstrated a statistically significant greater increase compared to controls at the 6-month evaluation (P = 0.006). CONCLUSION: The use of EMD in conjunction with ADM resulted in a statistically significant effect on keratinized tissue increase, but no significant effects on probing attachment level or percentage of root surface coverage. PMID- 17335406 TI - Dry powder inhalation versus wet nebulisation delivery of antibiotics in cystic fibrosis patients. AB - Inhalation of antipseudomonal antibiotics is a cornerstone in treating cystic fibrosis patients. It has shown to be effective in slowing down the process of pulmonary deterioration and decreasing the incidence of infectious exacerbations. The focus is now on innovating drug delivery devices, sometimes combined with specific drug formulations, which allow for the administration of large doses in a short time frame and in a reproducible way. Adaptive aerosol delivery devices are promising, but do not have a distinct position as yet because of the lack of long-term data. The position of dry powder inhalation of antibiotics in cystic fibrosis treatment is still confined to pilot studies. Until more clinical data are available, the suboptimal, conventional jet nebulisers are the mainstay in antipseudomonal inhalation therapy in cystic fibrosis. PMID- 17335407 TI - Liposome-based drug delivery to alveolar macrophages. AB - The recent development of liposomal formulations compatible with aerosol delivery has expanded the potential to utilise chemotherapeutic agents directly targeted to the lungs more effectively. These are agents that would otherwise not be used because of their low solubility or toxicity. Various properties of liposomal carriers, including size, surface charge, composition and the presence of ligands, alter their efficacy and specificity towards alveolar macrophages to a great extent. This editorial summarises the advances in liposome-based drug delivery to alveolar macrophages. PMID- 17335408 TI - Mesoporous silicon: a platform for the delivery of therapeutics. AB - Nanostructuring materials can radically change their properties. Two interesting examples highlighted here are nanoscale porosity inducing biodegradability, and nanoscale confinement affecting the physical form of an entrapped drug. Mesoporous silicon is under increasing study for drug-delivery applications, and is the topic of this review. The authors focus on those properties of most relevance to this application, as well as those recent studies published on small molecule and peptide/protein delivery. PMID- 17335409 TI - Transdermal rotigotine: a new non-ergot dopamine agonist for the treatment of Parkinson's disease. AB - An important conceptual development to avoid the occurrence of motor dyskinesias in Parkinson's disease is continuous dopaminergic stimulation. Studies in animal models and humans suggest that continuous dopaminergic stimulation could be achieved by the infusions of different dopamine agonists or levodopa, and may significantly reduce the risk of dyskinesias associated with treatment strategies utilising pulsatile treatment options. However, so far, these techniques have either necessitated frequent intake of oral therapy or invasive parenteral treatment. The rotigotine transdermal delivery system represents a significant development that allows a constant delivery of a non-ergot dopamine agonist using a once-daily regimen, achieving steady plasma levels. Clinical trials demonstrate the efficacy of rotigotine in early and advanced Parkinson's disease, with important implications for treatment of non-motor symptoms of Parkinson's disease. PMID- 17335410 TI - The microfabricated electrokinetic pump: a potential promising drug delivery technique. AB - Directly delivering liquid using direct current power was a dream for 40 years. Now, the electrokinetic pump can accomplish it. This review reports recent developments in microfabricated electrokinetic pump technologies and their applications, and also discusses the electrophoresis pump and elctroosmotic pump, as well as the materials and fabrication methods frequently used for the production of these pump devices. Electrokinetics pumps can be used to deliver pure water, pure polar organic solvents, inorganic buffer and biomacromolecules, with wide applications for the delivery of liquids. These devices have the potential to become drug delivery systems, for the precise, timed and/or targeted delivery of drugs. Future trends, limitations and possibilities are also discussed. PMID- 17335411 TI - Photodynamic therapy and cancer: a brief sightseeing tour. AB - Photodynamic therapy (PDT) combines a drug (a photosensitiser or photosensitising agent) with a specific type of light to kill cancer cells. It is a minimally invasive treatment, with great potential in malignant disease and premalignant conditions. Following the administration of the photosensitiser, light of the appropriate wavelength is directed onto the abnormal tissue where the drug has preferentially accumulated. Upon light activation, the photosensitiser transfers its excess energy to molecular oxygen to produce an excited state (i.e., the highly reactive singlet oxygen) that causes oxidative damage at the site of its generation. The energy transfer occurs either directly to oxygen or through an indirect mechanism that requires the formation of intermediate radical species. Many photosensitisers have been developed, but only a few have been approved for therapy in humans. Basic research in model systems (animals, cell lines) has unravelled some fundamental cellular processes involved in the cell response to PDT. The exploitation of relevant molecular observations, the discovery and introduction of new sensitisers, the progress in the light delivery systems and light dosimetry are all concurring to the increase of PDT therapeutic efficacy. However, this field has not yet reached maturity. This review briefly analyses the relevant properties of most photosensitisers and their field of application. Special attention is dedicated to the effects observed in model cancer systems; speculation and suggestions of possible future research directions are also offered. PMID- 17335412 TI - Gadolinium(III)-based blood-pool contrast agents for magnetic resonance imaging: status and clinical potential. AB - Blood-pool MRI contrast agents have enormous potential to aid sensitive magnetic resonance detection and yield definitive diagnostic data of cancer and diseases of the cardiovascular system. Many attempts have been initiated to design macromolecular gadolinium (Gd[III]) complexes as magnetic resonance imaging blood pool contrast agents, as macromolecules do not readily diffuse across healthy vascular endothelium, and remain intravascular. Although extremely efficacious in detecting and characterizing pathologic tissue, clinical development of these agents has been limited by potential toxicity concerns from incomplete Gd(III) clearance. Recent innovative technologies, such as reversible protein-binding contrast agents and biodegradable macromolecular contrast agents, may be valuable alternatives that combine the effective imaging characteristics of an intravascular contrast agent and the safety of clinically approved low-molecular weight Gd(III) chelates. PMID- 17335413 TI - Dose accuracy and injection force dynamics of a novel disposable insulin pen. AB - SoloStar (sanofi-aventis) is a new, disposable insulin pen for the administration of insulin glargine (Lantus, sanofi-aventis) or insulin glulisine (Apidra, sanofi aventis). SoloStar was developed to address a wide range of patient needs and demonstrates advancement over previous devices, owing to its appropriate combination of ergonomically-tested and mechanically improved features. The authors report the results of key investigations carried out by sanofi-aventis as part of the SoloStar development plan, including dose accuracy and injection force testing. Comparisons between SoloStar and two commonly used pens, FlexPen (Novo Nordisk) and the Humulin/Humalog pen (Eli Lilly) establish SoloStar as a state of the art pen that is suitable for most patients with diabetes. PMID- 17335414 TI - Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). AB - Targeted therapies for cancer is a rapidly advancing field, but the identification of tumor-specific ligands has proven difficult. Chlorotoxin (CTX) is a small, 36 amino acid neurotoxin isolated from the venom of the Giant Yellow Israeli scorpion Leiurus Quinquestriatus. Interestingly, the peptide has been found to preferentially bind to a variety of human malignancies, but shows little or no binding to normal human tissues. A synthetic version of this peptide (TM 601) has been manufactured and covalently linked to iodine 131 (131I-TM-601) as a means of targeting radiation to tumor cells. Preclinical studies and Phase I clinical trials have been completed in patients with recurrent glioma, a type of malignant brain tumor. These studies demonstrated that intracavitary dosing of 131I-TM-601 appears safe, minimally toxic, and binds malignant glioma with high affinity and for long durations. A Phase II trial of this agent using higher doses of radioactivity and repeated local administrations is underway. In addition, enrolment has begun in a Phase I trial evaluating whether systemically delivered 131I-TM-601 can be used to image metastatic solid tumors and primary gliomas. Due to its small size, selective tumor binding properties, minimal toxicity and relative ease of manipulation, CTX represents a potentially important targeting agent for many cancers. PMID- 17335416 TI - Diagnostic procedures and surgical treatment of craniodorsal coxofemoral luxation in calves. AB - OBJECTIVE: To report use of ultrasonographic examination of the coxofemoral joint, a surgical technique for repair of craniodorsal coxofemoral dislocation, and outcome. STUDY DESIGN: Clinical case reports. ANIMALS: Calves (n=4) with coxofemoral luxation. METHODS: Craniodorsal coxofemoral luxation was diagnosed by physical examination, radiographic, and ultrasonographic findings. Open surgical reduction of the femoral head was performed using a modified caudal approach. RESULTS: Craniodorsal luxation of the femoral head and the presence of an intact femoral neck were confirmed by ultrasonography. All luxations were successfully reduced and reluxation did not occur. At follow-up, 1 heifer had calved and 1 was 5 months pregnant. One calf died of bronchopneumonia 6 days after surgery. One calf had severe coxofemoral degenerative joint disease diagnosed (ultrasonography, radiography, and arthrocentesis) 3 months after surgery and confirmed by necropsy. CONCLUSION: Ultrasonography proved to be a simple and effective non-invasive technique for diagnosis of coxofemoral luxation. Immediate surgical intervention in hip dislocation in calves is necessary to avoid unnecessary trauma to subchondral structures. In calves, open instead of closed surgical reduction appears preferable because it allows access to the acetabular cavity for removal of debris. CLINICAL RELEVANCE: Ultrasonography should be considered a supplementary but not an alternative to radiographic examination for diagnosis of coxofemoral luxation and for follow-up examinations after reduction. PMID- 17335415 TI - Identification and localization of soluble sulfotransferases in the human gastrointestinal tract. AB - Soluble SULTs (sulfotransferases) are important in the regulation of messenger molecules and the elimination of xenobiotics. However, sulfo-conjugation of various substrates can also lead to the formation of reactive metabolites that may induce cancer and cause other damage. The aim of the present study was to identify the SULT forms expressed in the human gastrointestinal tract, especially the colon and rectum (common sites for cancer), and to determine their cellular localization. Normal colonic or rectal tissue, resected with tumours, was obtained from 39 subjects. For comparison, we additionally studied one to four samples from stomach, jejunum, ileum, cecum and liver. SULTs were detected by immunoblotting, immunohistochemistry and measurement of enzyme activities. SULT1A1, 1A3 and 1B1 were found in all parts of the gastrointestinal tract, often exceeding levels in liver (where these forms were present at high, undetectable and low levels respectively). They were predominantly localized in differentiated enterocytes. SULT1E1 and 2A1 were only detected in liver, jejunum, ileum and cecum. SULT1C1 was readily found in stomach, but was negligible elsewhere. SULT1A2 was present at low levels in individual samples. The remaining forms were not detected with the limitation that only high levels could be recognized with the antisera used. In conclusion, SULTs are abundant in the gastrointestinal tract of man. We suspect that they are involved in the presystemic elimination of bioactive food-borne components, including aglycones released by gut microbiota, as well as the bioactivation of some procarcinogens. PMID- 17335417 TI - Intraluminal tracheal stenting for treatment of tracheal narrowing in three cats. AB - OBJECTIVE: To describe the use of intraluminal tracheal stenting in 3 cats with either benign or malignant tracheal obstruction. STUDY DESIGN: Retrospective clinical study. ANIMALS: Three client-owned cats. METHODS: Medical records were reviewed and information regarding signalment, clinical signs, physical examination findings, diagnostic tests performed, treatment, outcome and follow up were retrieved. Intraluminal tracheal stent placement was performed as previously described in the literature. RESULTS: Three cats received intraluminal tracheal stents for the treatment of tracheal obstruction due to 3 different underlying causes: stricture secondary to traumatic endotracheal intubation, stricture secondary to a previous tracheotomy, and neoplasia. Self-expanding metallic stents of varying sizes were placed, and all cats recovered uneventfully from the procedures. The cat with tracheal neoplasia was euthanized because of pulmonary metastatic disease 6 weeks post-stent placement. The two cats with tracheal obstructions secondary to benign strictures are currently 39 months and 32 weeks post-stent placement, respectively. No complications were noted during the post-stent period in any of the 3 cats. CONCLUSIONS: Intraluminal tracheal stenting was easily, safely, and rapidly performed without complications and resulted in immediate improvement in clinical signs in all three cases. None of the cats in this study developed significant stent-associated complications during the study period. CLINICAL RELEVANCE: Intraluminal tracheal stenting has the potential to be a viable option for the treatment of tracheal obstruction in cats and perhaps for similar disease processes in other veterinary patients. PMID- 17335418 TI - Incidence of motion loss of the stifle joint in dogs with naturally occurring cranial cruciate ligament rupture surgically treated with tibial plateau leveling osteotomy: longitudinal clinical study of 412 cases. AB - OBJECTIVE: To report the incidence of loss of stifle extension or flexion and its relationship with clinical lameness after tibial plateau leveling osteotomy (TPLO) for treatment of cranial cruciate ligament (CCL) rupture. STUDY DESIGN: Longitudinal study. ANIMALS: Dogs (n=280) with CCL rupture (n=412). METHODS: TPLO was performed without meniscal release or arthrotomy. Angles of extension and flexion of the stifle were measured by goniometry to determine range of motion. Based upon motion loss, stifles were divided in 3 groups: no loss of extension or flexion (n=322), <10 degrees loss of extension or flexion (n=78), > or =10 degrees loss of extension or flexion (n=12). RESULTS: Loss of extension or flexion > or =10 degrees was associated with significantly (P=.001) higher clinical lameness scores in comparison with no loss, or loss of extension or flexion <10 degrees. Osteoarthrosis in the cranial femorotibial joint was significantly correlated (P<.005, r(2)=0.55) with loss of extension. Loss of extension > or =10 degrees was less tolerable and less amenable to physical rehabilitation than flexion loss. CONCLUSIONS: Loss of extension or flexion > or =10 degrees was responsible for higher clinical lameness scores. Osteoarthrosis in the cranial femorotibial joint led to extension loss. CLINICAL RELEVANCE: Loss of extension or flexion should be assessed in dogs with persistent clinical lameness after TPLO so that early intervention can occur. Our study provides guidelines to define clinically relevant loss of extension or flexion of stifle joint after TPLO. PMID- 17335419 TI - Recombinant human bone morphogenetic protein-2 in absorbable collagen sponge enhances bone healing of tibial osteotomies in dogs. AB - OBJECTIVE: To compare the efficacy of 2 doses of recombinant human bone morphogenetic protein-2 (rhBMP-2) on tibial osteotomy healing in dogs. STUDY DESIGN: Experimental, randomized complete block (n=7). ANIMALS: Adult female dogs (n=21). METHODS: Right midshaft tibial osteotomies were created and stabilized with a 1-mm gap using type I external fixators. Seven dogs were untreated controls and 14 with osteotomies were treated with either 0.05 or 0.2 mg/mL rhBMP 2 delivered in an absorbable collagen sponge (ACS). At 8 weeks, dogs were euthanatized and bones were mechanically tested and examined by microscopy. RESULTS: Bone healing based on radiographic scoring, was significantly improved in dogs treated with 0.2 mg/mL of rhBMP-2 compared with the other groups; these tibiae were also significantly stronger and stiffer than 0.05 mg/mL rhBMP-2 and control osteotomized tibiae. Histologic scores were significantly better for 0.2 mg/mL rhBMP-2 group than 0.05 mg/mL rhBMP-2 group, but neither was significantly different from control. CONCLUSIONS: rhBMP-2 in ACS at a concentration of 0.2 mg/mL improves healing of tibial osteotomies in dogs compared with untreated controls and 0.05 mg/mL rhBMP-2 based on force plate analysis and radiographic evaluation. This was not confirmed histologically but treated bones had improved mechanical properties at 8 weeks. CLINICAL RELEVANCE: After a long bone fracture, dogs may face a long recovery period before full return of limb function. rhBMP 2, in association with good fracture fixation principles, may enhance bone healing in dogs with diaphyseal fractures. PMID- 17335421 TI - Biomechanical comparison of dual interlocking single loop and double loop tension band techniques to the classic AO tension band technique for repair of olecranon osteotomies in dogs. AB - OBJECTIVE: To compare olecranon fragment stability between the classic tension band wire (TBW) technique with the wire placed either in contact with (Arbeitsgemeinschaft fur Osteosynthesefragen [AO]), or not in contact with, a Kirschner (K)-wire (AOW) to 2 novel wire patterns: a dual interlocking single loop (DISL) and a double loop (DL). STUDY DESIGN: Ex vivo mechanical evaluation on cadaveric bones. SAMPLE POPULATION: Canine ulnae (n=40) with olecranon osteotomies repaired with 2 K-wires and 1 of 4 TBW constructs. METHODS: Single load to failure applied through the triceps tendon. Displacement was measured from images captured from digital video. Techniques were compared based on the load resisted when the olecranon fragment was displaced 0.5, 1, and 2 mm. RESULTS: At 0.5 mm of displacement, the DISL construct resisted more load than the AOW construct (505 versus 350 N; P=.05). AO and DL constructs resisted an intermediate load (345 and 330 N, respectively). There was no significant difference between groups at 1 mm of displacement. At 2 mm of displacement, DL (785 N) resisted more load than AO (522 N, P=.01) and AOW (492 N, P=.03) groups. CONCLUSIONS: DISL constructs provided similar stability to classic TBW constructs whereas DL constructs were more stable at higher loads. CLINICAL RELEVANCE: The DL construct is easy to perform, less bulky, and provides comparable fragment stability to standard TBW techniques at functional loads. Surgical method is important for optimal performance of all TBW constructs. PMID- 17335420 TI - Clinical application of recombinant human bone morphogenetic protein-2 in 4 dogs. AB - OBJECTIVE: To describe outcome in dogs with insufficient bone healing treated with recombinant human bone morphogenetic protein-2 (rhBMP-2). STUDY DESIGN: Retrospective study. ANIMALS: Four dogs clinically affected with delayed union or nonunion bone healing. METHODS: Medical records were reviewed for signalment, clinical problem, treatment, and outcome. RESULTS: Four dogs that had delayed- or nonunion of bone fracture, osteotomy, or arthrodesis were treated with either minimally invasive, fluoroscopically guided, percutaneous administration or direct surgical application of rhBMP-2. Doses used ranged from 0.2 to 1.6 mg of rhBMP-2. In 3 dogs, a calcium phosphate matrix (CPM) carrier was used whereas in 1 dog commercially prepared rhBMP-2 impregnated in an absorbable collagen sponge (INFUSE Bone Graft) was used. This latter dog had osteomyelitis associated with implant infection before rhBMP-2 administration. Rapid radiographic union was noted in all dogs with excellent long-term outcome. Adverse effects were minimal and included transient worsening of lameness after percutaneous administration of rhBMP-2 in 2 dogs. CONCLUSIONS: rhBMP-2 stimulated rapid bone formation at delayed- or nonunion sites resulting in radiographic bone union with minimal adverse effects and excellent long-term outcome in 4 dogs. CLINICAL RELEVANCE: Direct intraoperative administration or fluoroscopically guided, minimally invasive delivery of rhBMP-2 may be an effective treatment modality for bone delayed- or nonunions and could potentially be used to stimulate new bone production in a variety of orthopedic surgical conditions in dogs. PMID- 17335422 TI - Endoscopic resection of dorsal spinous processes and interspinous ligament in ten horses. AB - OBJECTIVE: To describe endoscopic surgical subtotal resection of the dorsal spinous processes (DSP) and interspinous ligament in horses. STUDY DESIGN: Descriptive clinical study. ANIMALS: Adult horses (n=10) with back pain and impinging dorsal spinous processes METHODS: Diseased portions of DSP and interspinous ligament were resected by endoscopic surgery, using Destandau Endospine to create a surgical space and provide triangulation for the endoscope, suction cannula, and surgical instruments. Medical records of 10 horses with pain attributable to DSP pathology treated by endoscopic resection of DSP were reviewed to determine intra- and postoperative complications and outcome. RESULTS: Affected portions of DSP were successfully resected with minimal hemorrhage. Limited periosteal reaction was noticed after 3 months in 2 horses. Nine horses had no complications and returned to full work within 8 weeks; 1 developed a subcutaneous abscess, which was successfully managed, and returned to work after 3 months. Surgical resection improved presenting clinical signs and owner's complaint although 2 horses did not return to previous performance levels. CONCLUSION: Resection of DSP and interspinous ligament can be successfully performed endoscopically in horses. Hemorrhage was minimal but reduced visibility. Complications were minimal and most horses returned to work by 8 weeks. CLINICAL RELEVANCE: Endoscopic resection of DSP is a safe and reliable surgical procedure in horses. PMID- 17335423 TI - In vitro comparison of tibial plateau leveling osteotomy with and without use of a tibial plateau leveling jig. AB - OBJECTIVE: To evaluate the influence of a tibial plateau leveling jig on osteotomy orientation, fragment reduction, and postoperative tibial plateau angle (TPA) during tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: In vitro experimental study. ANIMALS: Large-breed canine cadavers (n=20). METHODS: TPLO was performed on 40 hindlimbs using 4 methods. Group 1: Jig; dogs in dorsal recumbency with the osteotomy parallel to the distal jig pin. Groups 2-4: No jig; dogs in lateral recumbency with the osteotomy in a vertical orientation (group 2: tibia parallel to the table top; group 3: controlled superimposition of the femoral condyles; group 4: internal rotation of the tibia). Postoperative TPA, fragment reduction, and osteotomy orientation relative to the tibial plateau were compared. Positive or negative values denoted deviation from parallel relative to the tibial plateau. RESULTS: Postoperative TPA, fragment reduction, and proximodistal osteotomy orientation were not significantly different between groups. Craniocaudal osteotomy orientation was significantly different (P<.005) from the tibial plateau. Median deviations were -4.0 degrees (group 1), 11.8 degrees (group 2), 11.2 degrees (group 3), and 0.2 degrees (group 4). Group 1 was not significantly different from group 4. CONCLUSIONS: A jig is not essential for osteotomy orientation, tibial plateau rotation, or fragment reduction. Comparable results were achieved performing a vertical osteotomy with the tibia slightly internally rotated (10 degrees -15 degrees) and parallel to the table surface. CLINICAL RELEVANCE: TPLO without use of a jig reduces surgical trauma, is less time consuming, and reduces cost. PMID- 17335424 TI - Repair of oronasal fistulae using auricular cartilage grafts in five cats. AB - OBJECTIVE: To describe repair of chronic palatine defects in cats, with free cartilage graft harvested from either the pinna (scapha) or vertical ear canal (annular cartilage). STUDY DESIGN: Retrospective study. ANIMALS: Cats (n=5) with chronic oronasal fistula. METHODS: Cartilage was harvested from either the scapha or annular cartilage and epithelium removed. After preparation of the edges of the palatal defect by separation of the oral and palatal mucosa circumferentially, the graft was inserted between the epithelial layers and secured without tension. The graft acted as a scaffold for migration of granulation tissue and epithelialization. RESULTS: Oronasal fistulae were successfully repaired in 5 cats (3 pinna grafts; 2 annular cartilage grafts); 1 cat required a second graft after the first graft was dislodged. CONCLUSIONS: Auricular cartilage provides a reliable framework for repair of oronasal fistulae in cats. CLINICAL RELEVANCE: Chronic oronasal fistulae refractory to conventional repair can be treated by use of auricular free graft (pinna or annular cartilage) without disfigurement. Use of annular cartilage to support palatal repairs offers surgeons an additional option when other methods have failed. We recommend using conchal cartilage as the initial treatment approach for repair of small oronasal fistulae in cats. PMID- 17335425 TI - Effect of tibial tuberosity advancement on cranial tibial subluxation in canine cranial cruciate-deficient stifle joints: an in vitro experimental study. AB - OBJECTIVE: To evaluate the effect of tibial tuberosity advancement (TTA) on tibiofemoral shear force as reflected by measurement of cranial tibial subluxation (CTS) and patella tendon angle (PTA) in the canine cranial cruciate ligament (CrCL) deficient stifle joint. STUDY DESIGN: In vitro cadaver study. ANIMALS: Canine cadaveric hind limbs (n=10). METHODS: CTS and PTA were evaluated from lateral radiographic projections in axially loaded intact CrCL stifle joints, after transection of the CrCL, at a maximally advanced tibial tuberosity position, and at a critical point position. A custom-designed hinge plate allowed alteration of the tibia to tibial tuberosity distance (Ti-TT) under axial load. Digitized radiographic images were used to quantify CTS, PTA, and Ti-TT. Comparisons within groups were made using 1-way repeated measures ANOVA. A post hoc Tukey's HSD test was used to determine post-ANOVA pair-wise comparison within these groups. Significance was set at a value of P<.05. RESULTS: CTS occurred after CrCL transection, which was significantly different from the intact position (P<.01). Subsequent stability of the stifle joint was obtained by advancing the tibial tuberosity. In the maximally advanced tibial tuberosity position, caudal tibial thrust was generated resulting in caudal tibial subluxation that was significantly different from the transected CrCL position (P<.01) and from the intact CrCL position (P<.01). Despite a stable joint, there was slight CTS at the critical point position, which was significantly different from the intact CrCL position (P<.05). The PTA at the maximally advanced position was significantly different from the intact, critical point and reference 90 degrees PTAs (P<.01). The PTA at the critical point position was significantly different from the intact and maximally advanced tibial tuberosity PTAs (P<.01), but not different (P>.05) from the reference 90 degrees PTA. CONCLUSION: We demonstrated that advancement of the tibial tuberosity neutralized cranial tibial thrust, and converted cranial tibial thrust into caudal tibial thrust. Neutralization of tibiofemoral shear forces occurred at a PTA of 90.3+/-9.0 degrees. CLINICAL RELEVANCE: TTA can effectively change the magnitude and direction of the tibiofemoral shear force, and thus may be used to prevent craniotibial translation in a CrCL deficient stifle joint. PMID- 17335426 TI - Clinical evaluation of a titanium, headless variable-pitched tapered cannulated compression screw for repair of frontal plane slab fractures of the third carpal bone in thoroughbred racehorses. AB - OBJECTIVE: To report clinical evaluation of third carpal bone (C3) frontal plane slab fracture repair with the Acutrak screw system. STUDY DESIGN: Prospective case series. SAMPLE POPULATION: Racing Thoroughbreds (n=17) with frontal C3 slab fractures. METHODS: C3 slab fractures in Thoroughbred racehorses (1999-2004) were repaired by use of the Acutrak screw system. Data collected were (1) preoperative variables--gender, age at injury, limb involved, injury occurrence, fracture thickness, complexity, and displacement, race starts and earnings and (2) postoperative variables were: surgical complications, days to first start, race starts, and earnings. A Wilcoxon signed-rank test was used to compare pre- and postoperative starts and earnings; significance was set at P<.05. RESULTS: Seventeen Thoroughbred racehorses (12 females, 3 males, 2 geldings) were enrolled. Mean (+/-SD) age at injury was 3.3+/-1.0 years. Right carpi (10) were affected more than left (7). Ten injuries occurred during training, 7 during racing. Twelve of 15 horses that raced before injury returned to racing. Average days to first start was 349.3+/-153.9 days. Horses that returned to racing had more starts after repair (median, 6.5 versus 3.5; P=.04) and did not have decreased earnings per start (median, $2452 versus $3061; P=.30). CONCLUSION: The Acutrak screw system is a useful repair technique for frontal C3 slab fractures in Thoroughbred racehorses. CLINICAL RELEVANCE: Adequate reduction and stability of C3 slab fractures can be achieved with the Acutrak screw system, decreasing the likelihood of fragment splitting and screw head impingement on carpal soft tissues. PMID- 17335428 TI - Unifying principles of regeneration I: Epimorphosis versus morphallaxis. AB - Because research on regeneration has a long history, some classic definitions and concepts about regeneration which were established in earlier times have been retained without reconsideration for a long time, even though many relevant new findings have accumulated. To clarify the points on which research should be focused on for elucidating the mechanisms of regeneration, we should reconsider such classical definitions and principles of regeneration at the cellular and molecular level. Here, we consider two differing principles of regeneration which have been classically defined as 'epimorphosis' and 'morphallaxis', and propose the abandonment of these classical categories and their replacement by a new unifying principle in order to facilitate regeneration studies. PMID- 17335429 TI - Involvement of canonical Wnt/Wingless signaling in the determination of the positional values within the leg segment of the cricket Gryllus bimaculatus. AB - The cricket Gryllus bimaculatus is a hemimetabolous insect whose nymphs possess the ability to regenerate amputated legs. Previously, we showed that Gryllus orthologues of Drosophila hedgehog (Gb'hh), wingless (Gb'wg) and decapentaplegic (Gb'dpp) are expressed during leg regeneration and play essential roles in the establishment of the proximal-distal axis. Here, we examined their roles during intercalary regeneration: when a distally amputated tibia with disparate positional values is placed next to a proximally amputated host, intercalary growth occurs in order to regenerate the missing part. In this process, we examined expression patterns of Gb'hh and Gb'wg. We found that expressions of Gb'hh and Gb'wg were induced in a regenerate and the host proximal to the amputated region, but not in the grafted donor distal to the regenerate. This directional induction occurs even in the reversed intercalation. Because these results are consistent with a distal-to-proximal respecification of the regenerate, Gb'wg may be involved in the re-establishment of the positional values in the regenerate. Furthermore, we found that no regeneration occurs when Gb'armadillo (the orthologue of beta-catenin) was knocked down by RNA interference. These results indicate that the canonical Wnt/Wingless signaling pathway is involved in the process of leg regeneration and determination of positional information in the leg segment. PMID- 17335430 TI - Regeneration potency of mouse limbs. AB - Mammalians have a low potency for limb regeneration compared to that of amphibians. One explanation for the low potency is the deficiency of cells for regenerating amputated limbs in mammals. Amphibians can form a blastema with dedifferentiated cells, but mammals have few such cells. In this paper, we report limb formation, especially bone/cartilage formation in amputated limbs, because bone/cartilage formation is a basic step in limb pattern regeneration. After the amputation of limbs of a neonatal mouse, hypertrophy of the stump bone was observed at the amputation site, which was preceded by cell proliferation and cartilage formation. However, no new elements of bone/cartilage were formed. Thus, we grafted limb buds of mouse embryo into amputated limbs of neonatal mice. When the intact limb bud of a transgenic green fluorescent protein (GFP) mouse was grafted to the limb stump after amputation at the digit joint level, the grafted limb bud grew and differentiated into bone, cartilage and soft tissues, and it formed a segmented pattern that was constituted by bone and cartilage. The skeletal pattern was more complicated when limb buds at advanced stages were used. To examine if the grafted limb bud autonomously develops a limb or interacts with stump tissue to form a limb, the limb bud was dissociated into single cells and reaggregated before grafting. The reaggregated limb bud cells formed similar digit-like bone/cartilage structures. The reaggregated grafts also formed segmented cartilage. When the reaggregates of bone marrow mesenchymal cells were grafted into the stump, these cells formed cartilage, as do limb bud cells. Finally, to examine the potency of new bone formation in the stump tissue without exogenously supplied cells, we grafted gelatin gel containing BMP-7. BMP induced formation of several new bone elements, which was preceded by cartilage formation. The results suggest that the environmental tissues of the stump allow the formation of cartilage and bone at least partially, and that limb formation will be possible by supplying competent cells endogenously or exogenously in the future. PMID- 17335431 TI - Regeneration of the amphibian intestinal epithelium under the control of stem cell niche. AB - The epithelium of the mammalian digestive tract originates from stem cells and undergoes rapid cell-renewal throughout adulthood. It has been proposed that the microenvironment around the stem cells, called 'niche', plays an important role in epithelial cell-renewal through cell-cell and cell-extracellular matrix interactions. The amphibian intestine, which establishes epithelial cell-renewal during metamorphosis, serves as a unique and good model for studying molecular mechanisms of the stem cell niche. By using the organ culture of the Xenopus laevis intestine, we have previously shown that larval-to-adult epithelial remodeling can be organ-autonomously induced by thyroid hormone (TH) and needs interactions with the surrounding connective tissue. Thus, in this animal model, the functional analysis of TH response genes is useful for clarifying the epithelial-connective tissue interactions essential for intestinal remodeling at the molecular level. Recent progress in culture and transgenic technology now enables us to investigate functions of such TH response genes in the X. laevis intestine and sheds light on molecular aspects of the stem cell niche that are common to the mammalian intestine. PMID- 17335432 TI - Regeneration of the amphibian retina: role of tissue interaction and related signaling molecules on RPE transdifferentiation. AB - Regeneration of eye tissue is one of the classic subjects in developmental biology and it is now being vigorously studied to reveal the cellular and molecular mechanisms involved. Although many experimental animal models have been studied, there may be a common basic mechanism that governs retinal regeneration. This can also control ocular development, suggesting the existence of a common principle between the development and regeneration of eye tissues. This notion is now becoming more widely accepted by recent studies on the genetic regulation of ocular development. Retinal regeneration can take place in a variety of vertebrates including fish, amphibians and birds. The newt, however, has been considered to be the sole animal that can regenerate the whole retina after the complete removal of the retina. We recently discovered that the anuran amphibian also retains a similar ability in the mature stage, suggesting the possibility that such a potential could be found in other animal species. In the present review article, retinal regeneration of amphibians (the newt and Xenopus laevis) and avian embryos are described, with a particular focus on transdifferentiation of retinal pigmented epithelium. One of the recent progresses in this field is the availability of tissue culture methods to analyze the initial process of transdifferentiation, and this enables us to compare the proliferation and neural differentiation of retinal pigmented epithelial cells from various animal species under the same conditions. It was revealed that tissue interactions between the retinal pigmented epithelium and underlying connective tissues (the choroid) play a substantial role in transdifferentiation and that this is mediated by a diffusible signal such as fibroblast growth factor 2. We propose that tissue interaction, particularly mesenchyme-neuroepithelial interaction, is considered to play a fundamental role both in retinal development and regeneration. PMID- 17335433 TI - Brain regeneration in anuran amphibians. AB - Urodele amphibians are highly regenerative animals. After partial removal of the brain in urodeles, ependymal cells around the wound surface proliferate, differentiate into neurons and glias and finally regenerate the lost tissue. In contrast to urodeles, this type of brain regeneration is restricted only to the larval stages in anuran amphibians (frogs). In adult frogs, whereas ependymal cells proliferate in response to brain injury, they cannot migrate and close the wound surface, resulting in the failure of regeneration. Therefore frogs, in particular Xenopus, provide us with at least two modes to study brain regeneration. One is to study normal regeneration by using regenerative larvae. In this type of study, the requirement of reconnection between a regenerating brain and sensory neurons was demonstrated. Functional restoration of a regenerated telencephalon was also easily evaluated because Xenopus shows simple responses to the stimulus of a food odor. The other mode is to compare regenerative larvae and non-regenerative adults. By using this mode, it is suggested that there are regeneration-competent cells even in the non regenerative adult brain, and that immobility of those cells might cause the failure of regeneration. Here we review studies that have led to these conclusions. PMID- 17335434 TI - Expression of matrix metalloproteinase genes in regressing or remodeling organs during amphibian metamorphosis. AB - Several matrix metalloproteinases (MMP) are induced by thyroid hormone (TH) during the climax of amphibian metamorphosis and play a pivotal role in the remodeling of the intestine and the regressing tail and gills by degrading the extracellular matrix (ECM). We compared MMP gene expression levels precisely by quantitative real-time reverse transcription-polymerase chain reaction. The expression of MMP genes increases prominently at Nieuwkoop and Faber (NF) stages 60, 60-61 and 62 in the intestine, gills and tail, respectively, when the drastic morphological changes start in each organ. Gene expression analysis in the TH treated tadpoles and cell line revealed that MMP mRNAs are upregulated in response to TH quickly within several hours to low levels and then increase in a day to high levels. All TH-induced MMP genes have TH response elements (TREs). The presence of high affinity TREs in MMP genes correlates with early TH induction. Based on these results, we propose that TH stimulates the transcription of MMP genes through TREs within several hours to low levels and then brings about the main increase of mRNAs by TH-induced transcriptional factors, including TH receptor beta, in a cell type-specific transcriptional environment. PMID- 17335435 TI - Cellular and molecular processes of regeneration, with special emphasis on fish fins. AB - The phenomenon of 'epimorphic regeneration', a complete reformation of lost tissues and organs from adult differentiated cells, has been fascinating many biologists for many years. While most vertebrate species including humans do not have a remarkable ability for regeneration, the lower vertebrates such as urodeles and fish have exceptionally high regeneration abilities. In particular, the teleost fish has a high ability to regenerate a variety of tissues and organs including scales, muscles, spinal cord and heart among vertebrate species. Hence, an understanding of the regeneration mechanism in teleosts will provide an essential knowledge base for rational approaches to tissue and organ regeneration in mammals. In the last decade, small teleost fish such as the zebrafish and medaka have emerged as powerful animal models in which a variety of developmental, genetic and molecular approaches are applicable. In addition, rapid progress in the development of genome resources such as expressed sequence tags and genome sequences has accelerated the speed of the molecular analysis of regeneration. This review summarizes the current status of our understanding of the cellular and molecular basis of regeneration, particularly that regarding fish fins. PMID- 17335436 TI - Tail regeneration in the Xenopus tadpole. AB - The tail of the Xenopus tadpole contains major axial structures, including a spinal cord, notochord and myotomes, and regenerates within 2 weeks following amputation. The tail regeneration in Xenopus can provide insights into the molecular basis of the regeneration mechanism. The regenerated tail has some differences from the normal tail, including an immature spinal cord and incomplete segmentation of the muscle masses. Lineage analyses have suggested that the tail tissues are reconstructed with lineage-restricted stem cells derived from their own tissues in clear contrast to urodele regeneration, in which multipotent blastema cells derived from differentiated cells play a major role. Comprehensive gene expression analyses resulted in the identification of a panel of genes involved in sequential steps of the regeneration. Manipulation of genes' activities suggested that the tail regeneration is regulated through several major signaling pathways. PMID- 17335437 TI - Liver development and regeneration: from laboratory study to clinical therapy. AB - The liver has an unusual capacity to regenerate after a loss of mass and function caused by surgical resection or toxic liver injury. Over the last 10 years there have been major advances in our understanding of the molecular and cellular mechanisms underlying liver development and regeneration. The numerous factors crucial to these phenomena have been identified mainly by using knockout mice. Forward-genetics studies using zebrafish and medaka have also generated many mutants with liver disorders or defects in liver formation. Our goal is to translate knowledge gained from laboratory work and animal models into novel therapies for human liver diseases. Exciting progress has been achieved using human partial liver transplantation and autologous cell therapy. PMID- 17335438 TI - Growth potential of adult hepatocytes in mammals: highly replicative small hepatocytes with liver progenitor-like traits. AB - The liver is one of the few organs that is capable of completely regenerating itself without using a stem cell population. When damaged, growth factors and cytokines are released, stimulating terminally differentiated adult hepatocytes and making them re-enter the cell cycle. We have been developing a series of studies on the growth potential of rat and human hepatocytes to identify a population of hepatocytes that is responsible for the regeneration of the injured liver. For this purpose, we established an appropriate culture method for hepatocytes by which growth and differentiation capacities are practically examined under various experimental conditions. This in vitro assay system allows us to identify small hepatocytes that are prominently replicative compared to large hepatocytes. Non-parenchymal cells play critical roles in the proliferation of small hepatocytes. These hepatocytes are present in both rat and human liver and are located in portal regions there. Phenotypic features were examined at morphological and gene/protein levels in detail, which showed the phenotypic plasticity in vitro. Mammalian liver includes a population of small hepatocytes in normal adults with a minute occupancy rate. We speculate that small hepatocytes play a role in regenerating the injured liver and in compensating for apoptotic hepatocytes in the physiological turnover of hepatocytes. PMID- 17335439 TI - PRO: Endoscopy is necessary before treating Helicobacter pylori in patients with dyspepsia. PMID- 17335440 TI - CON: Endoscopy is not necessary before treating Helicobacter pylori in patients with uncomplicated dyspepsia. PMID- 17335441 TI - A BALANCING VIEW: Endoscopy in dyspepsia: a tale of two cities. PMID- 17335442 TI - International comparisons of manpower in gastroenterology. AB - Health-care systems vary among countries and we were interested in how this might impact on gastroenterology manpower. We assessed the number of gastroenterologists in Canada and compared this with four countries where data were available over the Internet in either French or English. The number of gastroenterologists per 100,000 of the population was 3.9 in the United States, 3.48 in France, 2.1 in Australia, 1.83 in Canada, and 1.41 in the U.K. This variation in number of gastroenterologists was not reflected in the overall number of specialists per 100,000, which was similar in all five countries. Furthermore, the difference in gastroenterology manpower did not correlate with the amount of gross domestic product spent on health care. Countries with a low number of gastroenterologists per 100,000 all had a strong primary-care gatekeeper system, although this observation may be coincidental, as only five countries were studied. Canada had the most equitable distribution of gastroenterologists across the country with only modest differences among provinces. The United States had the most variation in the number of gastroenterologists per 100,000 of the population among states. PMID- 17335443 TI - A patient's perspective: my battle with Crohn's disease. PMID- 17335444 TI - Extent of low-grade dysplasia in Barrett's esophagus: is it useful for risk stratification? AB - Low-grade dysplasia remains one of the great enigmas of Barrett's esophagus. Limited information is available on the natural history of this lesion, and studies suggest that cancer risk in patients with low-grade dysplasia is intermediate between that of intestinal metaplasia without dysplasia and high grade dysplasia. Natural history studies of low-grade dysplasia are hampered by problems with interobserver variability among pathologists and sampling variability among endoscopists. To date, the extent of low-grade dysplasia has not been examined as a potential risk factor for the subsequent development of adenocarcinoma. Srivastava et al., in this issue of the American Journal of Gastroenterology, found that the extent of low-grade dysplasia, as measured by several different methods, was a risk factor for progression to cancer. While these findings are novel and provocative, it is premature to request your pathologist to count the number of crypts or biopsies with low-grade dysplasia just yet. However, these findings, if confirmed by studies utilizing a simpler measure of the extent of low-grade dysplasia, may help us determine the prognostic significance of this lesion in the future. PMID- 17335445 TI - Endoscopic treatment of external pancreatic fistulas: when draining the main pancreatic duct is not enough. AB - OBJECTIVES: Transpapillary drainage of the main pancreatic duct (MPD) has been proposed for the treatment of external pancreatic fistulas (EPF) but may not suffice to treat complex cases. The aim of the present study was to explore the efficacy of various endoscopic or combined percutaneous and endoscopic techniques in the treatment of EPFs. METHODS: Sixteen patients presenting with EPFs were treated in our department. The techniques applied and patients' clinical outcome are described. RESULTS: All but three patients underwent transpapillary MPD drainage by pancreatic sphincterotomy (N = 13). Additional endoscopic procedures performed were: (a) pancreatic fluid collection (PFC) drainage (N = 5), (b) transmural drainage between the fistula path and the gastrointestinal (GI) tract (N = 5), and (c) endoscopic ultrasound (EUS)-guided pancreaticoduodenostomy because of complete pancreatic duct rupture (N = 1). Fistula closure was achieved in all patients except one, who required surgery. During a median follow-up period of 18 months (range 6-52) three patients had fistula recurrence, and two, PFC recurrence. Both conditions were cured successfully by repeated endoscopic therapy. All recurrences occurred within 3 months of initial successful treatment. CONCLUSIONS: Combined endoscopic and percutaneous treatment appears to be safe and effective for the management of complex cases of EPFs. PMID- 17335446 TI - Endotherapy for pancreatic fistulae: inside out or outside in? AB - How therapeutic endoscopy has changed! As participants and observers of the evolution of endotherapy, one has to marvel at the progress we have made in this field. We have withstood mild outrage of our description of precut sphincterotomy, to questions regarding the efficacy of balloon dilators for the bile and pancreatic duct sphincters, to outspoken objections at national meetings of our presentations describing the use of pancreatic stents for the treatment of various forms of pancreatitis, to the expectation of greater progress and advancement in the field. We routinely drain pseudocysts, stent disrupted pancreatic ducts, but, now, we commend the innovators from Erasme Hospital in Brussels for their newly described technique of completing an endoscopic rendezvous procedure performed through an external pancreatic fistula (EPF). In this new technique, an endoscopist, who is observing the progress of a percutaneous puncture through an EPF, positions an endoscope in the stomach or small bowel lumen while assisting another endoscopist (not a radiologist) who is advancing catheters and guide wires through the fistulous tract (a virtual cyst demonstrated by EUS) so that the assistant can guide the operator's puncture through the gut wall into the bowel lumen in order to deploy an internal stent to allow the normal flow or egress of pancreatic juices into the gut facilitating the closure of the fistula. Although the procedure is time-consuming and probably not cost-effective for the free enterprise reimbursement system in the United States, the results of this procedure, in a small number of patients over a long time period, were as effective as surgery. Our hats are off to those who continue to explore the outer limits of endotherapy, and we look forward to more exciting, unquestioned developments in the field. This is progress. PMID- 17335447 TI - Small bowel endoscopy: have we conquered the final frontier? AB - With a functional instrument channel and the capacity to visualize most of the small bowel, the true value of the DBE is finally being realized. The current issue of The American Journal of Gastroenterology features an article that summarizes the therapeutic experience of double-balloon enteroscopy (DBE) by Andrea May and colleagues. Virtually all therapeutic devices used with the conventional endoscopes are now available for use through the DBE scopes. Polypectomy, hemostasis therapy, intestinal stenting, foreign body removal, mucosectomy, direct jejunostomy, and ERCP in Roux-en-Y anatomy are now all realistically possible to perform. But behind the very positive data are many technical problems that the authors and those interested in performing DBE have to overcome. Passage of accessories is difficult through the small working channel. Approaching a lesion from a proper angle is a particularly daunting task when the endoscope is situated in the deeper parts of the intestine. The current report of 3.4% of severe complications is well within the range reported previously and is acceptable in light of potential problems encountered with alternative treatment modalities. An important observation of these authors is the particularly high rate of complication associated with polypectomy. Now that we have established the strong diagnostic and therapeutic values of DBE, we need to make it more available and safer for our patients. PMID- 17335448 TI - Epidemiology and prognostic determinants of patients with bacteremic cholecystitis or cholangitis. AB - OBJECTIVES: To compare mortalities in patients with sepsis due to biliary tract infections (BTIs) and due to infections from other sources, and to identify independent predictors of mortality in these patients. METHODS: This study was part of a community-acquired bloodstream infection (BSI) study that prospectively collected comprehensive clinical, laboratory, and outcome data from 937 consecutive patients with microbiologically documented BSI in the emergency department. BTI was the confirmed source of 145 of the 937 BSIs. We determined the independent prognostic factors by evaluating the correlation between 30-day mortality and various factors, for example, comorbidity, clinical severity, related hepatobiliary complication, and decompressive procedures. RESULTS: Patients with biliary sepsis had a high percentage of Gram-negative (88.3%), polymicrobial (26.9%), and anaerobic infections (6.9%). The 30-day overall mortality was 11.7%. Cox proportional hazard regression analysis disclosed five significant independent predictors: acute renal failure (hazard ratio, 95% confidence interval: 6.86, 6.02-25.5), septic shock (5.83, 4.36-15.64), malignant obstruction (4.35, 1.89-12.96), direct type hyperbilirubinemia (1.26, 1.1-1.42), and Charlson score > or =6 (1.57, 1.12-2.22). Compared with the remaining 792 patients in the source population, patients with bacteremic BTI had significantly better prognosis (log-rank test, P= 0.007). Adjusting for age, comorbidity, and clinical severity, BTI was still independently associated with better 30-day survival (0.25-0.76). CONCLUSIONS: Though the mortality rate in patients with bacteremic BTI is substantial, survival is better than in those with bacteremia from other sources. The main prognostic factors identified in this study may help clinicians recognize patients at high risk for early mortality so that they can give prompt, appropriate treatment. PMID- 17335449 TI - New studies on the role of smoking in inflammatory bowel disease: are we not beating a dead horse? AB - The role of smoking in inflammatory bowel disease (IBD) has drawn more interest as our understanding of these diseases has moved beyond the simple designations of Crohn's disease (CD) and ulcerative colitis (UC). In this issue of the journal, Aldous et al. present two papers on the role of smoking in the heterogeneity of IBD. They confirm the findings of many, are at odds with the findings of some, and provide novel observations for us all as we try to understand this complex interaction. Do these studies provide more clarity or just add to the noise? As always, the devil is in the details. PMID- 17335450 TI - ACG practice guidelines: esophageal reflux testing. AB - Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Issues regarding the utilization of conventional, catheter-based pH monitoring are discussed. Improvements in the interpretation of esophageal pH recordings through the use of symptom-reflux association analyses as well as limitations gleaned from recent studies are reviewed. The clinical utility of pH recordings in the proximal esophagus and stomach is examined. Newly introduced techniques of duodenogastroesophageal reflux, wireless pH capsule monitoring and esophageal impedance testing are assessed and put into the context of traditional methodology. Finally, recommendations on the clinical applications of esophageal reflux testing are presented. PMID- 17335452 TI - Bispectral index monitoring of sedation during endoscopy: buried alive? PMID- 17335454 TI - Response to Robert E. Kravetz. PMID- 17335455 TI - Stomal bile leakage following percutaneous endoscopic gastrostomy treated with a simple technique. PMID- 17335456 TI - Successful treatment of a Crohn's disease patient infected with bacteremic Mycobacterium paratuberculosis. PMID- 17335457 TI - Reversible dysgeusia attributed to azathioprine. PMID- 17335458 TI - IgG4-related sclerosing cholangitis should be included as an exclusion criterion for the diagnosis of primary sclerosing cholangitis. PMID- 17335459 TI - Is diabetes mellitus or obesity a more important risk factor for colonic adenoma? PMID- 17335463 TI - Low HDL-cholesterol is common in European Type 2 diabetic patients receiving treatment for dyslipidaemia: data from a pan-European survey. AB - AIMS: To measure the prevalence of low high-density lipoprotein (HDL)-cholesterol (men < 1.03 mmol/l; women < 1.29 mmol/l) in European Type 2 diabetic patients receiving treatment for dyslipidaemia. METHODS: The pan-European Survey of HDL cholesterol measured lipids and other cardiovascular risk factors in 3866 patients with Type 2 diabetes and 4436 non-diabetic patients undergoing treatment for dyslipidaemia in 11 European countries. RESULTS: Diabetic patients were more likely to be obese or hypertensive than non-diabetic patients. Most patients received lifestyle interventions (87%) and/or a statin (89%); treatment patterns were similar between groups. Diabetic patients had [means (SD)] lower HDL cholesterol [1.22 (0.37) vs. 1.35 mmol/l (0.44) vs. non-diabetic patients, P < 0.001] and higher triglycerides [2.32 (2.10) vs. 1.85 mmol/l (1.60), P < 0.001]. More diabetic vs. non-diabetic patients had low HDL-cholesterol (45% vs. 30%), high triglycerides (> or = 1.7 mmol/l; 57% vs. 42%) or both (32% vs. 19%). HDL cholesterol < 0.9 mmol/l was observed in 18% of diabetic and 12% of non-diabetic subjects. Differences between diabetic and non-diabetic groups were slightly greater for women. LDL- and total cholesterol were lower in the diabetic group [3.02 (1.05) vs. 3.30 mmol/l (1.14) and 5.12 (1.32) vs. 5.38 mmol/l (1.34), respectively, P < 0.001 for each]. CONCLUSIONS: Low HDL-cholesterol is common in diabetes: one in two diabetic women has low HDL-cholesterol and one diabetic man in four has very low HDL-cholesterol. Management strategies should include correction of low HDL-cholesterol to optimize cardiovascular risk in diabetes. PMID- 17335464 TI - Maternal glycated haemoglobin, pre-gestational weight, pregnancy weight gain and risk of large-for-gestational-age babies: a Danish cohort study of 209 singleton Type 1 diabetic pregnancies. AB - AIMS: To examine the association between maternal glycated haemoglobin in the second half of diabetic pregnancies and the relative risk of delivering large-for gestational-age (LGA) babies, controlling for maternal body mass index (BMI) before pregnancy, weight gain, age, White class and smoking habits. METHODS: We identified all pregnant diabetic women in North Jutland County, Denmark from 1985 to 2003. Data on HbA(1c) values from the 20th gestational week to term were collected from medical records and the babies were classified as large, normal or small for gestational age. The association between glycated haemoglobin (HbA(1c)) and relative risk of delivering an LGA baby was quantified based on logistic regression models and stratified analysis controlling for the five covariates. RESULTS: We included 209 singleton pregnancies with assessable HbA(1c) values of which 59%[95% confidence interval (CI) 52-65%] terminated with an LGA baby. Increasing levels of HbA(1c), BMI and weight gain were all associated with increasing risk of delivering an LGA baby. Analyses stratified according to maternal BMI showed that the association between HbA(1c) and risk of delivering an LGA baby was restricted to pregnancies with pre-pregnancy BMI > 23 kg/m(2). We found no association between HbA(1c) and risk of delivering an LGA baby in pregnancies with lower BMI. CONCLUSION: The positive association between glycated haemoglobin and birth of an LGA baby seems to be restricted to women with BMI > 23 kg/m(2). PMID- 17335465 TI - Randomized double-blind study comparing the efficacy and safety of lamotrigine and amitriptyline in painful diabetic neuropathy. AB - AIMS: To compare the efficacy and safety of lamotrigine and amitriptyline in controlling chronic painful peripheral neuropathy in diabetic patients. METHODS: A randomized, double-blind, crossover, active-control, clinical trial with variable dose titration was carried out (n = 53). Amitriptyline orally, at doses of 10, 25 and 50 mg at night-time, each dose for 2 weeks, and lamotrigine orally, at doses of 25, 50 and 100 mg twice daily, each dose for 2 weeks, by optional titration were used. There was a placebo washout period for 2 weeks between the two drugs. Assessment for pain relief, overall improvement and adverse events were carried out. RESULTS: Good, moderate and mild pain relief were noted in 19 (41%), six (13%) and seven (15%) patients on lamotrigine and 13 (28%), five (11%) and 15 (33%) patients on amitriptyline, respectively, by patient's global assessment of efficacy and safety. Patient and physicians global assessment, McGill pain questionnaire and Likert pain scale showed no significant difference between the treatments, although improvement with both treatments was seen from 2 weeks. Of the 44 adverse events reported, 33 (75%) were with amitriptyline, sedation being the commonest [in 19 (43%) patients]. Lamotrigine caused adverse events in 11 (25%), of which rash in three (7%) and elevations of creatinine in four (9%) were the most common. The preferred lamotrigine dose was 25 mg twice daily. CONCLUSIONS: As there are few differences between the two treatments in efficacy, lamotrigine 25 mg twice daily might be the first choice as it is associated with fewer adverse effects in our population. PMID- 17335466 TI - Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with Type 2 diabetes in UK primary care. AB - AIMS: To describe initial achievement of glycaemic targets and subsequent hyperglycaemia in patients with Type 2 diabetes managed with oral agent monotherapy in UK primary care from 1998 to 2004. METHODS: Electronic medical records of patients initiating metformin (n = 3362) or a sulphonylurea agent (n = 3070) in 290 UK primary care practices were retrieved from the General Practice Research Database (GPRD). Patients included had an HbA(1c) recorded 0-90 days before and 90-365 days after initiating monotherapy. The probability of achieving glycaemic thresholds in the first year, and for those achieving such targets, the probability of inadequate glycaemic control (HbA(1c) > 6.5%, > 7.0%, > 7.5%) over time is described. RESULTS: Low baseline HbA(1c) and drug initiation within 3 months of diabetes diagnosis were the strongest predictors of initial achievement of glycaemic targets. The proportion of patients with diabetes duration > or = 4 months who achieved HbA(1c) < 7% in the first year ranged from 24% to 88% for highest to lowest baseline HbA(1c) category in sulphonylurea initiators and from 19% to 86% in metformin initiators, with slightly higher proportions for newly diagnosed patients. Kaplan-Meier analyses suggested that 55% and 70% of patients who initially achieved glycaemic targets had HbA(1c) measurements above these targets at 2 and 3 years. CONCLUSIONS: Many patients fail to achieve glycaemic goals with initial monotherapy and, of those who achieve current goals, few consistently maintain these targets over 3 years. Research is needed to evaluate whether more aggressive treatment or alternative treatments can improve the long term maintenance of glycaemic control in patients with Type 2 diabetes. PMID- 17335467 TI - Effect of moderate aerobic exercise on sympatho-vagal balance in Type 2 diabetic patients. AB - AIMS: The purpose of the study was to determine long-term cardiovascular autonomic adaptation to moderate endurance aerobic exercise in people with Type 2 diabetes in order to test the hypothesis of an enhanced vagal drive. METHODS: We analysed the power spectral density of heart rate cyclic variations at rest, while lying, and while standing in 12 sedentary, non-smoking, Type 2 diabetic individuals. Testing was performed before and after a 6-month, supervised, progressive, aerobic training programme, twice weekly. Heart rate variability was assessed by autoregressive power spectral analysis (PSA); this method allows reliable quantification of low-frequency (LF) and high-frequency (HF) components, which are considered to be under mainly sympathetic and purely parasympathetic control, respectively. RESULTS: In 10-min electrocardiogram recordings, mean RR intervals values lying and standing were similar before and after physical exercise. Likewise, total heart rate variability, expressed as total power spectral density (PSD), was not altered by exercise. In contrast, on standing, the HF component, expressed in normalized units, was significantly higher (20.1 +/- 4 vs. 30.4 +/- 5, P < 0.01), whereas the LF component was significantly lower (68.1 +/- 7 vs. 49.8 +/- 8, P < 0.01) after exercise; hence, on standing, the LF/HF ratio, reflecting the sympathetic vs. parasympathetic balance, was markedly lower (16.2 +/- 11 vs. 5.2 +/- 3.2, P = 0.003). No significant exercise-related changes in these PSA components were observed on lying. CONCLUSIONS: A twice weekly, 6-month, moderate, aerobic exercise programme, without a concomitant weight loss diet, is associated with significant improvements in cardiovascular autonomic function in overweight, non-smoking, Type 2 diabetic individuals. PMID- 17335468 TI - Assessing the prevalence, monitoring and management of chronic kidney disease in patients with diabetes compared with those without diabetes in general practice. AB - AIMS: To compare rates of chronic kidney disease (CKD) in patients with diabetes and management of risk factors compared with people without diabetes using general practice computer records, and to assess the utility of serum creatinine and albuminuria as markers of impaired renal function. METHODS: The simplified Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (eGFR) and stage of CKD. Further data were extracted to assess how effectively impaired renal function was being identified and how well potentially modifiable risk factors were being managed. The setting was 17 practices in Surrey, Kent and Greater Manchester (2003-2004). Participants were all patients with serum creatinine (SCr) recorded. RESULTS: Of the total population of 162 113, 5072 were recorded as having a diagnosis of diabetes, giving a prevalence of 3.1%. Of patients with diabetes, 31% had clinically significant CKD (defined as eGFR < 60 ml/min per 1.73 m(2); CKD stages 3-5) compared with 6.9% of those without diabetes. Only 33% of patients with diabetes at CKD stage 3 had serum creatinine > 120 micromol/l. Of patients with diabetes with eGFR < 60 ml/min per 1.73 m(2), 63% had normoalbuminuria. Considering those with eGFR 30-60 ml/min per 1.73 m(2), 42% of people with diabetes were on an ACE inhibitor compared with 25% of those without diabetes; 32% of patients with diabetes who had any record of micro- or macroalbuminuria at CKD stage 3 were taking an ACE inhibitor. Of people with diabetes and hypertension (BP > 140/80 mmHg), 26% were not prescribed any hypertensive medication, regardless of level of CKD. CONCLUSIONS: CKD is common in people with diabetes living in the community in the UK. The study found a similar rate of stage 3-5 CKD to that found previously in the USA. Currently used measures of renal function fail to identify CKD as effectively as eGFR. Risk factors for CKD and its progression are suboptimally managed. PMID- 17335469 TI - Lack of association between serum adiponectin levels and the Pro12Ala polymorphism in Asian Indians. AB - AIMS: The aim of the study was to investigate the association of serum adiponectin levels with the Pro12Ala polymorphism of the peroxisome proliferator activated receptor-gamma (PPARG) gene in Asian Indians. METHODS: We selected 400 diabetic subjects, 200 with the Pro12Pro genotype (100 male and 100 female) and 200 with the Pro12Ala genotype (100 male and 100 female) and 400 age- and sex matched normal glucose tolerance subjects with similar genotype profiles from the Chennai Urban Rural Epidemiology Study. Fasting serum adiponection levels were measured using radioimmunoassay. The Pro12Ala polymorphism was genotyped by PCR restriction fragment length polymorphism using BstUI. RESULTS: All clinical and biochemical parameters were similar in the subjects with the Pro12Pro and Pro12Ala genotypes. There was no significant difference in serum adiponectin values between subjects with the Pro12Pro and Pro12Ala genotypes (males 5.4 vs. 5.8 microg/ml, P = 0.546; females 6.9 vs. 7.2 microg/ml, P = 0.748). Adiponectin values did not differ among these two genotypes even when categorized based on their diabetes status (normal glucose tolerance Pro12Pro 7.9 vs. Pro12Ala 7.7 microg/ml, P = 0.994; diabetes Pro12Pro 4.7 vs. Pro12Ala 5.4 microg/ml, P = 0.622). CONCLUSION: The Pro12Ala polymorphism of the PPARG gene is not associated with serum adiponectin levels in Asian Indians. PMID- 17335470 TI - Studies of associations between the Arg389Gly polymorphism of the beta1 adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects. AB - AIMS: Activation of the beta(1)-adrenergic receptor (ADRB1) causes increased lipolysis in adipose tissue and enhances cardiac output. Analysis of the association of the functional ADRB1 Arg389Gly variant with obesity and hypertension has given ambiguous results. To clarify the potential impact of this variant on obesity and hypertension in the general population, we examined the Arg389Gly variant in a relatively large-scale population-based study. METHODS: Case-control studies and quantitative trait analyses were carried out in 7677 Danish Caucasians who were genotyped for the Arg389Gly variant (dbSNP rs1801253) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: A weak association between the Gly allele of the Arg389Gly variant and obesity was observed when comparing cases (n = 1540) defined as body mass index (BMI) > 30 kg/m(2) with control subjects (n = 6108) defined as BMI < or = 30 kg/m(2) for both allele frequencies (P = 0.05) and genotype distribution (P = 0.05). Case-control studies (cases n = 2518; control n = 3981) examining the effect on hypertension showed no association with allele frequencies (P = 0.3) or genotype distribution (P = 0.5); however, in the quantitative trait analyses, individuals carrying the Gly allele had slightly but significantly lower diastolic (Arg/Arg = 81.9 mmHg vs. Gly-allele carriers = 81.5 mmHg) and systolic (Arg/Arg = 129.4 mmHg vs. Gly-allele carriers = 128.8 mmHg) blood pressure as well as a lower mean arterial blood pressure. CONCLUSION: Our results suggest that the Arg389Gly polymorphism does not have any clinically important impact on the pathogenesis of obesity in Danish white subjects. Furthermore, despite the observed minor influence on blood pressure, this variant is most likely not to be a major contributor to the development of hypertension. PMID- 17335471 TI - Toward a better understanding of contamination of ground water by pesticides. PMID- 17335472 TI - Time to change the way we collect and analyze data for aquifer characterization. PMID- 17335477 TI - On the use and error of approximation in the Domenico (1987) solution. AB - A mathematical solution for solute transport in a three-dimensional porous medium with a patch source under steady-state, uniform ground water flow conditions was developed by Domenico (1987). The solution derivation strategy used an approximate approach to solve the boundary value problem, resulting in a nonexact solution. Variations of the Domenico (1987) solution are incorporated into the software programs BIOSCREEN and BIOCHLOR, which are frequently used to evaluate subsurface contaminant transport problems. This article mathematically elucidates the error in the approximation and presents simulations that compare different versions of the Domenico (1987) solution to an exact analytical solution to demonstrate the potential error inherent in the approximate expressions. Results suggest that the accuracy of the approximate solutions is highly variable and dependent on the selection of input parameters. For solute transport in a medium grained sand aquifer, the Domenico (1987) solution underpredicts solute concentrations along the centerline of the plume by as much as 80% depending on the case of interest. Increasing the dispersivity, time, or dimensionality of the system leads to increased error. Because more accurate exact analytical solutions exist, we suggest that the Domenico (1987) solution, and its predecessor and successor approximate solutions, need not be employed as the basis for screening tools at contaminated sites. PMID- 17335478 TI - Domenico solution--is it valid? AB - The Domenico solution is widely used in several analytical models for simulating ground water contaminant transport scenarios. Unfortunately, many textbook as well as journal article treatments of this approximate solution are full of empirical statements that are developed without mathematical rigor. For this reason, a rigorous analysis of this solution is warranted. In this article, we present a mathematical method to derive the Domenico solution and explore its limits. Our analysis shows that the Domenico solution is a true analytical solution when the value of longitudinal dispersivity is zero. For nonzero longitudinal dispersivity values, the Domenico solution will introduce a finite amount of error. We use an example problem to quantify the nature of this error and suggest some general guidelines for the appropriate use of this solution. PMID- 17335479 TI - Time scales of DNAPL migration in sandy aquifers examined via numerical simulation. AB - The time required for dense nonaqueous phase liquid (DNAPL) to cease migrating following release to the subsurface is a valuable component of a site conceptual model. This study uses numerical simulation to investigate the migration of six different DNAPLs in sandy aquifers. The most influential parameters governing migration cessation time are the density and viscosity of the DNAPL and the mean hydraulic conductivity of the aquifer. Releases of between 1 and 40 drums of chlorinated solvent DNAPLs, characterized by relatively high density and low viscosity, require on the order of months to a few years to cease migrating in a heterogeneous medium sand aquifer having an average hydraulic conductivity of 7.4 x 10(-3) cm/s. In contrast to this, the release of 20 drums of coal tar (rho(D)= 1061 kg/m(3), micro(D)= 0.161 Pa.s) requires more than 100 years to cease migrating in the same aquifer. Altering the mean hydraulic conductivity of the aquifer results in a proportional change in cessation times. Parameters that exhibit relatively little influence on migration time scales are the DNAPL-water interfacial tension, release volume, source capillary pressure, mean aquifer porosity, and ambient ground water hydraulic gradient. This study also demonstrates that low-density DNAPLs (e.g., coal tar) give rise to greater amounts of lateral spreading and greater amounts of pooling on capillary barriers than high-density DNAPLs such as trichloroethylene or tetrachloroethylene. PMID- 17335480 TI - Comparative study of methods for WHPA delineation. AB - Human activities, whether agricultural, industrial, commercial, or domestic, can contribute to ground water quality deterioration. In order to protect the ground water exploited by a production well, it is essential to develop a good knowledge of the flow system and to adequately delineate the area surrounding the well within which potential contamination sources should be managed. Many methods have been developed to delineate such a wellhead protection area (WHPA). The integration of more information on the geologic and hydrogeologic characteristics of the study area increases the precision of any given WHPA delineation method. From a practical point of view, the WHPA delineation methods allowing the simplest and least expensive integration of the available information should be favored. This paper presents a comparative study in which nine different WHPA delineation methods were applied to a well and a spring in an unconfined granular aquifer and to a well in a confined highly fractured rock aquifer. These methods range from simple approaches to complex computer models. Hydrogeological mapping and numerical modeling with MODFLOW-MODPATH were used as reference methods to respectively compare the delineation of the zone of contribution and the zone of travel obtained from the various WHPA methods. Although applied to simple ground water flow systems, these methods provided a relatively wide range of results. To allow a realistic delineation of the WHPA in aquifers of variable geometry, a WHPA delineation method should ensure a water balance and include observed or calculated regional flow characteristics. PMID- 17335481 TI - Seepage face height, water table position, and well efficiency at steady state. AB - When a fully penetrating well pumps an ideal unconfined aquifer at steady state, the water table usually does not join the water level in the well. There is a seepage face inside the well, which is a key element in evaluating the well performance. This problem is analyzed using the finite-element method, solving the complete equations for saturated and unsaturated flow. The seepage face position is found to be almost independent of the unsaturated zone properties. The numerical results are used to test the validity of several analytic approximations. Equations are proposed to predict the seepage face position at the pumping well for any well drawdown, and the water table position at any distance from the pumping well for any in-well drawdown. Practical hints are provided for installing monitoring wells and evaluating well efficiency. PMID- 17335482 TI - Pumping-induced drawdown and stream depletion in a leaky aquifer system. AB - The impact of ground water pumping on nearby streams is often estimated using analytic models of the interconnected stream-aquifer system. A common assumption of these models is that the pumped aquifer is underlain by an impermeable formation. A new semianalytic solution for drawdown and stream depletion has been developed that does not require this assumption. This solution shows that pumping induced flow (leakage) through an underlying aquitard can be an important recharge mechanism in many stream-aquifer systems. The relative importance of this source of recharge increases with the distance between the pumping well and the stream. The distance at which leakage becomes the primary component of the pumping-induced recharge depends on the specific properties of the aquifer, aquitard, and streambed. Even when the aquitard is orders of magnitude less transmissive than the aquifer, leakage can be an important recharge mechanism because of the large surface area over which it occurs. Failure to consider aquitard leakage can lead to large overestimations of both the drawdown produced by pumping and the contribution of stream depletion to the pumping-induced recharge. The ramifications for water resources management and water rights adjudication can be significant. A hypothetical example helps illustrate these points and demonstrates that more attention should be given to estimating the properties of aquitards underlying stream-aquifer systems. The solution presented here should serve as a relatively simple but versatile tool for practical assessments of pumping-induced stream-aquifer interactions. However, this solution should not be used for such assessments without site-specific data that indicate pumping has induced leakage through the aquitard. PMID- 17335483 TI - Heat, chloride, and specific conductance as ground water tracers near streams. AB - Commonly measured water quality parameters were compared to heat as tracers of stream water exchange with ground water. Temperature, specific conductance, and chloride were sampled at various frequencies in the stream and adjacent wells over a 2-year period. Strong seasonal variations in stream water were observed for temperature and specific conductance. In observation wells where the temperature response correlated to stream water, chloride and specific conductance values were similar to stream water values as well, indicating significant stream water exchange with ground water. At sites where ground water temperature fluctuations were negligible, chloride and/or specific conductance values did not correlate to stream water values, indicating that ground water was not significantly influenced by exchange with stream water. Best-fit simulation modeling was performed at two sites to derive temperature-based estimates of hydraulic conductivities of the alluvial sediments between the stream and wells. These estimates were used in solute transport simulations for a comparison of measured and simulated values for chloride and specific conductance. Simulation results showed that hydraulic conductivities vary seasonally and annually. This variability was a result of seasonal changes in temperature-dependent hydraulic conductivity and scouring or clogging of the streambed. Specific conductance fits were good, while chloride data were difficult to fit due to the infrequent (quarterly) stream water chloride measurements during the study period. Combined analyses of temperature, chloride, and specific conductance led to improved quantification of the spatial and temporal variability of stream water exchange with shallow ground water in an alluvial system. PMID- 17335484 TI - A regression model to estimate regional ground water recharge. AB - A regional regression model was developed to estimate the spatial distribution of ground water recharge in subhumid regions. The regional regression recharge (RRR) model was based on a regression of basin-wide estimates of recharge from surface water drainage basins, precipitation, growing degree days (GDD), and average basin specific yield (SY). Decadal average recharge, precipitation, and GDD were used in the RRR model. The RRR estimates were derived from analysis of stream base flow using a computer program that was based on the Rorabaugh method. As expected, there was a strong correlation between recharge and precipitation. The model was applied to statewide data in Minnesota. Where precipitation was least in the western and northwestern parts of the state (50 to 65 cm/year), recharge computed by the RRR model also was lowest (0 to 5 cm/year). A strong correlation also exists between recharge and SY. SY was least in areas where glacial lake clay occurs, primarily in the northwest part of the state; recharge estimates in these areas were in the 0- to 5-cm/year range. In sand-plain areas where SY is greatest, recharge estimates were in the 15- to 29-cm/year range on the basis of the RRR model. Recharge estimates that were based on the RRR model compared favorably with estimates made on the basis of other methods. The RRR model can be applied in other subhumid regions where region wide data sets of precipitation, streamflow, GDD, and soils data are available. PMID- 17335485 TI - Effects of sea-level rise on ground water flow in a coastal aquifer system. AB - The effects of sea-level rise on the depth to the fresh water/salt water interface were simulated by using a density-dependent, three-dimensional numerical ground water flow model for a simplified hypothetical fresh water lens that is similar to shallow, coastal aquifers found along the Atlantic coast of the United States. Simulations of sea-level rise of 2.65 mm/year from 1929 to 2050 resulted in an increase in water levels relative to a fixed datum, yet a net decrease in water levels relative to the increased sea-level position. The net decrease in water levels was much greater near a gaining stream than farther from the stream. The difference in the change in water levels is attributed to the dampening effect of the stream on water level changes in response to sea-level rise. In response to the decreased water level altitudes relative to local sea level, the depth to the fresh water/salt water interface decreased. This reduction in the thickness of the fresh water lens varied throughout the aquifer and was greatly affected by proximity to a ground water fed stream and whether the stream was tidally influenced. Away from the stream, the thickness of the fresh water lens decreased by about 2% from 1929 to 2050, whereas the fresh water lens thickness decreased by about 22% to 31% for the same period near the stream, depending on whether the stream was tidally influenced. The difference in the change in the fresh water/salt water interface position is controlled by the difference in the net decline in water levels relative to local sea level. PMID- 17335486 TI - Ground water sustenance of Nebraska's unique Sand Hills peatland fen ecosystems. AB - Many ecosystems have evolved under conditions where ground water is critical to the survival of the unique species contained therein. One example is Nebraska's Sand Hills fens. The Sand Hills region comprises lush interdunal valleys amid grass-stabilized dunes. One valley type, fens, are ground water-fed wetlands that have several meters of saturated, organic soils comprising peat formed under anaerobic conditions where plant growth exceeds decomposition. These fens support unique flora and fauna such as rush aster and northern redbelly dace that are typically found in more boreal regions of North America. This study characterized the hydrogeology of a representative fen in the Jumbo Valley to explore how these relict species survive in a hot, arid climate and to understand present and historical relations between ground water and these unique ecosystems. Results indicate that ground water's present role in sustaining the fens is twofold: (1) wetland plant transpiration of shallow ground water across the valley creates a cooler, humid microclimate that sustains the fens in the region's hot, arid climate and (2) the large volume of ground water pumped through the fens by plant transpiration transports necessary nutrients to the root zone. Results suggest that, in the past, in addition to its sustaining role, ground water also played a vital role in fen development and in fen preservation through nearly 15,000 years of existence. Thus, as with like ecosystems, the role of ground water must be considered in future Sand Hills fen protection, restoration, and management. PMID- 17335487 TI - Dilution tests in a low-permeability fractured aquifer: matrix diffusion effect. AB - A point dilution test is commonly used in single-borehole tracer experiments designed to determine the Darcy velocity of a formation. This method is based on the concept that, in a borehole, a tracer's concentration declines as a consequence of the water flux. Based on theoretical simulations and field observations, this study indicates that for low-permeability, yet highly porous fractured formations, the common practice of excluding the effect of diffusive mass flux between the dissolved tracer within the borehole and the surrounding matrix may lead to significant errors in the assessment of the Darcy velocity. This conclusion was confirmed by a model adapted to simulate experimental data collected from a tracer test performed in a vertical, large-diameter (25-cm) borehole drilled along a subvertical fracture intersecting a chalk formation. PMID- 17335488 TI - BIOSCREEN-AT: BIOSCREEN with an exact analytical solution. AB - BIOSCREEN is used extensively for screening-level evaluation of the transport of dissolved contaminants in ground water. The code has an effective graphical user interface that makes it ideal for use in both professional practice and as a teaching aid. BIOSCREEN implements the approximate transport solution of Domenico (1987). This note describes an enhanced version of the program, BIOSCREEN-AT, which supplements the Domenico solution with an exact analytical solution. The exact analytical solution has been integrated seamlessly within the BIOSCREEN interface and provides a simple and direct way to calculate an exact solution to the transport equation and, if desired, to assess the significance of the errors introduced by the Domenico (1987) solution for site-specific applications. The modified version of BIOSCREEN is designated BIOSCREEN-AT and can be downloaded free of charge from http://www.sspa.com/./software/BIOSCREEN.htm. PMID- 17335489 TI - The future of hydrogeology, then and now: a look back at O.E. Meinzer's perspectives, 1934 to 1947. PMID- 17335490 TI - New phytologist and the environment. PMID- 17335491 TI - The fine-tuning of heavy metals in mycorrhizal fungi. PMID- 17335492 TI - Linking ozone uptake and defense towards a mechanistic risk assessment for forest trees. PMID- 17335493 TI - Evolving ideas of legume evolution and diversity: a taxonomic perspective on the occurrence of nodulation. AB - Legumes evolved about 60 million years ago (Ma), and nodulation 58 Ma. Nonnodulation remains common in Caesalpinioideae, with smaller numbers in Mimosoideae and Papilionoideae. The first type of infection by bacteria may have been at junctions where lateral roots emerged, followed by formation of infection threads to confine bacteria and convey them to some cells in the developing nodule, where they were generally released into symbiosomes. Infection threads were a prerequisite for root-hair infection, a process better controlled by the host, leading to a higher degree of specificity between symbionts. An alternative process, dating from the same time and persisting in about 25% of legumes, did not involve infection threads, bacteria entering a few host cells, surrounded by an undefined matrix. These cells divided repeatedly to give uniform infected tissue, with bacteria released into symbiosomes. Such legumes may have less stringent control of nodulation processes, and are found mainly in tropical and warm temperate areas. In each type of nodule, meristems may or may not be retained, leading to indeterminate or determinate forms. Nodule morphology and structure are host-determined, but the effectiveness of nitrogen fixation is largely controlled by the bacterial symbionts, which vary greatly in genotypic and phenotypic characters. PMID- 17335494 TI - Pollen limitation meets resource allocation: towards a comprehensive methodology. AB - The standard method of measuring pollen limitation is to add pollen to a number of flowers, preferably to a whole plant, and to compare fruit and seed set with that of naturally pollinated flowers on other plants. In 25 yr of research, this method has yielded valuable data, but it is difficult to use in large plants. This has caused a bias in the available data towards smaller, herbaceous plants with relatively few flowers. I argue that, in order to widen our knowledge of how pollen limitation affects plants, we should go beyond whole-plant pollen addition and change our concept of how a flowering plant functions. The traditional method does not take into account the variation in and dynamics of resource allocation and pollen availability. The concept of integrated physiological units (IPUs) does, but, although it has been applied to pollination biology, it has not received the attention it deserves. I use this article to present its merits again, to propose a step-by-step methodology for studying pollen limitation, and to examine factors influencing possible plant strategies. PMID- 17335495 TI - The use of the zinc-fluorophore, Zinpyr-1, in the study of zinc homeostasis in Arabidopsis roots. AB - * The usefulness of the zinc (Zn)-fluorophore, Zinpyr-1, to examine the localization of Zn in the roots of Arabidopsis has been investigated. * In wild type roots Zinpyr-1 fluorescence was predominantly in the xylem. The fluorescence signal was abolished by the application of the Zn-chelator, N,N,N',N-tetrakis(2 pyridylmethyl)ethylenediamine (TPEN), and was increased by increasing exogenous Zn in the medium, indicating that fluorescence reflected relative Zn concentrations. * In the hma2, hma4 double mutant, which is deficient in root to shoot Zn translocation, Zinpyr-1 fluorescence was low in the xylem and high in the adjacent pericycle cells in which HMA2 and HMA4 are specifically expressed in a wild type. Zinpyr-1 fluorescence was also increased in the endodermis. * These results show that Zinpyr-1 can be used to examine the effects of mutations in Zn transporters on the localization of Zn in Arabidopsis roots and should be a useful addition to the tools available for studying Zn homeostasis in plants. PMID- 17335496 TI - Noncovalent protein transduction in plant cells by macropinocytosis. AB - * Protein delivery across cellular membranes or compartments is primarily limited by low biomembrane permeability. * Many protein transduction domains (PTDs) have previously been generated, and covalently cross-linked with cargoes for cellular internalization. * An arginine-rich intracellular delivery (AID) peptide could rapidly deliver fluorescent proteins or beta-galactosidase enzyme into plant and animal cells in a noncovalent fashion. The possible mechanism of this noncovalent protein transduction (NPT) may involve macropinocytosis. * The NPT via a nontoxic AID peptide provides a powerful tool characterized by its simplicity and quickness to have active proteins function in living cells in vivo. This should be of broad utility for functional enzyme assays and protein therapies in both plant biology research as well as biomedical applications. PMID- 17335497 TI - Actin organization and root hair development are disrupted by ethanol-induced overexpression of Arabidopsis actin interacting protein 1 (AIP1). AB - * Actin organization and dynamics are essential for cell division, growth and cytoplasmic streaming. Here we analyse the effects of the overexpression of Actin Interacting Protein 1 (AIP1) on Arabidopsis development. * Arabidopsis plants were transformed with an ethanol-inducible AIP1 construct and the characteristics of these plants were analysed after induction. * When AIP1 was increased to approx. 90% above wild-type values, root hair development and actin organization in all cell types examined were disrupted. * Our data demonstrate that AIP1 is a key regulator of actin organization and that its regulation is essential for normal plant cell morphogenesis. PMID- 17335498 TI - In vivo visualization of F-actin structures during the development of the moss Physcomitrella patens. AB - * The 'in planta' visualization of F-actin in all cells and in all developmental stages of a plant is a challenging problem. By using the soybean heat inducible Gmhsp17.3B promoter instead of a constitutive promoter, we have been able to label all cells in various developmental stages of the moss Physcomitrella patens, through a precise temperature tuning of the expression of green fluorescent protein (GFP)-talin. * A short moderate heat treatment was sufficient to induce proper labeling of the actin cytoskeleton and to allow the visualization of time-dependent organization of F-actin structures without impairment of cell viability. * In growing moss cells, dense converging arrays of F-actin structures were present at the growing tips of protonema cell, and at the localization of branching. Protonema and leaf cells contained a network of thick actin cables; during de-differentiation of leaf cells into new protonema filaments, the thick bundled actin network disappeared, and a new highly polarized F-actin network formed. * The controlled expression of GFP-talin through an inducible promoter improves significantly the 'in planta' imaging of actin. PMID- 17335499 TI - Chloroplast-located flavonoids can scavenge singlet oxygen. AB - * The hypothesis was tested that flavonoids may scavenge singlet oxygen ((1)O(2)) in mesophyll cells of Phillyrea latifolia exposed to excess-light stress. * In cross-sections taken from leaves developed at 10% (shade) or 100% (sun) solar irradiance, we evaluated the excess photosynthetically active radiation (PAR) induced accumulation of (1)O(2) in mesophyll cells by imaging the fluorescence quenching of the specific (1)O(2) probe N-[2-(diethylamino)ethyl]-N-[(2,5-dihydro 2,2,5,5-tetramethyl-1H-pyrrol-3-yl)methyl]-5-(dimethylamino)-1 naphthalenesulfonamide (DanePy). The intracellular location of flavonoids was also analyzed using three-dimensional deconvolution microscopy. * Photo-induced quenching of DanePy fluorescence was markedly greater in the mesophyll of shade leaves than in that of sun leaves, the former showing a negligible accumulation of mesophyll flavonoids. The photo-induced generation of (1)O(2) was inversely related to the content of flavonoids in the mesophyll cells of sun leaves. Flavonoids were located in the chloroplasts, and were likely associated with the chloroplast envelope. * Here we provide relevant evidence for the potential scavenger activity of chloroplast-located flavonoids against (1)O(2) and new insights into the photo-protective role of flavonoids in higher plants. PMID- 17335500 TI - Insights into the fine architecture of the active site of chicory fructan 1 exohydrolase: 1-kestose as substrate vs sucrose as inhibitor. AB - * Invertases and fructan exohydrolases (FEHs) fulfil important physiological functions in plants. Sucrose is the typical substrate for invertases and bacterial levansucrases but not for plant FEHs, which are usually inhibited by sucrose. * Here we report on complexes between chicory (Cichorium intybus) 1-FEH IIa with the substrate 1-kestose and the inhibitors sucrose, fructose and 2,5 dideoxy-2,5-imino-D-mannitol. Comparisons with other family GH32 and 68 enzyme substrate complexes revealed that sucrose can bind as a substrate (invertase/levansucrase) or as an inhibitor (1-FEH IIa). * Sucrose acts as inhibitor because the O2 of the glucose moiety forms an H-linkage with the acid base catalyst E201, inhibiting catalysis. By contrast, the homologous O3 of the internal fructose in the substrate 1-kestose forms an intramolecular H-linkage and does not interfere with the catalytic process. Mutagenesis showed that W82 and S101 are important for binding sucrose as inhibitor. * The physiological implications of the essential differences in the active sites of FEHs and invertases/levansucrases are discussed. Sucrose-inhibited FEHs show a K(i) (inhibition constant) well below physiological sucrose concentrations and could be rapidly activated under carbon deprivation. PMID- 17335501 TI - Probing the effects of light and temperature on diurnal rhythms of phytosiderophore release in wheat. AB - * The existing literature is ambiguous as to whether the diurnal pulse in phytosiderophore (PS) release in the Poaceae is mediated by light or temperature, or both. * Here, wheat (Triticum aestivum cv. Yecora Rojo) seedlings were grown in Fe-sufficient (pFe = 16.5) and Fe-deficient (pFe = 17.8) chelator-buffered nutrient solutions. Six different light/temperature regimes were tested over 8 d in paired growth chambers. * Phytosiderophore release patterns under a square wave light regime were similar, irrespective of whether temperature was varied diurnally or held constant, but PS release was negligible when the light was removed. Release patterns of PS for Fe-deficient and Fe-sufficient plants grown under the square-wave vs ramped light and temperature regimes were similar in the corresponding Fe treatments. * Our results strongly support the notion that the diurnal pulse in PS release in the Poaceae is mainly mediated by changes in light rather than temperature. Our comparison of square-wave with more natural ramped light/temperature regimes suggests that the diurnal response patterns of PS release in wheat can be confidently studied using traditional square-wave regimes, and this is likely to be the case with other Poaceae as well. PMID- 17335502 TI - Interactive effects of ozone and climate on tree growth and water use in a southern Appalachian forest in the USA. AB - * A lack of data on responses of mature tree growth and water use to ambient ozone (O(3)) concentrations has been a major limitation in efforts to understand and model responses of forests to current and future changes in climate. * Here, hourly to seasonal patterns of stem growth and sap flow velocity were examined in mature trees from a mixed deciduous forest in eastern Tennessee (USA) to evaluate the effects of variations in ambient O(3) exposure and climate on patterns of stem growth and water use. * Ambient O(3) caused a periodic slowdown in seasonal growth patterns that was attributable in part to amplification of diurnal patterns of water loss in tree stems. This response was mediated by statistically significant increases in O(3)-induced daily sap flow and led to seasonal losses in stem growth of 30-50% for most species in a high-O(3) year. * Decreased growth and increased water use of mature forest trees under episodically high ambient O(3) concentrations suggest that O(3) will amplify the adverse effects of increasing temperatures on forest growth and forest hydrology. PMID- 17335503 TI - Interactive effects of ozone and climate on water use, soil moisture content and streamflow in a southern Appalachian forest in the USA. AB - * Documentation of the degree and direction of effects of ozone on transpiration of canopies of mature forest trees is critically needed to model ozone effects on forest water use and growth in a warmer future climate. * Patterns of sap flow in stems and soil moisture in the rooting zones of mature trees, coupled with late season streamflow in three forested watersheds in east Tennessee, USA, were analyzed to determine relative influences of ozone and other climatic variables on canopy physiology and streamflow patterns. * Statistically significant increases in whole-tree canopy conductance, depletion of soil moisture in the rooting zone, and reduced late-season streamflow in forested watersheds were detected in response to increasing ambient ozone levels. * Short-term changes in canopy water use and empirically modeled streamflow patterns over a 23-yr observation period suggest that current ambient ozone exposures may exacerbate the frequency and level of negative effects of drought on forest growth and stream health. PMID- 17335504 TI - The expanded family of ammonium transporters in the perennial poplar plant. AB - * Ammonium and nitrate are the prevalent nitrogen sources for growth and development of higher plants. Here, we report on the characterization of the ammonium transporter (AMT) family in the perennial species Populus trichocarpa. * In silico analysis and expression analysis of AMT genes from poplar was performed. In addition, AMT1;2 and AMT1;6 function was studied in detail by heterologous expression in yeast. * The P. trichocarpa genome contains 14 putative AMTs, which is more than twice the number of AMTs in Arabidopsis. In roots, the high-affinity AMT1;2 strongly increased upon mycorrhiza formation and might be partly responsible for the high-affinity ammonium uptake component measured in poplar. Transcript level for the high-affinity AMT1;6 was strongly affected by the diurnal cycle. AMT3;1 was exclusively expressed in senescing poplar leaves. Remarkably AMT2;1 was highly expressed in leaves while AMT2;2 was mostly expressed in petioles. Specific expression of AMT1;5 in stamen and of AMT1;6 in female flower indicate that they have key functions in reproductive organ development in poplar. * The present study provides basic genomic and transcriptomic information for the poplar AMT family and will pave the way for deciphering the precise role of AMTs in poplar physiology. PMID- 17335505 TI - Metal induction of a Paxillus involutus metallothionein and its heterologous expression in Hebeloma cylindrosporum. AB - * Metallothioneins are small polypeptides involved in metal tolerance of many eukaryotes. Here we characterized the Pimt1 gene, coding for a metallothionein from the ectomycorrhizal fungus Paxillus involutus. * Expression of Pimt1 in P. involutus under metal stress conditions was measured by northern blot and RT-PCR analyses. The full-length cDNA was used to perform functional complementation in yeast mutant strains and agrotransformation of Hebeloma cylindrosporum. * Heterologous expression in yeast showed that PiMT1 was able to complement the hypersensitivity of mutant strains to cadmium (Cd) and copper (Cu), but not to zinc (Zn). Transcripts were almost undetectable under control conditions, whereas Cu and Cd, but not Zn, strongly induced Pimt1 expression in P. involutus. Constitutive overexpression of Pimt1 in H. cylindrosporum conferred a higher copper tolerance. * The present study identified PiMT1 as a potential determinant in the response of mycorrhizal fungi to Cu and Cd stress. Additionally, we demonstrated the usefulness of mycorrhizal fungi transformation using Agrobacterium technology to approach gene function. PMID- 17335506 TI - Early and specific gene expression triggered by rice resistance gene Pi33 in response to infection by ACE1 avirulent blast fungus. AB - * Our view of genes involved in rice disease resistance is far from complete. Here we used a gene-for-gene relationship corresponding to the interaction between atypical avirulence gene ACE1 from Magnaporthe grisea and rice resistance gene Pi33 to better characterize early rice defence responses induced during such interaction. * Rice genes differentially expressed during early stages of Pi33/ACE1 interaction were identified using DNA chip-based differential hybridization and QRT-PCR survey of the expression of known and putative regulators of disease resistance. * One hundred genes were identified as induced or repressed during rice defence response, 80% of which are novel, including resistance gene analogues. Pi33/ACE1 interaction also triggered the up-regulation of classical PR defence genes and a massive down-regulation of chlorophyll a/b binding genes. Most of these differentially expressed genes were induced or repressed earlier in Pi33/ACE1 interaction than in the gene-for-gene interaction involving Nipponbare resistant cultivar. * Besides demonstrating that an ACE1/Pi33 interaction induced classical and specific expression patterns, this work provides a list of new genes likely to be involved in rice disease resistance. PMID- 17335507 TI - The genetic basis of quantitative variation in susceptibility of Arabidopsis thaliana to Pseudomonas syringae (Pst DC3000): evidence for a new genetic factor of large effect. AB - * Pathogens represent an important threat to plant communities and agriculture, and can shape many aspects of plant evolution. Natural variation in plant disease susceptibility is typically quantitative, yet studies on the molecular basis of disease resistance have focused mainly on qualitative variation. * Here we investigated the genetic architecture of quantitative susceptibility to the bacterium Pseudomonas syringae by performing a quantitative trait locus (QTL) analysis on the F2 progeny of two natural accessions of Arabidopsis thaliana under two nutrient treatments. * We found that a single QTL explains most of the variation (77%) in susceptibility between accessions Columbia (Col-0) and San Feliu-2 (Sf-2), and its effect is independent of nutrients. The Sf-2 allele at this QTL is dominant and can reduce the bacterial population size by 31-fold, much like a classical resistance (R) gene. However, minor QTLs, whose effects are altered by nutrient treatment, were also detected. * Surprisingly, we found that none of the QTLs for susceptibility had any effect on fruit production, suggesting that the use of resistance genes for crop improvement and evolutionary analysis of plant-pathogen interactions requires caution. PMID- 17335508 TI - Importance of plasticity and decision-making strategies for plant resource acquisition in spatio-temporally variable environments. AB - * Plants must cope with environmental variation in space and time. Phenotypic plasticity allows them to adjust their form and function to small-scale variations in habitat quality. Empirical studies have shown that stoloniferous plants can exploit heterogeneous habitats through plastic ramet specialization and internal resource exchange (division of labour). * Here we present a spatially explicit simulation model to explore costs and benefits of plasticity in spatio-temporally heterogeneous environments. We investigated the performance of three plant strategies in pairwise competition. The nonplastic strategy was unable to specialize. The autonomous plastic strategy displayed localized responses to external resource signals. In the coordinated plastic strategy, localized responses could be modified by internal demand signals from connected modules. * Plasticity in resource uptake proved beneficial in a broad range of environments. Modular coordination was beneficial under virtually all realistic conditions, especially if resource supplies did not closely match resource needs. * The benefits of division of labour extend considerably beyond the parameter combination covered by empirical studies. Our model provides a general framework for evaluating the benefits, costs and limits of plasticity in spatio-temporally heterogeneous habitats. PMID- 17335509 TI - 'Inconstant males' and the maintenance of labile sex expression in subdioecious plants. AB - * Here, we evaluate the role of pollen limitation and selfing in the maintenance of labile sex expression in subdioecious plant species. * We used a literature survey to explore which factors correlated with a significant occurrence of hermaphrodites in dioecious species. We developed models to explore the selective maintenance of labile sex expression. The models had similar ecological assumptions but differed in the genetic basis of sex lability. * We found that a significant frequency of hermaphrodites was associated with animal pollination, and that hermaphrodites were 'inconstant' males with perfect flowers, suggesting evolution through the gynodioecious pathway. Models showed that a modifier converting pure males into inconstant males could be maintained under a wide range of reduction in both male and female fitness. Pollen limitation and self fertilization facilitated invasion of the modifier. Depending on the genetics of sex determination, we found pure dioecy, stable subdioecy (trioecy), and situations where inconstant males coexisted with either pure females or pure males. Under selfing and pollen limitation, certain conditions selected for inconstant males which will drive populations to extinction. * We discuss our results in relation to the evolution towards, and the breakdown of, dioecy, and the ecological and evolutionary implications of labile sex expression. PMID- 17335510 TI - Monitoring in planta bacterial infection at both cellular and whole-plant levels using the green fluorescent protein variant GFPuv. AB - * Green fluorescent protein (GFP) labeling of bacteria has been used to study their infection of and localization in plants, but strong autofluorescence from leaves and the relatively weak green fluorescence of GFP-labeled bacteria restrict its broader application to investigations of plant-bacterial interactions. * A stable and broad-host-range plasmid vector (pDSK-GFPuv) that strongly expresses GFPuv protein was constructed not only for in vivo monitoring of bacterial infection, localization, activity, and movement at the cellular level under fluorescence microscopy, but also for monitoring bacterial disease development at the whole-plant level under long-wavelength ultraviolet (UV) light. * The presence of pDSK-GFPuv did not have significant impact on the in vitro or in planta growth and virulence of phytobacteria. A good correlation between bacterial cell number and fluorescence intensity was observed, which allowed us to rapidly estimate the bacterial population in plant leaf tissue. We demonstrated that GFPuv-expressing bacteria can be used to screen plants that are compromised for nonhost disease resistance and Agrobacterium attachment. * The use of GFPuv-labeled bacteria has a wide range of applications in host-bacterial interaction studies and bacterial ecology-related research. PMID- 17335511 TI - Screening of the endothelin1 gene (EDN1) in a cohort of patients with essential left ventricular hypertrophy. AB - Our objective was to analyse the role of endothelin1 gene (EDN1) variation in essential left ventricular hypertrophy (LVH). We searched for EDN1 variants in 145 Spanish patients with an essential form of LVH (not secondary to hypertension, aortic stenosis, or any other disease that could explain the hypertrophy). The five EDN1 coding exons and 1.5 kilobases of the promoter region were analysed through single strand conformation analysis and direct sequencing. We found four nucleotide changes: -1224 C/A (promoter), -131 ins/del A (exon 1, 5'-non-translated sequence), A/G in codon 106 (exon 3, silent), and G/T in codon 198 (exon 5, lys198asn). To determine the association between these polymorphisms and cardiac hypertrophy, we compared the genotype frequencies from these 145 patients with 250 healthy controls. We found a higher frequency of patients homozygous for 198 lys (198 KK) (65% vs. 52%; p = 0.01; OR = 1.76) and for -1224 AA (73% vs. 66%; p = 0.19). Homozygotes for -1224 A + 198 K (AA+KK) were significantly more frequent in patients (62% vs. 45%; p = 0.0007; OR = 2.10; 95% CI = 1.35-3.25). The expression of the -1224 C/A and exon 5 K198N variants was analysed with cells in culture. These in vitro studies showed that these variations did not differ in their expression levels. In conclusion, our work has shown that EDN1 variation, and in particular homozygosity for the -1224A/198K haplotype, is associated with the risk of developing cardiac hypertrophy. However, these EDN1 variants do not affect in vitro gene expression. PMID- 17335512 TI - Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis. AB - Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which is derived from NAD, have important roles as a redox carriers in metabolism. A combination of de novo and salvage pathways contribute to the biosynthesis of NAD in all organisms. The pathways and enzymes of the NAD salvage pathway in yeast and animals, which diverge at nicotinamide, have been extensively studied. Yeast cells convert nicotinamide to nicotinic acid, while mammals lack the enzyme nicotinamidase and instead convert nicotinamide to nicotinamide mononucleotide. Here we show that Arabidopsis thaliana gene At2g22570 encodes a nicotinamidase, which is expressed in all tissues, with the highest levels observed in roots and stems. The 244-residue protein, designated AtNIC1, converts nicotinamide to nicotinic acid and has a Km value of 118 +/- 17 microM and a Kcat value of 0.93 +/- 0.13 sec(-1). Plants homozygous for a null AtNIC1 allele, nic1-1, have lower levels of NAD and NADP under normal growth conditions, indicating that AtNIC1 participates in a yeast-type NAD salvage pathway. Mutant plants also exhibit hypersensitivity to treatments of abscisic acid and NaCl, which is correlated with their inability to increase the cellular levels of NAD(H) under these growth conditions, as occurs in wild-type plants. We also show that the growth of the roots of wild-type but not nic1-1 mutant plants is inhibited and distorted by nicotinamide. PMID- 17335513 TI - Structural and functional characterization of ferredoxin-NADP+-oxidoreductase using knock-out mutants of Arabidopsis. AB - In Arabidopsis thaliana, the chloroplast-targeted enzyme ferredoxin-NADP+ oxidoreductase (FNR) exists as two isoforms, AtLFNR1 and AtLFNR2, encoded by the genes At5g66190 and At1g20020, respectively. Both isoforms are evenly distributed between the thylakoids and soluble stroma, and they are separated by two dimensional electrophoresis in four distinct spots, suggesting post-translational modification of both isoforms. To reveal the functional specificity of AtLFNR1, we have characterized the T-DNA insertion mutants with an interrupted At5g66190 gene. Absence of AtLFNR1 resulted in a reduced size of the rosette with pale green leaves, which was accompanied by a low content of chlorophyll and light harvesting complex proteins. Also the photosystem I/photosystem II (PSI/PSII) ratio was significantly lower in the mutant, but the PSII activity, measured as the F(V)/F(M) ratio, remained nearly unchanged and the excitation pressure of PSII was lower in the mutants than in the wild type. A slow re-reduction rate of P700 measured in the mutant plants suggested that AtLFNR1 is involved in PSI dependent cyclic electron flow. Impaired function of FNR also resulted in decreased capacity for carbon fixation, whereas nitrogen metabolism was upregulated. In the absence of AtLFNR1, we found AtLFNR2 exclusively in the stroma, suggesting that AtLFNR1 is required for membrane attachment of FNR. Structural modeling supports the formation of a AtLFNR1-AtLFNR2 heterodimer that would mediate the membrane attachment of AtLFNR2. Dimer formation, in turn, might regulate the distribution of electrons between the cyclic and linear electron transfer pathways according to environmental cues. PMID- 17335514 TI - Identification of an arsenic tolerant double mutant with a thiol-mediated component and increased arsenic tolerance in phyA mutants. AB - A genetic screen was performed to isolate mutants showing increased arsenic tolerance using an Arabidopsis thaliana population of activation tagged lines. The most arsenic-resistant mutant shows increased arsenate and arsenite tolerance. Genetic analyses of the mutant indicate that the mutant contains two loci that contribute to arsenic tolerance, designated ars4 and ars5. The ars4ars5 double mutant contains a single T-DNA insertion, ars4, which co-segregates with arsenic tolerance and is inserted in the Phytochrome A (PHYA) gene, strongly reducing the expression of PHYA. When grown under far-red light conditions ars4ars5 shows the same elongated hypocotyl phenotype as the previously described strong phyA-211 allele. Three independent phyA alleles, ars4, phyA-211 and a new T-DNA insertion allele (phyA-t) show increased tolerance to arsenate, although to a lesser degree than the ars4ars5 double mutant. Analyses of the ars5 single mutant show that ars5 exhibits stronger arsenic tolerance than ars4, and that ars5 is not linked to ars4. Arsenic tolerance assays with phyB-9 and phot1/phot2 mutants show that these photoreceptor mutants do not exhibit phyA-like arsenic tolerance. Fluorescence HPLC analyses show that elevated levels of phytochelatins were not detected in ars4, ars5 or ars4ars5, however increases in the thiols cysteine, gamma-glutamylcysteine and glutathione were observed. Compared with wild type, the total thiol levels in ars4, ars5 and ars4ars5 mutants were increased up to 80% with combined buthionine sulfoximine and arsenic treatments, suggesting the enhancement of mechanisms that mediate thiol synthesis in the mutants. The presented findings show that PHYA negatively regulates a pathway conferring arsenic tolerance, and that an enhanced thiol synthesis mechanism contributes to the arsenic tolerance of ars4ars5. PMID- 17335515 TI - Unusual macular degeneration following breast cancer. PMID- 17335516 TI - Relationship between night myopia and night-time motor vehicle accidents. AB - PURPOSE: To investigate the relationship between night myopia and the occurrence of night-time motor vehicle accidents in a group of professional drivers. METHODS: We examined 136 professional drivers. Refraction was determined in full illumination (100 cd/m2) and after sitting in darkness for 5 mins. The change in refraction, indicative of night myopia, was correlated with the number of motor vehicle accidents in which each driver was involved (detailed in their personal files) and with the results of a visual complaints questionnaire. RESULTS: The mean age of the study group was 21.0 years. Mean spherical refraction changed from + 0.11 dioptres (D) in light to -0.17 D after dark adaptation for 5 mins. Night myopia was found in 34 drivers (25%), at a mean of -1.2 D (range -0.75 D to -3.50 D). There was no statistically significant difference between these drivers and the rest of the group in the results of the visual complaints questionnaire, or in the number of accidents occurring during the day. However, drivers with a myopic shift > 0.75 D were involved in more accidents at night than the rest of the group (p = 0.044). CONCLUSIONS: In this study population, drivers with night myopia of > 0.75 D were more likely to be involved in night-time accidents. This may imply that selected groups of drivers should be examined for night myopia. PMID- 17335517 TI - A 'gallop' through history: nursing in social context. PMID- 17335518 TI - Hand hygiene among nurses in Turkey: opinions and practices. AB - AIMS AND OBJECTIVES: This study aims to identify nurses' practices and opinions of handwashing during routine patient care. BACKGROUND: Transmission of microorganisms from the hands of healthcare workers is the main source of cross infection in hospitals and can be prevented by handwashing. DESIGN AND METHODS: A questionnaire survey was used for this study. A total of 129 clinical nurses at University of Ege Faculty of Medicine Application and Investigation Hospital at Internal Medicine Clinics was surveyed with a response rate of 100%. Data analysis was carried out using SPSS version 10. RESULTS: The study revealed that nurses have a poor level of knowledge concerning quality of hand washing. All nursing actions related to 'clean' and 'dirty' activities were evaluated using the Fulkerson scale. The majority of nurses reported that they always wash hands after contact with contaminated and non-contaminated patients, equipment and environment. It was found that they did need to wash their hands often but that they were not able to do this because of dense working conditions, insufficiency of necessary materials and drying and sore of hands after frequent washing. CONCLUSION: To improve hand hygiene and quality of handwashing compliance, additional factors must be considered. These factors include improving healthcare workers--especially nurses'--skin conditions, hand hygiene techniques and disinfections substantially. RELEVANCE TO CLINICAL PRACTICE: Hospitals need to develop and implement innovative educational and motivational programmes tailored to specific groups of health personnel. PMID- 17335519 TI - Struggling for confirmation--patients' experiences of dissatisfaction with hospital care. AB - AIM: The aim of the study was to illuminate patients' experiences of dissatisfaction with hospital care. BACKGROUND: During the last decade, interest in measuring patient satisfaction has become an important indicator of the quality of care. Researchers have, however, criticized the concept theoretically and methodologically. Subsequently, researchers have increasingly argued that the focus of attention should shift to explore patient dissatisfaction. DESIGN: A qualitative approach. METHODS: Narrative interviews were conducted with six people who had experienced dissatisfaction during a hospital care episode. The interview text was analysed using qualitative content analysis. RESULTS: The results show the patients' struggle for confirmation, the feeling of distrust in health care and what they have been forced to sacrifice because of lack of treatment. A feeling of being a troublesome patient is also apparent. At the same time a positive encounter is described, as well as situations of confirmation from caregivers. The results also show hope and a will to get on with life. CONCLUSIONS: Dissatisfaction relating to aspects of encounter is a common problem in health care and conceivable causes and possible solutions are discussed from different perspectives. RELEVANCE TO CLINICAL: PRACTICE: Caregivers as well as patients are in need of confirmation. If management were to take notice of and confirm caregivers this could consequently help them to gain the strength and energy necessary to provide care permeated with confirmation. A veritable, trustworthy care can be established through personal presence. To take notice of, confirm and listen to patients, creates opportunities for providing them with a positive experience of human encounter, which in the long run is rewarding from all perspectives. PMID- 17335520 TI - Nurses relate the contributing factors involved in medication errors. AB - AIMS AND OBJECTIVES: Understanding the processes by which nurses administer medication is critical to the minimization of medication errors. This study investigates nurses' views on the factors contributing to medication errors in the hope of facilitating improvements to medication administration processes. DESIGN AND METHODS: A focus group of nine Registered Nurses discussed medication errors with which they were familiar as a result of both their own experiences and of literature review. The group, along with other researchers, then developed a semi-structured questionnaire consisting of three parts: narrative description of the error, the nurse's background and contributing factors. After the contributing factors had been elicited and verified with eight categories and 34 conditions, additional Registered Nurses were invited to participate by recalling one of the most significant medication errors that they had experienced and identifying contributing factors from those listed on the questionnaire. Identities of the hospital, patient and participants involved in the study remain confidential. RESULTS: Of the 72 female nurses who responded, 55 (76.4%) believed more than one factor contributed to medication errors. 'Personal neglect' (86.1%), 'heavy workload' (37.5%) and 'new staff' (37.5%) were the three main factors in the eight categories. 'Need to solve other problems while administering drugs,''advanced drug preparation without rechecking,' and 'new graduate' were the top three of the 34 conditions. Medical wards (36.1%) and intensive care units (33.3%) were the two most error-prone places. The errors common to the two were 'wrong dose' (36.1%) and 'wrong drug' (26.4%). Antibiotics (38.9%) were the most commonly misadministered drugs. CONCLUSIONS: Although the majority of respondents considered nurse's personal neglect as the leading factor in medication errors, analysis indicated that additional factors involving the health care system, patients' conditions and doctors' prescriptions all contributed to administration errors. RELEVANCE TO CLINICAL PRACTICE: Identification of the main factors and conditions contributing to medication errors allows clinical nurses and administration systems to eliminate situations that promote errors and to incorporate changes that minimize them, creating a safer patient environment. PMID- 17335521 TI - Bowel function among people 75+ reporting faecal incontinence in relation to help seeking, dependency and quality of life. AB - AIMS AND OBJECTIVES: The aim was to compare faecal incontinence and related bowel symptoms among men and women and being dependent or not (aged >or=75 years) and furthermore to identify which bowel symptoms predicted help seeking, dependency and low quality of life (QoL). BACKGROUND: Faecal incontinence (FI) in old age is a common condition and influences daily life to a great extent, although few actually seek medical help. METHODS: A total of 248 people with reported difficulties controlling faeces answered a postal questionnaire or were interviewed with questions about FI-related bowel symptoms. A factor analysis resulted in four areas of bowel symptoms and was used in logistic regression with help seeking, dependency and low QoL as dependent variables. RESULTS: Of all the subjects, 56.4% had leakage, 54.7% did not reach the toilet in time, 55.6% had incomplete emptying, 27.9% had hard stool, 36.8% bother from moisture from the anus, 32.2% could not withstand urgency for five minutes and 17% had red skin or wounds in the genital region. Women and those dependent were most affected. Totally 40.8% had sought help and 30.1% used protective aids. Leakage, discomfort, consistency and contractibility symptoms were the categories of bowel symptoms related to FI. Discomfort predicted help seeking (OR 3.0), dependency (OR 1.5) and physical QoL (OR 1.7). Leakage predicted help seeking (OR 1.9) but not dependency and QoL. CONCLUSIONS: Overall bowel function was disturbed among those with FI and unmet needs seem problematic especially for women and those needing help in Activities of Daily Living (ADL). Encouragement to seek and get medical help and to use protective aids may improve the very low quality of life in this group. RELEVANCE TO CLINICAL PRACTICE: Older people with FI should be asked about, assessed for and examined for overall bowel function to get adequate treatment and be encouraged to use protection. PMID- 17335522 TI - The experiences of older people on discharge from hospital following assessment by the public health nurse. AB - AIMS AND OBJECTIVES: The aim of the study was to explore the experiences of older people on discharge from hospital following assessment by the public health nurse. The objectives of the study were to: (i) identify needs as perceived by older people, (ii) examine if older people felt that these needs were met, (iii) examine the support/care/services received by older people, and (iv) explore any unmet needs of older people. BACKGROUND: A review of the literature revealed that discharge from hospital remains an area of concern as older people had varying degrees of met and unmet need following discharge from acute hospital. DESIGN/METHODS: A qualitative study using a phenomenological approach was undertaken. The researcher carried out interviews with a purposive sample of 11 older people in their homes two weeks following discharge from acute hospital. Data were analysed using Colaizzi's method. RESULTS: Older people experienced a wide variety of difficulties in managing aspects of their own care. A reassuring finding of this study is that older people received assistance in this initial discharge period, i.e. they experienced significant informal support complemented by statutory and voluntary support. Even though these older people were assessed by the public health nurse, their need to access services, for statutory service provision, social aspects of their lives and safety measures in their environment were not met. Older people expressed the wish to remain in their own homes. CONCLUSION: Assessment of older people by the public health nurse is meaningful to identify the needs of older people and provide for the needs of older people though this does not necessarily mean that all the needs of older people can be met by the public health nurse. This study supports the findings of other studies of the problems after discharge and provides an understanding of the experiences of older people on discharge from hospital following assessment by the public health nurse from their perspective. RELEVANCE TO CLINICAL PRACTICE: The study will provide information that will contribute to current public health nurse practice and will contribute to the understanding of public health nurse practice. PMID- 17335523 TI - A qualitative study explaining nurses' perceptions of quality care for older people in long-term care settings in Ireland. AB - AIM: The aim of this research was to explore nurses' perceptions of the attributes of quality care and the factors that facilitate or hinder high-quality nursing care in long-term care. BACKGROUND: The quality of care for older people living in long-term care has been identified as an issue of concern in many nursing research studies. While many factors have been identified, it is difficult to determine key factors from current research. METHOD: The study was a qualitative exploration of nurses' perceptions of quality care for older people and the factors that facilitate or hinder quality care. It involved 20 interviews with nurses. Respondents were asked to illustrate their accounts with examples from practice. This phase of the research was guided by the principles of hermeneutic phenomenology and the analysis process by Van Manen. FINDINGS: The findings indicated that nurses perceived quality care for older people in Ireland as holistic, individualized and focused on promoting independence and choice. The research revealed, however, that care in many practice areas was not individualized, patient choice and involvement in decision making was limited and some areas engendered dependency. While staffing was identified as a factor which had an impact on the provision of patient choice, other issues, such as the motivation of staff, the role of the ward manager and the dominance of routine were also highlighted. CONCLUSION: There is a need to review organizational approaches to care, develop patient centred approaches to care and provide educational support for managers. RELEVANCE TO PRACTICE: This research focuses on care for older people; it helps practitioners identify key factors in the provision of quality care for older people living in long-term care. PMID- 17335524 TI - Nurses' feelings and thoughts about using physical restraints on hospitalized older patients. AB - AIM: To explore nurses' feelings and thoughts about physically restraining older hospitalized patients. BACKGROUND: The use of physical restraints is still highly prevalent in hospitals; furthermore, older patients are most likely to be so restrained. Studies in acute care settings have focused mainly on nurses' knowledge, attitudes, or practice concerning physical restraints, on physical restraint reduction programmes, on nurses' perceptions about the use of physical restraints, or on elderly patients' experiences with physical restraints. To the best of our knowledge no studies have been conducted on hospital nurses' feelings and thoughts about the use of physical restraints in Taiwan. DESIGN AND METHODS: A qualitative approach was used to understand this phenomenon. Semi-structured interviews were carried out, from August 2002 to March 2003, with 12 nurses working in three hospitals. The interviews were audiotaped and transcribed verbatim; content analysis was used to analyse the data. RESULTS: Nurses reported a variety of emotional responses regarding the use of physical restraints, including sadness, guilt, conflicts, retribution, absence of feelings, security, and pity for the restrained older people. Rationalization, sharing with colleagues, and compensating behaviours were ways that nurses used to manage their negative feelings. CONCLUSIONS: Most nurses had negative feelings towards the use of physical restraints. Among these nurses there was a struggle between patients' autonomy and the practice of care. However, other nurses said they had 'no feelings' or 'feeling of security' while using physical restraints. RELEVANCE TO CLINICAL PRACTICE: The findings of this study may contribute to filling the gaps in nursing knowledge, to improving protocols for physical restraint use in hospitals, and may also assist nurse managers to create a supportive practice environment. It is recommended that in-service training programmes should cover misconceptions regarding physical restraint use, ethical issues and how to cope with feelings while using physical restraints. PMID- 17335525 TI - Falls in German in-patients and residents over 65 years of age. AB - AIMS AND OBJECTIVES: The aim of the present study was to describe the first fall rates in hospitals and nursing homes throughout Germany. Relationships between age, gender, care dependency, medical disciplines, bed confinement and falls were investigated. BACKGROUND: Little is known about fall rates in German hospitals and nursing homes. METHOD: Prevalence studies were conducted in the year 2002 and 2004. Forty hospitals and 15 nursing homes took part in 2002 (3923 patients and 1252 residents older than 65 years) and in 2004 there was a total of 39 hospitals and 29 nursing homes (4451 patients and 2374 residents older than 65 years). Staff nurses used a standardized instrument to collect data about falls in the last two weeks in their institutions and also about other patient problems. Descriptive and inferential statistics were used as well as logistic regression. RESULTS: The first fall rate in 2002 (2004) in the hospitals was 4.7 (4.2) and in the nursing homes 4.5 (5.1) per 1000 patient/resident days. Most of the hospital patients fell on geriatric wards. The high care dependent patients fell more often than the low care dependent patients. In 2002, mobile nursing home residents were at a higher risk of falling than residents confined to bed, but those results could not be confirmed in 2004. Conclusions. Falls of patients over 65 years of age are as much of a problem in German hospitals as they are in German nursing homes. RELEVANCE TO CLINICAL PRACTICE: Fall preventive methods should be implemented both in nursing homes and hospitals. Care dependency is a stable risk factor for falls in hospital patients. PMID- 17335526 TI - Identifying the most efficient items from the Mini-Mental State Examination for cognitive function assessment in older Taiwanese patients. AB - AIMS: The purpose of the study was to identify the most efficient items from the Mini-Mental State Examination for assessment of cognitive function. BACKGROUND: The Mini-Mental State Examination is the most frequently used cognitive screening instrument. However, the Mini-Mental State Examination has been criticized for insensitivity to mild cognitive dysfunction, limited memory assessment and variability in level of difficulty of the individual items. METHOD: This study used secondary data analysis. Item response theory two-parameter model was used to analyse the data from the admission assessment of mental status by the Mini Mental State Examination for 801 patients. RESULTS: By using item response analysis, 16 items were selected from the original 30-item Mini-Mental State Examination. The 16 items included mainly the measures of orientation, recall and attention and calculation. The internal consistency of the 16-item Mini-Mental State Examination was 0.84. The proposed new cut-off point for the 16-item Mini Mental State Examination was 11. The correct classification rate was 0.94, the sensitivity was 100% and the specificity was 97.4%, when compared with the original 30-item Mini-Mental State Examination from the cut-off point of 24. This new cut-off point was determined for the purpose of over-identifying patients at risk so as to ensure early detection of and prevention from the onset of cognitive disturbance. CONCLUSION: Only a few items are needed to describe the subject's cognitive status. Using item response theory analysis, the study found that the Mini-Mental State Examination could be simplified. RELEVANCE TO CLINICAL PRACTICE: Deleting the items with less variation makes this assessment tool not only shorter, easier to administer and less strenuous for respondents, but also enables one to maintain validity as a cognitive function test for clinical setting. PMID- 17335527 TI - Women's conception of the menopausal transition--a qualitative study. AB - AIM: To explore, with a qualitative approach, whether the conception of menopause varies between women seeking medical advice because of climacteric symptoms and, if so, to describe these different conceptions. BACKGROUND: For many women, the menopausal transition is a troublesome period of life, often associated with decreased well-being and a number of symptoms. Besides the hormonal changes, many other factors such as psychological, sociological and lifestyle factors affect how women perceive their menopause. METHOD: Semi-structured interviews were held with 20 women after their first-time visits at outpatient clinics of gynaecology for discussion of climacteric symptoms. The interviews were audio-taped, transcribed and analysed using a phenomenographic approach. RESULTS: A wide variation of conceptions was revealed. Two main categories were identified including different physical changes with varying symptoms and both positive and negative psychological changes. The menopausal transition was also described as a natural process and as a developmental phase of life. CONCLUSION: Women's conceptions of the menopausal transition were individual and contained both physical and psychological symptoms but also expressed a more holistic view of the menopausal transition. The transition was described as a natural process affected by endocrine and life-style factors as well as by the psychosocial situation and by ageing per se. RELEVANCE TO CLINICAL PRACTICE: It is important that health care providers are aware of women's conceptions about the menopausal transition to be able to communicate optimally, support and empower middle-aged women in different health care situations and thereby optimize the result of care. PMID- 17335528 TI - What does partnership in care mean for children's nurses? AB - AIM AND OBJECTIVE: To explore partnership in care with a small sample of children's nurses in an inner city trust. (i) To obtain local data on what a sample of children's nurses understand by partnership in care and to what degree partnership in care is evident in their practice; (ii) where feasible, to compare these data with national and international literatures describing partnership in care and provide pointers that will be useful in contributing and responding to the children's national service framework. BACKGROUND: Partnership in care has been practised within children's nursing in UK for over a decade, but is an amorphous topic. More recently, it has been suggested that partnership in care can be described as a part of the spectrum of family-centred care. An exploratory study with 10 experienced children's nurses was undertaken to determine what they understood by the term partnership in care. RESULTS: Seven categories emerged from the data: attitudes, respect for family, communication, parent understanding, effective partnership, all parties (satisfied) and improved well being. CONCLUSION: It is suggested that a negative approach to one of the first four categories leads to ineffective partnership in care. RELEVANCE TO CLINICAL PRACTICE: Attitudes, respect for the family and communication should improve to enhance the practice of partnership in care. Respect for the child and family and communication have both been identified as important qualities within the new National Service Framework for Children, Young People and Maternity Services. Further research is suggested to determine the applicability of these findings to other members of the multi-disciplinary team. PMID- 17335529 TI - An exploration of best practice in multi-agency working and the experiences of families of children with complex health needs. What works well and what needs to be done to improve practice for the future? AB - AIMS AND OBJECTIVES: This Appreciative Inquiry study aimed to explore appreciatively examples of best multi-agency working practice with families (mothers, n = 20; fathers, n = 7; children, n = 1) and people working with children with complex needs (n = 41), to determine what works well, why it has worked well and what best practice in the future could be. BACKGROUND: The term 'children with complex health needs' encompasses a diverse group of children and this population is increasing. This diverse group of children often requires high levels of physiological, psychological and social care which brings them and their families into therapeutic contact with a wide range of health, social and education professionals and people from other agencies. DESIGN: The study used appreciative interviews, nominal group workshops and consensus workshops to develop a set of 10 'best practice' guidelines that reflected the views of all participants. Two of these are discussed in detail in this article. All participants were seen as co-researchers whose expert contributions were vital to understanding of what works well and what needs to be done in multi-agency working practice. RESULTS: The study resulted in 'best practice' statements that illuminated 'what works well' in multi-agency working practice that spanned issues including information, decision making, communication, accessibility, collaboration, respect and sharing a common vision. CONCLUSIONS: The guidance that results from this study suggests that parents need the opportunity to share and receive support from other parents who understand the lived reality of caring for a child with complex needs. Parents and people from across various agencies need to work together to ensure that the most appropriate person acts in the role of a long-term coordinator, where the family wants this aspect of support. This study adds a multi-disciplinary and appreciatively oriented focus on what works well in complex care. It contributes to an understanding of the value of an Appreciative Inquiry approach within health-care research. RELEVANCE TO CLINICAL PRACTICE: The guidelines arose from and are grounded in practice and as such they provide clear, workable directions for enhancing practice and for considering what already does work well. PMID- 17335530 TI - Children's nurses and nurse prescribing: a case study identifying issues for developing training programmes in the UK. AB - AIMS AND OBJECTIVES: (1) To develop an insight into the opportunities and barriers to nurse prescribing for a case study of children's nurses. (2) To consider the implications of independent nurse prescribing for children's nurses and the potential for nurse prescribing to be developed in acute children's care settings. (3) To use research data to develop a training strategy. BACKGROUND: Nurse prescribing in the UK is evolving and current initiatives aim to extend the range and scope of prescribing. Children's nursing presents interesting challenges because of off-license drugs. Successful nurse prescribing lies in practice area preparation, local policy and practice development and identifying precourse training needs. DESIGN: Case study. RESEARCH QUESTIONS: (1) What opportunities do children's nurses identify as being appropriate for nurse prescribing? (2) Can children's nurses identify the benefits of patient group directives and the different levels of nurse prescribing? (3) What preparation do children's nurses need for nurse prescribing? METHODS: Focus group of health visitors/district nurses to inform a survey of 500 nurses working in acute and specialist care settings in a large Children's Hospital. Results. Focus group main themes - training, supervision and the development of confidence, record keeping, benefits of nurse prescribing, autonomous practice, the formulary and its use in practice. Response rate was 27%. Senior nurses and specialists identified potential benefits for their practice. Course content needed to focus on children, i.e. children's physiology and pharmokinetics. Children's nurses frequently advise junior medical colleagues on prescribing issues. Patient group directives are a useful alternative to prescribing. CONCLUSIONS: The results provide an insight into the training needs of children's nurses and specialist nurses which may be used to develop nurse prescribing training and practice. Training may need to be targeted at senior nurses/specialist nurses initially to develop a critical mass to change organizational culture. RELEVANCE TO CLINICAL PRACTICE: Pertinent for senior nurses responsible for developing children's nursing practice and services for children in acute settings. PMID- 17335531 TI - The prevalence of enduring postnatal perineal morbidity and its relationship to type of birth and birth risk factors. AB - AIMS AND OBJECTIVES: To investigate the prevalence of perineal morbidity at 12 months postnatal and its relationship to type of birth and birth risk factors. BACKGROUND: It is well documented that women endure short-term postnatal perineal morbidity following childbirth (e.g. incontinence, perineal pain and sexual morbidity). However, to date, very little research has been carried out on the long-term effects of perineal morbidity and its relationship to the type of birth the women experienced and other birth risk factors (e.g. ethnic origin, age, parity, length of labour, epidural anaesthesia). DESIGN: A retrospective, cross sectional community survey of postnatal women within two maternity units in Birmingham. METHODS: A total population sample of 2,100 women were surveyed using a self-administered postal questionnaire. The questionnaire included self assessment of perineal pain, perineal healing, urinary incontinence, flatus incontinence, faecal incontinence, sexual morbidity and dyspareunia. Demographic details, type of birth and birth risk factors were taken from the hospital's computerized maternity information system. RESULTS: Four hundred and eighty-two women responded to the questionnaire (23.3%). Overall, a high level of enduring perineal morbidity was reported with 87% complaining of at least one index of morbidity. Instrumental births were associated with higher levels of certain types of perineal morbidity than women following a caesarean section or normal vaginal birth (stress and urge urinary incontinence, flatus incontinence, sexual morbidity and dyspareunia). In particular, women following a forceps birth reported higher levels of morbidity than normal or ventouse birth (continual, stress and urge urinary incontinence and flatus incontinence), even when comparing with the same degree of perineal trauma. Increasing age, increasing birth weight, length of labour and particularly Asian ethnic origin were also identified as risk factors for certain types of perineal morbidity. CONCLUSIONS: The study concludes that enduring perineal morbidity in women following childbirth is common, especially with women following a forceps birth and certain birth risk factors (i.e. age, ethnic origin, length of labour and birth weight). RELEVANCE TO CLINICAL PRACTICE: These findings highlight the need for further research and provide a number of challenges for health-care services and health care professionals. PMID- 17335532 TI - The effects of different maternal positions on non-stress test: an experimental study. AB - AIMS AND OBJECTIVES: To determine the effects of different maternal positions on non-stress test results and the preferences of mothers for involving positions. BACKGROUND: The non-stress test (NST) has become a common tool in diagnosing fetal risks. The major problem encountered in the application of the non-stress test has been obtaining erroneous non-reactive non-stress test results when, indeed, the fetus is healthy and oxygenation is sufficient. STUDY DESIGN: Experiment design with randomly assigned four positions: supine, left lateral, semi-fowler and sitting up. The sample included 408 women in a university hospital in Turkey. Women were randomly assigned to four groups in equal numbers of 102. Data collection and analysis. Data were collected through two instruments: Demographic and Pregnancy History Form and NST tracing. Main outcome measures were percentage of reactive NST and number of minutes for reactivity in each position. RESULTS: There were significant (P < 0.05) differences among four groups. Supine position showed the least fetal reactivity. In terms of time to reactivity, there were no statistically significant differences. Qualitative data showed that pregnant women were least comfortable in supine position reporting back pain and shortening of breath. CONCLUSION: Supine position yields the lowest non-reactivity in tandem with physical discomfort such as back pain and difficulty in breathing. RELEVANCE TO CLINICAL PRACTICE: Sitting up, semi-fowler and left lateral positions are recommended to be used during the non-stress test. In addition, the preferences of the pregnant women should be determined before the test to minimize discomfort which, when it occurs, may signal physiological alterations experienced during the test. PMID- 17335533 TI - Health promotion for people aged over 65 years in hospitals: nurses' perceptions about their role. AB - AIM: To identify nurses' beliefs about health promotion and its delivery in routine care of people aged over 65 years. BACKGROUND: Regardless of age, health promotion interventions can enhance health and, in general, older people are motivated to take such preventive action. The National Service Framework for Older People sets the promotion of healthy living as a standard for UK National Health Service Trusts. However, the delivery of health promotion is 'haphazard'; patients aged over 65 years rarely report receiving health promotion, and reports from nurses suggest they are unsure how to deliver effective health promotion. METHOD: A theory-based survey of all nurses working in a department specializing in the care of people aged over 65 years, 41% of questionnaires were returned. RESULTS: The majority of nurses identified examples of health promotion and 88% judged health promotion to be effective and worthwhile. Three quarters of the sample viewed health promotion as part of their role and most of the respondents were confident in their ability to provide health promotion. However, the respondents also reported that health promotion was not appropriate for all their patients and considered it an increasingly difficult task as people got older. Organizational barriers to the routine provision of health promotion were identified. CONCLUSION: Nurses working on wards for people aged over 65 years are mostly positive about integrating health promotion into their everyday work. However, for health promotion to be routinely implemented, all nursing staff need to feel confident in undertaking the task and believe it is worthwhile. Health promotion needs to be awarded greater importance by hospital management to ensure that it does not conflict with other work priorities. Until this happens the provision of health promotion in hospitals will remain sporadic and lack conviction. RELEVANCE TO CLINICAL PRACTICE: With an increasing older population nurses need to be confident and proficient at implementing health promotion to patients aged over 65 years. This survey demonstrates that nurses need more training and support to achieve this. PMID- 17335534 TI - Findings from non-participant observational data concerning health promoting nursing practice in the acute hospital setting focusing on generalist nurses. AB - AIM: This paper reports on the non-participant observational findings from a study, which examined hospital-based nurses' health promoting nursing practice in an acute setting. BACKGROUND: Nurses are considered to have a key role in health promotion. However, the development of the role of the generalist hospital-based nurse in health promotion has been slow and is not well-understood. METHOD: The conceptual framework used was based on the Ottawa Charter (WHO 1986). A single qualitative embedded case study, employing data source and methodological triangulation was used. A framework for identifying nurse's use of health promotion methods was developed and used to collect non-participant observations on a purposive sample of eight nurses working on an acute hospital ward. Following the observations a semi structured one-to-one interview was conducted with each observed nurse. One randomly selected patient that the observed nurse had cared for during the observations was also interviewed. Qualitative data analysis based on the work of Miles and Huberman was employed. RESULTS: Two categories were identified 'health promotion strategies and content' and 'patient participation'. The findings indicated that, overall, the strategies used by nurses to promote health were prescriptive and individualistic. The main strategy observed was information giving and the content was 'preparatory information'. Predominantly, nurses practised traditional health education. Overall, patient participation was limited to minor personal aspects of care as nurses focused on the routine and getting the tasks completed. There was no evidence of a ward culture which valued health promotion. CONCLUSIONS: Ward managers are key in creating a culture for health promotion. A review of the methods of organizing nursing care is warranted. RELEVANCE TO CLINICAL PRACTICE: Nursing programmes must highlight health promotion as integral to practice and emphasis the socio political dimensions of health promotion. PMID- 17335535 TI - Examining the correspondence of theoretical and real interpretations of health promotion. AB - AIMS AND OBJECTIVES: The aim of the research was to identify how the development of concept analyses have influenced practising nurses' understanding of health promotion. More specifically the aim gives rise to the objective of establishing how they translate their understanding into practice. BACKGROUND: The acknowledgement that nurses are confused about health promotion has led to attempts to define the term through the production of concept analyses, which aim to clarify the term for nursing education, research, policy and practice. DESIGN AND METHODS: A qualitative approach, using semi-structured interviews was undertaken with a purposive sample of 21 district nurses, based throughout Wales. Thematic content analysis was used to order, describe and interpret the data. RESULTS: Generally the respondents gave definitions of health promotion that were confined to the traditional conceptualization of health promotion, comprising actions aimed at changing the behaviour of individuals. These interpretations were translated into practice, where district nurses adopted a mainly reactive and individualistic approach to health promotion. CONCLUSIONS AND RELEVANCE TO CLINICAL PRACTICE: The paper concludes that the more contemporary definitions of health promotion that focus on empowerment, community development and socio political action are yet to reach practising district nurses. Considerable effort is required from educationalists and practitioners if nurses are to include these 'new paradigm' approaches to health promotion in their practice. PMID- 17335536 TI - Health beliefs and expectations implicit in decision-making in a Hong Kong Chinese surgical population. AB - AIMS AND OBJECTIVES: This study was undertaken to explore health beliefs and expectations implicit in decision-making preferences of Chinese patients admitted for a surgical procedure in a regional hospital in Hong Kong. BACKGROUND: Patient participation in decision-making about healthcare options is presently being advocated; however, its nature is complex and inadequately explored and understood. METHOD: Twenty surgical patients, 10 who desired active participation and 10 who desired passive participation, were interviewed about their reasons for their decision-making preference. RESULTS: From thematic analysis of the interviews, 'trust' and 'certainty' emerged as important concepts. Of particular interest is how 'certainty' was construed differently by participants: participants who desired to be passive and have minimal participation in decision making did not focus on 'certainty' as meaning the predictability of the treatment outcome, but rather 'certainty' related to trust and belief in the ability of the doctor to choose the best option for them. Alternatively, participants who desired greater participation in decision-making spoke much more about the 'certainty' of the treatment outcome. CONCLUSIONS: These findings suggest that patients' desire for participation in decision-making about surgery may be related to beliefs, expectations and understanding about certainty. RELEVANCE TO CLINICAL PRACTICE: It could potentially benefit patients if this concept was explored further prior to patients undertaking decisions about undergoing surgery. PMID- 17335537 TI - Chinese women's experiences in coping with urinary incontinence. PMID- 17335538 TI - Commentary on Lambert V & Glacken M (2005) Clinical education facilitators: a literature review. Journal of Clinical Nursing 14, 664-673. PMID- 17335539 TI - Commentary on Nahcivan NO & Demirezen E (2005) Depressive symptomatology among Turkish older adults with low income in a rural community sample. Journal of Clinical Nursing 14, 1232-1240. PMID- 17335540 TI - Commentary on Nairn S, O'Brien E, Traynor V, Williams G, Chapple M & Johnson S (2006) Student nurses' knowledge, skills and attitudes towards the use of portfolios in a school of nursing. Journal of Clinical Nursing15, 1509-1520. PMID- 17335542 TI - An integrated model for the effect of budesonide on ACTH and cortisol in healthy volunteers. AB - AIMS: Budesonide, a glucocorticosteroid, is used as a first-line treatment for asthma. The aim of the study was to develop a PK/PD model for the effect of budesonide on ACTH and cortisol. METHODS: The modelling data were generated by conducting a single-blind, randomized, placebo-controlled cross-over study. Ten healthy volunteers inhaled placebo (Placebo Turbohaler) and 1600 microg budesonide (Pulmicort Turbohaler), with a wash-out period of 7 days between treatments. Baseline concentrations of cortisol and ACTH were measured after placebo treatment and concentrations of cortisol, ACTH and budesonide were assessed after budesonide treatment. A one-compartment disposition model was used for budesonide disposition. Based on indirect response models, two types of models, distinguishing between production driven by a sum of cosine functions and production driven by surges, were used in parallel to describe the data. RESULTS: The surge-based approach was the most appropriate, based on goodness-of-fit, objective function values and number of parameters. The surge-based model that integrated both ACTH and cortisol data was chosen as the final model. The estimated half-lives of endogenous ACTH and cortisol were 9 and 113 min, respectively. The budesonide and ACTH concentrations producing 50% of the maximal response (IC(50) and A(50)) were 0.325 microg l(-1) and 4.96 pmol l(-1). CONCLUSIONS: The present PK/PD model of the effect of budesonide on ACTH and cortisol can serve as a tool for further understanding of the hypothalamic pituitary-adrenal (HPA) axis and be useful in the development of drugs interacting with the axis. PMID- 17335543 TI - Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis. AB - Cryptosporidium is a common cause of gastroenteritis and is associated with severe life-threatening illness among immunocompromised individuals. This review aimed to assess the efficacy of interventions for the treatment and prevention of cryptosporidiosis among immunocompromised patients. A search of Medline, Embase and other electronic databases was carried out up to August 2005. Two reviewers independently extracted data and assessed study quality. The relative risk for each intervention was calculated. Seven trials involving 169 participants were included. Nitazoxanide and paramomycin were associated with a relative risk (RR) of reduction in the duration and frequency of diarrhoea of 0.83 [95% confidence interval (CI) 0.36, 1.94] and 0.74 (95% CI 0.42, 1.31), respectively, showing no evidence of effectiveness. Nitazoxanide led to significant evidence of oocyst clearance compared with placebo with a RR of 0.52 (95% CI 0.30, 0.91). The effect was not significant for HIV-seropositive participants (RR 0.71, 95% CI 0.36, 1.37). HIV-seronegative participants on nitazoxanide had a significantly higher relative risk of achieving parasitological clearance of 0.26 (95% CI 0.09, 0.80) based on a single study. No other intervention was associated with either a reduction in diarrhoea, mortality or a significant parasitological response. This review confirms the absence of evidence for effective agents in the management of cryptosporidiosis. The results indicate that nitaxozanide reduces load of parasites and may be useful in immunocompetent individuals. The absence of effective therapy highlights the importance of preventive interventions in this group of patients. PMID- 17335544 TI - Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity. AB - AIMS: To examine retrospectively the relationship between DPD phenotype/genotype and the intensity of 5FU toxicity. METHODS: One hundred and thirty-one case reports (81 women, 50 men) with 5FU-related toxicity were analyzed. RESULTS: The lower the DPD activity (10-504 pmol min(-1) mg(-1)), the higher the toxicity grade was scored (P < 0.01). Toxicity-related deaths occurred in nine patients (eight women) who significantly expressed lower DPD activity than other patients. Two of the deceased patients had normal DPD activity. The IVS14+1G>A mutation, analyzed in 93 patients, was detected in two patients (nonlethal toxicity). CONCLUSIONS: The IVS14+1G>A mutation may not help prevent toxicity and patients with normal DPD activity may develop life-threatening 5FU toxicity. PMID- 17335545 TI - Age dependent systemic exposure to inhaled salbutamol. AB - AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing a dose on a microg kg(-1) basis caused reduced systemic exposure in young children (Y) compared with older children (O) (C(max-microg kg(-1)-adjusted) Y : O ratio (95%CI) = 0.55 (0.47, 0.65)) whereas a fixed nominal dose irrespective of age caused increased exposure in young children (C(max) Y : O ratio (95%CI) = 1.7 (1.3, 2.2)). CONCLUSIONS: For similar systemic exposure, dosing should be adjusted to age or size but not on a fixed microg kg(-1) basis, which may lead to unnecessary suboptimal dosing. PMID- 17335546 TI - Effect of renal impairment on the pharmacokinetics of bupropion and its metabolites. AB - AIMS: To investigate the effect of kidney disease on bupropion pharmacokinetics and on cytochrome P450 (CYP) 2B6 activity as measured by bupropion hydroxylation. METHODS: In an open parallel group study, 17 healthy, nonsmoking subjects and 10 patients with impaired kidney function received a single 150 mg oral dose of sustained release bupropion. Plasma concentrations of bupropion and its metabolites were measured for up to 72 h. Subjects were genotyped for the CYP2B6 SNPs 1459 C>T, 785 A>G and 516 G>T. RESULTS: Bupropion AUC was 126% higher (P < 0.0001, 95% CI +72%, +180%), C(max) 86% higher (P = 0.001, 95% CI +40%, +131%), CL/F 63% lower (P = 0.001, 95% CI -29%, -96%), and t(1/2) 140% longer (P = 0.001, 95% CI +76%, +204%) in renally impaired patients. However, only minor changes were detected in the concentrations of the metabolites. In renally impaired subjects the hydroxybupropion : bupropion AUC ratio was decreased by 66% (P = < 0.0001, 95% CI -19%, -114%) and the hydrobupropion : bupropion AUC ratio by 69% (P = 0.001, 95% CI +8%, -146%) compared with controls. CONCLUSIONS: The CL/F of bupropion was significantly lower in subjects with renal impairment. Because the principal metabolites of bupropion possess similar pharmacological activity to the parent compound, dosage recommendations for patients with renal impairment cannot be given. A direct effect of renal impairment on CYP2B6 activity could not be demonstrated by the present study design. PMID- 17335547 TI - Elevated levels of plasma matrix metalloproteinase-9 in patients with atopic dermatitis: a pilot study. AB - Matrix metalloproteinase (MMP)-9 has been shown to play a role in the infiltration of inflammatory cells in various tissues. It is thus part of the pathogenesis of many inflammatory diseases, including asthma and allergic rhinitis/conjunctivitis. We compared plasma MMP-9 levels of 20 patients with atopic dermatitis (AD) with that of 17 control subjects. Additional outcome parameters consisted of the modified objective SCORing Atopic Dermatitis and the Three Item Severity score in patients, and peripheral blood leucocytes and eosinophils in both groups. Plasma MMP-9 levels were found to be significantly higher in patients compared with controls, supporting a role for MMP-9 in the pathogenesis of AD. PMID- 17335548 TI - A bullous dermatosis in an infant. PMID- 17335549 TI - Discovering the cause helps the cure. PMID- 17335551 TI - Primary melanoma of the umbilicus appearing as omphalitis. PMID- 17335552 TI - Comparison of hydration, sebum and pH values in clinically normal skin of patients with atopic dermatitis and healthy controls. PMID- 17335553 TI - The importance of KMR completion for dermatology income in secondary care in the UK. AB - BACKGROUND: In the UK, a Korner Medical Record (KMR) document is completed for each inpatient discharged from hospital. The number and type of medical conditions entered onto this record are used to determine the income the department will receive for that individual patient. AIMS: We set out to audit the accuracy of the KMR documentation of our dermatology ward, and to assess what impact improving these records would have on the department's income. The audit standard was that KMRs should be completed accurately and contain all of the relevant information. METHODS: KMRs from May 2005, which had been completed initially by the ward clerk, and later by the junior medical staff, were reviewed. They were then completed by the main auditor, who had received training in KMR completion from the coding department. All three sets of KMRs were reviewed by the coding officer, and their respective income calculated. RESULTS: In total, 20 patients were discharged from the dermatology ward during April 2005. The main diagnosis given for two patients was initially incorrect, and in another eight cases it could have been more accurate than was originally documented. The total number of comorbid or 'secondary' diagnoses (for all 20 patients) reported by the ward clerk was 5. Junior staff added a further 36 secondary diagnoses. The main auditor identified an additional 35 secondary diagnoses. In total, an extra pound 9211 would have been paid to the department if KMRs had been completed by the main auditor rather than the ward clerk. On an annual basis, a potential pound 110,532 would remain unclaimed if KMR completion continued to be performed by the ward clerk. CONCLUSIONS: This audit shows that KMR completion is inadequate when performed by a nonmedical practitioner. Training of medical staff in KMR completion by the coding department also significantly increases the accuracy and completeness of documentation. Dermatologists of all grades need to be aware of the importance and process of KMR completion, and routine training of medical staff by their coding department in KMR completion is recommended. PMID- 17335554 TI - Administration of anti-type II collagen antibody sustains footpad swelling of mice caused by a delayed-type hypersensitivity reaction and induces severe arthritis. AB - Delayed-type hypersensitivity (DTH) is an immune reaction induced by antigen. In the mice footpads at which DTH is elicited, transient swellings which usually peaks at 24-48 h after the antigen challenge are observed. We found that the footpad swellings of mice are sustained for at least 7 days after the antigen challenge if the mice were injected with anti-type II collagen monoclonal antibody (anti-CII MoAb) before the antigen challenge. A histological section of the swelled hindpaw revealed that severe joint inflammation and bone destruction was induced. These features were not observed in the footpads of the DTH-induced mice. Analysis of the inflammatory reaction induced by both the DTH and the anti CII MoAb injection, here named as DTH arthritis, revealed the following: (1) DTH arthritis is elicited in an antigen-specific manner; and (2) the development of DTH arthritis is mediated by antigen-specific T cells, especially CD4+ T cells. PMID- 17335555 TI - Protective role of mannan-binding lectin in a murine model of invasive pulmonary aspergillosis. AB - Innate immune molecules such as lung collectins and serum pentraxins have evolved as important host defence proteins against Aspergillus fumigatus, a medically important opportunistic fungal pathogen. Mannan-binding lectin (MBL), an opsonin and lectin complement pathway activator, constitutes another vital player of innate immunity against several pathogenic organisms in the serum. Studies have reported significant binding of MBL to A. fumigatus; however, the protective role of MBL against A. fumigatus-mediated invasive disease remains elusive. Henceforth, we investigated the contribution of externally administered recombinant human (rh) MBL towards anti-fungal defence in invasive pulmonary aspergillosis (IPA) by in vivo and in vitro studies. In murine models of IPA with corticosteroid-induced immunosuppression, rhMBL-treated mice showed 80% survival compared to untreated IPA mice with no survivors. Treated IPA mice also showed a marked increase in tumour necrosis factor (TNF)-alpha and interleukin (IL)-1alpha and a significant decrease in pulmonary fungal hyphae and IL-10. In vitro, rhMBL bound A. fumigatus conidia showed a dose-dependent increase in the deposition of C4b, the first product of the lectin pathway. There was an enhanced uptake of A. fumigatus conidia by the polymorphonuclear cells (PMNs) in the presence of rhMBL that increased further in the presence of MBL supplemented with MBL-deficient serum. However, an increase in the oxidative burst of PMNs and A. fumigatus killing were observed only when MBL was supplemented with MBL-deficient serum. The study suggests a therapeutic role of ex vivo-administered MBL in host defence against aspergillosis, possibly through MBL-mediated complement activation and other protective mechanisms aimed both directly at the pathogen, and indirectly through modulation of the host inflammatory responses. PMID- 17335556 TI - Mannan-binding lectin may facilitate the clearance of circulating immune complexes--implications from a study on C2-deficient individuals. AB - Deficiency of both mannan-binding lectin (MBL) and complement components C4 and C2 has been associated with increased risk of systemic lupus erythematosus (SLE). MBL can activate the complement system either through C4 and C2 or directly through C3. Circulating immune complexes (CICs) are believed to play a pathogenic role in SLE and MBL has been shown to bind certain forms of immunoglobulins, including IgM, IgG and IgA. Thus, MBL might promote CIC clearance. In order to evaluate this, six individuals with non-functional classical pathway due to the rare homozygous C2 deficiency were chosen, as the classical pathway is known to have a fundamental role in CIC clearance. Four of the six C2-deficient individuals had SLE, two of whom also had MBL deficiency. MBL serum levels and genotypes were compared with the serum levels of CICs, as measured by their content of kappa, lambda, IgM, IgA, IgG and C3 opsonization. The C2-deficient individuals had higher serum levels of CICs than 16 healthy controls (P < 0.0001). Furthermore, an inverse association was observed between MBL and CIC levels in the C2-deficient individuals, which was strongest for IgM-CICs (r = - 0.84, P = 0.037). Moreover, C3 opsonization of the CICs correlated positively with MBL levels in the C2-deficient individuals (r = 0.89, P = 0.017). In conclusion, individuals with C2 deficiency have increased levels of CICs and MBL may facilitate their clearance. Defective CIC clearance might partly explain the increased risk of SLE associated with low MBL. PMID- 17335557 TI - Proteins specifically hyperexpressed in a coeliac disease patient with aberrant T cells. AB - An aberrant T cell population is the basis for diagnosis of refractory coeliac disease and determines the risk of enteropathy-associated T cell lymphoma. This disease is serious with a poor survival. Pathogenetic mechanisms sustaining aberrant T cell proliferation remain unknown. Recently, alemtuzumab has been proposed as a promising new approach to treat these patients. Only few single cases have been tested at present; nevertheless, in all the cases a clinical improvement was observed. However, whether intraepithelial lymphocytes have been targeted effectively by alemtuzumab is still debated. This study reports, using two-dimensional difference gel electrophoresis (2D DIGE), hyperexpressed proteins associated specifically with aberrant T cells found in a patient with coeliac disease by comparison of the protein expression of this sample with that of patients with coeliac disease and polyclonal T cells or with control subjects. The data demonstrated a significantly higher expression of IgM, apolipoprotein C III and Charcot-Leyden crystal proteins in a duodenal biopsy specimen of the patient with clonal T cells compared with that of other patients. These preliminary results allow hypothesizing different clinical effects of alemtuzumab in patients with coeliac disease and aberrant T cell proliferation, because as well as the probable effect on T cells, alemtuzumab could exert its effect by acting on inflammatory associated CD52(+) IgM(+) B cells and eosinophil cells, known to produce IgM and Charcot-Leyden crystal proteins, that we demonstrated to be altered in this patient. The results also emphasize the possible association of apolipoprotein with aberrant T cell proliferation. PMID- 17335558 TI - Toll-like receptor 4-dependent recognition of structurally different forms of chemically synthesized lipid As of Porphyromonas gingivalis. AB - Porphyromonas gingivalis is a Gram-negative anaerobic oral black-pigmented bacterium closely associated with chronic periodontitis. Lipopolysaccharide (LPS) derived from P. gingivalis is shown to be unusual because the LPS contains a greater number of lipid A species, such as tri-, tetra-, and/or penta-acylated lipid As. In this study, a lipid A possessing penta-fatty acyl chains derived from P. gingivalis strain 381 (compound PG-381-5FA) was synthesized, and examined for its immunobiological activities, compared with a tri-acylated lipid A (compound PG-381-3FA) synthesized previously. Compound PG-381-5FA, similar to compound PG-381-3FA, demonstrated weaker activity in a Limulus test as compared with Escherichia coli-type synthetic lipid A (compound 506). Compound PG-381-5FA, followed by compound PG-381-3FA, induced KC, interleukin-6, and tumour necrosis factor-alpha production in peritoneal macrophages from LPS-responsive C3H/HeN mice, but not in those from LPS-hyporesponsive C3H/HeJ mice. Furthermore, compound PG-381-5FA, as well as compound PG-381-3FA, activated nuclear factor kappaB via Toll-like receptor (TLR)4/mD-2, but not TLR2, in a manner similar to compound 506, and worked as an antagonist for compound 506-induced cell activation. In the case of human peripheral blood mononuclear cells, compound PG 381-5FA showed much stronger IL-6-inducing activity than compound PG-381-3FA. The present results demonstrate that the chemical synthesis of a penta-acylated lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, is attributable to immune cell activation through TLR4, similar to that of compound 506. PMID- 17335559 TI - Respiratory syncytial virus replication is prolonged by a concomitant allergic response. AB - Epidemiological studies show an association between early exposure to respiratory syncytial virus (RSV) and the development or exacerbation of asthma. This idea is supported by studies in mice that demonstrate worsened airway hyper-reactivity (AHR) when RSV-infected animals are exposed to allergen. The effect of allergen on RSV disease, however, has not been reported. Cotton rats (Sigmodon hispidus) that have been used as a model to study RSV pathogenesis were sensitized to extracts of Aspergillus fumigatus (Af), a common household mould. The allergic response to Af included eosinophilia, formation of granulomas and induction of Th2 type cytokines. RSV infection prior to allergen challenge resulted in exacerbation of the inflammatory response as well as increased airway responsiveness to methacholine. The exacerbated response was indeed dependent on virus replication. Virus replication in turn was influenced by the allergic response, with persistence in the noses for 2 days longer in animals challenged with allergen. This diminished clearance corresponded to decreased induction of mRNA for IFN-gamma, a Th1-type cytokine that is characteristic of viral infection. Treatment of RSV-infected Af-challenged animals with recombinant IFN gamma reduced the allergic inflammatory response as well as the relative levels of Th1 and Th2 cytokine mRNA. However, this treatment did not reduce airway reactivity, showing that these pathologic and physiologic measures of exacerbated disease are independent. We speculate that the reciprocal effect of the allergic response on viral immunity may benefit the host by limiting exacerbation of physiologic responses that are IFN-gamma-dependent. PMID- 17335560 TI - Quantification of the tissue-culture induced variation in barley (Hordeum vulgare L.). AB - BACKGROUND: When plant tissue is passaged through in vitro culture, many regenerated plants appear to be no longer clonal copies of their donor genotype. Among the factors that affect this so-called tissue culture induced variation are explant genotype, explant tissue origin, medium composition, and the length of time in culture. Variation is understood to be generated via a combination of genetic and/or epigenetic changes. A lack of any phenotypic variation between regenerants does not necessarily imply a concomitant lack of genetic (or epigenetic) change, and it is therefore of interest to assay the outcomes of tissue culture at the genotypic level. RESULTS: A variant of methylation sensitive AFLP, based on the isoschizomeric combinations Acc65I/MseI and KpnI/MseI was applied to analyze, at both the sequence and methylation levels, the outcomes of regeneration from tissue culture in barley. Both sequence mutation and alteration in methylation pattern were detected. Two sets of regenerants from each of five DH donor lines were compared. One set was derived via androgenesis, and the other via somatic embryogenesis, developed from immature embryos. These comparisons delivered a quantitative assessment of the various types of somaclonal variation induced. The average level of variation was 6%, of which almost 1.7% could be accounted for by nucleotide mutation, and the remainder by changes in methylation state. The nucleotide mutation rates and the rate of epimutations were substantially similar between the andro- and embryo derived sets of regenerants across all the donors. CONCLUSION: We have developed an AFLP based approach that is capable of describing the qualitative and quantitative characteristics of the tissue culture-induced variation. We believe that this approach will find particular value in the study of patterns of inheritance of somaclonal variation, since non-heritable variation is of little interest for the improvement of plant species which are sexually propagated. Of significant biological interest is the conclusion that the mode of regeneration has no significant effect on the balance between sequence and methylation state change induced by the tissue culture process. PMID- 17335561 TI - Role-play for medical students learning about communication: guidelines for maximising benefits. AB - BACKGROUND: Role-play is widely used as an educational method for learning about communication in medical education. Although educational theory provides a sound rationale for using this form of simulation, there is little published evidence for its effectiveness. Students' prior experiences of role-play may influence the way in which they engage in this method. This paper explores students' experiences with the aim of producing guidelines for maximising the benefits of role-play within this learning context. METHODS: First-year undergraduate medical students participated in a role-play session as part of their communication programme. Before and after the session, students completed questionnaires. In the pre-session questionnaire, students were asked about their experiences of role-play and asked to identify helpful and unhelpful elements. Immediately after the session, students answered similar questions in relation to the role-play activity they had just completed. Descriptive statistics were used to analyse quantitative data and qualitative data was thematically analysed. RESULTS: 284 students completed evaluation forms. Although 63 (22.2%) had prior unhelpful experiences, most students (n = 274; 96.5%) found this experience helpful. Summary findings were that students reported the key aspects of helpful role-play were opportunities for observation, rehearsal and discussion, realistic roles and alignment of roles with other aspects of the curriculum. Unhelpful aspects were those that evoked strong negative emotional responses and factors that contributed to a lack of realism. CONCLUSION: Role-play was valued by students in the acquisition of communication skills even though some had prior unhelpful experiences. Guidelines for effective role-play include adequate preparation, alignment of roles and tasks with level of practice, structured feedback guidelines and acknowledgment of the importance of social interactions for learning. PMID- 17335562 TI - Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. AB - BACKGROUND: Community-acquired pneumonia (CAP) is the most frequent infection related cause of death. The reference standard to diagnose CAP is a new infiltrate on chest radiograph in the presence of recently acquired respiratory signs and symptoms. This study aims to evaluate the diagnostic and prognostic accuracy of clinical signs and symptoms and laboratory biomarkers for CAP. METHODS: 545 patients with suspected lower respiratory tract infection, admitted to the emergency department of a university hospital were included in a pre planned post-hoc analysis of two controlled intervention trials. Baseline assessment included history, clinical examination, radiography and measurements of procalcitonin (PCT), highly sensitive C-reactive protein (hsCRP) and leukocyte count. RESULTS: Of the 545 patients, 373 had CAP, 132 other respiratory tract infections, and 40 other final diagnoses. The AUC of a clinical model including standard clinical signs and symptoms (i.e. fever, cough, sputum production, abnormal chest auscultation and dyspnea) to diagnose CAP was 0.79 [95% CI, 0.75 0.83]. This AUC was significantly improved by including PCT and hsCRP (0.92 [0.89 0.94]; p < 0.001). PCT had a higher diagnostic accuracy (AUC, 0.88 [0.84-0.93]) in differentiating CAP from other diagnoses, as compared to hsCRP (AUC, 0.76 [0.69-0.83]; p < 0.001) and total leukocyte count (AUC, 0.69 [0.62-0.77]; p < 0.001). To predict bacteremia, PCT had a higher AUC (0.85 [0.80-0.91]) as compared to hsCRP (p = 0.01), leukocyte count (p = 0.002) and elevated body temperature (p < 0.001). PCT, in contrast to hsCRP and leukocyte count, increased with increasing severity of CAP, as assessed by the pneumonia severity index (p < 0.001). CONCLUSION: PCT, and to a lesser degree hsCRP, improve the accuracy of currently recommended approaches for the diagnosis of CAP, thereby complementing clinical signs and symptoms. PCT is useful in the severity assessment of CAP. PMID- 17335563 TI - Methodological standards in non-inferiority AIDS trials: moving from adherence to compliance: response. PMID- 17335564 TI - Differential expression of CD10 in prostate cancer and its clinical implication. AB - BACKGROUND: CD10 is a transmembrane metallo-endopeptidase that cleaves and inactivates a variety of peptide growth factors. Loss of CD10 expression is a common, early event in human prostate cancer; however, CD10 positive cancer cells frequently appear in lymph node metastasis. We hypothesize that prostate tumors expressing high levels of CD10 have a more aggressive biology with an early propensity towards lymph node metastasis. METHODS: Eighty-seven patients, 53 with and 34 without pathologically organ confined prostate cancer at the time of radical prostatectomy (RP), were used for the study. Fourteen patients with lymph node metastasis found at the time of surgery were identified and included in this study. Serial sections from available frozen tumor specimens in OCT were processed for CD10 immunohistochemistry. Cancer glands were graded for the presence and intensity of CD10 staining, and overall percentage of glands staining positive was estimated. Clinical characteristics including pre- and post operative PSA and Gleason score were obtained. A similar study as a control for the statistical analysis was performed with CD13 staining. For statistical analysis, strong staining was defined as > 20% positivity based on the observed maximum separation of the cumulative distributions. RESULTS: CD10 expression significantly correlated with Gleason grade, tumor stage, and with pre-operative serum PSA. Seventy percent of RP specimens from patients with node metastasis showed strong staining for CD10, compared to 30% in the entire cohort (OR = 3.4, 95% CI: 1.08-10.75, P = 0.019). Increased staining for CD10 was associated with PSA recurrence after RP. CD13 staining did not correlate significantly with any of these same clinical parameters. CONCLUSION: These results suggest that the expression of CD10 by prostate cancer corresponds to a more aggressive phenotype with a higher malignant potential, described histologically by the Gleason score. CD10 offers potential clinical utility for stratifying prostate cancer to predict biological behavior of the tumor. PMID- 17335565 TI - Homeopathic and conventional treatment for acute respiratory and ear complaints: a comparative study on outcome in the primary care setting. AB - BACKGROUND: The aim of this study was to assess the effectiveness of homeopathy compared to conventional treatment in acute respiratory and ear complaints in a primary care setting. METHODS: The study was designed as an international, multi centre, comparative cohort study of non-randomised design. Patients, presenting themselves with at least one chief complaint: acute (< or = 7 days) runny nose, sore throat, ear pain, sinus pain or cough, were recruited at 57 primary care practices in Austria (8), Germany (8), the Netherlands (7), Russia (6), Spain (6), Ukraine (4), United Kingdom (10) and the USA (8) and given either homeopathic or conventional treatment. Therapy outcome was measured by using the response rate, defined as the proportion of patients experiencing 'complete recovery' or 'major improvement' in each treatment group. The primary outcome criterion was the response rate after 14 days of therapy. RESULTS: Data of 1,577 patients were evaluated in the full analysis set of which 857 received homeopathic (H) and 720 conventional (C) treatment. The majority of patients in both groups reported their outcome after 14 days of treatment as complete recovery or major improvement (H: 86.9%; C: 86.0%; p = 0.0003 for non-inferiority testing). In the per-protocol set (H: 576 and C: 540 patients) similar results were obtained (H: 87.7%; C: 86.9%; p = 0.0019). Further subgroup analysis of the full analysis set showed no differences of response rates after 14 days in children (H: 88.5%; C: 84.5%) and adults (H: 85.6%; C: 86.6%). The unadjusted odds ratio (OR) of the primary outcome criterion was 1.40 (0.89-2.22) in children and 0.92 (0.63-1.34) in adults. Adjustments for demographic differences at baseline did not significantly alter the OR. The response rates after 7 and 28 days also showed no significant differences between both treatment groups. However, onset of improvement within the first 7 days after treatment was significantly faster upon homeopathic treatment both in children (p = 0.0488) and adults (p = 0.0001). Adverse drug reactions occurred more frequently in adults of the conventional group than in the homeopathic group (C: 7.6%; H: 3.1%, p = 0.0032), whereas in children the occurrence of adverse drug reactions was not significantly different (H: 2.0%; C: 2.4%, p = 0.7838). CONCLUSION: In primary care, homeopathic treatment for acute respiratory and ear complaints was not inferior to conventional treatment. PMID- 17335566 TI - Bounds on the distribution of the number of gaps when circles and lines are covered by fragments: theory and practical application to genomic and metagenomic projects. AB - BACKGROUND: The question of how a circle or line segment becomes covered when random arcs are marked off has arisen repeatedly in bioinformatics. The number of uncovered gaps is of particular interest. Approximate distributions for the number of gaps have been given in the literature, one motivation being ease of computation. Error bounds for these approximate distributions have not been given. RESULTS: We give bounds on the probability distribution of the number of gaps when a circle is covered by fragments of fixed size. The absolute error in the approximation is typically on the order of 0.1% at 10x coverage depth. The method can be applied to coverage problems on the interval, including edge effects, and applications are given to metagenomic libraries and shotgun sequencing. PMID- 17335567 TI - The Facioscapulohumeral muscular dystrophy region on 4qter and the homologous locus on 10qter evolved independently under different evolutionary pressure. AB - BACKGROUND: The homologous 4q and 10q subtelomeric regions include two distinctive polymorphic arrays of 3.3 kb repeats, named D4Z4. An additional BlnI restriction site on the 10q-type sequence allows to distinguish the chromosomal origin of the repeats. Reduction in the number of D4Z4 repeats below a threshold of 10 at the 4q locus is tightly linked to Facioscapulohumeral Muscular Dystrophy (FSHD), while similar contractions at 10q locus, are not pathogenic. Sequence variations due to the presence of BlnI-sensitive repeats (10q-type) on chromosome 4 or viceversa of BlnI-resistant repeats (4q-type) on chromosome 10 are observed in both alleles. RESULTS: We analysed DNA samples from 116 healthy subiects and 114 FSHD patients and determined the size distributions of polymorphic 4q and 10q alleles, the frequency and the D4Z4 repeat assortment of variant alleles, and finally the telomeric sequences both in standard and variant alleles. We observed the same frequency and types of variant alleles in FSHD patients and controls, but we found marked differences between the repeat arrays of the 4q and 10q chromosomes. In particular we detected 10q alleles completely replaced by the 4q subtelomeric region, consisting in the whole set of 4q-type repeats and the distal telomeric markers. However the reciprocal event, 10q-type subtelomeric region on chromosome 4, was never observed. At 4q locus we always identified hybrid alleles containing a mixture of 4q and 10q-type repeats. CONCLUSIONS: The different size distribution and different structure of 10q variant alleles as compared with 4q suggests that these loci evolved in a different manner, since the 4q locus is linked to FSHD, while no inheritable disease is associated with mutations in 10qter genomic region. Hybrid alleles on chromosome 4 always retain a minimum number of 4q type repeats, as they are probably essential for maintaining the structural and functional properties of this subtelomeric region. In addition we found: i) several instances of variant alleles that could be misinterpreted and interfere with a correct diagnosis of FSHD; ii) the presence of borderline alleles in the range of 30-40 kb that carried a qA type telomere and were not associated with the disease. PMID- 17335568 TI - Transcriptional analysis of early lineage commitment in human embryonic stem cells. AB - BACKGROUND: The mechanisms responsible for the maintenance of pluripotency in human embryonic stem cells, and those that drive their commitment into particular differentiation lineages, are poorly understood. In fact, even our knowledge of the phenotype of hESC is limited, because the immunological and molecular criteria presently used to define this phenotype describe the properties of a heterogeneous population of cells. RESULTS: We used a novel approach combining immunological and transcriptional analysis (immunotranscriptional profiling) to compare gene expression in hESC populations at very early stages of differentiation. Immunotranscriptional profiling enabled us to identify novel markers of stem cells and their differentiated progeny, as well as novel potential regulators of hESC commitment and differentiation. The data show clearly that genes associated with the pluripotent state are downregulated in a coordinated fashion, and that they are co-expressed with lineage specific transcription factors in a continuum during the early stages of stem cell differentiation. CONCLUSION: These findings, that show that maintenance of pluripotency and lineage commitment are dynamic, interactive processes in hESC cultures, have important practical implications for propagation and directed differentiation of these cells, and for the interpretation of mechanistic studies of hESC renewal and commitment. Since embryonic stem cells at defined stages of commitment can be isolated in large numbers by immunological means, they provide a powerful model for studying molecular genetics of stem cell commitment in the embryo. PMID- 17335569 TI - Tumor necrosis factor alpha and adalimumab differentially regulate CD36 expression in human monocytes. AB - In chronic inflammatory diseases, such as rheumatoid arthritis, inflammation acts as an independent cardiovascular risk factor and the use of anti-inflammatory drugs, such as anti-tumor necrosis factor alpha (anti-TNFalpha), may decrease this risk. The phagocytosis of oxidized low density lipoproteins (LDLs) accumulated in the subendothelium by mononuclear cells influences atherosclerosis and depends on CD36 expression. We investigated the role of TNFalpha and adalimumab, a human anti-TNFalpha monoclonal antibody widely used in human pathology, in CD36 expression in human monocytes. Human monocytes were prepared by adherence from whole-blood buffy-coat fractions from healthy donors. CD36 expression was assessed by RT-PCR and flow cytometry, with various TNFalpha or adalimumab concentrations. Implication of peroxisome proliferator-activated receptor (PPAR)gamma in the regulation of CD36 expression was assessed using specific inhibitor or gel shift assays. The impact of redox signaling was investigated using quantification of reactive oxygen species, antioxidant and a NADPH oxidase inhibitor. The F(ab')2 fragment of adalimumab was isolated and its effect was analyzed. TNFalpha inhibits both CD36 membrane expression and mRNA expression. This inhibition involves a reduction in PPARgamma activation. In contrast, adalimumab increases both CD36 membrane expression and mRNA expression. This induction is independent of the Fc portion of adalimumab and involves redox signaling via NADPH oxidase activation. CD36 expression on human monocytes is inhibited by TNFalpha and independently increased by adalimumab. These data highlight that pro-inflammatory cytokines and their specific neutralization influence the expression of cellular receptors implicated in atherosclerosis. Further studies are needed to investigate the clinical implications of these results in accelerated atherosclerosis observed in rheumatoid arthritis. PMID- 17335570 TI - Origin and diversification of the basic helix-loop-helix gene family in metazoans: insights from comparative genomics. AB - BACKGROUND: Molecular and genetic analyses conducted in model organisms such as Drosophila and vertebrates, have provided a wealth of information about how networks of transcription factors control the proper development of these species. Much less is known, however, about the evolutionary origin of these elaborated networks and their large-scale evolution. Here we report the first evolutionary analysis of a whole superfamily of transcription factors, the basic helix-loop-helix (bHLH) proteins, at the scale of the whole metazoan kingdom. RESULTS: We identified in silico the putative full complement of bHLH genes in the sequenced genomes of 12 different species representative of the main metazoan lineages, including three non-bilaterian metazoans, the cnidarians Nematostella vectensis and Hydra magnipapillata and the demosponge Amphimedon queenslandica. We have performed extensive phylogenetic analyses of the 695 identified bHLHs, which has allowed us to allocate most of these bHLHs to defined evolutionary conserved groups of orthology. CONCLUSION: Three main features in the history of the bHLH gene superfamily can be inferred from these analyses: (i) an initial diversification of the bHLHs has occurred in the pre-Cambrian, prior to metazoan cladogenesis; (ii) a second expansion of the bHLH superfamily occurred early in metazoan evolution before bilaterians and cnidarians diverged; and (iii) the bHLH complement during the evolution of the bilaterians has been remarkably stable. We suggest that these features may be extended to other developmental gene families and reflect a general trend in the evolution of the developmental gene repertoires of metazoans. PMID- 17335571 TI - Silencing of beta-carotene hydroxylase increases total carotenoid and beta carotene levels in potato tubers. AB - BACKGROUND: Beta-carotene is the main dietary precursor of vitamin A. Potato tubers contain low levels of carotenoids, composed mainly of the xanthophylls lutein (in the beta-epsilon branch) and violaxanthin (in the beta-beta branch). None of these carotenoids have provitamin A activity. We have previously shown that tuber-specific silencing of the first step in the epsilon-beta branch, LCY e, redirects metabolic flux towards beta-beta carotenoids, increases total carotenoids up to 2.5-fold and beta-carotene up to 14-fold. RESULTS: In this work, we silenced the non-heme beta-carotene hydroxylases CHY1 and CHY2 in the tuber. Real Time RT-PCR measurements confirmed the tuber-specific silencing of both genes . CHY silenced tubers showed more dramatic changes in carotenoid content than LCY-e silenced tubers, with beta-carotene increasing up to 38-fold and total carotenoids up to 4.5-fold. These changes were accompanied by a decrease in the immediate product of beta-carotene hydroxylation, zeaxanthin, but not of the downstream xanthophylls, viola- and neoxanthin. Changes in endogenous gene expression were extensive and partially overlapping with those of LCY-e silenced tubers: CrtISO, LCY-b and ZEP were induced in both cases, indicating that they may respond to the balance between individual carotenoid species. CONCLUSION: Together with epsilon-cyclization of lycopene, beta-carotene hydroxylation is another regulatory step in potato tuber carotenogenesis. The data are consistent with a prevalent role of CHY2, which is highly expressed in tubers, in the control of this step. Combination of different engineering strategies holds good promise for the manipulation of tuber carotenoid content. PMID- 17335572 TI - Smooth muscle actin and s100p on non germinal centre diffuse large B cell lymphoma are adverse prognostic factors: pilot study. AB - INTRODUCTION: The expression of smooth muscle actin (SMA) and s100p has been identified on an aggressive retro-orbital diffuse large B cell lymphoma (DLBCL) 1. AIM: To assess the prognostic significance of immunohistochemical (IHC) expression of SMA and s100p on DLBCL. MATERIALS AND METHODS: Twenty nine cases diagnosed as DLBCL were first classified into germinal centre (GC) B cell like and non GC origin either activated B cells (ABC) or type 3 based on their immunoreactivity for CD10, bcl-6 and Mum-1. Bcl-2 and MIB-1 as adverse prognostic factors were assessed. SMA and s100p were evaluated and correlated with patients' clinicopathological characteristics. RESULTS: Eleven cases (37.93%) positive for CD10 and/or bcl-6 were classified as GC B cell like subtype, 7 cases positive only for Mum-1 as ABC subtype (24.14%), and 11 cases double positive or negative for bcl-6 and Mum-1 were considered as type 3 (37.93%). Nuclear and cytoplasmic SMA and s100p were expressed in 58.62% and 51.72% of cases respectively and were strongly associated with the non GC like phenotype (p < 0.001 for SMA and p < 0.01 for s100p). SMA and s100p were strongly related to each other (p < 0.001). SMA was closely associated with bcl-2 and MIB-1 (p < 0.01 and p < 0.025 respectively), while s100p was only associated with bcl-2 (p < 0.05). CONCLUSION: SMA and s100p are expressed on non GC DLBCL and appear to be adverse prognostic factors. Future large studies evaluating their significance will be valuable to assess the different subgroups in clinical context. Lastly, this expression may lead to misdiagnosis of non hematopoeitic neoplasm if lymphoid markers are not included in the IHC panel. PMID- 17335573 TI - Mechanism of G1 arrest in the Drosophila eye imaginal disc. AB - BACKGROUND: Most differentiating cells are arrested in G1-phase of the cell cycle and this proliferative quiescence appears important to allow differentiation programmes to be executed. An example occurs in the Drosophila eye imaginal disc, where all cells are synchronized and arrested in G1 phase prior to making a fate choice either to initiate the first round of photoreceptor differentiation or to re-enter one terminal mitosis. RESULTS: We have analysed the mechanism of this temporally regulated G1-phase in order to develop an integrated model of this proliferative regulation. We find that an overlapping set of cell cycle inhibitors combine to form an efficient barrier to cell cycle progression. This barrier depends on both the primary secreted signals that drive retinal development, Dpp and Hh. Each of these has distinct, as well as partially overlapping functions, in ensuring that Cyclin E and dE2F1 are kept in check. Additionally, inhibition of Cyclin A by Roughex is essential, and this regulation is independent of Dpp and Hh. CONCLUSION: One implication of these results is to further support the idea that Cyclin A has important functions in S-phase entry as well as in mitosis. The unexpectedly complex network of regulation may reflect the importance of cells being uniformly ready to respond to the inductive signals that coordinate retinal differentiation. PMID- 17335574 TI - Prevalence of complications of male circumcision in Anglophone Africa: a systematic review. AB - BACKGROUND: There is growing evidence that male circumcision (MC) prevents heterosexual acquisition of HIV by males in sub-Saharan Africa, the region of the world heavily affected by the HIV pandemic. While there is growing support for wide-spread availability and accessibility of MC in Africa, there is limited discussion about the prevalence of physical complications of male circumcision on the continent. METHODS: A systematic literature search and review of articles in indexed journals and conference abstracts was conducted to collect and analyze prevalence of complications of MC in Anglophone sub-Saharan Africa. Information extracted included: indications for MC, complications reported, age of patients and category of circumcisers. RESULTS: There were 8 articles and 2 abstracts that were suitable for the analysis. The studies were not strictly comparable as some reported on a wide range of complications while others reported just a limited list of possible complications. Prevalence of reported complications of MC ranged from 0% to 50.1%. Excluding the study with 50.1%, which was on a series of haemophilia patients, the next highest prevalence of complications was 24.1%. Most of the complications were minor. There was no firm evidence to suggest that MCs performed by physician surgeons were associated with lower prevalence of complications when compared with non-physician health professionals. CONCLUSION: The available data are inadequate to obtain a reasonable assessment of the prevalence of complications of MC in sub-Saharan Africa. Some of the available studies however report potentially significant prevalence of complications, though of minor clinical significance. This should be considered as public health policy makers consider whether to scale-up MC as an HIV preventative measure. Decision for the scale-up will depend on a careful cost-benefit assessment of which physical complications are certainly an important aspect. There is need for standardized reporting of complications of male circumcision. PMID- 17335575 TI - The AIDS and Cancer Specimen Resource: role in HIV/AIDS scientific discovery. AB - The AIDS Cancer and Specimen Resource (ACSR) supports scientific discovery in the area of HIV/AIDS-associated malignancies. The ACSR was established as a cooperative agreement between the NCI (Office of the Director, Division of Cancer Treatment and Diagnosis) and regional consortia, University of California, San Francisco (West Coast), George Washington University (East Coast) and Ohio State University (Mid-Region) to collect, preserve and disperse HIV-related tissues and biologic fluids and controls along with clinical data to qualified investigators. The available biological samples with clinical data and the application process are described on the ACSR web site. The ACSR tissue bank has more than 100,000 human HIV positive specimens that represent different processing (43), specimen (15), and anatomical site (50) types. The ACSR provides special biospecimen collections and prepares speciality items, e.g., tissue microarrays (TMA), DNA libraries. Requests have been greatest for Kaposi's sarcoma (32%) and non Hodgkin's lymphoma (26%). Dispersed requests include 83% tissue (frozen and paraffin embedded), 18% plasma/serum and 9% other. ACSR also provides tissue microarrays of, e.g., Kaposi's sarcoma and non-Hodgkin's lymphoma, for biomarker assays and has developed collaborations with other groups that provide access to additional AIDS-related malignancy specimens. ACSR members and associates have completed 63 podium and poster presentations. Investigators have submitted 125 letters of intent requests. Discoveries using ACSR have been reported in 61 scientific publications in notable journals with an average impact factor of 7. The ACSR promotes the scientific exploration of the relationship between HIV/AIDS and malignancy by participation at national and international scientific meetings, contact with investigators who have productive research in this area and identifying, collecting, preserving, enhancing, and dispersing HIV/AIDS related malignancy specimens to funded, approved researchers at no fee. Scientific discovery has been advanced by this unique biorepository. Investigators are encouraged to browse the ACSR Internet site for materials to enhance their own scientific initiatives. PMID- 17335576 TI - A comparative study of S/MAR prediction tools. AB - BACKGROUND: S/MARs are regions of the DNA that are attached to the nuclear matrix. These regions are known to affect substantially the expression of genes. The computer prediction of S/MARs is a highly significant task which could contribute to our understanding of chromatin organisation in eukaryotic cells, the number and distribution of boundary elements, and the understanding of gene regulation in eukaryotic cells. However, while a number of S/MAR predictors have been proposed, their accuracy has so far not come under scrutiny. RESULTS: We have selected S/MARs with sufficient experimental evidence and used these to evaluate existing methods of S/MAR prediction. Our main results are: 1.) all existing methods have little predictive power, 2.) a simple rule based on AT percentage is generally competitive with other methods, 3.) in practice, the different methods will usually identify different sub-sequences as S/MARs, 4.) more research on the H-Rule would be valuable. CONCLUSION: A new insight is needed to design a method which will predict S/MARs well. Our data, including the control data, has been deposited as additional material and this may help later researchers test new predictors. PMID- 17335577 TI - An unusual cause of granulomatous disease. AB - BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disorder of phagocytic cells caused by an inability to generate active microbicidal oxygen species required kill certain types of fungi and bacteria. This leads to recurrent life-threatening bacterial and fungal infections with tissue granuloma formation. CASE PRESENTATION: We describe a case of X-linked Chronic granulomatous disease (CGD) diagnosed in an 18-year-old male. He initially presented with granulomatous disease mimicking sarcoidosis and was treated with corticosteroids. He subsequently developed Burkholderia cepacia complex pneumonia and further investigation confirmed a diagnosis of CGD. CONCLUSION: Milder phenotypes of CGD are now being recognised. CGD should be considered in patients of any age with granulomatous diseases, especially if there is a history of recurrent or atypical infection. PMID- 17335578 TI - Public-private partnerships to build human capacity in low income countries: findings from the Pfizer program. AB - BACKGROUND: The ability of health organizations in developing countries to expand access to quality services depends in large part on organizational and human capacity. Capacity building includes professional development of staff, as well as efforts to create working environments conducive to high levels of performance. The current study evaluated an approach to public-private partnership where corporate volunteers give technical assistance to improve organizational and staff performance. From 2003 to 2005, the Pfizer Global Health Fellows program sent 72 employees to work with organizations in 19 countries. This evaluation was designed to assess program impact. METHODS: The researchers administered a survey to 60 Fellows and 48 Pfizer Supervisors. In addition, the team conducted over 100 interviews with partner organization staff and other key informants during site visits in Uganda, Kenya, Ghana, South Africa and India, the five countries where 60% of Fellows were placed. RESULTS: Over three-quarters of Fellowships appear to have imparted skills or enhanced operations of NGOs in HIV/AIDS and other health programs. Overall, 79% of Fellows reported meeting all or most technical assistance goals. Partner organization staff reported that the Fellows provided training to clinical and research personnel; strengthened laboratory, pharmacy, financial control, and human resource management systems; and helped expand Partner organization networks. Local staff also reported the Program changed their work habits and attitudes. The evaluation identified problems in defining goals of Fellowships and matching Organizations with Fellows. Capacity building success also appears related to size and sophistication of partner organization. CONCLUSION: Public expectations have grown regarding the role corporations should play in improving health systems in developing countries. Corporate philanthropy programs based on "donations" of personnel can help build the organizational and human capacity of frontline agencies delivering health services. More attention is needed to measure and compare outcomes of international volunteering programs, and to identify appropriate strategies for expansion. PMID- 17335579 TI - Breast metastasis from a renal cell cancer. AB - BACKGROUND: Metastases to the breast from extramammary tumours are uncommon, and metastatic renal cell carcinoma to the breast is extremely rare. We report a metastasis to the breast from a renal primary with the radiological and histopathological features. CASE PRESENTATION: An 81-year-old lady was seen in the breast clinic for a right breast mass after sustaining a fall. Clinical examination and investigations revealed a metastatic cancer from a renal primary. She received surgical treatment only and is under regular follow-up in the oncology clinic. CONCLUSION: The treatment strategy for metastatic breast diseases is based on a proper assessment of such cases by surgeons, radiologists and histopathologists. PMID- 17335580 TI - Open source model for generating RR intervals in atrial fibrillation and beyond. AB - BACKGROUND: Realistic modeling of cardiac inter-beat (RR) intervals is highly desirable for basic research in cardiac electrophysiology, clinical management of heart diseases, and developing signal processing tools for ECG analysis. METHODS: We present an open source computer model that is capable to generate realistic time series of RR intervals in both physiologic and pathologic conditions. Detailed model structure and the software implementation are described. RESULTS: Examples are provided on how to use this model to generate RR intervals in atrial fibrillation with ventricular pacing, normal sinus rhythm with heart rate variability, and typical atrial flutter with atrioventricular block. The extensibility of the model is also discussed. CONCLUSION: The present computer model provides a unified platform wherein various types of ventricular rhythm can be simulated. The availability of this open source model promises to support and stimulate future studies. PMID- 17335581 TI - Association of the diplotype configuration at the N-acetyltransferase 2 gene with adverse events with co-trimoxazole in Japanese patients with systemic lupus erythematosus. AB - Although co-trimoxazole (trimethoprim-sulphamethoxazole) is an effective drug for prophylaxis against and treatment of Pneumocystis pneumonia, patients often experience adverse events with this combination, even at prophylactic doses. With the aim being to achieve individual optimization of co-trimoxazole therapy in patients with systemic lupus erythematosus (SLE), we investigated genetic polymorphisms in the NAT2 gene (which encodes the metabolizing enzyme of sulphamethoxazole). Of 166 patients with SLE, 54 patients who were hospitalized and who received prophylactic doses of co-trimoxazole were included in the cohort study. Adverse events occurred in 18 patients; only two experienced severe adverse events that lead to discontinuation of the drug. These two patients and three additional ones with severe adverse events (from other institutions) were added to form a cohort sample and were analyzed in a case-control study. Genotype was determined using TaqMan methods, and haplotype was inferred using the maximum likelihood method. In the cohort study, adverse events occurred more frequently in those without the NAT2*4 haplotype (5/7 [71.4%]) than in those with at least one NAT2*4 haplotype (13/47 [27.7%]; P = 0.034; relative risk = 2.58, 95% confidence interval = 1.34-4.99). In the case-control study the proportion of patients without NAT2*4 was significantly higher among those with severe adverse events (3/5 [60%]) than those without severe adverse events (6/52 [11.5%]; P = 0.024; odds ratio = 11.5, 95% confidence interval = 1.59-73.39). We conclude that lack of NAT2*4 haplotype is associated with adverse events with co-trimoxazole in Japanese patients with SLE. PMID- 17335582 TI - Primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical features of 21 cases. AB - BACKGROUND: Primary small cell carcinoma (SCC) of the esophagus is a rare and aggressive tumor with poor prognosis. In this study, we report the clinicopathological characteristics of 21 cases of small cell carcinoma of the esophagus treated at the Cancer Center of Sun Yat-Sen University, with particular focus on the histologic and immunohistochemical findings. METHODS: Twenty-one patient records were reviewed including presenting symptoms, demographics, disease stage, treatment, and follow-up. Histologic features were observed and immunohistochemical detection of cytokeratin (CK), epithelial membrane antigen (EMA), neuron specific enolase (NSE), synaptophysin (Syn), chromogranin A (CgA), neuronal cell adhesion molecules (CD56), thyroid transcriptional factor-1 (TTF-1) and S100 protein (S100) was performed. RESULTS: The median age of patients in the study was 56 years, with a male-to-female ratio of 3.2:1. Histologically, there were 19 "homogenous" SCC esophageal samples and 2 samples comprised of SCC and well-differentiated squamous cell carcinoma. The percentages of SCC samples with positive immunoreactivity were Syn 95.2%, CD56 76.2%, TTF-1 71.4%, NSE 61.9%, CgA 61.9%, CK 57.1%, EMA 61.9%, and S100 19.0%, respectively. The median patient survival time was 18.3 months after diagnosis. The 2-year survival rate was 28.6%. CONCLUSION: Our study suggests that esophageal SCC has similar histology to SCC that arises in the lung compartment, and Chinese patients have a poor prognosis. Higher proportion of positive labeling of Syn, CD56, CgA, NSE, and TTF 1 in esophageal SCC implicate that they are valuably applied in differential diagnosis of the malignancy. PMID- 17335583 TI - Kappa-alpha plot derived structural alphabet and BLOSUM-like substitution matrix for rapid search of protein structure database. AB - We present a novel protein structure database search tool, 3D-BLAST, that is useful for analyzing novel structures and can return a ranked list of alignments. This tool has the features of BLAST (for example, robust statistical basis, and effective and reliable search capabilities) and employs a kappa-alpha (kappa, alpha) plot derived structural alphabet and a new substitution matrix. 3D-BLAST searches more than 12,000 protein structures in 1.2 s and yields good results in zones with low sequence similarity. PMID- 17335584 TI - Urban health insurance reform and coverage in China using data from National Health Services Surveys in 1998 and 2003. AB - BACKGROUND: In 1997 there was a major reform of the government run urban health insurance system in China. The principal aims of the reform were to widen coverage of health insurance for the urban employed and contain medical costs. Following this reform there has been a transition from the dual system of the Government Insurance Scheme (GIS) and Labour Insurance Scheme (LIS) to the new Urban Employee Basic Health Insurance Scheme (BHIS). METHODS: This paper uses data from the National Health Services Surveys of 1998 and 2003 to examine the impact of the reform on population coverage. Particular attention is paid to coverage in terms of gender, age, employment status, and income levels. Following a description of the data between the two years, the paper will discuss the relationship between the insurance reform and the growing inequities in population coverage. RESULTS: An examination of the data reveals a number of key points: a) The overall coverage of the newly established scheme has decreased from 1998 to 2003. b) The proportion of the urban population without any type of health insurance arrangement remained almost the same between 1998 and 2003 in spite of the aim of the 1997 reform to increase the population coverage. c) Higher levels of participation in mainstream insurance schemes (i.e. GIS-LIS and BHIS) were identified among older age groups, males and high income groups. In some cases, the inequities in the system are increasing. d) There has been an increase in coverage of the urban population by non-mainstream health insurance schemes, including non-commercial and commercial ones. The paper discusses three important issues in relation to urban insurance coverage: institutional diversity in the forms of insurance, labour force policy and the non-mainstream forms of commercial and non-commercial forms of insurance. CONCLUSION: The paper concludes that the huge economic development and expansion has not resulted in a reduced disparity in health insurance coverage, and that limited cross-group subsidy and regional inequality is possible. Unless effective measures are taken, vulnerable groups such as women, low income groups, employees based on short-term contracts and rural-urban migrant workers may well be left out of sharing the social and economic development. PMID- 17335585 TI - Estradiol valerate and alcohol intake: dose-response assessments. AB - BACKGROUND: An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from .001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies. RESULTS: With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake. CONCLUSION: The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries. PMID- 17335586 TI - Comparison of outcomes of percutaneous coronary intervention on proximal versus non-proximal left anterior descending coronary artery, proximal left circumflex, and proximal right coronary artery: a cross-sectional study. AB - BACKGROUND: Previous studies have shown that lesions in proximal left anterior descending coronary artery (LAD) may develop more restenosis after balloon angioplasty than lesions in other coronary segments. However, stenting seems to have reduced this gap. In this study, we compared outcomes of percutaneous coronary intervention (PCI) on proximal LAD versus proximal left circumflex (LCX) or right coronary artery (RCA) and proximal versus non-proximal LAD. METHODS: From 1737 patients undergoing PCI between March 2004 and 2005, those with cardiogenic shock, primary PCI, total occlusions, and multivessel or multi-lesion PCI were excluded. Baseline characteristics and in-hospital outcomes were compared in 408 patients with PCI on proximal LAD versus 133 patients with PCI on proximal LCX/RCA (study I) and 244 patients with PCI on non-proximal LAD (study II). From our study populations, 449 patients in study I and 549 patients in study II participated in complete follow-up programs, and long-term PCI outcomes were compared within these groups. The statistical methods included Chi-square or Fisher's exact test, student's t-test, stratification methods, multivariate logistic regression and Cox proportional hazards model. RESULTS: In the proximal LAD vs. proximal LCX/RCA groups, smoking and multivessel disease were less frequent and drug-eluting stents were used more often (p = 0.01, p < 0.001, and p < 0.001, respectively). Patients had longer and smaller-diameter stents (p = 0.009, p < 0.001, respectively). In the proximal vs. non-proximal LAD groups, multivessel disease was less frequent (p = 0.05). Patients had larger reference vessel diameters (p < 0.001) and were more frequently treated with stents, especially direct stenting technique (p < 0.001). Angiographic success rate was higher in the proximal LAD versus proximal LCX/RCA and non-proximal LAD groups (p = 0.004 and p = 0.05, respectively). In long-term follow-up, major adverse cardiac events showed no difference. After statistical adjustment for significant demographic, angiographic or procedural characteristics, long-term PCI outcomes were still similar in the proximal LAD versus proximal LCX/RCA and non-proximal LAD groups. CONCLUSION: Despite the known worse prognosis of proximal LAD lesions, in the era of stenting, our long-term outcomes were similar in patients with PCI on proximal LAD versus proximal LCX/RCA and non-proximal LAD. Furthermore, we had better angiographic success rates in patients with PCI on proximal LAD. PMID- 17335587 TI - Smoking, cessation and expenditure in low income Chinese: cross sectional survey. AB - BACKGROUND: This study was carried-out to explore smoking behaviour and smoking expenditure among low income workers in Eastern China to inform tobacco control policy. METHODS: A self-completion questionnaire was administered to 1958 urban workers, 1909 rural workers and 3248 migrant workers in Zhejiang Province, Eastern China in 2004. RESULTS: Overall 54% of the men and 1.8% of all women were current smokers (at least 1 cigarette per day). Smoking was least common in migrant men (51%), compared with 58% of urban workers and 64% rural inhabitants (P < 0.0001). Forty-nine percent of rural males smoke more than 10 cigarettes/day, and 22% over 20/day. The prevalence of smoking increased with age. Overall 9% of the males had successfully quit smoking. Reasons for quitting were to prevent future illness (58%), current illness (31%), family pressures (20%) and financial considerations (20%). Thirteen percent of current smokers had ever tried to quit (cessation for at least one week) while 22% intended to quit, with migrants most likely to intend to quit. Almost all (96%) were aware that smoking was harmful to health, though only 25% were aware of the dangers of passive smoking. A mean of 11% of personal monthly income is spent on smoking rising to a mean of 15.4% in rural smokers. This expenditure was found to have major opportunity costs, including in terms of healthcare access. CONCLUSION: The prevalence of smoking and successful quitting suggest that smoking prevalence in low income groups in Eastern China may have peaked. Tobacco control should focus on support for quitters, on workplace/public place smoking restrictions and should develop specific programmes in rural areas. Health education messages should emphasise the opportunity costs of smoking and the dangers of passive smoking. PMID- 17335588 TI - Visualization of three-way comparisons of omics data. AB - BACKGROUND: Density plot visualizations (also referred to as heat maps or color maps) are widely used in different fields including large-scale omics studies in biological sciences. However, the current color-codings limit the visualizations to single datasets or pairwise comparisons. RESULTS: We propose a color-coding approach for the representation of three-way comparisons. The approach is based on the HSB (hue, saturation, brightness) color model. The three compared values are assigned specific hue values from the circular hue range (e.g. red, green, and blue). The hue value representing the three-way comparison is calculated according to the distribution of three compared values. If two of the values are identical and one is different, the resulting hue is set to the characteristic hue of the differing value. If all three compared values are different, the resulting hue is selected from a color gradient running between the hues of the two most distant values (as measured by the absolute value of their difference) according to the relative position of the third value between the two. The saturation of the color representing the three-way comparison reflects the amplitude (or extent) of the numerical difference between the two most distant values according to a scale of interest. The brightness is set to a maximum value by default but can be used to encode additional information about the three-way comparison. CONCLUSION: We propose a novel color-coding approach for intuitive visualization of three-way comparisons of omics data. PMID- 17335589 TI - Investigating the cost-effectiveness of videotelephone based support for newly diagnosed paediatric oncology patients and their families: design of a randomised controlled trial. AB - BACKGROUND: Providing ongoing family centred support is an integral part of childhood cancer care. For families living in regional and remote areas, opportunities to receive specialist support are limited by the availability of health care professionals and accessibility, which is often reduced due to distance, time, cost and transport. The primary aim of this work is to investigate the cost-effectiveness of videotelephony to support regional and remote families returning home for the first time with a child newly diagnosed with cancer METHODS/DESIGN: We will recruit 162 paediatric oncology patients and their families to a single centre randomised controlled trial. Patients from regional and remote areas, classified by Accessibility/Remoteness Index of Australia (ARIA+) greater than 0.2, will be randomised to a videotelephone support intervention or a usual support control group. Metropolitan families (ARIA+ < or = 0.2) will be recruited as an additional usual support control group. Families allocated to the videotelephone support intervention will have access to usual support plus education, communication, counselling and monitoring with specialist multidisciplinary team members via a videotelephone service for a 12-week period following first discharge home. Families in the usual support control group will receive standard care i.e., specialist multidisciplinary team members provide support either face-to-face during inpatient stays, outpatient clinic visits or home visits, or via telephone for families who live far away from the hospital. The primary outcome measure is parental health related quality of life as measured using the Medical Outcome Survey (MOS) Short Form SF-12 measured at baseline, 4 weeks, 8 weeks and 12 weeks. The secondary outcome measures are: parental informational and emotional support; parental perceived stress, parent reported patient quality of life and parent reported sibling quality of life, parental satisfaction with care, cost of providing improved support, health care utilisation and financial burden for families. DISCUSSION: This investigation will establish the feasibility, acceptability and cost effectiveness of using videotelephony to improve the clinical and psychosocial support provided to regional and remote paediatric oncology patients and their families. PMID- 17335590 TI - New probes used for IS1245 and IS1311 restriction fragment length polymorphism of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. hominissuis isolates of human and animal origin in Norway. AB - BACKGROUND: Mycobacterium avium is an environmental mycobacterium that can be divided into the subspecies avium, hominissuis, paratuberculosis and silvaticum. Some M. avium subspecies are opportunistic pathogens for animals and humans. They are ubiquitous in nature and can be isolated from natural sources of water, soil, plants and bedding material. Isolates of M. avium originating from humans (n = 37), pigs (n = 51) and wild birds (n = 10) in Norway were examined by IS1245 and IS1311 RFLP using new and specific probes and for the presence of IS901 and ISMpa1 by PCR. Analysis and generation of a dendrogram were performed with the software BioNumerics. RESULTS: IS1311 RFLP provided clear results that were easy to interpret, while IS1245 RFLP generated more complex patterns with a higher discriminatory power. The combination of the two methods gave additional discrimination between isolates. All avian isolates except one were M. avium subsp. avium with two copies of IS1311 and one copy of IS1245, while the isolates of human and porcine origin belonged to M. avium subsp.hominissuis. The isolates from human patients were distributed randomly among the clusters of porcine isolates. There were few identical isolates. However, one isolate from a human patient was identical to a porcine isolate. Regional differences were detected among the porcine isolates, while there was no clustering of human isolates according to type of clinical symptoms or geographical location of the patient's home addresses. CONCLUSION: The results demonstrate that a wide range of M. avium subsp.hominissuis are present in pigs and humans in Norway, and that some of these isolates are very similar. It remains to be determined whether humans are infected from pigs or if they are infected from common environmental sources. PMID- 17335592 TI - Energy sources for laparoscopic partial nephrectomy--critical appraisal. AB - Laparoscopic partial nephrectomy (LPN) has emerged as a viable alternative for the conventional open nephron-sparing surgery (NSS). So far, an adequate renal parenchymal cutting and hemostasis, as well as caliceal repair remains technically challenging. Numerous investigators have developed techniques using different energy sources to simplify the technically demanding LPN. Herein we review these energy sources, discussing perceived advantages and disadvantages of each technique. PMID- 17335593 TI - Epigenetic targets in the diagnosis and treatment of prostate cancer. AB - Prostate cancer (PC) is one of leading cause of cancer related deaths in men. Various aspects of cancer epigenetics are rapidly evolving and the role of 2 major epigenetic changes including DNA methylation and histone modifications in prostate cancer is being studied widely. The epigenetic changes are early event in the cancer development and are reversible. Novel epigenetic markers are being studied, which have the potential as sensitive diagnostic and prognostic marker. Variety of drugs targeting epigenetic changes are being studied, which can be effective individually or in combination with other conventional drugs in PC treatment. In this review, we discuss epigenetic changes associated with PC and their potential diagnostic and therapeutic applications including future areas of research. PMID- 17335594 TI - Percutaneous nephrolithotomy with and without retrograde pyelography: a randomized clinical trial. AB - OBJECTIVE: Since the introduction of percutaneous nephrolithotomy (PCNL), many changes have been added regarding the entrance to pyelocalyceal system such as insertion of the needle pointed to an opaque stone as a guided landmark. We aim at comparing the outcomes of managing renal calculi with and without retrograde pyelography. MATERIALS AND METHODS: In a randomized clinical trial, 55 cases with opaque renal calculi candidates for PCNL with stone in one calyce, in the pelvis or both in one calyce and the pelvis simultaneously were included in a nine-month study. They were randomized into 2 groups, noncatheterized (n = 28) and catheterized (n = 27), called intervention and control groups, respectively. RESULTS: The 2 groups had similar distributions regarding gender, age, duration of operation, length of hospital stay, past history of any surgical procedures on kidney, and stone size. Outcome (residual stone based on aforementioned management) was evaluated with plain X-ray on the morning following the operation. Postoperative hemoglobin decrease was significantly higher in controls than in the intervention group (p < 0.001) (with no clinical significance). No difference in outcome, postoperative fever, duration of surgery, duration of hospital stay and radiation exposure was observed between the 2 groups. CONCLUSION: Our findings showed no differences in major clinical outcomes between the 2 groups (with and without catheter insertion for retrograde pyelography). PMID- 17335595 TI - Comparison of the clinical and pathologic staging in patients undergoing radical cystectomy for bladder cancer. AB - PURPOSE: Radical cystectomy (RCx) is perhaps the most effective therapeutic approach for patients with muscle-invasive bladder cancer. Unfortunately, clinical staging is imprecise and the degree of understaging remains high. This study retrospectively evaluated patients undergoing RCx with regard to pathologic outcomes and degree of upstaging to better identify features that may lessen clinical understaging. MATERIALS AND METHODS: 141 consecutive patients with urothelial bladder carcinoma who were candidates for RCx with curative intent were retrospectively evaluated. Preoperative clinical and pathological (i.e. TURBT) features were compared to pathological outcomes in the cystectomy specimen. Patients were also evaluated as to whether cystectomy was performed as their primary (n = 91) versus secondary (n = 50) treatment for recurrent/progressive disease. Date of cystectomy ( 5 years prior to study) was also analyzed. RESULTS: Of the 141 patients, 54% were upstaged on operative pathology. The greatest degree of upstaging occurred in those with invasive disease preoperatively (cT2-T3). Twenty-six percent of all patients had node-positive disease, and 75% of cT3 patients were node-positive. Seven of 101 (7%) patients with clinical T2 disease were unresectable at the time of surgery. In the primary (vs. secondary) RCx group, more patients were upstaged (63% vs. 40%), non-organ confined (62% vs. 38%), and LN positive (31% vs. 20%). In the more modern cohort, the degree of upstaging was not improved. CONCLUSIONS: Pathologic findings after RCx often do not correlate with preoperative staging. Over half of patients undergoing cystectomy are upstaged on their operative pathology. An improved understanding of the relative frequency of upstaging in cystectomy patients may have important implications in the decision-making and selection for neoadjuvant and adjuvant therapies for these high-risk populations. PMID- 17335596 TI - Stereological study of collagen and elastic system in the detrusor muscle of bladders from controls and patients with infravesical obstruction. AB - OBJECTIVE: Compare detrusor muscle of normal and patients with infravesical obstruction, quantifying the collagen and elastic system fibers. MATERIALS AND METHODS: We studied samples taken from bladders of 10 patients whose ages ranged from 45 to 75 years (mean = 60 years), who underwent transvesical prostatectomy for treatment of BPH. Control material was composed of 10 vesical specimens, removed during autopsies performed in cadavers of accident victims, with ages between 18 and 35 years (mean = 26 years). RESULTS: The results of collagen and elastic fibers quantification (volumetric density) demonstrated the following results in percentage (mean +/- standard deviation): collagen in BPH patients = 4.89 +/- 2.64 and 2.32 +/- 1.25 in controls (p < 0.0001), elastin in BPH patients = 10.63% +/- 2.00 and 8.94% +/- 1.19 in controls (p < 0.0001). CONCLUSION: We found that the components of connective tissue, collagen and elastic system fibers are increased in the detrusor muscle of patients with infravesical obstruction, when compared to controls. PMID- 17335597 TI - Antibiotic resistance and trend of urinary pathogens in general outpatients from a major urban city. AB - OBJECTIVE: We assessed the antimicrobial resistance patterns of pathogens responsible for urinary tract infections (UTI) in outpatients in Sao Paulo, Brazil, as well as the Escherichia coli antimicrobial resistance trend. MATERIALS AND METHODS: Outpatients urine cultures were collected from January 2000 to December 2003. Statistical analysis considered positive results for one bacterial species with colony count >or= 100,000 CFU/mL. Stratification was done on age group and gender. Statistical tests used included chi-square and the chi-square test for trend to evaluate differences between susceptibility rates among age groups and ordering in the E. coli resistance rates per year, respectively. RESULTS: There were 37,261 positive results with Enterobacteriaceae isolated in 32,530 (87.3%) and Gram-positive cocci in 2,570 (6.9%) cultures. E. coli had the highest prevalence (71.6%). Susceptibility tests were performed in 31,716 cultures. E. coli had elevated resistance rates (> 30%) to ampicillin, trimethoprim-sulfamethoxazole, and tetracycline. Significant differences between age groups and ordering among years were observed. CONCLUSIONS: The use of trimethoprim-sulfamethoxazole is precluded in the population studied due to elevated resistance rates (> 30%) among most prevalent pathogens. Significant resistance rate differences among age groups and years were observed, particularly for fluoroquinolones. Fluoroquinolones should be used with caution. Nitrofurantoin should be used as empirical therapy for primary, non-complicated urinary tract infections. PMID- 17335598 TI - Wet heat exposure: a potentially reversible cause of low semen quality in infertile men. AB - OBJECTIVE: To evaluate the recovery of semen quality in a cohort of infertile men after known hyperthermic exposure to hot tubs, hot baths or whirlpool baths. MATERIALS AND METHODS: A consecutive cohort of infertile men had a history remarkable for wet heat exposure in the forms of hot tubs, Jacuzzi or hot baths. Clinical characteristics and exposure parameters were assessed before exposure was discontinued, and semen parameters analyzed before and after discontinuation of hyperthermic exposure. A significant seminal response to withdrawal of hyperthermia was defined as >or= 200% increase in the total motile sperm count (TMC = volume x concentration x motile fraction) during follow-up after cessation of wet heat exposure. RESULTS: Eleven infertile men (mean age 36.5 years, range 31-44) exposed to hyperthermia were evaluated pre and post-exposure. Five patients (45%) responded favorably to cessation of heat exposure and had a mean increase in total motile sperm counts of 491%. This increase was largely the result of a statistically significant increase in sperm motility from a mean of 12% at baseline to 34% post-intervention (p = 0.02). Among non-responders, a smoking history revealed a mean of 5.6 pack-years, compared to 0.11 pack-years among responders. The prevalence of varicoceles was similar in both cohorts. CONCLUSIONS: The toxic effect of hyperthermia on semen quality may be reversible in some infertile men. We observed that the seminal response to exposure elimination varies biologically among individuals and can be profound in magnitude. Among non-responders, other risk factors that could explain a lack of response to elimination of hyperthermia should be considered. PMID- 17335599 TI - The isolated gamma probe technique for sentinel node penile carcinoma detection is unreliable. AB - PURPOSE: Penile carcinoma is a common disease in northeast Brazil. This paper shows the results of the use of isolated gamma probe and discusses the incidence of false negative rates. MATERIALS AND METHODS: From July 2000 to September 2003, 27 newly diagnosed penile carcinoma patients (T1, T2, N0) were included in this prospective study. The isolated gamma probe technique uses the sodium phytate technetium as a tracer and inguinal scanning with probe and after identified the lymph node it is removed. Lymphadenectomies were performed for positive inguinal lymph nodes metastasis. RESULTS: There were 27 patients (mean age 59.6). Follow up was 37 months. Patients from country were 72% and illiterate or semi illiterate were 56.7%. The tumors were mostly located in the glans (81.4%). They were T1, 52 % and T2, 48 %. 81.4% of the patients underwent partial penectomy, and 18.6% underwent postectomy and excision with wide margins. In 48% of the patients, the highest radioactive count rate was located on the left side, while in 41% was located on the right side. Only one patient had a positive pathological lymph node metastasis at the moment of the surgery. Additionally 3 patients became inguinal lymph node positive at the follow up. This date yielded a sensibility rate of 25% and a false-negative rate of 42.8%. CONCLUSION: Isolated gamma probe technique for sentinel node penile carcinoma has a very low sensibility and a high false negative rate. Therefore it is highly advisable the addition of others methods such as lymphoscintigraphy, vital blue, ultrasonography and so on. The isolated gamma probe technique for sentinel node penile carcinoma detection is unreliable. PMID- 17335600 TI - Mannitol extravasation during partial nephrectomy leading to forearm compartment syndrome. AB - We present the first known complication of forearm compartment syndrome after mannitol infusion during partial nephrectomy. We stress the importance of excellent intravenous catheter access and constant visual monitoring of the intravenous catheter site during and after mannitol infusion as ways to prevent this complication. Prompt recognition of compartment syndrome with appropriate intervention can prevent long-term sequelae. PMID- 17335601 TI - True hermaphroditism presenting as an inguinal hernia. AB - A 21-year-old patient with cryptorchidism was found to have a left inguinal mass on physical examination. The patient was operated with a diagnosis of bilateral cryptorchidism and left inguinal hernia. Besides bilateral inguinal undescended testicles, female genital organs like fallopian tubes, uterus and ovary were found on the exploration. PMID- 17335602 TI - Bovine pericardium in penile prosthesis reimplantation. AB - We present a case of a patient who underwent a late penile prosthesis implant using bovine pericardium as a complement to the tunica albuginea involved in intense fibrosis that destroyed the corpus cavernosum after an infectious manifestation. The advantages of using bovine pericardium in the substitution of the tunica albuginea are discussed and its first use as a penile prosthesis lining is reported. PMID- 17335603 TI - Painless inter epididymal testicular torsion of the spermatic cord. AB - Inter epididymal testicular torsion of the spermatic cord is extremely rare and usually diagnosed at surgery. We present an unusual case of spermatic cord torsion in a 14-year-old male patient. It is important to highlight that the torsion occurred only on the distal half of the epididymis leaving the head untwisted and edematous. In addition, the fact that this condition was painless made this case extremely rare and motivated our presentation. PMID- 17335604 TI - Increased urinary N-acetyl-beta-D-glucosaminidase activity in children with hydronephrosis. AB - OBJECTIVE: Hydronephrosis leads to deterioration of renal function. As urinary N acetyl-beta-D-glucosaminidase (U-NAG) activity is considered a sensitive marker of renal tubular impairment, our aim was to measure U-NAG in children with hydronephrosis and to look for a relationship among selected clinical parameters. MATERIALS AND METHODS: We studied 31 children (22 boys and 9 girls, mean age 2.3 +/- 2.5 years) with hydronephrosis grade 1-4 that had U-NAG/creatinine ratio (U NAG/Cr) measured. RESULTS: The U-NAG/Cr was significantly higher in patients with hydronephrosis compared to reference data (p = 0.002). There was no difference in U-NAG/Cr between children with unilateral and bilateral hydronephrosis (p = 0.51). There was no significant difference in U-NAG/Cr between children with grades 1-3 (pooled data) and grade 4, respectively (p = 0.89). There was no correlation between U-NAG/Cr and the grade of hydronephrosis (r = 0.01). CONCLUSIONS: U-NAG/Cr is increased in children with hydronephrosis grade 1-4, and there is no relationship with the grade of hydronephrosis. U-NAG is a useful marker of renal tubular dysfunction, however its relationship with the degree of kidney damage in patients with hydronephrosis should be considered as doubtful. PMID- 17335605 TI - Laparoscopic upper-pole nephroureterectomy in infants. AB - OBJECTIVE: Report the results of laparoscopic upper-pole nephroureterectomy in infants. MATERIALS AND METHODS: Six consecutive infants underwent 7 laparoscopic upper-pole nephroureterectomy. Pre and postoperative evaluation included renal sonography, voiding cystourethrogram and renal scintigraphy. All infants showed upper-pole exclusion. Surgery was performed through a transperitoneal approach with full flank position in all infants. Three or 4 ports were used according to the necessity of retracting the liver. The distal ureter was ligated close to the bladder whenever reflux was present and the dysplastic upper-pole was divided with the help of an electrocautery. Data regarding operative time, postoperative use of analgesics, time to resume oral feeding, hospital stay and tubular function were collected and analyzed. RESULTS: All procedures were concluded as planned. Mean operative time was 135 min. One patient underwent staged bilateral upper-pole nephrectomy. There were no complications and the postoperative hospital stay was 48 hours in 5 procedures and 24 hours in 2 procedures. Pain medication was required only in the first day. Renal tubular function showed improvement in half of the cases. CONCLUSION: Laparoscopic partial nephrectomy is a safe and feasible procedure in infants. Due to the magnification provided by the lenses, a better vision of the structures is achieved, facilitating selective dissection of vascular upper-pole, renal parenchyma and distal ureter. This approach is less damaging to the lower pole, and is associated to low morbidity and a short hospital stay. PMID- 17335606 TI - Total laparoscopic gastrocystoplasty: experimental technique in a porcine model. AB - OBJECTIVE: Describe a unique simplified experimental technique for total laparoscopic gastrocystoplasty in a porcine model. MATERIAL AND METHODS: We performed laparoscopic gastrocystoplasty on 10 animals. The gastroepiploic arch was identified and carefully mobilized from its origin at the pylorus to the beginning of the previously demarcated gastric wedge. The gastric segment was resected with sharp dissection. Both gastric suturing and gastrovesical anastomosis were performed with absorbable running sutures. The complete procedure and stages of gastric dissection, gastric closure, and gastrovesical anastomosis were separately timed for each laparoscopic gastrocystoplasty. The end-result of the gastric suturing and the bladder augmentation were evaluated by fluoroscopy or endoscopy. RESULTS: Mean total operative time was 5.2 (range 3.5 - 8) hours: 84.5 (range 62 - 110) minutes for the gastric dissection, 56 (range 28 80) minutes for the gastric suturing, and 170.6 (range 70 to 200) minutes for the gastrovesical anastomosis. A cystogram showed a small leakage from the vesical anastomosis in the first two cases. No extravasation from gastric closure was observed in the postoperative gastrogram. CONCLUSIONS: Total laparoscopic gastrocystoplasty is a feasible but complex procedure that currently has limited clinical application. With the increasing use of laparoscopy in reconstructive surgery of the lower urinary tract, gastrocystoplasty may become an attractive option because of its potential advantages over techniques using small and large bowel segments. PMID- 17335607 TI - Re: Laparoscopic-assisted nephroureterectomy after radical cystectomy for transitional cell carcinoma. PMID- 17335629 TI - Outbreak with multi-resistant Salmonella Typhimurium DT104 linked to carpaccio, Denmark, 2005. AB - We report an outbreak with Salmonella Typhimurium DT104 resistant to six different antibiotic classes. The outbreak occurred in Denmark in July/August 2005 and was traced to a single restaurant. In addition to patient interviews, an important tool in the investigation of this outbreak was comparison by multi locus variable number of tandem repeat analysis (MLVA) typing of patient strains with strains from the food surveillance system. This showed that the source of the outbreak was imported beef served as carpaccio. Carpaccio, thinly sliced raw fillet of beef, has not previously been associated with outbreaks, but should be considered a high-risk food item. This outbreak was one of two in different European Union (EU) countries traced back to beef from one company in a third EU country. This underscores the importance of efficient international Salmonella surveillance and food-safety control systems enabling timely interventions within the EU. PMID- 17335630 TI - Increase in bloodstream infections in Finland, 1995-2002. AB - A national, population-based laboratory surveillance of bloodstream infections (BSI) in Finland was performed. Blood-culturing rates were determined from data from clinical microbiology laboratories and trends in rates were evaluated using Poisson regression. During 1995-2002, 51,510 cases of BSI were notified; the annual incidence increased from 104 to 145 cases/100,000 (40%). Rates increased in all age groups but persons aged >or= 75 years accounted for 28% of cases and showed the largest rate increase. Escherichia coli, coagulase-negative staphylococci, Staphylococcus aureus and Streptococcus pneumoniae accounted for 58% of isolates and their relative proportions were unchanged over time. The annual blood-culturing rate increased by one-third during the study period but the number of BSI detected per blood cultures remained unchanged. Regional BSI incidence was significantly associated with blood-culturing rates. We conclude that the increase in BSI rates may have been due to more frequent blood culturing but was not associated with changes in the reporting system or aetiology of BSI. PMID- 17335631 TI - Exploring the cost effectiveness of an immunization programme for rotavirus gastroenteritis in the United Kingdom. AB - Rotavirus is the most common cause of gastroenteritis in children aged <5 years old, two new vaccines have recently been developed which can prevent associated morbidity and mortality. While apparently safe and efficacious, it is also important to establish whether rotavirus immunization is cost effective. A decision analytical model which employs data from a review of published evidence is used to determine the cost effectiveness of a rotavirus vaccine. The results suggest that some of the health sector costs, and all of the societal costs, of rotavirus gastroenteritis in children can be avoided by an immunization programme. The additional cost to the health sector may be considered worthwhile if there is a sufficient improvement in the quality-of-life of children and parents affected by gastroenteritis; this study did not find any evidence of research which has measured the utility gains from vaccination. PMID- 17335632 TI - The use of clinical profiles in the investigation of foodborne outbreaks in restaurants: United States, 1982-1997. AB - Improving the efficiency of outbreak investigation in restaurants is critical to reducing outbreak-associated illness and improving prevention strategies. Because clinical characteristics of outbreaks are usually available before results of laboratory testing, we examined their use for determining contributing factors in outbreaks caused by restaurants. All confirmed foodborne outbreaks reported to the Centers for Disease Control and Prevention (CDC) from 1982 to 1997 were reviewed. Clinical profiles were developed based on outbreak characteristics. We compared the percentage of contributing factors by known agent and clinical profile to their occurrence in outbreaks of unclassified aetiology. In total, 2246 foodborne outbreaks were included: 697 (31%) with known aetiology and 1549 (69%) with aetiology undetermined. Salmonella accounted for 65% of outbreaks with a known aetiology. Norovirus-like clinical profiles were noted in 54% of outbreaks with undetermined aetiology. Improper holding times and temperatures were associated with outbreaks caused by Clostridium perfringens, Bacillus cereus, Staphylococcus aureus, and Salmonella, and also with outbreaks of undetermined aetiology that fitted diarrhoea-toxin and vomiting-toxin clinical profiles. Poor personal hygiene was associated with norovirus, Shigella, and Salmonella, and also with outbreaks that fitted norovirus-like and vomiting-toxin clinical profiles. Contributing factors were similar for outbreaks with known aetiology and for those where aetiology was assigned by corresponding clinical profile. Rapidly categorizing outbreaks by clinical profile, before results of laboratory testing are available, can help identification of factors which contributed to the occurrence of the outbreak and will promote timely and efficient outbreak investigations. PMID- 17335634 TI - The effect of discontinued use of antimicrobial growth promoters on the risk of therapeutic antibiotic treatment in Danish farrow-to-finish pig farms. AB - This study estimated the effect of discontinued use of antimicrobial growth promoters (duAGPs) on the risk of antibiotic treatment for diarrhoea, arthritis, pneumonia, unthriving and miscellaneous disorders in Danish pig farms. The estimation was done in a case-crossover study comparing: (1) the proportion of days per farm where treatment was performed (PDT) and (2) the proportion of pigs treated per day per farm at days where treatment was performed (PPT) before and after duAGPs at 68 farrow-to-finish farms. The farms were selected using a two stage (veterinarian/farm) convenience sampling. On average, during the first year after duAGPs there was a significant increase in the risk of antibiotic treatment for diarrhoea (PDT: OR 2.5, 95% CI 1.7-3.8; PPT: OR 1.6, 95% CI 1.1-2.2). However, the effect varied among farms--some farms experienced substantial problems, while others experienced few problems after duAGPs. No effect was identified for the risk of treatment for other diseases. PMID- 17335633 TI - Clinical surveillance of thrombotic microangiopathies in Scotland, 2003-2005. AB - The prevalence, incidence and outcomes of haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP) are not well established in adults or children from prospective studies. We sought to identify both outcomes and current management strategies using prospective, national surveillance of HUS and TTP, from 2003 to 2005 inclusive. We also investigated the links between these disorders and factors implicated in the aetiology of HUS and TTP including infections, chemotherapy, and immunosuppression. Most cases of HUS were caused by verocytotoxin-producing Escherichia coli (VTEC), of which serotype O157 predominated, although other serotypes were identified. The list of predisposing factors for TTP was more varied although use of immunosuppressive agents and severe sepsis, were the most frequent precipitants. The study demonstrates that while differentiating between HUS and TTP is sometimes difficult, in most cases the two syndromes have quite different predisposing factors and clinical parameters, enabling clinical and epidemiological profiling for these disorders. PMID- 17335635 TI - Do characteristics of patients with major depressive disorder differ between primary and psychiatric care? AB - BACKGROUND: Despite the need for rational allocation of resources and cooperation between different treatment settings, clinical differences in patients with major depressive disorder (MDD) between primary and psychiatric care remain obscure. We investigated these differences in representative patient populations from primary care versus secondary level psychiatric care in the city of Vantaa, Finland. METHOD: We compared MDD patients from primary care in the Vantaa Primary Care Depression Study (PC-VDS) (n=79) with psychiatric out-patients (n=223) and in patients (n=46) in the Vantaa Depression Study (VDS). DSM-IV diagnoses were assigned by the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I in PC-VDS) or Schedules for Clinical Assessment in Neuropsychiatry (SCAN in VDS), and SCID-II interviews. Comparable information was collected on depression severity, Axis I and II co-morbidity, suicidal behaviour, preceding clinical course, and attitudes towards and pathways to treatment. RESULTS: Prevalence of psychotic subtype and severity of depression were highest among in-patients, but otherwise few clinical differences between psychiatric and primary care patients were detected. Suicide attempts, alcohol dependence, and cluster A personality disorder were associated with treatment in psychiatric care, whereas cluster B personality disorder was associated with primary care treatment. Patients' choice of the initial point of contact for current depressive symptoms seemed to be independent of prior clinical history or attitude towards treatment. CONCLUSIONS: Severe, suicidal and psychotic depression cluster in psychiatric in-patient settings, as expected. However, MDD patients in primary care or psychiatric out patient settings may not differ markedly in their clinical characteristics. This apparent blurring of boundaries between treatment settings calls for enhanced cooperation between settings, and clearer and more structured division of labour. PMID- 17335636 TI - Orbitofrontal cortex volume in late life depression: influence of hyperintense lesions and genetic polymorphisms. AB - BACKGROUND: Orbitofrontal cortex (OFC) volumetric differences have been reported in depression, but in relatively small samples. Factors associated with these differences are not well described. We examined OFC volumes in a large sample of elderly depressed and non-depressed subjects, exploring the relationship between OFC volume, 5HTTLPR genotype, apolipoprotein E (APOE) genotype and hyperintense lesion volume. We hypothesized that smaller OFC volume would be associated with depression, greater hyperintense lesion volume and severity, and APOE epsilon4 or 5HTTLPR short allele carriers. METHOD: A total of 226 depressed and 144 non depressed older subjects completed 1.5 T magnetic resonance imaging (MRI) and genotyping. OFC volumes and lesion volumes were measured using standardized methods. Lesion severity was additionally rated using the Coffey rating scale. Differences between groups were compared while controlling for age, sex and total cerebral volume; separate models added lesion measures and genetic polymorphisms. RESULTS: Depressed subjects exhibited smaller OFC volumes. There was a trend for a negative association between white-matter lesion volume and OFC volume; however, rated white-matter lesion severity was significantly negatively associated with OFC volume. There was no association between gray-matter lesion measures or 5HTTLPR genotype and OFC volume. Contrary to our hypothesis, subjects who were APOE epsilon4 allele positive exhibited larger OFC volumes; in secondary analyses, this finding was limited to the non-depressed group. CONCLUSIONS: Reduced OFC volumes are seen in depression and associated with greater severity of white-matter lesions. Healthy subjects who are APOE epsilon4 allele positive exhibited larger OFC volumes. This finding should be examined in other populations. PMID- 17335637 TI - The epidemiology of DSM-IV specific phobia in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions. AB - BACKGROUND: There is a lack of current detailed national data on the prevalence, correlates, disability and co-morbidity of DSM-IV specific phobia (SP), the prevalence of specific objects and situations feared, and associations between impairment, treatment and co-morbidity and the number of specific situations and objects feared, among adults in the USA. METHOD: The data were derived from a large (43093) representative sample of the adult population in the USA. RESULTS: Prevalences of 12-month and lifetime DSM-IV SP were 7.1% and 9.4% respectively. Being female, young, and low income increased risk, while being Asian or Hispanic decreased risk (p<0.05). The mean age at onset of SP was 9.7 years, the mean duration of episode was 20.1 years and only 8.0% reported treatment specifically for SP. Most specific phobias involved multiple fears, and an increasing number of fears, regardless of content, was associated with greater disability and impairment, treatment seeking and co-morbidity with other Axis I and II disorders. CONCLUSIONS: SP is a highly prevalent, disabling and co-morbid disorder in the US adult population. The early onset of SP and the disorders most strongly associated with it highlights the need for longitudinal studies beginning in early childhood. Results suggest the existence of a generalized subtype of SP much like social phobia, which, once revealed, may lead to a classification of SP that is more etiologically and therapeutically meaningful. PMID- 17335638 TI - Implications for neurobiological research of cognitive models of psychosis: a theoretical paper. AB - BACKGROUND: Cognitive models of the positive symptoms of psychosis specify the cognitive, social and emotional processes hypothesized to contribute to their occurrence and persistence, and propose that vulnerable individuals make characteristic appraisals that result in specific positive symptoms. METHOD: We describe cognitive models of positive psychotic symptoms and use this as the basis of discussing recent relevant empirical investigations and reviews that integrate cognitive approaches into neurobiological frameworks. RESULTS: Evidence increasingly supports a number of the hypotheses proposed by cognitive models. These are that: psychosis is on a continuum; specific cognitive processes are risk factors for the transition from subclinical experiences to clinical disorder; social adversity and trauma are associated with psychosis and with negative emotional processes; and these emotional processes contribute to the occurrence and persistence of psychotic symptoms. There is also evidence that reasoning biases contribute to the occurrence of delusions. CONCLUSIONS: The benefits of incorporating cognitive processes into neurobiological research include more sophisticated, bidirectional and interactive causal models, the amplification of phenotypes in neurobiological investigations by including emotional processes, and the adoption of more specific clinical phenotypes. For example, there is potential value in studying gene x environment x cognition/emotion interactions. Cognitive models and their derived phenotypes constitute the missing link in the chain between genetic or acquired biological vulnerability, the social environment and the expression of individual positive symptoms. PMID- 17335639 TI - Remission and relapse after the first hospital admission in psychotic depression: a 4-year naturalistic follow-up. AB - BACKGROUND: Few studies have examined the course of illness among severely depressed patients ascertained at first hospitalization. Using data from the Suffolk County Mental Health Project (SCMHP), we investigated the times to and predictors of the first full remission and the first relapse during a 4-year period in a first-admission cohort with major depressive disorder (MDD) with psychotic features. METHOD: The cohort included 87 county-wide, first-admission patients with a longitudinal consensus diagnosis of MDD with psychotic features who were systematically followed over a 4-year period. We examined the associations of background, clinical and treatment factors, and time-varying indices of antidepressant (AD) and antipsychotic (AP) medication use to time to remission and relapse using Cox regression. RESULTS: By the 4-year follow-up, 60 respondents (69.0%) had achieved a period of full remission (median time of 22 weeks among remitters and 54 weeks in the full sample). In the multivariable analysis, longer time to remission was associated with longer latency between initial episode and hospitalization, lower pre-hospital Global Assessment of Functioning (GAF) score, and lack of insurance, but not use of medication. Twenty six remitters (43.3%) relapsed (median time of 50 weeks among those who relapsed and 192 weeks among all remitters). None of the risk factors or time-varying medication variables was significantly associated with time to relapse. CONCLUSION: Only two-thirds of the sample had at least one full remission by 4 years, and almost half of them subsequently relapsed. Poorer pre-hospital resources predicted remission but not relapse. Medication use over the follow-up was not associated with remission or relapse. PMID- 17335640 TI - Puberty moderates genetic influences on disordered eating. AB - BACKGROUND: Previous research suggests that genetic influences on disordered eating may be greater in pubertal than pre-pubertal girls. Although these findings are consistent with pubertal activation of genetic influences on disordered eating, earlier studies were unable to directly test this hypothesis. The purpose of the present study therefore was to directly examine this possibility by investigating whether pubertal development moderates genetic influences on disordered eating. METHOD: Participants were 510 female adolescent twins from the Minnesota Twin Family Study. Disordered eating was measured with the Total Score of the Minnesota Eating Behavior Survey, while pubertal status was assessed with the Pubertal Development Scale. RESULTS: Consistent with our hypothesis, model-fitting indicated significant increases in genetic influence on disordered eating with advancing pubertal development. CONCLUSIONS: These findings suggest that puberty influences the expression of genes for disordered eating. PMID- 17335641 TI - Biological markers of intellectual disability in tuberous sclerosis. AB - BACKGROUND: Intellectual disability (ID) is highly prevalent in tuberous sclerosis (TS). Putative neurobiological risk factors include indices of cortical tuber (CT) load and epilepsy. We have used univariate and multivariate analyses, including both CT and epilepsy measures as predictors, in an attempt to clarify the pattern of cross-sectional associations between these variables and ID in TS. METHOD: Forty-eight children, adolescents and young adults with TS were identified through regional specialist clinics. All subjects underwent thorough history taking and examination, and had brain magnetic resonance imaging (MRI) scans. The number and regional distribution of CTs was recorded. Subjects were assigned to one of nine ordered intellectual quotient (IQ) categories (range 130) using age-appropriate tests of intelligence. RESULTS: On univariate analyses, ID was significantly associated with both a history of infantile spasm (IS) (Z= 2.49, p=0.01) and total CT count (Spearman's rho=-0.30, p=0.04). When controlling for total CT count, the presence of CTs in frontal (regression coefficient=-2.43, p=0.02) and temporal (regression coefficient=-1.60, p=0.02) lobes was significantly associated with ID. In multivariate analyses the association between IS and ID was rendered insignificant by the inclusion of the presence of CTs in temporal and frontal lobes, both of which remained associated (p=0.05 and p=0.06 respectively) with ID. CONCLUSIONS: The presence of CTs in specific brain regions as opposed to a history of IS was associated with ID in TS. The significance of these findings is discussed in relation to previous work in TS, and the neural basis of intelligence. PMID- 17335642 TI - The gradual emergence of sex differences in aggression: alternative hypotheses. AB - Nearly a century of observational studies and more recent longitudinal surveys reveal that, in infancy, girls and boys use force at similar rates. Over the next few years boys become significantly more aggressive. Alternative hypotheses accounting for the widening gender gap are evaluated. These include hypotheses about normative patterns of male escalation and female desistance; boys' preference for active play that promotes aggression; girls' tendency to hide aggression; girls' use of alternative forms of aggression; boys' increased risk for the cognitive and emotional problems that are linked to aggression; boys' sensitivity to situational triggers of aggression; and boys' vulnerability to adverse rearing environments. The evidence bearing on each hypothesis is mixed. In general, the overall difference between the sexes appears to be produced by a minority of boys who deploy aggression at high rates. Three general principles govern the emergence of sex differences in aggression: female precocity, male vulnerability, and the salience of sex as a social category that shapes children's lives. PMID- 17335643 TI - Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation. AB - This review focused on the treatment-emergent mania/hypomania (TEM) associated with repetitive transcranial magnetic stimulation (rTMS) treatment of depression. English-language literature published from 1966-2006 and indexed in Medline was searched. Ten of 53 randomized controlled trials on rTMS treatment of depression specifically addressed TEM. The pooled TEM rate is 0.84% for the active treatment group and 0.73% for the sham group. The difference is not statistically significant. Along with case reports, a total of 13 cases of TEM associated with rTMS treatment of depression have been published. Most of these patients were diagnosed with bipolar disorder and the majority of patients experiencing TEM took medication concurrent with rTMS. The parameters of rTMS used in these cases were scattered over the spectrum of major parameters explored in previous studies. Most train durations and intervals were within the published safety guidelines of the field. Reducing the frequency of sessions from two per day to one per day might be associated with a lower likelihood of TEM recurrence. The severity of manic symptoms varied significantly, but all cases responded to treatment that included a decrease or discontinuation of antidepressant and/or rTMS treatment and/or use of anti-manic medication. Current data suggests that rTMS treatment carries a slight risk of TEM that is not statistically higher than that associated with sham treatment. More systematic studies are needed to better understand TEM associated with rTMS. Special precautions and measures should be adopted to prevent, monitor, and manage TEM in research and practice. PMID- 17335644 TI - Effects of naltrexone on cocaine- and sucrose-seeking behaviour in response to associated stimuli in rats. AB - The non-selective opioid receptor antagonist naltrexone reduces cocaine-induced reinstatement of drug-seeking behaviour in abstinent rats. The current study sought to determine whether the opioid system is also involved in cocaine-seeking behaviour induced by cocaine-associated stimuli in abstinent rats. Adult male rats were trained to press a lever either to self-administer cocaine or to obtain sucrose pellets in the presence of distinctive discriminative and conditioned stimuli. After a period of extinction, re-exposure to cocaine-associated cues selectively elicited robust and enduring responding at the active lever; sucrose pellet-associated cues revived seeking behaviour less pronouncedly. Pretreatment with naltrexone (0.25, 1, 2.5 mg/kg s.c., 20 min before reinstatement tests) dose dependently prevented cue-induced cocaine-seeking behaviour, whereas (2.5 mg/kg s.c.) did not affect the degree of cue-induced sucrose-seeking behaviour. These results provide the first evidence that naltrexone influences cocaine seeking induced by conditioned stimuli in abstinent rats; this effect appears selective for cocaine reinstatement as opposed to a non-drug reinforcer. PMID- 17335646 TI - Application and evaluation of non-invasive examination for Budd-Chiari syndrome. PMID- 17335647 TI - Preliminary evaluation of magnetic resonance fresh blood imaging for diagnosis of Budd-Chiari syndrome. AB - BACKGROUND: Budd-Chiari syndrome (BCS) is a rare disease with portal hypertension caused by the blockage of the hepatic vein and/or the inferior vena cava (IVC). Angiography is the "golden standard" for diagnosis, but it is an invasive examination. To assess the diagnostic value of a fresh blood imaging (FBI) relative to BCS, we used a magnetic resonance angiography (MRA) with an FBI sequence for a preoperative evaluation of the BCS patients in this study. METHODS: Fifty patients who were suspected of having BCS after they had been checked by a B-ultrasound were studied. 2D and 3D FBI were performed on a 1.5T superconductive MR scanner. Original images were rebuilt using a maximal intensity projection (MIP) method on the console. Two doctors reviewed all images before they learned of the angiography results. We then compared the diagnoses obtained from the FBI and angiography results to evaluate the diagnostic value of the FBI. RESULTS: Forty-one patients were diagnosed as BCS and 9 as non-BCS based on an angiography. The FBI correctly diagnosed 38 patients, incorrectly diagnosed 1 patient, and missed diagnosis in 3 patients. Thus, the diagnostic sensitivity of the FBI is 93% (38/41), the specificity is 89% (8/9) and the accuracy is 92% (46/50). The FBI images of the 13 membranous stenoses of the IVC showed a sudden stenosis of the post-liver segment of the IVC. The Images of the 5 patients with a membranous obstruction of the IVC showed IVC thickening and an absence of blood signals in the post-hepatic segment of the IVC. The images of the 4 patients with the segmental thrombosis of the IVC showed abnormal and intermittent signals in the IVC. The images of the 6 patients with a simple hepatic vein obstruction showed obstructive hepatic veins. The images of the 6 patients with the stenosis of both the IVC and the hepatic veins showed the stenosis of the IVC, the thickening of the hepatic veins and the formation of a compensatory circulation within the liver. Lastly, the images of the 7 patients showed a combination of the IVC thrombosis with stenosis or with the obstruction of one or two hepatic veins. CONCLUSIONS: An FBI can show a membranous stenosis, and an obstruction and thrombosis of the IVC. In addition, it can also demonstrate the thickening of the flexural hepatic vein and the development of intra-hepatic compensatory branches with slow blood flow. Thus, it can guide the puncturing and opening of the hepatic vein involved in an interventional therapy for BCS patients. PMID- 17335649 TI - Clinical significance of multislice spiral CT scans in hepatic veins occlusion in Budd-Chiari syndrome. AB - BACKGROUND: Budd-Chiari syndrome with hepatic vein occlusion (HVBCS) can induce severe portal hypertension and liver damage. We retrospectively analyzed hepatic CT features of HVBCS and evaluated the usefulness of triphasic enhancement of CT examinations and CT angiography (CTA) in its diagnosis. METHODS: Twenty-five cases with HVBCS, confirmed by digital subtraction angiography (DSA), received a triphasic enhancement CT scan within one week before DSA. The CTA images of the relevant blood vessels were reconstructed with maximum intensity projection, volume rendering and oblique reformat techniques. RESULTS: Compared with DSA, the detection rate of transverse CT and CTA images for abnormal hepatic vein were 81.7% (58/71) and 95.8% (68/71) (chi(2) = 7.044, P = 0.008), for membranous obstruction were 47.4% (9/19) and 84.2% (16/19) respectively (chi(2) = 5.729, P = 0.017), for segmental obstruction were 88.0% (22/25) and 100% (25/25) respectively (chi(2) = 1.418, P = 0.234). The detection rates for hepatic vein stenosis were 100% with each method. Diffuse hepatomegaly was found in all 6 cases in acute phase and 3 of 19 cases in chronic phase who had severe obstruction of three hepatic veins without patent intrahepatic collaterals. The other 16 cases in chronic phase had hepatatrophia to different extents related to the obstructed hepatic vein. All in acute phase and 15 in chronic phase presented typical patchy enhancement initially in caudate lobe and perihilar areas and enlarged with time delay. In all cases, parenchyma areas with atrophy, necrosis and congestion demonstrated lower and later enhancement. In all the parts, which had normal enhancement at least one patent outflow hepatic vein, accessory hepatic vein or collateral vessel was detected. CONCLUSION: Dynamic enhancement CT examination by multislice spiral CT not only could improve the diagnosis of HVBCS by CTA technique, but also could noninvasively provide anatomical information and reveal damage to the hepatic parenchyma. PMID- 17335650 TI - Surgical treatment of 82 patients with diabetic lower limb ischemia by distal arterial bypass. AB - BACKGROUND: Diabetic lower limb ischemia is a serious complication of diabetes mellitus. This study was conducted to investigate the effectiveness of distal arterial bypass treatment in diabetic patients with lower limb ischemia. METHODS: From July 2000 to July 2004, 96 lower limbs of 82 diabetic patients (type 2) with severe lower limb ischemia were treated in Xuan Wu Hospital. Arterial bypass with femoro-popliteal polytetrafluoroethylene (PTFE) and graft-tibial autologous grafts was performed on 31 limbs (32.3%). Popliteal-tibial artery bypass alone was performed on 22 limbs (22.9%). Combined iliac artery stenting, femoro popliteal artery PTFE graft bypass, and graft-tibial artery autologous graft bypass was performed on 12 limbs (12.5%), and femoro-tibial artery graft bypass was performed on 10 limbs (10.4%). Popliteal-tibial-pedal artery graft bypass was performed on 7 limbs (7.3%). RESULTS: Arterial grafts in 92 limbs of 79 patients were patent on discharge. Three patients with 4 ischemic limbs (3.7%) died of respiratory failure 12 hours, 3 days and 7 days after operation respectively. Early operation success rate was 96.3% (79/82). Graft patency rate of patients on discharge was 95.8% (92/96). The short-term total effectiveness rate was 83.3% (80/96). Foot ulcer healing rate was 35.7% (10/28). 97.4% (75/77) patients were followed up for a mean of 13.5 months. The long-term total effective rate was 80.7% (71/88). The total amputation rate was 4.5% (4/88). Mortality was 4.5%. The total graft patency rate was 90.9% (80/88). CONCLUSION: In the treatment of diabetic foot, distal lower limb arterial bypass can help to avoid amputation or lower the amputation level, and may promote foot ulcer healing and improve patient's quality of life. PMID- 17335651 TI - Modified vitrification method for cryopreservation of human ovarian tissues. AB - BACKGROUND: Vitrification is a prospective technology in ovarian tissue cryopreservation, but it is still in an initial stage. This study was conducted to investigate a modified vitrification protocol for human ovarian tissue, which can be used as an alternative to preserve fertility for young women with cancer who have to undergo cytotoxic therapy and sterilization. METHODS: Ovarian tissue samples were collected from 15 patients and randomly allocated to groups of fresh, vitrification, and conventional slow freezing. A modified carrierless vitrification method was applied. The proportion of morphologically intact follicles in fresh ovarian tissues was compared with that in warmed/thawed tissues. The initial growth of the follicles and the concentrations of estradiol and progesterone were detected to determine the viability and endocrine function of the cryopreserved tissues. RESULTS: The proportion of morphologically intact primordial follicles in the fresh group (97.6%) was significantly higher than that in the other two groups (vitrification group 80.3% and slow-freezing group 72.6%, P < 0.001). In both the vitrification and slow-freezing groups, estradiol and progesterone were secreted continuously during 2-week culture in vitro, the proportion of primary follicles were both significantly increased compared to the fresh group. No statistically significant differences existed between the two groups after cryopreservation in the proportion of both primordial and primary follicles, and the concentrations of estradiol and progesterone (P > 0.05). CONCLUSION: The modified vitrification method for cryopreservation of human ovarian tissues is effective, simple, and inexpensive. PMID- 17335652 TI - Clinical and pathological characteristics of primary intraspinal hemangiopericytoma and choice of treatment. AB - BACKGROUND: Primary intraspinal hemangiopericytoma is a rare malignant mesenchymal tumor with high rates of recurrence and metastasis. Surgery is the main therapeutic procedure for this lesion. This clinical research was undertaken to analyze the pathological characteristics, clinical course, and the choice of treatment for this lesion. METHODS: Twenty-three patients with primary intraspinal hemangiopericytomas were treated from 1987 to 2004. The clinical and imaging features, pathological findings, therapeutic procedures, and prognosis were analyzed retrospectively. RESULTS: Primary intraspinal hemangiopericytoma is more likely to attack middle-aged persons. The tumor mainly manifests as muscle weakness and sensor abnormalities. Microscopic examination showed slit-like vascular spaces and oral- or spindle-shaped cells with slightly acidic cytoplasm and oral nuclei. Tumors were subtotally resected in 11 patients, subtotally resected with postoperative radiotherapy in 4, totally resected in 5, and totally resected with postoperative radiotherapy in 3. Two patients were given spinal stabilization after total resection. Recurrence and metastatic rates were 50% and 0 in intradural patients. They were 73% and 27% in extradural patients, respectively. CONCLUSIONS: The tumor should be resected en bloc with the neighboring dural mater to reduce recurrence and metastasis. Patients with subtotal resection need adjuvant radiotherapy. Patients with evident spinal involvement may benefit from spinal stabilization. The prognosis of the lesion arising from the dural mater is better. PMID- 17335653 TI - Effects of caloric vestibular stimulation on serotoninergic system in the media vestibular nuclei of guinea pigs. AB - BACKGROUND: Anatomic and electrophysiological studies have revealed that the neurons located in the media vestibular nuclei (MVN) receive most of the sensory vestibular input coming from the ipsilateral labyrinth and the responses of MVN neurons to caloric stimulation directly reflect changes in primary vestibular afferent activity. The aim of this study was to clarify the intrinsic characteristics of serotonin (5-hydroxytryptamine, 5-HT) release in the MVN during the period of vertigo induced by caloric stimulation. METHODS: We used an in vivo microdialysis technique to examine the effects of caloric stimulation on the serotoninergic system in MVN. Twenty four guinea pigs were randomly divided into the groups of irrigation of the ear canal with hot water (n = 6), ice water (n = 6) and 37 degrees C water (n = 4), and the groups of irrigation of the auricle with hot water (n = 4) and ice water (n = 4), according to different caloric vestibular stimulation. We examined the animal's caloric nystagmus with a two-channel electronystagmographic recorder (ENG), and meanwhile examine serotonin (5-hydroxytryptamine, 5-HT) level in the MVN with microdialysis technique after caloric stimulation. RESULTS: In the caloric test the hot water (44 degrees C) irrigation of the right external auditory canal induced horizontal nystagmus towards the right side lasting about 60 seconds and the ice water irrigation of the right external auditory canal induced it towards the left side lasting for about 90 seconds. No nystagmus was induced by 37 degrees C water irrigation of the external ear canal. Therefore, it was used as a negative control stimulation to the middle ear. The MVN 5-HT levels significantly increased in the first 5-minute collecting interval and increased to 254% and 189% of the control group in the second collecting interval in response to caloric vestibular stimulation with ice water and hot water respectively. The serotonin release was not distinctly changed by the irrigation of the auricle with ice water or hot water. CONCLUSIONS: Neither somato-sensory stimulation of the middle ear nor nonspecific cold or hot stress affects the serotonin release. The rise of 5-HT in MVN may be involved in the mechanism of vertigo induced by caloric stimulation. PMID- 17335654 TI - 18F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer. AB - BACKGROUND: The outcome of surgical treatment of non-small-cell lung cancer (NSCLC) remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. (18)F-fluoro-2-deoxy-glucose ((18)F-FDG) uptake on positron-emission tomography (PET) is associated with the aggressiveness of NSCLC. The present study focused on the role of (18)F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC. METHODS: A retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value (SUV(max)), in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients' recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUV(max) and other factors was also analyzed. RESULTS: Patients with SUV(max) more than 11 had a disease-free survival and overall survival shorter than patients with SUV(max) less than 11 in univariate analyses (P < 0.001, P = 0.002). In the multivariate analysis, SUV(max) (dichotomized by 11) was the only significant predictor for tumor recurrence. TNM stage and SUV(max) (dichotomized by 11) were independent predictors for the overall survival. Associations of SUV(max) with p53 overexpression, proliferating cell nuclear antigen (PCNA) labeling index and microvascular density of the tumor were significant in the entire group. CONCLUSIONS: (18)F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy. PMID- 17335655 TI - Laparoscopic radical cystectomy with ileal neobladder and rectum pouch: the initial experience of 28 cases in China. AB - BACKGROUND: We presented the technique and outcomes of laparoscopic radical cystectomy performed in 28 patients with bladder cancer to evaluate its clinical efficacy and feasibility. METHODS: Among the 28 patients, aged from 58 to 73 years (mean 68.5 years), 26 were transitional cell carcinoma grads II - III and 2 squamous carcinoma. Laparoscopic radical cystectomy plus bladder reconstruction was performed in all cases, among them 15 with ileum, 10 with rectum pouch, and 3 with ureterostomy. The operating time, the blood loss, the intestine function and the complications were observed. RESULTS: All procedures were successful. The operating times were 7 - 10 hours, the blood loss was 400 - 1500 ml (mean 850 ml), the intestine function recovered at 72 hours after operation, and all ureteral catheters were removed at 2 weeks after surgery. The results of intravenous urography were normal at 3-month, 1-year, and 2-year follow-up after surgery. CONCLUSIONS: Laparoscopic radical cystectomy for invasive bladder cancer is safe and efficient, with good operating field, reliable hemostasis, mini invasion, less celiac complications, and rapid recovery. This surgery is worth being extended. PMID- 17335656 TI - Pyogenic liver abscess caused by Klebsiella pneumoniae: analysis of the clinical characteristics and outcomes of 84 patients. AB - BACKGROUND: The increased incidence of pyogenic liver abscess caused by Klebsiella pneumoniae (K.pneumoniae) was reported in the recent literature. This study was conducted retrospectively to investigate the clinical characteristics and outcomes of these patients. METHODS: Microbiological and medical databases of a medical center were searched from January 2000 to June 2003. Eighty-four patients with liver abscess caused by K.pneumoniae were analyzed. RESULTS: In the 84 patients, 52 men and 32 women aged (58.2 +/- 13.3) years on average, 64.4% had concomitant diabetes mellitus and 23.8% had biliary disease. The most common clinical symptoms were fever (98.8%), chills (69.0%) and abdominal pain (58.3%). 85.7% of the 84 patients received catheter drainage for the abscess. The length of hospital stay was (17.4 +/- 8.7) days. The mortality rate was 7.1%. Older age and presence of biliary disease were associated with mortality. CONCLUSIONS: The low mortality of our patients was probably related to the high proportion of patients who received catheter drainage. Older age and presence of biliary disease were associated with the mortality. PMID- 17335657 TI - Effect of parenteral glutamine supplementation in premature infants. AB - BACKGROUND: Glutamine, proposed to be conditionally essential for critically ill patients, is not added routinely to parenteral amino acid formulations for premature infants and is provided in only small quantities by the enteral route when enteral feeding is low. Parenteral feeding is the basic way of nutrition in the first days of life of premature infants. In this study, we evaluated the effects of glutamine supplemented parenteral nutrition for premature infants on growth and development, feeding toleration, and infective episodes. METHODS: From December 2002 to July 2006, 53 premature infants were given either standard or glutamine supplemented parenteral nutrition for more than 2 weeks. Twenty-eight infants were in glutamine supplemented group, whose gestational age (31.4 +/- 2.0) weeks, birth weight range (1386 +/- 251) g; twenty-five infants were in control group, gestational age (31.1 +/- 1.7) weeks, with birth weight range (1346 +/- 199) g. There were no differences between the two groups. Various growth and biochemical indices were monitored throughout the duration of hospital stay. Data between groups were analyzed with Student's t test. Nonparametric data were analyzed using a Chi-square test. A two-tailed P value < 0.05 was considered statistically significant. RESULTS: The level of serum albumin was lower in the glutamine groups on the second week (3.0 vs 3.2 g/dl, P = 0.028), and blood urea nitrogen was higher in glutamine groups on the fourth week (8.1 vs 4.9 mg/dl, P = 0.014), but normal. Glutamine group infants took fewer days to regain birth weight (8.1 vs 10.4 days, P = 0.017), required fewer days on parenteral nutrition (24.8 vs 30.8 days, P = 0.035), with shorter stays in hospital (32.1 vs 38.6 days, P = 0.047). Episodes of hospital acquired infection in glutamine supplemented infants were lower than that in control group (0.96 vs 1.84 times, P = 0.000). CONCLUSION: Parenteral glutamine supplementation in premature infants can shorten days on parenteral nutrition and length of stay in hospital, and decrease hospital acquired infection episodes. PMID- 17335659 TI - Cytokine production during the inhibition of acute vascular rejection in a concordant hamster-to-rat cardiac xenotransplantation model. AB - BACKGROUND: The aim of the current study was to investigate the role of interleukin (IL)-2, interferon (IFN)-gamma, IL-4 and IL-10 in a concordant hamster-to-rat cardiac xenotransplantation model. METHODS: A hamster-to-rat cardiac transplantation was performed using SD rats as recipients of Golden Syrian hamster hearts. A total of 60 SD rats were divided into four groups and treated as follows: control group (n = 15); splenectomy group (n = 15); CsA group (n = 15); CsA + splenectomy group (n = 15). Levels of IL-2, IFN-gamma, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Sera were harvested at different time points in each group: day 1, and 3 as well as the day the xenograft stopped beating in the control group and CsA group; day 1, 3, 7, 14 and 30 in the splenectomy group and CsA + splenectomy group. The expression of P selectin and intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemical analysis of the xenograft after cardiac xenotransplantation. RESULTS: Serum levels of IL-2 and IFN-gamma were upregulated in untreated (day 3) and splenectomy-treated animals (day 7) compared to CsA + splenectomy treated animals (day 7). IL-10 was upregulated in long-term survival recipients following splenectomy + CsA. Neither P-selectin nor ICAM-1 expression was detected in long term survival xenografts. CONCLUSIONS: Serum IL-2 and IFN-gamma were elevated following acute vascular rejection. Serum IL-10 was correlated to immunosuppression and protective effects in long-term survival rats following concordant cardiac xenotransplantation. PMID- 17335661 TI - Modulation of KCNQ1 current by atrial fibrillation-associated KCNE4 (145E/D) gene polymorphism. AB - BACKGROUND: Atrial fibrillation is a common arrhythmia with multi-factorial pathogenesis. Recently, a single nucleotide polymorphism (G/T) at position 1057 in the KCNE4 gene, resulting in a glutamic acid (Glu, E)/aspartic acid (Asp, D) substitution at position 145 of the KCNE4 peptide, was found in our laboratory to be associated with idiopathic atrial fibrillation (atrial fibrillation more frequent with KCNE4 145D). However, the functional effect of the KCNE4 145E/D polymorphism is still unknown. METHODS: We constructed KCNE4 (145E/D) expression plasmids and transiently co-transfected them with the KCNQ1 gene into Chinese hamster ovary-K1 cells and performed whole-cell patch-clamping recording to identify the possible functional consequences of the single nucleotide polymorphism. Quantitative data were analyzed by Student;s t test. Probability values less than 0.05 were considered statistically significant. RESULTS: A slowly activating, non-inactivating voltage-dependent current ((24.0 +/- 2.9) pA/pF, at +60 mV)) could be recorded in the cells transfected with KCNQ1 alone. Co-expression of wild type KCNE4 inhibited the KCNQ1 current ((7.3 +/- 1.1) pA/pF)). By contrast, co-expression of KCNE4 (145D) augment the KCNQ1 current ((42.9 +/- 7) pA/pF)). The V(1/2) of activation for the KCNQ1/KCNE4 (145D) current was shifted significantly towards the depolarizing potential compared to that for the KCNQ1 current ((-2.3 +/- 0.2) mv vs (-13.0 +/- 1.5) mv, P < 0.01)) without changing the slope factorkappa. Furthermore, KCNE4 (145D) also affected the activation and deactivation kinetics of KCNQ1 channels. CONCLUSION: We provide experimental evidence that the KCNE4 (145E/D) polymorphism exerts the effect of "gain of function" on the KCNQ1 channel. It may underlie the genetic mechanism of atrial fibrillation. Further studies on the functional association between I(Ks) and KCNE4 (145D) polymorphism in cardiac myocytes are suggested. PMID- 17335662 TI - Effect of dexamethasone on peroxisome proliferator activated receptor-gamma mRNA expression in 3T3-L1 adipocytes with the human recombinant adiponectin. AB - BACKGROUND: The fat derived protein adiponectin plays an important role in the regulation of glucose metabolism. The aim of this study was to provide the experimental basis for further investigating on adiponectin (ADPN) function. Its eukaryotic recombinant was constructed and expressed in precursor cells of 3T3-L1 adipocytes. The effects of dexamethasone on peroxisome proliferator activated receptor-gamma (PPAR-gamma) mRNA expression in 3T3-L1 cells with human recombinant adiponectin were assessed. METHODS: The recombinant plasmid pMD18-T hADPN and eukaryotic expression vector pcDNA3.1(+) were digested by two restrictive endonucleases and adiponectin and linear pcDNA3.1(+) were obtained. Then, they were ligated and translated into JM109. The recombinant pcDNA3.1(+) hADPN so obtained was identified by digestion by restrictive endonuclease and nucleotide sequencing. The 3T3-L1 precursor cells were transfected using SuperFect Transfection Reagent (Qiagen). Furthermore, 3T3-L1 cells with human recombinant adiponectin incubated with dexamethasone (0.5 mmol/L) for 24 hours, cells were collected and total RNA was extracted. The PPAR-gamma mRNA expression was quantified by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: After eukaryotic recombinant was digested by Hind III and EcoR I, fragments of 800 bp and 5.4 kb were identified by nucleotide sequence scanning and consistent with theoretical values. Electrophoretogram of RT-PCR in 3T3-L1 precursors showed only one band in front of 250 bp, which was consistent with theoretical value 234 bp. In the 3T3-L1 cells, 3T3-L1 cells with plasmid and 3T3-L1 cells human recombinant adiponectin, treatment with dexamethasone (0.5 mmol/L) decreased PPAR-gamma mRNA expression compared to untreated controls (P < 0.01). Effect of dexamethasone on PPAR-gamma mRNA expression in 3T3-L1 cells was reversed by stably transfected human recombinant adiponectin. CONCLUSION: The 3T3 L1 cells stably transfected human recombinant adiponectin had increased PPAR gamma mRNA expression. Dexamethasone suppressed PPAR-gamma mRNA expression in the 3T3-L1 cells. Effect of dexamethasone on PPAR-gamma mRNA expression in 3T3-L1 cells was reversed by stably transfected human recombinant adiponectin. PMID- 17335663 TI - Etiology, treatment, and classification of Budd-Chiari syndrome. PMID- 17335664 TI - Regularity of hypoxia inducible factor 1 alpha expression in acute myocardial ischaemia in rats. PMID- 17335665 TI - Pharmacokinetics of metadoxine for injection after repeated doses in healthy volunteers. PMID- 17335667 TI - Treatment of infrarenal abdominal aortic dissection concomitant with an aneurysm. PMID- 17335668 TI - Variant angina associated with isolated myocardial bridging: evaluation using intravascular ultrasound and quantitative coronary angiography. PMID- 17335669 TI - Noncompaction cardiomyopathy associated with hypogenetic lung. PMID- 17335671 TI - Key points in the management of gastroesophageal reflux disease. PMID- 17335672 TI - Specific targeted antiviral therapy for hepatitis C. AB - Since the discovery of the hepatitis C virus (HCV) as the major cause of non-A, non-B hepatitis in 1989, the search for specific targeted antiviral therapy for HCV (STAT-C) has been underway. Recently, major advances in the understanding of HCV biology and the development of an in vitro system of HCV replication have contributed to the selection of multiple candidate drugs for the treatment of hepatitis C. In 2006, five such candidate drugs have entered phase II clinical trials in patients chronically infected with hepatitis C, including small molecule inhibitors of the HCV NS3 serine protease and NS5B RNA-dependent RNA polymerase. This review focuses on hepatitis C protease and polymerase inhibitors that have progressed to phase II clinical development, foreshadowing the era of STAT-Cs. PMID- 17335673 TI - Improving outcomes for patients with chronic hepatitis B. AB - The ultimate goal in managing patients with chronic hepatitis B (CHB) is to improve long-term outcomes by decreasing deaths and liver transplantation procedures due to hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma. Active intervention and vaccination of individuals susceptible to HBV infection are key steps to decrease the risk of this global public health problem. Large studies have demonstrated that long-term outcomes of CHB are tied to serum levels of HBV DNA. New oral treatments, characterized by potent antiviral effects, good tolerability, improved histology, stable seroconversion, and minimal resistance, are available. Long-term data with oral medications have shown decreased rates of liver cancer development, liver disease reversal, and progression to liver failure. Pegylated interferon trials have demonstrated modest rates of hepatitis B e antigen seroconversion and improved histology after treatment. This paper describes ways to improve outcomes of CHB using vaccines, interferon, lamivudine, adefovir, and newer agents. PMID- 17335674 TI - Approach to recurrent hepatitis C following liver transplantation. AB - Hepatitis C-associated liver failure is the most common indication for liver transplantation. Histologic evidence of recurrence is apparent in approximately 50% of hepatitis C virus (HCV)-infected recipients in the first postoperative year. Approximately 10% of HCV-infected recipients will die or lose their allograft due to hepatitis C-associated allograft failure. HCV-infected recipients who undergo retransplantation have 5-year patient and graft survival rates that are broadly similar to those for transplant recipients who are not HCV infected. Although the choice of calcineurin inhibitor, mycophenolate mofetil, or both has not been clearly shown to affect histologic recurrence of hepatitis C, higher cumulative exposure to corticosteroids is associated with increased mortality and more severe histologic recurrence. In contrast to treatment of non HCV-infected recipients, treatment of HCV-infected transplant recipients for acute cellular rejection is associated with attenuated patient survival. Steroid resistant rejection with or without the use of T-cell-depleting therapies is associated with a greater than fivefold increased risk of mortality in HCV infected liver transplant recipients. Pegylated interferon with or without ribavirin should be considered for treatment of recipients with histologically apparent recurrence of hepatitis C before total bilirubin exceeds 3 mg/dL. The role of hepatitis C immunoglobulin and new immunosuppressive agents in the management of hepatitis C after transplant continues to evolve. PMID- 17335675 TI - Management of biliary complications following orthotopic liver transplantation. AB - Biliary complications are a major cause of morbidity following orthotopic liver transplantation with an overall incidence between 11% and 25%. The most common complications are biliary leaks, strictures, and stones. These complications have an impact on graft survival, length of hospital stay, recovery, and overall cost of care. Therefore, knowledge of these complications and their management is important to the practicing gastroenterologist. Historically, biliary complications after liver transplantation have been managed surgically. However, with the growth of therapeutic endoscopic and percutaneous radiologic methods, most of these complications can now be managed less invasively. This article focuses on the incidence, timing, mechanism, and endoscopic management of biliary leak, strictures, stones, sludge, casts, and sphincter of Oddi dysfunction following liver transplantation. PMID- 17335676 TI - Alcoholic steatohepatitis: management and prognosis. AB - Alcoholic hepatitis is a disease with a wide range of severity. Patients with severe disease have short-term mortality rates above 35%. In these high-risk patients, pharmacologic therapy is an important adjunct to supportive medical care and has been proved to improve survival. Given the benefit of drug treatment, it is important to identify patients at risk of early mortality from alcoholic hepatitis. A number of validated scoring systems are useful for this purpose, including the Maddrey Discriminant Function, the Model of End-Stage Liver Disease score, and the Glasgow Alcoholic Hepatitis score. Patients judged by one or more of these criteria to have severe alcoholic hepatitis should be treated with corticosteroids or pentoxifylline, provided they have no contraindications for this treatment. Adequate nutrition is also critical and should be provided by tube feeding if necessary. A prompt decline in serum bilirubin indicates a favorable response to therapy. Patients who do not exhibit a reduction in serum bilirubin within 1 week are considered nonresponders and have a 6-month mortality rate of 50% or higher. PMID- 17335677 TI - Treatment of fibrosis in nonalcoholic fatty liver disease. AB - Nonalcoholic steatohepatitis (NASH) is one of the most common liver disorders in North America. The mechanism of liver injury in NASH involves insulin resistance and oxidative stress as well as cytokine release. Therapeutic interventions aimed at enhancing insulin sensitivity or reducing oxidative stress have been studied. The role of peptide hormones secreted by adipose tissue--adipocytokines--in the potential pathogenesis of NASH is an area of intense research. As the function of adipokines in modulating hepatic inflammation and fibrosis is elucidated, the potential for novel treatment strategies in patients with NASH is likely to be realized. PMID- 17335678 TI - High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. AB - Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that results in progressive fibrosis of intrahepatic and extrahepatic bile ducts. No effective therapy currently exists for this disease. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is the most promising treatment option because of its benign side effect profile and documented benefit in the treatment of other cholestatic liver diseases, including primary biliary cirrhosis. Multiple studies using standard-dosage (8-15 mg/kg/d) and high-dosage (20-30 mg/kg/d) UDCA generally show improvement in liver chemistries in PSC patients, and several show improvement in liver histology. However, the majority of trials using UDCA in PSC are underpowered and fail to show improvements in clinically relevant endpoints, such as delayed progression to cirrhosis, portal hypertension, liver transplantation, development of cholangiocarcinoma, or death. PMID- 17335679 TI - Hepatic complications of hematopoietic cell transplantation. AB - Acute and chronic liver disease contributes significantly to morbidity and mortality following hematopoietic cell transplantation (HCT). The best prognostic indicator for the development of severe liver dysfunction is an early rise in liver function test results after HCT. The leading causes soon after HCT are acute graft-versus-host disease (GVHD), sinusoidal obstruction syndrome, drug and total parenteral nutrition hepatotoxicity, sepsis, and viral infection. Hepatic herpesvirus and fungal infections after HCT, though uncommon, can be life threatening and warrant immediate diagnosis and treatment. Hepatitis B, hepatitis C virus, iron overload, and chronic GVHD are among the most common causes for chronic liver disease after HCT. Because treatments are directed at the underlying etiology of liver disease, prompt diagnosis by means of laboratory tests, hepatic imaging, and often liver biopsy is required after HCT. PMID- 17335680 TI - Epidemiology of acute liver failure. AB - Acute liver failure (ALF) is an uncommon disorder that leads to jaundice, coagulopathy, and multisystem organ failure. Its definition is based on the timing from onset of jaundice to encephalopathy. In 2005, ALF accounted for 6% of liver-related deaths and 7% of orthotopic liver transplants (OLT) in the United States. Several classification systems have been developed for ALF, with the King's College criteria most widely used for prediction of OLT. Specific diagnostic tests should be implemented to identify the cause of ALF, which will help to determine its treatment and prognosis. Viral hepatitis was previously reported to be the most common cause of ALF in the United States, but acetaminophen overdose and idiosyncratic drug reactions have emerged as the most frequent causes in recent studies. Malignancy is an uncommon cause of ALF, and thus imaging studies may not be useful in this setting, but liver biopsy may be beneficial in selected cases. An overall strategy for ALF should start with identifying the cause, assessing the prognosis, and early transfer to a transplantation center for suitable candidates. OLT has emerged as a life-saving procedure leading to marked improvement in survival rates. Improved surgical techniques, immunosuppression, and comprehensive care have led to an overall survival rate of approximately 65% with OLT. N-acetylcysteine is effective in ALF caused by acetaminophen overdose, with results strongly related to how soon it is given rather than the route of administration. Liver support systems show potential for the treatment of ALF, but their role needs validation in large multicenter randomized trials. PMID- 17335681 TI - Chelation therapy for iron overload. AB - Iron overload is characterized by excessive iron deposition and consequent injury and dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Because physiologic mechanisms to excrete iron are very limited, patients with iron overload and its complications need safe, effective therapy that is compatible with their coexisting medical conditions. The availability of three licensed iron chelation drugs (one parenteral, two oral) and the development and clinical investigation of other oral chelators represent new opportunities to prevent or manage iron overload in patients with heritable types of severe anemia, such as beta-thalassemia major and sickle cell disease, and for the formulation of alternatives to phlebotomy therapy for patients with iron overload associated with the HFE gene and other adult age-of-onset types of hemochromatosis, African iron overload, and African-American iron overload. PMID- 17335682 TI - Hepatitis C and HIV. AB - HIV and hepatitis C virus (HCV) are global health concerns, and coinfection with these viruses is common due to shared routes of transmission. Mortality rates from AIDS and HIV-associated opportunistic infections have decreased since the institution of highly active antiretroviral therapy, but the incidence of liver related mortality in coinfected patients has subsequently risen significantly. This increase in progression of liver disease and its subsequent increased mortality have spurred research into the optimization of evaluation and management of the HIV-HCV coinfected patient. PMID- 17335683 TI - Multiple myeloma. Clinical practice guidelines in oncology. PMID- 17335684 TI - The emerging role of novel therapies for the treatment of relapsed myeloma. AB - Despite advances in the first-line treatment of multiple myeloma, almost all patients eventually relapse, become chemoresistant, and die of the disease. Improved understanding of potential myeloma targets and molecular mechanisms of drug resistance, along with the development and clinical investigation of targeted antitumor agents, have led to new strategies for the treatment of relapsed myeloma. The proteasome inhibitor bortezomib, the immunomodulatory agent thalidomide, and the thalidomide derivative lenalidomide, are all recently approved treatment options for myeloma. Single-agent bortezomib has been shown to provide significantly greater efficacy than high-dose dexamethasone, and bortezomib has also been investigated in combination with other agents commonly used to treat myeloma, including thalidomide and lenalidomide, with high overall and complete response rates. The safety profile of bortezomib has been well characterized, and side effects have been shown to be generally predictable and manageable, including in high-risk and elderly patients and those with renal impairment. Thalidomide has been extensively studied alone and in combination in patients with relapsed myeloma, demonstrating substantial efficacy, and is therefore widely used in this setting. The toxicity profile is dose- and duration linked, with lower doses appearing to be better tolerated. Lenalidomide plus dexamethasone has been shown to have significantly greater activity than dexamethasone alone in the relapsed setting, with impressive duration of disease control. Other combinations are also under investigation, with promising early results. Some aspects of the toxicity profile appear significantly reduced relative to thalidomide, although myelosuppression is increased. Other novel therapies at earlier stages of development are being studied and may provide further options in the treatment of relapsed myeloma. This review focuses on results from key phase II and III trials of bortezomib, thalidomide, and lenalidomide alone or in combination, and their emerging role in improving outcomes. PMID- 17335685 TI - Role of bone marrow transplantation in the disease pathway of myeloma. AB - In multiple myeloma, autologous stem cell transplantation (ASCT) has been considered a standard of care in younger patients. The introduction of novel agents (i.e., thalidomide, lenalidomide, and bortezomib) may change this scenario. These agents can be administered before or after ASCT with the goal of increasing the complete remission (CR) rate and prolonging remission. For instance, thalidomide given as maintenance therapy after double ASCT increases CR rate, event-free survival (EFS), and overall survival. Moreover, combinations of conventional chemotherapy with novel agents such as thalidomide or bortezomib yield CR rates and EFS comparable to those achieved with standard single ASCT. Prospective randomized studies are needed to evaluate the impact of novel agents versus or in combination with ASCT. Myeloablative conditioning regimens before allogeneic stem cell transplantation are being replaced with concurrent autologous-transplantation and reduced-intensity conditioning allogeneic stem cell transplantation. Transplant-related mortality associated with this procedure is lower, but more follow-up is needed before definite conclusions can be drawn. PMID- 17335686 TI - Multiple myeloma: most common end-organ damage and management. AB - End-organ damage is the factor that differentiates plasma cell dyscrasia requiring therapy (active multiple myeloma [MM]) from disease that does not require therapy (monoclonal gammopathy of undetermined significance and smoldering [asymptomatic] MM). Progressive skeletal destruction is the hallmark of MM and responsible for principle morbidity in the disease. The spine is the most afflicted skeletal organ, and vertebral fractures have significantly contributed to its poor prognosis. Early mortality in MM is usually attributed to the combined effects of active disease and comorbid factors. Infection and renal failure are the main direct causes of early mortality. Using bisphosphonates to manage skeletal events mainly by preventing or slowing the destructive process has become an important adjunctive treatment in MM. Advances in minimally invasive surgical techniques, such as percutaneous vertebroplasty and kyphoplasty, offer these patients less-invasive options for treating vertebral collapse and restoring function. The aggressive management of other complications of the disease through more effective and less toxic therapy that targets the primary disease, in addition to supportive care, is resulting in patients experiencing less morbidity and probably lower mortality. This article reviews recent advances in the understanding of bone disease in MM, the role of bisphosphonates in preventing skeletal events, and available data on percutaneous vertebroplasty and kyphoplasty, and discusses the management of infection and renal failure, which seem to be responsible for high initial mortality and thereby compromise the current advances in therapy. PMID- 17335687 TI - Managing systemic light-chain amyloidosis. AB - Amyloidosis is a rare disease in which a specific protein is deposited as aggregated interstitial fibrils that can compromise organ function and lead to death. Immunoglobulin (Ig) light-chain amyloidosis (AL), caused by the monoclonal gammopathy of a plasma cell dyscrasia, is the most common type. A hereditary type is also caused by mutant transthyretin and other proteins. Rarely, a patient with amyloid has both a monoclonal gammopathy and a hereditary protein. In AL, circulating monoclonal Ig light chains can be measured with the free light-chain (FLC) assay and provide a target for therapy to eliminate the underlying plasma cell dyscrasia while supporting the patient's organ function. Amyloid deposits can be resorbed and organ function restored if the amyloid-forming precursor FLC is eliminated. For patients with limited organ involvement, intravenous melphalan in doses from 100 to 200 mg/m2 with autologous stem cell support (SCT) is an effective approach and, when followed at 3 months post-SCT with adjuvant thalidomide and dexamethasone for persistent plasma cell disease, has a 1-year hematologic response rate of 77%. Monthly oral melphalan and dexamethasone for 1 year can also be effective therapy for patients too sick for SCT (67% response rate). Hematologic complete responses are usually durable and result in long-term survival and a variable degree of organ recovery. For patients with advanced cardiac involvement, the prognosis remains guarded even with treatment. Drugs effective in multiple myeloma are usually active in AL, depending on side effects. New agents such as bortezomib and lenalidomide have shown promising activity, and novel antibody-based approaches for imaging amyloid and accelerating removal of deposits are being actively investigated. PMID- 17335688 TI - Myeloid growth factors. Clinical practice guidelines in oncology. PMID- 17335689 TI - Growth factors in leukemia. AB - The role of myeloid growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, in the management of acute myeloid and acute lymphoblastic leukemias has been evaluated extensively in multiple clinical trials. Growth factors have been given before, concurrently, or sequentially with chemotherapy with the goal of reducing the duration of neutropenia and consequently the incidence and severity of infections, and improving the rate of remissions and overall survival. They also have been studied as chemotherapy-sensitizing agents in an effort to recruit dormant myeloid stem cells into the sensitive phase of the cycle. Additionally, growth factors, shown to stimulate proliferation and differentiation of leukemia cells in vitro, were evaluated as monotherapy in patients with acute leukemia. Most studies show modest improvement in the duration of the neutropenia, which does not consistently correlate with the severity of infection, rate or duration of remissions, or disease-free and overall survival. Attempts to enhance the chemosensitivity of the leukemic cells and decrease drug resistance failed to improve the rate of remission and survival in several large series. However, more recent reports suggested an improved outcome in younger patients with acute myeloid leukemia with normal karyotype. Several anecdotal case reports have shown that growth factor monotherapy can induce a complete remission in patients with acute leukemia. Data from the published clinical trials do not seem to support emergence of drug-resistant leukemia, worsening toxicity, and bone marrow failure with growth factor administration. PMID- 17335690 TI - Summary and comparison of myeloid growth factor guidelines in patients receiving cancer chemotherapy. AB - Three different practice guidelines for the myeloid growth factors were recently published by major professional organizations. A comprehensive review and comparison of the guidelines using a priori structured content criteria and a previously validated quality appraisal tool are reported. The final recommendations from these guidelines are consistent for primary prophylaxis with the colony-stimulating factors (CSFs) when the risk of febrile neutropenia is in the range of 20% or greater. All 3 guidelines also recommend prophylactic use of myeloid growth factors in patients with important factors increasing individual risk of neutropenic complications. The recommendation that patients receiving regimens associated with lower risk should have CSF use guided by individual risk assessment is also consistent. Critical quality appraisal indicates that the scope, purpose, stakeholder involvement, and applicability of these guidelines differ little. The American Society of Clinical Oncology and European Organization for Research and Treatment of Cancer guidelines place more emphasis on comprehensive literature reviews, and the National Comprehensive Cancer Network guidelines are more current based on systematic annual updates. Presentation clarity also favors National Comprehensive Cancer Network guidelines, with recommendations generally presented as both text and algorithmic diagram. PMID- 17335691 TI - Myeloid growth factor therapy for prophylaxis of febrile neutropenia in non myeloid malignancies: appropriate doses and schedules. AB - Myeloid growth factors (MGFs) are used for the prophylaxis of febrile neutropenia and maintenance of scheduled dose delivery in the treatment of patients undergoing cancer chemotherapy. To spare cost and for patient convenience, in adults MGFs are used at schedules, doses, and durations that differ from the approved prescribing information of the U.S. Food and Drug Administration. These variations include rounding doses to convenient sizes, fewer days of treatment, a shorter interval between cycles, and same-day administration with chemotherapy. Some of these variations are supported by clinical trial results and practice guidelines. PMID- 17335692 TI - Antibacterial prophylaxis in patients with neutropenia. AB - Patients with cancer and chemotherapy-induced neutropenia are at risk for severe bacterial infections. This risk is not uniform among all cancer patients but is dependent primarily on the depth and duration of neutropenia and the type of underlying disease. Accordingly, the decision whether to use antibacterial prophylaxis to prevent serious infections in these patients requires a balance between expected benefit and the risks for infection, adverse drug-related events, and emergence of antibiotic resistance. Although antibacterial prophylaxis has the potential to benefit all patients with chemotherapy-induced neutropenia, the benefit regarding reduction in documented infections has been firmly established only in patients with neutropenia expected to exceed 7 days. A recent meta-analysis showed enhanced survival in patients receiving antibacterial prophylaxis during neutropenia; most patients enrolled in the analyzed trials had a hematologic malignancy. Among patients with neutropenia at lower risk for infectious complications (a category that includes most patients with solid tumor malignancies), the main benefit of antibacterial prophylaxis relates to a reduction in fever rather than documented infections. The authors advise quinolone prophylaxis (levofloxacin is preferred), in patients with an expected duration of neutropenia (absolute neutrophil count < 1000/microL) of more than 7 days. Trimethoprim-sulfamethoxazole should be used in patients at risk for Pneumocystis jiroveci (formerly P carinii), such as childhood acute lymphoblastic leukemia. In patients with neutropenia expected to last 7 days or less and not receiving immunosuppressive regimens (e.g., systemic corticosteroids), the authors recommend no initial prophylaxis. However, if such patients develop fever during neutropenia, they should be considered for outpatient empiric therapy with an oral quinolone-containing regimen if they meet criteria for low risk for complications. PMID- 17335693 TI - [Q fever: still many unanswered questions]. PMID- 17335694 TI - [Imported malaria in a general hospital in Madrid]. AB - INTRODUCTION: To study the clinical and epidemiological characteristics of malaria and the diagnosis of this condition in a general hospital that does not have a specialized tropical medicine unit. METHODS: Retrospective study of all malaria cases diagnosed by thick film and/or PCR-positive status for any Plasmodium spp. from 1999 to 2003 in Hospital Principe de Asturias in Alcala de Henares (Madrid, Spain). RESULTS: Over the period studied, 89 cases of malaria were diagnosed. Most patients were African immigrants who had recently left their countries of origin (52%), or immigrants residing in Spain who had traveled to Africa for a short visit (35%) and did not take prophylaxis. The distribution of cases by species was Plasmodium falciparum 89%, P. ovale 7% and P. malariae 4%. Clinical data were non-specific and the percentage of severe complications was low (6.7%). A second-generation test for rapid detection of P. falciparum antigen (PfHRP2) was studied in a group of 46 patients with suspected malaria; the results obtained were similar to thick film as compared to PCR for diagnosing P. falciparum infection. CONCLUSIONS: Access to information on prevention and chemoprophylaxis should be available to all travelers, particularly immigrants visiting their countries of origin. Most semi-immune patients with uncomplicated malaria can be treated on an outpatient basis. PfHRP2 antigen detection, a fast, reliable method for diagnosing malaria due to P. falciparum, can be used in addition to the thick film method in our setting. PMID- 17335695 TI - [Clinical assessment of Monolisa HCV Ag-Ab ULTRA (Bio-Rad) in a general hospital]. AB - INTRODUCTION: To evaluate a new test based on simultaneous detection of HCV antibodies and antigen (Monolisa HCV Ag/Ab ULTRA; Bio-Rad, Marnes la Coquette, France). METHODS: We studied samples from two groups of patients and 7 commercial HCV seroconversion panels (75 samples). Group 1: 1360 serum samples from patients referred for routine testing of anti HCV antibodies. Group 2: 333 serum samples from 183 hemodialysis patients. All samples were tested by the Ortho HCV 3.0 technique (Ortho-Clinical Diagnostics, Amersham, UK) and the Monolisa HCV Ag-Ab ULTRA technique. RESULTS: Group 1: Seventy-four of 1360 serum samples were positive by Ortho HCV and 77 by Monolisa. In 1353 samples, the results with the two tests were concordant: 1281 negative and 72 positive. Five samples were positive only by Monolisa and 2 only by Ortho (overall agreement: 99.5%). Group 2: Results were concordant in 325 samples, 308 negative and 17 positive. Seven samples were positive by Monolisa and negative by Ortho. The sensitivity of the Monolisa test in hemodialysis patients was clearly higher than that of the Ortho test (100% and 70.8%, respectively). Monolisa detected HCV infection in 43 of 75 samples from the seroconversion panels; only 18 positive samples were detected by Ortho HCV. Monolisa reduced the window period by up to 72 days. CONCLUSIONS: Our data indicate high agreement between the Monolisa and Ortho tests in samples from the general population. In hemodialysis patients, however, Monolisa was more sensitive. In addition, the Monolisa test significantly reduced the window period of HCV infection. PMID- 17335696 TI - [Influenza virus in pediatrics. A reason for hospitalization]. AB - INTRODUCTION: Influenza infection in infants and children has been classically underestimated due to its non-specific symptoms, which sometimes overlap those of other respiratory viruses. Infants under 24 months are a risk group and school aged children are a major source of influenza infection. The aim of this study was to describe the clinical and epidemiological characteristics of children hospitalized for flu, including co-infections and the differences as compared to other respiratory viruses. The effectiveness of a test for rapid diagnosis of this condition was assessed. MATERIAL AND METHODS: Prospective, descriptive study in children < 5 years of age hospitalized from 1 December 2003 to 28 February 2004 with respiratory processes or fever of unknown origin. Polymerase chain reaction (PCR) testing for influenza A (IA) and B, respiratory syncytial virus A (RSV-A) and B, and parainfluenza 1, 2 and 3 was performed in nasopharyngeal aspirate, as well as a test for rapid diagnosis of influenza. RESULTS: A total of 203 samples were included. PCR was positive for influenza in 11.3% (23/203); IA in 21 cases (20 H3N2, 1 H1N1). Co-infections were frequent (10/23), mainly IA with RSV-A. The rapid diagnostic test had a sensitivity of 45.5%. Median age of patients with flu was 4.87 months (5 days-3.5 years); 69.5% were < 24 months. Gastrointestinal symptoms were associated with fever and respiratory symptoms more often than in other viral infections (P < 0.05). Only 2.9% of patients with a recommendation for flu vaccination had received the vaccination. CONCLUSIONS: Flu is a major cause of hospitalization in infants and children, particularly those aged < 24 months. Early diagnosis of this condition may avoid unnecessary use of additional tests and antibiotics. Vaccination coverage is low; vaccination between 6 and 24 months seems advisable. PMID- 17335697 TI - [Outbreak of Coxiella burnetii pneumonia]. AB - OBJECTIVE: The aim of this study was to describe an outbreak of Q fever pneumonia in the North of Spain. MATERIAL AND METHODS: We report 60 cases of Coxiella burnetii pneumonia in a rural area with 16,000 inhabitants during January and February 2003. The diagnosis was serologically confirmed by indirect immunofluorescence. RESULTS: Mean age of the patients was 46 years and the male/female ratio was 2.5. Overall, 52% of the patients lived in urbanized areas and contact with animals was declared in only 7% of patients. Sixty percent of patients were hospitalized. The most frequent clinical presentation was an acute febrile process (100%) and headache (80%); respiratory symptoms were infrequent. The most common liver function alteration was elevated transaminase levels (35%). Radiologic evidence of a single lobar or segmental alveolar opacity was found in 87% of patients, and most commonly affected the lower lobes. Chest radiographs returned to normal in 70% of patients within the two first months. Empirical treatment consisted of beta-lactams and macrolides in 38%, macrolides alone in 8%, and quinolones in 23%; 27% were treated with beta-lactams alone. No deaths occurred. CONCLUSIONS: Coxiella burnetii infection is very prevalent in the north of Spain and should be suspected and investigated when outbreaks of a pneumonic illness occur. PMID- 17335698 TI - [Age-dependent seroprevalence of Toscana virus in the Community of Madrid: 1993 1994 and 1999-2000]. AB - OBJECTIVE: The aim of this study was to assess the seroprevalence of Toscana virus (TOSV) in the Community of Madrid. METHODS: Samples from two serosurveys obtained during 1993-1994 (2262 individuals) and 1999-2000 (1945 individuals) were studied. Samples were tested by ELISA for TOSV IgG detection. RESULTS: The seroprevalence of TOSV IgG was significantly higher in 1993-1994 (7.2%; 95% CI 6.2-8.4) than in 1999-2000 (5.7%; 95% CI 4.7-6.9) (chi-square, p < 0.05). In both periods, the prevalence increased significantly with age. CONCLUSION: These results confirm that TOSV has been circulating in the Community of Madrid over the last years. PMID- 17335699 TI - [Biodefense: a new challenge for microbiology and public health]. AB - Bioterrorism and the potential use of biological weapons has become an important concern of governments and responsible authorities. An example of this threat occurred in 2001 in the USA, when letters were sent containing spores of the agent that produces anthrax; this resulted in some deaths, and caused panic and negative effects on the world economy. If this small-scale event was able to cause such a huge impact, the repercussions of a massive attack could be catastrophic. In many countries, these events have resulted in the implementation of measures directed toward preventing and responding to bioterrorist threats and acts. As a whole, these measures are known as biodefense. This article briefly analyzes several aspects related to detecting and identifying acts of bioterrorism, and considers the biological agents that are implicated. The microbiological diagnosis that allows identification of the causal agent, a key point for taking suitable control measures, is also included. PMID- 17335700 TI - Q fever in Logrono: an attack scenario. AB - Bioterrorism has emerged as an important infectious disease and public health challenge in the 21st century, and issues of preparedness and response are now prominent. The development of attack scenarios for assessing this problem contributes to the organization of response systems and identifies aspects that may need to be improved. The authors present an attack scenario involving Q fever in a specific area, the city of Logrono, Spain. The evolution of the outbreak is described and the attempts at diagnosis and implementation of public health measures are outlined. Knowledge of the pathogen in the specific scenario and the ability to directly diagnose the disease it causes may be of help to facilitate a fast response that will contain public unrest and the eventual outcome in terms of morbidity and mortality. PMID- 17335701 TI - [Donor-transmitted infections]. AB - The defence response to infectious agents is compromised in solid organ recipients because of their immunosuppressive treatment. Transmission of infection from a donor organ can result in dysfunction or loss of the allograft, and may lead to death of the recipient if adequate preventive measures are not taken. This potential risk should be thoroughly assessed, particularly in the case of organs from infected donors, in order to optimize organ use without increasing the incidence of graft dysfunction and recipient morbidity and mortality. This article reviews the current knowledge regarding screening for infection in potential donors and discusses risk-benefit considerations related to the use of organs from infected donors. PMID- 17335702 TI - [Magrebian patient with abdominal pain]. PMID- 17335703 TI - [Patient from the Republic of Congo with intermittent ocular pain]. PMID- 17335704 TI - [Isoniazid-induced acute pancreatitis]. PMID- 17335705 TI - [Pegylated-interferon-associated retinopathy]. PMID- 17335706 TI - [Acute phlegmonous gastritis in a patient with AIDS]. PMID- 17335707 TI - [Persistent proteinuria in an HIV-infected hypertensive woman]. PMID- 17335708 TI - [Rapid detection of an outbreak of bronchoscopy-associated colonization by Serratia marcescens]. PMID- 17335709 TI - [Presternal abscess due to Salmonella enterica serovar enteritidis]. PMID- 17335710 TI - Immunological changes at rectal mucosa in appendectomised subjects and inhabitants of developing countries. AB - AIM: It has been suggested that appendicitis protects against ulcerative colitis. We hypothesize that early poor hygiene protects against ulcerative colitis (UC) and predisposes to appendicitis. Our aim was to elucidate the immunological characteristics of rectal mucosa in two populations protected against UC development: appendectomised subjects and inhabitants of developing countries. METHODS: this was an age-matched prospective case-control study. Each consecutive individual case appendectomised (group A) was compared to another control from a developing country (group B) and to a control from the general population (group C). Four biopsies from rectal mucosa were taken from all subjects, two for histological and two for histochemical study; specific antibodies were used for T lymphocytes CD3+, CD4+, CD8+ and B lymphocytes CD20+ populations. RESULTS: Mucosa samples of 45 non-smoker healthy subjects were studied, of which 15 were from group A, 15 from group B and 15 from group C. In appendectomised subjects, the proportion of CD8+ cells was higher than in the control group (p<0.001), but similar to that in B group. The proportion of CD3+ and CD20+ cells was significatively lower than in Ecuadorians, but similar to the control group. In Ecuadorians, the proportion of CD3+ and CD8+ cells was significatively higher than in the control group (p<0.001), and were similar to that of CD20+. There were no significant differences in the proportion of CD4+. CONCLUSION: Appendectomy and deficient environmental hygiene are associated with an increase of CD8+ T lymphocytes in the rectal mucosa. Moreover, deficient environmental hygiene is associated with an increase of CD3+ and CD8+ lymphocytes. The CD8+ increase is the only common significant alteration in the mucosa of both groups protected against the development of ulcerative colitis, suggesting that the factors causing changes in lamina propria lymphocytes of both groups are different. PMID- 17335711 TI - [Effectiveness of percutaneous drainage in the treatment of abdominal fluid collections in inflammatory pancreatic disease]. AB - AIMS: To assess the effectiveness of ultrasonography-guided percutaneous drainage (UGPD) in the management of fluid collections (FC) in acute and chronic pancreatitis, and to evaluate factors associated with treatment results. METHOD: Seventy-two patients with pancreatic fluid collections ranging from 5 to 20 cm (median 9 cm) were studied. There were 27 type I pseudocysts (PC), 12 type II PC, 13 type III PC, 16 abscesses, and 4 acute fluid collections. Catheters were placed in 60 patients and simple aspiration was performed in 8 patients. UGPD could not be performed in 4 patients. RESULTS: UGPD was curative in 39 patients (54.1%): 44.4% in type I PC, 83% in type II PC, 30.7% in type III PC, 62.5% in abscesses, and 75% in acute FC. Resolution was achieved in 35.7% of patients with pancreatic duct communication and in 71.4% of those with non-communicated FC. No differences in effectiveness were observed according to the etiology of pancreatitis, pancreatic duct obstruction, drainage method, or the number or size of FC. UGPD was effective in 45.8% of the procedures performed before 1993, in 58.3% of those performed between 1993 and 1999, and in 63.6% of those performed after 2000. The complication rate was 37.5% and all complications were mild. CONCLUSIONS: UGPD is an effective treatment for pancreatic FC. The effectiveness of this method depends on appropriate patient selection and careful management of acute pancreatitis. Outcomes were less favorable in patients with type III PC and in those with duct communication. PMID- 17335712 TI - [Acute hepatitis associated with Colpachi intake. Apropros of 5 cases]. AB - The use of herbal medicines believed to have therapeutic properties is becoming increasingly widespread. These medicines are usually taken by patients on their own initiative and physicians are often unaware of which patients are taking these substances. Herbal medicines can be taken in the form of teas, powders, and liquid extracts. In the last few years, it has come to light that these natural remedies are not free of risks, especially the risk of interaction with other drugs or hepatotoxicity, ranging from asymptomatic forms to massive hepatic necrosis. We describe a series of 5 patients notified to the Spanish Pharmacovigilance System of medicinal products for human use. All the patients developed acute hepatitis during Colpachi treatment lasting several months, which resolved after discontinuing intake of this substance. Systematic examination of the literature revealed the existence of 6 other reported cases of suspected Colpachi-induced hepatotoxicity. PMID- 17335713 TI - [Acute appendicitis in inactive extensive ulcerative colitis]. AB - Appendectomy is associated with a reduced risk of developing ulcerative colitis (UC). In addition, there may be appendicular involvement in UC in patients with extensive or even left-sided disease. However, no data are available on the incidence, clinical presentation and outcome of acute appendicitis in patients previously diagnosed with UC. The impact of appendectomy in this subset of patients also remains to be determined. We describe 2 cases of acute appendicitis in the setting of inactive extensive ulcerative colitis and compare their histologic features with those of the surgical specimens of 2 further UC patients colectomized for refractory and extensive disease. PMID- 17335714 TI - [Heterotopic gastric mucosa in the upper esophagus. An unknown cause of dysphagia]. AB - Heterotopic gastric mucosa in the proximal third of the esophagus is an embryological lesion that has been described in between 1.1% and 10% of gastroscopies. Although most of these lesions are asymptomatic, they can sometimes be accompanied by upper esophageal symptoms due to acid secretion. We present a case of heterotopic gastric mucosa in the proximal third of the esophagus with dysphagia. pH-metry demonstrated acid secretion by these lesions, which was resolved by treatment with proton pump inhibitors. PMID- 17335715 TI - [Physiopathology of bacterial translocation and spontaneous bacterial peritonitis in cirrhosis]. AB - The key pathogenic mechanism initiating spontaneous bacterial peritonitis (SBP) is bacterial translocation (BT), a process through which enteric bacteria cross the intestinal barrier and infect the mesenteric lymph nodes, thus entering the blood circulation and ascitic fluid. The high rate of bacterial translocation in cirrhosis is due to injury to the three pilars composing the intestinal mucosal barrier (the balance of intraluminal bacterial flora, the integrity of the intestinal epithelial barrier, and the local immune system). Blood dissemination and microbial growth in ascitic fluid resulting from SBP are a consequence of damage to the immune system in cirrhosis. Hyperproduction of proinflammatory cytokines and other vasoactive substances contributes to the arterial vasodilation and renal failure that frequently complicate the course of SBP. Even in the absence of SBP, translocation of bacteria and bacterial products from the intestinal lumen contribute to systemic inactivation of immune cells in cirrhosis. PMID- 17335716 TI - [Does antiviral therapy improve the clinical course of cirrhosis due to hepatitis C virus infection?]. AB - Treatment of hepatitis C with pegylated interferon plus ribavirin achieves viral eradication rates of between 50 and 80%. A large number of patients with sustained viral response show fibrosis regression. However, patients without viral response also show improvement. Patients with compensated cirrhosis due to hepatitis C virus can also be successfully treated. In these patients, viral eradication is usually followed by fibrosis non-progression and a reduction of portal hypertension, which undoubtedly modifies the clinical course of the process. In patients without virological response, the ability of antiviral maintenance therapy to alter the natural history of the disease is not clear and three large multicenter studies are currently underway. Preliminary data indicate that patients with cirrhosis treated with interferon as maintenance therapy show less progression than those treated with colchicine. PMID- 17335717 TI - [Lower gastrointestinal bleeding: the great unknown]. AB - Lower gastrointestinal bleeding represents one-fourth of all gastrointestinal hemorrhages. The bleeding usually originates in the colon while less than 10% of cases originate in the small bowel. Colonoscopy is considered the initial procedure of choice due to its diagnostic efficacy, safety, and therapeutic potential. Mesenteric arteriography can be an alternative in patients with massive hemorrhage. Helical computed tomography of the abdomen with endovenous contrast can be useful but has not been directly compared with arteriography. When the results of gastroscopy and colonoscopy are negative, small bowel bleeding is suspected. Capsule endoscopy allows non-invasive examination of the entire small bowel. The diagnostic efficacy of this procedure is clearly superior to that of other conventional examinations and, compared with intraoperative endoscopy, capsule endoscopy has a sensitivity of 95% and a specificity of 75%. Double balloon enteroscopy is a new modality that also allows complete examination of the small bowel with the additional advantage of its therapeutic potential. Definitive diagnosis of the hemorrhagic site is essential for appropriate treatment. Endoscopic and angiographic advances are therapeutic alternatives to surgical resection. Endoscopic treatment is indicated in lesions with active bleeding or signs of recent hemorrhage. Arterial embolization can be a therapeutic alternative when arteriography shows active hemorrhage. Surgical treatment is reserved for patients with persistent bleeding in whom other options have failed. PMID- 17335718 TI - [Elevated transaminase levels in adult celiac disease]. PMID- 17335719 TI - [Value of clinical autopsy and causes of death in liver transplant recipients]. PMID- 17335720 TI - [Acute hepatitis associated with mefloquine therapy]. PMID- 17335721 TI - [Chlorpromazine-induced cholestatic hepatitis in intractable hiccups]. PMID- 17335722 TI - [Lack of usefulness of ABCD score in the early risk of recurrent stroke in transient ischemic attack patients]. AB - BACKGROUND AND OBJECTIVE: Recently a clinical score (ABCD) to identify individuals at high seven-day risk of stroke after transient ischemic attack (TIA) was proposed. The aim of this study was to test this clinical model. PATIENTS AND METHOD: We validated the ABCD score (age > or = 65 years = 1; hypertension = 1; unilateral weakness = 2, speech disturbance without weakness = 1, duration of symptoms in minutes > or = 60 = 2; 10-59 = 1; < 10 = 0) in 325 consecutive TIA patients. Clinical data, symptoms duration, CT scan, and ultrasonographic (carotid and transcranial) findings were collected. Seven-day risk of stroke was recorded. RESULTS: A total of 16 (4.9%) patients had a stroke recurrence within the first seven days after symptoms onset. Six out of 16 (37.5%) strokes occurred in 115 (35.4%) patients with a score of 5 or greater, while the 7-day risk was 4.8% (95% CI 2.04-7.56) in 210 (63.5%) patients with a score less than 5. In cox proportional hazards multivariate analyses only large artery occlusive disease remained an independent predictor of stroke recurrence [hazard ratio = 5.66 (95% CI 2.06-15.57; p = 0.001)]. CONCLUSIONS: Clinical data are not enough to identify patients at higher risk. The combination of clinical, radiological and vascular information may improve the predictive accuracy of stroke recurrence risk. The routine use of combined carotid/transcranial ultrasound testing performed early will be useful for identifying high risk individuals in order to plan urgent aggressive prevention therapies. PMID- 17335723 TI - [Effectiveness and safety of transdermal buprenorphine for chronic pain treatment in the elderly: a prospective observational study]. AB - BACKGROUND AND OBJECTIVE: A number of subjects aged over 65 suffer from some kind of chronic pain. The constant growth of this demographic group makes research of new and efficacious treatment strategies necessary. Transdermal buprenorphine has shown to be a safe and efficacious pharmacotherapy for patients with moderate to severe chronic pain in clinical trials. This paper provides the outcome of this drug in routine clinical practice. PATIENTS AND METHOD: A prospective, uncontrolled observational study that included a 3-month follow-up of patients starting transdermal buprenorphine was performed. Information was collected systematically on pain relief, quality of life (EuroQol-5D questionnaire), comfort of patch use and adverse events. Missing data were imputed by the <>. RESULTS: Out of 1,188 patients with known age, 564 were under 65, 337 were between 65 and 75, and 287 were over 75 years. Within these respective age groups, 63.9%, 66.3% and 67.7% of patients showed <> or <> pain relief; 60.4%, 60.7% and 65.2% showed improvement of sleep quality; and the mean increases of the score of the EuroQol-5D visual analogue scale were 16.0 mm, 15.8 mm and 16.8 mm. Drug-related adverse events were reported in 39.6%, 35.4% and 31.9% of patients, respectively. CONCLUSIONS: This study performed in the routine care setting supports the findings from previous randomised controlled clinical trials of transdermal buprenorphine. PMID- 17335724 TI - [Drug eluting stents: long term results in clinical practice. Comparison between rapamycin and paclitaxel eluting stents]. AB - BACKGROUND AND OBJECTIVE: Drug eluting stents have demonstrated their superiority versus bare metal stents in the reduction of restenosis and major adverse cardiac events. Most studies do not identificate differences between rapamycin and paclitaxel eluting stent. PATIENTS AND METHOD: Retrospective study. We identified all patients treated with rapamycin eluting stents or paclitaxel eluting stents during 2003 and 2004 in our center. We analized major adverse cardiac events incidence in the whole group and we investigated for differences between paclitaxel and rapamicin groups. RESULTS: 170 patients were included. 98 treated with rapamycin eluting stents and 72 with paclitaxel eluting stents. Medium follow up was 365 days. There were no differences between groups in demographic or periprocedural variables. The incidence of major adverse cardiac events was 3.5% in the entire group (2.0% in rapamycin group and 5.6% in paclitaxel group; p = 0.43). CONCLUSIONS: Drug eluting stents show a low incidence of major adverse cardiac events when they are utilized in usual clinical practice. With regard to this, we have not found differences between most used devices in our environment, rapamycin eluting stents and paclitaxel eluting stents. PMID- 17335725 TI - [Renin inhibitors]. PMID- 17335726 TI - [Osteoporosis as a first manifestation of systemic mastocytosis. Study of 6 cases]. AB - BACKGROUND AND OBJECTIVE: We describe 6 cases of secondary osteoporosis due to systemic mastocytosis diagnosed in the last 6 years. RESULTS: Three females and 3 males, age range: 47-66 years, diagnosed with osteoporosis were subsequently diagnosed with systemic mastocytosis. Diagnosis delay: 0.5-17 years. Cutaneous involvement was present in 3 patients, hematologic involvement in 2 patients and gastrointestinal involvement in 2 patients. Histamine levels in urine were elevated in all cases. Four patients had fractures. Treatment with bisphosphonates was started. After 3 years the values of bone mineral density (BMD) improved in the 5 patients evaluated. Two patients had new vertebral fractures and started teriparatide. CONCLUSIONS: Osteoporosis is an unfrequent initial manifestation of systemic mastocytosis. These patients have a high risk of fractures. Our results suggest that although bisphosphonates improve the bone mineral density the risk of fractures persists. PMID- 17335727 TI - [Assistential ethics committees competency and autoevaluation of its components. CEA-CAT (2) study]. PMID- 17335728 TI - [Cytogenetic alterations in meningioma tumors and their impact on disease outcome]. AB - In recent years important advances have been achieved in the understanding of the genetic abnormalities present in meningioma tumors and its association with the ontogeny and progression of these tumor. Accordingly, while the presence of monosomy 22/22q-, associated with mutation of the NF2, BAM22, RRP22, GAR22, MN1, SMARCB1, CLH22 and/or LARGE genes, is associated with neoplasic transformation, other alterations such us monosomy 14, del(1p), different chromosomal abnormalities localized at 9p, 10q and 17q and complex karyotypes are frequently related to tumor progression. From the clinical point of view, currently available information about the impact of the different cytogenetic abnormalities on disease behavior and patient outcome is still scanty; nevertheless, the presence of gains of chromosome 22 in the context of a hyperdiploid karyotype, as well as del(1p) and monosomy 14 have been associated with a statistically significantly shorter recurrence-free survival, this later abnormality showing an independent prognostic value. PMID- 17335729 TI - [Last Ugandan stories or Mamadis triumph]. PMID- 17335730 TI - [Reversible myopathy due to ezetimibe]. PMID- 17335731 TI - [Inferior vena caval filter causing nephritic colic after transmural penetration of the inferior cava]. PMID- 17335732 TI - [Hepatotoxicity associated with the consumption of herbal slimming products]. PMID- 17335733 TI - [Pharmacokinetic interaction between phenitoin and dexibuprofen resulting in acute neurologic toxicity]. PMID- 17335734 TI - [Multiple myeloma]. PMID- 17335735 TI - [Value of the ankle-brachial index in cardiovascular risk stratification of patients without known atherotrombotic disease. MERITO study]. AB - BACKGROUND AND OBJECTIVES: Peripheral arterial disease detected by measurement of ankle-brachial index enables the identification of asymptomatic patients with target organ damage. We have investigated the prevalence of peripheral arterial disease (ankle-brachial index < 0.9), and its potential clinical-therapeutic impact, in patients without known atherotrombotic disease from internal medicine practices. PATIENTS AND METHOD: It was a multicenter, cross-sectional, observational study. Outpatients aged 50 through 80 years, with either diabetes or a SCORE risk estimation of at least 3%, were enrolled. RESULTS: A total of 1,519 subjects (58% men) were evaluated, 917 with diabetes (61%). The mean age (standard deviation) was 66.2 (8.3) years. The prevalence of an ankle-brachial index < 0.9 was 26.19%. In multiple logistic regressions the risk factors associated to an ankle-brachial index < 0.9 were age, sedentary lifestyle, smoking, macroalbuminuria, and heart rate. There was a significant relationship between the ankle-brachial index and the SCORE risk estimation. With respect to the therapeutic aims of the patients with an ankle-brachial index < 0.9, only 21% were taking antiplatelet drugs, 26% showed low density lipoproteins-cholesterol values < 100 mg/dl (53% < 130 mg/dl), and 16% displayed recommended blood pressure levels. CONCLUSIONS: Measurement of ankle-brachial is useful to reclassify as high risk a significant proportion of patients without known previous atherotrombotic disease. The ankle-brachial index should be incorporated into routine cardiovascular evaluation, particularly in subjects with diabetes or a score risk assessment > or = 3%. PMID- 17335736 TI - [Design and early results of a proactive telephone-based smoking cessation treatment compared with face-to-face group sessions]. AB - BACKGROUND AND OBJECTIVE: To assess an intensive proactive telephone smoking cessation program and compare it with a similar group in face to face treatment. DESIGN: A prospective, controlled, observational study performed during daily clinical practice. PATIENTS AND METHOD: PARTICIPANTS: 383 smokers, 176 in telephone treatment and 207 in face to face group treatment, aged greater than 18 years old. They smoked more than 10 cigarettes per day and both groups were recruited between April and November 2003. The study was performed between April 2003 and May 2004. Treatment technique: 11 congnitive-behavioral interventions for six months plus 24 hour nicotine patches in standard doses and 2 mg nicotine gum on demand. Main variable: Prolonged abstinence self-professed at 24 hours, 1 week, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 12, weeks, 16 weeks, 20 weeks and 24 weeks. RESULTS: In the first and second week, abstinence was significantly higher in the face to face group than in telephone treatment (1st. week 80.2% vs. 65.9% p = .001; 2nd. week 77.3% vs 65.3% p = .007). Subsequently, the difference was not significant, and at 24 weeks abstinence remained similar for the two treatment methods, 54.6% in the face to face group treatment and 54.5% in telephone treatment. CONCLUSIONS: Intensive smoking cessation treatment programs, with nicotine replacement therapy, are equally effective if performed by proactive telephone or in face to face treatment sessions. PMID- 17335737 TI - [Factors associated with revisit and admission in patients complaining of fever that are discharged from the emergency department]. AB - BACKGROUND AND OBJECTIVE: To identify factors associated with both emergency department (ED) revisit, and hospital admission of patients complaining of fever that have previously been seen and discharged from the ED. PATIENTS AND METHOD: From September, 2003 to April, 2004, 300 patients complaining of fever were discharged from the ED. Revisit rate and admission rate were calculated. Factors from the first visit associated with revisit, and revisit and admission were assessed by univariate and multivariate regression analysis. RESULTS: Fifty-one (17%) patients were revisit, 26 (9%) of whom were finally admitted. The independent factors associated with revisit were: age greater than 65 (OR = 1.96; p = 0.01), presence of comorbidity (OR = 3.23; p = 0.01), and C-reactive protein higher than 15 mg/dl (OR = 6.67; p = 0.02). The independent factors associated with revisit and admission were: age greater than 65 (OR = 4.51; p = 0.03), and presence of comorbidity (OR = 3.31; p = 0.01). CONCLUSIONS: One-sixth of patients complaining of fever that are discharged from an ED will be seen again. These patients are also more likely to be admitted if they are older than 65 and have any comorbidity present. PMID- 17335738 TI - [Health results-based medicine: logical and desirable evolution of evidence-based medicine]. PMID- 17335739 TI - [Legal framework for the use of autologous blood and other alternatives to allogenic transfusion]. PMID- 17335740 TI - [Terminal heart failure]. AB - Heart failure (HF) is a cardiovascular disease with a permanent increase in prevalence, incidence and mortality. Current optimal therapies for HF are effective only for slowing, but not stopping, its progression. HF-related mortality is high, even at the time of the disease onset. Approximately 40% of HF attributable deaths will be related to disease progression - however, its course is difficult to predict and therefore identifying patients experiencing the terminal stage of the disease is not correctly done. Most patients and their relatives do not identify HF as a progressive, terminal disease, and this perception also stands among health professionals - in consequence, end-stage HF patients often undergo active treatment procedures, event near the occurrence of death, although its implementation will be occasionally futile. Efforts should be undertaken by all health professionals to improve the identification and management of HF patients in the terminal stage of their disease. PMID- 17335741 TI - [Blood cyclosporine analysis through the concentration 2 h after dosis administration]. PMID- 17335742 TI - [Methemoglobinemia due to foodbound agents]. PMID- 17335743 TI - [How long is it necessary to begin a multicentric clinical trial in Spain?]. PMID- 17335744 TI - [Thrombotic thrombocytopenic purpura during treatment with interpheron]. PMID- 17335745 TI - [Recurrent syncopes secondary to pheochromocytoma]. PMID- 17335746 TI - [Cerebral saltwasting syndrome due to infectious diseases of the central nervous system]. PMID- 17335747 TI - [Inclusion-body myositis associated with systemic sclerosis]. PMID- 17335748 TI - [Dutasteride-induced gynecomastia]. PMID- 17335749 TI - [Silicosis]. PMID- 17335765 TI - Specific antibody detection in serum, urine and saliva samples for the diagnosis of cystic echinococcosis. AB - Serum, saliva and urine samples of 25 clinically and radiologically diagnosed cystic echinoccosis (CE) patients, 25 clinically suspected cases of CE, 15 other parasitic disease controls and 25 healthy controls were evaluated for anti hydatid antibody response by ELISA. The sensitivity of serum, saliva and urine was found to be 72, 56 and 84%, respectively, while specificity was 76% in all the samples. Urine showed significantly higher (p<0.05) sensitivity than that of saliva samples but not significantly higher (p>0.05) than that of serum samples. There was no significant difference in the immune response of patients with hepatic versus extrahepatic cysts and single versus multiple cysts. Thus, biological fluid like urine may be used as an alternative or as an adjunct to serum samples by virtue of its non-invasive, easy collection and similar sensitivity and specificity. PMID- 17335766 TI - Anatomic success of lens-sparing vitrectomy with and without scleral buckle for stage 4 retinopathy of prematurity. AB - PURPOSE: To compare the anatomic outcomes of lens-sparing vitrectomy (LSV) with those of combined LSV and scleral buckle (SB) in surgical repair of retinopathy of prematurity (ROP) stage 4 retinal detachment. DESIGN: Retrospective, interventional, consecutive case series. METHODS: Twenty-one eyes of 15 patients with stage 4 ROP detachment were enrolled. All patients were selected from consecutive patients with stage 4 ROP detachment treated with LSV alone or combined LSV and SB. Patient characteristics, including gestational age, birth weight, gender, corrected gestational age at time of surgery, surgical procedure, anatomic outcome, ability to fix and follow, and progression of cataract or glaucoma were recorded. RESULTS: Twelve of 21 eyes underwent the combined procedure (LSV with SB), and the remaining nine eyes underwent LSV alone. Eighteen (86%) of 21 eyes achieved retinal reattachment overall, with seven (87%) of eight stage 4B detachments repaired in one surgery. Eleven (85%) of 13 stage 4A detachments were repaired in one surgery. Of the patients in whom treatment failed, two were in the LSV with SB group (2/12; 16%) and one was in the LSV alone group (1/9; 11%). CONCLUSIONS: The data suggest that SB adds little to the success or failure of LSV and therefore is an unnecessary adjunct to LSV for stage 4 ROP. PMID- 17335767 TI - Therapeutic keratoplasty for advanced suppurative keratitis. AB - PURPOSE: To determine indications, therapeutic success, and corneal transplantation techniques for advanced medically uncontrolled infectious keratitis. DESIGN: Retrospective, interventional case series. METHODS: A review of 92 consecutive patients (1991 to 2002) who underwent therapeutic keratoplasty for acute infectious keratitis performed at Singapore National Eye Centre. Causative organism(s) were identified and outcomes were evaluated in terms of infectious cure (therapeutic success), graft clarity, and visual acuity. RESULTS: Pseudomonas aeruginosa (58.7%) and Fusarium species (32.3%) were the predominant organisms for bacterial and fungal keratitis, respectively. Keratoplasty types included penetrating keratoplasty (PK; n = 80) and lamellar keratoplasty (n = 12). Mean graft diameter was 9.5 mm (range, 5.5 to 14 mm). Seventy-four patients (80.4%) achieved therapeutic success after one keratoplasty procedure, three patients were cured after a second keratoplasty. Life-table survival analysis computed the one-year therapeutic survival for bacterial and fungal keratitis as 76.6% and 72.4%, respectively (P = .76). The Kaplan-Meier one-year survival rate for PK optical clarity was 72%. Twenty-two patients underwent repeat keratoplasty for various reasons (optical, n = 8; recurrent primary infection, n = 7; perforation or subsequent new infections, n = 7). Of the 15 patients for whom therapy failed, 11 had fungal keratitis. Infection recurrence time was four days to one year. Most recurrences (n = 11) appeared within six weeks after surgery. CONCLUSIONS: Therapeutic keratoplasty may treat severe, refractory infectious keratitis effectively. High cure rates are achievable, although infection recurrence despite prolonged treatment remains a significant problem in fungal keratitis. PMID- 17335768 TI - Cholesterol biosensor based on N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane self-assembled monolayer. AB - Cholesterol oxidase (ChOx) has been covalently immobilized onto two-dimensional self-assembled monolayer (SAM) of N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (AEAPTS) deposited on the indium-tin oxide (ITO) coated glass plates using N ethyl-N'-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS) chemistry. These ChO x/AEAPTS/ITO bioelectrodes are characterized using contact angle (CA) measurements, UV-visible spectroscopy, atomic force microscopy (AFM), electrochemical impedance technique, and Fourier transform infrared (FT-IR) technique. The covalently immobilized ChOx-modified AEAPTS bioelectrodes are used for the estimation of cholesterol in solution using UV-visible technique. These cholesterol sensing bioelectrodes show linearity as 50 to 500 mg/dl for cholesterol solution, detection limit as 25mg/dl, sensitivity as 4.499 x 10(-5) Abs (mg/dl)(-1), K(m) value as 58.137 mg/dl (1.5mM), apparent enzyme activity as 1.81 x 10(-3) U cm(-2), shelf life of approximately 10 weeks, and electrode reusability as 10 times. PMID- 17335769 TI - A rapid, homogeneous, fluorescence polarization binding assay for peroxisome proliferator-activated receptors alpha and gamma using a fluorescein-tagged dual PPARalpha/gamma activator. AB - Peroxisome proliferator-activated receptors (PPARs) and other members of the nuclear hormone receptor family are important drug targets for the treatment of metabolic diseases. PPARalpha and PPARgamma play crucial roles in lipid and glucose metabolism, respectively. Therefore, screening methods that help to rapidly identify activators of these receptors should be of considerable value. A homogeneous fluorescence polarization (FP) ligand binding assay capable of rapidly identifying ligands that bind to both PPARalpha and PPARgamma has been developed using purified PPARalpha or PPARgamma ligand binding domains and a fluorescein-labeled analog (FLA) of a potent dual PPARalpha/gamma activator. FLA activator showed good binding affinity toward both PPARalpha (K(i)=0.7microM) and PPARgamma (K(i)=0.4microM). The binding of FLA activator was rapid and reached a plateau within 10 min. The resulting FP signal was stable for at least 18h. The FP binding assay performed robustly in a 384-well format, and the average Z' value was 0.77. There was a good correlation between the binding potency (IC(50) values) and rank order of binding potency for a panel of standard PPAR ligands obtained in FP binding assay and scintillation proximity assay or gel filtration binding assays using (3)H-labeled PPARalpha (r(2)=0.99) and PPARgamma (r(2)=0.99) ligands. There was also a good correlation of IC(50) values obtained by FP binding assay and scintillation proximity assay for the clinically used PPAR activators. Thus, the FP binding assay with a single fluorescein-labeled PPARalpha/gamma dual activator offers a homogeneous nonradioactive, sensitive, robust, and less expensive high-throughput assay for detecting compounds that bind to both PPARgamma and PPARalpha. Using this FP binding assay, we have identified a large number of PPARalpha/gamma dual activators. A similar assay platform may be easily adapted to other members of the nuclear hormone receptor family. PMID- 17335772 TI - Double mutant P96S/S120G of Nm23-H1 abrogates its NDPK activity and motility suppressive ability. AB - The Nm23-H1 gene is a metastasis suppressor gene. However, its biochemical mechanism of suppressing the metastatic potential of cancer cells is still unknown. The previous hypothesis that a histidine protein kinase activity may contributes to the motility-suppressive effect of Nm23-H1 could not explain why the H118F mutant, a kinase-deficient mutant, still had motility-suppressive ability. We conducted a study on the double mutant P96S/S120G of Nm23-H1 and succeeded in introducing the RP-HPLC method in NDPK assay. The results showed that the double mutant P96S/S120G, when expressed in the bacteria, was completely aggregated in inclusion bodies; this mutant abrogated not only its motility suppressive ability, but also its NDPK activity. Based on previous work and this study, we prompted that the deficiency of motility-suppressive function of S120G, P96S, and P96S/S120G mutants was due to their altered structure, which might deprive Nm23-H1 of most activities including kinase activity or interactions with other proteins. PMID- 17335773 TI - Rapid hematopoietic progenitor mobilization by sulfated colominic acid. AB - Hematopoietic progenitor cells (HPCs) can be mobilized from bone marrow (BM) to the blood by G-CSF. In this process, CXCR4 and CD26 play critical roles. Sulfated colominic acid (SCA) inhibits HIV entry, the step which requires CXCR4 and CD26 as co-receptors. Thus, we hypothesized that SCA would modulate HPC trafficking. We first found that SCA mobilized HPCs rapidly via CD26-independent mechanism. In vitro progenitor migration toward chemokine SDF-1 was significantly enhanced by SCA, and it was completely abrogated by CXCR4 inhibition. This likely originated from the inhibition of CXCR4 down-regulation after interaction with SDF-1. Serum SDF-1 level increased after SCA injection, whereas no change was observed in BM and bone. These results suggest that SCA induces HPC mobilization by modulating CXCR4 function resulting in attraction toward increased SDF-1 in the circulation. Furthermore, we confirmed an additive effect with G-CSF in mobilization. SCA may provide an efficacy in clinical mobilization. PMID- 17335774 TI - Critical role of cholesterol ester transfer protein in nicotinic acid-mediated HDL elevation in mice. AB - Nicotinic acid is a commonly used anti-dyslipidemic agent that increases plasma levels of HDL-cholesterol and decrease triglycerides (TG), and VLDL- and LDL cholesterol. The most well-studied effect of nicotinic acid is its ability to lower plasma free fatty acids, which has been observed in humans and many animal models. However, its ability to raise HDL in humans has not been replicated in animal models, which precludes studying the mechanism of HDL elevation. Here we studied lipid-modulating effects of nicotinic acid in mice carrying genomic DNA fragments that drive expression of various human genes in the mouse liver. Treatment with nicotinic acid reduced serum levels of HDL cholesterol in wild type and human apolipoprotein B100 (apoB100)-transgenic mice. In contrast, nicotinic acid treatment of mice that express human cholesteryl ester transfer protein (CETP), with or without concomitant apoB100 expression, resulted in a significant increase of HDL cholesterol and reduction of TG, VLDL- and LDL cholesterol. These data demonstrate a critical role of CETP in nicotinic acid mediated HDL elevation, and suggest that mice carrying the human CETP gene may be useful animal models for studying the HDL-elevating effect of nicotinic acid. PMID- 17335775 TI - Production of an active feline interferon in the cocoon of transgenic silkworms using the fibroin H-chain expression system. AB - We constructed the fibroin H-chain expression system to produce recombinant proteins in the cocoon of transgenic silkworms. Feline interferon (FeIFN) was used for production and to assess the quality of the product. Two types of FeIFN fusion protein, each with N- and C-terminal sequences of the fibroin H-chain, were designed to be secreted into the lumen of the posterior silk glands. The expression of the FeIFN/H-chain fusion gene was regulated by the fibroin H-chain promoter domain. The transgenic silkworms introduced these constructs with the piggyBac transposon-derived vector, which produced the normal sized cocoons containing each FeIFN/H-chain fusion protein. Although the native-protein produced by transgenic silkworms have almost no antiviral activity, the proteins after the treatment with PreScission protease to eliminate fibroin H-chain derived N- and C-terminal sequences from the products, had very high antiviral activity. This H-chain expression system, using transgenic silkworms, could be an alternative method to produce an active recombinant protein and silk-based biomaterials. PMID- 17335776 TI - Immobilization and activity assay of cytochrome P450 on patterned lipid membranes. AB - We report on a methodology for immobilizing cytochrome P450 on the surface of micropatterned lipid bilayer membranes and measuring the enzymatic activity. The patterned bilayer comprised a matrix of polymeric lipid bilayers and embedded fluid lipid bilayers. The polymeric lipid bilayer domains act as a barrier to confine fluid lipid bilayers in defined areas and as a framework to stabilize embedded membranes. The fluid bilayer domains, on the other hand, can contain lipid compositions that facilitate the fusion between lipid membranes, and are intended to be used as the binding agent of microsomes containing rat CYP1A1. By optimizing the membrane compositions of the fluid bilayers, we could selectively immobilize microsomal membranes on these domains. The enzymatic activity was significantly higher on lipid bilayer substrates compared with direct adsorption on glass. Furthermore, competitive assay experiment between two fluorogenic substrates demonstrated the feasibility of bioassays based on immobilized P450s. PMID- 17335777 TI - Characterization of hampin/MSL1 as a node in the nuclear interactome. AB - Hampin, homolog of Drosophila MSL1, is a partner of histone acetyltransferase MYST1/MOF. Functions of these proteins remain poorly understood beyond their participation in chromatin remodeling complex MSL. In order to identify new proteins interacting with hampin, we screened a mouse cDNA library in yeast two hybrid system with mouse hampin as bait and found five high-confidence interactors: MYST1, TPR proteins TTC4 and KIAA0103, NOP17 (homolog of a yeast nucleolar protein), and transcription factor GC BP. Subsequently, all these proteins were used as baits in library screenings and more new interactions were found: tumor suppressor RASSF1C and spliceosome component PRP3 for KIAA0103, ring finger RNF10 for RASSF1C, and RNA polymerase II regulator NELF-C for MYST1. The majority of the observed interactions was confirmed in vitro by pull-down of bacterially expressed proteins. Reconstruction of a fragment of mammalian interactome suggests that hampin may be linked to diverse regulatory processes in the nucleus. PMID- 17335778 TI - Involvement of the calcium channel beta3 subunit in olfactory signal transduction. AB - Despite the expression of voltage-dependent Ca2+ channels in nasal turbinate epithelium, their role in odorant chemosensation has remained obscure. Therefore, we investigated olfactory neurotransduction in beta3-deficient mice. RT-PCR and Western blots confirmed the expression of various types of Ca2+ channels in the nasal turbinate. Electrophysiological evaluations revealed that beta3-null mice had a 60% reduction in the high-voltage-dependent Ca2+ currents in olfactory receptor neurons due to reduced N- and L-type channel currents. The beta3-null mice showed increased olfactory neuronal activity to triethylamine, and this effect was mimicked by the perfusion of the specific N-type Ca2+ channel inhibitor omega-conotoxin GVIA in the electro-olfactogram. Diluted male urine odors induced higher Fos immunoreactivity in the main olfactory bulbs of beta3 deficient mice, indicating enhanced signal transduction of odor information in these mice. Our data indicate the involvement of voltage-dependent Ca2+ channels and importance of the beta3 subunit in olfactory signal transduction. PMID- 17335779 TI - Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates. AB - The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5x10(-3)M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. (45)Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H(2)O(2)-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8m(2) surface area with its calcium gradient in the 10( 3)M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non neuronal tissue. PMID- 17335780 TI - Proteins that bind to the RERMS region of beta amyloid precursor protein. AB - The main objective of this study was to investigate the biological function of beta amyloid precursor protein (APP), in particular its nerve growth factor-like activity. We hypothesize that the extracellular domain containing the sequence RERMS, amino acids 328-332 of APP(695), represents the active site for this function. Binding assays using peptide fragments of this domain have demonstrated specific and saturable binding to the cell surface with affinity in the low nanomolar range. This induced our quest for an APP-specific receptor. We chose different peptide fragments of the RERMS domain as ligands and displacing agents on affinity columns to purify APP-binding molecules. Amino acid microsequencing yielded partial sequences of serum albumin, actin, two novel proteins of 41 and 63kDa, and human Collapsin Response Mediator Protein-2 (hCRMP-2). Because both APP and hCRMP-2 promote neuronal outgrowth and use a common signaling pathway, APP could be acting through a semaphorin receptor as well. PMID- 17335782 TI - Polysialic acid limits septal neurite outgrowth on laminin. AB - Polysialic acid (PSA) is a large carbohydrate found exclusively on the neural cell adhesion molecule (NCAM). In the adult brain, PSA is re-expressed by septal axons sprouting and regenerating in an environment rich in laminin. Using an in vitro model, we tested the possibility that PSA limits septal outgrowth by preventing maximal interactions with a laminin substrate. Our results indicate that PSA removal from primary septal neurons plated on laminin significantly increased neurite outgrowth at 12 h (14%, p<0.05) and 24 h (22%, p<0.01). In contrast, the removal of PSA had no impact on septal neurite outgrowth on poly-D lysine. PSA did not influence the plating adhesion of septal neurons on laminin or poly-D-lysine, indicating that the increase in neurite outgrowth caused by PSA removal on laminin is not related to the initial attachment of the neurons to this substrate. Neurite length on laminin was significantly reduced by the function-blocking beta1-integrin antibody in the presence of PSA (20% decrease, p<0.05), and following PSA removal (34% decrease compared to neurites treated with endoN and without the beta1-integrin antibody, p<0.01). Importantly, the beta1-integrin antibody completely abolished the neurite outgrowth promoting effect of PSA removal on laminin. The beta1-integrin antibody had no impact on septal neurite length on poly-D-lysine. Taken together, these results indicate that the removal of PSA from septal neurons increases neurite outgrowth on laminin by promoting interactions between beta1-integrin and laminin. PMID- 17335781 TI - Chronic administration of methylphenidate produces neurophysiological and behavioral sensitization. AB - The electrophysiological properties of acute and chronic methylphenidate (MPD) on neurons of the prefrontal cortex (PFC) and caudate nucleus (CN) have not been studied in awake, freely behaving animals. The present study was designed to investigate the dose-response effects of MPD on sensory evoked potentials recorded from the PFC and CN in freely behaving rats previously implanted with permanent electrodes, as well as their behavioral (locomotor) activities. On experimental day 1, locomotor behavior of rats was recorded for 2 h post-saline injection, and sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10 mg/kg, i.p., MPD administration. Animals were injected for the next five days with daily 2.5 mg/kg MPD to elicit behavioral sensitization. Locomotor recording was resumed on experimental days 2 and 6 after the MPD maintenance dose followed by 3 days of washout. On experimental day 10, rats were connected again to the electrophysiological recording system and rechallenged with saline and the identical MPD doses as on experimental day 1. On experimental day 11, rat's locomotor recording was resumed before and after 2.5 mg/kg MPD administration. Behavioral results showed that repeated administration of MPD induced behavioral sensitization. Challenge doses (0.6, 2.5, and 10.0 mg/kg) of MPD on experimental day 1 elicited dose-response attenuation in the response amplitude of the average sensory evoked field potential components recorded from the PFC and CN. Chronic MPD administration resulted in attenuation of the PFC's baseline recorded on experimental day 10, while the same treatment did not modulate the baseline recorded from the CN. Treatment of MPD on experimental day 10 resulted in further decrease of the average sensory evoked response compared to that obtained on experimental day 1. This observation of further decrease in the electrophysiological responses after chronic administration of MPD suggests that the sensory evoked responses on experimental day 10 represent neurophysiological sensitization. Moreover, two different response patterns were obtained from PFC and CN following chronic methylphenidate administration. In PFC, the baseline and effect of methylphenidate expressed electrophysiological sensitization on experimental day 10, while recording from CN did not exhibit any electrophysiological sensitization. PMID- 17335784 TI - Polymorphisms of cholesterol metabolism genes CYP46 and ABCA1 and the risk of sporadic Alzheimer's disease in Chinese. AB - Recent studies have demonstrated that cholesterol metabolism might play an important role in Alzheimer's disease (AD). Cholesterol 24-hydroxylase (CYP46) and ATP-binding cassette transporter A1 (ABCA1) have both been proposed to be involved in cholesterol metabolism in the brain. The purpose of this case-control study was to determine whether single nucleotide polymorphisms (SNPs) A-->G in the intron 2 of CYP46 gene and G-->A (R219K) in the exon 7 of ABCA1 gene are associated with sporadic AD in the Chinese Han population. Genotypes were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) in 168 sporadic AD patients and 215 controls. There was no significant difference in the genotype or allele frequencies for CYP46 gene between AD patients and controls. However, we found an obvious association between the polymorphism of ABCA1 gene and AD (chi(2)=8.230, P=0.016). The risk for AD was significantly decreased in K allele (RK+KK genotypes) (adjusted OR=0.57, 95% CI=0.36-0.91, P=0.019) or KK homozygote carriers (adjusted OR=0.40; 95% CI=0.21-0.77, P=0.006) compared with RR genotypes carriers. Our results do not support a genetic association between the intron 2 polymorphism of CYP46 gene and the risk of sporadic AD, but reveal that KK genotype or K allele of ABCA1 gene may have a protective effect for sporadic AD in Chinese. PMID- 17335783 TI - Local-global interference is modulated by age, sex and anterior corpus callosum size. AB - To identify attentional and neural mechanisms affecting global and local feature extraction, we devised a global-local hierarchical letter paradigm to test the hypothesis that aging reduces functional cerebral lateralization through corpus callosum (CC) degradation. Participants (37 men and women, 26-79 years) performed a task requiring global, local, or global+local attention and underwent structural MRI for CC measurement. Although reaction time (RT) slowed with age, all participants had faster RTs to local than global targets. This local precedence effect together with greater interference from incongruent local information and greater response conflict from local targets each correlated with older age and smaller callosal genu (anterior) areas. These findings support the hypothesis that the CC mediates lateralized local-global processes by inhibition of task-irrelevant information under selective attention conditions. Further, with advancing age smaller genu size leads to less robust inhibition, thereby reducing cerebral lateralization and permitting interference to influence processing. Sex was an additional modifier of interference, in that callosum interference relationships were evident in women but not in men. Regardless of age, smaller splenium (posterior) areas correlated with less response facilitation from repetition priming of global targets in men, but with greater response facilitation from repetition priming of local targets in women. Our data indicate the following dissociation: anterior callosal structure was associated with inhibitory processes (i.e., interference from incongruency and response conflict), which are vulnerable to the effects of age and sex, whereas posterior callosal structure was associated with facilitation processes from repetition priming dependent on sex and independent of age. PMID- 17335785 TI - Long lasting sex-specific effects upon behavior and S100b levels after maternal separation and exposure to a model of post-traumatic stress disorder in rats. AB - This study was undertaken to verify if repeated long-term separation from dams would affect the development of parameters related to post-traumatic stress disorder (PTSD) after animals are subjected to inescapable shock when adults. Wistar rats were subjected to repeated maternal separation during post-natal days 1-10. When adults, rats from both sexes were submitted to a PTSD model consisting of exposure to inescapable footshock, followed by situational reminders. We observed long-lasting effects of both interventions. Exposure to shock increased fear conditioning. Anxiety-like behavior was increased and exploratory activity decreased by both treatments, and these effects were more robust in males. Additionally, basal corticosterone in plasma was decreased, paralleling effects observed in PTSD patients. Levels of S100B protein in serum and cerebrospinal fluid (CSF) were measured. Levels in serum correlated with the effects observed in anxiety-like behavior, increasing in males exposed to shock, and presenting no effect in females. S100B in CSF was increased in females submitted to maternal separation during the neonatal period. These results suggest that, in rats, an early stress experience such as maternal separation may aggravate some effects of exposure to a stressor during adult age, and that this effect is sex-specific. Additionally, data suggest that the increased S100B levels, observed in serum, have an extracerebral origin, possibly mediated by an increase in the noradrenergic tonus. Increased S100B in brain could be related to its neurotrophic actions. PMID- 17335786 TI - The effect of infusing hypoxanthine or xanthine on hypoxic-ischemic brain injury in rabbits. AB - Xanthine oxidase (XO), an enzyme that converts hypoxanthine to xanthine and xanthine to uric acid, is thought to contribute to hypoxic-ischemic brain injury by generating oxygen-free radicals during reperfusion. This is based largely on the observation that inhibition of XO reduces brain damage, but the precise mechanism by which the enzyme contributes to cerebral ischemic injury has not been specifically evaluated. We examined the role of XO in generating oxygen-free radicals that cause brain injury, hypothesizing that if XO generated a significant amount of free radicals during hypoxia-ischemia and reperfusion, providing additional substrate at the time of injury should increase brain damage. Anesthetized rabbits were first subjected to 8 min of cerebral hypoxia by breathing 3% oxygen and then to 8 min of ischemia by raising intracranial pressure equal to mean arterial pressure with an artificial CSF. In order to promote oxygen-free radical generation, hypoxanthine (n=9) or xanthine (n=9), XO substrates, or the vehicle (n=8) was infused intravenously beginning 30 min before and continuing until 30 min after the insult. Animals were sacrificed after 4 h of reperfusion. Neither hypoxanthine nor xanthine infusion increased brain damage. However, administration of hypoxanthine significantly improved somatosensory evoked potential recovery and preserved neurofilament 68 kDa protein, a neuronal structural protein. This study does not support free radical generation by XO as a major cause of damage in cerebral hypoxia-ischemia. Infusion of hypoxanthine reduced cerebral injury suggesting that another mechanism may explain why inhibition of XO reduces brain damage. PMID- 17335787 TI - Desialylation of core type 1 O-glycan in the equine embryonic capsule coincides with immobilization of the conceptus in the uterus. AB - During the second and third weeks of pregnancy, the equine conceptus expands rapidly while it is enclosed within a glycan capsule. Around day 16 of gestation, the conceptus loses its mobility in the uterus by a process termed 'fixation', coinciding with various changes in the capsule. Here, we compared the structure of the carbohydrate moieties expressed by the capsule during pre- and post fixation periods. The glycan structures were studied by chemical analyses in combination with mass spectrometry. Capsule material from conceptuses collected before fixation (days 13-16) was observed to carry a sialylated core type 1 O linked glycan, Neu5Ac-(2-->3)-Gal-(1-->3)-GalNAc-(1-->Ser/Thr. By comparison, analysis of post-fixation capsules (days 17-19) revealed a desialylated core type 1, Gal-(1-->3)-GalNAc-(1-->Ser/Thr. The equine embryonic capsule also furnished 4 substituted GlcNAc, 4-substituted Glc and 2,3,4,6-tetrasubstituted Glc residues, the concentrations of which did not change between pre- and post-fixation stages. The loss of sialic acid from the sialylated core type 1 in the capsule appears to be directly related to successful fixation of the conceptus, and thus critical to the continuance of pregnancy in horses. PMID- 17335788 TI - The behaviour of deoxyhexose trihaloacetimidates in selected glycosylations. AB - Armed deoxyhexose glycosyl donors are very reactive and sometimes too uncontrollably activated in glycosylation reactions; yields can be thereby reduced, especially when unreactive glycosyl acceptors are involved. In this paper, the behaviour of a range of deoxyhexose trihaloacetimidate (trichloro- and N-phenyl trifluoro-) donors is compared in some selected glycosylations towards biologically relevant targets. The selected N-phenyl trifluoroacetimidates often afforded best results in terms of both donor synthesis and glycosylation yield. PMID- 17335789 TI - Additive effect of interleukin-6 and C-reactive protein (CRP) single nucleotide polymorphism on serum CRP concentration and other cardiovascular risk factors. AB - BACKGROUND: Serum C-reactive protein (CRP) levels, closely associated with cardiovascular disease (CVD) risk are influenced by CRP or interleukin-6 (IL-6) single nucleotide polymorphism (SNPs). However, it is still controversial. Therefore, we investigated the association of IL-6/CRP SNPs and serum CRP levels or other CVD risk factors in healthy adult Korean men. METHODS: In healthy adult men (age>or=20 years, n=677), we genotyped IL-6-572C>G and CRP SNPs (-717G>A, 1444C>T, 2147A>G) and measured anthropometric parameters, lipid profile, serum levels of CRP and IL-6 and insulin resistance. RESULTS: At IL-6-572C>G (n=677), subjects with G/G genotype (n=42) showed higher concentrations of CRP (P=0.027) and IL-6 (P=0.028) as compared with C allele carriers after age-adjustment (C/C: n=371, C/G: n=264). Fasting insulin and homeostatis model assessment insulin resistance (HOMA-IR) were also higher in G/G genotype. However, there were no significant differences in other metabolic biomarkers. Among 677 study subjects, 676 were genotyped at CRP-717G>A (G/G: n=513, G/A: n=150, A/A: n=13), 672 at CRP+1444C>T (C/C: n=580, C/T: n=85, T/T: n=7), and 668 at CRP+2147A>G (A/A: n=273, A/G: n=296, G/G: n=99). There were no significant differences in CRP concentrations and other markers related to CVD risk according to each CRP SNP genotype. However, we could find the additive gene-gene interaction between IL-6 572C>G and CRP SNPs on CRP concentration; subjects with the 'G/G' at IL-6-572 showed the highest CRP levels when they have variant allele at CRP SNPs after adjusted for age, body mass index, cigarette smoking and alcohol drinking ( 717G>A: F=7.806, P=0.005; CRP+1444C>T: F=8.398, P=0.004; and CRP+2147A>G: F=7.564, P=0.006, respectively) Particularly, G allele carriers at CRP+2147A>G in subjects with IL-6-572G/G showed highest HOMA-IR (F=9.092, P=0.003). CONCLUSION: The present data showed that serum CRP levels and other CVD risk factors appeared more influenced by IL-6-572C>G rather than CRP SNPs (-717G>A, 1444C>T, and 2147A>G), however CRP levels and insulin resistance may be additively affected by IL-6-572 and CRP SNP, particularly when subjects with G/G genotype at IL-6-572 have allele variant at CRP SNPs. PMID- 17335790 TI - Inter- and intra-individual variations in normal urinary glycine betaine excretion. AB - OBJECTIVES: To establish whether normal human subjects excrete glycine betaine at a constant rate. DESIGN AND METHODS: Urine was collected from ten normal healthy male subjects for 14 days, during which fluid intake was systematically varied from <800 mL to >3 L per day. Glycine betaine, sorbitol and creatinine excretions were estimated per day and as millimole per mol creatinine. RESULTS: The intrasubject SD of urine glycine betaine was 3.5 mmol/mol creatinine, and the intersubject SD 5.8 mmol/mol creatinine. The intrasubject SD of plasma glycine betaine was 10.2 mol/L and the intersubject SD 14.2 mol/L. Water load had little effect on glycine betaine excretion and plasma glycine betaine. After 12 years, excretions and plasma concentrations tended to parallel the initial results. CONCLUSIONS: Normal subjects have consistent individual glycine betaine excretions that are not strongly influenced by urine volume. Abnormal excretions, or significant changes in excretion, can be interpreted as indicating a pathological process. PMID- 17335791 TI - Serum paraoxonase-1 in chronic alcoholics: relationship with liver disease. AB - OBJECTIVES: To investigate the relationship between serum paraoxonase-1 and liver damage in chronic alcoholic patients. To assess the diagnostic accuracy of paraoxonase-1 plus standard biochemical tests in the assessment of liver damage in alcoholics. DESIGN AND METHODS: We studied 328 chronic alcoholics and 368 healthy individuals. RESULTS: Paraoxonase-1 activity was decreased and the concentration was increased in alcoholics (P<0.001). The enzyme activity was correlated with albumin (r=0.45; P<0.001) and prothrombin time (r=0.49; P<0.001). Addition of paraoxonase-1 activity measurement to a battery of biochemical tests increased the sensitivity in differentiating between patients and controls up to 96.6% but did not improve the sensitivity in differentiating between subgroups of alcoholics. CONCLUSIONS: Paraoxonase-1 was related to the severity of alcoholic liver disease. Its measurement was useful in discriminating between patients and healthy subjects, but did not add any valuable information in subgroups of alcoholics. PMID- 17335792 TI - PON1 status in haemodialysis patients and the impact of hepatitis C infection. AB - OBJECTIVES: Paraoxonase-1 (PON1) activity has been reported to decrease in both haemodialysis patients and patients with HCV infection. We aimed to investigate paraoxonase and arylesterase activities, and lipid hydroperoxide levels (LOOH) in haemodialysis patients with or without hepatitis C infection, and to find out whether PON1 activity is affected further by the presence of HCV infection in HD patients. DESIGN AND METHODS: Twenty HCV (+) haemodialysis patients, 26 HCV (-) haemodialysis patients, and 26 controls were enrolled. Paraoxonase and arylesterase activities were measured spectrophotometrically. LOOH levels were measured by ferrous oxidation with xylenol orange assay. RESULTS: Haemodialysis patients with or without HCV infection had lower paraoxonase and arylesterase activities than controls (all p<0.001), while higher LOOH levels (both p<0.001). Paraoxonase and arylesterase activities, and LOOH levels were comparable between haemodialysis patients with or without HCV infection (p>0.05). Significant inverse correlation was observed between paraoxonase or arylesterase activities, and LOOH levels (p<0.05, beta=-0.319 and p<0.05, beta=-0.348, respectively). CONCLUSION: We concluded that PON1 activity significantly decreases in both haemodialysis patients with or without HCV infection. Nevertheless, PON1 activity is not affected further by the presence of HCV infection in haemodialysis patients. PMID- 17335793 TI - Children prefer certain individuals over perfect duplicates. AB - Adults value certain unique individuals--such as artwork, sentimental possessions, and memorabilia--more than perfect duplicates. Here we explore the origins of this bias in young children, by using a conjurer's illusion where we appear to produce identical copies of real-world objects. In Study 1, young children were less likely to accept an identical replacement for an attachment object than for a favorite toy. In Study 2, children often valued a personal possession of Queen Elizabeth II more than an identical copy, but showed no such bias for another sort of valuable object. These findings suggest that young children develop attachments to individuals that are independent of any perceptible properties that the individuals possess. PMID- 17335794 TI - Wnt3a regulates Lef-1 expression during airway submucosal gland morphogenesis. AB - Regulation of the lymphoid enhancer factor 1 (Lef-1) transcription factor is important for the inductive formation of many epithelial-derived appendages including airway submucosal glands (SMGs). Although Wnts have been linked to developmental processes involving transcriptional activation of the Lef-1 protein, there is little in vivo information directly linking Wnts with the transcriptional regulation of the Lef-1 promoter. In the present study, we hypothesized that Wnt3a directly regulates Lef-1 gene expression required for SMG morphogenesis in mice. In support of this hypothesis, TOPGAL reporter mice demonstrated activation of beta-catenin/Tcf complexes during early phases of SMG development and immunolocalization studies confirmed abundant expression of Tcf4, but not Tcf1 or Tcf3, at this stage. ChIP analysis in primary airway epithelial cells revealed that Tcf4 associates with a known Wnt Responsive Region in the Lef 1 promoter and transfection of Cos-1 cells with dominant active beta-catenin and Tcf4 synergistically activated the Lef-1 promoter. Using Wnt3a deficient and Lef 1 promoter-GFP reporter mice, we also demonstrate that Wnt3a induces Lef-1 gene expression in newly forming SMG buds of mice and is required for the maintenance of gland bud growth. These findings provide the first in vivo evidence that Wnt3a can transcriptionally regulate the Lef-1 gene. PMID- 17335795 TI - Function and regulation of zebrafish nkx2.2a during development of pancreatic islet and ducts. AB - In the mouse Nkx2.2 is expressed in the entire pancreatic anlage. Nevertheless, absence of Nkx2.2 only perturbs the development of endocrine cell types, notably beta-cells which are completely absent. In order to test the possibility that Nkx2.2 might fulfil additional functions during pancreas development we analysed its zebrafish homologue nkx2.2a using gene targeting and GFP-transgenic fish lines. Our results suggest similar roles for nkx2.2a and Nkx2.2 during the development of the endocrine pancreas. Morpholino-based knock-down of nkx2.2a leads to a reduction of alpha- and beta-cell number and an increase of ghrelin producing cells but, as in mice, does not affect delta-cells. Moreover, like in the mouse, two spatially distinct promoters regulate expression of nkx2.2a in precursors and differentiated islet cells. In addition we found that in zebrafish nkx2.2a is also expressed in the anterior pancreatic bud and, later, in the differentiated pancreatic ducts. A nkx2.2a-transgenic line in which pancreatic GFP expression is restricted to the pancreatic ducts revealed that single GFP positive cells leave the anterior pancreatic bud and move towards the islet where they form intercellular connections between each other. Subsequently, these cells generate the branched network of the larval pancreatic ducts. Morpholinos that block nkx2.2a function also lead to the absence of the pancreatic ducts. We observed the same phenotype in ptf1a-morphants that are additionally characterized by a reduced number of nkx2.2a-positive duct precursors. Whereas important details of the molecular program leading to the differentiation of endocrine cell types are conserved between mammals and zebrafish, our results reveal a new function for nkx2.2a in the development of the pancreatic ducts. PMID- 17335796 TI - Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme. AB - Craniofacial bones derive from cephalic neural crest, by endochondral or intramembranous ossification. Here, we address the role of the homeobox transcription factor Dlx5 during the initial steps of calvaria membranous differentiation and we show that Dlx5 elicits Runx2 induction and full osteoblast differentiation in embryonic suture mesenchyme grown "in vitro". First, we compare Dlx5 expression to bone-related gene expression in the developing skull and mandibular bones. We classify genes into three groups related to consecutive steps of ossification. Secondly, we study Dlx5 activity in osteoblast precursors, by transfecting Dlx5 into skull mesenchyme dissected prior to the onset of either Dlx5 and Runx2 expression or osteogenesis. We find that Dlx5 does not modify the proliferation rate or the expression of suture markers in the immature calvaria cells. Rather, Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis "in vivo". Thirdly, we show that BMP signaling activates Dlx5, Runx2, and alkaline phosphatase in those primary cultures and that a dominant-negative Dlx factor interferes with the ability of the BMP pathway to activate Runx2 expression. Together, these data suggest a pivotal role of Dlx5 and related Dlx factors in the onset of differentiation of chick calvaria osteoblasts. PMID- 17335799 TI - The role of gender and sex hormones in ischemic-reperfusion injury in isolated rat hearts. AB - To establish potential anti-ischemic effects of testosterone and estradiol on myocardium we used isolated rat hearts in accordance with Langendorff, exposed to 40 min of ischemia and reperfusion. Rats were pretreated for 10 days, males with testosterone and females with estradiol and injuries from those hearts were compared to the hearts where both drugs were applied to the isolated hearts directly. The myocardial injuries were determined by changes in coronary flow, incidence and duration of arrhythmias and lactate dehydrogenase release rates used as markers for level of cardiac injury during reperfusion. Coronary flow in the hearts of animals pretreated with estradiol during reperfusion increased by 68.7+/-3.6% (P<0.001) and in those pretreated with testosterone by 50.1+/-2.1% (P<0.05) vs. control hearts. Lactate dehydrogenase release rates decreased in the hearts of animals pretreated with estradiol by 55.7+/-1.9% (P<0.01) vs. controls and by 58.8+/-3.0 (P<0.01) vs. directly applied estradiol. Duration of ventricular fibrillation decreased after 10 days application of drugs, from 9.42+/-0.81 min to 4.58+/-0.93 min (P<0.05) with estradiol and from 9.19+/-1.05 min to 4.65+/-0.51 min (P<0.05) with testosterone. The duration of heart arrest decreased in 10 days application of testosterone from 2.42+/-0.16 min to 20.0+/ 12.26 s (P<0.01). Hearts from animals pretreated for 10 days with estradiol showed more cardioprotective effects during reperfusion than those pretreated with testosterone. Testosterone pretreatment, despite being less effective in cardioprotection than estradiol, improved coronary flow and decreased arrhythmias as effectively as estradiol. PMID- 17335798 TI - Transactivation from Gal4-VP16 transgenic insertions for tissue-specific cell labeling and ablation in zebrafish. AB - Prior studies with transgenic zebrafish confirmed the functionality of the transcription factor Gal4 to drive expression of other genes under the regulation of upstream activator sequences (UAS). However, widespread application of this powerful binary system has been limited, in part, by relatively inefficient techniques for establishing transgenic zebrafish and by the inadequacy of Gal4 to effect high levels of expression from UAS-regulated genes. We have used the Tol2 transposition system to distribute a self-reporting gene/enhancer trap vector efficiently throughout the zebrafish genome. The vector uses the potent, hybrid transcription factor Gal4-VP16 to activate expression from a UAS:eGFP reporter cassette. In a pilot screen, stable transgenic lines were established that express eGFP in reproducible patterns encompassing a wide variety of tissues, including the brain, spinal cord, retina, notochord, cranial skeleton and muscle, and can transactivate other UAS-regulated genes. We demonstrate the utility of this approach to track Gal4-VP16 expressing migratory cells in UAS:Kaede transgenic fish, and to induce tissue-specific cell death using a bacterial nitroreductase gene under UAS control. The Tol2-mediated gene/enhancer trapping system together with UAS transgenic lines provides valuable tools for regulated gene expression and for targeted labeling and ablation of specific cell types and tissues during early zebrafish development. PMID- 17335797 TI - Molecular mechanisms of optic vesicle development: complexities, ambiguities and controversies. AB - Optic vesicle formation, transformation into an optic cup and integration with neighboring tissues are essential for normal eye formation, and involve the coordinated occurrence of complex cellular and molecular events. Perhaps not surprisingly, these complex phenomena have provided fertile ground for controversial and even contradictory results and conclusions. After presenting an overview of current knowledge of optic vesicle development, we will address conceptual and methodological issues that complicate research in this field. This will be done through a review of the pertinent literature, as well as by drawing on our own experience, gathered through recent studies of both intra- and extra cellular regulation of optic vesicle development and patterning. Finally, and without attempting to be exhaustive, we will point out some important aspects of optic vesicle development that have not yet received enough attention. PMID- 17335800 TI - dextro-Morphine attenuates the morphine-produced conditioned place preference via the sigma(1) receptor activation in the rat. AB - An unbiased conditioned place preference paradigm was used to evaluate the effect of dextro-morphine on the morphine-produced reward in male CD rats. Morphine sulfate (1-10 mg/kg) given intraperitoneally dose-dependently produced the conditioned place preference. Pretreatment with dextro-morphine at a dose from 0.1 to 3 microg/kg given subcutaneously dose-dependently attenuated the morphine produced conditioned place preference. However, dextro-morphine at a higher dose 100 microg/kg did not affect the morphine-produced conditioned place preference. Thus, dextro-morphine pretreatment induces a U-shaped dose-response curve for attenuating the morphine-produced conditioned place preference. The attenuation of the morphine-produced conditioned place preference was reversed by the pretreatment with the sigma(1) receptor antagonist BD1047 (N-[2-(3,4 Dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide. dextro Morphine or BD1047 given alone did not affect the baseline place conditioning. It is concluded that dextro-morphine attenuated the morphine-produced conditioned place preference via the sigma(1) receptor activation. PMID- 17335801 TI - Attenuation of contractile dysfunction by atorvastatin after intestinal ischemia reperfusion injury in rats. AB - Growing number of studies implicate that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have beneficial effects on ischemia/reperfusion injury that are unrelated to their cholesterol-lowering action. In the present study, we aimed to evaluate possible effects of atorvastatin on oxidative stress, neutrophil accumulation, and contractile response of terminal ileum segments in rats subjected to intestinal ischemia/reperfusion. Intestinal ischemia/reperfusion model was generated by clamping the superior mesenteric artery for 30 min followed by reperfusion for 3 h. Oral administration of atorvastatin at a dose of 10 mg/kg/day lasted 3 days just before induction of intestinal ischemia. At the end of reperfusion period, terminal ileum samples were removed to determine the concentrations of malondialdehyde, reduced glutathione, and myeloperoxidase. Samples were collected also to assess histopathological alterations and contractile response to agonists. Ischemia/reperfusion significantly decreased contractile responses, and this decrease was attenuated by atorvastatin. Pretreatment with atorvastatin caused remarkable decrease in both oxidative stress and neutrophil accumulation. Atorvastatin appeared to be restoring amount of reduced glutathione back to about control level. Furthermore, the pretreatment lowered mucosal damage at histopathological level. Our results suggested that pretreatment with atorvastatin attenuated intestinal muscle dysfunction associated with ischemia/reperfusion. This remarkable effect of atorvastatin is accomplished at least by decreasing oxidative stress and neutrophil accumulation as well as preventing the depletion of reduced glutathione. PMID- 17335802 TI - Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis. AB - A systemic inflammatory response (SIR) occurs prior to and during the treatment of severe diabetic ketoacidosis (DKA). IL-1beta, TNF-alpha and C5b-9 are components of SIR and have been speculated to be involved in the clinical brain edema (BE) of DKA. We studied IL-1beta, TNF-alpha, C5b-9, inducible nitric oxide (iNOS), ICAM-1, IL-10 and Hsp70 expression in the brains of two patients who died as the result of clinical BE during the treatment of DKA. IL-1beta was strongly expressed in the choroid plexus epithelium (CPE) and ependyma, and to a lesser extent in the hippocampus, caudate, white matter radiation of the pons, molecular layer of the cerebellum and neurons of the cortical gray matter. TNF-alpha was expressed to a lesser extent than IL-1beta, and only in the CP. C5b-9, previously shown to be deposited on neurons and oligodendrocytes, was found on CPE and ependymal cells. iNOS and ICAM-1 had increased expression in the CPE and ependyma. Hsp70 and IL-10 were also expressed in the CPE of the case with the shorter duration of treatment. Our data demonstrate the presence of a multifaceted neuroinflammatory cytotoxic insult of the CPE, which may play a role in the pathophysiology of the fatal brain edema of DKA. PMID- 17335803 TI - Prognostic value of HER2 gene amplification detected by chromogenic in situ hybridization (CISH) in metastatic breast cancer. AB - After so many years of research, clinical value of HER2 (Human epidermal growth factor receptor 2) is unclear. Perhaps the main reason is variability of testing methods that produce controversial results. There is a lack of studies regarding prognostic value of CISH especially in metastatic breast cancer (MBC) when risk evaluation is based on different parameters than for primary breast cancer. Aim of this study was to compare prognostic relevance of HER2 status in MBC tested by two different methods i.e. immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). HER2 status of the same group of 107 MBC patients was determined by IHC (protein overexpression) and by CISH (gene amplification). HER2 results obtained by IHC and CISH showed significant correlation, beside the existence of discrepancies. Beside the significant correlation in two methods, there was a difference in prognostic values of compared methods during the course of metastatic disease. There was a significant difference in progression-free interval (PFI) between HER2 non-amplified and HER2 amplified cases determined by CISH, in postmenopausal subgroup and node-positive subgroup, but no significant difference for IHC stratified MBC patients. CISH seems to be accurate and more informative method than IHC regarding prognostic value of HER2 in metastatic breast cancer. PMID- 17335804 TI - Activated myeloid dendritic cells accumulate and co-localize with CD3+ T cells in coronary artery lesions in patients with Kawasaki disease. AB - Emerging evidence implicating the participation of dendritic cells (DCs) and T cells in various vascular inflammatory diseases such as giant cell arteritis, Takayasu's arteritis, and atherosclerosis led us to hypothesize that they might also participate in the pathogenesis of coronary arteritis in Kawasaki disease (KD). Coronary artery specimens from 4 patients with KD and 6 control patients were obtained. Immunohistochemical and computer-assisted histomorphometric analyses were performed to detect all myeloid DCs (S-100(+), fascin(+)), all plasmacytoid DCs (CD123(+)) as well as specific DC subsets (mature myeloid DCs [CD83(+)], myeloid [BDCA-1(+)] and plasmacytoid DC precursors [BDCA-2(+)]), T cells (CD3(+)), and all antigen-presenting cells (HLA-DR(+)). Co-localization of DCs with T cells was assessed using double immunostaining. Significantly more myeloid DCs at a precursor, immature or mature stage were found in coronary lesions of KD patients than in controls. Myeloid DC precursors were distributed equally in the intima and adventitia. Mature myeloid DCs were particularly abundant in the adventitia. There was a significant correlation between mature DCs and HLA-DR expression. Double immunostaining demonstrated frequent contacts between myeloid DCs and T cells in the outer media and adventitia. Plasmacytoid DC precursors were rarely found in the adventitia. In conclusion, coronary artery lesions of KD patients contain increased numbers of mature myeloid DCs with high HLA-DR expression and frequent T cell contacts detected immunohistochemically. This suggests that mature arterial myeloid DCs might be activating T cells in situ and may be a significant factor in the pathogenesis of coronary arteritis in KD. PMID- 17335805 TI - Laminin-5-deficient human keratinocytes: defective adhesion results in a saltatory and inefficient mode of migration. AB - Laminin-5 is a major adhesion protein of the skin basement membrane and crucially involved in integrin-mediated cell substrate attachment of keratinocytes, which is important for hemidesmosomal anchorage as well as for keratinocyte migration during epidermal wound healing. To investigate its role in keratinocyte migration, we analyzed laminin-5-deficient cells of patients with a lethal variant of junctional epidermolysis bullosa. Normal migrating keratinocytes adopted monopolar morphology with a distinct front lamella and employed a continuous mode of translocation. In contrast, laminin-5-deficient cells assumed a stretched bipolar shape with two lamella regions and migrated in a discontinuous, saltatory manner characterized by significantly decreased directional persistence and reduced migration velocity. The distinct morphology as well as the migratory phenotype apparently resulted from a defect in the formation of cell substrate adhesions that were completely missing in the cell body and less stable in the lamella regions. Accordingly in normal keratinocytes, a bipolar shape and a saltatory migration mode were inducible by blocking laminin 5-mediated substrate adhesion. Our findings clearly point to an essential role of laminin-5 in forming dynamic cell substrate adhesion during migration of epidermal keratinocytes and provide an explanation for the cellular mechanisms that underlie the lethal form of junctional epidermolysis bullosa. PMID- 17335806 TI - Heme carrier protein 1 (HCP1) expression and functional analysis in the retina and retinal pigment epithelium. AB - The retina and retinal pigment epithelium (RPE) are present in the posterior segment of the eye, and the retina is dependent upon the underlying RPE for normal function. The retina is the most oxygenated tissue in the body but is isolated from the blood circulation by blood-retinal barriers. Metabolism of cellular oxygen involves heme but little is known about heme transport in the retina and RPE. Here we report the identification from bovine RPE of a heme transporter bHcp1 (bovine heme carrier protein 1) that is homologous to mouse intestinal HCP1 expressed in duodenal enterocytes. Similar to the mouse protein, bHcp1 exhibited heme uptake ability in Xenopus oocytes and localized to the cell membrane in cultured mammalian epithelium. Whereas bHcp1 expression was detected only in bovine RPE, expression of its human homologue was identified in both retina and RPE. Furthermore, the data revealed low-level wider expression of human HCP1 transcript in multiple tissues suggesting that it is responsible for heme transport in the body, not the intestine alone. Expression of HCP1 in the RPE and retina indicates the mechanism of heme transport in these ocular tissues. PMID- 17335807 TI - Constitutive diffuse activation of phosphoinositide 3-kinase at the plasma membrane by v-Src suppresses the chemotactic response to PDGF by abrogating the polarity of PDGF receptor signalling. AB - Cancer cells depend on chemotaxis for invasion and frequently overexpress and/or activate Src. We previously reported that v-Src accelerates motility by promoting phosphoinositide 3-kinase (PI3-K) signalling but abrogates chemotaxis. We here addressed the mechanism of the loss of chemotactic response to platelet-derived growth factor (PDGF) gradients in fibroblasts harbouring a thermosensitive v-Src kinase. At non-permissive temperature, PDGF receptor (PDGFR) signalling, assessed by phosphoY(751)-specific antibodies (a docking site for PI3-K), was not detected without PDGF and showed a concentration-dependent PDGF response. Both immunolabeling of PI3-K (p110) and live cell imaging of its product (phosphatidylinositol 3,4,5 tris-phosphate) showed PI3-K recruitment and activation at lamellipodia polarized towards a PDGF gradient. Centrosomes and PDGFR- and Src-bearing endosomes were also oriented towards this gradient. Upon v Src thermoactivation, (i) Y(751) phosphorylation was moderately induced without PDGF and synergistically increased with PDGF; (ii) PI3-K was recruited and activated all along the plasma membrane without PDGF and did not polarize in response to a PDGF gradient; and (iii) polarization of centrosomes and of PDGFR bearing endosomes were also abrogated. Thus, PDGF can further increase PDGFR auto phosphorylation despite strong Src kinase activity, but diffuse downstream activation of PI3-K by Src abrogates cell polarization and chemotaxis: "signalling requires silence". PMID- 17335808 TI - Hypoxia-inducible factor 1alpha regulates lung adenocarcinoma cell invasion. AB - We studied the role of hypoxia-inducible factor-1alpha (HIF-1alpha) in human lung adenocarcinoma cell invasion using a metastatic cell model composed of low invasive CL1 and highly invasive CL1-5 cells. We showed that HIF-1alpha was expressed in CL1-5 but not in CL1 cells under normoxic condition, and that inhibition of HIF-1alpha expression by a small interfering RNA decreased invasiveness of CL1-5 cells. Complementary, overexpression of HIF-1alpha increased the invasiveness of CL1 and gastric cancer SC-M1 cells. Subsequently, we showed that urokinase-type plasminogen activator receptor (uPAR), and matrix metalloproteinases (MMPs) 1 and 2 were critical in HIF-1alpha-induced invasion. Mechanistic studies revealed that HIF-1alpha overexpression could increase the expression of uPAR and MMP1, but not MMP2. However, ELISA assays on the conditioned media generated from control CL1 and CL1 cells overexpressing HIF 1alpha showed that overexpression of HIF-1alpha increased the levels of endogenous free active MMP2 and total free MMP2, and the former was blocked by inhibition of MMP1 expression. We conclude that (i) HIF-1alpha overexpression enhances lung cancer cell invasion at least through up-regulating the expression and activities of uPAR, MMP1, and MMP2; and (ii) induction of MMP1 participates in cell invasion and also plays an important role in HIF-1alpha-induced activation of MMP2. PMID- 17335809 TI - Effects of insulin-like growth factor 1 on synaptic excitability in cultured rat hippocampal neurons. AB - Insulin-like growth factor 1 (IGF-1) has important functions in the brain, including metabolic, neurotrophic, neuromodulatory and neuroendocrine actions, and it also prevents beta amyloid-induced death of hippocampal neurons. However, its functions in the synaptic excitability remain uncertain. Here we investigated the effects of IGF-1 on synaptic excitability in cultured rat hippocampal neurons using whole-cell patch clamp recordings. Incubation the hippocampal neurons with different concentrations of IGF-1 for 24 h or 30 min significantly increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), but had no effect on the frequency of miniature EPSCs (mEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs). The mean amplitudes, rise, and decay kinetics of sEPSCs, mEPSCs, and sIPSCs were not significantly affected by IGF-1, indicating that IGF-1 increased the probability of neurotransmitter release but did not modulate postsynaptic receptors. The effects of IGF-1 were mediated by mitogen activated protein kinase (MAPK). IGF-1 activated the ERK1/2 signaling pathway in cultured hippocampal neurons, and the inhibitor PD98059 blocked the enhancement of sEPSCs induced by IGF-1. These results demonstrated the regulatory function of IGF-1 on synaptic excitability in hippocampal neurons and its underlying signaling mechanism. PMID- 17335810 TI - Excessive synchronization of basal ganglia neurons at 20 Hz slows movement in Parkinson's disease. AB - Excessive synchronization of neuronal activity at around 20 Hz is a common finding in the basal ganglia of patients with untreated Parkinson's disease (PD). Correlative evidence suggests, but does not prove, that this spontaneous activity may contribute to slowness of movement in this condition. Here we investigate whether externally imposed synchronization through direct stimulation of the region of the subthalamic nucleus at 20 Hz can slow motor performance in a simple unimanual tapping task and whether this effect is frequency selective. Tapping rates were recorded on 42 sides in 22 patients with PD after overnight withdrawal of medication. Tapping was performed without stimulation and during bilateral stimulation at 20 Hz, 50 Hz and 130 Hz. We found that tapping rates were slowed by 8.2+/-3.2% (p=0.014) during 20-Hz stimulation in subjects with relatively preserved baseline function in the task. This effect was frequency selective. The current data provide proof of the principle that excessive beta synchrony within the basal ganglia-cortical loop may contribute to the slowing of movements in Parkinson's disease. PMID- 17335811 TI - The selective kappa-opioid receptor agonist U50,488 reduces L-dopa-induced dyskinesias but worsens parkinsonism in MPTP-treated primates. AB - Several lines of evidence demonstrate that the striatal enkephalinergic system may be involved in the development of LIDs. Preproenkephalin-B (PPE-B) transcript levels are elevated with LIDs and there are also declines in kappa-opioid and other opioid receptors in different regions of the basal ganglia. If reduced kappa-opioid receptors are linked to LIDs, it is possible that drugs that stimulate this subtype may decrease dyskinesias. We therefore initiated experiments to investigate the effect of kappa-opioid receptor activation on LIDs. We first tested the selective kappa-agonist U50,488 in rats with unilateral lesions of the nigrostriatal pathway. Chronic L-dopa treatment induced abnormal involuntary movements, including axial, orolingual and forelimb dyskinesias contralateral to the lesion. U50,488 administration prior to L-dopa treatment reduced these movements by 70%, suggesting that U50,488 has potential as an anti dyskinetic treatment. We next tested its effect in a parkinsonian nonhuman primate model, which offers the advantage that parkinsonism and LIDs can clearly be differentiated and that the dyskinesias are similar to those in parkinsonian patients. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys were treated with L-dopa (5 mg/kg p.o.) twice daily for 3 weeks to induce dyskinesias. As in the rodent model, U50,488 (0.1-1.0 mg/kg i.m.) decreased LIDs in a dose-dependent fashion. However, the anti-parkinsonian effect of L-dopa was similarly reduced, and side effects developed, including sedation and vomiting. These data suggest that kappa-opioid agonists such as U50,488 may not be clinically useful antidyskinetic agents because they also reverse the anti parkinsonian effect of l-dopa. PMID- 17335812 TI - NGF mRNA is expressed in the dorsal root ganglia after spinal cord injury in the rat. AB - Nerve growth factor (NGF) mRNA is expressed in a variety of cell types in the injured spinal cord and its protein implicated in both positive and negative neurological outcomes of cord injury. Here we demonstrate that NGF mRNA is also upregulated in dorsal root ganglion (DRG) neurons after spinal cord injury and that the percentage of sensory neurons expressing NGF mRNA correlates with proximity to the lesion epicenter. Our data suggest that, in DRG, NGF gene expression may be upregulated by damage to the central processes of sensory neurons. PMID- 17335813 TI - Pharmacological evaluation of anti-leishmanial activity by in vivo nitric oxide modulation in Balb/c mice infected with Leishmania major MRHO/IR/75/ER: an Iranian strain of cutaneous leishmaniasis. AB - Cutaneous leishmaniasis with a variation in its clinical signs is still one of the health problems in the world, region and Iran. Immune responses against leishmania consist of cytokines, immune cells and mediators. Macrophages participate actively in the inflammatory response by releasing chemokines and mediators including nitric oxide (NO) and reactive oxygen and nitrogen intermediates. This study investigates whether NO had anti-leishmanial effects and/or mediated pathology in mice infected with Leishmania major MRHO/IR/75/ER (IR/75). NO inducer lipopolysaccharide (LPS) and NO donor S-nitrosoglutathione (SNOG) were used for their ability to increase RNI and to modify leishmania infection in susceptible Balb/c mice, in order to evaluate the effects of NO production on size and lesion macroscopy, delay of lesion formation and proliferation of amastigotes inside macrophages. Liver, spleen and lymph nodes were also studied as target organs to detect amastigotes. In addition to plasma, liver and spleen suspensions were investigated for NO induction by using Griess microassay. Statistical analysis of data revealed an association between increases in NO level with the pathology of disease in Balb/c mice infected with L. major IR/75. The survival of leishmania parasite inside the macrophages and its proliferation was affected by LPS and SNOG-treatments. An inconsistent relationship was evident between the NO modulation and pathological changes in treated Balb/c mice infected with L. major IR/75. PMID- 17335814 TI - Toxoplasma gondii: inconsistent dissemination patterns following oral infection in mice. AB - Since Toxoplasma gondii is transmitted in the wild through the ingestion of infective cysts, oral infection is a preferred model for studying the natural mode of parasite dissemination and pathogenesis. Using luciferase-expressing strains of T. gondii and in vivo imaging, we observed different patterns of disease progression in mice depending of the method of oral infection. Oral gavage of infective cysts (e.g., bradyzoites) resulted in an inconsistent pattern of parasite dissemination; in the majority (20/29) of infected mice, luciferase derived signal (indicating high numbers of Toxoplasma tachyzoites) was first observed in the right chest area. At later time points this signal spread to other parts of the mouse, including the abdominal area. In the remaining mice (9/29), parasites were first observed replicating in the abdominal area, as might be expected. In contrast, when mice were infected naturally (either via ingestion of whole brains from previously infected mice or brain cyst homogenate-soaked bread), parasites were first observed replicating in the abdominal area in all mice examined (10/10). Based on the inconsistency of infections initiated with oral gavage, it is recommended that natural feeding be used to infect mice when a consistent oral infection is desired. PMID- 17335815 TI - Expression of the CUB domain containing protein 1 (CDCP1) gene in colorectal tumour cells. AB - Expression of CUB domain containing protein 1 (CDCP1) is upregulated in carcinoma cells. We quantitated CDCP1 gene expression in matched normal colon and tumour tissue and compared the level of expression to other genes upregulated in colorectal tumourigenesis. Furthermore, we show that the CDCP1 gene generates two transcripts which are co-expressed in normal and matched tumour tissue as well as in the majority of cell lines analysed. However, intracellular localisation studies revealed that only one of these transcripts encodes a protein that is localised to the cell surface. PMID- 17335816 TI - Regulating cytoskeleton-based vesicle motility. AB - During vesicular transport, the assembly of the coat complexes and the selection of cargo proteins must be coordinated with the subsequent translocation of vesicles from the donor to an acceptor compartment. Here, we review recent progress toward uncovering the molecular mechanisms that connect transport vesicles to the protein machinery responsible for cytoskeleton-mediated motility. An emerging theme is that vesicle cargo proteins, either directly or through binding interactions with coat proteins, are able to influence cytoskeletal dynamics and motor protein function. Hence, a vesicle's cargo composition may help direct its intracellular motility and targeting. PMID- 17335817 TI - A polymorphism of the interleukin-1 beta gene is associated with sperm pathology in humans. AB - In a prospective case-control study of 127 normozoospermic and 435 non normozoospermic Caucasian men, the genotype frequencies of a polymorphism of the interleukin-1 beta gene (IL-1beta Taq C-->T) were statistically significantly different between groups (homozygous wild-type C/C [57%], heterozygous C/T [42%], and homozygous mutant T/T [1%] vs. C/C [57%], C/T [36%], T/T [7%] for normozoospermic and non-normozoospermic men, respectively; odds ratio, 4.8; 95% confidence interval, 1.13 to 20.28). This association was restricted to men with the oligoasthenoteratozoospermia (OAT) syndrome. We conclude that the investigated polymorphism is associated with sperm pathology in Caucasians. PMID- 17335818 TI - N-acetyl cysteine vs. metformin in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective randomized controlled study. AB - OBJECTIVE: To compare the effect of N-acetyl cysteine and metformin on hormonal profile (insulin and T) and ovulation rate in women with clomiphene citrate resistant polycystic ovary syndrome. DESIGN: Prospective randomized controlled study. SETTING: Department of obstetrics and gynecology in a university hospital in Egypt. PATIENT(S): Sixty-one infertile women with clomiphene citrate-resistant polycystic ovary syndrome were assigned randomly to receive either metformin (1,500 mg/d) or N-acetyl cysteine (1.8 g/d) for 6 weeks. INTERVENTION(S): Hormonal profile was determined before and after the course of treatment. Folliculometry was performed to assess ovulation. MAIN OUTCOME MEASURE(S): Ovulation rate and insulin and T changes. RESULT(S): In the metformin group, there was a significant decrease in the fasting glucose, fasting insulin, and total T. In the N-acetyl cysteine group, there was no significant difference in the fasting glucose or fasting insulin and there was a significant decrease in total T. There was no significant difference in the fasting glucose-fasting insulin ratio in both groups. In the metformin group, the rate of ovulation was 51.6% (16/31), vs. 6.7% (2/30) in the N-acetyl cysteine group, which was statistically significant. CONCLUSION(S): Metformin alone is an effective drug in inducing ovulation in clomiphene citrate-resistant polycystic ovary syndrome, whereas N-acetyl cysteine alone is not. Further large studies are required to confirm our results. PMID- 17335819 TI - Improvements achieved in an oocyte donation program over a 10-year period: sequential increase in implantation and pregnancy rates and decrease in high order multiple pregnancies. AB - OBJECTIVE: To compare outcome parameters and cumulative pregnancy rates (PRs) in oocyte donation cycles over a period of 10 years. DESIGN: Retrospective study. SETTING: University-affiliated assisted reproductive technology program. PATIENT(S): Women undergoing oocyte donation (10,537 cycles) between 1995 and 2005. INTERVENTION(S): Ovarian stimulation and oocyte retrieval in donors. Embryo transfer performed in recipients after endometrial preparation. MAIN OUTCOME MEASURE(S): Outcome parameters and cumulative PRs were calculated and compared in relation to indication, age, and origin of sperm used. RESULT(S): Overall PR, implantation rate, clinical PR, and miscarriage rate per embryo transfer performed were 54.9%, 27%, 50.3%, and 19%, respectively. Ongoing PR per transfer was 40.2%, and twin and high-order multiple PRs were 39% and 6%, respectively. Mean number of embryos transferred was reduced from 3.6 +/- 0.8 to 1.9 +/- 0.3, implantation rate improved from 16.7% to 38.3%, and ongoing PR improved from 31% to 44.3%. Cumulative PRs did not differ significantly among different indications for oocyte donation, age groups, or origin of sperm used for oocyte insemination. Overall cumulative PRs after three and five cycles were calculated as 87% and 96.8%, respectively. CONCLUSION(S): Significant improvements in outcome parameters were achieved within 10 years. Similar cumulative PRs were observed regardless of recipient age, indication for oocyte donation, or sperm origin. PMID- 17335820 TI - Increased plasma visfatin concentrations in women with polycystic ovary syndrome. AB - OBJECTIVE: To test the hypothesis that plasma visfatin concentrations will be higher in women with polycystic ovary syndrome (PCOS) than in women without PCOS. DESIGN: Clinical study. SETTING: University hospital. PATIENT(S): A total of 52 women were evaluated. Twenty-six had PCOS, and the remaining 26 were healthy women with regular menstrual cycles who served as control subjects. INTERVENTION(S): Plasma visfatin concentrations were analyzed with the use of RIA. MAIN OUTCOME MEASURE(S): Serum concentrations of FSH, LH, TSH, PRL, T, insulin, E(2), and visfatin. RESULT(S): Plasma visfatin concentrations were significantly higher in the PCOS group (336.8 +/- 50.2 ng/mL) than in the healthy control group (282.4 +/- 43.3 ng/mL). Logistic regression analysis indicated a significant association between odds ratio (OR) values of PCOS and visfatin levels (OR = 2.81; 95% confidence interval [CI], 2.74-2.90), T (OR = 3.39; 95% CI, 2.85-4.16), and LH levels (OR = 3.49; 95% CI, 2.79-4.56). There was no correlation between plasma visfatin concentrations and T, insulin, and LH levels or age in either the PCOS group or the control group. We observed that plasma visfatin levels were positively correlated with body mass index in the PCOS group (r = 0.396, r(2) = 0.157) but not in the control group (r = -0.328, r(2) = 0.108). CONCLUSION(S): Our data show that women with PCOS exhibit higher plasma visfatin levels than control subjects of similar body mass index. Further studies are required to clarify the etiology and effects of hypervisfatinemia in women with PCOS. PMID- 17335821 TI - Effect of implanted Cu/low-density polyethylene nanocomposite on the morphology of endometrium in the mouse. AB - OBJECTIVE: To investigate the damage of endometrium caused by the implanted Cu/low-density polyethylene (LDPE) nanocomposite and the contraceptive effect of this novel copper-containing intrauterine device material. DESIGN: Experimental animal study. SETTING: TongJi Medical College of Huazhong University of Science and Technology. PATIENT(S): Sixty healthy female mice. INTERVENTION(S): Twenty mice received no implants, 20 mice received the Cu/LDPE nanocomposite, and 20 mice received bulk copper. MAIN OUTCOME MEASURE(S): Morphologic features of the endometrium, contraceptive effect, and surface condition of the implanted implants. RESULT(S): The contraceptive effect of both the Cu/LDPE nanocomposite and bulk copper is 100%, the damage of the endometrium caused by the Cu/LDPE nanocomposite is much less than that caused by bulk copper, and the surface of the implanted Cu/LDPE nanocomposite is much smoother and much softer than that of the implanted bulk copper. CONCLUSION(S): The contraceptive effect of the Cu/LDPE nanocomposite is comparable with that of bulk copper, and the damage of the endometrium caused by the Cu/LDPE nanocomposite is much less than that caused by bulk copper. The endometrium injury is related to the surface condition of the implanted intrauterine device material. PMID- 17335822 TI - Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro. AB - OBJECTIVE: To determine whether sildenafil citrate, a cyclic monophosphate specific type 5 phosphodiesterase inhibitor, influences sperm motility or the acrosome reaction. DESIGN: Laboratory analysis of sperm motility after exposure to sildenafil citrate using computer-assisted semen analysis and acrosome reaction by fluorescein isothiocyanate-labeled peanut agglutinin staining. SETTING: An assisted reproductive technology (ART) unit. PATIENT(S): Fifty-seven male patients. INTERVENTION(S): Sperm were divided into 90% (those with the best fertilizing potential used in assisted conception) and 45% (the poorer population) fractions by density centrifugation and incubated with sildenafil citrate (0.67 muM) at 37 degrees C for up to 180 minutes. MAIN OUTCOME MEASURE(S): Both the number and velocity of progressively motile sperm were significantly increased by sildenafil citrate between 15 and 135 minutes. Furthermore, samples revealed that these effects were consistent in the 90% and 45% populations of sperm. In both populations, sildenafil also caused a significant increase in the proportion of acrosome-reacted sperm-22.1% compared with 11.8% in the control group of the good quality fraction and 16.6% compared with 9.4% in the control group of the poorer quality fraction. CONCLUSION(S): The use of sildenafil citrate may adversely affect male fertility. PMID- 17335824 TI - Changes in olfactory function in pregnancy and postpartum. AB - OBJECTIVE: To track changes in olfactory performance during pregnancy and the postpartum. METHODS: In a prospective study the olfactory function of 38 pregnant women was assessed at about 12, 21, and 36 weeks of pregnancy and 7 weeks after delivery. A control group of 46 nonpregnant women were also asked to rate the intensity and hedonic tone of 10 "natural" odors. RESULTS: There was no difference in olfactory performance between the women in the first trimester of pregnancy and the controls, but at approximately 36 weeks of pregnancy the pregnant women experienced a decreased odor threshold compared with the nonpregnant controls, and this decrease was still present after delivery. There was no significant difference between the groups in capacity for odor discrimination or odor identification. "Objective" decreases were observed even though pregnant women rated their olfactory sensitivity significantly higher than the controls. Although the 2 groups did not differ with regard to intensity ratings of the 10 "natural" odors, there were differences with regard to the hedonic ratings. CONCLUSION: Pregnancy is accompanied by changes in olfactory performance. Changes in hedonic odor ratings indicate a potential embryo protective mechanism. The discrepancy between "objective" and "subjective" olfactory function may relate to changes in the cognitive processing of chemosensory information during pregnancy. PMID- 17335823 TI - Cognitive performance in rhesus monkeys varies by sex and prenatal androgen exposure. AB - Men and women differ on performance and strategy on several spatial tasks. Rodents display similar sex differences, and manipulations of early hormone exposure alter the direction of these differences. However, most cognitive testing of nonhuman primates has utilized sample sizes too small to investigate sexually differentiated behaviors. This study presents an investigation of sex differences and the effects of prenatal androgen on spatial memory and strategy use in rhesus monkeys. Monkeys prenatally exposed to vehicle, testosterone, or the androgen receptor blocker flutamide performed a search task in which 5 of 12 goal boxes contained food rewards. Spatial consistency and the presence of local landmarks were varied. Performance when both spatial and marker cues were available did not differ by sex or prenatal treatment. Contrary to predictions, females easily solved the task when local markers were removed, and their performance outscored males. Although eliminating spatial consistency and requiring subjects to use local markers impaired performance by all monkeys, females continued to locate correct goal boxes at higher than chance levels and scored better than males. Blocking prenatal androgen exposure in males improved use of local markers. These findings suggest that the tendency to attend to landmarks and to use them in solving spatial problems is typical of females across many species, including rodents, humans, and rhesus monkeys. In rhesus monkeys and rodents, developmental androgen eliminates this specialization. However, these results are the only known example of better performance of females than males when salient markers are removed. PMID- 17335825 TI - Expression of cartilage-specific markers in calcified and non-calcified atherosclerotic lesions. AB - Recently, molecular mechanisms resembling endochondral ossification were suggested to be important for atherosclerotic vessel calcification. The aim of this study was to investigate in a series of human atherosclerotic (non-diabetic) lesions of the crural arteries the distribution and expression of classical marker genes of the endochondral ossification pathway. Immunostaining for marker proteins S-100 protein and collagen types II and X were performed on atherosclerotic lesions of different grades (according to Stary). Quantitative real-time PCR for human COL1A1, COL2A1, COL10A1, SOX9, and BMP-2 was applied on RNA isolated from atherosclerotic arteries. In most samples, no expression of collagen type II and S-100 protein was found. Exceptionally, S-100 protein and type II collagen expression was observed very focally within advanced atherosclerotic plaques. Type X collagen was not detected in any of the lesions investigated. Overall, in our study we found no evidence that chondrogenic differentiation pathways are generally active in atherosclerotic plaque formation. In particular type X collagen, one important molecule in cartilage calcification, was not expressed in any of the investigated specimens. Occasionally, however, chondrocytic differentiation markers occur within atherosclerotic lesions. This most likely represents a metaplastic event associated, but not causative for atherosclerotic vessel degeneration and calcification. PMID- 17335826 TI - Hepatic steatosis is associated with a greater prevalence of coronary artery calcification in asymptomatic men. PMID- 17335827 TI - Statin treated patients have reduced intraplaque angiogenesis in carotid endarterectomy specimens. AB - BACKGROUND: Treatment with statins is considered a first line therapy in atherosclerotic disease. Intraplaque angiogenesis is involved in plaque progression and instability. It remains unclear whether the beneficial effect of statin treatment in humans is achieved through reduced intraplaque angiogenesis. The aim of this study was to evaluate the capillaries density in carotid plaques removed from patients treated with statin versus untreated patients. METHODS AND RESULTS: We studied 102 patients who underwent carotid endarterectomy: 98 of them met the inclusion criteria and entered the study; 75 men and 23 women; mean age 66+/-8 years (range 42-83 years). Forty-three patients (44%) were on statin treatment at least 3 months before endarterectomy and 55 (56%) had never received statin treatment. The intensity of intraplaque angiogenesis was evaluated with immunohistochemistry using the antibody CD34. The number of capillaries per mm(2) was measured with a custom designed image tool analysis. With the exception of serum total cholesterol levels and serum low-density cholesterol levels, the two groups of patients did not vary significantly in cardiovascular risk factors and in parameters pertaining to the procedure profile. Patients on statin treatment had less capillaries per mm(2) than patients not receiving this kind of drugs (0.97+/-0.61 per mm(2) versus 1.39+/-0.98 per mm(2), p=0.031). Univariate associations between possible explanatory variables and number of capillaries per mm(2) were tested using Spearman rank R. Variables associated with a p-value <0.20 (age, serum creatinine, serum total cholesterol, serum low-density lipoprotein, serum homocysteine, presence of diabetes mellitus and statin treatment) were entered in a multivariable model. Multivariate analysis showed that statin treatment was the only independent predictor (t=-5.39, p<0.001) of intraplaque angiogenesis. CONCLUSIONS: Statin therapy is associated with reduced intraplaque angiogenesis in the carotid arteries. This could provide an explanation for the beneficial effects of this kind of drug on patients with atherosclerotic disease. PMID- 17335828 TI - Body weight, plasma insulin, and coronary events with gemfibrozil in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). AB - BACKGROUND: The Veterans Affairs High-Density Lipoprotein Intervention Trial (VA HIT) showed that gemfibrozil significantly reduced major coronary events in men with known coronary heart disease (CHD). To better understand why therapy was especially effective with obesity, diabetes, and hyperinsulinemia, changes in body weight and plasma insulin were determined after 1 year of gemfibrozil or placebo therapy and related to changes in lipids and CHD events. RESULTS: With gemfibrozil significantly more subjects lost weight (51.7% versus 38.6%, P<0.0001) and significantly fewer subjects gained weight (42.5% versus 54.0%, P<0.0001) than with placebo. Both a greater loss and smaller gain in weight with gemfibrozil were age-related and significant in subjects > or =66 years (median age), but not in younger subjects. Weight change was paralleled by changes in insulin. With gemfibrozil, CHD events were significantly reduced with weight loss (hazard ratio [HR], 0.61; 95% CI, 0.44-0.84; P=0.002) and, particularly, with diabetes or hyperinsulinemia (HR, 0.53; 95% CI, 0.34-0.83; P=0.006). In contrast, CHD events were not significantly reduced without weight loss (HR, 0.83; 95% CI, 0.62-1.12; P=0.22). CONCLUSIONS: In VA-HIT, gemfibrozil resulted in weight loss associated with reductions in insulin. With weight loss gemfibrozil produced a significant reduction in CHD events that did not occur in the absence of weight loss. PMID- 17335829 TI - A rare polymorphism in the low density lipoprotein (LDL) gene that affects mRNA splicing. AB - Familial hypercholesterolaemia (FH) is usually caused by mutations in the low density lipoprotein (LDL) receptor gene (LDLR) that impair clearance of LDL from the circulation. The increased risk of premature coronary heart disease associated with FH can be reduced by dietary advice and treatment with lipid lowering drug therapy, but it is important to identify affected individuals at an early stage. Several programmes for genetic diagnosis of FH that rely on identifying nucleotide substitutions in genomic DNA have been initiated, but the validity of these is dependent on distinguishing between a silent nucleotide variant and a mutation that affects LDL-receptor function. Here we describe a single nucleotide substitution in the coding region of exon 9 of LDLR that is an apparently silent polymorphism: CGG (Arg406) to AGG (Arg). Analysis of mRNA from the patient's cells showed that the mutation introduces a new splice site that is used to the exclusion of the natural splice site and causes a deletion of 31 bp from the mRNA, predicted to introduce premature termination four codons after R406. This finding emphasizes the caution needed in genetic diagnosis of FH based on genomic DNA sequence alone. PMID- 17335830 TI - Endothelium-dependent vasodilation, insulin resistance and the metabolic syndrome in an elderly cohort: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. AB - BACKGROUND: Only a few previous studies have investigated endothelium-dependent vasodilation in the metabolic syndrome (MetS). In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, different techniques to assess vasodilation in conduit and resistance arteries were evaluated in relation to the MetS and insulin resistance. METHODS: In this population-based study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. RESULTS: EDV was lower in subjects with the MetS (NECP/ATP III-criteria, prevalence 23%) compared to those without (p<0.0001), and declined with increasing number of MetS criteria (p<0.0001), after adjustment for coronary heart disease, stroke and cardiovascular medication. Also a reduced pulse wave response (p=0.015), but not FMD (p=0.64), was seen in those with the MetS. EDV and the pulse wave response, but not FMD, were inversely related to insulin resistance evaluated by the HOMA index. Also endothelium-independent vasodilation (EIDV) induced by intra-brachial infusion of sodium nitroprusside was impaired in subjects with MetS and in insulin resistance. CONCLUSIONS: Vasodilation evaluated with the invasive forearm technique and pulse wave analysis with a beta-2 agonist, but not FMD, was reduced in elderly subjects with the MetS and was related to insulin resistance. Also EIDV showed the same pattern, suggesting a general deterioration in vasoreactivity mainly in resistance arteries in elderly subjects with the MetS. PMID- 17335831 TI - Patients with a history of stable or unstable coronary heart disease have different acute phase responses to an inflammatory stimulus. AB - Increased levels of acute phase proteins (APP) in serum are associated with vulnerability of atherosclerotic plaques and acute manifestations of coronary heart disease (CHD). APP have been viewed as indexes of active vascular inflammation or as mediators of atherothrombosis. In the present study we tested the hypothesis that individuals who develop stable or unstable forms of CHD might have different innate responses to an inflammatory stimulus. We compared changes in plasma C-reactive protein (CRP) and serum amyloid A (SAA) concentrations 48 h after a standardized inflammatory stimulus (adjuvanted influenza vaccination) in patients with quiescent CHD that had been manifested at onset as inducible myocardial ischemia (Group 1, n=26) or as acute coronary syndromes (ACS) (Group 2, n=34). Selected patients were free from inflammatory or other conditions that might affect the immune response. CRP concentration increased significantly after vaccination in both groups (Group 1: 0.47 [0.21-0.86] to 0.56 [0.32-1.17]mg/L, p=0.005; Group 2: 0.64 [0.21-1.09] to 0.75 [0.33-1.48]mg/L, p=0.003), without significant differences between groups in absolute or percentage changes. By contrast, SAA did not change after vaccination in Group 1 (14.4 [8.9-19.5] to 14.8 [10.3-18.8]mg/L, p=0.88) but increased significantly in Group 2 (16.9 [10.0 21.5] to 19.2 [11.3-29.1]mg/L, p=0.002), with significant differences between the groups in absolute and percentage terms (p=0.015 and 0.019, respectively). Changes in CRP and SAA, both absolute and percentage, were significantly correlated in Group 2 (r=0.60 and 0.66, both p<0.001). The responsiveness of plasma SAA to an inflammatory stimulus in Group 2 alone suggests a pro inflammatory status in patients prone to acute coronary syndrome but not in those with inducible myocardial ischemia. PMID- 17335832 TI - A new imaging technique to study 3-D plaque and shear stress distribution in human coronary artery bifurcations in vivo. AB - OBJECTIVE: Bifurcations of coronary arteries are predilection sites for atherosclerosis and expansive remodeling, the latter being associated with plaque vulnerability. Both are related to blood flow-induced shear stress (SS). We present a new approach to generate 3-D reconstructions of coronary artery bifurcations in vivo and investigate the relationship between SS, wall thickness (WT) and remodeling. METHODS: The patient specific 3-D reconstruction of the main branch of the bifurcation was obtained by combining intravascular ultrasound and biplane angiography, and the 3-D lumen of the side branch was based on biplane angiography only. The two data sets were fused and computational methods were applied to determine the SS distribution, using patient derived flow and viscosity data. The intravascular ultrasound data allowed us to measure local WT and remodeling in the main branch. RESULTS: The lumen reconstruction procedure was successful and it was shown that the impact of the side branch on SS distribution in the main branch diminished within 3mm. Distal to the bifurcation, two continuous regions in the main branch were identified. In the proximal region, we observed lumen preservation, and expansive remodeling. Although a plaque was observed in the low SS region at the non-divider wall, no relationship between SS and WT was found. In the distal region, we observed lumen narrowing and a significant positive relationship between SS and WT. CONCLUSIONS: A new imaging technique was applied to generate a 3-D reconstruction of a human coronary artery bifurcation in vivo. The observed relationship between SS, WT and remodeling in this specific patient illustrates the spatial heterogeneity of the atherosclerosis in the vicinity of arterial bifurcations. PMID- 17335833 TI - Simplifying capillary electrophoresis-mass spectrometry operation: eliminating capillary derivatization by using self-coating background electrolytes. AB - To simplify capillary electrophoresis-mass spectrometry (CE-MS) operation, a background electrolyte (BGE) containing a polymer additive is introduced that allows the analysis of peptides and protein mixtures in underivatized fused silica capillaries without any pretreatment, thereby increasing throughput. The most important characteristic of these polymer additives is that they do not significantly suppress the signals of the proteins and peptides under electrospray ionization, thereby allowing them to be used as an additive to common BGEs that are used for CE-MS analysis of peptide and protein mixtures. In addition, because the fused-silica capillary inner wall is continuously coated with the polymer additive, migration irreproducibility, due to the degradation of the capillary inner wall coating, under CE-MS is minimized. High sensitivity of detection, migration reproducibility, and ease of fabrication allow CE-MS analyses that require long analysis time, such as (CE-MS/MS)n, to be performed with ease. The utility of this background electrolyte has been demonstrated for the analysis of complex protein digests and intact proteins. PMID- 17335834 TI - Comparison of different capillary isoelectric focusing methods--use of "narrow pH cuts" of carrier ampholytes as original tools to improve resolution. AB - Two capillary isoelectric focusing (CIEF) systems have first been optimized: one uses a bare silica capillary and 30% (v/v) of glycerol in the separation medium while the other uses a coated capillary and an aqueous background electrolyte. To perform permanent capillary coating, two neutral polymers have been compared: hydroxypropylcellulose (HPC) and polyvinylalcohol (PVA). HPC coating gave best results for electroosmotic flow (EOF) limitation on a wide pH range: as compared to a bare silica capillary, it allowed to decrease EOF by 96% at pH 7.2 after acidic and basic treatments, whereas PVA coating lead only to a 76% decrease. The glycerol CIEF system was more satisfying for the separation of model proteins classically used as pI markers. Finally, the use of "narrow pH cuts" of carrier ampholytes added to commercial ampholyte mixtures allowed increasing resolution up to a factor 2.4 at a chosen pH for the separation of pI markers and milk proteins. PMID- 17335835 TI - Start-to-end processing of two-dimensional gel electrophoretic images. AB - Gel electrophoresis serves as a basic analytical tool in the proteomic studies. However, processing of gel electrophoretic images is still the main bottleneck of data analysis, and there is an increasing need for the fully automated approaches. The proposed start-to-end strategy of analyzing the gel images consists of chemometric tools, which allow their effective preprocessing, automatic warping, and data modeling. The image preprocessing techniques: denoising in the wavelet domain and the penalized asymmetric least squares approach for the background estimation are proposed. Matching of images is based on fuzzy warping of features, extracted from the gel images. For the classification or calibration purpose, multivariate approaches such, as partial least squares (PLS) or kernel-PLS methods are used. Performance of the proposed strategy is demonstrated on the real set of the two-dimensional gel images. PMID- 17335836 TI - Development of a high-performance liquid chromatography method for the simultaneous quantification of quinoxaline-2-carboxylic acid and methyl-3 quinoxaline-2-carboxylic acid in animal tissues. AB - A method of high-performance liquid chromatography with UV detection has been established for simultaneous quantitative determination of quinoxaline-2 carboxylic acid (QCA) and methyl-3-quinoxaline-2-carboxylic acid (MQCA), the marker residues for carbadox (CBX) and olaquindox (OLA), respectively, in the muscles and livers of porcine and chicken and in the muscle of fish. Tissue samples were subject to acid hydrolysis followed by liquid-liquid extraction and Oasis MAX solid-phase extraction clean-up. The method was validated according to the EU Commission Decision 2002/657/EC. The decision limits (CCalpha) were 0.7 2.6microg/kg and the detection capabilities (CCbeta) were 1.3-5.6microg/kg for QCA and MQCA in tissues. The recoveries of QCA and MQCA, spiked at levels of 2 100microg/kg, were from 70 to 110%; the relative standard deviation values were <20%. This simple, fast and economic method could be applied to the monitoring for the possible misuse of CBX and OLA in animal edible tissue samples. PMID- 17335837 TI - Gly311 residue triggers the enantioselectivity of Staphylococcus xylosus lipase: a monolayer study. AB - Using emulsified triacylglycerols, we have shown recently [Mosbah et al., 2007, submitted for publication] that amino acid residue G311 of Staphylococcus xylosus lipase (SXL) is critically involved in substrate selectivity, pH and temperature dependency. Using the monomolecular film technique, we show in the present study that the four single mutants of this residue (G311L, G311W, G311D, and G311K), interact efficiently with egg-phosphatidyl choline (egg-PC) monomolecular films, comparably to the wild-type (G311). A critical surface pressure (pi(c)) of about 25 mN/m was obtained with the SXL wild-type (SXL-WT) and its mutants. These results support our conclusion that the G311 residue is not involved in the interfacial adsorption step of SXL. A kinetic study on the surface pressure dependency, stereoselectivity, and regioselectivity of SXL-WT and its G311 mutants was also performed using optically pure enantiomers of diacylglycerols (1,2-sn-dicaprin and 2,3-sn-dicaprin) and a prochiral isomer (1,3-sn-dicaprin) spread as monomolecular films at the air-water interface. Our results indicated that the mutation of one single residue at position 311 affects critically the catalytic activity, the stereo- and the regioselectivity of SXL. As previously observed with emulsified substrates [Mosbah et al., 2007, submitted for publication] we observed that an increase in the size of the 311 amino acid side chain residue was accompanied by a decrease of lipase activity measured on dicaprin monolayer. We also noticed that the substitution of G311 by a basic or acidic residue (G311K and G311D), induces a significant shift of the pH optimum from 8 to 9.5 or from 8 to 6.5, respectively. PMID- 17335838 TI - New ceramic-carbon composites for electrodes for electrochemical capacitors. AB - A new class of composite materials is introduced. Fine powders of silica, titania, Y-modified zirconia, and three types of alumina were pressed and sintered to form porous monoliths with relatively uniform pore structure. Carbon was then deposited in the pores of such monoliths by thermal decomposition of dichloromethane, cyclohexene, and glucose. The structure of the carbon deposit was studied by low-temperature nitrogen adsorption and by thermal analysis. The composite materials were used as electrodes in electrochemical capacitors with 1 ethyl-3-methylimidazolium trifluoromethylsulfonate (a low-temperature ionic liquid) as the electrolyte. High capacitances were observed for glucose-derived materials, which had high specific surface areas. PMID- 17335839 TI - Attachment of nanoparticles to the AFM tips for direct measurements of interaction between a single nanoparticle and surfaces. AB - Here we report a universal method of attachment/functionalization of tips for atomic force microscope (AFM) with nanoparticles. The particles of interest are glued to the AFM tip with epoxy. While the gluing of micron size particles with epoxy has been known, attachment of nanoparticles was a problem. The suggested method can be used for attachment of virtually any solid nanoparticles. Approximately every other tip prepared with this method has a single nanoparticle terminated apex. We demonstrate the force measurements between a single approximately 50 nm ceria nanoparticle and flat silica surface in aqueous media of different acidity (pH 4-9). Comparing forces measured with larger ceria particles ( approximately 500 nm), we show that the interaction with nanoparticles is qualitatively different from the interaction with larger particles. PMID- 17335840 TI - Fluorescent organosilica micro- and nanoparticles with controllable size. AB - This paper reports on the synthesis of uniformly dye-doped organosilica particles with narrow size distribution. The particle size can be controlled from tenths of nanometers up to several micrometers, whilst still maintaining monodispersity. Microparticles were observed to swell in various solvents up to approximately 2.5 times their original volume, suggesting the presence of a gel-like internal structure. As shown by confocal microscopy, this morphological control of particle swelling has important implications for the encoding of the nano/micro particles with organic dyes, such as rhodamine B isothiocyanate. Swelling allows the dye to penetrate the organosilica matrix and produce uniformly dye-doped nano and microparticles. Finally, we suggest a coagulation model for the particle formation which significantly differs from conventional Stober synthesis. PMID- 17335841 TI - Responsive colloidal systems: reversible aggregation and fabrication of superhydrophobic surfaces. AB - We report on a method of fabricating stimuli-responsive core-shell nanoparticles using block copolymers covalently bound to a silica nanoparticle surface. We used the "grafting to" approach to graft amphiphilic block copolymer brushes of poly(styrene-b-2-vinylpyridine-b-ethylene oxide) and poly(styrene-b-4 vinylpyridine) onto silica nanoparticles with two different diameters: colloidal silica 200 nm in diameter and fumed silica 15 nm in diameter. We used the pH responsive properties of the grafted brush to regulate the interactions between the particles, and between the particles and their environment. We show that this behavior can be applied for a reversible formation of particle aggregates, and can be used to tune and stabilize the secondary aggregates of particles of the appropriate size and morphology in an aqueous environment. The suspensions of the particles form a textured hydrophilic coating on various substrates upon casting and the evaporation of water. Heating above the polymer's glass transition temperature or treatment in acidic water result in back and forth switching between superhydrophobic and hydrophilic surfaces, respectively. PMID- 17335842 TI - Electrokinetic investigation of surfactant adsorption. AB - Fuerstenau [D.W. Fuerstenau, in: M.L. Hair (Ed.), Dekker, New York, 1971, p. 143] has already discussed the role of hydrocarbon chain of surfactants, the effect of alkyl chain length, chain structure and the pH of the solution on the adsorption process of surfactants. Later Kosmulski [M. Kosmulski, Chemical Properties of Material Surfaces, Surfactant Science Series, vol. 102, Dekker, New York, Basel, 2001] included the effect of surfactant concentration, equilibration time, temperature and electrolyte in his approaches. Certainly, the character of the head groups of the surfactant and the properties of the adsorbent surface are the basis for the adsorption process. Different surfactants and adsorbents cause different adsorption mechanisms described firstly by Rosen [M.J. Rosen, Surfactants and Interfacial Phenomena, second ed., Wiley, New York, 1989]. These adsorption mechanisms and their influencing factors were studied by electrokinetic investigations. Here only changes of the charges at the surfaces could be detected. To control the results of electrokinetic investigations they were compared with results from ellipsometric measurements. In the case of surfactant adsorption the chain length was vitally important. It could be shown by the adsorption of alkyl trimethyl ammonium bromides onto polymer films spin coated at wafer surfaces. The influence of the chain length depending on surface properties of the polymer film was studied. Streaming potential measurements were applied for these investigations. The obtained results enabled us to calculate the molar cohesive free energy per mol of CH2-group in the alkaline chain of the surfactant if all other specific adsorption effects were neglected. PMID- 17335843 TI - Using the Dugdale approximation to match a specific interaction in the adhesive contact of elastic objects. AB - In the Maugis-Dugdale model of the adhesive contact of elastic spheres, the step cohesive stress sigma(0) is arbitrarily chosen to be the theoretical stress sigma(th) to match that of the Lennard-Jones potential. An alternative and more reasonable model is proposed in this paper. The Maugis model is first extended to that of arbitrary axisymmetric elastic objects with an arbitrary surface adhesive interaction and then applied to the case of a power-law shape function and a step cohesive stress. A continuous transition is found in the extended Maugis-Dugdale model for an arbitrary shape index n. A three-dimensional Johnson-Greenwood adhesion map is constructed. A relation of the identical pull-off force at the rigid limit is required for the approximate and exact models. With this requirement, the stress sigma(0) is found to be k(n)Deltagamma/z(0), where k(n) is a coefficient, Deltagamma the work of adhesion, and z(0) the equilibrium separation. Hence we have sigma(0) = 0.588Deltagamma/z(0), especially for n=2. The prediction of the pull-off forces using this new value shows surprisingly better agreement with the Muller-Yushchenko-Derjaguin transition than that using sigma(th) = 1.026Deltagamma/z(0), and this is true for other values of shape index n. PMID- 17335844 TI - Development and validation of a real time PCR-based bioassay for quantification of neutralizing antibodies against human interferon-beta. AB - There are two commonly employed types of bioassays for the detection of neutralizing antibodies (NAbs) against interferon-beta (IFNbeta): the cytopatic effect assay (CPE), and the MxA (myxovirus resistance protein A) protein assay (MPA). This article describes a bioassay based on the real time PCR measurement of mRNA that results from the induction, in cultured human cells, of the MxA gene by IFNbeta. Serum samples from 104 patients with multiple sclerosis (MS) treated with IFNbeta were tested for NAbs using our real time PCR bioassay. NAbs also were measured in the same specimens by the MPA assay and CPE assay. The calibration range of the real time PCR bioassay is 0.125-30 LU/mL. The range of the intra- and inter-assay variations (coefficients of variation in log(10)) were 4.05% (range 0.88%-7.90%) and 4.42% (range 0.31%-9.15%), respectively. Samples of the three commercial preparations of IFNbeta-1a and -1b were measured showing dose-response curves parallel to that of the NIH reference IFNbeta (mean SD at the midpoint of the dose-response curve=5%). In addition, the assay was robust with respect to number of cells plated (i.e., increasing cell densities from 12x10(3)/well to 384x10(3)/well resulted in 3.03% variability in MxA expression normalized with glyceraldehyde-3 phosphate dehydrogenase). NAbs titers measured were closely comparable to those obtained by the MPA [r(spearman)=0.899; 89% of observed agreements; K=0.779] and the CPE [r(spearman)=0.7899); 86%; K=0.729] assays. Despite the obvious disadvantage of cost, when carried out according to quality assurance guidelines for molecular diagnostics the new MxA gene expression assay (MGA) has significant advantages over the other methods for testing NAbs: it has excellent reliability and reproducibility, and utilizes equipment and methodologies already accessible in many clinical laboratories. PMID- 17335846 TI - Haploinsuffciency for Znf9 in Znf9+/- mice is associated with multiorgan abnormalities resembling myotonic dystrophy. AB - Myotonic dystrophy type 2 is caused by a (CCTG)/(CCUG)n repeat expansion in the first intron of the ZNF9 gene. The pathomechanism for the myotonic dystrophies is not well understood and the role of ZNF9 in myotonic dystrophy type 2 pathogenesis has not been fully clarified. We characterized Znf9+/- mice, in which the expression of Znf9 was significantly decreased, and found that their phenotype reflects many of the features of myotonic dystrophy, including muscle histological morphology, and myotonic discharges and heart conduction abnormalities, shown by electromyography and electrocardiogram analysis, respectively. Znf9 is normally highly expressed in heart and skeletal muscle, where skeletal muscle chloride channel 1 (Clc1) plays an important role. Clc1 expression was dramatically decreased in Znf9+/- mice. Znf9 transgenic mice raised Znf9 and Clc1 expression and rescued the myotonic dystrophy phenotype in Znf9+/- mice. Our results suggest that the Znf9 haploinsufficiency contributes to the myotonic dystrophy phenotype in Znf9+/- mice. PMID- 17335845 TI - Hydrophobic surface burial is the major stability determinant of a flat, single layer beta-sheet. AB - Formation of a flat beta-sheet is a fundamental event in beta-sheet-mediated protein self-assembly. To investigate the contributions of various factors to the stability of flat beta-sheets, we performed extensive alanine-scanning mutagenesis experiments on the single-layer beta-sheet segment of Borrelia outer surface protein A (OspA). This beta-sheet segment consists of beta-strands with highly regular geometries that can serve as a building block for self-assembly. Our Ala-scanning approach is distinct from the conventional host-guest method, in that it introduces only conservative, truncation mutations that should minimize structural perturbation. Our results showed very weak correlation with experimental beta-sheet propensity scales, statistical beta-sheet propensity scales, or cross-strand pairwise correlations. In contrast, our data showed strong positive correlation with the change in buried non-polar surface area. Polar interactions including prominent Glu-Lys cross-strand pairs contribute marginally to the beta-sheet stability. These results were corroborated by results from additional non-Ala mutations. Taken together, these results demonstrate the dominant contribution of non-polar surface burial to flat beta sheet stability even at solvent-exposed positions. The OspA single-layer beta sheet achieves efficient hydrophobic surface burial without forming a hydrophobic core by a strategic placement of a variety of side-chains. These findings further suggest the importance of hydrophobic interactions within a beta-sheet layer in peptide self-assembly. PMID- 17335847 TI - Preprotein transport machineries of yeast mitochondrial outer membrane are not required for Bax-induced release of intermembrane space proteins. AB - The mitochondrial outer membrane contains protein import machineries, the translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM). It has been speculated that TOM or SAM are required for Bax-induced release of intermembrane space (IMS) proteins; however, experimental evidence has been scarce. We used isolated yeast mitochondria as a model system and report that Bax promoted an efficient release of soluble IMS proteins while preproteins were still imported, excluding an unspecific damage of mitochondria. Removal of import receptors by protease treatment did not inhibit the release of IMS proteins by Bax. Yeast mutants of each Tom receptor and the Tom40 channel were not impaired in Bax-induced protein release. We analyzed a large collection of mutants of mitochondrial outer membrane proteins, including SAM, fusion and fission components, but none of these components was required for Bax-induced protein release. The released proteins included complexes up to a size of 230 kDa. We conclude that Bax promotes efficient release of IMS proteins through the outer membrane of yeast mitochondria while the inner membrane remains intact. Inactivation of the known protein import and sorting machineries of the outer membrane does not impair the function of Bax at the mitochondria. PMID- 17335848 TI - Ca2+ versus Mg2+ coordination at the nucleotide-binding site of the sarcoplasmic reticulum Ca2+-ATPase. AB - The recently determined crystal structure of the sarcoplasmic reticulum Ca2+ ATPase (SERCA1a) with a bound ATP analogue (AMPPCP) reveals a compact state, similar to that found in the presence of ADP and aluminium fluoride. However, although the two Ca2+-binding sites in the membrane are known to be occluded in the latter state, in the AMPPCP-bound state the Ca2+-binding sites are not occluded under conditions with physiological levels of Mg2+ and Ca2+. It has been shown that the high concentration (10 mM) of Ca2+ used for crystallization (in the presence of Mg2+) may be responsible for the discrepancy. To determine whether Ca2+ competes with Mg2+ and affects the nucleotide-binding site, we have subjected the AMPPCP and ADP:AlF4- bound forms to crystallographic analysis by anomalous difference Fourier maps, and we have compared AMPPCP-bound forms crystallized in the absence or in the presence of Mg2+. We found that Ca2+ rather than Mg2+ binds together with AMPPCP at the phosphorylation site, whereas the ADP:AlF4- complex is associated with two magnesium ions. These results address the structure of the phosphorylation site before and during phosphoryl transfer. The bound CaAMPPCP nucleotide may correspond to the activated pre-complex, formed immediately before phosphorylation, whereas the Mg(2)ADP:AlF4- transition state complex reflects the preference for Mg2+ in catalysis. In addition, we have identified a phosphatidylcholine lipid molecule bound at the cytosol-membrane interface. PMID- 17335850 TI - Vascular risk factors and intensity of cognitive dysfunction in MCI. AB - Patients with Mild Cognitive Impairment (MCI) have a greater risk of developing dementia than general population. Lots of evidence suggests that cardiovascular risk factors appear more often in the MCI than in general population The aim of this study was to evaluate association between cardiovascular risk factors and intensity of cognitive impairment in MCI patients. We evaluated 24 MCI patients (9 women and 15 men) fulfilling Mayo Clinic Group Criteria. Taking under consideration presence of cardiovascular diseases patients were divided into two groups: first group (n=16) MCI with cardiovascular diseases and second group (n=8) MCI without cardiovascular disorders. Cognitive functions were assessed by neuropsychological tests battery including MMSE, Clock Drawing Test, Trail Making Test (TMT), Verbal Fluency Test with letters FAS, Auditory Verbal Learning Test (AVLT). In the MCI group with vascular risk factors we have found more distinct dysfunction of learning new information, recall and short-term memory than in MCI patients without vascular pathology. In conclusion we may suggest that more distinct cognitive deficit may indicate higher risk of developing dementia, that is why patients with MCI should be under special supervision, with at least annual neuropsychological evaluation. PMID- 17335849 TI - Utility of an abbreviated questionnaire to identify individuals with ADHD at risk for functional impairments. AB - OBJECTIVE: To discern whether a subset of items from the 99-item Current Behavior Scale (CBS) of behaviorally defined Executive Function Deficits (EFDs) in adults with Attention-Deficit/Hyperactivity Disorder (ADHD) can identify a group at risk for poor outcome. METHODS: Subjects were 200 adults with ADHD participating in a family study of ADHD in adults. Factor analysis was used to reduce the number of items in the 99-item CBS. RESULTS: The one factor solution provided eight items with factor loadings above 0.70. This abbreviated set of items was highly correlated with the 99-item CBS (0.91) and was similarly related to functional outcomes compared to the 99-item CBS (average correlation of 0.30 versus 0.32). CONCLUSION: For adults with ADHD, a set of eight empirically-derived from the CBS similarly correlated with negative outcomes compared to the 99-item CBS, raising the possibility of utilization as a mechanism for identification of EFDs in adults with ADHD. PMID- 17335851 TI - Evolutionary stability of egg trading and parceling in simultaneous hermaphrodites: the chalk bass revisited. AB - Several species of simultaneously hermaphroditic seabasses living on coral reefs mate by alternating male and female roles with a partner. This is known as egg trading, one of the classic and most widely cited examples of social reciprocity among animals. Some of the egg-trading seabass species, including the chalk bass, Serranus tortugarum, switch mating roles repeatedly, having subdivided their clutch of eggs into parcels offered to the partner for fertilization. Here we attempt to understand these dynamics as a pair of evolutionary games, modifying some previous approaches to better reflect the biological system. We find that the trading of egg clutches is evolutionarily stable via byproduct mutualism and resistant to invasion by rare individuals that take the male role exclusively. We note why and how parceling may reflect sexual conflict between individuals in the mating pair. We estimate evolutionarily stable parcel numbers and show how they depend on parameter values. Typically, two or more sequential parcel numbers are evolutionarily stable, though the lowest of these yields the highest fitness. Assuming that parcel numbers are adjusted to local conditions, we predict that parcel numbers in nature are inversely related both to mating group density (except at low density) and predation risk. PMID- 17335852 TI - Cellular automaton simulation examining progenitor hierarchy structure effects on mammary ductal carcinoma in situ. AB - A computer simulation is used to model ductal carcinoma in situ, a form of non invasive breast cancer. The simulation uses known histological morphology, cell types, and stochastic cell proliferation to evolve tumorous growth within a duct. The ductal simulation is based on a hybrid cellular automaton design using genetic rules to determine each cell's behavior. The genetic rules are a mutable abstraction that demonstrate genetic heterogeneity in a population. Our goal was to examine the role (if any) that recently discovered mammary stem cell hierarchies play in genetic heterogeneity, DCIS initiation and aggressiveness. Results show that simpler progenitor hierarchies result in greater genetic heterogeneity and evolve DCIS significantly faster. However, the more complex progenitor hierarchy structure was able to sustain the rapid reproduction of a cancer cell population for longer periods of time. PMID- 17335853 TI - Expression and distribution of cholinergic receptors in the human urothelium. AB - The bladder urothelium not only provides a diffusion barrier but it also serves a sensor function and releases signalling molecules that are considered to act in a paracrine and autocrine fashion, e.g. by acetylcholine. Its actions are conferred by two classes of receptors, i.e. G-protein-coupled muscarinic receptors (MR) and ionotropic nicotinic receptors (nAChR). In this study we set out to determine the expression and distribution of all MR subtypes (M1R-M5R) and nAChR alpha-subunits 7, 9 and 10 in the human urothelium by means of RT-PCR and immunohistochemistry, respectively. Real-time RT-PCR revealed a rank order of MR subtype expression of M2R>>M3R=M5R>M4R=M1R. Immunohistochemistry demonstrated differential distribution patterns with M1R being restricted to basal cells, M2R nearly exclusively found in umbrella cells, whereas M3R and M4R were homogenously distributed and M5R was seen in a decreasing gradient from luminal to basal. As for nAChR alpha-subunits, rank order of expression is alpha7>>alpha10>alpha9, and they were observed throughout the urothelium with a gradient decreasing from luminal to basal in intensity. In conclusion, the human urothelium carries multiple cholinergic receptor subtypes, with predominant expression of M2R, M3R and alpha7-nAChR. Their distribution as well as that of the less expressed subtypes is layer specific in the urothelium. In view of the multiplicity of pathways to which different cholinergic receptor subtypes are coupled, we propose that this layer specific distribution serves to stratify cholinergic regulation of human urothelial function. PMID- 17335854 TI - Hydrogen peroxide regulates the cholinergic signal in a concentration dependent manner. AB - The human epidermis holds the full capacity for autocrine synthesis, transport and degradation of acetylcholine as well as the muscarinic (m1-m5) and nicotinic signal transduction in keratinocytes and melanocytes. This cholinergic cascade is severely affected in patients with the depigmentation disorder vitiligo due to accumulation of hydrogen peroxide (H(2)O(2)) in the mM range as shown by in vivo FT-Raman spectroscopy. These high levels can oxidise susceptible amino acid residues such as methionine, tryptophan, cysteine and selenocysteine in the structure of proteins and peptides which in turn can severely affect the function. Here the effect of this reactive oxygen species was followed on the production and degradation of acetylcholine using immunofluorescence, enzyme kinetics, in vivo and in vitro FT-Raman and fluorescence spectroscopy as well as computer modelling. The results showed that both epidermal acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) are target to H(2)O(2)-mediated oxidation of methionine and tryptophan residues close to the catalytic triad, while cholineacetyltransferase (chAT) is not affected. Enzyme kinetics revealed concentration dependent activation/deactivation of both degrading enzymes by H(2)O(2). Oxidation of methionine to methionine sulfoxide was confirmed by FT Raman spectroscopy while oxidation of tryptophan to 5OH-tryptophan was identified by fluorescence spectroscopy. H(2)O(2)-mediated oxidation of both enzymes takes place in acute vitiligo yielding accumulation of acetylcholine in the epidermis of these patients. This process is reversible with a narrowband UVB activated pseudocatalase PC-KUS leading to recovery of epidermal and systemic enzyme activities as well as restoration of the lost skin colour. PMID- 17335855 TI - Disruption of endothelial caveolae is associated with impairment of both NO- as well as EDHF in acetylcholine-induced relaxation depending on their relative contribution in different vascular beds. AB - Caveolae represent an important structural element involved in endothelial signal transduction. The present study was designed to investigate the role of caveolae in endothelium-dependent relaxation of different vascular beds. Caveolae were disrupted by cholesterol depletion with filipin (4x10(-6) g L(-1)) or methyl-beta cyclodextrin (MCD; 1x10(-3) mol L(-1)) and the effect on endothelium-dependent relaxation was studied in rat aorta, small renal arteries and mesenteric arteries in the absence and presence of L-NMMA. The contribution of NO and EDHF, respectively, to total relaxation in response to acetylcholine (ACh) gradually changed from aorta (71.2+/-6.1% and 28.8+/-6.1%), to renal arteries (48.6+/-6.4% and 51.4+/-6.4%) and to mesenteric arteries (9.1+/-4.0% and 90.9+/-4.1%). Electron microscopy confirmed filipin to decrease the number of endothelial caveolae in all vessels studied. Incubation with filipin inhibited endothelium dependent relaxation induced by cumulative doses of ACh (3x10(-9)-10(-4) mol L( 1)) in all three vascular beds. In aorta, treatment with either filipin or MCD only inhibited the NO component, whereas in renal artery both NO and EDHF formation were affected. In contrast, in mesenteric arteries, filipin treatment only reduced EDHF formation. Disruption of endothelial caveolae is associated with the impairment of both NO and EDHF in acetylcholine-induced relaxation. PMID- 17335856 TI - Sediment characteristics and macrofauna distribution along a human-modified inlet in the Gulf of Oristano (Sardinia, Italy). AB - We studied the spatial variability and within-year temporal changes in hydrological features, grain size composition and chemical characteristics of sediments, as well as macrofaunal assemblages, along a heavily modified inlet in the Gulf of Oristano (western Sardinia, Italy). The inlet connects the Cabras lagoon to the gulf through a series of convoluted creeks and man-made structures, including a dam and fish barriers built in the last three decades. Sediments were muddy and mainly composed of the "non-sortable" fraction (i.e., <8 microm particle size) in all four areas investigated: Lagoon, Creeks, Channel and Seaward. Along the inlet, however, the ratio between the <8 microm and the 8-64 microm fractions was highest in Creeks and Channel, between the fish barriers and the dam, suggesting impaired hydrodynamics. Consistently, steep gradients in water salinity, temperature and dissolved oxygen concentrations were found in proximity to the fish barriers. The whole inlet was characterized by a major organic enrichment of sediments, with up to an annual mean of 33.6% of organic matter and 11.7% of total organic carbon in Seaward due to the presence of seagrass leaf litter. Acid-volatile sulphide and chromium-reduced sulphur concentrations were highest throughout the year in Seaward and Lagoon, respectively, with a peak in summer. Consistently, the whole inlet supported low structured macrofaunal assemblages dominated by few opportunist species, with a relatively lower diversity in Lagoon throughout the year and the highest abundances in Seaward in summer. We infer that the presence of artificial structures along the inlet, such as fish barriers and the dam, impair the lagoon gulf hydrodynamics, sediment exchange and animal recruitment and colonization. We suggest that the removal of these structures would favour water renewal in the Cabras lagoon, but would also increase the outflow of organic C-bonding fine particles into the gulf with serious consequences for Posidonia oceanica and Cymodocea nodosa seagrass meadows. We conclude that all possible consequences of such initiatives should be carefully considered before any action is taken. PMID- 17335857 TI - Assessment of biopollution in aquatic ecosystems. AB - The introduction of alien species (AS) in marine environments is a factor of disturbance that can be viewed as a pollution agent. Using basic information on abundance and distribution of alien species, we developed an index that classifies AS impacts on native species, communities, habitats and ecosystem functioning. This method can be used to evaluate impact at five different levels of biopollution, fitting within the existing schemes for water quality assessment. Both spatial and temporal comparisons are possible. The assessments may also be used to evaluate management performance where avoidance measures were necessary and assist in preventing further unwanted introductions. Such assessments made for the same areas over time provide opportunities for measuring change in biopollution. We have tested the method using four different well studied areas within the Baltic Sea (brackish to freshwater environments) for two different times, 20 years apart. Further developments of the scheme may be needed to cover some specific cases and taxonomic groups according to their life history. PMID- 17335858 TI - Understanding the transmission dynamics of respiratory syncytial virus using multiple time series and nested models. AB - The nature and role of re-infection and partial immunity are likely to be important determinants of the transmission dynamics of human respiratory syncytial virus (hRSV). We propose a single model structure that captures four possible host responses to infection and subsequent reinfection: partial susceptibility, altered infection duration, reduced infectiousness and temporary immunity (which might be partial). The magnitude of these responses is determined by four homotopy parameters, and by setting some of these parameters to extreme values we generate a set of eight nested, deterministic transmission models. In order to investigate hRSV transmission dynamics, we applied these models to incidence data from eight international locations. Seasonality is included as cyclic variation in transmission. Parameters associated with the natural history of the infection were assumed to be independent of geographic location, while others, such as those associated with seasonality, were assumed location specific. Models incorporating either of the two extreme assumptions for immunity (none or solid and lifelong) were unable to reproduce the observed dynamics. Model fits with either waning or partial immunity to disease or both were visually comparable. The best fitting structure was a lifelong partial immunity to both disease and infection. Observed patterns were reproduced by stochastic simulations using the parameter values estimated from the deterministic models. PMID- 17335859 TI - [Epidural neurostimulation for chronic pain following abdominal hernia repair]. AB - We report the case of a patient presenting with midline abdominal herniation treated surgically followed by progressively growing abdominal pain resistant to conventional pain treatments. Epidural neurostimulation finally gave satisfactory results. We suggest that epidural neurostimulation can be a valuable tool in treating carefully selected patients with otherwise intractable pain. It is essential to rule out any local complication and to check that conventional analgesia is ineffective, that the psychiatric evaluation is satisfactory and that TENS provides a benefit in pain control. To our knowledge this is to be the first report of epidural neurostimulation for the treatment of chronic pain following repair of midline herniation. PMID- 17335860 TI - Readers' views of a weekly communicable disease bulletin. PMID- 17335861 TI - Adolescent perceptions of violence: formative research findings from a social marketing campaign to reduce violence among middle school youth. AB - OBJECTIVE: To identify the specific barriers and benefits of violent behaviours as noted by middle school youth and to develop a social marketing campaign that attends to the needs and wants of the target audience. STUDY DESIGN: A non experimental, qualitative study design was used to assess youth perceptions of violence in a large, southeast urban school district. METHODS: Using a social marketing approach, a series of in-depth interviews were conducted with middle school youths, to gain an understanding of perceived barriers and benefits of violent behaviours. Additionally, interviews assessed youth preferences for an effective spokesperson for an anti-violence campaign. Qualitative analysis of coded transcripts revealed key themes that were incorporated into a multi-media initiative. RESULTS: Critical themes of the research highlighted that the majority of violence occurs at school, during school hours and most of the youths believed the use of violence was necessary to defend themselves from other peers or to protect family members. Another key finding pertained to adolescent views on violent people; although the majority of respondents reported engaging in violent acts, they did not view themselves as violent. Results were used to inform the development of a social marketing campaign designed to reduce youth violence among middle school students in a large, urban central Florida school district. CONCLUSION: Findings from the formative research led to the creation and pre-testing of five potential campaign brands. The campaign slogan that tested best with the target audience emphasized the choice youth have to either engage in violent behaviour and suffer the consequences or to 'rise above' physical conflict and reap the benefits. PMID- 17335862 TI - Vaccinating behaviour, information, and the dynamics of SIR vaccine preventable diseases. AB - The increasing level of disease control by vaccination jointly with the growing standard of living and health of modern societies could favour the spread of exemption as a "rational" behaviour towards vaccination. Rational exemption implies that families will tend to relate the decision to vaccinate their children to the available information on the state of the disease. Using an SIR model with information dependent vaccination we show that rational exemption might make elimination of the disease an unfeasible task even if coverages as high as 100% are actually reached during epochs of high social alarm. Moreover, we show that rational exemption may also become responsible for the onset of sustained oscillations when the decision to vaccinate also depends on the past history of the disease. PMID- 17335863 TI - Ultrasonic field modeling for immersed components using Gaussian beam superposition. AB - The Gaussian beam (GB) superposition approach can be applied to model ultrasound propagation in complex-structured materials and components. In this article, progress made in extending and applying the Gaussian beam superposition technique to model the beam fields generated by transducers with flat and focused rectangular apertures as well as with circular focused apertures is addressed. The refraction of transducer beam fields through curved surfaces is illustrated by calculation results for beam fields generated in curved components during immersion testing. In particular, the following developments are put forward: (i) the use of individually determined sets of GBs to model transducer beam fields with a number of less than ten beams; (ii) the application of the GB representation of rectangular transducers to focusing probes, as well as to the problem of transmission through interfaces; and (iii) computationally efficient transient modeling by superposition of 'temporally limited' GBs. PMID- 17335864 TI - Diversity of HIV-1 RNA and DNA in breast milk from HIV-1-infected mothers. AB - We compared human immunodeficiency virus type 1 (HIV-1) RNA and DNA populations in the different fractions of breast milk (lactoserum, lipid layer, cell pellet) and between right and left breasts in four HIV-1-infected mothers by analyzing the hypervariable env C2-V5 region. Phylogenetic analyses of the viral quasispecies revealed that RNA populations and DNA populations were clearly distinct and that viral RNA sequences were similar in lipid layer and lactoserum in the milk of 3 out of 4 mothers. Comparison of viral DNA between milk from right and left breast showed a differential distribution of variants in three mothers. In contrast, RNA variants detected from milk of the two breasts were mixed in 3 out of 4 mothers. This study suggests that each mammary gland is subjected to microenvironmental pressure that may differ from the contralateral breast. PMID- 17335865 TI - The effect of CtBP1 binding on the structure of the C-terminal region of adenovirus 12 early region 1A. AB - Adenovirus early region 1A (AdE1A) binds to the C-terminal binding protein 1 (CtBP1) primarily through a highly conserved PXDLS motif located close to its C terminus. Purified synthetic peptides equivalent to this region of AdE1A have been shown to form a series of beta-turns. In this present study the effect of CtBP1 binding on the conformation of C-terminal region of Ad12E1A has been investigated. Using one- and two-dimensional (1)H NMR spectroscopy, the conformation of 20-residue peptides equivalent to amino acids I(241)-V(260) and E(247)-N(266) of Ad12E1A were examined in the absence of CtBP1. Whilst the latter peptide forms a series of beta-turns in its C-terminal half as reported previously, the former peptide is alpha-helical over the region D(243)-Q(253). Upon interaction with CtBP1 the conformation of the backbone in the region (255)PVDLCVK(261) of the Ad12E1A E(247)-N(266) peptide reorganises from a predominately beta-turn to an alpha-helical conformation. This structural isomerisation is characterised by a shift upfield of 0.318 ppm for the delta CH(3) proton resonance of V(256). 2-D NOESY experiments showed new signals in the amide-alpha region which correlate to transferred NOEs from the protein to the peptide residues E(251), V(256) and K(261). In further analyses the contribution of individual amino acids within the sequence (254)VPVDLS(259) was assessed for their importance in determining structure and consequently affinity of the peptide for CtBP. It has been concluded that Ad12E1A residues (255)P-V(260) serve initially as a recognition site for CtBP and then as an anchor through a beta turns-->alpha-helix conformational rearrangement. In addition it has been predicted that regions N-terminal to the PXDLS motif in AdE1As from different virus serotypes and from mammalian proteins form alpha-helices. PMID- 17335866 TI - Enhancement of gene transactivation activity of androgen receptor by hepatitis B virus X protein. AB - Hepatitis B virus (HBV) X protein (HBx) is a regulatory protein that is required for efficient replication of HBV in its natural host. In this report, we demonstrate by co-immunoprecipitation experiments that HBx can physically bind to the androgen receptor (AR), which is a nuclear hormone receptor that is expressed in many different tissues including the liver. This observation is further supported by confocal microscopy, which reveals that HBx can alter the subcellular localization of the AR both in the presence and in the absence of dihydrotestosterone (DHT). Further studies indicate that HBx can enhance the gene transactivation activity of AR by enhancing its DNA binding activity in a DHT dependent manner. However, HBx does not remain associated with AR on the DNA. As AR can regulate the expression of a number of cellular genes, our results raise the possibility that HBV pathogenesis may be mediated in part via the interaction between HBx and AR. PMID- 17335867 TI - Formation of oxidation byproducts from ozonation of wastewater. AB - Disinfection byproduct (DBP) formation in tertiary wastewater was examined after ozonation (O(3)) and advanced oxidation with O(3) and hydrogen peroxide (O(3)/H(2)O(2)). O(3) and O(3)/H(2)O(2) were applied at multiple dosages to investigate DBP formation during coliform disinfection and trace contaminant oxidation. Results showed O(3) provided superior disinfection of fecal and total coliforms compared to O(3)/H(2)O(2). Color, UV absorbance, and SUVA were reduced by O(3) and O(3)/H(2)O(2), offering wastewater utilities a few potential surrogates to monitor disinfection or trace contaminant oxidation. At equivalent O(3) dosages, O(3)/H(2)O(2) produced greater concentrations of assimilable organic carbon (5-52%), aldehydes (31-47%), and carboxylic acids (12-43%) compared to O(3) alone, indicating that organic DBP formation is largely dependent upon hydroxyl radical exposure. Bromate formation occurred when O(3) dosages exceeded the O(3) demand of the wastewater. Bench-scale tests with free chlorine showed O(3) is capable of reducing total organic halide (TOX) formation potential by at least 20%. In summary, O(3) provided superior disinfection compared to O(3)/H(2)O(2) while minimizing DBP concentrations. These are important considerations for water reuse, aquifer storage and recovery, and advanced wastewater treatment applications. PMID- 17335868 TI - Reductive hydrogenation of polycyclic aromatic hydrocarbons catalyzed by metalloporphyrins. AB - The hydrogenation of polycyclic aromatic hydrocarbons (PAHs) (naphthalene, anthracene, and phenanthrene) catalyzed by metalloporphyrins based on cobalt, nickel or iron was studied in aqueous solutions at room temperature and ambient pressure. Nickel porphyrin (P1) activated by nanosized zero-valent iron (nano ZVI) and cobalt porphyrins (P2) and (P4) activated by titanium(III) citrate as the electron donor were demonstrated to be promising catalysts for the reductive hydrogenation of PAHs. In particular, partially saturated di-, tetra-, and octahydrogenated products were obtained for anthracene or phenanthrene using a nickel porphyrin activated by nano-ZVI, while naphthalene was transformed to tetralin. Systems containing cobalt porphyrins activated by titanium(III) citrate exhibited a high selectivity and activity toward hydrogenation of anthracene, producing 9,10-dihydroanthracene. However, no formation of hydrogenated hydrocarbons was observed from naphthalene or phenanthrene using cobalt porphyrins. PMID- 17335869 TI - Dioxin exposure in contaminated sawmill area: the use of molar teeth and bone of bank vole (Clethrionomys glareolus) and field vole (Microtus agrestis) as biomarkers. AB - Developmental disorders of teeth are among the most sensitive targets of polychlorinated dibenzo-p-dioxin and -furan (PCDD/F) exposure. In rats, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) reduces dose-dependently the size of molars, most severely the third lower molars. Dioxins also have effects on developing bone, including altered bone mineral density as well as reduced bending breaking force and stiffness. The aim of this study was to evaluate the use of the third lower molar and long bones as biomarkers of PCDD/F exposure in two wild vole species, the bank vole (Clethrionomys glareolus) and the field vole (Microtus agrestis) collected from a PCDD/F contaminated former sawmill area. Survey of soil and biota of the sawmill area indicated a PCDD/F contamination with a congener profile characteristic for the chlorophenol wood preservative Ky-5. The PCDD/F concentration in the bank vole was notably higher than in the field vole. The third molar of the bank vole was significantly smaller in dioxin-exposed animals compared to control group, while there was no difference between these two groups in the field vole. No significant alterations were observed in bone density and strength in either species except for reduced bending strength of the femur neck in bank vole males exposed to dioxins. Even though the bone changes are among the sensitive endpoints of dioxin-exposure, high variability due to age, size and gender limits their use as biomarkers of wildlife exposure. In conclusion, the size of molar teeth seems to be a sensitive and robust biomarker for PCDD/F exposure in wild bank vole populations and thus worth of further studies. PMID- 17335870 TI - The Caenorhabditis elegans nicotinamidase PNC-1 enhances survival. AB - In yeast, increasing the copy number of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 extends lifespan, which can be inhibited by nicotinamide (Nam), the end-product of Sir2-mediated NAD-breakdown. Furthermore, the yeast pyrazinamidase/nicotinamidase PNC-1 can extend yeast lifespan by converting Nam. In Caenorhabditis elegans (C. elegans), increased dosage of the gene encoding SIR-2.1 also increases lifespan. Here, we report that knockdown of the C. elegans homologue of yeast PNC-1 as well as growing worms on Nam containing medium significantly decreases adult lifespan. Accordingly, increased gene dosage of pnc-1 increases adult survival under conditions of oxidative stress. These data show for the first time the involvement of PNC-1/Nam in the survival of a multicellular organism and may also contribute to our understanding of lifespan regulation in mammals. PMID- 17335871 TI - Spatial and temporal variations of plutonium isotopes (238Pu and 239,240Pu) in sediments off the Rhone River mouth (NW Mediterranean). AB - The dispersion and fate of the Rhone River inputs to the Gulf of Lions (Northwestern Mediterranean Sea) have been studied through the spatial and temporal distributions of plutonium isotopes in continental shelf sediments. Plutonium isotopes ((238)Pu and (239,240)Pu) are appropriate tracers to follow the dispersion of particulate matter due both to their high affinity for particles and their long half-lives. In the Rhone River valley, plutonium isotopes originate from both the weathering of the catchment basin contaminated by global atmospheric fallout, and the liquid effluents released from the Marcoule reprocessing plant since 1961. This work presents a first detailed study on (238)Pu and (239,240)Pu distributions in sediments from the Rhone prodelta to the adjacent continental shelf, since the decommissioning of Marcoule in 1997. The vertical distribution of Pu isotopes has been analysed in a 4.75 m long core sampled in 2001 at the Rhone mouth. Despite this length, plutonium is found at the last 10 cm, manifesting the high sedimentation rate of the prodeltaic area and its ability for trapping fine-grained sediments and associated contaminants. The highest (238)Pu and (239,240)Pu concentrations reached 1.26 and 5.97 Bq kg( 1) respectively and were found within the layer 280-290 cm. The (238)Pu/(239,240)Pu activity ratios (AR) demonstrated an efficient and huge trapping of the Pu isotopes derived from Marcoule. The fresh sediments, located on the top of the core, show lower plutonium activity concentrations and lower (238)Pu/(239,240)Pu ratios. This decrease is in close relation with the shut down of the Marcoule reprocessing plant in 1997. In 2001, plutonium isotopes were also analysed in 21 surface sediments located offshore and concentrations ranged from 0.03 to 0.17 Bq kg(-1) for (238)Pu and from 0.33 to 1.72 Bq kg(-1) for (239,240)Pu. The (238)Pu/(239,240)Pu AR ranged from 0.24 close to the river mouth to 0.06 southwards, indicating the decreasing influence of the Marcoule releases (global fallout AR 0.03-0.05 and Marcoule AR 0.30). This is in good agreement with the main direction spread of the Rhone River plume and the bottom current. This dataset has been compared to those obtained in the same area in 1984 and 1990 in order to follow the time trend in Pu concentrations. This comparison highlights the decrease with time in plutonium concentrations close to the Rhone River mouth, but further away this reduction is not so evident. PMID- 17335872 TI - Long-term effects of rainforest disturbance on the nutrient composition of throughfall, organic layer percolate and soil solution at Mt. Kilimanjaro. AB - At the lower parts of the forest belt at Mt. Kilimanjaro, selective logging has led to a mosaic of mature forest, old secondary forests ( approximately 60 years), and old clearings ( approximately 10 years) covered by shrub vegetation. These variations in the vegetation are reflected by differences in nutrient leaching from the canopy and in both amount and quality of litter reaching the ground, thereby also influencing mineralization rates and the composition of seepage water in litter percolate and soil solution. The aim of this study was to investigate how above- and belowground nutrient dynamics vary between regeneration stages, and if forest regeneration at the clearings is hampered by a deterioration of abiotic site conditions. K, Mg, Ca, Na and N compounds were analysed in rainfall, throughfall, organic layer percolate and the soil solution to a depth of 1.00 m at three clearings, three secondary forest and four mature forest sites. Element fluxes via throughfall showed only small variations among regeneration stages except for K and NO(3)-N. With 57-83 kg ha(-1) a(-1)and 2.6 4.1 kg ha(-1) a(-1) respectively, K and NO(3)-N fluxes via throughfall were significantly higher at the clearings than at the mature forest sites (32-37 and 0.7-1.0 kg ha(-1) a(-1) for K and NO(3)-N). In organic layer percolate and in soil solution at 0.15-m soil depth, concentrations of K, Mg, Ca and N were highest at the clearings. In the organic layer percolate, median K concentrations were e.g. 7.4 mg l(-1) for the clearings but only 1.4 mg l(-1) for the mature forests, and for NO(3)-N, median concentrations were 3.1 mg l(-1) for the clearings but only 0.92 mg l(-1) for the mature forest sites. Still, differences in annual means between clearings and mature forests were not always significant due to a high variability within the clearings. With the exception of NO(3)-N, belowground nutrient concentrations in secondary forests ranged between concentrations in mature forests and clearings. Vegetation type-specific differences decreased with increasing soil depths in the soil solution. Overall, the opening of the forest led to a higher spatial and seasonal variation of nutrient concentrations in the seepage water. These results suggest differences in both mineralization rates and in nutrient budgeting at different regeneration stages. Since nutrient availability was highest at the clearings and no compaction of the soil was observed, deterioration of soil properties did not seem to be the main reason for the impeded regeneration on the clearings. PMID- 17335873 TI - Functional transcriptomics: an experimental basis for understanding the systems biology for cancer cells. PMID- 17335874 TI - New insights into creatine function and synthesis. PMID- 17335875 TI - 3-D culture in synthetic extracellular matrices: new tissue models for drug toxicology and cancer drug discovery. PMID- 17335876 TI - Ectopic expression of L-plastin in human tumor cells: diagnostic and therapeutic implications. PMID- 17335877 TI - Genetic insights into the hypoxia-inducible factor (HIF) pathway. PMID- 17335878 TI - Nuclear inositide signaling: an appraisal of phospholipase C beta 1 behavior in myelodysplastic and leukemia cells. PMID- 17335879 TI - Phosphatidylinositol transfer proteins and functional specification of lipid signaling pools. PMID- 17335880 TI - Are self-collected samples comparable to physician-collected cervical specimens for human papillomavirus DNA testing? A systematic review and meta-analysis. AB - OBJECTIVE: To compare the detection rate of genital human papillomavirus (HPV) infection in self- and physician-obtained samples. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Studies published between 1966 and November 2005 identified through Medline and Embase that compared both sampling methods. MAIN OUTCOME MEASURES: We calculated the concordance and kappa statistic between physician- and self-sampling and the difference between proportions of HPV positive samples. Weighted averages were reported with 95% confidence intervals (CI) using a random-effects model. RESULTS: Eighteen studies (5441 participants) were included that evaluated broad HPV type categories, 10 (3688 patients) that of high-risk (HR) HPV and three (530) that of low-risk (LR) HPV. A high level of concordance of 0.87 (95%CI, 0.82 to 0.91) between self- and physician-sampling was obtained for detection of HPV DNA (kappa 0.66, 95%CI, 0.56 to 0.76). The prevalence difference of HPV DNA between sampling methods was -0.5 (95%CI, -2.8 to 1.8). Results were similar when restricting the analysis to HR-HPV but the prevalence of LR-HPV types was higher in self-collected samples. CONCLUSION: Self sampling was as sensitive as physician-obtained sampling to detect HR-HPV or HPV DNA. Self-sampling may be a suitable alternative method for studies on HPV transmission and vaccine trials. PMID- 17335881 TI - Metastatic colorectal adenocarcinoma involving the ovary with elevated serum CA125: a potential diagnostic pitfall. AB - OBJECTIVES: Elevated serum levels of CA125 are observed not only in association with primary ovarian epithelial neoplasms but also in a variety of other clinical settings, including ovarian involvement by metastatic disease. There is considerable overlap in gross and histologic features between primary ovarian tumors and metastatic colorectal adenocarcinoma, which can make diagnosis particularly challenging in the setting of an increased CA125 level. The aims of this study were to determine how frequently serum CA125 is elevated in women with ovarian involvement by metastatic colorectal adenocarcinoma and to compare the features of cases with and without associated elevations of serum CA125. METHODS: Eighty-nine cases of histologically confirmed ovarian involvement by metastatic colorectal adenocarcinoma were identified by retrospective review. Clinicopathologic data were analyzed, including preoperative serum CA125 level (available in 42 cases). Features of cases with an associated increase in serum CA125 were compared with those of cases with no such elevation. RESULTS: Twenty nine patients had an elevated serum CA125 level (>35 U/mL) preoperatively (range 39.0-556.3, median 143.0, mean 199.1). Thirteen patients had a serum CA125 level within the reference range, while forty-seven patients had no preoperative testing for serum CA125. Clinical, gross, and histologic features of cases with an associated increase in serum CA125 were generally similar to those of cases with a non-elevated serum CA125 concentration. In three cases, the tumor was initially diagnosed as an ovarian primary. CONCLUSIONS: At least 32.6% of women with ovarian involvement by metastatic colorectal adenocarcinoma have an elevated serum CA125 level prior to oophorectomy. Such cases do not differ significantly from cases lacking such an association with respect to a variety of clinicopathologic features. The possibility of metastasis from a colorectal carcinoma merits consideration in the formation of the differential diagnosis for a woman with an adnexal mass and elevated serum CA125, even in the absence of an established history of gastrointestinal malignancy. PMID- 17335882 TI - Causes of death in hyper-IgE syndrome. AB - BACKGROUND: Hyper-IgE syndrome (HIES) is characterized by recurrent pyogenic infections, eczema, increased serum IgE levels, and a variety of connective tissue and skeletal system abnormalities. Little has been published regarding the causes of death in these patients or pathologic findings. OBJECTIVE: To identify the cause of death in patients with HIES and to describe pathologic findings in fatal HIES. METHODS: We reviewed the medical records and autopsy slides of 6 patients with HIES with autopsies performed at our institution. RESULTS: All 6 patients with HIES were women and ranged in age from 24 to 40 years. All patients had a history of cystic lung disease and had pneumonia at the time of death, with Pseudomonas aeruginosa and fungal organisms predominating. Pulmonary fungal vascular invasion with fatal hemorrhage was observed in 3 patients, and metastatic fungal disease to the brain was observed in 2 patients caused by Aspergillus fumigatus and Scedosporium prolificans. Four patients had evidence of renal tubular injury, which was likely from amphotericin B toxicity; 3 patients had glomerulosclerosis; and 1 patient had 2 kidney angiomyolipomas. CONCLUSIONS: Our series highlights the important role Pseudomonas and Aspergillus species play in patients with HIES with cystic lung disease. Intensified antifungal and gram negative bacterial prophylaxis need evaluation as possible strategies to prevent these infectious complications in patients with cystic lung disease. CLINICAL IMPLICATIONS: Fungal and Pseudomonas infection of cystic lung disease in HIES may be life threatening, and the proper management and prevention of these infections need continued investigation. PMID- 17335883 TI - FCERIA gene promoter polymorphisms: lack of association with aspirin hypersensitivity in whites. PMID- 17335884 TI - Expression of activation markers on basophils in a controlled model of anaphylaxis. AB - BACKGROUND: Anaphylaxis has variable clinical presentations and lacks reliable biomarkers. Expression of activation markers on basophils has been useful in assessing sensitization in IgE-mediated diseases but has not been examined in vivo in anaphylaxis. OBJECTIVE: The study's goals were to assess the baseline expression of activation markers on basophils in individuals with a sting reaction history, the degree of change in expression of these markers after intentional sting challenge, and the relationship between in vitro and in vivo activation marker expression. METHODS: Patients allergic to insect venom were enrolled and grouped by clinical category defined by a history of a systemic or large local reaction and use of venom immunotherapy. Blood was collected before and after sting challenge. Enriched basophils were analyzed for activation marker expression. In select subjects, basophils were examined after in vitro stimulation with insect venom for activation marker expression and histamine release. RESULTS: Of 35 sting-challenge participants, 21 provided adequate samples for analysis. Pre-sting basophil CD63 expression was significantly higher in systemic reactors on immunotherapy. Following sting challenge, the rise in basophil CD69 expression and CD203c was significantly higher in systemic reactors on immunotherapy. Levels of activation markers on basophils were greater after in vitro venom stimulation than after in vivo challenge. CONCLUSION: Broader shifts in expression of basophil activation markers after in vivo challenge occurred among subjects with a history of in vivo systemic anaphylaxis despite venom immunotherapy. CLINICAL IMPLICATIONS: Basophil activation markers may be potential biomarkers for anaphylaxis. PMID- 17335885 TI - Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: implications for systemic disease and immunosenescence. AB - BACKGROUND: Dendritic cells (DCs) play a key role as antigen-presenting cells in the immune system. There is growing evidence that the redox equilibrium of these cells influences their ability to induce T-cell activation and to regulate the polarity of the immune response. This could affect the outcome of the immune response during systemic diseases and aging. OBJECTIVE: Our aim was to elucidate the mechanism by which the redox equilibrium of antigen-presenting DCs affects the delayed-type hypersensitivity (DTH) response during experimental modification of glutathione levels, as well as during aging. METHODS: We looked at the effect of glutathione depletion by diethyl maleate in DCs as well as during systemic administration on the DTH response to the contact-sensitizing antigens, oxazolone, and 2,4-dinitro-1-fluorobenzene. We also determined whether glutathione repletion with N-acetyl cysteine could influence the decline of the DTH response in aged mice. RESULTS: Glutathione depletion in bone marrow-derived DCs interfered in their ability to mount a DTH response on adoptive transfer into recipient mice. Glutathione depletion interfered in IL-12 production and costimulatory receptor expression in DCs, leading to decreased IFN-gamma production in the skin of recipient mice. Systemic diethyl maleate treatment exerted similar effects on the DTH response and IFN-gamma production, whereas N acetyl cysteine administration reversed the decline of the DTH response in aged animals. CONCLUSION: Glutathione depletion downregulates T(H)1 immunity through a perturbation of DC maturation and IL-12 production. CLINICAL IMPLICATIONS: These data show that the induction of oxidative stress in the immune system, under disease conditions and aging, interferes in T(H)1 immunity. PMID- 17335886 TI - Recombinant allergens for immunotherapy. AB - Recombinant allergens can be produced as defined molecules in consistent quality and unlimited amounts according to the corresponding DNA template. Furthermore, they can be modified to reduce their allergenic activity and to foster certain advantageous immunologic properties. Recombinant allergens equaling the natural allergens are available for diagnostic and therapeutic purposes, and modified versions have been developed with the aim to to reduce IgE-mediated side effects during immunotherapy. First injection immunotherapy trials conducted with recombinant vaccines for birch pollen and grass pollen allergy show that recombinant allergen-based immunotherapy has vaccination characteristics and is clinically effective. The obtained results hold promise that recombinant allergen based immunotherapy will improve current immunotherapy practice and may open possibilities for new treatment strategies and possibly even for prophylactic vaccination. PMID- 17335887 TI - IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease. AB - BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a systemic refractory autoimmune disease. IL-23 has been thought to play a critical role in autoimmune disease through inducing the development of IL-17-producing CD4(+) T cells. OBJECTIVE: To investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in patients with VKH disease. METHODS: Blood samples were taken from 25 patients with VKH disease and 16 healthy controls. Peripheral blood mononuclear cells (PBMCs) were subjected to analysis of IL-23p19 mRNA and IL-23 protein expression using RT-PCR and ELISA, respectively. The IL-17 levels in the supernatants of PBMCs and CD4(+) T cells cultured in the absence or presence of recombinant (r)IL-23, rIL-12, or anti-IFN-gamma were determined by ELISA. RESULTS: The patients with VKH disease with active uveitis showed an elevated level of IL-23p19 mRNA in PBMCs, higher IL-23 in the serum and supernatants of PBMCs, and increased production of IL-17 by polyclonally stimulated PBMCs and CD4(+) T cells. Recombinant IL-23 significantly enhanced IL 17 production, whereas rIL-12 and IFN-gamma inhibited IL-17 production. More importantly, IL-17 production was significantly increased in patients with active uveitis in the presence of rIL-23. Both rIL-23 and rIL-12 enhanced IFN-gamma production. CONCLUSION: The results suggest that IL-23-stimulated production of IL-17 by CD4(+) T cells may be responsible for the development of uveitis seen in patients with VKH disease. CLINICAL IMPLICATIONS: This study provides a new insight into the mechanism involved in the development of VKH disease. PMID- 17335888 TI - Potential of an altered peptide ligand of lipocalin allergen Bos d 2 for peptide immunotherapy. AB - BACKGROUND: Peptide immunotherapy is a promising alternative for treating allergic diseases. One way to enhance the efficacy of peptide immunotherapy is to use altered peptide ligands (APLs) that contain amino acid substitutions compared with the natural peptide. OBJECTIVE: To evaluate the potential of an APL of the immunodominant epitope of lipocalin allergen Bos d 2 for peptide immunotherapy. METHODS: Peripheral blood CD4(+) T-cell responses of 8 HLA-DR4-positive subjects to the natural ligand of Bos d 2 (p127-142) or to an APL (pN135D) were analyzed by MHC class II tetramer staining after in vitro expansion with the peptides. Long-term T-cell lines (TCLs) were induced with the peptides, and the cytokine production, cross-reactivity, and T-cell receptor Vbeta subtype expression of the TCLs were analyzed. RESULTS: CD4(+) T cells specific for both p127-142 and pN135D were readily detected in peripheral blood after a single in vitro stimulation. Whereas the TCLs induced with p127-142 were T(H)2/T(H)0-deviated, those induced with pN135D were T(H)1/T(H)0-deviated and highly cross-reactive with p127-142. Moreover, the pN135D-induced TCLs appeared to use a broader repertoire of T-cell receptor Vbeta subtypes than those induced with p127-142. CONCLUSION: An APL of an immunodominant allergen epitope was able to induce a novel T(H)1-deviated T cell population cross-reactive with the natural epitope in vitro. This cell population could have a therapeutic immunomodulatory function in vivo through bystander suppression. CLINICAL IMPLICATIONS: These results support the idea that altered peptide ligands may be used to enhance the efficacy of peptide immunotherapy. PMID- 17335889 TI - Binge drinking is a problem that cannot be ignored. PMID- 17335890 TI - Adolescents' physical activity in relation to family income and parents' education. AB - OBJECTIVE: Regular physical activity provides young people with important physical, mental, and social health benefits. This study aimed to evaluate the relationship of family income and parents' level of education with physical activity in Finnish adolescents. METHOD: The study population consisted of the Northern Finland Birth Cohort 1986, including 5457 boys and girls aged 15-16 years, and their parents who responded to a postal inquiry in 2001-2002. The associations between social background and adolescents' physical activity were analyzed in 2005 using cross-tabulation and multivariate logistic regression. RESULTS: High parental education was associated with adolescents being physically active. In boys father's high educational level (OR: 0.56; CI: 0.33, 0.95), and in girls both mother's (OR: 0.55; CI: 0.31, 0.98) and father's (OR: 0.35; CI: 0.20, 0.61) high educational levels were related to the least time spent watching TV. High family income was associated with being an active sports club member in boys (OR: 2.43; CI: 1.74, 3.40) and girls (OR: 2.67; CI: 1.81, 3.94). Adolescents' participation in different types of physical activity varied according to family income. CONCLUSIONS: Economic support for youth sports and informing parents on ways to encourage adolescents' physical activity are recommended to ensure equal opportunities for youths to participate in different physical activities. PMID- 17335891 TI - Long-term effects of a playground markings and physical structures on children's recess physical activity levels. AB - OBJECTIVE: The aim of the study was to investigate the impact of a playground redesign intervention across time on children's recess physical activity levels using combined physical activity measures and to evaluate the potential influence of covariates on the intervention effect. METHOD: Fifteen schools located in areas of high deprivation in one large city in England each received 20,000 pounds through a national 10 million pounds Sporting Playgrounds Initiative to redesign the playground environment based on a multicolored zonal design. Eleven schools served as matched socioeconomic controls. Physical activity levels during recess were quantified using heart rate telemetry and accelerometry at baseline, 6 weeks and 6 months following the playground redesign intervention. Data were collected between July 2003 and January 2005 and analyzed using multilevel modeling. RESULTS: Statistically significant intervention effects were found across time for moderate-to-vigorous and vigorous physical activity assessed using both heart rate and accelerometry. CONCLUSIONS: The results suggest that a playground redesign, which utilizes multicolor playground markings and physical structures, is a suitable stimulus for increasing children's school recess physical activity levels. PMID- 17335892 TI - Temperature and urea induced conformational changes of the histidine kinases from Mycobacterium tuberculosis. AB - A unique three protein two-component system is present in Mycobacterium tuberculosis comprising of two histidine kinases (Rv0600c/HK1 and Rv0601c/HK2) and a response regulator (Rv0602c/TcrA). The HK2 is a novel HPt-mono domain protein absent in other bacteria. We present here the temperature and urea induced denaturation study of HK1 and HK2 using circular dichroism and fluorescence spectroscopy. HK1 and HK2 are thermally quite stable. Thermal transition of HK1 is a two-state process and that of HK2 is a three-state process. Urea denaturation of HK1 and HK2 is a three-state and two-state process, respectively. The DeltaG degrees of the two transitions during urea induced unfolding of HK1 is 4.76+/-0.6 kcal/mol and -7.11+/-0.8 kcal/mol. Unfolding of HK2 in presence of urea has DeltaG degrees of 4.766+/-0.5 kcal/mol. The intrinsic fluorescence study of HK2 unfolding implies flexibility of proline rich loop in the tryptophan bearing HAMP domain. PMID- 17335894 TI - The attenuation of experimental lung metastasis by a bile acid acylated-heparin derivative. AB - The inhibitory efficacies of new bile acid acylated-heparin derivative (heparin DOCA) were evaluated on experimental lung metastasis. We evaluated the effect of heparin-DOCA on intercellular interactions including those between B16F10 and thrombin-activated platelets and TNF-alpha-activated HUVECs, and between B16F10 and immobilized mouse P-selectin. In addition, the inhibitory effects of heparin DOCA on adhesion and invasion of B16F10 to Matrigel were studied. In an animal mouse study, the blood clot formation and the retention of red fluorescence protein (RFP)-B16F10 in lungs were assessed after heparin-DOCA and RFP-B16F10 intravenous administration. Furthermore, we investigated the anti-metastatic effect of heparin-DOCA against lung metastasis induced by B16F10 and SCC7. Heparin-DOCA inhibited intercellular interactions between B16F10 and activated platelets or activated HUVECs by blocking P- and E-selectin-mediated interactions. Moreover, it reduced adhesion and invasion of B16F10 to ECM, thereby affecting the reduction of early retention of B16F10 in the lung. Heparin DOCA attenuated lung colony formation on the surfaces and in interior of the lung, and attenuated metastasis by B16F10 and SCC7. These results suggest that heparin-DOCA may have potentials as therapeutic agent that prevents tumor metastasis and progression. PMID- 17335895 TI - Biocompatibility of nanoporous alumina membranes for immunoisolation. AB - Cellular immunoisolation using semi-permeable barriers has been investigated over the past several decades as a promising treatment approach for diseases such as Parkinson's, Alzheimer's, and Type 1 diabetes. Typically, polymeric membranes are used for immunoisolation applications; however, recent advances in technology have led to the development of more robust membranes that are able to more completely meet the requirements for a successful immunoisolation device, including well controlled pore size, chemical and mechanical stability, nonbiodegradability, and biocompatibility with both the graft tissue as well as the host. It has been shown previously that nanoporous alumina biocapsules can act effectively as immunoisolation devices, and support the viability and functionality of encapsulated beta cells. The aim of this investigation was to assess the biocompatibility of the material with host tissue. The cytotoxicity of the capsule, as well as its ability to activate complement and inflammation was studied. Further, the effects of poly(ethylene glycol) (PEG) modification on the tissue response to implanted capsules were studied. Our results have shown that the device is nontoxic and does not induce significant complement activation. Further, in vivo work has demonstrated that implantation of these capsules into the peritoneal cavity of rats induces a transient inflammatory response, and that PEG is useful in minimizing the host response to the material. PMID- 17335896 TI - Assessment of bone ingrowth into porous biomaterials using MICRO-CT. AB - The three-dimensional (3D) structure and architecture of biomaterial scaffolds play a critical role in bone formation as they affect the functionality of the tissue-engineered constructs. Assessment techniques for scaffold design and their efficacy in bone ingrowth studies require an ability to accurately quantify the 3D structure of the scaffold and an ability to visualize the bone regenerative processes within the scaffold structure. In this paper, a 3D micro-CT imaging and analysis study of bone ingrowth into tissue-engineered scaffold materials is described. Seven specimens are studied in this paper; a set of three specimens with a cellular structure, varying pore size and implant material, and a set of four scaffolds with two different scaffold designs investigated at early (4 weeks) and late (12 weeks) explantation times. The difficulty in accurately phase separating the multiple phases within a scaffold undergoing bone regeneration is first highlighted. A sophisticated three-phase segmentation approach is implemented to develop high-quality phase separation with minimal artifacts. A number of structural characteristics and bone ingrowth characteristics of the scaffolds are quantitatively measured on the phase separated images. Porosity, pore size distributions, pore constriction sizes, and pore topology are measured on the original pore phase of the scaffold volumes. The distribution of bone ingrowth into the scaffold pore volume is also measured. For early explanted specimens we observe that bone ingrowth occurs primarily at the periphery of the scaffold with a constant decrease in bone mineralization into the scaffold volume. Pore size distributions defined by both the local pore geometry and by the largest accessible pore show distinctly different behavior. The accessible pore size is strongly correlated to bone ingrowth. In the specimens studied a strong enhancement of bone ingrowth is observed for pore diameters>100 microm. Little difference in bone ingrowth is measured with different scaffold design. This result illustrates the benefits of microtomography for analyzing the 3D structure of scaffolds and the resultant bone ingrowth. PMID- 17335897 TI - Short-term biocompatibility of biphasic nanocolloids with potential use as anisotropic imaging probes. AB - Advances in nanotechnology, in particular the development of novel types of nanoparticles, will result in advanced tools for biomedical research and clinical practice. One exciting aspect of future nanomaterial research will be the possibility to combine therapy and imaging in multifunctional nanoparticle designs. In this context, anisotropic particles with subcellular dimensions may offer so far unattainable capabilities, because they could provide access to directional information with respect to nanoparticle-cell interactions. We have recently developed an electrified jetting process, which can produce water-stable polymer particles with two distinct phases. To address the first critical hurdle towards the application of these biphasic nanocolloids as imaging probes, short term biocompatibility was evaluated using model cell culture systems. Exposure of human endothelial cells and murine fibroblasts to biphasic nanocolloids made of 0.5% polyacrylic acid and 4.5% poly(acrylamide-co-acrylic acid) did not affect cell proliferation as determined by a colorimetric proliferation assay. Moreover, double staining with Annexin V and propidium iodide and subsequent flow cytometric analysis indicated high cell viability, although slightly decreased viability was observed at the highest dose tested (1mg particles/10(6) seeded cells). Particle internalization as well as surface binding occurred simultaneously for both cell types, as evidenced by confocal laser scanning microscopy. Taken together, these results suggest excellent short-term biocompatibility in physiological systems for wide concentration ranges of the biphasic nanocolloids and open possibilities for future work investigating receptor- or surface marker-mediated targeting. PMID- 17335898 TI - Multivariate analysis strategies for processing ToF-SIMS images of biomaterials. AB - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a hyperspectral imaging technique. Each pixel in a two-dimensional ToF-SIMS image (or each voxel in a three-dimensional (3-D) ToF-SIMS image) contains a full mass spectrum. Thus, multivariate analysis methods are being increasingly used to process biomaterial ToF-SIMS images so the maximum amount of information can be extracted from the images. This study examines the use of principal component analysis (PCA) and maximum autocorrelation factors (MAF) on four different ToF-SIMS images. These images were selected because they represent significant challenges for biomedical ToF-SIMS image processing (topographical features, low count rates, surface contaminants, etc.). With PCA four different types of scaling methods (auto, root mean, filter, and shift variance scaling) were used. The effect of two preprocessing methods (normalization and mean centering) was also examined for both PCA and MAF. The more computational intense MAF provided the best results for all the images investigated in this study, doing the best job of reducing the number of variables required to describe the image, enhancing image contrast and recovering key spectral features. MAF was particularly good at identifying subtle features that were often lost in PCA and impossible to visualize in single peak images. However, the combination of PCA with either root mean or shift variance scaling provided similar results to MAF. Thus, these combinations offer promising alternatives to MAF for working with large data sets encountered in 3-D imaging. Also, the new method of filter scaling is promising for processing low count rate images with salt and pepper noise. Normalization proved an important tool for deconvoluting chemical effects from topographic and/or matrix effects. Mean centering aided in reducing the dimensionality of the data, but in one case resulted in a loss of information. PMID- 17335899 TI - Differential regulation of adrenomedullin gene expression in the fundic and pyloric regions of the rat stomach during acute and chronic starvation. AB - Adrenomedullin (AM) has been shown to be present in the stomach but the role of gastric AM is obscure. To investigate the effects of starvation on AM in the stomach, we studied the changes in gene expression of preproadrenomedullin (preproAM) and AM receptors by reverse transcription-polymerase chain reaction (RT-PCR), and tissue AM concentrations by radioimmunoassay (RIA) in the fundus and pylorus of the stomach of rats subjected to either acute (1-day) or chronic (4-day) starvation. An up-regulation of preproAM gene expression was observed in the fundus after acute starvation, and in the pylorus after chronic starvation. Immunoreactive AM (ir-AM) levels were increased in both fundus and pylorus after chronic starvation. In addition, marked reductions in the gene expression of fundic calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP) 3 as well as the pyloric CRLR and RAMP2 were observed in the chronically starved rats. The present study suggests that the gene expression of preproadrenomedullin mRNA is differentially regulated by starvation in the different parts of the stomach. PMID- 17335900 TI - Breaking the cycle of intergenerational abuse: the long-term impact of a residential care program. AB - OBJECTIVE: The number of youth in residential care programs who have been abused is high. The relationship between childhood abuse victimization and adult intimate partner violence (IPV) is well documented. This study compared the rates of IPV 16 years after individuals had participated in a long-term residential care program with individuals accepted to the program who did not participate. The IPV rates for these two groups were also compared to national normative data. METHOD: Information on adult functional outcomes was obtained from former residential care and comparison youth via a confidential survey that was administered either by telephone or by mail. Analysis was limited to respondents who were currently married or involved in a marriage-like relationship (n=131; 92% male). RESULTS: The IPV rates for the sample were 9.3% for those who stayed in the residential program less than 18 months and 6.5% for those who stayed more than 18 months, neither of which were significantly different from the national norm of 8.4%. The IPV rate for the comparison group was 26.1%, which was significantly higher than the national norm. Regardless of length of program stay, respondents who were maltreated in childhood had a 14.5% IPV rate, which was significantly lower than the estimated 36-42% rate projected for individuals with similar backgrounds. CONCLUSION: We conclude that time spent in a treatment oriented residential care program was associated with lower adult IPV rates. Specifically, the skills taught in a long-term, treatment-based residential program (e.g., healthy interpersonal relationships, self-government) may have a long-term beneficial impact for adolescents at high risk of adult IPV. PMID- 17335901 TI - Biomarkers of metals exposure in fish from lead-zinc mining areas of southeastern Missouri, USA. AB - The potential effects of proposed lead-zinc mining in an ecologically sensitive area were assessed by studying a nearby mining district that has been exploited for about 30 y under contemporary environmental regulations and with modern technology. Blood and liver samples representing fish of three species (largescale stoneroller, Campostoma oligolepis, n=91; longear sunfish, Lepomis megalotis, n=105; and northern hog sucker, Hypentelium nigricans, n=20) from 16 sites representing a range of conditions relative to mining activities were collected. Samples were analyzed for metals (also reported in a companion paper) and for biomarkers of metals exposure [erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) activity; concentrations of zinc protoporphyrin (ZPP), iron, and hemoglobin (Hb) in blood; and hepatic metallothionein (MT) gene expression and lipid peroxidation]. Blood lead concentrations were significantly higher and ALA-D activity significantly lower in all species at sites nearest to active lead zinc mines and in a stream contaminated by historical mining than at reference or downstream sites. ALA-D activity was also negatively correlated with blood lead concentrations in all three species but not with other metals. Iron and Hb concentrations were positively correlated in all three species, but were not correlated with any other metals in blood or liver in any species. MT gene expression was positively correlated with liver zinc concentrations, but neither MT nor lipid peroxidase differences among fish grouped according to lead concentrations were statistically significant. ZPP was not detected by hematofluorometry in most fish, but fish with detectable ZPP were from sites affected by mining. Collectively, these results confirm that metals are released to streams from active lead-zinc mining sites and are accumulated by fish. PMID- 17335902 TI - Induction of humoral and cellular immunity against latent HSV-1 infections by DNA immunization in BALB/c mice. AB - Previously, we have reported that the injection of an expression vector containing Herpes simplex virus (HSV) Glycoprotein D-1 (gD-1) generated a significant antibody response in mice and protected them against HSV lethal challenge. We tested its potential to induce antibody and cell mediated immune responses in latently infected mice. Positive control group (KOS) and HSV gD-1 vaccinated mice demonstrated protection against a lethal ocularly challenge of 10(5.5) plaque-forming units (pfu)/eye of wild HSV-1 versus negative control groups. For neutralizing antibody titers, delayed-type hypersensitivity (DTH), lymphocyte proliferation responses, clinical evaluation and survival following lethal challenge, no considerable difference was observed between mice vaccinated with DNA plasmid and those vaccinated with KOS. KOS-vaccinated mice demonstrated the ability to completely prevent latency whereas DNA vaccinated group showed some degree of protection and displayed less latency than negative control groups and had considerably high levels of IFN-gamma and strong CTL responses versus negative control groups. It can be concluded that although immunization with the DNA vaccine is more effective in both protecting mice and induction of immune response, however it could not completely block the latent infection in sensory nerves. PMID- 17335903 TI - The interaction of C-Rel with C/EBPbeta enhances C/EBPbeta binding to the C reactive protein gene promoter. AB - C-reactive protein (CRP) is a plasma protein primarily synthesized in the liver following inflammatory stimuli as part of the acute phase response. Expression of CRP is tightly regulated in hepatocytes. Normally very little CRP mRNA is transcribed, but inflammatory stimuli are followed by a dramatic increase in mRNA synthesis and accumulation. Interleukins -6 and 1 (IL-6 and IL-1) are believed to be the major cytokines responsible for induction of acute phase protein biosynthesis. We previously demonstrated that in vivo c-Rel plays a novel regulatory role in that it appears to be in complex with C/EBPbeta when C/EBPbeta is bound to the CRP gene promoter following cytokine stimulation, but is not itself bound to DNA. In this study we found that recombinant c-Rel((1-300)) (truncated c-Rel protein missing the transactivation domain) increased the affinity of recombinant C/EBPbeta for a CRP-derived C/EBP site (-53) at least 10 fold. This effect was independent of a previously described p50 binding site at 43 and of binding of c-Rel to DNA. C/EBPbeta and c-Rel((1-300)) were found to physically interact in solution, and overexpression of c-Rel (either full length or truncated (1-300)) in the presence of overexpressed C/EBPbeta stimulated CRP transcription. We conclude that c-Rel((1-300)) binding to C/EBPbeta increases the affinity of C/EBPbeta for the C/EBP binding site at -53 on the CRP promoter, and that the transactivation domain of c-Rel is not necessary for this effect, which depends on protein: protein contacts with C/EBPbeta. PMID- 17335904 TI - Parkin polymorphisms and environmental exposure: decrease in age at onset of Parkinson's disease. AB - We tested the hypothesis that parkin polymorphisms (SNPs) and environmental exposure (EE) interact to reduce the age of onset of idiopathic Parkinson disease (PD). We prospectively and consecutively enrolled a total of 81 Italian PD patients. The diagnosis of PD was based on the UK Parkinson's Disease Society's brain bank criteria. Twenty-one patients with a positive family history for PD or tremor were excluded from the study. We collected information about medical history and EE. PARK1, PARK2 genes and PARK8 (exon 41) were screened. We detected one parkin mutation in a single patient and three parkin polymorphisms in a total of 25 patients; no alpha synuclein mutations, no common mutations of LRKK2 gene were found. The mutation-positive patient has been excluded from the study. The cohort of the remaining 59 patients has been divided into four subgroups, according to the presence/absence of parkin polymorphisms and the presence/absence of environmental factors-exposure. The age of onset of PD was significantly lower in patients with both SNPs and EE as compared to patients without (62.18+/-9.5 years versus 71.62+/-8 years, p=0.024; -13%). Patients with either SNPs or EE had an intermediate age of onset. The association of parkin polymorphisms and environmental exposure has a strong effect in lowering the age of onset of PD; the effect of environmental exposure or parkin polymorphisms alone seems to influence modestly the age of onset of PD. Individuals with environmental/occupational exposure should be screened for the presence of parkin SNPs. PMID- 17335905 TI - Cognitive function in a cohort of Danish steel workers. AB - OBJECTIVE: The aim of this study was to evaluate the level of possible cognitive impairment in a cohort of steel workers occupationally exposed to manganese and lead. MATERIAL: Ninety-two employees from an electro-steel works were examined in 1989 and 1995. Fifty-three were re-examined in 2003. Median age of the participants was 53 years, median duration of employment was 24 years, median blood manganese in 1989 and 1995 was 148 and 171 nmol/l, respectively, and median blood lead in 1989 was 0.79 micromol/l. Non-participants were comparable with participants, although they had a higher level of blood manganese in 1989 (186 nmol/l) and 1995 (186 nmol/l). Manganese level in the air was estimated below 1.9 mg/m3 in the 1970s. In the 1990s, manganese level in the air was below 0.28 mg/m3 in the majority of measurements. METHOD: Cognitive function was examined with the Cognitive Function Scanner, a computer-based neuropsychological test battery. From a published set of norms a subgroup (n=106) matched for gender, age and social status was extracted and used for comparison. RESULTS: Learning and memory, visuomotor and visuospatial function, concentration, attention, perception and vigilance were examined. Despite many statistically significant differences between the groups, it was not possible to interpret the results for the steel workers as being better or worse. In a visuomotor subtest, the pen-to point test, the steel workers were much less accurate than the comparison group. This could be the result of an impaired ability to make fast accurate movements. There were no associations between pen-to-point test results and duration of employment or blood levels of manganese and lead. CONCLUSION: Intellectual impairment could not be shown with the Cognitive Function Scanner in this cohort of low to moderate manganese and lead exposed steel workers. A slight subclinical impairment of the visuomotor function was possibly found. PMID- 17335906 TI - Computer automated movement detection for the analysis of behavior. AB - Currently, measuring ethanol behaviors in flies depends on expensive image analysis software or time intensive experimental observation. We have designed an automated system for the collection and analysis of locomotor behavior data, using the IEEE 1394 acquisition program dvgrab, the image toolkit ImageMagick and the programming language Perl. In the proposed method, flies are placed in a clear container and a computer-controlled camera takes pictures at regular intervals. Digital subtraction removes the background and non-moving flies, leaving white pixels where movement has occurred. These pixels are tallied, giving a value that corresponds to the number of animals that have moved between images. Perl scripts automate these processes, allowing compatibility with high throughput genetic screens. Four experiments demonstrate the utility of this method, the first showing heat-induced locomotor changes, the second showing tolerance to ethanol in a climbing assay, the third showing tolerance to ethanol by scoring the recovery of individual flies, and the fourth showing a mouse's preference for a novel object. Our lab will use this method to conduct a genetic screen for ethanol-induced hyperactivity and sedation, however, it could also be used to analyze locomotor behavior of any organism. PMID- 17335907 TI - Spatial-temporal analysis of fetal bio-magnetic signals. AB - Non-invasive technique such as magneto-encephalography (MEG), initially pioneered to study human brain signals, has found many other applications in medicine. SQUID(1) Array for Reproductive Assessment (SARA) is a unique non-invasive scanning-device developed at the University of Arkansas for Medical Sciences (UAMS) that can detect fetal brain and other signals. The fetal magneto encephalography (fMEG) signals often have many bio-magnetic signals mixed in. Examples include the movement of the fetus or muscle contraction of the mother. As a result, the recorded signals may show unexpected patterns, other than the target signal of interest. These "interventions" make it difficult for a physician to assess the exact fetal condition, including its response to various stimuli. We propose using intervention analysis and spatial-temporal auto regressive moving-average (STARMA) modeling to address the problem. STARMA is a statistical method that examines the relationship between the current observations as a linear combination of past observations as well as observations at neighboring sensors. Through intervention analysis, the change in a pattern due to "interfering" signals can be accounted for. When these interferences are "removed," the end product is a "template" time series, or a typical signal from the target of interest. In this research, a "universal" template is obtained. The template is then used to detect intervention in other datasets by the method of template matching. By this method, it is possible to detect if there is an intervention in any dataset. It will assist physicians in monitoring the actual signal generated by fetal brain and other organs of interest. PMID- 17335908 TI - High prevalence of serum autoantibodies against the amino terminal of alpha enolase in Hashimoto's encephalopathy. AB - Recently, we discovered autoantibodies against the amino (NH(2))-terminal of alpha-enolase (NAE) in patients with Hashimoto's encephalopathy (HE) (83.3%; 5/6) [Fujii, A., Yoneda, M., Ito, T., Yamamura, O., Satomi, S., Higa, H., Kimura, M., Suzuki, M., Yamashita, M., Yuasa, T., Suzuki, H., Kuriyama, M., 2005. Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker of Hashimoto's encephalopathy. J. Neuroimmunol. 162, 130-136]. We further investigated the anti-NAE autoantibodies in 25 patients who fit the diagnostic criteria for HE, based on the presence of anti-thyroid antibodies and responsiveness to immunotherapy. In this study, we demonstrated a high prevalence (68%, 17 of 25) and high specificity of anti-NAE autoantibodies in patients with HE, and clarified the clinical features of HE. This result demonstrated that anti NAE autoantibodies, in addition to anti-thyroid autoantibodies, are emphasized as useful serological diagnostic markers of HE. PMID- 17335909 TI - Effect of sera from AChR-antibody negative myasthenia gravis patients on AChR and MuSK in cell cultures. AB - A proportion of patients with myasthenia gravis (MG) do not have antibodies to the acetylcholine receptor (AChR). Some of these patients have antibodies to muscle specific kinase (MuSK), whereas others have neither antibody (seronegative MG, SNMG). Both MuSK antibody positive MG (MuSK-MG) and SNMG are antibody mediated diseases but how they cause neuromuscular junction failure is not clear. One possibility is that they reduce the clustering and expression of AChRs. We looked at the effects of MuSK-MG and SNMG sera/IgG on surface AChR distribution and expression, and AChR subunit and MuSK mRNA by quantitative RT-PCR, in TE671 and C2C12 myotubes. In TE671 cells MuSK-MG sera reduced AChR expression by about 20%, but had no effect on AChR subunit or MuSK mRNA expression. In C2C12 myotubes, MuSK-MG sera caused a reduction in the number of agrin-induced clusters, but the clusters became larger and there was no significant effect on total surface AChR numbers or AChR subunit or MuSK mRNA. By contrast, SNMG sera not only reduced AChR numbers by about 20% in TE671 cells, but modestly upregulated AChR gamma subunit expression in TE671 cells and both AChR gamma subunit and MuSK expression in C2C12 myotubes. Thus, although these results have, disappointingly, demonstrated little effect of MuSK antibodies on AChR expression, they do imply that SNMG antibodies act on AChR-associated pathways. PMID- 17335910 TI - 500Hz logon versus click ABR maturation. AB - OBJECTIVES: To provide age-equivalent norms for a 500Hz logon evoked ABR obtained in a group of children ranging 40 weeks-4 years old and compare these 500Hz tonal norms to age-equivalent norms for click-evoked ABR. METHODS: Seventy-seven infants and children ranging from conceptional age of 40 weeks (term babies) to 4 years were tested with both click and tonal ABR without any risk factors for hearing loss. RESULTS: Data analyses were consisted of 6 age groups. Mean wave V latencies were compared with the adult norms. Latencies were decreased by age in both click and tonal ABR recordings. CONCLUSION: Five hundred Hertz of tonal ABR wave V latency did not mature until to 2-4 years old but, click ABR wave V latency reached maturity at the same age range. PMID- 17335911 TI - Spontaneous extradural hematoma as a presentation of sinusitis: case report and literature review. AB - Spontaneous extradural hematoma is rarely mentioned in literature as intracranial complications of sinusitis. The authors presented a girl with spontaneous extradural hematoma secondary to pansinusitis and reviewed the literature. In a child with spontaneous extradural hematoma without a history of head trauma, sinusitis should be excluded. PMID- 17335912 TI - A community based questionnaire study on the association between symptoms suggestive of otitis media with effusion, rhinitis and asthma in primary school children. AB - OBJECTIVES: To evaluate the association between symptoms suggestive of otitis media with effusion (OME), rhinitis and asthma in an unselected population of primary school children and investigate whether our previous observation of such an association in a secondary care setting was valid in the community. METHODOLOGY: A specifically designed questionnaire was administered to 332 new entrant primary school children across 11 state and independent primary schools in the East Berkshire district between March and June 1996. It had six sections, to ascertain symptoms suggestive of OME, rhinitis, asthma, other atopic features, treatment for any of these, and a possible family history of atopy. Within the first three sections, each question was scored and weighted depending on the importance of each in establishing the possible diagnoses, with three scoring bands: '0' indicating the absence; '1-5' the possibility and '> or =6' a strong likelihood that the above conditions were present. The outcome measures were the number of children with or without symptoms suggestive of OME, rhinitis, asthma, and the correlation of these symptom scores with each other and OME with eczema, other atopic manifestations, family history of atopy and educational system. RESULTS: Thirty two point eight percent, thirty six point six percent and twenty four percent had symptoms suggestive of OME, rhinitis and asthma, respectively with scores of either 1-5 or > or =6. There was a highly significant correlation between otological (OME) and nasal scores (p=0.00000), particularly obstructive nasal symptoms (p=0.00000) and > or =6 upper respiratory tract infections/year (p=0.00000); otological and chest scores suggestive of asthma (p=0.00001), and a family history of asthma (p=0.00178). No association was found between scores for OME and eczema, urticaria, food or drug allergies. No differences were noted between the sexes or educational systems. CONCLUSION: The highly significant association between the symptom scores suggestive of OME and rhinitis in this unselected population, indicates the importance of enquiring about nasal symptoms in children with chronic OME, as appropriate treatment of rhinitis may improve the child's quality of life, reduce health care utilisation and possibly reduce the need for OME surgery. PMID- 17335913 TI - Biophysical characterization of vaccinia virus thymidine kinase substrate utilization. AB - To provide information for the development of new antiviral compounds that inhibit orthopoxviruses, further characterization of the kinetics and thermodynamics that underlie substrate utilization reactions of vaccinia virus thymidine kinase (VVTK) has been undertaken. The kinetics of 2'deoxythymidine phosphorylation by VVTK and the thermodynamics of complex formation between VVTK and the substrate 2' deoxythymidine were determined using spectroscopic and calorimetric techniques. These studies demonstrated that kinetic parameters for 2' deoxythymidine phosphorylation by VVTK were 25 microM and 0.2s(-1) for K(m) and k(cat), respectively. The enthalpy change, Delta H, for the enzyme catalyzed reaction is -18.1 kcal/mol. Thermodynamic studies for the formation of the enzyme substrate complex demonstrated a binding affinity (K(a)) of 4 x 10(4)M(-1), an enthalpy change for binding (Delta H) of -17.4 kcal/mol, and a reaction stoichiometry of two molecules of substrate binding to each enzyme tetramer. Kinetic and thermodynamic data were in agreement (K(a) approximately 1/K(m)) and showed similarities to literature values reported for herpes simplex virus thymidine kinase (HSV-TK) and human thymidine kinase 1 (hTK1) with respect to k(cat) but not with respect to K(m). The K(m) value found for VVTK in this study is nearly two orders of magnitude larger than the values reported for the hTK1 and the HSV TK enzymes. PMID- 17335914 TI - Long-term depression: multiple forms and implications for brain function. AB - Long-term potentiation (LTP) and long-term depression (LTD) remain widely accepted vertebrate models for the cellular and molecular mechanisms that underlie synaptic changes during learning and memory. Although LTD is a phenomenon that occurs in many regions of the CNS, it is clear that the mechanisms recruited in its induction and expression can vary, depending on many factors, including brain region and developmental time point. LTD in the hippocampus and cerebellum is probably the best characterized, although there are also other brain areas where mechanisms of LTD are well understood, and where it is thought to have a functional role. PMID- 17335915 TI - Role of gastrin-releasing peptide and neuromedin B in anxiety and fear-related behavior. AB - Bombesin (BB)-like peptides have been implicated in the mediation and/or modulation of the stress response. However, the impact of manipulating this peptidergic system has only been assessed in a limited number of anxiety and fear paradigms. Given that different behavioral paradigms reflect different aspects of anxiety, the objective of the present investigation was to assess the effects of two mammalian BB-related peptides, namely gastrin-releasing peptide (GRP) and neuromedin B (NMB), in paradigms thought to reflect fear and anxiety-related behaviors. To this end, the effects of central (3rd ventricular; i.c.v.) administration of GRP (0.30 nmol), GRP receptor (BB(2)) antagonist, [Leu(13) (CH(2)NH)Leu(14)]-BN (1.26 nmol), NMB-30 (0.29 nmol), NMB (BB(1)) receptor antagonist, BIM 23127 (1.70 nmol) and a mixed BB(1)/BB(2) receptor antagonist, PD 176252 (0.621 nmol) were assessed in the elevated plus maze (EPM) and in a fear potentiated startle paradigm (a model thought to reflect conditioned fear). The BB(1) receptor antagonist and the mixed BB(1)/BB(2) receptor antagonist elicited anxiolytic effects in the EPM, whereas, the BB(2) receptor antagonist was without effect. In the fear potentiated startle paradigm, pretreatment with either the BB(1) receptor antagonist or the BB(2) receptor agonist attenuated the fear potentiated startle response, without affecting basal startle amplitude. These data suggest that NMB and GRP do affect the stress response. However, whereas NMB manipulations affected both anxiety and fear responses, GRP alterations selectively affected fear-related responses. PMID- 17335916 TI - Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress. AB - The roles of beta-NER (beta-noradrenergic receptor), GR (glucocorticoid) and mineral corticoid receptors (MR) in the consolidation of anxiogenic effects of predator stress were studied. One minute after predator stress, different groups of rats were injected (ip) with vehicle, propranolol (beta-NER blocker, 5 and 10 mg/kg), mifepristone (RU486, GR blocker, 20 mg/kg), spironolactone (MR blocker, 50 mg/kg), propranolol (5 mg/kg) plus RU486 (20 mg/kg) or the anxiolytic, chloradiazepoxide (CPZ, 10 mg/kg). One week later, rodent anxiety was assessed in elevated plus maze, hole board, light/dark box, social interaction and acoustic startle. Considering all tests except startle, propranolol dose dependently blocked consolidation of lasting anxiogenic effects of predator stress in all tests. GR receptor block alone was ineffective. However, GR block in combination with an ineffective dose of propranolol did blocked consolidation of predator stress effects in all tests, suggesting a synergism between beta-NER and GR. Surprisingly, MR block prevented consolidation of anxiogenic effects in all tests except the light/dark box. CPZ post stress was ineffective against the anxiogenic impact of predator stress. Study of startle was complicated by the fact that anxiogenic effects of stress on startle amplitude manifested as both an increase and a decrease in startle amplitude. Suppression of startle occurred in stressed plus vehicle injected groups handled three times prior to predator stress. In contrast, stressed plus vehicle rats handled five times prior to predator stress showed increases in startle, as did all predator stressed only groups. Mechanisms of consolidation of the different startle responses appear to differ. CPZ post stress blocked startle suppression but not enhancement of startle. Propranolol post stress had no effect on either suppression or enhancement of startle. GR block alone post stress prevented suppression of startle, but not enhancement. In contrast blocking GR and beta-NER together prevented startle enhancement. MR block also prevented startle enhancement. Effects of MR block on startle suppression were not tested. Delay of habituation to startle was found in all stressed rats. Consolidation of delay of habituation was blocked or attenuated by post stress MR block, GR plus beta-NER block and CPZ but not by post stress GR or beta-NER block alone. Taken together, present findings suggest consolidation of lasting anxiogenic effects of predator stress may share some of the same neurochemical mechanisms implicated in some forms of fear memory consolidation. Implications of these findings for the study of stress-induced changes in affect including posttraumatic stress disorder (PTSD) are discussed. PMID- 17335917 TI - Ibotenic acid lesions to ventrolateral thalamic nuclei disrupts trace and delay eyeblink conditioning in rabbits. AB - Intact cerebellar structures (i.e., deep nuclei and perhaps cortex) are essential for acquisition of both simple delay and trace eyeblink (EB) conditioning. However, successful trace conditioning also requires intact cortico-limbic structures (i.e., hippocampus, medial thalamus, and medial prefrontal cortex, mPFC). A direct connection between the cerebellum and ventrolateral thalamic nuclei (VLTN) has been demonstrated in several species. Since VLTN projects to both premotor and prefrontal cortex, it may be an essential link in a cerebellar thalamic-prefrontal circuit that provides the CNS substrate for acquisition of the trace EB CR. The current studies thus assessed the role of the VLTN on trace EB conditioning in New Zealand albino rabbits. We first verified afferent connections to the mPFC (Brodmann's area 32) from the VLTN, by injecting the retrograde tracer Flourogold(c) into area 32. Strong labeling in VLTN from terminal projections to mPFC were found. We next assessed the role of VLTN in trace eyeblink conditioning in animals that received either sham or ibotenic acid VLTN lesions. EB conditioning began with 10 consecutive daily sessions of trace conditioning, followed immediately by 4 days of extinction, and then 4 days of delay conditioning. VLTN lesions significantly impaired acquisition of both trace and delay conditioning, and impaired extinction. These findings, thus confirm the importance of the VLTN in a postulated cerebellar-thalamic-prefrontal circuit that underlies successful trace, as well as delay EB conditioning. PMID- 17335918 TI - Cell cycle regulation in Trypanosoma brucei. AB - Cell division is regulated by intricate and interconnected signal transduction pathways that precisely coordinate, in time and space, the complex series of events involved in replicating and segregating the component parts of the cell. In Trypanosoma brucei, considerable progress has been made over recent years in identifying molecular regulators of the cell cycle and elucidating their functions, although many regulators undoubtedly remain to be identified, and there is still a long way to go with respect to determining signal transduction pathways. However, it is clear that cell cycle regulation in T. brucei is unusual in many respects. Analyses of trypanosome orthologues of conserved eukaryotic cell cycle regulators have demonstrated divergence of their function in the parasite, and a number of other key regulators are missing from T. brucei. Cell cycle regulation differs in different parasite life cycle stages, and T. brucei appears to use different checkpoint control strategies compared to model eukaryotes. It is therefore probable that T. brucei has evolved novel pathways to control its cell cycle. PMID- 17335919 TI - The role of metacaspase 1 in Plasmodium berghei development and apoptosis. AB - The malaria parasite encodes a wide range of proteases necessary to facilitate its many developmental transitions in vertebrate and insect hosts. Amongst these is a predicted cysteine protease structurally related to caspases, named Plasmodium metacaspase 1 (PxMC1). We have generated Plasmodium berghei parasites in which the PbMC1coding sequence is removed and replaced with a green fluorescent reporter gene to investigate the expression of PbMC1, its contribution to parasite development, and its involvement in previously reported apoptosis-like cell death of P. berghei ookinetes. Our results show that the pbmc1 gene is expressed in female gametocytes and all downstream mosquito stages including sporozoites, but not in asexual blood stages. We failed to detect an apparent loss-of-function phenotype, suggesting that PbMC1 constitutes a functionally redundant gene. We discuss these findings in the context of two other putative Plasmodium metacaspases that we describe here. PMID- 17335920 TI - Up-regulation of galanin and corticotropin-releasing hormone mRNAs in the key hypothalamic and amygdaloid nuclei in a mouse model of visceral pain. AB - Cyclophosphamide (CP)-induced cystitis is often used as an animal model of visceral pain. Various neuropeptides in the hypothalamic and amygdaloid nuclei are implicated in pain-induced responses. However, little information is available regarding the regulation of the neuropeptides in response to visceral pain. In the present study, we examined the effects of CP-induced cystitis on the levels of mRNAs encoding galanin, corticotropin-releasing hormone (CRH), substance P, and enkephalins in the hypothalamic and limbic nuclei using in situ hybridization histochemistry in mouse. Galanin mRNA levels in CP-treated group increased significantly in the arcuate nucleus and the paraventricular nucleus (PVN) but not in the medial preoptic area after the intraperitoneal administration of CP (200 mg/kg body weight) in comparison to those in saline treated group. CRH mRNA levels in CP-treated group also increased significantly in the central amygdala as well as the PVN after the CP administration. In contrast, CP-induced cystitis failed to upregulate the preprotachykinin-A and preproenkephalin genes which encode substance P and enkephalins, respectively in the hypothalamic and limbic nuclei at any of the time points examined. These results suggest that visceral nociception may upregulate both galanin and CRH gene expression in the hypothalamic and limbic nuclei. PMID- 17335921 TI - Protease-activated receptor-1 (PAR1) and PAR2 but not PAR4 mediate relaxations in lower esophageal sphincter. AB - Protease-activated receptor-1 (PAR1), PAR2 and PAR4 activation can alter the gastrointestinal motility. To investigate effects mediated by PARs in the lower esophageal sphincter, we measured contraction or relaxation of transverse strips from the guinea-pig lower esophageal sphincter caused by PAR1 (TFLLR-NH2 and SFLLRN-NH2), PAR2 (SLIGKV-NH2 and SLIGRL-NH2) and PAR4 peptide agonists (GYPGKF NH2, GYPGQV-NH2 and AYPGKF-NH2) as well as PAR protease activators (thrombin and trypsin). In resting lower esophageal sphincter strips, TFLLR-NH2 and SFLLRN-NH2 caused moderate concentration-dependent relaxation whereas thrombin did not cause any relaxation or contraction. Furthermore, in carbachol-contracted strips, TFLLR NH2 and SFLLRN-NH2 caused marked whereas thrombin caused mild concentration dependent relaxation. These indicate the existence of PAR1 mediating relaxation. Similarly, in resting lower esophageal sphincter strips, trypsin caused moderate concentration-dependent relaxation whereas SLIGRL-NH2 and SLIGKV-NH2 did not cause any relaxation or contraction. In addition, in carbachol-contracted strips, trypsin caused marked whereas SLIGRL-NH2 and SLIGKV-NH2 caused mild concentration dependent relaxation. These indicate the existence of PAR2 mediating relaxation. The relaxant response of thrombin, TFLLR-NH2, trypsin and SLIGKV-NH2 was insensitive to atropine or tetrodotoxin, suggesting a direct effect. The relaxant response of trypsin was not affected by apamin, charybdotoxin, indomethacin and capsaicin but was attenuated by NG-nitro-L-arginine methyl ester, indicating involvement of NO. FSLLR-NH2, a PAR1 control peptide, and VKGILS-NH2, a PAR2 control peptide, as well as all three PAR4 peptide agonists, GYPGKF-NH2, GYPGQV NH2 and AYPGKF-NH2, did not cause any relaxation or contraction. Taken together, these results demonstrate that PAR1 and PAR2 but not PAR4 mediate relaxations in the guinea-pig lower esophageal sphincter. PMID- 17335922 TI - Acute coronary syndrome due to hinge movement of a bare-metal stent. AB - Recently, attention has been given to stent fracture (SF) as a risk factor of in stent restenosis. SF is sometimes revealed at the site of hinge movement (HM). HM synchronized to heart beats might cause chronic mechanical stress of the vessel wall, resulting in chronic inflammation and mobilization of inflammatory cells, and this might lead to formation of atheromatous plaque. A 59-year-old man in whom a bare metal stent (BMS) had been deployed to the right coronary artery 9 years ago visited our clinic due to acute coronary syndrome (ACS). Emergency coronary angiography revealed HM at the site of the BMS where thrombotic occlusion was revealed. ACS might be caused by chronic mechanical stress due to HM of the BMS. PMID- 17335923 TI - Nestin, a maker for multilineage potential of cells from human primary and restenotic coronary artery plaques. AB - Nestin is a type of intermediate filament abundantly expressed in neuroepithelial stem cells or mesenchymal stem cells. We assessed directional coronary atherectomy specimens from primary and restenotic lesions for expression of nestin. Immunohistochemistry showed predominant expression of nestin in stellate smooth muscle cells (SMCs). Given that nestin has been proposed to be a marker for putative stem cells, our results suggest that human coronary plaques contain cells that have the potential for multiple lineages. Although the role of nestin remains unclear, nestin-positive stellate SMCs are more frequently seen in patients with unstable angina. PMID- 17335924 TI - Coronary spasm after injection of ondansetron: case report and review of the literature. PMID- 17335925 TI - Characterization of neuron-specific huntingtin aggregates in human huntingtin knock-in mice. AB - Huntington's disease (HD) is caused by a mutation causing expanded polyglutamine tracts in the N-terminal fragment of huntingtin. A pathological hallmark of HD is the formation of aggregates in the striatal neurons. Here we report that ageing human huntingtin knock-in mice expressing mutant human huntingtin contained neuronal huntingtin aggregates, as revealed by immunohistochemical analysis. In heterozygous knock-in mice with 77 CAG repeats, aggregates of N-terminal fragments of huntingtin were specifically formed in nuclei and neuropils in the striatal projection neurons, and in neuropils in their projection regions. This aggregate formation progressed depending on age, became interacted with proteolytic or chaperone proteins, and occurred most prominently in the nucleus accumbens. These mutant mice demonstrated abnormal aggressive behavior. In homozygous knock-in mice, heavy deposits of intranuclear and neuropil aggregates were detected, which extended to other regions; and characteristic large perikaryal aggregates were also found in the affected neurons. However, cell death was not observed among the striatal and affected neurons of these mutant mice. Our results indicate that the polyglutamine aggregates do not necessarily correlate with neuronal death. These human huntingtin knock-in mice should be useful to provide an effective therapeutic approach against HD. PMID- 17335926 TI - Characterization of a new fibroblast cell line from a tail fin of red sea bream, Pagrus major, and phylogenetic relationships of a recent RSIV isolate in Japan. AB - Red sea bream iridovirus (RSIV) is a causative agent of red sea bream iridoviral disease (RSIVD) in marine fish species in Japan. Fibroblast cells were developed from a tail fin of red sea bream, Pagrus major, and then underwent single cell cloning. The successful cloned cells were named CRF-1 cells. Most CRF-1 cells had a normal diploid karyotype with 2n=48 by chromosomal analysis. RSIV-infected CRF 1 cells showed typical morphological changes that were associated with apoptosis by EGFP-annexin V staining. The serial viral passages were successful in CRF-1 cells but failed in BF-2 cells as judged by MTT assay. The expression of three genes obviously decreased in BF-2 cells compared with CRF-1 cells and finally was below detectable level. Because the expression of 591R gene showed the fastest decrease among three transcripts, the suppression of IE transcript may be responsible for the restricted replication in BF-2 cells. MCP and ATPase phylogenetic trees showed that RSIV strain U-1 belongs to a distinct group from RSIV strain ehime-1. Therefore, possibly recent epizootics of RSIVD in Japan do not originate directly from RSIV strain ehime-1. Taken together, this study confirmed that RSIV strain U-1 is more closely related to Korean RSIV isolates. PMID- 17335928 TI - AOPP and its relations with selected markers of oxidative/antioxidative system in type 2 diabetes mellitus. AB - BACKGROUND: The aim of this study was to evaluate the selected components of the oxidative/antioxidative system in T2DM; estimation of relationships between them; search for the more expressive one and examine their alterations in angiopathy and obesity. METHODS: In 94 diabetic patients and 36 healthy people, plasma levels of TRAP, as a marker of antioxidative defence, as well as concentrations of CO, SH, and NH(2) groups and AOPP, as markers of oxidative protein damage (OPD) were determined. RESULTS: Patients had significantly lower levels of TRAP and SH groups, as well as higher NH(2), CO and AOPP in comparison to control. Significant correlation was observed between TRAP and SH groups and AOPP as well as between AOPP and SH and CO groups. Concentration of AOPP was significantly higher in the macroangiopathy and obese subgroups. CONCLUSIONS: Our results support the idea that diabetes mellitus is a complex metabolic disorder with oxidant/antioxidant defence disturbances. Among the studied parameters AOPP showed the most expressive raise in plasma of diabetic patients and significant differences between their subgroups with vascular complications and overweight. We can conclude that AOPP seems to be considered as a useful marker to estimate the degree of OPD in diabetic patients. PMID- 17335927 TI - Optimum conditions for efficient phagocytosis of rifampicin-loaded PLGA microspheres by alveolar macrophages. AB - We examined the phagocytic activities of alveolar macrophages (NR8383 cells) toward poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with the anti-tuberculosis agent rifampicin (RFP), the sizes of which were between 1 microm and 10 microm. We found that 1) the phagocytosis was dependent greatly on the particle size and the number of particles added; 2) macrophages phagocytosed considerably the PLGA microspheres loaded with RFP, the diameter of which was between 1 microm and 6 microm, but took up few 10-microm particles; 3) the population of the macrophages that phagocytosed 1-microm or 3-microm particles was larger than that of those phagocytosed 6- or 10-microm particles; 4) a considerable population of macrophages were not able to phagocytose even the 1- and 3-microm particles; 5) the most efficient deliveries of RFP into each macrophage cell and a large population of macrophages were achieved by the phagocytosis of 3-microm particles; and 6) phagocytosis did not affect macrophage viability in 4 h after the start of phagocytosis. PMID- 17335929 TI - Morbidity and mortality in paid Austrian plasma donors infected with hepatitis C at plasma donation in the 1970s. AB - BACKGROUND/AIMS: Between 1964 and 1987 several epidemic outbreaks of hepatitis C virus infection linked to plasma donation occurred at plasmapheresis centres in Austria. Data collected by a Foundation to help the victims enabled us to study the natural history of chronic hepatitis C in this cohort. METHODS: Medical records and charts of donors accepted by the Foundation were analyzed. RESULTS: Four hundred and eighty-five subjects (439 males; mean age at infection: 22 years) were included. Mean follow-up was 31 years. Thirty-four percent of plasma donors had advanced liver disease; alcohol abuse and diabetes were related to progression. Twenty-one patients developed hepatocellular carcinoma; 36 underwent liver transplantation. Six donors cleared the virus spontaneously. Forty died, with death directly related to liver disease in 25 donors. Overall and transplant free 35-year cumulative survival rates were 84% and 74%, respectively. Three hundred and nineteen patients received and 291 completed antiviral treatment. All 56 who achieved a sustained virologic response are alive and well; 14 non responders died and nine underwent liver transplantation. CONCLUSIONS: Thirty-one years after virus infection, advanced liver disease has developed in a third of patients, with an overall mortality of 7%. These data underline the progressive nature of chronic hepatitis C infection and the need to identify and treat infected subjects. PMID- 17335930 TI - Differences and similarities in early atherosclerosis between patients with non alcoholic steatohepatitis and chronic hepatitis B and C. AB - BACKGROUND/AIMS: To compare carotid intima-media thickness (IMT) - an index of early atherosclerosis - among patients with non-alcoholic steatohepatitis (NASH), patients with chronic hepatitis B (HBV) or C (HCV) and control subjects. METHODS: We studied 60 consecutive patients with biopsy-proven NASH, 60 patients with HCV, 35 patients with HBV, and 60 healthy controls who were comparable for age and sex. Common carotid IMT was measured with ultrasonography in all participants by a single operator blinded to subjects' characteristics. RESULTS: Carotid IMT measurements were markedly different among the groups; the lowest values were in controls, intermediate in patients with HBV or HCV, and highest in those with NASH (0.84+/-0.1 vs. 0.97+/-0.1 vs. 1.09+/-0.2 vs. 1.23+/-0.2mm, respectively; p<0.001). The marked differences in carotid IMT that were observed among the groups were little affected by adjustment for age, sex, body mass index, smoking, LDL cholesterol, insulin resistance (by homeostasis model assessment) and components of the Adult Treatment Panel III-defined metabolic syndrome. Concordantly, in logistic regression analysis, NASH, HBV and HCV predicted carotid IMT independent of potential confounders. CONCLUSIONS: These data suggest that NASH, HCV and HBV are strongly associated with early atherosclerosis independent of classical risk factors, insulin resistance and metabolic syndrome components. PMID- 17335931 TI - Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4 cirrhotic rats. AB - BACKGROUND/AIMS: Sinusoidal endothelial dysfunction with decreased nitric oxide (NO) production contributes to increased hepatic resistance in cirrhosis. Statins improve endothelial dysfunction in peripheral vasculature. This study was designed to characterize the hemodynamic and molecular effects of statins in cirrhotic rats. METHODS: Systemic and splanchnic hemodynamics were evaluated in CCl(4) ascitic cirrhotic rats treated with placebo or simvastatin (25 mg/kg/day, for 3 days), at baseline and after volume expansion. Vascular responses of liver vasculature were evaluated after isolation and perfusion of the liver. RESULTS: There were no differences in baseline hemodynamics in rats treated with simvastatin or placebo. However, in rats treated with simvastatin the increase in portal pressure induced by volume expansion was significantly attenuated. In isolated and perfused cirrhotic livers simvastatin pre-treatment significantly attenuated the pressure response to methoxamine, and significantly improved paradoxical vasoconstriction induced by acetylcholine. These effects were not observed in the presence of a nitric oxide synthase inhibitor. Simvastatin increased eNOS expression, Akt-dependent eNOS phosphorylation and cGMP liver content. CONCLUSIONS: The administration of simvastatin might constitute a new way to selectively increase NO availability in the cirrhotic liver circulation and, therefore improve the vascular disturbances that contribute to portal hypertension. PMID- 17335932 TI - Sustained public preferences on hospital performance across Canadian provinces. AB - OBJECTIVES: To compare the Canadian public's view of various components of hospital performance at two points in time, and to investigate differences across provinces. METHODS: Random telephone interviews were conducted across Canada in 2001 and again in 2004. Respondents were asked to rate the importance of 10 aspects of hospital performance including coordination, skills of providers, the use of technology, medical errors, and waiting times. Aggregate importance scores were estimated in 2001 and 2004 and compared using t-tests. Provincial comparisons were investigated using analysis of covariance (ANCOVA) with a Bonferroni correction of 0.005 (0.05/10). The covariates were sex, age, marital status, education, working status, and income. RESULTS: Public preferences were similar across provinces and consistent over the two periods; however, respondents from Quebec showed a pattern somewhat different in each year and over time. Overall, the importance scores in Quebec tended to be lower than those from the other provinces. Respondents from all provinces except Quebec ascribed the greatest value to 'skill of medical staff' in 2001 and 2004. Those from Quebec, however, gave the highest rating to 'skill of medical staff' in 2001 and 'medical errors' in 2004; the latter climbed from the 8th to the 1st place over time. All respondents gave 'waiting time for a non-emergency surgical procedure' the lowest score in both years, although its importance score increased a significant 18% between 2001 and 2004 excluding the responses from Quebec. Significant covariates were sex, marital status, and education. CONCLUSIONS: Public preferences can help inform the work of health care policy and decision makers, particularly that related to resource allocation decisions. PMID- 17335933 TI - A national hypertension treatment program in Germany and its estimated impact on costs, life expectancy, and cost-effectiveness. AB - Almost 15 million Germans may suffer from untreated hypertension. The purpose of this paper is to estimate the cost-effectiveness of a national hypertension treatment program compared to no program. A Markov decision model from the perspective of the statutory health insurance (SHI) was built. All data were taken from secondary sources. The target population consists of hypertensive male and female patients at high or low risk for cardiovascular events at different age groups (40-49, 50-59, and 60-69 years). The analysis shows fairly moderate cost-effectiveness ratios even for low-risk groups (less than 12,000 euros per life year gained). In women at high risk antihypertensive treatment even leads to savings. This suggests that a national hypertension treatment program provides good value for money. Given the considerable costs of the program itself, any savings from avoiding long-term consequences of hypertension are likely to be offset, however. PMID- 17335934 TI - Multi-time-scale heat transfer modeling of turbid tissues exposed to short-pulsed irradiations. AB - A combined hyperbolic radiation and conduction heat transfer model is developed to simulate multi-time-scale heat transfer in turbid tissues exposed to short pulsed irradiations. An initial temperature response of a tissue to an ultrashort pulse irradiation is analyzed by the volume-average method in combination with the transient discrete ordinates method for modeling the ultrafast radiation heat transfer. This response is found to reach pseudo steady state within 1 ns for the considered tissues. The single pulse result is then utilized to obtain the temperature response to pulse train irradiation at the microsecond/millisecond time scales. After that, the temperature field is predicted by the hyperbolic heat conduction model which is solved by the MacCormack's scheme with error terms correction. Finally, the hyperbolic conduction is compared with the traditional parabolic heat diffusion model. It is found that the maximum local temperatures are larger in the hyperbolic prediction than the parabolic prediction. In the modeled dermis tissue, a 7% non-dimensional temperature increase is found. After about 10 thermal relaxation times, thermal waves fade away and the predictions between the hyperbolic and parabolic models are consistent. PMID- 17335935 TI - EGFR mutation status in pleural fluid predicts tumor responsiveness and resistance to gefitinib. AB - It has been reported that the threonine-to-methionine substitution at amino acid position 790 (T790M) of the epidermal growth factor receptor (EGFR) gene is correlated with acquired resistance to gefitinib. We previously reported that there was some population that harbored the EGFR T790M mutation as a minor clone of tumor cells prior to drug treatment, may be causing resistance to gefitinib during treatment. This fact also suggests that the detection of the EGFR T790M mutation prior to treatment may predict the development of resistance. We also showed that pleural fluid is a useful specimen for detection of EGFR mutation using sensitive assays. In this study, we reported a female patient who was treated with gefitinib because an EGFR L858R mutation was found in her pleural fluid. Our patient showed partial response to gefitinib, but she had progressive disease only 4 months after the start of treatment. Furthermore, the EGFR T790M mutation was detected in the pleural fluid before gefitinib treatment by the mutant-enriched PCR assay. Our findings confirmed that the EGFR T790M mutation was occasionally present as a minor population in tumor cells before treatment and caused resistance after gefitinib administration. The detection of a small fraction of T790M-positive alleles may be useful to predict the clinical course of the gefitinib-treated non-small-cell lung cancer patients. PMID- 17335936 TI - Maximizing the efficiency of conservation. PMID- 17335938 TI - Influence of gender, age and motives underlying food choice on perceived healthiness and willingness to try functional foods. AB - The aims of the present study were to study the effect of different carriers and enrichments on the perceived healthiness and willingness to try functional foods; and to evaluate the effect of age, gender and motives underlying food choice. Participants had to evaluate different functional food concepts and had to answer a food choice questionnaire. Results showed that carrier products had the largest effect on consumers' perception of healthiness and willingness to try of the evaluated functional foods concepts. The highest positive relative utilities were achieved when the enrichment was a functional ingredient inherent in the product. Furthermore, gender, age and motives underlying food choice affected the preference patterns for the evaluated functional foods concepts, but it depended on the carrier and enrichment considered, suggesting that functional foods might not be accepted by all the consumers and that they could be tailored for certain groups. PMID- 17335939 TI - 3D-QSAR and molecular docking study on bisarylmaleimide series as glycogen synthase kinase 3, cyclin dependent kinase 2 and cyclin dependent kinase 4 inhibitors: an insight into the criteria for selectivity. AB - Selective glycogen synthase kinase 3 (GSK3) inhibition over cyclin dependent kinases such as cyclin dependent kinase 2 (CDK2) and cyclin dependent kinase 4 (CDK4) is an important requirement for improved therapeutic profile of GSK3 inhibitors. The concepts of selectivity and additivity fields have been employed in developing selective CoMFA models for these related kinases. Initially, sets of three individual CoMFA models were developed, using 36 compounds of bisarylmaleimide series to correlate with the GSK3, CDK2 and CDK4 inhibitory potencies. These models showed a satisfactory statistical significance: CoMFA GSK3 (r(2)(con), r(2)(cv): 0.931, 0.519), CoMFA-CDK2 (0.937, 0.563), and CoMFA CDK4 (0.892, 0.725). Three different selective CoMFA models were then developed using differences in pIC(50) values. These three models showed a superior statistical significance: (i) CoMFA-Selective1 (r(2)(con), r(2)(cv): 0.969, 0.768), (ii) CoMFA-Selective 2 (0.974, 0.835) and (iii) CoMFA-Selective3 (0.963, 0.776). The selective models were found to outperform the individual models in terms of the quality of correlation and were found to be more informative in pinpointing the structural basis for the observed quantitative differences of kinase inhibition. An in-depth comparative investigation was carried out between the individual and selective models to gain an insight into the selectivity criterion. To further validate this approach, a set of new compounds were designed which show selectivity and were docked into the active site of GSK3, using FlexX based incremental construction algorithm. PMID- 17335940 TI - Synthesis of novel triazole derivatives as inhibitors of cytochrome P450 14alpha demethylase (CYP51). AB - A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4 substitutedphenyl)-piperazin-1-yl]-propan-2-ols have been designed and synthesized on the basis of the structure-activity relationships and antimycotic mechanism of azole antifungal agents. Their structures were confirmed by elemental analysis, IR, MS and (1)H NMR. Results of preliminary antifungal tests against eight human pathogenic fungi (Candida albicans, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans, Aspergillus fumigatus, Trichophyton rubrum, Fonsecaea compacta, and Microsporum gypseum) in vitro showed that all title compounds exhibited activity against fungi tested to some extent. Among the compounds tested, all compounds showed higher activity against C. albicans than fluconazole in vitro. Compounds 3, 6-8, 28, 29, and 32 exhibited the same activities against C. albicans as voriconazole (with the MIC value of 0.0152microg/mL). Compounds 3, 6, and 7 showed higher activity against C. parapsilosis than all five positive controls. PMID- 17335941 TI - [Hydatid disease of bone: a report of 2 cases]. AB - INTRODUCTION: The hydatid cyst of Echinococcus granulosus tends to develop in liver. The primary bone hydatidosis is rare. EXEGISIS: The authors report 2 cases of primary hydatidosis of bone in a 57 year old men and 60 year old diabetic women. The symptoms and signs were not specific. The ultrasound investigation: standard radiography and computed tomographic scan, was suggestive of the lesion. The chest radiograph and the abdominal ultrasound were normal. Serological tests for hydatid disease were positive. The two patients have surgical excision and medical treatment: Albendazole administrated for 6 months. Histologic evidence confirmed the diagnosis. The outcome was good for both patients without recurrence after 2 years. CONCLUSION: Through these 2 cases and a review of the literature, the authors analyse the epidemiological and clinical aspects of bone hydatidosis and discuss the therapeutic procedures. PMID- 17335942 TI - [Pericarditis: a giant cell arteritis manifestation]. AB - INTRODUCTION: Temporal arteritis is a vasculitis in which inflammatory manifestations mainly involve the external carotid artery area but not exclusively. Through a clinical observation and a review of the literature, we suggest that inflammatory pericarditis could represent a manifestation of temporal arteritis. EXEGESIS: A 75-year-old-woman was admitted for progressive physical deterioration which had been evolving for three months, associated with fever, frontotemporal cephalalgia and severe biological inflammatory syndrome. Chest X-ray reveals a cardiomegaly and suggests a pericarditis, which was rapidly confirmed by echocardiogram. Temporal artery biopsy concludes to the diagnosis of a giant cell arteritis. Steroids treatment is prescribed, leading to a rapid regression of the inflammatory state and the pericarditis without relapse after 6 months of follow-up. CONCLUSION: Only prospective studies on systematic echocardiography when faced with the diagnosis of giant cell arteritis, whatever clinical symptoms, will enable to appreciate the prevalence and prognosis value of this manifestation. Moreover, temporal artery analysis seems to be justified when faced with a sub-acute or chronic "idiopathic" inflammatory pericarditis occurring in the elderly patient. Physiopathogeny is unknown but some hypothesis can be proposed: inflammatory cytokines storm, immune complexes deposition, giant cell vasculitis of pericardial arteries or inflammatory interstitial lesion of the pericardium with or without granuloma. PMID- 17335943 TI - Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV(89.6P) challenge in rhesus macaques. AB - Plasmid-based IL-12 has been demonstrated to successfully enhance the immunogenicity of DNA vaccines, thus enabling a reduction of the amount of DNA required for immunization. IL-15 is thought to affect the maintenance and enhance effector function of CD8(+) memory T cells. Since the ability to elicit a long term memory response is a desirable attribute of a prophylactic vaccine, we sought to evaluate the ability of these plasmid-based cytokines to serve as vaccine adjuvants in rhesus macaques. Macaques were immunized with plasmid DNA encoding SIVgag in combination with plasmid IL-12, IL-15, or a combination of IL 12 and IL-15. The plasmid-based cytokines were monitored for their ability to augment SIVgag-specific cellular and humoral immune responses and to alter the clinical outcome following pathogenic SHIV(89.6P) challenge. Macaques receiving SIVgag pDNA in combination with plasmid IL-12 alone, or in combination with plasmid IL-12 and IL-15, demonstrated significantly elevated cell-mediated and humoral immune responses resulting in an improved clinical outcome following virus challenge compared to macaques receiving SIVgag pDNA alone. Macaques receiving SIVgag pDNA in combination with plasmid IL-15 alone demonstrated minor increases in cell-mediated and humoral immune responses, however, the clinical outcome following virus challenge was not improved. These results have important implications for the continued development of plasmid DNA vaccines for the prevention of HIV-1 infection. PMID- 17335944 TI - Immunoregulatory activity by daucosterol, a beta-sitosterol glycoside, induces protective Th1 immune response against disseminated Candidiasis in mice. AB - In the present study, we investigated immunomodulatory effect of daucosterol, a beta-sitosterol glycoside, against disseminated candidiasis caused by Candida albicans. Results showed that direct interaction of daucosterol with C. albicans yeast cells resulted in no growth-inhibition by in vitro susceptibility analysis. In contrast, mice given daucosterol (DS) intraperitoneally before intravenous challenge with live C. albicans yeast cells survived longer than DS-untreated control mice against disseminated candidiasis (P<0.05). By assessment of the fungal CFU in kidneys, DS-treated mice before the challenge developed about 81% fewer kidney CFU than untreated controls. This protection was removable by pretreatment of mice with anti-CD4+ antibody before the DS-treatment and challenge with the yeast. However, the protection was transferable by the CD4+ T cells from DS-treated mice not infected with the yeast. ELISA analysis revealed there were predominant production of IFNgamma and IL-2 cytokines as compared to IL-4, and IL-10 productions in DS-treated mice. By treatment of DS-given mice with anti-mouse IFNgamma, the protection was also abolished. Our studies show that DS protects mice against disseminated candidiasis by the CD4+ Th1 immune response. PMID- 17335945 TI - Traditional postpartum practices of women and infants and the factors influencing such practices in South Eastern Turkey. AB - OBJECTIVE: to gain an understanding of traditional postpartum practices for women and babies, and to investigate the factors influencing such practices. DESIGN: descriptive study. SETTING: Maternity and Children's Hospital in Adiyaman city, Turkey. PARTICIPANTS: 273 women who gave birth at the Maternity and Children's Hospital in Adiyaman city from March to June 2004. FINDINGS: more than half of the 273 women (55.7%) were aged between 25 and 32 years (mean 27.85, standard deviation [SD] 5.45). A total of 22.3% of women were illiterate, and most were unemployed. The most popular practices among new mothers were eating a kind of dessert, called 'Bulamac' (82.8%). A number of women (69.6%) drank a mixture of grape molasses and butter, 64.5% had their abdomen tightly wrapped, 62.6% were not left alone at home, and more than half of the women (57.9%) avoided sexual intercourse for 40 days after giving birth. Nearly, half of the women (45.4%) fed their babies with water containing sugar just after the birth, and 77.1% of women kept their babies' umbilical cord in a special place. Afterwards, the mothers threw the cords into a river or they buried them in the grounds of a mosque or a school. Most of the mothers (89%) reported that they covered their babies with a yellow cloth in order to protect them from jaundice. A relationship between traditional postpartum practices and demographic characteristics of women was observed. The women's mothers and mothers-in-law (66.7%) usually encouraged such practices. KEY CONCLUSIONS: postpartum care of women and their babies are important cultural practices. Some of these practices may have harmful effects on women and their babies. IMPLICATIONS FOR PRACTICE: it is important to gain an understanding of cultural beliefs and traditional practices relating to the postpartum care of women and their babies. Midwives and nurses should discuss these findings and their implications when they educate new mothers and their families about contemporary methods of postnatal maternal and infant care. PMID- 17335946 TI - Scaphoid bone bruising--probably not the precursor of asymptomatic non-union of the scaphoid. AB - The MRI finding of bone marrow oedema, without fracture, following trauma to the scaphoid has been called a 'bone bruise'. A similar injury is found in the knee, considered benign and managed conservatively. In the scaphoid, there is the concern that this lesion may lead to scaphoid non-union. This study addresses that concern. The clinical and radiological findings of 41 patients with a scaphoid bone bruise on MRI are described, an MRI classification system proposed and clinical outcomes investigated. Patients were immobilised for 6 weeks. At 3 months, 8 remained symptomatic and had repeat MRI. Four of these showed complete resolution of the bruise, the others improvement. At 6 months, 2 of the 8 complained of minor, intermittent discomfort but progressed to resolution of symptoms. This study suggests that the scaphoid bone bruise is a benign injury with predictable recovery and is unlikely to result in long-term morbidity in the form of non-union. PMID- 17335947 TI - The effect of the severity of the Dupuytren's contracture on the function of the hand before and after surgery. AB - This study investigated the effect on the power and function of the hand of loss of finger(s) extension, number of fingers involved and the patient's age in Dupuytren's disease and the influence of improvement of finger extension and the patient's age on these variables after surgery. Median values at presentation included total loss of extension 80 degrees, total grip strength 41 kg and DASH score 54. Twelve months postoperatively, the median value of total loss of extension decreased to 10 degrees and the DASH score to 32 (both significant improvements). Grip strength decreased slightly to 40 kg. The severity of the contracture had no significant effect on function but had a significant negative effect on power. The number of fingers involved affected neither function nor power. The age of the patient did not influence function of the hand. However, older patients experienced less functional benefit from surgery. The improvement of finger extension following surgery had significant beneficial effect on function, but no effect on power. PMID- 17335948 TI - Social deprivation and hand injury. AB - This study investigated the relationship between socioeconomic deprivation and the incidence, patterns of injury, process of care and outcome of hand trauma using data collected prospectively on 1234 injuries presented during six months. The Index of Multiple Deprivation 2004 was derived from census data and postcodes. Socioeconomic deprivation is significantly associated with hand trauma. The odds ratio for suffering hand injuries in the most deprived quintile is 1.6 (SE 0.09 95% CI 1.45, 1.83) compared to the least deprived quintile. This is most marked among older children and adults. Fractures, sprains and ligament injuries showed the strongest association with the degree of deprivation. Injuries related to sport were not associated with deprivation. Surgical time utilised is greater in more deprived patients and their self reported physical outcome is worse. Hand surgery units working in areas of high socioeconomic deprivation will have higher trauma workloads and unit costs. Social deprivation may also influence physical outcomes. PMID- 17335950 TI - Effects of imagery training on cognitive performance and use of physiological measures as an assessment tool of mental effort. AB - The effectiveness of motor imagery training on cognitive performance was examined and the physiological mechanisms involved in the contribution of mental practice to motor learning were considered. The subject's mental effort during motor imagery was assessed by using psychophysiological measures and particularly eye blink activity as an 'indirect' measurement of subjects' attention. An electronic flight simulation program (Multiple Attribute Task Battery--MATB) was used to assess performance. Twenty healthy volunteers participated in the study divided in two groups: the control group and the imagery-training group. The subjects of the imagery group were asked for additional imagery training. The subjects of the actual performing group were asked additionally to passively observe the task in order to have equal time of exposure to the task. Performance scores and physiological parameters such as heart rate, respiratory rate, eye blinking activity and muscular activity were recorded during all sessions. The results revealed significantly higher performance level of the imagery-training group than the control group. Heart rate and respiratory rate significantly increased during imagery sessions compared to rest. A slight electromyographic activity was observed during the imagination of movement. Our findings support the notion that mental practice improves motor performance in a task where spatiotemporal or dynamic control of the action is highly required. The effects of mental practice on motor performance could be explained by the existence of a top-down mechanism based on the activation of a central representation of the movements, since the vegetative activation during motor imagery seems to be centrally controlled. PMID- 17335951 TI - Serotonin transporter density and anxiolytic-like effects of antidepressants in mice. AB - BACKGROUND: Chronic treatment with the dual serotonin/noradrenaline reuptake inhibitor (SNRI) duloxetine reduces the density of serotonin transporter sites in cortex and engenders an anxiolytic-like response. To determine the reproducibility of these effects and their generality to other antidepressants we compared the effects of chronic duloxetine treatment with another SNRI, venlafaxine, and two selective serotonin reuptake inhibitors, paroxetine and fluoxetine. METHODS: Separate groups of mice were administered vehicle, fluoxetine (15 mg/kg), paroxetine, duloxetine or venlafaxine (10 mg/kg) perorally twice daily for 28 days and tested in the mouse zero-maze and in motility cages on days 21 and 22, respectively, to determine effects on anxiety and motor activity. On day 28 brains were analysed for serotonin transporter (SERT) density in cortex and noradrenaline transporter (NET) density in cortex and hippocampus. RESULTS: Duloxetine and fluoxetine both reduced SERT density in cortex and induced anxiolytic-like effects. Paroxetine had an identical profile, but it is unclear if this drug down-regulated the SERT since extensive washing of cortical tissue did not remove all drug. Venlafaxine had no effect on behavioural or biochemical parameters. Only duloxetine reduced NET density in cortex, although not hippocampus. CONCLUSIONS: The reduction in SERT density and anxiolytic-like effects with duloxetine, fluoxetine and, potentially, paroxetine suggest that down-regulation of the SERT may be a relevant mechanism in therapeutic response to these antidepressants. PMID- 17335952 TI - Cadmium stimulates MAPKs and Hsp27 phosphorylation in bovine adrenal chromaffin cells. AB - Cadmium (Cd(2+)) is a common environmental pollutant, which is widely used in industry and is a constituent of tobacco smoke. Exposure to this heavy metal has been linked to a wide range of detrimental effects on mammalian cells. In this study, the action of Cd(2+) on protein phosphorylation in bovine adrenal chromaffin cells (BACCs) was examined. Cells were incubated with (32)Pi in the presence of Cd(2+) (1-50 microM) and proteins were separated by one- or two dimensional electrophoresis. An increase in the phosphorylation of BACCs proteins, without changing cell viability, was observed in response to Cd(2+) (5 50 microM). Particularly at three spots, with molecular weight of 25kDa and isoeletric point range 4.0-4.5, which were identified as phosphorylated isoforms of the heat shock protein of 27kDa (Hsp27). Phosphorylation of the p38(MAPK), a member of mitogen-activated protein kinase (MAPK) family, was stimulated by Cd(2+) over the same concentration range and it was the major upstream protein kinase involved in the phosphorylation of all three spots of Hsp27. Cd(2+) also stimulated the phosphorylation of other MAPK family member, the extracellular signal-regulated kinase (ERK)-1/2. Therefore, primary adrenal chromaffin cells are a target for Cd(2+) and both the ERK1/2 and the p38(MAPK) are activated. Additionally, Hsp27 is highly phosphorylated in response to the metal exposure, due to p38(MAPK) activation. These biochemical effects of Cd(2+) might disrupt the normal secretory function of these cells. PMID- 17335953 TI - Endocytosis of the dermatan sulfate proteoglycan decorin utilizes multiple pathways and is modulated by epidermal growth factor receptor signaling. AB - Human skin fibroblasts efficiently internalize the matrikine decorin by receptor mediated endocytosis, however, very little is known about its intracellular trafficking routes up to lysosomal degradation. In an in vitro system measuring uptake and degradation of [(35)S]sulfate-labeled decorin, endocytosis was blocked by 46% when clathrin assembly/disassembly was inhibited using chlorpromazine. Pharmacological inhibition of EGF receptor signaling caused 34% reduction of decorin uptake, whereas inhibition of the IGF receptor had no effect. Using confocal immunofluorescence microscopy, we determined that only about 5-10% of internalized decorin colocalized with the EGFR. Thus, uptake depends on EGFR signaling rather than trafficking along the same pathway. Decorin passes through early endosomes towards trafficking to lysosomes, since more than 50% of decorin colocalized with EEA1. Moreover, inhibition of endosomal fusion by wortmannin caused a profound inhibition of decorin endocytosis. Overexpression of the clathrin-binding Hrs protein, which has previously been shown to inibit EGFR degradation blocked the degradation of decorin. Cholesterol depletion by filipin inhibited uptake of decorin by 34%, however, nearly no intracellular colocalization was found between decorin and caveolin-1. The combined use of filipin and chlorpromazine had an additive inhibitory effect on decorin endocytosis. Moreover, chlorpromazine diverted decorin from the chlorpromazine sensitive pathway to an alternative uptake route. The CD44/hyaluronan pathway was excluded as an endocytic route for decorin. Our observations indicate that decorin is taken up by more than one endocytic pathway. Of note, lipid-raft dependent EGFR signaling modulates decorin uptake, suggesting the presence of a potential feedback regulation mechanism for desensitization of signaling events mediated by decorin. PMID- 17335955 TI - Anti-Mullerian hormone levels during hormonal contraception in women with polycystic ovary syndrome. AB - OBJECTIVE: The use of oral contraceptive (OC) pills alters the characteristic features of polycystic ovary syndrome (PCOS) complicating the diagnosis of this disease. Anti-Mullerian hormone (AMH) levels are high in PCOS patients and are stable throughout the menstrual cycle in healthy subjects. This study examined the influence of hormonal suppression with OC therapy on the serum AMH levels in women with PCOS and with normal menstrual cycles. STUDY DESIGN: Thirty women with PCOS and 15 women with normal menstrual cycles were enrolled in this prospective study. Serum was collected from the subjects during the early follicular phase of the menstrual cycle and after the sixth cycle of oral contraceptive therapy, and stored frozen until assayed. The effect of OC therapy on the serum AMH, estradiol (E(2)), luteinizing hormone (LH), follicle-stimulating hormone (FSH), free testosterone, total testosterone, and dehydroepiandrosterone sulfate (DHEA-S) levels was studied. In addition, ovarian volume and follicle count were assessed. RESULTS: The serum AMH levels in PCOS patients were significantly higher than in healthy women at baseline (+/-S.D.; 5.49+/-2.26 and 1.93+/-0.51 ng/ml, respectively; p=0.001). After six cycles of OC therapy, no significant changes in the AMH levels were observed in either the PCOS patients or normally cycling women. Ultrasound showed significant reductions in ovarian volume and follicle number and size at 6 months in both groups. CONCLUSION: Although significant reductions were observed in ovarian volume and follicle number, 6 months of contraceptive therapy did not change the serum AMH concentration in either group. AMH may be considered a new marker in PCOS patients who are already on contraceptive treatment. PMID- 17335956 TI - Pelvic actinomycosis 17 years after hysterectomy. PMID- 17335957 TI - Inter-municipal cooperation for wastewater treatment: case studies from Israel. AB - Since the beginning of the 1990s, local authorities in Israel have been engaged in promoting advanced Wastewater Treatment Plant (WWTP) projects throughout the country, resulting in the "wastewater treatment revolution" of the 1990s. These achievements are extremely important in the water-scarce country, as untreated or partially treated wastewater has become a major source of pollution of Israel's fresh-water resources, and reuse of high-quality effluents can expand the national water potential. Many of these projects are regional schemes based on a central WWTP, serving a few neighboring municipalities. This paper presents two case studies of such regional cooperation: the "Karmiel Region Union of Towns for Sewage Treatment" and the "Treatment and Reuse of Wastewater in the area of the Hadera Stream, Ltd." corporation. The findings suggest that regional cooperation can be an efficient tool in promoting advanced wastewater treatment, and has several advantages: an efficient use of limited resources (financial and land); balancing disparities between municipalities (size, socio-economic features, consciousness and ability of local leaders); and reducing spillover effects. However, some problems were reported in both cases and should be addressed. PMID- 17335958 TI - Application of a long-path differential optical absorption spectrometer (LP-DOAS) on the measurements of NO(2), SO(2), O(3), and HNO(2) in Gwangju, Korea. AB - A differential optical absorption spectrometer (DOAS) technique has been applied to monitor airborne trace pollutants including NO(2), SO(2), O(3), and HNO(2) in the ultraviolet (UV) region (290-350 nm) over a 1.5 km beam path (two ways) during an intensive measurement campaign held at Gwangju, Korea (March 2002). Their mean mixing ratios (and standard deviations) were computed as 11.3 (8.8), 1.9 (1.7), 17.1 (19.3), and 0.5 (0.4)ppbv, respectively. As a means to evaluate the performance of the long-path DOAS (LP-DOAS) system with conventional point monitoring systems (PMS), correlation analysis was conducted between the two data sets. These data sets were then inspected to account for the influence of the environmental conditions on the correlation strength between the two systems, especially with respect to light level and wind speed. To facilitate the comparison, correlation analyses were conducted after dividing the data sets for those parameters into several classes. The strength of the correlations between DOAS and meteorological parameters was also examined to evaluate their effects on the DOAS performance. It was found that, among the four pollutant species, O(3) is the most sensitive to changes in meteorological conditions in relation with atmospheric mixing conditions. The overall results of our study indicate that open-path monitoring techniques can be used to effectively diagnose air quality and be substituted for the conventional point monitoring methods with the proper consideration of those parameters affecting the DOAS sensitivity (e.g., light level and wind speed). PMID- 17335959 TI - Editorial comment on: extracorporeal magnetic stimulation is of limited clinical benefit to women with idiopathic detrusor overactivity: a randomized sham controlled trial. PMID- 17335960 TI - Rebuttal from authors re: Peter Albers. Quality criteria of laparoscopic nephroureterectomy. Eur Urol. 2007;51:1481-2. PMID- 17335961 TI - Outcomes of surgery of female urethral diverticula classified using magnetic resonance imaging. AB - OBJECTIVES: We evaluated the surgical outcomes of transvaginal diverticulectomies classified using magnetic resonance imaging (MRI). METHODS: We evaluated 30 women (mean age: 46.4 yr; range: 31-73 yr) who were followed up for at least 12 mo after urethral diverticulectomies (mean follow-up: 29 mo; range: 12-93 mo). Characteristics of urethral diverticula were confirmed before surgery by MRI. Diverticula were classified as simple, U-shaped, or circumferential according to MRI features. Transvaginal excisions of urethral diverticula were performed using vaginal flaps and three-layer closures. Cure was defined as the absence of a diverticulum and symptoms. RESULTS: Seventeen cases (57%) had simple diverticula, three (10%) had U-shaped diverticula, and 10 (33%) had circumferential diverticula. After the first operation, 23 cases (77%) were cured. None of the simple diverticula recurred, but 33% of the U-shaped and 60% of the circumferential diverticula did recur. Of the seven recurrent cases, three did not require a second operation because their symptoms resolved. Of the four cases that underwent a second operation, three were cured and one was cured after two additional operations. The success rate for circumferential diverticula after initial diverticulectomies was less than that of simple or U-shaped diverticula (p<0.05). Location, size, and multiplicity of urethral diverticula did not affect the surgical outcome (p>0.05). CONCLUSIONS: Transvaginal diverticulectomy is effective for treatment of female urethral diverticula. For circumferential urethral diverticula, however, surgical procedures should be adapted to achieve complete resections of the diverticulum. PMID- 17335962 TI - Extracorporeal magnetic stimulation is of limited clinical benefit to women with idiopathic detrusor overactivity: a randomized sham controlled trial. AB - OBJECTIVES: To observe the effect of both acute and medium-term magnetic stimulation of the pelvic floor on detrusor function amongst women with idiopathic detrusor overactivity (IDO). METHODS: Two separate studies were undertaken amongst women with a sole diagnosis of IDO. The first study assessed the acute effect of magnetic stimulation (provided by Neocontrol ) on detrusor function during the filling phase of standard cystometry. Multiple filling cycles were performed with stimulation at a different key moment in each. This was done to establish that the device could influence the detrusor. Subsequently, a randomized sham control trial was performed to assess clinical efficacy. A total of 20 treatments, each of 20 minutes duration, were administered over six weeks with follow-up six weeks thereafter. Half the patients received therapy from a genuine device, the others receiving fake treatment on an identical looking/sounding sham device. The sham device contained a deflector plate to degrade the magnetic field and was located in a separate room. Outcome measures included changes in a 24 hour fluid volume chart, urine loss (24 hour pad test) and quality of life instruments. RESULTS: Amongst 10 patients receiving stimulation during cystometry, volume at first involuntary detrusor contraction during filling rose from a median value of 240ml (Inter-quartile range (IQR) 210 300) to 285ml (IQR 231-320), p = 0.03 and maximum detrusor pressure decreased from 40cm water (IQR 34-45) to 33cm water (IQR 25-41), p<0.01. The RCT was completed by 29 of 44 (66%) recruits. Of these, 15 of 29 (52%) received active treatment and 14 of 29 (48%) sham therapy. Active therapy significantly reduced the number of urge episodes per day, p<0.01. With respect to baseline, actively treated patients experienced significant reduction in voids per day and quality of life but this trend did not reach significance when compared to the sham group, partly due to unexpected difficulty in recruitment which yielded an underpowered sample size for these outcome measures. CONCLUSIONS: Magnetic stimulation reduces detrusor contractility in the acute phase of administration. Although the treatment was well tolerated and urge episodes reduced following prolonged therapy, no statistically significant improvement was observed in quality of life indices or measured 24 hour urinary loss. The treatment cannot be recommended for women with IDO. PMID- 17335963 TI - Editorial comment on: extracorporeal magnetic stimulation is of limited clinical benefit to women with idiopathic detrusor overactivity: a randomized sham controlled trial. PMID- 17335964 TI - Role of signal-dependent noise during maintenance of isometric force. AB - The assumption that signal-dependent noise during isometric force production controls the stabilization of voluntary isometric force is considered. To verify the assumption the trajectory of isometric force is decomposed into voluntary and involuntary components and the mathematical model describing the relationship between them is developed. It is shown that the integral of an involuntary component (signal-dependent noise) plays the role of the controlling parameter realizing the stabilization of a voluntary component. The stabilization is carried out both in the absence and in the presence of visual feedback. Changes of experimental conditions are accompanied by essential changes in the amplitude of the involuntary component oscillations. PMID- 17335965 TI - The Par6alpha/aPKC complex regulates Akt1 activity by phosphorylating Thr34 in the PH-domain. AB - A single nucleotide polymorphism in the partitioning defective protein-6alpha (Par6alpha) promoter is coupled with lower Par6alpha expression and better insulin sensitivity, whereas overexpression of Par6alpha in C2C12 myoblasts inhibits insulin-induced protein kinase B/Akt1 activation and glycogen synthesis. Here we show that a direct interaction of Par6alpha with atypical protein kinase C (aPKC) is crucial for this inhibition. A DeltaPB1-Par6alpha deletion mutant that does not interact with aPKC neither increased aPKC activity nor interfered with insulin-induced Akt1 activation in C2C12 cells. Further, T34 phosphorylation of Akt1 through aPKC is important for inhibition of Akt1. When Par6alpha was overexpressed, activation of wild-type Akt1 (-59.3%; p=0.049), but not T34A-Akt1 (+2.9%, p=0.41) was reduced after insulin stimulation. The resistance of T34A Akt1 to Par6alpha/aPKC-mediated inhibition was also reflected by reconstitution of insulin-induced glycogen synthesis. In summary, Par6alpha-mediated inhibition of insulin-dependent glycogen synthesis in C2C12 cells depends on the direct interaction of Par6alpha with aPKC and on aPKC-mediated T34 phosphorylation of Akt1. PMID- 17335966 TI - Biotransformation and metabolic response of cyanide in weeping willows. AB - Biotransformation and metabolic responses of plants to cyanide were investigated using pre-rooted plants of weeping willows (Salix babylonica L.) grown hydroponically in growth chambers and treated with potassium cyanide. Various physiological parameters of the plants were monitored to determine toxicity from exogenous cyanide exposure. Cyanide doses used in this study showed growth promoting effects on plants, exhibiting higher measured values of transpiration rates, chlorophyll contents and soluble protein contents compared with the non treated control plants. Superoxide dismutases (SOD), catalase (CAT) and peroxidase (POD) activities in leaves showed a slight change to cyanide application in most treatments. Of all selected parameters, soluble proteins of plants were the most sensitive indicator to cyanide application. Almost all applied cyanide was removed from the hydroponic solution in the presence of plants in all treatment groups. Small amounts of cyanide were detected in the plant tissues. Recovery of cyanide in different compartments of plants varied significantly, root being the dominant sink for cyanide accumulation. Mass balance studies showed that >97% of the applied cyanide was metabolized during transport through weeping willows and the metabolic rates of cyanide by plants were linearly increased with increasing of cyanide applied in the growth media. Results from this study indicated that neither visible toxic symptom nor metabolic lesion was observed for the plants after 192h of exposure, largely due to the well-established detoxification systems in willows. These findings suggest that cyanide has a beneficial role in plants and phytoremediation is a desirable solution of treating environmental sites contaminated with cyanide. PMID- 17335967 TI - The assistance of microwave process in sludge stabilization with sodium sulfide and sodium phosphate. AB - After industrial wastewater sludge passed through an acid-extraction process to reclaim most of the copper ions in it, the residue may still need to be treated by stabilization technologies. The common method for the stabilization of hazardous waste in Taiwan is by cement solidification. However, this method has the disadvantage of an increase in waste volume. In this study, it was tried to combine the advantages of sulfur anions and phosphate anions with the characteristics of microwave energy to offer a new method which can avoid the disadvantage of cement solidification. From the results, it was found that the assistance of heating in sludge stabilization with additives was effective. Huge amounts of additives were saved. Compared with the assistance of the traditional electrical-heating in sludge stabilization with additives, that of the microwave process saved much time and was more powerful. However, when the reaction time was longer, a re-leaching situation would occur. The hybrid microwave process, a procedure of leading an inert gas into the microwave process, could overcome the disadvantage of the microwave process with regard to the long reaction time. Finally, a modified hybrid microwave process which reduced the use of gas was performed and recommended. PMID- 17335968 TI - Reliable estimation of performance of explosives without considering their heat contents. AB - In this paper, a new approach is introduced to calculate detonation pressure of large class of explosives based elemental composition and specific structural groups rather than using their heats of formation. It is shown here how the loading density, atomic composition and some structural parameters can be integrated into an empirical formula for predicting the detonation pressure of pure and explosive formulations over a wide range of loading densities. The results show good agreement with experimental values so that the deviations are within about experimental errors. The calculated values of new method are also compared with the computed results obtained by complex computer code using BKWR and BKWS equations of state. Predicted detonation pressures have root-mean-square (rms) deviation for new method, BKWR and BKWS equations of state are 6.5, 11.7 and 7.4kbar, respectively. PMID- 17335969 TI - Comparison of Amberlite IR 120 and dolomite's performances for removal of heavy metals. AB - The presence of heavy metals in the environment is major concern due to their toxicity. Contamination of heavy metals in water supplies has steadily increased over the last years as a result of over population and expansion of industrial activities. A strong cation-exchange resin, Amberlite IR 120 and a natural zeolite, dolomite were used for the removal of lead(II) and cadmium(II). The optimum conditions were determined in a batch system as concentration range was between 5 and 100 mg/L, pH range between 1 and 8, contact time between 5 and 90 min, and the amount of adsorbent was from 0.1 to 1g. A constant stirring speed, 2000 rpm, was chosen during all of the experiments. The optimum conditions were found to be a concentration of 20 mg/L, pH of 5, contact time of 60 min and 0.5 g of adsorbent. Also, for investigation of exchange equilibria different amounts of ion exchange resin and dolomite were contacted with a fixed volume and concentration of a heavy metal bearing solutions. Sorption data have been interpreted in terms of Langmuir and Freundlich equations. The effect of adsorption temperature on the heavy metals adsorption onto dolomite was investigated at three different temperatures (20, 40 and 60 degrees C). Thermodynamic parameters were calculated. The results obtained show that the Amberlite IR 120 strong cation-exchange resin and dolomite performed well for the removal of these heavy metals. As a low cost adsorbent, dolomite can preferable for removal of heavy metals from wastewaters. PMID- 17335970 TI - 5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. AB - Glioblastoma is the most common astrocytic brain tumor in humans. Current therapies for this malignancy are mostly ineffective. Photodynamic therapy (PDT), an exciting treatment strategy based on activation of a photosensitizer, has not yet been extensively explored for treating glioblastoma. We used 5-aminolevulinic acid (5-ALA) as a photosensitizer for PDT to induce apoptosis in human malignant glioblastoma U87MG cells and to understand the underlying molecular mechanisms. Trypan blue dye exclusion test showed a decrease in cell viability after exposure to increasing doses of 5-ALA for 4h followed by PDT with a broad spectrum blue light (400-550 nm) at a dose of 18J/cm(2) for 1h and then incubation at 37 degrees C for 4h. Following 0.5 and 1mM 5-ALA-based PDT (5-ALA-PDT), Wright staining and ApopTag assay showed occurrence of apoptosis morphologically and biochemically, respectively. After 5-ALA-PDT, down regulation of nuclear factor kappa B (NFkappaB) and baculovirus inhibitor-of-apoptosis repeat containing-3 (BIRC-3) protein indicated inhibition of survival signals. Besides, 5-ALA-PDT caused increase in Bax:Bcl-2 ratio and mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF). Activation of calpain, caspase-9, and caspase-3 occurred in course of apoptosis. Calpain and caspase-3 activities cleaved alpha spectrin at specific sites generating 145kD spectrin breakdown product (SBDP) and 120kD SBDP, respectively. The results suggested that 5-ALA-PDT induced apoptosis in U87MG cells by suppression of survival signals and activation of proteolytic pathways. Thus, 5-ALA-PDT can be an effective strategy for inducing apoptosis in glioblastoma. PMID- 17335971 TI - The effects of frequency altered feedback on reading comprehension abilities of normal and reading disordered children. AB - The effects of frequency altered feedback (FAF) on the reading comprehension levels and error types of normal children and children with reading disorders were examined. Participants read aloud third, sixth, and ninth grade level material in non-altered auditory feedback (NAF) and FAF conditions. Comprehension improved significantly when the reading disordered children read aloud under the FAF listening condition, regardless of the reading level. Significant differences did not occur in reading comprehension for the normal readers under NAF versus FAF conditions. Reading disordered children produced significantly more reading errors as compared to the normal reading children under the NAF listening condition. No significant difference was found in reading errors between groups when reading under FAF regardless of the reading level, suggesting that the FAF signal produced a facilitory effect on reading errors in the reading disordered children. Theoretically, the FAF signal may have activated those cortical regions responsible for the relationship that has been shown to exist between lexical encoding and decoding of verbal and written material, respectively. PMID- 17335972 TI - Spinal CGRP1 receptors contribute to supraspinally organized pain behavior and pain-related sensitization of amygdala neurons. AB - CGRP receptor activation has been implicated in peripheral and central sensitization. The role of spinal CGRP receptors in supraspinal pain processing and higher integrated pain behavior is not known. Here we studied the effect of spinal inhibition of CGRP1 receptors on supraspinally organized vocalizations and activity of amygdala neurons. Our previous studies showed that pain-related audible and ultrasonic vocalizations are modulated by the central nucleus of the amygdala (CeA). Vocalizations in the audible and ultrasonic range and hindlimb withdrawal thresholds were measured in awake adult rats before and 5-6h after induction of arthritis by intra-articular injections of kaolin and carrageenan into one knee. Extracellular single-unit recordings were made from neurons in the latero-capsular division of the CeA (CeLC) in anesthetized rats before and after arthritis induction. CGRP1 receptor antagonists were applied to the lumbar spinal cord intrathecally (5 microl/min) 6h postinduction of arthritis. Spinal administration of peptide (CGRP8-37, 1 microM) and non-peptide (BIBN4096BS, 1 microM) CGRP1 receptor antagonists significantly inhibited the increased responses of CeLC neurons to mechanical stimulation of the arthritic knee but had no effect under normal conditions. In arthritic rats, the antagonists also inhibited the audible and ultrasonic components of vocalizations evoked by noxious stimuli and increased the threshold of hindlimb withdrawal reflexes. The antagonists had no effect on vocalizations and spinal reflexes in normal rats. These data suggest that spinal CGRP1 receptors are not only important for spinal pain mechanisms but also contribute significantly to the transmission of nociceptive information to the amygdala and to higher integrated behavior. PMID- 17335973 TI - A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. AB - Between 40% and 60% of Americans use complementary and alternative medicine to manage medical conditions, prevent disease, and promote health and well-being. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been used to treat joint pain associated with several inflammatory conditions. We conducted a meta analysis of 17 randomized, controlled trials assessing the pain relieving effects of omega-3 PUFAs in patients with rheumatoid arthritis or joint pain secondary to inflammatory bowel disease and dysmenorrhea. Meta-analysis was conducted with Cochrane Review Manager 4.2.8. for six separate outcomes using standardized mean differences (SMDs) as a measure of effect size: (1) patient assessed pain, (2) physician assessed pain, (3) duration of morning stiffness, (4) number of painful and/or tender joints, (5) Ritchie articular index, and (6) nonselective nonsteroidal anti-inflammatory drug consumption. Supplementation with omega-3 PUFAs for 3-4 months reduces patient reported joint pain intensity (SMD: -0.26; 95% CI: -0.49 to -0.03, p=0.03), minutes of morning stiffness (SMD: -0.43; 95% CI: -0.72 to -0.15, p=0.003), number of painful and/or tender joints (SMD: -0.29; 95% CI: -0.48 to -0.10, p=0.003), and NSAID consumption (SMD: -0.40; 95% CI: 0.72 to -0.08, p=0.01). Significant effects were not detected for physician assessed pain (SMD: -0.14; 95% CI: -0.49 to 0.22, p=0.45) or Ritchie articular index (SMD: 0.15; 95% CI: -0.19 to 0.49, p=0.40) at 3-4 months. The results suggest that omega-3 PUFAs are an attractive adjunctive treatment for joint pain associated with rheumatoid arthritis, inflammatory bowel disease, and dysmenorrhea. PMID- 17335974 TI - Using visual illusion to reduce at-level neuropathic pain in paraplegia. AB - Neuropathic pain after spinal cord injury is not well understood and is difficult to treat. One possible cause is mismatch between motor commands and sensory feedback. This two-part study in five paraplegic patients investigated whether a visual illusion aimed to correct this mismatch reduces pain. In study 1, patients undertook three conditions: (i) virtual walking: with a mirror placed in front of a screen, patients aligned their own upper body with a film of a lower body walking. Patients imagined walking and 'watched themselves' walk; (ii) guided imagery; (iii) watching a film. One patient withdrew from virtual walking because of distress. For all patients, the mean (95% CI) decrease in pain (100 mm VAS) was 42 mm (approximately 65%) (11-73 mm) for virtual walking, 18 mm (4-31 mm) for guided imagery and 4mm (-3 to 11 mm) for watching the film. Mean (95% CI) time to return to pre-task pain was 34.9 min (20.1-49.8 min) for virtual walking; 13.9 min (-0.9 to 28.8 min) for the guided imagery and 16.3 min (1.5-31.2 min) for the film. To investigate its clinical utility, four patients underwent virtual walking every weekday for 3 weeks. Mean (95% CI) decrease in pain was 53 mm (45 61 mm) at post training and 43 mm (27-58 mm) at 3-month follow-up. Virtual walking may be a viable treatment for pain after spinal cord injury. A clinical trial seems warranted. PMID- 17335975 TI - Helplessness and loss as mediators between pain and depressive symptoms in fibromyalgia. AB - This study evaluated the contribution of condition-specific helplessness and loss to depression in fibromyalgia (FM). Two models were tested. The first model examined whether loss, measured by the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) Interference Scale, would mediate the relationship between disability and depression. The second model determined whether condition-specific helplessness and loss would mediate the relationship between pain and depression with disability controlled. Eighty patients with confirmed diagnoses of FM were recruited throughout Southern California from general medical clinics, newspaper advertisements, and rheumatology practices. The study design was cross-sectional, using self-report, observational, and interview measures. A composite measure of depression was adopted, consisting of the Center for Epidemiological Studies Depression Scale and the Hamilton Rating Scale for Depression. Hierarchical multiple regression analyses were conducted using a path analytic framework to examine each model. In Model 1, loss fully mediated the relationship between disability and depression. In Model 2, condition-specific helplessness mediated the relationship between pain and depression, but the contribution of loss was not significant. The findings confirm the importance of helplessness and demonstrate that the cognitive meaning of having FM plays a more central role in predicting depressive symptomatology than illness-related stressors, such as pain or disability. PMID- 17335976 TI - Systemic administration of monosodium glutamate elevates intramuscular glutamate levels and sensitizes rat masseter muscle afferent fibers. AB - There is evidence that elevated tissue concentrations of glutamate may contribute to pain and sensitivity in certain musculoskeletal pain conditions. In the present study, the food additive monosodium glutamate (MSG) was injected intravenously into rats to determine whether it could significantly elevate interstitial concentrations of glutamate in the masseter muscle and whether MSG administration could excite and/or sensitize slowly conducting masseter afferent fibers through N-methyl-D-aspartate (NMDA) receptor activation. The interstitial concentration of glutamate after systemic injection of isotonic phosphate buffered saline (control) or MSG (10 and 50mg/kg) was measured with a glutamate selective biosensor. The pre-injection baseline interstitial concentration of glutamate in the rat masseter muscle was 24+/-11 microM. Peak interstitial concentration after injection of 50mg/kg MSG was 63+/-18 microM and remained elevated above baseline for approximately 18 min. In vivo single unit recording experiments were undertaken to assess the effect of MSG (50mg/kg) on masseter afferent fibers. Injection of MSG evoked a brief discharge in one afferent fiber, and significantly decreased ( approximately 25%) the average afferent mechanical threshold (n=10) during the first 5 min after injection of MSG. Intravenous injection of ketamine (1mg/kg), 5 min prior to MSG, prevented the MSG-induced decreases in the mechanical threshold of masseter afferent fibers. The present results indicate that a 2- to 3-fold elevation in interstitial glutamate levels in the masseter muscle is sufficient to excite and induce afferent mechanical sensitization through NMDA receptor activation. These findings suggest that modest elevations of interstitial glutamate concentration could alter musculoskeletal pain sensitivity in humans. PMID- 17335977 TI - Heritability of low back pain and the role of disc degeneration. AB - Twin studies suggest that both disc degeneration and back pain have a genetic component. We were interested in estimating the heritability of low back pain in men and examining whether genetic influences on back pain are mediated through genetic influences on disc degeneration. Thus, we conducted a classic twin study with multivariate quantitative genetic models to estimate the degree to which genetic (or environmental) effects on back pain were correlated with genetic (or environmental) effects on disc degeneration. Subjects included 147 monozygotic and 153 dizygotic male twin pairs (N=600 subjects) from the population-based Finnish Twin Cohort. All subjects underwent lumbar magnetic resonance imaging and completed an extensive interview, including back pain history and exposure to suspected risk factors. Disc height narrowing was the degenerative finding most associated with pain history, and was used to index disc degeneration in the models. Statistically significant genetic correlations were found for disc height narrowing and different definitions of back pain, such as duration of the worst back pain episode (r(g)=0.46) and hospitalization for back problems (r(g)=0.49), as well as disability in the previous year from back pain (r(g)=0.33). The heritability estimates for these back pain variables ranged from 30% to 46%. There also were statistically significant, but weaker, environmental correlations for disc height narrowing with back symptoms over the prior year. A substantial minority of the genetic influences on pain was due to the same genetic influences affecting disc degeneration. This suggests that disc degeneration is one pathway through which genes influence back pain. PMID- 17335979 TI - Prevalence and molecular characterization of Cryptosporidium and Giardia species and genotypes in sheep in Maryland. AB - In the United Kingdom and Australia sheep have been implicated as sources of Cryptosporidium and Giardia that infect humans, but no such studies have been conducted in North America. Therefore, a study was undertaken to investigate the prevalence of these parasites in sheep on a farm in Maryland. Feces were collected from 32 pregnant ewes 1, 2, and 3 days after parturition and from each of their lambs 7, 14, and 21 days after birth. The presence of Cryptosporidium oocysts and Giardia cysts was determined by both immunofluorescence microscopy and PCR/gene sequence analysis. PCR was consistently more sensitive than microscopy. The prevalence, by PCR, of Cryptosporidium in ewes and lambs was 25 and 77.4%, respectively. Three species/genotypes of Cryptosporidium were identified: C. parvum, a novel C. bovis-like genotype, and Cryptosporidium cervine genotype. Cryptosporidium parvum and the cervine genotype have been reported worldwide in human infections. The novel C. bovis-like genotype is reported here for the first time. The prevalence of Giardia in ewes and lambs was 12 and 4%, respectively. Most infections were Assemblage E which is not zoonotic; however, one ewe was infected with zoonotic Assemblage A. The identification of only two lambs infected with C. parvum and one ewe infected with G. duodenalis Assemblage A suggests a low prevalence of these zoonoses. However, the high prevalence of the zoonotic cervine genotype indicates that sheep should be considered a potential environmental source of this human pathogen. PMID- 17335980 TI - A 10-year audit of burns at Kalafong Hospital. AB - Kalafong Hospital is a secondary hospital situated to the west of Pretoria. It serves as the regional burns centre for Gauteng province north of the Jukskei river. It mainly serves a poor population. This is a retrospective review of a 10 year period, looking at both numbers and the aetiology of burns treated by this unit. Only adult cases--patients over the age of 12--were assessed. Over this period, a total number of 1046 patients were admitted and treated by this unit, consisting of 634 males and 406 females. The period covered, includes a period when the government has been expending massive amounts of funds to electrify townships and rural areas. Despite this, however, the majority of burn wounds are still caused by open flames and paraffin stoves. PMID- 17335981 TI - Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain. AB - Adenylyl cyclases (ACs) convert ATP to cAMP and therefore, subserve multiple regulatory functions in the nervous system. AC1 and AC8 are the only cyclases stimulated by calcium and calmodulin, making them uniquely poised to regulate neuronal development and neuronal processes such as learning and memory. Here, we detail the production and application of a novel antibody against mouse AC1. Along with AC8 immunohistochemistry, these data reveal distinct and partially overlapping patterns of protein expression in brain during murine development and adulthood. AC1 protein increased in abundance in the neonatal hippocampus from postnatal days 7-14. By adulthood, abundant AC1 protein expression was observed in the mossy fiber tract in the hippocampus and the molecular layer in the cerebellum, with diffuse expression in the cortex and thalamus. AC8 protein levels were abundant during development, with diffuse and increasing expression in the hippocampus that intensified in the CA1/CA2 region by adulthood. AC8 expression was weak in the cerebellum at postnatal day 7 and decreased further by postnatal day 14. Analysis of synaptosome fractions from the adult brain demonstrated robust expression of AC1 in the postsynaptic density and extrasynaptic regions, while expression of AC8 was observed in the presynaptic active zone and extrasynaptic fractions. These findings were confirmed with localization of AC1 and/or AC8 with PSD-95, tau, synaptophysin and microtubule associated protein-2 (MAP-2) expression throughout the brain. Together, these data provide insight into the functional roles of AC1 and AC8 in mice as reflected by their distinct localization in cellular and subcellular compartments. PMID- 17335982 TI - Retention and illicit drug use among methadone patients in Israel: a gender comparison. AB - OBJECTIVES: To examine gender differences or similarities regarding the retention rate in the course of a 13-month treatment and in long-term retention up to 14 years among 2,683 patients treated in eight (of 10) methadone maintenance clinics located in communities in Israel. METHODS: The study is based on a computerized set of data on 2,683 (331 female and 2,352 male) patients older than 18 years of age (mean age=43.30 SD=8.53) who underwent treatment in one of eight methadone maintenance programs in Israel sometimes (or all the time) between January 1, 1991 and October 30, 2005. RESULTS: 79.6% of the patients had a 100% retention rate in the 13-month time slot examined. The survival curves for the long-term retention show that retention in treatment was similar for both female and male patients. However, long-term retention is higher among female patients aged 31 40. CONCLUSION: It is premature to conclude that there are no gender differences in retention since there seem to be different profiles of female patients, characterized by different retention rates, as implied by the great variability in the females' retention behavior found in the regression analysis. PMID- 17335983 TI - Consistency of subjective responses to imagery-induced tobacco craving over multiple sessions. AB - Although studies have demonstrated the validity of imagery procedures to elicit tobacco craving responses in single sessions, few studies have examined the consistency of responding in the same individuals over multiple experimental sessions. In this study, nondeprived smokers were presented with a randomized series of imagery scripts that varied in the intensity of smoking-urge content. At each of five sessions spaced over several weeks, participants were exposed to six imagery trials (two each of no-, low-, and high-intensity imagery scripts). After each trial, participants completed subjective measures of tobacco craving and mood. Ratings of craving and negative mood significantly increased as a function of smoking-urge intensity, which was consistent across the five sessions. Further, significant intraclass correlations indicated that craving and mood responses were highly reliable over the five sessions, as well as across two, three, and four sessions. These results have practical implications for examining individual differences in sensitivity to smoking cues and for studies involving repeated measurement of elicited craving over time. PMID- 17335984 TI - Pioglitazone as a therapeutic agent in autistic spectrum disorder. PMID- 17335985 TI - Mushroom decoctions, a waste product of food processing, may be a potentially valuable source of immunostimulatory and anticancer substances. PMID- 17335986 TI - Anti-metastatic activity of heparin is probably associated with modulation of SDF 1-CXCR4 axis. PMID- 17335987 TI - How could language interact with visuo-spatial performance in autism? PMID- 17335988 TI - Integrating the negative psychotic symptoms in the high risk criteria for the prediction of psychosis. PMID- 17335989 TI - Is a DNA sequence variation of the gene protocadherin Y a possible explanation for the sixfold higher risk to develop schizophrenia in Moroccan males? PMID- 17335990 TI - Activated protein C: therapeutic implications for Alzheimer's disease. PMID- 17335991 TI - Interleukin-6 (IL-6) is still the leading biomarker of the metabolic and aging related disorders. PMID- 17335992 TI - Vitamin E suppresses telomerase activity in ovarian cancer cells. AB - BACKGROUND: Dietary factors influence tumor formation and progression. Vitamin E is a dietary anti-oxidant capable of eliminating free radical damage, inducing apoptosis and decreasing oncogene expression. Therefore, Vitamin E may be a strong candidate for cancer prevention and/or chemotherapeutic intervention. Since telomerase, a ribonucleoprotein uniquely expressed in over 95% of cancers, plays an important role in cellular immortalization, cell growth and tumor progression, the present study investigated the effects of Vitamin E on telomerase activity in human ovarian cancer. METHODS: Normal and malignant ovarian surface epithelial (OSE) cells were cultured with and without D-alpha tocopheryl acetate (Vitamin E). MTS and Western immunoblot assays were used to examine the effect of Vitamin E on cell growth, survival and cytotoxicity. PCR ELISA, RT-PCR and luciferase reporter assays were performed to determine the effect of Vitamin E on telomerase activity. RESULTS: Vitamin E suppressed endogenous telomerase activity in ovarian cancer cells, but had no similar effects in telomerase-negative normal OSE cells. Vitamin E also reduced hTERT mRNA transcript levels and reduced hTERT promoter activity maximally targeting the -976 to -578bp promoter regions. In addition, Vitamin E improved cisplatin mediated cytotoxicity as evidenced by reduced cancer cell growth and increased cleaved caspase 3 activity. In contrast, Vitamin E protected telomerase-negative OSE cells from cisplatin-mediated cytotoxicity as evidenced by decreased cleaved caspase 3 activity. CONCLUSION: Our data suggest that, by suppressing telomerase activity, Vitamin E may be an important protective agent against ovarian cancer cell growth as well as a potentially effective therapeutic adjuvant. PMID- 17335993 TI - 2-aryl benzofurans and their derivatives from seeds of Styrax macranthus. AB - Two new 2-aryl benzofuran derivatives, 3-[7-methoxy-2-(3,4-methylenedioxyphenyl) benzofuran-5-yl]propyl 3-[7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran-5 yl]propanoate (1) and demethoxy egonol gentiobioside (2), were isolated from the aqueous ethanolic extract of the seeds of Styrax macranthus, together with 7 methoxy-2-(3,4-methylenedioxyphenyl)benzofuran-5-carbaldehyde, egonol, demethoxy egonol, demethyl egonol, egonol glucoside, egonol gentiobioside, egonol gentiotrioside, stigmasterol, 2,3-dihydroxypropyl tetracosoate, and daucosterol. Their structures were elucidated on the basis of spectral and chemical evidence. PMID- 17335994 TI - Analgesic activity of methanol extract of Aegle marmelos leaves. AB - The methanol extract of leaves of Aegle marmelos at a dose level of 200 and 300 mg/kg showed significant analgesic activity on acetic acid-induced writhing and tail flick test in mice. PMID- 17335995 TI - Effect of Mitragyna speciosa aqueous extract on ethanol withdrawal symptoms in mice. AB - Administration of the aqueous extract of Mitragyna speciosa at a dose of 300 mg/kg significantly inhibited ethanol withdrawal-induced behaviors that included rearing, displacement and head weaving. The results also showed that at doses of 100, 300 and 500 mg/kg M. speciosa showed antidepressant activity without effect on the spontaneous motor activity. PMID- 17335996 TI - Bioactive plants from Argentina and Bolivia. AB - Antibacterial and molluscicidal activities of methanol and chloroform extracts of 16 plant species belonging to the families Compositae and Melastomataceae were evaluated. The chloroform extract of Vernonanthura tweediana and the methanol extract of Senecio santelisis resulted to be very toxic to brine shrimp nauplii (LC(50)=1 microg/ml). Chloroform extracts of S. santelisis and Senecio leucostachys as well as the methanol extract of Wedelia subvaginata displayed molluscicidal effects on Biomphalaria peregrina showing LC(100)<100 microg/ml. Moderate antibacterial action was produced by the chloroform extracts of Flaveria bidentis, Grindelia scorzonerifolia and Vernonia incana against two strains of Staphylococcus aureus. PMID- 17335997 TI - Antimicrobial and cytotoxic activities of Achyranthes ferruginea. AB - Chloroform extract (CE) of Achyranthes ferruginea and N-trans-feruloyl-4 methyldopamine (1) showed remarkable antimicrobial activities against a wide range of bacteria and fungi. Both crude extract (CE) and compound 1 showed significant cytotoxicity of LC(50) at 16.21 microg/ml and 11.70 microg/ml, respectively. PMID- 17335998 TI - [The fundal height measurements in single pregnancies and the detection of fetal growth retardation]. AB - Symphysis fundus measurements are a reliable mean for screening of fetal growth retardation. The techniques of the measurements, the curves of normality, and the efficiency of this method are discussed. A single formula is put forward to identify the patients witch can profit by extra ultrasound examinations and special clinical surveillance. In France, ultrasound examinations are scheduled at 22 and 32 weeks. Between 22 and 32 weeks, and after 32 weeks, symphysis fundus measurements are needed to suspect intra uterine fetal retardation, and, following suspicion, a new ultrasound examination is helpful. PMID- 17335999 TI - [Comparative evaluation of the Joel-Cohen cesarean section versus the transrectal incision]. AB - OBJECTIVE: The aim of this study was to compare the Joel-Cohen method for cesarean section to the traditional transrectal incision. METHOD: Fifty-two patients requiring a caesarean section were enrolled in this prospective study. Overall morbidity and post-operative pain was assessed. Four surgeons participated to this study, each included 13 patients. The main judgement criterion was post-operative pain on the first day. RESULTS: Post-operative pain on the first day was less important (50 vs 23% p=0.04) in Joel-Cohen's. This method was shorter compared to the transrectal incision (33.6+6.4 min vs 51.2+8 min p<0.0001). There was no difference in overall morbidity between the two groups. CONCLUSION: Joel-Cohen's method decrease post-operative pain and is a shorter procedure compared to the transrectal incision. PMID- 17336000 TI - Experimental functional response and inter-individual variation in foraging rate of teal (Anas crecca). AB - The functional response, i.e. the change in per capita food intake rate per time unit with changed food availability, is a widely used tool for understanding the ecology and behaviour of animals. However, waterfowl remain poorly explored in this context. In an aviary experiment we derived a functional response curve for teal (Anas crecca) foraging on rice (Oryza sativa) seeds. We found a linear relationship between intake rate and seed density, as expected for a filter feeder. At high seed densities we found a threshold, above which intake rate still increased linearly but with a lower slope, possibly reflecting a switch from filter-feeding to a scooping foraging mode. The present study shows that food intake rate in teal is linearly related to food availability within the range of naturally occurring seed densities, a finding with major implications for management and conservation of wetland habitats. PMID- 17336001 TI - First serological and molecular evidence on the endemicity of Anaplasma ovis and A. marginale in Hungary. AB - Recurring and spontaneously curing spring haemoglobinuria was recently reported in a small sheep flock in a selenium deficient area of northern Hungary. In blood smears of two animals showing clinical signs, Anaplasma-like inclusion bodies were seen in erythrocytes. To extend the scope of the study, 156 sheep from 5 flocks and 26 cattle from 9 farms in the region were examined serologically with a competitive ELISA to detect antibodies to Anaplasma marginale, A. centrale and A. ovis. The seropositivity in sheep was 99.4%, and in cattle 80.8%. A. ovis and A. marginale were identified by PCR and sequence analysis of the major surface protein (msp) 4 gene in sheep and cattle, respectively. Haemoglobinuria, an unusual clinical sign for anaplasmosis might have been a consequence of transient intravascular haemolysis facilitated by selenium deficiency in recently infected sheep, as indicated by the reduction of mean corpuscular haemoglobin concentration (MCHC). Membrane damage was also demonstrated for parenchymal cells, since their enzymes showed pronounced elevation in the plasma. Ticks collected from animals in the affected as well as in neighbouring flocks revealed the presence of Dermacentor marginatus, Ixodes ricinus and D. reticulatus, with the dominance of the first. The present data extend the northern latitude in the geographical occurrence of ovine anaplasmosis in Europe and reveal the endemicity of A. ovis and A. marginale in Hungary. PMID- 17336002 TI - Postnatal maternal cortisol levels predict temperament in healthy breastfed infants. AB - BACKGROUND: The implications of the biologically active elements in breast milk for the breastfed infant are largely unknown. Animal models suggest that ingestion of glucocorticoids during the neonatal period influences fear behavior and modifies brain development. AIMS: To determine the association between postnatal maternal cortisol levels and temperament in breastfed infants. STUDY DESIGN: The relation between maternal cortisol and infant temperament was examined in breastfed and formula-fed infants. Plasma cortisol was used as a surrogate measure for breast milk cortisol levels (plasma and milk levels are correlated in the 0.6 to 0.7 range; [Patacchioli FR, Cigliana G, Cilumbriello A, Perrone G, Capri O, Alema GS, et al. Maternal plasma and milk free cortisol during the first 3 days of breast-feeding following spontaneous delivery or elective cesarean section. Gynecologic and Obstetric Investigations 1992;34:159 163.]. If exposure to elevated cortisol levels during infancy influences temperament, then a relation between the two should be found among the breastfed infants, but not among the formula-fed infants. SUBJECTS: Two hundred fifty-three two-month-old infants and their mothers. OUTCOME MEASURES: Fearful temperament assessed with the Infant Behavior Questionnaire [Garstein MR, Rothbart MK. Studying infant temperament via the revised infant behavior questionnaire. Infant Behavior and Development 2003;26:64-86]. RESULTS: Among the breastfed infants, higher maternal cortisol levels were associated with reports of increased infant fear behavior (partial r=0.2; p<0.01). This relation did not exist among the formula-fed infants. Negative maternal affect at the time of assessment did not account for the positive association in the breastfed group. CONCLUSIONS: The findings are consistent with our proposal that exposure to cortisol in breast milk influences infant temperament. Biologically active components in breast milk may represent one avenue through which the mother shapes the development of the human infant during the postnatal period. PMID- 17336003 TI - Refined PBPK model of aggregate exposure to methyl tertiary-butyl ether. AB - Aggregate (multiple pathway) exposures to methyl tertiary-butyl ether (MTBE) in air and water occur via dermal, inhalation, and oral routes. Previously, physiologically based pharmacokinetic (PBPK) models have been used to quantify the kinetic behavior of MTBE and its primary metabolite, tertiary-butyl alcohol (TBA), from inhalation exposures. However, the contribution of dermal and oral exposures to the internal dose of MTBE and TBA were not characterized well. The objective of this study was to develop a multi-route PBPK model of MTBE and TBA in humans. The model was based entirely on blood MTBE and TBA measurements from controlled human exposures. The PBPK model consists of nine primary compartments representing the lungs, skin, fat, kidney, stomach, intestine, liver, rapidly perfused tissue, and slowly perfused tissue. The MTBE and TBA models are linked by a single metabolic pathway. Although the general structure of the model is similar to previously published models of volatile organic compounds, we have now developed a detailed mathematical description of the lung, skin, and gastrointestinal tract. This PBPK model represents the most comprehensive and accurate description of MTBE and TBA pharmacokinetics in humans to date. The aggregate exposure model application for MTBE can be generalized to other environmental chemicals under this framework given appropriate empirical measurement data. PMID- 17336004 TI - Routine screening mammography in women older than 74 years: a review of the available data. AB - OBJECTIVE: The efficacy of population screening mammography for the age group of 50-74 years has been demonstrated. However, only limited data are available regarding women aged 75 and over, and recommendations for breast cancer screening in this age group vary in different countries. The aim of the current study is to review the evidence of the efficacy of breast cancer screening in women over the age of 74 years. METHODS: Studies published in English were retrieved by systematically searching MEDLINE (for papers published until August 2006), and by manually examining the references of the original articles and reviews retrieved. All studies that dealt with screening mammography over age 74 years were included. The studies were reviewed according to their outcomes and study design, focusing on breast cancer mortality and stage of breast cancer at diagnosis. RESULTS: Three studies focused on the relationship between breast cancer screening and mortality; in the 75-84 years age group, the risk of disease specific mortality was approximately two-fold higher among women who did not perform screening mammography compared to women who did. Another four studies showed that women who underwent screening mammography had significantly smaller tumors and earlier disease stage at diagnosis. CONCLUSIONS: Regular mammography screening in older women may be associated with an earlier-stage disease and lower breast cancer mortality. These data support the use of screening mammography above age 75 years based on individual evaluations, rather than setting an upper age limit for breast cancer screening. PMID- 17336005 TI - Stabilization of recombinant human growth hormone against emulsification-induced aggregation by Pluronic surfactants during microencapsulation. AB - Protein aggregation upon exposing to the water/organic solvent interface is one of the most significant obstacles in developing poly(lactic-co-glycolic acid) (PLGA) microspheres with double emulsion process. The aim of present study is to devise a formulation strategy to prevent recombinant human growth hormone (rhGH) from aggregation during microencapsulation. The excipients used for stabilizing rhGH were selected from sugars, nonionic surfactants, polyol, and protein. Among the candidates, surfactants exhibited potentialities in protecting rhGH against emulsification-induced aggregation. It was also found that Pluronic F127 showed an outstanding as well as concentration-dependent stabilizing effect on rhGH, which was different to Pluronic F68 and Tween 20. After the rhGH solution comprising F127 and sucrose was emulsified with methylene chloride, the recovery of monomeric protein achieved 99.0%, principally attributed to the presence of F127. This solution was subsequently encapsulated as inner aqueous phase in the PLGA microspheres by a conventional double emulsion process, with the encapsulation efficiency higher than 98%. Improvement in the release of rhGH was observed for the microspheres co-encapsulating Pluronic F127 regardless in the presence or absence of sucrose, compared to the microspheres containing rhGH alone. The result further implied that co-encapsulation of Pluronic F127 in the microspheres played an important role in the stabilization of rhGH. PMID- 17336006 TI - Plasma membrane Ca2+-ATPase isoforms in frog crista ampullaris: identification of PMCA1 and PMCA2 specific splice variants. AB - Ca2+ ions play a pivotal role in inner ear hair cells as they are involved from the mechano-electrical transduction to the transmitter release. Most of the Ca2+ that enters into hair cells via mechano-transduction and voltage-gated channels is extruded by the plasma membrane Ca2+-ATPases (PMCAs) that operate in both apical and basal cellular compartments. Here, we determined the identity and distribution of PMCA isoforms in frog crista ampullaris: we showed that PMCA1, PMCA2 and PMCA3 are expressed, while PMCA4 appears to be negligible. We also identify PMCA1bx, PMCA2av and PMCA2bv as the major splice variants produced from PMCA1 and PMCA2 genes. PMCA2av appears to be the major Ca2+-pump operating at the apical pole of the cell, even if PMCA1b is also expressed in the stereocilia. PMCA1bx is, instead, the principal PMCA of hair cell basolateral compartment, where it is expressed together with PMCA2 (probably PMCA2bv) and PMCA3. Frog crista ampullaris hair cells lack a Na/Ca exchanger, therefore PMCAs are the only mechanism of Ca2+ extrusion. The coexpression of specific isozymes in the different cellular compartments responds to the need of a fine regulation of both basal and dynamic Ca2+ levels at the apical and basal pole of the cell. PMID- 17336007 TI - Experimental diabetes treated with Achillea santolina: effect on pancreatic oxidative parameters. AB - Oxidative stress is produced under diabetic condition and is likely involved in progression of pancreatic damage found in diabetes. In the present study, we examined possible protective effect of Achillea santolina L. (Compositae) against pancreatic damage in streptozotocin (STZ)-treated diabetic rats. Achillea santolina extract (ASE) is used by the traditional healers in many part of Iraq, as a hypoglycaemic agent. We evaluated the effect of ASE on blood glucose level, serum nitric oxide (NO) concentration and the oxidative stress status in rat pancreatic tissue. STZ was injected intraperitonealy at a single dose of 40mgkg( 1) to induce diabetes. ASE (0.1g/kgday) was orally administered to a group of diabetic rats for 30 consecutive days. Results showed significant reduction in the activities of superoxide dismutase (SOD), catalase (CAT) and pancreatic glutathione (GSH) levels in the diabetic rats compared to the control subjects. On the other hand, blood glucose level, serum NO, malondialdehyde (MDA), a marker of lipid peroxidation, protein oxidation indices including protein carbonyl (PCO) and advanced oxidation protein products (AOPP) were significantly elevated in pancreas of the diabetic group. Treatment with ASE reduced blood glucose level, serum NO, pancreatic MDA, PCO and AOPP. In addition, the content of GSH was restored to the normal level of the control group. Furthermore, ASE significantly increased CAT and SOD activities in ASE-treated rats. Based on our data, it can be concluded that Achillea santolina have a high hypoglycaemic activity and this may be attributed to its antioxidative potential. PMID- 17336008 TI - Post-mortem forensic neuroimaging: correlation of MSCT and MRI findings with autopsy results. AB - Multislice-computed tomography (MSCT) and magnetic resonance imaging (MRI) are increasingly used for forensic purposes. Based on broad experience in clinical neuroimaging, post-mortem MSCT and MRI were performed in 57 forensic cases with the goal to evaluate the radiological methods concerning their usability for forensic head and brain examination. An experienced clinical radiologist evaluated the imaging data. The results were compared to the autopsy findings that served as the gold standard with regard to common forensic neurotrauma findings such as skull fractures, soft tissue lesions of the scalp, various forms of intracranial hemorrhage or signs of increased brain pressure. The sensitivity of the imaging methods ranged from 100% (e.g., heat-induced alterations, intracranial gas) to zero (e.g., mediobasal impression marks as a sign of increased brain pressure, plaques jaunes). The agreement between MRI and CT was 69%. The radiological methods prevalently failed in the detection of lesions smaller than 3mm of size, whereas they were generally satisfactory concerning the evaluation of intracranial hemorrhage. Due to its advanced 2D and 3D post processing possibilities, CT in particular possessed certain advantages in comparison with autopsy with regard to forensic reconstruction. MRI showed forensically relevant findings not seen during autopsy in several cases. The partly limited sensitivity of imaging that was observed in this retrospective study was based on several factors: besides general technical limitations it became apparent that clinical radiologists require a sound basic forensic background in order to detect specific signs. Focused teaching sessions will be essential to improve the outcome in future examinations. On the other hand, the autopsy protocols should be further standardized to allow an exact comparison of imaging and autopsy data. In consideration of these facts, MRI and CT have the power to play an important role in future forensic neuropathological examination. PMID- 17336009 TI - Autonomic responses during motion sickness induced by virtual reality. AB - OBJECTIVE: To examine the development of subjective symptoms and heart rate variability (HRV) during motion sickness induced by virtual reality (VR). METHODS: Subjects were 10 healthy young volunteers. During VR immersion, subjects were immersed in a visual-vestibular conflict produced by VR. The levels of the subjective symptoms were assessed by Graybiel's and Hamilton's criteria. HRV was determined by measuring microvascular blood flow or electrocardiogram. RESULTS: Subjective symptoms evaluated by Graybiel's and Hamilton's criteria were gradually worsened during VR. Power spectrum analysis of HRV demonstrated a gradual increase in the low frequency but no change in the high frequency during VR. In this study, individual subjective symptoms were not correlated with the individual result of power spectrum analysis. CONCLUSION: These findings indicate that there was an increase in sympathetic nervous activity, but no change in parasympathetic nervous activity during motion sickness induced by VR. Given the large inter-individual variability and the reliability of subjective measures, it is not surprising that there is scarcely a relation between the subjective symptoms and the results of power spectrum analysis. PMID- 17336010 TI - Congenital ocular motor apraxia: clinical and neuroradiological findings, and long-term intellectual prognosis. AB - The severity of intellectual sequelae and prognosis varies in patients with congenital ocular motor apraxia (COMA). Here, we explored this phenomenon with regard to the accompanying oculomotor signs and gross motor development, as well as the subtentorial structure defects. Ten patients diagnosed with COMA (M:F=4:6, 4-37 years old) were reviewed. Four individuals who gained the ability to walk at 2 years or earlier showed normal intellect and social skills. Those who walked later often showed accompanying intellectual (5/6) and speech (6/6) disabilities. In this latter group, atypical oculomotor signs for COMA (presence of nystagmus, mild limitation of vertical gaze, slower head thrust, and marked improvement of lateral saccade during early childhood) were often noted (4/6). Minor anomalies of fingers and toes were also common in this group. Neuroimaging was conduced in nine patients (pneumoencepharography 1; computed tomography: 8, magnetic resonance imaging: 2). Dilatation of the fourth ventricle, mainly at the level of the midbrain or upper pons (n=7), and hypoplastic cerebellar vermis (n=6) were commonly observed in both the early- and late-walking groups. 'Molar tooth' signs (n=3) were exclusively noted in the late-walking group, and often accompanied by atypical oculomotor signs (3/3) and intellectual disabilities (2/3). Vermian hypoplasia and dilatation of the fourth ventricle at the upper brainstem level in COMA patients, with or without intellectual disabilities, suggested that the cardinal lesion for OMA may exist in these areas. The presence of a subset of 'atypical' COMA patients may suggest that COMA with subtle infratentorial abnormality represents a heterogeneous disease category, showing similar oculomotor disturbance. This review indicated that clinical and neuroradiological inspection might be valuable for prediction of long-term intellectual prognosis in COMA patients. PMID- 17336011 TI - [Adverse effects of antitubercular drugs: epidemiology, mechanisms, and patient management]. AB - Tuberculosis, what ever its localization, is an infectious disease which can be totally cured by combining antitubercular drugs. Current therapeutic regimens with isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin have proved successful in treating tuberculosis. However, they are associated to a high rate of adverse effects that can lead to therapeutic failure. Understanding the nature and the severity of these adverse effects allows for their appropriate management. Toxic neuropathy and hepatitis are the most common adverse reactions to isoniazid. Rifampicin is generally well tolerated but some severe immuno allergic reactions may occur in case of intermittent regimen. Pyrazinamide induced liver injury is rare but sometimes lethal. Joint affections, usually due to hyperuricemia, are more frequent but easily manageable. The major adverse effect related to ethambutol is ocular optic neuropathy. It occurs dose dependently and can be irreversible. Finally, administration of streptomycin is potentially associated with renal and cochleo-vestibular toxicity that might be milder than when induced by other aminoglycosides. The management of antituberculosis-induced adverse effects depends on parameters related to the adverse effect itself and to the administrated drug. PMID- 17336012 TI - [Spondylodiscitis due to Moraxella lacunata]. AB - Infectious spondylodiscitis is an uncommon disease, often diagnosed late. The main pathogen is Staphylococcus aureus. We report a case of spondylodiscitis diagnosed early, caused by Moraxella lacunata, a Gram-negative bacillus of usually low pathogenicity for man. A combination of amoxicillin 12 g/day IV then per os, and ciprofloxacine 1,500 mg/day per os was given for 8 weeks. Evolution was favorable. PMID- 17336013 TI - Amino acid and codon use: in two influenza viruses and three hosts. AB - OBJECTIVE: The aim of this study was to compare the use of amino acids and codons in influenza viruses A and B and in their common hosts, to highlight any relevant difference. METHODS: The frequency of the 20 amino acids and of the 61 codons was studied in influenza viruses A, B, and in man, pig, and chicken. The correlation in amino acid and codon use among these hosts was calculated. RESULTS: The correlation between the frequency of the 20 amino acids and the molecular weight was also calculated and it was very similar in all studied hosts, ranging from 0.506 to 0.595. The correlation of codon frequency among these organisms was highest between man and chicken (r=0.974), and lowest between pig and virus B (r=0.147). CONCLUSIONS: The important correlation in codon use among the three hosts and the two viruses suggests there was a remote lateral gene transfer among the three hosts and the two viruses. The higher use of alanine, leucine, and proline in man versus virus A is significant. PMID- 17336014 TI - Emergence of vancomycin-resistant Enterococcus faecium in Sfax: clinical features and molecular typing. PMID- 17336015 TI - [Streptococcus pneumoniae cellulitis in a diabetic patient]. AB - Pneumococcal cellulitis is an uncommon infection. Head, neck, and trunk are usually affected in patients with hematological malignancies and lupus erythematosus. Limb cellulitis is frequently observed in patients with diabetes mellitus, drug abusers, or alcoholics. Patients present with septic shock most of the time. Surgical treatment is necessary in 50% of the cases. The outcome is usually favorable. We describe the case of a 72-year-old alcoholic patient with diabetes mellitus presenting with cellulitis and septic shock. Serotype 19 Streptococcus pneumoniae with abnormal susceptibility to penicillin (MIC: 0.75 mg/l) was isolated from cellulitis and in blood culture. The evolution was favorable after itavenous antibiotherapy combining ceftriaxone(DCI) (2 g/j), metronidazole(DCI) (1 g/j), and ciprofloxacin(DCI). PMID- 17336016 TI - [Lactococcus lactis: an opportunistic bacterium?]. AB - Lactic bacteria have been used for centuries to ferment food and thus, to better preserve them. Considered as inoffensive for man, its use has largely spread in food industry. Some species are even being considered for the treatment of human diseases. Indeed, the development of new cellular biology technologies opens opportunities for the use of these bacteria as biotherapeutic agents. These species would produce heterogeneous proteins such as enzymes (lipase, lactase, esterase), chemical mediators (hormones and interleukins), and molecules able to stimulate local immune responses. However, rare cases of human infection, sometimes severe, were reported recently. They generally occured in patients with comorbidities with consumption of unpasteurized dairy products reported for some. The scarcity of these cases and their favorable outcome should not hinder the industrial and medical use of these bacteria. PMID- 17336017 TI - [Disseminated aspergillosis after intra-articular corticosteroid infiltrations]. AB - Bone and joint infections due to Aspergillus are rare and occur more commonly in immunosuppressed patients. We report the case of an 84-year-old woman who developed septic arthritis caused by Aspergillus fumigatus after corticosteroid infiltration. This patient had presented with arthritis of the left knee for several months but no microorganism had been found despite numerous arthrocenteses. This arthritis was resistant to treatment by numerous corticosteroid infiltrations. During an arthroscopy, analysis of the synovial fluid yielded A. fumigatus. Thereafter, other explorations showed disseminated aspergillosis with osteo-articular destruction, blood and urinary dissemination. A systemic treatment by voriconazole associated to intra-articular injections and surgical debridement was initiated but the patient died. Septic arthritis caused by A. fumigatus is very rare but must be considered as a differential diagnosis of septic arthritis after corticosteroid infiltration. Their complications can be very important and destructive. PMID- 17336018 TI - [A new case of acute transverse myelitis following hepatitis A virus infection]. AB - Transverse myelitis is a rare manifestation of hepatitis A virus infection. We report the case of an eleven-year-old girl who presented a progressive flabby paraplegia with sphincter incontinence, superficial hypoesthesia, without deep involvement. Medullar MRI was suggestive of myelitis. Despite the absence of jaundice and hepatic cytolysis, the serology yielded a high rate of anti hepatitis A immunoglobulin M. Neurological disorders disappeared within 15 days, after treating with a high dose of corticosteroids and physical rehabilitation. 24 months later she was asymptomatic. Screening for hepatitis A virus infection in patients with acute transverse myelitis should be indicated specially in endemic countries were vaccinal prophylaxis is not common practice. PMID- 17336019 TI - [Relationship between antibiotic policies and antibiotic consumption in hospitals]. AB - OBJECTIVE: The authors had for aim to study the relationship between antibiotic policies and antibiotic consumption in hospitals. DESIGN: A component analysis was used to summarize the various measures of the antibiotic policies developed by hospitals. Antibiotics consumption was expressed as a number of Daily Defined Doses per 1,000 patient-days. The relation was studied by a multiple linear regression model with adjustment on hospital activity. RESULTS: The first component illustrated an active program of antibiotic policies associating: a local antibiotic committee, an infectious diseases consultant, written local guidelines for prescriptions and restrictive measures before dispensing. The highest antibiotic consumption was associated with active policies, especially for carbapenems, glycopeptides, and aminoglycosides. However the relationship differed according to the type of hospital, with lower antibiotic consumption, especially for penicillins, in private hospitals that had more active policies. CONCLUSION: The difference between public and private hospitals could be explained by the type of institution but also by the unit used to measure antibiotic consumption. PMID- 17336020 TI - [Infections due to Group B Streptococci in the Casablanca Ibn-Rochd university hospital between 2003 and 2005]. PMID- 17336021 TI - [Vaccination status of Burgundy inhabitants: a survey in various institutions]. AB - AIM: The authors had for aim to determine the vaccination coverage in Burgundy. This study was based on data collection from institutions either in charge of vaccination or controlling the vaccination coverage of given target populations. METHOD: The concerned institutions were asked to provide a representative sample of the population controlled between September 2000 and June 2001 and a longitudinal study was carried out on the data. The analysis of vaccination coverage was made by institution and included i) the rate of people carrying a document proving their vaccination, ii) the rate of minimal vaccination coverage, and iii) the rate of maximal vaccination coverage. RESULTS: 4,159 people participated in the study. The analysis revealed that, on the first university medical follow-up, young people rarely carried a vaccination certificate. This rate increased in occupational medicine and in healthcare institutions. The minimum rates of vaccination coverage against tetanus strongly decreased for population of over 60 years of age (39.6%), and adults living in precariousness (44.3%). In occupational medicine, 34.2% of women ignored their vaccinal status against rubella, almost 10% said that they had not contracted the disease and were not vaccinated. CONCLUSION: This survey confirmed the urgent need to improve the vaccination coverage against tetanus for people over 60 years of age, and vaccination against rubella for women of reproductive age. It also demonstrated the need to provide adults with an appropriate vaccination file allowing recording and saving their respective vaccination status. PMID- 17336022 TI - Study on the compatibility of cefotaxime with tinidazole in glucose injection. AB - An efficient HPLC method for the compatibility study of cefotaxime with tinidazole in glucose injection is described, which has been developed for the simultaneous determination of cefotaxime and tinidazole in glucose injection. The appearance and pH value of the mixed solution were investigated and the concentrations of cefotaxime and tinidazole were determined by RP-HPLC with an Agilent ZORBAX Eclipse XDB-C8 column, gradient elution and dual wavelength detection on diode-array-detector (DAD) at room temperature (20 degrees C) within 24 h. It was found that the resulting appearance and pH value of the mixed solution showed slight changes, on the other hand, the quantity of cefotaxime decreased significantly. The results show that the mixed solution of cefotaxime with tinidazole in glucose injection must be used within 8 h in clinical due to the possible degradation of cefotaxime in tinidazole glucose injection. This study provides a convenient method for rational use of compatible drugs in clinical practice. PMID- 17336023 TI - Thermodynamic properties of flufenamic and niflumic acids--specific and non specific interactions in solution and in crystal lattices, mechanism of solvation, partitioning and distribution. AB - Temperature dependency of saturated vapour pressure and the thermochemical characteristics of the fusion process were measured for flufenamic acid and niflumic acid, and thermodynamic functions of sublimation, fusion and evaporation calculated. An approach to split specific and non-specific energetic terms in crystal lattices is developed. The melting points of the considered molecules correlate with the ratio between specific and non-specific interactions in crystal lattices. Temperature dependencies of the solubility in buffers with pH 2.0 and 7.4, in n-octanol and in n-hexane were measured. The thermodynamic functions of solubility, solvation and transfer processes were deduced. Specific and non-specific solvation terms were distinguished by the transfer from "inert"n hexane to the other solvents. Comparison of the ratio between specific and non specific interactions in solid state and in the solutions was carried out. A diagram to analyse energetic terms of partitioning and distribution processes is introduced. PMID- 17336024 TI - Physicochemical profile of nimesulide. Exploring the interplay of lipophilicity, solubility and ionization. AB - The lipophilicity and solubility profile of nimesulide was investigated over a broad pH range. Lipophilicity was assessed by direct partitioning experiments in the octanol-water system using the shake flask method, as well as by reversed phase HPLC using methanol as organic modifier with or without addition of n octanol. In the latter case the extrapolated retention factors logk(w) were considered as lipophilicity indices. The presence of n-octanol in the mobile phase proved to be a crucial factor for the establishment of a logk(w)/pH profile very similar to the logD/pH profile of nimesulide. Solubility was determined by the shake flask method using saturated buffer solutions. Both lipophilicity and solubility--pH profiles of nimesulide showed deviations from the theoretically expected behavior as dictated by the Henderson-Hasselbach equation and the usually recorded difference of 4 log units between the corresponding values of the neutral and ionized species in the case of a weak acid. As a consequence the lipophilicity and solubility profiles were found not to be mirror images of each other. However, the pK(a) value of nimesulide could be accurately calculated using part of both lipophilicity and solubility profiles since deviations affected mostly the values at increased ionization. PMID- 17336025 TI - Feasibility and induced cognitive-emotional change of an emotional disclosure intervention adapted for home application. AB - OBJECTIVE: Emotional engagement, cognitive restructuring, and positive future directedness are considered core elements to induce change in emotional disclosure interventions. Our aim was to examine the induction of these elements and the feasibility of an emotional disclosure intervention adapted for home application. METHODS: The intervention emphasized expression of negative and positive emotions (session 1-4), search for meaning (session 3), and a positive future-oriented ending (session 4). A randomized clinical trial in patients with rheumatoid arthritis compared the adapted intervention (n=40) with a time management control condition (n=28). Feasibility was evaluated regarding adherence, compliance with instructions, perceived viability, and clinical safety. Induction of core elements was evaluated by analysis of change in immediate affective responses and by computerized text analysis of word use. RESULTS: Feasibility criteria were successfully met. The disclosure condition produced higher immediate negative affect and use of emotion, insight, and optimism words compared to control, and induced the elements of change within sessions as intended. CONCLUSION: The adapted intervention is feasible for home application and induces change in variables that indicate emotional engagement, cognitive restructuring, and positive future directedness. PRACTICE IMPLICATIONS: Empirical support of health benefits of this emotional disclosure intervention will extend its applicability in patient self-care. PMID- 17336026 TI - Interactive voice response telephony to promote smoking cessation in patients with heart disease: a pilot study. AB - OBJECTIVE: A pilot study was conducted to determine the feasibility and potential efficacy of an interactive voice response (IVR) follow-up system for smokers recently hospitalized with coronary heart disease (CHD). METHODS: Ninety-nine smokers hospitalized with CHD completed a baseline questionnaire, were provided with bedside counseling, and offered nicotine replacement therapy. They were randomly assigned to a usual care (UC) or an IVR group. The IVR group received automated telephone follow-up calls 3, 14 and 30 days after discharge inquiring about their smoking status and confidence in remaining smoke-free. When deemed necessary, they were offered additional counseling. Smoking status was determined 52 weeks after hospital discharge. RESULTS: The 52-week point prevalence abstinence rate in the IVR group was 46.0% compared to 34.7% in the UC group (OR=1.60, 95% CI: 0.71-3.60; P=.25). After adjustment for education, age, reason for hospitalization, length of hospitalization, and quit attempts in the past year, the odds of quitting in the IVR group compared to the UC group were 2.34 (95% CI: 0.92-5.92; P=.07). CONCLUSIONS: IVR is a promising technology for following CHD patients attempting to quit smoking following discharge from hospital, however, a larger trial is required to confirm its efficacy. PRACTICE IMPLICATIONS: IVR may enhance the timely provision of follow-up counseling for smoking cessation in patients with CHD. PMID- 17336027 TI - Changing hats: from doctor to patient. PMID- 17336028 TI - Treatment of lycorine on SCID mice model with human APL cells. AB - In our previous study, lycorine, a natural alkaloid extracted from Amaryllidaceae, exhibited anti-leukemia effects in vitro. To determine whether lycorine has an anti-tumor effect in vivo, a series of experiments were carried out in this study. HL-60 cells (5 x 10(6)) were inoculated i.v. into severe combined immuno-deficiency (SCID) mice after these mice had been irradiated (total body receiving 200cGy chi irradiation). Treatment was given once a day from day 2 to 6, and from day 14 to 18. Lycorine (5 or 10 mg/kg/day i.p.) was found to decrease the percentages of immature granular leukocytes and of monocytes among the peripheral blood cells, and the mean survival time of both lycorine-treated groups was longer than that of the control group. Compared with the asynchronous and cytosine arabinoside- (Ara-C) treated (20 mg/kg/day i.p.) group, treatment with lycorine was more effective. Lycorine was also found to alleviate the infiltration of tumor cells into the liver, bone, and marrow. When SCID mice inoculated with HL-60 cells were then treated with lycorine, no severe adverse effects were observed. This study revealed that lycorine, when tested in the human leukemia xenograft models, appears to exhibit anti-tumor activity in vivo and is a useful therapy against acute promyelocytic leukemia. PMID- 17336029 TI - Effect of aspirin on DNA damage induced by MMC in Drosophila. AB - In our previous paper, we found that aspirin suppressed the genotoxicity of mitomycin C (MMC) in a somatic mutation and recombination test (SMART) in Drosophila melanogaster. In order to reveal the mechanism of antigenotoxicity of aspirin, we evaluated the protective effects of aspirin against the genotoxicity of MMC with the DNA repair test in Drosophila melanogaster. Three types of treatment of aspirin were performed as co-, post- and pre-treatment. Aspirin co treatment suppressed effectively the genotoxicity of MMC in a dose-dependent manner and the sex ratio at a dose of aspirin 10mg/bottle elevated from 0.01 (without aspirin) to 0.65 at sc z(1) w(+(TE)) mei-9(a) mei-41(D5)/-C(1)DX, y f [mei-9 mei-41, Rec(-) male.Rec(+) female] consists of DNA repair-deficient (Rec( )) males and -proficient (Rec(+)) females. The antigenotoxic effect of aspirin on [mei-41, Rec(-) male.Rec(+) female] was similar to that on [mei-9, Rec(-) male.Rec(+) female]. But post- and pre-treatment by aspirin did not affect the genotoxicity of MMC on [mei-9 mei-41, Rec(-) male.Rec(+) female]. PMID- 17336030 TI - [Parasitic diarrhea]. AB - After a trip to tropical areas, diarrhea is frequent and is most often due to a parasite. Amebiasis is the principal cause of acute diarrhea. The other intestinal parasites cause chronic diarrhea, including in temperate countries; these include Giardia, Cryptosporidium, and Microsporidium species in immunocompromised patients. Helminthic diseases, either cosmopolitan (Ascaris, Enterobius, and Taenia) or tropical (hookworms, Strongyloides, and Schistosoma), cause diarrhea with blood hypereosinophilia. Diagnosis is based on the examination of stool. Treatment is rapid, effective and well tolerated, while prophylaxis is often difficult to explain to the populations concerned. PMID- 17336031 TI - [Cholera]. AB - Cholera is an acute intestinal infection that has reached pandemic proportions and presents a major international health concern. Every year, more than 100000 cholera cases and 2000-3000 deaths are officially reported to WHO. The real figures for cholera are thought to be much higher, however, due to underreporting and other limitations of surveillance systems. Cholera is caused by two serogroups (O1 and O139) of a gram-negative bacterium, Vibrio cholerae. Cholera toxins cause a massive outpouring of electrolyte-rich isotonic fluid into the bowel and can lead to volume depletion and shock. In poor sanitary and individual hygiene conditions, the massive release of cholera vibrios into the environment intensifies and exacerbates cholera epidemics, which thus serve as clear markers of poverty and lack of basic sanitation. Rehydration therapy, either intravenous or oral, considerably decreases the number of deaths. The WHO recommends antibiotics for cholera cases with severe dehydration. If left untreated, cholera has a 25-50% mortality rate. Treatment reduces this to less than 1%. Bacteriological diagnosis of cholera is reasonably easy because cholera bacteria are abundant in stool. Epidemics, however, often occur in areas with either limited or no laboratory facilities. A rapid and accurate diagnosis of cholera is essential to mobilize resources for treatment and containment of the epidemic. Therefore, the Pasteur Institute has developed a rapid diagnostic test based on a one-step immunochromatographic technique, which should be commercially available soon. To date, two oral cholera vaccines have been shown to offer good (more than 70%) short-term (one year) protection. WHO recommends these vaccines as an additional public health tool to be implemented with the standard cholera control measures, including provision of safe drinking water and adequate sanitation. Nonetheless, a cholera vaccine that can offer a long-term protection for all age groups, including children younger than five years, is still needed. PMID- 17336032 TI - [Tropical diarrheas: consequences of poverty]. PMID- 17336033 TI - [Tropical sprue]. AB - Tropical sprue associates prolonged diarrhea, a malabsorption syndrome, and nutritional deficiency in patients who live in or have visited tropical areas. Pathogenesis is still unknown but an infectious cause is suspected. Macrocytic anemia and hypoalbuminemia are present, together with progressive villus atrophy of the small intestine. Treatment with tetracycline, folic acid and proper nutritional support generally results in full recovery. PMID- 17336034 TI - Neuropsychological impairment after hemorrhagic stroke in basal ganglia. AB - We aimed to determine the severity and pattern of cognitive dysfunction in patients with basal ganglia (BG) hemorrhage within the first 6 months after stroke and to identify its clinical correlates. The study samples consisted of 30 patients with BG hemorrhage and 37 healthy controls. A comprehensive neuropsychological battery including tests of attention, memory, language, visuospatial function, and executive function was administered to all participants. Relative to healthy controls, BG patients performed significantly worse across different cognitive domains after controlling for age, sex, and education. 96.7% of patients displayed defective performance on at least three neuropsychological tests. Discriminant function analysis showed that visuospatial function and memory were the best predictors of group membership (patient/control), with an overall classification rate of 95.5%. Only side of stroke and admission Glasgow Coma Scale (GCS) score correlated significantly with some of the cognitive domains. The widespread pattern of cognitive deficits seen in BG patients provides evidence for the substantial involvement of the BG in many neuronal pathways connecting cortical and subcortical brain areas responsible for various cognitive functions. PMID- 17336035 TI - Executive functioning in healthy elderly Chinese people. AB - This study aimed to explore the executive function of healthy elderly Chinese people. A sample of 58 healthy Chinese aged 60 and over was recruited from Guangzhou in China. They were divided into two age groups, a younger age group (aged 60-70) and an older age group (aged over 70). Executive function was measured by a battery of seven tests which were assumed to capture specific components of executive function. The tests were initiation (Hayling Sentence Completion Test (HSC)), sustained attention (Monotone Counting Test), switching and flexibility (word fluency and modified Wisconsin Card Sorting Test (WCST)), disinhibition (Modified Six Element Task (SET), Stroop Test, and HSC), attention allocation and planning (SET and modified version of WCST), and updating (Chinese Letter-Number Span). When independent neurocognitive tests were analyzed, there were significant age differences in the WCST (perseverative errors and category completed, p=0.025, 0.023) and the SET (raw score, p=0.050). The older age group tended to do worse in the total profile score of the SET and correct responses of the HSC Part A. However, when these tests were grouped into specific executive function components, a significant difference was found between the two groups in attention allocation and planning (p=0.007) and total component score (p=0.026). Regression analyses also indicated that age accounted for only very little variance of executive function in this narrow band of the elderly, whereas educational level accounted for a large part of the variance in initiation (R(2)=0.252, p<0.001), switching and flexibility (R(2)=0.211, p<0.001), and updating (R(2)=0.236, p<0.001) components of executive function. Our findings suggest that a significant decline in general executive functioning with advancing age was only evident in some putative tests in this sample. In addition, executive functions were selectively affected by older age, with attention location and planning and initiation being the components that were most affected. PMID- 17336036 TI - Vocabulary and verbal fluency of bilingual and monolingual college students. AB - We assessed the English vocabulary and verbal fluency of college students who were either bilinguals who were born abroad and spoke English or monolingual speakers of English. We examined the relationship between age of arrival to the U.S. of bilinguals and their English vocabulary. The bilinguals' performance on English vocabulary was in the average range. However, despite arriving to the U.S. at a relatively young age, and having sufficient command of English to attend a competitive university, the bilinguals had lower receptive and expressive English vocabularies than their monolingual peers. Age of arrival was moderately correlated with English vocabulary scores. The younger the bilingual students were when they arrived to the U.S., the better their English vocabulary. Both groups had similar performance on phonetic fluency. However, the bilingual group performed significantly lower in semantic fluency. This pattern of performance in verbal fluency is consistent with that found in previous studies. PMID- 17336037 TI - An Internet-based investigation of the catastrophic misinterpretation model of panic disorder. AB - The catastrophic misinterpretation (CM) model of panic disorder proposes that spontaneous panic attacks are the result of interpretation of harmless autonomic arousal as precursors to physical (e.g., heart attack) or psychological (e.g., insanity) emergency. Mixed research findings to date have provided equivocal support. The body sensations interpretation questionnaire-modified was administered via Internet to investigate core assumptions of the model among 30 people with panic disorder (PD), 28 with social anxiety disorder (SAD), and 30 non-anxious controls. The PD group gave more harm-related interpretations of ambiguous internal stimuli than both other groups, and this tendency to interpret ambiguous stimuli catastrophically was not also apparent for external/general events. Furthermore, people with PD rated harm and anxiety outcomes as more catastrophic than non-anxious controls. Results substantially support the CM model although a modification is proposed. PMID- 17336038 TI - Mapping of quantitative trait loci affecting resistance/susceptibility to Sarcocystis miescheriana in swine. AB - The outcome of infectious diseases in vertebrates is under genetic control at least to some extent. In swine, e.g., marked differences in resistance/susceptibility to Sarcocystis miescheriana have been shown between Chinese Meishan and European Pietrain pigs, and these differences are associated with high heritabilities. A first step toward the identification of genes and polymorphisms causal for these differences may be the mapping of quantitative trait loci (QTLs). Considering clinical, immunological, and parasitological traits in the above model system, this survey represents the first QTL study on parasite resistance in pigs. QTL mapping was performed in 139 F(2) pigs of a Meishan/Pietrain family infected with S. miescheriana. Fourteen genome-wide significant QTLs were mapped to several chromosomal areas. Among others, major QTLs were identified for bradyzoite numbers in skeletal muscles (F = 17.4; p < 0.001) and for S. miescheriana-specific plasma IgG(2) levels determined 42 days p.i. (F = 20.9; p < 0.001). The QTLs were mapped to different regions of chromosome 7, i.e., to the region of the major histocompatibility complex (bradyzoites) and to an immunoglobulin heavy chain cluster, respectively. These results provide evidence for a direct and causal role for gene variants within these gene clusters (cis-acting) in differences in resistance to S. miescheriana. PMID- 17336039 TI - Environmental context differentially affects behavioral, leukocyte, cortisol, and interleukin-6 responses to low doses of endotoxin in the rhesus monkey. AB - Bacterial infections and proinflammatory cytokines induce behavioral and physiological responses associated with withdrawal and sickness behavior. These effects in rodents are often exacerbated by stressful environmental contexts. To model this synergistic effect of arousal and stress, low doses of lipopolysaccharide (LPS), 4 or 40ng/kg, were administered to rhesus monkeys in different environmental contexts. Activity, emotional and social behaviors, cortisol, interleukin-6 (IL-6), and peripheral leukocyte trafficking were assessed in 4 experiments: an initial 3h time-course in a novel cage (Experiment 1); an extended 24h time-course (Experiment 2); a highly arousing context in which an animal was engaged in the Human Intruder Paradigm (HIP, Experiment 3); and finally in an undisturbed context in their Home Cage (Experiment 4). The moderately arousing novel cage potentiated leukocyte, neutrophilic, IL-6, and cortisol changes as compared to the Home Cage. Unlike the social withdrawal seen in rodents, monkeys engaged in a marked increase in social behavior. IL-6 levels were positively correlated with Proximal Contact, which was induced to a greater degree by the higher dose of LPS. In contrast, the high arousal HIP condition appeared to obviate the effects of LPS. Thus, the rhesus monkey provides an excellent animal model for investigating the behavioral and physiological actions of endotoxemia, which are profoundly influenced by the situational context in which the individual is evaluated. PMID- 17336040 TI - Evaluation of effects of prenatal exposure to the cyanide and thiocyanate in wistar rats. AB - A study was performed at term and at weaning to verify the toxic effects of the prenatal exposure to potassium cyanide (KCN) and potassium thiocyanate (KSCN) in pregnant Wistar rats. Females received daily in drinking water the doses: 1, 3 and 30mg KCN/kg or 0.8, 2.4 and 24mg KSCN/kg from GD 6 to GD 20 and were euthanized on GD 20 (trial A) or one day after weaning (trial B). Skeletal and visceral analyses of the fetuses (trial A) were performed and samples of blood and different organs, from both dams (trials A and B) and weaned pups (trial B), were collected in order to perform the biochemical evaluation and histopathology. Results showed high thiocyanate levels in dams of the different experimental groups from both trials. The intensity of the histological lesions observed in dams of trial B was similar to that of trial A, except those lesions found in the pancreas. The histopathological study of this organ revealed loss of cells in the Islets of Langerhans from dams of trial A which received the highest dose of cyanide (CN). There was an increase in the number of biliary ducts in animals treated with the highest doses of both thiocyanate and cyanide. The histopathological study of the spleen and the lungs of experimental and control groups did not reveal any significant alteration. In relation to fetuses (trial A), the visceral and skeletal evaluations did not reveal any significant malformation; on the other hand, pups from trial B showed some histological alterations similar to those observed in their dams. It is concluded that the cyanide and/or thiocyanate promoted toxic effects in the fetuses some of which could also be observed at weaning. PMID- 17336042 TI - Statistical parameters of epileptiform brain activity differentiate frontal and temporal lobe patients. AB - Statistical properties of electromagnetic brain activity may increase the understanding of the human brain by providing precise numerical vales associated with neuronal activity. A statistical analysis was performed on frontal and temporal lobe patients to investigate possible differences between the two populations. Results were then compared to clinical results to confirm findings. Frontal lobe patients had a larger spatial distribution of interictal spikes when compared to temporal lobe patients. Statistical properties from interictal spike data may differentiate patients with frontal and temporal lobe epilepsy. PMID- 17336041 TI - JWA as a functional molecule to regulate cancer cells migration via MAPK cascades and F-actin cytoskeleton. AB - Mitogen activated protein kinase (MAPK) cascades are thought to mediate diverse biological functions such as cell growth, differentiation and migration. Activated MAPK may affect microtubule (MT) which is essential for cellular polarity, differentiation and motility. Data in this study show that JWA, a newly identified novel microtubule-associated protein (MAP) was essential for the rearrangement of F-actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As2O3) and phorbol ester (PMA). Over-expression of JWA alone in HeLa, B16 and HCCLM3 cancer cells effectively inhibited cellular migration; whereas, cellular migration was significantly accelerated when cells were deficient in JWA expression. The mechanism underlying these phenomena might be due to JWA affected F-actin rearrangement. Furthermore, JWA deficiency blocked anti-migratory effect produced by As2O3 but enhanced the migratory effect initiated by PMA in HeLa cells. JWA SDR-SLR motifs are not only critical for the MAPK cascades activation, but also for cell migration. Further studies found that JWA differentially regulated cell migration via ERK downstream effectors focal adhesion kinase (FAK) and cyclooxygenase-2 (COX-2). Therefore, JWA regulated tumor cellular migration might involve MAPK cascades activation and F-actin cytoskeleton rearrangement mechanisms. Our data provide an unexpected role for JWA in tumor cell migration behaviors. PMID- 17336043 TI - Corpora amylacea in mesial temporal lobe epilepsy: clinico-pathological correlations. AB - PURPOSE: To investigate the electro-clinical significance of premature accumulation of corpora amylacea (CoA) in the resected hippocampus of patients with medically refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). METHODS: We compared the clinical and EEG characteristics, and post-operative seizure outcome of 373 (mean age 29.4 years, range 7-55 years) surgically treated MTLE-HS patients with (MTLE-HS-CoA(+), n=129 [34.5%]) and without (MTLE-HS-CoA(-), n=244 [65.5%]) CoA. RESULTS: Age at surgery was significantly higher and duration of epilepsy before surgery was significantly longer for MTLE-HS-CoA(+) patients compared to MTLE-HS-CoA(-) patients. Although the distribution of interictal epileptiform EEG abnormalities did not differ, type 1 ictal EEG pattern was more frequent in MTLE-HS-CoA(+) patients. Among the 21 patients with major interictal psychosis detected prior to epilepsy surgery, 19 (90.5%) belonged to MTLE-HS-CoA(+) group. Schizophrenia-like psychosis was most prevalent. The post-operative seizure-free outcome was comparable, but significantly more MTLE-HS-CoA(-) patients were free of antiepileptic drugs. CONCLUSIONS: Overall, our observations support the hypothesis that the pathological process in MTLE-HS is progressive. MTLE-HS-CoA(+) patients are predisposed to increased psychiatric morbidity. In vivo detection of hippocampal CoA accumulation in the future will help us to understand the neurobiological significance of this phenomenon. PMID- 17336044 TI - Physicochemical properties affecting lipofection potency of a new series of 1,2 dialkoylamidopropane-based cationic lipids. AB - The in vitro transfection activity of a novel series of N,N'-diacyl-1,2 diaminopropyl-3-carbamoyl-(aminoethane) derivatives was evaluated against a mouse melanoma cell line at different +/- charge ratios, in the presence and absence of helper lipids. Only the unsaturated derivative N,N'-dioleoyl-1,2-diaminopropyl-3 carbamoyl-(aminoethane), (1,2lmp[5]) mediated significant increase in the reporter gene level which was significantly boosted in the presence of DOPE peaking at +/- charge ratio of 2. The electrostatic interactions between the cationic liposomes and plasmid DNA were investigated by gel electrophoresis, fluorescence spectroscopy, dynamic light scattering and electrophoretic mobility techniques. In agreement with the transfection results, 1,2lmp[5]/DOPE formulation was most efficient in associating with and retarding DNA migration. The improved association between the dioleoyl derivative and DNA was further confirmed by ethidium bromide displacement assay and particle size distribution analysis of the lipoplexes. Differential scanning calorimetry studies showed that 1,2lmp[5] was the only lipid that exhibited a main phase transition below 37 degrees C. Likewise, 1,2lmp[5] was the only lipid found to form all liquid expanded monolayers at 23 degrees C. In conclusion, the current findings suggest that high in vitro transfection activity is mediated by cationic lipids characterized by increased acyl chain fluidity and high interfacial elasticity. PMID- 17336045 TI - A convenient method for local drug administration at predefined sites in the entire gastrointestinal tract: experiences from 13 phase I studies. AB - For local administration of drugs or enzyme inhibitors in the human gut, a small bore, smooth tube was introduced through the nose, retrieved from the pharynx, equipped with a firm radio-opaque capsule, and swallowed. Peristalsis moves the capsule to the desired location in the gut where it is anchored before administration via the tube. Drug uptake is followed by plasma sampling. One capsule type is used for solutions, another for solid formulations. With solutions, repeated administrations could be done with the capsule being anchored for 24h or longer or, alternatively, at several locations along the gut. This communication presents the method and an overview of 13 uptake and enzyme/transporter localization studies. Altogether, 268 intubations were undertaken in a total of 128 subjects. Plasma concentrations found with terbutaline and metoprolol are presented showing that terbutaline has its best uptake in the upper small intestine, whereas metoprolol shows the same bioavailability along the whole gut. Subjects could undertake most of their normal activities while carrying the equipment. No serious adverse events (AEs) occurred. Possibly intubation-related AEs were abdominal pain (n=8) and constipation (n=5). In conclusion, the method has been found to be safe, convenient and multifunctional for studies of drug uptake at predetermined gut locations in healthy subjects. PMID- 17336046 TI - Detection of H5, H7 and H9 subtypes of avian influenza viruses by multiplex reverse transcription-polymerase chain reaction. AB - Subtype-specific multiplex reverse transcription-polymerase chain reaction (RT PCR) was developed to simultaneously detect three subtypes (H5, H7 and H9) of avian influenza virus (AIV) type A. The sensitivity of the multiplex RT-PCR was evaluated and compared to that of RT-PCR-enzyme-linked immunosorbent assay (ELISA) and conventional RT-PCR. While the sensitivity of the multiplex RT-PCR is as sensitive as the conventional RT-PCR, it is 10 times less sensitive than RT PCR-ELISA. The multiplex RT-PCR is also as sensitive as the virus isolation method in detecting H9N2 from tracheal samples collected at day 3 and 5 post inoculation. Hence, the developed multiplex RT-PCR assay is a rapid, sensitive and specific assay for detecting of AIV subtypes. PMID- 17336047 TI - Simultaneous identification of Bulbus Fritillariae cirrhosae using PCR-RFLP analysis. AB - Bulbus Fritillariae (BF) is the most commonly used antitussive herb in China. There are nine species of Fritillaria recorded as the drug BF in the Chinese Pharmacopoeia. Bulbus Fritillariae cirrhosae (BF cirrhosae) is a group that includes four species of BF; these four species come from wild sources with higher efficiency and lower toxicity compared to the other five species of BF. Due to reasons of carelessness and reduced costs, the other five species are often sold as BF cirrhosae. Analysis through appearance, microscopic and chemical techniques has limitations. Identifying botanical resources is a primary step in the standardization of herbal medicine. In the present article, the internal transcribed spacer 1 (ITS1) regions of the nuclear ribosomal DNA (nrDNA) of nine species and one variety of Fritillaria genus have been sequenced. A mutation site in the ITS1 region among BF cirrhosae and other species of BF has been found and can be recognized by the restriction endonuclease SmaI. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis of the nuclear ribosomal ITS1 region was used to differentiate BF cirrhosae from other species of BF and is a successful method in distinguishing the subgroups. PMID- 17336048 TI - Bioactive compounds from liverworts: Inhibition of lipopolysaccharide-induced inducible NOS mRNA in RAW 264.7 cells by herbertenoids and cuparenoids. AB - The inhibition of lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) by herbertenoids and cuparenoids isolated from liverworts in RAW 264.7 macrophages was evaluated. Among compounds tested, herbertenediol, cuparenediol, 1,2-diacetoxyherbertene and 2-hydroxy-4-methoxycuparene exhibited significant activity. For 2-hydroxy-4-methoxycuparene, chosen as representative compound, the strong inhibitory activity was related to the inhibition on LPS induced iNOS mRNA. The structure-activity relationship will be discussed. PMID- 17336049 TI - In vitro evaluation of human cytochrome P450 and P-glycoprotein-mediated metabolism of some phytochemicals in extracts and formulations of African potato. AB - African potato (Hypoxis hemerocallidea, AP) is a traditional herbal medicine widely used as an immune booster and also for the treatment of various ailments such as urinary diseases, prostrate hypertrophy and cancer. Amongst the chemical components contained in AP, the norlignan glycoside, hypoxoside (HYP) is purported to be the most important phytochemical in terms of AP's medicinal value. Additional constituents in AP include the sterols, beta-sitosterol (BSS), stigmasterol (STG), and the stanol, stigmastanol (STN). The potential of extracts of AP, AP formulations as well as HYP, its aglycone rooperol (ROP) and the sterols to inhibit in vitro metabolism of drug marker substrates by human cytochrome P450 (CYP) enzymes such as CYP3A4, 3A5 and CYP19 were investigated. Samples were also assessed for their effect on drug transport proteins such as P glycoprotein (P-gp). The effects on CYP-mediated metabolism were studied by fluorometric microtitre plate assay. The potential interaction with P-gp was investigated by measuring the efflux of the fluorescent dye rhodamine 123 (Rh 123) in the CaCo-2 (colon carcinoma) cell line. Various extracts of AP, AP formulations, only STG and the norlignans, in particular the aglycone ROP, exhibited inhibitory effects on CYP3A4-, 3A5- and 19-mediated metabolism. The extracts and the formulations that contained a significant amount of HYP showed high induction of P-gp compared to the positive control, ritonavir. Whilst extrapolation of the current in vitro findings to clinical effects may well be considered speculative, these in vitro data should be heeded as a signal of possible in vivo interactions. Appropriate measures are therefore necessary to explore the possibility of such in vitro-in vivo correlations. PMID- 17336050 TI - Introducing mechanical biological waste treatment in South Africa: a comparative study. AB - This paper presents the results of the first pilot project on mechanical biological waste treatment (MBWT) in South Africa. The study has shown that biological waste treatment in windrows using a passive aeration system that utilises thermal convection to drive the aeration process within a windrow of waste is appropriate for South Africa, in relation to low capital costs, low energy inputs, limited plant requirements and potential for labour-intensive operations. The influence of climate, waste composition and operational facilities was evaluated to optimise the treatment technique to local conditions. The maximum temperatures reached during the intensive thermophilic stage were effectively equivalent to the German experience. The lower CO2 production experienced in the South African trials was attributed to a different waste stream (high presence of plastics) due to the absence of a proper source separated waste collection system. An accurate adjustment of the input material (structural matter in particular) to the specific ambient conditions and irrigation during composting should result in higher organic carbon degradation efficiency in equivalent timeframes. This preliminary experience suggests that the applicability of MBWT in emerging countries, such as South Africa, is directly dependant on the mechanical treatment steps, available operational facilities and nature of the input material. PMID- 17336051 TI - Modelling municipal solid waste generation: a review. AB - The objective of this paper is to review previously published models of municipal solid waste generation and to propose an implementation guideline which will provide a compromise between information gain and cost-efficient model development. The 45 modelling approaches identified in a systematic literature review aim at explaining or estimating the present or future waste generation using economic, socio-demographic or management-orientated data. A classification was developed in order to categorise these highly heterogeneous models according to the following criteria--the regional scale, the modelled waste streams, the hypothesised independent variables and the modelling method. A procedural practice guideline was derived from a discussion of the underlying models in order to propose beneficial design options concerning regional sampling (i.e., number and size of observed areas), waste stream definition and investigation, selection of independent variables and model validation procedures. The practical application of the findings was demonstrated with two case studies performed on different regional scales, i.e., on a household and on a city level. The findings of this review are finally summarised in the form of a relevance tree for methodology selection. PMID- 17336052 TI - Multidimensional fatigue and its correlates in hospitalised advanced cancer patients. AB - Although fatigue is a multidimensional concept, multidimensional fatigue is rarely investigated in hospitalised cancer patients. We determined the levels and correlates of multidimensional fatigue in 100 advanced cancer patients admitted for symptom control. Fatigue dimensions were general fatigue (GF), physical fatigue (PF), reduced activity (RA), reduced motivation (RM) and mental fatigue (MF). Investigated correlates were tumour load, prior anti-tumour treatment, medication use, haemoglobin levels, serum biochemical variables, physical symptoms and mood. Median GF, PF and RA scores were very high; median RM and MF scores were moderate, and differed from the GF, PF and RA scores. Multiple regression analyses showed that symptoms and mood correlated with all fatigue dimensions. Each fatigue dimension had different relationships with other factors. Hospitalised advanced cancer patients differ in fatigue levels depending on the fatigue dimension, and each fatigue dimension has different correlates. The results confirm that fatigue should be regarded as a multidimensional concept. PMID- 17336053 TI - The role of self-reported stress in the development of breast cancer and prostate cancer: a prospective cohort study of employed males and females with 30 years of follow-up. AB - We investigate the association between psychological stress and breast cancer and, as oestrogen may provide a common mechanism, the association between stress and prostate cancer. A prospective study of 991 women and 5743 men employed in Scotland in the 1970s provided data. Risk exposure was measured by questionnaire and physical examination, routine data collection provided cancer outcomes over the subsequent 30 years. There was weak evidence of elevated incidences in those reporting moderate (breast cancer: hazard ratio [HR] 2.16, 95% CI 1.00-4.71; prostate cancer: HR 1.65, 95% CI 1.20-2.27) and high stress (breast cancer: HR 1.92, 95% CI 0.81-4.55; prostate cancer: HR 1.35, 95% CI 0.87-2.10) compared to those reporting low stress. These estimates are adjusted for socioeconomic circumstances and health-related behaviours. With no dose-response relationship and no established mechanism linking stress with breast and prostate cancer, confounding is the parsimonious explanation of these findings. PMID- 17336054 TI - Exatecan in pretreated adult patients with advanced soft tissue sarcoma: results of a phase II--study of the EORTC Soft Tissue and Bone Sarcoma Group. AB - No standard treatment is established for patients with advanced soft tissue sarcoma after previous chemotherapy with anthracyclines and ifosfamide, given either in combination or sequentially. Exatecan (DX-8951f) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself, topotecan or irinotecan. Since some activity against soft tissue sarcomas, especially leiomyosarcomas, has been reported for topoisomerase I-inhibitors, a study with a new and more potent agent seemed justified. We report on a prospective multicentre phase II study of Exatecan in adult soft tissue sarcomas failing 1 or 2 lines of chemotherapy in advanced phase, performed within the STBSG of EORTC. Thirty-nine patients (16 leiomyosarcomas and 23 other histologies) were included in two independent strata and received a total of 141 cycles (median 2). Median age was 61 years, range 25 76. Exatecan was given as i.v. infusion over 30 min at a dose of 0.5mg/m2 every day for five consecutive days, repeated every 21 days. Seventy-four percentage of cycles could be given without dose or schedule modification. The main toxicity was haematotoxicity with grade 3/4 neutropenia in 49%, grade 3/4 thrombocytopenia in 23%, and grade 3/4 anaemia in 15% of patients, respectively. Non haematological toxicity consisted mainly of grade 2/3 dyspnoea in 36% of patients and grade 2/3 fatigue in 28%. One treatment-related toxic death due to septic shock was reported. Best overall response was no change with 60% in the leiomyosarcoma group and 53% in the non-leiomysarcoma group, respectively. The 3 months progression-free survival estimates are 56% for leiomysarcomas and 26% for other histologies, respectively. Using a two-step statistical design, the trial was stopped after the first step in both strata, due to lack of activity. In pretreated soft tissue sarcoma patients, Exatecan is well tolerated but does not achieve any objective responses. However, with respect to progression-free survival, Exatecan did show some activity in leiomyosarcomas. PMID- 17336055 TI - Plant availability of nutrients recovered as solids from human urine tested in climate chamber on Triticum aestivum L. AB - Recovered nutrients by freezing-thawing from human urine in combination with struvite precipitation and nitrogen adsorption on zeolite and activated carbon have been tested in pot trials with wheat, Triticum aestivum L., in a climate chamber during 21 days. A simple test design using sand as substrate was chosen to give a first, general evaluation of the nutrient (P and N) availability from these sources. Dry weight, plant growth morphology, total-P and total-N were analysed. The tests show a slow-release of nutrients (P and N) from struvite and from N-adsorbents. The nitrogen in all treatments was in the deficiency range for optimum yield for wheat. Higher pH than usual for soil tests contributed to the difficulties in plant uptake, especially in the pots with only struvite (with highest MgO addition) as nutrient source. PMID- 17336056 TI - Immunological cell and serum metabolite response of 60-week-old commercial laying hens to an alfalfa meal molt diet. AB - The practice of induced molting involves the restriction of light, feed removal and optionally water for 5-14 days. However, there is growing concern regarding feed removal and animal welfare issues. With this in mind, alternative diets have been developed to produce similar molting effects as that of feed deprivation. Alfalfa, which largely consists of insoluble fiber, can be used as a molting diet. In this study, heterophil and lymphocyte counts, serum chemistry, and organ weight parameters were evaluated in hens that were deprived of feed or fed alfalfa during a nine day induced molt. Full-fed hens were used as the control. Blood serum parameters assessed included calcium, magnesium, glucose, total protein, ketone bodies, uric acid, and cholesterol. White blood cells were counted and categorized by cell type. On the ninth day of the trial, the hens were euthanized and the liver, spleen, heart, intestine, pancreas, ovary, oviduct, and kidney were collected and weighed. On day 8 birds molted with alfalfa or by feed deprivation had significantly higher (P<0.05) levels of ketone bodies and cholesterol and lower levels of calcium, and magnesium compared to the full-fed hens while birds molted by feed deprivation exhibited significantly lower levels of uric acid. Birds molted by both methods exhibited significant reductions in ovary, oviduct, liver and pancreas weights and increased spleen weights when compared to the non-molted hens. On days 0, 2, and 6 there were no significant differences (P>0.05) in either heterophil or lymphocyte percentages. However, heterophil percentages were higher in feed withdrawal birds than full fed birds on day 4 but lymphocyte percentages were higher in full-fed birds compared to feed withdrawal birds. On day 8 of the induced molt lymphocyte percentages were higher from full-fed birds when compared to feed withdrawal birds but no significant differences were detectable for heterophil percentages. Based on reproductive organ weight loss and changes in serum and immunological responses of birds during molt, it appears that alfalfa meal can be an effective molt induction alternative. PMID- 17336057 TI - Use of plant residues for improving soil fertility, pod nutrients, root growth and pod weight of okra (Abelmoschus esculentum L). AB - The effect of wood ash, sawdust, ground cocoa husk, spent grain and rice bran upon root development, ash content, pod yield and nutrient status and soil fertility for okra (Abelmoschus esculentum L NHAe 47 variety) was studied. The five organic fertilizer treatments were compared to chemical fertilizer (400kg/ha/crop NPK 15-15-15) and unfertilized controls in four field experiments replicated four times in a randomized complete block design. The results showed that the application of 6tha(-1) of plant residues increased (P<0.05) the soil N, P, K, Ca, Mg, pH, and SOM; pod N, P, K, Ca, Mg and ash; root length; and pod yield of okra in all four experiments relative to the control treatment. For instance, spent grain treatment increased the okra pod yield by 99%, 33%, 50%, 49%, 65% and 67% compared to control, NPK, wood ash, cocoa husk, rice bran and sawdust treatments respectively. In the stepwise regression, out of the total R(2) value of 0.83 for the soil nutrients to the pod yield of okra; soil N accounted for 50% of the soil fertility improvement and yield of okra. Spent grain, wood ash and cocoa husk were the most effective in improving okra pod weight, pod nutrients, ash content, root length and soil fertility whereas the rice bran and sawdust were the least effective. This was because the spent grain, wood ash and cocoa husk had lower C/N ratio and higher nutrient composition than rice bran and sawdust, thus, the former enhanced an increase in pod nutrients, composition for better human dietary intake, increased the root length, pod weight of okra and improved soil fertility and plant nutrition crop. The significance of the increases in okra mineral nutrition concentration by plant residues is that consumers will consume more of these minerals in their meals and monetarily spend less for purchasing vitamins and mineral supplement drugs to meet health requirements. In addition, the increase in plant nutrition and soil fertility would help to reduce the high cost of buying synthetic inorganic fertilizers and maintain the long term productivity of soils for sustainable cultivation of okra. PMID- 17336058 TI - Fermentative hydrogen gas production using biosolids pellets as the inoculum source. AB - Biosolids pellets produced from anaerobically digested municipal wastewater sludge by drying to greater than 90% total solids at 110-115 degrees C for at least 75 min, were tested for their suitability as an inoculum source for fermentative hydrogen production. The hydrogen recoveries (mg gaseous H(2) produced as COD/mg added substrate COD) for glucose-fed batch systems were equal, 20.2-21.5%, between biosolids pellets and boiled anaerobic digester sludge as inoculum sources. Hydrogen recoveries from primary sludge were 2.4% and 3.5% using biosolids pellets and boiled sludge, respectively, and only 0.2% and 0.8% for municipal wastewater. Biosolids pellets should be a practical inoculum source for fermentative hydrogen reactors, although the effectiveness will depend on the wastewater treated. PMID- 17336059 TI - Biosorbents prepared from wood particles treated with anionic polymer and iron salt: effect of particle size on phosphate adsorption. AB - Biomass-based adsorbents have been widely studied as a cost-effective and environmentally-benign means to remove pollutants and nutrients from water. A two stage treatment of aspen wood particles with solutions of carboxymethyl cellulose (CMC) and ferrous chloride afforded a biosorbent that was effective in removing phosphate from test solutions. FTIR spectroscopy of the biosorbent samples showed a decrease in the intensity of the carboxylate signal coinciding with a decrease in particle size. Elemental analysis results showed the iron content of both the biosorbent samples, and wood particles treated with ferrous chloride alone, to also decrease with particle size. The relationship between iron content and particle size for the biosorbent samples appeared to be a function of both the amount of CMC-Fe complex and the efficiency of removing free iron ions after treating. Sorption testing results showed a strong linear correlation between the phosphorous uptake capacities and the iron contents of the samples adjusted for losses of iron during testing. As anticipated, pretreating with the anionic polymer provided additional sites to complex iron and thereby imparted a greater phosphorous uptake capacity. Although the larger wood particles provided a greater amount of iron for phosphate removal, smaller wood particles may be preferred since they afforded the lowest release of iron relative to the amount of phosphate removed. PMID- 17336060 TI - Are Phragmites australis enzymes involved in the degradation of the textile azo dye acid orange 7? AB - The role of antioxidant and detoxification enzymes of Phragmites australis, in the degradation of an azo dye, acid orange 7 (AO7), was studied. Activities of several enzymes involved in plant protection against stress were assayed through the activity characterization of superoxide dismutase (SOD), peroxidases (POD), catalase (CAT), ascorbate peroxidase (APOX), dehydroascorbate reductase (DHAR) and glutathione S-transferase (GST), obtained from P. australis crude extracts of leaves, stems and roots. A sub-surface vertical flow constructed wetland, planted with P. australis was used to test the plants response to the AO7 exposure at two different concentrations (130 and 700 mg l(-1)). An activity increase was detected for an AO7 concentration of 130 mg l(-1) for most enzymes studied (SOD, CAT and APOX), especially in leaves, suggesting a response of the reactive oxygen species scavenging enzymes to the chemical stress imposed. GST activity increase in this situation can also be interpreted as an activation of the detoxification pathway and subsequent AO7 conjugation. A totally different behaviour was observed for AO7 at 700 mg l(-1). An evident decrease in activity was observed for SOD, CAT, APOX and GST, probably due to enzymatic inhibition by AO7. Contrarily, DHAR activity augmented drastically in this situation. POD activity was not greatly affected during trial. Altogether these results suggest that P. australis effectively uses the ascorbate-glutathione pathway for the detoxification of AO7. PMID- 17336061 TI - Fuel ethanol production: process design trends and integration opportunities. AB - Current fuel ethanol research and development deals with process engineering trends for improving biotechnological production of ethanol. In this work, the key role that process design plays during the development of cost-effective technologies is recognized through the analysis of major trends in process synthesis, modeling, simulation and optimization related to ethanol production. Main directions in techno-economical evaluation of fuel ethanol processes are described as well as some prospecting configurations. The most promising alternatives for compensating ethanol production costs by the generation of valuable co-products are analyzed. Opportunities for integration of fuel ethanol production processes and their implications are underlined. Main ways of process intensification through reaction-reaction, reaction-separation and separation separation processes are analyzed in the case of bioethanol production. Some examples of energy integration during ethanol production are also highlighted. Finally, some concluding considerations on current and future research tendencies in fuel ethanol production regarding process design and integration are presented. PMID- 17336062 TI - Sulfonamide-related conformational effects and their importance in structure based design. AB - Structure-based design (SBD) is a challenging endeavour since even localised SAR can hardly ever be explained by the variation of just one dominating factor. Here, we present a rare example where structural information combined with ab initio calculations clearly indicate that the observed difference in biological activity is dominated by conformational effects. The learnings discussed are successfully put to the test and have the potential to be of general use as a qualitative guide in SBD efforts. PMID- 17336063 TI - Synthesis and in vivo antihyperglycemic activity of nature-mimicking furanyl-2 pyranones in STZ-S model. AB - Various nature-mimicking pyranones such as 6-(2,5-dimethylfuran-3-yl)-pyran-2-one and 6-(furan-2-yl)-pyran-2-one derivatives were synthesized and evaluated for their in vivo antihyperglycemic activity in sucrose-loaded streptozotocin-induced diabetic rat model. Five of the test compounds showed significant lowering of plasma glucose level in STZ-S model. PMID- 17336064 TI - Probing acid replacements of thiophene PTP1B inhibitors. AB - The following account describes our systematic effort to replace one of the carboxylate groups of our diacid thiophene PTP1B inhibitors. Active hits were validated using enzymatic assays before pursuing efforts to improve the potency. Only when the C2 carboxylic acid was replaced with another ionizable functional group was reversible and competitive inhibition retained. Use of a tetrazole ring or 1,2,5-thiadiazolidine-3-one-1,1-dioxide as a carboxylate mimetic led to the discovery of two unique starting series that showed improved permeability (PAMPA) and potency of the order of 300nM. The SAR from these efforts underscores some of the major challenges in developing small molecule inhibitors for PTP1B. PMID- 17336065 TI - Indole derivatives as potent inhibitors of 5-lipoxygenase: design, synthesis, biological evaluation, and molecular modeling. AB - A series of novel indole derivatives was designed, synthesized and evaluated by cell-based assays for their inhibitory activities against 5-LOX in rat peritoneal leukocytes. Most of them (30 out of 35) showed an inhibitory potency higher than the initial screening hit 1a (IC(50)=74 microM). Selected compounds for concentration-response studies showed prominent inhibitory activities with IC(50) values ranging from 0.74 microM to 3.17 microM. Four compounds (1m, 1s, 4a, and 6a) exhibited the most potent inhibitory activity compared to that of the reference drug (Zileuton), with IC(50) values less than 1 microM. Molecular modeling studies for compounds 1a, 3a, 4a, and 6a were also presented. The excellent in vitro activities of this class of compounds may possess potential for the treatment of LT-related diseases. PMID- 17336066 TI - Synthesis and characterisation of a new pH-sensitive amphotericin B- poly(ethylene glycol)-b-poly(L-lysine) conjugate. AB - This paper reports on the synthesis, characterisation, and efficiency of a new intravenous conjugate of amphotericin B (AMB). Twelve molecules of AMB were attached to block copolymer poly(ethylene glycol)-b-poly(L-lysine) via pH sensitive imine linkages. In vitro drug release studies demonstrated the conjugate (M(w)=26,700) to be relatively stable in human plasma and in phosphate buffer (pH 7.4, 37 degrees C). Controlled release of AMB was observed in acidic phosphate buffer (pH 5.5, 37 degrees C) with the half-life of 2 min. The LD(50) value determined in vivo (mouse) is 45 mg/kg. PMID- 17336067 TI - A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex. AB - Mutations in the gene encoding fukutin related protein (FKRP) produce a spectrum of disease including congenital muscular dystrophy and limb girdle muscular dystrophy. FKRP is one member of a class of molecules thought to be glycosyltransferases that mediate O-linked glycosylation. The primary target of these glycosyltransferases is thought to be dystroglycan. We now report two unrelated Mexican children with congenital muscular dystrophy who each have the identical, novel 1387A>G, N463D mutation. Muscle biopsies from these children show a reduction of alpha-dystroglycan and also show reduction of beta dystroglycan, and alpha-, beta-, and gamma-sarcoglycan, suggesting that FKRP mutations can perturb membrane associated proteins beyond dystroglycan. PMID- 17336068 TI - The effect of respiratory muscle endurance training in patients with myasthenia gravis. AB - We tested the effect of a home-based respiratory muscle endurance training in patients with mild to moderate generalized myasthenia gravis (MG) on Besinger score, lung function and respiratory muscle endurance. Ten patients performed respiratory muscle endurance training in form of normocapnic hyperpnea training at 50-60% of their maximal voluntary ventilation over 4-6 weeks. MG score, lung function and respiratory endurance were assessed before and after training period. The training significantly increased respiratory endurance from 8.4+/-0.9 min to 17.1+/-1.3 min (p<0.001) and total ventilatory volume from 555+/-87 L to 1081+/-127 L (p=0.004). About 25% of this gain was lost after 3-5 months of detraining. The remaining 75% gain might result from improved neuromuscular coordination rather than muscular training. MG score and lung function, however, did not change. Patients assessed the training effects on physical fitness and respiration as positive. In conclusion, respiratory muscle endurance training can be useful for MG patients as it is enhancing respiratory muscle endurance. PMID- 17336069 TI - Paraneoplastic myopathy: response to intravenous immunoglobulin. AB - Necrotizing myopathy is an unusual and severe form of paraneoplastic myopathy in which inflammation is minimal or absent. We report two cases of necrotizing myopathy which demonstrated significant response to intravenous immunoglobulin (IVIG) (one in spite of tumor progression). A third case represents the first association of anti-signal recognition particle (anti-SRP) syndrome with large cell lung cancer. These cases highlight the role of histopathologic diagnosis in directing the treatment of paraneoplastic myopathy, and the role for IVIG in treatment of the syndrome. PMID- 17336070 TI - Concurrent validity and intrasession reliability of the IDEEA accelerometry system for the quantification of spatiotemporal gait parameters. AB - The aim of this pilot study was to evaluate concurrent validity and intrasession reliability of the IDEEA (Minisun, Fresno, CA) accelerometry system (and associated software) with force plate measurements for spatiotemporal gait variables recorded during normal walking. Ten healthy individuals were asked to walk at a self-selected comfortable speed, over five multicomponent force plates embedded into the walkway floor. For each trial, spatiotemporal gait parameters (single support time, cadence, speed, step and stride length) obtained by the force plates were compared to those recorded by IDEEA. Concurrent (criterion related) validity between the two systems was analysed with intraclass correlation (ICC) (2,1). Intrasession reliability was quantified by using coefficient of variations (CV) and ICC. For the ensemble of the parameters, ICC (2,1) ranged between 0.998 (cadence) and 0.784 (step length right) (p<0.001 0.01). However, speed, step length and stride length were significantly lower for IDEEA (~7%; p<0.001) compared to force plate data. Intrasession reliability of IDEEA was excellent, with CV lower than 5.7 and ICC higher than 0.961. The present accelerometry system demonstrated strong concurrent validity for the assessment of spatiotemporal gait parameters. However, spatial variables (stride and step length) and walking speed were significantly underestimated compared with analyses using force plates. PMID- 17336071 TI - I will survive: DNA protection in bacterial spores. AB - Dormant spores of Bacillus, Clostridium and related species can survive for years, largely because spore DNA is well protected against damage by many different agents. This DNA protection is partly a result of the high level of Ca(2+)-dipicolinic acid in spores and DNA repair during spore outgrowth, but is primarily caused by the saturation of spore DNA with a group of small, acid soluble spore proteins (SASP), which are synthesized in the developing spore and then degraded after completion of spore germination. The structure of both DNA and SASP alters upon their association and this causes major changes in the chemical and photochemical reactivity of DNA. PMID- 17336072 TI - IL-10, T cell exhaustion and viral persistence. AB - Viral infections can have one of two outcomes: control of viral replication and acute infection or viral persistence and chronic infection. It is clear that both pathogen and host characteristics influence the acute versus chronic outcome of viral infection. The early events in the host immune response that favor immunosuppression and viral persistence, however, have remained poorly understood. Using the well-characterized mouse model of acute versus chronic lymphocytic choriomeningitis virus (LCMV) infection, two groups have recently identified the interleukin-10 (IL-10)/IL-10R pathway as a key regulator of acute versus chronic infection. Blockade of IL-10R converted a chronic LCMV infection into a rapidly controlled acute viral infection and prevented the functional exhaustion of memory T cells. These insights into the role of IL-10 in the establishment of chronic infection could lead to new therapeutic opportunities during human infections with pathogens such as HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV). PMID- 17336073 TI - Free radical trapping properties of several ethyl-substituted derivatives of 5 ethoxycarbonyl-5-methyl-1-pyrroline N-oxide (EMPO). AB - The spin trapping behavior of several ethyl-substituted EMPO derivatives, cis- and trans-5-ethoxycarbonyl-3-ethyl-5-methyl-pyrroline N-oxide (3,5-EEMPO), 5 ethoxycarbonyl-4-ethyl-5-methyl-pyrroline N-oxide (4,5-EEMPO), cis- and trans-5 ethoxycarbonyl-5-ethyl-3-methyl-pyrroline N-oxide (5,3-EEMPO), and 5 ethoxycarbonyl-5-ethyl-4-methyl-pyrroline N-oxide (5,4-EEMPO), toward a series of different oxygen- and carbon-centered radicals, is described. Considerably different stabilities of the superoxide adducts (ranging from about 12 to 55 min) as well as the formation of other radical adducts were observed. PMID- 17336074 TI - 5-Alkynyl-2'-deoxyuridines: chromatography-free synthesis and cytotoxicity evaluation against human breast cancer cells. AB - Starting with 5-iodo-2'-deoxyuridine, a series of 5-alkynyl-2'-deoxyuridines (with n-propyl, cyclopropyl, 1-hydroxycyclohexyl, p-tolyl, p-tert-butylphenyl, p pentylphenyl, and trimethylsilyl alkyne substituents) have been synthesized via the palladium-catalyzed (Sonogashira) coupling reaction followed by a simplified isolation protocol (76-94% yield). The cytotoxic activity of modified nucleosides against MCF-7 and MDA-MB-231 human breast cancer cells has been determined in vitro. 5-Ethynyl-2'-deoxyuridine, the only nucleoside in the series containing a terminal acetylene, is the most potent inhibitor with IC(50) (microM) 0.4+/-0.3 for MCF-7 and 4.4+/-0.4 for MDA-MB-231. PMID- 17336075 TI - Computational approach to the basicity of a series of alpha1-adrenoceptor ligands in aqueous solution. AB - In order to design any new potential drug, it is crucial to know their corresponding pK(a) since their protonation state will be critical in the ligand receptor interaction and it will play an essential role in their pharmacokinetic profile. Several authors have developed approaches for the computational determination of pK(a) which involve the use of a thermodynamic cycle relating pK(a) to the gas-phase proton basicity via the solvation energies of the products and the reactants. Such methods are very dependent on the solvation model used and the nature of the system. The theoretical pK(a) of a number of agonists and antagonists of the alpha1A-adrenoceptor has been computed and the performance of this approach has been tested through comparison with the available and/or measured experimental pK(a) values. PMID- 17336076 TI - Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease. AB - Huntington's disease (HD) is a devastating neurodegenerative disease characterized by the selective loss of neurons in the striatum and cerebral cortex. This study tested the hypothesis that an adenoassociated viral (AAV2) vector encoding for the trophic factor neurturin (NTN) could provide neuroprotection in the rat 3-nitropropionic acid (3NP) model of HD. Rats received AAV2-NTN (CERE-120), AAV2-eGFP or Vehicle, followed 4 weeks later by the mitochondrial toxin 3NP. 3NP induced motor impairments were observed on the rotarod test, the platform test, and a clinical rating scale in all groups. However, each of these deficits was attenuated by AAV2-NTN (CERE-120). Stereological counts revealed a significant protection of NeuN-ir striatal neurons from 3NP toxicity by AAV2-NTN. These data support the concept that AAV2 NTN might be a valuable treatment for patients with Huntington's disease. PMID- 17336077 TI - MPTP and DSP-4 susceptibility of substantia nigra and locus coeruleus catecholaminergic neurons in mice is independent of parkin activity. AB - Mutations in the parkin gene cause autosomal recessive familial Parkinson's disease (PD). Parkin-deficient mouse models fail to recapitulate nigrostriatal dopaminergic neurodegeneration as seen in PD, but produce deficits in dopaminergic neurotransmission and noradrenergic-dependent behavior. Since sporadic PD is thought to be caused by a combination of genetic susceptibilities and environmental factors, we hypothesized that neurotoxic insults from catecholaminergic toxins would render parkin knockout mice more vulnerable to neurodegeneration. Accordingly, we investigated the susceptibility of catecholaminergic neurons in parkin knockout mice to the potent dopaminergic and noradrenergic neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) respectively. We report that nigrostriatal dopaminergic neurons in parkin knockout mice do not show increased susceptibility to the parkinsonian neurotoxin, MPTP, in acute, subacute and chronic dose regimens of the neurotoxin. Additionally, parkin knockout mice do not show increased vulnerability to the noradrenergic neurotoxin, DSP-4, regarding levels of norepinephrine in cortex, brain stem and spinal cord. These findings suggest that absence of parkin in mice does not increase susceptibility to the loss of catecholaminergic neurons upon exposure to both dopaminergic and noradrenergic neurotoxins. PMID- 17336078 TI - Silencing of the Charcot-Marie-Tooth associated MTMR2 gene decreases proliferation and enhances cell death in primary cultures of Schwann cells. AB - Loss of function of the myotubularin (MTM)-related protein 2 (MTMR2) in Schwann cells causes Charcot-Marie-Tooth disease type 4B1, a severe demyelinating neuropathy, but the consequences of MTMR2 disruption in Schwann cells are unknown. We established the expression profile of MTMR2 by real-time RT-PCR during rat myelination and showed it to be preferentially expressed at the onset of the myelination period. We developed a model in which MTMR2 loss of function was reproduced in primary cultures of Schwann cells by RNA interference. We found that depletion of MTMR2 in Schwann cells decreased their rate of proliferation. Furthermore, when cultivated in serum-free medium, MTMR2 depletion increased the number of Schwann cells that died by a caspase-dependent process. These results support the hypothesis that loss of MTMR2 in patients, by decreasing Schwann cells proliferation and survival, may impair the first stages of myelination of the peripheral nervous system. PMID- 17336079 TI - Polysialylation of NCAM is upregulated by hyperthermia and participates in heat shock preconditioning-induced neuroprotection. AB - "Brain tolerance"--a phenomenon in which a subtoxic challenge confers resistance to subsequent brain injuries--provides an ideal opportunity for investigating endogenous neuroprotective mechanisms. We investigated the potential role of the polysialylated (PSA) form of neural cell adhesion molecule (NCAM), which is thought to play a key role in plasticity. In a model where prior exposure to heat shock protects against kainate-induced cell damage in the hippocampus, we show that hyperthermia upregulates PSA-NCAM expression for at least 1 week, without affecting neurogenesis. Pharmacological manipulation of heat shock protein (HSP) expression demonstrates a tight positive link between HSP70 and PSA-NCAM. Finally, the presence of PSA was functionally linked to brain tolerance, as protection against kainate-induced cell death by heat shock pre-exposure was abolished in the absence of NCAM polysialylation. The upregulation of PSA-NCAM by hyperthermia may have a significant impact on hippocampal plasticity, permitting induction of the complex molecular cascade responsible for neuroprotection. PMID- 17336080 TI - Primary triple valve surgery for advanced rheumatic heart disease in Mainland China: a single-center experience with 871 clinical cases. AB - BACKGROUND: Triple valve surgery (TVS) is still of choice for advanced rheumatic heart disease (RHD), which has been associated with reported poor early and late outcomes. We describe the short- and long-term results after TVS in last two decades in Mainland China. METHODS: From January 1985 to January 2005, a total of 871 patients (217 men, 654 women), with mean age of 42+/-11 years, underwent primary TVS for isolated advanced RHD. All patients received replacement procedures in mitral and aortic position (845 mechanical, 26 bioprosthetic), and 840 patients received repair procedures and the other 31 received replacement procedures in tricuspid position (9 mechanical, 22 bioprosthetic). Preoperative, perioperative, and postoperative data were retrospectively analyzed and risk factors affecting early and late survival were evaluated. RESULTS: The 30-day hospital mortality was 8% (n=71). Presence of ascites, New York Heart Association (NYHA) class IV and lower left ventricular ejection fraction (LVEF) were identified as independent risk factors for hospital mortality. Overall long-term survival rate was 71%+/-3% at 5 years, and 59%+/-5% at 10 years. The cardiac survival rate was 75%+/-3% at 5 years and 63%+/-4% at 10 years. The event-free survival rate at 5 years and 10 years was 61%+/-6% and 41%+/-13%, respectively. Multivariate analysis revealed advanced age, NYHA class IV and lower LVEF were associated with increased late mortality. The freedom from thromboembolism and anticoagulation-related hemorrhage at 10 years was 90%+/-4% and 81%+/-5%, respectively. Of the 508 patients still alive, 376 (74%) were in NYHA class I and II. CONCLUSIONS: Primary TVS for advanced RHD appears to offer satisfactory short and long-term results with excellent symptomatic improvement. Cardiac-related late mortality following TVS may be improved by early surgical treatment before NYHA class IV or deterioration of LVEF occurs. PMID- 17336081 TI - European Working Time Directive implementation and cardiothoracic training: larger centers may optimise training. PMID- 17336083 TI - Long-term lung function following videothoracoscopic talc poudrage for primary spontaneous recurrent pneumothorax. AB - OBJECTIVE: Some concern still exists regarding long-term lung function following videothoracoscopic talc poudrage for primary spontaneous pneumothorax (PSP). We evaluated lung function at 5 years in a series of 100 patients surgically treated for PSP. METHODS: Out of 1065 patients treated for PSP by means of videothoracoscopic talc poudrage from September 1995 to January 2006, we consecutively enrolled 50 patients (33 males, 17 females, mean age: 24.22 years, median age: 24 years; range: 13-40 years) (group A) with no recurrence for functional evaluation with measurement of static and dynamic volumes (FEV1-FVC TLC-RV), and DLCO at 60 months after surgery. Fifty patients (35 males, 15 females, mean age: 23.56 years; median age: 22.5 years; range: 16-37 years) underwent same pulmonary function tests 5 years after simple drainage for recurrent PSP because of refusal of surgery (group B). RESULTS: Pulmonary function tests showed (mean % value+/-SD for group A vs group B): FEV1 93+/-6.6 versus 95.4+/-6.4; FVC 98+/-6.5 versus 100.1+/-6.9; TLC 91.7+/-7.7 versus 94.36+/ 5.8; RV 97+/-7 versus 99.2+/-4.9; DLCO 91.4+/-2.8 versus 91.98+/-4.2. No patient in both groups showed FEV1<80%. Analysis of mean difference of pulmonary function values was computed between group A and group B patients. CONCLUSIONS: No statistically significant differences in long-term lung function have been found between patients treated with pleural drainage only versus patients treated with videothoracoscopic talc poudrage for PSP. Lung function is not impaired by videothoracoscopic talc poudrage. PMID- 17336082 TI - Brain oxygen and metabolism is dependent on the rate of low-flow cardiopulmonary bypass following circulatory arrest in newborn piglets. AB - OBJECTIVE: To determine the optimum rate of low-flow hypothermic cardiopulmonary bypass (LF), following circulatory arrest (DHCA) on brain oxygenation (bO(2)), extracellular dopamine (DA), phosphorylation of select neuroregulatory proteins responsible for neuronal injury, and survival following ischemic brain injury: CREB, Erk1/2, Akt, Bcl-2, and Bax. METHODS: The piglets were placed on cardiopulmonary bypass (CPB) and cooled to 18 degrees C. They were then subjected to 30 min of DHCA followed by 1h of LF at 20, 50, or 80 ml/(kg/min), rewarmed, separated from CPB, and maintained for 2h. The bO(2) was measured by quenching of phosphorescence; DA by microdialysis; phosphorylation of CREB, ERK1/2, Akt, Bcl 2, and Bax by Western blots. The results are means+/-SD for seven experiments. RESULTS: Pre-bypass bO(2) was 47.4+/-4.2 mmHg and decreased to 1.9+/-0.8 mmHg during DHCA. At the end of LF at 20, 50, and 80 ml/(kg/min), bO(2) was 11.8+/ 1.6, 26+/-1.8, and 33.9+/-2.6 mmHg, respectively. The DA increased 510-fold relative to control (p<0.001) by 15 min of LF-20 with maximum increase occurring at 45 min. With LF-50, increase in DA was not statistically significant and no increase was observed when LF-80 was used. Bcl-2 immunoreactivity increased after LF-50 and LF-80 (140+/-14.5%, p<0.05 and 202+/-34%, p<0.05, respectively). Neither flow increased Bax immunoreactivity. The ratio of Bcl-2/Bax, pCREB, pAkt, pErk increased significantly with increasing the flow rate of LF. CONCLUSIONS: The protective effect of LF following DHCA on brain metabolism is dependent on the flow rate. Flow-dependent increase in pCREB, pErk1/2, pAkt, increase in Bcl 2/Bax, and decrease in DA indicated that to minimize DHCA-dependent neuronal injury, LF flow should be above 50 ml/(kg/min). PMID- 17336084 TI - Cardiac tamponade in patient with giant thoraco-abdominal aortic aneurysm. PMID- 17336086 TI - Critical review: updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients--May 2006. AB - In light of recent reports of osteonecrosis of the jaw (ONJ) in cancer patients whose treatment regimens include an intravenous bisphosphonate, Novartis convened an international advisory board of experts in the fields of oral surgery and pathology, medical oncology, metabolic bone disease, and orthopedics to review existing data and provide updated recommendations on the clinical diagnosis, prevention, and management of ONJ in the oncology setting. Recommendations were developed to help guide healthcare professionals in early diagnosis and patient management. It is recommended that patients be encouraged to receive a dental examination prior to initiating bisphosphonate therapy and, if possible, complete any necessary dental procedures (e.g., tooth extraction) prior to initiating bisphosphonate therapy. Patients should receive regular dental visits during bisphosphonate therapy. Patients should be encouraged to practice good oral hygiene and minimize possible jaw trauma. If possible, patients should avoid dental surgery during treatment with bisphosphonates. If exposed bone is observed or reported in the oral cavity at any time (suspected ONJ), refer the patient to a dental professional immediately. PMID- 17336087 TI - Mechanisms of resistance to cisplatin and carboplatin. AB - While cisplatin and carboplatin are active versus most common cancers, epithelial malignancies are incurable when metastatic. Even if an initial response occurs, acquired resistance due to mutations and epigenetic events limits efficacy. Resistance may be due to excess of a resistance factor, to saturation of factors required for tumor cell killing, or to mutation or alteration of a factor required for tumor cell killing. Platinum resistance could arise from decreased tumor blood flow, extracellular conditions, reduced platinum uptake, increased efflux, intracellular detoxification by glutathione, etc., decreased binding (e.g., due to high intracellular pH), DNA repair, decreased mismatch repair, defective apoptosis, antiapoptotic factors, effects of several signaling pathways, or presence of quiescent non-cycling cells. In lung cancer, flattening of dose-response curves at higher doses suggests that efficacy is limited by exhaustion of something required for cell killing, and several clinical observations suggest epigenetic events may play a major role in resistance. PMID- 17336088 TI - The LXR agonist TO901317 selectively lowers hippocampal Abeta42 and improves memory in the Tg2576 mouse model of Alzheimer's disease. AB - Recent studies show that intracellular cholesterol levels can modulate the processing of amyloid precursor protein to Abeta peptide. Moreover, cholesterol rich apoE-containing lipoproteins may also promote Abeta clearance. Agonists of the liver X receptor (LXR) transcriptionally induce genes involved in intracellular lipid efflux and transport, including apoE. Thus, LXR agonists have the potential to both inhibit APP processing and promote Abeta clearance. Here we show that LXR agonist, TO901317, increased hippocampal ABCA1 and apoE and decreased Abeta42 levels in APP transgenic mice. TO901317 had no significant effects on levels of Abeta40, full length APP, or the APP processing products. Next, we examined the effects of TO901317 in the contextual fear conditioning paradigm; TO901317 completely reversed the contextual memory deficit in these mice. These data demonstrate that LXR agonists do not directly inhibit APP processing but rather facilitate the clearance of Abeta42 and may represent a novel therapeutic approach to Alzheimer's disease. PMID- 17336089 TI - Dynamic changes in CREB phosphorylation and neuroadaptive gene expression in area V1 of adult monkeys after monocular enucleation. AB - Our understanding of the molecular events that emerge after change in sensory input remains elusive, especially with regard to mature area V1. Here, we characterized P-CREB expression in area V1 of monkeys at multiple time-points after monocular enucleation (ME) to assess the possible contribution of CREB in visually deprived neocortex. Immunoblot assays and immunostainings showed that P CREB is dynamically regulated in adult area V1, reaching a peak level between 5 and 30 days after ME, and becoming reduced at the 90-day post-ME time-point. This striking temporal increase in P-CREB level was paralleled by a concomitant increase of two CREB-regulated pro-survival effectors, namely Bcl-2 and Bcl-w. We present our results in the context of recent advances about adult visual neocortex and propose that ME induces a multifaceted CREB-mediated response that favors intrinsic stability of neurons and facilitates mature cortical networks to reorganize over a prolonged period. PMID- 17336090 TI - Molecular reconstitution of functional GABAergic synapses with expression of neuroligin-2 and GABAA receptors. AB - Trans-synaptic cell adhesion molecules neuroligins and neurexins play an important role in promoting central synapse formation. We report here a molecular reconstruction of functional GABAergic synapses in non-neuronal cells with the coexpression of postsynaptic cell adhesion molecule neuroligin-2 (NL-2) and GABA(A) receptors. HEK 293T cells were co-transfected with GABA(A) receptors and NL-2 or its homologue neuroligin-1 (NL-1), and then cocultured with hypothalamic cultures which are enriched with GABAergic neurons. Both spontaneous and action potential-evoked GABAergic events were readily detected in HEK 293T cells coexpressing GABA(A) receptors with NL-2, but not with NL-1. Aggregating NL-2 with specific antibodies in live cells resulted in coaggregation of GABA(A) receptors. Expression of NL-2 in HEK 293T cells also induced stronger GABAergic presynaptic differentiation than that of NL-1 in neuronal cocultures. These results suggest that NL-2 may potentially serve as a central organizer for GABAergic synapse assembly by interacting with both presynaptic neurexins and postsynaptic GABA(A) receptors. PMID- 17336091 TI - Irregular helicoids in leech cocoon membranes. AB - Helicoids in the cocoon membrane of leeches Theromyzon tessulatum and Erpobdella punctata comprise a twisted superposition of layers, each containing a variable number of planes formed by unidirectional fibrils. Straight fibrils intersecting at different angles were displayed in tangential sections through the cocoon wall of each species. When the sectioning angle was below a certain value (i.e., the critical angle), bow-shaped lines apparent in oblique sections were replaced by a succession of layers containing straight fibrils, permitting a direct measurement of step-angle change between successive layers in a helicoid. By this methodology, we determined that no regularities exist in the succession of step angles or in layer thicknesses within the cocoon membranes, but that the distribution of step-angles between layers was unique for each cocoon type. PMID- 17336092 TI - Apposition of silica lamellae during growth of spicules in the demosponge Suberites domuncula: biological/biochemical studies and chemical/biomimetical confirmation. AB - Recently it has been discovered that the formation of the siliceous spicules of Demospongiae proceeds enzymatically (via silicatein) and occurs matrix guided (on galectin strings). In addition, it could be demonstrated that silicatein, if immobilized onto inorganic surfaces, provides the template for the synthesis of biosilica. In order to understand the formation of spicules in the intact organism, detailed studies with primmorphs from Suberites domuncula have been performed. The demosponge spicules are formed from several silica lamellae which are concentrically arranged around the axial canal, harboring the axial filament composed of silicatein. Now we show that the appositional growth of the spicules in radial and longitudinal direction proceeds in the extracellular space along hollow cylinders; their surfaces are formed by silicatein. The extracellularly located spicules are surrounded by sclerocytes which are filled with both electron-dense and electron-poor vesicles; energy dispersive X-ray analysis/scanning electron microscopical studies revealed that the electron-dense vesicles are filled of silicon/silica and therefore termed silicasomes. The release of the content of the silicasomes into the hollow cylinder suggests that the newly formed silica lamella originate there; in addition the data are compatible with the view that the silicatein molecules, attached at the centripetal and centrifugal surfaces, mediate biosilica formation. In a chemical/biomimetical approach silicatein is linked onto the organic material free spicules after their functionalization with aminopropyltriethoxysilane [amino groups]-poly(acetoxime methacrylate) [reactive ester polymer]-N(epsilon) benzyloxycarbonyl L-lysine tert-butyl ester-Ni(II); finally His-tagged silicatein is immobilized. The matrix-bound enzyme synthesized a new biosilica lamella. These bioinspired findings are considered as the basis for a technical use/application/utilization of hollow cylinders formed by matrix-guided silicatein molecules for the biocatalytic synthesis of nanostructured tubes. PMID- 17336093 TI - Groupwise independent component decomposition of EEG data and partial least square analysis. AB - This paper focuses on two methodological developments for analysis of neuroimaging data. The first is the derivation of robust spatiotemporal activity patterns across a group of subjects using a combination of principal component analysis (PCA) and independent component analysis (ICA). In applications to ERP data, the space dimension is typically represented in terms of scalp electrodes. The signal recorded by high density electrode caps is known to be highly correlated due in part to volume conduction. Consequently, this redundancy is also reflected in spatiotemporal patterns characterizing signal differences across experimental conditions. We present an alternative spatial representation and signal compression based on PCA for dimensionality reduction and ICA conducted across all subjects and conditions simultaneously. The second advancement is the use of partial least squares (PLS) analysis to assess task dependent changes in the expression of the independent components. In an application to empirical ERP data, we derive an efficient number of independent component maps. Comparative PLS analysis on the independent components versus original electrode data shows that task effects are not only preserved under compression, but also enhanced statistically. PMID- 17336094 TI - Regulation of anterior insular cortex activity using real-time fMRI. AB - Recent advances in functional magnetic resonance imaging (fMRI) data acquisition and processing techniques have made real-time fMRI (rtfMRI) of localized brain areas feasible, reliable and less susceptible to artefacts. Previous studies have shown that healthy subjects learn to control local brain activity with operant training by using rtfMRI-based neurofeedback. In the present study, we investigated whether healthy subjects could voluntarily gain control over right anterior insular activity. Subjects were provided with continuously updated information of the target ROI's level of activation by visual feedback. All participants were able to successfully regulate BOLD-magnitude in the right anterior insular cortex within three sessions of 4 min each. Training resulted in a significantly increased activation cluster in the anterior portion of the right insula across sessions. An increased activity was also found in the left anterior insula but the percent signal change was lower than in the target ROI. Two different control conditions intended to assess the effects of non-specific feedback and mental imagery demonstrated that the training effect was not due to unspecific activations or non feedback-related cognitive strategies. Both control groups showed no enhanced activation across the sessions, which confirmed our main hypothesis that rtfMRI feedback is area-specific. The increased activity in the right anterior insula during training demonstrates that the effects observed are anatomically specific and self-regulation of right anterior insula only is achievable. This is the first group study investigating the volitional control of emotionally relevant brain region by using rtfMRI training and confirms that self regulation of local brain activity with rtfMRI is possible. PMID- 17336095 TI - Interactive visualization of multiresolution image stacks in 3D. AB - Conventional microscopy, electron microscopy, and imaging techniques such as MRI and PET commonly generate large stacks of images of the sectioned brain. In other domains, such as neurophysiology, variables such as space or time are also varied along a stack axis. Digital image sizes have been progressively increasing and in virtual microscopy, it is now common to work with individual image sizes that are several hundred megapixels and several gigabytes in size. The interactive visualization of these high-resolution, multiresolution images in 2D has been addressed previously [Sullivan, G., and Baker, R., 1994. Efficient quad-tree coding of images and video. IEEE Trans. Image Process. 3 (3), 327-331]. Here, we describe a method for interactive visualization of multiresolution image stacks in 3D. The method, characterized as quad-tree based multiresolution image stack interactive visualization using a texel projection based criterion, relies on accessing and projecting image tiles from multiresolution image stacks in such a way that, from the observer's perspective, image tiles all appear approximately the same size even though they are accessed from different tiers within the images comprising the stack. This method enables efficient navigation of high resolution image stacks. We implement this method in a program called StackVis, which is a Windows-based, interactive 3D multiresolution image stack visualization system written in C++ and using OpenGL. It is freely available at http://brainmaps.org. PMID- 17336096 TI - Specific, selective or preferential: comments on category specificity in neuroimaging. AB - An important goal of functional neuroimaging has been to localize stimulus specific processes in the brain. Numerous studies have revealed particular patterns of brain activity in different cortical areas in response to different object categories such as faces, body parts, places, words, letters and so forth. However, quite different patterns of activation have been given a similar interpretation in terms of category or domain specificity. Other characteristics than the response to the target category have sometimes been used to address whether a cortical brain area is functionally specialized for a given stimulus category, such as automatic processing [e.g. Joseph, J., Cerullo, M., Farley, A., Steinmetz, N., Mier, C., 2006. fMRI correlates of cortical specialization and generalization for letter processing. NeuroImage 32, 806-820] or assemblage [Haxby, J.V., Gobbini, M.I., Furey, M.L., Ishai, A., Schouten, J.L., Pietrini, P., 2001. Distributed and overlapping representations of faces and objects in ventral temporal cortex. Science 293, 2425-2430]. Here we frame the debate around the notions of category specificity as defined by Fodor [Fodor, J., 1983. The modularity of Mind. MIT Press, Cambridge, MA., Fodor, J., 2001. The mind doesn't work that way: the scope and limits of computational psychology "A Bradford book" MIT Press, Cambridge, MA] and argue that brain activation patterns consistent with category specificity remain to be demonstrated. We review possible alternatives and lay out the experimental conditions required for a conclusive demonstration of category-specific specialization in brain imaging studies. PMID- 17336097 TI - Attenuating illusory binding with TMS of the right parietal cortex. AB - A number of neuroimaging and neuropsychology studies have implicated various regions of parietal cortex as playing a critical role in the binding of color and form into conjunctions. The current study investigates the role of two such regions by examining how parietal transcranial magnetic stimulation (TMS) influences binding errors known as 'illusory conjunctions'. Participants made fewer binding errors after 1 Hz rTMS of the right intraparietal sulcus (IPS), while basic perception of features (color and shape) was unaffected. No perceptual effects were found following left IPS stimulation, or stimulation of the right angular gyrus at the junction of the transverse occipital sulcus (IPS/TOS). These results support a role for the parietal cortex in feature binding but in ways that may require rethinking. PMID- 17336098 TI - An optimized in vitro assay for screening compounds that stimulate liver cell glucose utilization with low cytotoxicity. AB - INTRODUCTION: Screening compounds that stimulate liver cell glucose utilization with low cytotoxicity plays an important role in anti-diabetic drug discovery. Existing in vitro assay for the quantitative measurement of cell glucose utilization rate and cytotoxicity of compounds needs to be modified in order to improve the simplicity and reproducibility. An optimized assay was described to addresses these problems. METHODS: Compounds were directly mixed with cell suspension. After 20 h incubation, glucose decrement detection in culture medium was performed, followed by the assessment of cell viability using Cell Counting Kit-8 (CCK-8). RESULTS: A series of experiments were conducted to define optimal conditions such as cell inoculation density, incubation time and CCK-8 concentration in cell culture medium. Glucose utilization unit (GUU) was defined for the evaluation of both efficacy and cytotoxicity of a compound. It was found that Rosiglitazone significantly stimulated cell glucose utilization with negligible cytotoxicity at the concentration of 10(-5) M. CONCLUSION: The simplicity and efficiency of the optimized method has been proven in this study. Our findings show that this assay has potential application in anti-diabetic drug discovery such as new peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. PMID- 17336099 TI - Simultaneous recording of electroencephalogram and blood pressure in conscious telemetered rats during ictal state. AB - INTRODUCTION: Seizures are accompanied by autonomic dysfunction which in turn influences cardiovascular variables. A method for simultaneous acquisition of electroencephalogram (EEG) and arterial blood pressure (BP) during seizures in conscious animals has not previously been described. METHODS: The effect of pentylenetetrazole (PTZ) was first studied on isolated rat atria. EEG and BP were then monitored simultaneously in conscious rats, with a chronically implanted radiotelemetric device. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) during epileptiform seizures induced by intraperitoneal administration of PTZ were monitored to validate the method. RESULTS: PTZ did not have significant inotropic or chronotropic effect in isolated atria. The radiotelemetry system used to acquire data in unrestrained conscious rats enabled us to study neurological excitation (EEG) and cardiovascular variables (BP and HR) during seizures. Our results demonstrated that this method can be used to study the effect of neuronal excitation on cardiovascular variables and vice versa. PMID- 17336100 TI - Different disturbances--one pathway of protein unfolding. Actin folding-unfolding and misfolding. AB - This review summarizes the results of our investigations of actin unfolding refolding and presents the notion that protein unfolding pathway, the number and the appearance order of intermediate states do not dependent on denaturing agents. To place our concept in the context of current knowledge of protein folding, we review in brief the development of general ideas of protein folding mechanisms, paying special attention to some key points of this process. Thus we focus on the characteristics of amino acid sequences that provide the existence of protein native structure, and on the interactions that compensate the increase of free energy due to the decrease of entropy on the way from multitude unfolded conformations to unique native state. In particular, we emphasize that ordered structures can arise both due to intramolecular and intermolecular interactions which lead to the formation of native and misfolded (associates, amorphous aggregates amyloid and amyloid-like fibrils) states, respectively. PMID- 17336101 TI - Definition of a direct extracellular interaction between Met and E-cadherin. AB - High levels of the Met tyrosine kinase receptor expression are associated with metastatic disease. Met activation by hepatocyte growth factor (HGF) is associated with decreased E-cadherin-dependent cell-cell contacts. The molecular mechanism underlying this process remains unclear. To better understand the relationship between E-cadherin and Met, we assessed Met localization in cells which form mature E-cadherin-dependent adhesion HT-29 and cells which have lost E cadherin expression BT-549. Met colocalized with E-cadherin at the site of cell cell adhesion in HT-29 cells, but Met was distributed in an intracellular compartment in BT-549 cells. Forced expression of E-cadherin in BT-549 cells recruited Met to the membrane. Cross-linking studies suggested that Met and E cadherin interact in the extracellular domain in HT-29 cells. This is the first evidence of a physical interaction between Met and E-cadherin. We suggest that this receptor/cadherin pairing may be a mechanism for cellular presentation of receptors in a manner that localizes them optimally for interaction with ligand. PMID- 17336102 TI - Substance P enhances soluble ICAM-1 release from adult rat cardiac fibroblasts by a p42/44 MAPK- and PKC-mediated mechanism. AB - Substance P, a pro-inflammatory neuropeptide, is released from cardiac peptidergic nerves under conditions like ischemia but whether it modulates inflammatory processes in the heart remains unexplored. This study demonstrates for the first time that substance P augments the production of the soluble form of intercellular adhesion molecule-1, sICAM-1, by adult rat cardiac fibroblasts. However, RT-PCR showed no concomitant increase in ICAM-1 transcript levels, suggesting that the increase in sICAM-1 may involve post transcriptional/translational mechanisms. Use of pharmacological inhibitors revealed that the stimulatory effect of substance P on sICAM-1 production is mediated by p42/44 MAPK and protein kinase C. Preliminary experiments also showed that the neuropeptide stimulates the production of prostaglandin E(2) by cardiac fibroblasts. The findings support the postulation that substance P may modulate multiple inflammatory responses within the myocardium through release of pro inflammatory mediators from resident fibroblasts. PMID- 17336103 TI - Extra-cellular matrix proteins induce re-distribution of alpha-actinin-1 and alpha-actinin-4 in A431 cells. AB - Alpha-actinins are actin-binding proteins of non-muscle cells, which can participate in the regulation of transcription factor activity. We describe the distribution of alpha-actinin-1 and -4 depending on different actin cytoskeleton formed as a result of cell adhesion to extracellular matrix proteins, such as fibronectin and laminin 2/4. Immunofluorescent studies show a difference in the distribution of alpha-actinin and -4. Both isoforms localise along stress-fibres, but alpha-actinin-1 localises in the perinuclear region more abundantly than alpha-actinin-4. Western blot analysis demonstrated existence of truncated forms of both isoforms. Truncated alpha-actinin-1 appears in cells spread on fibronectin or laminin. Cell spreading also correlated with more tight association of alpha-actinin-4 with chromatin. Basing on our previous finding of an interaction of alpha-actinin-4 with p65 subunit of the NF-kappaB, we checked the possible influence of immobilised ligands on its redistribution in nuclear complexes containing p65. alpha-Actinin-4 seems to be present in some but not all nuclear complexes containing p65. Immobilised ligands may affect the interaction of alpha-actinin-4/p65 complexes with chromatin. The data suggest that adhesion to extra-cellular matrix may interfere in cellular reactions mediated by alpha actinin-1 and -4. PMID- 17336104 TI - Enhanced neural differentiation of neural stem cells and neurite growth by amniotic epithelial cell co-culture. AB - Amniotic epithelial cells (AECs) were reported to show a neuroprotective effect on neurons, but there was no direct evidence for a functional relationship between neural stem cells (NSCs) and AECs. The aim of this study was to determine whether AECs could stimulate differentiation and expand neurogenesis of NSCs, and whether the roles were due to a diffusible factor or required direct cell-cell contact. AECs were isolated from rat amnion on E14-16 and NSCs were isolated from neocortical tissue. The growth and differentiation of NSCs were compared under different conditions. The results showed that NSCs cultured with FGF-2 proliferated and formed floating neurospheres while those grown in B27 without FGF-2 failed to thrive. Those grown either with AEC conditioned medium or in transwells showed significantly improved survival. Moreover, the neural differentiation and length of neurite were greater in exogenous FGF groups when NSCs were allowed direct contact with AECs. Western blotting, immunocytochemistry and RT-PCR indicated that rat AECs could secrete NT-3 and BDNF. Furthermore, the presence of FGF-2 enhanced the function of AECs. These findings identified that AECs may be regarded as a critical component of NSCs niche and suggested that direct cell-to-cell contact may provide additional and independent support. Such information would circumvent the need for AECs-NSCs co-culture and could potentially facilitate the production of neurons for future clinical applications. PMID- 17336105 TI - Completing the audit cycle: comparison of cardiac risk factor management in patients with intermittent claudication in two time periods. AB - AIM: The first line treatment of patients with intermittent claudication (IC) is to prolong life via cardiac risk factor management. We aimed to compare current standards of secondary prevention with those in a previously published audit. METHODS: Risk factor data was prospectively collated on 304 consecutive new referrals attending the claudication clinic over a 1-year period (2004/2005) and compared to the 104 patients assessed in 2000. RESULTS: In 2004/5 30%, (n=91) of patients did not have a diagnosis of IC confirmed (p<0.01). The use of antiplatelet therapy remained static at 73%. Statin therapy increased in 2004/5 (62% versus 38%, p<0.01) but blood pressure control remained poor with 65% failing to achieve the target levels. Smoking cessation therapy continues to be offered to a minority of patients and 17% of patients have previously undiagnosed diabetes in 2004/2005 (p-value 0.353). The number of patients who have been advised to increase physical activity significantly has fallen from 15% to 2% in the 2004/5 (p<0.01). CONCLUSIONS: Difficulties exist in diagnosing intermittent claudication in primary care and cardiac risk factor management continues to be sub-optimally managed. PMID- 17336106 TI - A short incision for carotid endarterectomy results in decreased morbidity. AB - OBJECTIVES: To investigate the effect of a short incision (<5 cm) on the complication rate of the carotid endarterectomy (CEA). DESIGN: A retrospective cohort study. PATIENTS AND METHODS: From January 1994 to December 2005, 874 patients underwent 1048 primary carotid endarterectomy (CEA) procedures. Seven hundred and sixty nine operations were performed through a long neck incision (group A), while 279 were performed through a smaller incision (<5 cm) according to a standard protocol (group B). Preoperative and postoperative cranial nerve assessment was completed on all patients. The main outcome measures were stroke, death, cranial and cervical nerve injuries rates. RESULTS: The 30-day mortality rate was 0.26% in group A and 0.35% in group B (p=.792). The stroke rate was 0.13% and 0% in group A and B respectively (p=.839). The mean length of stay was 2.59 days in group A and 1.67 days in group B (p<.0001). In group A the overall incidence of motor and sensory nerve deficits was 13.5% (104 CEA, 92 patients) but in group B 2.9% (8 CEA, 7 patients, p<.0001, odds ratio [OR] 0.189, 95% confidence interval [CI] 0.091-0.393). CONCLUSIONS: Carotid endarterectomy through a small incision is a feasible and safe approach that provides cosmetic results and fewer nerve complications without compromising the safety of the procedure. PMID- 17336107 TI - Treatment of chronic mesenteric ischemia by subintimal angioplasty of an occluded superior mesenteric artery. AB - INTRODUCTION: Subintimal angioplasty is an established technique for the recanalisation of occluded vessels. It has been applied extensively to the peripheral arterial system but not the mesenteric vessels in mesenteric angina. REPORT: We report the first described case of recanalisation of a mesenteric vessel. The vessel has remained patent for five years with good symptomatic relief. DISCUSSION: Subintimal angioplasty could represent an alternative treatment to major surgery for occlusive disease of the mesenteric vessels. PMID- 17336108 TI - Kinetics of RANKL, RANK and OPG expressions in experimentally induced rat periapical lesions. AB - OBJECTIVE: The object of this study was to elucidate the kinetics of receptor activator of NFkB ligand (RANKL), RANK, osteoprotegerin (OPG), and cytokine expressions in experimentally induced rat periapical lesions. STUDY DESIGN: The mRNA expressions of RANKL, RANK, OPG, and cytokines in experimentally induced rat periapical lesions were evaluated by real-time PCR. The lesions were induced in male Wistar rats (n = 48, 5 weeks of age) by unsealed pulp exposure of the lower first molars. RESULTS: Expression of RANKL was up-regulated at the beginning of lesion expansion, and expression ratio of RANKL against OPG, a competitor of RANKL, peaked at 2 and 3 weeks. Expression of inflammatory cytokines, such as TNF alpha, IL-1alpha, and IL-1beta also increased at this stage, suggesting contribution of synergic effects of RANKL and proinflammatory cytokine signaling to lesion expansion. Most of RANKL+ cells were fibroblastic, but few of them were T cells. CONCLUSION: Expression of RANKL and proinflammatory cytokines was correlated with periapical lesion expansion. PMID- 17336109 TI - Salivary gland development. AB - Salivary glands provide an excellent model for the study of epithelial mesenchymal interactions and branching morphogenesis. This review will discuss the anatomy of different types of glands, in a range of different organisms. Then, concentrating on the mouse submandibular gland, the stages of salivary gland development will be reviewed and the relative role of the mesenchyme and the epithelium will be discussed. Finally, the genes thought to play a role in development of the glands from initiation to differentiation will be reviewed. PMID- 17336110 TI - Severe chemosis caused by nephrotic syndrome in a goat: a case report. AB - A 3-year old female goat with nephrotic syndrome was presented because of severe bilateral chemosis. The diagnosis was based on clinical findings, decreased packed cell volume, increased serum urea and creatinine, decreased serum protein and protein loss via the urinary tract. At post mortem examination, a chronic glomerulonephritis and interstitial nephritis were found. In addition to severe conjunctival oedema, ascites and subcutaneous oedema in the region of the larynx were noted. Immunohistochemistry for the detection of chlamydial antigen in the conjunctiva was negative. This is the first report of severe chemosis caused by nephrotic syndrome in a goat. PMID- 17336111 TI - Immunohistochemical expression of TopBP1 in feline mammary neoplasia in relation to histological grade, Ki67, ERalpha and p53. AB - The immunohistochemical expression of topoisomerase IIbeta binding protein 1 (TopBP1) was examined in 123 feline mammary lesions (18 non-neoplastic lesions including six fibroadenomatous hyperplasia and 12 duct ectasia, 17 adenomas and 88 carcinomas) in relation to histological grade, oestrogen receptor alpha (ERalpha) status, proliferation index (Ki67) and p53 expression. There was positive staining for TopBP1 in 122 of 123 feline mammary lesions, although nine samples had fewer than 20% positive cells. The percentage of cells positive for TopBP1 increased with histological grade. Most staining was nuclear but both nuclear and cytoplasmic staining was observed as the degree of malignancy increased. TopBP1 is expressed in feline mammary tumours and its expression is correlated with histological grade. Many neoplasms which over-express p53 or are ERalpha negative show TopBP1 immunoreactivity. PMID- 17336112 TI - Relaxation of protons by radicals in rotationally immobilized proteins. AB - Proton spin-lattice relaxation by paramagnetic centers may be dramatically enhanced if the paramagnetic center is rotationally immobilized in the magnetic field. The details of the relaxation mechanism are different from those appropriate to solutions of paramagnetic relaxation agents. We report here large enhancements in the proton spin-lattice relaxation rate constants associated with organic radicals when the radical system is rigidly connected with a rotationally immobilized macromolecular matrix such as a dry protein or a cross-linked protein gel. The paramagnetic contribution to the protein-proton population is direct and distributed internally among the protein protons by efficient spin diffusion. In the case of a cross-linked-protein gel, the paramagnetic effects are carried to the water spins indirectly by chemical exchange mechanisms involving water molecule exchange with rare long-lived water molecule binding sites on the immobilized protein and proton exchange. The dramatic increase in the efficiency of spin relaxation by organic radicals compared with metal systems at low magnetic field strengths results because the electron relaxation time of the radical is orders of magnitude larger than that for metal systems. This gain in relaxation efficiency provides completely new opportunities for the design of spin-lattice relaxation based contrast agents in magnetic imaging and also provides new ways to examine intramolecular protein dynamics. PMID- 17336113 TI - Variation of steroid concentrations during the reproductive cycle of the clam Ruditapes decussatus: a one year study in the gulf of Gabes area. AB - Progesterone, testosterone and estradiol-17beta were measured by radio immunoassay (RIA) in the gonads of the clam Ruditapes decussatus. The reproductive cycle was also investigated. Our study covered a period of one year, from September 2003 to August 2004. The chosen site "Kerkennah", located out of industrial effluents, belongs to the gulf of Gabes area (Tunisia). Steroids varied from 178 to 2459 pg g(-1) wet mass for progesterone, from 40 to 326 pg g( 1) wet mass for testosterone and from 10 to 235 pg g(-1) wet mass for estradiol 17beta in females. However in males, these steroids ranged from 304 to 2303 pg g( 1) wet mass for progesterone, from 81 to 381 pg g(-1) wet mass for testosterone and from 48 to 168 pg g(-1) wet mass for estradiol-17beta. The reproductive cycle of R. decussatus, investigated by histological examination of gonadic sections, showed that gametogenesis occurred from April to February in males and from April to November in females. Progesterone and testosterone increased at the end of gametogenesis in both sexes. The highest estradiol-17beta was recorded at the beginning of vitellogenesis in females. Fluctuations in the levels of sex steroids during the reproductive cycle suggest their possible role as endogenous modulators of gametogenesis in R. decussatus. Although this species is considered as gonochoristic, 0.83% of hermaphrodites were observed. PMID- 17336114 TI - A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal. AB - Guanidinoacetate methyltransferase (GAMT) deficiency (MIM 601240), an autosomal recessive disorder of creatine biosynthesis, presents with mental retardation, extrapyramidal symptoms, autistic-like behavior and epilepsy. Other hallmarks are cerebral creatine deficiency, increased levels of guanidinoacetate in body fluids and mutations in the GAMT gene. Creatine supplementation partially restores cerebral creatine content. Worldwide, 29 patients have been identified and 15 different mutations have been reported in the GAMT gene. Ten out of these 29 patients are of Portuguese origin. Likely, a founder effect and a high carrier rate in Portugal exist, since in 17 out of the 20 Portuguese alleles the c.59G>C; p.Trp20Ser mutation was found. We investigated the carrier rate of the c.59G>C; p.Trp20Ser mutation in different regions of Portugal and confirmed the pathogenic nature of this missense mutation by transient transfections. Anonymous bloodspots (1002) were screened for the presence of the c.59G>C; p.Trp20Ser mutation by SNaPshot (Single Nucleotide Polymorphism Multiplex Kit). Eight carriers of c.59G>C; p.Trp20Ser were detected of which four are derived from the Archipelagos. This suggests that the carrier rate of the c.59G>C; p.Trp20Ser mutation is relatively high in these islands, as well as in other parts of Portugal. It also implies that newborn screening in these regions is warranted for this treatable disorder. PMID- 17336115 TI - Systems analysis of energy metabolism elucidates the affected respiratory chain complex in Leigh's syndrome. AB - Leigh's syndrome is a complex neurological disease with little known correlation between causes and symptoms. Mutations in pyruvate dehydrogenase and electron transport chain complexes have been associated with this syndrome, although the identification of affected enzymes is difficult, if not impossible, with non invasive clinical tests. In this study, isotopomer analysis is used to characterize the metabolic phenotype of normal and Leigh's syndrome fibroblasts (GM01503), thereby identifying affected enzymes in the diseased cells. Fibroblasts are grown with DMEM media enriched with (13)C labeled glucose. Amino acids from media and proteins as well as lactate are analyzed with GC-MS to identify their label distributions. A computational model accounting for all major pathways in fibroblast metabolism (including 430 metabolites and 508 reactions) is built to determine the metabolic steady states of the normal and Leigh's cell lines based on measured substrate uptake and secretion rates and isotopomer data. Results show that (i) Leigh's syndrome affected cells have slower metabolism than control fibroblasts as evidenced by their overall slower substrate utilization and lower secretion of end products; (ii) intracellular fluxes predicted by the models, some of which are validated by biochemical studies published in the literature, show that the respiratory chain in Leigh's affected cells can produce ATP at a similar rate as the controls, but with a more restricted flux range; and (iii) mutations causing the defects observed in the Leigh's cells are likely to be in succinate cytochrome c reductase. PMID- 17336117 TI - Recurrent catheter-related bloodstream infections: risk factors and outcome. PMID- 17336116 TI - Safety of intracerebroventricular copper histidine in adult rats. AB - Classical Menkes disease is an X-linked recessive neurodegenerative disorder caused by mutations in a P-type ATPase (ATP7A) that normally delivers copper to the developing central nervous system. Infants with large deletions, or other mutations in ATP7A that incapacitate copper transport to the brain, show poor clinical outcomes and subnormal brain copper despite early subcutaneous copper histidine (CuHis) injections. These findings suggest a need for direct central nervous system approaches in such patients. To begin to evaluate an aggressive but potentially useful new strategy for metabolic improvement of this disorder, we studied the acute and chronic effects of CuHis administered by intracerebroventricular (ICV) injection in healthy adult rats. Magnetic resonance imaging (MRI) after ICV CuHis showed diffuse T(1)-signal enhancement, indicating wide brain distribution of copper after ICV administration, and implying the utility of this paramagnetic metal as a MRI contrast agent. The maximum tolerated dose (MTD) of CuHis, defined as the highest dose that did not induce overt toxicity, growth retardation, or reduce lifespan, was 0.5mcg. Animals receiving multiple infusions of this MTD showed increased brain copper concentrations, but no significant differences in activity, behavior, and somatic growth, or brain histology compared to saline-injected controls. Based on estimates of the brain copper deficit in Menkes disease patients, CuHis doses 10-fold lower than the MTD found in this study may restore proper brain copper concentration. Our results suggest that ICV CuHis administration have potential as a novel treatment approach in Menkes disease infants with severe mutations. Future trials of direct CNS copper administration in mouse models of Menkes disease will be informative. PMID- 17336118 TI - Ageing and blood pressure modulate the relationship between metabolic syndrome and aortic stiffness in never-treated essential hypertensive patients. A comparative study. AB - OBJECTIVE: The aim of this study was to evaluate the impact of the metabolic syndrome (MS) and its components as defined by the National Cholesterol Education Program Adult Treatment Panel III on arterial stiffness in untreated hypertensive patients. METHODS: This was a cross sectional multi-center study performed in 46 healthcare centers, from 14 countries involved in the Complior study. Four hundred and forty patients (55% male) aged 18-73 years, with untreated essential hypertension were selected at inclusion. All patients underwent a full evaluation for all the risk factors representing the MS and an assessment of arterial stiffness using automatic measurement of carotid-femoral pulse wave velocity (PWV). RESULTS: In the overall population significant correlations were found, respectively, between PWV, MS (R=0.2, P<0.001) and gender (R=0.11, P=0.023) where PWV was higher in women. After adjustment for age and systolic blood pressure (SBP), analysis of covariance showed an independent effect of the MS on PWV, this effect increased with ageing and SBP especially after 47 years (age median, P=0.0047). Moreover, increase of mean PWV was highly associated with the number of MS factors in global population (P<0.001). These findings suggest that MS leads to early arterial wall ageing. CONCLUSIONS: Presence of MS induces an increase of arterial stiffness in untreated hypertensive patients independently from age and SBP. The increase of PWV is proportional to number of risk factors and affects principally patients after mid-age of 47 years where MS has ageing effects on arterial stiffness. PMID- 17336119 TI - Chagas' disease: facts and reality. PMID- 17336120 TI - Relationship between Helicobacter pylori virulence factors and regulatory cytokines as predictors of clinical outcome. AB - Helicobacter pylori infection is highly prevalent in Chile (73%). Usually a minority of infected patients develops complications such as ulcers and gastric cancer that have been associated with the presence of virulence factors (cagA, vacA) and host T helper response (Th1/Th2). Our aim was to evaluate the relationship between strain virulence and host immune response, using a multiple regression approach for the development of a model based on data collected from H. pylori infected patients in Chile. We analyzed levels of selected cytokines determined by ELISA (interleukin (IL)-12, IL-10, interferon (IFN)-gamma and IL-4) and the presence of cagA and vacA alleles polymorphisms determined by PCR in antral biopsies of 41 patients referred to endoscopy. By multiple regression analysis we established a correlation between bacterial and host factors using clinical outcome (gastritis and duodenal ulcer) as dependent variables. The selected model was described by: clinical outcome=0.867491 (cagA)+0.0131847 (IL 12/IL-10)+0.0103503 (IFN-gamma/IL-4) and it was able to explain over 90% of clinical outcomes observations (R(2)=96.4). This model considers that clinical outcomes are better explained by the interaction of host immune factors and strain virulence as a complex and interdependent mechanism. PMID- 17336121 TI - Cerebral vasculitis in a patient with rheumatoid arthritis. AB - Inflammatory vasculitis of the central nervous system is exceedingly rare in patients with rheumatoid arthritis (RA). The symptoms may be misleading. Most of the reported cases occurred in males with long-standing, nodular, destructive, rheumatoid factor-positive disease. Severe constitutional symptoms and prominent extraarticular manifestations of vasculitis were usually present. We report a case of cerebral vasculitis in a 59-year-old woman with a 20-year history of destructive rheumatoid factor-positive RA that was well controlled by methotrexate. Headache that was unresponsive to symptomatic treatment developed abruptly, together with gait disorders. Magnetic resonance imaging of the brain showed dot-like areas of high-signal in a periventricular subcortical distribution on both sides. Magnetic resonance angiography visualized a long tight stenosis of the right internal carotid artery and a string-of-beads stenosis of the left internal carotid artery suggesting vasculitis. Pulse therapy with methylprednisolone (1 g/d for 3 days) and cyclophosphamide (1 g) once a month ensured resolution of the neurological symptoms and laboratory evidence of inflammation. There was no evidence of a relapse at last follow-up after 5 months. Cerebral vasculitis is usually treated with monthly glucocorticoid and cyclophosphamide boluses separated by continuous glucocorticoid therapy. TNFalpha antagonists may be effective in patients who fail to respond to conventional treatment. However, other vasculitides such as giant cell arteritis and Wegener's granulomatosis must be ruled out, as they are refractory to TNFalpha antagonist therapy. PMID- 17336122 TI - Bilateral elastofibroma dorsi. AB - Elastofibromas (EFD) are rare benign soft tissue tumors that are almost always located at the inferior pole of the scapula, deep to the serratus anterior muscle. They are more frequent in elderly women. Their anatomical location and a distinctive clinical symptom distinguish them from malignant soft tissue tumours. They can usually be diagnosed on the basis of their imaging characteristics. Despite their low incidence, these lesions should be kept in mind to differentiate them from malignant tumours and to avoid unnecessary biopsies and wide or radical surgery. We present the case of a 55-year-old woman who complained of chronic pain related to a right infrascapular mass. She was diagnosed by magnetic resonance imaging (MRI) of bilateral subescapular tumor masses both compatible with elastofibroma. She underwent resection of the symptomatic right lesion through an amyotomical approach. PMID- 17336123 TI - Practice patterns in outpatient rheumatology: a pilot evaluation of medical file content. AB - OBJECTIVES: High-quality medical records that contain detailed data on the patient and disease are essential to high-quality patient care. RHEVER is a network of hospital- and office-based rheumatologists created in 1999 to pursue a number of objectives, including the development of recommendations about items that should be recorded routinely at each patient visit. Subsequently, one of the RHEVER members investigated whether these recommendations were followed by RHEVER participants at a teaching hospital. METHODS: A cross-section of paper-based outpatient files at the rheumatology clinic of the Cochin Teaching Hospital, Paris, France, was studied. The sample comprised 50 files taken at random and 30 files of patients with rheumatoid arthritis. RESULTS: In the 50 unselected files, the reason for the visit was consistently provided, but the diagnosis was variably recorded and decisions about investigations and treatments were not always described. Of the 30 files in patients with rheumatoid arthritis, 75% contained the full set of recommended clinical items. CONCLUSION: This pilot study establishes the feasibility of practice pattern evaluation by rheumatologists. A similar study should be conducted among office-based RHEVER participants. Follow-up investigations are needed to evaluate the impact of medical record evaluations on quality of care. PMID- 17336124 TI - Hypoparathyroidism in systemic lupus erythematosus. AB - Hypoparathyroidism is a rare disease. The main cause of hypoparathyroidism is postsurgical hypoparathyroidism. However, cases of hypoparathyroidism in patients suffering from SLE exist although it is uncommon. Only three previous cases have been reported. We present the case of a woman suffering both from systemic lupus erythematosus and hypoparathyroidism. This reported association of hypoparathyroidism with lupus expands the spectrum of endocrine disorders seen in this disease. We suggest that there may be a common underlying pathophysiological process linking these diseases. PMID- 17336125 TI - [Evaluation of treatment relating to gestational trophoblastic tumor registered to the French Trophoblastic Disease Reference Center (TDRC) in Lyon from 1999 to 2005]. AB - OBJECTIVES: The aim of this study was both to analyse if gestational trophoblastic neoplasia (GTN) registered to the French Trophoblastic Disease Reference Center (TDRC) in Lyon (France) were managed according to the FIGO criteria for diagnosis of GTN and if chemotherapy was adapted to the 2000 FIGO prognostic scoring system. PATIENTS AND METHODS: Retrospective, descriptive analysis of 167 GTN registered to GTC of Lyon between 1999 and 2005. RESULTS: On the one hand, 66% of women (104/158) had a diagnosis of GTN according to FIGO criteria. One third (n=54) of the patients therefore had a premature or erroneous diagnosis of a tumor, when the treatment started. No supporting element of this premature diagnosis has been found out for 26 patients. The identification of lung and vaginal metastasis and histological diagnosis of invasive mole appeared as the most mentioned inappropriate criteria for diagnosis. On the other hand, chemotherapy was adapted to 2000 FIGO scoring in 91, 5% of cases. Twelve low risk GTN were treated with polychemotherapy and two high risk GTN were treated with monochemotherapy. Moreover 29% of the patients received a non adequate treatment due to deviations from the recommended protocol. DISCUSSION AND CONCLUSION: Non respect of FIGO criteria for the diagnosis of GTN can lead to erroneous diagnosis of tumors. Identification of lung or vaginal metastasis or diagnosis of invasive mole should not automatically justify the diagnosis of gestational trophoblastic neoplasia if the decrease in HCG occurs properly. Respect of FIGO criteria for the diagnosis of GTN and adaptation of chemotherapy to 2000 FIGO scoring are necessary to avoid inadequate treatment of gestational trophoblastic neoplasia. PMID- 17336126 TI - [Another view of maternal mortality in France]. PMID- 17336127 TI - [Vasa previa: one case]. AB - Vasa previa is a rare condition (1/2000 to 1/5000) in which the rupture of membranes may result in fetal haemorrhage (Benckiser's haemorrhage). We report one unusual case of delayed Benckiser's haemorrhage 12 hours after rupture of membranes. We point out the risk situations in which prenatal diagnosis should particularly be sought: low-lying placenta at routine second trimester ultrasound screening, bilobate or succenturiate placenta, velamentous insertion of the umbilical cord, in vitro fertilization. A universal screening, as proposed by certain authors, is also discussed. PMID- 17336128 TI - [Intravascular leiomyomatosis: an original tumor]. AB - An unusual uterus benign tumor, intravascular leiomyomatosis is also a differential diagnosis of uterine fibromas. It is most likely to be diagnosed post operatively and must be treated in an adequate way to avoid a recidive. PMID- 17336129 TI - [Natural cycle in vitro fertilization cycle in poor responders]. AB - Since the beginning of IVF, natural cycle In Vitro Fertilization (NC-IVF) has been largely replaced by IVF with ovarian stimulation. However, natural cycle IVF has several advantages: low cost, no risk of ovarian hyper stimulation syndrome, very low risk of multiple pregnancy. Nevertheless, natural cycle IVF is less effective with a high risk of cancellation due to premature rise of LH, and an increased risk of failed oocyte retrieval. Using GnRH antagonists in a modified natural cycle decreases the occurrence of a premature LH rise. In the context of a poor responder patient, natural IVF could theoretically yield a better quality oocyte coming from a naturally selected follicle and allow a transfer on an endometrium whose receptivity has not been distorted by controlled ovarian stimulation. However, the real place for it has yet to be defined as we lack published data. Only one randomised controlled study in poor responders showed a similar pregnancy rate to a standard protocol representing a cost-effective alternative. Available retrospective data seem to show the same trend especially in the sub group of younger patients (below 38). Natural cycle IVF is a low-risk, low-cost procedure whose interesting results should be further confirmed by large scale prospective studies. PMID- 17336130 TI - Enhancement of sonochemical reaction of terephthalate ion by superposition of ultrasonic fields of various frequencies. AB - The ultrasonic reactor with dual frequency was used and the effect of frequency on the fluorescence intensity of terephthalate ion was experimentally investigated in the frequency range from 176 to 635 kHz. The sonochemical reaction fields were visualized by using sonochemical luminescence of luminol solution. Compared with the fluorescence intensity of terephthalate ion for single frequency, the fluorescence intensity for dual frequency increased. The fluorescence intensity ratio of dual frequency to single frequency had maximum value when the frequency of transducer attached at the bottom wall was comparable in magnitude to that at the side wall. In the case of dual frequency, the sonochemical reaction fields became more extensive in the reactor and more intensive around the center of the reactor. PMID- 17336131 TI - Transcriptional regulation by C-terminal binding proteins. AB - C-terminal binding protein family members function predominantly as transcriptional corepressors in association with sequence specific DNA-binding transcriptional repressors. The vertebrates have two CtBP genes while the invertebrates contain a single gene. Genetic studies indicate that the CtBP genes play pivotal roles in animal development. The vertebrate C-terminal binding proteins (CtBP1 and CtBP2) are highly related and are functionally redundant for certain developmental processes and non-redundant for others. The animal C terminal binding proteins exhibit structural and functional similarity to d isomer-specific 2-hydroxy acid dehydrogenases (D2-HDH). They function as dimers, recruiting transcriptional regulators through two protein-binding interfaces in each monomer. The corepressor complex of CtBP1 contains enzymatic constituents that mediate coordinated histone modification by deacetylation and methylation of histone H3-Lysine 9 and demethylation of histone H3-Lysine 4. CtBP also recruits the small ubiquitin-related modifier (SUMO) conjugating E2 enzyme UBC9 and a SUMO E3 ligase (HPC2), suggesting that CtBP-mediated transcriptional regulation may also involve SUMOylation of transcription factors. In addition to gene-specific transcriptional repression, CtBP1 appears to antagonize the activity of the global transcriptional coactivators, p300/CBP. Genetic evidence also suggests that the fly CtBP (dCtBP) and the vertebrate CtBP2 might activate transcription in a context-dependent manner. The transcriptional regulatory activity of CtBP is modulated by the nuclear NADH/NAD+ ratio and hence appears to be influenced by the metabolic status of the cell. The nuclear dinucleotide ratio may differentially influence the repression activities of factors that recruit CtBP through PLDLS-like motifs and those through non-PLDLS-motifs. PMID- 17336132 TI - SLAM and CD31: signaling molecules involved in cytokine secretion during the development of innate and adaptive immune responses. AB - Immune cells are modulated through the crosslinking of receptors named "immunoreceptors". Ligation of immunoreceptors by their ligands induces a tyrosine-phosphorylation signal that is essential for cell activation or inhibition. Physiologically, immunoreceptor triggering is not enough for cell activation, and stimulation of co-receptors is necessary for antigen-evoked cytokine production. Thus, signal transduction pathways mediated by proteins that regulate cytokine secretion are critical to achieve an effective immune response of the host, where the balance between positive and negative signaling allows effective immune responses, preventing tolerance and autoimmunity. This review deals with recent studies based on the role of the receptor signaling lymphocytic activation molecule (SLAM), a signaling protein that modulates cytokine secretion by immune cells, and the transmembrane glycoprotein CD31, which plays multiple roles in cellular signaling events by modulating the balance between inhibitory and stimulatory signals to immune cells. Recent studies have shed light on the ability of these molecules to transmit different signals that regulate the ability of innate and adaptive immune cells to synthesize stimulatory and inhibitory cytokines. PMID- 17336134 TI - Photophysical investigations on non-covalently linked fullerene/tetraarylporphyrin supramolecular complexes. AB - The host-guest interactions of various tetraarylporphyrins (TP), viz., 5,10,15,20 tetraphenyl-21H,23H-porphyrin (1), 5,10,15,20-tetrakis(octadecyloxyphenyl) 21H,23H-porphyrin (2) and 5,10,15,20-tetrakis(dodecyloxyphenyl)-21H,23H-porphyrin (3) with C60 and C70 have been studied by 1H NMR, UV-vis and fluorescence spectroscopic techniques in toluene medium. All the fullerene/porphyrin complexes are found to be stable with 1:1 stoichiometry. Binding constants (K) of all the fullerene/porphyrin complexes have been determined by fluorescence quenching experiment. The trend in K values revealed that the presence of long chain n alkyl group in tetraarylporphyrin effectively and remarkably increases the selectivity ratio of C70 over C60. Theoretical calculations have extended a good support in interpreting the stability difference between various fullerene/TP complexes. PMID- 17336133 TI - An atlas-based method to compensate for brain shift: preliminary results. AB - Compensating for intraoperative brain shift using computational models has shown promising results. Since computational time is an important factor during neurosurgery, a priori knowledge of the possible sources of deformation can increase the accuracy of model-updated image-guided systems. In this paper, a strategy to compensate for distributed loading conditions in the brain such as brain sag, volume changes due to drug reactions, and brain swelling due to edema is presented. An atlas of model deformations based on these complex loading conditions is computed preoperatively and used with a constrained linear inverse model to predict the intraoperative distributed brain shift. This relatively simple inverse finite-element approach is investigated within the context of a series of phantom experiments, two in vivo cases, and a simulation study. Preliminary results indicate that the approach recaptured on average 93% of surface shift for the simulation, phantom, and in vivo experiments. With respect to subsurface shift, comparisons were only made with simulation and phantom experiments and demonstrated an ability to recapture 85% of the shift. This translates to a remaining surface and subsurface shift error of 0.7+/-0.3 mm, and 1.0+/-0.4 mm, respectively, for deformations on the order of 1cm. PMID- 17336135 TI - Isosbestic-like point in the polarized reflectance spectra of monoclinic crystals -A quantitative approach. AB - If two overlapping bands originate from transition moments that are perpendicular and lie along the principal axes of the infinity frequency dielectric tensor, an isosbestic-like point (ILP) appears in the overlaid polarized IR reflectance spectra of single crystals. These conditions can also be met in principle in case of the reflectance from the ac-plane of a monoclinic crystal despite of the crystal's low symmetry. In order to determine the transition moment directions, diagonalization of the infinity frequency dielectric tensor should be performed. It is shown that a critical magnitude for the appearance of ILP is the angle of incidence. An increase of this angle leads to a transformation of the ILP to an isosbestic-like region, which eventually vanishes at higher incidence angles. Polarized reflectance spectra of gypsum (CaSO4.2H2O), recorded from the ac crystal face, were used to verify the theoretical results. PMID- 17336136 TI - Simple, sensitive, selective and validated spectrophotometric methods for the estimation of a biomarker trigonelline from polyherbal gels. AB - Simple, accurate, reproducible, selective, sensitive and cost effective UV spectrophotometric methods were developed and validated for the estimation of trigonelline in bulk and pharmaceutical formulations. Trigonelline was estimated at 265 nm in deionised water and at 264 nm in phosphate buffer (pH 4.5). Beer's law was obeyed in the concentration ranges of 1-20microg mL(-1) (r2=0.9999) in deionised water and 1-24 microg mL(-1) (r2=0.9999) in the phosphate buffer medium. The apparent molar absorptivity and Sandell's sensitivity coefficient were found to be 4.04 x 10(3)L mol(-1)cm(-1) and 0.0422 microg cm(-2)/0.001A in deionised water; and 3.05 x 10(3)L mol(-1)cm(-1) and 0.0567 microg cm(-2)/0.001A in phosphate buffer media, respectively. These methods were tested and validated for various parameters according to ICH guidelines. The detection and quantitation limits were found to be 0.12 and 0.37 microg mL(-1) in deionised water and 0.13 and 0.40 microg mL(-1) in phosphate buffer medium, respectively. The proposed methods were successfully applied for the determination of trigonelline in pharmaceutical formulations (vaginal tablets and bioadhesive vaginal gels). The results demonstrated that the procedure is accurate, precise, specific and reproducible (percent relative standard deviation <2%), while being simple and less time consuming and hence can be suitably applied for the estimation of trigonelline in different dosage forms and dissolution studies. PMID- 17336137 TI - Theoretical study of the structures and vibrational spectra of the hydrogen bonded systems of 4-cyanophenol with N-bases. AB - The structural and vibrational features of the hydrogen bonded complexes of 1,5,7 triazabicyclo [4.4.0] dec-5-ene (TBD) with one and two 4-CNPhOH molecules have been studied extensively by ab initio SCF/6-31G(d,p) and BLYP calculations with various basis sets: 6-31G(d,p), 6-31+G(d,p) and 6-31++G(d,p). Full geometry optimization was made for the complexes studied. The nature of the hydrogen bonding and the influence of the hydrogen bonding on the structural and vibrational characteristics of the monomers have been investigated. The corrected values of the dissociation energy for the hydrogen-bonded complexes have been calculated in order to estimate their stability. The calculated values of the dissociation energy per phenol molecule indicate that the complex: TBD: 4-CNPhOH (1:1) is more stable than the complex: TBD: 4-CNPhOH (1:2). The changes in the structural and vibrational characteristics upon hydrogen bonding depend on the strength of the hydrogen bonds. In agreement with the experiment, the calculations show that the complexation between TBD and 4-CNPhOH leads to considerably changes in the vibrational characteristics of the stretching O-H vibration. The vibrational frequency of the O-H stretching vibration is shifted to lower wave numbers upon hydrogen bonding. The predicted frequency shifts Deltanu(O-H) for the complexes--TBD: 4-CNPhOH (1:1) and TBD: 4-CNPhOH (1:2) are in the range from -190 cm(-1) to -586 cm(-1). In the same time the IR intensity of the O-H stretching vibration increases dramatically in the hydrogen-bonded complexes. PMID- 17336138 TI - Laser induced amplified spontaneous emission from the B2Pi, L2Pi, and I2Sigma+ valence states of NO. AB - Amplified spontaneous emission (ASE) from single rovibrational levels of valence (non-Rydberg) states of NO molecules has been investigated. The B2Pi (v=24 and 25), L2Pi (v=5 and 6), and I2Sigma+ (v=6) levels have been populated through laser optical-optical double resonance excitation via the Rydberg A2Sigma+ state. Term values for the 2Pi states have been determined with an accuracy of +/-0.03 cm(-1). Analyses of rotationally resolved dispersed ASE spectra in the near infrared region have shown that all the lower states belonged to the Rydberg states. The valence approximately Rydberg coupling in the upper manifolds has driven ASE systems from the valence to the Rydberg levels where they benefit from the strong intensities of inter-Rydberg transitions with Deltav=0. The experimentally predicted valence approximately Rydberg interactions have been compared with theoretical treatments. PMID- 17336139 TI - Vibrational analysis of complexes of urate with IA group metal cations (Li+, Na+ and K+). AB - Vibrational frequency analysis was performed for the complexes of alkali metal cations (Li+, Na+ and K+) with urate in the gas phase. The geometries of all possible metal cation-urate complexes were optimized at the B3LYP/6-311++G(d,p) level. The most stable complex corresponding to the each cation was used for the vibrational frequency analysis including the computation of % potential energy distribution (%PED). For comparison, the vibrational frequency analysis was also performed for the uric acid. The computed results are discussed in terms of the available experimental data. It was revealed that the characteristic stretching vibrational modes corresponding to the metal cation and the interacting nucleophilic sites of urate can be used to identify metals involved in the stone formation in the living system. Changes in different vibrational frequencies of uric acid consequent to the metal cation interactions are discussed. PMID- 17336140 TI - Hartree-Fock, Moller-Plesset calculations and dynamic NMR study of 3,3-dimethoxy 1-(imidazolidin-2-ylidene)propan-2-one. AB - The experimental (1)H, (13)C NMR spectra of 3,3-dimethoxy-1-(imidazolidin-2 ylidene)propan-2-one were recorded in CDCl(3) at temperature range 213-323 K. The variable temperature spectra revealed a dynamic NMR effect which is attributed to restricted rotation around the C=C double bond. Fast exchange processes of deuterium atoms between CDCl(3) and 3,3-dimethoxy-1-(imidazolidin-2 ylidene)propan-2-one or fast exchange of proton between nitrogen and oxygen atoms of carbonyl group is also revealed by broadening of N-H (singlet) proton NMR signals. Proton and carbon theoretical chemical shifts of the title molecule were calculated by using RHF and MP2-GIAO levels and different basis sets in gas phase at 298 K. The calculated proton chemical shifts show that the experimental values have no agreement with theoretical values, but for carbon chemical shifts a good agreement achieved by using RHF with 6-31G basis set and MP2/3-21G, 6-31G basis sets. Discrepancies are attributed to either the limitations of calculating program, because the change of the structure while rotation are not considered. The results showed that to select of basis set has more important rule, because RHF-GIAO level calculation with 6-31G basis set in gas phase can excellently reproduce the (13)C NMR spectrum. Moreover, MP2/3-21G, 6-31G calculation has not significant influence on (13)C NMR chemical shifts with respect to RHF-6-31G. PMID- 17336141 TI - Evaluation of the use of an integrated drug information system by primary care physicians for vulnerable population. AB - OBJECTIVE: To investigate whether an electronic prescribing and integrated drug information system was more likely to be used by primary care physicians for patients of low socioeconomic (SES) patients. METHODS: Prospective 9 months follow-up study was conducted in Montreal, Canada from March to November 2003. The study included 28 primary care physicians and their 4096 respective patients with provincial drug insurance. Utilization rate was defined as the number of times the electronic medication history (EMH) and electronic prescribing system (E-rx) were accessed divided by the total number of medical visits made by those patients. System audit trails (utilization), provincial health insurance databases (visits) were used to measure system utilization rate. For each patient neighborhood-based measures of household income, derived from Statistics Canada, were used to measure socioeconomic status. RESULTS: The EMH was used 14.5 times per 100 visits. In comparison to high SES patients, there was a significant 70% increase (RR: 1.70; 95%CI: 1.15-2.47) in the EMH utilization for low SES patients. The electronic prescribing system was used 38.5 times per 100 visits and did not vary by patient SES. The EMH utilization rate for low SES patients with multiple emergency room (ER) visits was 2.4 times higher than for high SES patients with <1 ER visit (RR: 2.38; 95%CI: 1.36-4.14). The utilization rate for low SES patients, who took, at least six drugs per day, was four times higher compared to high SES patients with less complex drug management (RR: 4.00; 95%CI: 2.22-7.17). CONCLUSIONS: Primary care physicians were more likely to access electronic information on current drug use for patients of low SES taking multiple medications and with fragmented care. PMID- 17336142 TI - An integrated approach to distance learning with digital video in the French speaking Virtual Medical University. AB - The aim of the French-speaking Virtual Medical University project (UMVF) is to share common resources and specific tools in order to improve medical training. Digital video on IP is an attractive tool for higher education but there are a number of obstacles to widespread implementation. This paper describes the UMVF approach to integrating digital video technologies and services in educational projects. PMID- 17336143 TI - Human bocavirus in Italian patients with respiratory diseases. AB - BACKGROUND: hBoV, a recently discovered parvovirus, can be present in the respiratory tract of patients with acute respiratory diseases (ARD), but its etiologic involvement in the underlying diseases is still uncertain. OBJECTIVE: To determine in a retrospective study, the prevalence of hBoV, compared with common respiratory viruses (RV), in respiratory specimens from patients with ARD. STUDY DESIGN: A total of 335 specimens obtained over 7 years were examined. Two hundred were nasal swabs from infants hospitalized for ARD, 84 were nasal swabs or bronchoalveolar lavages from adults with pneumonia, bronchopneumonia or asthma, and 51 were nasal swabs from healthy children. RESULTS: The overall rate of hBoV detection in specimens from infants with ARD, which was 4.5%, varied slightly from year to year, except for the period 2000-2002, when no specimen was positive. Unlike other RV, no seasonal variation in hBoV incidence was noted. Infants with hBoV infection suffered either from bronchiolitis or from bronchopneumonia and 5 out of 9 cases yielded no co-infecting viral pathogen. Only one sample from an adult was hBoV positive. None of the nasal swabs from healthy subjects tested hBoV-positive. CONCLUSIONS: The findings indicate that hBoV can cause ARD in infants. PMID- 17336144 TI - Prevalence of primary versus reactivated Epstein-Barr virus infection in patients with VCA IgG-, VCA IgM- and EBNA-1-antibodies and suspected infectious mononucleosis. AB - BACKGROUND: In Epstein-Barr virus (EBV) infection, IgG- and IgM-antibodies to viral capsid antigen (VCA) and IgG-antibodies to Epstein-Barr nuclear antigen 1 (EBNA-1) can occur simultaneously both in late primary infection and during subclinical viral reactivation in immunocompetent persons, and the differential diagnosis is of importance. OBJECTIVES: To study the prevalence of primary infection and serological reactivation in patients with suspected primary EBV infection and with all three parameters present. STUDY DESIGN: Fifty serum samples from 43 consecutive patients referred for suspected infectious mononucleosis and positive for VCA IgG-, VCA IgM- and EBNA-1-antibodies by EIA, were tested for IgG-antibody avidity with an EBV IgG immunoblot. Sera were also tested for heterophile antibodies (HA). To verify the presence of IgM-antibodies an EBV IgM immunoblot was performed when high-avidity IgG-antibodies were found. RESULTS AND CONCLUSIONS: Of 43 patients with suspected primary EBV infection and VCA IgG-, VCA IgM- and EBNA-1-antibodies present, only 18 patients (42%) had a late primary infection. Twenty-one patients (49%) had high-avidity IgG antibodies, indicating an IgM response due to reactivation, thus suggesting other causes for their symptoms. In 10 of these 21 patients the presence of IgM antibodies was confirmed by immunoblot, indicating reactivation as a cause of IgM antibodies in at least 23% of the 43 patients studied. Of 18 patients with primary infection, HA were detected in 16 (94%) of 17 patients tested. Only one (5%) of the patients with high-avidity antibodies had HA. Absence of HA in patients with this serological pattern is therefore a good indicator of reactivation, and conversely, the presence of HA is a good indicator of primary infection. In HA negative patients, avidity testing could be used for differential diagnosis. PMID- 17336145 TI - Semantic priming modulates the N400, N300, and N400RP. AB - OBJECTIVE: To determine whether ERP components can differentiate between the semantic priming mechanisms of automatic spreading activation, expectancy, and semantic matching. METHODS: The present study manipulated two factors known to differentiate semantic priming mechanisms: associations between words (forward, backward, and symmetrical) and prime-target stimulus onset asynchrony (SOA). Twenty-six participants were tested in each SOA condition while high-density 128 channel data were collected. Principal components analysis was applied to separate the ERP components. RESULTS: Priming was observed for all conditions. Three semantic components were present: (1) the standard N400 effect for symmetric and forward priming pairs at both short and long SOAs, (2) an N300 for the long SOA symmetric priming pairs, and (3) a right-lateralized posterior N400RP for long SOA backward priming pairs. CONCLUSIONS: Results suggest that the N300 reflects expectancy, but only for categorical and/or semantic similarity priming. Results further suggest that the N400RP is a replicable ERP component that responds to semantic matching. There is also some evidence that the N400 indirectly responds to both ASA and expectancy, perhaps as part of a post-lexical updating process and that backward priming at short SOAs is different from that at long SOAs. SIGNIFICANCE: Improved understanding of the semantic properties of the N400 and related ERP components may increase their utility for understanding language processes and for diagnostic purposes. PMID- 17336146 TI - Abnormal intracortical facilitation in early-stage Huntington's disease. AB - OBJECTIVE: It is known from neuropathological and imaging studies that the neuronal degeneration in Huntington's disease (HD) is already quite severe when the first symptoms of the disease become clinically evident. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the neurodegeneration in HD. METHODS: Motor cortex excitability was examined in 12 patients with HD in the early clinical stage of the disease and in 15 age-matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, the short-interval paired-pulse intracortical inhibition (SICI) and the paired-pulse intracortical facilitation (ICF) were examined. RESULTS: The early-stage HD patients showed a statistically significant reduction in ICF. The other measures did not differ significantly from the control subjects. CONCLUSIONS: Our findings provide neurophysiological evidence that changes in motor function are present in the early HD. Since ICF is thought to depend upon the activity of intracortical glutamatergic excitatory circuits, the results of our study support the theory that altered NMDA receptor function plays an important role in the pathogenesis of HD. SIGNIFICANCE: These findings may provide clues to the underlying pathophysiology of the disease. A more complete understanding of the changes in motor cortex excitability that occur early in the course of HD will lead to a better definition of the disease process and may allow earlier diagnosis and intervention. PMID- 17336147 TI - Neuropathies of the foot. AB - Compared with the common neuropathies affecting the hands (carpal tunnel syndrome and ulnar neuropathy), neuropathies of the feet have received less attention in the past. This is partly because of the rarity of these disorders as well as the lack of reliable electrophysiological tests for them. Over the years, nerve conduction tests for various nerves of the feet have been reported, and at this time techniques for all the nerves of the feet are available to the electromyographer. This review will provide up-to-date information on the current status of the research and issues relating to the neuropathies of the foot, with an emphasis on the most useful tests and the caveats for clinical neurophysiologists. PMID- 17336148 TI - Quantification of urinary chorionic gonadotropin in spontaneous abortion of pre clinically recognized pregnancy: method development and analytical validation. AB - Determination of environmental impacts on reproductive health and specifically on the incidence of early spontaneous abortion requires accurate estimates of the latter. This negative reproductive outcome can be detected by the pattern of elevation and decline of human chorionic gonadotropin (hCG) levels near and shortly beyond the expected time of implantation, requiring daily biomonitoring of hCG levels during the relevant period of the menstrual cycle. Prospective pregnancy studies to assess effects of potentially toxic exposures on human reproductive outcomes can involve up to three menstrual cycles and a huge number of samples in each, for the quantification of the inherently very low hCG levels usually can be determined only in serum. The invasive nature of blood collection, the number of samples needed for the development of prospective studies, and the lack of quantitative methods for the determination of low hCG levels in urine point to the need for collecting urine rather than blood and make it imperative to develop suitable quantitative methods for biomonitoring of very low levels of hCG in urine. This paper describes the development and validation procedures of an automated solid-phase two-site chemiluminescent immunometric assay for the quantification of urinary hCG in early pregnancy and early pregnancy loss. For the validation, both undiluted and diluted urine and control samples have been prepared. From the results, it can be concluded that the assay has a calibration range that extends to 5000 mIU/ml, with a detection limit of approximately 1.2 mIU/ml, practically identical to that found by the IMMULITE 2000 manufacturer's validation study. The intra- and inter-assay precision ranges up to a maximum of around 7%, meaning that the practical limit for functional sensitivity can be established as low as 10%. This means that the immunoassay from DPC can identify, with relatively high confidence, non-pregnant women and the typical "rise and fall" pattern of early pregnancy loss through analysis of urine samples. Results also lead to the conclusion that there is a very good agreement between expected and observed urinary hCG levels indicative of good immunoassay accuracy for the studied range of hCG concentrations. In terms of analyte stability, it can be concluded that urinary hCG is stable under the expected conditions required for ongoing investigations that include temperatures of 2-8 degrees C for up to 48 h and temperatures of around -20 degrees C for longer periods that can extend to over 3 months. PMID- 17336149 TI - Bavarian breast milk survey--pilot study and future developments. AB - For more than 20 years the Bavarian Health and Food Safety Authority has carried out breast milk analyses of persistent pesticides and selected organohalogen compounds. On the one hand, continuous monitoring of the levels of these chemicals in human breast milk shows a decreasing trend over these two decades. On the other hand, the number of samples sent to our institution for analysis has continuously decreased. Given the unreliable data on burden of environmental chemicals as well as the toxicologically outdated spectrum of analyzed substances, a new concept for the monitoring of breast milk has been developed and tested within a pilot study. We present here first results on PCDD, PCDF and dioxin-like PCB (dl-PCB) concentrations in breast milk of 43 women living in Bavaria, Germany. The average concentration of PCDD, PCDF and dl-PCB were 4.93, 4.98 and 9.92 pg WHO-TEQ/g fat, respectively. The new surveillance program (Bavarian Monitoring of Breast Milk, BAMBI) should track time trends of chemicals' concentrations in breast milk, while also monitoring new chemicals, such as PBDE or PFC, on which little or no German data exist. PMID- 17336151 TI - Human exposure to heavy metals in the vicinity of Portuguese solid waste incinerators--Part 3: biomonitoring of Pb in blood of children under the age of 6 years. AB - As a part of environmental health surveillance programs related to Portuguese solid waste incinerators (SWI), two biomonitoring projects have been established to investigate additional exposure to lead in children under the age of 6 years living in the vicinity of those facilities. The above-mentioned programs, being the only ones in the country that integrate systematic observations on human exposure to heavy metals, have to provide systematic data from Portuguese regions on the extent and pattern of human exposure to heavy metals, namely to lead. The present paper is the third of a series of papers prepared to accomplish that objective in regards to lead exposure as evaluated by measuring lead levels in children under the age of 6 years. Altogether, 250 children from Lisbon and 247 from Madeira Island have already been involved in the investigation. The present study evaluates spatial and temporal trends of lead exposure, based on comparisons of children's blood lead levels, either stratified by living area (exposed and control groups), or by time of exposure (T0, the baseline time, and T1, after approximately 2 years of regular operation of the facilities). The results obtained correspond to a relatively reduced number of individuals. Possibly for this reason, they are not fully conclusive in relation to whether living in the vicinity of SWI represents an additional risk of higher exposure to lead. Time trends of lead exposure as evaluated by blood lead levels in children also do not show any clear pattern. These conclusions and the fact that altogether around 3% of children from the whole group have blood lead levels >or=10 microg/dl warrant further investigation in order to clarify the contribution of incinerator emissions to the levels of lead in children and to identify alternative sources for preventive purposes, taking into consideration the relevance of even low lead exposure from a public health perspective, mainly in relation to children. PMID- 17336152 TI - Influence of environmental and ground conditions on injury risk in rugby league. AB - While the theoretical basis for a relationship between ground and environmental conditions and injury in rugby league is compelling, corroborative research is far from substantive. This study investigated the relationship between environmental and ground conditions and injury risk in 156 semi-professional rugby league players. Injuries were prospectively recorded from 157 training sessions and 137 competitive matches played over two consecutive competitive seasons. Daily weather variables (maximum and minimum temperature, relative humidity, and rainfall) were recorded, while ground conditions were subjectively rated as heavy, slippery, firm, or hard. Regression analysis was conducted to examine the independent effects of the environmental variables, ground condition, session type (training, match), and the interaction between ground condition and session type on injury. Higher temperatures, greater humidity, and greater levels of rainfall were all associated (p<.05) with softer ground conditions. A higher 365-day rainfall was associated with fewer injuries. Both the number of injuries and injury rate were higher in matches than in training sessions and when ground conditions were harder. For both number of injuries and injury rate, there was a statistically significant interaction between ground condition and session type, with harder ground conditions resulting in a higher injury rate in matches, but not training sessions. In conclusion, in rugby league, ground conditions do not influence training injuries, however, both harder ground conditions and less rainfall are associated with a greater number of match injuries. PMID- 17336153 TI - Hip joint range of motion restriction precedes athletic chronic groin injury. AB - Although a restricted hip range of motion has been previously associated with chronic groin injury the temporal course of this association remains unclear. Accordingly the purpose of this prospective cohort study was to report preliminary findings examining whether hip joint range of motion restriction is associated with subsequent onset of athletic chronic groin injury. End-range internal and external hip joint range of motion was determined in 29 elite Australian football players, without previous history of groin injury. The players were followed for two subsequent playing seasons for the development of chronic groin injury. Four athletes developed chronic groin injury defined as at least 6 weeks of groin pain and missing match playing time. In athletes that developed chronic groin injury a lower body weight (p=0.02) and reduced total hip joint range of motion (p=0.03) were found to be associated. This study suggests that hip stiffness is associated with later development of chronic groin injury and as such may be a risk factor for this condition. This work should be viewed as preliminary and caution is advised in applying the conclusion to clinical practice as the numbers in this study were small. PMID- 17336154 TI - Trends in physical activity behaviours and attitudes among South Australian youth between 1985 and 2004. AB - Rising youth obesity is a serious public health concern. There is a widespread view that declining physical activity is contributing to this trend. A total of 929 young South Australians (age=9-15 years) were surveyed in 1985 and 2004 on usual physical activity in several contexts, including attitudes to physical activity. Eight of 10 South Australian schools participating in the 1985 Schools Health and Fitness Survey were revisited in 2004. Comparisons were made on: organised sport, active transport, physical education (PE), playground activity, vigorous physical activity (VPA), total leisure-time physical activity (LTPA), and attitudes to PE and school sport. The questionnaire and method of administration were identical in both surveys. There were no differences between surveys in club and school sport participation, walking to school, and reported enjoyment of PE and school sport. In 2004 fewer children rode to school, but PE classes were more frequent. The percentage of children who 'sit and talk' during school breaks had increased, with a decreased percentage of older girls who 'run around' during school breaks. There was a significantly higher LTPA in MET.min in 2004 for boys, which was particularly evident at higher percentiles. There were no changes in mean or distribution of LTPA for the whole sample or girls. The percentage of respondents reporting >/=3 bouts of VPA in the previous week rose from 51% (1985) to 76% (2004). There is no consistent evidence of declining physical activity among South Australian youth. It is apparent that physical activity in some contexts has declined, while in other contexts levels are the same or higher than in 1985. This underscores the complex nature of physical activity and the influences on this behaviour. PMID- 17336155 TI - Endurance of the ankle joint plantar flexor muscles in athletes with medial tibial stress syndrome: a case-control study. AB - Medial tibial stress syndrome (MTSS) is a common overuse leg injury seen in athletes and can be recalcitrant to management. This cross-sectional study aimed to determine if there are differences in the isotonic endurance of the ankle joint plantar flexor muscles in athletes with MTSS compared to athletes without MTSS. The isotonic endurance of the ankle joint plantar flexors was measured in 30 participants diagnosed with MTSS, and 30 reference participants that were matched to MTSS participants on the basis of age (+/-5 years), gender, BMI (+/ 5%) and type of sporting activity. The number of heel-rise repetitions of the participants in each group was compared for differences. There were no significant differences between participants with and without MTSS for age (p=0.34), height (p=0.40) or BMI (p=0.27). The mean number of heel-rise repetitions performed by participants in the MTSS group was significantly less than the reference group (mean 23, S.D. 5.6, versus mean 33, S.D. 8.6; p<0.001). These results suggest that athletes with MTSS have endurance deficits of the ankle joint plantar flexor muscles. Rehabilitation of athletes with MTSS should comprise training designed to enhance endurance of the lower limb musculature, including the ankle joint plantar flexors. It is not known whether a lack of endurance of the ankle joint plantar flexor muscles is the cause or effect of MTSS. PMID- 17336156 TI - A hydatid cyst of the interventricular septum diagnosed incidentally by multislice computed tomography. AB - Cardiac involvement of the hydatid disease is uncommon. In this report a case of 54-year-old patient with a hydatid cyst in the interventricular septum was presented. The cyst was detected incidentally by cardiac multislice computed tomography and transthoracic echocardiographic appearances of the cyst raised the suspicion of cardiac echinococcosis. The patient was referred to surgery immediately for the removal of the cyst in order to prevent the potentially life threatening complications. The postoperative period was uneventful and she was discharged on albendazole therapy. PMID- 17336157 TI - Signalling to suit function: tailoring phosphoinositide 3-kinase during T-cell activation. AB - Members of the CD28 family of co-receptors are crucial determinants of the outcome of T-cell activation. These receptors interact with ligands in the B7 family and either costimulate or co-inhibit signals through antigen-specific receptors. The T-cell-costimulatory molecules CD28 and inducible costimulator recruit and activate class 1A phosphoinositide 3-kinase (PI3K). Interestingly, the co-inhibitory molecules cytotoxic T lymphocyte antigen-4 and B and T lymphocyte attenuator also interact with class 1A PI3K. However, all co inhibitory receptors share an ability to oppose activation of the key PI3K effector protein kinase B (also known as Akt). Recent evidence suggests that distinct mechanisms exist to limit Akt activation by different co-inhibitory receptors. This article examines how differential positive or negative regulation of the PI3K-Akt signalling pathway by CD28 family receptors enables functional differences between the receptors. PMID- 17336158 TI - The unconventional role of LT alpha beta in T cell differentiation. AB - Lymphotoxin (LT)alphabeta, a member of the tumor necrosis factor cytokine superfamily, and its receptor, the LTbeta receptor (LTbetaR), have a well defined role in secondary lymphoid organogenesis but an unexpected function in T cell differentiation. Although earlier studies indicated that conventional T cell subsets were normal in mice deficient in the LTbetaR pathway, accumulating evidence indicates that the LTalphabeta-LTbetaR pathway has a pivotal role in the ontogeny of unconventional T cells, including gammadelta T cells and invariant natural killer T cells. The LTbetaR pathway seems to operate at distinct levels during thymic development. Double positive thymocytes regulate the differentiation of early thymocyte progenitors and gammadelta T cells through a mechanism dependent on LTbetaR. In addition, LTbetaR signaling in thymic stroma was proposed to affect central tolerance to peripherally restricted antigens. These findings highlight the complex cellular crosstalk between lymphoid and stromal compartments during thymic differentiation. PMID- 17336159 TI - Complement and coagulation: strangers or partners in crime? AB - The convergence between complement and the clotting system extends far beyond the chemical nature of the complement and coagulation components, both of which form proteolytic cascades. Complement effectors directly enhance coagulation. These effects are supplemented by the interactions of complement with other inflammatory mediators that can increase the thrombogenicity of blood. In addition, complement inhibits anticoagulant factors. The crosstalk between complement and coagulation is also well illustrated by the ability of certain coagulation enzymes to activate complement components. Understanding the interplay between complement and coagulation has fundamental clinical implications in the context of diseases with an inflammatory pathogenesis, in which complement-coagulation interactions contribute to the development of life threatening complications. Here, we review the interactions of the complement system with hemostasis and their roles in various diseases. PMID- 17336160 TI - Schistosomiasis and pregnancy. AB - Currently, schistosomes infect approximately 40 million women of child-bearing age, yet little is known about schistosome-associated morbidity in pregnant women and their offspring. Animal models indicate a deleterious effect of schistosome infection on maternal, fetal and neonatal outcomes. Case reports have documented maternal infection in association with poor birth outcomes, and two observational studies indicate that maternal schistosome infection might be associated with decreased birth weight. Rigorously identifying and quantifying the impact of schistosome infection on pregnancy outcomes with well-designed observational and treatment studies are crucial for improving birth outcomes in schistosome-endemic areas. In addition, studies that address the safety of praziquantel during pregnancy could lead to further adoption of the recent informal recommendation by the World Health Organization to treat schistosome-infected pregnant and lactating women. PMID- 17336161 TI - Integrating transcriptome, proteome and glycome analyses of Schistosoma biology. AB - Publication of the transcriptomes of Schistosoma mansoni and Schistosoma japonicum, in conjunction with the sequencing and assembly of their genomes, has generated a comprehensive picture of Schistosoma transcriptional and genomic diversity. Subsequently, researchers who study conjugal and developmental biology, tegumental composition and larval or egg, secretory and excretory products have used these data, in combination with the latest '-omics' technologies, to extend large-scale screens of the schistosome transcriptome, proteome and glycome. In this article, we review these postgenomic investigations and contend that the generated datasets provide a plethora of novel drug, vaccine and immunomodulatory targets that might be useful for developing new antischistosome agents. PMID- 17336162 TI - Effects of estrogen receptor subtype-selective agonists on autoimmune disease in lupus-prone NZB/NZW F1 mouse model. AB - The specific roles of estrogen receptor (ER) subtypes alpha and beta in mediating estrogen's influences on lupus autoimmunity are unknown. Herein we found that ovariectomized NZB/NZW F1 mice treated with propyl pyrazole triol (ERalpha selective agonist) had significantly shorter survival, earlier development of albuminuria, higher serum concentrations of total IgG and prolactin, increased serum levels of anti-DNA IgG3, IgG2a and IgG2b and decreased anti-DNA IgG1 level compared to vehicle controls. In contrast, diarylpropionitrile (ERbeta-selective agonist) administration significantly decreased serum anti-DNA IgG2b level but did not significantly affect serum levels of other anti-DNA IgG subclasses, serum total IgG or prolactin concentration, mortality or the occurrence of albuminuria. These findings suggest that ERalpha activation plays the predominant and immunostimulatory role in estrogen-mediated modulation of lupus while ERbeta activation appears to have a slightly immunosuppressive effect on this disease. ERalpha activation coincidentally increased serum prolactin concentrations and may accelerate lupus disease activity also through this mechanism. PMID- 17336163 TI - Sub-lethal concentration of arsenic interferes with the proliferation of hepatocytes and induces in vivo apoptosis in Clarias batrachus L. AB - We studied the hepatocellular alterations induced by sub-lethal concentrations (0.50 muM) of arsenic in Indian catfish Clarias batrachus L. Sub-lethal arsenic exposure altered serum aspartate aminotransferase and alkaline phosphatase levels and brought about significant changes in different serum biochemical parameters. Arsenic exposure reduced total hepatocyte protein content and suppressed the proliferation of hepatocytes in a time-dependent manner. Routine histological studies on liver documented arsenic-induced changes characterized by dilated sinusoids, formation of intracellular edema, megalocytosis, vacuolation and appearance of hepatic cells with distorted nuclei. Transmission electron microscopy of hepatocytes further revealed hyperplasia and hypertrophy of mitochondria, development of dilated rough endoplasmic reticulum and changes in peroxisome size with duration of arsenic exposure. Degeneration of mitochondrial cristae and condensation of chromatin was also evident in arsenic-exposed hepatocytes. A significant number of hepatocytes isolated from arsenic-exposed fish stained with annexin V and demonstrated DNA ladder characteristic of apoptosis. Single-cell gel electrophoresis of exposed hepatocytes also revealed the development of comets usually seen in apoptotic cells. Using specific inhibitors it was determined that the arsenic-induced apoptosis of hepatocytes was caspase-mediated, involving the caspase 3 pathway. PMID- 17336164 TI - Protective effect of lupeol and its ester on cardiac abnormalities in experimental hypercholesterolemia. AB - Hyperlipidemia is a major risk factor for the premature development of coronary heart disease and it has been shown to increase the incidence of myocardial ischemia and cardiac events. Pentacyclic triterpenes possess antiatherosclerotic, antioxidant, anti-inflammatory and cytoprotective effects. To study the effect of plant derived triterpene, lupeol and its ester lupeol linoleate, on lipid status and biochemical changes on heart tissue, male albino Wistar rats were fed high cholesterol diet (normal rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. There was a significant (p<0.001) increase in the levels of total cholesterol, triglycerides and phospholipids along with augmented activities of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in the heart tissue. Triterpenes treatment reduced the above alterations produced in hypercholesterolemic rats. The transmembrane enzymes, namely Na(+), K(+)-ATPase, Ca(2+)-ATPase and Mg(2+) ATPase showed a decrease in their activities. Triterpenes treatment reversed these levels, prevented the hypertrophic cardiac histology and restored the normal ultrastructural architecture. In conclusion, lupeol and lupeol linoleate intervention minimized the lipid abnormalities and abnormal biochemical changes induced by HCD fed rats. This shows that triterpenes possess cardioprotective effects which will be beneficial in hypercholesterolemic condition. Out of these two triterpenes tested, lupeol linoleate appeared to be even more effective than lupeol. PMID- 17336166 TI - Morphology and ultrastructure of the sympathetic celiac ganglion neurons projecting to the cardia and pylorus of the rat stomach. AB - The stomach receives sympathetic projections from the celiac ganglion. To determine what kinds of neurons in the celiac ganglion project to the cardia or the pylorus of the stomach, we injected the retrograde tracer Fluoro-Gold into the cardia and the retrograde tracer cholera toxin subunit b into the pylorus of the same animal. A few neurons (about 10%) innervating the cardia sent collateral projections to the pylorus. Ultrastructural observations revealed that the celiac ganglion contained oval, medium-sized to large neurons. They had a dark cytoplasm containing numerous free ribosomes, rough endoplasmic reticulum, mitochondria, lysosomes, several Golgi apparatuses, and an oval nucleus. The axon terminals were small and usually contacted thin processes extending from the dendrites or the soma. About half of the terminals contained round vesicles, while the rest contained pleomorphic vesicles. Both types of terminals made asymmetric synaptic contacts. We then retrogradely labeled the neurons projecting to the cardia and the pylorus with wheat germ agglutinin conjugated horseradish peroxidase to examine their ultrastructural characteristics. The neurons projecting to the cardia (33.3x22.4 microm) were similar to the neurons projecting to the pylorus (33.4x24.7 microm) in their size and ultrastructural appearance. The neurons not projecting to the stomach (40.4x28.0 microm) were significantly larger than the neurons projecting to the cardia or the pylorus. Only a few axosomatic terminals were found on the neurons projecting to the cardia (1.6 per somatic profile), the pylorus (1.3) or the neurons not projecting to the stomach (0.9). These results provide morphological bases for the sympathetic motor neurons innervating the stomach. PMID- 17336167 TI - Evolutionary relationships based on genetic and phenetic characters between Triatoma maculata, Triatoma pseudomaculata and morphologically related species (Reduviidae: Triatominae). AB - The maculata group currently comprises two species of Triatominae, Triatoma maculata and Triatoma pseudomaculata, which share morphologic and chromatic characteristics. In order to clarify the systematic status of these two vectors of Trypanosoma cruzi and to infer their evolutionary relationships, we performed an enzymatic, morphometric and cytogenetic comparison of them, also taking into account two sister species not included in the group (T. arthurneivai and T. wygodzinskyi). According to our results, T. maculata and T. pseudomaculata belong to distinct evolutionary lineages. Similarly, T. arthurneivai topotypes from Minas Gerais form an independent isolated group by morphometrics. Our results also support the specific status of the Triatoma population from Sao Paulo State (formerly referred to T. arthurneivai), and suggest the possibility that it is T. wygodzinskyi. Finally, we suggest that only the arboricolous T. pseudomaculata from northeast Brazil and the rupicolous sister species originated from Sao Paulo State should be classified together in the same group. PMID- 17336165 TI - Monocrotaline pyrrole induces Smad nuclear accumulation and altered signaling expression in human pulmonary arterial endothelial cells. AB - The mechanistic relationship between the widely used monocrotaline model of primary pulmonary hypertension and altered TGFbeta family signaling due to genetic defects in the Bone Morphogenetic Protein type II receptor in affected humans has not been investigated. In this study we use fluorescent microscopy to demonstrate nuclear translocation of Smad 4 in human pulmonary arterial endothelial cell (HPAEC) cultures treated with monocrotaline pyrrole (MCTP), Bone Morphogenetic Protein (BMP) and TGFbeta. While MCTP induced transient nuclear accumulation of phosphorylated Smad 1 (P-Smad 1) and phosphorylated Smad 2 (P Smad 2), only expression of P-Smad 1 was significantly altered in western blots. P-Smad 1 expression significantly increased 30 min following treatment with MCTP correlating with P-Smad 1 and Smad 4 nuclear translocation. Although a modest, but significant decrease in P-Smad 1 expression occurred 1 h after treatment, expression was significantly increased at 72 h. Evaluation of components of the signal and response pathway at 72 h showed decreased expression of the BMP type II receptor (BMPrII), no change in TGFbeta Activin Receptor-like Kinase 1 (Alk 1), no change in Smad 4 but increase in the inhibitory Smad 6, decrease in the alternate BMP signaling pathway p38(MAPK) but no change in the psmad1 response element ID 1. Our results suggest transient activation of Smad signaling pathways in initial MCTP endothelial cell toxicity, and a persistent dysregulation of BMP signaling. Electron microscopy of cell membrane caveoli revealed a dramatic decrease in these structures after 72 h. Loss of these structural elements, noted for their sequestration and inhibition of receptor activity, may contribute to prolonged alterations in BMP signaling. PMID- 17336168 TI - Simultaneous determination of total homocysteine, cysteine, cysteinylglycine, and glutathione in human plasma by high-performance liquid chromatography: application to studies of oxidative stress. AB - A sensitive, reproducible, and robust high-performance liquid chromatography (HPLC) method has been validated for simultaneously determining total concentrations of the aminothiols homocysteine, cysteine, cysteinylglycine, and glutathione in human plasma. Plasma aminothiols are reduced via incubation with tris-(2-carboxyethyl)-phosphine hydrochloride, followed by protein precipitation with trichloroacetic acid and derivatization with ammonium-7-fluorobenzo-2-oxa 1,3-diazole-4-sulfonic acid. Separation of aminothiols and the internal standard mercaptopropionylglycine is achieved using reversed-phase HPLC conditions and fluorescence detection. Excellent linearity is observed for all analytes over their respective concentration ranges with correlation coefficients (r) > 0.99. The intra- and inter-day precision and accuracy were within +/-10%. This method utilizes an internal standard, employs phosphate buffered saline-based standards and quality controls, and demonstrates excellent plasma recovery and improved sensitivity. This assay is well suited for high-throughput quantitative determination of aminothiols in clinical studies, and is currently being used to support investigations of oxidative stress in patients with chronic kidney disease. PMID- 17336169 TI - Liquid chromatography-mass spectrometry assay for quantification of Gluten Exorphin B5 in cerebrospinal fluid. AB - A sensitive, precise and accurate method for the quantification of the alimentary opioid peptide Gluten Exorphin B5 (GE-B5, Tyr-Gly-Gly-Trp-Leu) in cerebrospinal fluid (CSF) was developed using liquid chromatography-mass spectrometry (LC-MS). Aliquots (10 microL) of sheep CSF were injected into a LC-MS instrument equipped with a reversed-phase C12 column at a flow rate of 250 microL/min. The mobile phase consisted of Eluent A water with 0.01% acetic acid as an ion-pairing reagent, and Eluent B acetonitrile. The LC-MS system was programmed to divert column flow to waste for 3.5 min after injection, after which time flow was directed into the mass spectrometer that operated in positive ion mode. DADLE (Tyr-D-Ala-Gly-Phe-D-Leu) was used as Internal Standard. No significant interfering peaks were detected at the retention times of GE-B5 in CSF blanks. The calibration curves were linear in the range of 0.39-78.00 ng/mL. The lower limit of detection and the lower limit of quantitation values for GE-B5 in CSF were established at 0.30 and 0.78 ng/mL, respectively. The intra-day and inter day precision values were <12% relative standard deviation. The intra-day and inter-day accuracy were 99.46-100.86% and 98.95-100.02%, respectively. Recovery of GE-B5 in CSF samples was greater than 80%. Stability studies indicate that GE B5 in CSF undergoes significant degradation (>55% after 600 min), which is reduced by the addition of protease inhibitors. This is the first reported method for the quantification of GE-B5 in CSF. PMID- 17336170 TI - Hepatitis B virus infection. AB - Hepatitis B virus (HBV) infection is a worldwide health problem and may cause acute, fulminant, chronic hepatitis, liver cirrhosis, or hepatocelullar carcinoma (HCC). Infection with HBV in infancy or early childhood may lead to a high rate of persistent infection (25-90%), while the rates are lower if infection occurs during adulthood (5-10%). In most endemic areas, infection occurs mainly during early childhood and mother-to-infant transmission accounts for approximately 50% of the chronic infection cases. Hepatitis B during pregnancy does not increase maternal mortality or morbidity or the risk of fetal complications. Approximately 90% of the infants of HBsAg carrier mothers with positive hepatitis B e-antigen (HBeAg) will become carriers if no immunoprophylaxis is given. Transplacental HBeAg may induce a specific non-responsiveness of helper T cells and HBcAg. Spontaneous HBeAg seroconversion to anti-HBe may develop with time but liver damage may occur during the process of the immune clearance of HBV and HBeAg. Mother-to-infant transmission of HBV from HBeAg negative but HBsAg positive mothers is the most important cause of acute or fulminant hepatitis B in infancy. Although antiviral agents are available to treat and avoid the complications of chronic hepatitis B, prevention of HBV infection is the best way for control. Screening for maternal HBsAg with/without HBeAg, followed by three to four doses of HBV vaccine in infancy and hepatitis B immunoglobulin (HBIG) within 24h of birth is the most effective way to prevent HBV infection. In areas with a low prevalence of HBV infection or with limited resources, omitting maternal screening but giving three doses of HBV vaccine universally in infancy can also produce good protective efficacy. The first universal HBV immunisation programme in the world was launched in Taiwan 22 years ago. HBV infection rates, chronicity rates, incidence of HCC and incidence of fulminant hepatitis in children have been effectively reduced. PMID- 17336171 TI - Congenital syphilis: a continuing but neglected problem. AB - Congenital syphilis was rare in most affluent countries but there has been a slight resurgence recently in several European countries. In large parts of the world and particularly sub-Saharan Africa congenital syphilis is a significant public health problem. The cornerstone of congenital syphilis control is antenatal screening and treatment of mothers with penicillin, which is a cost effective intervention. In affluent countries it should be strengthened among those at high risk. Clinicians should be more vigilant for the possibility of babies being born with congenital syphilis, which is often asymptomatic. In developing countries not only does antenatal care screening need to be strengthened by implementing point-of-care decentralised screening and treatment but alternative innovative approaches to controlling congenital syphilis should be explored. There is an urgent need for international health agencies to support focused approaches to tackling the tragedy of continuing congenital syphilis. This could be a part of a pro-poor strategy to meet the Millennium Development Goals. PMID- 17336172 TI - Growth factors and plasticity. AB - Neuroprotective strategies can prevent lesions from getting worse but agents that have neurotrophic properties can also affect repair in a developing brain. Although prevention and treatment in the early stages of brain lesions are desirable, delayed cell death or improved post-lesion plasticity are the only realistic targets in many cases. Several trophic factors can limit delayed cell death in animal models of perinatal brain damage. In addition, melatonin and brain-derived neurotrophic factor have been shown to promote post-lesion plasticity following neonatal excitotoxic white-matter damage in newborn mice. Despite these promising results, additional preclinical data are required for most of the trophic factors that have been tested, although some candidate drugs, e.g. melatonin or erythropoietin, might reach clinical trials in the near future. PMID- 17336173 TI - Management of women who use drugs during pregnancy. AB - Substance abuse in pregnancy is associated with significant maternal and fetal morbidity. The complication for care is that the mother is the cause of the problem that potentially harms not only herself but also her unborn child. The abuse is further complicated by the associated legal, social and environmental problems. The aim for the obstetrician is to provide a non-judgemental, supportive environment to minimise the risk, not only during pregnancy and the neonatal period, but also in the long term. To achieve this, caregivers need to be multidisciplinary and tolerant of the mother's problem. The aim of antenatal care is to reduce risk, which does not mean that the mother must abstain from drug use. The aim is to keep her within the care system and encourage her to take responsibility for her situation. No-one should be turned away or denied help as, ultimately, this is harmful to the mother and her baby. To provide this care, the obstetrician needs support from midwives, addiction counsellors, social workers, neonatologists, health visitors and general practitioners. Whereas the healthcare structure in the UK lends itself to this approach, this is not the case in other parts of the world. However, programmes of comprehensive antenatal care do not universally improve the health of the mother and the outcome of her pregnancy. The specifics of the care provided are probably less important than the quality of the care given and the degree of engagement of the individual. This chapter outlines the problems and potential solutions with reference to the service in Leeds in the UK. PMID- 17336174 TI - Placental calcium transporter (PMCA3) gene expression predicts intrauterine bone mineral accrual. AB - Evidence is accruing that environmental exposures during critical periods of early development induce persisting changes in skeletal growth, and alter fracture risk in later life. We have previously demonstrated that placental calcium transport, partly determined by maternal 25-(OH) vitamin D status, may underlie this phenomenon. However, the precise relationship between expression of calcium transport proteins in the human placenta, and neonatal bone mineral accrual in the offspring, remains unknown. Tissue samples from 70 human placentae were fast frozen in liquid nitrogen and stored at -70 degrees C. A quantitative real time reverse transcriptase polymerase chain reaction was used to measure the mRNA expression of PMCA isoforms 1-4, using beta-actin as a control gene. Neonatal whole body bone area, mineral content and areal density (BA, BMC, BMD) were measured within 2 weeks of birth using DXA. PMCA3 mRNA expression predicted BA (r=0.28, p=0.02), BMC (r=0.25, p=0.04), placental weight (r=0.26, p=0.04) and birth weight (r=0.33, p=0.006) of the neonate. In a multivariate model, the relationship between placental PMCA3 expression and neonatal BMC was independent of maternal height, pre-pregnant fat stores, parity, physical activity, smoking, and calcium intake (p<0.05). Expression of the placental calcium transporter PMCA3 mRNA predicts neonatal whole body bone mineral content. This association may explain, in part, the mechanism whereby a mother's 25(OH)-vitamin D stores influence her offspring's bone mass. PMID- 17336175 TI - Successful treatment of a bowel perforation after chemotherapy for Burkitt lymphoma. AB - Chemotherapy-induced intestinal perforation after treatment for Burkitt lymphoma is a known potential complication. However, there are very few reports in the pediatric literature that discuss this complication in any detail, and most incidents are secondary to surgical complications such as anastomotic leaks. Furthermore, there are no reports of children that have survived chemotherapy induced perforation, and thus, guidelines for the diagnosis and treatment of this complication or for the continuation of chemotherapy are lacking. We present a case of a 5-year-old boy who survived jejunal perforation after treatment for his Burkitt lymphoma, and the critical aspects of his care are discussed. PMID- 17336176 TI - Intestinal perforation caused by magnetic toys. AB - Accidental ingestion of foreign bodies is a common problem in children, but ingestion of magnets is rare. When multiple magnets are ingested, they may attract each other through the intestinal walls, causing pressure necrosis, perforation, fistula formation, or intestinal obstruction; as has been reported in 13 cases in the past 10 years. We report the fifth case in the literature of intestinal perforation and fistula caused by the ingestion of 2 small magnetic pieces of a toy by a 3-year-old boy. We find it necessary that sanitary authorities give more information to parents and physicians about the potential risks of these magnetic toys. PMID- 17336177 TI - Intercostal hernia and spontaneous pneumothorax in a liver transplant recipient: a case report. AB - Intercostal hernia can occur after blunt trauma and can also complicate thoracotomy. This report describes a 13-year-old liver transplant recipient with chronic asymptomatic intercostal hernia at site of thoracotomy. This hernia became manifest upon development of spontaneous pneumothorax. She presented with pleuritic pain and radiographic evidence of spontaneous pneumothorax. Her history included liver transplantation at age 19 months for tyrosinemia, posttransplant lymphoproliferative disorder at age 7 years with thoracotomy for lung biopsy, and prolonged corticosteroid administration. Examination and computed tomography revealed an intercostal hernia. She underwent repair of hernia, stapled resection of apical blebs, and pleurodesis. Reconstruction of chest wall involved rib fracture and intercostal approximation with nonabsorbable sutures covered by serratus muscle advancement. She is symptom free with intact repair 2 years and 9 months after surgery and is able to participate in vigorous physical activity. This is the first report of an intercostal hernia detected upon development of spontaneous pneumothorax. The hernia occurred at the site of a prior thoracotomy, possibly because of impaired healing from corticosteroid administration. This case suggests that nonabsorbable sutures should be used for intercostal approximation after thoracotomy in patients with impaired wound healing. PMID- 17336178 TI - Intrascrotal lipoblastoma: a case report and review of the literature. AB - Lipoblastomas are rare benign soft tissue tumors that occur primarily in young children. Most lipoblastomas occur in the extremities, trunk, head, and neck. An intrascrotal location is unusual. We describe the case of a 4-year-old boy with an intrascrotal lipoblastoma and discuss the differential diagnosis in reviewing the literature. PMID- 17336179 TI - Mathematical modeling in necrotizing enterocolitis--a new look at an ongoing problem. AB - Necrotizing enterocolitis (NEC) is the most common and lethal disease that affects the gastrointestinal (GI) tract of the premature infant. The etiology of NEC remains undefined. The only consistent epidemiological precursors for NEC are prematurity and enteral alimentation. Various inflammatory mediators, including tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, platelet-activating factor (PAF), and nitric oxide (NO) have been implicated in the pathogenesis of NEC, but the kinetics and role of these agents are ill defined. Currently, there are no biomarker predictors of NEC risk and severity. Sera or tissue from early time points in the development of the disease may help delineate early inflammatory events that predispose an individual to NEC, thus providing an interventional opportunity. We suggest that the lack of diagnostic and therapeutic modalities for NEC are due to the absence of a systems view of the disease, which in turn is hindered by a lack of sensitive physiological measurements that predict perturbations in the intestinal tissue compartment and an inability to reliably test serial samples for the presence of inflammatory mediators in small volumes and in a high-throughput manner. Computational modeling is a useful tool in the study of complex systems such as the inflammatory process. Computation models provide an "existence proof" for a given mechanism, uncover subtle inconsistencies between the underlying hypotheses and quantitative data, and force one to ask how much is known. We suggest that a properly validated and calibrated mathematical model of inflammation and its pathologic consequences in NEC will be useful for predicting the physiologic and biologic response in infants suffering from the disease. PMID- 17336180 TI - Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis. AB - BACKGROUND/PURPOSE: Failure of the gut barrier and endotoxemia have been implicated in sepsis and multiple organ failure (MOF) syndromes in adults. The contributions of endotoxin (ETX) and proinflammatory cytokines (CKs) to the pathophysiology of disease and the outcomes of infants in the neonatal intensive care unit (NICU) are not clear. We measured ETX and CK concentrations in infants who presented with clinical signs of sepsis and/or necrotizing enterocolitis (NEC) to study their impact on MOF and outcomes. METHODS: Blood samples from infants with signs of NEC and/or sepsis were collected for culture and determination of complete blood cell counts and concentrations of CKs (interleukin [IL]-1beta, tumor necrosis factor [TNF] alpha, and IL-6) and ETX at the onset of illness. Infants with signs of sepsis but without those of NEC were classified by blood culture results into a confirmed sepsis group (ie, positive culture) or a control group (ie, negative culture). Endotoxin concentrations were determined by chromogenic Limulus amebocyte lysate assay, and CK levels were quantitated by enzyme-linked immunoassay. Data are expressed as mean +/- SD and as odds ratios (ORs) with 95% confidence intervals (CIs). P values lower than .05 were considered to be significant. RESULTS: There was no demographic or clinical difference among the NEC (n = 27), sepsis (n = 44), and control (n = 56) groups, except that fewer (P = .02) infants in the NEC group (11%) had received maternal milk feedings as compared with infants in the sepsis group (23%) and those in the control group (39%). Endotoxin concentrations were higher (P < .0001) in the NEC group (3.30 +/- 2.11) as compared with the sepsis group (0.67 +/- .86) and the control group (0.09 +/- 0.24). Generalized linear regression analysis using formula feeding, mechanical ventilation, and gram-negative bacteremia as covariates demonstrated that NEC increased ETX concentrations independently (r = .80; P < .0001). Endotoxemia correlated with higher concentrations of all 3 CKs (P < .0001). There was an inverse association between ETX and both platelet count (r = -0.30; P = .0003) and absolute neutrophil count (r = -0.29; P = .0009). Infants who died of MOF had higher concentrations of ETX (2.83 +/- 3.04 vs 0.67 +/- 1.04 EU/mL; P < .0001), IL-1beta (509 +/- 493 vs 106 +/- 223 pg/mL; P < .0001), IL-6 (416 +/- 308 vs 99 +/- 165 pg/mL; P < .0001), and TNF-alpha (503 +/- 449 vs 126 +/- 237 pg/mL; P < .0001) as compared with those without MOF. Eighty six percent of the infants with MOF died. Multivariate logistic regression analysis demonstrated that higher ETX concentrations (OR = 2.47; 95% CI = 1.39 4.40; P = .002) and lower gestational age (OR = 1.41; 95% CI = 1.12-1.77; P = .003) predicted mortality. CONCLUSIONS: Neonatal endotoxemia and release of proinflammatory CKs are important contributors to MOF and mortality in the NICU. Endotoxemia was most severe at the onset of illness among the infants with NEC, suggesting that gut barrier failure plays an important role in adverse outcomes in the NICU. PMID- 17336181 TI - Intestinal mucosa remodeling by recombinant human epidermal growth factor(1-48) in neonates with severe necrotizing enterocolitis. AB - BACKGROUND AND AIMS: Neonatal necrotizing enterocolitis (NEC) is a common and serious acquired gastrointestinal tract condition. This clinical study assessed the potential clinical efficacy and microscopic effects of recombinant human epidermal growth factor 1-48 (EGF(1-48)) in neonates with NEC. METHODS: This prospective, double-blind, randomized controlled study included 8 neonates with NEC. The study compared the effects of a 6-day continuous intravenous infusion of EGF(1-48) at 100 ng kg(-1) h(-1) against placebo. Clinical outcomes and morphological evaluation of serial rectal mucosal biopsies were assessed at baseline and 4, 7, and 14 days after starting EGF infusions. RESULTS: There was no difference between the clinical safety outcomes recorded for EGF(1-48) or placebo patients. Quantitative morphologic differences in the rectal mucosa biopsies were noted with EGF(1-48) treatment compared with baseline or placebo and included a statistically significant increase in the number of mitoses per mucosal crypt on study day 4, significantly increased thickness of rectal mucosa from baseline on study days 4 and 7, and increased crypt surface area of rectal mucosa in parallel with increased mucosa thickness on day 14. CONCLUSION: This study of EGF(1-48) in neonates with severe NEC showed that growth factor treatment was well tolerated and produced positive and measurable remodeling trophic effects on the gastrointestinal mucosa. PMID- 17336182 TI - Triple tube therapy: a novel enteral feeding technique for short bowel syndrome in low-income countries. AB - BACKGROUND/PURPOSE: Short bowel syndrome (SBS) is a global malabsorption syndrome that results from extensive intestinal resection. We report our experience of 10 neonates with short bowel managed by a novel triple tube enteral feeding technique. The aim of this research was to provide justification for enteral nutritional strategies to enhance intestinal adaptation, especially in developing countries where parenteral nutrition is either unavailable or expensive. METHODS: From March 2004 to January 2006, 10 neonates underwent extensive bowel resection, enterostomy, and mucous fistula for necrotizing enterocolitis or midgut volvulus and were managed postoperatively with triple tube enteral feeding technique. Gestational age, birth weight, primary abdominal pathology, timing of surgery, surgical procedure performed, complications, duration and feasibility of refeeding, and weight gain were recorded. RESULTS: The group was composed of 8 male and 2 female neonates with a mean gestational age of 34.2 +/- 4.6 weeks and mean birth weight of 2580 +/- 993 g. Necrotizing enterocolitis accounted for 7 (70%) and midgut volvulus accounted for 3 (30%) cases of SBS. Mean gestational age at surgery was 35.5 +/- 2.2 weeks. Mean residual small bowel length and colon length after resection were 35.5 +/- 3.5 and 30.5 +/- 1.5 cm, respectively. Weight gain during refeeding ranged from 3 to 6 g/kg per day with duration of refeeding lasting 20 to 156 days. Reanastomoses was done 92 +/- 4.2 days after the primary surgery. There were 3 surgery-related complications, but no mortality. Mean period of follow-up was 12 +/- 2.4 months. Five of the 10 children are now 19 months old and have a body weight of -1.5 +/- 0.64 SD scores and height of -1.75 +/- 0.99 SD scores. CONCLUSION: This technique represents a safe and effective enteral nutrition strategy that eliminates the need for total parenteral nutrition for SBS in developing countries. PMID- 17336183 TI - Wilms' tumorigenesis is altered by misexpression of the transcriptional co activator, CITED1. AB - PURPOSE: Wilms' tumors arise from arrested differentiation of renal progenitor cells. CITED1 is a transcriptional regulator that blocks the metanephric mesenchymal-to-epithelial conversion and is expressed in the blastema of both the developing kidney and Wilms' tumors. We hypothesized that alterations of CITED1 dependent signaling promote persistence of blastema and thereby subject these pluripotent cells to future oncogenic events. METHODS: We used a retroviral delivery system to overexpress the full-length CITED1 (F/L) protein and 2 deletion mutants lacking either of its known functional domains, deltaSID (Smad-4 Interacting Domain) and deltaCR2 (Conserved Region 2; the CITED1 transactivation domain), in a human Wilms' tumor cell line that endogenously expresses CITED1. In vitro effects on cellular proliferation and apoptosis were assayed. In vivo effects on tumorigenesis, growth, proliferation, and apoptosis were determined after heterotransplantation into immunodeficient mice (n = 15 per cell line). RESULTS: In vitro, overexpression of CITED1-F/L significantly increased, whereas overexpression of the functionally inactivating mutant, CITED1-deltaCR2, significantly reduced cellular proliferation relative to the other lines (P < .0001). In vivo, Wilms' tumor incidence was significantly reduced in animals injected with cells overexpressing the mutant CITED1-deltaCR2 (7%) compared with CITED1-F/L (40%, P = .03) and CITED1-deltaSID (60%, P < .002). Similarly, mean tumor volume was least in the CITED1-deltaCR2 animals when compared with CITED1 F/L (P = .03) and CITED1-deltaSID animals (P < .005). Furthermore, the CITED1 deltaCR2 tumor showed the least cellular proliferation. Misexpression of CITED1 did not affect apoptosis either in vitro or in vivo. CONCLUSIONS: Overexpression of CITED1 in a human Wilms' tumor cell line significantly increases proliferation in vitro, whereas mutation of its functionally critical transactivation domain (deltaCR2) significantly reduces proliferation. This mutation further perturbs tumorigenesis and tumor growth after heterotransplantation into immunodeficient mice. We speculate that overexpression of CITED1 promotes expansion of a rapidly proliferating population of blastema and thereby induces an unstable environment highly susceptible to future oncogenic events. PMID- 17336184 TI - Epidermal growth factor can induce apoptosis in neuroblastoma. AB - BACKGROUND/PURPOSE: In previous studies, incubation of doxorubicin-resistant neuroblastoma SK-N-SH (Dox-R) cells with epidermal growth factor (EGF) decreased extracellular signal-regulated kinase activation. Because extracellular signal regulated kinase activation is associated with cell proliferation, we hypothesized that EGF could induce apoptosis and decrease the rate of cell growth in these cells. METHODS: The growth of wild-type (WT) SK-N-SH and Dox-R cells after incubation with EGF concentrations ranging from 1 to 100 ng/mL was determined by a colorimetric assay. Apoptosis was assessed by Hoechst staining and DNA laddering in WT, Dox-R, and cisplatin-resistant cells treated with EGF (100 ng/mL). Cleaved caspase-3 and EGF receptor (human epidermal growth factor receptor [HER1-HER4]) expression were verified by Western blot and reverse transcriptase-polymerase chain reaction. RESULTS: Epidermal growth factor decreased WT cell growth at concentrations between 50 and 100 ng/mL; Dox-R cell growth was attenuated at all EGF concentrations. Apoptosis was observed in WT and Dox-R cells incubated with EGF. Maximal cleaved caspase-3 expression occurred in WT cells treated with EGF 100 ng/mL and in Dox-R treated with EGF 5 to 10 ng/mL. Epidermal growth factor did not induce apoptosis in cisplatin-resistant cells. HER2 and HER3 transcription was maximal in WT and Dox-R cells, respectively. CONCLUSIONS: Wild-type and Dox-R cells exhibited decreased cell growth after EGF treatment because of apoptosis. This involved caspase-3 activation and could work through HER2 and HER3 receptors. PMID- 17336185 TI - Implications of MYCN amplification in patients with stage 4 neuroblastoma who undergo intensive chemotherapy. AB - BACKGROUND/PURPOSE: This study aims to clarify the implications of MYCN amplification in patients with high-risk neuroblastomas treated with 2 different regimens of induction chemotherapy established by the Japan Study Group for Advanced Neuroblastoma. METHODS: Between 1985 and 2003 in Japan, 392 patients with stage 4 neuroblastomas who were older than 12 months were treated with 2 regimens of induction chemotherapy (the combination of cyclophosphamide [CTX], cisplatin [CDDP], pirarubicin, and vincristine or etoposide). Regimen 91A3 or 98A3 (A3) (CTX 2400 mg/m2, CDDP 125 mg/m2) was a higher dose combination of CTX and CDDP than regimen 85A1 or 91A1 (A1) (CTX 1200 mg/m2, CDDP 90 mg/m2). The 392 cases were classified into 3 groups (A, 1 copy; B, 2-9 copies; C, more than 10 copies) based on the MYCN amplification status by a Southern blot analysis. RESULTS: The 5-year overall survival rate (5-YS) was 41.1% for all 392 cases. Regarding the MYCN amplification status, the 5-YS was 46.6% for A group (n = 227), 22.7% for B group (n = 26), and 36.0% for C group (n = 139). A fluorescence in situ hybridization analysis showed the presence of the cells with more than 10 copies in cases with 2 to 9 copies based on the Southern blot findings. Of the 227 patients in a group, the 5-YS was 46.7% for the 70 cases treated by A3 and 47.0% for 154 cases treated by A1 (nonsignificant). The 5-YS of the 210 patients with stem cell transplantation (SCT) (51.%) was significantly better than that of the 127 patients without SCT (41.1%) (P < .05). CONCLUSIONS: Regarding the MYCN amplification status, the tumor aggressiveness might thus be different between 2 and 9 copies and a single copy of MYCN. In neuroblastomas with 2 and 9 copies of MYCN based on a Southern blot analysis, the MYCN amplification status should be analyzed using the fluorescence in situ hybridization method. Induction chemotherapy followed by SCT according to the Japan Study Group for Advanced Neuroblastoma protocol improved the outcome of neuroblastomas with MYCN amplification; however, obtaining a further improvement in the long-term survival of stage 4 neuroblastomas may therefore require the development of an even more effective treatment modality. PMID- 17336186 TI - Natural history and long-term follow-up of antenatally detected liver cysts. AB - BACKGROUND/PURPOSE: Antenatally detected liver cysts are rare; their diagnostic accuracy is unknown, and their management is controversial. This study assessed the natural history of these lesions. METHODS: We conducted a retrospective review of infants with isolated intrahepatic cysts that were detected antenatally. Data are expressed as median (range). RESULTS: Fifteen infants presented during the period 1991-2004 with an antenatally detected liver cyst. Their gestational age at detection was 22 (18-34) weeks, and the maximum diameter of their cyst was 23 (10-120) mm. Serial scans, which were performed in 9 fetuses, showed cyst enlargement in 5 cases, diminution in 1 case, and no change in 3 cases. In utero percutaneous aspiration was required in 1 infant. Three infants underwent postnatal surgery. One fetus (postfetal intervention) had a subtotal excision of a large subcapsular cyst filling the abdominal cavity on day 2. Another infant required partial excision and marsupialization (complex cyst arising from segment IV) at 5 months, and a third infant underwent a cyst cholecystostomy at 4 months. Postnatal investigations (including hepatic scintigraphy) suggested that the remaining lesions were either simple parenchymal (n = 10) or isolated intrahepatic choledochal (ie, type V; n = 2) cysts. The median follow-up for these patients was 44 (27-167) months. Serial postnatal ultrasonography showed cyst diminution in 4 cases, an enlargement in 1 case, and no dimensional change in 7 cases. CONCLUSIONS: Most antenatally detected liver cysts appear to be simple and of parenchymal origin and do not require fetal intervention. Their postnatal history is variable, but regression without treatment is seen in most cases. PMID- 17336188 TI - The effect of hydrocephalus on lower esophageal sphincter smooth muscle reactivity: experimental study. AB - PURPOSE: The aim of this study was to assess the pharmacophysiological significance of the enteric nervous system for the mechanical responses of lower esophageal sphincter (LES) in infantile rats with kaolin-induced hydrocephalus. MATERIAL AND METHODS: Hydrocephalus was created in 7-day-old rats by injection of kaolin into the cisterna magna. After 10 days, rats were decapitated. Contractile (KCl, carbachol) and relaxant (isoprenaline, papaverine) responses were determined by using in vitro muscle technique in isolated LES smooth muscle strips. RESULTS: The receptor-mediated contractile and relaxant response to carbachol and isoprenaline in the LES smooth muscle was impaired in rats with hydrocephalus. There was no significant difference in the KCl and papaverine response in hydrocephalic and sham operated rats. CONCLUSION: Our findings suggest that hydrocephalus may impair receptor-mediated contractile and relaxant activity of LES smooth muscle leading to gastroesophageal reflux. PMID- 17336187 TI - Which is better for esophageal substitution in children, esophagocoloplasty or gastric transposition? A 27-year experience of a single center. AB - BACKGROUND/PURPOSE: Esophagocoloplasty and gastric transposition are 2 major methods of esophageal substitution in children. The purpose of this study is to review the authors' experience with these 2 techniques and compare the complications of these operations to determine whether 1 method emerges superior to the other. METHODS: A total of 149 children underwent surgery: 115 children underwent esophagocoloplasty, and 34 children underwent gastric transposition. Most patients (113-75.8%) had long-gap esophageal atresia. The operative technique of esophagocoloplasty consisted of the interposition of the transverse colon maintained by a double vascular pedicle based on the left colic vessels and the marginal paracolic arcade. Gastric transposition was performed according to classical technique. The transposition of colon and stomach was performed using blunt mediastinal dissection in all patients without thoracotomy. Complications and mortality of the 2 groups of patients were compared. These complications were classified as minor (cervical anastomosis leak, abdominal evisceration, diarrhea, strictures, and reflux to the interposed viscera) and major (necrosis of transposed viscera, dehiscence of an intra-abdominal or intrapleural suture, torsion of transposed viscera, delayed gastric emptying requiring reoperation, and cologastric anastomosis stricture). RESULTS: There were 2 graft necrosis, 1 (0.8%) in the esophagocoloplasty group and another (2.9%) in the gastric transposition group. Patients who underwent esophagocoloplasty experienced a greater incidence of minor complications (P = .001) and less major complications in comparison with the gastric transposition group (P = .001). All minor complications were treatable and had no consequences. No difference was noted between the 2 groups with regard to the mortality rate (0.9% and 5.9%, respectively, P > .05). CONCLUSIONS: Esophagocoloplasty and gastric transposition are satisfactory means of esophageal substitution in children. Considering the incidence of major postoperative complications, esophagocoloplasty must be the first choice for esophageal replacement in children. PMID- 17336189 TI - Congenital diaphragmatic hernia: a simplified postnatal predictor of outcome. AB - BACKGROUND/PURPOSE: The incidence of congenital diaphragmatic hernia (CDH) approximates 1 in 3000 births, with mortality rates up to 50%. The ability to accurately and easily predict the outcomes of these infants could be a valuable management tool. The purpose of this study was to develop and validate a simplified clinical method for predicting survival outcomes in infants born with CDH. METHODS: The Wilford Hall/Santa Rosa clinical prediction formula (WHSR(PF) = highest PaO2 - highest PCO2) was generated from arterial blood gas values obtained during the initial 24 hours of life, but before surgical repair or extracorporeal membrane oxygenation, in a local group of infants with CDH identified by prospective and retrospective review. The WHSR(PF) was validated using a comparative group from the Congenital Diaphragmatic Hernia Study Group (CHDSG). Bivariate, multivariable, and area under the receiver operating curve (AUC) analysis was performed using SigmaStat and SPSS statistical programs (SPSS, Chicago, Ill). RESULTS: As initially developed from the local data, the WHSR(PF) had a positive predictive value (PPV) of 82%, a negative predictive value of 88% and AUC of 0.87. When validated against the CDHSG data, the positive predictive value was 83%, negative predictive value was 66%, and AUC 0.79. Area under the receiver operating curve analysis by the previously published CDHSG predictive equation was 0.76. CONCLUSION: This novel formula is an easy to apply clinical tool with similar or better predictive abilities compared to previous methods of predicting survival in infants born with CDH. Currently, no method appears to have sufficient clinical accuracy for predicting the outcome of an individual infant with CDH. Further studies are indicated. PMID- 17336190 TI - Right congenital diaphragmatic hernia: an 18-year experience. AB - BACKGROUND: Prenatal diagnosis and outcome of right congenital diaphragmatic hernia (RCDH) are far less well known than the more common left CDH (LCDH). In addition, onset of RCDH beyond the neonatal period with a spectrum of atypical symptoms is not unusual. A retrospective analysis of RCDH treated at a single center over 18 years has been reviewed with regard to outcome after the introduction of a new treatment protocol for CDH. METHODS: All charts of patients with CDH between 1987 and 2004 were reviewed. Twenty-nine patients with RCDH were identified. The patients were divided into 2 historical groups: group 1, from 1987 to 1998 (16 patients), and group 2, from 1999 to 2004 (13 patients). From 1999, at the Department of Pediatric Surgery of Padua, the management of a baby born with CDH has been standardized and includes planned delivery at term, high frequency oscillatory ventilation since birth, inhaled nitric oxide if required, extracorporeal membrane oxygenation as a "last resort," and delayed repair once the infant is hemodynamically stable. Patients with either prenatal diagnosis of RCDH or early onset of symptoms (<6 hours of life) were considered "high risk," and those with late onset (>6 hours) were considered "low risk." RESULTS: Of 29 patients, prenatal diagnosis was available in 8 (27.5%) and major associated malformations in 8 patients (27.5%). Eight (50%) of 16 cases from group 1 and 9 (69.2%) of 13 cases from group 2 were high-risk patients. There was a trend in favor of a higher survival among high-risk patients from group 2 (25% vs 44%), although this was not statistically significant. As expected, all low-risk patients survived (P = .0001). Plain thorax x-ray was diagnostic in 23 (82.1%) cases, initially normal in 3, not performed in 1, and misinterpreted as right lower lobe pneumonia in 2. At operation, the prosthetic patch was required in 2 (9%) of 22 cases and the peritoneal sac was found in 4 (13.7%). CONCLUSIONS: (1) The rate of prenatal diagnosis of RCDH was low and remained stable throughout the examined period. (2) The introduction of a treatment protocol, using high frequency oscillatory ventilation since birth, improved the survival of high-risk patients with RCDH, although the data did not reach statistical significance. (3) The majority (75%) of low-risk patients presented beyond the first week of life with a variety of aspecific gastrointestinal or respiratory symptoms that accounted for initial misdiagnosis. (4) Even in these cases, the outcome was excellent. PMID- 17336191 TI - Early experience with the antegrade colonic enema stopper to reduce stomal stenosis. AB - BACKGROUND: Since the initial description of the antegrade colonic enema (ACE) procedure, stomal stenosis has been recognized as its most common complication. We previously reported that 44% of our patients required a dilatation for stomal stenosis, with 22% requiring surgical revision. We present our findings with the use of an ACE stopper (Medicina, Adlington, Lancashire, UK) as a means of avoiding this problem. METHODS: A retrospective review of the case notes of all patients who underwent an ACE procedure with a follow-up longer than 6 months was carried out over a 3-year period. Two weeks after the ACE procedure, an ACE stopper was sited in the conduit for at least 4 months and removed only for catheterization. RESULTS: Fourteen patients underwent an ACE procedure, 12 of whom received it laparoscopically. All patients received the ACE stopper. The patients' median age at surgery was 10 years (range, 5-16 years). Diagnoses included spinal dysraphism (n = 6) and anorectal malformation (n = 4), with soiling as the presenting complaint among all patients. The patients' median follow-up was 12 months (range, 6-39 months). There was no stomal complication, and 13 patients reported a marked improvement in soiling. CONCLUSIONS: The use of an ACE stopper has abolished stomal stenosis on short-term follow-up. We recommend the stopper as an adjunct to the overall management of concerned patients. Longer follow-up is required to establish the true effectiveness of this simple device. PMID- 17336192 TI - Umbilical pyloromyotomy: comparison of vertical linea alba and transverse muscle cutting incisions. AB - BACKGROUND: Pyloromyotomy is commonly performed through a supraumbilical skinfold incision. Entry into the peritoneal cavity can be achieved via a vertical linea alba incision or a transverse muscle cutting approach. The aim of this study was to compare the morbidity associated with these 2 operative techniques. METHODS: Case records of all babies undergoing umbilical pyloromyotomy between January 2000 and December 2004 were retrospectively compared for postoperative dehiscence, mucosal perforation, and wound infection (defined by the need for antibiotics or wound exploration). Data were analyzed with GraphPad Prism contingency tables and results were compared by Fisher exact test (P < .05). RESULTS: During the study period, 341 umbilical pyloromyotomies were performed at our institution. The surgeon was permitted choice of either operative approach (219 vertical linea alba, and 122 transverse muscle cutting). There were no significant differences between the 2 groups regarding age at presentation, sex, duration of symptoms, biochemical derangement, and operator seniority. No significant differences in morbidity were encountered with either of these 2 operative strategies. CONCLUSIONS: This study demonstrates that the vertical linea alba and transverse muscle cutting incisions have equivalent postoperative morbidity. These findings indicate that neither technique is demonstrably superior. PMID- 17336193 TI - Outcomes after a Ladd procedure for intestinal malrotation with heterotaxia. AB - PURPOSE: Intestinal rotation abnormalities and complex congenital heart disease associated with heterotaxia coexist. Despite the risk for midgut volvulus, performing a Ladd procedure for asymptomatic malrotation with heterotaxia remains to be controversial because the presumed risk for postoperative complications is thought to exceed the benefits of the operation. The purpose of this study was to review the incidence of complications after a Ladd procedure in asymptomatic patients with heterotaxia to guide recommendations for this patient population. METHODS: The medical records of all patients with heterotaxia who underwent a Ladd procedure for asymptomatic malrotation between 1984 and 2004 were reviewed. Type of cardiac disease, postoperative complications, and survival were recorded. RESULTS: Twenty-two patients (9 boys and 13 girls) with heterotaxia underwent an elective Ladd procedure after their medical stabilization or surgical correction or palliation of their cardiac anomaly. Of these patients, 19 were younger than 1 month at the time of the operation. The remaining 3 patients underwent the operation when they were between 2 and 5 months old. Three of the 22 patients (14%) developed postoperative intestinal obstruction: lysis of adhesions was performed in 1 patient; another patient required a staged bowel resection for a closed loop obstruction; and yet another patient had recurrent midgut volvulus 4 years after an incomplete initial Ladd procedure. All patients survived the initial and secondary procedures. Four deaths, all more than 1 month after the surgery, occurred as sequelae of the underlying cardiac anomaly. Length of follow up ranged from 1 to 17 years. CONCLUSIONS: We report on a 14% risk of postoperative bowel obstruction after an elective Ladd procedure, as compared with a small but significant incidence of midgut volvulus in patients with malrotation in the setting of complex congenital heart disease. Our results support the conclusion that an elective Ladd procedure at a time of relative cardiac stability for selected patients with heterotaxia has an acceptably low morbidity and should be considered to prevent midgut volvulus. PMID- 17336194 TI - Single-stage transanal endorectal pull-through for Hirschsprung's disease: perspective from a developing country. AB - BACKGROUND/PURPOSE: The aim of this study was to evaluate the feasibility, results, and cost-effectiveness of totally transanal endorectal pull-through (TEPT) in the management of rectosigmoid and midsigmoid Hirschsprung's disease (HD) in a low-income country. METHODS: Between March 2004 and December 2005, 19 children underwent totally TEPT procedure. The patients' ages ranged from 6 days to 13 years. The primary diagnosis in all 19 patients was HD confined to the rectosigmoid region in 15 and midsigmoid in 4. None had a preoperative colostomy. Follow-up period ranged from 4 to 20 months (mean, 8 months). RESULTS: Ages ranged from 0.25 to 65 months, with a mean of 16.24 months. Weights ranged from 3.4 to 13 kg, with a mean of 6.5 kg. Mean time from diagnosis to pull-through procedure was 26 days (range, 6-39 days). The mean length of rectosigmoid resection was 30 cm (range, 20-50 cm). The mean operative time was 95 minutes (range, 75-140 minutes). Mean intraoperative blood loss was 25 mL (range, 15-40 mL). There was one death unrelated to the procedure. One patient had enterocolitis 3 months postoperatively. Average frequency of defecation was 3 (range, 1-6) stools per day. TEPT was associated with a shorter operating time, less blood loss, early return to feeds, and an overall reduced cost. CONCLUSION: The safety and cost-effective benefits of transanal endorectal pull-through in the treatment of HD are of special interest for a developing country. Our data also suggest that functional outcome following TEPT is highly satisfactory and comparable with other established procedures. PMID- 17336195 TI - Repeated pull-through surgery for complicated Hirschsprung's disease--principles derived from clinical experience. AB - BACKGROUND: In some patients, an initial pull-through procedure for Hirschsprung's disease fails, and obstructive symptoms persist or recur. Then a repeated pull-through operation may be necessary. METHODS: Seventeen patients with Hirschsprung's disease aged 2 to 9 years (median, 4.6 years) have undergone a repeated pull-through procedure because of unresponsive symptoms after an initial operation. The initial procedure was Soave in 3 patients, Rehbein in 13 patients, and Duhamel in 1 patient. Surgical revision was indicated by incomplete resection of the transition zone in 16 patients, anastomotic strictures in 9 patients, and fistulas in 2 patients. All 17 patients have undergone Redo Duhamel pull-through procedure. Median follow-up after Redo operation was 9 years (range, 1-23 years). RESULTS: In 15 patients, the stooling pattern normalized immediately after Redo procedure. Two, including 1 with Down's syndrome, are prone to constipation with occasional use of laxatives. Soiling is seen in the patient with Down's syndrome, but only with episodes of diarrhea. In spite of large formation of scars surrounding the neoanorectum in most patients, Duhamel pull through reconstruction was possible in all children of this series. CONCLUSIONS: The predominant cause for persistent or recurrent unresponsive obstructive symptoms after initial pull-through procedure is incomplete resection of the transition zone. Less frequently, anastomotic strictures, rigidity of the anorectal cuff, and fistulas cause obstruction. Preoperative workup must focus on these complications. The courses after initial pull-through procedure show that laxatives, Malone procedure, dilatations of the anorectum, myectomy, V-Y-plasty, and injections of botulinum toxin cannot eliminate the mechanical or functional obstruction. Although a large formation of scars in the pelvis resulting from the initial operation, myectomies, dilatations, and other surgical modalities render a Redo revision more difficult, Redo Duhamel pull-through procedure is able to provide the definitive solution to the problem. PMID- 17336196 TI - Role of transanal endorectal pull-through in complicated Hirschsprung's disease: experience in 18 patients. AB - BACKGROUND/PURPOSE: In Hirschsprung's disease (HD) redo pull-through (PT) is indicated for anastomotic complications and for persistent aganglionosis after previous definitive surgery. This study was undertaken to evaluate the role of transanal approach to redo PT procedure in the management of complicated cases of HD over the last 7 years. PATIENTS AND METHODS: Between November 1998 and September 2005, 225 patients with HD were operated using the transanal endorectal PT (TEPT) approach. Eighteen patients had a redo PT owing to persistent aganglionosis. The present study evaluates the role of TEPT approach in patients with persistent aganglionosis (n = 18). Three patients needed a colostomy (n = 2) or ileostomy (n = 1) before the final operation. All the 18 patients underwent transanal mobilization (TEPT) of the colon. Six patients required additional mobilization of the proximal colon (n = 4) and the ileum (n = 2) during the redo PT operation. RESULTS: Median follow-up was 43 months (range, 3-72 months). Sixteen patients have had a good outcome with stool pattern 1 to 4 times daily. One patient had obstructive symptoms for 4 months postoperatively but then settled. One patient has occasional soiling. CONCLUSIONS: In this series, TEPT and posterior midline split of the muscle cuff were used with good results. This has the advantage of avoiding injury to the pelvic muscles and nerves. The TEPT approach is combined with transabdominal mobilization of the intestine depending on the length of the aganglionic segment. The outcome has been favorable, but long-term follow-up is necessary for full assessment of those patients. PMID- 17336197 TI - Adverse reactions to the Bacillus Calmette-Guerin vaccine in HIV-positive infants. AB - BACKGROUND: The Bacillus Calmette-Guerin (BCG) vaccine is routinely administered to newborn infants in South Africa. In 2000, a new vaccine, the Danish 1331 strain, was introduced into the Western Cape region. Red Cross Children's Hospital subsequently documented an increase in the number of complications arising from the new vaccine. Since 2004, HIV-positive infants have been treated with highly active antiretroviral therapy (HAART). Coinciding with the roll out of HAART there has been a significant and apparently paradoxical worsening of the complications of the BCG vaccine. METHODS: A retrospective analysis of all HIV positive infants referred to the surgical department for management of BCG vaccine complications. RESULTS: Fifteen infants were included in this study; they were all HIV-positive. Fourteen infants received HAART. In 10 patients, the implementation of HAART predated the complications of the BCG vaccine by an average of 1.4 months. CONCLUSION: We believe this to be the first description of BCG-associated immune reconstitution inflammatory syndrome. The implications for the operating surgeon are the unique management strategies that should be applied to this disease process and the ongoing research to determine which of these strategies is the most effective. PMID- 17336198 TI - Pelvic osteomyelitis: a diagnostic challenge in children. AB - BACKGROUND: Acute hematogenous osteomyelitis (AHOM) in children usually occurs in tubular bones. Acute hematogenous osteomyelitis of the pelvis is rare and is often not recognized primarily. METHODS: To review the experience with pelvic AHOM at our institution, we analyzed records from children diagnosed with pelvic AHOM (1984-2003) and compared with those reported in the literature. RESULTS: Among 220 children with AHOM (median age, 6.4 years), those 19 (9%) with pelvic AHOM were significantly older (median age, 9.0 years; range, 0.04-15.6). All children presented with limping or refused to walk. Twelve of 19 patients were febrile, 16 of 18 had elevated C-reactive protein (>20 mg/L), and 6 of 19 had leukocytes greater than 12 G/L. Staphylococcus aureus was isolated from blood or bone aspirates in 9 of 17 patients, and Streptococcus pneumoniae was isolated in 1. Scintigraphy was diagnostic in 15 of 15 children, and magnetic resonance imaging in 7 of 7 children. The mean time between initial symptoms and diagnosis was 3 days (range, 1-8 days). Infection resolved completely in all children after antibiotic therapy. CONCLUSION: Pelvic AHOM should be considered in children with limping and pain referred to the hip, thigh, or abdomen. Diagnosis by scintigraphy or magnetic resonance imaging followed by local puncture and microbiological workup allows for specific antibiotic treatment and results in an excellent outcome of pelvic AHOM. PMID- 17336199 TI - Recombinant granulocyte-macrophage colony-stimulating factor in the treatment of indolent ulcers with Klippel-Trenaunay-Weber syndrome: a case report. AB - Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital disease characterized by cutaneous hemangiomata, venous varicosities and osseous soft tissue hypertrophy of the affected limb. We report a case of a patient with KTWS who had developed severe chronic, non-healing cutaneous ulcers resulting from several angiography procedures with embolization by various agents. The ulcers were treated with perilesional granulocyte-macrophage colony-stimulating-factor (GM-CSF) with gratifying results. This case report suggests that GM-CSF may enhance the healing of chronic wounds not responding to other treatment modalities in patients with congenital angiodystrophy syndromes, thus salvaging a limb from amputation. PMID- 17336200 TI - Incomplete duplication of trachea with bronchogenic cyst: a case report. AB - Tracheal duplication is a very rare infant congenital airway anomaly. We report a bronchogenic cyst communicating with a tracheal duplication. This is the first reported case of pathologically confirmed duplication of trachea communicating with a bronchogenic cyst. PMID- 17336201 TI - Perivascular epithelioid cell tumour of the vagina in an 8 year old girl. AB - Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor with an unpredictable natural history. We present the first reported case of PEComa of the vagina diagnosed in an 8-year-old girl. This was initially diagnosed on biopsy as an embryonal rhabdomyosarcoma, and the patient underwent 3 cycles of chemotherapy according to the Mesenchymal Malignant Tumour 1989 protocol. A repeat scan, however, revealed an increase in tumor size. Total resection was achieved via a transvaginal (vertical sleeve) partial vaginectomy. The resected tumor had the typical appearance of a PEComa. Immunostains showed positive staining of tumor cells for HMB45, neuron-specific enolase, and calponin but were negative for S100 protein, melaninA, chromogranin, smooth muscle actin, desmin, caldesmon, epithelial membrane antigen, AE1/3, and synaptophysin. Six months after surgery, she remains free of tumor and is on follow-up with regular local examinations under anesthesia and computed tomography scans. Our case highlights the importance of an accurate initial diagnosis, and we stress the importance of regular surveillance over a significant period. PMID- 17336202 TI - Handlebar hernia: traumatic abdominal wall hernia with multiple enterotomies. A case report and review of the literature. AB - Handlebar hernia, caused by low-energy impact against a handlebar, is a localized abdominal wall hernia that is blunt enough not to penetrate the skin but severe enough to cause the disruption of abdominal wall musculature. In 1964, Roberts (Br J Surg 1964;51:153) reported the first case of a traumatic abdominal wall hernia that occurred in a 9-year-old boy after a fall upon a bicycle handle. Since then, 12 other cases have been reported. To the best of our knowledge, the case described here is the first documented case of an incarcerated handlebar hernia associated with a small bowel perforation and mesenteric disruption. PMID- 17336203 TI - Carbon dioxide embolism during laparoscopic cholecystectomy due to a patent paraumbilical vein. AB - Carbon dioxide embolism is a rare but potentially fatal complication of laparoscopic surgery. The most common cause is inadvertent injection of carbon dioxide into a large vein or solid organ during initial peritoneal insufflation. We describe a case of carbon dioxide embolism in a 13-year-old boy during an elective laparoscopic cholecystectomy, caused by injection of carbon dioxide into a large paraumbilical vein. The clinical manifestations of carbon dioxide embolism were hypotension, bradycardia, and an abrupt drop in end-tidal CO2. He subsequently did well and had no sequelae. Carbon dioxide embolism is a recognized complication of laparoscopic surgery, although the risk to the patient may be minimized by the surgical team's awareness of the problem, continuous intraoperative monitoring of end-tidal CO2, and using an open technique for initial access to the peritoneum. PMID- 17336204 TI - Ganglioneuroma of small bowel mesentery presenting as acute abdomen. AB - Ganglioneuroma is a rare benign tumor, usually seen in children and young adults, arising in the central nervous system. Ganglioneuroma of the mesentery is extremely rare; only one case has been recorded. We report the second case of a primary mesentery ganglioneuroma. The patient underwent surgical intervention for diagnostic and therapeutic purposes. PMID- 17336205 TI - A gasless abdomen does not exclude distal tracheoesophageal fistula: the value of a repeat x-ray. AB - A "gasless abdomen" in babies with esophageal atresia (EA) has traditionally been thought to imply absence of a distal tracheoesophageal fistula (TEF). We present 3 neonates with a provisional diagnosis of EA, who had a gasless abdomen on an initial x-ray taken within the first 4 hours of life. These children were subsequently shown to have gas in the stomach associated with a distal TEF. Two children were examined on subsequent repeat x-ray of the abdomen, when gas was demonstrated in the stomach. Another child had a laparotomy for a gastrostomy when a distended stomach was found. This baby went on to have a thoracotomy and a routine repair of the distal TEF and an esophageal anastamosis. Based on our data of 65 cases of EA and distal TEF, it is recommended that an x-ray of the abdomen is repeated before surgery is undertaken if the gasless abdomen is documented during the first 4 hours of life. PMID- 17336206 TI - Double reverse intestinal malrotation: a novel rotational anomaly and its surgical correction. AB - Reverse intestinal rotation is the rarest developmental anomaly of intestinal rotation and fixation. We present a case of an adolescent girl with chronic intermittent abdominal pain who was found to have a novel rotational abnormality that we have termed "double reverse intestinal malrotation." The imaging studies, operative findings, and the surgical correction are presented. PMID- 17336207 TI - Sternal cleft--a natural absurdity or a surgical opportunity. AB - Sternal cleft is a rare visually dramatic congenital anomaly. It results from failure of fusion of the 2 lateral mesodermal sternal bars by the 8 weeks of gestation. Superior clefts are more frequent than inferior ones, and isolated central clefts are extremely rare. We describe the case of a 4-year-old girl with a central sternal cleft that was closed autogenously with pectoralis major advancement flaps. PMID- 17336208 TI - The posterior urethra in anorectal malformations. AB - Anorectal malformations are commonly associated with recto-urethral fistulas. Definitive repair of these anomalies may result in injury to the bladder and urethra. Accurate preoperative assessment of the anatomy is imperative to identify the structures and avoid unnecessary injury. This brief report provides radiographic images that demonstrate these anomalies. PMID- 17336209 TI - Oxidative injury and hepatocyte apoptosis in total parenteral nutrition associated liver dysfunction. PMID- 17336211 TI - Scrotal abscess mimicking testicular torsion in infants and neonates. PMID- 17336213 TI - Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer. AB - PURPOSE: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). METHODS AND MATERIALS: Treatment began with two cycles of topotecan (1 mg/m(2)) Days 1 to 5 and paclitaxel (175 mg/m(2)) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard "cohorts of 3" design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m(2)) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade > or =4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade > or =3 dyspnea, or Grade > or =2 pneumonitis. RESULTS: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade > or =3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months. CONCLUSION: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine. PMID- 17336214 TI - Long-term outcomes in breast cancer patients with ten or more positive axillary nodes treated with combined-modality therapy: the importance of radiation field selection. AB - PURPOSE: To determine the long-term outcome of a consistent treatment approach with electron beam postmastectomy radiation therapy (PMRT) in breast cancer patients with > or =10 positive nodes treated with combined-modality therapy. METHODS AND MATERIALS: TSixty-three breast cancer patients with > or =10 positive lymph nodes were treated with combined-modality therapy using an electron beam en face technique for PMRT at the University of Florida. Patterns of recurrence were studied for correlation with radiation fields. Potential clinical and treatment variables were tested for possible association with local-regional control (LRC), disease-free survival (DFS), and overall survival (OS). RESULTS: TAt 5, 10, and 15 years, OS rates were 57%, 36%, and 27%, respectively; DFS rates were 46%, 37%, and 34%; and LRC rates were 87%, 87%, and 87%. No clinical or treatment variables were associated with OS or DFS. The use of supplemental axillary radiation (SART) (p = 0.012) and pathologic N stage (p = 0.053) were associated with improved LRC. Patients who received SART had a higher rate of LRC than those who did not. Moderate to severe arm edema developed in 17% of patients receiving SART compared with 7% in patients not treated with SART (p = 0.28). CONCLUSIONS: TA substantial percentage of patients with > or =10 positive lymph nodes survive breast cancer. The 10-year overall survival in these patients was 36%. The addition of SART was associated with better LRC. PMID- 17336215 TI - Adjuvant stereotactic permanent seed breast implant: a boost series in view of partial breast irradiation. AB - PURPOSE: The aim of this study was to use permanent seed implants in the breast and describe our experience with 15 cases, using iodine seed implants as a tumor bed boost. METHODS AND MATERIALS: Breasts were fixed with a thermoplastic sheet, a template bridge applied, the thorax scanned and the images rotated to be perpendicular to the implant axis. Skin, heart, and lung were delineated. A preplan was made, prescribing 50 Gy to the clinical target volume (CTV), consisting in this boost series of nearly a quadrant. Iodine (125) seeds were stereotactically implanted through the template, and results were checked with a postplan computed tomographic (CT) scan. RESULTS: The breast was immobilized reproducibly. Simulation, scanning, and implant were performed without difficulties. Preplan CTV D90% (the dose delivered to 90% of the CTV) was 66 Gy, and postoperative fluoroscopic or CT scan checks were satisfactory. Pre- and postplan dose-volume histogram showed good organ sparing: mean postplan skin, heart, and lung V30 Gy (the organ volume receiving a dose of 30 Gy) of 2 +/- 2.2 mL, 0.24 +/- 0.34 mL, and 3.5 +/- 5 mL, respectively. No short-term toxicity above Grade 1 was noted, except for transient Grade 3 neuropathy in 1 patient. CONCLUSIONS: Seeds remained in the right place, as assessed by fluoroscopy, absence of significant pre- to postplan dose-volume histogram change for critical organs, and total irradiated breast volume. The method could be proposed as a boost when high dosimetric selectivity is required (young patients after cardiotoxic chemotherapy for left-sided cancer). This boost series was a preliminary step before testing partial breast irradiation by permanent seed implant in a prospective trial. PMID- 17336216 TI - Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results. AB - PURPOSE: To evaluate the feasibility and toxicity of stereotactic hypofractionated accurate radiotherapy (SHARP) for localized prostate cancer. METHODS AND MATERIALS: A Phase I/II trial of SHARP performed for localized prostate cancer using 33.5 Gy in 5 fractions, calculated to be biologically equivalent to 78 Gy in 2 Gy fractions (alpha/beta ratio of 1.5 Gy). Noncoplanar conformal fields and daily stereotactic localization of implanted fiducials were used for treatment. Genitourinary (GU) and gastrointestinal (GI) toxicity were evaluated by American Urologic Association (AUA) score and Common Toxicity Criteria (CTC). Prostate-specific antigen (PSA) values and self-reported sexual function were recorded at specified follow-up intervals. RESULTS: The study includes 40 patients. The median follow-up is 41 months (range, 21-60 months). Acute toxicity Grade 1-2 was 48.5% (GU) and 39% (GI); 1 acute Grade 3 GU toxicity. Late Grade 1-2 toxicity was 45% (GU) and 37% (GI). No late Grade 3 or higher toxicity was reported. Twenty-six patients reported potency before therapy; 6 (23%) have developed impotence. Median time to PSA nadir was 18 months with the majority of nadirs less than 1.0 ng/mL. The actuarial 48-month biochemical freedom from relapse is 70% for the American Society for Therapeutic Radiology and Oncology definition and 90% by the alternative nadir + 2 ng/mL failure definition. CONCLUSIONS: SHARP for localized prostate cancer is feasible with minimal acute or late toxicity. Dose escalation should be possible. PMID- 17336217 TI - Germline glutathione S-transferase variants in breast cancer: relation to diagnosis and cutaneous long-term adverse effects after two fractionation patterns of radiotherapy. AB - PURPOSE: To explore whether certain glutathione S-transferase (GST) polymorphisms are associated with an increased risk of breast cancer or the level of radiation induced adverse effects after two fractionation patterns of adjuvant radiotherapy. METHODS AND MATERIALS: The prevalence of germline polymorphic variants in GSTM1, GSTP1, and GSTT1 was determined in 272 breast cancer patients and compared with that in a control group of 270 women from the general population with no known history of breast cancer. The genetic variants were determined using multiplex polymerase chain reaction followed by restriction enzyme fragment analysis. In 253 of the patients surveyed for radiotherapy induced side effects after a median observation time of 13.7 years (range, 7-22.8 years), the genotypes were related to the long-term effects observed after two fractionation patterns (treatment A, 4.3 Gy in 10 fractions for 156 patients; and treatment B, 2.5 Gy in 20 fractions for 97; both administered within a 5-week period). RESULTS: None of the GST polymorphisms conferred an increased risk of breast cancer, either alone or in combination. Compared with treatment B, treatment A was followed by an increased level of moderate to severe radiation induced side effects for all the endpoints studied (i.e., degree of telangiectasia, subcutaneous fibrosis and atrophy, lung fibrosis, costal fractures, and pleural thickening; p <0.001 for all endpoints). A significant association was found between the level of pleural thickening and the GSTP1 Ile105Val variant. CONCLUSION: The results of this study have illustrated the impact of hypofractionation on the level of adverse effects and indicated that the specific alleles of GSTP1, M1, and T1 studied here may be significant in determining the level of adverse effects after radiotherapy. PMID- 17336218 TI - Effect of epidermal growth factor against radiotherapy-induced oral mucositis in rats. AB - PURPOSE: We tested the efficacy of oral recombinant human epidermal growth factor (rhEGF) against radiation-induced oral mucositis in a rat model. METHODS AND MATERIALS: Each of 35 Sprague-Dawley rats, 7 to 8 weeks of age and weighing 178 +/- 5 grams, was irradiated once in the head region with 25 Gy, using a 4-MV therapeutic linear accelerator at a rate of 2 Gy/min. The irradiated rats were randomly divided into four groups: those receiving no treatment (Group 1), those treated with vehicle only three times per day (Group 2), and those treated with 50 microg/mL (Group 3), or 100 microg/mL (Group 4) rhEGF three times per day. RESULTS: Rats were monitored for survival rate and daily activity, including hair loss, sensitivity, and anorexia. We found that survival rate and oral intake were significantly increased and histologic changes were significantly decreased in the rhEGF-treated rats. There was no difference, however, between rats treated with 50 microg/mL or 100 microg/mL rhEGF. CONCLUSION: These findings suggest that orally administered rhEGF decreased radiation-induced oral mucositis in rats. PMID- 17336219 TI - Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor. AB - PURPOSE: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. METHODS AND MATERIALS: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by (19)F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. RESULTS: Large tumors (>3.0 cm(3)) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO(2)) than their smaller counterparts (<1.5 cm(3)). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO(2), and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO(2) > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. CONCLUSIONS: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy. PMID- 17336220 TI - Estrogens decrease gamma-ray-induced senescence and maintain cell cycle progression in breast cancer cells independently of p53. AB - PURPOSE: Sequential administration of radiotherapy and endocrine therapy is considered to be a standard adjuvant treatment of breast cancer. Recent clinical reports suggest that radiotherapy could be more efficient in association with endocrine therapy. The aim of this study was to evaluate the estrogen effects on irradiated breast cancer cells (IR-cells). METHODS AND MATERIALS: Using functional genomic analysis, we examined the effects of 17-beta-estradiol (E(2), a natural estrogen) on MCF-7 breast cancer cells. RESULTS: Our results showed that E(2) sustained the growth of IR-cells. Specifically, estrogens prevented cell cycle blockade induced by gamma-rays, and no modification of apoptotic rate was detected. In IR-cells we observed the induction of genes involved in premature senescence and cell cycle progression and investigated the effects of E(2) on the p53/p21(waf1/cip1)/Rb pathways. We found that E(2) did not affect p53 activation but it decreased cyclin E binding to p21(waf1/cip1) and sustained downstream Rb hyperphosphorylation by functional inactivation of p21(waf1/cip1). We suggest that Rb inactivation could decrease senescence and allow cell cycle progression in IR-cells. CONCLUSION: These results may help to elucidate the molecular mechanism underlying the maintenance of breast cancer cell growth by E(2) after irradiation-induced damage. They also offer clinicians a rational basis for the sequential administration of ionizing radiation and endocrine therapies. PMID- 17336221 TI - Dose calculation using megavoltage cone-beam CT. AB - PURPOSE: To demonstrate the feasibility of performing dose calculation on megavoltage cone-beam CT (MVCBCT) of head-and-neck patients in order to track the dosimetric errors produced by anatomic changes. METHODS AND MATERIALS: A simple geometric model was developed using a head-size water cylinder to correct an observed cupping artifact occurring with MVCBCT. The uniformity-corrected MVCBCT was calibrated for physical density. Beam arrangements and weights from the initial treatment plans defined using the conventional CT were applied to the MVCBCT image, and the dose distribution was recalculated. The dosimetric inaccuracies caused by the cupping artifact were evaluated on the water phantom images. An ideal test patient with no observable anatomic changes and a patient imaged with both CT and MVCBCT before and after considerable weight loss were used to clinically validate MVCBCT for dose calculation and to determine the dosimetric impact of large anatomic changes. RESULTS: The nonuniformity of a head size water phantom ( approximately 30%) causes a dosimetric error of less than 5%. The uniformity correction method developed greatly reduces the cupping artifact, resulting in dosimetric inaccuracies of less than 1%. For the clinical cases, the agreement between the dose distributions calculated using MVCBCT and CT was better than 3% and 3 mm where all tissue was encompassed within the MVCBCT. Dose-volume histograms from the dose calculations on CT and MVCBCT were in excellent agreement. CONCLUSION: MVCBCT can be used to estimate the dosimetric impact of changing anatomy on several structures in the head-and-neck region. PMID- 17336222 TI - Positioning accuracy of cone-beam computed tomography in combination with a HexaPOD robot treatment table. AB - PURPOSE: To scrutinize the positioning accuracy and reproducibility of a commercial hexapod robot treatment table (HRTT) in combination with a commercial cone-beam computed tomography system for image-guided radiotherapy (IGRT). METHODS AND MATERIALS: The mechanical stability of the X-ray volume imaging (XVI) system was tested in terms of reproducibility and with a focus on the moveable parts, i.e., the influence of kV panel and the source arm on the reproducibility and accuracy of both bone and gray value registration using a head-and-neck phantom. In consecutive measurements the accuracy of the HRTT for translational, rotational, and a combination of translational and rotational corrections was investigated. The operational range of the HRTT was also determined and analyzed. RESULTS: The system performance of the XVI system alone was very stable with mean translational and rotational errors of below 0.2 mm and below 0.2 degrees , respectively. The mean positioning accuracy of the HRTT in combination with the XVI system summarized over all measurements was below 0.3 mm and below 0.3 degrees for translational and rotational corrections, respectively. The gray value match was more accurate than the bone match. CONCLUSION: The XVI image acquisition and registration procedure were highly reproducible. Both translational and rotational positioning errors can be corrected very precisely with the HRTT. The HRTT is therefore well suited to complement cone-beam computed tomography to take full advantage of position correction in six degrees of freedom for IGRT. The combination of XVI and the HRTT has the potential to improve the accuracy of high-precision treatments. PMID- 17336223 TI - Online planning and delivery technique for radiotherapy of spinal metastases using cone-beam CT: image quality and system performance. AB - PURPOSE: To assess the feasibility of an online strategy for palliative radiotherapy (RT) of spinal bone metastasis, which integrates imaging, planning, and treatment delivery in a single step at the treatment unit. The technical challenges of this approach include cone-beam CT (CBCT) image quality for target definition, online planning, and efficient process integration. METHODS AND MATERIALS: An integrated imaging, planning, and delivery system was constructed and tested with phantoms. The magnitude of CBCT image artifacts following the use of an antiscatter grid and a nonlinear scatter correction was quantified using phantom data and images of patients receiving conventional palliative RT of the spine. The efficacy of online planning was then assessed using corrected CBCT images. Testing of the complete process was performed on phantoms with assessment of timing and dosimetric accuracy. RESULTS: The use of image corrections reduced the cupping artifact from 30% to 4.5% on CBCT images of a body phantom and improved the accuracy of CBCT numbers (water: +/- 20 Hounsfield unit [HU], and lung and bone: to within +/- 130 HU). Bony anatomy was clearly visible and was deemed sufficient for target definition. The mean total time (n = 5) for application of the online approach was 23.1 min. Image-guided dose placement was assessed using radiochromic film measurements with good agreement (within 5% of dose difference and 2 mm of distance to agreement). CONCLUSIONS: The technical feasibility of CBCT-guided online planning and delivery for palliative single treatment has been demonstrated. The process was performed in one session equivalent to an initial treatment slot (<30 min) with dosimetric accuracy satisfying accepted RT standards. PMID- 17336224 TI - Prostate volume contouring: a 3D analysis of segmentation using 3DTRUS, CT, and MR. AB - PURPOSE: This study evaluated the reproducibility and modality differences of prostate contouring after brachytherapy implant using three-dimensional (3D) transrectal ultrasound (3DTRUS), T2-weighted magnetic resonance (MR), and computed tomography (CT) imaging. METHODS AND MATERIALS: Seven blinded observers contoured 10 patients' prostates, 30 day postimplant, on 3DTRUS, MR, and CT images to assess interobserver variability. Randomized images were contoured twice by each observer. We analyzed length and volume measurements and performed a 3D analysis of intra- and intermodality variation. RESULTS: Average volume ratios were 1.16 for CT/MR, 0.90 for 3DTRUS/MR, and 1.30 for CT/3DTRUS. Overall contouring variability was largest for CT and similar for MR and 3DTRUS. The greatest variability of CT contours occurred at the posterior and anterior portions of the midgland. On MR, overall variability was smaller, with a maximum in the anterior region. On 3DTRUS, high variability occurred in anterior regions of the apex and base, whereas the prostate-rectum interface had the smallest variability. The shape of the prostate on MR was rounder, with the base and apex of similar size, whereas CT contours had broad, flat bases narrowing toward the apex. The average percent of surface area that was significantly different (95% confidence interval) for CT/MR was 4.1%; 3DTRUS/MR, 10.7%; and CT/3DTRUS, 6.3%. The larger variability of CT measurements made significant differences more difficult to detect. CONCLUSIONS: The contouring of prostates on CT, MR, and 3DTRUS results in systematic differences in the locations of and variability in prostate boundary definition between modalities. MR and 3DTRUS display the smallest variability and the closest correspondence. PMID- 17336225 TI - Image-guided total marrow and total lymphatic irradiation using helical tomotherapy. AB - PURPOSE: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. METHODS AND MATERIALS: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribs and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. RESULTS: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. CONCLUSION: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk. PMID- 17336226 TI - Effects of prescription depth, cylinder size, treatment length, tip space, and curved end on doses in high-dose-rate vaginal brachytherapy. AB - PURPOSE: To determine the effects of the prescription depth, cylinder size, treatment length, tip space, and curved end on high-dose-rate vaginal brachytherapy (HDR-VBT) of endometrial cancer. METHODS AND MATERIALS: Treatment plans were prescribed and optimized based on points at the cylinder surface or at 0.5-cm depth. Cylinder sizes ranging from 2 to 4 cm in diameter, and treatment lengths ranging from 3 to 8 cm were used. Dose points in various depths were precisely defined along the cylinder dome. The given dose and dose uniformity to a depth of interest were measured by the mean dose (MD) and standard deviation (SD), respectively, among the dose points belonging to the depth. Dose fall-off beyond the 0.5 cm treatment depth was determined by the ratio of MD at 0.75-cm depth to MD at 0.5-cm depth. RESULTS: Dose distribution varies significantly with different prescriptions. The surface prescription provides more uniform doses at all depths in the target volume, whereas the 0.5-cm depth prescription creates larger dose variations at the cylinder surface. Dosimetric uncertainty increases significantly (>30%) with shorter tip space. Extreme hot (>150%) and cold spots (<60%) occur if no optimization points were placed at the curved end. CONCLUSIONS: Instead of prescribing to a depth of 0.5 cm, increasing the dose per fraction and prescribing to the surface with the exact surface points around the cylinder dome appears to be the optimal approach. PMID- 17336228 TI - Salvage radiotherapy in patients with PET-Positive residual non-Hodgkin's lymphoma after chemotherapy: in regard to Kahn et al. (Int J Radiat Oncol Biol Phys 2006;66:961-965). PMID- 17336229 TI - The effect of metoclopramide on gastric emptying in traumatic brain injury. AB - OBJECTIVE: Gastric paresis in traumatic brain injury (TBI) hinders the effectiveness of enteral support in this patient group. In this study we have investigated the effect of metoclopramide on gastric emptying in TBI patients. METHOD: In this prospective, randomized, controlled, double-blind study, 19 TBI patients with Glasgow Coma Scale scores of 3-11 were included. In all patients, enteral nutrition was commenced with a nasogastric feeding tube within 48 hours of trauma. Patients were randomized into two groups. In the metoclopramide (M) group, 10 mg metoclopramide was delivered intravenously three times daily for 5 days. In the control (C) group, an equal volume of saline was administered. Besides demographics, gastric emptying according to a paracetamol absorption test at days 0 and 5, time to reach target nutritional requirements, gastric residues, intolerance to feeding, nutritional complications, and clinical outcomes were recorded for each patient. RESULTS: The gastric residue rates were 2.7+/-7.4 mL and 8.1+/-17.7 mL per 100 patient days for groups C and M respectively (p=0.408). Similarly, feeding intolerance and complication rates did not significantly differ between groups C and M, (respectively p=0.543 and 0.930). Gastric emptying parameters also were similar between the study groups. CONCLUSION: We were unable to document any advantage to using metoclopramide in TBI patients. Simple intragastric enteral feeding with close monitoring of the possible complications seems to be sufficient with acceptable morbidity rates. PMID- 17336230 TI - Spinal metastasis of occult lung carcinoma causing cauda equina syndrome. AB - Cauda equina syndrome (CES) may be caused by tumor, herniated disc, trauma and spinal infections. However, CES due to occult lung cancer has not been reported in the literature. A 50-year-old man presented with a subacute CES caused by an intradural metastasis of an adenocarcinoma of the lung to the lumbosacral cauda fibers. His lumbosacral magnetic resonance imaging (MRI), showed a well demarcated, intradural extramedullary mass lesion resembling a neurinoma at the L4/5 level. The patient underwent an L4-L5 laminectomy. The operative findings were also suggestive of neurinoma with involvement of three nerve roots, and a well-demarcated tumor without infiltration into the subarachnoid space. Although the findings of the operation were suggestive of neurinoma, final pathological diagnosis revealed metastatic carcinoma. Immunohistochemistry revealed clear cell adenocarcinoma metastasis. Chest X-ray and high resolution contrasted pulmonary computed tomography were normal. Positron emission tomography (PET) showed a lung mass, at the left apex. The patient was treated with chemotherapy and post operative spinal radiotherapy was also performed. The CES resolved after the operation and the patient was followed up for 2 years with no recurrence. MRI of intradural cauda equina metastasis may be similar to that of intradural nerve sheath tumor. Surgery and postoperative radiotherapy may be effective for the treatment of CES due to lung carcinoma. Definitive diagnosis is by histopathological examination with immunohistochemistry. If the primary cancer cannot be detected by conventional radiological techniques, PET may be helpful. PMID- 17336233 TI - Anatomy of the lymphatics. AB - The lymphatic system is perhaps the most complicated system of Homo sapiens. An introduction to the anatomy, embryology, and anomalies of the lymphatics is presented. The overall anatomy and drainage of the lymphatic vessels in outlined. The topographic anatomy, relations, and variations of the principle vessels of the lymphatic system (the right lymphatic duct, the thoracic duct, and the cisterna chyli) are presented in detail. PMID- 17336234 TI - Pathological evaluation of sentinel lymph nodes. AB - The sentinel lymph nodes are the most likely site of nodal metastasis. Their focused analysis results in upstaging cancers, although the extra yield from a more intensive work-up is generally dominated by micrometastases and isolated tumor cells. Nodal staging is generally done to reflect systemic spread of solid tumors and guide treatment accordingly. However, in general, the two processes of haematogenous and lymphogenic spread are not causally interrelated, and the extrapolation from low-volume nodal involvement to systemic involvement and therapeutic consequences of this extrapolation are still under investigation. PMID- 17336235 TI - Sentinel node mapping for melanoma: results of trials and current applications. AB - The value of sentinel node (SN) biopsy as a staging procedure and as a guide to prognosis with patients who have melanoma is now clearly established. As well, there is recent clinical trial evidence suggesting a survival benefit for patients found to be SN positive who have an immediate complete lymph node dissection (CLND), compared with those with nodal disease not treated by CLND until it becomes clinically apparent. Clinical trials are ongoing to determine whether CLND is necessary in all patients who are found to be SN positive. PMID- 17336236 TI - Sentinel node mapping for breast cancer: progress to date and prospects for the future. AB - Sentinel node biopsy (SNB) is indicated for women with small invasive breast cancers and clinically negative nodes. SNB indications are being expanded to larger breast tumors, some cases of ductal carcinoma in situ and selected clinically suspicious nodes. Because SNB has fewer and less severe complications than axillary lymph node dissection, physicians are exploring more ways it can be used to improve breast cancer treatment. The future of SNB includes resolution of the optimal timing of SNB in relation to neoadjuvant chemotherapy and the results of NSABP B-32 and ACOSOG Z10 and Z11. SNB has become the new standard of care for the treatment of early breast cancer. PMID- 17336237 TI - Sentinel node for gastrointestinal malignancies. AB - Sentinel node (SN) concept is valid in gastrointestinal (GI) malignancies. The dual tracer method with radio-guided and dye-guided SN mapping is feasible in GI malignancies and is useful in detecting unexpected aberrant drainage routes from GI cancers. SN mapping enabled us to perform individualized and step-wise lymphadenectomy in patients with GI cancer. A combination of SN mapping and endoscopic surgery will contribute to the improvement in quality of life after surgical treatment of GI cancer. PMID- 17336238 TI - Head and neck squamous cell carcinoma: sentinel node or selective neck dissection. AB - Improved knowledge about the metastatic behavior of mucosal squamous cell cancer of the head and neck made it possible to reduce the extension of elective and even therapeutic neck dissections by sparing selected levels, thereby reducing morbidity. The diagnostic question of when to treat a clinically negative neck to avoid unnecessary overtreatment, even through selective neck dissections, might be answered with sentinel lymph node biopsy. A thorough and sophisticated evaluation of this technique is necessary when defining suited patients. PMID- 17336239 TI - Safe introduction of new procedures and emerging technologies in surgery: education, credentialing, and privileging. AB - Ongoing horizon scanning is needed to identify new procedures and emerging technologies that should be evaluated for introduction into surgical practice. Following evidence-based evaluation, if a new modality is found ready for adoption in practice, surgeons need education in the safe and effective use of the new modality. The educational experience should include structured teaching and learning, verification of new knowledge and skills, preceptoring or proctoring, and monitoring of outcomes. Credentialing and privileging to perform a new procedure or use an emerging technology should be based on evaluation of knowledge and skills and outcomes of surgical care, and not merely on the numbers of procedures performed. Education of the entire surgical team is also essential. The entire process involving education, verification of knowledge and skills, credentialing, and privileging must be transparent. Patients need to play a central role in making informed decisions regarding their care that involves use of a new procedure or an emerging technology, and they should participate actively in their perioperative care. PMID- 17336240 TI - Lymph node dissection in surgical treatment of esophageal neoplasms. AB - The optimal lymphadenectomy for esophageal cancer remains controversial. The choice of surgical access determines to a great extent the type of lymphadenectomy possible. En bloc resections and three-field lymphadenectomy are concepts pioneered in the West and East, respectively; both should be performed in specialized centers because such extended lymph node dissection has substantial morbidity rates. Recent focus in research is on refining the indications for these procedures. Patient management strategies should be individualized. PMID- 17336241 TI - Gastric cancer: D2 dissection or low Maruyama Index-based surgery--a debate. AB - This article provides perspectives on the surgical approaches required optimally to manage patients with respectable gastric adenocarcinoma. The status of techniques of surgical resection in the management of gastric cancer is reviewed. The premise of this approach is that extended gastrectomy with D2 lymph node dissection is good. Also addressed are prognostic and predictive factors in the surgical treatment of stomach cancer. PMID- 17336242 TI - Pancreaticoduodenectomy with extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma. AB - Surgical resection provides the only chance for long-term survival for patients diagnosed with pancreatic and other associated periampullary adenocarcinomas. In the past, it had been suggested that the performance of an extended lymphadenectomy in association with a pancreaticoduodenal resection might have improved long-term survival for some patients. In response, six prospective trials have been performed and reported addressing this issue. These studies, including a large randomized trial of 280 patients from Johns Hopkins University, indicate that there is no demonstrable survival benefit to extended lymphadenectomy for periampullary cancer. PMID- 17336243 TI - Total mesorectal excision and pelvic node dissection for rectal cancer: an appraisal. AB - Total mesorectal excision has revolutionized the surgical treatment of rectal cancer since its introduction in the 1980s. The rationale, technique, and outcomes of total mesorectal excision in rectal cancer are explored. Lateral pelvic lymph node dissection is used by the Japanese in selected patients and has remained a controversial approach in the management of rectal cancer. The technique, controversies, and outcomes are summarized. PMID- 17336244 TI - Retroperitoneal lymph node dissection in testicular cancer. AB - With long-term survival in excess of 90% across all stages, testicular cancer has come to represent the model for successful multidisciplinary cancer care. Retroperitoneal lymph node dissection (RPLND) remains an integral component of testis cancer management strategies for both early- and advanced-stage disease. Commensurate with improvements made in clinical staging and in our understanding of the natural history of testis cancer, lymphatic spread, and neuroanatomy, considerable modifications in the technique and template of RPLND have taken place. The morbidity of primary RPLND and postchemotherapy RPLND is low when performed by experienced surgeons. This article reviews the evolution, role, and technique of RPLND in contemporary practice. PMID- 17336245 TI - Radical lymph node dissection for gallbladder cancer: indications and limitations. AB - Radical lymph node dissection provides survival benefit for patients with pT2 or more advanced gallbladder carcinoma tumors only if potentially curative resection is feasible; it must always be considered when planning a resection or re resection for robust patients with pT2 or more advanced gallbladder carcinoma tumors. The degree of radical lymphadenectomy depends on clinically assessed nodal status: portal lymph node dissection is limited to cN0 disease; extended portal nodal dissection is indicated for cN0 and a modest degree of cN1 disease; peripancreatic lymph node dissection with pancreaticoduodenectomy is indicated for selected cases of evident peripancreatic nodal disease and/or direct organ involvement. Extended resection with extensive lymphadenectomy should be limited to expert surgeons because it may cause serious morbidity and mortality. PMID- 17336246 TI - Radical cystectomy with an extended pelvic lymphadenectomy: rationale and results. AB - Lymphadenectomy at the time of cystectomy for muscle invasive bladder cancer offers, at worst, staging and prognostic information, and, at best, improved survival or cure. This article assesses both the evidence to support performing a lymphadenectomy at the time of cystectomy and the extent of lymphadenectomy that should be performed. The minimum lymph node dissection that should be performed at the time of cystectomy for muscle invasive bladder cancer should include meticulous removal of all tissue in the internal iliac, external iliac, and obturator areas, extending to include the distal common iliac nodes and nodes medial to the internal iliac vessels. Whether more extensive dissections than this improve survival is not yet clear. PMID- 17336247 TI - Regional node dissection for melanoma: techniques and indication. AB - Because virtually all microscopic nodal disease left untreated in melanoma patients will progress to clinically apparent macroscopic nodal disease, there is worse prognosis with macroscopic nodal disease, and ineffective systemic treatment currently exists, one must be cautious in favoring an observation approach to the regional basin in patients with a positive sentinel lymph node (SLN) in the hopes of avoiding the potential morbidity of a therapeutic node dissection. In the few patients with untreated microscopic nodal disease, the prognosis will be significantly worsened. Until further data are available, melanoma patients with a positive SLN by H&E analysis should proceed to a complete lymph node dissection. PMID- 17336248 TI - Selection of keynote addresses presented at the Acute Leukemia Forum 2006. March 31, 2006. San Francisco, California, USA. PMID- 17336249 TI - The chronic myeloproliferative disorders and mutation of JAK2: Dameshek's 54 year old speculation comes of age. AB - In 1951, William Dameshek speculated on the common origin of the chronic myeloproliferative disorders--polycythemia vera (PV), essential thrombocythemia (ET), chronic idiopathic myelofibrosis (IMF), and chronic myelogenous leukemia (CML). Subsequent work suggested that all arose from the hematopoietic stem cell. About 20 years ago the oncogene responsible for CML, bcr-abl, was identified, and more recently the mutant genes that cause hypereosinophilic syndrome and systemic mast cell disorder have been discovered. However, until very recently, the origin of PV, ET, and IMF have defied molecular explanation. In 2005, four separate groups working on tyrosine kinase signal transduction reported a gain-of function, valine-to-phenyalanine, mutation at position 617 in the JH2 domain of the Janus kinase (JAK) 2 cytoplasmic tyrosine kinase. This mutation requires the presence of the erythropoietin, thrombopoietin, or granulocyte-colony stimulating factor receptor/s for function, the mutation leads to functional hyperactivity and appears responsible for hematopoietic growth factor hypersensitivity, the most characteristic finding in these disorders. Virtually all patients with PV and substantial proportions of those with ET and IMF have now been shown to harbor this mutation. The mutant kinase appears to be a useful diagnostic test for myeloproliferative disorders and may have prognostic value. Future research will undoubtedly focus on the development of specific inhibitors as therapeutic agents as well as answering a number of questions that remain regarding the role of signal intensity, genotypic and phenotypic expression and the possible involvement of additional as yet unidentified mutations in these disorders. PMID- 17336250 TI - The leukemic stem cell. AB - Malignant stem cells have recently been described as the source of several types of human cancer. These unique cell types are typically rare and possess properties that are distinct from most other tumor cells. The properties of leukemic stem cells indicate that current chemotherapy drugs will not be effective. The use of current cytotoxic agents is not effective in leukemia because the agents target both the leukemic and normal stem cell populations. Consequently, new strategies are required that specifically and preferentially target the malignant stem cell population, while sparing normal stem cells. Several well known agents are lethal for the leukemic stem cell in preclinical testing. They include parthenolide, commonly known as feverfew, and TDZD-8. They have undergone various levels of preclinical development, but have not been used in patients as yet in the cancer setting. These drugs and combinations of existing therapies that target the leukemic stem cell population may provide a cure in this disease. This article summarizes recent findings in the leukemic stem cell field and discusses new directions for therapy. PMID- 17336252 TI - Is secondary leukemia an independent poor prognostic factor in acute myeloid leukemia? AB - Secondary leukemia is a poorly defined term that often refers to the development of acute myeloid leukemia (AML) following the history of a previous disease, such as a myelodysplastic syndrome or a chronic myeloproliferative disorder. Secondary leukemia can also be a consequence of treatment with chemotherapy, including alkylating agents and topoisomerase II inhibitors, and/or radiotherapy, or due to exposure to environmental carcinogens. Outcomes for this large and variable group of patients with secondary AML have been poor compared to people who develop AML de novo. The question arises whether a diagnosis of secondary leukemia per se indicates a poor prognosis or whether their bad outcomes result from an association with certain morphologic and biologic characteristics. Morphologic dysplasia in de novo AML is related to unfavorable cytogenetics, but has no independent prognostic relevance under the conditions of intensive chemotherapy. While there is no significant correlation between cytogenetic risk groups and dysplasia, cytogenetic features do have an impact on outcome among both de novo and secondary AML patients. In various subgroups of secondary AML, the spectrum of cytogenetic abnormalities is similar to de novo AML, but the frequency of abnormalities associated with unfavorable and intermediate risk cytogenetics, such as a complex karyotype, trisomy 8, monosomy 7, and others, is higher in secondary AML. The survival of patients with therapy-related myeloid leukemia (t AML) is generally shorter than for those with de novo AML within the same cytogenetic risk group. Across the population of t-AML, however, survival varies according to cytogenetic risk group, with longer survival in patients with favorable-risk karyotypes. The term secondary AML is too broad and imprecise to be of importance and should not be used. These AML patients should be enrolled on front-line chemotherapy trials and should be stratified by pretreatment disease status and exposure history, if necessary. Most importantly, the molecular and genetic differences that appear to determine the phenotype and the outcome of these patients need to be investigated further. PMID- 17336251 TI - The stem cell niche in health and leukemic disease. AB - That adult stem cells live in a highly specialized complex microenvironment, also known as a niche, is a pedestrian concept about 30 years old. It may, however, represent a relatively novel approach to being able to modify either normal or abnormal stem cells. Our emphasis in the past has been focused on identifying autonomous regulators of the stem cells and in attempting to modify them through the use of exogenous agents like cytokines. The body modulates these cells largely through the complex system that is embodied in the niche. This report discusses studies in which the niche components are modified to observe their effect on stem cells. The niches being investigated lie in the gut, skin, brain and bone. Other sites for hematopoiesis exist in the body, but these specific microenvironments can be localized and each component can be carefully evaluated using mouse models. Studies are ongoing as to how the stem cell microenvironment can support or propagate malignancies. By understanding the signals of this particular microenvironment, we may be able to adapt them to achieve a therapeutic benefit. PMID- 17336253 TI - Targeted agents in AML: much more to do. AB - To what degree has targeted therapy succeeded in acute myeloid leukemia (AML)? Targeted therapy has become a buzzword, with its meaning lost from overuse. In chronic myeloid leukemia (CML), gastrointestinal stromal cell tumor, and a small subset of patients with non-small cell lung cancer, a validated target has been identified and a highly specific therapeutic agent has been developed. Targeted therapy generally requires a pathophysiological Achilles heel in a tumor that can be exploited by nontoxic therapy. In most cases, the validated target has been a tyrosine kinase enzyme critical for tumor growth and survival. Are similar "drugable" targets available in AML? While our understanding of the pathophysiology of AML has advanced over the past decade, and some potential targets have been identified, no single agent will likely produce a significant proportion of remissions. On the other hand, nascent attempts with mild success have been achieved, yielding hope that this strategy will bear real fruit in the future. PMID- 17336254 TI - Myelodysplasia: the good, the fair and the ugly. AB - The myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders. The molecular pathogenesis of the disease is poorly understood and a large number of fundamental biologic questions remain. This heterogeneity presents challenges in selecting therapy for individual patients as well as for evaluating response to treatment. Only a small number of randomized clinical trials have been conducted, although three new drugs (azacitidine, lenalidomide, and decitabine) have been approved for use in the last few years. Response to most therapies occurs slowly, and sometimes months elapse before response can be evaluated. The response rates for most drugs used or studied for MDS range from <10%-20%. Some therapies seem more promising than others: immunosuppression with antithymocyte globulin results in extended durations of benefit in responders; lenalidomide induces a very high erythroid response rate in patients with del 5q- karyotype. The DNA hypomethylating agents, azacitidine and decitabine, can be of significant benefit for a fraction of patients and further investigation is needed to determine whether higher response rates occur in particular subgroups of MDS patients. Further refinements of dose and schedule of administration are also under investigation. PMID- 17336255 TI - Treatment of relapsed or refractory acute promyelocytic leukemia. AB - Current treatment for acute promyelocytic leukemia (APL) usually includes an induction phase with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy, followed by a consolidation phase of anthracycline-based chemotherapy and maintenance therapy with ATRA with or without low-dose chemotherapy for 1-2 years. This treatment strategy results in a high complete remission (CR) rate of about 90% and an overall survival rate of 80%. About 5% 30% of patients relapse, mainly patients with high-risk APL. Relapse at extramedullary sites, which occurs in approximately 3%-5% of patients, is emerging as a new issue. Treatment of relapsed/advanced APL includes the use of arsenic trioxide (ATO), gemtuzumab ozogamicin, and hematopoietic stem cell transplantation. ATO is currently the most effective therapeutic agent in relapsed APL. Hematopoietic stem cell transplantation is becoming a common strategy after achieving remission with ATO. Autologous transplant appears to have a more favorable outcome than allogeneic transplant in this setting, particularly when carried out during second remission, primarily because of significantly higher treatment-related mortality with allogeneic transplants. Allogeneic transplant, however, should be strongly considered for patients who remain molecularly positive. Future directions for APL therapy should include developing agents that can prevent relapse, particularly for high-risk patients. Other future treatment strategies may include use of ATO administered concomitantly or sequentially with chemotherapy, gemtuzumab or FLT-3 inhibitors that may obviate the need for autologous transplantation, and posttransplant maintenance perhaps with FLT-3 inhibitors. PMID- 17336256 TI - Hematopoietic cell transplantation from unrelated donors for treatment of patients with acute myeloid leukemia in first complete remission. AB - Hematopoietic cell transplantation from a histocompatible sibling is generally recommended for patients with acute myeloid leukemia in first remission with intermediate or high risk disease. Two-thirds of patients lack a matched sibling raising the question of the utility of matched unrelated transplantation for such patients. Retrospective studies from single institutions and registry data report 44-50% disease-free survival at 5-years following ablative unrelated donor transplantation for adults. The German AML 01/99 is the only prospective study evaluating the utility of matched related and unrelated transplantation for AML patients in first remission with high risk disease and reported 4-year survival of 68% with matched related transplants, 56% with matched unrelated transplants and 23% with autografting. Thus, results suggest that for patients with AML in first remission with high risk features (as determined by cytogenetics or >5% blasts on day 15 of induction) who lack matched siblings, unrelated donor transplantation should be considered. Current challenges are to improve our ability to identify those patients most likely to benefit from early transplantation, to better select donors, and to develop transplant preparative regimens that are safer and more effective. PMID- 17336257 TI - The role of autologous transplantation for acute myeloid leukemia in first and second remission. AB - Since 1986, the University of California San Francisco has developed novel approaches to autologous transplantation for acute myeloid leukemia (AML). Strategies have included intensive preparative regimens using busulfan and etoposide, and evolving strategies for pre-transplant consolidation and stem cell collection. Treatment-related mortality has been low (<5%), and after problems with slow engraftment and extended mucosal and skin toxicity in initial studies using 4-hydroperoxycyclophosphamide (4-HC)-purged bone marrow, peripheral blood autologous stem cell transplantation (ASCT) has been well tolerated even in older patients. In particular, careful attention to avoiding neurotoxicity associated with the use of high-dose cytarabine has limited dropout rates. Long-term event free survival (EFS) has been excellent in first remission (CR1) cytogenetically favorable groups, particularly with post-transplant treatment for acute promyelocytic leukemia (APL) patients with all-trans retinoic acid (ATRA; EFS 88%). ASCT in advanced disease showed overall long-term EFS of 44%; patients with APL in second remission achieved long-term EFS of 64%. Even among those failing primary induction, after remission induction with an alternative regimen, EFS was 61%. ASCT appears to be a treatment of choice for those in APL CR2, and offers some curative potential for AML CR2. The role of ASCT for those in CR1 is less clear, in part because high dropout rates in large randomized studies complicates interpretation of those studies. New directions for ASCT in the treatment of AML should focus on improving therapy, including calibrated intensification of induction regimens using plasma-kinetics targeting of dosages and the development and incorporation of immunotherapies into consolidation regimens. PMID- 17336258 TI - Can reduced-intensity allogeneic transplantation cure older adults with AML? AB - Development of nonablative and reduced-intensity conditioning regimens has enabled older or medically infirm patients with myeloid malignancies to be treated with allogeneic hematopoietic cell transplantation (HCT). These regimens rely largely on graft-versus-leukemia effects rather than high-dose therapy to eliminate malignant cells. Studies indicate that there is sustained engraftment with relatively low transplant-related mortality in the small number of patients who have been treated. This review summarizes the outcome in recent studies of patients with myeloid malignancies who received HCT following nonmyeloablative or reduced-intensity conditioning. Comparison of nonmyeloablative with myeloablative transplant shows that the myeloablative patients are about 10-15 years younger. Toxicity is a major problem in the elderly who have comorbid conditions, but otherwise the patient has a similar outcome, again emphasizing the graft-versus leukemia effect. Comparison of patients receiving related or unrelated grafts following nonmyeloablative conditioning shows that the outcome in these patients is similar. These studies have demonstrated encouraging overall survival and nonrelapse mortalities with evidence for graft-versus-leukemia responses in elderly patients with hematologic malignancies. Relapse and progressive disease continued to be problems, particularly in patients with large tumor burdens at time of HCT. Elimination of tumor burden prior to transplant with immunotherapy such as with radiolabeled anti-CD45 antibody or vaccines may improve outcome further. PMID- 17336259 TI - Novel strategies for the treatment and diagnosis of graft-versus-host-disease. AB - Graft-versus-host disease (GVHD) is a serious complication of hematopoietic stem cell transplantation. The main clinical targets of GVHD are the skin, liver, gastrointestinal tract, and possibly the lung. The standard initial therapy for GVHD includes the use of high-dose steroids, which result in an unsatisfactory complete response (CR) rate of about 40% and the need to develop more effective therapies. The Clinical Trial Network is conducting a four-arm randomized phase II study evaluating prednisone in combination with one of the following four agents: etanercept, mycophenolate mofetil, denileukin diftitox, and pentostatin. Etanercept, an anti-TNF-alpha antibody, is also being evaluated in combination with steroids in a single-center phase II trial at the University of Michigan because of the role of TNF-alpha in the pathogenesis of GVHD. TNF-alpha and a surrogate marker, soluble TNF receptor, are elevated in patients with GVHD as early as 7 days after transplantation and maybe used in the future as a prognostic tool to identify transplant recipients at risk for developing GVHD. PMID- 17336260 TI - New approaches to invasive fungal infections in acute leukemia and hematopoietic stem cell transplant patients. AB - Recognition and treatment of invasive fungal infections in acute leukemia and hematopoietic stem cell transplant patients are important clinical challenges. New diagnostic tools, such as fungal serologic assays and high-resolution CT scans, offer the hope for earlier initiation of antifungal therapy and improved treatment results. New antifungal agents offer choices that in some cases are less toxic than older drugs and in other cases are more efficacious. Combining the new diagnostic tools with new drugs, novel strategies are being evaluated to change our approaches to these deadly infections. PMID- 17336261 TI - Radiation-induced leukemia: lessons from history. AB - Beginning in 1895, with the discovery of x-rays, alpha and beta radiation, uranium, radium, thorium, and polonium, the fascinating story of the beginning of knowledge concerning the existence of ionizing radiation unfolds. This brief history of radiation and leukemia is divided into two main parts: the first 50 years, which deals with the confusion regarding radiation effects and the failure to clearly recognize that exposure to ionizing radiation may induce leukemia. The second part focuses on the last 60 years, when the radiation induction of leukemia was accepted and some progress achieved in understanding the clinical and pathophysiological characteristics of radiation-induced leukemia. Particular attention in this is paid to the effects of radiation on the survivors of Hiroshima and Nagasaki. The discussion in this section also covers some concepts of radiation-induced cell damage and ruminations on unanswered questions. PMID- 17336262 TI - Evaluation of splenomegaly in the hepatosplenic form of mansonic schistosomiasis. AB - This study was aimed to evaluate splenomegaly in patients with the hepatosplenic (HS) form of mansonic schistosomiasis (MS), analyzing the size and weight of the spleen and their relationships with patients' gender and age. Between October, 1993 to July, 1998, 78 patients with the HS form of MS had undergone splenectomy as treatment of choice for bleeding due to portal hypertension, at Hospital das Clinicas, Pernambuco, Brazil. By means of abdominal palpation, the excess spleen felt below the left costal edge was measured, and the weight was obtained after splenectomy along with the histopathological analysis. Liver biopsy was performed intraoperatively in order to confirm MS and to rule out other liver diseases. The mean age of the 78 patients were 45 years and 41 of them (53%) were female. The average spleen weight was 912g and the mean spleen size palpable below the left costal edge was 9.1cm. There was a positive relationship between size and weight (p<0.001). Spleen weight and size were larger in males (p=0.007 and p=0.001, respectively). An inverse correlation between age and spleen weight was observed (p<0.001). A classification based upon spleen weight showed 53% of patients presenting a moderate (501-1000g) and 33% a severe (>1001g) splenomegaly. As for the spleen size, the classification showed 64% of patients presenting moderate (4.1-10cm below the left costal edge) and 21% severe (>10cm) splenomegaly. In conclusion, splenomegaly may be considered a key physical finding in patients with HS form of MS, and we found a good correlation between the spleen sizes clinically evaluated with its weight. The majority of cases presents a moderate to severe splenomegaly and spleen size is larger in men and it seems to decrease with aging. PMID- 17336263 TI - Sample preparation for two-dimensional gel electrophoresis using pressure cycling technology. PMID- 17336264 TI - Characterization of heparin-living bacteria interactions by chemiluminescence electrophoretic mobility shift assay. PMID- 17336265 TI - NMR insights into dynamics regulated target binding of DLC8 dimer. AB - Conformational dynamics play a crucial role in biological function. Dynein light chain protein (DLC8) acts as a cargo adaptor, and exists as a dimer under physiological conditions and dissociates into monomer below pH 4. In the present NMR study, we identified some dynamic residues in the dimer using chemical shift perturbation approach by applying small pH change. As evidenced by gel filtration and CD studies, this small pH change does not alter the globular structural features of the protein. In fact, these changes result in small local stability perturbations as monitored using temperature dependence of amide proton chemical shifts, and influence the dynamics of the dimer substantially. Further, interaction studies of the protein with a peptide containing the recognition motif of cargo indicated that the efficacy of peptide binding decreases when the pH is reduced from 7 to 6. These observations taken together support the conception that dynamics can regulate cargo binding/trafficking by the DLC8 dimer. PMID- 17336266 TI - High-throughput magnetic resonance imaging in murine colonic inflammation. AB - The aim of this study was to investigate if a rapid magnetic resonance imaging (MRI) screening protocol (<5min/mouse) could characterize colonic inflammation in a chronic experimental colitis model. No respiratory triggering or spasmolytic agent was used during MRI-acquisition. Biomarkers assessed in vivo were colon wall thickness and T2w signal intensity (reflecting oedema) and ex vivo inflammatory score, colon weight, and plasma haptoglobin. The inflammation was characterised by significantly higher local and systemic inflammatory markers in the colitic mice compared to healthy mice. MRI-colon wall thickness and T2w signal intensity correlated well with inflammatory score (r=0.95 and 0.94), colon weight (r=0.92 and 0.93) and plasma haptoglobin (r=0.89 and 0.95). Thus, the data showed that in vivo MRI screening could be used to assess colon wall inflammation, suggesting that high-throughput MRI can be used to follow the potential efficacy of new IBD therapies in individual animal in longitudinal studies. PMID- 17336267 TI - Dynamic interplay between the neutral glycosphingolipid CD77/Gb3 and the therapeutic antibody target CD20 within the lipid bilayer of model B lymphoma cells. AB - The centroblast-specific differentiation marker CD77 (Gb(3)), is the receptor for Shiga-like toxin (SLT). The dynamic relationship between Gb(3)/CD77 and key B cell membrane proteins was studied in Burkitt's lymphoma cells with a focus on CD20. Engagement of Gb(3)/CD77 with SLT-B reduced the amount of CD20 and CXCR4 available, but levels of BCR, MHC Class II, CD21, CD27 and CD54 remained unchanged. Cholesterol depletion promoted a decrease in the number of sites accessed by CD20, CXCR4 and Gb(3)/CD77 antibodies. Constitutive localisation of Gb(3)/CD77 to lipid rafts was unperturbed by either SLT-B binding or cholesterol depletion, whereas the opposite was true for CD20. The effects were specific to SLT-B, highlighted by the inability of cholera toxin B-subunit to alter CD20 availability. Thus, the binding of Gb(3)/CD77 by its cognate ligand transmits information within the lipid bilayer of model lymphoma cells to impact the behaviour of selective proteins, most notably CD20, via a mechanism influenced by the level of cholesterol within the membrane. PMID- 17336268 TI - Immunohistochemical localization of D-alanine to beta-cells in rat pancreas. AB - A mouse monoclonal antibody against D-alanine (D-Ala) has been raised and the immunohistochemical localization of this D-amino acids in the rat pancreas is visualized. The obtained anti-D-Ala monoclonal antibody has no significant cross reactivity to all proteinogenic L-amino acids and their D-enantiomers. Using this antibody, immunohistochemical staining was performed on the pancreas, and specific staining for d-Ala has been observed only in the Langerhans islets. To identify the types of D-Ala-immunopositive cells, double staining was carried out with antibodies against D-Ala and pancreatic hormones. Similar immunostaining patterns have been observed for D-Ala and insulin, while D-Ala is hardly co localized with other hormones (glucagon, somatostatin, and pancreatic polypeptide). These results indicate for the first time that D-Ala is localized to insulin producing beta-cells in mammalian pancreas, suggesting that this D amino acid would be involved in the regulation of the blood glucose level. PMID- 17336269 TI - Characterization of membrane association of Rinderpest virus matrix protein. AB - Paramyxovirus matrix protein is believed to play a crucial role in the assembly and maturation of the virus particle by bringing the major viral components together at the budding site in the host cell. The membrane association capability of many enveloped virus matrix proteins has been characterized to be their intrinsic property. In this work, we have characterized the membrane association of Rinderpest virus matrix (M) protein. The M protein of Rinderpest virus when expressed in the absence of other viral proteins is present both in the cytoplasm and plasma membrane. When expressed as GFP fusion protein, the M protein gets localized into plasma membrane protrusions. High salt and alkaline conditions resulted in partial dissociation of M protein from cell membrane. Thus, M protein behaves like an integral membrane protein although its primary structure suggests it to be a peripheral membrane protein. PMID- 17336270 TI - Multidrug resistance protein 1 is not associated to detergent-resistant membranes. AB - Multidrug resistance protein 1 (MRP1) is a member of the ATP-binding cassette superfamily. Using the energy provided by ATP hydrolysis, it transports a broad spectrum of substrates across the plasma membrane, including hormones, leukotriene C(4), bile salts, and anti-cancer drugs. Recent works have suggested that P-glycoprotein is associated to cholesterol and sphingolipid-rich membrane microdomains and that cholesterol upregulates its ATPase and drug transport activities. Confocal microscopy experiments and Triton X-100 extraction of detergent-resistant membranes provide evidence that MRP1 is not located in raft like structures and that its activity is downregulated by cholesterol. The data are discussed in terms of cholesterol-protein interaction and topology. PMID- 17336271 TI - Flazinamide, a novel beta-carboline compound with anti-HIV actions. AB - A beta-carboline compound, flazin isolated from Suillus granulatus has been shown weak anti-HIV-1 activity. Based on the structure of flazin, flazinamide [1-(5'- hydromethyl-2'-furyl)-beta-carboline-3-carboxamide] was synthesized and its anti HIV activities were evaluated in the present study. The cytotoxicity of flazinamide was about 4.1-fold lower than that of flazin. Flazinamide potently reduced syncytium formation induced by HIV-1IIIB with EC50 value of 0.38muM, the EC50 of flazinamide was about 6.2-fold lower than that of flazin. Flazinamide also inhibited HIV-2ROD and HIV-2CBL-20 infection with EC50 values of 0.57 and 0.89microM, respectively. Flazinamide reduced p24 antigen expression in HIV-1IIIB acute infected C8166 and in clinical isolated strain HIV-1KM018 infected PBMC, with EC50 values of 1.45 and 0.77microM, respectively. Flazinamide did not suppress HIV-1 replication in chronically infected H9 cells. Flazinamide blocked the fusion between normal cells and HIV-1 or HIV-2 chronically infected cells. It weakly inhibited activities of recombinant HIV-1 reverse transcriptase, protease or integrase at higher concentrations. In conclusion, the conversion of the carboxyl group in 3 position of flazin markedly enhanced the anti-viral activity (TI value increased from 12.1 to 312.2) and flazinamide might interfere in the early stage of HIV life cycle. PMID- 17336272 TI - Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion. AB - CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment. PMID- 17336273 TI - Transplantation of bone marrow stromal cells containing the neurturin gene in rat model of Parkinson's disease. AB - The experiment was to evaluate the therapeutic benefit of transplanted bone marrow stromal cells (BMSCs) transfected with a kind of neurotrophic factor gene, neurturin (NTN) gene, in treating the rat model of Parkinson's disease (PD). The 6-OHDA-lesioned rats were assigned to one of three groups, those receiving BMSCs transfected with NTN gene, those receiving untransfected BMSCs containing a void plasmid and those receiving phosphate buffer solution (PBS). Treatments were injected into the right striatum (6-OHDA-lesioned side). One to six months post transplantation, apomorphine-induced rotational behavior was observed. One month after transplantation, green fluorescent protein (GFP)/NTN, GFP/glial fibrillary acidic protein (GFAP), GFP/neuron specific enolase (NSE) and GFP/tyrosine hydroxylase (TH) fluorescence determinations of brain sections were carried out. One to six months after transplantation, brain sections containing striatum and substantia nigra were stained for TH. In situ hybridization and Western blots were used to determine NTN mRNA and protein concentration, respectively, in affected brain regions. High performance liquid chromatography (HPLC) was used to measure the dopamine (DA) content in the lesioned striatum 1 and 3 month(s) post transplantation. The results were shown that: in the first 3 months after transplantation, the number of rotations was lower in NTN-transplant group than the void vector group, and during 1-6 months post-transplantation, the number of rotations was lower in both transplant groups than that in the PBS group (P<0.05). One month after transplantation, we detected GFP/NTN-, GFP/GFAP- and GFP/NSE-labeled cells in the transplantation area of the NTN-transplanted group, but no obvious GFP/TH labeled cells were found. Quantitative analysis of TH positive cells 1 to 6 months after transplantation indicated that there were no significant differences between groups in survival rates of TH-positive neurons in the lesioned substantia nigra (P>0.05). In situ hybridization and Western blot identified NTN mRNA and protein expression in the transplantation area of the NTN transplanted group. After transplantation of NTN-expressing cells, DA content in the lesioned striatum was significantly higher in the transgenic group than that in the void vector group or the PBS group (P<0.05). The overall therapeutic effects of the NTN-transplanted group were superior to those of the void plasmid group and the PBS group. The mechanisms by which transgenic therapy treats PD might involve functional enhancement of residual dopaminergic neurons by NTN, which significantly reduces the number of rotations in animals, but not increase the numbers of existing dopaminergic neurons. PMID- 17336274 TI - Distribution of glycinergic neuronal somata in the rat spinal cord. AB - Glycine transporter 2 (GlyT2) mRNA is exclusively expressed in glycinergic neurons, and is presently considered a reliable marker for glycinergic neuronal somata. In this study, we have performed non-radioactive in situ hybridization to localize GlyT2 mRNA in fixed free-floating sections of cervical (C2 and C6), thoracic (T5), lumbar (L2 and L5) and sacral (S1) segments of the rat spinal cord. The results showed that in all segments the majority of the GlyT2 mRNA labeled (glycinergic) neuronal somata was present in the deep dorsal horn and the intermediate zone (laminae III-VIII), with around 50% (range 43.7-70.9%) in laminae VII&VIII. In contrast, the superficial dorsal horn, the motoneuronal cell groups and the area around the central canal contained only few glycinergic neuronal somata. The density (number of glycinergic neuronal somata per mm(2)) was also low in these areas, while the highest densities were found in laminae V to VIII. The lateral spinal nucleus and the lateral cervical nucleus also contained a limited number of glycinergic neurons. Our findings showed that the distribution pattern of the glycinergic neuronal somata is similar in all the examined segments. The few differences that were found in the relative laminar distribution between some of the segments, are most likely due to technical reasons. We therefore conclude that the observed distribution pattern of glycinergic neuronal somata is present throughout the spinal cord. Our findings further showed that the non-radioactive in situ hybridization technique for identifying GlyT2 mRNA in fixed free-floating sections is a highly efficient tool for identifying glycinergic neurons in the spinal cord. PMID- 17336275 TI - Susceptibility of hippocampal neurons to Abeta peptide toxicity is associated with perturbation of Ca2+ homeostasis. AB - Neuritic dystrophy, loss of synapses and neuronal death in the cerebral cortex and hippocampus are hallmarks of Alzheimer's disease. The aim of the present study was to investigate the differential susceptibility of cortical and hippocampal neurons to amyloid-beta (Abeta)-induced toxicity. For that, we have used primary neuronal cultures prepared from rat brain cortex and hippocampus which were treated with the synthetic peptides Abeta25-35 or Abeta1-40. Abeta induced apoptotic cell death was analyzed by determining caspase-3-like activity. Neuritic dystrophy was evaluated by cobalt staining and MAP2 immunoreactivity. Perturbation of Ca(2+) homeostasis caused by exposure to Abeta was evaluated by determining basal cytosolic calcium levels in the whole neuronal population and by single cell calcium imaging under basal and KCl-depolarization conditions. Finally, levels of GluR2 subunit of glutamate AMPA (alpha-amino-3-hydroxy-5 methylisoxazole-4-proprionate) receptors were quantified by western blotting. Our results demonstrated that hippocampal neurons in culture are more susceptible than cortical neurons to Abeta-induced apoptosis and also that this mechanism involves the perturbation of Ca(2+) homeostasis. Accordingly, the exposure of hippocampal neurons to Abeta peptides decreases the protein levels of the GluR2 subunit of glutamate AMPA receptors that may be associated with a significant rise of cytosolic Ca(2+) concentration, leading to dendritic dystrophy and activation of apoptotic neuronal death. PMID- 17336276 TI - Nrf2-mediated protection against 6-hydroxydopamine. AB - Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by cell loss in the substantia nigra resulting in striatal dopamine depletion. Although the cause of sporadic PD is unknown, oxidative stress is thought to contribute to disease pathogenesis. One mechanism by which cells defend themselves against oxidative stress is through the transcriptional upregulation of cytoprotective genes. Under oxidative stress conditions, the transcription factor NF-E2-related factor (Nrf2) binds to the antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes. Here we show that loss of Nrf2-mediated transcription exacerbates vulnerability to the neurotoxin 6-hydroxydopamine (6-OHDA) both in vitro and in vivo. We further demonstrate that activation of the Nrf2-ARE pathway by the known chemical inducer tert-butylhydroquinone can protect against 6-OHDA in vitro. Induction of this pathway by transplantation of astrocytes overexpressing Nrf2 can protect against 6-OHDA-induced damage in the living mouse. This suggests that the Nrf2-ARE pathway is a promising target for therapeutics aimed at reducing or preventing cell death in PD. PMID- 17336277 TI - Stereological sex difference during development of the magnocelluar subdivision of the medial preoptic nucleus (MPN mag). AB - In Syrian hamsters, reproductive behaviors are initiated in the presence of appropriate hormonal and chemosensory cues. These cues are detected and integrated within a highly conserved pathway that converges on a small nuclear group in the lateral aspect of the medial preoptic area, the magnocellular subdivision of the medial preoptic nucleus (MPN mag). The MPN mag plays a critical role in the regulation of male mating behavior--bilateral ablation of the MPN mag eliminates copulation. The MPN mag is sexually differentiated in both neuron number and density, but not in overall volume or volume of individual neurons. The current study used unbiased stereological methods to determine when the MPN mag becomes sexually differentiated. Our data indicate that the MPN mag becomes sexually dimorphic in volume and cell number after the critical period when steroid treatment induces male sexual behavior. PMID- 17336278 TI - Taking ion channel degradation to heart. PMID- 17336279 TI - Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. AB - Thiobarbituric acid reactive substances (TBARS) and malondialdehyde (MDA) have been used as biomarkers of lipid oxidation for more than thirty years. The validity of these biomarkers has been rightfully criticized for a lack of specificity and problems with post sampling formation. Numerous assays have been published for their analysis giving rise to reference intervals for healthy non smoking humans varying more than to orders of magnitude. In spite of these problems, these biomarkers remain among the most commonly reported indices of oxidative damage and the present review focuses on the problems associated with MDA/TBARS analysis, their potential as biomarkers of oxidative stress and the effect of smoking on MDA status. PMID- 17336280 TI - Serum cystatin C as a better marker of vancomycin clearance than serum creatinine in elderly patients. AB - OBJECTIVES: The purpose of this study is to assess the usefulness of the concentration of cystatin C (Cys-C) in serum for predicting the clearance of vancomycin (CLvcm) compared with the serum concentration of creatinine (SCr) in the elderly. METHODS: Thirty-nine serum samples were obtained from 24 elderly patients (65 years and older). Creatinine clearance (CLcr) and the glomerular filtration rate calculated from the concentration of Cys-C (GFRcys-c) were estimated using Cockcroft & Gault's formula and Larsson's formula, respectively. RESULTS: The correlation constant for CLvcm and the reciprocal of Cys-C (p=0.883) was significantly higher than that for CLvcm and the reciprocal of SCr (p=0.575, p<0.005). GFRcys-c was strongly correlated with CLvcm (p=0.883) and the constant was significantly higher than that for the correlation between CLvcm and CLcr (p=0.684, p<0.05). These results suggest that the serum concentration of Cys-C is a more reliable marker for predicting CLvcm than is SCr in elderly patients. PMID- 17336281 TI - Trophic factor supplemented UW solution reduces intimal hyperplasia in the rat aortic transplant model. AB - BACKGROUND: Chronic allograft nephropathy (CAN) is associated with delayed graft function, cold ischemic injury, and is an important cause of premature graft loss. A characteristic vascular lesion of CAN is intimal hyperplasia (IH). The goal of this study was to evaluate the effect of cold storage in University of Wisconsin solution supplemented with trophic factors (UW-TF) on IH in rat aortic isograft (IG) and allograft (AG) models. METHODS: F344 --> F344 and Lewis --> F344 orthotopic abdominal aortic transplants were performed after 48 h of cold storage in either UW or UW-TF solution with and without immunosuppression. RESULTS: Significant reduction in IH was observed when IG were stored in UW-TF solution compared to UW solution. A significant reduction in intimal inflammation was observed in UW-TF stored, nonimmunosuppressed AG. In immunosuppressed recipients, AG stored in UW-TF solution evidenced significantly less IH compared to those stored in UW alone. CONCLUSIONS: UW-TF solution decreased IH in both alloindependent and dependent models. PMID- 17336283 TI - The acetyltransferase activity of Drosophila CBP is dispensable for regulation of the Dpp pathway in the early embryo. AB - The CBP protein is a transcriptional co-activator and histone acetyltransferase. Reduced expression of Drosophila CBP (dCBP) in the early embryo specifically impairs signaling by the TGF-beta molecules Dpp and Screw (Scw). This occurs by a failure to activate transcription of the tolloid (tld) gene, which codes for a protease that generates active Dpp and Scw ligands. We show that dCBP directly regulates this gene by binding to the tld enhancer, and that tld expression can be partially rescued with a dCBP transgene. At a slightly later stage of development, Dpp/Scw signaling recovers in mutant embryos, but is unable to turn on expression of the Dpp/Scw-target gene rhomboid (rho). Interestingly, an acetyltransferase (AT)-defective dCBP transgene rescued tld and rho gene expression to an extent comparable to the wild-type transgene, whereas a transgene containing a 130 amino acid deletion rescued tld but not late rho expression. A tracheal phenotype caused by the reduced dCBP levels was also rescued more efficiently with the wild-type dCBP transgene than with this mutant transgene. Our results indicate that separate parts of the dCBP protein are required on different promoters, and that the AT activity of dCBP is dispensable for certain aspects of Dpp signaling. We discuss the similarity of these results to the role of p300/CBP in TGF-beta signaling in the mouse. PMID- 17336282 TI - Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis. AB - Articular cartilage and synovial joints are critical for skeletal function, but the mechanisms regulating their development are largely unknown. In previous studies we found that the ets transcription factor ERG and its alternatively spliced variant C-1-1 have roles in joint formation in chick. Here, we extended our studies to mouse. We found that ERG is also expressed in developing mouse limb joints. To test regulation of ERG expression, beads coated with the joint master regulator protein GDF-5 were implanted close to incipient joints in mouse limb explants; this led to rapid and strong ectopic ERG expression. We cloned and characterized several mammalian ERG variants and expressed a human C-1-1 counterpart (hERG3Delta81) throughout the cartilaginous skeleton of transgenic mice, using Col2a1 gene promoter/enhancer sequences. The skeletal phenotype was severe and neonatal lethal, and the transgenic mice were smaller than wild type littermates and their skeletons were largely cartilaginous. Limb long bone anlagen were entirely composed of chondrocytes actively expressing collagen IX and aggrecan as well as articular markers such as tenascin-C. Typical growth plates were absent and there was very low expression of maturation and hypertrophy markers, including Indian hedgehog, collagen X and MMP-13. The results suggest that ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of GDF-5. PMID- 17336284 TI - Adapting an ambient monitoring program to the challenge of managing emerging pollutants in the San Francisco Estuary. AB - While over seven million organic and inorganic compounds that have been indexed by the American Chemical Society's Chemical Abstracts Service in their CAS Registry are commercially available, most pollution monitoring programs focus only on those chemical stressors for which regulatory benchmarks exist, and have been traditionally considered responsible for the most significant human and environmental health risks. Until the late 1990s, the San Francisco Estuary Regional Monitoring Program was no exception in that regard. After a thorough external review, the monitoring program responded to the need for developing a pro-active surveillance approach for emerging pollutants in recognition of the fact that the potential for the growing list of widely used chemical compounds to alter the integrity of water is high. We describe (1) the scientific and analytical bases underlying a new surveillance monitoring approach; (2) summarize approaches used and results obtained from a forensic retrospective; (3) present the growing data set on emerging pollutants from surveillance monitoring and related efforts in the San Francisco Bay Area to characterize newly targeted compounds in wastewater streams, sediment, storm water runoff, and biota; and (4) suggest next steps in monitoring program development and applied research that could move beyond traditional approaches of pollutant characterization. Based on the forensic analysis of archived chromatograms and chemical and toxicological properties of candidate compounds, we quantified a variety of synthetic organic compounds which had previously not been targeted for analysis. Flame retardant compounds, pesticides and insecticide synergists, insect repellents, pharmaceuticals, personal care product ingredients, plasticizers, non-ionic surfactants, and other manufacturing ingredients were detected in water, sediment, and/or biological tissue samples. Several of these compounds, especially polybrominated diphenyl ether flame retardants, exhibited concentrations of environmental concern. We also describe environmental management challenges associated with emerging pollutants and how pro-active surveillance monitoring might assist in implementing a more holistic approach to pollution prevention and control before emerging pollutants become a burden on future generations. PMID- 17336285 TI - Morphine-induced place preference: involvement of cholinergic receptors of the ventral tegmental area. AB - In the present study, the effects of intra-ventral tegmental area injections of cholinergic agents on morphine-induced conditioned place preference were investigated by using an unbiased 3-day schedule of place conditioning design in rats. The conditioning treatments with subcutaneous injections of morphine (0.5 7.5 mg/kg) induced a significant dose-dependent conditioned place preference for the drug-associated place. Intra-ventral tegmental area injection of an anticholinesterase, physostigmine (2.5 and 5 microg/rat) or nicotinic acetylcholine receptor agonist, nicotine (0.5 and 1 microg/rat) with an ineffective dose of morphine (0.5 mg/kg) elicited a significant conditioned place preference. Furthermore, intra-ventral tegmental area administration of muscarinic acetylcholine receptor antagonist, atropine (1-4 microg/rat) or nicotinic acetylcholine receptor antagonist, mecamylamine (5 and 7.5 microg/rat) dose-dependently inhibited the morphine (5 mg/kg)-induced place preference. Atropine or mecamylamine reversed the effect of physostigmine or nicotine on morphine response respectively. The injection of physostigmine, but not atropine, nicotine or mecamylamine, into the ventral tegmental area alone produced a significant place aversion. Moreover, intra-ventral tegmental area administration of the higher doses of physostigmine or atropine, but not nicotine or mecamylamine decreased the locomotor activity. We conclude that muscarinic and nicotinic acetylcholine receptors in the ventral tegmental area may critically mediate the rewarding effects of morphine. PMID- 17336286 TI - History of cocaine self-administration alters morphine reinforcement in the rat. AB - It has been shown repeatedly that cocaine pre-exposure may sensitise neurochemical and behavioural responses to opioid drugs. The aim of the present study was to investigate effects of a prior history of cocaine self administration on morphine reinforcement in the rat. Male Sprague-Dawley rats were allowed to acquire intravenous cocaine self-administration (0.3 mg/kg/infusion) for 20 days. When operant responding for cocaine had stabilised, morphine was introduced instead of cocaine in the next self-administration session. One group of cocaine-exposed rats was allowed to respond for 0.56 mg/kg/infusion of morphine (i.e. the dose which was willingly self-administered by drug-naive controls). The second group was allowed to respond for 0.056 mg/kg/infusion of morphine (i.e. the dose which did not maintain self administration behaviour in the drug-naive rats). The subjects with the history of cocaine self-administration, in contrast to the drug-naive group, did not maintain operant responding for 0.56 mg/kg/infusion of morphine. These rats easily self-administered the ten times lower dose of the opioid (0.056 mg/kg/infusion). An opioid receptor antagonist, naltrexone (1 mg/kg i.p.) restored the positive reinforcing properties of the higher dose of morphine in the cocaine-exposed rats. Concluding, the present results suggest that prior history of cocaine self-administration sensitises rats to the positive reinforcing properties of morphine. PMID- 17336287 TI - Atorvastatin modulates the profile of proteins released by human atherosclerotic plaques. AB - The mechanisms by which hydroxymethylglutaryl CoenzymeA reductase inhibitors (statins) reduce atherosclerotic cardiovascular morbidity and mortality remain poorly understood. Statins have been shown to modulate the levels of different inflammatory proteins both in carotid atherosclerotic plaques and in the blood of patients with atherosclerosis. In this work, we hypothesize that statins could also modulate the levels of the proteins secreted by cultured atherosclerotic plaques. Thus, the secretomes obtained from complicated atherosclerotic plaques incubated in the presence/absence of atorvastatin (10 micromol/l, 24 h) were analysed and compared by two-dimensional electrophoresis, considering the fibrous adjacent areas as controls. In total, 54 proteins (83 protein isoforms) were identified by Mass Spectrometry (MS): 24 proteins were increased and 20 proteins decreased in atheroma plaque supernatants compared to controls. Some of these proteins, like Cathepsin D, could play a significant role in plaque instability, becoming a potential target for therapeutical treatment. Interestingly, 66% of the proteins differentially released by atherosclerotic plaques reverted to control values after administration of atorvastatin, among them, Cathepsin D. Moreover, plaques obtained from patients who received atorvastatin treatment prior to carotid endarterectomy showed decreased Cathepsin D expression relative to plaques from non-treated patients. In conclusion, this proteomic approach has shown that statins are able to modulate the secretome of atherosclerotic plaques, and new therapeutical targets for statins have been characterised. PMID- 17336288 TI - Effects of the fatty acid amide hydrolase inhibitor URB597 on the sleep-wake cycle, c-Fos expression and dopamine levels of the rat. AB - Our group has described previously that the endogenous cannabinoid anandamide induces sleep. The hydrolysis of this lipid involves the activity of the fatty acid amide hydrolase (FAAH), which additionally catalyzes the degradation of the satiety factor oleoylethanolamide and the analgesic-inducing lipid palmitoylethanolamide. It has been demonstrated that the inhibition of the FAAH by URB597 increases levels of anandamide, oleoylethanolamide and palmitoylethanolamide in the brain of rats. In order to determinate the physiological properties of the FAAH inhibition on the sleep modulation, we report the pharmacological effects on the sleep-wake cycle of the rat after i.c.v. administrations of URB597, oleoylethanolamide or palmitoylethanolamide (10, 20 microg/5 microl). Separate unilateral i.c.v. injections of 3 compounds during the lights-on period, increased wakefulness and decreased slow wave (SW) sleep in rats in a dose-dependent fashion. We additionally found out that, compared to controls, c-Fos immunoreactivity in hypothalamus and dorsal raphe nucleus was increased in rats that received URB597, oleoylethanolamide or palmitoylethanolamide (10, 20 microg/5 microl, i.c.v.). Next, we found that after an injection of the compounds, levels of dopamine were increased whereas extracellular levels of levodopa (l-DOPA) were decreased. These findings indicate that that inhibition of the FAAH, via URB597, modulates waking. These effects were mimicked separately by the administration of oleoylethanolamide or palmitoylethanolamide. The alertness induced by the compounds tested here activated wake-promoting brain regions and they also induced the release of dopamine. Our results suggest that FAAH activity as well as two molecules that are catalyzed by this enzyme, oleoylethanolamide and palmitoylethanolamide, participate in the regulation of the waking state. Alternative approaches to treat sleep disorders such as excessive somnolence might consider the use of the URB597, oleoylethanolamide or palmitoylethanolamide since all compounds enhance waking. PMID- 17336289 TI - Raloxifene plus 17beta-estradiol inhibits proliferation of primary cultured vascular smooth muscle cells and human mammary endothelial cells via the janus kinase/signal transducer and activator of transcription3 cascade. AB - Long-term use of estrogen replacement therapy increases the risk of breast cancer. Presently, we investigated the effects and mechanisms of Raloxifene, a second generation selective estrogen receptor modulator, plus 17beta-estradiol on the proliferation of primary cultured vascular smooth muscle cells (VSMC) and human mammary endothelial cells (HMEC). Raloxifene plus 17beta-estradiol inhibited angiotensin II-induced VSMC proliferation and rapid phosphorylation of STAT(3); these effects were blocked by AG490, the janus kinase/signal transducer and activator of transcription3 (JAK/STAT(3)) inhibitor. STAT(3) production was not affected. In primary cultured HMEC, immunofluorescence identified the ERbeta subtype, but not the ERalpha subtype, in the nucleus. Raloxifene plus 17beta estradiol inhibited 17beta-estradiol-induced proliferation of HMEC. Western blot analysis established that Raloxifene attenuated the 17beta-estradiol-induced phosphorylation of STAT(3), and that this effect was blocked by AG490. We conclude that Raloxifene plus 17beta-estradiol inhibits the proliferation of VSMC and HMEC through the JAK/STAT(3) cascade, which in primary cultured HMEC may be implemented through ERbeta. PMID- 17336290 TI - Microtubule-stabilizing agent prevents protein accumulation-induced loss of synaptic markers. AB - Synaptic pathology is associated with protein accumulation events, and is thought by many to be the best correlate of cognitive impairment in normal aging and different types of dementia including Alzheimer's disease. Numerous studies point to the disruption of microtubule-based transport mechanisms as a contributor to synaptic degeneration. Reported reductions in a microtubule stability marker, acetylated alpha-tubulin, suggest that disrupted transport occurs in Alzheimer's disease neurons, and such a reduction is known to be associated with transport failure and synaptic compromise in a hippocampal slice model of protein accumulation. The slice model exhibits accumulated proteins in response to chloroquine-mediated lysosomal dysfunction, resulting in corresponding decreases in acetylated tubulin and pre- and postsynaptic markers (synaptophysin and glutamate receptors). To test whether the protein deposition-induced loss of synaptic proteins is due to disruption of microtubule integrity, a potent microtubule-stabilizing agent, the taxol derivative TX67 (10-succinyl paclitaxel), was applied to the hippocampal slice cultures. In the absence of lysosomal stress, TX67 (100-300 nM) provided microtubule stabilization as indicated by markedly increased levels of acetylated tubulin. When TX67 was applied to the slices during the chloroquine treatment period, pre- and postsynaptic markers were maintained at control levels. In addition, a correlation was evident across slice samples between levels of acetylated tubulin and glutamate receptor subunit GluR1. These data indicate that disruption of microtubule integrity accounts for protein deposition-induced synaptic decline. They also suggest that microtubule-stabilizing drugs can be used to slow or halt the progressive synaptic deterioration linked to Alzheimer-type pathogenesis. PMID- 17336291 TI - Pharmacological characterization of a chronic pruritus model induced by multiple application of 2,4,6-trinitrochlorobenzene in NC mice. AB - Female NC/Jic mice were sensitized and challenged repeatedly at 48 h intervals for 10 and 30 days by painting 1% 2,4,6-trinitrochlorobenzene (TNCB) on both ears. Mice challenged with TNCB for 30 days developed an inflammatory dermatitis with high immunoglobulin E (IgE) titer. Histological analysis with acidic Toluidine Blue staining revealed that dermal mast cells markedly differentiated and intensely degranulated, consistent with a dramatic increase in scratching behavior. A significant increase in total scratching events could be observed in mice treated with TNCB for a short period of 10 days. Extending the term of TNCB application to 30 days, the IgE titer and number of mast cells elevated significantly, and thus various drugs were evaluated pharmacologically by using the mice treated with TNCB for 30 days. Terfenadine and cyproheptadine attenuated the chronic scratching behavior. Tacrolimus and dexamethasone were less effective and cromolyn showed no effect. In addition, terfenadine and tacrolimus suppressed the degranulation of mast cells. The present chronic scratching model could be suitable to evaluate drugs effective for suppression of mast cell differentiation and degranulation by irritation, and may represent a promising tool to develop new drugs for inflammatory pruritus associated with, for example, atopic dermatitis. PMID- 17336292 TI - A dual antagonist for chemokine CCR3 receptor and histamine H1 receptor. AB - Eosinophilic chemokines and histamine play distinct but important roles in allergic diseases. Inhibition of both eosinophilic chemokines and histamine, therefore, is an ideal strategy for the treatment of allergic inflammation, such as asthma, allergic rhinitis, and atopic dermatitis. YM-344484 was found to potently inhibit both the CCL11-induced Ca2+ influx in human CCR3-expressing cells (Kb=1.8 nM) and histamine-induced Ca2+ influx in histamine H1 receptor expressing PC3 cells (Kb=47 nM). YM-344484 also inhibited the CCL11-induced chemotaxis of human CCR3-expressing cells (IC50=6.2 nM) and CCL11-induced eosinophil-derived neurotoxin release from human eosinophils (IC50=19 nM). Orally administered YM-344484 inhibited the increase in histamine-induced vascular permeability in mice (82% inhibition at a dose of 10 mg/kg) and the accumulation of eosinophils in a mouse asthma model (74% at a dose of 300 mg/kg). These results indicate that YM-344484, a novel and functional dual antagonist for chemokine CCR3 receptor and histamine H1 receptor, is an attractive candidate for development as a novel anti-allergic inflammation drug. PMID- 17336293 TI - Fluorescence lifetime imaging study of a thin protein layer on solid surfaces. AB - Understanding the fundamental interactions between proteins and solid surfaces is essential in the area of implantable medical devices. Fluorescence methods offer the sensitivity required to study the formation of the initial thin protein layers that mediate biocompatibility of materials. Thin protein layers (bovine serum albumin labelled with 1-anilino-8-naphthalenesulfonate, BSA-ANS) deposited on several surfaces (glass, silicon, stainless steel, polystyrene, and silver island film) were studied using confocal frequency domain Fluorescence Lifetime Imaging Microscopy (FLIM) and single-point multifrequency lifetime analysis techniques. FLIM provides spatial information about both fluorophores located on the surface and physicochemical parameters of the surface microenvironment. The average fluorescence lifetimes (tau(av)) of the adsorbed BSA-ANS generated by the contact between a protein solution and the material surface were measured by the multifrequency modulation and phase shift. Results indicate that tau(av) values of the albumin complexes on the surfaces (approximately 12 ns) are, in general, shorter than tau(av) found in the bulk solution (approximately 14 ns). For some surfaces, like polystyrene and silver island film the differences in tau(av) of the adsorbed BSA-ANS were found to be much greater. The differences in fluorescence lifetimes may indicate structural changes in the BSA protein induced by contact with the surface. PMID- 17336294 TI - A human anti-neuronal autoantibody against GABA B receptor induces experimental autoimmune agrypnia. AB - In the serum and cerebrospinal fluid of a patient with recurrent acute episodes of respiratory crises, autonomic symptoms and total insomnia (agrypnia), we identified a novel anti-neural complement fixing antibody directed against GABA(B) receptor (GABA(B)R). Patient purified IgG recognized a band of approximately 110 kDa on protein extracts of mouse cerebellum, cortex and brainstem and immunolabelled cultured Chinese hamster ovary (CHO) cells, transfected with human GABA(B)R1 and rat GABA(B)R2 receptors. Western blot analysis of transfected CHO homogenates showed the same band using both patient purified IgG and anti-GABA(B)R1 antibody. In order to verify the pathogenic role of these purified antibodies, we injected patient IgG intrathecally into cisterna magna of C57BL/6 mice pre-implanted with EEG electrodes and we observed severe ataxia followed by breathing depression and total suppression of slow wave sleep, as evidenced by EEG recording, in a dose-dependent manner. Immunohistochemistry on brain sections of mice injected with patient IgG showed the simultaneous presence of bound human IgG and C5b-9 deposits on Purkinje cells and cerebellar granular layer. After incubation with anti-GABA(B)R antibody, a marked reduction of receptor immunostaining was found with relative sparing of neuronal architecture. In conclusion we recognized an anti-neuronal autoantibody directed against GABA(B)R that is associated with autoimmune agrypnia and we showed that our patient purified IgG was able to induce in mice experimental autoimmune agrypnia characterized by a complex neurological syndrome affecting several CNS functions. PMID- 17336295 TI - Entamoeba histolytica: apoptosis induced in vitro by nitric oxide species. AB - Apoptosis has been described in some parasites like Leishmania, Trypanosoma, and Trichomonas. This phenomenon has not been observed yet in Entamoeba histolytica. This work analyzed the in vitro effect of sodium nitroprusside, sodium nitrite and sodium nitrate (NOs) on E. histolytica apoptosis. Parasites incubated for 1h with NOs revealed apoptosis 6h later (95% viability), demonstrated by YOPRO-1, TUNEL, DNA fragmentation and low ATP levels. The caspase inhibitor Z-VAD-FMK inhibited total intracellular cysteine protease activity (CPA) but had no effect on apoptosis. When treated with NOs some amebic functions like complement resistance and hemolytic activity decreased but CPA and erythrophagocytosis remained unchanged. After treatment in vitro with NOs, parasite death was almost complete at 24h; but when injected into hamster livers they disappeared in less than 6h. These results show that apoptosis is induced in vitro by NOs in E. histolytica and renders them incapable of surviving in hamster's livers. PMID- 17336296 TI - A non-radiolabeled heme-GSH interaction test for the screening of antimalarial compounds. AB - Intraerythrocytic Plasmodium produces large amounts of toxic heme during the digestion of hemoglobin, a parasite specific pathway. Heme is then partially biocristallized into hemozoin and mostly detoxified by reduced glutathione. We proposed an in vitro micro assay to test the ability of drugs to inhibit heme glutathione dependent degradation. As glutathione and o-phthalaldehyde form a fluorescent adduct, we followed the extinction of the fluorescent signal when heme was added with or without antimalarial compounds. In this assay, 50 microM of amodiaquine, arthemether, chloroquine, methylene blue, mefloquine and quinine inhibited the interaction between glutathione (50 microM) and heme (50 microM), while atovaquone did not. Consequently, this test could detect drugs that can inhibit heme-GSH degradation in a fast, simple and specific way, making it suitable for high throughput screening of potential antimalarials. PMID- 17336297 TI - Plasmodium yoelii: experimental evidences for the conserved epitopes between mouse and human malaria parasite, Plasmodium falciparum. AB - Bioinformatic analyses of gene homologues have revealed functionally conserved epitopes between human and rodent malaria parasites. Here, we present experimental evidence for the presence of functionally and antigenically conserved domains between Plasmodium falciparum and Plasmodium yoelii asexual blood-stages. Merozoite released soluble proteins (MRSPs) from both P. falciparum and P. yoelii bound to heterologous mouse or human red blood cells, respectively. The presence of conserved antigenic epitopes between the two species of parasites was evident by the inhibitory effect of antibodies, developed against P. yoelii in convalescent mice, on P. falciparum growth and merozoite reinvasion in vitro. Furthermore, mice immunized with P. falciparum MRSPs were protected from infection by a P. yoelii challenge. These data indicate that different species of Plasmodium contain antigenically conserved interspecies domains, which are immunogenic and, thus constitute a potential novel antigen source for vaccine development and testing using a mouse model. PMID- 17336298 TI - Plasmodium yoelii: influence of antimalarial treatment on acquisition of immunity in BALB/c and DBA/2 mice. AB - The effect of antimalarial drugs on immune responses to the malaria infection is evaluated in vivo using two experimental self-cured rodent models. BALB/c and DBA/2 mice were infected by Plasmodium yoelii 17XNL and 17XL strains, respectively, and then treated with different doses of antimalarial drugs: chloroquine (228mg/kg or 114mg/kg of the body weight) or artesunate (78mg/kg or 39mg/kg). The effect of antimalarial drugs on host immune responses was evaluated by parasitemia, splenocyte IFN-gamma production level, and parasite-specific IgG level in the serum, however, no significant differences were observed between drug-treated and untreated groups. Moreover, most of the infected mice of all groups showed the ability to resist homologous reinfection (challenged on day 60 post-infection), only a few mice experienced transient, low parasitemia. The rechallenged mice were accompanied by high level of parasite-specific IgG. Therefore, this research implicated that, for BALB/c and DBA/2 mice, chloroquine or artesunate treatment of blood-stage P. yoelii infections does not compromise acquired immunity to malaria in either primary infection or upon rechallenge. PMID- 17336299 TI - Plasmodium vivax: genetic diversity of the apical membrane antigen-1 (AMA-1) in isolates from India. AB - Malaria parasites exhibit sequence diversity for a number of stage specific antigens. Several studies have proved that apical membrane antigen-1 (AMA-1) is an effective target for eliciting a protective immune response in humans and other experimental animals. We have investigated the sequence variation in Plasmodium vivax AMA-1 (Pv AMA-1) from different Indian isolates. This is the first study of its kind for the nearly full length Pv AMA-1 from India. Our analysis reveals greater degree of genetic diversity in Pv AMA-1 than reported so far and identifies five novel haplotypes. This is significant to establish the antigenic repertoire of isolates in a malaria endemic country like India. PMID- 17336300 TI - Expression of rice Ca(2+)-dependent protein kinases (CDPKs) genes under different environmental stresses. AB - Ca(2+)-dependent protein kinases (CDPKs) play an essential role in plant Ca(2+) mediated signal transduction. Twenty-nine CDPK genes have been identified in the rice genome through a complete search of genome and full-length cDNA databases. Eight of them were reported previously to be inducible by different stress stimuli. Sequence comparison revealed that all 29 CDPK genes (OsCPK1-29) contain multiple stress-responsive cis-elements in the promoter region (1kb) upstream of genes. Analysis of the information extracted from the Rice Expression Database indicates that 11 of the CDPK genes are regulated by chilling temperature, dehydration, salt, rice blast infection and chitin treatment. RT-PCR and RNA gel blot hybridization were performed in this study to detect the expression 19 of the CDPK genes. Twelve CDPK genes exhibited cultivar- and tissue-specific expression; four CDPK genes (OsCPK6, OsCPK13, OsCPK17 and OsCPK25) were induced by chilling temperature, dehydration and salt stresses in the rice seedlings. While OsCPK13 (OsCDPK7) was already known to be inducible by chilling temperature and high salt, this is the first report that the other three genes are stress regulated. OsCPK6 and OsCPK25 are up-regulated by dehydration and heat shock, respectively, while OsCPK17 is down-regulated by chilling temperature, dehydration and high salt stresses. Based on this evidence, rice CDPK genes may be important components in the signal transduction pathways for stress responses. Findings from this research are important for further dissecting mechanisms of stress response and functions of CDPK genes in rice. PMID- 17336301 TI - Effects of aging on triggering receptor expressed on myeloid cells (TREM)-1 induced PMN functions. AB - Triggering receptor expressed on myeloid cell-1 (TREM-1) is a recently described receptor that has many effects on polymorphonuclear neutrophil (PMN), as the engagement of this receptor on PMN can induce phagocytosis, respiratory burst and degranulation. We studied the effects of aging on TREM-1 engagement in human PMN. PMN from elderly were found to have impaired response following TREM-1 engagement. Notably they were not able to modulate the TREM-1-induced respiratory burst as PMN from young did. TREM-1 engagement could not reverse PMN survival following incubation with LPS or GM-CSF in the elderly whereas it did in the young. The phosphorylation of TREM-1 signal transduction molecules was altered with aging. Finally, TREM-1 engagement could not drive the recruitment of TREM-1 in the lipid-rafts of the elderly explaining in part the altered response. The observed alterations in TREM-1 response are possibly an important contributing factor in the higher incidence of sepsis-related deaths in the elderly population. PMID- 17336302 TI - Gene expression of cyclin-dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 but not by the related proteins p63 or p73. AB - Cks2 proteins are essential components of cyclin/cyclin-dependent kinase complexes and contribute to cell cycle control. We identify Cks2 as a transcriptional target downregulated by the tumor suppressor p53. Cks2 expression was found to be repressed by p53 both at the mRNA and the protein levels. p53 downregulates transcription from the Cks2 promoter in a dose-dependent manner and in all cell types tested. This repression appears to be independent of p53 binding to the Cks2 promoter. In contrast to p53, neither p63 nor p73 proteins can repress Cks2 transcription. Thus p53, rather than its homologues p63 and p73, may contribute to control of the first metaphase/anaphase transition of mammalian meiosis by downregulation of Cks2 expression. PMID- 17336303 TI - The sulfhydryl oxidase Erv1 is a substrate of the Mia40-dependent protein translocation pathway. AB - The thiol oxidase Erv1 and the redox-regulated receptor Mia40/Tim40 are components of a disulfide relay system which mediates import of proteins into the intermembrane space (IMS) of mitochondria. Here we report that Erv1 requires Mia40 for its import into mitochondria. After passage across the translocase of the mitochondrial outer membrane Erv1 interacts via disulfide bonds with Mia40. Erv1 does not contain twin "CX(3)C" or twin "CX(9)C" motifs which are crucial for import of typical substrates of this pathway and it does not need two "CX(2)C" motifs for import into mitochondria. Thus, Erv1 represents an unusual type of substrate of the Mia40-dependent import pathway. PMID- 17336304 TI - Comparative endocrinology of testicular, adrenal and thyroid function in captive Asian and African elephant bulls. AB - Concentrations of serum testosterone, cortisol, thyroxine (free and total T4), triiodothyronine (free and total T3) and thyroid stimulating hormone (TSH) were measured to assess adrenal and thyroid function as they relate to testicular activity and musth in captive elephants. Blood samples were collected approximately weekly from Asian (n=8) and African (n=12) bulls at seven facilities for periods of 4 months to 9.5 years. Age ranges at study onset were 8 50 years for Asian and 10-21 years for African elephants. Based on keeper logs, seven Asian and three African bulls exhibited behavioral and/or physical (temporal gland secretion, TGS, or urine dribbling, UD) signs of musth, which lasted 2.8+/-2.5 months in duration. Serum testosterone was elevated during musth, with concentrations often exceeding 100 ng/ml. Patterns of testosterone secretion and musth varied among bulls with no evidence of seasonality (P>0.05). Only three bulls at one facility exhibited classic, well-defined yearly musth cycles. Others exhibited more irregular cycles, with musth symptoms often occurring more than once a year. A number of bulls (1 Asian, 9 African) had consistently low testosterone (<10 ng/ml) and never exhibited significant TGS or UD. At facilities with multiple bulls (n=3), testosterone concentrations were highest in the oldest, most dominant male. There were positive correlations between testosterone and cortisol for six of seven Asian and all three African males that exhibited musth (range, r=0.23-0.52; P<0.05), but no significant correlations for bulls that did not (P>0.05). For the three bulls that exhibited yearly musth cycles, TSH was positively correlated (range, r=0.22-0.28; P<0.05) and thyroid hormones (T3, T4) were negatively correlated (range, r=-0.25 to 0.47; P<0.05) to testosterone secretion. In the remaining bulls, there were no clear relationships between thyroid activity and musth status. Overall mean testosterone and cortisol concentrations increased with age for all bulls combined, whereas thyroid activity declined. In summary, a number of bulls did not exhibit musth despite being of adequate physical maturity. Cortisol and testosterone were correlated in most bulls exhibiting musth, indicating a possible role for the adrenal gland in modulating or facilitating downstream responses. Data were generally inconclusive as to a role for thyroid hormones in male reproduction, but the finding of discrete patterns in bulls showing clear testosterone cycles suggests they may facilitate expression or control of musth in some individuals. PMID- 17336305 TI - Characterisation of three variants of estrogen receptor beta mRNA in the common sole, Solea solea L. (Teleostei). AB - In all vertebrates, estrogen action is mediated by cognate nuclear receptors. In this study, we cloned the different transcripts of the estrogen receptor beta (ERbeta) gene of the common sole, Solea solea. 5'-RLM-RACE (RNA Ligase-Mediated 5'-Rapid Amplification of cDNA Ends) and 3'-RACE analyses revealed three isoforms of different length, called Long, Intermediate and Short isoforms, consisting of 2212, 1531 and 1207 b, respectively. The Long isoform is characterised by an open reading frame (ORF) encoding 589aa, with an estimated molecular weight of 65kDa. Phylogenetic analysis established that it belongs to the teleost ERbeta1 or ERbetaa cluster. The Intermediate isoform encodes a 490-aa protein, which lacks the first 99aa of the Long isoform, but still retains a complete DNA-binding domain (DBD). In the Short variant (363aa-long), all the N-terminal region, down to the two zinc fingers included, is missing, thus crippling DBD. ERbeta transcription was analysed by semiquantitative RT-PCR with specific primers, common to the Long and Intermediate isoforms, in various sole tissues, such as brain, gills, muscle, stomach, intestine, spleen, head kidney, kidney, liver and gonads. This analysis revealed that ERbeta displays a widespread or ubiquitous pattern of transcription, with the highest levels being found in the gonads and liver. PMID- 17336306 TI - Artificial neural network based fault identification scheme implementation for a three-phase induction motor. AB - This paper presents results from the implementation and testing of a PC based monitoring and fault identification scheme for a three-phase induction motor using artificial neural networks (ANNs). To accomplish the task, a hardware system is designed and built to acquire three-phase voltages and currents from a 1/3 HP squirrel-cage, three-phase induction motor. A software program is written to read the voltages and currents, which are first used to train a feed-forward neural network structure using the JavaNNS program. The trained network is placed in a LabVIEW based program formula node that monitors the voltages and currents online and displays the fault conditions and turns the motor off. The complete system is successfully tested in real time by creating different faults on the motor. PMID- 17336307 TI - Are nurses prepared to curb the tobacco epidemic in China? A questionnaire survey of schools of nursing. AB - BACKGROUND: Smoking prevalence among Chinese males is the highest in the world and its morbidity and mortality is growing. Previous studies suggested nurses are inadequately prepared to treat tobacco use and dependence. OBJECTIVES: To examine the inclusion and organization of tobacco control content in the undergraduate nursing curriculum of Hong Kong and Mainland China; and the smoking status of faculty and students. DESIGN: Cross-sectional survey. METHODS: Deans of 32 nursing schools in Hong Kong and China with an undergraduate programme (representing over 12000 students) completed a self-administered questionnaire. RESULTS: Most schools included the health hazards of tobacco (56.3-100%), but few covered tobacco cessation theory (31.3-62.5%), or behavioural (9.4-56.3%) and pharmacological (3.1-34.4%) interventions in the curriculum. Most curricula covered less than 1h of tobacco content per year of study. Nearly all schools (93.1%) reported smoking among faculty but only half reported access to smoking cessation programmes. CONCLUSIONS: This is the first known study to examine the extent of tobacco control education in the nursing curriculum in China. Results suggested deficiencies in the coverage and clinical practice in smoking and smoking cessation, and recommendations were made to strengthen the curriculum. PMID- 17336308 TI - Alcohol consumption, alcohol-induced flushing and incidence of acute myocardial infarction among middle-aged men in Japan--Japan Public Health Center-based prospective study. PMID- 17336309 TI - Inflammation, atherosclerotic burden and cardiovascular prognosis. AB - BACKGROUND: The aim of this study was to evaluate the impact of various inflammatory markers on atherosclerotic burden and cardiovascular prognosis. METHODS: In a prospective study 720 patients preceding coronary angiography were enrolled. In all patients carotid and leg arteries were examined using sonographic methods and C-reactive protein, fibrinogen, interleukin-18 (IL-18) and interleukin-6 have been determined. Patients were compared with regard to atherosclerotic burden: no clinically significant stenosis (N=57, 7.9%), coronary artery disease only (N=362, 50.3%), coronary artery disease with peripheral atherosclerosis (=multi-vascular atherosclerosis, N=301, 41.8%). RESULTS: Follow up data after a median of 6.5 years were available in 719 patients (99.9%), 75 patients (10.4%) died from cardiovascular causes. Presence of multi-vascular atherosclerosis, elevation of IL-18 and elevation of fibrinogen were independently related to cardiovascular death in a fully adjusted model Hazard ratio (95% confidence interval) 2.0 (1.2-3.5) for presence of multi-vascular atherosclerosis (P<0.01), 2.2 (1.2-3.9) for high fibrinogen (P<0.01) and 2.8 (1.6 4.9) for high IL-18 (P<0.0001)). Fibrinogen was achieved as independent predictor for both, mortality and atherosclerotic burden, whereas IL-18 was not related to atherosclerotic burden. CONCLUSIONS: IL-18 was an independent predictor for future cardiovascular death but was not associated with extent of atherosclerosis, whereas fibrinogen was independently related to cardiovascular death and extent of disease. PMID- 17336310 TI - Maternal smoking in pregnancy is associated with cholesterol development in the offspring: A 27-years follow-up study. AB - OBJECTIVE: To examine the associations of maternal smoking in pregnancy with development of cholesterol levels from childhood to adulthood. METHODS: Total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol were measured annually from 1975 to 1993 and in 2002 in 350 subjects aged 5-19 years at baseline who participate in a prospective cohort study. Pregnancy and birth data were obtained through questionnaires sent to the parents. RESULTS: Children of mothers who smoked in pregnancy showed a higher annual change in total cholesterol of 0.12 mmol/l per 10 years (95% confidence interval (CI): 0, 0.23) compared to children whose mothers did not smoke in pregnancy. Larger effect estimates were found in children with moderate overweight (0.39 mmol/l per 10 years (95% CI: 0.14, 0.63). HDL-cholesterol and LDL-cholesterol showed tendencies towards a decrease and increase, respectively, in children of mothers who smoked in pregnancy compared to children whose mothers did not smoke in pregnancy. Adjustment for potential confounders did not materially change the effect estimates. CONCLUSION: This study suggests for the first time that maternal smoking in pregnancy is associated with an increased rise in total cholesterol levels and a tendency towards an adverse lipoprotein profile in the offspring. PMID- 17336311 TI - On the use of computer assisted resolution of non-separable peaks in a congener specific polybrominated diphenyl ether capillary gas chromatographic analysis. AB - The use of computer assisted deconvolution for chromatographically not separated peaks in the analysis of polybrominated diphenyl ethers (PBDEs) by capillary gas chromatography (CGC) was studied. Twenty-two not separated clusters containing 48 overlapped PBDEs were registered in the separation of a sample containing 122 PBDE congeners on a semipolar poly(8%-phenyl-92%-dimethyl)siloxane column. There were only two clusters in which overlapped PBDEs differ in the number of bromine atoms {PBDE 126(5Br) co-elutes with 154(6Br) and PBDE 105(5Br) co-elutes with 144(6Br)} and therefore their mass spectra could be successfully used for deconvolution purposes. In 22 other clusters 46 isomeric PBDEs with identical mass spectra overlapped and for their resolution a computer assisted deconvolution procedure using a commercial available program was used. A published procedure for the estimation of minimum number of peaks in a peak cluster for which the data found by deconvolution are reliable, has been adapted. Using this procedure, for eight overlapped PBDE full peak data (single peak retention times and peak areas) were extracted. PMID- 17336312 TI - Protein adsorption and transport in agarose and dextran-grafted agarose media for ion exchange chromatography. AB - This work examines the relationship between the physical properties of agarose and dextran-grafted agarose cation exchangers and protein adsorption equilibrium and rates. Four different sulfopropyl (SP) matrices were synthesized using a neutral agarose base material--two based on a short ligand chemistry and two obtained by grafting 10 and 40kDa dextran polymers. The pore accessibility, determined by inverse size exclusion chromatography (iSEC) with dextran probes, decreases dramatically as a result of the combined effects of crosslinking, dextran grafting, and the introduction of ionic ligands, with pore radii decreasing from 19nm for the base matrix to 6.1nm for the 40kDa dextran-grafted SP-matrix. In spite of this reduction, while the adsorption isotherms were similar, protein uptake rates were greatly increased with the dextran-grafted SP matrices, compared to SP-matrices based on the short ligand chemistry. The effective pore diffusivities were 4-10 times higher than free solution diffusivity for the dextran-grafted matrices, indicating that the charged dextran grafts result in enhanced protein mass transfer rates. PMID- 17336313 TI - State of the art of shear driven chromatography. Advantages and limitations. AB - The present paper reports on the experimental difficulties encountered when trying to realize the full potential of shear-driven chromatography in nanochannels. While it theoretically offers the possibility to yield over 10,000 plates per centimetre in a few seconds, the practical realization of this potential requires a detector miniaturisation that is carried to the extreme combined with very high sampling rates. In the present study, a charge coupled device camera and a photomultiplier tube combined with pinhole were tested as detector. Despite the fact that the photomultiplier tube could offer a higher sampling rate and a better sensitivity, the charge coupled device turned out to be better suited for the current set-up because of inevitable problems with the stray-light transported through the glass channel wall. The chemistry of the separation surface was additionally studied getting more homogenous coating, thus higher separation efficiency. Having also carried out a number of mechanical improvements, it is now possible to measure separations at a distance of 8mm downstream from the injection point. This is four times further downstream than ever before while realizing a four components mixture separation in less than 1.5s, with a plate generation velocity of about 2000-7000 plates per second depending on the sample. PMID- 17336314 TI - Use of the kinetic plot method to analyze commercial high-temperature liquid chromatography systems. II. Practically constrained performance comparison. AB - Using a set of experimentally determined plate height data obtained on three commercial high-temperature HPLC supports, and evaluating their isocratic separation speed potential under the application of a set of instrumental constraints, a qualitative map of the practically achievable critical pair separation speed potential of high-temperature HPLC has been established. The obtained data show that the gain in separation speed is more strongly affected by the instrumental limitations in the high-temperature range than it is for the low temperatures. For the presently considered case of alkylbenzene separations, the potential gain in analysis time that can be obtained by going from T=30 to 120 degrees C in the presence of a typical set of instrumental limitations nevertheless remains of the order of a factor of 2-4. The study also shows that improvements on the instrumentation side (increased detector frequency, pumping flow rate, smaller extra-column volumes, ...) are indispensable to fully benefit from the high temperature advantages for all separations requiring less than 10,000 effective theoretical plates. PMID- 17336315 TI - On-line liquid chromatography-electrospray ionisation mass spectrometry for kappa carrageenan oligosaccharides with a porous graphitic carbon column. AB - Enzymatically digested oligosaccharides of kappa-carrageenans were separated on a porous graphitic carbon (PGC) column and characterised on-line by electrospray ionisation mass spectrometry (ESI-MS). Two different developing ions were applied. Among them ammonium hydrogencarbonate showed more eluting power as it should on normal anion-exchange stationary phases. The oligosaccharides were detected by ESI-MS as fully deprotonated oligosaccharides. PMID- 17336316 TI - Novel approach for developing urinary nucleosides profile by capillary electrophoresis-mass spectrometry. AB - A simple, rapid and efficient capillary electrophoresis-mass spectrometry (CE-MS) method was developed to analyze urinary nucleosides for the first time. The composition of CE buffer and MS parameters were systematically optimized. The optimum buffer was 150 mM acetic acid containing 15% methanol and 15% ethanol. The optimum MS parameters were: methanol containing 0.5% acetic acid was selected as the sheath liquid and the flow rate was 5 microL/min; the flow rate and temperature of drying gas were 6L/min and 150 degrees C, respectively; the pressure of nebulizing gas was 2 psig; and the fragmentor and ESI voltage were 100 V and 4000 V, respectively. Under the optimum CE-MS conditions, the urinary nucleosides were separated within 18 min. The linearity between the relative peak areas and the corresponding concentration of nine nucleosides markers were excellent. The limits of detection (S/N=3) of markers were 0.00862-3.82 nmol/mL. The optimum CE-MS method was applied to analyze urine from 20 bladder cancer patients and 20 healthy volunteers. Considering the standards of many nucleosides cannot be obtained, it is not the ratios of the concentrations of nucleosides to that of creatinine in the literatures, but the ratios of the relative peak area of nucleosides to the concentration of creatinine that used for pattern recognition. And, the statistical analysis result indicated this method was feasible. PMID- 17336318 TI - Nanometric morphological variation of zinc oxide crystals using organic molecules with carboxy and sulfonic groups. AB - The morphological variation of wurtzite-type zinc oxide (ZnO) grown on a substrate in basic aqueous solutions was investigated using a wide variety of organic molecules with carboxy and sulfonic groups. The effect of the organic molecules on the nanometric morphology was classified into several categories. Hexagonal plates exhibiting the (001) planes were obtained by a planarizing effect with the addition of citric, tartaric, and maleic acids, although acetic, salicylic, fumaric, and succinic acids exhibited no effects on the morphology. The production of nanograins was observed by a miniaturizing effect with the addition of a polymeric molecule with carboxy groups and an anionic surfactant with a sulfonic group. Mosaic structures composed of granular crystals and bundles consisting of fibrils elongated in a direction toward the c-axis were produced by the addition of bulky dye molecules having benzene rings and carboxy or sulfonic groups. The influence of the organic molecules was related to the number of the functional groups and the stereochemical structure. The findings of this study suggest that the adsorbability of the organic molecules depending on the chemical structure to the specific crystal faces is essential for the variation of the nanometric morphology. PMID- 17336317 TI - Highly effective removal of heavy metals by polymer-based zirconium phosphate: a case study of lead ion. AB - Zirconium phosphate (ZrP) has recently been demonstrated as an excellent sorbent for heavy metals due to its high selectivity, high thermal stability, and absolute insolubility in water. However, it cannot be readily adopted in fixed beds or any other flowthrough system due to the excessive pressure drop and poor mechanical strength resulting from its fine submicrometer particle sizes. In the present study a hybrid sorbent, i.e., polymer-supported ZrP, was prepared by dispersing ZrP within a strongly acidic cation exchanger D-001 and used for enhanced lead removal from contaminated waters. D-001 was selected as a host material for sorbent preparation mainly because of the Donnan membrane effect resulting from the nondiffusible negatively charged sulfonic acid group on the exchanger surface, which would enhance permeation of the targeted metal ions. The hybrid sorbent (hereafter denoted ZrP-001) was characterized using a nitrogen adsorption technique, scanning electron microscope (SEM), and X-ray diffraction (XRD). Lead sorption onto ZrP-001 was found to be pH dependent due to the ion exchange mechanism, and its sorption kinetics onto ZrP-001 followed the pseudo first-order model. Compared to D-001, ZrP-001 exhibited more favorable lead sorption particularly in terms of high selectivity, as indicated by its substantially larger distribution coefficients when other competing cations Na(+), Ca(2+), and Mg(2+) coexisted at a high level in solution. Fixed-bed column runs showed that lead sorption on ZrP-001 resulted in a conspicuous decrease of this toxic metal from 40 mg/L to below 0.05 mg/L. By comparison with D-001 and ZrP-CP (ZrP dispersion within a neutrally charged polymer CP), enhanced removal efficiency of ZrP-001 resulted from the Donnan membrane effect of the host material D-001. Moreover, its feasible regeneration by diluted acid solution and negligible ZrP loss during operation also helps ZrP-001 to be a potential candidate for lead removal from water. Thus, all the results suggested that ZrP 001 offers excellent potential for lead removal from contaminated water. PMID- 17336319 TI - Membrane potential across reverse osmosis membranes under pressure gradient. AB - Membrane potential measurement has been widely used for the characterization of ionic membranes such as ion-exchange membranes without solvent permeability. However, there have been few studies on membrane potentials across pressure driven processes such as reverse osmosis (RO) membranes with solvent permeability. In the present study, the membrane potential across RO membranes in NaCl and MgCl2 under the pressure gradient, DeltaP=0-0.3 MPa, was measured. The experimental results were analyzed by the theoretical model based on the Donnan equilibrium and the extended Nernst-Planck flux equation considering the pressure effect. The theoretical values agreed well with the experimental ones. This indicates that membrane potential is useful for characterizing the effective charge density of the active layer of RO membranes under pressure gradient. PMID- 17336320 TI - Postural change effects on infants' AB task performance: visual, postural, or spatial? AB - Smith and colleagues (Smith, L. B., Thelen, E., Titzer, R., & McLin, D. (1999). Knowing in the context of acting: The task dynamics of the A-not-B error. Psychological Review, 106, 235-260) demonstrated that 10-month-olds succeed on a Piagetian AB search task if they are moved from a sitting position to a standing position between A and B trials. These authors explained this result by suggesting that because the reach must be executed by different muscle forces from the standing position, an appropriate reach to B is programmed without the memory of the previous reach interfering with the current reach. In the main study reported here, the influences of postural and spatial factors are separated by adding a condition in which the table containing the hiding wells is moved up at the same time as the infant is shifted to standing, thereby allowing a postural change without a change in the spatial relations between the hand and hiding locations. Results showed that in both a standard control condition and the sitting-to-standing condition in which the table also moved up, performance was poor. Only in the sitting-to-standing condition in which the spatial relation between the hand and apparatus was altered were infants successful. These outcomes demonstrate that perseveration effects are likely to occur at the level of reach planning rather than at the level of execution, thereby narrowing the gap between explanations of improvements in AB performance with age that emphasize prefrontal maturation as opposed to improvements in reaching ability. PMID- 17336321 TI - Antibody internalization studied using a novel IgG binding toxin fusion. AB - Targeted therapy encompasses a wide variety of different strategies, which can be divided into direct or indirect approaches. Direct approaches target tumor associated antigens by monoclonal antibodies (mAbs) binding to the relevant antigens or by small-molecule drugs that interfere with these proteins. Indirect approaches rely on tumor-associated antigens expressed on the cell surface with antibody-drug conjugates or antibody-based fusion proteins containing different kinds of effector molecules. To deliver a lethal cargo into tumor cells, the targeting antibodies should efficiently internalize into the cells. Similarly, to qualify as targets for such drugs newly-discovered cell-surface molecules should facilitate the internalization of antibodies that bind to them. Internalization can be studied be several biochemical and microscopy approaches. An undisputed proof of internalization can be provided by the ability of an antibody to specifically deliver a drug into the target cells and kill it. We present a novel IgG binding toxin fusion, ZZ-PE38, in which the Fc-binding ZZ domain, derived from Streptococcal protein A, is linked to a truncated Pseudomonas exotoxin A, the preparation of complexes between ZZ-PE38 and IgGs that bind tumor cells and the specific cytotoxicity of such immunocomplexes is reported. Our results suggest that ZZ-PE38 could prove to be an invaluable tool for the evaluation of the suitability potential of antibodies and their cognate cell-surface antigens to be targeted by immunotherapeutics based on armed antibodies that require internalization. PMID- 17336322 TI - An improved protocol for generation of immuno-potent dendritic cells through direct electroporation of CD14+ monocytes. AB - In this study we demonstrate a novel protocol showing that electroporation of CD14+ monocytes directly isolated from blood with green fluorescent protein (GFP) RNA results in a 3-fold higher yield of antigen presenting dendritic cells (DCs) when compared to conventional methods employing immature DCs for electroporation. We further show a stable electroporation efficacy resulting in 60% of GFP positive cells. Expression of co-stimulatory molecules and maturation markers such as CD80, CD86, CD83 as well of the chemokine receptor 7 (CCR7) was found in 90% of the mature DCs. Importantly, production of IL-12p70 was 10 times higher in cells electroporated at the monocyte stage compared to cells electroporated at the immature DC stage. Stimulation of autologous naive lymphocytes by DCs electroporated at monocytes stage elicited proliferation of CD8+ T-cell with 7 fold increase in IFN-gamma release. Blocking of the MHC-Class I molecules significantly inhibited the IFN-gamma release, indicating that antigen presentation was MHC-Class I mediated. In summary, electroporation of CD14+ monocytes with RNA results in a high yield of antigen presenting DCs with high immuno-stimulatory capacity and antigen presentation on MHC-Class I molecules. This improved method may represent an attractive approach for RNA-based DC immunotherapy. PMID- 17336323 TI - A NOD/SCID tumor model for human ovarian cancer that allows tracking of tumor progression through the biomarker Sp17. AB - No experimental animal model employing a primary human ovarian carcinoma (OC) cell line is presently available that tracks the progression of this cell line with an identifiable marker. This hinders investigations related to developing new approaches for treating OC. Here, we describe the development of a tumor model in NOD/SCID mice for human OC that makes use of the endogenously expressed tumor specific sperm protein 17 (Sp17) cancer testis antigen. In this model, human SKOV-3 OC cell lines were intra-peritoneally seeded. Subsequently viable SKOV-3 cells were recovered from primary organ cell cultures from the liver ovaries, abdomen, and ascitic fluid, and their presence was confirmed by the detection of Sp17 mRNA by RT-PCR and Sp17 protein by immunocytochemistry and FACS analysis. When SKOV-3 tumor cells were administered intravenously the mice developed primarily lung tumor foci. This model makes it possible to evaluate new immunotherapeutic strategies for the treatment of human OC based on the biomarker Sp17. PMID- 17336324 TI - Seasonal changes in glycerol content and cold hardiness in two ecotypes of the rice stem borer, Chilo suppressalis, exposed to the environment in the Shonai district, Japan. AB - The rice stem borer, Chilo suppressalis, is divided into at least two ecotypes in Japan, the Shonai ecotype (SN) which is distributed in the northern part of Japan, and the Saigoku ecotype (SG) which is distributed in the southwestern region. Cold hardiness is positively correlated with the level of glycerol in both ecotypes. To investigate whether ecological distribution affects glycerol accumulation and cold hardiness development in these two ecotypes, overwintering larvae of the SN and SG ecotypes were concurrently exposed to the Shonai district. Obvious differences in the progress of glycerol accumulation and cold hardiness development in SN and SG larvae were found in early winter in the Shonai district. The levels of glycerol content and cold hardiness were low in October and high in January in both ecotypes, but those levels were different within this period (November and December) between ecotypes; the levels in SN larvae quickly reached their maximum, whereas, in SG larvae levels increased slowly. Under controlled conditions, the effect of the period of acclimation at 10 degrees C and subsequent low-temperature (5 degrees C) exposure on glycerol accumulation was investigated. These results indicated that glycerol accumulation in SN was stimulated by the progression of diapause termination, whereas a higher cumulative effect on glycerol production in SG was found when diapause was in a deep state. PMID- 17336326 TI - Pathology of Hematodinium infections in snow crabs (Chionoecetes opilio) from Newfoundland, Canada. AB - Bitter crab disease (BCD) of snow crabs, Chionoecetes opilio, is caused by a parasitic dinoflagellate, Hematodinium sp. The disease has shown an alarming increase in prevalence in the commercial fishery in eastern and northeastern areas of Newfoundland and Labrador since it was first recorded there in the early 1990s. We documented histopathological alterations to the tissues in snow crabs with heavy infections of Hematodinium sp. and during sporulation of the parasite. Pressure necrosis was evident in the spongy connective tissues of the hepatopancreas and the blood vessels in most organs. In heavy infections, little remained of the spongy connective tissues around the hepatopancreas. Damage to the gills varied; in some cases it was severe, particularly during sporulation, involving apparent thinning of the cuticle, loss of epithelial cells, and fusion of the membranous layers of adjacent gill lamellae. Affected lamellae exhibited varying degrees of distention with a loss of trabecular cells, hemocyte infiltrations, and swelling or "clubbing" along the distal margins. Large numbers of zoospores were located along the distal margins of affected lamellae suggesting that sporulation may cause a lysis or bursting of the thin lamellar cuticle, releasing spores. Pressure necrosis, due to the build up of high densities of parasites, was the primary histopathological alteration in most tissues. Hematodinium infections in the snow crab are chronic, long-term infections that end in host death, during sporulation of the parasite. PMID- 17336328 TI - Correct folding of the beta-barrel of the human membrane protein VDAC requires a lipid bilayer. AB - Spontaneous membrane insertion and folding of beta-barrel membrane proteins from an unfolded state into lipid bilayers has been shown previously only for few outer membrane proteins of Gram-negative bacteria. Here we investigated membrane insertion and folding of a human membrane protein, the isoform 1 of the voltage dependent anion-selective channel (hVDAC1) of mitochondrial outer membranes. Two classes of transmembrane proteins with either alpha-helical or beta-barrel membrane domains are known from the solved high-resolution structures. VDAC forms a transmembrane beta-barrel with an additional N-terminal alpha-helix. We demonstrate that similar to bacterial OmpA, urea-unfolded hVDAC1 spontaneously inserts and folds into lipid bilayers upon denaturant dilution in the absence of folding assistants or energy sources like ATP. Recordings of the voltage dependence of the single channel conductance confirmed folding of hVDAC1 to its active form. hVDAC1 developed first beta-sheet secondary structure in aqueous solution, while the alpha-helical structure was formed in the presence of lipid or detergent. In stark contrast to bacterial beta-barrel membrane proteins, hVDAC1 formed different structures in detergent micelles and phospholipid bilayers, with higher content of beta-sheet and lower content of alpha-helix when inserted and folded into lipid bilayers. Experiments with mixtures of lipid and detergent indicated that the content of beta-sheet secondary structure in hVDAC1 decreased at increased detergent content. Unlike bacterial beta-barrel membrane proteins, hVDAC1 was not stable even in mild detergents such as LDAO or dodecylmaltoside. Spontaneous folding of outer membrane proteins into lipid bilayers indicates that in cells, the main purpose of membrane-inserted or associated assembly factors may be to select and target beta-barrel membrane proteins towards the outer membrane instead of actively assembling them under consumption of energy as described for the translocons of cytoplasmic membranes. PMID- 17336327 TI - Dynamic requirements for a functional protein hinge. AB - The enzyme triosephosphate isomerase (TIM) is a model of catalytic efficiency. The 11 residue loop 6 at the TIM active site plays a major role in this enzymatic prowess. The loop moves between open and closed states, which facilitate substrate access and catalysis, respectively. The N and C-terminal hinges of loop 6 control this motion. Here, we detail flexibility requirements for hinges in a comparative solution NMR study of wild-type (WT) TIM and a quintuple mutant (PGG/GGG). The latter contained glycine substitutions in the N-terminal hinge at Val167 and Trp168, which follow the essential Pro166, and in the C-terminal hinge at Lys174, Thr175, and Ala176. Previous work demonstrated that PGG/GGG has a tenfold higher Km value and 10(3)-fold reduced k(cat) relative to WT with either d-glyceraldehyde 3-phosphate or dihyrdroxyacetone phosphate as substrate. Our NMR results explain this in terms of altered loop-6 dynamics in PGG/GGG. In the mutant, loop 6 exhibits conformational heterogeneity with corresponding motional rates <750 s(-1) that are an order of magnitude slower than the natural WT loop 6 motion. At the same time, nanosecond timescale motions of loop 6 are greatly enhanced in the mutant relative to WT. These differences from WT behavior occur in both apo PGG/GGG and in the form bound to the reaction-intermediate analog, 2 phosphoglycolate (2-PGA). In addition, as indicated by 1H, 15N and 13CO chemical shifts, the glycine substitutions diminished the enzyme's response to ligand, and induced structural perturbations in apo and 2-PGA-bound forms of TIM that are atypical of WT. These data show that PGG/GGG exists in multiple conformations that are not fully competent for ligand binding or catalysis. These experiments elucidate an important principle of catalytic hinge design in proteins: structural rigidity is essential for focused motional freedom of active-site loops. PMID- 17336329 TI - Differentiation of women with premenstrual dysphoric disorder, recurrent brief depression, and healthy controls by daily mood rating dynamics. AB - Enhanced statistical characterization of mood-rating data holds the potential to more precisely classify and sub-classify recurrent mood disorders like premenstrual dysphoric disorder (PMDD) and recurrent brief depressive disorder (RBD). We applied several complementary statistical methods to differentiate mood rating dynamics among women with PMDD, RBD, and normal controls (NC). We compared three subgroups of women: NC (n=8); PMDD (n=15); and RBD (n=9) on the basis of daily self-ratings of sadness, study lengths between 50 and 120 days. We analyzed mean levels; overall variability, SD; sequential irregularity, approximate entropy (ApEn); and a quantification of the extent of brief and staccato dynamics, denoted 'Spikiness'. For each of SD, irregularity (ApEn), and Spikiness, we showed highly significant subgroup differences, ANOVA0.001 for each statistic; additionally, many paired subgroup comparisons showed highly significant differences. In contrast, mean levels were indistinct among the subgroups. For SD, normal controls had much smaller levels than the other subgroups, with RBD intermediate. ApEn showed PMDD to be significantly more regular than the other subgroups. Spikiness showed NC and RBD data sets to be much more staccato than their PMDD counterparts, and appears to suitably characterize the defining feature of RBD dynamics. Compound criteria based on these statistical measures discriminated diagnostic subgroups with high sensitivity and specificity. Taken together, the statistical suite provides well defined specifications of each subgroup. This can facilitate accurate diagnosis, and augment the prediction and evaluation of response to treatment. The statistical methodologies have broad and direct applicability to behavioral studies for many psychiatric disorders, and indeed to similar analyses of associated biological signals across multiple axes. PMID- 17336330 TI - Hemodynamic responses elicited by gamma2-MSH or blood replacement in hemorrhaged rats. AB - BACKGROUND: Systemic injections of compounds such as gamma(2)-melanocyte stimulating hormone (gamma(2)-MSH), which increase sympathetic neurogenic vasoconstriction, may be beneficial in treating hemorrhage-induced hypotension. METHODS: This study characterized (1) the hemodynamic responses elicited by systemic injections of gamma(2)-MSH in pentobarbital-anesthetized hemorrhaged rats, and (2) the hemodynamic responses elicited by the replacement of withdrawn blood in these rats. RESULTS: Controlled hemorrhage (4.8 +/- 0.3 mL/rat at 1.5 mL/min) resulted in a pronounced and sustained fall in mean arterial blood pressure (MAP). The fall in MAP was associated with a reduction in heart rate (HR) and hindquarter (HQR) vascular resistance but no changes in mesenteric (MR) or renal (RR) vascular resistances. Systemic injections of gamma(2)-MSH (10-40 microg/kg, i.v.) produced dose-dependent increases in HR, MAP, and vascular resistances of 20 to 60 s in duration in the hemorrhaged rats. In contrast, injection of the withdrawn blood produced an immediate and sustained increase in MAP, which was associated with a pronounced vasodilation in the hindquarter bed but no changes in MR or RR. CONCLUSIONS: These findings suggest that although gamma(2)-MSH elicits pressor and vasoconstrictor responses in hemorrhaged rats, the bolus injection of this peptide may not in itself be an effective strategy for the sustained restoration of MAP in these rats. Moreover, although blood replacement effectively restores MAP via increases in cardiac output rather than total peripheral resistance, it appears that this manipulation produces an active vasodilation in the hindquarter bed. The possibility that this vasodilation involves a sympathetic neurogenic vasodilator system, which innervates the hindlimb vascular bed but not mesenteric or renal vascular beds, will be discussed. PMID- 17336331 TI - Heat stress attenuates ATP-depletion and pH-decrease during cardioplegic arrest. AB - BACKGROUND: The capacity of heat stress induction to improve myocardial tolerance against ischemia is well known. We investigated cardiac energy metabolism after hsp 72(+)/73(+) induction in isolated perfused neonatal rabbit hearts subjected to prolonged cold cardioplegic ischemia. METHODS: Hearts from neonatal rabbits were excised, isolated perfused and arrested by 2-h cold cardioplegic ischemia. Rectal temperature of eight neonatal rabbits was raised to 42.0 to 42.5 degrees C for heat shock protein expression in a whole body water bath for 15 min before the onset of arrest. Another set of eight rabbits without hyperthermia pretreatment served as control. Recovery of left ventricle function was assessed by aortic flow, cardiac output, and max dP/dt. Status of high-energy phosphates was measured by (31)phosphorus nuclear magnetic resonance-spectroscopy. RESULTS: Immunoblot analysis revealed clear hsp 72+/73+ induction after a brief period of systemic hyperthermia. Heat stress pretreatment resulted in a better recovery of left ventricular function (aortic flow and cardiac output improvement P < 0.05, max dP/dt P < 0.01) than in controls at 60 min after reperfusion. During ischemia and reperfusion, myocardial energy metabolism was better preserved in hearts after hsp induction as a consequence of increased gamma-, alpha-, and beta-ATP as well as phosphocreatine-values over controls. The ischemia-induced pH-decrease was attenuated. CONCLUSION: These data contribute to the evidence of heat stress mediated beneficial effects on functional myocardial recovery and improved cardiac energy metabolism after prolonged cold cardioplegic ischemia. More importantly, the attenuation of ischemic pH reduction and better restoration suggest an involvement of mitochondrial membrane potential alterations. PMID- 17336332 TI - Development of a mouse model for evaluation of small diameter vascular grafts. AB - BACKGROUND: It is estimated that 80,000 individuals are unable to undergo life or limb saving bypass surgery because of inadequate small caliber synthetic vascular grafts. The use of tissue engineering methods has been proposed as a potential means of creating improved vascular conduits. We have developed a severe combined immunodeficiency (SCID) mouse aortic interposition model for initial evaluation and screening of small diameter vascular conduits in vivo. METHODS: Fifteen small diameter vascular conduits, approximately 1 mm in diameter and 10 mm in length, were implanted as infrarenal aortic interposition grafts for 1 to 35 days. Eight grafts were constructed using a decellularized ovine arterial tissue as a scaffold. Seven grafts were constructed from silastic tubing. Four grafts were composed of Polyurethane, and two were made of expanded polytetrafluroethylene. To explore noninvasive means of evaluating patency, grafts were selectively imaged using ultrasound and micro-computed tomography. RESULTS: All grafts were patent immediately post-operatively and at time of sacrifice. All imaging modalities were able to visualize the grafts and confirm patency. All specimens were sent for histology to evaluate neotissue formation and to correlate radiographic morphology with histological morphology. CONCLUSIONS: The use of the SCID mouse model for initial evaluation of small caliber grafts is feasible and provides a cost effective rapid screening model with the added advantage of being able to use human cells in further studies. PMID- 17336333 TI - The protective effects of 17beta-estradiol on hepatic ischemia-reperfusion injury in rat model, associated with regulation of heat-shock protein expression. AB - BACKGROUND: Ischemia-reperfusion (I/R) injury, which was commonly seen in the field of hepatic surgical intervention, impaired liver regeneration and predisposed to liver failure. Previous studies have shown gender dimorphic response of the liver for various hepatic stresses including I/R injury, hemorrhagic shock-resuscitation, liver cirrhosis, endotoxemia, and chronic alcoholic consumption, and demonstrated gender dimorphism in hepatocellular dysfunction after experimental trauma and hemorrhage. The objective of this study was to examine the hypothesis that the protective effects of 17beta-estradiol (E2) in hepatic I/R injury were associated with increasing heat-shock protein 70 expression. MATERIALS AND METHODS: Sprague-Dawley male and female rats were randomly divided into male and female sham, I/R, and E2 + I/R groups. The model of reduced-size liver ischemia and reperfusion was used. Except for the sham operated groups, all rats were subjected to 70% liver ischemia for 45 min followed by resection of the remaining 30% nonischemic lobes and reperfusion of ischemic tissue. For each group, five rats were used to investigate the survival during a week after operation; blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase, aspartate aminotransferase, liver tissue NO(2)(-) + NO(3)(-), malondialdehyde content, superoxide dismutase, nitric oxide synthase, and myeloperoxidase activity, Hsp70 expression, and apoptosis ratio. RESULTS: Compared with I/R groups, male and female E2 + I/R groups showed less I/R-induced injury, and SOD and eNOS activity and Hsp70 expression were increased significantly (P < 0.01). A higher rate of apoptosis was observed in the I/R group versus the E2 + I/R group, a significant increase of MDA, NO(2)(-) + NO(3)( ), and MPO of liver tissues and serum transaminase were also observed in the I/R group versus the E2 + I/R group. The survival rate was significantly higher in the male E2 + I/R group than in the male I/R group. CONCLUSION: E2 pretreatment had protective effects on liver in hepatic I/R injury. The mechanism of this protection might be related to overexpression of Hsp70. PMID- 17336334 TI - Significance of monitoring Bio-Intact PTH (1-84) during parathyroidectomy for secondary hyperparathyroidism. AB - BACKGROUND: The Bio-Intact PTH (1-84) assay has recently been developed to specifically measure the intact PTH (1-84) molecule, and in this study we used it to investigate sequential changes in serum Bio-Intact PTH (1-84) levels during parathyroidectomy for secondary HPT. MATERIAL AND METHODS: The subjects of this study were 70 patients (41 women, 29 men) who underwent parathyroidectomy between April 2002 and March 2005. Ethylene diamine tetraacetic acid serum samples were drawn via a peripheral venous catheter after induction of anesthesia (basal), and at 5, 10, and 30 min after diseased glands excision. Serum active PTH (1-84) was measured by the Bio-Intact PTH (1-84) assay, which is a two-site chemiluminometric assay. RESULTS: When 4 or more diseased parathyroid glands were removed, the basal of Bio-Intact PTH (1-84) level in patients without persistent HPT (52 cases) was 539 +/- 355 pg/mL. The level of the Bio-Intact PTH (1-84) at 30 min after sufficient parathyroidectomy had decreased to less than 45 pg/mL, whereas the Bio-Intact PTH (1-84) level in patients with persistent HPT at 30 min was greater than 45 pg/mL (3 cases). After removal of three or fewer diseased parathyroid glands (15 cases), the Bio-Intact PTH (1-84) at 30 min in patients without persistent HPT (13 cases) was less than 45 pg/mL. The 2 patients whose the Bio-Intact PTH (1-84) at 30 min was greater than 45 pg/mL underwent reoperation, and residual enlarged parathyroid gland in the neck was removed. CONCLUSIONS: The Bio-Intact PTH (1-84) level at 30 min after parathyroidectomy seems to be useful for judging whether the parathyroidectomy is complete irrespective of the number of glands removed from patients with secondary HPT. When only three diseased parathyroid glands are removed, the surgeon can decide whether to continue or stop neck exploration according to the level of Bio-Intact PTH (1-84) at 30 min. PMID- 17336335 TI - The effect of antagonism of adenosine A1 receptor against ischemia and reperfusion injury of the liver. AB - BACKGROUND: Adenosine is known to exert protective roles in hepatic ischemia and reperfusion injury, while all adenosine receptors do not play the cytoprotective roles. We have tested our hypothesis that blockage of adenosine binding to A(1) receptor by its antagonist, KW3902 [8-(noradamantan-3-yl)-1,3-dipropylxanthine] attenuates hepatic ischemia-reperfusion injury. METHODS: Adult female beagle dogs underwent a 2 h total hepatic vascular exclusion (THVE) with a venovenous bypass. Nontreated animals that underwent THVE with a venovenous bypass alone were used as the control (Group CT, n=6). KW3902 was given to the animals by continuous intraportal infusion for 60 min before ischemia at a dose of 1 microg/kg/min (Group KW, n=6). Two wk survival, hemodynamics, hepatic tissue blood flow (HTBF), liver function, energy metabolism, cAMP concentration, and histopathological findings were studied. RESULTS: Two wk animal survival was significantly improved in group KW compared with that in group CT (group CT: 16.7% versus group KW: 83.3%). HTBF, liver function, and hepatic adenine nucleotide concentration were remarkably better in group KW than group CT. In addition, cAMP concentration in group KW was maintained significantly higher than group CT. Histopathological examination revealed preservation of hepatic architecture and suppression of neutrophil infiltration into hepatic tissue in group KW. CONCLUSION: Administration of adenosine A(1) receptor antagonist before ischemia attenuates hepatic ischemia-reperfusion injury. To elicit the beneficial effect of adenosine against ischemia and reperfusion injury of the liver, it is important to oppose adenosine A1 receptor activation. PMID- 17336336 TI - Cerebral blood supply with aging: normal, stenotic and recanalized. AB - The prosperity of brain parenchyma during aging depends on the preservation of cerebral blood flow (CBF) parameters. We have analysed ultrasonographic measurements of peak systolic (PSV) and end diastolic velocities (EDV) along with pulsatility (PI) and resistance indexes (RI) in common (CCA), internal (ICA) and external carotid artery (ECA) (N=199) and in vertebral arteries (VA) (N=200) in patients without any signs of stenosis. In two other cohorts patients with internal carotid artery stenosis (N=231) and patients prior to and after therapeutic recanalization (N=81) were evaluated in the same parameters. RESULTS: in the range of 21-92 years PSV in CCA decreases by 7 mm/s/year, while in ICA only by 2.31 mm/s/year. The decrease of EDV in carotid arteries occurs between 1.72 and 2.28 mm/s/year. PSV in VA drops down by 0.91 mm/s/year, EDV by 0.86 mm/s/year. PI and RI increase with age in all vessels, but not significantly. Stenotic ICAs are associated with increased PSV in the range of 0.7-2.9 m/s, but also with an increasing PSV variability along the growing stenosis in individual patients. In all degrees of stenoses some patients preserve normal velocities. In average the increment for each 10% of the stenosis below 50% makes 8 cm/s, while above 50% it makes already 50 cm/s. In persons with bilateral stenoses the increment with growing stenosis is steeper. The restoration of normal ICA lumen by means of carotid endarterectomy or by angioplasty with stenting results in an average drop by 1.23 m/s in PSV and by 0.4 m/s in EDV. We have investigated the ophthalmic artery and other substitution supplies and deduce, that the remarkable differences in blood flow velocity reactions to a compromised carotid lumen depend on the formation of collaterals in mutual interplay with peripheral resistance. PMID- 17336337 TI - Homocysteine and Parkinson's disease: a dangerous liaison? AB - Homocysteine, a sulphur-containing amino acid formed by demethylation of methionine, is involved in numerous processes of methyl group transfer, all playing pivotal roles in the biochemistry of the human body. Increased levels of plasma homocysteine (hyperhomocysteinemia) - which may result from a deficiency of folate, vitamin B6 or B12 or mutations in enzymes regulating the catabolism of homocysteine - are associated with a wide range of clinical manifestations, mostly affecting the central nervous system (e.g., mental retardation, cerebral atrophy and epileptic seizures). Recent evidence suggests that changes in the metabolic fate of homocysteine, leading to hyperhomocysteinemia, may also play a role in the pathophysiology of neurodegenerative disorders, particularly Parkinson's disease (PD). The nervous system might be particularly sensitive to homocysteine, due to the excitotoxic-like properties of the amino acid. However, experimental findings have shown that homocysteine does not seem to posses direct, cytotoxic activity, while the amino acid has proven able to synergize with more specific neurotoxic insults. Hyperhomocysteinemia has been repeatedly reported in PD patients; the increase, however, seems mostly related to the methylated catabolism of l-Dopa, the main pharmacological treatment of PD. Therefore, hyperhomocysteinemia may not be specific to movement disorders or other neurological diseases, the condition being, in fact, rather the result of the combinations of different factors, mainly metabolic, but also genetic and pharmacological, intervening in the neurodegenerative process. PMID- 17336338 TI - A standardized root extract of Withania somnifera and its major constituent withanolide-A elicit humoral and cell-mediated immune responses by up regulation of Th1-dominant polarization in BALB/c mice. AB - The effects of graded doses of a chemically standardized aqueous alcoholic (1:1) root extract (AGB) of Withania somnifera on the immune system of SRBC immunized BALB/c mice were investigated. Mice were administrated AGB orally for 15 days. AGB stimulated cell mediated immunity, IgM and IgG titers reaching peak value with 30 mg/kg b.wt. Flow cytometric analysis of lymphocyte surface markers of T cells (CD3(+), CD4(+) and CD8(+)) and B cells (CD19(+)) indicated prominent enhancement in proliferation and differentiation of lymphocytes. The extract selectively, induced type 1 immunity because it guided enhanced expression of T helper cells (Th)1 cytokines interferon (IFN)-gamma and interleukin (IL)-2 while Th2 cytokine IL-4 observed a moderate decline. Confirmation of Th1 polarization was obtained from augmented levels of IgG2a over IgG1 in the blood sera of AGB treated groups. Withanolide-A, a major constituent of AGB appeared responsible for Th1 skewing effect of the extract as it significantly increased the levels of Th1 cytokines, decreased moderately IL-4 and significantly restored the selective dexamethasone inhibition of Th1 cytokines in mouse splenocytes cultures in vitro. In addition, AGB also strongly activated macrophage functions ex vivo and in vitro indicated by enhanced secretion of nitrite, IL-12 and TNF-alpha. In contrast IL-10 remained unchanged again suggesting that AGB critically influenced Th1 profile of the cytokines. The studies suggested that AGB supports predominantly Th1 immunity with increase in macrophage functions. The standardized root extract of no toxicological consequences might therefore, find useful applications against the intracellular pathogens and in the management of immune suppressed diseases. PMID- 17336339 TI - Estimating incidence of the French BSE infection using a joint analysis of both asymptomatic and clinical BSE surveillance data. AB - Bovine Spongiform Encephalopathy (BSE) clinical surveillance data were the main source of information to perform back-calculation of BSE infection incidence. Since 2001, systematic BSE screening tests enhanced the clinical surveillance and allowed to detect some preclinical, i.e. asymptomatic, cases of BSE. We propose a method to incorporate additional information provided by screening tests. It was the first time that a back-calculation model was developed for a full BSE clinical surveillance. In the spirit, our approach resembles what it was done in the Acquired Immune Deficiency Syndrome (AIDS) epidemic to incorporate the Human Immunodeficiency Virus (HIV) diagnosis. Nevertheless, in the BSE epidemic, we had to consider different surveillance systems, their peculiarity, and the phenomenon of communicating vessels between these surveillance systems. In addition, both the preclinical sensitivity of tests and the status of BSE cases, asymptomatic or clinical, were not precisely known. We applied the model to the French BSE epidemic in order to obtain an updated estimate of the incidence of BSE infection. Our back-calculation model fitted very well the observed data of each surveillance system. We detected a lengthening of the incubation period and estimated that the number of infections was very small in the late 1990s and zero in July 2001. PMID- 17336340 TI - Hypoxia inducible factor-1 modulates hemin-induced IL-8 secretion in microvascular endothelium. AB - Ischemia/Reperfusion injury and hemolysis are characterized by erythrocyte lysis and release of free heme into the microcirculation. Following substantial erythrocyte lysis, heme overwhelms circulatory heme-binding protein networks rapidly forming hemin, the oxidized form of iron protoporphyrin IX. Hemin's role in modulating inflammatory responses in microvascular endothelium (MVEC) remains ill-defined. We studied the impact of hemin exposure on human MVEC interleukin-8 (IL-8) expression. Hemin significantly up-regulated MVEC IL-8 secretion and was associated with cellular iron loading. Hemin-induced IL-8 up-regulation was significantly attenuated by increasing environmental serum concentrations. As well, hemin-induced IL-8 secretion was significantly reduced in a concentration dependent fashion following pyrrolidine dithiocarbamate exposure, suggesting that induction occurred via an oxidant-sensitive mechanism. Interestingly, transfection studies revealed that oxidant-driven transcription factors NF-kappaB and AP-1 played no role in hemin-induced IL-8 transcription. In studies employing actinomycin D, hemin was found to dramatically lengthen IL-8 mRNA half-life. Of major importance in the current report was the finding that hypoxia inducible factor-1 (HIF-1), a powerful transcription factor mediating tissue responses to hypoxia, potently regulated hemin-induced IL-8 secretion in human MVEC. Activation of HIF-1 via the prolyl hydroxylase inhibitor dimethyloxalylglycine attenuated hemin-induced IL-8 secretion. These studies were confirmed via DNA directed siRNA silencing of HIF-1alpha. In conclusion, hemin induces a serum protein-sensitive pro-inflammatory phenotype in MVEC via an oxidant-sensitive mechanism that is powerfully regulated by HIF-1. PMID- 17336341 TI - [Endovascular treatment of idiopathic intracranial hypertension. Analysis of eight consecutive patients]. AB - INTRODUCTION: Optic nerve sheath fenestration or ventricular shunting are classically proposed after failure of medical treatment. Idiopathic intracranial hypertension is caused by venous sinus obstruction in an unknown percentage of cases. Recently, endoluminal venous sinus stenting was proposed as an alternative treatment. PATIENTS AND METHOD: Between September 2003 and December 2004, eight consecutive patients with a diagnosis of idiopathic intracranial hypertension underwent MRI venography and direct retrograde cerebral angiography. RESULTS: There were five females and three males aged 22 to 55 years. All patients had vision disorders. The cerebrospinal fluid pressure ranged from 27 to 45 mmHg with normal composition. All patients presented at least one sinus stenosis. Endovascular stenting of the stenotic venous sinus was performed under intravenous heparin administration. Anti-platelet therapy was administered for 3 months post treatment. Intra-sinus pressures were invariably reduced by stenting. Mean follow-up was 18 months. All patients improved clinically. The cerebrospinal fluid pressure had normalized at 3-month follow-up in all patients. In all patients, multidetector row CT-angiography or MRI venography was performed at 3-, 6- and 12-month follow-up and demonstrated the patency of the stent. DISCUSSION: The importance of venous sinus disease as a cause of idiopathic intracranial hypertension is probably underestimated. Patients with idiopathic intracranial hypertension should be evaluated with direct retrograde cerebral venography and manometry. In patients with venous sinus lesions, treatment by an endoluminal venous sinus stent is a safe and effective alternative for amenable lesions. PMID- 17336342 TI - Upregulation of nitric oxide synthase II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following induction of experimental temporal lobe status epilepticus in the rat. AB - Status epilepticus results in preferential neuronal cell loss in the hippocampus. We evaluated the hypothesis that the repertoire of intracellular events in the vulnerable hippocampal CA3 subfield after induction of experimental temporal lobe status epilepticus entails upregulation of nitric oxide synthase II (NOS II), followed by the release of mitochondrial cytochrome c that triggers the cytosolic caspase-3 cascade, leading to apoptotic cell death. In Sprague-Dawley rats, significant and temporally correlated upregulation of NOS II (3-24h), but not NOS I or II expression, enhanced cytosolic translocation of cytochrome c (days 1 and 3), augmented activated caspase-3 in cytosol (days 1, 3 and 7) and DNA fragmentation (days 1, 3 and 7) was detected bilaterally in the hippocampal CA3 subfield after elicitation of sustained seizure activity by microinjection of kainic acid into the unilateral CA3 subfield. Application bilaterally into the hippocampal CA3 subfield of a selective NOS II inhibitor, S-methylisothiourea, significantly blunted these apoptotic events; a selective NOS I inhibitor, N(omega)-propyl-l-arginine or a potent NOS III inhibitor, N(5)-(1-iminoethyl)-l ornithine was ineffective. We conclude that upregulation of NOS II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following the induction of experimental temporal lobe status epilepticus. PMID- 17336344 TI - Amygdala function in adolescents with congenital adrenal hyperplasia: a model for the study of early steroid abnormalities. AB - Early disruption of steroids affects the development of mammalian neural circuits underlying affective processes. In humans, patients with classic congenital adrenal hyperplasia (CAH) can serve as a natural model to study early hormonal alterations on functional brain development. CAH is characterized by congenital glucocorticoid insufficiency, leading to altered hypothalamic-pituitary-adrenal (HPA) function, and hyperandrogenism. Using fMRI, we compared fourteen adolescents with CAH to 14 healthy controls on amygdala response to a face viewing task. In response to negative facial emotions, CAH females activated the amygdala significantly more than healthy females, whereas CAH males did not differ from control males. Furthermore, females with CAH showed a similar pattern of amygdala activation to control males, suggesting virilized amygdala function in females with CAH. These findings suggest a prominent effect of early hyperandrogenism on the development and function of the amygdala in females with CAH, whereas no effects were detected in males with CAH. This study provides data that can be further tested in a model of the neurobiological mechanisms underlying early androgen organizational effects on amygdala function. PMID- 17336343 TI - CC12, a high-affinity ligand for [3H]cimetidine binding, is an improgan antagonist. AB - Improgan, a chemical congener of cimetidine, is a highly effective non-opioid analgesic when injected into the CNS. Despite extensive characterization, neither the improgan receptor, nor a pharmacological antagonist of improgan has been previously described. Presently, the specific binding of [(3)H]cimetidine (3HCIM) in brain fractions was used to discover 4(5)-((4-iodobenzyl)thiomethyl)-1H imidazole, which behaved in vivo as the first improgan antagonist. The synthesis and pharmacological properties of this drug (named CC12) are described herein. In rats, CC12 (50-500nmol, i.c.v.) produced dose-dependent inhibition of improgan (200-400nmol) antinociception on the tail flick and hot plate tests. When given alone to rats, CC12 had no effects on nociceptive latencies, or on other observable behavioral or motor functions. Maximal inhibitory effects of CC12 (500nmol) were fully surmounted with a large i.c.v. dose of improgan (800nmol), demonstrating competitive antagonism. In mice, CC12 (200-400nmol, i.c.v.) behaved as a partial agonist, producing incomplete improgan antagonism, but also limited antinociception when given alone. Radioligand binding, receptor autoradiography, and electrophysiology experiments showed that CC12's antagonist properties are not explained by activity at 25 sites relevant to analgesia, including known receptors for cannabinoids, opioids or histamine. The use of CC12 as an improgan antagonist will facilitate the characterization of improgan analgesia. Furthermore, because CC12 was also found presently to inhibit opioid and cannabinoid antinociception, it is suggested that this drug modifies a biochemical mechanism shared by several classes of analgesics. Elucidation of this mechanism will enhance understanding of the biochemistry of pain relief. PMID- 17336345 TI - ERP correlates of the bilateral redundancy gain for words. AB - Neurophysiological correlates of hemispheric asymmetry and interhemispheric interaction in lexical processing were investigated in a lexical decision task with tachistoscopic stimulus presentation either unilaterally, to the right or left visual field, or bilaterally, with identical stimulus copies to each visual hemi-field. Behavioral data confirmed both right visual field advantage and bilateral redundancy gain for words but not for pronounceable orthographically regular pseudowords. ERPs showed a significant amplitude increase 160-200 after stimulus presentation specifically for words after bilateral redundant stimulation, which was present in the recordings from both hemispheres. Localization of cortical sources using minimum norm estimation indicated stronger cortical activity for words in temporal regions of both hemispheres after bilateral presentation compared with each of the unilateral stimulation conditions individually. Pseudoword presentation did not lead to a general increase of cortical activation in the bilateral condition compared with unilateral presentation. The specific activation increase for words in the bilateral redundant condition relative to unilateral stimulation and the absence of this effect for pseudowords, which became manifest in a significant interaction of the factors lexicality and presentation mode, is best explained by summation of neuronal activation from both hemispheres within distributed lexical circuits. Source estimation indicates that temporal areas, particularly in the left hemisphere, are the primary cortical loci where such stimulus-specific activity increases occurred. PMID- 17336347 TI - A comment on a neuroimaging study of natural language quantifier comprehension. PMID- 17336346 TI - Atypical [corrected] participation of visual cortex during word processing in autism: an fMRI study of semantic decision. AB - Language delay and impairment are salient features of autism. More specifically, there is evidence of atypical semantic organization in autism, but the functional brain correlates are not well understood. The current study used functional MRI to examine activation associated with semantic category decision. Ten high functioning men with autism spectrum disorder and 10 healthy control subjects matched for gender, handedness, age, and nonverbal IQ were studied. Participants indicated via button press response whether visually presented words belonged to a target category (tools, colors, feelings). The control condition required target letter detection in unpronounceable letter strings. Significant activation for semantic decision in the left inferior frontal gyrus (Brodmann areas 44 and 45) was found in the control group. Corresponding activation in the autism group was more limited, with smaller clusters in left inferior frontal areas 45 and 47. Autistic participants, however, showed significantly greater activation compared to controls in extrastriate visual cortex bilaterally (areas 18 and 19), which correlated with greater number of errors on the semantic task. Our findings suggest an important role of perceptual components (possibly visual imagery) during semantic decision, consistent with previous evidence of atypical lexicosemantic performance in autism. In the context of similar findings from younger typically developing children, our results suggest an immature pattern associated with inefficient processing, presumably due to atypical experiential embedding of word acquisition in autism. PMID- 17336348 TI - Dietary protein level alters gentamicin-induced nephrotoxicity in rats. AB - Aminoglycosides (AG) such as gentamicin are antimicrobial drugs widely used in the hospital setting due to their efficacy in the treatment of severe gram negative bacterial infections. However, all AG have the potential to cause nephrotoxicity. Two studies have been conducted (1) to assess the protein level of a diet that would give the best renal outcome with gentamicin administration, and (2) to get a better idea about the rhythms of food ingestion associated with the different protein levels. Adult female Sprague-Dawley rats fully adapted to a standard chow diet, the standard chow with 20% or 55% added casein were chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution. Food ingestion patterns of rats were recorded every hour using a Diet Scan system and gentamicin nephrotoxicity indices were measured. The second study used rats that were fed the same diets and given a sham injection. Corticosterone was assayed to quantify the stress of the animals. Results showed that chronic gentamicin treatment leads to a decrease in food intake and flattening of the rhythms of food ingestion. Also, chow feeding and the 20% casein diet were found to be more protective against gentamicin-induced nephrotoxicity than the 55% casein diet. Therefore, while a protein-rich diet can be protective against gentamicin-induced nephrotoxicity, the present study demonstrates that a diet too high in protein might rather be harmful to the kidneys. PMID- 17336349 TI - Bioactive natural products from marine cyanobacteria for drug discovery. AB - The prokaryotic marine cyanobacteria continue to be an important source of structurally bioactive secondary metabolites. A majority of these molecules are nitrogen-containing compounds biosynthesized by large multimodular nonribosomal polypeptide (NRP) or mixed polyketide-NRP enzymatic systems. A total of 128 marine cyanobacterial alkaloids, published in the literature between January 2001 and December 2006, are presented in this review with emphasis on their biosynthesis and biological activities. In addition, a number of highly cytotoxic compounds such as hectochlorin, lyngbyabellins, apratoxins, and aurilides have been identified as potential lead compounds for the development of anticancer agents. A brief coverage on the distribution of natural product biosynthetic genes as well as the mechanisms of tailoring enzymes involved in the biosynthesis of cyanobacterial compounds will also be given. PMID- 17336350 TI - Xylogalacturonan exists in cell walls from various tissues of Arabidopsis thaliana. AB - Evidence is presented for the presence of xylogalacturonan (XGA) in Arabidopsis thaliana. This evidence was obtained by extraction of pectin from the seeds, root, stem, young leaves and mature leaves of A. thaliana, followed by treatment of these pectin extracts with xylogalacturonan hydrolase (XGH). Upon enzymatic treatment, XGA oligosaccharides were primarily produced from pectin extracts obtained from the young and mature leaves and to a lesser extent from those originating from the stem of A. thaliana. The oligosaccharide GalA(3)Xyl was predominantly formed from these pectin extracts. No XGA oligosaccharides were detected in digests of pectin extracts from the seeds and roots. A low number of XGA oligosaccharides was obtained from pectins of A. thaliana. This indicates a uniform distribution of xylose in XGA from A. thaliana. The predominant production of GalA(3)Xyl, as well as the release of linear GalA oligosaccharides pointed to a lower degree of xylose substitution in XGA from A. thaliana than in XGA from apple and potato. The estimated amount of XGA accounted for approximately 2.5%, 7% and 6% (w/w) of the total carbohydrate in the pectin fraction of the stem, young leaves and mature leaves, respectively. PMID- 17336351 TI - Access by elderly patients with hip fractures to public hospitals in the city of Rio de Janeiro, Brazil. PMID- 17336352 TI - Inequalities in mortality by marital status during socio-economic transition in Lithuania. AB - OBJECTIVES: To analyse the changes in mortality inequalities by marital status over the period of socio-economic transition in Lithuania and to estimate the contribution of major causes of death to marital-status differences in overall mortality. METHODS: A survey based on routine mortality statistics and census data for 1989 and 2001 for the entire country. RESULTS: The proportion of married population has declined over the past decade. Widowed men and never married women were found to be at highest risk of mortality throughout the period under investigation. Although inequalities have not grown considerably, mortality rates have increased significantly for divorced populations and for never married men, widening the mortality gap. Cardiovascular diseases contributed most to excess mortality of never married and divorced men, as well as all unmarried groups of women. The excess mortality of widowed men from external causes was greatest in 2001. CONCLUSIONS: Marriage can be considered as a health protecting factor, particularly in relation to mortality from cardiovascular diseases and external causes. Local and national policies aimed at health promotion must focus primarily on improving the position of unmarried groups and providing psychological support. PMID- 17336353 TI - Trends in disasters in Spain and their impact on public health: 1950-2005. PMID- 17336354 TI - Phenotypic and genetic characterization of Salmonella enterica subsp. enterica serovar Typhimurium isolated from pigs in Rio Grande do Sul, Brazil. AB - This study aimed to investigate the relatedness of porcine Salmonella enterica subsp. enterica (S.) serovar Typhimurium strains isolated in Southern Brazil. Sixty-six isolates from pigs belonging to three commercial companies were submitted to phage typing, XbaI-macrorestriction (PFGE), IS200 hybridization, rep PCR, antimicrobial susceptibility testing, and PCR assay targeting the spvR region. All strains presented a unique rep-PCR pattern and 63 strains had a common IS200 profile. One pulse-type (XA) was the most prevalent (39/66 strains) and included strains of phage types DT177, DT192, DT194 and RDNC. The spvR region was detected in three strains, which harboured plasmids of 90 kb. High rates of tetracycline, sulfonamide and streptomycin resistance were found. Isolates from farms located in different geographic regions but associated to the same commercial companies clustered together and presented a common resistance profile. Results suggested that clonal groups of S. Typhimurium are present in pig commercial companies in Southern Brazil. PMID- 17336355 TI - Genetic variation of the lambdaA and lambdaC protein encoding genes of avian reoviruses. AB - Sequence and phylogenetic analysis of lambdaA and lambdaC protein encoding genes of 12 avian reoviruses is described. The sequence of lambdaA possesses a variable region (residues 19-51) located within a conserved hydrophilic region (residues 1 110) and a C(2)H(2) zinc-binding motif (residues 182-202). lambdaC shows the two conserved K residues at positions 169 and 188 indicative of guanylyltransferase activity, an ATP/GTP-binding site motif A (residues 379-386), and a conserved S adenosyl-l-methionine-binding motif (residues 822-830). Pairwise sequence comparisons show that the mean sequence identities of lambdaA encoding genes and lambdaA proteins are 92% and 98%, respectively, and those of lambdaC encoding genes and lambdaC proteins are 91% and 95%, respectively. Phylogenetic analysis of lambdaA and lambdaC encoding genes reveals that both encoding genes have diverged into three distinct lineages, respectively, and that there is no correlation between lineages and viral serotypes or pathotypes. Also, reassortment of gene segments L1 and L3 has been observed between viruses. PMID- 17336356 TI - Identification of a proteinase K resistant protein for use as an internal positive control marker in PrP Western blotting. AB - The routine use of an internal positive control (IPC) marker could prove useful in the diagnosis of transmissible spongiform encephalopathy (TSE) diseases, particularly in surveillance programmes where large numbers of negative results are reported. Detection of an endogenous IPC protein in a negative sample adds confidence to the correct sample processing throughout the analytical procedure and could avoid the reporting of false negative diagnoses. Proteinase K (PK) resistance is one of the key diagnostic determinants of the disease-associated form of PrP (PrP(Sc)), the only disease-specific macromolecule currently associated with TSE disease. Additional PK resistant proteins, endogenous to TSE suspect diagnostic tissue samples, were therefore assessed for use as IPC markers in the Western blot diagnosis of BSE and scrapie. Results indicated that, whilst essentially maintaining a standard PrP extraction and detection protocol, a ferritin heavy chain sub-unit of approximately 22kDa, was consistently detected in all PK treated TSE positive and negative tissue samples tested. Its presence in a range of sample types, any of which could be submitted under BSE and scrapie surveillance programmes, confirmed it as a suitable protein for an IPC marker in PrP(Sc) Western blotting. PMID- 17336357 TI - Muscular system of a peculiar parasitic cnidarian Polypodium hydriforme: a phalloidin fluorescence study. AB - Musculature of the free-living stages of Polypodium hydriforme has been studied using phalloidin fluorescence method and confocal microscopy. P. hydriforme is a unique cnidarian possessing only smooth muscle cells situated within the mesoglea, not epithelial muscle cells, like the rest of cnidarians. Phalloidin fluorescence on whole mount preparations demonstrates an extensively developed subepidermal muscle system mostly consisting of long parallel fibers running along the tentacles. For the first time along with contracted muscle fibers we could clearly demonstrate relaxed fibers looking as long spirals. System of thin parallel circular F-actin positive fibers has been discovered outside of longitudinal muscles. The body of the animal and the mouth cone contain weakly developed parallel muscles. No special attachment of the muscle fibers to the tips of the tentacles or to the rim of the mouth has been observed. The results are discussed in connection with the "triploblastic" organization of P. hydriforme and its phylogenetic position. PMID- 17336359 TI - Workshop overview: arsenic research and risk assessment. AB - The chronic exposure of humans through consumption of high levels of inorganic arsenic (iAs)-contaminated drinking water is associated with skin lesions, peripheral vascular disease, hypertension, and cancers. Additionally, humans are exposed to organic arsenicals when used as pesticides and herbicides (e.g., monomethylarsonic acid, dimethylarsinic acid (DMA(V)) also known as cacodylic acid). Extensive research has been conducted to characterize the adverse health effects that result from exposure to iAs and its metabolites to describe the biological pathway(s) that lead to adverse health effects. To further this effort, on May 31, 2006, the United States Environmental Protection Agency (USEPA) sponsored a meeting entitled "Workshop on Arsenic Research and Risk Assessment". The invited participants from government agencies, academia, independent research organizations and consultants were asked to present their current research. The overall focus of these research efforts has been to determine the potential human health risks due to environmental exposures to arsenicals. Pursuant in these efforts is the elucidation of a mode of action for arsenicals. This paper provides a brief overview of the workshop goals, regulatory context for arsenical research, mode of action (MOA) analysis in human health risk assessment, and the application of MOA analysis for iAs and DMA(V). Subsequent papers within this issue will present the research discussed at the workshop, ensuing discussions, and conclusions of the workshop. PMID- 17336358 TI - Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: development of a mouse model for arsenic-induced diabetes. AB - Previous epidemiologic studies found increased prevalences of type 2 diabetes mellitus in populations exposed to high levels of inorganic arsenic (iAs) in drinking water. Although results of epidemiologic studies in low-exposure areas or occupational settings have been inconclusive, laboratory research has shown that exposures to iAs can produce effects that are consistent with type 2 diabetes. The current paper reviews the results of laboratory studies that examined the effects of iAs on glucose metabolism and describes new experiments in which the diabetogenic effects of iAs exposure were reproduced in a mouse model. Here, weanling male C57BL/6 mice drank deionized water with or without the addition of arsenite (25 or 50 ppm As) for 8 weeks. Intraperitoneal glucose tolerance tests revealed impaired glucose tolerance in mice exposed to 50 ppm As, but not to 25 ppm As. Exposure to 25 and 50 ppm As in drinking-water resulted in proportional increases in the concentration of iAs and its metabolites in the liver and in organs targeted by type 2 diabetes, including pancreas, skeletal muscle and adipose tissue. Dimethylarsenic was the predominant form of As in the tissues of mice in both 25 and 50 ppm groups. Notably, the average concentration of total speciated arsenic in livers from mice in the 50 ppm group was comparable to the highest concentration of total arsenic reported in the livers of Bangladeshi residents who had consumed water with an order of magnitude lower level of iAs. These data suggest that mice are less susceptible than humans to the diabetogenic effects of chronic exposure to iAs due to a more efficient clearance of iAs or its metabolites from target tissues. PMID- 17336360 TI - A new DNA binding protein highly conserved in diverse crenarchaeal viruses. AB - Sulfolobus turreted icosahedral virus (STIV) infects Sulfolobus species found in the hot springs of Yellowstone National Park. Its 37 open reading frames (ORFs) generally lack sequence similarity to other genes. One exception, however, is ORF B116. While its function is unknown, orthologs are found in three additional crenarchaeal viral families. Due to the central importance of this protein family to crenarchaeal viruses, we have undertaken structural and biochemical studies of B116. The structure reveals a previously unobserved fold consisting of a five stranded beta-sheet flanked on one side by three alpha helices. Two subunits come together to form a homodimer with a 10-stranded mixed beta-sheet, where the topology of the central strands resembles an unclosed beta-barrel. Highly conserved loops rise above the surface of the saddle-shaped protein and suggest an interaction with the major groove of DNA. The predicted B116-DNA interaction is confirmed by electrophoretic mobility shift assays. PMID- 17336361 TI - Preventing HIV-1 Tat-induced neuronal apoptosis using antioxidant enzymes: mechanistic and therapeutic implications. AB - HIV-1 proteins, especially gp120 and Tat, elicit reactive oxygen species (ROS) and cause neuron apoptosis. We used antioxidant enzymes, Cu/Zn superoxide dismutase (SOD1) and glutathione peroxidase (GPx1) to study signaling and neuroprotection from Tat-induced apoptosis. SOD1 converts superoxide to peroxide; GPx1 converts peroxide to water. Primary human neurons were transduced with SV40 derived vectors carrying SOD1 and GPx1, then HIV-1 Tat protein was added. Both SV(SOD1) and SV(GPx1) delivered substantial transgene expression. Tat decreased endogenous cellular, but not transduced, SOD1 and GPx1. Tat rapidly increased neuron [Ca(2+)](i), which effect was not altered by SV(SOD1) or SV(GPx1). However, both vectors together blocked Tat-induced [Ca(2+)](i) fluxes. Similarly, neither SV(SOD1) nor SV(GPx1) protected neurons from Tat-induced apoptosis, but both vectors together did. Tat therefore activates multiple signaling pathways, in one of which superoxide acts as an intermediate while the other utilizes peroxide. Gene delivery to protect neurons from Tat must therefore target both. PMID- 17336363 TI - Molecular determinants of HIV-1 intersubtype recombination potential. AB - Sequence differences in the dimerization initiation signal (DIS) affect the rate of recombination between subtype B and subtype C HIV-1. To test the hypothesis that DIS sequences can be used to predict intersubtype recombination potentials, we measured the recombination rate between CRF01_A/E (AE) and B, which contain mismatches in the DIS, and between AE and C, which have an identical DIS. Compared with the intrasubtype recombination rate, the recombination rate between AE and subtype B virus was 9-fold lower, and the rate between AE and subtype C virus was 2-fold lower. Thus, DIS sequences can be used to predict the recombination potential between HIV-1 subtypes. Further analyses revealed that the 2-fold lower recombination rate between AE and C viruses can be restored to the intrasubtype recombination rate by matching a part of the LTR and a portion of the viral genome. Therefore, the lower intersubtype recombination rate between AE and C is not caused by a given region but is a cumulative effect by more than one region. PMID- 17336362 TI - Mapping and phenotypic analysis of spontaneous isatin-beta-thiosemicarbazone resistant mutants of vaccinia virus. AB - Treatment of wild type vaccinia virus infected cells with the anti-poxviral drug isatin-beta-thiosemicarbazone (IBT) induces the viral postreplicative transcription apparatus to synthesize longer-than-normal mRNAs through an unknown mechanism. Previous studies have shown that virus mutants resistant to or dependent on IBT affect genes involved in control of viral postreplicative transcription elongation. This study was initiated in order to identify additional viral genes involved in control of vaccinia postreplicative transcription elongation. Eight independent, spontaneous IBT resistant mutants of vaccinia virus were isolated. Marker rescue experiments mapped two mutants to gene G2R, which encodes a previously characterized postreplicative gene positive transcription elongation factor. Three mutants mapped to the largest subunit of the viral RNA polymerase, rpo147, the product of gene J6R. One mutant contained missense mutations in both G2R and A24R (rpo132, the second largest subunit of the RNA polymerase). Two mutants could not be mapped, however sequence analysis demonstrated that neither of these mutants contained mutations in previously identified IBT resistance or dependence genes. Phenotypic and biochemical analysis of the mutants suggests that they possess defects in transcription elongation that compensate for the elongation enhancing effects of IBT. The results implicate the largest subunit of the RNA polymerase (rpo147) in the control of elongation, and suggest that there exist additional gene products which mediate intermediate and late transcription elongation in vaccinia virus. PMID- 17336364 TI - Effect of hydraulic retention time on sulfate reduction in a carbon monoxide fed thermophilic gas lift reactor. AB - Thermophilic hydrogenogenic carbon monoxide (CO) converting microorganisms present in anaerobic sludge play a crucial role in the application of CO as electron donor for sulfate reduction. Hydrogenogenic CO conversion was investigated in a gas lift reactor (55 degrees C) at different hydraulic retention times (HRT). Operation at a HRT>9h resulted in predominant consumption of CO-derived H2 by methanogens (up to 90%) and thus in a poor sulfate reduction efficiency of less than 15%. At HRTs<4 h, consumption of the CO-derived H2 was dominated by sulfate-reducers, i.e. up to 95% of H2 was used for sulfate reduction. Sulfate reduction rates of 17 mmol L(-1)d(-1) were achieved at a HRT of 3h, with over 87% of the H2 produced used for sulfate reduction. Methane production, however, persisted when operating under these conditions and increasing the HRT by returning it to values >5.5h resulted in a dominance of methanogenesis over sulfate reduction. The sulfate reduction rates were limited by the amount of CO supplied and its conversion efficiency (about 85%) at higher CO loads likely resulting from a low biomass retention. PMID- 17336365 TI - Factors affecting the fate of active proteins introduced in wastewater sludges: investigation with green fluorescent protein. AB - Green fluorescent protein (GFP) was used as a reporter protein to investigate the interactions and fate of the active conformation of proteins in wastewater sludge. GFP was chosen because its fluorescence is dependent on the integrity of its native conformation. We identified factors that cause the loss of GFP fluorescence when this protein is introduced in aerobic or anaerobic sludge. In both systems, soluble polymers present in the liquid fraction caused an initial loss of fluorescence, but stabilized the remaining fluorescent GFP molecules. In aerobic sludge, interaction of GFP with the sludge solids initially caused an additional loss of fluorescence but the remaining fluorescence kept fairly constant over the following hours. In anaerobic sludge, on the contrary, interaction of GFP with the sludge solids caused a temperature dependent loss of fluorescence, probably related to the presence of precipitated ferrous sulfide. No direct relationship was found between sludge protease activity and loss of GFP fluorescence, suggesting that proteases are not the primary factor controlling the fate of the active form of proteins in wastewater sludges. PMID- 17336366 TI - High levels of organochlorines in mothers' milk from Chennai (Madras) city, India. AB - Mothers' milk from Chennai (formerly Madras), India and three other places Perungudi, the municipal dumping site of south Chennai area (situated at the suburb of Chennai), Chidambaram, a predominantly agricultural town situated 250 km south of Chennai and Parangipettai, a fishing village 15 km north of Chidambaram, all situated at or near the southeastern Bay of Bengal coast of India were found to contain measurable concentrations of HCHs, DDTs, PCBs, CHLs and HCB. A notable finding in this study is that Chennai mothers have higher levels of HCHs in their milk and hence may transfer considerably higher amounts of the chemical than the mothers from all the other three places of the present study indicating a higher health risk to Chennai's children. It was also found that the levels of the two organochlorine pesticides (HCHs and DDTs) increased in Chennai mothers' milk in the last decade. Food items collected from Chennai markets did not show any remarkably higher levels of any of the chemicals measured in this study. Levels of the two classical organochlorines (DDTs and HCHs) have declined in many of the food items when compared with our data collected two decades before in the same locations, showing the effectiveness of the recent ban on both these chemicals in the country. The sources, possible health risks and the ways to curtail the effects of HCHs, especially at Chennai, should be investigated further. PMID- 17336367 TI - Platinum and Palladium transfer to milk, organs and tissues after a single oral administration to lactating goats. AB - Platinum (Pt) and Palladium (Pd) are massively used in catalytic converters, emitted with exhaust fumes and deposited on roadsides in particle sizes. If they are ingested by ruminants grazing in agricultural fields located along roads they may enter the food chain. The objective of this study is to assess the potential transfer of Pt (PtCl(2)) and Pd (PdCl(2)) towards milk, tissues (muscle) and organs (kidney, liver and mammary gland). Three lactating goats received orally a single dose of 200mg of Pd and 200mg of Pt at the beginning of the experiment. The milk was collected each day during eight days. On the eighth day, organs and tissues were sampled to analyse the metal concentrations by ICP-MS (quantification limit of 0.25ng/g for Pd and Pt, detection limit of 0.08ng/g). The experiment demonstrated a significant transfer of Pd and Pt to kidney. The detected concentration was, respectively, of 73.9ng/g DW and 268.5n/g DW (factor 22 and factor 73 compared to the control kidney). The amounts of metals were : in the liver,18.1ng/g DW for the Pd and 8.1ng/g DW for the Pt, in the mammary gland, 14.9ng/g DW fort the Pd and 2.5ng/g DW for the Pt and in the muscle, 4.9ng/g DW for the Pd and 0.6ng/g DW for the Pt. The Pd concentration detected in milk was higher (from 5ng/g DW to 9ng/g DW) than in control milk but the transfer factor remained very low (0.02%). The Pt in milk could not be detected because it was below the quantification limit (<0.25ng/g DW). PMID- 17336368 TI - Bioaccessible selenium in Italian agricultural soils: Comparison of the biogeochemical approach with a regression model based on geochemical and pedoclimatic variables. AB - Biogeochemical mapping of selenium in Italian agricultural soils was accomplished by measuring the Se concentration of representative samples of wheat grains from 71 provinces. The range of the concentration values averaged on a provincial basis was 7-245 ng Se g(-1). A multiple regression model based on six geochemical and pedoclimatic variables was developed to interpret the observed data and to predict Se concentration of wheat in areas where analytical data were missing and in the different Italian soil regions. The statistical model explained only part of the observed variance, but succeeded in identifying Se-enriched as well as Se depleted areas with an acceptable level of agreement with the biogeochemical map based on measured Se in wheat. Furthermore, the model showed that within the range of concentrations measured in Italian soils, Se-bioaccessibility is controlled not only by the Se content of the soil parent rocks, but also by their overall geochemical nature (carbonatic vs. silicatic) and by pedoclimatic variables (temperature and rain intensity excursions) related to fluctuations of soil moisture and pH. Overall, several Se-marginal and Se-deficient areas were identified on the Italian territory. The implications of these findings for public health are discussed briefly. PMID- 17336369 TI - Characterization of U/Pu particles originating from the nuclear weapon accidents at Palomares, Spain, 1966 and Thule, Greenland, 1968. AB - Following the USAF B-52 bomber accidents at Palomares, Spain in 1966 and at Thule, Greenland in 1968, radioactive particles containing uranium (U) and plutonium (Pu) were dispersed into the environment. To improve long-term environmental impact assessments for the contaminated ecosystems, particles from the two sites have been isolated and characterized with respect to properties influencing particle weathering rates. Low (239)Pu/(235)U (0.62-0.78) and (240)Pu/(239)Pu (0.055-0.061) atom ratios in individual particles from both sites obtained by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) show that the particles contain highly enriched U and weapon-grade Pu. Furthermore, results from electron microscopy with Energy Dispersive X-ray analysis (EDX) and synchrotron radiation (SR) based micrometer-scale X-ray fluorescence (micro-XRF) 2D mapping demonstrated that U and Pu coexist throughout the 1-50 microm sized particles, while surface heterogeneities were observed in EDX line scans. SR based micrometer-scale X-ray Absorption Near Edge Structure Spectroscopy (micro XANES) showed that the particles consisted of an oxide mixture of U (predominately UO(2) with the presence of U(3)O(8)) and Pu ((III)/(IV), (IV)/(V) or (III), (IV) and (V)). Neither metallic U or Pu nor uranyl or Pu(VI) could be observed. Characteristics such as elemental distributions, morphology and oxidation states are remarkably similar for the Palomares and Thule particles, reflecting that they originate from similar source and release scenarios. Thus, these particle characteristics are more dependent on the original material from which the particles are derived (source) and the formation of particles (release scenario) than the environmental conditions to which the particles have been exposed since the late 1960s. PMID- 17336370 TI - BAD association with membranes is regulated by Raf kinases and association with 14-3-3 proteins. PMID- 17336371 TI - On/off-regulation of phospholipase C-gamma 1-mediated signal transduction. PMID- 17336372 TI - Excess of early onset multiple myeloma in endometrial cancer probands and their relatives suggests common susceptibility. AB - OBJECTIVE: Determine whether there is an association between uterine cancer and multiple myeloma. METHODS: Data on second malignancies were obtained for 368 uterine corpus cancer patients treated between 1992 and 2005. Detailed family histories were devised for 192 probands. Diagnoses of multiple myelomas, lymphomas and leukemias in family members were medical record verified. The frequency of multiple myeloma among uterine cancer patients was compared to the female age-adjusted incidence rate of multiple myeloma obtained from the SEER database. The crude rate of multiple myeloma (as well as Hodgkin's, non-Hodgkin's lymphomas and leukemias) among first-degree relatives of patients with uterine cancer was compared to the age-adjusted incidence rate of multiple myeloma in the general population. Descriptive statistics were used to evaluate disease and cohort characteristics. A P value less than 0.05 was considered statistically significant. RESULTS: Two of 368 uterine cancer patients were also diagnosed with multiple myeloma, both at age 50. The observed incidence of multiple myeloma in this cohort (543 per 100,000; 95% CI: 66-1962 per 100,000) represents a 120-fold increase based on predicted incidence (P=0.00014). The frequency of multiple myeloma in first-degree relatives was 2/1351 (148 per 100,000; 95% CI: 14.8-533 per 100,000) which represents a 27-fold increase compared to the general population (P=0.0026). The frequencies of leukemias and lymphomas in these family members on the other hand were not significantly increased (P=0.152 and P=0.218). CONCLUSION: This specific excess frequency of early onset multiple myeloma in endometrial cancer probands and their relatives suggests shared susceptibility. PMID- 17336373 TI - Emergency Department education improves patient knowledge of coronary artery disease risk factors but not the accuracy of their own risk perception. AB - BACKGROUND: Coronary artery disease (CAD) is the single largest killer of both males and females in the United States. The Emergency Department (ED) represents a unique environment in which patient education may improve coronary artery disease risk factor knowledge and relative risk perception. ED patients' understanding of CAD risk factors is often limited. Patients' perception of their own risk is often not a reflection of their true risk. We hypothesized that an American Heart Association educational video intervention would improve patients' knowledge of coronary artery disease risk factors and personal risk awareness in the ED setting. METHODS: IRB approval was obtained for this prospective observational cohort study. Our trial included 100 adult patients (age 18 and over), both male and female, using the ED population at an inner city tertiary care Level I trauma center hospital as our source of participants. Recruitment of patients began in January 2002 and ended in May 2004. RESULTS: Patients who watched the educational video did improve their knowledge of cardiac risk factors significantly when compared to patients who received no educational video intervention. In our study, this information was not retained at 30-day follow up. However, there was still significant improvement in their knowledge when compared to baseline scores pre-intervention. Patients overestimated their risk when compared to an objective measure of risk. In both the study and control groups, patients significantly overestimated their risk pre-educational intervention, immediately post-educational intervention, and at 30-day follow-up when compared to an objective measure of risk. CONCLUSIONS: Simple educational intervention at a teachable moment (i.e. when a patient is experiencing chest pain in the ED) significantly improves patient's knowledge of CAD risk factors immediately post-intervention. This improvement in knowledge is not fully retained at 30-day follow-up, which suggests that patients may benefit from further educational intervention prior to 1 month follow-up. Patients overestimate their risk when compared to an objective measure of risk, regardless of whether they receive an educational intervention or not. PMID- 17336374 TI - Corpus luteum size and function following single and double ovulations in non lactating dairy cows. AB - Data was collated from a number of studies on various aspects of luteal function in non-lactating dairy cows to allow comparisons to be made between single and double ovulating animals. In these studies, estrous cycles had been synchronized and animals slaughtered on day 5 or 8. The overall incidence of double ovulations was 28.3%. Double ovulation was associated with smaller individual corpora lutea but no difference in total weight of luteal tissue or any aspect of luteal tissue function or plasma concentrations of progesterone. Furthermore, in a sub set of animals, there was no difference in preovulatory follicle characteristics or plasma concentrations of estradiol around ovulation. These results demonstrated a high incidence of double ovulation in non-lactating cows that had no influence on circulating progesterone concentrations. PMID- 17336375 TI - Resuspending ram spermatozoa in seminal plasma after cryopreservation does not improve pregnancy rate in cervically inseminated ewes. AB - The role of seminal plasma (SP) components on the maintenance of motility, viability and fertilising ability of frozen-thawed spermatozoa is of considerable interest. However, differences observed in constituents of SP among males could explain differences in fertility obtained in vivo. Two experiments were designed to examine the effects of seminal plasma on fertility from cervically inseminated frozen-thawed semen. The objective of Experiment 1 was to investigate if source or type of SP influences pregnancy rate. Seminal plasma was collected from rams previously classified as having either High (HSP; n=3) or Low (LSP; n=3) fertility in vivo. Artificial SP (fructose/sodium solution with 10% BSA; ASP) was made. Frozen semen from the same 6 rams was thawed and inseminated (Control) or resuspended either in HSP, LSP or ASP (20% in semen) prior to insemination of ewes (n=284, over 2 farms). The overall pregnancy rate was 28.1%. Treatments (Control, ASP, HSP and LSP) were not significantly different (P>0.3). There was no difference between HSP and LSP (P>0.5), and no effect of using ASP compared to ram SP (P>0.7), on pregnancy rate. As there was no effect of SP on pregnancy rate a repeat experiment (Experiment 2) was designed to test the effect of washing and selecting motile sperm prior to resuspending in phosphate-buffered saline (PBS) containing SP on pregnancy rate. Frozen-thawed semen from each of 2 rams was centrifuged through a density gradient, pellets were centrifuged through a wash medium and the sperm concentration/ram was counted. Sperm cells were resuspended in: (1) control PBS, (2) PBS containing 30% HSP or (3) PBS containing 30% LSP to give 100 x 10(6) motile sperm in 0.25 mL. Control straws were thawed and inseminated directly. Ewes (n=223 over 2 farms) were inseminated 57 h post-sponge withdrawal and those not returning to oestrus were slaughtered 29-50 days post insemination for pregnancy determination. In Experiment 2, the pregnancy rate for Control, PBS, HSP and LSP were 15.4%, 2.3%, 0% and 0%, respectively, for Farm 1 (P>0.05) and 17.8%, 11.0%, 3.9% and 12.4%, respectively, for Farm 2. Under the conditions of the current study, addition of SP from different donors of either High or Low fertility status to frozen-thawed ram semen post-thawing did not improve pregnancy rate in ewes. ASP had no effect on pregnancy rate in ewes when added to frozen-thawed semen. Washing and selection of motile sperm prior to resuspension in PBS with or without SP (30%) before insemination had a negative effect on pregnancy rate in cervically inseminated ewes. Hence, the addition of seminal plasma or some of its constituents to semen does not appear to improve pregnancy rate in cervically inseminated ewes. PMID- 17336376 TI - The construction of 3D-engineered tissues composed of cells and extracellular matrices by hydrogel template approach. AB - The three-dimensional (3D)-engineered tissues composed of only cells and extracellular matrices (ECM) were constructed by the hydrogel template approach. The disulfide-crosslinked poly(gamma-glutamic acid) hydrogels were prepared as a template hydrogel. These template hydrogels were easily decomposed under physiological conditions using reductants such as cysteine, glutathione and dithiothreitol by cleavage of disulfide crosslinkage to thiol groups. The decomposed polymers are soluble in cell culture medium. The cleaving of disulfide bond was determined by UV-vis and FT-IR spectroscopies. We successfully prepared the 3D-engineered tissues (thickness/diameter, 2mm/1cm) composed of mouse L929 fibroblast cells and ECM by the decomposition of only the template hydrogel with cysteine after 10 days 3D-cell culture on/in the template hydrogel. The size and thickness of the 3D-engineered tissues was completely transferred from the template hydrogel. The cultured L929 cells viability in the obtained engineered tissues was confirmed by a culture test, WST-1 method and LIVE/DEAD staining assay. The engineered tissue was self-standing and highly dense composite of the cultured cells and collagen produced by the cells. This hydrogel template approach may be useful as a new class of soft-tissue engineering technology to substitute a synthetic polymer scaffold to the ECM scaffold produced from the cultured cells. PMID- 17336377 TI - Regulation of expression and localisation of the Na+/H+ exchanger (NHE) 3 and the NHE regulatory factor 2 in baboon placental syncytiotrophoblast by oestrogen. AB - Our understanding of the regulation of the expression of the sodium hydrogen exchangers (NHE) and their regulatory factors (NHERF), which play important roles in fetal-placental homeostasis, is incomplete. We previously showed that the expression and localisation of NHE3 and NHERF2 in the juxtanuclear compartment of the placental syncytiotrophoblast were markedly decreased between mid and late baboon pregnancy. In the current study, immunocytochemical fluorescence localisation and level of NHE3/NHE1 and NHERF1/NHERF2 proteins were determined in late gestation in baboons untreated or treated throughout the second half of gestation with an aromatase inhibitor CGS 20267 alone (reduced oestrogen levels by >95%) or with oestradiol to determine whether oestrogen regulated antiporter developmental expression. The immunocytochemical expression of NHE3 and NHERF2 in the juxtanuclear compartment was minimal in baboons untreated or treated with CGS 20267 plus oestradiol (i.e. oestrogen-replete) but extensive in oestrogen suppressed animals. Moreover, the abundant expression of NHERF2 in fetal vascular endothelium of oestrogen-replete baboons was decreased in oestrogen-suppressed animals. In contrast, expression and localisation of NHE1 and NHERF1 in the placental syncytiotrophoblast were not altered by oestrogen deprivation in baboons. Based on our current and previous findings, we propose that oestrogen plays an important role in regulating localisation and expression of components of the NHE system within and consequently development and function of the primate placental syncytiotrophoblast. PMID- 17336378 TI - Lunar philosophers. AB - A close associate of the Lunar Society, Joseph Wright of Derby painted several industrial and scientific scenes. This article (part of the Science in the Industrial Revolution series) shows how two of his works - featuring an orrery and an alchemist - reveal the ideas and aspirations of the provincial philosophers who made up the Society. PMID- 17336379 TI - Arabidopsis, the botanical Drosophila: from mouse cress to model organism. AB - The small flowering plant Arabidopsis thaliana is the best-studied model organism in plant biology. More resources are allocated to research on this little weed than to the study of well-known favourites such as worms, fruit flies and mice. Yet, up to the early 1980s plant biologists had every good reason to ignore Arabidopsis: neither did it seem to possess the characteristics of a good model organism, nor did it have any agricultural promise. The sudden prestige acquired by Arabidopsis research thus constitutes a remarkable historical puzzle. What made the mouse cress into the most successful model organism to date? PMID- 17336380 TI - When water does not boil at the boiling point. AB - Every schoolchild learns that, under standard pressure, pure water always boils at 100 degrees C. Except that it does not. By the late 18th century, pioneering scientists had already discovered great variations in the boiling temperature of water under fixed pressure. So, why have most of us been taught that the boiling point of water is constant? And, if it is not constant, how can it be used as a 'fixed point' for the calibration of thermometers? History of science has the answers. PMID- 17336381 TI - Rumblings in the air: understanding earthquakes in the 1690s. AB - After a wave of earthquakes in 1692 and 1693, the astronomer John Flamsteed composed an innovative explanation of their causes. He argued that they did not originate underground but were caused by explosions of nitrous and sulphurous particles in the air. Although the idea now sounds strange, Flamsteed's account was expressed in terms that were familiar to his contemporaries in the Royal Society, drawing particularly on Boyle's chemistry and air-pressure experiments. Flamsteed was more unusual in his conviction that the earth was virtually solid; this made him an opponent of structural theories offered by Thomas Burnet, Robert Hooke and Edmond Halley. Flamsteed's ideas were dismissed by Hooke as 'nonsensicall', but by the time they were published, long after his death, they appeared closer to mainstream thinking. PMID- 17336382 TI - Making a science of literary criticism. AB - Since the emergence of "literary criticism" as a university subject in the 1880s, there have been those prepared to challenge its disciplinary status. How can something as subjective as literature be taught, let alone examined? Throughout the 20th century, the success of the sciences fostered methodological anxieties, resulting in several efforts from within the humanities to set the study of literary texts on a more scientific footing. In recent years, this scientisation of the study of literature has increasingly come from outside the humanities, as cognitive scientists and evolutionary psychologists expand their efforts to explain culture in terms of biology. So where does this leave "lit crit"? PMID- 17336383 TI - Mapping and sequencing information: the social context for the genomics revolution. AB - In 1983, after devoting some eight years of his life to the description of how a nematode worm develops from an embryo into an adult, molecular biologist John Sulston embarked on a remarkably different project: he decided to map the worm's genome. Sulston's impulsive desire to characterise this creature's DNA from start to finish offers only a partial explanation for this transition. Instead, a close examination of the wider social context for this 'moment' in molecular biology gives a more rewarding explanation of Sulston's intellectual leap. This reveals a world in which biotechnology gradually adapted to and integrated into an 'information society' increasingly dependent on the creation, distribution and manipulation of information. The application of computing to DNA during the first half of the 1980s was crucial for this integration, fostering the emergence of genomics and ultimately the Human Genome Project. PMID- 17336384 TI - Pandemic in print: the spread of influenza in the Fin de Siecle. AB - The rapid spread of the 1889-1890 influenza epidemic was widely reported in the periodical press. As Londoners read that another European capital had succumbed, they were struck that the illness was not only travelling as fast as the news, but was also moving along the same routes. Although medical science quickly resolved that a germ was the cause of the illness, its mild nature but widespread social impact lead many to suspect that it was actually caused by newspaper hype. This link between the press and the illness made the epidemic seem a curious symptom of the modern communications technologies that increasingly defined the age. PMID- 17336385 TI - Production of nitric oxide by murine peritoneal macrophages in vitro on treatment with prolactin and growth hormone: involvement of protein tyrosine kinases, Ca(++), and MAP kinase signal transduction pathways. AB - Prolactin (PRL) and growth hormone (GH) (somatotropin) have been known to possess immunomodulatory properties. In the present studies we have investigated the production of nitric oxide (NO) and TNF-alpha by murine peritoneal macrophages in vitro on treatment with PRL and GH and the signal transduction mechanism involved. It is observed that significantly enhanced production of NO is induced in macrophages on treatment with PRL and GH. It is further observed that protein tyrosine kinases, MAP kinases and Ca(++) channeling are involved in NO production by macrophages on in vitro treatment with PRL and GH. GH and PRL induced nitric oxide did not have any effect on the expression and production of TNF-alpha. PRL or GH induced TNF-alpha production by murine macrophages was insensitive in the presence of competitive inhibitor of NOS, L-NMMA. Similarly, there is no autocrine or paracrine effect of TNF-alpha on GH or PRL induced NO production and iNOS expression. PMID- 17336386 TI - Nucleotide excision repair in an immunoglobulin variable gene is less efficient than in a housekeeping gene. AB - Immunoglobulin variable genes undergo several unusual genetic modifications to generate diversity, such as gene rearrangement, gene conversion, somatic hypermutation, and heavy chain class switch recombination. In view of these specialized processes, we examined the possibility that variable genes have intrinsic characteristics that allow them to be processed differently in the course of basic DNA transactions as well. This hypothesis was studied in an experimental system to gauge the relative efficiency of a DNA repair pathway, nucleotide excision repair, on a variable gene and a housekeeping gene. DNA damage was induced by ultraviolet light in murine hybridoma B cells, and repair was measured over time by an alkaline Southern blot technique, which detected removal of cyclobutane pyrimidine dimers. The rate of DNA repair in a rearranged variable gene, V(H)S107, was compared to that in the dihydrofolate reductase gene. Although both genes were actively transcribed, the V(H)S107 gene was repaired less efficiently than the dihydrofolate reductase gene. These results suggest that variable genes have inherent properties that affect the efficiency of nucleotide excision repair. PMID- 17336387 TI - CD8+ T lymphocytes specific for glutamic acid decarboxylase 90-98 epitope mediate diabetes in NOD SCID mouse. AB - During the past decade, glutamic acid decarboxylase (GAD) has been considered a crucial beta-cell autoantigen involved in type 1 diabetes in the NOD mouse and human. Recently, the etiological role of GAD has remained controversy. In the NOD mouse, some previous studies argued in favor of a regulatory role for GAD specific CD4+ T cells, and no diabetogenic CD8+ T cells specific for GAD have been identified so far, discrediting the importance of GAD in beta-cell injury. Here, we identified, in the NOD model, a relevant GAD CD8+ T cell epitope (GAD(90 98)) using immunization with a plasmid encoding GAD, a protocol relying on in vivo processing of peptides from the autoantigenic protein. In pancreatic lymph nodes of naive female NOD mice, CD8+ T lymphocytes recognizing GAD(90-98) peptide were detected during the initial phase of invasive insulitis (between 4 and 8 weeks of age), suggesting an important role for these cells in the first stage of the disease. GAD(90-98) specific CD8+ lymphocytes lysed efficiently islet cells in vitro and transferred diabetes into NOD(SCID) mice (100%). Finally, diabetes was accelerated greatly in 3-week-old female NOD mice injected i.p. with GAD(90 98), strengthening the role of GAD-specific CTLs in diabetes pathogenesis. PMID- 17336388 TI - Ap4A is not an efficient Zn(II) binding agent. A concerted potentiometric, calorimetric and NMR study. AB - Diadenosine 5',5''-P(1)P(4) tetraphosphate (Ap(4)A) has been considered as an intracellular partner for Zn(II). We applied potentiometry, ITC and NMR to study protonation equilibria of Ap(4)A and Zn(II) complexation by this dinucleotide. The values of binding constants obtained by these three techniques under various experimental conditions coherently demonstrated that Ap(4)A binds Zn(II) weakly, with an apparent binding constant of ca. 10(4) at neutral pH. Such a low stability of Zn(II) complexes with Ap(4)A excludes a possibility for interactions between these two agents in vivo. PMID- 17336389 TI - Toll-like receptor 4 siRNA attenuates LPS-induced secretion of inflammatory cytokines and chemokines by macrophages. AB - Toll-like receptor 4 (TLR4) is critical for activation of macrophages by Lipopolysaccharide (LPS). In this study, we investigated the silencing effects of TLR4-specific 21-nt small interfering RNAs (siRNA) on TLR4 expression in RAW264.7 cells. It was found that treatment with TLR4 siRNA down-regulated the TLR4 mRNA and protein expression in macrophage RAW264.7 cells, and reduced the sensitivity of the cells to LPS stimulation. Our findings also demonstrate that treatment with TLR4 siRNA significantly decreased the tumor necrosis factor-alpha (TNF alpha) and macrophage inflammatory protein 2 (MIP-2) expression induced by LPS. TLR4 siRNA treatment also impaired the signalling of mitogen-activated protein kinases (MAPK) induced by LPS in RAW264.7 cells. These data suggest that inhibition of TLR4 expression by TLR4 siRNA may be therapeutically beneficial in controlling the overall responses of immune cells to LPS. PMID- 17336391 TI - New display of the timing and firing frequency of single motor units. AB - The neural control of important rhythmical processes such as breathing and locomotion is complex. It is often necessary to depict the activity of motor (or other) units throughout the cycles. We describe and illustrate a novel method that displays visually seven key variables in a single figure related to the timing and frequencies of the discharge of single motor units. This time-and frequency plot (TAFPLOT) displays the recruitment time, time of peak discharge frequency and derecruitment time, as well as the onset, peak, and final firing frequencies of each motor unit in a population. The frequency of any tonic firing is also displayed. Using the TAFPLOT it is easy to identify the presence or absence of coordinated activity within and between different motoneuron pools. The method is used to illustrate novel differences in the discharge behavior between populations of single motor units innervating the human diaphragm and genioglossus muscles. This new display provides a simple, qualitative and quantitative tool to study the neural control of rhythmical or repetitive motor tasks. PMID- 17336390 TI - Structure-nongenomic neuroprotection relationship of estrogens and estrogen derived compounds. AB - Nongenomic estrogen signaling pathways involve extranuclear estrogen receptors or function independently from estrogen receptors. These pathways participate in neuroprotection elicited by the hormone. Additional nongenomic neuroprotective effects are attributable to antioxidant and antiinflammatory actions of estrogens. Numerous chemical modifications to afford neuroprotective compounds from estrogens while eliminating estrogenicity and maintaining or enhancing nongenomic neuroprotection have been described. This review highlights recent structure-activity studies that revealed the importance of antioxidant effects for neuroprotective estrogen analogues and derivatives. PMID- 17336392 TI - Optimization of wavelets for classification of movement-related cortical potentials generated by variation of force-related parameters. AB - The paper presents a novel pattern recognition approach for the classification of single-trial movement-related cortical potentials (MRCPs) generated by variations of force-related parameters during voluntary tasks. The feature space was built from the coefficients of a discrete dyadic wavelet transformation. Mother wavelet parameterization allowed the tuning of basis functions to project the signals. The mother wavelet was optimized to minimize the classification error estimated from the training set. Classification was performed with a support vector machine (SVM) approach with optimization of the width of a Gaussian kernel and of the regularization parameter. The efficacy of the optimization procedures was representatively shown on electroencephalographic recordings from two subjects who performed unilateral isometric plantar flexions at two target torques and two rates of torque development. The proposed classification method was tested on four pairs of classes corresponding to the change in only one of the two parameters of the task. Misclassification rate (test set) in the classification of 1-s EEG activity immediately before the onset of the tasks was reduced from 50.8+/-2.9% with worst wavelet and nearest representative classifier, to 40.2+/ 7.3% with optimal wavelet and nearest representative classifier, and to 15.8+/ 3.4% with optimal wavelet and SVM with optimization of the kernel and regularization parameter. The proposed pattern recognition method is promising for classification of MRCPs modulated by variations of force-related parameters. PMID- 17336393 TI - Molecular cloning and functional analysis of goose interferon gamma. AB - The cDNA for goose interferon gamma (goIFN-gamma) was cloned from PHA-stimulated goose peripheral blood mononuclear cells (PBMCs) by RT-PCR. This cDNA encodes a 19-amino acid signal peptide and a 145-amino acid mature protein, which shares a high homology with duck IFN-gamma. Recombinant mature goose interferon gamma (rgoIFN-gamma) generated from both prokaryotic and eukaryotic expression systems effectively inhibited the replication of goose paramyxovirus and recombinant vesicular stomatitis virus in vitro. These antiviral activities were abrogated by rabbit anti-rgoIFN-gamma antibodies in vitro. Furthermore, rgoIFN-gamma stimulated goose peritoneal macrophages to produce nitric oxide (NO) in vitro, demonstrating its macrophage activating factor (MAF) activity. Therefore, the availability of bioactive rgoIFN-gamma and its specific antibodies provides valuable tools for studying T cell immunity in geese. PMID- 17336394 TI - Distinct tissue cytokine and chemokine mRNA expression in canine sino-nasal aspergillosis and idiopathic lymphoplasmacytic rhinitis. AB - Idiopathic lymphoplasmacytic rhinitis (LPR) and sino-nasal aspergillosis (SNA) are among the most common causes of nasal discharge in dogs. The pathogenesis of both diseases is poorly understood. Some have proposed that LPR is a chronic inflammatory response to an inhaled irritant, pollutant or allergen, but others suggest that most cases of LPR constitute undiagnosed cases of SNA. Local immune dysfunction is thought to permit opportunist infection in canine SNA. This study investigates the nature of the local tissue immune response mounted in canine LPR and SNA in order to determine whether these diseases have similar or distinct pathogenesis. Quantitative reverse transcriptase polymerase chain reaction was carried out on RNA isolated from nasal biopsies from diseased and control dogs, using specific assays designed to amplify messenger RNA (mRNA), encoding a panel of cytokines and chemokines. SNA was associated with significantly increased expression of mRNA encoding interleukin (IL)-6, IL-8, IL-10, IL-12p19, IL-12p35, IL-12p40, IL-18, IFN-gamma, TNF-alpha, TGF-beta, eotaxin-2 and all four monocyte chemoattractant proteins (MCPs) relative to controls. LPR was associated with significantly increased expression of mRNA encoding IL-5, IL-8, IL-10, IL-12p19, IL-12p40, IL-18, TNF-alpha, TGF-beta, MCP-2 and MCP-3 relative to controls. There was significantly more expression of mRNA encoding IL-6, IL-8, IL-10, IL-12p35, IL-12p40, IL-18, IFN-gamma, TNF-alpha, TGF-beta and all MCPs, and significantly less expression of IL-5 in dogs with SNA than in dogs with LPR. Thus, the profile of cytokine and chemokine gene expression in the nasal mucosa is different in dogs with LPR when compared to dogs with SNA. A partial Th2 immune response appears to be mounted in the nasal mucosa of dogs with LPR, whereas the mucosal immune response in canine SNA is of the Th1 type. Increase in IL-10 and TGF-beta transcripts in dogs with SNA is thought to be implicated in the failure to clear the Aspergillus infection. These results constitute the first evidence that the pathogenesis of canine LPR and SNA is distinct. PMID- 17336395 TI - Characterisation of bovine inducible nitric oxide synthase. AB - Inducible nitric oxide (iNOS) is an enzyme that catalyzes the production of the reactive nitrogen intermediate nitric oxide (NO). NO is an important signalling molecule, released by numerous cells, that acts in many tissues to regulate a diverse range of physiological and biological processes, including neurotransmission, immune defence and the regulation of cell death (apoptosis). NO plays a major role in the killing of intracellular pathogens as part of the innate immune response. iNOS is known to be induced by a number of stimuli including cytokines as well as pathogens and their components. As yet, a full length bovine iNOS sequence has only been predicted from the genome, although partial sequences from cDNA are available. Here, we have identified a 3471bp transcript for bovine iNOS, isolated from RNA from bovine alveolar macrophages stimulated with the intracellular pathogen Mycobacterium bovis. When translated this gives a protein of 1156 amino acids. Bovine iNOS shows a high degree of similarity to iNOS from other species, and also shares a common protein domain structure. PMID- 17336396 TI - Hu and Yo antibodies have heterogeneous avidity. AB - Onconeural antibodies such as anti-Hu and anti-Yo may be important in the pathogenesis of paraneoplastic neurological syndromes. The avidity of these antibodies is not known. In this study, we compared the avidity of Hu and Yo antibodies both at single time points and over a time range of 2 months to 6 years. The avidity of Yo and Hu antibodies differed among the patients, but anti Yo generally had higher avidity than anti-Hu. Whether Yo antibodies are more pathogenic than Hu antibodies are presently unknown. PMID- 17336397 TI - Multiple sclerosis and anti-Plasmodium falciparum innate immune response. AB - Several epidemiological investigations conducted in Sardinia, insular Italy, indicate that the strong selective pressure of malaria along the centuries may have concurred to the elevated genetic MS-risk in this region. To test such hypothesis in an experimental setting, we have compared the immune response to P. falciparum (the causative agent of malaria) in Sardinian MS patients relative to their ethnic healthy controls and control MS patients of different ethnicity. To this purpose, the P. falciparum-driven peripheral mononuclear cell proliferation, the production of pro-inflammatory cytokines of the innate immunity such as TNF alpha, IL-6 and IL-12 and the ability to inhibit the parasite growth have been tested in relation to HLA-DR alleles and TNF promoter polymorphisms known of being associated to MS. We found that P. falciparum-induced proliferation, cytokine production and parasite killing are significantly augmented in Sardinian MS patients as compared to controls (p<0.01). Additionally, a correlation is found with genes associated to Sardinian MS, namely the TNF(-376A) promoter polymorphism and the class II HLA-DRB1*0405 allele. In conclusion, we have found evidences that some genetic traits formerly selected to confer a protective responses to P. falciparum now partially contribute to the elevated MS susceptibility amongst Sardinians. PMID- 17336398 TI - Pediatric sialolithiasis: what is different from adult sialolithiasis? AB - OBJECTIVE: To investigate the clinical characteristics of pediatric sialolithiasis, which are distinct from those of adult sialolithiasis. METHODS: A total of 210 patients with sialolithiasis confirmed by surgical treatment were enrolled in the study from Samsung Medical Registry (1995-2005). Twenty-nine were pediatric patients (age < or =18 years) and 181 adult patients (age >19 years). Comparison of pediatric and adult sialolithiasis was performed in terms of subject characteristics, clinical manifestations, salivary calculi characteristics, treatment modalities and outcomes. RESULTS: Postprandial recurrent swelling was the most frequent complaint in pediatric sialolithiasis patients, as similar as in adult patients. However, duration of symptoms was shorter in pediatric patients (mean 14.1 months versus 30.7 months, P=0.003). Most calculi were less than 1cm in pediatric patients (93.1%), compared to 56.3% of the adult patients (P=0.001). The calculi were located more in the distal duct (62.0%) than in proximal duct and gland in the pediatric patients, whereas 44.7% in the adult patients (P=0.038). CONCLUSION: Because of large proportion of relatively small and distal sialolithiasis in pediatric patients, bimanual careful palpation of the oral cavity is mandatory to diagnostic approach for children suspicious of sialolithiasis. These findings also suggest that intra oral approach is effective treatment procedure for most of sialolithiasis in children. PMID- 17336399 TI - Using RT-prone recombination to promote re-building of complete retroviral vectors from two defective precursors: low efficiency and sequence specificities. AB - Retroviral recombination has been suggested as a useful way to modify retroviral vectors. The possibility to combine two multiply deleted retroviral vectors into a novel vector was evaluated. To investigate this possibility we have constructed two defective vectors containing a shared internal ribosome entry site (IRES). The IRES was selected for its complex secondary structure, a feature described to favour retroviral recombination. The IRES was expected to promote a recombination event leading to the formation of a unique, functional retroviral vector. By supporting expression of two transgenes from a single promoter, this sequence was also expected to allow straightforward detection of the recombination event. The present data confirms the achievement of recombination-dependent rescue, albeit at low efficiency. Unexpectedly, a preferential use of the packaging signal (Psi) for recombination was observed, as compared to the IRES. Together these observations mitigate the idea of using this technique for the design of retroviral vectors. PMID- 17336400 TI - Development of an epitope-blocking-enzyme-linked immunosorbent assay to differentiate between animals infected with and vaccinated against foot-and-mouth disease virus. AB - An epitope-blocking ELISA (EB-ELISA) was developed to distinguish animals infected with foot-and-mouth-disease (FMDV) from those immunized with commercial vaccines. The assay used monoclonal antibodies to target the 3B core repeat motif (QKPLK) and purified recombinant 3AB proteins from the major B cell line epitopes of FMDV. Sera from uninfected and regularly vaccinated cattle, pigs, goats, and sheep (raised in FMDV free areas) were screened to evaluate the specificity of the EB-ELISA. The specificity scores of the assays were 99.8-100% and 100%, respectively. Reference sera from cattle, pigs, goats, and sheep experimentally infected with FMDV tested positive, with only a single exception. Antibodies formed in response to FMDV 3B appeared 1 week after infection and persisted at high levels for more than 8 weeks within the sera collected from serial bleeding of animals infected with FMDV O/SKR/2000. The EB-ELISA was used to differentiate between farms vaccinated against and those infected with FMDV (FMDV Asia serotype) during the 2005 epidemic in Mongolia by detecting antibodies against the FMDV Asia serotype in outbreak farms. This EB-ELISA method shows promise as an effective tool for FMDV control and eradication. PMID- 17336402 TI - Comparison of pp65 antigenemia, quantitative PCR and DNA hybrid capture for detection of cytomegalovirus in transplant recipients and AIDS patients. AB - The cytomegalovirus (CMV) antigenemia assay has been used frequently for rapid diagnosis of CMV infection, and antigenemia threshold values are recommended for triggering preemptive therapy. Hybrid capture of CMV's DNA and quantitative polymerase chain reaction (qPCR) are increasingly being adopted for early detection of CMV. The performance of the antigenemia assay, qPCR in plasma and hybrid capture in leukocytes were compared in 110 immunocompromised patients (38 bone-marrow transplants, 50 renal transplants and 22 AIDS patients). The most sensitive test was hybrid capture for transplants, while antigenemia and the qPCR showed similar performance for patients with AIDS. QPCR and hybrid capture thresholds requiring antiviral therapy were calculated using a receiver-operating characteristic curve for antigenemia values corresponding to 2 positive cells for bone-marrow transplants and to 10 positive cells for renal transplants and AIDS patients. These threshold values varied with the group of patients considered, with corresponding sensitivities higher than 86% and specificities higher than 76% for hybrid capture, and sensitivities higher than 61% and specificities higher than 75% for qPCR in plasma. Hybrid capture in leukocytes can substitute for antigenemia in the case of transplants, and qPCR in plasma can substitute for it in the case of AIDS patients. PMID- 17336401 TI - Using improved technology for filter paper-based blood collection to survey wild Sika deer for antibodies to hepatitis E virus. AB - Recent reports from Japan implicated wild Sika deer (Cervus nippon) in the zoonotic transmission of hepatitis E to humans. Seroprevalence studies were performed to determine if imported feral populations of Sika deer in Maryland and Virginia posed a similar risk of transmitting hepatitis E virus (HEV). Hunters collected blood on filter paper discs from freshly killed deer. The discs were desiccated and delivered to a collection point. The dried filters were weighed to estimate the amount of blood absorbed and were eluted and collected in one tube via a novel extraction system. The procedure was quantified and validated with negative and positive serum and blood samples obtained from domestic Sika deer before and after immunization with HEV recombinant capsid protein, respectively. None of the 155 tested samples contained antibody to HEV, suggesting that Sika deer in these populations, unlike those in Japan, do not pose a significant zoonotic threat for hepatitis E. However, the new method developed for collecting and eluting the samples should prove useful for field studies of many other pathogens. PMID- 17336403 TI - The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior. AB - Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10 microg estradiol benzoate and 500 microg progesterone. Sexually receptive females were infused bilaterally with 200 ng of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8 OH-DPAT), or with a combination of 200 ng 8-OH-DPAT and 2000 ng of the 5-HT(2) receptor agonist, (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI). 8-OH DPAT inhibited lordosis behavior and DOI reduced this inhibition. However, if females were preinfused with the PKC inhibitor, bisindolymaleimide I hydrochloride (BIM), DOI's effect was eliminated. BIM's attenuation of the effects of DOI was time-dependent. When BIM was infused 90 min, but not 30 min, before the 5-HT receptor agonists, BIM eliminated DOI's protection against the lordosis-inhibiting effects of 8-OH-DPAT. A concentration of BIM as low as 10(-5) nmol in a 0.5 microl infusion volume was effective and there was little evidence of dose responsivity between 10(-5) and 10(-1) nmol of BIM. In contrast, prior infusion with vehicle or with 10(-7) nmol BIM had no impact on the female's response to the 5-HT receptor agonists. These findings allow the suggestion that DOI's ability to increase PKC may be responsible for attenuation of the effects of 8-OH-DPAT on lordosis behavior. PMID- 17336405 TI - Ultrasonic vocalizations emitted during dyadic interactions in female mice: a possible index of sociability? AB - Despite the evidence that ultrasonic vocalizations are a consistent component of the behavioural repertoire of female mice, only few studies have investigated this phenomenon. In this paper, we reported new data about ultrasonic vocalisations emitted during female-female mice social encounters. In particular, we first showed that the resident female utters a considerable number of 70 kHz calls and that the number of calls seems to be modulated by the motivational state of the emitter during the estrous cycle: sexually receptive females emitted fewer ultrasonic vocalizations than non-receptive ones in the presence of a female intruder. A strong positive correlation linked the number of calls and the time spent by the resident sniffing the intruder female. Moreover, the number of calls uttered during interaction with an unknown female partner significantly decreased with pregnancy and ageing. Secondly we reported that 1-year-old female mice showed a reduction of ultrasonic calls in the presence of a partner they had been exposed to, only if the re-exposure (test) occurred 30 min after the previous presentation. If the test was performed with a delay of 60 min, the number of calls emitted did not decrease. These results confirm that ultrasonic vocalizations emitted during social interaction with a female conspecific can be used as an index of social recognition and can be useful to detect age-related disruption of social memory in female mice. PMID- 17336404 TI - Hippocampal-parietal cortex interactions: evidence from a disconnection study in the rat. AB - The goal of the present experiments was to use a disconnection paradigm to test the interactions between the hippocampus and parietal cortex (PC) during an object-place paired associate learning task, dry-land water maze task, and a reaction-to-change task. Previous research indicates that these tasks are sensitive to hippocampal or PC disruption. Unilateral lesions were made to the dorsal hippocampus or posterior PC in contralateral hemispheres or ipsilateral hemispheres. It was hypothesized that if the hippocampus and PC interact, then contralateral lesioned animals should be markedly impaired compared to ipsilateral lesions. The results indicate that contralateral lesioned animals were significantly more impaired than animals with ipsilateral lesions during object-place paired-associate learning; however, both groups readily learned single discriminations (i.e., objects or places). Furthermore, contralateral lesioned animals traveled further to find the reward during acquisition of the dry-land water maze task and spent less time in the rewarded quadrant during the probe trial. Conversely, contralateral lesioned animals' performance matched ipsilateral lesioned animals during the reaction-to-change paradigm. Thus, the hippocampus and PC interact during some tasks, presumably when tasks require multiple trials across days, but not during the detection of novelty within a single day. PMID- 17336406 TI - Congenital pulmonary vein stenosis beyond childhood. AB - We report a case of anomalous connection of pulmonary veins with insertional stenoses causing undiagnosed severe pulmonary hypertension in a 37-year-old woman. We report the use of non-invasive diagnostic investigations in making the diagnosis, and the apparent cure of this rare condition with resolution of right heart failure following surgical treatment. PMID- 17336407 TI - Cytokines in HIV-associated cardiomyopathy. AB - Among the multiple cardiac manifestations occurring in HIV-infected patients, cardiomyopathy is one of the most challenging. Its incidence has only slightly decreased since the introduction of highly active antiretroviral therapy (HAART). Also, its pathogenesis remains relatively unclear. Although several studies demonstrated the presence of HIV genome in the heart of patients, more recent developments found that viral infection plays an indirect role only, as well as they recognized the contribution of proinflammatory cytokines in the progression of the disease. Experimental studies on animals and cultured myocytes have established the signalling pathway triggered by proinflammatory cytokines in heart failure and cardiomyopathy. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6 promote expression of inducible nitric oxide synthase (iNOS) in cardiomyocytes through activation of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappaB (NFkappaB). TNF-alpha and high concentrations of NO also induce cardiomyocyte apoptosis by TNF type 1 receptor activation. This biological framework, which is also involved in progression of cardiomyopathy in humans, is more pronounced in HIV-infected patients, in whom proinflammatory cytokines TNF-alpha, IL-1 and IL-6 are increased, resulting in an enhanced expression of cardiac iNOS, especially in patients with a low CD4 T cell count. This may account for the worse outcome of heart failure in HIV-infected patients. However, there are only few data today to support future therapeutic implications of cytokines antagonism in treatment of HIV-infected patients with cardiomyopathy. Whether modulation of TNF production or selective inhibition of p38 MAPK pathway could be useful approaches remains uncertain. PMID- 17336408 TI - Successful percutaneous treatment of an intraprocedural left main stent thrombosis with the support of an automatic mechanical chest compression device. PMID- 17336409 TI - Entrapped catheter in the left ventricular posterior venous radicle of the coronary sinus in a case of hemianomalous pulmonary venous connection of left pulmonary veins to coronary sinus. AB - A 25-year old acyanotic lady with unclear pulmonary venous drainage and a dilated coronary sinus was catheterized. Left pulmonary veins drained into coronary sinus in a left pulmonary vein angiogram done through the coronary sinus with a National Institute of Health 7F catheter. After the angiogram, the catheter got entrapped in a coronary sinus tributary and could be removed only by surgery. The left pulmonary veins were rerouted into the left atrium by unroofing the coronary sinus. Surgery is the treatment of choice for entrapped catheters when the primary condition itself merits surgical correction. PMID- 17336410 TI - Extensive exfoliative dermatitis induced by non-ionic contrast medium Iodixanol (Visipaque) used during percutaneous coronary intervention. AB - We report a case of extensive exfoliative dermatitis in a patient appearing 3 days after intracoronary administration of non-ionic contrast medium Iodixanol (Visipaque) during the primary percutaneous coronary intervention. The patient presented with acute myocardial infarction and has never exposed to any X-ray contrast medium. The patient was successfully treated with corticosteroid, antihistamines and antibiotics for the prevention of secondary bacterial infection. The patient was recovered 8 days after the anti-allergic medical management. This case can be a rare example of late-onset allergic reaction to a non-ionic contrast medium Iodixanol presented with extensive exfoliative dermatitis. PMID- 17336411 TI - Anti-muscarinic autoantibodies and vagal modulation in Chagas disease: positive allosteric modulators vs desensitization and downregulation of M2 cardiac acetylcholine receptors. PMID- 17336412 TI - Isolated left ventricular noncompaction in association with rheumatic mitral stenosis. AB - Fifty year old man with a known case of chronic rheumatic heart disease with atrial fibrillation was presented with severe mitral stenosis. He was incidentally detected to have noncompaction of left ventricle on echocardiography and Doppler examination. He underwent successful percutaneous trans-luminal mitral commissurotomy (PTMC) for severe mitral stenosis. This is the first reported case of isolated ventricular noncompaction (IVNC) associated with acquired chronic rheumatic mitral stenosis. PMID- 17336413 TI - Prevalence of Salmonella antibodies among goats slaughtered for chevon in Bareilly (Northern India). AB - We screened serum samples of 1024 goats slaughtered for chevon in Bareilly in Northern India for Salmonella antibodies with indirect ELISA, MAT-H (microagglutination test using flagellar antigens e, n, x and 1, 5) and MAT-O (microagglutination test using somatic antigens 4, 12 and 3, 10, 15). Salmonella antibodies were detected in 48, 8 and 40%, goats using Salmonella-cytotoxi-I ELISA, MAT 'H' and MAT 'O', respectively. After adjusting for test accuracy, the seroprevalence were highest for Salmonella-cytotoxi-I ELISA (46%) followed by agglutinins against 'O' 3, 10, 15 (15%) and negligible for other agglutinins. With all 5 tests, prevalence of Salmonella antibodies was significantly higher in females than in males. No significant difference was evident in prevalence of Salmonella antibodies to different antigens in different age groups of male goats except for e, n, x agglutinins that were significantly more prevalent in young adult (<6-18 months) males than in adult (>18 months of age) or young (< or =6 months of age) goats. On the other hand, in females, prevalence of Salmonella cytotoxin-I antibodies and e, n, x agglutinins differed significantly among three age groups, being the most prevalent in adult goats. As expected, the results of different tests had little or no correlation because the different tests targeted antibodies to different antigens. PMID- 17336414 TI - Citations of plenary-session articles published in the Proceedings of the International Symposium on Veterinary Epidemiology and Economics. AB - We measured the potential impact of articles representing the International Symposium on Veterinary Epidemiology and Economics (ISVEE) plenary-session presentations in subsequent published literature. Between July 1, 2004 and November 9, 2004, we searched the Web of Science for citations in the scientific literature to all 99 plenary-session articles published in the proceedings of the previous nine ISVEEs (or in journal special issues dedicated to the ISVEE plenary articles). We used a 4-year window around the publication of each of the ISVEE proceedings. We located 187 citations for 37 (of the 99) articles. We infer that the ISVEE proceedings represent an important resource for veterinary epidemiology. PMID- 17336415 TI - Release of cell wall polysaccharides from Saccharomyces cerevisiae thermosensitive autolytic mutants during alcoholic fermentation. AB - In order to increase the release of cell wall polysaccharides during alcoholic fermentation, a wine strain of Saccharomyces cerevisiae was subjected to UV mutagenesis to obtain thermosensitive autolytic mutants affected in cell wall integrity. Five mutants and the parental strain were utilized in fermentation trials conducted at 28, 32 and 34 degrees C. Results showed that at all temperatures the mutant strains released into the medium a higher polysaccharide quantity than the parental strain. In particular, at 28 degrees C there was a doubling of these macromolecules. At the end of alcoholic fermentation, all strains showed at 28 degrees C elevated and similar levels of viable cells; at 32 degrees C this parameter remained high for mutant strains ts16 and ts39 and the parental strain; at 34 degrees C all strains underwent a drop in cell viability, which was less intense in the case of strain ts16. As a relationship between cell viability and the quantity of polysaccharides released by the yeast strain was not found, it can be assumed that the mutation led to cells with a less stable wall and thus an easier release of macromolecules into the medium. PMID- 17336416 TI - T cell receptor excision circles (TRECs) analysis during acute intrarectal infection of cynomolgus monkeys with pathogenic chimeric simian human immunodeficiency virus. AB - Several studies have shown the importance of evaluating Recent Thymic Emigrants (RTEs) by quantification of T cell receptor-rearrangement excision circles (TRECs), as a measure of de novo T cell generation during human immunodeficiency virus-1 (HIV-1) infection. To determine whether acute viral infection may have an impact on TRECs, cynomolgus monkeys (Macaca fascicularis) were infected intrarectally with simian human immunodeficiency virus (SHIV) 89.6P(cy11) and the number of signal-joint (sj) TRECs was determined in purified CD4+ and CD8+ populations for up to 28 weeks post-infection. Four weeks after infection, TRECs levels significantly decreased in both CD3+ CD4+ and in CD3+ CD8+ T lymphocytes of infected monkeys, whereas they remained unchanged in uninfected animals. This reduction was followed by a progressive TRECs number recovery in CD3+ CD4+ T lymphocytes that positively correlated with changes in the levels of circulating CD3+ CD4+ T cells. In the CD3+ CD8+ T cell subset, TRECs number remained significantly low and inversely correlated with the increase in the percentages of CD3+ CD8+ T cells. These data suggest that SHIV89.6P(cy11) intrarectal infection of cynomolgus monkeys differently affects TRECs content in CD3+ CD4+ and CD3+ CD8+ T cell subsets. PMID- 17336417 TI - AT1 receptor antagonist Candesartan in selected cirrhotic patients: effect on portal pressure and liver fibrosis markers. AB - BACKGROUND/AIMS: The renin-angiotensin system plays an important role in hepatic fibrogenesis and in portal hypertension. To examine the long-term effects of Candesartan cilexetil, an angiotensin type 1 (AT1) receptor blocker, on portal systemic haemodynamics and on liver fibrosis. METHODS: Forty-seven compensated Child A and Child B (8) cirrhotic patients were randomly assigned to receive Candesartan cilexetil, 8 mg/d (N.24) and no treatment (N.23) for 1 year. Portal systemic haemodynamic parameters, serological levels of procollagen (PIIINP), hyaluronic acid (HA) and transforming growth factor beta 1 (TGFbeta1) were assessed at baseline and after 12 months. RESULTS: No patients discontinued or decreased the drug. The hepatic venous pressure gradient (HVPG) decreased significantly in treated patients (-8.4%+/-2.4) with a reduction >20% in 25% of cases vs+5.6%+/-2.9 in the untreated group. HA plasma levels decreased significantly in Candesartan treated patients in whom HVPG diminished and rose in untreated patients in whom HVPG increased. CONCLUSIONS: In selected cirrhotic patients, pharmacological inhibition of the AT1 receptor is well tolerated and induced a mild reduction of portal pressure. This haemodynamic effect might be related to liver fibrogenesis activity. PMID- 17336418 TI - The role of estrogen receptor subtypes in ameliorating hepatic injury following trauma-hemorrhage. AB - BACKGROUND/AIMS: The aim of this study was to determine which of the estrogen receptor (ER) subtypes plays a predominant role in ameliorating hepatic damage following trauma-hemorrhage. METHODS: Adult male rats were subjected to hemorrhagic shock (40 mmHg for 90 min) and resuscitation. ER-alpha agonist (PPT) or ER-beta agonist (DPN) was administered during resuscitation; rats were sacrificed 24h thereafter. RESULTS: PPT or DPN decreased elevated plasma alpha glutathione S-transferase levels; however, PPT was more effective. PPT or DPN increased hepatic heat shock protein 32 (Hsp32) mRNA/protein expressions above levels observed after trauma-hemorrhage. PPT reduced hepatic NF-kappaB and AP-1 activity and iNOS expression. Although DPN reduced hepatic NF-kappaB activity, AP 1 activity remained higher than in shams; hepatic iNOS induction remained elevated. PPT/DPN reduced nitrate/nitrite production and iNOS mRNA in Kupffer cells following trauma-hemorrhage; however, these levels in DPN-treated animals remained higher than sham. CONCLUSIONS: Although both PPT and DPN decreased hepatic injury following trauma-hemorrhage, ER-alpha agonist PPT appears to be more effective in downregulating NF-kappaB and AP-1 activity, and iNOS induction. Thus, ER-alpha appears to play a predominant role in mediating the salutary effects of E2 in ameliorating hepatic damage following trauma-hemorrhage. PMID- 17336419 TI - Worldwide mortality from cirrhosis: an update to 2002. AB - BACKGROUND/AIMS: Cirrhosis mortality has registered large changes over the last few decades. METHODS: Age-standardized (world standard) cirrhosis mortality rates per 100,000 were computed for 41 countries worldwide over the period 1980-2002 using data from the WHO mortality database. RESULTS: In the early 1980s, the highest rates were in Mexico, Chile (around 55/100,000 men and over 14/100,000 women), France, Italy, Portugal, Austria, Hungary and Romania (around 30 35/100,000 men and 10-15/100,000 women). Mortality from cirrhosis has been steadily declining in most countries worldwide since the mid or late 1970s (annual percent change, APC, between -5% and -1.5% in the last decade only for both sexes). In southern Europe, rates in the early 2000s were less than halved compared to earlier decades. In contrast, rates have been rising in Eastern European countries to reach extremely high values in the mid 1990s, and declined only thereafter. In the UK rates were still steadily rising (APC around +7% in men and +3% in women from England and Wales, and +9% in men and +7% in women from Scotland). CONCLUSIONS: Mortality from cirrhosis shows favourable trends in most countries of the world, following the reduction in alcohol consumption and hepatitis B and C virus infection. The steady upward trends observed over more recent calendar periods in the UK and central and eastern European countries are attributed to the persistent increase in the prevalence of alcohol consumption. PMID- 17336420 TI - Accumulation of proteins bearing atypical isoaspartyl residues in livers of alcohol-fed rats is prevented by betaine administration: effects on protein-L isoaspartyl methyltransferase activity. AB - BACKGROUND/AIMS: Protein-L-isoaspartyl methyltransferase (PIMT) is a methyltransferase that plays a crucial role in the repair of damaged proteins. In this study, we investigated whether ethanol exposure causes an accumulation of modified proteins bearing atypical isoaspartyl residues that may be related to impaired PIMT activity. We further sought to determine whether betaine administration could prevent the accumulation of these types of damaged proteins. METHODS: Livers of male Wistar rats, fed the Lieber DeCarli control, ethanol or 1% betaine-supplemented diets for 4 weeks, were processed for PIMT-related analyses. RESULTS: We observed a significant increase in the accumulation of modified proteins bearing isoaspartyl residues, i.e. the substrates for PIMT, in homogenate samples and various subcellular fractions of livers from ethanol-fed rats. Betaine supplementation prevented this accumulation of damaged proteins. In contrast, ethanol exposure induced no changes in the PIMT enzyme activity levels as compared to controls. The accumulation of damaged proteins negatively correlated with hepatic S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratios. CONCLUSIONS: Ethanol consumption results in the accumulation of modified proteins bearing atypical isoaspartyl residues via impaired in vivo PIMT activity. Betaine administration prevents the ethanol-induced accumulation of isoaspartyl-containing proteins by restoring the PIMT-catalyzed protein repair reaction through normalizing the hepatocellular SAM:SAH ratios. PMID- 17336421 TI - Transport of Escherichia coli through variably saturated sand columns and modeling approaches. AB - A sand column leaching system with well-controlled suction and flow rate was built to investigate the effects on bacterial transport of air-water interface effects (AWI) correlated to water content, particle size, and column length. Adsorption of Escherichia coli strain D to silica sands was measured in batch tests. The average % adsorption for coarse and fine sands was 45.9+/-7.8% and 96.9+/-3.2%, respectively. However, results from static batch adsorption experiments have limited applicability to dynamic bacterial transport in columns. The early breakthrough of E. coli relative to bromide was clear for all columns, namely c. 0.15 to 0.3 pore volume earlier. Column length had no significant effects on the E. coli peak concentration or on total recovery in leachate, indicating retention in the top layer of sands. Tailing of breakthrough curves was more prominent for all fine sand columns than their coarse sand counterparts. Bacterial recovery in leachate from coarse and saturated sand columns was significantly higher than from fine and unsaturated columns. Observed data were fitted by the convection-dispersion model, amended for one-site and two-site adsorption to particles, and for air-water interface (AWI) adsorption. Among all models, the two-site+AWI model achieved consistently high model efficiency for all experiments. Thus it is evident from experimental and modeling results that AWI adsorption plays an important role in E. coli transport in sand columns. PMID- 17336422 TI - Use of tracer tests to investigate changes in flow and transport properties due to bioclogging of porous media. AB - Tracer tests were conducted in three laboratory columns to study changes in the hydraulic properties of a porous medium due to bioclogging. About 30 breakthrough curves (BTCs) for each column were obtained. The BTCs were analyzed using analytical equilibrium and dual-porosity models, and estimates of the hydrodynamic dispersion and mass transfer coefficients were obtained by curve fitting. The change in transport properties developed in three stages: an initial phase (I) with no significant changes in transport properties, phase II with growth of biomass near the inlet of the columns causing changes in dispersivity, and phase III with added growth of micro-colonies deeper in the columns causing mass transfer of solutes from the water phase to the biophase. Tracer transport changed from being uniform to more non-uniform with increase in mass transfer of the tracer between the mobile phase and the immobile biomass. An increase in the bulk dispersivity value of up to one order of magnitude was observed. Numerical simulations suggest that local dispersivity values may be as much as 40 times higher in the more severe clogged areas inside the column. The bulk hydraulic conductivities of the columns decreased by up to three orders of magnitude. The hydraulic conductivity and dispersivity parameters were almost recovered after disinfection of the columns. Different models relating the changes of the hydraulic conductivity to the changes in the mobile porosity due to bioclogging were reviewed, and the micro-colony relation of Thullner et al. [Thullner, M., Zeyer, J., Kinzelbach, W., 2002. Influence of microbial growth on hydraulic properties of pore networks, Transport in Porous Media, 49, 99-122.] was found to best describe the relation between the bulk hydraulic parameters. PMID- 17336424 TI - Understanding gardening and dietary habits among youth garden program participants using the Theory of Planned Behavior. AB - Sedentary lifestyles, along with diets low in fruits, vegetables, and complex carbohydrates, and high in fat and total energy are increasing among youth. These unhealthy behaviors contribute to an increase in childhood overweight, which is associated with type 2 diabetes, hypertension, and heart disease. Healthful dietary behaviors, such as eating a balanced and varied diet may be addressed in garden-based programs for youth. Therefore, this project assessed the influence of a garden program, with a newly developed nutrition curriculum, on youth's eating and gardening behavior using the Theory of Planned Behavior. The model included the constructs of attitude, subjective norm, and perceived behavioral control (PBC). Youth (age 8-15 years) involved in a garden program in Minneapolis/St. Paul, Minnesota completed a pre- (n=96) and a post-survey (n=66) assessing the theory's constructs with regard to eating and gardening behaviors. Fruit and vegetable consumption were assessed using survey questions and a 24-h recall. In addition to finding gender differences regarding associations between intention and behavior and the constructs correlated with behavior, results indicated that attitude was most predictive of intention at both pre- and post survey for both boys and girls with behavior associated to PBC in girls, but not for boys. A high level of intention for boys pre-survey marginally predicted some behavioral change post-survey, but girls with high levels of intention at pre survey did not show positive behavioral changes at post-survey. Additionally, the garden program positively impacted youth fruit and vegetable consumption, as determined from a mean computed from the responses to the fruit and vegetable behavior survey questions and the 24-h recall food group data. Because youth in the garden program consumed more fruit and vegetables at post-survey compared to pre-survey, we conclude that garden programs may be a viable way to assist youth in making healthy lifestyle changes. PMID- 17336423 TI - Assessment of infant feeding styles among low-income African-American mothers: comparing reported and observed behaviors. AB - This study's goal was to provide a detailed description of feeding styles adopted by a sample of African-American women in feeding their infants in North Carolina, and to examine the correspondence between reported and observed feeding styles. Cross-sectional semi-structured interview and videotaped data were gathered in the homes of 20 participating low-income mothers of infants aged 3-20 months. Feeding styles were characterized through a tailored coding scheme (the Infant Feeding Styles Video Coding Scheme, IFSVCS) applied to both interview and video taped data. We found that the most frequent feeding styles identified for both interviews and videotaped observations was restrictive, but that mothers were roughly equally divided among predominantly controlling (pressuring or restrictive) and less controlling (laissez-faire or indulgent) styles across methods. However, for over 2/3 of the sample, there was a lack of correspondence between interview and video-taped feeding styles. This unique characterization and comparison of observed and reported infant feeding styles provides additional insights into parental feeding approaches among mothers of infants at high risk of obesity, and highlights the need for further study of feeding style assessment and potential impact on infant weight outcomes. PMID- 17336425 TI - Manipulation of serotonin signal suppresses early phase of behavioral aging in Caenorhabditis elegans. AB - Aging is associated with progressive changes in behavioral functions, in part caused by muscle frailty, called sarcopenia. However, it was not clear whether certain neurotransmitters are directly involved in behavioral aging. Here we investigated aging of locomotion behaviors with an associative learning property, called basal and enhanced slowing response in Caenorhabditis elegans. Basal slowing response is a modest slowdown in response to food, while enhanced slowing response is a greater slowdown response when animals experience starvation. The behaviors are mediated by dopamine and serotonin, respectively. During aging, basal slowing response was increased, resulting in a diminished difference between the two slowing responses. The behavioral change occurred during early phase of aging prior to the timing when sarcopenia was observed in previous studies. Interestingly, expression of a serotonin biosynthesis marker, tph 1Colon, two colonsGFP, was increased in old animals. Serotonin receptor antagonists and deletion mutants of their target receptor genes (ser-1 and ser-4) partially suppressed age-related changes in locomotion behaviors. Thus, manipulating serotonin signal at receptor levels suppresses early phase of locomotion aging. PMID- 17336426 TI - Polyamidoamine (PAMAM) dendrimers as biocompatible carriers of quinolone antimicrobials: an in vitro study. AB - Quinolones, an expanding class of clinically established potent antibiotics, is not freely soluble in water which prevents the design of liquid dosage forms and restricts their use in topical applications. In the present study we investigated the potential of polyamidoamine (PAMAM) dendrimers as drug carriers of quinolones (nadifloxacin and prulifloxacin) by aqueous solubility and antibacterial activity studies. Results showed that the aqueous solubility of nadifloxacin and prulifloxacin was significantly increased by PAMAM dendrimers. Microbiology studies showed that nadifloxacin and prulifloxacin still exhibit their strong antimicrobial activities in the presence of dendrimers. These studies indicated that PAMAM dendrimers might be considered as biocompatible carriers of quinolones under suitable conditions. PMID- 17336427 TI - Synthesis, identification and antiplatelet evaluation of 2-morpholino substituted benzoxazines. AB - A number of 2-morpholino substituted benzoxazines have been prepared in order to test their effectiveness against ADP and collagen induced platelet aggregation. The reaction of 2-thio-1,3-benzoxazines with morpholine has been generalised to enable the use of substituted benzoxazines. Two separate methods were used to prepare 7-O-2-morpholino substituted benzoxazines from 7-hydroxy-2-morpholino benzoxazines. Antiplatelet testing was carried out on 15 of the title compounds. 7-(2-Chloroethoxy)-8-methyl-2-morpholin-4-yl-4H-1,3-benzoxazin-4-one 15d and 7-[2 (4-methylpiperazin-1-yl)ethoxy]-8-methyl-2-morpholin-4-yl-4H-1,3-benzoxazin-4-one 16d showed potent activity against ADP and collagen induced platelet aggregation. The structures of the newly prepared compounds were confirmed by microanalysis as well as the analysis of IR, (1)H and (13)C NMR. PMID- 17336428 TI - Synthesis and antioxidant activity of new homocarnosine beta-cyclodextrin conjugates. AB - Several in vitro and in vivo studies have suggested that carnosine (beta-alanil-L histidine) and homocarnosine (beta-aminobutyril-L-histidine) can act as scavengers of reactive oxygen species. beta-Cyclodextrin was functionalized with homocarnosine, obtaining the following new bioconjugate isomers: 6(A)-[(4-{[(1S) 1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}-4-oxobutyl)amino]-6(A)-deoxy-beta cyclodextrin and (2(A)S,3(A)R)-3A-[(4-{[(1S)-1-carboxy-2-(1H-imidazol-4 yl)ethyl]amino}-4-oxobutyl)amino]-3(A)-deoxy-beta-cyclodextrin. Pulse radiolysis investigations show that the beta-cyclodextrin homocarnosine bioconjugates are scavengers of (*)OH radicals because of the formation of stable imidazole centered radicals and the scavenger ability of glucose molecules of the macrocycle. The ability of these new beta-cyclodextrin derivatives to inhibit the copper(II) driven LDL oxidation was determined in comparison with that displayed by the analogous carnosine derivatives. Both the beta-cyclodextrin carnosine isomers show a higher protective effect than that of free dipeptide and homocarnosine derivatives, bringing into light the role of the beta-CD cavity. The ability of these new beta-cyclodextrin derivatives to inhibit the copper(II) driven LDL oxidation was determined in comparison with that displayed by the analogous carnosine derivatives. Both the beta-cyclodextrin carnosine isomers show a higher protective effect than that of free dipeptide and homocarnosine derivatives, bringing into light the role of the beta-CD cavity. PMID- 17336429 TI - Syntheses of new tetrasubstituted thiophenes as novel anti-inflammatory agents. AB - A series of new tetrasubstituted thiophenes (4a-4i, 5a-5i and 6a-6f) have been synthesized as novel anti-inflammatory agents and were evaluated for their anti inflammatory activity in carrageenin-induced rat hind paw oedema model at the doses of 10, 20 and 40mg/kg body weight. Among ester series, the best compound 4c showed 71% protection at 10mg/kg, 72% at 20mg/kg, and 76% at 40mg/kg to inflamed paw; while in acid series 5a showed 79% protection at 10mg/kg, 80% at 20mg/kg, and 70% at 40mg/kg, and 5c showed 72% protection at 10mg/kg, 75% at 20mg/kg, and 69% at 40mg/kg, to inflamed paw. In case of oxime series 6a-6f, the anti inflammatory activities of the candidates were found to be poor as compared to acid and ester series. It was found on the basis of SAR studies of target compounds, that the presence of OCH(3) at R(2) position and H, OCH(3) at R(1) are one of the requirements for eliciting comparable anti-inflammatory activity in both tetrasubstituted thiophenes' ester and acid series. Compounds 4a-4i, 5a-5i were investigated for their analgesic activity in acetic acid induced writhing response model at 10mg/kg dose. Among the ester series compound 4e showed maximum protection of 60%, while 4a, 4b, and 4i exhibited 55%, 45%, and 43% protection, respectively. The result showed that presence of H, Cl at R(1) and OCH(3), CH(3) at R(2) in tetrasubstituted thiophene ester series enhances their analgesic activity. The candidates of acid series 5a-5i showed poor analgesic activity as compared to the standard drug ibuprofen. Compounds 4a-4i, 5a-5i were evaluated for their in vitro antioxidant nitric oxide radical scavenging assay. Among the ester series 4a showed maximum in vitro nitric oxide radical scavenging activity having IC(50) value 30.08microg/ml while in acid series 5a has IC(50) value 25.20microg/ml. The results showed that the presence of R(1)=H, R(2)=OCH(3) and R(1)=R(2)=OCH(3) enhances nitric oxide radical scavenging property in tetrasubstituted thiophenes' acid series. PMID- 17336430 TI - Registered nurses' perceptions of educational preparation for professional work and development in their profession. AB - There is a lack of knowledge regarding graduate nurses' experiences of preparation in nursing education for their work in health care. The aim was to describe registered nurses' (RNs) perceptions of preparation in nursing education for their professional work and development in the nursing profession. The sample consisted of 339 RNs with 3 years experience taken from Swedish class registers for graduation in nursing education. A questionnaire was sent by post to 327 RNs. The response rate was 70.3%. The results (n=219) show that the most important domains of knowledge for RNs' work were biological science, medical science and nursing, whereas humanities and social science were less important. The importance of medical science was significantly lesser in community care and nursing in emergency care. Research methodology was of little importance for RNs' work. RNs could not make use of or conduct research in their work but research planning was significantly higher for those with extensive university education. This study mainly indicates that RNs need a stimulating work environment, including mentoring and support to enable continuous professional development in health care. PMID- 17336431 TI - Vaccine adjuvants revisited. AB - The development of new adjuvants for human vaccines has become an expanding field of research in the last thirty years, for generating stronger vaccines capable of inducing protective and long-lasting immunity in humans. Instead of such efforts, with several adjuvant strategies approaching to requirements for their clinical application, limitations like adjuvant toxicity remain to be fully surpassed. Here we summarize the current status of adjuvant development, including regulatory recommendations, adjuvant requirements, and adjuvant categories like mineral salts, tensoactive compounds, microorganism-derived adjuvants, emulsions, cytokines, polysaccharides, nucleic acid-based adjuvants, and a section dedicated to particulate antigen delivery systems. The mechanisms of adjuvanticity are also discussed in the light of recent findings on Toll-like receptors' biology and their involvement on immune activation. PMID- 17336432 TI - Virosome-mediated delivery of tumor antigen to plasmacytoid dendritic cells. AB - Cytotoxic T lymphocytes (CTL) are crucial in viral clearance and tumor growth control. Thus the induction of CTL activity is an important aim in vaccine development. We investigate an innovative delivery system for peptide transfer to the MHC class I processing pathway of APC with the aim to trigger CTL in the context of an antitumoral response. The strategy relies on a novel antigen delivery system termed "chimeric immunopotentiating reconstituted influenza virosomes" (CIRIV) targeting plasmacytoid dendritic cells (PDC). By using virosomes containing encapsulated Melan-A peptide and a PDC line developed in our laboratory, we evaluated the response of Melan-A specific T cells. Virosomes have the capacity to bind PDC and are endocyted within vesicles in the cytosol. This endocytosis is inhibited by neuraminidase, suggesting that it is mediated by sialic acid present on cell surface. Furthermore, PDC loaded with Melan-A virosomes can induce a Melan-A specific T cell activation. Interestingly, they activate T cells with a better efficiency than PDC loaded with a free peptide and when PDC where previously activated by a TLR ligand. These results indicate that virosomes could be a suitable delivery system for tumor peptide in immunotherapy of cancer. PMID- 17336433 TI - Evaluation of the induction of NS3 specific BVDV antibodies using a commercial inactivated BVDV vaccine in immunization and challenge trials. AB - In order to evaluate whether cattle vaccinated with an inactivated vaccine against bovine viral diarrhoea virus (BVDV) can be differentiated serologically from BVDV infected animals, two different aspects were investigated. Firstly the antibody response against non-structural proteins (NS) was measured after multiple vaccinations of cattle with a single or double dose of a commercially available inactivated BVDV vaccine. In a second study, the animals were first vaccinated with the product, and then infected with BVDV. The antibody response was determined in four different commercial ELISA systems. It can be concluded, that the inactivated BVD vaccine exhibits properties of a marker vaccine when an appropriate antibody NS3 ELISA is applied: after vaccination NS3-specific antibody levels are low or undetectable, but the vaccination does in the present study not show any interference with the development of antibodies against NS3 after subsequent field virus infection. PMID- 17336434 TI - Desmoid tumour following a distal radius fracture--a complication or a coincidence? AB - We describe a case of a desmoid tumour occurring 15 months following an uncomplicated fracture of the left distal radius. The occurrence of a desmoid tumour after fracture is extremely rare and a Medline search revealed only two previous reports. The correlation between the site of trauma and the tumour and the time interval between trauma and presentation strongly supports a causal role of the fracture in the occurrence of this tumour. PMID- 17336435 TI - Adopting a population-level approach to parenting and family support interventions. AB - Evidence-based treatments and preventive interventions in the child and family area have not met with widespread adoption by practitioners. Despite the high prevalence of child behavioral and emotional problems, many parents and families in need are not receiving or participating in services, and when they do, the most efficacious interventions are not what is usually provided. Simultaneously addressing the issues of low penetration and insufficient dissemination of evidence-based programming requires a population approach to parenting and family support and intervention. Process issues are important, particularly in relation to engagement of stakeholders, recruitment of practitioners, consideration of organizational factors, and use of media and communication strategies. This article discusses why there is a need for a population-based approach, provides a framework of how to conceptualize such an approach, and describes an example from our own work of a recently initiated prevention trial that illustrates a population-based approach in action. The rationale, structure, and goals of the Triple P System Population Trial are described in the context of the aforementioned population framework. PMID- 17336436 TI - People, other animals and health knowledges: towards a research agenda. AB - By serving as experimental models for human disease, animals have been instrumental to constructing biomedical knowledge. On the other hand, animals themselves increasingly benefit from biomedical expertise and technologies, as patients in their own right. Healthy companion animals have recently come to be viewed explicitly as potential sources of human health, which contrasts with the potential for animals to injure people or transmit infectious disease. In studies of biomedical and other health knowledges, nevertheless, only the animal model role has been explored in any depth. In this review article, we sketch and discuss three research concerns that currently inform studies of biomedical knowledge: medicalization and biomedicalization; constructing biomedical knowledge; and a concern with heterogeneity. We conclude that a more comprehensive and nuanced account of contemporary societies will result from further consideration of the importance of animals for how people understand health. PMID- 17336437 TI - Damage effects of dust storm PM2.5 on DNA in alveolar macrophages and lung cells of rats. AB - The aim of the present study was to investigate in vitro toxicological effects of PM2.5 suspensions, their water-soluble fraction and solvent-extractable organics from dust storm on the viability and DNA of rat alveolar macrophages and in vivo toxicological effects of PM2.5 suspensions on DNA of lung cells of rats. PM2.5 samples from dust storm and normal weather were collected in Baotou city, Inner Mongolia Autonomous Region, and Wuwei city, Gansu Province, China, in March, 2004. DNA damage was detected with single cell gel electrophoresis technique and cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The results showed that: (1) In vitro, PM2.5 suspensions, their water-soluble fraction and solvent-extractable organics from both dust storm and normal weather caused a decrease of the cell viability and an increase of DNA damage of rat alveolar macrophages in a dose-response manner; for both Baotou city and Wuwei city, the samples of normal weather showed higher DNA damage than those of dust storm at the highest treated dosage; for both normal weather PM2.5 and dust storm PM2.5, their solvent-extractable organics showed higher DNA damage than the water-soluble fraction. (2) In vivo, PM2.5 from both dust storm and normal weather caused an increase of DNA damage of rat lung cells in a dose-response manner. (3) Baotou city is one of the heavy industrial cities, while Wuwei is one of agricultural cities in Northwest region of China. The effects induced by normal weather samples in Baotou city slightly higher than those in Wuwei city on DNA damage, though there was no significant difference was found between two cities. These results lead to conclusions that dust storm PM2.5 as well as normal weather PM2.5 could lead to DNA damage and the organic compounds and the insoluble particle-core might be the main contributors to DNA damage. Our results suggest that the risk of health effects may be greater during dust storms because dust storm PM2.5 whose airborne mass were much higher. Further studies are needed to determine the components of dust storm particles that may contribute to the particle toxicity. PMID- 17336438 TI - Evaluation of antioxidant potential of ethyl acetate extract/fractions of Acacia auriculiformis A. Cunn. AB - The present study estimates the free radical scavenging activity of the ethyl acetate extract/fractions of Acacia auriculiformis A. Cunn in different assays viz. 1'-1' diphenyl-2'picrylhydrazyl (DPPH), deoxyribose (site specific and non site specific), relative reducing power, chelating power and lipid peroxidation. The bark powder of the plant was extracted with different solvents by maceration method in the order of increasing and decreasing polarity. The crude ethyl acetate extract was partitioned with ethyl acetate and water (Flow Chart 1 and 2). The scavenging activity of fractions was found to be more as compared to the crude extract. The percent inhibition with water fraction of ethyl acetate extract was observed to be 71.2%, 73.66%, 83.37%, 75.63% and 72.92% in DPPH, chelating power, lipid peroxidation, site specific and non-site specific deoxyribose scavenging assays respectively at maximum concentration tested. l ascorbic acid and BHT were used as reference compounds for comparing the activity of plant extract/fractions. Studies are in progress to evaluate the effect of extract/fractions in other antioxidant assays and identify the factors responsible for the activity. PMID- 17336439 TI - Arsenic in seaweed--forms, concentration and dietary exposure. AB - This study has measured the content of total and inorganic forms of arsenic in seaweed available on retail sale for consumption, to provide data for dietary exposure estimates and to support advice to consumers. A total of 31 samples covering five varieties of seaweed were collected from various retail outlets across London and the internet. All of the samples were purchased as dried product. For four of the five varieties, soaking was advised prior to consumption. The recommended method of preparation for each individual sample was followed, and total and inorganic arsenic were analysed both before and after preparation. The arsenic remaining in the water used for soaking was also measured. Arsenic was detected in all samples with total arsenic at concentrations ranging from 18 to 124 mg/kg. Inorganic arsenic, which can cause liver cancer, was only found in the nine samples of hijiki seaweed that were analysed, at concentrations in the range 67-96 mg/kg. Other types of seaweed were all found to contain less than 0.3mg/kg inorganic arsenic, which was the limit of detection for the method used. Since consumption of hijiki seaweed could significantly increase dietary exposure to inorganic arsenic, the UK Food Standards Agency (FSA) issued advice to consumers to avoid eating it. PMID- 17336440 TI - Evaluating the combinative effects on human lymphocyte DNA damage induced by ultraviolet ray C plus 1.8 GHz microwaves using comet assay in vitro. AB - The objective of this study was to observe whether 1.8 GHz microwaves (MW) (SAR, 3 W/kg) exposure can influence human lymphocyte DNA damage induced by ultraviolet ray C (UVC). The lymphocytes, which were from three young healthy donors, were exposed to 254 nm UVC at the doses of 0.25, 0.5, 0.75, 1.0, 1.5 and 2.0 J m(-2), respectively. The lymphocytes were irradiated by 1.8 GHz MW (SAR, 3 W/kg) for 0, 1.5 and 4 h. The combinative exposure of UVC plus MW was conducted. The treated cells were incubated for 0, 1.5 and 4 h. Finally, comet assay was used to measure DNA damage of above treated lymphocytes. The results indicated that the difference of DNA damage induced between MW group and control group was not significant (P>0.05). The MTLs induced by UVC were 1.71+/-0.09, 2.02+/-0.08, 2.27+/-0.17, 2.27+/-0.06, 2.25+/-0.12, 2.24+/-0.11 microm, respectively, which were significantly higher than that (0.96+/-0.05 microm) of control (P<0.01). MTLs of some sub-groups in combinative exposure groups at 1.5-h incubation were significantly lower that those of corresponding UVC sub-groups (P<0.01 or P<0.05). However, MTLs of some sub-groups in combinative exposure groups at 4-h incubation were significantly higher that those of corresponding UVC sub-groups (P<0.01 or P<0.05). In this experiment it was found that 1.8 GHz (SAR, 3 W/kg) MW exposure for 1.5 and 4 h did not enhance significantly human lymphocyte DNA damage, but could reduce and increase DNA damage of human lymphocytes induced by UVC at 1.5-h and 4-h incubation, respectively. PMID- 17336441 TI - TBP binding capacity of the TATA box is associated with specific structural properties: AFM study of the IL-2R alpha gene promoter. AB - DNA is not only a nucleotide sequence which allows the binding of regulators but its intrinsic structural properties such as curvature and flexibility are also viewed as playing an active role in the regulation of transcription. Our combination of computer modelling and AFM imaging allow direct access to DNA curvature and flexibility. We have searched for these DNA structural features involved in transcription regulation within the IL-2Ralpha gene promoter. Investigation of these structural characteristics shows concordant results. First, in the core promoter, the region containing the functional TATA box shows intrinsic curvature associated with a peculiar distribution of flexibility. Both these inherent properties are characteristic of this region as compared with the other parts of the promoter. Second, the proximal promoter exhibits two important regions: a first one flexible and curved, followed by a segment of rigid linear DNA, each localised within one of the two Positive Regulatory Regions PRRI and PRRII respectively. Based on these observations, we propose different roles for DNA curvature and/or flexibility in promoter sequences. PMID- 17336442 TI - Viral suppression of the interferon system. AB - Type I interferons (IFN-alpha/beta) were originally discovered by their strong and direct antiviral activity [A. Isaacs, J. Lindenmann, Virus interference. I. The interferon, Proc. R. Soc. Lond. B Biol. Sci. 147 (1957) 258-267]. (see review by J. Lindenmann on p. 719, in this issue). Nevertheless, only very recently it was entirely realized that viruses would not succeed without efficient tools to undermine this potent host defense system. Current investigations are revealing an astonishing variety of viral IFN antagonistic strategies targeting virtually all parts of the IFN system, often in a highly specific manner. Viruses were found to interfere with induction of IFN synthesis, IFN-induced signaling events, the antiviral effector proteins, or simply shut off the host cell macromolecule synthesis machinery to avoid booting of the antiviral host defense. Here, we will describe a few well-characterized examples to illustrate the sophisticated and often multi-layered anti-IFN mechanisms employed by viruses. PMID- 17336443 TI - Expression level of heterologous tat genes is crucial for in vivo reconstitution of a functional Tat translocase in Escherichia coli. AB - The Tat system has the remarkable capacity of exporting proteins in folded conformation across the cytoplasmic membrane. The functional Tat translocase from Gram-negative bacteria consists of TatA, TatB and TatC proteins. To gain information about the species specificity of the Tat translocase, we cloned tat genes from Gram-negative pathogens Shigella flexneri 2a str. 301, Vibrio cholerae El Tor N16961, Pseudomonas aeruginosa PAO1, thermophilic Sulfolobus solfataricus P2, Thermus thermophilus HB8 and from three Magnetospirillum species (AMB-1, MS-1 and MSR-1), and assessed the capacity of these Tat systems to restore the Tat dependent growth defect of Escherichia coli tat mutants. We found that whereas the tat genes from the thermophilic bacterial and archaeal species were not functional in E. coli, other tat genes could all complement the phenotype of the E. coli tat mutants. In addition, a chimera composed of the N-terminus of V. cholerae TatE and C-terminus of M. magneticum TatA was functional. Whereas the expression of the tatABC genes from P. aeruginosa and Magnetospirillum strains must be induced to obtain a functional Tat system, overproduction of the V. cholerae TatABC proteins abolished the complementation. The complementation impairment seemed to be correlated with increasing level of slow-migrating TatC isoforms. In vitro studies showed that slow-migrating TatC isoforms in the purified V. cholerae TatABC complex increased with storage time. Together these results showed that the Tat translocases from the Gram-negative bacteria are generally functional in E. coli and the expression level is crucial for in vivo reconstitution of a functional Tat translocase. PMID- 17336444 TI - The effects of camptothecin on RNA polymerase II transcription: roles of DNA topoisomerase I. AB - Eukaryotic DNA topoisomerase I is active in transcribed chromatin domains to modulate transcription-generated DNA torsional tension. Camptothecin and other agents targeting DNA topoisomerase I are used in the treatment of human solid cancers with significant clinical efficacy. Major progress has been achieved in recent years in the understanding of enzyme structures and basic cellular functions of DNA topoisomerase I. Nevertheless, the precise enzyme functions and mechanisms during transcription-related processes remain unclear. The current understanding of the molecular action of camptothecin emphasizes the drug action against the enzyme and the production of irreversible breaks in the cellular DNA. However, the high drug potency is hardly fully explained by the DNA damage outcome only. In the recent past, several unexpected findings have been reported in relation to the role of eukaryotic topoisomerase I during transcription. In particular, the function of DNA topoisomerase I and the molecular effects of its inhibition on transcription-coupled processes constitute a very active research area. Here, we will briefly review relevant investigations on topoisomerase I involvement in different stages of transcription, discussing both enzyme functions and drug effects on molecular processes. PMID- 17336445 TI - Identification and domain mapping of Dictyostelium discoideum type-1 protein phosphatase inhibitor-2. AB - The protein phosphatase type-1 catalytic subunit (PP1c) does not exist freely in the cell and its activity must be very strictly controlled. Several protein inhibitors of PP1c have been described including the classical mammalian inhibitor-1 (I-1) and inhibitor-2 (I-2). Association of these inhibitors with PP1c appears to involve multiple contacts and in the case of I-2 no less than five I-2 interaction subdomains have been proposed. In this report, we provide both in vitro and in vivo evidence that the Dictyostelium discoideum genome encodes a protein (DdI-2) that is an ortholog of mammalian I-2, being the first PP1c interacting protein characterized in this social amoeba. Despite the low overall sequence similarity of DdI-2 with other I-2 sequences and its long N terminal extension, the five PP1c interaction motifs proposed for mammalian I-2 are reasonably conserved in the Dictyostelium ortholog. We demonstrate that DdI-2 interacts with and inhibits D. discoideum PP1c (DdPP1c), which we have previously characterized. Moreover, using yeast two-hybrid assays we show that a stable interaction of DdI-2 with DdPP1c requires multiple contacts. PMID- 17336446 TI - High-precision FLIM-FRET in fixed and living cells reveals heterogeneity in a simple CFP-YFP fusion protein. AB - We have used widefield photon-counting FLIM to study FRET in fixed and living cells using control FRET pairs. We have studied fixed mammalian cells expressing either cyan fluorescent protein (CFP) or a fusion of CFP and yellow fluorescent protein (YFP), and living fungal cells expressing either Cerulean or a Cerulean Venus fusion protein. We have found the fluorescence behaviour to be essentially identical in the mammalian and fungal cells. Importantly, the high-precision FLIM data is able to reproducibly resolve multiple fluorescence decays, thereby revealing new information about the fraction of the protein population that undergoes FRET and reducing error in the measurement of donor-acceptor distances. Our results for this simple control system indicate that the in vivo FLIM-FRET studies of more complex protein-protein interactions would benefit greatly from such quantitative measurements. PMID- 17336447 TI - Immersion frying for the thermal drying of sewage sludge: an economic assessment. AB - This paper presents an economic study of a novel thermal fry-drying technology which transforms sewage sludge and recycled cooking oil (RCO) into a solid fuel. The process is shown to have significant potential advantage in terms of capital costs (by factors of several times) and comparable operating costs. Three potential variants of the process have been simulated and costed in terms of both capital and operating requirements for a commercial scale of operation. The differences are in the energy recovery systems, which include a simple condensation of the evaporated water and two different heat pump configurations. Simple condensation provides the simplest process, but the energy efficiency gain of an open heat pump offset this, making it economically somewhat more attractive. In terms of operating costs, current sludge dryers are dominated by maintenance and energy requirements, while for fry-drying these are comparatively small. Fry-drying running costs are dominated by provision of makeup waste oil. Cost reduction could focus on cheaper waste oil, e.g. from grease trap waste. PMID- 17336448 TI - Editorial comment on: Collecting duct renal cell carcinoma: a matched analysis of 41 cases. PMID- 17336449 TI - Collecting duct renal cell carcinoma: a matched analysis of 41 cases. AB - OBJECTIVES: Collecting duct renal cell carcinoma (CDRCC) is a rare but reportedly aggressive histologic subtype. We assessed the stage and histologic features of patients with CDRCC and compared cancer-specific mortality in CDRCC and matched patients with clear-cell renal cell carcinoma (CRCC). METHODS: Forty-one (0.6%) patients with CDRCC and 5246 CRCC patients were identified within a cohort of 6608 patients treated with either radical or partial nephrectomy for renal cancer. Within the 5246 CRCC cases, 105 were matched with CDRCC cases for grade, tumour size, and T, N, and M stages. Kaplan-Meier and life table analyses addressed RCC-specific survival. RESULTS: Of all CDRCC patients, 76% had pT3 disease at nephrectomy versus 37% for those with CRCC. The predominant Fuhrman grades were III (56%) and IV (22%) in CDRCC versus II (42%) and III (28%) for CRCC. Moreover, 49% of CDRCC patients were pN1-2 versus 8% for CRCC. Of CDRCC patients 19% had distant metastases at nephrectomy versus 14% for CRCC. Finally, 73% of CDRCC patients had either local or systemic symptoms versus 56% for CRCC. After matching, the RCC-specific mortality of CDRCC patients was no different from that for CRCC patients (RR=1.1; p=0.8). One- and 5-yr CDRCC-specific survival rates were 86% and 48%, respectively, versus 86% and 57% for matched CRCC controls. CONCLUSIONS: CDRCC patients present with more advanced stage and with more aggressive disease compared with CRCC patients. After nephrectomy, when CDRCC cases were matched with CRCC, the same cause-specific survival was seen. PMID- 17336450 TI - Editorial comment on: Collecting duct renal cell carcinoma: a matched analysis of 41 cases. PMID- 17336452 TI - Atypical presentation of Streptococcus zooepidemicus bacteraemia and secondary meningitis. PMID- 17336451 TI - Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. AB - The mechanisms underlying androgen receptor (AR)-mediated progression of prostate cancer following androgen ablation have yet to be fully determined. On this basis we screened naturally occurring mutants of human AR for hormone-independent activity using a yeast model system. An initial screen of 43 different mutants revealed that ARs having a Leu701His mutation (AR(L701H)) exhibited hormone independent activation of a lacZ reporter gene. The AR(L701H) mutant bound dihydrotestosterone to a similar extent as did wild type AR, although its ability to be induced by hormone for transactivation was reduced substantially. Subsequent studies focused on the dependence of AR(L701H) on molecular chaperones for folding to the active state. We found that AR(L701H) was highly dependent on Hsp90 for its hormone-independent activation, suggesting that this chaperone functions in AR(L701H) folding. However, the mutant did not respond specifically to increased levels of FKBP52, suggesting that this chaperone functions at the hormone-dependent activation stage in the folding process. Further studies of AR(L701H) in PC3 cells suggested that this mutant is prohibited from hormone independent transactivation in mammalian cells. However, basal expression of a reporter gene by AR(L701H) was not impaired by the presence of 17-allylamino-17 demethoxygeldanamycin as was wild type AR, suggesting differential interactions of these receptors with molecular chaperones in animal cells. PMID- 17336453 TI - The characteristics and mechanisms of phenol biodegradation by Fusarium sp. AB - Fusarium sp. HJ01 can grow using phenol as only carbon resource and has strong ability of phenol degradation. The effect of pH, temperature and sucrose addition on biodegradative capacity of Fusarium sp. HJ01 was examined. The main metabolism pathways and mechanism of phenol degradation by HJ01 strain is described. This strain exhibited both cathecol 1,2-dioxygenase (C12) and cathecol 2,3-dioxygenase (C23) in free cell extracts obtained from cells grown exclusively on phenol or with sucrose added, suggesting that the intermediate cathecol can be oxidized in the catabolic pathway of ortho and meta fission. Mineral salts added in culture have an inhibition on both C12 and C23. These two enzymes can act and retain its catalytic ability over wide ranges of temperature and pH. C12 activity was optimal at pH 6.8 and 40 degrees C, with significant activity observed in the range from pH 3 to pH 8.8, and in the temperature range from 30 to 50 degrees C. In comparison with C12, the activity of C23 was slightly more sensitive to pH, C23 had a higher activity in alkalescence condition from pH 7.4 to pH 10.6 and was more stable at higher temperatures from 30 to 75 degrees C. PMID- 17336454 TI - Electrochemical oxidation of textile wastewater and its reuse. AB - It is attempted in the present investigation to treat organic pollutant present in the textile effluent using an electrochemical treatment technique. Experiments are carried out in a batch electrochemical cell covering wide range in operating conditions. Due to the strong oxidizing potential of the chemicals produced, the effluent COD is reduced substantially in this treatment technique. The influence of effluent initial concentration, pH, supporting electrolyte concentration and the anode material on pollutant degradation has been critically examined. It is further attempted in the present investigation to reuse the treated wastewater for dyeing purpose. Several cycles of dyeing operations have been performed with the treated textile wastewater and the dye uptake and water quality have been critically examined at each cycle of dyeing process. The results indicate that the electrochemical method is a feasible technique for treatment of textile wastewater and electrochemically treated wastewater can be effectively reused for dyeing application. PMID- 17336455 TI - Removal of chromium from electroplating industry effluents by ion exchange resins. AB - Effluent discharged from the chromium electroplating industry contains a large number of metals, including chromium, copper, nickel, zinc, manganese and lead. The ion exchange process is an alternative technique for application in the treatment of industrial wastewater containing heavy metals and indeed it has proven to be very promising in the removal and recovery of valuable species. The main objective of the present work is to evaluate the performance of commercial ion exchange resins for removing chromium trivalent from industrial effluents, and for this purpose two resins were tested: a chelating exchange resin (Diaion CR11) and a weak cationic resin (Amberlite IRC86). In order to evaluate the sorption capacity of the resins some equilibrium experiments were carried out, being the temperature and pH the main variables considered. The chromium solutions employed in the experiments were synthetic solutions and industrial effluents. In addition, a transient test was also performed as an attempt to understand the kinetic behaviour of the process. PMID- 17336456 TI - Spatiotemporal quantification of tumor necrosis factor-alpha and interleukin-10 after crush injury in rat sciatic nerve utilizing immunohistochemistry. AB - The purpose of this study was to investigate quantitatively the longitudinal temporal, spatial changes of the tumor necrosis factor-alpha (TNF) and interleukin-10 (IL-10) immunopositive cells during Wallerian degeneration and the following regeneration after crush injury in rat sciatic nerve using immunohistochemistry and enzyme linked immunosorbent assay (ELISA). The number of TNF-immunopositive cells reached its peak and increased significantly in all the segments distal to the crush site 3 days after injury. On Day 7, TNF immunopositive cells decreased in all the segments distal to the crush site, and a significant decrease was observed 14 days after injury. From Day 21 to Day 56, there were no significant differences in the numbers of TNF-immunopositive cells. The average size of TNF immunopositive cells became significantly larger with degeneration. The number of IL-10-immunopositive cells decreases significantly 1 day after crush injury. IL-10-immunopositive cells increased on Day 3, returning to control levels. Seven days after injury, a significant increase in the number of IL-10-immunopositive cells was observed. There was also no significant difference in the number of IL-10-immunopositive cells beyond Day 14 except for a part of distal segments. The number of IL-10-immunopositive cells showed no significant differences in all the segments on Day 56. The protein levels of IL 10 measured by ELISA were similar to the result of immunohistochemistry. These results suggest that the significant change in IL-10 occurred prior to the significant change in TNF and that IL-10 may be the key to the change in TNF. PMID- 17336457 TI - An investigation of acetylcholine released in skeletal muscle and protein unbound drug released in blood based on the pyridostigmine bromide (pretreatment drug) sustained-release pellets by microdialysis technique in the rabbit model. AB - Pyridostigmine bromide (PB) is a reversible acetylcholinesterase inhibitor that has been used as a pretreatment drug for "Soman" nerve gas poisoning in combat to increase survival. The once-daily PB-sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods in our laboratory, which was followed by zero-order release mechanism. The results showed that the released concentration of acetylcholine (ACh) in skeletal muscle and the released concentration of protein unbound drug in blood were determined by microdialysis technique to have significant differences (P<0.05) among the three dosage forms (IV injection, commercial IR tablets and the PB-SR pellet). The released concentrations of ACh and protein unbound drug for PB-SR pellets were slower than IV injection and commercial IR tablets; this phenomenon indicating that the retention period of drug efficacy in vivo for PB-SR pellet was longer than the others, that is to say, the PB-SR pellets provided with SR effect in vivo as well. We believe that once-daily administered PB-SR pellets would improve limitations of post-exposure antidotes, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in wars or terrorist attacks in the future. PMID- 17336458 TI - Presence of Hypoderma lineatum stage I larvae in the esophagus of cattle slaughtered in Chihuahua, Chih., Mexico. AB - In order to detect the presence of Hypoderma lineatum stage I larvae within the esophagus of cattle slaughtered in Chihuahua, Chihuahua, Mexico, a total of five samplings were carried out between July and November 2000. In each instance, a random sample was taken from 10% of the animals slaughtered in a single work shift in each of the two slaughterhouses included in this study. The esophagus were cut longitudinally in order to carry out visual inspection and detect the presence of H. lineatum stage I larvae in the submucosa. The larvae were separated and counted. We identified the presence of H. lineatum stage I larvae in the esophagus for all sampling dates, nevertheless, within the last sampling only one esophagus had them. For all sampling dates the prevalence ranged between 11 and 33%; the latter corresponded to the sampling in October. A total of 287 esophagus was inspected of which 54 were positive with one or more larvae (19%); 233 larvae were obtained from these cases. The number of larvae recovered per sampling ranged from 46 to 74 between July and October, the highest number was found in September's sampling. The largest amount of stage I larvae per esophagus was 22 in the months of July and August. Larvae were always located in the submucosa of the esophagus and all were oriented longitudinally. PMID- 17336459 TI - Individual administration of three tanniferous forage plants to lambs artificially infected with Haemonchus contortus and Cooperia curticei. AB - We investigated direct anthelmintic effects associated with the feeding of fresh tanniferous forages against established populations of Haemonchus contortus and Cooperia curticei in lambs. Twenty-four parasite naive lambs were inoculated with a single dose of infective larvae of these two parasites 27 days prior to the start of the feeding experiment. Lambs were individually fed with either chicory (Cichorium intybus), birdsfoot trefoil (Lotus corniculatus), sainfoin (Onobrychis viciifolia) or a ryegrass/lucerne mixture (control) for 17 days. Animals where then united to one flock and subjected to control feeding for another 11 days to test the sustainability of potentially lowered egg excretion generated by tanniferous forage feeding. When compared to the control, administration of all tanniferous forages was associated with significant reductions of total daily faecal egg output specific to H. contortus (chicory: 89%; birdsfoot trefoil: 63%; sainfoin: 63%; all tests P<0.05) and a tendency of reduced H. contortus worm burden (chicory: 15%; birdsfoot trefoil: 49% and sainfoin: 35% reduction). Irrespective of the condensed tannin (CT) containing fodder, no anthelmintic effects were found against C. curticei. Cessation of CT-feeding followed by non CT control feeding did not result in a re-emergence of faecal egg counts based on faecal dry matter (FECDM) in any group, suggesting that egg output reductions are sustainable. The moderate to high concentrations of CTs in birdsfoot trefoil (15.2 g CTs kg(-1) dry matter (DM)) and sainfoin (26.1 g CTs kg(-1) DM) were compatible with the hypothesis that the antiparasitic effect of these forages is caused by their content of CTs. For chicory (3 g CTs kg(-1) DM), however, other secondary metabolites need to be considered. Overall, birdsfoot trefoil and in particular sainfoin seem promising candidates in contributing to an integrated control strategy against H. contortus not only by mitigating parasite related health disturbances of the host but also by a sustained reduction of pasture contamination. PMID- 17336460 TI - The non-algorithmic nature of the hand burn contractures. PMID- 17336461 TI - Free radical reactions might contribute to severe alpha amanitin hepatotoxicity- a hypothesis. AB - Alpha amanitin is a powerful natural hepatotoxin that belongs to the amatoxins isolated from deadly poisonous Amanita phalloides mushroom. The basic molecular mechanism of their toxicity was attributed to inhibition of RNA polymerase II of the eukaryotic cells. At present, the most effective clinical antidote to acute Amanita phalloides mushroom poisoning is silybin, an antioxidant possessing free radical scavenger activity and inhibiting lipid peroxidation, stabilizing membrane structure and protecting enzymes under conditions of oxidative stress. Bearing in mind the biological mechanism of silybin action and the fact that for different amatoxins (alpha, beta, and est. amanitins) does not established straight correlation between their in vivo LD50 and inhibitory constants (Ki) toward RNA polymerase III in vitro determined we supposed some additional toxic effects of these toxins might contribute to their severe hepatotoxicity. Our formerly in vitro experiments demonstrated that alpha amanitin could act either as an antioxidant or as a prooxidant depending on the treatment conditions and toxin concentration. By UV-visible spectroscopy we also shown that alpha amanitin was sensitive to oxidation by a system of lactoperoxidase/H(2)O(2) and assumed formation of free radical toxin intermediates. Having in mind some exogenic compounds including natural toxins can induce increased production of reactive oxygen species (ROS) we suggested similar generation of ROS provoked by alpha amanitin. Our recently in vitro studies have demonstrated that the alpha amanitin could increase superoxide dismutase (SOD) activity and inhibit catalase (CAT) activity to a considerable degree after together incubation of the toxin with any of enzymes. We have also shown that in vitro increased SOD activity was due to superoxide anion radical scavenging activity (SSA) of the toxin. This therefore informed the decision to study the in vivo effect of alpha amanitin on SOD and CAT activity and the level of lipid peroxidation (LPO) products in liver homogenates isolated from mice treated with the toxin. Statistical significant increased level of LPO products was found at the 6th day comparing to the 20th hour after mice treatment with a subletal dose of the toxin. Based on our previous in vitro and present in vivo studies we have made a hypothesize that in vivo during liver accumulation of the toxin it might be transformed to free radical intermediates causing increase in ROS levels. As a result a peroxidative process in hepatocytes might contribute to the severe alpha amanitin hepatotoxicity. PMID- 17336462 TI - Ghrelin may attenuate proinflammatory cytokine-mediated neuropathic pain. AB - Nerve damage that affects peripheral or central nerve systems leads to abnormal pain states referred to as neuropathic pain. The precise mechanisms in neuropathic pain are very complex, since they are thought to originate through multiple pathophysiological processes. There is quite evidence implicating the proinflammatory cytokines in the induction and facilitation of neuropathic pain. This pain syndrome is usually poorly controlled by available medications. Ghrelin, a peptide hormone predominantly secreted from the stomach, is an endogenous ligand to the growth hormone secretagogue receptor. Previous studies showed that ghrelin has potent anti-inflammatory effect; inhibiting proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). Furthermore, there are recent studies which prove the interaction between ghrelin and the systems that play role in pain modulation. Therefore, we hypothesize that ghrelin might ameliorate neuropathic pain by diminishing the proinflammatory cytokines and also regulating pain system. PMID- 17336463 TI - Stem cells adaptive network: mechanism and implications for evolution and disease development. AB - During development, different cells and tissues acquire different programmes of gene expression, so that cells are related to each other through a somatic cells tree or cluster and adult pluripotential stem cells (PSC) may be defined as progenitors that we distinguish in four types according to their biological behaviour. This clustering may segregate specific pathways establishing spatial patterns of cell-cell communications. Thus, we suggest that normal somatic cells renewal is tributary of multipotential stem cells (MSC), while renewal of cells undergoing stress or abnormal death is tributary of PSC through specific pathway(s) from cluster, thus, defining the cell repertoire that will be produced. We also assume that PSC play a pivotal role in evolutionary and propose the theory of "internal clusters competition". According to the functional duality of stem cells (SC) we define a stem cells adaptive network (SCAN) which we believe is linked to the central clock and display two pathways. The diurnal pathway includes SC-somatic cells communications, while the nocturnal pathway includes inter-SC network. These alternate pathways could be activated or repressed as a consequence of change in the biological chirality. This new approach of SC may contribute to our understanding on how some diseases may develop including cancer which could be linked to "cluster illness", while demyelinating and systemic diseases could be related to "PSC locus illness" or "focalised SCAN disturbances" and it explains how any environment stress may act on organism evolution. PMID- 17336464 TI - Radiation therapy, cardiac risk factors, and cardiac toxicity in early-stage breast cancer patients. AB - PURPOSE: The benefits of adjuvant radiation therapy (RT) for breast cancer may be counterbalanced by the risk of cardiac toxicity. We studied the cardiac effects of RT and the impact of pre-existing cardiac risk factors (CRFs) in a population based sample of older patients with breast cancer. METHODS AND MATERIALS: In the Surveillance, Epidemiology and End-Results (SEER)-Medicare database of women > or = 65 years diagnosed with Stages I to III breast cancer from January 1, 1992 to December 31, 2000, we used multivariable logistic regression to model the associations of demographic and clinical variables with postmastectomy and postlumpectomy RT. Using Cox proportional hazards regression, we then modeled the association between treatment and myocardial infarction (MI) and ischemia in the 10 or more years after diagnosis, taking the predictors of treatment into account. RESULTS: Among 48,353 women with breast cancer; 19,897 (42%) were treated with lumpectomy and 26,534 (55%) with mastectomy; the remainder had unknown surgery type (3%). Receipt of RT was associated with later year of diagnosis, younger age, fewer comorbidities, nonrural residence, and chemotherapy. Postlumpectomy RT was also associated with white ethnicity and no prior history of heart disease (HD). The RT did not increase the risk of MI. Presence of MI was associated with age, African American ethnicity, advanced stage, nonrural residence, more than one comorbid condition, a hormone receptor negative tumor, CRFs and HD. Among patients who received RT, tumor laterality was not associated with MI outcome. The effect of RT on the heart was not influenced by HD or CRFs. CONCLUSION: It appears unlikely that RT would increase the risk of MI in elderly women with breast cancer, regardless of type of surgery, tumor laterality, or history of CRFs or HD, for at least 10 years. PMID- 17336465 TI - Practice patterns of radiotherapy in cervical cancer among member groups of the Gynecologic Cancer Intergroup (GCIG). AB - PURPOSE: The aim of this study was to describe radiotherapeutic practice of the treatment of cervical cancer in member groups of the Gynecologic Cancer Intergroup (GCIG). METHODS AND MATERIALS: A survey was developed and distributed to the members of the GCIG focusing on details of radiotherapy practice. Different scenarios were queried including advanced cervical cancer, postoperative patients, and para-aortic-positive lymph node cases. Items focused on indications for radiation therapy, radiation fields, dose, use of chemotherapy, brachytherapy and others. The cooperative groups from North America were compared with the other groups to evaluate potential differences in radiotherapy doses. RESULTS: A total of 39 surveys were returned from 13 different cooperative groups. For the treatment of advanced cervical cancer, external beam pelvic doses and total doses to point A were 47 + 3.5 Gy (mean + SD) and 79.1 + 7.9 Gy, respectively. Point A doses were not different between the North American cooperative groups compared with the others (p = 0.103). All groups used concomitant chemotherapy, with 30 of 36 respondents using weekly cisplatin. Of 33 respondents, 31 intervened for a low hemoglobin level. For a para-aortic field, the upper border was most commonly (15 of 24) at the T12-L1 interspace. Maintenance chemotherapy (after radiotherapy) was not performed by 68% of respondents. For vaginal brachytherapy after hysterectomy, 23 groups performed HDR brachytherapy and four groups used LDR brachytherapy. In the use of brachytherapy, there was no uniformity in dose prescription. CONCLUSIONS: Radiotherapy practices among member groups of the GCIG are similar in terms of both doses and use of chemotherapy. PMID- 17336466 TI - Antifungal activity of Aloe vera leaves. AB - Aloe vera fresh leaves hydroalcoholic plant extract was tested against the mycelial growth of Botrytis gladiolorum, Fusarium oxysporum f.sp. gladioli, Heterosporium pruneti and Penicillium gladioli on Czapek-agar medium. The minimum fungicidal concentration (MFC) varied between 80 and 100 microl/ml, depending on the fungal species. PMID- 17336467 TI - Cloning and characterization of Xenopus laevis Smac/DIABLO. AB - Mitochondria-mediated apoptosis plays a central role in animal development and tissue homeostasis, and mitochondria contain several pro-apoptotic proteins that have key roles in apoptosis. Smac/DIABLO was identified as a mitochondrial protein that is released into the cytosol following apoptotic stimuli, subsequently blocking the anti-apoptotic activity of inhibitor of apoptosis proteins. Through expressed sequence tag (EST) analysis we detected evidence for the presence of a number of Xenopus counterparts to mammalian mitochondrial pro apoptotic proteins. EST and genome sequencing provides evidence for the presence of endonuclease G, AIF, HtrA/Omi and Smac/DIABLO in Xenopus laevis and tropicalis. Here we report the cloning and characterization of X. laevis Smac/DIABLO (XSmac/DIABLO). In this study degenerate primers based on conserved regions of human, mouse and an EST predicted Smac from X. tropicalis were used to amplify cDNA templates from X. laevis. The full length cDNA of Xenopus Smac contained a complete open reading frame of 732 bp, encoding 244 amino acids, that when expressed is observed to be approximately 27 kDa in size. The protein sequence is 49% identical and 71% similar to human Smac, and includes the motifs involved in mitochondrial targeting, and IAP-binding (AIPV). Smac expression was detected throughout early development with multiple transcripts being detected by Northern blot analysis, suggesting the presence of alternatively spliced isoforms. Exogenous expression of Xenopus Smac enhances gamma-irradiation-induced apoptosis in HeLa cells, demonstrating its functional equivalence with mammalian forms. Our study has identified the third vertebrate homologue of Smac/DIABLO, with its structural and functional similarities to mammalian Smac/DIABLO further illustrating the evolutionary conservation of apoptotic pathways across vertebrate species. PMID- 17336468 TI - In vitro competitive adhesion and production of antagonistic compounds by lactic acid bacteria against fish pathogens. AB - The present study describes the screening of five lactic acid bacteria (LAB) for use as probiotics based on their competitive adhesion and production of antagonistic substances against some fish pathogens. A reduction of adhesion of all pathogenic strains tested was obtained with three of the LAB strains (Lactococcus lactis subsp. lactis CLFP100, Lactococcus lactis subsp. cremoris CLFP102 and Lactobacillus curvatus CLFP150). With the exception of fish pathogens Flavobacterium psychrophilum and Renibacterium salmoninarum that were not inhibited by LAB strains, production of antagonistic compounds by all tested LAB was observed against at least one of the indicator strains. Based on mucus adhesion, competitive exclusion, and suppression of fish pathogen growth, the selected LAB strains can be considered for future challenge experiments in fish as a very promising alternative to the use of chemotherapeutic agents. PMID- 17336469 TI - Isolation and characterization of a haemolysin from Trichophyton mentagrophytes. AB - Haemolytic activities of Trichophyton (T.) mentagrophytes were detected and characterized by qualitative and quantitative assays. On Columbia agar supplemented with blood from horses, cattle or sheep, T. mentagrophytes expressed a strong zone of complete haemolysis. No haemolytic activities could be detected in the closely related T. verrucosum var. ochraceum. The same results were obtained after cultivation of the fungi on sterile cellulose acetate filters placed on the surface on Columbia blood agar. After removal of the filter, complete haemolysis was detected below the colony of T. mentagrophytes. A soluble haemolysin from culture supernatant of this strain was isolated and partially purified. Specific haemolytic activity per mg protein was enriched 2.6-fold in filtrate F(1), a fraction obtained as filtrate after filtration through 3kDa cut off membranes. The partially purified haemolysin was neither affected by proteinase K treatment, nor by high and low temperatures, suggesting that it represents a small peptide haemolysin. Accordingly, in a commercial enzymatic activity test only the crude culture filtrate, but none of the subsequent purification fractions showed reactivity. Evaluation of the specificity of the haemolysin using erythrocytes from different mammalian species revealed that sensitivity was highest to those of equines, followed by erythrocytes from sheep, cattle, swine, dogs and humans. None of the erythrocytes was lysed by filtrate F(1) from T. verrucosum var. ochraceum. Furthermore, different eukaryotic cell lines from different species were tested in their sensitivity to cytolytic activities of the haemolysin, but no membrane damage could be detected. PMID- 17336470 TI - Rapid detection of Escherichia coli virulence factor genes using multiplex real time TaqMan PCR assays. AB - Three multiplex real-time TaqMan PCR assays were developed for the detection of Escherichia coli virulence factor genes in veterinary samples. Target virulence factors chosen were the fimbriae K88 (F4), K99 (F5), F41, F17, F18 and 987p (F6) and the toxins LT, STa and CDT IV. Detection of genes coding GAD were included in each assay as an internal control. These assays allow rapid identification of virulence factor genes using identical cycling conditions on an Mx3000Ptrade mark real-time PCR machine with the capacity to test up to 20 strains for 9 virulence genes in 1h. PMID- 17336471 TI - Cadmium-induced renal dysfunction and mortality in two cohorts: disappearance of the association in a generation born later. AB - The association between exposure to environmental cadmium and mortality was investigated in two cohorts. The study population consisted of 275 (cohort I) and 329 (cohort II) residents (aged >or=40 years) in a cadmium-polluted area, Nagasaki Prefecture, Japan, who had participated in health surveys conducted in 1982 and 1992, respectively. The follow-up period extended from 1982 or 1992 to 2005. In the study area, the dietary cadmium intake had decreased after 1980-1983 because of the restoration of cadmium-polluted paddy fields. In cohort I, the mortality rate among those with urinary beta2-microglobulin (beta2-MG) concentration >or=1000 microg/g creatinine (cr.) was 1.41 times higher than the regional reference rate (95% confidence interval [CI] 1.07-1.83). After adjusting for age and other variables, in men, urinary N-acetyl-beta-D-glucosaminidase, and in women, serum creatinine, beta2-MG clearance, and urinary beta2-MG were significantly associated with increased mortality. However, in cohort II, urinary beta2-MG or total protein was not significantly associated with survival. These findings indicate that cadmium-induced renal dysfunction was a significant predictor of mortality, but that such an association is disappearing, probably because of the selective loss of advanced cases and reduced exposure and body burden. PMID- 17336472 TI - Cryopreservation of epididymal bovine spermatozoa from dead animals and its uses in vitro embryo production. AB - The present study aimed to evaluate viability and in vitro fertilizing ability of cryopreserved epididymal spermatozoa obtained from dead animals. To collect spermatozoa, epididymides from three males (Bulls A1, A2 and A3) were collected at a local slaughterhouse. As a reference ejaculate from a bull with known in vitro fertility, was used. Sperm characteristics (motility, chromatin and acrosome integrity) were evaluated before and after cryopreservation. Then, frozen spermatozoa from all animals were used for in vitro fertilization. Cleavage and blastocyst rates at 48 h (day 2) and 168 h (day 7) post in vitro insemination, for bull A1 (82.1 and 38.6%) and A2 (80.7 and 33.8%) were similar (P>0.05) to the reference bull (88.9 and 57.2%). Bull A3 had the lesser cleavage (42.0%) and blastocyst (26.1%) rates. The results showed that epididymal spermatozoa from dead animals can be successfully cryopreserved and used in vitro production of embryos. PMID- 17336473 TI - A pilot study of a Hatha yoga treatment for menopausal symptoms. AB - OBJECTIVE: To assess the feasibility and efficacy of a yoga treatment for menopausal symptoms. Both physiologic and self-reported measures of hot flashes were included. METHODS: A prospective within-group pilot study was conducted. Participants were 12 peri- and post-menopausal women experiencing at least 4 menopausal hot flashes per day, at least 4 days per week. Assessments were administered before and after completion of a 10-week yoga program. Pre- and post treatment measures included: Severity of questionnaire-rated menopausal symptoms (Wiklund Symptom Check List), frequency, duration, and severity of hot flashes (24-h ambulatory skin-conductance monitoring; hot-flash diary), interference of hot flashes with daily life (Hot Flash Related Daily Interference Scale), and subjective sleep quality (Pittsburgh Sleep Quality Index). Yoga classes included breathing techniques, postures, and relaxation poses designed specifically for menopausal symptoms. Participants were asked to practice at home 15 min each day in addition to weekly classes. RESULTS: Eleven women completed the study and attended a mean of 7.45 (S.D. 1.63) classes. Significant pre- to post-treatment improvements were found for severity of questionnaire-rated total menopausal symptoms, hot-flash daily interference; and sleep efficiency, disturbances, and quality. Neither 24-h monitoring nor accompanying diaries yielded significant changes in hot flashes. CONCLUSIONS: The yoga treatment and study procedures were feasible for midlife women. Improvement in symptom perceptions and well being warrant further study of yoga for menopausal symptoms, with a larger number of women and including a control group. PMID- 17336474 TI - 5-Fluorouracil plasma levels and biodegradation of subcutaneously injected drug loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(D,L lactide-co-glycolide) polymers. AB - Microspheres (MS) of 5-fluorouracil-loaded poly(D,L-lactide) (PLA), poly(D,L lactide-co-glycolide) 75/25 (PLGA 75/25) and poly(D,L-lactide-co-glycolide) 50/50 (PLGA 50/50) prepared by the spray-drying technique were subcutaneously injected in the back of Wistar rats in order to evaluate the 5-fluorouracil (5-FU) release and the biodegradation characteristics. Determination of plasma 5-FU concentration by HPLC with analysis of data using a non-compartmental model showed drug in plasma between 9 and 14 days after administration of drug-loaded PLGA 50/50 or PLA and PLGA 75/25 microspheres, respectively, with a maximum drug concentration of 2.4+/-0.2microg/mL at 24h (5-FU-loaded PLGA 50/50 MS), 2.5+/ 0.1microg/mL at 48h (5-FU-loaded PLGA 75/25 MS), and 2.3+/-0.1microg/mL at 24h (5 FU-loaded PLA MS). Pharmacokinetically, a significant increase of AUC (up to 50 times) and MRT (up to 196 times) of 5-FU with regard to the administration of the drug in solution was observed. Scanning electron microscopy and histological studies indicated that a small fibrous capsule was observed around the microspheres in the site of injection. One month after the injection of PLGA 50/50 MS and 2 months after the injection of PLGA 75/25 and PLA MS, masses of polymers, instead of single microspheres, were observed. Close to them, macrophagic cells were present, and blood vessels were observed in the connective tissue. Total absence of fibrous capsule and injected microspheres was observed after 2 (for PLGA 50/50 MS) or 3 (PLGA 75/25 and PLA MS) months. PMID- 17336475 TI - Finnish mitochondrial DNA HVS-I and HVS-II population data. AB - We have analyzed the two hypervariable regions HVS-I and HVS-II of 200 Finnish male individuals for forensic purposes. The distribution of the haplotypes within Finland was determined by the geographical knowledge of the donors' maternal ancestors. In our population sample, we identified 135 different mtDNA haplotypes. Different mtDNA sequences were further divided to haplogroups using the EMPOP software. The most common haplogroups were H (40.0%) and U (27.5%). Subgroup U5b, which contains earlier described "Saami motif", consisted majority (65.5%) of the sample in the U haplogroup. Analysis of the mtDNA sequence hypervariable regions I and II showed that the mtDNA diversity within the Finnish population sample was comparable to other European populations and uniformly distributed. This is contrary to the Y-STR "minimal haplotype" diversity, which in Finland is lower than in any of the other European populations studied so far. PMID- 17336476 TI - Bickerstaff's brainstem encephalitis: a case report. AB - Bickerstaff's brainstem encephalitis (BBE) is a rare diagnosis different from meningoencephalitis with ophthalmoplegia, ataxia and confusion. Less than 100 cases have been described in the literature. We described the fatal case of a 69 year-old man who presented a severe consciousness disorders, distal weakness in the four limbs, and the BBE triad a few days after his admission for pneumonia. PMID- 17336477 TI - Small bowel ultrasound in patients with celiac disease. Retrospective study. AB - OBJECTIVE: Celiac disease (CD) is a common, lifelong disease with small bowel malabsorption based on genetically conditioned gluten intolerance. The clinical manifestation could be very heterogeneous. The proof of celiac disease is now based mainly on clinical and laboratory (antibodies and enterobiopsy) signs, which are in some cases problematic and inconvenient. MATERIALS AND METHODS: In our study we have examined 250 patients with suspection or with proven celiac disease and we evaluated specific ultrasound small bowel changes in this group. In the next step, we chose 59 patients with laboratory proved celiac disease and we statistically compared ultrasound, other laboratory and clinical findings in different forms and stages of the disease. RESULTS: Specific small bowel pathologies in patients with celiac disease (like changes of intestinal villi in different parts of small bowel, abnormal peristalsis and mesenterial lymphadenopathy) can be well visualized by ultrasound and in combination with clinical and laboratory signs ultrasound examination could have an important role in screening, determination of diagnosis and monitoring of patients with different forms of celiac disease. PMID- 17336478 TI - Temporal change of composition and potential activity of the thermophilic archaeal community during the composting of organic material. AB - To date, composting has been regarded as an aerobic process but it has been shown that composting piles are often sources of atmospheric methane. In order to gain a more comprehensive view on the diversity of methanogenic Archaea in compost, gas chromatographical methods and molecular cloning were used to study relationships of thermophilic archaeal communities and changes in methane production potential during compost maturation. According to the thermophilic methane production potential, wide differences could be detected between differently aged compost materials. In material derived from 3- and 4-week-old piles, low and no thermophilic methane production potential, respectively, was observed at 50 degrees C. Material from a 6-week-old pile showed the maximum methane production. With compost maturation, the production slowly decreased again with 6 weeks, 8 weeks, and mature compost showing an optimum methane production potential at 60 degrees C. At 70 degrees C, only 6-week-old material showed a comparable high production of methane. The 16S rRNA-based phylogenetic surveys revealed an increase of archaeal diversity with compost maturation. In the 6-week-old material, 86% of the sequences in the archaeal 16S rRNA library had the highest sequence similarities to Methanothermobacter spp. and the remaining 14% of the clones were related to Methanosarcina thermophila. Quantification of methanogens in 6-week-old material, on the basis of the methane production rate, resulted in values of about 2x10(7) cells per gram fresh weight. In 8-week-old and mature compost material, the proportion of sequences similar to Methanothermobacter spp. decreased to 34% and 0%, respectively. The mature compost material showed the highest variation in identified sequences, although 33% could be assigned to as yet uncultured Archaea (e.g. Rice cluster I, III, and IV). Our results indicate that compost harbours a diverse community of thermophilic methanogens, with changing composition during the maturation process, presumably due to altered pile conditions. Likewise, compost may act as a potential carrier for thermophilic methanogens in temperate soils because it is widely used as a soil amendment. PMID- 17336479 TI - Immunogenicity of therapeutic proteins. Part 1: impact of product handling. AB - The patents of first-generation biopharmaceutical proteins are expiring, creating opportunities for biosimilar products. Unlike conventional generic pharmaceuticals, the development of biosimilar products is far more complex and requires more than a simple demonstration of pharmacological bioequivalence to establish efficacy and safety. The main concern with biosimilar products, as for any therapeutic protein, is immunogenicity and with it the potential for serious clinical sequelae. In the absence of adequate predictors of immunogenicity outside the clinical trial setting, biosimilar products should be evaluated in the same way that any novel pharmaceutical is evaluated. Herein, the factors involved in breaking host tolerance following administration of a therapeutic protein are discussed. The impact of product handling on immunogenicity is considered in the context of some hard-fought lessons that have helped to shape the current era of biopharmaceutical manufacturing, packaging, distribution, storage, and quality assurance. PMID- 17336480 TI - Could office endometrial biopsy be accurate as EBHR for assessing the preoperative tumor grade? PMID- 17336481 TI - The results of a structured diagnostic pathway designed to minimise the chance of breast cancer misdiagnosis. AB - AIM: To describe results from a structured clinic pathway designed to minimise inaccuracies and diagnostic delays in the diagnosis of breast cancer. METHODS: Patients referred to our breast clinic undergo clinical, imaging and biopsy assessment according to a standard protocol. Over 4 years, patients who were discharged with a benign diagnosis and later found to have breast cancer were reviewed. RESULTS: A total of 4366 new referrals were seen in the symptomatic breast clinic and 571 (13%) new cancers were diagnosed. Fourteen of the new cancer patients had been seen in the clinic previously (range 7-48 months) and discharged with a benign diagnosis. None of these tumours appeared to result from misdiagnosis of a lesion previously assessed to be benign. The rate of development of cancer in the cohort discharged with a benign diagnosis was closely similar to that in the normal United Kingdom population. CONCLUSIONS: A structured breast clinic pathway can produce a rate of diagnostic accuracy closely approaching 100%. PMID- 17336482 TI - Tumor regression in mesorectal lymphnodes after neoadjuvant chemoradiation for rectal cancer. AB - AIMS: The histological modification produced by neoadjuvant chemoradiation on primary rectal cancer has been investigated by many authors, and a prognostic value of tumor regression grade (TRG) has been identified. Tumor regression grade on metastatic mesorectal lymphnodes has been never evaluated. The purpose of this study is to analyse the TRG on mesorectal lymphnodes (lymphnode regression grade, LRG) after preoperative chemoradiation in rectal cancer patients and to determine the correlation with TRG of primary tumor. METHODS: Surgical specimens from 35 patients who underwent chemoradiation were included. LRG on mesorectal lymphnodes was assessed by immunohistochemistry. Response to treatment was evaluated by a 5 point LRG based on the ratio of residual tumor to fibrosis. RESULTS: Complete pathologic response (LRG 1) was observed in 18 patients (51%). In 4 patients (11%) no regression was observed (LRG 5). In 4 cases only reactive lymphnodes were found. LRG on lymphnodes significantly correlated with TRG on primary tumor (p<0.05). CONCLUSIONS: Neoadjuvant chemoradiation determines a tumor regression on mesorectal lymphnodes as on primary tumor; further studies are needed to evaluate the prognostic value of LRG. PMID- 17336483 TI - Management of labor pain with single dose spinal analgesia: Indonesian perspective. PMID- 17336484 TI - [The tako-tsubo syndrome: therapeutic stakes]. AB - The authors report the case of 2-old-caucasian women in the pre- and interhospital setting, who presented chest pain with ST segment elevation. Coronary angiography did not show any significant coronary lesion, ventriculography revealed typical aspect of tako-tsubo. It resolved in a short time, with normalisation of the left ventricule function. The tako-tsubo syndrome, or transient left ventricular apical ballooning syndrome, first described by Japanese physicians, is more and more frequently observed in caucasian patients. This cardiomyopathy associates an apical transient dysfunction without any significant coronary lesion. This syndrome is usually observed in elderly women, occurs frequently after acute emotional or physical stress. The clinical presentation looks like an acute coronary syndrome, with chest pain, electrocardiographic changes and moderate cardiac enzymes release. Coronary angiography shows no significant coronary disease and ventriculography a systolic dysfunction with akinesia of middle and apical segments, leading apical ballooning, and basale hyperkinesia. These abnormalities are transient, with quick favorable outcome. The aetiopathegenia is still uncertain. The differential diagnosis with an acute coronary syndrome with thrombosis is not yet possible. Clinical or biological criteria allowing early diagnosis would lead to optimize the therapeutic management. PMID- 17336485 TI - [Does air pollution influence EMS interventions for respiratory causes?]. PMID- 17336487 TI - [Central venous catheterism and cardiac tamponade: comment]. PMID- 17336486 TI - [Critical analysis of noninflammatory treatments of sepsis: lessons learned from previous trials]. AB - A large number of immunomodulatory therapies has been evaluated in patients with severe sepsis and septic shock. Until recently, none of these treatments has ever demonstrated any benefit in terms of decreased mortality. Many biases could interfere with the results of these clinical trials linked to poor comprehension of immune response, pharmacological errors, selection bias, and mistakes in the evaluation of the patients and in the interpretation of the results. Based on these methodological flaws, the authors try to define directions for future clinical trials. PMID- 17336488 TI - [The death certificate: how to draft and why?]. AB - The death certificate must be established within 24 hours following the death and handed to the mayor. The obligation to place in the coffin immediately is planned by a defined list of contagious diseases. Medicolegal obstacle must be ticked if there is a doubt on the cause of death. In order to look into the causes of the death, swabs can be asked by the physician. It is a medical or scientific autopsy to look into the causes of the death apart from a juridical procedure. The presence of a battery prosthesis (pacemaker) must be specified, so that it can be removed by a physician or a thanatopractionner before the placing in the coffin. Death certificate is passed on by the city hall to Insee, which updates the identification national register of physical people. Inserm receives anonymous data of the causes of death allowing to establish the mortality national statistics. In the absence of medicolegal obstacle or obligation to place in the coffin immediately, funeral operations can begin: preservation care, body transport, placing in the coffin and finally burial or cremation. PMID- 17336490 TI - [Anaesthesia for craniosynostosis: differentiate intraoperative hydroelectrolytic management and volume replacement]. PMID- 17336489 TI - [Influence of the analgesic strategy on the respiratory function after thoracic surgery for lobectomy]. AB - OBJECTIVE: To compare the influence of thoracic epidural analgesia (TEA) with intravenous patient-controlled analgesia with morphine (PCA) on the early postoperative respiratory function after lobectomy. STUDY DESIGN: Prospective and comparative observational study. PATIENTS AND METHODS: Fourty-four patients scheduled for lobectomy (n=22 per group) were studied on the evolution of the postoperative respiratory function assessed by the forced vital capacity (FVC) and the forced expired volume (FEV(1)) during the first two postoperative days and the analysis of noctural arterial desaturation during the three first postoperative nights. RESULTS: The use of TEA resulted in fewer decrease both in FEV(1) (1.01+/-0.34 versus 1.31+/-0.51 l/s for Day 1, P=0.03; 1.13+/-0.37 versus 1.53+/-0.59 l/s for Day 2, P=0.01) and in FVC (1.23 [1.05-1.51] versus 1.57 [1.38 2.53] l for day 1, P=0.008; 1.33+/-0.43 versus 2.24+/-0.87 l for day 2, P<0.001). Moreover, the duration of arterial desaturation<90% were longer in the PCA group during the first (8.6 [0.8-28.2] versus 1.3 [0-2.6] min, P=0.02) and the second postoperative night (13.5 [3.5-54] versus 0.4 [0-2.6] min, P=0.025). CONCLUSION: The results of this study suggest that the use of TEA is associated with a better preservation of respiratory function assessed by spirometric data and noctural arterial desaturation recording after thoracic surgery for lobectomy. PMID- 17336491 TI - A P60 mutant of Listeria monocytogenes is impaired in its ability to cause infection in intragastrically inoculated mice. AB - A spontaneous P60 mutant of Listeria monocytogenes was less able to cause systemic infection in A/J mice, following intragastric inoculation, than the parental wild type strain (SLCC 5764, serotype 1/2a). Significantly fewer CFU were recovered from internal organs (spleen, liver, gall bladder) and from the cecum of mice inoculated intragastrically with the P60 mutant than mice inoculated with wild type L. monocytogenes. The P60 mutant also exhibited a diminished ability to invade and multiply within Caco-2 intestinal epithelial cells. These findings indicate that P60 is required for maximal virulence of L. monocytogenes in the gastrointestinal tract of mice. PMID- 17336492 TI - A sandwich-cultured rat hepatocyte system with increased metabolic competence evaluated by gene expression profiling. AB - A rapid decline of cytochrome P450 (CYP450) enzyme activities remains a drawback of rat hepatocyte-based in vitro cultures. Consequently, judgment of the toxic potential of compounds that need bioactivation by CYP450s may not be adequate using this model. In the present study, an improved hepatocyte-based in vitro system was developed with special focus on metabolic competence. Therefore, a mixture of CYP450 inducers, phenobarbital, dexamethasone and beta-naphthoflavone, was added to culture medium of sandwich-cultured rat hepatocytes. The resulting modified model was evaluated by comparing its genome-wide expression profiles with liver and a standard model without the inducer mixture. Metabolic capacity for CYP450 enzymes showed that the modified model resembled more closely the in vivo situation. Gene expression results revealed large differences between in vivo and both in vitro models. The slight differences between the two sandwich models were predominantly represented by gene expression changes in CYP450s. Importantly, in the modified model, expression ratios of the phase I and the majority of phase II genes more closely resembled liver in vivo. The CYP450 enzyme activities corresponded with gene expression data. In conclusion, for toxicological applications using sandwich-cultured hepatocytes, the modified model may be preferred. PMID- 17336493 TI - Trail Making Test in traumatic brain injury, schizophrenia, and normal ageing: sample comparisons and normative data. AB - The Trail Making Test (TMT) has been a useful assessment tool to investigate executive function. Several studies have recently improved the existing TMT norms by mean of large samples of healthy individuals stratified by a number of demographic variables from different populations. In contrast, criticisms have been raised about the utility of norms from healthy samples to detect changes across time in clinical samples where TMT performance used to be altered. In addition, few studies have compared groups of patients with deficits in TMT performance, making it difficult to decide whether a single set of norms is sufficient to assess different clinical populations. We provide normative data from three large samples of patients with traumatic brain injury (TBI) (n=90), schizophrenia spectrum disorders (n=127), and healthy Spanish speakers (n=223). Differences between healthy participants and patients in all TMT direct (TMT-A, TMT-B) and derived (B-A, B:A, B-A/A) scores were found. TMT performance was poorer in TBI patients than in schizophrenia patients except for the B:A and B A/A scores, suggesting a similar underlying executive deficit. Normal ageing impaired both direct and derived TMT indices, as revealed by lower scores in the healthy elderly group (55-80 years old) as compared with young (16-24) and middle aged (25-54) healthy participants. Three different sets of norms stratified by age, education, or both are presented for clinical use. Recommendations on TMT scores are made for future research. PMID- 17336494 TI - Discrepancies between self-reported years of education and estimated reading level among elderly community-dwelling African-Americans: Analysis of the MOAANS data. AB - The influence of education on cognition has received a great deal of attention in the literature. Although there is general consensus regarding the importance of education on cognitive functioning, the extent to which self-reported level of education corresponds to true educational attainment remains unclear, especially in ethnic minority populations where equal access to education has not always been available. Several investigators have suggested that reading skill may serve as a quantitative estimate of true education experience. Among African-Americans, however, research has shown that self-reported educational level consistently over predicts estimated reading level. The current study analyzed the discrepancy between self-reported years of education completed and estimated reading level in a sample of community-dwelling, elderly African-Americans participating in Mayo's Older African Americans Normative Studies (MOAANS) (Lucas, J.A., Ivnik, R.J., Willis, F.B., Ferman, T.J., Smith, G.E., Parfitt, F.C., Petersen, R.C., & Graff Radford, N.R. (2005). Mayo's Older African Americans Normative Studies: Normative data for commonly used clinical neuropsychological measures. The Clinical Neuropsychologist, 19, 162-183). In this sample, 29% of the participants read at a level that was 3 or more years below what would be expected based on self report of education attained. This study also sought to evaluate the extent to which this discrepancy fluctuated as a function of demographic variables such as location of schooling (urban, suburban, rural; North vs. South), parental education and literacy, and percentage of segregation in schooling. Implications of these results are discussed, as are areas for further inquiry. PMID- 17336495 TI - Simple alignment-free methods for protein classification: a case study from G protein-coupled receptors. AB - Computational methods of predicting protein functions rely on detecting similarities among proteins. However, sufficient sequence information is not always available for some protein families. For example, proteins of interest may be new members of a divergent protein family. The performance of protein classification methods could vary in such challenging situations. Using the G protein-coupled receptor superfamily as an example, we investigated the performance of several protein classifiers. Alignment-free classifiers based on support vector machines using simple amino acid compositions were effective in remote-similarity detection even from short fragmented sequences. Although it is computationally expensive, a support vector machine classifier using local pairwise alignment scores showed very good balanced performance. More commonly used profile hidden Markov models were generally highly specific and well suited to classifying well-established protein family members. It is suggested that different types of protein classifiers should be applied to gain the optimal mining power. PMID- 17336496 TI - Use of mutational pattern in 5'-NCR and VP1 regions of polioviruses for molecular diagnosis. AB - Polioviruses are members of the enterovirus genus, belonging to the Picornaviridae family. They are the causative agents of poliomyelitis, a paralytic and sometimes fatal disease in humans. The number of poliomyelitis cases caused by wild poliovirus infections has been dramatically reduced by the extensive use of two available vaccines: the inactivated poliovirus vaccine (IPV) and the oral poliovirus vaccine (OPV). Despite the importance of OPV in the reduction of poliomyelitis cases, one of the disadvantages associated with this vaccine is the rare occurrence of vaccine-associated paralytic poliomyelitis (VAPP) in vaccinees or their healthy contacts through the accumulation of mutations and/or recombination in Sabin strains genome. Thirteen clinical isolates originating from healthy vaccinees and VAPP cases were investigated in order to identify genomic modifications in 5' non-coding region (5'-NCR) and VP1 genomic regions. The analysis of samples was conducted by RT-PCR, RFLP, sequencing and bioinformatics analysis. All clinical isolates were characterized as OPV-like viruses. Our results showed that analysis of 5'-NCR and VP1 regions of Poliovirus Sabin strains is important in order to identify mutations that increase the neurovirulence conducting to the eventuality of emergence of VAPP cases. PMID- 17336497 TI - Prevalence and risk factors of constipation in adults with intellectual disability in residential care centers in Israel. AB - The normal aging process is not in itself a risk factor for constipation, but age related morbidities, immobility, neurologic impairment or specific drugs are risk factors for constipation. This study was undertaken to examine the prevalence and risk factors for constipation in a large sample of 2400 persons with intellectual disability (ID) aged 40 years and older living in residential care centers in Israel. Constipation was found in 8% of the total sample with no significant increase in the prevalence of constipation with age. Neurological disease, cerebral palsy, immobility and physical inactivity were risk factors associated with constipation. Mobility and physical activity is recommended in order to lower the prevalence of constipation in this population. PMID- 17336498 TI - Molecular mapping of autoimmune B cell responses in experimental myocarditis. AB - Autoimmune responses directed against heart-specific antigens most likely play a key role in the pathogenesis of myocarditis. Although autoantibodies against cardiac determinants are frequently detected both in human patients and mice suffering from myocarditis, the immunological mechanisms for their induction have not yet been fully explored. We used here the SEREX approach (serological identification of recombinantly expressed proteins) to molecularly dissect heart specific autoimmune B cell responses that develop in the course of experimentally induced myocarditis. Screening of a heart cDNA library with sera of cardiac myosin heavy chain alpha (myhcalpha) peptide-immunized BALB/c mice revealed a strong focusing of the B cell response on the myhcalpha protein. The vast majority of the myhcalpha transcripts coded for regions other than the sequence of the immunogenic myhcalpha peptide, indicating extensive intramolecular epitope spreading. Importantly, we found that the infection with cardiotropic viruses such as MCMV and Coxsackievirus B3 elicited specific autoantibody pattern with a particular skewing to the myhcalpha protein. The induction of myhcalpha peptide specific Th cells in the course of both infections suggests that infection associated determinant spreading on the Th cell level paves the way for a focused and dominant anti-myhcalpha B cell response. PMID- 17336499 TI - PKCdelta signaling: mechanisms of DNA damage response and apoptosis. AB - The cellular response to genotoxic stress that damages DNA includes cell cycle arrest, activation of DNA repair, and in the event of irreparable damage, induction of apoptosis. However, the signals that determine cell fate, that is, survival or apoptosis, are largely unknown. The delta isoform of protein kinase C (PKCdelta) has been implicated in many important cellular processes, including regulation of apoptotic cell death. The available information supports a model in which certain sensors of DNA lesions activate PKCdelta. This activation is triggered in part by tyrosine phosphorylation of PKCdelta by c-Abl tyrosine kinase. PKCdelta is further proteolytically activated by caspase-3. The cleaved catalytic fragment of PKCdelta translocates to the nucleus and induces apoptosis. Importantly, accumulating data have revealed the nuclear targets for PKCdelta in the induction of apoptosis. A pro-apoptotic function of activated PKCdelta is mediated by at least several downstream effectors known to be associated with the elicitation of apoptosis. Recent findings also demonstrated that PKCdelta is involved in cell cycle-specific activation and induction of apoptotic cell death. Moreover, previous studies have shown that PKCdelta regulates transcription by phosphorylating various transcription factors, including the p53 tumor suppressor that is critical for cell cycle arrest and apoptosis in response to DNA damage. These findings collectively support a pivotal role for PKCdelta in the induction of apoptosis with significant impact. This review is focused on the current views regarding the regulation of cell fate by PKCdelta signaling in response to DNA damage. PMID- 17336500 TI - Remission criteria for schizophrenia: evaluation in a large naturalistic cohort. AB - BACKGROUND: Recently, remission criteria for schizophrenia have been proposed, based on low symptom severity of core symptoms (severity criterion), sustained over minimally 6 months (time criterion). Little is known, however, about the added value of the time criterion in addition to the cross-sectional severity criterion. METHODS: In order to evaluate whether remission is a valid concept for daily clinical practice, the cumulative incidence of patients meeting remission criteria was evaluated in a large naturalistic prospective study of patients with schizophrenia or schizoaffective disorder in different treatment settings in Belgium. The impact of being in remission on global and daily functioning was evaluated. RESULTS: Over time, nearly 1 out of 3 patients with a diagnosis of schizophrenia or schizoaffective disorder (29%) met criteria for remission at study endpoint. Patients in remission had better insight in their disorder, a higher level of global functioning and functioned better with respect to daily living tasks, both compared to patients never meeting remission criteria and to patients only meeting the severity criterion but not the time criterion. Of the patients not meeting remission criteria at baseline, 21% attained remission at study endpoint. CONCLUSION: The remission severity and time criteria appear to combine into a valid concept for daily clinical practice and should be a target for treatment. PMID- 17336501 TI - PANSS rater training using Internet and videoconference: results from a pilot study. AB - Problems associated with the clinician-administered rating scales have led to new approaches to improve rater training. These include interactive, on-line didactic tutorials and live, remote evaluation of raters' clinical skills through the use of videoconferencing. The purpose of this study was to evaluate this approach in training novice raters on the administration of the Positive and Negative Symptom Scale (PANSS). Twelve trainees with no prior PANSS experience completed didactic training via CD-ROM and two remote training sessions where they interviewed a standardized patient-actor while being remotely observed in real time and given feedback. Results found a significant improvement in trainees' conceptual knowledge and an improvement in trainees' clinical skills. The use of these technologies allows for training to be more effectively delivered to diverse sites in multi-center trials, and for evaluation of raters' applied clinical skills, an area that has previously been overlooked. PMID- 17336502 TI - Increased hemodynamic response in the hippocampus, thalamus and prefrontal cortex during abnormal sensory gating in schizophrenia. AB - OBJECTIVE: Deficits in sensory gating are a common feature of schizophrenia. Failure of inhibitory gating mechanisms, shown by poor suppression of evoked responses to repeated auditory stimuli, has been previously studied using EEG methods. These methods yield information about the temporal characteristics of sensory gating deficits, but do not identify brain regions involved in the process. Hence, the neuroanatomical substrates of poor sensory gating in schizophrenia remain largely unknown. This study used functional magnetic resonance imaging (fMRI) to investigate the functional neuroanatomy of sensory gating deficits in schizophrenia. METHODS: Twelve patients with schizophrenia and 12 healthy comparison subjects were scanned at 3 Tesla while performing a sensory gating task developed for fMRI. P50 EEG evoked potential recordings from a paired stimulus conditioning-test paradigm were obtained from the same subjects. RESULTS: Compared to healthy comparison subjects, patients with schizophrenia exhibited greater activation in the hippocampus, thalamus, and dorsolateral prefrontal cortex (DLPFC) during the fMRI sensory gating task. No group difference was observed in the superior temporal gyrus. Schizophrenia subjects also showed decreased P50 suppression as measured with EEG. Hemodynamic response in the fMRI measure was positively correlated with test/conditioning ratios from the EEG sensory gating measure. CONCLUSIONS: Poor sensory gating in schizophrenia is associated with dysfunction of an apparent network of brain regions, including the hippocampus, thalamus and DLPFC. Greater activation of these regions is consistent with evidence for diminished inhibitory function in schizophrenia. PMID- 17336503 TI - A novel missense mutation in COL7A1 in a Chinese pedigree with epidermolysis bullosa pruriginosa. PMID- 17336504 TI - Efficacy of repeated cycles of combination therapy for the eradication of infecting organisms in chronic bacterial prostatitis. AB - A total of 137 patients with a diagnosis of chronic bacterial prostatitis (CBP) were subjected to combination pharmacological therapy with antibacterial agents (ciprofloxacin/azithromycin), alpha-blockers (alfuzosin) and Serenoa repens extracts. Of those, 88 patients (64.2%) showed microbiological eradication at the completion of a 6-week cycle of therapy. Of the remaining 49 patients showing persistence of the causative organism(s) or reinfection at the end of treatment, 36 completed a second cycle of combination therapy for 6 weeks: 27 patients (75%) showed eradication of the causative organism, whereas in nine cases persistence or reinfection was observed. The cumulative eradication rate of the present study - calculated on a total of 137 enrolled patients - is 83.9%. Clinical examination showed a marked improvement of signs and symptoms linked to prostatitis. Remarkably, combination therapy could attenuate CBP symptoms prior to microbiological eradication, thus rapidly decreasing the impact of the disease on the quality of life of patients. Clinical remission was extended throughout a follow-up period of 30 months for 94% of patients, whereas seven patients showed relapse of the disease. In summary, our results indicate that about 20% of patients enrolled in this study, who were refractory to a protocol of 6-week combination therapy, could be 'rescued' by a second cycle of treatment. Clinical follow-up data show that combination therapy could ensure extended relief from CBP symptoms, and a general improvement in quality of life. PMID- 17336505 TI - Micellization of bile salts in aqueous medium: a fluorescence study. AB - Owing to the physiological importance of the micellization process of bile salts, the critical micelle concentration (CMC) becomes a fundamental parameter in the evaluation of their biological activities. The present study suggests fluorescence probing, using 1,6-diphenylhexatriene (DPH), as a simple, convenient, sensitive and economic method for monitoring the micellization process of bile salts in aqueous medium. Three independent parameters: fluorescence intensity, anisotropy and lifetime of DPH have been employed successfully for determining the CMC of two bile salts, sodium deoxycholate (NaDC) and sodium cholate (NaC), in aqueous medium. The CMC values reported by all the above three parameters of DPH are found to be same and it is 16 mM for NaC and 6 mM for NaDC at 25 degrees C in unbuffered solution. The effect of temperature and ionic strength on the micellization process has also been investigated employing DPH as a fluorescent probe. Increasing temperature leads to the formation of fluffier micelles with less rigid interior for both NaC and NaDC. The micelle core of NaC is less perturbed by the presence of NaCl whereas in case of NaDC, the aggregates provide DPH a more nonpolar and rigid environment in presence of NaCl than that in absence of salt. PMID- 17336506 TI - Invariance and selectivity in the ventral visual pathway. AB - Pattern recognition systems that are invariant to shape, pose, lighting and texture are never sufficiently selective; they suffer a high rate of "false alarms". How are biological vision systems both invariant and selective? Specifically, how are proper arrangements of sub-patterns distinguished from the chance arrangements that defeat selectivity in artificial systems? The answer may lie in the nonlinear dynamics that characterize complex and other invariant cell types: these cells are temporarily more receptive to some inputs than to others (functional connectivity). One consequence is that pairs of such cells with overlapping receptive fields will possess a related property that might be termed functional common input. Functional common input would induce high correlation exactly when there is a match in the sub-patterns appearing in the overlapping receptive fields. These correlations, possibly expressed as a partial and highly local synchrony, would preserve the selectivity otherwise lost to invariance. PMID- 17336507 TI - Adherence to a healthful life attenuates lipid parameters among a healthy Italian population. AB - BACKGROUND AND AIM: During the last 5 years, an increasing body of evidence on the association between adherence to the Mediterranean diet (MD), calculated through specific diet scores, and health status have been accumulated, but limited data are available regarding the association between MD scores and biomarkers. Similarly, many studies have demonstrated a significant protection against chronic diseases from a global healthy lifestyle (HL) pattern which includes not only dietary habits but also physical activity and abstinence from smoking, whereas few data regarding the influence of a HL pattern on circulating biomarkers are available. Using the framework of an epidemiological study conducted in Florence, Italy between 2002 and 2004 we evaluated the association between two different scores (a score of adherence to the MD and a score of adherence to a healthful life which includes abstinence from smoking and a moderate-to-high physical activity level) and some circulating parameters linked to chronic diseases. METHODS AND RESULTS: Dietary habits and anthropometric and biochemical profiles were studied in 932 individuals (365 M; 567 F) with a median age of 47.5 years. Subjects who reported a greater adherence to the MD were found more frequently to be male, married and over 45 years of age. A general linear model dividing the study population into quartiles of scores was used. After adjustment for age, gender, educational status, body mass index and total energy intake, we observed no influence of adherence to the MD on circulating levels of biomarkers. On the other hand, an inverse association between circulating levels of lipid parameters (namely total cholesterol, LDL-cholesterol and triglycerides) and higher scores of adherence to a HL, was reported. In addition, a significant difference between the highest and the lowest quartiles of HL scores for homocysteine plasma levels was observed (p=0.04). CONCLUSION: A high adherence to a HL, which includes not only a high adherence to the MD but also to other lifestyle factors (i.e. abstinence from smoking, and increasing physical activity during leisure time), is able to lower lipid parameters and homocysteine in a clinically healthy Italian population. PMID- 17336508 TI - Physical activity: an effective way to control weight in children? AB - Physical activity is the only component of total energy expenditure that can be voluntarily modified. Therefore, it is a reasonable behavioral target for the prevention and treatment of obesity. Most of the fat oxidized daily in the body occurs in skeletal muscle. Physical activity increases the amount of oxidized fat, which helps control fat mass. Moreover, skeletal muscle is an efficient blood glucose utilizer, and regular physical activity promotes insulin sensitivity and glucose homeostasis independently of its effect on body fat. The primary purpose of this study was to provide further insight into the metabolic effects of physical activity, especially on the regulation of energy expenditure, substrate oxidation and body composition. Also of interest is the analysis of available evidence that justifies the recommendation of physical activity programs in the treatment of childhood obesity. PMID- 17336509 TI - Determinants of lung function and airway hyperresponsiveness in asthmatic children. AB - BACKGROUND: Asthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying effect of steroid treatment. METHODS: We analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma Genetic Study (SAGA). RESULTS: The primary analysis studied the association between the lung function and delay of inhaled corticosteroids (ICS) after asthma diagnosis among asthmatic children and young adults with a history of regular ICS treatment (N=919). FEV(1) percent predicted (FEV(1)% pred) was 0.25% lower per year of delay from diagnosis until treatment (p=0.039). This association was significantly greater in allergy skin prick test negative children. There was no significant influence of gender, age at asthma onset, or smoking. In the secondary analysis of the whole population of 2390 asthmatics and non-asthmatics, FEV(1)% pred was inversely related to having asthmatic siblings (-7.9%; p<0.0001), asthma diagnosis (-2.7%; p=0.0007), smoking (-3.5%; p=0.0027), and positive allergy skin prick test ( 0.47% per test; p=0.012), while positively related to being of female gender (1.8%; p=0.0029). Risk of AHR was higher by having asthmatic siblings (OR 2.7; p<0.0001), being of female gender (OR 2.0; p<0.0001), and having asthma (OR 2.0; p<0.0001). CONCLUSIONS: These data suggest that lung function is lower in asthmatics with delayed introduction of ICS therapy, smoking, and positive allergy skin prick test. Lung function is lower and AHR higher in female asthmatics and subjects with asthmatic siblings or established asthma. PMID- 17336510 TI - Fermentation technologies for the production of probiotics with high viability and functionality. AB - There is growing scientific evidence supported by mechanistic and clinical studies that probiotics can provide health benefits. As probiotics are highly sensitive to many environmental factors, and because the propagation of many strains of intestinal origin is not straightforward, most commercial strains are selected on the basis of their technological properties - ruling out some strains with promising health properties. To date, probiotic production has almost exclusively been carried out using conventional batch fermentation and suspended cultures, in some cases combined with the use of sublethal stresses to enhance cell viability, the addition of protectants or microencapsulation to provide cell protection. However, other less conventional fermentation technologies, such as continuous culture and immobilized cell systems, could have potential for enhancing the performance of these fastidious organisms. These technologies might be employed to develop strains with improved physiology and functionality in the gut and to enlarge the range of commercially available probiotics, as well as expanding product applications. PMID- 17336511 TI - Chromatin organization and differentiation in embryonic stem cell models. AB - Embryonic stem cells derived from mammalian embryos represent indispensable tools for mammalian genetics. Their key features--self-renewal and pluripotency--enable them, on the one hand, to be propagated in culture almost indefinitely and, on the other, to be used to study the molecular details of cell commitment and differentiation. In the past few years, it has become clear that chromatin and epigenetic modifications have a central role in maintaining the gene expression programs that are important for both self-renewal and cell commitment. Therefore, studies focused on the chromatin profiles of embryonic stem cells are likely to be very informative for understanding pluripotency and the process of differentiation, and ultimately for using embryonic stem cells as a tool for cell replacement therapy or as models for the study of genetic diseases, cancer progression or drug testing. PMID- 17336512 TI - Role of anticipated reward in cognitive behavioral control. AB - The lateral prefrontal cortex (LPFC), which is important for higher cognitive activity, is also concerned with motivational operations; this is exemplified by its activity in relation to expectancy of rewards. In the LPFC, motivational information is integrated with cognitive information, as demonstrated by the enhancement of working-memory-related activity by reward expectancy. Such activity would be expected to induce changes in attention and, subsequently, to modify behavioral performance. Recently, the effects of motivation and emotion on neural activities have been examined in several areas of the brain in relation to cognitive-task performance. Of these areas, the LPFC seems to have the most important role in adaptive goal-directed behavior, by sending top-down attention control signals to other areas of the brain. PMID- 17336513 TI - The neuroscience of remote memory. AB - Recently, there has been renewed interest in the organization and neurobiology of remote memory, and the pace of work in this area has accelerated. Yet the recent literature does not suggest that a consensus is developing, and there is disagreement about both facts and their interpretation. This article undertakes a comprehensive review of the three kinds of evidence that have been most prominent in recent discussion: studies of retrograde amnesia in memory-impaired patients who have well-characterized lesions, neuroimaging of healthy volunteers, and work with experimental animals including lesion studies, imaging and mouse genetics. The available evidence tells a coherent story and leads to some straightforward conclusions about the neuroscience of remote memory. PMID- 17336514 TI - Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005. AB - Recent publications have suggested that imatinib (Glivec) may be cardiotoxic. We have therefore assessed the largest study on the agent performed in patients with gastrointestinal stromal tumours, randomising a daily dose of 400mg versus 800 mg. 946 Patients were entered, 942 patients received at least one dose of imatinib. The median time on treatment was 24 months. A total of 24,574 exposure months could be analysed. We could not identify an excess of cardiac events in the study population. In 2 patients (0.2%) a possible cardiotoxic effect of imatinib could not fully be excluded. The current analysis of a large randomised prospective study could not confirm previous suggestions of imatinib induced cardiac toxicity. PMID- 17336515 TI - Agro-industrial waste materials and wastewater sludge for rhizobial inoculant production: a review. AB - Inoculating legumes with commercial rhizobial inoculants is a common agriculture practice. Generally, inoculants are sold in liquid or in solid forms (mixed with carrier). The production of inoculants involves a step in which a high number of cells are produced, followed by the product formulation. This process is largely governed by the cost related to the medium used for rhizobial growth and by the availability of a carrier source (peat) for production of solid inoculant. Some industrial and agricultural by-products (e.g. cheese whey, malt sprouts) contain growth factors such as nitrogen and carbon, which can support growth of rhizobia. Other agro-industrial wastes (e.g. plant compost, filtermud, fly-ash) can be used as a carrier for rhizobial inoculant. More recently, wastewater sludge, a worldwide recyclable waste, has shown good potential for inoculant production as a growth medium and as a carrier (dehydrated sludge). Sludge usually contains nutrient elements at concentrations sufficient to sustain rhizobial growth and heavy metals are usually below the recommended level. In some cases, growth conditions can be optimized by a sludge pre-treatment or by the addition of nutrients. Inoculants produced in wastewater sludge are efficient for nodulation and nitrogen fixation with legumes as compared to standard inoculants. This new approach described in this review offers a safe environmental alternative for both waste treatment/disposal and inoculant production. PMID- 17336516 TI - Feasibility of nitrification/denitrification in a sequencing batch biofilm reactor with liquid circulation applied to post-treatment. AB - An investigation was performed on the biological removal of ammonium nitrogen from synthetic wastewater by the simultaneous nitrification/denitrification (SND) process, using a sequencing batch biofilm reactor (SBBR). System behavior was analyzed as to the effects of sludge type used as inoculum (autotrophic/heterotrophic), wastewater feed strategy (batch/fed-batch) and aeration strategy (continuous/intermittent). The presence of an autotrophic aerobic sludge showed to be essential for nitrification startup, despite publications stating the existence of heterotrophic organisms capable of nitrifying organic and inorganic nitrogen compounds at low dissolved oxygen concentrations. As to feed strategy, batch operation (synthetic wastewater containing 100 mg COD/L and 50 mg N-NH(4)(+)/L) followed by fed-batch (synthetic wastewater with 100 mg COD/L) during a whole cycle seemed to be the most adequate, mainly during the denitrification phase. Regarding aeration strategy, an intermittent mode, with dissolved oxygen concentration of 2.0mg/L in the aeration phase, showed the best results. Under these optimal conditions, 97% of influent ammonium nitrogen (80% of total nitrogen) was removed at a rate of 86.5 mg N-NH(4)(+)/Ld. In the treated effluent only 0.2 mg N-NO(2)(-)/L,4.6 mg N NO(3)(-)/L and 1.0 mg N-NH(4)(+)/L remained, demonstrating the potential viability of this process in post-treatment of wastewaters containing ammonium nitrogen. PMID- 17336517 TI - Biosorption of hexavalent chromium onto raw and chemically modified Sargassum sp. AB - Hexavalent chromium biosorption by raw algae is always accompanied with significantly high organic leaching. In this study, hydrochloric acid, sodium hydroxide, calcium chloride, formaldehyde, and glutaraldehyde were used for modification of raw Sargassum sp. seaweed (RSW), in order that the modified seaweed (MSW) has a lower organic leaching while the metal biosorption capacity is comparable to the RSW. The result shows that the chemical modification by 0.2% formaldehyde achieves such goals. The biosorption of both RSW and MSW is highly pH dependent. At the optimal pH of 2.0, the maximum biosorption capacities of MSW and RSW are 1.123 and 0.601 mmol g(-1), respectively. The surface treatment improves the reduction capacity of the biosorbents. The instrumental analysis demonstrates that the Cr(VI) biosorption is controlled by redox, ion exchange and coordination reactions, of which alcohol, carboxyl, amino and sulphonic groups play important roles. The complete uptake of hexavalent chromium is achieved in 20 h. The chemical reduction for Cr(VI) to Cr(III) is pH dependent and controls the overall chromium removal kinetics. PMID- 17336518 TI - Design, synthesis, and bioactivity of novel inhibitors of E. coli aspartate transcarbamoylase. AB - A series of inhibitors of the aspartate transcarbamoylase, an enzyme involved in pyrimidine nucleotide biosynthesis, has been synthesized. These inhibitors are analogues of a highly potent inhibitor of this enzyme, N-phosphonacetyl-L aspartate (PALA). Analogues have been synthesized with modifications at the alpha and beta-carboxylates as well as at the aspartate moiety. The ability of these compounds to inhibit the enzyme was evaluated. These studies, with functional group modified PALA derivatives, showed that amide groups can be a useful substitute of the carboxylate in order to reduce the charge on the molecule, and indicate that the relative position of the functional group in the beta-position is more critical than the nature of the functional group. Some of the molecules synthesized here are potent inhibitors of the enzyme. PMID- 17336519 TI - Synthesis and biological evaluation of nucleoside analogues having 6-chloropurine as anti-SARS-CoV agents. AB - Nucleoside analogues that have 6-chloropurine as the nucleobase were synthesized and evaluated for anti-SARS-CoV activity by plaque reduction and yield reduction assays in order to develop novel anti-SARS-CoV agents. Among these analogues, two compounds, namely, 1 and 11, exhibited promising anti-SARS-CoV activity that was comparable to those of mizoribine and ribavirin, which are known anti-SARS-CoV agents. Moreover, we observed several SAR trends such as the antiviral effects of the 6-chloropurine moiety, unprotected 5'-hydroxyl group and benzoylated 5' hydroxyl group. PMID- 17336520 TI - Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists. AB - A series of heterobiaryl amides was designed and synthesized as novel mGluR5 antagonists. The synthesis using palladium catalyzed Suzuki-Miyaura cross coupling reactions provided an array of compounds with a range of in vitro activities. In particular, compound 9e, 4(3,5-difluorophenyl)-N-(6-methylpyridin 1-yl)picolinamide, exhibited nanomolar affinity at the mGluR5 and will serve as a template for future drug design. PMID- 17336521 TI - Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: structural recognition of STAT SH2 domains. AB - The identification of constitutively activated STAT (Signal Transducers and Activators of Transcription) proteins in aberrant cell signaling pathways has led to investigations targeting the selective disruption of specific STAT isoforms directly associated with oncogenisis. We have identified, through the design of a library of peptidomimetic inhibitors, agents that selectively disrupt STAT1 or STAT3 homo-dimerization at low micromolar concentrations. ISS840 has 20-fold higher inhibition of STAT1 homo-dimerization (IC(50) value of 31 microM) relative to STAT3 (IC(50) value of 560 microM). PMID- 17336522 TI - Synthesis and biological evaluation of novel analogues of dictyostatin. AB - Novel analogues of the microtubule-stabilising agent dictyostatin were designed using existing SAR information from the structurally related discodermolide, synthesised by a late-stage diversification strategy and evaluated in vitro for growth inhibition against a range of human cancer cell lines, including those known to exhibit Taxol-resistance (AsPC-1, DLD-1, PANC-1, NCI/ADR). PMID- 17336523 TI - The rational design of inhibitors of nitric oxide formation by inducible nitric oxide synthase. AB - A series of compounds was rationally designed as inhibitors of dimer formation of the inducible isoform of nitric oxide synthase, and subsequent nitric oxide production. The conformation of two fragments obtained from a crystal structure was utilized to design a tether connecting those same two fragments. The resulting compounds were potent dimerization inhibitors that bound to the enzyme in a similar conformation as the fragments. PMID- 17336524 TI - Cell differentiation enhancement by hydrophilic derivatives of 4,8 dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-diones in HL-60 leukemia cells. AB - Among five carboxamide derivatives (13-17), N-(2-dimethylaminoethyl)-4,8 dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione-2-carboxamide (13) showed the greatest enhancement of all-trans retinoid acid (ATRA)-induced differentiation in HL-60 cells, inducing nearly complete differentiation at a concentration of 0.02microM. On the other hand, 2-hydroxymethyl-4,8-dihydrobenzo[1,2-b:5,4 b']dithiophene-4,8-dione (2) and 2-(1-hydroxylethyl)-4,8-dihydrobenzo[1,2-b:5,4 b']dithiophene-4,8-dione (18) exhibited excellent and equally potent differentiation effects on HL-60 cells. To improve their water solubility, ester type hydrophilic prodrugs (23-26) were also synthesized. Compounds 13 and 23-26 are identified in this paper as new anti-leukemic drug candidates. PMID- 17336525 TI - Myostatin does not regulate cardiac hypertrophy or fibrosis. AB - Myostatin is a negative regulator of muscle growth. Loss of myostatin has been shown to cause increase in skeletal muscle size and improve skeletal muscle function and fibrosis in the dystrophin-deficient mdx muscular dystrophy mouse model. We evaluated whether lack of myostatin has an impact on cardiac muscle growth and fibrosis in vivo. Using genetically modified mice we assessed whether myostatin absence induces similar beneficial effects on cardiac function and fibrosis. Cardiac mass and ejection fraction were measured in wild-type, myostatin-null, mdx and double mutant mdx/myostatin-null mice by high resolution echocardiography. Heart mass, myocyte area and extent of cardiac fibrosis were determined post mortem. Myostatin-null mice do not demonstrate ventricular hypertrophy when compared to wild-type mice as shown by echocardiography (ventricular mass 0.69+/-0.01 vs. 0.69+/-0.018 g) and morphometric analyses including heart/body weight ratio (5.39+/-0.45 vs. 5.62+/-0.58 mg/g) and cardiomyocyte area 113.67+/-1.5, 116.85+/-1.9 microm(2)). Moreover, absence of myostatin does not attenuate cardiac fibrosis in the dystrophin-deficient mdx mouse (12.2% vs. 12%). The physiological role of myostatin in cardiac muscle appears significantly different than that in skeletal muscle as it does not induce cardiac hypertrophy and does not modulate cardiac fibrosis in mdx mice. PMID- 17336526 TI - MYH7 gene mutation in myosin storage myopathy and scapulo-peroneal myopathy. AB - In order to characterize, at the clinical, molecular and imaging level, myopathies due to MYH7 gene mutations, MYH7 gene analysis was conducted by RT PCR/SSCP/sequencing in two patients diagnosed with myosin storage myopathy and 17 patients diagnosed with scapulo-peroneal myopathy of unknown etiology. MYH7 gene studies revealed the 5533C>T mutation (Arg1845Trp) in both myosin storage myopathy and in 2 of the 17 scapulo-peroneal patients studied. 5533C>T segregation analysis in the mutation carrier families identified 11 additional patients. The clinical spectrum in our cohort of patients included asymptomatic hyperCKemia, scapulo-peroneal myopathy and proximal and distal myopathy with muscle hypertrophy. Muscle MRI identified a unique pattern in the posterior compartment of the thigh, characterized by early involvement of the biceps femoris and semimembranosus, with relative sparing of the semitendinosus. Muscle biopsy revealed hyaline bodies in only half of biopsied patients (2/4). In conclusion, phenotypic and histopathological variability may underlie MYH7 gene mutation and the absence of hyaline bodies in muscle biopsies does not rule out MYH7 gene mutations. PMID- 17336527 TI - Clinical outcome of severe head injury in different protocol-driven therapies. AB - In the past 5 years cerebral perfusion pressure (CPP) management has become mainstream in the treatment of severe head injuries. The American Association of Neurological Surgeons guidelines (2000) suggest that CPP should be maintained at least 70 mmHg; however, there is still debate about optimal CPP level. The purpose of this study is to evaluate the effectiveness of three widely used therapies: intracranial pressure (ICP)-targeted therapy, CPP-targeted therapy with CPP > 70 mmHg, and modified CPP-targeted therapy with CPP > 60 mmHg. The clinical procedures, complications, and patient outcomes are compared. Data including patient age, sex, initial Glasgow Coma Score (GCS), ICP, CPP, fluid status, amount of mannitol and vasopressor used, daily intake and output, complications, and clinical results were collected from 213 patients with severe head injuries over a 12-year period. Patients were categorized into three groups (ICP, CPP, modified CPP [mCPP]) according to treatment protocol used. Retrospective data collection was by chart review. The mortality rate was 28.6%, 14.3%, and 13.5% in groups ICP, CPP, and mCPP, respectively. Highest intake/output ratio, amount of vasopressor used, and pulmonary complication rates were seen in group CPP patients. Group mCPP patients showed the best clinical outcome and lowest complication rate. Though CPP-targeted therapy is the most recommended therapeutic protocol, our data showed that the outcome is as good in the mCPP-targeted group with CPP > 60 mmHg as in the CPP-targeted group, but complications are fewer in the mCPP group. PMID- 17336528 TI - Management of cervicomedullary compression in patients with congenital and acquired osseous-ligamentous pathologies. AB - We present our experience in the diagnosis, surgical management and long-term follow-up of congenital and acquired osseous-ligamentous abnormalities or pathologies of the craniovertebral junction. The purpose of this study was: (i) to determine the incidence and degree of cervicomedullary compression in pediatric and young adult patients with congenital and acquired abnormalities, and (ii) to correlate cervicomedullary compression with other imaging and clinical factors to determine to what extend cervicomedullary compression is successfully treated with a posterior decompressive procedure, transoral decompression, and medical management. Between January 1995 and December 2004, 26 cases were managed in our department. These patients had: rheumatoid arthritis (RA) (3); traumatic injury (2); congenital basilar impression (5, in 2 cases a posteriorly oriented or retroflexed odontoid); infection (10); craniovertebral junction Pott's disease (9); os odonteideum (3); condylus tertius (1); and tumor (2). Six of the patients (23.1%) had syringomyelia. Only three (11.3%) were in the pediatric age group. Symptoms and signs included headache (72%), ataxia (38%), lower cranial nerve dysfunction (54%), quadriparesis (44%), hyperreflexia (76%), Hoffman positivity (72%), achilles clonus (72%) nystagmus (33%) and dysphagia (22%). The mean follow-up time was 44 months (range 3-85). Twelve (46.2%) had undergone posterior fossa decompression; seven (26.6%) had ventral decompression. Seven of the patients (26.6%) had medical management. The major morbidity included pharyngeal wound sepsis leading to dehiscence (3.8%), valopharyngeal insufficiency (3.8%), cerebrospinal fluid leakage (3.8%), postoperative macroglossia (3.8%) and inadequate anterior decompression (3.8%). Transient neurological deterioration occurred in two patients (7.6%). Our management paradigm will result in some neurologic improvements and limit the progression of symptoms. Patients with these pathologies are likely to show a good neurologic outcome when treatment, whether with or without surgery, is administered early in the course of the disease. PMID- 17336529 TI - Longitudinal prevalence and determinants of early mood disorder post-stroke. AB - BACKGROUND: Early identification of mood disorder post-stroke (MDPS) or its determinants could improve stroke outcomes. However, the natural history, prevalence and determinants of MDPS within the first weeks post-stroke require further investigation. METHODS: Consecutive hospitalised stroke survivors were assessed within 2-5 days of stroke, and at 1 and 3 months post-stroke. Baseline data included demographics, co-morbidities, stroke subtype, pre-stroke disability and cognition. At baseline, 1- and 3-month interviews physical impairment, disability, cognition and social support were assessed. MDPS was defined as a score of >8 on the depression subscale of the Hospital Anxiety Depression Scale. Factors independently associated with MDPS at each time-point were determined using regression analyses. RESULTS: One hundred and twenty-five subjects were included. The prevalence of MDPS within 5 days and at 1 and 3 months post-stroke was 5%, 16% and 21% respectively. The independent determinants for MDPS at 1 month were disability, social support and change in impairment score between initial and 1-month assessments; and at 3 months were disability, social support and institutionalisation. Individuals moved in and out of the subset of depressed patients over time. MDPS was independently associated with mortality at 3 months post-stroke. CONCLUSION: Mood disorder post-stroke increases in prevalence over the initial weeks post-stroke despite an improvement in disability, and is associated with mortality. Patients with MDPS at 1 month were not necessarily affected at 3 months and vice versa, indicating the dynamic nature of MDPS in the early stages. PMID- 17336530 TI - Inducible heat shock protein 70, interleukin-18, and tumor necrosis factor alpha correlate with outcomes in spontaneous intracerebral hemorrhage. AB - Inducible heat shock protein 70 (HSP70), a stress protein detected in the central nervous system, is expressed when a cell or organism is under stress. Interleukin 18 (IL-18) and tumor necrosis factor alpha (TNF-alpha) are multipotential early proinflammatory cytokines. Our objective was to determine protein levels of HSP70, IL-18, and TNF-alpha as well as mRNA levels of HSP70, IL-18, and TNF-alpha in the plasma and CSF of spontaneous intracerebral hemorrhage (ICH) patients, and to correlate these with disease outcome. Serial measurement of the proteins in CSF and plasma and of the mRNAs in peripheral blood mononuclear cells was conducted in 43 patients (mean age, 64+/-9 years; 23 men and 20 women). Ten (23%) patients died. We found that the damaged brain releases TNF-alpha and HSP70 to the peripheral blood and that plasma levels of these are highly associated with mortality in spontaneous ICH patients. PMID- 17336531 TI - Bradycardia due to hydrogen peroxide irrigation during craniotomy for craniopharyngioma. AB - Complications of hydrogen peroxide have been described in the literature and typically involve the effects of O(2) emboli. We report a 15-year-old male patient undergoing right frontal craniotomy and excision of craniopharyngioma. A sudden bradycardia occurred after instillation of hydrogen peroxide solution at the surgical site. Stimulation of the anterior hypothalamus after removal of the tumor and hydrogen peroxide irrigation may have triggered intense parasympathetic activity leading to bradycardia. The other possible causes for the complication are discussed. PMID- 17336532 TI - Quantitative structure-activity relationship of sesquiterpene lactones with cytotoxic activity. AB - Some sesquiterpene lactones (SLs) are the active compounds of a great number of traditionally medicinal plants from the Asteraceae family and possess considerable cytotoxic activity. Several studies in vitro have shown the inhibitory activity against cells derived from human carcinoma of the nasopharynx (KB). In this study, we investigated a set of 37 different sesquiterpene lactones, represented by 4 skeletons (14 germacranolides, 6 elemanolides, 9 guaianolides and nor-derivatives, and 8 pseudoguaianolides), in what it says respect of their cytotoxic properties. The experimental results were submitted to a QSAR study. A single model for the entire data set was described using 3D molecular descriptors and genetic algorithms establishing structure-activity relationships among the compounds. Important properties for the inhibition potency are discussed for the whole data set and for subsets of the different structural skeletons. PMID- 17336533 TI - Chemical synthesis and biological activities of 16alpha-derivatives of 5alpha androstane-3alpha,17beta-diol as antiandrogens. AB - In our efforts to develop compounds with therapeutic potential as antiandrogens, we synthesized a series of 5alpha-androstane-3alpha,17beta-diol derivatives with a fixed side-chain length of 3-methylenes at C-16alpha, but bearing a diversity of functional groups at the end. Among these, the chloride induced the best antiproliferative activity on androgen-sensitive Shionogi cells. Substituting the OH at C-3 by a methoxy group showed the importance of the OH. Moreover, its transformation into a ketone increased the androgen receptor (AR) binding but decreased the antiproliferative activity and induced a proliferative effect on Shionogi cells. These results confirm the importance of keeping a 5alpha androstane-3alpha,17beta-diol nucleus instead of a dihydrotestosterone nucleus. Variable side-chain lengths of 2-, 3-, 4-, and 6-methylenes at C-16alpha were investigated and the optimal length was found to be 3-methylenes. Although exhibiting a weak AR binding affinity, 16alpha-(3'-chloropropyl)-5alpha androstane-3alpha,17beta-diol (15) provided an antiproliferative activity on Shionogi cells similar to that of pure non-steroidal antiandrogen hydroxy flutamide (77% and 67%, respectively, at 0.1 microM). The new steroidal compound, 15, thus constitutes a good starting point for development of future antiandrogens with a therapeutic potential against prostate cancer. PMID- 17336534 TI - Clavaminols A-F, novel cytotoxic 2-amino-3-alkanols from the ascidian Clavelina phlegraea. AB - The chemical investigation of the Mediterranean ascidian Clavelina phlegraea has led to the isolation of six new 2-amino-3-alkanol derivatives, clavaminols A-F (1 6). Their stereostructures were established by analysis of spectroscopic data and chemical conversion. Clavaminols A, B, C, and F were tested for their cytotoxic and pro-apoptotic properties and clavaminol A was shown to be the more potent cytotoxic compound of this series inducing cell death through activation of the apoptotic machinery. PMID- 17336535 TI - Structure-activity based study of the Smac-binding pocket within the BIR3 domain of XIAP. AB - A small series of peptide mimics was designed and synthesized to contain a heterocyclic ring in place of the potentially labile N-terminal peptide bond of the tetrapeptide containing the Smac-XIAP-binding motif. Two Smac mimics were shown to bind to the BIR3 domain of XIAP with moderate affinity and one displayed increased activity in cells relative to the Smac peptides. The structures of BIR3 XIAP in complex with a Smac peptide and a peptide mimic were solved and analyzed to elucidate the structure-activity relationship surrounding the Smac-binding domain within BIR3-XIAP. PMID- 17336536 TI - Novel 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines: synthesis, selectively analgesic action, and QSAR analysis. AB - Based on the knowledge that imidazoline can result in analgesic action due to its selective binding with the prostacyclin receptor, 20 1-oxyl-2-substitutedphenyl 4,4,5,5-tetramethylimidazolines (3a-t) were prepared in moderate yields. At 0.13 mmol/kg dose, their in vivo analgesic activities were evaluated after the mice were administered at 30, 60, 90, and 150 min. Compared with the pain threshold (12.27+/-9.56-17.71+/-7.00%) of normal saline (NS) receiving mice, the pain threshold (23.42+/-8.14% to 102.58+/-10.66%) of 3a-t receiving mice increases significantly. Considering a prostacyclin receptor targeting analgesic agent usually had bleeding action and to appraise the bleeding risk, the in vivo tail bleeding time of 1.30 mmol/kg 3a-t receiving mice was found to be ranged from 116.3+/-8.2s to 120.3+/-9.2s, which was substantially equal to that (117.8+/-8.4s to 119.0+/-8.6s) of NS receiving mice. Based on the possibility of imidazoline acting as vasodilator, the in vitro vasorelaxations of 3a-t were tested using the rat aortic strip model. When the aortic strip contracted by noradrenaline (NE, final concentration 10(-7)mol/l) was treated with 3a-t (final concentration 5 x 10(-4)mol/l), only lower percentage inhibitions (6.55+/-5.70-37.40+/-4.07%) were recorded, implying that the vasorelaxation of 3a-t was neglectable. By selecting appropriate molecular descriptors generated from e-dragon server, the QSAR model of the analgesic activities of 3a-t was constructed using the multiple linear regression method. The established QSAR model showed reasonable accuracy and thus it is promising to be used for screening new 1-oxyl-2-substitutedphenyl-4,4,5,5 tetramethylimidazoline derivatives as analgesic agents. PMID- 17336537 TI - A potential dating technique using 228Th/228Ra ratio for tracing the chronosequence of elemental concentrations in plants. AB - We propose a radiometric method based on measurement of the radioactivity of the naturally occurring radionuclides (228)Ra and 228)Th and the derived (228)Th/(228)Ra ratios in plant samples to estimate plant age and the corresponding nutritional conditions in a field-growing fern, Dicranopteris linearis. Plant age (tissue age) was associated with the (228)Th/(228)Ra ratio in fronds, which implies the accumulation time of immobile elements in the plant tissue or the life span of the fronds. Results indicated that the accumulation of alkaline earth elements in D. linearis is relatively constant with increased age, while the K concentration is reversed with age because of translocation among plant tissues. Estimation of dating uncertainty based on measurement conditions revealed that the radiometric technique can be applied to trace chronosequential changes of elemental concentrations and environmental pollutants in plants with ages of less than 10-15 years. PMID- 17336538 TI - Surgical and long-term mortality in 2634 consecutive patients operated on the proximal thoracic aorta. AB - OBJECTIVE: To assess surgical and long-term mortality in a large, contemporary, unselected cohort of patients undergoing operations on the proximal thoracic aorta. METHODS: Patients in the Swedish Heart Surgery register operated 1992-2004 were identified and data cross-linked with the in-hospital and cause-of-death registers. Factors associated with surgical, intermediate, and long-term mortality were studied with separate Cox analyses. Long-term survival was estimated by Kaplan-Meier analysis. RESULTS: 2634 patients (68% men, mean age 60 years) were operated for aortic aneurysm (n=1821, 69%) or aortic dissection (n=813, 31%). Overall, increased age, aortic dissection, emergency operation, coronary artery bypass grafting, postoperative stroke, and postoperative renal failure were independently associated with surgical mortality. Only age was independently associated with long-term mortality. Later era of treatment (1998 2004 vs 1992-1997) was associated with lower risk only for aneurysm patients, despite similar changes in surgical approach. Long-term survival for all patients was 83% at 1 year, 77% at 5 years, and 73% at 10 years and identical for aneurysm and dissection when adjusted for surgical mortality. CONCLUSIONS: Increased age was associated with increased mortality across follow-up, implicating early surgery when possible. Results improved over time for aneurysms but not dissections; however, long-term survival was equal. PMID- 17336539 TI - Adapt or die The imperative for a culture of innovation in cardio-thoracic surgical training. PMID- 17336540 TI - Systemic venous drainage: can we help Newton? AB - In recent years substantial progress occurred in the techniques of cardiopulmonary bypass, but the factor potentially limiting the flexibility of cardiopulmonary bypass remains the drainage of the systemic venous return. In the daily clinical practice of cardiac surgery, the amount of systemic venous return on cardiopulmonary bypass is directly correlated with the amount of the pump flow. As a consequence, the pump flow is limited by the amount of venous return that the pump is receiving. On cardiopulmonary bypass the amount of venous drainage depends upon the central venous pressure, the height differential between patient and inlet of the venous line into the venous reservoir, and the resistance in the venous cannula(s) and circuit. The factors determining the venous return to be taken into consideration in cardiac surgery are the following: (a) characteristics of the individual patient; (b) type of planned surgical procedure; (c) type of venous cannula(s); (d) type of circuit for cardiopulmonary bypass; (e) strategy of cardiopulmonary bypass; (f) use of accessory mechanical systems to increased the systemic venous return. The careful pre-operative evaluation of all the elements affecting the systemic venous drainage, including the characteristics of the individual patient and the type of required surgical procedure, the choice of the best strategy of cardiopulmonary bypass, and the use of the most advanced materials and tools, can provide a systemic venous drainage substantially better than what it would be allowed by the simple "Law of universal gravitation" by Isaac Newton. PMID- 17336541 TI - Formoterol and beclomethasone dipropionate interact positively in antagonising bronchoconstriction and inflammation in the lung. AB - These studies were designed to assess the pharmacodynamic interaction between formoterol and beclomethasone dipropionate (BDP) in controlling the bronchoconstriction and inflammatory response induced by various challenges in guinea-pigs and rats. In anaesthetised guinea-pigs, superfusion of the formoterol/BDP combination into the tracheal lumen had significantly more effect than the single components in antagonising the bronchoconstricting and inflammatory responses to acetylcholine or ovalbumin in a standard model of airway hyper-responsiveness. After ovalbumin challenge, the combination completely protected animals from death at doses lower than those effective when given separately. The combination, at doses ineffective individually, even counteracted the development of lung oedema induced by sephadex in the rat. Finally, in tracheal strips from ovalbumin-sensitised guinea-pigs pre-treatment with BDP (30 mg kg(-1) i.m.) completely reversed the rightward shift of the formoterol dose-response curve due to beta(2)-receptor desensitisation. In conclusion, these results indicate that formoterol and BDP together induce a favourable pharmacodynamic interaction which can be considered more than additive, at least in these experimental settings. PMID- 17336542 TI - Green tea attenuates diabetes induced Maillard-type fluorescence and collagen cross-linking in the heart of streptozotocin diabetic rats. AB - The enhanced myocardial collagen content, collagen glycation and the resulting advanced glycation end products (AGE) which exhibit the characteristics of increased cross-linking are proposed for the stiffness of myocardium in diabetes. To explore the cardioprotective effect of green tea in diabetes, we study the effect of green tea extract on myocardial collagen characteristics in streptozotocin diabetic rats. The effect of green tea on marker enzymes in serum and cardiac tissues were also assayed to understand the extent of protection. Six weeks after the diabetes induction, diabetic rats were treated with green tea extract [300 mg (kg body weight)(-1)day(-1)] for 4 weeks. AGE were determined by fluorescence assay and cross-linking of collagen by solubility measurement while collagen content was measured by biochemical assay. The activities of aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatine kinase (CPK) were measured by biochemical assay. The increase in blood glucose, glycated hemoglobin and systolic blood pressure in diabetic rats were reduced upon green tea treatment. The activities of AST, LDH and CPK were significantly increased in serum whereas decreased in cardiac tissues in diabetic rats representing the cardiac damage. Administration of green tea to diabetic rats significantly ameliorates these enzyme activities. There was no significant difference in the myocardial collagen content among the experimental rats. A significant (P<0.05) increase in collagen linked Maillard-type fluorescence and decrease in collagen solubility in the myocardium of diabetic rats as compared to control rats (0.955+/-0.02 versus 0.683+/-0.04 and 30+/-1.41 versus 45.17+/-1.17, respectively) indicates the increase in advanced glycation end products formation and degree of collagen cross-linking. Green tea administration to diabetic rats significantly (P<0.05) decreased the fluorescence (0.73+/-0.02) whereas increased the solubility of collagen (41.5+/-1.04) indicating the reduction in advanced glycation end products and collagen cross-linking. The present study reveals that green tea by ameliorating myocardial collagen characteristics may provide a therapeutic option in the treatment of cardiovascular complications of diabetes. PMID- 17336543 TI - Radical induced fragmentation of amino acid esters using triphenylcorrole(CuIII) complexes. AB - A triphenylcorrole(CuIII) complex is covalently bound to amino acid esters at the nitrogen atom. As a result radical anions are generated, inducing the occurrence of side-chain reactions under CID conditions. Almost all of the amino acid esters that were studied show abundant ions that correspond to fragmentation at the alpha carbon either with or without the loss of the alkoxy ester moiety. Distinctive CID spectra were also recorded for leucine and isoleucine complexes. Initial results with short peptides are also shown. PMID- 17336544 TI - Mass analysis in islands of stability with linear quadrupoles with added octopole fields. AB - Mass analysis with linear quadrupole mass filters is possible by forming "islands" in the stability diagram with auxiliary quadrupole excitation. In this work, computer simulations are used to calculate stability boundaries, island positions, and peak shapes and ion transmission for mass analysis with linear quadrupole mass filters that have added octopole fields of about 2 to 4%. Rod sets with exact geometries that have quadrupole and octopole fields only in the potential, and round rod sets, with multipoles up to N = 10 (the twenty pole term) included in the calculations, show the same stability boundaries, island positions, and peak shapes. With the DC voltage applied to the rods so that the Mathieu parameter a < 0, conventional mass analysis is possible without the use of an island. With the DC polarity reversed so that a > 0, the resolution and transmission are poor preventing conventional mass analysis. In principle, mass analysis in an island is possible with operation at either of two tips. Provided the correct island tip is chosen for mass analysis, peak shapes comparable to those with a > 0 and no excitation are possible, both with a > 0 and with a < 0. In the latter case, the use of an island of stability allows mass analysis when the added octopole otherwise prevents conventional mass analysis. PMID- 17336545 TI - Viral recognition by Toll-like receptors. AB - Toll-like receptors (TLRs) have evolved to recognize conserved features of microbial pathogens, including bacteria, viruses, fungi, and protozoa. Among these pathogen classes, viruses are particularly vexing, as they generally lack any uniquely foreign features that easily distinguish them from the host. Consequently, a number of TLR family members have evolved to recognize various forms of viral nucleic acid. The emergence of this specificity has interesting implications for how we view the evolution of viral genomes. In this review, I discuss the various strategies used by TLRs to recognize viruses as well as the experimental evidence implicating TLRs in viral immunity. PMID- 17336546 TI - Persistence of improvements in postural strategies following motor control training in people with recurrent low back pain. AB - This study investigated long-term effects of training on postural control using the model of deficits in activation of transversus abdominis (TrA) in people with recurrent low back pain (LBP). Nine volunteers with LBP attended four sessions for assessment and/or training (initial, two weeks, four weeks and six months). Training of repeated isolated voluntary TrA contractions were performed at the initial and two-week session with feedback from real-time ultrasound imaging. Home program involved training twice daily for four weeks. Electromyographic activity (EMG) of trunk and deltoid muscles was recorded with surface and fine wire electrodes. Rapid arm movement and walking were performed at each session, and immediately after training on the first two sessions. Onset of trunk muscle activation relative to prime mover deltoid during arm movements, and the coefficient of variation (CV) of EMG during averaged gait cycle were calculated. Over four weeks of training, onset of TrA EMG was earlier during arm movements and CV of TrA EMG was reduced (consistent with more sustained EMG activity). Changes were retained at six months follow-up (p<0.05). These results show persistence of motor control changes following training and demonstrate that this training approach leads to motor learning of automatic postural control strategies. PMID- 17336547 TI - Mapping the spinal and supraspinal pathways of dynamic mechanical allodynia in the human trigeminal system using cardiac-gated fMRI. AB - Following injury and inflammation, pain to light stroking (dynamic mechanical allodynia) might develop at the damaged site (primary area) or in adjacent normal tissue (secondary area). Using fMRI we mapped changes in the spinal trigeminal nucleus (spV), and supraspinal brainstem nuclei following heat/capsaicin-induced primary and secondary dynamic mechanical allodynia in the human trigeminal system. The role of these structures in dynamic mechanical allodynia has not been clarified yet in humans. During the control session we applied the same mechanical stimuli to the same untreated trigeminal area. Primary and secondary mechanical allodynia showed equal levels of perceived pain intensity, and compared to control mechanical stimulation exhibited similar responses in the ipsilateral spV and contralateral ventrolateral periaqueductal gray (vlPAG). Activity in the spV was significantly higher during both conditions versus the control mechanical stimulation, indicating that central sensitization of second order neurons is similar for primary and secondary mechanical allodynia. The vlPAG showed decreased activity that inversely correlated with pain ratings during primary allodynia, i.e. the more deactivated the vlPAG the higher the pain intensity (p<0.05, Pearson's correlation). Primary and secondary dynamic mechanical allodynia were also characterized by significant differences involving distinct supraspinal structures mainly involved in pain modulation and including the rostroventromedial medulla, pons reticular formation, dorsolateral PAG, all more active during primary versus secondary allodynia, and the medial reticular formation of the caudal medulla that was more active during secondary versus primary allodynia. These results indicate that the pain modulatory system is involved to a different extent during primary versus secondary mechanical allodynia. PMID- 17336548 TI - The hemodynamic response of the alpha rhythm: an EEG/fMRI study. AB - EEG was recorded during fMRI scanning of 16 normal controls in resting condition with eyes closed. Time variations of the occipital alpha band amplitudes were correlated to the fMRI signal variations to obtain insight into the hemodynamic correlates of the EEG alpha activity. Contrary to earlier studies, no a priori assumptions were made on the expected shape of the alpha band response function (ARF). The ARF of different brain regions and subjects were explored and compared. It was found that: (1) the ARF of the thalamus is mainly positive. (2) The ARFs at the occipital and left and right parietal points are similar in amplitude and timing. (3) The peak time of the thalamus is a few seconds earlier than that of occipital and parietal cortex. (4) No systematic BOLD activity was found preceding the alpha band activity, although in the two subjects with the strongest alpha band power such correlation was present. (5) There is a strong and immediate positive correlation at the eyeball, and a strong negative correlation at the back of the eye. Furthermore, it was found that in one subject the cortical ARF was positive, contrary to the other subjects. Finally, a cluster analysis of the observed ARF, in combination with a Modulated Sine Model (MSM) fit to the estimated ARF, revealed that within the cortex the ARF peak time shows a spatial pattern that may be interpreted as a traveling wave. The spatial pattern of alpha band response function represents the combined effect of local differences in electrical alpha band activity and local differences in the hemodynamic response function (HRF) onto these electrical activities. To disentangle the contributions of both factors, more advanced integration of EEG inverse modeling and hemodynamic response modeling is required in future studies. PMID- 17336549 TI - Positron emission tomography with 18F-FDG in osteoarthritic knee. AB - OBJECTIVES: To evaluate osteoarthritis (OA) of the knee using positron emission tomography (PET) with 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) as a tracer. MATERIALS AND METHODS: Fifteen patients with medial-type knee OA and three healthy subjects were enrolled in the study. After clinical examination and conventional radiography, (18)F-FDG PET and magnetic resonance imaging (MRI) were performed. (18)F-FDG uptake was quantified as a standardized uptake value (SUV) and the localization of (18)F-FDG uptake was identified using fusion images created with MRI scans. RESULTS: (18)F-FDG generally accumulated in periarticular lesions and was absent in the articular cartilage. SUVs of the whole knee were higher in OA than in controls, and those in the medial condyle were higher than in the lateral condyle in OA. Prominent (18)F-FDG uptake was found in the intercondylar notch in OA and extended along the posterior cruciate ligament (PCL) in some cases. Periosteophytic accumulation was found in one-half of cases with definite osteophytes. Accumulation was also found in subchondral lesions and bone marrow, which corresponded with bone edema diagnosed by MRI. No significant correlation was found between SUV and clinical manifestations. CONCLUSIONS: (18)F FDG uptake was upregulated in OA and generally accumulated in periarticular lesions. Increased uptake was found in the intercondylar notch extending along the PCL, periosteophytic lesions, and bone marrow. These results provide in vivo pathognomonic insights into OA. PMID- 17336550 TI - Amoeba proteus displays a walking form of locomotion. AB - This report deals with observations on the directional locomotion of amoeba before and after fixation and scanning electron microscopy. The study was aimed at visualization of the stepwise events of directional movements. After the analysis of the data it is proposed that the amoeba undergoes a sequence of movement events that can be defined as a walking form of locomotion. PMID- 17336551 TI - Epidermal growth factor (EGF) receptor endocytosis is accompanied by reorganization of microtubule system in HeLa cells. AB - Translocation of endosomes along microtubules (MTs) from the cell periphery toward the juxtranuclear region proximal to MTOC is well established. During this translocation the radial MT system is believed to retain its organization. Here we demonstrate that epidermal growth factor receptor (EGFR) endocytosis in HeLa cells is accompanied by dramatic remodeling of the MT system. Synchronized endocytosis was stimulated by warming the cells after EGF prebinding to EGFR on ice. Soon after that MTs were fully reestablished and EGFR was found in EE aligned along peripheral MTs. By the beginning of EE-to-LE sorting, the number of long MTs decreased and MTs appeared like an entangled meshwork of disorientated fragments and were partially depolymerized. Simultaneously, tubulin staining increased in juxtranuclear region, and at the time of LE-Lys interaction, enlarged EGFR-containing endosomes were localized there. Radial MTs were re established when EGF-EGFR degradation started in lysosomes. In EGF absence, no alterations occurred upon MTs re-establishment. We conclude that MT remodeling is endocytosis-dependent. PMID- 17336552 TI - Antioxidant metabolism in Xenopus laevis embryos is affected by stratospheric balloon flight. AB - To test the effects of low levels of radiation from space on living organisms, we flew Xenopus laevis embryos at different stages of development on a stratospheric balloon (BI.R.BA mission). After recovery, different parameters were analyzed to assess the effects of flight, with particular regard to oxidative stress damage. Because of failed temperature control during flight, the flight shielded embryos (FC) could not be used for biochemical or morphological comparisons. In contrast, the incubation conditions (i.e. temperature, containers, volumes) for the flight embryos (F) were parallel to those for the ground controls. Mortality data show that younger embryos (16 h) flown on the balloon (F) are more sensitive to radiation exposure than older ones (40 h and 6 days). Exposure during flight lowered the antioxidant potential in all embryos, particularly older ones. These preliminary data demonstrate that flight on a stratospheric balloon might affect antioxidant metabolism, though it is not yet possible to correlate these results with low radiation exposure during flight. PMID- 17336553 TI - Synthesis of beta-alanine C60 derivative and its protective effect on hydrogen peroxide-induced apoptosis in rat pheochromocytoma cells. AB - Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities, especially prominent in neural diseases. One of the effective ways to prevent the reactive oxygen species (ROS) mediated cellular injury is dietary or pharmaceutical augmentation of some free radical scavenger. Water-soluble amino-fullerene derivative is a novel compound that behaves as a free radical scavenger with excellent biocompatibility. In the present study, we synthesized a novel beta-alanine C(60) derivative. The product was characterized by FT-IR, (1)H NMR, (13)C NMR, LC-MS and elemental analysis. We investigated the protective effect on hydrogen peroxide-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with hydrogen peroxide underwent apoptotic death determined by MTT, flow cytometry analysis and PI/Hoechst 33342 staining. Moreover, the scavenging ability of beta-alanine C(60) derivative to reactive oxygen species both in vivo and in vitro of PC12 cells was measured. The results suggest that beta-alanine C(60) derivative has the potential to prevent oxidative stress-induced cell death without evident toxicity. Hence, on the basis of the above-mentioned studies, we can hypothesize that the protective effect of beta-alanine C(60) derivative on H(2)O(2) induced apoptosis is related to their known scavenger activity toward ROS. PMID- 17336554 TI - The impact of post-learning sleep vs. wakefulness on recognition memory for faces with different facial expressions. AB - A beneficial effect of sleep after learning, compared to wakefulness, on memory formation has been shown in many studies using a variety of tasks. However, none of these studies has specifically addressed recognition memory for faces so far. The recognition of familiar faces, together with the extraction of emotional information from facial expression, is a fundamental cognitive skill in human everyday life, for which specific neural systems and mechanisms of processing have been developed. Here, we investigated the role of post-learning sleep for later recognition memory for neutral, happy, and angry faces. Twelve healthy subjects, after judging the emotional valence of the faces in the evening (learning phase), either slept normally in the subsequent night, with sleep recorded polysomnographically (sleep condition), or remained awake (wake condition) according to a cross-over design. Recognition testing took place in the second evening after learning, i.e. after a further night of regular sleep spent at home. Sleep after learning, compared to wakefulness, enhanced memory accuracy in recognition memory. This effect was independent of the emotional valence of facial expression. The response criterion at recognition testing did not differ between sleep and wake conditions. The amount of non rapid eye movement (NonREM) sleep during post-learning sleep correlated positively with memory accuracy at recognition testing, while time in REM sleep was associated with a speeded responding to the learned faces. Results suggest that face recognition, despite its dependence on specialized brain systems, nevertheless relies on the general neural mechanisms of sleep-associated memory consolidation. PMID- 17336555 TI - Embolisation of symptomatic pelvic veins in women presenting with non-saphenous varicose veins of pelvic origin - three-year follow-up. AB - AIM: To evaluate the clinical results of embolisation of symptomatic, incompetent pelvic veins in women presenting with perineal veins. PATIENTS AND METHODS: Twenty-four women presenting with non-saphenous perineal varicose veins and who experienced pelvic vein syndrome were treated. Symptoms was scored on a visual analogue scale assessing dyspareunia, pelvic and lower limb pain. Lower limb varices were investigated by duplex ultrasonography. Pelvic veins were studied by pelvic vein angiography with simultaneous embolisation of incompetent veins. Ovarian and internal iliac veins were systematically embolised when incompetent. Follow-up assessment of symptoms and varices was carried out at 1, 2 and 3 years. RESULTS: All patients presented with perineal veins, 2 with sciatic vein incompetence and 2 with a perforator of the thigh or buttock. Pelvic venous angiography was performed via right femoral access in 87% of the cases and confirmed the presence of incompetent ovarian and internal iliac veins. The mean number of coils used per vein was 6 and all were successfully embolised. No serious complications were encountered. The mean clinical improvement score was 80%, 77%, 80% and 76% at respectively 45 days, 1, 2 and 3-year follow-up. CONCLUSION: In women of reproductive age, non-saphenous varicose veins associated with pelvic venous incompetence (PVI) should undergo pelvic vein investigation. In this clinical series we achieved a satisfactory improvement in symptoms after 3 years following treatment of incompetent pelvic veins. PMID- 17336556 TI - Analyses, extensions and comparison of three experimental schemes for measuring ((n)J(CH)+D(CH))-couplings at natural abundance. AB - Three types of experiments for measuring (n)J(CH) heteronuclear long-range coupling constants are examined and extended with state-of-the-art pulse sequence building-blocks: The use of a HMBC with corresponding reference-HSQC for accurate coupling determination is combined with the constant time technique and the conversion of antiphase magnetization into ZQ/DQ-coherences; CPMG-based LR-CAHSQC and BIRD(r,X)-HSQMBC experiments are examined in detail with respect to their coherence transfer properties; finally, the HSQC-TOCSY-IPAP experiment is introduced, a sequence derived from previously published alpha and beta selective HSQC-TOCSYs using a different spin state selection technique and a recently developed ZQ-suppression method. The experiments are characterized with their advantages and disadvantages and compared using strychnine and menthol as standard molecules. PMID- 17336557 TI - Effects of tenotomy on patients with infantile nystagmus syndrome: foveation improvement over a broadened visual field. PMID- 17336558 TI - Cough, pain and dyspnoea: similarities and differences. AB - The three common symptoms, pain, dyspnoea and cough, share some important features. We felt that the analogies to be made among them could be instructive, possibly suggesting new avenues of research. Each of these symptoms can be profoundly uncomfortable, and can profoundly degrade quality of life. The sign, cough, is often given more prominence than the symptom, urge to cough, but both are important to the patient (the former may be of more concern to nearby people). Advances in pain research over the last several decades have pointed the way to new studies of dyspnoea; they may serve as a model for the psychophysical study of the perception of urge to cough, as well as providing models for understanding both central and peripheral sensitization of the afferent pathway. We briefly review here the afferent and central pathways and psychophysics of pain, dyspnoea and urge to cough. PMID- 17336559 TI - The accumulation and synthesis of betaine in winter skate (Leucoraja ocellata). AB - The present study investigated aspects of betaine metabolism in an elasmobranch fish, the winter skate (Leucoraja ocellata). Based on the level of choline dehydrogenase (ChoDH) activity, the liver and kidney appear to be the major sites of betaine synthesis and the mitochondrial localization of ChoDH and betaine aldehyde dehydrogenase (BADH) indicates that the metabolic organization of betaine synthesis in winter skate is similar to other vertebrates. Food deprivation did not affect white muscle betaine content, and prolonged starvation (70 days) appeared to decrease the total hepatic betaine synthetic capacity. There was no decrease in ChoDH or BADH activity at the mitochondrial level with starvation, suggesting any decrease is due to catabolism of hepatic reserves rather than downregulation of betaine synthesis. Skates fed a high betaine diet (frozen squid approximately 55 micromol g(-1)) had elevated white muscle betaine content compared to those fed a low betaine diet (frozen herring <2 micromol g( 1)); however, high dietary betaine intake did not affect the activity of betaine synthesizing enzymes in liver. Acclimation to elevated salinity (120 and 130% seawater) did not result in an increase in white muscle betaine content. Taken as a whole, the present data suggest that diet is a major determinant of muscle betaine in the winter skate and that betaine is of marginal importance as an intracellular osmolyte in this species. PMID- 17336560 TI - Cloning and expression analysis of myogenin from flounder (Paralichthys olivaceus) and promoter analysis of muscle-specific expression. AB - Myogenin is a bHLH transcription factor of the MyoD family. It plays a crucial role in myoblast differentiation and maturation. We report here the isolation of flounder myogenin gene and the characterization of its expression patterns. Sequence analysis indicated that flounder myogenin shared a similar structure and the conserved bHLH domain with other vertebrate myogenin genes. Flounder myogenin gene contains 3 exons and 2 introns. Sequence alignment and phylogenetic showed that flounder myogenin was more homologous with halibut (Hippoglossus hippoglossus) myogenin and striped bass (Morone saxatilis) myogenin. Whole-mount embryo in situ hybridization revealed that flounder myogenin was first detected in the medial region of somites that give rise to slow muscles, and expanded later to the lateral region of the somite that become fast muscles. The levels of myogenin transcripts dropped significantly in matured somites at the trunk region. Its expression could only be detected in the caudal somites, which was consistent with the timing of somite maturation. Transient expression analysis showed that the 546 bp flounder myogenin promoter was sufficient to direct muscle specific GFP expression in zebrafish embryos. PMID- 17336561 TI - Factors and markers of growth hormone secretion and gonadal function in Fanconi anemia. AB - Many factors may be involved in the growth and gonadal dysfunction of Fanconi anemia (FA). OBJECTIVE: To evaluate the (1) relationship between FA presentation, including genital abnormalities and pituitary stalk interruption syndrome (PSIS), (2) markers of growth hormone (GH) deficiency and gonadal function, and (3) factors influencing final height and gonadal function. PATIENTS: Twenty five patients with FA were included, 17 of them were given bone marrow transplantation. RESULTS: Six patients were diagnosed with GH deficiency and PSIS (group A), whereas 19 had no evidence of GH deficiency (group B). In group A, all patients had more than 3 FA malformations and all 5 boys had cryptorchidism associated with microphallus in 4. All patients had heights and plasma insulin like growth factor I < -3SD. Final height was reached in 15 patients and was < or = -2SD in 12 of them, all but 3 were born small for gestational age and/or given norethandrolone and/or corticosteroids. Gonadal function was abnormal in 5/7 boys and 4/5 girls evaluated at pubertal age. The plasma concentrations were low in 4/9 for antimullerian hormone and in 3/9 for inhibin B, 3 of them had been given bone marrow transplantation. CONCLUSIONS: PSIS can be part of a severe FA phenotype. It seems to occur mainly in boys, with more than 3 malformations, microphallus and cryptorchidism. This phenotype is associated with normal blood counts, defining a new clinical subgroup of patients. PMID- 17336562 TI - The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with Mucopolysaccharidosis Type I. AB - A global, observational disease registry has been established to characterize the course of disease and track clinical outcomes in patients with Mucopolysaccharidosis Type I (MPS I), a rare and treatable lysosomal storage disorder. This report outlines procedures for data collection and presents the recommended minimum schedule of assessments that comprise the disease-specific clinical and laboratory parameters that are tracked in the database. Aggregate data are summarized for the first 302 patients enrolled, representing entries from 24 countries. The median current age of the patients is 9.0 years (range: 0.4-64.8). Syndrome diagnoses include 47% Hurler (severe form), 25% Hurler-Scheie (attenuated form with an intermediate phenotype), 13% Scheie (most attenuated form), and 15% unknown. Younger ages at symptom onset and disease diagnosis are associated with the severe Hurler syndrome, but there is overlap among syndromes. Diagnosis was delayed by years to decades in several patients with Hurler-Scheie and Scheie syndromes. Patients with symptom onset before age 5 are more likely to have a gibbus, cognitive impairment, and pneumonia, whereas patients with symptom onset above age 5 are more likely to have carpal tunnel syndrome, myelopathy, and glaucoma. Cardiac valve abnormalities, joint contractures, corneal clouding, and hernia are reported by over 70% of patients regardless of the age of symptom onset. Approximately 80% of the patients have received enzyme replacement therapy, hematopoietic stem cell transplantation, or both. Overall, the MPS I Registry database contains a broad sample of the global patient population, providing a potentially useful tool for expanding knowledge of MPS I and facilitating evidence-based decisions about the optimal means of monitoring and treating affected individuals. PMID- 17336563 TI - Characterization and pharmacokinetic study of recombinant human N acetylgalactosamine-6-sulfate sulfatase. AB - Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The aims of this study were to establish Chinese hamster ovary (CHO) cells overexpressing recombinant human GALNS (rhGALNS) and to assess pharmacokinetics and tissue distribution of purified enzymes by using MPS IVA knock-out mouse (Galns(-/-)). The CHO-cell derived rhGALNS was purified from the media by a two-step affinity chromatography procedure. The rhGALNS was administered intravenously to 3-month old Galns(-/-) mice at a single dose of 250U/g of body weight. The treated mice were examined by assaying the GALNS activity at baseline and up to 240min to assess clearance of the enzyme from blood circulation. The mice were sacrificed 4h after infusion of the enzyme to study the enzyme distribution in tissues. The rhGALNS was purified 1317-fold with 71% yield. The enzyme was taken up by Galns( /-) chondrocytes (150U/mg/15h). The uptake was inhibited by mannose-6-phosphate. The enzyme activity disappeared from circulation with a half-life of 2.9min. After enzyme infusion, the enzyme was taken up and detected in multiple tissues (40.7% of total infused enzymes in liver). Twenty-four hours after a single infusion of the fluorescence-labeled enzymes into MPS IVA mice, biodistribution pattern showed the amount of tagged enzyme retained in bone, bone marrow, liver, spleen, kidney, and heart. In conclusion, we have shown that the phosphorylated rhGALNS is delivered to multiple tissues, including bone, and that it functions bioactively in Galns(-/-) chondrocytes implying a potential enzyme replacement treatment. PMID- 17336564 TI - Variation and expression of dihydrofolate reductase (DHFR) in relation to spina bifida. AB - The dihydrofolate reductase (DHFR) enzyme is important for folate availability, folate turnover and DNA synthesis. The 19-bp deletion in intron-1 of DHFR has been associated with the risk of having spina bifida affected offspring, supposedly by changing DHFR gene expression. A 9-bp repeat in exon 1 of the mutS homolog 3 (MSH3) gene was recently demonstrated to be also located in the 5'UTR of DHFR and may possibly affect DHFR gene expression as well. We examined the association between these DHFR variants and spina bifida risk and investigated their effect on DHFR expression. Our study population, consisting of 121 mothers of a spina bifida affected child, 109 spina bifida patients, 292 control women and 234 pediatric controls was screened for the DHFR 19-bp deletion and the DHFR 9-bp repeat. DHFR gene expression was measured in 66 spina bifida patients, using real-time PCR analysis. In this study population, the DHFR 19-bp del/del genotype was not associated with spina bifida risk in mothers and children (OR: 0.8; 95%CI: 0.4-1.5 and OR: 1.2; 95%CI: 0.6-2.2, respectively) and both the WT/del and the del/del genotype did not affect DHFR expression relative to the WT/WT genotype (relative expression=0.89, p=0.46 and relative expression=1.26, p=0.24, respectively). The DHFR 9-bp repeat was not associated with spina bifida risk in mothers and children. DHFR expression of the 6/6 allele was 73% increased compared to the 3/3 allele, although not significantly (relative expression=1.73, p=0.09). We did not find evidence for an effect of the DHFR 19-bp deletion or 9 bp repeat on spina bifida risk in mothers and children. An effect of the 6/6 repeat genotype on DHFR expression cannot be ruled out. PMID- 17336565 TI - DNA methylation status is not impaired in treated cystathionine beta-synthase (CBS) deficient patients. AB - BACKGROUND: Cystathionine beta-synthase (CBS) deficiency is an inborn error of metabolism that is biochemically characterized by severe hyperhomocysteinemia and homocystinuria. In tissues of mice deficient for CBS it has been demonstrated that global DNA methylation and DNA methylation of the H19 differentially methylated region (DMR) were impaired. In this study we aimed to investigate whether DNA methylation is disturbed in patients with hyperhomocysteinemia due to CBS-deficiency. METHODS: Genomic DNA was isolated from heparin blood from nine CBS deficient patients that were treated with homomcysteine-lowering therapy and eight healthy controls. Global DNA methylation was measured by liquid chromatography-electrospay ionization-tandem mass spectrometry and gene-specific DNA methylation of the H19 DMR was determined by bisulphite-sequencing. RESULTS: Homocysteine, AdoMet and AdoHcy levels were significantly elevated, whereas no differences in AdoMet:AdoHcy ratio were observed in plasma of treated CBS deficient patients compared with controls. Global DNA methylation and gene specific DNA methylation of the H19 DMR was not different between CBS deficient patients and controls. CONCLUSION: We demonstrate that DNA methylation is not impaired in treated CBS deficient patients. Further studies are necessary to investigate the precise role of homocysteine-lowering therapy in relation to DNA methylation in patients with homocystinuria. PMID- 17336566 TI - Association between gastric acid suppressants and Clostridium difficile colitis and community-acquired pneumonia: analysis using pharmacovigilance tools. AB - OBJECTIVE: Recent epidemiological studies identifying an association between some classes of gastric acid suppressants and Clostridium difficile colitis and community-acquired pneumonia prompted our analysis. Our objective was to retrospectively apply data mining algorithms (DMAs) to the Food and Drug Administration (FDA) drug safety database to see if they might have directed/redirected attention to the reported association of gastric acid suppressive drugs with C. difficile colitis and community-acquired pneumonia, prior to the published epidemiological findings that supported the association. DESIGN: Two statistical DMAs, proportional reporting ratios (PRRs) and multi-item gamma Poisson shrinker (MGPS), were applied to a spontaneous reporting system (SRS) database to identify signals of disproportionate reporting (SDRs). RESULTS: SDRs related to community-acquired pneumonia were observed for two proton pump inhibitors (lansoprazole and omeprazole), two H2 antagonists (famotidine and roxatidine), and one antacid (magnesium silicate hydroxide). For C. difficile colitis, an SDR was generated for one proton pump inhibitor (lansoprazole). CONCLUSIONS: Although our analysis suggests that there may be an association between the SDRs using SRS data and the epidemiological findings, these results may not have alerted public health professionals in advance of published studies to an association between proton pump inhibitors/gastric acid suppressants and C. difficile colitis or community-acquired pneumonia. However, the analysis reveals the potential utility of DMAs to direct attention to more subtle indirect drug adverse effects in SRS databases that as yet are often identified from epidemiological investigations. PMID- 17336567 TI - Invasive aspergillosis associated with bevacizumab, a vascular endothelial growth factor inhibitor. PMID- 17336568 TI - MSG1, a surface-localised protein of Mycoplasma suis is involved in the adhesion to erythrocytes. AB - Mycoplasma suis is a member of the group of uncultivable haemoplasmas which colonise erythrocytes of a wide range of vertebrates. Adhesion to erythrocytes is the crucial step in the unique haemoplasma life cycle. Due to the lack of a cultivation system, no adhesion structures have been identified so far. In order to determine potential adhesion molecules of M. suis, we screened genomic M. suis libraries. The protein MSG1 with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) similarity was identified. The encoding gene msg1 is 1011bp in size. The overall homology of the deduced amino acid sequence to GAPDHs of other pathogenic mycoplasmas ranged from 52.6% to 54.5%. Recombinant MSG1 expressed in Escherichia coli exhibited GAPDH activity. Immunoblot and immunoelectron microscopy analyses using antibodies against rMSG1 verified the membrane and surface localisation of native MSG1 in M. suis. Furthermore, we showed that rMSG1 binds to erythrocyte lysate in a dose-dependent manner. E. coli transformants which express MSG1 on their surface acquire the ability to adhere to porcine erythrocytes. This adhesion could be specifically and significantly inhibited by rMSG1 and antibodies to MSG1. In conclusion, our studies indicate that the membrane associated MSG1 represents the first putative adhesion protein identified in the group of haemoplasmas. PMID- 17336569 TI - Aberrant life cycle of human immunodeficiency virus type 1 CRF15_01B-like clinical isolates from Thailand in human CD4+ T-cell lines. AB - Human immunodeficiency virus type 1 (HIV-1) is separated into several subtypes and circulating recombinant forms (CRFs). Here, infections of 4 clinical isolates (0-47-1, CU98-26, CU98-28, and CU98-31) from Thailand were examined in human CD4(+) T-cell lines, MT-4 and MOLT-4. The CU98-26 isolates in both cells and 0-47 1 in MT-4 established chronic infections, as in control 2 subtype B isolates from Japan, while 0-47-1 in MOLT-4 caused a latent infection. In contrast, CU98-28 and CU98-31 established aberrant infections in both cells. Integrated provirus was detected in all the chronic infections, including 0-47-1 in both cells. In contrast, extrachromosomal circular forms of HIV-1 DNA were detected in CU98-28- and CU98-31-infected cells, whereas the amount of the integrated form was below the limit of detection. Interestingly, phylogenetic trees and sequencing revealed that all the Thai isolates, except 0-47-1, displayed CRF15_01B-like mosaic structures of CRF01_AE with subtype B-like sequences in several regions that were apparently different from those of the inocula in peripheral blood mononuclear cells. Thus, in the infections of most of the above Thai isolates it was suggested that a minor population with mosaic patterns having multiple breakpoints between CRF01_AE and subtype B in the inocula could be selected by the T-cell lines. PMID- 17336570 TI - Iliopsoas hematoma in patients with hemophilia: a single-center study. AB - Six cases of iliopsoas hematoma were diagnosed in 5 patients with hemophilia over the last 5 years at our hemophilia center. We reviewed these cases to determine the incidence and precipitating factors of iliopsoas hematoma in hemophilia. Of the 5 patients, 4 had severe hemophilia A and 1 had moderate hemophilia A with a history of inhibitors to factor VIII concentrates. The age range was 13 to 33 years. The hematoma was posttraumatic in 2 cases and spontaneous in 4 cases. Femoral nerve compression developed in 2 cases. There were four recurrences. At the time of the hematoma, 2 patients were receiving long-term prophylactic factor VIII concentrate therapy but one of them had stopped the injections of his own accord. The treatment consisted of recombinant factor VIII concentrates, a brief course of glucocorticoid therapy in the 2 cases with femoral nerve involvement, lower limb traction in 3 patients, and rehabilitation therapy. The annual incidence rate of iliopsoas hematoma was 2.9/1000 patients with severe or moderate hemophilia A. The use of prophylactic factor VIII therapy and compliance with recommendations about avoiding activities that put strain on the hip flexor muscles probably explain the low rate of iliopsoas muscle hematoma in patients with hemophilia in France. An early diagnosis allows early Factor VIII therapy, which decreases the risk of femoral nerve involvement and recurrence. PMID- 17336571 TI - Lymph node paradoxical enlargement during treatment for tuberculous spondylodiscitis (Pott's disease). AB - INTRODUCTION: Paradoxical reactions during adapted antituberculous treatment are defined as a transient, clinical and/or radiological enlargement of pre-existent lesions or appearance of new ones. OBSERVATION: We report herein the case of a 62 year-old woman who suffered under treatment of Pott's disease from an enlargement of her para-vertebral abscess and disco-vertebral lesions, and a tuberculous paradoxical reaction characterized by the development of uni- then bilateral cervical lymph nodes. Outcome was favourable after drainage by percutaneous punction of the adenopathies and oral short course of corticosteroids, and the continuation of combined antituberculous therapy. CONCLUSION: Paradoxical reactions under adapted antituberculous treatment must be considered only after excluding an inadequate or irregular intake, or absorption of antituberculous drugs. This phenomenon is not rare, and has been reported even in ten to 15% of the patients not infected with the human immunodeficiency virus. The adjunction of a short course of corticosteroids may be necessary and rapidly efficient to control these reactions, in combination with surgical or percutaneous drainage of the enlarged lymph nodes, to avoid unfavourable and/or unaesthetic fistulisations. PMID- 17336572 TI - [Ultrasonography of fetal esophagus: healthy appearance and prenatal diagnosis of a case of esophagus atresia with esotracheal fistula]. AB - The thoracic part of a fetal esophagus is generally overlooked by usual prenatal ultrasonography. However, screening it might improve the detection rate of esophageal malformations for which prenatal diagnosis remains far from accurate. In this article, we describe the technique which makes it possible to get a precise image of a fetal thoracic esophagus in its more sensitive part: between the trachea and the aorta. After describing the appearance of a healthy thoracic esophagus, we will show how this technique can be used for prenatal detection of esophagus malformations. For this purpose, we provide the case report of a prenatal diagnosis of esophagus atresia with esotracheal fistula. PMID- 17336573 TI - Facile sonochemical synthesis of nanosized InP and GaP. AB - A novel sonochemical method for the preparation of MP (M=Ga, In) nanocrystalline materials has been developed. The procedure consists of the in situ synthesis of sodium phosphide and its subsequent reaction with the appropriate metal chloride using ultrasound. The products were characterized by X-ray powder diffraction, electron microscopy, and energy dispersive X-ray microanalysis (EDX). The choice of solvent and the use of high-power ultrasound are both important in the formation of the products. PMID- 17336574 TI - Comparison of simultaneous continuous intracranial pressure (ICP) signals from ICP sensors placed within the brain parenchyma and the epidural space. AB - Simultaneous continuous intracranial pressure (ICP) signals from two different ICP sensors (Codman ICP MicroSensor; Johnson & Johnson, Raynham, MA) placed within the brain parenchyma and the epidural space were compared in ten patients with idiopathic normal pressure hydrocephalus (iNPH). Comparisons were made at the single ICP wave level by determining differences in mean pressure, and pulse pressure amplitude (dP) and latency (dT, i.e. rise time). Differences for the parameters mean ICP, mean ICP wave amplitude and mean ICP wave latency were also determined during consecutive 6-s time windows. The ICP sensors located within the brain parenchyma and epidural space showed marked differences in mean pressure. On the contrary, there were minor differences between sensors in 8 of 10 patients regarding single wave pulse pressure amplitude (dP) and single wave latency (dT, i.e. rise time), and also with regard to the parameters mean ICP wave amplitude and mean ICP wave latency. The levels of mean ICP wave amplitudes used for predicting shunt response in iNPH patients were independent of sensor location in 9 of 10 patients. These results extend previous data that epidural ICP monitoring cannot be used to reliably determine mean ICP, however, epidural ICP monitoring is very useful for determining ICP waveform parameters such as pulse pressure amplitude (dP) and mean ICP wave amplitude. It is suggested that epidural ICP monitoring with determination of mean ICP wave amplitude can be used to predict shunt response in iNPH, though an ICP sensor designed for epidural ICP monitoring would be preferable. PMID- 17336575 TI - Regulation of nuclear receptor and coactivator functions by the carboxyl terminus of ubiquitin-conjugating enzyme 9. AB - Small ubiquitin-related modifier (SUMO) is a protein moiety that is ligated to lysine residues in a variety of target proteins. The SUMO E2 enzyme ubiquitin conjugating enzyme 9 (Ubc9) is sufficient for substrate recognition and lysine modification of known SUMO targets. Previous studies have demonstrated that mutated Ubc9 that has lost its SUMO-ligating activity retains its enhancement on transactivation mediated by androgen receptor (AR). In contrast to the binding ability to Ubc9, the sumoylation of AR via the association of SUMO-1 and PIAS1 is able to repress AR-dependent transcription. In the present study, we present several lines of evidence to explain the role of over-expressed Ubc9 as a cofactor in the nuclear receptor and coactivator functions, including (i) activity that is independent of its ability to catalyze SUMO-1 conjugation, (ii) an insight into the protein-protein interaction motif in its eight C-terminal residues, (iii) selective coactivator function in nuclear receptor-relevant transactivation activities, and (iv) a non-trichostatin A-sensitive autonomous transcription repression domain in its far C-terminal region. Taken together, our data suggest that the both the protein-protein interaction through the Ubc9 C terminus and its sumoylation-modifying activity provide the mechanism for regulating nuclear receptor functions. PMID- 17336576 TI - Biochemical and biophysical characterization of small heat shock proteins from sugarcane. Involvement of a specific region located at the N-terminus with substrate specificity. AB - When cells are submitted to an increase in temperature, heat shock proteins (Hsp) are synthesized to help heat stress resistance. Small Hsps, which are diverse and abundant in plants, have the major function of preventing irreversible protein aggregation. The diversity of small Hsps in plants is intriguing and characterization of their chaperone activity is important to understand plant tolerance to heat stress. A previous study showed that small Hsps, mainly represented by class I (cytosolic), correspond to about 5% of all sugarcane Expressed Sequencing Tags belonging to the molecular chaperone category. Here, we present biochemical and biophysical characterization of two sugarcane small Hsps from class I, which were named SsHsp17.2 and SsHsp17.9 according to their monomer molecular mass of 17.2 and 17.9 kDa, respectively. The recombinant proteins have identity of about 75% to each other and similar structural characteristics. However, their stability and their chaperone activity were not equivalent: SsHsp17.9 was more efficient in protecting citrate synthase and malate dehydrogenase from aggregation whereas SsHsp17.2 was more efficient in protecting luciferase from aggregation. There is only one region, which is located at the N terminus, of low homology between these two proteins. Based on that and on previous works pointing to multiple sites, mainly at the N-terminus, involved with substrate specificity in small Hsps, we suggest that this specific region is one of these sites. In addition, this is the first report on the chaperone activity of sugarcane small Hsps. PMID- 17336577 TI - Glucocorticoids in the regulation of transcription factors that control cytokine synthesis. AB - The interaction at different levels between intracellular signals elicited by cytokines and activated glucocorticoid receptors (GR) is essential for the regulation of immune responses. We describe different levels of interaction between glucocorticoids and cytokines which result in the induction or repression of gene transcription. These include the regulation of cytokine receptor expression, the molecular cross-talk between the GR and transcription factors (TFs) activated by cytokine signaling, the interaction with several signaling pathways and also posttranslational modifications of both GR and TFs. Also, an overview of the implications of chromatin remodeling in this interplay is discussed. The complexity of the intricate network involved in the interaction between GR and TFs is pivotal for the final outcome of cytokines biological action. PMID- 17336578 TI - Cytokines coming of age in South America. PMID- 17336579 TI - Cytokines and chemokines shaping the B-cell compartment. AB - The whole life of a B-cell from a stem cell to a mature plasma cell is governed, among other factors, by cytokines and growth factors in their microenvironment. Remarkable progress in the understanding of the mechanisms of cytokines action on the B-cell compartment was achieved by analysis of gene-targeted mice. The generation of mice deficient for individual cytokines or their receptors has shed light on the in vivo function of cytokines in B-cell responses. This review focuses on the role of cytokines in the development, maturation and differentiation of different B-cell subsets into antibody-secreting cells or memory B-cells. PMID- 17336580 TI - Study of the organic residue from a 2600-year old Etruscan plumpekanne. AB - Excavation of the Etruscan Necropolis dell'Osteria near Vulci (VI Century b.c.) brought to light in Tomb 2 a bronze plumpekanne. According to preliminary X-ray observation, an unusually thick deposit of organic nature lay at its bottom. Numerous samples of the residue were investigated using microFTIR and diffuse reflectance FTIR spectroscopy. For comparative purposes similar analyses were performed on samples of resins mentioned in classical sources. Spectroscopic results identify the residue as mastic or incense, both triterpenic resins. The former seems to be preferred since, according to classical sources, it was used as must additive. PMID- 17336581 TI - Calibration in non-linear NIR spectroscopy using principal component artificial neural networks. AB - Near-infrared (NIR) spectroscopy was used in simultaneous, non-destructive analysis of antipyriine and caffeine citrate tablets. Principal component artificial neural networks (PC-ANNs) were used to construct models for the analytes, using the testing set for external validation. Four pretreated spectra, namely, first-derivative, second-derivative, standard normal variate (SNV) and multiplicative scatter correction (MSC) spectra led to simplified and more robust models than conventional spectra. In PC-ANNs models, the spectra data were analyzed by principal component analysis (PCA) firstly. Then the scores of the principal compounds (PCs) were chosen as input nodes for input layer instead of the spectra data. The artificial neural networks (ANNs) models using the spectra data as input nodes were also established, which were compared with the PC-ANNs models. The result shows the SNV model of PC-ANNs multivariate calibration has the lowest training error and predicting error. The concept of the degree of approximation was introduced and performed as the selective criterion of the optimum network parameters. PMID- 17336582 TI - The hydrogen bonding and amino-imino tautomerization of the alkoxy-aminopyridines and amino-methoxypyrimidines with acetic acid The effects of the methoxy group. AB - The hydrogen bonding and amino-imino tautomerization of the systems of 2-amino-3 methoxypyridine (2A3MOP), 2-amino-6-methoxypyridine (2A6MOP), 2-amino-6-n propoxypyridine (2A6NPOP), 2-amino-6-iso-propoxypyridine(2A6IPOP), 2-amino-4 methoxypyrimidine (2A4MOPM), 4-amino-2-methoxypyrimidine (4A2OPM), 4-amino-6 methoxypyrimidine (4A6MOPM), 2-amino-4-methoxy-6-methylpyrimidine (MMPM), and 2 amino-4,6-dimethoxypyrimidine (DMOPM), with acetic acid (AcOH) in n-hexane at room temperature were investigated by means of the UV absorption and fluorescence spectroscopy. From the UV absorption spectra the presence of the dual hydrogen bonded complexes that linked by a 1:1 molar ratio with AcOH were found, since the enthalpy changes accompanying the hydrogen bond formation between 2A3MOP, 2A4MOPM, 4A2MOPM, 4A6MOPM, or MMPM, and AcOH were ca. 42.8-61.1kJmol(-1) in n hexane. The fluorescence spectra of the 2A3MOP/AcOH, 2A4MOPM/AcOH, 4A6MOPM/AcOH, and MMPM/ AcOH systems revealed that the imino-tautomers were produced through double proton transfer in the amino hydrogen-bonded 1:1 complexes in the S1 state, but the imino-tautomer formation for the 4A2MOPM/AcOH system was not found on account of the steric hindrance due to the inversion of the methoxy group in the S1 state. The imino-tautomer for the MMPM/AcOH system fluoresces most intensely among these systems investigated. On the other hand, not only the formation of the corresponding amino dual hydrogen-bonded complex and but also that of imino-tautomer were prevented for the 2A6MOP/AcOH, 2A6NPOPM/AcOH, 2A6IPOP/AcOH, and DMOPM/AcOH systems, because of the steric hindrance of the methoxy group in both the S0 and S1 states. The theoretical approaches by an ab initio molecular orbital calculation were in accord with the experimental results. PMID- 17336583 TI - Carbon monoxide exposure in households in Ciudad Juarez, Mexico. AB - This study assessed exposure to carbon monoxide from gas and wood heater emissions in a sample of 64 households in peri-urban residential areas in Ciudad Juarez, Chihuahua, Mexico. Indoor and outdoor carbon monoxide concentrations and temperatures were monitored for a continuous period of 1 week at 1 and 6-min intervals, respectively. The moving average carbon monoxide concentrations were compared to the World Health Organization (WHO) standards for carbon monoxide. Sixty-seven percent of households with gas heaters and 60% of households with wood heaters exceeded a health-based standard at some point during the monitoring. The difference between indoor and outdoor temperatures was modestly correlated with average carbon monoxide exposure (r=0.35, p-value <0.01). Heater type may be a stronger determinant of exposure, as households with a particular heater model (the El Sol FM-210) were significantly more likely to be among the more highly exposed households (odds ratio of 4.8, p-value of 0.02). A variety of health effects were pooled and found at elevated frequency in the households that exceeded the 8-h standard of 9ppm (odds ratio=5.1, p-value=0.031). These results highlight the need for further efforts to identify and mitigate potentially hazardous carbon monoxide exposures, particularly in moderate-income countries with cooler climates. PMID- 17336584 TI - No air leak on PPV does not exclude tracheobronchial injury after blunt chest trauma. AB - Tracheobronchial injuries are commonly associated with persistent air leak with pneumothoraces especially when on positive pressure ventilation (PPV). Injuries with absence of these features together with collapse of the lung and consequent low arterial oxygen tension while on PPV are less well recognised. We present a patient with traumatic aortic dissection and preoperatively undiagnosed complete transaction of the left main bronchus following blunt chest trauma. He had no persistent air leak with lower lung lobe collapse despite undergoing PPV and had low arterial oxygen tension which failed to respond to appropriate oxygen therapy. PMID- 17336585 TI - Acute pulmonary thromboembolism during mitral valve repair. AB - Perioperative pulmonary thromboembolism during cardiac surgery is extremely rare. We report a 55-year-old male, who developed acute pulmonary thromboembolism during mitral valve repair. Intra-operative trans oesophageal echocardiography failed to demonstrate thromboembolus in the pulmonary arteries but it showed the secondary signs of acute pulmonary artery obstruction. Thromboembolectomy was done after high index of suspicion on clinical grounds was found and the patient recovered. The diagnostic accuracy and sensitivity of transoesophageal echocardiography in circumstances with altered haemodynamics is questionable and has not been investigated. Therefore, indirect evidence of pulmonary artery obstruction on echocardiography may have a predictive value and failure to demonstrate pulmonary thromboembolism by this tool should not exclude the possibility of it especially when it is highly suspected. PMID- 17336586 TI - Lung cancer masquerading as prosthetic valve endocarditis. AB - Although marantic endocarditis secondary to pulmonary adenocarcinoma is well described, it is very unusual for this symptom to be the initial presenting feature of lung cancer. Here we describe such a case in which marantic endocarditis affected not only the patient's native mitral valve, but also his newly implanted bioprosthetic valve--a phenomenon that has not been previously reported. PMID- 17336587 TI - Successful surgical treatment of protein-losing enteropathy complicating rheumatic tricuspid regurgitation. AB - Protein-losing enteropathy may uncommonly complicate cardiac disease. While well described as a complication for patients having undergone previous Fontan surgery for congenital heart disease, pericardial and valvular aetiologies are much less frequent. We report a 35-year-old female presenting with marked hypoalbuminaemia and peripheral oedema on a background of known rheumatic valvular heart disease. After extensive investigation for gastrointestinal, hepatic and renal causes of protein loss, echocardiography demonstrated severe tricuspid valve incompetence. Subsequent invasive testing confirmed severe tricuspid valve regurgitation in the absence of pericardial constriction. The patient proceeded to tricuspid valve repair with resolution of the protein-losing state and correction of hypoalbuminaemia. While cardiac causes of gastrointestinal protein loss are uncommon, they should be considered when initial diagnostic work up is negative. The importance of correction of haemodynamic precipitants of protein-losing enteropathy is also discussed. PMID- 17336588 TI - Perinatal group B streptococcal disease. AB - Group B streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis. Despite optimal treatment of GBS-infected neonates it is associated with significant morbidity and mortality, and prevention strategies are required. As disease occurs rapidly, and is often evident at birth or within 12 hours of birth, antibiotics must be given prior to delivery, and when administered early enough, and at the correct doses, they will prevent the majority of early-onset GBS cases. Prevention is therefore in the hands of obstetricians and midwives. Women at higher risk of delivering infected infants can be identified through one of two strategies: the presence of one or more clinical risk factors, or the presence of GBS on lower vaginal/rectal swabs obtained late in pregnancy. Decisions on which strategy to use will depend on a number of factors. A swab based approach appears to have higher efficacy but is likely to lead to more antibiotic exposure. PMID- 17336589 TI - Effects of surgery on ischaemic mitral regurgitation: a prospective multicentre registry (SIMRAM registry). AB - AIMS: Functional ischaemic mitral regurgitation (IMR) is common in patients with ischaemic left ventricular dysfunction undergoing coronary artery bypass surgery. Although the presence of IMR negatively affects prognosis, the additional benefit of valve repair is debated, particularly with mild IMR at rest. Exercise echocardiography may help identify a subset of patients at higher risk of cardiovascular events by revealing the dynamic component of IMR. METHODS: A large prospective, multicentre, non-randomized registry is designed to evaluate the effects of surgery on IMR at rest and on its dynamic component at exercise (z). SIMRAM will enrol approximately 550 patients with IMR in up to 17 centres with clinical and exercise follow-up for 1 year. Three sets of outcomes will be prospectively assessed and several hypotheses will be tested including determinants of adverse outcome and progressive left ventricular remodeling, efficacy of treatment and role of ischaemia on the dynamic consequences of IMR. Enrolment began in November 2006 and is expected to end by early 2008. PMID- 17336590 TI - A pilot study of fecal serine-protease activity: a pathophysiologic factor in diarrhea-predominant irritable bowel syndrome. AB - BACKGROUND & AIMS: The pathogenesis of irritable bowel syndrome (IBS) remains only partially understood, and no specific or universally effective patient management procedure has been developed to date. Our study was designed to evaluate if colonic luminal serine-proteases may be a relevant pathophysiologic marker of IBS. METHODS: Fecal samples of 38 IBS patients, 15 patients with ulcerative colitis (UC), and 15 healthy controls were studied. Fecal serine protease activity was determined photometrically by using azocasein as a proteolytic substrate; fecal pancreatic elastase-1 and mast cell tryptase content were measured by enzyme-linked immunosorbent assay. Fecal secretory leukocyte protease inhibitor concentration was determined by enzyme-linked immunosorbent assay in control subjects and in patients with diarrhea-predominant IBS. RESULTS: Fecal serine-protease activity was 3-fold higher in patients with diarrhea predominant IBS than in both controls and IBS patients with either constipation or alternating bowel habits. Fecal serine-protease activity was not correlated with the frequency of bowel movements in all groups. Increased serine-protease activity also was detected in stools of UC patients. No significant difference was observed in the fecal mast cell tryptase and pancreatic elastase concentrations between all groups, or in the fecal secretory leukocyte protease inhibitor concentration between controls and diarrhea-predominant IBS patients. CONCLUSIONS: Fecal serine-protease activity is increased markedly in patients with diarrhea-predominant IBS. This increase, however, is not coupled with changes in either mast cell tryptase or pancreatic elastase concentrations. Thus, serine-protease activity in the colon may be a pathophysiologic factor in the development of diarrhea-predominant IBS. PMID- 17336591 TI - Neutrophil recruitment and barrier impairment in celiac disease: a genomic study. AB - BACKGROUND & AIMS: Celiac disease is an enteropathy featuring villous atrophy, crypt hyperplasia, and lymphocytosis. Tissue remodeling is driven by an inflammatory reaction to gluten in genetically susceptible individuals. The adaptive pathway is considered the major immune response but recent evidence has indicated the involvement of innate immunity as well. To assess the contribution of either immune response we performed global gene expression profiling of the regenerating mucosa. METHODS: Microarray hybridizations were performed with biopsy samples from 13 untreated patients, 31 patients on a gluten-free diet in various stages of remission, and 21 controls. Additional data were generated using low-density array and conventional quantitative reverse-transcription polymerase chain reaction, and immunohistochemistry. RESULTS: A total of 108 differentially expressed immune-related genes were identified (50 innate, 43 adaptive, 9 both innate/adaptive, and 6 immunoregulatory). Expression levels showed a gradual change as opposed to the discrete histological transitions. In addition to details provided on the adaptive and innate immune pathways used, we observed a chronic recruitment of activated neutrophils. Neutrophil involvement was unabated in otherwise completely normalized remission patients. CONCLUSIONS: We observed a contribution of both the innate and adaptive immune response in celiac disease pathogenesis. The discrepancy between the histological classification and the observed incremental change in immune-gene expression may have consequences for current diagnostic inclusion criteria. Enhanced neutrophil infiltration in both active and remission patients points to a genetic impairment of the intestinal barrier that may contribute to the cause rather than the consequence of celiac disease. PMID- 17336593 TI - Endoscopic ultrasound-guided fine-needle aspiration of ascites. AB - BACKGROUND & AIMS: The aim of this study is to report a large single-center experience with endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of ascites. METHODS: Consecutive patients at our institution in whom EUS-guided paracentesis was performed between January 1997 and July 2005 were identified retrospectively. All procedures were performed by or under the supervision of 1 of 5 experienced endosonographers with available on-site cytopathology. RESULTS: Sixty consecutive patients (33 men; mean age, 67 y) were identified. Previously attempted percutaneous paracentesis was unsuccessful in 3 of 6 patients. Ascites confirmed by EUS FNA was visible in 28 of 54 (52%) computerized tomography, 3 of 11 (27%) transabdominal ultrasound, and 4 of 8 (50%) magnetic resonance imaging examinations before EUS. Transgastric (n = 55) or transduodenal (n = 5) EUS guided paracentesis (mean, 8.9; range, 1-40 mL) revealed malignancy in 16 (27%) from primary pancreatic (n = 9), gastric (n = 2), urothelial (n = 1), esophageal (n = 1), gallbladder (n = 1), bile duct (n = 1) cancer, and lymphoma (n = 1). The cytology from 2 patients was atypical (1 suspicious for malignancy and 1 considered reactive) and the remaining 42 were benign. Potential complications occurred in 2 of 60 (3%) patients with self-limited fever. Of the 8 of 60 (13%) patients who underwent subsequent surgery, 3 had metastatic pancreatic adenocarcinoma (n = 2) and metastatic small intestinal carcinoid (n = 1) to the peritoneum after negative EUS-FNA cytology. CONCLUSIONS: EUS frequently identifies ascites missed by other imaging studies. EUS-guided paracentesis may identify malignancy in a subset of patients. Negative ascitic fluid cytology from EUS FNA does not exclude possible peritoneal carcinomatosis. PMID- 17336592 TI - What to do when you suspect gastrointestinal lymphoma: a pathologist's perspective. AB - Although primary gastrointestinal (GI) lymphomas are an infrequent occurrence and represent 1%-4% of the malignant tumors of the GI tract, secondary involvement of the GI tract by lymphoma is not uncommon. Several controversies remain about the prognostic stratification and the optimal treatment modalities for these lymphomas. A crucial component of answering these questions is an accurate and complete characterization of the tumor. The currently used World Health Organization classification of hematologic malignancies requires integration of morphologic, immunophenotypic, and genotypic features to define a disease type. Through the use of a representative case we highlight how this information is used for the appropriate diagnosis of a GI lymphoma. We also discuss the clinical features, including radiologic and endoscopic findings in patients presenting with a GI lymphoma. The review is a pathologist's perspective on what to do when suspecting a lymphoma of the GI tract. PMID- 17336594 TI - Manganese superoxide dismutase dimorphism and iron overload, hepatocellular carcinoma, and death in hepatitis C virus-infected patients. AB - BACKGROUND & AIMS: A genetic dimorphism encodes for either alanine (Ala) or valine (Val) in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD), and modulates its mitochondrial import and activity. It has been shown that the presence of at least 1 Ala-encoding allele is more frequent in alcoholic patients with cirrhosis than in controls, and increases the risks of liver iron overload, hepatocellular carcinoma (HCC), and death in these patients. The aim of this study was to assess the influence of the Ala-9Val MnSOD dimorphism on the same parameters and events in hepatitis C virus (HCV)-infected patients. METHODS: We compared the MnSOD genotypic distributions in 94 control subjects and 165 patients with HCV-related cirrhosis. Patients were included at the time of liver biopsy examination showing cirrhosis, and were followed-up prospectively. The mean time of follow-up evaluation was 85.7 +/- 43.8 months. RESULTS: The distribution of MnSOD genotypes in HCV-infected patients (25% Val/Val homozygotes, 44% Ala/Val heterozygotes, and 31% Ala/Ala homozygotes) did not differ from the distribution in controls (P = .3). MnSOD genotypes did not influence survival (log-rank test, P = .6; relative risk 1.0; 95% confidence interval, 0.6-1.6) or the risk of HCC occurrence (log-rank test, P = .3; relative risk, 1.1; 95% confidence interval, 0.8-1.6). CONCLUSIONS: Contrary to previous findings in French alcoholic patients, the Ala-encoding MnSOD allele is represented equally in controls and patients with HCV-related cirrhosis, and it does not significantly influence the risks of liver iron overload, HCC, or death in these patients. PMID- 17336595 TI - Autonomic nervous system and secretion across the intestinal mucosal surface. AB - Chloride secretion is important because it is the driving force for fluid movement into the intestinal lumen. The flow of accumulated fluid flushes out invading micro-organisms in defense of the host. Chloride secretion is regulated by neurons in the submucosal plexus of the enteric nervous system. Mechanosensitive enterochromaffin cells that release 5-hydroxytryptamine (5-HT) and activate intrinsic afferent neurons in the submucosal plexus and initiate chloride secretion. Mechanical stimulation by distention may also trigger reflexes by a direct action on intrinsic afferent neurons. Dysregulation of 5-HT release or altered activity of intrinsic afferents is likely to occur in states of inflammation and other disorders. PMID- 17336596 TI - Analysis of DNA repair and recombination responses in mouse cells depleted for Brca2 by SiRNA. AB - The tumor suppressor BRCA2 is considered to play an important role in the maintenance of genome integrity through the repair of DNA lesions by homologous recombination. A mechanistic understanding of BRCA2 has been complicated by the embryonic lethality of mice bearing allelic knockouts of Brca2, and by variation in the DNA damage response in cells bearing BRCA2 deficiencies. It would be advantageous to develop approaches that avoid the cell lethality associated with complete inactivation of the gene, or the use of established tumor cell lines in which other genes in addition to BRCA2 may be mutant. In this study, SiRNA was used in stable transformation assays to knockdown Brca2 in mouse hybridoma cells by at least 75%. The Brca2-depleted cells were analyzed with respect to cell growth, sensitivity to DNA damaging agents (mitomycin C, methylmethane sulfonate, or ionizing radiation), intrachromosomal homologous recombination and gene targeting. Although the effect of Brca2-depletion on cell growth and sensitivity to DNA damaging agents was modest, the Brca2-depleted cells did show a significant shift in homologous recombination from gene conversion to single strand annealing and a significant decrease in the efficiency of gene targeting. Both of these phenotypes are consistent with the proposed role of Brca2 in DNA repair and recombination. PMID- 17336597 TI - Frequency of cytokine gene promoter polymorphisms in the Northern Ireland cystic fibrosis population. AB - It has been postulated that cytokine allele frequencies are gender and perhaps geographically-specific. Cytokine release is crucial in the regulation of the type and magnitude of the immune response. This study observed no differences in the frequency of cytokine promoter polymorphisms associated with variant levels of expression in patients with CF and a non-CF population of Northern Ireland. PMID- 17336598 TI - The cerebellar fastigial nucleus contributes to CO2-H+ ventilatory sensitivity in awake goats. AB - The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is an important determinant of CO(2)-H(+) sensitivity during wakefulness. Bilateral, stainless steel microtubules were implanted into the CFN (N=9) for injection (0.5-10 microl) of the neurotoxin ibotenic acid. Two or more weeks after implantation of the microtubules, eupneic breathing and CO(2) H(+) sensitivity did not differ significantly (P>0.10) from pre-implantation conditions. Injection of ibotenic acid (50 mM) did not significantly alter eupneic Pa(CO2) (P>0.10). The coefficient of variation of eupneic Pa(CO2) was 4.0+/-0.6 and 3.7+/-0.4% over the 2 weeks before and after the lesion, respectively. CO(2)-H(+) sensitivity expressed as inspired ventilation/Pa(CO2) decreased from 2.15+/-0.17 pre-lesion to 1.58+/-0.26 l/(min mmHg) 3-6 days post lesion (P<0.02, -27%). There was no significant (P>0.10) recovery of sensitivity between 7 and 10 days post-lesion. The lesion also increased (P<0.05) the day-to day variability of this index by nearly 100%. When CO(2) sensitivity was expressed as elevated inspired CO(2)/room air V (I), values at 7%, but not 3 and 5% inspired CO(2), were reduced and more variable (P<0.05) after the ibotenic acid injections. We conclude that during wakefulness, the CFN contributes relatively more to overall ventilatory drive at high relative to low levels of hypercapnia. PMID- 17336599 TI - Changes in glucose do not alter baseline firing rate or chemosensitivity of serotonin neurons cultured from the medullary raphe. AB - A subset of serotonin neurons are putative central respiratory chemoreceptors. To test the hypothesis that serotonin neurons also have intrinsic glucose sensitivity, perforated patch recordings were made from cultured rat medullary raphe neurons after pharmacological blockade of fast glutamatergic and GABAergic synaptic transmission. It has previously been shown that all neurons stimulated by acidosis under these conditions are tryptophan hydroxylase (TPH) immunoreactive. Changes in glucose concentration from 0.1 to 20 mM had no effect on baseline firing rate of 31 neurons that were stimulated by hypercapnic acidosis. The response to hypercapnic acidosis of 25 of these neurons was the same in 0.1, 1, 2, 5 and/or 20 mM glucose as it was in 10 mM glucose. Changes in glucose also did not alter the baseline firing rate of 13 neurons that did not respond to acidosis. Although it is possible that these results were influenced by the use of tissue culture, they do not provide support for intrinsic glucose sensitivity of pH-sensitive serotonin neurons of the medullary raphe. PMID- 17336600 TI - Electric synapses in the carotid body-nerve complex. AB - Slices of rat carotid bodies, or cultured glomus cells, were used to study intercellular coupling. This phenomenon occurs because gap junctions allow passage of currents and dyes from one cell to another. There is a two-way resistive coupling between glomus cells (GC/GC coupling), which is accompanied by activity of intercellular channels. Coupling between glomus cells and nerve endings is more complex. Coupling is mostly resistive from cell to nerve (GC/NE) but it is mostly capacitive in the opposite direction (NE/GC). Thus, slow electric events originating in the glomus cells can be transferred to the nerve endings. But, only electric transients can pass from nerve to cell. There is also coupling between nerve endings (NE/NE), which is mostly capacitive in either direction. Chemoreceptor stimulants (acute and chronic hypoxia, hypercapnia, acidity, cholinergic agents and dopamine) uncouple most glomus cells, accompanied by cell depolarization and decreased amplitude of junction channels. Chronic hypobaric hypoxia increases GC/NE, NE/GC and NE/NE coupling. GC/GC uncoupling seems related to transmitter secretion. Transmission across chemical synapses is aided by increased coupling from glomus cell to nerve ending. PMID- 17336601 TI - Effective separation and simultaneous determination of seven fluoroquinolones by capillary electrophoresis with diode-array detector. AB - A simple, rapid and accurate method has been developed for effective separation and simultaneous determination of lomefloxacin, gatifloxacin, enoxacin, ciprofloxacin, ofloxacin, enrofloxacin and pefloxacin residues in porcine tissue by capillary electrophoresis with diode-array detector. The separation conditions were investigated and optimized. The sample was extracted with acetonitrile, and a mixture consisted of 25 mM NaH(2)PO(4), 25 mM Na(2)B(4)O(7) and 25 mM H(3)BO(3) (pH 9.0) was used as a running buffer. A linear relationship between concentration and peak area for each compound was obtained in the concentration range of 0.5-100 mg/L with a correlation coefficient greater than 0.9994. For analysis of porcine tissue, the detection limits of lomefloxacin, gatifloxacin, enoxacin, ciprofloxacin, ofloxacin, enrofloxacin and pefloxacin were 0.013, 0.012, 0.023, 0.040, 0.037, 0.035 and 0.034 mg/kg, respectively. The recoveries are in the range of 72-93%. The intra-day precision is less than 5%, and the inter-day precision is less than 10%. The proposed method has high resolution, speed and the extremely small sample volume required. It can permit to confirm the presence of the studied seven fluoroquinolones in porcine tissue at the required maximum residue limit (MRL) level. PMID- 17336602 TI - Stable isotope dilution analysis of salicylic acid and hydroquinone in human skin samples by gas chromatography with mass spectrometric detection. AB - A sensitive and accurate gas chromatographic-mass spectrometric (GC-MS) method has been developed for the quantitative determination of salicylic acid (SA) and hydroquinone (HQ) from human skin samples and cosmetic emulsions. Deuterium labeled SA-d(6) and HQ-d(6) were used as internal standards (IS). The samples were extracted with methanol, dried under nitrogen and derivatized with N,O bis(trimethylsilyl)trifluoroacetamide (BSTFA)+1% trimethylchlorosilane (TMCS). Quantification was performed in SIM mode with a limit of quantification (LOQ) of 50 ng ml(-1) for SA and 10 ng ml(-1) for HQ. The inter-day variation (R.S.D.) was less than 5% and the accuracy was better than 13.3% for both compounds. The recoveries from the different matrices ranged between 93.1 and 103.3% for SA, and 97.3 and 100.8% for HQ. PMID- 17336603 TI - Serum protein profile of rheumatoid arthritis treated with anti-TNF therapy (infliximab). AB - We analyzed the changes in the serum protein profile by infliximab using two dimensional gel electrophoresis and mass spectrometry. More than 50 gel spots were seen to increase or decrease in correlation with clinical improvements of RA. The spots corresponding to CRP, C3, and Apo J showed reduced staining intensity, while the spots corresponding to Apo A-I, RBP, and transthyretin were enhanced. The protein profile of RA patients treated with infliximab was mostly similar to that of normal healthy controls except for several protein spots. This suggested that infliximab normalized the serum protein profile of RA patients, leading to modification in the serum lipid profile and antioxidant status in RA. PMID- 17336604 TI - Ultrasound in the diagnosis of steatosis and fibrosis of chronic liver diseases. PMID- 17336605 TI - Chromosomal anomalies in the aetiology of oesophageal atresia and tracheo oesophageal fistula. AB - Oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF) are severe congenital anomalies of which the aetiology is largely unknown. Several chromosomal anomalies have been described in patients presenting with these anatomical malformations, but until now none of these has led to the identification of a single aetiological factor. This paper reviews the chromosomal abnormalities reported in cases of OA/TOF and serves as a starting point to identify chromosomal regions harbouring genes involved in the aetiology of OA/TOF. PMID- 17336606 TI - Student psychiatric nurses' approval of containment measures: relationship to perception of aggression and attitudes to personality disorder. AB - Difficult and challenging behaviour by inpatients is a feature of acute psychiatric ward life. Different methods are used to contain these behaviours, and there is international variation in which are approved of or used. Previous research suggests that staff attitudes to patients may affect their willingness to use, or choice of, method. The aim of this study was to explore the relationship between approval of containment measures, perception of aggression and attitude to personality disorder. A survey of student psychiatric nurses was conducted, and using three attitudinal questionnaires related to aggression and containment. An association was found between positive attitude to patients and the approval of containment methods that involved nurses being in personal contact with patients. There was evidence that students' attitudes to patients deteriorated over time. The results highlighted the importance of (and linkage between) staffs' feelings of anger and fear towards patients, and their preparedness to use containment measures. PMID- 17336608 TI - Signal transducer and activator of transcription signals in allergic disease. AB - Signal transducer and activator of transcription (STAT) proteins are a group of transcription factors that transmit signals from the extracellular milieu of cells to the nucleus. They are crucial for the signaling of many cytokines that are mediators of allergic inflammation and impact various cell types critical to allergy including epithelial cells, mast cells, lymphocytes, dendritic cells, and eosinophils. Dysregulation of STAT signaling has been implicated in allergic disease, highlighting the importance of these ubiquitous molecules in allergic inflammation and the potential of these pathways as a target for therapeutic intervention. This review will summarize the current understanding of the roles of STAT signaling in allergic disease and the potential of targeting STATs for the treatment of allergic disorders, emphasizing recent observations. PMID- 17336609 TI - Proximal signaling events in Fc epsilon RI-mediated mast cell activation. AB - Mast cells are central mediators of allergic diseases. Their involvement in allergic reactions is largely dependent on activation through the specific receptor for IgE (Fc epsilon RI). Cross-linking of Fc epsilon RI on mast cells initiates a cascade of signaling events that eventually results in degranulation, cytokine/chemokine production, and leukotriene release, contributing to allergic symptomology. Because of the importance of IgE in allergy, much focus has been placed on deciphering the signaling events that take place downstream of Fc epsilon RI. Studies have identified spleen tyrosine kinase as a key proximal regulator of Fc epsilon RI-mediated signaling. In this review, we discuss the multiple pathways that diverge from spleen tyrosine kinase with emphasis on the role of adapter molecules to orchestrate these signaling events. Understanding the molecular mechanisms underlying mast cell activation ideally will provide insights into the development of novel therapeutics to control allergic disease. PMID- 17336610 TI - Severe intermittent wheezing in preschool children: a distinct phenotype. AB - BACKGROUND: Young children with wheezing predominantly with respiratory tract illnesses experience severe exacerbations separated by extended periods of wellness and may be described as having "severe intermittent wheezing," a diagnostic category not currently recognized in national guidelines. OBJECTIVE: We sought to characterize a cohort of children with recurrent severe wheezing. METHODS: A total of 238 children 12 to 59 months enrolled in the Acute Intervention Management Strategies trial were characterized through comprehensive allergy, asthma, environmental, and quality of life assessments. RESULTS: Asthma symptoms over the period of the preceding year occurred at frequencies consistent with intermittent asthma, as 94.5% of children experienced activity limitation < or = 2 times per month. However, frequent severe exacerbations were common, because 71% experienced > or = 4 wheezing episodes over the period of the preceding year, 95% made at least 1 primary care visit, 52% missed school or daycare, 40% made an emergency department visit, and 8% were hospitalized for wheezing illnesses. Atopic features were common, including eczema (37%), aeroallergen sensitization (46.8%), and positive asthma predictive index (59.7%). Oral corticosteroid use in the previous year (59.7% of the cohort) identified a subgroup with more severe disease documented by a higher incidence of urgent care visits (P = .0048), hospitalizations (P = .0061), aeroallergen sensitization (P = .047), and positive asthma predictive indices (P = .007). CONCLUSION: Among preschool children enrolled in the Acute Intervention Management Strategies trial, a subgroup was identified with severe intermittent wheezing characterized by atopic features and substantial illness-related symptom burden despite prolonged periods of wellness. CLINICAL IMPLICATIONS: Preschool children with recurrent severe wheezing episodes experience significant illness-related morbidity and exhibit features of atopic predisposition. PMID- 17336611 TI - Safety of leukotriene receptor antagonists in pregnancy. AB - BACKGROUND: Asthma is a chronic disorder that affects about 8% of pregnant women and may complicate pregnancy. Adequate asthma therapy in pregnancy is crucial but challenging because of safety concerns for the fetus. OBJECTIVE: To evaluate the safety of gestational asthma therapy with leukotriene receptor antagonists (LTRAs) for the mother and fetus/newborn. METHODS: Subjects were participants of the Organization of Teratology Information Specialists Asthma Medications in Pregnancy Study. Perinatal outcomes among 96 women who took LTRAs (montelukast or zafirlukast) were compared with women who exclusively took short-acting beta(2) agonists (n = 122) and women without asthma (n = 346). RESULTS: Use of LTRAs was not associated with an increased risk of pregnancy loss, gestational diabetes, preeclampsia, low maternal weight gain, preterm delivery, low Apgar scores, or reduced measures of birth length and head circumference in infants (P > .05). Slightly decreased birth weight in infants born to LTRA users could be attributed to maternal asthma severity/control. The birth prevalence of major structural defects in the LTRA group (5.95%) was significantly higher compared with controls without asthma (P = .007), but not different from the comparison group with asthma (P = .524). Furthermore, the defects observed in the LTRA group did not represent a consistent pattern. CONCLUSIONS: Use of LTRAs in pregnancy was not associated with a specific pattern of major structural anomalies in offspring or a large risk of other adverse perinatal outcomes. CLINICAL IMPLICATIONS: This study suggests that LTRAs do not appear to be a major human teratogen; however, results should be interpreted with caution because of limited sample size. PMID- 17336612 TI - Relationship between spleen tyrosine kinase and phosphatidylinositol 5' phosphatase expression and secretion from human basophils in the general population. AB - BACKGROUND: Previous studies have suggested that expression levels of spleen tyrosine kinase (syk) or phosphatidylinositol 5' phosphatase (SHIP) may explain certain extreme human basophil phenotypes. OBJECTIVE: This study is designed to explore whether variability in syk and SHIP expression levels in the general population, alone or in concert, can account for the variability in basophil function. METHODS: A survey of maximum responsiveness to IgE-mediated stimulation, sensitivity, and expression levels of 6 early signaling elements was performed on 36 subjects' basophils. RESULTS: Of the 6 signaling elements, only syk and SHIP showed a correlation with maximum histamine release or cellular sensitivity. In a multiple regression, syk and SHIP together could account for 67% of population variance, although most of the variance was explained by syk expression. The pattern of expression variance syk>>SHIP1>SHIP2 approximately lyn approximately p85 approximately cbl suggested a process that primarily modulated syk levels. IL-3 is known to modulate syk levels, but we found that a 3-day incubation with IL-3 resulted in increased expression of other signaling elements to a greater degree: cbl>SHIP1>SHIP2 approximately lyn approximately p85 > or = syk, opposite the pattern in the population survey. In contrast, 18-hour stimulation with anti-IgE antibody led to marked downregulation of syk expression, modest downregulation of Fc epsilon RI expression, weak downregulation of lyn expression, and no effect on 23 other signaling elements. CONCLUSION: Unlike studies in mice, we conclude that expression of syk is a good preconditioning predictor of basophil function in the general population. CLINICAL IMPLICATIONS: The finding that expression of syk levels may strongly influence functional responses of basophils suggests a mechanism underlying the severity of atopic diseases. PMID- 17336613 TI - Cat IgA, representative of new carbohydrate cross-reactive allergens. AB - BACKGROUND: Allergens from cat are among the most potent elicitors of allergic disease. Four cat allergens have been identified; however, evidence indicates the existence of additional allergens. OBJECTIVE: In this study, we evaluated IgE sensitization to IgA from cat. METHODS: Sera from cat-sensitized patients (n = 81) were analyzed for IgE antibodies to purified cat IgA in the Pharmacia CAP System. Indirect ELISA was performed with cat IgA, cat IgM, and deglycosylated cat IgA. Competitive inhibition ELISA was performed with cat IgA, cat IgM, calf intestine alkaline phosphatase (CIP), and cat serum albumin on solid phase bound cat IgA. IgE reactivity was also evaluated on membrane blotted cat IgA. RESULTS: Thirty-eight percent (31/81) of the cat-sensitized sera were ImmunoCAP-positive to cat IgA. Indirect ELISA demonstrated a high correlation between IgE reactivity to cat IgA and cat IgM (r = 0.94; P < .001). Very low responses were observed to deglycosylated IgA. Strong inhibition of cat IgA was observed in all sera after preincubation with cat IgA and cat IgM. Inhibition was also observed in most sera after preincubation with CIP. Immunoblotting demonstrated that the IgE reactivity was mainly directed to the heavy chain of IgA. CONCLUSION: This study has revealed a new allergen, cat IgA, containing a novel group of cross-reactive epitopes depending on carbohydrates also present on IgM and partially on CIP. CLINICAL IMPLICATIONS: This new group of cross-reactive carbohydrate IgE epitopes should be taken into consideration when diagnosing patients with suspected animal allergy. PMID- 17336614 TI - Inhibiting pollen reduced nicotinamide adenine dinucleotide phosphate oxidase induced signal by intrapulmonary administration of antioxidants blocks allergic airway inflammation. AB - BACKGROUND: Ragweed extract (RWE) contains NADPH oxidases that induce oxidative stress in the airways independent of adaptive immunity (signal 1) and augment antigen (signal 2)-induced allergic airway inflammation. OBJECTIVE: To test whether inhibiting signal 1 by administering antioxidants inhibits allergic airway inflammation in mice. METHODS: The ability of ascorbic acid (AA), N-acetyl cystenine (NAC), and tocopherol to scavenge pollen NADPH oxidase-generated reactive oxygen species (ROS) was measured. These antioxidants were administered locally to inhibit signal 1 in the airways of RWE-sensitized mice. Recruitment of inflammatory cells, mucin production, calcium-activated chloride channel 3, IL-4, and IL-13 mRNA expression was quantified in the lungs. RESULTS: Antioxidants inhibited ROS generation by pollen NADPH oxidases and intracellular ROS generation in cultured epithelial cells. AA in combination with NAC or Tocopherol decreased RWE-induced ROS levels in cultured bronchial epithelial cells. Coadministration of antioxidants with RWE challenge inhibited 4-hydroxynonenal adduct formation, upregulation of Clca3 and IL-4 in lungs, mucin production, recruitment of eosinophils, and total inflammatory cells into the airways. Administration of antioxidants with a second RWE challenge also inhibited airway inflammation. However, administration of AA+NAC 4 or 24 hours after RWE challenge failed to inhibit allergic inflammation. CONCLUSION: Signal 1 plays a proinflammatory role during repeated exposure to pollen extract. We propose that inhibiting signal 1 by increasing antioxidant potential in the airways may be a novel therapeutic strategy to attenuate pollen-induced allergic airway inflammation. CLINICAL IMPLICATIONS: Administration of antioxidants in the airways may constitute a novel therapeutic strategy to prevent pollen induced allergic airway inflammation. PMID- 17336615 TI - Sensitization to Ascaris lumbricoides and severity of childhood asthma in Costa Rica. AB - BACKGROUND: Little is known about sensitization (defined as a positive IgE) to helminths and disease severity in patients with asthma. OBJECTIVES: To examine the relationship between sensitization (defined as a positive IgE) to Ascaris lumbricoides and measures of asthma morbidity and severity in a Costa Rican population with low prevalence of parasitic infection but high prevalence of parasitic exposure. METHODS: Cross-sectional study of 439 children (ages 6 to 14 years) with asthma. Linear regression and logistic regression were used for the multivariate statistical analysis. RESULTS: After adjustment for parental education and other covariates, sensitization to Ascaris lumbricoides was associated with having at least 1 positive skin test to allergens (odds ratio, 5.15; 95% CI, 2.36-11.21; P < .001), increased total serum IgE and eosinophils in peripheral blood, reductions in FEV(1) and FEV(1)/forced vital capacity, increased airway responsiveness and bronchodilator responsiveness, and hospitalizations for asthma in the previous year (odds ratio, 3.08; 95% CI, 1.23 7.68; P = .02). CONCLUSION: Sensitization to Ascaris lumbricoides is associated with increased severity and morbidity of asthma among children in Costa Rica. This association is likely mediated by an increased degree of atopy among children with asthma who are sensitized to Ascaris. CLINICAL IMPLICATIONS: In areas with a low prevalence of helminthiasis such as Costa Rica, Ascaris sensitization may be an important marker of severe atopy and disease morbidity in children with asthma. PMID- 17336616 TI - T-bet inhibits both TH2 cell-mediated eosinophil recruitment and TH17 cell mediated neutrophil recruitment into the airways. AB - BACKGROUND: Previous studies have shown that mice lacking T-bet, a critical transcription factor for T(H)1 cell differentiation, spontaneously develop airway inflammation with intense eosinophil infiltrates. However, the mechanism underlying T-bet-mediated inhibition of allergic airway inflammation is still unknown. OBJECTIVE: To determine the regulatory role of T-bet in antigen-induced allergic airway inflammation. METHODS: We examined the role of T-bet in antigen induced allergic airway inflammation using T-bet(-/-) mice on a BALB/c background that did not develop spontaneous airway inflammation. We also examined the role of T-bet expression of CD4(+) T cells in airway inflammation by adoptive transfer experiments. RESULTS: We found that antigen-induced eosinophil recruitment, goblet cell hyperplasia, and T(H)2 cytokine production in the airways were enhanced in T-bet(-/-) mice. However, in the absence of signal transducer and activator of transcription 6 (STAT6), T-bet deficiency could not induce the antigen-induced eosinophilic airway inflammation. Adoptive transfer of T-bet(-/-) or T-bet(+/+) CD4(+) T cells to T-bet(-/-)Rag-2(-/-) mice revealed that the expression of T-bet in CD4(+) T cells was vital for the inhibition of antigen induced eosinophilic airway inflammation. Interestingly, antigen-induced neutrophil recruitment in the airways was also enhanced in T-bet(-/-) mice. Moreover, T-bet(-/-) CD4(+) T cells preferentially differentiated into IL-17 producing cells that mediated neutrophilic airway inflammation. CONCLUSION: T-bet inhibits both T(H)2 cell-mediated eosinophilic inflammation and T(H)17 cell mediated neutrophilic inflammation in the airways. CLINICAL IMPLICATIONS: The dysfunction of T-bet may be involved in the pathogenesis of severe asthma, in which accumulation of neutrophils as well as eosinophils in the airways is a hallmark of disease. PMID- 17336617 TI - Skin inflammation in RelB(-/-) mice leads to defective immunity and impaired clearance of vaccinia virus. AB - BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disorder occurring in genetically predisposed individuals with a systemic T(H)2 bias. Atopic dermatitis patients exposed to the smallpox vaccine, vaccinia virus (VV), occasionally develop eczema vaccinatum (EV), an overwhelming and potentially lethal systemic infection with VV. OBJECTIVE: To establish a murine model of EV and examine the effects of skin inflammation on VV immunity. METHODS: The skin of RelB(-/-) mice, like that of chronic AD lesions in humans, exhibits thickening, eosinophilic infiltration, hyperkeratosis, and acanthosis. RelB(-/-) and wild-type (WT) control mice were infected with VV via skin scarification. Viral spread, cytokine levels, IgG2a responses and VV-specific T cells were measured. RESULTS: Cutaneously VV-infected RelB(-/-), but not WT mice, exhibited weight loss, markedly impaired systemic clearance of the virus and increased contiguous propagation from the inoculation site. This was associated with a dramatically impaired generation of IFN-gamma-producing CD8(+) vaccinia-specific T cells along with decreased secretion of IFN-gamma by VV-stimulated splenocytes. The T(H)2 cytokines-IL-4, IL-5, IL-13, and IL-10-on the other hand, were overproduced. When infected intraperitoneally, RelB(-/-) mice generated robust T cell responses with good IFN-gamma production. CONCLUSION: Allergic inflammation in RelB(-/-) mice is associated with dysregulated immunity to VV encountered via the skin. We speculate that susceptibility of AD patients to overwhelming vaccinia virus infection is similarly related to ineffective T cell responses. CLINICAL IMPLICATIONS: The susceptibility of patients with AD to EV following cutaneous contact with VV is related to ineffective antiviral immune responses. PMID- 17336618 TI - TNF can contribute to multiple features of ovalbumin-induced allergic inflammation of the airways in mice. AB - BACKGROUND: TNF is thought to contribute to airway hyperreactivity (AHR) and airway inflammation in asthma. However, studies with TNF-deficient or TNF receptor-deficient mice have not produced a clear picture of the role of TNF in the AHR associated with allergic inflammation in the mouse. OBJECTIVE: We used a genetic approach to investigate the contributions of TNF to antigen-induced AHR and airway inflammation in mice on the C57BL/6 background. METHODS: We analyzed features of airway allergic inflammation, including antigen-induced AHR, in C57BL/6 wild-type and TNF(-/-) mice, using 2 different methods for sensitizing the mice to ovalbumin (OVA). RESULTS: In mice sensitized to OVA administered with the adjuvant aluminum hydroxide (alum), which develop IgE-independent and mast cell-independent allergic inflammation and AHR, we found no significant differences in OVA-induced AHR in C57BL/6-TNF(-/-) versus wild-type mice. By contrast, in mice sensitized to OVA without alum, which develop allergic inflammation that is significantly mast cell-dependent, C57BL/6-TNF(-/-) mice exhibited significant reductions versus wild-type mice in OVA-induced AHR to methacholine; numbers of lymphocytes, neutrophils, and eosinophils in bronchoalveolar lavage fluid; levels of myeloperoxidase, eosinophil peroxidase, and the cytokines IL-4, IL-5, and IL-17 in lung tissue; and histologic evidence of pulmonary inflammation. CONCLUSION: In pulmonary allergic inflammation induced in mice immunized with OVA without alum, TNF significantly contributes to several features of the response, including antigen-induced inflammation and AHR. CLINICAL IMPLICATIONS: Our findings in mice support the hypothesis that TNF can promote the allergic inflammation and AHR associated with asthma. PMID- 17336620 TI - Prevalence of asthma in children and young adults with HIV infection. PMID- 17336621 TI - Successful treatment of delayed pressure urticaria with anti-TNF-alpha. PMID- 17336619 TI - Nonlinear pharmacokinetics of high-dose recombinant fusion protein CD4-IgG2 (PRO 542) observed in HIV-1-infected children. PMID- 17336622 TI - "Black box" warnings and drug surveillance. PMID- 17336625 TI - The health of women. PMID- 17336626 TI - Targeting high-risk populations in the fight against diabetes. PMID- 17336627 TI - Revising death certification in the UK. PMID- 17336628 TI - Favourable outcomes from "mild" in-vitro fertilisation. PMID- 17336629 TI - Health statistics are no longer boring! PMID- 17336630 TI - AIDS and public security: the other side of the coin. PMID- 17336631 TI - Suckling and sugar reduce pain in babies. PMID- 17336632 TI - Robotic prostatectomy: facts or fiction? PMID- 17336636 TI - Clinical update: low back pain. PMID- 17336637 TI - Ties Boerma: improving health statistics. PMID- 17336638 TI - Mammographic screening from age 40 years. PMID- 17336639 TI - UNICEF and the UN Security Council. PMID- 17336640 TI - Mammographic screening from age 40 years. PMID- 17336641 TI - Mammographic screening from age 40 years. PMID- 17336644 TI - Estimation of death rates from pandemic influenza. PMID- 17336645 TI - Estimation of death rates from pandemic influenza. PMID- 17336646 TI - Management of severe acute malnutrition in children. PMID- 17336647 TI - Controlling multidrug-resistant tuberculosis in India. PMID- 17336650 TI - A mild treatment strategy for in-vitro fertilisation: a randomised non inferiority trial. AB - BACKGROUND: Mild in-vitro fertilisation (IVF) treatment might lessen both patients' discomfort and multiple births, with their associated risks. We aimed to test the hypothesis that mild IVF treatment can achieve the same chance of a pregnancy resulting in term livebirth within 1 year compared with standard treatment, and can also reduce patients' discomfort, multiple pregnancies, and costs. METHODS: We did a randomised, non-inferiority effectiveness trial. 404 patients were randomly assigned to undergo either mild treatment (mild ovarian stimulation with gonadotropin-releasing hormone [GnRH] antagonist co-treatment combined with single embryo transfer) or a standard treatment (stimulation with a GnRH agonist long-protocol and transfer of two embryos). Primary endpoints were proportion of cumulative pregnancies leading to term livebirth within 1 year after randomisation (with a non-inferiority threshold of -12.5%), total costs per couple up to 6 weeks after expected date of delivery, and overall discomfort for patients. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN35766970. FINDINGS: The proportions of cumulative pregnancies that resulted in term livebirth after 1 year were 43.4% with mild treatment and 44.7% with standard treatment (absolute number of patients=86 for both groups). The lower limit of the one-sided 95% CI was -9.8%. The proportion of couples with multiple pregnancy outcomes was 0.5% with mild IVF treatment versus 13.1% (p<0.0001) with standard treatment, and mean total costs were 8333 euros and 10745 euros, respectively (difference 2412 euros, 95% CI 703-4131). There were no significant differences between the groups in the anxiety, depression, physical discomfort, or sleep quality of the mother. INTERPRETATION: Over 1 year of treatment, cumulative rates of term livebirths and patients' discomfort are much the same for mild ovarian stimulation with single embryos transferred and for standard stimulation with two embryos transferred. However, a mild IVF treatment protocol can substantially reduce multiple pregnancy rates and overall costs. PMID- 17336651 TI - Trends in diabetes prevalence, incidence, and mortality in Ontario, Canada 1995 2005: a population-based study. AB - BACKGROUND: The prevalence of diabetes has been increasing greatly, but WHO's predicted 39% rise in the global rate of diabetes from 2000 to 2030 might be an underestimate. We aimed to assess diabetes trends in Ontario, Canada. METHODS: Using population-based data, including a validated diabetes database from the province of Ontario, Canada, we examined trends in diabetes prevalence and mortality from 1995 to 2005, and incidence from 1997 to 2003, in adults aged 20 years or older. FINDINGS: Age-adjusted and sex-adjusted diabetes prevalence increased by 69%, from 5.2% in a population of 7,908,562 in 1995 to 8.8% of 9,276,945 in 2005. Prevalence increased by 27% from 6.9% in a population of 8,457,720 in 2000 to 8.8% of 9,276,945 in 2005. Although prevalence rates have remained higher in people aged 50 years or older (7.1% of 3,675,554) than in those aged 20-49 years (3.5% of 5 601 391), rates increased to a greater extent in the younger population (94%vs 63%, p<0.0001). A 31% increase occurred in yearly incidence over 6 years, from 6.6 per 1000 in 1997 to 8.2 per 1000 in 2003. The adjusted mortality rate in people with diabetes fell by 25% from 1995 to 2005. INTERPRETATION: The prevalence of diabetes in Ontario, Canada increased substantially during the past 10 years, and by 2005 already exceeded the global rate that was predicted for 2030. This increase in prevalence is attributable to both rising incidence and declining mortality. Effective public-health interventions aimed at diabetes prevention are needed, as well as improved resources to manage the greater number of people living longer with the disease. PMID- 17336652 TI - Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison. AB - BACKGROUND: The burden of Plasmodium vivax infections has been underappreciated, especially in southeast Asia where chloroquine resistant strains have emerged. Our aim was to compare the safety and efficacy of dihydroartemisinin-piperaquine with that of artemether-lumefantrine in patients with uncomplicated malaria caused by multidrug-resistant P falciparum and P vivax. METHODS: 774 patients in southern Papua, Indonesia, with slide-confirmed malaria were randomly assigned to receive either artemether-lumefantrine or dihydroartemisinin-piperaquine and followed up for at least 42 days. The primary endpoint was the overall cumulative risk of parasitological failure at day 42 with a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, trial number 00157833. FINDINGS: Of the 754 evaluable patients enrolled, 466 had infections with P falciparum, 175 with P vivax, and 113 with a mixture of both species. The overall risk of failure at day 42 was 43% (95% CI 38-48) for artemether lumefantrine and 19% (14-23) for dihydroartemisinin-piperaquine (hazard ratio=3.0, 95% CI 2.2-4.1, p<0.0001). After correcting for reinfections, the risk of recrudescence of P falciparum was 4.4% (2.6-6.2) with no difference between regimens. Recurrence of vivax occurred in 38% (33-44) of patients given artemether-lumefantrine compared with 10% (6.9-14.0) given dihydroartemisinin piperaquine (p<0.0001). At the end of the study, patients receiving dihydroartemisinin-piperaquine were 2.0 times (1.2-3.6) less likely to be anaemic and 6.6 times (2.8-16) less likely to carry vivax gametocytes than were those given artemether-lumefantrine. INTERPRETATION: Both dihydroartemisinin piperaquine and artemether-lumefantrine were safe and effective for the treatment of multidrug-resistant uncomplicated malaria. However, dihydroartemisinin piperaquine provided greater post-treatment prophylaxis than did artemether lumefantrine, reducing P falciparum reinfections and P vivax recurrences, the clinical public-health importance of which should not be ignored. PMID- 17336653 TI - Pneumatosis cystoides intestinalis. PMID- 17336654 TI - Juvenile idiopathic arthritis. AB - Juvenile idiopathic arthritis is a broad term that describes a clinically heterogeneous group of arthritides of unknown cause, which begin before 16 years of age. This term encompasses several disease categories, each of which has distinct methods of presentation, clinical signs, and symptoms, and, in some cases, genetic background. The cause of disease is still poorly understood but seems to be related to both genetic and environmental factors, which result in the heterogeneity of the illness. Although none of the available drugs has a curative potential, prognosis has greatly improved as a result of substantial progresses in disease management. The most important new development has been the introduction of drugs such as anticytokine agents, which constitute a valuable treatment option for patients who are resistant to conventional antirheumatic agents. Further insights into the disease pathogenesis and treatment will be provided by the continuous advances in understanding of the mechanisms connected to the immune response and inflammatory process, and by the development of new drugs that are able to inhibit selectively single molecules or pathways. PMID- 17336655 TI - Health statistics now: are we making the right investments? AB - Increases in international funding for health have been accompanied by accelerating demand for more and better statistics, which are needed to track performance and ensure accountability. Worldwide interest in the monitoring of development, as exemplified in the Millennium Development Goals (MDGs), generates pressure for high-quality and timely data for reporting on country progress. This rapid escalation of demand has exposed major gaps in the supply of health statistics for developing countries but also provides major opportunities to increase the supply and use of sound health statistics. First, the emphasis on monitoring and evaluation is leading to proliferation of indicators and excessive reporting requirements, and needs to be refocused on systematic investments in data generation and analysis. Second, the risk of inadequate or poorly targeted investments can be kept to a minimum by understanding the causes of poor availability of health statistics, including lack of accurate measurement instruments, application of suboptimum methods of data collection, and inadequate use of methods and analyses to produce comparable estimates. Third, the preoccupation with MDGs does not take into account the rapid health transition, which implies that health statistics should systematically include a much wider array of health issues from acute infectious diseases to chronic non-communicable diseases and injuries, disaggregated by socioeconomic position. Fourth, the growing number of national household surveys, which are the main source of most population health statistics, need to be streamlined into cohesive and comprehensive country health survey programmes. Now is the time to accelerate the production and use of accurate, complete, and timely health statistics for decision-making by investing in country health information systems that should be based on an efficient and effective mix of standardised methods of data collection and analysis that meet country and international needs. PMID- 17336656 TI - Microbicide drug candidates to prevent HIV infection. AB - 25 years after the first HIV/AIDS cases emerged in 1981, the disease continues to spread worldwide, with about 15 000 new infections every day. Although highly active antiretroviral therapy (HAART) has greatly reduced the rate of HIV infection, and the spread of the epidemic, this effect has largely been seen in developed countries. More than 90% of HIV-infected people live in developing countries, most of whom do not have access to this treatment. The development of efficient, widely available, and low-cost microbicides (gels and creams can be applied topically before sex) to prevent sexually transmitted HIV infections should be given high priority. We review different categories of microbicide drugs and lead compounds, their mechanism of action, current status of development, and progress in phase III trials. PMID- 17336657 TI - Multi-organ failure after a glucagon test. PMID- 17336658 TI - Quality mental health care in medical settings: barriers and progress in maxillofacial surgery. PMID- 17336659 TI - Systematic review of multifaceted interventions to improve depression care. AB - OBJECTIVE: Depression is a prevalent high-impact illness with poor outcomes in primary care settings. We performed a systematic review to determine to what extent multifaceted interventions improve depression outcomes in primary care and to define key elements, patients who are likely to benefit and resources required for these interventions. METHOD: We searched Medline, HealthSTAR, CINAHL, PsycINFO and a specialized registry of depression trials from 1966 to February 2006; reviewed bibliographies of pertinent articles; and consulted experts. Searches were limited to the English language. We included 28 randomized controlled trials that: (a) involved primary care patients receiving acute-phase treatment; (b) tested a multicomponent intervention involving a patient-directed component; and (c) reported effects on depression severity. Pairs of investigators independently abstracted information regarding (a) setting and subjects, (b) components of the intervention and (c) outcomes. RESULTS: Twenty of 28 interventions improved depression outcomes over 3-12 months (an 18.4% median absolute increase in patients with 50% improvement in symptoms; range, 8.3-46%). Sustained improvements at 24-57 months were demonstrated in three studies addressing acute-phase and continuation-phase treatments. All interventions involved care management and required additional resources or staff reassignment to implement; interventions were delivered exclusively or predominantly by telephone in 16 studies. The most commonly used intervention features were: patient education and self-management, monitoring of depressive symptoms and treatment adherence, decision support for medication management, a patient registry and mental health supervision of care managers. Other intervention features were highly variable. CONCLUSION: There is strong evidence supporting the short-term benefits of care management for depression; critical elements for successful programs are emerging. PMID- 17336660 TI - Survivors of violence-related facial injury: psychiatric needs and barriers to mental health care. AB - OBJECTIVE: This study examined mental health needs, receptivity to psychosocial aftercare, and barriers to care among survivors of violence-related facial injuries. METHODS: Face-to-face interviews were conducted with 25 consecutively treated individuals at a hospital-based specialty outpatient clinic one month after a violence-related facial injury. To participate in the study, patients had to screen positive for an alcohol use disorder (AUD), major depression or posttraumatic stress disorder (PTSD). Participants were questioned about receptivity to an aftercare program and perceived barriers to care. RESULTS: Of those screened for study eligibility (n=62), a substantial proportion met probable criteria for AUD (31%), PTSD (34%) and major depression (35%). Among those completing the core interview (n=25), 80% met probable criteria for two or more psychiatric disorders. The majority (84%) expressed interest in psychosocial aftercare. However, barriers such as cost, insufficient information about counseling and obtaining services, transportation and preferences for self reliance were commonly endorsed. CONCLUSIONS: Survivors of violence-related facial injuries have substantial mental health needs and appear receptive to psychosocial aftercare. However, significant treatment barriers must be addressed. Findings underscore the value of a collaborative care model for treating violence-related facial trauma patients seeking care in specialty outpatient oral and maxillofacial clinics. PMID- 17336662 TI - Understanding the relationship between objective disease severity, psoriatic symptoms, illness-related stress, health-related quality of life and depressive symptoms in patients with psoriasis - a structural equations modeling approach. AB - OBJECTIVES: The aim of this study was to assess associations between objective disease severity, psoriasis symptoms, illness-related stress (IRS), health related quality of life (HRQL) and depressive symptoms in patients with psoriasis. METHOD: Cross-sectional study conducted between January and May 2005. Recruitment of 265 adult patients with psoriasis through Internet advertisements. Analysis of the validity of different measurement models and the fit of hypothesized structural models using a structural equations modeling approach. RESULTS: Thirty-two percent of the participants screened positive for depression. Because of poor discriminant validity (correlation: 0.919), IRS and HRQL were considered as one factor. The final measurement model had adequate validity and fit. A significant proportion of the variance of depressive symptoms was explained by HRQL (standardized direct effect: 0.916; P<.001). After adjustment for HRQL, objective severity of psoriasis was inversely related to depressive symptoms (standardized direct effect: -0.250; P=.094). CONCLUSION: In psoriasis - a condition without direct brain involvement - specific disease-related problems in everyday life seem to cause depression in a significant proportion of patients. It is therefore critically important to regularly assess and work to maximize HRQL in psoriasis patients. Patients with high HRQL impairment despite objectively mild psoriasis should be screened for depression. PMID- 17336661 TI - Mental disorders among adults with asthma: results from the World Mental Health Survey. AB - OBJECTIVE: Our objectives were (a) to determine which common mental disorders are associated with asthma in the general population after controlling for age and sex, and (b) to assess whether the associations of mental disorders with asthma are consistent across diverse countries. METHOD: Eighteen population surveys of household-residing adults were carried out in 17 countries (N=85,088). Mental disorders were assessed with the Composite International Diagnostic Interview 3.0, a fully structured diagnostic interview. The disorders considered here are 12-month anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, posttraumatic stress disorder and social phobia), depressive disorders (dysthymia and major depressive disorder) and alcohol use disorders (abuse and dependence). Asthma was ascertained by self-reports of lifetime diagnosis among a subsample (n=42,697). RESULTS: Pooled estimates of age adjusted and sex-adjusted odds of mental disorders among persons with asthma relative to those without asthma were 1.6 [95% confidence interval (95% CI)=1.4, 1.8] for depressive disorders, 1.5 (95% CI=1.4, 1.7) for anxiety disorders and 1.7 (95% CI=1.4, 2.1) for alcohol use disorders. CONCLUSION: This first cross national study of the relationship between asthma and mental disorders confirms that a range of common mental disorders occurs with greater frequency among persons with asthma. These results attest to the importance of clinicians in diverse settings being alert to the co-occurrence of these conditions. PMID- 17336663 TI - Does depression, apathy or cognitive impairment reduce the benefit of inpatient rehabilitation facilities for elderly hip fracture patients? AB - OBJECTIVE: Depression, apathy (amotivation) and cognitive impairment are common comorbidities in hip fracture patients, which may adversely affect functional outcome of rehabilitation. We examined whether postfracture measures of mood, motivation or cognition are associated with rehabilitation outcome (defined as functional improvement) in inpatient rehabilitation facilities (IRFs), as compared to skilled nursing facilities (SNFs). METHODS: This prospective study examined elderly patients who received surgical fixation for hip fracture and then received post-acute rehabilitation at an IRF or an SNF. Subjects were characterized at baseline for depression using the Hamilton Rating Scale for Depression, apathy/amotivation using the Apathy Evaluation Scale and mild moderate cognitive impairment using the Mini-Mental Status Examination. Functional recovery was measured over 12-week follow-up using the Functional Independence Measure. RESULTS: Fifty-eight subjects were discharged from acute care to an IRF and 39 to an SNF. Patients with depression, apathy or cognitive impairment who received rehabilitation at an IRF had significantly better functional outcomes than similarly impaired patients at SNFs, and similar outcomes such as nondepressed, motivated and cognitively intact elderly at IRFs. CONCLUSION: These findings suggest that depression, amotivation or mild-moderate cognitive impairment after hip fracture do not reduce the benefit of post-acute rehabilitation in an IRF. PMID- 17336664 TI - The association of depression and anxiety with medical symptom burden in patients with chronic medical illness. AB - BACKGROUND: Primary care patients with anxiety and depression often describe multiple physical symptoms, but no systematic review has studied the effect of anxiety and depressive comorbidity in patients with chronic medical illnesses. METHODS: MEDLINE databases were searched from 1966 through 2006 using the combined search terms diabetes, coronary artery disease (CAD), congestive heart failure (CHF), asthma, COPD, osteoarthritis (OA), rheumatoid arthritis (RA), with depression, anxiety and symptoms. Cross-sectional and longitudinal studies with >100 patients were included as were all randomized controlled trials that measure the impact of improving anxiety and depressive symptoms on medical symptom outcomes. RESULTS: Thirty-one studies involving 16,922 patients met our inclusion criteria. Patients with chronic medical illness and comorbid depression or anxiety compared to those with chronic medical illness alone reported significantly higher numbers of medical symptoms when controlling for severity of medical disorder. Across the four categories of common medical disorders examined (diabetes, pulmonary disease, heart disease, arthritis), somatic symptoms were at least as strongly associated with depression and anxiety as were objective physiologic measures. Two treatment studies also showed that improvement in depression outcome was associated with decreased somatic symptoms without improvement in physiologic measures. CONCLUSIONS: Accurate diagnosis of comorbid depressive and anxiety disorders in patients with chronic medical illness is essential in understanding the cause and in optimizing the management of somatic symptom burden. PMID- 17336665 TI - Medication safety in a psychiatric hospital. AB - OBJECTIVE: We sought to assess the epidemiology of medication errors (MEs) and adverse drug events (ADEs) in a psychiatric hospital. METHODS: We conducted a 6 month prospective observational study in a 172-bed academic psychiatric hospital. Errors and ADEs were found by way of chart review, staff reports and pharmacy intervention reports. Physicians rated incidents as to the presence of injury, preventability and severity of an injury. Serious MEs were nonintercepted MEs with potential for harm (near misses) and preventable ADEs. RESULTS: We studied 1871 admissions with 19,180 patient-days. The rate of ADEs and serious MEs were 10 and 6.3 per 1000 patient-days, respectively. Preventable ADEs accounted for 13% of all ADEs (25/191). The most common classes of drugs associated with ADEs were atypical antipsychotics (37%). Nonpsychiatric drugs accounted for only 4% of nonpreventable ADEs but were associated with nearly one third of all preventable ADEs and near misses. MEs were most frequently associated with physician orders (68%), but there was also a high rate of nursing transcription errors (20%). CONCLUSIONS: ADEs and serious MEs were common among psychiatric inpatients and similar to rates in studies of general hospital inpatients. Medication safety interventions targeting psychiatric care need further study. PMID- 17336666 TI - Mental health professionals' psychotropic pro re nata (p.r.n.) medication practices in acute inpatient mental health care: a qualitative study. AB - OBJECTIVE: This article aims to explore mental health professionals' common clinical practices associated with the prescription and administration of pro re nata (p.r.n.) psychotropic medication within acute inpatient mental health settings. METHOD: A convenience sample of 59 mental health professionals participated in face-to-face semistructured interviews that explored their p.r.n. psychotropic medication practices in acute mental health settings in a large city in the United Kingdom in 2005. Thematic content analysis was carried out. RESULTS: Mental health professionals identified a number of themes that were associated with their clinical practices. These included a balanced usefulness of p.r.n. psychotropic medications, factors that influenced their decision making and use of p.r.n. as a clinical intervention and widespread variations in clinical practices. These findings have important implications on how p.r.n. psychotropic medications use differs between individuals, professional groups and organizations within acute inpatient mental health settings. PMID- 17336667 TI - Emergence flashback in a patient with posttraumatic stress disorder. PMID- 17336669 TI - Parental mental health affects behavioral changes in children following a devastating disaster: a community survey after the 2004 Niigata-Chuetsu earthquake. PMID- 17336668 TI - Recurrent rhabdomyolysis associated with polydipsia-induced hyponatremia - a case report and review of the literature. AB - Rhabdomyolysis involves the breakdown of muscle due to an inciting insult. It has been reported to have many etiologies. Some of the more common causes are trauma and medications. Therapy involves vigorous hydration with a crystalloid or bicarbonate infusion and aims to prevent renal failure caused by the release of myoglobin. This case report describes a patient with a recurrent episode of rhabdomyolysis associated with self-induced water intoxication. He was initially treated with a 3.0% saline infusion, followed by a sodium bicarbonate infusion, with correction of his electrolytes and resolution of the rhabdomyolysis. PMID- 17336671 TI - Sample collection and handling: getting accurate results. AB - Results of many routine laboratory assays supply important diagnostic information and are an important part of patient care in many situations. Ensuring the accuracy of these results is not only important from a diagnostic standpoint but can prevent the frustration inherent when the effort of collecting and submitting samples does not yield interpretable results. This article discusses some of the routinely encountered problems (and how to avoid them) associated with performing the more commonly requested tests: complete blood cell counts, chemistry profiles, coagulation testing, and cytology specimens. The article presents a general discussion of sample collection and handling and then some specific considerations for the handling of the previously mentioned tests. PMID- 17336672 TI - Perspectives and advances in in-clinic laboratory diagnostic capabilities: hematology and clinical chemistry. AB - The typical technologies used in veterinary hematology and biochemical analyzers are reviewed, along with associated advantages and disadvantages. Guidelines for implementing a successful in-clinic laboratory are provided, including criteria for system evaluation and expectations for comparative performance evaluations. The more common problems and limitations associated with in-clinic laboratory diagnostics and how to best prevent them are also discussed. PMID- 17336673 TI - Quality control recommendations and procedures for in-clinic laboratories. AB - The design and use of quality control materials and rationale for implementation of a quality monitoring program are discussed. A simplified approach to a quality monitoring program suitable for in-clinic laboratories is presented. Use of blood films and the mean cell hemoglobin concentration value as adjuncts to quality monitoring in hematology is described. Over time, it is hoped that the profession more widely embraces, if not demands, implementation of quality monitoring for in clinic laboratory diagnostics. PMID- 17336674 TI - Hematology without the numbers: in-clinic blood film evaluation. AB - Technical advances have made it possible for many private veterinary practices to purchase reasonably priced automated hematology instruments to perform in-clinic blood analyses. Although these instruments can quickly provide "numbers" to the clinician, evaluation of a well-made blood film can often provide information critical to the interpretation of those numbers. Blood film review is essential to identify important abnormalities such as neutrophilic left shifts and toxic change, neoplastic cells, hemoparasites, and erythrocyte morphologic changes that may suggest the cause of an anemia. Additionally, the blood film provides an important quality control measure for the automated hematology results. This article outlines a simple method of blood film evaluation, highlights the most common clinically important abnormalities, and reinforces the importance of blood film evaluation as a quality control measure. PMID- 17336675 TI - Determining the significance of persistent lymphocytosis. AB - The authors provide a review of current knowledge of lymphocytosis in nonneoplastic conditions. They conclude that the list of major differentials for persistent nonneoplastic lymphocyte expansion in dogs and cats is short and that most of these conditions are relatively uncommon. Persistent lymphocytosis of small, mature, or reactive lymphocytes is most commonly the result of chronic lymphocytic leukemia or lymphoma. The first step in distinguishing nonneoplastic from neoplastic lymphocytosis is immunophenotyping by flow cytometry to determine the phenotypic diversity of the circulating cells. Clonality testing using the polymerase chain reaction for antigen receptor rearrangements assay is a useful second step in cases in which the phenotype data are equivocal. Once the diagnosis of malignancy has been established, the immunophenotype also provides prognostic information in dogs. PMID- 17336676 TI - Measurement, interpretation, and implications of proteinuria and albuminuria. AB - Proteinuria is a common disorder in dogs and cats that can indicate the presence of chronic kidney disease (CKD) before the onset of azotemia or the presence of more severe CKD after the onset of azotemia. Although a direct pathogenetic link between glomerular disease, proteinuria, and progressive renal damage has not been established, attenuation of proteinuria has been associated with decreased renal functional decline in several studies. There is a need to continue to increase our understanding of the effects of proteinuria on the glomerulus, the tubule, and the interstitium in dogs and cats. PMID- 17336677 TI - Interpretation of liver enzymes. AB - Abnormalities in liver enzymes are commonly encountered in clinical practice. Knowledgeable assessment requires a full understanding of their pathophysiology and provides an important means of detecting the earliest stage of many serious hepatobiliary disorders. The best interpretations are achieved using an integrated approach, combining historical and physical findings with routine and specialized diagnostic procedures and imaging studies. Information in this article provides the foundation, by example, for understanding the reliability of single time point enzyme measurements, the value of sequential measurements, the importance of interpreting the activity of enzymes in light of their half life and tissue of origin, and the influence of the induction phenomenon. PMID- 17336678 TI - New challenges for the diagnosis of feline immunodeficiency virus infection. AB - Vaccination of cats against feline immunodeficiency virus (FIV) with a whole virus vaccine results in rapid and persistent production of antibodies that are indistinguishable from those used for diagnosis of FIV infection. There are no diagnostic tests available for veterinary practitioners at the present time to resolve the diagnostic dilemma posed by use of whole-virus vaccines for protection of cats against FIV. There is a great need for development of commercially available rapid diagnostic tests that conform to differentiation of infected from vaccinated animals standards. PMID- 17336679 TI - Maximizing the diagnostic value of cytology in small animal practice. AB - Cytology is a valuable diagnostic tool in veterinary medicine. A review of the literature indicates its utility in evaluation of specific lesions. The information obtained from cytology is greatly enhanced by a good understanding of its advantages and disadvantages and an open and interactive relationship between clinicians and pathologists. Critical selection of appropriate lesions, good sampling technique, quality sample handling, and provision of a complete clinical history and lesion description enhance the utility of the information returned to the clinician by the pathologist. A good cytologic diagnosis is a team effort. PMID- 17336680 TI - Fungal diagnostics: current techniques and future trends. AB - The diagnosis of fungal disease is a challenge that requires diligent attention to history and clinical signs as well as an astute ability to interpret laboratory data. Because fungal disease can mimic other infectious and neoplastic diseases in clinical presentation, the clinician has to be aware of fungal diseases common locally as well as in other regions of the country. A global approach to the diagnosis of fungal disease that correlates clinical signs as well as physical examination, clinical pathology, and histopathology findings with serology, culture, and the newer immunohistochemical and molecular techniques, where available, is the best approach to optimize the identification of the underlying agent. PMID- 17336681 TI - Getting the most from dermatopathology. AB - Dermatohistopathology is one of the most powerful diagnostic tools in clinical dermatology. It is a process in which the veterinary clinician and the veterinary pathologist must consider themselves a team in patient care. The veterinary clinician must know when biopsies are indicated; be able to select lesions to biopsy that are likely to yield diagnostic results; skillfully procure the biopsy samples; and provide the pathologist with an accurate history, clinical description, and clinical differential diagnosis. The pathologist should have particular interest and expertise in dermatohistopathology, be readily accessible to the clinician, and be vigilant in the pursuit of an accurate histologic description and diagnosis. PMID- 17336684 TI - Genetics of human lupus nephritis. AB - Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease in which glomerulonephritis represents one of the most severe clinical presentations. Numerous linkage and association studies, as well as the analysis of murine models, have provided ample evidence for a genetic basis for SLE. Genetic susceptibility to SLE results from the combined actions of multiple alleles, each of them conferring a modest incremental risk. SLE susceptibility genes have been identified in 3 major pathways: apoptosis, lymphocyte activation, and clearance of immune complexes and/or apoptotic debris. There also now is evidence that, within SLE patients, renal end-organ targeting also has a genetic basis, which can be divided into 2 branches. There is evidence that susceptibility alleles that are associated with a greater disease severity also are associated with lupus nephritis. There also is evidence for a set of kidney specific genes that are likely to amplify or to sensitize to the autoimmune pathology. PMID- 17336685 TI - Genetic basis of murine lupus nephritis. AB - Systemic lupus erythematosus is a generalized autoimmune disease affecting multiple end-organs including the kidneys. Glomerulonephritis is a leading cause of death in lupus, both in patients and murine models that develop disease spontaneously. Genetic mapping studies have uncovered several genetic intervals that confer susceptibility to nephritis both in human beings and in mice. This review surveys the genomic positions of these nephritis susceptibility loci in murine lupus. Currently we know very little about the molecular identities of the culprit genes within these mapped loci and whether these genetic elements contribute to nephritis directly in a renal-intrinsic fashion or indirectly by augmenting the formation of pathogenic autoantibodies. The next decade is likely to witness a significant broadening of our understanding of how different genes and molecules might facilitate end-organ damage in lupus. PMID- 17336686 TI - The pathology of lupus nephritis. AB - An international working group of clinicians and pathologists met in 2003 under the auspices of the International Society of Nephrology (ISN) and the Renal Pathology Society (RPS) to revise and update the 1982 and 1995 World Health Organization classification of lupus glomerulonephritis. This article compares and contrasts the ISN/RPS classification and the antecedent World Health Organization classifications. Although systemic lupus erythematosus is the prototypical systemic immune-complex disease, several non-immune-complex mechanisms of glomerular injury and dysfunction have been proposed, and this article summarizes the evidence supporting the pathogenic mechanisms of lupus vasculitis, glomerular capillary thrombosis, and lupus podocytopathy. The most significant and controversial feature of the ISN/RPS classification is the separation of diffuse glomerulonephritis into separate classes with either segmental (class IV-S) or global (class IV-G) lesions. Several groups have tested the prognostic significance of this separation, and this article discusses the implications of these studies for the ISN/RPS classification. PMID- 17336687 TI - The antiphospholipid syndrome. AB - The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the clinical association of antiphospholipid autoantibodies (aPL) with a syndrome of hypercoagulability that can affect any blood vessel, irrespective of type or size. Involvement of larger vessels, such as arteries or veins, manifests in the form of thrombosis or embolism, whereas involvement of smaller vessels, including capillaries, arterioles, and venules, manifests as thrombotic microangiopathy. Virtually any organ in the body, including the kidney, can be affected. Here, we review the basic principles and recent advances in our understanding of APS, and discuss the broad spectrum of renal diseases that have been observed in association with this syndrome. We also discuss the impact that APS may have on pre-existing renal disease as well as current recommendations for treatment of APS. PMID- 17336689 TI - Leukocyte-renal epithelial cell interactions regulate lupus nephritis. AB - Renal disease is the major cause of morbidity in patients with lupus. MRL Fas(lpr) mice share features with human lupus. The tempo, predictability, and homogeneous expression of disease in MRL-Fas(lpr) mice make them an excellent tool to probe the pathogenesis of lupus nephritis and to identify therapeutic targets. This article focuses on the concepts that renal parenchymal cells are active participants that regulate immune responses in the kidney, and that the interaction between parenchymal cells and leukocytes (macrophages, T cells) determine whether the kidney is protected or destroyed during lupus nephritis. In particular we review the role of macrophages, fueled by the principal macrophage developmental molecule, colony stimulating factor-1, in lupus nephritis, and we review T cells and costimulatory pathways and the interaction of these leukocytes with renal parenchymal cells that regulate lupus nephritis. PMID- 17336688 TI - T cells and B cells in lupus nephritis. AB - T and B lymphocytes play diverse roles at multiple stages in the development and progression of lupus nephritis. Disruption of T- and B-cell regulatory functions by environmental and genetic influences permits pathogenic effectors to emerge in disease. New insights into the biology of these multifunctional cells offer novel targets for intervention in lupus nephritis and systemic autoimmunity. PMID- 17336690 TI - Complement in lupus nephritis: the good, the bad, and the unknown. AB - The complement system consists of 3 pathways and more than 30 proteins, including those with biological activity that directly or indirectly mediate the effects of this system, plus a set of regulatory proteins necessary to prevent injudicious complement activation on host tissue. The role for complement in the pathogenesis of systemic lupus erythematosus (SLE) is paradoxic. On one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classic pathway components are associated with an increased risk for SLE. On the other hand, immune complex-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathologic features that are logical consequences of complement activation. By using accurate mouse models of SLE, we have gained remarkable insights into pathogenic features likely relevant to the human disease, and the ability to test potential therapies, some of which have made it to standard clinical use. Studies in genetically altered mice and using recombinant protein inhibitors of complement have confirmed what was believed but unproven-early complement proteins C1q and C4 are protective whereas complement activation later in the pathways is proinflammatory and deleterious. Two complement inhibitors, soluble complement receptor 1 (TP10, Avant Immunotherapeutics, Needham, MA) and a monoclonal anti-C5 antibody (Eculizumab, Alexion Pharmaceuticals, Inc., Cheshire, CT) have been shown to inhibit complement safely and now are being investigated in a variety of clinical conditions. Although these and others earlier in their clinical development hold promise to be used therapeutically in lupus nephritis, this optimism must be tempered by the fact that the clinical trials to prove this remain fraught with obstacles. PMID- 17336691 TI - Chemokines and chemokine receptors as therapeutic targets in lupus nephritis. AB - Recruitment of leukocytes is a characteristic feature of tissue injury in systemic lupus erythematosus, including lupus nephritis. Locally secreted chemokines and their receptors are important mediators of leukocyte recruitment to the specific sites of immune complex injury, and contribute to renal inflammatory disease in the initiation and progression phase. Therefore, chemokines and chemokine receptors represent potential therapeutic targets in lupus nephritis. In this review we summarize available experimental and human data supporting their functional role in lupus nephritis. Moreover, interventional studies with chemokine and chemokine receptor antagonists that show the therapeutic potential of chemokine antagonists in experimental models of lupus nephritis and potentially in human renal disease are discussed. PMID- 17336692 TI - Interleukin-18 and the pathogenesis of inflammatory diseases. AB - Several autoimmune diseases are thought to be mediated in part by interleukin (IL)-18. Many are those with associated increased interferon-gamma (IFNgamma) levels such as systemic lupus erythematosus, macrophage activation syndrome, rheumatoid arthritis, Crohn's disease, psoriasis, and graft-versus-host disease. In addition, ischemia, including acute renal failure in human beings, appears to involve IL-18. Animal studies also support the concept that IL-18 is a key player in models of lupus erythematosus, atherosclerosis, graft-versus-host disease, and hepatitis. Unexpectedly, IL-18 plays a role in appetite control and the development of obesity. IL-18 is a member of the IL-1 family; IL-1beta and IL-18 are related closely, and both require the intracellular cysteine protease caspase 1 for biological activity. The IL-18 binding protein, a naturally occurring and specific inhibitor of IL-18, neutralizes IL-18 activities and has been shown to be safe in patients. Other options for reducing IL-18 activities are inhibitors of caspase-1, human monoclonal antibodies to IL-18, soluble IL-18 receptors, and anti-IL-18 receptor monoclonal antibodies. PMID- 17336693 TI - Human clinical trials in lupus nephritis. AB - Improved patient survival after treatment of lupus nephritis with corticosteroids, immunosuppressants, and renal replacement therapy allows greater emphasis on long-term management issues. In particular, the recent focus has been on therapies to treat nephritis with fewer adverse effects compared with cyclophosphamide and immunosuppressive regimens. Issues complicating clinical trial design in lupus nephritis have severely limited comparisons across trials. These issues, including recognition and stratification of high-risk populations, comparable remission and response criteria, and appropriate use and interpretation of activity and damage indices have been the subject of much discussion and emerging consensus. Mycophenolate mofetil (MMF) has been used in the field of transplantation for more than 10 years. After initial anecdotal reports describing the benefits of MMF in the treatment of lupus nephritis, randomized controlled trials have established a role for MMF in the treatment of lupus nephritis. A host of newer agents including rituximab, abatacept, and monoclonal antibodies blocking costimulatory targets are in current clinical trials for lupus nephritis. As long-term outcomes in lupus nephritis improve, the toxicity of therapy and risk of relapse become increasingly important determinants of the choice of therapeutic agents. PMID- 17336695 TI - In the literature: on clinical performance measures and outcomes among hemodialysis patients. PMID- 17336696 TI - Lack of synergistic effects of metabolic syndrome and plasma fibrinogen on coronary events and mortality in moderate CKD. AB - BACKGROUND: Metabolic syndrome and inflammation are interlinked in patients with moderate chronic kidney disease (CKD). METHODS: We examined whether these 2 conditions exert additive or multiplicative joint effects on subsequent coronary events and death in 710 Atherosclerosis Risk in Communities Study participants with a glomerular filtration rate less than 60 mL/min/1.73 m(2) (<1.0 mL/s). RESULTS: From the lowest to the highest quartile of level of plasma fibrinogen (an inflammation marker), the prevalence of metabolic syndrome (39%, 46%, 47%, and 64%; P < 0.001) increased. In multivariate Cox regression models, each 100 mg/dL increase in plasma fibrinogen level was associated with a significantly increased hazard of fatal/nonfatal coronary events (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.33 to 1.98) and death (HR, 1.49; 95% CI, 1.28 to 1.74). In the same models, metabolic syndrome also was associated with coronary events (HR, 1.49; 95% CI, 1.01 to 2.20) and death (HR, 1.40; 95% CI, 1.01 to 1.94). There was no significant interaction of plasma fibrinogen and metabolic syndrome with respect to risk of both fatal/nonfatal coronary events (P = 0.79) and death (P = 0.29). However, patients without metabolic syndrome and in the lowest quartile of plasma fibrinogen levels had the lowest incidence of fatal/nonfatal coronary events or death, whereas those with metabolic syndrome and in the highest quartile of plasma fibrinogen levels had the highest incidence of these events. CONCLUSION: Inflammation is associated strongly with metabolic syndrome in patients with moderate CKD. Inflammation and metabolic syndrome have additive and not multiplicative joint effects on coronary events and death. PMID- 17336698 TI - Simvastatin for secondary prevention of all-cause mortality and major coronary events in patients with mild chronic renal insufficiency. AB - BACKGROUND: A potentially modifiable risk factor for cardiovascular disease in patients with mild chronic renal insufficiency is dyslipidemia. Few studies examined the effects of statins on all-cause mortality and major coronary events in patients with renal dysfunction. METHODS: We performed a post hoc analysis from the Randomized Trial of Cholesterol Lowering in 4,444 Patients with Coronary Heart Disease: The Scandinavian Simvastatin Survival Study. Of 4,444 participants, 2,314 (52.1%) had mild chronic renal insufficiency defined as an estimated glomerular filtration rate less than 75 mL/min/1.73 m(2) (<1.25 mL/s), measured using the Modification of Diet in Renal Disease equation. The primary end point was all-cause mortality. RESULTS: During the follow-up period, simvastatin use was associated with decreased all-cause mortality (adjusted hazard ratio [HR], 0.69; confidence interval [CI], 0.54 to 0.89) in the 2,314 participants with mild chronic renal insufficiency. Rates of major coronary events (adjusted HR, 0.67; CI, 0.56 to 0.79) and coronary revascularization (adjusted HR, 0.62; CI, 0.49 to 0.77) also were significantly lower in the simvastatin group. No significant decreases in stroke incidence were observed in the simvastatin group (adjusted HR, 0.88; CI, 0.55 to 1.39). The side-effect profile was similar between the 2 treatment groups. CONCLUSION: Simvastatin therapy appears to be effective and safe for the secondary prevention of all cause mortality and major coronary events in patients with mild chronic renal dysfunction. PMID- 17336697 TI - Association of cystatin C with poor exercise capacity and heart rate recovery: data from the heart and soul study. AB - BACKGROUND: Cystatin C, an alternative serum measure of kidney function, is a stronger predictor of cardiovascular events than creatinine or estimated glomerular filtration rate (eGFR). We hypothesized that serum cystatin C concentration would have a stronger more linear association with cardiovascular functional status than creatinine-based measures in outpatients with established coronary heart disease (CHD). METHODS: We measured serum cystatin C, serum creatinine, and eGFR in 906 outpatients with established CHD. We examined the association of these 3 measures of kidney function with treadmill exercise capacity (metabolic equivalent tasks achieved) and heart rate recovery (HRR) between peak and 1 minute after exercise by using linear and logistic regression. RESULTS: Higher cystatin C concentrations were associated linearly with worse treadmill exercise capacity and HRR. The proportion of participants with poor exercise capacity (metabolic equivalent tasks achieved < 5) was 45% (99 of 222 participants) among those with cystatin C levels in the highest quartile (>1.30 mg/L) compared with 12% (29 of 241 participants) among those with cystatin C levels in the lowest quartile (<0.92 mg/L; adjusted odds ratio, 3.2; 95% confidence interval, 1.6 to 6.5; P = 0.001). The proportion of participants with poor HRR (<16 beats/min) was 42% (92 of 214 participants) among those with cystatin C levels in the highest quartile compared with 16% (37 of 238 participants) among those with cystatin C levels in the lowest quartile (adjusted odds ratio, 2.2; 95% confidence interval, 1.2 to 4.0; P = 0.01). The lowest quartile of eGFR (<61.8 mL/min [<1.03 mL/s]) was associated with decreased exercise capacity and prolonged HRR, but no difference was observed across the upper 3 quartiles of eGFR. CONCLUSION: In patients with established CHD, cystatin C concentrations are associated linearly with worse exercise capacity and HRR. Cystatin C detects an association of impaired kidney function with decreased HRR and exercise capacity that is not fully captured using creatinine-based measurements. PMID- 17336699 TI - Kidney disease as a predictor of mortality in chronic spinal cord injury. AB - BACKGROUND: The purpose of this study is to assess the predictive value of proteinuria and creatinine clearance (CrCl) in relation to mortality in patients with spinal cord injury. METHODS: Computerized medical records covering 6 to 11 years were reviewed in 2004 to determine all-cause mortality. Long-term survival was assessed by means of Kaplan-Meier analysis. Multiple and stepwise Cox proportional hazards models were used to identify risk factors for mortality. The dependent variable was duration of survival in months. Potential predictors included proteinuria, CrCl, age, duration and type of injury, type of bladder management, ethnicity, diabetes mellitus, hypertension, coronary artery disease, hematocrit, serum albumin level, and serum cholesterol level. RESULTS: With the Cox model, proteinuria with protein of 500 mg/d or greater (hazard ratio [HR], 2.98), CrCl less than 60 mL/min (<1.00 mL/s; HR, 3.89), or both (HR, 7.86) were associated independently with increased mortality. When added individually to the base Cox model, bladder catheter use (HR, 1.70) and age (HR, 1.05) also were independently predictive of time to death. Patients with preserved CrCl (>or=60 mL/min) and no proteinuria (protein < 500 mg/d) had a significantly greater duration of survival compared with patients with proteinuria (protein >or= 500 mg/d), decreased CrCl (<60 mL/min), or both (median survival, 120, 86, 87, and 47 months, respectively; P < 0.0001). There was no significant difference in survival in patients with proteinuria (protein >or= 500 mg/d) and preserved CrCl (>or=60 mL/min) compared with those with no proteinuria (protein < 500 mg/d) and decreased CrCl (<60 mL/min; P = 0.90). However, those with both proteinuria and decreased CrCl had significantly worse survival compared with those with only 1 condition (P < 0.01). Kidney disease was associated with an increase in both cardiovascular and noncardiovascular mortality. CONCLUSION: The presence of either proteinuria with protein of 500 mg/d or greater or CrCl less than 60 mL/min is associated independently with increased mortality in the chronic spinal cord injury population. The presence of both conditions further increases this risk. PMID- 17336700 TI - A genome-wide search for linkage to renal function phenotypes in West Africans with type 2 diabetes. AB - BACKGROUND: Reduced renal function often is a major consequence of diabetes and hypertension. Although several indices of renal function (eg, creatinine clearance) are clearly heritable and show linkage to several genomic regions, the specific underlying genetic determinants are still being sought. The purpose of this study is to conduct a genome-wide search for regions linked to 3 renal function phenotypes, serum creatinine, creatinine clearance, and glomerular filtration rate (GFR), in persons with type 2 diabetes. METHODS: A genome-wide panel of 372 autosomal short tandem repeat markers at an average spacing of 9 centimorgan were typed in 691 patients with type 2 diabetes (321 sib pairs and 36 half-sib pairs) in an affected sib pair study in West Africa. Linkage analysis was conducted with the 3 phenotypes by using a multipoint variance components linkage method. RESULTS: Creatinine clearance showed higher logarithm of odds (LOD) score than the other 2 phenotypes. Linkage to creatinine clearance was observed on chromosomes 16 (marker D16S539, LOD score of 3.56, empirical P = 0.0001), 17 (D17S1298, LOD score of 2.08, empirical P = 0.0018), and 7 (D7S1818, LOD score of 1.84, nominal P = 0.00181, empirical P = 0.0022). Maximum LOD scores for serum creatinine were observed on chromosomes 10 (D10S1432, LOD score of 2.53, empirical P = 0.0001) and 3 (D3S2418, LOD score of 2.21, empirical P = 0.0003) and for GFR on chromosomes 6 (D6S1040, LOD score of 2.08, empirical P = 0.0001) and 8 (D8S256, LOD score of 1.80, empirical P = 0.0001). Several of these results are replications of significant findings from other genome scans. CONCLUSION: A genome-wide scan for serum creatinine, creatinine clearance, and GFR in a West African sample showed linkage regions that may harbor genes influencing variation in these phenotypes. Potential candidate genes in these regions that have been implicated in diabetic nephropathy and/or renal damage in models of hypertension include CYBA (or P22PHOX) (16q24), NOX1 (10q22), and NOX3 (6q25.1-q26). PMID- 17336701 TI - Aspirin treatment is associated with a significantly decreased risk of Staphylococcus aureus bacteremia in hemodialysis patients with tunneled catheters. AB - BACKGROUND: Hemodialysis patients with tunneled catheters are at increased risk of bacteremic Staphylococcus aureus infections. In vitro and in vivo studies showed that aspirin has direct antistaphylococcal effects by inhibiting expression of alpha-toxin and matrix adhesion genes through activation of sigma factor B stress-induced operon. We hypothesized that long-term treatment with aspirin may decrease the frequency of S aureus bacteremia in such patients. METHODS: We retrospectively analyzed electronic medical records for a variety of clinical parameters, including catheter dwell times, blood culture results, and aspirin use in our dialysis population. RESULTS: A total of 4,722 blood cultures were performed in 872 patients during more than 476 patient-catheter-years. There was a lower rate of catheter-associated S aureus bacteremia in patients treated with aspirin versus those not treated with aspirin (0.17 versus 0.34 events/patient-catheter-year, P = 0.003), whereas no such difference was observed for other bacteria. This association was dose dependent, seen mostly with the 325 mg aspirin dose. Using the Cox proportional hazard method, risk to develop a first episode of S aureus bacteremia decreased by 54% in patients using aspirin (confidence interval, 24 to 72; P = 0.002). Aspirin was associated with decreased risk of: (1) a first episode of methicillin-resistant S aureus bacteremia and (2) metastatic complications during the first episode of catheter-related S aureus bacteremia. CONCLUSION: These data are consistent with our clinical hypothesis that aspirin has a clinically useful antistaphylococcal effect in the dialysis population. PMID- 17336702 TI - Distribution of coronary artery disease and relation to mortality in asymptomatic hemodialysis patients. AB - BACKGROUND: Long-term dialysis patients have a high incidence of myocardial infarction and cardiovascular death, but the incidence of coronary artery disease (CAD) in asymptomatic patients, distribution of coronary obstruction, and relationship between lesion location and mortality are unknown. METHODS: We studied 67 asymptomatic hemodialysis patients who volunteered for coronary angiography. Coronary stenoses of 50% or greater were documented, and the location of each within the proximal, midportion, or distal segment of the coronary vessel was recorded. Patients were followed up until death or renal transplantation. Cox proportional hazards regression was performed to analyze the relationship of lesion location with mortality. RESULTS: Obstructive CAD was common. Twenty-eight subjects (41.7%) had 50% or greater stenosis in at least 1 epicardial vessel, and 19 subjects (28.5%) had evidence of CAD within the proximal third of an epicardial vessel. After a median follow-up of 2.7 years, the presence of proximal CAD was associated with a marked increase in risk of death (adjusted hazard ratio, 3.14; 95% confidence interval, 1.34 to 7.33; P = 0.008) and was associated more strongly with mortality than multivessel disease or left anterior descending disease. CONCLUSION: CAD is common in asymptomatic dialysis patients, and stenoses frequently are located within the proximal coronary arteries, where they are associated with markedly increased risks of death. Additional studies are needed to determine whether proximal disease is a modifiable risk factor for cardiovascular mortality in dialysis patients. PMID- 17336703 TI - Presence of abdominal aortic calcification is significantly associated with all cause and cardiovascular mortality in maintenance hemodialysis patients. AB - BACKGROUND: Although abdominal aortic calcification (AAC) is reported as a predictor for cardiovascular mortality in the general population, it is unknown whether this is also true in hemodialysis patients in whom vascular calcification and cardiovascular diseases are highly prevalent. STUDY DESIGN: Cohort study. SETTINGS & PARTICIPANTS: 515 patients on maintenance hemodialysis therapy at a single center. PREDICTOR: AAC evaluated in a plain roentgenograph of the lateral abdomen at baseline. OUTCOMES & MEASUREMENTS: All-cause and cardiovascular death. RESULTS: Mean age was 60 +/- 12 (SD) years. AAC was present in 291 patients (56.5%). During a mean follow-up period of 51 +/- 17 months, there were 103 all cause deaths, of which 41 were from cardiovascular diseases. Of patients with and without AAC, 27.8% and 9.8% died, respectively (11.6% and 3.1% of cardiovascular diseases, respectively). Kaplan-Meier analysis showed that all-cause mortality was significantly greater in patients with AAC compared to those without (P < 0.0001, log-rank test). Similarly, cardiovascular mortality was significantly greater in the former than in the latter group (P = 0.0001, log-rank test). Multivariate Cox proportional hazards analysis found that the presence of AAC was significantly associated with increased all-cause mortality (hazard ratio, 2.07; 95% confidence interval, 1.21 to 3.56; P < 0.01) and increased cardiovascular mortality (hazard ratio, 2.39; 95% confidence interval, 1.01 to 5.66; P < 0.05) after adjustment for age, hemodialysis duration, presence of diabetes, serum albumin level, and C-reactive protein level. LIMITATIONS: Nonquantitative assessment of AAC and the lack of information for medication and history of cardiovascular diseases. CONCLUSION: The presence of AAC is significantly associated with both all-cause and cardiovascular mortality in hemodialysis patients, suggesting that careful attention should be given to the presence of AAC in a simple radiograph of the lateral abdomen as a prognostic indicator. PMID- 17336704 TI - Diuretic use, residual renal function, and mortality among hemodialysis patients in the Dialysis Outcomes and Practice Pattern Study (DOPPS). AB - BACKGROUND: Information about residual renal function (RRF) and outcomes associated with practices of diuretic use in patients with end-stage renal disease is not available worldwide. METHODS: Diuretic use was investigated in 16,420 hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study, a prospective observational study of hemodialysis patients selected from nationally representative facilities on 3 continents. Logistic regressions were used to investigate associations between diuretic use and patient characteristics. Outcomes of interdialytic weight gain, increased serum potassium and phosphorus levels, and odds of retaining RRF after 1 year were investigated. Cox regression was used to analyze the association between mortality and diuretic use. RESULTS: Facility diuretic use varied substantially from 0% to 83.9% of patients. Diuretic use decreased sharply after the start of dialysis therapy. Loop diuretic use ranged from 9.2% in the United States to 21.3% in Europe, whereas use within 90 days of starting dialysis therapy ranged from 25.0% in the United States to 47.6% in Japan. Diuretic use was associated with lower interdialytic weight gain and lower odds of hyperkalemia (potassium > 6.0 mmol/L). Patients with RRF on diuretic therapy had almost twice the odds of retaining RRF after 1 year in the study versus patients not on diuretic therapy. Patients administered diuretics had a 7% lower all-cause mortality risk (P = 0.12) and 14% lower cardiac-specific mortality risk (P = 0.03) versus patients not administered diuretics. CONCLUSION: Variation exists in facility practices of diuretic use. In patients with RRF, there may be benefit associated with continuing diuretic use rather than automatically discontinuing diuretic therapy at dialysis initiation. PMID- 17336705 TI - Subclinical vitamin K deficiency in hemodialysis patients. AB - BACKGROUND: Subclinical vitamin K deficiency increasingly is associated with extraosseous calcification in healthy adults. Nondietary determinants of vitamin K status include apolipoprotein E (apoE) genotype, which may influence vitamin K transport to peripheral tissues. METHODS: Serum phylloquinone concentrations and percentage of uncarboxyated osteocalcin (%ucOC) were measured by means of high performance liquid chromatography and radioimmunoassay in 142 hemodialysis patients, respectively. ApoE phenotype was determined by means of isoelectric focusing of delipidated serum samples and Western blot analysis. Clinical and laboratory data were obtained by using chart review. RESULTS: Mean age was 62.6 +/- 14.8 (SD) years. Mean phylloquinone level was 0.99 +/- 1.12 nmol/L; 29% of patients had levels less than 0.4 nmol/L. There was no association between phylloquinone level and %ucOC. There were positive correlations between phylloquinone and total cholesterol (P = 0.017), triglyceride (P = 0.022), and ionized calcium levels (P = 0.019). There was a negative correlation between phylloquinone level and dialysis adequacy (P = 0.002). Mean %ucOC was 51.1% +/- 25.8%, and 93% of subjects had values greater than 20%. There were positive correlations between %ucOC and dialysis vintage (P < 0.001), phosphate level (P < 0.001), parathyroid hormone level (P < 0.001), albumin level (P = 0.035), and ionized calcium level (P = 0.046). Seventeen percent of patients were apoE4. Mean %ucOC was significantly greater in apoE4 carriers compared with all other apoE phenotypes (60.1% +/- 28.4% versus 47.8% +/- 24.4%; P = 0.035). In multiple regression analysis with phylloquinone level forced in, independent predictors of %ucOC were phosphate level, dialysis vintage, parathyroid hormone level, and apoE4. CONCLUSION: These data indicate suboptimal vitamin K status in hemodialysis patients, shown by low phylloquinone concentrations and high %ucOC in 29% and 93% of subjects, respectively. The apoE4 allele influences osteocalcin gamma-carboxylation in hemodialysis patients. PMID- 17336706 TI - Minimodeling reduces the rate of cortical bone loss in patients with secondary hyperparathyroidism. AB - BACKGROUND: Secondary hyperparathyroidism often causes progressive cortical thinning because of increased bone resorption at the endocortical surface and increases cortical porosity because of increased resorption at the intracortical surface. Because bone formation by minimodeling has not yet been reported in cortical bone, we investigated the effects of cortical minimodeling on the decrease in rate of bone loss. METHODS: Thirty-five patients with secondary hyperparathyroidism were enrolled. Remodeling and minimodeling parameters at the endocortical and periosteal surfaces, as well as at the intracortical surface, were measured. Relationships between remodeling parameters and minimodeling parameters at each surface were investigated by using linear regression analysis. Cortical bone specimens were classified into 3 groups according to cortical width and cortical porosity values. Relationships of minimodeling parameters at the endocortical surface with cortical width and at the intracortical surface with cortical porosity were investigated. RESULTS: Some minimodeling parameters showed positive correlations with serum parathyroid hormone levels and remodeling parameters. Minimodeling bone volume at the endocortical surface was greater in the narrow-cortical-width group than wide-cortical-width group, possibly slowing the progression of cortical thinning. Minimodeling volume at the intracortical surface was greater in the high-porosity than low-porosity group, possibly slowing the progression of intracortical resorption space enlargement. Minimodeling of the periosteal surface was found in 1 specimen. CONCLUSION: Results show enhanced cortical minimodeling in patients with secondary hyperparathyroidism, possibly representing the decrease in rate of cortical bone loss. PMID- 17336707 TI - Peritoneal mast cells in peritoneal dialysis patients, particularly in encapsulating peritoneal sclerosis patients. AB - BACKGROUND: We assumed that increased mast cell numbers contribute substantially to the fibrosis often seen in the peritoneum of peritoneal dialysis (PD) patients, particularly those with encapsulating peritoneal fibrosis (EPS). Therefore, we investigated mast cells in different pathological conditions of the peritoneum. METHODS: One hundred fifteen tissue probes with different peritoneal pathological states were selected (normal, n = 20; chronic appendicitis, n = 25; herniotomy, n = 24; fibrosis, n = 11; PD, n = 26; and EPS, n = 9). For staining of mast cells, we used alpha-naphtol-AS-d-chloracetate-esterase and mast cell tryptase. Next, we counted numbers of mast cells per square millimeter. Tryptase was measured by using image analysis. RESULTS: Measurements by means of both methods correlated well (r = 0.812). Numbers of mast cells per square millimeter were as follows: normal, 26 +/- 16; chronic appendicitis, 241 +/- 217; herniotomy, 115 +/- 88; fibrosis, 99 +/- 66; PD, 81 +/- 64, and EPS, 24 +/- 23 (P = 0.00006). Amounts of tryptase present were 2.900 +/- 0.118, 2.871 +/- 0.150, 2.733 +/- 0.183, 3.041 +/- 0.176, 2.780 +/- 0.184, and 2.609 +/- 0.234, respectively (P = 0.00002). CONCLUSION: We found upregulation of mast cells in specimens of chronic inflammatory diseases of the peritoneum. This also was true for PD patients, with the exclusion of patients with EPS. Therefore, loss-of control functions of mast cells may contribute to the ill-understood disease entity of EPS. PMID- 17336708 TI - Monitoring antitumor efficacy of rapamycin in Kaposi sarcoma. AB - BACKGROUND: The clinical challenge for the application of rapamycin and its derivatives as anticancer drugs is the ability to prospectively identify which tumors will be sensitive to mammalian target of rapamycin (mTOR) inhibition. The present study is designed to explore mTOR signaling in peripheral-blood mononuclear cells (PBMCs) from renal transplant recipients with Kaposi sarcoma and ascertain whether it would reflect deregulation of the AKT-mTOR pathway in skin cancer tissue and might help identify which patients would benefit from rapamycin treatment, as well as to monitor their clinical response. METHODS: We measured basal and in vivo stimulated AKT and P70 S6 kinase (P70(S6K)) phosphorylation in PBMCs from 37 cyclosporine A-treated patients, 10 of whom had Kaposi sarcoma, before and 6 months after conversion to rapamycin therapy. RESULTS: Patients with Kaposi sarcoma showed markedly increased basal P70(S6K) activation and depressed phosphorylation of AKT. Long-term treatment with rapamycin was associated with marked inhibition of basal and stimulated phosphorylation of both AKT and P70(S6K), in parallel with regression of the dermal neoplasm. CONCLUSION: Overactivation of basal P70(S6K) in PBMCs from renal transplant recipients appears to be associated with the presence of Kaposi sarcoma dermal lesions; conversely, kinase inhibition is linked to regression of skin cancer lesions. Thus, monitoring P70(S6K) phosphorylation can help predict and monitor the biological effectiveness of rapamycin in renal transplant recipients with Kaposi sarcoma and possibly adjust the biologically active doses of the mTOR inhibitor. PMID- 17336709 TI - Thirty-five years of hemodialysis: two case reports as a tribute to Nils Alwall. AB - Two patients with long-term (35 years) survival on hemodialysis are described. Kidney replacement therapy for these patients was initiated by a pioneer in hemodialysis, Nils Alwall, in 1968 and 1971, respectively. Kidney transplantation was attempted twice in both patients; however, the dialysis-free interval was less than 18 months in both patients. These patients represent two of the longest known survivors on hemodialysis worldwide. Factors that may have influenced their survival are discussed, and the complications that have occurred over the years are presented. PMID- 17336710 TI - Successful treatment of renal amyloidosis due to familial cold autoinflammatory syndrome using an interleukin 1 receptor antagonist. AB - Familial cold autoinflammatory syndrome (FCAS) is an autosomal dominant disorder characterized by episodic fever, arthralgias, conjunctivitis, and rash triggered by cold exposure. FCAS is rarely associated with progressive renal insufficiency caused by renal amyloidosis. The genetic defect in patients with this disorder is caused by a mutation in the gene encoding the protein cryopyrin, leading to uninhibited activation of systemic inflammation through specific cellular signaling with increased production of a number of key cytokines, including interleukin 1. We describe the successful treatment of a patient with renal amyloidosis caused by FCAS by using a novel interleukin 1-receptor antagonist. Use of specific anticytokine therapy may be a new paradigm in the treatment of patients with renal amyloidosis caused by systemic inflammatory diseases. PMID- 17336711 TI - The early history of dialysis for chronic renal failure in the United States: a view from Seattle. AB - Forty-seven years have passed since the first patient started treatment for chronic renal failure by repeated hemodialysis (HD) at the University of Washington Hospital in Seattle in March 1960, and some 34 years have elapsed since the United States Congress passed legislation creating the Medicare End Stage Renal Disease Program. Many nephrologists practicing today are unfamiliar with the history of the clinical and political developments that occurred during the 13 years between these 2 dates and that led to dialysis as we know it today in this country. This review briefly describes these events. Clinical developments following introduction of the Teflon shunt by Belding Scribner and Wayne Quinton included empirical observations leading to better understanding of HD and patient management, out-of-hospital dialysis by nurses, bioethical discussions of the problems of patient selection, home HD, improved dialysis technology, intermittent peritoneal dialysis, including automated equipment for home use and an effective peritoneal access catheter, the arteriovenous fistula for more reliable blood access, dialyzer reuse, the first for-profit dialysis units, understanding of many of the complications of treatment, the first considerations of dialysis adequacy, early development of other technologies, and more frequent HD. Political developments began less than 3 years after the first Seattle patient began dialysis, but it took another 10 years of intermittent activities before Congress acted on legislation to provide almost universal Medicare entitlement to patients with chronic kidney disease requiring dialysis or kidney transplantation. PMID- 17336713 TI - Angiotensin and renal disease: the jury is still out. PMID- 17336714 TI - Intravascular ultrasound for the evaluation of therapies targeting coronary atherosclerosis. AB - Many cardiovascular events are clinical manifestations of underlying atherosclerotic disease. The progression of atherosclerosis, traditionally measured by angiography, is predictive of future clinical events and is a valid surrogate marker of cardiovascular (CV) disease. There is growing interest in using novel surrogate end points in clinical trials to expedite the development of new CV therapies. Innovative imaging technologies, such as intravascular ultrasound (IVUS), may carry advantages for the evaluation of coronary atherosclerotic burden and disease progression. Unlike angiography, which displays only the opacified luminal "silhouette," IVUS provides transmural imaging of the entire arterial wall and permits both detection of early-stage atherosclerosis and accurate cross-sectional and even 3-dimensional quantification of plaques. Intravascular ultrasound is now used to guide therapeutic interventions and for diagnostic purposes, primarily for the evaluation of ambiguous lesions and left main coronary artery disease. In addition, clinical studies are using IVUS serially to measure plaque progression, which appears to be related to future CV events. Although the probative force of clinical end point studies still is stronger, IVUS is catching up. Currently, several trials of CV therapies use IVUS-determined plaque progression as the end point. The rationale for using IVUS-based surrogate end points in clinical trials is discussed in the present review. Key advantages of using IVUS-based surrogate end points versus clinical outcome include smaller patient numbers and substantially shorter trial durations; this reduces costs and may expedite the development and testing of new drugs. We expect in the near future a further increase of the use of IVUS-based surrogate end points in trials that evaluate novel CV therapies targeting on coronary atherosclerosis. PMID- 17336715 TI - Is intravascular ultrasound the gold standard surrogate for clinically relevant atherosclerosis progression? AB - Are progressive changes in intravascular ultrasound (IVUS)-derived indexes of plaque size sufficiently predictive of in-trial or future cardiovascular event risk that IVUS can serve as an efficient surrogate for clinical events in coronary disease trials? This question remains unanswered by clinical trials reported to date. Indeed, the answer may well be "yes." Nevertheless, there are enough concerns about the physical limitations, the fundamental assumptions, and the interpretation of the IVUS measurements that the answer cannot be taken for granted. Here, we review the evidence to date, discuss some of the concerns, and compare IVUS results with those of quantitative arteriography. PMID- 17336716 TI - Arterial reactivity in lower extremities is progressively reduced as cardiovascular risk factors increase: comparison with upper extremities using magnetic resonance imaging. AB - OBJECTIVES: Our goal was to investigate whether the association between established cardiovascular risk factors and arterial reactivity differs between the lower and upper extremities. BACKGROUND: Resistance artery reactivity in the arm is associated with cardiovascular risk factors, coronary disease, and events. However, the relationship of lower versus upper extremity vasoreactivity to increasing cardiovascular risk factors has not been determined. METHODS: We studied 82 subjects in 3 groups: 33 young healthy (YH) (21 to 41 years), 30 older healthy (OH) (>50 years), and 19 older type 2 diabetic subjects (OD). We directly measured systolic shear rate, flow, and radius in brachial and femoral arteries at rest and during post-occlusion hyperemia using magnetic resonance imaging. RESULTS: Brachial and femoral systolic shear rate, flow, and radius were similar among the groups at rest. Brachial hyperemic shear rate and hyperemic flow normalized as a function of baseline radius were not statistically different when YH were compared with OH and OH with OD. In contrast, femoral hyperemic shear rate and hyperemic flow normalized to baseline radius were lower in OH than YH (680 +/- 236 s(-1) vs. 843 +/- 157 s(-1), p = 0.001, and 0.84 +/- 0.25 mm(1.27)/s vs. 1.01 +/- 0.16 mm(1.27)/s, p = 0.001) and lower in OD than OH (549 +/- 183 s( 1), p = 0.02, and 0.74 +/- 0.19 mm(1.27)/s, p = 0.046). CONCLUSIONS: Persons with increasing cardiovascular risk factor burden had progressively reduced arterial reactivity in lower but not upper extremities. This may help to explain why atherosclerosis usually develops more severely in legs than in arms, and suggests that legs may be more sensitive than arms for assessing early global atherosclerotic risk. PMID- 17336717 TI - Improved noninvasive assessment of coronary artery bypass grafts with 64-slice computed tomographic angiography in an unselected patient population. AB - OBJECTIVES: In this prospective evaluation we investigated the accuracy of 64 slice computed tomography angiography (CTA) in an unselected but symptomatic patient population for detection of stenoses in bypass grafts when compared with invasive angiography. BACKGROUND: The assessment of significant stenosis in bypass grafts is important for patients with recurrent angina symptoms after bypass surgery. METHODS: High-resolution 64-slice computed tomography (0.6 mm collimation, 330 ms gantry rotation time) and invasive angiography were performed in 138 consecutive patients with a total of 418 bypass grafts. Relevant stenosis was defined as diameter reduction > or =50%. During CTA, arrhythmias were present in 42 (30%) patients who were not excluded from the analysis. RESULTS: The assessment of stenosis or occlusion of bypass grafts resulted in a sensitivity of 97%, specificity of 97%, and positive and negative predictive values of 93% and of 99%, respectively. The diagnostic accuracy for the detection of graft occlusion or stenosis did not differ between arterial and venous grafts. The evaluability of bypass grafts was significantly lower in patients with arrhythmias or with heart rates > or =65 beats/min during scanning. However, in the assessment of evaluable bypass grafts, no significant differences were detected in the diagnostic accuracy in these subgroups. CONCLUSIONS: This large prospective study demonstrates that 64-slice CTA is a reliable method for the assessment of bypass graft patency and stenoses even in an unselected "real world" patient population. PMID- 17336718 TI - Diagnostic accuracy of coronary in-stent restenosis using 64-slice computed tomography: comparison with invasive coronary angiography. AB - OBJECTIVES: This study sought to evaluate the diagnostic accuracy of coronary binary in-stent restenosis (ISR) with angiography using 64-slice multislice computed tomography coronary angiography (CTCA) compared with invasive coronary angiography (ICA). BACKGROUND: A noninvasive detection of ISR would result in an easier and safer way to conduct patient follow-up. METHODS: We performed CTCA in 81 patients after stent implantation, and 125 stented lesions were scanned. Two sets of images were reconstructed with different types of convolution kernels. On CTCA, neointimal proliferation was visually evaluated according to luminal contrast attenuation inside the stent. Lesions were graded as follows: grade 1, none or slight neointimal proliferation; grade 2, neointimal proliferation with no significant stenosis (<50%); grade 3, neointimal proliferation with moderate stenosis (> or =50%); and grade 4, neointimal proliferation with severe stenosis (> or =75%). Grades 3 and 4 were considered binary ISR. The diagnostic accuracy of CTCA compared with ICA was evaluated. RESULTS: By ICA, 24 ISRs were diagnosed. Sensitivity, specificity, positive predictive value, and negative predictive value were 92%, 81%, 54%, and 98% for the overall population, whereas values were 91%, 93%, 77%, and 98% when excluding unassessable segments (15 segments, 12%). For assessable segments, CTCA correctly diagnosed 20 of the 22 ISRs detected by ICA. Six lesions without ISR were overestimated as ISR by CTCA. As the grade of neointimal proliferation by CTCA increases, the median value of percent diameter stenosis increased linearly. CONCLUSIONS: Binary ISR can be excluded with high probability by CTCA, with a moderate rate of false-positive results. PMID- 17336719 TI - Integrating multidetector computed tomography into clinical practice: computed tomography scanning shows its metal. PMID- 17336720 TI - Carvedilol protects better against vascular events than metoprolol in heart failure: results from COMET. AB - OBJECTIVES: We explored whether vascular protection by carvedilol could contribute to its superior effects in the treatment of heart failure (HF) compared with metoprolol tartrate in the COMET (Carvedilol Or Metoprolol European Trial) study. BACKGROUND: Full adrenergic blockade by carvedilol and additional (e.g., antioxidative) properties may lead to vascular protection relative to beta 1 blockade alone, and contribute to its efficacy in HF treatment. METHODS: Three thousand twenty-nine patients with HF due to ischemic (51%) or idiopathic cardiomyopathy (44%) were randomized double-blind to carvedilol (n = 1,511) or metoprolol (n = 1,518) and followed for 58 months. Vascular end points were cardiovascular death, stroke, stroke death, myocardial infarction (MI), and unstable angina. RESULTS: The effect of carvedilol on cardiovascular death improved consistently in subgroups with prespecified baseline variables. Myocardial infarctions were reported in 69 carvedilol and 94 metoprolol patients (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52 to 0.97, p = 0.03). Cardiovascular death or nonfatal MI combined were reduced by 19% in carvedilol (HR 0.81, 95% CI 0.72 to 0.92, p = 0.0009 vs. metoprolol). Unstable angina was reported as an adverse event in 56 carvedilol and in 77 metoprolol patients (HR 0.71, 95% CI 0.501 to 0.998, p = 0.049). A stroke occurred in 65 carvedilol and 80 metoprolol patients (HR 0.79, 95% CI 0.57 to 1.10). Stroke or MI combined occurred in 130 carvedilol and 168 metoprolol patients (HR 0.75, 95% CI 0.60 to 0.95, p = 0.015), and fatal MI or fatal stroke occurred in 34 carvedilol and in 72 metoprolol patients (HR 0.46, 95% CI 0.31 to 0.69, p = 0.0002). Death after a nonfatal MI or stroke occurred in 61 of 124 carvedilol and in 106 of 160 metoprolol patients (HR 0.66, 95% CI 0.48 to 0.90, p = 0.0086). CONCLUSIONS: Carvedilol improves vascular outcomes better than metoprolol. These results suggest a ubiquitous protective effect of carvedilol against major vascular events. PMID- 17336721 TI - Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: the Cardiovascular Health Study. AB - OBJECTIVES: The purpose of this study was to evaluate left ventricular (LV) size and structure in elderly subjects with hypertension (HTN) and heart failure who have a normal ejection fraction (HFNEF) in a large population-based sample. BACKGROUND: The pathophysiology of HFNEF is incompletely understood but is generally attributed to LV diastolic dysfunction with normal or reduced LV diastolic chamber size despite greater than normal filling pressures. METHODS: In the Cardiovascular Health Study (n = 5,888), demographic and clinical characteristics and ventricular structure and function were compared in healthy normal subjects (healthy; n = 499), subjects with HTN but not heart failure (HTN; n = 2,184), and subjects with HTN and HFNEF (HFNEF; n = 167). RESULTS: Subjects with HFNEF were older, more obese, and more often African American than healthy and HTN subjects and had a higher prevalence of diabetes, coronary heart disease, and anemia than HTN subjects. Serum creatinine and cystatin-C were increased in HFNEF subjects. Average LV diastolic dimension was significantly increased in HFNEF subjects (5.2 +/- 0.8 cm) compared with healthy (4.8 +/- 0.6 cm) and HTN (4.9 +/- 0.6 cm) subjects. As a result, average calculated stroke volume (89 +/- 25 ml vs. 78 +/- 20 ml and 80 +/- 20 ml) and cardiac output (6.0 +/- 2.0 l/min vs. 4.8 +/- 1.3 l/min and 5.1 +/- 1.4 l/min) were increased in HFNEF compared with healthy and HTN subjects, respectively. CONCLUSIONS: As a group, HFNEF subjects have increased LV diastolic diameter and increased calculated stroke volume. They also have increased prevalence of multiple comorbidities, including anemia, renal dysfunction, and obesity, that can cause volume overload. These data suggest that extracardiac factors, via volume overload, may contribute to the pathophysiology of HFNEF in the elderly. PMID- 17336722 TI - Left ventricular end-diastolic volume is normal in patients with heart failure and a normal ejection fraction: a renewed consensus in diastolic heart failure. PMID- 17336723 TI - Mortality trends in patients diagnosed with first atrial fibrillation: a 21-year community-based study. AB - OBJECTIVES: The purpose of this study was to assess the mortality trends of atrial fibrillation (AF) in a community. BACKGROUND: Limited data exist regarding the mortality trends of patients diagnosed with first AF. METHODS: A community based cohort of adult residents of Olmsted County, Minnesota, who had electrocardiogram-confirmed first-documented AF in the years 1980 to 2000 were identified and followed to 2004 or death. The primary outcome was all-cause mortality. RESULTS: Of a total of 4,618 residents (mean age 73 +/- 14 years) diagnosed with first AF, 3,085 died during a mean follow-up of 5.3 +/- 5.0 years. Relative to the age- and gender-matched general Minnesota population, the mortality risk was increased (p < 0.0001) with a hazard ratio (HR) of 9.62 (95% confidence interval [CI] 8.93 to 10.32) within the first 4 months and 1.66 (95% CI 1.59 to 1.73) thereafter. Cox proportional hazards modeling showed no change in overall age- and gender-adjusted mortality (HR for the year 2000 vs. 1980: 0.99; 95% CI 0.86 to 1.13; p = 0.84), even after adjustment for comorbidities. In secondary analyses, no changes in mortality were seen for early (within first 4 months) or late (after 4 months) mortality for the entire group or within the subgroup of patients who did not have cardiovascular disease at baseline. CONCLUSIONS: In this cohort of patients newly diagnosed with AF, mortality risk was high, especially within the first 4 months. There was no evidence for any significant changes over the 21 years in terms of overall mortality, early or late mortality, or mortality among patients without pre-existing cardiovascular disease. PMID- 17336724 TI - Anatomical and functional evaluation of pulmonary veins in children by magnetic resonance imaging. AB - Pulmonary vein pathologies often present a diagnostic challenge. Among the different imaging modalities used for the evaluation of pulmonary veins, magnetic resonance is the most comprehensive in assessing anatomy and pathophysiology at the same time. Bright blood cine sequences and contrast-enhanced magnetic resonance angiography outline the course and connections of the pulmonary veins. Phase-contrast velocity mapping measures flow patterns, velocities, and volumes throughout the pulmonary circulation. This paper reviews contemporary utilization of magnetic resonance in the evaluation of pulmonary venous abnormalities in children, based on our experience over the last 5 years and on that of other investigators. We summarize how magnetic resonance imaging enhances our understanding of pulmonary vein physiology and how it can influence the diagnostic approach to children and adults with a pulmonary venous pathology, and we discuss its limitations. PMID- 17336725 TI - Endovascular treatment for superior vena cava occlusion or obstruction in a pediatric and young adult population: a 22-year experience. AB - OBJECTIVES: The purpose of this research was to investigate the causes and symptoms of superior vena cava (SVC) obstruction or occlusion and report on the long-term results of transcatheter therapy. BACKGROUND: Information on transcatheter therapy for SVC obstruction is limited. METHODS: Superior vena cava catheterization interventions between August 1984 and April 2006 were reviewed. Patients were divided into 2 subgroups depending on whether or not they had previously undergone congenital cardiac surgery. RESULTS: Sixty-three patients with median age of 3.7 years (range 1 month to 42 years) and weight of 13.3 kg (range 3 to 114 kg) were treated. Fifty patients (79%) were symptomatic, although only 50% had symptoms suggestive of SVC obstruction. Superior vena cava syndrome was more common in the non-cardiac surgical group (52% vs. 10%, p = 0.001). The mean gradient and SVC diameter improved from 10.8 +/- 5.8 mm Hg to 2.6 +/- 2.2 mm Hg (p < 0.001) and 3.1 +/- 2.7 mm to 9.1 +/- 3.8 mm, respectively (p < 0.001). The obstruction was adequately relieved in all 36 patients receiving stents and in 21 of 27 patients (78%) who had balloon dilation alone. Complications occurred in 12 patients (19%), all of whom had previously undergone cardiac surgery; 10 of these patients were successfully treated in the catheterization laboratory. Freedom from re-intervention did not differ between patients undergoing balloon dilation or stent implantation, but was longer in patients age >5 years at the time of intervention. CONCLUSIONS: Superior vena cava-related symptoms occur in only 50% of patients with hemodynamically significant SVC obstruction. Endovascular therapy is successful in relieving the stenosis and associated symptoms with good long-term results. PMID- 17336727 TI - Evidence-based medicine and clinical judgment: an imaginary divide. PMID- 17336731 TI - The growth hormone receptor in growth. AB - The growth hormone receptor (GHR) is a major effector of Human growth. Functional variants of the GHR include very rare loss-of-function mutations (pathology) and very common polymorphisms (physiology). Recent experimental data have clarified the mechanisms through which mutations of the GHR or Stat5 lead to growth hormone insensitivity and major monogenic growth defects. Recent pharmacogenetic studies support that the response to growth-promoting administration of growth hormone is influenced by exon 3 polymorphism of the GHR. PMID- 17336732 TI - Genetics of growth hormone deficiency. AB - When a child is not following the normal, predicted growth curve, an evaluation for underlying illness and central nervous system abnormalities is required and appropriate consideration should be given to genetic defects causing growth hormone (GH) deficiency. This article focuses on the GH gene, the various gene alterations, and their possible impact on the pituitary gland. Transcription factors regulating pituitary gland development may cause multiple pituitary hormone deficiency but may present initially as GH deficiency. The role of two most important transcription factors, POU1F1 (Pit-1) and PROP 1, is discussed. PMID- 17336733 TI - Factors regulating growth hormone secretion in humans. AB - Growth hormone (GH) secretion is pulsatile in nature in all species. The periodic pattern of GH release plays an important role in transmitting the GH message in a tissue-specific manner. The question of what regulates the pulsatile GH secretion pattern is an issue of not only theoretical interest but of considerable practical importance for designing different GH therapies for a variety of human diseases. This article provides a brief introductory overview of the different regulators of GH secretion and concentrates primarily on human studies. PMID- 17336734 TI - Regulation of growth hormone action by gonadal steroids. AB - Sex steroids modulate growth hormone (GH) secretion and action. Estrogen attenuates GH action in a dose- and route-dependent manner by inhibiting GH regulated endocrine function of the liver. Testosterone amplifies the metabolic action of GH while exhibiting similar but independent effects of its own. The strong modulatory effect of gonadal steroids on GH responsiveness provides insights into the biologic basis of sexual dimorphism in growth, development, and body composition and practical information for the clinical endocrinologist in the treatment of hypopituitary patients. PMID- 17336735 TI - Effects of growth hormone on glucose and fat metabolism in human subjects. AB - This article focuses on in vivo data from tests performed in normal subjects and in patients who had abnormal growth hormone (GH) status. Experimental data in human subjects demonstrate that GH acutely inhibits glucose disposal in skeletal muscle. At the same time GH stimulates the turnover and oxidation of free fatty acid (FFA), and experimental evidence suggests a causal link between elevated FFA levels and insulin resistance in skeletal muscle. Observational data in GH deficient adults do not indicate that GH replacement is associated with significant impairment of glucose tolerance, but it is recommended that overdosing be avoided and glycemic control be monitored. PMID- 17336736 TI - Growth hormone effects on protein metabolism. AB - Growth hormone (GH) has a pivotal role in regulating in vivo protein metabolism. GH enhances protein anabolism at the wholebody level, mainly by stimulating protein synthesis. It remains incompletely understood whether this important GH effect on protein synthesis occurs in all tissues. This effect of GH may be different with acute versus chronic administration. These differences in the GH exposure may have different effects based not only on direct GH stimulation of protein synthesis but also the variable effects at the level of gene transcription that ultimately affect protein metabolism. Other GH effects are likely to be mediated by changes in various metabolites and hormones that also likely differ based on the duration of GH administration. PMID- 17336737 TI - What endocrinologists should know about growth hormone measurements. AB - Determination of human growth hormone (GH) concentration in serum plays a key role in the diagnosis of GH deficiency and GH excess (acromegaly). Methods of measuring GH still lack standardization and show considerable between-method variability. Therefore, correct interpretation of GH test results requires knowledge of measurement techniques and awareness of potential problems in applying recommendations for cut-off values given in the literature. This article focuses on the molecular, structural, and methodologic background of the heterogeneity of assay results and on possible next steps toward standardization. PMID- 17336738 TI - Value of insulin-like growth factor system markers in the assessment of growth hormone status. AB - Insulin-like growth factor-I (IGF-I) has been measured extensively in a variety of clinical settings. Total IGF-I frequently is used to assess the clinical impact of disorders of GH secretion and to monitor patients' response to therapy. It does not have sufficient precision to be used as a stand-alone test in the diagnosis of GH deficiency. Free IGF-I, IGF binding protein-3, or acid-labile subunit may provide useful information regarding GH secretion in specific conditions but are not superior to IGF-I for making the diagnosis of GH deficiency or acromegaly. PMID- 17336739 TI - Growth hormone treatment of non-growth hormone-deficient growth disorders. AB - Although a large body of data on efficacy and safety of growth hormone (GH) treatment for various non-growth hormone-deficient (GHD) growth disorders has accumulated from a combination of clinical trial and postmarketing sources in the last 20 years or more, there remain limitations. Clinical trial data have the advantage of direct comparison of well-matched, randomized patient groups receiving treatment (or not) under comparable conditions and, as such, provide the highest quality evidence of efficacy. Clinical trials, however, are typically too small for any statistically valid assessment for safety, which is more comprehensively addressed using postmarketing data. Consequently, while the efficacy of GH treatment in children with non-GHD growth disorders has been solidly established and, based on the combination of the rigor of the clinical trial data and numerical power of the postmarketing data, no major concerns exist regarding safety, additional long-term data are required. PMID- 17336740 TI - Growth hormone and the transition from puberty into adulthood. AB - With modern growth hormone (GH) replacement algorithms, children with a diagnosis of growth hormone deficiency achieve at the end of pediatric GH treatment an adult height that is on the average in the normal range. Recent experience with GH replacement in young adults with childhood-onset growth hormone deficiency, however, has shown that these patients present with variable degrees of somatic immaturity. As childhood GH treatment is discontinued when final height is attained, attention moves to the phase of somatic development that follows the end of longitudinal growth, called ''transition'', which had been excluded previously from consideration for either pediatric or adult GH replacement. This article reviews the changes taking place during this phase of development and their relevance for the attainment of adult body maturation. The critical role of GH in this process is described. PMID- 17336741 TI - Management of adult growth hormone deficiency. AB - The management of adults who have severe growth hormone deficiency (GHD) includes its recognition in susceptible patients, including all subjects who have any form of hypothalamic pituitary disorder. This article also focuses on the overall management of adults who have hypopituitarism and severe GHD. This includes aspects of diagnosis and management of growth hormone replacement therapy and the current status of its long-term safety. Some special circumstances, including the pregnant woman who has hypopituitarism, are discussed. PMID- 17336742 TI - Quality of life in growth hormone deficiency and acromegaly. AB - Quality of life (QoL) has emerged as an end point in the evaluation of adults with growth hormone deficiency and acromegaly. QoL is measured with questionnaires designed to be used in general population or any kind of disease (generic) or aimed at the specific dimensions affected in a determined condition; these latter ones are more likely to identify the impairments caused by the underlying disease and the benefits of treatment. QoL, which is severely impaired in adults with growth hormone deficiency, improves and normalizes after growth hormone replacement therapy and this effect is maintained over several years. Acromegalic patients also exhibit severe impairment of QoL, which despite improvement after successful therapy still remains below the reference values of normal population. QoL in these chronic endocrine diseases can be used as an measure for clinical and therapeutic evaluation. PMID- 17336743 TI - Growth hormone supplementation in the elderly. AB - The imminent rapid increase in numbers of aging adults will significantly impact society and the health system in the coming years. The imperative is to allow older adults to maintain their independence and health for as long as possible and to prevent the ravages of chronic diseases and disabilities or the development of frailty. Significant hormonal changes are observed with aging (eg, decline in growth hormone [GH]), and strikingly similar changes in body composition are seen in GH-deficient adults and during aging. This article reviews some of the studies describing the effects of GH and GH secretagogues on body composition and functionality in the elderly. In addition, safety concerns and the need for further controlled studies of these therapies in the elderly are discussed. PMID- 17336744 TI - Growth hormone treatment and cancer risk. AB - Increasing numbers of children receive growth hormone (GH) to treat a range of growth disorders, including those rendered GH deficient (GHD) by tumors or their treatment. Young persons with persistent growth hormone deficiency (GHD) and adults with severe GHD are also eligible to receive GH treatment. As in vitro and in vivo studies and epidemiologic observations provide some evidence that the GH- insulin like growth factor-I (IGF-I) axis is associated with tumorigenesis, it is important to assess, in practice, the incidence of tumors related to GH treatment. Reassuringly, surveillance studies in large cohorts of children and in smaller cohorts of adults indicate that GH is not associated with an increased incidence of tumor occurrence or recurrence. Nevertheless, all children who have received GH, in particular cancer survivors and those receiving GH in adulthood, should be in surveillance programs to assess whether an increased rate od late onset and rare tumours may occur. PMID- 17336745 TI - The time for 3D. PMID- 17336747 TI - 3D echocardiography: a review of the current status and future directions. PMID- 17336748 TI - Non-Doppler two-dimensional strain imaging by echocardiography--from technical considerations to clinical applications. AB - During the past several years, strain and strain rate imaging have emerged as a quantitative technique to accurately estimate myocardial function and contractility. Non-Doppler, 2-dimensional (2D) strain imaging is a new echocardiographic technique for obtaining strain and strain rate measurements. It analyzes motion by tracking speckles in the ultrasonic image in two dimensions. Current available software allows spatial and temporal image processing with recognition and selection of such elements on ultrasound image. The geometric shift of each speckle represents local tissue movement. By tracking theses speckles, 2D tissue velocity, strain, and strain rate can be calculated. Non Doppler 2D strain imaging is simple to perform. It requires only one cardiac cycle to be acquired; further processing and interpretation can be done after image data acquisition. Because it is not based on tissue Doppler measurements, it is angle independent. Data regarding accuracy, validity, and clinical application of non-Doppler 2D strain imaging are rapidly accumulating. This technique may prove to be of significant clinical value, enabling rapid and accurate assessment of global and segmental myocardial function. PMID- 17336749 TI - Risk stratification using stress echocardiography: incremental prognostic value over historic, clinical, and stress electrocardiographic variables across a wide spectrum of bayesian pretest probabilities for coronary artery disease. AB - OBJECTIVES: We sought to evaluate the risk stratification ability and incremental prognostic value of stress echocardiography over historic, clinical, and stress electrocardiographic (ECG) variables, over a wide spectrum of bayesian pretest probabilities of coronary artery disease (CAD). BACKGROUND: Stress echocardiography is an established technique for the diagnosis of CAD. However, data on incremental prognostic value of stress echocardiography over historic, clinical, and stress ECG variables in patients with known or suggested CAD is limited. METHODS: We evaluated 3259 patients (60 +/- 13 years, 48% men) undergoing stress echocardiography. Patients were grouped into low (<15%), intermediate (15-85%), and high (>85%) pretest CAD likelihood subgroups using standard software. The historical, clinical, stress ECG, and stress echocardiographic variables were recorded for the entire cohort. Follow-up (2.7 +/- 1.1 years) for confirmed myocardial infarction (n = 66) and cardiac death (n = 105) was obtained. RESULTS: For the entire cohort, an ischemic stress echocardiography study confers a 5.0 times higher cardiac event rate than the normal stress echocardiography group (4.0% vs 0.8%/y, P < .0001). Furthermore, Cox proportional hazard regression model showed incremental prognostic value of stress echocardiography variables over historic, clinical, and stress ECG variables across all pretest probability subgroups (global chi2 increased from 5.1 to 8.5 to 20.1 in the low pretest group, P = .44 and P = .01; from 20.9 to 28.2 to 116 in the intermediate pretest group, P = .47 and P < .0001; and from 17.5 to 36.6 to 61.4 in the high pretest group, P < .0001 for both groups). CONCLUSIONS: A normal stress echocardiography portends a benign prognosis (<1% event rate/y) in all pretest probability subgroups and even in patients with high pretest probability and yields incremental prognostic value over historic, clinical, and stress ECG variables across all pretest probability subgroups. The best incremental value is, however, in the intermediate pretest probability subgroup. PMID- 17336750 TI - Short-term risk stratification with accelerated high-dose dipyridamole stress echocardiography: follow-up into 301 consecutive outpatients. AB - AIM: This study aimed to assess the short-term predictive value of a pharmacologic stress echocardiography test performed with accelerated high-dose dipyridamole (0.84 mg/kg over 6 minutes). METHODS: In all, 301 patients (161 men, mean age 61.41 +/- 11.62 years) were scheduled for accelerated high-dose dipyridamole stress test. A total of 22 tests were interrupted prematurely because of side effects (overall feasibility 92.7%). The patients were followed up for nonfatal myocardial infarction, unstable angina, myocardial revascularization, and sudden death at first and third months and each 6 months (maximum 18 months). RESULTS: A positive echocardiographic response was found in 25 patients. Six patients with negative stress test experienced events. Eight patients with positive stress test went to coronary revascularization procedure. Negative predictive value was 97.8%, positive predictive value was 32%, sensitivity was 57%, and specificity was 94%. CONCLUSIONS: Risk stratification with accelerated high-dose dipyridamole stress echocardiography is effective. A negative test predicts favorable short-term cardiovascular prognosis. PMID- 17336751 TI - Prognostic significance of akinesis becoming dyskinesis during dobutamine stress echocardiography. AB - BACKGROUND: Akinesis becoming dyskinesis (AKBD) at high-dose dobutamine stress echocardiography (DSE) has been disregarded as a marker of myocardial ischemia. However, its prognostic significance is unknown. OBJECTIVES: We sought to assess the long-term outcome of patients with AKBD during DSE. METHODS: A total of 731 patients (age 62 +/- 15 years, 628 men) with two or more akinetic left ventricular segments at rest underwent DSE and were followed up for a mean period of 5 +/- 2.7 years. The end points considered during follow-up were hard cardiac events (cardiac death and nonfatal myocardial infarction) and heart failure. RESULTS: Dyskinesis in two or more segments at peak stress developed in 60 patients (8%). Resting wall-motion score index was 2.6 +/- 0.56 in patients with AKBD versus 2.3 +/- 0.55 in patients without AKBD (P = .0002). Ischemia occurred in 197 patients (27%). During follow-up, 254 patients (35%) developed hard cardiac events and 204 patients (28%) developed heart failure. In all, 226 patients (31%) died of various causes (cardiac death in 172 patients). The annualized hard cardiac event rate was 11% in patients with AKBD and 6% in patients without (P = .03). The incidence of heart failure was significantly higher in patients with AKBD than without (47% vs 26%, P < .001). Independent predictors of hard cardiac events were age (hazard ratio [HR] 1.03 [confidence interval {CI} = 1.01-1.04]), previous myocardial infarction (HR 1.4 [CI = 1.1 1.9]), diabetes mellitus (HR 1.8 [CI = 1.3-2.5]), resting wall-motion score index (HR 1.11 [CI = 1.01-1.04]), and AKBD (HR 1.6 [CI = 1.1-2.4]). CONCLUSION: AKBD at peak DSE is associated with increased risk of cardiac events in patients with akinetic segments at baseline echocardiogram. PMID- 17336752 TI - Significance of additional ST segment elevation in patients with no reflow after angioplasty for acute myocardial infarction. AB - OBJECTIVES: We sought to evaluate the incidence, timing, and clinical significance of additional increase in ST segment elevation (ST-SE) in patients showing no reflow after angioplasty for acute myocardial infarction. METHODS: We studied 26 patients with acute myocardial infarction showing myocardial contrast echocardiography no reflow after successful angioplasty. Baseline and 6-month 2 dimensional echocardiograms were obtained in 21 surviving patients. RESULTS: After angioplasty, 13 patients showed greater than 30% additional increase in ST SE (group 1), whereas 13 did not (group 2). Baseline clinical, echographic, and angiographic characteristics, and 6-month patency and restenosis rate, were similar between the two groups. From baseline to 6 months, a similar global and regional systolic function was found between the two groups, whereas a higher increase in left ventricular end-diastolic volume occurred in group 1 (135 +/- 45 vs 168 +/- 42 mL, P = .033). The additional increase in ST-SE was not associated with more severe microvascular damage (myocardial contrast echocardiography score index: 0.14 +/- 0.26 vs 0.22 +/- 0.27), higher peak creatine kinase value (4888 +/- 2533 vs 3109 +/- 2055 U/L, P = .061), higher incidence of left ventricular remodeling (73% vs 60%, P = .537), or worse outcome (26 +/- 24 months) such as death (15% vs 23%, P = .619), hospitalization for heart failure (8% vs 23%, P = .277), or reinfarction (8% vs 0%, P = .308). CONCLUSIONS: Our data show that in patients showing no reflow after angioplasty a transient additional increase in ST-SE occurs in half of patients. The prognostic value of additional increase in ST-SE remains uncertain in the era of primary angioplasty. PMID- 17336753 TI - The noninvasive evaluation of exercise-induced changes in pulmonary artery pressure and pulmonary vascular resistance. AB - BACKGROUND: During exercise, pulmonary artery systolic pressure (PASP) may increase. The purpose of this study was to examine the responses of PASP and pulmonary vascular resistance by Doppler echocardiography during exercise in conditioned athletes and in patients with pulmonary disease. METHODS: Fifteen participants in each group were evaluated using Doppler echocardiography at rest and during recumbent bicycle exercise. PASP was calculated using 4 times the tricuspid regurgitant velocity squared (TRV)2 and a surrogate for pulmonary vascular resistance was calculated using the equation: pulmonary vascular resistance = TRV/right ventricular outflow tract time-velocity integral. RESULTS: During exercise, PASP increased in both groups with higher values achieved by patients with pulmonary conditions (54.8 vs 70.6 mm Hg, P = .009). At baseline the ratio TRV/right ventricular outflow tract time-velocity integral was 0.2 or less in both the athlete and pulmonary groups. During exercise, the ratio of TRV/right ventricular outflow tract time-velocity integral remained less than 0.2 in the athletes and increased more than 0.2 in the pulmonary group. CONCLUSION: Doppler echocardiography can be used to discriminate a flow- versus resistance mediated mechanism for exercised-induced increase in PASP. PMID- 17336754 TI - Relation of ultrasound morphologic characteristics of central pulmonary artery thromboemboli to their ex vivo lysibility. AB - BACKGROUND: Ultrasound morphology of massive central pulmonary artery thromboemboli (TE) is an independent predictor of 30-day mortality. The aim of this study was to asses ex vivo lysibility of morphologically different TE. METHODS: Forty-five central pulmonary artery TE, collected at autopsies, were divided into hypoechoic (group A) and hyperechoic (group B) categories. TE were lysed with alteplase in a perfusing system simulating pulmonary circulation for 1 hour. RESULTS: The grey scale mean of thrombi in group B was higher compared with group A (64 +/- 7 vs. 38 +/- 7, respectively, P < .01). Spontaneous lysis in group A did not differ compared with group B (2.2% +/- 0.5% vs. 2.1% +/- 0.4%, P = .4). After incubation with alteplase, the weight of TE was reduced more in group A than in group B (16% +/- 2% vs. 11% +/- 2%, P < .001). The grey scale mean negatively correlated with the percentage of TE weight reduction (0.768) (P < .001). CONCLUSION: Ultrasound morphology of TE from central pulmonary arteries correlates significantly with ex vivo lysibility. Hypoechoic TE are more susceptible to thrombolysis than hyperechoic TE. PMID- 17336755 TI - Laptop-sized echocardiography machine versus full-sized top-of-the-line machine: a comparative study. PMID- 17336756 TI - Esophageal overtube facilitation of transesophageal echocardiography in patients with previously difficult esophageal intubation. AB - BACKGROUND: In upper endoscopy, overtubes protect the hypopharynx and esophagus in patients requiring multiple esophageal intubations. Transesophageal echocardiography (TEE) is frequently used in general cardiology practice to provide high-resolution, real-time images of cardiac structures that are often not visualized by transthoracic imaging alone. Patients with a history of esophageal disorders or difficult esophageal intubations may have increased risk for complications from the echoprobe. An esophageal overtube may facilitate TEE in such patients. OBJECTIVE: We sought to evaluate the usefulness of upper endoscopy with placement of an esophageal overtube to facilitate TEE in patients with prior difficult esophageal intubations. METHODS: We performed upper endoscopy, followed by placement of an esophageal overtube, in 4 patients who had an unsuccessful intubation with the TEE probe. The endoscopic procedures were successfully completed, thus, allowing for uneventful subsequent TEE. CONCLUSIONS: Upper endoscopy with placement of an esophageal overtube may allow for safe successful completion of TEE in patients with previously unsuccessful blind esophageal intubation. PMID- 17336757 TI - Arginine 16 glycine beta2-adrenoceptor polymorphism and cardiovascular structure and function in patients with heart failure. AB - The beta2/beta1 adrenoceptor ratio increases in congestive heart failure (CHF), making the heart relatively more dependent on inotropic, lusitropic, and chronotropic stimulation by the beta2-adrenergic receptor (ADRB2). In healthy human beings, those who are homozygous for arginine (Arg) at amino acid 16 of the ADRB2 have reduced receptor function when compared with individuals homozygous for glycine (Gly) at this position. The cardiovascular effects of the Arg16Gly polymorphism of the ADRB2 in CHF are not well understood. The aim of this study was to examine the influence of common polymorphisms of the ADRB2 on cardiovascular structure and function in patients with CHF. Echocardiography, neurohormonal assays, and exercise tests were performed in 68 healthy individuals and 95 patients with CHF. All of the patients with CHF were stable, New York Heart Association class II to III, of ischemic or nonischemic cause, with an ejection fraction of 40% or less. Of the patients with CHF, 16 were Arg/Arg, 36 were Arg/Gly, and 43 were Gly/Gly at amino acid 16. In those without CHF, the Arg16Gly polymorphism of the ADRB2 had no effect on cardiovascular function. In contrast, in CHF, Arg/Arg homozygotes had higher plasma norepinephrine and atrial natriuretic peptide levels, greater left atrial diastolic dimension, higher peak velocity of early/late diastolic filling ratio, and shorter deceleration time compared with Gly16 homozygotes. Furthermore, Arg16 homozygotes had reduced exercise tolerance compared with Gly16 homozygotes (evidenced by shorter exercise duration and lower peak oxygen consumption per unit time), and a lesser chronotropic response to exercise. In patients with CHF, but not in demographically matched healthy persons, the Arg16Gly polymorphism of the ADRB2 exerts important effects on cardiovascular structure and function, neurohormonal activation, and exercise tolerance. PMID- 17336758 TI - Circumferential versus longitudinal systolic function in patients with hypertension: a nonlinear relation. AB - BACKGROUND: Depressed circumferential midwall performance and impaired left ventricular (LV) longitudinal function are both early markers of LV systolic dysfunction in patients with hypertension. The relation between midwall and longitudinal indices in these patients has never been analyzed. METHODS: In 126 patients with hypertension, midwall fractional shortening (mFS), stress-corrected mFS, M-mode left atrioventricular plane displacement, and tissue Doppler-derived peak mitral annular systolic velocity were determined. RESULTS: Regression analysis showed that the relations of midwall indices to atrioventricular plane displacement and mitral annular systolic velocity were all nonlinear. Reductions in atrioventricular plane displacement or mitral annular systolic velocity within their higher ranges corresponded to relatively smaller decreases in mFS and stress-corrected mFS. Relative wall thickness was the strongest determinant of the relative efficiency of circumferential and longitudinal LV contraction. CONCLUSION: The relation between circumferential midwall and longitudinal function in patients with hypertension is nonlinear and dependent on LV geometry. In these patients, systolic impairment occurs earlier in longitudinal than circumferential performance. PMID- 17336759 TI - Prospective evaluation of aortic dimensions in Turner syndrome: a 2-dimensional echocardiographic study. AB - BACKGROUND: The prevalence of aortic disease, including dilatation of the proximal aorta, is higher in patients with Turner syndrome (TS) compared with healthy female control subjects, but there are no data regarding the prospective evaluation of aortic dimensions in this syndrome. OBJECTIVE: This study was undertaken to assess the: (1) prevalence of aortic root (AR) and proximal thoracic aorta enlargement by 2-dimensional echocardiography; and (2) evolution of aortic diameters over time. METHODS: In all, 78 patients with kariotypically proven TS (mean age 21.5 +/- 9 years) underwent a 2-dimensional echocardiographic study of the proximal thoracic aorta at baseline and yearly thereafter, during a median follow-up period of 37 months (25th-75th percentile: 25-51). We investigated the AR, sinotubular aortic junction, and tubular portion of the ascending thoracic aorta. Linearity of the relationship between AR dimensions and body surface area allowed us to use Roman nomograms to identify patients with or without an enlarged AR. RESULTS: At baseline, 62 of 78 patients (80%) presented normal AR dimensions compared with 16 of 78 (20%) with AR dilatation. Mean AR diameter was 24.5 +/- 3.6 versus 30.9 +/- 4.6 mm (P = .0001), sinotubular aortic junction was 18.0 +/- 4.0 versus 21.7 +/- 5.2 mm (P = .015), and ascending thoracic aorta was 21.1 +/- 4.1 versus 26.6 +/- 6.0 mm, respectively (P = .003). The incidence of AR dilatation was similar in patients younger than 18 years or 18 years and older. During follow-up, we observed a similar significant, albeit minor, increase in aortic diameters in all patients. However, the absolute entity of this increase was not clinically relevant. Lymphedema at birth was the only significant clinical variable observed more frequently in patients with AR enlargement compared with those with normal AR. CONCLUSIONS: Proximal aortic dimensions in patients with TS did not change rapidly in our medium-term follow up study. The progression of AR dimensions was similar in patients with (20%) or without baseline AR dilatation. Age did not affect the pattern and evolution of aortic disease in TS. PMID- 17336760 TI - Relation of proximal aorta stiffness to left ventricular diastolic function in patients with end-stage renal disease. AB - AIM: We examined the relationship between proximal aortic stiffness and left ventricular (LV) diastolic function in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS: We studied 99 patients with ESRD with preserved LV ejection fraction greater than 50% and 83 controls. We assessed the aorta stiffness by measuring the pulse wave velocity (PWV) in the proximal aorta (PWVr) using a novel echo application and in the descending aorta (PWVcf) using a foot to-foot method. Patients were classified according to LV diastolic filling pattern into normal, delayed relaxation, pseudonormal, and restrictive filing pattern groups. RESULTS: Patients with ESRD had increased PWVr, PWVcf, and LV mass index (LVMI) compared with controls (all P < .0001). Patients with advanced diastolic dysfunction showed increased PWVr (P < .001) and PWVcf (P = .007) compared with those with mild diastolic dysfunction. PWVr was correlated to PWVcf (r = 0.74, P < .001) in patients with ESRD. Multivariate linear regression analysis revealed that PWVr was independently correlated to both LVMI and LV diastolic filling pattern. CONCLUSIONS: Increased LVMI, advanced LV diastolic dysfunction, and generalized aortic stiffening were observed in patients with ESRD. Proximal aorta stiffness is associated with both increased LVMI and advanced LV diastolic dysfunction in those patients. PMID- 17336761 TI - New monodimensional transthoracic echocardiographic sign of left atrial appendage function. PMID- 17336762 TI - Coronary artery fistula with anomalous coronary artery origin: a case report. AB - Congenital anomalies of the coronary arteries occur in 0.2% to 1.2% of the general population. Most coronary artery anomalies are found incidentally during angiographic evaluation for other cardiac diseases. We describe the case of a young woman presenting with chest discomfort and fatigue where echocardiography identified a coronary artery fistula. Successful embolization of the coronary artery fistula was performed. To our knowledge, this is a unique case of an anomalous coronary artery and a fistulous anomaly in the same patient. This report describes the echocardiographic diagnosis, and the feasibility of a transcatheter management decision to avoid cardiopulmonary bypass in a patient in whom blood products are contraindicated. PMID- 17336763 TI - Substantial myocardial abscess in an immunocompromised patient: fatal outcome after coagulase-negative Staphylococcal native valve infection. AB - We present the fatal case of a patient with a 3-month history of malaise, fatigue, low-grade fever and increasing signs of heart failure. Because of a sudden loss of sight and elevated sedimentation rate, arteritis temporalis was mistakenly suspected and treatment with high dose prednisolone was initiated. Five weeks later the patient presented with worsening of symptoms and septicemia with coagulase negative staphylococcus (CoNS). Transesophageal echocardiography revealed a left atrial mass and stenosis of a severely calcified aortic valve, but no definite vegetations. The diagnose of infectious endocarditis was established during surgery, with the discovery of an abscess cavity at the non coronary cusp of the aortic valve and by the growth of the same CoNS from tissue samples from the abscess in the atrial wall, as had been found in blood cultures. A systolic murmur was heard initially, but echocardiography was not performed until 5 weeks later and illustrates the pivotal role of echocardiography in the early diagnosis and treatment of infectious endocarditis. PMID- 17336765 TI - Management of agitation in the acute psychotic patient--efficacy without excessive sedation. AB - Rapid-acting intramuscular (IM) formulations of atypical antipsychotics offer a significant advance over IM haloperidol in the short-term management of acute schizophrenic episodes. Several short-term open-label randomised studies, typically enrolling two- to three-hundred patients, have compared an atypical antipsychotic with haloperidol. These studies show that IM ziprasidone, IM olanzapine and IM aripiprazole are at least as effective and better tolerated than IM haloperidol, with lower extrapyramidal side effects. Successful transitions from an IM to oral formulation of the same agent have been performed in double-blind randomised trials assessing haloperidol, olanzapine, ziprasidone and aripiprazole. Avoiding over-sedation is now recognised as important, and randomised clinical trial data indicate that oral ziprasone, quetiapine, and IM olanzapine have high dose-related sedative potential while oral risperidone and IM aripiprazole have low sedative potential. In summary, IM formulations of atypical antipsychotics are recommended as first-line treatment of acute agitation with subsequent transition to an oral formulation of the same agent for ongoing management. PMID- 17336764 TI - Risk factors for schizophrenia--all roads lead to dopamine. AB - Schizophrenia is a debilitating disease of major public health importance, the incidence of which shows prominent worldwide variation (up to fivefold) and is about 40% greater in men than in women. Furthermore, epidemiological studies have shown that the incidence is higher among those who grow up in urban areas and among migrants. Recent evidence indicates that, although the neurochemical origins of schizophrenia do not necessarily lie in dopamine dysregulation, this operates as the final common pathway underlying positive psychotic symptoms and may also play a role in negative and cognitive symptoms. The last few years have seen the development of a plausible model in which schizophrenia is seen as the consequence of the actions of a number of component causes, such as genes or early environmental hazards that subtly alter subsequent neurodevelopment, thereby predisposing the child to later dopamine dysregulation. PMID- 17336766 TI - The stable patient with schizophrenia--from antipsychotic effectiveness to adherence. AB - Long-term treatment of stable schizophrenia focuses on treatment effectiveness, addressing direct efficacy plus treatment adherence, treatment burden, and impact on factors such as weight gain. With the introduction of atypical antipsychotics such as aripiprazole, reduced side effects may lead to improved long-term treatment. The Clinical Trials of Intervention Effectiveness (CATIE) study where 1500 patients were randomised to atypical antipsychotics (olanzapine, quetiapine, risperidone, ziprasidone), or the typical antipsychotic drug perphenazine showed high discontinuation rates of 74% after 18 months, but extrapyramidal side effects were lower after atypical antipsychotic treatment compared with perphenazine. Twenty-six weeks of aripiprazole treatment, assessed in 284 patients in the Schizophrenia Trial of Aripiprazole (STAR) showed that aripiprazole had similar discontinuation rates to the atypical antipsychotics standard of care. In the CATIE study, weight gain was common during treatment. In contrast, STAR demonstrated a favourable weight profile for aripiprazole, with a mean weight loss of 0.41 kg. Results from these naturalistic trials help define the effectiveness of atypical antipsychotics for long-term treatment. PMID- 17336767 TI - The long term--maximising potential for rehabilitation in patients with schizophrenia. AB - Patients with schizophrenia show low employment rates and low Quality of Life (QoL), and rehabilitation aims to maximise daily functioning, improve social interactions, and develop employment prospects. Evaluation of long-term treatment effectiveness should address these issues. Choice of medication can influence patient compliance and adverse experience of side effects may act as a barrier to rehabilitation. The Schizophrenia Trial of Aripiprazole (STAR), in which patients were randomised to receive 26 weeks of the atypical antipsychotic, aripiprazole (n=284) or standard of care medication (n=271) showed that aripiprazole demonstrated significantly better effectiveness in terms of Investigator Assessment Questionnaire (IAQ) total score. Like other atypical antipsychotic agents, aripiprazole shows a low rate of extrapyramidal adverse events. In addition, unlike the majority of other agents, aripiprazole treatment has a low risk of weight gain, translating into health-related QoL benefits. In summary, newer, atypical agents may improve efficacy, patient satisfaction, and aid long term rehabilitation. PMID- 17336770 TI - Neurophysiological classification of myoclonus. AB - Myoclonus can be diagnosed and classified mainly based on clinical features. Neurophysiologic studies help confirm clinical diagnosis and classification, and understand underlying physiological mechanisms. The neurophysiologic classification of myoclonus is mainly based on surface EMG (individual EMG patterns, muscle spatial distribution and time sequence of muscle activation), EEG, EEG/EMG relationships (jerk-locked back-averaging, cortico-muscular coherence), somatosensory evoked potentials, and long-loop reflexes. Paired stimulation evoked response/long loop reflex and jerk-locked evoked responses evaluate the excitability changes of the primary somatosensory cortex. Transcranial magnetic stimulation can evaluate the excitability state of the primary motor cortex. PMID- 17336772 TI - Neurophysiology of myoclonus. AB - Myoclonus may be generated by any area in the central nervous system. Finding its generator is helpful in the diagnostic process. Although clinical features have to be carefully analyzed as they may give a first idea, neurophysiologic study of myoclonus provides the most important clues for the determination of the generator. Surface electromyography (EMG) allows analyzing the recruitment order in generalized myoclonus, thereby suggesting either a cortical, brainstem, or spinal origin. It also reveals whether myoclonus is positive (jerks that are caused by muscle activation) or negative (jerks that are caused by brief muscle inhibition). In non-generalized myoclonus the EMG burst duration gives an idea of the level of the generator. Repetitive peripheral nerve stimulation is required to record somatosensory evoked potentials (SEPs) as well as long latency reflexes (LLR), especially the C reflex. The presence of giant cortical SEPs is an indirect argument for cortical myoclonus. Similarly the existence of LLR at rest orientates towards cortical reflex (sensitive to sensory stimuli) myoclonus. Finally EEG-EMG polygraphy is the only test which is able to prove directly the cortical origin of myoclonus. This is the case when focal cortical events precede myoclonus with a fixed delay. These premyoclonic cortical potentials may either be seen directly on raw recordings or require the use of jerk-locked back averaging (JLBA). This technique allows the averaging of the EEG prior to myoclonus onset (as determined by EMG) in order to reveal a premyoclonic spike that otherwise would remain undetected in the global EEG. PMID- 17336771 TI - Some genetic and biochemical aspects of myoclonus. AB - Can a gene defect be responsible for the occurrence in an individual, at a particular age, of such a muscle twitch followed by relaxation called: "myoclonus" and defined as sudden, brief, shock-like movements? Genetic defects could indeed determine a subsequent cascade of molecular events (caused by abnormal encoded proteins) that would produce new aberrant cellular relationships in a particular area of the CNS leading to re-built "myoclonogenic" neuronal networks. This can be illustrated reviewing some inherited neurological entities that are characterized by a predominant myoclonic picture and among which a clear gene defect has been identified. In the second part of this chapter, we will also propose a new point of view on how some structural genes could, under certain conditions, when altered, produced idiopathic generalized epilepsy with myoclonic jerks, taking juvenile myoclonic epilepsy (JME) and the myoclonin (EFHC-1) gene as examples. PMID- 17336773 TI - Myoclonus and transcranial magnetic stimulation. AB - The neural dysfunction at the origin of myoclonus may locate at various anatomical levels within the central nervous system, including the motor cortices. Transcranial magnetic stimulation (TMS) can be used to assess the balance between inhibitory and excitatory processes involved in the regulation of motor cortex activity and thereby, may be of value to determine the pathophysiological mechanisms of myoclonus. Using paired-pulse paradigms with various interstimulus intervals, TMS studies showed that intracortical inhibition (ICI) was reduced in progressive myoclonic epilepsy (PME). In contrast, ICI was decreased only for short interstimulus intervals in patients with juvenile myoclonic epilepsy (JME). Transcallosal inhibition and sensorimotor integration were also both altered in PME but not in JME. Actually, the loss of inhibitory regulation within the central nervous system might represent an intrinsic mechanism of myoclonus, whether of epileptic origin or not. Finally, the other TMS parameters of excitability (motor threshold, silent period, intracortical facilitation) were found normal in most cases of myoclonus. According to these observations, it was quite conceivable that the application of repetitive trains of TMS (rTMS) at inhibitory low-frequency (around 1 Hz) might be able to relieve myoclonus by restoring ICI. A few reported cases illustrate the efficacy of low frequency rTMS to alleviate myoclonic symptoms. Therapeutic-like perspectives are opened for rTMS in these forms of myoclonus that are related to motor cortical hyperexcitability secondary to the loss of ICI. PMID- 17336774 TI - Proprioception and myoclonus. AB - This review focuses on sensory information originating from muscle spindles and its role in proprioception and motor control. The first part reminds of the structural and functional properties of these muscle mechanoreceptors, with arguments for an independent fusimotor command, i.e. the gamma-motoneurons, that would regulate spindle mechanical sensitivity in keeping with the requirements of ongoing motor action. The possibility that dysfunction of the fusimotor system might be responsible for clinical signs is discussed with respect to the hyperexcitability of the sensorimotor cortex that is observed in myoclonus of cortical origin. What is known about the spindle afferents projections into the spinal cord and about the dysfunction of the spinal sensorimotor networks in patients with neurological disorders, is put together in the second part. It is stressed on the significant complexity of the monosynaptic reflex in spite of its "simple" organization. The monosynaptic reflex constitutes the only possible way for testing the excitability of motoneurons and spinal networks. This method is extensively used clinically to examine changes in the nervous system with diseases. When studying changes from the norm, it is important to understand how the reflex functions in neurologically normal conditions. Different mechanisms such as pre-synaptic inhibition, post-activation depression and motoneuronal intrinsic properties are reviewed as they may induce changes in reflex amplitude and have therefore consequences for interpretation of spinal excitability. PMID- 17336775 TI - Symptomatic myoclonus. AB - A huge number of neurological disorders are associated with myoclonus. This paper describes these disorders whose diagnosis partly relies on the presence of myoclonus. The diagnostic approach is related to certain clinical features of myoclonus, which, after their integration in the clinical context, help orientate towards diagnosis. Myoclonus is frequent during dementia. Although its presence is well-known to take part in the diagnosis of Creutzfeldt-Jakob disease (CJD), myoclonus can also be present to a significant degree in Alzheimer's disease and Lewy body dementia (LBD), which raises a diagnostic issue. Both its clinical and electrophysiological features may help differential diagnosis, given that myoclonus with fast-evolving dementia and focal neurological signs should favor the diagnosis of CJD. Myoclonus in a context of progressive ataxia suggests one clinical form of the Ramsay-Hunt syndrome (progressive myoclonic ataxia, PMA), whose most frequent causes are: coeliac disease, mitochondriopathies, some spino cerebellar degenerations, and some late metabolic disorders. In addition to ataxia and myoclonus, the presence of opsoclonus directs diagnosis toward the opsoclonus-myoclonus syndrome (OMS), whose origin, in adult, is idiopathic or paraneoplastic. Palatal tremor (myoclonus) with ataxia may represent either a sporadic pattern, which often reflects the evolution of degenerative or lesional disorders, or a familial pattern in some degenerative affections or metabolic diseases. Of more recent knowledge is the association of progressive ataxia, myoclonus, and renal failure, which corresponds to a recessive autosomic disease. In a context of encephalopathy, myoclonus is frequent in metabolic or hydro electrolytic disorders, and in brain anoxia. One should distinguish these various forms of myoclonus which may occur in the acute post-anoxic phase, from those occurring as sequels at a later stage, i.e. the Lance and Adams syndrome whose clinical aspects are also multiple. Myoclonus is less frequent during toxic or drug exposures. Irrespective of its acute or insidious onset, Hashimoto's encephalopathy is accompanied by myoclonus and tremor. Myoclonus may also be present during encephalic and/or spinal infectious disorders. Myoclonus with focal neurological signs may be observed in thalamic lesions, responsible for unilateral asterixis or unilateral myoclonus superimposed on dystonic posture. Segmental spinal myoclonus or propriospinal myoclonus may be associated with several spinal-cord disorders. Myoclonus associated with peripheral nerve lesions is exceptional or even questionable for some of these. PMID- 17336776 TI - Myoclonus and extrapyramidal diseases. AB - Parkinsonism or dystonia are associated with myoclonus in several extrapyramidal diseases. Although the latter symptom is not always prominent, stimulus sensitive, distal, or focal reflex myoclonus is frequently observed. This review will consider the clinical and electrophysiological features of myoclonus in Parkinson's disease, multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, Huntington's disease, dentatorubral pallidoluysian atrophy, Lewy body dementia, and myoclonus with dystonia. The evidence of a long-latency reflex response, the presence of giant somatosensory evoked potentials, and the demonstration of a back-averaged premyoclonus focal cortical EEG activity often lead to classify myoclonus as a cortical phenomenon. However, a subcortical origin cannot always be ruled out. PMID- 17336777 TI - Myoclonus and movement disorders. AB - Myoclonus is a movement disorder characterized by the occurrence of an involuntary abrupt muscle contraction causing a sudden unexpected jerk. Many other movement disorders can present with the same jerky, shock-like appearance. This paper reviews the clinical and neurophysiologic arguments supporting the distinction between true myoclonus and various imitators, including chorea, ballism, tics, dystonia, stereotypy, tremor and restless limbs. To be differentiated from myoclonus, these movement disorders, despite their heterogeneity, are distinctive through the patterned profile of muscle activation, the longer duration of the muscle contraction, the conditions in which they occur, and their suppressibility at will. PMID- 17336778 TI - Drug-induced myoclonus: a French pharmacovigilance database study. AB - Various drugs have been reported to induce myoclonus. However, this adverse event is not well known because of the difficult diagnosis and the lack of pharmaco epidemiological or controlled studies. As far as we know, there are only case reports. In the literature, antiparkinsonian medications, antipsychotics, antidepressants, anesthetics, opiates and anti-infectious drugs have been reported in the occurrence of myoclonus. In a French pharmacovigilance database study, only 423 reports (0.2%) involved drug-induced myoclonus. The median age of patients was 55 years and 10% of these patients had a concomitant neurological disease. Only 16% of these reports had a strong imputability score (likely). The most frequently involved drugs were anti-infectious (15%), antidepressants (15%), anxiolytics (14%), and opiates agents (12%). Fifty-six percent of these reports were classified as serious adverse event. Concerning outcome, most patients (84%) recovered without sequels. PMID- 17336779 TI - Negative myoclonus. An overview of its clinical features, pathophysiological mechanisms, and management. AB - Negative myoclonus (NM) is an unspecific motor disorder that can characterize a variety of neurological conditions. From the clinical point of view, NM appears as a shock-like involuntary jerky movement caused by a sudden, brief interruption of muscle activity. Asterixis is a type of NM that occurs typically in toxic metabolic encephalopathies. NM of epileptic nature, or epileptic negative myoclonus (ENM), is defined as an interruption of tonic muscle activity, which is time-locked to an epileptic EEG abnormality, without evidence of an antecedent positive myoclonia in the agonist-antagonist muscles. ENM can be observed in idiopathic, cryptogenic, and symptomatic epileptic disorders. Pathophysiological hypotheses on the origin of NM involve subcortical as well as cortical mechanisms. Recent neuroimaging and neurophysiologic investigations, including intracerebral recordings and electrical stimulation procedures in epileptic patients, suggest the participation of premotor, primary motor, primary sensory, and supplementary motor areas in the genesis of NM. Polygraphic monitoring is essential for the diagnosis of NM, allowing the demonstration of brief interruptions of a tonic EMG activity, not preceded by a positive myoclonus in the agonist and antagonist muscles of the affected limb. Simultaneous EEG-EMG monitoring demonstrating the association of NM with an epileptic potential is consistent with the diagnosis of ENM. Evolution and prognosis of NM is mainly related to aetiology. In childhood idiopathic partial epilepsy, ENM can respond to some drugs (in particular, ethosuximide), whereas other medications (such as carbamazepine or phenytoin) have been reported to induce or worsen it. PMID- 17336780 TI - Cortical tremor (FCMTE: familial cortical myoclonic tremor with epilepsy). AB - For 15 years, 50 Japanese and European families with cortical myoclonic tremor and epilepsy were reported in the literature under various names. More recently, the acronym familial cortical myoclonic tremor with epilepsy (FCMTE) has been proposed for this new clinical entity based on both clinical and electrophysiological criteria: irregular postural myoclonic tremor of the distal limbs, familial history of epilepsy, autosomal dominant inheritance, and a rather benign outcome. The diagnosis is confirmed by electrophysiological features favoring cortical reflex myoclonus (enhanced C reflex at rest, giant somatosensory evoked potentials (SEPs), premyoclonus cortical spikes detected by the jerk-locked back-averaging method), and a good response to antiepileptic drugs. The genetic analysis of these families shows heterogeneity with a linkage to chromosome 8q24 for Japanese families, a linkage to chromosome 2p for Italian families, the exclusion of 8q24 locus for a Spanish family, and the exclusion of both loci for a Dutch family. The similarities of this syndrome with the group of myoclonic epilepsy suggest an abnormality of a gene encoding ion channels. PMID- 17336781 TI - Propriospinal myoclonus at sleep onset. AB - AIMS: To describe the clinical and polygraphic features of propriospinal myoclonus (PSM) at sleep onset. MATERIAL AND METHODS: PSM was first described in 1997 in patients with jerks occurring in the relaxation period preceding sleep. EMG showed jerks to arise in spinally innervated muscles, propagating thereafter to rostral and caudal muscles at a low speed, typical of propriospinal pathways. RESULTS: PSM arose when EEG alpha activity spread over the scalp and disappeared during either active wakefulness or actual sleep. In some patients EMG activity could sometimes remain localized to the abdominal muscles, propagating to other segments only in fully developed jerks. Neurological examination, brain and spinal MRI were usually normal and clonazepam afforded partial improvement. PSM has been recently observed also in restless legs syndrome, during relaxed wakefulness preceding falling asleep, coexisting with motor restlessness and sensory discomfort. PSM disappeared when spindles and K-complexes and typical Periodic Limb Movements appeared with EMG activity limited to leg muscles, without propriospinal propagation. CONCLUSIONS: Conceivably, PSM arises in axial muscles due to some spinal generator set into motion by facilitating influences characteristic of the wake-sleep transition and then undergoes multimeric propriospinal propagation. In the International Classification of Sleep Disorders (ICSD-2), PSM is listed in chapter VII, among the "Isolated symptoms, apparently normal variants and unresolved issues". PMID- 17336782 TI - Startle and its disorders. AB - Exaggerated startle is an uncommon feature of various neurological diseases, but is still lacking precise analysis in many of them. So far, electrophysiologic and cinematographic analyses allow discriminating two main subtypes. The prototype of primary exaggerated startle is hereditary hyperekplexia, a well-studied disorder of the inhibitory glycine receptor and thus of the neuronal Cl- channel. The involuntary jerking in hereditary hyperekplexia is considered a reticular reflex myoclonus. The prototype of primary normal startle with secondary abnormalities is startle epilepsy where a surprise stimulus typically provokes a normal startle, which in turn initiates a focal (most often frontal lobe) seizure with tonic posturing of the limbs. Clinical differential diagnosis between both subtypes may be difficult in individual cases, but there are abnormalities in clinical and neurophysiologic reflex testing, which need, however, broad validation. PMID- 17336783 TI - Anxiety of young female athletes with disordered eating behaviors. AB - The aim of this study was to investigate the prevalence rate of disordered eating behaviors in young female athletes and to compare the anxiety levels of the athletes with or without disordered eating behaviors. Female athletes (n=243) of 15 to 25 years old from the city, Edirne, in Turkey participated our study. Disordered eating behaviors and anxiety levels of participants were evaluated by the Eating Attitudes Test (EAT-40) and State-Trait Anxiety Inventory. Disordered eating behaviors was reported as 40 (16.7%) among all athletes. Both state and trait anxiety scores were higher in athletes with disordered eating behaviors than the athletes without disordered eating behaviors (p=0.01). The athletes who engage in leanness and non leanness sports were reported as having similar EAT-40 scores and anxiety scores. In conclusion, athletes with disordered eating behaviors have higher state and trait anxiety scores. PMID- 17336784 TI - Measurement of children's food intake with digital photography and the effects of second servings upon food intake. AB - This study tested the reliability and validity of measuring children's food intake with the digital photography method and the effects of second servings upon food intake. Food intake was measured in a school cafeteria for 5 days. Adiposity was assessed with body impedance analysis and body mass index, expressed as percentile rank. Mood and self-esteem were assessed with questionnaires. Estimates of food intake were highly reliable between two registered dietitians who independently estimated food intake. Boys ate more food than girls. A significant association between food intake and adiposity supported convergent validity. Non-significant correlations between food intake and depressed mood and self-esteem supported discriminant validity. When second servings were available, more food was selected and discarded, but mean food intake did not increase. Children who returned for second servings, however, ate more food when second servings were available, and a trend suggested that they also ate more food when second servings were not available. These findings support the reliability and validity of measuring children's food intake using digital photography and demonstrate its utility for studies of food intake and body weight. PMID- 17336785 TI - Impairment of cognitive performance in dietary restrained women when imagining eating is not affected by anticipated consumption. AB - Dietary restraint is associated with impairments on tasks requiring concurrent processing of food-related information and performance of a secondary cognitive task. The aim of the present study was to investigate whether manipulating information about post-task consumption of food enhances the cognitive impairments observed in restrained eaters when they are required to think about food at the same time as performing a simple reaction time task. On separate trials within the same session, restrained (n=29) and unrestrained eaters (n=29) were asked to imagine eating a slice of chocolate cake and drinking glass of water while performing a simple reaction time task. Half the participants were told that they would not be able to consume the cues following the task, while the other half were told that they would be required to eat the cake and drink the water. The reaction time performance of restrained eaters was slowed when imagining eating the cake, relative to imagining drinking the water in both the consumption and no consumption conditions. No effects of cue exposure on reaction time were found for unrestrained eaters. The results suggest that dietary restrained eaters are more reactive to food cues but that this effect is not modulated by information about post-task consumption of the food. PMID- 17336786 TI - Difficulties regulating emotions: Do binge eaters have fewer strategies to modulate and tolerate negative affect? AB - The current study evaluated whether difficulties regulating emotions explained unique variance in binge eating and examined which types of emotion regulation difficulties are most strongly associated with binge eating. The Eating Disorders Diagnostic Scale and the Difficulties in Emotion Regulation Scale were completed by 695 undergraduates. Hierarchical regression results indicated that difficulties regulating emotions accounted for a significant amount of the variance in binge eating over and above sex, food restriction, and over evaluation of weight and shape. Results also indicated that greater difficulty identifying and making sense of emotional states, and limited access to emotion regulation strategies were primarily responsible for the link between emotion regulation difficulties and binge eating. This supports a model of binge eating that includes emotional vulnerability and a deficit of skills to functionally modulate negative moods. PMID- 17336787 TI - Psychological factors associated with ratings of portion size: relevance to the risk profile for obesity. AB - The ability to assess accurately the relative size of food portions is highly variable in the population. This study was designed to identify salient individual differences that correlate with this variation since estimation errors are seen as a barrier to the control of food intake and a detriment to many obesity treatment strategies. Healthy weight and obese adult women were assessed on a self-report measure of food amount ratings. We predicted that a high sensitivity to reward, symptoms of binge eating, and a preference for fat foods would relate positive to scores on this rating scale, and that weight status might moderate these relationships. As expected, a preference for high-fat food was associated with the tendency to under-estimate portion sizes. A significant interaction between weight status and reward sensitivity indicated that high values on the latter were correlated with ratings reflecting under-estimation of food amounts--but only among obese individuals. This study identified important factors that may influence estimation biases in food amount ratings-information of direct relevance to research and treatment protocols that use food diaries and focus on efforts to normalize eating behaviours. PMID- 17336788 TI - Eating disorders and alcohol use: group differences in consumption rates and drinking motives. AB - Alcohol use and drinking motives were investigated among college women divided into four probable eating disorder groups: Bulimia Nervosa, purging subtype (BN n=16) Binge Eating Disorder (BED n=30) Eating Disorder, Not Otherwise Specified (EDNOS n=85) and Non-Eating Disordered Controls (NEDC n=252). Participants completed questionnaires that assessed eating behaviors and attitudes, motives for drinking alcohol, quantity and frequency of alcohol use, and binge drinking. The BED group reported greater weekend alcohol consumption and binge drinking than the EDNOS and NEDC groups. The BN and BED groups were significantly more likely to endorse Coping as a drinking motive than the EDNOS and NEDC groups. The NEDC group was more likely to endorse Mood Enhancement than the EDNOS group. These results offer one explanation for the relationship between eating and alcohol use disorders. Women with eating disorders may use alcohol to cope with negative affect, analogous to findings that women with eating disorders report binge eating to regulate negative affect [Mizes, J. S. (1985). Bulimia: A review of its symptomatology and treatment. Advances in Behavior Research and Therapy, 7, 91-142]. PMID- 17336789 TI - Taking action to lose weight: toward an understanding of individual differences. AB - The purpose of the present study was to understand differences in obese/overweight individuals who do and do not seek ongoing external assistance for weight loss. Help-seeking was examined as a dichotomous and as a continuous variable. Measures of body mass index, comorbid medical conditions, socioeconomic status, psychological distress, disordered eating behavior, body image, and obesity-related knowledge were administered to a community sample of 120 overweight women (age: 22-65 y, BMI: 25-63 kg/m(2)). Fewer predictors of help seeking were identified when measuring help-seeking as a dichotomy than when measuring it as a continuum. All predictors were from psychosocial domains, with obesity-related knowledge being the strongest, most consistent predictor. Help seeking for weight control in a community sample of overweight and obese individuals appears to be motivated by psychological aspects of obesity, rather than obesity's physical or medical burden. PMID- 17336790 TI - Reducing maladaptive weight management practices: developing a psychoeducational intervention program. AB - Previous research has addressed the issues of behavior change and eating disorder prevention among adolescents and young women. The current study was designed to evaluate: (a) whether an 8-week psychoeducational intervention can reduce maladaptive weight-management practices in women (University females, N=24) with sub-clinical levels of eating pathology; and (b) whether its implementation reduces the risk of developing more severe eating pathology across time. Participants were randomly assigned to an experimental (EX) group or a self monitoring control (SMC) group. Statistically significant changes on measures of eating pathology, including the Eating Attitudes Test-26 [Garner, D. M., Olmsted, M. P., Bohr, Y., & Garfinkel, P. (1982). The Eating Attitudes Test: psychometric features and clinical correlates. Psychological Medicine, 12, 871-878]; Forbidden Food Survey [Ruggerio, L., Williamson, D. A., Davis, C. J., Schlundt, D. G., & Carey, M. P. (1988). Forbidden Food Survey: Measure of bulimic's anticipated emotional reactions to specific foods. Addictive Behaviors, 13, 267-274]; and Bulimia Test-Revised [Thelen, M. H., Farmer, J., Wonderlich, S., & Smith, M. (1991). A revision of the bulimia test: The BULIT-R. Journal of Consulting and Clinical Psychology, 3(1), 119-124] were observed, as were changes in body image, as measured by the Body Shape Questionnaire [Cooper, P. J., Taylor, M. J., Cooper, Z., & Fairburn, C. G. (1987). The development and validation of the body shape questionnaire. International Journal of Eating Disorders, 6(4), 485-494]. Additional significant between-group differences in eating behavior, as measured by daily meal records, were also seen. Participants in the EX group evidenced improvements in scores which were significantly different from those observed in the SMC group. Unfortunately, attrition limited the utility of follow up data. PMID- 17336791 TI - Psychometric properties of the State and Trait Food Cravings Questionnaires among overweight and obese persons. AB - A crucial problem in studies involving food cravings is the lack of a psychometrically sound measure for use among overweight and obese populations. The degree to which the Food Cravings Questionnaires-Trait (FCQ-T) and State (FCQ S) evidenced acceptable psychometric properties among overweight and obese participants was assessed. In study 1, 109 participants completed the FCQ-T and FCQ-S. Item-total correlations, test-retest reliability, internal consistency, and factor structures were examined. Results indicate good internal consistency and partially support the factor structures. In study 2, the construct and predictive validity of the FCQ-S were examined. Twenty-eight women completed the FCQ-S 15 min after finishing a standardized breakfast and then twice more, 90 min apart. Subsequent ad libitum food intake was recorded. Results suggest that the FCQ-S is sensitive to state changes in food cravings, but that the magnitude of the changes was moderate. The FCQ-S was not a good predictor of subsequent food intake. The FCQ-T and FCQ-S may be useful in studies that examine triggers of and interventions for excessive food intake. PMID- 17336792 TI - Developmental considerations in measuring children's disordered eating attitudes and behaviors. AB - This study examined the discriminant ability of the Children's version of the Eating Attitudes Test (ChEAT) clinical cut-off in a low/low-middle socioeconomic status, non-clinical sample of primarily Hispanic and non-Hispanic white (Caucasian) girls aged 8 to 12. We investigated how age, age-standardized body mass index (z-BMI), body dissatisfaction, body esteem, self-esteem, and depressive symptoms contributed to disordered eating status in 152 girls. Girls scoring at/above the ChEAT clinical cut-off reported significantly greater body dissatisfaction and depressive symptoms and lower body esteem than did girls who scored below the cut-off. We then investigated whether age moderated the discriminant ability of the ChEAT threshold and found that the ChEAT was significantly more sensitive when our sample was limited to 10- to 12-year-olds. An abbreviated 6-item ChEAT scale, based on marker items distinguishing at-risk and non-clinical status, was subsequently developed. Findings indicate that this abbreviated ChEAT scale has improved sensitivity with older girls (10- to 12-year olds). However, sensitivity was unacceptable for younger girls (8- and 9-year olds) for both the ChEAT and abbreviated ChEAT scale, regardless of cut-off. PMID- 17336793 TI - Dietary restraint and disinhibition are associated with increased alcohol use behaviours and thoughts in young women social drinkers. AB - Previous studies have identified a positive relationship between dietary restraint and alcohol use. However, it is unclear whether heavier drinking is associated with higher dietary restraint per se, or restraint combined with a tendency towards disinhibition. The aim of the present study was to examine alcohol use behaviours in women classified using both restraint and disinhibition scores. Forty-four young female social drinkers gave self-reported measures of their drinking behaviour, including frequency and quantity of alcohol consumed and frequency of drunkenness and binge drinking. Attentional bias for alcohol related stimuli was also assessed using a dot probe detection task. Finally, the Temptation and Restraint Inventory was used to investigate whether preoccupation with drinking might underlie the relationship between dietary and drinking behaviours. Women classified as both highly restrained and disinhibited tended to report more episodes of drunkenness, showed an attentional bias for alcohol related words, and had greater cognitive preoccupation with drinking compared to other dietary groups. These data suggest that a tendency towards overeating (disinhibition) combined with attempts at restriction is associated with increased alcohol use behaviours, perhaps due to a greater preoccupation with alcohol. PMID- 17336794 TI - Peer pressure to "Fat talk": Does audience type influence how women portray their body image? AB - "Fat talk" describes women discussing their bodies disparangingly for impression management while interacting with one another. This study examined whether college females deliberately alter their self-reported body image according to characteristics of their prospective audience. This study was a mixed experimental design with four audience conditions (private, public, female audience, male audience) as the between-subjects factor and time across trials as the within-subjects factor using college females as participants (N=100). Pre versus posttest changes on the Body Esteem Scale (BES) and the Body Weight Figure Assessment (BWFA) served as the dependent variables. It was hypothesized that body image would decrease to indicate self-derogation (fat talk) in the public audience and female audience conditions, whereas body image would increase in the male audience condition. These hypotheses were not supported using repeated measures ANOVA. Strengths and weaknesses of the study are discussed. PMID- 17336795 TI - Effects of distress, alexithymia and impulsivity on eating. AB - OBJECTIVE: To improve our understanding of possible mechanisms underlying emotional overeating this study examined the effects of a distress manipulation on food intake in relation to alexithymia and impulsivity. METHOD: Participants were 86 females who were subjected to a distress manipulation (the anticipation of a public speaking task) prior to an ad lib taste task and filled out questionnaires on impulsivity and the alexithymia constructs difficulty identifying and describing feelings. RESULTS: Alexithymia significantly (p<.05) moderated the relationship between food consumption and distress. Instead of eating less in the distress condition, alexithymic females ate the same or even more, this showing a 'biological unnatural' and 'inapt' response. CONCLUSION: Findings suggest that for the 'natural' distress response (reduction of food intake) good ability to identify and describe feelings to others is required, and that the presence or absence of these abilities may predict which people respond to distress by undereating or by overeating. The results provide empirical support for Bruch's conceptualisation of poor interoceptive awareness as possible predictive factor for emotional overeating. PMID- 17336796 TI - Children's descriptions of the foods consumed during loss of control eating episodes. AB - Binge and loss of control (LOC) eating appear to be common among youth; however, little is known about the foods consumed during such eating episodes. Two-hundred forty-nine children, age 6-18 years, were interviewed to determine if they engaged in eating episodes with LOC over the past month. In the absence of reported LOC eating, overeating episodes or normal meals without LOC were recorded. Participants were asked to describe the type and quantity of foods eaten during an episode. Eighty-one children reported LOC eating episodes and 168 reported no such episodes (No LOC). Although total energy intake did not differ between LOC and No LOC episodes, LOC episodes consisted of a lower percentage of calories from protein (14.2+/-0.7 v. 18.0+/-0.7%, p<.001) and a higher percentage from carbohydrates (49.8+/-1.6 v. 45.2+/-1.1%, p<.05). Specifically, LOC episodes consisted of a higher percentage of calories from snacks (13.2+/-2.7 v. 7.4+/ 1.2%, p<.05) and desserts (18.1+/-3.1 v. 12.8+/-1.5%, p<.05). The quality of LOC episodes may help explain why LOC eating promotes excessive weight gain among children who report such episodes. PMID- 17336798 TI - Abstracts of the 7th Annual Cardiovascular Nursing Spring Meeting of the European Society of Cardiology Council on Cardiovascular Nursing and Allied Professions. March 23-24, 2007. Manchester, United Kingdom. PMID- 17336797 TI - Psychiatric and metabolic characteristics of childhood versus adult-onset obesity in patients seeking weight management. AB - The purpose of the study was to examine whether childhood-onset obesity differed from adult-onset obesity in lifetime prevalence of mood and eating disorders, and metabolic abnormalities, in currently obese adults seeking weight loss. A subgroup of childhood-onset obesity participants (N=44) was compared with a subgroup with adult-onset obesity (N=69) on a number of clinical and metabolic features. The results showed high lifetime prevalence rates of mood (78%) and eating (81%) disorders, and metabolic syndrome (45%), in the group as a whole. However, patients with childhood-onset obesity had a significantly higher lifetime prevalence of eating disorders in general, and of bulimia nervosa in particular, than patients with adult-onset obesity. Our results support findings of substantial comorbidity among obesity, mood and eating disorders, and metabolic syndrome in weight loss seeking populations. Early recognition and attention to eating and mood dysregulation, including, but not limited to binge eating disorder and bulimia nervosa, in some persons, might help reduce their lifetime risk for obesity. PMID- 17336799 TI - What can communication science tell us about promoting optimal dietary behavior? AB - Four of the 10 leading causes of death can be attributed to poor dietary behaviors. Nutrition professionals continue to struggle with the most effective ways to deliver nutrition messages that will result in changes in dietary behavior. On July 14-15, 2005, the National Cancer Institute and the Division of Nutrition Research Coordination, both of the National Institutes of Health, hosted a meeting to explore the state of the science concerning this issue. This paper provides an introduction to that meeting and the articles that resulted from it. PMID- 17336800 TI - Designing media messages about health and nutrition: what strategies are most effective? AB - This report focuses on how to design media messages about nutrition that will persuade people to adopt healthful behaviors. The Elaboration Likelihood Model (ELM) is used as a theoretical framework to explore different information processing modes that individuals employ in a variety of communication situations. Studies from the fields of communication and psychology are briefly reviewed, with a focus on the source and message strategies that are most likely to persuade different types of audiences to change their nutritional attitudes and behaviors. PMID- 17336801 TI - Social determinants and nutrition: reflections on the role of communication. AB - A healthy diet is considered a critical pathway in influencing chronic conditions such as hypertension, diabetes, cardiovascular disease, cancer, and obesity. The current information environment around diet and nutrition is complex and often confusing to the public. Though considerable evidence suggests that successful public health communication campaigns can promote health and prevent disease, studies also show that this success is subject to the influence of social determinants, such as social class, social networks, race and ethnicity, and neighborhood. Through a critical and selective review of literature on social epidemiology and public health communication, this paper explores how social determinants may mediate nutrition communication effects. PMID- 17336802 TI - Developing ratings for food products: lessons learned from media rating systems. AB - Children regularly consume low-nutrient, high-calorie food that is not consistent with a healthful diet, contributing to an increasing epidemic of overweight and obesity. Among the multiple causes of this problem is the food industry's emphasis on marketing calorie-dense food products to children. The Institute of Medicine (IOM) has recommended that industry adopt a uniform system of simplified food ratings to convey the nutritional qualities of food in a manner that is understandable and appealing to children and youth. This report analyzes the need for such a system in a food marketing environment that increasingly identifies healthful products for the consumer in inconsistent fashion. It considers evidence regarding current usage of food labeling and draws parallels with media rating systems in discussing the prospects for a uniform food rating system that would accomplish the IOM's objective. PMID- 17336803 TI - Health communication campaigns and their impact on behavior. AB - The objective is to review the evidence for the effectiveness of health communication campaigns to inform future nutrition campaigns. The review drew on existing meta-analyses and other literature. The average health campaign affects the intervention community by about 5 percentage points, and nutrition campaigns for fruit and vegetable consumption, fat intake, and breastfeeding, have been slightly more successful on average than for other health topics. The factors affecting success rates are discussed. The conclusion is that nutrition campaigns that pay attention to the specific behavioral goals of the intervention, target populations, communication activities and channels, message content and presentation, and techniques for feedback and evaluation should be able to change nutrition behaviors. PMID- 17336804 TI - News coverage of diet-related health disparities experienced by black Americans: a steady diet of misinformation. AB - Compared to their white counterparts, black Americans experience greater morbidity and mortality across a range of diet-related diseases and conditions, including heart disease, type II diabetes, cancer, stroke, and obesity. Many factors influence dietary behaviors among blacks, including those associated with socioeconomics, culture, racism, psychology, and health care quality and access. However, when reporting about the health status and dietary behavior of black Americans, the mainstream print media pursues a largely one-dimensional focus on behavioral and cultural factors. This approach tends to disregard or minimize other factors that influence health behaviors. Health scientists and journalists must be careful to include discussion of the other factors if they want to become a part of the solution to minimize diet-related disparities. PMID- 17336805 TI - Moving nutrition upstream: the case for reframing obesity. AB - Currently, nutrition is described primarily as a matter of individual responsibility, which results in a focus on limited strategies that are unlikely to be successful. Public health advocates need to change the terms of debate or "reframe" the issue so that the context around individuals-the social, economic, and political context--comes into view. This paper uses obesity as an example of the need for reframing in nutrition. The authors also offer some suggestions on reframing based on lessons learned from other public health issues. PMID- 17336806 TI - Communication and diet: an overview of experience and principles. AB - As nutrition officials face the need to address widespread chronic obesity and its associated diseases, many have turned to media campaigns as a strategy for reaching large audiences. In the past, such efforts have had mixed results. Examples of successful and unsuccessful major public health campaigns are presented, including a small number related to diet. One implication of the analysis of those cases is the importance of obtaining high levels of exposure to messages. Several strategies for maximizing exposure are elaborated, including the use of paid advertising, relying on donated time, and earning coverage through media advocacy. PMID- 17336807 TI - Controlling holiday weight gain: lessons from the Lean Plate Club. PMID- 17336808 TI - Lessons from VERB: a case for branding in nutrition education. PMID- 17336809 TI - The 5-4-3-2-1 go! Intervention: social marketing strategies for nutrition. PMID- 17336810 TI - The recent evolution of news organizations toward web-based healthful eating and weight management tools. PMID- 17336811 TI - Communicating healthy eating: lessons learned and future directions. AB - Achieving and maintaining wide-scale positive dietary change is a complex and formidable endeavor, given the current food environment. Moreover, for positive change to occur, nutrition messages should be communicated in a scientifically precise, yet practical and motivating manner. This challenge was the impetus for the organization of a 2-day workshop hosted by the National Cancer Institute (NCI) and the Division of Nutrition Research Coordination (DNRC), both of the National Institutes of Health (NIH). The conference included communication, nutrition, and behavioral scientists, market researchers, media advocates, journalists, and public policy experts. Discussions regarding communication efforts and the best methods to craft, deliver, and evaluate the impact of nutrition messages illustrated both the challenges and the opportunities we face. During the discussions, important recommendations for nutrition communicators and interventionists emerged, based on existing knowledge from the communications field, lessons learned thus far, and noted gaps in our knowledge. PMID- 17336812 TI - Influence of intimate partner violence during pregnancy and early postpartum depressive symptoms on breastfeeding among chinese women in Hong Kong. AB - Numerous studies show that breastfeeding is beneficial to both mothers and babies. This study explores two understudied correlates that may influence breastfeeding initiation: intimate partner violence during pregnancy and early postnatal depressive symptoms. A cross-sectional comparative study design investigated the correlates of feeding modes of 1200 Chinese mother and infant pairs in a university-affiliated regional hospital in Hong Kong. The prevalence rates of breastfeeding and mixed feeding were 42.25% and 26.25%, respectively. Women who had no experience of intimate partner violence during pregnancy were significantly more likely to initiate breastfeeding (adjusted odds ratio = 1.84; 95% confidence interval, 1.16-2.91) after adjustment for demographic, socioeconomic, and obstetric variables. Early postnatal depressive symptoms were not significantly associated with feeding modes in a multinomial logistic regression model. Midwives are in a key position to identify and intervene to encourage more successful breastfeeding practice. PMID- 17336813 TI - Midwifery research: rights and responsibilities. PMID- 17336814 TI - Developing midwifery knowledge: setting a research agenda. PMID- 17336815 TI - Finding midwifery in administrative data systems. AB - Nurse-midwifery has accomplished remarkable clinical, policy, and political achievements using specially-collected data. Today, midwifery practice data can be found in existing administrative data systems: birth registration, hospital data depositories, and claims files. Issues in finding midwifery as practice and profession in these data systems are discussed. Improving the integrity of data that reveal midwives as caregivers should be a priority. PMID- 17336816 TI - Survey of Connecticut Nurse-Midwives. AB - Descriptive data on nurse-midwifery income, workload, job definitions, employment benefits, and clinical practices are limited. Information about nurse-midwifery practice today is important for the growth of the profession and for future policy initiatives. A survey of nurse-midwives in Connecticut was conducted in 2005. This article reports state-specific data about income, workload, job definitions, employment benefits, and clinical issues, such as vaginal birth after cesarean. Full-time midwives in Connecticut worked an average of 77 hours per week, had a mean salary of 79,554 dollars, and 87% had on-call responsibilities. A "typical" Connecticut midwife had an "average" full-time work week consisting of two 24-hour call days and three 7-hour office days, seeing 19 to 24 patients per office day. Most held Master of Science in Nursing degrees, worked in physician-owned practices, and attended births in hospitals or medical centers. Health insurance, paid sick time, and retirement plans were offered to most respondents. Almost all respondents provide gynecologic, antepartum, and postpartum care, but few offer newborn care. There is significant variation in restrictions on midwives offering vaginal birth after cesarean and on length of scheduled appointments. Data on expanded practices, such as first-assisting caesarean sections and endometrial biopsies, are reported for the first time. PMID- 17336817 TI - Randomized controlled trial of very early mother-infant skin-to-skin contact and breastfeeding status. AB - This study was done to evaluate effects of maternal-infant skin-to-skin contact during the first 2 hours postbirth compared to standard care (holding the infant swaddled in blankets) on breastfeeding outcomes through 1 month follow-up. Healthy primiparous mother-infant dyads were randomly assigned by computerized minimization to skin-to-skin contact (n = 10) or standard care (n = 10). The Infant Breastfeeding Assessment Tool was used to measure success of first breastfeeding and time to effective breastfeeding (time of the first of three consecutive scores of 10-12). Intervention dyads experienced a mean of 1.66 hours of skin-to-skin contact. These infants, compared to swaddled infants, had higher mean sucking competency during the first breastfeeding (8.7 +/- 2.1 vs 6.3 +/- 2.6; P < .02) and achieved effective breastfeeding sooner (935 +/- 721 minutes vs 1737 +/- 1001; P < .04). No significant differences were found in number of breastfeeding problems encountered during follow-up (30.9 +/- 5.51 vs 32.7 +/- 5.84; P < .25) or in breastfeeding exclusivity (1.50 +/- 1.1 vs 2.10 +/- 2.2; P < .45). Sucking competency was also related to maternal nipple protractility (r = .48; P < .03). Very early skin-to-skin contact enhanced breastfeeding success during the early postpartum period. No significant differences were found at 1 month. PMID- 17336818 TI - Women's perspectives on maternity services in Sweden: processes, problems, and solutions. AB - Most measures of health care quality focus on medical outcomes rather than patients' assessments of quality. Drawing on data from a national survey of Swedish women, this study describes women's opinions about what is important to them during pregnancy and birth. This qualitative study is based on responses of 827 pregnant women to an open question completed in the second trimester. In total, 2061 separate statements were analyzed. Using content analysis, these statements were clustered into 4 themes: desirable characteristics of midwife, prenatal care during pregnancy, care during labor and birth, and care after birth. Within those themes, 13 categories were found. Findings suggest areas for improvement in maternity services including: the timing and length of prenatal visits, making parent education classes available to all women, prelabor visits to the maternity ward, continuous information about the progress of labor, flexibility in time of discharge, and postpartum support for families. Women also stated that characteristics of the midwife, such as being supportive, friendly, attentive, respectful, and nonjudgemental, were important. A patient-centered and individualized approach, with women and their partners as the subjects rather than the objects of care, would increase satisfaction and the overall quality of maternity services in Sweden. PMID- 17336819 TI - Why do supportive birth attendants become directive of maternal bearing-down efforts in second-stage labor? AB - A supportive approach to care for women during the second stage of labor that primarily relies on the laboring woman's involuntary expulsive urges has been advocated. We aimed to learn about the clinical circumstances surrounding the caregiver shift from being primarily supportive to directing women regarding their bearing-down efforts. This research analyzed the communications of 10 birth attendants and women during the expulsive phase of labor using videotapes recorded from two studies carried out between 1986 and the present. The occasions when a birth attendant shifted verbalizations were identified, and categories of the rationales that may have influenced the modification in caregiver behavior were developed. Birth attendants most frequently provided directions to help the woman push effectively, that is, to focus the woman's bearing-down efforts during maternal distress, fatigue, fear, and pain to expedite the labor process (38% of the occasions of caregiver change in verbalizations). The next most frequent clinical situations when caregivers offered directions about "pushing" were diminished urge to bear-down with epidural analgesia (10%), routine arbitrary practices (9% caregiver and 6% by supportive companion), and fetal distress (<1%). A category of "supportive direction" (20%) was identified. This care strategy has not been previously reported. It combined direction with support in a way that was supportive rather than overriding the woman's involuntary efforts. PMID- 17336820 TI - Midwives in the UK: an exploratory study of providing newborn feeding support for postpartum mothers in the hospital. AB - Our objective was to explore English midwives' views and experiences of supporting mothers with feeding their newborn baby. Grounded theory methodology was used. Data were collected using in-depth interviews from 30 midwives in the North of England. Data were analyzed using constant comparison techniques. Midwives were theoretically sampled for interview from a pool of volunteers recruited from a poster promoting the study in the clinical areas. Overall, hospital midwives felt that they did not have enough time to support mothers with feeding their neonate. To cope with these time constraints, midwives developed practices of rationing the time that they spent with mothers, and the rationing of resources available to mothers, to help them process mothers through the hospital services. These practices have important implications for the success of breastfeeding in hospitals as the practices by providers who are assigned to help breastfeeding initiation described here may inhibit the breastfeeding process. PMID- 17336821 TI - Reasons for unprotected intercourse in adult women: a qualitative study. AB - Despite the focus on adolescents, most unintended pregnancies occur in adults. The objective of this study was to identify reasons why adult women have unprotected intercourse when they do not desire pregnancy. We held 4 focus groups to explore reasons for unprotected intercourse. Participants were adult women aged 18 to 39 who were unmarried, fertile, not currently pregnant, not desiring pregnancy, and who had recently had intercourse without using effective contraception. Sessions were audiotaped and transcripts were analyzed thematically. Women gave 146 reasons for unprotected intercourse. Four major categories emerged: method-related, user-related, partner-related, and cost/access-related reasons. The reasons for unprotected intercourse were numerous, but could be organized into a logical framework. The results suggest that multidimensional interventions may be needed to effectively reduce the rate of unintended pregnancy. PMID- 17336822 TI - An update on vicarious liability for certified nurse-midwives/certified midwives. AB - The unique placement of midwives in the health care industry prompts renewed consideration of vicarious liability. Generally, vicarious liability is the liability of an employer for an employee's actions. A review of recent case law over the past decade shows limited case activity and indicates that the certified nurse-midwife/certified midwife (CNM/CM) roles do not create vicarious liability risks different from any other employee/agent. The lack of case law signals a lack of dispute over vicarious liability, not a lack of liability. Absent unique statutory provisions, which may be in effect in a minority of states, an employer of a CNM/CM is as liable for the midwife's negligence committed in the scope of their employment as employers are generally liable for an employee's negligence. When there is no employment/agency relationship, vicarious liability does not apply. A collaborative practice agreement is a good example of a nonemployment arrangement. Proper contractual documentation of relationships and comprehensive professional liability coverage are necessary to manage this form of liability. PMID- 17336823 TI - Female genital mutilation: cultural awareness and clinical considerations. AB - Clinicians in the United States are increasingly encountering girls and women who have undergone female genital mutilation. To foster a more trusting relationship with such patients, health care providers must have an accurate understanding of the cultural background surrounding this practice, a working knowledge of the different types of female genital mutilation procedures that may be encountered, and an awareness of both the acute and long-term complications. Some of these complications are potentially fatal, and the correct clinical diagnosis can be lifesaving. PMID- 17336827 TI - Midwifery in action. PMID- 17336824 TI - Management options for women with midtrimester fetal loss: a case report. PMID- 17336828 TI - Autoimmune lymphoproliferative syndrome (ALPS) in a patient with a new germline Fas gene mutation. AB - Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder characterized by chronic lymphoproliferation, autoimmune manifestations and expansion of TCRalphabeta+CD4-CD8- lymphocytes. The main pathogenic factor is a defective Fas-mediated apoptosis generally caused by mutations in the Fas gene. This report describes a new heterozygous Fas gene mutation in a boy with clinical and immunological features of ALPS. In vitro, T-cell blasts from the patient are completely resistant to the effects on the anti-Fas cytotoxic mAb CH-11, they also have a higher proliferation rate than T cells from healthy donors, while PHA induced AICD is normal. The location of the mutation (I246S) found in the intracytoplasmic death domain, and the conservation of that residue in four different species from human suggest that I246 is an essential amino acid for Fas function. The patient has inherited the mutation from his father who also shows defective Fas-mediated apoptosis but the clinical and immunological manifestations are much less severe. These results provide evidence that the penetrance of genetic defects in Fas is variable and that other factors may influence the phenotype of the disease. PMID- 17336829 TI - On the role of CD26 in CD4 memory T cells. AB - We studied an in vivo mouse model to evaluate the relationships between CD26--a glycoprotein with dipeptidyl peptidase IV (DPP-IV) activity implicated in the regulation of immune functions--and T cells expressing the effector/memory phenotype CD45RB. We report that CD26 does not define a differentiation stage of CD4 T cells because the density and frequency of CD26 on CD4 T cells from the spleen, inguinal and mesenteric lymph node was similar within the CD45RB+ (naive) and CD45RB- (antigen primed) subsets. This observation was confirmed using CD4 T cells from a T-cell receptor transgenic (tg) model. CD4 tg T cells specific for ovalbumin (OVA) were adoptively transferred and challenged in vivo with antigen. CD26 expression was the same on naive and antigen-stimulated CD4 T cells. Depleting CD4 T cells with an anti-CD4 antibody preferentially depleted the CD45RB+ subset. In CD4 depleted animals CD26 expression was not altered on the CD45RB- subset but the density of CD26 was marginally increased on the remaining CD45RB+ CD4 T cells. The results suggest that, unlike the human, CD26 in the mouse was not directly linked with T cell activation. PMID- 17336830 TI - Reactive oxygen species (ROS), but not nitric oxide (NO), contribute to strain differences in the susceptibility to experimental arthritis in rats. AB - There is extensive evidence for the critical role of reactive oxygen species (ROS) and nitric oxide (NO) produced by phagocytes in development of inflammatory processes and pathogenesis of numerous diseases, including rheumatoid arthritis (RA). Apart from their function as mediators of inflammation and tissue damage, recent research supports their role as signaling and regulatory molecules. In the present study we have investigated the production of ROS and NO over the course of adjuvant arthritis (AA) and oil-induced arthritis (OIA), by resident peritoneal macrophages of two rat strains: Dark Agouti (DA), susceptible, and Albino Oxford (AO), resistant to induction of AA and OIA. We have compared levels of ROS and NO produced by susceptible vs. resistant rat strain, and investigated their relevancy for arthritis development and severity. In addition, we have stimulated macrophages in vitro with Mycobacterium bovis BCG, and two heat shock proteins (HSP): endogenous HSP47 and mycobacterial HSP71 (mHSP71). Our results suggest a possible contribution of increased ROS production to arthritis resistance of AO rats. The ROS production in AO rats is potentiated by endogenous HSP47, but not with mycobacterial cell and mHSP71, suggesting HSP47 participates in AA control. We have found no fundamental relationship between the magnitude of NO production and AA and OIA susceptibility and severity, suggesting that NO has no effector role in AA and OIA. Our results advocate a regulatory type action of NO molecule might be more significant in arthritis development. PMID- 17336831 TI - Milk fermented by Lactobacillus helveticus R389 and its non-bacterial fraction confer enhanced protection against Salmonella enteritidis serovar Typhimurium infection in mice. AB - Bacterial infections in the gastrointestinal tract represent a major global health problem, even in the presence of normally effective mucosal immune mechanisms. Milk fermented by Lactobacillus helveticus R389 (FM) or its non bacterial fraction obtained by milk fermentation at controlled pH 6 (NBF) are able to activate the small intestine mucosal immune response according to previous studies. In this work we aimed at comparing their protection capacity against an infection by Salmonella enteritidis serovar Typhimurium and at studying the mechanisms involved. In a completely randomized design, BALB/c mice received FM or NBF for 2, 5 or 7 consecutive days, followed by a single oral challenge with S. Typhimurium (10(7) cells/mouse). The increase in the number of IgA+ cells in the lamina propria of the small intestine, after the feeding periods, was accompanied by an increase in the luminal content of total S-IgA. However, no antibodies were produced against the NBF. In mice given the FM or the NBF for 7 consecutive days, lower levels of liver colonization on day 7 post challenge with S. Typhimurium, higher luminal contents of specific anti Salmonella S-IgA, higher percentages of survival to infection and lower numbers of MIP-1alpha+ cells in the lamina propria were observed. In this work we observed that in both the FM or the NBF there are active principles that confer enhanced protection against S. Typhimurium infection. However, the mechanisms underlying mucosal immunomodulation and protection are different. In those mechanisms, the mucosal immune response would seem to be more involved than the competitive or exclusion mechanisms between L. helveticus R389 and S. enteritidis serovar Typhimurium. PMID- 17336832 TI - Generation of antibodies specific to D-mannitol, a unique haptenic allergen, using reductively aminated D-mannose-bovine serum albumin conjugate as the immunogen. AB - D-mannitol is commonly used as a food additive and excipient due to its sweetness, non-toxicity, and low calorific value. However, several cases of hypersensitivity reactions to mannitol have been reported. Owing to its inert nature, mannitol cannot produce an immunological response. In order to explain the mechanism of immunogenicity of mannitol, a method to obtain mannitol epitopes on a carrier protein, which serves as an immunogen to generate antibodies against mannitol, is described. In the present investigation, D-mannitol-specific polyclonal antibodies were generated by immunizing rabbits with reductively aminated mannose-bovine serum albumin (BSA) (33 haptens/molecule) as the hapten carrier conjugate. Anti-mannitol IgG antibodies were purified from the immune serum by hapten-affinity chromatography on a D-mannitol-keyhole limpet hemocyanin (KLH)-Sepharose CL-6B affinity matrix. The yield of mannitol-specific antibodies was approximately 40 microg per mL of rabbit antiserum. The specificity of the purified antibodies towards D-mannitol was demonstrated by hapten-inhibition in enzyme-linked immunosorbent assay (ELISA). The affinity-purified antibodies were found to be very specific to D-mannitol showing less than 5% cross-reactivity with other sugars and sugar alcohols, with the exception of its epimer, sorbitol, which showed 8.8% cross-reactivity. Importantly, the antibodies showed <1% cross reactivity with L-mannitol epitope, thus exhibiting configurational specificity. The inhibition studies provided evidence for the haptenic nature of mannitol and confirmed that the mannitoyl group is a single epitope. The reaction scheme utilized here for the generation of mannitol epitopes provides the basis for the immunogenicity of mannitol. PMID- 17336833 TI - Use of monoclonal antibodies to assess expression of anaphylatoxin receptors in tubular epithelial cells of human, murine and rat kidneys. AB - To assess published evidence of anaphylatoxin receptor expression in renal tubular epithelial cells, monoclonal antibodies (mAbs) against human, mouse and rat receptors for C5a and C3a (C5aR, C3aR) were raised using receptor-expressing transfectants as immunogens. Applying these reagents in immunohistochemistry, we observed that mAbs with reactivities against three distinct epitopes of human C5aR N-terminus recognized tissue macrophages but not at all renal tubular epithelial cells. These findings were surprising, as strong tubular staining had been previously demonstrated by mAbs raised against a synthetic N-terminal C5aR peptide. To extend our study to mammalian kidneys, renal specimens from normal rats as well as LPS-treated Balb/c and MRL/lpr mice, which suffered from lupus type nephritis, were examined. Similar to humans, mAbs against murine or rat C5aR strongly recognized infiltrating leukocytes in situ whereas tubular epithelial cells remained negative. As a mAb has been previously used to document C3aR expression in renal tubular epithelial cells, kidney specimens were examined using newly established mAbs against different epitopes of human, murine and rat C3aR. In contrast to published evidence, C3aR was detectable exclusively in interstitial leukocytes but not in epithelial tubular cells of normal and diseased tissues. Taken together, our findings question a direct involvement of tubular epithelial cells in anaphylatoxin-mediated renal inflammation. Furthermore, as we demonstrate in the case of anaphylatoxin receptors, cross reactivities of mAbs may constitute as yet underestimated pitfalls in immunohistochemical antigen detection. PMID- 17336834 TI - Rice (Oryza sativa) allergy in rhinitis and asthma patients: a clinico immunological study. AB - Sensitization to foods varies in different countries reflecting a possible interaction of genetic factors, cultural and dietary habits. Rice is a major food consumed world wide and needs evaluation for IgE mediated reactions. The present study was carried out to identify rice allergy in patients of rhinitis and asthma and identify the allergenic proteins in raw and cooked rice. Of 1200 patients screened using standard questionnaire, 165 presented with history of rice allergy. Of these, 20 (12.1%) patients demonstrated marked positive skin prick test (SPT) and 13 showed significantly raised specific IgE to rice compared to normal controls. Double blind placebo controlled food challenge (DBPCFC) confirmed rice allergy in 6/10 patients. Immunoblot with hypersensitive individual patients' sera showed 14-16, 33, 56 and 60 kDa proteins as major IgE binding components in rice. Boiled rice retained four IgE reactive proteins of 16, 23, 33 and 53 kDa. In summary, IgE-mediated rice allergy affects 0.8% [(0.42 1.58) at 95% CI] of asthma and rhinitis cases. The subjects with severe SPT reactions (4 mm or above) and specific IgE, 6.9 ng/ml to rice demonstrated positive blinded food challenge with clinical symptoms. PMID- 17336835 TI - Biomechanical evaluation of the ligamentous stabilizers of the scaphoid and lunate: part III. AB - PURPOSE: This study continued our previous investigations of the ligaments stabilizing the scaphoid and lunate in which we examined the scapholunate interosseous ligament, the radioscaphocapitate, and the scaphotrapezial ligament. In this current study, we examined the effects of sectioning the dorsal radiocarpal ligament, dorsal intercarpal ligament, scapholunate interosseous ligament, radioscaphocapitate, and scaphotrapezial ligaments. In the current study, the scapholunate interosseous ligament, radioscaphocapitate, and scaphotrapezial ligaments were sectioned in a different order than performed previously. METHODS: Three sets of 8 cadaver wrists were tested in a wrist joint motion simulator. In each set of wrists, only 3 of the 5 ligaments were cut in specific sequences. Each wrist was moved in continuous cycles of flexion extension and radial-ulnar deviation. Kinematic data for the scaphoid and lunate were recorded for each wrist in the intact state, after the 3 ligaments were sectioned in various sequences and after the wrist was moved through 1,000 cycles of motion. RESULTS: Dividing the dorsal intercarpal or scaphotrapezial ligaments did not alter the motion of the scaphoid or lunate. Dividing the dorsal radiocarpal ligament alone caused a slight statistical increase in lunate radial deviation. Dividing the scapholunate interosseous ligament after first dividing the dorsal intercarpal, dorsal radiocarpal, or scaphotrapezial ligaments caused large increases in scaphoid flexion and lunate extension. CONCLUSIONS: Based on these findings, we concluded that the scapholunate interosseous ligament is the primary stabilizer and that the other ligaments are secondary stabilizers of the scapholunate articulation. Dividing the dorsal radiocarpal, dorsal intercarpal, or scaphotrapezial ligaments after cutting the scapholunate interosseous ligament produces further changes in scapholunate instability or results in changes in the kinematics for a larger portion of the wrist motion cycle. PMID- 17336836 TI - Effects of the deep anterior oblique and dorsoradial ligaments on trapeziometacarpal joint stability. AB - PURPOSE: Osteoarthritis of the trapeziometacarpal (TMC) joint of the thumb affects as many as 25% of postmenopausal women and 5% of middle-aged men. This study investigated the relative contribution of the dorsoradial ligament (DRL) and the deep anterior oblique ligament (dAOL) to the stability of the TMC joint. This knowledge will improve our understanding of the pathomechanics of osteoarthritis at the base of the thumb and may help to design novel reconstructive surgical procedures. METHODS: Seventeen intact cadaver hands were dissected to reveal the DRL and dAOL. Either the DRL or dAOL was transected randomly, physiologic muscle loads were applied to simulate lateral key pinch or thumb opposition, or a 3-dimensional magnetic tracking system was used to record the position of the thumb metacarpal relative to the trapezium. The differences in the 3-dimensional positions between the control and transected states were determined. RESULTS: In lateral pinch, transection of the DRL resulted in a mean increased 3-dimensional translation of 1.3 mm, whereas transection of the dAOL resulted in a mean increased 3-dimensional translation of 0.6 mm. Statistically significant 2-dimensional findings in lateral pinch after transecting the DRL or dAOL included an increased palmar subluxation of 0.3 mm and 0.2 mm, an increased radial (1.0 mm) and ulnar (0.3 mm) translation, and an increased pronation of 4.1 degrees and 2.4 degrees, respectively. In thumb opposition, transection of the DRL resulted in a mean increased 3-dimensional translation of 1.0 mm, whereas transection of the dAOL resulted in a mean increased 3-dimensional translation of 0.5 mm. CONCLUSIONS: In most degrees of freedom of metacarpal movement relative to the trapezium, the DRL is relatively more important than the dAOL in providing stability to the TMC joint. PMID- 17336837 TI - Perilunate fracture-dislocations of the wrist: comparison of temporary screw versus K-wire fixation. AB - PURPOSE: Temporary intercarpal screw fixation has been suggested as an alternative to temporary K-wire fixation in the treatment of perilunate wrist dislocations. We compared the 2 treatment methods in 2 retrospective cohorts with a null hypothesis that there would be no difference in final wrist motion. METHODS: Eighteen patients with surgically treated perilunate wrist dislocations (9 treated with intercarpal screws, 9 with intercarpal K-wires) were evaluated an average of 44 months after injury. The intercarpal screws were removed an average of 5 months and the K-wires an average of 3 months after the initial procedure. Complications included 3 pin track infections (1 with wrist sepsis), 2 scaphoid nonunions (screw fixation), and 2 patients with loss of reduction (K-wire fixation) treated with repeat surgery. RESULTS: Four patients (2 in each cohort) had wrist arthrodesis with poor results. Among the 14 remaining patients the final flexion arc was 97 degrees for patients treated with screw fixation compared with 73 degrees for patients treated with K-wires. The mean grip strength was 74% (screw fixation) and 67% (K-wire) that of the uninjured arm. According to the Mayo Modified Wrist Score, the functional result was excellent in 1 patient (screw), good in 2 patients (1 each group), fair in 6 patients (3 in each group), and poor in 9 patients (4 screws, 5 K-wire). Seven patients (2 screws, 5 K-wires) had grade 2 or 3 midcarpal arthritis according to the criteria of Knirk and Jupiter, but none had more than mild radiocarpal arthritis. CONCLUSIONS: The results of treatment with temporary screws are comparable to the results of treatment with temporary K-wires. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 17336838 TI - Internal fixation of acute, nondisplaced scaphoid waist fractures via a limited dorsal approach: an assessment of radiographic and functional outcomes. AB - PURPOSE: To evaluate the clinical and radiographic outcomes of a consecutive series of patients who had internal fixation of an acute, nondisplaced scaphoid waist fracture via a limited dorsal approach. METHODS: Twenty consecutive patients had surgical fixation of a nondisplaced scaphoid waist (Herbert B2) fracture via a limited dorsal approach. Eighteen patients were available for follow-up evaluation at a mean duration of 98 weeks after surgery (range, 12-272 wk). Fifteen males and 3 females with a mean age of 25 years (range, 16-62 y) were examined. Wrist range of motion; grip strength; visual analog and numeric pain scores; and a Disabilities of the Arm, Shoulder, and Hand (DASH) outcomes questionnaire were assessed. Postoperative radiographs were reviewed in a blinded fashion to assess the fracture union and screw position. RESULTS: Seventeen of 18 fractures healed at a mean duration of 8 weeks. No case of proximal pole avascular necrosis occurred. All patients were satisfied and returned to their pre-injury level of employment. Five of 6 collegiate or professional athletes returned to play without limitations. The mean subjective and visual analog pain scores were 0.3 and 0.4 (maximum of 10 for each scale). The mean DASH score was 6.12 (out of 100), which is consistent with an excellent functional outcome. Central axis screw position was achieved on anteroposterior and lateral radiographs in 17 of 18 patients. CONCLUSIONS: Fixation of an acute, nondisplaced scaphoid waist fracture via a limited dorsal approach is safe and effective. The limited dorsal approach allows for accurate insertion of the screw in the central scaphoid, which is biomechanically advantageous for fracture union and early restoration of function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 17336839 TI - Pisiform impingement after total wrist arthroplasty. AB - We present a 64-year-old woman with rheumatoid arthritis who developed increasing pain 3 years after a total wrist arthroplasty. The pain was localized over the ulnar side of the wrist secondary to erosion of the pisiform. Pisiform excision resulted in a resolution of the symptoms. When placing a carpal component, which includes a base plate as part of its design, care should be taken to avoid any overhang of the implant edge into the pisotriquetral joint. PMID- 17336840 TI - Immunohistochemical evidence of nerve growth factor in Dupuytren's diseased palmar fascia. AB - PURPOSE: Histologically, the pathognomic feature of Dupuytren's contracture (DC) is the myofibroblast. Its occurrence in this disease has been associated with local production of transforming growth factor (TGF)-B. However, nerve growth factor (NGF) is a recognized growth factor involved in wound healing and has been shown to induce the myofibroblast phenotype in cultured fibroblasts. We hypothesized that NGF would be abundant in this disease entity. METHODS: Immunohistochemistry was used to examine for the presence of NGF in 25 surgical specimens from patients with DC and in surgical specimens from 5 other, unrelated procedures. Patient demographics showed that nearly all patients were men, with a mean age of 61 years (range 36-77). Serial sections were probed with antibodies, stained, and then digitally photomicrographed. Disease staging was also performed. Image analysis was then used to measure the percentage of area stained. In addition, representative sections were probed for TrkA, the high affinity receptor for NGF, and alpha-smooth muscle actin, a cytoskeletal marker of the myofibroblast phenotype. These alternate steps were used to infer functional dependence and the association of NGF with myofibroblast populations. RESULTS: Histologically, all patients had either stage II or III disease. Biopsy results showed an abundance of NGF--over double that of controls. The highest levels of NGF occurred in hypercellular stage II disease. In addition, we confirmed that NGF is linked to the expression of both TrkA receptors and alpha smooth muscle actin. CONCLUSIONS: Tissue levels of NGF are elevated in Dupuytren's disease. This tissue is competent to respond to NGF and manifests an abundance of myofibroblasts in areas of NGF expression. Nerve growth factor is most apparent in the proliferative (hyperplastic) stage of the disease. These data infer that NGF is linked to the pathologic process. PMID- 17336841 TI - A complete expression profile of matrix-degrading metalloproteinases in Dupuytren's disease. AB - PURPOSE: Dupuytren's disease (DD) is a common fibrotic condition of the palmar fascia, leading to deposition of collagen-rich cords and finger contractions. The metzincin superfamily contains key enzymes in the turnover of collagen and other extracellular matrix macromolecules. A number of broad-spectrum matrix metalloproteinase inhibitors, used in cancer clinical trials, caused side effects of DD-like contractures. We tested the hypothesis that changes in the expression of specific metalloproteinases underlie or contribute to the fibrosis and contracture seen in DD. METHODS: We collected tissue from patients with DD and used normal palmar fascia as a control. We profiled the expression of the entire matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMP), and a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) gene families in these tissues using real-time reverse-transcription polymerase chain reaction. RESULTS: A number of metalloproteinases and inhibitors are regulated in DD. The expression of 3 key collagenases, MMP1, MMP13, and MMP14 is increased significantly in the DD nodule, as is the expression of the collagen biosynthetic enzyme ADAMTS14. The expression of MMP7, an enzyme with broad substrate specificity, is increased in the DD nodule and remains equally expressed in the DD cord. TIMP1 expression is increased significantly in DD nodule compared with normal palmar fascia. CONCLUSIONS: This study measured the expression of all MMP, ADAMTS, and TIMP genes in DD. Contraction and fibrosis may result from: (1) increased collagen biosynthesis mediated by increased ADAMTS-14; (2) an increased level of TIMP-1 blocking MMP-1- and MMP-13-mediated collagenolysis; and (3) contraction enabled by MMP-14-mediated pericellular collagenolysis (and potentially MMP-7), which may escape inhibition by TIMP-1. The complete expression profile will provide a knowledge-based approach to novel therapeutics targeting these genes. PMID- 17336843 TI - Ectopic Dupuytren's disease: a commentary. PMID- 17336842 TI - Dupuytren's disease involving the wrist. AB - There is a well-established association with ectopic fibrosis in Dupuytren's disease, but involvement of the wrist is rare. To our knowledge there have been only 5 cases reported in the literature. The authors present a patient with Dupuytren's disease involving only the proximal palm and wrist who presented with functional limitation and a rapid clinical progression. PMID- 17336844 TI - Biomechanic comparison of the Teno Fix tendon repair device with the cruciate and modified Kessler techniques. AB - PURPOSE: To compare the mechanical behavior of a novel internal tendon repair device with commonly used 2-strand and 4-strand repair techniques for zone II flexor tendon lacerations. METHODS: Thirty cadaveric flexor digitorum profundus tendons were randomized to 1 of 3 core sutures: (1) cruciate locked 4-strand technique, (2) modified Kessler 2-strand core suture technique, or (3) Teno Fix multifilament wire tendon repair device. Each repair was tested in the load control setting on a Instron controller coupled to an MTS materials testing machine load frame by using an incremental cyclic linear loading protocol. A differential variable reluctance transducer was used to record displacement across the repair site. Cyclic force (n-cycles) to 1-mm gap and repair failure was recorded using serial digital photography. RESULTS: There was no significant difference in differential variable reluctance transducer displacement between the cruciate, modified Kessler, and Teno Fix repairs. The cruciate repair had greater resistance to visual 1-mm repair-site gap formation and repair-site failure when compared with the Kessler and Teno Fix repairs. No significant difference was found between the modified Kessler repair and the Teno Fix repair. In all specimens, the epitenon suture failed before the core suture. Repair failure occurred by suture rupture in the 7 cruciate specimens that failed, with evidence of gap formation before failure. Seven of 10 modified Kessler repairs failed by suture rupture. All of the Teno Fix repairs failed by pullout of the metal anchor. CONCLUSIONS: The Teno Fix repair system did not confer a mechanical advantage over the locked cruciate or modified Kessler suture techniques for zone II lacerations in cadaveric flexor tendons during cyclic loading in a linear testing model. This information may help to define safe boundaries for postoperative rehabilitation when using this internal tendon repair device. PMID- 17336845 TI - A loop-tendon suture for tendon transfer or graft surgery. AB - PURPOSE: We present a loop-tendon suture technique that was designed for easy tension adjustment and early postoperative rehabilitation in tendon transfer or graft surgeries. This study tested the biomechanical strength of the loop-tendon suture by using chicken flexor tendons and we report the preliminary clinical results. METHODS: We tested the ultimate strength of the loop-tendon suture against the end-weave suture technique in chicken flexor tendons. Forty flexor digitorum longus tendons of chickens were divided into 2 groups according to the suture technique, loop-tendon suture and end-weave suture groups, and then were subjected to linear loading in a tensile load testing machine. From 2000 to 2002 we performed 27 tendon transfer surgeries clinically, including 4 interpositional tendon grafts in 15 patients, using this technique followed by immediate passive motion exercise after surgery. The mean follow-up time was 20 months. RESULTS: The ultimate tensile load of chicken flexor tendons was 31 +/- 6 N for the loop tendon suture group and 23 +/- 8 N for the end-weave suture group, and the difference was statistically significant. Clinically, 6 patients with an extensor indicis proprius to an extensor pollicis longus transfer showed more than good results in the Geldmacher scheme. Three patients with an extensor indicis proprius to a central tendon transfer achieved proximal interphalangeal extension of less than 15 degrees of extension lag. One patient with a flexor digitorum profundus reconstruction obtained total active motion of 210 degrees. The 5 patients with triple transfers for radial nerve palsy showed more than neutral extension of the wrist and metacarpal joint. There were no tendon ruptures. CONCLUSIONS: The loop-tendon suture method has greater strength than the conventional end-weave technique, and can be used for secondary tendon reconstruction surgery with favorable clinical outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 17336846 TI - The early effects of sustained platelet-derived growth factor administration on the functional and structural properties of repaired intrasynovial flexor tendons: an in vivo biomechanic study at 3 weeks in canines. AB - PURPOSE: A bioactive fibrin-based delivery system was used to provide sustained administration of platelet-derived growth factor (PDGF-BB) in a clinically relevant model of intrasynovial flexor tendon repair. We hypothesized that PDGF BB administered in this manner would improve the sutured tendon's functional and structural properties 3 weeks after repair. METHODS: A delivery system consisting of 30 microL of fibrin matrix, peptide, heparin, and 100 ng of PDGF-BB was incorporated into the repair sites of randomly selected medial or lateral forepaw flexor digitorum profundus tendons of 8 adult mongrel dogs. The remaining forepaw flexor digitorum profundus tendons were repaired without the growth-factor and fibrin-based delivery system and served as controls. The surgically treated forelimbs were treated with controlled passive motion rehabilitation. The animals were killed at 3 weeks, at which time the tendons were tested for range of motion with a motion analysis system and for tensile properties with a materials testing machine. RESULTS: Proximal interphalangeal joint and distal interphalangeal joint rotation values were significantly higher for the PDGF-BB-treated tendons compared with the repair-alone tendons. Excursion values were also significantly higher in the PDGF-BB-treated tendons. There were no significant differences in tensile properties when comparing PDGF-BB-treated with repair-alone tendons. CONCLUSIONS: The functional properties of repaired intrasynovial flexor tendons were significantly improved with the sustained administration of PDGF-BB. The failure to achieve improvements in ultimate load, stiffness, and strain in the experimental group may have been due to suboptimal PDGF-BB dosage or suboptimal release kinetics. PMID- 17336847 TI - Community-associated methicillin-resistant Staphylococcus aureus hand infections in an urban setting. AB - PURPOSE: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection appears to be increasing. The purpose of this study was to determine prospectively the incidence of MRSA in community-associated hand infections in an urban hospital. METHODS: Sixty-one patients presented to our institution over a 9 month period with community-acquired hand infections that were evaluated and treated by the hand service. The specimens obtained during the initial evaluation and treatment were cultured and subjected to antibiotic susceptibility testing. Four nosocomial infections and 5 fight bites were excluded. RESULTS: Of the remaining 52 patients, 38 (73.1%) were MRSA positive. CONCLUSIONS: The rate of community-associated MRSA hand infections in an urban setting is higher than previously suspected. This should be taken into account when managing seemingly routine hand infections given that the treatment options are different for MRSA infections. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 17336848 TI - Mucormycosis of the upper extremity in a patient with alcoholic encephalopathy. AB - Cutaneous mucormycosis is a rare opportunistic infection caused by fungi of the class Zygomycetes that can be rapidly fatal if unrecognized. The diagnosis of this infection is often made by infectious disease, dermatologic, or intensive care specialists. Lesions that affect the upper limb may require a hand surgeon to diagnose the infection. The diagnosis may be difficult to make, because these infectious lesions can be confused with ischemic pathology. We report on a rare case of cutaneous mucormycosis caused by Rhizopus arrhizus in a patient with cirrhosis and renal failure who presented with an ischemic hand. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic V. PMID- 17336849 TI - Extraskeletal mesenchymal chondrosarcoma of the forearm: a case report. AB - Mesenchymal chondrosarcomas represent less than 10% of all chondrosarcomas. The majority of these tumors arise from the skeleton; only 22% have an extraosseous origin. Of the extraskeletal locations, the meninges, brain, and thigh are the most common. Involvement of the forearm is a rare occurrence. This case report describes an extraskeletal mesenchymal chondrosarcoma involving the forearm. PMID- 17336850 TI - A rare metastasis in the hand: a case of cutaneous metastasis of choriocarcinoma to the small finger. AB - Gestational choriocarcinoma is a malignant epithelial neoplasm of trophoblastic cells derived from any form of a previously normal or abnormal pregnancy. Choriocarcinoma is a rapidly invasive, widely metastasizing, malignant neoplasm. Hand and cutaneous metastases are rare and only one other report describing hand involvement was found in the literature. A 33-year-old woman was referred for evaluation of a papular lesion (6 x 4 mm) at the junction of the hyponychium and the nail bed of the dominant right small finger. At the time, she was being treated for choriocarcinoma with lung and brain metastases. Histopathology studies showed that the soft-tissue lesion from the patient's finger was a cutaneous metastasis of choriocarcinoma. PMID- 17336851 TI - Heterotopic nerve transfers: recent trends with expanding indication. AB - There has been increasing enthusiasm for heterotopic nerve transfers for brachial plexus palsy as well as peripheral mononeural dysfunction. The concept of nerve transfer surgery is not new; the first publications on the topic date back to the early 1900s. A wide variety of potential donor nerves are available including the intercostal nerves, the spinal accessory nerve, the phrenic nerve, the ipsilateral medial pectoral nerve, partial ulnar nerve, partial median nerve, thoracodorsal nerve, radial nerve to the triceps, and the ipsilateral C7 or the contralateral C7 nerve roots. Treatment strategies include avoidance of interposed nerve grafting, isolated motor recipient nerve, early transfer, neurorrhaphy close to target motor end plates, and similar diameter between donor nerve and recipient nerves. PMID- 17336852 TI - A technique to improve foot appearance after trimmed toe or hallux harvesting. AB - We describe a technique to improve the appearance of the donor site after hallux harvesting. The surgery has been used in 6 consecutive patients having a trimmed toe-type transfer. Instead of the classic stump closure advised by Wei, the following steps were performed on the donor site: (1) removal en bloc of the second metatarsal and transposition of the second toe on top of the proximal phalanx of the hallux, (2) interposition of a tibial (medial) glabrous flap from the tibial aspect of the hallux onto the tibial side of the second toe to increase its size, and (3) eponichial flap to increase the nail show on the second toe. Fixation of the toe was achieved with K-wires and cerclage wire. Crossed K-wires stabilized the first to the third metatarsals for 4 to 6 weeks. Ambulation with a stiff sole was allowed a few days after surgery. The main advantage of this technique is the improved donor site appearance. As a bonus, the amount of skin that can be harvested with the trimmed toe is slightly increased. The main drawback is that the number of toes is reduced to 4. PMID- 17336853 TI - Wrist denervation: anatomy of the anterior interosseous nerve and the innervation of the pronator quadratus. PMID- 17336854 TI - [Noninvasive markers of fibrosis: replacement for liver biopsy?]. PMID- 17336855 TI - [Drug treatment in type 2 diabetes (part 2)]. AB - Insulin secretagogues and insulin sensitizers can be combined with one another as well as with other treatments (described below). Alpha-glucosidase inhibitors delay intestinal absorption of carbohydrates and reduce postprandial glycemia. Orlistat and sibutramine improve insulin sensitivity by helping patients lose weight. Orlistat inhibits hydrolysis of dietary triglycerides. Sibutramine, a noradrenaline and serotonin reuptake inhibitor, reinforces feelings of satiety and increases energy expenditure. After approximately 10 years, insulin therapy is usually required together with oral antidiabetic agents (except glitazones) or alone if HbA(1c) (glycosylated hemoglobin) is>6.5%. New guidelines for management of type 2 diabetes were published in 2006. PMID- 17336856 TI - [Medical management of uncomplicated benign prostatic hyperplasia: a new decision algorithm]. AB - Management of benign prostatic hyperplasia (BPH) is currently undergoing profound changes. Medical treatment is not only symptomatic, but may also seek to modify the natural history of the disease, especially by reducing the risk of acute urinary retention. Medical treatment is no longer limited to a single drug: the combination of 2 different drugs from different treatment categories appears superior to single-drug treatment in some patients. Two instrumental techniques - microwave or radiofrequency thermotherapy, previously proposed as alternatives to surgery - are more appropriate as alternatives to medical treatment. These various items make it possible to construct a decision algorithm that is based at each stage on a decision shared with the patient. This algorithm to provide decision aid in management of uncomplicated symptomatic HBP takes initial disease indicators and other patient indicators into account together with its course under treatment, which has not previously been considered by international guidelines. PMID- 17336857 TI - [Myelodysplastic syndromes in adults]. AB - Myelodysplastic syndromes (MDS) are clonal hematological disorders characterized by ineffective hematopoiesis. Their increased prevalence is associated with the aging of the population. The aim of this article is to analyze the available literature about MDS - its classification, pathophysiology, prognosis and recent progress in treatment - and report our experience with it. Its diagnosis and classification are based on the morphological features of blood and bone marrow cells. The World Health Organization (WHO) working group has proposed a new classification to improve the homogeneity of the categories in the widely-used French-American-British classification in term of pathophysiology and prognosis. This new classification permits the consideration of clinical, etiologic, and cytogenetic data, including complex and heterogeneous cytogenetic abnormalities. The International Scoring System for evaluating Prognosis (IPSS), which has proven highly useful for this purpose, is a risk-based classification system for MDS, based on these cytogenetic abnormalities. It can be used to help guide therapeutic choices. For MDS with low IPSS scores (low-risk), appropriate treatment includes best supportive care, hematopoietic growth factors, and immunomodulatory drugs. For MDS with high IPSS scores, chemotherapy is appropriate at low or intense doses. For younger patients, allogeneic bone marrow transplantation, the only truly curative treatment, may be considered. Better understanding of the pathophysiology of MDS, including the role of oncogenes and various cytokines, is required to develop new treatments and treatment targets. The new classification and prognosis scoring system should lead to new therapeutic strategies that may modify the overall prognosis and quality of life of patients with MDS. PMID- 17336858 TI - [Magnetic resonance imaging of the brain]. AB - MRI uses the magnetic properties of the hydrogen atoms present in the human body. It presents no risks as long as the contraindications (pacemaker, metal fragment in the eye, pregnancy less than 3 months) are complied with. MRI is the reference imaging method for exploration of the brain. The contrast of these images depends on the type of sequence used. More specific sequences (diffusio-weighted, gradient echo) and gadolinium injection can be added to the basic sequences (T1, T2, Flair). PMID- 17336859 TI - [What's new in esophageal cancer treatment]. AB - The prognosis for esophageal cancer remains grim despite recent progress in diagnosis and treatment. Surgery is the standard treatment for stages I and II (only). Neoadjuvant chemotherapy or combined radiation and chemotherapy may be considered for stages IIb and III. Palliative surgery is no longer considered useful. Neoadjuvant or adjuvant radiation treatment does not improve survival. Adjuvant chemotherapy does not improve survival, and the benefits of its neoadjuvant use remain controversial in view of the discordant results. There is strong evidence that a neoadjuvant combination of radiation and chemotherapy improves resection and survival rates compared with surgery alone, but definitive proof is not currently available. Combined radiation and chemotherapy may be considered for locally advanced tumors in responding patients, with curative salvage surgery if the tumor persists. For patients whose tumor is inoperable, a combination of radiation and chemotherapy is the standard treatment. PMID- 17336860 TI - [Methodology for treatment evaluation: culture of doubt]. PMID- 17336861 TI - Out of order causes confusion. PMID- 17336862 TI - Editorial in the September 2006 issue of Pain Management Nursing. PMID- 17336863 TI - Clarification of December 2006 editorial, "Is There Anyone Out There?". PMID- 17336864 TI - Authorized and Unauthorized ("PCA by Proxy") Dosing of Analgesic Infusion Pumps: position statement with clinical practice recommendations. AB - The American Society for Pain Management Nursing (ASPMN), in order to address sentinel alerts issued by JCAHO in 2004 and ISMP in 2005 concerning "PCA by Proxy", has developed a position statement and clinical practice recommendations on Authorized and Unauthorized (PCA by Proxy) Dosing of Analgesic Infusion Pumps, approved by the Board of Directors in June of 2006. In short, ASPMN does not support the use of "PCA by Proxy". ASPMN does, however, support the practice of Authorized Agent Controlled Analgesia in a variety of patient care settings when the agency has in place clear guidelines outlining the conditions under which this practice shall be implemented and outlining monitoring procedures that will insure safe use of the therapy. In addition to outlining this position, the paper clarifies and distinguishes between the unsafe practice of "PCA by Proxy", in which unauthorized individuals activate the dosing button of an analgesic infusion pump for a patient receiving Patient Controlled Analgesia, and the safe practice of Authorized Agent Controlled Analgesia (AACA). Furthermore, the paper examines the ethical and safety issues and outlines the necessary screening and patient/family education needed to implement AACA. The position statement describes criteria for the use of AACA, guidelines for selection and education of the authorized agent, key prescription and monitoring recommendations during therapy, and quality improvement activities to insure safety and effectiveness. PMID- 17336866 TI - Experiences of expert nurses in caring for patients with postoperative pain. AB - Despite enormous technologic advances and substantial research in the area of pain management in recent years, numerous studies indicate that postoperative pain is not relieved in most patients. Nurses are the health care professionals who spend the most time with patients in pain. Despite this, there is a lack of research that has sought to understand the experiences of nurses, the professionals most closely tied to this issue. The purpose of this pilot qualitative study was to learn how expert nurses assess, manage, and care for patients with postoperative pain. A phenomenologic mode of inquiry was used to interview three expert nurse participants. Four themes emerged during the data analysis phase: considering the whole person, the independent art of nursing, accepting what the patient says, and commitment to surgical nursing. PMID- 17336865 TI - Patient experiences of pain and pain management at the end of life: a pilot study. AB - Cancer pain is a difficult symptom for patients to handle, causing patients extreme discomfort and a decreased quality of life. To support independent pain control for patients with refractory pain while staying in their home, an intrathecal approach for continuous pain management with patient-controlled extra doses from an external pump was implemented. Pain management was supported by a structured guideline for the nursing interventions: To enhance the understanding of how the patients experienced their pain and the continuous pain management at the end of life, a pilot study was conducted. The study followed a qualitative design with unstructured tape-recorded interviews. Three themes emerged from the analysis: (1) The pain was dreadful, reminding the patient of the cancer and the uncertainty of the future; (2) the need to reveal and conceal pain coexisted; and (3) the pain management and structured guideline contributed positively to gain a new perspective on health in which pain did not play the central role. The conclusion is that patients need to communicate their experiences of the pain to manage the pain adequately, while at the same time they need to conceal it to manage their everyday environment. Forthcoming research will focus on the relation between the pain and the way patients experience cancer and on the experience and specific needs of their family. PMID- 17336867 TI - Managing pain, managing ethics. AB - Noncompliance of family caregivers can present home hospice nurses with difficult ethical choices and powerful feelings about those choices. This is particularly so when family members do not adequately palliate their loved ones, resulting in treatable symptom distress during the dying process. This article presents a case study, moral analysis, and an evidence-based, practical plan of action for engaging family members of palliative care patients on a home hospice service. PMID- 17336868 TI - Videoconferencing for a veteran's pain management follow-up clinic. AB - The under treatment of pain has been well documented. Contributing to this is the limited availability of pain management specialists in many geographic areas. The use of technology to provide care to underserved areas is gaining momentum. We chose to study whether stable patients and staff in chronic pain clinic were satified with the use of a videoconferencing format in care delivery. Our goals were to determine whether patients and staff could successfully operate the extant videoconferencing equipment, was the equipment dependably functional, was the use of a videoconferencing format an acceptable method of healthcare delivery for both patients and staff, whether patients and staff were satisfied with the process, and whether this was a cost-effective mode of care delivery. Thirty-six patients were enrolled over 29 months. Questionnaires were administered to staff and patients. Routine pain clinic patient assessment tools were administered. Results showed the use of videoconferencing for this group of patients is useable and satisfactory for both patients and staff, that the patients save time and money, and that for a system where videoconferencing equipment is already in use, it is also cost effective. Staff were able to identify new patient problems. Some patients would prefer to be seen in person but find that the savings in time and money override this preference. Hearing impaired patients have difficulty using this medium. Dependable equipment and phone connections are needed. A videoconferencing clinic format is a clinically acceptable and cost effective method for follow-up of stable patients with chronic pain. PMID- 17336870 TI - Quality improvement for feeding assistance care in nursing homes. AB - Unintentional weight loss is a common problem among nursing home residents and one that can lead to adverse and costly clinical outcomes. Observational studies have shown that residents often receive inadequate and poor-quality feeding assistance during meals, and residents consume few calories between meals from oral liquid nutritional supplements or other food and fluid items. Improvements in the adequacy and quality of feeding assistance either during or between meals have been shown to improve residents' daily oral food and fluid consumption and promote weight gain. However, these feeding assistance interventions require significantly more time than nursing home staff currently spend on feeding assistance care activities. Alternative staffing models are explored through the recent federal "paid feeding assistant" regulation and an observational tool is described for use in practice to improve feeding assistance care. PMID- 17336871 TI - Infection control in long-term care facilities. AB - Infections are a common cause of morbidity and mortality in LTCF residents. For medical directors, infection prevention and control programs in LTCFs need to be proactive in identifying potential infectious disease threats and implementing appropriate infection control practices. Improving the initial evaluation of infections, the use of antimicrobial agents, and the implementation of hand hygiene and infection control precautions should be key focus areas for medical directors in order to prevent infections and control antibiotic resistance. PMID- 17336872 TI - Continuous quality improvement in nursing homes: public relations or a reality? PMID- 17336873 TI - A model quality improvement program for the management of falls in nursing homes. AB - There is an urgent need for model programs to effectively manage fall risk in nursing homes. Such programs should use best practices and quality improvement (QI) methodology in a manner that is practical for sustained implementation in the current resource-constrained long-term care environment. The Falls Management Program (FMP) represents 13 years of fieldwork (1993-2006). It is an interdisciplinary, multifaceted approach to reducing fall risk that includes systematic screening, assessment, individualized care planning, resident monitoring, and the elimination of environmental safety hazards. The FMP is initiated by a self-assessment process that assists nursing homes in identifying areas that need improvement so that staff can tailor implementation to their own facility's needs. The FMP incorporates education on best practices and uses several QI tools designed to assist nursing homes with program implementation. Core components of the program include administrative and clinical leadership, interdisciplinary teamwork using QI methodology, support by advance practice nurses, and an 8-step fall response system to facilitate the comprehensive investigation and documentation of falls, primary care provider involvement, and development of individualized fall risk reduction strategies. PMID- 17336874 TI - Implementing best practices in pressure ulcer care: the role of continuous quality improvement. PMID- 17336875 TI - Quality improvement initiatives for urinary incontinence in nursing homes. AB - Clinical practice guidelines based on research data and expert opinion provide more than adequate guidance for NHs to implement an incontinence quality improvement initiative that will meet the expectations laid out in the federal surveyor guidance for Tag F 315. All quality improvement initiatives take time, effort, leadership support, and coordination by a champion who is dedicated to program success. Simple policies, procedures, and documentation tools can be of critical value in improving the quality of incontinence care. While incontinence management may not be the highest priority for clinicians who care for NH residents suffering from numerous geriatric syndromes and medical conditions, a basic approach to assessment and targeted treatment can improve the quality of life of incontinent residents, prevent complications, improve family satisfaction with care, and facilitate the efficient use of staff resources for this labor intensive condition. PMID- 17336876 TI - Epidemiology of atrial fibrillation: a current perspective. AB - The prevalence of atrial fibrillation (AF) increases with age. Recent population based data indicate a trend of increasing incidence and prevalence of AF that is incompletely explained by an aging population. A recent population study estimated that the number of Americans afflicted by AF will increase from the current 2.3 million to more than 10 million by 2050. Novel risk factors--obesity and sleep apnea--may partially account for the current AF epidemic. Ethnic differences in the epidemiology of AF have been suggested but not clearly elucidated by population-based studies. The heritability of AF in the general population is strongly supported by population-based data. Genetic epidemiological studies on AF can potentially yield important mechanistic insights that may ultimately lead to novel preventative and therapeutic strategies. PMID- 17336877 TI - Reentry and atrial fibrillation. AB - The mechanisms of human atrial fibrillation (AF) are poorly understood. Experimental studies have demonstrated that cholinergic AF in the sheep heart is maintained by high-frequency reentrant sources (drivers) that result in a consistent left-to-right frequency gradient. More recently, clinical studies have confirmed the existence of a hierarchical organization in the rate of activation of different regions in the atria of patients with paroxysmal and chronic AF. Although maximal dominant-frequency sites were found to play a crucial role in the maintenance of AF in some patients, whether AF drivers in humans are focal or reentrant and whether changes in driver activity alter spatial frequency gradients are unclear. To test the hypothesis that localized functional reentry maintains AF in humans, we determined the effects of adenosine infusion on local dominant frequency at different sites of both atria. In patients with paroxysmal AF, adenosine infusion increases local dominant frequencies, particularly at the pulmonary vein-left atrial junction region, amplifying a left-to-right frequency gradient. In patients with chronic AF, dominant frequency is significantly higher than in patients with paroxysmal AF in all atrial regions surveyed, with the highest adenosine increase of frequencies outside the pulmonary vein region. Adenosine-induced driver acceleration is strongly suggestive of a reentrant mechanism in both groups of AF patients. PMID- 17336878 TI - Triggered activity and atrial fibrillation. AB - In 1999, Haissaguerre et al published a landmark article showing that atrial fibrillation can be initiated by electrical activity in the pulmonary veins. Not only does it appear that electrical activity in the veins initiates fibrillation, but it also may be responsible for perpetuating fibrillation. Subsequently, similar evidence has suggested that other thoracic veins (vena cavae, coronary sinus, ligament of Marshall) initiate and perpetuate atrial fibrillation. How does electrical impulse initiation occur in the veins? The results of numerous in vivo and in vitro studies on this subject have not conclusively defined a mechanism. Impulse initiation by automaticity and triggered activity as well as impulse initiation resulting from reentry have been suggested. In this article, we focus only on those data suggesting the possibility that triggered activity initiates and/or perpetuates atrial fibrillation. PMID- 17336880 TI - Management of atrial fibrillation in patients with heart failure. AB - Atrial fibrillation is a marker for worse outcomes in patients with heart failure and requires careful, individualized management. Anticoagulation and rate control are important. Routine use of antiarrhythmic drug therapy for maintenance of sinus rhythm carries concerns of risk and limited efficacy. Catheter ablation for maintaining sinus rhythm is feasible for some patients, but further studies are needed to define the risks and benefits. A role remains for AV junction ablation and pacing, with consideration of biventricular pacing to prevent dyssynchrony induced by chronic right ventricular pacing. Ongoing trials will continue to define the risks and benefits as these therapies evolve. PMID- 17336879 TI - Atrial fibrosis and the mechanisms of atrial fibrillation. AB - Atrial fibrillation (AF) is commonly associated with congestive heart failure (CHF), and CHF has been shown to be associated with atrial structural remodeling resulting in fibrosis. Atrial interstitial fibrosis has been seen in patients with CHF and in animal models of pacing-induced heart failure. With atrial fibrosis, conduction abnormalities result in increased AF vulnerability. The mechanism of AF associated with CHF is under debate, as both focal and reentrant mechanisms have been observed in animal models of CHF. However, recent studies using frequency-domain analysis have shown that the AF within this model is characterized by discrete, stable, high-frequency areas. The precise signaling processes involved in the development of atrial fibrosis are unknown. Angiotensin appears to play a role, as inhibition of angiotensin-converting enzyme (or angiotensin-receptor blocker) blunts atrial fibrosis in animal models of heart failure and decreases the incidence of AF in patients with heart failure. Transforming growth factor-beta (TGF-beta) also appears to play an important role. Mouse models that overexpress TGF-beta1 have profound atrial fibrosis and AF (with normal ventricles). Heart failure in canine models also produces increases in atrial TGF-beta1 expression, and inhibition of this expression prevents atrial fibrosis and the development of a substrate for AF. Atrial fibrosis appears to play a role in the development of a vulnerable substrate for AF, especially in the setting of CHF. PMID- 17336881 TI - Does cardiac resynchronization therapy reduce the incidence of atrial fibrillation, and does atrial fibrillation compromise the cardiac resynchronization therapy effect? PMID- 17336882 TI - Anticoagulation in atrial fibrillation: a contemporary viewpoint. AB - Anticoagulation therapy in patients with atrial fibrillation is important. This review consists of three parts: chronic anticoagulation, anticoagulation for cardioversion, and a brief comment on anticoagulation around the time of left atrial radiofrequency ablation. The risk stratification scheme of the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines for chronic anticoagulation is briefly reviewed. Although there are several other similar schemes, they are not identical. The key point is the balance between benefit and risk. Some emerging controversies are outlined. Two specific questions explored are: is well-controlled hypertension a risk factor, and does paroxysmal atrial fibrillation confer the same risk as continuous atrial fibrillation? Differences in the risk of bleeding while taking a vitamin K antagonist noted in recent compared with older data are discussed. Risk of bleeding in the elderly and combined antithrombotic therapy with a vitamin K antagonist and an antiplatelet agent in high-risk patients are briefly discussed. Recent failures of studies attempting to find a suitable alternative to vitamin K antagonists are outlined. The treatment guidelines for anticoagulation for cardioversion are briefly reviewed. The risk of thromboembolism according to international normalized ratio and use of low molecular-weight heparin as an alternative to warfarin are discussed. Anticoagulation before and after left atrial radiofrequency ablation is empirical, and long-term anticoagulation seems advisable for high risk patients at the present time. The two most pressing needs for further investigation are (1) clarification, simplification, and consolidated of risk stratification schemes and treatment recommendations and (2) discovery of alternatives to warfarin. PMID- 17336883 TI - Introduction to catheter ablation of atrial fibrillation: an overview. PMID- 17336884 TI - Lesion-forming technologies for catheter ablation of atrial fibrillation. PMID- 17336885 TI - Intracardiac atrial defibrillation. AB - Intravascular ventricular defibrillation and intravascular atrial defibrillation have many similarities. An important factor influencing the outcome of the shock is the potential gradient field created throughout the ventricles or the atria by the shock. A minimum potential gradient is required throughout the ventricles and probably the atria in order to defibrillate. The value of this minimum potential gradient is affected by several factors, including the duration, tilt, and number of phases of the waveform. For shock strengths near the defibrillation threshold, earliest activation following failed shocks arises in a region in which the potential gradient is low. The defibrillation threshold energy can be decreased by adding a third and even a fourth defibrillation electrode in regions where the shock potential gradient is low for the shock field created by the first two defibrillation electrodes and giving two sequential shocks, each through a different set of electrodes. However, the addition of more electrodes and sequential shocks complicates both the device and its implantation. Because patients are conscious when the atrial defibrillation shock is given, they experience pain during the shock, which is one of the main drawbacks of intravascular atrial defibrillation. Unfortunately, the pain threshold for defibrillation shocks is so low that a shock less than 1 J is uncomfortable and is not much less painful than shocks several times stronger. Therefore, even though electrode configurations exist that have lower atrial defibrillation threshold energy requirements than the atrial defibrillation threshold with standard defibrillation electrode configurations used in implantable cardioverter defibrillators (ICDs) for ventricular defibrillation, they are not clinically practical because their shocks are almost as painful as with the standard ICD electrode configurations. Such electrode configurations would make the ICD more complicated, leading to greater difficulty and longer time required for implantation. PMID- 17336886 TI - Autonomic nerves in pulmonary veins. AB - Rapid repetitive activities arising from pulmonary veins may initiate atrial fibrillation. The basis of these rapid repetitive activities remains unclear, but recent evidence suggests that the autonomic nervous system plays an important role in their formation. Pulmonary veins and the adjoining left atrium are highly innervated structures. This review summarizes recent developments in the understanding of the anatomy of autonomic nerves in and around pulmonary veins and their implications for atrial fibrillation. PMID- 17336887 TI - Autonomic nerve activity and atrial fibrillation. AB - This review focuses on the importance of autonomic nervous system (ANS) activity in the induction of paroxysmal atrial fibrillation (PAF). Clinical studies suggest that both sympathetic and parasympathetic nervous systems are important in mediating PAF. Consistent with that hypothesis, heart rate variability analyses showed that sympathovagal imbalance is present before the onset of PAF episodes. The importance of the ANS in PAF is further supported by animal experiments and recent clinical studies showing that vagal denervation enhances the efficacy of circumferential pulmonary vein ablation in preventing AF recurrence. In vitro studies show that ANS activation facilitates early afterdepolarization and triggered activity by simultaneously prolonging the intracellular calcium (Ca(i)) transient (sympathetic effect) and shortening the action potential duration (parasympathetic effect). By simultaneously mapping the membrane potential and Ca(i) transient in canine pulmonary vein during sympathetic stimulation, we demonstrated that spontaneous (voltage-independent) sarcoplasmic reticulum calcium release underlies the mechanisms of focal discharges. We developed and studied canine models of PAF induced by electrical, structural, and neural remodeling. We also have developed methods for long-term continuous recording of sympathetic and vagal nerve activity in ambulatory dogs. Preliminary results show that simultaneous sympathovagal discharges precede the onset of PAF in these dogs. ANS activity and Ca(i) transient dynamics are important in the development of PAF. These studies suggest that new methods or drugs aimed at modification of cardiac ANS activity may lead to new opportunities for AF control. PMID- 17336888 TI - Mapping and ablation of left atrial tachycardias occurring after atrial fibrillation ablation. AB - Regular left atrial tachycardias are a frequent complication of atrial fibrillation ablation procedures. The arrhythmia mechanism appears to be due to focal pulmonary vein reentry in patients who undergo only electrically guided pulmonary vein isolation. The most common site of origin is the septal and inferior aspect of the right pulmonary veins. Attention to avoiding gaps when ablating along this region will minimize the occurrence of these tachycardias. In patients who also undergo linear left atrial ablation lesions and in patients with significant left atrial disease, macroreentry around the mitral annulus or ipsilateral pulmonary veins is frequently observed. Confirming electrical block across any prophylactic linear lesions (mitral isthmus line, left atrial roof line) likely is important for preventing gap-related proarrhythmic tachycardias. When tachycardias do occur, temporizing with ventricular rate control and cardioversion is initially indicated, as approximately one third of these atrial tachycardias may resolve with time. For tachycardias persisting after ablation, detailed three-dimensional activation and entrainment mapping can facilitate localization of the atrial tachycardia and guide the approach to eliminating the arrhythmias. This review provides a systematic approach to the evaluation, diagnosis, localization, and elimination of left atrial tachycardias occurring after atrial fibrillation ablation. PMID- 17336889 TI - Patterns of activation in human atrial fibrillation. AB - The electrophysiological properties within the pulmonary vein (PV) and PV-left atrial (LA) junction were evaluated using a basket catheter in patients with paroxysmal atrial fibrillation. The effective refractory period of the distal PV was significantly shorter than that of the PV-LA junction. The conduction delay from the distal to proximal PV was significantly longer than that from the proximal to distal PV. During initiation of AF, a reentry involving exit and entrance breakthrough points at the PV-LA junction was observed. The presence of anisotropic conduction properties at the PV-LA junction may be critical to promote reentry formation. PMID- 17336890 TI - Pulmonary vein antrum isolation. AB - Pulmonary vein antrum isolation offers safe and effective treatment of atrial fibrillation by eliminating the potential triggers of this arrhythmia. The pulmonary vein antra encompass, in addition to the pulmonary veins, the left atrial roof and posterior wall and, in the case of the right pulmonary vein antra, a portion of the interatrial septum. Compared with pulmonary vein ostial isolation, this technique offers a higher success rate and a lower complication rate. In patients with nonparoxysmal atrial fibrillation, extension of septal ablation to the region of the mitral annulus is associated with better outcomes. Further adjunctive strategies include ablation in the coronary sinus, atrial side of inferior mitral annulus, superior vena cava, and along the cristae terminalis, targeting complex fragmented electrograms. We usually reserve these adjunctive ablative therapies for patients with persistent or chronic atrial fibrillation and those with unsuccessful prior catheter ablation. PMID- 17336891 TI - Atrioventricular node modification and ablation for ventricular rate control in atrial fibrillation. PMID- 17336892 TI - Pacing therapy for prevention of atrial fibrillation. AB - The role of permanent pacing for the prevention of atrial fibrillation is reviewed. A moderate decrease in the incidence of acute and chronic atrial fibrillation has been seen with atrial pacing compared with ventricular pacing, especially in patients with sinus node dysfunction based on a meta-analysis of clinical trials. A variety of different pacing algorithms have been studied in small numbers of patients for only short durations of time and have shown an inconsistent effect on different measures of atrial fibrillation burden. The interatrial septum or Bachmann's bundle has been shown in some, but not all, studies to have a beneficial effect on reducing the incidence of atrial fibrillation. Less well studied is the combined benefit of alternate site atrial pacing combined with atrial fibrillation prevention pacing algorithms. Device measurement of the duration of atrial fibrillation appears to be an accurate measure of disease burden, and preliminary evidence suggests that atrial fibrillation burden is associated with an increased risk of stroke and death. Future studies are needed to demonstrate the long-term efficacy of device algorithms for the prevention or termination of atrial fibrillation. PMID- 17336893 TI - Nonantiarrhythmic drug therapy for atrial fibrillation. AB - Recent studies have begun to elucidate the molecular mechanisms that promote the generation and progressive nature of atrial fibrillation. Evidence from both experimental and clinical investigations has implicated an important role for the renin-angiotensin-aldosterone system, inflammation, and oxidative stress, with data that suggest a potential beneficial effect for angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists, antiinflammatory agents, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), and omega-3 polyunsaturated fatty acids. In addition, compounds that increase gap junctional conductance or that block 5 hydroxytryptamine-4 receptors have also shown promise in the experimental setting. Large-scale, prospective clinical trials will clarify the utility of these new therapeutic approaches to prevent atrial fibrillation in specific clinical settings. PMID- 17336894 TI - Medical management of atrial fibrillation: future directions. AB - Atrial fibrillation is the most common arrhythmia that requires treatment, and although ablation is appropriate in many cases, anti-arrhythmic drug therapy remains the first and most appropriate therapy in most patients. Currently available antiarrhythmic drugs are limited by modest efficacy and significant toxicity. Cardiac toxicity relates to effects on the ventricle, especially in prolonging the QT interval and causing torsades de pointes. Amiodarone, an agent with multiple antiarrhythmic effects, is unique in its relative lack of pro arrhythmia, although its non-cardiac toxicities limit its use. Some investigational agents are directed at multiple ion channels, or are designed to be analogs of amiodarone. The other line of investigation focuses on the antiarrhythmic action of agents that affect novel ion channel targets. Basic and early clinical studies show promise for drugs that provide atrial antiarrhythmic effects without ventricular pro-arrhythmia by affecting the atrium preferentially or selectively (inhibiting the I(TO) and I(Kur) currents, respectively). Future drugs may possess preferential effects on the remodeled atrium (and as such would be selective for patients with atrial fibrillation). It is hoped that efforts to develop new drugs, including those with preferential effects on the atrium, will provide therapy with greater efficacy and safety. PMID- 17336895 TI - Apelin and its g protein-coupled receptor regulate cardiac development as well as cardiac function. AB - The Apelin pathway has only recently emerged as an important regulator of cardiac and vascular function, mediating adaptation to physiological stress and disease. In this issue of Developmental Cell, experiments in zebrafish convincingly show a critical role for this pathway in myocardial cell specification and heart development. PMID- 17336896 TI - Special delivery: dynamic targeting via cortical capture of microtubules. AB - Gap junction formation depends on the proper transport of connexin hemichannels to sites of cell-cell contact. Recently in Cell, Shaw et al. implicate microtubule tip tracking proteins in the trafficking of connexin43 to adherens junctions (Shaw et al., 2007). This finding suggests a mechanism for targeted delivery of membrane proteins by microtubule capture at the cortex. PMID- 17336897 TI - A smell to die for. AB - How dietary restriction extends life span may involve anticipatory neurons. The odor of dietary yeast is sufficient to speed Drosophila aging while mutants of an odorant-binding protein extend life span. PMID- 17336898 TI - "Smad"eningly erratic: target gene methylation determines whether TGFbeta promotes or suppresses malignant glioma. AB - TGFbeta functions as a tumor suppressor in some contexts and a tumor promoter in others. In a recent issue of Cancer Cell, Bruna et al. (2007) shed light on an epigenetic mechanism that underlies this schizophrenic behavior in malignant glioma. Their findings highlight a stem cell/cancer link...and a potential blind spot in large-scale cancer genome sequencing projects. PMID- 17336899 TI - COP sets TRAPP for vesicles. AB - Intracellular transport vesicles identify their destination by a poorly understood process termed tethering. Recent work shows that in addition to its role in membrane-cargo selection, the COPII vesicle coat recruits TRAPPI, a cytosolic protein complex required for vesicle tethering. PMID- 17336900 TI - Nuclear architecture--an island no more. AB - The eukaryotic nucleus has been the neglected child of cell biology. The "International Symposium on Functional Organization of the Nucleus" held in January on Awaji Island, Japan, highlighted recent work on nuclear organization and function. Emerging from this conference was a holistic view in which diverse chemical and physical signals link the nuclear and cytoplasmic compartments of cells. PMID- 17336902 TI - Organization of interphase microtubules in fission yeast analyzed by electron tomography. AB - Polarized cells, such as neuronal, epithelial, and fungal cells, all display a specialized organization of their microtubules (MTs). The interphase MT cytoskeleton of the rod-shaped fission yeast, Schizosaccharomyces pombe, has been extensively described by fluorescence microscopy. Here, we describe a large scale, electron tomography investigation of S. pombe, including a 3D reconstruction of a complete eukaryotic cell volume at sufficient resolution to show both how many MTs there are in a bundle and their detailed architecture. Most cytoplasmic MTs are open at one end and capped at the other, providing evidence about their polarity. Electron-dense bridges between the MTs themselves and between MTs and the nuclear envelope were frequently observed. Finally, we have investigated structure/function relationships between MTs and both mitochondria and vesicles. Our analysis shows that electron tomography of well preserved cells is ideally suited for describing fine ultrastructural details that were not visible with previous techniques. PMID- 17336901 TI - A Wnt-CKIvarepsilon-Rap1 pathway regulates gastrulation by modulating SIPA1L1, a Rap GTPase activating protein. AB - Noncanonical Wnt signals control morphogenetic movements during vertebrate gastrulation. Casein kinase I epsilon (CKIvarepsilon) is a Wnt-regulated kinase that regulates Wnt/beta-catenin signaling and has a beta-catenin-independent role(s) in morphogenesis that is poorly understood. Here we report the identification of a CKIvarepsilon binding partner, SIPA1L1/E6TP1, a GAP (GTPase activating protein) of the Rap small GTPase family. We show that CKIvarepsilon phosphorylates SIPA1L1 to reduce its stability and thereby increase Rap1 activation. Wnt-8, which activates CKIvarepsilon, enhances the CKIvarepsilon dependent phosphorylation and degradation of SIPA1L1. In early Xenopus or zebrafish development, inactivation of the Rap1 pathway results in abnormal gastrulation and a shortened anterior-posterior axis. Although CKIvarepsilon also transduces Wnt/beta-catenin signaling, inhibition of Rap1 does not alter beta catenin-regulated gene expression. Our data demonstrate a role for CKIvarepsilon in noncanonical Wnt signaling and indicate that Wnt regulates morphogenesis in part through CKIvarepsilon-mediated control of Rap1 signaling. PMID- 17336903 TI - Yeast mitochondrial division and distribution require the cortical num1 protein. AB - Yeast mitochondrial division requires the dynamin-related Dnm1 protein. By isolating high-copy suppressors of a dominant-negative Dnm1p mutant, we uncovered an unexpected role in mitochondrial division and inheritance for Num1p, a protein previously shown to facilitate nuclear migration. num1 mutants contain an interconnected network of mitochondrial tubules, remarkably similar to cells lacking Dnm1p, and time-lapse microscopy confirms that mitochondrial fission is greatly reduced in num1Delta cells. We also find that Num1p assembles into punctate structures, which often colocalize with mitochondrial-bound Dnm1p particles. Suggesting a role for both Num1p and Dnm1p in mitochondrial inheritance, we find that num1 dnm1 double mutants accumulate mitochondria in daughter buds and that mother cells are frequently devoid of all mitochondria. Thus, our studies have revealed an additional role for Dnm1p in mitochondrial transmission through its interaction with Num1p, thereby providing a link between mitochondrial division and inheritance. PMID- 17336904 TI - MEF2C transcription factor controls chondrocyte hypertrophy and bone development. AB - Chondrocyte hypertrophy is essential for endochondral bone development. Unexpectedly, we discovered that MEF2C, a transcription factor that regulates muscle and cardiovascular development, controls bone development by activating the gene program for chondrocyte hypertrophy. Genetic deletion of Mef2c or expression of a dominant-negative MEF2C mutant in endochondral cartilage impairs hypertrophy, cartilage angiogenesis, ossification, and longitudinal bone growth in mice. Conversely, a superactivating form of MEF2C causes precocious chondrocyte hypertrophy, ossification of growth plates, and dwarfism. Endochondral bone formation is exquisitely sensitive to the balance between MEF2C and the corepressor histone deacetylase 4 (HDAC4), such that bone deficiency of Mef2c mutant mice can be rescued by an Hdac4 mutation, and ectopic ossification in Hdac4 null mice can be diminished by a heterozygous Mef2c mutation. These findings reveal unexpected commonalities in the mechanisms governing muscle, cardiovascular, and bone development with respect to their regulation by MEF2 and class II HDACs. PMID- 17336905 TI - Apelin and its receptor control heart field formation during zebrafish gastrulation. AB - The vertebrate heart arises during gastrulation as cardiac precursors converge from the lateral plate mesoderm territories toward the embryonic midline and extend rostrally to form bilateral heart fields. G protein-coupled receptors (GPCRs) mediate functions of the nervous and immune systems; however, their roles in gastrulation remain largely unexplored. Here, we show that the zebrafish homologs of the Agtrl1b receptor and its ligand, Apelin, implicated in physiology and angiogenesis, control heart field formation. Zebrafish gastrulae express agtrl1b in the lateral plate mesoderm, while apelin expression is confined to the midline. Reduced or excess Agtrl1b or Apelin function caused deficiency of cardiac precursors and, subsequently, the heart. In Apelin-deficient gastrulae, the cardiac precursors converged inefficiently to the heart fields and showed ectopic distribution, whereas cardiac precursors overexpressing Apelin exhibited abnormal morphology and rostral migration. Our results implicate GPCR signaling in movements of discrete cell populations that establish organ rudiments during vertebrate gastrulation. PMID- 17336906 TI - The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors. AB - While many factors that modulate the morphogenesis and patterning of the embryonic heart have been identified, relatively little is known about the molecular events that regulate the differentiation of progenitor cells fated to form the myocardium. Here, we show that zebrafish grinch (grn) mutants form a reduced number of myocardial progenitor cells, which results in a profound deficit in cardiomyocyte numbers in the most severe cases. We show that grn encodes the G protein-coupled receptor (GPCR) Agtrl1b, a known regulator of adult cardiovascular physiology. Ectopic expression of Apelin, an Agtrl1b ligand, results in the complete absence of cardiomyocytes. Data from transplantation and transgenic approaches indicate that Agtrl1 signaling plays a cell-autonomous role in myocardial specification, with activity being required coincident with the onset of gastrulation movements. These results support a model in which agtrl1b regulates the migration of cells fated to form myocardial progenitors. PMID- 17336907 TI - Notch signaling is essential for ventricular chamber development. AB - Ventricular chamber morphogenesis, first manifested by trabeculae formation, is crucial for cardiac function and embryonic viability and depends on cellular interactions between the endocardium and myocardium. We show that ventricular Notch1 activity is highest at presumptive trabecular endocardium. RBPJk and Notch1 mutants show impaired trabeculation and marker expression, attenuated EphrinB2, NRG1, and BMP10 expression and signaling, and decreased myocardial proliferation. Functional and molecular analyses show that Notch inhibition prevents EphrinB2 expression, and that EphrinB2 is a direct Notch target acting upstream of NRG1 in the ventricles. However, BMP10 levels are found to be independent of both EphrinB2 and NRG1 during trabeculation. Accordingly, exogenous BMP10 rescues the myocardial proliferative defect of in vitro-cultured RBPJk mutants, while exogenous NRG1 rescues differentiation in parallel. We suggest that during trabeculation Notch independently regulates cardiomyocyte proliferation and differentiation, two exquisitely balanced processes whose perturbation may result in congenital heart disease. PMID- 17336908 TI - Hindsight mediates the role of notch in suppressing hedgehog signaling and cell proliferation. AB - Temporal and spatial regulation of proliferation and differentiation by signaling pathways is essential for animal development. Drosophila follicular epithelial cells provide an excellent model system for the study of temporal regulation of cell proliferation. In follicle cells, the Notch pathway stops proliferation and promotes a switch from the mitotic cycle to the endocycle. Here, we show that zinc-finger transcription factor Hindsight mediates the role of Notch in regulating cell differentiation and the switch of cell-cycle programs. Hindsight is required and sufficient to stop proliferation and induce the transition to the endocycle. To do so, it represses string, Cut, and Hedgehog signaling, which promote proliferation during early oogenesis. Hindsight, along with another zinc finger protein, Tramtrack, downregulates Hedgehog signaling through transcriptional repression of cubitus interruptus. Our studies suggest that Hindsight bridges the two antagonistic pathways, Notch and Hedgehog, in the temporal regulation of follicle-cell proliferation and differentiation. PMID- 17336909 TI - DRE-1: an evolutionarily conserved F box protein that regulates C. elegans developmental age. AB - During metazoan development, cells acquire both positional and temporal identities. The Caenorhabditis elegans heterochronic loci are global regulators of larval temporal fates. Most encode conserved transcriptional and translational factors, which affect stage-appropriate programs in various tissues. Here, we describe dre-1, a heterochronic gene, whose mutant phenotypes include precocious terminal differentiation of epidermal stem cells and altered temporal patterning of gonadal outgrowth. Genetic interactions with other heterochronic loci place dre-1 in the larval-to-adult switch. dre-1 encodes a highly conserved F box protein, suggesting a role in an SCF ubiquitin ligase complex. Accordingly, RNAi knockdown of the C. elegans SKP1-like homolog SKR-1, the cullin CUL-1, and ring finger RBX homologs yielded similar heterochronic phenotypes. DRE-1 and SKR-1 form a complex, as do the human orthologs, hFBXO11 and SKP1, revealing a phyletically ancient interaction. The identification of core components involved in SCF-mediated modification and/or proteolysis suggests an important level of regulation in the heterochronic hierarchy. PMID- 17336910 TI - Temporal control of neurogenin3 activity in pancreas progenitors reveals competence windows for the generation of different endocrine cell types. AB - All pancreatic endocrine cells, producing glucagon, insulin, somatostatin, or PP, differentiate from Pdx1+ progenitors that transiently express Neurogenin3. To understand whether the competence of pancreatic progenitors changes over time, we generated transgenic mice expressing a tamoxifen-inducible Ngn3 fusion protein under the control of the pdx1 promoter and backcrossed the transgene into the ngn3(-/-) background, devoid of endogenous endocrine cells. Early activation of Ngn3-ER(TM) almost exclusively induced glucagon+ cells, while depleting the pool of pancreas progenitors. As from E11.5, Pdx1+ progenitors became competent to differentiate into insulin+ and PP+ cells. Somatostatin+ cells were generated from E14.5, while the competence to make glucagon+ cells was dramatically decreased. Hence, pancreas progenitors, similar to retinal or cortical progenitors, go through competence states that each allow the generation of a subset of cell types. We further show that the progenitors acquire competence to generate late-born cells in a mechanism that is intrinsic to the epithelium. PMID- 17336911 TI - Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. AB - Stem cell asymmetric division requires tight control of spindle orientation. To study this key process, we have recorded Drosophila larval neural stem cells (NBs) engineered to express fluorescent reporters for microtubules, pericentriolar material (PCM), and centrioles. We have found that early in the cell cycle, the two centrosomes become unequal: one organizes an aster that stays near the apical cortex for most of the cell cycle, while the other loses PCM and microtubule-organizing activity, and moves extensively throughout the cell until shortly before mitosis when, located near the basal cortex, it recruits PCM and organizes the second mitotic aster. Upon division, the apical centrosome remains in the stem cell, while the other goes into the differentiating daughter. Apical aster maintenance requires the function of Pins. These results reveal that spindle orientation in Drosophila larval NBs is determined very early in the cell cycle, and is mediated by asymmetric centrosome function. PMID- 17336912 TI - Limits for survivability in frontal collisions: theory and real-life data combined. AB - The limits for survivability in vehicle frontal collisions are unknown. This paper proposes a new hypothesis that occupant risk in frontal collisions is due to both inertial and crushing injuries and that the limits of survivability in frontal collisions are principally due to the complete crushing of vehicles at high DeltaV's. Analysis of the NASS data for the period 1982-1991 for AIS3+ injury and fatality to belted and unbelted drivers shows that the real world distributions of risk with DeltaV are asymptotic to 1.0 over similar DeltaV ranges and over a lower speed range than that predicted from intrusion/complete car crush alone. This is consistent with the proposed hypothesis as human biomechanical loading also influences survivability. While the hypothesis is supported by the presently available limited high-speed collision data, further in-depth investigations should be undertaken to confirm the ultimate limits of survivability. PMID- 17336913 TI - Central retinal sensitivity measured with the micro perimeter 1 after photodynamic therapy for polypoidal choroidal vasculopathy. AB - PURPOSE: To evaluate central retinal sensitivity and its relation to the symptomatic change noted in central visual disturbance shortly after photodynamic therapy (PDT) in eyes with polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective interventional case series. METHODS: We reviewed retrospectively 20 eyes of 20 patients who underwent PDT for the treatment of subfoveal PCV. Microperimetry in the macular area was performed with Micro Perimeter 1 (MP1) [Nidek, Vigonza, Italy] before and at one, three, and six months after PDT. Forty measurement points were located within the central 10 degree of the macula. RESULTS: After PDT, although most eyes showed a reduction in exudation, the mean posttreatment visual acuity did not change significantly. At one month after PDT, however, retinal sensitivities within the central 2 degree, 6 degree, and 10 degree fields, which were 3.6 +/- 3.1, 5.1 +/- 3.4, and 6.2 +/- 3.6 dB [decibels] at baseline, improved to 5.9 +/- 3.8 (P = .003), 7.1 +/- 3.6 (P = .003), and 8.1 +/- 3.5 dB (P = .004). At one month after treatment, 14 patients (70%) noted subjective improvement of the central visual disturbance and mean retinal sensitivity within the central 2 degree, 6 degree, and 10 degree fields had improved more than 2 dB in 11, 10, and eight eyes, respectively. At three and six months after PDT, however, postoperative improvement of the retinal sensitivities was diminished. CONCLUSIONS: Retinal sensitivity in the macular area of eyes with subfoveal PCV improved shortly after PDT, and may account, at least in part, for the immediate subjective improvement in central vision after PDT. PMID- 17336914 TI - Detection of early hydroxychloroquine retinal toxicity enhanced by ring ratio analysis of multifocal electroretinography. AB - PURPOSE: To assess decreased retinal function associated with high cumulative doses of hydroxychloroquine using multifocal electroretinography (mfERG). DESIGN: Retrospective cross-sectional study. METHODS: Sixty-two patients referred for evaluation of hydroxychloroquine retinal toxicity. Controls were 67 normal eyes of 67 patients referred for a variety of conditions in the other eye. Visual symptoms, duration of treatment, daily hydroxychloroquine dose (milligrams and milligrams per kilogram), cumulative dose, condition for which the drug was taken, visual acuity, retinal examination, visual fields, and mfERG amplitude. The average mfERG amplitude was calculated for five concentric rings. The age corrected amplitude of the central hexagon (R(1)) and the ratios of R(1) to each of the other rings (e.g., R(1)/R(2), R(1)/R(3)) were compared with limits derived from control eyes. RESULTS: The incidence of characteristic mfERG abnormalities in patients referred for evaluation with cumulative hydroxychloroquine doses of more than 1250 g was nearly 50%. It was 2.8 times that found in patients with cumulative doses less than 1250 g. Significant abnormalities were seen with cumulative doses as low as 400 g. The mfERG abnormality most commonly detected was an increased R(1)/R(2) ratio. Cumulative dose was more predictive of mfERG abnormalities than daily dose (either in milligrams or milligrams per kilogram) or duration of treatment. CONCLUSIONS: Functional testing of the retina with mfERG shows locally decreased retinal function in a large fraction of patients referred for evaluation who have taken high cumulative doses of hydroxychloroquine. A prudent mfERG testing strategy is proposed. PMID- 17336915 TI - A cell-based nitric oxide reporter assay useful for the identification and characterization of modulators of the nitric oxide/guanosine 3',5'-cyclic monophosphate pathway. AB - Nitric oxide (NO) plays an important role in protection against the onset and progression of various cardiovascular disorders. Therefore, the NO/guanosine 3',5'-cyclic monophosphate (cGMP) pathway has gained considerable attention and has become a target for new drug development. We have established a rapid, homogeneous, cell-based, and highly sensitive reporter assay for NO generated by endothelial nitric oxide synthase (eNOS). In a coculture system, NO production is indirectly monitored in living cells via soluble guanylyl cyclase (sGC) activation and calcium influx mediated by the olfactory cyclic nucleotide-gated (CNG) cation channel CNGA2, acting as the intracellular cGMP sensor. Using this NO reporter assay, we performed a fully automated high-throughput screening campaign for stimulators of NO synthesis. The coculture system reflects most aspects of the natural NO/cGMP pathway, namely, Ca(2+)-dependent and Ca(2+) independent regulation of eNOS activity by G protein-coupled receptor agonists, oxidative stress, phosphorylation, and cofactor availability as well as NO mediated stimulation of cGMP synthesis by sGC activation. The NO reporter assay allows the real-time detection of NO synthesis within living cells and makes it possible to identify and characterize activators and inhibitors of enzymes involved in the NO/cGMP signaling pathway. PMID- 17336916 TI - [The conventional hearing aid]. AB - The conventional hearing aid has benefited from the progress made in electronic miniaturization and digital signal processing. The prescriber should be familiar with these improvements, the anatomic and acoustic limitations related to hearing aids, the possibilities of surgical rehabilitation, as well as the indications for other auditive rehabilitation techniques (bone conduction hearing, middle ear implant, and cochlear implant). A hearing aid should be prescribed within a precise context taking into account patient history, clinical examination, audiometric testing, and choice of the device. Optimal management of a hearing device for a child should be conducted within an adapted network including a specialized ENT physician, audiophonology, a qualified hearing prosthetist, a speech therapist, etc.). PMID- 17336917 TI - [Mandibular reconstruction with osseous free flaps: functional results]. AB - OBJECTIVES: The aim of this retrospective study is to evaluate functional results of oromandibular reconstruction with osseous free flaps. MATERIAL AND METHODS: A total of 67 patients who underwent oromandibular reconstruction with fibula (n=60) or scapular (n=7) free flap between 2000 and 2004 were included in this study. We analysed functional results (alimentation, elocution, mouth opening and cosmetic appearance) and researched the potentially predictive factors of these results (age, comorbidity, preoperative irradiation, type of defect...; Chi(2) test). RESULTS: The rate of free flap success was 89.6%. A functional result considered as normal or subnormal was obtained by more than 50% of patients. Oral alimentation (without tube feeding) and intelligible speech were recovered by 92.5% of patients. Through and through defects and free flap failures were determinant predictive factors of worse functional outcomes. CONCLUSION: Fibula free flap is considered as the flap of choice for oromandibular reconstruction and allows excellent functional results. PMID- 17336918 TI - [Otoacoustic emissions in clinical and surgical practice]. AB - OBJECTIVES: Otoacoustic emissions (OAEs), discovered in 1978, have a well established cochlear origin. They strongly depend on the outer hair cells and are widely used in experimental research as a means for testing cochlear function. However, outside screening, OAEs are only rarely used in clinical practice. The objective of this paper was to show their vast clinical utility. MATERIAL AND METHODS: First, a review of the biophysical and physiological knowledge on OAEs is provided, concerning transient OAEs as well as distortion-product OAEs, recalling the origin and the meanings of these acoustic signals. Several clinical situations are then presented, and the corresponding OAE alterations are explained, such as hearing screening in neonates, diagnosis of hearing impairment with particularities related to the age of the patient, situations critical to the cochlea such as ototoxic treatments, and surgical procedures to the cerebellopontine angle. RESULTS: OAEs appear to be a powerful tool in clinical practice, particularly in hearing screening and diagnosis of deafness. They can also be used to monitor hearing function during cerebellopontine angle tumor resection. CONCLUSION: OAEs are still rarely used as a diagnostic tool by clinicians despite their clinical value, which should make them a primary choice. PMID- 17336919 TI - A cluster of carboxylic groups in PsbO protein is involved in proton transfer from the water oxidizing complex of Photosystem II. AB - The hypothesis presented here for proton transfer away from the water oxidation complex of Photosystem II (PSII) is supported by biochemical experiments on the isolated PsbO protein in solution, theoretical analyses of better understood proton transfer systems like bacteriorhodopsin and cytochrome oxidase, and the recently published 3D structure of PS II (Pdb entry 1S5L). We propose that a cluster of conserved glutamic and aspartic acid residues in the PsbO protein acts as a buffering network providing efficient acceptors of protons derived from substrate water molecules. The charge delocalization of the cluster ensures readiness to promptly accept the protons liberated from substrate water. Therefore protons generated at the catalytic centre of PSII need not be released into the thylakoid lumen as generally thought. The cluster is the beginning of a localized, fast proton transfer conduit on the lumenal side of the thylakoid membrane. Proton-dependent conformational changes of PsbO may play a role in the regulation of both supply of substrate water to the water oxidizing complex and the resultant proton transfer. PMID- 17336920 TI - Changes in cyclic and respiratory electron transport by the movement of phycobilisomes in the cyanobacterium Synechocystis sp. strain PCC 6803. AB - Phycobilisomes (PBS) are the major accessory light-harvesting complexes in cyanobacteria and their mobility affects the light energy distribution between the two photosystems. We investigated the effect of PBS mobility on state transitions, photosynthetic and respiratory electron transport, and various fluorescence parameters in Synechocystis sp. strain PCC 6803, using glycinebetaine to immobilize and couple PBS to photosystem II (PSII) or photosystem I (PSI) by applying under far-red or green light, respectively. The immobilization of PBS at PSII inhibited the increase in cyclic electron flow, photochemical and non-photochemical quenching, and decrease in respiration that occurred during the movement of PBS from PSII to PSI. In contrast, the immobilization of PBS at PSI inhibited the increase in respiration and photochemical quenching and decrease in cyclic electron flow and non photochemical quenching that occurred when PBS moved from PSI to PSII. Linear electron transport did not change during PBS movement but increased or decreased significantly during longer illumination with far-red or green light, respectively. This implies that PBS movement is completed in a short time but it takes longer for the overall photosynthetic reactions to be tuned to a new state. PMID- 17336921 TI - Quantum mechanical calculations of charge effects on gating the KcsA channel. AB - A series of ab initio (density functional) calculations were carried out on side chains of a set of amino acids, plus water, from the (intracellular) gating region of the KcsA K(+) channel. Their atomic coordinates, except hydrogen, are known from X-ray structures [D.A. Doyle, J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, R. MacKinnon, The structure of the potassium channel: molecular basis of K(+) conduction and selectivity, Science 280 (1998) 69-77; R. MacKinnon, S.L. Cohen, A. Kuo, A. Lee, B.T. Chait, Structural conservation in prokaryotic and eukaryotic potassium channels, Science 280 (1998) 106-109; Y. Jiang, A. Lee, J. Chen, M. Cadene, B.T. Chait, R. MacKinnon, The open pore conformation of potassium channels. Nature 417 (2001) 523-526], as are the coordinates of some water oxygen atoms. The 1k4c structure is used for the starting coordinates. Quantum mechanical optimization, in spite of the starting configuration, places the atoms in positions much closer to the 1j95, more tightly closed, configuration. This state shows four water molecules forming a "basket" under the Q119 side chains, blocking the channel. When a hydrated K(+) approaches this "basket", the optimized system shows a strong set of hydrogen bonds with the K(+) at defined positions, preventing further approach of the K(+) to the basket. This optimized structure with hydrated K(+) added shows an ice like 12 molecule nanocrystal of water. If the water molecules exchange, unless they do it as a group, the channel will remain blocked. The "basket" itself appears to be very stable, although it is possible that the K(+) with its hydrating water molecules may be more mobile, capable of withdrawing from the gate. It is also not surprising that water essentially freezes, or forms a kind of glue, in a nanometer space; this agrees with experimental results on a rather different, but similarly sized (nm dimensions) system [K.B. Jinesh, J.W.M. Frenken, Capillary condensation in atomic scale friction: how water acts like a glue, Phys. Rev. Lett. 96 (2006) 166103/1-4]. It also agrees qualitatively with simulations on channels [A. Anishkin, S. Sukharev, Water dynamics and dewetting transitions in the small mechanosensitive channel MscS, Biophys. J. 86 (2004) 2883-2895; O. Beckstein, M.S.P. Sansom, Liquid-vapor oscillations of water in hydrophobic nanopores, Proc. Natl Acad. Sci. U. S. A. 100 (2003) 7063-7068] and on featureless channel-like systems [J. Lu, M.E. Green, Simulation of water in a pore with charges: application to a gating mechanism for ion channels, Prog. Colloid Polym. Sci. 103 (1997) 121-129], in that it forms a boundary on water that is not obvious from the liquid state. The idea that a structure is stable, even if individual molecules exchange, is well known, for example from the hydration shell of ions. We show that when charges are added in the form of protons to the domains (one proton per domain), the optimized structure is open. No stable water hydrogen bonds hold it together; an opening of 11.0 A appears, measured diagonally between non-neighboring domains as glutamine 119 carbonyl O-O distance. This is comparable to the opening in the MthK potassium channel structure that is generally agreed to be open. The appearance of the opening is in rather good agreement with that found by Perozo and coworkers. In contrast, in the uncharged structure this diagonal distance is 6.5 A, and the water "basket" constricts the uncharged opening still further, with the ice-like structure that couples the K(+) ion to the gating region freezing the entrance to the channel. Comparison with our earlier model for voltage gated channels suggests that a similar mechanism may apply in those channels. PMID- 17336922 TI - Interpretation biases in social anxiety: response generation, response selection, and self-appraisals. AB - Cognitive theories propose that the resolution of ambiguity is related to the maintenance of social anxiety. A sentence completion task was used to examine how individuals high (n=26) and low (n=23) in social anxiety resolve ambiguous social sentences. Individuals were asked to generate as many responses as came to mind for each sentence, and then to endorse the response that best completes the sentence. Total responses, first responses, and endorsed responses were examined separately. Results indicated that high anxious individuals had more negative and anxious responses and fewer positive and neutral responses than low anxious individuals on all sentence completion measures. In contrast, a self-report measure of interpretation bias indicated that more of negative and anxious appraisals were related to social anxiety, while positive and neutral appraisals were not. Results are discussed in terms of a multi-stage processing model of interpretation biases. PMID- 17336923 TI - MD and NMR studies of alpha-bungarotoxin surface accessibility. AB - Protein surface accessibility represents a dimension of structural biology which has not been discussed in details so far, in spite of its fundamental role in controlling the molecular recognition process. In the present report the surface accessibility of alpha-bungarotoxin, a small and well characterized protein, has been investigated by analyzing its interaction with solvent and paramagnetic molecules in an integrated way. The presence of strong hydration sites, identified by a combined analysis of MD simulation and NMR results, seems to prevent the access of Gd(III)DTPA-BMA to the protein surface. On the contrary, the limited hydration of the alpha-bungarotoxin active site favors frequent encounters between the paramagnetic probe and the protein in the latter region. All the data obtained here for alpha-bungarotoxin suggest that shape and stability of the solvation shell control its surface accessibility and, hence, intermolecular interactions in a way which could be common to many other proteins. PMID- 17336924 TI - Mutational analysis of the mitochondrial tRNALeu(UUR) gene in Tunisian patients with mitochondrial diseases. AB - The mitochondrial tRNA(Leu(UUR)) gene (MTTL) is a hot spot for pathogenic mutations that are associated with mitochondrial diseases with various clinical features. Among these mutations, the A3243G mutation was associated with various types of mitochondrial multisystem disorders, such as MIDD, MELAS, MERRF, PEO, hypertrophic cardiomyopathy, and a subtype of Leigh syndrome. We screened 128 Tunisian patients for the A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene. This screening was carried out using PCR-RFLP with the restriction endonuclease ApaI. None of the 128 patients or the 100 controls tested were found to carry the mitochondrial A3243G mutation in the tRNA(Leu(UUR)) gene in homoplasmic or heteroplasmic form. After direct sequencing of the entire mitochondrial tRNA(Leu(UUR)) gene and a part of the mitochondrial NADH dehydrogenase 1, we found neither mutations nor polymorphisms in the MTTL1 gene in the tested patients and controls, and we confirmed the absence of the A3243G mutation in this gene. We also found a T3396C transition in the ND1 gene in one family with NSHL which was absent in the other patients and in 100 controls. Neither polymorphisms nor other mutations were found in the mitochondrial tRNA(Leu(UUR)) gene in the tested patients. PMID- 17336925 TI - Activation of LFA-1 by ionomycin is independent of calpain-mediated talin cleavage. AB - Activation of calpains by calcium flux leading to talin cleavage is thought to be an important process of LFA-1 activation by inside-out signalling. Here, we tested the effects of the calcium ionophore ionomycin and calpain inhibitor calpeptin on LFA-1-mediated adhesion of a T cell hybridoma line, cytotoxic T cells and primary resting T cells. Ionomycin activated LFA-1-mediated adhesion of all three types of T cells, and calpeptin inhibited the effects of ionomycin. However, calpeptin also inhibited activation of LFA-1 by PMA, which did not induce calcium flux. Cleavage of talin was undetectable in ionomycin-treated T cells. Furthermore, treatment with ionomycin and calpeptin induced apoptosis of T cells. Inhibitors of phosphatidyl Inositol-3 kinase inhibited activation of LFA-1 by ionomycin, but not by PMA, whereas the protein kinase C inhibitor inhibited the effects of PMA, but not ionomycin. Thus, activation of LFA-1 by ionomycin is independent of calpain-mediated talin cleavage. PMID- 17336926 TI - Persistent tetrodotoxin-resistant Na+ currents are activated by prostaglandin E2 via cyclic AMP-dependent pathway in C-type nodose neurons of adult rats. AB - It has been documented that nodose neurons express TTX-sensitive (TTX-S) and TTX resistant (TTX-R) Na(+) channels. However, wheteher nodose neurons functionally express persistent TTX-R Na(+) currents has not been reported. The present study first demonstrated persistent TTX-R Na(+) channel activities in 7/19 C-type nodose neurons in the presence of PGE(2) using whole-cell patch. Voltage dependent property showed that persistent TTX-R Na(+) currents were activated at near -60mV and channels were maintained open. The average peak was approximately 300-500pA. The mid-point of activation exhibited a greater shift to a more hyperpolarized potential in the neurons co-expressing TTX-R and persistent TTX-R Na(+) currents than those expressing TTX-R only. This effect of PGE(2) was also mimicked by Forskolin. The fact that persistent TTX-R Na(+) currents were only activated by PGE(2) suggested that the modulatory effects of PGE(2) on persistent TTX-R Na(+) currents are crucial in PGE(2)-mediated neuronal excitability, and may have a great impact on specifically physiological significance. PMID- 17336927 TI - Synip phosphorylation is required for insulin-stimulated Glut4 translocation. AB - Previously we identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS(97)xS(99)) with serine 99 as a unique Akt2, but not Akt1 or for Akt3, substrate phosphorylation site. Although we have previously reported that serine 99 to phenylalanine (S99F-Synip) resulted in a constitutive inhibition of insulin-stimulated Glut4 translocation, a recent report indicated that Synip serine 99 to alanine mutant (S99A-Synip) failed to inhibit insulin-stimulated Glut4 translocation [H. Sano, S. Kane, E. Sano, G.E. Lienhard, Synip phosphorylation does not regulate insulin-stimulated GLUT4 translocation, Biochem. Biophys. Res. Commun. 332 (2005) 880-884]. To address this apparent discrepancy, we have now examined the S99A-Synip mutant and find that this mutant behaves essentially identical to S99F-Synip in that overexpression inhibits insulin-stimulated Glut4 translocation and is incapable of undergoing insulin-stimulated Syntaxin4 dissociation. These data are consistent with Synip serine 99 phosphorylation required for insulin-stimulated Glut4 translocation. PMID- 17336928 TI - A reporter gene assay for screening of PDE4 subtype selective inhibitors. AB - Phosphodiesterase (PDE) constitutes a superfamily of enzymes that catalyze the hydrolysis of cAMP and cGMP into their corresponding monophosphates and play an important role in diverse physiological functions. The present study provides a process for identifying PDE4 subtypes selective inhibitors using a reporter gene assay. Stable recombinant HEK-293 cell lines expressing high levels of PDE4A4B, PDE4B2A, and PDE4D3 subtypes individually were generated. Transient transfection of pCRE-Luc plasmid, harboring luciferase reporter gene under the control of cAMP response element (CRE)-binding sequence, into these stable recombinant cell lines followed by treatment with PDE4 inhibitor, resulted in a dose dependent increase in luciferase activity. This methods provide a novel, simple and sensitive assay for high throughput screening of PDE4 subtype selective inhibitors for treatment of asthma and COPD. PMID- 17336930 TI - Osteopontin stimulates vascular smooth muscle cell migration by inducing FAK phosphorylation and ILK dephosphorylation. AB - Focal adhesion kinase (FAK) and integrin-linked kinase (ILK) are both involved in integrin-mediated cell migration. However, the molecular mechanism, and the relationship between FAK and ILK activity in signaling transduction for the osteopontin (OPN)-induced migration of vascular smooth muscle cells (VSMCs) remain unclear. Here, we show that treating VSMCs with OPN could result in the dissociation of FAK with ILK by inducing phosphorylation of the former and dephosphorylation of the latter. Furthermore, we demonstrate that FAK phosphorylation induced by OPN is coupled with ILK dephosphorylation. We also provide evidence that ILK acts downstream of FAK in the signaling pathways that mediate OPN-induced VSMC migration. These findings suggest that FAK phosphorylation and ILK dephosphorylation play important roles in VSMC migration induced by OPN. PMID- 17336929 TI - Identification of a novel PP2C-type mitochondrial phosphatase. AB - A novel phosphatase has been cloned and partially characterized. It has a mitochondrial leader sequence and its amino acid sequence places it in the PP2C family like two known mitochondrial phosphatases. Western blot analysis of subcellular fractions and confocal microscopy of 3T3L1 preadipocytes expressing the GFP-tagged protein confirm its mitochondrial localization. Western blot analysis indicates that the protein is expressed in several mouse tissues, with highest expression in brain, heart, liver, and kidney. The recombinant protein exhibits Mn(2+)-dependent phosphoserine phosphatase activity against the branched chain alpha-keto acid dehydrogenase complex, suggesting the enzyme may play a role in regulation of branched chain amino acid catabolism. Whether there are other mitochondrial substrates for the enzyme is not known. PMID- 17336931 TI - CNP infusion attenuates cardiac dysfunction and inflammation in myocarditis. AB - Myocarditis is an acute inflammatory disease of the myocardium for which there is currently no specific therapy. We investigated the therapeutic potential of C type natriuretic peptide (CNP) in acute experimental autoimmune myocarditis. One week after injection of porcine myosin into male Lewis rats, CNP (0.05 microg/kg/min) was continuously administered for 2 weeks. CNP infusion significantly increased maximum dP/dt, decreased left ventricular end-diastolic pressure, and improved fractional shortening compared with vehicle administration. In vehicle-treated hearts, severe necrosis and marked infiltration of CD68-positive inflammatory cells were observed. Myocardial and serum levels of monocyte chemoattractant protein-1 were elevated in myocarditis. However, these changes were attenuated by CNP infusion. In addition, treatment with CNP significantly increased myocardial capillary density. Guanylyl cyclase B, a receptor for CNP, was expressed in myocarditic heart, and cyclic guanosine monophosphate was elevated by CNP infusion. In conclusion, CNP infusion attenuated cardiac function in acute myocarditis through anti-inflammatory and angiogenic effects. PMID- 17336932 TI - A novel beta-galactosidase capable of glycosyl transfer from Enterobacter agglomerans B1. AB - A novel transglycosylating beta-galactosidase was purified from Enterobacter agglomerans B1. It was a homodimer of approximately 248 kDa. The optimal pH and temperature for oNPGal hydrolysis were 7.5-8.0 and 37-40 degrees C, respectively. The K(m) values for oNPGal and lactose were 0.06 and 114 mM, respectively. The enzyme produced galacto-oligosaccharides in a 38% yield at the lactose concentration of 12.5% (w/v). When using oNPGal as donor, the enzyme was able to catalyze glycosyl transfer to a series of acceptors, including hexose, pentose, beta- or alpha-disaccharides, hexahydroxy alcohol, cyclitol, and aromatic glycosides. This suggested the enzyme to be a potential synthetic tool for preparing galactose-containing chemicals. The gene encoding this enzyme was cloned by degenerate PCR and TAIL-PCR. It revealed an ORF of 3090 nucleotides encoding a 1029 amino-acid protein, which had been expressed in Escherichia coli. Transferase activities in both recombinant and natural enzymes were similar. PMID- 17336933 TI - GC content variability of eubacteria is governed by the pol III alpha subunit. AB - Eubacterial genomes have highly variable GC content (0.17-0.75) and the primary mechanism of such variability remains unknown. The place to look for is what actually catalyzes the synthesis of DNA, where DNA polymerase III is at the center stage, particularly one of its 10 subunits--the alpha subunit. According to the dimeric combination of alpha subunits, GC contents of eubacterial genomes were partitioned into three groups with distinct GC content variation spectra: dnaE1 (full-spectrum), dnaE2/dnaE1 (high-GC), and polC/dnaE3 (low-GC). Therefore, genomic GC content variability is believed to be governed primarily by the alpha subunit grouping of DNA polymerase III; it is of essence in genome composition analysis to take full account of such a grouping principle. Since horizontal gene transfer is very frequent among bacterial genomes, exceptions of the grouping scheme, a few percents of the total, are readily identifiable and should be excluded from in-depth analyses on nucleotide compositions. PMID- 17336934 TI - Prion inactivation by the Maillard reaction. AB - Since variant Creutzfeldt-Jakob disease (vCJD) has been suspected to be attributable to the infectious agents associated with bovine spongiform encephalopathy (BSE), it is important to prevent the transmission of pathogenic forms of prion protein (PrP(Sc)) through contaminated feeding materials such as meat and bone meal (MBM). Here, we demonstrate that the Maillard reaction employing a formulation of glucose in combination with sodium hydrogen carbonates effectively reduced the infectivity (approximately 5.9-log reduction) of a scrapie-infected hamster brain homogenate. In addition to a bioassay, a protein misfolding cyclic amplification (PMCA) technique, in which PrP(Sc) can be amplified in vitro, was used as a rapid test for assessing PrP(Sc) inactivation. The PMCA analysis also indicated that the PrP(Sc) level in the infected material significantly decreased following the Maillard reaction. Therefore, the Maillard reaction can be employed for the decontamination of large amounts of byproducts such as MBM. PMID- 17336935 TI - Interferon-gamma and NF-kappaB mediate nitric oxide production by mesenchymal stromal cells. AB - Mesenchymal stromal cells (MSCs) have been shown to have an immunosuppressive effect. Previously, we demonstrated that nitric oxide (NO) is one of the immunomodulatory mediators of MSCs. We herein show that primary mouse bone marrow MSCs and three cell lines that mimic MSCs suppress both differentiation and proliferation in Th1 condition, whereas the suppression in Th2 condition is mild. NO production is inversely correlated with T cell proliferation in Th1 and Th2 conditions. NO is highly induced in Th1 and minimally induced in Th2. Moreover, an inhibitor of NO synthase restores both proliferation and interferon-gamma (IFN gamma) production in Th1 condition. Furthermore, an anti-IFN-gamma antibody strongly inhibits NO production and an inhibitor of NF-kappaB reduces the level of induction of inducible NO synthase (iNOS) in MSCs. Taken together, our results suggest that NO plays a significant role in the modification of Th1 and Th2 differentiation by MSCs, and that both IFN-gamma and NF-kappaB are critical for NO production by MSCs. PMID- 17336936 TI - Parallel evaluation of antimicrobial peptides derived from the synthetic PAF26 and the human LL37. AB - The antimicrobial hexapeptide PAF26 was de novo designed towards phytopathogenic fungi of agricultural importance. To analyze its clinical potential, the activity of PAF26 has been determined against several microorganisms of clinical relevance including Staphylococcus, Candida, and several dermatophytes. For comparison purposes, the peptides KR20 and KI26 derived from the human cathelicidin LL37 were selected and fungal pathogens of agronomic relevance were included. PAF26 has similar antimicrobial activity in vitro compared to KR20 despite their different lengths and amino acid compositions. Moreover, neither peptide is lytic to human erythrocytes or keratinocytes. The hybrid peptide PAF26:KR20 showed better antimicrobial properties than the original peptides against most of the pathogens tested. The structural properties of PAF26:KR20 compared to related 26 amino acid peptides support the idea that the increment in toxicity correlates with positive charge and hydrophobicity. However, the degree of peptide helicity was not a predictor of antimicrobial activity. PMID- 17336937 TI - Electroconvulsive seizures stimulate glial proliferation and reduce expression of Sprouty2 within the prefrontal cortex of rats. AB - BACKGROUND: Reductions in cell number are found within the medial prefrontal cortex (PFC) in major depression and bipolar disorder, conditions for which electroconvulsive therapy (ECT) is a highly effective treatment. We investigated whether electroconvulsive seizure (ECS) in rats stimulates cellular proliferation in the PFC immediately and four weeks after the treatments. In parallel, we examined if ECS also alters the expression of Sprouty2 (SPRY2), an inhibitor of cell proliferation. METHODS: Sprague-Dawley rats received 10 days of ECS treatments and bromodeoxyuridine (BrdU) injections. After a four week survival period, we estimated the density and number of BrdU-, proliferating cell nuclear antigen (PCNA)-, and SPRY2-immunoreactive cells in the medial (infralimbic) PFC (ILPFC). We also determined the percentage of BrdU-labeled cells that were immunoreactive for markers specific to oligodendrocytes, astrocytes, endothelial cells and neurons. RESULTS: ECS dramatically enhanced the proliferation of new cells in the infralimbic PFC, and this effect persisted four weeks following the treatments. The percentage of new cells expressing oligodendrocyte precursor cell markers increased slightly following ECS. In contrast, ECS dramatically reduced the number of cells expressing SPRY2. CONCLUSIONS: ECS stimulates long-lasting increases in glial proliferation within the ILPFC. ECS also decreases SPRY2 expression in the same region, an effect that might contribute to increased glial proliferation. PMID- 17336939 TI - Relationship between neuroticism personality trait and serotonin transporter binding. AB - BACKGROUND: Personality trait is thought to be one of the important factors for vulnerability to depression. The relation between serotonin transporter (5-HTT) polymorphism and anxiety-related personality has been investigated in genetic research. In this study, we investigated the relation between in vivo regional 5 HTT binding in the brain and personality inventory measures in normal male volunteers. METHODS: Thirty-one healthy male volunteers underwent positron emission tomography scans with (11)C-labeled 3-amino-4-(2-dimethylaminomethyl phenylsulfanyl) benzonitrile ([(11)C]DASB) to measure 5-HTT and completed revised NEO Personality Inventory. Correlation of [(11)C]DASB binding potentials (BP) with personality inventory measures was calculated using region-of-interest analysis and statistical parametric mapping based on the BP images. RESULTS: Neuroticism was positively correlated with 5-HTT binding in the thalamus (p = .004). No significant correlation was observed in any other brain region. Within the neuroticism dimension, the facet of depression was positively correlated with 5-HTT binding in the thalamus (p = .001). CONCLUSIONS: Subjects with higher thalamic 5-HTT binding are more likely to express higher levels of neuroticism and depressive feeling. Serotonin transporter binding in the thalamus might be a marker of vulnerability to depression. PMID- 17336938 TI - Mu (mu) opioid receptor regulation of ethanol-induced dopamine response in the ventral striatum: evidence of genotype specific sexual dimorphic epistasis. AB - BACKGROUND: Ethanol stimulates the dopaminergic mesoaccumbal pathway, which is thought to play a role in ethanol reinforcement. Mu (mu)-opioid (MOP) receptors modulate accumbal dopamine activity, but it is not clear whether MOP receptors are involved in the mechanism of ethanol-stimulated accumbal dopamine release. METHODS: We investigated the role that MOP receptors play in ethanol (2.0 g/kg) stimulated accumbal dopamine release by using MOP receptor knockout mice (C57BL/6J-129SvEv and congenic C57BL/6J genotypes) along with blockade of MOP receptors with a mu1 selective antagonist (naloxonazine). RESULTS: Both gene deletion and pharmacological antagonism of the MOP receptor decreased ethanol stimulated accumbal dopamine release compared with controls with female mice showing a larger effect in the C57BL/6J-129SvEv genotype. However, both male and female mice showed reduced ethanol-stimulated dopamine release in the congenic MOP receptor knockout mice (C57BL/6J). No differences in the time course of dialysate ethanol concentration were found in any of the experiments. CONCLUSIONS: The data demonstrate the existence of a novel interaction between genotype and sex in the regulation of ethanol-stimulated mesolimbic dopamine release by the MOP receptor. This implies that a more complete understanding of the epistatic influences on the MOP receptor and mesolimbic dopamine function may provide more effective pharmacotherapeutic interventions in the treatment of alcoholism. PMID- 17336940 TI - Effects of metyrapone on hypothalamic-pituitary-adrenal axis and sleep in women with post-traumatic stress disorder. AB - BACKGROUND: Metyrapone blocks cortisol synthesis which results in removal of negative feedback, a stimulation of hypothalamic corticotropin releasing factor (CRF) and a reduction in delta sleep. We previously reported a diminished delta sleep and hypothalamic-pituitary-adrenal (HPA) response to metyrapone in men with post-traumatic stress disorder (PTSD). In this study, we aimed to extend these findings to women. METHODS: Three nights of polysomnography were obtained in 17 women with PTSD and 16 controls. On day 3, metyrapone was administered throughout the day up until bedtime. Plasma adrenocorticotropic hormone (ACTH), cortisol, and 11-deoxycortisol were obtained the morning following sleep recordings the day before and after metyrapone administration. RESULTS: There were no significant between-group differences in hormone concentration and delta sleep at baseline. Relative to controls, women with PTSD had decreased ACTH and delta sleep responses to metyrapone. Decline in delta sleep was associated with the magnitude of increase in ACTH across groups. CONCLUSIONS: Similar to our previous findings in men, the ACTH and sleep electroencephalogram response to metyrapone is attenuated in women with PTSD. These results are consistent with a model of downregulation of CRF receptors in an environment of chronically increased CRF activity or with enhanced negative feedback regulation in PTSD. PMID- 17336941 TI - Family history of alcoholism influences naltrexone-induced reduction in alcohol drinking. AB - BACKGROUND: The purpose of this study was to examine the interactive effects of family history of alcoholism (FH+, FH-) and naltrexone dose (0, 50, 100 mg/day) on alcohol drinking. METHODS: Ninety-two, non-treatment-seeking alcohol-dependent participants received naltrexone daily for 6 days. On the 6th day, they participated in a laboratory paradigm involving exposure to a priming dose of alcohol followed by a 2-hour drinking period in which they made choices between consuming alcoholic drinks and receiving money. RESULTS: Total number of drinks consumed during the drinking period was significantly decreased by the 100-mg dose of naltrexone in FH+ drinkers. Secondary analyses in male drinkers (n = 70) indicated that 100 mg of naltrexone significantly decreased drinking in FH+ participants and increased drinking in FH- drinkers. CONCLUSIONS: These results suggest that family history of alcoholism might be a significant clinical predictor of response to naltrexone and that FH+ men are more likely to benefit from naltrexone therapy for alcohol drinking. PMID- 17336942 TI - Regulation of serotonin-1A receptor function in inducible brain-derived neurotrophic factor knockout mice after administration of corticosterone. AB - BACKGROUND: We examined the effects of a forebrain-specific reduction in brain derived neurotrophic factor (BDNF) on the regulation of serotonin-1A (5-HT1A) receptor function in serotonergic cell body areas as well as in limbic and cortical structures of mice chronically treated with corticosterone. METHODS: 5 HT1A receptor function, at the level of receptor-G protein interaction, was assessed with quantitative autoradiography of [35S]GTPgammaS binding stimulated by the 5-HT1A receptor agonist 8-OH-DPAT. 5-HT1A receptor number was assessed by measuring the binding of the antagonist radioligand [3H] WAY100635. RESULTS: We observed a significant attenuation of 5-HT1A receptor function, in the absence of a change in receptor number, in the dorsal hippocampus of BDNF knockout versus control mice. There was no difference between control and BDNF knockout mice in 5 HT1A receptor number or function in the dorsal or median raphe nuclei or medial prefrontal cortex or anterior cingulate cortex. Corticosterone treatment of control mice decreased 5-HT1A receptor function in the dorsal and median raphe but not in hippocampus or frontal cortical areas. The regulation of 5HT1A receptor number or function in the dorsal and median raphe by corticosterone was lost in BDNF knockout mice. CONCLUSIONS: Attenuation of BDNF expression in forebrain regions produces differential effects on distinct 5-HT1A receptor populations and on the regulation of these receptor populations by corticosterone. PMID- 17336943 TI - The association of major depression, conduct disorder, and maternal overcontrol with a failure to show a cortisol buffered response in 4-month-old infants of teenage mothers. AB - BACKGROUND: Adolescent pregnancy can be associated with major depression (MD) and conduct disorder (CD). Some infants of adolescent mothers are prenatally exposed to these factors, which may result in heightened risk for perturbations of their stress systems. Between 2 and 4 months, a normal shift occurs in the adrenocortical system in which we observe a marked decrease in infant cortisol response when facing mild stressors. This study aimed to explore whether MD (lifetime, during pregnancy, postpartum), CD, and maternal overcontrol are associated with increased cortisol reactivity in 4-month-old infants of teenage mothers. METHODS: Using arm restraint as a stressor, morning salivary cortisol was taken prestressor and poststressor in 212 infants during a laboratory visit. Major depression and CD were measured with the computerized National Institute of Mental Health Diagnostic Interview Schedule (NIMH-DIS), postpartum depressive mood was measured with the Edinburgh Postnatal Depression Scale, and overcontrol was observed with the CARE-Index. RESULTS: Independent of the predictors, there was a dampened cortisol response. Infants of mothers with lifetime MD and of average to highly overcontrolling mothers showed increased cortisol reactivity. Conduct disorder and cortisol levels were not associated. CONCLUSIONS: Future studies should detect whether the absence of a dampened cortisol response in infants whose mothers have lifetime MD or display overcontrolling parenting is stable over time. PMID- 17336944 TI - Resting state cortical connectivity reflected in EEG coherence in individuals with autism. AB - BACKGROUND: Theoretical conceptions of autism spectrum disorder (ASD) and experimental studies of cerebral blood flow suggest abnormalities in connections among distributed neural systems in ASD. METHODS: Functional connectivity was assessed with electroencephalographic coherence between pairs of electrodes in a high-density electrode array in narrow frequency bands among 18 adults with ASD and 18 control adults in an eyes closed resting state. RESULTS: In the theta (3-6 Hz) frequency range, locally elevated coherence was evident for the ASD group, especially within left hemisphere frontal and temporal regions. In the lower alpha range (8-10 Hz), globally reduced coherence was evident for the ASD group within frontal regions and between frontal and all other scalp regions. The ASD group exhibited significantly greater relative power between 3 and 6 Hz and 13-17 Hz and significantly less relative power between 9 and 10 Hz. CONCLUSIONS: Robust patterns of over- and under-connectivity are apparent at distinct spatial and temporal scales in ASD subjects in the eyes closed resting state. PMID- 17336945 TI - A functional magnetic resonance imaging study of amygdala responses to human faces in aging and mild Alzheimer's disease. AB - BACKGROUND: Neuropsychiatric symptoms are very common even in mild stages of Alzheimer's disease (AD). The amygdala exhibits very early pathology in AD, but amygdala function in mild AD has received relatively little attention. The current study investigates functional alterations in the amygdala in aging and mild AD, and their relationships with neuropsychiatric symptoms. METHODS: Functional magnetic resonance imaging (fMRI) was used to examine and compare amygdala responses in 12 young and elderly controls and in 12 mild AD patients during viewing of neutral and emotional human facial expressions. RESULTS: Amygdala responses in the young and elderly did not significantly differ from each other. However, the AD group had significantly greater amygdala responses to both neutral and emotional faces relative to elderly controls. This group effect was maintained when amygdala volume, sex and age were included as covariates in the analysis. Furthermore, amygdala activity correlated with the severity of irritability and agitation symptoms in AD. CONCLUSIONS: The amygdala in patients with mild AD is excessively responsive to human faces relative to elderly controls. These amygdala functional alterations may represent a physiologic marker for certain neuropsychiatric manifestations of AD. PMID- 17336946 TI - Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level. AB - BACKGROUND: Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia. METHODS: We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1, NRG1, DAOA/G32, and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated. RESULTS: The DTNBP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. The DTNBP1 haplotype load had borderline associations with nonverbal IQ, paranoid schizotypy, and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected. CONCLUSIONS: The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level. PMID- 17336947 TI - Distinct neural correlates underlying two- and three-dimensional mental rotations using three-dimensional objects. AB - Two strategies-motor and visual-are considered to be used for performing mental rotation. The former involves the functions of the motor-related areas of the brain, whereas the latter does not. It is known that subjects' experiences influence strategy selection during the mental rotation of three-dimensional (3D) shapes. However, it remains questionable as to whether the attributes of 3D objects enhance the motor-related activities. In this regard, using functional magnetic resonance imaging, we compared the brain activities during two types of mental rotations-two-dimensional (2D) and 3D rotations-using 3D objects. 2D rotation using 3D objects requires rotation in a screen plain, whereas 3D rotation requires in-depth rotation. Only 3D rotation implicitly requires subjects to construct and manipulate 3D images with visualizations of the hidden parts; this plays an important role in visuo-motor tasks such as preshaping. As a result, a wide area of the right superior parietal lobule (SPL) was activated in relation to a 2D rotation angle. Conversely, a wide area of the right dorsal premotor cortex (PMd) was activated in relation to a 3D rotation angle. The right PMd activity is related to visualization of the hidden parts of visual stimuli, which is required only for 3D rotation. This implies that task difficulty enhanced by rotation dimensionality is a major factor related to the selection of motor strategy. In addition, it implies that the right SPL and the right PMd play important roles in rotation imagery without visualization and in constructing and manipulating 3D images, respectively. PMID- 17336948 TI - Fungal cell wall polysaccharides isolated from Discula destructiva spp. AB - The alkali-extractable water-soluble polysaccharides F1SS isolated from the cell wall of four species of Discula destructiva have been studied by methylation analysis and NMR spectroscopy, and their idealized structures established as [structure: see text] where n approximately 2 for strains CBS 109771 and CBS 133.91, n approximately 1 for CBS 132.91, and it has an intermediate value in strain CBS 130.91. The mannan core was obtained by mild hydrolysis of the F1SS polysaccharide and its structure consisted of a skeleton of alpha-(1-->6) mannopyranan, with around one out of eleven residues substituted at C-2 by short chains (one to six units) of 2-substituted mannopyranoses. PMID- 17336949 TI - Acyl chloride/DABCO-promoted acetal migration of 1,2:4,5-di-O-isopropylidene-D fructopyranose. AB - An unprecedented acetal migration was observed when 1,2:4,5-di-O-isopropylidene-D fructose was treated with various acyl chlorides and 1,4-diaza bicyclo[2.2.2]octane (DABCO). 2,3:4,5-Di-O-isopropylidene-D-fructose derivatives were isolated as the only product in high to quantitative yields. The acylium cations generated in situ were speculated as the electrophilic species to initiate the migration process. PMID- 17336950 TI - Stimulation of multiple cytokine production in mice by alginate oligosaccharides following intraperitoneal administration. AB - We previously reported that alginate oligomers, prepared by specific enzymatic digestion of alginate polymer, induced cytokine secretion from mouse macrophage cell line RAW264.7. In the present study, we examined the cytokine levels in the mouse serum after intraperitoneal (ip) administration of a mixture of alginate oligomers. After ip injection of 700 mg/kg of oligomers, the serum level of G-CSF increased promptly and reached the maximum level after 2 h and this high level was sustained until 6 h, and then gradually decreased, whereas injection of 700 mg/kg of alginate polymer had no effect. The effect of alginate oligomer mixture was dose-dependent, and 70 mg/kg was sufficient to attain the maximum serum level of G-CSF. A Bio-Plex bead assay that can detect 23 cytokines at the same time revealed that ip administration of alginate oligomer mixture induced an increase in 20 cytokines in the serum at different levels and with different kinetics depending on the cytokine. Among the cytokines detected the level of G-CSF was the highest. The levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, keratinocyte-derived chemokine (KC), IL-12 (p40), and regulated upon activation normal T cell expressed and secreted (RANTES) were also relatively high and exceeded 5000 pg/mL serum at the peak point. PMID- 17336951 TI - Impact of phenolic compounds on hydrothermal oxidation of cellulose. AB - The effect of phenolic compounds on hydrothermal oxidation of cellulose was studied using a batch reactor at 300 degrees C with H(2)O(2) as oxidant. Intermediate products, as well as the yields of acetic acid produced in the oxidation of cellulose, phenolic compounds, and cellulose-phenolic compound mixtures were examined. Phenolic compounds used were phenol, 1,4-benzenediol, 2 methoxy-4-methylphenol, and 2,6-di-tert-butyl-4-methylphenol. In the case of oxidation of cellulose-phenolic compound mixtures, (1) formic acid, a basic oxidation product from carbohydrates, decreased considerably, (2) 5-hydroxymethyl 2-furaldehyde and 2-furaldehyde, acid-catalyzed dehydration products from carbohydrates, appeared, and (3) the yield of acetic acid increased compared to that in the oxidation of cellulose. From these results, phenolic compounds seem to inhibit the oxidation of cellulose under hydrothermal conditions. The inhibition of the oxidation of cellulose by phenolic compounds seems to be related closer to the stability of phenolic compounds under oxidation conditions rather than the ease to remove phenolic hydrogen on the OH group. PMID- 17336952 TI - Rhythm control for atrial fibrillation: non-channel antiarrhythmic drugs are en vogue. PMID- 17336953 TI - Calcium waves driven by "sensitization" wave-fronts. AB - OBJECTIVE: Cellular Ca(2+) waves are understood as reaction-diffusion systems sustained by Ca(2+)-induced Ca(2+) release (CICR) from Ca(2+) stores. Given the recently discovered sensitization of Ca(2+) release channels (ryanodine receptors; RyRs) of the sarcoplasmic reticulum (SR) by luminal SR Ca(2+), waves could also be driven by RyR sensitization, mediated by SR overloading via Ca(2+) pump (SERCA), acting in tandem with CICR. METHODS: Confocal imaging of the Ca(2+) indicator fluo-3 was combined with UV-flash photolysis of caged compounds and the whole-cell configuration of the patch clamp technique to carry out these experiments in isolated guinea pig ventricular cardiomyocytes. RESULTS: Upon sudden slowing of the SERCA in cardiomyocytes with a photoreleased inhibitor, waves indeed decelerated immediately. No secondary changes of Ca(2+) signaling or SR Ca(2+) content due to SERCA inhibition were observed in the short time-frame of these experiments. CONCLUSIONS: Our findings are consistent with Ca(2+) loading resulting in a zone of RyR 'sensitization' traveling within the SR, but inconsistent with CICR as the predominant mechanism driving the Ca(2+) waves. This alternative mode of RyR activation is essential to fully conceptualize cardiac arrhythmias triggered by spontaneous Ca(2+) release. PMID- 17336954 TI - International Symposium on the Evaluation of Butadiene and Chloroprene Health Risks. AB - These proceedings represent nearly all the platform and poster presentations given during the International Symposium on Evaluation of Butadiene and Chloroprene Health Risks, held in Charleston, South Carolina, USA, on September 20-22, 2005. The Symposium was attended by 78 participants representing private industry (37), academia (21), government (11), not-for-profit organizations (5), and consulting (4). The program followed the format of previous symposia on butadiene, chloroprene, and isoprene in London UK (2000) and butadiene and isoprene in Blaine, Washington USA (1995). This format enabled the exchange of significant new scientific results and discussion of future research needs. Isoprene was not evaluated during the 2005 Symposium because of lack of new data. For background information, the reader is referred to the proceedings of the London 2000 meeting for a thorough historical perspective and overview of scientific and regulatory issues concerning butadiene, chloroprene, and isoprene [Chem.-Biol. Interact. (2001) 135-136:1-7]. The Symposium consisted of seven sessions: (1) Introduction and Opening Remarks, (2) Butadiene/styrene-butadiene rubber (SBR)--Process Overview, Exposure and Health Effects/Human Studies; (3) Chloroprene--Process Overview, Exposure and Health Effects/Human Studies; (4) Mode of Action/Key Events; (5) Risk Assessment; (6) Poster Presentations; and (7) Panel Discussion and Future Directions. The Symposium concluded with a discussion by all participants of issues that arose throughout the course of the Symposium. The Proceedings of the Symposium published in this Special Issue are organized according to the Sessions outlined above. The purpose of this foreword is to summarize the presentations and their key findings and recommend future research directions for each chemical. PMID- 17336955 TI - Ubiquinol-10/lipids ratios in consecutive patients with different angiographic findings. AB - OBJECTIVE: Information concerning un-supplemented plasma concentrations of ubiquinol-10 in coronary artery disease patients is still controversial. The aim of this study is to determine the levels of plasma ubiquinol-10 and ratios of ubiquinol-10 to plasma lipids in consecutive patients with different angiographic findings. SUBJECTS AND METHODS: Thirty-six consecutive patients who underwent coronary angiography were split in two groups with different atherosclerotic changes. These patients were un-supplemented with antioxidants and were not treated by lipid-lowering medication. We have measured a plasma level of ubiquinol-10 using high-performance liquid chromatography with coulometric detection. Conventional plasma lipids, markers of oxidative stress and other widely accepted risk factors of atherosclerosis have been determined too. RESULTS: Plasma ubiquinol-10 to low-density lipoprotein cholesterol (LDL-C) ratios in patients with different angiographic findings have been found as 180+/ 69 and 132+/-43, respectively (p=0.020). The ubiquinol-10/LDL-C ratio was significantly lower in angiographically positive patients. There were also significant differences in ubiquinol-10 per total cholesterol (109+/-47 and 80+/ 26, respectively; p=0.031), per triglycerides (426+/-191 and 237+/-86, respectively; p=0.002) and per the sum of triglycerides and total cholesterol (86+/-35 and 61+/-20, respectively; p=0.013). CONCLUSIONS: There have not been found any significant differences between levels of widely accepted risk factors for genesis and progress of atherosclerotic changes in these two groups of patients. Only the level of triglycerides and the total cholesterol minus high density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were significantly higher in patients with stenosis. This ratio correlated with the ubiquinol-10/LDL-C ratio, which was significantly lower in patients with stenosis. Our results indicate that the ratio of ubiquinol-10/LDL-C is likely to be a risk factor for atherogenesis. PMID- 17336956 TI - On the universality of language comprehension strategies: evidence from Turkish. AB - A fundamental question in psycholinguistic research concerns the universality of comprehension strategies. We investigated this issue by examining the so-called "subject preference" in Turkish, a language which allows for a natural (unmarked) object reading of an initial ambiguous argument. Using event-related brain potentials (ERPs), we observed increased processing difficulty in the form of a broadly distributed positivity when an initial ambiguous argument was disambiguated towards an object reading. This effect was independent of the animacy (i.e. semantic subject prototypicality) of the ambiguous argument. Our results therefore speak in favour of a universal tendency to interpret the first argument encountered as the "subject" of the clause, even in languages providing no obvious structural motivation for such a strategy. However, we argue that the underlying explanation for this preference must be modified in accordance with cross-linguistic considerations. PMID- 17336957 TI - 3D statistical models for tooth surface reconstruction. AB - This paper presents a method to reconstruct the 3D surface of a tooth given partial information about its shape. A statistical model comprising a mean shape and a series of deformation modes is obtained offline using a set of specimens. During reconstruction, rigid registration is performed to align the mean shape with the target. The mean shape is then deformed to approximate the target by minimizing the sum of squared distances between the two surfaces according to the deformation modes. The method is shown to be efficient for the recovery of tooth shape given crown information. PMID- 17336959 TI - Monensin causes transient calcium ion influx into mouse splenic lymphocytes in a sodium ion-independent fashion. AB - Monensin, a Na(+) ionophore, can increase cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in many cell types, but no studies have investigated the mechanism underlying a monensin-induced increase in [Ca(2+)](i) in immune cells. In view of this, we investigated the effect of monensin on [Ca(2+)](i) and cytosolic free Na(+) concentration ([Na(+)](i)) in mouse splenic lymphocytes using a fluorescence Ca(2+) indicator, fura-2, and a fluorescence Na(+) indicator, sodium binding benzofuran isophthalate (SBFI), respectively. Monensin (1-100 microM) caused transient and sustained increases in [Ca(2+)](i) and [Na(+)](i), respectively, in a concentration-dependent manner. The monensin-induced increase in [Ca(2+)](i) was abolished by the omission of extracellular Ca(2+) or 1-[beta [3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride (SKF 96365, 100-150 microM), and was largely inhibited by Ni(2+) (2-5 mM). The omission of extracellular Na(+) failed to inhibit the monensin-induced increases in [Ca(2+)](i). Furthermore, tetrodotoxin (1-10 microM), 5-(N,N-dimethyl) amiloride (DMA, 10-20 microM), 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5 ethoxyaniline (SEA0400, 3-10 microM), verapamil (10-200 microM), nifedipine (10 200 microM), omega-agatoxin IVA (0.2-10 microM), omega-conotoxin GVIA (1-10 microM), omega-conotoxin MVIIC (0.5-10 microM), and nordihydroguaiaretic acid (NDGA, 1-10 microM) had no effect on the increases in [Ca(2+)](i). Monensin induced Mn(2+) influx into splenic lymphocytes. The Mn(2+) influx was completely inhibited by SKF-96365. These results suggest that monensin transiently increases [Ca(2+)](i) in mouse splenic lymphocytes by stimulating Ca(2+) entry via non selective cation channels in a Na(+)-independent manner. PMID- 17336960 TI - An in vitro mouse model for retinal ganglion cell replacement therapy using eye like structures differentiated from ES cells. AB - The aim of this study was to investigate the developmental potential of embryonic stem (ES) cell-derived eye-like structures as a replacement cell therapy model for retinas with N-methyl-d-aspartate (NMDA)-induced damage. For this purpose mouse ES cells were induced to differentiate into eye-like structures in vitro for 10 days and co-cultured with adult mouse retina treated with or without NMDA treatment. NMDA induces excitotoxic neuronal cell death in the inner neural retina, specifically within the ganglion cell layer. After 10 days of co-culture, the specimens were fixed, embedded in paraffin wax and analyzed by immunohistochemistry. Transplanted eye-like structures differentiate into Tuj1 positive neurons when co-cultured with an adult mouse retina and the cells then migrate into the ganglion cell layer. When co-cultured with an NMDA-treated retina, most of the cells migrating into the ganglion cell layer express the ganglion cell-specific markers Hu and Brn3b. Murine ES cell-derived eye-like structures contain cell populations that can differentiate into ganglion-like cells in the host ganglion cell layer in vitro. Moreover, their contribution to the ganglion cell layer was more prominent when ganglion cell specific damage was induced by NMDA administration. These findings suggest that cells prepared from the eye-like structures generated from ES cells may be useful for cell replacement therapy and may also serve as a model system for such therapies. PMID- 17336958 TI - The axon guidance gene lola is required for programmed cell death in the Drosophila ovary. AB - longitudinals-lacking (lola) was identified in Drosophila as a gene encoding several alternatively spliced transcription factors involved in axon guidance. Here we report that lola also plays a critical role in programmed cell death in the ovary. lola mutant germline clones show a high percentage of egg chambers with nurse cell nuclei persisting past stage 13, indicating a block in developmental nurse cell death. Mutants also show a disruption in the induced programmed cell death that occurs during mid-oogenesis in response to starvation. Further characterization revealed that lola germline clones exhibit abnormal nuclear organization which becomes increasingly severe with age. Chromatin appears diffuse and fails to condense properly or undergo DNA fragmentation in dying nurse cells. Masses of nuclear material accumulate in the ovaries of older flies containing lola germline clones. We propose that lola is necessary for complete chromatin condensation which occurs during programmed cell death in the ovary. Alleles differed in the strength of their phenotypes but interestingly, the severity of their ovarian phenotypes was independent of the strength of their neuronal phenotypes, suggesting a differential requirement for individual lola isoforms in the ovary and nervous system. PMID- 17336961 TI - Frequency-dependent distribution of local field potential activity within the subthalamic nucleus in Parkinson's disease. AB - Enhanced oscillatory local field potential (LFP) activities over a broad frequency range (5-30 Hz) have been consistently reported from the basal ganglia in patients with Parkinson's disease (PD) and in animal models of this disease. Here we test the hypothesis that these activities may have different functional connotations according to their frequency, by seeking a relatively differentiated distribution within the different functional territories of the subthalamic nucleus (STN). To this end we made intra-operative microelectrode recordings of LFP activities within the STN of 8 PD patients undergoing functional neurosurgery. A significantly larger beta (13-30 Hz) power was found in the dorsolateral part of STN, which is related to motor cortical areas, compared to the ventral (associative/limbic) part of STN. This specific topography was not observed for low frequency activity (5-12 Hz). Our data suggest that the relative distribution of oscillatory activity within the STN of patients with PD may differ according to frequency and confirm previously reported findings that beta activity may provide a functional marker for the 'motor' STN in functional neurosurgery. PMID- 17336962 TI - Estrogen receptor beta gene +1730 G/A polymorphism in women with endometriosis. AB - OBJECTIVE: To investigate whether the +1730 G/A polymorphism of the estrogen receptor beta (ER-beta) gene is associated with the risk of endometriosis in a Korean population. DESIGN: Case-control study. SETTING: University Department of Obstetrics and Gynecology. PATIENT(S): Women with (n = 239) or without (n = 287) endometriosis. INTERVENTION(S): The +1730 G/A polymorphism of 3'-UTR of exon 8 in the ER-beta gene was assessed by polymerase chain reaction-restriction fragment length polymorphism analysis utilizing digestion with AluI restriction enzyme. MAIN OUTCOME MEASURE(S): Genotype distribution and allele frequency of the +1730 G/A polymorphism in the ER-beta gene. RESULTS: The genotype distribution of the +1730 G/A polymorphism in the ER-beta gene was not different between the endometriosis patients and the controls (G/G of 74.9% vs. 72.5%, G/A of 25.1% vs. 26.1%, and A/A of 0.0% vs. 1.4%, respectively). There was also no difference in the G and A allele frequencies between the two groups (87.4% vs. 85.5%, and 12.6% vs. 14.5%, respectively). Even when the endometriosis cases were subdivided into American Society for Reproductive Medicine stage I-II, III, IV, and III-IV, no differences were found at all in the genotype distribution or allele frequencies between the two groups. CONCLUSION(S): Our results suggest that the +1730 G/A polymorphism of the ER-beta gene may not be associated with the risk of endometriosis in the Korean population, which was not the case in the Japanese population. PMID- 17336963 TI - Repeat vasectomy reversal yields high success rates. AB - We retrospectively reviewed our experiences with repeat vasectomy reversal and report the patency and natural pregnancy rates. Our data demonstrate that repeat vasectomy reversal is a valid option in patients with a failed initial reversal, although the suitability of repeat reversal should be based on the obstructive interval, the original reversal, the experience of the reversal surgeon, and any female factors, as well as the couple's wishes. PMID- 17336964 TI - The effect of raloxifene in association with vitamin D on vaginal maturation index and urogenital symptoms in postmenopausal osteoporotic women. AB - In elderly women with osteoporosis, raloxifene treatment with vitamin D supplementation improves vaginal maturation index and vaginal pH. PMID- 17336965 TI - Ovarian endometrioma vascularization in women with pelvic pain. AB - OBJECTIVE: To assess whether a correlation exists between angiogenesis in ovarian endometrioma with the presence of pelvic pain. DESIGN: Prospective study. SETTING: Tertiary-care university hospital. PATIENT(S): Sixty-five patients (mean age, 33.3 years; range, 20-49 years) were diagnosed as having suspected cystic ovarian endometriosis, and were scheduled for surgery. Patients were classified into two groups according to clinical complaints: group A, asymptomatic patients or patients presenting mild dysmenorrhea; and group B, severe dysmenorrhea and/or chronic pelvic pain and/or dyspareunia. INTERVENTION(S): Transvaginal power Doppler ultrasonography and immunohistochemical staining for CD-34 in histological specimens. MAIN OUTCOME MEASURE(S): The amount of blood flow, lowest pulsatility and resistance indexes, and microvessel density (MVD). RESULT(S): Five patients were excluded after surgery because no ovarian endometriosis was found in histological analysis. Thirty women were included in each group. Ovarian endometriomas were more frequently vascularized in group B (87%) than in group A (60%). The lowest pulsatility and resistance indexes were significantly lower, and MVD was significantly higher, in group B compared with group A. There was a correlation between the degree of vascularization detected by power-Doppler ultrasound and MVD. CONCLUSION(S): We conclude that vascularization of ovarian endometriomas evaluated by transvaginal color Doppler and MVD is higher in patients who present with pelvic pain than in asymptomatic patients. This could be an indicator of the activity of endometriosis. PMID- 17336966 TI - Bladder endometriosis: getting closer and closer to the unifying metastatic hypothesis. AB - OBJECTIVE: It has been hypothesized that bladder endometriotic nodules are an independent form of endometriosis that should be considered a distinct clinical entity. If this is true, the frequency of nonvesical endometriotic lesions in affected patients should be similar to the prevalence of the disease in the general population (about 10%). The aim of the study was to evaluate the presence of other forms of endometriosis in patients with bladder endometriotic nodules. DESIGN: Case series. SETTING: Two gynecologic surgical units. PATIENT(S): Fifty eight women with large bladder endometriotic nodules. INTERVENTION(S): To evaluate the concomitant presence of other forms of endometriosis. MAIN OUTCOME MEASURE(S): Presence of superficial peritoneal implants, ovarian endometriomas, adhesions, and extravesical deep peritoneal endometriosis. RESULT(S): The presence of superficial peritoneal implants, ovarian endometriomas, adhesions, and extravesical deep peritoneal endometriosis was observed in 58.6% (95% confidence interval [CI]: 45.2-71.2), 44.8% (95% CI: 32.2-58.2), 81.0% (95% CI: 68.4-89.6), and 27.6% (95% CI: 16.7-40.8) of cases, respectively. The presence of at least one of them was documented in 87.9% of cases (95% CI: 76.7-94.3). CONCLUSION(S): Endometriotic nodules of the bladder are frequently associated with other forms of pelvic endometriosis. This result does not support the vision that bladder endometriotic nodules should be considered an independent form of the disease. PMID- 17336967 TI - Effect of depomedroxyprogesterone acetate on coagulation parameter: a pilot study. AB - OBJECTIVE: Recent studies have shown changes in coagulation factors, suggesting an increased risk of thrombotic events, in women on progestin-containing contraceptives. To investigate this, we studied the effects of injectable depomedroxyprogesterone acetate (DMPA), given as a contraceptive, on coagulation and inflammation markers. DESIGN: Prospective nonrandomized study. SETTING: Department of Obstetrics and Gynecology, University of Vermont College of Medicine. PATIENT(S): In this substudy of subjects undergoing a phase III trial comparing IM and SC DMPA, 14 healthy reproductive-age women were randomly assigned to receive either IM or SC DMPA every 3 months during a pharmaceutical trial. INTERVENTION(S): All subjects had blood samples obtained at baseline and 6 and 12 months. MAIN OUTCOME MEASURE(S): D-Dimer, C-reactive protein (CRP), antithrombin (AT), factor VIIIc, activated partial thromboplastin time (aPTT), and aPTT plus activated protein C (APC) were analyzed on all samples. RESULT(S): D-Dimer concentration was significantly decreased at 6 and 12 months with injectable DMPA compared t degrees o baseline. There was also a modest decrease in aPTT. The CRP, AT, factor VIIIc, and aPTT + APC were not significantly altered by the use of DMPA. CONCLUSION(S): In this preliminary study the decline in D dimer represents a potentially beneficial change in coagulation function following the use of DMPA given SC or IM. A slight decrease in aPTT may reflect a prothrombotic tendency with this contraceptive, but in contrast with previous studies examining the effect of oral contraceptive this injectable progestin contraceptive did not demonstrate the adverse effect on markers for thrombosis risk. PMID- 17336968 TI - Leukocytospermia: relationship to sperm deoxyribonucleic acid integrity in patients evaluated for male factor infertility. AB - The purpose of our study was to analyze the relationship of leukocytospermia to sperm DNA damage as assessed by the DNA integrity assay. Results indicate that leukocytospermia has a significant negative effect on the standard semen parameters of concentration, motility, and morphology but at most a very weak effect on DNA integrity as measured by the DNA fragmentation assay. PMID- 17336969 TI - Expression of various CDC25B isoforms in human spermatozoa. AB - OBJECTIVE: To explore the role of CDC25B protein in postmeiotic germ cells. DESIGN: In vitro experiment. SETTING: University-based reproductive genetics laboratory. PATIENT(S): Fertile and infertile volunteers. INTERVENTION(S): Reverse transcription-polymerase chain reaction (RT-PCR), real-time RT-PCR, and immunostaining for CDC25B. MAIN OUTCOME MEASURE: Expression profiling of CDC25B in human spermatozoa. RESULT(S): Four splicing variants (CDC25B1, B2, B3, and B4) are expressed in human spermatozoa. Immunofluorescence staining showed strong homogeneous staining in the midpiece of spermatozoa, and weak staining in the principal piece and cytosol of the head. The messenger RNA (mRNA) transcript level of CDC25B was increased in sperm samples of men with asthenospermia. CONCLUSION(S): The expression of CDC25B in different cellular compartments of human spermatozoa suggests that there are diverse noncell-cycle-related functions of CDC25B in terminally differentiated human germ cells. PMID- 17336970 TI - Prospective, randomized trial of metformin and vitamins for the reduction of plasma homocysteine in insulin-resistant polycystic ovary syndrome. AB - One hundred and two women with insulin-resistant polycystic ovary syndrome were randomized to treatment with a vitamin B preparation, metformin, or both, in conjunction with standard infertility treatment. Plasma homocysteine levels were significantly reduced by both B vitamins and metformin, but to a greater degree by B vitamins, and higher pregnancy rates were associated with vitamin B treatment. PMID- 17336971 TI - In vitro maturation of oocytes collected from unstimulated ovaries for oocyte donation. AB - OBJECTIVE: To assess the role of immature oocyte collection from unstimulated ovaries as a potential source of oocyte donation. DESIGN: Prospective cohort study. SETTING: A tertiary, university-based, in vitro fertilization center. PATIENT(S): Twelve oocyte donors with ultrasound-only polycystic ovaries or polycystic ovary syndrome matched with 12 oocyte recipients. INTERVENTION(S): Immature oocyte collection without any ovarian stimulation. In vitro maturation of the oocytes. Embryo transfer of the embryos. MAIN OUTCOME MEASURE(S): Immature oocyte collection, maturation, fertilization, and cleavage rates. Implantation, pregnancy, and live birth rates. RESULT(S): A mean of 12.8 +/- 5.1 Germinal vesicle oocytes were aspirated per collection. The in vitro maturation rate was 68.3% +/- 18.4% with a mean of 8.7 +/- 3.6 mature oocytes per collection. The mean fertilization rate was 73.3% +/- 19.4%. Two to five embryos (median four) were transferred. Six recipients conceived, giving a 50% clinical pregnancy rate per cycle. The mean implantation rate per embryo was 18.2%. The live birth rate per cycle started was 30%. CONCLUSION(S): Collecting immature oocytes from unstimulated ovaries for the purpose of oocyte donation is a simple procedure that totally avoids ovarian stimulation. With appropriate selection of women with ultrasound-only polycystic ovaries or women with the polycystic ovary syndrome, the pregnancy rates of the recipients are comparable with those achieved through conventional IVF oocyte donor cycles. PMID- 17336972 TI - Postmenopausal hypoestrogenism increases vasoconstrictor neuropeptides and decreases vasodilator neuropeptides content in arterial-wall autonomic terminations. AB - OBJECTIVE: To investigate the effects of postmenopausal hypoestrogenism on the content of autonomic vasoconstrictor (neuropeptide Y) and vasodilator neuropeptides (vasoactive intestinal peptide and substance P) at the arterial level. DESIGN: Prospective, clinical study. SETTING: Department of Gynecology and Obstetrics and Pathophysiology of Human Reproduction, University of Naples "Federico II," Naples, Italy. PATIENT(S): Twenty premenopausal women and 20 postmenopausal women, matched for age and parity. INTERVENTION(S): All patients underwent abdominal hysterectomy with bilateral oophorectomy for benign conditions. During surgery, a sample of uterine artery was obtained. The presence of E2, estrogen receptor alpha (ER alpha), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and S100 (a generic neuronal marker) was evaluated by means of immunohistochemistry and Western-blot analysis. MAIN OUTCOME MEASURE(S): Mean arterial content of E2, ER alpha, VIP, NPY, and SP. RESULT(S): Both immunohistochemical and Western-blot analysis showed that after menopause, the reduction in E2 and ER alpha in the uterine artery wall is associated with a decrease in vasodilator neuropeptides and an increase in vasoconstrictor NPY. A similar immunopositivity for S100 was observed in pre- and postmenopausal samples, which demonstrated similar total neuronal fiber contents. CONCLUSION(S): Postmenopausal hypoestrogenism seems to increase arterial vascular tone through a reduction of vasodilator neuropeptides and an increase in vasoconstrictor peptides in the arterial-wall termination of the autonomous system. These changes in neuropeptide content in the arterial walls might represent a new mechanism underlying the negative effects of menopause on the cardiovascular system. PMID- 17336973 TI - Late stages of embryo progression are a much better predictor of clinical pregnancy than early cleavage in intracytoplasmic sperm injection and in vitro fertilization cycles with blastocyst-stage transfer. AB - OBJECTIVE: To define and validate metrics of embryo progression and morphology during extended embryo culture and to compare the effects of early cleavage (EC) vs. blastulation stages on clinical pregnancy. DESIGN: Retrospective observational study. SETTING: University-affiliated assisted reproduction center. PATIENT(S): One thousand two hundred ninety-two intracytoplasmic sperm injection and 842 IVF blastocyst-transfer cycles. INTERVENTION(S): The embryo progression index (EPI) was calculated as the area under the curve of total cell number (TCN) over time, by using observed TCN for cleavage-stage embryos and estimated blastocyst TCN according to morphology. The EPI from days 1-3 measured early cleavage, and blastulation was assessed by EPI over extended embryo culture. Blastocyst morphology was converted into numerical blastocyst quality scores (BQSs). Receiver operating characteristic curve analysis was used to evaluate predictors for clinical pregnancy. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Per-cycle mean EPI and mean BQS for all embryos developing into blastocysts, as well as mean BQS of the transferred embryos, were significant predictors of clinical pregnancy in intracytoplasmic sperm injection and IVF cycles. Mean EPI for days 1-3 did not predict outcome. CONCLUSION(S): Early cleavage is a putative marker of embryo quality. Late-stage embryo development is more sensitive and specific in predicting clinical pregnancy than is early cleavage, supporting the use of extended embryo culture for embryo selection. The embryo progression index and BQS may also be used for this purpose. PMID- 17336974 TI - Wall discontinuities and increased expression of vascular endothelial growth factor-A and vascular endothelial growth factor receptors 1 and 2 in endometrial blood vessels of women with menorrhagia. AB - OBJECTIVE: To investigate whether the structure or regulation of the growth of endometrial blood vessels might be abnormal in women with idiopathic menorrhagia (IM). Perturbation of angiogenesis is associated with IM. DESIGN: Prospective, clinical study. SETTING: Department of gynecology at a university hospital. PATIENT(S): Twenty-four patients with IM, and 18 women with eumenorrhea. INTERVENTION(S): Endometrial biopsy samples underwent immunohistochemical staining for CD34, CD31, von Willebrand factor, vascular endothelial growth factor (VEGF)-A, and VEGF receptors 1 and 2. MAIN OUTCOME MEASURE(S): Differences in immunostaining for these markers by computer-assisted stereological analysis. RESULT(S): Endometrial vessels in patients and controls manifested focal discontinuities, or gaps, in endothelial staining for CD34, CD31, and von Willebrand factor. Electron and confocal microscopy revealed that perivascular cells, probably pericytes, covered these gaps in the vessel wall. The relative size of the gaps was significantly greater in patients with IM than in controls. Vessel circumference was also larger, and more vessels were positive for VEGF-A and for VEGF receptors 1 and 2, in patients than in controls. Gap size was significantly correlated with the number of vessels expressing VEGF-A or VEGF receptor 1. CONCLUSION(S): Endometrial blood vessels possess a discrete morphology that is characterized by endothelial gaps, and these gaps [1] are more pronounced in women with IM, [2] are related to overexpression of VEGF-A and VEGF receptor 1, and [3] might contribute to IM, e.g., by destablizing vessels. PMID- 17336975 TI - Investigation of hypothalamo-pituitary-gonadal axis and glucose intolerance among the first-degree female relatives of women with polycystic ovary syndrome. AB - OBJECTIVE: To assess the glucose intolerance and the hypothalamo-pituitary gonadal (HPG) axis in the first-degree relatives (FDRs) of patients with polycystic ovary syndrome (PCOS). DESIGN: Clinical study of the female FDRs of patients with PCOS. SETTING: Outpatients at endocrinology department of a university hospital. PATIENT(S): Seventy FDRs of PCOS patients and 20 healthy women were evaluated. INTERVENTION(S): Basal hormonal investigations, buserelin test, and 75-g oral glucose tolerance test (OGTT) were performed. MAIN OUTCOME MEASURE(S): Basal hormone levels were measured. Additionally, insulinogenic index, glucose and insulin responses to OGTT, and FSH, LH, E(2), and 17-OHP responses to buserelin test were obtained. RESULT(S): Four (5.7%) of the FDRs showed impaired glucose tolerance, and the FDRs had significantly higher fasting plasma glucose (P<.05) and basal insulin (P<.01) than control subjects. Peak and area-under-the-curve (AUC) insulin (P<.001) and AUC glucose (P<.05) responses to OGTT were also significantly higher in the FDRs than in control subjects. The FDRs showed higher insulinogenic index than the control subjects (P<.001). The FDRs had significantly (P<.05) higher LH and DHEAS levels and lower (P<.005) 17 OHP levels than the control subjects. Peak (P<.05) and AUC (P<.01) LH responses to buserelin testing were lower in the FDRs than in the control subjects while peak (P<.05) and AUC (P<.01) E(2) responses to buserelin were higher in the FDRs than in the control subjects. CONCLUSION(S): These data support the hypothesis that FDRs of PCOS patients may have insulin resistance and the HPG axis is more susceptible than in control subjects. The FDRs also have an increased prevalence of hyperandrogenism and high DHEAS levels compared with the background population. PMID- 17336976 TI - Preimplantation genetic diagnosis for Zellweger syndrome. AB - OBJECTIVE: To report on the first live birth of a normal child after performance of preimplantation genetic diagnosis (PGD) for Zellweger syndrome (ZS). DESIGN: Case report. SETTING: Tertiary-care hospital. PATIENT(S): A family with four children diagnosed with ZS, who were all born at term and who expired around 4 months of age. INTERVENTION(S): In vitro fertilization and preimplantation genetic diagnosis. MAIN OUTCOME MEASURE(S): Preimplantation genetic diagnosis of ZS in embryos, and live birth from the transferred normal embryos. RESULT(S): After PGD, two genotypically normal embryos were transferred back to the mother. Pregnancy ensued, and a healthy baby girl was delivered in week 40 of pregnancy. The baby was confirmed as genotypically wild-type, and free of any sign of ZS. CONCLUSION(S): To the best of our knowledge, this is the first successful PGD for ZS caused by mutation in PEX26 gene, with the subsequent delivery of a homozygous normal baby. PMID- 17336977 TI - Aromatase expression in endometriotic tissues and its relationship to clinical and analytical findings. AB - OBJECTIVE: To study the relationship between aromatase expression in endometriotic tissues and clinical and laboratory findings. DESIGN: Prospective basic and clinical research. SETTING: University hospital. PATIENT(S): Sixty-two women with endometriosis, and 12 without endometriosis. INTERVENTION(S): Conservative surgery, or hysterectomy and adnexectomy, along with an immunohistochemical study of aromatase in endometriotic and nonendometriotic tissues. MAIN OUTCOME MEASURE(S): Symptoms of the disease, ultrasound and surgical findings, values of tumor markers, steroids and immunoglobulins, and recurrences after surgery. RESULT(S): We observed positive immunohistochemical expression for aromatase in endometriotic tissues from 38 patients (61.3%). Aromatase expression was negative in the rest of the tissues studied and in the 12 cases without endometriosis. Aromatase-positive patients had a higher number of endometriomas, more bilaterality, and more moderate-to-severe chronic pelvic pain. Also, infertility and associated leiomyomas were more frequent in these patients, though without significant differences. There were no differences in recurrence of the disease 1 year later. Estradiol and PRL levels were significantly higher, and IgG values lower, than in aromatase-negative patients. High values of blood sedimentation rate were more frequent in aromatase-negative patients. CONCLUSION(S): Molecular alterations such as the presence of aromatase in endometriotic tissues could be involved in the development or maintenance of endometriosis. Our findings suggest major severity, activity, and chronic pelvic pain in patients with aromatase in endometriotic tissue. PMID- 17336978 TI - Pioglitazone reduces the adrenal androgen response to corticotropin-releasing factor without changes in ACTH release in hyperinsulinemic women with polycystic ovary syndrome. AB - OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA) axis seems to hyperfunction at both central and peripheral levels in polycystic ovary syndrome (PCOS). Hyperinsulinemia is involved in the adrenal hyper-responsiveness to ACTH. The present study was performed to investigate the role of insulin in the derangement of the hypothalamic-pituitary compartment of the HPA axis in PCOS. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Fifteen hyperinsulinemic PCOS women. INTERVENTION(S): Hormonal and lipid assays, oral glucose tolerance test, and corticotropin-releasing factor (1 microg/kg CRF) test before and after 4 months of treatment with the insulin sensitizer pioglitazone (30 mg/day). MAIN OUTCOME MEASURE(S): Glycemic and insulinemic response to glucose load; pituitary and adrenal response to CRF. RESULT(S): We observed a significant reduction in insulin secretion after therapy. Pioglitazone administration did not modify ACTH and cortisol response to CRF. A significant reduction in the adrenal CRF-induced secretion of androstenedione (A) (area under the curve [AUC] 202.76 +/- 78.68 ng/mL x 90 minutes to 147.05 +/- 52.06 ng/mL x 90 minutes) and 17OH-progesterone (AUC 152.92 +/- 59.56 ng/mL x 90 minutes to 117.10 +/- 63.25 ng/mL x 90 minutes') occurred after treatment. A trace response to CRF was observed for DHEAS and testosterone both before and after pioglitazone. CONCLUSION(S): In PCOS subjects, insulin may enhance adrenal steroidogenesis by acting directly on the peripheral gland, with no significant effects on the pituitary response to CRF stimulation. PMID- 17336979 TI - Clinicopathologic characteristics of uterine adenomyoma in pregnant women. AB - OBJECTIVE: To study the clinicopathologic characteristics and the treatment means of pregnant women with uterine adenomyoma. DESIGN: Retrospective, consecutive, controlled study. SETTING: University hospital for obstetrics and gynecology. PATIENT(S): Eighteen pregnant women with uterine adenomyoma. INTERVENTION(S): Data collection and statistical analysis. MAIN OUTCOME MEASURE(S): Eighteen pregnant women with uterine adenomyoma were diagnosed by excision of adenomyoma tissue during cesarean section and histopathology. The 18 subjects were retrospectively divided into treatment group (achieving this pregnancy by treatment; 10 cases) and control group (having no difficulty conceiving; 8 cases). The clinicopathologic characteristics and treatment means of the patients were analyzed retrospectively. RESULT(S): The mean volume of uterine adenomyoma in the treatment group was larger than that of the control group. The methods of treating women with uterine adenomyoma-associated infertility include GnRH agonist (GnRH-a: 6 cases), GnRH-a and IVF and embryo transfer (3 cases), and traditional Chinese medicines (1 case). CONCLUSION(S): Severe uterine adenomyoma correlate with infertility in women of childbearing age. GnRH-a is effective in treating women with uterine adenomyoma-associated infertility. PMID- 17336980 TI - Embryonic adhesion is not affected by endometrial leptin receptor gene silencing. AB - OBJECTIVE: In rodents, evidence suggests that the leptin system is mandatory for embryonic implantation. We aimed to investigate the functional relevance of the endometrial leptin receptor (OB-R) in the adhesion phase of human implantation. DESIGN: We used an in vitro model for embryonic adhesion, composed of a human endometrial cell line (HEC1-A) and B6C3F1 mouse embryos. The OB-R gene was silenced in a stable manner by RNA interference, and embryonic adhesion rates were analyzed. SETTING: Research laboratory at a university-affiliated center. INTERVENTION(S): RNA interference. MAIN OUTCOME MEASURE(S): Embryonic adhesion in cells treated with OB-R RNAi. RESULT(S): The OB-R shRNA-transfected cells exhibited up to 80% lower OB-R mRNA levels than those of cells nontransfected or transfected with scrambled shRNA. The OB-R protein was also highly diminished in the stable OB-R shRNA-transfected HEC1A cells, whereas OAS1 expression was similar in both nontransfected and transfected cells. Embryonic adhesion rate was similar in nontransfected (94%) and HEC1-A transfected cells with a scrambled sequence (94%) or with OB-R silencing sequence (92%). CONCLUSION(S): Knocking down the OB-R gene in a human endometrial cell line has no effect on the embryonic adhesion rate. Nevertheless, the functional relevance of this system can not be excluded in other phases of embryonic implantation, such as the invasion phase. Moreover, we describe a new approach to the functional analysis of candidate molecules implicated in blastocyst adhesion. PMID- 17336981 TI - Characterisation of the sympathetic nervous system of Asian (Elephas maximus) and African (Loxodonta africana) elephants based on urinary catecholamine analyses. AB - Assessing the welfare status of captive animals using non-invasive measurements of hormones is of growing interest because this can serve as an effective tool to facilitate the optimization of environmental and husbandry conditions. Both the African elephant (Loxodonta africana) and the Asian elephant (Elephas maximus) exhibit extremely low breeding success in captivity, and because elevated levels of stress may negatively influence reproductive functions, this study sought to establish a method for assessing sympathoadrenal activity in captive female elephants. We found a circadian variation in urinary noradrenaline (norepinephrine, NE), adrenaline (epinephrine, Epi) and dopamine (DA) under short day length. Peak activity of noradrenaline and dopamine was noted at 3 a.m. Adrenaline showed a biphasic pattern with a minor peak recorded at 3 a.m. and a major peak 9 a.m. Under long-day photoperiodic conditions, simultaneous peaks of noradrenaline and adrenaline were again noted at 3 a.m. whereas dopamine does not appear to have a distinct circadian pattern under long-day length. A transfer of two elephant cows resulted in a marked increase in urinary adrenaline and noradrenaline levels, confirming that the transfer represented a stressful event. During the peripartal period, noradrenaline concentrations increased and maximum concentrations were obtained at delivery. Daily measurements of urinary dopamine throughout the follicular phase revealed an increase in dopamine secretion close to ovulation. This increase might indicate a role of dopamine in the ovulatory mechanisms. These results suggest that changes in urinary catecholamine excretion reflect fluctuations in sympathoadrenal activity and may be a useful indicator of stress. PMID- 17336982 TI - Existence of leptin receptor protein in chicken tissues: isolation of a monoclonal antibody against chicken leptin receptor. AB - Leptin receptor belongs to the class I cytokine receptor superfamily, which mediates multiple physiological roles in mammals. However, the leptin system is poorly understood in birds, as the evidence for the existence of a natural ligand of the receptor in birds is controversial. As part of a strategy to reveal the physiological significance of leptin in birds, we isolated a monoclonal antibody (mAb) against a chicken leptin receptor (chLEPR). Based on the cDNA sequence for chLEPR, a peptide coding for the cytoplasmic domain of chLEPR was expressed in Escherichia coli and this was used to immunize mice to obtain the mAb. The anti chLEPR mAb recognized proteins migrated at approximately 180 kDa by Western blot analysis using cellular extracts prepared from COS-7 cells transfected with chLEPR expression vector. By Western blot analysis using the same mAb, an immunoreactive band migrated at 180 kDa was detected in the chicken brain and Leghorn male hepatoma (LMH) cells, and which was similar to the size observed in the in vitro transfection study. Taken together, the chLEPR mAb obtained in the present study cross-reacted, at least, with long isoform chLEPR, suggesting that LEPR mRNA expressed in chicken tissues is likely to be translated. The chLEPR mAb, which has not been described elsewhere, enables us to explore the expression and localization of the receptor in the chicken tissues at the protein level. Therefore, this antibody would be a powerful tool in studying and understanding the regulation and function of leptin and its receptors in birds. PMID- 17336983 TI - Expression of hormone genes and osmoregulation in homing chum salmon: a minireview. AB - Pacific salmon migrate from ocean through the natal river for spawning. Information on expression of genes encoding osmoregulatory hormones and migratory behavior is important for understanding of molecular events that underlie osmoregulation of homing salmon. In the present article, regulation of gene expression for osmoregulatory hormones in pre-spawning salmon was briefly reviewed with special reference to neurohypophysial hormone, vasotocin (VT), and pituitary hormones, growth hormone (GH) and prolactin (PRL). Thereafter, we introduced recent data on migratory behavior from SW to FW environment. In pre spawning chum salmon, the hypothalamic VT mRNA levels increased in the males, while decreased in the females with loss of salinity tolerance when they were kept in SW. The amounts of GH mRNA in the pituitary decreased during ocean migration prior to entrance into FW. Hypo-osmotic stimulation by SW-to-FW transfer did not significantly affect the amount of PRL mRNA, but it was elevated in both SW and FW environments along with progress in final maturation. Behaviorally, homing chum salmon continued vertical movement between SW and FW layers in the mouth of the natal river for about 12h prior to upstream migration. Pre-spawning chum salmon in an aquarium, which allowed fish free access to SW and FW, showed that individuals with the lower plasma testosterone (T) and higher estradiol-17beta (E2) levels spent longer time in FW when compared with the SW fish. Taken together, neuroendocrine mechanisms that underlie salt and water homeostasis and migratory behavior from SW to FW may be under the control of the hypothalamus-pituitary-gonadal axis in pre-spawning salmon. PMID- 17336984 TI - Host specificity of two species of Gnathia (Isopoda) determined by DNA sequencing blood meals. AB - Host specificity data for gnathiid isopods are scarce because the parasitic stages are difficult to identify and host-parasite contact is often brief. We examined two common nocturnal species, Gnathia falcipenis and Gnathia sp. C, collected in light traps from two locations at Lizard Island on the Great Barrier Reef, Australia. Engorged third stage gnathiids were photographed and permitted to moult into adults to allow identification. We compared approximately 580 bp sequences of 16S mtDNA from blood meals with host sequences available on GenBank using BLASTn. Where homology was <98%, familial identity was investigated with neighbour-joining trees. All blood meal sequences (n=60) and homologous fish sequences (n=87) from GenBank were used in a Bayesian analysis, which identified all but three sequences to family. The host frequency distributions used by each species were significantly different; only four host families were shared. No gnathiids fed on elasmobranchs, blennies or apogonids, and most fed on host families whose representatives are typically large. Gnathia sp. C showed a distinct predilection for nemipterids. Gnathia falcipenis often parasitised sand dwelling families, and unlike sympatric diurnal gnathiid species, it also frequently parasitised pomacentrids. We conclude that G. falcipenis and Gnathia sp. C operate as generalist micropredators with preferences. PMID- 17336986 TI - Blood donation, body iron status and carotid intima-media thickness. AB - Iron could promote free radical formation, which may lead to injury of the arterial wall and atherosclerosis. Blood donation may reduce cardiovascular risk by lowering body iron status. We collected data on blood donation history and intima-media thickness of the common carotid artery (CIMT) in 819 subjects (50-70 years), who were recruited from municipal and blood bank registries in The Netherlands. Serum iron parameters were assessed, including non-transferrin bound iron (NTBI) that has recently been found in conditions of iron overload. Serum ferritin was lower in current donors (n=443; 44 microg/L) than in ex-donors (n=120; 114 microg/L) and never-donors (n=256; 124 microg/L, P for trend <0.001). For NTBI, values were 2.33, 2.54, and 2.51 micromol/L, respectively (P<0.05). CIMT was slightly reduced in frequent donors (i.e., > or =49 times during life or > or =2 times per year), although not statistically significant. CIMT was not significantly related to NTBI. Frequent blood donation, resulting in lowered body iron, might give some protection against accelerated atherosclerosis. PMID- 17336985 TI - IrAE: an asparaginyl endopeptidase (legumain) in the gut of the hard tick Ixodes ricinus. AB - Ticks are ectoparasitic blood-feeders and important vectors for pathogens including arboviruses, rickettsiae, spirochetes and protozoa. As obligate blood feeders, one possible strategy to retard disease transmission is disruption of the parasite's ability to digest host proteins. However, the constituent peptidases in the parasite gut and their potential interplay in the digestion of the blood meal are poorly understood. We have characterised a novel asparaginyl endopeptidase (legumain) from the hard tick Ixodes ricinus (termed IrAE), which we believe is the first such characterisation of a clan CD family C13 cysteine peptidase (protease) in arthropods. By RT-PCR of different tissues, IrAE mRNA was only expressed in the tick gut. Indirect immunofluorescence and EM localised IrAE in the digestive vesicles of gut cells and within the peritrophic matrix. IrAE was functionally expressed in Pichia pastoris and reacted with a specific peptidyl fluorogenic substrate, and acyloxymethyl ketone and aza-asparagine Michael acceptor inhibitors. IrAE activity was unstable at pH > or = 6.0 and was shown to have a strict specificity for asparagine at P1 using a positional scanning synthetic combinatorial library. The enzyme hydrolyzed protein substrates with a pH optimum of 4.5, consistent with the pH of gut cell digestive vesicles. Thus, IrAE cleaved the major protein of the blood meal, hemoglobin, to a predominant peptide of 4kDa. Also, IrAE trans-processed and activated the zymogen form of Schistosoma mansoni cathepsin B1 -- an enzyme contributing to hemoglobin digestion in the gut of that bloodfluke. The possible functions of IrAE in the gut digestive processes of I. ricinus are compared with those suggested for other hematophagous parasites. PMID- 17336987 TI - Effect of a common X-linked angiotensin II type 2-receptor gene polymorphism ( 1332 G/A) on the occurrence of premature myocardial infarction and stenotic atherosclerosis requiring revascularization. AB - OBJECTIVES: To assess the association of the angiotensin II type 2 (AT2) receptor (-1332 G/A) gene polymorphism with premature coronary artery disease (CAD) and investigate for a further role in both myocardial infarction and predominantly stenotic atherosclerosis requiring revascularisation. METHODS AND RESULTS: We investigated 885 families, which consisted of at least one sibling affected with premature CAD and at least one unaffected sibling. Genotyping of subjects was performed using a restriction enzyme digestion of an initial 310 bp PCR fragment that included the AT2 (-1332 G/A) locus. The mean age of the 1143 individuals affected by premature CAD at the time of event was 50.6+/-9.1 years. The genetic data were analyzed for these families using the X-linked sibling transmission disequilibrium test (XS-TDT). We observed significant evidence for an association for the AT2 (-1332 G) locus and premature CAD (p-exact value=0.028). This was driven by a highly significant result in men (p-exact value=0.005). We performed further analyses to investigate for an association with myocardial infarction (Group 1) and stenotic atherosclerosis that was of sufficient severity as to require revascularization (Group 2). We found an increase in the frequency of the G/GG genotype in both Groups 1 and 2, being most marked in Group 2 (XS-TDT, p exact value=0.0134); logistic regression (p=0.033, OR 1.38; 95% CI of 1.212 1.507). CONCLUSION: We have observed evidence of association between the X-linked AT2 (-1332 G/A) polymorphism and premature CAD with further evidence of a statistically significant association with stenotic atherosclerosis requiring revascularization. PMID- 17336988 TI - Fractionation of cholesteryl ester rich intermediate density lipoprotein subpopulations by chondroitin sulphate. AB - IDL is considered an atherogenic lipoprotein but little progress has been made on methods to subfractionate this density class. Furthermore, previous work suggests that lipoproteins retained by the arterial wall, of which chondoitin sulphate is the major arterial wall proteoglycan, are potentially atherogenic. The aim of this study was to assess the subfractionation of IDL particles using chondroitin sulphate (CS). Forty healthy subjects were recruited from laboratory staff and/or their partners. Fasted plasma samples were obtained and IDL (1.006 g/ml0.05). To assess the test-retest reliability, the scores of two FIS applications did not differ statistically (cognitive t=1.948 p>0.05, physical t=1.420 p=0.160, social t=1.470 p=0.146, total t=1.990 p=0.05). Intraclass correlation coefficients were 0.89 (99% confidence interval: 0.79 0.94) for cognitive, 0.95 (0.91-0.97) for physical, 0.91 (0.83-0.95) for social, and 0.93 (0.86-0.96) for total FIS scores (p<0.001). EDSS correlated with physical subscores in both applications of FIS. CONCLUSION: Turkish version of FIS, which is valid and reliable, seems an appropriate tool for the assessment of the effects of fatigue in Turkish MS population. PMID- 17337009 TI - Does EEG (visual and quantitative) reflect mental impairment in subcortical vascular dementia? AB - The aim of this study was to determine if the results of visual and quantitative EEG (QEEG) parameters reveal a correlation with mental impairment in subcortical vascular dementia (SVD), one of the most frequent causes of cognitive impairment in the elderly. In SVD, like in Alzheimer's disease disturbances were found in cholinergic transmission. The cholinergic deficit as manifested in changes of synaptic potentials is reflected in EEG signals. MATERIAL: 31 patients with probable SVD (according to NINCDS-AIREN and T. Erkinjuntii's criteria) and mean age 72.3 yrs;(M--43%, F--57%) and 14 healthy control subjects with mean age of 72.3 yrs (M-57%, F-43%). According to the Mini Mental Scale Examination (MMSE) the SVD group was divided into two subgroups with mild and moderate dementia, their EEGs being recorded with a Medelec and Neuroscan 4.2 system. Visual EEG findings were classified with the use of eight-degree scale of pathological changes by the presence of slow waves. Then QEEGs were made. The following parameters were calculated: alpha/slow wave power ratios, the mean wave frequency in all and in some selected derivations. RESULTS: A significant difference was found between QEEGs in SVD subgroups with mild and moderate dementia (p<0.05), but there was no significant difference between visual EEGs. A significant correlation between QEEG parameters such as alpha/slow wave ratio or mean wave frequency and mental impairment (according to MMSE results) was found (p<0.001), but there was no significant correlation between degree of EEG abnormalities in visual analysis and MMSE results. CONCLUSION: Only QEEGs are correlated with mental impairment in SVD. Visual EEG technique as a less precise tool does not reflect the mental impairment in SVD due to cholinergic deficit. PMID- 17337008 TI - Vascular oxidative stress in Alzheimer disease. AB - Alzheimer disease and cerebrovascular dementia are two common causes of dementia and, by present diagnostic criteria, are mutually exclusive using vascular pathology as an arbitrary demarcation in differential diagnosis. However, evidence from epidemiological, neuropathological, clinical, pharmacological, and functional studies suggest considerable overlap in risk factors and pathological changes suggesting shared common pathogenic mechanisms between these two diseases such that vascular factors play a vital role in the pathogenesis of Alzheimer disease. A high energy demand and lack of an endogenous fuel reserve make the brain highly dependent upon a continuous blood supply where disruption of cerebral blood vessels and blood flow can have serious consequences on neural activities. Indeed, many studies implicate metabolic defects in Alzheimer disease, such a reduced brain metabolism is one of the best documented abnormalities in the disease. Notably, since endothelial reactive oxygen species such as nitric oxide act as vasodilators at low concentrations, increased production coupled with elevated reactive oxygen species scavenging of nitric oxide, can lead to reduced bioavailability of nitric oxide and increased oxidative stress that damage sensitive vascular cells. In this respect, we and others have demonstrated that oxidative stress is one of the earliest pathological changes in the brain of Alzheimer disease patients and plays a critical role in the vascular abnormalities underlying metabolic defects in Alzheimer disease. Here, we discuss vascular factors in relation to Alzheimer disease and review hypoperfusion as a potential cause by triggering mitochondrial dysfunction and increased oxidative stress initiating the pathogenic process. PMID- 17337010 TI - Apolipoprotein E epsilon4 allele frequency in elderly depressed patients with and without cerebrovascular disease. AB - Late-onset depression (LOD) could be a very early manifestation of Alzheimer's disease (AD), although contradictory results have been reported. Cerebrovascular disease (CVD) may favor the development of LOD, and that the particular forms of vascular depression should be individualized. The Apolipoprotein E (ApoE) epsilon4 allele was shown to be a risk factor for AD. Its role in LOD is controversial, while it is still unknown in vascular depression. Our objective was to clarify the relationship between ApoE epsilon4 allele and LOD in patients with and without CVD. We examined the ApoE phenotypes in a sample of 311 subjects: 50 with vascular LOD, 24 with LOD without CVD, 115 with AD and 122 normal controls (NC). The study of the ApoE epsilon4 allele frequency showed significant differences between: AD group and the vascular LOD and NC groups; LOD group without CVD compared with NC group (p<0.05 to 0.001). The frequency of the epsilon4 allele in the LOD group without CVD did not differ significantly from the AD group, similarly the frequency of the epsilon4 allele in the vascular LOD group was not different from that in NC. The study suggests an association between the ApoE epsilon4 allele and the LOD without CVD. These patients could be at risk of developing AD by an epsilon4-dependent pathway. In contrast, the results show no association between the presence of ApoE epsilon4 allele and vascular depression and provide further evidence in support of the concept that ApoE epsilon4 allele is not associated with clinical CVD. PMID- 17337011 TI - The potential for signal integration and processing in interacting MAP kinase cascades. AB - The cellular response to environmental stimuli requires biochemical information processing through which sensory inputs and cellular status are integrated and translated into appropriate responses by way of interacting networks of enzymes. One such network, the mitogen-activated protein (MAP) kinase cascade is a highly conserved signal transduction module that propagates signals from cell surface receptors to various cytosolic and nuclear targets by way of a phosphorylation cascade. We have investigated the potential for signal processing within a network of interacting feed-forward kinase cascades typified by the MAP kinase cascade. A genetic algorithm was used to search for sets of kinetic parameters demonstrating representative key input-output patterns of interest. We discuss two of the networks identified in our study, one implementing the exclusive-or function (XOR) and another implementing what we refer to as an in-band detector (IBD) or two-sided threshold. These examples confirm the potential for logic and amplitude-dependent signal processing in interacting MAP kinase cascades demonstrating limited cross-talk. Specifically, the XOR function allows the network to respond to either one, but not both signals simultaneously, while the IBD permits the network to respond exclusively to signals within a given range of strength, and to suppress signals below as well as above this range. The solution to the XOR problem is interesting in that it requires only two interacting pathways, crosstalk at only one layer, and no feedback or explicit inhibition. These types of responses are not only biologically relevant but constitute signal processing modules that can be combined to create other logical functions and that, in contrast to amplification, cannot be achieved with a single cascade or with two non-interacting cascades. Our computational results revealed surprising similarities between experimental data describing the JNK/MKK4/MKK7 pathway and the solution for the IBD that evolved from the genetic algorithm. The evolved IBD not only exhibited the required non-monotonic signal strength-response, but also demonstrated transient and sustained responses that properly reflected the input signal strength, dependence on both of the MAPKKs for signaling, phosphorylation site preferences by each of the MAPKKs, and both activation and inhibition resulting from the overexpression of one of the MAPKKs. PMID- 17337013 TI - [Temporopolar epidural transcavernous transpetrous approach. Technique and indications]. AB - BACKGROUND AND PURPOSE: Several selective approaches have been recommended for access to the petroclival region (PCR). However, locoregional extension of the tumor may necessitate more extensive procedures. Dissections from injected specimens allowed us to describe the different osteodural triangles that are exposed to provide an extensive access to the PCR. METHOD: The bony step included a temporopterional flap and exposure of the paraclinoid carotid after removal of the anterior clinoid process. The sphenoid wing was then extensively drilled, exposing the foramen rotundum and ovale. An anterior petrosectomy was subsequently performed. The dura propria of the cavernous sinus was elevated as far as the Meckel cave. The sylvian fissure was also opened. Then, the temporobasal dura and the dura from the posterior surface of the petrous bone were opened and the superior petrosal sinus was coagulated and divided. The tentorium was divided toward its free edge. RESULTS: Via this approach, cranial nerves from the olfactory tract to the acousticofacial bundle are exposed. In the same way, the ventral and lateral surface of the pons is identified. CONCLUSION: The epidural temporopolar transcavernous transpetrous approach is useful to expose during the same procedure, elements of the posterior and middle cranial fossa. It is of particular value when managing tumors simultaneously involving the PCR, the parasellar, and the suprasellar regions. PMID- 17337012 TI - Multi-tasking on chromatin with the SAGA coactivator complexes. AB - Over the past 10 years, much progress has been made to understand the roles of the similar, yet distinct yeast SAGA and SLIK coactivator complexes involved in histone post-translational modification and gene regulation. Many different groups have elucidated functions of the SAGA complexes including identification of novel components, which have conferred additional distinct functions. Together, recent studies demonstrate unique attributes of the SAGA coactivator complexes in histone acetylation, methylation, phosphorylation, and deubiquitination. In addition to roles in transcriptional activation with the 19S proteasome regulatory particle, recent evidence also suggests functions for SAGA in elongation and mRNA export. The modular nature of SAGA allows this approximately 1.8 MDa complex to organize its functions and carry out multiple roles during transcription, particularly under conditions of cellular stress. PMID- 17337014 TI - [Anesthesia for video-assisted surgery of the thoracic and lumbar spine: a survey of 44 patients]. AB - INTRODUCTION: The development of video-assisted surgery of the dorsolumbar spine has led to the need for adaptations for appropriate anesthetic management. Data concerning anesthesia for such surgery is very sparse in the literature. AIM OF THE STUDY: The aim of this retrospective study of 44 patients was to learn more about anesthesia practices used for patients undergoing this type of surgery. PATIENTS AND METHOD: The files of 44 patients were studied retrospectively. Epidemiologic data and the perioperative phase were analysed. RESULTS: The preoperative phase was not specific with preoperative assessment adapted to each patient. Similarly, monitoring practices during the surgical procedure were not specific. The choice of the anesthetic agents depended on the patient's clinical status. For tracheal intubation, care was taken to enable lung exclusion, even if not often used. Thoracic drainage at the end of the surgery was required in the event of imperfect hemostasis and in selected patients was replaced by pneumothorax exsufflation during closure. The postoperative period was uneventful and did not require admission to intensive care; non-specific analgesia was used. DISCUSSION: Adaptations of anesthetic practices are required each time a new surgical technique is developed. Excepting lung exclusion, anesthesia for video assisted dorsolumbar spine surgery is not specific. PMID- 17337015 TI - [Chordoid meningioma. Two cases]. AB - Chordoid meningioma is an uncommon histopathological variant of meningioma frequently confused with chordoma. Recurrence is not uncommon. The aim of our study is to present the clinical and pathological characteristics of this entity and a review of the literature. We report two cases of chordoid meningioma occurring in two women aged 47 and 63 years. Both women presented neurological signs without systemic disease. Radiological findings were temporoparietal and temporofrontal lesions with intense enhancement after contrast injection. Complete surgical resection was performed. Histopathologic findings were consistent with chordoid meningioma. PMID- 17337016 TI - [Primitive intracranial trigeminal nerve germinoma. Case report]. AB - A 22-year-old man presented headache, asthenia, body weight loss and trigeminal hypoesthesia worsening quickly. Radiological analysis showed an enhanced lesion that originated from the cavernous sinus and extended into the Meckel cave, owing to the fifth cranial nerve's course. The lesion was explored by a temporo pterional approach and was partially removed. On the basis of histological analysis and negativity of tumor marker levels in serum and cerebrospinal fluid (alpha-fetoprotein alpha, human beta-chorionic gonadotropin), a primitive non secreting intracranial germinoma was diagnosed. Under combined chemotherapy (carboplatine, ifosfamide, etoposide) followed by focal fractionated radiotherapy delivering 40 Gy to the initial tumor volume, the outcome was excellent. Five years later, the patient was in complete clinical and radiological remission. Primitive intracranial germinomas are rare malignant tumors involving mainly pineal and hypothalamic regions. We report a case of intracranial trigeminal nerve germinoma. To the best of our knowledge, no case of primitive germinoma was previously described in this location. Aspects of diagnosis and treatment are discussed in the light of previous publishing data. PMID- 17337017 TI - [Multilevel costovertebral echinococcosis: effectiveness of a combined approach]. AB - Hydatid disease generally involves the liver and the lung, but rarely can be encountered in bones. The disease predominantly occurs in vascularized areas, involving in descending order: vertebrae, long bones, ilium, skull, and ribs. Vertebral and rib hydatidosis may result from vascular or lymphatic migration of a fertile cell from a hepatic focus. In humans, the two main forms are due to Echinococcus granulosis and less frequently, E. multilocularis (alveolaris). The hydatid cysts usually grow slowly asymptomatically and compression of the involved or the neighboring organ causes clinical manifestations. In this patient, hydatid disease occurred in the chest wall with secondary spinal canal involvement successfully treated by removal of cysts via T7, T8, T9, T10, and T11 laminectomies via a posterior approach, followed by resection of the involved ribs. Total removal of cysts without rupture appears to provide effective protection against late recurrences. PMID- 17337018 TI - Antiepileptic drugs and muscarinic receptor-dependent excitation in the rat subiculum. AB - Field and intracellular recordings were made in an in vitro slice preparation to establish whether the antiepileptic drugs topiramate and lamotrigine modulate cholinergic excitation in the rat subiculum. Bath application of carbachol (CCh, 70-100microM) induced: (i) spontaneous and synchronous field oscillations (duration=up to 7s) that were mirrored by intracellular depolarizations with rhythmic action potential bursts; and (ii) depolarizing plateau potentials (DPPs, duration=up to 2.5s) associated with action potential discharge in response to brief (50-100ms) intracellular depolarizing current pulses. Ionotropic glutamatergic receptor antagonists abolished the field oscillations without influencing DPPs, while atropine (1microM) markedly reduced both types of activity. Topiramate (10-100microM, n=8-13 slices) or lamotrigine (50-400microM, n=3-12) decreased in a dose-dependent manner, and eventually abolished, CCh induced field oscillations. During topiramate application, these effects were accompanied by marked DPP reduction. When these antiepileptic drugs were tested on DPPs recorded in the presence of CCh+ionotropic glutamatergic and GABA receptor antagonists, only topiramate reduced DPPs (n=5-19/dose; IC(50)=18microM, n=48). Similar effects were induced by topiramate during metabotropic glutamate receptor antagonism (n=5), which did not influence DPPs. Thus, topiramate and lamotrigine reduce CCh-induced epileptiform synchronization in the rat subiculum but only topiramate is effective in controlling DPPs. We propose that muscarinic receptor-mediated excitation represents a target for the action of some antiepileptic drugs such as topiramate. PMID- 17337019 TI - A familial factor in the development of colour agnosia. AB - An important aspect of research into the link between genes and behaviour concerns the identification of familial determination. There is evidence for familial factors in selective deficits, such as developmental dyslexia and developmental prosopagnosia. Colour agnosia concerns a selective neuropsychological condition in which colour perception is intact, while the identification and naming of colour is disrupted. We recently demonstrated that this deficit can occur as a developmental deficit. Here, we show that there is a familial factor in the development of colour agnosia by reporting the colour processing abilities of the mother and the daughters of a man with developmental colour agnosia. PMID- 17337021 TI - Individual differences in cortisol levels and performance on a test of executive function in men and women. AB - Despite evidence for a high concentration of corticosteroid receptors in prefrontal cortex, little research has examined the relationship between cortisol and prefrontal cortical function other than working memory. We investigated the association between salivary cortisol levels and performance on the Wisconsin Card Sorting Test (WCST) of executive function and on a test of mental rotation (to test specificity of the relationship between cortisol and cognitive performance) in men and women (n=116, ages 17-22). Higher cortisol levels at the beginning of the test session were associated with more errors in women on the WCST and fewer errors in men. However, men's cortisol levels were lower than women's at this point in time. Cortisol levels were not associated with mental rotation scores. Our results suggest that individual differences in cortisol levels among participants upon arrival to a test situation influence performance on a task involving the prefrontal cortex. PMID- 17337022 TI - Diterpenoids and triterpenoids from Euphorbia guyoniana. AB - Two new compounds with tigliane and cycloartane skeletons: 4,12 dideoxy(4alpha)phorbol-13-hexadecanoate (1) and 24-methylenecycloartane-3,28-diol (2), respectively, in addition of four known diterpenoids and 13 triterpenoids: 3 benzoyloxy-5,15-diacetoxy-9,14-dioxojatropha-6(17),11-diene (4), ent-abieta 8(14),13(15)-dien-16,12-olide (5), ent-8alpha,14alpha-epoxyabieta-11,13(15)-dien 16,12-olide (6), ent-3-hydroxyatis-16(17)-ene-2,14-dione (7), 3beta hydroxytaraxer-14-en-28-oic acid (8), beta-sitosteryl-3beta-glucopyranoside-6'-O palmitate (9), multiflorenyl acetate (10), multiflorenyl palmitate (11), peplusol (12), 24-methylenecycloartanol (3), lanosterol (13), euferol (14), butyrospermol (15), cycloartenol (16), obtusifoliol (17), cycloeucalenol (18) and beta sitosterol (19), were isolated from the roots of Euphorbia guyoniana. Their structures were established on the basis of physical and spectroscopic analysis, including 1D and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY) and by comparison with the literature data. PMID- 17337023 TI - Antioxidant activity of isocoumarins isolated from Paepalanthus bromelioides on mitochondria. AB - The isocoumarins (1-50 microM) paepalantine (9,10-dihydroxy-5,7-dimethoxy-1H naptho(2,3c)pyran-1-one), 8,8'-paepalantine dimer, and vioxanthin isolated from Paepalanthus bromelioides, were assessed for antioxidant activity using isolated rat liver mitochondria and non-mitochondrial systems, and compared with the flavonoid quercetin. The paepalantine and paepalantine dimers, but not vioxanthin, were effective at scavenging both 1,1-diphenyl-2-picrylhydrazyl (DPPH(*)) and superoxide (O(2)(-)) radicals in non-mitochondrial systems, and protected mitochondria from tert-butylhydroperoxide-induced H(2)O(2) accumulation and Fe(2+)-citrate-mediated mitochondrial membrane lipid peroxidation, with almost the same potency as quercetin. These results point towards paepalantine, followed by paepalantine dimer, as being a powerful agent affording protection, apparently via O(2)(-) scavenging, from oxidative stress conditions imposed on mitochondria, the main intracellular source and target of those reactive oxygen species. This strong antioxidant action of paepalantine was reproduced in HepG2 cells exposed to oxidative stress condition induced by H(2)O(2). PMID- 17337024 TI - An immunomodulating pectic polymer from Glinus oppositifolius. AB - An immunomodulating pectic polymer, GOA1, obtained from the aerial parts of the Malian medicinal plant Glinus oppositifolius (L.) Aug. DC. (Aizoaceae) has previously been reported to consist of arabinogalactans type I and II, probably linked to a rhamnogalacturonan backbone. To further elucidate the structure of the polymer GOA1, enzymatic degradation studies and weak acid hydrolysis were performed. Five different glycosidases were used, endo-alpha-D-(1-->4) polygalacturonase, exo-alpha-L-arabinofuranosidase, endo-alpha-L-(1-->5) arabinanase, endo-beta-D-(1-->4)-galactanase and exo-beta-D-galactosidase. It appears that GOA1 may contain a structural moiety consisting of a 1,3-linked galactopyranosyl (Galp) main chain with 1,6-linked Galp side chains attached to position 6 of the main chain. The 1,6-linked Galp side chain may be branched in position 3 with arabinofuranosyl (Araf) side chains. A 1,4-linked Galp backbone which might carry side chains or glycosyl units attached to position 3 is also a structural element in the polymer. We further show that GOA1 induce proliferation of B cells and the secretion of IL-1beta by macrophages, in addition to a marked increase of mRNA for IFN-gamma in NK-cells. To elucidate structure-activity relations the native polymer and the digested fractions were tested for complement fixing activity and intestinal immune stimulating activity. The partial removal of Araf residues after enzymatic degradations did not affect the bioactivities, while the acid hydrolysed fraction showed reduced complement fixing activity. A decrease in Araf units, 1,3,6-linked Galp units and a partial hydrolysed rhamnogalacturonan backbone, in addition to a reduction in molecular weight are factors that might have contributed to reduced bioactivity. PMID- 17337025 TI - The propagation of a cultural or biological trait by neutral genetic drift in a subdivided population. AB - We study fixation probabilities and times as a consequence of neutral genetic drift in subdivided populations, motivated by a model of the cultural evolutionary process of language change that is described by the same mathematics as the biological process. We focus on the growth of fixation times with the number of subpopulations, and variation of fixation probabilities and times with initial distributions of mutants. A general formula for the fixation probability for arbitrary initial condition is derived by extending a duality relation between forwards- and backwards-time properties of the model from a panmictic to a subdivided population. From this we obtain new formulae(formally exact in the limit of extremely weak migration) for the mean fixation time from an arbitrary initial condition for Wright's island model, presenting two cases as examples. For more general models of population subdivision, formulae are introduced for an arbitrary number of mutants that are randomly located, and a single mutant whose position is known. These formulae contain parameters that typically have to be obtained numerically, a procedure we follow for two contrasting clustered models. These data suggest that variation of fixation time with the initial condition is slight, but depends strongly on the nature of subdivision. In particular, we demonstrate conditions under which the fixation time remains finite even in the limit of an infinite number of demes. In many cases-except this last where fixation in a finite time is seen--the time to fixation is shown to be in precise agreement with predictions from formulae for the asymptotic effective population size. PMID- 17337026 TI - Isolation and cloning of a metalloproteinase from king cobra snake venom. AB - A 50 kDa fibrinogenolytic protease, ohagin, from the venom of Ophiophagus hannah was isolated by a combination of gel filtration, ion-exchange and heparin affinity chromatography. Ohagin specifically degraded the alpha-chain of human fibrinogen and the proteolytic activity was completely abolished by EDTA, but not by PMSF, suggesting it is a metalloproteinase. It dose-dependently inhibited platelet aggregation induced by ADP, TMVA and stejnulxin. The full sequence of ohagin was deduced by cDNA cloning and confirmed by protein sequencing and peptide mass fingerprinting. The full-length cDNA sequence of ohagin encodes an open reading frame of 611 amino acids that includes signal peptide, proprotein and mature protein comprising metalloproteinase, disintegrin-like and cysteine rich domains, suggesting it belongs to P-III class metalloproteinase. In addition, P-III class metalloproteinases from the venom glands of Naja atra, Bungarus multicinctus and Bungarus fasciatus were also cloned in this study. Sequence analysis and phylogenetic analysis indicated that metalloproteinases from elapid snake venoms form a new subgroup of P-III SVMPs. PMID- 17337027 TI - The evolution of venom-conducting fangs: insights from developmental biology. AB - The present study of the origin of the various types of fang represented among colubroid snakes (i.e., tubular, grooved, and ungrooved) attempts to reconcile the morphology of adult fangs with current phylogenetic hypotheses. Observations of growth series of developing tubular fangs were hypothesised to shed light on the evolutionary origin of fangs in snakes. While molecular phylogenies and evolutionary studies of venom proteins and of other anatomical components of the venom-delivery system reconstruct a consistent evolutionary scenario, the character of a tubular venom-conducting fang does not fit in this scenario. The present review offers a series of possible scenarios to resolve this anomaly. Of these, a new idea argues that a heterochronic mechanism (alteration of the timing of developmental events) may provide the answer that the ungrooved and grooved teeth of colubrid snakes evolved from an ancestral tubular fang by means of attachment of replacement tubular fangs to the maxilla at an earlier developmental stage than usual (precocial ankylosis). PMID- 17337028 TI - Interference in dengue virus adsorption and uncoating by carrageenans. AB - This study demonstrated that the lambda- and iota-carrageenans, sulfated polysaccharides containing linear chains of galactopyranosyl residues, are potent inhibitors of dengue virus type 2 (DENV-2) and 3 (DENV-3) multiplication in Vero and HepG2 cells, with values of effective concentration 50% from 0.14 to 4.1 microg/ml. This activity was assayed by plaque reduction, virus yield inhibition and antigen expression tests, and was independent of the input multiplicity of infection in the range 0.001-1. The inhibitory action of the lambda-carrageenan, an heparan sulfate (HS)-imitative compound, was exerted by a dual interference with virus adsorption and internalization of nucleocapsid into the cytoplasm. Although virus particles may enter the cell when compound was added after DENV-2 adsorption, as shown by intracellular uptake of radiolabeled DENV-2 particles and quantitative RT-PCR, infectious center and virion uncoating assays have shown that carrageenan-treated virions cannot be released from the endosomes. Viral protein synthesis, the first step of macromolecular synthesis after DENV entry to the host cell, was not affected by the carrageenan. Furthermore, no inhibition of virus multiplication was detected when the entry process was bypassed through DENV-2 RNA transfection into the cell. The dual sites of action of an HS-like molecule suggest that, at least in monkey kidney and human hepatic cells, the HS residues in the cell membrane appear to act as mediators for DENV-2 entry, an interesting alternative target for flavivirus therapy. PMID- 17337029 TI - Apparent motion of monocular stimuli in different depth planes with lateral head movements. AB - A stationary monocular stimulus appears to move concomitantly with lateral head movements when it is embedded in a stereogram representing two front-facing rectangular areas, one above the other at two different distances. In Experiment 1, we found that the extent of perceived motion of the monocular stimulus covaried with the amplitude of head movement and the disparity between the two rectangular areas (composed of random dots). In Experiment 2, we found that the extent of perceived motion of the monocular stimulus was reduced compared to that in Experiment 1 when the rectangular areas were defined only by an outline rather than by random dots. These results are discussed using the hypothesis that a monocular stimulus takes on features of the binocular surface area in which it is embedded and is perceived as though it were treated as a binocular stimulus with regards to its visual direction and visual depth. PMID- 17337030 TI - Size effect in reactivity of copper nanoparticles to carbon tetrachloride degradation. AB - Surface area-normalized rate constants (k(SA)) of reaction between metallic nanoparticles and reducible contaminants, such as chlorinated hydrocarbons, heavy metals, and nitrate, have been reported to be dramatically increased as compared to that of commercial metallic powder. However, k(SA) for individual pollutants in previously published data vary by as much as 1-2 orders of magnitude and much of this variability is due to the effect of various sizes. The size dependence of the reactivity of nanoparticles is not yet fully understood; however, yielding nanoparticles with uniform size and without agglomeration during the period of reaction would demonstrate the effect of varying particle size. In this study, resin-supported zerovalent copper with average particle size of 7, 10, 18, 26, and 29, respectively, were successfully synthesized and evidenced no agglomeration during the reaction period of 10h. The k(SA) of copper nanoparticles (k(n,SA)) was 110-120 times higher than that of powdered copper particles (k(p,SA)) when the copper particle size was about 10nm. However, for diameters of 18-29 nm, the ratio of k(n,SA)/k(p,SA) was around 10-20, indicating that the reactivity of small copper nanoparticles (approximately 10nm) varies discontinuously. Thus, most variability in previous k(SA) is attributed to the presence of small nanoparticles. PMID- 17337031 TI - PAH removal from spiked municipal wastewater sewage sludge using biological, chemical and electrochemical treatments. AB - Polycyclic aromatic hydrocarbons (PAHs) have been widely studied due to their presence in all the environmental media and toxicity to life. These molecules are strongly adsorbed on the particulate matters of soils, sludges or sediments because of their strong hydrophobicity which makes them less bioavailability, thus limiting their bioremediation. Different sludge treatment processes were tested to evaluate their performances for PAH removal from sludge prealably doped with 11 PAHs (5.5mg each PAH kg(-1) of dry matter (DM)): two biological processes (mesophilic aerobic digestion (MAD) and simultaneous sewage sludge digestion and metal leaching (METIX-BS)) were tested to evaluate PAH biodegradation in sewage sludge. In parallel, two chemical processes (quite similar Fenton processes: chemical metal leaching (METIX-AC) and chemical stabilization (STABIOX)) and one electrochemical process (electrochemical stabilization (ELECSTAB)) were tested to measure PAH removal by these oxidative processes. Moreover, PAH solubilisation from sludge by addition of a nonionic surfactant Tween 80 (Tw80) was also tested. The best yields of PAH removal were obtained by MAD and METIX-BS with more than 95% 3-ring PAH removal after a 21-day treatment period. Tw80 addition during MAD treatment increased 4-ring PAHs removal rate. In addition, more than 45% of 3 ring PAHs were removed from sludge by METIX-AC and during ELECSTAB process were quiet good with approximately 62% of 3-ring PAHs removal. However, little weaker removal of 3-ring PAHs (<35%) by STABIOX. None of the tested processes were efficient for the elimination of high molecular weight (> or = 5-ring) PAHs from sludge. PMID- 17337032 TI - Investigation of triclosan fate and toxicity in continuous-flow activated sludge systems. AB - The purpose of this research was to study the fate and toxicity of triclosan (TCS) in activated sludge systems and to investigate the role of biodegradation and sorption on its removal. Two continuous-flow activated sludge systems were used; one system was used as a control, while the other received TCS concentrations equal to 0.5 and 2mgl(-1). At the end of the experiment, 1mgl(-1) TCS was added in the control system to investigate TCS behaviour and effects on non-acclimatized biomass. For all concentrations tested, more than 90% of the added TCS was removed during the activated sludge process. Determination of TCS in the dissolved and particulate phase and calculation of its mass flux revealed that TCS was mainly biodegraded. Activated sludge ability to biodegrade TCS depended on biomass acclimatization and resulted in a mean biodegradation of 97%. Experiments with batch and continuous-flow systems revealed that TCS is rapidly sorbed on the suspended solids and afterwards, direct biodegradation of sorbed TCS is performed. Regarding TCS effects on activated sludge process, addition of 0.5mgl(-1) TCS on non-acclimatized biomass initially deteriorated ammonia removal and nitrification capacity. After acclimatization of biomass, nitrification was fully recovered and further increase of TCS to 2mgl(-1) did not affect the performance of activated sludge system. The effect of TCS on organic substrate removal was minor for concentrations up to 2mgl(-1), indicating that heterotrophic microorganisms are less sensitive to TCS than nitrifiers. PMID- 17337033 TI - Alkane biodegradation and dynamics of phylogenetic subgroups of sulfate-reducing bacteria in an anoxic coastal marine sediment artificially contaminated with oil. AB - For 503 days, unoiled control and artificially oiled sediments were incubated in situ at 20m water depth in a Mediterranean coastal area. Degradation of the aliphatic fraction of the oil added was followed by GC-MS. At the same time, terminal restriction fragment length polymorphism (T-RFLP) of 16S rRNA encoding genes was used to detect dynamics in the sulfate-reducing bacteria (SRB) community in response to the oil contamination. Specific polymerase chain reaction (PCR) primer sets for five generic or suprageneric groups of SRB were used for PCR amplification of DNA extracted from sediments. During the experiment, hydrocarbons from C(17) to C(30) were significantly degraded even in strictly anoxic sediment layers. Of the five SRB groups, only two groups were detected in the sediments (control and oiled), namely the Desulfococcus Desulfonema-Desulfosarcina-like group and the Desulfovibrio-Desulfomicrobium-like group. Statistical analysis of community patterns revealed dynamic changes over time within these two groups following the contamination. Significant differences in community patterns were recorded in artificially oiled compared with control sediments. Cloning and sequencing of 16S rRNA encoding genes performed after 503 days showed that many of the most abundant sequences were closely related to hydrocarbonoclastic SRB which could have played an active role in the observed biodegradation of aliphatic hydrocarbons. Results from the present study provide useful information on the dynamics of dominant SRB in heavily oil-contaminated sediments and their potential for anaerobic biodegradation for the treatment of spilled oil in anoxic marine environments. PMID- 17337034 TI - Monitoring and identification of airborne asbestos in unorganized sectors, India. AB - Rajasthan state in India is credited to cater more than 90% of total production of asbestos in this country, of which around 60% is processed there in unorganized sectors including milling and manufacturing of asbestos-based products. Unorganized asbestos units particularly mills showed unhealthy occupational conditions, therefore industrial hygiene study was carried out focusing on the prevalence of asbestos fibres in air at work zone area of asbestos milling units. Fibre levels were in the range of 2.00-5.09f/cm(3) and 4.07-15.60f/cm(3) in unorganized asbestos mills of Rajasthan located at Beawer and Deogarh districts, respectively. Like asbestos concentration, fibre type and length are also vital factors in the health risk assessment of industrial workers. Phase contrast and polarized light microscopic study of asbestos fibres showed their amphibole nature registering about 90% as tremolite and rest as anthophyllite. Fibre length measured micrometrically were sub-grouped in <10microm, 11-20microm, 21-30microm and >30microm. About 30-40% fibres belonged to sub-group <10microm. It is concluded that unorganized asbestos mills bear poor industrial unhygienic conditions reflected specifically from their manyfold higher fibre concentrations than the Indian and International standards. Poor industrial unhygienic conditions are attributable to obsolete milling technology, lack of pollution control devices and escape from regulatory control. PMID- 17337035 TI - Effect of sulfate reduction activity on biological treatment of hexavalent chromium [Cr(VI)] contaminated electroplating wastewater under sulfate-rich condition. AB - Electroplating wastewater (EW) containing heavy metals was treated by a two-stage packed-bed reactor system. The EW was highly contaminated with hexavalent chromium and other heavy metals as well as sulfate because sulfuric acid had been mainly used to polish the surface of metals to be electroplated. This acidic EW was effectively neutralized in an alkaline reactor where limestone had been packed. The neutralized wastewater together with organic wastewater from a starch processing factory (SPW) was fed to a bioreactor packed with waste biomass. The SPW was used to supplement the electron donor in the sulfidogenic bioreactor. During the whole operation, we investigated the stoichiometry of electron to see what could be a major factor to remove Cr in the wastewater. The removal rates of sulfate and Cr(VI) were dependent on the consumption rate of organic materials in the wastewater. The stoichiometric studies also showed that about 63% of electrons from oxidation of organic materials were used to reduce sulfate. When the electrons of sulfide oxidation to elemental sulfur was at least 1.3 times higher than that of Cr(VI) reduction to Cr(III), Cr(VI) was completely removed. This result suggests that Cr(VI) reduction can be expected to take place under sulfate-rich anaerobic conditions, and sulfide produced by sulfate reducing bacteria could be used to immobilize soluble chromium through Cr(VI) reduction. PMID- 17337036 TI - Effect of recycle-to-influent ratio on activities of nitrifiers and denitrifiers in a combined UASB-activated sludge reactor system. AB - A laboratory study using a combined upflow anaerobic sludge bed (UASB)-activated sludge (AS) reactor system was undertaken to explore the effect of recycle-to influent ratio (R(e)=1, 2, and 3) on the activities of nitrifiers and denitrifiers. Suspended-solids pre-settled piggery wastewater was used as the substrate-feed wastewater. At the R(e) of 1-3, the combined reactor system achieved efficient removal of COD (96-97%), TKN (100%) and total nitrogen TN (54 77%). Methanogenesis occurred with nearly-complete denitrification in the UASB reactor, whereas complete nitrification took place in the AS reactor. A higher R(e) (i.e., accompanied with a shorter solids retention time) resulted in a larger amount of high-activity denitrifiers and thereby achieved a higher TN removal efficiency. Compact granules and a high biomass concentration in the UASB reactor were observed. At the R(e) of 1-3, the maximum specific reaction rate of nitrifiers (0.45-0.49 NH(4)(+)-NmgVSS(-1)d(-1)) and the specific nitrification rates of mixed culture (0.18-0.22mg NH(4)(+)-NmgVSS(-1)d(-1)) in the AS reactor varied slightly; whereas the maximum specific reaction rate of denitrifiers (0.18 0.27mg NO(x)(-)-NmgVSS(-1)d(-1)) and the specific denitrification and COD removal rates of mixed culture (0.025-0.050mg NO(x)(-)-NmgVSS(-1)d(-1); 0.24 0.31mgCODmgVSS(-1)d(-1)) in the UASB reactor increased with increasing R(e). The primary finding of the study is that the combined UASB-AS reactor system should be operated at a higher R(e) to maintain high-activity denitrifiers to remove organic materials and nitrogen from piggery wastewater. PMID- 17337037 TI - Vertebral morphology of Nacholapithecus kerioi based on KNM-BG 35250. AB - This paper describes the morphology of the vertebral remains of the KNM-BG 35250 Nacholapithecus kerioi individual from the Middle Miocene of Kenya. Cervical vertebrae are generally large relative to presumed body mass, suggesting a heavy head with large jaws and well-developed neck muscles. The atlas retains the lateral and posterior bridges over the vertebral artery. The axis has a robust dens and a large angle formed by superior articular surfaces. The thoracic vertebral specimens include the diaphragmatic vertebra and one post-diaphragmatic vertebra. The thoracic vertebral bodies are much smaller that those of male Papio cynocephalus, whereas many of the dorsal elements are large and robust, exceeding those of male P. cynocephalus. Lumbar vertebral bodies are small relative to body mass, craniocaudally moderately long, and have a median ventral keel. The transverse process is craniocaudally long and arises from the widest part of the body cranially and the pedicle above the inferior vertebral notch caudally. Anapophyses are present in one of the preserved lumbar vertebrae. The postzygapophyses are thick dorsoventrally. These lumbar features are broadly shared with Proconsul. However, the base of the spinous process is longer and more caudally positioned in N. kerioi compared to Proconsul, and is more similar to the condition in Pongo. They are not dorsally (or moderately caudally) directed as is seen in P. nyanzae, Pan, and most other extant primates. A caudally directed spinous process does not permit a broad range of spinal dorsiflexion. The presumed stiff back in N. kerioi suggests a different locomotor repertoire than in Proconsul. Morotopithecus bishopi, although not possessing the same features, exhibits another morphological suite of characters for lumbar stiffness. Diverse functional adaptations of the lumbar spine were present in African hominoids during the Early to Middle Miocene. PMID- 17337038 TI - Announcing a Still Bay industry at Sibudu Cave, South Africa. AB - Sibudu Cave in KwaZulu-Natal, South Africa, has a long Middle Stone Age (MSA) sequence with good organic preservation. The uppermost MSA sequence includes industries attributed to the final and late MSA and the Howiesons Poort. Below the Howiesons Poort are two layers containing some thin, bifacial lanceolate points, mostly in the form of distal and proximal fragments. These double-pointed foliates are the fossile directeur of the Still Bay Industry, and importantly, this Sibudu industry provides confirmation that the Still Bay predates the Howiesons Poort Industry. Technologically, the points from Sibudu are comparable to those from other South African sites with Still Bay occurrences (e.g., Blombos Cave and Hollow Rock Shelter). Although dating of the Sibudu Still Bay is preliminary, its age falls within the range of that at Blombos. For the past two decades, archaeologists have rejected the idea of a Still Bay Industry occurring outside of the Western Cape, but the Still Bay at Sibudu shows that this industry was, indeed, geographically widespread. PMID- 17337039 TI - Modern cognition in the absence of working memory: does the working memory account of Neandertal cognition work? PMID- 17337040 TI - Role of the T744C polymorphism of the P2Y12 gene on platelet response to a 600-mg loading dose of clopidogrel in 597 patients with non-ST-segment elevation acute coronary syndrome. AB - BACKGROUND: Variability in platelet response to clopidogrel and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. Recently, the T744C polymorphism of the P2Y12 receptor gene has been associated with enhanced platelet aggregation in healthy volunteers, suggesting a possible mechanism for modulation of clopidogrel response. AIM OF THIS STUDY: To assess whether the clopidogrel response may be influenced by the T744C P2Y12 gene polymorphism in patients with non ST elevation acute coronary syndrome (NSTE ACS). METHODS: 597 NSTE ACS patients were included in our study and were divided into 3 groups: CC homozygotes, CT heterozygotes ad TT homozygotes. All patients received loading doses of 600 mg clopidogrel and 250 mg aspirin at least 12 hours before blood samples. Clopidogrel response was assessed by post-treatment ADP 10 micromol/L-induced platelet aggregation (ADP-Ag), VASP phosphorylation (PRI VASP) and P-selectin expression (PS). Clopidogrel resistance was defined by persistence of High Post-treatment Platelet Reactivity (HPPR=ADP-Ag>70%). RESULTS: Significant variability in the distribution of platelet parameters was observed in the overall study population. No significant difference in platelet parameter profiles was observed within patients having the same genotype, for ADP-Ag (p=0.39), PRI VASP (p=0.97) and PS (p=0.62). The genotype frequencies of the T744C polymorphism of the P2Y12 gene were similar in responders and non responders defining by HPPR (p=0.75). CONCLUSION: Our study did not show any influence of the T744C polymorphism of the P2Y12 receptor gene on clopidogrel response assessed by ADP-Ag, PRI VASP or P-selectin expression in NSTE ACS patients. PMID- 17337041 TI - Relationship between changes in platelet reactivity and changes in platelet receptor expression induced by physical exercise. AB - INTRODUCTION: In previous studies we have consistently shown a significant increase of platelet reactivity after exercise in patients with obstructive coronary artery disease (CAD). We also observed a significant individual variability in the response to exercise of platelet reactivity in these patients. Whether exercise-induced changes in platelet reactivity correlate with changes in platelet membrane receptors in patients with CAD is unknown. METHODS: We studied 26 patients with stable CAD and 10 matched healthy controls who underwent a symptom-limited treadmill exercise stress test. Venous blood samples were collected at rest and within 5 min of peak exercise. Platelet reactivity was measured by the PFA-100 method as time to occlude (closure time, CT) a ring coated with collagen/adenosine diphosphate (C/ADP). Platelet expression of glycoprotein (GP) IIb/IIIa, in both global (CD41) and active form (PAC-1), and P selectin (CD62P) and formation of leukocyte-platelet aggregates were assessed by flow cytometry. RESULTS: After exercise CT did not change in controls (85.4+/-12 to 84.0+/-9 s, p=0.37), whereas it decreased in CAD patients (98.8+/-24 to 91.4+/ 25 s, p<0.001). After exercise, CD41 and PAC-1 platelet expression increased significantly in CAD patients (p=0.04 for both), but not in controls (p=0.39 and p=0.98, respectively). To evaluate the relationship between the response to exercise of platelet reactivity and of platelet receptor expression, CAD patients were divided into two groups: CAD group 1 (16 patients, decrease in CT >5 s after exercise) and CAD group 2 (10 patients no increase in platelet reactivity after exercise). CD41 and PAC-1 expression increased in CAD group 1 (p=0.008 and p=0.026, respectively) but not in CAD group 2 (p=0.39 and p=0.50, respectively). No significant differences were observed between the 2 groups for changes in CD62P and leukocyte-platelet aggregates. CONCLUSIONS: Our data show that, in patients with stable CAD, an increased platelet reactivity to C/ADP stimulation after exercise, as assessed by the PFA-100 method, is specifically associated with an increased expression of platelet GP IIb/IIIa receptor. PMID- 17337043 TI - Fructosamine 3-kinase and other enzymes involved in protein deglycation. PMID- 17337042 TI - Receptor tyrosine kinase-G-protein coupled receptor complex signaling in mammalian cells. PMID- 17337044 TI - Physical activity levels of children in special schools. AB - OBJECTIVE: Children's physical activity (PA) has been studied extensively, but little information is available on those with disabilities. We sought to examine the PA of children with disabilities during physical education (PE) and recess while simultaneously documenting environmental conditions. METHOD: Five schools designed for students with four types of special needs (physical disability, mild intellectual disability, hearing impairment, and visual impairment) participated. We used the System for Observing Fitness Instruction Time (SOFIT) to code the PA of children in grades 4 to 6 during both PE and recess and to document teacher behavior and lesson context in PE. Observations were conducted during 2 school days over a 2-week period. RESULTS: Children accrued little moderate-to-vigorous physical activity (MVPA) during PE (7.8 min) and recess (8.9 min). Activity levels varied across disability types, with differences attributed to lesson context and teacher behavior. Children with physical disabilities were the least active during both PE and recess. CONCLUSIONS: Children with disabilities accrue little PA at school. Increased PE frequency and lesson intensity, more PA opportunities during non-structured school time, and collaborations with home and community agencies are needed to reach PA recommendations. PMID- 17337045 TI - Decrease in glutathione (GSH) content in bovine sperm after cryopreservation: comparison between two extenders. AB - Growing evidence suggests that among the causes which deteriorate qualitative and functional characteristics of semen after freezing and thawing, there are those linked to oxidative stress and decrease detoxification of antioxidants present in the cells and seminal plasma. Overall, cryopreservation reduces the spermatozoal GSH content. In the present study we assessed the motility, capacitation status, ability to undergo acrosome reaction and levels of GSH in bovine spermatozoa after freezing and thawing, and compared the effects of the egg yolk tris-citrate and a commercial extenders (Bioxcell). Six semen samples were collected from each of five bulls and frozen and thawed in the two extenders. The level of total GSH of bovine spermatozoa detected in the raw semen ranged from 246.5 to 776.2 pmoles/mg of protein. The Bioxcell extender was superior in preserving GSH content (647.2+/-300.1 versus 223.6+/-154.0 pmoles/mL; P<0.05), motility levels (44.3+/-4.8 versus 41.8+/-4.0%; P<0.05), non-capacitated state (68.3+/-13.6 versus 61.3+/-17%; P<0.05) and a lower proportion of acrosome reacted spermatozoa post thaw (3.8+/-2.1 versus 6.3+/-3.1%; P<0.001) compared to egg yolk tris citrate extender. These findings could be partially ascribed to the high GSH level contained in the commercial extender which seem able to alleviate oxidative damages to spermatozoa surviving freezing thawing procedures. Further researches are required in order to validate in vivo these results. PMID- 17337046 TI - Brief report: perceptions of positive and negative support: do they differ for pregnant/parenting adolescents and nonpregnant, nonparenting adolescents? AB - This study was designed to examine perceptions of type, source, and amount of social support reported by pregnant and/or parenting (PP) and nonpregnant, nonparenting (NPNP) adolescents. Greater support generally was reported by NPNP than by PP adolescents. The groups did not differ with respect to their perceptions of types of support reported on either the Inventory of Socially Supportive Behaviors (ISSB) or the Arizona Social Support Interview Schedule (ASSIS). PP adolescents reported more support from teachers on the ASSIS than did NPNP adolescents. NPNP adolescents reported more support from best friends and sisters than did the PP group. PMID- 17337047 TI - In vitro lifetime of dental ceramics under cyclic loading in water. AB - All-ceramic dental restorations exhibit enhanced esthetics and biocompatibility as compared to traditional metal-based prosthesis. However, long-term fatigue and subcritical crack growth in the presence of water and cyclic loading can decrease the strength of ceramic components over time. We investigated the cyclic fatigue in water of three dental materials currently used as frameworks in all-ceramic restorations: a 3 mol%-yttria partially stabilized zirconia (3Y-TZP, Cercon, Degudent GmbH), a Al(2)O(3)-ZrO(2)-Glass composite (Inceram-Zirconia, Vita Zahnfabrik GmbH) and a Li(2)O.2SiO(2) glass ceramic (Empress 2, Ivoclar Vivadent AG). Fatigue and fast fracture tests were performed to determine the Weibull distribution of lifetime and initial mechanical strength for each framework component. In spite of its noticeable susceptibility to fatigue in water, the 3Y TZP material was found to be particularly suitable for the preparation of posterior all-ceramic bridges due to its high initial mechanical strength. Guidelines are provided for the selection of materials and the design of all ceramic posterior bridges exhibiting lifetime longer than 20 years under severe wet and cyclic loading conditions. PMID- 17337048 TI - Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization. AB - Biodegradable synthetic matrices that resemble the size scale, architecture and mechanical properties of the native extracellular matrix (ECM) can be fabricated through electrospinning. Tubular conduits may also be fabricated with properties appropriate for vascular tissue engineering. Achieving substantial cellular infiltration within the electrospun matrix in vitro remains time consuming and challenging. This difficulty was overcome by electrospraying smooth muscle cells (SMCs) concurrently with electrospinning of a biodegradable, elastomeric poly(ester urethane) urea (PEUU) small-diameter conduit. Constructs were cultured statically or in spinner flasks. Hematoxylin and eosin (H&E) staining demonstrated qualitatively uniform SMCs integration radially and circumferentially within the conduit after initial static culture. In comparison with static culture, samples cultured in spinner flasks indicated 2.4 times more viable cells present from MTT and significantly larger numbers of SMCs spread within the electrospun fiber networks by H&E image analysis. Conduits were strong and flexible with mechanical behaviors that mimicked those of native arteries, including static compliance of 1.6+/-0.5 x 10(-3)mmHg(-1), dynamic compliance of 8.7+/-1.8 x 10(-4)mmHg(-1), burst strengths of 1750+/-220 mmHg, and suture retention. This method to rapidly and efficiently integrate cells into a strong, compliant biodegradable tubular matrix represents a significant achievement as a tissue engineering approach for blood vessel replacement. PMID- 17337049 TI - Protein complexed with chondroitin sulfate in poly(lactide-co-glycolide) microspheres. AB - Chondroitin sulfate (CsA) is an acidic mucopolysaccharide, which is able to form ionic complexes with positively charged proteins. In this study, a protein-CsA complex was constructed to nano-sized particles. Zeta potential measurements revealed that a CsA-to-protein fraction of greater than 0.1 results in a neutralization of the positive charge on lysozyme (Lys). Based on this preliminary study, we have prepared poly(lactide-co-glycolide) (PLGA) microspheres harboring Lys/CsA complexes via the multi-emulsion method. Protein stability in the PLGA microspheres was preserved during both microsphere preparation and protein release. The profiles of Lys release from the PLGA microspheres evidenced nearly zero-order kinetics, depending on the quantity of CsA. An in vivo fluorescent image of experimental mouse tissue showed that the PLGA microspheres with the Lys/CsA complex had released the entirety of their Lys without no residual amount after 23 days, but microspheres without the complex harbored a great deal of residual Lys, which is attributable to its degradation by acidic PLGA degradates. The tissue reaction evidenced by the PLGA microspheres stabilized with CsA showed minimal foreign body reaction and little configuration of immune cells including neutrophils and macrophages, but the reactions of the PLGA microspheres without CsA were characterized by a relatively elevated inflammation. These results show that CsA is a viable candidate for long-acting micro-particular protein delivery. PMID- 17337050 TI - 2005 Trophoblast Research Award Lecture: Defects in the keratin cytoskeleton disrupt normal murine placental development and trophoblast cell function. AB - The keratin cytoskeleton is present in all trophoblast cell subtypes of the mouse and human placenta and is required to maintain the structural integrity of these cells. Recently, various genetic mouse models have shown that a normal keratin network is necessary for placental development. Keratin-deficiency leads to trophoblast giant cell fragility, breaking the barrier between the conceptus and the maternal blood circulation. Alternatively, keratin aggregation prevents chorioallantoic attachment, a key developmental milestone required for the formation of the labyrinth within the mouse placenta. These models give us insight into cytokeratin function in human trophoblast cell subtypes and suggest that defects in the keratin cytoskeleton may result in intrauterine growth restriction or miscarriage. PMID- 17337051 TI - NQO1*2 polymorphism and response to treatment in patients with multiple myeloma. PMID- 17337052 TI - Expression of immune-related genes in the oyster Crassostrea gigas during ontogenesis. AB - The work presented here reports the expression of immune-related genes during ontogenesis in the oyster Crassostrea gigas. Expression patterns of 18 selected genes showed that RNAs detected in oocytes and 2-4 cell embryos are of maternal origin and that gene transcription starts early after fertilization. The expression patterns of 4 genes (Cg-timp, Cg-tal, Cg-EcSOD and Drac3) suggested that hemocytes appear in the gastrula-trochophore stages. The localization of Cg tal expression suggested that hematopoietic cells were derived from vessels and/or artery endothelia cells. Moreover, a bacterial challenge affected the level of expression of genes. Indeed, a change in expression levels was observed for Cg-LBP/BPI, Cg-timp, Drac3 and Cg-MyD88 genes in larval stages upon exposure to non-pathogenic bacteria. In early juveniles, a modulation was also observed for Cg-LBP/BPI, Cg-timp, Cg-MyD88 and for Cg-tal, according to the concentration of bacteria. Altogether, the results showed that studying the appearance of immunocompetent cells through their ability to express immune-related genes is a tool to gain insight the ontogenesis of the oyster immune system. PMID- 17337053 TI - Proteolytic activation of pro-spatzle is required for the induced transcription of antimicrobial peptide genes in lepidopteran insects. AB - Microbial infection leads to proteolytic activation of Drosophila spatzle, which binds to the toll receptor and induces the synthesis of immune proteins. To test whether or not this mechanism exists in lepidopteran insects, we cloned the cDNA of Bombyx mori spatzle-1 and overexpressed the full-length and truncated BmSpz1 cDNA in Escherichia coli. The insoluble fusion proteins were affinity-purified under denaturing condition. After the silkworm larvae were injected with renatured BmSpz1, mRNA levels of antimicrobial peptide genes greatly increased. Similar transcriptional up-regulation was also found in Manduca sexta. Injection of pro-BmSpz1 had no such effect. When pro-BmSpz1 and Micrococcus luteus were incubated with the plasma from M. sexta larvae, we detected proteolytic processing of pro-BmSpz1. These results suggest that active spatzle is required for the induced production of antimicrobial peptides in B. mori and M. sexta. PMID- 17337054 TI - Molecular characterization of lentiviruses from goats from Poland based on gag gene sequence analysis. AB - Caprine arthritis-encephalitis virus (CAEV) infection in goats is worldwide but with higher prevalence in industrialized countries. While positive serology of CAEV in Polish goats was reported there was no genetic study of this virus. In this study, we described the molecular characterization of lentiviruses isolated from seropositive goats from Poland. We cloned and sequenced a fragment from the gag gene covering part of the coding sequences for the matrix (MA) p17 and for the capsid (CA) p25 proteins. Resulting nucleotide sequences were aligned with those from other ovine/caprine lentivirus isolates. We present data showing that the sequences of most goat lentivirus isolates are closer to the prototypic CAEV Co isolate, nevertheless from one goat we isolated a virus that is closer to the sheep Maedi Visna virus (MVV) isolate. This might indicate a recent cross-species infection from sheep to goat. PMID- 17337055 TI - Two specific sites for binding of K88ab Escherichia coli fimbriae to porcine intestinal brush border membranes. AB - We have studied the characteristics of the binding of the K88ab Escherichia coli fimbrial antigen to porcine brush border membranes by solid phase binding assay. Binding of biotinylated K88ab to brush border membranes followed a sigmoidal dependence and was saturable, apparent saturation occurring with 0.8 ng of fimbriae (approx. 7 ng of fimbriae per microg of brush border protein) irrespective of incubation temperature in the range of room temperature to 4 degrees C. A Hill plot of log [(fimbriae bound)/(maximal binding-fimbriae bound)] vs. log free fimbriae gave a maximal slope of about 2, indicating the existence of two binding sites. From an analysis of an Scatchard plot, apparent binding constants (1)K(2) and (2)K(2) of 7.1 x 10(8) and 17.1 x 10(8)M(-1) were obtained at room temperature. Nor did temperature have any effect on the rate of binding or on receptor affinity (S(0.5)). PMID- 17337056 TI - Prion protein activates and fixes complement directly via the classical pathway: implications for the mechanism of scrapie agent propagation in lymphoid tissue. AB - C1q-deficient and complement depleted mice are highly resistant to intraperitoneal scrapie infection. The molecular mechanisms of complement involvement in scrapie pathogenesis remain unclear. Previous detailed studies have indicated mouse prion protein interactions with human C1q but the question of subsequent complement activation has remained unaddressed. In this investigation, murine prion protein, both recombinant and also from diseased tissue sources, directly activated and fixed complement via the classical but not the alternative pathway. The importance of complexed cupric ions was observed. In addition, evidence of IgG-independent C4 fixation by prion proteins was also shown. Surface plasmon resonance binding studies using variously clustered immobilized recombinant mouse prion protein indicated strong interactions with both purified mouse C1q and also mouse Factor H. Binding, especially by C1q, was dependent upon the volume of immobilized prion protein, suggesting a threshold of clustering density required to support strong interactions. Furthermore, clustered immobilized prion protein appeared capable of promoting polymerization of soluble-phase monomeric prion protein. Direct covalent attachment of complement components to prion proteins via classical pathway activation illustrates a potential mechanism underpinning their trafficking to, and subsequent propagation within, lymphoid tissues. PMID- 17337057 TI - Porcine differential gene expression in response to Salmonella enterica serovars Choleraesuis and Typhimurium. AB - An investigation of the porcine response to gastrointestinal infection with Salmonella enterica serovars Choleraesuis (narrow host range) and Typhimurium (broad host range) revealed markedly different transcriptional profiles. Seven genes identified by suppression subtractive hybridization as up-regulated in the mesenteric lymph nodes at 24h (h) post-inoculation (p.i.) in serovar Choleraesuis infected pigs (ARPC2, CCT7, HSPH1, LCP1, PTMA, SDCBP, VCP) and three genes in serovar Typhimurium-infected pigs (CD47/IAP, CXCL10, SCARB2) were analyzed by real-time PCR at 8h, 24 h, 48 h, 7 days (d) and 21 d p.i. A comparison between the two Salmonella infections revealed significant differences in transcriptional induction early in the infection (8-24h) for the serovar Typhimurium-infected pigs, whereas the serovar Choleraesuis-infected pigs exhibited significantly higher levels of gene expression at the later time points (48h-21 d), except for HSPH1. A similar gene expression trend was observed for immune-related genes involved in innate immunity and the inflammatory T helper 1 (Th1) response. Initial repression of gene expression in the serovar Choleraesuis-infected pigs from 8 to 48h p.i. (IFNG, IL12A, IL4, IL8, CSF2) coincided with extended transcriptional activation throughout the 21 d infection (IFNG, INDO, SOCS1, STAT1, IL1B, IL6, IL8, SLC11A1). The serovar Typhimurium-infected swine presented a more transient induction of immune-related genes (IFNG, INDO, IRF1, SOCS1, STAT1, IL1B, IL8, SLC11A1) early in the infection (24-48 h) followed by a significant repression of IL12A, IL12B, IL4, IL8 and CSF2. Collectively, these data reveal specific porcine genes with differences in gene expression kinetics that may be responsible for the variation in disease progression observed in swine infected with Typhimurium compared to Choleraesuis. PMID- 17337058 TI - Prostacyclin production is not controlled by prostacyclin synthase but by cyclooxygenase-2 in a human follicular dendritic cell line, HK. AB - We have recently demonstrated that human follicular dendritic cells (FDCs) strongly express prostacyclin synthase. The purpose of this study is to investigate the production mechanism of prostacyclin using the established human FDC line, HK. The levels of PGIS protein expression did not vary during the different stages of the cell cycle. We stimulated HK cells with various inflammatory cytokines but, none of the tested stimuli modulated PGIS expression significantly. However, incubation of HK cells with tumor necrosis factor (TNF) alpha gave rise to a significant increase in the protein level of cyclooxygenase (COX)-2. Furthermore, elevated levels of prostacyclin secretion stimulated by TNF alpha were markedly down-regulated by indomethacin and a selective COX-2 inhibitor. These results suggest that the production of prostacyclin in FDC is controlled by the regulation of upstream COX-2 but not by terminal PGIS protein production. This study has important implications for the development of new anti inflammatory drugs. PMID- 17337060 TI - Correlation of visual acuity with foveal hypoplasia grading by optical coherence tomography in albinism. AB - PURPOSE: To develop a new foveal hypoplasia grading system using optical coherence tomography (OCT) and to determine the correlations of visual acuity to the iris transillumination, macular transparency, and foveal hypoplasia grades, respectively, in young albinism patients. DESIGN: Observational case series. PARTICIPANTS: Thirteen patients who were clinically diagnosed with oculocutaneous albinism. METHODS: The authors obtained refraction and correction for participants, who then underwent anterior segment photography and fundus photography. Foveal hypoplasia was evaluated using a fast macular cross-hair scan with StratusOCT (Carl Zeiss Meditec, Dublin, CA). The authors developed a new grading system based on foveal hyporeflectivity, the degree of choroidal transillumination, the presence of the tram-tract sign, and foveal depression as determined from OCT images. Correlations of Snellen visual acuity to the iris transillumination, macular transparency, and foveal hypoplasia grades were calculated, and areas under receiver operating characteristic curves (AROCs) were measured to evaluate the predictive value of foveal hypoplasia grading using OCT. MAIN OUTCOME MEASURES: The AROCs of foveal hypoplasia grading by OCT. RESULTS: Thirteen patients were enrolled. Correlations of visual acuity to the iris transillumination (P<0.001), macular transparency (P = 0.014), and foveal hypoplasia (P = 0.004) grades were significant. The AROC values for foveal hypoplasia measurement by OCT, iris transillumination, and macular transparency measurements were 0.98, 0.91, and 0.87, respectively. CONCLUSIONS: The prognostic value of foveal hypoplasia as assessed by OCT in young patients with albinism is superior to grades based on iris transillumination or macular transparency. PMID- 17337059 TI - Characterization of the sequence and architectural constraints of the regulatory and core regions of the human interleukin-2 promoter. AB - The cytokine interleukin-2 (IL-2) is produced by T cells when they recognize a foreign antigen. Transcription of the IL-2 gene is tightly controlled by the combined actions of multiple transcriptional activators. However, the contribution of sequences in the IL-2 core promoter and the architecture of the IL-2 regulatory region to setting levels of IL-2 transcription are not understood. We have probed these properties of the human IL-2 promoter to understand how the regulatory and core promoter regions cooperate in response to T cell stimulation, thereby setting high levels of inducible transcription. We found that the IL-2 core promoter contains a TATA box that is critical for inducible expression. Moreover, the spacing and orientation between the IL-2 regulatory and core promoter regions is important for setting the level of transcription. The regulatory region of the IL-2 promoter is capable of mediating high levels of expression even when the helical phasing between transcription factor binding sites is perturbed. Although long considered an enhancer, our studies indicate that the regulatory region in the IL-2 promoter is better considered as a proximal regulatory element, since it lacks multiple properties associated with enhancer elements. PMID- 17337061 TI - Orbital Langerhans cell histiocytosis in adults. AB - PURPOSE: To report 3 patients with adult-onset orbital Langerhans cell histiocytosis (LCH). DESIGN: Retrospective interventional case reports. PARTICIPANTS: Three adult patients with orbital LCH. METHODS: Case reports from 2 different clinics and review of the scientific literature. MAIN OUTCOME MEASURES: Clinical course and radiologic and histologic findings. RESULTS: Three healthy patients, aged 20 to 36 (mean, 27) years, presented with biopsy-proven unilateral orbital LCH. The initial presenting complaints were mainly orbital pain and headache with or without orbital swelling and minimal effect on ocular movements. There was radiologic evidence of disease centered on the greater wing of sphenoid bone in all cases. Biopsy via lateral canthotomy was performed with LCH confirmed based on histologic and immunohistochemical findings. There was no evidence of disease elsewhere on systemic investigations. One patient had curettage and intralesional corticosteroids, 1 patient had a craniotomy for more complete resection of the lesion, and the third patient was referred for radiotherapy. All patients achieved complete resolution of symptoms and signs. None of the patients demonstrated any evidence of distant or recurrent disease at follow-up. CONCLUSIONS: Orbital LCH in adults is a rare, usually unifocal, and relatively benign disease most commonly affecting the greater wing of sphenoid bone, where there is still active bone marrow in young adults. There is no consensus on cause or therapy, but our reported cases show that several treatment modalities are effective. PMID- 17337062 TI - Cataract blindness in 4 regions of Guatemala: results of a population-based survey. AB - OBJECTIVE: To assess prevalence of visual impairment resulting from cataract and cataract surgical services in 4 departments (provinces) of Guatemala to facilitate further health care planning. DESIGN: Cross-sectional study. PARTICIPANTS: Ninety-eight enumeration areas were selected by systematic sampling in 4 departments in southwest Guatemala, with a combined population of 1,339,508 (2002 census). Ninety-eight clusters of 50 persons > or =50 years of age (4900 eligible persons) were selected by random walk, 1 in each selected enumeration area. A total of 4806 persons were examined (coverage, 98.1%): 1808 (37.6%) men and 2998 (62.4%) women. Mean age was 63.7 years. METHODS: Each eligible participant was interviewed and underwent an assessment of visual acuity and ophthalmic examination to assess lens status. MAIN OUTCOME MEASURES: Visual acuity of each eye with available correction and with pinhole correction; lens status; cause of visual impairment in 1 or both eyes; reason(s) why cataract operation had not been performed; and details of previous cataract surgery. RESULTS: Cataract is the major cause of bilateral blindness (66.1%). The adjusted prevalence of bilateral cataract blindness (best-corrected visual acuity [BCVA], <20/400) in people 50 years of age and older was 2.3% (95% confidence interval [CI], 1.8%-3.0%), or an estimated 3726 persons. The cataract surgical coverage was 49% for men and 28% for women. The adjusted prevalence of bilateral cataract and BCVA<20/200 in persons 50 years of age and older was 3.7% (95% CI, 2.9% 4.4%), or an estimated 5887 persons. In this last group, the surgical coverage was 29% (persons) and 19% (eyes). Of all operated eyes, 36% could not see 20/200. Being unaware of cataract (68%), inability to afford the procedure (12%), and fear of the procedure (10%) were mentioned most often as the reason why surgery had not been performed. CONCLUSIONS: There is a backlog in unoperated cataract in the survey area that will increase with ageing. Awareness campaigns, reducing cost, improving the outcome of cataract surgery, and expansion of surgical services may help to increase the cataract surgical rate. Women should be offered more cataract surgery. These results will enable health managers to plan effective interventions in line with Vision 2020. PMID- 17337063 TI - Cigarette smoking and age-related macular degeneration in the EUREYE Study. AB - OBJECTIVE: To examine the association between cigarette smoking and age-related maculopathy (ARM) including age-related macular degeneration (AMD) in the European population. DESIGN: Cross-sectional study. PARTICIPANTS: Four thousand seven hundred fifty randomly sampled > or =65-year-olds from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain). METHODS: Participants underwent an eye examination and digital retinal photography. The images were graded at a single center. Smoking history was ascertained by a structured questionnaire administered by trained fieldworkers. Multinomial and binary logistic regressions were used to examine the association between smoking history and ARM grade and type of AMD, taking account of potential confounders and the multicenter study design. MAIN OUTCOME MEASURES: Photographic images were graded according to the International Classification System for ARM and stratified using the Rotterdam staging system into 5 exclusive stages (ARM 0-3 and ARM 4, also known as AMD). Age-related macular degeneration also was classified as neovascular AMD or geographic atrophy (GA). RESULTS: One hundred fifty-eight cases were categorized as AMD (109 neovascular AMD and 49 GA); 2260 had no signs of ARM (ARM 0). Current smokers had increased odds of neovascular AMD (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.4-4.8) or GA (OR, 4.8; 95% CI, 2.1-11.1), whereas for ex-smokers the odds were around 1.7. Compared with people with unilateral AMD, those with bilateral AMD were more likely to have a history of heavy smoking in the previous 25 years (OR, 5.1; 95% CI, 1.3-20.0). The attributable fraction for AMD due to smoking was 27% (95% CI, 19%-33%). There was no consistent association with ARM grades 1 to 3 and smoking. CONCLUSIONS: These findings highlight the need for increasing public awareness of the risks associated with smoking and the benefit of quitting smoking. Patients with unilateral disease who are current smokers should be advised of the risk of second-eye disease. PMID- 17337064 TI - Outcomes of wavefront-optimized surface ablation. AB - PURPOSE: To compare early visual outcomes after wavefront-optimized advanced surface ablation (ASA) with those after wavefront-optimized LASIK. DESIGN: Retrospective comparative series. PARTICIPANTS: One hundred thirty-six eyes undergoing ASA and 136 preoperative refraction-matched eyes undergoing LASIK from June 2004 through October 2005. METHODS: Database review of preoperative characteristics, including patient age, gender, refraction, and central corneal pachymetry; perioperative information, including type of surgery, flap thickness (for LASIK cases), ablation depth, and residual stromal bed thickness; and postoperative information, including uncorrected visual acuity (UCVA) at 1 day, 1 week, 2 weeks, and 3 months, refraction at 3 months, and complications. All ASA patients had topical mitomycin C applied intraoperatively. MAIN OUTCOMES MEASURES: Postoperative UCVA, best spectacle-corrected visual acuity (BSCVA), spherical equivalent (SE) refraction, speed of visual recovery, and postoperative complications. RESULTS: Surface ablation patients were younger (35.4 years vs. 39.8 years, P = 0.0002) and had thinner corneas (514 microm vs. 549 microm, P<0.0001) preoperatively. Average UCVA was significantly better after LASIK at 1 day (20/26.8 vs. 20/50.4, P<0.0001) and 2 weeks (20/24.4 vs. 20/33.3, P = 0.0002) postoperatively. However, by 3 months postoperatively, UCVA was better after ASA (20/20.8 vs. 20/22.7, P = 0.05), and 81.5% of patients achieved 20/20 or better UCVA after ASA, compared with 70.5% after LASIK (P = 0.05). More ASA eyes had postoperative UCVA that achieved or surpassed preoperative BSCVA than LASIK eyes (66% vs. 41.6%, P<0.0001). There were 53 patients who underwent bilateral simultaneous ASA. By 1 week, 87.5% had 20/40 or better UCVA in at least one eye and 62.5% had 20/40 or better UCVA in both eyes. By 2 weeks, 86.8% had 20/40 or better UCVA in one eye and 82.6% had 20/40 or better UCVA in both eyes. CONCLUSION: Initial visual recovery is more rapid after LASIK; however, by 3 months postoperatively UCVA and SE refractions were better after ASA. Advanced surface ablation is an effective alternative to LASIK, and based on early visual recovery, bilateral simultaneous surface ablation is a reasonable alternative to sequential surgery for the majority of patients. PMID- 17337065 TI - Incidence of cataract and outcomes after cataract surgery in the first 5 years after iodine 125 brachytherapy in the Collaborative Ocular Melanoma Study: COMS Report No. 27. AB - PURPOSE: To evaluate the effect of the radiation dose to the lens on cataract formation and effect of cataract surgery on visual acuity (VA) among patients with choroidal melanoma treated with iodine 125 (I125) brachytherapy. DESIGN: Prospective study of patients enrolled in one arm of a randomized clinical trial. PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) who received I125 brachytherapy as randomly assigned and also were phakic, with no history of cataract in the study eye at the time of enrollment (n = 532). METHODS: Each follow-up examination included an interim ocular history and full ophthalmic examination. Lens status (phakic, pseudophakic, or aphakic) and best corrected VA were recorded. For the purpose of this analysis, the date of the first examination at which an eye was reported to be aphakic or pseudophakic, to have vision-limiting lenticular opacities, or to have had cataract surgery was defined as the observed time of cataract development. Date of cataract surgery was defined as the date of the first follow-up examination at which cataract surgery was reported. MAIN OUTCOME MEASURES: Incidence of cataract and outcomes after cataract surgery. RESULTS: During the first 5 years of follow-up, cataracts developed in 362 (68%) of the 532 study eyes, including 49 (9%) that had had cataract surgery. By 5 years, 83% of study eyes were reported to have a cataract (95% confidence interval [CI], 79%-87%), and 12% had undergone cataract surgery (CI, 9%-15%) in the study eye. Eighteen percent of eyes that received a dose of 24 Gy or higher to the lens underwent cataract surgery, whereas only 4% of patients with <12 Gy to the lens underwent cataract surgery. Median VAs were 20/125 before cataract surgery and 20/50 after cataract surgery. After cataract surgery, VA improved by 2 lines or more in 32 (66%) patients and remained stable in 13 (26%) patients. The most common cause of lack of visual improvement after cataract surgery was presence of radiation retinopathy. CONCLUSION: Although cataract surgery was infrequent among COMS patients, VA remained stable or improved in the majority of these eyes after cataract surgery. PMID- 17337066 TI - Low-dose cyclophosphamide and interferon alfa 2a for the treatment of capillary hemangioma of the orbit. AB - PURPOSE: To report the use of a combination of low-dose cyclophosphamide and interferon alfa 2a (IFNalpha2a) for the treatment of orbital juvenile capillary hemangioma. DESIGN: Retrospective case series. PARTICIPANTS: Five patients with juvenile capillary hemangiomas of the orbit. METHODS: Five patients with a median age of 9 weeks presented with a rapidly enlarging orbital mass. Two patients also had involvement of the upper eyelid obstructing the visual axis. Patients underwent biopsy to confirm the diagnosis before starting combination therapy with low-dose oral cyclophosphamide (10 mg/kg per day for 3 days repeated every 2 weeks) and subcutaneous IFNalpha2a (3 million units/m2 per day once daily) for a maximum treatment time of 4 to 6 months. Patients underwent serial ophthalmic, hematologic, and neurologic evaluations. MAIN OUTCOME MEASURE: Regression of lesions after combination therapy. RESULTS: Four of 5 patients had marked regression of the hemangioma by 40% to 60% with subsequent reduction in proptosis, corneal exposure, and obstruction of the visual axis. None of the 4 patients developed amblyopia. Side effects included mild neutropenia and uncomplicated infections. There was no neurologic toxicity after a median follow up of 10 months. One patient failed to respond to treatment and required further treatment with intralesional steroid injections. CONCLUSIONS: Combination of low dose cyclophosphamide with IFNalpha2a for a short period of time induced early and lasting regression of orbital juvenile capillary hemangiomas with minimal side effects. This regimen may be a suitable alternative that avoids the toxicity of long-term administration of interferon only. However, the experience reported here does not show if cyclophosphamide alone may be sufficient and allow complete avoidance of interferon and its potential serious side effects, and longer follow up is needed to determine if cyclophosphamide causes any long-term harm. PMID- 17337067 TI - Psychosocial impairment associated with bipolar II disorder. AB - BACKGROUND: Significant research has looked at the psychosocial impairment associated with bipolar I disorder and major depressive disorder. Far less is known about the impact of bipolar II disorder. The present study assessed the social and work impairment associated with bipolar II disorder and whether these are more or less severe than those associated with bipolar I disorder or major depressive disorder. METHODS: Psychiatric outpatients with bipolar II disorder (n=89), bipolar I disorder (n=45) and major depressive disorder (n=1251) were assessed cross-sectionally by highly trained raters using semi-structured interviews. Participants were in a major depressive episode. Groups were compared on a series of indicators of psychosocial functioning. RESULTS: Bipolar I and II disorder were associated with greater absenteeism from work due to psychopathology compared to major depressive disorder. The bipolar disorders also had higher rates of hospitalization and suicide attempts. Bipolar II disorder had fewer hospitalization than bipolar I disorder which may have led to slightly less severe work impairment. Both conditions had similar rates of serious suicide attempts. LIMITATIONS: The study was cross-sectional and retrospective. Furthermore, the sample consisted of outpatients seeking treatment, limiting generalizability to other settings. CONCLUSION: Bipolar II disorder is associated with serious work impairment and a high number of serious suicide attempts. The level of impairment is more similar than it is different from that associated with bipolar I disorder. Clinicians would be mistaken to presume that the "softer" bipolar spectrum, specifically bipolar II disorder, is less impairing than bipolar I disorder. PMID- 17337068 TI - Antiepileptic drugs in migraine: from clinical aspects to cellular mechanisms. AB - Migraine and epilepsy share several clinical features, and epilepsy is a comorbid condition of migraine. Clinical studies have shown that some antiepileptic drugs are effective at preventing migraine attacks. A rationale for their use in migraine prophylaxis is the hypothesis that migraine and epilepsy share several common pathogenetic mechanisms. An imbalance between excitatory glutamate mediated transmission and GABA-mediated inhibition in specific brain areas has been postulated in these two pathological conditions. Moreover, abnormal activation of voltage-operated ionic channels has been implicated in both migraine and epilepsy. Cortical spreading depression has been found to be involved in the pathophysiology of epilepsy, in addition to the generation of migraine aura. PMID- 17337069 TI - DNA abrasion onto plants is an effective method for geminivirus infection and virus-induced gene silencing. AB - Geminiviruses belong to a rapidly growing group of plant pathogens that contribute to crop losses in tropical and subtropical areas of the world. Geminivirus infection is a model for plant DNA replication and virus/host interactions. Geminiviruses are also used as vectors to induce silencing of endogenous genes in several plant species. A method was analyzed for inoculating geminiviruses using plasmid DNA rubbed onto leaves in the presence of an abrasive (DNA abrasion). Although the use of DNA abrasion to inoculate geminiviruses has been described previously, the technique has fallen out of favor and has not been systematically optimized. However, consistent efficiencies of 100% infection rates can be achieved by DNA abrasion. The symptoms of Tomato Golden Mosaic Virus or Cabbage Leaf Curl Virus infection on Nicotiana benthamiana were similar in timing and appearance to the symptoms observed in plants inoculated using Agrobacterium as the delivery method. More importantly, silencing of an endogenous gene was highly efficient when a geminivirus silencing vector was inoculated by the DNA abrasion method. Other plant species successfully inoculated with geminiviruses by DNA abrasion were Nicotiana tabacum, Capsicum annuum and Nicandra physalodes. Unfortunately, Arabidopsis thaliana could not be infected with Cabbage Leaf Curl Virus using leaf abrasion, demonstrating limitation of the method. However, leaf abrasion to inoculate geminiviruses is an easy and inexpensive method that should be considered as an accessible technique to the growing number of researchers using geminiviruses. PMID- 17337071 TI - The functional relationship between yawning and vigilance. AB - BACKGROUND: Although yawning is a ubiquitous and phylogenetically old phenomenon, its origin and purpose remain unclear. The study aimed at testing the widely held hypothesis that yawning is triggered by drowsiness and brings about a reversal or suspension of the process of falling asleep. METHODS: Subjects complaining of excessive sleepiness were spontaneously yawning while trying to stay awake in a quiet and darkened room. Changes in their electroencephalogram (EEG) and heart rate variability (HRV) associated with yawning were compared to changes associated with isolated voluntary body movements. Special care was taken to remove eye blink- and movement-artefacts from the recorded signals. RESULTS: Yawns were preceded and followed by a significantly greater delta activity in EEG than movements (p< or =0.008). After yawning, alpha rhythms were attenuated, decelerated, and shifted towards central brain regions (p< or =0.01), whereas after movements, they were attenuated and accelerated (p<0.02). A significant transient increase of HRV occurred after the onset of yawning and movements, which was followed by a significant slow decrease peaking 17s after onset (p<0.0001). No difference in HRV changes was found between yawns and movements. CONCLUSIONS: Yawning occurred during periods with increased drowsiness and sleep pressure, but was not followed by a measurable increase of the arousal level of the brain. It was neither triggered nor followed by a specific autonomic activation. Our results therefore confirm that yawns occur due to sleepiness, but do not provide evidence for an arousing effect of yawning. PMID- 17337070 TI - Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR. AB - HTLV-1 and HTLV-2 are highly related delta-retroviruses that infect and transform T-lymphocytes, but have distinct pathogenic properties. HTLV replication and survival requires the expression of multiple gene products from an unspliced and a series of highly related alternatively spliced mRNA species. To date, the comparative levels of all known HTLV-1 and HTLV-2 viral mRNAs in different transformed cell lines and at different stages of virus infection have not been assessed. In this study, we compiled a series of oligonucleotide primer pairs and probes to quantify both HTLV-1 and HTLV-2 mRNA species using real-time RT-PCR. The optimized reaction for detection of each mRNA had amplification efficiency greater than 90% with a linear range spanning 25-2.5 x 10(7) copies. The R(2)'s of all standard curves were greater than 0.97. Quantitation of HTLV mRNAs between different cell lines showed variability (gag/pol>or=tax/rex>env>or=accessory proteins), but the overall levels of each mRNA relative to each other within a cell line were similar. These results provide a method to quantify all specific mRNAs from both HTLV-1 and HTLV-2, which can be used to evaluate further viral gene expression and correlate transcript levels to key stages of the virus life cycle and ultimately, pathogenesis. PMID- 17337072 TI - The KH and S1 domains of Escherichia coli polynucleotide phosphorylase are necessary for autoregulation and growth at low temperature. AB - PNPase is a phosphate-dependent exonuclease of Escherichia coli required for growth in the cold. In this work we explored the effect of specific mutations in its two RNA binding domains KH and S1 on RNA binding, enzymatic activities, autoregulation and ability to grow at low temperature. We removed critical motifs that stabilize the hydrophobic core of each domain, as well as made a complete deletion of both (DeltaKHS1) that severely impaired PNPase binding to RNA. Nevertheless, a residual RNA binding activity, possibly imputable to catalytic binding, could be observed even in the DeltaKHS1 PNPase. These mutations also resulted in significant changes in the kinetic behavior of both phosphorolysis and polymerization activities of the enzyme, in particular for the double mutant Pnp-DeltaKHS1-H. Additionally, PNPases with mutations in these RNA binding domains did not autoregulate efficiently and were unable to complement the growth defect of a chromosomal Deltapnp mutation at 18 degrees C. Based on these results it appears that in E. coli the RNA binding domains of PNPase, in particular the KH domain, are vital at low temperature, when the stem-loop structures present in the target mRNAs are more stable and a machinery capable to degrade structured RNA may be essential. PMID- 17337073 TI - Acute coronary syndrome due to high aortocoronary junction of the right coronary artery: the value of multislice CT. AB - High aortocoronary junction of the right coronary artery (RCA) above the sinus of Valsalva is not rare. There is controversy whether it is a benign finding or a life threatening condition. A 47-year-old male, who had recurrent acute coronary syndrome underwent coronary arteriogram twice showing only an aberrant origin of the RCA ostium from the left coronary cuspid. Sixty-four cut multislice computed tomogram (MSCT) of the coronary arteries showed the RCA ostium taking off above the right sinus of Valsalva. The RCA then shifted leftward and coursed between the great vessels. Compression of its proximal segment as it passed between the aorta and pulmonary artery explained the recurrent coronary attack. High take-off of the RCA ostium above its cuspid should be considered a risk factor for acute coronary attack under certain conditions. MSCT is valuable in providing better spatial images compared to the more invasive conventional coronary arteriography. PMID- 17337074 TI - A malignant diagnosis. PMID- 17337075 TI - Cardiovocal syndrome after transradial cardiac catheterization: An unusual complication. PMID- 17337076 TI - Early diagnosis of cardiac sarcoidosis using magnetic resonance imaging. AB - Cardiac sarcoidosis can be a challenging diagnosis to make. The introduction of newer technologies, such as cardiac magnetic resonance imaging and positron emission tomography, have meant earlier diagnosis is possible. This is crucial as early treatment improves symptoms and prognosis. PMID- 17337077 TI - Acute coronary syndrome in an adult with anomalous origin of the left anterior descending coronary artery from the pulmonary trunk. AB - Anomalous origin of the left anterior descending coronary artery is a very rare coronary vascular anomaly, especially in adults. We describe the case of a 45 year-old woman who presented with an acute coronary syndrome. Coronary angiography revealed an anomalous origin of the left anterior descending coronary artery from the main pulmonary trunk, with collateral filling from both the left circumflex and the right coronary artery. Treatment of choice of this coronary anomaly is usually surgical repair, while intense antithrombotic therapy should be considered, especially if the anomalous vessel is ectatic. PMID- 17337078 TI - Atrial fibrillation and anabolic steroid abuse. AB - Atrial fibrillation (AF) is the most common sustained arrhythmia to occur in humans. Several predisposing substrates such as increasing age, heart failure, hypertension and valvular heart disease have been identified. The use of illicit drugs as the substrate for AF is not frequently recognized. PMID- 17337079 TI - Biochemical anti-opioid action of NPFF2 receptors in rat spinal cord. AB - Neuropeptide FF (NPFF) agonists counteract the cellular opioid actions. We demonstrate for the first time a biochemical anti-opioid effect of NPFF receptors in the rat spinal cord by using the [(35)S]GTPgammaS binding assay in autoradiography. The mu agonist DAMGO as well as the potent and selective NPFF(2) agonist dNPA, stimulated [(35)S]GTPgammaS binding at different optimal GDP concentrations. dNPA decreased the effects induced by DAMGO alone; the maximal of G-protein coupling was decreased but not the potency of opioid agonist. We conclude that NPFF(2) receptors are coupled to G-protein in the rat spinal cord and could exert a molecular anti-opioid effect. PMID- 17337080 TI - The heparanome--the enigma of encoding and decoding heparan sulfate sulfation. AB - Heparan sulfate (HS) is a cell surface carbohydrate polymer modified with sulfate moieties whose highly ordered composition is central to directing specific cell signaling events. The ability of the cell to generate these information rich glycans with such specificity has opened up a new field of "heparanomics" which seeks to understand the systems involved in generating these cell type and developmental stage specific HS sulfation patterns. Unlike other instances where biological information is encrypted as linear sequences in molecules such as DNA, HS sulfation patterns are generated through a non-template driven process. Thus, deciphering the sulfation code and the dynamic nature of its generation has posed a new challenge to system biologists. The recent discovery of two sulfatases, Sulf1 and Sulf2, with the unique ability to edit sulfation patterns at the cell surface, has opened up a new dimension as to how we understand the regulation of HS sulfation patterning and pattern-dependent cell signaling events. This review will focus on the functional relationship between HS sulfation patterning and biological processes. Special attention will be given to Sulf1 and Sulf2 and how these key editing enzymes might act in concert with the HS biosynthetic enzymes to generate and regulate specific HS sulfation patterns in vivo. We will further explore the use of knock out mice as biological models for understanding the dynamic systems involved in generating HS sulfation patterns and their biological relevance. A brief overview of new technologies and innovations summarizes advances in the systems biology field for understanding non-template molecular networks and their influence on the "heparanome". PMID- 17337081 TI - [Evaluation of analgesic protocol with nitrous oxide and EMLA cream during botulinum toxin injections in children]. AB - AIMS: To evaluate the efficiency and tolerance of analgesic treatment with nitrous oxide and topical eutectic mixture of local anesthetics (EMLA) in children undergoing botulinum toxin injections for focal spasticity. METHODS: Prospective study including 40 consecutive patients aged 2 to 17 years, most with cerebral palsy, undergoing botulinum toxin injections. Ten had severe cerebral palsy with cognitive deficiency. For most patients the treatment involved several muscles, with several injections per muscle. The total number of injections varied from 1 to 25. The procedure was performed with topical anesthesia with EMLA and inhalation of nitrous oxide (50% nitrous oxide, 50% oxygen). Reactions were recorded by the staff (a practician, a nurse, an auxiliary staff member and an internist) and whether they related to the injection or were nonspecific. RESULTS: A total of 45% of patients showed no clinical manifestation of pain; for 30%, reactions were crying and withdrawal directly related to the injections; and for 25%, manifestations seemed nonspecific and mainly related to overall anxiety and discomfort. In 3 patients, moderate side effects were observed (visual hallucinations and euphoria). DISCUSSION: Nitrous oxide analgesic with topical EMLA was efficient for children undergoing botulinum toxin injections but remained insufficient for half of our patients, and modification of the protocol is needed in some cases. Precise evaluation of acute pain is difficult in children with major cognitive deficits. Clinical manifestations are related to pain but also to overall anxiety and stress. PMID- 17337082 TI - [Asymptomatic blunt vertebral artery injury after cervical spine nonpenetrating trauma]. AB - OBJECTIVE: To show the possibility of vertebral injury after cervical spine trauma. METHOD: We observed 2 cases of asymptomatic thrombosis of the vertebral artery after cervical fracture. DISCUSSION: Thrombosis of the vertebral artery is acute in 20% of cases of cervical trauma. It may be asymptomatic. Magnetic resonance angiography is the best noninvasive investigation for such cases to systematically detect the complication. Treatment with anticoagulants or antiaggregants should be initiated. PMID- 17337083 TI - Medical specialists' allocation of working time. AB - The aim of this study is to map the time-allocation of medical specialists and to examine how it relates to internal organising of work, wage incentives, physicians' preferences and the demand structure in the population. With regards to internal organising of work and wage incentives, special attention is granted to the private-public divide in specialised healthcare. Survey data from 1183 Norwegian physicians is employed and the empirical models are estimated by means of ordinary least squares (OLS) regression analysis, linear logit analysis, binomial logistic regression analysis and multilevel analysis. Physicians working in the private sector and physicians combining private and public work spend relatively more time on patient-assignments than their public counterparts, while public physicians allocate more time to administrative and research/educational tasks. These findings support the proposition that work time allocations mirror the differences in on-call commitments, wage incentives and the division of labour between the sectors. Furthermore, whereas the demand-specific set of variables in the model contributes moderately to the explanation of working time allocation, internal organising of work and physicians' preferences exert significant effects across the sectors. Future research should focus on physicians' time allocation since the topic will remain relevant as the European Union's (EU's) Working Time Directive continues to shake the European healthcare systems with traditions for long workdays. PMID- 17337084 TI - The survival outcomes of patients with resected non-small cell lung cancer differ according to EGFR mutations and the P21 expression. AB - The aims of this study were to evaluate the prognostic implications of patients with epidermal growth factor receptor (EGFR) mutations and a p21 expression, and to determine their associations in resected non-small cell lung cancer (NSCLC) patients. We sequenced exons 18-21 of the EGFR tyrosine kinase domain by performing mutation analysis of tissues from patients that suffered with NSCLC and who also had undergone surgical resection. The expressions of p21 and p53 were analyzed using immunohistochemistry. We detected EGFR mutations in 24 of 97 patients (25%). EGFR mutations were more frequent in the people who had never smoked than in the smokers (33% versus 14%, respectively; P=.028). The presence of EGFR mutations had no effect on survival. The expression of p21 in the patients with wild-type EGFR tended to be associated with better survival. However, the expression of p21 in the patients with EGFR mutations was associated with poor overall survival (P=.006). The five-year survival rates were 17% for the patients with EGFR mutations and p21 positivity (Group I), 44% for the patients with wild type EGFR (Group II), and 75% for the patients with EGFR mutation and no p21 positivity (Group III) (P=.036). Multivariate analysis that was corrected for age, gender and cancer stage revealed different overall survival outcomes according to the three groups (P=.004). There was no significant correlation between the expressions of p21 and p53. Survival outcomes in the patients with resected NSCLC may be correlated with the presence of a p21 expression and EGFR mutations. PMID- 17337085 TI - Polymorphism of selected enzymes involved in detoxification and biotransformation in relation to lung cancer. AB - Available data indicate that there are significant differences in individual susceptibility to lung cancer within the human population. It is believed to be underlie by inherited genetic predispositions related to the genetic polymorphism of several enzymes involved in the detoxification and xenobiotic metabolism. In this review, we collect and discuss the evidence reported up to date on the association between lung cancer and genetic polymorphism of cytochromes P450, N acetyltransferase, glutathione S-transferases, microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, myeloperoxidase and glutathione peroxidase. All these genes might appear to be candidates for lung cancer susceptibility genes, nevertheless, the present state of the art still offers only a limited explanation of the link between such polymorphisms and increased risk of lung cancer. PMID- 17337086 TI - A novel triplet regimen with paclitaxel, carboplatin and gemcitabine (PACCAGE) as induction chemotherapy for locally advanced unresectable non small cell lung cancer (NSCLC). AB - Phase II study of 3 cycles of triplet induction chemotherapy (response, toxicity) followed by radiotherapy in locally advanced non small cell lung cancer (NSCLC). BACKGROUND: Patients with locally advanced inoperable non-small cell lung cancer are currently treated with concomitant or sequential chemotherapy and radiotherapy. However, the outcome of existing treatment modalities is unsatisfactory. Development of new strategies including more efficient systemic chemotherapy is warranted. OBJECTIVE: To study the antitumour activity and toxicity of a triplet combination of paclitaxel, carboplatin and gemcitabine as induction chemotherapy before radiotherapy, in locally advanced NSCLC and to evaluate time to progression and survival. METHODS: Three cycles of paclitaxel (175 mg/m(2) by 3h infusion on day 1), carboplatin (AUC 5mg/(mlmin) by IV bolus on day 1) and gemcitabine (1000 mg/m(2) by IV bolus on day 1 and 8) were administered every 3 weeks in reasonably fit patients. Fractionated radiotherapy with curative intent was initiated 4 weeks after the last chemotherapy administration. Toxicity was assessed weekly during cycle 1 and on day 1 and 8 in cycles 2 and 3. Response evaluation was performed at the end of cycle 3. RESULTS: Forty-eight patients (20 stage IIIA and 28 stage IIIB) received a total of 134 cycles of chemotherapy. Forty-two patients received the intended 3 cycles. Thirty patients obtained an objective response (1 complete and 29 partial response) or 62.5% on the intent to treat analysis (95% confidence interval: 49-76%). None of the responders became eligible for surgery. The median time to progression and survival for all patients was 10.1 and 15.7 month, respectively. A significant difference was observed in survival parameters between stage IIIA and stage IIIB patients. Haematological toxicity grade 3/4, mainly neutropenia and thrombocytopenia, was most prominent on day 15 of the treatment cycles. Haematological support by means of recombinant erythropoietin, red blood cell or platelet transfusion, filgrastim administration or a combination was needed in 21 patients. None of the patients discontinued chemotherapy because of haematotoxicity. Grade 3/4 non-haematological toxicity leading to chemotherapy withdrawal occurred early during induction (2 and 1 in cycles 1 and 2, respectively). CONCLUSION: Three cycles of the novel triplet combination of paclitaxel, carboplatin and gemcitabine (PACCAGE) is an active and feasible induction regimen for patients with locally advanced inoperable NSCLC. Neutropenia and to a lesser extent thrombocytopenia represent the main haematological toxicity. Whether this triplet regimen can improve outcome when compared to specific cisplatin doublet regimens should be evaluated in a phase III study. PMID- 17337087 TI - Epistasis between deleterious mutations and the evolution of recombination. AB - Epistasis and the evolution of recombination are closely intertwined: epistasis generates linkage disequilibria (i.e. statistical associations between alleles), whereas recombination breaks them up. The mutational deterministic hypothesis (MDH) states that high recombination rates are maintained because the breaking up of linkage disequilibria generated by negative epistasis enables more efficient purging of deleterious mutations. However, recent theoretical and experimental work challenges the MDH. Experimental evidence suggests that negative epistasis, required by the MDH, is relatively uncommon. On the theoretical side, population genetic models suggest that, compared with the combined effects of drift and selection, epistasis generates a negligible amount of linkage disequilibria. Here, we assess these criticisms and discuss to what extent they invalidate the MDH as an explanation for the evolution of recombination. PMID- 17337088 TI - Effects of the pig renal epithelial cell line LLC-PK1 and its conditioned medium on the phenotype of porcine microglia in vitro. AB - Microglia are dispersed throughout the central nervous system. Under physiological circumstances they display a 'ramified' resting phenotype. In different neuropathologies microglia reversibly transform into the activated form, an amoeboid phagocyte with a broad spectrum of immune effector functions. In this study, a coculture of porcine microglia and the pig renal epithelial cell line LLC-PK1 was used to investigate microglial cell biology. The morphology of the cocultures was elucidated as well as the functionality of the microglia cells by proliferation, superoxide and phagocytosis assays. Our results demonstrate that direct intercellular contact between the two cell types was necessary for microglia to acquire a ramified morphology. Moreover, the conditioned medium of the renal cells promoted proliferation of microglia, inhibited giant cell formation and stimulated microglia to retain their capability to generate superoxide and to perform phagocytosis. In conclusion, we have constructed a cell culture system showing differentiation of microglia in vitro and keeping them in optimal conditions. PMID- 17337089 TI - Current considerations about Merkel cells. AB - Since the discovery of Merkel cells by Friedrich S. Merkel in 1875, knowledge of their structure has increased with the progression of new technologies such as electron and laser microscopy, and immunohistochemical techniques. For most vertebrates, Merkel cells are located in the basal layer of the epidermis and characterized by dense-core granules that contain a variety of neuropeptides, plasma membrane spines and cytoskeletal filaments consisting of cytokeratins and desmosomes. The presence of the two latter structures would suggest that Merkel cells originate from the epidermis rather than from the neural crest, even though such a hypothesis is not unanimously accepted. The function of the Merkel cell is also very controversial. For a long time, it has been accepted that Merkel cells with associated nerve terminals act as mechanoreceptors although the transduction mechanism has not yet been elucidated. Merkel cells that do not make contact with nerve terminals have an endocrine function. The present review aims to shed new and comparative light on this field with an attempt to investigate the stimuli that Merkel cells are able to perceive. PMID- 17337090 TI - Treatment of acute Old World cutaneous leishmaniasis: a systematic review of the randomized controlled trials. AB - BACKGROUND: Cutaneous leishmaniasis (CL) is caused by different species of Leishmania and transmitted by the bite of infected sand flies. It is a health problem in many countries. OBJECTIVE: This study was performed to assess the evidence for the efficacy of different therapeutic modalities for acute Old World CL, which is usually caused by L major and L tropica. METHODS: Evidence was reviewed according to the hierarchy of evidence. Because there have been no published systematic reviews on this topic to date, the primary source of evidence was individual randomized controlled trials (RCTs). Multiple databases were systematically searched. Using independent double review and published quality review criteria, articles were rated as good, fair, or poor. Treatment benefit data were tabulated, and conclusions were based on the rated strength of published evidence. RESULTS: In all, 50 RCTs met inclusion criteria consisting of 5515 patients in 119 study arms. Reviewed trials were highly variable in quality and methods and generally provide weak evidence for treatment of acute Old World CL. LIMITATIONS: The quality of included studies was generally poor. CONCLUSIONS: Well-designed randomized, double-blind, controlled trials should be designed and conducted to find better evidence for the treatment of acute Old World CL. PMID- 17337091 TI - Association between the anatomic distribution of melanoma and sex. AB - BACKGROUND: Anatomic distribution of melanoma, thought to be different between men and women, has not been studied in the United States since the 1970s, although lifestyle and clothing habits have changed since then. OBJECTIVE: To determine whether the anatomic distribution of melanoma varied between men and women at our institution in 2004 and in the 1970s, and to assess whether the anatomic distribution has changed over time. METHODS: We recorded the body location of initial primary cutaneous melanomas and assessed other variables of interest for 152 patients seen in our clinic in 2004 and in 397 patients seen between 1972 and 1977. Logistic regression was used for analysis. RESULTS: For the 2004 patients, males had an increased relative risk compared to females of developing a melanoma on their head and neck (relative risk ratio [RRR] = 3.33; P = .01). For the 1970s patients, this difference was not found, but males in the 1970s had higher odds of developing melanoma on their upper back, chest, and abdomen, while females in the 1970s had higher odds of developing melanoma on the upper extremity and lower extremity, particularly the lower legs and feet. Examining differences over time, we found that women in 2004 had a decreased relative risk of developing a melanoma on the lower extremities as opposed to the trunk as compared to the 1970s (RRR = 0.42; P < .01). We also found that women had increased odds of developing a melanoma on the chest in 2004 compared to the 1970s (OR = 2.65; P = .04), while men had increased odds of developing a melanoma on their lower legs in 2004 compared to the 1970s (OR = 3.18; P = .02). LIMITATIONS: The study was performed at a single academic center and the results may not generalize to all melanoma populations. There may be important unexamined confounders. CONCLUSIONS: There were significant differences between men and women in the anatomic distribution of melanoma in 2004 patients and in 1970s patients, but the nature of those differences changed over time. PMID- 17337093 TI - Manual in-line stabilization for acute airway management of suspected cervical spine injury: historical review and current questions. AB - Direct laryngoscopy with manual in-line stabilization is standard of care for acute trauma patients with suspected cervical spine injury. Ethical and methodologic constraints preclude controlled trials of manual in-line stabilization, and recent work questions its effectiveness. We searched MEDLINE, Index Medicus, Web of Knowledge, the Cochrane Database, and article reference lists. According to this search, we present an ancestral review tracing the origins of manual in-line stabilization and an analysis of subsequent studies evaluating the risks and benefits of the procedure. All manual in-line stabilization data came from trials of uninjured patients, cadaveric models, and case series. The procedure was adopted because of reasonable inference from the benefits of stabilization during general care of spine-injured patients, weak empirical data, and expert opinion. More recent data indicate that direct laryngoscopy and intubation are unlikely to cause clinically significant movement and that manual in-line stabilization may not immobilize injured segments. In addition, manual in-line stabilization degrades laryngoscopic view, which may cause hypoxia and worsen outcomes in traumatic brain injury. Patients intubated in the emergency department with suspected cervical spine injury often have traumatic brain injury, but the incidence of unstable cervical lesions in this group is low. The limited available evidence suggests that allowing some flexion or extension of the head is unlikely to cause secondary injury and may facilitate prompt intubation in difficult cases. Despite the presumed safety and efficacy of direct laryngoscopy with manual in-line stabilization, alternative techniques that do not require direct visualization warrant investigation. Promising techniques include intubation through supraglottic airways, along with video laryngoscopes, optical stylets, and other imaging devices. PMID- 17337092 TI - Pneumococcal bacteremia in febrile infants presenting to the emergency department before and after the introduction of the heptavalent pneumococcal vaccine. AB - STUDY OBJECTIVE: Fever is among the most common presenting complaints of infants and children younger than 3 years who present to the emergency department (ED). The evaluation and management of the febrile child is evolving rapidly. We compare the proportion of pneumococcal bacteremia between febrile infants and children younger than 3 years who had and had not received the heptavalent pneumococcal vaccine and who had received blood culture tests in our ED. METHODS: We performed a non-concurrent prospective observational cohort study, with a standardized medical record review to collect data of patients treated in the ED of a tertiary care military hospital during 24 months. Patients were eligible if they were younger than 36 months and had a temperature greater than or equal to 100.4 degrees F (38 degrees C). A data collection sheet was used to abstract age, temperature, and whether CBC count and blood cultures were obtained. Heptavalent pneumococcal vaccine status and blood culture results were obtained through review of the computerized medical record. Descriptive analysis was used for comparing the 2 groups. Group size analysis was based on the prevalence of occult bacteremia caused by Pneumococcus before the introduction of heptavalent pneumococcal vaccine. Interobserver variation was assessed by independent review of 10% of abstracted records. The main outcome measure was the proportion of positive pneumococcal blood cultures in infants and children younger than 3 years who had received at least 1 vaccination of heptavalent pneumococcal vaccine versus those who had not. RESULTS: Three thousand five hundred seventy-one patients met entry criteria; 1,428 had blood cultures obtained, and 833 of them received at least 1 immunization of heptavalent pneumococcal vaccine. All groups were similar in age, sex, and temperature. Positive blood culture results, including probable contaminants, were obtained for 4.2% (58/1,383) of the patients. In the heptavalent pneumococcal vaccine group, there were 0 of 833 (0%) positive pneumococcal blood cultures compared with 13 of 550 (2.4%) in the unimmunized group (P<.001; 95% confidence interval 1.4% to 3.3%). CONCLUSION: Pneumococcal bacteremia was found to be lower in our patients who had received the heptavalent pneumococcal vaccine than in the patients who had not. PMID- 17337094 TI - Intracerebroventricular administration of galanin or galanin receptor subtype 1 agonist M617 induces c-Fos activation in central amygdala and dorsomedial hypothalamus. AB - The neuropeptide galanin and galanin receptors are widespread throughout cortical, limbic and midbrain areas implicated in reward, learning/memory, pain, drinking and feeding. While many studies have shown that galanin produces a variety of presynaptic and post-synaptic responses, work studying the effects of galanin on neural activation is limited. The present study examined patterns of c Fos immunoreactivity resulting from intracerebroventricular administration of galanin versus saline injection in awake rats. An initial comprehensive qualitative survey was conducted to identify regions of high c-Fos expression followed up with quantitative analysis. Galanin induced a significant increase in c-Fos levels relative to saline-treated controls in dorsomedial hypothalamus and in the central nucleus of the amygdala. This pattern of activation was also produced by galanin receptor type 1 agonist M617. The present findings confirm that galanin upregulates c-Fos activation in hypothalamic nuclei, and supports roles for galanin in central amygdala-mediated regulation of stress-responses, food intake, and Pavlovian conditioning. PMID- 17337095 TI - Synthesis of novel 3-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)-guanidine derivatives as potential antitumor agents. AB - Novel 3-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)guanidine derivatives have been synthesized as potential anticancer agents. The in vitro antitumor activity of these compounds has been evaluated in the US National Cancer Institute (NCI), and relationships between structure and antitumor activity are discussed. The prominent compound was 1-allyl-2-[4-chloro-5-(4-chlorophenylcarbamoyl)-2 methylthiobenzenesulfonyl]-3-(5-nitrofurfurylideneamino)guanidine (8) with remarkable activity against 21 human tumor cell lines representing leukemia, lung, colon, melanoma, ovarian, renal, prostate and breast (GI(50)=0.3 3.0microM), and selectivity toward leukemia RPMI-8226 cell line (GI(50)=0.3microM, TGI=1.4microM). PMID- 17337096 TI - Synthesis of novel triheterocyclic thiazoles as anti-inflammatory and analgesic agents. AB - Triheterocyclic thiazoles containing coumarin and carbostyril (1-aza coumarin) have been synthesized by the reaction of the in situ generated 4-thioureidomethyl carbostyril and 3-bromoacetyl coumarins. The new compounds have been tested for their in vivo analgesic and anti-inflammatory activities. Qualitative SAR studies indicate that, the chloro substitution at C-7 in carbostyril and 6,8-dibromo substitution in the coumarin ring enhance anti-inflammatory activity. These compounds were also found to provide significant protection against acetic acid writhing in animal models. All the compounds have been characterized by IR, (1)H NMR, (13)C NMR and mass spectrometry. PMID- 17337097 TI - Synthesis and in vitro antimicrobial activity of new 2-[p-substituted-benzyl]-5 [substituted-carbonylamino]benzoxazoles. AB - Some new 2-(benzyl/p-chlorobenzyl)-5-[(substituted thienyl/phenyl/phenylthiomethyl/benzyl)carbonylamino]benzoxazole derivatives have been synthesized by reacting 5-amino-2-(benzyl/p-chlorobenzyl)benzoxazoles with appropriate carboxylic acid chlorides. The structures of the synthesized compounds were confirmed by IR, (1)H NMR and MASS spectral data. In vitro antimicrobial activities of the compounds were investigated using twofold serial dilution technique against different two Gram-positive, two Gram-negative bacteria and three Candida spp. in comparison with standard drugs. Microbiological results indicated that the newly synthesized 2-(benzyl/p chlorobenzyl)-5-[(substituted thienyl/phenyl/phenylthiomethyl/benzyl)carbonylamino]benzoxazole derivatives (3 12) possessed a broad spectrum of activity having MIC values of 6.25-100 microg/ml against the tested microorganisms. Especially, with an MIC value of 6.25 microg/ml, 2-(p-chlorophenyl)-5-[(2,5 dimethylphenyl)carbonylamino]benzoxazole 4 displayed the same activity against Candida albicans as the standard drug clotrimazole. PMID- 17337098 TI - [Lyme disease could mimic dermatomyositis]. AB - We report a dermatomyositis associated with Lyme disease. OBSERVATION: A 73-years old woman has developed for 5 months an asthenia, a periorbital oedema and a forearm's skin infiltration without other signs suggesting of dermatomyositis. Laboratory studies showed an elevation of muscular enzymes, and inflammation signs. The skin and the muscles biopsies were compatible with the diagnostic of dermatomyositis. The patient was seropositive for Lyme disease. The patient was efficiently treated with doxycycline. DISCUSSION: Lyme disease could mimic a dermatomyositis. Indeed, Lyme disease should be considered as a differential diagnosis of dermatomyositis. PMID- 17337099 TI - [New insights and perspectives in the management of dyslipidemia]. AB - PURPOSE: Recent end point trials of lipid-lowering drugs have shown that patients at very high-risk for coronary disease benefit from treatments that lowers low density lipoprotein cholesterol (LDL cholesterol) plasma levels< or =70 mg/dl and that patients with at least 2 risk factors benefit from LDL cholesterol levels< or =100 mg/dl. Epidemiologic studies have shown that the concentration of high density lipoprotein cholesterol (HDL cholesterol) is a strong, independent, inverse predictor of coronary disease risk. Innovative pharmacological approaches to raise low HDL cholesterol levels are currently of considerable interest, especially for patients with type 2 diabetes or metabolic syndrome. RESULTS: Rosuvastatin has shown superior efficacy in lowering LDL cholesterol, although evidence of clinical benefit is actually lacking. Ezetimibe is a lipid-lowering drug that inhibits absorption of dietary and biliary cholesterol. Its co administration with statin has given very interesting results. Niacin is the most effective of currently available options for raising HDL cholesterol, although tolerability can be an issue, with serious side effects such as loss of glucose control and liver toxicity. Flushing may occur in 80% of treated patients. Two CETP inhibitors have shown therapeutical efficacy to raise HDL cholesterol, but clinical benefit remains uncertain. PMID- 17337100 TI - [Actinomyces odontolyticus isolation during prosthetic aortic graft infection with paraprosthetic duodenal fistula]. AB - INTRODUCTION: Prosthetic vascular graft infection is a rare complication of vascular surgery. We report a case with graft enteric fistula and Actinomyces odontolyticus bacteremia. EXEGESIS: A 73 year-old man with a prosthetic aortic graft and who had a parodontal disease, has been hospitalised for fever of unknown origin. Blood cultures grew with Escherichia coli and Actinomyces odontolyticus. The imaging studies indicated graft infection. Laparotomy has confirmed the diagnosis and highlighted a polymicrobial infection and a paraprosthetic duodenal fistula. A review of the literature's data concerning prosthetic vascular graft infections is made. The role of Actinomyces odontolyticus in that case is discussed. CONCLUSION: Prosthetic aortic graft infection due to graft enteric fistula is usually a polymicrobial infection and is a late complication of aortic surgery. Imaging is essential for the diagnosis of prosthetic aortic graft infection. It is possible that Actinomyces odontolyticus has contributed to prosthesis infection in this case. PMID- 17337101 TI - Lycopene differentially induces quiescence and apoptosis in androgen-responsive and -independent prostate cancer cell lines. AB - BACKGROUND & AIMS: Lycopene has been credited with a number of health benefits including a decrease in prostate cancer risk. Our study investigates the molecular mechanism underlying anti-cancer activity of lycopene-based products in androgen-responsive (LNCaP) and androgen-independent (PC3) cells. METHODS: The effect of lycopene-based agents on prostate cancer growth and survival were examined using proliferation assays, bromodeoxyuridine incorporation and flow cytometric analysis of cellular DNA content. Biochemical effects of lycopene treatment were investigated by immunoblotting for changes in the absolute levels and phosphorylation states of cell cycle regulatory and signalling proteins. RESULTS: LNCaP and PC3 cells treated with the lycopene-based agents undergo mitotic arrest, accumulating in G0/G1 phase. Immunoblot screening indicated that lycopene's antiproliferative effects are likely achieved through a block in G1/S transition mediated by decreased levels of cyclins D1 and E and cyclin dependent kinase 4 and suppressed Retinoblastoma phosphorylation. These responses correlated with decreased insulin-like growth factor-I receptor expression and activation, increased insulin-like growth factor binding protein 2 expression and decreased AKT activation. Exposure to lycopene at doses as low as 10 nM for 48 h induced a profound apoptotic response in LNCaP cells. In contrast PC3 cells were resistant to apoptosis at doses up to 1 microM. CONCLUSIONS: Lycopene exposure can suppress phosphatidylinositol 3-kinase-dependent proliferative and survival signalling in androgen-responsive LNCaP and androgen-independent PC3 cells suggesting that the molecular mechanisms for the cytostatic and cytotoxic actions of lycopene involve induction of G0/G1 cell cycle arrest. This study supports further examination of lycopene as a potential agent for both the prevention and treatment of prostate cancer. PMID- 17337102 TI - Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin. AB - Influenza virus is a highly infectious respiratory pathogen that results in severe morbidity and mortality. The current licensed trivalent vaccine formulations in the U.S. are made from virus grown in allantoic fluid from infected hen eggs that is then chemically inactivated and split into subunit components. These vaccines elicit antibodies, primarily to the viral hemagglutinin (HA), which are efficacious in healthy adults, but are limited in protecting high risk individuals, such as the elderly and immunocompromised. To address the need for improved influenza vaccines and the limitations of egg-based manufacturing, we have engineered an influenza virus-like particle (VLP) as a new generation of non-egg or non-mammalian cell culture-based candidate vaccine against influenza infection. VLPs, based on the A/Fujian/411/2002 (H3N2) isolate, were purified from the supernatants of Spodoptera frugiperda Sf9 insect cells following infection of baculovirus vectors encoding an expression cassette comprised of only three influenza virus structural proteins, hemagglutinin (HA), neuraminidase (NA), and matrix (M1). Mice or ferrets were vaccinated intramuscularly with VLPs in a dose sparing experiment, based on HA concentration (3 microg-24 ng), and the immune responses were compared to responses elicited in animals vaccinated with recombinant HA (rHA) or inactivated whole influenza virions (WIV). All vaccinated animals had high titer anti-HA antibodies regardless of the vaccine immunogen and animals vaccinated with the highest doses of VLPs (3 microg and 600 ng) also had antibodies against NA. Purified rHA elicited primarily IgG1 antibodies, which is indicative of a T helper (Th) type 2 response, whereas mice vaccinated with the VLPs or WIV were associated with a dominant Th1 immune response (IgG2a and IgG2b). Interestingly, VLPs elicited antibodies that recognized a broader panel of antigenically distinct H3N2 viral isolates compared to rHA or WIV in a hemagglutination-inhibition (HAI) assay. PMID- 17337103 TI - Estimation of annual effective dose due to natural radioactive elements in ingestion of foodstuffs in tin mining area of Jos-Plateau, Nigeria. AB - Soils and food crops from a former tin mining location in a high background radiation area on the Jos-Plateau, Nigeria were collected and analyzed by gamma spectrometry to measure their contents of 40K, 238U and 232Th. As well as collecting samples, in situ dose rates on farms were measured using a precalibrated survey meter. Activity concentrations determined in food crops were compared with the local food derivatives or diets to investigate the possible removal or addition of radionuclides during food preparation by cooking or other means. Potassium-40 was found to contribute the highest activity in all the food products. The activity concentration of 40K, 238U and 232Th in local prepared diets ranged between 60 and 494 Bq kg-1, between BDL and 48 Bq kg-1 and between BDL and 17 Bq kg-1, respectively. The internal effective dose to individuals from the consumption of the food types was estimated on the basis of the measured radionuclide contents in the food crops. It ranged between 0.2 microSv y-1 (beans) and 2164 microSv y-1 (yam) while the annual external gamma effective dose in the farms due to soil radioactivity ranged between 228 microSv and 4065 microSv. PMID- 17337104 TI - Fluxes of oxidised and reduced nitrogen above a mixed coniferous forest exposed to various nitrogen emission sources. AB - Concentrations of nitrogen gases (NH(3), NO(2), NO, HONO and HNO(3)) and particles (pNH(4) and pNO(3)) were measured over a mixed coniferous forest impacted by high nitrogen loads. Nitrogen dioxide (NO(2)) represented the main nitrogen form, followed by nitric oxide (NO) and ammonia (NH(3)). A combination of gradient method (NH(3) and NO(x)) and resistance modelling techniques (HNO(3), HONO, pNH(4) and pNO(3)) was used to calculate dry deposition of nitrogen compounds. Net flux of NH(3) amounted to -64 ng N m(-2) s(-1) over the measuring period. Net fluxes of NO(x) were upward (8.5 ng N m(-2) s(-1)) with highest emission in the morning. Fluxes of other gases or aerosols substantially contributed to dry deposition. Total nitrogen deposition was estimated at -48 kg N ha(-1) yr(-1) and consisted for almost 80% of NH(x). Comparison of throughfall nitrogen with total deposition suggested substantial uptake of reduced N (+/-15 kg N ha(-1) yr(-1)) within the canopy. PMID- 17337106 TI - Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats. AB - Cadmium (Cd) is a neurotoxic metal, which induces oxidative stress and membrane disturbances in nerve system. The garlic compound diallyl tetrasulfide (DTS) has the cytoprotective and antioxidant activity against Cd induced toxicity. The present study was carried out to investigate the efficacy of DTS in protecting the Cd induced changes in the activity of acetylcholinesterase (AChE), membrane bound enzymes, lipid peroxidation (LPO) and antioxidant status in the brain of rats. In rats exposed to Cd (3mg/kg/day subcutaneously) for 3 weeks, a significant (P<0.05) increase in the levels of LPO and protein carbonyls along with significant (P<0.05) decrease in the levels of reduced glutathione (GSH) and total sulphydryl groups (TSH) and the activities of AChE, superoxide dismutase, catalase, glutathione peroxidase, gluthione-S-transeferase, membrane bound enzymes (ATPases: Na(+)K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase) were observed in brain tissue. Oral administration of DTS (40mg/kg/day) with Cd significantly (P<0.05) diminished the levels of LPO and protein carbonyls and significantly (P<0.05) increased the activities of ATPases, antioxidant enzymes, GSH and TSH in brain. These results indicate that DTS attenuate the LPO and alteration of antioxidant and membrane bound enzymes in Cd exposed rats, which suggest that DTS protects the brain function from toxic effects of Cd. PMID- 17337107 TI - Surveillance and risk factors on hysterectomy wound infection rate in Gran Canaria, Spain. AB - OBJECTIVES: Surveillance programs for nosocomial infection control may find out opportunities for improvement. The aim of this study was to determine the incidence of surgical site infection and their potential risk factors after hysterectomy in a tertiary hospital in Gran Canaria, Spain. STUDY DESIGN: Prospective study on patients undergoing abdominal or vaginal hysterectomy between 1st June 2000 and 31st December 2004. Surgical site infection incidence rates were calculated according to procedure, and National Nosocomial Infection Surveillance (NNIS) system risk categories. We also reviewed antimicrobial prophylaxis use and morbidity. To determine associate risk factors a multivariate analysis was performed. RESULTS: A total of 1540 women were surveyed; neoplasm (30.5%), obesity (24.3%), and diabetes (16.2%) grouped the main morbidity. About 81 cases (5.2%) met criteria for postoperative surgical site infection (6.0% for abdominal procedure and 3.1% for vaginal procedure). Most patients (86.4%) had adequate antimicrobial prophylaxis, but inadequacy was more frequent by vaginal (17.6%) than abdominal procedure (12.0%) (p=0.005). NNIS high-risk patients had significantly higher infection rates than did low-risk patients (p=0.01). The most common causative organism isolated was Escherichia coli (17.5%). Multivariate analysis showed obesity, inadequate antimicrobial prophylaxis, and abdominal procedure as the main risk factors. CONCLUSION: Rate of surgical site infection is high. Enhanced and multidisciplinary efforts are needed. PMID- 17337108 TI - Flow volume in the jugular vein and related hemodynamics in the branches of the jugular vein. AB - Venous reflux in the internal jugular vein branches (JB) was found frequently in patients of certain neurologic disorders. We hypothesized that the retrograde flow in JB is associated with retrograde hypertension transmitted from the internal jugular vein (IJV), which presumably underlies those neurologic disorders. In this study, we used color-Doppler imaging to evaluate the dynamic venous flow patterns in the IJV and its branches in 50 normal individuals (21 men, 29 women; mean age: 40.9 +/- 14.9 y, range: 22 to 70 y). The flow-direction of all detected JB (n = 100) was flowing into the IJV at baseline. During the Valsalva maneuver (VM), 38 JB (38%) had a retrograde-flow. Retrograde-flow in JB was significantly associated with IJV valve incompetence (OR = 7.6; 95% CI = 2.6 to 21.8; p = 0.0002) and greater IJV blood flow volume (blood flow volume >670 mL/min) (OR = 6.6; 95% CI = 1.8 to 24.5; p = 0.0052), both of which may reflect higher IJV pressure transmission during VM. The sonographic findings can be used in the future studies of diseases that are suspected to be related with retrograde cerebral venous hypertension due to an elevated IJV venous pressure. PMID- 17337109 TI - Use of ultrasound pulses combined with Definity for targeted blood-brain barrier disruption: a feasibility study. AB - We have developed a method to use low-intensity focused ultrasound pulses combined with an ultrasound contrast agent to produce temporary blood-brain barrier disruption (BBBD). This method could provide a means for the targeted delivery of drugs or imaging agents into the brain. In all our previous work, we used Optison as the ultrasound contrast agent. The purpose of this study was to test the feasibility of using the contrast agent Definity for BBBD. A total of 36 non-overlapping locations were sonicated through a craniotomy in experiments in the brains of nine rabbits (four locations per rabbit; ultrasound [US] frequency: 0.69 MHz; burst: 10 ms; pulse repetition frequency (PRF): 1 Hz; duration: 20 s). The peak negative pressure amplitude ranged from 0.2 to 1.5 MPa. An additional 11 locations were sonicated using Optison at pressure amplitude of 0.5 MPa. Definity and Optison dosages were the same as those used clinically for ultrasound imaging: 10 and 50 microl/kg, respectively. The probability for BBBD (determined using MRI contrast agent enhancement) as a function of pressure amplitude was similar to that found earlier with Optison. For both agents, the probability was estimated to be 50% at 0.4 MPa using probit regression. Histologic examination revealed small, isolated areas of extravasated erythrocytes in some locations. At 0.8 MPa and higher, these areas were sometimes accompanied by tiny (dimensions of 100 microm or less) regions of damaged brain parenchyma. The magnitude of the BBBD was larger with Optison than with Definity at 0.5 MPa (signal enhancement: 13.3% +/- 4.4% vs. 8.4% +/- 4.9%; p = 0.04). In addition, more areas with extravasated erythrocytes were observed with Optison (5.0 +/- 3.5 vs. 1.4 +/- 1.9 areas with extravasation in histology section with largest effect; p = 0.03). We concluded that BBBD is possible using Definity at the dosage of contrast agent and the acoustic parameters tested in this study. The probability for BBBD as a function of pressure amplitude and the type of acute tissue effects were similar to what has been observed using Optison. However, under the experimental conditions used in this study, Optison produced a larger effect for the same acoustic pressure amplitude. PMID- 17337110 TI - Sound fields for coded excitations in water and tissue: experimental approach. AB - Coded ultrasonography is intensively studied in many laboratories due to its remarkable properties, particularly increased penetration depth and signal-to noise ratio (SNR). However, no data on the spatial behavior of the pressure field generated by coded bursts transmissions in the tissue were yet reported. This paper reports the results of investigations of the field structure in water, in degassed beef liver and in pork tissue using four different excitations signals, two and 16 periods sine bursts and sinusoidal sequences with phase modulation using 13-bits Barker code and 16-bits Golay complementary codes. The results of measured pressure field distributions before and after compression were compared with those recorded using short pulse excitation. PMID- 17337111 TI - Feasibility of contrast-enhanced sonography during resection of cerebral tumours: initial results of a prospective study. AB - The aim of this study was to adapt the ultrasonographical techniques developed for brain perfusion imaging to an intraoperative setting for topographic diagnosis of cerebral tumours. During surgery, the patients underwent contrast enhanced ultrasonography (phase inversion harmonic imaging, bolus kinetic, fitted model function). Endocavity curved array (6.5EC10, 6.5 MHz) was used intraoperatively. The ultrasound contrast agent SonoVue (Bracco) was administered IV as a bolus injection. Off-line, time-intensity curves as well as perfusion maps were calculated and parameters such as peak intensity were locally extracted to characterise perfusion. Seven patients with brain tumours of different histologic types were subjected to contrast-enhanced ultrasonography during surgery. Tissue differentiation with contrast agent was superior to conventional B-mode ultrasound imaging. Intraoperative contrast-enhanced ultrasonography enabled visualisation of cerebral tumours in high spatial resolution. PMID- 17337112 TI - Portal diameter in the diagnosis of esophageal varices in 266 cirrhotic patients: which role? AB - The aim was to evaluate the predictability of portal diameter (PD) in the diagnosis of esophageal varices (EV) and of large size EV (F3EV) in a large series of patients with cirrhosis. Two-hundred sixty-six persons with cirrhosis (M:F = 153:113; mean age 65.4 +/- 10 y) were studied by abdominal sonography and upper endoscopy. Portal hypertensive gastropathy (PHG) was found in 16.1% and EV was found in 60.9% of patients. Only Child's class (B vs. A: OR 3.4, p < 0.0001; C vs. A: OR 10.3, p < 0.0001; C vs. B: OR 3.1, p = 0.01) and age (OR 1.04, p = 0.03) were independent predictors of EV, whereas PD was not (p = 0.4). Child's class and age were also the only independent predictors of F3EV. Mean PD showed a slight and not significant increase in PHG patients compared with patients with negative endoscopy, a reduction in F1EV patients and then a progressive increase in F2EV and F3EV patients. Patients with PD <12 mm showed a significantly higher prevalence of F1-F2EV (p < 0.05) and a near-significant lower prevalence of endoscopies negative for EV (p = 0.06) than patients with 12 < or = PD < or = 13 mm. PD was not able to predict EV or F3EV in a large series of patients with cirrhosis. The oscillatory trend of PD, proceeding from patients with negative endoscopy to F3EV patients, seems to indicate that EV may unload portal pressure in the initial phases of portal hypertension. PMID- 17337113 TI - Duty cycle dependence of ultrasound enhanced thrombolysis in a human clot model. AB - Combined ultrasound and tissue plasminogen activator (rt-PA) therapy, or ultrasound enhanced thrombolysis (UET), has been shown to improve recanalization in patients with acute ischemic stroke. We measured the effect of ultrasound duty cycle on the lytic efficacy of 120 kHz UET in an in vitro human clot model. The hypothesis was that an increase in duty cycle increases rt-PA lytic efficacy. Human whole blood clots were exposed to 120-kHz ultrasound and rt-PA for 30 min in human plasma. The duty cycle ranged from 0% to 80%, where 0% represents sham exposure. Clot lytic rate was measured by recording the clot width over time. The clot width after 30 min exposure to rt-PA and ultrasound decreases with increasing duty cycle. The initial lytic rate increased linearly with duty cycle. PMID- 17337114 TI - Prostate cancer distribution in patients diagnosed by transperineal template guided saturation biopsy. AB - OBJECTIVES: To determine the prostate cancer incidence, anatomic distribution, Gleason score profile, and tumor burden in patients diagnosed by transperineal template-guided saturation biopsy (TTSB). MATERIALS AND METHODS: One hundred and two patients underwent TTSB; all but one patient had undergone at least one prior negative TRUS biopsy. Criteria for inclusion included an elevated PSA and/or the diagnosis of ASAP or high-grade PIN on prior biopsy. The prostate gland was divided into 24 regional biopsy locations. The median number of biopsy cores was 50. Multiple clinical parameters were evaluated as predictors for prostate cancer diagnosis. RESULTS: The mean patient age was 64.8 yr with a mean PSA of 9.1 ng/ml and a prostate volume of 78.6 cm(3). On average, patients had undergone 2.1 prior negative TRUS biopsies with a mean of 22.4 core biopsies. Prostate cancer was diagnosed in 43 patients (42.2%) with a Gleason score distribution of 6-9. No anatomic region of the prostate gland was spared of cancer. In patients with prostate cancer, an average of 9.9 cores were involved. In multivariate analysis, prostate volume was the best predictor for prostate cancer diagnosis. CONCLUSIONS: TTBS diagnosed prostate cancer in 42.2% of patients. Considerable anatomic variability in prostate cancer distribution was documented. On the basis of this and other reports, cancer eradication will depend on treatment of the entire prostate gland. PMID- 17337115 TI - Editorial comment on: prostate cancer distribution in patients diagnosed by transperineal template-guided saturation biopsy. PMID- 17337116 TI - Adrenocortical tumorigenesis, luteinizing hormone receptor and transcription factors GATA-4 and GATA-6. AB - Luteinizing hormone (LH/hCG) responsiveness of normal and pathological human adrenal glands as well as the possibility of constitutive expressions of luteinizing hormone receptor (LHR) in adrenal cortex has been reported. Some recent studies showed a correlation between the LHR and abundant GATA-4 expression in both metastasizing and non-metastasizing human adrenocortical tumors, but not in normal adrenals, implicating the putative relevance of LHR and GATA-4 for adrenocortical pathophysiology. However, the physio- and pathophysiological significance of LHR and GATA-4 in the mechanism of adrenocortical tumorigenesis remains unclear. The paucity of suitable models for adrenal tumorigenesis makes the establishment of proper animal models highly important. LHR expression in the murine adrenal gland is an exception and not found in wild-type (WT) animal. We have previously shown that ectopic LHR expression in the murine adrenal gland can be induced by chronically elevated LH levels. We have generated a gonadotropin-responsive adrenal tumor model in gonadectomized transgenic (TG) mice expressing the inhibin alpha promoter/Simian Virus 40 T antigen transgene (inhalpha/Tag). Given the induction of expression and regulation of GATA-4 and GATA-6 zinc finger transcription factors in the gonads by gonadotropins, this review will explore their relationship to LHR expression and their role in adrenocortical tumorigenesis. A functional link between LHR and GATA-4 actions in the adrenal pathophysiology is proposed. PMID- 17337117 TI - Application of MCM-41 for dyes removal from wastewater. AB - The adsorption of three basic dyes (Rhodamine B (RB), Crystal Violet (CV), and Methylene Green (MG)) and two acid dyes (Acid Red 1 (AR1) and Erioglaucine (EG)) onto MCM-41 was studied to examine the potential of MCM-41 for the removal of dyes from water solution. The revolution of pore structure and surface chemical characteristics of MCM-41 induced by dyes adsorption was characterized based on the analyses of XRD patterns, FTIR spectra, and nitrogen adsorption-desorption isotherms. The adsorption capacity of MCM-41 for the five dyes followed a decreasing order of RB>CV>MG>EG approximately AR1. It was experimentally concluded that if the dyes adsorption did not introduce a serious disorder on the pore structure of MCM-41 (such as RB adsorption), MCM-41 might be a good adsorbent for the removal of basic dyes from water solution. The fitness of both Langmuir and Freundlich adsorption model on describing the equilibrium isotherms of three basic dyes was examined. The suitability of both pseudo-second-order kinetic model and the intraparticle diffusion model for the description of the kinetic data was investigated, from which the adsorption mechanism was examined. PMID- 17337118 TI - Product distribution modelling in the thermal pyrolysis of high density polyethylene. AB - The thermal fast pyrolysis of high density polyethylene (HDPE) has been carried out in a conical spouted bed reactor in the 450-715 degrees C range, and individual products have been monitored with the aim of obtaining kinetic data for the design and simulation of this process at large scale. Kinetic schemes have been proposed in order to explain both the results obtained in the laboratory plant and those obtained in the literature by other authors operating at laboratory and larger scale. Discrimination has been carried out based on the contribution of the variance of model parameters (stepwise regression) to the total variance explained by the model. The models based on that of Westerhout et al. [R.W.J. Westerhout, J. Waanders, W.P.M. Van Swaaij, Recycling of polyethene and polypropene in a novel bench-scale rotating cone reactor by high-temperature pyrolysis. Ind. Eng. Chem. Res. 37 (6) (1998) 2293-2300] do not adequately predict the experimental results, especially those corresponding to aromatics and char, which is probably due to the very short residence times attained in the conical spouted bed and, consequently, to the lower yields of aromatics and char. The model of best fit is the one where polyethylene degrades to give gas, liquid (oil) and wax fractions. Furthermore, the latter undergoes secondary reactions to give liquid and aromatics, which in turn produce more char. PMID- 17337119 TI - Granular bed filtration of high temperature biomass gasification gas. AB - High temperature cleaning of producer gas from biomass gasification has been investigated with a granular filter. Field tests were performed for several hours on a single filter element at about 550 degrees C. The results show cake filtration on the granular material and indicate good filtration of the biomass gasification producer gas. The relatively low pressure drop over the filter during filtration is comparable to those of bag filters. The granular filter can operate with high filtration velocities compared to bag filters and maintain high efficiency and a low residual pressure. This work is a part of the BioSOFC-up project that has a goal of utilizing the producer gas from the gasification plant in a solid oxide fuel cell (SOFC). The BioSOFC-up project will continue to the end of 2007. PMID- 17337120 TI - Alpha-synuclein overexpression reduces gap junctional intercellular communication in dopaminergic neuroblastoma cells. AB - Alpha-synuclein has been implicated in the pathology of certain neurodegenerative diseases, including Parkinson disease (PD) and dementia with Lewy bodies (LBs). Overexpression of human alpha-synuclein in neuronal cells reduces cell viability, but the precise cellular and molecular mechanisms remain poorly understood. Gap junctional intercellular communication (GJIC) is thought to be essential for maintaining cellular homeostasis and growth control. In the present study, the effect of alpha-synuclein overexpression on GJIC in human dopaminergic neuroblastoma SH-SY5Y cells was investigated. Cells overexpressing wild-type alpha-synuclein were more vulnerable to hydrogen peroxide and 6-hydroxydopamine. GJIC was decreased in cells overexpressing alpha-synuclein. In addition, alpha synuclein binds directly to connexin-32 (Cx32). As such, the post-translational modification of Cx32 was enhanced in cells overexpressing alpha-synuclein. These findings suggest that alpha-synuclein can modulate GJIC in a dopaminergic neuronal cell line through specific binding to Cx32. PMID- 17337121 TI - Feeding and systemic D-amphetamine increase extracellular acetylcholine in the medial thalamus: a possible reward enabling function. AB - Acetylcholine neurons that project forward from the midbrain are known to enable dopaminergic reward functions in the ventral tegmental area. The question is whether acetylcholine might also be released in the mediodorsal thalamus for the same general purposes. Rats with a microdialysis probe lodged in the mediodorsal thalamus were allowed to eat chow for 20 min after 16-h food deprivation or were given varying doses of D-amphetamine when fed ad libitum. The result in both cases was a significant increase in extracellular acetylcholine. During feeding, acetylcholine increased to 177% of baseline. In response to d-amphetamine (2.5 mg/kg), acetylcholine increased to 184%, and with a higher dose (5 mg/kg) to 400% of baseline. It is concluded that midbrain projections to limbic portions of the thalamus provide acetylcholine for behavioral activation. This cholinergic function theoretically plays a role in enabling the limbic circuits that pass through the thalamus for reinforcement of feeding and psychostimulant abuse. PMID- 17337122 TI - Purification and characterization of a 45-kDa concealed antigen from the midgut membranes of Ornithodoros erraticus that induces lethal anti-tick immune responses in pigs. AB - Ornithodoros erraticus is an argasid tick that can transmit severe diseases such as human relapsing fever and African swine fever. In the search for a vaccine against this parasite, a crude extract of tick midgut membranes (GME) was obtained that in pigs and mice induced a protective response able to kill up to 80% of the nymphs in the first 72 h post-feeding and to reduce the fecundity of females by more than 50%. To identify the protective antigens, the GME was subjected to successive biochemical fractionations and the resulting simpler protein fractions were inoculated in pigs. A 45-kDa antigen, the so-called Oe45, was detected, purified and demonstrated to be responsible for the protection induced by the GME. Oe45 seems to be a membrane protein that is presumably expressed on the luminal membrane of midgut epithelial cells. Oe45 consists of at least two differently charged bands (cationic and neutral), which show antigenic cross-reactivity. The possibility that these bands might be different isoforms of the same protein is discussed. Although Oe45 is constitutively expressed at low levels throughout the trophogonic cycle, its expression is up-regulated by the ingestion of blood, as suggested by the higher levels observed between 6 and 72 h post-feeding. PMID- 17337123 TI - Effects of citalopram treatment on hypothermic and hormonal responses to the 5 HT1A receptor agonist buspirone in patients with major depression and therapeutic response. AB - Serotonin (5-HT) 5-HT1A receptor seems to play an important role in the pathophysiology of major depression and in the mechanism of action of antidepressants. In vivo function of 5-HT1A receptors can be monitored using specific pharmacological challenge tests. The present study aimed at exploring the adaptative 5-HT1A receptor changes in depressed patients before and after 8 week treatment with citalopram. The study population consisted of 30 consecutive outpatients of both sexes aged 18-45 years with major depressive disorders (DSM IV). Basal score in the Hamilton Rating Scale for Depression (HRSD) was higher than 17. Therapeutic response was defined as a 50% decrease in the HRSD score. The hypothermic and endocrine responses (ACTH, cortisol, and prolactin) induced by the 5-HT1A receptor agonist, buspirone (30 mg p.o.) were measured. After 8 weeks on citalopram, the delta max of hypothermic response elicited by buspirone was markedly decreased (p<0.001). Patients showed a decrease in responses to ACTH (delta max p=0.005; AUC p=0.028) and cortisol (delta max p=0.05). However, the prolactin response increased (delta max p=0.02; AUC p=0.005). There was a significant correlation between the therapeutic effect and reductions of ACTH (r=0.883; p<0.001) and cortisol (r=0.610; p=0.001) responses. Changes induced by citalopram support an alteration of 5-HT1A receptors in major depression. A decrease in the overactivity of the HPA axis may be one factor associated with the response to citalopram. PMID- 17337124 TI - Profiling the culprit in Alzheimer's disease (AD): bacterial toxic proteins - Will they be significant for the aetio-pathogenesis of AD and the transmissible spongiform encephalopathies? AB - The aetiology of Alzheimer's disease (AD) and the transmissible spongiform encephalopathies (tSEs) is still elusive. The concept that prion protein (PrP(Sc)) is the aetiological agent (infectious protein) in the tSEs has recently been questioned. In AD, the cause of the aberrant cleavage of the beta-amyloid precursor protein (APP), resulting in the production of amyloidogenic Abeta fragments, has yet remained obscure. Moreover, the amyloid hypothesis of AD has been seriously challenged. In both AD and the tSEs, pathogens of various nature, including bacteria, have been discussed as possible causal factors. However, aetiological considerations have completely neglected microbial products such as the bacterial toxic proteins (BTPs). The present paper is aimed at drawing a "culprit profile" of these toxic molecules that can exert, at low-dosage, neuro degeneration through various effects. Clearly, BTPs may affect cell-surface receptors including modulatory amine transmitter receptor expression, block neuro transmitter release, increase intra-cellular Ca(2+) levels, affect intra-cellular signal transduction, change cyto-skeletal processing, alter synaptic transmission, influence APP proteolysis, interact with cell surface proteins like PrP(C) or their GPI anchors, act as chaperones inducing conformational change in proteins (e.g., PrP(C) to PrP(Sc)), alter lipid membrane integrity by affecting phospholipases or forming pores and channels, induce vacuolar (spongiform) change and elicit inflammatory reactions with cytokine production including cytokines that were demonstrated in the AD brain. Like PrP(Sc), BTPs can be heat-stable and acid-resistant. BTPs can meet the key-proteins of AD and tSEs in the lipid-rich domains of the plasma membrane called rafts. Basically, this might enable them to initiate a large variety of unfavourable molecular events, eventually resulting in pathogenetic cascades as in AD and the tSEs. All in all, their profile lends support to the hypothesis that BTPs might represent relevant culprits capable to cue and/or promote neuro-degeneration in both AD and the tSEs. PMID- 17337125 TI - Path planning in the hippocampo-prefrontal cortex pathway: an adaptive model based receding horizon planner. AB - Four characteristic properties of human path planning strategy are course and fine planning, supervised planning, adaptation and robustness, and complexity reduction. These four characteristics are also observed in "model predictive controller" and its modified version, "receding horizon planner". We hypothesize that the human brain performs path planning tasks, literally like a receding horizon planner. The similarities between human brain and a receding horizon planner are: (1) hippocampus contains the course model and the parietal cortex is responsible for the fine model. (2) Replanning and trajectory tuning using the visual data in parietal cortex and prefrontal cortex is exploited in an adaptive restricted receding horizon. Prefrontal cortex plays the role of the supervisor. (3) Adjusting the sampling time of the planner is implemented based on changes in the complexity of the environment and tasks. This is in fact, the adaptation, which exists both in human behavior and in receding horizon planner. (4) The brain simplifies path-finding problems to reduce computational loads, exactly similar to what engineering controllers intend to do. The visual data is smoothed by clustering of obstacles, before performing any computational task. Finally, we have discussed the consequence of our hypothesis in Alzheimer disease as an optimal planning disorder. Based on some experimental data, Alzheimer patients have a reduced predictive horizon, making the system less robust and exposed to hazardous conditions in sophisticated environments. Patients with mild Alzheimer disease have little trouble with simple optimization problems; working memory of the prefrontal cortex is sufficient for this purpose. However, in complicated tasks, the brain needs huge extended memory. This memory is available through hippocampo-prefrontal pathway, which is to some extent disturbed in Alzheimer patients. We suggest that this fact may be a basis for future experimental diagnosis tests. We predict that Alzheimer patients should have problems with planning for far future; because they have a weak memory, insufficient for heavy optimization tasks, such as moving through moving obstacles in a dynamic environment. Alzheimer disease could be early detected by designing new tests in which the ability of patients to predict the future events is checked. These tests could be accompanied with a multi-step optimization problem. We believe that paying attention to this opinion may provide a good help in diagnosing Alzheimer disease in earlier stages. Surely, experimental studies are needed to validate our hypothesis. PMID- 17337126 TI - Cataract: window for systemic disorders. AB - Cataract is the leading cause of visual handicap throughout the world, and almost all elderly individuals develop lens opacities. Epidemiological studies have shown that nuclear cataracts in young adults are associated with higher mortality. Many cataractogenic stressors induce endoplasmic reticulum (ER) stress, which in turn induces the unfolded protein response (UPR). The UPR can damage or kill a wide range of cell types and may be involved in many human diseases. We hypothesize that a cataract can be considered a window that can indicate the presence of systemic disorders. This is important because cataract is easily detected during a routine ocular examination. The slightest opacity in any region of the lenses, especially in younger patients, may be a sign of systemic disorders. Earlier detection of systemic disorders can save the lives of patients. If our hypothesis is correct, then elimination of known ER/cataractogenic stressors from individuals with cataracts should be the one of the first steps for treatments of the systemic disorders. We discuss the potential risk factors and beneficial effects of removal of such risk factors in patients with early cataracts. All patients with cataract should be referred for comprehensive medical examination. PMID- 17337127 TI - Delayed healing of chronic leg ulcers can result from impaired trafficking of bone marrow-derived precursors of keratinocytes to the skin. AB - In this paper, it is hypothesized that in chronic wounds the process of homing of bone marrow-derived precursors of keratinocytes is disturbed, and that the interaction between cutaneous T-cell attracting chemokine (CTACK/CCL27) and soluble P-selectin glycoprotein ligand-1 (PSGL-1) can be the cause of this impairment. Several studies have revealed that bone marrow-derived cells (BMDC) trans-differentiate into various cellular lineages, and probably they participate also in healing of wounded skin. Recent studies have demonstrated that BMDC can engraft into the epidermis, and probably they do not engraft into epidermis as keratinocyte stem cells, but rather as transient amplifying cells. So, bone marrow-derived keratinocytes build provisional epidermal layer, and later they are replaced by keratinocytes migrating from surrounding skin. Probably after injury BMDC are recruited by pro-inflammatory cytokines, like granulocyte macrophage colony stimulating factor. Further homing to the skin is mediated by CTACK/CCL27. This chemokine is exclusively secreted by keratinocytes. In chronic wounds the recruitment of BMDC seems to be impaired. Inhibition of CTACK/CCL27 by as yet not determined factor could be the cause of delayed healing. PSGL-1 appears to be a good candidate for such inhibiting factor. PSGL-1 is expressed by several populations of leukocytes, and can be released from surface of activated neutrophils. It was demonstrated that soluble PSGL-1 binds CTACK/CCL27, and inhibits chemotaxis mediated by this chemokine. Because there are many activated neutrophils in the wound, it should be expected that wound exudate contains large amount of soluble PSGL-1. Thus, CTACK/CCL27 in the wound would be inhibited, and homing of bone marrow-derived precursors of keratinocytes would be disturbed. If this interaction were found to be the main cause of wound chronicity, above mentioned molecules could be the potential targets for pharmaceutical agents. PMID- 17337128 TI - Bergmann glia as putative stem cells of the mature cerebellum. AB - The adult brain is known to retain a population of stem cells with self-renewing and differentiation ability, which have been identified in two main regions. Recent reports now suggest the presence of such cells in the cerebellum, a part of the CNS which was not formerly thought to harbour stem cells. The precise nature and localisation of these potential new stem cells within the tissue remains unclear, as they have primarily been described at early postnatal stages, before completion of the extensive cell migration accompanying cerebellum maturation. We have shown that a discrete cell population of the cerebellar cortex, the Bergmann glia, shares the expression of key molecular markers with neural stem cells. We examine the hypothesis that the Bergmann glia may represent a novel and abundant stem cell population in the mature cerebellum. PMID- 17337129 TI - Could dynamic attractors explain associative prosopagnosia? AB - Prosopagnosia is one of the many forms of visual associative agnosia, in which familiar faces lose their distinctive association. In the case of prosopagnosia, the ability to recognize familiar faces is lost, due to lesions in the medial occipitotemporal region. In "associative" prosopagnosia, the perceptual system seems adequate to allow for recognition, yet recognition cannot take place. Our hypothesis is that a possible cause of associative prosopagnosia might be the occurrence of Dynamic attractors in the brain's auto-associative circuits. We present a biologically plausible model composed of two stages: Pre-processing and face recognition. In the first stage, the face image is passed through Gabor filters which model the kind of visual processing carried out by the simple and complex cells of the primary visual cortex of higher mammals and the resulting features are fed into a Pseudo-inverse associative neural network for the recognition task. Next, we damage the network by reducing self-connections below a certain threshold in order to create dynamic attractors and hence hinder the networks ability to recognize familiar faces (faces already learned). Results obtained from simulations show that the resulting network responses are very similar to those of associative prosopagnosic patients. We conclude that the problems concerning associative prosopagnosia may partly be explained through the concepts of dynamic attractors. Although there is no known cure for prosopagnosia, we believe that the focus of any treatment should be to help the individual with prosopagnosia develop compensatory strategies for remembering faces. Adults with prosopagnosia as a result of stroke or brain trauma can be retrained to use other clues to identify faces. And a cure for children born with prosopagnosia might eventually rely on reinforcement techniques that reward them for paying attention to faces during early childhood. Reinforcement learning from examples of patterns to be classified using habituation and association would create lower dimensional local basins in the brain, which would form a global attractor landscape with one basin for each face. These local basins would eventually constitute dynamical memories that solve difficult problems in classifying and recognizing faces. PMID- 17337130 TI - Kawasaki disease may be a hyperimmune reaction of genetically susceptible children to variants of normal environmental flora. AB - Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that occurs predominantly in children <5 years of age. For the etiopathogenesis of KD, there is no agreement even as to whether KD is an infectious disease or an immune-mediated disease. The epidemiologic characteristics of KD, including the strict predilection of age in all ethnic groups and the gradually increased incidence after the KD emergence, suggest that KD is affected by the immune maturation in early childhood that may be determined by genetic factors, and KD is also affected by the changed environmental circumstances such as improved public hygiene. We postulated that the pathogenesis of KD is a hyperimmune reaction in genetically susceptible children to the variants of normal flora, which are induced by the environmental factors. Using this hypothesis, we might partly explain the clinical and epidemiological characteristics of KD. We expect that this hypothesis may help to determine the causative agents for KD in the near future. PMID- 17337131 TI - Long-term clinical outcomes of whole-breast irradiation delivered in the prone position. AB - PURPOSE: The aim of this study was to evaluate retrospectively the effectiveness and toxicity of post-lumpectomy whole-breast radiation therapy delivered with prone positioning. METHODS AND MATERIALS: Between September 1992 and August 2004, 245 women with 248 early-stage invasive or in situ breast cancers were treated using a prone breast board. Photon fields treated the whole breast to 46 to 50.4 Gy with standard fractionation. The target volume was clinically palpable breast tissue; no attempt was made to irradiate chest wall lymphatics. Tumor bed boosts were delivered in 85% of cases. Adjuvant chemotherapy and hormonal therapy were administered to 42% and 62% of patients, respectively. RESULTS: After a median follow-up of 4.9 years, the 5 year actuarial true local and elsewhere ipsilateral breast tumor recurrence rates were 4.8% and 1.3%, respectively. The 5-year actuarial rates of regional nodal recurrence and distant metastases were 1.6% and 7.4%. Actuarial disease-free, disease-specific, and overall survival rates at 5 years were 89.4%, 97.3%, and 93%, respectively. Treatment breaks were required by 2.4% of patients. Grade 3 acute dermatitis and edema were each limited to 2% of patients. Only 4.9% of patients complained of acute chest wall discomfort. Chronic Grade 2 to 3 skin and subcutaneous tissue toxicities were reported in 4.4% and 13.7% of patients, respectively. CONCLUSIONS: Prone position breast radiation results in similar long-term disease control with a favorable toxicity profile compared with standard supine tangents. The anatomic advantages of prone positioning may contribute to improving the therapeutic ratio of post-lumpectomy radiation by improving dose homogeneity and minimizing incidental cardiac and lung dose. PMID- 17337132 TI - Intact Mre11/Rad50/Nbs1 complex predicts good response to radiotherapy in early breast cancer. AB - PURPOSE: To investigate the expression and predictive role of the Mre11/Rad50/Nbs1 (MRN) complex and the ataxia-telangiectasia mutated protein (ATM) for the outcome of radiotherapy in breast cancer patients. METHODS AND MATERIALS: The protein expression of ATM and the DNA repair proteins in the MRN complex were investigated using immunohistochemistry in tumors from 224 women with early breast cancer, who were randomized to receive postoperative radiotherapy or adjuvant chemotherapy. RESULTS: Compared with normal breast tissue, the staining intensity of Mre11, Rad50, Nbs1, and ATM was reduced in a majority of the tumors. Weak expression of the MRN complex was correlated with high histologic grade and estrogen receptor negativity (p = 0.01 and p = 0.0001, respectively). Radiotherapy significantly reduced the risk of local recurrence as compared with chemotherapy (p = 0.04). The greatest benefit of radiotherapy was seen in patients with moderate/strong expression of the MRN complex (relative risk = 0.27, 95% confidence interval = 0.098-0.72, p = 0.009), whereas patients with negative/weak MRN expression had no benefit of radiotherapy compared with adjuvant chemotherapy. These results suggest that an intact MRN complex is important for the tumor cell eradicating effect of radiotherapy. CONCLUSIONS: Reduced expression of the MRN complex predicts a poor effect of radiotherapy in patients with early breast cancer. PMID- 17337133 TI - Aromatic plant-derived essential oil: an alternative larvicide for mosquito control. AB - Five aromatic plants, Carum carvi (caraway), Apium graveolens (celery), Foeniculum vulgare (fennel), Zanthoxylum limonella (mullilam) and Curcuma zedoaria (zedoary) were selected for investigating larvicidal potential against mosquito vectors. Two laboratory-reared mosquito species, Anopheles dirus, the major malaria vector in Thailand, and Aedes aegypti, the main vector of dengue and dengue hemorrhagic fever in urban areas, were used. All of the volatile oils exerted significant larvicidal activity against the two mosquito species after 24 h exposure. Essential oil from mullilam was the most effective against the larvae of A. aegypti, while A. dirus larvae showed the highest susceptibility to zedoary oil. PMID- 17337134 TI - Effect of Azadirachta indica leaf methanol extracts on stem cell reproduction. AB - Methanol extracts of Azadirachta indica leaves at concentration from 0.1 to 40 microg/ml showed in vitro an stimulatory activity in stem cell reproduction. These results suggest that the effect of methanol leaf extracts on stem cell reproduction could be of benefit to improve health. PMID- 17337135 TI - Antioxidants do not prevent acrylonitrile-induced toxicity. AB - Several reports have recently described that acrylonitrile (ACN) toxicity resides in its capacity for inducing oxidative stress. ACN can be conjugated with glutathione (GSH), diminishing its cellular content, or being metabolized to cyanide. In the present report, we determine the effect of ACN on the viability of primary-cultured astrocytes as well as the oxidative damage generated by ACN by measuring GSH levels in primary cultured astrocytes. We also analyzed whether the ACN (2.5mM) toxicity could be avoided by using antioxidants such as taurine (5mM), N-acetylcysteine (20 mM), trolox (100 microM), estradiol (10 microM) and melatonin (100 nM-1mM). In this cell culture model, antioxidants were not able to prevent ACN-induced cell damage, with the exception of NAC, confirming that only GSH seems to play a key role in ACN-derived toxicity. Additionally, we measured different parameters of oxidative stress such as catalase activity, lipid peroxidation and GSH concentration, as indicators of the potential oxidative stress mediated by the toxicity of ACN, after exposure of Wistar rats to a concentration of 200 ppm ACN for 14 days. At the concentration assayed, we did not find any evidence of oxidative damage in the brain of ACN-treated rats. PMID- 17337136 TI - Xenogenic oogenesis of chicken (Gallus domesticus) female primordial germ cells in germline chimeric quail (Coturnix japonica) ovary. AB - In present study, chicken primordial germ cells (PGCs) were transferred into quail embryos to investigate the development of these germ cells in quail ovary. Briefly, 2 microl of chicken embryonic blood (stage 14) or about 100 purified circulating PGCs were transferred into quail embryo. Contribution of chicken PGCs were detected in gonads of chimeric quail embryos (stage 28) by immunocytochemical staining of cell surface antigen SSEA-1, and by in situ hybridization (ISH) with female chicken specific DNA probe. As a result, 52.0+/ 43.2 (n=18) and 42.7+/-27.3 (n=17) chicken PGCs were found in the gonads of chimeric quail embryo that was injected with chicken embryonic blood (stage 14) and about 100 purified circulating PGCs, respectively. Furthermore, the ovaries of 81.8% (9/11) 12 days post incubation (dpi) chimeric quail embryos were observed with a mean of 457.6+/-237.1 female chicken PGCs-derived oogonia scattered in ovarian cortex area. In 9 out of 12 newly hatched and one week old chimeric quail chicks, on average of 2883.0+/-1924.1 primary oocytes and 3 follicles derived from chicken PGCs were found, respectively. The present results suggest that chicken female PGCs are able to migrate, colonize, proliferate and differentiate into oogonia, primary oocytes in chimeric quail ovary. PMID- 17337137 TI - Nasal administration of an angiotensin antagonist in the rat model: effect of bioadhesive formulations on the distribution of drugs to the systemic and central nervous systems. AB - The effect of bioadhesive formulations on the direct transport of an angiotensin antagonist drug ((14)C-GR138950) from the nasal cavity to the central nervous system was evaluated in a rat model. Three different bioadhesive polymer formulations (3% pectin LM-5, 1.0% pectin LM-12 and 0.5% chitosan G210) containing the drug were administered nasally to rats by inserting a dosing cannula 7mm into the nasal cavity after which the plasma and brain tissue levels were measured. It was found that the polymer formulations provided significantly higher plasma levels and significantly lower brain tissue levels of drug than a control, in the form of a simple drug solution. Changing the depth of insertion of the cannula from 7 to 15mm, in order to reach the olfactory region in the nasal cavity significantly decreased plasma levels and significantly increased brain tissue levels of drug for the two formulations studied (1.0% pectin LM-12 and a simple drug solution). There was no significant difference between the drug availability for the bioadhesive formulation and the control in the brain when the longer cannula was used for administration. It is suggested that the conventional rat model is not suitable for evaluation of the effects of bioadhesive formulations in nose-to-brain delivery. PMID- 17337138 TI - DSC and EPR investigations on effects of cholesterol component on molecular interactions between paclitaxel and phospholipid within lipid bilayer membrane. AB - Differential scanning calorimetry (DSC) and electron paramagnetic resonance spectroscopy (EPR) were applied to investigate effects of cholesterol component on molecular interactions between paclitaxel, which is one of the best antineoplastic agents found from nature, and dipalmitoylphosphatidylcholine (DPPC) within lipid bilayer vesicles (liposomes), which could also be used as a model cell membrane. DSC analysis showed that incorporation of paclitaxel into the DPPC bilayer causes a reduction in the cooperativity of bilayer phase transition, leading to a looser and more flexible bilayer structure. Including cholesterol component in the DPPC/paclitaxel mixed bilayer can facilitate the molecular interaction between paclitaxel and lipid and make the tertiary system more stable. EPR analysis demonstrated that both of paclitaxel and cholesterol have fluidization effect on the DPPC bilayer membranes although cholesterol has more significant effect than paclitaxel does. The reduction kinetics of nitroxides by ascorbic acid showed that paclitaxel can inhibit the reaction by blocking the diffusion of either the ascorbic acid or nitroxide molecules since the reaction is tested to be a first order one. Cholesterol can remarkably increase the reduction reaction speed. This research may provide useful information for optimizing liposomal formulation of the drug as well as for understanding the pharmacology of paclitaxel. PMID- 17337139 TI - Segmental determination of ethyl glucuronide in hair: a pilot study. AB - Ethyl glucuronide (EtG) is a minor metabolite of ethanol. Its detection in hair is more and more studied in both clinical and forensic context for the purpose of alcohol abuse monitoring. In this pilot study, hair specimens from 15 patients included in a treatment program after alcohol abuse cessation, were segmented and analyzed for EtG. The results were then compared to their self-reported past alcohol consumption and to their blood biomarkers values (GGT, MCV, ASAT, ALAT). EtG concentrations measured in hair varied from 8 to 261 pg/mg. The pattern of EtG concentration detected in the different hair segments matched with the drinking history of patients, displaying variations (increase and decrease) in alcohol consumption and also time of cessation. Results also demonstrated the existence of a significant correlation (r(p)=0.5357; p=0.0390) between EtG concentration in hair and the amount of alcohol intake. Variations in the EtG concentrations with respect to hair segments may provide an overview of the drinking history of patients. Moreover, EtG concentration in hair may help to estimate the daily alcohol intake. PMID- 17337140 TI - Antitumor effects of Nafamostat mesilate on head and neck squamous cell carcinoma. AB - OBJECTIVE: Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, has antitumor activities toward adenocarcinoma, e.g., colon cancer. However, its antitumor effects on other types of cancer have been less extensively studied. We investigated the biological activities of Nafamostat mesilate on cell proliferation, cell-invasive potential and growth factor production in head and neck squamous cell carcinoma (HNSCC). METHODS: Two human HNSCC cell lines established in our department, YCU-L891 and -H891, and a human vulvar squamous cell carcinoma cell line, A431, were examined for the effect of Nafamostat mesilate. The effects on cell growth were evaluated using the MTT assay. The effects on the relative expression levels of mRNA were measured by quantitative RT-PCR. Cytokine secretion was analyzed by enzyme-linked immunosorbent assay. RESULTS: Nafamostat mesilate inhibited the proliferation of two HNSCC cell lines, YCU-L891 and YCU-H891, and A431. In these cell lines, Nafamostat mesilate down regulated both matrix metalloproteinase (MMP)-2 and -9. In addition, it reduced the productions of vascular endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF-beta1) by the tumor cells. CONCLUSION: Our results suggest that Nafamostat mesilate has potential for use as a treatment against local growth, invasion and metastasis of squamous cell carcinoma. PMID- 17337141 TI - Pre-emptive analgesia for removal of nasal packing: A double-blind placebo controlled study. AB - OBJECTIVE: The most frequent complaint of patients after septoplasty is severe pain felt during removal of nasal packing placed on the operation. Various methods have been described to decrease pain and to increase patient comfort during removal of nasal packing. However, these methods are not practical. There has been an increase in the number of studies on pre-emptive analgesia use for postoperative pain relief. The aim of this study was to determine whether pre emptive analgesia decreased pain during removal of Merocel packs placed in septoplasties. METHODS: This is a double-blind randomized, placebo-controlled study. The study included 121 patients who underwent elective septoplasty in our otorhinolaryngology clinic. The patients were randomly assigned into two groups: study and placebo groups. The study and placebo groups received two tablets of diflunisal 500 mg and placebo, respectively, two and a half hours before removal of nasal packing. Visual analog scale (VAS) values immediately after and 5 min after removal of nasal packing, effects of the procedure on patient comfort and its side-effects were evaluated separately. RESULTS: VAS values immediately after the removal of nasal packs significantly decreased in the study group (p<0.001), but there was no significant difference in VAS values obtained after the procedure between the study and placebo groups. Patient discomforts were significantly lower in the diflunisal group (p<0.001). CONCLUSIONS: It can be concluded that pre-emptive analgesia decreases pain during removal of nasal packing placed in septoplasties and increases patient comfort. PMID- 17337142 TI - Laryngeal solitary fibrous tumour. AB - Solitary fibrous tumours (SFT) are rare neoplasms, with an uncommon laryngeal involvement. Only five cases of laryngeal localization have been described in literature. The following is a case of a 75-year-old man with a supraglottic neoplasm of the larynx; after the biopsy immunohistochemical study demonstrated a strong positivity for vimentin, CD34 and Bcl-2. The neoplasm was consequently classified as a SFT. CO(2) laser surgery of the supraglottic larynx, with a wide excision of the neoplasm, was performed. Twenty-four months on, the patient is alive, well and free of disease. Surgical resection is the treatment of choice for laryngeal SFT, but tumour-free resection margins must be achieved to prevent the possibility of local recurrence. Endoscopic resection by means of the CO(2) laser must be accurately planned with MRI or CT imaging to confirm of this kind of surgery. PMID- 17337143 TI - [Incidence and clinical characteristics of symptomatic urinary infections in a geriatric hospital]. AB - OBJECTIVES AND SETTINGS: The authors had for aim to study the incidence of symptomatic urinary infections (SUTI) in elderly patients, to describe their clinical and microbiologic characteristics and first-line treatment in a geriatric hospital with 902 beds: 124 in acute care (ACF), 293 in rehabilitation and intermediate-care (RICF), and 485 in long-term-care-facilities (LTCF). METHOD: During two months in 2003, all positive urine cultures detected by the laboratory were sent to the clinician with a questionnaire on clinical signs, diagnosis of SUTI and antibiotic treatment. RESULTS: SUTI was diagnosed in 85 out of 204 positive urine cultures (40%). The incidence of SUTI was 1.86 per 1,000 patient-days (with rates of 2.63, 2.49, 1.41 per 1,000 patients-days for the ACF, RICF, LTCF respectively). For 51 cases (60%) there were only general symptoms, for 24 cases (28.2%) there were only urinary symptoms, and for 10 cases (11.8%) there were both. Escherichia coli and Proteus mirabilis were the main bacterial species involved in 57 and 14% respectively. E. coli strains were 59% resistant to amoxicillin, 55% resistant to amoxicillin-clavulanic acid, and 39% resistant to fluoroquinolones. The main antibiotics were fluoroquinolones, ceftriaxone, and amoxicillin-clavulanate, prescribed respectively in 52.5, 19, and 9% of the cases. CONCLUSION: SUTI was diagnosed in only in 40% of positive urine cultures from elderly patients hospitalized in our hospital. To improve the management of SUTI in this population, we changed our recommendations for diagnosis and treatment. PMID- 17337144 TI - [Evaluation of antibiotic prophylaxis for hip and knee replacement: a multicentered study in Aquitaine public and private hospitals (SouthWestern France)]. AB - OBJECTIVE: The aim of the study was to estimate the prescription and administration of antibioprophylaxis for hip and knee replacement in Aquitaine (SouthWestern France). METHODS: In 2003, "Social Security" medical experts performed a descriptive and retrospective study on a sample of scheduled surgical operations in all the Aquitaine public and private hospitals. Antibioprophylaxis, protocols, and practice were assessed by studying the patients' medical files. The analysis was made on adjusted numbers to take into account the size of every institution. RESULTS: In 51 hospitals, 58.8% of antibioprophylaxis protocols followed French guidelines. The sample corresponded to an adjusted number of 9,651 patients. Antibiopropylaxis was prescribed for 99.3% of patients, the course of antibioprophylaxis followed guidelines for 77.4% of the patients, the choice of the molecule and the dosage in 85.4% of the cases. Interval between antibiotic injection and surgical section was the main criterion of nonconformity (56.3%); it was under30 minutes for 43.7% of cephalosporin injections. In the post-operative period, administration complied with the medical prescription for 76.4% of the patients and dosage was adapted for 60.0% of the patients. According to the studied variables, 3 to 23.5% of data was missing in the medical files. CONCLUSION: If the quality of care and practice must be improved, it is mandatory to implement written and confirmed antibioprophylaxis protocols, to better document medical files, to insure an improved coordination among professionals before, during, and after surgery. PMID- 17337146 TI - Prognostic values of alpha2-macroglobulin, fibrinogen and albumin in regards to mortality and frailty in old rats. AB - The study aimed to determine if acute phase proteins (APP) are markers of frailty in old rats. We evaluated in male Wistar rats at 96 weeks of age (n=72) whether single measurements of alpha(2)-macroglobulin, fibrinogen and albumin are predictive of mortality, body weight loss and inflammatory status during a 10 week follow-up period. Rats were clustered depending on levels of these APP at baseline. Rats with extremely high levels of alpha(2)-macroglobulin or fibrinogen (upper quartiles), or extremely low level of albumin (lower quartile), had an 11.6, 8.1 and 5.3-fold higher risk of mortality, respectively, than other rats. Body weight loss was negatively correlated with alpha(2)-macroglobulin, a trend was observed with fibrinogen (P=0.08) but not with albumin. Rats with fibrinogen levels >4.0 g/L or alpha(2)-macroglobulin levels >91 mg/L (respective top halves) at 96 weeks of age had higher levels of alpha(2)-macroglobulin and fibrinogen and lower levels of albumin throughout the follow-up period and higher levels of sTNFR-1 and lipopolysaccharide-binding protein at 106 weeks of age. Highest levels of alpha(2)-macroglobulin, fibrinogen and lowest albumin were predictive of mortality, whereas moderate levels of alpha(2)-macroglobulin and fibrinogen were, according to body weight loss and inflammatory status, markers of frailty in old rats. PMID- 17337145 TI - Chronic herpesvirus reactivation occurs in aging. AB - The aged immune system is characterized by clonal expansions of CD8+ T cells of which a substantial portion are directed against Epstein-Barr virus (EBV) and cytomegalovirus (CMV). It is unknown if these expansions represent increased viral reactivation or simply reflect an accumulation over time. We investigated herpesvirus reactivation in young and old subjects co-infected with CMV and EBV. Using molecular and serological techniques, we found significant increases in both the frequency and magnitude of EBV and CMV reactivation in elderly subjects. CMV DNA was frequently detected in the urine of elderly subjects; EBV load in peripheral blood was also significantly increased. Notably, EBV DNA in plasma was detected in a majority of the elderly subjects which was supported by frequent transcription of late structural genes. Furthermore, CD8+ T cells specific for EBV structural antigens were detected in samples from the elderly. Samples from our younger control group were negative for EBV DNA in plasma, CMV DNA in urine, expression of structural transcripts, and lacked CD8+ T cells specific for EBV structural antigens. These findings indicate that the aged immune system is no longer able to control EBV and CMV reactivation that could now be characterized as chronic instead of latent. PMID- 17337147 TI - Ageing reduces the number of vesicular glutamate transporter 2 containing immunoreactive inputs to identified rat pelvic motoneurons. AB - The immunocytochemical localisation of vesicular glutamate transporters, VGLUT1 and VGLUT2, was employed to identify putative glutamatergic axon terminals innervating pelvic motoneurons. VGLUT1 terminals were sparsely distributed within lumbosacral spinal motoneuron pools, including the dorsolateral nucleus, retrodorsolateral nucleus and spinal nucleus of the bulbospongiosus. This was in marked contrast to VGLUT2 which was expressed in a robust innervation of these areas. Retrograde tracing was used to reveal motoneurons innervating the levator ani (LA) muscle. On these neurons, associations with VGLUT2 immunoreactive terminals were abundant while those with VGLUT1 were rare. Ultrastructural investigations revealed that VGLUT2 immunoreactive terminals made asymmetric synaptic contacts with dendrites of retrogradely labelled LA motoneurons. Quantification of VGLUT2 immunoreactive boutons in close association with these dendrites was carried out in young and aged animals using light microscopy. This revealed a significant decline in the numbers of VGLUT2 immunoreactive boutons on the more distal dendrites of motoneurons in aged rats. VGLUT2 boutons were reduced by approximately 21% from 11.25+/-0.5 per 35-mum length of dendrite in young rats to 8.89+/-0.5 in aged animals. This decline in glutamatergic input may reduce the excitability of LA motoneurons and consequently decrease the capacity of the rat to induce reflexive erections. PMID- 17337148 TI - Ultrasonographic changes of major salivary glands in primary Sjogren's syndrome. Evaluation of a novel scoring system. AB - The aim of our study was to determine the reproducibility of a new semi quantitative scoring system based on ultrasonographic (US) evaluation of structural changes of salivary glands in primary Sjogren's syndrome (SS). US evaluation of parotid and submandibular glands was performed in 28 SS patients and 29 control subjects independently by two blinded observers. Echogenicity, delineation of glandular borders and sonographic structure (homogeneity, hypoechoic areas, hyperechoic foci) of salivary glands were semi-quantitatively assessed and the final US score calculated. Inter-observer variability was determined by Cohen's test. A high degree of inter-observer agreement was found regarding the final US score (0.90) and in the assessment of glandular homogeneity (0.90), echogenicity (0.88) and hypoechoic areas (0.88). This study showed good reproducibility of the US evaluation of salivary glands using our novel scoring system. This may have important implications on the diagnostic algorithm in patients with SS. PMID- 17337149 TI - Rodent stroke induced by photochemical occlusion of proximal middle cerebral artery: evolution monitored with MR imaging and histopathology. AB - PURPOSE: To longitudinally investigate stroke in rats after photothrombotic occlusion of proximal middle cerebral artery (MCA) with magnetic resonance imaging (MRI) in correlation with histopathology. MATERIALS AND METHODS: Forty two rats were subjected to photochemical MCA occlusion and MRI at 1.5T, and sacrificed in seven groups (n=6 each) at the following time points: 1, 3, 6 and 12h, and at day 1, 3 and 9. T2-weighted (T2WI) and diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) map was performed in all rats. Contrast-enhanced T1-weighted imaging (CE-T1WI) was compared to intravital staining with Evans blue in one group for assessing blood-brain barrier (BBB) integrity. The brain was stained histochemically with triphenyl tetrazolium chloride (TTC) and processed for pathological assessment. The evolutional changes of relative lesion volume, signal intensity (SI), and the BBB integrity on MRI with corresponding histopathology were evaluated. RESULTS: The ischemic lesion volume reached a maximum around 12h to day 1 as visualized successively by DWI, ADC map and T2WI, implicating the evolving pathology from cytotoxic edema through vasogenic edema to tissue death. The ADC of brain infarction underwent a significant reversion after 12h, reflecting the colliquative necrosis. On CE T1WI, BBB leakage peaked at 6h and at day 3 with a transitional partial recovery around 24h. The infarct volume on T2WI, DWI and ADC map matched well with that on TTC staining at 12h and at day 1 (p>0.05). CONCLUSION: The evolution of the present photothrombotic stroke model in rats could be characterized by MRI. The obtained information may help longitudinal studies of cerebral ischemia and anti stroke agents using the same model. PMID- 17337150 TI - Rapid simultaneous determination for organophosphorus pesticides in human serum by LC-MS. AB - A simple and rapid method was developed for measuring 10 organophosphorus pesticides (acephate, methidathion, dichlorvos, fenthion, EPN, diazinon, phenthoate, malathion, fenitrothion, and cyanophos) in the serum of acute poisoning patients by LC/MS. Following deproteinization by acetonitrile, an aliquot of the biological sample was injected into a C(18) column using 10mM ammonium formate-methanol as the mobile phase. Extraction recoveries were satisfactory and ranged between 60.0 and 108.1% in serum. The limits of detection (LODs) in serum ranged from 0.125 to 1 microg/ml, and the limits of quantitation (LOQs) ranged from 0.25 to 1.25 microg/ml. An excellent linearity was observed for these LOQs up to 8 microg/ml. Intra- and interassay precision and accuracy were satisfactory for most of the pesticides analyzed. In terms of temperature stability, of all the organophosphorus compounds analyzed, dichlorvos and malathion exhibited the most rapid degradations over 24h at room temperature. Methidathion and diazinon remained relatively stable at all temperatures during the entire 4-week testing period. The present method was successfully applied to one actual case of acute poisoning. In conclusion, this method is simple, accurate, and useful for the determination of organophosphorus pesticides and should benefit both clinical and forensic toxicology. PMID- 17337151 TI - Separation and determination of four active components in medicinal preparations by flow injection-capillary electrophoresis. AB - A simple, rapid and accurate method for the separation and determination of paracetamol (Par), pseudoephedrine hydrochloride (Pse), dextromethorphan hydrobromide (Dex) and chlorphenamine hydrogen maleate (Chl) was developed by combination of flow injection and capillary zone electrophoresis for the first time. The analysis was carried out using an unmodified fused-silica capillary (75 mm x 75 microm i.d. x 375 microm o.d., effective separation length of 45 mm) and direct ultraviolet detection at 214 nm, 1.0 kV applied voltage. The optimized running buffer composed of 75 mM sodium borate-15% (v/v) acetonitrile (ACN) (pH* 9.30) was applied for the separation of the four analytes. The separation was achieved in 4.5 min. The sample throughput rate could reach up to 19 h(-1). The repeatability (defined as relative standard deviation) was 0.6%, 1.0%, 2.1%, 1.9% with peak height evaluation and 0.7%, 1.8%, 0.7%, 1.1% with peak area evaluation for Par, Pse, Dex and Chl, respectively. The limits of detection (S/N=3) were 0.22 microg/ml, 0.29 microg/ml, 0.42 microg/ml and 0.70 microg/ml for Par, Pse, Dex and Chl, respectively. The method was successfully applied to determine the four compounds in three cold medicines with recoveries in the range of 97.18 105.15%. PMID- 17337152 TI - Caring for Somali women: implications for clinician-patient communication. AB - OBJECTIVE: We sought to identify characteristics associated with favorable treatment in receipt of preventive healthcare services, from the perspective of resettled African refugee women. METHODS: Individual, in-depth interviews with 34 Somali women in Rochester, NY, USA. Questions explored positive and negative experiences with primary health care services, beliefs about respectful versus disrespectful treatment, experiences of racism, prejudice or bias, and ideas about removing access barriers and improving health care services. Analysis was guided by grounded theory. RESULTS: Qualities associated with a favorable healthcare experience included effective verbal and nonverbal communication, feeling valued and understood, availability of female interpreters and clinicians and sensitivity to privacy for gynecologic concerns. Participants stated that adequate transportation, access to healthcare services and investment in community-based programs to improve health literacy about women's preventive health services were prerequisite to any respectful health care system. CONCLUSION: Effective communication, access to healthcare services with female interpreters and clinicians, and community programs to promote health literacy are themes associated with respectful and effective healthcare experiences among Somali women. PRACTICE IMPLICATIONS: Adequate interpreter services are essential. Patient-provider gender concordance is important to many Somali women, especially for gynecological concerns. PMID- 17337153 TI - Satisfaction with outcome and attitudes towards scarring among women undergoing breast reconstructive surgery. AB - OBJECTIVE: Surgical breast reconstruction following mastectomy often results in scarring not only to the breast but often to the donor-site area. However, few studies have been devoted to the potential effects of scarring among women who underwent breast reconstruction. The aim of the study was to explore these women's attitudes towards scarring. METHOD: Fifteen women who had undergone Transversus Abdominis Myocutaneous (TRAM) flap breast reconstruction surgery (mean age 50 years) took part in a semi-structured qualitative interview. The interview examined their experiences of breast reconstruction surgery, post surgical adjustment and the impact of scarring. RESULTS: Scarring, particularly donor-site scarring, emerged as the main area of dissatisfaction with the breast reconstruction process. Expectations of the surgery and information provided prior to surgery were also found to relate to women' reports of overall satisfaction. CONCLUSION: This study highlighted that satisfaction with breast reconstruction surgery included relief at not needing to wear prostheses and increased body confidence. However, some women reported unrealistic expectations regarding the outcomes of breast reconstruction surgery including extended recovery time and donor-site scarring. PRACTICE IMPLICATIONS: Future patients may therefore benefit from a patient-centred evaluation of their information needs incorporating both their preferences for type and amount of information at each stage of treatment and recovery as well as their understanding and interpretation of the information given to them. PMID- 17337154 TI - Radioiodine ablation of post-surgical thyroid remnants after preparation with recombinant human TSH: why, how and when. AB - AIMS: The use of recombinant human TSH (rhTSH) represents one of the most exciting innovations in the field of differentiated thyroid cancer (DTC) management, but the use of rhTSH for radioiodine post-surgical thyroid remnant ablation is still controversial. The aim of this review is to provide the reader with an analysis of the literature regarding the use of rhTSH for the radioiodine ablation of post-surgical thyroid remnants. METHODS: We performed a literature search of the most relevant papers in the PubMed database. FINDINGS AND CONCLUSIONS: To date, five prospective studies have been published regarding this topic and there is strong evidence of the effectiveness of rhTSH, at least when high doses of 131I are used. Vice-versa, data regarding the outcome of ablation using low doses (30 mCi) are quite different in the studies published. So the problem of the amount of 131I to be administered and the influence of iodine intake is still open. In fact, the results of some studies suggest that 131I uptake could be particularly dependent on iodine intake during the euthyroid state and when low doses of 131I are used. This could be the reason for the reduced radioiodine uptake observed in other studies. However, also when rhTSH stimulation had produced a reduced iodine uptake, this was at least partially compensated for by an increased half-time in thyroid cells. So rhTSH stimulation appears to have pathophysiological bases which all lead to a powerful destructive effect by 131I on thyroid cells. All the data in the literature appear concordant that rhTSH is safe and associated to a good quality of life and the problem of costs appears negligible when compared to the benefits for the patient. In most cases, the use of rhTSH, for radioiodine ablation of post-surgical thyroid remnants can represent the best therapeutic option that we can offer to the patient. PMID- 17337155 TI - [Postoperative pain management on surgical wards in one university hospital: short- and medium-term effects of a quality assurance program]. AB - OBJECTIVES: Evaluation of the short- and medium-term impact of a postoperative pain management quality assurance programme in a university hospital. STUDY DESIGN: Prospective study. MATERIALS AND METHODS: In 1998: chart review and survey of patients and professionals. Principal corrective actions: support for evaluation and tracking of potentially painful surgical procedures, prescription form including an emergency treatment plan, distribution of a set of guidelines. Evaluation was identical during the quality assurance programme and three years later, in 2003. RESULTS: In 2003, information regarding postoperative analgesia was received by 70% of patients and understood by 99% (50% in 1998, p<0.001). Sixty-two percent of patients were totally satisfied with their doctors in 2003 vs 75% in 1998 (NS). Pain was documented in 63.1% of charts in 2003, vs 10% in 1998 (p<0.001). Hundred percent of doctors were aware of the analgesic protocols in 2003 vs 69% in 1998 (p<0.02). In 2003, the treatment of analgesic side effects was known by 86% of doctors vs 29% in 1998 and these effects were looked for by 57% of caregivers in 2003 vs 11% in 1998 (p<0.001). CONCLUSION: Management of postoperative pain has progress significantly and the quality indicators used for evaluation have improved. Patients are better informed, which raises standards. The programme will be extended to all other surgical departments of the hospital, under the authority of CLUDS (Committee for Pain Control and Palliative Care). PMID- 17337156 TI - [Serogroup C meningococcemia presenting as pericarditis in a 55-year-old woman without medical history]. AB - In case of meningococcemia, isolated pericarditis is a rare event with a high mortality rate. We report the clinical and paraclinical signs that lead us to the diagnosis in a 55-year-old woman with favourable evolution. Previously described predisposing factors were no found. PMID- 17337157 TI - [Spontaneous spinal epidural haematoma during pregnancy]. AB - Spontaneous spinal epidural haematomas are quite rare. We report here the case of a 27-year-old woman, without previous history of relevant medical disorder, who presented with acute paraplegia at 36 weeks of gestation. MRI performed in emergency revealed a T8 epidural haematoma. The management consisted in an emergency Caesarean section under general anaesthesia, followed immediately by a T8 laminectomy allowing the spinal cord decompression 14 hours after the first symptoms. Neurologic recovery was rapid and complete, except for bladder dysfunction persisting one month later. Spontaneous spinal epidural haematomas require a prompt diagnosis because neurologic prognosis essentially depends on the interval of time between onset of symptoms and surgical decompression. Obstetrical management especially depends on the term of pregnancy. For the anaesthesiologist, the difficulty is the management of both pregnant condition (full stomach general anaesthesia) and spinal cord compression (maintenance of spinal cord perfusion pression and limitation of ischaemia and oedema). PMID- 17337158 TI - C15orf2 and a novel noncoding transcript from the Prader-Willi/Angelman syndrome region show monoallelic expression in fetal brain. AB - The Prader-Willi syndrome (PWS) region contains several genes transcribed from the paternal chromosome only. We have previously identified a testis-specific gene, C15orf2, which maps between NDN and SNURF-SNRPN and is expressed from both alleles. Here we report on two novel genes (prader-willi region non-protein coding RNA 1 and 2) located between NDN and C15orf2. By database search we found five partially duplicated copies, of which only one of each appears to be active. PWRN2 is expressed only in testis and is biallelic. PWRN1 is biallelically expressed in testis and kidney, but monoallelically in fetal brain. Methylation analysis of a CpG island 15 kb upstream of exon 1 showed absence of methylation in spermatozoa, but methylated and unmethylated alleles in fetal brain. Reinvestigation of C15orf2 revealed that this gene is also expressed in fetal brain and that expression in this tissue is monoallelic. We conclude that PWRN1 and C15orf2 may play a role in PWS. PMID- 17337160 TI - Detection of catechol-O-methyltransferase Val158Met polymorphism by a simple one step tetra-primer amplification refractory mutation system-PCR. AB - The G-->A transition at nucleotide 21881 of the human catechol-O methyltransferase (COMT) gene represents a functional genetic polymorphism (Val158Met), rendering an enzyme with reduced activity that has been associated with psychiatric disorders and estrogen-related cancers. A new method for the detection of this polymorphism is described, based on the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), with a single PCR to discriminate both alleles. Two primers amplify a common amplicon independently of the allele considered. At the same time, two primers are used, differing in the 3' base. In the Val/Val or Met/Met conditions, amplification occurs both in the general amplicon and in the specific allele; in the Val/Met condition three different amplicons are produced. Direct DNA sequencing of a COMT region containing the G/A polymorphism demonstrates the validity of this tetra-primer ARMS-PCR method. Reevaluation by PCR-RFLP revealed 100% accordance for genotype adscription. Subjects carrying the COMT(HH) genotype in a Spanish population comprised 28%, and the COMT(LL) homozygotes amounted to 21%. The described method provides a fast and reliable approach for determining COMT polymorphism that can be useful in large clinical studies using minimal quantity of DNA, avoiding the timely and costly use of restriction enzymes. PMID- 17337159 TI - Use of barusiban in a novel study design for evaluation of tocolytic agents in pregnant and neonatal monkeys, including behavioural and immunological endpoints. AB - The oxytocin receptor antagonist barusiban, currently being developed for treatment of preterm labour, was investigated in pregnant cynomolgus monkeys with a 9-month postnatal follow-up of their offspring. The nature of barusiban, its indication, and the potential exposure of pre- and postnatal infants entailed the design of a unique protocol to investigate all aspects of maternal and offspring well-being. Barusiban was administered to the mothers from gestation day 85 until delivery with daily subcutaneous dosages up to 2.5mg/kg body weight/day. There were no test article-related effects seen in the mothers at any time during the study. The postnatal examination of offspring included routine toxicological parameters, as well as specialised investigation of the immune, cardiovascular, renal and central nervous systems, including a full behavioural assessment. A full pathology examination of offspring was performed at the end of the 9-month postnatal period. No adverse infant findings occurred. PMID- 17337161 TI - Low-density lipoprotein cholesterol in patients treated with atypical antipsychotics: missed targets and lost opportunities. AB - BACKGROUND: The treatment of psychotic disorders with second-generation antipsychotics (SGAs) has been linked to an increased risk of coronary heart disease (CHD). Lowering low-density lipoprotein-cholesterol (LDL-C) to individualized targets of 100, 130 or 160 mg/dl reduces the risk of CHD. We determined the prevalence of above-target LDL-C and its management during psychiatric hospitalization. METHODS: 364 hospitalized adults receiving SGAs underwent LDL-C target assessments. Records of patients with above-target LDL-C were searched for dietary or pharmacologic treatments and referrals for medical consultation. RESULTS: Above-target LDL-C levels were present in 100 (27.5%) patients and were associated with higher total cholesterol, lower high-density lipoprotein cholesterol, older age, higher systolic blood pressure, smoking and male gender (r(2): 0.53; p<0.0001). Only 32.0% of these patients received appropriate interventions during hospital stays of 27.6+/-23.3 days. CONCLUSIONS: A substantial number of SGA-treated patients have above-target LDL-C, but do not receive interventions to reduce the risk of CHD. PMID- 17337162 TI - Effect of antipsychotics on pituitary gland volume in treatment-naive first episode schizophrenia: a pilot study. AB - The objective of this study was to examine the effect of antipsychotics on pituitary volume in schizophrenic subjects. Pituitary volumes were measured in 16 patients with schizophrenia at baseline and 12 months after treatment with an antipsychotic medication using magnetic resonance imaging (MRI). A group of 12 healthy controls was evaluated at baseline and after 12 months. Pituitary volume significantly increased in the schizophrenic subjects after treatment (12% increase). This appeared to be specific to the prolactin-elevating drugs. In controls, pituitary volume did not change significantly (3% decrease). Pituitary volume may be a useful biomarker for treatments that affect neuroendocrine function. PMID- 17337163 TI - Topical antimicrobials in combination with admission screening and barrier precautions to control endemic methicillin-resistant Staphylococcus aureus in an Intensive Care Unit. AB - We aimed to establish whether screening for methicillin-resistant Staphylococcus aureus (MRSA) and body decontamination upon admission to an Intensive Care Unit (ICU), in combination with barrier precautions, reduced rates of MRSA infection acquired on the unit. This was an interrupted time series study employing segmented regression analysis of data collected for all patients admitted to a 16 bed adult ICU over 48 months. Before the intervention (24 months; 1232 patients (44% female)), MRSA was sought from clinical cultures only and positive patients were barrier nursed in isolation. During the intervention (24 months; 1421 patients (54% female)), all ICU patients were screened for MRSA on admission and were barrier nursed in single rooms when established as MRSA-positive; all were given topical nasal anti-MRSA preparations and daily bed baths with 4% chlorhexidine throughout their stay. Changes in the proportion of patients colonised or infected with MRSA in the ICU were assessed. Before the intervention, 193 new MRSA cases (16%) were identified from 1232 ICU admissions; during the intervention, this was reduced to 92 cases (6%) of 1421 admissions. By time series regression analysis, the proportion of patients with MRSA decreased by 11.38% from ca. 15% to ca. 5% (ca. three-fold reduction) (95% confidence interval 3.5-19.3%; P=0.005). Thus, treatment of 11 patients prevented 1 clinical case of MRSA. Mean length of stay decreased significantly (P<0.001). Although MRSA and methicillin-susceptible S. aureus bacteraemia rates dropped, the changes detected were not statistically significant. The proportion of patients with coagulase-negative staphylococcal bacteraemia decreased significantly (P<0.001) and the trend changed from increasing to decreasing (P<0.001), as did the trend in glycopeptide use (P=0.014). An inexpensive and easy to implement intervention to control MRSA in the ICU was highly successful without compromising antimicrobial susceptibility. PMID- 17337164 TI - Duloxetine increases stage 3 sleep and suppresses rapid eye movement (REM) sleep in patients with major depression. AB - Sleep studies in patients with major depression receiving the new selective norepinephrine and serotonin reuptake inhibitor (SNRI) duloxetine are lacking. Therefore, polysomnography in 10 patients with major depression (7 males, 39.9+/ 7.6 years, HAMD-21 score: 23.6+/-5.6) was recorded twice, before and after 7-14 days of treatment with duloxetine. Stage 3 sleep significantly (P<0.01) increased from 21.0+/-10.7 to 37.4+/-20.1 min. Rapid eye movement (REM) latency significantly (P<0.005) increased from 58.5+/-31.1 to 193.6+/-72.6 min. REM sleep significantly (P<0.005) decreased from 94.8+/-34.5 to 51.5+/-42.5 min. These results partly differ from those in healthy subjects receiving duloxetine. PMID- 17337165 TI - Altered benzodiazepine receptor sensitivity in alcoholism: a study with fMRI and acute lorazepam challenge. AB - Previous studies suggested altered sensitivity of the GABA/benzodiazepine receptor system in alcoholic patients. Expanding on these findings, the present functional magnetic resonance imaging (fMRI) study aimed to assess whether a differential modulation of cognitive brain activation by an acute GABAergic drug challenge could be detected in patients with alcoholism. Eight detoxified male patients meeting DSM-IV criteria for alcohol dependence and nine healthy male control subjects were studied with fMRI while performing a 2-back working memory task. The fMRI scans were performed 1 h after intravenous administration of saline and again 1 h after 0.03 mg/kg lorazepam I.V. After saline, a task x group interaction effect with higher task activation in alcoholic patients in the left cerebellum and the right prefrontal cortex emerged. Additionally, a differential task x drug x group interaction was identified in the right cerebellum with more pronounced reduction in cognitive activation after lorazepam in the patient group. A significant correlation between lorazepam sensitivity and duration of alcohol dependence was detected. The present findings are in line with previous studies suggesting disrupted prefrontal-cerebellar activation with potential compensatory hyperactivation of the compromised brain networks in alcoholism. Moreover, the results suggest enhanced responsivity to an acute GABAergic challenge in the right cerebellum with disease-related disruption of cerebellar functional integrity. PMID- 17337166 TI - pH and ionic strength effect on single fibrinogen molecule adsorption on mica studied with AFM. AB - Although several investigations have been reported on the effect of pH or ionic strength on protein adsorption, most of them have been carried out with protein monolayers and not with single molecules. We have used atomic force microscopy to image, in phosphate buffer, single fibrinogen molecules adsorbed on mica and compare the surface coverage at variable pH (7.4, 5.8, 3.5) or ionic strength (15, 150, 500 mM) conditions. The images obtained and the statistical analysis of the surface coverage indicate adsorption enhancement at the IEP of fibrinogen (pH 5.8) and minimum adsorption at pH 3.5. On the other hand, more protein was adsorbed when the salt concentration of the buffer at pH 7.4 was increased from 15 to 150 mM. However, further increase of salt concentration up to 500 mM resulted in decreased adsorption. To confirm the aforementioned results an approaching bare Si(3)N(4) tip was used as an electrostatic analogue to a protein molecule and interaction force curves between it and the substrate were recorded. The results were in consistence with the double layer theory which justifies the screening of electrostatic repulsion as the salt concentration increases. PMID- 17337167 TI - [A febrile stiff neck]. PMID- 17337168 TI - [A case of fatal neonatal Bacillus cereus meningitis]. AB - A fatal case of meningoencephalitis caused by Bacillus cereus, an uncommon but potential pathogen, resistant to most beta-lactam antibiotics, is described in a 28-day old premature neonate. Difficulties for clinical diagnosis and treatment are discussed. A review of the literature (26 published cases) is given. Early diagnosis of neonatal B. cereus infection is crucial as it leads to a standard treatment including vancomycin. PMID- 17337169 TI - Thermal treating as a tool to produce plastic pellets based on Eudragit RS PO and RL PO aimed for tableting. AB - A 3(2) full-factorial design was used for preparation of pellets using extrusion spheronization technique. Independent variables were %ibuprofen (40, 60, 80) and %Eudragit RS PO/RL PO (0, 50, 100). In all formulations 3% w/w PVP K30 and 10% Avicel PH101 were also used. The pellets were cured in oven at 60 degrees C for 24h. The evaluated responses were crushing strength or yield point, elastic modulus and mean dissolution time (MDT) of pellets. The cured pellets were also compressed at 15kN compaction force and then observed under scanning electron microscope. It was shown that the cured pellets containing 40% or 60% drug exhibited a plastic deformation without any fracture under mechanical tests. The curing process resulted in significant decrease in the elastic modulus of the pellets. The SEM of the compressed pellets were also confirmed the plastic behavior of these pellets. The transition of pellet behavior from brittle to plastic upon curing was due to shift of Eudragit structure from glassy to rubbery state which was supported by DSC studies. However pellets with 80% drug showed brittle properties even after curing due to presence of less amount of Eudragit in their structure. Increasing the ratio of Eudragit RS in the pellets decreased the yield point and elastic modulus of cured pellets containing 40% or 60% drug, indicating more plastic behavior of these pellets. This was attributed to lower Tg of Eudragit RS than Eudragit RL. The curing process also retarded drug release from pellets and increased MDT. Increasing the ratio of Eudragit RS in the pellets increased MDT in cured pellets containing 40% or 60% drug but had no effect in pellets with 80% drug. Overall the results of this study revealed that thermal treating is a proper tool to produce plastic ibuprofen pellets based on Eudragit RS PO and Eudragit RL PO. PMID- 17337170 TI - Functional characterization of cell lines for high-throughput screening of human neuromedin U receptor subtype 2 specific agonists using a luciferase reporter gene assay. AB - We developed a functional cell-based high-throughput screening (HTS) assay to identify modulators of the human neuromedin subtype 2 receptor. This assay utilized the signal transduction pathway of hNMU2R, which is positively coupled to adenylyl cyclase and downstream calcium signal pathways. We describe in detail a robust, sensitive, and functional assay for the hNMU2R G-protein-coupled receptor expressed in human embryonic kidney (HEK)-293 cells, whose activity was reflected by a luciferase reporter gene transcriptionally regulated by a 3-repeat serum response element (SRE)-3 repeat multiple response element (MRE)-3 repeat cyclic AMP (cAMP) response element (CRE)-VIP mini promoter. The HEK 293 clonal cell line, stably co-transfected with the 3xSRE/3xMRE/3xCRE/VIP mini promoter driven luciferase and pCDNA3.1-NMU2R plasmid, was selected by active geneticin sulfate and their ability to express luciferase with a forskolin challenge following hNMU plus forskolin, known to activate intracellular signal transduction. Then the cell density, incubation time, dimethyl sulfoxide (DMSO) concentration used to screen the hNMU receptor subtype 2 specific agonist were optimized, and whether intrinsic luminescent substance of extracts isolated from traditional Chinese herbs disturbs luminescence of luciferase expressed in HEK293 cells was considered. The optimal incubation time was found to be between 8 and 9h, the cell density and DMSO concentrations were optimized from 3x10(4) to 6x10(4), and less than 2%, respectively. Our data show that hNMU2R luci-HEK293 cells and their assay exhibit a low background and ideal model for high throughput screening. These results demonstrate that this reporter gene assay is useful for pharmacological analysis, and is amenable to HTS for human NMU2R agonists. PMID- 17337171 TI - Colonic delivery of compression coated nisin tablets using pectin/HPMC polymer mixture. AB - Nisin containing pectin/HPMC compression coated tablets were prepared and their in vitro behavior tested for colonic delivery. Nisin is a 34-amino-acid residue long, heat stable peptide belonging to the group A lantibiotics with wide antimicrobial activity against Gram-positive bacteria. The invention can be useful for treating colonic infectious diseases such as by Clostridium difficile, and also by colonization of vancomycin-resistant enterococci. In this study, each 100mg core tablet of nisin was compression coated with 100% pectin, 90% pectin 10% HPMC, 85% pectin-15% HPMC, 80% pectin-20% HPMC, 75% pectin-25% HPMC, 100% HPMC at a coat weight of 400mg. The concentration and the activity of nisin were quantified using Well Diffusion Agar Assay. Drug release studies were carried out in pH 3.3 buffer solution. System degradation/erosion experiments were carried out in pH 1.2, 3.3, and 6.8 buffers using a pectinolytic enzyme. The biological activity and NMR studies were performed to assess the stability of nisin during the processing and after the in vitro tests. It was found that pectin alone was not sufficient to protect the nisin containing core tablets. At the end of the 6h 40% degradation was observed for 100% pectin tablets. HPMC addition required to control the solubility of pectin, a 5% increase in HPMC ratio in pectin/HPMC mixture provided a 2-h lag time for nisin release. Eighty percent pectin-20% HPMC appeared to be an optimum combination for further evaluation. Tablets maintained their integrity during the 6-h dissolution test, approximating the colon arrival times. Nisin was found to be active/stable during processing and after in vitro tests. Effect of polymer hydration on pectin degradation was found to be crucial for the enzyme activity. Sufficiently hydrated pectin degraded faster. The pectin/HPMC envelope was found to be a good delivery system for nisin to be delivered to the colon. PMID- 17337172 TI - Preparation and antitumor characteristics of PLA/(PEG-PPG-PEG) nanoparticles loaded with camptothecin. AB - Camptothecin (CPT)-loaded nanoparticles were prepared using poly(dl-lactic acid) (PLA) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PEG-PPG-PEG), and examined for particle characteristics, in vitro release, pharmacokinetics and efficacy. The preparative condition, in which the ratio of PLA/PEG-PPG-PEG/CPT was 35/35/4 (w/w/w) and organic solvent (dichloromethane) was evaporated from the emulsion at 18 degrees C, gave the nanoparticles with the diameter of approximately 230nm, fairly high drug content (ca. 1.6% (w/w)) and stable entrapment of the drug, which were used for in vivo studies. After i.v. administration to normal rats, the nanoparticles showed slightly smaller AUC but much larger MRT as compared with CPT solution, and delivered the drug greatly to the surrounding tissues, in particular to the liver. When antitumor effect was examined by i.v. administration to mice bearing sarcoma 180 (S-180) solid tumor, the nanoparticles showed a significant suppression of tumor growth without body weight loss, and their effect was better than that of CPT solution. The PLA/PEG-PPG-PEG nanoparticles were considered potentially useful to enhance the efficacy of CPT, to which the high drug retention in the body and gradual drug release appeared to be importantly related. PMID- 17337174 TI - Co-generation based energy recovery from municipal solid waste integrated with the existing energy supply system. AB - The SISMan (Simple Integrated System Management) decision-aid model is introduced in this paper. The SISMan model is used in a demonstration of evaluating the viability of adding an Energy-from-Waste (EfW) plant to an existing municipal energy supply system. The integrated system utilizes co-generation in heat and electricity production. The evaluation is carried out by calculating the energy and money flows for the integrated system and comparing the results to the original system values. No "competing technologies" to the EfW alternative are presented; the evaluation is carried out simply by comparing the original ("existing") system flows to the integrated system flows. The results show that in certain conditions it is feasible to integrate an EfW plant with the existing municipal energy supply system in Finland. However, the conditions for a viable integration may not be so easy to fulfill. PMID- 17337175 TI - Labor analgesia and cesarean section in women affected by tuberous sclerosis: report of two cases. AB - Tuberous sclerosis is a multi-system disease characterized by the presence of benign growths in many tissues, mostly localized in skin, brain, kidney and lungs. Epileptic seizures and renal hemorrhage are frequent in such patients. Apart from life-threatening hemorrhage after rupture of angiomyolipomatoma, few data are available about anesthetic considerations during pregnancy. We report two cases of pregnant patients with tuberous sclerosis, one scheduled for medical termination of pregnancy at 27 weeks of gestational, the other a cesarean section for breech presentation under general anesthesia. We review and discuss the ability to perform regional anesthesia in each case. PMID- 17337176 TI - Intracranial arachnoid cyst: anaesthetic management in pregnancy. AB - Arachnoid cysts may be intracranial or extracranial in the neuraxis and may present with headache and neurological signs or acutely with rupture and its complications. We report a case of spinal anaesthesia for elective caesarean section in a woman with an intracranial arachnoid cyst of the posterior fossa. We are unaware of any other such case reports published in the English language. PMID- 17337177 TI - Rapid reversal of critical haemodynamic compromise with nitric oxide in a parturient with amniotic fluid embolism. AB - We describe a case of amniotic fluid embolism presenting as cardiovascular collapse during labour. After initial resuscitation and emergency caesarean section, the patient was transferred to the intensive care unit with profound hypoxaemia, a high inotropic drug requirement and severe coagulopathy. A transoesophageal echocardiogram demonstrated acute right ventricular overload, severe pulmonary artery hypertension and marked diastolic dysfunction of the left ventricle secondary to a dilated right ventricle. The introduction of nitric oxide at 40 ppm produced a dramatic improvement in her cardiorespiratory status. Mother and baby both survived with no apparent long term sequelae. PMID- 17337178 TI - Combined spinal-epidural analgesia for labor in a patient with Marfan's syndrome. AB - We report the management of a patient with Marfan's syndrome for labor analgesia and vaginal delivery using a combined spinal-epidural technique. The rapid onset of analgesia for the first stage of labor provided by the intrathecal opioid, combined with the slow and controlled onset of sensory anesthesia and sympathetic block provided by the dilute epidural local anesthetic, may make this technique particularly useful for labor and delivery in patients with Marfan's syndrome. PMID- 17337179 TI - A randomised comparison of a hand-held Neurotip and the Neuropen for assessing loss of touch sensation during spinal anaesthesia for caesarean section. AB - BACKGROUND: With spinal anaesthesia various methods may be used to assess the block to touch. We wished to compare the levels of block assessed using a non standardised, assessor-dependent touch stimulus with those assessed when the same stimulus was applied in a standardised manner independent of the assessor. METHODS: In a double-blind, randomised study the levels of block to touch were assessed by two investigators, one using a hand-held Neurotip tester pin and the other using the same tester pin mounted in a spring loaded system (Neuropen). Both the testing device and the order of testing were randomised between the two observers. The dermatomes were marked on patients' torsos before surgery. RESULTS: Whole group data analysis in a Bland Altman plot demonstrated a median difference of 0 dermatomes between the two methods: the 5th, 25th, 75th, and 95th centiles of agreement being -2, -1, +1, and +2 dermatomes respectively. There were occasional wide differences in levels of block to touch with the Neuropen varying between seven dermatomes rostral to and four dermatomes caudal to the Neurotip. These differences were short-lived and did not affect clinical management. CONCLUSION: When comparing two very similar touch stimuli, one standardised and user-independent and one non-standardised, we observed occasional wide but short lived differences in the assessed levels of block to touch. Although these differences did not affect clinical management, whether more dissimilar touch testing methods might affect clinical management remains to be seen. PMID- 17337180 TI - Use of electrodialysis and reverse osmosis for the recovery and concentration of ammonia from swine manure. AB - This project aimed at producing a concentrated nitrogen fertilizer from liquid swine manure using electrodialysis (ED) and reverse osmosis (RO), as a mean to help resolve the excess nutrient problem faced by many swine producers, and offer an alternative to chemical nitrogen fertilizer production. Different types of ED membranes were evaluated based on the NH4+ transfer rate, current efficiency and membrane stability. A combination of CMB/AMX membranes was retained due to its high NH4+ transfer rate and chemical stability. The maximum total ammonia concentration (NH3-N) achievable by ED was limited by water transport from the manure to the concentrate compartment, and ammonia volatilization (17%) from the open concentrate compartment. Results suggested that, under the conditions of this experiment, a maximum total NH3-N concentration of about 16g/L could be reached with the ED system. An ED concentrate (8.7g/L of total NH3-N) was also fed to TFC-HF reverse osmosis membranes. A mass balance analysis revealed that the RO permeate, which represented 49.6% of the initial volume, contained 8.6% of the ammonia. However, the RO concentrate contained only 66.6% of the initial total NH3-N, suggesting that 21.2% of the ammonia was volatilized during the concentration test with RO membranes. Ammonia concentration in the RO concentrate reached approximately 13g/L, which is similar to the maximum concentration that could be achieved by ED. These results suggest that the use of ED and RO membranes to recover and concentrate ammonia is potentially interesting but the process must include an approach to minimize ammonia volatilization or trap volatilized ammonia. PMID- 17337181 TI - Development and comparisons of efficient gas-cultivation systems for anaerobic carbon monoxide-utilizing microorganisms. AB - We describe a system for the cultivation of gaseous substrate utilizing microorganisms that overcomes some of the limitations of fixed volume culture vessels and the costs associated with sparging. Cali-5-Bond gas-sampling bag was used as the culture vessel. The bags contain approximately six times more mass of CO than the 40 mL vials at 1 atm of pressure and performed equally to the 40 mL vials in terms of their ability to maintain the composition of the gas over extended incubation times. Experiments using Clostridium ljungdahlii and CO as the sole carbon and energy source in both the gas sampling bag cultivation system and the traditional vial system demonstrated that this culture had a 15x increase in optical density in 24 h of incubation. The gas-sampling bags offer a viable alternative to gas sparging while overcoming the limitations of fixed volume culture vessels. PMID- 17337182 TI - Potent and selective xanthine-based inhibitors of phosphodiesterase 5. AB - Inhibitors of PDE5 are useful therapeutic agents for treatment of erectile dysfunction. A series of novel xanthine derivatives has been identified as potent inhibitors of PDE5, with good levels of selectivity against other PDE isoforms, including PDE6. Studies in the dog indicate excellent oral bioavailability for compound 21. PMID- 17337183 TI - Identification of a series of tetrahydroisoquinoline derivatives as potential therapeutic agents for breast cancer. AB - A series of tetrahydroisoquinoline-N-phenylamide derivatives were designed, synthesized, and tested for their relative binding affinities, and antagonistic activities against estrogen receptor (ER). Compound 1f (relative binding affinity, RBA=5) showed higher binding affinity than tamoxifen (RBA=1), a potent ER antagonist and currently being used for breast cancer therapy. Compound 1f also exerted optimal antagonistic activity against ER in reporter and cell proliferation assays. Interestingly, compound 1j, which only has a minor agonistic effect against ER, acted as a progesterone receptor (PR) antagonist and exerted agonistic activity against AP-1 through ER pathway. Our results show that these new compounds can be employed as leading pharmacophore for further development of potent selective ER and/or PR modulators or antagonists. PMID- 17337184 TI - Synthesis of soluble multivalent glycoconjugates that target the Hc region of botulinum neurotoxin A. AB - The design, synthesis, and initial inhibitory studies of di- and tetravalent glycoconjugates that target the heavy chain of botulinum neurotoxin A are reported. PMID- 17337185 TI - beta-Alkylthio indolyl carbinols: potent nonsteroidal antiandrogens with oral efficacy in a prostate cancer model. AB - Through an in vivo screening model, we developed the in vivo SAR of beta alkylthio indolyl carbinols. Through these efforts we identified a compound with potent oral in vivo efficacy in both immature and mature rat prostate weight reduction models and in a murine xenograft prostate cancer model. PMID- 17337186 TI - Synthesis and herbicidal activity of novel pyrazolo[3,4-d]pyrimidin-4-one derivatives containing aryloxyphenoxypropionate moieties. AB - The 6-(4-alkoxycarbonylalkoxy)phenoxy-3-alkylthio(alkylsulfonyl)-1-phenyl-5 (substituted phenyl)pyrazolo[3,4-d]pyrimidin-4-ones 6 and 7 have been synthesized via the tandem aza-Wittig and annulation reactions of the corresponding iminophosphoranes 4, aromatic isocyanates, and substituted phenols 2 in 52-98% yields. Their structures were clearly verified by spectroscopic data (IR, (1)H NMR, (13)C NMR, MS, and elemental analysis or X-ray diffraction crystallography). And the results of preliminary bioassay indicated that these title compounds possess potential herbicidal activity against the root of rape and barnyard grass. PMID- 17337187 TI - Prediction of binding affinities to beta1 isoform of human thyroid hormone receptor by genetic algorithm and projection pursuit regression. AB - Quantitative structure-activity relationship (QSAR) has been applied to a set of thyroid hormone receptor beta(1) (TRbeta(1)) antagonists, which are of special interest because of their potential role in safe therapies for nonthyroid disorders while avoiding the cardiac side effects. Using the calculated structural descriptors by CODESSA program, principal component analysis (PCA) was performed on the whole compounds to assist the separation of the data into the training set and the test set in QSAR analysis. Six molecular descriptors selected by genetic algorithm (GA) were used as inputs for a projection pursuit regression (PPR) study to develop a more accurate QSAR model. The PPR model performs well both in the fitting and prediction capacity. For the test set, it gave a predictive correlation coefficient (R) of 0.9450, root mean square error (RMSE) of 0.4498, and absolute average relative deviation (AARD) of 4.19%, respectively, confirming the ability of PPR for the prediction of the binding affinities of compounds to beta(1) isoform of human thyroid hormone receptor (TRbeta(1)). PMID- 17337188 TI - Methyl spongoate, a cytotoxic steroid from the Sanya soft coral Spongodes sp. AB - A new steroid with an uncommon 21-oic acid methyl ester moiety designated methyl spongoate (1) which exhibited potent cytotoxicity against BEL-7402 tumor cells in vitro has been isolated from the Sanya soft coral Spongodes sp. Its structure was determined by detailed interpretation of spectroscopic data and by comparison with related compounds. PMID- 17337189 TI - The effect of military load carriage on ground reaction forces. AB - Load carriage is an inevitable part of military life both during training and operations. Loads carried are frequently as high as 60% bodyweight, and this increases injury risk. In the military, load is carried in a backpack (also referred to as a Bergen) and webbing, these combined form a load carriage system (LCS). A substantial body of literature exists recording the physiological effects of load carriage; less is available regarding the biomechanics. Previous biomechanical studies have generally been restricted to loads of 20% and 40% of bodyweight, usually carried in the backpack alone. The effect of rifle carriage on gait has also received little or no attention in the published literature. This is despite military personnel almost always carrying a rifle during load carriage. In this study, 15 male participants completed 8 conditions: military boot, rifle, webbing 8 and 16 kg, backpack 16 kg and LCS 24, 32 and 40 kg. Results showed that load added in 8 kg increments elicited a proportional increase in vertical and anteroposterior ground reaction force (GRF) parameters. Rifle carriage significantly increased the impact peak and mediolateral impulse compared to the boot condition. These effects may be the result of changes to the vertical and horizontal position of the body's centre of mass, caused by the restriction of natural arm swing patterns. Increased GRFs, particularly in the vertical axis, have been positively linked to overuse injuries. Therefore, the biomechanical analysis of load carriage is important in aiding our understanding of injuries associated with military load carriage. PMID- 17337190 TI - Are there specific conditions for which expertise in gymnastics could have an effect on postural control and performance? AB - The first aim of this study was to analyse the effect of elite training, linked to expertise, in gymnastics on postural performance and control. For this purpose, body sway of expert gymnasts was compared to other sportsmen, non experts and non-gymnasts, in two different postures: bipedal (easy and unspecific to gymnasts) and unipedal (difficult and fairly specific). The second aim was to compare the groups in the same tasks but in a visual condition for which they were not trained, i.e. with eyes closed. Postural performance was assessed by centre of gravity motion, which was computed from centre of pressure motion, estimating postural control. A significant difference between the two groups was observed for postural performance in the unipedal posture and with eyes open only. Regardless of their posture, the groups were similarly affected by removal of vision. Expertise in gymnastics seemed to improve postural performances only in situations for which their practise is related to, i.e. unipedal with eyes open. These reveal the importance of choosing a relevant postural configuration and visual condition according to the people's training or by extension experience. PMID- 17337191 TI - Synthesis of carbamate derivatives of iejimalides. Retention of normal antiproliferative activity and localization of binding in cancer cells. AB - The syntheses of six iejimalide carbamate derivatives are described. Their biological activity and those of the unmodified iejimalides A and B against breast and prostate cancer cell lines were determined. These results show that the serine hydroxyl group of iejimalides A and B is a permissive site that can be functionalized to form carbamate derivatives without significant loss of normal biological activity. This method of derivatization will be valuable for cellular target identification, mechanism of action studies, and drug development efforts. A fluorescent derivative does not exhibit binding to the cytoskeletal features of cancer cells. PMID- 17337192 TI - A synthetic method for diversification of the P1' substituent in phosphinic dipeptides as a tool for exploration of the specificity of the S1' binding pockets of leucine aminopeptidases. AB - A novel, general, and versatile method of diversification of the P1' position in phosphinic pseudodipeptides, presumable inhibitors of proteolytic enzymes, was elaborated. The procedure was based on parallel derivatization of the amino group in the suitably protected phosphinate building blocks with appropriate alkyl and aryl halides. This synthetic strategy represents an original approach to phosphinic dipeptide chemistry. Its usefulness was confirmed by obtaining a series of P1' modified phosphinic dipeptides, inhibitors of cytosolic leucine aminopeptidase, through computer-aided design basing on the structure of homophenylalanyl-phenylalanine analogue (hPheP[CH(2)]Phe) bound in the enzyme active site as a lead structure. In this approach novel interactions between inhibitor P1' fragment and the S1' region of the enzyme, particularly hydrogen bonding involving Asn330 and Asp332 enzyme residues, were predicted. The details of the design, synthesis, and activity evaluation toward cytosolic leucine aminopeptidase and aminopeptidase N are discussed. Although the potency of the lead compound has not been improved, marked selectivity of the synthesized inhibitors toward both studied enzymes was observed. PMID- 17337193 TI - An efficient synthesis of 3-fluoro-5-thio-xylofuranosyl nucleosides of thymine, uracil, and 5-fluorouracil as potential antitumor or/and antiviral agents. AB - 1,2:5,6-Di-O-isopropylidene-alpha-D-glucofuranose by the sequence of mild oxidation, reduction, fluorination, periodate oxidation, borohydride reduction, and sulfonylation gave 3-deoxy-3-fluoro-1,2-O-isopropylidene-5-O-p toluenesulfonyl-alpha-D-xylofuranose (5). Tosylate 5 was converted to thioacetate derivative 6, which after acetolysis gave 1,2-di-O-acetyl-5-S-acetyl-3-deoxy-3 fluoro-5-thio-D-xylofuranose (7). Condensation of 7 with silylated thymine, uracil, and 5-fluorouracil afforded nucleosides 1-(5-S-acetyl-3-deoxy-3-fluoro-5 thio-beta-D-xylofuranosyl) thymine (8), 1-(5-S-acetyl-3-deoxy-3-fluoro-5-thio beta-D-xylofuranosyl) uracil (9), and 1-(5-S-acetyl-3-deoxy-3-fluoro-5-thio-beta D-xylofuranosyl) 5-fluorouracil (10). Compounds 8, 9, and 10 are biologically active against rotavirus infection and the growth of tumor cells. PMID- 17337194 TI - Applicability of dose conversion coefficients of ICRP 74 to Asian adult males: Monte Carlo simulation study. AB - International Commission on Radiological Protection (ICRP) reported comprehensive dose conversion coefficients for adult population, which is exposed to external photon sources in the Publication 74. However, those quantities were calculated from so-called stylized (or mathematical) phantoms composed of simplified mathematical surface equations so that the discrepancy between the phantoms and real human anatomy has been investigated by several authors using Caucasian-based voxel phantoms. To address anatomical and racial limitations of the stylized phantoms, several Asian-based voxel phantoms have been developed by Korean and Japanese investigators, independently. In the current study, photon dose conversion coefficients of ICRP 74 were compared with those from a total of five Asian-based male voxel phantoms, whose body dimensions were almost identical. Those of representative radio-sensitive organs (testes, red bone marrow, colon, lungs, and stomach), and effective dose conversion coefficients were obtained for comparison. Even though organ doses for testes, colon and lungs, and effective doses from ICRP 74 agreed well with those from Asian voxel phantoms within 10%, absorbed doses for red bone marrow and stomach showed significant discrepancies up to 30% which was mainly attributed to difference of phantom description between stylized and voxel phantoms. This study showed that the ICRP 74 dosimetry data, which have been reported to be unrealistic compared to those from Caucasian based voxel phantoms, are also not appropriate for Asian population. PMID- 17337195 TI - Does diabetes mellitus target motor neurons? AB - A pattern of peripheral neurodegeneration occurs in chronic diabetes mellitus in which an early, but selective retraction of distal axons may occur prior to any irretrievable neuronal loss. Clinical observations suggest that sensory systems undergo damage before those of motor neurons. In this work, we examined the fate of the spinal motor neuron in a long-term chronic model of experimental (streptozotocin-induced) diabetes already known to be associated with substantial loss of sensory neurons. The integrity, physiological function, and critical forms of protein expression of the full motor neuron tree was examined in mice exposed to 8 months of diabetes. Motor neurons developed progressive features of distal loss of axonal terminals but without perikaryal dropout, indicating distal axon retraction. While numbers and caliber of motor neuron perikarya and their nerve trunk axons were preserved, axons developed conduction velocity slowing, loss of motor units and neuromuscular junctions, and compensatory single motor unit action potential enlargement. Four critical proteins directly linked to diabetic complications were altered in motor neurons of diabetic mice: an elevated perikaryal expression of RAGE and PARP, molecules associated with cellular stress, along with concurrent rises in HSP-27 and pAKT, molecules alternatively identified with neuroprotective survival. Moreover, Akt mRNA was increased in diabetic lumbar spinal cords. Overall these findings indicate that although motor neurons are resistant to irretrievable dropout, they are targeted nonetheless by diabetes and gradually withdraw their terminals from distal innervation. PMID- 17337196 TI - Neuroprotective effect of adult hematopoietic stem cells in a mouse model of motoneuron degeneration. AB - Degenerative spinal motor diseases, like amyotrophic lateral sclerosis, are produced by progressive degeneration of motoneurons. Their clinical manifestations include a progressive muscular weakness and atrophy, which lead to paralysis and premature death. Current pharmacological therapies fail to stop the progression of motor deficits or to restore motor function. The purpose of our study was to explore the possible beneficial effect of mouse adult hematopoietic stem cells (hSCs) transplanted into the spinal cord of a mouse model of motoneuron degeneration. Our results show that grafted hSCs survive in the spinal cord. In addition, the number of motoneurons in the transplanted spinal cord is larger than in non-transplanted mdf mice at the same spinal cord segments and importantly, motor function significantly improves. These effects can be explained by the increased levels of glial cell line derived neurotrophic factor (GDNF) around host motoneurons produced by the grafted cells. Thus, these experiments demonstrate the neuroprotective effect of adult hSCs in the model employed and indicate that this cell type may contribute to ameliorating motor function in degenerative spinal motor diseases. PMID- 17337197 TI - Atrial fibrillation after non-cardiac surgery: P-wave characteristics and Holter monitoring in risk assessment. AB - BACKGROUND: We investigated the role of 12-lead ECG P-wave duration and dispersion and of Holter monitoring as predictors of post-thoracic surgery atrial fibrillation. METHODS: One hundred and five consecutive patients (88 males-17 females; age 60+/-9), undergoing thoracic surgery at National Cancer Institute between 2001 and 2003, were enrolled and both standard ECG and Holter monitoring were obtained from each patient. P-wave study was made on a magnified ECG paper copy. Holter monitoring was performed 1-3 days before surgery; patients were divided into three classes according to number and complexity of premature supra ventricular complexes (0: <30/h and no repetitive forms; 1: >30/h or couplets; 2: run of supraventricular tachycardia or atrial fibrillation). RESULTS: Atrial fibrillation was detected in 12 patients (11%) within 96 h from surgery. In univariable logistic model, P-wave duration was not associated with postoperative atrial fibrillation while P-wave dispersion and Holter monitoring demonstrated a statistically significant association with the occurrence of atrial fibrillation (OR of 30 vs 20 ms=2.06; CI: 1.17-3.64; p=0.012, OR of class 1-2 vs class 0=8.16; CI: 2.04-35.59; p=0.003, respectively). In the multivariable model, both P-wave dispersion and Holter were shown to be significantly associated with the end point. Holter monitoring enhanced the predictive ability of P-wave dispersion (area under the ROC curve increased from 0.64 to 0.80). CONCLUSIONS: P-wave dispersion, but not duration, was associated with atrial fibrillation after thoracic surgery. Preoperative Holter monitoring adds further information and could be used to enhance the P-wave predictive power. PMID- 17337198 TI - Clinical advantages of using mini-bypass systems in terms of blood product use, postoperative bleeding and air entrainment: an in vivo clinical perspective. AB - OBJECTIVE: In an effort to minimize the effect of extracorporeal circulation (ECC), mini-bypass is gaining clinical acceptance in routine coronary artery bypass grafting (CABG). These small circuits target combine the clinical advantages of reduced prime, 100% bio-coating and suction blood separation. We demonstrate that the use of mini-bypass in routine CABG reduces homologous blood product use and postoperative bleeding. Our goal was to also demonstrate that these small systems are effective in gaseous microemboli (GME) management as compared to a conventional extracorporeal system. METHODS: Prospective, randomized study comparing 30 mini-bypass (Dideco ECC.O) to 30 conventional systems (n=30, Dideco 903 Avant). Study included CABG cases only, independent of preoperative coagulative status; clinic ethical committee approval and informed patient consent was obtained before initiating study. RESULTS: There were no statistical differences in terms of patient demographics. Statistically significant differences were seen in transfusion frequency (27% of the study group vs 43% in the control group, p=0.05), transfused volume (133.3+/-244.5 ml vs 325+/-483.1 ml, p<0.05), fresh frozen plasma (0 unit vs 3 units, p<0.001), postoperative bleeding (301.8+/-531.9 ml vs 785.5+/-1000.4 ml, p<0.05) and GME activity post-arterial filter (0.14 microl vs 5.32 microl, p<0.05). CONCLUSIONS: The adoption of mini-bypass significantly potentially reduces hemodilution, donor blood usage, postoperative bleeding and exposure to GME in routine CABG patients as compared to the use of conventional extracorporeal circulation circuits. PMID- 17337199 TI - Traumatic free wall and ventricular septal rupture - 'hybrid' management in a child. AB - A 8-year-old boy showed a traumatic ventricular septal rupture following a blunt chest trauma, and was scheduled for elective catheter closure. Two weeks later, a follow-up echocardiogram revealed a pseudoaneurysm of the anterior wall of the left ventricle. Because of the apical location of the VSD, it was decided to proceed with transcatheter occlusion. After successful VSD closure, the patient was taken to the operation room for surgical repair of the left ventricular pseudoaneurysm. Symptoms and signs seen in patients with ventricular pseudoaneurysms appear to be discrete and variable, and a high clinical index of suspicion with a very close echocardiographic follow-up is strongly recommended after occurrence of a blunt cardiac trauma. The combined 'hybrid' approach of transcatheter closure of the intraventricular rupture followed by surgical closure of the pseudoaneurysm allows for a less invasive and efficient management of this rare combination of post-traumatic ventricular free wall and septal rupture in a child. PMID- 17337200 TI - Lung hernia after video-assisted thoracoscopic lobectomy clearly visualized by three-dimensional computed tomography. PMID- 17337201 TI - Case-control study between extrapleural pneumonectomy and radical pleurectomy/decortication for pathological N2 malignant pleural mesothelioma. AB - OBJECTIVE: To compare the outcomes of extrapleural pneumonectomy (EPP) and radical pleurectomy/decortication (P/D) for N2 malignant pleural mesothelioma (MM). PATIENTS AND METHODS: In a retrospective case-control study we analysed the results of the 57 patients [49 male and 8 female, median age 59 (range 14-70) years] who underwent radical surgery for MM found to have pathological N2 disease over a 7-year-period. EPP was performed on 45 and P/D on 12 patients. Prognostic factors, postoperative course, pathological data and postoperative survival were analysed. RESULTS: Those in the P/D group were significantly older (median age 62 vs 58 years, p=0.03) than in the EPP group. There was no difference in postoperative hospital stay (p=0.1) nor T stage (p=0.7) between the groups. There were no significant differences in the proportion of patients undergoing some adjuvant therapy in each group (p=0.2). Mean survival from diagnosis was 15 months in the EPP group and 16 months for those who underwent P/D (p=0.4). CONCLUSIONS: Preservation of the lung during radical surgery for N2 MM does not compromise survival even in an older group population. We therefore now have ceased to perform EPP in cases of N2 disease and we make every effort to accurately stage patients with mediastinoscopy to identify them. PMID- 17337203 TI - Combined MMF and insulin therapy prevents renal injury in experimental diabetic rats. AB - Conventional therapies for diabetic mellitus are not effective in preventing the progression from early diabetic nephropathy (DN) to end-stage renal disease. The role of inflammation in the pathogenesis of DN has been implicated both clinically and experimentally, which provides an alternative therapeutic target for DN. Anti-inflammatory impact of mycophenolate mofetil (MMF) alone and in combination with insulin had been observed in a rat model of experimental DN. In this study, the diabetic rats were subjected to different treatments. Compared to control, the expression levels of CD68, NGF, and NF-kappaB p65, as determined immunohistochemically, were elevated in diabetic rats. Treatment with combined MMF/insulin is associated with a significant reduction in renal tissue of NGF and NF-kappaB p65 expression, macrophage infiltration. It also partially improved the renal function and attenuated renal hypertrophy at early stage of DN. CD68 was found to positively correlate with urinary albumin excretion and NGF. The combined use of MMF/insulin seemed to offer more protections in rats with experimental diabetic renal injury, and the protective effects of MMF might be due to its anti-inflammatory actions through inhibition of NF-kappaB activation and reduction of T cells and macrophage infiltration and/or other kidney chemokine productions. PMID- 17337204 TI - Stress-induced changes in neuronal Aquaporin-9 (AQP9) in a retinal ganglion cell line. AB - The water channel, Aquaporin-9 (AQP9) is enriched in selected neuronal populations and is unique its ability to act as a lactate-glycerol channel supplying neurons with alternative fuel under ischaemic conditions. AQP9 was detected in RGC-5 cells, a retinal ganglion cell-line, primary RGCs, and retina by Western blotting, real-time PCR (RT-PCR) and immunohistochemistry. RGC-5 cells subjected to a hypotonic stress increased their cell volume that was blocked by known inhibitor of AQP9 (phloretin (40 microM)). RGC-5 cells subjected to hypoxia, showed an up-regulation in AQP9 expression as judged by Western blotting and RT-PCR. Similarly, hypotonic shock (50%) increased AQP9 expression as determined by RT-PCR. AQP9 is involved in energy balance as a glycerol-lactate channel and also appears to regulate cell volume in retinal ganglion neurons. This water channel may play a key role in retinal ganglion pathology. PMID- 17337205 TI - Evaluation of the saccharide content and stability of the first WHO International Standard for Haemophilus influenzae b capsular polysaccharide. AB - Haemophilus influenzae b conjugate vaccines (Hib) are almost entirely evaluated by physico-chemical methods to ensure the consistency of manufacture of batches. As different assays are employed for the quantification of Hib capsular polysaccharide PRP (polyribosyl ribitol phosphate; 5-D-ribitol-(1-->1)-beta-D ribose-3-phosphate) in final formulations and bulk components, there was deemed a need for an International Standard of Hib PRP polysaccharide to be made available. Ten laboratories from 8 different countries participated in a collaborative study to determine the PRP content and assess the suitability of a candidate International Standard PRP preparation (02/208). The results illustrate that a reduction in between-laboratory variability could be achieved by use of a common reference preparation and data analysis showed no significant differences in the values obtained by the different assays: ribose, phosphorus, and high performance anion exchange chromatography-pulsed amperometric detection (HPAEC PAD), suggesting the suitability of the proposed reference for use across these assays for quantification of PRP content in Hib vaccines. On the basis of the results of this study, the First International Standard for PRP, NIBSC Code 02/208, has been established by the Expert Committee of Biological Standards of the World Health Organisation, with a content of 4.933+/-0.267mg/ampoule, as determined by the ribose assays carried out by 7 of the participating laboratories. PMID- 17337206 TI - Large scale production of Bacillus thuringiensis PS149B1 insecticidal proteins Cry34Ab1 and Cry35Ab1 from Pseudomonas fluorescens. AB - The 14kDa (Cry34Ab1) and 44kDa (Cry35Ab1) binary insecticidal proteins are produced naturally by Bacillus thuringiensis PS149B1 as parasporal inclusion bodies. Here, we show production of these two insecticidal proteins in recombinant Pseudomonas fluorescens and their subsequent purification to near homogeneity to provide large quantities of protein for safety-assessment studies associated with the registration of transgenic corn plants. The gene sequence specific for each protein was expressed in P. fluorescens and fermented at the 75 L scale. For Cry34Ab1, the protein accumulated as insoluble inclusion bodies, and was purified by extraction directly from the cell pastes at pH 3.4 with a sodium acetate buffer, selective precipitation at pH 7.0, and differential centrifugation. For Cry35Ab1, the protein was extracted from the purified inclusion bodies with sodium acetate buffer (pH 3.5) containing 0.5M urea, followed by diafiltration. No chromatography steps were required to produce over 30g of lyophilized protein powder with purity greater than 98%, while retaining full insecticidal activity against Western corn rootworm larvae. The proteins were further characterized to assure identity and suitability for use in safety assessment studies. PMID- 17337207 TI - Expression, purification and crystallization of human CD5 domain III, a nano scale crystallization example. AB - The human lymphocyte receptor CD5, a key regulator of immune responses, is involved in the modulation of antigen specific receptor-mediated T cell activation and differentiation signals. CD5 is a membrane glycoprotein which belongs to the group B scavenger receptor cysteine-rich (SRCR) superfamily for which no structural information is available. The most conserved membrane proximal SRCR domain of CD5 (domain III) has been expressed in HEK-EBNA-293 cells. Although the yield of the purified protein was at the level of micrograms, well diffracting crystals have been obtained. The crystals belong to a tetragonal space group P4(1)22 or P4(3)22. They contain two molecules per asymmetric unit and diffracted to 2.5A resolution using synchrotron radiation. The strategy shown here to produce, isolate and crystallize CD5 domain III can be used for other mammalian proteins difficult to produce for structural or other biophysical studies. PMID- 17337208 TI - Protective efficiency of DNA vaccination in Asian seabass (Lates calcarifer) against Vibrio anguillarum. AB - Vibriosis is one of the most prevalent fish diseases caused by bacteria belonging to the genus Vibrio. Vibriosis caused by Vibrio anguillarum produces a 38-kDa major outer membrane porin protein (OMP) for biofilm formation and bile resistant activity. The gene encoding the porin was used to construct DNA vaccine. The protective efficiency of such vaccine against V. anguillarum causing acute vibrio haemorrhagic septicaemia was evaluated in Asian seabass (Lates calcarifer Bloch), a common species of the Indian coast and a potential resource for the aquaculture industry. In vitro protein expression of porin gene was determined by fluorescent microscopy after transfection of seabass kidney cell line (SISK). Fish immunized with a single intramuscular injection of 20 microg of the OMP38 DNA vaccine showed significant serum antibody levels in 5th and 7th weeks after vaccination, compared to fish vaccinated with the control eukaryotic expression vector pcDNA3.1. Asian seabass vaccinated with the OMP38 DNA vaccine was challenged with pathogenic V. anguillarum by intramuscular injection. A relative percent survival (RPS) rate of 55.6% was recorded. Bacterial agglutination and serum complement activity was analysed by using DNA vaccinated seabass serum above 80% of analysed strain was killed at the highest agglutination titre. Histopathological signs of V. anguillarum challenged fish were observed in around 45% of pVAOMP38, 90% of PBS and 87% of pcDNA3.1-vaccinated control fish. The results indicate that L. calcarifer vaccinated with a single dose of DNA plasmid encoding the major outer membrane protein shows moderate protection against acute haemorrhagic septicaemia and mortality by V. anguillarum experimental infection. PMID- 17337209 TI - Immune responses and gene expression in white shrimp, Litopenaeus vannamei, induced by Lactobacillus plantarum. AB - The total haemocyte counts, phenoloxidase (PO) activity, respiratory bursts, superoxide dismutase (SOD) activity, and phagocytic activity and clearance efficiency to Vibrio alginolyticus, as well as prophenoloxidase (proPO), lipopolysaccharide- and beta-1,3-glucan-binding protein (LGBP), serine protein (SP), and peroxinectin (PE) mRNA transcription of L. vannamei, and its susceptibility to V. alginolyticus when the shrimp were fed diets containing Lactobacillus plantarum at 0 (control), 10(7), and 10(10) cfu (kg diet) (-1) for 48 and 168 h were evaluated. The results indicated that PO activity, SOD activity, clearance efficiency to V. alginolyticus, proPO and PE mRNA transcription, and the survival rate after challenge with V. alginolyticus all significantly increased, but the total haemocyte counts significantly decreased in shrimp fed a diet containing Lac. plantarum at 10(10) cfu (kg diet) (-1) for 168 h. However, no significant differences in phagocytosis, LGBP, or SP mRNA expression of shrimp were observed among the different treatments. It was concluded that administration of Lac. plantarum in the diet at 10(10) cfu (kg diet) (-1) induced immune modulation and enhanced the immune ability of L. vannamei, and increased its resistance to V. alginolyticus infection. PMID- 17337210 TI - Transcriptome analysis of gills from the white shrimp Litopenaeus vannamei infected with White Spot Syndrome Virus. AB - We report the analysis of 872 cDNA clones from a WSSV-infected white shrimp Litopenaeus vannamei gill cDNA library. Comparison against the GenBank protein and nucleotide sequences identified 87% (E < or = 10(-2)) as previously known genes, while 13% are novel sequences. The 601 ESTs (87%) represent transcripts of 276 genes. These genes were categorized into 12 groups according to their functions. The more abundant categories were (1) ribosomal proteins (21%), (2) WSSV transcripts and sequences without homology to proteins deposited in the non redundant database (15%), (3) hypothetical proteins (12%) which include genes never described in shrimp and (4) metabolism related proteins (9%). We also found genes involved in stress and immune response; and only one involved in ion transport. Full-length sequences of keratinocyte associated protein 2 (KCP2), selenoprotein M (SelM), chicadae, prohibitin and oncoprotein nm23 are reported. Their mRNAs steady state levels in addition to ferritin, changed at different times post-WSSV infection as estimated by RT-PCR. These results suggest that WSSV alters gene expression in gills and has led to the identification of novel white shrimp specific genes. PMID- 17337211 TI - The influence of crank configuration on muscle activity and torque production during arm crank ergometry. AB - This study investigated the effect of crank configuration on muscle activity and torque production during submaximal arm crank ergometry. Thirteen non specifically trained male participants volunteered. During the research trials they completed a warm-up at 15W before two 3-min exercise stages were completed at 50 and 100W; subjects used either a synchronous or asynchronous pattern of cranking. During the final 30-s of each submaximal exercise stage electromyographic and torque production data were collected. After the data had been processed each parameter was analysed using separate 2-way ANOVA tests with repeated measures. The activity of all muscles increased in line with external workload, although a shift in the temporal pattern of muscle activity was noted between crank configurations. Patterns of torque production during asynchronous and synchronous cranking were distinct. Furthermore, peak, minimum and delta (peak-minimum) torque values were different (P<0.05) between crank configurations at both workloads. For example, at 100W, peak torque using synchronous [19.6 (4.3) Nm] cranking was higher (P<0.05) compared to asynchronous [16.8 (1.6) Nm] cranking. In contrast minimum torque was lower (P<0.05) at 100 W using synchronous [4.8 (1.7)Nm] compared to asynchronous [7.3 (1.2)Nm] cranking. There was a distinct bilateral asymmetry in torque production during asynchronous cranking with the dominant transmitting significantly more force to the crank arm. Taken together, these preliminary data demonstrate the complex nature of muscle activity during arm crank ergometry performed with an asynchronous or synchronous crank set-up. Further work is required to determine how muscle activity (EMG activity) and associated patterns of torque production influence physiological responses and functional capacity during arm crank ergometry. PMID- 17337212 TI - Paranoid delusions and threatening hallucinations: a prospective study of sleep paralysis experiences. AB - Previously we reported a three-factor structure for hallucinations accompanying sleep paralysis (SP). These earlier analyses were, however, based on retrospective accounts. In a prospective study, 383 individuals reported individual episodes online providing further evidence for the three-factor structure as well as clearer conceptually meaningful relations among factors than retrospective studies. In addition, reports of individual episodes permitted a more fine-grained analysis of the internal structure of factors to assess predictions based on the hypothesis that a sensed or felt presence (FP) is a core experience affecting other SP hallucinations. Results were generally consistent with this hypothesis. In particular, associations among, and temporal stability of, sensory hallucinations were largely explained by their common association with FP. The findings are consistent with REM initiation of a threat activated vigilance system with pervasive effects on the SP experience and suggest a potential model for the thematic organization of nightmares and dreams more generally. PMID- 17337213 TI - Transcranial direct current stimulation: a computer-based human model study. AB - OBJECTIVES: Interest in transcranial direct current stimulation (tDCS) in clinical practice has been growing, however, the knowledge about its efficacy and mechanisms of action remains limited. This paper presents a realistic magnetic resonance imaging (MRI)-derived finite element model of currents applied to the human brain during tDCS. EXPERIMENTAL DESIGN: Current density distributions were analyzed in a healthy human head model with varied electrode montages. For each configuration, we calculated the cortical current density distributions. Analogous studies were completed for three pathological models of cortical infarcts. PRINCIPAL OBSERVATIONS: The current density magnitude maxima injected in the cortex by 1 mA tDCS ranged from 0.77 to 2.00 mA/cm(2). The pathological models revealed that cortical strokes, relative to the non-pathological solutions, can elevate current density maxima and alter their location. CONCLUSIONS: These results may guide optimized tDCS for application in normal subjects and patients with focal brain lesions. PMID- 17337214 TI - Oscillatory MEG response to human locomotion is modulated by periventricular lesions. AB - Veridical processing of biological movement is of immense value for adaptive behavior and social communication. Here we ask whether and, if so, how oscillatory cortical magnetoencephalographic (MEG) response to biological motion is modulated by early damage to periventricular regions that might affect the pathways interconnecting subcortical structures with cortex and cortico-cortical connectivity. The visual sensitivity to biological motion was lower in adolescents with periventricular leukomalacia (PVL). In controls, the evoked oscillatory MEG response (26.5 Hz) to biological motion peaked at a latency of 170 ms over the right temporo-parietal cortex. This increase was absent in PVL patients. By contrast, peaks in the oscillatory response to biological motion of lower frequency (23.5 Hz) were found in PVL patients later, at a latency of 290 ms over the left temporal region. The findings provide the first evidence for modulation of oscillatory cortical activity by periventricular lesions. The data suggest that PVL affects the brain connectivity with the right temporo-parietal cortex leading to disintegration of the neural network engaged in biological motion processing. PMID- 17337215 TI - Glucosamine promotes chondrogenic phenotype in both chondrocytes and mesenchymal stem cells and inhibits MMP-13 expression and matrix degradation. AB - OBJECTIVES: Glucosamine (GlcN), a natural amino monosaccharide, is a constituent of glycosaminoglycans (GAGs) found in hyaline cartilage. GlcN salts constitute a new class of nutraceutical components with putative chondroprotective activity, which may target chondrocytes as well as chondroprogenitors cells, such as mesenchymal stem cells (MSCs), during cartilage turnover and repair. In the present study, we examined the effects of GlcN on chondrogenesis of human MSCs (hMSCs) and the phenotype of normal and osteoarthritic human articular chondrocytes, using an in vitro pellet culture model maintained in a defined medium. METHODS: hMSCs and normal and osteoarthritic human chondrocytes grown as pellet cultures, stimulated or not with interleukin-1beta (IL-1beta), were treated with varying doses of GlcN. Expression of cartilage matrix genes and cartilage degrading enzymes was determined by semiquantitative and quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), and by histological staining of cartilage markers, as well as sulfated GAG (sGAG) analysis and Western blotting. RESULTS: Chondrocytes grown in the presence of serum for 11 days showed decreased expression of the cartilage matrix genes, collagen type II (collagen II) and aggrecan, as early as day 3, which was reversed with GlcN treatment by day 11. Both hMSCs and chondrocytes grown as pellet cultures in defined medium and treated with 100 microM GlcN exhibited enhanced expression of collagen II and aggrecan as well as increased content of sGAG, when compared to control untreated pellets. However, high doses of GlcN (10 20mM) were inhibitory. GlcN treatment partially blocked IL-1beta mediated downregulation of collagen II and aggrecan expression and inhibited expression of the matrix degrading enzyme, matrix metalloproteinase 13 (MMP-13), in both chondrocytes and hMSCs undergoing chondrogenesis. CONCLUSIONS: These observations suggest that GlcN treatment enhances hMSC chondrogenesis and maintains cartilage matrix gene expression in chondrocytes, which may account for some of the reported chondroprotective properties of GlcN on cartilage. PMID- 17337216 TI - Expression of KIT receptor tyrosine kinase protein in normal human skin: preliminary observations. AB - KIT proto-oncogene is a receptor tyrosine kinase critical for signal transduction in several cell types. An understanding of KIT distribution in normal skin may reveal new insights into its implication in cutaneous biology and its associated disease states. This study examines expression patterns of KIT protein in normal human skin. KIT protein expression was examined in 50 specimens of normal human skin using specific antibodies (CD117) and immunoperoxidase staining methods. KIT protein expression was seen in keratinocytes (stratum basale), melanocytes, mast cells, and in both sebaceous and sweat glands. In contrast, KIT protein expression was absent in stratum spinosum, stratum granulosum, stratum corneum, blood vessels and arrector pili muscle. Thus, the expression of KIT protein in normal human skin suggests its possible role in regulation of cutaneous development and function. PMID- 17337217 TI - Analysis of the monovalent ion fluxes in U937 cells under the balanced ion distribution: recognition of ion transporters responsible for changes in cell ion and water balance during apoptosis. AB - Unidirectional (22)Na, Li(+) and Rb(+) fluxes and net fluxes of Na(+) and K(+) were measured in U937 human leukemic cells before and after induction of apoptosis by staurosporine (1 microM, 4 h) to answer the question which ion transporter(s) are responsible for changes in cell ion and water balance at apoptosis. The original version of the mathematical model of cell ion and water balance was used for analysis of the unidirectional ion fluxes under the balanced distribution of major monovalent ions across the cell membrane. The values of all major components of the Na(+) and K(+) efflux and influx, i.e. fluxes via the Na(+),K(+)-ATPase pump, Na(+) channels, K(+) channels, Na/Na exchanger and Na-Cl symport were determined. It is concluded that apoptotic cell shrinkage and changes in Na(+) and K(+) fluxes typical of apoptosis in U937 cells induced by staurosporine are caused by a complex decrease in the pump activity, Na-Cl symport and integral Na(+) channel permeability. PMID- 17337218 TI - Selective inactivation of the ventral hippocampus attenuates cue-induced and cocaine-primed reinstatement of drug-seeking in rats. AB - Recent evidence suggests that the hippocampus may have a functional role in mediating relapse to cocaine-seeking behavior. Based on the importance of the ventral CA subfields in mediating reward, the present experiment determined the effects of temporary inactivation of the ventral hippocampus on reinstatement of cocaine-seeking in a rodent model of relapse. Male, Sprague-Dawley rats self administered i.v. cocaine (0.6 mg/kg/infusion) in the presence of discrete conditioned cues (tone+light) in daily 2-h sessions for ten days. Following seven days of extinction sessions in which neither cues nor drug were available, rats underwent four reinstatement tests in a counterbalanced, within-subjects design. Bilateral microinjections of GABA receptor agonists (baclofen/muscimol (B/M; 1.0 mM/0.1 mM) [corrected] into the ventral hippocampus significantly attenuated cue induced and cocaine-primed reinstatement compared with vehicle microinjections in the same rats. In contrast, injections just outside the ventral hippocampus did not block either form of reinstatement. Furthermore, inactivation failed to affect responding for food reinforcement, baseline extinction responding, or locomotor activity. These data indicate that the ventral hippocampus plays an important role in the relapse to cocaine-seeking behavior and may interact with key limbic structures previously implicated in cocaine addiction. PMID- 17337219 TI - Characterization of the SKN7 ortholog of Aspergillus fumigatus. AB - Reactive oxidant intermediates play a major role in the killing of Aspergillus fumigatus by phagocytes. In yeasts, SKN7 is a transcription factor contributing to the oxidative stress response. We investigated here the role of afSkn7p in the adaptation of A. fumigatus against oxidative stress. To analyze functionally the afSKN7 in A. fumigatus, we modified a quick PCR fusion methodology for targeted deletion in A. fumigatus. The afskn7Delta mutant was morphologically similar to the wild-type strain, but showed a growth inhibition phenotype associated with hydrogen peroxide and tert-butyl hydroperoxide. However, no significant virulence differences were observed between wild type, mutant and reconstituted strains in a murine model of pulmonary aspergillosis. This result indicated that an increased sensitivity of A. fumigatus to peroxides in vitro is not correlated with a modification of fungal virulence. PMID- 17337220 TI - Calculated signal-to-noise ratio of MRI detected with SQUIDs and Faraday detectors in fields from 10 microT to 1.5 T. AB - We examine the calculated signal-to-noise ratio (SNR) achievable with different MRI detection modalities in precession fields ranging from 10 microT to 1.5 T. In particular, we compare traditional Faraday detectors with both tuned and untuned detectors based on superconducting quantum interference devices (SQUIDs). We derive general expressions for the magnetic field noise due to the samples and the detectors, and then calculate the SNR achievable for a specific geometry with each modality with and without prepolarization. We show that each of the three modalities is superior in one of the three field ranges. SQUID-based detection is superior to conventional Faraday detection for MRI in precession fields below 250 mT for a 65 mm diameter surface coil placed a distance of 25 mm from the voxel of interest embedded in a cylinder of tissue 50 mm tall and of radius 50 mm. This crossover field, however, is sensitive to the geometry. PMID- 17337221 TI - Energetics in a solitary subterranean rodent, the silvery mole-rat, Heliophobius argenteocinereus, and allometry of RMR in African mole-rats (Bathyergidae). AB - Low resting metabolic rate (RMR) in subterranean rodents used to be considered as a physiological adaptation to cope with stresses of the belowground environment. In African mole-rats (Bathyergidae, Rodentia), RMR was reported to be independent of body mass. This deviation from a general mammalian pattern was considered a precondition for evolution of eusociality, occurring in some bathyergids. We measured metabolic rate and thermoregulation in the silvery mole-rat, Heliophobius argenteocinereus, the only bathyergid genus for which well supported, comparable data were still missing. Low RMR (154.04 mL O(2) h(-1), which is 82% of the value predicted for a rodent) corresponds to the value expected in a subterranean rodent. Broad range of the thermoneutral zone (25-33 degrees C) and only slightly higher conductance (17.3 mL O(2) h(-1) degrees C( 1), i.e. 112.5% of that predicted for subterranean mammals) indicate that H. argenteocinereus is adapted to lower burrow temperatures rather than to high temperatures. Low RMR in this solitary species, as in other subterranean rodents in general, is probably associated particularly with high energetic cost of foraging. Our results combined with data on other mole-rats show clearly that RMR within the Bathyergidae is mass-dependent. PMID- 17337222 TI - The heart as a working model to explore themes and strategies for anoxic survival in ectothermic vertebrates. AB - Most vertebrates die within minutes when deprived of molecular oxygen (anoxia), in part because of cardiac failure, which can be traced to an inadequate matching of cardiac ATP supply to ATP demand. Cardiac power output (PO; estimated from the product of cardiac output and central arterial pressure and an indirect measure of cardiac ATP demand) is directly related to cardiac ATP supply up to some maximal level during both normoxia (ATP supply estimated from myocardial O(2) consumption) and anoxia (ATP supply estimated from lactate production rates). Thus, steady state PO provides an excellent means to examine anoxia tolerance strategies among ectothermic vertebrates by indicating a matching of cardiac glycolytic ATP supply and demand. Here, we summarize in vitro measurements of PO data from rainbow trout, freshwater turtles and hagfishes to provide a reasonable benchmark PO of 0.7 mW g(-1) for maximum glycolytic potential of ectothermic hearts at 15 degrees C, which corresponds to a glycolytic ATP turnover rate of about 70 nmol ATP g(-1) s(-1). Using this benchmark to evaluate in vivo PO data for hagfishes, carps and turtles, we identify two cardiac survival strategies, which in conjunction with creative waste management techniques to reduce waste accumulation, allow for long-term cardiac survival during anoxia in these anoxia tolerant species. Hagfish and crucian carp exemplify a strategy of evolving such a low routine PO that routine cardiac ATP demand lies within the range of the maximum cardiac glycolytic potential. Common carp and freshwater turtles exemplify an active strategy of temporarily and substantially decreasing cardiac and whole body metabolism so that PO is below maximum cardiac glycolytic potential during chronic anoxia despite being quite close to this potential under normoxia. PMID- 17337223 TI - Identification of novel SALMFamide neuropeptides in the starfish Marthasterias glacialis. AB - The SALMFamides are a family of neuropeptides found in species belonging to the phylum Echinodermata and which act as muscle relaxants. The first two members of this family to be identified were both isolated from the starfishes Asterias rubens and Asterias forbesi and are known as S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide). However, little is known about the occurrence and characteristics of SALMFamide neuropeptides in other starfish species. Here we report the identification of four SALMFamide neuropeptides in the starfish Marthasterias glacialis: GFNSALMFamide (S1), SGPYSMTSGLTFamide (MagS2), AYHSALPFamide (MagS3), and AYQTGLPFamide (MagS4). Analysis of the effects of MagS2 and MagS3 on cardiac stomach preparations from Asterias rubens revealed that both peptides cause dose-dependent relaxation, consistent with previous studies using S1 and S2. The identification of four SALMFamide neuropeptides in Marthasterias glacialis provides new insights into the diversity and phylogenetic distribution of SALMFamide neuropeptides in the class Asteroidea of the phylum Echinodermata. In particular, the identification of MagS3 and MagS4, in addition to S1 and the S2-like peptide MagS2, has revealed a greater diversity of SALMFamide neuropeptides occurring in a starfish species than any previous studies. PMID- 17337224 TI - Chronic nasal infection caused by Klebsiella rhinoscleromatis or Klebsiella ozaenae: two forgotten infectious diseases. AB - OBJECTIVES: Klebsiella rhinoscleromatis and Klebsiella ozaenae are associated with chronic diseases of the upper airways: rhinoscleroma and ozena, respectively. These have become uncommon in developed countries. We report herein one case of each disease in patients living in Marseilles, France, and include a review of the literature. METHODS: Diagnosis was made by direct evidence of bacteria (specific cultures and autoimmunohistochemistry on nasal biopsy) and using an indirect method (serology). In addition, the literature review showed that the majority of publications were old, confirming the fact that these diseases have been long forgotten. RESULTS: The specific and original methods used have allowed us to confirm the pathogenic role of K. ozaenae in ozena and confirmed rhinoscleroma in a granulomatous lesion. In the literature, K. rhinoscleromatis is only associated with rhinoscleroma whereas K. ozaenae is also associated with clinical diseases other than chronic rhinitis. CONCLUSIONS: In cases of chronic rhinitis, ozena and rhinoscleroma should be kept in mind, even in developed countries, and systematically screened for, especially as there are specific diagnostic tools and effective treatments available. PMID- 17337225 TI - Imipenem-resistance in Klebsiella pneumoniae in Malaysia due to loss of OmpK36 outer membrane protein coupled with AmpC hyperproduction. PMID- 17337226 TI - Bloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon: a view of the past decade. AB - OBJECTIVES: Previous studies from Lebanon have shown Gram-negative organisms to be the predominant agents in febrile neutropenic patients. The objective of this study was to evaluate the most current epidemiological trends among patients with neutropenic fever. METHODS: This prospective observational cohort study, the largest to date in the country, was conducted at the American University of Beirut Medical Center between January 2001 and December 2003, with the objective of describing the characteristics of patients with neutropenic fever and to assess temporal trends. RESULTS: We included 177 episodes of neutropenic fever. The most common underlying malignancy was lymphoma (42.4%). Gastrointestinal and abdominal infections were predominant (31.6%) and 23.7% of cases represented fever of unknown origin. Gram-negative organisms were responsible for 78.8% (26/33) of bloodstream infections compared to 33.3% (11/33) with Gram-positive organisms. The in-hospital mortality rate in this study (12.1%) was considerably lower than in previous years. CONCLUSIONS: Gram-negative organisms are persistently predominant in our center. In a developing country like Lebanon with limited resources, lower mortality rates commensurate with worldwide reports were successfully achieved in this high-risk patient population. Protocols and guidelines should be adapted to the characteristics of individual institutions to ensure delivery of appropriate care to febrile neutropenic patients. PMID- 17337227 TI - Coexistence in unusual locations of hydatid cysts: thigh, breast and lung involvement. PMID- 17337228 TI - Anterior femoroacetabular impingement. AB - Anterior femoroacetabular impingement is a mechanical hip disorder defined as abnormal contact between the anterior acetabular rim and the proximal femur. The typical patient is a young man who practices a martial art that involves kicking. Mechanical groin pain is the main presenting symptom. Passive flexion and internal rotation of the hip replicates the pain. The range of internal rotation is often limited. Imaging studies show a non-spherical femoral head or overhang of the anterior acetabular rim. Computed arthrotomography or magnetic resonance arthrography visualize focal damage to the anterosuperior labrum and sometimes to the acetabular cartilage. Discontinuing the activity associated with the harmful hip movement is the main treatment. However, arthroplasty and removal of damaged labral tissue may be required. Surgical outcomes correlate negatively with the severity of the cartilage lesions. PMID- 17337229 TI - Cat scratch disease during etanercept therapy. AB - Lymphadenopathy in a patient taking TNFalpha antagonist therapy may indicate lymph node tuberculosis or a hematological malignancy. Although histological evidence of granuloma suggests tuberculosis, many other infections responsible for granulomatous reactions have been reported in patients on TNFalpha antagonist therapy. We report a case of granulomatous lymphadenopathy due to Bartonella henselae in a patient taking etanercept to treat ankylosing spondylitis. PMID- 17337230 TI - Pseudohyperphosphatemia in multiple myeloma. PMID- 17337231 TI - [Interest in agents for adhesion prevention after gynecologic surgery]. AB - Adhesion barriers are intraperitoneal agents, solid or fluid, developed in order to prevent postoperative adhesions. In this article, we evaluate the efficiency of these new barrier agents for adhesion prevention in gynaecologic surgery, undertaking a review of controlled clinical trials published. Several human clinical trials demonstrated the safety and efficiency of both Interceed and Seprafilm. As far as other barrier agents are concerned, data are still insufficient to recommend them for clinical use. There is a need for other randomised controlled trials in order to evaluate functional efficiency of anti adhesion agents. PMID- 17337232 TI - Nitric oxide: ocular blood flow, glaucoma, and diabetic retinopathy. AB - Nitric oxide (NO) is widely recognized to be quite an important intercellular messenger in the cardiovascular and nervous systems or immunological reactions, including that in the eye. This molecule formed by constitutive NO synthase (NOS), endothelial (eNOS) and neuronal (nNOS), contributes to physiologically regulate ocular hemodynamics and cell viability and protects vascular endothelial cells and nerve cells or fibers against pathogenic factors associated with glaucoma, ischemia, and diabetes mellitus. Ocular blood flow is regulated by NO derived from the endothelium and efferent nitrergic neurons. Endothelial dysfunction impairs ocular hemodynamics by reducing the bioavailability of NO and increasing the production of reactive oxygen species (ROS). On the other hand, NO formed by inducible NOS (iNOS) expressed under influences of inflammatory mediators evokes neurodegeneration and cell apoptosis, leading to serious ocular diseases. NO over-produced by nNOS in the retina stimulated by excitotoxic amino acids or exposed to ischemia also mediates retinal injury. Because of these dichotomous roles of NO, which has both beneficial and pathogenic actions, one may face difficulties in constructing therapeutic strategies with NO supplementation or NOS inhibition. Up-to-date information concerning physiological roles of NO produced by the different NOS isoforms in the eye and interactions between NO and glaucoma, retinal ischemia, or diabetic retinopathy would help clinicians to select a valid pharmacological therapy that would be appropriate for a specific ocular disease. PMID- 17337233 TI - Use of a novel method to find substrates of protein kinase C delta identifies M2 pyruvate kinase. AB - Protein kinase C (PKC) family members have been implicated in numerous cellular processes. However, identifying the substrates of each PKC isozyme remains a challenge. Here, we describe a method using two-dimensional (2D) isoelectric focusing gel electrophoresis to identify substrates of delta PKC (deltaPKC) in MCF-7 breast carcinoma cells. We show that M2 pyruvate kinase is a substrate of deltaPKC, and further characterize the interaction between M2 pyruvate kinase and deltaPKC in MCF-7 cells by immunoprecipitation. deltaPKC activation in vitro or in cells did not appear to alter the enzyme activity or polymerization of M2 pyruvate kinase. PMID- 17337234 TI - Cloning and functional characterization of 5'-upstream region of metallothionein I gene from crucian carp (Carassius cuvieri). AB - Metallothioneins are low molecular weight, cysteine-rich, metal-binding proteins, which can be induced by heavy metal ions, cytokines, stress, and hormones. To investigate the roles of the main cis-acting elements involved in the inducible expression of metallothionein gene in fish, the 5'-upstream region of crucian carp (Carassius cuvieri) metallothionein-I gene had been cloned and analyzed after our previous work on metallothionein-II. In its upstream region, several putative cis-acting elements, including nine metal regulatory elements (MREs), one antioxidant response element, one E-box, and three interleukin-6 responsive elements, etc. were found. The nine metal regulatory elements are confined in less than 1000 bp from ATG start codon and organized into two clusters with different roles to the induction of the metallothionein-I expression. Deletion mutant assays demonstrated that both the distal and proximal clusters of metal regulatory elements contributed to the basal expression of the metallothionein-I, but only the proximal cluster was the chief contributor to the metal fold induction. In transient luciferase reporter assays, Zn2+ and Cd2+ served as much stronger inducers than Cu2+ to the metallothionein-I expression. H2O2 also could activate the metallothionein-I promoter about two-fold, which was mediated by the antioxidant response element (TGACAACGC, -437/-445). In conclusion, our studies demonstrate the roles of metal regulatory element and antioxidant response element in the induction of crucian carp metallothionein-I gene, and provide the regulatory mechanism for the use of fish metallothionein as a biomarker for monitoring of metal contamination in waters. PMID- 17337235 TI - Cross-talk between apoptosis and cytokines in the regulation of parasitic infection. AB - Parasitic diseases have worldwide medical and economical impact. Host T lymphocytes and the cytokines they produce determine the outcome of parasitic infections. Programmed cell death by apoptosis is induced in the course of parasitic infections, and affects cytokine production by removing activated effector T and B cells. In addition, engulfment of apoptotic cells promotes the secretion of cytokines that regulate intracellular replication of protozoan parasites. In this review, we discuss how the cross-talk between apoptosis and cytokines regulates parasitic infection. PMID- 17337236 TI - Celebrating a decade of TiCS. PMID- 17337237 TI - Contrasting roles for cingulate and orbitofrontal cortex in decisions and social behaviour. AB - There is general acknowledgement that both the anterior cingulate and orbitofrontal cortex are implicated in reinforcement-guided decision making, and emotion and social behaviour. Despite the interest that these areas generate in both the cognitive neuroscience laboratory and the psychiatric clinic, ideas about the distinctive contributions made by each have only recently begun to emerge. This reflects an increasing understanding of the component processes that underlie reinforcement-guided decision making, such as the representation of reinforcement expectations, the exploration, updating and representation of action values, and the appreciation that choices are guided not just by the prospect of reward but also by the costs that action entails. Evidence is emerging to suggest that the anterior cingulate and orbitofrontal cortex make distinct contributions to each of these aspects of decision making. PMID- 17337238 TI - The Spectroscopy: a modern technology in the characterization of novel macrocyclic ligand and its homo-bi-nuclear cobalt (II) complexes. AB - A novel hexadentate nitrogen-sulphur donor [N(4)S(2)] macrocyclic ligand, i.e. 3,13-dithio-6,10,16,20-tetraoxo-8,18-dithia-1,2,4,5,11,12,14,15 octaazacyclocosane (L), has been synthesized. Cobalt (II) complexes of this ligand have been prepared and subjected to elemental analyses, molar conductance measurements, magnetic moment susceptibility measurements, mass, (1)H NMR (Ligand), IR, electronic, and EPR spectral studies. On the basis of molar conductance, complexes may be formulated as [Co(2)(L)X(2)]X(2) [where X=Cl(-), Br(-), NO(3)(-) and NCS(-)] due to their 1:2 electrolytic nature in dimethylformamide (DMF). All the complexes are of the high spin type and are four coordinated. On the basis of IR, electronic and EPR spectral studies tetrahedral geometry has been assigned to all the complexes. The antimicrobial activities of the ligand and its complexes, as growth inhibiting agents, have been screened in vitro against several species of bacteria and plant pathogenic fungi. PMID- 17337239 TI - A sequential injection method for the fluorimetric determination of aluminum in drinking water using 8-hydroxy-7-(4-sulfo-1-naphthylazo)-5-quinoline sulfonic acid. AB - A robust and simple sequential injection (SI) method for the assay of aluminum ions in drinking water is described. The method is based on the complex formation between aluminum and 8-hydroxy-7-(4-sulfo-1-naphthylazo)-5-quinoline sulfonic acid (HSNQ). The fluorescence of the complex is monitored at an emission wavelength of 492 nm with excitation at 357 nm. The HSNQ concentration, aspirated reagent and sample volumes were optimized simultaneously using 3(3) full factorial design. The optimum operating conditions are aspirated sample and reagent volumes of 90 and 70 microL, respectively, and HSNQ concentration of 20 microM. With these conditions linear calibration curves were obtained from 100 to 800 ppb. The detection limit was 4 ppb. The maximum relative standard deviation of the method was 1.43% (n=5). The method was successfully applied for the determination of aluminum in drinking water samples. PMID- 17337240 TI - Investigation of the effect of tanshinone IIA on nitric oxide production in human vascular endothelial cells by fluorescence imaging. AB - Nitric oxide (NO) has been proved to be a potent vasodilator that played an important role in regulating vascular tones. Tanshinone, one of the active components of Radix Salvia miltiorrhiza, was used widely in clinics in China for treating cardiovascular diseases. The objective of this study was to sensitively and specifically investigate the effects of tanshinone IIA, one important pharmacological constituent of tanshinone, on the release of NO from human vascular endothelial cells (HVECs) by fluorescence imaging with an excellent fluorescent probe 1,3,5,7-tetramethyl-2,6-dicarbethoxy-8-(3',4'-diaminophenyl) difluoroboradiaza-s-indacence (TMDCDABODIPY). After cells were incubated with tanshinone IIA, TMDCDABODIPY was employed to label NO. Following the tagging, real-time imaging of NO release from the cells was performed with inverted fluorescence microscope. The results of the experiments showed that tanshinone IIA could induce NO production significantly enhanced in HVECs. The activation of NO by tanshinone IIA may be employed therapeutically in modulating NO production in HVECs. PMID- 17337241 TI - Parvovirus B19-brain interactions: infection, autoimmunity, or both? PMID- 17337242 TI - The German Human Biomonitoring Commission. AB - In Germany, the Human Biomonitoring Commission of the German Federal Environment Agency was established in 1992 to develop scientifically based criteria for the application of human biomonitoring (HBM). The goal is to clarify fundamental and practical issues related to HBM. Following the assessment of pollutants in body fluids, the commission derives two different kinds of guideline values: reference values and HBM values (HBM I and HBM II values). This article gives a review of the current reference values, HBM values, and the work of the German Human Biomonitoring Commission. PMID- 17337243 TI - An audit of clinically relevant abnormal laboratory parameters investigating athletes with persistent symptoms of fatigue. AB - The aim of this audit was to assess the yield of a selection of laboratory tests as part of the clinical assessment of the fatigued athlete. Clinical charts and blood test results of fifty consecutive athletes who presented with the primary complaint of fatigue were retrospectively reviewed. Blood tests results reviewed were: haematology (haemoglobin, red cell count, mean cell volume, mean cell haemoglobin content, platelets, white cell count, differential white cell count); erythrocyte sedimentation rate; serum biochemistry (urea, creatinine, electrolytes, urate, glucose, liver function tests, albumin, globulin); blood iron status (serum iron, total iron binding capacity, percent transferring saturation, and ferritin concentration); thyroid stimulating hormone; and immune measures (Epstein-Barr virus serology, cytomegalovirus serology). We identified only 3 abnormal results that contributed to the diagnosis of medical disease as a cause for fatigue. Laboratory testing identified 2 fatigued female athletes with serum ferritin concentration between 15 microg L(-1) and 20 microg L(-1) plus two of the other criteria of iron concentration (serum iron <10 micromol L(-1), iron binding capacity > 68 micromol L(-1), or transferrin saturation <15%). We concluded that the yield from a selection of blood tests investigating fatigued athletes was low. Future study is needed to further define the role of laboratory testing and to study whether low iron stores in the absence of anaemia is related to symptoms in fatigued athletes. PMID- 17337244 TI - Pulmonary alveolar proteinosis in extremis: the case for aggressive whole lung lavage with extracorporeal membrane oxygenation support. AB - Pulmonary alveolar proteinosis (PAP) is a rare disorder in which lipoproteinaceous material is deposited in the alveoli, compromising gaseous exchange. We report the case of a 29-year-old female patient presenting with the most extreme case of PAP yet reported. She successfully managed by aggressive bilateral whole lung lavage (WLL) in a single sitting using extracorporeal membrane oxygenation (ECMO) support. Despite critical hypercarbia and ventilator dependence for 12 days before lavage, the patient experienced rapid recovery of pulmonary function after WLL and ECMO could be discontinued on-table. Aggressive WLL with ECMO support can be safe and effective even in the most severe cases of PAP. PMID- 17337245 TI - Abstracts of the 38th Annual Conference of the International Society of Paediatric Oncology. September 2006. Geneva, Switzerland. PMID- 17337246 TI - Resolvins and protectins in the termination program of acute inflammation. AB - The physiological resolution of a well-orchestrated inflammatory response is essential to maintain homeostasis. Therefore, gaining a comprehensive understanding in molecular terms of the events that direct the termination of acute inflammation is imperative. Recently, new families of local-acting mediators were discovered that are biosynthesized from the essential fatty acids eicosapentaenoic acid and docosahexaenoic acid. These new chemical mediators are endogenously generated in inflammatory exudates collected during the resolution phase, and were termed resolvins and protectins because specific members of these families control the magnitude and duration of inflammation in animals. In addition, recent results indicate novel actions of resolvins and protectins in removing chemokines ferried from the tissue by apoptotic neutrophils and T cells during resolution. Here, we review recent advances on the biosynthesis and actions of these novel anti-inflammatory and proresolving mediators. PMID- 17337247 TI - Vitamin D receptor gene polymorphisms and susceptibility M. tuberculosis in native Paraguayans. AB - Tuberculosis (TB) is a significant health problem for most of the world's populations, and prevalence among indigenous groups is typically higher than among their nonindigenous neighbors. Native South Americans experience high rates of TB, but while research in several other world populations indicates that susceptibility is multifactorial, polygenic, and population-specific, little work has been undertaken to investigate factors involved in Native American susceptibility. We conducted a family-based association study to examine immunologically relevant polymorphisms of a candidate gene, the vitamin D receptor, in conjunction with three measures of TB status in two Native Paraguayan populations, the Ache and the Ava. This is the first large-scale genetic analysis of Native South Americans to examine susceptibility to both infection and disease following exposure to M. tuberculosis. These two types of susceptibility reflect differences in innate and acquired immunity that have proven difficult to elucidate in other populations. Our results indicate that among the Ache, the FokI F allele protects individuals from infection, while the TaqI t allele protects against active disease but not infection. In particular, FF homozygotes are 17 times more likely to test positive for exposure to TB, but no more likely to have ever been diagnosed with active TB. TT individuals are 42 times less likely to mount a delayed-type hypersensitivity response, and the T allele was significantly more likely to have been transmitted to offspring who have been diagnosed with active TB. This ongoing research is of vital importance to indigenous groups of the Americas, because if there is a population-specific component to TB susceptibility, it will likely prove most effective to incorporate this into future treatment and prevention strategies. PMID- 17337248 TI - Mortality in epilepsy. AB - All studies report an increased mortality risk for people with epilepsy compared with the general population. Population-based studies have demonstrated that the increased mortality is often related to the cause of the epilepsy. Common etiologies include neoplasia, cerebrovascular disease, and pneumonia. Deaths in selected cohorts, such as sudden unexpected death in epilepsy (SUDEP), status epilepticus (SE), suicides, and accidents are more frequently epilepsy-related. SUDEP is a particular cause for concern in younger people, and whether and when SUDEP should be discussed with patients with epilepsy remain problematic issues. Risk factors for SUDEP include generalized tonic-clonic seizures, increased seizure frequency, concomitant learning disability, and antiepileptic drug polypharmacy. The overall incidence of SE may be increasing, although case fatality rates remain constant. Mortality is frequently secondary to acute symptomatic disorders. Poor compliance with treatment in patients with epilepsy accounts for a small proportion of deaths from SE. The incidence of suicide is increased, particularly for individuals with epilepsy and comorbid psychiatric conditions. Late mortality figures in patients undergoing epilepsy surgery vary and are likely to reflect differences in case selection. Future studies of mortality should be prospective and follow agreed guidelines to better quantify risk and causation in individual populations. PMID- 17337249 TI - Topiramate effects on the EEG and alertness in healthy volunteers: a different profile of antiepileptic drug neurotoxicity. AB - OBJECTIVE: Previous quantitative EEG (QEEG) studies of carbamazepine (CBZ), oxcarbazepine (OXC), and phenytoin (PHT) revealed a pattern of EEG slowing and an increase in drowsiness on the awake maintenance task (AMT). EEG slowing has been shown to correlate with negative effects on cognitive tests. Topiramate (TPM) is a novel AED with relatively large negative effects on cognitive function. We tested the hypothesis that TPM would induce significant slowing of EEG background rhythms and an increase in AMT drowsiness. METHODS: Forty healthy volunteers were randomized to TPM, gabapentin (GBP), or placebo. Doses were escalated as tolerated to a maximum of 400mg/day for TPM or 3600 mg/day for GBP, over a 10 week period, followed by a minimum 2-week plateau period. Volunteers underwent an EEG, cognitive tests, and the AMT prior to starting an AED and again 12 weeks later. The EEG was captured using a structured recording protocol and quantified using the fast Fourier transform. Four target measures were derived from the averaged occipital electrodes (peak frequency of the dominant posterior rhythm, median frequency, percentage theta, and percentage delta). Test-retest changes for all measures were scored against similar test-retest distributions previously obtained from untreated healthy volunteers. RESULTS: TPM produced no significant change in any of the four target EEG measures or on the AMT, even though several target cognitive tests revealed moderate or greater negative effects. There were also no significant changes in the placebo group. GBP slowed the peak and median frequency EEG measures and increased the percentage of theta and delta activity. Neither TPM, GBP, nor placebo caused a significant increase in drowsiness on the AMT. CONCLUSIONS: TPM has a unique neurotoxicity profile. It has no effect on EEG background measures or on the AMT, but induces moderate to large negative changes in many cognitive test scores. This profile differs from those of CBZ, OXC, PHT, and GBP. PMID- 17337250 TI - Potentiation of nociceptive responses to low pH injections in humans by prostaglandin E2. AB - Inflammation and trauma lead to tissue acidification and release of inflammatory mediators, including prostaglandin E2 (PGE2). Protons can evoke pain through acid sensing ion channels (ASICs) and TRPV1 receptors. In this study, we examined whether PGE2 can potentiate proton-induced nociception in humans on injection into skin and muscle. Psychophysical and vascular responses to microinjections of protons (pH 6.0 and 6.5), PGE2 (10-6 and 10-7 M) and their combinations into forearm skin (30 microL) or anterior tibial muscle (50 microL) were assessed in 16 male subjects. Pain intensity, axon reflex erythema, and heat pain thresholds were recorded after skin challenge; pain intensity and thresholds for pressure evoked pain were recorded after intramuscular injections. Intradermal or intramuscular injections of PGE2 induced very low levels of pain similar to saline. Administration of low pH caused moderate pain within 5 seconds that declined rapidly over 15 to 20 seconds. In comparison, coinjection of low pH with PGE2 led to a biphasic profile of the pain response. Combined pH + PGE2 stimulation provoked significantly increased pain in the second phase after injections (20 to 100 seconds) both in skin and muscle, whereas the initial injection pain was not enhanced. Heat pain thresholds were reduced after PGE2 and combined pH + PGE2, whereas flare responses were rather attenuated on coadministration of low pH with PGE2. Intriguingly, when compared with skin, muscle pain was significantly lower in the initial phase (0 to 15 seconds) but significantly higher in the second phase (20 to 100 seconds after injection). PERSPECTIVE: PGE2 can potentiate nociceptor activation by protons in human skin and muscle, indicated by increased sustained pain ratings. This can be best explained by TRPV1 sensitization in the presence of PGE2, a mechanism potentially relevant for inflammatory and injury-induced pain. PMID- 17337251 TI - Comorbidity of obesity and pain in a general population: results from the Southern Pain Prevalence Study. AB - This cross-sectional study examines the relation between obesity and self reported pain (moderate or severe pain occurring at least monthly) in a general population sample of adults in the southeastern United States (N = 3637). Results of the study suggest that obese adults (body mass index [BMI] >30) are more likely to experience pain than their normal-weight and underweight counterparts. Respondents classified as class I obese (BMI of 30 to 34.9) were 1.762 times as likely as the underweight and normal weight participants to report severe pain. Class II obese respondents (BMI of 35 to 39.9) were 1.888 times as likely to experience severe pain. Those respondents categorized as class III obese were most likely to report severe pain--2.297 times as likely as the underweight and normal-weight respondents. Analyses demonstrated a similar trend for respondents reporting moderate to severe pain. Adults who are obese are also more likely to report experiencing pain in multiple locations. This study complements clinical research that links pain and obesity and extends it into a general population. Because this is a cross-sectional study, further research is needed to discern causal explanations for the relation between self-reported pain and obesity. PERSPECTIVE: This article provides a population-level depiction of the positive relation between obesity and self-reported pain, which complements clinical research on the topic. It may prompt future research to shape interventions and treatment for both pain and obesity. PMID- 17337252 TI - Molecular characterization and tissue distribution of aryl hydrocarbon receptor nuclear translocator isoforms, ARNT1 and ARNT2, and identification of novel splice variants in common cormorant (Phalacrocorax carbo). AB - High levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons (PHAHs) are accumulated in fish-eating birds including common cormorant (Phalacrocorax carbo). Most of the biochemical and toxic effects of TCDD are mediated by a basic helix-loop-helix and a conserved region among Per, ARNT, and Sim (bHLH/PAS) proteins, aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT). To study the molecular mechanism of TCDD toxicity in common cormorant as an avian model species, characterization of the AHR/ARNT signaling pathway in this species is necessary. The present study focuses on molecular characterization of ARNT from common cormorant (ccARNT). The cDNA of the ccARNT isoform, ccARNT1 obtained by the screening of hepatic cDNA library contains a 2424-bp open reading frame that encodes 807 amino acids, exhibiting high identities (92%) with chicken ARNT. This isoform contains a unique 22 amino acid residue in 3' end of PAS A domain as is also recognized in chicken ARNT. The ccARNT2 cDNA isolated from brain tissue has a 2151-bp open reading frame. The deduced amino acid sequence of ccARNT2 protein (716 aa) shows a conservation of bHLH and PAS motif in its N-terminal region with high similarities (96% and 78%, respectively) to that of ccARNT1. Using quantitative RT-PCR methods, the tissue distribution profiles of ccARNT1 and ccARNT2 were unveiled. Both ccARNT1 and ccARNT2 mRNAs were ubiquitously expressed in all examined tissues including liver. The expression profile of ccARNT1 was comparable with that of rodent ARNT1, but ccARNT2 was not with rodent ARNT2, implying different roles of ARNT2 between the two species. There was a significant positive correlation between ARNT1 and ARNT2 mRNA expression levels in the liver of wild cormorant population, indicating that their expressions may be enforced by similar transcriptional regulation mechanism. Novel variants of ccARNT1 and ccARNT2 isoforms that were supposed to arise from their splicing process were also identified and their hepatic expression profiles were determined. These results indicate that ccARNT1, ccARNT2 and their splice variants may more intricately regulate the AHR/ARNT signaling pathway and consequently may be responsible for the species diversity of toxic effects and susceptibility to PHAHs. PMID- 17337253 TI - Renal function in the freshwater rainbow trout after dietary cadmium acclimation and waterborne cadmium challenge. AB - Renal function was examined in adult rainbow trout (Oncorhynchus mykiss) after chronic exposure to a sublethal level of dietary Cd (500 mg/kg diet) for 52 d and during a subsequent challenge to waterborne Cd (10 microg/L) for 72 h. Dietary Cd had no major effects on UFR (urine flow rate) and GFR (glomerular filtration rate) but caused increased renal excretion of glucose, protein, and major ions (Mg(2+), Zn(2+), K(+), Na(+), Cl(-) but Ca(2+)). However, dietary Cd did not affect any plasma ions except Na(+) which was significantly elevated in the Cd acclimated trout. Plasma glucose and ammonia levels fell by 25% and 36% respectively, but neither plasma nor urine urea was affected in Cd-acclimated fish. Dietary Cd exposure resulted in a remarkable increase of Cd load in the plasma (48-fold, approximately 22 ng/mL) and urine (60-fold, 8.9 ng/mL), but Cd excretion via the kidney was negligible on a mass-balance basis. Clearance ratio analysis indicates that all ions, Cd, and metabolites were reabsorbed strongly (58-100%) in both naive and dietary Cd exposed fish, except ammonia which was secreted in both groups. Mg(2+), Na(+), Cl(-) and K(+) reabsorption decreased significantly (3-15%) in the Cd-exposed fish relative to the control. Following waterborne Cd challenge, GFR and UFR were affected transiently, and only Mg(2+) and protein excretion remained elevated with no recovery with time in Cd acclimated trout. Urinary Ca(2+) and Zn(2+) excretion rates dropped with an indication of renal compensation towards plasma declines of both ions. Cadmium challenge did not cause any notable effects on urinary excretion rates of metabolites. However, a significant decrease in Mg(2+) reabsorption but an increase in total ammonia secretion was observed in the Cd-acclimated fish. The study suggests that dietary Cd acclimation involves physiological costs in terms of renal dysfunction and elevated urinary losses. PMID- 17337254 TI - The PPARgamma ligand, rosiglitazone, reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice. AB - Oxidative stress plays an important role in diabetic vascular dysfunction. The sources and regulation of reactive oxygen species production in diabetic vasculature continue to be defined. Because peroxisome proliferator-activated receptor gamma (PPARgamma) ligands reduced superoxide anion (O(2)(-.)) generation in vascular endothelial cells in vitro by reducing NADPH oxidase and increasing Cu/Zn superoxide dismutase (SOD) expression, the current study examined the effect of PPARgamma ligands on vascular NADPH oxidase and O(2)(-.) generation in vivo. Lean control (db(+)/db(-)) and obese, diabetic, leptin receptor-deficient (db(-)/db(-)) mice were treated with either vehicle or rosiglitazone (3 mg/kg/day) by gavage for 7-days. Compared to controls, db(-)/db(-) mice weighed more and had metabolic derangements that were not corrected by treatment with rosiglitazone for 1-week. Aortic O(2)(-.) generation and mRNA levels of the NADPH oxidase subunits, Nox-1, Nox-2, and Nox-4 as well as Nox-4 protein expression were elevated in db(-)/db(-) compared to db(+)/db(-) mice, whereas aortic Cu/Zn SOD protein and PPARgamma mRNA levels were reduced in db(-)/db(-) mice. Treatment with rosiglitazone for 1-week significantly reduced aortic O(2)(-.) production and the expression of Nox-1, 2, and 4 but failed to increase Cu/Zn SOD or PPARgamma in aortic tissue from db(-)/db(-) mice. These data demonstrate that the vascular expression of Nox-1, 2, and 4 subunits of NADPH oxidase is increased in db(-)/db(-) mice and that short-term treatment with the PPARgamma agonist, rosiglitazone, has the potential to rapidly suppress vascular NADPH oxidase expression and O(2)(-.) production through mechanisms that do not appear to depend on correction of diabetic metabolic derangements. PMID- 17337255 TI - Detection of Chagas infections using Trypanosoma evansi crude antigen demonstrates high cross-reactions with Trypanosoma cruzi. AB - Antigenic similarities between salivarian trypanosomes are known for a long time, but similarities between salivarian and stercorarian trypanosomes have been very little investigated. Phylogenetically, these genus and species appear to be far. However, in a preliminary work we had shown strong reactions of chagasic human sera using T. evansi antigens in Western-blotting and ELISA. In the current work an ELISA test using T. evansi crude antigens was probed with one hundred and two sera of chagasic Bolivian patients previously diagnosed which presented different pathologies. The sensitivity of the ELISA T. evansi was 92.6% similar to that of ELISA T. cruzi. The specificity evaluated using 20 sera of patients infected by Leishmania sp. reaches a comparable value of that obtained with the T. cruzi immunofluorescent assay. Finally, the sensitivity and the specificity of the ELISA T. evansi were not really different from conventional serology of Chagas. In spite of their taxonomic position in various sections and their old divergence, these observations prove a strong antigenic community between T. cruzi and T. evansi. Consequently, the common antigens which remain to be characterized, could be an alternative source of antigen for the detection of antibodies against T. cruzi. Given that T. evansi seems to have strong antigenic communities with the majority of the pathogenic current trypanosomoses of mammals, it is very attractive to identify and characterize these highly conserved antigens which could be suitable targets to develop tools for diagnosis, prophylaxy and chemotherapy against several human and animal trypanosomoses. PMID- 17337256 TI - Effects of T-tubules on dielectric spectra of skeletal muscle simulated by boundary element method with two-dimensional models. AB - In order to investigate the origin of large intensity the alpha-relaxation in skeletal muscles observed in dielectric measurements with extracellular electrode methods, effects of the interfacial polarization in the T-tubules on dielectric spectra were evaluated with the boundary-element method using two-dimensional models in which the structure of the T-tubules were represented explicitly. Each model consisted of a circular inclusion surrounded by a thin shell corresponding to the sarcolemma. The T-tubules were represented by simplified two types of invagination of the shell: straight invagination along the radial directions, and branched one. Each of the models was subjected to two kinds of calculations relevant to experiments with the extracellular and the intracellular electrode methods. Electrical interactions between the cells were omitted in the calculations. Both calculations showed that the dielectric spectra of the models contained two relaxation terms. The low-frequency relaxation term assigned to the alpha-relaxation depended on the structure of the T-tubules. Values of the relaxation frequency of the alpha-relaxation obtained from the two types of calculations agreed with each other. At the low-frequency limit, the permittivity obtained from the extracellular-electrode-type calculations varied in proportion to the capacitance obtained from the intracellular-electrode-type ones. These results were consistent with conventional lumped and distributed circuit models for the T-tubules. This confirms that the interfacial polarization in the T tubules in a single muscle cell is not sufficient to explain the experimental results in which the intensity of the alpha-relaxation in the extracellular electrode-type experiments exceeded the intensity expected from the results of the intracellular-electrode-type experiments. The high-frequency relaxation term that was assigned to the beta-relaxation was also affected by the T-tubule structure in the calculations relevant to the extracellular-electrode-type experiments. PMID- 17337259 TI - Adult to adult living-related liver transplant: report on an initial experience in Italy. AB - INTRODUCTION: Living-related liver transplantation has become the treatment of choice for many liver diseases. We present our initial analysis of 53 cases of adult to adult living-related liver transplantation performed in a single institute in Italy. MATERIALS AND METHODS: From January 2002 to September 2006, we performed 53 adult to adult living-related liver transplantations. The donors (age 18-53) all had genetic or emotional relationships; they were all ABO identical or compatible. Recipients (ages 18-68) suffered from cirrhosis secondary to viral etiology (18), hepatocellular carcinoma with viral cirrhosis (24), cystic fibrosis (2), primary biliary cirrhosis (2), hepatocellular carcinoma with non-viral cirrhosis (2), alcoholic cirrhosis (1), ornithine transcarbamylase deficiency (OTC), (1) criptogenic cryptogenic cirrhosis, (1) primary sclerosing cholangitis, (1) biliary atresia and metastatic carcinoid (1). Donor liver resection resulted in 51 right hepatectomies and two left hepatectomies. Graft body weight ratio was always above 0.8%; graft implantation was performed with the piggy back technique and, in 43 cases, with the use of veno-venous bypass. RESULTS: There was neither donor mortality nor need of blood transfusion. Actuarial recipient survival rate at 3 years was 82.66% and graft survival rate was 75.34%. Six patients underwent retransplantation: in four cases due to hepatic artery thrombosis, and in two, due to graft dysfunction. Three patients had one episode each of acute cellular rejection. CONCLUSION: Adult to adult living-related liver transplantation represents a resource to be used in confronting organ shortage, and is a valuable option for decreasing mortality and drop out from the waiting list. PMID- 17337260 TI - Congenital cytomegalovirus infections. AB - Congenital cytomegalovirus (CMV) infection is one of the most common viral causes of congenital infections in high resource countries and a leading cause of hearing loss as well as an important contributor to neurodevelopmental disabilities in children. During early pregnancy, CMV has a teratogenic potential and may cause malformations such as migrational disturbances in the brain, which can be visualised using neuroimaging methods such as magnetic resonance imaging (MRI) in such children. As a consequence of variation in epidemiology and seropositivity in fertile women, the prevalence of congenital CMV in their offspring varies in different countries between 0.15-2.0%. Some 10-20% of all children with congenital CMV infections exhibit signs of neurological damage when followed up. This is the case in children both with and without symptoms of infection at birth. Until vaccines and non-toxic antiviral agents are available, hygienic measures are important as prophylaxis. Treatment with antiviral agents may have a place in children with central nervous system involvement during the neonatal period. PMID- 17337257 TI - A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification. AB - Base excision repair (BER) proteins act upon a significantly broad spectrum of DNA lesions that result from endogenous and exogenous sources. Multiple sub pathways of BER (short-path or long-patch) and newly designated DNA repair pathways (e.g., SSBR and NIR) that utilize BER proteins complicate any comprehensive understanding of BER and its role in genome maintenance, chemotherapeutic response, neuro-degeneration, cancer or aging. Herein, we propose a unified model of BER, comprised of three functional processes: Lesion Recognition/Strand Scission, Gap Tailoring and DNA Synthesis/Ligation, each represented by one or more multi-protein complexes and coordinated via the XRCC1/DNA Ligase III and PARP1 scaffold proteins. BER therefore may be represented by a series of repair complexes that assemble at the site of the DNA lesion and mediates repair in a coordinated fashion involving protein-protein interactions that dictate subsequent steps or sub-pathway choice. Complex formation is influenced by post-translational protein modifications that arise from the cellular state or the DNA damage response, providing an increase in specificity and efficiency to the BER pathway. In this review, we have summarized the reported BER protein-protein interactions and protein post-translational modifications and discuss the impact on DNA repair capacity and complex formation. PMID- 17337261 TI - Left-ventricular non-compaction in a patient with monosomy 1p36. AB - We report on a new-born girl with left ventricular non-compaction (LVNC), dysmorphism and epilepsy. Array-CGH at 1 Mb resolution revealed a deletion of the terminal 4.6 to 5.9 Mb of the short arm of chromosome 1. Cardiac abnormalities such as dilated cardiomyopathy and structural cardiac defects are common findings in patients with monosomy 1p36. This is however the first report describing LVNC in association with the 1p36 deletion syndrome, broadening the spectrum of cardiac anomalies found in association with this syndrome. PMID- 17337263 TI - The bone mineralization density distribution as a fingerprint of the mineralization process. AB - The inhomogeneous mineral content and its topographical distribution on a microscopic scale are major determinants of the mechanical quality of trabecular bone. The kinetics of bone tissue deposition and resorption together with the kinetics of the mineralization process determine the distribution of mineral in the tissue. The heterogeneity of the mineral content is described by the well established bone mineralization density distribution (BMDD), which is experimentally accessible, e.g., using quantitative electron backscattering imaging (qBEI). In the present work, we demonstrate that the shape of the BMDD histogram of trabecular bone reflects directly the mineralization kinetics. Based on the experimental BMDD data of trabecular bone from healthy human adults and using a mathematical model for the remodeling and the mineralization process, the following main results were obtained. The peaked BMDD reflects necessarily a two phase mineralization process with a fast primary phase and a slow secondary phase where the corresponding time constants differ three orders of magnitude. The obtained mineralization law, which describes the increase in the mineral content in a bone packet as a function of time, provides information not only about the initial mineralization surge, but also about the slow increase afterwards on the time scale of years. In addition to the mineralization kinetics the turnover rate of the remodeling process has a strong influence on the peak position and the shape of the BMDD. The described theoretical framework opens new possibilities for an analysis of experimentally measured BMDDs with respect to changes caused by diseases or treatments. It allows addressing whether changes in the BMDD have to be attributed to a variation in the turnover rate which consequently affects the density distribution or to a primary disorder in the mineralization process most likely reflecting alterations of the organic matrix. This is of important clinical interest because it helps to find therapeutic approaches directly targeting the primary etiological defects to correct the patients' BMDD towards normal BMDD. PMID- 17337262 TI - Wnt gene expression in the post-natal growth plate: regulation with chondrocyte differentiation. AB - Longitudinal growth of long bones occurs at the growth plate by endochondral ossification. In the embryonic mouse, this process is regulated by Wnt signaling. Little is known about which members of the Wnt family of secreted signaling proteins might be involved in the regulation of the postnatal growth plate. We used microdissection and real-time PCR to study mRNA expression of Wnt genes in the mouse growth plate. Of the 19 known members of the Wnt family, only six were expressed in postnatal growth plate. Of these, Wnts -2b, -4, and -10b signal through the canonical beta-catenin pathway and Wnts -5a, -5b, and -11 signal through the noncanonical calcium pathway. The spatial expression for these six Wnts was remarkably similar, showing low mRNA expression in the resting zone, increasing expression as the chondrocytes differentiated into the proliferative and prehypertrophic state and then (except Wnt-2b) decreasing expression as the chondrocytes underwent hypertrophic differentiation. This overall pattern is broadly consistent with previous studies of embryonic mouse growth cartilage suggesting that Wnt signaling modulates chondrocyte proliferation and hypertrophic differentiation. We also found that mRNA expression of these Wnt genes persisted at similar levels at 4 weeks, when longitudinal bone growth is waning. In conclusion, we have identified for the first time the specific Wnt genes that are expressed in the postnatal mammalian growth plate. The six identified Wnt genes showed a similar pattern of expression during chondrocyte differentiation, suggesting overlapping or interacting roles in postnatal endochondral bone formation. PMID- 17337264 TI - Conformation of a double-membrane-spanning fragment of a G protein-coupled receptor: effects of hydrophobic environment and pH. AB - Overcoming the problems associated with the expression, purification and in vitro handling of membrane proteins requires an understanding of the factors governing the folding and stability of such proteins in detergent solutions. As a sequel to our earlier report (Biochim. Biophys. Acta 1747(2005), 133-140), we describe an improved purification procedure and a detailed structural analysis of a fragment of the mu-opioid receptor ('TM2-3') that comprises the second and third transmembrane segments and the extracellular loop that connects them. Circular dichroism (CD) spectroscopy of TM2-3 in 2,2,2-trifluoroethanol gave a helical content similar to that predicted by published homology models, while spectra acquired in several detergents showed significantly lower helical contents. This indicates that this part of the mu-opioid receptor has an intrinsic propensity to be highly helical in membrane-like environments, but that in detergent solutions, this helical structure is not fully formed. Proteolysis of TM2-3 with trypsin showed that the helical portions of TM2 and TM3 are both shorter than their predicted lengths, indicating that helix-helix interactions in the full-length receptor are apparently important for stabilizing their conformation. Lengthening the alkyl chain of the detergent led to a small but significant increase in the helicity of TM2-3, suggesting that hydrophobic mismatch could play an important role in the stabilization of transmembrane helices by detergents. Protonation of aspartic acid residues in detergent-solubilized TM2-3 also caused a significant increase in helicity. Our results thus suggest that detergent alkyl chain-length and pH may influence membrane protein stability by modulating the stability of individual transmembrane segments. PMID- 17337265 TI - Serum amyloid P component induces TUNEL-positive nuclei in rat brain after intrahippocampal administration. AB - Serum amyloid P component (SAP)-induced neuronal apoptosis has been demonstrated on the primary culture of embryonic rat cerebral cortex in vitro. Here we present pieces of evidence that cell death is also induced by serum amyloid P component in living rat brain similarly to that in cell culture. Intrahippocampally administered SAP diffuses from the site of injection to the cortical and subcortical area of the rat brain and enters the cells of brain tissue in 1 week. It induces elevation of the number of in situ TdT-mediated dUTP-X nick end labeled nuclei in the hippocampus, cortex and subcortical structures of rat central nervous system. DNA fragmentation, which is detected by the end labeling reaction, is characteristic to apoptosis. It develops in 4 weeks following exposure. Apoptosis is an important form of cell death in different neurodegenerative diseases including Alzheimer's disease. Our present work reveals that apoptosis can be induced by SAP beyond other hitherto known apoptosis inducing components of neurodegeneration. Hereby SAP seems to be an important component of the process, which leads to expanded neuronal loss in the pathomechanism of neurodegenerative diseases. PMID- 17337266 TI - Raloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes. AB - The selective estrogen receptor modulator raloxifene is widely used in the treatment of postmenopausal osteoporosis, and has cardioprotective properties. However, effects of raloxifene on cardiac ion channels are unclear. The present study was designed to investigate the effects of raloxifene and beta-estradiol on transient outward and ultra-rapid delayed rectifier potassium currents (Ito1 and IKur) in human atrial myocytes with a whole cell patch-clamp technique. Ito1 was inhibited by raloxifene in a concentration-dependent manner with an IC50 of 0.9 microM. Raloxifene at 1 microM decreased Ito1 by 40.2+/-1.9% (at +50 mV, n=14, P<0.01 vs control). Time-dependent recovery from inactivation was slowed, and time to peak and time-dependent inactivation of Ito1 were significantly accelerated, while steady-state voltage dependent activation and inactivation of Ito1 were not affected by raloxifene. In addition, raloxifene remarkably suppressed IKur (IC50=0.7 microM). Raloxifene at 1 microM decreased IKur by 57.3+/-3.3% (at +50 mV, n=10, P<0.01 vs control). However, beta-estradiol inhibited Ito1 (IC50=10.3 microM) without affecting IKur. The inhibitory effects of raloxifene and beta-estradiol on Ito1 and/or IKur were unaffected by the estrogen receptor antagonist ICI 182,780. Our results indicate that raloxifene directly inhibits the human atrial repolarization potassium currents Ito1 and IKur. Whether raloxifene is beneficial for supraventricular arrhythmias remains to be studied. PMID- 17337267 TI - Immunomodulatory properties of increased levels of liver X receptor beta in peripheral blood mononuclear cells from multiple sclerosis patients. AB - Liver X receptors (LXRalpha and LXRbeta) are nuclear transcription factors that inhibit transcription of genes of inflammation while inducing HMGCoA reductase. In this paper we demonstrate increased mRNA levels of LXRbeta in peripheral blood mononuclear cells (PBMCs) from multiple sclerosis patients with respect to other neurological patients and healthy controls (HC) (p<0.01). Agonist-induced activation of LXRs partially counteracts the anti-CD3+ anti-CD28-induced proliferation of T cells (p<0.01) and secretion of IFNgamma (p<0.001) from PBMCs of MS patients as well as of HC. Secretion of IL-4 is not affected. Our findings suggest that regulation of cholesterol metabolism not strictly related to inhibition of HMGCoA reductase can modulate activity of lymphocytes in MS. PMID- 17337268 TI - An on-line modified least-mean-square algorithm for training neurofuzzy controllers. AB - The problem hindering the use of data-driven modelling methods for training controllers on-line is the lack of control over the amount by which the plant is excited. As the operating schedule determines the information available on-line, the knowledge of the process may degrade if the setpoint remains constant for an extended period. This paper proposes an identification algorithm that alleviates "learning interference" by incorporating fuzzy theory into the normalized least mean-square update rule. The ability of the proposed methodology to achieve faster learning is examined by employing the algorithm to train a neurofuzzy feedforward controller for controlling a liquid level process. Since the proposed identification strategy has similarities with the normalized least-mean-square update rule and the recursive least-square estimator, the on-line learning rates of these algorithms are also compared. PMID- 17337269 TI - Towards an alternative to Benner's theory of expert intuition in nursing: a discussion paper. AB - Several authors have highlighted the role of intuition in expertise. In particular, a large amount of data has been collected about intuition in expert nursing, and intuition plays an important role in the influential theory of nursing expertise developed by Benner [1984. From Novice to Expert: Excellence and Power in Clinical Nursing Practice. Addison-Wesley, Menlo Park, CA]. We discuss this theory, and highlight both data that support it and data that challenge it. Based on this assessment, we propose a new theory of nursing expertise and intuition, which emphasizes how perception and conscious problem solving are intimately related. In the discussion, we propose that this theory opens new avenues of enquiry for research into nursing expertise. PMID- 17337270 TI - ApoB/apoA-I ratio is related to femoral artery plaques in 64-year-old women also in cases with low LDL cholesterol. AB - INTRODUCTION: The apolipoproteinB (apoB)/apolipoproteinA-I (apoA-I) ratio mirrors the number of pro-atherogenic and anti-atherogenic lipoprotein particles. This ratio may carry more information on risk for atherosclerosis than LDL in cohorts with impaired glucose tolerance. The aim was to examine the association between the apoB/apoA-I ratio and ultrasound-assessed atherosclerosis in the carotid and femoral arteries in women with varying degrees of glucose tolerance. METHODS: Plaque occurrence, and intima-media thickness in the carotid and femoral arteries were examined by B-mode ultrasound in a random sample of 64-year-old women (n=646) living in Gothenburg, Sweden, representing different degrees of glucose intolerance (diabetes (n=234), impaired (n=212) and normal glucose tolerance (n=200)). Traditional risk factors and serum concentrations of apolipoproteins were analysed. RESULTS: For subjects in the lowest LDL tertile, the risk of having a plaque in the femoral artery was three times greater for subjects in the highest apoB/apoA-I tertile compared to subjects in the lowest tertile (OR: 3.0, 95% CI: 1.2-7.5). A clear increase in the occurrence of femoral plaque was observed already at a cut-off value of 0.63 (OR: 1.8, 95% CI: 1.2-2.6). ApoB/apoA I was also related to femoral plaque occurrence in women with low HbA1c. ApoB/A-I ratio was associated with carotid and femoral IMT but not carotid plaques. CONCLUSION: The apoB/apoA-I ratio improved the identification of cases with femoral artery atherosclerosis in a cohort of women with varying degrees of glucose tolerance. Such cases could also be identified in women with normal LDL and HbA1c levels. The results indicate that an apoB/apoA-I ratio above 0.63 should be used as a marker of increased risk. PMID- 17337271 TI - Methods for comparing the diversity of samples of the T cell receptor repertoire. AB - Analysis of T cell receptor (TCR) data has become a crucial element in many studies aimed at better understanding the evolution of the T cell repertoire and the role of TCR diversity in immune responses. In this paper we focus on comparing the diversity between samples of the TCR repertoire. We discuss some of the limitations and potential problems inherent in some of the more popular approaches to comparing samples of the TCR repertoire and we suggest alternate methods that both avoid these problems and enrich the analysis of TCR data. Examples from published studies of the CD8(+) T cell responses to the influenza A virus D(b)NP(366) and D(b)PA(224) epitopes in mice are used to demonstrate the implementation of these methods. One example involves a comparison between the central and effector memory T cell subsets, defined on the basis of CD62L expression, and the other examines changes in the TCR repertoire over time. PMID- 17337272 TI - A comparison of stigmatellin conformations, free and bound to the photosynthetic reaction center and the cytochrome bc1 complex. AB - We describe in detail the conformations of the inhibitor stigmatellin in its free form and bound to the ubiquinone-reducing (Q(B)) site of the reaction center and to the ubiquinol-oxidizing (Q(o)) site of the cytochrome bc(1) complex. We present here the first structures of a stereochemically correct stigmatellin in complexes with a bacterial reaction center and the yeast cytochrome bc1 complex. The conformations of the inhibitor bound to the two enzymes are not the same. We focus on the orientations of the stigmatellin side-chain relative to the chromone head group, and on the interaction of the stigmatellin side-chain with these membrane protein complexes. The different conformations of stigmatellin found illustrate the structural variability of the Q sites, which are affected by the same inhibitor. The free rotation about the chi1 dihedral angle is an essential factor for allowing stigmatellin to bind in both the reaction center and the cytochrome bc1 pocket. PMID- 17337273 TI - Concordance between epidermal nerve fiber density and sensory examination in patients with symptoms of idiopathic small fiber neuropathy. AB - Quantitation of epidermal nerve fiber (ENF) density is an objective diagnostic test of small fiber neuropathy (SFN). For a diagnostic test to be clinically useful it should correspond well with clinically meaningful physical findings. We performed a retrospective analysis of the concordance between foot ENF density and clinical findings in all patients seen at our institution with possible idiopathic SFN who underwent skin biopsy for ENF density determination. We found a high concordance between reduced foot ENF density and loss of pinprick sensitivity in this patient population. Our findings indicate that ENF density determination is a clinically relevant objective test in patients undergoing evaluation for possible SFN. PMID- 17337274 TI - The incomplete nature of multiple sclerosis relapse resolution. AB - Relapsing-remitting multiple sclerosis (RRMS) is often associated with accrual of disability, even though it precedes the progressive phase of the disease, in which clinical disability is most apparent. Changes in T1 and T2 magnetic resonance imaging (MRI) findings, as well as clinical trials of drugs that target RRMS, have established correlations between relapse episodes and disability progression. Briefly reviewed herein are relevant data that link relapses with disability accrual, including a recent direct analysis of well-defined clinical trial databases that shows MS relapses to have a measurable and sustained effect on disability. These studies pinpoint the measurable residual deficits of relapses that had, up to this point, only been implied by prior research, confirming the existence of relapse-associated step-wise worsening in patients with RRMS and lending credence to the continued development of long-term treatment targeted at the early phases of the disorder. PMID- 17337275 TI - Validation of PDQ-8 as an independent instrument in English and Chinese. AB - Previous validation studies on the PDQ-8, a brief disease-specific quality of life instrument, were performed with the PDQ-8 nested in the original PDQ-39. Such an approach may influence patient responses and the psychometric properties of the PDQ-8. We therefore undertook this study to validate the PDQ-8 when administered independently in English and Chinese and found good item-to-scale correlations (correlation coefficient: 0.44-0.68) and internal consistency (Cronbach's alpha: 0.81, 0.87). Factor analyses yielded a component on which all 8 questions were substantially loaded (loading range: 0.55-0.77). Scree plots also showed the one-factor solution thereby validating the PDQ-8 summary index. Construct validation against the Hoehn and Yahr stage and UPDRS motor scores showed significant correlations between higher PDQ-8 summary index and increased disease severity in both English and Chinese versions. Our results show the PDQ-8 to be a valid and reliable disease-specific HRQoL instrument for PD when used independently of the PDQ-39. PMID- 17337276 TI - Dynamic patterns of gene regulation I: simple two-gene systems. AB - Regulation of gene activities is studied by means of computer assisted mathematical analysis of ordinary differential equations (ODEs) derived from binding equilibria and chemical reaction kinetics. Here, we present results on cross-regulation of two genes through activator and/or repressor binding. Arbitrary (differentiable) binding function can be used but systematic investigations are presented for gene-regulator complexes with integer valued Hill coefficients up to n=4. The dynamics of gene regulation is derived from bifurcation patterns of the underlying systems of kinetic ODEs. In particular, we present analytical expressions for the parameter values at which one-dimensional (transcritical, saddle-node or pitchfork) and/or two-dimensional (Hopf) bifurcations occur. A classification of regulatory states is introduced, which makes use of the sign of a 'regulatory determinant'D (being the determinant of the block in the Jacobian matrix that contains the derivatives of the regulator binding functions): (i) systems with D<0, observed, for example, if both proteins are activators or repressors, to give rise to one-dimensional bifurcations only and lead to bistability for n>or=2 and (ii) systems with D>0, found for combinations of activation and repression, sustain a Hopf bifurcation and undamped oscillations for n>2. The influence of basal transcription activity on the bifurcation patterns is described. Binding of multiple subunits can lead to richer dynamics than pure activation or repression states if intermediates between the unbound state and the fully saturated DNA initiate transcription. Then, the regulatory determinant D can adopt both signs, plus and minus. PMID- 17337277 TI - Continuation and bifurcation analysis of a periodically forced excitable system. AB - The response of an excitable cell to periodic electrical stimulation is modeled using the FitzHugh-Nagumo (FHN) system submitted to a gaussian-shaped pacing, the width of which is small compared with the action potential duration. The influence of the amplitude and the period of the stimulation is studied using numerical continuation and bifurcation techniques (AUTO97 software). Results are discussed in the light of prior experimental and theoretical findings. In particular, agreement with the documented behavior of periodically stimulated cardiac cells and squid axons is discussed. As previously reported, we find many different "M:N" periodic solutions, period-doubling sequences leading to seemingly chaotic regimes, and bistability phenomena. In addition, the use of continuation techniques has allowed us to track unstable solutions of the system and thus to determine how the different stable rhythms are connected with each other in a bifurcation diagram. Depending on the stimulus amplitude, the aspect of the bifurcation diagram with the stimulus period as main varying parameter can vary from very simple to very complex. In its most developed structure, this bifurcation diagram consists of a main "tree" of period-2(P) branches, where the 1:1, 1:0, 2:2, 2:1,... rhythms are located, and of several closed loops made up of period-{N x 2(P)} branches (N>2), isolated from each other and from the main tree. It is mainly on such loops that N:1 rhythms (N>2) on one hand, and N:N-1 or Wenckebach rhythms (N>2) on the other hand, are located. Stable M:N and M:N-1 rhythms (M>or=N) can be found on the same branch of solutions. They are separated by a region of unstable solutions at small stimulus amplitudes, but this region shrinks gradually as the stimulus amplitude is raised, until it finally disappears. We believe that this property is related to the excitability characteristics of the FHN system. It would be interesting to know if it has any correspondence in the behavior of real excitable cells. PMID- 17337278 TI - Protective effect of radicicol against LPS/IFN-gamma-induced neuronal cell death in rat cortical neuron-glia cultures. AB - We investigated the protective activity of radicicol, an antifungal antibiotic, against inflammation-induced neurotoxicity in neuron-glia cultures. Radicicol potently prevented the loss of neuronal cell bodies and neurites from LPS/IFN gamma-induced neurotoxicity in rat cortical neuron-glia cultures with an EC(50) value of 0.09 microM. Radicicol inhibited the LPS/IFN-gamma-induced expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO) in microglia. Additionally, radicicol decreased the LPS/IFN-gamma-induced release of tumor necrosis factor-alpha (TNF-alpha) in the cultures. The inhibitory potency of radicicol against the production of NO and TNF-alpha was well correlated with the protection of neurons. These results suggest that the protective effect of radicicol against LPS/IFN-gamma-induced neuronal cell death in neuron-glia cultures is mediated via the inhibition of TNF-alpha release, as well as the suppression of iNOS expression in microglia. PMID- 17337279 TI - Effects of luteolin on learning acquisition in rats: involvement of the central cholinergic system. AB - The study was conducted to investigate the ameliorating effects of luteolin on memory acquisition in rats. The effects of luteolin on scopolamine-induced impairment of passive avoidance response were evaluated primarily, as well as the role of the central nervous system through the use of central neurotoxins and central nervous antagonists. Luteolin was not reversed by scopolamine N methylbromide (M-SCOP) but blocked the impairment of learning acquisition induced by cholinergic neurotoxin (ethylcholine aziridinium, AF64A) and muscarinic (scopolamine hydrobromide, SCOP) and nicotinic (mecamylamine, MECA) receptor antagonists. However, it did not block dopaminergic neurotoxin (6 hydroxydopamine, 6-OHDA)-induced and serotonergic neurotoxin (5,7 dihydroxytryptamine, 5,7-DHT)-induced impairments. From these results, we suggest that the attenuating effect of luteolin (10 mg/kg, i.p.) on the deficits of passive avoidance performance induced by SCOP may be related to the increases in the activities of central muscarinic and nicotinic receptors. PMID- 17337280 TI - A novel cyathane diterpene, cyrneine A, induces neurite outgrowth in a Rac1 dependent mechanism in PC12 cells. AB - We examined the effects of cyrneine A, a novel diterpene isolated from the mushroom Sarcodon cyrneus, on morphology of rat pheochromocytoma cells (PC12). In response to cyrneine A, PC12 cells extended their neurites, an effect partially blocked by the extracellular signal-regulated kinase (ERK) kinase inhibitor PD98059, but not by the protein kinase C inhibitor GF109203X, nor the phosphatidylinositol-3-kinase inhibitor wortmannin. Cyrneine A did not activate ERK at any of the time points tested (5-120 min), indicating that only the basal activity of ERK is required for cyrneine A-induced neurite outgrowth. As transcriptional regulation is required for neurite extension, the activity of three major transcription factors was determined. Cyrneine A enhanced activation of the transcription factors activator protein-1 (AP-1) and nuclear factor kappaB, but not CREB, and this was accompanied by enhanced c-fos expression. Moreover, we determined the role of Rac1, a small GTPase protein of the Rho family that regulates actin dynamics, in cyrneine A-induced neurite outgrowth. Treatment with cyrneine A led to actin translocation and subsequently, to accumulation of F-actin at the tip of neurites. Rac1 activity was increased by cyrneine A and expression of a dominant-negative Rac1 mutant significantly inhibited the cyrneine A-induced extension of neurites. These results suggest that cyrneine A induces neurite outgrowth in a Rac1-dependent mechanism. PMID- 17337281 TI - Expression of muscarinic and nicotinic acetylcholine receptors in the mouse urothelium. AB - Acetylcholine (ACh) and its receptors play a crucial role in bladder physiology. Here, we investigated the presence of muscarinic receptor subtypes (MR) and nicotinic acetylcholine receptor (nAChR) alpha-subunits in the mouse urothelium by RT-PCR and immunohistochemistry. With RT-PCR, we detected mRNAs coding for all of the five different MR subtypes and for the nicotinic receptor subunits alpha2, alpha4, alpha5, alpha6, alpha7, alpha9 and alpha10, whereas the alpha3-subunit was not expressed. Using immunohistochemistry, we localised a panel of acetylcholine receptors in the different layers of the murine bladder urothelium, with predominant appearance in the basal plasma membrane of the basal cell layer and in the apical membrane of the umbrella cells. M2R and subunit alpha9 were observed exclusively in the umbrella cells, whereas the MR subtypes 3-5 and the nAChR subunits alpha4, alpha7 and alpha10 were also detected in the intermediate and basal cell layers. The subunit alpha5 was localised only in the basal cell layer. In conclusion, the murine urothelium expresses multiple cholinergic receptors, including several subtypes of both MR and nAChR, which are differentially distributed among the urothelial cell types. Since these receptors have different electrophysiological and pharmacological properties, and therefore are considered to be responsible for different cellular responses to ACh, this differential distribution is expected to confer cell type-specificity of cholinergic regulation in the bladder urothelium. PMID- 17337282 TI - Computation of spiking activity for a stochastic spatial neuron model: effects of spatial distribution of input on bimodality and CV of the ISI distribution. AB - We obtain computational results for a new extended spatial neuron model in which the neuronal electrical depolarization from resting level satisfies a cable partial differential equation and the synaptic input current is also a function of space and time, obeying a first order linear partial differential equation driven by a two-parameter random process. The model is first described explicitly with the inclusion of all biophysical parameters. Simplified equations are obtained with dimensionless space and time variables. A standard parameter set is described, based mainly on values appropriate for cortical pyramidal cells. When the noise is small and the mean voltage crosses threshold, a formula is derived for the expected time to spike. A simulation algorithm, involving one-dimensional random processes is given and used to obtain moments and distributions of the interspike interval (ISI). The parameters used are those for a near balanced state and there is great sensitivity of the firing rate around the balance point. This sensitivity may be related to genetically induced pathological brain properties (Rett's syndrome). The simulation procedure is employed to find the ISI distribution for some simple patterns of synaptic input with various relative strengths for excitation and inhibition. With excitation only, the ISI distribution is unimodal of exponential type and with a large coefficient of variation. As inhibition near the soma grows, two striking effects emerge. The ISI distribution shifts first to bimodal and then to unimodal with an approximately Gaussian shape with a concentration at large intervals. At the same time the coefficient of variation of the ISI drops dramatically to less than 1/5 of its value without inhibition. PMID- 17337283 TI - Was John Reid right? Smoking, class, and pleasure: a population-based cohort study in England. AB - OBJECTIVES: To assess whether there is a relationship between smoking and levels of overall quality of life, or with the pleasure domain of quality of life, in lower socio-economic groups (SES). STUDY DESIGN: Cohort study involving 9176 individuals aged 50 years and over who participated in the Health Survey for England and were followed up in Wave 1 of the English Longitudinal Study of Ageing in 2002. METHODS: We classified smokers as never-smokers, ex-smokers and current smokers, and used household wealth as a marker for socio-economic position. Pleasure was assessed using the pleasure subscale of the CASP-19 instrument, a 19-point measure of quality of life that covers four theoretical domains: control, autonomy, self-realization and pleasure. RESULTS: We found that the odds ratio for experiencing lower than median levels of pleasure for smokers with low SES was 1.42 (95% CI 1.16-1.74), and for all smokers was 1.33 (95% CI 1.17-1.51). The same pattern of associations was found when the outcome was total CASP-19 score or positive GHQ-12 score. CONCLUSIONS: We found no evidence to support a claim that smoking is associated with heightened levels of pleasure, either in people with low SES or in the general population. In fact, our results suggest the opposite: that smoking is associated with lower levels of pleasure and poorer overall quality of life. Policy decisions on smoking should consider its potentially harmful effect on quality of life and pleasure as well as on other aspects of health. PMID- 17337284 TI - Characteristics of daily and occasional smoking among youths. AB - OBJECTIVES: The purpose of this study was to develop a more detailed understanding of the characteristics of occasional smokers, and how the characteristics of occasional smokers differ from those of daily smokers. This information can then be used in youth smoking programmes to better address these differences in a manner that would target appropriate youth with appropriate cessation methods. METHODS: A questionnaire was administered to 976 university students, aged between 18 and 25 years, in Ankara, Turkey. The topics covered included age, sex and tobacco use characteristics. Daily and occasional smokers were defined according to traditional definitions of smoking. RESULTS: Among the 976 students surveyed, 482 (49.4%) reported being active smokers. Among these smokers, 199 (41.3%) were classified as occasional smokers and 283 (58.7%) were daily smokers using the traditional definitions of smoking. Many of the active smokers had relatives or friends who also smoked, specifically, 46.5% had a father who smokes, 13.3% had a mother who smokes, 26.8% had an older brother or sister who smokes, and 69.7% had two or more close friends who smoke. Although more than 51.3% of smokers planned on quitting smoking, only 26.1% had previously tried to quit smoking but 64.7% believed they could successfully quit. Daily smokers reported that they made fewer attempts to quit smoking than occasional smokers. More often than occasional smokers, daily smokers reported that they smoke because they like the image, they are addicted, smoking relieves stress and/or their friends smoke. Occasional smokers reported that they smoke less at home or at the university than in other places, and smoke more often with friends than when alone or with family members. This pattern is encouraged by the family structure in Turkish society, where smoking by adolescents at home in the presence of family members is frowned upon. CONCLUSIONS: This study demonstrates substantial differences between occasional and daily smokers. If effective future smoking prevention and cessation programmes that target youth are going to be developed, data like those gathered in this study are critical. Basic information regarding cigarette consumption patterns, while important, is insufficient to understand behaviour and key factors that trigger smoking among the youth population. PMID- 17337286 TI - Evidence for higher biomagnification factors of lower chlorinated PCBs in cultivated seabass. AB - Thirty three PCB congeners were analyzed in three size classes of seabass (Dicentrarchus labrax), from a semi-intensive fish farm, in food and in abiotic compartment. Water and suspended particulated matter (SPM) showed higher concentrations of lower chlorinated PCBs, whereas fish tissues and food showed higher concentrations of CB153 and CB138. In order to examine the influence of different inputs to seabass contamination, bioaccumulation factors (BAF), biota suspended particulate matter bioaccumulation factors (BSMAF) and biomagnification factors (BMF) were calculated. In general, the log BAF and log BSMAF showed good correlations with log K(ow), for congeners with log K(ow)>6.1. In three fish size classes, PCB congeners with log K(ow)<6.1 were found at concentrations higher than what was expected based on the BAF calculated for the more hydrophobic congeners, suggesting a different contribution of sources. The application of a mass balance model for accumulation of some congeners in seabass estimated concentrations in fish 3- to 38-fold higher than the measured values, probably by overestimating gill absorption. The model was applied with other scenarios in order to maximize uptake from food, which may have a significant influence in accumulation, and not only from diet pellets. Its contribution to fish contamination for highly chlorinated PCBs may reach a maximum of 54-64%, and for lower chlorinated PCBs its contribution is lower than 20%. In this work it was proved that to reduce fish contamination the quality of the water should be controlled. PMID- 17337285 TI - Identification of an immunodominant CD4+ T cell epitope in the VP6 protein of rotavirus following intranasal immunization of BALB/c mice. AB - The only lymphocytes required for protection against fecal rotavirus shedding after intranasal immunization of BALB/c (H-2(d)) mice with a chimeric rotavirus VP6 protein (MBPColon, two colonsVP6) and the mucosal adjuvant LT(R192G) are CD4(+) T cells. The purpose of this study was to identify CD4(+) T cell epitopes within VP6 that might be responsible for this protection. To make this determination, spleen cells obtained from BALB/c mice following intranasal immunization with MBPColon, two colonsVP6/LT(R192G) were stimulated in vitro with either MBPColon, two colonsVP6 or overlapping VP6 peptides containing 29.9 microg/g (14%, 20%, 40%, and 28%, respectively). Similarly, the prevalence rates of mouse allergen-specific IgG and IgG(4) did not increase across increasing exposure categories. Mouse allergen-specific IgG and IgG(4) were strongly associated with IgE sensitization (odds ratios [95% CI], 82.8 [20.5-334.4] and 50.4 [14.0-181.7], respectively). CONCLUSION: High-level exposure to mouse allergen in children may be associated with attenuated humoral responses of all isotypes rather than selective attenuation of IgE. CLINICAL IMPLICATIONS: Protection against allergic sensitization by high-dose allergen exposure may not be mediated by preferential production of IgG over IgE. PMID- 17337297 TI - Allergen immunotherapy: where is it now? AB - The scientific basis and the proof of clinical effectiveness of allergen immunotherapy administered by subcutaneous injection (SCIT) are well established. It is effective treatment for sensitivity to Hymenoptera venom and for allergic rhinitis and allergic asthma. SCIT administered in the proper setting reduces the development of new sensitivities and progression from rhinitis to asthma. Further, the beneficial effects persist long after completion of a course of treatment. Although many people enjoy the benefits of SCIT, extension of its use to the many others who might be candidates for this treatment is limited by its drawbacks of safety concerns and the inconvenience of repeated clinic visits over several years to receive the injections. There are many attempts underway to improve on the safety and convenience while still retaining the benefits of SCIT. These include approaches using current allergen extracts, especially by administering them sublingually. Alternatively, through recombinant technology, extracts are being modified to reduce their allergenicity without reducing their immunogenicity. They are being linked to immunostimulatory DNA sequences that will modify their in vivo processing resulting in an enhanced nonallergic response or they are being incorporated into fusion proteins with inhibitory properties for mast cells and basophils. PMID- 17337298 TI - Characterization of allergens from the fish bait Galleria mellonella. PMID- 17337299 TI - Inhibitory receptors on eosinophils: a direct hit to a possible Achilles heel? AB - Since their discovery, much data have been accumulated on eosinophil differentiation, morphology, trafficking, and anatomical location(s) in health and disease. Although "classic" activation pathways (such as cytokines, chemokines, proinflammatory components, and adhesion molecules) regulating eosinophil activation have been widely explored, the presence of other activation molecules that might be disease specific is limited. Furthermore, the expression and function of inhibitory receptors on eosinophils have received scant attention. The need to identify new pathways that regulate eosinophil activation is a crucial goal as it can expand our knowledge on this peculiar cell and provide insights into important queries regarding the physiologic function of eosinophils. Over the past several years, it has become increasingly apparent that eosinophils express several receptors belonging to the immunoglobulin superfamily. In this review, we summarize the current knowledge on the expression and function of new pathways that govern eosinophil activation. In addition, we will propose some hypotheses regarding the ability to use these pathways as a future therapeutic approach. In conclusion, we assume that targeting inhibitory receptors on eosinophils may provide opportunities for immunoregulatory therapy in the near future. PMID- 17337300 TI - SPR microscopy and its applications to high-throughput analyses of biomolecular binding events and their kinetics. AB - Surface plasmon resonance (SPR) sensing has long been used to study biomolecular binding events and their kinetics in a label-free way. This approach has recently been extended to SPR microscopy, which is an ideal tool for probing large microarrays of biomolecules for their binding interactions with various partners and the kinetics of such binding. Commercial SPR microscopes now make it possible to simultaneously monitor binding kinetics on >1300 spots within a protein microarray with a detection limit of approximately 0.3 ng/cm(2), or <50 fg per spot (<1 million protein molecules) with a time resolution of 1s, and spot-to spot reproducibility within a few percent. Such instruments should be capable of high-throughput kinetic studies of the binding of small ( approximately 200 Da) ligands onto large protein microarrays. The method is label free and uses orders of magnitude less of the precious biomolecules than standard SPR sensing. It also gives the absolute bound amount and binding stoichiometry. PMID- 17337301 TI - Dual in vitro perfusion of an isolated cotyledon as a model to study the implication of changes in the third trimester placenta on preeclampsia. AB - In the current study perfusions of an isolated cotyledon of term placenta using standard medium were compared to medium containing xanthine plus xanthine oxidase (X+XO), which generates reactive oxygen species (ROS). A time-dependant increase in the levels of different cytokines (TNF-alpha, IL-1ss, IL-6, IL-8 and IL-10) was observed between 1 and 7h with more than 90% of the total recovered from the maternal compartment with no significant difference between the 2 groups. For 8 iso-PGF2alpha 90% of the total was found in the fetal compartment and a significantly higher total release was seen in the X+XO group. Microparticles (MPs) isolated from the maternal circuit were identified by flow cytometry as trophoblastic sheddings, whereas MPs from the fetal circuit were predominantly derived from endothelial cells. More than 90% of the total of MPs was found in the maternal circuit. The absolute amount of the total as well as the maternal fraction were significantly higher in the X+XO group. Immunohistochemistry (IHC) of the perfused tissue revealed staining for IL-1beta of villous stroma cells, which became clearly more pronounced in experiments with X+XO. Western blot of tissue homogenate revealed 2 isoforms of IL-1beta at 17 and 31kD. In X+XO experiments there was a tendency for increased expression of antioxidant enzymes in the tissue. Western blot of MPs from the maternal circuit showed increased expression of antioxidant enzymes in the X+XO group and for IL-1beta only the 17kD band was detected. In vitro reperfusion of human placental tissue results in mild tissue injury suggestive of oxidative stress. In view of the increased generation of ROS in perfused tissue with further increase under the influence of X+XO, the overall manifestation of oxidative stress remained rather mild. Preservation of antioxidant capacity of human placental tissue could be a sign of integrity of structure and function being maintained in vitro by dual perfusion of an isolated cotyledon. The observed changes resemble findings seen in placentae from preeclampsia. PMID- 17337302 TI - Gangliosides, Ab1 and Ab2 antibodies IV. Dominance of VH domain in the induction of anti-idiotypic antibodies by gene gun immunization. AB - The heavy chain of anti-N-glycolyl-ganglioside P3 mAb plays the main role in its binding properties. At least one hybrid idiotype consisting on the P3 VH and an unrelated VL domain retains antigen recognition. Moreover, the unusual immunogenic properties of P3 idiotype could be modified by single mutations of H CDR residues. Here, we show that DNA gene gun immunization with the P3 VH combined with an unrelated VL domain or with itself (VH dimer, VHD) is enough for inducing anti-idiotypic antibodies, independently of antigen recognition by the resulting molecule. The scFv fragment of P3 mAb was also able to induce an anti idiotypic response. For both the P3 and the P3 anti-idiotypic 1E10 mAbs, heavy chains dominate the induction of antibodies against the respective idiotypes. PMID- 17337303 TI - Comparison of a new gold-immunochromatographic assay for the detection of antibodies against avian influenza virus with hemagglutination inhibition and agar gel immunodiffusion assays. AB - A gold-immunochromatographic test-strip kit is used for the detection of IgG antibodies against the nucleocapsid protein of Avian Influenza Virus (AIV). Compared with the "gold standard", i.e. hemagglutination inhibition (HI) and agar gel immunodiffusion (AGID) assays, the gold-immunochromatographic test strip has many advantages, such as high specificity, high sensitivity, convenience, is rapid and has low cost. The gold-immunochromatographic test strip provides a unique tool for the on-site surveillance and diagnosis of Avian Influenza. PMID- 17337304 TI - Immune responses to an Eimeria acervulina infection in different broilers lines. AB - The (T-cell) immune responses of two different broiler lines to a primary Eimeria acervulina infection were investigated. The lines used were a commercial fast growing broiler line and a slow-growing type of broiler as used in organic farming. Seven-day-old broilers of both lines were infected with 5 x 10(4) oocysts of E. acervulina. The animals were weighed and a species-specific real time PCR was used to quantify the total amount of parasites in the duodenum. In the fast-growing line, a lower parasite load was seen from day 4 onwards compared to the slow-growing line. In both lines the intestinal peak of Eimeria DNA was observed at day 5 post infection (p.i.). In the duodenum no increase in CD4(+) T cells was found in both infected lines, but a fast increase in CD8(+) T-cells was observed in the fast-growing line. At day 3 p.i. in the slow-growing broilers an IL-18 mRNA response was observed. At day 4 p.i. strong IFN-gamma and IL-8 mRNA responses were found in both lines. No IL-4 mRNA responses were found in the duodenum. In conclusion, both lines have different growth rates and control and infected conditions. Based on the kinetics of observed phenomena a primary infection with E. acervulina in 7-day-old broilers seems to generate an early CD8alpha(+) response in fast-growing broilers compared to the slow-growing broilers. This difference in immune reaction after an E. acervulina infection could result in a different Eimeria load in the duodenum. PMID- 17337305 TI - Effects of orbitofrontal, infralimbic and prelimbic cortical lesions on serial spatial reversal learning in the rat. AB - BACKGROUND: Recent evidence suggests that the neural correlates of reversal learning are localised to the orbitofrontal cortex whereas studies on the contribution of the medial prefrontal cortex to this capacity have produced equivocal results. This study examines the behavioural effects of selective lesions centred on orbitofrontal, infralimbic and prelimbic cortex on serial spatial reversal learning in the rat. METHODS: Rats were trained on a novel instrumental two-lever spatial discrimination and reversal learning task, measuring both 'cognitive flexibility' and constituent processes including response inhibition. Both levers were presented, only one of which was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a series of reversals was presented. RESULTS: Bilateral excitotoxic lesions of the orbitofrontal cortex did not affect retention of a preoperatively acquired spatial discrimination but did impair reversal learning. This deficit manifested as increased perseverative responding on the previously correct lever. Although impairments were evident during reversal 1, OFC-lesioned animals performed significantly better than controls on reversal 2. There were no significant effects of infralimbic and prelimbic lesions on the retention of a spatial discrimination or reversal learning. CONCLUSIONS: These results indicate that the orbitofrontal cortex is critical for flexible responding in serial spatial reversal learning. The present findings may be relevant to deficits in reversal learning and response inhibition in such neuropsychiatric disorders as obsessive compulsive disorder. PMID- 17337306 TI - ATF-2 stimulates the human insulin promoter through the conserved CRE2 sequence. AB - The insulin promoter contains a number of dissimilar cis-acting regulatory elements that bind a range of tissue specific and ubiquitous transcription factors. Of the regulatory elements within the insulin promoter, the cyclic AMP responsive element (CRE) binds by far the most diverse array of transcription factors. Rodent insulin promoters have a single CRE site, whereas there are four CREs within the human insulin gene, of which CRE2 is the only one conserved between species. The aim of this study was to characterise the human CRE2 site and to investigate the effects of the two principal CRE-associated transcription factors; CREB-1 and ATF-2. Co-transfection of INS-1 pancreatic beta-cells with promoter constructs containing the human insulin gene promoter placed upstream of the firefly luciferase reporter gene and expression plasmids for ATF-2 or CREB-1 showed that ATF-2 stimulated transcriptional activity while CREB-1 elicited an inhibitory effect. Mutagenesis of CRE2 diminished the effect of ATF-2 but not that of CREB-1. ATF-2 was shown to bind to the CRE2 site by electrophoretic mobility shift assay and by chromatin immunoprecipitation, while siRNA mediated knockdown of ATF-2 diminished the stimulatory effects of cAMP related signalling on promoter activity. These results suggest that ATF-2 may be a key regulator of the human insulin promoter possibly stimulating activity in response to extracellular signals. PMID- 17337307 TI - Non-commercial poultry industries: surveys of backyard and gamefowl breeder flocks in the United States. AB - The National Animal Health Monitoring System (NAHMS) Poultry '04 study was conducted to better describe non-commercial United States poultry populations, in particular, backyard and gamefowl breeder flocks. To estimate the density of backyard flocks in close proximity to commercial operations, a sample of 350 commercial poultry operations in 18 top poultry producing states was selected from the National Agricultural Statistics Service (NASS) list of poultry operations. A 1 mile radius circle was drawn around each operation, and door-to door canvassing was conducted within these circles to enumerate premises with all species of birds. Premises with backyard poultry flocks completed a questionnaire focusing on bird health, bird movement, and biosecurity practices. A similar questionnaire, provided in both English and Spanish, was mailed to all members of State affiliates of the United Gamefowl Breeders Association (UGBA) as well as to members of State associations not affiliated with UGBA. An average of 29.4 residences was found within a 1 mile radius of commercial operations, of which 1.9 residences per circle had backyard poultry flocks. Gamefowl breeder flocks were larger, used more health care and biosecurity practices, and moved birds more frequently compared to backyard flocks. PMID- 17337308 TI - Quantification of gene expression of Listeria monocytogenes by real-time reverse transcription PCR: optimization, evaluation and pitfalls. AB - In the current study, various steps in the real-time reverse transcription PCR (real-time RT-PCR) method for determination of RNA expression levels starting from different numbers of Listeria monocytogenes cells were evaluated and optimized. Our results showed that the RNA isolation method as well as the cDNA synthesis may influence the sensitivity of the procedure. For high bacterial cell numbers (10(9) bacterial cells), the RNAqueous kit and the RNeasy Mini kit were equally useful, whereas for low bacterial cell numbers (or=50% were Peak Systolic Velocities of >or=125 cm/s. RESULTS: Preprocedural evaluation of the ipsilateral ECA demonstrated >or=50% stenosis in 32.7% of cases vs 30% contralateral. Both ipsilateral and contralateral 3 (1%) ECA occlusions were noted. After stenting 5 (1.8%) occlusions were seen vs 1% contralateral. No additional ipsilateral occlusions and 2 additional contralateral occlusions were noted at extended follow-up. The prevalence of >or=50% stenosis of the ipsilateral ECA (Kaplan Meier estimates) progressed from 49.1% at 3, to 56.4%, 64.7%, 78.2%, 72.3%, and 74% at 12, 24, 36, 48, and 60 months respectively. Contralateral prevalences were 31.3%, 37.7%, 41.7%, 43.1%, 46.0%, and 47.2% respectively (p<0.001). Progression of stenosis was more pronounced in 234 patients (75%) with overstenting of the carotid bifurcation (p=0.004). CONCLUSION: Our results show that significant progression of >or=50% stenosis in the ipsilateral ECA occurs after CAS. There was greater progression of disease in the ipsilateral compared with the contralateral ECA. Progression of disease in the ECA did not lead to the occurrence of occlusion during follow up. PMID- 17337348 TI - The photodissociation of ozone: a quasi-classical approach to a quantum dynamics problem. AB - It is extremely difficult to execute full quantum dynamics calculations on complex systems (more then three degrees of freedom) due to the exponential increase in computer resources required by these methods. Classical mechanics simulations do not suffer from this problem, but are unable to treat quantum mechanical phenomena such as non-adiabatic effects, which often play a vital role in photochemical processes. A method has been implemented for carrying out dynamical calculations using quasi-classical theory. The time dependent Schrodinger equation is solved using a swarm of trajectories treated under Newtonian laws and Tully's fewest switches trajectory surface hopping is applied to implement the surface switches. The method was applied to ozone, looking at the photodissociation that takes place after excitation into the Chappuis band of the absorption spectrum. While the goal is to treat larger systems, comparison can be made for ozone with numerically exact wavepacket calculations. The method proved successful at calculating quantities such as the rate of population transfer, but there were discrepancies in the details, especially when surface switching occurred from the lower state. PMID- 17337349 TI - Identification of the cuticular lipid composition of the Western Flower Thrips Frankliniella occidentalis. AB - The Western Flower Thrips Frankliniella occidentalis effectively resists many insecticides, but it can be controlled by the use of bioinsecticides such as entomopathogenic fungi. The epicuticular chemistry of these insects is therefore of great interest, and accordingly, the cuticular lipid composition of F. occidentalis was analysed. It was found that the cuticular lipids of both the adult and larval stages of F. occidentalis consist of two groups of compounds- hydrocarbons and free fatty acids. The same hydrocarbon pattern was found in both adults and larvae, with the exception of n-hentriacontane, which was detected only in adult insects. The following homologous series were identified: n-alkanes from C-25 to C-29 (31) with the marked dominance of odd numbers of carbon atoms, 3-methylalkanes with 26 and 28 carbon atoms, and branched monomethylalkanes (branched at C-9, -11, -13 and -15) with 26, 28 and 30 carbon atoms. The chemical composition of the free fatty acids consists of two homologous series: saturated (C(14:0), C(16:0), C(18:0)) and unsaturated fatty acids (C(16:1) and C(18:1)). This analysis confirmed the lack of potential inhibitors of entomopathogenic fungi in the cuticular lipids of this insect species. PMID- 17337350 TI - Chicken liver and muscle carnitine palmitoyltransferase 1: nutritional regulation of messengers. AB - In mammals, carnitine palmitoyltransferase 1 (CPT1) is a rate limiting enzyme of fatty acid oxidation. Two isoforms are present. We characterized a full-length cDNA sequence encoding chicken liver L-CPT1 isoform and a partial cDNA sequence encoding chicken muscle M-CPT1 isoform. CPT1 messengers showed the expected tissue specificity. M-CPT1 messenger and CPT1 activity were higher in oxidative than in glycolytic muscle. Expression of both isoforms was assessed in various tissues of genetically fat or lean chickens. Fasting considerably increased L CPT1 mRNA expression and beta-hydroxyacyl CoA dehydrogenase (HAD) activity in the liver of fat or lean chickens. Unexpectedly, fasting did not increase M-CPT1 mRNA levels nor HAD activity in muscles of either chicken genotype. It however increased succinyl-CoA:3-ketoacid CoA transferase (SCOT) mRNA expression (an enzyme related to ketone body utilization) in oxidative muscle. SCOT messenger was slightly more abundant in oxidative muscle of lean chickens but not in glycolytic muscle. In conclusion, the regulation of fatty acid oxidation is probably not impaired in fat chicken. The absence of fasting stimulation of M CPT1 mRNA expression, which is at variance with the situation observed in mammals, suggests that during fasting, chicken muscles preferentially use ketone bodies as fuel, at least in the short term. PMID- 17337351 TI - 25 mg etanercept once weekly in rheumatoid arthritis and spondylarthropathy. AB - OBJECTIVE: To assess the clinical results at 6 months of etanercept 25 mg once weekly (half-dose), and etanercept 25 mg twice weekly (full-dose), in patients with rheumatoid arthritis or spondylarthropathy. METHODS: Case records of all patients treated by etanercept for at least 6 months in the same rheumatology unit were retrospectively studied, to assess the mean values of DAS-28 and BASDAI, just before (J0), and after 6 months (M6) of treatment, in patients with rheumatoid arthritis or spondylarthropathy treated with etanercept 25 mg given either once or twice weekly. RESULTS: 112 patients had been treated for at least 6 months (44 at half-dose, and 68 at full-dose). Values of DAS-28 or BASDAI both at J0 and M6 were available in 92 patients. DAS-28 dramatically improved both in the half-dose group (from 5.2+/-0.8 to 3.5+/-0.8) and in the full-dose group (from 5.5+/-1.0 to 4.1+/-1.0). BASDAI also strikingly improved both in the half dose group (from 60+/-13 to 25+/-18), and in the full-dose group (from 58+/-15 to 37+/-23). CONCLUSION: Although this was not a double-blind, prospective, randomised study, the strong improvement noticed in the half-dose group suggests that etanercept 25 mg once a week can induce major clinical and biological relief in some patients with RA or spondylarthropathy. PMID- 17337352 TI - Suggestions for managing pyogenic (non-tuberculous) discitis in adults. AB - OBJECTIVES: To develop recommendations about identifying the causative organism, obtaining imaging studies, and selecting pharmacological and non-pharmacological treatments in adults with pyogenic discitis and vertebral osteomyelitis (PDVO). METHODS: A rheumatologist and an infectiologist drafted recommendations based on their personal experience and a review of studies in English or French retrieved on Medline using the following search terms: "infectious spondylodiscitis", "infectious spondylitis", "spondylodiscitis", "discitis", "vertebral osteomyelitis", "spine infection", and "bone and joint infections". The recommendations were submitted to four experts for validation. RESULTS: 85 articles were selected for detailed review. No prospective randomized controlled trials were identified. Antimicrobial therapy should be initiated only after recovery of the causative organism in blood cultures or percutaneous disk biopsy specimens, except in patients with neutropenia or severe sepsis. The initial treatment rests on a combination of two bactericidal and synergistic antimicrobials in high dosages. The total duration of antimicrobial therapy should be 12 weeks at least. Radiographs of the spine and chest and magnetic resonance imaging (MRI) of the spine should be performed routinely during the initial evaluation. In PDVO due to hematogenous dissemination of a streptococcus or staphylococcus, routine echocardiography may be in order. Radiographs centered on the affected disk should be obtained 1 and 3 months into antimicrobial therapy and 3 months after treatment discontinuation. Follow-up MRI is usually unnecessary when the clinical and laboratory abnormalities respond to treatment. If not, or if the initial investigations show a collected abscess, a repeat MRI after 1 month of antimicrobial treatment may be useful. Clinical and laboratory follow-up is mandatory throughout antimicrobial therapy and during the first 6 months after treatment discontinuation. CONCLUSIONS: Recommendations based on descriptive studies and expert opinion were developed. They can be expected to improve the quality and uniformity of PDVO management. Further studies are needed to improve the level of evidence that is available for developing recommendations. In particular, prospective randomized multicenter studies should be performed to compare the intravenous to the oral route for initial antimicrobials administration and to compare different treatment durations. PMID- 17337353 TI - [Laparoscopic management of occult cervical cancer discovered after simple hysterectomy]. AB - OBJECTIVES: To assess the feasibility and morbidity of surgical management by combined laparoscopic and vaginal approach after cervical cancer diagnosed at the time of simple hysterectomy. PATIENTS AND METHODS: From 2000 to 2005, 10 patients were referred with occult cervical cancer discovered after simple hysterectomy. All these patients had laparoscopy for surgical staging. RESULTS: Eight on ten patients had complete laparoscopic staging: pelvic lymphadenectomy (N=8), radical colpectomy (N=5). Operative time, pelvic lymph nodes resected, postoperative stay were respectively 261.3 minutes (200-400), 27 (23-38), 4.4 days. There were 2 symptomatic lymphocysts. Pelvic lymph nodes were positive for 1 patient with negative paraaortic nodes. Residual disease was present in 2 cases: 1 parametrial and vaginal involvement, 1 ovarian metastasis. 5 patients had adjuvant treatment: 2 combined pelvic external radiotherapy and brachytherapy, 1 pelvic external radiotherapy, 1 pelvic concurrent chemoradiation and 1 brachytherapy only. Two on ten patients needed a laparoconversion, one for ovarian involvement and one for technical failure. With a median follow-up of 29.7 months (4-63), 3 patients recurred. 3 patients recurred above 5 patients with pelvic lymphadenectomy but without parametrectomy versus no recurrence above 5 patients with pelvic lymphadenectomy and parametrectomy. DISCUSSION AND CONCLUSION: Surgical staging of occult cervical cancer discovered after simple hysterectomy is necessary for indication of adjuvant treatment. Laparoscopy combined with vaginal surgery is feasible and safe, inducing fewer adhesions which is important for adjuvant radiotherapy. The realization of a radical parametrectomy seems to offer a local control of the disease and a decrease in the risk of recurrence, which need to be confirmed by conducting a study with more patients. This emphasize the necessity of creating a national record to register all women managed for occult cervical cancer. PMID- 17337354 TI - A study on electron impact mass spectrometry of epoxy methylated fullerenols. AB - Mass spectra of the epoxy methylated[60]fullerenols were obtained by EI mass spectrometry using "desorption" or "in-beam" technique. The mass spectra have an intense molecular monocation peak M(+) and a weak dication peak M(++), revealing the stability of these products under the MS (EI) conditions. The remaining peaks correspond to the successive loss of methyl groups and oxygen atoms for which the pure fullerene represents a more stable product. The distinction between the multiply charged fullerene C(60)(z+) and their fragments with equal m/z was also studied. PMID- 17337355 TI - Background levels of key biomarkers of chemical exposure within the UK general population--pilot study. AB - The use of biomarkers is now an accepted measure of chemical uptake (possibly exposure) in risk assessment. However, information on background exposures and biomarker concentrations of many environmental chemicals in the general UK population is limited. This study aims to determine reference ranges for eleven biomarkers of chemical exposure, measurable in urine, within the general adult UK population. The study will involve 400 volunteers throughout the UK and is currently underway. Described here is a pilot study, carried out during August and September 2005 to test the study methodology. The initial results of the postal survey and urinary concentrations for cadmium (UCd) and mercury (UHg) are reported. A total of 78 individuals were recruited by post from the UK Electoral Register, to take part in the pilot study. Participants were asked to complete a questionnaire and provide a urine sample. The overall response rate was 16%, of which 60.3% were female and 39.7% male. Those living in suburban areas accounted for 60% of respondents, current smokers 12.8% and vegetarians 1.3%. Levels of UCd were higher in females compared to males and smoking status influenced levels; smokers displayed higher levels of UCd than individuals who had previously smoked or who had never smoked. The mean, median and range of UHg was 1.12, 0.55 (24 hours after operation) and SS group had a short hospital stay. A total of 18 variables, including five patient variables, nine operative variables and four postoperative variables, were identified for univariate analysis. Significant pre- and postoperative factors were included in the multivariate analysis to identify independent predictive factors for long hospital stay. RESULTS: Of the 278 patients, 118 (44.2%) could be discharged within 24 hours, while 149 (55.8%) had long hospital stay. Nine significant factors were identified in the univariate analysis; three independent factors were found to predict long hospital stay in the multivariate analysis. Patients with age more than 60 years had double risk of long hospital stay. Patients who could not tolerate diet within 8 hours or took more than two tablets of oral analgesia (dologesics) had a four- and threefold increase in risk of long hospital stay, respectively. CONCLUSION: With careful patient selection, optimal postoperative pain control and early resumption of diet with better management of postoperative nausea and vomiting, ambulatory LC was feasible and safe. PMID- 17337368 TI - Stapled haemorrhoidopexy for prolapsed haemorrhoids: short- and long-term experience. AB - OBJECTIVE: In prolapsed haemorrhoids, there is a permanent outward displacement of the mucosa of the anal canal, often involving the rectal mucosa. On this background, Longo set up a technique in 1998 to reduce haemorrhoidal prolapse, using a circular stapler. The aim of this study is to report our 7 years of experience on patients treated using this new surgical technique for haemorrhoids. METHODS: Between October 1998 and June 2005, 496 patients were treated by stapled haemorrhoidopexy. We analysed data from 300 of these patients in whom follow-up was longer than 12 months. RESULTS: The duration of the procedure ranged from 12 to 45 minutes. In 184 patients (37%), haemostatic stitches of the suture line were necessary after firing the stapler. Pain score (visual analogue scale, 1-10) after 24 hours ranged from 2 to 4 and after 5 days from 1 to 3. The average length of hospital stay was 2.3 days. Long-term results showed that only 9% of patients required further treatment after long follow-up, while 10.1% complained of some discomfort or residual symptoms in the perianal region. CONCLUSION: Our short- and long-term results show that stapled haemorrhoidopexy for haemorrhoids is a safe procedure with less pain and lower complication rate compared to conventional haemorrhoidectomy. PMID- 17337369 TI - Preemptive ropivacaine local anaesthetic infiltration versus postoperative ropivacaine wound infiltration in mastectomy: postoperative pain and drain outputs. AB - OBJECTIVE: The aim of this study was to investigate if preemptive local infiltration (PLA) with ropivacaine could improve postoperative pain and determine its effect on drain output postmastectomy with axillary dissection. METHODS: This was a prospective, randomized trial comprising 30 women allocated to two groups: one to receive postoperative wound infiltration (POW) of 20 mL of 0.2% (40 mg) ropivacaine (Naropin) versus PLA with 20 mL of 0.2% ropivacaine (Naropin) diluted with 80 mL of 0.9% saline, total volume 100 mL. A visual analogue scale (0-100 mm) and angle of shoulder abduction were used for evaluation of pain. Postoperatively, all patients received oral ibuprofen 400 mg tds. RESULTS: There was no significant difference in postoperative pain for the first 3 days between the two groups. There were wider shoulder abduction angles in the 1st and 3rd postoperative days in the PLA group, but this was not significant. Operative time was significantly shorter in the PLA group than in the POW group (69.34+/-59.37 minutes vs. 109.67+/-26.96 minutes; p=0.02). The axillary drain was removed earlier in the preemptive group, 5.4+/-1.55 days versus 6.8+/-2.04 days in the postoperative group (p=0.04). CONCLUSION: We found no difference in postoperative pain between preemptive tumescent ropivacaine infiltration and postoperative ropivacaine wound infiltration. PMID- 17337370 TI - Aspiration of breast abscess under ultrasound guidance: outcome obtained and factors affecting success. AB - OBJECTIVE: To assess ultrasonographically (US) guided needle aspiration of breast abscesses as an alternative to surgical incision and drainage. METHODS: In our prospective study, 30 patients with 31 breast abscesses (one patient had bilateral breast abscess) underwent percutaneous breast abscess drainage under US guidance with local anaesthesia and oral antibiotics between 1 January 2004 and 31 March 2005. These patients consisted of 16 (53.3%) non-lactating and 14 (46.7%) lactating women, with ages ranging from 18 to 68 years (median, 28 years). The racial distribution comprised 26 (86.7%) Malays, three (10%) Chinese and one (3.3%) Indian. All patients had the chief complaint of breast swelling and 25 (83.3%) had breast pain. Clinically, 28 (93.3%) were found to have a palpable mass. Nine (30%) lesions were in the upper outer quadrant of the left breast. US diameters ranged from 1 to 15 cm (median, 4 cm). The pus volumes varied from 1 to 200 mL (median, 14 mL). RESULTS: Fifteen (50%) patients required only a single aspiration, 10 required multiple aspirations and five required incision and drainage. Those patients in whom needle aspiration failed had multiloculated lesions irrespective of abscess volume and size. CONCLUSION: Needle aspiration with ultrasound guidance is an effective treatment for breast abscess irrespective of abscess volume and size. PMID- 17337371 TI - Role of helical nonenhanced computed tomography in the evaluation of acute flank pain. AB - OBJECTIVE: To evaluate the role of helical nonenhanced computed tomography (NECT) in the diagnosis of acute flank pain. METHODS: Seventy-five consecutive patients were analysed retrospectively for profile, loin pain, urine analysis and NECT findings. Diagnostic accuracy of NECT for urolithiaisis was calculated. The value of combined microhaematuria and NECT in the diagnosis of flank pain was also highlighted. The potential for identifying phleboliths and alternative diagnoses on NECT was also explored. RESULTS: There were 46 males and 29 females with an average age of 42.2 years. Forty-four patients presented with acute left flank pain. NECT carries a sensitivity and specificity of 96% for the diagnosis of stone disease. Combined with microhaematuria, NECT has 100% accuracy in picking up urinary tract stones. CONCLUSION: NECT is the first imaging investigation of choice for the evaluation of patients presenting to the emergency department with flank pain and suspected renal colic. PMID- 17337372 TI - Laparoscopic adrenalectomy is feasible for large adrenal masses>6 cm. AB - OBJECTIVE: Laparoscopic adrenalectomy (LA) has become the established procedure for adrenal masses less than 6 cm. The role of LA for large adrenal masses is well defined to a lesser extent. METHODS: Thirty-six LAs were performed in 32 patients (including four patients with single stage bilateral adrenalectomies) over a period of 3 years, from May 2002 to 2005. Patients were divided into two groups based on the tumour size, i.e. masses less than 6 cm (group I) and masses 6 cm or more (group II).The results with respect to mean (95% confidence interval) operative time, blood loss, postoperative course and complications were compared. RESULTS: Group II included 11 LAs performed in 10 patients including one bilateral LA for bilateral phaeochromocytomas in multiple endocrine neoplasia 2A. The mean size (+/-standard deviation) of masses was 8 cm (+/-1.47). In comparison, 22 patients in group I underwent 25 adrenalectomies (including three bilateral single stage procedures for Cushing's syndrome). The mean size of masses was 4.1 cm (+/-1.27). There were eight and six phaeochromocytomas in groups I and II, respectively. By comparing groups I and II, only minimal increase in blood loss and operating time was noted with no significant difference in hospital stay and morbidity. Two cases required conversion to hand assistance towards the end of the procedure in view of their large size. CONCLUSION: LA is the procedure of choice for small adrenal masses but is also feasible for large functioning and nonfunctioning adrenal masses with equally good results. Even bilateral large functioning tumours can be treated safely by LA in a single stage when sufficient experience with the procedure is attained. PMID- 17337373 TI - Epithelial migration in open mastoidectomy cavities. AB - OBJECTIVE: To study the rate and pattern of epithelial migration in 18 dry, open mastoidectomy cavities. METHODS: This was a prospective study of 19 patients who had undergone mastoidectomy at a secondary (state) hospital and a tertiary referral centre at least 6 months previously and whose mastoid cavities were dry and not infected. Their mastoidectomy cavities were cleaned and India ink dots applied in its medial aspect under microscope. The patients were followed up at 1 or 2 weekly intervals for a minimum of 3 months or until the dots disappeared, whichever came first. On follow-up, the cavities were examined under microscope. If migration was observed, the rate and pattern were noted. RESULTS: Most (94.4%) of the cavities were noted to have epithelial migration laterally. No migration was observed in 5.6%. The start of migration of ink dots was noted in the 2nd week in 53% of the cavities, with a mean of 3.05 weeks. The mean rate of migration was 0.68 mm/week. CONCLUSION: Epithelial migration appears to be predominantly lateral (94.4%), with onset in the 2nd week (53%) at a rate of 0.68 mm/week. Epithelial migration might not play an important role in accumulation of wax in open mastoidectomy cavities. PMID- 17337374 TI - Working hours of surgical residence: perspective of a group of surgeons in a regional hospital in Hong Kong. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education and European working time directive have restricted residents' workweek to 80 and 48 hours, respectively. Impacts on resident's training and health services are under evaluation in western countries. However, relevant studies are deficient in Hong Kong. METHODS: Surgeons in a regional hospital of Hong Kong were recruited. Opinions were collected by semi-structured questionnaire. RESULTS: Response rate was 82%. Most respondents agreed that residents' work hours should be limited. Seventy-two percent thought that the addition of physician assistants, nurse practitioners and ancillary staff could help decrease the workload of residents. More than 60% thought that residents should have post-call afternoon off. Seventy two percent worried that the number of operations residents performed would decrease. Only half agreed that long work hours was part of resident training and 56.3% agreed that the training period should be lengthened because of limiting work hours. Ninety-four percent agreed that sleep-deprived residents would create more medical errors; 72% thought that long work hours would impair quality of care. Surprisingly, only 28% thought that limiting work hours would compromise continued patient care. CONCLUSION: Most respondents opine that resident work hours should be regulated and welcome minor rescheduling of residents' workflow. The impacts on residents' training and patient care require further evaluation. PMID- 17337375 TI - Chronic gastric anisakiasis presenting as pneumoperitoneum. AB - Typically, the diagnosis of gastric anisakiasis is made at endoscopy with the identification of anisakis larvae. We report a case of gastric anisakiasis presenting as pneumoperitoneum. A 70-year-old Japanese woman was admitted to our hospital with abdominal fullness and pain. Plain chest X-ray in the upright position showed the presence of free gas below the diaphragm. A tentative diagnosis of perforation peritonitis was made and an emergency laparotomy was performed. At laparotomy, a 4 cm, circumscribed red mass was noted on the anterior wall of the upper body of the stomach near the lesser curvature and a partial gastrectomy was carried out. The histological diagnosis showed a foreign body, assumed to be a part of anisakis larvae, seen in the centre of the granuloma. On the serosal aspect, there was histological evidence of peritonitis with fibrin and neutrophils. In addition, an antianisakis larvae immunoglobulin G antibody test was positive. Chronic gastric anisakiasis was suspected because of the presence of eosinophilic granuloma in the resected area and denatured anisakis larvae. Thus, we interpret this case as gastric perforation acutely based on chronic gastric anisakiasis. PMID- 17337376 TI - Rectal stump lavage: simple procedure resulting in life-threatening complication. AB - In colorectal resections, rectal stump lavage is commonly performed prior to primary anastomosis for reducing bacterial counts and minimizing the risk of anastomotic recurrence. Being a potent bactericidal and cytotoxic disinfectant, chlorhexidine is frequently chosen as the irrigation solution of choice for such purposes. Despite its widespread use, the potential for developing chlorhexidine allergy is still a major concern due to the ever-rising number of literature reports of hypersensitivity reactions to chlorhexidine in surgical patients. This report illustrates the first reported case of life-threatening chlorhexidine anaphylaxis after its use in rectal stump lavage for colorectal resection. This report serves as a reminder of the potential danger of this "hidden allergen" in clinical practice. PMID- 17337377 TI - Malignant paraganglioma of the retroperitoneum with lung metastases: a 13-year survivor after radical surgery. AB - We present a 23-year-old patient with extra-adrenal retroperitoneal paraganglioma with lung metastases who was successfully treated by complete removal of the tumour. Lung metastases were the first manifestation of the disease, and an abdominal computed tomography scan showed a large mass in the retroperitoneum with marked contrast enhancement. Angiography demonstrated a hypervascular mass with many feeding arteries, but vascular invasion was not apparent. The retroperitoneal tumour was resected completely followed by resection of lung metastases after 1 month of observation. The patient was disease free for 13 years after this radical surgery. The survival rate in patients with retroperitoneal paraganglioma with lung metastasis is low, and this case represents the longest surviving period reported in the literature. These tumours are usually large and located in the para-aortic region, and hence resection is sometimes challenging. We believe that a complete and meticulous surgical procedure is a prerequisite for long survival from this rare disease. PMID- 17337378 TI - Acute anuric renal failure following jering bean ingestion. AB - Djenkol beans or jering (Pithecellobium jeringa) is a traditional delicacy consumed by the local population in Malaysia. Jering poisoning or djenkolism is characterized by spasmodic pain, urinary obstruction and acute renal failure. The underlying pathology is an obstructive nephropathy, which is usually responsive to aggressive hydration and diuretic therapy. We present a case of djenkolism following ingestion of jering. The patient required urgent bilateral ureteric stenting following the failure of conservative therapy. Healthcare providers need to recognize djenkolism as a cause of acute renal failure and the public educated on this potential health hazard. PMID- 17337379 TI - Transplantation of crossed fused renal ectopia. AB - Crossed fused renal ectopia is a type of congenital fused anomaly of the kidney. This type of kidney, when encountered, can be used as a donor organ to provide useful solution to the critical shortage of available organs for transplantation. PMID- 17337380 TI - Seminoma in a male phenotype 46XX true hermaphrodite. AB - Although true hermaphrodite is uncommon, it has been reported in more than 400 individuals. Tumours arising in the gonads of true hermaphrodite is a very rare finding and only very few cases have been reported in the literature. We report a case of a 35-year-old phenotype man with bilateral undescended testis with lump hypogastrium. On examination, he had an ovotestis on one side and pure seminoma arising in testis on the other side. The seminoma arising in the left undescended testis was successfully treated by excision and combination chemotherapy. Cytogenetic studies revealed that 46XX karyotype with primer specific for the sex determining region of the Y chromosome was negative. The karyotypic abnormality noticed in the patient is also reviewed in the article. PMID- 17337381 TI - Tracheal papilloma with exceptionally longer interval of recurrence. AB - A case of recurrent respiratory papilloma of the trachea was reviewed in accordance with other literature. A 66-year-old man with the chief complaint of haemoptysis was referred to our department for meticulous checkup. According to his past medical history of laser ablation for laryngeal and tracheal papilloma, recurrence of the papilloma was first suspected and confirmed by bronchoscopic biopsy. The recurrent papilloma, of about 5 mm in diameter, was located at the same endotracheal lesion, left side of the middle trachea, where the former first and second tracheal papillomas had been detected and treated with Nd-YAG laser. Under general anaesthesia with endotracheal intubation, the patient underwent bronchoscopic resection of the recurrent papilloma with KTP laser. The bronchoscopic resection was uneventful, as was the postoperative course. In this report, the clinical manifestations of and therapeutic approach for tracheal papilloma are reviewed. PMID- 17337382 TI - [Role of PPARgamma in the control of prostate cancer growth: a new approach for therapy]. AB - In several cases of prostate cancer, resistance to hormonal therapies is observed. Alternative therapeutic strategies for the treatment of prostate cancer are of great interest. Participation of the nuclear receptor PPARgamma in the physiopathology of the prostate, in particular in prostate cancer has been recently studied. PPARgamma is a member of the hormone nuclear receptor superfamily. As for most members of the family, its activity is regulated by ligands. PPARgamma has been shown to be over-expressed in several cancers, including prostate cancer. In vitro and in vivo studies have demonstrated anti proliferative and pro-apoptotic actions of the PPARgamma agonists thiazolidinediones, suggesting that PPARgamma could be a promising therapeutical target for the treatment of cancer. No effects of PPARgamma agonists have been observed, however, in a large randomized clinical trial in the "rising PSA" group of prostate cancer patients. This suggests that PPARgamma activity is controled by other factors, in addition to its ligands, in prostate cancer. We have shown that PPARgamma activity is repressed by HDACs. Moreover, PPARgamma activity is enhanced in the presence of HDAC inhibitors. A combination treatment using HDAC inhibitors and PPARgamma agonists results in growth arrest of prostate tumors in mice. Furthermore, the combination therapy inhibits invasion of prostate cancer cells in vivo, through upregulation of the expression of the E-cadherin gene. PMID- 17337383 TI - [Utility of MRI contrast agents for diagnosis and treatment follow-up in cancer]. AB - Numerous and diverse contrast agents are available in MRI. Their use is focused on two directions : microcirculation imaging and cell capture imaging. Microcirculation imaging uses gadolinium chelates and technical advances in MRI. It quantifies perfusion and capillary permeability applying a physiological analysis to the tissue enhancement curve. Cellular imaging uses labeled cells as contrast agents ; the cells can be labeled in vitro or in vivo. The roles of imaging in cancer are numerous. For diagnosis, detection is improved, particularly for liver metastases with the development of cellular imaging and liver-specific contrast agents. Cellular imaging opens promising perspectives for cellular therapy. Microcirculation imaging characterizes tumors more specifically, particularly in breast imaging. Regarding treatment follow-up, the impact of imaging is considerable. Microcirculation imaging predicts treatment response even before initiation of therapy. During treatment, it allows a more complete evaluation taking into account physiological parameters, better adapted to monitor therapies currently in development, such as anti-angiogenic drugs. Therapeutic effects can be detected earlier, before morphological changes. Cellular imaging offers new prospects to monitor cellular therapy. The use of MRI contrast agents is moving towards the coupling of functional to morphological analysis. This constitutes a new approach perfectly adapted to diagnosis and therapy follow-up in oncology. PMID- 17337384 TI - [Vascular interventional procedures in oncology]. AB - Indications for interventional radiology have increased, and various arterial and venous procedures are nowadays possible in oncology. Besides emergency procedures, scheduled palliative or curative procedures require multidisciplinary cooperation emphasizing on cautions related to iodine contrast media and concerning immunosuppresion, hemostasis disorders, analgesia, and the choice of the adequate approach. Diagnostic endovascular biopsies and venous sampling may be performed. Embolisation procedures are useful for achieving hemostasis, tumor devascularisation, or chemo-embolisation. Revascularisation procedures concern central vein obstructions, catheter occlusion or arterial stenoses and occlusions. Vena cava filtering, retrieval of intravascular foreign bodies and percutaneous implantation of ports can also be indicated, as well other treatments of central venous access complications. The principles, technical aspects, results, and indications of these various endovascular procedures are described in this review. PMID- 17337385 TI - [Interventional radiology in bone metastases]. AB - Interventional radiology takes a large place in the treatment of bone metastases by numerous techniques, percutaneous or endovascular. Vertebroplasty appears actually as the most important technique for stabilisation of spine metastases as it induces satisfactory stabilisation of the vertebra and offer clear improvement of the quality of life. Due to the success of this technique cementoplasty of other bones, mainly pelvic girdle, largely develop. The heath due to the polymerisation of the cement induce carcinolytic effect but this effect is not as important as that can be created with radiofrequency destruction. This last technique appears actually as the most important development to destroy definitively some bone metastases and replace progressively alcoholic destruction of such lesions. Angiographic techniques appear more confidential but endovascular embolization is very useful to diminish the risk of surgical treatment of hyper vascular metastases. Chemoembolization is actually developped to associate the relief of pain induced by endovascular embolization and the carcinolytic effect obtained by local endovascular chemotherapy. All these techniques should develop largely during the next years and their efficacy and safety should improve largely by treating earlier the metastasis. PMID- 17337386 TI - [Measurement of tumour response to cancer treatment: morphologic imaging role]. AB - New forms of cancer chemotherapy are tested in therapeutic trials (phase I, phase II or phase III) while chemotherapeutic agents whose efficacy has already been demonstrated are used, in routine clinical practice, in the context of protocols. The overall survival rate is the best objective parameter of efficacy of the treatments tested, but this parameter is obtained too late, as the effect on the tumour must be determined as soon as possible in order to institute another treatment if necessary. Tumour response, or objective response, is based on changes in the number and size of measurable primary or secondary tumour "targets". These parameters are obtained more rapidly than survival data, but their reliability is highly dependent on the quality of comparative clinical and especially radiological measurements of tumour targets. Medical imaging plays an essential role in these assessments. The absence of standardized techniques, poor selection of targets and inaccurate measurements can bias the results, particularly those of therapeutic trials. In view of the economic, scientific and patient-related stakes involved, a very rigorous approach is essential, directly implicating the responsibility of radiologists performing assessment examinations. The World Health Organization (WHO) guidelines defining the method of measurement of solid tumours and response criteria are no longer adapted to technical progress in imaging. Recently these guidelines have been updated and a new set of criteria has been proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Group, taking into account progress in imaging. They remain based on measurement of the size of the target lesion. The use of this single criterion of size to evaluate response to treatment needs to be discussed in the light of new technologies able to provide information on tumour composition, metabolism or neovascularization, modifications of which reflect response to treatment before a reduction in tumour volume can be detected. PMID- 17337387 TI - [From cytogenetics to cytogenomics of dermatofibrosarcoma protuberans family of tumors]. AB - Dermatofibrosarcoma protuberans (DP) is a rare, slow growing dermal neoplasm of intermediate malignancy. It is made of spindle-shaped tumor cells in a storiform pattern often positive for CD34. The preferred treatment for DP is a surgical wide excision with pathologically sane margins of 3 cm. At the cytogenetic level, DP cells are characterized by either supernumerary ring chromosomes composed of sequences derived from chromosomes 17 and 22 or more rarely of translocations t(17;22). Rings have been mainly observed in adults whereas translocations have been reported in all pediatric cases. These chromosomal rearrangements lead to the formation of a specific fusion gene : COL1A1-PDGFB detected in rings as well as in translocations. DP is therefore a unique example of tumor in which the same molecular event occurs either on rings or linear translocation derivatives and the chromosomal abnormalities display an age-related pattern. So far, the COL1A1 PDGFB fusion gene remains the only fusion gene identified in this tumor. It is also present in variant forms of DP such as giant cell fibroblastoma, Bednar tumor, adult superficial fibrosarcoma and the granular cell variant of DP demonstrating that these tumors are not distinct entities but morphological variants of DP. The breakpoint localization in PDGFB was found to be remarkably constant, placing exon 2 of PDGFB under the control of the COL1A1 promoter. In contrast, the COL1A1 breakpoint was found to be variably located within the exons of the alpha-helical coding region (exons 7-47). No correlation between the breakpoint location in COL1A1 and the age of the patient or any clinical or histological particularity has been established. Moreover, no preferential breakpoint appears to be more particularly linked to one or another variant of DP. The COL1A1-PDGFB fusion gene is detectable either by multiplex RT-PCR with a combination of forward primers designed from a variety of COL1A1 exons and one reverse primer for PDGFB exon 2, or by in situ fluorescence hybridization (FISH) on interphase nuclei from frozen or fixed paraffin-embbeded sections. The COL1A1 PDGFB fusion gene is not found in approximately 8% of DP cases, suggesting that genes other than COL1A1 or PDGFB might be involved in a small subset of cases. It has been proposed that PDGFB acts as a mitogen in DP cells by autocrine stimulation of the PDGF receptor. The PDGF receptor tyrosine kinase antagonist imatinib mesylate has recently been used in clinical trials; its efficiency has been demonstrated in several cases, which allows it to be considered as a novel treatment strategy for metastatic or locally advanced DP. PMID- 17337388 TI - [Aberrant methylation of tumor suppressor genes in head and neck squamous cell carcinoma: is it clinically relevant?]. AB - During malignant transformation, the malignant cell accumulates epigenetic abnormalities that do not alter the DNA sequence but are transmissible during divisions and modify genes expression. The methylation of CpG islands in the tumor suppressor genes (TS genes) promoters inhibits their transcription ; it is a mecanism of gene inactivation as frequent as allelic deletions. The methylation profile (or panel of methylated genes in a tumor), similarly to allelic deletions, varies with the tumor histology. Within head and neck squamous cell carcinoma (oral cavity, larynx and oropharynx), 19 genes have been analysed, among them 5 are frequently methylated, i.e. : p16, ECAD, DAPK, MGMT et TIMP3. The method of methylation analysis, based on a bisulfite treatment followed by a PCR amplification, is sensitive and specific enough to allow the detection of abnormalities in biological fluid that drain the tumor or in circulating tumoral DNA. In the head and neck squamous cell carcinoma, correlation between the methylation profile in tumor and paired saliva is excellent ; thus methylation analysis in saliva is a very promising approach for early cancer detection in high risk patients or for the post treatment follow up and rapid diagnosis of relapse. The methylation signature might also reflect the tumor prognosis and complete the histology to define the diagnosis. Finally, DNA methylation is reversible with demethylating agents, a new avenue for cancer therapy in association with conventional chemotherapy. PMID- 17337389 TI - [Rituximab: mechanism of action and resistance]. AB - Rituximab is now routinely use in clinical practice for B cell lymphoma and chronic lymphocytic leukaemia treatment. Mechanisms of action of this monoclonal antibody are not fully understood. Antibody dependent cellular cytotoxicity (ADCC), complement dependent toxicity (CDC) and apoptosis have been all shown to play a role. But the prominence of each mechanism is considerably varying among the different reports, the studied cell lines and the experimental models. A lack of explanations still exists between the efficacy observed in vivo and the low reproducible cytotoxicity reproduced shown in vitro. Despite an intensive research, most of the mechanisms of resistance to rituximab are unknown. PMID- 17337390 TI - [Invasive cervical cancer treatment costs in France]. AB - The objective of this study was to estimate the direct costs of invasive cervical cancer (ICC) management to the French national health insurance system the 1st year after ICC diagnosis. A retrospective survey was conducted in three centres in 2005, including 42 patients admitted for ICC between 2001-2003. Medical records were examined for data relating to treatments and to determine the management costs. To estimate the annual cost of ICC management in France, data were extrapolated to the general population. The number of new ICC cases in France was estimated at 3,247 in 2003. The mean hospitalisation cost increased with ICC severity at diagnosis: 9,164 euros for stage I, 15,999 euros for stage II, 22,697 euros for stage III, and 26,886 euros for stage IV. The annual cost associated with the medical management of ICC patients was estimated at 43,862,125 euros (sensitivity range 32,973,461 euros-54,748,422 euros) corresponding to a mean patient cost of 13,509 euros. Recent HPV vaccination studies have shown 100 % for a quadrivalent (6,11,16,18) HPV vaccine against HPV induced carcinoma in situ (FIGO stage 0/CIN3), a precursor lesion that may develop into ICC. Thus, it is expected that this vaccine will significantly reduce the socio-economic burden associated with this disease. PMID- 17337391 TI - [Reduction mammoplasty in breast cancers of the lower quadrants]. AB - AIM: Evaluate bilateral reduction mammoplasty in the management of breast cancer in the lower quadrants. PATIENTS AND METHODS: 60 patients were operated on between 1992 and 2003 mean age: 53 years (34-75) by a double team, oncologic and plastic, during the same operative procedure for a cancer in the lower quadrants (T1-2, N0-1a, M0). Radiation therapy was delivered in every patient with a boost in 30% of them. RESULTS: Mean cancer size was 17,5 mm (5-20 m) with 10 N + patients. Mean weight of the lumpectomy was 220 g (80-900!). There was one local recurrence at three years. Cosmetic result was good in 75 % of the patients. Radiation side effects: fibrosis, induration, telangiectasias and vicious cicatrisation on the contro-lateral breast were responsible of the middle quality results. CONCLUSION: Bilateral reduction mammoplasty is a good technique for the management of cancers in the lower quadrants. A double team, with a good logistic organisation, gives a good oncoplastic result. PMID- 17337392 TI - [48th meeting of the American Society for Therapeutic Radiology and Oncology (Astro)]. PMID- 17337393 TI - Immunology of cutaneous leishmaniasis: the role of mast cells, phagocytes and dendritic cells for protective immunity. AB - Millions of Leishmania major infections in humans are reported worldwide. In experimental infections, various phagocytes predominant in skin--neutrophils, macrophages (MPhi) and dendritic cells (DC)--play very distinct roles for the hosts' immune response against L. major infection and they are sequentially engaged via different pathogen recognition receptors as cutaneous leishmaniasis evolves. In the initial "silent" phase without clinically apparent inflammation, L. major promastigotes are primarily phagocytosed by resident MPhi via CR3. Upon activation of cutaneous mast cells, inflammatory neutrophils and monocytes are recruited to the skin coincident with the development of a nodular plaque. Later on, in established infections, DC-, B cell- and T cell-dependent immunity becomes critically important for lesion resolution. Antibody-mediated uptake of L. major by DC leads to IL-12 production and priming of Th1/Tc1 cells, both of which are required for efficient parasite killing by lesional MPhi. Finally, Fc receptor mediated uptake of L. major by MPhi induces counter-regulatory IL-10 production leading to parasite persistence. Thus, the balance between CR3- and FcgammaR triggered anti- and proinflammatory mechanisms involving MPhi and DC is critical for disease outcome. This review highlights the importance of the various phagocytes for the development of anti-Leishmania immunity. PMID- 17337394 TI - Keratins and their associated skin disorders. AB - Keratins are the largest group of intermediate filament proteins that are expressed in the cytoplasm of epithelial cells. They form a cytoskeletal scaffold that maintains cell and tissue integrity and provides vital mechanical support to epithelia. Mutations in 19 different keratin genes have so far been identified as the cause of at least 15 different genetic diseases. Identification of the molecular basis of the keratin disorders has contributed to definite diagnoses and has facilitated genetic counselling. Better understanding of the structure, function and regulatory mechanisms of keratins will be the basis for the development of novel therapeutic approaches to overcome the current treatment limitations. PMID- 17337395 TI - Congenital acantholytic dyskeratotic epidermal naevus following Blaschko's lines versus segmental Darier's disease. AB - A Japanese newborn male with an unremarkable family history presented at birth with verrucous papules on the left side of the trunk and limbs, distributed along Blaschko's lines. Histological examination showed mild acantholytic dyskeratosis, consistent with Darier's disease; however, search for mutations of the SERCA gene, performed on DNA extracted from cells from involved and uninvolved skin and peripheral blood proved negative. The absence of detectable SERCA mutations did not allow confirmation of the diagnosis of (segmental) Darier's disease, and a tentative diagnosis of congenital acantholytic dyskeratotic epidermal nevus was considered. The relationship between the two conditions is briefly discussed. PMID- 17337396 TI - Linear Cowden nevus: a new distinct epidermal nevus. AB - Within the group of epidermal nevi, a so far nameless disorder is described under the term "linear Cowden nevus". This non-organoid epidermal nevus is caused by loss of heterozygosity, occurring at an early developmental stage in an embryo with a germline PTEN mutation, giving rise to Cowden disease. Hence, linear Cowden nevus can be categorized as a characteristic feature of type 2 segmental Cowden disease. Until now, several authors had mistaken this epidermal nevus as a manifestation of Proteus syndrome. The concept of linear Cowden nevus implies that Proteus syndrome is by no means caused by PTEN mutations. As a clinical difference, linear Cowden nevus is markedly papillomatous and thick, whereas linear Proteus nevus tends to be rather flat. Moreover, the spectrum of possibly associated cutaneous or extracutaneous anomalies differs in the two types of nevi. In conclusion, linear Cowden nevus, that may also be called "linear PTEN nevus", represents a distinct clinicogenetic entity. PMID- 17337397 TI - Omenn syndrome: a rare case of neonatal erythroderma. AB - Omenn syndrome is a severe combined immunodeficiency characterized by erythroderma, hepatosplenomegaly, lymphadenopathy and failure to thrive, with activated oligoclonal T lymphocytes and an absence of circulating B cells.A 3 day old boy presented with a congenital erythroderma. Investigations revealed a marked neutropenia and lymphopenia and the absence of a thymus. Genetic studies showed RAG 1 mutations. He was successfully treated with an HLA identical bone marrow transplantation. Omenn syndrome is a rare severe combined immunodeficiency. Most cases are due to mutations in the RAG genes with autosomal recessive transmission. Our observation is original because of an incomplete clinical presentation. During the course of the disease, the child had no failure to thrive, no organomegaly and no recurrent infection. Immunodeficiency must be excluded in every case of neonatal erythroderma and an immunological assessment should be performed without delay. PMID- 17337398 TI - Effect of selenium intake on the prevention of cutaneous epithelial lesions in organ transplant recipients. AB - Organ graft recipients have a high rate of pre-malignant and malignant epithelial lesions. Selenium directly influences the number of Langer-hans cells. In several studies selenium has shown its role in preventing various carcinomas, it was worth investigating whether it could prevent skin cancer linked to human papilloma virus (HPV). A multicentre, randomised, placebo-controlled, parallel group study in 184 recent organ transplant recipients was undertaken. Patients were treated for 3 years with 200 mug/day selenium (91 patients) or a matching placebo (93 patients), and then monitored for 2 years. Occurrence rates of warts and various keratoses (main criterion) and of skin cancers (secondary criterion) were compared in the two groups, using Kaplan-Meyer analyses. There was no difference between the two groups for the main criterion (odds-ratio 1.09, p = 0.72) or the secondary criterion (odds-ratio 3.08; p = 0.15). When both arms were pooled, phenotype and age were not found to be discriminatory factors, whereas a previous history of an actinic keratosis significantly increased the risk of developing a skin cancer by 17.5%. Safety was good and similar in both groups. Selenium was not shown to prevent the occurrence of skin lesions linked to HPV. The occurrence of skin cancer was higher if there had been a previous actinic keratosis, highlighting the importance of early dermatological follow-up of the transplanted population. This was demonstrated by the high rate of epithelial lesions detected, which was more than twice the rate usually reported in the literature. PMID- 17337399 TI - Might there be a link between mannose binding lectin and vitiligo? AB - Mannose binding lectin (MBL) is a calcium dependent lectin that causes predisposition to infections and autoimmune diseases. This study aimed to examine the presence of any association between MBL2 gene variants and vitiligo. Codon 54 (allele B) and codon 57(allele C) polymorphisms in the exon 1 of the MBL2 gene were investigated in samples belonged to 50 healthy controls and 40 patients diagnosed as vitiligo. The PCR-RFLP method was used to investigate the polymorphisms in the MBL2 gene. Codon 57 polymorphism was not detected in any of the subjects from either group. The frequencies of low level MBL2 genotypes for codon 54 (AB and BB) polymorphisms were found to be significantly higher in the patient group compared to controls (37.5% vs. 6%) (p < 0.001). B allele frequency was also significantly higher in the patient group (20%) compared to the control group (3%). These results suggested that codon 54 polymorphism in the MBL2 gene may play a role in susceptibility to vitiligo. PMID- 17337400 TI - Cervical intraepithelial neoplasia associated with epidermodysplasia verruciformis HPV in an HIV-infected patient: a manifestation of immune restoration syndrome. AB - We report a case of a cervical intraepithelial neoplasia associated with epidermodysplasia verruciformis human papillomavirus (HPV) type 5 and HPV type 16 in a human immunodeficiency virus-infected patient. Furthermore, epidermodysplasia verruciformis-like cutaneous eruptions after initiation of highly active antiretroviral therapy has never been described as a manifestation of an immune restoration syndrome. PMID- 17337401 TI - HHV-8 positive Kaposi sarcoma in a patient with end-stage renal disease undergoing hemodialysis: no regressive effect of captopril. AB - Human herpesvirus 8 (HHV-8) has been associated with Kaposi sarcoma (KS) in renal transplant recipients. On the other hand, there are only a few reported cases of KS in patients with end stage renal failure receiving hemodialysis. Here, we report a case of HHV-8 positive, disseminated KS, in a 70-year-old man with renal failure, receiving hemodialysis for 7 months. The KS lesions had begun to develop almost at the same time with the onset of dialysis. The patient had been on captopril therapy since the diagnosis of renal failure. Captopril has been reported to inhibit angiogenesis, and by this way, to reduce tumor growth. However, in our patient, the lesions had developed under the treatment of captopril, and showed no evidence of regression after withdrawal of the drug. PMID- 17337402 TI - Incomplete auriculotemporal nerve syndrome--mimicry of oral allergy syndrome. AB - Pollen allergies are commonly symptomatic as seasonal rhinoconjunctivitis. The majority of patients with pollen allergies develop an oral allergy syndrome due to cross-reactive homologous allergens in plant foods. Symptoms may vary from minor local oropharyngeal sensations and swelling to life threatening angioedema and glottis edema. We present the case of a 6-year-old male with suspected oral allergy syndrome who was referred for allergological work up. However, an incomplete auriculotemporal nerve syndrome was diagnosed, mimicking oral allergy syndrome. PMID- 17337403 TI - Unilateral linear capillaritis: two unusual Chinese cases. AB - Unilateral linear capillaritis (ULC) is a rare special variation of pigmented purpuric dermatosis (PPD), which is characterized clinically by linear or segmental distribution of pigmented purpuric macules located predominantly on the lower extremities and showing a favorable prognosis. In this case report, we describe two unusual cases of ULC, in one male and one female patient, with unilateral lesions involving the upper extremities that loosely follow the dermatome lines. Biopsy results revealed a common histopathology feature to PPD without heavy band-like infiltration in the upper dermis. On review 20 months after the onset, the eruptions of Patient 1 had spontaneously faded from parts of the affected area. Meanwhile, after a period of 18 months post onset, the eruptions of Patient 2 had became less visible after treatment with PUVA for 2 months, leaving a faded pigmentation. PMID- 17337404 TI - Multicentricity of extramammary Paget's disease. PMID- 17337405 TI - Atypical cutaneous herpes virus infection associated with fludarabine chemotherapy of lymphoma. PMID- 17337406 TI - Peripheral T-cell lymphoma masquerading as infectious cellulitis. PMID- 17337407 TI - Primary cutaneous actinomycosis on the nose. PMID- 17337408 TI - Methotrexate-induced toxic epidermal necrolysis-like skin toxicity. PMID- 17337409 TI - Non-traumatic elastofibroma dorsi. PMID- 17337410 TI - Anaphylactic reaction to ranitidine and dexchlorpheniramine. PMID- 17337411 TI - W-type abnormality of the penile raphe. PMID- 17337412 TI - Mild and delayed-onset Proteus syndrome. PMID- 17337413 TI - Norwegian scabies in a healthy woman during oral cyclosporine therapy. PMID- 17337414 TI - Agminated acquired melanocytic nevus on the sole: clinical, dermoscopic and histopathological correlation. PMID- 17337415 TI - Lymphedema of the extremities developed as the initial manifestation of rheumatoid arthritis. PMID- 17337416 TI - Nevus comedonicus with epidermolytic hyperkeratosis. PMID- 17337417 TI - High-tech dermatology. PMID- 17337418 TI - Cosmetic dermatology and skin care. PMID- 17337419 TI - Dermatology and basic science. PMID- 17337420 TI - Entrapment of andrographolide in cross-linked alginate pellets: I. Formulation and evaluation of associated release kinetics. AB - Andrographolide, the 'King of bitters' requires high doses in the form of an extract (33.3%w/w) to be used as a hepatoprotectant. Since a large dose of this herb is known to cause gastric distress, vomiting, loss of appetite and nausea on regurgitation, it was thought of to convert the drug itself into a bitterless micropellet. The technique of ionotropic gelation of sodium alginate with calcium ions with subsequent drug entrapment was employed. The optimization of process parameters like the bore diameter of the needle, % concentration of sodium alginate, method of drying, drying time and temperature, time of contact of the micropellets in calcium chloride solution and concentration of calcium chloride to be used for the gelation were undertaken. The micropellets were finally prepared by adding 2.5%w/v of sodium alginate into a 2%w/v solution of calcium chloride solution using 20-guage flat tip needle and dried using a hot air oven at 60(o)C for 6 hrs. The so formed pellets were completely bitterless and released the andrographolide preferably away from the stomach. Pellets with varied drug: polymer ratio (1:2, 1:1 and 2:1) were prepared accordingly and analyzed for release kinetics. Release studies showed only about 15% release upto 4 hrs in pH 1.2 and pH 4.0 respectively and released the remaining in pH 7.4. The data obtained in the dissolution studies was fitted into various mathematic models defining kinetics of drug release like the zero-order rate equation, first order rate equation, Hixson-crowell, 2/3rd rule, Korsemeyer-Peppas, Baker lonsdale, Higuchi, Weibull, Ford and Hopfenberg Equation. The release kinetics of andrographolide from the alginate pellets was found to be best described by the korsemeyer-peppas equation which provided n values ranging from 1.0-1.47 with good linearity of the best-fit line (R(2)=0.9973). In conclusion, andrographolide can be easily converted to bitterless multiple unit dose oral delivery systems with good entrapment efficiency and a maximum release of 86% by utilizing the technique of ionotropic gelation. PMID- 17337421 TI - Entrapment of andrographolide in cross-linked alginate pellets: II. Physicochemical characterization to study the pelletization of andrographolide. AB - This paper deals with the characterization of pellets containing andrographolide in two parts. The first part deals with characterization of the pellets to ascertain the identity and integrity of andrographolide. Part two involves characterization of the pellets containing Andrographis paniculata extract (33.3%) prepared in the paper I for their micromeritic properties like Particle size, Particle size distribution, Sphericity measurements like Shape ratio and Aspect ratio, Tapped density, Compressibility index, Hausner's ratio and Angle of repose. In addition, our aim was also to derive information about the mechanism of gelation with entrapment of andrographolide to supplement results obtained about the release mechanisms deduced in paper I. Since this work requires use of techniques like FTIR, FTRaman, MTDSC and XRPD, it was necessary to prepare alginate micropellets using pure andrographolide (99.89%) rather than the multicomponent extract using the same procedure discussed in paper I. The integrity of the drug was maintained in the cross-linked micropellets as was seen in the MTDSC and FTIR spectra supported by the FTRaman spectra. The depolymerisation transitions, the reversing and non-reversing heat flow signals were determined using the MTDSC and interpreted to study the mechanism of pelletization. The MTDSC profiles also confirmed the integrity of the drug by exhibiting a sharp endotherm at 232(o)c that is the melting point of andrographolide. The XRPD spectrum of the micropellets ascertained that the crystallinity of andrographolide was maintained. The relationship of the nature of the drug present in the micropellets related to release mechanisms is discussed. In conclusion, it can be said that andrographolide can be successfully incorporated into cross-linked micropellets of alginate without affecting its integrity or nature to deliver it as a bitterless monoherbal preparation. PMID- 17337422 TI - Fatty acid composition of Abies pindrow (West Himalayan fir). AB - The leaves of Abies pindrow, collected from Murree Hills, Punjab (Pakistan) revealed the presence of eleven fatty acids including eight saturated and three unsaturated fatty acids. They ranged from C(14) to C(24) and were detected as methyl esters by GC-MS technique. The saturated fatty acids were present in much greater proportion than unsaturated ones. Isopalmatic acid was found to be major saturated fatty acid and the oleic acid as predominant unsaturated acid. (+)-14 Methyl palmatic acid and (+)-Isosteric acid were the next higher saturated and unsaturated fatty acids respectively. PMID- 17337423 TI - Fosinopril H(2)-receptor antagonists interaction studies by derivative spectroscopy. AB - Fosinopril sodium, a phosphinic acid derivative is an angiotensin converting enzyme (ACE) inhibitor, which had been employed for the treatment of hypertension and congestive heart failure; long tem use of ACE inhibitor often result in stress ulcers due to which H(2) receptor antagonists are also concurrently prescribed. The later compete with histamine for H(2) receptors and block gastric acid secretion and some cardiovascular effects of histamine. Our studies are focused on the in vitro availability of fosinopril in presence of commonly used H(2) receptor antagonists. Derivative spectroscopy has been employed for the quantitation of fosinopril and H(2) receptor antagonists followed by linear regression analysis. These studies were carried out in buffers of pH 7.4 and 9 at 37, 48 and 60( masculine)C. Stability constant and thermodynamic function had also been calculated in order to evaluate the reaction mechanism. Commonly prescribed H(2) receptor antagonists like cimetidine, ranitidine and famotidine were used in these studies. Present study clearly indicated that most of the H(2) receptor antagonists studied decreased the availability of fosinopril which conclude that availability of fosinopril can be affected by the concurrent administration of H(2) receptor antagonists. PMID- 17337424 TI - Isolation of bacillus subtilis MH-4 from soil and its potential of polypeptidic antibiotic production. AB - The genus Bacillus produces mainly polypeptide antibiotics such as bacitracin and polymyxin. Bacillus species were isolated from soil by soil sprinkle technique. And all were screened for the production of antibiotic. Bacillus subtilis MH-4 gave the maximum antimicrobial activity so finally selected for optimization. During optimization of culture conditions for Bacillus subtilis MH-4 best antibacterial activity was obtained at 96 hours of incubation period, at pH-8 and by using glycerol as carbon and L-glutamic acid as nitrogen source. Optimum temperature for antibiotic production was 37 degrees C. The antibiotic was confirmed to be bacitracin by paper chromatography. Antibiotic was further extracted successfully with 1-Butanol, and aqueous concentrate showed activity of 0.8 mg/ml. The antibiotic so produced was found to be narrow spectrum active against only Gram-positive bacteria. PMID- 17337425 TI - Antibacterial activities of Emblica officinalis and Coriandrum sativum against Gram negative urinary pathogens. AB - Present investigation is focused on antibacterial potential of aqueous infusions and aqueous decoctions of Emblica officinalis (amla) and Coriandrum sativum (coriander) against 345 bacterial isolates belonging to 6 different genera of Gram negative bacterial population isolated from urine specimens by employing well diffusion technique. Aqueous infusion and decoction of Emblica officinalis exhibited potent antibacterial activity against Escherichia coli (270), Klebsiella pneumoniae (51), K. ozaenae (3), Proteus mirabilis (5), Pseudomonas aeruginosa (10), Salmonella typhi (1), S. paratyphi A (2), S. paratyphi B (1) and Serratia marcescens (2) but did not show any antibacterial activity against Gram negative urinary pathogens. PMID- 17337426 TI - Neurophysiological role of sildenafil citrate (Viagra) on seminal parameters in diabetic males with and without neuropathy. AB - Sildenafil citrate is a specific inhibitor of phosphodiesterase (PDE) type-5 and represents a powerful therapy for male erectile and fertility dysfunctions of different etiologies. Present study demonstrates whether sildenafil administration modifies seminal parameters in diabetic neuropathic patients. In this investigation 50 insulin dependent (IDDM) and 50 non insulin dependent (NIDDM) diabetic male patients with and without an objective evidence of neuropathy and 50 age matched non diabetic male controls were selected. Every male had age between 20 to 65 years with duration of diabetes distributed over 1 to 20 years. Treatment with 100 mg of oral sildenafil citrate on seminal parameters was evaluated by semen analysis in these patients. In both IDDM and NIDDM diabetic neuropathic patients, chronic sildenafil treatment exhibited a significant decrease in total sperm output and sperm concentration (p<0.001). On the other hand, sperm motility and semen volume were found to be increased by about 40% and 48% respectively in these patients, where as sperm morphology and quality of sperm motility remained unaffected. However both types of non neuropathic diabetics showed a non significant difference in all the above mentioned parameters when compared with the untreated groups and their respective control subjects. A comparison between IDDM and NIDDM neuropathic and non neuropathic diabetic groups further indicated a non significant difference in all the parameters of semen analysis. These findings suggest a chronic neuro physiological effect of sildenafil treatment on male fertility profile exclusively in diabetic neuropathic condition with an improvement in testicular function which was probably arrested due to some kind of testicular hyperplasia resulted by testicular necrosis and promoted spermatogenesis. Sildenafil seems to be associated with an improvement in the entire smooth musculature of reproductive tract and testicular morphology which was altered due to neuropathy like a reduction in excess accumulation of interstitial collagen and calcification in the smooth muscles of seminiferous tubules which made them rigid leading to atonia of bladder and urethra which resulted in partial or retrograde ejaculation associated with a decreased sperm motility. Sildenafil treatment returned back the spermatogenesis to normal with a positive influence on sperm motility and ejaculate volume in these neuropathic patients irrespective of the type of diabetes. PMID- 17337427 TI - In vitro availability of ofloxacin in presence of metals essential to human body. AB - The significance of interaction between ofloxacin and metals ions was evaluated in this study. The absorption of ofloxacin can be negatively affected by concomitant administration of agents containing metal cations. Current studies examine alterations of ofloxacin availability by metal cations and is limited to conventional metal-containing agents such as antacids and mineral supplements. The in vitro availability of ofloxacin was studied in presence of metal ions as magnesium, calcium, chromium, manganese, ferric, ferrous, cobalt, nickel, copper, zinc and cadmium in their salt form in simulated gastric juice, buffers of pH 7.4 and 9 at 37 degrees C by using a modified B.P 2002 dissolution apparatus. UV/VIS (Shimadzu 1601) spectrophotometer was used to analyze the drug by measuring absorbance at 294 nm in simulated gastric juice and at 288 nm in pH 7.4 and 9. The result showed that availability of ofloxacin slightly changed in presence of all metals in all these dissolution mediums. PMID- 17337428 TI - Anti-inflammatory and analgesic effects of Hedychium coronarium Koen. AB - Successive hexane, chloroform and methanol extracts of the rhizome of Hedychium coronarium Koen. (HC) were subjected to evaluate analgesic and anti-inflammatory activities in animal model. In acetic acid-induced writhing test, the chloroform and methanol extract at doses of 400 mg/kg body weight elicited 27.23 and 40.59% inhibition of writhing reflex respectively. Both the chloroform and methanol extracts showed significant elongation of tail flick time (41.15 and 61.32% elongation respectively) at 400 mg/kg body weight. In carrageenan induced rat paw edema test, the chloroform and methanol extracts at a dose of 400 mg/kg body weight showed statistically significant (P<0.01) inhibition of paw edema by 27.46 and 32.48%, respectively at the third hour after carrageenan injection. PMID- 17337429 TI - Effects of repeated restraint stress on serum electrolytes in ethanol-treated and water-treated rats. AB - The present study was designed to evaluate the effects of simultaneous ethanol administration (10%, v/v), and restraint stress (2 hrs/day for 5 day) on serum electrolytes. This restraint stress decreases serum concentration of Na(+), K(+), Ca(2+), phosphorus, and chloride. Ethanol treatment also decreased Na(+), K(+), Ca(2+), phosphorus, and chloride concentration. The decrease in Ca(2+) and phosphorus levels was greater for ethanol-treated restrained than water-treated restrained rats. Ethanol did not affect serum Mg(2+) while it was increased in restrained water-treated rats. Ethanol-treated restrained rats exhibited less serum Mg(2+) than ethanol-treated unrestrained or water-treated restrained rats. Possible mechanism involved in restraint or ethanol-induced changes of electrolytes is discussed. In conclusion, the result of this study suggest that alteration of serum electrolyte caused by repeated restrained in water-treated and ethanol-treated rats could possibly occur due to an increase in sympathetic activity leading to enhanced excretion of these electrolytes. PMID- 17337430 TI - Simultaneous determination of cefazolin or ceftizoxime in presence of ascorbic acid from pharmaceutical formulation and human serum by RP-HPLC. AB - A rapid, sensitive and specific RP-HPLC method involving HPLC-UV detection was developed and validated for simultaneous determination and quantification of cefazoline or ceftizoxime in presence of ascorbic acid. Chromatography was carried out on a pre-packed Kromasil 100, C(18) (5 microm 25 x 0.46 cm) column using acetonitrile: water (60:40; v/v) as mobile phase at a flow rate of 0.75 ml/minute and effluent were monitored at 265 nm for cefazoline and ascorbic acid while at 270 nm for ceftizoxime. The assay was linear over the concentration range of 0.05-100 microg/ml. The method is convenient for determination of cefazoline or ceftizoxime in presence of ascorbic acid with percent recovery ranging from 99.0-100.0% with an inter and intra day CV <3%. The method does not require more than 8 minutes for analysis with good peak resolution and low LOD 0.1 microg/ml and LOQ 0.3 microg/ml. PMID- 17337431 TI - Study of hydroxy propyl guar derivative for its gelling property and it's use in the formulation of tenoxicam gels. AB - Gels of tenoxicam 1% w/w were formulated using 2% w/w hydroxy propyl guar derivative and 3% w/w sodium carboxy methyl cellulose as gelling agents. A detailed rheological investigation was carried out to study the influence of preservative, drug and preservative, solvent system and the preservative, drug, solvent system and the preservative on the pseudoplastic behaviour of polymers. Hydroxy propyl guar derivative in 2% w/w strength resulted in gels with a higher pseudoplastic index value of 3.383 in contrast to an index value of 1.797 for a 3% w/w sodium carboxy methyl cellulose gels of a similar composition. The gels were stored at different temperatures and variations in pH values were recorded. Hydroxy propyl guar derivative based gels revealed variations in pH values over a narrow range in contrast to sodium carboxy methyl cellulose gels. The gels were subjected to short term stability studies by storing gels at refrigerated temperature, lab temperature, at 37 degrees C and at 45 degrees C. Gels based on hydroxy propyl guar derivative revealed better drug keeping qualities in contrast to sodium carboxy methyl cellulose stabilized gels. Release studies of tenoxicam from formulations across hairless albino mice skin revealed a zero order drug release pattern from both the formulations. PMID- 17337432 TI - A comparative study of the effects of hypoglycemic agents on serum electrolytes in the diabetic patients. AB - 30 patients comprised of 3 equal groups which were given 3 types of treatment. Group I given metformin HCl (1+1), maintained a sugar level of 129-340 mg/100 ml. Group II given glibenclamide(1+1), maintained a sugar level of 120-325 mg/100 ml. Group III given a combination of both drugs, maintained a sugar level 112 mg - 46 mg/100 ml. The most suitable of the 3 was the last treatment. Serum electrolytes were measured in all the three groups. Patients taking metformin HCl and glibenclamide showed non significant low sodium with high potassium values respectively. When used in combination, they maintained normal values. On the other hand, serum calcium levels were significantly high in patients taking metformin HCl only; when compared with glibenclamide. However, when both drugs were given to patients, serum calcium remained at normal levels. PMID- 17337433 TI - Comparative effects of single dose and repeated oral tryptophan administration on indoleamine synthesis and memory functions in rats. AB - Brain functions can be affected by the availability of dietary precursors of neurotransmitters. The diet induced increase in tryptophan (TRP) availability has been shown to increase brain serotonin (5-HT, 5-hydroxytryptamine) synthesis and various related behaviors. A prominent role of serotonin in memory functions is widely acknowledged. Increased brain 5-HT concentration is shown to enhance cognitive function whereas decreased 5-HT metabolism in brain has been shown to impair memory. This study was designed to investigate the effects of single dose and repeated TRP administration on brain TRP, 5-HT and its metabolite 5 hydroxyindole acetic acid (5-HIAA) levels and on memory functions in rats. TRP at a dose of 100 mg/kg body weight were orally administered to rats. Assessment of memory in rats was done using the water maze test (WM). Brain TRP, 5-HT and 5 HIAA levels were comparable to control after single TRP administration. Repeated administration of TRP for 6 weeks significantly increased brain TRP (P<0.05), 5 HT (P<0.01) and 5-HIAA (P<0.01) levels with respect to controls. Memory enhancement effect of TRP was not seen after single oral administration whereas repeated TRP intake significantly (P<0.01) enhanced memory functions of rats as evidenced by the decreased latency time to reach the hidden platform in WM. Our results indicate that repeated but not single oral TRP administration is involved in the enhanced memory functions in rats. PMID- 17337434 TI - Probiotics--the friendly bacteria with market potential in global market. AB - With the growing interest in self-care and integrative medicine coupled with our health-embracing increasing population, recognition of the link between diet and health has never been stronger. As a result, the market for functional foods, or foods that promote health beyond providing basic nutrition, is flourishing. Within the functional foods movement is the small but rapidly expanding arena of probiotics - live microbial food supplements that beneficially affect an individual by improving intestinal microbial balance. The consumers' overwhelming interest in and demand for functional foods, including probiotics, make it imperative that health professionals stay abreast of the latest research findings and available products. The global market for functional foods in the coming years is predicted to grow rapidly. Although Japan currently accounts for about one-half of this market, the fastest rate of growth is expected to be in the United States. Probiotic products represent a strong growth area within the functional foods group and intense research efforts are under way to develop dairy products into which probiotic organisms such as Lactobacillus and Bifidobacterium species are incorporated. Such probiotic foods may modulate gut microbial composition, thereby leading to improved gut health, for example, through improved tolerance to lactose in lactose-intolerant individuals or improved resistance to pathogenic bacteria. The fast-growing probiotics market holds a wealth of opportunities, especially for those companies that understand and cater for the final consumer. This monograph provides a summary of research on the health benefits of probiotics and offers information regarding the global market potential of probiotics. PMID- 17337435 TI - The berberis story: Berberis vulgaris in therapeutics. AB - Barberry has played a prominent role in herbal healing for more than 2,500 years. Berberis vulgaris is a common garden bush, native to Europe and the British Isles, naturalized in North America, seems to have history as old as human race. Anthropologists believe in a ritual practice or sacred object, especially by Native Americans that it works as a supernatural power or as preventive or remedy of illness. It is a deciduous shrub having yellow flowers and scarlet colored fruit in the form of berries. Twenty two alkaloids have been reported so far from root, stem leaves and fruit of this plant, which are of medicinal importance. As a herbal remedy it has no match in serving human race since ancient times. It is the most widely used drug in Homeopathic system of medicine for kidney pain and for removal of kidney stones. In this article, we present countless blessings of nature encountered through this herb which are worthy of recording. PMID- 17337436 TI - The genomic HDV ribozyme utilizes a previously unnoticed U-turn motif to accomplish fast site-specific catalysis. AB - The genome of the human hepatitis delta virus (HDV) harbors a self-cleaving catalytic RNA motif, the genomic HDV ribozyme, whose crystal structure shows the dangling nucleotides 5' of the cleavage site projecting away from the catalytic core. This 5'-sequence contains a clinically conserved U-1 that we find to be essential for fast cleavage, as the order of activity follows U-1 > C-1 > A-1 > G 1, with a >25-fold activity loss from U-1 to G-1. Terbium(III) footprinting detects conformations for the P1.1 stem, the cleavage site wobble pair and the A minor motif of the catalytic trefoil turn that depend on the identity of the N-1 base. The most tightly folded catalytic core, resembling that of the reaction product, is found in the U-1 wild-type precursor. Molecular dynamics simulations demonstrate that a U-1 forms the most robust kink around the scissile phosphate, exposing it to the catalytic C75 in a previously unnoticed U-turn motif found also, for example, in the hammerhead ribozyme and tRNAs. Strikingly, we find that the common structural U-turn motif serves distinct functions in the HDV and hammerhead ribozymes. PMID- 17337437 TI - Improving comparability between microarray probe signals by thermodynamic intensity correction. AB - Signals from different oligonucleotide probes against the same target show great variation in intensities. However, detection of differences along a sequence e.g. to reveal intron/exon architecture, transcription boundary as well as simple absent/present calls depends on comparisons between different probes. It is therefore of great interest to correct for the variation between probes. Much of this variation is sequence dependent. We demonstrate that a thermodynamic model for hybridization of either DNA or RNA to a DNA microarray, which takes the sequence-dependent probe affinities into account significantly reduces the signal fluctuation between probes targeting the same gene transcript. For a test set of tightly tiled yeast genes, the model reduces the variance by up to a factor approximately 1/3. As a consequence of this reduction, the model is shown to yield a more accurate determination of transcription start sites for a subset of yeast genes. In another application, we identify present/absent calls for probes hybridized to the sequenced Escherichia coli strain O157:H7 EDL933. The model improves the correct calls from 85 to 95% relative to raw intensity measures. The model thus makes applications which depend on comparisons between probes aimed at different sections of the same target more reliable. PMID- 17337438 TI - Switched alternative splicing of oncogene CoAA during embryonal carcinoma stem cell differentiation. AB - Alternative splicing produces functionally distinct proteins participating in cellular processes including differentiation and development. CoAA is a coactivator that regulates transcription-coupled splicing and its own pre-mRNA transcript is alternatively spliced. We show here that the CoAA gene is embryonically expressed and alternatively spliced in multiple tissues to three splice variants, CoAA, CoAM and CoAR. During retinoic-acid-induced P19 stem cell differentiation, the expression of CoAA undergoes a rapid switch to its dominant negative splice variant CoAM in the cavity of the embryoid body. CoAM functionally inhibits CoAA, and their switched expression up-regulates differentiation marker Sox6. Using a CoAA minigene cassette, we find that the switched alternative splicing of CoAA and CoAM is regulated by the cis-regulating sequence upstream of the CoAA basal promoter. Consistent to this, we show that p54(nrb) and PSF induce CoAM splice variant through the cis-regulating sequence. We have previously shown that the CoAA gene is amplified in human cancers with a recurrent loss of this cis-regulating sequence. These results together suggest that the upstream regulatory sequence contributes to alternative splicing of the CoAA gene during stem cell differentiation, and its selective loss in human cancers potentially deregulates CoAA alternative splicing and alters stem cell differentiation. PMID- 17337439 TI - A synthetic luxCDABE gene cluster optimized for expression in high-GC bacteria. AB - The luxCDABE operon of the bioluminescent bacterium Photorhabdus luminescens has proven to be a superb transcriptional reporter. It encodes a luciferase (LuxA and LuxB) and the enzymes that produce its substrate (LuxC, LuxD and LuxE) so cells that express the cluster emit the 490-nm light spontaneously. The sequence of these genes is AT-rich (>69%) and for this and other reasons, they are not expressed efficiently in high-GC bacteria like Streptomyces coelicolor. We therefore constructed a synthetic luxCDABE operon encoding the P. luminescens Lux proteins optimized for expression in high-GC bacteria. We tested the genes using transcriptional fusions to S. coelicolor promoters having well-established expression profiles during this organism's life cycle. The hrdB gene encodes a housekeeping sigma factor; while ramC is important for the formation of the spore forming cells called aerial hyphae and whiE is required for the production of a grey, spore-associated pigment that is deposited in the walls of developing spores. Using these fusions we demonstrated that our synthetic lux genes are functional in S. coelicolor and that they accurately report complex developmental gene expression patterns. We suggest that this lux operon and our procedure for generating synthetic high-GC genes will be widely useful for research on high-GC bacteria. PMID- 17337440 TI - Structure of native protein C inhibitor provides insight into its multiple functions. AB - Protein C inhibitor (PCI) is a multifunctional serpin with wide ranging protease inhibitory functions, unique cofactor binding activities, and potential non inhibitory functions akin to the hormone-transporting serpins. To gain insight into the molecular mechanisms utilized by PCI we developed a robust expression system in Escherichia coli and solved the crystal structure of PCI in its native state. The five monomers obtained from our two crystal forms provide an NMR-like ensemble revealing regions of inherent flexibility. The reactive center loop (RCL) of PCI is long and highly flexible with no evidence of hinge region incorporation into beta-sheet A, as seen for other heparin-binding serpins. We adapted an extrinsic fluorescence method for determining dissociation constants for heparin and find that the N-terminal tail of PCI and residues adjacent to helix H are not involved in heparin binding. The minimal heparin length capable of tight binding to PCI was determined to be chains of eight monosaccharide units. A large hydrophobic pocket occupied by hydrophobic crystal contacts was found in an analogous position to the hormone-binding site in thyroxine-binding globulin. In conclusion, the data presented here provide important insights into the mechanisms by which PCI exercises its multiple inhibitory and non-inhibitory functions. PMID- 17337441 TI - Members of the heterogeneous nuclear ribonucleoprotein H family activate splicing of an HIV-1 splicing substrate by promoting formation of ATP-dependent spliceosomal complexes. AB - In this study we analyzed members of the heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family to determine their RNA binding specificities and roles in splicing regulation. Our data indicate that hnRNPs H, H', F, 2H9, and GRSF-1 bind the consensus motif DGGGD (where D is U, G, or A) and aggregate in a multimeric complex. We analyzed the role of these proteins in the splicing of a substrate derived from the HIV-1 tat gene and have shown that hnRNP H family members are required for efficient splicing of this substrate. The hnRNP H protein family members activated splicing of the viral substrate by promoting the formation of ATP-dependent spliceosomal complexes. Mutational analysis of six consensus motifs present within the intron of the substrate indicated that only one of these motifs acts as an intronic splicing enhancer. PMID- 17337442 TI - Brain-derived neurotrophic factor regulates the expression and synaptic delivery of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits in hippocampal neurons. AB - Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity in the hippocampus, but the mechanisms involved are not fully understood. The neurotrophin couples synaptic activation to changes in gene expression underlying long term potentiation and short term plasticity. Here we show that BDNF acutely up-regulates GluR1, GluR2, and GluR3 alpha-amino-3-hydroxy 5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits in 7-day in vitro cultured hippocampal neurons. The increase in GluR1 and GluR2 protein levels in developing cultures was impaired by K252a, a tropomyosin-related [corrected] kinase (Trk) inhibitor, and by translation (emetine and anisomycin) and transcription (alpha-amanitine and actinomycin D) inhibitors [corrected] The increase in GluR1 and GluR2 protein levels in developing cultures was impaired by K252a, a Trk inhibitor, and by translation (emetine and anisomycin) and transcription (alpha-amanitine and actinomycin D) inhibitors. Accordingly, BDNF increased the mRNA levels for GluR1 and GluR2 subunits. Biotinylation studies showed that stimulation with BDNF for 30 min selectively increased the amount of GluR1 associated with the plasma membrane, and this effect was abrogated by emetine. Under the same conditions, BDNF induced GluR1 phosphorylation on Ser-831 through activation of protein kinase C and Ca(2+)-calmodulin-dependent protein kinase II. Chelation of endogenous extracellular BDNF with TrkB-IgG selectively decreased GluR1 protein levels in 14-day in vitro cultures of hippocampal neurons. Moreover, BDNF promoted synaptic delivery of homomeric GluR1 AMPA receptors in cultured organotypic slices, by a mechanism independent of NMDA receptor activation. Taken together, the results indicate that BDNF up-regulates the protein levels of AMPA receptor subunits in hippocampal neurons and induces the delivery of AMPA receptors to the synapse. PMID- 17337443 TI - IRAK-4 kinase activity is required for interleukin-1 (IL-1) receptor- and toll like receptor 7-mediated signaling and gene expression. AB - IRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Although regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function is still controversial. To investigate the role of IRAK-4 kinase function in vivo, "knock-in" mice were generated by replacing the wild type IRAK 4 gene with a mutant gene encoding kinase-deficient IRAK-4 protein (IRAK-4 KD). IRAK-4 kinase was rendered inactive by mutating the conserved lysine residues in the ATP pocket essential for coordinating ATP. Analyses of embryonic fibroblasts and macrophages obtained from IRAK-4 KD mice demonstrate lack of cellular responsiveness to stimulation with IL-1beta or a Toll-like receptor 7 (TLR7) agonist. IRAK-4 kinase deficiency prevents the recruitment of IRAK-1 to the IL-1 receptor complex and its subsequent phosphorylation and degradation. IRAK-4 KD cells are severely impaired in NFkappaB, JNK, and p38 activation in response to IL-1beta or TLR7 ligand. As a consequence, IL-1 receptor/TLR7-mediated production of cytokines and chemokines is largely absent in these cells. Additionally, microarray analysis identified IL-1beta response genes and revealed that the induction of IL-1beta-responsive mRNAs is largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in IL-1 receptor (IL-1R)/TLR7-mediated induction of inflammatory responses. PMID- 17337444 TI - Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3 only protein. AB - Bcl-2 family proteins are key regulators of apoptosis and have recently been shown to modulate autophagy. The tumor suppressor Beclin 1 has been proposed to coordinate both apoptosis and autophagy through direct interaction with anti apoptotic family members Bcl-2 and/or Bcl-X(L). However, the molecular basis for this interaction remains enigmatic. Here we report that Beclin 1 contains a conserved BH3 domain, which is both necessary and sufficient for its interaction with Bcl-X(L). We also report the crystal structure of a Beclin BH3 peptide in complex with Bcl-X(L) at 2.5A resolution. Reminiscent of previously determined Bcl-X(L)-BH3 structures, the amphipathic BH3 helix of Beclin 1 bound to a conserved hydrophobic groove of Bcl-X(L). These results define Beclin 1 as a novel BH3-only protein, implying that Beclin 1 may have a direct role in initiating apoptotic signaling. We propose that this putative apoptotic function may be linked to the ability of Beclin 1 to suppress tumor formation in mammals. PMID- 17337445 TI - Human mitochondrial ribosomal protein MRPL12 interacts directly with mitochondrial RNA polymerase to modulate mitochondrial gene expression. AB - The core human mitochondrial transcription machinery comprises a single subunit bacteriophage-related RNA polymerase, POLRMT, the high mobility group box DNA binding protein h-mtTFA/TFAM, and two transcriptional co-activator proteins, h mtTFB1 and h-mtTFB2 that also have rRNA methyltransferase activity. Recapitulation of specific initiation of transcription in vitro can be achieved by a complex of POL-RMT, h-mtTFA, and either h-mtTFB1 or h-mtTFB2. However, the nature of mitochondrial transcription complexes in vivo and the potential involvement of additional proteins in the transcription process in human mitochondria have not been extensively investigated. In Saccharomyces cerevisiae, transcription and translation are physically coupled via the formation of a multiprotein complex nucleated by the binding of Nam1p to the amino-terminal domain of mtRNA polymerase (Rpo41p). This model system paradigm led us to search for proteins that interact with POLRMT to regulate mitochondrial gene expression in humans. Using an affinity capture strategy to identify POL-RMT-binding proteins, we identified mitochondrial ribosomal protein L7/L12 (MRPL12) as a protein in HeLa mitochondrial extracts that interacts specifically with POLRMT in vitro. Purified recombinant MRPL12 binds to POLRMT and stimulates mitochondrial transcription activity in vitro, demonstrating that this interaction is both direct and functional. Finally, from HeLa cells that overexpress FLAG epitope tagged MRPL12, increased steady-state levels of mtDNA-encoded transcripts are observed and MRPL12-POLRMT complexes can be co-immunoprecipitated, providing strong evidence that this interaction enhances mitochondrial transcription or RNA stability in vivo. We speculate that the MRPL12 interaction with POLRMT is likely part of a novel regulatory mechanism that coordinates mitochondrial transcription with translation and/or ribosome biogenesis during human mitochondrial gene expression. PMID- 17337446 TI - Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif. AB - Dbl-related oncoproteins are guanine nucleotide exchange factors specific for Rho family GTPases and typically possess tandem Dbl homology (DH) and pleckstrin homology domains that act in concert to catalyze exchange. Because the ability of many Dbl-family proteins to catalyze exchange is constitutively activated by truncations N-terminal to their DH domains, it has been proposed that the activity of Dbl-family proteins is regulated by auto-inhibition. However, the exact mechanisms of regulation of Dbl-family proteins remain poorly understood. Here we show that the Dbl-family protein, Tim, is auto-inhibited by a short, helical motif immediately N-terminal to its DH domain, which directly occludes the catalytic surface of the DH domain to prevent GTPase activation. Similar to the distantly related Vav isozymes, auto-inhibition of Tim is relieved by truncation, mutation, or phosphorylation of the auto-inhibitory helix. A peptide comprising the helical motif inhibits the exchange activity of Tim in vitro. Furthermore, substitutions within the most highly conserved surface of the DH domain designed to disrupt interactions with the auto-inhibitory helix also activate the exchange process. PMID- 17337448 TI - Functional characterization of cis and trans activity of the Flavivirus NS2B-NS3 protease. AB - Flaviviruses are serious human pathogens for which treatments are generally lacking. The proteolytic maturation of the 375-kDa viral polyprotein is one target for antiviral development. The flavivirus serine protease consists of the N-terminal domain of the multifunctional nonstructural protein 3 (NS3) and an essential 40-residue cofactor (NS2B(40)) within viral protein NS2B. The NS2B-NS3 protease is responsible for all cytoplasmic cleavage events in viral polyprotein maturation. This study describes the first biochemical characterization of flavivirus protease activity using full-length NS3. Recombinant proteases were created by fusion of West Nile virus (WNV) NS2B(40) to full-length WNV NS3. The protease catalyzed two autolytic cleavages. The NS2B/NS3 junction was cleaved before protein purification. A second site at Arg(459) decreasing Gly(460) within the C-terminal helicase region of NS3 was cleaved more slowly. Autolytic cleavage reactions also occurred in NS2B-NS3 recombinant proteins from yellow fever virus, dengue virus types 2 and 4, and Japanese encephalitis virus. Cis and trans cleavages were distinguished using a noncleavable WNV protease variant and two types of substrates as follows: an inactive variant of recombinant WNV NS2B-NS3, and cyan and yellow fluorescent proteins fused by a dodecamer peptide encompassing a natural cleavage site. With these materials, the autolytic cleavages were found to be intramolecular only. Autolytic cleavage of the helicase site was insensitive to protein dilution, confirming that autolysis is intramolecular. Formation of an active protease was found to require neither cleavage of NS2B from NS3 nor a free NS3 N terminus. Evidence was also obtained for product inhibition of the protease by the cleaved C terminus of NS2B. PMID- 17337447 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces premature activation of the KLF2 regulon during thymocyte development. AB - The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) causes numerous and diverse toxic events via activation of the aryl hydrocarbon receptor, including atrophy of the thymus. Exposure to TCDD induces acute thymocyte cell loss, which occurs concomitantly with proliferation arrest and premature emigration of triple negative (TN; CD4(-), CD8(-), CD3(-)) T cell progenitors. In this report, we demonstrate that TCDD exposure results in dysregulation of KLF2 (Kruppel-like factor 2) expression in developing thymocytes. The Klf2 gene encodes an Sp1-like zinc finger transcription factor that functions as a central regulator of T lymphocyte proliferation and trafficking. During normal thymocyte development, KLF2 is expressed exclusively in CD4 and CD8 single positive T cells and promotes a nonproliferative, promigratory phenotype. In mice exposed to TCDD, however, the Klf2 gene is prematurely expressed in TN thymocytes. Administration of a 100 microg/kg dose of TCDD results in a approximately 15-fold induction of KLF2 as early as the TN2 (CD44(+), CD25(+)) stage of development and immediately precedes acute cell loss in the TN3, TN4, and double positive (CD4(+), CD8(+)) cell stages. Induction of KLF2 occurs within 12 h of TCDD exposure and is fully dependent on expression of the aryl hydrocarbon receptor. In addition, TCDD exposure alters the expression of several factors comprising the KLF2 regulon, including Edg1/S1P(1), beta(7) integrin, CD52, Cdkn2d (cyclin-dependent kinase inhibitor 2D), s100a4, and IL10R alpha. These findings indicate that the pollutant TCDD interferes with early thymopoeisis via ectopic expression of the KLF2 regulon. PMID- 17337449 TI - Dynamics of the S1S2 glutamate binding domain of GluR2 measured using 19F NMR spectroscopy. AB - Ionotropic glutamate receptors mediate the majority of vertebrate excitatory synaptic transmission. Although the structure of the GluR2 binding domain (S1S2) is well known (agonist binding site between two lobes), little is known about the time scales of conformational transitions or the relationship between dynamics and function. (19)F NMR ((19)F-labeled tryptophan) spectroscopy was used to monitor motions in the S1S2 domain bound to ligands with varying efficacy and in the apo state. One tryptophan (Trp-671) undergoes chemical exchange in some but not all agonists, consistent with mus-ms motion. The dynamics can be correlated to ligand affinity, and a likely source of the motion is a peptide bond capable of transiently forming hydrogen bonds across the lobe interface. Another tryptophan (Trp-767) appears to monitor motions of the relative positions of the lobes and suggests that the relative orientation in the apo- and antagonist-bound forms can exchange between at least two conformations on the ms time scale. PMID- 17337450 TI - JNK1 Is required for the induction of Mkp1 expression in macrophages during proliferation and lipopolysaccharide-dependent activation. AB - Macrophages proliferate in the presence of their growth factor, macrophage colony stimulating factor (M-CSF), in a process that is dependent on early and short ERK activation. Lipopolysaccharide (LPS) induces macrophage activation, stops proliferation, and delays ERK phosphorylation, thereby triggering an inflammatory response. Proliferating or activating responses are balanced by the kinetics of ERK phosphorylation, the inactivation of which correlates with Mkp1 induction. Here we show that the transcriptional induction of this phosphatase by M-CSF or LPS depends on JNK but not on the other MAPKs, ERK and p38. The lack of Mkp1 induction caused by JNK inhibition prolonged ERK-1/2 and p38 phosphorylation. The two JNK genes, jnk1 and jnk2, are constitutively expressed in macrophages. However, only the JNK1 isoform was phosphorylated and, as determined in single knock-out mice, was necessary for Mkp1 induction by M-CSF or LPS. JNK1 was also required for pro-inflammatory cytokine biosynthesis (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) and LPS-induced NO production. This requirement is independent of Mkp1 expression, as shown in Mkp1 knock-out mice. Our results demonstrate a critical role for JNK1 in the regulation of Mkp1 induction and in LPS-dependent macrophage activation. PMID- 17337451 TI - The subunit CSN6 of the COP9 signalosome is cleaved during apoptosis. AB - The COP9 signalosome is a large multiprotein complex that consists of eight subunits termed CSN1-CSN8. The diverse functions of the COP9 complex include regulation of several important intracellular pathways, including the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. Nod1 is also thought to be an important cytoplasmic receptor involved in innate immune responses. It detects specific motifs of bacterial peptidoglycan, and this results in activation of multiple signaling pathways and changes in cell function. In this report, we performed a yeast two-hybrid screening and discovered that Nod1 interacts with several components of the COP9 signalosome through its CARD domain. Moreover, we observed that activation of the Nod1 apoptotic pathway leads to specific cleavage of the subunit CSN6. This cleavage is concomitant with caspase processing and generates a short amino-terminal peptide of 3 kDa. A complete inhibition of this cleavage was achieved in the presence of the broad spectrum pharmacological inhibitor of apoptosis, Z-VAD. Furthermore, overexpression of CLARP, a specific caspase 8 inhibitor, completely blocked cleavage of CSN6. Taken together, these results suggest a critical role of caspase 8 in the processing of CSN6. Moreover, these findings suggest that CSN6 cleavage may result in modifications of functions of the COP9 complex that are involved in apoptosis. PMID- 17337452 TI - Engineered monomeric human histidine triad nucleotide-binding protein 1 hydrolyzes fluorogenic acyl-adenylate and lysyl-tRNA synthetase-generated lysyl adenylate. AB - Hint1 is a homodimeric protein and member of the ubiquitous HIT superfamily. Hint1 catalyzes the hydrolysis of purine phosphoramidates and lysyl-adenylate generated by lysyl-tRNA synthetase (LysRS). To determine the importance of homodimerization on the biological and catalytic activity of Hint1, the dimer interface of human Hint1 (hHint1) was destabilized by replacement of Val(97) of hHint1 with Asp, Glu, or Arg. The mutants were shown to exist as monomers in solution by a combination of size exclusion chromatograph, static light scattering, and chemically induced dimerization studies. Circular dichroism studies revealed little difference between the stability of the V97D, V97E, and wild-type hHint1. Relative to wild-type and the V97E mutant, however, significant perturbation of the V97D mutant structure was observed. hHint1 was shown to prefer 3-indolepropionic acyl-adenylate (AIPA) over tryptamine adenosine phosphoramidate monoester (TpAd). Wild-type hHint1 was found to be 277- and 1000 fold more efficient (k(cat)/K(m) values) than the V97E and V97D mutants, respectively. Adenylation of wild-type, V97D, and V97E hHint1 by human LysRS was shown to correlate with the mutant k(cat)/K(m) values using 3-indolepropionic acyl-adenylate as a substrate, but not tryptamine adenosine phosphoramidate monoester. Significant perturbations of the active site residues were not detected by molecular dynamics simulations of the hHint1s. Taken together, these results demonstrate that for hHint1; 1) the efficiency (k(cat)/K(m)) of acylated AMP hydrolysis, but not maximal catalytic turnover (k(cat)), is dependent on homodimerization and 2) the hydrolysis of lysyl-AMP generated by LysRS is not dependent on homodimerization if the monomer structure is similar to the wild type structure. PMID- 17337453 TI - Selenoprotein H is a nucleolar thioredoxin-like protein with a unique expression pattern. AB - The human selenoproteome consists of 25 known selenoproteins, but functions of many of these proteins are not known. Selenoprotein H (SelH) is a recently discovered 14-kDa mammalian protein with no sequence homology to functionally characterized proteins. By sensitive sequence and structure analyses, we identified SelH as a thioredoxin fold-like protein in which a conserved CXXU motif (cysteine separated by two other residues from selenocysteine) corresponds to the CXXC motif in thioredoxins. These data suggest a redox function of SelH. Indeed, a recombinant SelH shows significant glutathione peroxidase activity. In addition, SelH has a conserved RKRK motif in the N-terminal sequence. We cloned wild-type and cysteine mutant forms of SelH either upstream or downstream of green fluorescent protein (GFP) and localized this fusion protein to the nucleus in transfected mammalian cells, whereas mutations in the RKRK motif resulted in the cytosolic protein. Interestingly, the full-length SelH-GFP fusion protein localized specifically to nucleoli, whereas the N-terminal sequence of SelH fused to GFP had a diffuse nucleoplasm location. Northern blot analyses revealed low expression levels of SelH mRNA in various mouse tissues, but it was elevated in the early stages of embryonic development. In addition, SelH mRNA was overexpressed in human prostate cancer LNCaP and mouse lung cancer LCC1 cells. Down-regulation of SelH by RNA interference made LCC1 cells more sensitive to hydrogen peroxide but not to other peroxides tested. Overall, these data establish SelH as a novel nucleolar oxidoreductase and suggest that some functions in this compartment are regulated by redox and dependent on the trace element selenium. PMID- 17337454 TI - Dimerization is important for the GTPase activity of chloroplast translocon components atToc33 and psToc159. AB - Arabidopsis Toc33 (atToc33) is a GTPase and a member of the Toc (translocon at the outer-envelope membrane of chloroplasts) complex that associates with precursor proteins during protein import into chloroplasts. By inference from the crystal structure of psToc34, a homologue in pea, the arginine at residue 130 (Arg(130)) has been implicated in the formation of the atToc33 dimer and in intermolecular GTPase activation within the dimer. Here we report the crystal structure at 3.2-A resolution of an atToc33 mutant, atToc33(R130A), in which Arg(130) was mutated to alanine. Both in solution and in crystals, atToc33(R130A) was present in its monomeric form. In contrast, both wild-type atToc33 and another pea Toc GTPase homologue, pea Toc159 (psToc159), were able to form dimers in solution. Dimeric atToc33 and psToc159 had significantly higher GTPase activity than monomeric atToc33, psToc159, and atToc33(R130A). Molecular modeling using the structures of psToc34 and atToc33(R130A) suggests that, in an architectural dimer of atToc33, Arg(130) from one monomer interacts with the beta phosphate of GDP and several other amino acids of the other monomer. These results indicate that Arg(130) is critical for dimer formation, which is itself important for GTPase activity. Activation of GTPase activity by dimer formation is likely to be a critical regulatory step in protein import into chloroplasts. PMID- 17337455 TI - Racial variation in the association between gestational age and perinatal mortality: prospective study. AB - OBJECTIVES: To determine if the risks of perinatal mortality and antepartum stillbirth associated with post term birth increase earlier during pregnancy in South Asian and black women than in white women, and to investigate differences in the factors associated with antepartum stillbirth between the racial groups. DESIGN: Prospective study using logistic regression analysis. SETTING: 15 maternity units in northwest London from 1988 to 2000. PARTICIPANTS: 197 061 nulliparous women self reported as white, South Asian, or black, who delivered a single baby weighing at least 500 g at 24-43 completed weeks' gestation. MAIN OUTCOME MEASURES: Gestation specific perinatal mortality, antepartum stillbirth rates, and independent factors for antepartum stillbirth by racial groups. Results The crude gestation specific perinatal mortality patterns for the three racial groups differed (P<0.001). The perinatal mortality rate among black women was lower than among white women before 32 weeks but was higher thereafter. Perinatal mortality was highest among South Asian women at all gestational ages and increased the fastest at term. After adjusting for the confounders of antepartum stillbirth (placental abruption, congenital abnormality, low birth weight, birth weight <10th centile, meconium passage, fever, maternal body mass index > or =30, and maternal age > or =30), the excess mortality among black women after 32 weeks was not significant. After adjusting for confounding, South Asian women still had a significantly higher risk of antepartum stillbirth (odds ratio 1.8, 95% confidence interval 1.2 to 2.7). Conclusions The risk of perinatal mortality increased earlier in gestation among South Asian women than among white women. The most important factor associated with antepartum stillbirth among white women was placental abruption, but among South Asian and black women it was birth weight below 2000 g. PMID- 17337456 TI - Birth order of twins and risk of perinatal death related to delivery in England, Northern Ireland, and Wales, 1994-2003: retrospective cohort study. AB - OBJECTIVE: To determine the effect of birth order on the risk of perinatal death in twin pregnancies. DESIGN: Retrospective cohort study. SETTING: England, Northern Ireland, and Wales, 1994-2003. PARTICIPANTS: 1377 twin pregnancies with one intrapartum stillbirth or neonatal death from causes other than congenital abnormality and one surviving infant. MAIN OUTCOME MEASURES: The risk of perinatal death in the first and second twin estimated with conditional logistic regression. RESULTS: There was no association between birth order and the risk of death overall (odds ratio 1.0, 95% confidence interval 0.9 to 1.1). However, there was a highly significant interaction with gestational age (P<0.001). There was no association between birth order and the risk of death among infants born before 36 weeks' gestation but there was an increased risk of death among second twins born at term (2.3, 1.7 to 3.2, P<0.001), which was stronger for deaths caused by intrapartum anoxia or trauma (3.4, 2.2 to 5.3). Among term births, there was a trend (P=0.1) towards a greater risk of the second twin dying from anoxia among those delivered vaginally (4.1, 1.8 to 9.5) compared with those delivered by caesarean section (1.8, 0.9 to 3.6). CONCLUSIONS: In this cohort, compared with first twins, second twins born at term were at increased risk of perinatal death related to delivery. Vaginally delivered second twins had a fourfold risk of death caused by intrapartum anoxia. PMID- 17337457 TI - Cost effectiveness analysis of minimally invasive internal thoracic artery bypass versus percutaneous revascularisation for isolated lesions of the left anterior descending artery. AB - OBJECTIVE: To compare the cost effectiveness of percutaneous transluminal coronary artery stenting with minimally invasive internal thoracic artery bypass for isolated lesions of the left anterior descending artery. DESIGN: Cost effectiveness analysis. DATA SOURCES: Embase, Medline, Cochrane, Google Scholar, and Health Technology Assessment databases (1966-2005), and reference sources for utility values and economical variables. METHODS: Decision analytical modelling and Markov simulation were used to model medium and long term costs, quality of life, and cost effectiveness after either intervention using data from referenced sources. Probabilistic sensitivity and alternative analyses were used to investigate the effect of uncertainty about the value of model variables and model structure. RESULTS: Stenting was the dominant strategy in the first two years, being both more effective and less costly than bypass surgery. In the third year bypass surgery still remained more expensive but became marginally more effective. As the incremental cost effectiveness was 1,108,130.40 pounds sterling (1 682,146.00 euros; $2,179,194) per quality adjusted life year (QALY), the additional effectiveness could not be said to justify the additional cost at this stage. By five years, however, the incremental cost effectiveness ratio of 28,042.95 pounds sterling per QALY began to compare favourably with other interventions. At 10 years the additional effectiveness of 0.132 QALYs (range 0.166 to 0.430) probably justified the additional cost of 829.02 pounds sterling (range 205.56 pounds sterling to 1452.48 pounds sterling), with an incremental cost effectiveness of 6274.02 pounds sterling per QALY. Sensitivity and alternative analysis showed the results were sensitive to the time horizon and stent type. CONCLUSIONS: Minimally invasive left internal thoracic artery bypass may be a more cost effective medium and long term alternative to percutaneous transluminal coronary artery stenting. PMID- 17337458 TI - Meta-analysis of minimally invasive internal thoracic artery bypass versus percutaneous revascularisation for isolated lesions of the left anterior descending artery. AB - OBJECTIVE: To compare outcomes between minimally invasive left internal thoracic artery bypass and percutaneous coronary artery stenting as primary interventions for isolated lesions of the left anterior descending artery. DESIGN: Meta analysis of randomised and non-randomised comparative peer reviewed publications. DATA SOURCES: Embase, Medline, Cochrane, Google Scholar, and Health Technology Assessment databases (1966-2005). REVIEW METHODS: Studies comparing the two procedures as the primary intervention for isolated left anterior descending artery stenosis were identified and the following extracted: study design, population characteristics, severity of coronary artery disease, cardiovascular risk factors, and outcomes of interest. RESULTS: 12 studies (1952 patients) reporting results from eight groups were included: one was a retrospective design, one prospective non-randomised, and six prospective randomised. Meta analysis of randomised trials showed a higher rate of recurrence of angina (odds ratio 2.62, 95% confidence interval 1.32 to 5.21), incidence of major adverse coronary and cerebral events (2.86, 1.62 to 5.08), and need for repeat revascularisation (4.63, 2.52 to 8.51) with percutaneous stenting. No significant difference was found in myocardial infarction, stroke, or mortality at maximum follow-up between interventions. CONCLUSIONS: Minimally invasive left internal thoracic artery bypass for isolated lesions of the left anterior descending artery resulted in fewer complications in the mid-term compared with percutaneous transluminal coronary artery stenting. PMID- 17337459 TI - A numerical method of reconstructing the pollutant concentration field in a ventilated room. AB - Pollutant source emission flow rates in the workplace are typically unknown in occupational hygiene. Similarly, a restricted number of concentration measurements can provide only spatial limited information on the pollutant distribution in the room. This paper presents a numerical method to evaluate the intensities of pollutant sources and to reconstruct the associated concentration field at every point of a ventilated enclosure containing one or several pollutant sources of unknown emission rate. This reconstructed concentration field is obtained both from the geometric and ventilation characteristics of the enclosure and from a limited number of fixed-station concentration measurements. The method is currently applicable to steady situations. The predictions obtained are then compared with concentration measurements in a laboratory closed cabin under controlled ventilation. Pollutant sources generated tracer gas emissions at known flow rates. Comparisons were performed successively for three different physical configurations. PMID- 17337460 TI - A pooled analysis to study trends in exposure to antineoplastic drugs among nurses. AB - OBJECTIVES: Several studies have shown that exposure to antineoplastic drugs can cause toxic effects on reproductive health as well as carcinogenic effects. Numerous studies have corroborated that hospital workers are exposed to these drugs. This study focused on trends in exposure to antineoplastic drugs since the introduction of guidelines in The Netherlands. METHODS: Data from three cross sectional exposure surveys conducted in The Netherlands were pooled to examine trends in occupational exposure to cyclophosphamide. Nurses' 24 h urine samples were analyzed in separate fractions, surface contamination was determined and gloves used during preparation or while handling patient urine were collected. The difference in detectable urine samples between 1997 and 2000 was determined by a generalized estimating equations (GEE) binomial regression model. Mixed models were used to study the time trend in surface and glove contamination levels. RESULTS: The percentage of nurses' urine samples with detectable cyclophosphamide had decreased 4-fold between 1997 and 2000. Median cyclophosphamide levels in the positive urine samples were 3-fold lower in 2000 than in 1997. Surface and glove contamination had statistically significantly decreased between 1997 and more recent years. CONCLUSIONS: Nurses working at outpatient clinics or oncology wards are still being exposed to cyclophosphamide, but their exposure decreased considerably between 1997 and 2000, presumably due to the introduction of detailed guidelines and regulations in The Netherlands, the subsequent increased use of LuerLock connections and infusion systems prefilled with saline, and growing hazard awareness of nurses working with antineoplastic drugs. PMID- 17337461 TI - Racial differences in respirator fit testing: a pilot study of whether American fit panels are representative of Chinese faces. AB - The current respirator fit test panels (RFTPs) developed by Los Alamos National Laboratory or improved by the National Institute for Occupational Safety and Health were based on facial anthropometric survey of American groups including few Chinese examples. Facial anthropometric dimensions for other race/ethnic groups are different. Despite the fact that China has been the largest national source of industrial labor supply, and Chinese is one of top 10 races for immigration to America and Britain, there have been few related facial anthropometric studies on RFTPs for Chinese. This pilot study was conducted to investigate the difference of facial anthropometric dimensions between Chinese and Americans, and whether American RFTPs are applicable to Chinese. The results show that facial anthropometric measurements of 461 Chinese subjects are different from those of American groups described in the literature. About 12-35% of the Chinese subjects fall outside the ranges derived from American panels. Chinese may have shorter and wider facial character than American groups. Current RFTPs, which are based on American facial anthropometric surveys, may not fairly represent the facial anthropometric characteristics of Chinese groups. The results can also help to construct new RFTPs for Chinese in the future. Further studies are needed to verify whether the results in this study would be in agreement with those of facial anthropometric survey in wider samples. PMID- 17337462 TI - Assessing management of musculoskeletal disorders in the ambulance service. AB - BACKGROUND: Musculoskeletal disorders (MSDs) are the most common occupational illness in Great Britain affecting 1.1 million people a year. Paramedics, in particular, are known to have a high incidence of MSDs resulting, for many, in early retirement. AIM: To explore the management of MSDs at two ambulance services with respect to the implementation of policies and experience of staff. METHODS: The data were collected at two ambulance services using document retrieval and semi-structured interviews. The first service used a functional centred occupational health (OH) approach with patient participation. The second service used a more traditional medical model with the patient in a more passive role. RESULTS: The first service reported their MSD management policies and procedures concurred with 28 of the 32 Faculty of Occupational Medicine guidelines (88%) in contrast to the second service, where only 17 (53%) concurred. For both services, the expected recovery pathways (management policies and procedures) had points of variance with the experienced recovery pathways. Both services had haphazard referral to OH resulting in limited referral for treatment in the first 4 weeks post-injury and no difference in median recovery times. These variances resulted in a convergence in the timing and type of treatment received by staff at both services. CONCLUSIONS: Both ambulance services were found to have variance in the experienced recovery pathway in comparison to the expected pathway. It was concluded that without systematic monitoring and regular audit, there was likely to be a lack of compliance with the policy and procedures. PMID- 17337463 TI - IL23R Arg381Gln is associated with childhood onset inflammatory bowel disease in Scotland. PMID- 17337464 TI - Body mass index, height and risk of adenocarcinoma of the oesophagus and gastric cardia: a prospective cohort study. AB - BACKGROUND: In the last decades, the incidence of oesophageal and gastric cardia adenocarcinoma has increased rapidly in the Western world. We investigated the association between body mass index (BMI), height and risk of oesophageal and gastric cardia adenocarcinoma. METHODS: The Netherlands Cohort Study was initiated in 1986. All participants (n = 120,852), aged 55-69 years, completed a self administered questionnaire. Cases were identified through annual record linkage with the Netherlands Cancer Registry. After 13.3 years of follow-up, excluding the first follow-up year, complete data from 4552 subcohort members, 133 oesophageal and 163 gastric cardia adenocarcinomas were available for case cohort analyses. Incidence rate ratios (RRs) and corresponding 95% confidence intervals were estimated using Cox proportional hazard models. RESULTS: The RRs (95% CI) of oesophageal adenocarcinoma were 1.40 (0.95 to 2.04) and 3.96 (2.27 to 6.88) for overweight (BMI 25.0-29.9 kg/m(2)) and obese subjects (BMI >or=30.0 kg/m(2)), respectively, compared to subjects with normal weight (BMI 20.0-24.9 kg/m(2)). For gastric cardia adenocarcinoma, these RRs were 1.32 (0.94 to 1.85) and 2.73 (1.56 to 4.79). Also change in BMI during adulthood was positively associated with the risk of oesophageal and gastric cardia adenocarcinoma (p trend 0.001 and 0.02, respectively), while no association was found with BMI in early adulthood (p trend 0.17 and 0.17, respectively). None of the tumour types investigated was significantly associated with height. CONCLUSIONS: These results confirm higher risks of oesophageal and gastric cardia adenocarcinoma with increasing BMI. This implies that the increasing prevalence of obesity may be one of the explanations for the rising incidence of oesophageal and gastric cardia adenocarcinoma in the Western world. PMID- 17337465 TI - Pure red cell aplasia followed by disseminated intravascular coagulation in a haemodialysis patient receiving erythropoietin-beta. PMID- 17337466 TI - Neural cell adhesion molecule expression on renal interstitial cells. AB - BACKGROUND: At early stages of kidney development, the neural cell adhesion molecule (NCAM) is highly expressed on cells of the metanephrogenic mesenchyme. During maturation of the fetal kidney, NCAM gradually disappears. So far, it has been widely accepted that NCAM in the adult kidney is only expressed by nerves, and not by other cell types. METHODS: NCAM expression was analysed in human adult healthy and diseased kidneys by immunohistochemistry and western blot analysis. NCAM+ renal interstitial cells were further characterized by double immunofluorescent staining using antibodies against neurofilaments, alpha smooth muscle actin, vimentin, alpha5beta1 integrin, CD68, CD11c, HLA-DR and the potential progenitor cell markers CD34, CD117, CD133, CD24, nestin and cadherin 11. RESULTS: In adult human kidneys, NCAM expression is restricted to rare interstitial cells with dendritic morphology, which are neurofilament-negative and predominantly localized on the corticomedullary junction. They are also negative for fibroblast cell markers, but co-express the haematopoietic stem cell markers CD34 and CD133. The number of NCAM+ interstitial cells increased in the initial phases of interstitial fibrosis. Western blot analysis of renal tissues with incipient interstitial fibrosis tissues showed the expression of the 140 kDa NCAM isoform. CONCLUSIONS: These data indicate that a rare subpopulation of NCAM+ interstitial cells could represent renal progenitors, and that NCAM+ interstitial cells can participate in the initial phase of interstitial fibrosis. PMID- 17337467 TI - Detection of HP10 antigen in serum for diagnosis and follow-up of subarachnoidal and intraventricular human neurocysticercosis. AB - INTRODUCTION: Neurocysticercosis (NC), a parasitic disease caused by Taenia solium, may be either asymptomatic or show a mild to severe clinical picture with intracranial hypertension. The most severe form of the disease is caused when viable cysticerci are localised in the ventricles or in subarachnoidal cisterns at the base of the skull. Detection of the secreted metacestode antigen HP10 in cerebrospinal fluid is a sensitive and specific method for the diagnosis of these severe NC cases. OBJECTIVE AND METHODS: To evaluate the validity of HP10 antigen detection ELISA when applied to serum, using paired serum and cerebrospinal fluid samples from 116 radiologically and clinically characterised NC patients. RESULTS: The HP10 antigen assay exhibited a similarly high sensitivity in identifying severe NC cases from sera (84.8%) and CSF (91.3%). In contrast, HP10 antigen was rarely detected in asymptomatic or mild NC cases (3 of 57). Importantly, the HP10 antigen assay applied to serum showed high specificity (94%) when used in 126 serum samples of non-NC subjects from an endemic community with a confirmed coproparasitological diagnosis of intestinal parasitic infections. Finally, the HP10 assay also proved to be of value in the follow-up of treated patients. CONCLUSION: This study confirms that detection of the metacestode HP10 antigen in serum is a useful tool for diagnosis and follow-up of patients with severe forms of NC treated with cysticidal drugs. PMID- 17337468 TI - Commentary: First steps in molecular epidemiology: Lower et al. 1979. PMID- 17337469 TI - Living arrangements. PMID- 17337470 TI - Anti-Mullerian hormone and anti-Mullerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women. AB - BACKGROUND: In mice, anti-Mullerian hormone (AMH) inhibits primordial follicle recruitment and decreases FSH sensitivity. Little is known about the role of AMH in human ovarian physiology. We hypothesize that in women AMH has a similar role in ovarian function as in mice and investigated this using a genetic approach. METHODS: The association of the AMH Ile(49)Ser and the AMH type II receptor (AMHR2) -482 A > G polymorphisms with menstrual cycle characteristics was studied in a Dutch (n = 32) and a German (n = 21) cohort of normo-ovulatory women. RESULTS: Carriers of the AMH Ser(49) allele had higher serum estradiol (E(2)) levels on menstrual cycle day 3 when compared with non-carriers in the Dutch cohort (P = 0.012) and in the combined Dutch and German cohort (P = 0.03). Carriers of the AMHR2 -482G allele also had higher follicular phase E(2) levels when compared with non-carriers in the Dutch cohort (P = 0.028), the German cohort (P = 0.048) and hence also the combined cohort (P = 0.012). Women carrying both AMH Ser(49) and AMHR2 -482G alleles had highest E(2) levels (P = 0.001). For both polymorphisms no association with serum AMH or FSH levels was observed. CONCLUSIONS: Polymorphisms in the AMH and AMHR2 genes are associated with follicular phase E(2) levels, suggesting a role for AMH in the regulation of FSH sensitivity in the human ovary. PMID- 17337471 TI - Levonorgestrel pharmacokinetics in plasma and milk of lactating women who take 1.5 mg for emergency contraception. AB - BACKGROUND: Progestin-only methods are among the contraceptive options available for breastfeeding women, however the doses of progestin used in emergency contraception (EC) have not been evaluated in nursing mothers. We therefore investigated the pharmacokinetics of 1.5 mg levonorgestrel (LNG) in lactating women. METHODS: Twelve healthy exclusively breastfeeding volunteers received 1.5 mg LNG. Women refrained from nursing for 72 h after dosing and fed their infants with milk frozen beforehand. Serial blood and milk samples were collected for 120 h and assayed for LNG and sex hormone binding globulin. RESULTS: LNG concentrations peaked in plasma and in milk 1-4 h and 2-4 h after dosing, respectively. Concentrations in milk (M) paralleled those in plasma (P) but were consistently lower (mean M:P ratio 0.28). Estimated infant exposure to LNG is 1.6 microg on the day of dosing (1 microg in the first 8 h), 0.3 microg on the second day and 0.2 microg on the third day. CONCLUSIONS: Nursing mothers may need EC. These results suggest that to limit infant exposure to the period of maximum LNG excretion in milk, mothers should discontinue nursing for at least 8 h, but not more than 24 h, after EC. PMID- 17337472 TI - Molecular glass wool filtration as a new tool for sperm preparation. AB - BACKGROUND: Magnetic-activated cell sorting (MACS) using annexin V-conjugated microbeads in a liquid phase eliminates apoptotic spermatozoa based on the externalization of phosphatidylserine (EPS) residues. The procedure allows the enrichment of a sperm population free of apoptosis markers, giving higher fertilization potential. Our aim was to determine if the annexin V binding principle can be transferred onto a glass wool filter system in order to produce a solid phase filter. METHODS: Semen samples (n = 42) were subjected to a molecular glass wool filter system using glass surfaces coated with annexin V and compared with aliquots separated by conventional glass wool, as well as with annexin V-MACS. The extent of apoptosis was assessed by measuring levels of activated caspase 3 using fluorescein-labelled inhibitors of caspase, alterations in mitochondrial membrane potential (MMP) using a lipophilic cationic dye, and EPS using a fluorescein isothiocyanate-coupled monoclonal antibody. RESULTS: Annexin V-negative sperm filtered out by the newly developed molecular glass wool filtration (GWF) system displayed superior quality in terms of high MMP integrity, as well as, to a small extent, caspase 3 activation and EPS. CONCLUSIONS: The effect of traditional GWF can be further improved by combination with annexin V binding. This newly developed solid phase molecular filter system has been proven to enrich spermatozoa free of apoptosis markers to the same extent as the annexin V magnetic separation technique. The selection of spermatozoa free of apoptosis markers by molecular glass wool filters may enhance the results of IVF. PMID- 17337473 TI - Assessment of the 2006 revised antiphospholipid syndrome classification criteria. AB - OBJECTIVE: To analyse antiphospholipid (aPL) antibody-positive patients using the 2006 revised antiphospholipid syndrome (APS) classification criteria. METHODS: A descriptive study of 200 aPL-positive patients identified in a local, hospital based registry, analysing demographic, clinical and aPL characteristics. Patients were analysed for (1) fulfillment of the 1999 original (Sapporo) and 2006 revised APS classification criteria; (2) non-criteria aPL features (for all aPL-positive patients, based on the 2006 revised criteria definitions); and (3) non-aPL thrombosis risk factors at the time of the clinical events (for patients with APS, based on the 2006 revised criteria stratifications). RESULTS: Of the 200 patients, 183 patients had sufficient data for analysis. Of these, 39 (21%) patients did not meet the laboratory requirement of the original 1999 criteria. Of 81 patients with APS who met the 1999 classification criteria, 47 (58%) also met the 2006 revised criteria. Of 63 asymptomatic (no vascular or pregnancy events) aPL-positive patients who met the laboratory requirement of the 1999 classification criteria, 38 (60%) also met the laboratory requirement of the 2006 revised criteria. More than 50% of the patients with APS with vascular events had identifiable non-aPL thrombosis risk factors at the time of clinical events. CONCLUSIONS: Only 59% of the patients meeting the 1999 APS Sapporo classification criteria met the 2006 APS classification criteria. The revised criteria will have positive implications in APS research by way of limiting the inclusion of a heterogeneous group of patients and also by way of providing a risk-stratified approach. PMID- 17337474 TI - Anti-tumour necrosis factor alpha therapy in patients with impaired renal function. PMID- 17337475 TI - Resolving the blind spot of transoesophageal echocardiography: a new diagnostic device for visualizing the ascending aorta in cardiac surgery. AB - BACKGROUND: Atherosclerosis of the ascending aorta (AA) and stroke after cardiac surgery are related. Knowledge of the location of AA-atherosclerosis pre sternotomy allows changes in surgical strategy to avoid manipulation of the AA. The gold-standard for assessment of AA-atherosclerosis is intraoperative epiaortic ultrasound scanning (EUS). Transoesophageal echocardiography (TOE) is unable to detect atherosclerosis in the distal AA due to the 'blind spot'. A new method [A-View (Aortic-view) method] using a fluid-filled catheter may enhance the assessment of distal AA-atherosclerosis. The aim of this study was to evaluate whether the A-View method indeed visualizes the distal AA and to assess the safety of this technology. METHODS: In a cross-sectional diagnostic study, 41 patients undergoing cardiac surgery including sternotomy underwent the same work up including TOE, the A-View method, EUS, and routine operative monitoring. RESULTS: With the A-View method, the distal AA was visible in all (100%) patients. There were no clinical important side-effects associated with the use of the A-View catheter; however, in one patient the endotracheal tube was accidentally dislocated leading to a decrease in Sa(O2). Severity of atherosclerosis visualized with the A-View method compared with EUS results showed good agreement between the two methods [Kappa of 0.69 (0.50-0.88)]. The Bland-Altman analysis showed poor agreement in plaque-size measurements (bias 0.05 cm2, limits of agreement - 0.63 to 0.74 cm2). CONCLUSIONS: The A-View method offers a minimally invasive and safe approach to preoperatively resolving the blind spot of TOE. Compared with EUS, the A-View method yielded satisfactory results in the detection of AA-atherosclerosis. The A-View method seems a promising tool for patients undergoing cardiac surgery to direct surgical management. PMID- 17337476 TI - The importance of fibroblasts in remodelling of the human uterine cervix during pregnancy and parturition. AB - It is well established that fibroblasts play a crucial role in pathophysiological extracellular matrix remodelling. The aim of this project is to elucidate their role in normal physiological remodelling. Specifically, the remodelling of the human cervix during pregnancy, resulting in an enabled passage of the child, is used as the model system. Fibroblast cultures were established from cervices of non-pregnant women, women after 36 weeks of pregnancy and women directly after partus. The cells were immunostained and quantified by western blots for differentiation markers. The cultures were screened for cytokine and metalloproteinase production and characterized by global proteome analysis. The cell cultures established from partal donors differ significantly from those from non-pregnant donors, which is in accordance with in vivo findings. A decrease in alpha-smooth actin and prolyl-4-hydroxylase and an increase in interleukin (IL) 6, IL-8 and matrix metalloproteinases (MMP)-1 and MMP-3 were observed in cultures from partal donors. 2D-gel electrophoresis followed by mass spectrometry showed that the expression of 59 proteins was changed significantly in cultures of partal donors. The regulated proteins are involved in protein kinase C signalling, Ca2+ binding, cytoskeletal organization, angiogenesis and degradation. Our data suggest that remodelling of the human cervix is orchestrated by fibroblasts, which are activated or recruited by the inflammatory processes occurring during the ripening cascade. PMID- 17337477 TI - Endometrial bleeding. AB - Abnormal bleeding is a significant health problem, especially during adolescence and before menopause when anovulatory cycles are common. Curettage is rarely necessary to investigate or treat menstrual problems in adolescents, and its use should also be minimized in women younger than 40 years. In every age group, medical treatment is the initial choice, but surgical treatment by endometrial destruction or hysterectomy is sometimes required. Benign causes of bleeding include fibroids and possibly adenomyosis, but the indications for treatment in each case depend upon the extent of bleeding, not the extent of the lesion. Breakthrough bleeding (BTB) with combined oral contraceptives commonly leads to discontinuation of the method. As BTB tends to improve with time, in the first 3 months of pill use, unless there are obvious underlying causes, women should be reassured that it will likely settle. BTB is often the reason for discontinuing progestogen-only contraception, and there is a need for effective means of treating unscheduled bleeding. Bleeding occurs in approximately 3% of post menopausal women, and the use of hormones increases the likelihood of bleeding by >5-fold. Knowledge of the underlying mechanisms of bleeding is essential to the development of effective treatment. PMID- 17337478 TI - Cognitive function and menopausal hormone therapy. PMID- 17337479 TI - Properties of a tobacco DNA methyltransferase, NtMET1 and its involvement in chromatin movement during cell division. AB - BACKGROUND AND AIMS: Plants possess three types of DNA methyltransferase, among which methyltransferase type 1 (MET1) is considered to play a major role by maintaining the CpG methylation patterns. However, little information is available as to its enzymatic activity, interacting proteins and spatial and temporal behaviours during DNA replication. In the present study, one example, NtMET1 from tobacco plants, was selected and an analysis was made of its biochemical properties and cellular localization. METHODS: NtMET1 was expressed in Sf9 insect cells, and a purified sample was subjected to a standard in vitro methylation assay. Intramolecular interaction was examined by the yeast two hybrid and pull-down assays. Transgenic tobacco plants (Nicotiana tabacum) over expressing NtMET1 were constructed via Agrobacterium-mediated transformation. Cellular localization was examined by fluorescence protein fusion, which was expressed in tobacco bright yellow 2 cells. KEY RESULTS: In vitro assays showed no detectable methylation activity when both hemimethylated and unmethylated DNA samples were used as the substrate. In planta assays with over-expressing transgenic lines showed no hypermethylation but rather hypomethylation of genomc DNA. The inability of methylation was conceivably due to a tight intramolecular interaction between the N- and C-terminal regions with the catalytic domain residing on the C-terminus being completely masked. Cellular localization analyses indicated that NtMET1 localized to the nucleus in the resting stage and migrates to the cytoplasm during mitosis, particularly at metaphase. The pattern observed resembled that of Ran GTPase, and in vitro pull-down assays showed a clear interaction between NtMET1 and AtRAN3, an Arabidopsis orthologue of tobacco Ran GTPase, NtRan-A1. CONCLUSIONS: The results suggest that enzymatic activity of NtMET1 is well adjusted by its own intra/intermolecular interaction and perhaps by interactions with other proteins, one of which was found to be Ran GTPase. Results also revealed that NtMET1 becomes localized to the vicinity of chromatin with the aid of Ran GTPase during cell division, and may play an important role in progress through mitosis independently of methylation activity. PMID- 17337480 TI - Distribution and phylogenetic significance of the 71-kb inversion in the plastid genome in Funariidae (Bryophyta). AB - BACKGROUND AND AIMS: The recent assembly of the complete sequence of the plastid genome of the model taxon Physcomitrella patens (Funariaceae, Bryophyta) revealed that a 71-kb fragment, encompassing much of the large single copy region, is inverted. This inversion of 57% of the genome is the largest rearrangement detected in the plastid genomes of plants to date. Although initially considered diagnostic of Physcomitrella patens, the inversion was recently shown to characterize the plastid genome of two species from related genera within Funariaceae, but was lacking in another member of Funariidae. The phylogenetic significance of the inversion has remained ambiguous. METHODS: Exemplars of all families included in Funariidae were surveyed. DNA sequences spanning the inversion break ends were amplified, using primers that anneal to genes on either side of the putative end points of the inversion. Primer combinations were designed to yield a product for either the inverted or the non-inverted architecture. KEY RESULTS: The survey reveals that exemplars of eight genera of Funariaceae, the sole species of Disceliaceae and three generic representatives of Encalyptales all share the 71-kb inversion in the large single copy of the plastid genome. By contrast, the plastid genome of Gigaspermaceae (Funariales) is characterized by a gene order congruent with that described for other mosses, liverworts and hornworts, and hence it does not possess this inversion. CONCLUSIONS: The phylogenetic distribution of the inversion in the gene order supports a hypothesis only weakly supported by inferences from sequence data whereby Funariales are paraphyletic, with Funariaceae and Disceliaceae sharing a common ancestor with Encalyptales, and Gigaspermaceae sister to this combined clade. To reflect these relationships, Gigaspermaceae are excluded from Funariales and accommodated in their own order, Gigaspermales order nov., within Funariideae. PMID- 17337481 TI - Coincidence of small-scale spatial discontinuities in leaf morphology and nuclear microsatellite variation of Quercus petraea and Q. robur in a mixed forest. AB - BACKGROUND AND AIMS: The taxon complex comprising Quercus petraea and Q. robur shows distinct morphologies and ecological preferences, but mostly low differentiation in various types of molecular markers at a broad spatial range. Local, spatially explicit analyses may reveal patterns induced by microevolutionary processes operating mainly over short distances. However, no attempts have been made to date to explore the potential of spatial analyses combining morphological and genetic data of these oaks. METHODS: A mixed oak stand was studied to elucidate the small-scale population genetic structure. All adult individuals were classified and putative hybrids were identified using multivariate discrimination analysis of leaf morphological characters. Likewise, all trees were genotyped with five nuclear microsatellites, and a Bayesian assignment method was applied based on maximum likelihood of multilocus genotypes for taxon and putative hybrid classification. KEY RESULTS: Multivariate analyses of leaf morphological data recognized two groups with few individuals as putative hybrids. These groups were significantly differentiated at the five microsatellites, and genetic taxon assignment coincided well with morphological classification. Furthermore, most putative hybrids were assigned to the taxon found in their spatial neighbourhood. When grouping trees into clusters according to their spatial positions, these clusters were clearly dominated by one taxon. Discontinuities in morphological and genetic distance matrices among these clusters showed high congruence. CONCLUSIONS: The spatial-genetic analyses and the available literature led to the assumption that reproductive barriers, assortative mating, limited seed dispersal and microsite-induced selection in favour of the locally adapted taxon at the juvenile stage may reinforce taxon specific spatial aggregation that fosters species separation. Thus, the results tend to support the hypothesis that Q. petraea and Q. robur are distinct taxa which share a recent common ancestry. Occasional hybrids are rarely found in adults owing to selection during establishment of juveniles. PMID- 17337482 TI - Neural regions essential for distinct cognitive processes underlying picture naming. AB - We hypothesized that distinct cognitive processes underlying oral and written picture naming depend on intact function of different, but overlapping, regions of the left hemisphere cortex, such that the distribution of tissue dysfunction in various areas can predict the component of the naming process that is disrupted. To test this hypothesis, we evaluated 116 individuals within 24 h of acute ischaemic stroke using a battery of oral and written naming and other lexical tests, and with magnetic resonance diffusion and perfusion imaging to identify the areas of tissue dysfunction. Discriminant function analysis, using the degree of hypoperfusion in various Brodmann's areas--BA 22 (including Wernicke's area), BA 44 (part of Broca's area), BA 45 (part of Broca's area), BA 21 (inferior temporal cortex), BA 37 (posterior, inferior temporal/fusiform gyrus), BA 38 (anterior temporal cortex) and BA 39 (angular gyrus)--as discriminant variables, classified patients on the basis of the primary component of the naming process that was impaired (defined as visual, semantics, modality independent lexical access, phonological word form, orthographic word form and motor speech by the pattern of performance and types of errors across lexical tasks). Additionally, linear regression analysis demonstrated that the areas contributing the most information to the identification of patients with particular levels of impairment in the naming process were largely consistent with evidence for the roles of these regions from functional imaging. This study provides evidence that the level of impairment in the naming process reflects the distribution of tissue dysfunction in particular regions of the left anterior, inferior and posterior middle/superior temporal cortex, posterior inferior frontal and inferior parietal cortex. While occipital cortex is also critical for picture naming, it is likely that bilateral occipital damage is necessary to disrupt visual recognition. These findings provide new evidence that a network of brain regions supports naming, but separate components of this network are differentially required for distinct cognitive processes or representations underlying the complex task of naming pictures. PMID- 17337483 TI - Zaspopathy in a large classic late-onset distal myopathy family. AB - Distal myopathies have been associated with mutations in titin, dysferlin, GNE, desmin and myosin. Of these, only titin mutations were previously known to cause dominant late-onset distal myopathy. Recent findings, however, have indicated that patients affected with myofibrillar myopathy have a more distal than proximal muscle phenotype and a proportion of these may have mutations in myotilin, ZASP or filamin C, besides previously known desmin and alphaB crystallin. Here we report that the disorder in one of the well-characterized autosomal dominant distal myopathy families, the Markesbery et al. family, first reported in 1974, is caused by ZASP mutation A165V. Previous linkage to the titin locus 2q31 proved incorrect. ZASP expression by immunoblotting shows normal presence of the main 32 and 78 kDa bands and immunohistochemistry in patients reveals normal Z-disc localization except for moderate accumulations together with myotilin, desmin alphaB-crystallin and alpha-actinin. Muscle imaging reveals involvement in both the posterior and anterior compartments of the lower leg and considerable affection of proximal leg muscles at later stages. Haplotype studies in this family and in five other unrelated families with European ancestry carrying the identical A165V mutation share common markers at the locus suggesting the existence of a founder mutation. PMID- 17337484 TI - Immunotherapy for Guillain-Barre syndrome: a systematic review. AB - Guillain-Barre syndrome (GBS) is an acute inflammatory disorder of the peripheral nervous system thought to be due to autoimmunity for which immunotherapy is usually prescribed. To provide the best evidence on which to base clinical practice, we systematically reviewed the results of randomized trials of immunotherapy for GBS. We searched the Cochrane Library, MEDLINE and EMBASE in July 2006 and used the methods of the Cochrane Neuromuscular Disease Group to extract and synthesize data. Almost all trials used a 7-point disability grade scale. In four trials with altogether 585 severely affected adult participants, those treated with plasma exchange (PE) improved significantly more on this scale 4 weeks after randomization than those who did not, weighted mean difference (WMD) -0.89 (95% confidence interval (CI) -1.14 to -0.63). In five trials with altogether 582 participants, the improvement on the disability grade scale with intravenous immunoglobulin (IVIg) was very similar to that with PE, WMD -0.02 (95% CI -0.25 to 0.20). There was also no significant difference between IVIg and PE for any of the other outcome measures. In one trial with 148 participants, following PE with IVIg did not produce significant extra benefit. Limited evidence from three open trials in children suggested that IVIg hastens recovery compared with supportive care alone. Corticosteroids were compared with placebo or supportive treatment in six trials with altogether 587 participants. There was significant heterogeneity in the analysis of these trials which could be accounted for by analysing separately four small trials of oral corticosteroids with altogether 120 participants, in which there was significantly less improvement after 4 weeks with corticosteroids than without, WMD -0.82 (95% CI 0.17 to -1.47), and two large trials of intravenous methylprednisolone with altogether 467 participants, in which there was no significant difference between corticosteroids and placebo WMD -0.17 (95% CI 0.06 to -0.39). None of the treatments significantly reduced mortality. Since approximately 20% of patients die or have persistent disability despite immunotherapy, more research is needed to identify better treatment regimens and new therapeutic strategies. PMID- 17337485 TI - Lafora disease proteins malin and laforin are recruited to aggresomes in response to proteasomal impairment. AB - Lafora disease (LD), an autosomal recessive neurodegenerative disorder, is characterized by the presence of cytoplasmic polyglucosan inclusions known as Lafora bodies in several tissues including the brain. Laforin, a protein phosphatase, and malin, an ubiquitin ligase, are two of the proteins that are known to be defective in LD. Malin interacts with laforin and promotes its polyubiquitination and degradation. Here we show that malin and laforin co localize in endoplasmic reticulum (ER) and that they form centrosomal aggregates when treated with proteasomal inhibitors in both neuronal and non-neuronal cells. Laforin/malin aggregates co-localize with gamma-tubulin and cause redistribution of alpha-tubulin. These aggregates are also immunoreactive to ubiquitin, ubiquitin-conjugating enzyme, ER chaperone and proteasome subunits, demonstrating their aggresome-like properties. Furthermore, we show that the centrosomal aggregation of laforin and malin is dependent on the functional microtubule network. Laforin and malin form aggresome when expressed together or otherwise, suggesting that the two proteins are recruited to the centrosome independent of each other. Taken together, our results suggest that the centrosomal accumulation of malin, possibly with the help of laforin, may enhance the ubiquitination of its substrates and facilitate their efficient degradation by proteasome. Defects in malin or laforin may thus lead to increased levels of misfolded and/or target proteins, which may eventually affect the physiological processes of the neuron. Thus, defects in protein degradation and clearance are likely to be the primary trigger in the physiopathology of LD. PMID- 17337487 TI - A stitch in time. PMID- 17337486 TI - Exact moment of tendon of pectoralis major muscle rupture captured on video. AB - A powerlifting athlete ruptured his left tendon of the pectoralis major muscle while attempting to lift 160 kg in a Brazilian bench press championship. The injury seemed to occur in the concentric phase of exercise; however, the more common mechanism of rupture is during the eccentric phase. The tendon was reinserted to the humerus 3 weeks later with screws and washers. The athlete returned to competitive activities after 5 months. One year later he lifted 170 kg and won the national championship. PMID- 17337488 TI - Accuracy of the 5-day FreeStyle Navigator Continuous Glucose Monitoring System: comparison with frequent laboratory reference measurements. AB - OBJECTIVE: The purpose of this study was to compare the accuracy of measurements of glucose in interstitial fluid made with the FreeStyle Navigator Continuous Glucose Monitoring System with Yellow Springs Instrument laboratory reference measurements of venous blood glucose. RESEARCH DESIGN AND METHODS: Fifty-eight subjects with type 1 diabetes, aged 18-64 years, were enrolled in a multicenter, prospective, single-arm study. Each subject wore two sensors simultaneously, which were calibrated with capillary fingerstick measurements at 10, 12, 24, and 72 h after insertion. Measurements from the FreeStyle Navigator system were collected at 1-min intervals and compared with venous measurements taken once every 15 min for 50 h over the 5-day period of sensor wear in an in-patient clinical research center. Periods of high rates of change of glucose were induced by insulin and glucose challenges. RESULTS: Comparison of the FreeStyle Navigator measurements with the laboratory reference method (n = 20,362) gave mean and median absolute relative differences (ARDs) of 12.8 and 9.3%, respectively. The percentage in the clinically accurate Clarke error grid A zone was 81.7% and that in the in the benign error B zone was 16.7%. During low rates of change (< +/-1 mg x dl(-1) x min(-1)), the percentage in the A zone was higher (84.9%) and the mean and median ARDs were lower (11.7 and 8.5%, respectively). CONCLUSIONS: Measurements with the FreeStyle Navigator system were found to be consistent and accurate compared with venous measurements made using a laboratory reference method over 5 days of sensor wear (82.5% in the A zone on day 1 and 80.9% on day 5). PMID- 17337489 TI - Relationship of physician volume with process measures and outcomes in diabetes. AB - OBJECTIVE: The volume of patients cared for by an individual physician (physician volume) has been linked to improved outcomes for a number of conditions. It is not known whether a similar association exists for treatment of diabetes. In this study we aimed to determine whether physician volume is associated with improved process measures and outcomes in diabetes care. RESEARCH DESIGN AND METHODS: This retrospective cohort study analyzed electronic medical records data for 7,120 patients with diabetes treated by 368 primary care physicians at practices affiliated with two large academic hospitals. The associations between physician volume of diabetic patients (diabetes volume) and annual A1C and LDL testing, as well as blood pressure, A1C, and LDL levels, were evaluated. RESULTS: In multivariable analysis, absolute diabetes volume was linked to decreased odds of A1C testing (4% less for each additional patient seen; P = 0.05), and relative diabetes volume (fraction of the total patients seen who had diabetes) was associated with decreased odds of both A1C (25% less for every 10% increase in the number of diabetic patients seen annually; P = 0.03) and LDL testing (20% less for every 10% increase in the number of diabetic patients; P < 0.001). Physician volume was not significantly associated with the odds of blood pressure, A1C, or LDL control at the end of the study. CONCLUSIONS: Higher physician volume in care of diabetic patients is associated with decreased adherence to surveillance guidelines and no measurable difference in treatment outcomes. PMID- 17337490 TI - Maintenance of glucose control in patients with type 1 diabetes during acute mental stress by riding high-speed rollercoasters. PMID- 17337491 TI - Development of diabetes in Chinese with the metabolic syndrome: a 6-year prospective study. AB - OBJECTIVE: We investigated the association of the metabolic syndrome with new onset diabetes in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. RESEARCH DESIGN AND METHODS: We followed up on 1,679 subjects without diabetes at baseline. Those with a previous diagnosis of diabetes or those who were receiving drug treatment were considered to be diabetic. The remaining subjects underwent a 75-g oral glucose tolerance test (OGTT). Diabetes was defined by plasma glucose > or =7.0 mmol/l with fasting and/or > or =11.1 mmol/l at 2 h. RESULTS: The prevalences of the metabolic syndrome at baseline were 14.5 and 11.4%, respectively, according to U.S. National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. After a median of 6.4 years, there were 66 and 54 new cases of diabetes in men and women, respectively. The metabolic syndrome at baseline predicted incident diabetes. Hazard ratios (HRs) for the NCEP and IDF definitions of the syndrome were 4.1 [95% CI 2.8-6.0] and 3.5 [2.3-5.2], respectively. HRs for fasting plasma glucose (FPG) > or =6.1 or 5.6 mmol/l were 6.9 [4.1-11.5] and 4.1 [2.8-6.0], respectively. The NCEP and IDF criteria had 41.9 and 31.7% sensitivity and 87.5 and 90.2% specificity, respectively. Their positive predictive values were low, approximately 20%, but their negative predictive values were approximately 95%. CONCLUSIONS: The metabolic syndrome, particularly its component, elevated FPG, predicts diabetes in Chinese. An individual without the metabolic syndrome is unlikely to develop diabetes, but one who has it should practice therapeutic lifestyle changes and have periodic FPG measurements to detect new-onset diabetes. PMID- 17337492 TI - Impact of telmisartan versus ramipril on renal endothelial function in patients with hypertension and type 2 diabetes. AB - OBJECTIVE: One of the earliest signs of vascular change is endothelial dysfunction, which is also known to provoke albuminuria and to predict cardiovascular prognosis. The aim of this study was to analyze the effects of renin-angiotensin system (RAS) blockade on renal endothelial function. RESEARCH DESIGN AND METHODS: In a multicenter, prospective, double-blind, forced titration, randomized study, 96 patients with type 2 diabetes, hypertension, glomerular filtration rate >80 ml/min, and normo- or microalbuminuria were treated once daily with 40/80 mg telmisartan or 5/10 mg ramipril for 9 weeks. RESULTS: The mean +/- SE fall in renal plasma flow (RPF) in response to intravenous N(G)-monomethyl-L-arginine (L-NMMA), reflecting the magnitude of nitric oxide (NO) activity, increased with telmisartan from 71.9 +/- 9.0 ml/min before therapy to 105.2 +/- 9.7 ml/min at the end of treatment (P < 0.001). With ramipril, RPF response to L-NMMA increased from 60.1 +/- 12.2 to 87.8 +/- 9.2 ml/min (P = 0.018). The adjusted difference between treatments was -17.1 +/- 13.7 ml/min (P = 0.214). In accordance, telmisartan increased RPF at rest (i.e., without L-NMMA) from 652.0 +/- 27.0 to 696.1 +/- 31.0 ml/min (P = 0.047), whereas ramipril produced no significant changes in RPF. The more the basal NO activity improved, the greater was the vasodilatory effect on renal vasculature (r = 0.47, P < 0.001). CONCLUSIONS: In patients with type 2 diabetes, telmisartan and ramipril both increased NO activity of the renal endothelium significantly, which in turn may support the preservation of cardiovascular and renal function. PMID- 17337493 TI - Satisfaction and quality of life with premeal inhaled versus injected insulin in adolescents and adults with type 1 diabetes. AB - OBJECTIVE: We sought to compare and evaluate the impact of inhaled versus injected insulin on potential mediators of patient acceptance of insulin therapy while maintaining comparable A1C levels. RESEARCH DESIGN AND METHODS: During a noninferiority efficacy trial conducted in 40 centers in the U.S., we surveyed treatment satisfaction, quality of life, and adherence barriers at weeks -4, -1, 6, 12, 20, and 24 in adolescents aged 12-17 years and adults with type 1 diabetes who received premeal regular plus twice-daily NPH insulin during a 4-week run-in; then, subjects were randomized to premeal inhaled human insulin plus twice-daily NPH (adults, n = 102; adolescents, n = 60) (inhaled) or remaining on run-in therapy (n = 105 and 60, respectively) (subcutaneous injection). RESULTS: Overall treatment satisfaction (0-100) increased by 13.2 +/- 1.1 units for inhaled insulin (baseline = 63.3 +/- 1.2) compared with 1.7 +/- 0.8 for subcutaneous insulin injection (baseline = 64.1 +/- 1.2, P < 0.0001). All 12 satisfaction subscales favored inhaled insulin (all P < 0.01), and effects did not vary by age or sex. Despite similar baseline-adjusted end point A1C for inhaled (7.7 +/- 0.1%) and subcutaneous (7.9 +/- 0.1%) regimens, quality-of-life scales of mental health, symptoms, health status, cognitive functioning, and adherence barriers during treatment were more favorable for inhaled insulin (all P < 0.05). Greater satisfaction was associated with fewer barriers to insulin adherence (rho = 0.78, P < 0.0001) and a greater reduction in A1C (rho = -0.18, P < 0.001). CONCLUSIONS: Treatment satisfaction was substantially more favorable, adherence barriers moderately lower, and quality of life moderately higher for inhaled compared with subcutaneous regimen. It remains to be demonstrated whether these patient-reported outcomes will translate into improved adherence and glycemic control. PMID- 17337494 TI - Dipeptidyl peptidase-4 inhibitors: clinical data and clinical implications. PMID- 17337495 TI - Dipeptidyl peptidase-4 inhibition and the treatment of type 2 diabetes: preclinical biology and mechanisms of action. PMID- 17337496 TI - Digenic inheritance of hepatocyte nuclear factor-1alpha and -1beta with maturity onset diabetes of the young, polycystic thyroid, and urogenital malformations. PMID- 17337497 TI - How doctors choose medications to treat type 2 diabetes: a national survey of specialists and academic generalists. AB - OBJECTIVE: Glycemic control remains suboptimal despite the wide range of available medications. More effective medication prescription might result in better control. However, the process by which physicians choose glucose-lowering medicines is poorly understood. We sought to study the means by which physicians choose medications for type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We surveyed 886 physician members of either the Society of General Internal Medicine (academic generalists, response rate 30%) or the American Diabetes Association (specialists, response rate 23%) currently managing patients with type 2 diabetes. Respondents weighed the importance of 15 patient, physician, and nonclinical factors when deciding which medications to prescribe for type 2 diabetic subjects at each of three management stages (initiation, use of second line oral agents, and insulin). RESULTS: Respondents reported using a median of five major considerations (interquartile range 4-6) at each stage. Frequently cited major considerations included overall assessment of the patient's health/comorbidity, A1C level, and patient's adherence behavior but not expert guidelines/hospital algorithms or patient age. For insulin initiation, academic generalists placed greater emphasis on patient adherence (76 vs. 60% of specialists, P < 0.001). These generalists also identified patient fear of injections (68%) and patient desire to prolong noninsulin therapy (68%) as major insulin barriers. Overall, qualitative factors (e.g., adherence, motivation, overall health assessment) were somewhat more highly considered than quantitative factors (e.g., A1C, age, weight) with mean aggregate scores of 7.3 vs. 6.9 on a scale of 0-10, P < 0.001. CONCLUSIONS: The physicians in our survey considered a wide range of qualitative and quantitative factors when making medication choices for hyperglycemia management. The apparent complexity of the medication choice process contrasts with current evidence-based treatment guidelines. PMID- 17337498 TI - Noninvasive type 2 diabetes screening: superior sensitivity to fasting plasma glucose and A1C. AB - OBJECTIVE: This study compared the performance of a novel noninvasive technology to fasting plasma glucose (FPG) and A1C tests for detecting undiagnosed diabetes and impaired glucose tolerance. RESEARCH DESIGN AND METHODS: The design was a head-to-head evaluation in a naive population. Consented subjects received FPG and A1C tests and an oral glucose tolerance test (OGTT). Subjects were also measured by a noninvasive device that detects the fluorescence of skin advanced glycation end products. A total of 351 subjects participated. RESULTS: Subjects with 2-h OGTT values > or = 140 mg/dl defined the positive screening class. A total of 84 subjects (23.9% prevalence) screened positive. The performances of the noninvasive device, FPG, and A1C were evaluated for sensitivity and specificity against this classification. At the impaired fasting glucose threshold (FPG = 100 mg/dl), the FPG testing sensitivity was 58% and the specificity was 77.4%. At that same specificity, the sensitivity for A1C testing was 63.8%, while the noninvasive testing sensitivity was 74.7%. The sensitivity advantage of the noninvasive device over both blood tests for detecting diabetes and precursors was statistically significant (P < 0.05). CONCLUSIONS: The noninvasive technology showed clinical performance advantages over both FPG and A1C testing. The sensitivity differential indicated that the noninvasive device is capable of identifying 28.8% more individuals in the OGTT-defined positive screening class than FPG testing and 17.1% more than A1C testing. The combination of higher sensitivity and greater convenience--rapid results with no fasting or blood draws--makes the device well suited for opportunistic screening. PMID- 17337499 TI - Insulin resistance in liver cirrhosis is not associated with circulating retinol binding protein 4. AB - OBJECTIVE: Retinol-binding protein 4 (RBP4) has been identified as a novel adipokine mediating systemic insulin resistance, and elevated serum RBP4 indicates overt or impending insulin resistance in lean, obese, and type 2 diabetic subjects. As insulin resistance is present in nearly all patients with liver cirrhosis, we evaluated RBP4 in patients with chronic liver disease (CLD). RESEARCH DESIGN AND METHODS: Serum RBP4 was measured in 111 CLD patients. Ninety nine age- and sex-matched healthy blood donors served as control subjects. RBP4 gene expression was also quantified in normal and cirrhotic rat liver. RESULTS: In CLD patients, serum RBP4 was significantly reduced compared with healthy control subjects and closely correlated with the stage of liver cirrhosis. CLD patients without cirrhosis showed normal RBP4 concentrations, which correlated with serum glucose and insulin secretion and inversely correlated with insulin sensitivity. In patients with Child A-C liver cirrhosis, however, RBP4 was not correlated with glucose metabolism or other adipokines, such as adiponectin or resistin, but closely linked to the hepatic biosynthetic capacity, fibrotic changes in liver histology, or clinical complications such as portal hypertension. In an animal model of experimental cirrhosis, hepatic RBP4 gene expression decreased in cirrhotic liver. CONCLUSIONS: RBP4 appears, unlike in obesity or type 2 diabetes, not to be a relevant systemic factor in the pathogenesis of insulin resistance in liver cirrhosis. Liver function has a tremendous impact on RBP4 levels, and future studies will need to take liver function into account when examining serum RBP4 levels. PMID- 17337500 TI - Risk imparted by various parameters of smoking in Japanese men with type 2 diabetes on their development of microalbuminuria: analysis from the Tsukuba Kawai Diabetes Registry. PMID- 17337501 TI - A1C and survival in maintenance hemodialysis patients. AB - OBJECTIVE: The optimal target for glycemic control has not been established in diabetic dialysis patients. RESEARCH DESIGN AND METHODS: To address this question, the national database of a large dialysis organization (DaVita) was analyzed via time-dependent survival models with repeated measures. RESULTS: Of 82,933 patients undergoing maintenance hemodialysis (MHD) in DaVita outpatient clinics over 3 years (July 2001 through June 2004), 23,618 diabetic MHD patients had A1C measurements at least once. Unadjusted survival analyses indicated paradoxically lower death hazard ratios (HRs) with higher A1C values. However, after adjusting for potential confounders (demographics, dialysis vintage, dose, comorbidity, anemia, and surrogates of malnutrition and inflammation), higher A1C values were incrementally associated with higher death risks. Compared with A1C in the 5-6% range, the adjusted all-cause and cardiovascular death HRs for A1C > or = 10% were 1.41 (95% CI 1.25-1.60) and 1.73 (1.44-2.08), respectively (P < 0.001). The incremental increase in death risk for rising A1C values was monotonic and robust in nonanemic patients (hemoglobin > 11.0 g/dl). In subgroup analyses, the association between A1C > 6% and increased death risk was more prominent among younger patients, those who had undergone dialysis for > 2 years, and those with higher protein intake (> 1 g x kg(-1) x day(-1)), blood hemoglobin (> 11 g/dl), or serum ferritin values (> 500 ng/ml). CONCLUSIONS: In diabetic MHD patients, the apparently counterintuitive association between poor glycemic control and greater survival is explained by such confounders as malnutrition and anemia. All things equal, higher A1C is associated with increased death risk. Lower A1C levels not related to malnutrition or anemia appear to be associated with improved survival in MHD patients. PMID- 17337502 TI - Clustering of risk factors in parents of patients with type 1 diabetes and nephropathy. AB - OBJECTIVE: To assess the impact of parental risk factors for diabetic nephropathy. RESEARCH DESIGN AND METHODS: This cross-sectional study included 2,355 type 1 diabetic patients from the FinnDiane (Finnish Diabetic Nephropathy) study. Diabetic nephropathy was defined as macroalbuminuria (urinary albumin excretion rate >200 microg/min or >300 mg/24 h) or end-stage renal disease. Information was available from 4,676 parents. Parental scores were calculated based on the number of various traits in the parents. RESULTS: Patients with diabetic nephropathy, compared with those without diabetic nephropathy, had a higher prevalence of maternal (41 vs. 35%, P = 0.046) and parental (62 vs. 55%, P = 0.044) hypertension, maternal stroke (7.6 vs. 5.1%, P = 0.044), and maternal (1.4 vs. 0.7%, P = 0.058) and parental (4.3 vs. 2.9%, P = 0.030) type 1 diabetes. If both, compared with none, of the parents had hypertension, the adjusted odds ratio (OR) for diabetic nephropathy in offspring was 1.56 (95% CI 1.13-2.15). The adjusted OR for diabetic nephropathy was 2.13 (1.36-3.33) for the parental hypertension-diabetes score (3-4 vs. 0 points) and 2.13 (1.37-3.33) for the parental hypertension-cardiovascular disease (CVD)-diabetes score (4-6 vs. 0 points). Fathers of patients with diabetic nephropathy, compared with those without diabetic nephropathy, had reduced overall survival (log-rank P = 0.04) and reduced cardiovascular survival (log-rank P = 0.03). CONCLUSIONS: A cluster of parental hypertension, CVD, and diabetes is associated with diabetic nephropathy in type 1 diabetes, as is paternal mortality. PMID- 17337504 TI - Motivational interviewing improves weight loss in women with type 2 diabetes. AB - OBJECTIVE: We sought to determine whether adding motivational interviewing to a behavioral weight control program improves weight loss outcomes and glycemic control for overweight women with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a randomized, controlled, clinical trial in which participants all received an 18-month, group-based behavioral obesity treatment and were randomized to individual sessions of motivational interviewing or attention control (total of five sessions) as an adjunct to the weight control program. Overweight women with type 2 diabetes treated by oral medications who could walk for exercise were eligible. Primary outcomes were weight and A1C, assessed at 0, 6, 12, and 18 months. RESULTS: A total of 217 overweight women (38% African American) were randomized (93% retention rate). Women in motivational interviewing lost significantly more weight at 6 months (P = 0.01) and 18 months (P = 0.04). Increased weight losses with motivational interviewing were mediated by enhanced adherence to the behavioral weight control program. African-American women lost less weight than white women overall and appeared to have a diminished benefit from the addition of motivational interviewing. Significantly greater A1C reductions were observed in those undergoing motivational interviewing at 6 months (P = 0.02) but not at 18 months. CONCLUSIONS: Motivational interviewing can be a beneficial adjunct to behavioral obesity treatment for women with type 2 diabetes, although the benefits may not be sustained among African-American women. PMID- 17337503 TI - Glucose homeostasis and genotype-phenotype interplay in cystic fibrosis patients with CFTR gene deltaF508 mutation. AB - OBJECTIVE: We sought to determine the clinical phenotype of adolescent/adult patients with cystic fibrosis, according to heterozygosity or homozygosity for cystic fibrosis transmembrane regulator (CFTR) deltaF508 mutation, and to analyze their characteristics according to glucose tolerance status. RESEARCH DESIGN AND METHODS: A total of 76 cystic fibrosis patients with CFTR deltaF508 mutation (33 heterozygous and 43 homozygous) stratified according to normal glucose tolerance (NGT) (n = 51) or abnormal glucose homeostasis (AGH) (impaired fasting glucose, impaired glucose tolerance, or diabetes; n = 25) had their homeostasis model assessment (HOMA) of beta-cell function and of insulin sensitivity and hyperbolic product (beta-cell function x insulin sensitivity [B x S]) measured. Pancreatic exocrine insufficiency was inferred from pancreatine requirements. Clinical effects of insulin therapy on weight and lung function were recorded. RESULTS: AGH was observed in 24 and 40% of heterozygous and homozygous subjects, respectively. AGH patients were older than NGT patients (mean +/- SD age 29 +/- 10 vs. 23 +/- 8 years, P = 0.006), and their beta-cell function was lower (93 +/- 49 vs. 125 +/- 51%, P = 0.011). Insulin sensitivity values were comparable in NGT and AGH patients. A lower B x S product was observed in AGH, although it was nonsignificant when adjusted for error propagation. Pancreatic insufficiency was observed in 52 and 100% of heterozygous and homozygous patients (P = 0.001). CONCLUSIONS: Pre-diabetes and diabetes represent frequent comorbidities in CFTR deltaF508 mutation in the homozygous or heterozygous states. Impairment of insulin secretion, as shown by HOMA, is an important determinant when compared with the magnitude of compensation from insulin sensitivity. Given the high prevalence of abnormal glucose tolerance, screening for (pre-)diabetes is mandatory. Insulin supplementation in diabetic subjects with CFTR deltaF508 mutation seems a rational therapy for consideration, although this does not preclude that therapy directed toward insulin resistance could also interact. PMID- 17337505 TI - Sulfonylurea treatment in young children with neonatal diabetes: dealing with hyperglycemia, hypoglycemia, and sick days. PMID- 17337506 TI - Dysfunction of Golgi tethers, SNAREs, and SNAPs in monocrotaline-induced pulmonary hypertension. AB - Monocrotaline (MCT)-induced pulmonary hypertension (PH) in the rat is a widely used experimental model. We have previously shown that MCT pyrrole (MCTP) produces loss of caveolin-1 (cav-1) and endothelial nitric oxide synthase from plasma membrane raft microdomains in pulmonary arterial endothelial cells (PAEC) with the trapping of these proteins in the Golgi organelle (the Golgi blockade hypothesis). In the present study, we investigated the mechanisms underlying this intracellular trafficking block in experiments in cell culture and in the MCT treated rat. In cell culture, PAEC showed trapping of cav-1 in Golgi membranes as early as 6 h after exposure to MCTP. Phenotypic megalocytosis and a reduction in anterograde trafficking (assayed in terms of the secretion of horseradish peroxidase derived from exogenously transfected expression constructs) were evident within 12 h after MCTP. Cell fractionation and immunofluorescence techniques revealed the marked accumulation of diverse Golgi tethers, soluble N ethylmaleimide-sensitive factor (NSF) attachment protein receptors (SNAREs), and soluble NSF attachment proteins (SNAPs), which mediate membrane fusion during vesicular trafficking (GM130, p115, giantin, golgin 84, clathrin heavy chain, syntaxin-4, -6, Vti1a, Vti1b, GS15, GS27, GS28, SNAP23, and alpha-SNAP) in the enlarged/circumnuclear Golgi in MCTP-treated PAEC and A549 lung epithelial cells. Moreover, NSF, an ATPase required for the "disassembly" of SNARE complexes subsequent to membrane fusion, was increasingly sequestered in non-Golgi membranes. Immunofluorescence studies of lung tissue from MCT-treated rats confirmed enlargement of perinuclear Golgi elements in lung arterial endothelial and parenchymal cells as early as 4 days after MCT. Thus MCT-induced PH represents a disease state characterized by dysfunction of Golgi tethers, SNAREs, and SNAPs and of intracellular vesicular trafficking. PMID- 17337507 TI - Modulation of pulmonary endothelial endothelin B receptor expression and signaling: implications for experimental hepatopulmonary syndrome. AB - The hepatopulmonary syndrome (HPS) results from intrapulmonary vasodilation in the setting of cirrhosis and portal hypertension. In experimental HPS, pulmonary endothelial endothelin B (ET(B)) receptor overexpression and increased circulating endothelin-1 (ET-1) contribute to vasodilation through enhanced endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. In both experimental cirrhosis and prehepatic portal hypertension, ET(B) receptor overexpression correlates with increased vascular shear stress, a known modulator of ET(B) receptor expression. We investigated the mechanisms of pulmonary endothelial ET(B) receptor-mediated eNOS activation by ET-1 in vitro and in vivo. The effect of shear stress on ET(B) receptor expression was assessed in rat pulmonary microvascular endothelial cells (RPMVECs). The consequences of ET(B) receptor overexpression on ET-1-dependent ET(B) receptor-mediated eNOS activation were evaluated in RPMVECs and in prehepatic portal hypertensive animals exposed to exogenous ET-1. Laminar shear stress increased ET(B) receptor expression in RPMVECs without altering mRNA stability. Both shear-mediated and targeted overexpression of the ET(B) receptor enhanced ET-1-mediated ET(B) receptor dependent eNOS activation in RPMVECs through Ca(2+)-mediated signaling pathways and independent of Akt activation. In prehepatic portal hypertensive animals relative to control, ET-1 administration also activated eNOS independent of Akt activation and triggered HPS. These findings support that increased pulmonary microvascular endothelial ET(B) receptor expression modulates ET-1-mediated eNOS activation, independent of Akt, and contributes to the development of HPS. PMID- 17337508 TI - Heat shock protein 90 modulates endothelial nitric oxide synthase activity and vascular reactivity in the newborn piglet pulmonary circulation. AB - Heat shock protein 90 (Hsp90) binding to endothelial nitric oxide synthase (eNOS) is an important step in eNOS activation. The conformational state of bound Hsp90 determines whether eNOS produces nitric oxide (NO) or superoxide (O(2)(*-)). We determined the effects of the Hsp90 antagonists geldanamycin (GA) and radicicol (RA) on basal and ACh-stimulated changes in vessel diameter, cGMP production, and Hsp90:eNOS coimmunoprecipitation in piglet resistance level pulmonary arteries (PRA). In perfused piglet lungs, we evaluated the effects of GA and RA on ACh stimulated changes in pulmonary arterial pressure (Ppa) and perfusate accumulation of stable NO metabolites (NOx(-)). The effects of GA and RA on ACh stimulated O(2)(*-) generation was investigated in cultured pulmonary microvascular endothelial cells (PMVEC) by dihydroethidine (DHE) oxidation and confocal microscopy. Hsp90 inhibition with GA or RA reduced ACh-mediated dilation, abolished the ACh-stimulated increase in cGMP, and reduced eNOS:Hsp90 coprecipitation. GA and RA also inhibited the ACh-mediated changes in Ppa and NOx(-) accumulation rates in perfused lungs. ACh increased the rate of DHE oxidation in PMVEC pretreated with GA and RA but not in untreated cells. The cell permeable superoxide dismutase mimetic M40401 reversed GA-mediated inhibition of ACh-induced dilation in PRA. We conclude that Hsp90 is a modulator of eNOS activity and vascular reactivity in the newborn piglet pulmonary circulation. Uncoupling of eNOS with GA or RA inhibits ACh-mediated dilation by a mechanism that involves O(2)(*-) generation. PMID- 17337509 TI - Developmental regulation of DUOX1 expression and function in human fetal lung epithelial cells. AB - The purpose of this study was to determine the expression and cellular functions of the epithelial NADPH oxidase DUOX1 during alveolar type II cell development. When human fetal lung cells (gestational age 11-22 wk) were cultured to confluency on permeable filters, exposure of cells to a hormone mixture (dexamethasone, 8-Br-cAMP, and IBMX, together referred to as DCI) resulted in differentiation of cells into a mature type II phenotype as assessed by expression of lamellar bodies, surfactant proteins, and transepithelial electrical parameters. After 6 days in culture in presence of DCI, transepithelial resistance (2,616 +/- 529 Omega.cm(2)) and potential (-8.5 +/- 0.6 mV) indicated epithelial polarization. At the same time, treatment with DCI significantly increased the mRNA expression of DUOX1 ( approximately 21-fold), its maturation factor DUOXA1 ( approximately 12-fold), as well as DUOX protein ( approximately 12-fold), which was localized near the apical cell pole in confluent cultures. For comparison, in fetal lung specimens, DUOX protein was not detectable at up to 27 wk of gestational age but was strongly upregulated after 32 wk. Function of DUOX1 was assessed by measuring H(2)O(2) and acid production. Rates of H(2)O(2) production were increased by DCI treatment and blocked by small interfering RNA directed against DUOX1 or by diphenylene iodonium. DCI-treated cultures also showed increased intracellular acid production and acid release into the mucosal medium, and acid production was largely blocked by knockdown of DUOX1 mRNA. These data establish the regulated expression of DUOX1 during alveolar maturation, and indicate DUOX1 in alveolar H(2)O(2) and acid secretion by differentiated type II cells. PMID- 17337510 TI - Triclosan resistance in methicillin-resistant Staphylococcus aureus expressed as small colony variants: a novel mode of evasion of susceptibility to antiseptics. AB - OBJECTIVES: Triclosan is in widespread use in domestic, commercial and healthcare settings and is used to reduce methicillin-resistant Staphylococcus aureus (MRSA) load in carriers. Triclosan resistance is uncommon, usually being due to mutation in fabI or overexpression of efflux pumps. This study investigated the ability of triclosan-containing silicone elastomer to kill MRSA adherent to its surface. METHODS: Silicone discs containing triclosan were prepared by a matrix-expansion method previously described. Discs were exposed to three strains of MRSA for 1 h for adhesion to take place. After incubation, discs were removed at intervals, sonicated and the sonicates analysed by chemiluminescence and viable counting. Survivors were found to consist of small colony variants (SCVs). These were then subjected to tests for known SCV characteristics and for susceptibility to triclosan. RESULTS: Viable counts fell until 51 h, when they began to increase, due to SCV. Of the three SCV strains, two showed impaired coagulase production and all showed reduced deoxyribonuclease production. None was auxotrophic. MICs of triclosan in the SCV rose by between 8- and 67-fold. CONCLUSIONS: Prolonged exposure of MRSA to triclosan-impregnated silicone, as in 'antimicrobial' plastics or catheters, resulted in the induction of SCV status and triclosan resistance. This has implications for industrial, medical and domestic use of polymers containing triclosan. SCVs are pathogenic and persistent. The widespread use of triclosan could lead to infection with MRSA SCVs, and new antimicrobials with physiological targets similar to that of triclosan might give rise to SCV resistance in clinical use. PMID- 17337511 TI - Low sale of antibiotics without prescription: a cross-sectional study in Zimbabwean private pharmacies. AB - OBJECTIVES: To assess the quality of private pharmacy practice with a focus on the extent of antibiotic sales without prescription in private pharmacies in four Zimbabwean cities in relation to two tracer infectious conditions-sexually transmitted infections (STIs) among females and males, and diarrhoea in a child. METHODS: A cross-sectional study including pharmacies in Harare and three other towns. Information about each pharmacy was collected through structured interviews. Staff were interviewed using a different structured interview guide and simulated clients were used to assess staff performance. Data were analysed statistically, and step models to evaluate pharmacist performance were developed. RESULTS: A majority (69%) stated that they would never sell an antibiotic without a prescription and very few actually did in spite of a high patient demand. Few respondents however performed acceptably regarding provision of information and advice in relation to guidelines: 8% for the STI male, 33% for the STI female and 22% for the diarrhoea scenario. CONCLUSIONS: The study revealed low sales of antibiotics without prescription, showing good adherence to the letter of the law. However, few respondents performed acceptably in relation to guidelines when considering information and advice for the tracer conditions. PMID- 17337512 TI - Antimalarial efficacy and drug interactions of the novel semi-synthetic endoperoxide artemisone in vitro and in vivo. AB - OBJECTIVES: The in vitro and in vivo efficacy and drug-drug interactions of the novel semi-synthetic endoperoxide artemisone with standard antimalarials were investigated in order to provide the basis for the selection of the best partner drug. METHODS: Antimalarial activity and drug interactions were evaluated in vitro against Plasmodium falciparum by the incorporation of [(3)H]hypoxanthine. In vivo efficacy and drug interactions were assessed using the standard 4-day Peters' test. RESULTS: Artemisone was 10 times more potent than artesunate in vitro against a panel of 12 P. falciparum strains, independent of their susceptibility profile to antimalarial drugs, and consistently 4 to 10 times more potent than artesunate in rodent models against drug-susceptible and primaquine- or sulfadoxine/pyrimethamine-resistant Plasmodium berghei lines and chloroquine- or artemisinin-resistant lines of Plasmodium yoelii. Slight antagonistic trends were found between artemisone and chloroquine, amodiaquine, tafenoquine, atovaquone or pyrimethamine and additive to slight synergistic trends with artemisone and mefloquine, lumefantrine or quinine. Various degrees of synergy were observed in vivo between artemisone and mefloquine, chloroquine or clindamycin. CONCLUSIONS: These results confirm the increased efficacy of artemisone over artesunate against multidrug-resistant P. falciparum and provide the basis for the selection of potential partner drugs for future deployment in areas of multidrug-resistant malaria. Artemisone represents an important addition to the repertoire of artemisinin combination therapies currently in use, as it has enhanced antimalarial activity, improved bioavailability and stability over current endoperoxides. PMID- 17337513 TI - Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide. AB - OBJECTIVES: Clostridium difficile-associated disease has increased in incidence and severity. Recommended treatments include metronidazole and vancomycin. Recent investigations, however, document the failure of metronidazole to cure a substantial proportion of patients with Clostridium difficile colitis, but oral administration of vancomycin raises concerns over selection of antibiotic resistant organisms in the hospital environment. We have recently shown that nitazoxanide is as effective as metronidazole in initial therapy for C. difficile colitis. We hypothesized that this drug might be effective in treating patients who fail therapy with metronidazole. METHODS: In the present study, we identified 35 patients who failed treatment with metronidazole for C. difficile colitis; failure was defined as either no improvement in symptoms or signs of disease (28 patients) after >or= 14 days of treatment with metronidazole or prompt recurrence on at least two occasions after initially responding to such treatment (seven patients). These patients were ill with numerous co-morbidities. Nitazoxanide, 500 mg twice daily, was given for 10 days; results from all patients are included. RESULTS: Twenty-six (74%) of 35 patients responded to nitazoxanide, of whom seven later had recurrent disease, yielding a cure rate of 19 of 35 (54%) from initial therapy. Three who initially failed and one who had recurrent disease were re-treated with, and responded to, nitazoxanide. Thus, the aggregate cure with nitazoxanide in this difficult-to-treat population was 23 of 35 (66%). CONCLUSIONS: Nitazoxanide appears to provide effective therapy for patients with C. difficile colitis who fail treatment with metronidazole. PMID- 17337514 TI - Three cases of multiple thymoma with a review of the literature. AB - Three cases of patients with synchronous multiple thymoma are reported. Two patients had two thymomas each and the remaining patient had three. The thymomas in each patient all displayed similar histological findings, of which the WHO histological classification were type B2, A and B1, respectively. With a modified Masaoka staging system, the thymomas were determined to be stages II-1 and I in patient 1, one of stage III and two of stage I in patient 2, and two of stage II 1 in patient 3. We reviewed nine reported cases of multiple thymoma in which histological findings were provided and discuss whether they developed from multi centric origin or from intra-thymic metastasis. PMID- 17337515 TI - Total pelvic exenteration with sacrectomy for re-recurrence of rectal cancer. PMID- 17337516 TI - Comparison of time trends in cancer incidence (1973-1997) in East Asia, Europe and USA, from Cancer Incidence in Five Continents Vol. IV-VIII. PMID- 17337517 TI - Team climate for innovation: what difference does it make in general practice? AB - OBJECTIVE: Teamwork in primary healthcare is associated with patient care processes and staff outcomes. The ability of teams to be innovative is a hypothesized mechanism. We examined the characteristics of general practices with good team climate for innovation, and assessed the impact of climate on chronically ill patients' assessment of their care and on the job satisfaction of the staff. DESIGN: Large cross-sectional study. SETTING: Australian general practices. PARTICIPANTS: A total of 654 general practitioners and staff and 7505 chronically ill patients from 93 general practices in 6 Australian states and territories. MEASURES: The Team Climate Inventory and the Overall Job Satisfaction Scale, customized for use with general practices, were administered to general practitioners and practice staff, and the General Practice Assessment Survey was administered to patients. Practice characteristics were collected by survey from the principal doctor or practice manager. RESULTS: Mean scores of team climate in Australian general practices were similar to those reported in the UK, except that in our study there was no association between the number of doctors in a practice and their team climate. Better team climate was found in practices with fewer non-clinical staff. Team climate predicted the job satisfaction of the general practitioners and staff, irrespective of the number of practice staff. Better team climate was associated with greater satisfaction by patients with their care. CONCLUSIONS: Team climate is important for patient and staff satisfaction. In large general practices, separate sub-cultures may exist between administrative and clinical staff, which has implications for designing effective team interventions. PMID- 17337518 TI - Understanding what works--and why--in quality improvement: the need for theory driven evaluation. PMID- 17337519 TI - How is quality being monitored in Australian residential aged care facilities? A narrative review. AB - BACKGROUND: 'Quality of Care' is a difficult concept to measure, particularly within the context of residential aged care, which involves lifestyle issues as much as health issues. Recent years have seen an increased focus on quality within residential aged care. Yet, Australia does not have a structured and comprehensive quality monitoring system within this sector. PROBLEM: While the Australian Accreditation Standards have been credited with contributing to improving care since their introduction in 1998, they are only considered to represent minimum (rather than optimal) standards of quality, and they do not sufficiently focus on clinical outcomes. Further, individual facilities might only be assessed against these standards every 3 years; within that time, there is much scope for quality variations to go unnoticed. IMPLICATIONS: This paper contends that collecting and analysing comprehensive clinical data from aged care facility residents constitutes an essential step in the process of monitoring quality in this environment. Such data can be used to formulate indicators of quality, that is, to create markers to highlight areas of clinical care that might be of questionable (or exceptional) quality, enabling more detailed investigations of care practices within a facility. CONCLUSIONS: The above processes could thus fill the current gap in quality monitoring that exists within the Australian residential aged care system, thus ensuring the provision of best-practice care to this vulnerable population. PMID- 17337520 TI - Analysis of protein-linked glycosylation in a sperm-somatic cell adhesion system. AB - Murine sperm initiate fertilization by binding to the specialized extracellular matrix of their complementary eggs, known as the zona pellucida. On the basis of data reported in this study, mouse sperm also bind to rabbit erythrocytes with higher affinity than they do to murine eggs. This unusual interaction between a germ cell and a somatic cell ("sperm-somatic cell adhesion system") is also carbohydrate dependent based on its sensitivity to mild periodate oxidation. To determine what types of carbohydrate sequences could be involved in this interaction, the protein-linked oligosaccharides of rabbit erythrocytes were sequenced using novel matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry methods that enabled the analysis of individual components up to m/z 9000. The N-glycans are primarily complex biantennary and triantennary types terminated with Galalpha1-3Gal sequences. The majority of these oligosaccharides also possess one antenna consisting of a highly branched polylactosamine-type sequence that is also associated with many glycosphingolipids that coat rabbit erythrocytes. These erythrocytes also express Core 1 and Core 2 O-glycans terminated primarily with Galalpha1-3Gal sequences and to a lesser extent sialic acid. These results confirm that rabbit erythrocytes and mouse eggs present very different types of carbohydrate sequences on their surfaces. However, oligosaccharides terminated with beta1-6 linked N-acetyllactosamine or its alpha1-3 galactosylated analog are expressed on both the mouse zona pellucida and this somatic cell type. The far more abundant presentation of such sequences on rabbit erythrocytes compared with murine eggs could explain why mouse sperm display such exceptional affinity for this somatic cell type. PMID- 17337521 TI - Characterization of lipid rafts from Medicago truncatula root plasma membranes: a proteomic study reveals the presence of a raft-associated redox system. AB - Several studies have provided new insights into the role of sphingolipid/sterol rich domains so-called lipid rafts of the plasma membrane (PM) from mammalian cells, and more recently from leaves, cell cultures, and seedlings of higher plants. Here we show that lipid raft domains, defined as Triton X-100-insoluble membranes, can also be prepared from Medicago truncatula root PMs. These domains have been extensively characterized by ultrastructural studies as well as by analysis of their content in lipids and proteins. M. truncatula lipid domains are shown to be enriched in sphingolipids and Delta(7)-sterols, with spinasterol as the major compound, but also in steryl glycosides and acyl-steryl glycosides. A large number of proteins (i.e. 270) have been identified. Among them, receptor kinases and proteins related to signaling, cellular trafficking, and cell wall functioning were well represented whereas those involved in transport and metabolism were poorly represented. Evidence is also given for the presence of a complete PM redox system in the lipid rafts. PMID- 17337522 TI - Coordinate regulation of phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase by light and CO2 during C4 photosynthesis. AB - The aim of this study was to investigate the relationship between the phosphorylation and activation states of phosphoenolpyruvate carboxykinase (PEPCK) and to investigate how the phosphorylation states of PEPCK and phosphoenolpyruvate carboxylase (PEPC) are coordinated in response to light intensity and CO(2) concentration during photosynthesis in leaves of the C(4) plant Guinea grass (Panicum maximum). There was a linear, reciprocal relationship between the phosphorylation state of PEPCK and its activation state, determined in a selective assay that distinguishes phosphorylated from nonphosphorylated forms of the enzyme. At high photon flux density and high CO(2) (750 microL L( 1)), PEPC was maximally phosphorylated and PEPCK maximally dephosphorylated within 1 h of illumination. The phosphorylation state of both enzymes did not saturate until high light intensities (about 1,400 micromol quanta m(-2) s(-1)) were reached. After illumination at lower light intensities and CO(2) concentrations, the overall change in phosphorylation state was smaller and it took longer for the change in phosphorylation state to occur. Phosphorylation states of PEPC and PEPCK showed a strikingly similar, but inverse, pattern in relation to changes in light and CO(2). The protein phosphatase inhibitor, okadaic acid, promoted the phosphorylation of both enzymes. The protein synthesis inhibitor, cycloheximide, blocked dark phosphorylation of PEPCK. The data show that PEPC and PEPCK phosphorylation states are closely coordinated in vivo, despite being located in the mesophyll and bundle sheath cells, respectively. PMID- 17337525 TI - PlanTAPDB, a phylogeny-based resource of plant transcription-associated proteins. AB - Diversification of transcription-associated protein (TAP) families during land plant evolution is a key process yielding increased complexity of plant life. Understanding the evolutionary relationships between these genes is crucial to gain insight into plant evolution. We have determined a substantial set of TAPs that are focused on, but not limited to, land plants using PSI-BLAST searches and subsequent filtering and clustering steps. Phylogenies were created in an automated way using a combination of distance and maximum likelihood methods. Comparison of the data to previously published work confirmed their accuracy and usefulness for the majority of gene families. Evidence is presented that the flowering plant apical stem cell regulator WUSCHEL evolved from an ancestral homeobox gene that was already present after the water-to-land transition. The presence of distinct expanded gene families, such as COP1 and HIT in moss, is discussed within the evolutionary backdrop. Comparative analyses revealed that almost all angiosperm transcription factor families were already present in the earliest land plants, whereas many are missing among unicellular algae. A global analysis not only of transcription factors but also of transcriptional regulators and novel putative families is presented. A wealth of data about plant TAP families and all data accrued throughout their automated detection and analysis are made available via the PlanTAPDB Web interface. Evolutionary relationships of these genes are readily accessible to the nonexpert at a mouse-click. Initial analyses of selected gene families revealed that PlanTAPDB can easily be exerted for knowledge discovery. PMID- 17337526 TI - An unusual posttranscriptional processing in two betaine aldehyde dehydrogenase loci of cereal crops directed by short, direct repeats in response to stress conditions. AB - Various abilities to synthesize and accumulate glycine betaine (GB) are crucial for angiosperms to develop salt and drought tolerances. In higher plants, GB is synthesized by a two-step oxidation of choline via an intermediate form of betaine aldehyde, and catalyzed by choline monooxygenase and betaine aldehyde dehydrogenase (BADH). In this study, numerous truncated and/or recombinant transcripts of two BADH homologs resulting from an unusual posttranscriptional processing were detected in rice (Oryza sativa) and other cereal crops, including maize (Zea mays), wheat (Triticum aestivum), and barley (Hordeum vulgare). The observed events took place at the 5' exonic region, and led to the insertion of exogenous gene sequences and a variety of deletions that resulted in the removal of translation initiation codon, loss of functional domain, and frame-shifts with premature termination by introducing stop codon. By contrast, the BADH transcripts from dicotyledonous species, such as spinach (Spinacia oleracea), Arabidopsis (Arabidopsis thaliana), and tomato (Solanum lycopersicum), had correctly processed mRNA. This suggests the differentiation of posttranscriptional processing in BADH genes potentially contributes to the variation of GB-synthesizing capacities among various plant species. In addition, comprehensive sequence analyses demonstrated that extensive sequence similarities (named as short, direct repeats) are of paired presence surrounding the junctions of both the deletion and/or insertion sites in the unusual BADH transcripts. The site selection for the deletion/insertion was altered in response to the stress conditions. This indicates that the sequence elements of short, direct repeats are probably required for the recognition of the deletion/insertion sites. PMID- 17337527 TI - Actin dynamics in papilla cells of Brassica rapa during self- and cross pollination. AB - The self-incompatibility system of the plant species Brassica is controlled by the S-locus, which contains S-RECEPTOR KINASE (SRK) and S-LOCUS PROTEIN11 (SP11). SP11 binding to SRK induces SRK autophosphorylation and initiates a signaling cascade leading to the rejection of self pollen. However, the mechanism controlling hydration and germination arrest during self-pollination is unclear. In this study, we examined the role of actin, a key cytoskeletal component regulating the transport system for hydration and germination in the papilla cell during pollination. Using rhodamine-phalloidin staining, we showed that cross pollination induced actin polymerization, whereas self-pollination induced actin reorganization and likely depolymerization. By monitoring transiently expressed green fluorescent protein fused to the actin-binding domain of mouse talin, we observed the concentration of actin bundles at the cross-pollen attachment site and actin reorganization and likely depolymerization at the self-pollen attachment site; the results correspond to those obtained by rhodamine-phalloidin staining. We further showed that the coat of self pollen is sufficient to mediate this response. The actin-depolymerizing drug cytochalasin D significantly inhibited pollen hydration and germination during cross-pollination, further emphasizing a role for actin in these processes. Additionally, three-dimensional electron microscopic tomography revealed the close association of the actin cytoskeleton with an apical vacuole network. Self-pollination disrupted the vacuole network, whereas cross-pollination led to vacuolar rearrangements toward the site of pollen attachment. Taken together, our data suggest that self- and cross-pollination differentially affect the dynamics of the actin cytoskeleton, leading to changes in vacuolar structure associated with hydration and germination. PMID- 17337528 TI - Auxin synthesis-encoding transgene enhances grape fecundity. AB - Grape (Vitis vinifera) yield is largely dependent on the fecundity of the cultivar. The average number of inflorescences per shoot (i.e. shoot fruitfulness) is a trait related to fecundity of each grapevine. Berry number and weight per bunch are other features affecting grape yield. An ovule-specific auxin-synthesizing (DefH9-iaaM) transgene that increases the indole-3-acetic acid content of grape transgenic berries was transformed into cultivars Silcora and Thompson Seedless, which differ in the average number of inflorescences per shoots. Thompson Seedless naturally has very low shoot fruitfulness, whereas Silcora has medium shoot fruitfulness. The average number of inflorescences per shoot in DefH9-iaaM Thompson Seedless was doubled compared to its wild-type control. Berry number per bunch was increased in both transgenic cultivars. The quality and nutritional value of transgenic berries were substantially equivalent to their control fruits. The data presented indicate that auxin enhances fecundity in grapes, thus enabling to increase yield with lower production costs. PMID- 17337529 TI - Molecular modeling and site-directed mutagenesis reveal the benzylisoquinoline binding site of the short-chain dehydrogenase/reductase salutaridine reductase. AB - Recently, the NADPH-dependent short-chain dehydrogenase/reductase (SDR) salutaridine reductase (E.C. 1.1.1.248) implicated in morphine biosynthesis was cloned from Papaver somniferum. In this report, a homology model of the Papaver bracteatum homolog was created based on the x-ray structure of human carbonyl reductase 1. The model shows the typical alpha/beta-folding pattern of SDRs, including the four additional helices alphaF'-1 to alphaF'-4 assumed to prevent the dimerization of the monomeric short-chain dehydrogenases/reductases. Site directed mutagenesis of asparagine-152, serine-180, tyrosine-236, and lysine-240 resulted in enzyme variants with strongly reduced performance or inactive enzymes, showing the involvement of these residues in the proton transfer system for the reduction of salutaridine. The strong preference for NADPH over NADH could be abolished by replacement of arginine residues 44 and 48 by glutamic acid, confirming the interaction between the arginines and the 2'-phosphate group. Docking of salutaridine into the active site revealed nine amino acids presumably responsible for the high substrate specificity of salutaridine reductase. Some of these residues are arranged in the right position by an additional alphaE' helix, which is not present in SDRs analyzed so far. Enzyme kinetic data from mutagenic replacement emphasize the critical role of these residues in salutaridine binding and provide the first data on the molecular interaction of benzylisoquinoline alkaloids with enzymes. PMID- 17337530 TI - Iron acquisition by phytosiderophores contributes to cadmium tolerance. AB - Based on the ability of phytosiderophores to chelate other heavy metals besides iron (Fe), phytosiderophores were suggested to prevent graminaceous plants from cadmium (Cd) toxicity. To assess interactions between Cd and phytosiderophore mediated Fe acquisition, maize (Zea mays) plants were grown hydroponically under limiting Fe supply. Exposure to Cd decreased uptake rates of 59Fe(III) phytosiderophores and enhanced the expression of the Fe-phytosiderophore transporter gene ZmYS1 in roots as well as the release of the phytosiderophore 2' deoxymugineic acid (DMA) from roots under Fe deficiency. However, DMA hardly mobilized Cd from soil or from a Cd-loaded resin in comparison to the synthetic chelators diaminetriaminepentaacetic acid and HEDTA. While nano-electrospray-high resolution mass spectrometry revealed the formation of an intact Cd(II)-DMA complex in aqueous solutions, competition studies with Fe(III) and zinc(II) showed that the formed Cd(II)-DMA complex was weak. Unlike HEDTA, DMA did not protect yeast (Saccharomyces cerevisiae) cells from Cd toxicity but improved yeast growth in the presence of Cd when yeast cells expressed ZmYS1. When supplied with Fe-DMA as a Fe source, transgenic Arabidopsis (Arabidopsis thaliana) plants expressing a cauliflower mosaic virus 35S-ZmYS1 gene construct showed less growth depression than wild-type plants in response to Cd. These results indicate that inhibition of ZmYS1-mediated Fe-DMA transport by Cd is not related to Cd-DMA complex formation and that Cd-induced phytosiderophore release cannot protect maize plants from Cd toxicity. Instead, phytosiderophore-mediated Fe acquisition can improve Fe uptake in the presence of Cd and thereby provides an advantage under Cd stress relative to Fe acquisition via ferrous Fe. PMID- 17337531 TI - Regulation of NH4+ transport by essential cross talk between AMT monomers through the carboxyl tails. AB - Ammonium transport across plant plasma membranes is facilitated by AMT/Rh-type ammonium transporters (AMTs), which also have homologs in most organisms. In the roots of the plant Arabidopsis (Arabidopsis thaliana), AMTs have been identified that function directly in the high-affinity NH4+ acquisition from soil. Here, we show that AtAMT1;2 has a distinct role, as it is located in the plasma membrane of the root endodermis. AtAMT1;2 functions as a comparatively low-affinity NH4+ transporter. Mutations at the highly conserved carboxyl terminus (C terminus) of AMTs, including one that mimics phosphorylation at a putative phosphorylation site, impair NH4+ transport activity. Coexpressing these mutants along with wild type AtAMT1;2 substantially reduced the activity of the wild-type transporter. A molecular model of AtAMT1;2 provides a plausible explanation for the dominant inhibition, as the C terminus of one monomer directly contacts the neighboring subunit. It is suggested that part of the cytoplasmic C terminus of a single monomer can gate the AMT trimer. This regulatory mechanism for rapid and efficient inactivation of NH4+ transporters may apply to several AMT members to prevent excess influx of cytotoxic ammonium. PMID- 17337532 TI - Actin is involved in auxin-dependent patterning. AB - Polar transport of auxin has been identified as a central element of pattern formation. The polarity of auxin transport is linked to the cycling of pin-formed proteins, a process that is related to actomyosin-dependent vesicle traffic. To get insight into the role of actin for auxin transport, we used patterned cell division to monitor the polarity of auxin fluxes. We show that cell division in the tobacco (Nicotiana tabacum L. cv Bright-Yellow 2) cell line is partially synchronized and that this synchrony can be perturbed by inhibition of auxin transport by 1-N-naphthylphthalamic acid. To address the role of actin in this synchrony, we induced a bundled configuration of actin by overexpressing mouse talin. The bundling of actin impairs the synchrony of cell division and increases the sensitivity to 1-N-naphthylphthalamic acid. Addition of the polarly transported auxins indole-3-acetic acid and 1-naphthyl acetic acid (but not 2,4 dichlorophenoxyacetic acid) restored both the normal organization of actin and the synchrony of cell division. This study suggests that auxin controls its own transport by changing the state of actin filaments. PMID- 17337533 TI - The redox imbalanced mutants of Arabidopsis differentiate signaling pathways for redox regulation of chloroplast antioxidant enzymes. AB - A network of enzymatic and nonenzymatic antioxidants protects chloroplasts from photooxidative damage. With all enzymatic components being nuclear encoded, the control of the antioxidant capacity depends on chloroplast-to-nucleus redox signaling. Using an Arabidopsis (Arabidopsis thaliana) reporter gene line expressing luciferase under control of the redox-sensitive 2-cysteine peroxiredoxin A (2CPA) promoter, six mutants with low 2CPA promoter activity were isolated, of which five mutants show limitations in redox-box regulation of the 2CPA promoter. In addition to 2CPA, the transcript levels for other chloroplast antioxidant enzymes were decreased, although a higher oxidation status of the ascorbate pool, a higher reduction state of the plastoquinone pool, and an increased oxidation status of the 2-Cys peroxiredoxin pool demonstrated photooxidative stress conditions. Greening of the mutants, chloroplast ultrastructure, steady-state photosynthesis, and the responses to the stress hormone abscisic acid were wild type like. In the rosette state, the mutants were more sensitive to low CO2 and to hydrogen peroxide. Comparison of gene expression patterns and stress sensitivity characterizes the mutants as redox imbalanced in the regulation of nuclear-encoded chloroplast antioxidant enzymes and differentiates redox signaling cascades. PMID- 17337534 TI - Participation of endomembrane cation/H+ exchanger AtCHX20 in osmoregulation of guard cells. AB - Guard cell movement is induced by environmental and hormonal signals that cause changes in turgor through changes in uptake or release of solutes and water. Several transporters mediating these fluxes at the plasma membrane have been characterized; however, less is known about transport at endomembranes. CHX20, a member of a poorly understood cation/H+ exchanger gene family in Arabidopsis (Arabidopsis thaliana), is preferentially and highly expressed in guard cells as shown by promoterbeta-glucuronidase activity and by whole-genome microarray. Interestingly, three independent homozygous mutants carrying T-DNA insertions in CHX20 showed 35% reduction in light-induced stomatal opening compared to wild type plants. To test the biochemical function of CHX20, cDNA was expressed in a yeast (Saccharomyces cerevisiae) mutant that lacks Na+(K+)/H+ antiporters (Deltanhx1 Deltanha1 Deltakha1) and plasma membrane Na+ pumps (Deltaena1-4). Curiously, CHX20 did not enhance tolerance of mutants to moderate Na+ or high K+ stress. Instead, it restored growth of the mutant on medium with low K+ at slightly alkaline pH, but had no effect on growth at acidic pH. Green fluorescent protein-tagged CHX20 expressed in mesophyll protoplasts was localized mainly to membranes of the endosomal system. Furthermore, light-induced stomatal opening of the Arabidopsis mutants was insensitive to external pH and was impaired at high KCl. The results are consistent with the idea that, in exchanging K+ for H+, CHX20 maintains K+ homeostasis and influences pH under certain conditions. Together, these results provide genetic and biochemical evidence that one CHX protein plays a critical role in osmoregulation through K+ fluxes and possibly pH modulation of an active endomembrane system in guard cells. PMID- 17337535 TI - Role of cystathionine beta-lyase in catabolism of amino acids to sulfur volatiles by genetic variants of Lactobacillus helveticus CNRZ 32. AB - Catabolism of sulfur-containing amino acids plays an important role in the development of cheese flavor. During ripening, cystathionine beta-lyase (CBL) is believed to contribute to the formation of volatile sulfur compounds (VSCs) such as methanethiol and dimethyl disulfide. However, the role of CBL in the generation of VSCs from the catabolism of specific sulfur-containing amino acids is not well characterized. The objective of this study was to investigate the role of CBL in VSC formation by Lactobacillus helveticus CNRZ 32 using genetic variants of L. helveticus CNRZ 32 including the CBL-null mutant, complementation of the CBL-null mutant, and the CBL overexpression mutant. The formation of VSCs from methionine, cystathionine, and cysteine was determined in a model system using gas chromatography-mass spectrometry with solid-phase microextraction. With methionine as a substrate, CBL overexpression resulted in higher VSC production than that of wild-type L. helveticus CNRZ 32 or the CBL-null mutant. However, there were no differences in VSC production between the wild type and the CBL null mutant. With cystathionine, methanethiol production was detected from the CBL overexpression variant and complementation of the CBL-null mutant, implying that CBL may be involved in the conversion of cystathionine to methanethiol. With cysteine, no differences in VSC formation were observed between the wild type and genetic variants, indicating that CBL does not contribute to the conversion of cysteine. PMID- 17337536 TI - Diversity of lactic acid bacteria associated with fish and the fish farm environment, established by amplified rRNA gene restriction analysis. AB - Lactic acid bacteria have become a major source of concern for aquaculture in recent decades. In addition to true pathogenic species of worldwide significance, such as Streptococcus iniae and Lactococcus garvieae, several species have been reported to produce occasional fish mortalities in limited geographic areas, and many unidentifiable or ill-defined isolates are regularly isolated from fish or fish products. To clarify the nature and prevalence of different fish-associated bacteria belonging to the lactic acid bacterium group, a collection of 57 isolates of different origins was studied and compared with a set of 22 type strains, using amplified rRNA gene restriction analysis (ARDRA). Twelve distinct clusters were delineated on the basis of ARDRA profiles and were confirmed by sequencing of sodA and 16S rRNA genes. These clusters included the following: Lactococcus raffinolactis, L. garvieae, Lactococcus l., S. iniae, S. dysgalactiae, S. parauberis, S. agalactiae, Carnobacterium spp., the Enterococcus "faecium" group, a heterogeneous Enterococcus-like cluster comprising indiscernible representatives of Vagococcus fluvialis or the recently recognized V. carniphilus, V. salmoninarum, and Aerococcus spp. Interestingly, the L. lactis and L. raffinolactis clusters appeared to include many commensals of fish, so opportunistic infections caused by these species cannot be disregarded. The significance for fish populations and fish food processing of three or four genetic clusters of uncertain or complex definition, namely, Aerococcus and Enterococcus clusters, should be established more accurately. PMID- 17337537 TI - Considerations when using discriminant function analysis of antimicrobial resistance profiles to identify sources of fecal contamination of surface water in Michigan. AB - The goals of this study were to (i) identify issues that affect the ability of discriminant function analysis (DA) of antimicrobial resistance profiles to differentiate sources of fecal contamination, (ii) test the accuracy of DA from a known-source library of fecal Escherichia coli isolates with isolates from environmental samples, and (iii) apply this DA to classify E. coli from surface water. A repeated cross-sectional study was used to collect fecal and environmental samples from Michigan livestock, wild geese, and surface water for bacterial isolation, identification, and antimicrobial susceptibility testing using disk diffusion for 12 agents chosen for their importance in treating E. coli infections or for their use as animal feed additives. Nonparametric DA was used to classify E. coli by source species individually and by groups according to antimicrobial exposure. A modified backwards model-building approach was applied to create the best decision rules for isolate differentiation with the smallest number of antimicrobial agents. Decision rules were generated from fecal isolates and applied to environmental isolates to determine the effectiveness of DA for identifying sources of contamination. Principal component analysis was applied to describe differences in resistance patterns between species groups. The average rate of correct classification by DA was improved by reducing the numbers of species classifications and antimicrobial agents. DA was able to correctly classify environmental isolates when fewer than four classifications were used. Water sample isolates were classified by livestock type. An evaluation of the performance of DA must take into consideration relative contributions of random chance and the true discriminatory power of the decision rules. PMID- 17337538 TI - Bacterial degradation of N,N-diethyl-m-toluamide (DEET): cloning and heterologous expression of DEET hydrolase. AB - Pseudomonas putida DTB grew aerobically with N,N-diethyl-m-toluamide (DEET) as a sole carbon source, initially breaking it down into 3-methylbenzoate and diethylamine. The former was further metabolized via 3-methylcatechol and meta ring cleavage. A gene from DTB, dthA, was heterologously expressed and shown to encode the ability to hydrolyze DEET into 3-methylbenzoate and diethylamine. PMID- 17337539 TI - Role of lipid composition and lipid peroxidation in the sensitivity of fungal plant pathogens to aluminum chloride and sodium metabisulfite. AB - Aluminum chloride and sodium metabisulfite have shown high efficacy at low doses in controlling postharvest pathogens on potato tubers. Direct effects of these two salts included the loss of cell membrane integrity in exposed pathogens. In this work, four fungal potato pathogens were studied in order to elucidate the role of membrane lipids and lipid peroxidation in the relative sensitivity of microorganisms exposed to these salts. Inhibition of mycelial growth in these fungi varied considerably and revealed sensitivity groups within the tested fungi. Analysis of fatty acids in these fungi demonstrated that sensitivity was related to high intrinsic fatty acid unsaturation. When exposed to the antifungal salts, sensitive fungi demonstrated a loss of fatty acid unsaturation, which was accompanied by an elevation in malondialdehyde content (a biochemical marker of lipid peroxidation). Our data suggest that aluminum chloride and sodium metabisulfite could induce lipid peroxidation in sensitive fungi, which may promote the ensuing loss of integrity in the plasma membrane. This direct effect on fungal membranes may contribute, at least in part, to the observed antimicrobial effects of these two salts. PMID- 17337540 TI - Competition for light between toxic and nontoxic strains of the harmful cyanobacterium Microcystis. AB - The cyanobacterium Microcystis can produce microcystins, a family of toxins that are of major concern in water management. In several lakes, the average microcystin content per cell gradually declines from high levels at the onset of Microcystis blooms to low levels at the height of the bloom. Such seasonal dynamics might result from a succession of toxic to nontoxic strains. To investigate this hypothesis, we ran competition experiments with two toxic and two nontoxic Microcystis strains using light-limited chemostats. The population dynamics of these closely related strains were monitored by means of characteristic changes in light absorbance spectra and by PCR amplification of the rRNA internal transcribed spacer region in combination with denaturing gradient gel electrophoresis, which allowed identification and semiquantification of the competing strains. In all experiments, the toxic strains lost competition for light from nontoxic strains. As a consequence, the total microcystin concentrations in the competition experiments gradually declined. We did not find evidence for allelopathic interactions, as nontoxic strains became dominant even when toxic strains were given a major initial advantage. These findings show that, in our experiments, nontoxic strains of Microcystis were better competitors for light than toxic strains. The generality of this finding deserves further investigation with other Microcystis strains. The competitive replacement of toxic by nontoxic strains offers a plausible explanation for the gradual decrease in average toxicity per cell during the development of dense Microcystis blooms. PMID- 17337541 TI - Survival of Mycobacterium avium, Legionella pneumophila, Escherichia coli, and caliciviruses in drinking water-associated biofilms grown under high-shear turbulent flow. AB - Most of the bacteria in drinking water distribution systems are associated with biofilms. In biofilms, their nutrient supply is better than in water, and biofilms can provide shelter against disinfection. We used a Propella biofilm reactor for studying the survival of Mycobacterium avium, Legionella pneumophila, Escherichia coli, and canine calicivirus (CaCV) (as a surrogate for human norovirus) in drinking water biofilms grown under high-shear turbulent-flow conditions. The numbers of M. avium and L. pneumophila were analyzed with both culture methods and with peptide nucleic acid fluorescence in situ hybridization (FISH) methods. Even though the numbers of pathogens in biofilms decreased during the experiments, M. avium and L. pneumophila survived in biofilms for more than 2 to 4 weeks in culturable forms. CaCV was detectable with a reverse transcription PCR method in biofilms for more than 3 weeks. E. coli was detectable by culture for only 4 days in biofilms and 8 days in water, suggesting that it is a poor indicator of the presence of certain waterborne pathogens. With L. pneumophila and M. avium, culture methods underestimated the numbers of bacteria present compared to the FISH results. This study clearly proved that pathogenic bacteria entering water distribution systems can survive in biofilms for at least several weeks, even under conditions of high-shear turbulent flow, and may be a risk to water consumers. Also, considering the low number of virus particles needed to result in an infection, their extended survival in biofilms must be taken into account as a risk for the consumer. PMID- 17337542 TI - Cometabolic degradation of dibenzofuran and dibenzothiophene by a newly isolated carbazole-degrading Sphingomonas sp. strain. AB - A carbazole-utilizing bacterium was isolated by enrichment from petroleum contaminated soil. The isolate, designated Sphingomonas sp. strain XLDN2-5, could utilize carbazole (CA) as the sole source of carbon, nitrogen, and energy. Washed cells of strain XLDN2-5 were shown to be capable of degrading dibenzofuran (DBF) and dibenzothiophene (DBT). Examination of metabolites suggested that XLDN2-5 degraded DBF to 2-hydroxy-6-(2-hydroxyphenyl)-6-oxo-2,4-hexadienic acid and subsequently to salicylic acid through the angular dioxygenation pathway. In contrast to DBF, strain XLDN2-5 could transform DBT through the ring cleavage and sulfoxidation pathways. Sphingomonas sp. strain XLDN2-5 could cometabolically degrade DBF and DBT in the growing system using CA as a substrate. After 40 h of incubation, 90% of DBT was transformed, and CA and DBF were completely removed. These results suggested that strain XLDN2-5 might be useful in the bioremediation of environments contaminated by these compounds. PMID- 17337543 TI - Lack of control of nitrite assimilation by ammonium in an oceanic picocyanobacterium, Synechococcus sp. strain WH 8103. AB - In cyanobacteria, the transcriptional activator NtcA is involved in global nitrogen control and, in the absence of ammonium, regulates the expression of genes involved in the assimilation of alternative nitrogen sources. The oceanic picocyanobacterium Synechococcus sp. strain WH 8103 harbors a copy of ntcA, but in the present study, we show that unlike other marine cyanobacteria that have been investigated, this strain is capable of coassimilating nitrite when grown in the presence of ammonium. Transcript levels for the genes encoding the nitrate/nitrite-bispecific permease NrtP and nitrate reductase (NarB) were substantially down-regulated by ammonium, whereas the abundances of nitrite reductase (NirA) transcripts were similar in nitrite- and ammonium-grown cells. The growth of Synechococcus sp. strain WH 8103 in medium containing both ammonium and nitrite resulted in only minor changes in the expression profile in comparison to that of nitrite-grown cells with the exception that the gene encoding the high-affinity ammonium transporter Amt1 was down-regulated to the levels seen in ammonium-grown cells. Whereas the expression of nrtP, narB, and amt1 appears to be NtcA dependent in this marine cyanobacterium, the transcription and expression of nirA appear not to be. The ability to coassimilate nitrite and reduced-nitrogen sources like ammonium may be an adaptive trait that enables oceanic strains like Synechococcus sp. strain WH 8103 to exploit the low nitrite concentrations found in oceanic surface waters that are not available to their principal and more numerous competitor, Prochlorococcus. PMID- 17337544 TI - Acidobacteria phylum sequences in uranium-contaminated subsurface sediments greatly expand the known diversity within the phylum. AB - The abundance and composition of bacteria of the phylum Acidobacteria were surveyed in subsurface sediments from uranium-contaminated sites using amplification of 16S rRNA genes followed by clone/sequence analysis. Analysis of sequences from this study and public databases produced a revised and greatly expanded phylogeny of the Acidobacteria phylum consisting of 26 subgroups. PMID- 17337545 TI - Dynamics of genomic-library enrichment and identification of solvent tolerance genes for Clostridium acetobutylicum. AB - A Clostridium acetobutylicum ATCC 824 genomic library was constructed using randomly sheared DNA. Library inserts conferring increased tolerance to 1-butanol were isolated using two protocols. Protocol I utilized a single round of butanol challenges in batch culture, while protocol II, which gave clearly superior outcomes, was based on the serial transfer of stationary-phase cultures into progressively higher butanol concentrations. DNA microarray analysis made a high resolution assessment of the dynamic process of library enrichment possible for the first time. Protocol I yielded a library insert containing the entire coding region of the gene CAC0003 (which codes for a protein of unknown function) but also several DNA fragments containing promoter regions. Protocol II enabled the successful identification of DNA fragments containing several intact genes conferring preferential growth under conditions of butanol stress. Since expression using the employed library is possible only from natural promoters, among the enriched genes, we identified 16 genes that constitute the first cistron of a transcriptional unit. These genes include four transcriptional regulators (CAC0977, CAC1463, CAC1869, and CAC2495). After subcloning plasmids carrying the CAC0003 and CAC1869 genes, strains 824(pCAC0003) and 824(pCAC1869) exhibited 13% and an 81% increases, respectively, in butanol tolerance relative to the plasmid control strain. 824(pCAC1869) consistently grew to higher cell densities in challenged and unchallenged cultures and exhibited prolonged metabolism. Our serial enrichment approach provided a more detailed understanding of the dynamic process of library enrichment under conditions of selective growth. Further characterization of the genes identified in this study will likely enhance our understanding of the complex phenotype of solvent tolerance. PMID- 17337546 TI - Analysis of the two-peptide bacteriocins lactococcin G and enterocin 1071 by site directed mutagenesis. AB - The two peptides (Lcn-alpha and Lcn-beta) of the two-peptide bacteriocin lactococcin G (Lcn) were changed by stepwise site-directed mutagenesis into the corresponding peptides (Ent-alpha and Ent-beta) of the two-peptide bacteriocin enterocin 1071 (Ent), and the potencies and specificities of the various hybrid constructs were determined. Both Lcn and, to a lesser extent, Ent were active against all the tested lactococcal strains, but only Ent was active against the tested enterococcal strains. The two bacteriocins thus differed in their relative potencies to various target cells, despite their sequence similarities. The hybrid combination Lcn-alpha+Ent-beta had low potency against all strains tested, indicating that these two peptides do not interact optimally. The reciprocal hybrid combination (i.e., Ent-alpha+Lcn-beta), in contrast, was highly potent, indicating that these two peptides may form a functional antimicrobial unit. In fact, this hybrid combination (Ent-alpha+Lcn-beta) was more potent against lactococcal strains than wild-type Ent was (i.e., Ent-alpha+Ent-beta), but it was inactive against enterococcal strains (in contrast to Ent but similar to Lcn). The observation that Ent-alpha is more active against lactococci in combination with Lcn-beta and more active against enterococci in combination with Ent-beta suggests that the beta peptide is an important determinant of target cell specificity. Especially the N-terminal residues of the beta peptide seem to be important for specificity, since Ent-alpha combined with an Ent-beta variant with Ent-to-Lcn mutations at positions 1 to 4, 7, 9, and 10 was >150-fold less active against enterococcal strains but one to four times more active against lactococcal strains than Ent-alpha+Ent-beta. Moreover, Ent-to-Lcn single-residue mutations in the region spanning residues 1 to 7 in Ent-beta had a more detrimental effect on the activity against enterococci than on that against lactococcal strains. Of the single-residue mutations made in the N-terminal region of the alpha peptide, the Ent-to-Lcn mutations N8Q and P12R in Ent-alpha influenced specificity, as follows: the N8Q mutation had no effect on activity against tested enterococcal strains but increased the activity 2- to 4-fold against the tested lactococcal strains, and the P12R mutation reduced the activity >150-fold and only approximately 2-fold against enterococcal and lactococcal strains, respectively. Changing residues in the C-terminal half/part of the Lcn peptides (residues 20 to 39 and 25 to 35 in Lcn-alpha and Lcn-beta, respectively) to those found in the corresponding Ent peptides did not have a marked effect on the activity, but there was an approximately 10-fold or greater reduction in the activity upon also introducing Lcn-to-Ent mutations in the mid region (residues 8 to 19 and 9 to 24 in Lcn-alpha and Lcn-beta, respectively). Interestingly, the Lcn-to-Ent F19L+G20A mutation in an Lcn-Ent-beta hybrid peptide was more detrimental when the altered peptide was combined with Lcn-alpha (>10-fold reduction) than when it was combined with Ent-alpha ( approximately 2 fold reduction), suggesting that residues 19 and 20 (which are part of a GXXXG motif) in the beta peptide may be involved in a specific interaction with the cognate alpha peptide. It is also noteworthy that the K2P and A7P mutations in Lcn-beta reduced the activity only approximately 2-fold, suggesting that the first seven residues in the beta peptides do not form an alpha-helix. PMID- 17337547 TI - Biogeography of actinomycete communities and type II polyketide synthase genes in soils collected in New Jersey and Central Asia. AB - Soil microbial communities are believed to be comprised of thousands of different bacterial species. One prevailing idea is that "everything is everywhere, and the environment selects," implying that all types of bacteria are present in all environments where their growth requirements are met. We tested this hypothesis using actinomycete communities and type II polyketide synthase (PKS) genes found in soils collected from New Jersey and Uzbekistan (n = 91). Terminal restriction fragment length polymorphism analysis using actinomycete 16S rRNA and type II PKS genes was employed to determine community profiles. The terminal fragment frequencies in soil samples had a lognormal distribution, indicating that the majority of actinomycete phylotypes and PKS pathways are present infrequently in the environment. Less than 1% of peaks were detected in more than 50% of samples, and as many as 18% of the fragments were unique and detected in only one sample. Actinomycete 16S rRNA fingerprints clustered by country of origin, indicating that unique populations are present in North America and Central Asia. Sequence analysis of type II PKS gene fragments cloned from Uzbek soil revealed 35 novel sequence clades whose levels of identity to genes in the GenBank database ranged from 68 to 92%. The data indicate that actinomycetes are patchily distributed but that distinct populations are present in North American and Central Asia. These results have implications for microbial bioprospecting and indicate that the cosmopolitan actinomycete species and PKS pathways may account for only a small proportion of the total diversity in soil. PMID- 17337548 TI - Multiple environmental stress tests show no common phenotypes shared among contemporary epidemic strains of Salmonella enterica. AB - Phenotypic traits of coexisting epidemic and nonepidemic strains of Salmonella enterica serovars Typhimurium and Newport were compared. Different stress conditions were relatively more or less favorable for the epidemic strains. Transcriptional analysis identified specific upregulated genes during defined stress conditions, but there were no common traits shared by epidemic serovars. PMID- 17337549 TI - New method for evaluation of genotoxicity, based on the use of real-time PCR and lysogenic gram-positive and gram-negative bacteria. AB - A method for the detection of the SOS response as measured by the liberation of resident prophages from the genomes of their hosts is described. It is based on the use of two converging oligonucleotides that flank the attP attachment site of the phage as primers for real-time PCR. Amplification was observed only after the phage DNA became excised. The system responds to both chemicals and physical conditions. Quantitative data on the concentration and/or potency of the genotoxic condition were obtained. Results can be achieved within 1 day and are less susceptible to possible toxic effects than phage generation or other methods that require DNA synthesis. The use of both gram-positive and gram-negative bacteria widens the range of compounds that can be tested because it eliminates impermeability problems derived from the particular composition of each cell wall type. PMID- 17337550 TI - The alternative sigma factor sigma B and the virulence gene regulator PrfA both regulate transcription of Listeria monocytogenes internalins. AB - Some Listeria monocytogenes internalins are recognized as contributing to invasion of mammalian tissue culture cells. While PrfA is well established as a positive regulator of L. monocytogenes virulence gene expression, the stress responsive sigma(B) has been recognized only recently as contributing to expression of virulence genes, including some that encode internalins. To measure the relative contributions of PrfA and sigma(B) to internalin gene transcription, we used reverse transcription-PCR to quantify transcript levels for eight internalin genes (inlA, inlB, inlC, inlC2, inlD, inlE, inlF, and inlG) in L. monocytogenes 10403S and in isogenic Delta prfA, Delta sigB, and Delta sigB Delta prfA strains. Strains were grown under defined conditions to produce (i) active PrfA, (ii) active sigma(B) and active PrfA, (iii) inactive PrfA, and (iv) active sigma(B) and inactive PrfA. Under the conditions tested, sigma(B) and PrfA contributed differentially to the expression of the various internalins such that (i) both sigma(B) and PrfA contributed to inlA and inlB transcription, (ii) only PrfA contributed to inlC transcription, (iii) only sigma(B) contributed to inlC2 and inlD transcription, and (iv) neither sigma(B) nor PrfA contributed to inlF and inlG transcription. inlE transcript levels were undetectable. The important role for sigma(B) in regulating expression of L. monocytogenes internalins suggests that exposure of this organism to environmental stress conditions, such as those encountered in the gastrointestinal tract, may activate internalin transcription. Interplay between sigma(B) and PrfA also appears to be critical for regulating transcription of some virulence genes, including inlA, inlB, and prfA. PMID- 17337551 TI - First evidence of division and accumulation of viable but nonculturable Pseudomonas fluorescens cells on surfaces subjected to conditions encountered at meat processing premises. AB - Cleaning and disinfection of open surfaces in food industry premises leave some microorganisms behind; these microorganisms build up a resident flora on the surfaces. Our goal was to explore the phenomena involved in the establishment of this biofilm. Ceramic coupons were contaminated, once only, with Pseudomonas fluorescens suspended in meat exudate incubated at 10 degrees C. The mean adhering population after 1 day was 10(2) CFU x cm(-2) and 10(3) total cells x cm(-2), i.e., the total number of cells stained by DAPI (4',6'-diamidino-2 phenylindole). The coupons were subjected daily to a cleaning product, a disinfectant, and a further soiling with exudate. The result was a striking difference between the numbers of CFU, which reached 10(4) CFU x cm(-2), and the numbers of total cells, which reached 2 x 10(6) cells x cm(-2) in 10 days. By using hypotheses all leading to an overestimation of the number of dead cells, we showed that the quantity of nonculturable cells (DAPI-positive cells minus CFU) observed cannot be accounted for as an accumulation of dead cells. Some nonculturable cells are therefore dividing on the surface, although cell division is unable to continue to the stage of macrocolony formation on agar. The same phenomenon was observed when only a chlorinated alkaline product was used and the number of cells capable of reducing 5-cyano-2,3-ditolyl tetrazolium chloride was close to the number of total cells, confirming that most nonculturable cells are viable but nonculturable. Furthermore, the daily shock applied to the cells does not prompt them to enter a new lag phase. Since a single application of microorganisms is sufficient to produce this accumulation of cells, it appears that the phenomenon is inevitable on open surfaces in food industry premises. PMID- 17337552 TI - Two host-induced Ralstonia solanacearum genes, acrA and dinF, encode multidrug efflux pumps and contribute to bacterial wilt virulence. AB - Multidrug efflux pumps (MDRs) are hypothesized to protect pathogenic bacteria from toxic host defense compounds. We created mutations in the Ralstonia solanacearum acrA and dinF genes, which encode putative MDRs in the broad-host range plant pathogen. Both mutations reduced the ability of R. solanacearum to grow in the presence of various toxic compounds, including antibiotics, phytoalexins, and detergents. Both acrAB and dinF mutants were significantly less virulent on the tomato plant than the wild-type strain. Complementation restored near-wild-type levels of virulence to both mutants. Addition of either dinF or acrAB to Escherichia coli MDR mutants KAM3 and KAM32 restored the resistance of these strains to several toxins, demonstrating that the R. solanacearum genes can function heterologously to complement known MDR mutations. Toxic and DNA-damaging compounds induced expression of acrA and dinF, as did growth in both susceptible and resistant tomato plants. Carbon limitation also increased expression of acrA and dinF, while the stress-related sigma factor RpoS was required at a high cell density (>10(7) CFU/ml) to obtain wild-type levels of acrA expression both in minimal medium and in planta. The type III secretion system regulator HrpB negatively regulated dinF expression in culture at high cell densities. Together, these results show that acrAB and dinF encode MDRs in R. solanacearum and that they contribute to the overall aggressiveness of this phytopathogen, probably by protecting the bacterium from the toxic effects of host antimicrobial compounds. PMID- 17337553 TI - Influence of vitamin B12 and cocultures on the growth of Dehalococcoides isolates in defined medium. AB - Bacteria belonging to the genus Dehalococcoides play a key role in the complete detoxification of chloroethenes as these organisms are the only microbes known to be capable of dechlorination beyond dichloroethenes to vinyl chloride (VC) and ethene. However, Dehalococcoides strains usually grow slowly with a doubling time of 1 to 2 days and have complex nutritional requirements. Here we describe the growth of Dehalococcoides ethenogenes 195 in a defined mineral salts medium, improved growth of strain 195 when the medium was amended with high concentrations of vitamin B(12), and a strategy for maintaining Dehalococcoides strains on lactate by growing them in consortia. Although strain 195 could grow in defined medium spiked with approximately 0.5 mM trichloroethene (TCE) and 0.001 mg/liter vitamin B(12), the TCE dechlorination and cellular growth rates doubled when the vitamin B(12) concentration was increased 25-fold to 0.025 mg/liter. In addition, the final ratios of ethene to VC increased when the higher vitamin concentration was used, which reflected the key role that cobalamin plays in dechlorination reactions. No further improvement in dechlorination or growth was observed when the vitamin B(12) concentration was increased to more than 0.025 mg/liter. In defined consortia containing strain 195 along with Desulfovibrio desulfuricans and/or Acetobacterium woodii and containing lactate as the electron donor, tetrachloroethene ( approximately 0.4 mM) was completely dechlorinated to VC and ethene and there was concomitant growth of Dehalococcoides cells. In the cultures that also contained D. desulfuricans and/or A. woodii, strain 195 cells grew to densities that were 1.5 times greater than the densities obtained when the isolate was grown alone. The ratio of ethene to VC was highest in the presence of A. woodii, an organism that generates cobalamin de novo during metabolism. These findings demonstrate that the growth of D. ethenogenes strain 195 in defined medium can be optimized by providing high concentrations of vitamin B(12) and that this strain can be grown to higher densities in cocultures with fermenters that convert lactate to generate the required hydrogen and acetate and that may enhance the availability of vitamin B(12). PMID- 17337555 TI - Actively growing bacteria in the inland sea of Japan, identified by combined bromodeoxyuridine immunocapture and denaturing gradient gel electrophoresis. AB - A fundamental question in microbial oceanography concerns the relationship between prokaryote diversity and biogeochemical function in an ecosystem context. We combined bromodeoxyuridine (BrdU) magnetic bead immunocapture and PCR denaturing gradient gel electrophoresis (BUMP-DGGE) to examine phylotype-specific growth in natural marine assemblages. We also examined a broad range of marine bacterial isolates to determine their abilities to incorporate BrdU in order to test the validity of the method for application to diverse marine assemblages. We found that 27 of 29 isolates belonging to different taxa could incorporate BrdU. BUMP-DGGE analysis revealed phylogenetic affiliations of DNA-synthesizing, presumably actively growing bacteria across a eutrophic to mesotrophic transect in the Inland Sea of Japan. We found that the BrdU-incorporating (growing) communities were substantially different from the total communities. The majority (34/56) of phylotypes incorporated BrdU and were presumably growing, and these phylotypes comprised 10 alphaproteobacteria, 1 betaproteobacterium, 11 gammaproteobacteria, 11 Cytophaga-Flavobacterium-Bacteroides group bacteria, and 1 unclassified bacterium. All BrdU-responsive alphaproteobacteria were members of the Rhodobacterales, suggesting that such bacteria were dominant in the growing alphaproteobacterial populations in our samples. The BrdU-responsive gammaproteobacteria belonged to the Oceanospirillales, the SAR86 cluster, the Pseudomonadales, the Alteromonadales, and the Vibrionales. Thus, contemporaneous cooccurrence of diverse actively growing bacterial taxa was a consistent pattern in our biogeochemically varied study area. PMID- 17337556 TI - Transcriptional response of Saccharomyces cerevisiae to different nitrogen concentrations during alcoholic fermentation. AB - Gene expression profiles of a wine strain of Saccharomyces cerevisiae PYCC4072 were monitored during alcoholic fermentations with three different nitrogen supplies: (i) control fermentation (with enough nitrogen to complete sugar fermentation), (ii) nitrogen-limiting fermentation, and (iii) the addition of nitrogen to the nitrogen-limiting fermentation (refed fermentation). Approximately 70% of the yeast transcriptome was altered in at least one of the fermentation stages studied, revealing the continuous adjustment of yeast cells to stressful conditions. Nitrogen concentration had a decisive effect on gene expression during fermentation. The largest changes in transcription profiles were observed when the early time points of the N-limiting and control fermentations were compared. Despite the high levels of glucose present in the media, the early responses of yeast cells to low nitrogen were characterized by the induction of genes involved in oxidative glucose metabolism, including a significant number of mitochondrial associated genes resembling the yeast cell response to glucose starvation. As the N-limiting fermentation progressed, a general downregulation of genes associated with catabolism was observed. Surprisingly, genes encoding ribosomal proteins and involved in ribosome biogenesis showed a slight increase during N starvation; besides, genes that comprise the RiBi regulon behaved distinctively under the different experimental conditions. Here, for the first time, the global response of nitrogen-depleted cells to nitrogen addition under enological conditions is described. An important gene expression reprogramming occurred after nitrogen addition; this reprogramming affected genes involved in glycolysis, thiamine metabolism, and energy pathways, which enabled the yeast strain to overcome the previous nitrogen starvation stress and restart alcoholic fermentation. PMID- 17337554 TI - Alignment-independent comparisons of human gastrointestinal tract microbial communities in a multidimensional 16S rRNA gene evolutionary space. AB - We present a novel approach for comparing 16S rRNA gene clone libraries that is independent of both DNA sequence alignment and definition of bacterial phylogroups. These steps are the major bottlenecks in current microbial comparative analyses. We used direct comparisons of taxon density distributions in an absolute evolutionary coordinate space. The coordinate space was generated by using alignment-independent bilinear multivariate modeling. Statistical analyses for clone library comparisons were based on multivariate analysis of variance, partial least-squares regression, and permutations. Clone libraries from both adult and infant gastrointestinal tract microbial communities were used as biological models. We reanalyzed a library consisting of 11,831 clones covering complete colons from three healthy adults in addition to a smaller 390 clone library from infant feces. We show that it is possible to extract detailed information about microbial community structures using our alignment-independent method. Our density distribution analysis is also very efficient with respect to computer operation time, meeting the future requirements of large-scale screenings to understand the diversity and dynamics of microbial communities. PMID- 17337557 TI - Diversity and metabolism of marine bacteria cultivated on dissolved DNA. AB - Dissolved DNA (dDNA) is a potentially important source of energy and nutrients in aquatic ecosystems. However, little is known about the identity, metabolism, and interactions of the microorganisms capable of consuming dDNA. Bacteria from Eel Pond (Woods Hole, MA) were cultivated on low-molecular-weight (LMW) or high molecular-weight (HMW) dDNA, which served as the primary source of carbon, nitrogen, and phosphorus. Cloning and sequencing of 16S rRNA genes revealed that distinct bacterial assemblages with comparable levels of taxon richness developed on LMW and HMW dDNA. Since the LMW and HMW dDNA used in this study were stoichiometrically identical, the results confirm that the size alone of dissolved organic matter can influence bacterial community composition. Variation in the growth and metabolism of isolates provided insight into mechanisms that may have generated differences in bacterial community composition. For example, bacteria from LMW dDNA enrichments generally grew better on LMW dDNA than on HMW dDNA. In contrast, bacteria isolated from HMW dDNA enrichments were more effective at degrading HMW dDNA than bacteria isolated from LMW dDNA enrichments. Thus, marine bacteria may experience a trade-off between their ability to compete for LMW dDNA and their ability to access HMW dDNA via extracellular nuclease production. Together, the results of this study suggest that dDNA turnover in marine ecosystems may involve a succession of microbial assemblages with specialized ecological strategies. PMID- 17337558 TI - Refined medium for direct isolation of Vibrio vulnificus from oyster tissue and seawater. AB - We have developed a new medium for the direct isolation of Vibrio vulnificus from water and oyster samples. The medium was shown in laboratory and field studies to be highly selective without providing preferential isolation of either V. vulnificus genotype. PMID- 17337559 TI - Thiols in nitric oxide synthase-containing Nocardia sp. strain NRRL 5646. AB - Mycothiol (MSH) [1-D-myo-inosityl-2-(N-acetyl-l-cysteinyl)amido-2-deoxy-alpha-D glucopyranoside], isolated as the bimane derivative, was established to be the major thiol in Nocardia sp. strain NRRL 5646, a species most closely related to Nocardia brasiliensis strain DSM 43758(T). Thiol formation and detection of MSH dependent formaldehyde dehydrogenase activity in cell extracts are relevant to the possible modulation of nitric oxide toxicity generated by strain NRRL 5646. PMID- 17337560 TI - Development of a genetic system for the chemolithoautotrophic bacterium Thiobacillus denitrificans. AB - Thiobacillus denitrificans is a widespread, chemolithoautotrophic bacterium with an unusual and environmentally relevant metabolic repertoire, which includes its ability to couple denitrification to sulfur compound oxidation; to catalyze anaerobic, nitrate-dependent oxidation of Fe(II) and U(IV); and to oxidize mineral electron donors. Recent analysis of its genome sequence also revealed the presence of genes encoding two [NiFe]hydrogenases, whose role in metabolism is unclear, as the sequenced strain does not appear to be able to grow on hydrogen as a sole electron donor under denitrifying conditions. In this study, we report the development of a genetic system for T. denitrificans, with which insertion mutations can be introduced by homologous recombination and complemented in trans. The antibiotic sensitivity of T. denitrificans was characterized, and a procedure for transformation with foreign DNA by electroporation was established. Insertion mutations were generated by in vitro transposition, the mutated genes were amplified by the PCR, and the amplicons were introduced into T. denitrificans by electroporation. The IncP plasmid pRR10 was found to be a useful vector for complementation. The effectiveness of the genetic system was demonstrated with the hynL gene, which encodes the large subunit of a [NiFe]hydrogenase. Interruption of hynL in a hynL::kan mutant resulted in a 75% decrease in specific hydrogenase activity relative to the wild type, whereas complementation of the hynL mutation resulted in activity that was 50% greater than that of the wild type. The availability of a genetic system in T. denitrificans will facilitate our understanding of the genetics and biochemistry underlying its unusual metabolism. PMID- 17337561 TI - Temperature-dependent expression of Listeria monocytogenes internalin and internalin-like genes suggests functional diversity of these proteins among the listeriae. AB - The Listeria monocytogenes genome contains genes encoding several internalins and internalin-like proteins. As L. monocytogenes is present in many environments and can infect numerous, diverse host species, the environmental temperature was hypothesized to be a signal that might affect internalin gene transcription. A subgenomic microarray was used to investigate temperature-dependent transcription of 24 members of the internalin gene family in L. monocytogenes 10403S. The levels of internalin gene transcripts for cells grown at 37 degrees C were compared to the levels of transcripts for cells grown at 16, 30, and 42 degrees C using competitive microarray hybridization, and the results were confirmed by performing quantitative reverse transcriptase PCR for 14 internalin genes. Based on these studies, the internalin genes can be grouped into the following five temperature-dependent categories: (i) four sigma(B)-dependent internalin genes (inlC2, inlD, lmo0331, and lmo0610) with the highest levels of transcripts at 16 degrees C and generally the lowest levels of transcripts at 37 degrees C; (ii) three partially PrfA-dependent internalin genes (inlA, inlB, and inlC) with the lowest levels of transcripts at 16 degrees C and the highest levels of transcripts at 37 and 42 degrees C; (iii) four genes (inlG, inlJ, lmo0514, and lmo1290) with the lowest levels of transcripts at 16 degrees C and the highest levels of transcripts at 30 and/or 37 degrees C; (iv) one gene (lmo0327) with the highest levels of transcripts at 16 degrees C and low levels of transcripts at higher temperatures; and (v) 12 internalin genes with no differences in the levels of transcripts at the temperatures used in this study. The temperature dependent transcription patterns suggest that the relative importance of different internalins varies by environment, which may provide insight into the specific functions of these proteins. PMID- 17337562 TI - Characterization of nontoxic and toxin-producing strains of Alexandrium minutum (Dinophyceae) in Irish coastal waters. AB - A comparative analysis of the morphology, toxin composition, and ribosomal DNA (rDNA) sequences was performed on a suite of clonal cultures of the potentially toxic dinoflagellate Alexandrium minutum Halim. These were established from resting cysts or vegetative cells isolated from sediment and water samples taken from the south and west coasts of Ireland. Results revealed that strains were indistinguishable, both morphologically and through the sequencing of the D1-D2 domain of the large subunit and the ITS1-5.8S-ITS2 regions of the rDNA. High performance liquid chromatography fluorescence detection analysis, however, showed that only strains derived from retentive inlets on the southern Irish coast synthesized paralytic shellfish poisoning (PSP) toxins (GTX2 and GTX3), whereas all strains of A. minutum isolated from the west coast were nontoxic. Toxin analysis of net hauls, taken when A. minutum vegetative cells were in the water column, revealed no PSP toxins in samples from Killary Harbor (western coast), whereas GTX2 and GTX3 were detected in samples from Cork Harbor (southern coast). These results confirm the identity of A. minutum as the most probable causative organism for historical occurrences of contamination of shellfish with PSP toxins in Cork Harbor. Finally, random amplification of polymorphic DNA was carried out to determine the degree of polymorphism among strains. The analysis showed that all toxic strains from Cork Harbor clustered together and that a separate cluster grouped all nontoxic strains from the western coast. PMID- 17337563 TI - Biofilm cohesiveness measurement using a novel atomic force microscopy methodology. AB - Biofilms can be undesirable, as in those covering medical implants, and beneficial, such as when they are used for waste treatment. Because cohesive strength is a primary factor affecting the balance between growth and detachment, its quantification is essential in understanding, predicting, and modeling biofilm development. In this study, we developed a novel atomic force microscopy (AFM) method for reproducibly measuring, in situ, the cohesive energy levels of moist 1-day biofilms. The biofilm was grown from an undefined mixed culture taken from activated sludge. The volume of biofilm displaced and the corresponding frictional energy dissipated were determined as a function of biofilm depth, resulting in the calculation of the cohesive energy. Our results showed that cohesive energy increased with biofilm depth, from 0.10 +/- 0.07 nJ/microm(3) to 2.05 +/- 0.62 nJ/microm(3). This observation was reproducible, with four different biofilms showing the same behavior. Cohesive energy also increased from 0.10 +/- 0.07 nJ/microm(3) to 1.98 +/- 0.34 nJ/microm(3) when calcium (10 mM) was added to the reactor during biofilm cultivation. These results agree with previous reports on calcium increasing the cohesiveness of biofilms. This AFM based technique can be performed with available off-the-shelf instrumentation. It could therefore be widely used to examine biofilm cohesion under a variety of conditions. PMID- 17337564 TI - Cloning, characterization, and molecular application of a beta-agarase gene from Vibrio sp. strain V134. AB - V134, a marine isolate of the Vibrio genus, was found to produce a new beta agarase of the GH16 family. The relevant agarase gene agaV was cloned from V134 and conditionally expressed in Escherichia coli. Enzyme activity analysis revealed that the optimum temperature and pH for the purified recombinant agarase were around 40 degrees C and 7.0. AgaV was demonstrated to be useful in two aspects: first, as an agarolytic enzyme, the purified recombinant AgaV could be employed in the recovery of DNA from agarose gels; second, as a secretion protein, AgaV was explored at the genetic level and used as a reporter in the construction of a secretion signal trap which proved to be a simple and efficient molecular tool for the selection of genes encoding secretion proteins from both gram-positive and gram-negative bacteria. PMID- 17337565 TI - Effect of protein, polysaccharide, and oxygen concentration profiles on biofilm cohesiveness. AB - It is important to control biofilm cohesiveness to optimize process performance. In this study, a membrane-aerated biofilm reactor inoculated with activated sludge was used to grow mixed-culture biofilms of different ages and thicknesses. The cohesions, or cohesive energy levels per unit volume of biofilm, based on a reproducible method using atomic force microscopy (F. Ahimou, M. J. Semmens, P. J. Novak, and G. Haugstad, Appl. Environ. Microbiol. 73:2897-2904, 2007), were determined at different locations within the depths of the biofilms. In addition, the protein and polysaccharide concentrations within the biofilm depths, as well as the dissolved oxygen (DO) concentration profiles within the biofilms, were measured. It was found that biofilm cohesion increased with depth but not with age. Level of biofilm cohesive energy per unit volume was strongly correlated with biofilm polysaccharide concentration, which increased with depth in the membrane-aerated biofilm. In a 12-day-old biofilm, DO also increased with depth and may therefore be linked to polysaccharide production. In contrast, protein concentration was relatively constant within the biofilm and did not appear to influence cohesion. PMID- 17337566 TI - Characterization of extended-host-range pseudo-T-even bacteriophage Kpp95 isolated on Klebsiella pneumoniae. AB - Kpp95, isolated on Klebsiella pneumoniae, is a bacteriophage with the morphology of T4-type phages and is capable of rapid lysis of host cells. Its double stranded genomic DNA (ca. 175 kb, estimated by pulsed-field gel electrophoresis) can be cut only by restriction endonucleases with a cleavage site flanked either by A and T or by T, as tested, suggesting that it contains the modified derivative(s) of G and/or C. Over 26 protein bands were visualized upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the virion proteins. N terminal sequencing indicated that the most abundant band (46 kDa) is the major coat protein (gp23) which has been cleaved from a signal peptide likely with a length similar to that of T4. Phylogenetic analyses based on the sequences of the central region (263 amino acid residues) of gp23 and the full length of gp18 and gp19 placed Kpp95 among the pseudo-T-even subgroup, most closely related to the coliphage JS98. In addition to being able to lyse many extended-spectrum beta lactamase strains of K. pneumoniae, Kpp95 can lyse Klebsiella oxytoca, Enterobacter agglomerans, and Serratia marcescens cells. Thus, Kpp95 deserves further studies for development as a component of a therapeutic cocktail, owing to its high efficiencies of host lysis plus extended host range. PMID- 17337567 TI - Ex vivo stability of the rodent-borne Hantaan virus in comparison to that of arthropod-borne members of the Bunyaviridae family. AB - The possible effect of virus adaptation to different transmission routes on virus stability in the environment is not well known. In this study we have compared the stabilities of three viruses within the Bunyaviridae family: the rodent-borne Hantavirus Hantaan virus (HTNV), the sand fly-borne Phlebovirus sandfly fever Sicilian virus (SFSV), and the tick-borne Nairovirus Crimean-Congo hemorrhagic fever virus (CCHFV). These viruses differ in their transmission routes: SFSV and CCHFV are vector borne, whereas HTNV is spread directly between its hosts, and to humans, via the environment. We studied whether these viruses differed regarding stability when kept outside of the host. Viral survival was analyzed at different time points upon exposure to different temperatures (4 degrees C, 20 degrees C, and 37 degrees C) and drying at 20 degrees C. We observed clearly different stabilities under wet conditions, particularly at 4 degrees C, where infectious SFSV, HTNV, and CCHFV were detectable after 528, 96, and 15 days, respectively. All three viruses were equally sensitive to drying, as shown by drying on aluminum discs. Furthermore, HTNV and SFSV partially survived for 2 min in 30% ethanol, whereas CCHFV did not. Electron microscopy images of HTNV, SSFSV, and CCHFV stored at 37 degrees C until infectivity was lost still showed the occurrence of virions, but with abnormal shapes and densities compared to those of the nonincubated samples. In conclusion, our study points out important differences in ex vivo stability among viruses within the Bunyaviridae family. PMID- 17337568 TI - Genetic analysis of Helicobacter pylori strain populations colonizing the stomach at different times postinfection. AB - Genetic diversity of the human gastric pathogen Helicobacter pylori in an individual host has been observed; whether this diversity represents diversification of a founding strain or a mixed infection with distinct strain populations is not clear. To examine this issue, we analyzed multiple single colony isolates from two to four separate stomach biopsies of eight adult and four pediatric patients from a high-incidence Mexican population. Eleven of the 12 patients contained isolates with identical random amplified polymorphic DNA, amplified fragment length polymorphism, and vacA allele molecular footprints, whereas a single adult patient had two distinct profiles. Comparative genomic hybridization using whole-genome microarrays (array CGH) revealed variation in 24 to 67 genes in isolates from patients with similar molecular footprints. The one patient with distinct profiles contained two strain populations differing at 113 gene loci, including the cag pathogenicity island virulence genes. The two strain populations in this single host had different spatial distributions in the stomach and exhibited very limited genetic exchange. The total genetic divergence and pairwise genetic divergence between isolates from adults and isolates from children were not statistically different. We also analyzed isolates obtained 15 and 90 days after experimental infection of humans and found no evidence of genetic divergence, indicating that transmission to a new host does not induce rapid genetic changes in the bacterial population in the human stomach. Our data suggest that humans are infected with a population of closely related strains that vary at a small number of gene loci, that this population of strains may already be present when an infection is acquired, and that even during superinfection genetic exchange among distinct strains is rare. PMID- 17337570 TI - Functional complementation of the essential gene fabG1 of Mycobacterium tuberculosis by Mycobacterium smegmatis fabG but not Escherichia coli fabG. AB - Mycolic acids are a key component of the mycobacterial cell wall, providing structure and forming a major permeability barrier. In Mycobacterium tuberculosis mycolic acids are synthesized by type I and type II fatty acid synthases. One of the enzymes of the type II system is encoded by fabG1. We demonstrate here that this gene can be deleted from the M. tuberculosis chromosome only when another functional copy is provided elsewhere, showing that under normal culture conditions fabG1 is essential. FabG1 activity can be replaced by the corresponding enzyme from the closely related species Mycobacterium smegmatis but not by the enzyme from Escherichia coli. M. tuberculosis carrying FabG from M. smegmatis showed no phenotypic changes, and both the mycolic acids and cell wall permeability were unchanged. Thus, M. tuberculosis and M. smegmatis enzymes are interchangeable and do not control the lengths and types of mycolic acids synthesized. PMID- 17337569 TI - Complete nucleotide sequence of the 113-kilobase linear catabolic plasmid pAL1 of Arthrobacter nitroguajacolicus Ru61a and transcriptional analysis of genes involved in quinaldine degradation. AB - The nucleotide sequence of the linear catabolic plasmid pAL1 from the 2 methylquinoline (quinaldine)-degrading strain Arthrobacter nitroguajacolicus Ru61a comprises 112,992 bp. A total of 103 open reading frames (ORFs) were identified on pAL1, 49 of which had no annotatable function. The ORFs were assigned to the following functional groups: (i) catabolism of quinaldine and anthranilate, (ii) conjugation, and (iii) plasmid maintenance and DNA replication and repair. The genes for conversion of quinaldine to anthranilate are organized in two operons that include ORFs presumed to code for proteins involved in assembly of the quinaldine-4-oxidase holoenzyme, namely, a MobA-like putative molybdopterin cytosine dinucleotide synthase and an XdhC-like protein that could be required for insertion of the molybdenum cofactor. Genes possibly coding for enzymes involved in anthranilate degradation via 2-aminobenzoyl coenzyme A form another operon. These operons were expressed when cells were grown on quinaldine or on aromatic compounds downstream in the catabolic pathway. Single-stranded 3' overhangs of putative replication intermediates of pAL1 were predicted to form elaborate secondary structures due to palindromic and superpalindromic terminal sequences; however, the two telomeres appear to form different structures. Sequence analysis of ORFs 101 to 103 suggested that pAL1 codes for one or two putative terminal proteins, presumed to be covalently bound to the 5' termini, and a multidomain telomere-associated protein (Tap) comprising 1,707 amino acids. Even if the putative proteins encoded by ORFs 101 to 103 share motifs with the Tap and terminal proteins involved in telomere patching of Streptomyces linear replicons, their overall sequences and domain structures differ significantly. PMID- 17337571 TI - Two distinct pathways supply anthranilate as a precursor of the Pseudomonas quinolone signal. AB - Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections in immunocompromised patients and those with cystic fibrosis (CF). This gram-negative bacterium uses multiple cell-to-cell signals to control numerous cellular functions and virulence. One of these signals is 2-heptyl-3 hydroxy-4-quinolone, which is referred to as the Pseudomonas quinolone signal (PQS). This signal functions as a coinducer for a transcriptional regulator (PqsR) to positively control multiple virulence genes and its own synthesis. PQS production is required for virulence in multiple models of infection, and it has been shown to be produced in the lungs of CF patients infected by P. aeruginosa. One of the precursor compounds from which PQS is synthesized is the metabolite anthranilate. This compound can be derived from the conversion of chorismate to anthranilate by an anthranilate synthase or through the degradation of tryptophan via the anthranilate branch of the kynurenine pathway. In this study, we present data which help to define the kynurenine pathway in P. aeruginosa and show that the kynurenine pathway serves as a critical source of anthranilate for PQS synthesis. We also show that the kyn pathway genes are induced during growth with tryptophan and that they are autoregulated by kynurenine. This study provides solid foundations for the understanding of how P. aeruginosa produces the anthranilate that serves as a precursor to PQS and other 4-quinolones. PMID- 17337573 TI - Regulation of arsenate resistance in Desulfovibrio desulfuricans G20 by an arsRBCC operon and an arsC gene. AB - Desulfovibrio desulfuricans G20 grows and reduces 20 mM arsenate to arsenite in lactate-sulfate media. Sequence analysis and experimental data show that D. desulfuricans G20 has one copy of arsC and a complete arsRBCC operon in different locations within the genome. Two mutants of strain G20 with defects in arsenate resistance were generated by nitrosoguanidine mutagenesis. The arsRBCC operons were intact in both mutant strains, but each mutant had one point mutation in the single arsC gene. Mutants transformed with either the arsC1 gene or the arsRBCC operon displayed wild-type arsenate resistance, indicating that the two arsC genes were equivalently functional in the sulfate reducer. The arsC1 gene and arsRBCC operon were also cloned into Escherichia coli DH5alpha independently, with either DNA fragment conferring increased arsenate resistance. The recombinant arsRBCC operon allowed growth at up to 50 mM arsenate in LB broth. Quantitative PCR analysis of mRNA products showed that the single arsC1 was constitutively expressed, whereas the operon was under the control of the arsR repressor protein. We suggest a model for arsenate detoxification in which the product of the single arsC1 is first used to reduce arsenate. The arsenite formed is then available to induce the arsRBCC operon for more rapid arsenate detoxification. PMID- 17337572 TI - Antisense RNA modulation of alkyl hydroperoxide reductase levels in Helicobacter pylori correlates with organic peroxide toxicity but not infectivity. AB - Much of the gene content of the human gastric pathogen Helicobacter pylori ( approximately 1.7-Mb genome) is considered essential. This view is based on the completeness of metabolic pathways, infrequency of nutritional auxotrophies, and paucity of pathway redundancies typically found in bacteria with larger genomes. Thus, genetic analysis of gene function is often hampered by lethality. In the absence of controllable promoters, often used to titrate gene function, we investigated the feasibility of an antisense RNA interference strategy. To test the antisense approach, we targeted alkyl hydroperoxide reductase (AhpC), one of the most abundant proteins expressed by H. pylori and one whose function is essential for both in vitro growth and gastric colonization. Here, we show that antisense ahpC (as-ahpC) RNA expression from shuttle vector pDH37::as-ahpC achieved an approximately 72% knockdown of AhpC protein levels, which correlated with increased susceptibilities to hydrogen peroxide, cumene, and tert-butyl hydroperoxides but not with growth efficiency. Compensatory increases in catalase levels were not observed in the knockdowns. Expression of single-copy antisense constructs (expressed under the urease promoter and containing an fd phage terminator) from the rdxA locus of mouse-colonizing strain X47 achieved a 32% knockdown of AhpC protein levels (relative to wild-type X47 levels), which correlated with increased susceptibility to organic peroxides but not with mouse colonization efficiency. Our studies indicate that high levels of AhpC are not required for in vitro growth or for primary gastric colonization. Perhaps AhpC, like catalase, assumes a greater role in combating exogenous peroxides arising from lifelong chronic inflammation. These studies also demonstrate the utility of antisense RNA interference in the evaluation of gene function in H. pylori. PMID- 17337574 TI - Transcription termination within the iron transport-biosynthesis operon of Vibrio anguillarum requires an antisense RNA. AB - The iron transport-biosynthesis (ITB) operon in Vibrio anguillarum includes four genes for ferric siderophore transport, fatD, -C, -B, and -A, and two genes for siderophore biosynthesis, angR and angT. This cluster plays an important role in the virulence mechanisms of this bacterium. Despite being part of the same polycistronic mRNA, the relative levels of transcription for the fat portion and for the whole ITB message differ profoundly, the levels of the fat transcript being about 17-fold higher. Using S1 nuclease mapping, lacZ transcriptional fusions, and in vitro studies, we were able to show that the differential gene expression within the ITB operon is due to termination of transcription between the fatA and angR genes, although a few transcripts proceeded beyond the termination site to the end of this operon. This termination process requires a 427-nucleotide antisense RNA that spans the intergenic region and acts as a novel transcriptional terminator. PMID- 17337575 TI - Elongation factor Tu3 (EF-Tu3) from the kirromycin producer Streptomyces ramocissimus Is resistant to three classes of EF-Tu-specific inhibitors. AB - The antibiotic kirromycin inhibits prokaryotic protein synthesis by immobilizing elongation factor Tu (EF-Tu) on the elongating ribosome. Streptomyces ramocissimus, the producer of kirromycin, contains three tuf genes. While tuf1 and tuf2 encode kirromycin-sensitive EF-Tu species, the function of tuf3 is unknown. Here we demonstrate that EF-Tu3, in contrast to EF-Tu1 and EF-Tu2, is resistant to three classes of EF-Tu-targeted antibiotics: kirromycin, pulvomycin, and GE2270A. A mixture of EF-Tu1 and EF-Tu3 was sensitive to kirromycin and resistant to GE2270A, in agreement with the described modes of action of these antibiotics. Transcription of tuf3 was observed during exponential growth and ceased upon entry into stationary phase and therefore did not correlate with the appearance of kirromycin in stationary phase; thus, it is unlikely that EF-Tu3 functions as a resistant alternative for EF-Tu1. EF-Tu3 from Streptomyces coelicolor A3(2) was also resistant to kirromycin and GE2270A, suggesting that multiple antibiotic resistance is an intrinsic feature of EF-Tu3 species. The GE2270A-resistant character of EF-Tu3 demonstrated that this divergent elongation factor is capable of substituting for EF-Tu1 in vivo. PMID- 17337576 TI - A putative gene cluster for aminoarabinose biosynthesis is essential for Burkholderia cenocepacia viability. AB - Using a conditional mutagenesis strategy we demonstrate here that a gene cluster encoding putative aminoarabinose (Ara4N) biosynthesis enzymes is essential for the viability of Burkholderia cenocepacia. Loss of viability is associated with dramatic changes in bacterial cell morphology and ultrastructure, increased permeability to propidium iodide, and sensitivity to sodium dodecyl sulfate, suggesting a general cell envelope defect caused by the lack of Ara4N. PMID- 17337577 TI - The complete genome sequence of Bacillus thuringiensis Al Hakam. AB - Bacillus thuringiensis is an insect pathogen that is widely used as a biopesticide (E. Schnepf, N. Crickmore, J. Van Rie, D. Lereclus, J. Baum, J. Feitelson, D. R. Zeigler, and D. H. Dean, Microbiol. Mol. Biol. Rev. 62:775-806, 1998). Here we report the finished, annotated genome sequence of B. thuringiensis Al Hakam, which was collected in Iraq by the United Nations Special Commission (L. Radnedge, P. Agron, K. Hill, P. Jackson, L. Ticknor, P. Keim, and G. Andersen, Appl. Environ. Microbiol. 69:2755-2764, 2003). PMID- 17337578 TI - In vivo modulation of a DnaJ homolog, CbpA, by CbpM. AB - CbpA, an Escherichia coli DnaJ homolog, can function as a cochaperone for the DnaK/Hsp70 chaperone system, and its in vitro activity can be modulated by CbpM. We discovered that CbpM specifically inhibits the in vivo activity of CbpA, preventing it from functioning in cell growth and division. Furthermore, we have shown that CbpM interacts with CbpA in vivo during stationary phase, suggesting that the inhibition of activity is a result of the interaction. These results reveal that the activity of the E. coli DnaK system can be regulated in vivo by a specific inhibitor. PMID- 17337579 TI - HpdR is a transcriptional activator of Sinorhizobium meliloti hpdA, which encodes a herbicide-targeted 4-hydroxyphenylpyruvate dioxygenase. AB - Sinorhizobium meliloti hpdA, which encodes the herbicide target 4 hydroxyphenylpyruvate dioxygenase, is positively regulated by HpdR. Gel mobility shift and DNase I footprinting analyses revealed that HpdR binds to a region that spans two conserved direct-repeat sequences within the hpdR-hpdA intergenic space. HpdR-dependent hpdA transcription occurs in the presence of 4 hydroxyphenylpyruvate, tyrosine, and phenylalanine, as well as during starvation. PMID- 17337580 TI - A-factor and phosphate depletion signals are transmitted to the grixazone biosynthesis genes via the pathway-specific transcriptional activator GriR. AB - Grixazone (GX), which is a diffusible yellow pigment containing a phenoxazinone chromophore, is one of the secondary metabolites under the control of A-factor (2 isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) in Streptomyces griseus. GX production is also induced by phosphate starvation. The whole biosynthesis gene cluster for GX was cloned and characterized. The gene cluster consisting of 13 genes contained six transcriptional units, griT, griSR, griR, griAB, griCDEFG, and griJIH. During cultivation in a phosphate-depleted medium, the six promoters were activated in the order (i) griR, (ii) griC and griJ, and (iii) griT, griS, and griA. Disruption of griR, which encodes a SARP family transcriptional regulator, abolished the transcriptional activation of all other genes in the cluster. In addition, ectopic expression of griR from a constitutively active promoter resulted in GX overproduction even in the absence of AdpA, a key transcriptional activator in the A-factor regulatory cascade, and in the presence of phosphate at a high concentration. GriR monomers bound direct repeat sequences in the griC and griJ promoters in a cooperative manner. Therefore, the early active genes (griCDEFG and griJIH), all of which, except for griG (which encodes a transporter-like protein), encode the GX biosynthesis enzymes, were directly activated by GriR. The transcription of griR was greatly reduced in the presence of phosphate at a high concentration and was hardly detected in the absence of AdpA. These findings showed that both A-factor and phosphate depletion signals were required for griR transcription and both signals were transmitted to the GX biosynthesis genes solely via the griR promoter. PMID- 17337581 TI - Probing the essential catalytic residues and substrate affinity in the thermoactive Bacillus stearothermophilus US100 L-arabinose isomerase by site directed mutagenesis. AB - The L-arabinose isomerase (L-AI) from Bacillus stearothermophilus US100 is characterized by its high thermoactivity and catalytic efficiency. Furthermore, as opposed to the majority of l-arabinose isomerases, this enzyme requires metallic ions for its thermostability rather than for its activity. These features make US100 L-AI attractive as a template for industrial use. Based on previously solved crystal structures and sequence alignments, we identified amino acids that are putatively important for the US100 L-AI isomerization reaction. Among these, E306, E331, H348, and H447, which correspond to the suggested essential catalytic amino acids of the L-fucose isomerase and the L-arabinose isomerase from Escherichia coli, are presumed to be the active-site residues of US100 L-AI. Site-directed mutagenesis confirmed that the mutation of these residues resulted in totally inactive proteins, thus demonstrating their critical role in the enzyme activity. A homology model of US100 L-AI was constructed, and its analysis highlighted another set of residues which may be crucial for the recognition and processing of substrates; hence, these residues were subjected to mutagenesis studies. The replacement of the D308, F329, E351, and H446 amino acids with alanine seriously affected the enzyme activities, and suggestions about the roles of these residues in the catalytic mechanism are given. The mutation F279Q strongly increased the enzyme's affinity for L-fucose and decreased the affinity for L-arabinose compared to that of the wild-type enzyme, showing the implication of this amino acid in substrate recognition. PMID- 17337582 TI - Spatial patterns of DNA replication, protein synthesis, and oxygen concentration within bacterial biofilms reveal diverse physiological states. AB - It has long been suspected that microbial biofilms harbor cells in a variety of activity states, but there have been few direct experimental visualizations of this physiological heterogeneity. Spatial patterns of DNA replication and protein synthetic activity were imaged and quantified in staphylococcal biofilms using immunofluorescent detection of pulse-labeled DNA and also an inducible green fluorescent protein (GFP) construct. Stratified patterns of DNA synthetic and protein synthetic activity were observed in all three biofilm systems to which the techniques were applied. In a colony biofilm system, the dimensions of the zone of anabolism at the air interface ranged from 16 to 38 microm and corresponded with the depth of oxygen penetration measured with a microelectrode. A second zone of activity was observed along the nutrient interface of the biofilm. Much of the biofilm was anabolically inactive. Since dead cells constituted only 10% of the biofilm population, most of the inactive cells in the biofilm were still viable. Collectively, these results suggest that staphylococcal biofilms contain cells in at least four distinct states: growing aerobically, growing fermentatively, dead, and dormant. The variety of activity states represented in a biofilm may contribute to the special ecology and tolerance to antimicrobial agents of biofilms. PMID- 17337583 TI - In vitro studies of the uridylylation of the three PII protein paralogs from Rhodospirillum rubrum: the transferase activity of R. rubrum GlnD is regulated by alpha-ketoglutarate and divalent cations but not by glutamine. AB - P(II) proteins have been shown to be key players in the regulation of nitrogen fixation and ammonia assimilation in bacteria. The mode by which these proteins act as signals is by being in either a form modified by UMP or the unmodified form. The modification, as well as demodification, is catalyzed by a bifunctional enzyme encoded by the glnD gene. The regulation of this enzyme is thus of central importance. In Rhodospirillum rubrum, three P(II) paralogs have been identified. In this study, we have used purified GlnD and P(II) proteins from R. rubrum, and we show that for the uridylylation activity of R. rubrum GlnD, alpha ketoglutarate is the main signal, whereas glutamine has no effect. This is in contrast to, e.g., the Escherichia coli system. Furthermore, we show that all three P(II) proteins are uridylylated, although the efficiency is dependent on the cation present. This difference may be of importance in understanding the effects of the P(II) proteins on the different target enzymes. Furthermore, we show that the deuridylylation reaction is greatly stimulated by glutamine and that Mn(2+) is required. PMID- 17337584 TI - Characterization of Sinorhizobium meliloti triose phosphate isomerase genes. AB - A Tn5 mutant strain of Sinorhizobium meliloti with an insertion in tpiA (systematic identifier SMc01023), a putative triose phosphate isomerase (TPI) encoding gene, was isolated. The tpiA mutant grew more slowly than the wild type on rhamnose and did not grow with glycerol as a sole carbon source. The genome of S. meliloti wild-type Rm1021 contains a second predicted TPI-encoding gene, tpiB (SMc01614). We have constructed mutations and confirmed that both genes encode functional TPI enzymes. tpiA appears to be constitutively expressed and provides the primary TPI activity for central metabolism. tpiB has been shown to be required for growth with erythritol. TpiB activity is induced by growth with erythritol; however, basal levels of TpiB activity present in tpiA mutants allow for growth with gluconeogenic carbon sources. Although tpiA mutants can be complemented by tpiB, tpiA cannot substitute for mutations in tpiB with respect to erythritol catabolism. Mutations in tpiA or tpiB alone do not cause symbiotic defects; however, mutations in both tpiA and tpiB caused reduced symbiotic nitrogen fixation. PMID- 17337585 TI - Inverse regulation of biofilm formation and swarming motility by Pseudomonas aeruginosa PA14. AB - We previously reported that SadB, a protein of unknown function, is required for an early step in biofilm formation by the opportunistic pathogen Pseudomonas aeruginosa. Here we report that a mutation in sadB also results in increased swarming compared to the wild-type strain. Our data are consistent with a model in which SadB inversely regulates biofilm formation and swarming motility via its ability both to modulate flagellar reversals in a viscosity-dependent fashion and to influence the production of the Pel exopolysaccharide. We also show that SadB is required to properly modulate flagellar reversal rates via chemotaxis cluster IV (CheIV cluster). Mutational analyses of two components of the CheIV cluster, the methyl-accepting chemotaxis protein PilJ and the PilJ demethylase ChpB, support a model wherein this chemotaxis cluster participates in the inverse regulation of biofilm formation and swarming motility. Epistasis analysis indicates that SadB functions upstream of the CheIV cluster. We propose that P. aeruginosa utilizes a SadB-dependent, chemotaxis-like regulatory pathway to inversely regulate two key surface behaviors, biofilm formation and swarming motility. PMID- 17337586 TI - Identification of novel Escherichia coli ribosome-associated proteins using isobaric tags and multidimensional protein identification techniques. AB - Biogenesis of the large ribosomal subunit requires the coordinate assembly of two rRNAs and 33 ribosomal proteins. In vivo, additional ribosome assembly factors, such as helicases, GTPases, pseudouridine synthetases, and methyltransferases, are also critical for ribosome assembly. To identify novel ribosome-associated proteins, we used a proteomic approach (isotope tagging for relative and absolute quantitation) that allows for semiquantitation of proteins from complex protein mixtures. Ribosomal subunits were separated by sucrose density centrifugation, and the relevant fractions were pooled and analyzed. The utility and reproducibility of the technique were validated via a double duplex labeling method. Next, we examined proteins from 30S, 50S, and translating ribosomes isolated at both 16 degrees C and 37 degrees C. We show that the use of isobaric tags to quantify proteins from these particles is an excellent predictor of the particles with which the proteins associate. Moreover, in addition to bona fide ribosomal proteins, additional proteins that comigrated with different ribosomal particles were detected, including both known ribosomal assembly factors and unknown proteins. The ribosome association of several of these proteins, as well as others predicted to be associated with ribosomes, was verified by immunoblotting. Curiously, deletion mutants for the majority of these ribosome associated proteins had little effect on cell growth or on the polyribosome profiles. PMID- 17337587 TI - A pair of highly conserved two-component systems participates in the regulation of the hypervariable FIR proteins in different Legionella species. AB - Legionella pneumophila and other pathogenic Legionella species multiply inside protozoa and human macrophages by using the Icm/Dot type IV secretion system. The IcmQ protein, which possesses pore-forming activity, and IcmR, which functions as its chaperone, are two essential components of this system. It was previously shown that in 29 Legionella species, a large hypervariable-gene family (fir genes) is located upstream from a conserved icmQ gene, but although nonhomologous, the FIR proteins were found to function similarly together with their corresponding IcmQ proteins. Alignment of the regulatory regions of 29 fir genes revealed that they can be divided into three regulatory groups; the first group contains a binding site for the CpxR response regulator, which was previously shown to regulate the L. pneumophila fir gene (icmR); the second group, which includes most of the fir genes, contains the CpxR binding site and an additional regulatory element that was identified here as a PmrA binding site; and the third group contains only the PmrA binding site. Analysis of the regulatory region of two fir genes, which included substitutions in the CpxR and PmrA consensus sequences, a controlled expression system, as well as examination of direct binding with mobility shift assays, revealed that both CpxR and PmrA positively regulate the expression of the fir genes that contain both regulatory elements. The change in the regulation of the fir genes that occurred during the course of evolution might be required for the adaptation of the different Legionella species to their specific environmental hosts. PMID- 17337589 TI - Parasympathetic reactivation after repeated sprint exercise. AB - The purpose of this study was to examine the effects of muscular power engagement, anaerobic participation, aerobic power level, and energy expenditure on postexercise parasympathetic reactivation. We compared the response of heart rate (HR) after repeated sprinting with that of exercise sessions of comparable net energy expenditure and anaerobic energy contribution. Fifteen moderately trained athletes performed 1) 18 maximal all-out 15-m sprints interspersed with 17 s of passive recovery (RS), 2) a moderate isocaloric continuous exercise session (MC) at a level of mean oxygen uptake similar to that of the RS trial, and 3) a high-intensity intermittent exercise session (HI) conducted at a level of anaerobic energy expenditure similar to that of the RS trial. Subjects were immediately seated after the exercise trials, and beat-to-beat HR was recorded for 10 min. Parasympathetic reactivation was evaluated through 1) immediate postexercise HR recovery, 2) the time course of the root mean square for the successive R-R interval difference between successive 30-s segments (RMSSD(30s)) and 3) HR variability vagal-related indexes calculated for the last 5-min stationary period of recovery. RMSSD(30s) increased during the 10-min period after the MC trial, whereas RMSSD(30s) remained depressed after both the RS and HI trials. Parasympathetic reactivation indexes were similar for the RS and HI trials but lower than for the MC trial (P < 0.001). When data of the three exercise trials were considered together, only anaerobic contribution was related to HR trial-derived indexes. Parasympathetic reactivation is highly impaired after RS exercise and appears to be mainly related to anaerobic process participation. PMID- 17337588 TI - Problems of basing patient recruitment for primary care studies on routine laboratory submissions. AB - BACKGROUND: Use of routine urine submission rates for estimation of patient enrollment in primary care studies of acute urinary symptoms may overestimate patient recruitment rate. AIMS: To compare the rates of submission of urines and significant bacteriuria from patients presenting with acute urinary symptoms in study general practices to routine microbiology laboratory urines. METHODS: Routine laboratory urine submissions were determined by counting all mid-stream urine specimens submitted to the laboratory from 12 large general practitioner (GP) practices served by Gloucester and Southmead microbiology departments over two years (2000-02). Urine specimens were requested from all patients with acute urinary symptoms referred at research nurse practice visits over the same time period. The annual study urine submission was calculated using the ratio of the number of nurse practice visits to the annual number of possible consulting sessions. Significant bacteriuria was defined as a urine growing a single organism reported as >10(5) colony forming units/ml. Rates per 1000 patients were calculated using practice population data. RESULTS: The urine submission rate from study patients with acute urinary symptoms was one-third the routine urine submission rate from the same practices. The significant bacteriuria rate attained from the study was less than half the routine significant bacteriuria rate. CONCLUSION: Two-thirds of routine urine samples submitted by GPs are probably not for the investigation of acute urinary symptoms. Basing consultation sample size power calculations for primary care studies or sentinel practice based surveillance in urinary tract infection on routine laboratory submissions is unreliable and will lead to significant overestimation of recruitment rate. PMID- 17337590 TI - Calf venous compliance in multiple system atrophy. AB - In multiple system atrophy (MSA), increased venous compliance with excessive venous pooling is assumed to be a major contributor to orthostatic hypotension (OH); however, venous compliance has never been assessed in MSA patients. We evaluated the severity and distribution of adrenergic, cardiovagal, and sudomotor failure in 11 patients with probable MSA, 14 age- and sex-matched control subjects, and 8 patients with Parkinson's disease (PD) but not OH. Calf venous compliance, venous filling, and capillary filtration were measured using calf plethysmography. The response to the directly acting alpha-adrenergic stimulation (10 mg midodrine) on calf venous compliance was additionally evaluated. Contrary to our hypothesis, pressure-volume curves in the legs of MSA patients were flatter than in PD patients (P < 0.05) or controls (P < 0.001); this indicated reduced calf venous compliance in MSA. The MSA group had reduced venous filling compared with control (P < 0.001) or PD subjects (P < 0.001) but had a normal capillary filtration rate (P = 0.73). Direct alpha-adrenergic stimulation resulted in a slight but significant reduction of calf venous compliance in controls (P = 0.001) and PD subjects (P < 0.001) but not in the MSA group. The compliance change in MSA significantly regressed with autonomic failure (composite autonomic severity scale, r(2) = 0.56) but not with parkinsonism (Unified MSA Rating Scale, r(2) = 0.12). Our data indicate that MSA patients with chronic OH have reduced, rather than increased, venous compliance in the lower leg. We postulate that chronic venous distension that is associated with OH results in structural remodeling of veins, leading to reduced compliance, a change which may protect patients against orthostatic stress. PMID- 17337591 TI - TNF-alpha downregulates transient outward potassium current in rat ventricular myocytes through iNOS overexpression and oxidant species generation. AB - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in the pathogenesis of heart failure. Prolongation of the action potential duration and downregulation of several K(+) currents might participate in the genesis of arrhythmias associated with chronic heart failure. Little information is available related to the mechanism by which TNF-alpha modulates cardiac K(+) channels. The present study analyzes the effect of TNF-alpha on the transient outward K(+) current (I(to)) in rat ventricular myocytes, using the whole cell patch-clamp technique. We found that TNF-alpha is able to induce a significant reduction of I(to) density, modifies its inactivation, and downregulates the Kv4.2 protein expression, while calcium current density is not affected. We have also demonstrated that the reduction of I(to) density induced by TNF-alpha was prevented by the selective inducible nitric oxide synthase (iNOS) inhibitor 1400-W, the protein synthesis inhibitor cycloheximide, the antioxidant tocopherol, and the superoxide dismutase mimetic manganese(III) tetrakis (4-benzoic acid) porphyrin. In addition, a reduced I(to) density was recorded in ventricular myocytes exposed to peroxynitrite, supporting a possible participation of this oxidant in the effects of TNF-alpha on I(to). We conclude that TNF-alpha exposure, through iNOS induction and generation of oxidant species, promotes electrophysiological changes (decreased I(to) and action potential duration prolongation) in rat ventricular myocytes, providing new insights into how cytokines modulate K(+) channels in the heart. PMID- 17337592 TI - Hypoxic preconditioning protects human brain endothelium from ischemic apoptosis by Akt-dependent survivin activation. AB - Preconditioning-induced ischemic tolerance is well documented in the brain, but cell-specific responses and mechanisms require further elucidation. The aim of this study was to develop an in vitro model of ischemic tolerance in human brain microvascular endothelial cells (HBMECs) and to examine the roles of phosphatidylinositol 3-kinase (PI3-kinase)/Akt and the inhibitor-of- apoptosis protein, survivin, in the ability of hypoxic preconditioning (HP) to protect endothelium from apoptotic cell death. Cultured HBMECs were subjected to HP, followed 16 h later by complete oxygen and glucose deprivation (OGD) for 8 h; cell viability was quantified at 20 h of reoxygenation (RO) by the 3-(4,5 dimethylthiazol)-2,5-diphenyltetrazolium bromide assay. HBMECs were examined at various times after HP or OGD/RO using immunoblotting and confocal laser scanning immunofluorescence microscopy for appearance of apoptotic markers and expression of phosphorylated (p)-Akt and p-survivin. Causal evidence for the participation of the PI3-kinase/Akt pathway in HP-induced protection and p-survivin upregulation was assessed by the PI3-kinase inhibitor LY-294002. HP significantly reduced OGD/RO-induced injury by 50% and also significantly reduced the OGD induced translocation of apoptosis-inducing factor (AIF) from mitochondria to nucleus and the concomitant cleavage of poly(ADP-ribose) polymerase-1 (PARP-1). PI3-kinase inhibition blocked HP-induced increases in Akt phosphorylation, reversed the effects of HP on OGD-induced AIF translocation and PARP-1 cleavage, blocked HP-induced survivin phosphorylation, and ultimately attenuated HP-induced protection of HBMECs from OGD. Thus HP promotes an antiapoptotic phenotype in HBMECs, in part by activating survivin via the PI3-kinase/Akt pathway. Survivin and other phosphorylation products of p-Akt may be therapeutic targets to protect cerebrovascular endothelium from apoptotic injury following cerebral ischemia. PMID- 17337593 TI - Sphingosine-1-phosphate receptor expression in cardiac fibroblasts is modulated by in vitro culture conditions. AB - The bioactive molecule sphingosine-1-phosphate (S1P) binds with high affinity to five recognized receptors (S1P(1-5)) to affect various tissues, including cellular responses of cardiac fibroblasts (CFbs) and myocytes. CFbs are essential components of myocardium, and detailed study of their cell signaling and physiology is required for a number of emerging disciplines. Meaningful studies on CFbs, however, necessitate methods for selective, reproducible cell isolations. Macrophages reside within normal cardiac tissues and often are isolated with CFbs. A protocol was therefore developed that significantly reduces macrophage levels and utilizes more CFb-specific markers (discoidin domain receptor-2) instead of, or in addition to, more commonly used cytoskeletal markers. Our results demonstrate that primary isolated, purified CFbs express predominantly S1P(1-3); however, the relative levels of these receptor subtypes are modulated with time and by culture conditions. In coculture experiments, macrophages altered CFb S1P receptor levels relative to controls. Further investigations using known macrophage-secreted factors showed that S1P and H(2)O(2) had minimal effects on CFb S1P(1-3) expression, whereas transforming growth factor-beta1, TNF-alpha, and PDGF-BB significantly altered all S1P receptor subtypes. Lowering FBS concentrations from 10% to 0.1% increased S1P(2), whereas supplementation with either PDGF-BB or Rho-associated protein kinase inhibitor Y-27632 significantly elevated S1P(3) levels. S1P(2) and S1P(3) receptor levels are known to regulate cell migration. Using cells isolated from either normal or S1P(3)-null mice, we demonstrate that S1P(3) is important and necessary for CFb migration. These results highlight the importance of demonstrating CFb culture purity in functional studies of S1P and also identify conditions that modulate S1P receptor expression in CFbs. PMID- 17337594 TI - Human recombinant erythropoietin protects the striated muscle microcirculation of the dorsal skinfold from postischemic injury in mice. AB - Erythropoietin (EPO) has been proposed as a novel cytoprotectant in ischemia reperfusion (I/R) injury of the brain, heart, and kidney. However, whether EPO exerts its protection by prevention of postischemic microcirculatory deterioration is unknown. We have investigated the effect of EPO on I/R-induced microcirculatory dysfunctions. We used the mouse dorsal skinfold chamber preparation to study nutritive microcirculation and leukocyte-endothelial cell interaction in striated muscle of the dorsal skinfold by in vivo fluorescence microscopy before 3 h of ischemia and during 5 days of reperfusion. Animals were pretreated with EPO (5,000 U/kg body wt) 1 or 24 h before ischemia. Vehicle treated I/R-injured animals served as controls. Additional animals underwent sham operation only or were pretreated with EPO but not subjected to I/R. I/R significantly (P < 0.05) reduced functional capillary density, increased microvascular permeability, and enhanced venular leukocyte-endothelial cell interaction during early reperfusion. These findings were associated with pronounced (P < 0.05) arteriolar constriction and diminution of blood flow during late reperfusion. Pretreatment with EPO induced EPO receptor and endothelial nitric oxide synthase expression at 6 h of reperfusion (P < 0.05). In parallel, EPO significantly (P < 0.05) reduced capillary perfusion failure and microvascular hyperpermeability during early reperfusion and arteriolar constriction and flow during late reperfusion. EPO pretreatment substantially (P < 0.05) diminished I/R-induced leukocytic inflammation by reducing the number of rolling and firmly adhering leukocytes in postcapillary venules. EPO applied 1 h before ischemia induced angiogenic budding and sprouting at 1 and 3 days of reperfusion and formation of new capillary networks at 5 days of reperfusion. Thus our study demonstrates for the first time that EPO effectively attenuates I/R injury by preserving nutritive perfusion, reducing leukocytic inflammation, and inducing new vessel formation. PMID- 17337595 TI - Vascular-derived artemin: a determinant of vascular sympathetic innervation? AB - Vascular sympathetic innervation is an important determinant of blood pressure and blood flow. The mechanisms that determine vascular sympathetic innervation are not well understood. The present study tests the hypothesis that vascular derived artemin promotes the development of sympathetic innervation to blood vessels by promoting sympathetic axon growth. RT-PCR and Western analyses indicate that artemin is expressed by cultured vascular smooth muscle and arteries, and artemin coreceptors, glial cell-derived neurotrophic factor family receptor alpha3 and ret, are expressed by postganglionic sympathetic neurons. The effects of artemin on axon growth were assessed on explants of neonatal rat sympathetic ganglia. In the presence, but not in the absence, of nerve growth factor, exogenous artemin stimulated neurite growth. Femoral arteries (FA) from adult rats contain artemin, and these arteries stimulated sympathetic neurite growth. Growth in the presence of FA was 92.2 +/- 11.9 mm, and that in the absence of FA was 26.3 +/- 5.4 mm (P < 0.05). FA stimulation of axon growth was reduced by an antibody that neutralized the activity of artemin (P < 0.05). These data indicate that artemin is expressed in arteries, and its receptors are expressed and functional in the postganglionic sympathetic neurons that innervate them. This suggests that artemin may be a determinant of vascular sympathetic innervation. PMID- 17337596 TI - The protein kinase C pathway mediates cardioprotection induced by cardiac specific overexpression of fibroblast growth factor-2. AB - Elucidation of protective mechanisms against ischemia-reperfusion injury is vital to the advancement of therapeutics for ischemic heart disease. Our laboratory has previously shown that cardiac-specific overexpression of fibroblast growth factor 2 (FGF2) results in increased recovery of contractile function and decreased infarct size following ischemia-reperfusion injury and has established a role for the mitogen-activated protein kinase (MAPK) signaling cascade in the cardioprotective effect of FGF2. We now show an additional role for the protein kinase C (PKC) signaling cascade in the mediation of FGF2-induced cardioprotection. Overexpression of FGF2 (FGF2 Tg) in the heart resulted in decreased translocation of PKC-delta but had no effect on PKC-alpha, -epsilon, or -zeta. In addition, multiple alterations in PKC isoform translocation occur during ischemia-reperfusion injury in FGF2 Tg hearts as assessed by Western blot analysis and confocal immunofluorescent microscopy. Treatment of FGF2 Tg and nontransgenic (NTg) hearts with the PKC inhibitor bisindolylmaleimide (1 micromol/l) revealed the necessity of PKC signaling for FGF2-induced reduction of contractile dysfunction and myocardial infarct size following ischemia reperfusion injury. Western blot analysis of FGF2 Tg and NTg hearts subjected to ischemia-reperfusion injury in the presence of a PKC pathway inhibitor (bisindolylmaleimide, 1 micromol/l), an mitogen/extracellular signal-regulated kinase/extracellular signal-regulated kinase (MEK/ERK) pathway inhibitor (U-0126, 2.5 micromol/l), or a p38 pathway inhibitor (SB-203580, 2 micromol/l) revealed a complicated signaling network between the PKC and MAPK signaling cascades that may participate in FGF2-induced cardioprotection. Together, these data suggest that FGF2-induced cardioprotection is mediated via a PKC-dependent pathway and that the PKC and MAPK signaling cascades are integrally connected downstream of FGF2. PMID- 17337597 TI - Restoration of CREB function is linked to completion and stabilization of adaptive cardiac hypertrophy in response to exercise. AB - Potential regulation of two factors linked to physiological outcomes with left ventricular (LV) hypertrophy, resistance to apoptosis, and matching of metabolic capacity, by the transcription factor cyclic-nucleotide regulatory element binding protein (CREB), was examined in the two models of physiological LV hypertrophy: involuntary treadmill running of female Sprague-Dawley rats and voluntary exercise wheel running in female C57Bl/6 mice. Comparative studies were performed in the models of pathological LV hypertrophy and failure: the spontaneously hypertension heart failure (SHHF) rat and the hypertrophic cardiomyopathy (HCM) transgenic mouse, a model of familial idiopathic cardiomyopathy. Activating CREB serine-133 phosphorylation was decreased early in remodeling in response to both physiological (decreased 50-80%) and pathological (decreased 60-80%) hypertrophic stimuli. Restoration of LV CREB phosphorylation occurred concurrent with completion of physiological hypertrophy (94% of sedentary control), but remained decreased (by 90%) during pathological hypertrophy. In all models of hypertrophy, CREB phosphorylation/activation demonstrated strong positive correlations with 1) expression of the anti apoptotic protein bcl-2 (a CREB-dependent gene) and subsequent reductions in the activation of caspase 9 and caspase 3; 2) expression of peroxisome proliferator activated receptor-gamma coactivator-1 (PGC-1; a major regulator of mitochondrial content and respiratory capacity), and 3) LV mitochondrial respiratory rates and mitochondrial protein content. Exercise-induced increases in LV mitochondrial respiratory capacity were commensurate with increases observed in LV mass, as previously reported in the literature. Exercise training of SHHF rats and HCM mice in LV failure improved cardiac phenotype, increased CREB activation (31 and 118%, respectively), increased bcl-2 content, improved apoptotic status, and enhanced PGC-1 content and mitochondrial gene expression. Adenovirus-mediated expression of constitutively active CREB in neonatal rat cardiac recapitulated exercise-induced upregulation of PGC-1 content and mitochondrial oxidative gene expression. These data support a model wherein CREB contributes to physiological hypertrophy by enhancing expression of genes important for efficient oxidative capacity and resistance to apoptosis. PMID- 17337598 TI - Hic-5 promotes endothelial cell migration to lysophosphatidic acid. AB - Endothelial cell migration is critical for proper blood vessel development. Signals from growth factors and matrix proteins are integrated through focal adhesion proteins to alter cell migration. Hydrogen peroxide-inducible clone 5 (Hic-5), a paxillin family member, is enriched in the focal adhesions in bovine pulmonary artery endothelial (BPAE) cells, which migrate to lysophosphatidic acid (LPA) on denatured collagen. In this study, we investigate the role of Hic-5 in LPA-stimulated endothelial cell migration. LPA recruits Hic-5 to the focal adhesions and to the pseudopodia in BPAE cells plated on collagen, suggesting that recruitment of Hic-5 to focal adhesions is associated with endothelial cell migration. Knockdown of endogenous Hic-5 significantly decreases migration toward LPA, confirming involvement of Hic-5 in migration. To address the role of Hic-5 in endothelial cell migration, we exogenously expressed wild-type (WT) Hic-5 and green fluorescent protein Hic-5 C369A/C372A (LIM3 mutant) constructs in BPAE cells. WT Hic-5 expression increases chemotaxis of BPAE cells to LPA, whereas migration toward LPA of the green fluorescent protein Hic-5 C369A/C372A expressing cells is similar to that shown in vector control cells. Additionally, ERK phosphorylation is enhanced in the presence of LPA in WT Hic-5 cells. A pharmacological inhibitor of MEK activity inhibits LPA-stimulated WT Hic-5 cell migration and ERK phosphorylation, suggesting Hic-5 enhances migration via MEK activation of ERK. Together, these studies indicate that Hic-5, a focal adhesion protein in endothelial cells, is recruited to the pseudopodia in the presence of LPA and enhances migration. PMID- 17337600 TI - Dual cardiac contractile effects of the alpha2-AMPK deletion in low-flow ischemia and reperfusion. AB - Because the question "is AMP-activated protein kinase (AMPK) alpha(2)-isoform a friend or a foe in the protection of the myocardium against ischemia-reperfusion injury?" is still in debate, we studied the functional consequence of its deletion on the contractility, the energetics, and the respiration of the isolated perfused heart and characterized the response to low-flow ischemia and reperfusion with glucose and pyruvate as substrates. alpha(2)-AMPK deletion did not affect basal contractility, respiration, and high-energy phosphate contents but induced a twofold reduction in glycogen content and a threefold reduction in glucose uptake. Low-flow ischemia increased AMPK phosphorylation and stimulated glucose uptake and phosphorylation in both alpha(2)-knockout (alpha(2)-KO) and wild-type (WT) groups. The high sensitivity of alpha(2)-KO to the development of ischemic contracture was attributed to the constitutive impairment in glucose transport and glycogen content and not to a perturbation of the energy transfer by creatine kinase (CK). The functional coupling of MM-CK to myofibrillar ATPase and the CK fluxes were indeed similar in alpha(2)-KO and WT. Low-flow ischemia impaired CK flux by 50% in both strains, showing that alpha(2)-AMPK does not control CK activity. Despite the higher sensitivity to contracture, the postischemic contractility recovered to similar levels in both alpha(2)-KO and WT in the absence of fatty acids. In their presence, alpha(2)-AMPK deletion also accelerated the contracture but delayed postischemic contractile recovery. In conclusion, alpha(2)-AMPK is required for a normal glucose uptake and glycogen content, which protects the heart from the development of the ischemic contracture, but not for contractile recovery in the absence of fatty acids. PMID- 17337599 TI - Cardiac-restricted angiotensin-converting enzyme overexpression causes conduction defects and connexin dysregulation. AB - Renin-angiotensin (RAS) system activation is associated with an increased risk of sudden death. Previously, we used cardiac-restricted angiotensin-converting enzyme (ACE) overexpression to construct a mouse model of RAS activation. These ACE 8/8 mice die prematurely and abruptly. Here, we have investigated cardiac electrophysiological abnormalities that may contribute to early mortality in this model. In ACE 8/8 mice, surface ECG voltages are reduced. Intracardiac electrograms showed atrial and ventricular potential amplitudes of 11% and 24% compared with matched wild-type (WT) controls. The atrioventricular (AV), atrio Hisian (AH), and Hisian-ventricular (HV) intervals were prolonged 2.8-, 2.6-, and 3.9-fold, respectively, in ACE 8/8 vs. WT mice. Various degrees of AV nodal block were present only in ACE 8/8 mice. Intracardiac electrophysiology studies demonstrated that WT and heterozygote (HZ) mice were noninducible, whereas 83% of ACE 8/8 mice demonstrated ventricular tachycardia with burst pacing. Atrial connexin 40 (Cx40) and connexin 43 (Cx43) protein levels, ventricular Cx43 protein level, atrial and ventricular Cx40 mRNA abundances, ventricular Cx43 mRNA abundance, and atrial and ventricular cardiac Na(+) channel (Scn5a) mRNA abundances were reduced in ACE 8/8 compared with WT mice. ACE 8/8 mice demonstrated ventricular Cx43 dephosphorylation. Atrial and ventricular L-type Ca(2+) channel, Kv4.2 K(+) channel alpha-subunit, and Cx45 mRNA abundances and the peak ventricular Na(+) current did not differ between the groups. In isolated heart preparations, a connexin blocker, 1-heptanol (0.5 mM), produced an electrophysiological phenotype similar to that seen in ACE 8/8 mice. Therefore, cardiac-specific ACE overexpression resulted in changes in connexins consistent with the phenotype of low-voltage electrical activity, conduction defects, and induced ventricular arrhythmia. These results may help explain the increased risk of arrhythmia in states of RAS activation such as heart failure. PMID- 17337601 TI - Caveolin-1 and caveolin-3 regulate Ca2+ homeostasis of single smooth muscle cells from rat cerebral resistance arteries. AB - The role of caveolins, signature proteins of caveolae, in arterial Ca(2+) regulation is unknown. We investigated modulation of Ca(2+) homeostasis by caveolin-1 and caveolin-3 using smooth muscle cells from rat cerebral resistance arteries. Membrane current and Ca(2+) transients were simultaneously measured with voltage-clamped single cells. Membrane depolarization triggered Ca(2+) current and increased intracellular Ca(2+) concentration ([Ca(2+)](i)). After repolarization, elevated [Ca(2+)](i) returned to the resting level. Ca(2+) removal rate was determined from the declining phase of the Ca(2+) transient. Application of caveolin-1 antibody or caveolin-1 scaffolding domain peptide, corresponding to amino acid residues 82-101 of caveolin-1, significantly slowed Ca(2+) removal rate at a measured [Ca(2+)](i) of 250 nM, with little effect at a measured [Ca(2+)](i) of 600 nM. Application of caveolin-3 antibody or caveolin-3 scaffolding domain peptide, corresponding to amino acid residues 55-74 of caveolin-3, also significantly slowed Ca(2+) removal rate at a measured [Ca(2+)](i) of 250 nM, with little effect at a measured [Ca(2+)](i) of 600 nM. Likewise, application of calmodulin inhibitory peptide, autocamtide-2-related inhibitory peptide, and cyclosporine A, inhibitors for calmodulin, Ca(2+)/calmodulin-dependent protein kinase II, and calcineurin, also significantly inhibited Ca(2+) removal rate at a measured [Ca(2+)](i) of 250 nM but not at 600 nM. Application of cyclopiazonic acid, a sarcoplasmic reticulum Ca(2+) ATPase inhibitor, also significantly inhibited Ca(2+) removal rate at a measured [Ca(2+)](i) of 250 nM but not at 600 nM. Our results suggest that caveolin-1 and caveolin-3 are important in Ca(2+) removal of resistance artery smooth muscle cells. PMID- 17337602 TI - Exercise training enhances flow-induced vasodilation in skeletal muscle resistance arteries of aged rats: role of PGI2 and nitric oxide. AB - Flow-induced vasodilation is attenuated with old age in rat skeletal muscle arterioles. The purpose of this study was to determine whether diminished cyclooxygenase (COX) signaling contributes to the age-induced attenuation of flow induced vasodilation in gastrocnemius muscle arterioles and to determine whether, and through which mechanism(s), exercise training restores this deficit in old rats. Fischer 344 rats (3 and 22 mo old) were assigned to a sedentary or exercise trained group. First-order arterioles were isolated from the gastrocnemius muscles, cannulated, and pressurized to 70 cm H(2)O. Diameter changes were determined in response to graded increases in intraluminal flow in the presence and absence of nitric oxide synthase (NOS) inhibition [10(-5) M N(G)-nitro-L arginine methyl ester (L-NAME)], COX inhibition (10(-5) M indomethacin), or combination NOS (10(-5) M L-NAME) plus COX (10(-5) M indomethacin) inhibition. Aging reduced flow-induced vasodilation in gastrocnemius muscle arterioles. Exercise training restored responsiveness to flow in arterioles of aged rats and enhanced flow-induced vasodilation in arterioles from young rats. L-NAME inhibition of flow-induced vasodilation was greater in arterioles from old rats compared with those from young rats and was increased after exercise training in arterioles from both young and old rats. Although the indomethacin-sensitive portion of flow-induced dilation was not altered by age or training, both COX-1 mRNA expression and PGI(2) production increased with training in arterioles from old rats. These data demonstrate that exercise training restores flow-induced vasodilation in gastrocnemius muscle arterioles from old rats and enhances flow induced vasodilation in gastrocnemius muscle arterioles from young rats. In arterioles from both old and young rats, the exercise training-induced enhancement of flow-induced dilation occurs primarily through a NOS mechanism. PMID- 17337603 TI - ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K+. AB - ACh-induced endothelium-dependent relaxation in rabbit small mesenteric arteries is resistant to N-nitro-L-arginine (L-NA) and indomethacin but sensitive to high K+, indicating the relaxations are mediated by endothelium-derived hyperpolarizing factors (EDHFs). The identity of the EDHFs in this vascular bed remains undefined. Small mesenteric arteries pretreated with L-NA and indomethacin were contracted with phenylephrine. ACh (10(-10) to 10(-6) M) caused concentration-dependent relaxations that were shifted to the right by lipoxygenase inhibition and the Ca(2+)-activated K+ channel inhibitors apamin (100 nM) or charybdotoxin (100 nM) and eliminated by the combination of apamin plus charybdotoxin. Relaxations to ACh were also blocked by a combination of barium (200 microM) and apamin but not barium plus charybdotoxin. Addition of K+ (10.9 mM final concentration) to the preconstricted arteries elicited small relaxations. K+ addition before ACh restored the charybdotoxin-sensitive component of relaxations to ACh. K+ (10.9 mM) also relaxed endothelium-denuded arteries, and the relaxations were inhibited by barium but not by charybdotoxin and apamin. With the use of whole cell patch-clamp analysis, ACh (10(-7) M) stimulated voltage-dependent outward K+ current from endothelial cells, which was inhibited by charybdotoxin, indicating K+ efflux. Arachidonic acid (10(-7) to 10( 4) M) induced concentration-related relaxations that were inhibited by apamin but not by charybdotoxin and barium. Addition of arachidonic acid after K+ (10.9 mM) resulted in more potent relaxations to arachidonic acid compared with control without K+ (5.9 mM). These findings suggest that, in rabbit mesenteric arteries, ACh-induced, L-NA- and indomethacin-resistant relaxation is mediated by endothelial cell K+ efflux and arachidonic acid metabolites, and a synergism exists between these two separate mechanisms. PMID- 17337604 TI - Providing high-quality research training for veterinary pathologists in Europe. AB - Despite their key role in a wide range of fields relating to animal and public health, there is currently a lack of veterinary pathologists in Europe. In 1999, to help address the problem, the European College of Veterinary Pathologists (ECVP) and the European Society of Veterinary Pathology (ESVP) established a joint Education Committee. In this Special Article, Professor Anja Kipar and colleagues, all members of the committee, describe the ECVP/ESVP Summer Schools in Veterinary Pathology programme, which aims to provide high-quality research training for veterinary pathologists from all over Europe and beyond. PMID- 17337606 TI - Treatment of spontaneous pyometra in 22 bitches with a combination of cabergoline and cloprostenol. AB - Twenty-two bitches with ultrasonographically diagnosed spontaneous pyometra were treated with a combination of 5 microg/kg cabergoline per day and 5 mug/kg cloprostenol every third day, and potentiated sulphonamide twice a day. Bitches with either open-cervix or closed-cervix pyometra showed a rapid clinical improvement, associated with a reduction in plasma progesterone concentration, increased vulval discharge and a reduction in the diameter of the uterus. The haematological profiles of 21 of the bitches returned to normal within six days of treatment, and their biochemical profiles returned to normal within nine days; 19 of the bitches were managed successfully by a 10-day period of treatment. Two bitches required a further three days of treatment, and in one bitch with a partial uterine torsion the treatment was not successful. Adverse effects of the treatment were limited to the 60 minutes immediately after the administration of prostaglandin, and included retching, vomiting, mild abdominal straining, diarrhoea and panting. The incidence of adverse effects was reduced after each successive dose of prostaglandin. Eleven of the 21 successfully treated bitches were mated at the next oestrus, and seven became pregnant; their litters were smaller than the published breed averages. In four of the bitches the pyometra recurred after the next oestrus. PMID- 17337605 TI - National intervention study of mastitis control in dairy herds in England and Wales. AB - An intervention study was carried out on 52 dairy farms in England and Wales to determine whether the implementation of a well-specified mastitis control plan in herds with an incidence of clinical mastitis of more than 35 cases per 100 cows per year would reduce the incidence of clinical mastitis, and also reduce the incidence of increases in the somatic cell counts of individual cows. A clearly defined plan for the diagnosis and control of mastitis was developed by two veterinary specialists from the research literature. The herds were randomly allocated to receive the plan either at the start of the study (intervention herds) or after one year (control herds). Data on mastitis management and the farm environment were collected during farm visits. After one year there was a significant 22 per cent reduction in the proportion of cows affected with clinical mastitis on the intervention farms compared with the control farms. There were also significant reductions of approximately 20 per cent in the incidence of clinical mastitis and in the occurrence of increases in the somatic cell counts of individual cows from below, to above 200,000 cells/ml. PMID- 17337607 TI - Fatal enterocolitis in harbour seals (Phoca vitulina) caused by infection with Eimeria phocae. AB - Coccidiosis due to Eimeria phocae infection has been described in harbour seals (Phoca vitulina) from the western Atlantic population, but not in any detail in seals from the eastern Atlantic population. This paper describes fatal enterocolitis due to E phocae infection in three juvenile harbour seals at a rehabilitation centre in the Netherlands in July 2003. The clinical signs were lethargy, bloody faeces, and intermittent convulsions and muscle tremors just before they died; the nervous signs resembled those of nervous coccidiosis in calves. The main pathological finding was severe, diffuse, haemorrhagic enterocolitis; there were diffuse inflammatory changes in the lamina propria of the jejunal, ileal, caecal and colonic mucosa that were associated with the presence of the sexual stages and oocysts of a coccidian species identified as E phocae. A retrospective microscopical examination of intestinal tissues from 113 harbour seals that had died between 1999 and 2004 revealed one seal that was positive for E phocae. PMID- 17337608 TI - Rabies in an Israeli zoological garden. PMID- 17337609 TI - Spina bifida in broiler chicken embryos. PMID- 17337610 TI - Treatment of recurrent luxation of the shoulder in an alpaca. PMID- 17337611 TI - Suspected congenital generalised tuberculosis in a newborn calf. PMID- 17337612 TI - Serotonin toxicity in dogs. PMID- 17337613 TI - Total knee replacement for dogs. PMID- 17337614 TI - National mastitis control. PMID- 17337615 TI - Avian influenza outbreak. PMID- 17337616 TI - Supporting recent graduates. PMID- 17337618 TI - Change and continuity. PMID- 17337617 TI - Cleft lip with or without cleft palate: implication of the heavy chain of non muscle myosin IIA. AB - Non-syndromic cleft lip with or without palate (CL/P) is one of the most common malformations among live births, but most of the genetic components and environmental factors involved remain to be identified. Among the different causes, MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA, was considered a potential candidate, because it was found to be abundantly and specifically expressed in epithelial cells of palatal shelves before fusion. After fusion, its expression level was shown to decrease and to become limited to epithelial triangles before disappearing, as fusion is completed. To determine whether MYH9 plays a role in CL/P aetiology, a family-based association analysis was performed in 218 case/parent triads using single-nucleotide polymorphism (SNP) markers. Pairwise and multilocus haplotype analyses identified linkage disequilibrium between polymorphism alleles at the MYH9 locus and the disease. The strongest deviation from a null hypothesis of random sharing was obtained with two adjacent SNPs, rs3752462 and rs2009930 (global p value = 0.001), indicating that MYH9 might be a predisposing factor for CL/P, although its pathogenetic role needs to be investigated more accurately. PMID- 17337619 TI - Self-reported exercise behavior and interpretations of exercise in older adults. AB - Prior exercise experiences may influence interpretations of exercise, ultimately affecting exercise behavior. This study examines differences in interpretations of exercise in older adults based on prior exercise behavior. Older adults who report more exercise behavior were hypothesized to score more positively on measures of interpretations of exercise than older adults reporting less exercise behavior. Two hundred fifteen older adults reported prior-year exercise behavior, and within a 2-week exercise training program reported their episode-specific and general interpretations of exercise. High exercisers reported higher perceptions of energy (p = .021), life enhancement (p = .023), and overall psychological outlook (p = .003) than low exercisers. Several gender differences were also noted. These results support earlier findings that older adults' beliefs and interpretations of exercise activity influence exercise behavior. PMID- 17337620 TI - Functional trajectories associated with hospitalization in older adults. AB - For older adults, acute-care hospital stays can result in functional decline that leads to increased risk of hospitalization, nursing home admission, or mortality. This study describes functional trajectories in hospitalized older adults and identifies risk factors associated with those trajectories. Respondents (N = 45) exhibited five of six possible functional trajectory patterns. The largest change in functional status was a decline in activities of daily living (ADL) from baseline at 2 weeks before admission to the time of admission; ADL did not return to baseline during the first 4 days in the hospital. Depression scores were significantly higher in respondents who reported experiencing ADL decline before admission. Respondents whose ADL scores declined during hospitalization (regardless of baseline status) were more likely than others to die within 3 months of discharge. Functional trajectory in hospitalized elderly patients is an important and underappreciated prognostic concept requiring further attention. PMID- 17337621 TI - Women's well-being after relocation to independent living communities. AB - Late-life relocation to independent living communities is increasing, especially among women. This study described the impact of relocation on the health and well being of 31 older women who moved from a private residence to an independent living community. Schumacher and Meleis' (1994) nursing model of transition guided the study. Health status, social activity, self-esteem, depression, and quality of life were measured pre- and postmove. Post-move women reported a significant increase in engagement in social activities and higher quality of life. Participants' levels of self-esteem, depression, and quality of life were found to correspond with three relocation transition styles: full integration, partial integration, and minimal integration. These preliminary findings suggest that nurses who identify older women with low self-esteem, high depressive symptoms, and low quality of life pre-move may be at risk for poor relocation outcomes. Interventions to ease the transition process and improve relocation adjustment are needed. PMID- 17337622 TI - Extending work environment research into home health settings. AB - Organizational attributes in work environments that support nursing practice are theoretically associated with superior nurse and patient outcomes, and lower frequencies of adverse events. This study explored associations between organizational support for nursing practice in home health care agencies and (a) the frequency of nurse-reported adverse events, (b) nurse-assessed quality of care, (c) nurse job satisfaction, and (d) nurses' intentions to leave their employing agency. Data were collected from a sample of 137 registered nurses employed as home health staff nurses in the United States and analyzed using descriptive techniques and bivariate correlation. As anticipated, organizational support for nursing was negatively associated with nurse-reported adverse patient events and intent to leave, and positively associated with nurse-assessed quality of care and job satisfaction. These findings may be helpful to nursing administrators who seek to create work environments in home health agencies that maximize patient outcomes and nurse satisfaction. PMID- 17337623 TI - Effects of fathers' attendance to labor and delivery on the experience of childbirth in Turkey. AB - This study was planned to experimentally determine the effects of fathers' attendance to labor and delivery on the experience of childbirth. Fifty primigravidae low-risk women and their partners were recruited to the study. The first 25 women were included in the experimental group, and their partners were allowed to participate in birth. The remaining 25 women were included in the control group, and their partners were not allowed to participate in birth. Perception of Birth Scale and Father Interview Form were used to evaluate couples' experiences during labor and delivery. In conclusion, fathers' support in birth helped mothers to have more positive experiences in all aspects of childbirth. There was no relationship between fathers' support and length of labor, use of pain-relieving drugs, or obstetric interventions in birth. When mother and father were supported during labor and delivery, the rate of the fathers who adopted an active role was high. PMID- 17337624 TI - Video recruitment of non-English-speaking participants. AB - Recruitment of underserved participants begins to close the disparity gap evident within disadvantaged communities, and innovative approaches to recruitment support this effort. Literacy, communication, and credibility barriers distance potential research participants. The literature search from 1975 to 2005 included the Cochrane Review, MEDLINE, EBSCO, PsycINFO, Google Scholar, and CINAHL for the terms video recruitment, videotaped, minority recruitment, and research subject recruitment with no documented use of videotape recruitment of non-English speaking (NES) participants. Based on this review, an innovative recruitment video was developed and targeted to monolingual Hispanic mothers to explain a study using home safety visits. Community assistants collaborated on the script. In 4 minutes, potential participants, some illiterate, saw what they could not read, and also whom they should expect at their door if they decided to participate. A total of 82 women were recruited, and with a retention rate of 95%. Classic minority recruitment barriers are reducible with this approach. PMID- 17337625 TI - Phosphatase and tensin homolog deleted on chromosome 10 suppression is an important process in peroxisome proliferator-activated receptor-gamma signaling in adipocytes and myotubes. AB - Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation enhances insulin sensitivity in type 2 diabetes mellitus. However, downstream mediators of PPARgamma activation in adipocytes and myotubes, the most important cell types involved in glucose homeostasis, remained unclear. Here we show by using two synthetic PPARgamma agonists (rosiglitazone and KR-62776, a novel PPARgamma agonist) that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a key downstream mediator of PPARgamma signaling. The PPARgamma agonists down regulated PTEN expression, resulting in glucose uptake increase in differentiated 3T3-L1 adipocytes and C2C12 skeletal muscle cells. In both cells, PTEN knockdown increased glucose uptake, whereas overexpression abolished the agonist-induced effects. The effects of PPARgamma agonists on PTEN expression and glucose uptake disappeared by pretreatment with a PPARgamma antagonist or by knockdown of PPARgamma expression. In vivo treatment of the agonists to C57BL/6J-ob/ob mice resulted in the reduction of PTEN level in both adipose and skeletal muscle tissues and decreased plasma glucose levels. Thus, these results suggest that PTEN suppression is a key mechanism of the PPARgamma-mediated glucose uptake stimulation in insulin-sensitive cells such as adipocytes and skeletal muscle cells, thereby restoring glucose homeostasis in type 2 diabetes. PMID- 17337626 TI - The mismatch repair protein MLH1 marks a subset of strongly interfering crossovers in tomato. AB - In most eukaryotes, the prospective chromosomal positions of meiotic crossovers are marked during meiotic prophase by protein complexes called late recombination nodules (LNs). In tomato (Solanum lycopersicum), a cytological recombination map has been constructed based on LN positions. We demonstrate that the mismatch repair protein MLH1 occurs in LNs. We determined the positions of MLH1 foci along the 12 tomato chromosome pairs (bivalents) during meiotic prophase and compared the map of MLH1 focus positions with that of LN positions. On all 12 bivalents, the number of MLH1 foci was approximately 70% of the number of LNs. Bivalents with zero MLH1 foci were rare, which argues against random failure of detecting MLH1 in the LNs. We inferred that there are two types of LNs, MLH1-positive and MLH1-negative LNs, and that each bivalent gets an obligate MLH1-positive LN. The two LN types are differently distributed along the bivalents. Furthermore, cytological interference among MLH1 foci was much stronger than interference among LNs, implying that MLH1 marks the positions of a subset of strongly interfering crossovers. Based on the distances between MLH1 foci or LNs, we propose that MLH1-positive and MLH1-negative LNs stem from the same population of weakly interfering precursors. PMID- 17337627 TI - Single gene-mediated shift in pollinator attraction in Petunia. AB - Animal-mediated pollination is essential in plant reproductive biology and is often associated with pollination syndromes, sets of floral traits, such as color, scent, shape, or nectar content. Selection by pollinators is often considered a key factor in floral evolution and plant speciation. Our aim is the identification and characterization of the genetic changes that caused the evolution of divergent pollination syndromes in closely related plant species. We focus on ANTHOCYANIN2 (AN2), a well-defined myb-type transcription factor that is a major determinant of flower color variation between Petunia integrifolia and Petunia axillaris. Analysis of sequence variation in AN2 in wild P. axillaris accessions showed that loss-of-function alleles arose at least five times independently. DNA sequence analysis was complemented by functional assays for pollinator preference using genetic introgressions and transgenics. These results show that AN2 is a major determinant of pollinator attraction. Therefore, changes in a single gene cause a major shift in pollination biology and support the notion that the adaptation of a flowering plant to a new pollinator type may involve a limited number of genes of large effect. Gene identification and analysis of molecular evolution in combination with behavioral and ecological studies can ultimately unravel the evolutionary genetics of pollination syndromes. PMID- 17337628 TI - The N-terminal double-stranded RNA binding domains of Arabidopsis HYPONASTIC LEAVES1 are sufficient for pre-microRNA processing. AB - Arabidopsis thaliana HYPONASTIC LEAVES1 (HYL1) is a microRNA (miRNA) biogenesis protein that contains two N-terminal double-stranded RNA binding domains (dsRBDs), a putative nuclear localization site (NLS), and a putative protein protein interaction domain. The interaction of HYL1 with DICER-LIKE1 is important for the efficient and precise processing of miRNA primary transcripts in plant miRNA biogenesis. To define the roles of the various domains of HYL1 in miRNA processing and the miRNA-directed phenotype, we transferred a series of HYL1 deletion constructs into hyl1 null mutants. The N-terminal region containing dsRBD1 and dsRBD2 completely rescued the mutant phenotype of hyl1, triggering the accumulation of miR166 and miR160 and resulting in reduced mRNA levels of the targeted genes. In vivo biochemical analysis of the HYL1-containing complexes from the transgenic plants revealed that the N-terminal dsRBDs of HYL1 were sufficient for processing miRNA precursors and the generation of mature miRNA. Transient and stable expression analysis demonstrated that the putative NLS domain was indeed the nuclear localization signal, whereas the N-terminal region containing the dsRBDs was not restricted to the nucleus. We suggest that the N terminal dsRBDs fulfill the function of the whole HYL1 and thus play an essential role in miRNA processing and miRNA-directed silencing of targeted genes. PMID- 17337629 TI - Arabidopsis MICROTUBULE-ASSOCIATED PROTEIN18 functions in directional cell growth by destabilizing cortical microtubules. AB - Microtubule-associated proteins (MAPs) play important roles in the regulation of microtubule function in cells. We describe Arabidopsis thaliana MAP18, which binds to microtubules and inhibits tubulin polymerization in vitro and colocalizes along cortical microtubules as patches of dot-like structures. MAP18 is expressed mostly in the expanding cells. Cells overexpressing MAP18 in Arabidopsis exhibit various growth phenotypes with loss of polarity. Cortical microtubule arrays were significantly altered in cells either overexpressing MAP18 or where it had been downregulated by RNA interference (RNAi). The cortical microtubules were more sensitive to treatment with microtubule-disrupting drugs when MAP18 was overexpressed, but more resistant when MAP18 was eliminated in cells expressing MAP18 RNAi. Our study demonstrated that MAP18 may play a role in regulating directional cell growth and cortical microtubule organization by destabilizing microtubules. PMID- 17337630 TI - Analysis of transcription factor HY5 genomic binding sites revealed its hierarchical role in light regulation of development. AB - The transcription factor LONG HYPOCOTYL5 (HY5) acts downstream of multiple families of the photoreceptors and promotes photomorphogenesis. Although it is well accepted that HY5 acts to regulate target gene expression, in vivo binding of HY5 to any of its target gene promoters has yet to be demonstrated. Here, we used a chromatin immunoprecipitation procedure to verify suspected in vivo HY5 binding sites. We demonstrated that in vivo association of HY5 with promoter targets is not altered under distinct light qualities or during light-to-dark transition. Coupled with DNA chip hybridization using a high-density 60 nucleotide oligomer microarray that contains one probe for every 500 nucleotides over the entire Arabidopsis thaliana genome, we mapped genome-wide in vivo HY5 binding sites. This analysis showed that HY5 binds preferentially to promoter regions in vivo and revealed >3000 chromosomal sites as putative HY5 binding targets. HY5 binding targets tend to be enriched in the early light-responsive genes and transcription factor genes. Our data thus support a model in which HY5 is a high hierarchical regulator of the transcriptional cascades for photomorphogenesis. PMID- 17337631 TI - PIC1, an ancient permease in Arabidopsis chloroplasts, mediates iron transport. AB - In chloroplasts, the transition metals iron and copper play an essential role in photosynthetic electron transport and act as cofactors for superoxide dismutases. Iron is essential for chlorophyll biosynthesis, and ferritin clusters in plastids store iron during germination, development, and iron stress. Thus, plastidic homeostasis of transition metals, in particular of iron, is crucial for chloroplast as well as plant development. However, very little is known about iron uptake by chloroplasts. Arabidopsis thaliana PERMEASE IN CHLOROPLASTS1 (PIC1), identified in a screen for metal transporters in plastids, contains four predicted alpha-helices, is targeted to the inner envelope, and displays homology with cyanobacterial permease-like proteins. Knockout mutants of PIC1 grew only heterotrophically and were characterized by a chlorotic and dwarfish phenotype reminiscent of iron-deficient plants. Ultrastructural analysis of plastids revealed severely impaired chloroplast development and a striking increase in ferritin clusters. Besides upregulation of ferritin, pic1 mutants showed differential regulation of genes and proteins related to iron stress or transport, photosynthesis, and Fe-S cluster biogenesis. Furthermore, PIC1 and its cyanobacterial homolog mediated iron accumulation in an iron uptake-defective yeast mutant. These observations suggest that PIC1 functions in iron transport across the inner envelope of chloroplasts and hence in cellular metal homeostasis. PMID- 17337632 TI - Alpha1A-adrenergic receptors are functionally expressed by a subpopulation of cornu ammonis 1 interneurons in rat hippocampus. AB - The importance of adrenergic receptors (ARs) in the hippocampus has generally focused on betaARs; however, interest is growing in hippocampal alphaARs given their purported neuroprotective role. We have previously reported alpha(1)AR transcripts in a subpopulation of cornu ammonis 1 (CA1) interneurons. The goal of this study was to identify the specific alpha(1)AR subtype (alpha(1A), alpha(1B), alpha(1D)) functionally expressed by these cells. Using cell-attached recordings to measure action potential frequency changes, concentration-response curves for the selective alpha(1)AR agonist phenylephrine (PE) were generated in the presence of competitive subtype-selective alpha(1)AR antagonists. Schild regression analysis was then used to estimate equilibrium dissociation constants (K(b)) for each receptor antagonist in our system. The selective alpha(1A)AR antagonists, 5-methylurapidil and WB-4101 [2-[(2,6 dimethoxyphenoxyethyl)aminomethyl]-1,4-benzodioxane hydrochloride], produced consecutive rightward shifts in the concentration-response curve for PE when used at discriminating, nanomolar concentrations. Calculated K(b) values for 5 methylurapidil (10 nM) and WB-4101 (5 nM) correlate to previously published affinity values for these antagonists at the alpha(1A)AR. The selective alpha(1B)AR antagonist L-765,314 [(2S)-4-(4-amino-6,7-dimethoxy-2-quinazolinyl)-2 [[(1,1-dimethylethyl)amino]carbonyl]-1-piperazinecarboxylic acid], as well as the selective alpha(1D)AR antagonist BMY7378 [8-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride], produced significant rightward shifts in the concentration-response curve for PE only when used at nondistinguishing, micromolar concentrations. Calculated K(b) values for L-765,314 (794 nM) and BMY7378 (316 nM) do not agree with affinity values for these antagonists at the alpha(1B) or alpha(1D)AR, respectively. Rather, these K(b) values more closely match equilibrium dissociation constants estimated for these compounds when used to identify alpha(1A)AR subtypes. Together, our results provide strong evidence to support functional expression of alpha(1A)ARs in a subpopulation of CA1 interneurons. PMID- 17337633 TI - Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors. AB - 2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines are 5 hydroxytryptamine (serotonin) (5-HT)(2A/2C) agonists. The former are partial to full agonists, whereas the latter are partial to weak agonists. However, most data come from studies analyzing phospholipase C (PLC)-mediated responses, although additional effectors [e.g., phospholipase A(2) (PLA(2))] are associated with these receptors. We compared two homologous series of phenylisopropylamines and phenethylamines measuring both PLA(2) and PLC responses in Chinese hamster ovary-K1 cells expressing human 5-HT(2A) or 5-HT(2C) receptors. In addition, we assayed both groups of compounds as head shake inducers in rats. At the 5-HT(2C) receptor, most compounds were partial agonists for both pathways. Relative efficacy of some phenylisopropylamines was higher for both responses compared with their phenethylamine counterparts, whereas for others, no differences were found. At the 5-HT(2A) receptor, most compounds behaved as partial agonists, but unlike findings at 5-HT(2C) receptors, all phenylisopropylamines were more efficacious than their phenethylamine counterparts. 2,5 Dimethoxyphenylisopropylamine activated only the PLC pathway at both receptor subtypes, 2,5-dimethoxyphenethylamine was selective for PLC at the 5-HT(2C) receptor, and 2,5-dimethoxy-4-nitrophenethylamine was PLA(2)-specific at the 5 HT(2A) receptor. For both receptors, the rank order of efficacy of compounds differed depending upon which response was measured. The phenylisopropylamines were strong head shake inducers, whereas their phenethylamine congeners were not, in agreement with in vitro results and the involvement of 5-HT(2A) receptors in the head shake response. Our results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile. PMID- 17337634 TI - The MAD1 adhesin of Metarhizium anisopliae links adhesion with blastospore production and virulence to insects, and the MAD2 adhesin enables attachment to plants. AB - Metarhizium anisopliae is a fungus of considerable metabolic and ecological versatility, being a potent insect pathogen that can also colonize plant roots. The mechanistic details of these interactions are unresolved. We provide evidence that M. anisopliae adheres to insects and plants using two different proteins, MAD1 and MAD2, that are differentially induced in insect hemolymph and plant root exudates, respectively, and produce regional localization of adhesive conidial surfaces. Expression of Mad1 in Saccharomyces cerevisiae allowed this yeast to adhere to insect cuticle. Expression of Mad2 caused yeast cells to adhere to a plant surface. Our study demonstrated that as well as allowing adhesion to insects, MAD1 at the surface of M. anisopliae conidia or blastospores is required to orientate the cytoskeleton and stimulate the expression of genes involved in the cell cycle. Consequently, the disruption of Mad1 in M. anisopliae delayed germination, suppressed blastospore formation, and greatly reduced virulence to caterpillars. The disruption of Mad2 blocked the adhesion of M. anisopliae to plant epidermis but had no effects on fungal differentiation and entomopathogenicity. Thus, regulation, localization, and specificity control the functional distinction between Mad1 and Mad2 and enable M. anisopliae cells to adapt their adhesive properties to different habitats. PMID- 17337636 TI - Evolution of the mating type locus: insights gained from the dimorphic primary fungal pathogens Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii. AB - Sexual reproduction of fungi is governed by the mating type (MAT) locus, a specialized region of the genome encoding key transcriptional regulators that direct regulatory networks to specify cell identity and fate. Knowledge of MAT locus structure and evolution has been considerably advanced in recent years as a result of genomic analyses that enable the definition of MAT locus sequences in many species as well as provide an understanding of the evolutionary plasticity of this unique region of the genome. Here, we extend this analysis to define the mating type locus of three dimorphic primary human fungal pathogens, Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii, using genomic analysis, direct sequencing, and bioinformatics. These studies provide evidence that all three species possess heterothallic bipolar mating type systems, with isolates encoding either a high-mobility-group (HMG) domain or an alpha-box transcriptional regulator. These genes are intact in all loci examined and have not been subject to loss or decay, providing evidence that the loss of fertility upon passage in H. capsulatum is not attributable to mutations at the MAT locus. These findings also suggest that an extant sexual cycle remains to be defined in both Coccidioides species, in accord with population genetic evidence. Based on these MAT sequences, a facile PCR test was developed that allows the mating type to be rapidly ascertained. Finally, these studies highlight the evolutionary forces shaping the MAT locus, revealing examples in which flanking genes have been inverted or subsumed and incorporated into an expanding MAT locus, allowing us to propose an expanded model for the evolution of the MAT locus in the phylum Ascomycota. PMID- 17337637 TI - Mg2+ deprivation elicits rapid Ca2+ uptake and activates Ca2+/calcineurin signaling in Saccharomyces cerevisiae. AB - To learn about the cellular processes involved in Mg(2+) homeostasis and the mechanisms allowing cells to cope with low Mg(2+) availability, we performed RNA expression-profiling experiments and followed changes in gene activity upon Mg(2+) depletion on a genome-wide scale. A striking portion of genes up-regulated under Mg(2+) depletion are also induced by high Ca(2+) and/or alkalinization. Among the genes significantly up-regulated by Mg(2+) starvation, Ca(2+) stress, and alkalinization are ENA1 (encoding a P-type ATPase sodium pump) and PHO89 (encoding a sodium/phosphate cotransporter). We show that up-regulation of these genes is dependent on the calcineurin/Crz1p (calcineurin-responsive zinc finger protein) signaling pathway. Similarly to Ca(2+) stress, Mg(2+) starvation induces translocation of the transcription factor Crz1p from the cytoplasm into the nucleus. The up-regulation of ENA1 and PHO89 upon Mg(2+) starvation depends on extracellular Ca(2+). Using fluorescence resonance energy transfer microscopy, we demonstrate that removal of Mg(2+) results in an immediate increase in free cytoplasmic Ca(2+). This effect is dependent on external Ca(2+). The results presented indicate that Mg(2+) depletion in yeast cells leads to enhanced cellular Ca(2+) concentrations, which activate the Crz1p/calcineurin pathway. We provide evidence that calcineurin/Crz1p signaling is crucial for yeast cells to cope with Mg(2+) depletion stress. PMID- 17337638 TI - Parallel beta-helix proteins required for accurate capsule polysaccharide synthesis and virulence in the yeast Cryptococcus neoformans. AB - The principal capsular polysaccharide of the opportunistic fungal pathogen Cryptococcus neoformans consists of an alpha-1,3-linked mannose backbone decorated with a repeating pattern of glucuronyl and xylosyl side groups. This structure is critical for virulence, yet little is known about how the polymer, called glucuronoxylomannan (GXM), is faithfully synthesized and assembled. We have generated deletions in two genes encoding predicted parallel beta-helix repeat proteins, which we have designated PBX1 and PBX2. Deletion of either gene results in a dry-colony morphology, clumpy cells, and decreased capsule integrity. Two-dimensional nuclear magnetic resonance spectroscopy of purified GXM from the mutants indicated that both the wild-type GXM structure and novel, aberrant linkages were present. Carbohydrate composition and linkage analysis determined that these aberrant structures are correlated with the incorporation of terminal glucose residues that are not found in wild-type capsule polysaccharide. We conclude that Pbx1 and Pbx2 are required for the fidelity of GXM synthesis and may be involved in editing incorrectly added glucose residues. PBX1 and PBX2 knockout mutants showed severely attenuated virulence in a murine inhalation model of cryptococcosis. Unlike acapsular strains, these mutant strains induced delayed symptoms of cryptococcosis, though the infected animals eventually contained the infection and recovered. PMID- 17337635 TI - Mechanisms regulating the protein kinases of Saccharomyces cerevisiae. PMID- 17337639 TI - Expression and interstrain variability of the YPS3 gene of Histoplasma capsulatum. AB - The YPS3 locus of the dimorphic fungus Histoplasma capsulatum encodes a secreted and surface-localized protein specific to the pathogenic yeast phase. In this study we examined this locus in 32 H. capsulatum strains and variants. Although protein production is limited to a select group of strains, the North American restriction fragment length polymorphism class 2/NAm 2 isolates, the locus was present in all the strains we examined. The YPS3 gene is well conserved in its 5' and 3' regions but displays an intragenic hypervariable region of tandem repeats that fluctuates in size between strains. This feature is similar to that seen with genes encoding several cell surface proteins in other fungi. PMID- 17337640 TI - Exposure to solvents and risk of non-Hodgkin lymphoma: clues on putative mechanisms. AB - Malignant lymphomas are a group of diseases of uncertain etiology. Both environmental factors and genetic susceptibility have been reported as risk factors. We have conducted a population-based case-control study in Italy: all newly diagnosed cases of malignant lymphoma, in males and females ages 20 to 74 years in the 1991 to 1993 period, were identified; the control group was comprised of a random sample of the general population resident in each of the areas under study, stratified by sex and 5-year age groups. Overall, 1,428 non Hodgkin lymphoma (NHL) cases and 1,530 controls were interviewed. Experts from each geographic area examined questionnaire data and assigned a level of probability and intensity of exposure to a range of chemical groups and individual chemicals. For those in the medium/high level of exposure, there was an increased risk of NHL for exposure to benzene, xylene, and toluene. We have examined the hypothesis that the effect of solvents is related to their immunotoxicity by analyzing the interaction with a previous history of autoimmune disease. We have found an apparent, though not statistically significant, increased risk of NHL in those with both exposure to benzene and a history of autoimmune disease (odds ratio, 16.3; 95% confidence interval, 0.8-321). In addition, an odds ratio of 29.8 (95% confidence interval, 1.4-650.2, based on nine exposed cases) was associated with high-level exposure to benzene in those with a positive family history of malignant hematologic neoplasms. Both hypotheses (i.e., the interaction with autoimmune diseases and with familial predisposition) indirectly suggest that an immunologic mechanism could be involved in lymphomagenesis from solvents. PMID- 17337641 TI - Polychlorinated biphenyls and non-Hodgkin lymphoma. AB - Several epidemiologic studies suggest that polychlorinated biphenyl (PCB) levels measured in peripheral blood or adipose tissue are related to increased risk of non-Hodgkin lymphoma (NHL) and, therefore, may be at least partially responsible for the rising incidence of NHL unrelated to HIV infection in recent decades. Case-control studies that measured PCBs in blood, adipose tissue, or household carpet dust, at the time of diagnosis, have observed elevated NHL risk associated with concentrations of either total PCBs or of specific congeners. Similar associations have been found in a number of prospective cohorts. These associations do not seem to be due to confounding by other organochlorines or by other known NHL risk factors. These results support evidence of PCB carcinogenicity from animal studies. However, interpretation of the epidemiologic evidence is limited by the wide range in measurement precision across congeners and by the moderate to high correlation among many congeners. Occupational cohort studies provide very limited support for a relationship between PCBs and NHL. In conclusion, there is mounting evidence of a relationship between certain PCBs and risk of NHL, but important questions remain, especially regarding the magnitude, timing, and causality of that relationship. PMID- 17337642 TI - Obesity, diet and risk of non-Hodgkin lymphoma. AB - Non-Hodgkin lymphoma (NHL) represents a group of heterogeneous diseases that significantly vary in their causes, molecular profiles, and natural progression. In 2007, there will be approximately 59,000 newly diagnosed NHL cases in the United States and over 300,000 cases worldwide. Although new therapeutic regimens are minimizing the number of deaths related to NHL, causes for the majority of lymphomas remain undetermined. Recent studies suggest that dietary factors may contribute to the rising rates of NHL. This review will summarize epidemiologic reports that have studied the relationship between obesity, physical activity, and diet and risk of NHL. Based on a number of case-control and prospective cohort studies, overweight/obesity probably increases the risk of NHL, whereas moderate physical activity may reduce risk. Several studies support an inverse association between intakes of vegetables and NHL risk, particularly for the consumption of cruciferous vegetables. This may relate to the induction of apoptosis and growth arrest in preneoplastic and neoplastic cells, two important actions of isothiocyanates found in cruciferous vegetables. Studies also suggest that fish intake may be inversely associated with risk of NHL, although findings have not been entirely consistent. This may relate to the high organochlorine content in some fish that could override a protective effect. High consumption of fats, meat, and dairy products also may increase lymphoma risk. The accumulated scientific evidence concerning the associations between obesity, diet, and NHL suggests several identified modifiable risk factors that might be recommended to decrease lymphoma risk. PMID- 17337643 TI - Altered immunity as a risk factor for non-Hodgkin lymphoma. AB - This review examines the association between disorders of immunity, including immune deficiency, atopy, and autoimmune disease, and non-Hodgkin lymphoma (NHL). Immune deficiency is one of the strongest known risk factors for NHL. Risk is increased whether the immune deficiency is congenital, iatrogenic, or acquired. Risk of NHL increases with degree of immune deficiency, and there is no evidence of a threshold. In the profoundly immune deficient, NHL is frequently caused by infection with the ubiquitous EBV. Whether mild, subclinical immune deficiency is related to increased NHL risk is unknown. There is inconsistent evidence that atopic conditions, such as asthma, hayfever, and eczema, characterized by an immune response that is skewed toward Th2, are associated with a decreased risk of NHL. These data come mainly from case-control studies. Concern has been expressed that the association may be due to reverse causality if early symptoms of NHL include a lessening of atopic manifestations. Case-control and cohort studies of people with autoimmune conditions have generally shown that rheumatoid arthritis, systemic lupus erythematosis, and Sjogren's disease are associated with increased NHL risk. It seems to be the intensity of the inflammatory disease rather than its treatment which is related to increased risk of NHL. The study of altered immunity as a cause of NHL in case-control studies is limited by the fact that development of NHL in itself leads to altered immunity. Cohort studies of the role of altered immunity should be a top priority in epidemiologic studies of NHL etiology. PMID- 17337644 TI - Sun exposure and non-Hodgkin lymphoma. AB - It was initially hypothesized that sun exposure might cause non-Hodgkin lymphoma (NHL) on the following grounds: its incidence was increasing in parallel with that of cutaneous melanoma; its risk was increased in those with a history of melanoma or other skin cancer; sun exposure causes immune suppression; and immunosuppression for other reasons is associated with an increased risk of NHL. The association of NHL with prior skin cancer has been found consistently in subsequent studies, but results of ecological analyses have only partially supported this hypothesis. Contrary to it, three recent studies of NHL in individuals found that risk decreased, generally by 25% to 40%, across categories of increasing total or recreational, but not occupational, sun exposure. One study, thus far reported only in abstract, showed the opposite. Production of vitamin D from sun exposure offers a plausible mechanism for protection against NHL by sun exposure. A recent study has found a reduced risk of NHL in people with a high dietary intake of vitamin D. Results of additional studies in individuals and a planned original-data meta-analysis of case-control studies should help to resolve the present conflicting results on sun exposure and NHL. PMID- 17337645 TI - Benzene exposure and risk of non-Hodgkin lymphoma. AB - Exposure to benzene, an important industrial chemical and component of gasoline, is a widely recognized cause of leukemia, but its association with non-Hodgkin lymphoma (NHL) is less clear. To clarify this issue, we undertook a systematic review of all case-control and cohort studies that identified probable occupational exposures to benzene and NHL morbidity or mortality. We identified 43 case-control studies of NHL outcomes that recognized persons with probable occupational exposure to benzene. Forty of these 43 (93%) studies show some elevation of NHL risk, with 23 of 43 (53%) studies finding statistically significant associations between NHL risk and probable benzene exposure. We also identified 26 studies of petroleum refinery workers reporting morbidity or mortality for lymphomas and all neoplasms and found that in 23 (88%), the rate of lymphoma morbidity or mortality was higher than that for all neoplasms. A substantial healthy-worker effect was evident in many of the studies and a comprehensive reevaluation of these studies with appropriate adjustments should be undertaken. Numerous studies have also reported associations between benzene exposure and the induction of lymphomas in mice. Further, because benzene is similar to alkylating drugs and radiation in producing leukemia, it is plausible that it might also produce lymphoma as they do and by similar mechanisms. Potential mechanisms include immunotoxicity and the induction of double-strand breaks with subsequent chromosome damage resulting in translocations and deletions. We conclude that, overall, the evidence supports an association between occupational benzene exposure and NHL. PMID- 17337646 TI - Infectious agents as causes of non-Hodgkin lymphoma. AB - Among exposures presently viewed as possible etiologic factors in non-Hodgkin lymphoma (NHL), infections are close to being regarded as established causes. Infectious agents causing NHL can be classified, according to mechanism, into three broad groups. First, some viruses can directly transform lymphocytes. Lymphocyte-transforming viruses include Epstein Barr virus (linked to Burkitt's lymphoma, NHLs in immunosuppressed individuals, and extranodal natural killer/T cell NHL), human herpesvirus 8 (primary effusion lymphoma), and human T lymphotropic virus type I (adult T-cell leukemia/lymphoma). Second, human immunodeficiency virus is unique in causing profound depletion of CD4+ T lymphocytes, leading to acquired immunodeficiency syndrome and an associated high risk for some NHL subtypes. Third, recent evidence suggests that some infections increase NHL risk through chronic immune stimulation. These infections include hepatitis C virus as well as certain bacteria that cause chronic site-specific inflammation and seem to increase risk for localized mucosa-associated lymphoid tissue NHLs. Establishing that an infectious agent causes NHL depends on showing that the agent is present in persons with NHL as well as laboratory experiments elucidating the mechanisms involved. Only epidemiologic studies can provide evidence that infection is actually a risk factor by showing that infection is more frequent in NHL cases than in controls. Given the range of mechanisms by which infections could plausibly cause NHL and our growing molecular understanding of this malignancy, this field of research deserves continued attention. PMID- 17337647 TI - Predictors of participation in a smoking cessation program among young adult smokers. AB - This study investigated the predictors of participation in a smoking cessation trial for young adults ages 18 to 30 years old. Eligible smokers (n = 164) completed a telephone survey that measured demographic, smoking history, and psychosocial variables before the initiation of smoking cessation treatment. Young adult smokers who attended at least one smoking cessation session were compared with those who did not attend any sessions. Logistic regression analysis indicated that race and age were statistically significant multivariate predictors of participation. Caucasians were over six times (odds ratio, 6.03; 95% confidence interval, 2.41-15.05) more likely to participate in the smoking cessation program compared with non-Caucasians (61% versus 19%). For every SD increase in age (SD, 2.45), there was about a 2-fold increase in the likelihood that a young adult smoker participated in the smoking cessation program (odds ratio, 1.82; 95% confidence interval, 1.23-2.71). Future research should investigate how to promote participation in smoking cessation programs among smokers in emerging adulthood and among non-Caucasian young adult smokers to prevent a lifelong habit associated with disproportionate morbidity and mortality. PMID- 17337648 TI - Soy product and isoflavone consumption in relation to prostate cancer in Japanese men. AB - The incidence of prostate cancer is much lower in Asian than Western populations. Environmental factors, such as dietary habits, may play a major role in the causation of prostate cancer. Although isoflavones have been suggested to show a preventive effect against prostate cancer in animal experiments, the results of epidemiologic studies are inconsistent. Here, we conducted a population-based prospective study in 43,509 Japanese men ages 45 to 74 years who generally have a high intake of isoflavones and low incidence of prostate cancer. Participants responded to a validated questionnaire, which included 147 food items. During follow-up from 1995 through 2004, 307 men were newly diagnosed with prostate cancer, of which 74 cases were advanced, 220 cases were organ localized, and 13 cases were of an undetermined stage. Intakes of genistein, daidzein, miso soup, and soy food were not associated with total prostate cancer. However, these four items decreased the risk of localized prostate cancer. In contrast, positive associations were seen between isoflavones and advanced prostate cancer. These results were strengthened when analysis was confined to men ages >60 years, in whom isoflavones and soy food were associated with a dose-dependent decrease in the risk of localized cancer, with relative risks for men in the highest quartile of genistein, daidzein, and soy food consumption compared with the lowest of 0.52 [95% confidence interval (95% CI), 0.30-0.90], 0.50 (95% CI, 0.28-0.88), and 0.52 (95% CI, 0.29-0.90), respectively. In conclusion, we found that isoflavone intake was associated with a decreased risk of localized prostate cancer. PMID- 17337649 TI - Potential for colorectal cancer prevention of sigmoidoscopy versus colonoscopy: population-based case control study. AB - We aimed to estimate the proportions of colorectal cancer cases that might be prevented by sigmoidoscopy compared with colonoscopy among women and men. In a population-based case control study conducted in Germany, 540 cases with a first diagnosis of primary colorectal cancer and 614 controls matched for age, sex, and county of residence were recruited. A detailed lifetime history of endoscopic examinations of the large bowel was obtained by standardized personal interviews, validated by medical records, and compared between cases and controls, paying particular attention to location of colorectal cancer and sex differences. Overall, 39%, 77%, and 64% of proximal, distal, and total colorectal cancer cases were estimated to be preventable by colonoscopy. The estimated proportion of total colorectal cancer cases preventable by sigmoidoscopy was 45% among both women and men, assuming that sigmoidoscopy reaches the junction of the descending and sigmoid colon only and findings of distal polyps are not followed by colonoscopy. Assuming that sigmoidoscopy reaches the splenic flexure and colonoscopy is done after detection of distal polyps, estimated proportions of total colorectal cancer preventable by sigmoidoscopy increase to 50% and 55% (73% and 91% of total colorectal cancer preventable by primary colonoscopy) among women and men, respectively. We conclude that colonoscopy provides strong protection against colorectal cancer among both women and men. The proportion of this protection achieved by sigmoidoscopy with follow-up colonoscopy in case of distal polyps may be larger than anticipated. Among men, this regimen may be almost as effective as colonoscopy, at least at previous performance levels of colonoscopy. PMID- 17337650 TI - Benign breast biopsy diagnosis and subsequent risk of breast cancer. AB - BACKGROUND: We examine benign breast biopsy diagnoses as reported by community pathologists in New Mexico and investigate associations with future breast cancer development. METHODS: Using data collected between 1992 and 2000 by the New Mexico Mammography Project and cancer data through 2003 from the New Mexico Tumor Registry, we calculated breast cancer rates following 14,602 benign breast biopsies for women ages 30 to 89 years. For comparison, we also calculated the breast cancer rate following 215,283 normal screening mammograms. Hazard ratios (HR) are presented. RESULTS: We identified 480 subsequent breast cancer diagnoses among 14,602 women with benign breast biopsies and 4,402 breast cancer diagnoses among 215,283 women with mammograms assigned a "negative" or "benign finding" assessment. Histologic diagnoses in absence of atypia had an age-adjusted HR of 1.95 [95% confidence interval (95% CI), 1.77-2.15]. Among low-risk histologic diagnoses, the strongest associations with subsequent breast cancer development included adenosis, apocrine metaplasia, calcifications, and ductal hyperplasia. Fibroadenoma, inflammation, and cysts did not exhibit an association with breast cancer development. Women with low-risk diagnoses and breast tissue characterized as fatty or with scattered densities had a HR of 2.09 (95% CI, 1.68-2.60), whereas women with low-risk histologic diagnoses and dense breasts had a HR of 3.36 (95% CI, 2.83-3.99). CONCLUSIONS: The observed breast cancer occurrence contributes to evidence of increased risk following benign biopsy. The risk associated with histologic diagnoses in absence of atypia was twice the risk experienced by women with normal mammogram evaluations and may be modified by breast density. PMID- 17337651 TI - Myocardial perfusion imaging protocols: is there an ideal protocol? AB - Is there an ideal myocardial perfusion imaging protocol? In order to answer this question and choose a protocol for clinical use, one must understand the characteristics of the available radiopharmaceuticals, the protocol variables, and the advantages and disadvantages of each. After reading this article, the technologist should be able to list the ideal characteristics of a myocardial perfusion imaging agent, describe and compare the characteristics of myocardial perfusion imaging agents, discuss the relationship between coronary blood flow and myocardial uptake of various tracers, describe imaging protocols, and discuss the advantages and disadvantages of each protocol. PMID- 17337652 TI - Evaluation and localization of lymphatic drainage and sentinel lymph nodes in patients with head and neck melanomas by hybrid SPECT/CT lymphoscintigraphic imaging. AB - In patients with head and neck tumors, preoperative lymphoscintigraphy can be used to map lymphatic drainage patterns and identify sentinel lymph nodes. However, it is very difficult to determine the exact locations of head and neck sentinel nodes on preoperative lymphoscintigraphy without the use of anatomic landmarks. Lymph nodes in the head and neck are grouped into 7 regions, or levels, on the basis of anatomic landmarks. In patients undergoing standard lymphoscintigraphy, obtaining lateral marker images that show important anatomic landmarks can help with the localization of sentinel nodes. However, technical problems often render marker images of little or no use. Hybrid SPECT/CT lymphoscintigraphic imaging facilitates the localization of sentinel nodes by reliably showing the relationships between sentinel nodes and important anatomic structures. After reading this article, the reader should understand the lymph node level classification system for head and neck melanomas, be able to describe the technique used for the imaging of sentinel nodes in the head and neck region, and be able to demonstrate how SPECT/CT lymphoscintigraphic imaging can enable precise sentinel node localization and thus help to ensure minimal dissection. PMID- 17337653 TI - Reproducibility of a standardized quantitative analysis using fixed regions of interest to differentiate movement disorders on 123I-FP-CIT SPECT. AB - The present prospective study evaluated the diagnostic value of a standardized analysis of (123)I-N-omega-(fluoropropyl)-2beta-carbomethoxy-3beta-(4 iodophenyl)tropane (FP-CIT) SPECT studies acquired on a triple-head gamma-camera for patients with clinically uncertain movement disorders having tremor as the most striking feature. METHODS: (123)I-FP-CIT studies were performed on 52 consecutive patients (27 male and 25 female; mean age, 49.2 y; range, 17-80 y) who had a clinical diagnosis of Parkinson's disease (PD) (n = 21), hypokinetic rigid syndrome (n = 19), dystonia (n = 8), or essential tremor (n = 4). In all patients, the final diagnosis was based on a thorough clinical examination, the family history, and a 2-y follow-up. Two independent technologists analyzed (123)I-FP-CIT studies using a standardized quantitative method applying both fixed regions of interest (ROIs) and manually drawn ROIs. The mean values from both methods were compared using the Student t test, and the intra- and intertechnologist variabilities were tested. RESULTS: In patients with PD, all ratios were significantly lower (P < 0.001) than those in patients with other movement disorders. No significant differences were found between the other groups tested. The manual method resulted in significantly lower values than did the standardized method (P < 0.001) and, for the putamen, showed significant differences between technologists. The standardized method showed no significant differences between technologists. The intra- and intertechnologist variabilities for this method were 0.14 +/- 0.13 (confidence value, 2.4%) and 0.19 +/- 0.18 (confidence value, 3.1%), respectively, whereas the intraclass correlation coefficients were 0.99 for 1 technologist and 0.98 for the 2 independent technologists. CONCLUSION: Our data confirm that (123)I-FP-CIT SPECT has value in the differentiation of PD from other movement disorders. Acquisition using a triple-head gamma-camera and subsequent standardized analysis using fixed ROIs result in good intra- and intertechnologist agreement and can easily be applied in clinical practice. PMID- 17337654 TI - Development and prospective evaluation of an automated software system for quality control of quantitative 99mTc-MAG3 renal studies. AB - Quantitative nuclear renography has numerous potential sources of error. We previously reported the initial development of a computer software module for comprehensively addressing the issue of quality control (QC) in the analysis of radionuclide renal images. The objective of this study was to prospectively test the QC software. METHODS: The QC software works in conjunction with standard quantitative renal image analysis using a renal quantification program. The software saves a text file that summarizes QC findings as possible errors in user entered values, calculated values that may be unreliable because of the patient's clinical condition, and problems relating to acquisition or processing. To test the QC software, a technologist not involved in software development processed 83 consecutive nontransplant clinical studies. The QC findings of the software were then tabulated. QC events were defined as technical (study descriptors that were out of range or were entered and then changed, unusually sized or positioned regions of interest, or missing frames in the dynamic image set) or clinical (calculated functional values judged to be erroneous or unreliable). RESULTS: Technical QC events were identified in 36 (43%) of 83 studies. Clinical QC events were identified in 37 (45%) of 83 studies. Specific QC events included starting the camera after the bolus had reached the kidney, dose infiltration, oversubtraction of background activity, and missing frames in the dynamic image set. CONCLUSION: QC software has been developed to automatically verify user input, monitor calculation of renal functional parameters, summarize QC findings, and flag potentially unreliable values for the nuclear medicine physician. Incorporation of automated QC features into commercial or local renal software can reduce errors and improve technologist performance and should improve the efficiency and accuracy of image interpretation. PMID- 17337655 TI - Simultaneous 3-dimensional resolution correction in SPECT reconstruction with an ordered-subsets expectation maximization algorithm. AB - Collimators are used for the improvement of information about the positions of sources by limiting the incidence direction of gamma-rays and characteristic x rays to detectors. In this study, we attempted to improve the spatial resolution of (201)Tl myocardial SPECT by using simultaneous 3-dimensional distance dependent resolution correction (DRC) incorporated into the ordered-subsets expectation maximization algorithm. METHODS: Simulation was performed with various sizes of balls, and measurement with a line-source phantom was performed at different source-detector distances. Imaging of a hot-rod phantom, the defect area of a myocardial phantom, and the myocardial thickness and cardiac lumen in a human study by (201)TlCl myocardial SPECT was evaluated before and after DRC. RESULTS: We performed simulation by using 5 sizes of balls and found marked improvement in resolution in all x-, y-, and z-axis directions. In the line source phantom, when the radial distance was very long (30.5 cm), the correction effects were slightly low. However, when the distance was similar to the clinically used rotation radius (22.5 cm), the correction effects were good in the hot-rod and myocardial phantoms and in the human study. CONCLUSION: DRC markedly improved the spatial resolution of SPECT images, suggesting that this method is useful for the quantification of infarcted areas by myocardial SPECT. PMID- 17337656 TI - Nuclear medicine practitioner competencies. PMID- 17337657 TI - Insights about nuclear medicine technology: findings from a 2006 survey of NMT education program directors. PMID- 17337658 TI - Candida parapsilosis infection in very low birthweight infants. AB - In a UK national surveillance study, we found that Candida parapsilosis accounted for one quarter of all cases of invasive fungal infection in very low birthweight infants. C parapsilosis was associated with fewer deep-seated infections than C albicans, but mortality was similar. Ongoing surveillance is needed to monitor the epidemiology of invasive fungal infection in very low birthweight infants. PMID- 17337659 TI - Effect of suckling on the peripheral sensitivity of full-term newborn infants. AB - BACKGROUND: Sucking may reduce the manifestations of pain in newborn infants. OBJECTIVE: To examine the effect of suckling on the threshold for peripheral somatosensory responses. SUBJECTS AND METHODS: Graded Von Frey filaments were applied to the heel to initiate peripheral somatosensory responses (withdrawal reflex and gross body movements) in term infants. RESULTS: Dummy sucking increases the somatosensory threshold, but breast feeding had a more marked effect, increasing the threshold of the flexion withdrawal reflex (p20 degrees C, neurally evoked relaxations of resting muscle tension are effective only at colder temperatures at which the inhibitory junction potentials are hyperpolarizing in polarity. 5-HT has two effects on inhibitory synaptic signals: it potentiates their amplitude and also shifts the temperature at which they reverse polarity by approximately +7 degrees C. Thus 5-HT both potentiates neurally evoked relaxations of the muscle and increases the temperature range over which neurally evoked muscle relaxations can be elicited. Neurally evoked contractions are maximally potentiated by 5-HT at warm (18 degrees C) temperatures; however, 5-HT enhances excitatory junction potentials in a temperature-independent manner. Finally, 5-HT strongly increases resting muscle tension at the coldest extent of the temperature range tested (2 degrees C) but is ineffective at 22 degrees C. These data demonstrate that 5-HT elicits several temperature-dependent physiological changes in the passive and active responses of muscle to neural input. The overall effect of 5-HT is to increase the temperature range over which neurally evoked motor movements can be elicited in this neuromuscular system. PMID- 17337716 TI - Activation and nuclear translocation of ERK in response to ligand-dependent and independent stimuli in liver and gill cells from rainbow trout. AB - The mitogen-activated protein kinase ERK is an important signalling molecule involved in the control of cell proliferation, differentiation and cell death, targeting molecules at the cell membrane, in the cytosol, and in the nucleus. This study investigated the activation pattern and subcellular distribution of ERK in liver and gill cells of rainbow trout upon hypo-osmotic shock, addition of epidermal growth factor (EGF) and copper treatment. It further set out to characterize the hypothetical role of nuclear-export signal (NES)-dependent relocation of ERK after nuclear entry and the potential involvement of the ERK activator MEK. Although, in primary hepatocytes, ERK was activated in all conditions in a stimulus-specific manner, it did not accumulate in the nucleus, irrespective of the absence or presence of the inhibitor of NES-dependent export leptomycin B (LB). Similarly, in trout hepatoma cells, where pERK levels increased upon osmotic and mitotic stimulation, but not after toxic insult, no significant nuclear translocation was observed. In a gill cell line, levels of pERK increased after osmotic and mitotic stimulation and showed a decrease during incubation with a toxicant. Again, none of these conditions triggered nuclear accumulation of pERK in the gill cells in the absence of LB, but in contrast to the observation in liver cells, both osmotic and mitotic stimulation caused nuclear accumulation in the presence of the inhibitor. The ERK activator MEK, which possesses a NES-sequence, was apparently not involved in nuclear export, as it did not seem to enter the nucleus. Altogether, ERK is activated in trout cells in a stimulus- and cell type-specific manner, and our data suggest that it acutely acts primarily on cytoplasmic or membrane-situated targets in liver cells, whereas it presumably triggers rapid transcriptional activities in gill cells. PMID- 17337717 TI - Modulation of mandibular loading and bite force in mammals during mastication. AB - Modulation of force during mammalian mastication provides insight into force modulation in rhythmic, cyclic behaviors. This study uses in vivo bone strain data from the mandibular corpus to test two hypotheses regarding bite force modulation during rhythmic mastication in mammals: (1) that bite force is modulated by varying the duration of force production, or (2) that bite force is modulated by varying the rate at which force is produced. The data sample consists of rosette strain data from 40 experiments on 11 species of mammals, including six primate genera and four nonprimate species: goats, pigs, horses and alpacas. Bivariate correlation and multiple regression methods are used to assess relationships between maximum (epsilon(1)) and minimum (epsilon(2)) principal strain magnitudes and the following variables: loading time and mean loading rate from 5% of peak to peak strain, unloading time and mean unloading rate from peak to 5% of peak strain, chew cycle duration, and chew duty factor. Bivariate correlations reveal that in the majority of experiments strain magnitudes are significantly (P<0.001) correlated with strain loading and unloading rates and not with strain loading and unloading times. In those cases when strain magnitudes are also correlated with loading times, strain magnitudes are more highly correlated with loading rate than loading time. Multiple regression analyses reveal that variation in strain magnitude is best explained by variation in loading rate. Loading time and related temporal variables (such as overall chew cycle time and chew duty factor) do not explain significant amounts of additional variance. Few and only weak correlations were found between strain magnitude and chew cycle time and chew duty factor. These data suggest that bite force modulation during rhythmic mastication in mammals is mainly achieved by modulating the rate at which force is generated within a chew cycle, and less so by varying temporal parameters. Rate modulation rather than time modulation may allow rhythmic mastication to proceed at a relatively constant frequency, simplifying motor control computation. PMID- 17337718 TI - Characterization of very-low density lipoprotein particle diameter dynamics in relation to egg production in a passerine bird. AB - During avian egg production, oestrogen mediates marked increases in hepatic lipid production and changes in the diameter of assembled very-low density lipoprotein (VLDL). A nearly complete shift from generic VLDL ( approximately 70 nm in diameter), which transports lipids to peripheral tissues, to yolk-targeted VLDL (VLDLy) ( approximately 30 nm), which supplies the yolk with energy-rich lipid, has been observed in the plasma of laying domestic fowl. We validated an established dynamic laser scattering technique for a passerine songbird Taeniopygia guttata, the zebra finch, to characterize the dynamics of VLDL particle diameter distribution in relation to egg production. We predicted that non-gallinaceous avian species that have not been selected for maximum egg production would exhibit less dramatic shifts in lipid metabolism during egg production. As predicted, there was considerable overlap between the VLDL particle diameter distributions of laying and non-laying zebra finches. But unexpectedly, non-laying zebra finches had VLDL diameter distributions that peaked at small particles and had relatively few large VLDL particles. As a result, laying zebra finches, in comparison, had diameter distributions that were shifted towards larger VLDL particles. Nevertheless, laying zebra finches, like laying chickens, had larger proportions of particles within proposed VLDLy particle diameter ranges than non-laying zebra finches (e.g. sVLDLy: 50% vs 37%). Furthermore, zebra finches and chickens had similar modal (29.7 nm in both species) and median (32.7 nm vs 29.6 nm) VLDL particle diameters during egg production. Therefore, although zebra finches and chickens exhibited opposing directional shifts in VLDL particle diameter distribution during egg production, the modifications to VLDL particle structure in both species resulted in the realization of a common goal, i.e. to produce and maintain a large proportion of small VLDL particles of specific diameters that are capable of being incorporated into newly forming egg yolks. PMID- 17337719 TI - Does the metabolic rate-flight speed relationship vary among geometrically similar birds of different mass? AB - Based on aerodynamic considerations, the energy use-flight speed relationship of all airborne animals and aircraft should be U-shaped. However, measures of the metabolic rate-flight speed relationship in birds have been available since Tucker's pioneering experiments with budgerigars nearly forty years ago, but this classic work remains the only study to have found a clearly U-shaped metabolic power curve. The available data suggests that the energetic requirements for flight within this species are unique, yet the metabolic power curve of the budgerigar is widely considered representative of birds in general. Given these conflicting results and the observation that the budgerigar's mass is less than 50% of the next smallest species to have been studied, we asked whether large and small birds have metabolic power curves of different shapes. To address this question we measured the rates of oxygen uptake and wingbeat kinematics in budgerigars and cockatiels flying within a variable-speed wind tunnel. These species are close phylogenetic relatives, have similar flight styles, wingbeat kinematics, and are geometrically similar but have body masses that differ by a factor of two. In contrast to our expectations, we found the metabolic rate flight speed relationship of both species to be acutely U-shaped. We also found that neither budgerigars nor cockatiels used their normal intermittent flight style while wearing a respirometric mask. We conclude that species size differences alone do not explain the previously unique metabolic power curve of the budgerigar; however, due to the absence of comparable data we cannot evaluate whether the mask-related kinematic response we document influences the metabolic rate-flight speed relationship of these parrots, or whether the energetics of flight differ between this and other avian clades. PMID- 17337720 TI - TTX-sensitive and TTX-insensitive control of spontaneous gut motility in the developing zebrafish (Danio rerio) larvae. AB - Spontaneous regular gut motility in zebrafish begins around 4 days post fertilisation (d.p.f.) and is modulated by release of acetylcholine and nitric oxide. The role of intrinsic or extrinsic innervation for initiating and propagating the spontaneous contractions, however, is not well understood. By creating spatiotemporal maps, we could examine spontaneous motility patterns in zebrafish larvae in vivo at 4 and 7 d.p.f. in more detail. Tetrodotoxin (TTX) was added to elucidate the importance of nervous control. Anterograde and retrograde contraction waves originated in the same region, just posterior to the intestinal bulb. This area correlates well with the distribution of Hu (human neuronal protein C/D)-immunoreactive nerve cell bodies. Whereas numerous immunoreactive nerve cells were present in the mid and distal intestine at both 4 and 7 d.p.f., fewer cells were seen anterior to the origin of contractions. The overall frequency of contractions (1.16+/-0.15 cycles min(-1), N=14 at 4 d.p.f.; 1.05+/ 0.09 cycles min(-1), N=13 at 7 d.p.f.) and the interval between individual anterograde contraction waves (54.8+/-7.9 s at 4 d.p.f., N=14; 56.9+/-4.4 s, N=13 at 7 d.p.f.) did not differ between the two stages but the properties of the contractions were altered. The distance travelled by each wave increased from 591.0+/-43.8 microm at 4 d.p.f. (N=14) to 719.9+/-33.2 microm at 7 d.p.f. (N=13). By contrast, the velocity decreased from 4 d.p.f. (49.5+/-5.5 microm s(-1), N=12) to 7 d.p.f. (27.8+/-3.6 microm s(-1), N=13). At 4 d.p.f., TTX did not affect any of the parameters whereas at 7 d.p.f. anterograde frequency (control 1.07+/-0.12 cycles min(-1), N=8; TTX 0.55+/-0.13 cycles min(-1), N=8) and distance travelled (control 685.1+/-45.9 microm, N=8; TTX 318.7+/-88.7 microm, N=6) were decreased. In conclusion, enteric or extrinsic innervation does not seem to be necessary to initiate spontaneous contractions of the gut in zebrafish larvae. However, later in development, nerves have an increasingly important role as modulators of intestinal activity. PMID- 17337721 TI - The extensor tibiae muscle of the stick insect: biomechanical properties of an insect walking leg muscle. AB - We investigated the properties of the extensor tibiae muscle of the stick insect (Carausius morosus) middle leg. Muscle geometry of the middle leg was compared to that of the front and hind legs and to the flexor tibiae, respectively. The mean length of the extensor tibiae fibres is 1.41+/-0.23 mm and flexor fibres are 2.11+/-0.30 mm long. The change of fibre length with joint angle was measured and closely follows a cosine function. Its amplitude gives effective moment arm lengths of 0.28+/-0.02 mm for the extensor and 0.56+/-0.04 mm for the flexor. Resting extensor tibiae muscle passive tonic force increased from 2 to 5 mN in the maximum femur-tibia (FT)-joint working range when stretched by ramps. Active muscle properties were measured with simultaneous activation (up to 200 pulses s( 1)) of all three motoneurons innervating the extensor tibiae, because this reflects most closely physiological muscle activation during leg swing. The force length relationship corresponds closely to the typical characteristic according to the sliding filament hypothesis: it has a plateau at medium fibre lengths, declines nearly linearly in force at both longer and shorter fibre lengths, and the muscle's working range lies in the short to medium fibre length range. Maximum contraction velocity showed a similar relationship. The force-velocity relationship was the traditional Hill curve hyperbola, but deviated from the hyperbolic shape in the region of maximum contraction force close to the isometric contraction. Step-like changes in muscle length induced by loaded release experiments characterised the non-linear series elasticity as a quadratic spring. PMID- 17337722 TI - Feedback activation of ferrous 5-lipoxygenase during leukotriene synthesis by coexisting linoleic acid. AB - Ferrous lipoxygenases seem to be activated through a feedback control mechanism via FA hydroperoxides generated from PUFAs by partially existing ferric lipoxygenases. However, during leukotriene synthesis, feedback activation of ferrous 5-lipoxygenase in the presence of arachidonic acid (AA) was not observed. In the present study, we examined the feedback activation of ferrous 5 lipoxygenase in the 5-lipoxygenase/AA system in the presence of linoleic aicd (LA), which is a predominant component of membrane phospholipids. When potato 5 lipoxygenase was incubated with AA and LA in the presence of nitroxyl radical, 3 carbamoyl-2,2,5,5-tetramethyl-3-pyrroline-N-oxyl (CmDeltaP), one-electron redox cycle reaction between ferric and ferrous 5-lipoxygenase was detected. For each revolution of the cycle, one molecule of PUFA and one molecule of its hydroperoxide were converted into PUFA-allyl radical-CmDeltaP adduct ([PUFA-H]. CmDeltaP) and PUFA-epoxyallyl radical-CmDeltaP adduct ([PUFA-H+O].-CmDeltaP), respectively. The ratios, [AA-H].-CmDeltaP/[LA-H].-CmDeltaP and [AA-H+O]. CmDeltaP/[LA-H+O].-CmDeltaP, were estimated to be 1.7 and 0.13, respectively. These facts indicate that ferrous 5-lipoxygenase is activated through feedback control in the presence of LA, and that resulting ferric 5-lipoxygenase catalyzes the stoichiometric synthesis of leukotrienes from AA. In conclusion, the biosynthesis of leukotrienes is remarkably efficient. PMID- 17337723 TI - Indications for repair of full-thickness rotator cuff tears. AB - Rotator cuff repair surgery for full-thickness tears is common and accepted in orthopaedics today. Given that a significant number of people have asymptomatic rotator cuff tears, the indications for surgery are, however, somewhat unclear. Multiple factors such as duration of symptoms, acuity and size of the tear, patient age, and others require consideration and can influence the decision to perform surgery. This article reviews these variables and the indications for surgery to repair full-thickness rotator cuff tears. PMID- 17337724 TI - Displaced stress fracture of the femoral neck treated by valgus subtrochanteric osteotomy: 2 case studies. PMID- 17337725 TI - Avoiding allograft length mismatch during anterior cruciate ligament reconstruction: patient height as an indicator of appropriate graft length. AB - BACKGROUND: Given the increasing use of allografts in anterior cruciate ligament reconstruction, selection of appropriate-sized grafts may help individual surgeons as well as the efficiency of the overall system for graft distribution. HYPOTHESIS: Recipient patient height can predict the desired length for the tendinous portion of a patellar bone-tendon-bone allograft in anterior cruciate ligament reconstruction. STUDY DESIGN: Cohort study (Prognosis); Level of evidence, 2. METHODS: A series of 414 knees in 392 consecutive patients undergoing magnetic resonance imaging evaluation of knee pain were enrolled in the study. Data collected from magnetic resonance imaging included patella and patellar tendon length and intraarticular length of the anterior cruciate ligament. Patient age, height, weight, and gender were recorded. Linear regression analysis assessed the correlation between patient height and intraarticular length of the anterior cruciate ligament as well as patellar tendon length. The effect of variance in age, weight, and gender on anterior cruciate ligament intraarticular length was also measured. RESULTS: A strong positive correlation was found between intraarticular length of the anterior cruciate ligament and patient height (Pearson r = 0.73; P < .001). Anterior cruciate ligament length (y, in millimeters) as a function of height (x, in inches) can be expressed as y = 1.17x - 41.29. As a function of height (x, in centimeters), anterior cruciate ligament length (y, in millimeters) can be expressed as y = 0.4606x - 41.29. Age, gender, and weight did not significantly influence this relationship. A weak positive association was found between patient height and patellar tendon length. CONCLUSION: Patient height can predict the desired length of the tendinous portion of a patellar bone-tendon-bone allograft. An addition of 10 mm is made to the predicted anterior cruciate ligament length to allow for aperture tibial and femoral fixation. Patellar bone tendon-bone allografts can be requested based on recipient patient height as follows: 5 ft, 0 in to 5 ft, 6 in: tendinous length/total length, 45 mm/95 mm; 5 ft, 7 in to 6 ft, 1 in: 50 mm/100 mm; > 6 ft, 1 in: 55 mm/105 mm. PMID- 17337726 TI - Effectiveness of bioabsorbable arrows compared with inside-out suturing for vertical, reparable meniscal lesions: a randomized clinical trial. AB - BACKGROUND: Techniques for repairing the meniscus include both open and arthroscopic techniques using sutures and bioabsorbable implants. The purpose of this study was to compare the effectiveness of inside-out suturing and bioabsorbable arrows for repair of vertical meniscal lesions. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: One hundred consecutive patients were randomly assigned to arrows (n = 51) or sutures (n = 49). Sixty-five percent of patients (31 sutures, 34 arrows) underwent a concomitant anterior cruciate ligament reconstruction. A blinded research associate conducted assessments at 6 weeks and 3, 6, 12, and 24 months postoperatively. The primary outcome was retear rate. Secondary outcomes included the Western Ontario Meniscal Evaluation Tool, Anterior Cruciate Ligament Quality of Life Outcome Measure, and side-to-side comparisons of flexion and extension. RESULTS: At baseline, groups were similar in age, gender, time from injury to surgery, and length and location of tear. Mean follow-up was 28.0 +/- 8.4 months. There were 22 failed meniscal repairs (11 in each group), which did not represent a significant difference in the rate of failure between groups (P = .92). The mean quality of life scores and side-to-side differences in extension and flexion measurements were not significantly different between groups. Two patients from the arrow group crossed over into the suture group at the time of surgery because of technical difficulties with the device, and in 3 instances, a single suture was needed to keep the tear reduced while arrows were introduced. Two patients required reoperation for removal of a prominent, subcutaneous arrow, and 1 patient in the suture group suffered a transient peroneal nerve palsy during revision suturing. CONCLUSION: At intermediate follow-up, there were no statistically significant differences in measured outcomes between meniscal suturing and arrows. Longer term follow-up is necessary to identify differences between these 2 treatments, particularly to estimate the incidence of articular surface damage in patients whose meniscal tear was repaired using arrows. PMID- 17337727 TI - Fatty infiltration and atrophy of the rotator cuff do not improve after rotator cuff repair and correlate with poor functional outcome. AB - BACKGROUND: The role of degenerative changes in rotator cuff musculature with respect to the functional outcomes of rotator cuff repair have only recently been recognized and are still not well understood. In addition, the reversibility of these changes with repair of the tendons is questionable. HYPOTHESIS: Poorer preoperative muscle quality negatively affects outcome, and a successful outcome (in terms of a healed repair) might demonstrate improvements in fatty infiltration and muscle atrophy. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Thirty-eight patients (mean age, 62 years) were prospectively evaluated with preoperative and 1-year postoperative clinical examination and appropriate magnetic resonance image sequencing to determine grades of muscle atrophy and fatty infiltration of the supraspinatus and infraspinatus muscles. American Shoulder and Elbow Society (ASES), Constant, and pain scores were determined as well as strength measurements. The retear rate and progression of muscle degeneration were also evaluated. Independent predictors of outcome measurements and cuff integrity were determined. RESULTS: The overall clinical outcome, including ASES, Constant, and pain scores, improved significantly (P < .0001). Strength in forward elevation improved significantly (P < .006), while external rotation strength did not. There was a strongly negative correlation between muscle quality and outcome results in most cases. When the results were adjusted for multivariate effect, muscle atrophy and fatty infiltration of the infraspinatus muscle were the only independent predictors of ASES and Constant scores (P < .03). Tear size and rotator cuff healing did not play an independent role. Tear size, however, was the only independent predictor of ultimate cuff integrity (P = .002). Both atrophy and fatty infiltration progressed significantly over the course of the study. In cases in which the tendon had re torn, the progression was found to be more significant than when the repair proved successful (P < .003). CONCLUSION: Muscle atrophy and fatty infiltration of the rotator cuff muscles, particularly of the infraspinatus, play a significant role in determining functional outcome after cuff repair. Tear size appears to have the most influential effect on repair integrity. A successful repair did not lead to improvement or reversal of muscle degeneration and a failed repair resulted in significantly more progression. In general, healed repairs demonstrated minimal progression. These findings suggest that repairs should be performed, if possible, before more significant deterioration in the cuff musculature in order to optimize outcomes, and that understanding the degree of muscle atrophy and fatty infiltration before surgery can help guide patient expectations. PMID- 17337728 TI - Stress fracture of the distal phalanx of the great toe in a professional ballet dancer: a case report. PMID- 17337729 TI - Internal fixation of juvenile osteochondritis dissecans lesions of the knee. AB - BACKGROUND: Operative techniques for the management of juvenile osteochondritis dissecans lesions of the knee include drilling, internal fixation, fragment removal, and chondral resurfacing. PURPOSE: To evaluate the functional and radiographic outcome of internal fixation of juvenile osteochondritis dissecans lesions of the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The study design was a retrospective case series. Twenty-six knees in 24 skeletally immature patients underwent internal fixation of osteochondritis dissecans lesions. Mean follow-up was 4.25 years (range, 2-14.75 years). Mean patient age was 14.7 years (range, 11-16 years). There were 13 boys and 11 girls. Lesions were graded per the Ewing and Voto classification, with 9 stage II lesions (fissured), 11 stage III lesions (partially attached), and 6 stage IV lesions (detached). Methods of internal fixation included variable pitch screws (n = 11), bioabsorbable tacks (n = 10), partially threaded cannulated screws (n = 3), and bioabsorbable pins (n = 3). Mean follow-up was 4.25 years (range, 2.0 14.75 years). RESULTS: Healing occurred in 22 of 26 lesions (healing rate, 84.6%). There was no significant difference in healing rate for lesion location, fixation method, or lesion grade. In fact, all 6 stage IV (detached) lesions healed. The mean postoperative Lysholm score was 85.8, mean postoperative International Knee Documentation Committee score was 82.6, and mean postoperative Tegner activity level was 7.4. Mean time to healing was 6 months. Eight patients underwent additional procedures: 4 for nonunion, 1 for hemarthrosis, and 3 for elective screw removal. CONCLUSION: Given the relatively high healing rate, good functional outcome, and low complication rate, the authors advocate internal fixation of unstable juvenile osteochondritis dissecans lesions of the knee, even for detached lesions and in patients with a history of surgery for the osteochondritis dissecans lesion. PMID- 17337730 TI - Molecular basis of selectivity of nucleoside triphosphate incorporation opposite O6-benzylguanine by sulfolobus solfataricus DNA polymerase Dpo4: steady-state and pre-steady-state kinetics and x-ray crystallography of correct and incorrect pairing. AB - Previous work has shown that Sulfolobus solfataricus DNA polymerase Dpo4 catalyzed bypass of O(6)-methylguanine (O(6)-MeG) proceeds largely in an accurate but inefficient manner with a "wobble" base pairing between C and O(6)-MeG (Eoff, R. L., Irimia, A., Egli, M., and Guengerich, F. P. (2007) J. Biol. Chem. 282, 1456-1467). We considered here the bulky lesion O(6)-benzylguanine (O(6)-BzG) in DNA and catalysis by Dpo4. Mass spectrometry analysis of polymerization products revealed that the enzyme bypasses and extends across from O(6)-BzG, with C the major product ( approximately 70%) and some T and A ( approximately 15% each) incorporated opposite the lesion. Steady-state kinetic parameters indicated that Dpo4 was 7-, 5-, and 27-fold more efficient at C incorporation opposite O(6)-BzG than T, A, or G, respectively. In transient state kinetic analysis, the catalytic efficiency was decreased 62-fold for C incorporation opposite O(6)-BzG relative to unmodified DNA. Crystal structures reveal wobble pairing between C and O(6) BzG. Pseudo-"Watson-Crick" pairing was observed between T and O(6)-BzG. Two other structures illustrate a possible mechanism for the accommodation of a +1 frameshift in the Dpo4 active site. The overall effect of O(6)-BzG is to decrease the efficiency of bypass by roughly an order of magnitude in every case except correct bypass, where the effect is not as pronounced. By comparison, Dpo4 is more accurate but no more efficient than model replicative polymerases, such as bacteriophage T7(-) DNA polymerase and human immunodeficiency virus-1 reverse transcriptase in the polymerization past O(6)-MeG and O(6)-BzG. PMID- 17337731 TI - Key role for ceramides in mediating insulin resistance in human muscle cells. AB - Elevated non-esterified fatty acids, triglyceride, diacylglycerol, and ceramide have all been associated with insulin resistance in muscle. We set out to investigate the role of intramyocellular lipid metabolites in the induction of insulin resistance in human primary myoblast cultures. Muscle cells were subjected to adenovirus-mediated expression of perilipin or incubated with fatty acids for 18 h, prior to insulin stimulation and measurement of lipid metabolites and rates of glycogen synthesis. Adenovirus-driven perilipin expression lead to significant accumulation of triacylglycerol in myoblasts, without any detectable effect on insulin sensitivity, as judged by the ability of insulin to stimulate glycogen synthesis. Similarly, incubation of cells with the monounsaturated fatty acid oleate resulted in triacylglycerol accumulation without inhibiting insulin action. By contrast, the saturated fatty acid palmitate induced insulin resistance. Palmitate treatment caused less accumulation of triacylglycerol than did oleate but also induced significant accumulation of both diacylglycerol and ceramide. Insulin resistance was also caused by cell-permeable analogues of ceramide, and palmitate-induced resistance was blocked in the presence of inhibitors of de novo ceramide synthesis. Oleate co-incubation completely prevented the insulin resistance induced by palmitate. Our data are consistent with ceramide being the agent responsible for insulin resistance caused by palmitate exposure. Furthermore, the triacylglycerol derived from oleate was able to exert a protective role in sequestering palmitate, thus preventing its conversion to ceramide. PMID- 17337732 TI - Modular organization of the Sulfolobus solfataricus mini-chromosome maintenance protein. AB - Mini-chromosome maintenance (MCM) proteins form ring-like hexameric complexes that are commonly believed to act as the replicative DNA helicase at the eukaryotic/archaeal DNA replication fork. Because of their simplified composition with respect to the eukaryotic counterparts, the archaeal MCM complexes represent a good model system to use in analyzing the structural/functional relationships of these important replication factors. In this study the domain organization of the MCM-like protein from Sulfolobus solfataricus (Sso MCM) has been dissected by trypsin partial proteolysis. Three truncated derivatives of Sso MCM corresponding to protease-resistant domains were produced as soluble recombinant proteins and purified: the N-terminal domain (N-ter, residues 1-268); a fragment comprising the AAA+ and C-terminal domains (AAA+-C-ter, residues 269-686); and the C terminal domain (C-ter, residues 504-686). All of the purified recombinant proteins behaved as monomers in solution as determined by analytical gel filtration chromatography, suggesting that the polypeptide chain integrity is required for stable oligomerization of Sso MCM. However, the AAA+-C-ter derivative, which includes the AAA+ motor domain and retains ATPase activity, was able to form dimers in solution when ATP was present, as analyzed by size exclusion chromatography and glycerol gradient sedimentation analyses. Interestingly, the AAA+-C-ter protein could displace oligonucleotides annealed to M13 single-stranded DNA although with a reduced efficiency in comparison with the full-sized Sso MCM. The implications of these findings for understanding the DNA helicase mechanism of the MCM complex are discussed. PMID- 17337733 TI - Mechanisms that prevent template inactivation by HIV-1 reverse transcriptase RNase H cleavages. AB - The RNase H activity of human immunodeficiency virus, type 1 (HIV-1) reverse transcriptase (RT) cleaves the viral genome concomitant with minus strand synthesis. We previously analyzed RT-mediated pausing and RNase H cleavage on a hairpin-containing RNA template system and reported that RT generated 3' end directed primary and secondary cuts while paused at the base of the hairpin during synthesis. Here, we report that all of the prominent cleavage products observed during primer extension on this template correlated with pause induced cuts. Products that persisted throughout the reaction corresponded to secondary cuts, about eight nucleotides in from the DNA primer terminus. This distance allows little overlap of intact template with the primer terminus. We considered whether secondary cuts could inactivate further synthesis by promoting dissociation of the primer from the template. As anticipated, 3' end-directed secondary cuts decreased primer extendibility. This provides a plausible mechanism to explain the persistence of secondary cut products in our hairpin template system. Improving the efficiency of synthesis by increasing the concentration of dNTPs or addition of nucleocapsid protein (NC) reduced pausing and the generation of pause related secondary cuts on this template. Further studies reveal that 3' end-directed primary and secondary cleavages were also generated when synthesis was stalled by the presence of 3'-azido-3' deoxythymidine at the primer terminus, possibly contributing to 3'-azido-3' deoxythymidine inhibition. Considered together, the data reveal a role for NC and other factors that enhance DNA synthesis in the prevention of RNase H cleavages that could be detrimental to viral replication. PMID- 17337734 TI - Secondary exposure for 73 and 200 MeV proton therapy. AB - Following modifications on the beam line at the Orsay Protontherapy Center, dose measurements were performed in order to make a dose map in the treatment rooms and in the delimited radiation-controlled area around beam line. Measurements were performed using tissue-equivalent proportional counters and rem-counters. Analysis of TEPC single event measurements showed that high LET components (>10 keV.microm(-1)) represent 90 to 99% of total dose equivalent in the treatment rooms and 50 to 90% in the controlled area and quality factors range, respectively between 2 and 15. A fast neutron component was identified in the treatment rooms, where dose equivalent rate varied between few microSv.h(-1) to some dozen of mSv.h(-1). In high-energy radiation field rem-counters underestimated TEPC values for neutron component. The variation between instruments response according to the location is linked to energetic spectrum variations and instrument characteristics. PMID- 17337735 TI - Operational comparison of TLD albedo dosemeters and solid state nuclear tracks detectors in fuel fabrication facilities. AB - The authors carried out an operational study that compared the use of TLD albedo dosemeters and solid state nuclear tracks detector in plutonium environments of Japan Nuclear Cycle Development Institute, Tokai Works. A selected group of workers engaged in the fabrication process of MOX (Plutonium-Uranium mixed oxide) fuel wore both TLD albedo dosemeters and solid state nuclear tracks detectors. The TL readings were generally proportional to the counted etch-pits, and thus the dose equivalent results obtained from TLD albedo dosemeter agreed with those from solid state nuclear tracks detector within a factor of 1.5. This result indicates that, in the workplaces of the MOX fuel plants, the neutron spectrum remained almost constant in terms of time and space, and the appropriate range of field-specific correction with spectrum variations was small in albedo dosimetry. PMID- 17337736 TI - Potential of modern technologies for improvement of in vivo calibration. AB - In the frame of IDEA project, a research programme has been carried out to study the potential of the reconstruction of numerical anthropomorphic phantoms based on personal physiological data obtained by computed tomography (CT) and Magnetic Resonance Imaging (MRI) for calibration in in vivo monitoring. As a result, new procedures have been developed taking advantage of recent progress in image processing codes that allow, after scanning and rapidly reconstructing a realistic voxel phantom, to convert the whole measurement geometry into computer file to be used on line for MCNP (Monte Carlo N-Particule code) calculations. The present paper overviews the major abilities of the OEDIPE software studies made in the frame of the IDEA project, on the examples of calibration for lung monitoring as well as whole body counting of a real patient. PMID- 17337738 TI - Biokinetic modelling of natural thorium in humans by ingestion. AB - The retention of naturally occurring thorium (228Th, 230Th, 232Th) in model compartments and its daily urinary and faecal excretion after acute and chronic injections and ingestions were calculated for male and female subjects of six age groups based on the current age-dependent biokinetic model for thorium (Th) recommended by the International Commission on Radiological Protection (ICRP). The results are tabulated in a database. The calculated contents of 228,230,232Th in organs or tissues using their reference concentrations in foodstuffs for the European population are compared with autopsy data. The model prediction of 232Th in whole body for a 50-year-old unexposed person is 22 mBq, 86% of that in skeleton, 9.7% in other soft tissues, 3.4% in liver, 0.7% in kidneys and 0.01% in blood. The modelling predicts lower contents of the natural Th isotopes in whole body, especially in blood compared with measured data for the unexposed public. Modelled 232Th daily urinary excretions are 5 to 10 times less than bio-assay data from the authors' own laboratory. PMID- 17337739 TI - Quality assurance of personal beta particle dosemeters used for individual monitoring of occupationally exposed persons. AB - As a result of investigations and intercomparison measurements organised from 1996 to 1999 by PTB, several types of personal dosemeters, all based on TLD, were selected by the dosimetry services for the measurement of the personal dose equivalent Hp(0.07) in beta and/or photon radiation fields. These dosemeters have now the status of legal personal beta partial-body dosemeters. Workplaces at which beta radiation might significantly contribute to the doses to the extremities are to be found today with increasing frequency in radiation therapy, radiation source production and nuclear power plants. Quality assurance for beta personal dosemeters is stipulated by guidelines for the official dosimetry service and is carried out by way of the intercomparison measurements organised periodically by the PTB. The results are evaluated based on the recommendations of the German Commission on Radiological Protection (SSK). The procedure of these intercomparison measurements will be explained in detail. The experience gained from three series of comparisons with seven types of fingerring dosemeters will be described and the results will be presented. The anonymity of the dosemeter types and of the participants in the intercomparison will be preserved. PMID- 17337740 TI - Worldwide bioassay data resources for plutonium/americium internal dosimetry studies. AB - Biokinetic models are the scientific underpinning of internal dosimetry and depend, ultimately, for their scientific validation on comparisons with human bioassay data. Three significant plutonium/americium bioassay databases, known to the authors, are described: (1) Sellafield, (2) Los Alamos and (3) the United States Transuranium Registry. A case is made for a uniform standard for database format, and the XML standard is discussed. PMID- 17337741 TI - Relation between organ and whole body doses and local doses measured by ESR for standard and realistic neutron and photon external overexposures. AB - In the case of a radiological accident due to external exposure, the assessment of the organs and whole body dose received by the victim is fundamental information for therapeutic strategy. Two complementary dosimetric techniques based on physical means are used in routine practice in the laboratory: Monte Carlo (MC) calculations and ESR spectroscopy performed on materials removed from the victim. The aim of the present study is to provide data relevant for a quick assessment of the dose distribution in case of accidental overexposure using dose ESR measurements performed on one or several points of the body. The chosen configurations were, on the one hand, standard homogeneous exposures (ICPR 74) and, on the other hand, exposures typical of accidental situations (source at 1m, in a pocket, in a hand and contaminated floor). The study was performed for monoenergetic photons and neutrons, and several sources (60Co, 137Cs, 192Ir, 252Cf and AmBe). PMID- 17337742 TI - Standards, documents of relevance and directives in individual monitoring: is European individual monitoring in compliance with standards? AB - Individual monitoring services (IMS) in Europe do not comply with the same legal or approval requirements. Anyway, a degree of harmonisation existing in individual monitoring practices in Europe has been achieved mainly thanks to documents as standards or international recommendations, which with different weight represent invaluable vehicles of condensed information transfer. However, implementation of standards is not straightforward and harmonisation is not directly a consequence. Somehow, 'harmony' is needed also in standards: IEC and ISO standards, on performance requirements for dosemeters sometimes have different approaches (i.e. performance criteria). Moreover, standards do not all refer to reliability, and therefore being in compliance with standards does not by itself assure that dose results are reliable. Standards are not the only reference documents for an IMS. EURADOS working group on 'Harmonisation of Individual Monitoring in Europe', who has been active in the years 2001-2004, suggested a classification of publication on individual monitoring, distinguishing between standards and documents of relevance, which can be both national and international. None of the two categories are mandatory unless specified in legislation. The Council Directive 96/29/EURATOM and its implementation in each EU Member States has fostered harmonisation of the approach (i.e. approval of dosimetric services) and of the reference quantities for individual monitoring within EU, but national legislation still allow substantial differences in individual monitoring from country to country. PMID- 17337743 TI - Response of neutron detectors to high-energy mixed radiation fields. AB - Radiation protection around CERN's high-energy accelerators represents a major challenge due to the presence of complex, mixed radiation fields. Behind thick shielding neutrons dominate and their energy ranges from fractions of eV to about 1 GeV. In this work the response of various portable detectors sensitive to neutrons was studied at CERN's High-Energy Reference Field Facility (CERF). The measurements were carried out with conventional rem counters, which usually cover neutron energies up to 20 MeV, the Thermo WENDI-2, which is specified to measure neutrons up to several GeV, and a tissue-equivalent proportional counter. The experimentally determined neutron dose equivalent results were compared with Monte Carlo (MC) simulations. Based on these studies field calibration factors can be determined, which result in a more reliable estimate of H*(10) in an unknown, but presumably similar high-energy field around an accelerator than a calibration factor determined in a radiation field of a reference neutron source. PMID- 17337744 TI - Monte Carlo study of a 60Co calibration field of the Dosimetry Laboratory Seibersdorf. AB - The gamma radiation fields of the reference irradiation facility of the Dosimetry Laboratory Seibersdorf with collimated beam geometry are used for calibrating radiation protection dosemeters. A close-to-reality simulation model of the facility including the complex geometry of a 60Co source was set up using the Monte Carlo code MCNP. The goal of this study is to characterise the radionuclide gamma calibration field and resulting air-kerma distributions inside the measurement hall with a total of 20 m in length. For the whole range of source detector-distances (SDD) along the central beam axis, simulated and measured relative air-kerma values are within +/-0.6%. Influences on the accuracy of the simulation results are investigated, including e.g., source mass density effects or detector volume dependencies. A constant scatter contribution from the lead ring-collimator of approximately 1% and an increasing scatter contribution from the concrete floor for distances above 7 m are identified, resulting in a total air-kerma scatter contribution below 5%, which is in accordance to the ISO 4037-1 recommendations. PMID- 17337745 TI - Imaging the brain activity changes underlying impaired visuospatial judgments: simultaneous FMRI, TMS, and behavioral studies. AB - Damage to parietal cortex impairs visuospatial judgments. However, it is currently unknown how this damage may affect or indeed be caused by functional changes in remote but interconnected brain regions. Here, we applied transcranial magnetic stimulation (TMS) to the parietal cortices during functional magnetic resonance imaging (fMRI) while participants were solving visuospatial tasks. This allowed us to observe both the behavioral and the neural effects of transient parietal activity disruption in the active healthy human brain. Our results show that right, but not left, parietal TMS impairs visuospatial judgment, induces neural activity changes in a specific right-hemispheric network of frontoparietal regions, and shows significant correlations between the induced behavioral impairment and neural activity changes in both the directly stimulated parietal and remote ipsilateral frontal brain regions. The revealed right-hemispheric neural network effect of parietal TMS represents the same brain areas that are functionally connected during the execution of visuospatial judgments. This corroborates the notion that visuospatial deficits following parietal damage are brought about by a perturbation of activity across a specific frontoparietal network, rather than the lesioned parietal site alone. Our experiments furthermore show how concurrent fMRI and magnetic brain stimulation during active task execution hold the potential to identify and visualize networks of brain areas that are functionally related to specific cognitive processes. PMID- 17337746 TI - Neurofilament protein and neuronal activity markers define regional architectonic parcellation in the mouse visual cortex. AB - This study was designed to assess the chemoarchitectural organization and extent of the mouse visual cortex. We used nonphosphorylated neurofilament protein, a neuronal marker that exhibits region-specific cellular and laminar patterns, to delineate cortical subdivisions. A comprehensive analysis demonstrated that pyramidal and nonpyramidal neurons expressing neurofilament proteins display striking laminar and regional patterns in the mouse visual cortex permitting the delineation of the primary visual cortex (V1) and its monocular and binocular zones, 2 lateral, and 5 medial extrastriate cortical areas with clear anatomical boundaries and providing evidence that the mouse medial extrastriate cortex is not homogeneous. We also investigated the expression profiles of 2 neuronal activity markers, the immediate early genes c-fos and zif-268, following deprivation paradigms to ascertain the visual nature of all subdivisions caudal, medial, and lateral to V1. The present data indicate that neurochemically identifiable subdivisions of the mouse visual cortex exist laterally and medially to V1 and reveal specific anatomical and functional characteristics at the cellular and regional levels. PMID- 17337747 TI - Alternating and postictal psychoses: review and a unifying hypothesis. AB - A comparison of the clinical and pathophysiological features of postictal psychosis and brief interictal or alternating psychosis was undertaken to examine if the underlying mechanisms are distinct in these 2 conditions. A selective review of the published literature in English on epilepsy and brief psychosis was carried out. The literature indicates that even though brief postictal and alternating psychoses are considered to be separate syndromes, they have a number of similarities. It can be argued that the underlying pathomechanisms are common, with the brain's inhibitory processes in response to seizures playing a key role in the development of the psychosis. These homeostatic mechanisms manifest as electrophysiological, cerebral blood flow, and neurotransmitter and receptor changes. Both syndromes are likely to be associated with prolonged inhibition in limbic circuits, with further seizures modifying the psychosis depending upon whether it is associated with disinhibition or hypersynchrony involving enhanced inhibition. The neurotransmitter with a key role is GABA, although ionic currents, catecholamines, opiates, adenosine, glutamate, and nitric oxide play a role. Brief postictal and alternating psychoses provide an opportunity to understand the complex relationships between epilepsy and schizophrenia-like brief psychotic episodes, and this understanding can assist in their management. PMID- 17337748 TI - Substance use and abuse in first-episode psychosis: prevalence before and after early intervention. AB - Despite the high prevalence of substance abuse among first-episode psychosis (FEP) populations, few studies examine whether early intervention (EI) improves substance abuse. OBJECTIVE: To examine the prevalence and pattern of substance use and abuse among an FEP sample over 12 months. METHODS: All the participants were diagnosed with a first episode of a schizophrenia spectrum disorder. The participants were followed prospectively. The prevalence rates of substance use and abuse from this sample were compared before and after 12 months of EI services and were compared with rates observed in a sample from the general population. RESULTS: A total of 200 participants (80.0% males; mean age 24 years) entered the study: 183 participants completed all the assessments at baseline, 131 participants completed all the assessments at 12 months. At baseline, the findings showed similar prevalence rates between the FEP sample and the general sample for lifetime cannabis use (60% vs 55%, respectively) and hazardous alcohol use (26% vs 21%) but significantly different prevalence rates for lifetime hallucinogen (29% vs 15%; P < .001) and cocaine use (20% vs 14%; P < .001). At 12 months, the prevalence rates for drug abuse (P < .01), hazardous alcohol use (P < .01), and concurrent drug abuse and hazardous alcohol use (P < .05) were significantly lower than at baseline. CONCLUSION: Substance use and abuse decreased significantly after 12 months of EI services; EI services may be able to detect and to reduce substance use among FEP patients before it becomes a more serious disorder. PMID- 17337749 TI - Visualization of extensor digitorum tenosynovitis with three-dimensional ultrasonography. PMID- 17337751 TI - No B cells--no active RA? Advances in B cell depletion in RA--repeated therapy under conditions of clinical practice. PMID- 17337750 TI - Trends in economic consequences of rheumatoid arthritis over two subsequent years. AB - OBJECTIVE: To examine changes in direct costs and in working status over 2 yrs in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: In both 1999 and 2000, RA patients (n = 461) filled out a questionnaire retrospectively regarding utilization of health care, other RA-related direct costs and working status. Patients were categorized into four disease duration groups: 0-2 yrs, 2-6 yrs, 6 10 yrs and >10 yrs. At the same time points, disease activity was assessed. Logistic regression analyses were performed to identify a possible association between disease activity (high >66th percentile) measured at start of the second year and high direct costs (high >66th percentile) in the second year. RESULTS: Compared with the first year, a significant decrease in the costs for contacts with health care workers and for costs for laboratory tests was observed in the second year for the <2 yrs group. In the 2-6 yrs group and the >10 yrs group, we found a significant decrease in costs for devices and adaptations, but medication costs increased in the <2 yrs and the >10 yrs group in the second year. In the >10 yrs group, this was mainly due to an increasing number of patients who started to use biological agents during the second year. In all four disease duration groups, worse Visual Analogue Scale (VAS) disease activity and VAS general well-being were significantly associated with high direct costs. Of 97 patients working without disability at time of the first assessment, 12 (12%) patients became (partial) work disabled during follow-up. CONCLUSION: In particular, costs for devices/adaptations and for medication changed during follow-up. The latter was probably due to an increase in the use of biological agents. Hopefully a decrease in direct costs and a reduced percentage of patients getting work disabled by better disease control will outweigh the high costs of biological drugs in the future. PMID- 17337752 TI - Flowering and determinacy in maize. AB - All plant organs are produced by meristems, groups of stem cells located in the tips of roots and shoots. Indeterminate meristems make an indefinite number of organs, whereas determinate meristems are consumed after making a specific number of organs. Maize is an ideal system to study the genetic control of meristem fate because of the contribution from determinate and indeterminate meristems to the overall inflorescence. Here, the latest work on meristem maintenance and organ specification in maize is reviewed. Genetic networks, such as the CLAVATA components of meristem maintenance and the ABC programme of flower development, are conserved between grasses and eudicots. Maize and rice appear to have conserved mechanisms of meristem maintenance and organ identity. Other pathways, such as sex determination, are likely to be found only in maize with its separate male and female flowers. A rich genetic history has resulted in a large collection of maize mutants. The advent of genomic tools and synteny across the grasses now permits the isolation of the genes behind inflorescence architecture and the ability to compare function across the Angiosperms. PMID- 17337753 TI - Gene expression and target tissue dose in the rat epidermis after brief JP-8 and JP-8 aromatic and aliphatic component exposures. AB - Exposures of jet propulsion fuel 8 (JP-8) to human and laboratory animal skin have resulted in skin irritation. JP-8 is a mixture of aromatic and aliphatic hydrocarbons, which in some cases have also been shown to be irritating to the skin. In an attempt to determine if aromatic or aliphatic components could mimic the JP-8-induced gene expression response, we exposed rats to JP-8, undecane (UND), tetradecane (TET), trimethylbenzene (TMB), and dimethylnaphthalene (DMN) for 1 h and examined the epidermis to characterize the gene expression response. We also measured the concentrations of the JP-8 components in the epidermis with gas chromatography/mass spectrometry after 1-h exposures to JP-8 and pure components to determine if differences in potency could be identified. Changes in gene expression, compared to sham treatment, were studied with microarray techniques and analyzed for changes in gene ontology categories. UND and TMB exposures caused the greatest number of changes in transcript levels compared to DMN and TET. When only the specific functional and signaling pathways that were changed by JP-8 were considered, these pathways were nearly all activated by the components, but to different extents. After pure component exposures, the epidermal concentrations of the components showed no significant differences, although the differences in magnitude of either total or pathway-specific gene expression differed by a factor of 10-fold. We conclude that no single component that we studied mimicked the gene expression resulting from the JP-8 exposure but that UND had the most similar responses. These data suggest that there are differences in potency between the four components studied. PMID- 17337754 TI - Genistein accumulates in body depots and is mobilized during fasting, reaching estrogenic levels in serum that counter the hormonal actions of estradiol and organochlorines. AB - Isoflavones are important dietary compounds that are consumed with the daily diet and elicit important biological actions. Here we report on the ability of genistein to partially accumulate in body depots of male mice, be released following fasting, and modulate the actions of estradiol and environmental estrogens in reproductive and nonreproductive target organs of estrogen-reporter mice (ERE-tK-luciferase). After the consumption of 50 mg/kg/day for 3 days, genistein accumulates in body compartments where it remains at functionally active levels for at least 15 days. Following 48 h of fasting, its concentration increased in serum from 99 +/- 13 to 163 +/- 17 nM. These levels are sufficient to exert an estrogenic effect in the testis and liver, as revealed by a twofold increase in luciferase gene expression. beta-Benzene-hexachloride (betaBHC) given at the concentration of 100 mg/kg/day for 3 days also accumulates in the body and is released by fasting, reaching serum levels of 176 +/- 33 nM, upregulating the luciferase gene in the liver and inhibiting its expression in the testis. When genistein was given in combination with betaBHC at doses sufficient to induce accumulation of both in body depots, the genistein mobilized by fasting reversed the action of the mobilized betaBHC in the testis. Acute administration of nutritional doses of genistein inhibited the action of estradiol and reversed the antiestrogenic action of o,p'-DDT: 1,1,1,-trichloro-2(p-chlorophenyl)-2-(o chlorophenyl)ethane in the liver and the antiestrogenic action of betaBHC in the testis. Genistein had an additive effect with the ER agonist p,p'-DDT: 1,1,1, trichloro-2,2-bis(p-chlorophenyl)ethane in the liver. The observed effects may be relevant to a protective action of phytoestrogens against estrogen receptor interacting pollutants as well as the dietary modulation of estradiol action. PMID- 17337755 TI - The utility of an international sera bank for use in evaluating the potential human allergenicity of novel proteins. AB - In the safety assessment of novel foods produced through biotechnology, careful consideration is given to determining the allergenic potential of newly introduced proteins. IgE serum screening is one tool for evaluating whether the protein in question has sequence identity to a known allergen or if the source of the gene encoding the protein is a known allergenic food. A "specific" serum screen involves testing a gene product with sera from patients with documented clinical allergy to a specific allergen to confirm that the gene product of interest is not the same protein to which the patient produces IgE antibodies. A "targeted" serum screen involves testing the gene product of interest with sera from patients sensitive to food or aeroallergens from the same broad group. The concept of a global sera bank with accessible, well-characterized sera for use in such assays is an appealing option. This paper summarizes the consensus elements from a workshop to evaluate the potential utility of an international sera bank for evaluating the allergenicity of novel proteins. Areas of agreement following the workshop included the following: (1) specific sera screens are appropriate for exploring potentially cross-reactive proteins that have been identified through bioinformatics analyses; however, additional validation is needed, particularly for targeted sera screens, (2) practical and ethical considerations may preclude the formation of a global sera bank, and therefore, (3) a regional network of clinicians who could serve as sources of patient sera or be approached to conduct sera studies would be the most practical alternative. PMID- 17337756 TI - The relation between patterns of vacation sun exposure and the development of acquired melanocytic nevi in German children 6-7 years of age. AB - Sun exposure is the main environmental risk factor for the development of melanocytic nevi. Although the general association is not disputed, the interplay between intense intermittent and the cumulative amount of sun exposure in defining the promoting effect on melanocytic nevus development is an area of debate. Trained staff members ascertained total body counts of melanocytic nevi in a cross-sectional study of 2,189 children 6-7 years of age who were recruited in two German centers in 2002. Their parents provided information about a variety of exposure factors. The distribution of melanocytic nevi was skewed markedly to the right; therefore, a negative binomial regression model provided the appropriate framework for a multivariable analysis. A steep gradient with respect to the (adjusted) number of melanocytic nevi was apparent only for the frequency of vacation episodes associated with sun exposure in areas with an intense ultraviolet radiation. In contrast, no such gradients were found for the cumulative duration of vacation sun exposure in such areas or for any variable related to vacation sun exposure in areas with a low ultraviolet radiation. This observation supports the hypothesis that intermittent exposure to high doses of ultraviolet radiation plays an especially important role in nevus development. PMID- 17337757 TI - Age and menopausal effects of hormonal birth control and hormone replacement therapy in relation to breast cancer risk. AB - It is unclear whether breast cancer risk varies by age and menopausal status in relation to use of hormonal birth control (HBC) and hormone replacement therapy (HRT), taken singly or cumulatively. The authors utilized data from 1,478 cases and 1,493 controls aged 20-98 years with known menopausal status, who had participated in a population-based, case-control study conducted on Long Island during 1996-1997. Exogenous hormone use over the lifecourse was assessed by use of memory aids. The authors examined associations among women in these subgroups: premenopausal (n = 968), postmenopausal <65 years (n = 1,045), and postmenopausal > or = 65 years (n = 958). Among premenopausal women, risk was increased for ever use of HBC (odds ratio (OR) = 1.37, 95% confidence interval (CI): 1.04, 1.81) or HRT (OR = 1.81, 95% CI: 1.17, 2.81) and was pronounced among women reporting use of both HBC and HRT (OR = 2.59, 95% CI: 1.50, 4.46), long-term HRT use (OR = 3.93, 95% CI: 1.43, 10.84), or estrogen-plus-progestin therapy (OR = 3.51, 95% CI: 1.45, 8.49). There was no effect of ever HBC use among postmenopausal women aged less than 65 years, but risk was modestly elevated for more than 5 years of HRT use (OR = 1.41, 95% CI: 1.00, 1.99). Among postmenopausal women aged 65 years or more, odds ratios for HBC or HRT use were around the null. These results emphasize that timing of exogenous hormone use is important. Women who used these hormones before menopause had elevated risks, but the harmful effects began to decline with age after menopause. PMID- 17337758 TI - Evidence of increased secretion of apolipoprotein B-48-containing lipoproteins in subjects with type 2 diabetes. AB - Patients with type 2 diabetes have high levels of triglyceride-rich lipoproteins (TRLs), including apolipoprotein B-48 (apoB-48)-containing TRLs of intestinal origin, but the mechanism leading to overaccumulation of these lipoproteins remains to be fully elucidated. Therefore, the objective of this study was to examine the in vivo kinetics of TRL apoB-48 and VLDL, intermediate density lipoprotein (IDL), and LDL apoB-100 in type 2 diabetic subjects (n = 11) and nondiabetic controls (n = 13) using a primed-constant infusion of l-[5,5,5 D(3)]leucine for 12 h in the fed state. Diabetic subjects had significantly higher fasting glycemia, higher fasting insulinemia, higher plasma triglyceride, and lower HDL-cholesterol levels than controls. Compared with controls, diabetic subjects had increased TRL apoB-48, VLDL apoB-100, and IDL apoB-100 pool sizes as a result of increased production rates (PRs) and reduced fractional catabolic rates of these lipoprotein subfractions. Furthermore, multiple linear regression analyses revealed that the diabetic/control status was an independent predictor of TRL apoB-48 PR and represented nearly 35% of its variance. These results suggest that the overaccumulation of TRLs seen in patients with type 2 diabetes is attributable to increased PRs of both intestinally derived apoB-48-containing lipoproteins and TRL apoB-100 of hepatic origin and to decreased catabolism of these subfractions. PMID- 17337759 TI - Use of celecoxib immediately post marketing in Canada: acute or chronic pain? AB - OBJECTIVES: The diffusion of innovations theory suggests that early users of innovations influence others. This study was undertaken to apply the diffusion of innovations theory to the prescribing of celecoxib and to determine if prescriber and patient characteristics differed amongst early use of celecoxib for acute pain versus chronic musculoskeletal conditions. METHODS: Using Manitobaas population-based prescription and health care databases, diffusion time from market availability to first prescription for celecoxib was determined for each prescriber. The diffusion of prescribing curves for celecoxib in acute pain versus chronic musculoskeletal conditions were compared. Separately for acute and chronic conditions, the likelihood of being an early or late prescriber or user of celecoxib was determined according to physician factors (specialty and place of training) and patient demographics. This multivariate analysis was completed using polytomous logistic regression, with majority prescribers as the reference. RESULTS: The use of celecoxib for chronic musculoskeletal conditions demonstrated faster diffusion than for acute pain. The majority of early use of celecoxib was for chronic conditions; however 36% of first prescriptions were for acute pain, including the treatment of back pain and injuries. Early prescribers of celecoxib for acute pain were more likely than majority prescribers to be general practitioners (OR = 2.24, 95%CI: 1.53-3.29) and have hospital affiliations (OR=1.54, 95%CI: 1.04-2.27). Early users of celecoxib for chronic conditions were less likely to be low income (OR=0.56, 95%CI: 0.35-0.91). CONCLUSIONS: Immediately after market release in Canada, celecoxib was commonly prescribed for the treatment of acute pain; these prescriptions were associated with general practitioners and hospital affiliation status. PMID- 17337760 TI - Immunology in Pittsburgh. AB - The University of Pittsburgh School of Medicine has a long tradition of excellence in immunology research and training. Faculty, students, and postdoctoral fellows walk through hallways that are pictorial reminders of the days when Dr. Jonas Salk worked here to develop the polio vaccine, or when Dr. Niels Jerne chaired the Microbiology Department and worked on perfecting the Jerne Plaque Assay for antibody-producing cells. Colleagues and postdoctoral fellows of Professor Salk are still on the faculty of the University of Pittsburgh Medical School as are graduate students of Professor Jerne. A modern research building, the 17 story high Biomedical Science Tower, is a vivid reminder of the day when Dr. Thomas Starzl arrived in Pittsburgh and started building the most prominent solid-organ-transplant program in the world. The immunology research that developed around the problem of graft rejection and tolerance induction trained numerous outstanding students and fellows. Almost 20 yr ago, the University of Pittsburgh founded the University of Pittsburgh Cancer Institute (UPCI) with the renowned immunologist Dr. Ronald Herberman at its helm. This started a number of new research initiatives in cancer immunology and immunotherapy. A large number of outstanding young investigators, as well as several well-established tumor immunologists, were recruited to Pittsburgh at that time. PMID- 17337762 TI - Antitumor activity of NK cells. AB - NK cells have been shown to play an important role in the lungs with regards to tumor cell clearance and resistance of this organ to metastases. Here, we have investigated whether NK cells play a similar role in organs other than the lungs. We conclude that while organ-resistance to metastases correlates well with the NK activity of the host, a clear correlation between NK activity and clearance of tumor cells is found only in the lungs. We also demonstrate that activation of NK cells with the TLR 3 ligand poly I:C results in a substantial increase in the number of organ-associated NK cells. This increase may explain the increased resistance to metastasis seen in many organs after poly I:C treatment. Finally, we present data showing that NK cells activated ex vivo with IL-2 are able to localize to lung tumors following iv adoptive transfer and to significantly reduce the tumors they infiltrate. We conclude that NK cells, which currently are under intense investigation owing to their newly discovered immunoregulatory functions, remain very potent antitumor killer cells capable of killing not only circulating tumor cells, but also well-established micro metastases. PMID- 17337761 TI - Apoptosis and autoimmunity. AB - Cell death by apoptosis plays a significant and seemingly contradictory role in the development and pathogenesis of autoimmune diseases. Apoptosis is integral to the assembly and maintenance of a healthy, self-tolerant immune system. However, many of the molecular and cellular events specific to apoptosis generate a reservoir of self-antigens with the potential to initiate and possibly perpetuate autoimmune conditions. Recent findings that support this latter, more sinister role for apoptosis have shed light on a mystery that is common to many systemic autoimmune diseases, namely, why the majority of autoantibodies produced in patients with these diseases target proteins that are normally found inside the cell, often within the nucleus. This review will discuss how autoantigens are specifically altered during the apoptotic process, and how the complement system participates in recognizing and clearing these potentially immunogenic packages. PMID- 17337763 TI - From B cell to plasma cell: regulation of V(D)J recombination and antibody secretion. AB - B cell development culminates in the formation of plasma cells, potent secretors of the immunoglobulins (Ig), proteins crucial for the health of the organism. Two distinctive and crucial steps are required during B cell differentiation. First, variable gene segments encoding the antigen-binding region of Ig undergo directed rearrangement through a process known as V(D)J recombination. Second, alternative processing of the Ig heavy chain mRNA transcript enables plasma cells to secrete high levels of Ig protein. This review focuses on the molecular mechanisms that control V(D)J recombination in B cell progenitors and alternative RNA processing in plasma cells. PMID- 17337764 TI - Mechanisms of minor histocompatibility antigen immunogenicity: the role of infinitesimal versus structurally profound polymorphisms. AB - Minor histocompatibility antigens (mHAgs) are a diverse collection of major histocompatibility complex (MHC)-bound peptides that play a critical role in the induction of detrimental graft-versus-host disease (GVHD) or the development of beneficial graft-versustumor (GVT) effects after allogeneic hematopoietic stem cell transplantation. mHAgs are a consequence of allelic polymorphism that translates to disparity in MHC-presented peptide epitopes between transplant donor and recipient. This donor/recipient allelic disparity can range from infinitesimal amino side chain differences between MHC-presented peptides, to profound structural polymorphisms in genes and proteins that can nullify transcription or translation of one allelic variant and result in the complete abrogation of its presentation by MHC. PMID- 17337765 TI - CD161B:ClrB interactions mediate activation of enhanced lysis of tumor target cells following NK cell:DC co-culture. AB - Co-culture of natural killer (NK) cells and dendritic cells (DCs) results in their reciprocal co-activation, and an enhancement of lysis of tumor target cells. The receptor:ligand pairings mediating this enhancement are unknown. Therefore, we investigated whether interactions of CD161, on NK cells, with Clrs, on DCs, might have a role in this effect. Blocking expression of CD161B using siRNA resulted in a reduction in enhanced lytic activity following NK:DC co culture. Conversely, blocking expression of CD161F with siRNA had no effect on enhanced lytic function following NK:DC co-culture. Blocking expression of ClrB/Ocil, a ligand for CD161B, resulted in a reduced level of enhanced lytic function following NK:DC co-culture. This is the first report of NK receptors responsible for interaction with DCs having a role in mediating enhanced lytic function following NK:DC interactions. PMID- 17337766 TI - Dissecting the humoral immune response to simian immunodeficiency virus: mechanisms of antibody-mediated virus neutralization. AB - The ultimate goal of an AIDS vaccine is to elicit potent cellular and humoral immune responses that will result in broadly enduring protective immunity. During the past several years, we have focused on characterizing the quantitative and qualitative properties of the antibody response, principally working to define the mechanism(s) of antibody-mediated neutralization in vitro. We have utilized a panel of monoclonal antibodies generated from monkeys infected with attenuated SIV for more than 8 mo to dissect the early events of virus infection involved in antibody-mediated neutralization. Presented herein are highlights from our studies that have identified potential mechanisms by which antibodies neutralize SIV in vitro. PMID- 17337767 TI - CCR7 mediates inflammation-associated tumor progression. AB - Chemokine receptor 7 (CCR7) mediates leukocyte adhesion and chemotaxis from peripheral sites of inflammation through lymphatic channels to secondary lymphoid organs. Aberrant CCR7 expression has been identified on certain tumor types and been linked to pro-survival and invasive pathways. In metastatic squamous cell carcinoma of the head and neck (SCCHN), we have described the selective upregulation of functional CCR7. In this manuscript, we review our understanding of CCR7-mediated signaling in metastatic SCCHN and provide evidence for its involvement in tumor survival, invasion, and metastasis. Autocrine and paracrine CCR7 activation appears to propagate the response to the CCR7 ligands CCL19 and CCL21, which are expressed by the lymphatic endothelium, secondary lymphoid tissues, and CCR7-positive tumor cells. Based on our recent findings, the induction of CCR7 expression and the sustenance of the autocrine signaling pathway have been shown to be regulated by NF-kappaB, similar to several types of immune cells. While extending these observations to metastatic SCCHN tumor cells, our studies highlight the importance of downstream NF-kappaB mediated CCR7 signals in the progression of SCCHN malignancy. PMID- 17337768 TI - Human tumor antigens, immunosurveillance, and cancer vaccines. AB - Cancer is a serious health problem as well as a scientific challenge. A lot has been learned about the process of transformation of a normal cell into a tumor cell by studying genes and proteins that regulate this process either in cis or in trans. However, whether these molecular mechanisms succeed in fulfilling their potential to give a clinically evident disease depends in great measure on the host response to those molecular changes. The work of my laboratory aims to provide evidence in animal models as well as in cancer patients that immune system can control cancer growth and that this important function can be improved through vaccination with well-defined tumor antigens. PMID- 17337769 TI - Gene therapy for type 1 diabetes: is it ready for the clinic? AB - This review, in addition to updating the growing list of type 1 diabetes- relevant gene therapies, offers an outline of short-term objectives that can readily be met to move, at least, adenoviral and adeno-associated viral-based protocols into the clinic, first as a means of facilitating islet allografts as well as platforms with which to introduce immunoregulatory transgenes. A wide array of genes have been tested to restore insulin production, to drive the differentiation of insulin-producing progenitors, and to confer immunosuppression in an antigen- and tissue-restricted manner. PMID- 17337770 TI - Adenosine-mediated inhibition of cytotoxic activity and cytokine production by IL 2/NKp46-activated NK cells: involvement of protein kinase A isozyme I (PKA I). AB - Adenosine suppresses the production of various cytokines/ chemokines and inhibits the cytotoxic activity of murine and human NK cells activated with IL-2 or Ly49D, NKp46-receptor crosslinking, respectively. These effects are mediated by the type A2A adenosine receptor via stimulation of adenylyl cyclase, increased production of cAMP, and activation of PKA. PKA I, but not PKA II, participates in the inhibitory effects of adenosine. Blocking regulatory, but not catalytic, subunits of PKA I abrogates the inhibitory effects of adenosine. These findings suggest that tumor-produced adenosine inhibits the activity of NK and other effector cells and thereby protects tumors from immune-mediated destruction. PMID- 17337771 TI - Induction of T cell immunity by cutaneous genetic immunization with recombinant lentivector. AB - Recent studies suggest that T cell-based cellular immunity plays an important role in preventing and delaying progression of infectious and neoplastic diseases. Based on these findings, recent efforts in vaccine research are giving rise to a new generation of "T cell" vaccines. The development of T cell vaccines has been problematic. Current investigations are focusing on gene-based immunization strategies, including the development of non-viral "naked" plasmid DNA and recombinant viral vector-based genetic immunization approaches. Here, we briefly review recent progress in the development of recombinant viral vectors for genetic immunization and our own recent studies elucidating differences in mechanisms of genetic immunization. We propose that the mechanism of immune induction depends in part on unique features of specific viral vectors, and that a comparison of representative vectors mechanistically will enable a more informed understanding of the determining parameters of immune induction. Our initial studies have focused on the identification of antigen-presenting-cell subsets important for priming CD8+ T cell immunity, the effects of antigen persistence on immune responses, and the unique immunogenicity of skin as a target tissue for vaccine delivery. We review data suggesting that the unique properties of recombinant lentivectors make them appealing candidates as genetic immunization vehicles for eliciting T cell immune responses. PMID- 17337772 TI - A triple entente: virus, neurons, and CD8+ T cells maintain HSV-1 latency. AB - Herpes simplex virus type 1 (HSV-1) travels by retrograde transport to sensory ganglia where latency is established. Recurrent disease results from virus reactivation and anterograde transport to nerve termini. Prevention of reactivation requires a complex interplay among virus, neuron, and immune response. Study of this tripartite relationship suggests possible interaction, and even communication among these components, that direct an immune response that allows for control of virus while preserving the viability of host tissue. Exciting new evidence supports the view that CD8+ effector T cells employ both lytic granule-dependent and interferon gamma-dependent effector mechanisms in maintaining HSV-1 latency. PMID- 17337773 TI - Professional antigen-presenting cells of the skin. AB - The skin functions as an important pro-inflammatory and immune organ. Accordingly, the epidermis and dermis are highly populated by dendritic cells (DC), which are potent antigen-presenting cells (APC) with important immunostimulatory and migratory activities. Whereas the biological characteristics and immunological functions of epidermal DC known as Langernahs cells (LC) have been the focus of intense research in the past, less is known regarding their dermal counterparts named dermal dendritic cells (DDC). Although it has been widely accepted that LC are the more relevant skin-resident APC, recent experimental evidence challenges this concept and proposes a different role for these important cell populations. In this article we compile recent scientific advances regarding the function of different skin-resident DC and we try to reconcile the new observations with the previously established paradigm. PMID- 17337774 TI - Helper roles of NK and CD8+ T cells in the induction of tumor immunity. Polarized dendritic cells as cancer vaccines. AB - The work in our laboratory addresses two interrelated areas of dendritic cell (DC) biology: (1) the role of DCs as mediators of feedback interactions between NK cells, CD8+ and CD4+ T cells; and (2) the possibility to use such feedback and the paradigms derived from anti-viral responses, to promote the induction of therapeutic immunity against cancer. We observed that CD8+ T cells and NK cells, the classical "effector" cells, also play "helper" roles, regulating ability of DCs to induce type-1 immune immunity, critical for fighting tumors and intracellular pathogens. Our work aims to delineate which pathways of NK and CD8+ T cell activation result in their helper activity, and to identify the molecular mechanisms allowing them to induce type-1 polarized DCs (DC1s) with selectively enhanced ability to promote type-1 responses and anti-cancer immunity. The results of these studies allowed us and our colleagues to design phase I/II clinical trials incorporating the paradigms of DC polarization and helper activity of effector cells in cancer immunotherapy. PMID- 17337775 TI - Immune regulation by the TIM gene family. AB - Recent studies have demonstrated that proteins of the T cell immunoglobulin and mucin domain (TIM) family are important regulators of immune function. Here we discuss the functional effects of TIM proteins on immune responses, how the effects of TIM proteins may be modulated by interactions with ligands and the limited information available on intracellular signals downstream of TIM proteins. PMID- 17337776 TI - New insights into mathematical modeling of the immune system. AB - In order to understand the integrated behavior of the immune system, there is no alternative to mathematical modeling. In addition, the advent of experimental tools such as gene arrays and proteomics poses new challenges to immunologists who are now faced with more information than can be readily incorporated into existing paradigms of immunity. We review here our ongoing efforts to develop mathematical models of immune responses to infectious disease, highlight a new modeling approach that is more accessible to immunologists, and describe new ways to analyze microarray data. These are collaborative studies between experimental immunologists, mathematicians, and computer scientists. PMID- 17337777 TI - Dendritic cell immunotherapy for autoimmune diabetes. AB - Dendritic cells (DC) play important roles in the initiation of immune responses and maintenance of self-tolerance. We have been studying the role of DC in the pathogenesis of type 1 diabetes and exploring the ability of specific DC subsets to prevent diabetes in non-obese diabetic (NOD) mice. DC subsets that prevent diabetes in this model have a mature phenotype and induce the production of regulatory Th2 cells. We review here recent advances in this area and highlight the importance of optimizing culture conditions and purification methods in the isolation of therapeutic DC. PMID- 17337778 TI - Pneumocystis colonization, airway inflammation, and pulmonary function decline in acquired immunodeficiency syndrome. AB - As a result of improved diagnosis, treatment, and supportive care for HIV infected patients, AIDS in developed countries has now become a chronic infection with prolonged survival time, but longterm complications are increasing contributors to morbidity and mortality. HIV-infected patients are at increased risk for the development of pulmonary complications, including chronic obstructive pulmonary disease (COPD); however, the mechanisms associated with this increased susceptibility have not been defined. Infectious agents may contribute to the development of COPD by upregulating inflammatory mediators in the lung that act in concert with cigarette smoke to promote lung pathology. Studies in human subjects and non-human primate models of AIDS suggest that the inflammatory response to asymptomatic carriage or colonization by the opportunistic pathogen, Pneumocystis sp. (Pc), is similar to that of COPD, which is characterized by influx of CD8+ T cells, neutrophils, and macrophages into the lungs. We have shown a high frequency of Pc colonization among asymptomatic HIV infected subjects and in non-HIV infected subjects with COPD. To investigate the role of Pc in the progression of obstructive lung disease in HIV infections, we developed a non-human primate model of Pc colonizatoin and infection in simian immunodeficiency virus (SIV)-infected macaques. These animals develop a prolonged colonization state characterized by a persistent influx of CD8+ T cells and neutrophils, and local increases in IL-8, IFN-gamma, and TNF-alpha. SIV-infected Pc-colonized monkeys show progressive decline in pulmonary function compared to SIV-infected monkeys. We hypothesize that in the context of AIDS-immune dysfunction, Pc colonization induces inflammatory responses leading to changes in pulmonary function and architecture similar to that seen in emphysema. Information gained from these studies will lead to the development of interventions to prevent lung injury associated with Pc colonization and the development of HIV-associated COPD. PMID- 17337779 TI - Dissecting genetic control of autoimmunity in NOD congenic mice. AB - My lab investigates genetic control of autoimmune disease and autoimmune phenotypes using a series of nonobese diabetic (NOD) congenic mice. NOD congenic mice have regions from B6/B10 introgressed onto the NOD genetic background, which reduces the severity/incidence of autoimmune diabetes. We have demonstrated, however, that while diabetes is reduced, other autoimmune phenotypes and diseases arise in NOD congenic mice. Mapping the genomic regions responsible for these phenotypes has produced novel insights into genetic control of autoimmunity. This review will illustrate some of the genetically controlled phenotypes we have investigated, which shed light upon autoimmune features relevant to human type 1 diabetes, systemic lupus erythematosus, and primary biliary cirrhosis. PMID- 17337781 TI - Dynamic properties of antigen uptake and communication between dendritic cells. AB - We have examined mechanisms of antigen uptake by dendritic cells (DC). While multiple experimental approaches have been used, live cell imaging has been especially informative, and is reviewed here. DC were shown to bind to and internalize bacteria, but not inert particles, demonstrating an unexpected selectivity that included sensing of secreted bacterial products and subsequent cell activation. This led to the observation that induced calcium fluxes in these cells could be propagated to other cells via thin membrane connections termed tunneling nanotubules that were shown to form an extensive network between cells, and are also present in other cell types. These data are discussed in terms of DC function, and also demonstrate the power of live cell imaging in elucidating complex biological phenomena that are not readily revealed using static imaging approaches or by biochemical analyses. PMID- 17337780 TI - Complement-mediated activation of the adaptive immune responses: role of C3d in linking the innate and adaptive immunity. AB - C3d is the final degradation product of the third component of complement (C3). When conjugated to an antigen, C3d enhances immune responses to the fused antigen. Therefore, this molecule has been used as an adjuvant to enhance the immune responses to various foreign and self-proteins. C3d binds to the complement receptor 2 (CR2) that is located on the surface of follicular dendritic cells (FDC), B cells, and T cells in many species. C3d stimulates antigen presentation by FCD and helps to maintain immunological B cell memory. On B cells, C3d interaction with CR2 will collect molecules such as CD19, TAPA (CD81), and Lew 13. CD19 has a long intracellular tail that triggers a signaling cascade that results in cell activation and proliferation. Furthermore, simultaneous C3d-CR2 ligation and surface immunoglobulin (sIg) by antigen, activates two signaling pathways that cross-talk and synergize to activate B cells. However, C3d can enhance antibody titers in the absence of CR2 binding, indicating CR2-independent mechanism(s) of enhancement of the immune response. This review focuses on the complexity of the C3d-CR2 interaction, the importance of this interaction for the enhancement of the immune response by C3d and its derivatives, as well as the paradoxical enhancement of the immune response in the absence of CR2. PMID- 17337782 TI - Age-dependent alterations of the T cell repertoire and functional diversity of T cells of the aged. AB - The aging immune system is characterized by the contraction of T cell receptor (TCR) diversity and the de novo expression of NKrelated receptors (NKR) on oligoclonal T cells. NKR+ T cells likely represent a secondary immune diversification as a biological adaptation of aging to ensure host defense despite shrinkage of the TCR repertoire. NKRs are expressed in various combinations even among TCR-identical cells, and are capable of triggering effector pathways in either TCR-independent or TCR-dependent fashion. Understanding the biology of NKR+ T cells will be pivotal to the development of strategies to enhance immunity in the elderly. PMID- 17337783 TI - MUC1 in endometriosis and ovarian cancer. AB - Endometriosis is a chronic, debilitating disease, associated with pelvic pain and infertility. Recent epidemiological studies suggest that women with endometriosis are at increased risk for ovarian cancer. Although the causative factors for both endometriosis and ovarian cancer remain largely unknown, several similarities between the proposed etiology of ovarian cancer and the observed pathophysiology of endometriosis have been reported. MUC1 glycoprotein is present in endometriotic lesions and overexpressed in epithelial ovarian tumors. We are currently studying immunity to MUC1 antigen in newly emerging preclinical models for endometriosis and ovarian cancer and exploring the potential for immune therapy/prevention with MUC1 in both diseases. PMID- 17337784 TI - Deciphering the complexity of acute inflammation using mathematical models. AB - Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics. PMID- 17337785 TI - Human tumor-derived vs dendritic cell-derived exosomes have distinct biologic roles and molecular profiles. AB - Microvesicles (MV) or exosomes are produced and secreted by tumor and normal cells. The molecular profile and functions of tumor-derived vs dendritic cell (DC)-derived MV are distinct. The former express death ligands and mediate apoptosis of activated T cells. The latter promote CD4+ T cell proliferation and may play a role in regulating T cell responses. Serving as intercellular communication networks, tumor-derived MV contribute to tumor escape, while DC derived MV drive and regulate immune response. PMID- 17337786 TI - HLA antibody analysis: sensitivity, specificity, and clinical significance in solid organ transplantation. AB - The clinical relevance of humoral allosensitization has gained a lot of attention in the last few years. An increasing number of studies have demonstrated adverse graft survival in patients who have either preformed or post-transplant-developed anti-HLA antibodies. The detection of HLA antibodies and the specificity analysis have evolved over time from primarily cell-based to solid-phase methods, including the availability of single-HLA antigen preparations. These technological advances combined with a better understanding of the epitope structure of HLA antigens have provided a more efficient, structurally based strategy to determine HLA compatibility. In conclusion, these emerging approaches can be reliably used to predict crossmatch results in highly sensitized patients and also to monitor the development of clinically relevant anti-HLA antibody after transplantation. PMID- 17337787 TI - Understanding and exploiting dendritic cells in human immunodeficiency virus infection using the nonhuman primate model. AB - Dendritic cells (DC) are pivotal cells in the innate immune system. Recent interest in the role of DC in human immunodeficiency virus (HIV) pathogenesis has increased with the finding that both myeloid (mDC) and plasmacytoid DC (pDC) are lost from blood during infection, associated with progression to disease. DC are also being studied intensively for their capacity to stimulate robust virus specific immunity as vaccines. Here we discuss our work in these contrasting fields of DC biology using the rhesus macaque nonhuman primate model. We focus on studies of DC dynamics in lymphoid tissues during pathogenic simian immunodeficiency virus (SIV) infection, DC trafficking in health and disease, DC based vaccination and the use of autologous virus as antigen for stimulation of virus-specific T cells. PMID- 17337788 TI - The molecular mechanisms that control function and death of effector CD4+ T cells. AB - This review features two areas of our research interests. First, our laboratory is interested in elucidating the molecular mechanisms that control generation, effector function, and fate of TH1 cells during inflammatory responses. We have been particularly interested in the role of the growth arrest and DNA damage inducible protein 45 (GADD45) gene family in TH1-mediated immune responses. We and others have shown that, in TH1 cells, Gadd45b and Gadd45g are induced by TCR signaling or IL-12 and IL-18. Gadd45b and Gadd45g are very important for the activation of p38 MAP kinases in TH1 cells and for effector functions of TH1 cells. We have found that deletion of Gadd45b and Gadd45g genes in mice results in a drastically reduced number of TH1 cells against Listeria monocytogenes. The critical role of Gadd45b and Gadd45g in TH1 responses in this acute infectious model has led us to hypothesize that they promote TH1-mediated autoimmune diseases. We therefore decided to test this hypothesis in experimental allergic encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Expecting low numbers of TH1 cells, we were surprised to see that Gadd45b deletion resulted in exacerbated chronic phase of EAE. In contrast to the reduction of TH1 cells we saw in acute L. monocytogenes infection, during the chronic phase of EAE we observed increased TH1 cells in the inflamed CNS when Gadd45b was deleted. Gadd45b deletion also resulted in enlarged spleens in older mice. Gadd45b/Gadd45g greatly enlarged spleens in older mice compared with Gadd45b single deletion. The enlargement of spleens was due to the accumulation of CD4+ T cells with an activated phenotype and B cells. In addition, we have found that Gadd45b and Gadd45g inhibit proliferation and promote apoptosis of activated CD4+ T cells. Therefore, Gadd45b and Gadd45g play a critical role as a molecular "doubleedged sword" in TH1-type immune responses to ensure a prompt, robust but self-limiting TH1 response. The second area of research in our laboratory focuses on the role of autophagy in T cells. We have recently discovered that autophagy is induced in TH1 and TH2 cells. There are more effector TH2 cells than TH1 cells that undergo autophagy. We have used RNAi strategy to "knockdown" autophagy in TH2 cell lines and found that autophagy is required for growth factor-withdrawal cell death. PMID- 17337790 TI - Heroes and great ideas column: crossing borders: Dr. Kwaku Ohene-Frempong. PMID- 17337791 TI - The role of lawyers in improving access to care. PMID- 17337792 TI - Oral health is the measure of a just society. AB - Former Surgeon General David Satcher's report, Oral Health in America, documents the higher burden of oral diseases and conditions borne by those with relatively low social standing at each stage of life. When an entire community suffers from a health concern, that concern becomes a social justice issue. Racial and ethnic minorities, prisoners, and seniors suffer disproportionately from oral diseases and conditions due to societal prejudices that place them at risk over and above any risk associated with their economic means. Community-based delivery models that involve the community in planning and implementation, build upon the existing health safety net to link oral health services with primary care, and change public or institutional policy to support the financing and delivery of oral health care have proven successful. Here we champion the need for a national health plan that includes oral health care to promote social justice and oral health for all. PMID- 17337793 TI - The Community Wellness Program: an intergenerational seminar for African Americans. PMID- 17337794 TI - Development of a church-based cancer education curriculum using CBPR. PMID- 17337795 TI - Cultural competency in New Jersey: evolution from planning to law. PMID- 17337796 TI - African American veterans' experiences with mobile geriatric care. AB - To explore perspectives concerning use of a mobile geriatrics unit (MGU) by underserved populations in low-income urban neighborhoods, we recruited 18 elderly African American patients and engaged them in in-depth semistructured interviews. Using grounded theory techniques of constant comparative analysis, we found that most patients learned about the MGU from community members and initially visited it to determine whether it would be worth using in the future. In describing their MGU experiences, patients tended to focus on three main factors: quality of care, accessibility of services, and ambience of the care setting. They reported that the MGU allowed them to have their health conditions and medications monitored regularly and functioned as a central link to the larger Veterans Affairs health care system. The findings suggest that using MGUs is an acceptable and effective way to help medically underserved populations receive primary medical care and referrals to specialty care. PMID- 17337797 TI - Racial/ethnic disparities in symptom severity among children hospitalized with asthma. AB - Asthma is the most common chronic illness among U.S. children as well as a leading cause of hospitalization and functional disability. This cross-sectional study uses 2001 hospitalization data for Pennsylvania to examine disparities among Black, Hispanic, and White children in asthma symptomatology at the time of admission. Compared with Whites, Black children were over twice as likely to have the most severe asthma symptoms, taking into account age, sex, insurance status, income, and rural/urban residence. Increased likelihood of severe clinical condition at admission was also independently associated with Medicaid coverage, with older age at admission, and with urban residence. The relationship between symptom severity at presentation in the emergency department and access to and utilization of appropriate ambulatory care services for children with asthma warrants further investigation. PMID- 17337798 TI - Knowledge, attitudes, and behaviors of hepatitis B screening and vaccination and liver cancer risks among Vietnamese Americans. AB - Hepatitis B Virus (HBV) infection is a serious health problem among Asian Americans. Vietnamese Americans are disproportionately affected by liver cancer compared with other racial and ethnic groups. Vietnamese males have the highest incidence of liver cancer of any racial group; incidence of liver cancer among Vietnamese males is 11 times higher than among White males. Nearly 80% of liver cancer is attributed to HBV. This study measured knowledge, attitudes, and behaviors related to HBV screening and vaccination. The study was conducted among 256 Vietnamese Americans in the greater Philadelphia and New Jersey area, with a large number of underserved, recent immigrants with low socioeconomic status and limited English proficiency. Participants were recruited from Vietnamese community-based organizations. Overall, 46.3% of the sample had heard of HBV or knew about the availability of screening (32.6%) or vaccination (35.5%) while 7.5% were ever screened and 6.3% had been vaccinated. Community-based, culturally appropriate interventions for Vietnamese Americans and health care providers should increase screening and vaccination rates. PMID- 17337799 TI - Quality in medical translations: a review. AB - Despite a growing number of U.S. citizens who do not speak English fluently, little literature attends to issues of accurate translation of medical documents. We conducted a systematic review of the World Wide Web and electronic library resources to identify sources on translating clinical and medical research documents. We identified and carefully examined 44 relevant articles. Each article was coded with 5 to 10 key words that were used as a guide when we searched the articles for issues salient to assuring quality in medical translations. We divided these into two major categories, mechanics/practicalities of translating medical documents and extrinsic factors influencing medical translations. The results of this review confirm that medical translation is a complex process involving far more than mechanically converting one language to another. Attention to translation procedures can improve the quality of care for limited English proficient patients. PMID- 17337800 TI - Attitudes of African American and low socioeconomic status white women toward medical research. AB - Minority and low socioeconomic status women are under-represented in clinical research due to logistical, informational, attitudinal, and sociocultural barriers. The primary objective of this study was to explore factors associated with research participation among African American and low socioeconomic status White women using the Theory of Planned Behavior. A secondary goal was to assess differences in barriers to research participation by age and race. A combination of qualitative (focus groups) and quantitative (trust scale) methodologies was employed. Ten focus groups were held, organized by age and race. Content analysis revealed three predominant themes: fear, distrust, and hope. Older women had higher trust; there was no difference in trust by race. The results suggest that women have conflicting feelings about research that cross ethnic lines and should be addressed by researchers. Effective strategies for overcoming barriers and increasing representation are those that establish ongoing relationships with relevant communities. PMID- 17337801 TI - Factors that influence the acceptability of collecting in-home finger stick blood samples in an urban, low-income population. AB - OBJECTIVES: To examine the acceptability of non-medical, community-based interviewers obtaining blood samples during in-home interviews from low-income study participants. METHODS: Two separate focus groups were conducted, one with ten non-medical community-based interviewers and the other with eight research participants from a low-income population. (Both the interviewers and the research participants had previously taken part in a research project over the course of five years.) RESULTS: Participants and interviewers were comfortable with finger stick blood samples performed in the home. The interviewers felt that adequate training was critical. Participants identified key issues: blood would not be used for other purposes and that the interviewers would be trained to handle blood safely. Both groups felt that it was crucial to communicate the study purpose and results. Recommendations from the focus groups were implemented and the acceptance rate for blood sampling was 99.5% (205/206). CONCLUSION: Proper training of interviewers, organization of supplies, and communication with participants can be combined to maximize acceptance of in-home, finger stick blood sample collection by community-based interviewers among a low-income population. PMID- 17337802 TI - Evaluation of breast cancer care under Puerto Rico's Health Care Reform. AB - Puerto Rico has implemented Health Care Reform legislation that shifted medically indigent and underserved persons from direct care by public sector institutions to managed care arrangements through the private sector. Our aim is to assess how previously underserved women with breast cancer have fared during the first three years of the Reform. Medical claims data were obtained on breast cancer cases in San Juan who were either enrolled in the capitated Reform plan or in a commercial policy offered by the same insurer. A set of indicators reflecting initial therapy, use of key services, and cumulative utilization rates of various medical procedures were constructed. Statistical tests were conducted to assess whether these indicators differed between Reform- and commercially-insured patients. Failure to reject null hypotheses of indicator differences were then used to judge Reform progress. We found some differences, but they were neither pervasive nor unidirectional. On balance, we conclude that previously underserved women are being treated for breast cancer roughly on par with other patients. This conclusion, however, is preliminary and subject to important qualifications. PMID- 17337803 TI - The costs of non-insurance in Maryland. AB - OBJECTIVES: This study calculates expenditures and costs related to a lack of health insurance coverage in the State of Maryland. RESEARCH METHODS: The study is based on detailed primary and secondary data collection on the following sources of payment and care related to non-insurance: (1) uncompensated hospital care; (2) other public subsidies; (3) ambulatory services; (4) philanthropic spending; and (5) uninsured individuals' costs. RESULTS: Expenditures by and for the uninsured in Maryland total $1.47 billion dollars. On a per-capita basis, this is equivalent to $2,371 per full-year uninsured person in the state. Twenty seven percent of this total, or $633 per uninsured person, is paid directly by the uninsured themselves in out-of-pocket medical expenditures. The state and local governments spent $497 per uninsured person (21% of the total), and the federal government spent an additional $401 (17%). Private payers (including insurance, physicians, and philanthropy) accounted for $460 (19%). CONCLUSIONS: The sources and flows of spending on the uninsured are complex, and these expenditure levels should not be interpreted as savings that would directly result from an expansion of insurance coverage. Our results are consistent with earlier studies completed at the national level, and add considerable detail. PMID- 17337804 TI - Using NAMCS to characterize the urban health care safety net. AB - PURPOSE: Data from the National Ambulatory Medical Care Survey (NAMCS) have been used to describe many facets of ambulatory care, but have been underutilized in their application to the urban health care safety net. Our interest was in comparing the visit characteristics of inner city primary care practices in New York City with those of the rest of the country. METHODS: Data were collected in 15 primary care centers affiliated with the New York City Research & Improvement Networking Group (NYC RING), a practice-based research network. Physicians completed the cross-sectional survey after patient visits using a slightly augmented version of the standard NAMCS form. Results were then compared with a subset of the Centers for Disease Control and Prevention's public-use dataset for the 2002 NAMCS, selecting only visits to primary care providers and practices in metropolitan statistical areas (N=8,598). Variables of primary interest were visit lengths and diagnoses, adjusting for age and sex. RESULTS: Physicians in NYC RING collected data on 1,861 encounters. Compared with the national sample, our clinicians see 140% more diabetes visits, 70% more hypertension, and 90% more asthma, and provide 88% more dermatologic care and over 300% more reproductive health services. Visits were, on average, one minute longer in our inner city practices (p<.05), and were generally longer across all diagnosis categories than in the national sample. CONCLUSIONS: The prevalence of metabolic syndrome and environmentally-related conditions and the provision of more than average specialty care characterize safety net care in New York City. PMID- 17337805 TI - Hearing handicap among adult residents of an urban homeless shelter. AB - This retrospective study was undertaken to identify the prevalence of hearing loss in the homeless population and its implications for vocational rehabilitation. Audiometric threshold data for adult residents of an urban homeless shelter were collected and reported. Subjects with hearing loss were identified and defined by their binaural high-frequency pure tone average (B HFPTA). Those subjects were assigned a predicted Hearing Handicap Inventory for Adults-Screener (HHIA-S) score. Their HHIA-S scores, in turn, were used to predict hearing handicap and hearing aid candidacy. Significant hearing handicap was predicted for 35.6% of subjects; 10.6% were identified as hearing aid candidates. These findings have implications for vocational rehabilitation that have not been previously addressed. PMID- 17337806 TI - Hospitalized younger: a comparison of a national sample of homeless and housed inpatient veterans. AB - BACKGROUND: Homelessness is associated with high rates of hospitalizations and age-adjusted mortality. Few studies have examined whether homeless people are admitted to the hospital at an earlier age than the general population or for different diagnoses. METHODS: We compared the age at admission and the primary discharge diagnoses in a national sample of 43,868 hospitalized veterans. RESULTS: The difference in median age between homeless and housed inpatients ranged from 10-18 years for medical-surgical diagnoses and 3-4 years for psychiatric and substance abuse diagnoses (p#.005 for all diagnoses). Homeless veterans were more likely to have been admitted for psychiatric and substance abuse diagnoses (79.9%), compared with housed veterans (29.1%). CONCLUSIONS: Substance abuse and psychiatric illness account for the majority of admissions among homeless veterans. Among all diagnostic groups, homeless people were admitted at younger ages. Our findings suggest that homeless people have either a more rapid disease course, leading to earlier morbidity, or lower admission threshholds sufficient to generate hospital admission. PMID- 17337807 TI - Prevalence of major depressive episodes in rural women using primary care. AB - Women carry a disproportionate burden of depression in part because situational and other factors enhance their risk. Rural women may be at particular risk because of poverty and lack of treatment opportunities. For this study we investigated the rate of current major depressive episodes (MDE) in impoverished rural women seeking care in a community health center (CHC) in the rural South. We screened 982 women for MDE during a routine primary care visit: about half were positive for depressive symptoms. Of women positive at screening, 194 were then assessed for psychiatric disorder. A current MDE was observed in 14.3% of women screened for depression and 72.2% of women assessed for psychiatric disorder. Recognizing that neither of these percentages reflects the likely rate of MDE among the larger population of rural impoverished women, we used probability theory and binary logistic regression to estimate a depression rate that could be applied as one factor associated with unmet need in this population of women. We estimate that 44.3% of the population of women using the CHC had MDE. These findings underscore the need for mental health services in rural primary care, especially in facilities serving impoverished women. PMID- 17337808 TI - Community characteristics and violence against homeless women in Los Angeles County. AB - Research on violence against homeless women has focused mainly on individual rather than community-level risk factors. Using an ecological conceptual framework, we estimated the independent association of community characteristics with sexual and physical assault in a probability sample of 974 homeless women. Participants were interviewed at 66 assistance programs in Los Angeles County, California in 1997. Individual responses were linked to community-level data from land use files and the U.S. Census by the facility ZIP codes. Multivariate logistic regression analysis showed that women using service providers in closer proximity to Skid Row had higher odds of physical assault (OR=1.48; 95% CI=1.03, 2.14). A number of individual characteristics were also associated with violent victimization. To reduce violence against homeless women, ensuring the safety of locations for shelters and other assistance programs should be a planning priority for local housing authorities. PMID- 17337810 TI - Differences in varicella-zoster virus seroepidemiology between temperate and tropical regions. PMID- 17337811 TI - The possible link between infections and atherosclerosis. PMID- 17337812 TI - A simple and effective approach to pemphigus. PMID- 17337813 TI - Seroprevalence of varicella zoster virus infections in Colombo district, Sri Lanka. AB - BACKGROUND: Although Varicella Zoster virus (VZV) infections occur worldwide, the epidemiology is remarkably different in tropical and temperate climates. VZV infections result in significant morbidity and mortality among adults in Sri Lanka. AIMS: For future VZV vaccination strategies, we set to determine the age specific seroprevalence rate of VZV infections in Colombo, Sri Lanka. MATERIALS AND METHODS: The study was carried out from 1999 to 2000. Multi-stage cluster sampling technique was used to collect 913 blood samples, which were tested for the presence of VZV-specific IgG antibodies. RESULTS: VZV seroprevalence rates were markedly lower in all age groups when compared to temperate climates. The seroprevalence rates increased with age in both the rural and urban populations. Of those aged 60 years, only 50% in the rural population and 78.9% in the urban population were immune to VZV. Seroprevalence rates of VZV infections were significantly different between the urban and rural populations (P< 0.001), with VZV-specific IgG antibodies detected in 47.5% in the urban population and 27.9% in the rural population. It was found that 56.2% (131) of females of childbearing age were nonimmune to VZV. CONCLUSIONS: These findings highlight the need for a VZV vaccination program, which is likely to have a huge impact on the incidence of chickenpox and its associated morbidity and mortality. PMID- 17337814 TI - Concurrent increased high sensitivity C-reactive protein and chronic infections are associated with coronary artery disease: a population-based study. AB - BACKGROUND: An elevated serum level of C-reactive protein (CRP) is an independent predictor of coronary artery disease (CAD). Chronic infections have also been implicated in the pathogenesis of CAD. AIMS: To investigate how concomitant chronic infection and CRP related to electrocardiogram-defined CAD in a general population. SETTING AND DESIGN: A population-based cross-sectional study, which was conducted in three Iranian ports in the northern Persian Gulf. MATERIALS AND METHODS: For evaluation of CAD, we used Minnesota coding criteria of a 12-lead resting electrocardiogram in 1,754 subjects, aged 25 years and over, selected by cluster random sampling. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae (C. pneumoniae), Herpes simplex virus type 1 (HSV-1), Helicobacter pylori (H. pylori) and cytomegalovirus (CMV) using ELISA. Measurement of CRP by a high-sensitivity CRP assay was done. STATISTICAL ANALYSIS: Multiple logistic regression analysis was used. RESULTS: None of the infectious agents (CMV, H. pylori, C. pneumoniae and HSV-1) showed a significant association with electrocardiogram-defined CAD after adjusting for sex and age. Elevated CRP levels did not show significant association with electrocardiogram-defined CAD independent of seropositivity to one of the four infectious agents, but concurrent elevated CRP levels (>10.0 mg/L) and anti-C. pneumoniae [OR = 1.68 (CI, 1.24-2.59; P=0.04)], H. pylori [OR = 1.98 (CI, 1.26-3.13; P=0.003)], CMV [OR = 1.66 (CI, 1.10-2.49; P=0.01)] or HSV-1 [OR=1.79 (CI, 1.18-2.72; P=0.006)] IgG antibodies were associated with prevalence of electrocardiogram-defined CAD in the general population, after adjustment for multiple risk factors, including age, sex and the components of the metabolic syndrome. CONCLUSIONS: Beyond traditional cardiovascular risk factors, concomitant chronic infection and elevated CRP are significantly correlated with electrocardiogram-defined CAD. PMID- 17337815 TI - Think globally, act locally: expert opinions from Asia on the diagnosis and treatment of pemphigus vulgaris. AB - BACKGROUND: Pemphigus vulgaris (PV) is the most common blistering disease in Iran and many other Asian countries with a relatively high incidence and involvement of both skin and mucous membranes in majority of the patients. AIMS: To assess the opinions of Asian experts on the diagnosis and management of PV. SETTINGS AND DESIGN: It was a questionnaire-based mailed/e-mailed survey. MATERIALS AND METHODS: The questionnaire was sent to 29 dermatologists from different countries of Asia who treat autoimmune blistering disorders, with at least 5 years' experience in this field and who visit at least five new PV patients annually. Questions included duration of experience, number of patients treated and diagnostic and treatment approaches for PV. STATISTICAL ANALYSIS USED: Percentage prevalence; some data are reported as mean +/- SD. RESULTS: All of the 29 physicians participated in the survey; among them, 79.3% visit their patients within 6 months after the onset of symptoms. Diagnosis of PV is confirmed by histologic and direct immunofluorescence examinations by 65.5% of physicians. All of them initiate the treatment with corticosteroids (48.3% with a dose of at least 2 mg/kg/day prednisolone) and 89.7% add adjuvant immunosuppressors at the same time. Of the adjuvant agents used, azathioprine is used by 82.8% of physicians. CONCLUSIONS: Different trends in diagnostic techniques and treatment options for PV among the experienced authorities emphasize the urgent need for large-scale controlled trials in order to reach consensus standards in this field. In addition, regional and worldwide consensus meetings to consider all regional and genetic similarities and differences are highly recommended. PMID- 17337816 TI - Granulocytic sarcoma of breast: an aleukemic presentation. AB - Granulocytic sarcoma is a rare extramedullary tumor composed of immature myeloid cells. It is usually associated with leukemia or other myeloproliferative disorders but can also occur without overt hematologic diseases. The breast is an uncommon site of presentation and requires a high index of suspicion for diagnosis. We report such a case in a 45-year-old female, who presented with nontender left breast lump of 6 months' duration. A peripheral smear and bone marrow examination at that time was normal. A lumpectomy was done. An H and E diagnosis of lobular carcinoma vs. non-Hodgkin's lymphoma was entertained. Immunostains, however, revealed myeloperoxidase, naphthol AS-D chloroacetate esterase and CD43 positivity, indicating a diagnosis of granulocytic sarcoma. It appears that early initiation of systemic AML-type chemotherapy is beneficial and may delay or avert the development of AML in bone marrow and blood. Eight months later, the patient presented with an orbital mass; bone marrow and peripheral smear involvement by AML. PMID- 17337817 TI - Pallido-pyramidal syndrome: a rare entity. PMID- 17337818 TI - Postpartum hemorrhage in two women with impaired coagulation successfully managed with condom catheter tamponade. PMID- 17337819 TI - Febrile seizures: a review for family physicians. AB - Febrile seizures are the most common cause of convulsions in children. Most are simple in nature, although those with focal onset, prolonged duration ((3)15 min) or those that recur within 24 h or within the same febrile illness are considered complex. Diagnosis of this condition is essentially clinical and based on its description provided by parents. Its pathophysiology remains unclear, but genetics plays a major role in conferring susceptibility. Although most febrile seizures are benign and associated with minor viral illnesses, it is critical that the child be evaluated immediately to reduce parental anxiety and to identify the cause of the fever. It is essential to exclude underlying pyogenic meningitis, either clinically or, if any doubt remains, by lumbar puncture. The risk of pyogenic meningitis is as low (< 1.3%) as the risk in a febrile child without seizures. After an initial febrile seizure (simple or complex), 3-12% of children develop epilepsy by adolescence. However, the risk of developing epilepsy after an initial simple febrile seizure is low (1.5-2.4%). Since the vast majority of children have a normal long-term outcome, antiepileptic medication is not recommended to prevent recurrence of febrile seizures. Oral diazepam or clobazam, given only when fever is present, is an effective means of reducing the risk of recurrence. The family physician can play an important role in counseling the parents that most febrile seizures are brief, do not require any specific treatment or extensive work-up, the probability of frequent or possibly threatening recurrences is low and the long-term prognosis is excellent. PMID- 17337820 TI - Jones criteria and underdiagnosis of rheumatic fever. AB - OBJECTIVE: The authors attempt to determine whether typical clinical and laboratory manifestations of acute rheumatic fever (ARF) are in accordance to what has been traditionally described and how useful the Jones criteria are for diagnosis. METHODS: Data from 81 cases of ARF were retrospectively collected. INCLUSION CRITERIA: 5 to 15 years of age and diagnosis of ARF confirmed by 2 or more rheumatologists, sustained for at least 6 months and two or more visits. RESULTS: Girls had more chorea (23/50.0% vs. 5/14.3%)(p< 0.0001). Cardiovascular (65/80.2%) and joint involvements (63 / 77.8%) were the most frequent manifestations. Fever was noted in roughly half of the patients. Arthritis was more frequent than arthralgia (47/58.0% vs. 16/19.8%, respectively) (p< 0.0001); however, no specific pattern of joint involvement was found to be more prevalent. Mitral insufficiency was the most frequently detected echocardiographic sign (53 / 93.0%) and its association with aortic insufficiency was noted in 27 / 47.4% patients. Only 24 / 29.6% patients fulfilled Jones criteria for ARF requiring an evidence of previous group-A streptococcal infection (GASI). When compulsory GASI was disregarded, this number rose to 71/87.7% patients (p< 0.0001). CONCLUSION: Girls were more affected by chorea; heart valves and joints were equally affected and represented the major clinical features; no specific pattern of joint involvement (eg.: migratory arthritis) could be labeled as typical; and strict adherence to Jones criteria, with compulsory documentation of a previous GASI, may lead to underdiagnosis of ARF. PMID- 17337821 TI - Observational sickness assessment by the NICU staff nurses. AB - OBJECTIVE: To see the level of agreement on subjectively assessed sickness by NICU staff nurse with doctor. METHODS: Prospective study in NICU for three months. The nurses were asked to assess whether a baby is sick or not on the basis of observed physical variables. Both the nurses and the attending physician made their assessment on a progress sheet separately. Statistical analysis was carried out to see the agreement of the nurses with the doctors in respect to the sickness assessment, treatment, final outcome and the agreement between the symptoms picked up by the nurses and the doctors. RESULTS: Out of 112 babies admitted, 90 were observed to be sick by the nurses out of which 85 were observed to be sick by the doctors (Kappa=0.4098). Considerable accuracy was noted on comparing symptoms picked up by the nurses and the doctors'. The Kappa value for respiratory, GI and neurological system was 0.4278,0.401 and 0.59 respectively. A significant correlation was seen between the two groups with regard to the treatment given (p value=0.0456). CONCLUSION: Trained NICU staff nurse can identify sick neonate on observation. PMID- 17337822 TI - Helicobacter pylori culture and antimicrobial resistance in Iran. AB - OBJECTIVE: Helicobacter pylori is considered as an important etiologic factor in pathogenesis of peptic ulcer disease, chronic gastritis and gastric cancer. To eradicate this micro-organism, numerous regimens containing various antimicrobial agents have been suggested. However, H pylori antimicrobial resistance is a leading factor to treatment failure and recurrence of the disease. The aim of the study was to evaluate the prevalence of H pylori resistance to metronidazole, clarithromycin, tetracycline, amoxicillin, erythromycin and furazolidone in authors pediatric patients. METHODS: Antral biopsy of all pediatric patients with negative history of receiving anti-H pylori regimen and endoscopic findings of nodular gastritis or peptic ulcer without previous history of NSAID consumption, burning and trauma were performed for H pylori histology, urease test and culture. All positive cultures were tested for antimicrobial susceptibility. RESULTS: Twenty four patients (14 male and 10 female) between 3.5 and 14 years of age were culture positive. 54.16% of the isolates were resistant to metronidazole, 8.33% to amoxicillin, 4.16% to erythromycin and 4.16% to clarithromycin. None of authors patients were resistant to tetracycline and furazolidone. CONCLUSION: H. pylori antimicrobial resistance could be a major contributor to failure of H pylori eradication. Continuous prospective surveillance of H. Pylori is essential. Moreover, culture and antimicrobial susceptibility test is recommended for resistant cases after the first failure to therapy. PMID- 17337823 TI - Immunization in urbanized villages of Delhi. AB - OBJECTIVE: To assess the immunization coverage of BCG, DPT, OPV, Measles, MMR and Hepatitis B vaccines in two urbanized villages of East Delhi and study the factors affecting the coverage. METHODS: Children of age 24-47 months were selected using systematic random sampling. Information on socio-demographic factors and immunization status was obtained by house-to- house visit. Immunization coverage of all vaccines was computed and analysis of association between immunization coverage and socio-demographic factors was done. RESULTS: The coverage levels were 82.7% for BCG, 81.5% for DPT/OPV 1, 76.8% for DPT/OPV 2, 70.7% for DPT/OPV 3 and 65.3% for measles vaccine. It was 41.4% and 41.6% for DPT booster and MMR vaccine. Higher education of mother (OR=1.96) and father (OR=1.80), father's occupation (OR=1.86), residential status (OR=1.76), place of birth (OR=2.64) and presence of immunization card (OR=5.8) were significant determinants for complete immunization on univariate analysis. On regression analysis mother's education (OR=1.43), presence of immunization card OR=2.05 and place of birth (OR=3.80) remained significant. CONCLUSION: Immunization evaluation surveys have shown a wide variation across regions, states and different strata of the society. PMID- 17337824 TI - Iodine status and goiter prevalence after 40 years of salt iodisation in the Kangra District, India. AB - Thirty primary schools were selected in district Kangra utilizing the population proportionate to size cluster sampling methodology in the year 2004. A total of 6939 children were included in the study. The clinical examination of the thyroid of each child was conducted. On the spot casual urine sample and salt samples were collected from a 'sub set of' children included in the study. The Total goiter rate (TGR) was found to be 19.8%. The median Urinary iodine excretion level was 200 microg/l and only 64% of the salt samples had the stipulated level of iodine. The findings of the present study revealed that current iodine status of population is adequate, however, TGR showed mild iodine deficiency (chronic) and there is a need of continued monitoring the quality of iodised salt provided to the beneficiaries under the Universal salt iodisation programme in order to achieve the goal of elimination of Iodine deficiency disorders from district Kangra. PMID- 17337825 TI - Late onset jaundice and urinary tract infection in neonates. AB - OBJECTIVE: To determine the prevalence and the associated parameters of urinary tract infection (UTI) in infants with late onset jaundice. METHODS: This prospective analytic study was conducted among 400 cases, selected by simple sampling from neonates with late onset jaundice admitted in two referral hospitals of Isfahan during a 9-month period. The information including the age, sex and feeding type, as well as the results of physical examination, treatment, radiology studies, etc were recorded. The etiology of jaundice was assessed by laboratory tests. Urine analysis and urine culture were performed for all subjects. XZ and t-test were used for analysis of the data in- SPSS software. RESULTS: Of the 400 icteric neonates, 147 (36.8%) were female and 253 (63.3%) were male; 23 (5.8%) were diagnosed to have UTI, 5 cases (1.3%) had G6PD deficiency, 19 (4.8%) had dysmorphic red blood cell and 3(0.75%) had ABO or RH incompatibility. The relation between the type of feeding, circumcision and UTI was significant (P< 0.05). Of the 23 neonates with UTI,4 cases (17. 39%) were found to have urogenital abnormality. CONCLUSION: UTI was found in 5.8% of infants with late onset jaundice. The study revealed significant association between breast feeding, circumcision and lower prevalence of UTI in icteric neonates. It is suggested that evaluation for UTI should be considered as a screening test in all cases of neonatal late onset jaundice. PMID- 17337826 TI - Radiological assessment of children with pectus excavatum. AB - OBJECTIVE: To assess what degree of chest wall deformation changes statistically reliably after surgery, using pre- and postoperative radiological examination data. METHODS: Radiological chest examinations were performed for 88 children before and after remedial operations. Pre- and postoperative chest radiograph and CT were performed to measure transversal chest width; sagittal left chest side depth, sagittal right chest side depth, sternovertebral distance and vertebral body length. Derivative indices were also estimated: Vertebral index (VI), Frontosagittal index (FI), Haller index (HI) and asymmetry index. Computerized assessment of data was used. For statistical analysis, the software "Statistica 6.0" was used. RESULTS: Postoperatively VI increased approximately by 2.37+/ 2.72, FI decreased by 4.60+/-4.34 and HI value increased approximately up by 0.45+/-0.49. Statistically significant deformation index difference before and after surgery was not detected when VI was below 26.2 (p=0.08), FI was above 32.9 (p=0.079) and HI was less than 3.12 (p=0.098). CONCLUSION: Preoperative CT and X ray assessment of chest wall deformation degree is important for pediatric patients. The following deformation indices are indications for surgical treatment: VI>26, FSI< 33 and HI>3.1. PMID- 17337827 TI - Clinical profile of Saudi children with bronchiectasis. AB - OBJECTIVE: This study represents the experience of a tertiary care center in Saudi Arabia on non-cystic fibrosis bronchiectasis. METHODS: A retrospective review of all patients with confirmed Non-Cystic Fibrosis (Non-CF) bronchiectasis by chest X-ray and or CT chest in a pulmonary clinic for the period 1993-2005 at a tertiary care center in Riyadh. RESULTS: A0 total of 151 cases were diagnosed as Non-CF bronchiectasis. Siventy-five (49.7%) were males, 76(50.3%) were females. One hundred forty-eight (98%) are alive and 3(2%) died. The southwestern regions constituted 72(50%) of the cases. There is a period (5+/- 3.2) years between the start of symptoms and the diagnosis of bronchiectasis. More than 2/3 of the patients had cough, tachypnea, wheezing, sputum production and failure to thrive. Ninety one (60%) had associated disease: Pulmonary diseases in 48(32%), immunodefficiency in 27(18%), CNS in 18(12%), cardiac in 12(8%) and asthma in 103(68%) of the patients. Left lower lobes were commonly involved in 114(76%) cases. Sixty-eight (67%) were found to have sinusitis. Forty-nine (32%) developed gastroesophgeal reflux (GER). Hemophilus influenza was cultured in 56(37%), Strept pneumoniae in 25(17%) and Pseudomonas aeruginosa in 24(16%) of the patients. 80% of the patients who had pulmonary function test had abnormal changes. Disease progression was related to development of symptoms before 5 years of age, persistent atelectasis and right lower lobe involvement (p<0.05). CONCLUSION: Non-CF bronchiectasis is a common problem in Saudi Arabia. Early recognition and institution of treatment with proper vaccination of available anti-bacterial and anti-viral vaccines are encouraged to prevent progression of the disease. PMID- 17337828 TI - Polio eradication in India: the way forward. AB - Despite remarkable decline in the number of poliomyelitis cases, the dream of polio eradication in India remains elusive. This is despite considerable effort and expenditure for well over a decade. Various reasons have been cited for this and interventions implemented accordingly. None of these seem to have borne fruit. It is appropriate to have a relook at the polio eradication strategies in order to learn from past errors and determine a feasible solution to achieve the goal. This article examines important tissues that hamper the eradication effort and proposes a way forward. PMID- 17337829 TI - Evidence based review on levosalbutamol. AB - Salbutamol, the most commonly used bronchodilator, is a chiral drug with R (levosalbutamol) and S-isomers (also known as enantiomer). The commonly used formulation is a racemic mixture that contains equal amounts of both R and S isomers. Levosalbutamol is the therapeutically active isomer and has all the beta 2 agonist activity. Until recently S-salbutamol was considered inert filler in the racemic mixture but animal as well as human studies have shown that S salbutamol is not inert rather it may have some deleterious effects. Enantioselective metabolism of salbutamol leads to higher and sustained plasma levels of S-salbutamol with repeated dosing. There has been concern that chronic use of racemic salbutamol may lead to loss of effectiveness and clinical deterioration. Formulation of salbutamol containing only R- isomer (levosalbutamol) has been available in international market since last few years. Clinical trials in acute as well as chronic asthma in adults as well as children have shown that it has therapeutic advantage over racemic salbutamol and also is more cost effective. But, large multicenter trials are needed to prove its therapeutic superiority and cost-effectiveness in long term. PMID- 17337830 TI - Neonatology in developed and developing nations. AB - Neonatal care has made tremendous improvements in developing countries. However there are number of challenges to be met and neonatal mortality remains unacceptably high. In contrast to this neonatal care in developed nations have moved ahead of a pre-occupation to reducing the neonatal mortality only. The main reasons for this gap are poor infrastructure, resource limitations and lack of systems developed by neonatal units in the developed nations. Though this communication we explore the possibilities of application of health policies in the Australian neonatal units in developing countries. PMID- 17337831 TI - Magnetic resonance imaging of the neonatal brain. AB - Neonatal magnetic resonance (MR) imaging is rapidly becoming the preferred modality for the evaluation of central nervous system disorders in the newborn. Recent literature supports the value of this imaging technique in diagnosing ischemic, hemorrhagic and infectious disease processes in the premature and full term neonatal brain. Recent data in premature newborns with neurological injury also suggest a role for MR imaging in determining long-term neurodevelopmental outcomes. This review article provides a framework and overview on neonatal MR imaging techniques and examines the literature or radiological disease patterns and prognostic implications in common neurological disorders. PMID- 17337833 TI - Congenital malformations of the lung. AB - Congenital malformations of the lung are rare and vary widely in their presentation and severity. The most common manifestation of the congenital cystic disease of the lung at newborn and early infancy is respiratory distress. Later on in life, cysts usually lose this compressive character and may remain asymptomatic until infection occurs, while producing cough, dyspnea and thoracic pain. The purpose of this study is to review authors institutional experience of congenital cystic lung disease, with specific reference to diagnosis, treatment, as well as outcome, furthermore, to present some cases with unusual clinical manifestations. PMID- 17337832 TI - Dysfunction of innate immunity and associated pathology in neonates. AB - The neutrophils and complement system are the critical elements of innate immunity mainly due to participation in the first line of defense against microorganisms by means of phagocytosis, lysis of bacteria and activation of naive B-lymphocytes. In this report we provide an overview of the up to date information regarding the neutrophil and complement system's functional ability in newborn infants in association with the maternal conditions that exist during the intrauterine stage, gestational age and post-neonatal pathology. The neonates' capacity to control the neutrophil and complement protein activation process has also been discussed because of the evidence that uncontrolled activation of these immune elements provides a significant contribution to the tissue damage and subsequent pathology. The authors are confident that despite the many unanswered questions this review updates their knowledge and points the need for further research to clarify the role of the age-associated dysfunction of neutrophils and complement system in the infection and inflammation related pathology of newborn infants. PMID- 17337834 TI - Traumatic pharyngeal pseudodiverticulum mimicking esophageal atresia. AB - Obstruction of passage of a catheter through esophagus in a newborn is mostly diagnosed as esophageal atresia (EA) with or without tracheo esophageal fistula (TEF). Rarely a traumatic instrumentation may produce pharyngeal or upper esophageal perforation and attempt at passage of a catheter may produce a false passage submucosally called pseudodiverticulum. Here it is present the case of a extremely premature (28 wk) and low birth weight (950 gms) newborn with traumatic laceration and pharyngeal pseudodiverticulum mimicking EA. The authors discuss the diagnostic characteristics and management of such a situation. PMID- 17337835 TI - Paratyphoid sepsis. AB - A large for gestational age male baby was born to a healthy young primigravida, on L-thyroxime, at 40 weeks by caesarean delivery in a tertiary care hospital. The baby had episodes of hypoglycemia during his immediate four postnatal days in the nursery that were successfully managed with intravenous glucose administration. The baby became unwell on day 5 and had a positive sepsis screening test. Blood culture revealed a multidrug susceptible S. Paratyphi A strain, which he probably acquired on the first or second postnatal day from the contaminated expressed breast milk or the formula feed. PMID- 17337836 TI - Autosomal recessive type I lissencephaly. AB - Lissencephaly (LIS) is a brain malformation manifested by a smooth cerebral surface, thickened cortical mantle and microscopic evidence of incomplete neuronal migration, excluding polymicrogyria and other cortical dysplasias. It is important to consider LIS in the diagnosis of developmental delay as many patients may be diagnosed as cerebral palsy. It may have familial occurrence and can occur in sibs of same family often leading to a diagnostic problem. Several lissencephaly syndromes have been described. Here a familial syndrome of lissencephaly is reported. Autosomal recessive inheritance is suggested by recurrence in sibs within the same family, but germ cell mosaicism for a dominant mutation cannot be excluded. PMID- 17337837 TI - Eventration of the diaphragm and associations. AB - Eventration of the diaphragm, most often an isolated entity and detected incidentally, has been known to be associated with several genetic syndromes. Authors report their experience of seeing diaphragmatic eventration in association with Poland syndrome and wandering spleen syndrome and briefly discuss the literature. PMID- 17337838 TI - Infantile meningitis due to Salmonella enteritidis. PMID- 17337839 TI - Immature mesenteric teratoma causing intestinal obstruction. PMID- 17337840 TI - Cardiac involvement determines the prognosis of Duchenne muscular dystrophy. PMID- 17337841 TI - [Dietary habits and disease patterns in the Japanese elderly]. PMID- 17337842 TI - [Molecular mechanisms of atherogenesis associated with aging]. PMID- 17337843 TI - [Application of neuroleptics for dementia]. PMID- 17337844 TI - [Guidelines for medical treatment and its safety in the elderly]. PMID- 17337845 TI - [Hypertensive heart disease and sleep apnea syndrome in the elderly]. PMID- 17337846 TI - [Percutaneous coronary intervention for the elderly patients]. PMID- 17337847 TI - [From Japanese Conference of Geriatric Gastroenterology]. PMID- 17337848 TI - [Geriatric medicine in the field of urology]. PMID- 17337849 TI - [Topics on gerontology nursing]. PMID- 17337850 TI - [Japan Society of Geriatric Anesthesia]. PMID- 17337851 TI - [Japan Geriatric Neurosurgery Society]. PMID- 17337852 TI - [Medical care for the elderly in rural areas]. PMID- 17337853 TI - [Personalized (tailor-made) medicine]. PMID- 17337854 TI - [Therapeutic angiogenesis by bone marrow mononuclear cell transplantation: limitation in the elderly and augmentation by angiopoietin 1 gene therapy]. PMID- 17337855 TI - [Regenerative medicine of bone and cartilage]. PMID- 17337856 TI - [Neurological disorders and neural regeneration: special reference to Parkinson's disease and cerebral ischemia]. PMID- 17337857 TI - [Regeneration medicine for the inner ear]. PMID- 17337858 TI - [Possibility of alveolar regeneration]. PMID- 17337859 TI - [Prevalence and characteristics of urinary incontinence in community-dwelling elderly as determined by comprehensive health examination and interview for the prevention of geriatric syndrome and bed-ridden state]. AB - AIM: We examined the prevalence and characteristics of urinary incontinence in community-dwelling elderly individuals. METHODS: The participants were 1,783 individuals (768 men and 1,015 women) aged over 70 years who participated in a comprehensive health examination involving a medical examination and interview, plus physical performance tests. Differences in characteristics between individuals with and without urinary incontinence were examined, and multivariate logistic regression models were used to describe the characteristics associated with urinary incontinence. RESULTS: The prevalence of urinary incontinence was 13.4% in men and 23.3% in women. Urinary incontinence was significantly associated with a lower level of physical fitness. Multivariate logistic regression showed that urinary incontinence was significantly associated with a slower walking speed (Odds Ratio (OR) = 0.19, 95% Confidence Intervals (CI) 0.08 0.48) and lower serum albumin level (OR = 0.40, 95% CI 0.16-0.99) in men, and with a slower walking speed (OR = 0.29, 95% CI 0.15-0.56), a higher BMI (OR = 1.09, 95% CI 1.04-1.14), depression (OR = 3.06, 95% CI 1.40-6.69), and lack of physical activity (OR = 0.70, 95% CI 0.50-0.98) in women. CONCLUSION: The characteristics of urinary incontinence in this cohort of community-dwelling elderly individuals were a low level of physical fitness and poor nutritional state in men, and a low level of physical fitness, a tendency to be obese, a poor mental health state, and lack of physical activity in women. PMID- 17337860 TI - [Creatinine clearance estimation in the extremely elderly subjects]. AB - BACKGROUND: It has been reported that elderly outpatients take at least 6 different kinds of medication. PURPOSE: To know which formula will best predict creatinine clearance, because 24-hour urine collection is difficult for elderly outpatients. PATIENTS AND METHODS: We compared four types of formulae (Cockcroft and Gault, Yasuda, Orita, Walser) to estimate creatinine clearance using serum creatinine of 143 elderly inpatients (73 men, 70 women, mean age 82.9 +/- 8.6 years old) including 67 extremely elderly people with various underlying diseases. RESULT: The formula of Cockcroft and Gault showed the best correlation with creatinine clearance in the extremely elderly subjects (r = 0.74) as well as in people under 85 years (r = 0.76). However, the estimated values of the extremely elderly women were lower than actual creatinine clearance. CONCLUSION: The formula of Cockcroft and Gault is the best predictive equation of creatinine clearance, except in the extremely elderly women. PMID- 17337861 TI - [Relationship between eating dysfunction and life span and mortality in institutionalized elderly people]. AB - AIM: The aim of this study was to evaluate the relationship between eating disorders and anticipated life span stage and mortality in institutionalized elderly people. METHODS: Ninety-eight elderly residents (mean 86.3 +/- 5.9 years) at a nursing home were selected for investigation of the date and cause of death. Inclusion was limited to those who died within one week from admission to the institution/hospital. Data on 11 potential prognostic factors were analyzed: underlying disease, activity of daily living (ADL), disorder of anticipatory stage, swallowing function, need for feeding assistance, weight decrease rate in the part 6 months, body mass index (BMI), minimum nutritional assessment (MNA), occlusal status, age and sex. These 11 factors were analyzed by Kaplan-Meier survival curve, and either the log-rank or Wilcoxon test was used to analyze significant differences in survival days in subjects with and without the factors listed above. Moreover, the regression analysis was made using Cox proportional hazards model, a nonlinear multivariate analysis, to extract factors contributing greatly to short survival days. RESULTS: The survival days showed significant differences in six factors; ADL, disorder of anticipatory stage, swallowing function, need for feeding assistance, BMI and MNA. Three factors were shown to be related to a significantly shorter mortality by the Cox proportional-hazards model: disorder of anticipatory stage (hazard rate = 2.85, 95% CI = 1.04-7.83), swallowing function (hazard rate = 2.90, 95% CI = 1.06-7.91) and BMI (hazard rate = 2.54, 95% CI = 1.00-6.44) were involved in. CONCLUSION: This study speculated that an appropriate response with a focus on feeding training may possibly contribute to prolong the mortality of elderly people. PMID- 17337862 TI - [Attitudes of Japanese general practitioners towards referrals of patients with dementia]. AB - AIM AND METHODS: The cooperation of general practitioners and specialists is crucial to establish comprehensive medical services for demented older adults. In the current study we conducted a survey regarding the attitudes towards referrals between general practitioners and specialists by sending a questionnaire to 1,176 general practitioners. RESULTS: The 39.1% of the general practitioners returned the questionnaire. Of the respondents, 68.8% answered that they did not want referrals of demented patients from specialists, however, when analysis was limited to those who had an internal medicine background, only 26.3% did not want referrals. Difference of subspecialties within internists did not affect the preference for referrals. Regarding the reasons for referring the demented patients to specialists, more than 70% of the general practitioners chose "accurate diagnosis of the cause of dementia" and "decision of therapeutic plans". CONCLUSION: The majority of general practitioners in Japan may still be reluctant to follow patients with dementia mainly because they regard the practice of seeing demented patients as the subject outside of their specialty. Therefore providing general practitioners with opportunities to receive training programs regarding the practice and care of demented patients, as well as establishing support from specialists is necessary. PMID- 17337863 TI - [Prospective study of the relation between exercise performance for health promotion, self-efficacy, and outcome expectation of elderly people]. AB - AIM: Self-efficacy and outcome expectation are psychological factors influencing performance behavior. Self-efficacy is a person's confidence that one can successfully perform the behavior to produce depend outcomes. Outcome expectation is the estimate that a favorable consequence will be produced by the behavior. These psychological factors are important reasons to perform exercise for health promotion among elderly people, but little is known about the relations among them. Therefor this study examined the relation among exercise for health promotion, self-efficacy, and outcome expectation of elderly people. METHODS: This was a prospective study using self answered questionnaire. Data were collected from before and three follow-up investigations at 3 months intervals over a 9 month period. The sample was composed of 43 elderly people who applied for exercise program. RESULTS: A strong correlation (r = 0.375 - r = 0.412) was observed between self-efficacy and exercise performance after three months. There was a strong correlation (r = 0.349 - r = 0.665) between outcome expectation and exercise performance at 3 months, 6 months, and 9 months. CONCLUSION: These findings suggest that self-efficacy and outcome expectation are significant predictors of exercise performance for health promotion in elderly people. PMID- 17337864 TI - [Elderly case of isolated ACTH deficiency presenting with depression and digestive symptoms]. AB - A 76-year-old man was first referred to his local hospital at the beginning of August 2005 with nausea and vomiting, and was admitted on August 15 with progressive fatigue of unknown etiology. Gastrointestinal examination was performed, but no obvious abnormalities were detected in the upper or lower digestive tract. Hematology tests also revealed no abnormalities, except for slight eosinophilia. He developed depression and was given an antidepressant agent. After suffering from hyponatremia and disorientation, he was subsequently admitted to our hospital on August 28. At that time, serum adrenocorticotropic hormone (ACTH) and cortisol levels were low, while both the ACTH and corticotrophin-releasing hormone (CRH) stress tests showed no response. Other stress tests revealed normal responses, so he was given a diagnosis isolated ACTH deficiency and received corticosteroid therapy. In summary, we report an elderly case of isolated ACTH deficiency with nonspecific initial manifestations such as nausea, fatigue, and depression. PMID- 17337866 TI - The 16th Tokai Regional Meeting of The Japan Geriatrics Society. PMID- 17337865 TI - [Case of rectal carcinoma discovered after extracting a single brain metastasis]. AB - A 79-year-old woman had shown a decline of volition nine months before admission. Because she demonstrated a depressive state, she had been treated with an antidepressant for one month before admission. Thereafter, she became incontinent and showed a poor appetite since two days before admission. Plain computed tomography scan showed an extensive low density area in the right frontal lobe. Cerebral magnetic resonance imaging revealed a tumor with edema (3 cm in diameter), which showed heterogeneous enhancement. The solitary tumor was removed by craniotomy. Metastatic carcinoma was suspected on histological examination, but the primary cancer was not able to be detected by a whole body examination, except for colonoscopy, which was refused by her family. She demonstrated intestinal bleeding about five months after the craniotomy. Rectal cancer was discovered by colonoscopy and she underwent Hartman's procedure. Histological examination revealed poorly differentiated adenocarcinoma similar to resected brain tumor. The final solitary diagnosis was metastatic carcinoma from primary rectal cancer. Solitary brain metastasis from colon cancer is extremely rare, however, we should consider the possibility in cancers of the digestive tract. PMID- 17337867 TI - The 17th Hokkaido Regional Meeting of The Japan Geriatrics Society. PMID- 17337868 TI - The 17th Tohoku Regional Meeting of The Japan Geriatrics Society. PMID- 17337869 TI - [An increase in body weight after eradication of Helicobacter pylori]. PMID- 17337870 TI - [Diagnosis of hepatic encephalopathy]. PMID- 17337871 TI - [Treatment strategy for hepatic encephalopathy]. PMID- 17337872 TI - [Effect of clinical pathway in the treatment of inpatients with ischemic colitis]. AB - Based on the results of a retrospective review of clinical data on inpatients with ischemic colitis treated at our hospital, we created a clinical pathway and evaluated its usefulness. We used the clinical pathway for 21 inpatients, and the patient who fulfilled the criteria consisted of 18 inpatients. The fasting period after the onset and the duration of hospitalization were compared with those of 60 patients before implementation of the clinical pathway. The fasting period after the onset before and after implementation were 6.20+/- 3.42 days (mean+/- SD), and 5.28+/- 1.27 days, respectively. The duration of hospitalization before and after implementation was 10.37+/- 7.32 days, 8.37+/- 2.89 days, respectively. The clinical pathway is useful for shortening the duration of hospitalization, enhancing the uniformity of treatment and controlling the treatment risk. PMID- 17337873 TI - [Occurrence and prognosis of hepatocellular carcinoma]. AB - Tomiura, a rural area of Chiba Prefecture in which community-based HCV screening has been carried out since 1991, is known as a high-incidence area of HCV. This study was conducted to clarify the clinical characteristics of subjects with positive HCV antibody titer found on mass survey, in relation to the development and outcome of hepatocellular carcinoma. We analyzed clinical data of patients with positive HCV antibody test results followed up for 9 to 11 years after the mass survey examinations. Among 171 patients, we identified 23 cases (13.5%) of hepatocellular carcinoma in a 9-year period. Correlations have been identified between the occurrence of hepatocellular carcinoma and those factors including gender, aminotranseferase levels, platelet count and ultrasound findings at the time of the first health screening, as well as patterns of fluctuation in aminotranseferase levels during the follow-up period. Among those patients with hepatocellular carcinoma, 11 patients survived for more than 5 years. The survival period has been found to be related to AST level at the time of first health screening, the findings in ultrasound scanning when the carcinoma was initially identified, and patterns of fluctuation in aminotranseferase levels subsequent to the first diagnosis. PMID- 17337874 TI - [The role of multi-detector-row computed tomograph in the diagnosis of intraductal papillary-mucinous tumors of the pancreas in comparison to endoscopic retrograde pancreatography, endoscopic ultrasonography, magnetic resonance cholangiopancreatography]. AB - Thirty patients with intraductal papillary-mucinous tumor (IPMT) of the pancreas underwent multidetector-row CT (MD-CT) in addition to endoscopic retrograde pancreatography (ERP), and, in 27 cases magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS). The usefulness of MD-CT was investigated by comparing various imaging methods of the communication from the main pancreatic duct (MPD) to patulous/bulging papilla in addition to the indices for benign or malignant disease, the degree of dilation of the MPD, localization and size of cystic lesions, and presence or absence of neoplastic lesions, such as thickened walls and septa, intramural nodule, solid mass. With MD-CT, dilation of the MPD and localization and size of cystic lesions were accurately assessed, even in patients with obstruction of the main pancreatic duct in whom ERP was difficult to perform regardless of the presence or absence of massive amount of mucus. MD-CT with reconstructive imaging, such as MPR imaging and CPR imaging, allowed us to assess communication with the MPD and patulous/bulging papilla easier than MRCP. In our study, MD-CT was useful in the evaluation of thickened walls and septa that are predictive factors of malignancy in IPMT. PMID- 17337875 TI - [A case of widespread ileal stenosis caused by metastatic disseminated peritoneal carcinomatosis from lung cancer resected 8 years previously]. AB - A 46-year-old man was admitted because of ileus. He had undergone an operation for lung carcinoma (stage IA) 8 years previously in another hospital. Because small bowel enema study showed widespread stricture of the ileum, we performed an operation. During the operation we diagnosed metastatic small bowel carcinoma. Because the resected sample of the small bowel carcinoma was similar to the lung carcinoma pathologically and detailed examination after the operation showed no other neoplasm, we considered this case to be small bowel metastasis of the lung carcinoma resected 8 years previously. PMID- 17337876 TI - [Two cases of primary T cell lymphoma of the small intestine diagnosed by perforated peritonitis]. AB - We encountered 2 cases (a 28-year-old man and a 63-year-old woman) of primary T cell lymphoma of the small intestine diagnosed by perforated peritonitis. T cell lymphoma perforates the small intestine more easily than B cell lymphoma, because T cell lymphoma infiltrates the intestinal tract wall, and forms an ulcerative tumor. PMID- 17337877 TI - [A case of primary carcinoma of the cystic duct with limy bile]. AB - A 78-year-old man had been admitted to a previous hospital because of epigastralgia and a diagnosis of cholecystolithiasis had been made. He had been transferred to our institution for further examination. CT scan and US revealed chronic cholecystitis and gallstone, however, ERC revealed severe obstruction of the cystic duct and EUS revealed dilation of that duct and a solitary mass there. Carcinoma of the cystic duct was diagnosed, and we performed cholecystectomy and resection of the extrahepatic duct with two-field lymphadenectomy. The pathological specimen showed a round flat elevated mass localized in the cystic duct. Histopathologically, the diagnosis was well differentiated tubular adenocarcinoma of the cystic duct with limy bile and tiny gallstone. PMID- 17337878 TI - [A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy]. AB - Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive. PMID- 17337879 TI - [A case of splenic inflammatory pseudotumor]. AB - A 59-year-old man was admitted to our hospital because of continuous C-reactive protein elevation. Abdominal computed tomography scan revealed a low density mass on the surface of the spleen. Magnetic resonance imaging showed low intensity at peripheral area and slightly high intensity in the central area of the mass lesion on T1 and T2-weighted image. Splenectomy was performed since we could not rule out the possibility of malignant neoplasm only by diagnostic imaging. The pathological diagnosis of the tumor was inflammatory pseudotumor. Splenectomy is considered to be significant from the standpoints of both diagnosis and therapy in cases in which diagnostic imaging is difficult to interpret. PMID- 17337880 TI - Stem cells in the postnatal pituitary? AB - Tissue-specific stem cells are uncovered in a growing number of organs by their molecular expression profile and their potential for self-renewal, multipotent differentiation and tissue regeneration. Whether the pituitary gland also contains a pool of versatile 'master' cells that drive homeostatic, plastic and regenerative cell ontogenesis is at present unknown. Here, I will give an overview of data that may lend support to the existence of stem cells in the postnatal pituitary. During the many decades of pituitary research, various approaches have been used to hunt for the pituitary stem cells. Transplantation and regeneration studies advanced chromophobes as possible source of new hormonal cells. Clonogenicity approaches identified pituitary cells that clonally expand to floating spheres, or to colonies in adherent cell cultures. Behavioural characteristics and changes of marginal, follicular and folliculostellate cells during defined developmental and (patho-)physiological conditions have been interpreted as indicative of a stem cell role. Expression of potential stem cell markers like nestin, as well as topographical localization in the marginal zone around the cleft has also been considered to designate pituitary stem cells. Finally, a 'side population' was recently identified in the postnatal pituitary which in many other tissues represents a stem cell-enriched fraction. Taken together, in the course of the long-standing study of the pituitary, several arguments have been presented to support the existence of stem cells, and multiple cell types have been placed in the spotlight as possible candidates. However, none of these cells has until now unequivocally been shown to meet all quintessential characteristics of stem cells. PMID- 17337881 TI - Automatic pressure titration with APAP is as effective as manual titration with CPAP in patients with obstructive sleep apnea. AB - BACKGROUND: The optimal approach to initiate positive-pressure therapy in patients with obstructive sleep apnea is still debated. Current options are autotitrating positive airway pressure (APAP) or manual titration with continuous positive airway pressure (CPAP). Procedures differ by parameters and by algorithms used for adapting pressure. OBJECTIVES: To evaluate the efficacy of attended automatic titration in a randomized crossover study compared with manual titration over 2 nights where the sequence of the titration mode was changed. Therapy outcome was controlled after 6 weeks. METHODS: 21 sleep apnea patients were treated using manual CPAP versus automatic APAP titration. The mode used during the 2nd night was continued for 6 weeks. Cardiorespiratory polysomnography, Epworth Sleepiness Scale (ESS), SF-36 score and compliance were assessed. RESULTS: Apnea-hypopnea index reduction was equally effective at similar effective pressure independent of the titration mode. If APAP was applied during the 1st night, total sleep time was longer (384 vs. 331 min, p < 0.01) and sleep efficacy was higher (91 vs. 81%, p < 0.01) than after starting with manual titration with CPAP. Compliance was comparable in both groups (4.6 +/- 1.9 h). The ESS improved in both groups (from 12.9 to 6.5). SF-36 scores and therapeutic pressure did not much change. CONCLUSIONS: Taking the sequence of titration into account, we found equal effectiveness of CPAP and APAP. Sleep quality was better with initial application of APAP - which favors attended automatic titration if only 1 titration night is possible. Both modes are comparable after 6 weeks regarding therapeutic pressure, efficacy, compliance and quality of life. PMID- 17337882 TI - Sonographic diagnosis and follow-up of pneumonia: a prospective study. AB - BACKGROUND: Although transthoracic ultrasound offers several important advantages as diagnostic imaging technique in pleural and pulmonary conditions, its significance for the diagnosis and monitoring of pneumonia has yet to be established. OBJECTIVES: To identify sonographic features associated with pneumonia at admission and during the course of the disease under treatment. METHODS: Thirty patients (12 females, 18 males; median age 65.5 years) with X-ray proven pneumonia underwent transthoracic sonography (TS) on day 0, between days 1 and 3, 4 and 7, 8 and 14, 15 and 21, and after day 21. TS was assessed according to: number, location, shape, echogenicity, echotexture, echostructure, breath depending movement, size of pneumonic lesions, bronchoaerogram, fluid bronchogram, superficial fluid alveologram, necrotic areas, vascularity and incidence of local and/or basal pleural effusion. RESULTS: Thirty-three pneumonic infiltrates were eligible for analysis in 30 patients. In 57% (17/30), the likely pathogenic microorganism was identified. Pneumonia was recognized as a hypoechoic area of varying size (mean size between 33.7 x 9.38 and 91.2 x 45.3 mm) and shape, with irregular and blurred margins along with a nonhomogeneous echotexture. The most characteristic feature was a positive bronchoaerogram (32/33). Sixty-one percent (20/33) revealed basal and 9% (3/33) local effusion. During follow-up, lesions decreased in size or disappeared (30/33) or decreased in number (4/9). The bronchoaerogram became less pronounced (13/32), basal pleural effusion either diminished (7/20) or dissipated (7/20), as did localized effusion (3/3). In 30 cases, the course of pneumonia was comparable using X-ray and TS. CONCLUSIONS: TS is a noninvasive technique for the diagnosis and follow up of patients with pneumonia. PMID- 17337883 TI - Pituitary action of cytokines: focus on BMP-4 and gp130 family. AB - The anterior pituitary can develop benign tumors of different sizes, classified as micro- and macroadenomas, frequently associated with high levels of hormone production, leading to different associated syndromes like Cushing's disease, acromegaly or prolactinomas. Much work has been done in order to understand the signaling pathways and the factors and hormones involved in the pituitary tumorigenic process. In recent years, much evidence has been collected and it is now well documented that cytokines of the gp130 family, such as interleukin-6, that use gp130 as a common signaling protein stimulate not only the proliferation but also the hormone secretion of pituitary cells. Experiments in vivo have shown that the overexpression of the gp130 receptor resulted in pituitary abnormal growth. Moreover, it has been recently described that bone morphogenetic protein 4 (BMP-4), a member of the TGF-beta family, has a stimulatory role on lactosomatotropic cells promoting the development of prolactinomas but it has an inhibitory action on the corticotropic lineage. This inhibitory action prevents Cushing's disease progression. Furthermore, BMP-4 mediates the antiproliferative action of retinoic acid in these cells. The present review highlights the most recent work about gp130 and TGF-beta cytokine families and their role in pituitary tumorigenesis. PMID- 17337884 TI - Hormonal signaling and pituitary adenomas. AB - In recent years the demonstration that human pituitary adenomas are monoclonal in origin provides further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. Mutations in common oncogenes and tumor suppressor genes are only exceptionally involved in pituitary tumors. Since pituicytes may proliferate in response to hypothalamic neurohormones, locally produced growth factors and peripheral hormones, it has been speculated that dysregulation of the signaling molecules that constitute these pathways may confer growth advantage to the target cell, finally resulting in tumor formation. The only mutational change so far recognized to be unequivocally associated with pituitary tumors occur in the Gs alpha gene (GNAS1) and cause constitutive activation of the cAMP-dependent pathway. However, other components of pituitary-specific pathways are frequently altered in their expression and activity. This review will focus on the possible impact of G proteins and other components of hormone signaling on pituitary tumorigenesis. PMID- 17337885 TI - Long-term efficacy of tonsillectomy in Chinese patients with IgA nephropathy. AB - BACKGROUND: To investigate the clinical efficacy of tonsillectomy on long-term clinical remission and renal survival of immunoglobulin A nephropathy (IgAN) patients in China. METHODS: We performed a 130-month retrospective case-control study of 112 patients with idiopathic biopsy-diagnosed IgAN from 1983 to 1999. Fifty-four patients underwent tonsillectomy and 58 patients did not. The clinical remission rate during follow-up and variables to predict clinical remission were estimated by chi2 test and multivariate Cox regression analysis; renal survival was evaluated by Kaplan-Meier analysis. RESULTS: Up to 2006, the follow-up period lasted 130 +/- 50.3 months (60-276 months). The clinical remission rate was 46.3% in patients with tonsillectomy and 27.6% in those without tonsillectomy during follow-up. Multivariate analysis demonstrated that tonsillectomy was not an independent impact factor for renal clinical remission (p = 0.386). By Kaplan Meier analysis, there was no significant difference in renal survival rate between patients with tonsillectomy and those without tonsillectomy (p = 0.059). CONCLUSION: The clinical remission rate in IgAN patients with tonsillectomy was higher than that in patients without tonsillectomy during follow-up. But within 130 months, it was difficult to find statistical difference in renal survival between IgAN patients with and without tonsillectomy. PMID- 17337886 TI - Associations between the CYBA 242C/T and the MPO -463G/A polymorphisms, oxidative stress and cardiovascular disease in chronic kidney disease patients. AB - Genetic variations in the NADPH/MPO system in chronic kidney disease (CKD) patients might lead to altered activity of these enzymes, and thus to altered risk for oxidative stress (OS) and cardiovascular disease (CVD). We evaluated the impact of 242C/T CYBA and -463G/A MPO polymorphisms on OS and CVD mortality in stage 5 CKD patients starting dialysis. Two hundred and fifty-seven patients were genotyped using Pyrosequencing. Plasmalogen [dimethylacetal (DMA) 16/C16:0] was used as OS marker. CVD was assessed from patient history and clinical symptoms. Prevalence of CVD was higher (35%) in GG patients (MPO) compared to AG (26%) and AA (0%) patients (p < 0.01). Patients with CC genotype (CYBA) had lower levels of DMA 16/C16:0 (ratio 0.071 +/- 0.003) compared to TT patients (0.089 +/- 0.006; p < 0.05). These patients also had increased CVD mortality compared to CT and TT patients (chi(2) 2.19; p < 0.05). We conclude that genetic variations in the NADPH/MPO system are associated with OS, presence of CVD and CVD-related mortality in CKD patients. PMID- 17337887 TI - Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Effectively Avoiding Second Strokes Trial (PRoFESS). AB - BACKGROUND: Individuals with transient ischemic attack and ischemic stroke have a high risk of recurrent stroke and death. While acetylsalicylic acid (ASA, aspirin) is proven and accepted as standard therapy in these patients, recent trials demonstrate that a combination of ASA and dipyridamole (DP) or clopidogrel may be superior to ASA. Blocking the renin-angiotensin system with angiotensin converting enzyme inhibitors or angiotensin receptor blockers may also reduce recurrent stroke. The ongoing PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial is designed to evaluate whether ASA + extended release DP compared to clopidogrel, and whether telmisartan in addition to usual care in individuals after a stroke, will reduce the risk of further strokes. METHODS: PRoFESS is a multicenter, randomized, double-blind trial involving 695 sites from 35 countries or regions. Patients > or = 50 years presenting with an ischemic stroke < 120 days who were stable were randomized. The primary outcome for the trial is recurrent stroke, using a time-to-event analysis. The most important secondary outcome is the composite of stroke, myocardial infarction or vascular death. Other secondary outcomes include this composite + congestive heart failure, new-onset diabetes, other designated occlusive vascular events (pulmonary embolism, deep-vein thrombosis, peripheral arterial occlusion, transient ischemic attack, cerebral venous thrombosis or retinal vascular accident not classified as stroke), any death, stroke subtype by TOAST criteria and Mini Mental State Examination score. Safety is evaluated by assessing the risk of major hemorrhagic events. The comparison between ASA + DP and clopidogrel is based on an initial assessment of noninferiority, followed by evaluation of superiority, while for telmisartan, we will assess its superiority over placebo. RESULTS: With over 20,000 patients randomized, and utilizing a 2 x 2 factorial design, PRoFESS is the largest stroke trial to investigate the prevention of recurrent stroke. The mean age was 66.1 +/- 8.6 years, and 36.0% of the patients were females. The median time from qualifying event to randomization was 15 days with 39.9% of patients randomized within 10 days. According to the TOAST criteria, 28.5% of the strokes were due to large-vessel disease, 52.1% to small vessel disease, 1.8% to cardioembolism, and 2.0% to other determined etiologies and 15.5% were of undetermined etiology. CONCLUSIONS: PRoFESS is the largest secondary stroke prevention trial to date and will directly compare two antiplatelet regimens as well as the benefit of telmisartan versus placebo. PMID- 17337888 TI - Effect of melatonin on healing of colonic anastomosis in a rat model of peritonitis. AB - BACKGROUND: The aim of this study is to determine the effect of melatonin on intestinal anastomosis in the presence of peritonitis. MATERIAL AND METHODS: 32 Wistar albino rats were randomized into four groups (n = 8): A (sham), B (control), C (melatonin 5 mg/kg), and D (melatonin 10 mg/kg). In group A, only cecal dissection was carried out. In the other groups, cecal ligation and puncture (CLP) followed cecal dissection in order to induce bacterial peritonitis. 24 h after the previous operation, cecal resection and ileocolic anastomosis were performed in the rats of all groups. In group C (5 mg/kg) and group D (10 mg/kg), melatonin was injected for 5 consecutive days starting after CLP. At the 48th hour of the CLP procedure, blood was drawn via the tail vein for tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) analysis, and on the 4th day of the experiment relaparotomy was carried out for bursting pressure (BP) measurements. The intestinal tissue containing the anastomotic line was then snap-frozen in liquid nitrogen and stored at -80 degrees C for determination of tissue levels of malondialdehyde (MDA) and glutathione (GSH). RESULTS: The tissue MDA level, blood TNF-alpha and IL-6 levels of group B were significantly higher than in the other groups, whereas the BP results and GSH levels of group B were found to be significantly lower than in the other groups. The results of groups C and D are statistically different from those of group B. When we compared the results of groups C and D, we found significantly higher results in terms of BP and GSH levels in group D and also significantly lower results in terms of MDA, blood TNF-alpha and IL-6 levels in group D. CONCLUSION: The findings of this experiment suggest that melatonin has a dose-independent positive effect on wound healing of colonic anastomosis. PMID- 17337889 TI - Instillation of taurolidine/heparin after laparotomy reduces intraperitoneal tumour growth in a colon cancer rat model. AB - OBJECTIVE: To investigate whether irrigation of the abdominal cavity after laparotomy for caecum resection with taurolidine/heparin or adhesion prophylactic substances reduces intraperitoneal tumour growth or the local recurrence rate in a colon carcinoma rat model. METHODS: 60 BDIX rats underwent caecum resection after intraperitoneal inoculation of 1 x 10(4) colon carcinoma cells (DHD/K12/TRb). Intergel, Interceed, taurolidine/heparin or NaCl 0.9% were intraperitoneally applied after randomisation. Finally, the total number and total weight of intraperitoneal metastases were determined as well as the adhesion score according to Moreno. Metastatic tissue was examined histologically and immunohistochemically (E-cadherin, CD44, beta(1)-integrin). RESULTS: Taurolidine/heparin significantly reduced not only the total number (3 vs. 11 in the control group) but also the total weight (65 vs. 330 mg) of intraperitoneal metastases in comparison to the control group (p = 0.003 and p = 0.005). E Cadherin expression in the metastatic tissue of animals treated with taurolidine/heparin was significantly decreased (p = 0.016). CONCLUSION: Taurolidine/heparin effectively reduces intraperitoneal tumour growth when used as an intraoperative lavage. These results represent a good rationale for intraoperative adjuvant irrigation with taurolidine/heparin during resection of colon cancer. PMID- 17337890 TI - Correlation between the serum values of soluble intercellular adhesion molecule-1 and total sialic acid levels in patients with breast cancer. AB - BACKGROUND: In this study, we aimed to investigate serum total sialic acid (TSA) and soluble intracellular adhesion molecule-1 (sICAM-1) levels in breast cancer patients to find a correlation with the cancer stage. METHODS: The parameters from sera of 61 patients with breast cancer were measured. The concentrations of serum sICAM-1 and TSA were measured in serum samples from 61 patients with breast cancer and 25 healthy control subjects using enzyme-linked immunoassay and thiobarbituric acid method. RESULTS: Mean serum sICAM-1 and TSA levels were significantly higher in the total patient group than in the control group (p < 0.001). Thus, the correlation between TSA and sICAM-1 became more significant in metastatic breast cancer. There were significant positive correlations between TSA and sICAM-1 in stage I+II (r = 0.59, p < 0.05), stage III (r = 0.47, p < 0.05), and stage IV (r = 0.89, p < 0.01), and total patient group (r = 0.56, p < 0.001). CONCLUSION: SerumsICAM-1 and TSA levels were higher in patients with breast cancer, than that of the control group, and also in the metastatic breast cancer group. Significant correlations between serum sICAM-1 and TSA may reflect the similar function of these molecules as adhesion molecules, and their roles in the carcinogenesis of breast cancer as well as metastasis. PMID- 17337891 TI - Effects of two conventional preoperative radiation schedules on anastomotic healing in the rat colon. AB - BACKGROUND: Preoperative radiotherapy (RT) is an increasingly popular form of adjunct therapy for rectal cancer; however, little is known about its effects on matrix metalloproteinase (MMP) expression in colonic anastomotic healing. METHODS: Wistar rats were irradiated to a total dose of 25 or 40 Gy. Four days after the end of RT, an end-to-end colorectal anastomosis was performed. Animals were sacrificed at 1, 3, and 7 days after the anastomosis. A control group was studied similarly, but was not irradiated. RESULTS: No significant differences were found in peritonitis rate and anastomotic complications. The average bursting pressure and breaking strength were only reduced significantly in the rats irradiated with 40 Gy. However, the concentration and the content of hydroxyproline in anastomotic tissues were unchanged. In irradiated rats, MMP-2 and MMP-9 were significantly increased at 40 Gy, but not at 25 Gy. On the other hand, 25-Gy irradiation induced a smaller increase in the levels of the tissue inhibitors of metalloproteinase-1 compared with the controls. CONCLUSION: Anastomotic strength is adversely affected by high-dose fractionated preoperative RT. In contrast, preoperative RT at 25 Gy in five fractions over 5 days is safe with regard to the maintenance of wound strength in colorectal anastomosis. PMID- 17337892 TI - Doppler study of splanchnic hemodynamics in Hirschsprung's disease. AB - BACKGROUND: Doppler studies of splanchnic vessels have demonstrated alteration in blood flow in bowel obstruction and strangulation. The aim of this study was to evaluate hemodynamic changes in celiac artery (CA), superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) using pulsed Doppler sonography (PDS) in Hirschsprung's disease. MATERIAL AND METHODS: Fasting splanchnic flowmetry of CA, SMA, and IMA arteries was performed using PDS preoperatively in 13 patients with Hirschsprung's disease and 13 healthy age- and sex-matched controls. Diagnostic workup for Hirschsprung's disease included a barium enema and a rectal biopsy. A primary transanal pull through was performed if the transition zone was at rectosigmoid or midsigmoid. Doppler studies were repeated on the 1st and 7th postoperative day under similar conditions. Mean flow velocity (V(mean)) and the pulsatility index (PI) of the three major vessels was measured. RESULTS: Patients with Hirschsprung's disease showed increased blood flow velocities in CA, SMA, and IMA (p < 0.001), an increased resistance to blood flow in IMA (p < 0.001) and a decreased resistance to blood flow in CA and SMA (p < 0.005 and p < 0.001, respectively). The blood flow velocity for IMA normalized after resection of the aganglionic segment (r = 0.41, p < 0.005, 95% CI: 45.4-52.7). CONCLUSIONS: Hirschsprung's diseaseis associated with alterations in splanchnic vessel hemodynamics which are reversible after corrective surgery. Doppler studies may play an important role in the assessment of bowel function after surgery. PMID- 17337893 TI - Bacterial translocation in small intestinal ischemia-reperfusion injury and efficacy of Anti-CINC antibody treatment. AB - The involvement of bacterial translocation in small intestinal ischemia reperfusion injuries and the efficacy of using anti-CINC antibodies for treatment were investigated. A model for ischemia-reperfusion injury of the small intestine was constructed by clamping the supramesenteric artery (for 90 min) in rats. Anti CINC antibodies and saline were given just before the induction of ischemia in the treatment group and the control group, respectively. Six hours after reperfusion, bacteria were detected in the mesenteric lymph nodes, but the 'bacteria-positive' rate was significantly lower in the treatment group than in the control group. Bacterial cultures and endotoxins in the blood were negative in both groups up to 24 h later. The plasma cytokine levels showed similar variations, although the increases were significantly lower after reperfusion in the treatment group. In addition, the degrees of neutrophil infiltration and mucosal injury were attenuated in the small intestine, and the structure of the liver was maintained. Furthermore, the 1-week survival was improved. These results suggest that bacterial translocation occurred predominantly via the lymphatic system and that anti-CINC antibody treatment exerted a protective effect against small intestinal ischemia-reperfusion injury. PMID- 17337894 TI - April 16th: the World Voice Day. AB - Although the voice is used as an everyday basis of speech, most people realize its importance only when a voice problem arises. Increasing public awareness of the importance of the voice and alertness to voice problems are the main goals of the World Voice Day, which is celebrated yearly on April 16th. The event started as a national initiative in Brazil in 1999 and quickly spread internationally. The article provides a brief history of the World Voice Day, together with basic background information. PMID- 17337895 TI - Consonant profile of Arabic-speaking school-age children in Jordan. AB - The paper provides a detailed consonant profile of 100 Jordanian children at the onset of formal schooling. The data were elicited through a modified version of Amayreh's (1994) articulation test. The findings showed that all consonants of Jordanian Spoken Arabic were acquired. The six consonants that were not acquired in Standard Arabic have dialectal forms. The accuracy rates of these consonants were discussed in the light of frequency of occurrence of consonants and diglossia. The study recommended an earlier targeting of consonants that have dialectal variants. It also suggested that knowledge of the diglossic nature of Arabic is important for literacy development as well as for diagnosis and treatment of articulation problems. PMID- 17337896 TI - [Lexical outcomes in auditory closure in children with sensorineural hearing loss]. AB - OBJECTIVE: The aim of this study was to assess the lexical outcomes in auditory closure of children with aided residual hearing. PATIENTS AND METHODS: A total of 37 children (from 4;7 to 8;2 years old) with bilateral (n = 23) or unilateral (n = 14) sensorineural hearing loss (average at frequencies of 0.5, 1, 2, 4 kHz >20 to >90 dB in the better ear) of unknown onset (n = 31) were recruited out of the 1994 implemented Gottinger Hor-Sprachregister (Go HSR). Mean age at diagnosis: 72.0 months (SD 9.8; min. 48; max. 88), mean age at hearing aid implementation: 73.0 months (SD 9.4). All children demonstrated an average nonverbal intelligence, and none suffered from major comorbidities. The subtest 'Auditory Closure' of the standardized (compared to normally developing hearing children) German version of the Illinois Test of Psycholinguistic Abilities was carried out at 3 time points (t1-t3). Mean time interval t1-t3: 20.3 months (SD 4.7). The test raw scores were converted to T scores (mean = 50, SD = 10). The first psychometric examination took place after the ascertainment of the hearing loss (t1). Two follow-ups (t2, t3) were performed at 6- to 9-month time intervals. RESULTS: On average, the study group exhibited age-appropriate performances at t1 and significantly improved over time. The average performance of bilaterally impaired children increased most notably (t1-t3; p = 0.008). Subgrouped by age at diagnosis < or =73 months (cut-off for split-half comparison), the performances at t3 were statistically significantly different from those of t1 (t1-t3; p = 0.002). A multiple regression analysis demonstrated the effect of the ability of auditory closure at t1 (p < 0.001) and of nonverbal intelligence (p = 0.002) on the outcome measure at t3. CONCLUSION: Auditory closure is less determined by degree of hearing loss than by the size of the individual vocabulary and the nonverbal intelligence potential. PMID- 17337897 TI - Scaling voice activity limitation and participation restriction in dysphonic individuals. AB - The purpose of this study was to determine the most appropriate scaling procedure for evaluating voice activity limitation (AL) and voice participation restriction (PR). In a randomly counterbalanced design, 32 dysphonic individuals rated their self-perceived extents of voice AL and PR using two scaling procedures [equal appearing interval (EAI) scaling and visual analogue (VA) scaling]. Results revealed that test-retest reliabilities were similar for the two scaling procedures. The overall extents of voice AL and PR obtained from the two scaling procedures were similar. Moreover, the significant linear relationships obtained between the EAI and VA data of voice AL and PR suggest both dimensions as metathetic in nature. Therefore, either EAI or VA scaling procedure would be considered as appropriate for rating voice AL and PR. However, the relative ease to use by consumers favours the choice of EAI over VA scaling procedure for evaluating voice AL and PR. PMID- 17337898 TI - Toward improved differential diagnosis of adductor spasmodic dysphonia and muscle tension dysphonia. AB - OBJECTIVE: Adductor spasmodic dysphonia (ADSD) is characterized by a strained strangled voice quality, whose diagnosis relies exclusively on auditory perceptual features. However, muscle tension dysphonia (MTD) -- a functional voice disorder -- can mimic ADSD thereby contributing to diagnostic confusion. Unlike MTD, ADSD has been described as 'task-specific', implying that certain vocal tasks such as sentences loaded with predominantly voiced consonants will provoke greater sign expression. This investigation examined the diagnostic value of variable sign expression based upon phonetic loading as a means to disambiguate ADSD and MTD. PATIENTS AND METHODS: Five listeners, who were blinded to the purpose of the study, used a 10-cm visual analog scale to rate the dysphonia severity of two sentences (one all-voiced and one containing primarily voiceless consonants) produced by participants with ADSD (n = 29) or MTD (n = 33). RESULTS: A mixed-design ANOVA, with Group (ADSD vs. MTD) as the between subjects variable and Sentence Type (all-voiced vs. voiceless) as the within subjects variable, confirmed a significant Group-by-Sentence Type interaction effect (p = 0.0002). In ADSD, ratings of dysphonia severity for the all-voiced sentence were significantly more severe than for the voiceless sentence (p < 0.0001), whereas in MTD no significant difference was observed (p = 0.9981). The ROC curve confirmed that differences in dysphonia severity between voiced and voiceless sentences represented a highly specific (88-100%), but only 48% sensitive diagnostic marker. CONCLUSIONS: Phonetic loading influences sign expression in ADSD, and assists in discriminating ADSD from MTD. PMID- 17337899 TI - The validity of a simple outcome measure to assess stuttering therapy. AB - OBJECTIVE: The validity of a simple and not time-consuming self-assessment (SA) Scale was tested to establish progress after or during stuttering therapy. PATIENTS AND METHOD: The scores on the SA scale were related to (1) objective measures (percentage of stuttered syllables, and syllables per minute) and (2) (self-)evaluation tests (self-evaluation questionnaires and perceptual evaluations or judgments of disfluency, naturalness and comfort by naive listeners). Data were collected from two groups of stutterers at four measurement times: pretherapy, posttherapy, 12 months after therapy and 24 months after therapy. The first group attended the Comprehensive Stuttering Program: an integrated program based on fluency shaping techniques, and the second group participated in a Dutch group therapy: the Doetinchem Method that focuses on emotions and cognitions related to stuttering. RESULTS: Results showed similar score patterns on the SA scale, the self-evaluation questionnaires, the objective measures over time, and significant correlations between the SA scale and syllables per minute, percentage of stuttered syllables, Struggle subscale of the Perceptions of Stuttering Inventory and judged fluency on the T1-T2 difference scores. CONCLUSION: We concluded that the validity of the SA measure was proved and therefore encourage the use of such an instrument when (stuttering) treatment efficacy is studied. PMID- 17337900 TI - Factors associated with seven-year incidence of diabetes complications among older Mexican Americans. AB - BACKGROUND: Diabetes is common in elderly persons and is highly prevalent in Mexican Americans. Little is known about factors associated with the incidence of diabetes complications. OBJECTIVE: To examine the social, demographic and health factors associated with a 7-year incidence of diabetes complications among older Mexican Americans with diabetes. METHODS: A 7-year prospective cohort of 536 non institutionalized Mexican Americans aged > or =65 years with diabetes residing in the Southwest of USA. Measures included socio-demographic factors, duration of diabetes, diabetes treatment, medical conditions and body mass index. Diabetes complications were assessed by self-reports of any kidney, eye and circulation problems or amputation due to diabetes over a 7-year period. RESULTS: Subjects with disease duration of > or =10 years were found to have an increased incidence of kidney, eye and circulation problems or amputation over a 7-year period. Hazard ratio (HR) for circulation problems was significantly higher in foreign born subjects with >15 years in the USA. Foreign-born subjects with <15 years in the USA and those with a frequent number of physician visits were at increased risk of kidney complications. Subjects with baseline eye complications had a higher HR for incidence of amputations in the next 7 years. Subjects with baseline circulation complications had a higher incidence of amputations, eye and kidney complications in the next 7 years. CONCLUSIONS: Our data suggest that risks of diabetes complications are influenced by different factors. Prolonged diabetes duration, being foreign-born, living in the USA for a longer period, and frequent physician visits were factors associated with diabetes complications. Designing intervention strategies to reduce diabetes complication risks requires an understanding of the differences in demographic and health predictors of such risks. PMID- 17337901 TI - Diagnostic value of salivary cortisol in children with abnormal adrenal cortex functions. AB - AIMS: It has been shown that the free cortisol level in saliva may reflect plasma free cortisol. The measurement of cortisol in saliva is a simple method, and as such it is important in the pediatric age group. In this research, the diagnostic value of measurement of salivary cortisol (SC) measurement was examined in adrenal insufficiency (AI). METHODS: Fifty-one patients, mean age 10.8 +/- 4.29, who were investigated for possible AI, were included. Basal cortisol levels were below 18 microg/dl. Adrenal function was determined by low-dose ACTH test. During the test, samples for SC were obtained simultaneously with serum samples (at 0-10 20-30-40 min). RESULTS: Mean basal serum cortisol level was 8.21 +/- 4.10 microg/dl (mean +/- SD). Basal SC was correlated to basal serum cortisol (r = 0.64, p < 0.001). A cut-off of 0.94 microg/dl for SC differentiated adrenal insufficient subjects from normals with a sensitivity and specificity of 80 and 77%, respectively. A peak SC less than 0.62 microg/dl defined AI with a specificity of 100%; however, sensitivity was 44%. CONCLUSION: Measurement of SC may be used in the evaluation of AI. It is well-correlated to serum cortisol. Peak SC in low-dose ACTH test can be used to differentiate patients with AI in the initial evaluation of individuals with suspected AI. PMID- 17337902 TI - Effects of growth hormone therapy on glucose metabolism and insulin sensitivity indices in prepubertal children with Prader-Willi syndrome. AB - In Prader-Willi syndrome (PWS) growth hormone therapy (GHT) improves height, body composition, agility and muscular strength. In such patients it is necessary to consider the potential diabetogenic effect of GHT, since they tend to develop type 2 diabetes, particularly after the pubertal age. The aim of our study was to investigate the effects of GHT on glucose and insulin homeostasis in PWS children. An oral glucose tolerance test (OGTT) was performed in 24 prepubertal PWS children (15 male, 9 female, age: 5.8 +/- 2.8 years), 16 were obese (group A) and 8 had normal weight (group B), before and after 2.7 +/- 1.3 years GHT (0.22 +/- 0.03 mg/kg/week) and, only at baseline, in 35 prepubertal children with simple obesity (19 male, 16 female) (group C). Fasting glucose and insulin, glucose tolerance, insulin sensitivity index (ISI), homeostasis model assessment of insulin resistance (HOMA-IR), quick insulin check index (QUICKI), area under the curves (AUC) of glucose and insulin were estimated. At the start of GHT, all PWS children were normoglycaemic and normotolerant but two developed impaired glucose tolerance after 2.2 and 1.9 years of therapy, respectively. At baseline, group A showed lower fasting insulin levels, HOMA-IR and AUC of insulin, higher ISI, QUICKI and AUC of glucose than group C. Comparing groups A and B, AUC of insulin was higher and ISI lower in group A. During GHT, a significant increase of fasting insulin and glucose, a worsening of insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) was found only in group A while ISI did not change. The AUC of glucose decreased in both groups instead AUC of insulin did not change. BMI-SDS decreased in group A and increased in group B. The increased insulin resistance and decreased insulin sensitivity in obese PWS patients, as well as the occurrence of impaired glucose tolerance during GHT, suggest that a close monitoring of glucose and insulin homeostasis is mandatory, especially in treated obese PWS children. PMID- 17337903 TI - Longitudinal assessment of levo-thyroxine therapy for congenital hypothyroidism: relationship with aetiology, bone maturation and biochemical features. AB - AIMS: To evaluate therapy and dose adjustments in patients with congenital hypothyroidism (CH), longitudinally followed up until 16 years old, according to aetiology, Beclard's nuclei presence, and thyroxine (T4) level at diagnosis. METHODS: L-T4/kg/day and dose change ratio (CR) were assessed in 74 CH patients. RESULTS: The dose was statistically larger in athyreosis than in dyshormonogenesis (1-10 and beyond 14 years) and in ectopy (2, 15, 16 years). The ectopic children required statistically larger L-T4/kg than the dyshormonogenetic ones (3-7 years). The L-T4/kg/day was increased, not statistically, in patients or with T4 <30 nmol/l or without Beclard's nuclei at diagnosis. The CR progressively dropped after the 6th month at each attendance, without any difference in terms of aetiology, T4 level at diagnosis, or Beclard's nuclei. The total CR was greater (significantly) in patients without Beclard's nuclei, and (not significantly) in those with T4 <30 nmol/l at diagnosis or with agenesia. CONCLUSION: The L-T4 dose in CH is highly affected by the aetiology. The CR is higher in patients with delayed bone maturation at diagnosis. We suggest that these latter patients need blood tests more frequently to obtain a proper titration of the therapy. PMID- 17337904 TI - Enhanced stretch-induced myogenic tone in the basilar artery of spontaneously hypertensive rats. AB - We investigated if the magnitude of myogenic tone in the basilar artery of SHR differs from that in WKY and, if so, whether RhoA- or PKC-dependent mechanisms were involved. Myogenic tone was developed in response to stretch. Stretch induced myogenic contraction was significantly greater in the SHR than WKY in the presence of external Ca(2+). However, in the absence of external Ca(2+), stretch did not evoke a myogenic tone. The [Ca(2+)](i)-induced contraction was larger in SHR than WKY and the [Ca(2+)](i)-force curve was significantly shifted to the left in SHR compared to WKY. Y-27632 significantly inhibited stretch-induced myogenic tone, but the inhibitory effect was larger in the SHR than WKY. However, PKC inhibitors had no significant effect on the myogenic tone. RhoA and PKCepsilon were expressed at higher levels in the SHR compared to the WKY. RhoA and PKCalpha translocated from the cytosol to the cell membrane in response to stretch in both animals, but PKCepsilon was translocated only in SHR. Our results strongly suggest that stretch-induced myogenic tone is enhanced in SHR, and the activation of RhoA/Rho kinase plays an important role in the enhanced myogenic tone in SHR. PMID- 17337905 TI - TGF-beta1 upregulation in the aging varicose vein. AB - BACKGROUND: Although the etiology of venous insufficiency is not well understood, immune response and aging are beginning to emerge as contributing factors. Factors involved in tissue remodeling such as TGF-beta(1) also seem to play an important role in extracellular matrix production. The aim of this study was to explore the relationship between chronic venous insufficiency and TGF-beta(1) examining the latent/mature form of TGF-beta(1) and the presence of mast cells. Effects of age were also evaluated. METHODS: Saphenous veins were obtained from patients subjected to aortocoronary bypass (controls) and undergoing varicose vein surgery. These were immunolabeled using anti-LAP TGF-beta(1)/anti-TGF beta(1) antibodies and subjected to Western blot. Mast cell population was identified by metachromatic staining. RESULTS: Latent TGF-beta(1) was significantly reduced in varicose veins from older subjects. In contrast, smooth muscle cells obtained from the varicosities showed intense levels. Mature TGF beta(1) significantly differed between healthy and varicose veins. No mature TGF beta(1) was detected in the cell cultures. Mast cell number and degranulation were increased with aging and varicose disease, colocalizing with the mature form of TGF-beta(1). CONCLUSION: Aging and varicose pathology induce dysregulation of TGF-beta(1) that could play an important role in the fibrous process, representing the final stages of venous insufficiency. PMID- 17337906 TI - Basement membrane remodeling in skeletal muscles of patients with limb ischemia involves regulation of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases. AB - BACKGROUND/AIM: Because the pericapillary basement membrane in skeletal muscles of patients with chronic critical limb ischemia (CLI) is thickened, we determined the expression patterns of genes involved in collagen metabolism, using samples from 9 CLI patients, 4 patients with acute limb ischemia and 4 healthy controls. METHODS: Gene array analysis, quantitative RT-PCR and semiquantitative grading of immunohistochemical reactivity were performed to determine mRNA/cDNA and protein concentrations. RESULTS: In CLI patients compared to controls, cDNA levels of matrix metalloproteinase (MMP)-9 and MMP-19 were higher, collagen type IV chains A1 and A2, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 were similar and MMP-2 were lower. On the protein level, MMP-2, MMP-9, MMP-19 and TIMP 1 were more abundantly expressed. In skeletal muscles from patients with acute limb ischemia, cDNA and protein levels of MMP-9, MMP-19, collagen type IV chains, TIMP-1 and TIMP-2 were high. MMP-2 was elevated at the protein but decreased on the cDNA level. CONCLUSION: Expression of basement membrane components in skeletal muscles of CLI and acute limb ischemia patients is altered, possibly contributing to the pathogenesis of peripheral arterial disease. PMID- 17337907 TI - Peptidoglycan increases firm adhesion of monocytes under flow conditions and primes monocyte chemotaxis. AB - The Toll-like receptor (TLR) 2/nucleotide-binding oligomerization domain ligand peptidoglycan (PG) has been shown to be present in macrophage-rich regions within atherosclerotic lesions, and stimulation of TLR2 promotes atherosclerotic plaque and intima formation in in vivo mouse models. We determined the effect of a PG preparation and Pam(3)Cys-SK(4), a synthetic TLR2 activator, on (1) adhesion molecule expression by flow cytometry; (2) monocyte adhesion under flow conditions, and (3) monocyte migration. The total adhesion (rolling and firm adhesion) of the PG-preparation-stimulated monocytes to L cells, constitutively expressing ICAM-1 (intercellular adhesion molecule-1) and E-selectin, was decreased. This was most likely due to the L-selectin shedding, since monocyte incubation with a blocking L-selectin antibody resulted in a comparable number of adherent monocytes as PG-stimulated cells. The PG preparation induced an increased percentage of firmly adherent, polarized cells and a beta(2)-integrin dependent binding to ICAM-1-coated beads. Interestingly, the PG preparation induced a priming of the monocytes for increased migration towards the chemoattractant C5a which was TLR2 and beta(2)-integrin dependent. Pam(3)Cys SK(4) gave comparable results to the PG preparation in all assays tested. This study demonstrates that PG activation of monocytes results in an increase in adhesive and migratory capacities of these cells. This might be a mechanism by which PG promotes atherosclerotic disease in vivo. PMID- 17337908 TI - The effects of endothelial factor inhibition on the time course of responses of isolated rat coronary arteries to intraluminal flow. AB - The aims of this study were to investigate, for the first time, the effects of endothelial factor inhibition on both the magnitude and dynamics of the response of isolated small coronary arteries to intraluminal flow. Isolated rat coronary arteries were mounted on a pressure myograph and left to develop myogenic tone. Flow was introduced and maintained until stable diameters were attained. Dilatory responses were observed which were maximal at low flow rates (5-10 microl/min) and thus shear stresses (1-2 dyn/cm(2)). These responses were transient in nature. Transient dilations were also observed upon cessation of flow. All responses (to 5 microl/min) were endothelium dependent and were completely abolished by addition of charybdotoxin (100 nM) and apamin (100-500 nM) suggesting an important role for a hyperpolarizing mechanism most likely involving an endothelium-derived hyperpolarizing factor. However, inhibitors of nitric oxide synthase (L-NNA; 100 microM) or cyclo-oxygenase (indomethacin; 10 microM) also modulated the response causing an increase and decrease in maximum vasodilation, respectively. By examining the time course we showed that both agents also made the response significantly more transient in nature. These results show that inhibition of endothelial factor pathways can influence both the magnitude and dynamics of the response of isolated rat coronary arteries to flow. PMID- 17337909 TI - Transglutaminase 1 stabilizes beta-actin in endothelial cells correlating with a stabilization of intercellular junctions. AB - Microvascular endothelial monolayers from mouse myocardium become resistant to various barrier-compromising stimuli correlating with the expression of transglutaminase 1 (TGase1) and its translocation towards cellular junctions. In contrast, endothelial monolayers from mouse lung microvessels do not express TGase1 and remain sensitive to barrier-compromising stimuli corresponding to the known in vivo sensitivity of the lung microvasculature. Using the TGase-substrate 5-(biotinamido)-pentylamine, specific TGase inhibitors and RNAi, one target protein of TGase1 in endothelial cells was found to be beta-actin, suggesting that tissue-specific stabilization of the cortical actin filament network by intracellular TGase1 activity may play a role in controlling barrier properties of endothelial monolayers. PMID- 17337910 TI - Role of combined L-arginine and prostaglandin E1 in renal ischemia-reperfusion injury. AB - BACKGROUND: L-Arginine (L-arg) and Prostaglandin E(1) (PGE(1)) have been used effectively as single agents to ameliorate renal ischemia-reperfusion injury. We hypothesized that combined treatment with L-arg and PGE(1 )would be more effective. MATERIALS AND METHODS: The left renal artery of male Sprague-Dawley rats was clamped for 45 min and the right kidney was removed. Fifty six rats were randomly allocated into 5 groups each consisted of 12 rats except sham group (n = 8). (1) sham, underwent right nephrectomy only; (2) control, untreated ischemic rats; (3) L-arg group, L-arg-treated ischemic rats; (4) PGE(1) group, PGE(1) treated ischemic rats; (5) L-arg+PGE(1) group, ischemic rats treated with both L arg and PGE(1). Renal function and histology were assessed on days 2 and 7 postoperatively. RESULTS: All rats, except control ones, showed a significant improvement of renal function towards normal on postoperative day 7. Serum creatinine and creatinine clearance were significantly better in L-arg+PGE(1) group compared to all other groups on day 7. With the exception of sham-operated and L-arg+PGE(1)-treated animals, all other groups showed significant increases in fractional excretion of sodium (FE(Na)) in response to renal ischemia reperfusion. The severest tubular damage was determined in the kidneys of control rats. Rats treated with L-arg+PGE(1) had the least severe tubular damage. CONCLUSION: The administration of either L-arg or PGE(1) attenuates both functional and structural consequences of renal warm ischemia. A near total protection might be achieved when both agents are administered concomitantly. PMID- 17337911 TI - The relationship between protein C, protein S and cytokines in acute ischemic stroke. AB - OBJECTIVE: The role of inflammation in the pathogenesis of acute ischemic stroke is well known, but its association with the clinical picture is as yet unclear. MATERIAL AND METHODS: In our study, we measured the serum levels of the proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) within the first 50 h of stroke in 60 acute stroke patients, and examined the association with the natural anticoagulants protein C and free protein S. We compared the results with a control group that consisted of 30 volunteers. We also correlated their levels with the clinical outcomes by using the Canadian Neurological Scale (CNS). RESULTS: Neither stroke patients nor the control group had any elevations in IL 1beta serum levels. However, the levels of serum IL-6 were significantly higher in stroke patients (13.7 +/- 19.46 vs. 4.3 +/- 15.88, p = 0.002). In addition, the protein S levels of patients were lower than those of the controls (84.36 +/- 27.97 vs. 95.9 +/- 25.64, p = 0.007). Although IL-6 showed negative correlation with protein S (r = -0.504, p = 0.000), the other studied cytokines TNFalpha and IL-1beta did not correlate with these natural anticoagulants. Another negative correlation was found between IL-6 and CNS scores (r = -0.451, p = 0.000). In addition, both protein C and protein S positively correlated with CNS (r = 0.263, p = 0.042; r = 0.381, p = 0.003). There was also a positive correlation between protein C and protein S (r = 0.408, p = 0.001). CONCLUSIONS: Our results suggest that TNFalpha and IL1beta serum levels are not elevated in the acute phase of stroke and have no correlation with the natural anticoagulants protein C and protein S. However, a decrease in free protein S may be related to elevated IL-6 levels. In addition, increased levels of IL-6 and reduced levels of protein C and protein S may play a role in acute ischemic stroke severity. PMID- 17337912 TI - Immunotherapy of prolactinoma with a T helper 1 activator adjuvant and autoantigens: a case report. AB - OBJECTIVE: To date, efforts to reliably manipulate the immune system to promote tumor regression in the brain have been disappointing. We report a unique experience of successful immunotherapy to treat a pituitary macroprolactinoma. METHODS: A 31-year-old woman with an established history of pituitary macroprolactinoma who had undergone tumor resection followed by radiation was admitted to our clinic. The diagnosis had been made due to the patient's symptoms, a serum prolactin (PRL) level of 29,600 mIU/l, a brain MRI revealing a 23 x 19 x 18 mm pituitary mass and a positive PRL immunohistochemistry of the mass. Six months following surgery, she reexperienced headache, excessive sweating and a serum PRL concentration of 2,960 mIU/l despite receiving 30 mg/day bromocriptine. Brain MRI revealed a pituitary mass (3 x 6 x 8 mm) compatible with a pituitary adenoma. Twenty micrograms per milliliter of G2 (as a T helper 1 activator adjuvant) was inoculated intradermally once per week for 24 consecutive weeks (each injection contained 10 mug of G2). The autoantigens were inoculated at the same time with G2. RESULTS: After immunotherapy, serum PRL concentration decreased to 82 mIU/l, the patient's symptoms disappeared, skin thickness increased to normal and bromocriptine dosage was tapered to 20 mg per week. A follow-up brain MRI revealed almost complete disappearance of the tumor. The patient does not complain of any problems at 1-year follow-up. CONCLUSION: Activation of both nonspecific (natural killer cells) and specific (cytotoxic T lymphocytes) immunity in relation to the T helper 1 cytokine network is a promising strategy for the treatment of tumors of the central nervous system in humans, especially pituitary macroprolactinomas. PMID- 17337913 TI - Safety and efficacy of oral escitalopram as continuation treatment of intravenous citalopram in patients with major depressive disorder. AB - The objective of this open-label, multicentre study was to evaluate the safety and efficacy of treatment with escitalopram (10 or 20 mg/day) for 6 weeks following a switch from intravenous citalopram treatment (20 or 40 mg/day) in patients presenting with a major depressive episode. A total of 173 patients were included, 147 (85%) of whom completed the study. The mean Montgomery-Asberg Depression Rating Scale (MADRS) total score at inclusion (last citalopram dose) was 31.6 +/- 9.9. The MADRS score decreased to 23.4 +/- 10.5 after 3 days of oral treatment with escitalopram and was 12.7 +/- 9.3 at the end of the study. The scores on the Clinical Global Impression (CGI) and Patient Global Evaluation scales also improved: at the end of the study, the response rates were 67% on the MADRS (defined as >or=50% decrease from MADRS baseline score) and 68% on the CGI I (defined as CGI-I or = 3.5 for N/L and > or = 12000/mm3 for leukocytosis. N/L ratio > or = 3.5 occurred to have much higher sensitivity (77.5% vs. 55%) but lower specificity (73.3% vs. 81.6%) than leukocytosis. Both leukocytosis and N/L had satisfactory values of prediction and likelihood ratio for positive ad negative results. CONCLUSIONS: (1) N/L ratio has higher sensitivity than leukocytosis, especially in appendicitis phlegmonosa and gangrenosa. (2) Both leukocytosis and N/L ratio have quite high specificity. In cases other than appendicitis that have similar clinical symptoms and are ultimately diagnosed intraoperatively, the N/L ratio and leukocyte count are rarely elevated above 3.5 and 12000/mm3 respectively. (3) Due to easiness of calculation and still high rate of false positive and negative diagnoses, N/L ratio is worth using in establishing the diagnosis of appendicitis. PMID- 17338114 TI - [Characteristics of acute, hemodynamically stable pulmonary embolism presenting as a syncope]. AB - Syncope (S) occurs in approximately 10% patients with acute pulmonary embolism (APE) and is commonly ascribed to the massive, hemodynamically instable APE. The aim of the study was to assess the occurrence and significance of S revealing hemodynamically stable APE. We found syncope in 6 of 21 (29%) consecutive patients (16 females, 5 males; age from 46-87 years, mean age of 71 years) who were diagnosed with APE and in whom other reasons for S were excluded. All patients were treated with anticoagulation. They all survived hospitalization and no APE recurrences were found during in-hospital period. Patients with APE-S compared to patients with APE and without S had smaller baseline RVED (21.2 +/- 2 vs. 27.3 +/- 5.6, p = 0.01), however both groups did not differ statistically in baseline vital signs, angiographic, hemodynamic, other echocardiographic parameters as well as in the results of laboratory findings. It is concluded, that S signals hemodynamically stable APE more frequently than is quoted. APE-S patients could not be clearly discriminate from APE patients without S on the basis of the parameters studied and S did not impact the course of APE during in- hospital period. PMID- 17338115 TI - Iodine excretion with urine and thyrotrophic hormone concentration in normal and complicated pregnancies in the industrial region of iodine deficiency. AB - A sufficient amount of iodine in food is necessary for the thyroid gland to produce hormones during pregnancy. The aim of our work was to evaluate iodine and thyrotrophic hormone (TSH) concentration in urine, free triiodothyronine (fT3) and thyroxine (fT4) in complicated pregnancies in Upper Silesia (region of iodine deficiency in Poland) in comparison with normal pregnancies. In both groups the iodine content in urine was evaluated by a quick test and serous concentrations of TSH, fT3 and fT4 were determined by a radioimmunological method. We found the iodine excretion with urine below 100 microg/L in 29.15% of all women under study, i.e. an insufficient supply of this element. The reduced iodine concentration in urine was found to be more often in women with imminent premature delivery. Moreover, it was found that in II trimester the concentration of iodine excreted with urine had been significantly lower comparing to the patients examined in III trimester. We found significantly higher concentration of thyrotrophic hormone in pregnant women with iodine excretion below 100 microg/L of urine. Evaluation of the iodine concentration in urine may be a simple screening test to determine the supply of this element in a diet. Moreover, our studies demonstrate the necessity for the iodine supplementation in pregnant women in the Silesian region--an area of iodine deficiency in Central Europe. PMID- 17338116 TI - [Assessment of microcirculatory system with conventional capillaroscopy in patients with rosacea--preliminary study]. AB - Capillary microscopy is a non-invasive method, without any risk, easy to assess a microvascular abnormalities and influence of therapeutic methods. The aim of the study was to assess in conventional in vivo capillary microscopy a microvascular condition and its abnormalities in nail bed in patients with diagnosed rosacea in various clinical stages. MATERIAL AND METHODS: 16 female patients with diagnosed rosacea have undergone the clinical and capillary microscopic examination. The results were compared with healthy group of volunteers (16 females) . The results of clinical and microvascular studies in observed patients were shown. RESULTS: The age of patients with rosacea was between 20 and 70 years, average age was 49.38 years (SD 12.81 years). In the volunteers group the average age was 38.75 years, SD 9.48 years (min. 27, max. 55 years). A clinical type was categorized due to Plewig and Kligman classification. In the I stage there were 4 persons, in II--9 and in III phase--3 patients. The mean duration of rosacea was 5.56 years (SD 4.7 years). In the capillaroscopic examination in all patients with rosacea atypical capillaries were found. The abnormal capillaries were present in 10 volunteers (63%). In the rosacea group the most common occurred: Raynaud loops in 10 cases (62.5%), meandering capillaries and their elongation also in 10 patients (62.5%) and increasing number of the capillaries in 13 examined persons (81.25%). In the control group the presence of stenosed capillaries was confirmed in 3 examined persons (18.75%) with good visualized subpapillary venous plexus also in 3 cases (18.75%). In the rosacea group abnormalities of the color of the visual area were proved in 14 cases (88%) with indistinct field of vision in 3 cases (19%). In the control group the color of field of vision was normal in 11 examined persons (69%) and no abnormalities of visual area acuity were reported. CONCLUSION: Examination proved that conventional capillaroscopy seems to be a new diagnostic method in rosacea. PMID- 17338117 TI - [Contemporary spouses and family childbirth]. AB - Contemporary science is aiming at restoring the childbirth its family character. However, realization of this undertaking demands care from parents' side, who should aim at gaining the highest quality of experiences connected with the childbirth. The aim of this work was to check whether contemporary spouses decide on the family childbirth in hospital, what are the conditions of such decisions and what are the women's experiences connected with giving the birth. 180 women have taken part in the research in their procreational age. Taking part in this research was voluntary and anonymous, the choice of fate. The results of this work showed that the majority (71.1%) of women had delivered the child in a traditional way, however the decision on the form of the delivery depended on their job activity and whether it was a planned pregnancy. In the opinion of women (72.8%) the delivery was a source of negative feelings, however it was the case in the majority of women who gave birth in a traditional way. PMID- 17338118 TI - [Serum levels of interleukin-6 and interleukin-10 in patients with multiple sclerosis during intravenous immunoglobulin infusion]. AB - Intravenous immunoglobulin (IVIG) therapy is a recognized treatment of inflammatory and autoimmune disorders and its efficacy in multiple sclerosis (MS) has been proven in a few double-blind studies. IVIG has several effects on the immune system that could have a beneficial influence on disease process in MS and one of these effects are significant changes in serum levels of circulating cytokines after IVIG infusions. As interleukin-6 (IL-6) and interleukin-10 (IL 10) play important role as pro- and anti-inflammatory factors, in vivo modulation of these cytokines may account for immunomodulatory and anti-inflammatory effect of IVIG therapy. In order to better understand mechanism of action of low-dose IVIG cyclic therapy we have investigated serum levels of IL-6 and IL-10 before and a day after IVIG infusion in patients with MS. MATERIAL AND METHODS: Serum levels of IL-6 and IL-10 were assayed in 20 patients with MS before and 24 hours after infusion of 2.5 g (n = 9) and 5 g (n = 11) of IVIG. RESULTS: Significant changes of IL-6 nor IL-10 serum levels after IVIG infusions in both doses of 2.5 g and 5 g were not observed. CONCLUSION: Single infusion of 2.5 g nor 5 g of IVIG does not alter serum levels of neither pro-inflammatory IL-6 nor anti inflammatory IL-10. As modulating influence of IVIG on the serum levels of IL-6 and IL-10 seems to be dose-dependent, further investigations of these cytokines levels after infusions of higher doses of IVIG might be efficient in the assessment of its usability in monitoring of immune system response to IVIG treatment. PMID- 17338119 TI - [Comparison of analgetic effect of magnetic and laser stimulation before oral surgery procedures]. AB - Oral surgery procedures are often the cause of painful sensations because of their tissue invasiveness. To avoid these sensations a wide use of nonsteroid antiinflammatory drugs is usually accepted. Because of plenty side effects of these drugs alternative antipain agents are desired. The goal of this study was to assess antipain effect of laser stimulation and alternating magnetic field in oral surgery procedures. Pain sensations in patients during: local anesthetics application, surgical procedure and after it were assessed according to VAS scale. Level of stomatological fear was assessed with the use of Corah's scale. Achieved results were analyzed statistically. Conclusion of this analysis is that laser stimulation and alternating magnetic field applied directly before oral surgery procedure are effective antipain agents that decrease intra and postoperative sensations. It was observed that patients with high level of stomatological fear had more pain sensations but even in this group laser and magnetic stimulation significantly lowered these complaints. PMID- 17338120 TI - [Apigenin inhibits release and gene expression of monocyte chemoattractant protein 1 (MCP-1) in J774.2 macrophages]. AB - Monocyte chemoattractant protein-1(MCP-1) is secreted by activated macrophages and endothelial cells, and is involved in the pathogenesis of cardiovascular and neurodegenerative disorders. There is need to develop drugs that inhibit excessive infiltration of monocytes and lymphocytes to the arterial wall and central nervous system. The aim of this study was to evaluate the effect of apigenin on the synthesis and release of MCP-1 by J774.2 macrophages in vitro. Apigenin studied at higher doses (10 and 30 microM) diminished MCP-1 release in lipopolysaccharide activated J774.2 macrophages. Apigenin administered at lower doses (3.1 and 0.3 microM) did not change secretion of MCP-1 in LPS-stimulated macrophages. Apigenin treated at a dose of 30 microM strongly reduced the number of MCP-1 mRNA copies in J774.2 cells. These results suggest that apigenin possesses anti-inflammatory properties and that apigenin inhibited MCP-1 production at the transcriptional level. PMID- 17338121 TI - [Prevalence of autoimmunological disorders of the thyroid in children in the Bialystok population]. AB - Up-to-date observations in the regions where effective food iodine supplementation was introduced confirm a significant decrease in goiter incidence. However, in some regions the incidence of goiter remains unchanged or even the increase in the frequency of autoimmunological diseases of the thyroid like, Grave's-Basedov disease and chronic/subacute lymphocytic thyroiditis is observed. The purpose of the study was to evaluate the prevalence of autoimmunological diseases of the thyroid in children aged 6-13 years in the Polish population after 5 years of obligatory iodine supplementation program. The study included 480 school children from 4 elementary schools chosen randomly in the city of Bialystok and 120 patients at the same age treated due to goiter with KI and/or thyroxin for minimum 12 months in the Regional Specialist Outpatient Clinic of Endocrinology. All children underwent physical examination with palpation of goiter and USG of the thyroid. Iodine concentration was assessed in the morning urine by the catalytic method of Sandell-Kolthoff. The concentrations ofTSH and antibodies against TSH, thyroid-peroxidase (TPO) and thyroglobulin (Tg) were also determined. The mean concentrations of anti-Tg antibodies were statistically significantly higher in children with goiter in comparison with children with the thyroid gland within the norm (155.8 IU/ml vs. 24.4 IU/ml, p = 0.045). In children with goiter the incidence of'positive' titre of anti-Tg antibodies was 4-fold as high as in children without goiter (33.3% vs. 8.7%, p = 0.0147). High incidence of antibodies against thyroglobulin in the population of children with goiter and a positive correlation between the titre of anti-Tg antibodies and the size of the thyroid in this group suggest a significant role of autoimmunological disorders in the pathogenesis of goiter in the studied population. PMID- 17338122 TI - [Changes in the percentage of activated lymphocytes in bronchoalveolar lavage fluid in patients with clinical improvement of sarcoidosis]. AB - Sarcoidosis is characterized by an accumulation of the activated lymphocytes in affected organs. The aim of the study was the analysis of lymphocytes activation markers in a bronchoalveolar lavage fluid (BALF) in sarcoidosis and the influence of the disease outcome on the changes of cells subpopulations. MATERIAL AND METHODS: We performed the study on 12 patients with the regression of sarcoidosis after the mean period of the observation 8.1 +/- 3.8 months. RESULTS: We observed a tendency toward a BALF cellularity normalization: lowering of the percentage of CD4+ lymphocytes (mean: 67.1% vs. 57.8%, p = 0.047), lowering of the CD4+/CD8+ ratio (mean: 6.3 +/- 5.4 vs. 3.7 +/- 5.2, p < or = 0.05), lowering of the percentage of HLA-DR+ lymphocytes (mean: 65% < or = 16.4 vs. 43.9% +/- 18.0, p = 0.05), lowering of the percentage of CD25+ lymphocytes (mean: 5.7% vs. 3.1%, p < or = 0.05) and CD4+CD25+ (mean: 4.0% vs. 2.4%, p = 0.011). CONCLUSION: The clinical improvement of sarcoidosis is accompanied by the lowering of the percentage of activated lymphocytes in BALF. PMID- 17338123 TI - [Effect of low doses of metoprolol, bisoprolol and carvedilol on mortality in patients with left ventricular dysfunction after acute myocardial infarction]. AB - Beta-blocking agents (B-A) in patients with postinfarction left ventricular dysfunction or heart failure reduce the risk of death. Some patients do not tolerate high doses of medications which benefit was well documented in multicentre trials. The purpose of this study was to evaluate the effect of low dose of metoprolol, bisoprolol and carvediolol on mortality in postinfarction (post-MI) patients (pts) with depressed < or =35% left ventricular ejection fraction (EF) in 24-month observation. MATERIAL AND METHODS: Study population consisted of 74 pts, (59 men and 15 women) aged 38-79 years (mean age 62 +/- 11 years) with post-MI left ventricular dysfunction (EF < or = 35%). Patients were divided into 2 groups according to applied treatment: the group B-A(+) included 55 pts who received during hospitalization and ambulatory observation beta blockers in low doses: metoprolol in the dose of 25-75 mg/day (mean 56 +/- 20 mg/day), bisoprolol in the dose of 2,5-5 mg/day (mean 3.1 +/- 1.2 mg/day) or carvedilol in the dose of 6.25-12.5 mg/day (mean 9.1 +/- 3.3 mg/day) and the group B-A(-) - 19 pts not treated with beta-blocking agents. RESULTS: During long term observation 24 from 44 patients died (32%). All causes mortality in the group B-A(+) - 18/55 (33%) did not differ from mortality in the group B-A(-) - 6/19 (32%). CONCLUSION: In patients with depressed < or =35% ejection fraction after acute myocardial infarction treatment with low doses of metoprolol, bisoprolol and cardvediolol did not reduce mortality rate in 24-month observation. PMID- 17338124 TI - [Close family relationships and the emotional distress in lung cancer patients awaiting surgery and healthy controls]. AB - The purpose of this study was to look for effects of attachment styles for emotional distress presented in depression in 117 lung cancer patients under surgical treatment and in 112 healthy subjects. The three attachment styles were assessed by means of the instrument based on Hazan and Shaver's (1987). Depression was measured by self-reporting Symptom Checklist 90 (SCL-90). Manova variance analysis revealed significant main effect of the factor "group" which indicated higher level of depression in cancer patients than controls, significant main effect of factor "attachment style" which exhibited higher level of depression in the anxious-ambivalent subjects than in the secure ones, significant main effect of interaction between these two factors which revealed higher level of depression in the anxious-ambivalent style in lung cancer patients than in controls. Analysis of correlations indicated that the patients' secure style was adversely associated with depression, the anxious-ambivalent style positively correlated with patients' depression, the avoidant style did not correlate significantly with depression neither in healthy nor affected by the disease subjects. The secure subjects and the avoidant subjects did not differ significantly in the level of depression. The results indicate that the secure style and the avoidant style may protect lung cancer subjects before operation from excessive reacting with distress demonstrated in depressive symptoms. The ambivalent style was favorable for higher depression and it could be a risk factor for mood disorders in clinical group. PMID- 17338125 TI - [The pharmacological treatment of abulic posttraumatic state in children preliminary report]. AB - The aim of the study was the evaluation of clinical condition of the children treated by Gliatilin and Dexamin for posttraumatic abulic state. MATERIAL AND METHOD: The study included 12 children (8 boys, 4 girls) at the age range between 7-16 years (mean age 7.8 years). The evaluation of clinical condition was performed on admission to the Department, and then at 3rd, 6th and 12th month after head injury. The authors analyzed the kind of injury (posttraumatic changes in neuroimaging) and evolution of patients' clinical condition in the follow-up. RESULTS: The most commonly observed reasons of trauma were motor vehicle accidents. The kind of pathology found on the base of neuroimaging did not affect the results of treatment. The patients were treated by Gliatilin, Dexamin or both. In spite of this treatment all children were rehabilitated and their hearing, sight and speech organ were stimulated. Six months after injury only one patient still presented abulic state and six of our patients were in good general condition. None of our patients revealed abulic state after 12 months of head trauma. In two children the Dexamin treatment was given up for seizures. We did not observe any side effects of Gliatilin. CONCLUSIONS: The kind of trauma and posttraumatic intracranial pathology do not determine the prognosis. The evaluation of treatment should be performed after 6-12 months. Gliatilin and Dexamin treatment improves the clinical state of patients with posttraumatic abulic state. PMID- 17338126 TI - [Social and healthy circumstances of women's decision about applying hormonal replacement therapy]. AB - The aim of the study was to evaluate the frequency of hormonal replacement therapy (HRT) application among Polish women aged 40-65, patients of five selected health care institutions located in south-eastern Poland and to determine the most significant factors that influence women's decision to initiate HRT. The next purpose was to establish how the women learned about the possibility of receiving HRT. Women, who never decided to take sex hormones, were asked about the reasons of such decision. MATERIAL AND METHODS: The study comprised a group of 1033 women aged 40-65 years living in south-eastern Poland, the patients of various hospital wards and outpatient clinics. The study was conducted from January 2003 to December 2004 using categorized interview technique. The interview questionnaire was constructed by the authors. The statistical analysis was performed on the basis of the chi2 test of independence; log-linear analysis and Pareto's analysis were also used. RESULTS: Research result analysis proves that 30.5% of the examined women have used HRT currently or in the past. The sociodemographic and healthy variables that showed positive correlation with receiving hormonal treatment by midlife women were: age 51-65 years, the presence of climacteric ailments, the absence of monthly bleedings, possessing of permanent life partner and good self-estimation of one's financial status. It was not revealed that better educated women more frequently decide to take HRT. The main sources of women's knowledge about HRT were the mass media and health service employees. Among the reasons for not taking up hormonal treatment the most significant were: lack or small intensification of menopausal ailments as well as the fear of side effects of hormonal replacement therapy. PMID- 17338127 TI - [Isolated right ventricular myocardial infarction in cardiosurgery practice]. AB - Isolated right ventricular myocardial infarction (RVMI) is a very rare complication of ischemic heart disease. Generally it accompanies infero-posterior or antero-septal myocardial infarction cases. Right ventricular myocardial infarction is a strong predictor of acute right ventricular failure, bradyarrythmia, ischemic and mechanical complications and is frequently complicated by cardiogenic shock which often leads to death. Acute right ventricular ischemia (RVI) and RVMI are big problem particularly during and early post-operative cardiosurgery procedures. Atherosclerotic changes and heart blood flow disturbances predispose to RVI or RVMI that occur more often in cardiosurgical patients, especially in early postoperative period. On the other hand early intraoperative diagnosis and longer reperfusion period result in the correction of heart function and better prognosis. PMID- 17338128 TI - [Practical aspects of the diagnosis and treatment of mild chronic bronchial asthma]. AB - Mild chronic bronchial asthma sometimes may be asymptomatic and run without spirometry disturbances despite significant pathophysiological changes in airways. Diagnosis of this kind of asthma consequently is often delayed resulting in improper treatment or even its lack. In this paper pathomechanism and pathophysiology of mild chronic bronchial asthma has been presented. Moreover, step-wise therapeutic procedures, methods of assessment of control of disease symptoms and post-treatment verification of the diagnosis have been discussed. PMID- 17338129 TI - [Apoptosis and necrosis--two different ways leading to the same target]. AB - Both apoptosis and necrosis lead to the same target, i.e. the death of the cell. However their mechanisms are different although they are evoked by similar factors. The differences between apoptosis and necrosis concern not only morphological features but also biochemical changes taking place in the cell. In the case of apoptotic death of cell, its intracellular content is not released and that is why inflammatory reaction, which is present in necrosis, is absent. In necrosis, defined as a passive death, majority of enzymes as well as metabolic tracts are lost and the released lysosome enzymes digest cellular components. Apoptosis, on the other hand, is an active process which requires supply of adenosine triphosphate (ATP) and which is controlled by many genes. There are many factors that determine the kind of cell death. The most important of them seems to be the level of intracellular ATP connected with caspase activation. This is the reason why mitochondria are considered to be the main cell organelles, which determine the type of cell death. Disturbances in the flow of ions connected with the activation of specific ion channels as well as free oxygen radicals are of importance here, too. PMID- 17338130 TI - [The problem of fatigue in neurological disorders]. AB - Fatigue or piercing feeling of weakness, lack of strength and energy or total exhaustion is a common complaint of patients with neurological disorders. From 40 to over 90 per cent of individuals with multiple sclerosis, Parkinson disease, amyotrophic lateral sclerosis, neuroboreliosis, post polio syndrome or stroke confirm its experience. It is not infrequently numbered among most disabling complaints. A separate entity, with fatigue as a cardinal sign, is a chronic fatigue syndrome, a disorder, though controversial, more and more frequently diagnosed. Fatigue ought to be discriminated from fatigability, paresis, somnolence and, first of all depression which commonly coexists in chronic disorders. The assessment is almost entirely based on self-estimate scales filled in by a patient. Attainable results of neuroimaging, electrophysiological, polisomnographic, vegetative, psychological and biochemical surveys have not allowed yet to define the pathogenesis of fatigue. The treatment basis consists of behavioral therapy, psychotherapy and a proper treatment of the basic disease. PMID- 17338131 TI - [Infections in the elderly. Part II. Prevention and treatment]. AB - Infections constitute one of the most important health problems in ageing society. Infection prevention is multifactorial and includes a healthy lifestyle, an appropriate nutrition, regular physical exercises and vaccinations: against influenza, pneumococcal vaccine, against tetanus. Elimination of risk factors is also important, especially in hospitalized and institutionalized elderly: limiting visits during periods of increased incidence, respiratory prophylactics, prevention of aspiration and prevention of urinary tract infections among others by limiting indications for catheterization. Infection treatment in the elderly is often modified due to pathophysiological changes in this age group. The purpose of this article is to present the most important actual information concerning this subject. PMID- 17338132 TI - [Ghrelin, a new hormone involved not only in the regulation of appetite]. AB - Recent progress in the field of energy homeostasis was triggered by the discovery of adipocyte hormone leptin and revealed a complex regulatory neuroendocrine network, which precisely regulates appetite. Discovery of ghrelin, a novel hormone derived from the stomach, has illustrated the relationship of the stomach and hypothalamus which is a crucial missing link in the regulation of energy balance, growth and coordinated gastrointestinal function. The discovery of ghrelin opens new perspectives of research with potential therapeutic relevance in patients with gastrointestinal, metabolic, endocrine and other diseases. PMID- 17338133 TI - [Delusional misidentification syndrome]. AB - The term "delusional misidentification syndrome" (DMS) includes undoubtedly the Capgras syndrome, the Fregoli syndrome, intermetamorphosis and the syndrome of subjective doubles. Until the past decade DMS was regarded as very rare, but an increasing number of cases are now being reported. A range of suggestions has been put forward in order to explain etiopathogenesis of DMS. Psychological and especially psychodynamic viewpoints attributed a decisive pathogenetic role to the defense mechanisms of splitting and projection. DMS was compared with a phenomenon of prosopagnosia. An attempt of theoretical explanations of DMS was information-processing model of familiar face recognition by Bruce and Young. Nowadays event-related potentials, especially auditory P300 component, constitute a useful tool providing valuable information with regard to the brain-behaviour relations. PMID- 17338134 TI - Visceral situs inversus in three patients. AB - Three examples of patients with complete visceral situs inversus are presented from nineteen years of clinical experience. The first case concerns a 16-year-old woman, who suffered from appendicitis and was operated on one day after the admission. The second case presents a 63-year-old woman admitted and operated on because of colorectal carcinoma. The last case involves a 66-year-old man taken in and operated on due to stomach cancer. A surgical patient with complete visceral situs inversus forces an operator to abandon currently used operating standards. This situation should especially mobilize operator's watchfulness while performing the procedure. Non-typical circumstances occurring during operation increase frequency of incidence of intra-operative complications. PMID- 17338135 TI - [Developmental anomaly of superior vena cava as a reason hampering vein-port catheter implantation]. AB - Occasionally unexpected technical difficulties occur during Port-A-Cath implantation and the central venous catheterization. We described a case of superior vena cava developmental anomaly diagnosed during Port-A-Cath implantation. PMID- 17338136 TI - [Dopa-responsive dystonia (Segawa syndrome) with secondary skeleton deformity]. AB - Dopa-responsive dystonia (DRD) is a rare, autosomal dominant (GTP cyclohydroxylase gen mutation on chromosome 14q) or rarely recessive (tyrosine hydroxylase gene mutation on chromosome 11p) inherited disorder. Both enzymes take part in dopamine synthesis. Their deficiencies cause the dopamine level reduction. The first clinical symptoms occur in the childhood. The authors present the case of a 24-year-old woman in whom the lower limb dystonia occurred when she was five. Then the trunk and upper limbs dystonia appeared with skeleton deformities leading to deep disability. DRD was recognized when she was 19 and L Dopa was administered. The clinical status improved, dystonic movements disappeared completely. The authors indicate that DRD must be taken into account in differential diagnosis of movement disorders in children, mostly in progressive cases. Good effect of L-Dopa treatment is one of the basic phenomena helpful in DRD recognition. PMID- 17338137 TI - [The case of 57-year-old patient with ornithosis]. AB - The authors describe the case of ornithosis in the form of severe pleuropneumonia with breathing disorders. They emphasize that the proper diagnosis and consequently the treatment have been achieved by the detailed anamnesis and not by additional tests, as the immune reaction was found after full remission of pathological lesions. PMID- 17338138 TI - Unusual case of mixed sclerosing bone dysplasia in a 3.5-year-old boy. AB - The aim of the study is a description of a 3.5-year-old boy with mixed sclerosing bone dysplasia. From boy's birth the shortening of the left upper limb and malfunction of the left elbow joint were observed. Physical examination showed: higher placement of the left shoulder, obligatory outside-rotation position of the left lower limb, mobility limitation of the left: elbow, hip and knee joints. Examinations--including calcium-phosphatic, ionic and hormone metabolism--were normal. Roentgenograms and computer tomography (CT) examination showed a picture typical for melorheostosis in upper left limb and changes typical for osteopathia striata in left hip and left femoral bones. Scintigraphy showed bilateral bigger radiomarker uptake in the left femoral bone and in right humerus, femoral bone and tibia. The above described case is a mixed sclerosing bone dysplasia- coexisting of melorheostosis and osteopathia striata. PMID- 17338139 TI - [Diagnostic difficulties in diffuse pulmonary infiltrations]. AB - We described a case of 26-year-old woman, with the history of cough and exercise dyspnoea. Chest X-ray and HRCT examination showed diffuse interstitial infiltration. Histopathological examination of supraclavicular lymph nodes and lung tissue obtained by transbronchial biopsy revealed metastatic adenocarcinoma. Despite several examinations, including gastroscopy- the primary site of cancer was not established. Rapid progression of the disease led to death. Post-mortem examination revealed diffuse gastric carcinoma as the primary neoplasm. PMID- 17338140 TI - [Linezolid--novel antibiotic for the treatment of gram-positive bacterial infections]. AB - Linezolid, the first of a new class of antibiotics, the oxazolidinones, is approved for the treatment of Gram-positive bacterial infections, including resistant strains. Linezolid possesses bacteriostatic activity against both antibiotic-susceptible and resistant strains of staphylococci, enterococci and streptococci of relevance to human infection. Clinical trials have confirmed its effectiveness in the treatment of serious infections of skin and soft tissue and the lower respiratory tract. Linezolid has also provided improved outcomes in the treatment of serious vancomycin-resistant entrococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA) infections. It is well absorbed with high bioavailability after oral administration and generally well tolerated. PMID- 17338141 TI - [Tissue engineering yesterday and today. Part II]. AB - Science and technology is always an important component of human culture. Science directs technological innovation and technology accelerates the progress of science. Increasing number of achievements in tissue engineering domain make possible ex vivo maintaining not only the isolated cells, but also tissues and organs. Tissue engineering powerfully expanding from over hundred years, contribute to the development of genetics, transplantology, oncological diagnostics, pharmacology, toxicology and many other medical sciences. Presented paper summarizes the scientists' accomplishments in the field of tissue engineering which were noted in the second half of twentieth century. PMID- 17338142 TI - Heaves, genes, nerves, and Victorians. PMID- 17338143 TI - Clinicopathologic features and outcome predictors of Leptospira interrogans Australis serogroup infection in dogs: a retrospective study of 20 cases (2001 2004). AB - BACKGROUND AND HYPOTHESIS: We retrospectively evaluated the clinicopathologic findings and outcome predictors in dogs with Leptospira interrogans Australis serogroup infections. ANIMALS AND METHODS: The medical records of 159 dogs that had a leptospiral microscopic agglutination test (MAT) performed between 2001 and 2004 were reviewed. RESULTS: Twenty dogs met serologic criteria for either symptomatic (16 dogs) or asymptomatic (4 dogs) infection caused by Leptospira interrogans Australis serogroup. Seven of 16 symptomatic dogs died or were euthanized and 9/16 recovered. Systemic inflammatory response syndrome (SIRS) was observed in 9/16 dogs. The presence of SIRS did not affect prognosis (P = .357). C-reactive protein (CRP) and haptoglobin (Hpt) concentrations were altered in all symptomatic dogs, but results did not differ significantly between survivors and nonsurvivors (P = .08 and P = .055, respectively). Conversely, the CRP to Hpt ratio (CRP/Hpt) was significantly increased in nonsurvivors. Disseminated intravascular coagulation (DIC) was diagnosed in 7/16 dogs. DIC did not significantly affect outcome (P = .126). Multiple organ involvement was present with renal failure in 16/16, liver damage in 12/16, cardiac damage in 11/16, and muscular damage in 8/16 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Among the evaluated clinicopathologic biomarkers, serum albumin, cardiac troponin I, CRP/Hpt, urinary albumin, and urinary total protein to creatinine ratio were found to predict outcome and warrant evaluation in larger prospective studies. PMID- 17338144 TI - Evaluation of clinical, macroscopic, and histopathologic response to treatment in nonhypoproteinemic dogs with lymphocytic-plasmacytic enteritis. AB - BACKGROUND: Lymphocytic-plasmacytic enteritis (LPE) is a common cause of chronic vomiting and diarrhea in dogs. However, little information is available about endoscopic or histopathologic improvement after therapy in dogs with LPE. HYPOTHESIS: The objective was to study the clinical, endoscopic, and histopathologic evolution of LPE during and after immunosuppressive treatment with prednisone and metronidazole. Most dogs also were treated symptomatically with metoclopramide and cimetidine. ANIMALS: Sixteen dogs with LPE and normal serum protein concentrations diagnosed at the Veterinary Medical Teaching Hospital of the Complutense University of Madrid were monitored during and after drug treatment. The control group consisted of 9 dogs that had no gastrointestinal signs for the preceding 12 months. METHODS: In this prospective clinical treatment trial, clinical, endoscopic, and histopathologic scores were evaluated to describe disease evolution during conventional therapy. Dogs with LPE were monitored for 120 days from the start of treatment. Re-evaluation was performed on post-treatment days 30, 60, 90 (end of treatment), and 120. RESULTS: The average disease activity index observed in our study fell progressively from its initial value, and the decrease between consecutive re-evaluations was statistically significant until day 60 (P = .04). Our results indicate that 75% of the animals revealed improvement of endoscopic gastric lesions (defined as a reduction of the endoscopic score) after treatment, and 75% exhibited improvement of endoscopic duodenal lesions. Statistical analysis of the data revealed significant differences between pre- and post-treatment gastric and duodenal macroscopic endoscopic lesions (P < .05). On the other hand, treatment did not lead to any significant changes in the severity of the gastric and duodenal histopathologic lesions of the affected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Treatment of nonhypoproteinemic dogs with LPE led to clinical and endoscopic improvement, but histopathologic lesions were unchanged during therapy. PMID- 17338145 TI - Percutaneous endoscopic gastrojejunostomy tube placement in healthy dogs and cats. AB - BACKGROUND: Pancreatitis, hepatobiliary disease, and proximal gastrointestinal tract disorders are clinical situations where delivery of nutrients via jejunostomy tube is preferable to a feeding gastrostomy. A thorough description of the percutaneous endoscopic gastrojejunostomy (PEG-J) technique and practical guidelines for its use in small animals have not been reported. HYPOTHESIS: That a simple technique of PEG-J tube placement in humans would be useful and safe in healthy dogs and cats. ANIMALS: Twelve healthy dogs and 5 healthy cats were included in the study. MATERIALS AND METHODS: Commercially prepared PEG-J tubes were modified for use in animals and positioned in the small intestine by endoscopic guidance. Eight dogs and 5 cats were bolus fed enteral diets for 14 days. Complications associated with the use of the PEG-J tube and responses to bolus feedings were assessed. RESULTS: Jejunostomy tubes were placed distal to the caudal duodenal flexure in all dogs and cats. Complications associated with PEG-J tubes occurred in 5/12 dogs and 4/5 cats and included J-tube removal, local pain/inflammation, retrograde tube migration, and diarrhea. Bolus feeding (daily maintenance energy requirement [MER] divided q8h) through the jejunostomy catheter was well tolerated, maintained normal body weight, and was not associated with adverse gastrointestinal signs. CONCLUSIONS AND CLINICAL IMPORTANCE: Placement of a PEG-J tube is an effective, noninvasive technique for providing enteral nutritional support of healthy dogs and cats. Bolus-feeding techniques via PEG-J tubes maintain normal nutritional status in healthy dogs and cats. This procedure for jejunostomy feeding may be easily adapted for use in clinical practice outside of an intensive care facility. PMID- 17338146 TI - Assessment of thyroid function in dogs with low plasma thyroxine concentration. AB - BACKGROUND: Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. HYPOTHESIS: The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. ANIMALS: In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. METHODS: The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. RESULTS: Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness. PMID- 17338147 TI - Chronic hepatitis in Labrador Retrievers: clinical presentation and prognostic factors. AB - BACKGROUND: An increased incidence of chronic hepatitis has been reported in Labrador Retrievers. HYPOTHESIS: A breed associated hepatopathy occurs in Labrador Retrievers. ANIMALS: Twenty-four client-owned Labrador Retrievers. METHODS: Medical records of dogs with histopathologic confirmation of chronic hepatitis were retrospectively reviewed. A clinical score based on clinical signs and the results of biochemical tests was generated for each dog. Hepatic biopsy specimens were scored for disease activity, fibrosis, and copper accumulation. RESULTS: The median age was 9.3 years (range, 3.9-14.0 years). Clinical signs included inappetence, vomiting, lethargy, and weight loss. All dogs had increases in serum activity of one or more hepatobiliary enzyme. Hyperbilirubinemia and hypoalbuminemia were present in 45% and 21% of dogs, respectively. The median clinical score was 2.9, with a range of 0-8. The median histopathology activity and the fibrosis scores were 3.5 (range, 1-6) and 3.0 (range, 0-4), respectively. Rhodanine-positive copper staining was present in 15 of 17 biopsy specimens, with a median score of 2.0 (range, 0-3). Median survival was 374 days (range, 1-2645 days). A prolonged prothrombin time (P = .013) and thrombocytopenia (P = .041) were associated with survival < 2 months. The presence of anorexia (P = .049), hypoglobulinemia (P = .045), or prolonged partial thromboplastin time (P = .033) were associated with shorter overall survival times. The clinical score correlated with survival time (P = .030) and histopathologic staging (P = .049). CONCLUSIONS AND CLINICAL IMPORTANCE: A progressive hepatopathy in Labrador Retrievers in this study was marked by chronic inflammation, fibrosis, and copper accumulation. A clinical scoring system that correlates with survival time may be useful as a noninvasive method to predict prognosis. PMID- 17338148 TI - Glycogen storage disease type IIIa in curly-coated retrievers. AB - BACKGROUND: Inborn errors of metabolism impose a significant genetic burden on purebred dogs and cats. The glycogen storage diseases are a category of such disorders that are typed by enzyme analysis, but deoxyribonucleic acid (DNA) based carrier tests are needed for definitive, noninvasive diagnosis and to prevent at-risk matings. HYPOTHESIS: Glycogen storage disease type IIIa (GSD IIIa) is caused by a mutation of the glycogen debranching enzyme gene (AGL) in Curly-Coated Retrievers (CCR). ANIMALS: Two CCR exhibiting episodic exercise intolerance, collapse, and lethargy, and related dogs were studied. METHODS: Structure and amount of glycogen isolated from tissue biopsy specimens was determined by enzymatic digestion, and activities of enzymes of glycogen metabolism were measured. The 33 AGL coding exons and flanking splice sites of an affected dog were amplified by polymerase chain reaction and sequenced. RESULTS: Debranching enzyme activity was undetectable in liver and skeletal muscle of affected dogs, and accumulated glycogen had absent or short outer chains of alpha1, 4-linked glucose. A single adenosine (A) deletion in AGL exon 32 of affected dog genomic DNA predicted a frame-shift and truncation of the protein product by 126 amino acid residues. The mutation was homozygous in affected dogs and heterozygous in both parents. In addition, the deletion mutation was heterozygous in 16 or not detected at all in 31 related but clinically normal CCR. CONCLUSIONS AND CLINICAL IMPORTANCE: GSD IIIa in CCR is an autosomal recessive trait caused by mutation of AGL. A DNA sequence-based carrier test was developed, and carriers were identified in the United States, New Zealand, Australia, and Finland. PMID- 17338149 TI - Effect of phenylpropanolamine and pseudoephedrine on the urethral pressure profile and continence scores of incontinent female dogs. AB - BACKGROUND: Traditionally, treatment of urinary incontinence in spayed female dogs has been to increase urethral sphincter tone with estrogen compounds or alpha-agonists. Phenylpropanolamine (PPA) is the most frequently used alpha agonist for this condition, but increased cost and decreased availability of PPA as an over-the-counter medication have prompted interest in alternative therapies that may provide the same degree of efficacy. Pseudoephedrine (PD), an alpha agonist and stereoisomer of ephedrine, is more cost-effective and available without a prescription. HYPOTHESIS: PD will not differ from PPA in its effects on urodynamic variables and owner-reported continence scores or in observed adverse effects. ANIMALS: Nine spayed female dogs with a history of urinary incontinence drawn from the clinical patient population at the Veterinary Teaching Hospital at The Ohio State University. METHODS: A randomized, double-blind crossover study evaluating changes in urodynamic variables, owner-reported continence score, and adverse effects in dogs treated with 1.5 mg/kg PO q8h PPA or PD. RESULTS: Changes in maximum urethral closure pressure and functional area after PPA therapy were significantly higher than after PD therapy. There was no change in the functional profile length after either treatment. There was a significant increase in the continence score after PPA therapy, but not after PD therapy. More adverse effects were observed in dogs treated with PD than with PPA. CONCLUSIONS AND CLINICAL IMPORTANCE: Although some dogs clinically improved, lack of statistically significant changes in urodynamic variables and owner perception of continence as well as the increased incidence of adverse effects make PD a less satisfactory alternative to PPA for the treatment of urinary incontinence in female dogs. PMID- 17338150 TI - Prognostic factors in canine exocrine pancreatic insufficiency: prolonged survival is likely if clinical remission is achieved. AB - BACKGROUND: Response to therapy in canine exocrine pancreatic insufficiency (EPI) varies considerably, making it difficult to determine prognosis for individual patients. HYPOTHESIS: Response to initial treatment (RIT) and survival are affected by signalment, clinical variables, and therapeutic regimen employed. ANIMALS: Client-owned dogs diagnosed with EPI between 1990 and 2002 were included in this study. METHODS: The study comprised a retrospective, questionnaire-based review. RESULTS: One hundred seventy-eight completed questionnaires were returned. RIT was good in 60% of treated dogs, partial in 17%, and poor in 23%. On univariate analysis, dogs that received antibiotics (P = .037) or had high serum folate concentration (P = .037) had a poorer RIT. On multivariate analysis, there were no strong predictors of good RIT. Nineteen percent of treated dogs were euthanized within 1 year, but overall median survival time for treated dogs was 1919 days. No clear benefit of changing to a fat-restricted diet could be demonstrated, but marked hypocobalaminemia (< 100 ng/L) was associated with shorter survival (P = .012). Use of uncoated pancreatic enzyme supplements, antibacterials, or H2 antagonists was not associated with longer survival. Breed, sex, age at diagnosis ( < or = 4 years or > 4 years), and clinical signs at diagnosis also made no difference. CONCLUSIONS AND CLINICAL IMPORTANCE: Long-term prognosis in canine EPI is favorable for dogs that survive the initial treatment period. Although there are few predictors of good RIT or long-term survival, severe cobalamin deficiency is associated with shorter survival. Therefore, parenteral cobalamin supplementation should be considered when hypocobalaminemia is documented. PMID- 17338151 TI - Decreased systolic function and inadequate hypertrophy in large and small breed dogs with chronic mitral valve insufficiency. AB - BACKGROUND: Systolic dysfunction associated with chronic mitral valve insufficiency (CMVI) has been demonstrated in experimental animal models and large breed (LB) dogs but has been reported as an uncommon finding in small breed (SB) dogs with naturally occurring disease. It has been suggested the myocardial failure could be, in part, because of an insufficient increase in left ventricular mass. HYPOTHESIS: To test if SB and LB dogs with CMVI and moderate heart failure have systolic dysfunction and if they have adequate eccentric hypertrophy. ANIMALS: Data from 38 SB and 18 LB dogs affected with CMVI were compared retrospectively with results from 2 groups of normal dogs (17 SB and 32 LB). METHODS: Systolic function was investigated echocardiographically by using percentage fractional shortening (FS), the ratio between observed and expected end-systolic diameter (ESD/ESDe), and end-systolic volume index (ESVI). Left ventricular hypertrophy was estimated by using the ratio between the thickness of the left ventricular free wall and the radius in diastole (h/R). RESULTS: Both affected SB and LB dogs had a significantly increased FS and ESVI (FS% SB 45.6 + 8.04 versus 40.06 + 8.9, P < .05; FS% LB 33.64 + 8.61 versus 27.3 + 7.3 P < .05; ESVI SB 30.0 +/- 2.3 mL/m2 versus 21.18 +/- 13.9 mL/m2, P < .05; ESVI LB 83.22 +/ 43.84 mL/m2 versus 36.43 +/- 13.30 mL/m2 versus P < .001). The h/R in affected animals was decreased (0.53 +/- 0.11 versus 0.41 +/- 0.12, P < .05 SB; 0.47 +/- 0.11 versus 0.38 +/- 0.09, P < .05, LB). CONCLUSIONS AND CLINICAL IMPORTANCE: Data from this study indicate that dogs with moderate heart failure caused by CMVI have systolic dysfunction. Inadequate hypertrophy of the left ventricle may be, in part, responsible for this finding. PMID- 17338152 TI - Echocardiographic and angiographic comparison of ductal dimensions in dogs with patent ductus arteriosus. AB - BACKGROUND: Transcatheter occlusion of patent ductus arteriosus (PDA) is a minimally invasive treatment option in dogs. Device selection based on appropriately acquired PDA dimensions and morphology can minimize procedural complications, including minimizing residual ductal flow and inappropriate embolization. HYPOTHESIS: Transesophageal echocardiographic (TEE) derived minimum ductal diameter measurements would most accurately reflect angiographic measurements. Color Doppler (CD) TEE and transthoracic echocardiographic (TTE) ductal measurements would overestimate two-dimensional (2D) measurements. ANIMALS: Fifteen client-owned dogs with PDA. METHODS: PDA dimensions obtained with angiography, 2D and CD TTE, 2D and CD TEE from the right and left views were prospectively evaluated. RESULTS: PDA dimensions were measured by using TEE most closely approximated angiographic measures. CD TTE and TEE frequently overestimated angiographic measures of minimum ductal diameter. TEE accurately identified a type III (tubular) PDA morphology in 1 dog. Fourteen of 15 dogs were determined to have hemodynamically significant reductions in left to right shunting documented by a first-pass nuclear angiocardiographic ratio of pulmonary to systemic blood flow < or = 1.2 and trivial (n = 3) to no (n = 11) CD TTE flow at approximately 1 month after PDA occlusion. CONCLUSIONS: TEE provided accurate anatomic information regarding PDA morphology and closely approximated angiographic ductal dimensions while aiding in both coil deployment and confirmation of intra-operative ductal closure. PMID- 17338153 TI - Double chambered right ventricle in 9 cats. AB - BACKGROUND: Double-chambered right ventricle (DCRV) is a frequently recognized cardiac congenital abnormality in humans. It has been described in dogs and in 1 cat. However systemic description of clinical and echocardiographic features of the disease in cats is currently lacking from the veterinary literature. ANIMALS: Nine cats with DCRV are described. RESULTS: The cats ranged from 4 months to 10 years of age. Eight cats at presentation were asymptomatic and 1 cat had chylothorax. In all cases echocardiography revealed abnormal fibromuscular bundles obstructing the mid-right ventricle, dividing the chamber into 2 compartments. The proximal right ventricular compartment was markedly hypertrophied, and right atrial dilation was usually present. The mean pressure gradient measured across the stenotic area was 130 +/- 50 mm Hg. Concurrent abnormalities included a ventricular septal defect (n = 2); aortic malalignment, aortic insufficiency (n = 1); and congenital peritoneal-pericardial diaphragmatic hernia (n = 1). Two cats had systolic anterior motion of the mitral valve, one of which had concurrent left ventricular hypertrophy. Five cats have remained asymptomatic for a median period of 3.6 years (range, 3.3-5 years) and 3 cats have developed clinical signs associated with congestive heart failure (at 2, 3.3, and 9 years). One cat showed progressive lethargy and exercise intolerance and underwent partial ventriculectomy at the age of 2 years. This cat died during the operation with electromechanical dissociation. CONCLUSIONS: DCRV is a congenital cardiac abnormality that may be more common than previously recognized. PMID- 17338154 TI - Assessment of diastolic function by Doppler echocardiography in normal Doberman Pinschers and Doberman Pinschers with dilated cardiomyopathy. AB - BACKGROUND: Assessment of diastolic function in patients with dilated cardiomyopathy (DCM) has the potential to add valuable information regarding hemodynamics, disease severity, and prognosis. The purpose of this study was to determine transmitral flow (TMF), isovolumic relaxation time (IVRT), pulmonary venous flow (PVF), flow propagation velocity (Vp), and mitral annular velocities by tissue Doppler in Doberman Pinschers with and without DCM. HYPOTHESIS: It was anticipated that normal and DCM Dobermans would differ with respect to these parameters, and that associations with time to congestive heart failure (CHF) or death would be found. ANIMALS: Thirty client-owned Doberman Pinschers (10 each of normal, occult DCM, and overt DCM) were studied. METHODS: Each dog underwent echocardiography with or without thoracic radiography (to confirm CHF) for classification as normal or DCM-affected, followed by collection of echocardiographic diastolic parameters. RESULTS: The group with occult DCM exhibited features of pseudonormal TMF, reduced systolic to diastolic PVF ratio, and reduced Vp. Shorter early TMF deceleration time (DTE) was associated with shorter time to CHF or sudden death. The group with overt DCM exhibited restrictive TMF, blunted systolic PVF, and reduced early and late diastolic mitral annular velocities. CONCLUSIONS AND CLINICAL IMPORTANCE: Doberman Pinschers showed evidence of moderate and severe diastolic dysfunction in occult and overt DCM, respectively. Short DTE may be a useful predictor of onset of CHF or sudden death. PMID- 17338155 TI - Plasma big endothelin-1, atrial natriuretic peptide, aldosterone, and norepinephrine concentrations in normal Doberman Pinschers and Doberman Pinschers with dilated cardiomyopathy. AB - BACKGROUND: Dilated cardiomyopathy (DCM) results in progressive myocardial and circulatory dysfunction causing activation of a number of neurohormonal systems, including the endothelin (ET) system, which is only beginning to be described in clinical veterinary medicine. Measurement of these circulating neurohormones possesses potential utility in the diagnosis, staging, and assessment of prognosis in cardiac disease. HYPOTHESIS: We hypothesized that plasma big ET-1, norepinephrine (NE), aldosterone, and atrial natriuretic peptide (ANP) concentrations in normal Dobermans would differ from those in Dobermans with DCM, and that concentrations of these hormones would be associated with time to congestive heart failure (CHF) or death. ANIMALS: Thirty client-owned Dobermans (10 each of normal, occult DCM, and overt DCM) were included in the study. METHODS: Dogs underwent an echocardiogram, ECG, and blood sample collection. Neurohormones were measured by high-pressure liquid chromatography (NE) or commercial assays. RESULTS: Dogs with occult DCM had significantly higher ANP concentrations compared with normal dogs (least squares means [95% confidence interval, CI]: occult female 53.7 pg/mL [40.2-71.7] versus normal female 31.6 pg/mL [24.8-40.3], P = .026; occult male 86.1 pg/mL [64.7-115] versus normal male 12.1 pg/mL [5.1-28.7], P = .011). Dogs with overt DCM had significantly higher concentrations of all neurohormones compared with the normal group. Furthermore, increasing big ET-1 (risk ratio [RR] 2.7, CI 1.3-8.6, P = .01) and NE concentrations (RR 3.9, CI 1.1-18.1, P = .03) over 1 month were associated with a shorter survival time. CONCLUSIONS AND CLINICAL IMPORTANCE: High ANP concentrations can identify dogs with advanced occult DCM. Increasing big ET-1 or NE concentrations over time can be useful predictors of poor prognosis. PMID- 17338156 TI - Procarbazine as adjunctive therapy for treatment of dogs with presumptive antemortem diagnosis of granulomatous meningoencephalomyelitis: 21 cases (1998 2004). AB - BACKGROUND: Granulomatous meningoencephalomyelitis (GME) is an idiopathic inflammatory disease of the central nervous system. Remission often is short lived in dogs treated with glucocorticoids. Procarbazine is T cell-specific and crosses the blood-brain barrier. HYPOTHESIS: Dogs with presumptive antemortem diagnosis of GME given procarbazine as adjunctive therapy to prednisone will have improved long-term outcome compared with dogs given no treatment or glucocorticoids alone. ANIMALS: Two groups were studied: (1) Dogs with presumptive antemortem diagnosis of GME treated with procarbazine and prednisone (n = 21); (2) Dogs that had a histologic diagnosis of GME at postmortem examination and received no treatment (n = 11). METHODS: Dogs with presumptive GME treated with procarbazine were identified retrospectively from medical records of 2 veterinary referral hospitals. Selection criteria required all dogs have a neurologic examination, blood work, cerebrospinal fluid analysis, and brain imaging (MRI or CT). RESULTS: Median survival time for all dogs studied was 5.0 months. Median survival time for dogs treated with procarbazine was 14.0 months and for untreated dogs, 0.73 months. Treatment with procarbazine was significantly correlated with survival time (P < .001). Procarbazine was the only independent predictor of survival. Prednisone was reduced in dosage or discontinued in 17 dogs. Adverse reactions to procarbazine therapy included myelosuppression in 7 dogs and hemorrhagic gastroenteritis in 3 dogs. CONCLUSION: These data suggest that procarbazine treatment of presumptive GME may result in greater improved long-term outcome than has been previously reported for glucocorticoid treatment alone and may complement other immunomodulatory therapies. Procarbazine-treated dogs must be monitored for adverse reactions. PMID- 17338157 TI - Platelet concentrations and platelet-associated IgG in greyhounds. AB - BACKGROUND: Greyhounds have lower platelet concentrations (PC) than dogs of other breeds have. No underlying cause has been investigated. HYPOTHESIS: We hypothesized that Greyhounds have lower mean PC because of breed variation, not immune-mediated causes. Our secondary hypothesis was that PC is dependent on the method of analysis. ANIMALS: Sixty privately owned Greyhounds in Kansas. METHODS: Blood samples were collected into evacuated glass tubes containing ethylenediamine tetraacetic acid (EDTA). Blood smears were evaluated for platelet clumps. All 60 samples had PC determined by manual, impedance, and buffy coat analyzer methods. Results of the 60 samples were compared with results of samples with (n = 25) and without (n = 35) clumps, and with control dogs. Platelets were assayed for the presence of surface-associated antigen (PSAIgG) by direct immunofluorescence. RESULTS: The mean PC was below that of the control dogs for the impedance method (P < .001). No significant difference in PC was detected between analysis methods or between samples with or without platelet clumps. Three of 60 (5%) of the Greyhounds had PC between 50,000 and 100,000/microL with impedance analysis; no samples had < 100,000/microL via buffy coat analysis. PSAIgG was not identified in any samples. CONCLUSIONS AND CLINICAL IMPORTANCE: The mean Greyhound PC for the impedance method was below the reference interval for control dogs but was not significantly different from PC determined by other methods. An immune-mediated cause for the lower PC was unlikely because no samples had PSAIgG. The decreased PC is most consistent with breed variation. As only 0-5% of samples, depending on analysis method, had PC < 100,000/microL, a Greyhound with a PC < 100,000/microL is not necessarily consistent with breed variation, thus diagnostic testing is indicated. PMID- 17338158 TI - Evaluation of a novel tumor vaccine in dogs with hemangiosarcoma. AB - BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor of dogs. At present, adjuvant chemotherapy is the only proven effective treatment for dogs with HSA, though the benefits from chemotherapy are modest. Administration of immunotherapy together with chemotherapy has also been reported to improve survival in dogs with HSA. Therefore, we evaluated safety and immunologic responses to a novel tumor vaccine administered together with doxorubicin chemotherapy in dogs with different stages of HSA. HYPOTHESIS: That tumor vaccination could be safely and effectively combined with doxorubicin chemotherapy for treatment of dogs with HSA. ANIMALS: Twenty-eight dogs with various stages of HSA were enrolled in the study. METHODS: The HSA vaccine was prepared with lysates of allogeneic canine HSA cell lines mixed with an adjuvant composed of liposome-DNA complexes. Dogs received a series of 8 immunizations administered over a 22-week period, and most also received chemotherapy. Clinical adverse effects were noted, immune responses were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and survival times were calculated. RESULTS: The most common adverse effects observed in vaccinated dogs also treated with doxorubicin chemotherapy were diarrhea and anorexia. Vaccinated dogs were found to mount strong humoral immune responses against a control antigen and, most dogs also mounted antibody responses against canine HSA cells. Thirteen dogs with stage II splenic HSA that received the tumor vaccine plus doxorubicin chemotherapy had an overall median survival time of 182 days. CONCLUSIONS: We conclude that an allogeneic tumor lysate vaccine is safe in dogs with HSA and can elicit humoral immune responses in dogs that are receiving concurrent doxorubicin chemotherapy. PMID- 17338160 TI - Combination chemotherapy with L-asparaginase, lomustine, and prednisone for relapsed or refractory canine lymphoma. AB - BACKGROUND: Canine lymphoma (LSA) is responsive to initial treatment, however, it then becomes resistant to drugs in the initial protocol. New rescue protocols are needed. HYPOTHESIS: A combination of L-asparaginase, lomustine, and prednisone will be well tolerated and efficacious as a rescue therapy for dogs with LSA. ANIMALS: Thirty-one client owned dogs with cytologically confirmed multicentric LSA who were refractory or whose disease had relapsed after a CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)-based chemotherapy protocol. METHODS: Prospective clinical trial. Lomustine (target dose, 70 mg/m2) was administered orally at 3-week intervals for a total of 5 doses or until disease progression. L-asparaginase (400 U/kg) was administered subcutaneously concurrently with the first 2 lomustine treatments. Prednisone was administered at a tapering dose for the duration of the protocol. RESULTS: Overall response rate for dogs treated with this protocol was 87% (27/31), with 52% (16/31) of dogs achieving a complete response. Median time to response was 21 days. Median time to progression was 63 days (111 days for dogs achieving a complete response and 42 days for dogs achieving a partial response). There were no significant differences in response rates and times to progression between dogs who had received L-asparaginase before beginning this rescue protocol and those who had not. Toxicoses were mild and self-limiting in 29 of 31 cases. CONCLUSIONS AND CLINICAL IMPORTANCE: This is a well-tolerated rescue therapy for relapsing LSA in dogs. Response rates and remission durations compare favorably to other rescue protocols. Therefore, this protocol is a viable rescue option. PMID- 17338159 TI - CCNU for the treatment of dogs with histiocytic sarcoma. AB - BACKGROUND: Histiocytic sarcoma is an aggressive neoplasm of dendritic cells that carries a grave prognosis. The efficacy of chemotherapy against this disease is unknown. The purpose of this study was to determine the efficacy of 1-(2 chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in dogs with incompletely resected or metastatic histiocytic sarcoma, to describe the clinical characteristics of these dogs, and to identify factors affecting prognosis. HYPOTHESIS: Our hypothesis is that CCNU has activity against canine histiocytic sarcoma and can improve survival in dogs with advanced disease. ANIMALS: Included in analysis are dogs diagnosed with histiocytic sarcoma who had gross measurable or residual microscopic disease and who received CCNU. METHODS: A multi-institutional, retrospective, single-arm cohort study was conducted. Available biopsy samples were tested with an antibody against CD18 when possible to confirm the diagnosis of histiocytic sarcoma. RESULTS: Fifty-nine dogs were treated at 8 institutions. Twenty-three tumor specimens were confirmed to be CD18 positive. Treatment with CCNU at 60 to 90 mg/m2 resulted in an overall response rate of 46% in the 56 dogs with gross measurable disease. All 3 dogs with minimal residual disease experienced tumor relapse but lived 433 days or more after starting CCNU. The median survival of all 59 dogs was 106 days. Thrombocytopenia (< 100,000 platelets/microL) and hypoalbuminemia were found to be negatively associated with prognosis and were predictive of < 1 month survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that CCNU is active against canine histiocytic sarcoma and may be useful in the treatment of dogs without negative prognostic factors. PMID- 17338161 TI - Expression of receptor activator of nuclear factor kappa-B ligand (RANKL) in neoplasms of dogs and cats. AB - BACKGROUND: Receptor activator of nuclear factor kappa-B (RANK), RANK-ligand (RANKL), and the soluble decoy receptor osteoprotegerin (OPG) form a key axis modulating osteoclastogenesis. In health, RANKL-expressing bone stromal cells and osteoblasts activate osteoclasts through RANK ligation, resulting in homeostatic bone resorption. Skeletal tumors of dogs and cats, whether primary or metastatic, may express RANKL and directly induce malignant osteolysis. HYPOTHESIS: Bone malignancies of dogs and cats may express RANKL, thereby contributing to pathologic bone resorption and pain. Furthermore, relative RANKL expression in bone tumors may correlate with radiographic characteristics of bone pathology. ANIMALS: Forty-two dogs and 6 cats with spontaneously-occurring tumors involving bones or soft tissues were evaluated. METHODS: A polyclonal anti-human RANKL antibody was validated for use in canine and feline cells by flow cytometry and immunocytochemistry. Fifty cytologic specimens were collected from bone and soft tissue tumors of 48 tumor-bearing animals and assessed for RANKL expression. In 15 canine osteosarcoma (OSA) samples, relative RANKL expression was correlated with radiographic characteristics of bone pathology. RESULTS: Expression of RANKL by neoplastic cells was identified in 32/44 canine and 5/6 feline tumor samples. In 15 dogs with OSA, relative RANKL expression did not correlate with either radiographic osteolysis or bone mineral density as assessed by dual energy x-ray absorptiometry. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs and cats, tumors classically involving bone and causing pain, often may express RANKL. Confirming RANKL expression in tumors is a necessary step toward the rational institution of novel therapies targeting malignant osteolysis via RANKL antagonism. PMID- 17338162 TI - Prophylactic trimethoprim-sulfadiazine during chemotherapy in dogs with lymphoma and osteosarcoma: a double-blind, placebo-controlled study. AB - BACKGROUND: The administration of chemotherapy is associated with risk for morbidity. Management of chemotherapy-related morbidity in veterinary oncology has been primarily supportive. HYPOTHESIS: The purpose of this study was to evaluate the effect of prophylactic antimicrobial use on chemotherapy-associated morbidity in dogs with lymphoma or osteosarcoma. ANIMALS: Dogs presenting with histologically confirmed osteosarcoma or lymphoma were eligible. METHODS: Patients were randomized to receive placebo or trimethoprim-sulfadiazine for 14 days after their first doxorubicin chemotherapy. Both owner and clinician were blinded with respect to treatment. Patient assessment included CBC, physical examination and performance, and toxicosis grading on days 7 and 14. Investigated outcomes were hospitalization, suspicion of infection, gastrointestinal toxicity, neutropenia, nonhematologic toxicity, and quality of life. RESULTS: Seventy-three dogs were enrolled; 34 had osteosarcoma, and 39 had lymphoma. Dogs receiving trimethoprim-sulfadiazine (n = 36) had a significantly reduced hospitalization rate (P = .03), nonhematologic toxicity (P = 0.039), grade 2-4 nonhematologic toxicity (P < .0001), grade 2-4 gastrointestinal toxicity (P = .007). and altered performance (P = .015). By group, dogs with osteosarcoma (n = 34) that received the antimicrobial experienced fewer occurrences of nonhematologic toxicity (P = .02) and less severe nonhematologic toxicity (P = .038). Dogs with lymphoma (n = 39) had significant reductions in the occurrence of hospitalization (P = .035), severity of nonhematologic toxicity (P = .036), and alterations of performance (P = .015). CONCLUSIONS: The use of prophylactic trimethoprim-sulfadiazine has benefit in reducing morbidity in dogs with osteosarcoma or lymphoma during the first 14 days after treatment with doxorubicin. PMID- 17338163 TI - Effects of genetic and environmental factors on chronic lower airway disease in horses. AB - BACKGROUND: Environment and genetics influence the manifestation of recurrent airway obstruction (RAO), but the associations of specific factors with mild, moderate, and severe clinical signs are unknown. HYPOTHESIS: We hypothesized that sire, feed, bedding, time outdoors, sex, and age are associated with clinical manifestations of mild, moderate, and severe lower airway disease. ANIMALS: Direct offspring of 2 RAO-affected Warmblood stallions (F1S1, n = 172; F1S2, n = 135); maternal half-siblings of F1S1 (mHSS1, n = 66); and an age-matched, randomly chosen control group (CG, n = 33). METHODS: A standardized questionnaire was used to assess potential risk factors and to establish a horse owner assessed respiratory signs index (HOARSI 1-4, from healthy to severe) according to clinical signs of lower airway disease. RESULTS: More F1S1 and F1S2 horses showed moderate to severe clinical signs (HOARSI 3 and HOARSI 4 combined, 29.6 and 27.3%, respectively) compared with CG and mHSS1 horses (9.1 and 6.2%, respectively; contingency table overall test, P < .001). Sire, hay feeding, and age (in decreasing order of strength) were associated with more severe clinical signs (higher HOARSI), more frequent coughing, and nasal discharge. CONCLUSIONS AND CLINICAL RELEVANCE: There is a genetic predisposition and lesser but also marked effects of hay feeding and age on the manifestation of moderate to severe clinical signs, most markedly on coughing frequency. In contrast, mild clinical signs were not associated with sire or hay feeding in our populations. PMID- 17338164 TI - Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center. AB - BACKGROUND: Equine herpesvirus type 1 (EHV-1) infection causes neurologic disease in horses. However, risk factors for the disease and long-term prognosis are poorly characterized. HYPOTHESIS: There are identifiable risk factors for equine herpes-1 myeloencephalopathy. ANIMALS: The entire population of 135 horses housed within the equestrian facility. METHODS: A descriptive study investigated the clinical, serologic, virologic, and management aspects of an outbreak of EHV-1 myeloencephalopathy. RESULTS: Out of 135 horses at the facility, 117 displayed signs of EHV-1 infection. Forty-six horses developed neurologic deficits characterized by symmetrical hind limb ataxia and weakness. Twelve horses that developed neurologic deficits became recumbent and did not survive. The development of severe neurologic deficits during the outbreak was associated with the presence of residual deficits at the 6-month examination. Within 1 year of the outbreak onset, all horses that survived had returned to an exercise level comparable to that experienced before the outbreak. Factors associated with the development of neurologic disease included age of > 5 years, location in the south or arena stall areas, and highest rectal temperature on day 3 or later of the febrile period. CONCLUSIONS AND CLINICAL IMPORTANCE: Being > 5 years of age, having had a rectal temperature of > 103.5 degrees F, and highest rectal temperature occurring on or after the 3rd day of the febrile period were the factors most predictive of the development of neurologic disease and death. Data obtained during this outbreak substantiate previous findings relating to clinical aspects and diagnosis of EHV-1 myeloencephalopathy. The prophylactic and therapeutic use of acyclovir during this outbreak is described. PMID- 17338165 TI - Atrial, SA nodal, and AV nodal electrophysiology in standing horses: normal findings and electrophysiologic effects of quinidine and diltiazem. AB - BACKGROUND: Although atrial arrhythmias are clinically important in horses, atrial electrophysiology has been incompletely studied. HYPOTHESES: Standard electrophysiologic methods can be used to study drug effects in horses. Specifically, the effects of diltiazem on atrioventricular (AV) nodal conduction are rate-dependent and allow control of ventricular response rate during rapid atrial pacing in horses undergoing quinidine treatment. ANIMALS: Fourteen healthy horses. METHODS: Arterial blood pressure, surface electrocardiogram, and right atrial electrogram were recorded during sinus rhythm and during programmed electrical stimulation at baseline, after administration of quinidine gluconate (10 mg/kg IV over 30 minutes, n = 7; and 12 mg/kg IV over 5 minutes followed by 5 mg/kg/h constant rate infusion for the remaining duration of the study, n = 7), and after coadministration of diltiazem (0.125 mg/kg IV over 2 minutes repeated every 12 minutes to effect). RESULTS: Quinidine significantly prolonged the atrial effective refractory period, shortened the functional refractory period (FRP) of the AV node, and increased the ventricular response rate during atrial pacing. Diltiazem increased the FRP, controlled ventricular rate in a rate dependent manner, caused dose-dependent suppression of the sinoatrial node and produced a significant, but well tolerated decrease in blood pressure. Effective doses of diltiazem ranged from 0.125 to 1.125 mg/kg. CONCLUSIONS AND CLINICAL IMPORTANCE: Standard electrophysiologic techniques allow characterization of drug effects in standing horses. Diltiazem is effective for ventricular rate control in this pacing model of supraventricular tachycardia. The use of diltiazem for rate control in horses with atrial fibrillation merits further investigation. PMID- 17338166 TI - Estimation of acute fluid shifts using bioelectrical impedance analysis in horses. AB - BACKGROUND: Multi-frequency bioelectrical impedance analysis (MF-BIA) has been used to evaluate extracellular fluid volume (ECFV), but not fluid fluxes associated with fluid or furosemide administration in horses. If able to detect acute changes in ECFV, MF-BIA would be useful in monitoring fluid therapy in horses. HYPOTHESIS: The purpose of this study was to evaluate the ability of MF BIA to detect acute fluid compartment changes in horses. We hypothesized that MF BIA would detect clinically relevant (10-20%) changes in ECFV. ANIMALS: Six healthy mares were used in the study. METHODS: This is an original experimental study. Mares were studied in 3 experiments: (1) crystalloid expansion of normally hydrated subjects, (2) furosemide-induced dehydration followed by crystalloid administration, and (3) acute blood loss followed by readministration of lost blood. MF-BIA measurements were made before, during, and after each fluid shift and compared to known changes in volume calculated based on the intravenous fluids that were administered in addition to urinary fluid losses. Mean errors between MF-BIA estimated change and known volume change were compared using nonparametric analysis of variance. Estimated ECFV pre- and post-fluid administration similarly were compared. The level of statistical significance was set at P < .05. RESULTS: Results of the study revealed a statistically significant change in ECFV and total body water during crystalloid expansion and dehydration. Statistically significant changes were not observed during blood loss and administration. Mean errors between MF-BIA results and measured net changes were small. CONCLUSIONS AND CLINICAL IMPORTANCE: MF-BIA represents a practical and accurate means of assessing acute fluid changes during dehydration and expansion of ECFV using isotonic crystalloids with potential clinical applications in equine critical care. PMID- 17338167 TI - Plethysmographic comparison of breathing pattern in heaves (recurrent airway obstruction) versus experimental bronchoconstriction or hyperpnea in horses. AB - BACKGROUND: Horses with recurrent airway obstruction (heaves) are described as exhibiting "increased abdominal effort," but it is unknown whether this translates to an effective contribution to ventilation. HYPOTHESIS: We hypothesized that heaves is characterized by asynchrony between rib cage and abdominal motions, and that the abdominal component is the major contributor to ventilation. ANIMALS: The rib cage versus abdominal motion in naturally occurring heaves (n = 15) was compared to controls at rest (n = 7) and during hyperpnea because of lobeline treatment, and the effects of histamine-induced bronchoconstriction in controls (n = 10). METHODS: Flow patterns, phase angle (theta) between the rib and abdominal compartments, abdominal (Vabd) contribution to tidal volume (VT), and lung mechanics were measured. RESULTS: Findings unique to the heaves group included the loss of biphasic expiratory flow, severely increased theta with the abdomen consistently lagging behind the rib cage, and a reduced contribution of the abdomen to ventilation. A subgroup of heaves (n = 5) with abdominal paradox showed a significant (P < .05) reduction in tidal volume, and increased respiratory rate. Bronchodilation reduced theta in heaves (P = .06), but theta remained significantly higher after bronchodilation than found in controls. CONCLUSIONS AND CLINICAL IMPORTANCE: We conclude that breathing pattern in horses with heaves is characterized by severe rib cage/abdominal asynchrony, with the rib cage motion in synchrony with flow, therefore dominating ventilation. In a subset of heaves, the abdominal compartment (diaphragm, abdominal muscles) was completely out of synchrony with flow ("abdominal paradox") despite the clinical appearance of "increased abdominal effort." PMID- 17338168 TI - Paraneoplastic hypoglycemia due to an insulin-like growth factor type-II secreting hepatocellular carcinoma in a dog. PMID- 17338169 TI - A 10-base-pair deletion in the gene encoding platelet glycoprotein IIb associated with Glanzmann thrombasthenia in a horse. PMID- 17338171 TI - Regulation and function of the E2A proteins in B cell development. PMID- 17338170 TI - Inheritance, mode of inheritance, and candidate genes for primary hyperparathyroidism in Keeshonden. AB - BACKGROUND: Primary hyperparathyroidism (PHPT) is caused by inappropriate secretion of parathyroid hormone (PTH) by autonomously functioning neoplastic or hyperplastic parathyroid "chief" cells. Keeshonden are thought to be over represented in studies on canine PHPT, but no proof of heritability or mode of inheritance has been published. The canine disease clinically resembles human familial isolated hyperparathyroidism (FIHP). HYPOTHESIS: Primary hyperparathyroidism in Keeshonden is genetically transmitted and is caused by a mutation in 1 of 4 genes implicated in human FIHP: MEN1, CASR, HRPT2, or RET. ANIMALS: Pedigrees consisting of 1647 Keeshonden were created including 219 Keeshonden with known PHPT phenotypes (69 positive). DNA samples were obtained from 176 of the 219 Keeshonden (34 positive). METHODS: Heritability and mode of inheritance were determined by segregation analysis. Canine homologs to the human genes were identified. Exons and surrounding intron regions were sequenced and scanned for sense-altering polymorphisms or polymorphisms that segregated with the disease. Messenger RNA from a parathyroid tumor of an affected Keeshond was analyzed for polymorphisms and splice alterations. RESULTS: PHPT follows an autosomal dominant mode of inheritance in Keeshonden with possible age-dependent penetrance. No polymorphisms identified in the genes analyzed were associated with a change in predicted protein or in hypothesized splice sites. CONCLUSIONS AND CLINICAL IMPORTANCE: PHPT is an autosomal dominant, genetically transmitted disease in Keeshonden. Once the mutation locus is identified, genetic testing should quickly decrease the incidence of PHPT in this breed. It is unlikely that mutations in MEN1, CASR, HRPT2, or RET cause PHPT in Keeshonden. PMID- 17338172 TI - Multiple roles for Blimp-1 in B and T lymphocytes. PMID- 17338173 TI - Memory B cell evolution: B cell biology. PMID- 17338174 TI - BCR-linked factors in developmental fate decisions. PMID- 17338175 TI - Gene regulatory networks that orchestrate the development of B lymphocyte precursors. AB - The B cell developmental pathway represents a leading model within the hematopoietc system for the analysis of gene regulatory networks, which orchestrate cell fate specification and commitment. Considerable progress is being made in the characterization of regulatory components that comprise such networks and examining their connectivity. These components include the cytokine receptors Flk2 and IL-7R as well as the transcription factors PU.1, Ikaros, E2A, EBF and Pax-5. We review recent experimental evidence concerning the molecular functions of these regulatory components and attempt to connect them in sequentially acting and inter-dependent regulatory modules. PMID- 17338176 TI - Rules for the rearrangement events at the L chain gene loci of the mouse. PMID- 17338177 TI - Regulation of AID function in vivo. PMID- 17338178 TI - Targeting of AID to immunoglobulin genes. PMID- 17338179 TI - Targeting AID to the Ig genes. PMID- 17338181 TI - Regulation of activation induced deaminase via phosphorylation. AB - Immunoglobulin gene diversification by somatic hypermutation (SHM), class switch recombination (CSR), and gene conversion is dependent upon activation-induced cytidine deaminase (AID). AID is a single-stranded DNA specific cytidine deaminase that is expressed primarily in activated mature B lymphocytes. AID appears to catalyze DNA cytidine deamination of immunoglobulin heavy (IgH) and light chain (IgL) variable region (V) exons and IgH switch (S) region sequences to initiate, respectively, IgH and IgL somatic hypermutation (SHM) and IgH class switch recombination (CSR). Here, we will discuss the implications of recent studies that demonstrate the role of AID phosphorylation in augmenting AID activity with respect to these two processes. PMID- 17338182 TI - Modulation of MHC class II signal transduction by CD19. PMID- 17338180 TI - DNA replication to aid somatic hypermutation. PMID- 17338183 TI - Role of NFkappaB signaling in normal and malignant B cell development. PMID- 17338184 TI - Fc receptor-like proteins (FCRL): immunomodulators of B cell function. PMID- 17338185 TI - Tolerance mechanisms in the late phase of the antibody response. PMID- 17338186 TI - Role of RS/kappaDE in B cell receptor editing. PMID- 17338187 TI - The regulation of receptor editing. PMID- 17338188 TI - B cell hyporesponsiveness and autoimmunity: a new paradigm. PMID- 17338189 TI - [Age at the onset of intractable disease: based on a clinical database for patients receiving financial aid for treatment]. AB - OBJECTIVE: We examined a clinical database for patients receiving financial aid for treatment to elucidate age at onset of intractable disease. METHODS: Data were obtained from the clinical database of patients receiving financial aid for treatment in 2003. Age at onset of disease was calculated by subtracting the year of birth from the year of onset as registered in the database. Percentiles for age at onset and peak onset age were evaluated for each intractable disease. Peak onset ages for primary immune-deficiency syndrome, subacute sclerosing panencephalitis, lysosomal diseases, epidermolysis bullosa and neurofibromatosis I and II were under 20 years. RESULTS: Peak onset ages for aortitis syndrome, systemic lupus erythematosus, Behcet's disease, adrenoleukodystrophy, multiple sclerosis, ulcerative colitis and Crohn's disease were between 20 and 50. Distributions of age at onset for aplastic anemia, idiopathic thrombocytopenic purpura, myasthenia gravis, moyamoya disease and sarcoidosis were bimodal. Peak onset age for many other diseases were > or = 40 years. CONCLUSIONS: Using a clinical database for patients receiving financial aid for treatment, the distribution of ages at onset and peak onset ages could be systematically clarified for individual intractable diseases. Our study provides new information on the natural history of disease development. PMID- 17338190 TI - [A trial of community-based well-rounded training for women inhabitants aged 65 74]. AB - OBJECTIVE: Well-rounded training, composed of resistance training, aerobic training and flexibility exercise, has been shown to be beneficial for increasing the physical strength of the elderly. The purpose of this study was to investigate the effects of a trial of community-based well-rounded training on women inhabitants to strengthen leg muscles. METHODS: The subjects were the women aged 65 to 74 years living in E city, Gifu prefecture in Japan, who gave informed consent for participation in a community-based well-rounded training class in 2003 or 2004 (n = 24), while others taking part in a recreation class for the aged served as the controls (n = 15). The training class was performed once a week for 12 weeks, while the recreation class was conducted every two weeks for 12 weeks. Self-reported questionnaire surveys of health status and examinations of physical characteristics and physical fitness were conducted before the beginning of each class and after the end of the 12-week class. RESULTS: In the training class, the replies to the following items of questionnaires were significantly improved: "Are you confident in your present physical strength? (P < 0.01)", "How long can you walk at your ease? (P < 0.05)" and "How many times do you go out usually? (P<0.05)." On the other hand, there were no significant changes in the recreation class. Regarding physical fitness, both subjects and controls had significant improvements in a 10 meter-walking test, a body reaction time test and a 30-sec chair-stand test. In addition, training class attendees showed an increase in forward bending ability, an index of flexibility (P < 0.01), and the cross-sectional area of femoral region muscles measured by computer tomography (P < 0.05). CONCLUSION: The present trial in a community suggested that well-rounded training has some beneficial effects to increase or maintain the physical strength of the leg muscles and the flexibility of bending among inhabitants aged 65-74. Community-based well-rounded training programs for the aged will assume greater importance with the rapid increase in aging populations. PMID- 17338191 TI - [Healthy life expectancy and the standardized mortality ratio for the elderly in Japan's 47 Prefectures]. AB - OBJECTIVE: To derive values for life expectancy and healthy life expectancy (number of years people are expected to live without certification as being in need of long-term care) for Japanese at 65 years of age across 47 Prefectures in Japan, based on both national death statistics and long-term care insurance data, and to analyze their relationships with the standardized mortality ratio (SMR) for the elderly aged 65 years and more. METHOD: Life expectancy was calculated using Chiang's method and healthy life expectancy using Sullivan's method. The number of years of living with long-term care needed (duration of care need) was determined by subtracting the healthy life expectancy from life expectancy. The SMR was calculated in comparison with that for the nation set at 1. The relationships between the indices were analyzed based on the Spearman rank-order correlation coefficient. RESULTS: (1) Among the 47 prefectures, healthy life expectancy at 65 years of age in 2004 for males was the longest in Nagano Prefecture (16.72 years) and the shortest in Aomori Prefecture (14.32 years). For females, it was the longest in Yamanashi Prefecture (19.18 years) and the shortest in Osaka Prefecture (16.47 years). (2) Healthy life expectancy for males and females positively correlated with life expectancy, and negatively correlated with the duration of care need and SMR. Life expectancy negatively correlated with SMR for males and females, and, for females, it positively correlated with the duration of care need as well. CONCLUSION: (1) Among the 47 prefectures, healthy life expectancy at 65 years of age in 2004 was the longest in Nagano Prefecture and the shortest in Aomori Prefecture. For females, it was the longest in Yamanashi Prefecture and the shortest in Osaka Prefecture. (2) For males and females, lowering the mortality rate as well as the prevalence of ill health with long-term care need is important for extending healthy life expectancy. For females, long life expectancy is associated with a long duration of care needed. PMID- 17338192 TI - [Descriptive epidemiological study of intractable disease. Transition of sex and age characteristics among intractable disease patients receiving financial aid for treatment]. PMID- 17338193 TI - [Characteristics of urban community-dwelling elderly women with multiple symptoms of the geriatric syndrome and related factors]. AB - OBJECTIVE: The present study was performed to comprehensively investigate the prevalence of multiple symptoms of the geriatric syndrome, characteristics and related factors in urban community-dwelling elderly women. METHODS: Among 669 women aged 70 years and above living in 5 areas of Itabashi-ku, who attended the Otassha Kenshin (comprehensive health check for the elderly) in November 2004 and gave consent to participate in this study, 668 had no missing data and their interview and physical fitness data were analyzed. The criteria for the geriatric syndrome were: (1) functional decline: a score of 10 points or below for the 13 items of the Tokyo Metropolitan Institute of Gerontology (TMIG) index of competence; (2) falls: "have fallen" once or more in the last year; and (3) urinary incontinence: frequency of urine leakage of "1 to 3 times in a month" in daily life. The interview and physical fitness data were compared between healthy persons, persons with one symptom and persons with multiple symptoms. Multiple logistic regression models were used to analyse related factors. RESULTS: The prevalence of multiple geriatric syndromes was 15.3%; comprising 2.2% with "functional decline+falls", 6.0% with "functional decline+urinary incontinence", 5.1% with "falls+urinary incontinence", and 2.0% with "functional decline+falls+urinary incontinence". The group reporting multiple symptoms had poor self-rated health, had a high percentage currently taking three or more medications, had a fear of falling and had a significantly (P < 0.05) higher likelihood of a history of stroke and urinary disease. In addition, the group with multiple symptoms were older, and had significantly (P < 0.05) poorer results for grip strength, usual walking speed, maximum walking speed, functional reach, knee extension strength, and one leg standing time with eyes open. Within this group, the "functional decline+falls" subgroup had the lowest level of physical fitness. Analysis of factors related to the presence (1) or absence (0) of multiple symptoms identified fear of falling and usual walking speed as two significant variables. CONCLUSION: This study showed that: (1) physical fitness is significantly lower in the group with multiple symptoms of the geriatric syndrome compared with healthy persons, and was the lowest in the subgroup with "functional decline+falls"; and (2) fear of falling and usual walking speed were two factors related to multiple geriatric syndromes. These results suggest directions for future intervention strategies. PMID- 17338194 TI - Primary esophageal motility disorders (concise review for clinicians). AB - Primary esophageal motility disorders comprise various abnormal manometric patterns which usually present with dysphagia or chest pain. Some, such as achalasia, are diseases with a well defined pathology, characteristic manometric features, and good response to treatments directed towards the palliation of symptoms. Other disorders, such as diffuse esophageal spasm and nutcracker esophagus, have no well defined pathology and could represent a range of motility abnormalities associated with subtle neuropathic changes, gastresophageal reflux and anxiety states. On the other hand, hypocontracting esophagus is generally caused by weak musculature commonly associated with gastresophageal reflux disease. Although manometric patterns have been defined for these disorders, the relation with symptoms is poorly defined and in some cases the response to medical or surgical therapy unpredictable. The aim of this paper is to present a wide spectrum of the primary esophageal motility disorders, as well as to give a concise review for the clinicians encountering these specific diseases. PMID- 17338195 TI - Laparoscopic treatment for acute diverticular disease. AB - Diverticular disease of the sigmoid colon involves more than 50% of population over 60 years, and much more in people older than 80 years. Most patients remain asymptomatic, but, about 10-20% develop complications requiring surgery. Colonic diverticulitis represents an acute bowel inflammation, in many cases, confined only to the sigmoid and descending colon. Recurrent attacks and complications of diverticulitis require surgical procedure, although most cases can be managed medically. The cause of acute diverticulitis remains obscure. It has been speculated that obstruction at the mouth of the diverticulum results in diverticulitis, similar to appendicitis, but this is no longer the accepted theory, and some feel that chronic inflammation precedes clinical diverticulitis. PMID- 17338196 TI - [Surgery for patients with mechanical heart valves--adjustment and tailoring of anticoagulant therapy]. AB - Valvular surgery in patients (pts) with long history of cardiac valve disease is accomplishing improvement of symptoms, functional status and longevity. The numbers are very big also in our country. Our census numbers are not reliable, but estimation of above 15000 pts with prosthetic heart valve implants is close to correct. Since significant increase in survival and longevity of those pts, the possibility and necessity for non cardiac operative procedures are also increased. Because of specificity and complex constant regular anticoagulation therapy in order to prevent catastrophic prosthetic valve thrombosis and common thromboembolic complication good, but safe reduction of anticoagulation status to accomplish also safe haemostatic condition necessary for all surgical procedures. Individual adjustment and tailoring of anticoagulant and anti aggregation therapies according to accepted international protocols should be carefully done with necessery variation depending on the non cardiac organ and system involved: urgent either minor or major surgical interventions; bleeding peptic ulcer; elective surgery including ophtalmic and common dental procedures with risk of bleeding. PMID- 17338197 TI - Elevated serum uric acid reduce heart damage in patients undergoing opern-heart surgery. AB - OBJECTIVES: Peroxynitrite is species claimed to propagate ischemia/reperfusion damage. In this report levels of serum uric acid (UA), a peroxynitrite scavenger, are compared with creatine phosphokinase (CPK) in male patients before and after open-heart surgery in order to asses if increased levels of UA may protect heart from biochemical damage induced by peroxynitrite during the coronary by-pass grafting (CABG) intervention. METHODS: 45 male patients (16 carvedilol pretreated (6.25 mg/ daily, during 6 weeks before surgery, mean age 55.3+/-1.7 years, range 50-71) and 29 patients without carvedilol pretreatment (mean age 58.3+/-1.4 years, range 47-73) underwent elective CABG were examined. Study inclusion criteria were CABG performed on two and more coronary-vessels with aortic cross clamp during 30-40 minutes. For assessment of patients objective health status before operations EuroSCORE were used. Serum uric acid (UA) levels and creatine phosphokinase (CPK) were measured spectrophotometricaly by using a quantitative enzymatic assay. RESULTS: Carvedilol pretreated patients had higher amount of serum UA (p<0.05) comparing to non-treated patients. During the surgical procedure patients are subjected to temporary ischemia due to transfer from corporeal to extracorporeal circulation. In this period of time the amount of UA decreased in carvedilol pretreated group (406+/-46 (tl) vs. 300+/-22 mmol/L (t2)) to the level of non-treated patients (328+/-14 (t1) vs. 322+18 mmol/L. Carvedilol pretreated patients and non-treated patients had the same level of CPK at the beginning of the surgical procedure (tl) (78+/-6 vs. 83+13 U/L) but lower increase (p<0.05) in CPK activity in carvedilol pretreated patients in respect to non-treated patients (338+46 vs. 644+103 U/L) at the end of procedure (t2). Such results suggest that open heart surgery led to elevated CPK levels, but this effect was less pronounced in patients with higher level of UA. CONCLUSIONS: Our results suggest possible role of UA in the protection from reperfusion injury. Increase of UA before surgery may be beneficial factor during CABG procedure in patients treated with carvedilol by decreasing level of peroxynitrite as one of molecular causes of reperfusion injury. Our results showed influence of UA on CPK levels at the end of surgical procedure, indicating that increased levels of UA may protect heart from biochemical damage induced by peroxynitrite during the CABG intervention. PMID- 17338198 TI - [Preoperative procedures in diagnosis of central and peripheral lung cancer]. AB - BACKGROUND: Actual problem in diagnostics and therapy of lung cancer is early diagnostic and choice of diagnostic procedure. The AIM of this work was to assess the sensitivity of various histocytologic methods in diagnosis of central and peripheral lung cancer lesions. MATERIAL AND METHODS: During 2003-2004, 348 patients with lung infiltrates suspect for malignancy were treated in University of Kragujevac Clinical Center. For the preoperative diagnostics, their sputum, bronchoaspirate, aspirate obtained by fine needle percutaneous biopsy and specimens obtained by forceps biopsy during fiber-bronchoscopy were analyzed using standard cytohistology methods. RESULTS: Lung cancer was diagnozed in 155 out of 348 patients. The malignant lesions were centrally located in 123 patients (79,4%), while peripheral localization was found in 32 patients (20,6%). In the former patients, forceps biopsy was positive in 89,4%, and when combined with bronchoaspirate analysis, positive results were obtained in 91,9% of patients. In patients with peripherally located lesions, fine needly biopsy was positive in 68,8%, while citological analysis of sputum and bronchoalveolar aspirate were positive in only three (9,4%) patients. When all three methods were combined, positive results were found in 25 (78,1%) patients. CONCLUSION: The central localization of tumors was four times greater than the peripheral one. In the patients with central tumour site, the best results were obtained when forceps biopsy specimens and sputum were analysed cytologically. The combination of transcutaneous fine-needle biopsy, bronchoscopy and sputum gave the best results in the group of patients whose lesions were located peripherally. PMID- 17338199 TI - [The influence of Helicobacter pylori eradication on appearance of gastro oesophageal reflux disease]. AB - Gastro-oesophageal reflux disease (GERD) includes wide spectrum of symptoms caused by gastric acid regurgitation through the incompetent lower oesophageal sphincter in oesophagus. Etiopathogenesis of GERD is multifactorial. AIM OF THIS STUDY: to establish the relationship between Helicobacter pylori eradication and appearance or aggravating of present GERD. If this relationship exist, the aim is to estimate its level and clinical consequences. MATERIAL AND METHODS: 50 Helicobacter pylori positive patients with different endoscopic findings (ulcer disease, gastritis and non-ulcer dyspepsia) to whom eradication of Helicobacter pylori was done, were following next 6 months. Questionnaire, uppear GI endoscopy with verification changes of oesophagus in accordance to LA classification, histopathological examination of gastric and oesophageal mucosal biopsy specimens, and oesophageal manometry have been done to all patients. These examinations have been done before Helicobacter pylori eradication and one, three. six and none months after that. RESULTS: non statistical significant difference was found among the appearance or aggravating of present GERD in all patients during the following period (Cochran Q test; p=0,408). Non statistical significant difference was found among the endoscopic types of oesophagitis (LA classification) in all patients during the following 6 months (Friedman test; p=0,058). Non statistical significant difference was found among the changes of histopathological findings on distal oesophagus, too (Friedman test; p=0,217). CONCLUSION: Eradication od Helicobacter pylori infection does not cause the appearance or aggravating of present GERD. The presence of mildly form of GERD, or aggravating of present GERD is transitory, and haven't the statistical signification. PMID- 17338200 TI - [Importance of the length of excised optic nerve in enucleations for uveal melanoma]. AB - The importance of a length of excised optic nerve in eyes enucleated for uveal melanoma isnt finaly discussed. We analyzed 473 eyes enucleated for uveal melanoma between 1995. and 2004. at Institute of opthanlmology in Belgrade, 16 (3,7%) of which extended into the optic nerve or its meningeal sheaths. Peripapillary melanomas and large melanomas in eyes with increased intraocular pressure and poor vision were associated with optic nerve invasion. This tumors, as a rule, require an enucleation as a treatment of choice. Autors suggest that a long piece of optic nerve should be excised when eyes with uveal melanomas are enucleated. PMID- 17338201 TI - [The excision width in surgical treatment of basal cell carcinoma]. AB - Basal cell carcinoma originates from pluripotent cells of basal layer of epiderm, external covering of hair follicles, sebaceous glands or other skin adnexa. It is characterized by local infiltrating and sometimes destructive growth. There are several types of basal cell carcinomas that may be manifested in over 12 clinical forms. Surgical treatment depends to a large extent on the histological type, localization and its clinical manifestation. The analysis included 250 patients of both gender and different age, operated for basal cell carcinoma. Clinical characteristics of basal cell carcinoma and the width of the excision were described. It was concluded that the width of the excision of basal cell cancer was in relation to histological type. PMID- 17338202 TI - [Palliative operations for lung cancer]. AB - The goal of the palliative resection can be threefold: relief of symptoms without expected survival benefit, obviation of an urgent situation and maintenance or restoration of a good quality survival. Clear distinction should be made between this type of operation and incomplete resection: in spite of a curative intent, the latter type of operation is characterized either by residual disease or positive most distal lymph node station. Classification of palliative operations for lung cancer based on the underlying pathology seems to be most suitable for clinical use: 1) tumours without extrapulmonary extension; 2) tumours with direct involvement of adjacent organs; 3) metastatic involvement of intrathoracic or distant organs; 4) lung tumours associated with nonmalignant pathology (lung suppuration, pleural empyema). Although palliative operations for lung cancer can be considered in carefully selected patients, they should always be avoided if other, less aggressive non-surgical procedures offer the same quality of palliation. PMID- 17338203 TI - Diagnosis and surgical therapy of uterine sarcoma. AB - INTRODUCTION: Uterine sarcomas are rare gynaecological neoplasms and their classification is complicated. Uterine sarcoma is usually diagnosed in postmenopausal women and the diagnosis is often accidental and postoperative. Aim of this study was to present clinical and pathological characteristics of uterine sarcomas, diagnostic procedures, treatment and two-, three- and five-years cumulative survival rates. MATERIALS AND METHODS: The retrospective study of 61 cases of uterine sarcomas was conducted. Cases were distributed into groups based on definitive diagnosis of uterine sarcoma: group of leiomyosarcomas (LMS), carcinosarcoma (CS), endometrial stromal sarcomas (ESS), adenosarcomas (AS) and other rare uterine sarcomas. We investigated patients with clinical and pathological characteristics of uterine sarcomas, diagnostic procedures and treatment. Survival rate was calculated by Kaplan-Meier method. RESULTS: From 61 patients 43 patients (70.49%) were postmenopausal. Mean period from menopause until appearance of symptoms was 14,63 years. One or more risk factors were present in 46 (75.4%) patients. Diagnosis of uterine sarcoma were established averagely 7.38 months after appearance of symptoms. 50 patients (82.0%) underwent one or more diagnostic procedures. Preoperative diagnosis of uterine sarcoma was established in 42.5% of patients. 53 (86.9%) of patients were treated operatively. The most used operative procedure (60,7%) was total hysterectomy with bilateral salpingooophorectomy. Postoperative pathohistologic analysis showed that low grade (LG) leiomyosarcoma were present in 19 (35.9%) cases, high grade (HG) leiomyosarcoma in 1 (1.9%) case, carcinosarcoma in 14 (26.4%) cases, low grade (LG) endometrial stromal sarcoma in 5 (9.4%) cases, high grade (HG) endometrial stromal sarcoma in 9 (17.0%) cases, adenosarcoma in 2 (3.8%) cases, and 2 cases of rare uterine sarcomas: 1 (1.9%) MALT HG lymphoma and 1(1.9%) malignant hemangiopericytoma. In one case of ESS (1.9%) only adenomyosis was found postoperatively suggesting that the whole tumour was removed during diagnostic procedure. Eight patients were not treated operatively. Two-years cumulative survival rate was 74.3%, three-years cumulative survival rate was 71.1%, and five years survival rate was 64.3%. DISCUSSION: Average age, percent of postmenopausal patients and the mean age at the time of menopause in our studied correlate with current data. Clinical presentation of uterine sarcoma is associated with obesity and hypertension in more than 30% of cases, which is approved in our study. For early diagnostics it is important to notice that risk factors are similar to those connected with far more frequent endometrial carcinoma. Postmenopausal abnormal bleeding was the main reason for medical examination, explaining relatively short period for establishing the diagnosis in this group of patients. The variety of clinical findings in our studied group showed that the diagnosis must be based on preoperative pathohistology. CONCLUSION: Adequate diagnosis and treatment of uterine sarcoma is possible with regular yearly or more frequent follow-up, especially in postmenopausal women with known risk factors present. We need special attention for unclear symptoms and postmenopausal bleeding and we need to use all diagnostic procedures soon as possible including preoperative histology because early metastases are characteristic for uterine sarcomas. Factor of the most important predictive value is histologic grade. PMID- 17338204 TI - [The influence of duration of Kleinert immobilization on the functional recovery of primarly reconstructed flexor tendons in children and adult patients]. AB - Flexor tendon repair in the hand is very often complicated by the formation of peritendinous adhesions that result in loss of normal tendon gliding, digital stiffnes and functional disability. While stability is critical for a successful tendon repair, mobility is also important, as motion of the repaired tendon decreases the formation of postoperative adhesions and increases the strength of the repair. Immobilization and its duration, can ensure the integrity of the repair but can also lead to scaring, stiffness, and joint contractures. This study included 20 children and 39 adult patients, in the period from January 2000 to April 2003., with flexor tendon ruptures of the hand. Tendons were primary repaired using direct tennoraphy, and postoperately patients were treated with Kleinert dynamic imobilization. The aim of this study was to investigate the influence of the duration of the dynamic immobilization on successful postoperative functional recovery, separately in children and adult patients. Research in this area has been directed at achieving the optimal balance between stability and mobility, without compromising one for the other. PMID- 17338205 TI - Visceral metastases of melanoma-single institution experience an analysis of 15 cases. AB - Authors analysed 15 cases with visceral metastasis of melanoma. In eight cases the primary was unknown but in seven cases the data about primary was known. From 15 patients 10 were male and 5 female. All metastases were in abdominal cavity (liver-3, abdominal lymph nodes-4. stomach-2, bowel-4, omentum-1, spleen-1, oesophagus-1, adrenal-2 cases. In one case metastatic deposit was in brain and in one case i the vertebral body. In 6 cases visceral metastases were in more than one location. PMID- 17338206 TI - [Anal canal melanoma-- case report]. AB - Anal canal melanoma is a rare disease comprising 1% of all colorectal ie. anal malignant tumours with very poor long term prognosis. Its significant biologic aggressivity is the consequence of the tendency towards lymphatic, local and hematogenous spread. At the moment of diagnosis even 30% of the patients have distant metastases. Surgical intervention represents the only possibility for cure. Modern approach to the anal canal melanoma treatment implies two types of intervention: wide local excision preserving the sphincter mechanism and abdominoperineal resection of the rectum. There are numerous dillemas about the choice of surgery in particular disease stages. The authors report on a 61 years old women in which anal canal melanoma with left inguinal lymphatic metastases was detected during the inspection of "haemorrhoids". After the diagnosis was established, abdominoperineal resection of the rectum was performed with dissection of both inguinal regions. PMID- 17338207 TI - [Risk factors in chronic ischemic pancolitis]. AB - Ischaemia of the colon wall leads to lesions that are gathered under entity of ischaemic colitis. Acute or chronic tissue hypoxia is caused by various vascular disorders which could be divided into two large groups: occlusive or non occlusive. Chronic ischaemic colitis is manifested with necrosis of colon wall, with consequent stenosis of the affected area. Clinically, it is manifested with increased number of bloody stools and abdominal pain. Treatment of choice is surgery, and resection of the affected segment is often life saving. We present a case of a patient with chronic ischaemic pancolitis, due to atheromathosis of upper and lower mesenterial arthery branches, corelated with age, cardiovascular diseases, chronic opstipation and drug-intake. PMID- 17338208 TI - [Surgical treatment of a 5 month pregnancy in the rudimentary uterine cornu]. AB - Cornual ectopic pregnacy is rare clinical entity with high maternal mortality. In all cases surgical treatment is indicated, and taking care of most important complication--haemorrhagic shock. Therapeutic approach is individual and depending of simptomatplogy, gestational age of pregnancy and condition of the patient in time of diagnosis. Authors are presenting the case of cornual ectopic pregnancy of five months. PMID- 17338209 TI - [Fournier's gangrene and reconstruction of its defects]. AB - Fournier's gangrene is remarkebly rare but severe, life threatening condition. Thanks to better earlz recongnition of disease in past few years, the percentage of patients which survive this condition is considerable, but consequence of this fact is large number of patients with defects of cutis and subcutis in perineal and scrotal reigions. Reconstruction of this defects is cimplicate and require helathy, well vascularised tissue from another anatomical region which is not involved in gangreneous process. Authors present two cases of reconstruciton of defects in perineal and scrotal regions. First case is large defect which is covered by transposition of musculus gracilis musculo-cutaneous flap. Second case is lesser defect which is enclosed by mobilisation of local skin flaps. PMID- 17338210 TI - [90th Anniversary of the "Morphology" ("Archive of Anatomy, Histology and Embryology") journal]. PMID- 17338212 TI - [Electron microscopic characteristics of the neuroendocrine neurons of the amygdaloid body of the brain in male and female rats at different stages of estrous cycle]. AB - Ultrastructural characteristics of neuroendocrine neurons were studied in amygdala dorsomedial nucleus (DMN), which is one of main zones of sexual dimorphism, in 12 Wistar rats with the body mass of 250-300 g, 3 males and 9 females at different stages of the estrous cycle. In each animal, an average of 50 DMN neurons were examined and their functional state was analyzed on the basis of their ultrastructural characteristics. Morpho-functional classification is proposed, that reflects hormone-dependent variations in neuronal activity. It was established that DMN neurons could be found in different structural and functional states, that may be classified as the state of rest, moderate activity, increased activity, stress (peak activity), decrease in activity (two types), return to an initial state and apoptosis. At the stage of estrus, the neurons in the state of increased activity (40% of the total population) and peak activity (26%) were found to prevail. In metestrus, most of the neurons were in the state of type I decrease in activity (with an increase in nuclear heterochromatin content--30% of the cells); peak activity and increased activity were found in 25% and 20% of neurons, respectively. In diestrus, the neurons in the state of rest, moderate and increased activity, peak activity and type I decrease in activity were represented in approximately equal proportions (18%, 21%, 18%, 20% and 16%, respectively). In males, 35% and 22% of neurons, respectively, were found in the state of increased activity and peak activity. Neuronal death was detected only in males. PMID- 17338211 TI - [Defense mechanisms of the surface epithelium of the human esophageal mucosa]. AB - This review, which is based on the literature data and the results of personal research, contains an analysis of the current concepts on the tissue, cellular and molecular mechanisms, protecting human esophageal epithelium (EE) from gastric juice, bile, hot and rough food, microorganisms, alcohol, carcinogens, drugs and oxidizing agents. The response of EE to concrete environmental factors includes both specific and non-specific components, which depend on the nature of injurious agent. EE is damaged structurally and functionally only when it is exposed to the injurious factors of high intensity and/or long duration, which result in the exhaustion of resources of defense mechanisms. The insufficiency of EE defense mechanisms may be based on various genetic defects. PMID- 17338213 TI - [Striopallidum projections to the pedunculopontine tegmental nucleus in the dog mesencephalon]. AB - Using the method based on the retrograde axonal transport of the horseradish peroxidase, striopallidal afferent projections to the pedunculopontine tegmental nucleus (PPN) of the dog brain were studied. It was shown that the main source of these projections was pallidum, since the projections were directed both to the compact and diffuse parts of this nucleus from all its structures: nucleus entopeduncularis, globus pallidus and ventral pallidum. In the striatal complex, namely in the nucleus accumbens, only single labeled neurons projecting exceptionally to the compact part of the PPN, were detected Since in the distribution of the projection fibers, originating from the functionally various territorries of the striopallidum and directed to the individual substructures of the PPN, no topical elements were detected, the separation of the functionally specific (motor and limbic) regions in the PPN, on the basis of findings obtained, appears impossible. PMID- 17338214 TI - [Changes in expression of apoptosis-associated molecules in hypothalamic neurosecretory cells of mice during aging]. AB - The aim of work was to study the peculiarities of apoptosis regulation in neurosecretory centers of old (aged 18 months) mice treated with immunomodulator interferon alpha (IFN-alpha) as compared to young (aged 2 months) mice. It was shown that age-related apoptosis activation in supraoptic (SON) and paraventricular (PVN) nuclei was mediated by different molecular mechanisms and could result from the alterations of the balance of apoptosis-associated proteins, including the synthesis of proapoptotic (Bax) and antiapoptotic (Mcl-1, Bcl-2) molecules. Besides, the apoptosis signal cascade in young mice treated with IFN-alpha was identical in both nuclei, whereas in old mice there were some differences between SON and PVN. PMID- 17338215 TI - [Changes in the focus of experimental ischemic stroke under the influence of neuroprotective drugs]. AB - The purpose of this study was to compare the morphological changes in the focus of ischemic stroke under the influence of the drugs of neurotrophic group (alpha GPC, cerebrolysin), drugs possessing the nootropic properties (piracetam) and those with combined effect (vinpocetin). The experiments were performed in 18 rats. Temporary disturbance of cerebral circulation (acute ischemia) in right cerebral hemisphere was induced by clipping the trunk of innominate artery for 40 minutes. Areas of cerebral cortex, brainstem and cerebellar cortex were studied using light and electron microscopy. Treatment with alpha-GPC or cerebrolysin resulted in an increased tolerance of neurons to ischemic damage and in delayed realization of the program of cell death. Some intracellular changes were detected that could be regarded as the signs of adaptation and repair (indentation of nuclear envelope, increased number of ribosomes, hypertrophy of endoplasmic reticulum and Golgi complex). These drugs preserved the structure of the membranes in the nucleus and major organelles. In animals treated with piracetam and vinpocetin, all morphological signs were indicative of insufficient supply of energy-consuming processes of repair in the acute phase of ischemic stroke. This was accompanied by morphological features of functional stress of the neurons of the cerebral cortex, different stages of gliocyte apoptosis, phenomenon of incomplete separation of gliocytes during their proliferation, myelin and unmyelinated nerve fiber pathology, as well as by changes in synapse structure. PMID- 17338216 TI - [Structural organization of neurons of spinal ganglia innervating the colon]. AB - The localization and morphological features of viscerosensory neurons of sacral spinal ganglia (SSG), innervating the colon, were investigated. In urethane anaesthetized cats, the solution of horseradish peroxidase was injected under the serosa of ascending and descending parts of the colon as well as of the rectum. After 48 hours animals were repeatedly anesthetized and transcardially perfused. Sections of SSG were stained according to Mezulam protocol (1978). All the regions of the colon studied were shown to receive afferent innervation from neurons of SSG SI, SII and SIII. Maximum number of the labeled cells was detected in SSG SII. The intensity of afferent innervation of the colon by the neurons of SSG was found to increase along its length in cranio-caudal direction. PMID- 17338217 TI - [Changes of the liver blood vessels in the pulmonary trunk stenosis at compensation and decompensation]. AB - Changes of liver blood vessel structure were studied in 23 pups with the model of compensated pulmonary trunk stenosis and in 8 animals with decompensated stenosis during 6-24 months after the establishment of stenosis. The liver of 10 age matched dogs was used as a control. Material was studied using histological, morphometric and stereometric methods. It was found that after the establishment of pulmonary trunk stenosis and compromise to venous blood outflow from the liver, the tone of the arteries increased as well as the resistance to the blood flow. Besides the venous-arterial reaction, the bundles of oblique-longitudinal smooth muscle cells and musculo-elastic sphincters were shown to be formed in the intima of the afferent vessels, while in the efferent vessels the hypertrophy of the muscular folds took place. In decompensated stenosis, the hypoxia was combined with the relaxation of the walls of both afferent and efferent vessels, the number of arteries with the adaptational structures was decreased, while the muscular folds of hepatic veins underwent atrophy. The failure of adaptation mechanisms resulted in the development of chronic liver venous congestion. PMID- 17338218 TI - [Accidental thymic involution in the growing body under the effect of different types of stressors]. AB - Using the quantitative immunohistochemistry, the immunomodulatory effect of different types of stressors (physical and psychoemotional) on the thymus of growing experimental animals was assessed. Sprague-Dawley rats aged 21 day were exposed either to physical (water immersion) or emotional "expectation" stress for 5 hours daily during 7 consecutive days. After the final exposure to stress, animals were sacrificed, thymus was obtained for weighting and was processed for routine histology and immunohistochemistry (CD3, CD8, ED1, PCNA) with subsequent automatic image analysis. The finding obtained have demonstrated severe accidental thymic involution in both groups of experimental animals, which was more prominent under the effect of the physical stressor as compared to "purely" psychoemotional stressor. The major factors of poststress thymic hypoplasia were the increased apoptosis of the cortical thymocytes and inhibition of their proliferation, but not their increased transport to peripheral immune organs. PMID- 17338219 TI - [Morphological and functional changes in the esophageal epithelium after treatment with a cytostatic agent]. AB - Using histological, morphometric, histochemical and immunocytochemical methods, the effect of cytotoxic treatment on structural and functional characteristics of the epithelium of esophageal mucosa was studied in mice together with the reversibility of the changes induced by cytotoxic drug. Fourfold intraperitoneal injection of cyclophosphamide (400 mg/kg of body mass) resulted in such morpho functional changes, as thickening of epithelial layer, increase in proportion of its stratum corneum and its loosening, disturbances in cornification process, hyperkeratosis, vacuolization of cell cytoplasm in stratum basale and stratum spinosum, interstitial edema, nuclear hypertrophy and parakeratosis. Mitotic activity and the activity of NADH-diaphorase were significantly reduced, while the number of PCNA' cells was increased. Cyclophosphamide had no significant affect on the concentration of total proteins. 15 days after the discontinuation of cytostatic treatment, most of the indexes did not return to normal values, indicating profound disturbances in the esophageal epithelium. PMID- 17338220 TI - [Ultrastructure of endocrine cells in the dog pancreas]. AB - Electron microscopy was used to study the cellular composition of dog pancreatic islets. Four types of endocrine cells were detected: A, B, D and PP. B cells were the predominant population within the islets. Differences in cellular organization of A and B cells were shown to be caused by the phases of the process of hormone synthesis. Insulin-containing secretory granules in B cells had a crystalloid structure, similar to that in B granules of insulin-containing cells in human pancreatic islets. In the exocrine portion of the pancreas, acino insular cells were detected that simultaneously contained B granules and zymogen granules in their cytoplasm. It is suggested, that their presence is indicative of one of possible directions of pancreatic islet regeneration. PMID- 17338221 TI - [Histochemical analysis of glycoproteins in human bulbourethral glands]. AB - Neutral and acid glycoproteins were detected histochemically in the acinar and ductal cells of the bulbourethral glands. Most of acid glycoproteins in all the glandular cells could be identified as sialomucins. Small amounts of sulfomucins were demonstrated in some secretory acini. Glycogen was not detected in the glands. PMID- 17338222 TI - [Optimization of the immunocytochemical detection of nestin in paraffin sections of the rat brain]. AB - The aim of this study was to develop an optimal and easy protocol for immunocytochemical demonstration of nestin (an intermediate filament protein which is believed to be a neuronal stem cell marker) in paraffin sections of rat brain with target retrieval procedure being omitted for better preservation of the neural tissue structure. The influence of fixation, character of blocking of nonspecific antibody binding, temperature and time of incubation on the results of immunocytochemical reaction was studied. On the basis of the results obtained, we propose a processing protocol allowing distinct demonstration of nestin in rat brain cells together with the optimal preservation of the nervous tissue structure. PMID- 17338223 TI - [Isolation of cells for cytological and cytogenetic studies of the thyroid epithelium]. AB - This paper presents a detailed description of the method for obtaining of high quality smears of thyrocytes from the fragments of rat (30 animals) and human (20 cases) thyroid gland using the method of enzymatic dissociation in 0.25% aqueous solution of collagenase (collagenase for pancreatic islet isolation type XI, collagen digestive activity 1205 units/mg, Sigma, USA) at 37 degrees C during 1; 1.5; 2; 2.5 and 3 hours. Optimal time for dissociation in each individual case should be determined using control smears. This approach permitted to successively perform morphological, morphometric and cytophotometric analysis of the glandular cells, to evaluate the relative proportions of different cell types (mitotically dividing cells, binucleate cells, aberrant forms with the micronuclei) in animal experiments as well as in the various types of human thyroid pathology. PMID- 17338224 TI - [Stem cells and reparative regeneration in mammalian postnatal ontogenesis]. AB - This paper presents the critical analysis of the data published in recent literature, which concern the role and significance of stem cells (embryonic stem cells and progenitor cells) in the processes of reparative morpho- and histogenesis in the different animal and human organs. Possible negative effects of the application of stem cells for the stimulation of reparative histo- and organogenesis are discussed. Special attention is drawn to the necessity of more cautious and balanced approach to the use of stem cells for stimulation of repair processes in the organism. PMID- 17338225 TI - [Test control of knowledge during the study of anatomy at a physical culture institute]. PMID- 17338226 TI - [Contribution of V. G. Eliseev into national histology (to 40th anniversary of his death)]. PMID- 17338227 TI - [Vaccines and chemicals for the prevention of influenza]. AB - The review gives data on the reactogenicity, immunogenicity, and protective efficacy of the existing influenza vaccines, such as inactivated (conjugate, subunit, virosomal, cultural vaccines with adjuvants) and live vaccines, as well as on the new directions in the design of influenza vaccines. It also provides data on specific medications against influenza and discusses the problem associated with the occurrence of influenza viruses resistantto these drugs. The economic efficiency of the prevention of influenza with vaccines and drugs is under debate. PMID- 17338228 TI - [Molecular mechanisms of Ebola virus reproduction]. AB - The review presents recent data on the molecular mechanisms of the stages of an Ebola virus replication cycle, on the interaction of viral and cellular components at each stage, as well as on the mechanisms responsible for he realization of viral genetic information in the infected cell. PMID- 17338229 TI - [Genetic characteristics of HIV-1 subtype G reverse transcriptase gene]. AB - The paper presents data of a study of the structure of reverse transcriptase gene in the population infected with HIV subtype G formed during the 1989 HIV infection outbreak in the North-Caucasian region. The authors analyzed 3 samples obtained in 1993-1994 and 17 samples taken in 2000-2001. The phylogenetic analysis indicated that polymerase of the test virus variants belonged to HIV-1 subtype G. The mutations occurring with azidothymidine therapy did not differ from those in subtype B. Analysis of the mutations of resistance to other nucleoside and non-nucleoside reverse transcriptase inhibitors did not show great differences from subtype B either. PMID- 17338231 TI - [Regulation of human fibrolastic 2',5'-oligoadenylate synthetase gene activity in cytomegalovirus infected fibroblast cells]. AB - Great differences were found in the level of 2',5'-oligoadenylate synthetase 40 46 kDa (OAS1) mRNA in relation to the proliferative state of human diploid fibroblasts at the moment of cytomegalovirus (CMV) (the strain AD169) infection. In the phase of synthesis of cellular cycle DNA (S), CMV induced OAS1 mRNA transcription by 10-100 times stronger than then in phase Go infection. The level of viral induction OAS1 mRNA peaked by hour 12 postinfection. The high gene activity correlated with suppressed DNA synthesis, a slowing-down mitotic cycle, markedly inhibited CMV replication, and delayed cell death. When the cells were infected in phase Go, the stimulation of OAS1 gene activity was less and it was attended by intensive viral replication and rapid cell death. There was a direct relationship between the resistance of cells and the constitutive level of OAS1 gene expression: in the low CMV-sensitive cells, the activity of OAS1 gene was more than 10 times greater than that in the highly sensitive cells. The inhibitors of the enzymatic OAS activity induced by IFN and dsRNA were found in the cytoplasm of the CMV-infected cells. PMID- 17338230 TI - [Reassortment and gene interactions in the crossing of low-pathogenic avian influenza H5 virus with human influenza virus]. AB - The reassortants obtained via the crossing of highly productive influenza virus A/Puerto Rico/8/34 (H1N1) strain and the low pathogenic avian influenza virus A/Duck/Primorie/2621/2001 (H5N2) strain were genotyped and characterized. The H5N2 reassortant having 6 genes from A/Puerto Rico/8/34 virus has the high level of reproduction in chick embryos, while slightly more moderate than in the parent A/Puerto Rico/8/34 strain. The reproduction of the H5N1 reassortant that had 7 genes from A/Puerto Rico/8134 virus was very low. The serial passage selection allowed the investigators to obtain the H5N1 strain that was reproductively close to the H5N2 reassortant. This variant had one amino acid substitution in hemagglutinin (N244D, H3 numbering) and a lower affinity for fetuin. By the level of virulence to mice, the H5N1 and H5N2 reassortants were close to A/Puerto Rico/8/34 virus and greatly differed in this respect from low virulent A/Duck/Primorie/2621/2001 (H5N2). The results are discussed in connection with the problem of vaccination when there is a threat for H5N1 virus subtype-caused pandemic. PMID- 17338232 TI - [Hepatitis E virus antibodies in the macaques and in the personnel serving the macaques of the Adler apery]. AB - There is evidence for the rather high detection rate of antibodies against hepatic E virus (HEV) was rather high in the macaques from the Adler apery in 1999-2005. Anti-HEV was detected in 232 (57.3%) out of 405 examined rhesus macaques (Macaca mulata) and in 16 (16%) out of 100 Java ones (M. fascicularis). The detection rate of anti-HEV ranged from 12.5 to 89.5%% among the rhesus macaques and from 5.9 to 37.5% among the Java ones. Class M anti-HEV was found only in 3 (4.3%) out of 69 Java macaques and in none of the rhesus ones. Of importance are the data of detection of anti-HEV in 3 (7.5%) out of 40 examined employees of the Research Institute of Medical Primatology, all 3 (18.8%) out of 10 employees looking after the monkeys that belonged to the highest-risk group. The epidemiological and epizootological aspects of this infection require further studies. PMID- 17338233 TI - [Humoral immune response of BALB/c mice immunized with chimer HBcAg proteins carrying the epitopes of surface hepatic B virus protein]. AB - Chimeric HBcAg proteins carrying epitopes from surface hepatitis B virus (HBV) protein (regions 137-147 a.o. HBsAg, 27-37 a.a. region preS1 and 131-145 a.a. region preS2) have been early constructed. This paper presents the data of an investigation of a humoral immune response in mice immunized with obtained by chimeric HBcAg proteins. The findings suggest that the chimeric HBcAg proteins carrying the epitopes of surface HBV protein are able to induce an immune response to both inserted epitopes and carrying protein (HBcAg). Immunization with a mixture of chimeric proteins taken in equivalent quantities induces the synthesis of antibodies to hybrid proteins. The use of aluminum hydroxide considerably enhances a humoral immune response during immunization with chimeric bovine proteins. PMID- 17338234 TI - [The spectrum of vetebrates' cell lines sensitive to highly pathogenic influenza A/tern/SA/61 (H5N3) and A/duck/Novosibirsk/56/05 (H5N1) viruses]. AB - The reproduction of highly pathogenic avian influenza (HPAI) A/tern/SA/61 H5N3 and A/ducklNovosibirsk/56/05 H5NI viruses was comparatively studied in 16 human and animal cell lines. The strain A/duck/Novosibirsk/56/05 was shown to have a wider range of hosts. The most sensitive transplanted cell lines were found to be feline fibroblasts (CC-81), primarily trypsin-treated cells of chick embryonic fibroblasts (CEF), the kidney of dogs (MDCK), pigs (SPEV), monkeys (Vero), the human conjunctiva (1-5C-4), and, to a lesser extent, the feline kidney (CRFK). Unlike the strain A/tern/South Africa/61, that A/duck/Novosibirsk/56105 replicated in the polecat brain cells (Mpf). PMID- 17338235 TI - [Role of glycolysis in initiation of immortality and apoptosis]. PMID- 17338236 TI - [Specifics of surgical treatment of non-small-cell lung cancer associated with tuberculosis]. AB - Small cell lung cancer incidence associated with tuberculosis is 4.5-7 times that in a relevant population of tumor patients. Tuberculosis which masks tumor and metastatic spread to the mediastinal lymph nodes taxes the patient's potential. Treatment of such pathology involves increased rates of intraoperative complications, pulmonectomies, suture failure risk in primary bronchus stump and postoperative mortality. PMID- 17338237 TI - [Tentative results of using 99mTC-methoxyisobutyl isonitrile in predicting the effect of preoperative chemotherapy for locally advanced breast cancer]. AB - The investigation was concerned with use of 99mTc-methoxyisobutyl isonitrile (99m Tc-MIBI)-assisted prognosis for chemotherapy of locally-advanced breast cancer based on the assessment of 99m Tc retrieval from primary tumor in 26 patients. 99mTc was administered in the course of two-phase scintigraphy of the breast prior to chemotherapy. The dynamics of accumulation and withdrawal from tumor was identified. In view of the absence of any correlation between accumulation and chemotherapy efficacy, one was established between high rates of label withdrawal, on the one hand, and lack of pathomorphosis, on the other, while medium and low rates were associated with marked pathomorphosis in 44 and 50%, respectively (p < 0.05). PMID- 17338238 TI - [Solitary fibrous tumor: a clinico-morphological and immunohistochemical study]. AB - Solitary fibrous tumor is a rare neoplasm which may occur at any site although it is more frequent in the pleura, mediastinum and lung. The study used 4 cases of tumor localization in the pleura and orbit. Three cases presented as a "hemangiopericytic" variety of spindle cells; there were numerous giant cells in orbit tumor. Solitary fibrous tumor revealed enhanced expression of vimentin, CD34, bel-2 and CD99. Expression of S-100, desmine and non-striated muscle actin was found in few cells in some cases. Such features as large size (over 10 cm), necrosis, high cellularity, nuclear polymorphism and high mitotic index (more than 4 mitoses within 4 visual fields, at high magnification) were used as malignancy criteria:. Tumor histological pattern of "hemangiopericytic" variety could be reliably identified thanks to immunohistochemical procedure. PMID- 17338239 TI - [Comparative evaluation of data on combined and surgical treatment of cancer of the distal part of the stomach]. PMID- 17338240 TI - [Combined cytoreductive surgery and intraoperative hyperthermic chemo-perfusion for peritoneal carcinomatosis: methods, postoperative features and end results]. AB - Peritoneal carcinomatosis is detected in 10-40% of patients with "first look" peritoneal tumors. Median survival after chemotherapy is generally 2-6 months. Use of cytoreductive surgery and intraoperative intraperitoneal chemohyperthermic perfusion (ISHTP) improves the end results significantly. The study included 45 cases of surgery: gastric cancer (15), ovarian and cervical carcinoma ('17), colorectal cancer (8) and miscellaneous cancers involving advanced peritoneal carcinomatosis (5). ISHTP procedure was carried out immediately after cytoreductive surgery including peritonectomy (Sugarbaker). Postoperative complication and lethality frequency was 37.7 and 22.2%, respectively; mean survival--17 months. Eight patients have survived without signs of relapse; three of them--for more than 2 years. Cytoreductive surgery plus ISHTP protocol for peritoneal carcinomatosis increases survival time 3-fold and improves quality of life. PMID- 17338241 TI - [Role of Ki-67, mutated gene-suppressor p53 and HER-2neu oncoprotein in the prognosis for the clinical course of bladder cancer]. AB - A retrospective analysis included 63 patients with urothelial cancer. Untreated tumor tissue sampled in the course of primary surgery was examined by immunostaining procedure. After surgery, superficial tumors were treated with intravesical chemotherapy, invasive cancer--chemoradiotherapy. Overall survival was significantly higher in cases of low expression of antigen Ki-67 and gene suppressor p53 while relapse-free survival in patients without HER-2 expression was significantly higher than in cases of overexpression. PMID- 17338242 TI - [Correlation between size and localization of stage-pT adenocarcinoma of the prostate]. AB - According to the data on resected material sampled from 58 cases of radical prostatectomy, a relationship between size of adenocarcinoma and prostate and localization of the main tumor node, on the one hand, and pathological stage (pT) of primary tumor was established. Incidence of pT3 was dependent on tumor volume when adenocarcinoma was in the periphery of the prostate which involved the following relationships between pT, on the one hand, and tumor size and site, on the other: the closer tumor to the gland center, the lower the value of pT. Conversely, peripheral zone size showed the least variation in elderly men. Risk of pT3 appeared to be associated with small size of the prostate. Our findings may be used for identification of tumor size and pathology detection by means of biopsy prior to surgery. PMID- 17338243 TI - [Correlation between receptor status and results of treatment in endometrial carcinoma]. AB - In the course of immunohistochemical assay of estrogen (ER), progesterone (PR) and oncoprotein HER-2/neu receptors, PR+ expression was identified in 52% of 50 patients with endometrial carcinoma. A direct correlation between ER and PR levels (i = 0.7) was established (ER+/PR(+)--26.0%; ER-/PR(-)--42.0%; ER-/PR(+)- 26.0%; ER+/PR(-)--6.0%). In the ER+/PR+ and--ER-/PR+ groups, adjuvant therapy with progestins was carried out (3-year-survival--95.3% (p < 0.05)); recurrence rate--8.0%. Inverse correlations were characteristic of ER and HER-2/neu (i = 0.4) and PR and HER-2/neu (i = -0.114). Adjuvant polychemotherapy was administered in 12.2% of cases of HER-2/neu over-expression. That group revealed a drop in 3-year survival from 85.5 to 41.7% and relapse in half of the patients. PMID- 17338244 TI - [Immunotherapy of invasive cancer of the urinary bladder]. PMID- 17338245 TI - [Role of brachytherapy for radical treatment of prostate cancer]. PMID- 17338246 TI - [Potential of modern urology in palliation of cancer]. AB - The paper deals with certain issues in present-day oncology and introduction of the most efficient endourological procedures to improve quality of life. Most cancer patients suffer urological cancer-related and postoperative complications. Oncologists are often confronted with such problems as disturbed passage of urine in colorectal and gynecological cancers, radiation injury and surgery-induced impairment of the urinary tract and urolithiasis in cancer patients. Diagnostic and therapeutic potential of modern urology and novel approaches intended to improve quality of life in cancer patients with urological complications are discussed. PMID- 17338247 TI - [Use of radiofrequency ablation in palliative therapy of renal cancer]. AB - New methods in management of renal cancer promising better quality-of-life outcomes have been introduced for the past 10-15 years. They offer more opportunity of early detection of cancer, differential diagnosis and more accurate staging. Yet, there is a sizeable percentage of patients who cannot undergo surgery for general health reasons, multiple tumor involving both kidneys or involvement of a single kidney. Such patients may be given radio frequency ablation which causes a.c.-charged intracellular structures to vibrate leading to coagulation of tumor. Being unable of complete cure, the procedure is well tolerated. It gives the feeling of comfort, improves quality of life and is often followed by survival times comparable to postoperative ones. PMID- 17338248 TI - [Photodynamic therapy of superficial cancer of the urinary bladder to prevent relapse]. PMID- 17338249 TI - [Cost effectiveness of screening for prostate cancer]. AB - According to most experts, problems of prostate cancer (PC) have reached world wide social and economic resonance at the turn of the 21st century. Costly programs of diagnosis and treatment of generalized PC and its complications require most spending. The general demographic situation and increased aging of male populations, both worldwide and in this country, make it clear that the total costs of medical aid to PC patients will inevitably grow. However, programs of screening for PC can help. PMID- 17338250 TI - [Radioisotope lymphoscintigraphy used for precise diagnosis of metastatic lymph node involvement in localized and locally advanced prostate cancer]. PMID- 17338251 TI - [Cytologic diagnosis of hepatic tumors by examining puncture bioptates]. AB - Data on cytological diagnosis of hepatic tumors (1996-2006) are evaluated. The potential of cytological examination for identification of the biological mechanism and histological pattern of such malignancies were demonstrated. Cytological examination of puncture bioptates established such diagnostic features as sensitivity (90%), specificity (88%), and effectiveness (89%) as well as prognostic significance of positive (99%) and negative (41%) results. PMID- 17338252 TI - [Use of vitaflor to eradicate Helicobacter pylori in treatment of MALT-lymphoma of the stomach]. PMID- 17338253 TI - [Psychiatric mortality in cancer (a case)]. PMID- 17338254 TI - [Role of endobronchial methods in combined palliative treatment of lung cancer]. PMID- 17338255 TI - [Psychogenic death in oncology: validation, pathogenesis, development patterns and prophylactic potential]. PMID- 17338256 TI - [Indexes of modulating influence of gonadal hormones on ultrastructural characteristics of neurons of Amygdala's dorsomedial nucleus]. AB - The ultrastructure of neuron's perikaryons in Amygdala's dorsomedial nucleus of male and female rats at different stages of estrous cycle was investigated. The main functional stages were described. The characteristics obtained reflected the phenomenon of hormone-dependent functional reversion determined by changes in concentrations of sex steroids in blood. PMID- 17338257 TI - [Morphometrical analysis of endoplasmic reticulum dynamics in growing amphibian oocytes]. AB - Morphological analysis of endoplasmic reticulum (ER) dynamics was carried out in early amphybian oocytes at different stages of their development. Comparative morphometric analysis of ER membrane relative surface area and relative volume has shown that at the 1st-2nd stages of oogenesis the accumulation of ER membranes occurred mainly in the peripheral region of the cell cytoplasm. At the 3rd-4th stages of oocyte growth characterized by active transcription, the increase in the relative volume of ER and relative surface area of ER membranes occurs in the middle and near-nuclear region of cytoplasm, and reduction of these parameters takes place in the peripheral part of the cell. Simultaneously observed fusion of numerous ER vesicles with the outer nuclear membrane may serve as an evidence of active formation of new fragments of nuclear envelope. The 5th 6th stages of oocyte development are characterized by an increase in the relative volume of ER in the whole oocyte. It has been supposed that the revealed reorganization of endoplasmic reticulum in growing amphibians oocytes might be due to yolk accumulation (vitellogenesis), redistribution of calcium ions, and synthesis and storage of lipids and proteins. These processes are necessary for the future embryo development, and also for assembly of new fragments of growing nuclear envelope. PMID- 17338258 TI - [Endothelial ultrastructure of myocardium microvessels affected by various methods of artificial hypothermia]. AB - A comparative analysis of the endothelial ultrastructure of myocardium microvessels affected by various methods of artificial hypothermia was carried out. Tissue samples were harvested in children with a congenital ventricular septum defect after cooling the whole body under the conditions of hypothermic artificial circulation and perfusionless (immersion) hypothermia. It was found out that the shifts in population composition of endothelial cells, as well as the changes in the ultrastructure of organelles participating in endocellular syntheses and transendothelial transfer of macromolecules depended upon the rate body cooling. Under perfusionless hypothermia and of moderately low cooling rate, morphological signs of inhibition of endothelial cells metabolism were observed alongside with quantitative reduction of their micropinocytic transport indicators. Under hypothermic artificial circulation these reactions tended to lag behind due to the high cooling rate that initiates a heterogenic response of various endothelial processes to the changes of body temperature. PMID- 17338259 TI - [Dynamic analysis of modification of peripheral neutrophils functional activity and its regulation during tumor growth in vivo]. AB - Polymorphonuclear granulocytes (neutrophils) release the reactive oxygen species (ROS) for destruction of pathogens, providing quicker of an organism from infections and own defective of transformed cells. Reactive oxygen species are also potential carcinogens because they facilitate mutagenesis, tumor promotion and progression. Balance between these opposite influences is supported by coordinated interrelations in intracellular signaling systems. Tumor growth influence on the NADPH oxidase in peripheral innate immune cells is unclear. A solid cancer model was developed after an intramuscular injection of Ehrlich carcinoma cells into hind leg of NMRI strain mice. Intensity of the respiratory burst was estimated by luminol-dependent chemiluminescence technique. Transformation of inflammatory reaction was revealed during tumor growth: greater amounts of neutrophils were recruited into peritoneal cavity; sizes of the cells, their nuclei and granules were enlarged; the ratio of different cell types in peritoneal exudation was changed. The study revealed that tumor progression was accompanied by significant changes in functional activity of neutrophils. Dynamic increase in spontaneous level of ROS production and concentration-dependent change of intensity of the respiratory burst induced with chemotactic peptide N formyl-Met-Leu-Phe (fMLF) was revealed in peripheral neutrophils under tumor growth conditions. It was found that effects of inhibitors of tyrosine protein kinases, protein kinase C, mitogen-activated protein kinase p38MAPK (p38MAPK) and phosphatidylinositol 3-kinase (PI3K) were altered in neutrophils from tumor bearing mice in comparison with the cells of control mice. This indicates a change in the role of the enzymes in regulation of the neutrophil respiratory burst. Data obtained show that p38MAPK and PI3K entangle up- and down-regulation of NADPH oxidase in peripheral neutrophils during tumor growth. PMID- 17338260 TI - [Prolactin modulation of theophylline inhibitory action on maturation of bovine oocyte-cumulus complexes in vitro]. AB - The comparative investigation of the individual and joint impact of prolactin (PRL, 50 ng/ml) and theophylline (TP), a nonselective inhibitor of phosphodiesterases, on nuclear maturation of bovine oocytes and the expansion of cumulus cells enclosing the oocytes was carried out using a model of in vitro culturing. It has been shown that TP (5 mM) exerts a short-term inhibitory action on oocyte meiosis reinitiation and blocks it at diakinesis and metaphase I stages as well as inhibits the cumulus expansion. The addition of PRL to the medium containing TP caused the decrease in the rate of oocytes at diplotene stage after 6 h of culturing and the increase in the rate of oocytes attained the closing stages of maturation after 24 h of culturing. Furthermore, PRL suppressed partly the inhibitory impact of TP on the expansion of cumulus cells. The data obtained suggest the signal cascade induced by PRL in bovine oocyte-cumulus complexes to be compled with cAMP-dependent intracellular pathway. PMID- 17338261 TI - [The b chromosome polymorphism in Armenian and Turkey populations of the grasshopper Eyprepocnemis plorans plorans (Charpentier) (Orthoptera, Acrididae, Eyprepocnemidinae)]. AB - Karyotype analysis of the grasshopper Eyprepocnemis plorans samples derived from Armenian and Turkey populations was performed using C-banding technique. Chromosome polymorphism was associated only with B chromosomes that were revealed in all studied populations. Six new B chromosome morphotypes were described. Four morphotypes were found only in Armenian populations. One morphotype was revealed only in Turkey populations. One B chromosome morphotype was present in Armenian and Turkey populations. B chromosomes derived from Asian populations consisted mostly from C-positive regions. In some of the B chromosomes small C-negative regions were also registered. Morphotypes of the B chromosomes derived from Armenian and Turkey populations drastically differed from the B chromosomes described in the Iberian Peninsula and North African populations. In contrast to the B chromosomes from Armenian and Turkey populations the B chromosomes from Spain populations contained C-positive and C-negative regions alternated in their arms. PMID- 17338262 TI - [Altering of phragmoplast orientation as a result of excessive centrifugal movement in the absence of cell plate]. AB - The inability of phragmoplast to stop its centrifugal movement after reaching the mother cell membrane is described in abnormal meiosis with the arrest of cell plate formation. The excess of phragmoplast expansion leads to rotation of the whole telophase figure (phragmoplast with daughter nuclei) within the cell through 90 degrees. It has been suggested that this phenomenon may occur because of a the lack of signal stopping cytokinesis. Such a signal arises due to formation of daughter cell membranes. PMID- 17338263 TI - [The dynamics of Phanerozoic marine animal diversity agrees with the hyperbolic growth model]. AB - Generic diversity dynamics of the Phanerozoic marine animals is far better described by the hyperbolic model, widely used in demography and macrosociology, than by the exponential and logistic models from population dynamics traditionally employed for this purpose. Exponential and logistic models imply zero influence of interactions between taxa on the dynamics of diversity, with the exception of competing for unoccupied ecological space, whereas the hyperbolic model implies non-linear second-order positive feedback in the development of the biota. The hyperbolic human population growth is caused by positive feedback between population size and the rate of technological and cultural development (the more individuals, the more inventors, the more rapid progress, the more rapid growth of the Earth's bearing capacity; the smaller death-rate, the more accelerated growth-rate of the population). Probably there is also non-linear second-order positive feedback between diversity and community structure (the more genera, the higher alpha-diversity, which is defined as average number of genera per community, the more complicated and stable, "buffered" communities, the greater "taxonomic capacity of the environment" and average duration of the existence of genera; extinction rate dencreases, biodiversity growth-rate increases). The simplest mathematical model of biodiversity dynamics based on this assumption is confirmed by empirical data on alpha-diversity dynamics. Progressive complexification of marine communities during the Phanerozoic is also confirmed by the growing evennes of generic abundance distribution in paleocommunities. PMID- 17338264 TI - [Phylogenetic thinking in the modern biology]. AB - Any research activity is conducted within the framework of a cognitive situation which is defined by certain basic assumptions about ontology of the portion of the objective world under investigation. From the standpoint of the non-classical scientific epistemology, a part of that situation is constituted by personal knowledge which is formed by a set of thinking (cognitive) styles. The scholastic thinking existing in taxonomy and phylogenetics is considered as an example showing unavoidability of such styles in the natural history knowledge. It is initially rooted in the antic, mythological by its essence, persuasion of isomorphism between movements of the objective reality and of the mind. The instrumentalism entailed by scholastic thinking is based on the mythologeme according to which the "right method" par excellence can lead to the "right knowledge". That is why any disputes between different numerical methods of phylogenetic reconstructions are vain: their validity could be assessed not formally but within particular cognitive situations formed by particular basic models of the phylogenesis. Phylogenetic thinking is of the key importance in evolutionary biology and has great impact on various fields of biology based on it. It is pretty mythological because of non-observability of the phylogenesis: the latter is rather "thinked-in" in the objective world then is induced from the observed facts. It constitutes a part of the evolutionary thinking considering mainly macroevolutionary trends and stressing the initial causes in the structure of causal relations in the analyses of the diversity of organisms. The "tree thinking" of O'Hara is its rough operational equivalent. Relation between phylogenetic thinking and some other styles are considered, which are population, phenetic, typological, and epigenetic ("developmental" of O'Hara). Phylogenetic thinking makes it obliged inclusion of the initial causes in the explanatory models which underlie adaptive and functional peculiarities of organisms, as well as of the entire structure of the biodiversity. It manifests itself in such kind of models through uncovering the phylogenetic signal. This thinking style has great effect on understanding of the ontology of taxa and acknowledges the objective status of the phylogenetic pattern. It is intrinsically included in the argumentation schemes of constructional morphology, comparative phylogenetics. The central metaphor of the phylogenetics is the Tree of Life. Emagination of its unity and uniquiness is of naturphilosophical nature. From the contemporary epistemological standpoint, it should be considered as a generalization upon partial hypotheses of evolution of particular structures each corresponding to certain consideration aspect of the global phylogenesis. Acknowledging of multi aspectness of the phylogenesis constitutes one of the important points of modern phylogenetic thinking. As different semogeneses are incompletely congruent, the Tree of Life is less certain than each of the initial hypotheses. Any attempt to make it more resolved would lead to its reduction to any of the particular semogenetic scheme (i.e. to a "gene tree") or to its "decay" into several trees each corresponding to a particular consideration aspect of the global Tree. PMID- 17338265 TI - [Differentiation of radial glia cells into astrocytes is a possible ageing mechanism in mammals]. AB - Several obscure facts of gerontology are briefly reviewed. A attempt is made to shape new notions of the phenomenon based on the astrocyte hypothesis of ageing in mammals. This hypothesis interprets mammal ageing as a genetic disease with fatal outcome. The disease is caused by single character acquired by the theromorph lineage of the vertebrates in the course of evolution: the transformation of radial glia cells (RGC) into star-shaped astrocytes during the postnatal development, i.e. the disappearance of the fetal radial ways of nerve cell migration from proliferative zones to the sites of their ultimate localization in the brain of adult individuals. This process is the cause for the mammal brain being postmitotic. The disappearance of RGC induces a cascade of system processes termed age-dependent mechanism of self-destruction of mammals (AMSM). The disappearance of RGC inhibits the replacement of the nerve cells that have exhausted their living resources. Nerve cells are rigidly specialized and have restricted lifetime and ability of reparation. After some period, the level of homeostasis in nerve cells starts changing steadily for the worse due to irreversible pathological changes in the cells (especially in the neurosecretory cells). This brings damage to life-sypport systems of the mammal organism thus causing its death. The species-specific maximum life span is thus determined by the rate of metabolism in the organism. AMSM probably displays a general evolutionary principle: outer factors causing death (in non-ageing organisms) are replaced by inner factors. PMID- 17338266 TI - [The rithral macrobenthos community biogeography of southeastern Europe]. AB - The rithral and hypocrenal (of small rapid streams) macrobenthos faunas of northern Greece, eastern Carpathians, montane Crimea, and northwestern Caucasus are comparatively analyzed based on original material. Peculiarities of the rheophile communities and faunas of each region and of the whole studied area are described. The area is provisionally divided into biogeographic unites based on rithral fauna; this classification is essentially different from those of other authors. The main faunistic border runs meridionally between Greece-Carpathians on one side and Caucasus-Crimea on the other. The present authors believe that the biogeographic variability of macrobenthos rithral faunas results from the position of regions containing rithron communities and from spatial ties between them. Three fundamental biogeographic zones, suggested to be ranked as subregions, are recognized in the West Palearctic: the Balkan-Alpine (West European), the Scandinavian-Ural (North European), and the Caucasian. All the data available fit the suggested scheme, which shows that this approach is of universal value to biogeographic analysis and to divisions of the rithral into biogeographic zones. The local-scale variability of rheophile macrobenthos fauna in the northwestern Caucasus is discussed. Significant faunistic similarity of territories comprising the studied area is shown, internal division into biogeographic zones is conducted, and the lowest scale border of the faunistic diversity of rheophile macrobenthos is established at about 100-150 km. PMID- 17338267 TI - [Some problems of the study and representation of Siberian flora biodiversity in connection with its conservation]. AB - The present knowledge of flora of Siberia is quite insufficient, which is a considerable obstacle to the detection of its biodiversity for conserving the gene pool. Planning conservation measures should be focused not only on species, but also on intraspecific taxa and their phylogenetic uniqueness. In the absence of genetic data, available morphological and geographical methods should be used, so that, when it is impossible to establish the actual origin and relationship of taxa, the existing morphological diverstity is at least represented, as far as it is known to be based on genetic diversity. Phenetic maps can be of much use in the study of intraspecific morphological diversity. The estimation of geographic variability and morphological diversity, as well as the evaluation of territories, can be based on such maps. To represent adequately the biodiversity existing within poorly studied, presumably hybrid plant groups, until actual origin and relationship are known, they should probably be forcedly and provisionally considered as a special type of hybrid complexes, representing the unclear present day taxonomic situation. Such complexes could include populations and individuals with morphological characters of two or more different species, until the systematic position of such populations and individuals is further explored. Until the actual taxonomic status and relationship of the components are established, they could be regarded as subspecies permitted by the Code, or as certain recorded morphological deviations from the type, without assigning any taxonomic status to them--depending on the available data on variability and distribution. In the future, the resulting provisional information on morphological diversity would help to concentrate the efforts of biologists, in possession of the newest methods, on the most important objects, and serve as the scientific base for effective measures aimed at the conservation and management of the vast gene pool of the Siberian flora. PMID- 17338268 TI - Bactericidal activity of normal bovine serum (NBS) directed against some Enterobacteriaceae with sialic acid-containing lipopolysaccharides (LPS) as a component of cell wall. AB - The sensitivity of bacteria to the bactericidal activity of serum depends on the structure and organization of the bacterial outer membrane. Sialic acid has been found in the O-specific region of bacterial lipopolysaccharide (LPS) and it plays an essential role in protecting Gram-negative bacteria against the bactericidal activity of human and animal serum. The susceptibility of Gram-negative bacilli with sialic acid-containing LPS to the bactericidal action of normal bovine serum (NBS) was determined. The examined strains (Escherichia coli O104 (PCM 270), E. coli O24 (PCM 195), E. coli O56 (PCM 2372), Citrobacter braakii O37 (PCM 2346) and Salmonella enterica ssp. enterica serovar Toucra O48 (PCM 2359) showed variable sensitivity to the bactericidal effect of the serum. The role of the mechanisms of complement activation in the killing process was also determined. PMID- 17338269 TI - Characterization of coagulase-negative staphylococci isolated from cases of ostitis and osteomyelitis. AB - Coagulase-negative staphylococci (CoNS) are often responsible for cases of chronic ostitis and osteomyelitis, especially in patients with orthopedic prosthesis/implants. The aim of this study was to characterize CoNS isolated from ambulatory patients with chronic ostitis/osteomyelitis and to compare them by PFGE (pulsed-field gel electrophoresis). Out of 263 bacterial strains isolated from wounds/sinuses of patients with chronic ostitis/osteomylitis, 41 were identified as CoNS. Twenty methicillin-resistant strains were selected for this study. Our results confirm the superior performance of cefoxitin disk test to detect methicillin resistance in heterogenous population of CoNS. High level of antibiotic resistance was observed among the studied strains: majority of CoNS were resistant to tetracycline and erythromycin and also to clindamycin and ciprofloxacin. Importantly, in 15 out of 20 studied CoNS different phenotypes of macrolides, lincosamides and streptogramin--MLS resistance was suggested. Eight strains demonstrated resistance to both erythromycin and clindamycin, suggesting constitutive MLS(B) phenotype. Seven remaining strains presented resistance to erythromycin and susceptibility to clindamycin with negative D-test results, suggesting the presence of macrolides and streptogramines type A efflux pump. All studied strains were sensitive to vancomycin (MIC 0.75-2.0 microg/ml), teicoplanin (MIC 0.125-8.0 microg/ml), and quinupristin/dalfopristin (MIC 0.19 1.0 microg/ml). No clonal relatedness was observed in PFGE patterns. PMID- 17338270 TI - Bioactive compounds from Streptomyces nasri and its mutants with special reference to proteopolysaccharides. AB - The use of microbial exopolysaccharides (EPS) in the food, pharmaceutical, and chemical industries has steadily increased during the past decade. A bioactive EPS producing microorganism, Streptomyces nasri was isolated from Kuwait tropical soil and the proteopolysaccharide was tested for its antimicrobial activity. The isolate was subjected to ultraviolet (UV) radiation and acridine orange (AO) treatment to select for superior proteopolysaccharide producers. Among eight (five derived from UV exposure and three from AO exposure) morphological variants of Streptomyces nasri, two mutants showed increased EPS production, from 1.8 g/l to 2.3 g/l. The SDS-PAGE profiles of exopolysaccharides were determined. The molecular weight of the proteopolysaccharide ranged from 18 to 200 kDa. Mutants derived from UV exposure produced polysaccharides with higher molecular weight than those derived from acridine orange exposure. Acridine orange derived mutants produced lower molecular weight polysaccharides. Culture supernatants have been partially characterized and they show antimicrobial activity against a wide range of microorganisms. The structure of the exopolysaccharide was determined using NMR spectroscopy. The polysaccharide was also tested for cytotoxic activity against human brain tumor cell line using SRB assay. PMID- 17338271 TI - Hydrophobicity and biofilm formation of lipophilic skin corynebacteria. AB - Lipophilic corynebacteria isolated as natural flora of human skin were examined. Among 119 assayed strains 94% presented a hydrophobic cell surface and 75.6% were able to form biofilms. These attributes, as well as aggregation in liquid media, were statistically connected with each other and promote the developing of biofilms on solid surfaces. This was characteristic of all the lipophilic Corynebacterium species found on human skin that were examined in this study. C. jeikeium and CDC group G2 strains dominated in this population, and they could be responsible for investigated features in the whole lipophilic skin bacterial population. These two groups are the most common coryneform bacteria isolated from nosocomial infections and these attributes most likely promote them to cause opportunistic infections. PMID- 17338272 TI - Iron supply of enterococci by 2-oxoacids and hydroxyacids. AB - Only 9 (11.2%) out of 80 studied bacterial strains were able to utilize iron saturated 2-oxo acids and hydroxyacids and grow on o-phenantroline containing media. These strains belonged to Enterococcus faecalis and Enterococcus faecium species and were isolated from clinical material. Iron sources utilized by all of these strains were Fe(III) complexes with pyruvic, 2-oxobutyric, 4-methylthio-2 oxobutyric, 2-oxo-3-methylvaleric, 2-oxoisocaproic and 2-oxoadipic acids. None of the nine strains released 2-oxoacids to environment during growth in iron excess Fe+ medium and iron deficient--Fe- (Chelex) medium. In Fe- (phenantroline) medium, when the growth was strongly inhibited, only pyruvic acid was released. Iron uptake from 59Fe(III)-pyruvate was depended on iron deficiency during growth: cells harvested from Fe- (phenantroline) medium have acquired the most amount of iron. 2,4-Dinitrofenol was a strong inhibitor of 59Fe(III) iron uptake. Release of pyruvic acid is not subject to negative derepression and does not require the presense of iron as its inductor. It appears in the environment as a response to growth inhibiting stress caused by the iron deficiency but contrary to siderophores are not specially synthesized for iron assimilation. Therefore, it is only primary metabolism products released by damaged, but metabolic active cells. PMID- 17338273 TI - The growth, ferrous iron oxidation and ultrastructure of Acidithiobacillus ferrooxidans in the presence of dibutyl phthalate. AB - The iron-oxidizing bacteria Acidithiobacillus ferrooxidans is an example of strictly chemolitotrophic extremophile occurring in acidic environments. The prime niche of these microorganisms is an environment with low pH and high concentrations of iron, sulfide minerals or sulfur. Besides these environments, A. ferrooxidans is also isolated from heavy metal contaminated environments such as soil and sewage sludge and is known to be useful in bioremediation processes of these environments. In the current study, the influence of dibutyl phthalate on the growth, activity and ultrastructure of A. ferrooxidans ATCC19859 was shown. The presence of dibutyl phthalate in 9K medium did not influence A. ferrooxidans growth or ability to oxidize ferrous iron although changes in growth medium were accompanied by changes in the protein expression profiles of periplasmic fractions and remarkable changes in ultrastructure of the cell. PMID- 17338274 TI - Urea and ureolytic activity in lakes of different trophic status. AB - Urea and uraease (U-ase) activity were determined in water samples taken from the surface layers of 17 lakes of different trophic status. Urea concentrations were inversely correlated with the trophic status of the studied lakes and varied from below the detection limit to 25 micromol l(-1). Maximal potential ureolytic activity (V(max)) ranged from 0.2 to 7.0 micromol l(-1) h(-1). The highest urea concentrations and the lowest U-ase activities were recorded in the spring, whereas the lowest urea concentrations and the highest rates of urea hydrolysis were observed late in summer, during heavy phytoplankton blooms. Since in the majority of the Great Mazurian Lakes microplankton growth was limited by nitrogen supply, urea was an important N source for both auto- and heterotrophic planktonic microorganisms throughout the growth period. U-ase activity was mainly related to the seston. Only up to 25% of total activity could be attributed to free enzymes dissolved in lake water. In epilimnetic water samples the bulk of the ureolytic activity originated from seston-attached bacteria. However, a positive, statistically significant correlation between ureolytic activity and chlorophyll a (Chl(a)) concentrations suggests that phytoplankton may also be responsible for at least a some of the observed ureolytic activity in the highly eutrophic Great Mazurian Lakes. PMID- 17338275 TI - Characterization of selected groups of microorganisms occurring in soil rhizosphere and phyllosphere of oats. AB - Studies were carried out on the microflora of phyllosphere and soil rhizosphere of hulled (Chwat variety) and naked (Akt variety) oats. The material taken for study embraced samples of leaves and soil rhizosphere taken from cultivations differing in extent of nitrogen fertilization. The studies involved determination of total number of aerobic heterotrophic bacteria belonging to the genus Pseudomonas and microscopic hyphal fungi. Qualitative determinations focused on bacteria belonging to the genera Azotobacter and Azospirillum were also made. Our results point to differences in number of microscopic hyphal fungi in the phyllosphere of both varieties of oats, depending on nitrogen fertilization dose. However, there were no significant differences in the number of bacteria of the different genera determined in the phyllosphere and rhizosphere. Strains of oligonitrophilic and diazotrophic bacteria were isolated from samples of the phyllosphere of oats and their N2-fixing activity was determined by the acetylene reduction method using gas chromatography. PMID- 17338276 TI - A simple, direct plating method, alternative to dilution plating, for estimation of the abundance of Penicillium verrucosum on incubated cereal grain. AB - Because dilution plating is more labor intensive than direct plating, we would like to propose the use of a direct plating technique for estimation of Penicillium verrucosum abundance in cereal grain in incubation studies, with use of very selective and indicative for the fungus agar DYSG medium. The proposed method is based on the measurement of the diameter of P. verrucosum colonies grown around cereal kernels placed on DYSG medium. In three different experiments wheat grain contained a great range of P. verrucosum CFU number (from < 25 to 77 x 10(6) per 1 g). When P. verrucosum CFU number was at least as high as 10(2) per 1 g of the grain, 100% of the wheat kernels, placed on the surface of DYSG medium, were surrounded by colonies of P. verrucosum. The diameter (x, mm) of P. verrucosum colonies surrounding wheat kernels on DYSG medium was correlated with the fungal CFU number (y) on the wheat grain. The relationship is described by the exponential regression equation (y = 0.1258 e (0.9309x), R2 = 0.96). The relationship became linear (y = 0.404 x - 0.901, R2 = 0.96) after transformation of P. verrucosum CFU numbers to logarithms to base 10. PMID- 17338277 TI - L-forms of Staphylococcus epidermidis induced by penicillin. AB - L-forms of S. epidermidis were induced at 35 degrees C with the use of an L-form medium with penicillin. The aim of this study was to evaluate the frequency of L form induction and demonstrate whether the origin of the clinical strains affects the frequency of L-forms induction, as well as to study whether the time of action of the antibiotic has an influence on frequency of L-form induction. PMID- 17338279 TI - Effect of tetrahydrocurcumin on plasma antioxidants in streptozotocin nicotinamide experimental diabetes. AB - Clinical research has confirmed the efficacy of several photo-chemicals in modulating oxidative stress associated with diabetes mellitus. Here we investigate the effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on antioxidant status in streptozotocin-nicotinamide-induced diabetes in rats. A single dose of streptozotocin (65 mg kg(-1) bwt) resulted in decreased insulin, hyperglycemia, increased lipid peroxidation (thiobarbituric reactive substances, lipid hydroperoxides), and decreased antioxidant levels (vitamin C, vitamin E, reduced glutathione and ceruloplasmin). The oral administration of THC (80 mg kg(-1) bwt) for 45 days to diabetic rats significantly increased plasma insulin and plasma antioxidants and significantly decreased lipid peroxidation. The positive effects of THC were better that those achieved with curcumin. The results of the study indicate that in addition to its antidiabetic effect in type 2 diabetic rats, THC has an antioxidant effect. PMID- 17338278 TI - Biochemical aspects of lead exposure in silver jewelry workers in western Maharashtra (India). AB - This study was conducted to examine the effect of blood lead (Lead) on heme biosynthesis, the hematopoietic system, oxidative stress, and antioxidant status of silver jewelry workers (SJW) in western Maharastra (India). The blood lead level of the SJW group (N = 30) was in the range of 30.2-64.7 microg dL(-1) (mean +/- SD, 48.56 +/- 7.39 microg dL(-1)), whereas that of non-occupational Lead exposed normal healthy control subjects (N = 35) was 2.8-22.0 microg dL(-1) (mean +/- SD, 12.52 +/- 4.08 microg dL(-1)). Although the blood lead level of the SJW group increased significantly (p < 0.001) when compared with the control group, the urinary excretion of lead in the SJW group was not altered. In the SJW group, non-activated delta-aminolevulinic acid dehydratase (ALAD) activity significantly decreased (p < 0.05), and the ratio of activated/non-activated ALAD increased when compared with controls (p < 0.001), whereas activated ALAD activity was not altered significantly. Erythrocyte zinc protoporphyrin (ZPP) was not altered in SJW. The urinary excretion of delta-amino-levulinic acid (p < 0.001) and porpobilinogen (p < 0.05) of the SJW group increased significantly when compared with controls. Hematology parameters, such as the packed cell volume (p < .001) and total erythrocyte count (p < 0.05) significantly decreased, whereas the mean corpuscular hemoglobin concentration (p <.001) and total white blood cell count (p < .001) increased in the SJW group in comparison with controls. The serum malondialdehyde content significantly increased (p < .001), and the activities of antioxidant enzymes erythrocyte-SOD (p < .001), erythrocyte catalase (p < .05), and plasma ceruloplasmin (p < .001) significantly decreased in the SJW group compared with the controls. The results of the study clearly show an alteration of heme biosynthesis and cellular impairment of the pro-oxidants/antioxidants balance, resulting in oxidative damage in the silver jewelry workers group in western Maharashtra (India). PMID- 17338280 TI - The role of N-acetylcysteine treatment on anti-oxidative status in patients with type II diabetes mellitus. AB - The development of diabetic complications has usually been attributed to the nonenzymic glycation of tissue proteins. Only recently, however, have researchers examined the possible role on free radicals in the pathogenesis of diabetes. In the present study, glutathione (GSH) and major antioxidant enzyme levels in plasma of patients with type II diabetes mellitus were assessed both before and after 3 months of N-acetylcysteine (NAC) therapy. Thirty-two diabetic patients were examined as well as fifteen healthy controls. Before treatment with NAC, glutathione peroxidase (GPx), catalase (CAT), and (GSH) levels of diabetic patients and control subjects showed no significant differences, whereas glutathione S-transferase (GST) levels were higher in type II diabetic patients. Following 3 months of Following NAC supplementation, GSH, GST, and CAT levels were found to be similar to the levels before treatment. On the other hand, GPx activity was significantly lower compared with the values before treatment. According to this finding, NAC treatment could have a positive effect on GPx values in type II diabetic patients showing abnormally high values. PMID- 17338281 TI - Antioxidant potential of Biophytum sensitivum extract in vitro and in vivo. AB - An extract of the medicinal plant, Biophytum sensitivum (L.) DC (Oxalidaceae), was evaluated for its antioxidant potential in vitro and in vivo. Biophytum sensitivum was found to scavenge superoxide radicals generated by the photoreduction of riboflavin and hydroxyl radicals generated by the Fenton reaction and inhibited in vitro lipid peroxidation at concentrations of 50, 95, and 20 microg mL(-1) (50% inhibition [IC50]), respectively. The drug also scavenged nitric oxide (IC50 = 100 microg mL(-1)). The extract also induced the dose-dependant scavenging of nitric oxide in culture. Intraperitoneal administration of Biophytum extract inhibited superoxide generation in macrophages in vivo. The administration of B. sensitivum to mice significantly increased the catalase activity. The extract produced a significant increase in glutathione levels in blood and liver. The levels of glutathione-S transferase and glutathione reductase increased and those of glutathione peroxidase decreased after administering the Biophytum extract. The results of this study indicate that B. sensitivum has significant antioxidant activity both in vitro and in vivo. PMID- 17338282 TI - Changes in autoimmune markers of the anti-cardiolipin syndrome on days of extreme geomamagnetic activity. AB - The possible relation between various biological or medical phenomena and changes in environmental physical activity, such as Solar, Geomagnetic Activity (GMA); Cosmic Ray; Proton, and other particle flux, have been reported. These phenomena seem to be reflected, among others, in the immune system, resulting in changes in immunoglobulin (Ig) levels or outbursts of epidemics. AIM: to examine a possible association of GMA with another aspect of the immune system--autoimmunity. Fluctuations of levels of anticardiolipin (IgG; IgM, IgA subtypes) and lupus anticoagulant (Kaulin clotting time and Dilute Russell's viper venom time) autoantibodies, serving as anticardiolipin syndrome (ACLS) markers, were monitored during days of severe GMA storms and compared with those of lowest/quiet GMA days. Cosmophysical data were obtained from the NOAA National Space Service Center and the National Geophysical Data Center, USA. RESULTS: A significant rise in the levels of anti beta2Gp1-IgA (p = 0.0001); and KCT (p = 0.019) was observed on days of the GMA storms. CONCLUSION: On days of major GMA storms, significant changes in the autoimmune marker levels of ACLS were observed compared with quiet days. An involvement of those changes in clinical events related to GMA storms is possible. PMID- 17338283 TI - Effect of phenol on the metabolism and biochemical composition of the freshwater fish Cyprinus carpio. AB - The effect of phenol on the fish Cyprinus carpio and the metabolic changes in oxygen consumption and total carbohydrate, total protein and total lipids in the tissues of liver, gills, muscle, brain, and intestine were investigated for sublethal exposure. The oxygen consumption decreased significantly in both toxicants exposed to acute toxicity. Following sublethal exposure to phenol total protein, total carbohydrate, and total lipids in the tissues of liver, gills, muscle, brain and intestine of the fish decreased greatly. The longer the exposure time, the greater was the percentage reduction of organic matter of the fish exposed to sublethal concentration of phenol. Lipid content was not reduced much in exposure when compared with the control. PMID- 17338284 TI - Relaxation effect of estradiol on different vasoconstrictor-induced responses in rat thoracal artery. AB - This experiment was designed to compare the relaxant effect of estradiol on the contractions induced by 5-hydroxytryptamine, phenylephrine, and KCl in absence or presence of preincubation with the nitric oxide synthase inhibitor (NOS) N (omega)-nitro-L-arginine methylester (L-NAME). R at thoracic aorta contraction responses to vasoconstrictors were observed in the absence or presence of L-NAME. 17beta-Estradiol was added in increasing cumulative concentrations in the absence or presence of the L-NAME when the contractile response had reached a stable plateau. In the presence of L-NAME, 10(-6) M estradiol on precontracted 5 hydroxytryptamine rings caused significant relaxation in comparison with precontracted phenylephrine, KCl rings. In the presence of L-NAME, 10(-5) M and 10(-6) M estradiol doses on precontracted 5-hydroxytryptamine rings showed no significant difference in relaxation. The 10(-6) M, 10(-5) M, and 10(-4) M estradiol doses on precontracted phenylephrine caused concentration dependent relaxations. The results of this study show that acute vasorelaxation to 17beta estradiol is largely mediated via NO-independent pathways by inhibiting Ca+2 influx from the extracellular space and Ca+2 released from intracellular stores. PMID- 17338285 TI - Pay-for-performance: is medicare a good candidate? PMID- 17338286 TI - The three faces of retainer care: crafting a tailored regulatory response. PMID- 17338287 TI - Fluconomics: preserving our hospital infrastructure during and after a pandemic. PMID- 17338288 TI - Mortality, equality, and bioethics. PMID- 17338289 TI - The medical resident working hours debate: a proposal for private decentralized regulation of graduate medical education. PMID- 17338290 TI - Foreword: statistics in the analysis of arthritis data. PMID- 17338291 TI - Mean changes versus dichotomous definitions of improvement. AB - In recent years, when reporting the results of clinical trials for chronic disease, including rheumatologic conditions, use has been made of dichotomous definitions of improvement, but it is to be expected that continuous definitions would offer improved discrimination between treatment groups. Nevertheless, a well-constructed dichotomous outcome (usually a composite) has advantages of clinical sense and specificity and may, under a variety of realistic conditions, have power that closely approximates that of standard continuous outcome measures. This has been seen for established dichotomous outcome definitions for two rheumatologic conditions, rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Simulation studies performed using multivariate normal generated data that approximates actual trial data for each of RA and AS patients demonstrate the relative power of several dichotomous and continuous outcomes in realistic situations for each of RA and AS. Although the continuous outcomes are typically more powerful than the dichotomous ones, there are some situations in which the power of a well-defined dichotomous outcome approaches or even exceeds that of a continuous outcome based on mean change. PMID- 17338292 TI - Classifying radiographic progression status in early rheumatoid arthritis patients using propensity scores to adjust for baseline differences. AB - Various methods are used to measure radiographic joint damage in patients with rheumatoid arthritis (RA), but determining proportions of responsive patients is difficult. A key problem in observational studies when assessing damage outcomes is incorporating time to treatment initialization and adjusting for observed baseline differences. We examined five different definitions to select an appropriate index to classify radiographic damage in RA patients as progressive or nonprogressive. In addition, we compared different times from symptom onset to treatment and their effects on patient radiographic categorization. Propensity scores to adjust for baseline differences, including time since symptom onset, were used to match those treated early with those treated later using the stratification, radius, nearest neighbor and kernel methods. The mean effect of treatment on the treated was computed for each matching method. Observational data were analyzed for 185 early RA patients from the Western Consortium study followed six to sixty months (mean thirty-one months). For the selected index, 75 patients were categorized as nonprogressors; they had significantly lower disease activity, more clinical improvement and were treated earlier than the progressors. Of those treated within three months of symptom onset, 57% were classified as radiographically progressive versus 35% of those treated later (P = 0.0058). However, after propensity score adjustment for baseline differences, we noticed nonsignificant (P > 0.05) nonprogression in patients given earlier treatment. We conclude that propensity score analysis reduced but did not remove all bias. PMID- 17338293 TI - Assessing disease progression using a composite endpoint. AB - Scleroderma patients usually have serious medical events in several organ systems and it is desirable to have a composite index that accounts for disease activity in these organ systems. We show how one may use a composite 'time to event' analysis for evaluating such patients and more generally for patients suffering from a chronic disease. The composite 'time to event' analysis requires a composite endpoint with a Kaplan-Meier type analysis. As an illustration, we use data from a clinical trial for scleroderma patients and present sensitivity analysis where one or more of the organ involvement definition criteria are modified. In addition, we propose desirability functions to monitor patients' disease improvement when the outcomes are all continuous. This method offers several possible advantages over existing methods for measuring patients' improvement. PMID- 17338294 TI - Developing international consensus on measures of improvement for patients with myositis. AB - We discuss methods of developing consensus in measuring improvement in myositis. We consider selecting candidate variables, reliability and validity, percentage improvement/worsening rules, rules based on CART and logistic regression. We discuss criteria for determining an acceptable rule that include both numerical measures and physician acceptance. PMID- 17338296 TI - Influence of centrifugal force on filler loading of resin composites. AB - This study examined the influence of centrifugal force on the filler loading of composites using a light-polymerizing apparatus combined with a centrifuge. To assess uneven filler particle distribution resulting from specimen rotation, two low-viscosity composites (Palfique Estelite LV and Revolution Formula 2) were placed in test tubes, centrifuged, and subsequently light-polymerized with the apparatus. After each specimen was sliced into four disks (2-mm thickness), the inorganic filler content and Knoop hardness number (KHN) of each disk were determined. The results suggested that filler loading of composites could be increased by application of centrifugal force if the filler and monomer components were properly arranged. PMID- 17338295 TI - Analysis of chemical interaction of 4-MET with hydroxyapatite using XPS. AB - Each dental adhesive contains a specific functional monomer that determines its actual adhesive performance to tooth tissue. 4-methacryloxyethyl trimellitic acid (4-MET) is well-known as one of the functional monomers mostly available and consequently widely used in commercial adhesives. We therefore characterized the chemical interaction of 4-MET with hydroxyapatite (HAp) using X-ray Photoelectron Spectroscopy (XPS). XPS revealed that the peak representing -COO- of 4-MET shifted to a lower binding energy, when 4-MET was adsorbed onto HAp. Deconvolution of this shifted peak disclosed two components with a peak representing unreacted carboxyl groups and ester groups, and a peak suggesting chemical bonding of other carboxyl groups to Ca of HAp. XPS spectra of HAp treated with 4-MET also disclosed the surface to be enriched in calcium and decreased in phosphorus, indicating that phosphorus was extracted at a relatively higher rate than calcium. It can thus be concluded that true chemical bonding of 4-MET with calcium present in HAp occurred, as it was proven using XPS. PMID- 17338297 TI - Effect of thermocycling on interfacial gap-formation in Class V cavities and mechanical properties of spherical silica filler addition to resin-modified glass ionomer restorations. AB - The effects of thermocycling at 20,000 cycles and addition of silanized spherical silica filler (SF) on resin-modified glass ionomer cement (RMGIC) restorations were investigated. A RMGIC added with an untreated spherical silica filler (UF) was used as a comparison. Marginal gaps in Class V tooth cavities, compressive strength, diametral tensile strength, flexural strength, and shear bond strengths to enamel and dentin were examined. All thermocycled samples showed decreased frequency of marginal gap formation as compared to the 24-hour samples, with reduction of 73% to 95%. At the immediate condition, after 24 hours, and after thermocycling, the addition of 10 wt% SF yielded the most favorable results in terms of marginal gap formation in Class V cavities, compressive strength, flexural strength, and shear bond strength to enamel. Diametral tensile strength and flexural strength were also increased significantly by the addition of 5 wt% SF. Further, shear bond strength tests showed that the addition of SF had no effect on bonding capability to enamel and dentin. PMID- 17338298 TI - Effect of air-blowing variables on bond strength of all-in-one adhesives to bovine dentin. AB - This study evaluated the effect of air-blowing variables on the microtensile bond strength (microTBS) of two all-in-one adhesives. A bonding agent was applied to the flat dentin surface of extracted bovine teeth, and the surface left undisturbed for 20 seconds. Gentle or intensive air-blowing was applied for five seconds, and the adhesive photopolymerized for 10 seconds. Resin composite paste was placed and cured after each bonding treatment. Specimens were subjected to microTBS test with a crosshead speed of 1.0 mm/min. Data were statistically analyzed using ANOVA, followed by Bonferroni post hoc test. When Clearfil tri-S Bond was bonded to dentin, the microTBS value of specimens applied with intensive air-blowing was significantly higher than that applied with gentle air-blowing (p<0.01). On the other hand, with Fluoro Bond Shake One, the microTBS value of specimens applied with intensive air-blowing was significantly lower than that applied with gentle air-blowing (p<0.01). PMID- 17338299 TI - Effects of alumina-blasting and adhesive primers on bonding between resin luting agent and zirconia ceramics. AB - This study evaluated the effect of alumina-blasting and three commercial adhesive primers on the shear bond strength of a dual-cured resin luting agent to zirconia ceramics. Two different-sized zirconia ceramic specimens were treated with or without alumina-blasting and then treated with one of three adhesive primers. Subsequently, specimens were cemented together with Linkmax HV (GC). Half of the specimens were stored in water at 37 degrees C for 24 hours and the other half thermocycled 10,000 times before shear bond strength testing. For groups treated with either alumina-blasting or primer, shear bond strength significantly decreased after thermal cycling. For groups treated with both alumina-blasting and one of the three primers, there were no significant differences in shear bond strength before and after thermal cycling (p<0.05). It was thus concluded that the application of each of the three adhesive primers following alumina-blasting was effective for strong bonding of resin luting agent to zirconia ceramics. PMID- 17338300 TI - Micro-computed tomographic evaluation of a new enzyme solution for caries removal in deciduous teeth. AB - This study evaluated a new enzyme solution (SFC-V) for dentin caries removal, and obtained results were compared with Carisolv. Both solutions were used with a prototype plastic instrument - this being a modified technique for Carisolv. Five carious deciduous teeth were sectioned, and both treatments were applied alternately to each half. Micro-CT observations showed that both treatments resulted in removal of the outer demineralized dentin layer: 28.6% for SFC-V and 28.2% for Carisolv. As for the remaining demineralized dentin, thicknesses of 0.27 microm (SFC-V) and 0.31microm (Carisolv) were observed with no statistically significant differences. FE-SEM analysis revealed that the use of Carisolv resulted in a rougher surface; whereas after SFC-V enzymatic treatment, an organized dentin collagen network with open tubules and few signs of bacteria were observed. In summary, the experimental enzymatic solution and the modified Carisolv treatment removed comparable amounts of carious dentin but with differing resultant surface morphologies. PMID- 17338301 TI - Plasma-based fluorine ion implantation into dental materials for inhibition of bacterial adhesion. AB - The aims of this study were to evaluate the fluorine depth profiles of pure titanium (Ti), stainless steel (SUS), and polymethyl methacrylate (PMMA) modified by plasma-based fluorine ion implantation and the effects of fluorine ion implantation on contact angle, fluoride ion release, and S. mutans adhesion. Fluorine-based gases used were Ar+F2 and CF4. By means of SIMS, it was found that the peak count of PMMA was the lowest while that of Ti was the highest. Then, up to one minute after Ar sputtering, the presence of fluorine and chromic fluoride could be detected by XPS in the surface and subsurface layer. As for the effects of using CF4 gas for fluorine ion implantation into SUS substrate, the results were: contact angle was significantly increased; no fluoride ion release was detected; antibacterial activity was significantly increased while initial adhesion was decreased. These findings thus indicated that plasma-based fluorine ion implantation into SUS with CF4 gas provided surface antibacterial activity which was useful in inhibiting bacterial adhesion. PMID- 17338302 TI - Influence of novel resin monomer on viability of L-929 mouse fibroblasts in vitro. AB - We have previously synthesized a novel acrylic resin monomer, methacryloyloxyethyl methyl succinate (TA). The aim of this in vitro study, therefore, was to examine its influence on cell viability using L-929 mouse fibroblasts and then compare the results with MMA, EMA, and LMA. Medium containing each monomer was changed every 15 minutes as some monomers were volatile. After one hour of exposure, these mediums were replaced with a normal medium and cells were further incubated for 72 hours. IC50 value for each monomer was determined, and chronological cell viability and cytomorphologic observation were evaluated. Viability was impaired in a dose-dependent manner. All monomers, except TA, tended to correlate between molecular weight and cell viability. On the other hand, TA showed excellent viability and did not impair growth abruptly. These results thus demonstrated that cellular damage by TA was much lower than that by other monomers. PMID- 17338303 TI - Effect of ceramic coating by aerosol deposition on abrasion resistance of a resin composite material. AB - Aerosol deposition (AD coating) is a novel technique to coat solid substances with a ceramic film. The purpose of the present study was to investigate the effect of AD coating on abrasion resistance of a resin composite material. A 5 microm-thick aluminum oxide layer was created on the polymerized resin composite. The specimen was cyclically abraded using a toothbrush abrasion simulator for 100,000 cycles. Abraded surface was then measured with a profilometer to determine the average roughness (Ra) and maximum roughness (Rmax). It was found that abrasion cycling increased the Ra value of the No-AD-coating group, but decreased the Ra and Rmax values of the AD coating group. Moreover, the AD coating group showed significantly smaller Ra and Rmax values after 100,000 abrasion cycles as compared to the No-coating control group. Microscopic observation supported these findings. In conclusion, the resistance of the resin composite against toothbrush abrasion was improved by AD coating. PMID- 17338304 TI - Preparation and properties of chitosan/calcium phosphate composites for bone repair. AB - Chitosan/calcium phosphate (CaP) composites composed of bioactive calcium phosphate and flexible chitosan were made by a simple mixing-and-heating method. Phase composition, morphology, and mechanical properties--including in-air and in vitro fatigue behavior - were evaluated. Experimental results showed that the chitosan matrix did not affect the crystalline phase of CaP. However, the content of CaP additive affected the three-point bending strength of the composites. A CaP/ chitosan ratio of 5% by mass to volume in the composite achieved the significantly highest bending strength of 45.7 MPa. Stability of chitosan/CaP hybrid composites was apparently affected by in vitro cyclic loading. Nonetheless, when applied a loading stress of 11.4 MPa, the sample containing the optimal 5 mass/vol% CaP lasted 40 minutes in in vitro fatigue test until failure occurred. It was thus concluded that hybrid biocomposites with initial high strength might be a potential implant candidate for bone defect repair. PMID- 17338305 TI - Effect of thermal cycling on microleakage of a fissure sealant polymerized with different light sources. AB - The purpose of this study was to examine the effect of thermal cycling on microleakage of a fissure sealant after it was bonded with different bonding agents and polymerized with different light curing units. To this end, two bonding agents (Xeno III, iBond), three light curing units (Astralis 3, Elipar free-light, Elipar free-light 2), and a fissure sealant (Fissurit FX) were used. Microleakage was then evaluated using a dye penetration method after thermal cycling. When the fissure sealant was polymerized with Elipar free-light and Elipar free-light 2, microleakage at 10,000 cycles was significantly increased compared with that at 5,000 cycles. In terms of comparison among the curing units, the best microleakage score was observed with Astralis 3 (p<0.05). In terms of comparison between the two bonding agents, no significant differences in microleakage score were observed (p>0.05). Further, it was concluded that in order to evaluate microleakage scores appropriately, it was necessary for specimens to be subjected to thermocycling of 10,000 times or more. PMID- 17338306 TI - Preparation of carbon nanotube-alginate nanocomposite gel for tissue engineering. AB - A novel scaffold material based on an alginate hydrogel which contained carbon nanotubes (CNTs) was prepared, and its mechanical property and biocompatibility evaluated. Soluble CNTs were prepared with acid treatment and dispersed in sodium alginate solution as a cross-linker. After which, the mechanical property (elastic deformation), saline sorption, histological reaction, and cell viability of the resultant nanocomposite gel (CNT-Alg gel) were evaluated. The CNT-Alg gel showed faster gelling and higher mechanical strength than the conventional alginate gel. Saline sorption amount of freeze-dried CNT-Alg gel was equal to that of the alginate gel. In terms of histological evaluation and cell viability assay, CNT-Alg gel exhibited a mild inflammatory response and non-cytotoxicity. These results thus suggested that CNT-Alg gel could be useful as a scaffold material in tissue engineering with the sidewalls of CNTs acting as active sites for chemical functionalization. PMID- 17338307 TI - Accumulation of element Ti in macrophage-like RAW264 cells cultured in medium with 1 ppm Ti and effects on cell viability, SOD production and TNF-alpha secretion. AB - The adverse effect of Ti on body-defense macrophage is not well understood. The aims of this study were twofold: (1) to examine the intracellular accumulation of Ti element; and (2) to measure the cell viability, superoxide dismutase (SOD) production, and TNF-alpha secretion of macrophage-like RAW264 cells cultured for two days in medium with 1 ppm Ti prepared from acidic ICP Ti standard solution. PIXE analysis showed that element Ti was accumulated up to 7.3 ppm in RAW264 cells when cultured in the medium with 1 ppm Ti. Further, RAW264 cells cultured in the medium with 1 ppm Ti exhibited cell viability of about 60%, SOD production of about 180%, and TNF-alpha secretion of about 170% relative to those of control cells cultured in the medium without Ti. It was speculated that phagocytosis of minute Ti-containing complex (mostly TiO2) by macrophage caused oxidative stress and inflammatory reaction, leading to cell proliferation arrest and increased production of SOD and TNF-alpha. PMID- 17338308 TI - Femtosecond pulse laser-oriented recording on dental prostheses: a trial introduction. AB - The purpose of this study was to evaluate the feasibility of using a femtosecond pulse laser processing technique to store information on a dental prosthesis. Commercially pure titanium plates were processed by a femtosecond pulse laser system. The processed surface structure was observed with a reflective illumination microscope, scanning electron microscope, and atomic force microscope. Processed area was an almost conical pit with a clear boundary. When laser pulse energy was 2 microJ, the diameter and depth were approximately 10microm and 0.2 microm respectively--whereby both increased with laser pulse energy. Further, depth of pit increased with laser pulse number without any thermal effect. This study showed that the femtosecond pulse processing system was capable of recording personal identification and optional additional information on a dental prosthesis. PMID- 17338309 TI - [Evaluation of a new real-time PCR assay kit for quantification of human immunodeficiency virus RNA in plasma]. AB - We evaluated the use of COBAS TaqMan HIV-1 for highly pure system (COBAS TaqMan) recently developed as a second-generation quantification of human immunodeficiency virus type 1 (HIV-1) RNA. The linearity, sensitivity, reproducibility, and effects of possibly interfering materials were examined and results compared to those of AMPLICOR HIV-1 MONITOR Test version 1.5 (AMPLICOR) using 6 virus isolates that were all different subtypes. Excellent linearity was obtained at 1.67 x 10(2)-1.73 x 10(6) copies/mL (r2 = 0.991). Sensitivity was 40 copies/mL at a 100% hit rate. Intraexperimental CVs were 27.4-50.8%, and interexperimental CVs were 29.3-81.5%. Although COBAS TaqMan showed an excellent titer correlation with AMPLICOR (r2 = 0.960), mean titer obtained with COBAS TaqMan was 3.1 times higher than that with AMPLICOR (p = 0.002), and 7.1 times higher in a sample of subtype C, suggesting discrepancies in HIV-1 RNA quantification between the two kits. This point should be noted when AMPLICOR is replaced by COBAS TaqMan. PMID- 17338310 TI - [Clinical and bacterial analysis of pediatric urinary tract infection]. AB - We analyzed the clinical and bacterial backgrounds of 120 patients with pediatric urinary tract infection (UTI). Escherichia coli was the main pathogen recovered from 98 patients (81.7%). All causative agents isolated from 50 uncomplicated UTI cases were E. coli. Of 98 cases of E. coli UTI, 71 were treated with second generation cephems, whose therapeutic effect was equal to that of third and fourth-generation cephems. MIC50 and MIC90 (microg/mL) for E. coli were as follows: cefazolin :2, 4; cefmetazole: < or = 0.5, 2; and ceftazidime: < or = 0.25, < or = 0.25. Yearly decline in susceptibility was not observed, but MIC elevation for third generation cephems (< or = 2 microg/mL) including ceftazidime was seen in six isolates. Careful monitoring of susceptibility trends is therefore necessary for appropriate antimicrobial therapy. PMID- 17338311 TI - [Two cases of lung infection due to Mycobacterium shimoidei, with special reference to bacteriological investigation]. AB - Mycobacterium shimoidei (Tsukamura 1982) is an uncommon but widely distributed pathogen usually isolated from respiratory specimens. We report two cases of lung disease due to M. shimoidei and the associated bacteriological results. A 45-year old man (Case 1) admitted to National Hospital Organization (NHO) Miyagi Hospital, a 75-year-old man (Case 2) admitted to NHO Higashi-Hiroshima Medical Center were found in initial chest X-ray and thoracic computed tomography (CT) to have a tuberculosis-like cavity in the left apex (Case 1) and the right apex (Case 2). In Case 1, the patient was treated with isoniazid and rifampicin for one month and lesions showed a partial response. In Case 2, the patient responded favorably with rifampicin, ethambutol, streptomycin, and clarithromycin therapy. Mycobacteria were repeatedly detected in smear and culture from sputum specimens in both patients. Isolates were nonphotochromogenic and rough. Isolated colonies developed after two to three weeks on 2% Ogawa egg medium. Organisms grew on 2% Ogawa egg medium at 30, 37, 42, and 45 degrees C, but not 25 degrees C. Both organisms were susceptible to 500 microg of p-nitrobenzoate per mL and 5mg of sodium chloride per mL. Isolates were negative for niacin accumulation, nitrate reduction, semiquantitative catalase, 68 degrees C catalase, 3-day aryl sulfatase, iron uptake, and MPB64 antigen production, but positive for Tween 80 hydrolysis (5 and 10 days), acid phosphatase, and pyrazinamidase. Isolates had typical uv-HPLC chromatograms similar to M. shimoidei, demonstrating triple-peak clusters with peaks in the early cluster. 16S rRNA gene sequencing showed isolates to be consistent with Mycobacterium shimoidei. Based on composite characterization, isolates were identified as M. shimoidei. This is, to our knowledge, the third case of M. shimoidei infection reported in Japan. PMID- 17338312 TI - [Clinical utility of in situ hybridization for diagnosing respiratory tract infection and sepsis]. AB - We studied the clinical utility of in situ hybridization (Hybrisep) in diagnosing respiratory infection and/ or sepsis. Peripheral blood was taken from patients with respiratory infections and suspected sepsis for both routine blood culture and in situ hybridization, and focal samples including sputum, bronchoalveolar lavage, and central and thoracic catheter, were simultaneously examined for bacterial culture. Specimens numbered 46. The clinical diagnosis was 20 cases of septicemia, with 26 specimens diagnosed as respiratory infectious diseases including hospital-acquired pneumonia and pleurisy. Positive cases of in situ hybridization were seen in 19 specimens (41.3%) in all specimens, significantly higher than that in blood culture (17.4%). Respiratory infection showed a high positive rate in in situ hybridization. Interestingly, the bacterial pathogen detected by in situ hybridization was not always consistent with that taken from focal samples. Whether the pathogen isolated by in situ hybridization is accurate etiologically or diagnostically remains unknown, but our findings suggest a polymicrobial infection in patients with hospital-acquired respiratory infections. In situ hybridization thus provides important information on the etiological pathogen in different infectious diseases. PMID- 17338313 TI - [Development of O-serogroup serodiagnosis for patients with hemolytic uremic syndrome by Ec-LPS array]. AB - We extracted lipopolysaccharides from 58 O-serogroup strains of Escherichia coli with phenol-water for use as antigens for an Ec-LPS array. The Ec-LPS array was made by dot-blotting of E. coli LPS on PVDF membrane. Commercial anti-E. coli O serogroup antisera reacted with homologous O-serogroup LPS in Ec-LPS arrays. Convalescent sera of 6 patients with hemolytic uremic syndrome reacted strongly with O157 LPS when IgM and IgA antibodies in patient sera analyzed by Ec-LPS arrays. When IgG antibody was analyzed in this array, it was difficult to diagnose the O-serogroup because of the reactivity of patient sera against many O serogroup LPS. These results match those by ELISA and western blotting. Compared to these serological techniques, Ec-LPS array appears superior to ELISA and western blotting in cost performance, time performance, and technical complexity. PMID- 17338314 TI - [Usefulness of immunological detection of both toxin A and toxin B in stool samples for rapid diagnosis of Clostridium difficile-associated diarrhea]. AB - Toxin detection from stool specimens is critical for the diagnosis of Clostridium difficile-associated diarrhea (CDAD). In Japan, only two toxin detection kits targeting toxin A alone are commercially available. We evaluated ImmunoCard Toxin A & B (ImmunoCard), based on enzyme immunoassay for the rapid detection of both C. difficile toxins A and B in stool specimens, compared to a toxin A detection kit (Uniquick) and cytotoxin assay. C. difficile was also cultured from stool specimens and the toxin production type of C. difficile isolates was identified by PCR analysis. Compared to cytotoxin assay, ImmunoCard sensitivity was 86.2%, specificity 93.8%, positive predictive value 91.8%, and negative predictive value 89.4% (n = 146). Sensitivity was significantly higher than that of Uniquick (60.0%, p = 0.0016). ImmunoCard detected 90.6% of cytotoxin positive specimens with isolated toxin A-positive, toxin B-positive C. difficile strains (Uniquick; 67.9%, p = 0.008) and 70.0% of these with isolated toxin A-negative, toxin B positive C. difficile strains. Although ImmunoCard was slightly less sensitive than cytotoxin assay, it requires no special equipment and completes the entire test in up to 20 min. ImmunoCard thus appears very useful in the rapid diagnosis of CDAD in the clinical laboratory. Kits for the detection of both C. difficile toxins A and B should be immediately introduced into Japan to ensure the correct diagnosis of CDAD and infection control. PMID- 17338315 TI - [Current biosafety in clinical laboratories in Japan: report of questionnaires' data obtained from clinical laboratory personnel in Japan]. AB - To determine the status of biosafety in clinical laboratories in Japan, we conducted a survey using questionnaires on the biosafety of laboratory personnel in 2004. We obtained data from 431 hospitals (response: 59.5%). Respondents were 301 institutions (70%) having biological safety cabinets (BSCs). BSCs were held in 78% of microbiological laboratories, 7.9% of genetic laboratories, 2.7% of histopathological laboratories, and 1% or less at other laboratories. A clean bench in examination rooms for acid-fast bacilli was applied at 20 hospitals. We found 28 cases of possible laboratory-associated tuberculosis infection, 25 of which were associated with lack of BSC. Other risk factors were immature skills and insufficiently skilled eguipment operation. The frequency of rupture accidents during specimen centrifugation was 67% in dealing with blood and 9.7% in collecting acid-fast bacilli. Half or more accidents were related to inadequate sample tube materials. Technologists were shown to be working on blood collection in many hospitals (75%), and 1,534 events of self-inflicted needle puncture developed in the last 5 years. These results suggest that biosafety systems are woefully lacking or inadequate in clinical laboratories in Japan and must be established at the earliest possible opportunity. PMID- 17338316 TI - [Studies on Vibrio vulnificus infection: molecular epidemiology of environment derived strains and clinical isolates]. AB - To clarify the route and source of Vibrio vulnificus infection, we conducted molecular epidemiological investigation by DNA analysis of 355 environmental isolates (seawater-derived strain: 86, sea mud-derived strain:36, and oyster derived strain: 233) and 65 human clinical isolates, for a total of 420 isolates, using pulse field gel electrophoresis (PFGE), with the following results. 1. When DNA was cleaved with 2 enzymes, Not I and Sfi I, and subjected to PFGE, Not I DNA interpretation was 76.9%, and Sfi I cleavage was 97.9%, showing that Sfi I was superior in cleaving DNA of this bacteria. 2. Sfi I-interpreted strains were subjected to PFGE and migration patterns were analyzed by UPGMA, but close classification was not possible because similarity was low, this infectious disease clearly originated from multiple rather than a single-clone. In this cluster, we concluded that this infectious disease was acquired through contact between the environment and human beings and viceversa. We identified an assortment of clinical isolates and environment-derived strains among more than 89% of strain groups tested, none of which could be expected to have the same origin. We conclued DNA analysis on these two types of restriction enzymes using PFGE, but were unable to classify test results in detail due to the proliferation of migration patterns and low degree of similarity. PMID- 17338317 TI - [Studies of treatment for Haemophilus influenzae type b meningitis in children]. AB - We summarize 41 cases of bacterial meningitis in the last 11 years caused by Haemophilus influenzae. All isolates were serotype b strain (Hib). Initial chemotherapy was started with ceftriaxone (CTRX) in 22 cases, ampicillin plus cefotaxime (CTX) in 9, CTRX plus panipenem/betamipron in 5, and CTX in 2. Some 31 cases were treated mainly with CTRX. Although therapeutic antibiotics showed good susceptibility for isolates, 8 complicated cases (19.5%) occurred. Sequalae were observed in 7 (17.1%) but none were fatal. Five strains with elevated MIC of CTX (0.12 to 1 microg/mL) recovered after 2001, and 3 of 5 strains also showed elevated MIC of CTRX (0.12 to 0.5 microg/mL), but all were cured completely with CTRX. At present, no treatment failures due to antibiotic resistance have been observed, and CTRX remains suitable as initial therapy for Hib meningitis. A decline in susceptibility for third-generation cephalosporin against beta lactamase-nonproducing ampicillin-resistant H. influenzae is emerging, however, so it will be necessary to consider combination therapy with CTRX given the foreseeable trend in MICs. PMID- 17338318 TI - [Epidemiological survey of pneumococcus serotypes in pediatric patients with acute suppurative otitis media]. AB - To determine the distribution of Streptococcus pneumoniae serotypes isolated from patients under 6 years of age with acute suppurative otitis media, to calculate the serotype coverage of 7-valent pneumococcal conjugate vaccine, and to clarify trends in PCG-resistant Streptococcus pneumoniae, we conducted a one-year prospective study from April 2005 to March 2006 at 10 medical institutions in Hokkaido, Miyagi, Chiba, Tokyo, Kanagawa, and Mie, Japan. Specimens collected by tympanotomy or myringotomy numbered 856, and 691 strains were isolated from 599 specimens. Of these, 219 isolates (31.7%) were identified as Streptococcus pneumoniae and 201 met study requirements. The most common serotype was 19F (52 isolates, 25.9%), followed by 6B (30 isolates, 14.9%) and 23F (24 isolates, 11.9%). Seven-valent vaccine serotype coverage was 62.7%. The percentage of PSSP was 40.3%, PISP 42.8%, and PRSP 16.9%, resistant strains (PISP and PRSP) combined accounted for 59.7%. Seven-valent vaccine serotype coverage for PISP was 80.2% and PRSP 82.4%. PBP gene mutation was observed in 175 isolates (87.1%), including 70 of gPISP (34.8%) and 105 of gPRSP (52.2%). Gene mutation induced by macrolides was found in 176 isolates (87.6%). PMID- 17338319 TI - [Two cases of AIDS diagnosed by onset of interstitial pneumonia]. AB - Case 1: A 35-year-old man admitted for fever and respiratory failure during several weeks was found in chest computed tomography (CT) to have interstitial pneumonia, and the plasma beta-D-glucan level indicated Pneumocystis jiverocii pneumonia. Psoriasis from second-stage syphilis raised the suspicion of HIV infection. Serum anti-HIV-1 antibody proved positive and CD4-positive lymphocytes in peripheral blood were 18/microL. The man died despite treatment. Autopsy confirmed P. jiverocii pneumonia. Case 2: A 28-year-old man seen for a fever and respiratory failure was found in chest CT to have mild interstitial pneumonia. We checked for hypersensitivity pneumonitis, Mycoplasma pneumoniae pneumonia, etc. The plasma beta-D-glucan level indicated possible P. jirovecii pneumonia and immunodeficiency. Serum anti-HIV-1 antibody proved positive and CD4-positive lymphocytes in peripheral blood were 34/microL. The man was treated successfully, using trimethoprim with sulfamethoxazole for his interstitial pneumonia. His clinical symptoms were compatible with P. jirovecii pneumonia. P. jirovecii pneumonia with AIDS may present with more subacute or subtle symptoms than other immunosuppressive diseases, making it difficult to diagnose. Medical professionals should thus make it a point to familiarize themselves with AIDS prevention. PMID- 17338320 TI - [Two cases of meningitis caused by the same Haemophilus influenzae type B strain in a nursery at a 3-month interval]. AB - We present 2 cases of meningitis caused by the same Haemophilus influenzae type b (Hib) strain in a nursery at a 3-month interval. Causative agents isolated showed good susceptibility to beta-lactams and both patients recovered without any sequelae. Survey culture at each occurrence of meningitis showed 10 asymptomatic nasopharyngeal carriers. Oral rifampin was administrated to all staff and infants, but 2 carriers were found a month later from chemoprophylaxis. Pulsed field gel electrophoresis analysis showed that the two strains isolated from meningitis patients and 12 from asymptomatic carriers were apparently identical. When systemic Hib infection occurs in a nursery, other infants may be at high risk for secondary disease. It is difficult, however, to eliminate Hib carriage by chemoprophylaxis, indicating that Hib vaccination to prevent systemic Hib infection is necessary in Japan. PMID- 17338321 TI - [Two cases of HIV-1 acute infection with antibody negative by immunochromatography method]. AB - We found two cases of HIV-1 acute infection, confirmed by nucleic amplification test (NAT) and/or RT-PCR, with HIV-1 antibody negative by immunochromatography (IC) method but weakly positive by particle agglutination (PA) test. These cases suggested that IC method was less sensitive than PA test in the detection of acute infections. It is necessary to execute the post counseling that considers the possibility of the acute infection in public health centers and testing places where IC method is used for the screening test. It is also important to recommend taking the following re-examination after a certain period to a person who seems to have had a chance of infection in a short time before testing. PMID- 17338322 TI - [Glaucoma with high myopia (editorial)]. PMID- 17338323 TI - [Refraction and accommodation]. AB - The main purpose of ophthalmology is to improve the quality of vision by the recovery of visual function. Visual acuity, among the visual functions, is the most important factor. Decreased far vision is caused mainly by refractive errors, while decreased near vision is caused by accommodative insufficiency, especially presbyopia. REFRACTIVE ERRORS: The development of myopia may be influenced by both polygenic and environmental factors. Investigation of the mechanism of myopia has progressed based on the experimental animal models of myopia. The conventional treatments for refractive errors is spectacles or contact lenses, and new treatment includes phakic IOL, orthokeratology, and refractive surgery. There are also newly designed types of equipment to assess refraction and refractive elements. ACCOMMODATIVE INSUFFICIENCY: Presbyopia is mainly corrected using multifocal or progressive power spectacle lenses. Nowadays, bifocal and multifocal contact lenses and sometimes surgical treatment are used for presbyopia. Equipment for asthenopia has also been developed. PMID- 17338324 TI - [Changing aspects in continuing medical education]. AB - Self-directed learning based on adult education theory and self-assessment are necessary for continuing medical education. Self-directed learning is the process whereby the individual takes the initiative in diagnosing his learning needs and setting his own individual learning goals, showing clearly the human and physical resources, putting an appropriate plan into practice, and evaluating the learning outcome. Because self-assessment is the evaluation of the process where the individual confirms his actual learning, portfolio assessment is utilized for this purpose. In the continuing medical education program of the Japanese Ophthalmological Society, it is vital that the appropriate credit and recognition program keep up with the changes in adult education theory. Therefore, portfolio assessment is introduced for self-assessment. The Ophthalmic Pathology Slide Seminar is a model of medical education based on self-directed learning. PMID- 17338325 TI - [Visual field defects in high myopic glaucoma compared with moderate myopic glaucoma]. AB - PURPOSE: To demonstrate the visual field defects characteristic of high myopic glaucoma eyes. METHODS: Eighty-one high myopic glaucoma eyes (< or = -8 diopter(D)) and eighty moderate myopic glaucoma eyes(-3 D approximately -6 D) from patients under the age of 60 were enrolled in this study. Visual acuity, Mean Deviation (MD) of Humphrey visual field analyzer (HFA) central 30-2 program, and the pattern of central visual field defect especially at the early stage of glaucoma (MD > or = -10 dB) were compared between high and moderate myopic groups. RESULTS: HFA examination revealed significant differences in MD values between the high and moderate myopic groups (-11.8 +/- 8.9 dB and -8.4 +/- 6.9 dB, respectively, p = 0.02). Average logMAR visual acuity of the high myopic group was significantly worse than that of the moderate myopic group. The analyses of the pattern of visual field defects especially at an early glaucoma stage demonstrated that there was no specifically damaged area, such as cecocentral scotoma, in high myopic glaucoma subjects. The nasal upper area of the fixation point was the area most affected in both groups. CONCLUSIONS: High myopic glaucoma eyes demonstrated significantly lower MD and visual acuity compared to those of moderate myopic glaucoma eyes. However, at an early stage of glaucoma, no visual field defect characteristic of high myopia was observed. PMID- 17338326 TI - [Case of pigmentary glaucoma treated with medical therapy, laser treatment, and trabeculotomy]. AB - PURPOSE: To report a case of pigmentary glaucoma treated with medical therapy, laser treatment, and trabeculotomy. CASE: A 36-year-old man presented with the characteristic Krukenberg spindle on the corneal endothelial surface and heavily pigmented trabecular meshwork. He was diagnosed with pigmentary glaucoma and was initially placed on medical therapy which became less effective over time in controlling intraocular pressure (IOP). Ultrasound biomicroscopy revealing bilateral reverse pupillary block and laser iridotomy was performed in both eyes to eliminate irido-zonular contact causing pigment dispersion. However, argon laser trabeculoplasty (ALT) was subsequently performed in both eyes due to insufficient IOP control. The left eye responded well to ALT, and postoperative IOP has been 14-16 mmHg with medication. On the other hand, the right eye required selective laser trabeculoplasty for uncontrolled IOP after ALT. With little improvement in IOP control after laser treatment, the right eye eventually underwent trabeculotomy which resulted in long-term success in controlling IOP at about 16 mmHg and in preventing the progression of glaucomatous damage. CONCLUSION: Improvement in IOP control with trabeculotomy was confirmed in a case of pigmentary glaucoma with heavily pigmented trabecular meshwork. Further studies are needed for evaluation of the management of pigmentary glaucoma. PMID- 17338327 TI - [Case of corneally displaced malignant conjunctival melanoma]. AB - BACKGROUND: We studied the clinicopathologic characteristics in a patient with malignant conjunctival melanoma associated with corneal invasion. CASE: A 62-year old man had a small melanocytic lesion of the inferior palpebral conjunctiva. Previously he had undergone excisional biopsy and was diagnosed as having melanocytic hyperplasia without cytological atypia at an other hospital. He developed recurrence and was referred to us. The pigmentary lesion was observed in the entire inferior palpebral conjunctiva. Biomicroscopic examination revealed that there was a granular pigment lesion in the cornea. The patient was diagnosed as having conjunctival melanoma with corneal invasion and treated with orbital exenteration and chemotherapy in our hospital. Clinicopathologic tests revealed malignant melanoma cells invading through the bulbar conjunctiva and into the cornea. Ultrastructural study by electron microscopy of the pigmented tumor cells in the cornea showed several lobations of the nuclei, a large active-appearing nucleolus, and an aberrant granular melanosomal morphology. CONCLUSIONS: The infiltration of palpebral malignant conjunctival melanoma was limited to the epidermis of the cornea. PMID- 17338328 TI - [Medical record/electronic medical record]. PMID- 17338329 TI - [Developing the new Supporting System of Chronic Diseases using the internet]. PMID- 17338330 TI - [Diagnostic Guideline and Criteria for Sarcoidosis--2006]. PMID- 17338331 TI - [Most promising trends in research in the field of forensic medicine]. PMID- 17338332 TI - [Gunshot damage inflicted by a short shot from some special-purpose arms]. AB - Inlet damage to clothes material caused by point-blank shots from a special submachine guns Val, 9-A-91, sniper complex BCK-4 furnished with a soundless non flame shooting devices (SNSD) was studied in experiment. Specific features of the affection and shot products distribution (shape, size, topography, accumulation of soot metals, etc.) were specified which allow judgement about guns and range of shot. How SNSD construction and shot range influence the above characteristics is shown. A relevant case is reported. PMID- 17338333 TI - [Computer diagnosis of traumatic impact by hepatic lesion]. AB - A method of computer-assisted diagnosis of traumatic affection by liver damage (HEPAR-test program) is described. The program is based on calculated diagnostic coefficients using Bayes' probability method with Wald's recognition procedure. PMID- 17338334 TI - [Structure of the hypothalamic nuclei in a severe craniocerebral trauma]. AB - Large- and small-cell hypothalamic nuclei from 30 males who died of craniocerebral trauma were studied. Number of neurons at different stages of neurosecretory process was calculated in the large cell nuclei (supraoptic and paraventricular nuclei). Mean volume of neuron karyon (MVNK) was estimated in all the nuclei as a neuron function index. It was found that the proportion of neurons at different stages of the neurosecretory cycle is changed in large cell nuclei. This points to impaired synthesis of neurosecretion. Significantly increased MVNK of the neurons of paraventricular, arcuate and posterior nuclei was detected. The above evidence demonstrates activation of humoral hypothalamic regulation of the endocrine and immune systems. PMID- 17338335 TI - [Assessment of harm to the health in proximal hip fractures]. AB - The analysis of expert certification on isolated hip fractures has shown that some experts make errors of underestimation of harm to the health basing on the criterion "duration of health impairment". How to prevent such errors and to improve quality of forensic medical certification is proposed. Such measures will raise social value of medical forensic expertise. PMID- 17338336 TI - [Algorhythm of making forensic medical expert examinations by medical documents in obstetric-gynecological practice]. AB - Most of the suits brought against medical professionals concern obstetricians gynecologists. The experienced clinicians take part in commissions of experts to certify validity of diagnosis, treatment, operations, manipulations. Current state of obstetric-gynecological expertise is characterized. Algorithm of making obstetric-gynecological examinations is proposed. Criteria on forensic-medical assessment of medical care conducted in comparison with current standards of this care are formulated. PMID- 17338337 TI - [Forensic-medical examination of the effect of current synthetic detergents on the exhibits]. AB - A test for trace quantities of synthetic detergents on fabric is described in detail. Feasibility of detergents identification in the spots on the exhibits with thin-layer chromatography on silufol is shown and cases of such identification in biological material are given for illustration. Adequacy of the results is confirmed. Such investigation in forensic-medical practice will raise informative value of expert certification in cases when standard biological methods are unable to provide necessary precision. PMID- 17338338 TI - [The analysis of tiapride in cadaveric material]. AB - To optimize conditions of tiapride isolation from cadaveric organs, we compared the results of conventional methods by Stas-Otto, A.A. Vasilyeva and V.F. Kramarenko which provide tiapride isolation up to 50% and a new precise and reproducible method providing 60 +/- 2% tiapride isolation. Identification of tiapride isolated from cadaveric material was made with thin-layer chromatography and high performance liquid chromatography. The latter assay employed the method of external standard. The original techniques proposed identify and measure tiapride in hepatic samples in the presence of unidentified endogenic compounds. The techniques are rapid, selective, sensitive and reproducible. PMID- 17338339 TI - [Gas chromatography/tandem mass-spectrometry assay for trace amounts of 3' hydroxystanozolol]. AB - 3'-Hydroxystanosolol detection in biological fluids at pg levels by gas chromatography/tandem mass spectrometry is described. Gas chromatography/high resolution mass spectrometry results can be confirmed with gas chromatography/tandem mass-spectrometry. PMID- 17338340 TI - [Gas chromatography with mass-selective detector in testing blood for amitriptyline and nortriptyline]. AB - The article describes the method of simultaneous detection of amitriptiline and nortriptilin in cadaveric blood using gas chromatography with mass-selective detection. Preparation includes liquid-liquid extraction and derivation with trifluoroacetic anhydride. Nortriptilin threshold of detectability in the blood is 0.02 mcg/ml, amitriptilin one--0.05 mcg/ml. The range of detectability--0.05 3.0 mcg/ml for both compounds. Maximal error of the compounds detectability was under 12.9% for concentrations 0.10 mcg/ml and 10.6% for concentrations 2.0 mcg/ml. The method was tested on expert material in forensic chemical examinations. PMID- 17338341 TI - [Pathomorphological visceral alterations in sudden non-traumatic death of tourists in high mountains]. PMID- 17338342 TI - [Novel laboratory techniques in preparation and investigation of diatomaceous plankton]. PMID- 17338343 TI - [Historical relations between forensic medical professionals from Moscow and European countries]. PMID- 17338344 TI - [Clinical and X-ray characteristics of first detected intrathoracic lymph node tuberculosis in children]. AB - Sixty-two case histories of Moscow children aged 4-12 years, treated at the Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences, for first detected intrathoracic lymph node tuberculosis (ITLNT), were studied. Planned and prophylactic studies revealed the disease in 95.1% (including 66.1% after mass tuberculin diagnosis and 29% on examination for their contact). The disease was more commonly asymptomatic. Mild or moderate signs of the total disorder syndrome were prevalent in the clinical picture. In 56.5% of cases, a tuberculous process was detected in the phase of consolidation and calcinations. Among the patients with intrathoracic lymph nodal changes in the infiltration phase, the children with minor forms of ITLNT whose diagnosis was verified by computed tomography were 72.7%. The use of computed tomography in the diagnosis of ITLNT allowed one to make the fullest evaluation of changes in intrathoracic lymph nodes, including the groups of the anterior and posterior mediastinum. PMID- 17338345 TI - [Tuberculin susceptibility and Mycobacterium tuberculosis infection in children]. AB - Tuberculin susceptibility was studied from the Mantoux test with 2TE in 253 children aged 14 years and during all previous years of their life. Positive tests were recorded in 72.4% of cases; doubtful tests were in 6.7%, and negative ones in 20.9%. Infection was diagnosed in 33.9 +/- 2.9%. The annual conversion of tubercular tests was 2.2 +/- 0.05%. Positive Mantoux tests with 2TE caused by the administration of BCG vaccine were observed in 45.1%, in most cases, due to persistent allergy after neonatal vaccination. The authors convince of the necessity of regularly making a tuberculin test and qualitative tuberculosis vaccines when clinically indicated. PMID- 17338346 TI - [BCG ostitis in children: the epidemiological parameters of some regions of the Russian Federation]. AB - The incidence of BCG ostitis was studied by the data of questionnaires sent from 36 areas of the Russian Federation (RF). Particular emphasis is laid on 15 northwestern RF regions where an indepth study dealing with the 2000-2004 detection rates of postvaccination osseous complications was conducted. The mean incidence rate was 6.62 per 100,000 vaccinated persons with great data differences between the regions. The reasons for the detected differences and the perspectives of further studies of the epidemiological indices of the incidence of postvaccination osseous complications are analyzed. PMID- 17338347 TI - [Osteoarticular tuberculosis of the bones and joints in children: the present situation and prognosis]. AB - In 1990-2005, a total of 855 children aged 4 months to 17 years were operated on for tuberculous lesions of bones and joints in a specialized department for surgery of childhood osteoarticular tuberculosis, Saint Petersburg Research Institute of Phthisiological Care. Changes in the course of the disease, its structure, and epidemiological features are analyzed. The lines to determine the urgency of the problem of osteoarticular tuberculosis in children within the next few years are given. PMID- 17338348 TI - [The significance of parameters of the reservoir of bacillary patients with pulmonary tuberculosis in the assessment of tuberculosis epidemic situation]. AB - The author analyzes the tuberculosis epidemic situation in Russia, by using the traditional scheme accepted in Russia and the procedure based on the follow-up of bacillary patients with pulmonary tuberculosis. The proposed procedure enabled the author to ascertain the reasons for the decreased rates of normalization of the tuberculosis situation and to make an objective proposal to implement tuberculosis-controlling measures. The performed study has led the author to recommend a new form of calculating the abacillation index and of establishing the standard for the proportion (75-85%) of bacterial isolation in patients with new-onset pulmonary tuberculosis. PMID- 17338349 TI - [The prevalence of abdominal tuberculosis and the specific features of its detection]. AB - A hundred and thirteen case histories of patients with isolated and generalized forms of abdominal tuberculosis were analyzed. The patients' age was 15 to 79 years; there were 86 (76.1%) males and 27 (23.9%) females. The patients were admitted more frequently from other tuberculosis facilities (66.7%) and less frequently from general hospitals (33.3%). In 62 (54.9%) cases, abdominal tuberculosis showed a complicated course. The residents of Moscow and its region, predominantly the unemployed (85.8%), prevailed in the structure of detected patients with abdominal tuberculosis. In the period of 2001 to 2004, there was a rise in the incidence of new-onset abdominal tuberculosis, its rate increased from 4.4 (2001) to 8.3% (2004) of the total number of patients admitted to Moscow clinical hospital No. 7 for extrapulmonary tuberculosis admitted. This gives no way of considering this site of tuberculosis to be rare. In the structure of abdominal tuberculosis, its generalized forms were prevalent (86.7%), which was associated with the late detection of abdominal tuberculosis and the significant increase in the number of HIV-infected patients from 14.3 (2000) to 33.3% (2004). Abdominal organ lesions were more frequently observed in severe generalized pulmonary processes, such as disseminated (45.1%), infiltrative (18.6%) or fibrocavernous (15.9%) tuberculosis. An algorithm of diagnosis of abdominal tuberculosis and the rates of its detection by various studies are presented in the paper. Abdominal tuberculosis was diagnosed in 8.9% of cases by noninvasive comprehensive examination methods, in 18.6% by laparoscopy, and in most cases (57.5%) intraoperatively. In socially dysadapted persons, postmortem abdominal tuberculosis was detected in 15% of cases. PMID- 17338350 TI - [Sociomedical factors of survival in first detected patients with caseous pneumonia]. AB - To provide evidence for the association of survival in patients with caseous pneumonia with sociomedical factors, a group of 116 patients aged 18 to 65 years with this new-onset disease from the Samara Region was examined. The results of the study were statistically processed by the SPSS program version 10.0. It has been established that there are critical periods in the life of patients with caseous pneumonia. The critical period is an early period (month 1 of the onset of the disease) for alcohol abusers and, in addition to the early period, a later period (from 1 to 1.5 years) in non-abusers. Young persons with the preserved social status have better chances of surviving early in the disease. Passion for alcohol decreases a survival chance in patients with caseous pneumonia by 1.9 times. PMID- 17338351 TI - [Differential diagnosis of protracted purulent destruction-complicated pneumonia in patients with risk factors]. AB - There is some doubt upon the correct diagnosis in a third (136 (31.5%)/431) of patients (114 males and 22 females) admitted as having a diagnosis of protracted pneumonia. An algorithm of examination of patients with risk factors was developed for the differential diagnosis of different types of protracted pneumonia, including its destructive forms. The algorithm was used in the X-ray pattern of infiltrative changes unresolving within 2-3 weeks during nonspecific therapy. Hemoptysis was observed in 76 (17.6%). Its causes were bleeding granulations in 58 patients and aspirated bronchial foreign bodies in 36. Major diagnostic difficulties were presented by 18 (13.2%) patients out of the 136 patients in whom pulmonary changes were detectable as round foci with destruction. Differential diagnosis ascertained blocked abscesses (n = 6), tuberculomas with decay (n = 5), infiltrative destructive tuberculosis (n = 3), peripheral cancer with decay (n = 2), and bronchiectasis (n = 4). PMID- 17338352 TI - [The prevalence and course of arterial hypertension in patients with pulmonary tuberculosis]. AB - The specific features of essential arterial hypertension (AH) were studied in patients with active pulmonary tuberculosis (PT) and in those with residual changes (RC) after prior PT. The prevalence of AH was defined in patients with PT in relation to age, gender, and clinical form of a tuberculous process. The study indicated that the prevalence of AH among patients with an active tuberculous process was less than in the general population and it amounted to 18.2%. It was more common in males aged less than 60 years and in females aged above 60 years. The prevalence of AH in fibrocavernous tuberculosis was less than that in other forms, which was associated with the impact of intoxication on blood vessels. The patients with RC after prior PT had more frequently AH than those with an active tuberculous process, as well as target organ changes and a severer course of AH. PMID- 17338353 TI - [Differential diagnosis of pulmonary tuberculosis and community-acquired pneumonia]. AB - The purpose of this investigation was to enhance the efficiency of differential diagnosis of pneumonia and pulmonary tuberculosis. A hundred and fifty-nine adult patients were examined. These included 78 patients with pulmonary tuberculosis and 81 with community-acquired p neumonia. The clinical features of infiltrative pulmonary tuberculosis (n = 48) and mild community-acquired pneumonia (n = 51) were compared. The course of caseous pneumonia (n = 30) was compared with that of moderate and severe community-acquired pneumonia (n = 30). Significant differences in the manifestations of the intoxication and bronchopulmonary syndrome were not found in patients with community-acquired pneumonia and infiltrative pulmonary tuberculosis. Physical studies showed that in patients with community-acquired pneumonia, moist rale (54.9%) and crepitation (11.8%) were prevalent, but in those with infiltrative tuberculosis rale was absent in 60.4% of cases and the pattern of respiration was unchanged in 79.2%. Chest X-ray studies indicated that in patients with community-acquired pneumonia, lower lobar inflammatory changes were predominant in 62.8% of cases whereas in those with infiltrative pulmonary tuberculosis the process was mainly bilateral (43.8%) with the presence of destructive changes (83.3%) and bronchogenic dissemination (66.7%). In patients with caseous pneumonia, the intoxication syndrome was more significant than in those with severe community-acquired pneumonia. Chest X-ray studies demonstrated that in patients with caseous pneumonia, specific changes were bilateral with the involvement of 2 lobes or more, with destruction and bronchogenic dissemination while in those with community-acquired pneumonia, the pulmonary processes were predominantly bilateral (76.6%) at the lower lobar site (36.7%). PMID- 17338354 TI - [Recurrent tuberculosis in the Sverdlovsk Region]. AB - In 2000 to 2005, there was a 1.8-fold increase in the rate of early recurrences and a 1.6-fold decrease in late recurrences in the Sverdlovsk Region. In the prisoners, early recurrences were 21 times more frequently observed than in the general population, which make up a significant majority of all the recurrences of tuberculosis. In conclusion, during preventive examinations, recurrences are mainly detected with earlier forms of tuberculosis as compared with the recurrences recorded in the municipal entities of the region. In adult males, the rates of primary morbidity were 3.2 times higher in adult males than in females; those of early and late recurrences were 8.1 and 5 times higher, respectively. In adults aged 18-44 years, the rates of primary morbidity and early recurrences of tuberculosis were 1.7 times higher than those in the persons aged 45 years or more; those of late recurrences were 1.6 times less. PMID- 17338355 TI - [Clinical features of female genital tuberculosis in the period of 1980 to 2005]. AB - Comparative analysis of two groups of patients with female genital tuberculosis treated at the Saint Petersburg Research Institute of Phthiosiopulmonology in 1980 to 2005 has shown that patients of younger age have recently fallen ill with this disease. The genital tuberculous process is commonly preceded or attended by other forms of tuberculosis of various organs and systems, such as the lung, lymph nodes, and kidney. The pain syndrome and impaired menstrual cycle are observed in half the patients; infertility is present in 60%; profound anatomic changes are less frequently seen in the fallopian tubes. Improvement of bacteriological methods promoted the timely diagnosis of the disease. PMID- 17338356 TI - [Neurorehabilitation in myelopathies caused by tuberculosis-induced ostitis and other diseases of the vertebral column]. AB - An algorithm of stepwise neurorehabilitation has been developed for patients with vertebrogenic myelopathy. The algorithm is constructed as a hierarchy of parallel and series tasks to recovery movement capacities of a paralyzed patient. Their solution requires the use of original procedures, such as initiation of locomotor activity by dermal and epidural spinal cord electrostimulation, propriospinal stimulation, dynamic vertical posture training, as well as treadmill therapy, tetrapedal walk, and therapeutic exercises. Neurorehabilitative treatment by the proposed algorithm was performed in 41 patients with vertebrogenic myelopathy, including 41 patients with clinically complete plegia. In baseline complete plegias, recovery of varying degree or compensation of locomotor capacities was achieved in 71% of the patients, in incomplete plegias, improvement of motor function was observed in all the patients. PMID- 17338357 TI - [Infiltrative tuberculosis and lung cancer]. AB - Concomitance of infiltrative tuberculosis and lung cancer cannot be considered to be rare and sporadic. Thirty-seven patients with concomitance of these two diseases were followed up at the phthisiosurgical department of the Kostroma regional tuberculosis dispensary in 1979 to August 2005. Uni- and bilateral tuberculosis affliction occurred in 14 and 23 patients, respectively. Thirty-four cases developed cancer in the lung that exhibited tuberculous changes. In this group of patients, the central form of cancer prevailed over the peripheral one (33 versus 4 patients). Stages I, II, III, and IV cancer were established in 1, 3, 22, and 11 patients, respectively. Eleven patients were operated on. PMID- 17338358 TI - [Drug-resistant tuberculosis in adolescent: clinical features, therapeutic effectiveness, long-term results]. PMID- 17338359 TI - [Hospital-substituting technologies in the diagnosis of primary malignant neoplasm and patients' preparation for surgical treatment]. PMID- 17338360 TI - [The experience of organization of medical care rendered to the Internal Affairs staff and Internal troops servicemen on a contractual basis]. PMID- 17338361 TI - [The treatment of extremity bone fractures in the cases of combined injuries]. AB - The experience of treatment of 76 injured with fractures of two or more extremities in combination with affection of other anatomical areas (head, abdomen, breast, pelvis) was summarized. The extrafocal osteosynthesis was preferable because this method is characterized by low traumatism, minimal blood loss, adequate reposition, stable immobilization and possibility of early load in the apparatus of external fixation. Immersed osteosynthesis is used with great caution as it can cause the development of fat embolism. One-stage operations were performed in 26.3% victims. Their treatment periods were significantly shorter than during the multi-stage operations. One-stage operations for polytrauma have the following advantages over the multi-stage operations: single narcosis, simplified treatment in reanimation department, one post-operation period, quick rehabilitation and economic benefit. The extrafocal osteosynthesis causes less purulent complications. PMID- 17338362 TI - [The incidence of stomatologic diseases among the reserve officers: the epidemiological investigation]. AB - The epidemiological study of the incidence of stomatologic diseases was conducted in 1030 reserve officers. The high level of stomatologic diseases among them was detected. The high incidence of diseases is characterized by the following indices: dental caries constitutes 100% with its intensity 14.15 +/- 0.22, parodontium diseases--92.87% (gingivitis--17.66%, parodontitis of mild and moderate degree--12.9%, of severe degree--62.30%), oral mucosa injuries--0.49%, not carious dental injuries--32.14%. 40.29% pensioners of RF Defense Ministry required prosthetics and 55.73%--oral sanitation. The results obtained could be used in scientific substantiation of medical standards, which are necessary for providing the reserve officers with dispensary method (active call) and development of recommendations to improve the staff structure of military medical and-prophylactic institutions and subdivisions of stomatologic profile. PMID- 17338363 TI - [Sildenafil influence on the level of pulmonary artery pressure, bronchial patency and endothelial function during the action of risk factors for development of cardiorespiratory pathology]. PMID- 17338364 TI - [The predictive value of intraocular pressure initial level for the early post operation period in the patients with primary open angle glaucoma]. PMID- 17338365 TI - [The peculiarities of diagnosis and treatment of chronic venous insufficiency and venous forms of lower extremity dysplasia]. AB - The authors present the modern viewpoint concerning the problem of chronic venous insufficiency in the cases of venous forms of dysplasia. The treatment of patients with of venous forms of dysplasia should be based on the principles of interdisciplinary approach, which stipulates both the careful diagnosis on the basis of mainly non-invasive methods and integration of surgical and conservative treatment methods. Today such treatment should be combined and conducted within the multi-purpose highly specialized institution. Only the combination of all treatment methods will allow achieving the best functional and esthetic results. In the cases when indications are absent and conduction of surgical or any other treatment method is impossible it is necessary control the venous anomaly (dynamical follow-up, compression as a basic variant of conservative therapy). It will allow minimizing the unfavorable influence on vital functions and improving the patient's life quality. PMID- 17338366 TI - [An outstanding organizer of military medicine (devoted to the 130th anniversary of Z. Solovyev's birth)]. PMID- 17338367 TI - [From Desna to Oka, from Protva to Ugra... (devoted to the 65th anniversary of Moscow battle)]. PMID- 17338368 TI - [Development of medical-and-prophylactic science in the Red Army during 20-30S of the XX century]. PMID- 17338369 TI - [The problems of troops medical support in general M. Skobelev's activitities]. PMID- 17338370 TI - [An enthusiast of military psychiatry]. PMID- 17338371 TI - [The military education in Sechenov Moscow medical academy is 80 years]. PMID- 17338372 TI - [The Ryazan garrison hospital is 75 years]. PMID- 17338373 TI - [Target-cell susceptibility and lung phagocyte activity in mice with influenza virus resistance lowered by glucocorticoidal immunosuppression]. AB - The results of the study showed that subcutaneous kenalog (Kn) lowered the resistance of mice to influenza virus (InV), as was seen by a decrease in 50% lethal dose and an increase in the degree of pulmonary tissue lesion, and the susceptibility of the lungs to InV, seen by the fact that 50% aerogenic infective dose (AID50) was significantly higher in the main group (Kn+InV) than in controls, which received Hanks solution subcutaneously (HS+InV). In vitro, 50% infective doses of InV for suspension of pulmonary and tracheal cells, characterizing their susceptibility to InV, were similar in Kn mice and controls. At the same time, lower resistance and higher degree of pulmonary inflammation noted in Kn mice after receiving a dose of InV that was much higher than an infecting one, was accompanied by the prevalence in the number as well as phagocyte and superoxide-producing activity of neutrophiles (Nph) over the same parameters for alveolar macrophages (AMph) as early as two days after receiving InV dose, vs. InV-infected controls. Evidently, one of the reasons for lower resistance to InV after Kn administration is significant disbalance between the functional activity of AMph and Nph populations. Ineffective AMph clearance of the lungs from InV and excessive number of recruited Nph and products of tissue disintegration may favor the development of respiratory failure and infectious toxic shock, which leads to lower resistance in animals which receive Kn before InV infection. PMID- 17338374 TI - [Genetic markers of predisposition to an aggressive course of chronic C hepatitis]. AB - The polymorphism of cytokine genes (11-1beta, IL-10, IL-6, and TGF-beta1) in patients with chronic C hepatitis and in healthy individuals was studied. The study found that the polymorphism of IL-1beta, IL-6, and TGF-beta1 may at least partially explain the genetic predisposition to an aggressive course of the disease with the development of terminal stage. PMID- 17338375 TI - [The mechanism of interaction between Yersinia pestis and erythrocytes, and its importance for the pathogenesis of plague]. AB - The ability of Yersinia pestis to get inside human and murine red blood cells (RBC) was found both in vivo and in vitro experiments. Due to oxidase and catalase activities, the microorganisms induced the denaturation of hemoglobin (Hb) through RBC oxidation to H2O2 in high concentration providing the formation of haemin and transformation of haem Fe2+ into the utilizable form, Fe3+. This phenomenon was found to be common in vitro for all Y. pestis strains used in the study independently of Pgm phenotype and plasmid content, including vaccine Pgm( ) Y. pestis EV NIIEG and plasmidless Pgm(+) Y. pestis PKR-133 stains. This, probably, allows the bacteria to use Hb as an essential source of iron and porphyrins for de novo synthesis of DNA followed by effective multiplication in the mammalian organism. A correlation between the loss of the ability of RBC to transport O2 to organs and tissues and the development of progressive tissue hypoxia with specific clinical features of metHb accumulation and haemorrhagic syndrome was shown. The participation of Y. pestis phospholipases (A and D) in the destruction of RBC membranes and translocation of plague bacilli into RBC, as well as the phenomenon of polysaccharide chain lengthening depending on cultivation conditions of Y. pestis bacteria, are discussed. PMID- 17338376 TI - [Cases of West Nile fever in Novosibirsk region in 2004, and the genotyping of its viral pathogen]. AB - Three cases of West Nile fever were registered for the first time in Novosibirsk region in 2004. The diagnosis was confirmed by revealing IgG against West Nile virus (three cases) and viral RNA (two cases). Sequence analysis of fragments of E protein gene showed that the virus belonged to Ia genotype. PMID- 17338377 TI - [Detection of cytomegalovirus antibody activity in intravenous preparations of immunoglobulins with parallel-line method]. AB - The study demonstrated a possibility to detect specific anti-CMV antibody activity in intravenous preparations of immunoglobulins by qualitative immunoenzyme analysis using parallel-line method. Independently of production technology, specificity, and the activity level, the preparations had a dose response curve that was parallel to that of a standard sample with five-point linearity at double-step dilution. This makes it possible to use the test system DS-ELISA-ANTI-CMV-G to detect anti-CMV antibody activity in ready-for-use preparations. PMID- 17338378 TI - [The use of P300 event-related potentials in the evaluation of the effectiveness of therapy of episodic exertional headaches]. AB - Fifteen healthy individuals and 17 patients with episodic exertional headaches were examined before and after treatment with citalopram using P300 event-related potentials. Unlike healthy controls, patients with headaches before treatment displayed an increase in P300 amplitude and the loss of its habituation, which correlated with a decrease in cognitive functions. The treatment lowered the degree of pain and vegetative syndromes, normalized P300 parameters, and improved cognitive functions. The use of P300 method may be an additional criterion of the effectiveness of therapy in patients with exertional headaches. PMID- 17338379 TI - [Interrelation between personal characteristics of students and the successfulness of their training]. AB - The main individual and typological personality characteristics of 246 female and 120 male students were determined with psychological tests. The results were compared to the measure of the successfulness of their training, determined as the mean score of the three last exam sessions. In both groups, failure-avoidance motivation dominated in 62% of students, while success-achievement motivation dominated in 37% of students. Factorial and other kinds of analysis, differentiated according to sex and this index, make it possible to associate the degree of successfulness on the exam with the typological characteristics of students according to extraversion-introversion and neurotism indices. PMID- 17338381 TI - The midwife: an endangered species. PMID- 17338380 TI - [The main tasks concerning the organization of surveillance and prophylaxis of HIV-infection in Russian Federation]. AB - The main task concerning striving against HIV/AIDS epidemic is effective use of present political, financial, organizational, and informative possibilities. However, despite efforts, the epidemic situation with HIV/AIDS is constantly worsening. Approaches to and stereotypes of the organization of this work and its fulfillment cannot provide a complete solution to this problem. Among strategic tasks that should be fulfilled at the federal level are the following: strengthening of coordination of actions from the departmental level to interaction with Russian and international organizations and the community of people living with HIV/AIDS; determination of requirements and purchase of necessary diagnostic test systems for HIV-infection detection as well as pharmaceuticals, and providing subjects of Russian Federation with them. Tactical tasks that should be fulfilled at the level of subjects of Russian Federation are the following: medical aid to patients with HIV/AIDS should become more approachable; complete dispensary observation and treatment of these patients should be organized. Civil society and interaction between non-profit organizations and governmental structures play an important role in organization and fulfillment of striving against HIV epidemic. PMID- 17338382 TI - Conservatives put midwives centre stage. PMID- 17338383 TI - This year's pay claim. PMID- 17338384 TI - Campaign for normal birth. Trust and expertise. PMID- 17338385 TI - FGM: an outmoded practice? PMID- 17338386 TI - Blood loss, replacement and belief. PMID- 17338387 TI - Focusing the group. PMID- 17338388 TI - A young mothers' midwifery scheme. PMID- 17338389 TI - The right kind of help. PMID- 17338390 TI - A pathway to normal labour. PMID- 17338391 TI - How things change... PMID- 17338392 TI - Staffing levels 'unsafe', NM survey finds. PMID- 17338393 TI - Learning the ropes. PMID- 17338394 TI - On the learning curve. PMID- 17338395 TI - Joining forces. PMID- 17338396 TI - Making all the pieces fit. PMID- 17338397 TI - Ten steps to staff motivation. PMID- 17338398 TI - The team wheel. PMID- 17338399 TI - Networking for nurses. PMID- 17338400 TI - Leadership for service improvement. PMID- 17338401 TI - [Photoeffects, Einstein's light quanta and the history of their acceptance]. AB - It is generally supposed, that the discovery of the efficacy-quantum by Planck was the impetus to Einstein's hypothesis of lightquanta. With its help Einstein could explain the external light-electrical effect. But even years before Einstein had worked at the photoeffect and already made experiments on it. For that reason the article gives a short survey about the history of the lightelectric effects. Lenard's basical work about the release of the photoelectrons is dealt with in detail, without which Einstein would scarcely have found his lightquanta. Furthermore it is shown how difficult it was for the physicists to give up--at least partially--the traditional view of the undulation nature of light, and how they searched to explain the great energies of the photoelectrons. On the other side it is set forth how Einstein's formula of lightquanta was gradually confirmed. The tragical development of Einstein's personal relations with Johannes Stark and Philipp Lenard are briefly described. Stark was one of the few who supported Einstein's ideas at the beginning. Only with the Compton-effect, which could only be quantitatively interpreted by means of lightquanta and the special theory of relativity 1923, the way was free for the general acceptance of the lightquanta. Einstein did not agree to the obtained dualism of undulation and corpuscle; he had a different solution in mind about the fusion of the two forms of appearance of light. PMID- 17338402 TI - [Hermann Samuel Reimarus' theory of "modes of life" and "drives"]. AB - This essay focuses on Hermann Samuel Reimarus' (1694-1768) theory of "modes of life" and natural "drives" or "tendencies" (Triebe) in Allgemeine Betrachtungen uber die Triebe der Thiere, hauptsdchlich uber ihre Kunsttriebe (1760). Reimarus combines the notion of a systemic, organized inner order of organs, in which "functions" and corporeal dispositions correspond to each other, with a system of regulated "actions" of individual organic bodies. These "actions" rely on a "basic drive" (Grundtrieb) of "self-preservation", that Reimarus differentiates into "mechanic drives" (mechanische Triebe), "imagination drives" (Vorstellungstriebe) und "voluntary drives" (willkiirliche Triebe). Voluntary drives are again divided into "affection-drives" (Affectentriebe) and "art drives" (Kunsttriebe). Mechanic drives automatically initiate and sustain physiological processes of the system of organs, imagination drives establish transitions between sense perception, imagination, memory, and recognition, and art-drives regulate, as schemes or "m odels" which imply some degree of skill, "action" (Handlung)-based relations between individual organic bodies and their environments. Further on, humans possess a specific art-drive, based on "reason" (Vernunft), that is not naturally determined as a goal-directed "action": While the "modes of life" of animals are perfect in themselves in combining systems of drives and organic dispositions, humans are perfectible living beings with the faculty of "reflection". Plants are for Reimarus not living beings, because their existence relies only on "mechanical drives" without a central acting entity of perceptions. PMID- 17338403 TI - [Once again the so-called Testament of Hippocrates]. AB - This study is dealing with the so-called Testament of Hippocrates, a short ethic about the doctor's background, knowledge, character, appearance and behaviour towards the patient. Along with the three well-known Greek manuscripts the author is looking at two other by now unknown codices, so that the two Greek versions are accompanied by a third and larger version. After a careful consideration of the relations between the different versions he is discussing all readings of the codices explaining the terms within the background of the history of medicine. At the end he is presenting a reconstruction of the Greek original together with a German translation. PMID- 17338404 TI - [Scabies and the significance of "suriones" in the handwritten manuscripts of Hildegard von Bingen]. AB - In her studies on nature and medicine, the "Liber simplicis medicinae" (LSM or "Physica") and the "Liber compositae medicinae" (LCM or "Causae et Curae"), Hildegard von Bingen mentions Scabies (mange) in several passages. She characterizes "suren aut (= or) sneuelzen" as the cause of the disease, which she calls also "gracillimi vermiculi", that is, tiny worms that burrow into the human skin ("ubi suren aut sneuelzen hominem comedendo ledunt"). In this context the meanings of the German-ancestor terms "suren aut sneuelzen", which are found in the Latin text concerning the "Alia Mynza", are still disputed. The question whether Hildegard knew the cause of scabies the author discusses on the basis of ancient and medieval sources as well as modem medical historical and philological/linguistic research approaches. He concludes that Hildegard was able not only to describe the symptoms exactly, but also to define the cause of the disease as a special parasite. Consequently, she differentiates other diseases of the skin, such as "grint", from scabies. The proposed interpretation of "sneuelzen" as the tick is untenable. The assumption that both terms are synonyms for sarcoptes scabiei can be confirmed by philological and medical historical research. PMID- 17338405 TI - [Peter Plett and other discoverers of cowpox vaccination before Edward Jenner]. AB - Before Edward Jenner tested the possibility of using the cowpox vaccine as an immunisation for smallpox in humans in 1796, at least six people had done the same several years earlier. However, the findings of these six people regarding the cowpox vaccination are either hardly known or have even been forgotten. For the first time, the originally scattered information on the procedures used by these six people has been gathered and will be presented in this article. Detailed attention will be given to the works of the teacher Peter Plett (1766 1823), the only one to recognize the importance of his discovery for mankind. In 1790 and 1791/92, Plett reported his findings to the Medical Faculty of the University of Kiel. The faculty disregarded Plett's reports by neither responding to them nor changing their methods of immunisation, as the faculty at that time was still in favour of variolation. This article contains the available information and references concerning Plett's discovery, including the entire sources from 1802 and 1815 describing his findings. PMID- 17338406 TI - [Dating 'Curae Platearii']. PMID- 17338410 TI - [Living with sickle cell anemia. A painful disease]. PMID- 17338411 TI - [Physiopathology and treatment of sickle cell anemia]. PMID- 17338412 TI - [Sickle cell anemia, a history of four partners]. PMID- 17338413 TI - [Vaso-occlusive pain crises in children with sickle cell anemia]. PMID- 17338414 TI - [Care of children with sickle cell anemia in the health community]. PMID- 17338415 TI - [Feelings of loneliness and self pity in sickle cell anemia]. PMID- 17338416 TI - [Sickle cell anemia and social vulnerability, an accumulation of handicaps]. PMID- 17338417 TI - [Maternal-child health in Romania]. PMID- 17338418 TI - Will care checks raise standards? PMID- 17338419 TI - Does organ removal improve quality of life for a child with severe disabilities? PMID- 17338420 TI - Why you need to join the electronic revolution. PMID- 17338421 TI - How one nurse made a business of caring. PMID- 17338422 TI - Avian influenza and pandemics. AB - The confirmation of H5N1 avian influenza in England has caused renewed concern over the prospect of a global influenza pandemic. This article outlines the extent of government contingency plans for an influenza pandemic and the role healthcare workers will be expected to play. PMID- 17338423 TI - Skeletal system. Part Three--The axial skeleton. PMID- 17338424 TI - Use of tens in pain management. Part One: How TENS works. AB - Transcutaneous electrical nerve stimulation machines are widely available and used to treat many painful conditions. They are relatively inexpensive and, when used correctly, have few side-effects. This article, the first in a two-part series, looks at how this process works and the contraindications associated with it. PMID- 17338425 TI - PDGF-B gene single-nucleotide polymorphisms are not predictive for disease onset or progression of IgA nephropathy. AB - BACKGROUND: Few genetic factors have been identified that determine susceptibility to and progression of IgA-nephropathy (IgAN). Given that IgAN is usually characterized by mesangioproliferative glomerulonephritis and that PDGF-B is of central pathophysiological relevance in this process, we analyzed four single-nucleotide polymorphisms (SNPs) of the PDGF-B gene to evaluate a possible association of these SNPs with disease onset and progression, histological grading and responses to ACE inhibitor (ACEi) therapy. METHODS: The total study population consisted of 195 IgAN patients (127 from southern Italy and 68 from northern Germany) and 200 healthy controls (100 from each region). All four SNPs were in Hardy-Weinberg equilibrium and genotype distributions did not differ between patients and controls in either region. RESULTS: SNP distribution in Italian patients reaching end-stage renal disease (n=45) also was not significantly different from patients maintaining a serum creatinine below 1.2 mg/dl (n=60) during 5.6 +/- 5.5 years of follow-up. Furthermore, we failed to detect significant effects of any SNP on the slope of 1/serum creatinine, proteinuria level or the antiproteinuric response to ACEi. Additionally, particular PDGF-B genotypes did not correlate with histological grading using the Lee classification. CONCLUSION: We conclude that none of the four PDGF-B SNPs is related to the onset of IgAN in two different populations and that none of them has a major influence on the course of IgAN. PMID- 17338426 TI - Association between the clara cell secretory protein (CC16) G38A polymorphism and the progression of IgA nephropathy. AB - AIMS: Clara cell secretory protein (CC16) is a protein with anti-inflammatory and immunomodulatory properties. Moreover, both CC16 gene knockout and antisense transgenic mouse models developed glomerulonephritis resembling IgA nephropathy (IgAN). In the present study, we evaluated the influence of the G38A polymorphism in the CC16 gene exon 1 on the development and progression of IgAN. METHODS: Korean patients with biopsy-proven IgAN (n=267) with a minimal follow-up of 4 years (mean +/- SD 103.8 +/- 52.6 months) were recruited. Healthy normal subjects (n=315) were included as controls. The G38A polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: GG, GA and AA genotype frequencies were 36.3, 50.2 and 13.5% in IgAN patients, respectively, and 34.3, 50.2 and 15.5% in controls (chi2 = 0.596, p = 0.742). The G allele frequency was 0.614 in IgAN patients and 0.594 in controls (chi2 = 0.429, p = 0.512). Moreover, the GG genotype frequencies were 40.4% in patients showing stable disease course and 26.6% in those with progressive disease (chi2 = 4.029, p = 0.045). Patients with the GG genotype showed a better outcome by Kaplan-Meier analysis in terms of renal survival (p = 0.043). The CC16 polymorphism remained an independent risk factor for progression after multivariate analysis (Cox regression model, HR for CC16 AA genotype: 2.34, 95% CI 1.19-4.64, p = 0.014). CONCLUSION: Our results suggest that CC 16 gene G38A polymorphism is not associated with the development of IgAN, but that it is an important marker of progression in IgAN. PMID- 17338427 TI - Factors associated with anemia among incident pre-dialysis patients managed within a French care network. AB - BACKGROUND AND AIMS: Despite guidelines concerning the management of renal anemia, the international literature reports that a large proportion of pre dialysis patients have hemoglobin values lower than the recommended level. The present study analyzed the evolution of pre-dialysis Hb levels and erythropoietin use over a 4-year period and investigated factors associated with anemia. METHODS: A total of 1315 patients initiating dialysis in Lorraine, France, were enrolled since 2001-2004. For each year, anemia, defined by Hb <11 g/dl, and erythropoietin use were investigated in three groups: all patients, patients whose dialysis was planned and patients whose dialysis was unplanned. RESULTS: At initiation of dialysis, all groups showed increases over time in mean hemoglobin levels, proportion of patients without anemia and with erythropoietin therapy. Among patients whose first dialysis was planned in 2004, 43.8% had anemia and 67.9% had received erythropoietin, compared with 75.4% and 29.4%, respectively, when dialysis was unplanned. Patients receiving unplanned dialysis were more likely to have anemia (odds ratio (OR) = 2.6), as were those with a serum albumin level < 3.5 g/dl (OR = 2.1), body mass index < 30 kg/m2 (OR = 1.9) (all p < 0.001) or glomerular filtration rate < 10 ml/min/1.73 m2 (OR = 1.4, p = 0.04). The year of dialysis initiation was also associated with anemia (p = 0.024). CONCLUSION: The proportion ofpatients starting dialysis with anemia might be reduced by earlier nephrology referral leading to erythropoietin administration, planned first dialysis while residual renal function remains, and greater attention to nutritional status. PMID- 17338428 TI - Evaluation of the role of severe hyperparathyroidism on coronary artery calcification in dialysis patients. AB - BACKGROUND: Chronic kidney disease (CKD) patients are at a high risk of dying from a cardiovascular event, mainly due to coronary calcification. Among the various uremic and dialysis-specific risk factors for coronary calcification are mineral metabolism disorders. The role that secondary hyperparathyroidism (SHPT) consequent to the altered calcium and phosphate metabolism plays in the pathogenesis of coronary calcification remains unclear. The aim of this study was to evaluate the prevalence of coronary artery calcification in dialysis patients with severe SHPT submitted to multislice coronary tomography (MSCT) and to identify risk factors for coronary calcification. METHODS: This study involved 23 adult dialysis patients (age >18 years) with severe SHPT who were candidates for parathyroidectomy (PTX). All were submitted to MSCT and bone densitometry during the month preceding PTX. Fasting blood samples were collected immediately before surgery. Markers of mineral metabolism, including ionized calcium, phosphorus, alkaline phosphatase, intact-parathyroid hormone (iPTH), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand, were analyzed. Dyslipidemia was assessed by determination of LDL, HDL and VLDL-cholesterol and triglyceride levels. Agatston units (AU) were used to calculate calcium scores. RESULTS: No coronary calcification was found in 30% of the patients. Moderate (calcium score > 100 AU) and severe (calcium score >400 AU) calcification was observed in 12 and 36% of the patients, respectively. In the univariate analysis, calcium volume correlated positively with VLDL-cholesterol (r = 0.44; p = 0.03) and, albeit less than significantly, with age (r = 0.35; p = 0.09), triglycerides (r = 0.39; p = 0.05) and Framingham risk index (r = 0.37; p = 0.07). We also found that OPG correlated negatively with bone mineral density at the L2-L4 lumbar vertebrae (r = -0.54; p = 0.007) and femoral neck (r = -0.43; p = 0.04). CONCLUSIONS: Although high levels of PTH should be considered a risk factor for cardiovascular death, the real role of severe SHPT on coronary calcification is to be clarified. PMID- 17338429 TI - Algorithm for optimal dialysis access timing. AB - BACKGROUND: Acute initiation of dialysis is associated with increased morbidity due to access and uremia complications. It is frequent despite early referral and regular out-patient control. We studied factors associated with end-stage renal disease (ESRD) progression in order to optimize the timing of dialysis access (DA). METHODS: In a retrospective longitudinal study (Study 1), the biochemical and clinical course of 255 dialysis and 64 predialysis patients was registered to determine factors associated with dialysis-free survival (DFS). On the basis of these results an algorithm was developed to predict timely DA, defined as >6 weeks and <26 weeks before dialysis initiation, with too late placement weighted twice as harmful as too early. The algorithm was validated in a prospective study (Study 2) of 150 dialysis and 28 predialysis patients. RESULTS: Acute dialysis was associated with increased 90-day hospitalization (17.9 vs. 9.0 days) and mortality (14% vs. 6%). P-creatinine and p-urea were poor indicators of DFS. At any level of p-creatinine, DFS was shorter with lower creatinine clearance and vice versa. Patients with systemic renal disease had a significantly shorter DFS than primary renal disease, due to faster GFR loss and earlier dialysis initiation. Short DFS was seen with hypoalbuminemia and cachexia; these patients were recommended early DA. The following algorithm was used to time DA (units: 1iM and ml/min/1.73 m2): P-Creatinine - 50 x GFR + (100 if Systemic Renal Disease) >200. Use of the algorithm was associated with earlier dialysis placement and a fall in acute dialysis requirements from 50% to 23%. The incidence of too early DA was unchanged (7% vs. 9%), and was due to algorithm non application. The algorithm failed to predict imminent dialysis in 10% of cases, primarily due to acute exacerbation of stable uremia. Dialysis initiation was advanced by approximately one month. CONCLUSIONS: A predialysis program based on early dialysis planning and GFR-based DA timing may reduce the requirement for acute dialysis initiation and patient morbidity and mortality, at the cost of slightly earlier dialysis initiation. PMID- 17338430 TI - Acute interstitial nephritis after cocaine sniffing. AB - We report the case of a 42-year-old man who developed biopsy-confirmed acute interstitial nephritis (AIN) after cocaine sniffing. He required a few hemodialysis sessions but fully recovered within 3 weeks after cocaine withdrawal and a short course of corticosteroids. AIN should be recognized as a potential cause of acute renal failure in cocaine users, and a history of cocaine use should be carefully elicited in patients with unexplained AIN. PMID- 17338431 TI - Focal segmental glomerulosclerosis in association with Cushing's disease. AB - Focal segmental glomerulosclerosis (FSGS) may be idiopathic or secondary to a variety of causes. Clinical distinction between primary and secondary forms of FSGS has crucial therapeutic consequences. Whereas the former may respond to immunosuppressive therapy, treatment of secondary forms of FSGS must aim to resolve the underlying diseases. Although the combination of nephrotic syndrome and Cushing's syndrome has been described anecdotally, the causal relationship between these two diseases remains controversial. We report herein a 37-year-old man who presented with lower extremity pitting edema. Heavy proteinuria and mild renal insufficiency prompted to perform a kidney biopsy and the specimen showed FSGS. On the other hand, admission physical examination was notable for a Cushingoid appearance. After endocrinological investigations, the patient was diagnosed as having Cushing's disease caused by pituitary adrenocorticotropic hormone-producing microadenoma. Immunosuppressive therapy for the treatment of FSGS was not carried out and we treated his Cushing's disease with transsphenoidal resection of the pituitary microadenoma. Surprisingly, resolution of heavy proteinuria occurred when the patient's physical features characteristic of Cushing's disease were gradually resolved 3 months later. This case suggests a possible association of Cushing's disease with FSGS. PMID- 17338432 TI - Thrombotic microangiopathy in a sirolimus-treated renal transplant patient receiving gemcitabine for lung cancer. AB - BACKGROUND: Many etiologies lead to thrombotic microangiopathy (TMA), amongst which are antineoplastic chemotherapies. Gemcitabine, a nucleoside analogue, has been approved for the treatment ofbladder and advanced non-small cell lung carcinomas (NSCLC). The reported incidence of gemcitabine-associated TMA in the literature is low, ranging from 0.015-0.31%. METHODS: Herein, we describe the first reported case of gemcitabine-induced TMA in a renal transplant patient. This occurred in a 54-year-old male transplant recipient undergoing sirolimus based immunosuppression. In February 2005, he was diagnosed to have NSCLC, for which he received dual chemotherapy, including carboplatin and gemcitabine. After the third cycle he developed TMA. RESULTS: On admission, he presented with weakness, edema, normal blood pressure, leucopenia (2440/mm3), thrombopenia (11,000/mm3), hemolytic anemia with hemoglobin at 8 g/dl, schistocytes between 18 33% per hundred, increase in lactate dehydrogenase at 600 IU/l (N <380), and decreased haptoglobin at 0.29 g/l. Renal function was stable: serum creatinine was 1.3 mg/dl, albuminemia 30 g/l, proteinuria was present at 3 g/l in association with microscopic hematuria, and sirolimus trough level was 6.4 ng/ml. Treatment included infusions of fresh frozen plasma, withdrawal of sirolimus, which was replaced by mycophenolate mofetil, and suspension of chemotherapy. He fully recovered from TMA within 4 weeks. The concomitant use of sirolimus, which inhibits vascular endothelial growth factor, plus gemcitabine may have resulted in TMA. PMID- 17338433 TI - Gastric calciphylaxis in a patient with a functioning renal allograft. AB - Calciphylaxis or calcific uremic arteriolopathy (CUA), not uncommon in the dialysis population, has also been reported in renal transplant recipients with varying stages of renal dysfunction. While cutaneous involvement in both populations is the most common feature, visceral involvement is rarely described. We report a patient with a long-standing functioning renal allograft who presented with visceral calciphylaxis in a Dieulafoy lesion requiring gastrectomy. Histopathology revealed typical features of CUA. The current literature describing CUA in post-transplant patients is reviewed. PMID- 17338434 TI - Liquefaction necrosis of mitral annulus calcification in a patient with chronic renal failure: an unrecognized diagnosis. AB - Mitral annulus calcification is one of the most common cardiac calcifications. In patients with end-stage renal disease undergoing echocardiography, it can be detected in more than 40%. A specific form of mitral annulus calcification is liquefaction necrosis. It is often not adequately recognized by echocardiographers or clinicians and can be mistaken for cardiac tumor or infective vegetation. Here we report a case of liquefaction necrosis of mitral annulus calcification, mimicking an infective vegetation of the mitral valve apparatus in a patient with chronic renal failure. PMID- 17338435 TI - Increased eosinophilia after transfer of a patient to peritoneal dialysis for resolution of a hemodialysis-associated hypersensitivity reaction. PMID- 17338436 TI - Recent insights into microbial physiology. PMID- 17338437 TI - DNA supercoiling and bacterial gene expression. AB - DNA in bacterial cells is maintained in a negatively supercoiled state. This contributes to the organization of the bacterial nucleoid and also influences the global gene expression pattern in the cell through modulatory effects on transcription. Supercoiling arises as a result of changes to the linking number of the relaxed double-stranded DNA molecule and is set and reset by the action of DNA topoisomerases. This process is subject to a multitude of influences that are usually summarized as environmental stress. Responsiveness of linking number change to stress offers the promise of a mechanism for the wholesale adjustment of the transcription programme of the cell as the bacterium experiences different environments. Recent data from DNA microarray experiments support this proposition. The emerging picture is one of DNA supercoiling acting at or near the apex of a regulatory hierarchy where it collaborates with nucleoid-associated proteins and transcription factors to determine the gene expression profile of the cell. PMID- 17338438 TI - Variations on a theme: diverse N-acyl homoserine lactone-mediated quorum sensing mechanisms in gram-negative bacteria. AB - Many Gram-negative bacteria employ a mechanism of cell-cell communication known as quorum sensing (QS). The role of QS is to enable the cells in a culture to coordinate their gene expression profile with changes in the population cell density. The best characterized mechanisms of QS employ N-acylated homoserine lactones (AHLs) as signalling molecules. These AHLs are made by enzymes known as LuxI homologs, and accumulate in the culture supernatant at a rate proportional to the increase in cell density. Once the AHL concentration exceeds a certain threshold value, these ligands bind to intracellular receptors known as LuxR homologs. The latter are transcriptional regulators, whose activity alters upon binding the AHL ligand, thereby eliciting a change in gene transcription. Over the last five years, it has become increasingly obvious that this is a rather simplistic view of AHL-dependent QS, and that in fact, there is considerable diversity in the way in which LuxI-R homologs operate. The aim of the current review is to describe these variations on the basic theme, and to show how functional genomics is revolutionizing our understanding of QS-controlled regulons. PMID- 17338439 TI - The role of two-component regulation systems in the physiology of the bacterial cell. AB - Two-component regulation systems (TCRSs) are the dominant type of signal transduction system in prokaryotes that are used to inform the cellular trancriptional machinery (and additional targets for regulation, like the motility apparatus) about actual changes in the extracellular physicochemical conditions. We now review their molecular structure and enzymatic characteristics, their mutual interactions and its implications, and their role in cellular physiology. Specific emphasis is placed on the ArcB/A system, a representative of the phosphorelay type of TCRS, and a key player in the adjustment of the cellular make-up of enterobacteria in response to alterations in the oxygen availability. Also some applied aspects of the TCRSs are discussed, i.e. their role as a target to develop new anti-bacterials and their application in biotechnology (or: 'synthetic biology'). PMID- 17338440 TI - Deciphering a complex genetic regulatory network: the Bacillus subtilis sigmaW protein and intrinsic resistance to antimicrobial compounds. AB - Bacillus subtilis, a spore-forming soil bacterium, is the preeminent model system for the analysis of gene regulation in Gram-positive bacteria. Early genetic analyses established that this organism uses alternative sigma (sigma) subunits to reprogram RNA polymerase to activate genes required for growth phase transitions, motility, general stress response, and sporulation. Unexpectedly, the genome sequence predicts the presence of an additional seven a subunits: all members of the extracytoplasmic function (ECF) a subfamily of regulators that typically respond to cell envelope stresses. Here, we review our current understanding of one of these a factors, sigmaW, with an emphasis on experimental strategies and approaches. Exposure to cell envelope active antibiotics and toxic peptides triggers a signaling cascade that releases sigmaW from its cognate anti sigma thereby allowing transcription of approximately 60 sigmaW-dependent genes. These genes encode proteins that inactivate, sequester, or eliminate toxic compounds from the cell. PMID- 17338441 TI - Editorial: mental health and intellectual disability. PMID- 17338442 TI - Mental health services for people with intellectual disability in Israel--a review of options. AB - Intellectual disability (ID) (often also referred to as "mental retardation," "development disability," "mental handicap," "learning disability" or as "generalized learning difficulties") is common in all countries. Many people with ID suffer from psychiatric/behavioral/emotional disturbances (known as "dual diagnosis"). Specialist psychiatric services are needed to address these problems effectively, but are not currently available in most countries, including Israel. This article sets out to describe the problems, current services in Israel, approaches in other countries and proposed solutions for Israel. We believe it important to enforce laws against discrimination based on disability, to raise the general awareness, knowledge and skills among generic mental health professionals on the topic of intellectual disability by inclusion in university, postgraduate and in-service training curricula, to work towards a form of subspecialty within psychiatry along the lines of the model in the United Kingdom and to establish specialized psychiatric services, possibly functioning as back up to the generic psychiatric services. PMID- 17338443 TI - Assessment of mental health problems in people with intellectual disabilities. AB - Although it is widely accepted that individuals with intellectul disabilities face an increased vulnerability to developing mental health problems, there is currently a lack of agreement about the most appropriate form of assessment. When applied to people with intellectual disabilities, there is no consensus about which problems should be included in the term "mental health problem," and identifying mental illness is far from straightforward. The adoption of standardized classification systems assumes that individuals with intellectual disabilities have adequate linguistic skills and they present mental health problems in the same way as members of the general population. Yet, individuals with intellectual disabilities are less likely to fulfill verbal expectations that are the basis of current classification systems and many exhibit problem behaviors incompatible with existing criteria. Nevertheless, accurate diagnosis provides a clear direction for interventions. Although there is currently a lack of consensus about which instruments are most effective, the routine use of valid and reliable assessment and monitoring tools may significantly improve the quality of research and care. The complexity of factors influencing the mental health of individuals with intellectual disabilities has implications for how these needs can be effectively met. Clearly, diagnostic classification provides only partial guidance to morbidity and the quality of life experienced and mental health services increasingly adopt a problem-based, "biopsychosocial" approach to assessment and treatment delivered by multidisciplinary teams. The most basic and vital role of carers within this context is the awareness that a person with intellectual disabilities may suffer from a mental illness. Carers play a central role in recognising possible mental illness, making referrals for further psychiatric assessment and providing diagnostic information and treatment feedback. In the absence of information about the manifestation of mental health problems in individuals with intellectual disabilities, it is likely that the signs of mental illness will be overlooked. Training initiatives, aimed at increasing the ability of care staff to recognise the signs of mental illness and to make informed referral decisions, are vital in ensuring adequate access to mental health services by individuals with intellectual disabilities. PMID- 17338444 TI - A 10-year review of a Hong Kong model for mental health care of people with intellectual disability. AB - Following the movement from institutionalization to community care, there has been a transformation of services for people with intellectual disability over the past few decades. Kwai Chung Hospital in Hong Kong is a pioneer in Asia that took the initiative of improving the mental health care for this underserved population by setting up a specialist unit called the Psychiatric Unit for Learning Difficulties (PULD) 10 years ago. This new service was established through re-engineering of existing resources and re-distribution of manpower within the psychiatric hospital. This paper reviews the work of PULD and examines its achievements. By sharing the experiences of PULD, it is hoped that health providers currently without such a specialist service can make similar reforms to enhance their provisions for people with intellectual disability and mental health problems. PMID- 17338445 TI - A review of suicidality in persons with intellectual disability. AB - It has been assumed that impaired intellectual capacity could act as a buffer to suicidality in the population of persons with intellectual disability (ID), developmental disability or mental retardation. The few studies conducted contest this assumption and in fact findings show that the characteristics of suicidality in that population were very similar to that in persons without intellectual disability. This paper reviews the studies conducted and describes the symptomatology in this population, risk factors, screening and intervention. Professionals working with this population should therefore be aware of and assess for this behavior, since in one study it was found that many caregivers were unaware of suicidality in their clients. Only two studies had systematically examined differences between suicidal and non-suicidal individuals with ID with regard to risk factors. Risk factors found were history of prior psychiatric hospitalization, comorbid physical disabilities, loneliness, sadness, depression or anxiety. There is limited research on intervention for suicidal behavior in the ID population, but professionals should consider risk factors for suicide in this population and intervene when suicidal risk/behavior is found. PMID- 17338446 TI - Psychopharmacology and applied behavioral analysis: tandem treatment of severe problem behaviors in intellectual disability and a case series. AB - Many individuals with intellectual disability will at some time in their lives engage in problem behaviors that may place them and others at risk, and reduce their opportunities for healthy psychosocial functioning. These behaviors may reach severe proportions in both intensity and frequency, necessitating intervention. Both psychiatrists and behaviorists are often approached regarding negative behaviors in intellectual disability, and each discipline offers key tools in behavioral assessment and resolution. We believe that the coordinated effort of these two disciplines affords the most comprehensive and efficacious method of assessing, understanding and treating a wide range of problem behaviors and associated psychiatric pathology in individuals with various forms of intellectual disability. This paper briefly reviews the background of problem behaviors in intellectual disability and treatment of such disturbances through separate psychiatric and applied behavioral modalities, followed by the proposed coordinated neurobehavioral model. A case series ensues, describing the successful application of the neurobehavioral model to the severe problem behaviors demonstrated by three individuals with intellectual disability related to autism, Cornelia de Lange syndrome and traumatic brain injury. PMID- 17338447 TI - Mental health for persons with intellectual disability in the post deinstitutionalization era: experiences from British Columbia. AB - The delivery of mental health services to persons with Intellectual Disability (ID) in British Columbia (BC), Canada, is worth documenting because BC is one of the few jurisdictions in the world to completely close its institutions for people with ID. This paper documents the delivery of mental health care in BC for this population and contrasts the dream versus the reality of community living for people with dual diagnosis (mental illness coupled with an intellectual disability). PMID- 17338448 TI - Trends in mental health services for people with intellectual disability in residential care in Israel 1998-2004. AB - Persons with intellectual disability (ID) have more mental health problems than the general population and utilize psychiatric service to a greater extent. This study was conducted to look at trends over time in the number of psychiatrists recruited, psychiatric medication and hospitalization for persons with ID in residential care in Israel. Data was extracted for the 1998-2004 period from the annual surveys conducted of medical service in all residential care centers in Israel by the Office of the Medical Director. Results showed an increase in psychiatrists working with this population, from 1.08 psychiatrist per 1,000 study population in 1998 to 2.23 in 2004, psychotropic medication also increased from 45% to 52% over the same period, but psychiatric inpatient hospitalization decreased from 5.48 to 4.99 per 1,000 study population. It is concluded that there has been an improvement in psychiatric service to this residential care population over the study period, but there is a need for a formal subspecialty in psychiatry, training and research. PMID- 17338449 TI - An alternative model for psychiatric service delivery for people with intellectual disabilities in a vocational rehabilitation center. AB - The prevalence of mental illness in the intellectually disabled (ID) population is high. Because of their special characteristics, such as involvement of multiple carers (family, social services, protected housing staff, vocational instructors), linguistic limitations and the need for a familiar and steady environment, these patients require special therapeutic consideration. In Israel, as in many other countries, people with ID (PWID) receive psychiatric services from general psychiatric outpatient clinics and hospitals; their treatment is generally not specifically tailored to their needs, and hence often suboptimal. In this article we will review some models of psychiatric service delivery for PWID and present an alternative model that we have developed. Our service has been operating since December 1998; it is based upon cooperation between the municipal social services and the local psychiatric outpatient clinic, and is provided in a vocational rehabilitation center where most mild to moderate ID individuals in our area, the city of Bat Yam, are employed. During the first five years (1999-2004) of the operation of the service, 42 people (about half the total number of clients passing through the vocational rehabilitation center during this period) were examined by the psychiatrist; 37 of them (88%) had at least one psychiatric diagnosis. There were especially high rates of adjustment disorder (26% of all principal diagnoses) and of behavior disorder (24% of all principal diagnoses). This model for psychiatric service delivery for PWID in a vocational-rehabilitation center, based as it is on cooperation between the different care agencies, facilitates more accurate psychiatric diagnosis and hence the provision of more appropriate treatment, which in practice usually consists of a combination of pharmacological and behavioral treatment together with educational programs and support for families and staff. Based on our positive experience with this model, we believe that it is the most suitable framework of treatment for adults with dual diagnosis, and that it should be adopted in other areas. PMID- 17338450 TI - Psychiatric manifestations in Turner Syndrome: a brief survey. AB - Turner Syndrome (TS) is a relatively common genetic syndrome in which a woman has a 45XO or 45XO/46XX mosaic karyotype. Although it is not associated with any psychiatric syndrome, several case reports in the literature describe a similar constellation of symptoms in TS that may represent a biologically-based entity. This article reviews existing case reports and seeks common characteristics among them, which may include mild psychosis with stress-precipitated onset, prominent mood features, and some features that may resemble organic disease. PMID- 17338451 TI - Measuring unawareness of deficits among patients with traumatic brain injury: reliability and validity of the Patient Competency Rating Scale--Hebrew version. AB - BACKGROUND: Unawareness of deficits is a frequent symptom of traumatic brain injury (TBI), affecting motivation and compliance with treatment. The goal of this study was to validate a Hebrew version of the most commonly used measure of post-TBI unawareness of deficits: the Patient Competency Rating Scale (PCRS). METHOD: Seven groups of participants were studied: Patients with TBI (two groups), their family members, their therapists (two groups), and matched controls and their family members. The PCRS scores of patients, relatives and therapists were analyzed. RESULTS: The adapted scale shows adequate inter-item consistency coefficients, similar to those reported with the original version, and high inter-rater reliability. As expected, the scale significantly differentiates between patients and controls, shows high positive correlations with depression and is composed of the four expected awareness factors. Normative data are also presented. LIMITATIONS: The number of participants in each of the seven study groups and the specificity of the stage at which the patients were examined may limit the generalization power of our findings. CONCLUSIONS: The Hebrew version of the PCRS is a reliable and valid scale for measuring post-TBI deficits in self-awareness and may be used for clinical and research purposes. PMID- 17338452 TI - Finger habits: their effects and their treatments--part 1. PMID- 17338453 TI - Defining duties in the business arena. "When the front desk hums, the back office sings". PMID- 17338454 TI - It's happening again...change! PMID- 17338455 TI - Service animals: access to dental facilities. PMID- 17338456 TI - The smoke never clears. PMID- 17338458 TI - Insurance: it's all about choice. PMID- 17338457 TI - Early retirement sounds good--but is it? PMID- 17338459 TI - Management of asymptomatic wisdom teeth. PMID- 17338460 TI - What every dentist should know about malignant hyperthermia. PMID- 17338461 TI - Dental observations: 2006. PMID- 17338462 TI - A clinico-pathologic correlation. AB - Bisphosphonates (BPs) have been in clinical use for performing bone imaging, treating different metabolic bone diseases, and managing osteolysis and the hypercalcemia associated with some cancers since the late 1960s. Although these agents are extremely effective at treating these conditions, recent publications have noted a possible sequela of treatment with BPs is bisphosphonate-related osteonecrosis (BRON) of the jaws. In the past few years, a great deal of attention has been paid to recognition and management of different issues surrounding patients being treated with bisphosphonates by many health care providers, including dentists and dental specialists. This article will review some of the basic principles behind bisphosphonate therapy and its side effects, and summarize the management guidelines used in BP therapy. We will also report one of the 11 cases that we have identified and managed in our clinic in the past five years. PMID- 17338463 TI - A clinico-pathologic correlation. PMID- 17338464 TI - Mandibular ceramic laminate veneer. PMID- 17338465 TI - Geographic stomatitis. PMID- 17338466 TI - Pirate teeth. PMID- 17338467 TI - Follow-up on the Combat Methamphetamine Epidemic Act of 2005: review of oral decongestants. PMID- 17338468 TI - Prescribing and dispensing errors: a call to action for pharmacists. PMID- 17338469 TI - Plan B: a long-sought opportunity. PMID- 17338470 TI - Demonstrating pharmacists' value: this is the time and tide to work together. PMID- 17338471 TI - 'Bringing your medicines to life': APhA building new annex to headquarters. PMID- 17338472 TI - Recall of A1C, blood pressure, and cholesterol levels among community pharmacy patients with diabetes. AB - OBJECTIVES: To determine the proportion of patients with diabetes mellitus who knew their personal and target glycosylated hemoglobin (AIC), blood pressure, and low density lipoprotein cholesterol (LDL-C) (ABC) levels and the proportion of patients whose recalled ABC levels were below targets set by the American Diabetes Association (ADA). DESIGN: Cross-sectional survey. SETTING: 35 community and clinic pharmacies in May 2003 through May 2004. PARTICIPANTS: 132 student pharmacists in Ambulatory Pharmaceutical Care Clerkship who recruited a convenience sample of 816 evaluable patients with diabetes. INTERVENTION: Student administered questionnaires. MAIN OUTCOME MEASURES: Patients' self-reported and target ABC values and comparison of these with recommended ADA guidelines. RESULTS: The greatest number of patients were able to recall their personal blood pressure level (68%), followed by A1C (53%) and LDL-C (23%). Of those who knew their levels, one-half or fewer were within ADA targets for one or more ABCs. Only 1% of patients who were able to provide ABC levels were below all three ADA target values. Patients were most likely to provide an A1C target (43%), followed by blood pressure (35%) and LDL-C (21%). CONCLUSIONS: While almost three-quarters of the patients identified in community pharmacies knew their blood pressure levels, one-half or fewer knew their A1C or LDL-C levels. Fewer than 50% of patients reported even one ABC target number. Pharmacists should take advantage of this educational opportunity by working with patients with diabetes to increase their knowledge of these ABCs. PMID- 17338473 TI - Knowledge of appropriate acetaminophen doses and potential toxicities in an adult clinic population. AB - OBJECTIVE: To evaluate the knowledge of appropriate doses and potential toxicities of acetaminophen and assess the ability to recognize products containing acetaminophen in an adult outpatient setting. DESIGN: Cross-sectional, prospective study. SETTING: University adult general internal medicine (AGIM) clinic. PATIENTS: 104 adult patients presenting to the clinic over consecutive weekdays in December 2003. INTERVENTIONS: Three-page, written questionnaire. MAIN OUTCOME MEASURES: Ability of patients to identify maximum daily doses and potential toxicities of acetaminophen and recognize products that contain acetaminophen. RESULTS: A large percentage of participants (68.3%) reported pain on a daily or weekly basis, and 78.9% reported use of acetaminophen in the past 6 months. Only 2 patients correctly identified the maximum daily dose of regular acetaminophen, and just 3 correctly identified the maximum dose of extra-strength acetaminophen. Furthermore, 28 patients were unsure of the maximum dose of either product. Approximately 63% of participants either had not received or were unsure whether information on the possible danger of high doses of acetaminophen had been previously provided to them. When asked to identify potential problems associated with high doses of acetaminophen, 43.3% of patients noted the liver would be affected. The majority of the patients (71.2%) recognized Tylenol as containing acetaminophen, but fewer than 15% correctly identified Vicodin, Darvocet, Tylox, Percocet, and Lorcet as containing acetaminophen. CONCLUSION: Although nearly 80% of this AGIM population reported recent acetaminophen use, their knowledge of the maximum daily acetaminophen doses and potential toxicities associated with higher doses was poor and appeared to be independent of education level, age, and race. This indicates a need for educational efforts to all patients receiving acetaminophen-containing products, especially since the ability to recognize multi-ingredient products containing acetaminophen was likewise poor. PMID- 17338474 TI - Drug interaction between oral contraceptives and St. John's Wort: appropriateness of advice received from community pharmacists and health food store clerks. AB - OBJECTIVE: To estimate the extent to which community pharmacists and health food store clerks provide appropriate advice regarding a drug interaction between oral contraceptives and St. John's wort (SJW). DESIGN: Cross-sectional study. SETTING: Three community pharmacy chains and three health food store chains in four highly populated counties in California. PARTICIPANTS: Community pharmacists (n=99) and health food store clerks (n=84). INTERVENTION: Investigators, posing as consumers, telephoned pharmacists and health food store clerks and asked the following question: "Is there a problem with taking SJW with birth control pills?" MAIN OUTCOME MEASURES: Respondents were classified based on their ability to correctly identify the drug interaction (yes or no) and on the overall appropriateness (i.e., the absence of incorrect advice) of their advice. Comparisons were made between men and women respondents and between pharmacists and health food store clerks. RESULTS: Community pharmacists were more likely than health food store clerks to correctly identify the drug interaction (50.5% versus 10.9%; Xchi(1 df) = 54.32, P < 0.001). Overall, 31.8% of respondents provided inappropriate advice that implied the absence of a drug interaction (26.3% of 99 pharmacists and 34.8% of 184 health food store clerks; Xchi(1 df) = 2.15, P = 0.14). Appropriateness of advice varied significantly among the three pharmacy chains (P < 0.001) and the three health food store chains (P < 0.05). Responses did not differ by gender of respondents (P = 0.18). CONCLUSION: Lack of awareness of the potentially serious drug interaction between SJW and oral contraceptives by those who sell these products places the public at risk. Training and education, more comprehensive product labeling, and policies to refer consumers to drug information centers are needed. PMID- 17338475 TI - Texas community pharmacists' willingness to participate in pharmacist-initiated emergency contraception. AB - OBJECTIVES: To determine Texas community pharmacists' knowledge about and experience with emergency contraception (EC), their perceptions about and willingness to participate in pharmacist-initiated emergency contraception (PIEC), and whether their willingness is influenced by their background characteristics or experience with EC. DESIGN: Cross-sectional study. SETTING: Texas in November through December 2004. PARTICIPANTS: 300 community pharmacists. INTERVENTIONS: Mailed questionnaire consisting of 40 questions divided into three SECTIONS: experience with EC, perceptions about PIEC, and background information. MAIN OUTCOME MEASURES: Pharmacists' perceptions and behaviors regarding EC and PIEC, and their willingness to participate in PIEC. Bivariate analysis to assess background characteristics and experience with EC in relation to willingness to participate in PIEC; multiple regression to identify predictors of willingness to participate in PIEC. RESULTS: With a usable response rate of 51%, results indicate that most pharmacists (91.2%) had heard of EC, while 45.2% kept EC in stock. More than one half (57.8%) had dispensed EC, and 95.5% were aware that EC is most effective when taken within 72 hours. Some 27.4% were opposed to dispensing EC, primarily because of religious (86.1%) and moral (80.6%) beliefs. Most (57.7%) believed that there should be a minimum age (mean +/- SD, 17.25 +/- 1.93 years) for patients receiving EC. Less than one half (46.7%) had heard of PIEC. Although pharmacists agreed (3.42 +/- 1.38) that PIEC would enhance the role of community pharmacists, they were unwilling (2.71 +/- 1.54) to participate in PIEC. Significant predictors of willingness to participate in PIEC included background characteristics, experience with EC, as well as benefits and barriers associated with PIEC. A regression analysis indicated that these significant predictors accounted for 58.6% of the total variance in willingness to participate in PIEC. CONCLUSION: A majority of Texas community pharmacists were quite knowledgeable about and aware of EC, but fewer had actually dispensed EC. Most had not heard of PIEC before study participation, and their perceptions relating to PIEC were generally unfavorable. Potential barriers to PIEC outnumbered potential benefits for most pharmacists. Findings indicate that Texas community pharmacists were not willing to become involved in PIEC at the time of this study. PMID- 17338476 TI - Structural model of certified pharmacy technicians' job satisfaction. AB - OBJECTIVE: To determine the effects of worklife attitudes on certified pharmacy technicians' job satisfaction. DESIGN: Cross-sectional descriptive design. SETTING: United States in January 2004. PARTICIPANTS: Random sample of 3200 certified pharmacy technicians (CPhTs) acquired from the Pharmacy Technician Certification Board. INTERVENTION: Mail survey. MAIN OUTCOME MEASURES: Responses to previously validated instruments measuring quality of worklife attitudes. Hypothesized relationships between these worklife attitudes (job stress, future uncertainty, career commitment, organizational commitment, supervisor support, coworker support, employer support) and job satisfaction were tested with structural equation modeling. RESULTS: The results provided adequate support for the hypothesized, partially mediated (comparative fit index [CFI] = 0.091, root mean square error of approximation [RMSEA] = 0.073), fully mediated (CFI = 0.091, RMSEA = 0.073) and direct effects (CFI = 0.922, RMSEA = 0.066) models, each exhibiting moderate fit. As predicted, job stress negatively affected job satisfaction among CPhTs. However, the negative effects of job stress were mitigated by supervisor support, which, along with employer and coworker support, was positively related to job satisfaction. Future uncertainty also was found to be negatively related to job satisfaction; this relationship was mediated by organizational commitment. CONCLUSION: Job stress was present in CPhTs, although not to the degree pharmacists have reported it. Job stress negatively affected job satisfaction, but this was mitigated by supervisor support. CPhTs reported uncertainty about their future career plans. Commitment to their current employer lessened this uncertainty. Pharmacy managers should consider including CPhTs in goal setting and career planning. PMID- 17338477 TI - Effect of labor action on extent of and interest in unionization among Illinois staff pharmacists. PMID- 17338478 TI - Cost analysis of schizophrenia treatment with second-generation antipsychotic medications in North Carolina's Medicaid program. PMID- 17338480 TI - University and college of pharmacy collaboration to control health plan prescription drug costs. AB - OBJECTIVE: To describe the Raising Energy and Awareness in Campus Health (REACH) program, an innovative pharmacy practice model implemented within a self-insured employer. SETTING: University of Kentucky, Lexington. PRACTICE DESCRIPTION: A self-funded university-based health plan. PRACTICE INNOVATION/INTERVENTIONS: As part of a university-wide effort to control rising health care costs for 24,000 employees and dependents, four novel pharmacist services encompassed in the REACH program were provided: Co-Pay Counseling; Good Medicines; OutREACH; and Disease Management and Health Promotion. MAIN OUTCOME MEASURES: University health plan expenditures and health plan member out-of-pocket expenses for prescription medications. RESULTS: The REACH services were provided by 3.5 full-time equivalent pharmacists. Pharmacists evaluated health plan members' medications and conditions in an effort to identify more cost-effective treatment regimens in the Co-Pay Counseling program; provided confidential medication regimen review in the Good Medicines effort; provided informational programs at worksites within the university in the Out-REACH service; and worked with plan members and their health providers to prevent and/or minimize the impact of diseases such as diabetes and dyslipidemias. The overall university program and medication coinsurance strategy saved an estimated 1.6 million dollars in 2003-04. CONCLUSION: This unique package of employee benefits and services enabled the University of Kentucky to slow the growth of health care expenditures. Pharmacists were an important element in this effort. PMID- 17338479 TI - Effect of a personal automated dose-dispensing system on adherence: a case series. AB - OBJECTIVE: To evaluate the effect of the MD.2 Personal Medication System (MD.2) on patient medication adherence and refill persistence. DESIGN: Open noncontrolled case series. SETTING: Community pharmacy. PATIENTS: Three patients with a documented history of poor medication adherence and persistence. INTERVENTION: MD.2 placed in patients' homes for 3 months. MAIN OUTCOME MEASURES: Medication adherence (doses taken at prescribed times) and persistence (refills obtained at correct times) assessed before and after installation of MD.2. RESULTS: Installation of MD.2 resulted in medication adherence rates of greater than 99% in all three patients. Refill persistence rates improved in both patients who needed refills during the study period. Missed doses and other problems were mostly due to caregiver error in filling or programming MD.2. CONCLUSION: The MD.2 Personal Medication System had a positive effect on medication adherence and persistence in these three patients. Training and selection of caregivers may be especially important for effective use of the machine. Larger studies will be needed to validate these results. PMID- 17338481 TI - Henry Parr Hynson (1855-1921): community pharmacist advocate. PMID- 17338482 TI - Expanding childhood influenza immunization recommendations. PMID- 17338483 TI - New drugs: sitagliptin phosphate, telbivudine, and panitumumab. PMID- 17338484 TI - OTC device: temporal scanner TAT-2000C. PMID- 17338485 TI - A streetcar named more than desire: cultural competence revisited. PMID- 17338486 TI - Faith-based leaders' opinions before and after a youth tobacco prevention workshop. AB - To determine if religious leaders' (N = 253) opinions changed after a 1-day workshop on integrating a "Students Working Against Tobacco" educational program into Sunday school or other youth programs at church, participants, most of whom were African-American, completed a pretest and posttest survey. Leaders' opinions regarding their expertise in this area reflected more confidence following the workshop. Both before and after the workshop, they were firm in their belief that tobacco prevention programs have an impact and that tobacco use could be prevented. Surprisingly, their belief that tobacco use is a morality issue changed from neutral to mild agreement. Given the responsiveness of participants, faith-based leaders are promising vehicles for delivering tobacco use prevention messages. PMID- 17338487 TI - Persistent smoking among Northern Plains Indians: lenient attitudes, low harm value, and partiality toward cigarette smoking. AB - Smoking rates among American Indian youth and adults are the highest in the nation. Funded by the University of Minnesota Cancer Center, the Tobacco Policies Among Plains Indians Project held focus groups on seven reservations during 2001 2002. Members of three Ojibwe reservations in Minnesota, three Sioux reservations in South Dakota, and one Winnebago reservation in Nebraska participated. Areas investigated included smoking knowledge, initiation, attitudes and behaviors, and perceptions of harm. Findings indicate that lenient attitudes toward smoking behaviors, low harm value, and partiality toward the smoking habit and the ritualistic behavior it invokes are long-standing and powerful to overcome. To initiate interventions for persistent smoking, tribes will need to target efforts toward the creation of healthy communities. PMID- 17338488 TI - Needs assessment of Standing Rock elders. AB - This paper describes the results from a needs assessment of American Indian elders residing on the Standing Rock Reservation in the Dakotas. Interviews were conducted by indigenous interviewers with 187 elders aged 49 to 90. Three scales were included: the Iowa Self-Assessment Inventory, the Family APGAR, and the General Self-Efficacy Scale. Findings revealed a high degree of economic stress, high levels of chronic illness and physical disability, and problems in accessing medical care and medicine. The importance of the role of the extended family in coping with problems needs to be considered in the development of health-related programs. PMID- 17338489 TI - Listening to the experts: provider recommendations on the health needs of immigrants and refugees. AB - The purpose of this qualitative, exploratory study was to better understand the needs of immigrants and refugees and how they are affected by poverty and post immigration stresses. Data were obtained through in-depth interviews with 62 health and social service providers working with immigrants in the state of Minnesota. Although the state is home to many refugees who were victims of torture or severe deprivation in their home countries, the majority of providers defined the principal needs of their clients as affordable housing, jobs, and access to health services rather than needs related to health conditions or services per se. The providers' open-ended comments painted a picture of the ways in which post-immigration experiences lead to tangible stresses that compromise immigrants' health and well-being. PMID- 17338490 TI - Race, gender, and cardiovascular disease: do disparities exist at hospitals that serve majority black populations when patients present with ischemic heart disease and myocardial infarction? AB - A retrospective review of data was conducted to determine whether disparities in cardiovascular disease treatment occurred in three public teaching hospitals in Louisiana when patients presented for care with ischemic heart disease (IHD) or acute myocardial infarction (MI). Multinomial logit models were used to estimate the adjusted odds in the utilization of invasive procedures, while controlling for confounders (i.e., age, marital status, comorbidities, payer type, diabetes, and cigarette addiction) simultaneously. No significant racial disparities were found for cardiac catheterization (CC) or Percutaneous Transluminal Coronary Angioplasty (PTCA). However, Blacks had a lower adjusted odds ratio (p < .05) for coronary artery bypass graft surgery (CABG) than did Whites. Furthermore, models failed to show significant gender disparities for invasive procedure utilizations. These disparities, or lack of, may be partially due to patient demographic characteristics or study limitations. Future research should focus on physician referrals and patient preferences. PMID- 17338491 TI - Reduce stress: a stress reduction project for pregnant black women. AB - Approximately 12% of pregnant Black women deliver prematurely regardless of their age, education, income, or marital status. Stress has been indicated as a cause of preterm labor. This article reports on a project that evaluated the effectiveness of a community-based project designed to decrease stress among pregnant Black women. The program evaluation revealed that 86 pregnant Black women of various ages as well as educational and income levels had significant (p = .003) reduction in perceived stress, and their mean post-intervention salivary cortisol (a biological indicator of stress) did not show the expected 50% increase. Lessons learned from this community-based project suggest that three one-on-one educational sessions can reduce stress in this population. PMID- 17338492 TI - Cultural competency among school health educators. AB - Changing demographics in the American classroom make it imperative for school health educators to possess the ability to deliver health education in a manner that takes into account students' cultural backgrounds and practices. The purpose of this article is to describe the level of cultural competence among school health educators and to provide some strategies by which these educators can enhance their cultural competency. Findings from this study show that educators have cultural awareness but illustrate the need for more research in this area in order to understand and increase cultural competency among school health educators. PMID- 17338493 TI - A tribute to Roxanne Struthers, PhD, RN, CTN. PMID- 17338494 TI - [Genitourinary lymphomas]. AB - Lymphomas of the genitourinary tract represent rare tumours for which the diagnosis is crucial regarding the specificity of the treatment. The most frequent localisations are the kidney (solitary tumour or multiple nodules) and the testis; other sites of the genitourinary tract are uncommon. One of the main challenges is to obtain an appropriate immunohistochemical diagnosis with a good staging which is necessary to adapt the therapeutic options. These are mostly based on chemotherapy (with immunotherapy in B-cell lymphomas), of which the intensity and number of cycles depend on initial prognosis factors. PMID- 17338495 TI - [Male infertility: management strategies]. AB - Although the objective of the urologist is to correct the factors of male infertility and to favour natural procreation, the strategy must consider also the couple and the female aspects of infertility. Some types of male infertility require specific treatment. In severe cases, recent advances in medical assistance to procreation have changed the prognosis of male infertility. Pregnancy can be obtained by the means of gamet manipulation and spermatozoid selection. Nevertheless, such techniques expose to genetic disorders transmission. Subsequently, genetic assessment is required during male infertility management, especially for difficult cases. PMID- 17338496 TI - [Conservative treatment of upper urinary tract tumours]. AB - The conservative management of kidney cancer is widely accepted as a therapeutic option for tumours measuring less than 4 cm or in case of underlying renal disease and solitary kidney. The functional and carcinologic success of this conservative treatment results from a radical resection of the tumour and a careful repair of the collecting system and selective ligature of the vessels. Kidney artery clamping is a key to reach these objectives. The cooling of the kidney preserves from warm ischemia and reperfusion lesions. In this review, we explain the physiological basis of warm ischemia induced kidney lesions due to the kidney artery clamping and the advantage of hypothermia. The surgical technique as described by Novick is detailed. This well standardized technique has the advantage of being reproducible and adaptable to all situations. PMID- 17338497 TI - [Technical aspects of nerve sparing during retropubic prostatectomy]. AB - Retropubic radical prostatectomy is the most commonly used therapeutic option for the treatment of clinically localized prostate cancer. An ongoing stage migration towards organ-confined cancers allows performing a nerve-sparing procedure in a growing number of patients. Key elements for achieving convincing functional results are a sphincter preserving Ligation of the distal part of Santorini's plexus and the subtle preparation of the neurovascular bundle. This article gives a detailed description of the operative technique. Furthermore, a strategy for patient selection and tumour selection for the indication of nerve-sparing radical prostatectomy (NSRP) is suggested. PMID- 17338498 TI - [Management of vaginal vault prolapse repair with robotically-assisted laparoscopic sacrocolpopexy]. AB - Transabdominal sacrocolpopexy offers an excellent definitive treatment option for patients with high grade vaginal vault prolapse with long-term success rates ranging from 93-99%. However, because it is a transabdominal procedure it is associated with increased morbidity compared with vaginal repairs. We describe a novel minimally invasive technique of vaginal vault prolapse repair and present out initial experience. The surgical technique involves placement of five laparoscopic ports: three for the Da Vinci robot and two for the assistant. A polypropylene mesh is then attached to the sacral promontory and to the vaginal apex using Gortex sutures. At the end of the case, the mesh material is the covered by the peritoneum. We also present our initial experience with this technique in 18 consecutive patients. The analysis focused on complications, urinary continence, patient satisfaction, and morbidity. Follow-up was conducted by provider-patient interview. Twenty-five patients underwent a robotic-assisted laparoscopic sacrocolpopexy at our institution in the past 24 months for severe symptomatic vaginal vault prolapse. 10/25 (40%) underwent a concomitant anti incontinence procedure. Mean follow-up was 5. (1-12) months and mean age was 66 (47-82) years. Mean total operative time was 3.2 (2.25-4.75) hours. One patient had to be converted to an open procedure secondary to unfavorable anatomy. All but one patient were discharged from the hospital after an overnight stay; one patient left on postoperative day #2. Complications were limited to mild port site infections in two patients, which resolved with oral antibiotic therapy. One patient developed recurrent grade 3 rectocele, but had no evidence of cystocele or enterocele. We present a novel technique for vaginal vault prolapse repair that combines the advantages of open sacrocolpopexy with the decreased morbidity and improved cosmesis of laparoscopic surgery. It is associated with decreased hospital stay, low complication and conversion rates, and high patient satisfaction. While our early experience is encouraging, long-term data is needed to confirm these findings and establish longevity of the repair. PMID- 17338499 TI - [Conservative treatment of upper urinary tract tumors]. AB - The histological appearance and the clinical behaviour of upper urinary tract urothelial tumours are almost identical to those of the bladder. Superficial papillary tumours rarely progress and turn to invasive disease despite a high frequency of recurrence. Technical developments in the endourology field have allowed full endoscopic access to upper tract tumours. Endoscopic resection or ablation of the tumour can be undertaken safely and effectively through ureteroscopy or percutaneous nephroscopy with low risk of extra-renal tumour seeding. For superficial (Ta, T1), low grade (I, II) tumours, a conservative approach can be selected without compromising survival and prognosis. For muscle invasive > T2 or high grade (III) tumours, nephroureterectomy remains the treatment of choice. Intracavitary BCG used after percutaneous resection reduces the risk of recurrence of upper tract urothelial tumours regardless of the grade. Finally, the world literature and our personal experience have shown that the tumour grade and stage are the two independent factors that affect survival of patients with upper urinary tract tumours. PMID- 17338500 TI - Effect of nanoparticle sizes and number densities on the evaporation and dryout characteristics for strongly pinned nanofluid droplets. AB - A microfabricated linear heater array operating in a constant voltage mode has been used to study the effect of nanoparticle size on the evaporation and dryout characteristics of strongly pinned nanofluid droplets. Four different nanofluids have been tested, containing 2-nm Au, 30-nm CuO, 11-nm Al2O3, and 47-nm Al2O3 nanoparticles, each of 5-muL droplets with 0.5 vol % in water. Nanofluid droplets show strong pinning along the droplet perimeter and, upon evaporation, leave a ring-shaped nanoparticle stain. Particle size is seen to have a clear and strong effect on the dryout stain pattern, while heater temperature seems to have little effect. With the assumption of axi-symmetry, tomographic deconvolution of measured data from the linear heater array allows for examination of the spatially and temporally resolved temperature and heat flux characteristics of the evaporating nanofluid droplets. PMID- 17338501 TI - Mechanism of generation of volatile hydrides of trace elements by aqueous tetrahydroborate(III). Mass spectrometric studies on reaction products and intermediates. AB - The mechanism of generation of volatile metal/metalloid hydrides by derivatization with borane complexes is presented. This reaction has been employed for ultratrace element analysis since 1972 and has been the source of much controversy in regard to the reaction mechanism. Here we investigated this derivatization by using As(III), Sb(III), Bi(III), MeAsO(OH)2, and Me2AsO(OH) as model analytes and NaBH4, NaBD4, tert-BuNH2BH3, and Me2NHBH3 as borane reagents. The identification of reaction products and intermediates observed under various reaction conditions was performed by gas chromatography/mass spectrometry and electrospray ionization mass spectrometry. An alternative reaction model, based on the formation of analyte-borane complex (ABC) intermediates, is able to reconcile all the experimental evidence reported in the literature. In this study, we provide definitive evidence of the ABC hydride generation mechanism, which shows that the generation of volatile hydrides occurs via formation of ABC intermediates between hydroboron species and the analyte substrate followed by the direct transfer of hydrogen from boron to the analyte atom, and fast hydrolysis leading to the final product. PMID- 17338502 TI - Analysis of freely dissolved alcohol ethoxylate homologues in various seawater matrixes using solid-phase microextraction. AB - Solid-phase microextraction fibers (SPME) were tested as tools to determine freely dissolved alcohol ethoxylate (AE) surfactants in seawater matrixes. Partitioning of a wide range of AE homologues into a 35-mum polyacrylate fiber coating was linearly related to aqueous concentrations as low as submicrograms per liter, with high reproducibility. The exposure time needed to reach equilibrium between aqueous phase and the SPME fiber depended on the fiber-water partitioning coefficient (Kfw) of the AE homologue. Specific attention was given to the influence of various matrixes on the analysis via SPME. The presence of sediment increases the uptake kinetics of AE homologues for which diffusion in the aqueous phase is rate limiting. The Kfw in equilibrated systems was not affected by the presence of other homologues, micelles, or varying amounts of sediment phase. SPME is therefore a suitable tool for analysis of AE in sorption studies and sediment toxicity tests. A strong linear relation was observed between Kfw and the hydrophobicity of the AE homologue, using estimated octanol water partition coefficients. This relation can be used to predict the partitioning coefficient of any AE homologue to the SPME fiber, which facilitates the analysis of complex mixtures. PMID- 17338503 TI - Using a multijunction microfluidic device to inject substrate into an array of preformed plugs without cross-contamination: comparing theory and experiments. AB - In this paper we describe a multijunction microfluidic device for the injection of a substrate into an array of preformed plugs carried by an immiscible fluid in a microchannel. The device uses multiple junctions to inject substrate into preformed plugs without synchronization of the flow of substrate and the array of preformed plugs of reagent, which reduces cross-contamination of the plugs, eliminates formation of small droplets of substrate, and allows a greater range of injection ratios compared to that of a single T-junction. The device was based on a previously developed physical model for transport that was here adapted to describe injection and experimentally verified. After characterization, the device was applied to two biochemical assays, including evaluation of the enzymatic activity of thrombin and determination of the coagulation time of human blood plasma, which both provided reliable results. The reduction of cross contamination and greater range of injection ratios achieved by this device may improve the processes that involve addition and titration of reagents into plugs, such as high-throughput screening of protein crystallization conditions. PMID- 17338504 TI - Thin-layer chromatography/desorption electrospray ionization mass spectrometry: investigation of goldenseal alkaloids. AB - Desorption electrospray ionization mass spectrometry was investigated as a means to qualitatively identify and to quantify analytes directly from developed normal phase thin-layer chromatography plates. The atmospheric sampling capillary of a commercial ion trap mass spectrometer was extended to permit sampling and ionization of analytes in bands separated on intact TLC plates (up to 10 cmx10 cm). A surface positioning software package and the appropriate hardware enabled computer-controlled surface scanning along the length of development lanes or at fixed Rf value across the plates versus the stationary desorption electrospray emitter. Goldenseal (Hydrastis canadensis) and related alkaloids and commercial dietary supplements were used as standards and samples. Alkaloid standards and samples were spotted and separated on aluminum- or glass-backed plates using established literature methods. The mass spectral signal levels as a function of desorption spray solvent were investigated with acetonitrile proving superior to methanol. The detection levels (approximately 5 ng each or 14-28 pmol) in mass spectral full-scan mode were determined statistically from the calibration curves (2.5-100 pmol) for the standards berberine, palmatine, and hydrastinine spotted as a mixture and separated on the plates. Qualitative screening of the major alkaloids present in six different over-the-counter "goldenseal" dietary supplements was accomplished by obtaining full-scan mass spectra during surface scans along the development lane in the direction of increasing Rf value. In one sample, alkaloids were detected that strongly suggested the presence of at least one additional herb undeclared on the product label. These same data indicated the misidentification of one of the alkaloids in the TLC literature. Quantities of the alkaloids present in two of the samples determined using the mass spectral data were in reasonable agreement with the label values, indicating the quantitative ability of the method. The advantage of mass spectral measurements in identifying and quantifying materials within overlapping bands and in providing positive identification for even minor species in a mixture was also demonstrated. PMID- 17338505 TI - Reusable electrochemical sensing platform for highly sensitive detection of small molecules based on structure-switching signaling aptamers. AB - Aptamers are nucleic acids that have high affinity and selectivity for their target molecules. A target may induce the structure switching from a DNA/DNA duplex to a DNA/target complex. In the present study, a reusable electrochemical sensing platform based on structure-switching signaling aptamers for highly sensitive detection of small molecules is developed using adenosine as a model analyte. A gold electrode is first modified with polytyramine and gold nanoparticles. Then, thiolated capture probe is assembled onto the modified electrode surface via sulfur-gold affinity. Ferrocene (Fc)-labeled aptamer probe, which is designed to hybridize with capture DNA sequence and specifically recognize adenosine, is immobilized on the electrode surface by hybridization reaction. The introduction of adenosine triggers structure switching of the aptamer. As a result, Fc-labeled aptamer probe is forced to dissociate from the sensing interface, resulting in a decrease in redox current. The decrement of peak current is proportional to the amount of adenosine. The present sensing system could provide both a wide linear dynamic range and a low detection limit. In addition, high selectivity, good reproducibility, stability, and reusability are achieved. The recovery test demonstrates the feasibility of the designed sensing system for an adenosine assay. PMID- 17338506 TI - Enhancing sensitivity in headspace-mass spectrometric determination of BTEX in drinking water. AB - A way to extract useful chemical information from the volatile profile provided by a headspace-mass spectrometer (HS-MS) is developed in order to improve sensitivity in HS-MS analysis. The methodology is based on the selection of a narrow window in the volatile profile where the signal-to-noise ratio was maximal by combining the data acquisition time and scan rate. To test this approach, benzene, toluene, ethylbenzene, and p-xylene (BTEX) as well as their mixtures were quantified in drinking waters. Individual hydrocarbons were determined between 1 and 30 microg/L (mean RSD, 4.0% for 10 microg/L) while mixtures were quantified at a microgram per liter level by using the partial least-squares multivariate algorithm with a relative standard prediction error of under 3.5%. These results indicate that the method proposed is useful as a sensitive and selective tool for the determination of BTEX and surpasses other reported HS-MS alternatives. In addition, the proposed methodology can be extended to others that insert analytes from a sample directly into a MS, such as membrane introduction mass spectrometry among others. PMID- 17338507 TI - Raman chemical imaging spectroscopy reagentless detection and identification of pathogens: signature development and evaluation. AB - An optical detection method, Raman chemical imaging spectroscopy (RCIS), is reported, which combines Raman spectroscopy, fluorescence spectroscopy, and digital imaging. Using this method, trace levels of biothreat organisms are detected in the presence of complex environmental backgrounds without the use of amplification or enhancement techniques. RCIS is reliant upon the use of Raman signatures and automated recognition algorithms to perform species-level identification. The rationale and steps for constructing a pathogen Raman signature library are described, as well as the first reported Raman spectra from live, priority pathogens, including Bacillus anthracis, Yersinia pestis, Burkholderia mallei, Francisella tularensis, Brucella abortus, and ricin. Results from a government-managed blind trial evaluation of the signature library demonstrated excellent specificity under controlled laboratory conditions. PMID- 17338508 TI - Factor Xa inhibitors: S1 binding interactions of a series of N-{(3S)-1-[(1S)-1 methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides. AB - Factor Xa inhibitory activities for a series of N-{(3S)-1-[(1S)-1-methyl-2 morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides with different P1 groups are described. These data provide insight into binding interactions within the S1 primary specificity pocket; rationales are presented for the derived SAR on the basis of electronic interactions through crystal structures of fXa-ligand complexes and molecular modeling studies. A good correlation between in vitro anticoagulant activities with lipophilicity and the extent of human serum albumin binding is observed within this series of potent fXa inhibitors. Pharmacokinetic profiles in rat and dog, together with selectivity over other trypsin-like serine proteases, identified 1f as a candidate for further evaluation. PMID- 17338509 TI - One- to four-dimensional kernels for virtual screening and the prediction of physical, chemical, and biological properties. AB - Many chemoinformatics applications, including high-throughput virtual screening, benefit from being able to rapidly predict the physical, chemical, and biological properties of small molecules to screen large repositories and identify suitable candidates. When training sets are available, machine learning methods provide an effective alternative to ab initio methods for these predictions. Here, we leverage rich molecular representations including 1D SMILES strings, 2D graphs of bonds, and 3D coordinates to derive efficient machine learning kernels to address regression problems. We further expand the library of available spectral kernels for small molecules developed for classification problems to include 2.5D surface and 3D kernels using Delaunay tetrahedrization and other techniques from computational geometry, 3D pharmacophore kernels, and 3.5D or 4D kernels capable of taking into account multiple molecular configurations, such as conformers. The kernels are comprehensively tested using cross-validation and redundancy reduction methods on regression problems using several available data sets to predict boiling points, melting points, aqueous solubility, octanol/water partition coefficients, and biological activity with state-of-the art results. When sufficient training data are available, 2D spectral kernels in general tend to yield the best and most robust results, better than state-of-the art. On data sets containing thousands of molecules, the kernels achieve a squared correlation coefficient of 0.91 for aqueous solubility prediction and 0.94 for octanol/water partition coefficient prediction. Averaging over conformations improves the performance of kernels based on the three-dimensional structure of molecules, especially on challenging data sets. Kernel predictors for aqueous solubility (kSOL), LogP (kLOGP), and melting point (kMELT) are available over the Web through: http://cdb.ics.uci.edu. PMID- 17338510 TI - Three-dimensional quantitative structure-activity relationship of nucleosides acting at the A3 adenosine receptor: analysis of binding and relative efficacy. AB - The binding affinity and relative maximal efficacy of human A3 adenosine receptor (AR) agonists were each subjected to ligand-based three-dimensional quantitative structure-activity relationship analysis. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) used as training sets a series of 91 structurally diverse adenosine analogues with modifications at the N6 and C2 positions of the adenine ring and at the 3', 4', and 5' positions of the ribose moiety. The CoMFA and CoMSIA models yielded significant cross-validated q2 values of 0.53 (r2 = 0.92) and 0.59 (r2 = 0.92), respectively, and were further validated by an external test set (25 adenosine derivatives), resulting in the best predictive r2 values of 0.84 and 0.70 in each model. Both the CoMFA and the CoMSIA maps for steric or hydrophobic, electrostatic, and hydrogen-bonding interactions well reflected the nature of the putative binding site previously obtained by molecular docking. A conformationally restricted bulky group at the N6 or C2 position of the adenine ring and a hydrophilic and/or H-bonding group at the 5' position were predicted to increase A3AR binding affinity. A small hydrophobic group at N6 promotes receptor activation. A hydrophilic and hydrogen-bonding moiety at the 5' position appears to contribute to the receptor activation process, associated with the conformational change of transmembrane domains 5, 6, and 7. The 3D-CoMFA/CoMSIA model correlates well with previous receptor-docking results, current data of A3AR agonists, and the successful conversion of the A3AR agonist into antagonists by substitution (at N6) or conformational constraint (at 5'-N-methyluronamide). PMID- 17338513 TI - Nitrogen-rich carbon nitride network materials via the thermal decomposition of 2,5,8-triazido-s-heptazine. AB - This report describes the rapid and slow thermal decomposition of an energetically unstable polycyclic and heterocyclic azide, triazido-s-heptazine (C6N16), to produce nitrogen-rich CNx materials (x > 1.2). An analysis of gaseous byproducts shows that this large heterocyclic precursor releases primarily N2 gas during its decomposition. The product composition and its morphology are dependent on the rapidity of the TAH decomposition. The CNx products are thermally stable to 500 degrees C and exhibit variations in H and O content dependent on precursor preparation and atmospheric exposure. The rapid decomposition of TAH leads to visibly porous powders, while slow decomposition yields smooth monoliths that are reminiscent of the morphology of the starting polycrystalline powder. IR and NMR spectral similarities between the amorphous CNx products and several previously reported heptazine molecules and extended heptazine networks supports significant retention of heptazine motif in these amorphous carbon nitride extended materials. PMID- 17338514 TI - Synthesis of CeO2 nanorods via ultrasonication assisted by polyethylene glycol. AB - Polycrystalline CeO2 nanorods 5-10 nm in diameter and 50-150 nm in length were synthesized via ultrasonication using polyethylene glycol (PEG) as a structure directing agent at room temperature. The properties of the CeO2 nanorods were characterized by TEM, EDS, XRD, XPS, FT-IR, TG, BET, and UV-vis spectroscopy. Various reaction parameters, such as the content of PEG, the molecular weight of PEG, the concentration of KOH, the pH value, and the sonication time, were investigated by a series of control experiments. The content of PEG, the molecular weight of PEG, and the sonication time were confirmed to be the crucial factors determining the formation of one-dimensional CeO2 nanorods. A possible ultrasonic formation mechanism has been suggested to explain the formation of CeO2 nanorods. PMID- 17338515 TI - Structural and magnetic properties of MCl2 (M = Fe, Mn, Co): acetonitrile solvates. AB - MIICl2 (M = Mn, Fe, Co) as their acetonitrile solvates were isolated, and their structural, spectroscopic, and magnetic properties were studied. MCl2(NCMe)2 (M = Fe, Mn) form 1-D chains of octahedral MII ions with four bridging chlorides and two axial MeCN's. The presence of an axial distortion for MFe causes a significant magnetic anisotropy that increases significantly below 150 K; however, chiav [=(chi parallel + 2chi perpendicular)/3] almost coincides with the value obtained on a polycrystalline sample. MnCl2(NCMe)2 is a paramagnet with a weak antiferromagnetic coupling. Annealing FeCl2(NCMe)2 at 55 degrees C forms the monosolvate of FeCl2(NCMe) composition in which two chains collapse into a double chain with formation of Fe-Cl bonding such that half of the mu-Cl's becomes mu3 Cl's. This material orders magnetically below Tc = 4.3 K. For M = Co, paramagnetic tetrahedral [CoCl3(NCMe)]- anions are isolated. PMID- 17338516 TI - Boron-pnictogen multiple bonds: donor-stabilized P=B and As=B bonds and a hindered iminoborane with a B-N triple bond. AB - Reaction of the hindered phosphino- and arsinoboranes, Ar*Pn(H)-B(Br)Tmp (Ar* = C6H3-2,6-(C6H2-2,4,6-iPr3)2; Tmp = 2,2,6,6-tetramethylpiperidino; Pn = P and As, 1 and 3, respectively) with 4-dimethylaminopyridine, DMAP, afforded the boranylidenephosphane and arsane, Ar*Pn=B(DMAP)Tmp (Pn = P and As, 2 and 4) as deep red-purple solids. The analogous aminoboranes Ar'N(H)-B(X)Tmp (Ar' = -C6H3 2,6-(C6H2-2,4,6-Me3)2; X = Cl and Br; 5 and 6) did not display any reactivity with DMAP, but in the presence of the amide base, Na[N(SiMe3)2], the clean formation of the uncomplexed iminoborane Ar'NBTmp (7) was observed. Attempts to generate an Sb=B bond were unsuccessful, as the required stibinoborane precursor, Ar*Sb(H)-B(Br)Tmp, could not be prepared; in place of clean Sb-B bond formation, the reduced product Ar*Sb=SbAr* was obtained. All compounds were characterized spectroscopically, and the X-ray crystal structures of 1, 2, 4, 6, and 7 were determined. PMID- 17338517 TI - A series of [3 + 2] cycloaddition products from the reaction of rhenium oxo complexes with diphenyl ketene. AB - The reaction of rhenium (VII) trioxo complexes containing the ligand sets scorpionate, [HB(pz)3]ReO3 (6), [Ph-B(pz)3]ReO3 (7), and [[HC(pz)3]ReO3][ReO4] (8) and pyridine/pyridine-type ligands [(4,7-diphenyl-1,10-phen)(Br)ReO3] (12), [(4,4'-di-tert-butyl-2,2'-dipyridyl)(Cl)ReO3] (13), and [(py)2Re(Cl)O3] (4), with diphenyl ketene, has led to the isolation of six novel [3 + 2] cycloaddition products. These air-stable solids 9-11 and 15-17 are the result of [3 + 2] addition of the O=Re=O motif across the ketene C=C double bond. Five of the six [3 + 2] cycloaddition products have been structurally characterized by single crystal X-ray diffraction and in all cases by 13C NMR and IR spectroscopies. PMID- 17338518 TI - Monodisperse and core-shell-structured SiO2@YBO3:Eu3+ spherical particles: synthesis and characterization. AB - Y0.9Eu0.1BO3 phosphor layers were deposited on monodisperse SiO2 particles of different sizes (300, 570, 900, and 1200 nm) via a sol-gel process, resulting in the formation of core-shell-structured SiO2@Y0.9Eu0.1BO3 particles. X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), photoluminescence (PL), and cathodoluminescence (CL) spectra as well as lifetimes were employed to characterize the resulting composite particles. The results of XRD, FE-SEM, and TEM indicate that the 800 degrees C annealed sample consists of crystalline YBO3 shells and amorphous SiO2 cores, in spherical shape with a narrow size distribution. Under UV (240 nm) and VUV (172 nm) light or electron beam (1-6 kV) excitation, these particles show the characteristic 5D0-7F1-4 orange-red emission lines of Eu3+ with a quantum yield ranging from 36% (one-layer Y0.9Eu0.1BO3 on SiO2) to 54% (four-layer Y0.9Eu0.1BO3 on SiO2). The luminescence properties (emission intensity and color coordinates) of Eu3+ ions in the core-shell particles can be tuned by the coating number of Y0.9Eu0.1BO3 layers and SiO2 core particle size to some extent, pointing out the great potential for these particles applied in displaying and lightening fields. PMID- 17338519 TI - Addition of S-H bonds across electron-deficient olefins catalyzed by well-defined copper(I) thiolate complexes. AB - A series of monomeric (NHC)Cu(SR) (R = Ph or CH2Ph; NHC = N-heterocyclic carbene) complexes have been synthesized and fully characterized including single-crystal X-ray diffraction studies. These complexes catalyze the addition of S-H bonds across electron-deficient olefins to regioselectively produce "anti-Markovnikov" products. PMID- 17338520 TI - Chiral separation: mechanism modeling in two-dimensional systems. AB - Fluid phase separations of racemates are difficult because the subtle, short ranged differences in intermolecular interactions of like and unlike pairs of chiral molecules are typically smaller than the thermal energy. A surface restricts the configurational space available to the pair of interacting molecules, thus changing the effective interactions between them. Because of this restriction, a surface can promote chiral separation of mixtures that are racemic in bulk. In this paper, we investigate chiral symmetry breaking induced by an achiral surface in a racemate. A parallel tempering Monte Carlo algorithm with tempering over the temperature domain is used to examine the interplay between molecular geometry and energetics in promoting chiral separations. The system is restricted to evolve in two dimensions. By controlling the balance between electrostatic and steric interactions, one can direct the surface assembly of the chiral molecules toward formation of small clusters of identical molecules. When molecular shape asymmetry is complemented by dipolar alignment, chiral micellar clusters of like molecules are assembled on the surface. We examine the case of small model molecules for which the two-dimensional restriction of the pair potential is sufficient to induce chiral segregation. An increase in molecular complexity can change the balance of intermolecular interactions to the point that heterochiral pairs are energetically more favored. In this case, we find conditions in which formation of homochiral micelles is still achieved, due to a combination of multibody and entropic effects. In such systems, an examination of the pair potential alone is insufficient to predict whether the multimolecular racemate will or will not segregate. PMID- 17338521 TI - Reactions of nitrogen oxides with the five-coordinate Fe(III)(porphyrin) nitrito intermediate Fe(Por)(ONO) in sublimed solids. AB - Detailed experimental studies are described for reactions of several nitrogen oxides with iron porphyrin models for heme/NxOy systems. It is shown by FTIR and optical spectroscopy and by isotope labeling experiments that reaction of small increments of NO2 with sublimed thin layers of the iron(II) complex Fe(Por) (Por = meso-tetraphenylporphyrinato dianion, TPP, or meso-tetra-p-tolylporphyrinato dianion, TTP) leads to formation of the 5-coordinate nitrito complexes Fe(Por)(eta1-ONO) (1), which are fairly stable but very slowly decompose under vacuum giving mostly the corresponding nitrosyl complexes Fe(Por)(NO). Further reaction of 1 with new NO2 increments leads to formation of the nitrato complex Fe(Por)(eta2-O2NO) (2). The interaction of NO with 1 at low temperature involves ligand addition to give the nitrito-nitrosyl complexes Fe(Por)(eta1-ONO)(NO) (3); however, these isomerize to the nitro-nitrosyl analogs Fe(Por)(eta1-NO2)(NO) (4) upon warming. Experiments with labeled nitrogen oxides argue for an intramolecular isomerization ("flipping") mechanism rather than one involving dissociation and rebinding of NO2. The Fe(III) centers in the 6-coordinate species 3 and 4 are low spin in contrast to 1, which appears to be high-spin, although DFT computations of the porphinato models Fe(P)(nitrite) suggest that the doublet nitro species and the quartet and sextet nitrito complexes are all relatively close in energy. The nitro-nitrosyl complex 4 is stable under an NO atmosphere but decomposes under intense pumping to give a mixture of the ferrous nitrosyl complex Fe(Por)(NO) and the ferric nitrito complex Fe(Por)(eta1-ONO) indicating the competitive dissociation of NO and NO2. Hence, loss of NO from 4 is accompanied with nitro --> nitrito isomerization consistent with 1 being the more stable of the 5-coordinate NO2 complexes of iron porphyrins. PMID- 17338522 TI - Site-specific incorporation of glycosylated serine and tyrosine derivatives into proteins. AB - Glycosylation of proteins can have a dramatic effect on their physical, chemical, and biological properties. Analogues of dihydrofolate reductase and firefly luciferase containing glycosylated amino acids at single, predetermined sites have been elaborated. Misacylated suppressor tRNAs activated with glycosylated serine and tyrosine derivatives were used for suppression of the nonsense codons in a cell-free protein biosynthesizing system, thereby permitting the preparation of the desired glycosylated proteins. In this fashion, it was possible to obtain proteins containing both mono- and diglycosylated amino acids, including glycosylated serine and tyrosine moieties. For the modified firefly luciferases, the effect of these substitutions on the wavelength of the light emitted by firefly luciferase was investigated. The maximum wavelength for mutants containing peracetylated glycosylated serine derivatives at position 284 showed a red shift in the emission spectra. For mutants containing glycosylated tyrosines, the red shift was observed only when the carbohydrate moiety was fully deacetylated. PMID- 17338523 TI - Design and synthesis of molecules with switchable chirality via formation and cleavage of metal-ligand coordination bonds. PMID- 17338524 TI - Ion pair recognition of quaternary ammonium and iminium salts by uranyl-salophen compounds in solution and in the solid state. AB - Efficient ditopic receptors for quaternary ammonium and iminium salts have been obtained upon functionalization of the uranyl-salophen unit with conformationally flexible side arms bearing phenyl or beta-naphthyl substituents. Binding affinities in chloroform solution have been measured for a large number of quaternary salts comprising tetramethylammonium (TMA), tetrabutylammonium (TBA), acetylcholine (ACh), N-methylpyridinium (NMP), and N-methylisoquinolinium (NmiQ) cations. Recognition of the anion partner is ensured by coordination to the hard Lewis acidic uranyl center, whereas cation-pi/CH-pi interactions of the quaternary ions are established with the aromatic pendants. The role of the cation-anion interactions on the dynamics of exchange between the free and complexed species is discussed. Solid-state structures have been obtained for a few salt-receptor combinations. In the solid state, side-armed receptor molecules form assemblies that enclose ion pair aggregates of varying composition and structure, including AChCl dimers, two different kinds of tetrameric (TMA)Cl clusters, and unidimentional salt strips of (NMP)Br. The lack of side arms as preferential binding sites for the polar quaternary cations prevents association patterns of the kinds formed with the side-armed receptors, as shown by the crystal structure of the complex of (TMA)Cl with the parent uranyl-salophen receptor. PMID- 17338525 TI - Shear instabilities in metallic nanoparticles: hydrogen-stabilized structure of Pt37 on carbon. AB - Using density functional theory calculations, we have studied the morphology of a Pt37 nanoparticle supported on carbon with and without hydrogen (H) passivation that arises with postprocessing of nanoparticles before characterization. Upon heating in an anneal cycle, we find that without H (e.g., in a helium atmosphere or evacuation at high temperature), the morphology change of a truncated cuboctahedral Pt37 is driven by the shearing of (100) to (111) facets to lower the surface energy, a remnant shear instability that drives surface reconstruction in semi-infinite Pt(100). With H passivation from a postprocessing anneal, we show that the sheared structure automatically reverts to the observed truncated cuboctahedral structure and the average first nearest-neighbor Pt-Pt bond length increases by 3%, agreeing well with experiment. We explain the stabilization of the truncated cuboctahedral structure due to H passivation via adsorption energetics of hydrogen on Pt(100) and (111) facets, specifically, the preference for H adsorption at bridge sites on (100) facets, which should be considered in a realistic model for H adsorption on Pt nanoparticles. We find that dramatic morphological change of a nanoparticle can occur even with small changes to first-shell Pt-Pt coordination number. The implications of our findings when comparing to experimental data are discussed. PMID- 17338526 TI - Patterned deposition of a mixed-coordination adenine-silver helicate, containing a pi-stacked metallacycle, on a graphite surface. PMID- 17338527 TI - Continuum of outer- and inner-sphere mechanisms for organic electron transfer. Steric modulation of the precursor complex in paramagnetic (ion-radical) self exchanges. AB - Transient 1:1 precursor complexes for intermolecular self-exchange between various organic electron donors (D) and their paramagnetic cation radicals (D+*), as well as between different electron acceptors (A) paired with their anion radicals (A-*), are spectrally (UV-NIR) observed and structurally (X-ray) identified as the cofacial (pi-stacked) associates [D, D+*] and [A-*, A], respectively. Mulliken-Hush (two-state) analysis of their diagnostic intervalence bands affords the electronic coupling elements (HDA), which together with the Marcus reorganization energies (lambda) from the NIR spectral data are confirmed by molecular-orbital computations. The HDA values are found to be a sensitive function of the bulky substituents surrounding the redox centers. As a result, the steric modulation of the donor/acceptor separation (rDA) leads to distinctive electron-transfer rates between sterically hindered donors/acceptors and their more open (unsubstituted) parents. The latter is discussed in the context of a continuous series of outer- and inner-sphere mechanisms for organic electron transfer processes in a manner originally formulated by Taube and co-workers for inorganic (coordination) donor/acceptor dyads-with conciliatory attention paid to traditional organic versus inorganic concepts. PMID- 17338528 TI - Bis(phenyl)dirhodium(III) caprolactamate: a dinuclear paddlewheel complex with no metal-metal bond. PMID- 17338529 TI - Palladium-catalyzed asymmetric silaborative C-C cleavage of meso methylenecyclopropanes. PMID- 17338532 TI - Total synthesis of (+/-) -phenserine via [4+1] cyclization of a bis(alkylthio)carbene and an indole isocyanate. AB - [structure: see text]. A total synthesis of acetylcholine blocking agent, phenserine, has been achieved by employing a [4+1] cyclization between an appropriately substituted indole isocyanate and a bis(alkylthio)carbene. PMID- 17338534 TI - Stereoselective chemical synthesis of sugar nucleotides via direct displacement of acylated glycosyl bromides. AB - [structure: see text]. The use of Leloir glycosyltransferases to prepare biologically relevant oligosaccharides and glycoconjugates requires access to sugar nucleoside diphosphates, which are notoriously difficult to efficiently synthesize and purify. We report a novel stereoselective route to UDP- and GDP alpha-D-mannose as well as UDP- and GDP-beta-L-fucose via direct displacement of acylated glycosyl bromides with nucleoside 5'-diphosphates. PMID- 17338533 TI - Calyciphylline D, a novel alkaloid with an unprecedented fused-pentacyclic skeleton from Daphniphyllum calycinum. AB - [structure: see text]. Calyciphylline D (1), a novel Daphniphyllum alkaloid with an unprecedented fused-pentacyclic skeleton containing a 8 azatricyclo[4.2.1.0.4,8]nonane ring system, has been isolated from the leaves of Daphniphyllum calycinum (Daphniphyllaceae), and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data. PMID- 17338535 TI - Regio- and stereoselective lithiation and electrophilic substitution reactions of N-Alkyl-2,3-diphenylaziridines: solvent effect. AB - [structure: see text]. The lithiation reaction of cis- and trans-N-alkyl-2,3 diphenylaziridines has been investigated. While cis-diphenylaziridines do not undergo any lithiation upon treatment with organolithiums, the lithiation reaction of the trans counterparts is completely alpha-regioselective and the stereochemical course of the lithiation-trapping sequence is solvent dependent: inversion of configuration in coordinating solvents (THF or toluene/crown ether) and retention in hexane, ether, or toluene. The preparation of stereodefined functionalized N-alkyl-2,3-diphenylaziridines is described. PMID- 17338536 TI - Asymmetric synthesis of the (S)-1,1-dioxido-isothiazolidin-3-one phosphotyrosine mimetic via reduction of a homochiral (R)-oxido-isothiazolidin-3-one. AB - [structure: see text]. The first asymmetric synthesis of the (S)-1,1-dioxido isothiazolidin-3-one ((S)-IZD) pTyr mimetic, which has been incorporated into the recently reported potent protein tyrosine phosphatase 1B (PTP1B) inhibitors, is presented herein. The key reaction is the reduction of the (R)-oxido isothiazolidin-3-one heterocycle with excellent regiochemical and stereochemical control (>98% ee; 82% yield). PMID- 17338537 TI - Concise synthesis of the bacterial DNA primase inhibitor (+) -Sch 642305. AB - [structure: see text]. A highly convergent, enantioselective synthesis of (+) Sch 642305 is presented, which features a Mukaiyama-Michael addition followed by allylation to establish the syn-anti relationship of the three contiguous stereocenters. The 10-membered macrolactone was formed through ring-closing metathesis. PMID- 17338538 TI - Rhodium-catalyzed asymmetric one-pot transesterification and [2 + 2 + 2] cycloaddition leading to enantioenriched 3,3-disubstituted phthalides. AB - [structure: see text]. We have developed a cationic rhodium(I)/Solphos complex catalyzed asymmetric one-pot transesterification and [2 + 2 + 2] cycloaddition of 1,6-diyne esters with tertiary propargylic alcohols leading to enantioenriched tricyclic 3,3-disubstituted phthalides. The present method represents a versatile new route to the synthesis of enantioenriched tricyclic 3,3-disubstituted phthalides in view of the easy access to both coupling partners. PMID- 17338539 TI - Enantioselective total synthesis of 1-epi-pathylactone A. AB - [structure: see text]. The first enantioselective total synthesis of 1-epi pathylactone A, 3, has been accomplished using a PhI(OAc)2-mediated domino reaction as a key step. No diastereomeric separation was required throughout the whole synthetic scheme presented in this paper. Comparison of 1H and 13C NMR spectral data of the synthetic product with the reported spectral data of natural pathylactone A, coupled with an X-ray crystallographic analysis, led to the conclusion that the C1 configuration in the original paper was erroneously ascribed to (R). PMID- 17338540 TI - Facile synthesis of amine-terminated aromatic polyamide dendrimers via a divergent method. AB - [structure: see text]. A novel, rapid, inexpensive, and highly efficient divergent approach for the synthesis of a 32-amine-terminated G4 polyamide dendrimer has been developed. Each generation dendrimer was successfully obtained by the condensation of the preceding generation dendrimer with the building block and the deprotection with hydrazine in one pot. All the dendrimers were easily purified by precipitation in alkaline water, and the purity was confirmed by NMR, MALDI-TOF mass spectra, and elemental analysis. PMID- 17338541 TI - Synthesis of the oxygenated pactamycin core. AB - [structure: see text]. Pactamycin, one of the most complex and densely functionalized aminocyclitol antibiotics known, presents synthetic challenges that include reactivity and sterics, relative and absolute stereochemistry, and functional group compatibility and protection. An approach is reported that features four different types of (cyclopentane) face selective functionalization reactions and results in a polyfunctionalized and appropriately protected intermediate that incorporates all the core carbons and the oxygenated functionality of the target. PMID- 17338542 TI - Palladium-catalyzed anti-hydrothiolation of 1-alkynylphosphines. AB - [structure: see text]. Treatment of 1-alkynylphosphine with thiol in the presence of a catalytic amount of palladium acetate results in regio- and stereoselective anti-hydrothiolation, yielding the corresponding (Z)-1-phosphino-2-thio-1-alkene. PMID- 17338543 TI - Synthesis of (S,R,R,S,R,S)-4,6,8,10,16,18- hexamethyldocosane from Antitrogus parvulus via diastereoselective hydrogenations. AB - [structure: see text]. The hydrocarbon 1 was prepared via a series of catalyst controlled diastereoselective hydrogenations beginning with fragments derived from the Roche ester. PMID- 17338544 TI - Blue fluorescent 4a-Aza-4b-boraphenanthrenes. AB - [structure: see text]. Phenanthrene analogues with internalized B-N moieties were found to afford blue light emission with good quantum efficiencies, whereas the isomeric species with peripheral B-N moieties displayed only UV emission behavior, like the all-carbon framework. PMID- 17338545 TI - Anthocyanone A: a quinone methide derivative resulting from malvidin 3-O glucoside degradation. AB - A new compound resulting from the oxidative degradation of maldivin 3-O-glucoside under acid conditions was detected in a wine model solution stored under 90 and 25 degrees C. It was isolated by semipreparative HPLC, and its structure was elucidated by UV-vis spectra, mass spectrometry (LC/MS), and NMR spectroscopy (1 D and 2-D). The compound was identified as 8-beta-d-glucopyranosyl-2,4-dihydroxy 6-oxo-cyclohexa-2,4-dienyl acetic acid (anthocyanone A), which results from nucleophilic attack of hydrogen peroxide to maldivin 3-O-glucoside through a Baeyer-Villiger oxidation followed by other oxidations steps. PMID- 17338546 TI - Technique for screening immune-enhancing polysaccharides in food using 1,25 dihydroxyvitamin D3-differentiated HL60 cells. AB - A technique for screening immune-enhancing polysaccharides in food using the phagocytotic activity of 1,25-dihydroxyvitamin D3 (VD3)-differentiated HL60 cells is presented. HL60 cells, a human acute promyelocytic cell line, can differentiate along the monocytic lineage following exposure to VD3 or phorbol-12 myristate-13-acetate (PMA). For differentiated cells along the monocytic pathway, HL60 cells were maintained in RPMI 1640 medium supplemented with 10% FBS and 120 nM VD3 for more than 1 week. VD3-differentiated HL60 cells were seeded into 48 well plates, YG-labeled microspheres and polysaccharides were added and mixed using a plate shaker at 1100 rpm for 30 s, and then the mixture was incubated overnight at 37 degrees C in 5% CO2. The cells were fixed with 2% formaldehyde and resuspended in phosphate-buffered saline. The rate of phagocytosis was measured with a flow cytometer. VD3-differentiated cells but not non- and PMA differentiated cells resulted in an elevation of phagocytic activity by various immune-enhancing polysaccharides in foods. PMID- 17338547 TI - Analytical performances of aptamer-based sensing for thrombin detection. AB - Aptamer-based assays represent a modern and attractive approach in bioanalytical chemistry. The DNA thrombin aptamer has been extensively investigated, and the coupling of this aptamer to different transduction principles has demonstrated the wide applicability of aptamers as bioreceptors in bioanalytical assays. The goal of this work was to critically evaluate all the parameters that can influence the sensor performances by using the thrombin aptamer immobilized onto piezoelectric quartz crystals. The optimization of the immobilization and the binding protocol was of paramount importance, and improvements in analytical performances could be obtained by optimizing simple steps in immobilization and assay conditions. Moreover, the work demonstrated the possibility of using aptamer-based sensors in complex matrixes, opening the possibility of a real application to diagnostics or medical investigation. PMID- 17338548 TI - Granular tau oligomers as intermediates of tau filaments. AB - Neurofibrillary tangles (NFTs) are pathological hallmarks of several neurodegenerative disorders, including Alzheimer's disease (AD). NFTs are composed of microtubule-binding protein tau, which assembles to form paired helical filaments (PHFs) and straight filaments. Here we show by atomic force microscopy that AD brain tissue and in vitro tau form granular and fibrillar tau aggregates. CD spectral analysis and immunostaining with conformation-dependent antibodies indicated that tau may undergo conformational changes during fibril formation. Enriched granules generated filaments, suggesting that granular tau aggregates may be an intermediate form of tau fibrils. The amount of granular tau aggregates was elevated in prefrontal cortex of Braak stage I cases compared to that of Braak stage 0 cases, suggesting that granular tau aggregation precedes PHF formation. Thus, granular tau aggregates may be a relevant marker for the early diagnosis of tauopathy. Reducing the level of these aggregates may be a promising therapy for tauopathies and for promoting healthy brain aging. PMID- 17338549 TI - Reconciling the solution and X-ray structures of the villin headpiece helical subdomain: molecular dynamics simulations and double mutant cycles reveal a stabilizing cation-pi interaction. AB - The 36-residue helical subdomain of the villin headpiece, HP36, is one of the smallest cooperatively folded proteins, folding on the microsecond time scale. The domain is an extraordinarily popular model system for both experimental and computational studies of protein folding. The structure of HP36 has been determined using X-ray crystallography and NMR spectroscopy, with the resulting structures exhibiting differences in helix packing, van der Waals contacts, and hydrogen bonding. It is important to determine the solution structure of HP36 with as much accuracy as possible since this structure is widely used as a reference for simulations and experiments. We complement the existing data by using all-atom molecular dynamics simulations with explicit solvent to evaluate which of the experimental models is the better representation of HP36 in solution. After simulation for 50 ns initiated with the NMR structure, we observed that the protein spontaneously adopts structures with a backbone conformation, core packing, and C-capping motif on the third helix that are more consistent with the crystal structure. We also examined hydrogen bonding and side chain packing interactions between D44 and R55 and between F47 and R55, respectively, which were observed in the crystal structure but not in the NMR based solution structure. Simulations showed large fluctuations in the distance between D44 and R55, while the distance between F47 and R55 remained stable, suggesting the formation of a cation-pi interaction between those residues. Experimental double mutant cycles confirmed that the F47-R55 pair has a larger energetic coupling than the D44-R55 interaction. Overall, these combined experimental and computational studies show that the X-ray crystal structure is the better reference structure for HP36 in solution at neutral pH. Our analysis also shows how detailed molecular dynamics simulations combined with experimental validation can help bridge the gap between NMR and crystallographic methods. PMID- 17338550 TI - Differentiation of secreted and membrane-type matrix metalloproteinase activities based on substitutions and interruptions of triple-helical sequences. AB - The turnover of the collagen triple-helical structure (collagenolysis) is a tightly regulated process in normal physiology and has been ascribed to a small number of proteases. Several members of the matrix metalloproteinase (MMPs) family possess collagenolytic activity, and the mechanisms by which these enzymes process triple helices are beginning to be unraveled. The present study has utilized two triple-helical sequences to compare the cleavage-site specificities of 10 MMPs. One substrate featured a continuous Gly-Xxx-Yyy sequence (Pro-Leu-Gly approximately Met-Arg-Gly), while the other incorporated an interruption in the Gly-Xxx-Yyy repeat (Pro-Val-Asn approximately Phe-Arg-Gly). Both sequences were selectively cleaved by MMP-13 while in linear form, but neither proved to be selective within a triple helix. This suggests that the conformational presentation of substrate sequences to a MMP active site is critical for enzyme specificity, in that activities differ when sequences are presented from an unwound triple helix versus an independent single strand. Differences in specificity between secreted and membrane-type (MT) MMPs were also observed for both sequences, where MMP-2 and MT-MMPs showed an ability to hydrolyze a triple helix at an additional site (Gly-Gln bond). Interruption of the triple helix had different effects on secreted MMPs and MT-MMPs, because MT-MMPs could not hydrolyze the Asn-Phe bond but instead cleaved the triple helix closer to the C terminus at a Gly-Gln bond. It is possible that MT-MMPs have a requirement for Gly in the P1 subsite to be able to efficiently process a triple-helical molecule. Analysis of individual kinetic parameters and activation energies indicated different substrate preferences within secreted MMPs, because MMP-13 preferred the interrupted sequence, while MMP-8 showed little discrimination between non-interrupted and interrupted triple helices. On the basis of the present and prior studies, we can assign unique triple-helical peptidase behaviors to the collagenolytic MMPs. Such differences may be significant for understanding MMP mechanisms of action and aid in the development of selective MMP inhibitors. PMID- 17338551 TI - Kinetic manifestation of processivity during multiple methylations catalyzed by SET domain protein methyltransferases. AB - Processive versus distributive methyl group transfer was assessed for pea Rubisco large subunit methyltransferase, a SET domain protein lysine methyltransferase catalyzing the formation of trimethyllysine-14 in the large subunit of Rubisco. Catalytically competent complexes between an immobilized form of des(methyl) Rubisco and Rubisco large subunit methyltransferase were used to demonstrate enzyme release that was co-incident with and dependent on formation of trimethyllysine. Catalytic rate constants determined for formation of trimethyllysine were considerably lower ( approximately 10-fold) than rate constants determined for total radiolabel incorporation from [3H-methyl]-S adenosylmethionine. Double-reciprocal velocity plots under catalytic conditions favoring monomethyllysine indicated a random or ordered reaction mechanism, while conditions favoring trimethyllysine suggested a hybrid ping-pong mechanism. These results were compared with double-reciprocal velocity plots and product analyses obtained for HsSET7/9 (a monomethyltransferase) and SpCLR4 (a dimethyltransferase) and suggest a predictive ability of double-reciprocal velocity plots for single versus multiple methyl group transfers by SET domain protein lysine methyltransferases. A model is proposed for SET domain protein lysine methyltransferases in which initial binding of polypeptide substrate and S adenosylmethionine is random, with polypeptide binding followed by deprotonation of the epsilon-amine of the target lysyl residue and subsequent methylation. Following methyl group transfer, S-adenosylhomocysteine and monomethylated polypeptide dissociate from monomethyltransferases, but di- and trimethyltransferases begin a successive and catalytically obligatory deprotonation of enzyme-bound methylated lysyl intermediates, which along with binding and release of S-adenosylmethionine and S-adenosylhomocysteine is manifested as a hybrid ping-pong-like reaction mechanism. PMID- 17338552 TI - A fluorescence spectroscopy study on the interactions of the TAT-PTD peptide with model lipid membranes. AB - Protein-transduction domains (PTDs) have been shown to translocate into and through the living cells in a rapid manner by an as yet unknown mechanism. Regardless of the mechanism of translocation, the first necessary step must be binding of the PTD peptide to the surface of the lipid membrane. We used fluorescence spectroscopy to study the interaction between PTD of the HIV-1 Tat protein (TAT-PTD; residues 47-60 of Tat, fluorescently labeled with tryptophan) and the lipid bilayer labeled with various fluorescence membrane probes. The TAT PTD tryptophan exhibited a decrease in fluorescence intensity and an increase in anisotropy upon interaction with lipid bilayers. The fluorescence changes were linearly proportional to the density of negative charge in the membrane. Kinetic analysis of the interaction showed two apparent dissociation constants. The value of one dissociation constant (Kd1 = 2.6 +/- 0.6 microM), which accounted for 24% of the interaction, was found to be independent of the negative charge density, suggesting its nonelectrostatic nature. The value of the second dissociation constant (Kd2), which accounted for 76% of the interaction, decreased linearly from 610 +/- 150 to 130 +/- 30 microM with an increase in negative charge density from 0 to 25 mol %, suggesting this interaction is electrostatic in nature. Even though the binding was predominantly electrostatic, it could not be reversed by high salt, indicating the presence of a second, irreversible, step in the interaction with lipid. When TAT-PTD was bound to lipid vesicles labeled with 1 (4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), fluorescence resonance energy transfer between the tryptophan and the probe occurred at a distance of 3.4 nm. No change in fluorescence anisotropy of either TMA-DPH or DPH was observed upon the interaction with TAT-PTD, indicating no significant disruption or perturbation of the lipid bilayer by the peptide. TAT-PTD did not cause dissipation of membrane potential (165 mV, negative inside). Inclusion of 3% pyrene-labeled phosphatidylglycerol (pyrene-PG) in the membrane revealed that TAT-PTD preferentially bound to the membrane in the liquid state. We conclude that membrane fluidity is an important physicochemical parameter, which may regulate binding of TAT-PTD to the membrane. PMID- 17338554 TI - Surface reactivity of pulsed-plasma polymerized pentafluorophenyl methacrylate (PFM) toward amines and proteins in solution. AB - Pulsed-plasma polymerization has been used to deposit ultrathin layers of pentafluorophenyl methacrylate by using low duty cycles and low power input. The monomer structure can be retained such that the chemical reactivity of the active ester group could be studied using the reaction with a simple amine. The film properties in aqueous phosphate buffer have been investigated using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and real time surface plasmon resonance spectroscopy. The films react readily with diaminohexane and immunoglobulin (IgG), yet the reactivity shows a dependence on the extent of hydrolysis of the ester group. PMID- 17338553 TI - Facilitation of quantal release induced by a D1-like receptor on bovine chromaffin cells. AB - Dopaminergic receptors are found on bovine adrenal chromaffin cells and have been implicated in the facilitation of an inward calcium current [Artalejo et al., (1990) Nature 348, 239-242] that could enhance release. However, previous studies using incubations of long duration (minutes) with dopaminergic receptor antagonists have found instead an inhibition of catecholamine release. In this work we used brief (subsecond) chemical depolarizing stimuli to reexamine the role of dopaminergic receptors on exocytosis from bovine adrenal chromaffin cells. Responses to consecutive depolarizing stimuli were compared using amperometry to monitor vesicular release events and intracellular fura-2 to examine Ca2+ dynamics within individual cells. Restoration of intracellular Ca2+ levels to their initial values following exposure to 60 mM K+ was found to be prolonged unless the exposure was brief (0.5 s) and the cells were maintained at 37 degrees C. However, with these optimum conditions, a second stimulation evoked more exocytotic events than the first. This effect was blocked by SCH-23390, a D1 antagonist, in a dose dependent fashion, but not by raclopride, a D2 antagonist. The D1 agonist, SKF-38393, enhanced the number of exocytotic events as did prior exposure of the cell to epinephrine. Taken together, the data indicate that released catecholamines can enhance their own release by interaction with a D1 like receptor on bovine adrenal chromaffin cells. PMID- 17338555 TI - Forces between surfaces across nanoparticle solutions: role of size, shape, and concentration. AB - Using a surface force apparatus, we have measured the normal forces between mica surfaces across various types of nanoparticles consisting of ZnS cores coated with a monolayer of physisorbed surfactant, dispersed in organic solvents. We focused on the effects of nanoparticle size, shape, and concentration on the force-distance profiles. Forces were exponentially repulsive when the surfactant layers were strongly bound to the nanoparticles and were roughly linear when there was adhesion between the nanoparticle cores, i.e., when the surfactant layers detached from the nanoparticles. In both cases, the range and magnitude of the forces were dependent upon the particle size, shape, and solution concentration. Fine details in the otherwise smooth force-distance profiles indicate specific effects due to particle chemistry and geometry and the existence of first-order disorder-order phase transitions upon confinement. Small amounts of water in the (hydrophobic) organic solvents had dramatic effects on the measured forces. Understanding and controlling the effects of particle shape, size, and concentration and the presence of water (or other surface-active solutes) on particle-particle and particle-surface interactions are important for the processing of nanoparticles into ordered superstructured materials. PMID- 17338556 TI - Lecithin organogels used as bioactive compounds carriers. A microdomain properties investigation. AB - Organogels were obtained by adding small amounts of water to a solution of lecithin in organic solvents. Either isooctane or isopropyl palmitate and isopropyl myristate were used as the continuous organic phase of the gels. EPR spectroscopy using both DSA membrane-sensitive and lipophilic spin probes was applied to define the dynamic structure of the surfactant monolayer and the continuous oil phase of lecithin organogels. It was found that by increasing the water quantity, an increase of the polar head area per lecithin molecule was induced, and as a consequence the total interface expanded. It was found that the use of esters as organic solvents induced a decrease of the size of the dispersed structures. The interconnection of the aqueous microdomains and their dynamics were monitored by both static and time-resolved fluorescence quenching spectroscopy using Ru(bipy)32+ as fluorophore and Fe(CN)63- as quencher. It was found that the rates of inter- and/or intra-micellar exchange of water molecules were very slow because they appeared quite immobilized close to the lecithin polar heads. According to the results of the dynamic studies, appropriate organogels were formulated and used to incorporate model bioactive compounds with medicinal or cosmetic interest such as caffeine and theophylline. When these systems were tested for trans-membrane diffusion, they showed a 24 h permeation of 20% and 35%, respectively. PMID- 17338557 TI - Probing the permeability of polyelectrolyte multilayer capsules via a molecular beacon approach. AB - Application of polyelectrolyte multilayer (PEM) capsules as vehicles for the controlled delivery of substances, such as drugs, genes, pesticides, cosmetics, and foodstuffs, requires a sound understanding of the permeability of the capsules. We report the results of a detailed investigation into probing capsule permeability via a molecular beacon (MB) approach. This method involves preparing MB-functionalized bimodal mesoporous silica (BMSMB) particles, encapsulating the BMSMB particles within the PEM film to be probed, and then incubating the encapsulated BMSMB particles with DNA target sequences of different lengths. Permeation of the DNA targets through the capsule shell causes the immobilized MBs to open due to hybridization of the DNA targets with the complementary loop region of the MBs, resulting in an increase in the MB fluorescence. The assay conditions (BMSMB particle concentration, MB loading within the BMS particles, DNA target concentration, DNA target size, pH, sodium chloride concentration) where the MB-DNA sensing process is effective were first examined. The permeability of DNA through poly(sodium 4-styrenesulfonate) (PSS)/poly(allylamine hydrochloride) (PAH) multilayer films, with and without a poly(ethyleneimine) (PEI) precursor layer, was then investigated. The permeation of the DNA targets decreases considerably as the thickness of the PEM film encapsulating the BMSMB particles increases. Furthermore, the presence of a PEI precursor layer gives rise to less permeable PSS/PAH multilayers. The diffusion coefficients calculated for the DNA targets through the PEM capsules range from 10-19 to 10-18 m2 s-1. This investigation demonstrates that the MB approach to measuring permeability is an important new tool for the characterization of PEM capsules and is expected to be applicable for probing the permeability of other systems, such as membranes, liposomes, and emulsions. PMID- 17338558 TI - Proteomic analysis of the resistance to aplidin in human cancer cells. AB - Aplidin (plitidepsin) is an antitumoral agent that induces apoptosis via Rac1-JNK activation. A proteomic approach using 2D-DIGE technology found 52 cytosolic and 39 membrane proteins differentially expressed in wild-type and Aplidin-resistant HeLa cells, of which 39 and 27 were identified by MALDI-TOF mass spectrometry and database interrogation. A number of proteins involved in apoptosis pathways were found to be deregulated. Alterations in Rab geranylgeranyltransferase, protein disulfide isomerase (PDI), cystathionine gamma-lyase, ezrin, and cyclophilin A (CypA) were confirmed by immunoblotting. Moreover, the role of PDI and CypA in Aplidin resistance was functionally confirmed by using the inhibitor bacitracin and overexpression, respectively. These deregulated proteins are candidates to mediate, at least partially, Aplidin action and might provide a route to the cells to escape the induction of apoptosis by this drug. PMID- 17338559 TI - Modeling protein-protein complexes involved in the cytochrome C oxidase copper delivery pathway. AB - Proper assembly and function of cytochrome c oxidase, which catalyzes the reduction of O2 and generates the proton gradient driving ATP synthesis, depend on correct copper delivery and incorporation. Structural details about the protein-protein complexes involved in this process are still missing. We describe here models of four complexes along this pathway obtained by combining bioinformatics interface predictions with information-driven docking and discuss their relevance with respect to known and pathogenic mutations. PMID- 17338560 TI - Formation of a lamellar compound by reaction of acrylic acid crystallosolvated in highly crystalline beta-chitin. AB - A lamellar compound resulted from reaction of acrylic acid inside crystalline beta-chitin and the structure was investigated. Beta-chitin acts like a layered crystal, having stacked molecular sheets composed of parallel chains bound in one direction by intermolecular amide hydrogen bonding. Small guest molecules can be inserted between the molecular sheets, and a crystallosolvate can be formed. By immersion of beta-chitin in acrylic acid, a crystallosolvate was formed, which was then changed into the more stable lamellar compound by heat treatment at 105 degrees C. NMR measurement and IR spectroscopy showed that during the heat treatment there was a reaction between acrylic acid and the beta-chitin molecular sheet, but the sheet structure was maintained. By IR with deuteration, it was shown that the accessibility of solvents to this lamellar compound was greater than that for the initial beta-chitin. The lamellar compound is considered a kind of "pillared" structure related to the lamellar crystal. PMID- 17338561 TI - Monohydroxylated poly(3-hydroxyoctanoate) oligomers and its functionalized derivatives used as macroinitiators in the synthesis of degradable diblock copolyesters. AB - The presence of a hydroxyl group at the end of poly(3-hydroxyoctanoate) oligomers, noted PHO oligomers, is required to prepare diblock copolymers with improved properties by ring-opening polymerization of cyclic monomer as epsilon caprolactone. Several chemical methods such as basic hydrolysis, acid-catalyzed reaction with APTS, and methanolysis were used to prepare well-defined low molar masses PHO oligomers. The methanolysis reaction was allowed to proceed for 10-60 min to produce PHO oligomers with Mn values ranging from 20,000 to 800 g mol-1 with low polydispersity index. Detailed analysis of the MALDI-TOF mass spectra of the obtained oligomers has revealed the presence of linear structures bearing methyl ester on one side and hydroxyl end group on the other side. The same procedure was applied to poly(3-hydroxyoctanoate-co-3-hydroxyundecenoate), PHOU, a poly(3-hydroxyalkanoate) containing unsaturated units in its side chains. These oligomers were further used to initiate the polymerization of epsilon caprolactone by varying the PHO (or PHOU) and PCL lengths. By copolymerization with epsilon-caprolactone, the properties of PHO or PHOU have been improved. The crystallinity of the obtained copolymers was modified by controlling the length of the two different blocks. The unsaturations in the side chains of the PHOU block were oxidized in acid carboxylic functions to obtain a novel artificial biopolyester. Moreover, degradation was followed to study the influence of carboxylic groups on the hydrolysis of the copolymers. PMID- 17338562 TI - Chemical and physical properties of sulfated silk fabrics. AB - Silk fabrics were treated with chlorosulphonic acid in pyridine for different times. The amount of sulfur bound to silk increased during the first 2 h of reaction and then reached a plateau. The amino acidic pattern of sulfated silk remained essentially unchanged for short reaction times (< or =2 h). Longer reaction times resulted in drastic changes in the concentration of Asp, Glu, and Tyr. Surface morphology and texture of silk fabrics changed upon sulfation. Warp and weft yarns became progressively thinner, and deposits of foreign material appeared on the fiber surface. Changes were more evident at longer reaction times (> or =2 h). Spectroscopic analyses performed by FT-IR and FT-Raman showed the appearance of new bands attributable to various vibrations of sulfated groups. The IR bands at 1049 and 1014 cm-1, due to organic sulfate salts, were particularly intense. Bands assigned to alkyl sulfates and sulfonamides appeared in the 1300-1180 cm-1 range. Organic covalent sulfates displayed a weak but distinct IR band at 1385 cm-1. Both IR and Raman spectra revealed that silk fibroin mainly bound sulfates through the hydroxyl groups of Ser and Tyr, while involvement of amines could not be proved. Changes observed in the amide I and II range indicated an increase of the degree of molecular disorder of sulfated silk. Accordingly, the I850/I830 intensity ratio between the two Tyr bands at 850-830 cm-1 increased from 1.41 to 1.52, indicating a more exposed state of Tyr residues in sulfated silk. TGA, DSC, and TG analyses showed that sulfated silk attained a higher thermal stability. A thermal transition attributable to sulfated silk fibroin fractions appeared at about 260 degrees C in the DSC thermograms. PMID- 17338563 TI - Miscibility of bioerodible polyphosphazene/poly(lactide-co-glycolide) blends. AB - We have previously demonstrated the feasibility of blending bioerodible polyphosphazenes with poly(lactide-co-glycolide) (PLGA) to form versatile polymeric materials with altered bioerosion properties. These studies demonstrated the effective neutralization of the acidic degradation products of PLGA by the polyphosphazene hydrolysis products. In the present study, five new polymers of dipeptide polyphosphazenes poly[(ethyl glycinato)x(glycyl-ethyl glycinato)yphosphazene] and novel blends of these polyphosphazenes with poly(lactide-co-glycolide) (PLGA) were synthesized and fabricated. The miscibility was analyzed using differential scanning calorimetry and scanning electron microscopy. Hydrogen bonding within the blends was assessed by attenuated total reflectance infrared spectroscopy. The phosphazene component of the blend contained varying ratios of the glycyl-glycine ethyl ester to the glycine ethyl ester. Poly[(ethyl glycinato)0.5(glycine ethyl glycinato)1.5phosphazene formed completely miscible blends with PLGA (50:50) and PLGA (85:15). This is ascribed to the multiple hydrogen-bonding sites within the side groups of the polyphosphazene. The components of the blend act as plasticizers for each other because a glass transition temperature for each blend was detected at a lower temperature than for each individual polymer. A hydrolysis study showed that unblended solid poly[(ethyl glycinato)0.5(glycyl ethyl glycinato)1.5phosphazene] hydrolyzed in less than 1 week. However, the blends degraded at a slower rate than both parent polymers. This is attributed to the buffering capacity of the polyphosphazene hydrolysis products, which increases the pH of the degradation media from 2.5 to 4, thereby slowing the degradation rate of PLGA. PMID- 17338564 TI - Sulfated triterpene derivatives from Fagonia arabica. AB - Two new sulfated triterpenes (1, 6) and four new sulfated triterpene glycosides (2-5) have been isolated from the aerial parts of Fagonia arabica. Their structures were established by spectroscopic data analysis. Compounds 1/2 and 3/4 are sulfated derivatives of the rare sapogenins 3beta,27-dihydroxyolean-12-en-28 oic acid and 3beta,27-dihydroxyurs-12-en-28-oic acid, respectively. Compound 5 is an unusual disulfated oleanene derivative characterized by the occurrence of a 13,18-double bond, while compound 6 is the first reported naturally occurring saturated and sulfated pentacyclic triterpene of the taraxastane series with a C 20,28 lactone unit. PMID- 17338565 TI - Kaurane diterpenoids from Isodon excisus inhibit LPS-induced NF-kappaB activation and NO production in macrophage RAW264.7 cells. AB - As part of an ongoing search for plant-derived compounds that inhibit the activation of NF-kappaB, the methanol extract of the aerial parts of Isodon excisus was found to have significant inhibitory effects on the activation of NF kappaB in murine macrophage RAW264.7 cells. Bioactivity-guided isolation of the extract yielded five new diterpenoids, excisusin A-E (1-5), along with seven known compounds, inflexarabdonin I (6), inflexarabdonin G (7), inflexin (8), inflexanin A (9), inflexanin B (10), inflexinol (11), and inflexarabdonin A (12). The structures were determined by analysis of the spectroscopic data including 2D NMR. All of the isolates were evaluated for their inhibitory effects on LPS induced NF-kappaB activation and nitric oxide production in RAW264.7 cells. PMID- 17338566 TI - Synthesis of the isolable biradicals *(CH3B)11C-C triple bond C-C(BCH3)11* and trans-*(CH3B)11C-CH=CH-C(BCH3)11*. AB - A synthesis of ethene and ethyne derivatives carrying the anionic -C(BCH3)11- substituent on one or both carbon atoms is described. Two-electron oxidation of the dianions yielded the stable and isolable electroneutral title biradicals. PMID- 17338567 TI - CuCl-induced formation and migration of isoindazolyl carbenoids. AB - Two azo-ene-butadiyne conjugated systems undergo CuCl-mediated cyclization to afford isoindazolyl carbenoids that could be trapped with 2,3-dimethyl-2-butene as [2+1] cycloaddition products. X-ray structure analysis of the resultant cyclopropanes showed that formal migration to the distal carbenoid isomer and subsequent trapping had occurred. The possible CuCl-induced cyclization/migration pathways were explored using density functional theory, which indicated that the reaction most likely occurred via coordination of CuCl to the distal alkyne bond. PMID- 17338568 TI - Regioisomerically controlled self-aggregation of zinc 3-hydroxymethyl-13-formyl chlorin/porphyrin and their 3,13-inverted pigments. AB - Zinc 3-hydroxymethyl-13-formyl-chlorin, 1, and its 3,13-inverted (3-formyl-13 hydroxymethyl) regioisomer, 2, and their corresponding 17,18-dehydrogenated porphyrins, 3 and 4, were synthesized for models of natural bacteriochlorophylls c/d/e possessing 3(1)-OH and 13-C=O groups which self-aggregate in main light harvesting antenna systems of green photosynthetic bacteria. Zinc chlorins 1 and 2 were monomers in neat THF and gave an obvious difference in their visible absorption spectra, indicating that sole inversion of the 3- and 13-substituents in a chlorin chromophore controlled their optical properties. In an aqueous Triton X-100 solution (a nonionic surfactant), zinc 3(1)-OH-13-CHO-chlorin 1 and porphyrin 3 self-aggregated as do natural bacteriochlorophylls, while zinc 3-CHO 13(1)-OH chlorin 2 and porphyrin 4 (the 3,13-inverted regioisomers of 1 and 3) hardly formed such large oligomers, showing that the inversion of the peripheral 3,13-substituents made their oligomerization unfavorable. FT-IR spectra of aggregated 1-4 in the solid film and their molecular modeling calculations suggested that the 17(2)-C=O moiety in inverted 2/4 interacted with its own 13(1) OH group to disturb further aggregation. PMID- 17338569 TI - Enantioselective cyanosilylation of alpha,alpha-dialkoxy ketones catalyzed by proline-derived in-situ-prepared N-oxide as bifunctional organocatalyst. AB - Bifunctional N,N'-dioxide catalysts have been developed for highly enantioselective cyanosilylation of alpha,alpha-dialkoxy ketones. This process, catalyzed by in-situ-prepared proline-derived N,N'-dioxide 2b, produced the corresponding cyanohydrin trimethylsilyl ethers in excellent yields (up to 99%) with high enantioselectivities (up to 93% ee). A reasonable mechanism was proposed according to the observation of the linear effect, 1H NMR spectra, isolated cyanohydrin, and the roles of the NH and N-oxide moieties of the catalyst. PMID- 17338570 TI - O-sialylation with N-acetyl-5-n,4-o-carbonyl-protected thiosialoside donors in dichloromethane: facile and selective cleavage of the oxazolidinone ring. AB - An N-acetyl-5-N,4-O-carbonyl-protected thiosialoside donor, the structure of which has been defined through X-ray crystallography, was prepared and tested in couplings to a wide range of acceptors. This donor gives excellent yields and alpha-selectivities in linking with various primary alkyl and carbohydrate acceptors under the N-iodosuccinimide and trifluoromethanesulfonic acid in situ activation method at -40 degrees C in dichloromethane. The favorable affect of the oxazolidinone substructure for alpha-sialylation is illustrated by a comparison study with a N,N-diacetylsialyl donor, which exhibited inferior yields and alpha-selectivities. The sialylation selectivity is independent of the anomeric configuration of the donor, but is highly related to the reaction temperature under the NIS/TfOH activation method. In contrast to the NIS/TfOH method, the Ph2SO/Tf2O promotion gives beta-selective couplings in dichloromethane. The oxazolidinone of the N-acetyl-5-N,4-O-carbonyl protected sialosides, both alpha- and beta-anomers, could be cleaved cleanly by treatment with sodium methoxide under mild conditions without removal of the acetamide. PMID- 17338571 TI - Enthalpy (DeltaH) and entropy (DeltaS) for pi-stacking interactions in near sandwich configurations: relative importance of electrostatic, dispersive, and charge-transfer effects. AB - Interactions between two aromatic rings with various substituents in a near sandwich configuration have been quantitatively studied by using the triptycene derived molecular models. This model system allows a stacking arrangement of two arenes to assume a near-perfect face-to-face configuration in its ground state conformation. Comparing to our previous study of the parallel displaced configuration, repulsive interactions are predominant for most arenes currently studied. However, if one arene is strongly electron deficient (Ar2=pentafluorobenzoate), attractive interactions were observed regardless of the character of the other arene (Ar1). For stacking interactions between Me2NC6H4 and C6F5CO groups, a DeltaH of -1.84+/-0.2 kcal/mol and a DeltaS of 2.9+/-0.8 cal/(mol.K) were determined. The general trend in the attractive stacking interaction toward a pentafluorobenzoate is Me2NC6H4>Me3C6H2>Me2C6H3>MeC6H4>MeOC6H4>C6H5>O2NC6H4. The observed trend is consistent with a donor-acceptor relationship and the acceptor is a C6F5CO group. PMID- 17338572 TI - An intramolecular aza-[3+3] annulation approach to azaphenalene alkaloids. Total synthesis of myrrhine. AB - A detailed account on the stereoselective total syntheses of azaphenalene alkaloids via an intramolecular aza-[3+3] annulation strategy is described here. All five members of the Coccinellidae family of defensive alkaloids were prepared from the same common intermediate, which was derived from a stereoselective aza [3+3] annulation reaction. PMID- 17338573 TI - De novo approach to 2-deoxy-beta-glycosides: asymmetric syntheses of digoxose and digitoxin. AB - A highly enantioselective and straightforward route to trisaccharide natural products digoxose and digitoxin has been developed. Key to this approach is the iterative application of the palladium-catalyzed glycosylation reaction, reductive 1,3-transposition, diastereoselective dihydroxylation, and regioselective protection. The first total synthesis of natural product digoxose was accomplished in 19 total steps from achiral 2-acylfuran, and digitoxin was fashioned in 15 steps starting from digitoxigenin 2 and pyranone 8beta. This flexible synthetic strategy also allows for the preparation of mono- and disaccharide analogues of digoxose and digitoxin. PMID- 17338574 TI - Determination of the absolute configurations of natural products via density functional theory calculations of vibrational circular dichroism, electronic circular dichroism and optical rotation: the schizozygane alkaloid schizozygine. AB - The development of density functional theory (DFT) methods for the calculation of vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and transparent spectral region optical rotation (OR) has revolutionized the determination of the absolute configurations (ACs) of chiral molecules using these chiroptical properties. We report the first concerted application of DFT calculations of VCD, ECD, and OR to the determination of the AC of a natural product whose AC was previously undetermined. The natural product is the alkaloid schizozygine, isolated from Schizozygia caffaeoides. Comparison of DFT calculations of the VCD, ECD, and OR of schizozygine to experimental data leads, for each chiroptical technique, to the AC 2R,7S,20S,21S for the naturally occurring (+)-schizozygine. Three other alkaloids, schizogaline, schizogamine, and 6,7-dehydro-19beta-hydroxyschizozygine, have also been isolated from S. caffaeoides and shown to have structures closely related to schizozygine. Assuming a common biosynthetic pathway, their ACs are defined by that of schizozygine. PMID- 17338575 TI - Synthesis of some members of the hydroxylated phenanthridone subclass of the Amaryllidaceae alkaloid family. AB - The total synthesis of several members of the hydroxylated phenanthridone subclass of the Amaryllidaceae alkaloid family has been carried out. (+/-) Lycoricidine and (+/-)-7-deoxypancratistatin were assembled through a one-pot Stille/intramolecular Diels-Alder cycloaddition cascade to construct the core skeleton. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by a deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone on further heating at 160 degrees C. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered vinyl group oriented exo with respect to the oxygen bridge. The resulting cycloadduct was used for the stereocontrolled installation of the remaining functionality present in the C-ring of the target molecules. Key features of the synthetic strategy include (1) a lithium hydroxide induced tandem hydrolysis/decarboxylation/elimination sequence to introduce the required pi-bond in the C-ring of (+/-)-lycoricidine, and (2) conversion of the initially formed Diels-Alder adduct into an aldehyde intermediate which then undergoes a stereospecific decarbonylation reaction mediated by Wilkinson's catalyst to set the trans-B-C ring junction of (+/-)-7-deoxypancratistatin. PMID- 17338576 TI - Sulfoxide-induced stereoselection in [1,5]-sigmatropic hydrogen shifts of vinylallenes. A computational study. AB - The sulfoxide-induced preference for a migrating trajectory in the vinylallene [1,5]-H sigmatropic shift (resulting in stereodefined trienes in the conceptual equivalent of torquoselectivity in electrocyclizations), originally reported by Okamura, has been computationally studied at the B3LYP/6-311++G(3df,2p)//B3LYP/6 31++G(d,p) level. The face selectivity this group induces in the [1,5]-H shift is enhanced by bulky geminal substituents and is not reproduced by any of the other (more than 20) substituents tested. Analysis of transition-state geometries or charges and evaluation of steric effects did not show any correlation with the preferences. The origin of this selectivity is thought to lie in a secondary orbital interaction (SOI) involving the termini of the pericyclic array and the sulfinyl group which is only observed for this substituent. This secondary orbital interaction, arising from the favorable energies of the orbitals involved, is enhanced in the transition structure due to a better orbital overlap (piC2-C3-->sigma*C1-S), which correlates with a piC2-C3-->sigma*C6-H SOI, which is more important in the transition structure, that weakens the C-H bond, thus lowering the energy of the corresponding transition structure. PMID- 17338577 TI - Interaction of beta-lactam carbenes with aryl isonitriles: an unprecedented rearrangement of 2-azetidinonylidene indoles to delta-carbolinones. AB - The reaction of beta-lactam carbenes with aryl isonitriles proceeded in a novel [2 + 2] fashion to give high yields of 2-azetidinonylidene indoles 4, which underwent an unprecedented rearrangement to furnish 4-arylimino-delta-carbolin-2 ones 5 in almost quantitative yields. Acid catalyzed rearrangement and the subsequent hydrolysis of 2-azetidinonylidene indoles 4 produced two types of delta-carbolin-2,4-diones 10 and 11, respectively, in good to excellent yields. The photophysical study showed that both delta-carbolin-2,4-diones 10 and 11 are highly fluorescent with the fluorescent quantum yields being up to 0.43. PMID- 17338591 TI - The National Institute for Health and Clinical Excellence (NICE) and drug treatment for Alzheimer's disease. AB - Britain's National Institute for Health and Clinical Excellence (NICE) has recently issued guidance that restricts the use of cholinesterase inhibitors and memantine for the treatment of Alzheimer's disease in the National Health Service. This stance contains lessons for designers of trials, drug regulators, health economists and those developing clinical guidelines for dementia care. The debates that took place around and within NICE were about identifying the benefits of these medicines and the beneficiaries, clarifying the costs of the medication and whom bears them, the methods of weighing benefit against cost, and the consequences of using different approaches to cost-benefit analysis. This article discusses each of these themes and outlines the changes in research and clinical practice and policy making that might flow from NICE's decisions on medication use. Outcome measures that capture changes in dementia syndromes need further development. Cost-benefit analysis needs refinement with better tools than quality-adjusted life-years, and the policy implications of restricting treatments in a progressive neurodegenerative disorder need more careful consideration. PMID- 17338592 TI - Perioperative pain management. AB - The under-treatment of postoperative pain has been recognised to delay patient recovery and discharge from hospital. Despite recognition of the importance of effective pain control, up to 70% of patients still complain of moderate to severe pain postoperatively. The mechanistic approach to pain management, based on current understanding of the peripheral and central mechanisms involved in nociceptive transmission, provides newer options for clinicians to manage pain effectively. In this article we review the rationale for a multimodal approach with combinations of analgesics from different classes and different sites of analgesic administration. The pharmacological options of commonly used analgesics, such as opioids, NSAIDs, paracetamol, tramadol and other non-opioid analgesics, and their combinations is discussed. These analgesics have been shown to provide effective pain relief and their combinations demonstrate a reduction in opioid consumption. The basis for using non-opioid analgesic adjuvants is to reduce opioid consumption and consequently alleviate opioid-related adverse effects. We review the evidence on the opioid-sparing effect of ketamine, clonidine, gabapentin and other novel analgesics in perioperative pain management. Most available data support the addition of these adjuvants to routine analgesic techniques to reduce the need for opioids and improve quality of analgesia by their synergistic effect. Local anaesthetic infiltration, epidural and other regional techniques are also used successfully to enhance perioperative analgesia after a variety of surgical procedures. The use of continuous perineural techniques that offer prolonged analgesia with local anaesthetic infusion has been extended to the care of patients beyond hospital discharge. The use of nonpharmacological options such as acupuncture, relaxation, music therapy, hypnosis and transcutaneous nerve stimulation as adjuvants to conventional analgesia should be considered and incorporated to achieve an effective and successful perioperative pain management regimen. PMID- 17338594 TI - Psychostimulants in the treatment of depression : a review of the evidence. AB - Psychostimulants have euphoric and alerting properties that suggest their usefulness in treating depressive disorders; however, problems with tolerance and dependence with some drugs militate against their widespread therapeutic use where more acceptable licensed alternatives are available. The introduction of modafinil, a stimulant not associated with tolerance and dependence, has re awakened interest in psychostimulants as antidepressants. The available literature, while containing somewhat inconsistent data of rather poor quality, does suggest that psychostimulants have useful antidepressant properties and are usually well tolerated. They may be useful as adjuncts to standard antidepressants in refractory depression, but have particular utility in conditions where a prompt therapeutic effect is desired and where tolerance and dependence are less of a concern. Such conditions include the treatment of depression in terminal illness and in extreme old age.Psychostimulants, although now largely discarded as treatment options for depression, deserve careful consideration as potential therapeutic agents in specific patient subgroups. PMID- 17338593 TI - Pharmacotherapy of dual substance abuse and dependence. AB - The US FDA has approved a limited number of treatments for alcohol, nicotine and opioid dependence; however, no treatments for other abused drugs such as marijuana, cocaine or methamphetamine are approved. This review focuses on research into drug pharmacotherapies, particularly single-drug therapies, for substance abuse and dependence contributing to the most important dual substance use disorders (SUDs). Given the implications of poly-substance abuse, it is essential that clinicians and researchers be aware of potential pharmacotherapies for the treatment of dual SUDs.A substantial number of patients abuse more than one drug concurrently, complicating the treatment of SUD and leaving clinicians with few FDA-approved drug options for their patients. In this era of evidence based medicine, such patients are typically treated with therapeutically proven medications, but in ways that are outside the scope of a drug's original indication by the FDA. Such 'off-label' prescribing has become an important therapeutic strategy for practitioners seeking treatments for other diseases in subpopulations such as paediatrics and gerontology or for medical conditions such as oncology or mental illness. Similarly, the information that most clinicians use to make their decisions for treating patients abusing multiple drugs stems from trials treating a single SUD, anecdotal experiences from their own practice or that of their colleagues, or single-case studies reported in the literature. The existing evidence suggests there are few treatments for SUDs that confer significant reductions in substance use across a broad patient population. Moreover, even fewer clinical efficacy trials have been conducted that provide evidence of therapeutic benefit for these drugs. Recognising the difficulty in making the proper drug choice for facilitating maximum treatment success, this review highlights the single drugs or drug combinations that show some potential for treating dual SUDs. This review finds strongest support for the use of disulfiram for treatment of alcohol and cocaine dependence (with or without concomitant methadone maintenance), baclofen for alcohol and cocaine dependence (but not opioid-dependent cocaine users), tiagabine for cocaine dependence in methadone-maintained patients, and topiramate for alcohol, nicotine and cocaine dependence. While ondansetron and olanzapine show some efficacy in treating alcohol and cocaine dependence, more research is needed to better delineate the subpopulation in which these drugs may provide their maximum effect. PMID- 17338595 TI - Tramadol extended-release tablets in moderate to moderately severe chronic pain in adults: profile report. PMID- 17338596 TI - Gender differences in posttraumatic stress disorder. AB - One of the most consistent findings in the epidemiology of posttraumatic stress disorder (PTSD) is the higher risk of this disorder in women. Explanations reviewed within a psychobiological model of PTSD suggest that women's higher PTSD risk may be due to the type of trauma they experience, their younger age at the time of trauma exposure, their stronger perceptions of threat and loss of control, higher levels of peri-traumatic dissociation, insufficient social support resources, and greater use of alcohol to manage trauma-related symptoms like intrusive memories and dissociation, as well as gender-specific acute psychobiological reactions to trauma. This review demonstrates the need for additional research of the gender differences in posttraumatic stress. Recommendations are made for clinical practice. PMID- 17338597 TI - Toward the reduction of population obesity: macrolevel environmental approaches to the problems of food, eating, and obesity. AB - The authors reviewed the evidential basis of three environmental approaches to reducing population obesity: What are the effects of (a) taxing or subsidizing foods, (b) manipulating the ease of food access, and (c) restricting access to certain foods? A narrative review evaluated evidence using National Heart, Lung, and Blood Institute criteria. There was strong evidence that subsidization influences food purchases, but not necessarily food consumption or body weight. Ease of food access may influence food purchases, and possibly food intake and body weight. Data on restriction were lacking. More studies are needed to justify that altering these macro-environmental variables will necessarily reduce population obesity. A proposed conceptual model posits that the steps through environmental interventions may exert intended and unintended influences on body weight and obesity prevalence. Contemplated policy changes should weigh scientific evidence with social judgments and values concerning changes to the environment. PMID- 17338598 TI - Theories of artificial grammar learning. AB - Artificial grammar learning (AGL) is one of the most commonly used paradigms for the study of implicit learning and the contrast between rules, similarity, and associative learning. Despite five decades of extensive research, however, a satisfactory theoretical consensus has not been forthcoming. Theoretical accounts of AGL are reviewed, together with relevant human experimental and neuroscience data. The author concludes that satisfactory understanding of AGL requires (a) an understanding of implicit knowledge as knowledge that is not consciously activated at the time of a cognitive operation; this could be because the corresponding representations are impoverished or they cannot be concurrently supported in working memory with other representations or operations, and (b) adopting a frequency-independent view of rule knowledge and contrasting rule knowledge with specific similarity and associative learning (co-occurrence) knowledge. PMID- 17338599 TI - Anxiety, anxiety disorders, tobacco use, and nicotine: a critical review of interrelationships. AB - Smoking is highly prevalent across most anxiety disorders. Tobacco use increases risk for the later development of certain anxiety disorders, and smokers with anxiety disorders have more severe withdrawal symptoms during smoking cessation than smokers without anxiety disorders. The authors critically examined the relationships among anxiety, anxiety disorders, tobacco use, and nicotine dependence and reviewed the existing empirical literature. Future research is needed to better understand the interrelationships among these variables, including predictors, moderators, and mechanisms of action. Increased knowledge in these areas should inform prevention efforts as well as the development and improvement of smoking cessation programs for those with anxiety and other psychiatric disorders. PMID- 17338600 TI - Event perception: a mind-brain perspective. AB - People perceive and conceive of activity in terms of discrete events. Here the authors propose a theory according to which the perception of boundaries between events arises from ongoing perceptual processing and regulates attention and memory. Perceptual systems continuously make predictions about what will happen next. When transient errors in predictions arise, an event boundary is perceived. According to the theory, the perception of events depends on both sensory cues and knowledge structures that represent previously learned information about event parts and inferences about actors' goals and plans. Neurological and neurophysiological data suggest that representations of events may be implemented by structures in the lateral prefrontal cortex and that perceptual prediction error is calculated and evaluated by a processing pathway, including the anterior cingulate cortex and subcortical neuromodulatory systems. PMID- 17338601 TI - Olfactory-induced synesthesias: a review and model. AB - Recent reviews of synesthesia concentrate upon rare neurodevelopmental examples and exclude common olfactory-induced experiences with which they may profitably be compared. Like the neurodevelopmental synesthesias, odor-induced experiences involve different sensory modalities; are reliable, asymmetric (concurrents cannot induce), and automatic; and the inducer-concurrent relationship is learnt. Unlike neurodevelopmental synesthesias, these experiences are universal and their synesthetic nature goes unrecognized. Olfaction's ability to universally induce concurrents may result from its unique neuroanatomy, affording dual access to neocortex. We propose that concurrents arise here via a twofold process: by direct neocortical activation, which recovers a configural memory, and by attribution of this memory to the olfactory modality by thalamic attentional processes. The implications of this for other forms of synesthesia are then examined. PMID- 17338602 TI - The simulating social mind: the role of the mirror neuron system and simulation in the social and communicative deficits of autism spectrum disorders. AB - The mechanism by which humans perceive others differs greatly from how humans perceive inanimate objects. Unlike inanimate objects, humans have the distinct property of being "like me" in the eyes of the observer. This allows us to use the same systems that process knowledge about self-performed actions, self conceived thoughts, and self-experienced emotions to understand actions, thoughts, and emotions in others. The authors propose that internal simulation mechanisms, such as the mirror neuron system, are necessary for normal development of recognition, imitation, theory of mind, empathy, and language. Additionally, the authors suggest that dysfunctional simulation mechanisms may underlie the social and communicative deficits seen in individuals with autism spectrum disorders. PMID- 17338603 TI - The psychological implications of concealing a stigma: a cognitive-affective behavioral model. AB - Many assume that individuals with a hidden stigma escape the difficulties faced by individuals with a visible stigma. However, recent research has shown that individuals with a concealable stigma also face considerable stressors and psychological challenges. The ambiguity of social situations combined with the threat of potential discovery makes possessing a concealable stigma a difficult predicament for many individuals. The increasing amount of research on concealable stigmas necessitates a cohesive model for integrating relevant findings. This article offers a cognitive-affective-behavioral process model for understanding the psychological implications of concealing a stigma. It ends with discussion of potential points of intervention in the model as well as potential future routes for investigation of the model. PMID- 17338604 TI - M-stream deficits and reading-related visual processes in developmental dyslexia. AB - Some visual processing deficits in developmental dyslexia have been attributed to abnormalities in the subcortical M stream and/or the cortical dorsal stream of the visual pathways. The nature of the relationship between these visual deficits and reading is unknown. The purpose of the present article was to characterize reading-related perceptual processes that may link the visual deficits to reading problems. We identified contrast sensitivity, position encoding, oculomotor control, visual attention, parafoveal/foveal interactions, and saccadic suppression as potential reading-related dorsal stream processes. We then evaluated the role of each process in reading and the status of each process in dyslexia. In theory, a number of dorsal stream processes (e.g., oculomotor control and visual attention) might contribute to reading problems in developmental dyslexia. More work is needed to demonstrate the connection empirically. PMID- 17338606 TI - Safety and efficacy of ureteral access sheaths. AB - The ureteral access sheath (UAS) was introduced as a means of passing a flexible ureteroscope. Although the device was initially lauded for its ability to facilitate ureteroscopic access, passage was difficult and risked ureteral injury, and the UAS fell out of favor until the development of a new generation of devices that was easier to insert. The UAS should be advanced under fluoroscopy over a stiff guidewire, and the surgeon should ensure copious hydration of all inner and outer surfaces. Use of the UAS is purported to improve irrigant flow and visibility. The UAS can induce transient ureteral ischemia and promote an acute inflammatory response, but it also prevents potentially harmful elevations in intrarenal pressure. Unequivocal data are not yet available to suggest that UAS use during ureteroscopy protects or harms the upper urinary tract. The UAS also has the potential to improve stone-free rates by allowing passive egress or active retrieval of fragments. A large prospective study is needed to unequivocally determine if UAS use is superior in terms of stone-free rates. Cost studies reported to favor UAS use, although a formal cost effectiveness analysis has not been performed. Further study is needed before routine use of the UAS can be recommended. PMID- 17338608 TI - Impact of shockwave coupling on efficacy of extracorporeal shockwave lithotripsy. AB - PURPOSE: To evaluate the impact of a slow gated treatment rate on the efficacy of extracorporeal shockwave lithotripsy (SWL). PATIENTS AND METHODS: From August 1990 to July 2002, 40,462 SWL procedures were performed using the slow frequency electrocardiography (ECG)-gated lithotripter (82.5%) and fast frequency ECG ungated (17.5%) modes for the Medstone STS lithotripter. Treatment characteristics, including the mode of SWL, location and size of the stone, re treatment status, auxiliary procedures required, perioperative complications, and treatment outcomes, were recorded. The stone-free rate was reported by the treating physician on the basis of the finding of no residual stone fragments on a plain radiographic image. RESULTS: The treatment rate for the slow mode was a mean of 79.6 shocks/min, while the rate for the fast mode was 120/min. The total procedure time was 47.0 minutes for the slow mode and 40.6 minutes for the fast. The overall stone-free rate was higher for slow (66.9%) than fast (63.6%) procedures (P < 0.001). The stone-free rate for 1- to 10-mm stones was higher for the slow procedures (75.7%) than the fast procedures (70.7%; P < 0.001). Upper ureteral stones responded better to slow treatment in terms of stone-free rate (79.5% v 72.6%; P < 0.001), re-treatment rate (6.5% v 8.0%, P = 0.05), auxiliary procedure rate (6.1% v 8.9%; P = 0.01), and efficiency quotient (71 and 62). There was no significant difference in complication rates overall between slow and fast treatment. CONCLUSIONS: With a minimal increase in procedure time, greater efficacy can be obtained for the treatment of radiopaque stones with a slower shock-delivery rate. In particular, upper-ureteral calculi and calculi <10 mm benefit from a slower treatment rate. PMID- 17338609 TI - Pediatric shockwave lithotripsy: size matters! AB - BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) is a safe and efficacious modality for pediatric urolithiasis. Recent reports claim good results even with larger stone burdens, irrespective of stone location. We reviewed the outcomes of SWL in the pediatric population at our center to assess the impact of stone burden and location and the age of the child on the stone-free rate. PATIENTS AND METHODS: Records of 106 patients or=75 g (N = 36). The factors considered were age, body mass index, total operating time, estimated blood loss, serum prostate specific antigen (PSA) concentration, pathologic stage and Gleason grade, intraoperative and peri-operative complications, margin status, and continence. RESULTS: A statistically significant difference (P < 0.05) was noted in age (59 v 64 years), PSA concentration (6.07 v 8.9 ng/dL), and blood loss (175 v 226 mL) between patients with smaller v larger prostates. No difference was seen in Gleason score (6 v 6), clinical T stage, operative time (217 v 225 minutes), or total positive-margin rate (13% v 19%). A higher positive-margin rate was seen in patients with stage T(3) disease and larger prostates. The 6 month continence rate in patients with a prostate volume < 75 g was 97% v 84% in patients with larger prostate volumes ( P < 0.05). CONCLUSION: Although a large prostate volume is associated with a slight increase in short-term urinary complications postoperatively, it should not be considered a contraindication for the experienced surgeon. This higher risk raises the question of a possible need for longer catheterization in this subset of patients. PMID- 17338620 TI - Feasibility and outcome of retrograde endoscopy in a post-prostatectomy population. AB - PURPOSE: To determine the feasibility of retrograde endoscopy after radical retropubic prostatectomy (RRP) and its effects on post-prostatectomy continence. PATIENTS AND METHODS: We retrospectively reviewed all patients who underwent RRP at our institution between 1999 and 2005, identifying those who subsequently required endoscopic instrumentation. Patient records were examined for the interval between procedures, method of endoscopy, and continence after endoscopy compared with baseline post-prostatectomy continence. RESULTS: Twenty-one patients were identified who required endoscopic instrumentation from 4 to 49 months after RRP. Of these, 13 patients underwent ureteroscopy for stones (N = 8) or stricture disease (N = 5). In 3 cases, a ureteral access sheath was used, and in 12 cases, a ureteral stent placed postoperatively. Review of the operative reports revealed no complications or difficulty with cannulation of the ureteral orifice(s) or sheath placement. Eight patients underwent rigid cystoscopy for hematuria, removal of a foreign body, or treatment of bladder stones (N = 2 each) or for stent placement and frequency (N = 1 each). The ureter could not be identified in one case of attempted stent placement for hydronephrosis because of a distal-ureteral stone. A follow-up intravenous urogram confirmed passage of the stone and resolution of the hydronephrosis. There were no other reported difficulties with rigid cystoscopy. There was no documented change or adverse outcome regarding continence after endoscopy. CONCLUSIONS: Post-prostatectomy retrograde endoscopy is feasible for the management of common urologic pathologies. Endoscopic instrumentation across the urethrovesical anastomosis did not have an adverse effect on urinary continence. PMID- 17338621 TI - Holmium laser enucleation of the prostate: comparison of outcomes according to prostate size in 97 Japanese patients. AB - PURPOSE: To review the outcomes associated with holmium laser enucleation of the prostate (HoLEP) to identify the efficacy and safety in relation to the prostate size in subjects with symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A retrospective review was conducted of the data from 97 patients who had undergone HoLEP combined with mechanical morcellation. All patients completed both the preoperative and the 6-month postoperative assessment. The morbidity and improvement in the outcome variables were compared in groups classified according to the baseline prostate volume: <50 cm3 (group 1), >or=50 cm3-<100 cm3 (group 2), and >or=100 cm3 (group 3). RESULTS: The peak urinary flow rate (Qmax), postvoiding residual urine volume (PVR), International Prostate Symptom Score (IPSS) and quality of life (QoL) score all improved significantly after HoLEP, and no significant differences were observed among the groups. The mean total operation times were 70.3, 99.1, and 155.5 minutes for groups 1, 2, and 3, respectively (P < 0.0001 group 1 v group 2 v group 3). The mean times required to complete the enucleation and morcellation were 44.7 v 66.5 v 107.3 minutes (P < 0.0001) and 8.6 v 10.9 v 23.8 minutes (P < 0.0001), respectively. The efficacy for tissue enucleation and morcellation was 0.44 v 0.57 v 0.75 g/min (P < 0.0001) and 2.5 v 3.3 g/min (P = 0.016) v 3.2 g/min (P = 0.035). The mean hemoglobin loss after HoLEP was greater in group 3 than in group 1 (P = 0.036), but it was still low (1.8 g/dL). Major complications included bladder-muscle injury in one patient in group 2 and one in group 3 and long-lasting urinary incontinence in one patient in group 1 and one in group 2 (2.1%). No blood transfusion or transurethral resection syndrome was observed in any of the groups. CONCLUSIONS: Holmium laser enucleation is an effective treatment for symptomatic BPH independent of prostate size. PMID- 17338622 TI - Rapid communication: minimally invasive urologic surgery curricula. AB - PURPOSE: Surgical education programs are being challenged to provide comprehensive training in the ever-expanding technologies and techniques. We present dedicated training curricula for several aspects of minimally invasive urologic surgery in an effort to provide a uniform training experience for all residents. MATERIALS AND METHODS: Five components of the curricula were developed, namely, cognitive objectives, skills objectives, competency of procedures, cognitive evaluation, and proficiency or skills evaluation. RESULTS: The five components of the curriculum were defined specifically for cystoscopy and transurethral surgery, ureterorenoscopy and intrarenal surgery, renal access surgery, and laparoscopic urology. CONCLUSION: This standardized curriculum overview for minimally invasive urologic surgery is an initial attempt to define one aspect of a urology training program. We hope these curricula will serve as a basis for further discussion and development of a comprehensive urology training program. PMID- 17338623 TI - Laparoscopic ileocystoplasty: an experimental study in pigs. AB - BACKGROUND AND PURPOSE: Bladder dysfunction may lead to urinary incontinence and progressive kidney deterioration. When clinical treatment fails, bladder augmentation is the operation of choice in most cases. The purpose of this study was the standardization of the technique of videolaparoscopic ileocystoplasty in a porcine model and demonstration of a tutor-supervised learning curve. MATERIALS AND METHODS: The study was conducted on 15 Large-White male pigs (20-25 kg) that underwent ileocystoplasty with 15 cm of distal ileum shaped into a using extracorporeal technique and laparoscopic ileovesical anastomosis. Operative time, ileovesical anastomosis time, intraoperative complications, and extravasation after anastomosis were evaluated. To assess the learning curve, the animals were divided into three groups of five: group I (operated on in collaboration with a tutor), group II (treated under the supervision of tutor), and group III (without the tutor's collaboration or supervision). RESULTS: Total surgical time and ileovesical anastomosis time revealed significant differences (P < 0.05) between groups I and III (70% reduction) as well as between groups II and III (64% reduction). CONCLUSIONS: Laparoscopic ileocystoplasty in pigs is feasible without special laparoscopic material. Ten initial procedures with a tutor's help were important for technique acquisition and mastery. A sharp increase in efficiency occurs between the tenth and fifteenth procedures. These procedures should be executed at least ten times in the presence of the tutor to enable the surgeon to overcome the learning curve. PMID- 17338624 TI - Time course of nicotinamide adenine dinucleotide diaphorase staining after renal radiofrequency ablation influences viability assessment. AB - BACKGROUND AND PURPOSE: Nicotinamide adenine dinucleotide (NADH) diaphorase staining has been used to confirm cell viability or death after radiofrequency ablation (RFA) of renal tissue. The time course over which NADH staining status converts from viable to non-viable after a lethal insult has not been defined for renal RFA, but the change may not be immediate. Our objective was to assess porcine renal tissue for viability using NADH diaphorase staining at various times after RFA. MATERIALS AND METHODS: Seven pigs underwent monopolar RFA of both kidneys followed by needle biopsy of the ablation zone before and immediately after ablation and at 15-minute intervals thereafter. Initially, a single kidney was treated, and the contralateral kidney was treated 2 weeks later. Biopsies were taken from untreated renal parenchyma in a similar time course after nephrectomy to examine the effect of ischemia. All biopsy specimens, as well as representative sections of the ablation zone, were subjected to NADH staining and reviewed by a pathologist who was blinded to the tissue treatment. RESULTS: Most of the post-RFA biopsy specimens (86%) showed non-viable tissue. However, 14% of the specimens revealed viable tissue as late as 150 minutes after RFA. Therefore, none were positive. In the nephrectomy parenchyma, 92% of the biopsy specimens showed viable tissue as late as 4 hours after the onset of ischemia. CONCLUSION: Staining for NADH can establish tissue non-viability after RFA, but the timing of staining after treatment must be considered when interpreting results to avoid false positive tests. Tissue that is apparently viable by NADH staining within 2.5 hours of RFA may in fact have been ablated. PMID- 17338625 TI - Effect of pulse width on object movement in vitro using holmium:YAG laser. AB - BACKGROUND AND PURPOSE: The holmium:YAG laser is an effective modality for intracorporeal lithotripsy. The fiber tip needs to be in contact with the calculus for maximal effect. Laser energy can cause stone retropulsion, necessitating cumbersome repositioning of the fiber. We examined the effect of varying the laser pulse width on object movement in vitro. MATERIALS AND METHODS: Two experiments were conducted using a holmium:YAG laser at the 350-microsec and 700-microsec pulse-width settings. In the first experiment, one pulse was delivered to a non-fragmentable ball bearing at increasing energy settings, and object displacement was measured. In the second experiment, a train of pulses was delivered to a fragmentable soda lime phantom at increasing energy settings, and the total energy delivered before movement from the tip of the fiber was determined. RESULTS: The mean ball bearing movement was significantly greater at the 350-microsec setting with a 200-microm fiber (P < 0.0001), as well as a 400 microm fiber (P < 0.0069). More disparity in movement was noted at higher energy settings. The total energy delivered to the soda lime phantom before migration was significantly greater using the 700-microsec setting (P < 0.0018). CONCLUSIONS: Pressure waves from Ho:YAG lithotripsy are less than with other modalities, yet some retropulsion occurs. The duration of the laser pulse can influence shockwave generation and object migration. Longer pulse width results in less object movement after one shock and more energy delivery during repetitive shocks. Clinically, this regimen may reduce the need for fiber readjustment and lead to more efficient stone fragmentation. PMID- 17338626 TI - Effect of dietary control of urinary uric acid excretion in calcium oxalate stone formers and non-stone-forming controls. AB - BACKGROUND AND PURPOSE: Hyperuricosuria is a well-recognized risk factor for calcium oxalate urolithiasis. Some studies have demonstrated elevated urinary uric acid excretion in stone formers compared with non-stone-forming controls; nevertheless, these studies were limited by patient consumption of self-selected diets. With the recognition that dietary differences may induce variations in urinary uric acid excretion, we evaluated excretion of this compound in stone formers and controls consuming a standardized diet. SUBJECTS AND METHODS: A standardized formula diet was administered to 65 calcium oxalate stone formers and 61 age-matched non-stone-forming controls. During the 3 days of dietary intervention, 24-hour urine collections were obtained. Mean urinary uric acid excretion indexed to urinary creatinine was calculated for each subject, and the results in the two groups were compared. RESULTS: Stone-forming subjects did not have an elevation in urinary uric excretion compared with control subjects, with mean indexed urinary uric acid excretions of 337 +/- 64 mg/g of creatinine and 379 +/- 76 mg/g of creatinine, respectively. CONCLUSIONS: With dietary standardization, there was no observed increase in urinary uric acid excretion in our sampled populations. These findings emphasize the role of dietary factors in urinary uric acid excretion and highlight the potential value of dietary interventions. PMID- 17338627 TI - Re: Gilleran et al. Bipolar PlasmaKinetic transurethral resection of the prostate: reliable training vehicle for today's urology residents. J Endourol 2006;20:683-687. PMID- 17338632 TI - Evolutionary selection pressure and family relationships among connexin genes. AB - We suggest an extension of connexin orthology relationships across the major vertebrate lineages. We first show that the conserved domains of mammalian connexins (encoding the N-terminus, four transmembrane domains and two extracellular loops) are subjected to a considerably more strict selection pressure than the full-length sequences or the variable domains (the intracellular loop and C-terminal tail). Therefore, the conserved domains are more useful for the study of family relationships over larger evolutionary distances. The conserved domains of connexins were collected from chicken, Xenopus tropicalis, zebrafish, pufferfish, green spotted pufferfish, Ciona intestinalis and Halocynthia pyriformis (two tunicates). A total of 305 connexin sequences were included in this analysis. Phylogenetic trees were constructed, from which the orthologies and the presumed evolutionary relationships between the sequences were deduced. The tunicate connexins studied had the closest, but still distant, relationships to vertebrate connexin 36, 39.2, 43.4, 45 and 47. The main structure in the connexin family known from mammals pre-dates the divergence of bony fishes, but some additional losses and gains of connexin sequences have occurred in the evolutionary lineages of subsequent vertebrates. Thus, the connexin gene family probably originated in the early evolution of chordates, and underwent major restructuring with regard to gene and subfamily structures (including the number of genes in each subfamily) during early vertebrate evolution. PMID- 17338633 TI - Characterization of the large subunit of EcoHK31I methyltransferase by structural modeling and mutagenesis. AB - M.EcoHK31I is a naturally occurring mC5-methyltransferase with a large alpha polypeptide and a small beta polypeptide. Polypeptide alpha contains conserved motifs I-VIII and X, and polypeptide beta contains motif IX. To understand how polypeptide alpha carries out its function, a molecular model of the large domain of polypeptide alpha was generated using M.HhaI and M.HaeIII as templates. The large domain is a mixed alpha/beta structure. Residues 15-19 in motif I (Phe-Naa Gly-Naa) are conserved for cofactor binding. The key catalytic residue Cys-79 in motif IV is also conserved in comparison with other C-5 MTases. Comparing polypeptide alpha with M.HhaI and M.HaeIII revealed a unique region upstream of motif X. To understand the role of this region, 14 charged residues between R224 and E271 in the putative small domain were mutated. Activity assays indicated that most of these charges can be eliminated or changed conservatively. Among these charged residues, R224, E240, D245 and D251 may take part in proper interaction with DNA in the presence of polypeptide beta. PMID- 17338634 TI - Purification, characterization, and molecular gene cloning of an antifungal protein from Ginkgo biloba seeds. AB - A novel basic protein with antifungal activity was isolated from the seeds of Ginkgo biloba and purified to homogeneity. The protein inhibited the growth of some fungi (Fusarium oxysporum, Trichoderma reesei, and Candida albicans) but did not exhibit antibacterial action against Escherichia coli. Furthermore, this protein showed weak inhibitory activity against the aspartic protease pepsin. To design primers for gene amplification, the NH(2)-terminal and partial internal amino acid sequences were determined using peptides obtained from a tryptic digest of the oxidized protein. The full-length cDNA of the antifungal protein was cloned and sequenced by RT-PCR and rapid amplification of cDNA ends (RACE). The cDNA contained a 402-bp open reading frame encoding a 134-aa protein with a potential signal peptide (26 residues), suggesting that this protein is synthesized as a preprotein and secreted outside the cells. The antifungal protein shows approximately 85% identity with embryo-abundant proteins from Picea abies and Picea glauca at the amino acid level; however, there is no homology between this protein and other plant antifungal proteins, such as defensin, and cyclophilin-, miraculin- and thaumatin-like proteins. PMID- 17338635 TI - Maximal Ca2+i stimulation of cardiac Na+/Ca2+ exchange requires simultaneous alkalinization and binding of PtdIns-4,5-P2 to the exchanger. AB - Using bovine heart sarcolemma vesicles we studied the effects of protons and phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) on the affinity of the mammalian Na(+)/Ca(2+) exchanger (NCX1) for intracellular Ca(2+). By following the effects of extravesicular ligands in inside-out vesicles, their interactions with sites of NCX1 facing the intracellular medium were investigated. Two Na(+) gradient-dependent fluxes were studied: Ca(2+) uptake and Ca(2+) release. PtdIns 4,5-P2 binding to NCX1 was investigated in parallel. Without MgATP (no 'de novo' synthesis of PtdIns-4,5-P2), alkalinization increased the affinity for Ca(2+) and the PtdIns-4,5-P2 bound to NCX1. Vesicles depleted of phosphoinositides were insensitive to alkalinization, but became responsive following addition of exogenous PtdIns-4,5-P2 or PtdIns plus MgATP. Acidification reduced the affinity for Ca(2+)(ev); this was only partially reversed by MgATP, despite the increase in bound PtdIns-4,5-P2 to levels observed with alkalinization. Inhibition of Ca(2+) uptake by increasing extravesicular [Na(+)] indicates that it is related to H(+)(i) and Na(+)(i) synergistic inhibition of the Ca(2+)(i) regulatory site. Therefore, the affinity of the NCX1 Ca(2+)(i) regulatory site for Ca(2+) was maximal when both intracellular alkalinization and an increase in PtdIns-4,5-P2 bound to NCX1 (not just of the total membrane PtdIns-4,5-P2) occurred simultaneously. In addition, protons influenced the distribution, or the exposure, of PtdIns-4,5-P2 molecules in the surroundings and/or on the exchanger protein. PMID- 17338636 TI - A highly conserved protein secreted by the prostate cancer cell line PC-3 is expressed in benign and malignant prostate tissue. AB - In this study we characterize a novel gene on human chromosome 9 and its translation product, PC3-secreted microprotein (PSMP). The gene contains three exons that encode a protein of 139 amino acid residues, including a predicted signal peptide of 36 residues. The molecule is homologous to beta microseminoprotein (MSP), a protein of unknown function, secreted at high concentration by the prostate gland. These two proteins have only 23% sequence identity, but their common origin is revealed by a preserved pattern of Cys residues. In contrast to MSP, which shows poor conservation between species, PSMP is very conserved. High transcript levels were detected in the prostate cancer cell line PC-3. Antiserum raised against PSMP detected a protein with an apparent molecular mass of 18 kDa in culture medium conditioned by PC-3 cells, but in cell lysates the antiserum also recognized a molecular species of 16 kDa, suggesting that PSMP undergoes post-translational modification. Xenografted PC-3 cell tumors in athymic nude mice showed strong staining for both PSMP protein and mRNA. Studies on human prostate cancer specimens showed immunohistochemical staining of both tumor and benign glandular cells. Our results suggest that PSMP is an important protein with significance in prostate cancer. PMID- 17338637 TI - Properties and partial purification of sialate-O-acetyltransferase from bovine submandibular glands. AB - The O-acetylation of sialic acids in various positions is a frequent modification of these residues in glycoproteins and glycolipids of higher animals and some bacteria. Sialic acid O-acetylation is involved in the regulation of many cell biological and pathophysiological events. Since the properties and the structural and molecular genetic aspects of the eukaryotic sialate O-acetyltransferases are not yet known, we attempted to isolate the enzyme from bovine submandibular glands. O-Acetyltransferase was solubilised from its microsomal location with a zwitterionic detergent and enriched by approximately 50-fold in three steps, including affinity chromatography on coenzyme A. It exhibits a molecular mass of 150-160 kDa. Evidence was obtained for the putative existence of a low-molecular mass, dialysable enzyme activator. The enzyme showed best activity with CMP-N acetylneuraminic acid (CMP-Neu5Ac), followed by N-acetylneuraminic acid (Neu5Ac). These compounds, as well as AcCoA, have high affinity for both the microsome bound and the partially purified O-acetyltransferase. CoA is a strong inhibitor. N-Acetyl-9-O-acetylneuraminic acid was found to be the main reaction product. No evidence was obtained for the involvement of an isomerase that might be responsible for the migration of O-acetyl groups within the sialic acid side chain. PMID- 17338638 TI - Raft association and lipid droplet targeting of flotillins are independent of caveolin. AB - Lipid rafts are liquid ordered platforms that dynamically compartmentalize membranes. Caveolins and flotillins constitute a group of proteins that are enriched in these domains. Caveolin-1 has been shown to be an essential component of caveolae. Flotillins were also discovered as an integral component of caveolae and have since been suggested to interact with caveolins. However, flotillins are also expressed in non-caveolae-containing cells such as lymphocytes and neuronal cells. Hence, a discrepancy exists in the literature regarding the caveolin dependence of flotillin expression and their subcellular localization. To address this controversy, we used mouse embryonic fibroblasts (MEFs) from caveolin-1 knockout (Cav-1(-/-)) and wild-type mice to study flotillin expression and localization. Here we show that both membrane association and lipid raft partitioning of flotillins are not perturbed in Cav-1(-/-) MEFs, whereas membrane targeting and raft partitioning of caveolin-2, another caveolin family protein, is severely impaired. Moreover, we demonstrate that flotillin-1, but not flotillin-2, associates with lipid droplets upon oleic acid treatment and that this association is completely independent of caveolin. Taken together, our results show that flotillins are localized in lipid rafts independent of caveolin 1 and that translocation of flotillin-1 to lipid droplets is a caveolin independent process. PMID- 17338639 TI - On the presence of C2-ceramide in mammalian tissues: possible relationship to etherphospholipids and phosphorylation by ceramide kinase. AB - C(2)-ceramide (N-acetyl-sphingenine) is often used as an analog to study ceramide mediated cellular processes. According to Lee et al. [J. Biol. Chem. 271 (1996), 209-217], C(2)-ceramide is formed by an acetyl transfer from platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) to sphingenine. To substantiate these unconfirmed findings, we (i) developed a method to quantify C(2)-ceramide and (ii) analyzed C(2)-ceramide levels in Pex5(-/-) mice, a model for Zellweger syndrome, in which the synthesis of ether lipids such as PAF is impaired. The presence of C(2)-ceramide could be established in brain (+/-10 pmol/g) and liver (+/-25 pmol/g) from control mice, and was approximately 5000 fold less than the main long-chain ceramide species. In Pex5(-/-) mice, C(2) ceramide levels did not differ significantly compared to control tissues. Given the presence of a ceramide kinase in mammals, phosphorylation of C(2)-ceramide by human ceramide kinase (HsCERK) was tested. C(2)-ceramide appears to be a good substrate when albumin is used as carrier. In CHO cells overexpressing HsCERK, phosphorylation of exogenously added C(2)-ceramide could also be demonstrated. Our data indicate that C(2)-ceramide is present in mammalian tissues and can be converted to C(2)-ceramide-1-phosphate, in addition to other documented metabolic alterations, but does not seem to be linked to ether lipid metabolism. PMID- 17338640 TI - Specific inhibition of interleukin-13 activity by a recombinant human single chain immunoglobulin domain directed against the IL-13 receptor alpha1 chain. AB - Interleukin-13 (IL-13) is a T-cell-derived pleiotropic cytokine of particular medical importance because of its critical role in the development of allergic asthma. The effects of IL-13 on its target cells are mediated through a dimeric transmembrane receptor (IL-13R), which shares the IL-4Ralpha subunit with the IL 4R system, but contains as a specific component the IL-13Ralpha1 chain. We have generated a set of single-chain Fv fragments with specific binding capacity to the extracellular domain of the human IL-13Ralpha1 receptor. Bacteriophage clones displaying receptor-binding antibody domains were selected from both naive and synthetic libraries by repetitive panning on recombinant and cell surface expressed recombinant IL-13Ralpha1. Their specific reactivity with native human IL-13Ralpha1 expressed on the surface of transfected cells was demonstrated by flow cytometry. One binder that specifically interfered with cell activation by IL-13 was extensively characterized. This scFv inhibited IL-13-driven gene transcription and cell proliferation in test cell lines, as well as IL-13-induced activation of primary human monocytes in a dose-dependent manner, with an IC(50) below 300 nM. This novel reagent thus constitutes a valuable tool for the further elucidation of IL-13 function in disease and offers potential therapeutic perspectives. PMID- 17338641 TI - Effects of disease-modifying anti-rheumatic drugs (DMARDs) on the activities of rheumatoid arthritis-associated cathepsins K and S. AB - Rheumatoid arthritis is an inflammatory and disabling joint disease affecting 0.5 1.5% of the population. Although various anti-inflammatory (NSAIDs) and disease modifying (DMARDs) drugs are in clinical use, their precise mechanisms of action are not always defined. In this report, we discuss the effects of widely used DMARDs such as gold derivatives and chloroquine on cathepsins K and S, which have been implicated as critical mediators of inflammation and joint erosion in rheumatoid arthritis. We demonstrate that clinically potent gold derivatives inhibit cathepsins K and S in in vitro and cell-based assays. An X-ray analysis of the gold thiomalate/cathepsin K complex reveals that the inhibitor is bound to the active-site cysteine residue of the protease. Chloroquine, a lysosomotropic agent of lower clinical potency than gold derivatives, inhibits neutral pH-labile cathepsins intracellularly, but does not affect the neutral pH-stable cathepsin S. The potent inhibition of cathepsins implicated in the pathogenesis of rheumatoid arthritis by gold derivatives may explain the therapeutic efficacy of these drugs. PMID- 17338642 TI - Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease. AB - Epithelial cells in the human small intestine express meprin, an astacin-like metalloprotease, which accumulates normally at the brush border membrane and in the gut lumen. Therefore, meprin is targeted towards luminal components. In coeliac disease patients, peptides from ingested cereals trigger mucosal inflammation in the small intestine, disrupting epithelial cell differentiation and function. Using in situ hybridisation on duodenal tissue sections, we observed a marked shift of meprin mRNA expression from epithelial cells, the predominant expression site in normal mucosa, to lamina propria leukocytes in coeliac disease. Meprin thereby gains access to the substrate repertoire present beneath the epithelium. PMID- 17338643 TI - Human dipeptidyl peptidase III acts as a post-proline-cleaving enzyme on endomorphins. AB - Dipeptidyl peptidase III (DPP III) is a zinc exopeptidase with an implied role in the mammalian pain-modulatory system owing to its high affinity for enkephalins and localisation in the superficial laminae of the spinal cord dorsal horn. Our study revealed that this human enzyme hydrolyses opioid peptides belonging to three new groups, endomorphins, hemorphins and exorphins. The enzymatic hydrolysis products of endomorphin-1 were separated and quantified by capillary electrophoresis and the kinetic parameters were determined for human DPP III and rat DPP IV. Both peptidases cleave endomorphin-1 at comparable rates, with liberation of the N-terminal Tyr-Pro. This is the first evidence of DPP III acting as an endomorphin-cleaving enzyme. PMID- 17338644 TI - Transgenic mouse brains for the evaluation and quality control of BSE tests. AB - Rapid BSE tests are widely used diagnostics in veterinary medicine and more than 11 million tests are applied worldwide. The evaluation of new rapid BSE tests and the quality assurance of approved BSE tests pose a challenge owing to the natural scarcity of BSE-infected bovine brainstems and regional variations in prion titer. Transgenic mice expressing bovine prion protein (Tg4092) offer an alternative approach to these problems. To determine whether BSE-infected Tg4092 mouse brains could serve as a general standard for rapid BSE tests, we inoculated Tg4092 mice intracerebrally with BSE prions, harvested brains at defined time points post-infection and analyzed cerebral hemispheres with several approved rapid BSE tests. The results show that de novo formation of the disease-causing prion protein isoform, PrP(Sc), can be monitored during the course of infection. We demonstrate that BSE-infected Tg4092 mouse brains provide a renewable and controllable source of reference samples and suggest that such samples can generally be used for the evaluation and quality control of rapid BSE tests. PMID- 17338645 TI - Imatinib mesylate, a selective inhibitor of BCR-ABL, in chronic myeloid leukemia. PMID- 17338647 TI - Rituximab and its role as maintenance therapy in non-Hodgkin lymphoma. AB - Since rituximab, a chimeric monoclonal anti-CD20 antibody, was introduced into clinical practice in 1997, data regarding its benefit in terms of response rate, quality of response, progression-free survival and overall survival in B-cell lymphoid malignancies continues to expand. Rituximab has proven to be a relatively well-tolerated drug, with its major side effects being infusion related. Rituximab was approved initially by the US FDA and the European Medicines Agency for relapsed or refractory low-grade or follicular CD20+ B-cell non-Hodgkin lymphomas. Subsequently, its use has been extended to include first line therapy in low-grade lymphoma as well as the treatment of more aggressive histological subtypes such as diffuse large B-cell lymphoma. In this article, we review the landmark trials that have impacted clinical practice in follicular and diffuse large B-cell lymphomas and the emerging data for use of rituximab as maintenance therapy in non-Hodgkin lymphoma. PMID- 17338648 TI - Dendritic cell vaccines for leukemia patients. AB - Dendritic cells are the most professional antigen-presenting cells to elicit T cellular responses toward microbial agents and cancer cells. The graft-versus leukemia effect observed after allogeneic stem cell transplantation strongly suggests that T lymphocytes play a major role in the rejection of leukemic cells. This graft-versus-leukemia effect might be enhanced through dendritic cell vaccination. The characterization of leukemia-specific antigens eliciting immune responses in the autologous host has prompted researchers and clinicians to broaden the spectrum of dendritic cell vaccines to hematological malignancies. Recently, the focus is on acute myeloid leukemia and chronic lymphocytic leukemia. This review summarizes data on the administration of autologous and allogeneic dendritic cells to leukemia patients as an interesting approach in cellular therapy of leukemias. PMID- 17338649 TI - Treatment of acute myeloid leukemia in older patients. AB - Acute myeloid leukemia carries a dismal prognosis in patients over 60 years of age and, despite many clinical trials of both novel and conventional agents, there has been no significant improvement in overall survival during the last 30 years. Combinations of anthracyclines and cytarabine remain the cornerstone of therapy and produce complete remission in 45-55% of older patients, with a median survival of only 8-12 months. These statistics become even worse in patients over 70 years and those with unfavorable cytogenetics and/or poor performance status. Deciding which older acute myeloid leukemia patients would benefit from intensive chemotherapy is difficult and efforts are underway to improve existing risk assessment tools. Many new agents are under development, including signal transduction inhibitors, farnesyl transferase inhibitors, antibodies and novel chemotherapeutics. To date, small-molecule inhibitors and targeted therapies have had limited single-agent efficacy and have required combination with chemotherapy. The role of hematopoietic stem cell transplantation in older patients is under investigation. All patients over 60 years of age with acute myeloid leukemia should be encouraged to participate in a clinical trial if possible. PMID- 17338650 TI - Stem cell transplantation in Hodgkin lymphoma. AB - Hematopoietic stem cell transplantation is an effective treatment for patients with relapsed or refractory Hodgkin lymphoma. Treatment outcome is better among patients who demonstrate sensitivity to salvage chemotherapy. Approximately half of the patients undergoing autologous stem cell transplantation will be cured and sequential high-dose therapy has been proposed as a means of improving these results further. Lifelong medical surveillance is required following transplantation to monitor for late toxicity, including second malignancy. For young patients who relapse following transplantation, reduced-intensity allogeneic transplantation has shown encouraging response rates, while second autologous stem cell transplantation, radiotherapy and palliative single-agent chemotherapy are other options. For patients with multiple relapses and chemotherapy refractory disease, novel approaches are necessary. PMID- 17338651 TI - Thrombosis in multiple myeloma. AB - Multiple myeloma, as with other malignancies, has been associated with the development of venous thromboembolic events. Chemotherapy or steroids in combination with antiangiogenic agents can further enhance this risk. The identification of measurable factors associated with this prothrombotic state could help in the selection of patients who need antithrombotic prophylaxis. Malignancy-associated thrombophilic state, paraprotein-specific mechanisms and treatment-induced changes can explain the high rate of thrombosis in this cancer population. While the release of inflammatory cytokines induces high levels of factor VIII, von Willebrand factor and downregulate the protein C system, elevated plasma immunoglobulin can impair fibrinolysis. Strategies of thromboprophylaxis with low molecular weight heparin, warfarin or aspirin in patients treated with thalidomide/chemotherapy or lenalidomide and dexamethasone have shown efficacy. Early data indicate that the effect of low molecular weight heparin on multiple myeloma is not confined to the anticoagulant effect but could extend to survival; a similar positive trend in overall survival has also been reported in patients treated with aspirin. PMID- 17338653 TI - Combined modality treatment of laryngeal squamous cell carcinoma. AB - Squamous cell carcinoma of the larynx is a major public health concern; it causes substantial morbidity and mortality, and arises chiefly as a result of tobacco and alcohol consumption. Early stage disease is best treated with radiation or surgery alone, but for patients with more locally advanced squamous cell carcinoma of the larynx, combined modality treatment has been shown to benefit selected patients, particularly when cisplatin-based chemotherapy and concurrent radiation therapy are employed, with or without altered fractionated radiation therapy. Substantial laryngectomy-associated quality-of-life decrements can be avoided in selected, potentially resectable patients with organ-sparing approaches, without sacrificing survival. Recently, trials have addressed the role of targeted systemic agents to the epidermal growth factor receptor, and other targets are under investigation. The addition of induction chemotherapy to concurrent chemoradiotherapy is a promising treatment strategy that warrants further evaluation, but has not yet emerged as a standard of care; the toxicity of such regimens must be balanced with the potential benefits on a case-by-case basis, and functional outcomes are often quite variable. Treatment planning, management and follow-up are complex, and thus should ideally be performed in a comprehensive, multidisciplinary fashion, in a center accustomed to a high volume of such cases. Future research directions are described herein. PMID- 17338652 TI - Diagnosis and therapy of oral squamous cell carcinoma. AB - Oral squamous cell carcinoma ranks among the top ten most common cancers worldwide. Despite the success in diagnosis and therapy during the past 30 years, oral squamous cell carcinoma still belongs to the tumor types with a very unfavorable prognosis. In an effort to identify genomic alterations with prognostic relevance, we applied the comparative genomic hybridization technique on oral squamous cell carcinoma. The tumors exhibited from five up to 47 DNA copy number alterations, indicating a considerable degree of genomic imbalance. Out of 35 tumors, 19 showed a gain of chromosome band 7p12. Genomic imbalances were investigated by hierarchical cluster analysis and clustered image mapping to investigate whether genomic profiles correlate with clinical data. Results of the present investigation show that profiling of genomic imbalances in general, and especially of the epidermal growth factor receptor (EGFR) on 7p12, may be suitable as prognostic factors. In order to identify small-molecule inhibitors for EGFR, we established a database of 531 natural compounds derived from medicinal plants used in traditional Chinese medicine. Candidate compounds were identified by correlation analysis using the Kendall tau-test of IC50 values of tumor cell lines and microarray-based EGFR mRNA expression. Further validation was performed by molecular docking studies using the AutoDock program with the crystal structure of EGFR tyrosine kinase domain as docking template. We estimate these results will be a further step toward the ultimate goal of individualized, patient-adapted tumor treatment based on tumor molecular profiling. PMID- 17338654 TI - Chemokines and squamous cancer of the head and neck: targets for therapeutic intervention? AB - The biological properties of squamous carcinoma cells are intimately regulated by a multitude of cytokines and growth factors; the most well studied of these include epidermal growth factor receptor agonists and members of the transforming growth factor-beta family. The recent explosion of research in the field of chemokine function as a mediator of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in squamous carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. PMID- 17338655 TI - Function and organ preservation in adult cancers of the head and neck. AB - Treatment for primary head and neck cancer has evolved from the use of radical approaches to therapies preserving important functions. Essential to this concept is the maintenance of therapeutic efficacy. The advances of organ-sparing surgery, improved radiation techniques and fractionation, and the addition of chemotherapy and targeted systemic agents, have added to the number of patients who undergo organ-preservation therapy. Crucial functions that can be spared include speech, swallowing, vision, salivation and cosmesis. This paper examines advances in therapy that allow the preservation of these important functions, scenarios where organ and function preservation is indicated, given current technology and agents, and where there might be future improvements. PMID- 17338656 TI - Nonviral delivery vehicles for use in short hairpin RNA-based cancer therapies. AB - The use of DNA vector-based short hairpin (sh)RNA for RNA interference shows promise as a precise means for the disruption of gene expression to achieve a therapeutic effect. The in vivo usage of shRNA therapeutics in cancer is limited by obstacles related to effective delivery into the nuclei of target cancer cells. Nonviral delivery vehicles that are relevant for shRNA delivery into humans belong to a group of substances about which significant preclinical data has been amassed to show an acceptable safety profile, resistance to immune defenses and good transfection efficiency. Here, we review the most promising current nonviral gene delivery vehicles with a focus on their potential use in cancer shRNA therapeutics. PMID- 17338657 TI - Urothelial carcinoma in the prostatic urethra and prostate: current controversies. AB - We reviewed the literature on urothelial carcinoma in the prostatic urethra and prostate. We concluded that the incidence of urothelial carcinoma in the prostatic urethra and prostate is probably underestimated. This fact warrants thorough follow-up of patients with high-risk bladder cancers and also whole mount examination of the prostate after cystectomy to recognize the true incidence and extent of such tumor involvement. Resectoscope loop biopsy is the method of choice to detect urothelial carcinoma in the prostatic urethra/prostate and such biopsies should include the area around the verumontanum to ensure optimal sensitivity. Carcinoma in situ in the prostatic urethra should be treated with intravesical Bacillus Calmette-Guerin and a transurethral resection of the prostate prior to that treatment might increase the contact of Bacillus Calmette Guerin with the prostatic urethra, improve staging and in itself treat the prostatic involvement. Conservative treatment of carcinoma in situ in the prostatic ducts is an option, although radical surgery is probably best for treating extensive intraductal involvement, since data on the former strategy are inconclusive. Patients with stromal invasion should undergo radical surgery. It is necessary to take the route of prostatic involvement into account when estimating prognosis in each individual patient, since contiguous growth into the prostate is associated with worse prognosis. Prospective studies using a whole mount technique to investigate the prostate are needed to clarify both the role of different routes of prostate invasion and the prognostic significance of different degrees of prostate invasion. At cystectomy, when urothelial carcinoma is present in the prostatic urethra and/or prostate, it is necessary to balance the risk of urethral recurrence and decreased sexual function against opinion and expectations expressed by the patient during preoperative counseling regarding urinary diversion and primary urethrectomy. PMID- 17338658 TI - Metabolic modulation for cardiac protection. PMID- 17338659 TI - Acute chest pain syndrome: will MRI shake up cardiovascular care in the emergency room? PMID- 17338661 TI - Manidipine plus delapril in patients with Type 2 diabetes and hypertension: reducing cardiovascular risk and end-organ damage. AB - In patients with hypertension and diabetes, atherothrombosis is a leading cause of morbidity and mortality, and there is now compelling evidence demonstrating that lowering elevated blood pressure (BP) is one of the most beneficial aims of therapy in this high-risk population. Indeed, major international guidelines have set a target BP goal of 130/80 mmHg in high-risk patients and recommend combination treatment with two or more drug classes to help achieve this objective. Manidipine plus delapril is a fixed-dose combination of a third generation dihydropyridine calcium antagonist and an angiotensin-converting enzyme inhibitor, which is effective in mild-to-moderately hypertensive patients with an inadequate response to monotherapy. It is also effective in the long-term (50 weeks) management of essential hypertension. Comparative studies have demonstrated that manidipine plus delapril is as effective as enalapril plus hydrochlorothiazide (HCTZ) in patients with hypertension that is unresponsive to monotherapy, and as effective as ramipril plus HCTZ, valsartan plus HCTZ, irbesartan plus HCTZ and olmesartan plus HCTZ in patients with essential hypertension and Type 2 diabetes. In addition, manidipine plus delapril exhibited renoprotective effects in normotensive Type 2 diabetic patients, and improved fibrinolytic function (significantly more than irbesartan plus HCTZ) in hypertensive patients with Type 2 diabetes. Manidipine 10 mg plus delapril 30 mg once daily was generally well tolerated, with no unexpected adverse effects and evidence of a low incidence of ankle edema. Thus, manidipine plus delapril is a fixed-dose combination treatment that significantly reduces elevated BP with once daily administration. It is well tolerated and has ancillary properties, such as nephroprotective activity and improvement of fibrinolytic balance, which may help reduce cardiovascular morbidity and mortality, particularly in high-risk patients, such as those with Type 2 diabetes mellitus. PMID- 17338662 TI - Rosuvastatin: a highly potent statin for the prevention and management of coronary artery disease. AB - Since the identification of a fungal metabolite that inhibits HMG-CoA reductase in 1976, statins have emerged rapidly as the global leader in pharmacotherapeutics designed to lower low-density lipoprotein cholesterol (LDL C). In conjunction, practice guidelines have recommended increasingly aggressive measures to improve coronary heart disease (CHD) outcomes by lowering LDL-C. By virtue of unique chemical characteristics, enhanced binding thermodynamics and limited cytochrome P450 3A4 metabolism, rosuvastatin calcium has a safety profile in line with currently marketed statins, but a different efficacy profile. Mirroring this chemical profile, the GALAXY program represents a comprehensive evaluation of the efficacy, safety and cost-effectiveness of rosuvastatin in individuals representing various clinical diagnoses, pathophysiological states and ethnicities. Also results from the Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study could provide further evidence for the use of rosuvastatin in individuals with traditional and emerging CHD risk factors, such as an elevated high sensitivity C reactive protein level. This review will provide a comprehensive evaluation of the chemistry, clinical efficacy, safety and tolerability of rosuvastatin, and discuss the future role in the management of CHD and atherosclerosis. PMID- 17338663 TI - The GALAXY Program: an update on studies investigating efficacy and tolerability of rosuvastatin for reducing cardiovascular risk. AB - The GALAXY Program is a series of clinical studies investigating the efficacy and tolerability of rosuvastatin in line with the hypothesis that the statin with the greatest efficacy for improving the atherogenic lipid profile and beneficially modifying inflammatory markers will also slow progression of atherosclerosis and improve cardiovascular outcomes. Completed studies report that rosuvastatin is more effective than comparator statins in reducing low-density lipoprotein cholesterol, improving the lipid profile and enabling patients to achieve lipid goals, including revised, more stringent goals, even in high-risk patients. Studies have also reported that rosuvastatin can arrest and even regress atherosclerosis. Ongoing outcomes studies will determine whether these beneficial effects of rosuvastatin translate into reduced morbidity and mortality. PMID- 17338664 TI - Carotid artery dynamics after carotid angioplasty and stenting. AB - Carotid angioplasty and stenting (CAS) has emerged as an alternative treatment for carotid artery occlusive disease. As initial results in patients with an increased surgical risk appeared promising, the popularity of CAS has increased substantially over the last years and CAS has more often been advocated as an alternative to the gold standard, carotid endarterectomy (CEA). Several controlled trials comparing CAS with CEA are currently being conducted. However, long-term results of CAS are still sparse and several issues regarding the inherent differences between treatment modalities have not yet been elucidated. Interestingly, to date, very little attention has been directed towards the mobile features of the carotid artery and the implications of stent placement on carotid artery dynamics. PMID- 17338665 TI - Therapeutic interventions for hypertension in metabolic syndrome: a comprehensive approach. AB - Hypertension is a major component of the metabolic syndrome and a major cardiovascular risk factor. Both disorders are rapidly increasing in frequency, with hypertension affecting nearly 60 million Americans and over 1 billion people worldwide, and metabolic syndrome affecting 44% of the US population above the age of 60 years. Sedentary lifestyle, together with obesity and aging of the population, are the major contributing factors for this growing epidemic. Hypertension in metabolic syndrome possesses unique pathophysiological aspects that have considerable implications on therapy of this disease. In this article, we review the pathophysiology and provide a rationale for the current therapeutic options in light of the most recent clinical trials in the field. PMID- 17338666 TI - Percutaneous coronary intervention for left main coronary artery disease. AB - Coronary artery bypass surgery is the currently accepted treatment for unprotected left main coronary artery disease. Currently, the data supporting the safety and efficacy of stents for unprotected left main coronary disease are derived mostly from nonrandomized, single-center studies or registries. These results appear promising but large randomized trials are needed to guide therapy of this potentially lethal disease. PMID- 17338667 TI - Chronic pulmonary valve insufficiency after repaired tetralogy of Fallot: diagnostics, reoperations and reconstruction possibilities. AB - Complete correction of Tetralogy of Fallot, the most common cyanotic congenital heart defect, has now become routine. However, late residual lesions, primarily chronic pulmonary valve insufficiency, may have a negative impact on right ventricular function, leading to the need for reoperation to insert a competent valve at the right-ventricular outflow. The diagnostic modalities pertaining to the failing right ventricle, the timing for eventual reintervention and the various surgical reconstruction possibilities of the right-ventricular outflow tract are still controversial and evolving, and are reviewed with a brief overview on current trends and future outlooks. PMID- 17338668 TI - New percutaneous approaches for chronic total occlusion of coronary arteries. AB - Successful recanalization and percutaneous revascularization of coronary arteries with chronic total occlusion (CTO) is one of the 'last frontiers' in coronary interventions. Conquering this obstacle will enable complete percutaneous revascularization in an increasing number of patients. The introduction within the last few years of enhanced guidewires combined with increasing operator experience and creative procedural techniques, such as the retrograde approach and the re-entry subintimal tracking technique (STAR), have significantly reduced the number of CTOs that should now be considered unapproachable. In addition, novel devices have been developed over recent years that may increase the success rate, as well as the safety, of the procedure. The Safe-Cross radiofrequency combines optical coherence reflectometry that warns the operator when the wire tip moves to within 1 mm of the outer vessel wall, combined with radiofrequency energy pulses to facilitate the passage. The CROSSER catheter mechanically vibrates against the face of the CTO at 20 kHz at a stroke depth of approximately 20 microm, creating a channel through the CTO. The most novel approach is the biologic one, in which proteolytic enzymes that digest the CTO cap to facilitate mechanical passage. The success rates for otherwise refractory CTOs will continue to improve with the development and validation of new imaging modalities and active energy source catheters. PMID- 17338669 TI - Outcome of heart surgery procedures in octogenarians: is age really not an issue? AB - Survival rates are a well-known marker for quality performance of a cardiac surgery department, as well as standard of procedures, freedom of reoperation, postoperative complications, length of hospital stay, improvement in New York Heart Association classification and quality of life after surgery. Until recently there has not been any great interest of surgeons in topics concerning the costs of postoperative care, as long as the results were successful. However, satisfactory results after cardiac surgery in aged people require successful procedures, as well as meticulous perioperative care. The expenses of healthcare are constantly growing and approaches to optimize costs in all departments of medicine have a high priority. Exact evaluation of comorbidities and prevention of complications in aged people, as well as attentive strategies concerning expenses, may help to reduce mortality, postoperative complications and costs. PMID- 17338670 TI - Surgical therapy for heart failure. AB - Today's healthcare delivery system is challenged with an escalating number of heart failure patients who have exhausted medical therapy and overwhelmed the limits of organ transplantation. Scientific and technological advances over the last 20 years have now brought new surgical options to this vast patient population, ranging from ventricular restoration surgery to surgical gene therapy and beyond. This article reviews the myriad of surgical options that are available to these patients, their benefits and shortcomings, as well as potential future directions. PMID- 17338671 TI - Matrix metalloproteinases: influence on smooth muscle cells and atherosclerotic plaque stability. AB - Atherosclerotic plaque rupture, with subsequent occlusive thrombosis, is the underlying cause of most cases of sudden cardiac death. Matrix metalloproteinases (MMPs) are thought to mediate the progression of stable atherosclerotic lesions to an unstable phenotype that is prone to rupture through the destruction of strength-giving extracellular matrix (ECM) proteins. Smooth muscle cells secrete and deposit ECM proteins and are, therefore, considered protective against atherosclerotic plaque destabilization. However, similar to inflammatory cells (e.g., macrophages), smooth muscle cells release numerous MMPs that are capable of digesting ECM proteins. Thus, the interaction of smooth muscle cells and MMPs in atherosclerotic plaques is complex and not fully understood. Recently, research into the roles of MMPs and their endogenous inhibitors (tissue inhibitors of metalloproteinases), and their effects on smooth muscle behavior during plaque destabilization has been aided by the development of reproducible animal models of plaque instability. A plethora of studies has demonstrated that MMPs directly modulate smooth muscle behavior with both beneficial and deleterious effects on atherosclerotic plaque stability, in addition to their canonical effects on ECM remodeling. Consequently, broad-spectrum MMP inhibition may inhibit plaque-stabilizing mechanisms, such as smooth muscle cell growth, while conversely retarding ECM destruction and subsequent rupture. Hence the development of selective MMP inhibitors, that spare inhibitory effects on smooth muscle cell function, may be useful therapies to prevent plaque rupture and in this regard MMP-12 appears to be a particularly attractive target. PMID- 17338672 TI - Preeclampsia and future cardiovascular risk. AB - Pregnancy is a metabolic and vascular 'stress test' for women and those who 'fail' are at increased risk of long-term cardiovascular complications. Specifically, women who develop preeclampsia (and/or other manifestations of placental dysfunction) are at increased risk of coronary heart disease, stroke and cardiovascular disease in general. The risk is highest among women who develop both maternal (e.g., hypertension and proteinuria) and fetal (e.g., intrauterine growth restriction) manifestations of abnormal placentation, especially with preterm delivery. Most women who develop a maternal placental syndrome return to a normal clinical state in the weeks following pregnancy and their absolute risk of cardiovascular disease in the short term is very low. However, perhaps having a placentally complicated pregnancy affords women the opportunity to personalize risk and take action. Action is needed. The fact that we, as a population, are getting heavier and more sedentary is an urgent public health issue. The American Heart Association recommends that all women (even those at low cardiovascular risk) pursue dietary and lifestyle changes, in addition to smoking cessation. Engaging women of child-bearing age who may be motivated by a complicated pregnancy would be very valuable, from a public health perspective, given the prevalence and importance of cardiovascular disease in women, and the central role of the woman as caregiver to children, spouses and other family members. PMID- 17338673 TI - Exploring the natural history of atherosclerosis with intravascular ultrasound. AB - Intravascular ultrasound has emerged as the preferred imaging modality for the characterization of atherosclerotic plaque within the coronary arteries. Ultrasonic imaging reveals the presence of more extensive atheroma than suggested by conventional angiography in patients with coronary artery disease. The ability to precisely quantify atheroma volume in an arterial segment at different time points provides the unique opportunity to investigate the factors that influence the natural history of atheroma progression. Accordingly, serial intravascular ultrasound has been incorporated into a number of clinical trials that have evaluated the impact of medical therapies that modify established risk factors and novel pathological targets. This article will review the increasing role of imaging modalities in the assessment of atherosclerosis and factors that influence its natural history. PMID- 17338674 TI - Cardiovascular MRI: its current and future use in clinical practice. AB - Cardiovascular magnetic resonance (CMR) imaging is a comprehensive clinical tool for assessing a large variety of cardiovascular diseases. Using the clinical service of the Duke Cardiovascular Magnetic Resonance Center as an example, we describe how to perform image contractile function, myocardial perfusion at stress and rest, myocardial viability, cardiovascular morphology, vascular anatomy and blood flow tests. The emergence of successful dedicated CMR services presents an opportunity to optimize patient throughput by streamlining the user interface of CMR scanners, standardizing the viewing format and reporting software, and customizing training programs to focus on the standardized CMR approaches. Accordingly, we discuss potential pathways to create these standards. Finally, we discuss several promising new CMR techniques we expect will complement existing clinical procedures. PMID- 17338675 TI - Vasopressin antagonists in the management of heart failure. AB - Vasopressin antagonists have been studied in a variety of clinical settings, including patients with acute and chronic heart failure. The clinical trials published to date have sought to describe the clinical and physiologic effects of these agents in an effort to prove clinical efficacy and safety. A variety of agents with varying effects on V2 and V1a vasopressin receptor subtype have been studied. They have been shown to reduce bodyweight and improve serum sodium without worsening renal function. They may also decrease the need for loop diuretic use and may be particularly useful in patients with hyponatremia in the setting of volume overload. Further studies are underway that are powered to assess for morbidity and mortality benefits. The beneficial effects have been well documented but, until outcomes are understood more fully, the use of these agents should be limited to currently approved indications. In the USA, this includes only the treatment of euvolemic hyponatremia. PMID- 17338676 TI - Heart failure: metabolic derangements and therapeutic rationale. AB - In the USA, over two-thirds of patients with heart failure (HF) are cared for by primary care practitioners exclusively. Significant progress has been made through basic science and clinical research focusing on the prevention of HF via control of known risk factors. There has also been a great deal of progress in both pharmacologic and nonpharmacologic management of the disease. These therapeutic interventions, however, continue to be underutilized, with seemingly inadequate translation of new evidence and updated guidelines (American College of Cardiology/American Heart Association, European Society of Cardiology, Canadian Cardiovascular Society, and Heart Failure Society of America updates in 2005-2006) into clinical practice. In this review, we discuss the pathophysiology of HF in addition to the metabolic derangements and therapeutic rationale surrounding current treatment options, with a particular focus on the interventions that have been shown and recommended in updated guidelines to prevent the disease or halt its progression. PMID- 17338677 TI - Drug-induced immunomodulation to affect the development and progression of atherosclerosis: a new opportunity? AB - Inflammation and cytokine pathways are crucial for the development and progression of atherosclerotic lesions. In this review, the hypothesis that immunomodulatory drugs provide a possible therapeutic modality for cardiovascular disease is evaluated. Therefore, after a short overview of the specific inflammatory pathways involved in atherosclerosis, literature on the effect of several immunomodulatory drugs, such as nonsteroidal anti-inflammatory drugs, specific cyclooxygenase inhibitors and immunosuppressive drugs, used currently in the prevention of rejection after organ transplant, on the development and progression of atherosclerosis is reviewed. In addition, the pleiotropic immunomodulatory effect of two established cardiovascular drugs (angiotensin converting enzyme inhibitors and statins) is discussed. PMID- 17338678 TI - Transient arrest in proteasomal degradation during inhibition of translation in the unfolded protein response. AB - The UPR (unfolded protein response) activates transcription of genes involved in proteasomal degradation. However, we found that in its early stages the UPR leads to a transient inhibition of proteasomal disposal of cytosolic substrates (p53 and p27kip1) and of those targeted to ER (endoplasmic reticulum)-associated degradation (uncleaved precursor of asialoglycoprotein receptor H2a). Degradation resumed soon after the protein synthesis arrest that occurs in early UPR subsided. Consistent with this, protein synthesis inhibitors blocked ubiquitin/proteasomal degradation. Ubiquitination was inhibited during the translation block, suggesting short-lived E3 ubiquitin ligases as candidate depleted proteins. This was indeed the case for p53 whose E3 ligase, Mdm2 (murine double minute 2), when overexpressed, restored the degradation, whereas a mutant Mdm2 in its acidic domain restored the ubiquitination but did not completely restore the degradation. Inhibition of proteasomal degradation early in UPR may prevent depletion of essential short-lived factors during the translation arrest. Stabilization of p27 through this mechanism may explain the cell cycle arrest in G1 when translation is blocked by inhibitors or by the UPR. PMID- 17338679 TI - The inositol 1,4,5-trisphosphate receptor (Itpr) gene family in Xenopus: identification of type 2 and type 3 inositol 1,4,5-trisphosphate receptor subtypes. AB - Studies in the Xenopus model system have provided considerable insight into the developmental role of intracellular Ca2+ signals produced by activation of IP3Rs (inositol 1,4,5-trisphosphate receptors). However, unlike mammalian systems where three IP3R subtypes have been well characterized, our molecular understanding of the IP3Rs that underpin Ca2+ signalling during Xenopus embryogenesis relate solely to the original characterization of the 'Xenopus IP3R' cloned and purified from Xenopus laevis oocytes several years ago. In the present study, we have identified Xenopus type 2 and type 3 IP3Rs and report the full-length sequence, genomic architecture and developmental expression profile of these additional IP3R subtypes. In the light of the emerging genomic resources and opportunities for genetic manipulation in the diploid frog Xenopus tropicalis, these data will facilitate manipulations to resolve the contribution of IP3R diversity in Ca2+ signalling events observed during vertebrate development. PMID- 17338680 TI - Structure and ligand-binding site characteristics of the human P2Y11 nucleotide receptor deduced from computational modelling and mutational analysis. AB - The P2Y11-R (P2Y11 receptor) is a less explored drug target. We computed an hP2Y11-R (human P2Y11) homology model with two templates, bovine-rhodopsin (2.6 A resolution; 1 A=0.1 nm) and a hP2Y1-ATP complex model. The hP2Y11-R model was refined using molecular dynamics calculations and validated by virtual screening methods, with an enrichment factor of 5. Furthermore, mutational analyses of Arg106, Glu186, Arg268, Arg307 and Ala313 confirmed the adequacy of our hP2Y11-R model and the computed ligand recognition mode. The E186A and R268A mutants reduced the potency of ATP by one and three orders of magnitude respectively. The R106A and R307A mutants were functionally inactive. We propose that residues Arg106, Arg268, Arg307 and Glu186 are involved in ionic interactions with the phosphate moiety of ATP. Arg307 is possibly also H-bonded to N6 of ATP via the backbone carbonyl. Activity of ATP at the F109I mutant revealed that the proposed p-stacking of Phe109 with the adenine ring is a minor interaction. The mutation A313N, which is part of a hydrophobic pocket in the vicinity of the ATP C-2 position, partially explains the high activity of 2-MeS-ATP at P2Y1-R as compared with the negligible activity at the P2Y11-R. Inactivity of ATP at the Y261A mutant implies that Tyr261 acts as a molecular switch, as in other G-protein coupled receptors. Moreover, analysis of cAMP responses seen with the mutants showed that the efficacy of coupling of the P2Y11-R with Gs is more variable than coupling with Gq. Our model also indicates that Ser206 forms an H-bond with Pgamma (the gamma-phosphate of the triphosphate chain of ATP) and Met310 interacts with the adenine moiety. PMID- 17338681 TI - Autologous cultured fibroblast injection for facial contour deformities: a prospective, placebo-controlled, Phase III clinical trial. AB - BACKGROUND: Previous data indicate that injections of autologous fibroblasts increase collagen formation, accompanied by a concomitant increase in thickness and density of dermal collagen. OBJECTIVE: The purpose of this study was to determine efficacy and side effects of autologous living fibroblast injections versus placebo in a randomized Phase III trial for the treatment of various facial contour defects. METHODS: This was a double-blind, randomized comparison of injectable living autologous fibroblast cells and placebo for the treatment of facial contour defects (N=215). Live fibroblasts (20 million/mL) or placebo (the transport medium without living cells) were given as three doses administered at 1- to 2-week intervals. Efficacy evaluations were performed 1, 2, 4, 6, 9, and 12 months after the first injection. RESULTS: Living fibroblasts produced statistically significantly greater improvements in dermal deformities and acne scars than did placebo. The difference between live fibroblast injections and placebo achieved statistical significance at 6 months (p<.0001). At 9- and 12 month follow-up, live fibroblast-treated patients continued to demonstrate benefit from treatment with response rates of 75.0 and 81.6%, respectively. No serious treatment-related adverse events were reported. CONCLUSIONS: Our results indicate that autologous fibroblast injections can safely and effectively produce improvements in rhytids, acne scars, and other dermal defects continuing for at least 12 months after injection. PMID- 17338682 TI - Superimposed elastic stockings: pressure measurements. AB - BACKGROUND: High-compression stockings over 40 mmHg are often difficult or even impossible to apply. A specific technique is frequently used to overcome this problem: a high-compression stocking is replaced by two or even three lower compression stockings that are applied on top of each other, thereby reducing the effort of application. To our knowledge, however, no study concerning therapeutic stockings has demonstrated that the forces exerted by two or three superimposed stockings are additive. OBJECTIVE: The objective was to evaluate if the pressures exerted by two or three superimposed elastic stockings are additive. MATERIAL AND METHODS: A series of measurements was performed in vitro using an apparatus fitted with a pressure sensor on four different premade elastic stockings applied separately and then superimposed. The actual pressure measurement obtained with superimposed stockings was compared to arithmetic sum of the pressures produced by each of the stockings used. RESULTS: The pressures produced by superimposed stockings are adequately predicted from the pressure given by each of the stockings used in the superposition, with correlation coefficients higher than 0.9. CONCLUSION: Under our experimental conditions, the superimposed elastic stocking pressures additivity hypothesis is confirmed. In vivo studies should be conducted to confirm those results. PMID- 17338683 TI - Outcomes and side effects of duplex-guided sclerotherapy in the treatment of great saphenous veins with 1% versus 3% polidocanol foam: results of a randomized controlled trial with 1-year follow-up. AB - BACKGROUND: Eighty subjects were treated with either 1 or 3% polidocanol foam to compare the efficacy and adverse sequelae of each concentration of polidocanol foam. OBJECTIVE: The objective was to compare the effects of two different concentrations of polidocanol foam. MATERIAL AND METHODS: During a 6-month period, we treated 80 consecutive patients with primary incompetent great saphenous veins in combination with saphenofemoral junction incompetence. These patients were treated with foam of either 1 or 3% polidocanol. Duplex analyses were made before treatment and in follow-up visits to determine the presence or absence of reflux. RESULTS: After 1 year, there was a clinically relevant difference in percentage of patients with occlusion of the treated great saphenous vein between both groups: 69.5% in the 1% foam group versus 80.1% in the 3% foam group; however, this difference was not statistically significant (p=.249). After 1 year of follow-up, patients in the 3% polidocanol group noticed a larger cosmetic improvement than patients in the 1% group. CONCLUSIONS: In the treatment of primary incompetent greater saphenous veins, 3% polidocanol foam seems to be more effective than 1% polidocanol foam. The side effects were approximately similar in both groups. PMID- 17338684 TI - Patterns of saphenous venous reflux in women presenting with lower extremity telangiectasias. AB - BACKGROUND: Telangiectasias have been treated with sclerotherapy without concomitant assessment or treatment of saphenous veins. OBJECTIVE: To clarify if ultrasound (US) mapping of saphenous veins is justifiable, this investigation determined prevalence of specific patterns of saphenous vein reflux in women with telangiectasias. METHODS: US mapping of the great and small saphenous veins (GSV, SSV) was performed in 1,740 extremities of 910 consecutive patients, mostly women (86%). A subgroup of 269 limbs of women with telangiectasias (CEAP C1 class) was included in this study. Patterns of GSV and SSV reflux were classified as perijunctional, proximal, distal, segmental, multisegmental, and diffuse. RESULTS: Reflux was detected in 125 extremities (46%): 5% had reflux in both the GSV and the SSV, 39% had GSV reflux, and 2% had SSV reflux. The most common pattern of GSV reflux was segmental (73%, 87/119). Prevalence of reflux was significantly greater in GSV versus SSV (p < .001). GSV segmental plus distal reflux (40%, 108/269) was significantly more prevalent than saphenofemoral junction or near junction reflux (4%, 11/269; p < .001). CONCLUSIONS: US mapping of the GSV in women with telangiectasias is justifiable, even in asymptomatic extremities. Further research will determine if segmental reflux should be treated to avoid evolution to severe valvular insufficiency. PMID- 17338685 TI - Fractional resurfacing for the treatment of hypopigmented scars: a pilot study. AB - BACKGROUND: Treatments for hypopigmented scars have shown limited efficacy and variable safety profiles. OBJECTIVE This study evaluated the safety and efficacy of fractional resurfacing (1,550-nm Fraxel SR laser, Reliant Technologies, Mountain View, CA) for the treatment of hypopigmented scars on the face in seven patients. MATERIALS AND METHODS: Seven patients with hypopigmented scars on the face received between two and four successive treatments at 4-week intervals with the 1,550-nm Fraxel SR laser. Energy settings ranged from 7 to 20 mJ and a total density of 1,000 to 2,500 microthermal zones per square centimeter. Digital photographs were taken before each treatment and at 4 weeks after the last treatment. Independent physician clinical assessments were performed. RESULTS: Independent physician clinical assessment 4 weeks after the final Fraxel SR laser treatment revealed improvements of 51% to 75% in hypopigmentation in six of seven patients. One patient had only 26% to 50% improvement in hypopigmentation. Additionally, clinical improvements were noted in the overall texture of the treated skin. The patient's degree of satisfaction paralleled the physician's assessment of improvement. All patients reported improvement in hypopigmentation lasting greater than 3 months after the last treatment. Side effects were limited to mild pain during the treatment and mild posttreatment erythema and edema, which resolved in 2 to 4 days. CONCLUSION: Fractional resurfacing is a potentially effective modality for the treatment of hypopigmented scarring on the face. No adverse effects were observed. PMID- 17338686 TI - The use of fractional laser photothermolysis for the treatment of atrophic scars. AB - BACKGROUND: Patients with atrophic scars commonly seek treatment for their removal but are often concerned about the prolonged recovery, short-lived results, and/or ineffectiveness of available therapies. A novel treatment using a 1,550-nm erbium-doped fiber laser to induce fractional photothermolysis of treated skin has been used to resurface photodamaged skin but has not been studied previously in patients with atrophic scars to determine its effectiveness for this condition. PURPOSE: To determine the effectiveness and safety of 1,550 nm erbium-doped fiber laser treatment on atrophic scars. METHODS: Fifty-three patients (skin phototypes I-V) with mild to moderate atrophic facial acne scars received monthly treatment with a 1,550-nm erbium-doped fiber laser (Fraxel, Reliant Technologies Inc., San Diego, CA). Clinical response to treatment was determined at each treatment visit and 6 months after the final treatment session by two independent assessors using a quartile grading scale. Side effects and patient satisfaction were monitored at each follow-up visit. RESULTS: Clinical improvement averaged 51% to 75% in nearly 90% of patients after three monthly laser treatments. Mean improvement scores increased proportionately with each successive laser session. Clinical response rates were independent of age, gender, or skin phototype. Side effects included transient erythema and edema in most patients, but no dyspigmentation, ulceration, or scarring. CONCLUSIONS: Atrophic scars can be effectively and safely reduced with 1,550-nm erbium-doped fiber laser treatment. PMID- 17338687 TI - Treatment of wrinkles and elastosis using vacuum-assisted bipolar radiofrequency heating of the dermis. AB - BACKGROUND: Reduction of wrinkles is increasingly becoming one of the most sought after aesthetic procedures. A variety of treatment modalities are available for this application, including radiofrequency energy in various modes of action. OBJECTIVE: The goal of the reported study was to evaluate the safety and efficacy of a new device, which implements an innovative combination of bipolar radiofrequency and vacuum. METHODS: Forty-six healthy adults at two clinics underwent eight facial treatments every 1 to 2 weeks. For 6 months after treatment, patients were assessed directly by two evaluators at each clinic (the treating physician and an additional reviewer) using standard evaluation tools the Fitzpatrick-Goldman Classification of Wrinkling and Degree of Elastosis and a visual analog scale. RESULTS: Significant improvement in the skin's appearance and texture was observed during the treatment course and continued to increase during the follow-up period. The mean elastosis score on the wrinkling and elastosis scale before treatment was 4.5 and was reduced to less than 2.5 by 6 months after treatment, representing a drop of an entire wrinkle class (from II to I) on this scale. The reported pain levels were low, and the subjects expressed their satisfaction with the treatment and its outcome. The adverse responses consisted mainly of transient erythema and burn/blistering; there were also a few occurrences of edema, purpura, and crusting and one transient hyperpigmentation. No permanent complications had occurred. CONCLUSIONS: Our results demonstrate the safety and efficacy associated with use of this radiofrequency and vacuum device, employing Functional Aspiration Controlled Electrothermal Stimulation (FACES) technology, for reduction of facial wrinkles and elastosis. PMID- 17338688 TI - The treatment of syringomas by CO(2) laser using a multiple-drilling method. AB - BACKGROUND: Syringomas are relatively common benign adnexal tumors, predominantly developing in middle-aged women. They frequently involve the periorbital areas and cause cosmetic problems. Up to now, various treatment modalities such as electrodesiccation, laser ablation, cryosurgery, and some chemical peelings have been tried. All of them, however, have the possibilities of frequent recurrences and postoperative complications such as scarring or pigmentary changes. OBJECTIVES: The objective of this study was to determine the effectiveness of a multiple-drilling method in the treatment of syringomas. METHODS: We tried a new multiple-drilling method using CO(2) laser for 11 patients having syringomas. Clinical improvement and complications were evaluated by medical records and pre- and postlaser photograph review. RESULTS: All patients had good or excellent cosmetic results. No complications, such as scarring, erythema, and pigmentary changes, were observed. CONCLUSION: The multiple-drilling method by CO(2) laser might be an alternative to gain good cosmetic results without complications if applied repeatedly. The authors have indicated no significant interest with commercial supporters. PMID- 17338689 TI - Effect of subcutaneous infiltration anesthesia on pain in photodynamic therapy: a controlled open pilot trial. AB - BACKGROUND: Photodynamic therapy (PDT) has been established as a treatment option for nonmelanoma skin cancer, such as superficial basal cell carcinoma, actinic keratoses, or Bowen's disease. OBJECTIVE: A major drawback of PDT is pain during treatment that can cause extreme distress for some patients. METHODS: This study was a controlled, open trial comparing PDT in 16 patients on one side of the face with orally administered analgesics and PDT on the contralateral side of the face with subcutaneous infiltration anesthesia (SIA). The 5-aminolevulinic acid gel was applied 5 hours before treatment. Pain was assessed by the patient using a visual analog scale directly after treatment. RESULTS: Fifteen of 16 (94%) patients reported less pain during PDT after SIA compared to oral analgesics only. This effect was significant (Wilcoxon test for matched pairs, p= .001). No side effects due to SIA were observed. CONCLUSION: SIA is an effective and rather safe method for the control of PDT-associated pain. PMID- 17338690 TI - Topical imiquimod as an adjuvant to laser removal of mature tattoos in an animal model. AB - BACKGROUND: Lasers are a commonly employed method of tattoo removal; however, numerous treatments are often needed and laser treatment may fail to eliminate the tattoo completely. It has been shown in animal studies that topical application of imiquimod cream, alone, fades tattoos. It is suspected that the combination of both imiquimod and laser treatment will result in enhanced tattoo pigment clearance. OBJECTIVE: The objective was to evaluate the efficacy of topical imiquimod cream as an adjuvant to laser removal of mature tattoos. METHODS: Fourteen albino guinea pigs were tattooed with black ink, then randomly assigned into two groups: one underwent sequential laser treatments with a Q switched alexandrite laser in conjunction with triweekly applications of 5% imiquimod cream, while the other group underwent laser therapy alone. Subjects were evaluated with clinical photographs and skin biopsies after six laser treatment sessions. RESULTS: The combination laser and imiquimod treated group was clinically and histologically rated as having less pigment than the tattoos that were treated with laser alone (p=.012 and p=.047, respectively). Adjuvant imiquimod treatment had greater inflammation (p=.002) and fibrosis (p=.002) on posttreatment skin biopsies. CONCLUSION: Imiquimod appears to be a useful adjuvant to experimental laser tattoo removal in guinea pigs. PMID- 17338691 TI - Superficial dermabrasion and suction blister epidermal grafting for postburn dyspigmentation in Asian skin. AB - BACKGROUND The effective treatment of postburn dyspigmentation, which is more common in non-Caucasian populations, is a challenge for all surgeons. OBJECTIVE We tried to evaluate an alternative surgical method of superficial dermabrasion and suction blister epidermal grafting, its efficacy, and its outcome, for the treatment of postburn dyspigmentation disorders in Asians. METHODS We applied superficial dermabrasion as a deepithelialization process on dyspigmented areas of skin and simultaneous suction blister epidermal grafting to providing pure epidermis. Twenty-three cases were included in our study. RESULTS All of the epidermal grafts took completely within 4 or 5 days after surgery without hematoma or delayed wound healing in any case. Skin color and surface irregularity improved remarkably in all cases and blended in well with the surrounding skin. Postoperative complications, such as peripheral hypopigmentation, delayed hyperpigmentation, milia, inclusion cysts, achromic fissures, prolonged erythema, and scar deformity, were not observed in any of the cases during the follow-up period. CONCLUSION Our method of combined modalities had a synergistic effect on the treatment of postburn dyspigmentation. The authors suggest that superficial dermabrasion with simultaneous epidermal grafting should be considered as an alternative method for the treatment of postburn dyspigmentation disorders. PMID- 17338692 TI - Mohs micrographic surgery in the treatment of rare aggressive cutaneous tumors: the Geisinger experience. AB - BACKGROUND: Mohs micrographic surgery (MMS) offers high cure rates and maximum tissue preservation in the treatment of more common cutaneous malignancies, but its effectiveness in rare aggressive tumors is poorly defined. OBJECTIVE: Evaluate the effectiveness of MMS in the treatment of six rare aggressive cutaneous malignancies as seen by Mohs surgeons working at a referral center. METHODS: Retrospective chart review of 26,000 cases treated with MMS at the Geisinger Medical Center Department of Dermatology during a 16-year period with the following diagnoses: poorly differentiated squamous cell carcinoma (PDSCC), dermatofibrosarcoma protuberans (DFSP), microcystic adnexal carcinoma (MAC), extramammary Paget's disease (EMPD), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SEB CA). Patient demographic data, tumor measurements, treatment characteristics, and marginal recurrence rates were compiled and evaluated. RESULTS: The mean numbers of cases identified per year for each tumor type were as follows: PDSCC, 6.19; DFSP, 2.44; MAC, 1.63; and EMPD, 0.63. For PDSCC, 85 cases were available for follow-up with a local recurrence rate of 6% at a mean follow-up time of 45 months. For DFSP, there were 35 cases with no local recurrence at a mean follow-up of 39 months. For MAC, there were 25 cases with a local recurrence rate of 12% at a mean follow-up of 39 months. For EMPD, there were 10 cases with no local recurrences at a mean follow-up of 34 months. CONCLUSIONS: Collectively, our data on PDSCC, DFSP, MAC, and EMPD, combined with other studies in the literature, show that MMS is the most effective therapy for these rare aggressive cutaneous malignancies. PMID- 17338693 TI - Giant pilomatrixoma (benign calcifying epithelioma of Malherbe) of the neck and face. PMID- 17338694 TI - "Beak"-plasty: a new effective modification of Z-plasty. AB - BACKGROUND: Because the "lateral limbs" resulting from conventional Z-plasty form a steep angle against the relaxation skin tension line (RSTL), they often develop hypertrophic change, whereas the "central limbs" become inconspicuous after being realigned parallel to the RSTL. OBJECTIVE: To alleviate the above-mentioned hypertrophic change of the lateral limbs, we modified the conventional Z-plasty and invented a new technique. Because the shape of the flap resembles a bird's beak, we call the technique "beak-plasty." The purpose of this study is to present the new technique. METHODS: The technique is described and effectiveness of the technique is reviewed on 21 patients. In particular, three representative cases are presented with photographs. RESULTS: In all patients, the lateral limbs of the flaps did not become hypertrophic after a minimum follow-up period of 9 months. CONCLUSIONS: Our technique can effectively reduce Z-plasty's risk of postoperative hypertrophy in the lateral limb. Therefore, it can make the scar less conspicuous than in conventional Z-plasty. For this advantage, we recommend our technique as an effective armament for scar revision. The authors have indicated no significant interest with commercial supporters. PMID- 17338695 TI - Island pedicle flaps for the repair of a nose, cheek, and lip defect. PMID- 17338697 TI - Successful management of an unusual presentation of impending necrosis following a hyaluronic acid injection embolus and a proposed algorithm for management with hyaluronidase. PMID- 17338698 TI - Treatment of inverse psoriasis with excimer therapy and tacrolimus ointment. PMID- 17338699 TI - Malignant perifollicular atypical fibroxanthoma treated with Mohs surgery. PMID- 17338700 TI - Double purse-string closure for scalp and extremity wounds. PMID- 17338701 TI - Eccrine porocarcinoma: a rare but sometimes fatal malignant neoplasm. PMID- 17338702 TI - Microcystic adnexal carcinoma in the nasolabial area: resection and reconstruction with a free fasciocutaneous lateral arm flap with a sandwich technique. PMID- 17338703 TI - Lipoma of the index finger. PMID- 17338704 TI - Mohs micrographic surgery for a problematic infantile digital fibroma. PMID- 17338705 TI - Letter: Mohs micrographic surgery for the treatment of vulvar Bowen's disease. PMID- 17338706 TI - Letter: brachial plexopathy from tumescent anesthesia? PMID- 17338707 TI - Letter: efficacy of a self-made artificial skin in the treatment of chronic ulcers. PMID- 17338708 TI - The precordial thump: convertio cordis, commotio cordis, or neither? PMID- 17338709 TI - Ineffectiveness of precordial thump for cardioversion of malignant ventricular tachyarrhythmias. AB - BACKGROUND: The Precordial Thump (PT) is commonly used for cardiopulmonary resuscitations both in and out of hospitals. However, the support for its efficiency relies mainly on sporadic cases. In this current prospective large study, we tested the effectiveness and safety of PT in a wide range of malignant ventricular tachyarrhythmias. METHODS: The study included 80 patients who underwent electrophysiological study and/or implantation of a cardiodefibrillator device. During these procedures, once a malignant ventricular tachyarrhythmia was induced, PT was used as the first treatment option. If the PT failed, other means were used to discontinue the arrhythmia. RESULTS: Polymorphic ventricular tachycardia occurred in 32 (40%) patients, ventricular fibrillation in 28 (35%) patients, and 20 (25%) patients had sustained monomorphic ventricular tachycardia. Except in one patient with monomorphic ventricular tachycardia, the PT was unsuccessful in terminating any of the other malignant tachyarrhythmias, and internal or external defibrillation was eventually required in all other 79 (99%) patients. The PT was not associated with any damage either to the sternal bone, ribs, or to the cardiodefibrillator device. CONCLUSIONS: PT is not effective in terminating malignant ventricular tachyarrhythmia and should be reserved to a situation in which a defibrillator is not available. PMID- 17338710 TI - Effect of programmed number of intervals to detect ventricular fibrillation on implantable cardioverter-defibrillator aborted and unnecessary shocks. AB - INTRODUCTION: Detection of self-terminating arrhythmias by implantable cardioverter-defibrillators (ICDs) causes unnecessary battery depletion and unnecessary shocks. Our goal was to estimate the effect of the programmed number of intervals to detect (NID) ventricular fibrillation (VF) on ICD temporal episode rate, unnecessary shocks, and delay in detection of VF. METHODS AND RESULTS: We analyzed 773 ICD-detected VF episodes in 875 patients. The number of intervals to detect VF was programmed to 12 of 16 (NID 12) in 305 patients and 18 of 24 (NID 18) in 570 patients. For patients with NID 12, we estimated the increase of mean cumulative episode rate at 6 months since implant and decrease in detection time for VF compared with a hypothetical NID 18. For patients with NID 18, we estimated the decrease of mean cumulative episode rate and unnecessary shocks compared with a hypothetical NID 12. Patients with NID 12 had a 17% increased episode rate resulting in unnecessary capacitor charging for self terminating arrhythmias. Patients with NID 18 had a 22% decreased episode rate. In patients with NID 12, hypothetical NID 18 would have delayed detection of 273 VF episodes in 1.8 seconds. In patients with NID 18, hypothetical NID 12 would have resulted in inappropriate delivery of 14 aborted shocks in 10% of patients with episodes. CONCLUSION: In patients with self-terminating device-detected VF, increasing the number of intervals to detect VF from 12/16 to 18/24 results in a clinically significant decrease in ICD detections and fewer unnecessary shocks with minimal incremental delay in VF detection. PMID- 17338711 TI - A percutaneous catheter-based system for the measurement of potential gradients applicable to the study of transthoracic defibrillation. AB - BACKGROUND: The local electric (E) field or potential gradient produced by a shock reliably predicts VF termination. In this study we evaluated a multiple electrode, catheter-based device for closed-chest 3D measurements of E field from transthoracic defibrillation shocks. METHODS: Catheters with multiple electrodes on the tip were placed in intracardiac locations in anesthetized swine. An empirically derived calibration matrix and custom microprocessor was used to transform simultaneously measured voltages into orthogonal E field vector components. E fields produced in six intracardiac locations by 30 and 300 J shocks were compared in eight animals. Correlations were determined for measured current and E field at various shock strengths at two different transthoracic impedances in five additional animals. VF was induced in 12 animals and E field measured during defibrillation attempts. RESULTS: The E field measurements resulting for 30 J transthoracic shocks were not significantly different among different intracardiac sites. At 300 J, however, significant differences were observed between sites with the greatest intensities recorded in the coronary sinus and right ventricle. Within animals, the variability of the measurement at each site was small, ranging from 2.8 +/- 1.6% to 5.7 +/- 4.5%. Significant correlations (P < 0.001) between measured E field and peak current were observed at native impedance (34 +/- 4 Omega, r = 0.81) and at adjusted impedance (76 +/- 4 Omega, r = 0.78) with transthoracic shocks of 200, 300, and 360 J. In VF studies, the probability of defibrillation was closely fit by a sigmoidal dose response curve in the coronary sinus E field with an approximate threshold of 4.7 V/cm with 50% defibrillation success at 9.3 V/cm. CONCLUSIONS: The measured intracardiac E field variability within animals and at a specific site was small, exhibiting a median value of 5.1%, contrasted to median variabilities across animals of 5-11% suggesting the capacity of this measurement system to provide subject specific information on the distribution of E fields. The measured E field magnitudes across animals in the coronary sinus were linearly correlated with applied shock current with a very strong linear relation to effective shock voltage observed in vitro in a saline tank. When evaluated as a predictor of shock success, the observed values were consistent with previously reported critical fields. This technique may be of value in evaluating waveforms for transthoracic defibrillation as well as electrode size, placement, and composition. PMID- 17338712 TI - Ventricular pacing threshold variations in the young. AB - Ventricular Capture Management (VCM) is a Medtronic Kappa pacemakers (PM) feature that automatically measures pacing threshold through detection of the evoked response after a pacing stimulus. The aim of this study was to evaluate the range of variation of ventricular pacing threshold in pediatric patients with endocardial and epicardial pacing leads. Thirty-one patients (median age 6.5 years) were implanted with a Kappa 901 PM for atrioventricular block or sinus node dysfunction. Congenital heart defects (CHD) were present in 58% of patients. Ventricular leads were epicardial in 52% of patients. VCM was programmed to automatically measure threshold every 2 hours. In a median follow-up of 12 months, 27,110 threshold measurements, 72% of which were successful, have been taken in 94% of patients. Measurement success was 99% in the endocardial leads group (age at implantation 12 +/- 6 years) and 31% in epicardial leads (age 4 +/- 5 years) (P < 0.05). Main reasons for unsuccessful measurements were high heart rate and, in a patient with an endocardial lead, competition with intrinsic rhythm. Undersensing or oversensing of the evoked responses was not detected. In all successful VCM measurements, epicardial pacing and CHD contributed to stability of thresholds (multivariate analysis). Pacing threshold showed specific circadian patterns: higher thresholds were found between 00.00 and 06.00 a.m., but the variation was low, 0.03 +/- 0.01 V. In conclusion, children and young patients show stable ventricular thresholds, especially in presence of CHD, and epicardial leads are at least as stable as endocardial leads. Ventricular pacing threshold showed a circadian variability similar to that described in adults, that does not seem to influence VCM functioning and PM programming. PMID- 17338713 TI - Permanent and atrial-synchronized ventricular stimulation for clinically stable patients with normal or impaired left ventricular systolic function. AB - BACKGROUND: Ventricular desynchronization imposed by permanent dual-chamber ventricular pacing (VDD) may compromise ventricular function. METHODS: We investigated the impact of background VDD pacing on the right and left ventricular (LV) function on 129 clinically stable outpatients (mean age 69 +/- 10) implanted chronically with a dual-chamber pacemaker or an automatic defibrillator by using echocardiographic techniques including tissue doppler imaging (TDI) and color M-mode (CMM) examinations, and B-type natriuretic peptide (BNP) measurements. Patients were divided into two groups of normal (n = 65) or impaired (n = 64) LV systolic function (ejection fraction 63 +/- 6% and 38 +/- 10%, respectively) according to clinical and echocardiographic criteria. Each patient group included two subgroups on the basis of the underlying permanent and atrial-synchronized heart rhythm: either intrinsic ventricular activation (IVA) or VDD pacing. RESULTS: The BNP levels (mean, 95% CI) of patients with impaired LV systolic function were approximately threefold higher than those of patients with normal LV systolic function [189 (145-245) pg/mL vs 65 (50-85) pg/mL, P < 0.0001], but did not differ between subgroups of patients with IVA vs VDD pacing. By two-way analysis of variance and analysis of covariance, and after adjustment for age and gender, significant VDD pacing effects were found in terms of lower E/A ratio (P < 0.05) and increased LV end-systolic volume (P < 0.05). VDD pacing did not significantly affect the BNP levels and the LV filling pressures, as determined by the E/Ea and E/Vp ratios. CONCLUSIONS: Long-term VDD pacing may not be harmful in clinically stable patients with normal or moderately reduced LV systolic function. PMID- 17338714 TI - Transient overdrive pacing upon standing prevents orthostatic hypotension in elderly pacemaker patients with chronotropic incompetence. AB - BACKGROUND: Elderly pacemaker patients with chronotropic incompetence (CI) may experience orthostatic hypotension (OH) upon standing. The objective of this study was to determine whether a transient increase in heart rate (HR) by overdrive pacing upon standing prevents OH in elderly pacemaker patients. METHODS: We studied the effect of transient overdrive pacing upon standing in mitigating the drop in blood pressure (BP) in 62 pacemaker patients (77 +/- 6 years, 32 F) implanted with DDD pacemaker for sick sinus syndrome (n = 40) or atrioventricular block (n = 22). All patients underwent two standing procedures in random order: a control, with backup (60 bpm) pacing and another with overdrive DDD pacing (at 35 bpm above their baseline rate) for 2 minutes upon standing. Systolic (SBP) and diastolic blood pressure (DBP) and HR were measured while supine (baseline) and 1, 2, and 3 minutes after standing. OH was defined as a drop in SBP > or = 20 mmHg or DBP > or = 10 mmHg during standing. Chronotropic incompetence (CI) was defined as an absence of HR increase of > or = 10 bpm during standing. RESULTS: A total of 17 (27%) patients developed OH upon standing during backup pacing. Baseline clinical characteristics (age, sex, prevalence of diabetes, use of vasoactive medications, and sick sinus syndrome) were similar between patients with or without OH. In patients with or without OH, transient overdrive pacing upon standing increased HR and DBP as compared with baseline (P < 0.05). However, in patients with OH, transient overdrive pacing did not prevent decrease in SBP upon standing and avoided the development of OH in only 10/17 patients (59%). Among those patients with OH, 10/17 (59%) patients had CI. In OH patients with CI, transient overdrive pacing upon standing maintained SBP and DBP as compared to baseline and prevented OH in the majority of patients (80%). By contrast, transient overdrive pacing in OH patients without CI had no significant effect on the decrease in SBP upon standing and prevented OH in only 20% of patients. CONCLUSIONS: OH is common (27%) in the elderly pacemaker population. In a subgroup of these patients, CI may be responsible for the occurrence of OH, and OH can be prevented by transient overdrive pacing upon standing. PMID- 17338715 TI - The benefits of biventricular pacing in heart failure patients with narrow QRS, NYHA class II and right ventricular pacing. AB - OBJECTIVE: To identify subgroups of heart failure patients who might benefit from biventricular pacing. BACKGROUND: Cardiac resynchronization therapy (CRT) improves the quality of life, New York Heart Association (NYHA) functional class, and exercise capacity and decreases hospitalizations for heart failure for patients who have severe heart failure and a wide QRS. It is unclear if other populations of heart failure patients would benefit from CRT. METHODS: One hundred forty-four consecutive heart failure patients who underwent CRT and completed 3 months of follow-up were reviewed. Demographic, echocardiographic, electrocardiographic, and clinical outcome data were analyzed to assess the relationship of functional class and QRS duration before device implantation to postimplant outcomes. RESULTS: There were 20, 88, and 36 patients in NYHA functional class II, III, and IV, respectively. Thirty-four patients had right ventricular pacing and another 29 patients had a QRS duration < or = 150 ms. Patients who were in NYHA functional class II at baseline had significant improvement in left ventricular ejection fraction and indices of left ventricular remodeling after CRT. Similar significant findings were seen in the subgroup with right ventricular pacing at baseline after CRT. However, in the subgroup with a narrow QRS duration, there were no significant changes in the indices of left ventricular remodeling or in the NYHA functional class and there was a significant increase in the QRS duration. For the study cohort as a whole, an improvement in NYHA functional class after CRT correlated with a significant decrease in adverse clinical outcomes. CONCLUSIONS: Heart failure patients who were in NYHA functional class II and those with right ventricular pacing appeared to benefit from CRT. PMID- 17338716 TI - Venous obstruction after pacemaker implantation. AB - BACKGROUND: Central vein leads are known to predispose to venous obstruction. Although usually asymptomatic, obstruction may render electrode removal difficult. This study aimed at quantifying changes in venous calibers in a prospective fashion by intravenous contrast venography (ICV) before and after pacemaker (PM) or cardioverter-defibrillator implantation. METHODS: One hundred and fifty (mean age 67; 61% male) consecutive patients were enrolled, and followed for 6 months. A successful ICV was done at baseline prior to implantation and at 6-month follow-up in 136 (91%) patients. Minimum (D(min)) and maximum (D(max)) vessel diameters were obtained from both ICVs. A new stenosis was defined as a 50% diameter reduction in a venous segment when compared to baseline. We implanted a total of 230 electrodes: 47 (34.6%) single lead, 84 (61.8%) 2-lead, and 5 (3.7%) 3-lead systems. RESULTS: At baseline ICV, 10 patients (7%) were found to have venous anomalies, including 8 patients with obstructive lesions, 1 patient with a persistent left superior vena cava, and 1 patient with double axillary vein. At 6 months, a new obstructive venous lesion had developed in a total of 19 (14%) patients, none of whom exhibited any local symptoms. Of these patients 14 (10%) had a stenosis (mean D(min) 4.6 mm and diameter 38% of baseline), and 5 (3.6%) had a complete venous occlusion. In most cases the new stenosis developed in a location where the vessel was narrowest at baseline. Clinical predictors for the development of stenosis were atrial fibrillation at baseline and biventricular PM implantation. CONCLUSIONS: This is the first systematic study to quantify venous changes after PM or ICD implantation. Our study shows that venous anomalies rendering PM implantation difficult are not infrequent. The incidence of new venous obstruction was 14%. Atrial fibrillation and biventricular PM implantation were independent predictors of venous obstruction. PMID- 17338717 TI - Poor prognosis for patients with chronic kidney disease despite ICD therapy for the primary prevention of sudden death. AB - INTRODUCTION: Chronic kidney disease (CKD) has been independently associated with increased cardiovascular mortality. Little is known about the benefit of implantable cardioverter defibrillator (ICD) therapy for prevention of sudden death in this large, high-risk population. We sought to evaluate the impact of CKD on survival in patients who received an ICD for primary prevention of sudden death. METHODS AND RESULTS: In this retrospective study of patients who underwent ICD implantation for primary prevention of sudden death, patients were stratified by CKD, defined as serum creatinine > or = 2 mg/dL or dialysis use. Primary endpoint was mortality. CKD was identified in 35 of 229 patients (15.3%). There were 33 deaths during a follow-up period of 18.0 +/- 15.2 months: 17 of 35 CKD patients and 16 of 194 patients without CKD (48.6% vs 8.2%, P < 0.00001 by log rank). One-year survival for patients with and without CKD was 61.2% and 96.3%, respectively. Cox regression analysis controlling for age, sex, comorbidities, ejection fraction, and medications proved CKD to be the strongest independent predictor of death (hazard ratio 10.5; 95% confidence interval 4.8-23.1; P = 0.0001). This risk was dependant on severity of CKD; a 10 mL/min reduction in creatinine clearance was associated with a 55% increase in hazard of death (P < 0.0001). CONCLUSIONS: In patients receiving an ICD for primary prevention of sudden death, CKD significantly reduced long-term survival. This poor prognosis may limit the impact of primary prevention ICD therapy in this patient population. PMID- 17338718 TI - Laser lead extraction: predictors of success and complications. AB - BACKGROUND: Paralleling the rise in pacemaker and defibrillator implantations, lead extraction procedures are increasingly required. Concerns regarding failure and complications remain. METHODS AND RESULTS: A total of 200 lead extraction procedures were performed at the Montreal Heart Institute between September 2000 and August 2005. In 23 patients, all leads were removed by traction with a locking stylet. A total of 270 leads were extracted using a laser sheath system (Spectranectics, Colorado Springs, CO, USA) in 177 procedures involving 175 patients (74% male), age 62+/-16 years. Procedural indications were: infection 88 (50%), dysfunction 54 (30%), upgrade 21 (12%), and other 14 (8%). Overall, 241 leads (89%) were successfully extracted, 7 (3%) were partially extracted (< or = 4 cm retained), and 22 (8%) were non-extractable. In multivariate analyses, predictors of failed extraction were longer time from implant (OR 1.16 per year, P=0.0001) and history of hypertension (OR 5.2, P=0.0023). Acute complications occurred in 14 of 177 procedures (7.9%): 8 (4.5%) minor and 6 (3.4%) major, with one death. In multivariate analyses, the only predictor of acute complications was laser lead extraction from both right and left sides during the same procedure (OR 9.4, P = 0.0119). In addition, 3 of 10 patients with failed or partially extracted infected systems eventually required open chest explantation because of endocarditis. CONCLUSION: Most leads not amenable to manual traction may be successfully extracted by a percutaneous laser sheath system. While most complications are minor, major complications including death may occur. Older leads are at higher risk for failed extraction. Endocarditis may ensue if infected leads are incompletely removed. PMID- 17338719 TI - Rapid atrial pacing: a useful technique during slow pathway ablation. AB - BACKGROUND: Catheter ablation is the treatment of choice for atrioventricular nodal reentrant tachycardia (AVNRT) with a success rate of 95-98%. The appearance of junctional rhythm during radiofrequency (RF) application to the slow pathway has been consistently reported as a marker for the successful ablation of AVNRT. Ventriculoatrial (VA) conduction during junctional rhythm has been used by many as a surrogate marker of antegrade atrioventricular nodal (AVN) function. However, VA conduction may not be an accurate or consistent marker for antegrade AVN function and reliance on this marker may leave some patients at risk for antegrade AVN injury. OBJECTIVE: The purpose of this study is to describe a technique to ensure normal antegrade AVN function during junctional rhythm at the time of RF catheter ablation of the slow pathway. METHODS: Retrospective review of all patients less than 21 years old who underwent RF ablation for AVNRT at our institution from January 2002 to July 2005. During RF applications, immediately after junctional rhythm was demonstrated, RAP was performed to ensure normal antegrade AVN function. Postablation testing was performed to assess AVN function and tachycardia inducibility. RESULTS: Fifty-eight patients underwent RF ablation of AVNRT during the study period. The mean age +/- SD was 14 +/- 3 years (range: 5-20 years). The weight was 53 +/- 15 Kg (range: 19-89 Kg). The preablation Wenckebach cycle length was 397 +/- 99 msec (range: 260-700 msec). Fifty-four patients had inducible typical AVNRT, and four patients had atypical tachycardia. The mean tachycardia cycle length +/- SD was 323 +/- 62 msec (range: 200-500 msec). Patients underwent of 8 +/- 7 total RF applications (median: 7; range 1 to 34), for a total duration of 123 +/- 118 seconds (median: 78 sec, range: 20-473 sec). Junctional tachycardia was observed in 52 of 54 patients. RAP was initiated during junctional rhythm in all patients. No patient developed any degree of transient or permanent AVN block. Following ablation, the Wenckebach cycle length decreased to 364 +/- 65 msec (P < 0.01). Acutely successful RF catheter ablation was obtained in 56 of 58 patients (96%). CONCLUSION: Rapid atrial pacing during radiofrequency catheter ablation of the slow pathway is a safe alternative approach to ensure normal AVN function. PMID- 17338720 TI - Reinitiation of ventricular macroreentry within the His-Purkinje system by back up ventricular pacing - a mechanism of ventricular tachycardia storm. AB - BACKGROUND: We describe immediate reinitiation of macroreentry ventricular tachycardia (VT) involving the His-Purkinje system by ventricular pacing from the electrode of an implantable cardioverter defibrillator (ICD) as a mechanism of VT storm refractory to ICD therapy. METHODS AND RESULTS: Repetitive reinitiation of bundle branch reentry tachycardia (BBRT), interfascicular tachycardia, or both VTs by ventricular pacing was identified in four ICD patients presenting with VT storm or incessant VT. All patients had a pre-existing prolonged HV interval (75 +/- 9 ms) and left bundle branch block (LBBB) or bifascicular block during sinus rhythm. The VTs included BBRT with LBBB in three patients and interfascicular tachycardia with right bundle branch block (RBBB) and left anterior or left posterior fascicular block in two patients. The paced beats from the ICD electrode exhibited a LBBB pattern of depolarization in two patients and a RBBB contour in V1 and V2 with left axis deviation in two patients. The QRS complex during pacing from the ICD electrode closely resembled that of the recurrent VT in all four patients suggesting that the pacing site of the ICD electrode was in proximity to the myocardial exit site of the bundle fascicle used for antegrade conduction during the reinitiated VT. Ventricular pacing from the ICD electrode after termination of the VT apparently encountered the retrograde refractoriness of this bundle fascicle and allowed immediate re-propagation of the wavefront orthodromically along the VT circuit. BBRT was eliminated by ablation of the right bundle branch. Successful ablation of the interfascicular tachycardias was achieved by targeting (1) an abnormal potential of the distal left posterior Purkinje network or (2) a diastolic potential during VT in the midinferior left ventricular (LV) septum. CONCLUSIONS: Repetitive reinitiation of BBRT and interfascicular tachycardia by ventricular pacing from the ICD electrode should be considered as a mechanism of VT storm refractory to ICD therapy in patients with a pre-existing conduction delay within the His-Purkinje system. PMID- 17338721 TI - Use of noncontact mapping and saline-cooled ablation catheter for sinus node modification in medically refractory inappropriate sinus tachycardia. AB - BACKGROUND: Inappropriate sinus tachycardia (IST) is characterized by heart rate (HR) increase out of proportion to stress level. Radiofrequency (RF) modification of the sinus node (SN) is an accepted treatment modality for medically refractory IST. We describe a new technique using noncontact mapping and a saline irrigated catheter for SN modification. METHODS: Seven consecutive patients with medically refractory IST were referred for ablation. Intrinsic heart rate (IHR) was calculated with complete autonomic blockade by atropine and propranolol. Isoproterenol (ISO) 1 mcg/min was initiated and increased to 10 mcg/min. Site of earliest activation was tagged at each dose of ISO once stable HR was achieved. RF ablation to target site of earliest activation at peak HR on ISO 10 mcg/min was performed. With any change in P-wave morphology, activation was reassessed and the new site of earliest activation targeted. Endpoint was a decrease in HR and change in P-wave morphology in lead III and aVF. RESULTS: Five of seven patients had abnormal IHR. Mean number of RF lesions was 25 (10-52). All patients had either flattening of the P wave or development of negative P waves in leads III and aVF post RF associated with a decrease in HR of > or = 25% from baseline off ISO. A caudal shift of the site of early activation compared with baseline was observed. One patient who had a prior SN modification developed symptomatic intermittent junctional bradycardia and required an atrial pacemaker 2 weeks later. The other 6 patients in follow-up from 6 to 24 months had no further IST. CONCLUSIONS: Noncontact mapping using the described technique in conjunction with the saline-cooled ablation catheter for SN modification in the treatment of IST may provide effective HR control. PMID- 17338722 TI - Prediction of conversion from paroxysmal to permanent atrial fibrillation. AB - BACKGROUND: Paroxysmal atrial fibrillation (PAF) transits to permanent atrial fibrillation (PEAF). The current study was to determine whether a P wave triggered P wave signal averaged electrocardiogram (P-SAECG) and chemoreflexsensitivity (CHRS) are useful to predict a conversion to PEAF in patients with PAF. METHODS: The filtered P wave duration (FPD) and the root mean square voltage of the last 20 ms of the P wave (RMS 20) were measured by P-SAECG. The ratio between the difference of RR intervals in the ECG and venous pO2 before and after 5-minutes oxygen inhalation is measured (ms/mmHg) for the determination of CHRS. RESULTS: A total of 180 patients with PAF were enrolled and followed for a mean of 22.5 months. PEAF occurred in 38 patients (21%) and these patients had a significantly larger left atrial size (43.2 +/- 4.9 vs. 41.0 +/- 5.4 mm, P = 0.021), a significantly longer FPD (158.8 +/- 18.2 vs. 136.7 +/- 16.6 ms, P < 0.0001), and a significantly lower CHRS (1.96 +/- 0.99 vs. 2.44 +/- 1.19 ms/mmHg, P = 0.024) than patients with PAF. Patients with PEAF tended to have a lower RMS 20 (2.38 +/- 0.65 vs. 2.75 +/- 1.18 microV, P = 0.067) than patients with PAF. The chi(2) test showed that the combination of FPD > or = 145 ms, RMS 20 < or = 3.0 microV, left atrial size > or = 41 mm, and CHRS < or = 2.0 ms/mmHg had the best predictive power for PEAF. Patients who fulfilled these criteria had a 12 fold increased risk for a conversion from PAF to PEAF. CONCLUSIONS: Our results show that a P-SAECG, an analysis of CHRS, and left atrial enlargement are clinical predictors of a progression from PAF to PEAF. PMID- 17338723 TI - Supraventricular tachycardia with two VA intervals: what is the mechanism? PMID- 17338724 TI - Pacemaker tachycardia: is it pacemaker-mediated tachycardia or sinus tachycardia? PMID- 17338725 TI - Using the upper limit of vulnerability to assess defibrillation efficacy at implantation of ICDs. AB - The upper limit of vulnerability (ULV) is the weakest shock strength at or above which ventricular fibrillation (VF) is not induced when the shock is delivered during the vulnerable period. The ULV, a measurement made in regular rhythm, provides an estimate of the minimum shock strength required for reliable defibrillation that is as accurate or more accurate than the defibrillation threshold (DFT). The ULV hypothesis of defibrillation postulates a mechanistic relationship between the ULV-measured during regular rhythm-and the minimum shock strength that defibrillates reliably. Vulnerability testing can be applied at implantable cardioverter defibrillator (ICD) implant to confirm a clinically adequate defibrillation safety margin without inducing VF in 75%-95% of ICD recipients. Alternatively, the ULV provides an accurate patient-specific safety margin with a single fibrillation-defibrillation episode. Programming first ICD shocks based on patient-specific measurements of ULV rather than programming routinely to maximum output shortens charge time and may reduce the probability of syncope as ICDs age and charge times increase. Because the ULV is more reproducible than the DFT, it provides greater statistical power for clinical research with fewer episodes of VF. Limited evidence suggests that vulnerability testing is safer than conventional defibrillation testing. PMID- 17338726 TI - Endocardial ventricular pacing through a bioprosthetic tricuspid valve. AB - A patient with bioprosthetic tricuspid valve was treated with ventricular endocardial pacing using a new delivery system consisting of a steerable catheter and a 4.1 F bipolar, fixed-screw, steroid eluting lead. The functioning of the lead and bioprosthetic tricuspid valve was excellent during the following year. PMID- 17338727 TI - Extraction of the inner coil of a pacemaker lead slid into the pulmonary artery. AB - A patient required lead extraction for chronic draining sinus, due to abandoned leads. Preoperatively, the chest film showed a filament in the right pulmonary artery: it was the inner coil of an old atrial lead that, while remaining anchored to the auricle, slid outside the outer coil. By right subclavian approach, the old ventricular lead and the outer coil of the atrial lead were removed. Then, by right jugular approach, the freely floating end of the inner atrial coil was grasped by a pig-tail catheter, drawn back into the superior vena cava, exteriorized by a Lasso catheter, and finally extracted. PMID- 17338728 TI - Successful placement of left ventricular pacing lead despite coronary sinus perforation into the pericardial space with an obstructive flap. AB - Coronary sinus perforation is a relatively uncommon but much feared complication that may occur during the placement of left ventricular pacing lead. Coronary sinus perforation, especially in the presence of an obstructive flap, usually indicates the need to abandon the implantation attempt, as there are difficulties in crossing the obstructive flap as well as uncertainty of whether the lead is in the true lumen or into the pericardial space. We describe our experience in successfully placing the left ventricular lead safely despite the problems arising from these circumstances. PMID- 17338729 TI - Permanent cardiac pacing for severe pallid breath-holding spells. AB - We report the case of an infant affected by frequent episodes of loss of consciousness with the clinical features of pallid breath-holding attacks. Prolonged asystole, up to 26 seconds, was demonstrated by Holter monitoring. The patient was treated with permanent pacemaker implantation, followed by complete symptom resolution during a 26-month follow-up. PMID- 17338730 TI - Successful termination of atrial flutter by ibutilide during pregnancy. AB - Sustained atrial fibrillation and atrial flutter during pregnancy are uncommon arrhythmias that can significantly complicate normal prenatal care. Direct current external cardioversion is the current method of terminating these arrhythmias. In practice, however, this technique is sometimes considered undesirable by both physician and patients due to the need for deep sedation or anesthesia. In the present study, we describe the use of ibutilide to safely terminate symptomatic persistent atrial flutter in a patient during her 24th week of pregnancy. PMID- 17338731 TI - Reduction of pacemaker pressure symptoms using nonantigenic preserved human dermis grafts. AB - Skin pressure symptoms can occur in thin patients with pacemakers, with erosion through the skin surface a possibility. To correct this problem without device removal, two patients had nonantigenic preserved human dermis grafts placed over their pacemakers. This acellular nonantigenic human dermal substitute provided significant thickness over the devices and improvement in pressure symptoms. PMID- 17338733 TI - RE: Sauer et al, PACE 2006; 29: 1028-1030. PMID- 17338734 TI - Extent of low-grade dysplasia is a risk factor for the development of esophageal adenocarcinoma in Barrett's esophagus. AB - OBJECTIVES: Previous studies that evaluated extent of high-grade dysplasia (HGD) as a risk factor for esophageal adenocarcinoma (EA) in Barrett's esophagus (BE) were conflicting, and no prior study has evaluated extent of low-grade dysplasia (LGD) as a risk factor. The aim of this discovery study was to evaluate the hypothesis that extent of LGD and HGD are risk factors for progression to EA. METHODS: We evaluated baseline biopsies from 77 BE patients with dysplasia including 44 who progressed to EA and 33 who did not progress during follow-up. The total numbers of LGD and HGD crypts were determined separately by counting all crypts and the extent of LGD, HGD, and total dysplasia were correlated with EA outcome. RESULTS: Thirty-one and 46 patients had a maximum diagnosis of LGD and HGD, respectively. When the crypts were stratified by dysplasia grade, the mean number of LGD crypts per patient was borderline higher in progressors (93.9) compared with nonprogressors (41.2, P= 0.07), and the mean proportion of LGD crypts per patient was significantly higher in progressors (46.4%vs 26.0%, P= 0.037). Neither the mean number of HGD crypts per patient (P= 0.14) nor the mean proportion of HGD crypts per patient (P= 0.20) was significantly associated with EA outcome. CONCLUSIONS: The extent of LGD is a significant risk factor for the development of EA in BE in this study. Although the presence of HGD is significantly associated with a greater relative risk for development of EA, the extent of HGD was not an independent risk factor for progression. PMID- 17338735 TI - Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. AB - OBJECTIVES: After the withdrawal of some cyclooxygenase-2 (COX-2) selective inhibitors, traditional nonsteroidal anti-inflammatory drug (NSAID) use has increased, but without additional prevention strategies against upper gastrointestinal (GI) complications in many cases. Here, we report the effect of antisecretory drugs and nitrates on the risk of upper GI peptic ulcer bleeding (UGIB) associated with nonselective NSAIDs, aspirin, antiplatelet agents, and anticoagulants. METHODS: This case-control study matched 2,777 consecutive patients with UGIB (confirmed by endoscopy) with 5,532 controls (2:1). Adjusted relative risks (RR) of UGIB are reported. RESULTS: Proton pump inhibitors (PPIs) (RR 0.33, 95% confidence interval [CI] 0.27-0.39), H2-receptor antagonists (H2 RAs) (RR 0.65, 95% CI 0.50-0.85), and nitrates (RR 0.52, 95% CI 0.38-0.70) reduced UGIB risk. PPI use was associated with greater reductions among both traditional NSAID (RR 0.13, 95% CI 0.09-0.19 vs RR 0.30, 95% CI 0.17-0.53 with H2 RAs; RR 0.48, 95% CI 0.19-1.24 with nitrates) and low-dose aspirin users (RR 0.32, 95% CI 0.22-0.51 vs RR 0.40, 95% CI 0.19-0.73 with H2-RA; RR 0.69, 95% CI 0.36-1.04 with nitrates), and among patients taking clopidogrel (RR 0.19, 95% CI 0.07-0.49). For patients taking anticoagulants, use of nitrates, H2-RA, or PPIs was not associated with a significant effect on UGIB risk. CONCLUSION: Antisecretory agent or nitrate treatment is associated with reduced UGIB RR in patients taking NSAID or aspirin. Only PPI therapy was associated with a marked, consistent risk reduction among patients receiving all types of agents (including nonaspirin antiplatelet agents). Protection was not apparent in patients taking anticoagulants. PMID- 17338736 TI - Does cigarette smoking influence the phenotype of Crohn's disease? Analysis using the Montreal classification. AB - OBJECTIVES: The clinical subclassification of Crohn's disease by phenotype has recently been reevaluated. We have investigated the relationships between smoking habit, age at diagnosis, disease location, and progression to stricturing or penetrating complications using the Montreal classification. METHODS: 408 patients (157 male, median age 29.4 yr) were assessed. Data were collected on smoking habit, age at diagnosis, anatomical distribution, and disease behavior. Follow-up data were available on all patients (median 10 yr). RESULTS: At diagnosis, ex-smokers (N = 53) were older than nonsmokers (N = 177) or current smokers (N = 178, medians 43.2 vs 28.3 or 28.9 yr, respectively, P < 0.001). Disease location differed according to smoking habit at diagnosis (chi(2)= 24.1, P= 0.02) as current smokers had less colonic (L2) disease than nonsmokers or ex smokers (30%vs 45%, 50%, respectively). In univariate Kaplan-Meier survival analysis, smoking habit at diagnosis was not associated with time to development of stricturing disease, internal penetrating disease, perianal penetrating disease, or time to first surgery. Patients with isolated colonic (L2) disease were slower to develop strictures (P < 0.001) or internal penetrating disease (P= 0.001) and to require surgery (P < 0.001). Cox models with smoking habit as time dependent covariates showed that, relative to ileal (L1) location of disease, progression to stricturing disease was less rapid for patients with colonic (L2) disease (HR 0.140, P < 0.001), but not independently affected by smoking habit. Progression to surgery was also slower for colonic (L2) than ileal (L1) disease location (HR 0.273, P < 0.001), but was independent of smoking habit. CONCLUSIONS: Smoking habit was associated with age at diagnosis and disease location in Crohn's disease, while disease location was associated with the rate of development of stricturing complications and requirement for surgery. The pathogenic basis of these observations needs to be explained. PMID- 17338737 TI - Smoking habit and load influence age at diagnosis and disease extent in ulcerative colitis. AB - INTRODUCTION: Cigarette smoking affects susceptibility to ulcerative colitis (UC), but its effects on age at diagnosis, disease extent, and need for surgery are less well defined. We examined these parameters in a detailed retrospective analysis of a large cohort of well-characterized UC patients. METHODS: 499 UC patients (254 male, median age 34.3 yr) were studied. Data were collected on smoking habits, smoking load (pack-years), age at recruitment, age at diagnosis, surgery, and disease extent. Colonoscopic and histological data at both diagnosis and follow-up (median follow-up time 4.6 yr) were available on 349 patients. RESULTS: Ex-smokers were older at diagnosis than current or nonsmokers, (46.5 yr vs 31.1 or 29.4 yr, respectively, P < 0.001). Before diagnosis, ex-smokers had a higher smoking load than current smokers (13.0 vs 6.94 pack-years, P < 0.001). A Cox model for age at diagnosis, with smoking as a time-dependent covariate, showed that at any age, ex-smokers were significantly more likely to develop UC than current smokers (hazard ratio 1.8, 95% CI 1.41-2.44, P < 0.001). For current smokers at latest colonoscopy, those with extensive disease were the lightest smokers (median 0.320 pack-years), whereas those with healthy colons were the heaviest smokers (median 9.18 pack-years, P= 0.006). At 5 yr, regression of extensive disease was more frequent in current than ex-smokers or nonsmokers (30% current smokers vs 8% nonsmokers and 5% ex-smokers, chi(2)= 30.4, P < 0.001) but these differences were not maintained over a longer time period. CONCLUSIONS: Smoking habit influences the age at diagnosis and changes in disease extent in UC. Mechanisms are likely to be complex and require further investigation. PMID- 17338738 TI - Introduction of an OPCAB program aimed at total arterial grafting in a multidisciplinary setting: feasible and safe? AB - BACKGROUND: The feasibility and the results of the introduction of an off-pump coronary artery bypass (OPCAB) program aimed at total arterial revascularization in a multidisciplinary institution were analyzed. Uniform surgical and anesthetic protocols were established and applied throughout the study period. METHODS: From March 2003--when the first OPCAB procedure of the program was performed--to July 2004, the data related to all the coronary artery bypass grafting procedures (N = 408) were prospectively recorded. The program was divided into two stages: the purpose of the first stage was to perform OPCAB in more than 90% of the patients, and that of the second stage was to proceed toward total arterial revascularization. The patients were grouped into four periods (102 patients for each period). Comparisons were performed with analysis of variance test and chi square test where appropriate. RESULTS: For periods 1 to 4, the number of OPCAB procedures was 65/102 (64%), 82/102 (80%), 97/102 (95%), and 99/102 (97%), respectively (p < 0.001). The number of conversions did not vary significantly throughout the study (overall: 7/408, 1.7%), neither did the number of bypass/patient (overall: 3.05 +/- 0.86). The number of arterial graft/patient was 1.03 +/- 0.64, 1.01 +/- 0.4, 1.29 +/- 0.64, and 2.56 +/- 1, respectively (p < 0.001). During the last period, 81% (253/312) of the grafts were arterial. Overall mortality was 4.6% (19/408). For the OPCAB group, mortality was 2.9% (10/343) and perioperative myocardial infarction rate was 1.5% (5/343) with no statistically significant difference between the periods. CONCLUSIONS: With predefined standardized and coordinated protocols, an OPCAB program aimed at total arterial revascularization can be implemented rapidly and safely in a multidisciplinary setting. PMID- 17338740 TI - The hybrid total arch repair: brachiocephalic bypass and concomitant endovascular aortic arch stent graft placement. AB - BACKGROUND: Repair of aortic arch aneurysm is technically demanding, requiring complex circulatory management. Very large atherosclerotic saccular aneurysms of the arch are grave markers of extensive arch and brachiocephalic atheromatous disease and represent high surgical risks for perioperative neurologic complications. Operative morbidity and mortality may be prohibitive with traditional surgical intervention. We described our experience with a hybrid procedure for total arch repair with a brachiocephalic bypass with a trifurcated graft followed by concomitant placement of a stent graft in the arch. METHODS: Since June 2005, we have performed the hybrid total arch repair in eight patients. A retrospective review was performed to evaluate the new technique. RESULTS: The mean age of the patients was 67 years with a mean aneurysm size of 8 cm (range, 4.4 to 10 cm). Significant comorbidities included carotid stenosis, chronic renal insufficiency, peripheral vascular disease, hypertension, and coronary artery disease. Two patients had previous Abdominal aortic aneurysm (AAA) repairs. Three patients had previous sternotomy for type A dissection, ascending aortic aneurysm repair, and coronary artery bypass grafting. Transesophageal echocardiogram demonstrated grade IV or V atheromatous disease in the arch and ascending aorta. Stent grafts were deployed antegrade directly into the ascending aorta in three patients and retrograde from the femoral artery in five patients. Technical success with complete aneurysmal exclusion was achieved in all patients (100%). At a mean follow-up period of 11.7 months, there was no incidence of endoleak. There was one death resulting from a perioperative myocardial infarction (first patient). Documented perioperative neurologic events (stroke) occurred in two patients, with both patients demonstrating no residual deficit at the time of discharge. CONCLUSIONS: Saccular arch aneurysms can be technically treated by total arch repair with brachiocephalic bypass and concomitant aortic arch stent graft placement. Hybrid arch repair provides an alternative to patients otherwise considered prohibitively high risk for traditional open arch repair. PMID- 17338742 TI - Comparison of operative techniques in acute type A aortic dissection performing the distal anastomosis. AB - OBJECTIVE: The aim of our retrospective study was to evaluate early and midterm clinical outcomes of two surgical techniques: open anastomosis in deep hypothermic circulatory arrest (DHCA) compared to anastomosis with clamped aorta while continuing on extracorporeal circulation (CECC). METHODS: Between November 1997 and February 2002, 67 patients were operated for acute type A aortic dissection. Records of 35 patients with isolated replacement of the ascending aorta without intervention on the aortic arch were retrospectively reviewed. The influence of two techniques (DHCA n = 15, CECC n = 20) on clinical outcome and midterm follow up was investigated. RESULTS: There were no statistically significant differences in preoperative data. Female gender in the DHCA group was coincidentally more frequent. Intraoperative management did not result in different early clinical outcome. 30-day mortality was not statistically different. Mean follow up time was 20.7 +/- 11.1 months in the DHCA group and 28.7 +/- 14.3 months in the CECC group. One-year and 3-year survival estimates in DHCA group were 85%+/- 7% and 79%+/- 9%, respectively. In the CECC group similar survivals were 80%+/- 10% and 73%+/- 11%, respectively. No statistically significant differences between the two groups were obtained in early or midterm outcome. CONCLUSION: While there is no difference in clinical outcome in surgical treatment of acute type A aortic dissection with or without circulatory arrest, there are some practical technical advantages if the distal anastomosis is performed in an open manner. Probably the long-term outcome too is better with this anastomosis technique. PMID- 17338743 TI - Systematic reductive annuloplasty of the mitral and tricuspid valves in patients with end-stage ischemic dilated cardiomyopathy. AB - OBJECTIVE: Patients with ischemic dilated cardiomyopathy exhibit extensive remodeling of the left ventricle, annular dilation, and significant mitral and tricuspid regurgitation. These changes increase per operative morbidity and mortality, and emphasize patient candidacy for heart transplantation. The aim of this study is to show immediate and long-term results after reductive annuloplasty of double (mitral and tricuspid) orifices, performed at the time of coronary artery bypass grafting, as an alternative to heart transplantation. METHODS: There were 226 consecutive patients (205 males, 21 females) with ischemic dilated cardiomyopathy, mean ejection fraction below 30% [(26.6 +/- 3.1)%], and mean left ventricle end-diastolic internal diameter greater than 7.0 cm (7.3 +/- 0.3 cm). In addition to myocardial revascularization, Carpentier's mitral annuloplasty and posterior semicircular reductive annuloplasty were performed in 37 and 189 patients, respectively. In all 226 patients, a modified De Vega's tricuspid annuloplasty was performed. RESULTS: Postoperative 30-day mortality was 7.5% (17 patients). Survival rates after 5 and 10 years were (61.5 +/- 4.0)% and (38.05 +/- 8.0)%, respectively. CONCLUSION: Reductive annuloplasty of mitral and tricuspid orifices performed at the time of myocardial revascularization could be beneficial in selective patients with ischemic dilated cardiomyopathy. Results indicate that this method should not be recognized as a valve repair, but ventricular repair procedure also. PMID- 17338744 TI - Atrial fibrillation and plasma troponin I elevation after cardiac surgery: relation to inflammation-associated parameters. AB - BACKGROUND: Recent studies have demonstrated correlation between inflammation to plasma troponin (cTnI) levels elevation and atrial fibrillation (AF) in noncardiac surgery settings. The goal of this prospective study was to examine the relation between inflammation associated parameters (IAPs) to post cardiac surgery cTnI elevation and AF. METHODS: A single post CABG cTnI measurement was assessed in 156 consecutive patients. Clinical, operative and postoperative data, IAPs (hypophosphatemia, preoperative statin treatment, immediate postoperative fever, and prolonged mechanical ventilation) and in-hospital AF episodes were prospectively recorded. RESULTS: Mean cTnI level was 14.4 +/- 12.4 ng/mL. In the two in-hospital deaths (1.2%) cTnI concentration was less than 12 ng/mL. Cardiac troponin-I levels were significantly higher in patients not preoperatively treated with statins (21.6 +/- 4.1 vs. 13.3 +/- 0.9, p = 0.05), in patients who needed intraoperative cardioversion (16.7 +/- 2.2 vs. 12.2 +/- 0.9, p = 0.07), in patients with postoperative hypophosphatemia (16.9 +/- 10.0 vs. 11.1 +/- 13.7, p = 0.04), postoperative fever (18.6 +/- 3.0 vs. 13.7 +/- 1.0, p = 0.07) and postoperative respiratory complications (23.9 +/- 4.3 vs. 13.5 +/- 1.0, p = 0.04). Step-wise logistic regression analysis revealed the following parameters as independently associated with elevated cTnI levels: preoperative statin treatment (CI 95%-15.9; -1.7, p = 0.02), intraoperative ventricular arrhythmia (CI 95%-0.7; 13.8, p = 0.08), hypophosphatemia (CI 95% 0.9; 8.6, p = 0.02), postoperative fever (CI 95% 0.9; 11.0, p = 0.02), and postoperative respiratory complications (CI 95% 0.1; 0.5, p = 0.01). Of the 156 patients, 50 (32.1%) had postoperative AF. The first episode of AF occurred between postoperative day 1 and 6 (mean-day 2). Mean duration of AF was 21.8 +/- 8.1 hours. Postoperative AF was significantly associated with age above 75 (50% vs. 29.4%, p = 0.01), hypertension (37% vs. 18%, p = 0.02), preoperative calcium channel blockers treatment (44% vs. 26%, p = 0.02), furosemide treatment (58% vs. 30%, p = 0.05), and preoperative left atrial diameter above 40 mm (56% vs. 29%, p = 0.01). Postoperatively, AF was significantly associated with postoperative renal failure (70% vs. 29%, p = 0.01), respiratory complications (61% vs. 29%, p = 0.02), and prolonged hospital stay (OR 1.1; CI 1.0-1.3; p < 0.05). No association was found between troponin levels and postoperative AF. Multivariable analysis found only left atrial enlargement and prolonged hospital stay independently associated with AF. CONCLUSIONS: A significant correlation between clinical IAPs and cTnI plasma level elevation was found after cardiac surgery. There was no correlation between these parameters and postoperative AF, and there was no correlation between postoperative plasma cTnI levels and the occurrence of AF. Preoperative treatment with statins may be beneficial in reducing postoperative inflammatory response but further study has to be carried out. PMID- 17338745 TI - Spinal cord retrograde perfusion: review of the literature and experimental observations. AB - BACKGROUND: Spinal cord damage represents a devastating complication of thoracic and thoracoabdominal aortic surgery. Retrograde perfusion as an alternative route to protect the spinal cord has recently been investigated with controversial results. We reviewed the literature and analyzed additional experimental observations. METHODS: Ten juvenile pigs were divided into control and study groups (A and B, respectively). Through a lateral thoracotomy the distal aortic arch was cannulated and connected to a cardiotomy reservoir. All animals underwent 40-minute single cross-clamping of the proximal descending aorta while keeping proximal systolic arterial pressure above 100 mmHg. In group B, normothermic arterial blood was delivered retrogradely through the azygos vein, maintaining perfusion pressure within 25-30 mmHg. Animals were allowed to recover to perform a primary neurologic evaluation. RESULTS: Flaccid paraplegia was uniformly observed in group A. In group B, all animals showed mild-to-moderate voluntary hind limb movements on awakening (p = 0.007). Controls also showed urine incontinence short after cross-clamping, and this was not observed in group B (p = 0.008). A different veno-arterial oxygen step-down was observed in blood collected from the excluded aorta in the two groups (p < 0.001). CONCLUSIONS: Preliminary results indicate that controlled retrograde normothermic perfusion alone through the azygos system provides some degree of protection from spinal cord ischemia. Bladder dysfunction may represent a simple test to detect massive cord damage intraoperatively. Retrograde spinal cord perfusion warrants further investigation. PMID- 17338746 TI - Apoptosis and cardiopulmonary bypass. AB - AIM: The aim of this study was to ascertain the percentage of apoptotic myocytes in patients who underwent coronary artery bypass surgery. Apoptotic index (AI) obtained with in situ terminal deoxynucleotidyl transferase-labeled dUTP nick end labeling (TUNEL) method and Bak protein expression were compared. PATIENTS AND METHODS: Twenty consecutive patients who underwent coronary artery bypass surgery, myocardial samples from the right atrium were taken in three stages: before cannulation (the first sample group), after declamping (the second sample group), and 20 minutes after reperfusion (the third sample group). The percentage of apoptotic cells was determined by TUNEL method. Expression of Bak protein was immunohistochemically analyzed. Intermittent ischemia and moderate hypothermia were used as methods of myocardial management during surgery. A statistical analysis was performed by using the Friedman ANOVA analysis of variances, the Kendall coefficient of concordance and the Wilcoxon matched pair test. RESULTS: In the first sample group mean value of Bak expression was 2.61 +/- 2.18, compared with AI 5.38 +/- 3.58, after declamping (the second sample group) the mean value of Bak expression was 4.31 +/- 2.68 while AI was 7.63 +/- 4.38 and after 20 minutes of reperfusion in the third sample group mean value of Bak expression was 8.89 +/- 4.45, while AI was 15.6 +/- 8.45. When compared by using Wilcoxon matched pair test two methods significantly correlated, p > 0.0001. CONCLUSION: The positive correlation between AI obtained by TUNEL method and expression of Bak protein may suggest that apoptosis is activated mainly through mitochondrial activation pathway in ischemic reperfusion injury. The results suggest that ischemic reperfusion injury increases the AI in the right atrial tissue. If so, immunohistochemical expression of Bak protein could be used as a marker of myocardial ischemia induced injury. PMID- 17338747 TI - Beating-heart mitral valve reoperation in a patient with a permanent pacemaker. AB - A 60-year-old man with a history of a prior double-valve replacement (DVR) and permanent pacemaker implantation underwent mitral valve reoperation due to a paravalvular leak. Reoperation was performed on a beating heart (BH) on cardiopulmonary bypass, by perfusing the heart continuously with oxygenated noncardioplegic normothermic blood via the coronary sinus. We report the case of a patient who underwent mitral valve reoperation on a beating heart, 10 years after his first double-valve replacement and permanent pacemaker implantation. PMID- 17338748 TI - Reinforced edge-to-edge commissural closure with mitral valvuloplasty. AB - A variety of techniques has been used to repair prolapse of the commissure of the mitral valve. However, the application of these techniques may be technically challenging. A simple edge-to-edge suture approximation of anterior and posterior mitral leaflets is an effective way of restoring mitral valve competence. We use this technique with "spaghetti" for reinforcement, and annuloplasty for repair of the prolapse. We have recognized it to be a simple, durable, and reproducible technique for repair of prolapse of the mitral valve commissure. PMID- 17338749 TI - Open clip-free radial artery harvesting with the harmonic shears. AB - BACKGROUND: The Ultracision Harmonic Scalpel is associated with several advantages in radial artery (RA) harvesting. It allows fewer hemostatic clips to close the collateral branches, less thermal injury of the conduit, and reduced time of harvesting in comparison with the conventional RA harvesting technique with electrocautery and hemostatic clips. We recently started open RA harvesting with the harmonic shears (HSH). In this study, we aimed at evaluating the feasibility of this simplified ultrasonically activated harvesting technique, and report the results of RA harvesting with HSH. METHODS: The RA harvesting with HSH was performed in 20 patients operated on for myocardial revascularization from July 2004 to December 2005. RESULTS: The harvest of the RA was completed in little time, without any complication. Neither bleeding from the collateral branches nor spasm alongside the entire length of the RA was observed. No bleeding occurred from the muscles of the forearm. CONCLUSION: This technique of RA harvesting with HSH is impressive in terms of short time of harvest, complete absence of clips for the collateral branches, and no thermal injury of the conduit. PMID- 17338750 TI - Diagnostic and surgical approach to a descending thoracic aorta saccular aneurysm case. AB - Descending aorta saccular aneurysms are seen less than fusiform aneurysms. All symptomatic saccular aneurysms must be operated. In this study, we present a saccular aneurysm case developed at the descending aorta 1 year after a motor vehicle crash. Following an aorta-LAD saphenous vein graft anastomosis performed in beating heart, the aneurysm neck was closed with a Dacron patch under deep hypothermic circulatory arrest. All signs and symptoms removed dramatically after the operation. Regarding this case, we recommend that the surgical treatment must be performed in accordance with localization and specialties of aortic aneurysms. PMID- 17338751 TI - Orthotopic cardiac transplantation in a patient with pectus excavatum: approach via left anterior thoracotomy. AB - Severe pectus excavatum, although a rare condition, is likely to be encountered by large transplant centers. The main concerns for transplant centers are the associated cardiopulmonary abnormalities along with the technical details of the transplant. We describe our experience managing a patient with severe pectus excavatum with associated cardiorespiratory abnormalities. This case report demonstrates that orthotopic cardiac transplantation through a left anterior thoracotomy is a feasible method in patients with significant displacement of the heart into the left chest. PMID- 17338752 TI - Repeated paracentesis for treatment renal failure after heart transplantation in patient with ascites. AB - We report a case of orthotopic heart transplantation in a 42-year-old man who had cardiomyopathy with severe biventricular heart failure, ascites, and large umbilical hernia. He successfully received an orthotopic heart transplantation. After heart transplantation, renal failure was noted. Ascites and renal failure were successfully managed with repeated paracentesis. His cardiac and abdominal symptoms subsided gradually following transplantation. His umbilical hernia was repaired 55 days after the heart transplantation because of strangulation. In this case study, we report a patient with ascites who was treated for postoperative renal failure with repeated paracentesis. PMID- 17338753 TI - Management of concomitant coronary and bilateral carotid artery disease: a case report. AB - Patients with severe coexistent coronary and carotid artery stenosis represent a difficult and high-risk population. Herein we describe management of a patient with concomitant coronary artery and bilateral carotid artery disease. Firstly, left carotid artery stenting was done using a self-expandable monorail stent and a neurological protective device. Post-stent angiogram revealed satisfactory dilatation in the left carotid artery. Later, coronary artery bypass grafting to the four coronary arteries was done. Then right carotid endarterectomy was done. He had no neurological complication during or after any of the operation and he remains in good health since his last operation. We think the staged treatment, consisting of carotid artery stenting plus coronary artery bypass grafting plus carotid endarterectomy, in a patient with concomitant severe coronary artery and bilateral carotid artery disease is feasible, safe, and may be an alternative to combined coronary artery bypass grafting plus carotid endarterectomy. PMID- 17338754 TI - Transvenous cardioverter-defibrillator placement via a persistent left superior vena cava. AB - BACKGROUND: Persistent left superior vena cava (LSVC) is relatively uncommon. Due to its unanticipated location, large vessel injury is disproportionately common during transvenous intracardiac device implantation. AIM: The purposes of this report are: (1) to remind surgeons/physicians of this (LSVC) anatomic abnormality and, (2) to reassure surgeons/physicians that successful dysarrhythmia rescue is feasible with intracardiac defibrillator devices despite the obligate atypical anatomic positioning of the defibrillator electrodes. CASE SUMMARY: Catheter position in an LSVC appears fluoroscopically to traverse the left pleural space. The transvenous lead must negotiate a U-turn to enter the right ventricle. CONCLUSION: Despite the unconventional configuration of the intracardiac electrodes necessitated by the anatomy of a persistent LSVC, successful defibrillation is possible. PMID- 17338755 TI - Successful use of levosimendan in a patient during cardiopulmonary bypass. AB - Levosimendan (LS) is a novel calcium sensitizer drug that enhances cardiac contractility without increasing myocardial oxygen consumption, and induces vasodilatation. Positive inotropic support is routinely used for weaning from cardiopulmonary bypass circulation in patients with reduced left ventricular function. This case report represents the successful usage of LS for weaning from cardiopulmonary bypass circulation after coronary artery bypass surgery. Levosimendan infusion was started at the sixth hour of cardiopulmonary bypass circulation. There was a dramatic increase in cardiac output 20 minutes after LS infusion, and weaning from cardiopulmonary bypass circulation was achieved. We suggest that LS enhances cardiac performance during and after cardiopulmonary bypass, and can be useful for patients who are unable to be weaned from cardiopulmonary bypass. PMID- 17338756 TI - Hypoxemia complicating LVAD insertion: novel application of the Amplatzer PFO occlusion device. AB - We report a case of profound systemic hypoxemia complicating left ventricular assist device (LVAD) insertion due to right to left shunting through a patent foramen ovale (PFO) in association with a Chiari network. The patient was successfully managed with percutaneous closure of the interatrial defect using an Amplatzer PFO occlusion device and judicious reduction in LVAD flows. PMID- 17338757 TI - Right coronary revascularization using the right internal thoracic artery in situ with persisting side branches. AB - There is a controversy about flow steal when the internal thoracic artery is used, with its remnant branches, to revascularize the coronary system. We report a case of a 64-year-old man who was submitted to revascularization using an in situ right internal thoracic artery, with persisting side branches, to supply the right coronary system. Angiography, Doppler echocardiography, and echocardiography at rest and under stress were performed. We found no evidence of flow steal. PMID- 17338758 TI - Catheter entrapment during balloon angioplasty in patient with in-stent restenosis: an unusual complication and its surgical management. AB - Entrapment of coronary angioplasty hardware is one of the rare complications of percutaneous coronary artery interventions. We reported herein a case of 58-year old man with an entrapped balloon catheter and guidewire within the right coronary artery during the application of a conventional balloon angioplasty for in-stent restenosis. Surgical removal of the entrapped balloon catheter and guidewire was performed successfully with a coronary artery bypass grafting to the affected vessel. The application of the balloon angioplasty for in-stent restenosis requires every caution against such type of complications. PMID- 17338759 TI - Aneurysm of the right sinus of Valsalva after aortic valve replacement in Takayasu arteritis. AB - We herein report a case with an aneurysm of the right sinus of Valsalva, which developed 14 years after an aortic valve replacement (AVR) for aortic regurgitation caused by Takayasu arteritis. The aortic wall around the right coronary artery ostium showed calcification, as a result, the modified Bentall procedure and coronary artery bypass to the right coronary artery were successfully performed. A pathological study of the resected aortic sinus wall showed a disruption of the elastic fibers in the media, granuloma formation, and a marked proliferation of the collagen fibers in the adventitia, and these findings were compatible with Takayasu arteritis. The development of an aneurysm of the sinus of Valsalva late after AVR indicates the necessity of a close and lifelong follow-up for patients with Takayasu arteritis, especially focusing on the aortic root morphology. PMID- 17338760 TI - Impact of off-pump coronary artery bypass surgery on graft patency: current best available evidence. AB - For more than three decades cardiac surgeons have been used to perform delicate coronary anastomoses on cardiopulmonary bypass (CPB). However, the price of a still and bloodless field is ultimately paid by the patients in the form of sequelae of negative effects of CPB including blood trauma, activation of a series of inflammatory responses, nonpulsatile flow, and possible embolization of air or debris. In an attempt to avoid these deleterious effects of CPB, off-pump coronary artery bypass surgery (OPCAB) has been rediscovered and refined. Although abundant evidence is available to suggest that excellent results can be achieved when CPB is avoided, concerns have been raised about quality of anastomosis and graft patency rates after OPCAB surgery. We are currently practicing in an era of evidence-based medicine that mandates the prospective randomized controlled trial (RCT) as the most accurate tool for determining a treatment benefit compared with a control population. This review article attempts to evaluate the current best available evidence from RCTs on the impact of OPCAB surgery on graft patency. PMID- 17338761 TI - Improving patency of coronary conduits "valveless" veins and/or arterial grafts. AB - BACKGROUND: Veins used for coronary artery bypass operation have a well documented limited long-term patency. Internal thoracic artery (ITA) grafts have shown exceptional "durability." Assumptions were made that other arterial conduits have similar characteristics. AIM OF THE STUDY: The purpose of this article is to compare different conduits long-term patency including saphenous veins to other available arterial conduits: inferior epigastric artery (IE), right gastroepiploic artery (RGEA), and radial artery (RA). METHODS: Recent studies have shown that radial artery bypasses have lower patency rate than saphenous veins. Flow patterns, physiological flow characteristics are reviewed including native vessel disease and area of myocardium supplied. In the case of venous bypasses, the primary culprit of failure seemed to be the quality of the vein itself and the reverse venous valves in the conduit resulting in: (a) trapping-hypertension, (b) thrombosis, (c) turbulence, (d) intimal damage, (e) mismatching in size. RESULTS: Clinical follow-up of our patients up to 8 to 11 years (average 8.9 years) have proved the superior characteristics of the so called "good veins." In a retrospective study of 436 patients sequential, valveless veins patency was 88.6% versus 72% of reversed valvular segments (p < 0.01). Patients' survival seemed to be significantly improved if these veins were combined with ITA grafts. Patients' survival with one valveless limb HS + ITA was 78% versus HS + SV 52% (p < or = 0.0017) and HS + ITA versus HS + ITA + SV (p < 0.0057). CONCLUSION: Selective decision-making of the surgeon at the time of the operation is required to choose the best conduit to be able to perform the best operation with the best long-term result. PMID- 17338763 TI - Efficacy of adjuvant anterior left atrial ablation during intracardiac echocardiography-guided pulmonary vein antrum isolation for atrial fibrillation. AB - BACKGROUND: Recent data have shown that the septum and anterior left atrial (LA) wall may contain "rotor" sites required for AF maintenance. However, whether adding ablation of such sites to standard ICE-guided PVAI improves outcome is not well known. OBJECTIVE: To determine if adjuvant anterior LA ablation during PVAI improves the cure rate of paroxysmal and permanent AF. METHODS: One hundred AF patients (60 paroxysmal, 40 persistent/permanent) undergoing first-time PVAI were enrolled over three months to receive adjuvant anterior LA ablation (Group I). These patients were compared with 100 randomly selected, matched first-time PVAI controls from the preceding three months who did not receive adjuvant ablation (Group II). All 200 patients underwent ICE-guided PVAI during which all four PV antra and SVC were isolated. In group I, a decapolar lasso catheter was used to map the septum and anterior LA wall during AF (induced or spontaneous) for continuous high-frequency, fractionated electrograms (CFAE). Sites where CFAE were identified were ablated until the local EGM was eliminated. A complete anterior line of block was not a requisite endpoint. Patients were followed up for 12 months. Recurrence was assessed post-PVAI by symptoms, clinic visits, and Holter at 3, 6, and 12 months. Patients also wore rhythm transmitters for the first 3 months. Recurrence was any AF/AFL >1 min occurring >2 months post-PVAI. RESULTS: Patients (age 56 +/- 11 years, 37% female, EF 53%+/- 11%) did not differ in baseline characteristics between group I and II by design. Group I patients had longer procedure time (188 +/- 45 min vs 162 +/- 37 min) and RF duration (57 +/- 12 min vs 44 +/- 20 min) than group II (P < 0.05 for both). Overall recurrence occurred in 15/100 (15%) in group I and 20/100 (20%) in group II (P = 0.054). Success rates did not differ for paroxysmal patients between group I and II (87% vs 85%, respectively). However, for persistent/permanent patients, group I had a higher success rate compared with group II (82% vs 72%, P = 0.047). CONCLUSIONS: Adjuvant anterior LA ablation does not appear to impact procedural outcome in patients with paroxysmal AF but may offer benefit to patients with persistent/permanent AF. PMID- 17338764 TI - Continuous nonfluoroscopic localization of the esophagus during radiofrequency catheter ablation of atrial fibrillation. AB - INTRODUCTION: Atrial-esophageal fistula formation is a dreaded complication of radiofrequency catheter ablation for atrial fibrillation. Esophageal localization is of potential value in avoiding lesion placement where the left atrium is juxtaposed to the esophagus. METHODS AND RESULTS: Twenty-seven patients underwent 33 pulmonary vein encirclement procedures. All the patients received general anesthesia with inhalational agents and either a fenestrated laryngeal mask airway or an endotracheal tube. A diagnostic electrophysiologic catheter was inserted into the esophagus, and a virtual esophageal tube was created using an electroanatomic mapping system. In all cases, the catheter was placed without difficulty and satisfactory virtual esophageal images were created. The catheter remained in the esophagus until the end of each ablation procedure. Esophageal catheter location during and after the ablation was compared with the initial location. Areas of close proximity between the left atrium and esophagus were easily identified. Change in esophageal location was not observed. Identification of esophageal proximity to the pulmonary veins allowed for identification of high risk cases. In such cases, the planned procedure was modified to avoid esophageal injury (12 of 27 patients). CONCLUSIONS: (1) Real-time localization of esophageal position using a nonfluoroscopic mapping system during atrial fibrillation ablation is safe, practical, and straightforward. (2) Among patients who receive general anesthesia, esophageal position appears to be static, suggesting that one initial virtual image is sufficient for the duration of an ablation procedure. PMID- 17338765 TI - A novel algorithm for determining endocardial VT exit site from 12-lead surface ECG characteristics in human, infarct-related ventricular tachycardia. AB - INTRODUCTION: Characteristics of the 12-lead ECG during VT are used to guide initial placement of mapping catheters in endocardial ventricular tachycardia (VT) ablation. Previously constructed algorithms for guidance in human infarct related VT are limited to patients known to have anterior or inferior infarcts only. We hypothesized that 12-lead ECG characteristics could be used to determine VT exit site in patients with all types of infarction of unknown location. METHODS AND RESULTS: From noncontact activation maps of 121 LV VT in 51 patients undergoing catheter ablation, VT exit sites were determined and correlated with ECG characteristics according to bundle branch block configuration, limb lead polarity and patterns of precordial R-wave transition. Eight ECG patterns were identified that accounted for 71% of all VT and gave a positive predictive value (PPV) > or =70% using the first two criteria. No correlation was found with patterns of R-wave transition. Using these criteria an algorithm was developed, which was then applied prospectively and blinded to a further 17 VT in 11 patients. Of the 15 VT (88%) to which the algorithm predicted an exit site location (with a PPV > or =70%), 14 VT (93%) were correctly predicted by the algorithm. CONCLUSION: This algorithm can be used to predict endocardial LV VT exit site location in patients undergoing catheter ablation of VT without knowledge of or reference to infarct location, and can be applied to patients with posterior and/or multiple sites of infarction. PMID- 17338766 TI - Obesity as a risk factor for sustained ventricular tachyarrhythmias in MADIT II patients. AB - BACKGROUND: Obesity, as defined by body mass index > or =30 kg/m(2), has been shown to be a risk factor for cardiovascular disease. However, data on the relationship between body mass index (BMI) and the risk of ventricular arrhythmias and sudden cardiac death are limited. The aim of this study was to evaluate the risk of ventricular tachyarrhythmias and sudden death by BMI in patients after myocardial infarction with severe left ventricular dysfunction. METHODS: The risk of appropriate defibrillator therapy for ventricular tachycardia or ventricular fibrillation (VT/VF) by BMI status was analyzed in 476 nondiabetic patients with left ventricular dysfunction who received an implantable cardioverter defibrillator (ICD) in the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT II). RESULTS: Mean BMI was 27 +/- 5 kg/m(2). Obese patients comprised 25% of the study population. After 2 years of follow-up, the cumulative rates of appropriate ICD therapy for VT/VF were 39% in obese and 24% in nonobese patients, respectively (P = 0.014). In multivariate analysis, there was a significant 64% increase in the risk for appropriate ICD therapy among obese patients as compared with nonobese patients, which was attributed mainly to an 86% increase in the risk of appropriate ICD shocks (P = 0.006). Consistent with these results, the risk of the combined endpoint of appropriate VT/VF therapy or sudden cardiac death (SCD) was also significantly increased among obese patients (Hazard Ratio 1.59; P = 0.01). CONCLUSIONS: Our findings suggest that in nondiabetic patients with ischemic left ventricular dysfunction, a BMI > or =30 kg/m(2) is an independent risk factor for ventricular tachyarrhythmias. PMID- 17338767 TI - Acute evaluation of programmer-guided AV/PV and VV delay optimization comparing an IEGM method and echocardiogram for cardiac resynchronization therapy in heart failure patients and dual-chamber ICD implants. AB - INTRODUCTION: Intracardiac delay optimization of biventricular and dual-chamber pacing devices currently relies on time-consuming echocardiographic measurements. A novel intracardiac electrogram (IEGM) method for atrioventricular (AV/PV) and interventricular (VV) delay optimization was developed, which can be performed during routine device follow-up. METHODS AND RESULTS: In this prospective, nonrandomized, multi-center trial, patients previously implanted with St. Jude Medical cardiac resynchronization therapy defibrillator (CRT-D) devices or dual chamber implantable cardioverter defibrillators (ICDs) underwent standard AV/PV and/or VV delay optimization guided by Doppler echocardiogram measurements of the maximum aortic velocity time integral (aortic VTI). Aortic VTI measurements applying the IEGM method recommended delays were then obtained in all patients. Fifty-eight patients (age: 68 +/- 11 years; 81% male; 74% ischemic) and 57 patients (age: 71 +/- 10 years; 74% male; 71% ischemic) were enrolled for AV/PV and VV delay evaluation, respectively. An independent core lab determined the maximum aortic VTIs. Data analysis of the AV, PV, and VV delays demonstrated the concordance correlation coefficient (CCC) between the standard method aortic VTI values and the IEGM method aortic VTI values was 97.5%, 96.1%, and 96.6%, respectively. All analyses demonstrated that the CCC > 90% (P < 0.05). CONCLUSION: The automated programmer-based IEGM method provides a reliable and simpler alternative to standard techniques for the optimization of AV/PV and VV delay settings in patients with CRT-D devices and dual-chamber ICDs. PMID- 17338768 TI - Action potential and QT prolongation not sufficient to cause Torsade de Pointes: role of action potential triangulation. PMID- 17338769 TI - A novel mesh electrode catheter for mapping and radiofrequency delivery at the left atrium-pulmonary vein junction: a single-catheter approach to pulmonary vein antrum isolation. AB - BACKGROUND: Electrical isolation of pulmonary veins (PV) by radiofrequency (RF) ablation is often performed in patients with atrial fibrillation (AF). Current catheter technology usually requires the use of a multielectrode catheter for mapping in addition to the ablation catheter. PURPOSE: We evaluated the feasibility and safety of using a single, expandable electrode catheter (MESH) to map and to electrically isolate the PV. METHODS AND RESULTS: Nineteen closed chest mongrel dogs, weighing 23-35 kg, were studied under general anesthesia. Intracardiac echocardiography (ICE) was used to guide transseptal puncture and to assess PV dimensions and contact of the MESH with PV ostia. ICE and angiography of RSPV were obtained before and after ablation, and prior to sacrifice at 7-99 days. An 11.5 Fr steerable MESH was advanced and deployed at the ostium of the RSPV. Recordings were obtained via the 36 electrodes comprising the MESH. For circumferential ablation, RF current was delivered at a target temperature of 62 65 degrees C (4 thermocouples) and maximum power of 70-100 W for 180 to 300 seconds. Each animal received 1-4 RF applications. Entrance conduction block was obtained in 13/19 treated RSPVs. Pathological examination confirmed circumferential and transmural lesions in 13 of 19 RSPV. LA mural thrombus was present in 3 animals. There was no significant PV stenosis. CONCLUSION: Based on this canine model, a new expandable MESH catheter may safely be used for mapping and for PV antrum isolation. This approach may decrease procedure time without compromising success rate in patients undergoing AF ablation. PMID- 17338770 TI - Successful catheter ablation of two types of ventricular tachycardias triggered by cardiac resynchronization therapy: a case report. AB - We report a case of a patient with nonischemic dilated cardiomyopathy and implantable cardioverter-defibrillator, in whom an upgrade to biventricular pacing triggered multiple episodes of ventricular tachycardias (VTs) of two morphologies. First VT presented as repetitive nonsustained arrhythmia of the same morphology as isolated ectopic beats, suggesting its focal origin. Second VT was reentrant and was triggered by the former ectopy, leading to a therapy from the device. Electroanatomical mapping of the left ventricle revealed relatively small low voltage area in the left ventricular outflow tract and identified both an arrhythmogenic focus as well as critical isthmus for reentrant VT. Radiofrequency catheter ablation successfully abolished both VTs. After the procedure, biventricular pacing was continued without any recurrences during a period of 24 months. The report emphasizes the role of catheter ablation in management of VTs triggered by cardiac resynchronization therapy. PMID- 17338771 TI - Wide QRS complex tachycardia with an unusual mode of tachycardia initiation. PMID- 17338772 TI - Compression of the posterior left atrium by a nonaneurysmal descending thoracic aorta in a patient undergoing pulmonary vein isolation procedure for atrial fibrillation. PMID- 17338773 TI - Paroxysmal atrioventricular block following a ventricular premature beat. PMID- 17338774 TI - Evaluation of the normal values for signal-averaged electrocardiogram. PMID- 17338775 TI - Ionic basis of pharmacological therapy in Brugada syndrome. AB - An implantable cardioverter-defibrillator is considered the only effective therapy to terminate ventricular arrhythmias in symptomatic patients with Brugada syndrome. However, it does not prevent future arrhythmic episodes. Only antiarrhythmic drug therapy can prevent them. There have been several reports of a beneficial effect of oral quinidine in both asymptomatic and symptomatic patients. Other possible beneficial oral agents could be I(to) blockers. Intravenous isoproterenol has been reported to be especially useful in abolishing arrhythmic storms in emergency situations. Also, isolated case reports on the usefulness of cilostazol, sotalol, and mexiletine have been described. The present article reviews the mechanisms by which these drugs may act and their possible role in the pharmacotherapy of this disease. PMID- 17338776 TI - Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. AB - The prevalence of hepatitis B virus (HBV) infection in patients with haematological malignancies is increased compared with the general population worldwide. HBV reactivation is common following chemotherapy and is associated with a high mortality despite prompt anti-viral treatment. HBV reactivation may necessitate interruption of chemotherapy with adverse prognostic consequences for the haematological disease. Chemotherapy-induced immune suppression may lead to increased HBV replication. Immune reconstitution within the weeks and months following recovery from chemotherapy may be associated with a flare of hepatitis B manifested by hepatocellular injury. Risk factors associated with HBV reactivation include detectable hepatitis B surface antigen (HBsAg), HBV DNA, Hepatitis B e (HBeAg) antigen, antibodies to hepatitis B core antigen (anti-HBc), treatment with corticosteroids, young age and male gender. Lamivudine is effective during HBV reactivation due to immune suppression. Clinical trials have demonstrated that pre-emptive antiviral treatment with lamivudine is superior to deferred treatment. Current recommendations emphasise screening for HBV infection in all haematology patients, particularly prior to chemotherapy. Patients who are HBsAg positive or HBV DNA positive should receive pre-emptive treatment with lamivudine before chemotherapy. The duration of lamivudine treatment may be prolonged commensurate with the degree of immunosuppression. HBV naive patients should be immunised against hepatitis B, as should haematopoietic stem cell donors. In summary, overt and occult HBV pose a serious, but preventable, threat. Pre-treatment screening of patients at risk should be practiced diligently by all clinicians that treat patients with malignancies. PMID- 17338778 TI - Non pharmacological management of asthma: little change in the evidence base over 5 yr. PMID- 17338777 TI - Biomolecular characterisation of leucocytes by infrared spectroscopy. AB - Over the last 15 years, infrared (IR) spectroscopy has developed into a novel and powerful biomedical tool that has multiple applications in the field of haematology. By revealing subtle alterations in both the conformation and concentration of key macromolecules, such as DNA, protein and lipids, IR spectroscopy has been employed to investigate multiple aspects of leucocyte physiology. IR spectroscopy has been used, for example, to diagnose and prognose leukaemia; to characterise differentiation and apoptotic processes; to predict drug sensitivity and resistance in leukaemic patients undergoing chemotherapy; to monitor the response of leucocytes to chemotherapy and to perform human leucocyte antigen matching for bone marrow transplant patients. Such studies have provided insight into pathogenic mechanisms underlying specific leucocyte disorders, especially leukaemia. While it is likely to be some considerable time before IR spectroscopy is sufficiently developed to displace the established technologies, IR spectroscopy has the potential to become a valuable analytic tool in basic and clinical haematology. PMID- 17338780 TI - Age-related difference in immune responses to respiratory syncytial virus infection in young children. AB - There have been longitudinal studies of the developmental change of the immune system during the first year of life. The aim of this study was to investigate if there is any age-related difference in cytokine responses to respiratory syncytial virus (RSV) infection between the patients under 6 months of age and the patients over 12 months of age compared with age-matched controls. Forty-five children < or =24 months of age who were admitted with acute RSV bronchiolitis were enrolled. The patients were divided into two groups: the infants < or =6 months old and the young children > or =12 months old. Immune response to RSV infection was determined by measuring the serum concentrations of cytokines and compared with age-matched controls. Serum samples were obtained on admission and analyzed for interferon (IFN)-gamma, interleukins (IL)-10, -13, and -4 using ELISA. Comparing the cytokine levels of two control groups, both IFN-gamma and IL 13 were lower in the children > or =12 months of age than in the infants < or =6 months of age. IL-10 and IL-4 showed no significant changes with age. Comparing with age-matched controls, IFN-gamma levels were significantly higher in RSV group > or =12 months of age, but showed a tendency toward lower levels in RSV group < or =6 months of age. Both IL-10 and IL-13 levels were significantly higher in RSV group > or =12 months of age, but showed no significant difference in RSV group < or =6 months of age. Our study demonstrated a significant age related difference in immune response to RSV infection during early life. It suggests that the developmental changes in cytokine responses to RSV infection may be considered in the control of RSV bronchiolitis in young children. PMID- 17338781 TI - Nasal lavage leukotrienes in infants with RSV bronchiolitis. AB - Respiratory syncytial virus (RSV) bronchiolitis is a very common infection in infants and, after the acute phase, a number of patients develop a reactive airway disease that lasts for years. Although the pathogenesis of the lung damage after RSV bronchiolitis is still largely unknown, previous studies suggest that leukotrienes may play an active part in it. The aim of this study was to measure leukotriene levels in the nasal lavage fluid (NLF) collected in infants during RSV bronchiolitis and 1 month later. Cysteinyl leukotrienes (Cys-LTs) and leukotriene B(4) (LTB(4)) were measured in the NLF of 22 infants with their first episode of RSV bronchiolitis and 16 healthy infants. A second NLF sample was collected to measure leukotriene levels 1 month after the acute disease. NLF Cys LT levels were significantly higher in infants with RSV bronchiolitis than in healthy controls [950 pg/ml (285.5-2155.9) vs. 110.5 pg/ml (66.5-451.3), p = 0.01], and they remained so a month after the acute infection (p = 0.02). A subanalysis showed no difference in Cys-LTs concentrations, either between bronchiolitis infants with and without a family history of atopy, or between those with and without passive exposure to cigarette smoke. No significant difference was found between the LTB(4) levels measured in the bronchiolitis cases and the control children. Cys-LTs are significantly increased in the NLF of infants with acute RSV bronchiolitis, and remain so at 1-month follow-up, suggesting a possible role of these eicosanoids in the pathogenesis of the disease. PMID- 17338782 TI - Consumption of asthma medication after RS-virus epidemic--a population based survey. AB - It has been suggested that a respiratory syncytial virus (RSV) infection in infancy increases the likelihood of development of asthma in childhood. The RSV epidemics have a special 2-yr pattern in Finland and this allows the evaluation of the association of RSV and asthma by epidemiological means. We evaluated whether being 0-6 months of age during an RSV epidemic has an impact on the use of asthma medication later in the childhood. The consumption of asthma medication at the age of 3-16 yr and the number of those entitled to special reimbursement for asthma medication were identified for a total of 637,922 children. These subjects were grouped in cohorts according to whether they had been aged 0-6 months (exposed) or not (unexposed) during an RSV epidemic. The means of the proportions taking asthma medication and of those receiving reimbursement were calculated for each cohort. The means of the proportions in the unexposed vs. exposed cohorts were 20.5% vs. 20.3% for consumption and 4.8% vs. 4.9% for reimbursement. These differences were insignificant. In conclusion exposure to a RSV epidemic in infancy does not increase the consumption of asthma medicines at the population level. PMID- 17338783 TI - Bacterial colonization in respiratory secretions from acute and recurrent wheezing infants and children. AB - Lower respiratory tract infection in childhood often results in airway obstruction, characterized by wheezing. However, contribution of bacterial colonization to the wheezy state in children remains unclear. Wheezing and non wheezing children requiring hospitalization were classified into three groups: (i) wheezing children having a past history of recurrent wheezing; (ii) wheezing children without such history; and (iii) non-wheezing children as control subjects. Respiratory secretions as sputum were analyzed microscopically, and cultured. Cultured pathogenic bacterial species in sputum were categorized into two subgroups according to their amounts, i.e., dominant and non-dominant amounts of colonies. Incidence of bacterial colonization and wheezing were assessed. Hospitalized children were mainly 1- to 2-yr old, and rapidly decreased in number for older ages. Children in the three groups belonged to different clinical entities. Children in the recurrent wheezing group were highly sensitized to mite allergens, and still required hospitalization after 2 yr of age. Incidence of bacterial colonization was similar between the three groups. Dominant and non dominant amounts of bacterial colonization were 170/997 (17.1%) and 170/997 (17.1%), respectively, in the recurrent wheezing group; 28/146 (19.2%) and 35/146 (24.0%), respectively, in the acute wheezing group; and 15/56 (26.8%) and 7/56 (12.5%), respectively, in the non-wheezing group. Regardless of the presence of wheezing, bacterial colonization commonly occurred at a young age in the three groups. In recurrent wheezing children, boys (122/611, 20.0%) carried non dominant amounts of bacteria more frequently than girls (48/386, 12.4%) (p < 0.01). Boys showed predominant wheezing and susceptibility to bacterial colonization. Assessment of bacterial colonization allowed us to characterize asthma onset and outgrowth in childhood. PMID- 17338784 TI - The effects of maternal smoking on early mucosal immunity and sensitization at 12 months of age. AB - With the dramatic rise in asthma and respiratory disease, there is an urgent need to determine the effects of common environmental exposures on early immune development. In this study, we examined the effects of maternal smoking as a major adverse exposure in early life, on mucosal immune function and allergen sensitization in the first year of life. A cohort of 60 smokers and 62 non smokers was recruited in pregnancy, and followed prospectively at 3 and 12 months of age for saliva collection [for immunoglobulin (Ig) A measurements], urine collection (for cotinine levels) and clinical assessments (for allergy and infection history). Allergen skin-prick tests were also performed at 12 months of age. Specific IgA to common colonizing bacteria was measured on saliva samples, including pneumococcal polysaccharide (PS) serotype 14 and non-typeable Haemophilus influenza (NTHI) outer membrane protein 6 (OMP6). Eighty-two mothers and their infants completed the 12-month follow-up period--56 in the maternal non smoking group and 26 in the maternal smoking group. Maternal smoking was associated with significantly higher total infant salivary IgA at 12 months of age (p = 0.026), and more chronic upper respiratory tract symptoms (p = 0.012). However, there were no differences in the level of specific IgA antibodies to common colonizing bacteria (pneumococcal PS serotype 14 and NTHI OMP6). In general, the IgA levels at 12 months were higher in children who had more chest infections in the first year (Kendall's tau b, 0.282; p = 0.003). There was also a trend of lower respiratory tract symptoms (wheeze) (p = 0.142) in infants of smokers. There were no effects of maternal smoking on the rates of allergen sensitization, atopic dermatitis and food allergy at 12 months of age. In conclusion, maternal smoking did not inhibit the production of anti-microbial IgA, suggesting that other factors are responsible for the increased susceptibility to infection in these infants. The increased mucosal inflammation in these children was not associated with effects on early allergy propensity. PMID- 17338785 TI - A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma. AB - A number of studies have suggested that intake of paracetamol during pregnancy and during the first months of life is associated with an increased risk of childhood asthma. We aimed to determine the association between paracetamol usage during pregnancy and the first 6 months of life, and childhood allergy (i.e. positive skin prick tests), allergic asthma, and asthma, using a matched patient sibling study comparing patients with allergic asthma with their healthy siblings without any symptoms of allergic diseases. Allergy in patients and their siblings was determined by skin prick tests. Children having at least one positive skin prick test were considered to be allergic. Intake of paracetamol was assessed by standardized, interviewer-administered, questionnaire. Nineteen pairs of allergic asthma patients vs. non-allergic siblings were compared to determine the risk factors for allergic asthma, while 15 pairs of allergic asthma patients vs. allergic siblings were compared to determine the risk factors for asthma. Moreover, 33 pairs of allergic asthma patients vs. non-asthmatic siblings (with and without allergy) were compared to determine the risk factors for asthma. In addition, 17 allergic siblings (without asthma) were compared with 19 non allergic siblings (without asthma) to determine the risk factors for allergy. Usage of paracetamol during pregnancy was associated with allergic asthma (p = 0.03). Furthermore, usage of paracetamol between birth and 6 months of age, and between 4 and 6 months of age, was also found to be associated with non-allergic asthma (p = 0.008 and p = 0.03 respectively). Usage of paracetamol during pregnancy and during the early months of life may play a role in the development of allergic and non-allergic asthma in children. However, due to obvious ethical reasons, direct evidence for this association (i.e. a double-blind, prospective study) is not available. PMID- 17338786 TI - Comparison of clinically diagnosed asthma with parental assessment of children's asthma in a questionnaire. AB - Epidemiological evaluations of the prevalence of asthma are usually based on written questionnaires (WQs) in combination with validation by clinical investigation. In the present investigation, we compared parental assessment of asthma among their preschool children in response to a WQ with the corresponding medical records in the same region. An International Study of Asthma and Allergies in Childhood (ISAAC)-based WQ was answered by 75% of the parents of 6295 children aged 1-6 yr. Clinically diagnosed asthma, recorded in connection with admissions to the hospital or a visit to any of the outpatient clinics in the same region, were analysed in parallel. Finally, a complementary WQ was sent to the parents of children identified as asthmatic by either or both of this approaches. In response to the WQ 5.9% were claimed to suffer from asthma diagnosed by a doctor. According to the medical records, the prevalence of clinically diagnosed asthma was 4.9%. The estimated prevalence among children requiring treatment for their asthma was 4.4%. The sensitivity of the WQ was 77%, the specificity 97.5%. In the 1-2 yr age group the sensitivity was only 22%. This WQ was able to identify 54% of the children with a medical record of asthma. Forty percent of the children claimed by their parents to be asthmatic had no medical record of asthma. An ISAAC-based parentally completed WQ provided an acceptable estimation of the prevalence of asthma in children 2-6 yr of age, although only half of the individual patients identified in this manner are the same as those identified clinically. PMID- 17338787 TI - Environmental and socio-demographic factors associated to asthma in adolescents in Rio de Janeiro, Brazil. AB - Although asthma is of frequent occurrence, little is known about the factors associated with this disease in Brazil. We studied the association between asthma, environmental and socio-demographic factors in adolescents in Nova lguacu, Rio de Janeiro State. Cross-sectional study using the questionnaires about asthma and environmental factors from the International Study of Asthma and Allergies in Childhood (ISAAC). We performed bivariate analyses between asthma and the factors studied using prevalence ratio (PR), confidence intervals of 95% (95% Cl) and Chi-squared test. Factors associated to asthma in a bivariate analysis were studied using logistic regression and odds ratio (OR). We included 3,033 students, aged 13-14 yrs, selected from 37 schools. The prevalence of asthma was 13.1%. Being female (OR = 1.40; 95%Cl:1.11-1.77), the presence of a mother who smokes (OR = 1.32; 95%Cl:1.04-1.66), a cat in the domicile (OR = 1.32; 95%Cl:1.04-1.69), being the firstborn (OR = 1.34; 95%Cl:1.07-1.68), frequent use of paracetamol (OR = 1.45; 95%Cl: 1.15-1.84), the presence of rhinitis (OR = 5.15; 95%:3.89-6.82) and eczema (OR = 2.35; 95%Cl:1.73-3.19) were independently associated to asthma. Environmental and socio-demographic factors were associated to asthma in adolescents in Rio de Janeiro, irrespective of the presence of others allergic diseases. Interventions acting on these factors may decrease the occurrence of asthma in this population. PMID- 17338788 TI - Trends in the prevalence and severity of asthma, rhinitis and atopic eczema in 6- to 7- and 13- to 14-yr-old children from the north-east of England. AB - The aims of the present study were to assess time trends in symptoms of asthma, rhinitis and atopic eczema among children in the north-east of England. Two cross sectional surveys 6 yr apart, 6- to 7- and 13- to 14 yr of age, using the International Study of Asthma and Allergies in Childhood, core questionnaire were performed. There was a general increase in symptoms for all the three conditions in both the age groups. In the age group 6- to 7 yr, the increase was generally the same in boys and girls, while in the age group 13- to 14 yr, the increase was generally more marked among boys. In the younger age group, indices related to lifetime diagnosed ever had asthma and having hay fever increased in girls but not in boys, while indices related to lifetime diagnosis of ever having eczema increased in boys and girls. In the older age group, indices related to lifetime diagnosis of ever had asthma slightly increased in boys but did not change in girls, while lifetime diagnosis of ever having hay fever slightly decreased in girls but did not change in boys. The prevalence of lifetime diagnosis of ever having eczema increased in boys and girls. Changes observed in the present study could be related to the changes in lifestyle or environmental factors, awareness or management of symptoms. PMID- 17338789 TI - Increase in the prevalence of rhinitis among Danish children from 1986 to 2001. AB - In recent decades, there has been a worldwide increase in the prevalence of atopic diseases. The aim of this study was to investigate whether there has been a change in the prevalence of rhinitis among children in Denmark from 1986 to 2001. We compared data from two random population-based samples of Danish children, aged 7-17 yr, who were examined in 1986 (n = 527) and 2001 (n = 480) using similar designs. Symptoms of rhinitis, skin test reactivity, and bronchial responsiveness to inhaled histamine were assessed. The prevalence of rhinitis increased from 11.8% in 1986 to 23.3% in 2001 (p < 0.001). The increase was most pronounced among subjects who suffered from non-allergic rhinitis (p < 0.001), and among subjects with severe symptoms (p < 0.001). The prevalence of asymptomatic positive skin prick test (SPT) decreased substantially (p < 0.001). A history of asthma and parental atopic disease were strong predictors of non allergic rhinitis, whereas a history of asthma, parental atopic disease, bronchial hyperresponsiveness, eczema, and age at examination were statistically significant predictors of allergic rhinitis. The prevalence of non-allergic rhinitis among Danish children has increased substantially from 1986 to 2001. Furthermore, in general more severe symptoms of rhinitis were observed in 2001 compared with 1986. These results underline the importance of using objective measurements such as skin test reactivity when estimating time trends in the prevalence of allergic airways disease, as clinical interviews alone can be misleading. PMID- 17338790 TI - Laser acupuncture and probiotics in school age children with asthma: a randomized, placebo-controlled pilot study of therapy guided by principles of Traditional Chinese Medicine. AB - Traditional Chinese Medicine (TCM) postulates an interaction between the lung as a Yin-organ and the large intestine as a Yang-organ. The aim of this pilot study was to investigate in asthmatic school age children whether treatment with laser acupuncture and probiotics according to TCM portends a clinical benefit to standard medical treatment performed according to pediatric guidelines. Seventeen children aged 6-12 yr with intermittent or mild persistent asthma were enrolled in this randomized, placebo-controlled, double-blind pilot study. Eight patients received laser acupuncture for 10 wk and probiotic treatment in the form of oral drops (living non-pathogenic Enterococcus faecalis) for 7 wk. Nine patients in the control group were treated with a laser pen which did not emit laser light and were given placebo drops. Peak flow variability (PFV) and forced expiratory volume in 1 s (FEV(1)) were measured and Quality of Life was assessed by a standardized questionnaire. Laser acupuncture and probiotics significantly decreased mean (standard deviation) weekly PFV as a measurement of bronchial hyperreactivity by -17.4% (14.2) in the TCM group vs. 2.2% (22.5) in the control group (p = 0.034). No significant effect was detected for FEV(1), Quality of Life criteria and additional medication. As an exploratory result, patients in the TCM group had fewer days of acute febrile infections when compared with the control group [1.14 (1.4) vs. 2.66 (2.5), p = 0.18]. In conclusion, this pilot study generates the hypothesis that the interactive treatment of lung and large intestine according to TCM by laser acupuncture and probiotics has a beneficial clinical effect on bronchial hyperreactivity in school age children with intermittent or mild persistent asthma and might be helpful in the prevention of acute respiratory exacerbations. These results should be confirmed by further studies. PMID- 17338791 TI - Increases in serum immunoglobulins to age-related normal levels in children with IgA and/or IgG subclass deficiency. AB - Immunoglobulins (Ig) A and G subclass deficiencies are common immune system disorders which cause morbidity especially between 2 and 6 yr of age. Prognosis of these defects and therapeutic approach is unclear. The aim of the present retrospective study was to review the clinical and laboratory records of 87 children with IgA and/or IgG subclass deficiency to determine whether these patients experience changes in serum Ig concentrations during follow-up and to give more clinic and laboratory information to the families about the course of these diseases. Among 87 patients studied, the most frequent defect was partial IgA deficiency combined with IgG3 subclass deficiency (41%). The other groups were as follows; partial IgA deficiency (32%), selective IgA deficiency (8%), partial IgA combined with IgG2-G4 subclass deficiency (6%), and IgG subclass deficiency (13%). The commonest clinical presentations were recurrent upper respiratory tract infections (76%), pneumonia (14%), acute gastroenteritis (3%), urinary tractus infection (3%), sinusitis (2%), and acute otitis media (2%). Atopy was widely represented in the patients studied (24%). The number of patients who were given prophylactic treatment with benzathine penicilline, prophylactic oral antibiotic, or oral bacterial extract to prevent infections was 68 (78%). Frequency of recurrent infections decreased from 7.9 +/- 4.9 per year to 2.5 +/- 2.3 in 68 patients receiving any prophylactic regimen; however, decrease in frequency of infections did not show any significant difference between different prophylactic groups. None of the patients in the selective IgA deficiency group had reached normal serum levels of IgA. At the age of 58.3 +/- 21.4 months, 52% of patients in partial IgA deficiency group and 51% of patients in partial IgA + IgG subclass deficiency group, serum IgA increased to normal ranges. Serum IgG subclass levels increased to normal range for age in 67% of patients in partial IgA + IgG subclass deficiency group and in 30% of patients in isolated IgG subclass deficiency group. The mean age for reaching age-related normal IgG subclass levels for these patients was 69.0 +/- 14.5 months. In conclusion, findings of this study suggest that IgA and/or IgG subclass deficiency may be either progressive or reversible disorders and emphasize the value of monitoring Ig levels in affected individuals. PMID- 17338792 TI - Kikuchi-Fujimoto disease of 16 children in a single center of Korea. AB - Kikuchi-Fujimoto disease (KFD) is subacute necrotizing lymphadenitis characterized by fever, leukopenia and cervical lymphadenopathy. There are few reports on the clinical characteristics and laboratory findings of KFD in the pediatric literature. In this study, we evaluate the characteristics and outcome of KFD in children. A total of 412 patients were studied with fever and peripheral lymphadenopathy at Pusan National University Hospital from January 1998 to December 2003. Among the total 412 there were 16 patients diagnosed with KFD by lymph node biopsy. We analyze the clinical, laboratory and outcome after review of the medical records retrospectively. The mean age of the patients was 10.6 +/- 3.4 yr (range: 4-17 yr). The male to female ratio was 1:1. Almost all patients, except two, had cervical lymph node swelling. The size of the involved lymph node was less than 4 cm in the greatest dimension in 75% of the patients. All the children had fever as the chief complaint and the mean duration of the fever was 17.7 +/- 11.2 days (range: 2-122 days). Approximately 87% of the patients had leukopenia (WBC < 4000/mm(3)) and 43.8% of the patients had a mild increase in the transaminases on liver function testing. A total of 8 out of the 16 patients were initially misdiagnosed as an infectious disease and treated with antibiotics which caused prolonged hospitalization for most patients. Six patients were treated with prednisone and the prolonged fever subsided immediately after steroid therapy. KFD should be considered in the differential diagnosis of prolonged fever in children with cervical lymphadenopathy. Early cervical lymph node biopsy is necessary to minimize inappropriate examinations and treatments in such cases. PMID- 17338793 TI - Dendritic cell-based immunotherapy of malignant melanoma: success and limitations. AB - Dendritic cells (DC) are professional antigen-presenting cells in the immune system which are able to induce primary T-cell responses. Because of their central role in the initiation of immune responses, DC are an important tool for tumor-antigen-specific immunotherapy of cancer. DC vaccination using tumor antigen-loaded DC has led to tumor regression in individual advanced-stage cancer patients. However, there is a discrepancy between strong and antigen-specific T cell responses in vaccinated cancer patients detectable ex vivo and only weak clinical responses. In most cases the immune system of advanced stage IV cancer patients allows only a temporary anti-tumor response and increasing evidence exists that active suppressive mechanisms of the immune system as well as of the tumor itself ultimately prevent "autoaggressive" immune reactions against the tumor. Active counter-regulation of effector T cells by tumor-antigen-specific regulatory T-cell (Treg) populations play a central role in limiting the efficacy of the vaccines. Nevertheless, recent studies have shown that DC,additionally activated byToll-Like-receptor ligands (TLRL) can neutralize these suppressive effects of Treg and facilitate the induction of long-lasting effector T cell responses even in the presence of activated Treg. These studies open a new way for "conditioning" of DC by TLRL and might significantly enhance the efficiency of DC-based melanoma vaccines in the future. PMID- 17338794 TI - Trichophyton mentagrophytes sive interdigitale? A dermatophyte in the course of time. AB - Originally, the Trichophyton (T.) mentagrophytes complex distinguished between the anthropophilic subspecies T. mentagrophytes var. interdigitale, T. mentagrophytes var. nodulare (synonym T. krajdenii), and T. mentagrophytes var. goetzii and the zoophilic subspecies T. mentagrophytes var. granulosum (rodents), T. mentagrophytes var. erinacei (hedgehog), and T. mentagrophytes var. quinckeanum (mice). In addition, two sexual species (teleomorph) of this complex are known. These are Arthroderma (A.) benhamiae Ajello and Cheng 1967 and Arthroderma vanbreuseghemii Takashio 1973. According to recent molecular studies,the species T.mentagrophytes is synonymous with only the zoophilic subspecies T.mentagrophytes var. quinckeanum which is rare in Western Europe. The anthropophilic subspecies of T. mentagrophytes, as well as many of the zoophilic strains, formerly differentiated as var. mentagrophytes or var. granulosum, are indistinguishable and are now designated T.interdigitale. The morphological differentiation between anthropophilic and zoophilic T. interdigitale strains by classical microscopical and biochemical methods is often problematic. In particular, it is impossible to differentiate between the zoophilic strains of T. interdigitale, T. mentagrophytes, and the Trichophyton anamorph of A. benhamiae. In these cases, molecular identification methods may be applied to answer epidemiological, taxonomical and therapeutic questions. PMID- 17338795 TI - Hydroxyethyl starch-induced itch: relevance of light microscopic analysis of semi thin sections and electron microscopy. AB - BACKGROUND: Hydroxyethyl starch (HES) is widely used as a plasma substitute for improving microcirculation. A major side effect of HES is severe pruritus caused by HES deposits in the skin. Since specific changes are difficult to see in paraffin sections, electron microscopy is the golden standard technique in the diagnosis of HES-induced skin disease. Our aim was to compare electron microscopic search for HES deposits with other techniques. PATIENTS AND METHODS: During the last ten years, we biopsied 21 patients suspected of having HES induced pruritus. We compared conventional microscopy with hematoxylin & eosin and toluidine blue-stained paraffin sections, toluidine blue-stained glycide ether-embedded, semithin sections and transmission electron microscopy. RESULTS: In 9 patients specific HES deposits could be found by evaluating toluidine blue stained semithin sections by light microscopy alone. In 6 of these cases electron microscopy was also done and confirmed the findings. In contrast, no specific findings due to HES deposits could be detected by conventional histology. CONCLUSIONS: If specific HES deposits are found in toluidine blue-stained, glycide ether-embedded semithin sections, electron microscopy is not required. PMID- 17338796 TI - Costs and quality of life in patients with moderate to severe plaque-type psoriasis in Germany: a multi-center study. AB - BACKGROUND: This study evaluated costs, disease severity and health-related quality of life (QoL) in patients with moderate to severe plaque-type psoriasis. PATIENTS AND METHODS: Patients with a 'psoriasis area and severity index' (PASI) > 12 and/or a body surface area (BSA) > 10 were enrolled in dermatological practices and hospital outpatient departments (n = 184) and the total costs of illness generated during the last 12 months were retrospectively calculated. QoL was assessed using the SF-36 and the DLQI. Participants were stratified into three subgroups according to the treatment received during the 1 year documentation period; a) patients without and b) patients with phototherapy or standard systemic therapy, and c) patients who had failed, were intolerant or had contraindications to at least two standard systemic therapies. The study was performed before biologics became available for the treatment of psoriasis in Germany. RESULTS: Included patients had severe skin symptoms (mean PASI 18.2) and a highly impaired QoL (mean DLQI 10.6). Total annual costs amounted to euro 6,709. Patients belonging to subgroup C had the most severe skin symptoms (mean PASI 22.2), the lowest QoL (mean DLQI 12.6), the highest hospitalization rate and largest loss of productivity. These patients produced the highest total costs of 8.831 euro/y. CONCLUSIONS: Patients who cannot (or can no longer) be adequately managed with standard treatments are characterized by high disease activity, high costs and reduced QoL. Improved treatment options particularly for these patients are medically necessary and appear economically sensible. PMID- 17338797 TI - Subacute cutaneous lupus erythematosus with bullae associated with porphyria cutanea tarda. AB - A 58-year-old patient presented with both annular and polycyclic as well as vesicular lesions. Histology revealed an interface dermatitis with focal hyperkeratosis and subepidermal blistering. Antinuclear antibodies were elevated (1 : 1280) and autoantibodies against Ro-SS-A were found. Based on these findings we made a diagnosis of subacute cutaneous lupus erythematosus (SCLE) with blister formation. Additionally, we diagnosed porphyria cutanea tarda (PCT) triggered by alcohol abuse. Treatment with systemic corticosteroids and low-dose hydroxy chloroquine led to rapid resolution of the skin changes. SCLE with blister formation is a rare cause of bullous skin eruptions and has to be distinguished from bullous autoimmune diseases as well as from bullous SLE. Recognition of concomitant PCT, which may be associated with all forms of LE, is especially important because of the therapeutic implications, since a reduced dosage of antimalarials is required. PMID- 17338798 TI - Congenital dermatofibrosarcoma protuberans: 30 years of follow-up. AB - Dermatofibrosarcoma protuberans (DFSP) is a rare fibrohistiocytic tumor that commonly appears in adult patients. Few cases of DFSP in childhood have been reported. We describe a case of congenital DFSP that had been incompletely excised in childhood, and again at 28 years of age. The 33-year-old woman presented with a recurrence. When comparing the histologic features of the previous specimens excised in 1970 and 30 years later, the similar typical storiform pattern of fibromatous cells was found. The small number of proliferation-marker-positive cells was not altered over the course of 30 years. In line with a few additional reports, we suggest that congenital dermatofibrosarcoma protuberans is a tumor with a low malignant potential. PMID- 17338799 TI - [Continuing medical education in Aesthetic Medicine: hands--on course on the usage of hyaluronic acids of different particle size on anatomic preparations]. AB - The Division of Evidence Based Medicine (dEBM), Clinic for Dermatology, Venerology and Allergology, Charite--Universitatsmedizin Berlin, offers on a regular basis workshops focusing on different areas of aesthetic medicine. Once a year a joint course is provided in cooperation with the Institute of Anatomy, offering the participants the possibility to improve their injection techniques as well as their knowledge on the facial anatomy. This course is focused on treatment with hyaluronic acids of different particle size. Besides the classical indications, it considers new indications such as correcting the shape of the nose or lacrimal groove. Thirteen physicians participated in the course, which was evaluated as very helpful as it improved not only the injection technique but also the knowledge of anatomy. PMID- 17338800 TI - Emergencies in allergy practice. PMID- 17338801 TI - [Nonpitting, livid induration of the skin]. PMID- 17338802 TI - [Single-step versus serial excision--intraoperative decision after stepwise preparation and situation sutures]. PMID- 17338803 TI - Coccygodynia. PMID- 17338805 TI - [The Department for Skin and Sexually Transmitted Diseases and in the frontier clinic of St. Polten]. PMID- 17338806 TI - [Targeted therapy of dermatofibrosarcoma with imatinib]. PMID- 17338807 TI - Detection of subtelomere imbalance using MLPA: validation, development of an analysis protocol, and application in a diagnostic centre. AB - BACKGROUND: Commercial MLPA kits (MRC-Holland) are available for detecting imbalance at the subtelomere regions of chromosomes; each kit consists of one probe for each subtelomere. METHODS: For validation of the kits, 208 patients were tested, of which 128 were known to be abnormal, corresponding to 8528 genomic regions overall. Validation samples included those with trisomy 13, 18 and 21, microscopically visible terminal deletions and duplications, sex chromosome abnormalities and submicroscopic abnormalities identified by multiprobe FISH. A robust and sensitive analysis system was developed to allow accurate interpretation of single probe results, which is essential as breakpoints may occur between MLPA probes. RESULTS: The validation results showed that MLPA is a highly efficient technique for medium-throughput screening for subtelomere imbalance, with 95% confidence intervals for positive and negative predictive accuracies of 0.951-0.996 and 0.9996-1 respectively. A diagnostic testing strategy was established for subtelomere MLPA and any subsequent follow up tests that may be required. The efficacy of this approach was demonstrated during 15 months of diagnostic testing when 455 patients were tested and 27 (5.9%) abnormal cases were detected. CONCLUSION: The development of a robust, medium-throughput analysis system for the interpretation of results from subtelomere assays will be of benefit to other Centres wishing to implement such an MLPA-based service. PMID- 17338808 TI - Are patients with non-ST elevation myocardial infarction undertreated? AB - BACKGROUND: The worse prognosis in patients without ST-elevation (non-STEMI) as compared to ST-elevation myocardial infarction (STEMI), may be due to treatment differences. We aimed to evaluate the differences in characteristics, treatment and outcome in patients with non-STEMI versus STEMI in an unselected patient population. METHODS: Individual patient data from all patients in our hospital with a discharge diagnosis of MI between Jan 2001 and Jan 2002 were evaluated. Follow-up data were obtained until December 2004. Patients were categorized according to the presenting electrocardiogram into non-STEMI or STEMI. RESULTS: A total of 824 patients were discharged with a diagnosis of MI, 29% with non-STEMI and 71% with STEMI. Patients with non-STEMI were significantly older and had a higher cardiovascular risk profile. They underwent less frequently coronary angiography and revascularization and received less often clopidogrel and ACE inhibitor on discharge. Long-term mortality was significantly higher in the non STEMI patients as compared to STEMI patients, 20% vs. 12%, p = 0.006, respectively. However, multivariate analysis showed that age, diabetes, hypertension and no reperfusion therapy (but not non-STEMI presentation) were independent and significant predictors of long-term mortality. CONCLUSION: In an unselected cohort of patients discharged with MI, there were significant differences in baseline characteristics, and (invasive) treatment between STEMI and non-STEMI. Long-term mortality was also different, but this was due to differences in baseline characteristics and treatment. More aggressive treatment may improve outcome in non-STEMI patients. PMID- 17338809 TI - A new molecular breast cancer subclass defined from a large scale real-time quantitative RT-PCR study. AB - BACKGROUND: Current histo-pathological prognostic factors are not very helpful in predicting the clinical outcome of breast cancer due to the disease's heterogeneity. Molecular profiling using a large panel of genes could help to classify breast tumours and to define signatures which are predictive of their clinical behaviour. METHODS: To this aim, quantitative RT-PCR amplification was used to study the RNA expression levels of 47 genes in 199 primary breast tumours and 6 normal breast tissues. Genes were selected on the basis of their potential implication in hormonal sensitivity of breast tumours. Normalized RT-PCR data were analysed in an unsupervised manner by pairwise hierarchical clustering, and the statistical relevance of the defined subclasses was assessed by Chi2 analysis. The robustness of the selected subgroups was evaluated by classifying an external and independent set of tumours using these Chi2-defined molecular signatures. RESULTS: Hierarchical clustering of gene expression data allowed us to define a series of tumour subgroups that were either reminiscent of previously reported classifications, or represented putative new subtypes. The Chi2 analysis of these subgroups allowed us to define specific molecular signatures for some of them whose reliability was further demonstrated by using the validation data set. A new breast cancer subclass, called subgroup 7, that we defined in that way, was particularly interesting as it gathered tumours with specific bioclinical features including a low rate of recurrence during a 5 year follow-up. CONCLUSION: The analysis of the expression of 47 genes in 199 primary breast tumours allowed classifying them into a series of molecular subgroups. The subgroup 7, which has been highlighted by our study, was remarkable as it gathered tumours with specific bioclinical features including a low rate of recurrence. Although this finding should be confirmed by using a larger tumour cohort, it suggests that gene expression profiling using a minimal set of genes may allow the discovery of new subclasses of breast cancer that are characterized by specific molecular signatures and exhibit specific bioclinical features. PMID- 17338810 TI - Factors influencing the utilization of research findings by health policy-makers in a developing country: the selection of Mali's essential medicines. AB - BACKGROUND: Research findings are increasingly being recognized as an important input in the formation of health policy. There is concern that research findings are not being utilized by health policy-makers to the extent that they could be. The factors influencing the utilization of various types of research by health policy-makers are beginning to emerge in the literature, however there is still little known about these factors in developing countries. The object of this study was to explore these factors by examining the policy-making process for a pharmaceutical policy common in developing countries; an essential medicines list. METHODS: A study of the selection and updating of Mali's national essential medicines list was undertaken using qualitative methods. In-depth semi-structured interviews and a natural group discussion were held with national policy-makers, most specifically members of the national commission that selects and updates the country's list. The resulting text was analyzed using a phenomenological approach. A document analysis was also performed. RESULTS: Several factors emerged from the textual data that appear to be influencing the utilization of health research findings for these policy-makers. These factors include: access to information, relevance of the research, use of research perceived as a time consuming process, trust in the research, authority of those who presented their view, competency in research methods, priority of research in the policy process, and accountability. CONCLUSION: Improving the transfer of research to policy will require effort on the part of researchers, policy-makers, and third parties. This will include: collaboration between researchers and policy-makers, increased production and dissemination of relevant and useful research, and continued and improved technical support from networks and multi-national organizations. Policy makers from developing countries will then be better equipped to make informed decisions concerning their health policy issues. PMID- 17338811 TI - Modulation of gene expression in a human cell line caused by poliovirus, vaccinia virus and interferon. AB - BACKGROUND: The project was initiated to describe the response of a human embryonic fibroblast cell line to the replication of two different viruses, and, more specifically, to look for candidate genes involved in viral defense. For this purpose, the cells were synchronously infected with poliovirus in the absence or presence of interferon-alpha, or with vaccinia virus, a virus that is not inhibited by interferon. By comparing the changes in transcriptosome due to these different challenges, it should be possible to suggest genes that might be involved in defense. RESULTS: The viral titers were sufficient to yield productive infection in a majority of the cells. The cells were harvested in triplicate at various time-points, and the transcriptosome compared with mock infected cells using oligo-based, global 35 k microarrays. While there was very limited similarities in the response to the different viruses, a large proportion of the genes up-regulated by interferon-alpha were also up-regulated by poliovirus. Interferon-alpha inhibited poliovirus replication, but there were no signs of any interferons being induced by poliovirus. The observations suggest that the cells do launch an antiviral response to poliovirus in the absence of interferon. Analyses of the data led to a list of candidate antiviral genes. Functional information was limited, or absent, for most of the candidate genes. CONCLUSION: The data are relevant for our understanding of how the cells respond to poliovirus and vaccinia virus infection. More annotations, and more microarray studies with related viruses, are required in order to narrow the list of putative defence-related genes. PMID- 17338812 TI - The influence of a verbal prompt on school lunch fruit consumption: a pilot study. AB - BACKGROUND: This study evaluated an environmental intervention intended to increase consumption of the fruit serving among elementary school children participating in the National School Lunch Program (NSLP). METHODS: Children's fruit consumption was measured in two schools by observation. In the intervention school, cafeteria workers provided the verbal prompt, "Would you like fruit or juice with your lunch?" as the children stood in line in front of the fruit serving options. The control school had the same fruit and 100% juice options available, but the cafeteria workers did not provide a verbal prompt to take a fruit serving. Two variables were assessed: (1) Did children leave the lunch line with a fruit serving on their trays? and (2) Did they subsequently eat the fruit serving? RESULTS: The average percentage of children who took a fruit serving was 60% in the control school and 90% in the intervention school. In both schools, approximately 80% of children ate the fruit on their tray. As a result, nearly 70% of the children in the intervention school consumed a fruit serving at lunch, while fewer than 40% did so in the control school. CONCLUSION: A simple verbal prompt appears to have a significant impact on the likelihood that children will take, and subsequently consume, a fruit serving as part of their purchased school lunch. If these findings are replicated, policymakers may consider adding verbal prompts to the serving policy of the NSLP in an effort to increase fruit consumption among school children. PMID- 17338814 TI - Response of lymphocyte subsets and cytokines to Shenyang prescription in Sprague Dawley rats with tongue squamous cell carcinomas induced by 4NQO. AB - BACKGROUND: The study was designed to investigate immunocompetence in relation to cancer progression in rat and to assess the effect of the traditional Chinese anti-cancer medicine, "Shenyang" prescription, on immunity. METHODS: 4 Nitroquinoline-1-oxide (4NQO) was administered to 80 Sprague-Dawley (SD) rats via the drinking water for up to 36 weeks. Tongue squamous cell carcinoma (SCC) was confirmed by pathological examination in 61 rats. "Shenyang" prescription was administered to subgroups of these rats, and blood samples were taken before and after treatment. Lymphocyte subsets were determined by flow cytometry. Serum Th1 and Th2-type cytokines were assessed by an enzyme-linked immunosorbent assay. RESULTS: As the cancer progressed at the tongue root, the percentage of CD3+CD4+ T lymphocytes and NK cells and the levels of IFN-gamma and IL-2 decreased gradually, while the percentage of CD3+CD8+ T lymphocytes and the levels of IL-4 and IL-10 increased. The CD4+/CD8+ ratios were lower in the cancer groups than in the control group. However, after administering "Shenyang" prescription, the levels of CD3+CD4+ T lymphocytes, NK cells, IFN-gamma and IL-2 increased, while the CD3+CD8+ T lymphocyte counts and the levels of IL-4 and IL-10 decreased. CONCLUSION: 4NQO-induced lesions were good models for exploring oral cavity carcinogenesis. The rats with 4NQO-induced SCC demonstrated abnormalities in lymphocyte subsets and a shift from Th1-type to Th2-type, which were good models for assessing the effect of anticancer agent on immunity. Oral cancer progression was associated with an aggressive disturbance of immune function. "Shenyang" prescription has the ability to improve the disturbance of immune function. PMID- 17338813 TI - Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases. AB - BACKGROUND: SPOUT methyltransferases (MTases) are a large class of S-adenosyl-L methionine-dependent enzymes that exhibit an unusual alpha/beta fold with a very deep topological knot. In 2001, when no crystal structures were available for any of these proteins, Anantharaman, Koonin, and Aravind identified homology between SpoU and TrmD MTases and defined the SPOUT superfamily. Since then, multiple crystal structures of knotted MTases have been solved and numerous new homologous sequences appeared in the databases. However, no comprehensive comparative analysis of these proteins has been carried out to classify them based on structural and evolutionary criteria and to guide functional predictions. RESULTS: We carried out extensive searches of databases of protein structures and sequences to collect all members of previously identified SPOUT MTases, and to identify previously unknown homologs. Based on sequence clustering, characterization of domain architecture, structure predictions and sequence/structure comparisons, we re-defined families within the SPOUT superfamily and predicted putative active sites and biochemical functions for the so far uncharacterized members. We have also delineated the common core of SPOUT MTases and inferred a multiple sequence alignment for the conserved knot region, from which we calculated the phylogenetic tree of the superfamily. We have also studied phylogenetic distribution of different families, and used this information to infer the evolutionary history of the SPOUT superfamily. CONCLUSION: We present the first phylogenetic tree of the SPOUT superfamily since it was defined, together with a new scheme for its classification, and discussion about conservation of sequence and structure in different families, and their functional implications. We identified four protein families as new members of the SPOUT superfamily. Three of these families are functionally uncharacterized (COG1772, COG1901, and COG4080), and one (COG1756 represented by Nep1p) has been already implicated in RNA metabolism, but its biochemical function has been unknown. Based on the inference of orthologous and paralogous relationships between all SPOUT families we propose that the Last Universal Common Ancestor (LUCA) of all extant organisms contained at least three SPOUT members, ancestors of contemporary RNA MTases that carry out m1G, m3U, and 2'O-ribose methylation, respectively. In this work we also speculate on the origin of the knot and propose possible 'unknotted' ancestors. The results of our analysis provide a comprehensive 'roadmap' for experimental characterization of SPOUT MTases and interpretation of functional studies in the light of sequence-structure relationships. PMID- 17338815 TI - Gene selection with multiple ordering criteria. AB - BACKGROUND: A microarray study may select different differentially expressed gene sets because of different selection criteria. For example, the fold-change and p value are two commonly known criteria to select differentially expressed genes under two experimental conditions. These two selection criteria often result in incompatible selected gene sets. Also, in a two-factor, say, treatment by time experiment, the investigator may be interested in one gene list that responds to both treatment and time effects. RESULTS: We propose three layer ranking algorithms, point-admissible, line-admissible (convex), and Pareto, to provide a preference gene list from multiple gene lists generated by different ranking criteria. Using the public colon data as an example, the layer ranking algorithms are applied to the three univariate ranking criteria, fold-change, p-value, and frequency of selections by the SVM-RFE classifier. A simulation experiment shows that for experiments with small or moderate sample sizes (less than 20 per group) and detecting a 4-fold change or less, the two-dimensional (p-value and fold change) convex layer ranking selects differentially expressed genes with generally lower FDR and higher power than the standard p-value ranking. Three applications are presented. The first application illustrates a use of the layer rankings to potentially improve predictive accuracy. The second application illustrates an application to a two-factor experiment involving two dose levels and two time points. The layer rankings are applied to selecting differentially expressed genes relating to the dose and time effects. In the third application, the layer rankings are applied to a benchmark data set consisting of three dilution concentrations to provide a ranking system from a long list of differentially expressed genes generated from the three dilution concentrations. CONCLUSION: The layer ranking algorithms are useful to help investigators in selecting the most promising genes from multiple gene lists generated by different filter, normalization, or analysis methods for various objectives. PMID- 17338816 TI - Microwave assisted synthesis of triazoloquinazolinones and benzimidazoquinazolinones. AB - BACKGROUND: Benzimidazoquinazolinones and related quinazolines are classes of heterocycles that are of considerable interest because of the diverse range of their biological properties. Although numerous classes of quinazolines have been conventionally synthesized, their syntheses have been suffered due to the multiple steps that sometimes have described in their preparation and also their chemical transformations that have been taken hours or even days to be completed. However, microwave energy can offer numerous benefits for performing synthesis of organic compounds including reduced pollution, increased reaction rates, yield enhancements, and cleaner chemistries. RESULTS: Synthesis of a series of triazoloquinazolinones and benzimidazoquinazolinones has been achieved under microwave irradiation. The products were obtained in nearly quantitative yields within few minutes during the reaction of aromatic aldehydes with 5-amino-1(H) 1,2,4-triazole (or 2-aminobenzimidazole) and dimedone in DMF. CONCLUSION: Microwave irradiation can be used as a facile and general method for the construction of a wide variety of triazoloquinazolinones and benzimidazoquinazolinones. The reaction involves a three component condensation (with potential for combinatorial work) being carried out with almost productive yields by microwave irradiation and considerably shortened reaction time. PMID- 17338817 TI - Microarray analysis of human leucocyte subsets: the advantages of positive selection and rapid purification. AB - BACKGROUND: For expression profiling to have a practical impact in the management of immune-related disease it is essential that it can be applied to peripheral blood cells. Early studies have used total peripheral blood mononuclear cells, and as a consequence the majority of the disease-related signatures identified have simply reflected differences in the relative abundance of individual cell types between patients and controls. To identify cell-specific changes in transcription it would be necessary to profile purified leucocyte subsets. RESULTS: We have used sequential rounds of positive selection to isolate CD4 and CD8 T cells, CD19 B cells, CD14 monocytes and CD16 neutrophils for microarray analysis from a single blood sample. We compared gene expression in cells isolated in parallel using either positive or negative selection and demonstrate that there are no significant consistent changes due to positive selection, and that the far inferior results obtained by negative selection are largely due to reduced purity. Finally, we demonstrate that storing cells prior to separation leads to profound changes in expression, predominantly in cells of the myeloid lineage. CONCLUSION: Leukocyte subsets should be prepared for microarray analysis by rapid positive selection. PMID- 17338818 TI - Solid serous microcystic adenoma of the pancreas. AB - BACKGROUND: Cystic neoplasms of the pancreas are less common than solid tumors, and portend a better prognosis. They can be divided into serous and mucinous subtypes, with the former behaving less aggressively and generally considered benign. Of the serous neoplasms, serous microcystic adenoma is the most common. An extremely rare solid variant of serous microcystic adenoma lacking secretory capability has been described. Herein, we present the fourth described case of this solid variant and review the literature. CASE PRESENTATION: We present a case of a 62 year-old man with a history of abdominal pain, who on CT scan was found to have a solid mass at the junction of the head and body of the pancreas. The patient was offered resection for diagnosis and treatment, and subsequently underwent distal pancreatectomy and splenectomy. Based on gross pathology, histology and immunohistochemistry, the mass was determined to be a solid serous microcystic adenoma. CONCLUSION: Solid serous microcystic adenoma shows similar histologic and immunohistologic features to its classic cystic counterpart, but lacks any secretory functionality. It appears to behave in a benign manner, and as such, surgical resection is curative for patients with this tumor. Furthermore, until more cases of solid SMA are identified to further elucidate its natural history and improve the reliability of preoperative diagnosis, surgical resection of this solid pancreatic tumor should be considered standard therapy in order to exclude malignancy. PMID- 17338819 TI - Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice. AB - BACKGROUND: Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal ganglion cells. Since ganglion cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect ganglion cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to ganglion cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured ganglion cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for ganglion cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the cell death phenotype. RESULTS: Inbred lines showed varying levels of susceptibility to optic nerve crush. DBA/2J mice were most resistant and BALB/cByJ mice were most susceptible. F1 mice from these lines inherited the DBA/2J phenotype, while N2 backcross mice exhibited the BALB/cByJ phenotype. F2 mice exhibited an intermediate phenotype. A Wright Formula calculation suggested as few as 2 dominant loci were linked to the resistance phenotype, which was corroborated by a Punnett Square analysis of the distribution of the mean phenotype in each cross. The levels of latent Bax mRNA were the same in both lines, and Bax alleles did not segregate with phenotype in N2 and F2 mice. CONCLUSION: Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving relatively few loci. Bax was excluded as a candidate gene for this phenotype. PMID- 17338820 TI - SpliceMiner: a high-throughput database implementation of the NCBI Evidence Viewer for microarray splice variant analysis. AB - BACKGROUND: There are many fewer genes in the human genome than there are expressed transcripts. Alternative splicing is the reason. Alternatively spliced transcripts are often specific to tissue type, developmental stage, environmental condition, or disease state. Accurate analysis of microarray expression data and design of new arrays for alternative splicing require assessment of probes at the sequence and exon levels. DESCRIPTION: SpliceMiner is a web interface for querying Evidence Viewer Database (EVDB). EVDB is a comprehensive, non-redundant compendium of splice variant data for human genes. We constructed EVDB as a queryable implementation of the NCBI Evidence Viewer (EV). EVDB is based on data obtained from NCBI Entrez Gene and EV. The automated EVDB build process uses only complete coding sequences, which may or may not include partial or complete 5' and 3' UTRs, and filters redundant splice variants. Unlike EV, which supports only one-at-a-time queries, SpliceMiner supports high-throughput batch queries and provides results in an easily parsable format. SpliceMiner maps probes to splice variants, effectively delineating the variants identified by a probe. CONCLUSION: EVDB can be queried by gene symbol, genomic coordinates, or probe sequence via a user-friendly web-based tool we call SpliceMiner (http://discover.nci.nih.gov/spliceminer). The EVDB/SpliceMiner combination provides an interface with human splice variant information and, going beyond the very valuable NCBI Evidence Viewer, supports fluent, high-throughput analysis. Integration of EVDB information into microarray analysis and design pipelines has the potential to improve the analysis and bioinformatic interpretation of gene expression data, for both batch and interactive processing. For example, whenever a gene expression value is recognized as important or appears anomalous in a microarray experiment, the interactive mode of SpliceMiner can be used quickly and easily to check for possible splice variant issues. PMID- 17338821 TI - A family practice breastfeeding education pilot program: an observational, descriptive study. AB - BACKGROUND: The United States Preventive Services Task Force found that effective interventions for extending breastfeeding duration are generally begun during the prenatal period, provide ongoing support for patients and combine information with face-to-face guidance. A 2001 literature review had similar findings but also found that employing a lactation consultant in the clinical setting may increase breastfeeding duration rates. Thus, a program was developed at a family practice office that employed a lactation consultant and followed the American Academy of Pediatrics' "Ten Steps to Support Parents' Choice to Breastfeed Their Baby." METHODS: The program distributed handouts at each prenatal and well-child visit (up to one year). Using questionnaires, a small audit project evaluated the program's impact on breastfeeding goals, duration, in-hospital exclusivity and maternal perception of success. Mothers completed goal surveys at baseline and post-intervention, usually while waiting for prenatal clinic visits. Duration was assessed by surveys completed during well-infant visits, postal mailings or telephone interviews at breastfeeding cessation, 6 months and 1 year. The outcomes measured were increases in goals, maternal perception of success, duration and in-hospital exclusivity. RESULTS: Participants included 33 women: 48% had a bachelor's or master's degree, 61% were non-Hispanic white, and 67% reported incomes of US$75,000 or higher. At baseline 5/31 planned to exclusively breastfeed for 4-6 months and 5/33 planned to breastfeed for 6-12 months. Post intervention there was a 200% increase (15/31) in the exclusively breastfeeding 4 6 month group and a 160% increase (13/33) in the 6-12 month duration group. Actual in-hospital exclusivity rates were 61%, 6-month duration rates were 73%, and 12-month rates were 33%. Over 75% of mothers reported feeling successful. CONCLUSION: This small pilot educational program may have significant impacts on breastfeeding goals. Setting and meeting goals may increase duration and in hospital exclusivity rates as well as enhance maternal self-perception and empowerment due to succeeding at their breastfeeding goals and/or experiencing a fulfilling breastfeeding relationship. PMID- 17338822 TI - Generalist care managers for the treatment of depressed medicaid patients in North Carolina: a pilot study. AB - BACKGROUND: In most states, mental illness costs are an increasing share of Medicaid expenditures. Specialized depression care managers (CM) have consistently demonstrated improvements in patient outcomes relative to usual primary care (UC), but are costly and may not be fully utilized in smaller practices. A generalist care manager (GCM) could manage multiple chronic conditions and be more accepted and cost-effective than the specialist depression CM. We designed a pilot program to demonstrate the feasibility of training/deploying GCMs into primary care settings. METHODS: We randomized depressed adult Medicaid patients in 2 primary care practices in Western North Carolina to a GCM intervention or to UC. GCMs, already providing services in diabetes and asthma in both study arms, were further trained to provide depression services including self-management, decision support, use of information systems, and care management. The following data were analyzed: baseline, 3- and 6-month Patient Health Questionnaire (PHQ9) scores; baseline and 6-month Short Form (SF) 12 scores; Medicaid claims data; questionnaire on patients' perceptions of treatment; GCM case notes; physician and office staff time study; and physician and office staff focus group discussions. RESULTS: Forty-five patients were enrolled, the majority with preexisting depression. Both groups improved; the GCM group did not demonstrate better clinical and functional outcomes than the UC group. Patients in the GCM group were more likely to have prescriptions of correct dosing by chart data. GCMs most often addressed comorbid conditions (36%), then social issues (27%) and appointment reminders (14%). GCMs recorded an average of 46 interactions per patient in the GCM arm. Focus group data demonstrated that physicians valued using GCMs. A time study documented that staff required no more time interacting with GCMs, whereas physicians spent an average of 4 minutes more per week. CONCLUSION: GCMs can be trained in care of depression and other chronic illnesses, are acceptable to practices and patients, and result in physicians prescribing guideline concordant care. GCMs appear to be a feasible intervention for community medical practices and to warrant a larger scale trial to test their appropriateness for Medicaid programs nationally. PMID- 17338823 TI - A cryptic promoter in potato virus X vector interrupted plasmid construction. AB - BACKGROUND: Potato virus X has been developed into an expression vector for plants. It is widely used to express foreign genes. In molecular manipulation, the foreign genes need to be sub-cloned into the vector. The constructed plasmid needs to be amplified. Usually, during amplification stage, the foreign genes are not expressed. However, if the foreign gene is expressed, the construction work could be interrupted. Two different viral genes were sub-cloned into the vector, but only one foreign gene was successfully sub-cloned. The other foreign gene, canine parvovirus type 2 (CPV-2) VP1 could not be sub-cloned into the vector and amplified without mutation (frame shift mutation). RESULTS: A cryptic promoter in the PVX vector was discovered with RT-PCR. The promoter activity was studied with Northern blots and Real-time RT-PCR. CONCLUSION: It is important to recognize the homologous promoter sequences in the vector when a virus is developed as an expression vector. During the plasmid amplification stage, an unexpected expression of the CPV-2 VP1 gene (not in the target plants, but in E. coli) can interrupt the downstream work. PMID- 17338824 TI - Acute adrenal crisis after orthopedic surgery for pathologic fracture. AB - BACKGROUND: Adrenal crisis after surgical procedure is a rare but potentially catastrophic life-threatening event. Its manifestations, such as hypotension, tachycardia, hypoxia, and fever mimic the other more common postoperative complications. Clinical outcome is dependent upon early recognition of the condition and proper management with exogenous steroid administration. CASE PRESENTATION: We report a 75-year-old man who presented with shock immediately after surgery for a femoral fracture from lung cancer metastasis. Anemia and severe hyponatremia were detected. Despite adequate fluid resuscitation, nonspecific symptoms including hypotension, tachycardia, hypoxia, fever and confusion occurred. Emergent CT revealed enlarged bilateral adrenal glands. Under the diagnosis of adrenal crisis due to metastatic infiltration of adrenal glands, the patient was treated with appropriate steroid replacement resulting in rapid improvement and recovery. CONCLUSION: We describe a case of adrenal crisis caused by the lack of adrenal reserve based on metastatic involvement and surgical stress, the first published case of adrenal crisis after surgery for a pathologic fracture from lung cancer metastasis. Surgeons treating pathologic fractures should be aware of this complication and familiar with its appropriate therapy because of increasing opportunity to care patients with metastatic bone tumors due to recent advances in cancer treatment. PMID- 17338825 TI - An efficient grid layout algorithm for biological networks utilizing various biological attributes. AB - BACKGROUND: Clearly visualized biopathways provide a great help in understanding biological systems. However, manual drawing of large-scale biopathways is time consuming. We proposed a grid layout algorithm that can handle gene-regulatory networks and signal transduction pathways by considering edge-edge crossing, node edge crossing, distance measure between nodes, and subcellular localization information from Gene Ontology. Consequently, the layout algorithm succeeded in drastically reducing these crossings in the apoptosis model. However, for larger scale networks, we encountered three problems: (i) the initial layout is often very far from any local optimum because nodes are initially placed at random, (ii) from a biological viewpoint, human layouts still exceed automatic layouts in understanding because except subcellular localization, it does not fully utilize biological information of pathways, and (iii) it employs a local search strategy in which the neighborhood is obtained by moving one node at each step, and automatic layouts suggest that simultaneous movements of multiple nodes are necessary for better layouts, while such extension may face worsening the time complexity. RESULTS: We propose a new grid layout algorithm. To address problem (i), we devised a new force-directed algorithm whose output is suitable as the initial layout. For (ii), we considered that an appropriate alignment of nodes having the same biological attribute is one of the most important factors of the comprehension, and we defined a new score function that gives an advantage to such configurations. For solving problem (iii), we developed a search strategy that considers swapping nodes as well as moving a node, while keeping the order of the time complexity. Though a naive implementation increases by one order, the time complexity, we solved this difficulty by devising a method that caches differences between scores of a layout and its possible updates. CONCLUSION: Layouts of the new grid layout algorithm are compared with that of the previous algorithm and human layout in an endothelial cell model, three times as large as the apoptosis model. The total cost of the result from the new grid layout algorithm is similar to that of the human layout. In addition, its convergence time is drastically reduced (40% reduction). PMID- 17338826 TI - Comparison of protein structures by growing neighborhood alignments. AB - BACKGROUND: Design of protein structure comparison algorithm is an important research issue, having far reaching implications. In this article, we describe a protein structure comparison scheme, which is capable of detecting correct alignments even in difficult cases, e.g. non-topological similarities. The proposed method computes protein structure alignments by comparing, small substructures, called neighborhoods. Two different types of neighborhoods, sequence and structure, are defined, and two algorithms arising out of the scheme are detailed. A new method for computing equivalences having non-topological similarities from pairwise similarity score is described. A novel and fast technique for comparing sequence neighborhoods is also developed. RESULTS: The experimental results show that the current programs show better performance on Fischer and Novotny's benchmark datasets, than state of the art programs, e.g. DALI, CE and SSM. Our programs were also found to calculate correct alignments for proteins with huge amount of indels and internal repeats. Finally, the sequence neighborhood based program was used in extensive fold and non topological similarity detection experiments. The accuracy of the fold detection experiments with the new measure of similarity was found to be similar or better than that of the standard algorithm CE. CONCLUSION: A new scheme, resulting in two algorithms, have been developed, implemented and tested. The programs developed are accessible at http://mllab.csa.iisc.ernet.in/mp2/runprog.html. PMID- 17338827 TI - Identification and characterization of bovine regulator of telomere length elongation helicase gene (RTEL): molecular cloning, expression distribution, splice variants and DNA methylation profile. AB - BACKGROUND: The genetic basis of telomere length heterogeneity among mammalian species is still not well understood. Recently, a gene named regulator of telomere length elongation helicase (RTEL) was identified and predicted to be an essential participant in species-specific telomere length regulation in two murine species. To obtain broader insights into its structure and biological functions and to ascertain whether RTEL is also a candidate gene in the regulation of telomere length diversity in other mammalian species, data from other mammals may be helpful. RESULTS: Here we report the cDNA cloning, genomic structure, chromosomal location, alternative splicing pattern, expression distribution and DNA methylation profile of the bovine homolog of RTEL. The longest transcript of bovine RTEL is 4440 nt, encompassing 24.8 kb of genomic sequence that was mapped to chromosome 13q2.2. It encodes a conserved helicase like protein containing seven characterized helicase motifs in the first 750 aa and a PIP box in the C-terminus. Four splice variants were identified within the transcripts in both the coding and 5'-untranslated regions; Western blot revealed that the most abundant splice variant SV-1 was translated to a truncated isoform of RTEL. The different 5'UTRs imply alternative transcription start sites in the promoter; Bovine RTEL was transcribed at the blastocyst stage, and expression levels were highest in adult testis, liver and ovary. DNA methylation analysis of tissues that differed significantly in expression level indicated that relatively low DNA methylation is associated with higher expression. CONCLUSION: In this study, we have identified and characterized a bovine RTEL homolog and obtained basic information about it, including gene structure, expression distribution, splice variants and profile of DNA methylation around two putative transcription start sites. These data may be helpful for further comparative and functional analysis of RTEL in mammals. PMID- 17338828 TI - Predicting mostly disordered proteins by using structure-unknown protein data. AB - BACKGROUND: Predicting intrinsically disordered proteins is important in structural biology because they are thought to carry out various cellular functions even though they have no stable three-dimensional structure. We know the structures of far more ordered proteins than disordered proteins. The structural distribution of proteins in nature can therefore be inferred to differ from that of proteins whose structures have been determined experimentally. We know many more protein sequences than we do protein structures, and many of the known sequences can be expected to be those of disordered proteins. Thus it would be efficient to use the information of structure-unknown proteins in order to avoid training data sparseness. We propose a novel method for predicting which proteins are mostly disordered by using spectral graph transducer and training with a huge amount of structure-unknown sequences as well as structure-known sequences. RESULTS: When the proposed method was evaluated on data that included 82 disordered proteins and 526 ordered proteins, its sensitivity was 0.723 and its specificity was 0.977. It resulted in a Matthews correlation coefficient 0.202 points higher than that obtained using FoldIndex, 0.221 points higher than that obtained using the method based on plotting hydrophobicity against the number of contacts and 0.07 points higher than that obtained using support vector machines (SVMs). To examine robustness against training data sparseness, we investigated the correlation between two results obtained when the method was trained on different datasets and tested on the same dataset. The correlation coefficient for the proposed method is 0.14 higher than that for the method using SVMs. When the proposed SGT-based method was compared with four per-residue predictors (VL3, GlobPlot, DISOPRED2 and IUPred (long)), its sensitivity was 0.834 for disordered proteins, which is 0.052-0.523 higher than that of the per residue predictors, and its specificity was 0.991 for ordered proteins, which is 0.036-0.153 higher than that of the per-residue predictors. The proposed method was also evaluated on data that included 417 partially disordered proteins. It predicted the frequency of disordered proteins to be 1.95% for the proteins with 5%-10% disordered sequences, 1.46% for the proteins with 10%-20% disordered sequences and 16.57% for proteins with 20%-40% disordered sequences. CONCLUSION: The proposed method, which utilizes the information of structure-unknown data, predicts disordered proteins more accurately than other methods and is less affected by training data sparseness. PMID- 17338829 TI - Primary resection versus neoadjuvant chemoradiation followed by resection for locally resectable or potentially resectable pancreatic carcinoma without distant metastasis. A multi-centre prospectively randomised phase II-study of the Interdisciplinary Working Group Gastrointestinal Tumours (AIO, ARO, and CAO). AB - BACKGROUND: The disappointing results of surgical therapy alone of ductal pancreatic cancer can only be improved using multimodal approaches. In contrast to adjuvant therapy, neoadjuvant chemoradiation is able to facilitate resectability with free margins and to lower lymphatic spread. Another advantage is better tolerability which consecutively allows applying multimodal treatment in a higher number of patients. Furthermore, the synopsis of the overall survival results of neoadjuvant trials suggests a higher rate compared to adjuvant trials. METHODS/DESIGN: As there are no prospectively randomised studies for neoadjuvant therapy, the Interdisciplinary Study Group of Gastrointestinal Tumours of the German Cancer Aid has started such a trial. The study investigates the effect of neoadjuvant chemoradiation in locally resectable or probably resectable cancer of the pancreatic head without distant metastasis on median overall survival time compared to primary surgery. Adjuvant chemotherapy is integrated into both arms. DISCUSSION: The protocol of the study is presented in condensed form after an introducing survey on adjuvant and neoadjuvant therapy in pancreatic cancer. PMID- 17338831 TI - Medical post-traumatic stress disorder: catching up with the cutting edge in stress research. AB - We briefly summarize two original research papers and a review article. We then review the formal structure of the diagnosis of post-traumatic stress disorder (PTSD) and discuss the use of continuous measures of PTSD in comparison with diagnostic instruments. Problems with distinguishing incident from prevalent PTSD cases lead to questions of whether medical PTSD is a new important problem. By examining current studies, we demonstrate that medical PTSD is lagging in fundamental and interventional research but we discuss how medical PTSD has unique opportunities to develop causal models that could inform the greater field of stress studies. We conclude by advocating that future medical PTSD research efforts should focus on understanding how fundamental brain processes are affected during acute medical stress. PMID- 17338830 TI - Key stages in mammary gland development. Secretory activation in the mammary gland: it's not just about milk protein synthesis! AB - The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critical energy providing elements of milk. Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation. While expression of milk protein genes increases during pregnancy and at secretory activation, the genes whose expression is more tightly regulated at this transition are those that regulate lipid biosynthesis. The sterol regulatory element binding protein (SREBP) family of transcription factors is recognized as regulating fatty acid and cholesterol biosynthesis. We propose that SREBP1 is a critical regulator of secretory activation with regard to lipid biosynthesis, in a manner that responds to diet, and that the serine/threonine protein kinase Akt influences this process, resulting in a highly efficient lipid synthetic organ that is able to support the nutritional needs of the newborn. PMID- 17338832 TI - Could pharmacogenetic data explain part of the interindividual sensitivity to methadone-induced respiratory depression? AB - In this issue of Critical Care, Megarbane and colleagues present a case report of methadone-induced respiratory depression and conduct a toxicokinetic/toxicodynamic evaluation. An opioid-dependent patient receiving methadone maintenance treatment (daily dose 70 mg) was found unconscious after ingesting 240 mg methadone and 2 mg flunitrazepam. Significant improvement in consciousness was achieved after an intravenous bolus of 0.3 mg naloxone followed by a continuous infusion of naloxone at 0.3 mg/hour. In patients receiving methadone maintenance treatment, an occasional intake of two to four times the usual daily dose of methadone is not an exceptional occurrence. However, few such patients experience episodes of life-threatening respiratory depression. Here, we discuss whether recent pharmacogenetic data could help us to understand interindividual variability in sensitivity to respiratory depression and, ultimately, to predict which patients are most likely to be affected. PMID- 17338833 TI - The long and difficult road to better evaluation of outcomes of prolonged mechanical ventilation: not yet a highway to heaven. AB - The study conducted by Cox and coworkers included in this issue of Critical Care demonstrates that prolonged mechanical ventilation (MV; defined as MV for 21 days or longer) is more specific than Diagnosis Related Group 541/542 as a marker of resource utilization, hospital costs and potentially ineffective care. These patients also had greater 1-year mortality and lower functional ability than patients who had received MV for 48 to 96 hours, despite having better baseline functional status. However, predictors of mortality and long-term functional outcomes that are reliable and accurate at the level of the individual patient remain to be identified. PMID- 17338835 TI - Do-not-resuscitate orders, unintended consequences, and the ripple effect. AB - Do-not-resuscitate (DNR) orders are commonly implemented in the critical care setting as a prelude to end-of-life care. This is often based on presumed prognosis for favorable outcome and interpretation of patient, family, and even physician wishes. While DNR orders explicitly apply only to an individual patient, the hospital culture and milieu in which DNR orders are implemented could potentially have an overall impact on aggressiveness of care across patients. As illustrated by the example of intracerebral hemorrhage, this may unexpectedly influence outcome even in patients without DNR orders in place. PMID- 17338836 TI - Trials stopped early for benefit? Not so fast! PMID- 17338837 TI - Infantile gastroenteritis in the community: a cost-of-illness study. AB - Rotavirus infections are the main cause of gastroenteritis in infants and children and it is expected that by the age of 5 years, nearly every child will have experienced at least one episode of rotavirus gastroenteritis. While severe cases are hospitalized, milder disease is either treated at home or by the GP, and as such the true prevalence of rotavirus infection in the community, and the burden of disease, is unknown. This paper reports the results of a cost-of illness study which was conducted alongside a structured community surveillance study. Forty-eight percent of our sample was found to have rotavirus acute gastroenteritis; and the average total cost of a child presenting with rotavirus gastroenteritis ranged between pound sterling 59 and pound sterling 143 per episode, depending on the perspective. Given the prevalence and severity of the disease, the estimated burden of rotavirus gastroenteritis to society is pound sterling 11.5 million per year. PMID- 17338838 TI - Aortic morphometry and microcephaly in hypoplastic left heart syndrome. AB - Microcephaly is a marker of abnormal fetal cerebral development, and a known risk factor for cognitive dysfunction. Patients with hypoplastic left heart syndrome have been found to have an increased incidence of abnormal neurodevelopmental outcomes. We hypothesized that reduced cerebral blood flow from the diminutive ascending aorta and transverse aortic arch in the setting of hypoplastic left heart syndrome may influence fetal growth of the brain. The purpose of our study, therefore, was to define the prevalence of microcephaly in full-term infants with hypoplastic left heart syndrome, and to investigate potential cardiac risk factors for microcephaly. We carried out a retrospective review of full-term neonates with hypoplastic left heart syndrome. Eligible patients had documented indexes of birth weight, and measurements of length, and head circumference, as well as adequate echocardiographic images for measurement of the diameters of the ascending aorta and transverse aortic arch. We used logistic regression for analysis of the data. A total of 129 neonates met the criteria for inclusion, with 15 (12%) proving to have microcephaly. The sizes of their heads were disproportionately smaller than their weights (p less than 0.001) and lengths (p less than 0.001) at birth. Microcephaly was associated with lower birth weight (p less than 0.001), lower birth length (p equal to 0.007), and a smaller diameter of the ascending aorta (p equal to 0.034), but not a smaller transverse aortic arch (p equal to 0.619), or aortic atresia (p equal to 0.969). We conclude that microcephaly was common in this cohort of neonates with hypoplastic left heart syndrome, with the size of the head being disproportionately smaller than weight and length at birth. Microcephaly was associated with a small ascending aorta, but not a small transverse aortic arch. Impairment of somatic growth may be an additional factor in the development of microcephaly in these neonates. PMID- 17338839 TI - AMI after epinephrine. PMID- 17338840 TI - AMI after epinephrine. PMID- 17338841 TI - Clarification--"pretreatment" in RSI. PMID- 17338842 TI - Emergency department use by CTAS Levels IV and V patients. AB - INTRODUCTION: Many emergency department (ED) visits are non-urgent. Postulated reasons for these visits include lack of access to family physicians, convenience and 24/7 access, perceived need for investigations or treatment not available elsewhere, and as a mechanism for expedited referral to other specialists. We conducted a patient survey to determine why non-urgent patients use our tertiary care ED. Our primary objective was to determine how often the lack of a family physician was associated with non-urgent ED use. METHODS: The survey was administered to Canadian Emergency Department Triage and Acuity Scale (CTAS) Level IV and V patients who attended the ED of the Queen Elizabeth II Health Sciences Centre in Halifax, NS, from March 7 to March 13, 2005. RESULTS: Of the 352 eligible patients, 235 completed the survey (response rate, 67%). Fifty-six percent (132/235) had an acute medical problem of less than 48 hours, including 48% (114/235) with a recent injury. Thirty-four percent (82/235) had been referred to the ED, 49% (114/235) believed they required a specific service that was unavailable elsewhere (e.g., radiology, suturing, casting) and 43% (100/235) presented because of self-perceived urgency of their condition. Eighty-four percent (198/235) had a family physician; 23% (55/235) used the ED because of limited access to their family physician and 3% (6/235) used the ED because they did not have a family physician. CONCLUSIONS: In this setting, most non-urgent ED visits involved patients who required a specific service offered by the ED, patients who believed their condition was urgent, or patients who were referred from the community to the ED. From a patient perspective, relatively few visits would be considered inappropriate. Lack of a family physician was not associated with non-urgent ED use; however, inability to obtain timely access to the FP was a factor in one-quarter of cases. PMID- 17338843 TI - Effect of the SARS outbreak on visits to a community hospital emergency department. AB - OBJECTIVES: To examine the effect of severe acute respiratory syndrome (SARS) on visits to a community hospital emergency department (ED) during the early stage of the Toronto outbreak in 2003 and for the same period in 2004. We focused on visits for respiratory illness (SARS-like symptoms) and different age groups. METHODS: This study is a retrospective review of ED discharge diagnoses obtained from a computerized database, examining the 4-week period starting March 28 for the years 2001-2004. We obtained the discharge diagnosis, age and visit date for each ED patient during the relevant time intervals, then compared visit data from 2003 and 2004 with a baseline derived from the average number of visits during 2001 and 2002. We constructed groupings based on age and respiratory-illness symptoms. RESULTS: During the SARS outbreak in 2003, ED visits declined by 21% (95% confidence interval [CI], 18%-24%) over the 4-week study period. The greatest reduction was for combined infant and toddler visits (69%; 95% CI, 58% 79%); these did not recover the following year. However, during the SARS outbreak there was a large increase in the number of visits for respiratory illnesses in adults (61%; 95% CI, 46%-75%) and in teenagers (132%; 95% CI, 82%-182%). CONCLUSIONS: During the SARS outbreak, total ED visits fell. The relative decline was most notable for infants and toddlers. By contrast, there was an increase in respiratory illness-related visits for adults and teenagers. In 2004, the year following the SARS outbreak, visit patterns shifted toward baseline levels, but ED visits by infants and toddlers remained depressed. PMID- 17338844 TI - Systematic review of randomized controlled trials of therapeutic hypothermia as a neuroprotectant in post cardiac arrest patients. AB - OBJECTIVE: Several randomized controlled trials have suggested that mild induced hypothermia may improve neurologic outcome in comatose cardiac arrest survivors. This systematic review of randomized controlled trials was designed to determine if mild induced hypothermia improves neurologic outcome, decreases mortality, or is associated with an increased incidence of adverse events. DATA SOURCES: The following databases were reviewed: Cochrane Controlled Trials Register (Issue 4, 2005), MEDLINE (January 1966 to November 2005), EMBASE (1980 to November 2005), CINAHL (1982 to November 2005) and Web of Science (1989 to November 2005). For each included study, references were reviewed and the primary author contacted to identify any additional studies. STUDY SELECTION: Studies that met inclusion criteria were randomized controlled trials of adult patients (>18 years of age) with primary cardiac arrest who remained comatose after return of spontaneous circulation. Patients had to be randomized to mild induced hypothermia (32 degrees C-34 degrees C) or normothermia within 24 hours of presentation. Only studies reporting pre-determined outcomes including discharge neurologic outcome, mortality or significant treatment-related adverse events were included. There were no language or publication restrictions. DATA SYNTHESIS: Four studies involving 436 patients, with 232 cooled to a core temperature of 32 degrees C-34 degrees C met inclusion criteria. Pooled data demonstrated that mild hypothermia decreased in-hospital mortality (relative ratio [RR] 0.75; 95% confidence interval [CI], 0.62-0.92) and reduced the incidence of poor neurologic outcome (RR 0.74; 95% CI, 0.62-0.84). Numbers needed to treat were 7 patients to save 1 life, and 5 patients to improve neurologic outcome. There was no evidence of treatment-limiting side effects. CONCLUSIONS: Therapeutically induced mild hypothermia decreases in-hospital mortality and improves neurologic outcome in comatose cardiac arrest survivors. The possibility of treatment-limiting side effects cannot be excluded. PMID- 17338845 TI - Hyperglycemia in acutely ill emergency patients--cause or effect? AB - OBJECTIVES: To clarify the benefits, risks and timing of glucose control and intensive insulin therapy in several groups, specifically the neurologic, cardiac and septic populations of patients, commonly seen in the emergency department. METHODS: Electronic search of MEDLINE (1966-2005; once with PubMed and once with Ovid) and Embase (1980-2005) using the terms insulin and glucose combined with emergency medicine, intensive care, cardiology and emergency department. RESULTS: There is considerable controversy in the literature surrounding the use of strict glucose control in cardiac, neurologic and septic patients. Much of this literature is non-randomized, and the timing of therapy is poorly investigated. CONCLUSIONS: Hyperglycemia is associated with adverse outcomes in acutely ill neurologic, cardiac and septic patients, but it remains unclear whether this is a causative association. Glucose control and intensive insulin therapy may be useful in some patient subgroups; however, controlled trials of aggressive glycemic control have provided insufficient evidence to justify subjecting patients to the real risks of iatrogenic hypoglycemia. We recommend a cautious approach to the control of glucose levels in acutely ill emergency department patients, with a target glucose of below 8 to 9 mmol/L. PMID- 17338846 TI - Acute ischemic upper limb in a young man: an emergency presentation. PMID- 17338848 TI - You need tube, me give one amp of etomidate and SUX. PMID- 17338847 TI - Etomidate for rapid sequence intubation in the emergency department: is adrenal suppression a concern? AB - Etomidate has become one of the most commonly used induction agents in the United States during emergency department (ED) endotracheal intubation. While etomidate may be popular, concerns have been raised about possible adrenal suppression and subsequent adverse effects. In this paper we critically evaluate the recent literature and perspectives regarding the effect of etomidate on the adrenocortical system. PMID- 17338849 TI - Posterior sternoclavicular joint dislocation: case report and discussion. AB - The sternoclavicular joint is the most frequently mobilized non-axial, major joint, but is the least frequently dislocated. Most sternoclavicular dislocations are anterior. When posterior sternoclavicular joint dislocations do occur, they may present with a variety of signs and symptoms, including serious intrathoracic injuries. We discuss the case of a patient with a subacute posterior sternoclavicular dislocation who presented to the emergency department 2 months after being hit in the posterior neck. We also review the signs, symptoms and management of posterior sternoclavicular dislocation and the literature on this topic. PMID- 17338850 TI - Bowel perforation after single-dose activated charcoal. AB - Patients presenting to the emergency department (ED) after medication overdose are often given activated charcoal initially for gastrointestinal decontamination. Complications of charcoal are rare, but do occur. The following case describes a patient with pre-existing undiagnosed diverticular disease who developed sigmoid perforation after a single dose of activated charcoal, given without cathartic for a drug overdose. A literature search revealed no other cases of bowel perforation associated with single-dose activated charcoal. This case report discusses adverse effects associated with activated charcoal and the role of cathartics in gastrointestinal decontamination. PMID- 17338851 TI - Lamotrigine as a possible cause of QRS prolongation in a patient with known seizure disorder. AB - Lamotrigine and felbamate are 2 newer anticonvulsant medications used to control refractory partial and generalized seizures. Although several cases of lamotrigine toxicity secondary to acute intentional or unintentional overdose have been described, there is little published information related to potential side-effects associated with the therapeutic use of these agents. Described is a case of a 22-year-old woman who presented to the emergency department after experiencing 2 seizure-like episodes. Findings on evaluation included nystagmus, ataxia, widening of the QRS complex and right-axis deviation on ECG. The patient reported only therapeutic use of her medications. The lamotrigine level was 14.8 mg/L. The mechanism of action for lamotrigine is blockade of the sodium channels; therefore, the patient was treated with intravenous sodium bicarbonate with resultant QRS narrowing following administration. PMID- 17338852 TI - Primary amebic meningoencephalitis: a silent killer. AB - One week after swimming in a man-made lake, a 9-year-old boy presented to the emergency department with headache, vomiting and lethargy. He had neck pain upon flexion and was unable to stand or walk. Cerebrospinal fluid examination revealed trophozoite and diflagellate forms consistent with Naegleria fowleri, an ameba species known to cause primary amebic meningoencephalitis. Despite aggressive management with amphotericin B and rifampin, he died 2 days later. This case report describes the clinical presentation, diagnostic findings and management of this uncommon but lethal entity. PMID- 17338854 TI - APOBEC3G and HIV-1: strike and counterstrike. AB - APOBEC3G (A3G), a deoxycytidine deaminase, is a powerful host antiretroviral factor that can restrict HIV-1 infection. This restriction is counteracted by the HIV-1 virion infectivity factor (Vif) protein, whose activity culminates in depletion of A3G from infected cells. In the absence of Vif, viruses encapsidate A3G, which acts in part to mutate viral DNA formed during reverse transcription upon subsequent infection of a new cell. Cellular A3G also functions as a post entry restriction factor for HIV in resting CD4 T cells, where it resides in a low molecular mass form. Unfortunately, this barrier is forfeited when CD4 T cells are activated because A3G is recruited into inactive high molecular mass ribonucleoprotein complexes. In addition to restricting HIV, A3G and related deaminases may counter other retroviruses and protect the cell from endogenous mobile retroelements. Understanding A3G complex assembly and its interplay with HIV Vif may make possible future development of a new class of HIV therapeutic agents. PMID- 17338855 TI - Pathogenesis of HIV in the gastrointestinal tract. AB - Gut-associated lymphoid tissue (GALT) is an important site for early HIV replication and severe CD4+ T-cell depletion. Initiation of highly active antiretroviral therapy leads to incomplete suppression of viral replication and substantially delayed and only partial restoration of CD4+ T cells in GALT compared with peripheral blood. Persistent viral replication in GALT leads to replenishment and maintenance of viral reservoirs. Increased levels of inflammation, immune activation, and decreased levels of mucosal repair and regeneration contribute to enteropathy. Assessment of gut mucosal immune system will provide better insights into the efficacy of highly active antiretroviral therapy in immune restoration and suppression of viral reservoirs. PMID- 17338856 TI - Disorders of immune reconstitution in patients with HIV infection responding to antiretroviral therapy. AB - Patients with HIV infection who were very immunodeficient before achieving a virologic response to antiretroviral therapy (ART) may experience various disorders of immune reconstitution. Immune restoration disease occurs in approximately 10% to 50% of patients and results from the restoration of a pathogen-specific immune response that causes immunopathology and presents as tissue inflammation or cellular proliferative disease. Opportunistic infections occur in no more than 5% of patients, but approximately one half of these patients have higher than expected CD4 T-cell counts and appear to have residual immune dysfunction. Autoimmune disease may arise because the reconstituted immune system confers an increased susceptibility to immune dysregulation but there may be different mechanisms because Graves' disease presents after a median time of about 2 years of ART whereas systemic lupus erythematosus presents earlier. Persistent CD4 T-cell deficiency (< 500/microL) affects up to 60% of patients and appears to reflect depletion of the naive T-cell pool that results from low production and/or increased turnover of cells. PMID- 17338857 TI - Bacterial vaginosis and host immunity. AB - Bacterial vaginosis (BV) has been associated with severe medical consequences including induction of preterm birth and increasing susceptibility to infection by HIV and other genital tract pathogens. Although the mechanism by which BV induces these changes is not yet fully defined, the presence of BV is accompanied by immunologic changes in the lower genital tract environment. The most striking change is the induction of higher levels of proinflammatory cytokines, although this is not accompanied by increased levels of neutrophils. Increased cytokine levels are likely induced by bacterial products present in BV through innate immune recognition pathways such as the toll-like receptors. Recent studies show that changes in HIV susceptibility and HIV detection are associated with changes in bacterial flora. Further research is needed to identify the relative contributions of immune pathways and bacterial flora toward the pathogenic alterations that occur in BV. PMID- 17338858 TI - Current concepts of HIV transmission. AB - The epithelial surface acts as an effective barrier against HIV. The various mucosal surfaces possess specific mechanisms that help prevent the transmission of virus. Yet, HIV manages to cross these barriers to establish infection, and this is enhanced in the presence of physical trauma or pre-existing sexually transmitted infections. Once breached, the virus accesses numerous cells such as dendritic cells, T cells, and macrophages present in the underlying epithelia. Although these cells should contribute to innate and adaptive immunity to infection, they also serve as permissive targets to HIV and help in the initiation and dissemination of infection. Understanding how the various mucosal surfaces, and the cells within them, respond to the presence of HIV is essential in the design of therapeutic agents that will help to prevent HIV transmission. PMID- 17338859 TI - The impact of viral and host elements on HIV fitness and disease progression. AB - Twenty-five years after the emergence of HIV onto the global scene, multiple advancements have been made in the understanding of HIV pathology. Thanks to the development of antiretroviral therapies, growing numbers of individuals with HIV infection experience slowed or halted acceleration to AIDS. Despite this, new HIV infections and AIDS-related morbidity and mortality are still common in the highly active antiretroviral therapy era. Recently, we and others have identified viral replicative fitness as a major determinant of HIV disease progression, which could have a major impact in the clinical setting. Therefore, in this review, we will discuss host and viral factors that affect viral fitness and its relationship on HIV pathogenesis. PMID- 17338861 TI - [Mean length of stay and prognosis in unstable angina. Results from the ARIAM database]. AB - BACKGROUND AND OBJECTIVE: The objective of this project is to investigate the factors predicting mortality and mean length of stay in patients diagnosed with unstable angina (UA) during admission to the Intensive Care Unit or Critical Care Unit (ICU/CCU). PATIENTS AND METHOD: A retrospective cohort study including all the UA patients listed in the Spanish ARIAM register. The study period comprised from June, 1996 to December, 2003. The follow-up period is limited to the stay in the ICU/CCU. One univariate analysis was performed between deceased and live patients; and another between prolonged and non-prolonged stay patients. Three multivariate analyses were also performed; one to evaluate the factors related to mortality, another to evaluate the variables associated to percutaneous coronary intervention (PCI) and another to evaluate the factors associated to the prolonged mean stay in ICU/CCU. RESULTS: 14,096 patients with UA were included in the study. The UA mortality rate during ICU/CCU admission was 1.1%. Mortality was associated to Killip classification, age, the need for CPR, development of cardiogenic shock, development of arrhythmia (such as VF, sinus tachycardia or high-degree atrioventricular block) and diabetes; whereas patients who smoke were associated to a lower mortality rate. PCI was only performed in 1,226 patients (8.9%), increasing over the years. The PCI-predicting variables were: age, being referred from another hospital, smoking, presenting prior acute myocardial infarction (AMI), complications consisting of cardiogenic shock or high-degree atrioventricular block and being treated with oral beta blockers. The mean length of stay in ICU/CCU was 3.15 (18.65) days (median, 2 days), depending on age, a coronariography having previously been performed, the Killip classification, having required coronariography and PCI or echocardiography or mechanical ventilation, and presenting complications such as angina that is difficult to control, arrhythmia, right ventricular failure or death. CONCLUSIONS: The factors are associated to mortality were; greater age, diabetes, Killip classification, arrhythmia, cardiogenic shock and the need for CPR, whereas smoking is associated to a lower mortality rate. The patients on whom PCI was performed represent a less severe population. Management has changed over the years, with an increase in PCI. A prolonged mean length of stay is associated to the appearance of arrhythmia, right or left heart failure, angina that is difficult to control, age and PCI. PMID- 17338860 TI - Role of immune activation in HIV pathogenesis. AB - T-cell activation has long been considered a central mediator of HIV pathogenesis. High T-cell activation levels predict more rapid disease progression in untreated patients and decreased treatment-mediated CD4+ T-cell gains during antiretroviral therapy, independent of plasma HIV RNA levels, and may be the primary feature distinguishing pathogenic from nonpathogenic primate models of HIV infection. Studies in animal models and individuals with HIV infection continue to enhance our understanding of how T-cell activation causes immunodeficiency during HIV infection. The goal of these studies is to identify specific mechanisms that can be targeted by novel immune-based therapies for patients who have thus far been unable to recover normal immune function despite years of antiretroviral therapy. Although most immune-based therapies targeting T cell activation have been unsuccessful to date, recent scientific developments have focused attention on specific pathways that may be exploited by future generations of immune-based therapies. PMID- 17338862 TI - [Systematic review: are major opioids effective in the treatment of musculoskeletal pain?]. AB - BACKGROUND AND OBJECTIVE: To evaluate the efficacy of major opioids in the treatment of musculoskeletal pain. MATERIAL AND METHOD: Systematic review. A sensitive search strategy was undertaken in MEDLINE and EMBASE up to April 2005. The Cochrane Library and the abstracts of the 2004-2005 meetings of the American College of Rheumatology were also hand searched. All randomized controlled trials of major opiods in patients with musculoskeletal pain were selected. An analytical review was performed and evidence tables produced. A meta-analysis was run when appropriate. RESULTS: We obtained 427 references from the search, (27 duplicated from MEDLINE and EMBASE, 2 from the Cochrane Library, and 5 abstracts), of which 68 articles plus one meeting abstract were selected for detailed analysis. Of these, 23 finally met the inclusion criteria. Combined analysis of oral major opioids versus placebo showed significant improvement in pain relief in patients with osteoarthritis. CONCLUSIONS: Specific major opioids can reduce pain in patients with chronic musculoskeletal disorders. The clinical trials report positive effects on pain and the meta-analysis confirms these effects. PMID- 17338864 TI - [Biomedical research and society: ambivalences and contradictions]. PMID- 17338863 TI - [Immigration and HIV-1 infection: clinical manifestations, subtypes and evolution of 78 patients attended during the last 5 years]. AB - BACKGROUND AND OBJECTIVE: To analyse the characteristics and HIV-1 subtype in a group of HIV+ hospitalised immigrants in our Infectious Diseases Unit. PATIENTS AND METHOD: Clinical reports of 78 immigrants HIV+ were reviewed. HIV-1 subtyping was carried out examining the protease and transcriptase genes by phylogenetic analysis. Statistical study was done by SPSS 11.0 program. RESULTS: 57% of patients come from sub-Saharian Africa. Mainly they had been infected by heterosexual contact. HIV was diagnosed at the hospitalisation time in 35 cases. Only 28% were receiving highly active antiretroviral therapy and 48,7% had CD4+ cells less than 200/microl. The more frequent diagnosed diseases were: tuberculosis (20.5%), candidiasis (24.4%), bacterial pneumonia (19.2%) and malaria (21.8%). HIV-1 subtype B was isolated in 26 patients, none Africans. Twenty nine individuals (52.8%) were infected with HIV-1 non-B subtypes. Relationship between HIV-1 subtype, immunodepression, diagnosed diseases and origin countries was not found apart from malaria. CONCLUSIONS: Most HIV-1 infected immigrants are from Africa, being predominantly infected with HIV-1 non B subtypes. No relationship between HIV subtype and diagnosed diseases was found. PMID- 17338865 TI - [Medical-legal analysis of aggresssion towards health professionals. An approach to a silent reality and its consequences on health]. PMID- 17338866 TI - [Antiretroviral therapy and mitochondrial toxicity]. AB - The introduction of highly active antiretroviral therapy for the treatment of human immunodeficiency virus (HIV) infection has led to substantial reduction in morbidity and near-complete suppression of HIV-1 replication. This progress has been tempered by a growing number of new adverse effects. Mitochondrial toxicity is one aspect of these long-term toxicities of antiretroviral drugs, with the role of nucleoside analogs being particularly underlined. Some cases of impaired mitochondrial function have been clearly identified, such as pancreatitis, neuropathy, miopathy and lactic acidosis. Beyond the inhibition of DNA polymerase g using nucleoside analogs, it appears that several physiopathologic mechanisms interact to explain the observed toxicity. At present there is no reliable method to detect subclinical mitochondrial toxicity. There is no proven effective therapy for antiretroviral therapy-associated mitochondrial toxicity other than ceasing the implicated agent, and even with this strategy, resolution of symptoms may be incomplete. Therefore, investigation of mitochondrial toxicity of new compounds or new combinations is of growing interest for the clinical application of antiretroviral agents. PMID- 17338867 TI - [Estimation of the presence of cardiovascular events and direct costs associated with chronic obstructive pulmonary disease in an ambulatory setting]. PMID- 17338868 TI - [Family and gender violence from the point of view of health professionals]. PMID- 17338869 TI - [Contact dermatitis after black henna tattoo]. PMID- 17338870 TI - [Occipital condyle syndrome as initial manifestation of a pulmonary neoplasm]. PMID- 17338871 TI - [Fat embolism]. PMID- 17338872 TI - [What exactly is atrial fibrillation and how do we diagnose it?]. PMID- 17338873 TI - [Cardiac resynchronization therapy: when the pacing site really matters]. PMID- 17338874 TI - [Notes on the bibliometric context of Revista Espanola de Cardiologia]. PMID- 17338875 TI - [Differentiating between atrial flutter and atrial fibrillation using right atrial bipolar endocardial signals]. AB - INTRODUCTION AND OBJECTIVES: Contemporary atrial pacemakers incorporate pacing modes for treating atrial arrhythmias. Because atrial fibrillation in the right atrium can exhibit an organized pattern, it can be difficult to differentiate from atrial flutter. We assessed criteria for discriminating between atrial flutter and organized atrial fibrillation when using a bipolar electrode in the right atrium. METHODS: Simultaneous bipolar electrograms of the right and left atria were obtained in 45 patients: Group I comprised 15 patients with atypical flutter, Group II comprised 15 with typical flutter, and Group III, 15 with organized atrial fibrillation in the right atrium. The mean cycle length and the mean variation in cycle length observed over 15 seconds in electrograms of the right atrium were recorded. RESULTS: The mean cycle length was longer in Groups I and II than in Group III (232 [21] ms and 234 [24] ms, respectively, versus 183 [16] ms; P< .001). The mean variation in cycle length was less in Groups I and II than in Group III (16 [7] ms and 13 [4] ms, respectively, versus 22 [7] ms; P< .01). A cycle length > or =203 ms discriminated atrial flutter from atrial fibrillation with a sensitivity of 97% and a specificity of 87%. A cycle length variation < or =18 ms discriminated atrial flutter from atrial fibrillation with a sensitivity of 70% and a specificity of 80%. CONCLUSIONS: Cycle length was better than the variation in cycle length for differentiating atrial flutter from organized atrial fibrillation. PMID- 17338876 TI - [Double-wire technique for implanting a left ventricular venous lead in patients with complicated coronary venous anatomy]. AB - INTRODUCTION AND OBJECTIVES: Occasionally, implanting a left ventricular pacing electrode for cardiac resynchronization therapy via the coronary sinus may be complicated by the presence of anatomical structures that obstruct the access to the target vein. Our objective was to report on experience using a double-wire technique for implanting left ventricular venous leads gained at the Dr Negrin Hospital in Gran Canaria, Spain. METHODS: In 20 (12%) of 170 consecutive patients (67 [9] years, 72% male) undergoing implantation of a cardiac resynchronization device, a second parallel hydrophilic guidewire had to be used during lead implantation in the target vein as implantation was impossible without using this technique. RESULTS: Implantation using a conventional approach was impossible because there was severe tortuosity at the vessel entrance in five patients (25%), a sharp angle at the entrance to the target vein in seven (35%), a venous valve at the vessel entrance in eight (40%), and, finally, poor support for the guiding catheter in four (20%), due to the presence of either a fenestrated Thebesian valve (two patients) or a restrictive Vieussens valve (two patients) that blocked passage of the guiding catheter or electrode. In four patients (20%), there was more than one factor. In all these cases, implantation was achieved in the target vein without complications after passage of a second hydrophilic guidewire. CONCLUSIONS: The use of a second parallel guidewire (i.e., the double-wire technique) provides a safe and effective way of implanting left ventricular venous pacing electrodes in patients with anatomical complications. PMID- 17338877 TI - [Coauthorship networks and institutional collaboration in Revista Espanola de Cardiologia publications]. AB - INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the patterns of investigator and institutional collaboration in papers published in the Revista Espanola de Cardiologia. METHODS: Details of coauthorship and institutional collaboration involved in articles published in the Revista Espanola de Cardiologia in the period 2000-2005 were recorded and a collaboration index was derived. Collaboration networks were identified using the TextToPajek and PAJEK software tools. RESULTS: Of the 980 papers analyzed, 95.1% had been authored by two or more individuals and 51.43% involved institutional collaboration. The overall collaboration index was 6.23 (standard deviation [SD] 3.1). There was a significant statistical relationship (P< .02) between the collaboration index and the journal section in which the article was published: the Original Articles and Special Reports sections had the highest collaboration indices (mean 7.87 [2.88]; and mean 6.59 [5.02], respectively). The 44 authors who had the highest publication rates were identified. In addition, 25 coauthorship networks involving 112 investigators were observed. CONCLUSIONS: An analysis of collaboration networks led to the identification of a number of author networks in cardiovascular medicine in Spain, and highlighted the interrelationships between them in terms of both scientific research and scientific publications. The most significant aspect of institutional collaboration was the predominance of collaboration within institutions and within Spanish autonomous regions (i.e., 80.57% of collaborations). Possible topics for future study include an analysis of the scientific productivity of the networks identified and of changes in the pattern of collaboration over time. PMID- 17338878 TI - [Influence of measurement duration and frequency on ambulatory blood pressure monitoring]. AB - INTRODUCTION AND OBJECTIVES: Most studies of ambulatory blood pressure monitoring have involved taking measurements every 15-30 minutes over a 24-hour period. We investigated the effect of measurement duration and frequency on the diagnostic blood pressure values obtained by ambulatory monitoring. METHODS: The study involved 1450 hypertensive patients and a control group of 378 normotensive volunteers. Blood pressure was measured at 20-minute intervals from 07:00 to 23:00 and at 30-minute intervals at night for 48 consecutive hours. Data were subdivided in such a way as to generate different series of data that were collected at 1-, 2-, 3-, or 4-hour intervals over the 48-hour period. In addition, two data series at the original measurement frequency were derived for the first and second 24-hour periods. The correspondence between the mean blood pressure values derived from the original data series and those from the different subdivided data series was assessed. RESULTS: Variability in the estimated mean blood pressure increased progressively as the measurement frequency decreased: the error range grew from 11 mmHg for hourly data to 28 mmHg for 4-hourly data. The error range was even greater (i.e., 36 mmHg) for data divided into 24-hour series at the original sampling rate. CONCLUSIONS: This study demonstrates that the reproducibility of mean blood pressure values depends more on measurement duration than measurement frequency. The findings indicate that monitoring blood pressure for only 24 hours may be insufficient for diagnosing hypertension, identifying a dipper circadian pattern, or assessing treatment efficacy. PMID- 17338879 TI - [Comparison of the REGICOR and SCORE function charts for classifying cardiovascular risk and for selecting patients for hypolipidemic or antihypertensive treatment]. AB - INTRODUCTION AND OBJECTIVES: In Spain, use of the Framingham-REGICOR (Registre Gironi del Cor) and SCORE (Systematic Coronary Risk Evaluation) risk charts is recommended for stratifying cardiovascular disease risk. The aims of the present study were to evaluate the degree of agreement between these charts when used to evaluate cardiovascular disease risk in nondiabetic individuals aged 40-65 years and to estimate the percentage of patients recommended for hypolipidemic or antihypertensive treatment. METHODS: The study included 608 nondiabetic patients aged between 40-65 years (mean 52.8 years, 56.7% female) with no evidence of cardiovascular disease who were attending a primary healthcare center between 1990-1994. REGICOR and SCORE equations were used to calculate 10-year cardiovascular disease risks. Patients were classified as high-risk if their risk was > or =10% with REGICOR or > or =5% with SCORE. RESULTS: Some 7.9% of the population was classified as high-risk with REGICOR and 9.2%, with SCORE (P=.41). Only 2.6% and 2.9% (P=.81) of women were classified as high-risk, compared with 14.8% and 17.5% of men, with REGICOR and SCORE, respectively (P=.40). The kappa coefficient was 0.45. According to European professional society guidelines, 23.8% of patients classified by SCORE and 23.0% classified by REGICOR (P=.73) would be recommended hypolipidemic treatment, while 31.2% and 31.7% (P=.85), respectively, would be recommended antihypertensive treatment. CONCLUSIONS: There was moderately good agreement between REGICOR and SCORE charts when used to evaluate nondiabetic individuals aged 40-65 years. They identified similar percentages of patients who would be recommended for hypolipidemic or antihypertensive treatment. PMID- 17338880 TI - [Electrocardiographic criteria for left ventricular hypertrophy and cardiovascular risk in hypertensives. VIIDA study]. AB - INTRODUCTION AND OBJECTIVES: To determine whether Cornell and Sokolow-Lyon criteria identify different groups of patients with left ventricular hypertrophy (LVH), and whether there is a relationship between hypertrophy severity and the prevalence of cardiovascular disease. METHODS: Cross-sectional multicenter study carried out in cardiology departments on hypertensive patients with electrocardiographic LVH, as defined by Cornell or Sokolow-Lyon criteria. Blood pressure (BP) and clinical and laboratory data were recorded. The study population was divided into quartiles according to electrocardiographic findings to enable relationships with cardiovascular disease to be evaluated. RESULTS: Overall, 3074 patients with LVH were studied: 978 (31.8%) met both LVH criteria, 1244 (40.5%) met Cornell criteria only, and 852 (27.7%) met Sokolow-Lyon criteria only. Fulfillment of Sokolow-Lyon criteria was associated with male gender, a low body mass index (BMI), a low prevalence of diabetes, and a high prevalence of myocardial infarction. Fulfillment of Cornell criteria was associated with female gender, a high BMI, and a high prevalence of diabetes. Fulfillment of both criteria was associated with poor BP control and a high prevalence of heart failure. Associations were observed between LVH severity and the prevalence of cardiovascular disease: the adjusted odds ratio for the upper versus the lower quartile was 1.65 (P=.011) for Sokolow-Lyon criteria, 1.59 (P=.014) for Cornell criteria, and 2.03 (P=.001) for both combined. CONCLUSIONS: Sokolow-Lyon and Cornell criteria identify patients with different high-risk cardiovascular risk profiles. Consequently, it would be preferable to use both criteria as this would increase the detection rate of electrocardiographic LVH. Moreover, there is a relationship between the severity of electrocardiographic LVH and the prevalence of established cardiovascular disease. PMID- 17338881 TI - [Socioeconomic pathology as a cause of regional differences in the prevalence of metabolic syndrome and pregnancy-induced hypertension]. AB - The epidemic of cardiovascular disease being experienced by developing countries has resulted in a debate about the possible existence of regional differences in etiology and pathophysiology that could be associated with socio-economic factors. Clear demonstration of these differences is important because there may be a need for different approaches to prevention, diagnosis and treatment. There is some evidence that there are differences between populations in developed and developing countries in the pathophysiologic mechanisms underlying pregnancy induced hypertension and metabolic syndrome, just as there are in the relative weightings of risk factors that predict the appearance of these conditions. Observations in our country suggest that increasing exposure to changes in lifestyle brought about by the consumer society (e.g., a lack of exercise, and a high-fat, high-calorie diet) results in a natural biological response (e.g., obesity, metabolic syndrome, and diabetes) that increases the risk of cardiovascular disease. We propose that the term socioeconomic pathology should be used to describe these changes associated with modern society so that they can be differentiated and considered in isolation from socioeconomic factors and other risk factors. We regard the interaction between these various factors as the most important cause of the rapidly increasing incidence of cardiovascular disease observed in developing countries in recent years. PMID- 17338882 TI - [Non-coronary arterial disease: of intercot to cardiologists?]. PMID- 17338883 TI - [Atherosclerosis as a systemic disease]. AB - Atherosclerosis is a widespread, chronic progressive disease that mainly involves medium-sized arteries. Clinically, it can become apparent as ischemic heart disease, cerebrovascular disease, or peripheral arterial disease. In Spain, atherosclerosis is responsible for 124,000 deaths each year. Despite the trend towards a reduction in the aged-adjusted mortality rate for cardiovascular disease, the public health burden is expected to increase. The risk factors are the same for all affected vascular beds, regardless of location, and can be classified as either causal, conditional or predisposing. The presence of atherosclerosis in a particular vascular bed is frequently associated with disease in other vascular territories. Risk assessment tables, inflammatory markers, imaging, and the ankle-brachial index can help in identifying subclinical atherosclerosis. Given the systemic nature of the disease, treatment with statins, antiplatelet agents and angiotensin-converting enzyme inhibitors have consistently proven beneficial, irrespective of the vascular bed affected. PMID- 17338884 TI - [Multiple rare causes of typical angina pectoris in a single patient]. PMID- 17338885 TI - [Janus tacrolimus-eluting carbostent. Immediate and medium-term clinical results]. AB - This observational and clinical follow-up study involved the first 50 patients who were treated with the Janus tacrolimus-eluting carbostent (Sorin Group) at our hospital. The patients' mean age was 66 (10) years, 38% were diabetic, and 56% were admitted with acute coronary syndrome. In total, 56 lesions were treated (52% were type B2/C), of which 12% involved in-stent restenosis, 5% were chronic occlusions, 23% were long lesions (>20 mm), 25% were in small vessels (< or = 2.5 mm), 7% were aorto-ostial lesions, 5% were in vein grafts, and 14% involved angiographically visible thrombus. Some 63 Janus carbostents were implanted (i.e., 1.26 [0.49] stents/patient). A successful outcome was achieved for all lesions. One patient (2%) required reintervention at the target lesion because of acute thrombosis. During a follow-up period of 10 (3) months, eight (16%) major adverse cardiac events occurred: there was one (2%) death due to heart failure and seven patients (14%) required revascularization, in five (10%) cases because of restenosis of the Janus carbostent. PMID- 17338886 TI - [Intramural aortic hematoma and anticoagulation]. AB - Intramural aortic hematoma is one of a group of conditions covered by the term acute aortic syndrome. Many aspects of its natural history remain poorly understood, and the best treatment is not known. The aim of this study was to describe the clinical and radiological characteristics and follow-up of a group of patients with intramural aortic hematoma who received anticoagulant therapy during hospitalization. We selected a prospective cohort of patients with a diagnosis of intramural aortic hematoma and carried out an analysis of those who received anticoagulation treatment during the acute phase of the illness. Patients received anticoagulation for a range of different reasons. In all patients, the intramural aortic hematoma was observed to undergo gradual regression despite anticoagulation therapy. PMID- 17338887 TI - [Secondary prevention program: impact on cardiovascular risk]. AB - The aims of this study were to determine the effect of a secondary prevention program on the treatment and control of coronary risk factors and to assess whether it improves functional capacity. The study involved 401 patients with coronary heart disease (mean age 57.1 years; 89% men). Clinical and anthropometric data, including blood pressure, were recorded, and electrocardiography, laboratory analysis and exercise testing were performed before and after the program, which lasted 2-3 months. The therapeutic intervention comprised pharmacological treatment of coronary risk factors and the encouragement of life-style changes, including a recommended medically supervised physical exercise regime. By the end of the program, lipid and lipoprotein levels had improved significantly (P< .001 for all). The proportion of smokers decreased from 37.4% to 3.6% (P< .001). Functional capacity increased by 26% (P< .001). In conclusion, patients who took part in the secondary prevention program experienced improvements in cardiovascular risk profile and functional capacity. PMID- 17338888 TI - [Valve repair for bicuspid aortic valve regurgitation: an option?]. AB - Bicuspid aortic valve is the most common form of congenital heart disease. It is associated with both valvular pathology and aortic disease. Aortic regurgitation caused by a bicuspid aortic valve can be corrected by surgical valve repair, which has good short-term results. However, the significant rate of aortic regurgitation recurrence found on long-term follow-up remains a problem, partly because of the progressive aortic dilatation that is characteristic of this disease. We report three different cases of bicuspid aortic valve treated by surgical valve repair at our centre. PMID- 17338889 TI - [Dilated cardiomyopathy in a patient with acromegaly: echocardiographic development after treatment]. PMID- 17338890 TI - [Regression of sick sinus syndrome after treatment of sleep apnea syndrome]. PMID- 17338891 TI - [Cardiac rupture during exercise testing]. PMID- 17338892 TI - [Identification of a cardiac allograft rejection marker using microarray gene expression analysis in lymphocytes from heart transplant patients]. PMID- 17338893 TI - [Postinfarction intramyocardial dissecting hematoma after percutaneous coronary revascularization]. PMID- 17338894 TI - Autoimmunity: a complex and multidisciplinary pathology. PMID- 17338895 TI - Role of viruses and atypical bacteria in asthma exacerbations among children in Oporto (Portugal). AB - BACKGROUND: Upper respiratory tract infections are known to be a significant precipitant of acute asthma exacerbations. The aim of this study was to evaluate seasonal trends and the role of these pathogens in asthma exacerbations in school aged children from Oporto (Portugal). METHODS: Nasal aspirates were collected from children aged 6 to 12 years old with asthma exacerbations attended in the Pediatric Emergency Department one day per week from January 1 to December 31, 2003. Demographic data, severity of asthma and asthma exacerbations, and current treatment were recorded. Samples were obtained through nasal wash with 1 ml saline and were processed by immunofluorescence assays (respiratory syncytial virus, adenovirus, parainfluenza and influenza virus), retrotranscription polymerase chain reaction (rhinovirus) and polymerase chain reaction (enterovirus, Chlamydia pneumoniae and Mycoplasma pneumoniae). RESULTS: In 54 eligible children, 37 nasal samples were obtained. Infectious agents were detected in 78 % of the patients. Rhinovirus was detected in 70.3 %, Mycoplasma pneumoniae in 16.2 %, enterovirus in 10.8 %, and Chlamydia pneumoniae in 2.7 %. Coinfection was identified in 21.6 % of the samples. There was no significant correlation between current treatment status, severity of asthma or exacerbations and the isolated agents. Two distinct peaks of asthma exacerbation were found, 40.5 % in spring and 32.4 % in autumn [corrected] The highest number of cases was recorded in March and the lowest in August and January. Rhinoviruses was detected in 27 % of the cases in autumn and in 24.3 % in spring [corrected] CONCLUSIONS: These results confirm the previously reported high frequency of rhinovirus detection in asthma exacerbations in children and provide evidence that asthma exacerbations and rhinovirus infections follow a seasonal pattern, occurring mostly in spring and autumn. The findings also underscore the frequency of Mycoplasma pneumoniae detection, and emphasize the importance of this agent as a possible trigger of asthma exacerbations. PMID- 17338896 TI - Systemic reactions to wasp sting: is the clinical pattern related to age, sex and atopy? AB - BACKGROUND: The aim of this study was to analyze the frequency of clinical features and the severity of systemic reactions to wasp stings, and to establish their relationship with mean age, sex, and atopy. METHODS: We studied 115 patients who suffered an anaphylactic reaction to wasp sting and showed specific IgE to venoms from Vespula and/or Polistes. In all patients, age, sex and personal history of atopy were registered. Cutaneous, respiratory, cardiovascular and gastrointestinal involvement during the course of the reaction was investigated. Each patient was assigned a severity grade according to a simple two-grade classification based on Muller's criteria. Bivariable analysis was performed to analyze the associations among mean age, sex and atopy and the symptoms and severity of the reaction. RESULTS: The mean age was 40.2 years. There were 60 males (52.2 %) and 55 females (47.8 %). Twenty-six patients (22.6 %) were atopic. The percentages of involved systems were as follows: skin 90.4 %, respiratory 54.8 %, cardiovascular 33.9 %, and gastrointestinal 21.7 %. Reactions were mild in 40.8 %, and severe in 59.1 %. The mean age was higher in patients without cutaneous symptoms (p < 0.05). Cardiovascular involvement was more frequent in males (p < 0.05). No other significant differences were found. CONCLUSION: The symptoms of systemic reactions to wasp venom most frequently involved the skin, while reactions without cutaneous involvement were more frequent in older patients. Cardiovascular involvement was more common in males. The clinical pattern was not determined by atopy and the variables studied were not related to severity. PMID- 17338897 TI - Sensitization in early age to food allergens in children with atopic dermatitis. AB - BACKGROUND: Clinical and laboratory evidence increasingly supports the notion that food allergy plays a role in the pathogenesis of atopic dermatitis (AD). However, the prevalence of clinically significant food hypersensitivity among children with AD remains an unanswered question. OBJECTIVE: To prospectively determine the prevalence of IgE-mediated food hypersensitivity among patients referred to a dermatology department for evaluation of AD, and to analyze the clinical relevance of these sensitizations in AD. METHODS: We studied 44 infants of both sexes, aged less than 12 months old, who attended the dermatology department with symptoms of AD. Compliance with Hanifin-Rajka criteria was confirmed and the severity of AD was evaluated using the SCORAD index. IgE mediated sensitization to cow's milk, alpha-lactalbumin, beta-lactoglobulin, casein, egg-white, egg-albumin, ovomucoid and foods introduced into the diet was studied using the skin prick test (SPT) and measurement of specific serum IgE (sIgE) by CAP System fluorescein-enzyme immunoassay. Cow's milk, as well as suspected foods from the clinical history or those with a positive SPT and/or sIgE, were withdrawn from the diet to evaluate improvement in AD, and an open controlled challenge test was carried out. RESULTS: Of the 44 patients studied, sensitization to foods was detected in 27 (61 %). No changes were observed in AD during the elimination diet or when the eliminated foods were subsequently reintroduced into the diet. The results of open controlled food challenges were positive in 12 patients (27 %). CONCLUSIONS: A high prevalence of food sensitization was found in infants with AD. The most frequent sensitization observed was to egg, although with little clinical relevance since this food had not been introduced into the diet. In the sample studied, the clinical relevance of the observed food hypersensitivities was confirmed in relation to AD. Further studies are required to confirm these results. PMID- 17338898 TI - Skin prick test results of child patients diagnosed with bronchial asthma. AB - BACKGROUND: The pathogenesis of asthma is associated with both genetic and environmental factors. Allergen sensitization is an important risk factor in asthma development. AIM: To evaluate sensitivity to allergens by using the skin prick test in patients with a diagnosis of bronchial asthma. METHOD: Patients with a diagnosis of bronchial asthma followed-up at the Ministry of Health, Diskapi Children's Diseases Training and Research Hospital in Ankara (Turkey) between January 1995 and March 2000 were included. Sensitivity to allergens, as determined by the skin prick test, was evaluated retrospectively. RESULTS: The files of a total of 3025 children (63.3 % boys) with bronchial asthma, aged 3 months to 16 years were evaluated. Of the total, 1667 patients with a diagnosis of bronchial asthma and 1358 with bronchial asthma plus allergic rhinitis were under follow-up. Of the 3025 asthmatic patients, 1902 had undergone the skin prick test and 60.3 % of these patients were atopic. The most common allergens were house dust mite [726 patients (63.3 %)], followed by pollens [565 patients (49.3 %)]. The most common allergen within this group was grass pollens [348 patients (30.3 %)]. CONCLUSIONS: Atopy was an important risk factor in our patients and the most common allergens were aeroallegens. The development of sensitization could be delayed by early precautions. PMID- 17338899 TI - Once versus twice daily budesonide metered-dose inhaler in children with mild to moderate asthma: effect on symptoms and bronchial responsiveness. AB - BACKGROUND: Simplifying dosing regimens could improve both adherence and asthma related morbidity. However, there is little information on the effectiveness of once-daily budesonide, administered through a metered dose inhaler (MDI) plus spacer, on asthma symptoms and pulmonary function in asthmatic children. METHODS: The aim of this study was to compare the effect of once-daily versus twice-daily doses of inhaled budesonide on symptoms, lung function and bronchial hyperresponsiveness (BHR) in asthmatic children. This study was a randomized, single-blind, parallel clinical trial. Patients received budesonide from an MDI either 800 microg as a daily dose or fractionated in 400 microg twice a day for 12 weeks. Statistical analysis was performed using tests for independent and paired samples. RESULTS: In both groups, asthma symptoms significantly decreased. However, the improvement in asthma symptoms, decrease in BHR and treatment adherence were significantly greater in the once-daily group than in the twice daily group (p < 0.05). No significant differences were found between the two groups in spirometric parameters, morning peak expiratory flow or plasma cortisol values. CONCLUSIONS: Once-daily administration of 800 microg of inhaled budesonide administered by MDI plus spacer was more effective in controlling symptoms and improving BHR than fractionating the dose to 400 microg twice daily. The differences observed in this study could have been due to the greater adherence to treatment in patients in the once-daily group. PMID- 17338900 TI - Sarcoidosis following specific immunotherapy: more than just coincidence? AB - Although not yet clear, the etiology of sarcoidosis may be linked to seasonal, environmental and genetic factors; mycobacterial or other infections. To the best of our knowledge there is no data suggesting any connection between the onset of sarcoidosis and specific allergen immunotherapy in the medical literature. During the 11-year period between 1993 and 2005, a total of 91 sarcoidosis cases have been diagnosed at our institution. Out of these, here we present 3 cases of de novo sarcoidosis occurring after receiving specific immunotherapy (SIT) at the same institution (two of which had acquired the disease in Sweden where they had resided for a short time). We suggest that sarcoidosis may occur in patients following (SIT) probably via an abnormal immunological host response to an unknown antigenic trigger. PMID- 17338901 TI - Polysensitization to aeroallergens and food in eosinophilic esophagitis in a pediatric population. AB - There are few studies on eosinophilic esophagitis (EE) in the pediatric population in Europe. We present our data and emphasize the following findings: a) all patients had symptoms of allergic respiratory disease prior to receiving a diagnosis of EE with polysensitization (aeroallergens, food allergens); and b) in contrast with the results of earlier studies, food sensitization in our series most often corresponded to legumes. PMID- 17338902 TI - Urticaria due to calcium pidolate. AB - Calcium salts are often prescribed in the prevention and treatment of osteoporosis. Adverse reactions have been described, mostly concerning to the gastrointestinal tract, parathyroid glands and bone resorption. We report the case of a 52-year-old woman who started treatment with 500 mg per day of calcium pidolate. 90 minutes after the intake of the second dose, she experienced an itchy maculopapular eruption. Skin Prick Tests were carried out with the implicated drug and calcium-carbonate and they both were negatives. An oral challenge-test with 500 mg of calcium-pidolate was ruled out. 60 minutes later, the patient responded positively when she experienced a similar reaction with erythematous and itchy papulae on the trunk and the neck. Finally, an oral challenge-test with 500 mg calcium-carbonate was performed with good tolerance. To the best of our knowledge, this is the first documented case of allergy to calcium-pidolate with tolerance to other calcium salt. PMID- 17338903 TI - Defining the neural circuitry of depression: toward a new nosology with therapeutic implications. PMID- 17338904 TI - Attention bias to threat faces in children with bipolar disorder and comorbid lifetime anxiety disorders. AB - BACKGROUND: Although comorbid anxiety disorders are common in children with bipolar disorder (BD), it is unclear how this comorbidity impacts the pathophysiology of the illness. METHODS: Pediatric BD with lifetime anxiety (BD+ANX, n = 20), BD without lifetime anxiety (BD-ANX, n = 11), and controls (n = 14) were administered the visual-probe paradigm, which assesses attention bias to threat faces. RESULTS: Bipolar disorder +ANX demonstrated a stronger bias toward threat relative to BD-ANX and controls; the latter two did not differ from each other. CONCLUSIONS: Bipolar disorder +ANX showed a bias toward threat while, in two previous studies, anxious children showed a bias away from threat faces. Future studies should compare the pathophysiology of BD with and without a comorbid anxiety disorder and anxiety disorders presenting alone. PMID- 17338905 TI - Evolution of peri-operative care of patients. PMID- 17338906 TI - Peri-operative blood management in elective orthopaedic surgery. A critical review of the literature. AB - Blood loss during orthopaedic procedures can be extensive and the need for allogeneic blood is a common requirement. However, blood transfusion conceals a number of well-recognised risks and complications and blood products have become more expensive because of their specific preparation procedure. Surgical technique, awareness of the problem and restriction of transfusion triggers are important factors affecting the management of blood loss. Several studies have additionally shown the efficacy of epoetin injections in increasing the pre operative haemoglobin level. On the other hand, the true benefit of pre-operative autologous donation, acute normovolemic haemodilution and COX-2 selective NSAIDs remains under dispute. Regarding the role of platelet rich plasmapheresis, fibrin sealing and anti-fibinolytic drugs more data are needed. Hypotensive epidural anaesthesia seems to be an advantageous method in minimising peri-operative blood loss. However, this is not a widely performed technique in orthopaedic surgery. In addition, post-operative blood cell saving systems after total knee or hip arthroplasty have been reported to significantly minimise allogeneic blood transfusions when compared to control groups. It can be concluded that many interventions diminish more or less allogeneic blood transfusion in elective orthopaedic surgery. Nevertheless more prospective studies are needed and appropriate algorithms should be applied in peri-operative blood loss management. This review presents an overview of the available interventions which aim to diminish the use of allogeneic blood in elective orthopaedic surgery. PMID- 17338907 TI - Is minimally invasive surgery less invasive in total hip replacement? A pilot study. AB - It has been suggested that minimally invasive surgery (MIS) in total hip replacement (THR) is less traumatic than standard techniques. This study was designed to address the question of whether an anterior MIS approach generates less inflammation and muscle damage than the standard posterolateral (PL) approach. Inflammation parameters such as interleukin-6 (IL-6), muscle damage parameters like heart type fatty acid binding protein (H-FABP), and haemoglobin (Hb) levels were determined pre-operatively and at five consecutive points post operatively in 10 patients operated through a MIS anterior approach and in 10 patients operated through a PL approach. The mean IL-6 concentration increased from 3 pg/ml in both groups pre-operatively to 78.5 pg/ml (PL group) vs 74.8 pg/ml (MIS group) at 6 hours post-operatively and reached a maximum of 100 pg/ml (PL group) vs 90.5 pg/ml pg/ml (MIS group) after 24 hours. Up to this time point, there was a decrease in both groups. The post-operative mean H-FABP concentration increased to 10.7 microg/l in the PL group vs 15.8 microg/l in the MIS group. It formed a plateau and decreased after 24 hours post-operatively. The Hb levels were 14.5 g/dl before surgery and decreased to 10.7 g/dl (PL group) and 10.0 g/dl (MIS group) at 72 hours post-operatively. No significant differences were found between the two approaches either in inflammation and muscle damage or blood loss. Although the absence of a learning curve may explain the lack of a difference between both techniques, we speculate that the term MIS is at least doubtful in terms of being less traumatic. PMID- 17338908 TI - Minimally invasive technique in total knee arthroplasty--history, tips, tricks and pitfalls. AB - Minimally invasive surgery (MIS) in Total Knee Arthroplasty (TKA) has been evolving since the early 1990s and was first described by several authors from the USA in early 2003-4. The evolution was driven from patients and clinicians alike and the technique has been used by several experienced knee surgeons worldwide. Although the procedure is demanding and the learning curve long, the benefits outweigh the difficulties faced during the learning process. Our experience with minimally invasive techniques started in 2003. At the beginning only a few procedures were carried out as rigorous exclusion criteria were applied. However, as confidence grew the number of operations has significantly increased. The average surgical time for minimally invasive technique is longer than for the standard technique, particularly in the early stages. More attention needs to be paid to the alignment, sizing and positioning of the prosthesis. According to our early experience, functional recovery is faster with MIS compared with standard technique. The MIS group achieved better knee flexion during the first three months (average of 116 degrees ) compared to open access surgery (average of 97 degrees ). There was no significant difference in alignment and component sizing between the two groups. PMID- 17338909 TI - Surgical stress response. AB - Recent advances in molecular medicine have allowed the characterization and quantification of inflammatory cascades following surgery and trauma. Activation of immune cells is followed by the release of various cytokines as well as by migration of leukocytes into inflamed tissues. Various methods have been developed in order to modulate the immune-inflammatory system and at the same time to prevent overreaction and unexpected complications. In this context, the magnitude of surgical stress exerted on the patient is of paramount importance. Several factors, either controllable or not, are known to contribute to the development and amplification of the 'surgical stress response'. Therefore, they should be taken into consideration by both surgical practitioners and other medical specialties involved in the management of the traumatised patient. PMID- 17338910 TI - Fast track in total hip and knee arthroplasty--experiences from Hvidovre University Hospital, Denmark. AB - This study investigated whether unselected patients operated on with total hip arthroplasty (THA) or total knee arthroplasty (TKA) could accomplish a self developed accelerated track, ANORAK-HH, with a planned length of stay (LOS) of maximum 5 days and patient satisfaction at all parts of the track. 307 patients who sustained 329 hip and knee arthroplasties were included in the study with the main material constituted from 243 primary unilateral THA and TKA arthroplasties. ANORAK-HH includes pre-operative patient clinic, patient motivation, dedicated staff, unchanged criteria for discharge and a planned LOS of maximum 5 days. 22 patient characteristics and 11 satisfaction parameters were registered as well as readmissions within 3 months. 95% of patients had a LOS of maximum 5 days with a mean of 3.9 days. Median and mean values of satisfaction for the entire track were 10 and 9.4 out of 10, respectively. Participation in patient clinic did not influence LOS or satisfaction. Operations at the beginning of the week and lack of blood transfusion were associated with shorter LOS. Finally, ANORAK-HH could be effectively accomplished in unselected THA and TKA patients without having an adverse effect on patient readmission rate. PMID- 17338911 TI - Experience in the first four years of rapid recovery; is it safe? AB - The average length of hospital stay after Total Hip Replacement (THR) has been decreasing over time. Recently, many hospitals have commenced rapid recovery programs such as Joint Care. In Joint Care the patients are usually discharged on the fifth post-operative day with relatively fresh surgical wounds. The aim of this study is to evaluate the Joint Care program after THR. Between February 2000 and February 2004, the Joint Care program was used in 611 patients after THR. The average age of the patients was 66.3 yrs (SD 9.3; range 24-86 yrs) and 68% (n= 415) of them were female. All clinical and outpatient charts as well as nursery records were evaluated. The follow up was from 6 months to 4 years (average: 2.5 years). At the planned fifth post-operative day, 92% (n = 562) of patients were discharged from hospital (SD 1.7 days; range 6-25 days). 3.8% (n= 23) of the remaining cases faced wound problems--prolonged wound drainage in 2.3% (n = 14) and potential superficial infection in 1.5% (n = 9) - causing a delay in their discharge. The readmission rate was 6.4% (n = 39) due to hip dislocation (3.4%; n = 21), re-evaluation of wound (1.5%; n= 9), deep infection (1.2%; n = 7)) and cardiac events (0.3%; n = 2). All the infection cases were treated effectively with debridement and antibiotics and no revision for any reason was reported. The Joint Care program seems to be effective after THR. Post-operative hip dislocation was the main reason for post-operative readmission. However, no clear signs that the intensive rehabilitation program caused more complications compared to previous regimens were evident. The above results encourage the application of rapid recovery programs in Orthopaedic surgery and joint replacement. PMID- 17338912 TI - Role of physiotherapy in peri-operative management in total knee and hip surgery. AB - Knee osteoarthritis (OA) is often associated with pain, functional impairment and various degrees of disability. Physiotherapy in combination with both aerobic and strength training exercises have shown positive effects in both the pre-operative and post-operative period. At the initial stages of osteoarthritis, physical therapy and education can improve the functional outcome and the participation of patients in daily activities. In the case of OA progression and when an operation is the only effective treatment, physiotherapy is very useful in enhancing self esteem and minimising depression and anxiety for the forthcoming surgery. Post operative intense physical therapy and Continuous Passive Motion (CPM) application offer remarkable benefits in terms of faster recovery, shorter hospital stay and increase of range of motion. Furthermore, home-based excercises following discharge from the hospital should be encouraged in order to optimise the final result. Although the entire mechanism remains unclear, physical exercise protocols may be beneficial for patients and the health system alike. PMID- 17338913 TI - Contribution of membrane mucins to tumor progression through modulation of cellular growth signaling pathways. AB - Mucins are large, heavily O-glycosylated proteins expressed by epithelial tissues. The canonical function of membrane mucins is to provide protection to vulnerable epithelia by forming a steric barrier against assault, and by contributing to the formation of protective extracellular mucin gels. The aberrant overexpression of mucins is thought to contribute to tumor progression by allowing tumor cells to evade immune recognition, and by aiding in the breakdown of cell-cell and cell-matrix contacts to facilitate migration and metastasis. Recent evidence suggests that we should now modify our thinking about mucin function by considering their roles in signaling pathways leading to cellular growth control. Here we review the markedly divergent mechanisms by which membrane mucins, specifically MUC1 and MUC4, influence pathways contributing to cellular proliferation and survival. The cytoplasmic domain of MUC1 serves as a scaffold for the assembly of a variety of signaling proteins, while MUC4 influences the trafficking and localization of growth factor receptors, and hence their responses to external stimuli. We also discuss how tumor cells exploit these mechanisms to promote their own growth and metastasis. PMID- 17338915 TI - Advances in defining regulators of cementum development and periodontal regeneration. AB - Substantial advancements have been made in defining the cells and molecular signals that guide tooth crown morphogenesis and development. As a result, very encouraging progress has been made in regenerating crown tissues by using dental stem cells and recombining epithelial and mesenchymal tissues of specific developmental ages. To date, attempts to regenerate a complete tooth, including the critical periodontal tissues of the tooth root, have not been successful. This may be in part due to a lesser degree of understanding of the events leading to the initiation and development of root and periodontal tissues. Controversies still exist regarding the formation of periodontal tissues, including the origins and contributions of cells, the cues that direct root development, and the potential of these factors to direct regeneration of periodontal tissues when they are lost to disease. In recent years, great strides have been made in beginning to identify and characterize factors contributing to formation of the root and surrounding tissues, that is, cementum, periodontal ligament, and alveolar bone. This review focuses on the most exciting and important developments over the last 5 years toward defining the regulators of tooth root and periodontal tissue development, with special focus on cementogenesis and the potential for applying this knowledge toward developing regenerative therapies. Cells, genes, and proteins regulating root development are reviewed in a question answer format in order to highlight areas of progress as well as areas of remaining uncertainty that warrant further study. PMID- 17338914 TI - Regulation of the epithelial Na+ channel by peptidases. AB - Recent investigations point to an important role for peptidases in regulating transcellular ion transport by the epithelial Na(+) channel, ENaC. Several peptidases, including furins and proteasomal hydrolases, modulate ENaC maturation and disposal. More idiosyncratically, apical Na(+) transport by ENaC in polarized epithelia of kidney, airway, and gut is stimulated constitutively by one or more trypsin-family serine peptidases, as revealed by inhibition of amiloride sensitive Na(+) transport by broad-spectrum antipeptidases, including aprotinin and bikunin/SPINT2. In vitro, the transporting activity of aprotinin-suppressed ENaC can be restored by exposure to trypsin. The prototypical channel-activating peptidase (CAP) is a type 1 membrane-anchored tryptic peptidase first identified in Xenopus kidney cells. Frog CAP1 strongly upregulates Na(+) transport when coexpressed with ENaC in oocytes. The amphibian enzyme's apparent mammalian orthologue is prostasin, otherwise known as CAP1, which is coexpressed with ENaC in a variety of epithelia. In airway cells, prostasin is the major basal regulator of ENaC activity, as suggested by inhibition and knockdown experiments. Other candidate regulators of mature ENaC include CAP2/TMPRSS4 and CAP3/matriptase (also known as membrane-type serine protease 1/ST14). Mammalian CAPs are potential targets for treatment of ENaC-mediated Na(+) hyperabsorption by the airway in cystic fibrosis (CF) and by the kidney in hypertension. CAPs can be important for mammalian development, as indicated by embryonic lethality in mice with null mutations of CAP1/prostasin. Mice with selectively knocked out expression of CAP1/prostasin in the epidermis and mice with globally knocked out expression of CAP3/matriptase exhibit phenotypically similar defects in skin barrier function and neonatal death from dehydration. In rats, transgenic overexpression of human prostasin disturbs salt balance and causes hypertension. Thus, several converging lines of evidence indicate that ENaC function is regulated by peptidases, and that such regulation is critical for embryonic development and adult function of organs such as skin, kidney, and lung. PMID- 17338916 TI - Anabolic agents and the bone morphogenetic protein pathway. AB - A major unmet need in the medical field today is the availability of suitable treatments for the ever-increasing incidence of osteoporosis and the treatment of bone deficit conditions. Although therapies exist which prevent bone loss, the options are extremely limited for patients once a substantial loss of skeletal bone mass has occurred. Patients who have reduced bone mass are predisposed to fractures and further morbidity. The FDA recently approved PTH (1-34) (Teriparatide) for the treatment of postmenopausal osteoporosis after both preclinical animal and clinical human studies indicated it induces bone formation. This is the only approved bone anabolic agent available but unfortunately it has limited use, it is relatively expensive and difficult to administer. Consequently, the discovery of low cost orally available bone anabolic agents is critical for the future treatment of bone loss conditions. The intricate process of bone formation is co-ordinated by the action of many different bone growth factors, some stored in bone matrix and others released into the bone microenvironment from surrounding cells. Although all these factors play important roles, the bone morphogenetic proteins (BMPs) clearly play a central role in both bone cartilage formation and repair. Recent research into the regulation of the BMP pathway has led to the discovery of a number of small molecular weight compounds as candidate bone anabolic agents. These agents may usher in a new wave of more innovative and versatile treatments for osteoporosis as well as orthopedic and dental indications. PMID- 17338917 TI - The role of mammalian circadian proteins in normal physiology and genotoxic stress responses. AB - The last two decades have significantly advanced our understanding of the organization of the circadian system at all levels of regulation-molecular, cellular, tissue, and systemic. It has been recognized that the circadian system represents a complex temporal regulatory network, which plays an important role in synchronizing various biological processes within an organism and coordinating them with the environment. It is believed that deregulation of this synchronization may result in the development of various pathologies. However, recent studies using various circadian mutant mouse models have demonstrated that at least some of the components of the molecular oscillator are actively involved in physiological processes not directly related to their role in the circadian clock. The growing amount of evidence suggests that, in addition to their circadian function, circadian proteins are important in maintaining tissue homeostasis under normal and stress conditions. In this chapter, we will summarize recent data about the regulation of the mammalian molecular circadian oscillator and will focus on a new role of the circadian system and individual circadian proteins in the organism's physiology and response to genotoxic stress in connection with diseases treatment and prevention. PMID- 17338918 TI - Autophagy and cell death. AB - Autophagy is a physiological and evolutionarily conserved phenomenon maintaining homeostatic functions like protein degradation and organelle turnover. It is rapidly upregulated under conditions leading to cellular stress, such as nutrient or growth factor deprivation, providing an alternative source of intracellular building blocks and substrates for energy generation to enable continuous cell survival. Yet accumulating data provide evidence that the autophagic machinery can be also recruited to kill cells under certain conditions generating a caspase independent form of programed cell death (PCD), named autophagic cell death. Due to increasing interest in nonapoptotic PCD forms and the development of mammalian genetic tools to study autophagy, autophagic cell death has achieved major prominence, and is recognized now as a legitimate alternative death pathway to apoptosis. This chapter aims at summarizing the recent data in the field of autophagy signaling and autophagic cell death. PMID- 17338919 TI - Mechanism of depolymerization and severing of actin filaments and its significance in cytoskeletal dynamics. AB - The actin cytoskeleton is one of the major structural components of the cell. It often undergoes rapid reorganization and plays crucial roles in a number of dynamic cellular processes, including cell migration, cytokinesis, membrane trafficking, and morphogenesis. Actin monomers are polymerized into filaments under physiological conditions, but spontaneous depolymerization is too slow to maintain the fast actin filament dynamics observed in vivo. Gelsolin, actin depolymerizing factor (ADF)/cofilin, and several other actin severing/depolymerizing proteins can enhance disassembly of actin filaments and promote reorganization of the actin cytoskeleton. This review presents advances as well as a historical overview of studies on the biochemical activities and cellular functions of actin-severing/depolymerizing proteins. PMID- 17338920 TI - Biology of polycomb and trithorax group proteins. AB - Cellular phenotypes can be ascribed to different patterns of gene expression. Epigenetic mechanisms control the generation of different phenotypes from the same genotype. Thus differentiation is basically a process driven by changes in gene activity during development, often in response to transient factors or environmental stimuli. To keep the specific characteristics of cell types, tissue specific gene expression patterns must be transmitted stably from one cell to the daughter cells, also in the absence of the early-acting determination factors. This heritability of patterns of active and inactive genes is enabled by epigenetic mechanisms that create a layer of information on top of the DNA sequence that ensures mitotic and sometimes also meiotic transmission of expression patterns. The proteins of the Polycomb and Trithorax group comprise such a cellular memory mechanism that preserves gene expression patterns through many rounds of cell division. This review provides an overview of the genetics and molecular biology of these maintenance proteins, concentrating mainly on mechanisms of Polycomb group-mediated repression. PMID- 17338921 TI - Cell and molecular biology of transthyretin and thyroid hormones. AB - Advances in four areas of transthyretin (TTR) research result in this being a timely review. Developmental studies have revealed that TTR is synthesized in all classes of vertebrates during development. This leads to a new hypothesis on selection pressure for hepatic TTR synthesis during development only, changing the previous hypotheses from "onset" of hepatic TTR synthesis in adulthood to "maintaining" hepatic TTR synthesis into adulthood. Evolutionary studies have revealed the existence of TTR-like proteins (TLPs) in nonvertebrate species and elucidated some of their functions. Consequently, TTR is an excellent model for the study of the evolution of protein structure, function, and localization. Studies of human diseases have demonstrated that TTR in the cerebrospinal fluid can form amyloid, but more recently there has been recognition of the roles of TTR in depression and Alzheimer's disease. Furthermore, amyloid mutations in human TTR that are the normal residues in other species result in cardiac deposition of TTR amyloid in humans. Finally, a revised model for TTR-thyroxine entry into the cerebrospinal fluid via the choroid plexus, based on data from studies in TTR null mice, is presented. This review concentrates on TTR and its thyroid hormone binding, in development and during evolution, and summarizes what is currently known about TLPs and the role of TTR in diseases affecting the brain. PMID- 17338922 TI - Development and role of tight junctions in the retinal pigment epithelium. AB - The outer blood-retinal barrier is formed by the retinal pigment epithelium. In any epithelial monolayer, the tight junctions enable the epithelium to form a barrier by joining neighboring cells together and regulating transepithelial diffusion through the paracellular spaces. Tight junctions are complex, dynamic structures that regulate cell proliferation, polarity, and paracellular diffusion. The specific properties of tight junctions vary among epithelia, according to the physiological role of the epithelium. Unlike other epithelia, the apical surface of the retinal pigment epithelium interacts with a solid tissue, the neural retina. Secretions of the developing neural retina regulate the assembly, maturation, and tissue-specific properties of these tight junctions. The slow time course of development allows investigators to dissect the mechanisms of junction assembly and function. These studies are aided by culture systems that model different stages of development. PMID- 17338925 TI - Epidemiology of pulmonary arterial hypertension. AB - Progress in understanding the basic biology and the development of new therapies for pulmonary arterial hypertension have led to improvements in survival. This article reviews clinically important changes in the classification of the pulmonary hypertensive diseases, as well as the epidemiology of various forms of pulmonary hypertension. The risk factors for the development of pulmonary arterial hypertension, prognostic markers, and the effects of current therapies on survival are discussed. PMID- 17338926 TI - Pathology of pulmonary hypertension. AB - The secondary role of pathology in the present clinical management of pulmonary hypertension (PH) reflects to some extent the limitations of the current understanding of the disease. Ample room exists for the diagnostic translation of the pathobiologic studies, with the goal of improving the diagnostic and prognostic power of the pathologic assessment of pulmonary vascular remodeling. This article seeks to show the complementarities of the pathology and pathobiology of PH. PMID- 17338928 TI - Diagnosis of pulmonary arterial hypertension. AB - Accurate diagnosis of pulmonary arterial hypertension is a challenging and complex process that requires a high index of clinical suspicion from even the most astute clinician. This article discusses the use of a variety of noninvasive tests that can help define the population of patients in whom invasive cardiac catheterization should be pursued. It points out the vagaries and limitations of electrocardiography and the radiographic and echocardiographic clues to the diagnosis. Ultimately, right- and, often, concomitant left-heart catheterization is required to establish the diagnosis and distinguish pulmonary arterial hypertension from pulmonary venous hypertension. PMID- 17338927 TI - Genetics and mediators in pulmonary arterial hypertension. AB - Pulmonary arterial hypertension (PAH) is an uncommon disorder of the pulmonary vasculature characterized by remodeling of the smallest pulmonary arteries, leading to a progressive increase in pulmonary vascular resistance. Various forms of PAH exist, including familial (FPAH) and idiopathic (IPAH) forms and associated conditions. FPAH transmits as an autosomal dominant trait that exhibits genetic anticipation but also markedly reduced penetrance (20%). The primary genetic defect of FPAH, identifiable in more than 70% of cases of FPAH, is a mutation in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2), a member of the transforming growth factor beta superfamily. The true prevalence of BMPR2 mutations in IPAH is unknown, with reports ranging from 10% to 40% of patients. The cause of the variable phenotypic expression of PAH among carriers of mutated BMPR2 genes and patients is unclear, and likely related to environmental and genetic modifiers of disease not yet fully elucidated. Although BMPR2-related pathways seem to be pivotal, many other mediator pathways participate in the pathogenesis of different forms of PAH and are being actively investigated, both independently and in combination. As understanding of the molecular basis of this devastating disease improves, opportunities for earlier diagnosis, additional therapeutic regimens, and perhaps disease prevention will emerge. PMID- 17338930 TI - Standard therapies for pulmonary arterial hypertension. AB - After half a century of clinical experience and research, management of pulmonary arterial hypertension remains a challenge. Currently, data to support the use of standard therapies for pulmonary arterial hypertension (oxygen supplementation, diuretics, digoxin, anticoagulation, and calcium channel blockers) are mostly retrospective, uncontrolled prospective, or derived from other diseases with similar but not identical manifestations. In the absence of any further prospective, controlled studies, it is reasonable to use these therapies when they are tolerated. When these therapies are poorly tolerated, however, the threshold for discontinuation should be low. PMID- 17338929 TI - Surrogate end points in pulmonary arterial hypertension: assessing the response to therapy. AB - Recent discoveries in the disease pathophysiology of pulmonary arterial hypertension have been translated into effective therapies tested in clinical trials. The studies have focused on surrogate and intermediate end points, thought to reflect quantity and quality of life, respectively. The authors present the necessary requirements for establishing the reliability and validity of such end points before they may be used dependably. The authors also review the available data, strengths, and weaknesses of potential end points in pulmonary arterial hypertension. PMID- 17338931 TI - Endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. AB - The recognition that endothelin-1 contributes to the pathogenesis of pulmonary arterial hypertension has led to the development of clinically useful endothelin receptor antagonists that improve symptoms and functional capacity and alter the natural history of the disease in a beneficial way. The antagonists have varying degrees of selectivity for the two classes of endothelin receptor, termed ETA and ETB, and the varying degrees may translate into clinical differences. Endothelin receptor antagonists have become an integral part of therapy for pulmonary arterial hypertension, and the indications for their use are expanding. PMID- 17338932 TI - Prostanoid therapy for pulmonary arterial hypertension. AB - Epoprostenol and the structurally related compounds treprostinil, iloprost, and beraprost are collectively referred to as prostanoids. The discovery of epoprostenol in 1976 and unequivocal demonstration of its efficacy in 1996 dramatically altered the approach to therapy for pulmonary arterial hypertension (PAH). Development of prostanoids available through multiple routes of administration and the discovery and development of other agents acting through alternative pathways continue to expand the array of therapeutic options. The use of prostanoids in combination with other PAH drugs and for treating pulmonary hypertensive disorders outside of the PAH classification are areas of ongoing research. PMID- 17338933 TI - The nitric oxide/cGMP signaling pathway in pulmonary hypertension. AB - This article briefly reviews the background of endothelium-dependent vasorelaxation, describes the nitric oxide/cGMP/protein kinase pathway and its role in modulating pulmonary vascular tone and remodeling, and describes three approaches that target the nitric oxide/cGMP pathway in the treatment of patients with pulmonary arterial hypertension. PMID- 17338935 TI - Surgical therapies for pulmonary arterial hypertension. AB - Surgical therapies for the treatment of pulmonary arterial hypertension typically are reserved for patients who are deemed to be refractory to medical therapy and have evidence of progressive right-sided heart failure. Atrial septostomy, a primarily palliative procedure, may stave off hemodynamic collapse from right sided heart failure long enough to permit a more definitive surgical treatment such as lung or combined heart-lung transplantation. This article discusses indications for and results of atrial septostomy and lung and heart-lung transplantation in patients who have pulmonary arterial hypertension. PMID- 17338934 TI - Combination therapy and new types of agents for pulmonary arterial hypertension. AB - This review assesses the available evidence supporting the use of drug combinations for the management of the various forms of pulmonary arterial hypertension (PAH). Ongoing and forthcoming randomized trials evaluating this strategy are also highlighted. Furthermore, new types of agents to treat PAH in the future are explored. PMID- 17338936 TI - Portopulmonary hypertension. AB - As a result of the success of orthotopic liver transplantation, there has been increasing interest in the diagnosis and therapeutic options for the pulmonary vascular complications of hepatic disease. These pulmonary vascular complications range from the hepatopulmonary syndrome, which is characterized by intrapulmonary vascular dilatations, to portopulmonary hypertension (POPH), which is characterized by an elevated pulmonary vascular resistance as a consequence of obstruction to pulmonary arterial blood flow. This review concentrates on POPH. PMID- 17338937 TI - Pulmonary hypertension associated with chronic respiratory disease. AB - Pulmonary hypertension (PH) has long been recognized as a complication of chronic respiratory disease. Recent studies have highlighted the adverse impact PH has on the clinical course of these conditions and have cast doubt on the role of hypoxia in their pathogenesis. Clinicians should carefully consider the possibility of PH during the diagnostic evaluation of chronic respiratory disorders. The usefulness of pharmacologic therapy directed toward PH remains to be determined. PMID- 17338938 TI - Pulmonary hypertension associated with left-sided heart disease. AB - Pulmonary hypertension (PH) denotes a poor prognosis in patients with left-sided heart disease. No study has demonstrated long-term benefit from PH drugs such as prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors. In some cases, cautious use of PH drugs may be indicated. However, theoretic and practical concerns limit any formal recommendations. PMID- 17338939 TI - Congenital heart disease associated pulmonary arterial hypertension. AB - Pulmonary arterial hypertension associated with congenital heart disease, although common (15%-30%) in all-comers with congenital heart disease, is variable in terms of clinical manifestations, severity of associated pulmonary arterial hypertension, and response to therapy and outcomes (depending on lesion anatomy, pulmonary circulation flows and pressures, and presence and timings of surgeries). Evaluation includes imaging and catheterization. Surgical or another anatomic correction may be desirable after rigorous preinterventional assessment. Patients who are not surgical candidates or who fail to improve early or late after surgery may have the potential to respond to idiopathic pulmonary arterial hypertension therapies. Lung or heart/lung transplantation remains an option for selected recalcitrant patients. PMID- 17338940 TI - Chronic thromboembolic pulmonary hypertension. AB - The description of organized thrombus in major pulmonary arteries can be found in autopsy reports dating back to the late nineteenth and early twentieth centuries. Not until the 1950s was the antemortem diagnosis and clinical syndrome of chronic thrombotic obstruction of the major pulmonary arteries better characterized. The first surgical attempt to remove the adherent thrombus from the vessel wall occurred in 1958. This operation provided the conceptual foundation for the distinction between acute and chronic thromboembolic disease of the pulmonary vascular bed, and established that an endarterectomy, and not an embolectomy, would be necessary if a surgical remedy for this disease was to be successful. PMID- 17338941 TI - Rapid identification of Fonsecaea by duplex polymerase chain reaction in isolates from patients with chromoblastomycosis. AB - Fonsecaea pedrosoi is the most common etiologic agent of chromoblastomycosis. F. pedrosoi and other dematiaceous fungi are usually identified by morphologic studies. We have developed a duplex polymerase chain reaction (PCR) targeting the ribosomal DNA for rapid and more specific identification of the genus Fonsecaea. DNA samples from 103 isolates of Fonsecaea species and other dematiaceous fungi were amplified by PCR using universal and specific primers targeting ITS1-5.8S ITS2 region of the ribosomal DNA. Universal primers were used for detection of non-Fonsecaea DNA. Fonsecaea-specific PCR product was found in 70 (68.0%) isolates including 4 strains that did not develop conidiogenesis. Thirty non Fonsecaea and 3 Fonsecaea compacta isolates were negative by duplex PCR. These results were confirmed by DNA sequencing analysis indicating the high specificity of the duplex PCR assay. In conclusion, the duplex PCR is a rapid and specific assay for identification of Fonsecaea isolates mainly for the strains that are difficult to identify by morphologic methods. PMID- 17338942 TI - Validation of the agar proportion and 2 liquid systems for testing the susceptibility of Mycobacterium tuberculosis to moxifloxacin. AB - Moxifloxacin (MOX), an 8-methoxyquinolone compound, is now widely used for the treatment of bacterial infections and also accepted as 2nd-line drug for the treatment of multidrug-resistant (MDR) tuberculosis. To tentatively correlate the clinical outcome with in vitro results, we sought to set up susceptibility test conditions for Mycobacterium tuberculosis against MOX by using the reference agar proportion method, the BACTEC 460 radiometric system, and the recently validated nonradiometric BACTEC MGIT 960 system. Our aim was to determine the critical MOX test concentration to be used with the abovementioned methods for routine susceptibility testing. MICs were determined for 20 pan-susceptible strains, 10 MDR strains, and 10 fluoroquinolone-resistant strains with defined gyrA mutations. MOX MICs resulted in a bimodal pattern with values for gyrA mutants considerably higher than those for pan-susceptible and MDR strains. Our data showed that a concentration of 0.5 microg/mL allowed a clear-cut separation between susceptible and resistant strains when tested by all the studied methods. Confirmatory test with a subset of pan-susceptible and MDR isolates appeared to validate the selected critical concentration. The MOX-resistant strains were almost isolated from patients with prior fluoroquinolone exposure. PMID- 17338944 TI - Immune responses to infection. AB - The inflammatory and immune response to infection is a complex physiologic process targeted at removing foreign invaders, or pathogens, from the body. The initial inflammation that occurs may eliminate the pathogen, so that no infection results. If the inflammatory response is insufficient to remove the pathogen from the body, the acquired immune system becomes activated, stimulating the actions of T and B lymphocytes, which also attempt to eradicate the infectious pathogen. If this activity is successful, the body remains free of infection. If the pathogen remains viable in the body despite inflammatory and immune system actions, active infection ensues. The severity of the infection and the body's response depend on a multitude of factors including intactness of barrier defenses, immune competence of the host, virulence of the invading organism, and other underlying disease processes at work in the body. The critical care nurse must understand the inflammatory and immune responses to infection to appreciate the local and systematic effects of infection in the body and the rationale for treatment modalities. PMID- 17338945 TI - An anatomy of an infection: overview of the infectious process. AB - The immune system remains an enigmatic system in that each discovery leads to more questions and speculation. It is essential for the critical care nurse to understand the basic physiology that occurs in infections to address the issues in patients in an efficient and timely manner. Thorough patient assessment helps determine predictors and priorities. Although the protective barrier of an intact integument system often is identified as the first and best line of defense against infections, this defense can be strengthened by a critical care nurse who is equipped with the knowledge and understanding of the immune system, the latest research, and the dynamics that ensue within the patient. PMID- 17338946 TI - Bacterial infections: management by acute and critical care nurses. AB - Acute and critical care nurses must maintain a current knowledge base for advancing science and providing direct care for patients. When an infectious process is involved, it is the practicing nurse who must be knowledgeable in treatment and prevention modalities. The integument is the body's first line of defense for invading bacteria. This barrier to bacteria is followed by inflammation and adaptive immunity, the second and third lines of defense against infectious bacteria. It is acute and critical care nurses, however, who should be the first line of defense in preventing the spread of infectious disease. Modern medicine and common sense interventions reviewed in this article are the patient's best defense to good health and wellness when used by nurses. PMID- 17338947 TI - Rickettsial and other tick-borne infections. AB - Tick bites are best prevented by people avoiding tick-infested areas. When this is not possible, tick bites may be prevented by the wearing of long trousers that are tucked into boots. The best method to avoid tick bites is twofold: application of a topical deet (N,N-diethyl-m-toluamide) repellent to exposed skin, and treatment of clothing with permethrin. This system is currently used by the US Army to protect soldiers. Ticks can crawl underneath clothing and bite untreated portions of the body; therefore, treating clothing is imperative. Permethrin is nontoxic to humans, and can be used in any age group. Permethrin is commercially available. Checking clothing regularly while in tick-infested areas is highly recommended to back up the few hours of protection provided by the insect repellents. It is also recommended that the entire body be carefully screened for ticks and other parasites by campers and hunters while they are staying in and after leaving infested areas. Any tick found should be removed immediately. Removing ticks may not be easy. It is best to use blunt, rounded forceps, and a magnifying glass to remove ticks, especially when immature ticks are found. The forceps are used to grasp the mouthparts of the tick as close as possible to the skin, and then the tick is pulled upward, perpendicular to the skin, with a continuous and steady action. Usually any mouth parts of the tick retained in the skin are eliminated uneventfully by the body. Other methods of removing ticks, such as using fingers, lighted cigarettes, petroleum jelly, or suntan oil, should be avoided. Killing the tick in situ may increase the risk of regurgitation by the tick and the transmission of infectious agents. Most stick bites are uncomplicated, and result only in benign cutaneous inflammatory reactions that may be pruritic for a few days. As a result of mouthparts being retained at the feeding site, a granuloma may rarely develop. There are no data to indicate that antimicrobial prophylaxsis is beneficial to the tick-bitten patient to prevent disease. It must be kept in mind that the risk of transmission of disease increases with the duration of attachment and generally requires greater than 24 to 48 hours. The degree of tick engorgement or the time since tick exposure and discovery of the tick may be used to establish the likely duration of attachment and the risk of disease transmission. Reducing and controlling tick populations is difficult. Habitat modifications, including vegetation management by cutting, burning, and herbicide treatment, and drainage of wet areas are one strategy for tick control, but their effects are often short lived, and they can cause severe ecologic damage. Chemicals used to control ticks may cause environmental contamination, and therefore, toxicity for humans and animals. Biologic control methods for ticks include the promotion of natural predators. Natural predators of ticks are beetles, spiders, and ants, and parasites such as insects, mites and nematodes. Tick control is best based on the concept of integrated pest management, in which different control methods are adapted to one area or against one tick species with due consideration to their environmental effects. Tick-borne diseases are increasing in prevalence. Perhaps it is because people are undertaking more outdoor activities, which result in contact with ticks and their pathogens. Clinicians should be aware of the clinical sign of tick-transmitted diseases, because morbidity and mortality as a result of these diseases increases substantially if there are delays in diagnosis and treatment. Tick-borne illness occur in distinctive geographic areas. The reporting of these illnesses and diseases to the health department enables the gathering of information and statistics. The public should be informed about the risks of disease in tick-infested areas and the means of preventing infections. The most common diseases are caused by Rickettsia, Borrelia, and Ehrichia, but with continued study, new pathogens and diseases will continue to emerge. PMID- 17338948 TI - Spirochete infections: Lyme disease and southern tick-associated rash illness. AB - This article describes the etiology, symptoms and stages, pathophysiology, diagnosis, treatment, and prevention of Lyme disease and a cluster of similar symptoms called "Southern tick-associated rash illness." It is important for the critical care nurse to be alert to the possibility of these infections because some of the symptoms can have devastating effects on the heart and meninges. In some cases Lyme disease may be a comorbidity, not the primary reason a patient is admitted to an ICU. The cause of the symptoms must be recognized for effective treatment to be initiated. PMID- 17338949 TI - Antimicrobials: classifications and uses in critical care. AB - Patients in the critical care setting are at high risk for infection because their normal host defenses are compromised. Critical care patients frequently have complicated, multisystem, mixed infections that can be life threatening. Optimal patient outcomes are the result of (1) early identification of signs and symptoms of infection; (2) nursing knowledge about common antimicrobials and their side effects and adverse reactions; (3) obtaining cultures before starting empiric therapy with antimicrobials; (4) consulting as needed with the infection control team; (5) practicing basic measures of infection control, such as hand washing; and (6) using special isolation precautions when the patient's condition warrants special care. The nurse also needs to be vigilant to the signs of toxicity from antimicrobial therapy. These interventions can save the critical care patient's life, prevent others from becoming infected, and save the hospital precious fiscal resources. PMID- 17338950 TI - Antimicrobial resistance in critical care. AB - Patients presenting with active infections or at increased risk for infections pose a significant challenge in critical care nursing. It is important for critical care nurses to use effective antimicrobial strategies in patient management to reduce the potential development of antimicrobial resistance. They should be involved actively in promoting patient management through development of research-based nursing guidelines and protocols. PMID- 17338951 TI - Methicillin-resistant Staphylococcus aureus in critical care areas. AB - In recent years the mainstay of treatment for hospital-associated MRSA infections has been vancomycin, but now vancomycin intermediate S aureus strains are beginning to emerge. Complete vancomycin resistant S aureus can develop, possessing the same vanA gene as vancomycin-resistant enterococcus. Four such isolates have been reported, three of which have been in the United States. There are new antibiotics being developed, but there is always a risk of resistance developing. There are some promising new ideas such as staphylococcal conjugate vaccines that reduce the rates of S aureus bacteremia for up to 10 months postimmunization in patients who have end stage renal disease receiving hemodialysis, but studies are ongoing. With all the uncertainty surrounding treatment, at least one medium has remained consistent and effective if used properly--infection control. But this requires complete support of all healthcare workers and hospital administration from the chief medical officer to doctors and nurses to environmental services personnel to take ownership of an effective infection control program. Who will advocate for more stringent infection control policies and for the equipment to successfully carry them out? Who will take the lead by ensuring implementation of infection control policies on a unit is effective? Who will hold themselves and other health care workers including physicians accountable to comply with these infection control policies every time they enter a patient's room? Nurses are on the front lines in the battle against antibiotic-resistant nosocomial infections such as MRSA, and we should not be apathetic or feel we are helpless. It is our duty as patient advocates not to take a spectator role but to answer these questions: "I will." PMID- 17338952 TI - Vancomycin-resistant enterococcus in critical care areas. AB - Colonization with VRE must be identified to prevent the spread of the disease and the progression to infection in susceptible individuals. PCR assays and culturing techniques allow nurses and other members of the health care team to identify and treat colonized and infected patients. Although currently there is no effective treatment for VRE colonization, isolation precautions are paramount to prevent increased VRE transmission. Decolonization techniques should be considered in high-risk populations. For those who have clinical evidence of VRE infection, several approved treatment regimens can be implemented. The increasing incidence of VRE with simultaneous increasing resistance patterns demands the development of new antimicrobial agents. Collaborative management of both VRE colonization and infection can reduce the sky-rocketing numbers of hospital acquired infections and mortality from VRE infections. PMID- 17338953 TI - Sepsis in critical care. AB - Sepsis is a syndrome produced by the accelerated activity of the inflammatory immune response, the clotting cascade, and endothelial damage. It is a systematic process that can progress easily into septic shock and MODS. The chemical mediators or cytokines produce a complex self-perpetuating process that impacts all body systems. It is critical for the nurse first to identify patients at risk for developing sepsis and to assess patients who have SIRS and sepsis continually for signs and symptoms of organ involvement and organ dysfunction. Once sepsis has been diagnosed, evidence-based practice indicates initiation of fluid resuscitation. Vasopressor therapy, positive inotropic support, and appropriate antibiotic therapy should be started within the first hour. Within a 6-hour timeframe the goal is stabilization of the CVP, MAP, and UOP to prevent further organ damage. The challenge for nurses caring for septic patients is to support the treatment goals, to prevent added complications including stress ulcers, DVTs, aspiration pneumonia, and the progression to MODS, and to address the patient's and the family's psychosocial needs. As complex as the pathophysiology of sepsis is, the nursing care is equally complex but also rewarding. Patients who previously might have died now recover as vigilant nursing care combines forces with new drug therapies and evidence-based practice guidelines. PMID- 17338954 TI - Making sense of multiple organ dysfunction syndrome. AB - Despite recent advances in critical care medicine, caring for patients with MODS remains one of the most challenging experience a critical care can encounter. New therapies that current exist and continue to be developed contribute to successful outcomes for patients with MODS, but there is no substitute for prevention and early intervention for persons at risk for developing MODS. Early and subtle changes in the patient who is at risk and has endured an initial insult can make a great difference in the patient's outcome and chances of mortality. Goal-directed therapy, supportive management, as well as an understanding of the inflammatory process are key to decreasing the mortality rate among patients with MODS. PMID- 17338955 TI - Managing the infected heart. AB - Most infective processes are straightforward and can be diagnosed from bacterial findings in a single test. IE does not always follow this tenet, so establishing the diagnosis can be difficult. The salient features of IE may present atypically or be obscured by the presence of preexisting and coexisting diseases. Flulike symptoms may mask the beginning of this devastating disease. Early diagnosis of IE is important because of its high risk of morbidity and mortality. Management of the patient who has IE is complex and requires interventions by infectious disease specialists, cardiologists, respiratory therapists, and critical care nurses to address the many multifaceted complications. Early evaluation, diagnostic validation, multidisciplinary management, prompt pharmaceutical initiation, and intense critical care nursing intervention are necessary to reduce the probability of long-standing complications and to improve patient outcomes. PMID- 17338957 TI - Letter from the president. PMID- 17338956 TI - Avian influenza: are we ready? AB - We cannot be certain when the next influenza pandemic will emerge, or even whether it will be caused by avian influenza (H5N1) or some unrelated virus. However, we can be certain that an influenza pandemic will occur. The United States is leading the scientific effort to contain the pandemic through vaccine studies and antiviral studies. The need for pandemic influenza preparedness is extensive and expensive. Planning entails increased development of antivirals and vaccines, effective surveillance systems not only for people, but in agriculture, effective communication systems, plans to continue essential services, identification of health care priorities, and thorough guidelines for care. Critical care nurses, as well as all health care professionals, need to consider where their personal and professional obligations meet and end. There should already be discussions of contingency plan of the institution in which they are employed and the community in which they live. Additionally, a personal plan for their families with regard to economics, safety, and optimizing personal health outcomes during such a crisis should be considered. As many have said, "It is not a matter of if, but rather of when." Although the pandemic might not be the avian flu, history has taught us that pandemics surface with little warning and can have devastating effects on human lives, and can over tax the already fragile health care system. PMID- 17338958 TI - Castleman's disease: A rare lymphoproliferative disorder. AB - Castleman's disease (CD) is an atypical lymphoproliferative disorder. Since it was first described in 1956, it has been referred to as follicular lympho reticuloma, angiofollicular mediastinal lymph node hyperplasia, and benign giant lymphoma. CD is a heterogeneous disease that can be either localized or systemic (multicentric). The localized form can be divided into two types: the hyaline vascular (HV) type or the plasma cell (PC) type. The former usually produces few symptoms and histological features include abnormal follicles and increased interfollicular vascularity. The PC type, in which, histopathologically, the presence of sheets of mature plasma cells is the distinguishing feature, is more likely to produce clinical symptoms such as fever, night sweats, and lymphadenopathy. The multicentric form mimics the PC type of localized CD, and patients present with systemic symptoms. In this report, we discuss the spectrum of clinical and pathological findings in localized and multicentric CD. PMID- 17338959 TI - The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. AB - Rhabdomyolysis is defined as a pathological condition of skeletal muscle cell damage leading to the release of toxic intracellular material into the blood circulation. Its major causes include trauma, ischemia, drugs, toxins, metabolic disorders, and infections. The pathophysiological hallmark of the syndrome is an increase in intracellular free ionized calcium due to either cellular energy depletion, or direct plasma membrane rupture. The increased intracellular calcium activates several proteases, intensifies skeletal muscle cell contractility, induces mitochondrial dysfunction, and increases the production of reactive oxygen species, ultimately resulting in skeletal muscle cell death. Clinically, the syndrome presents with severe muscular pain, weakness and myoglobinuria. Increased myoglobin and creatine phosphokinase as a consequence of muscular cell death are the major laboratory findings, which, in combination with the clinical presentation, lead the clinician to the final diagnosis of the syndrome. PMID- 17338960 TI - A new direction for medical education in Ireland? AB - In recent years, new concepts of educational theory and practice have stimulated new approaches to medical education in many countries. For various reasons, medical education in Ireland has been slow to change such that there are now increasing concerns about educational standards. In addition, Ireland currently produces too few doctors and is therefore highly dependent on overseas doctors to maintain its health service. The responsible agencies are finally about to address these problems through a major expansion of medical education coupled with a strong agenda for educational reform. While the reform process will clearly be influenced by the experience of other counties, Ireland now has a great opportunity to take innovation in medical education a step further. For example, there is now an opportunity to develop new strategies to ensure the social accountability of medical education, to increase its community orientation and to foster interprofessional teaching and learning. PMID- 17338961 TI - Core competencies of the European internist: A discussion paper. AB - In an attempt to enhance the quality of internal medicine practice and to reform the education of internists across Europe, the European Board of Internal Medicine (formed by the European Federation of Internal Medicine and the European Union of Medical Specialists Section of Internal Medicine) has launched a project aimed at defining core competencies that are common to all internists. The compilation of six core competencies presented in this paper consists of patient care; medical knowledge; communication skills; professionalism, ethical, and legal issues; organizational planning and service management skills; and academic activities. These core competencies are the foundation required for the provision of high-quality medical care everywhere, regardless of the professional traditions and organization of health care in different countries. The authors hope this paper will stimulate constructive discussion and thoughtful debate, and that it will be followed by a collaborative effort to develop and endorse a European consensus. PMID- 17338962 TI - Acute phase proteins in patients with acute coronary syndrome: Correlations with diagnosis, clinical features, and angiographic findings. AB - BACKGROUND: C-reactive protein (CRP) plasma levels increase in patients with acute coronary syndrome (ACS). The role and implications of increased plasma concentrations of other acute phase proteins (APPs), such as alpha-1-antitrypsin (A1AT), alpha-1 glycoprotein (A1GP), haptoglobin (HG), ceruloplasmin (CP), and C3c and C4 complement fraction, in patients with ACS are still not completely defined. METHODS: A total of 218 consecutive patients with ACS were included in the study, 185 with acute myocardial infarction (AMI) and 33 with unstable angina (UA). In all patients, A1AT, A1GP, HG, CP, C3c and C4 complement fraction, and CRP were evaluated within 12 h after the onset of symptoms. Sixty-two patients with AMI underwent coronary angiography. RESULTS: APPs showed a significant correlation with CRP concentrations. Patients with AMI had higher concentrations of A1AT and HG than UA patients. Cholesterol levels were correlated with APPs in patients with AMI. Patients with three coronary vessel disease or LAD disease had significantly higher C3c concentrations. Coronary collateral flow was associated with higher A1GP and CP concentrations, and total coronary occlusion with A1AT and CP. CONCLUSIONS: APPs were correlated with CRP concentrations in subjects with ACS. The increase in APPs in patients with ACS seems to be linked to the entity of myocardial damage and coronary atherosclerotic burden. PMID- 17338963 TI - A comparative study of an ambulatory blood pressure measuring device and a wrist blood pressure monitor with a position sensor versus a mercury sphygmomanometer. AB - BACKGROUND: Self-measurements of blood pressure (BP) and 24-hour BP measurements are better predictors of cardiovascular mortality and morbidity than office BP measurements. The objective of this study was to compare the accuracy and precision of a wrist BP monitor with a position sensor (Omron 637IT) and of an ambulatory BP measuring monitor (ABPM; Nissei DS-250) with a mercury sphygmomanometer. METHODS: A total of 139 patients (69 women and 70 men) were included in the study. The BP of each subject was first measured with a mercury device using the same (left) arm. After this, the wrist monitor was used for BP measurement. Upon completion of the BP readings, 24-hour BP monitoring was performed using Nissei DS-250 monitors. Mean and standard deviations were calculated for all devices. In order to assess the agreement between the measurement methods, the Bland-Altman method and graphics were utilized. RESULTS: The mean systolic BP measured by the mercury device was 133.2+/-18.4 mmHg and the diastolic BP was 85.4+/-12.5 mmHg, whereas the digital device measured systolic BP as 135.7+/-17.2 mmHg and diastolic BP as 87.0+/-12.5 mmHg. The 24-hour BP measurement was 134.6+/-16.6 mmHg for systolic BP and 85.6+/-11.1 mmHg for diastolic BP. The difference with regard to systolic BP between the mercury and the Omron devices was -2.5+/-5.3 mmHg, which is within the AAMI standard. However, while the mean values of the differences between the mercury and ABPM devices remained under 5 mmHg, their standard deviation was above +/- 8 mmHg. For diastolic BP, the difference between all of the devices was below 5+/-8 mmHg. CONCLUSIONS: The wrist BP monitor produced results consistent with those of the mercury sphygmomanometer when both were compared with the results of the ABPM. As BP measurement with these devices is a practical and repeatable method, they can be used instead of ABPM in the diagnosis and monitoring of hypertension. However, there is a need for further comparative studies. PMID- 17338964 TI - Dynamics of serum C-reactive protein (CRP) level and cosmophysical activity. AB - BACKGROUND: C-reactive protein (CRP), an acute phase reactant, plays an important part in the investigation of the role of inflammation in pathology. Many cardiovascular events show significant associations with various cosmophysical parameters. The aim of this study was to investigate the relationship between the level of CRP and the levels of solar, geomagnetic (GMA), and cosmic ray activity. METHODS: The results of 25,399 serum CRP tests carried out over a 3-year period were compared with the monthly and daily levels of solar, geomagnetic, and cosmic ray activity during the same period. The cosmophysical data were obtained from the National Oceanic Atmospheric Administration (NOAA) in the U.S. and from the Russian Academy of Science. RESULTS: On a monthly basis, CRP levels showed no correlation with GMA (n=36, r=0.258, p=0.13), but there was a significant inverse relationship with neutron activity (r=-0.35, p=0.03). For the daily comparisons, CRP levels were significantly correlated with GMA (n=1057, r=0.97, p=0.02), and there was a significant inverse relationship with neutron activity (r=-0.97, p=0.025). Daily neutron activity was higher on days with CRP levels of 0-1.0 mg/dl (n=289) and above1.0-1.5 mg/dl (n=1213) than on days with higher CRP values (>1.5; n=23,897; p<0.0001). CONCLUSION: The level of serum CRP, in addition to its association with inflammation, is related to the daily level of GMA and inversely to the level of neutron activity. PMID- 17338965 TI - Propeptide of procollagen type I (PIP) and outcomes in decompensated heart failure. AB - BACKGROUND: Changes in extracellular matrix are recognized as a contributing factor in the cardiac remodeling process. Several studies have addressed the value of turnover markers of collagen as predictors of death or new heart failure episodes. The aim of the present study was to evaluate the relationship between peripheral serum concentration of propeptide of procollagen type I (PIP) and outcomes in patients with decompensated heart failure. METHODS: A total of 111 patients admitted to our Unit between September 2000 and May 2003 for decompensated heart failure were analyzed. Death from any cause or due to heart failure and readmission were considered primary endpoints. RESULTS: The mean PIP concentration was 80.84+/-36.40 ng/mL. The PIP serum level was significantly higher among those patients who suffered some endpoint during follow-up (88.12+/ 37.31 ng/mL vs 73.13+/-34.06 ng/mL; p=0.029). Twenty-five (22.52%) of the 111 patients died during the 21 months of follow-up, and 54 (48.6%) were readmitted with new bouts of heart failure. Using Cox proportional hazards regression analyses, serum PIP levels, systolic dysfunction, and diabetes mellitus were identified as independent predictors of death. Serum PIP levels, age, and sex were independent predictors of new heart failure episodes and readmission. CONCLUSION: A single serum measurement of PIP seems to have prognostic value in patients with decompensated heart failure. Accordingly, patients with higher values of PIP at decompensation are at a higher risk of death or readmission during follow-up. PMID- 17338966 TI - Evaluation of exercise testing for subjects with isolated proteinuria and/or hematuria of unclear significance. AB - BACKGROUND: A frequent problem that family doctors face is the meaning of small quantities of blood or protein in urine samples. Patients with this problem are often either neglected or referred to specialists for complex, expensive, and often invasive diagnostic procedures. Exercise testing has never been considered in nephrology, except for some attempts in diabetic patients. METHODS: We report on a study conducted over 12 years with patients referred for slight hematuria and/or proteinuria to determine whether exercise testing could be a diagnostic aid in some or all of them. We performed exercise testing using a treadmill preceded and followed by urine analysis, with a kidney biopsy within 10 days. Of the 94 patients enrolled in the study, only those with a positive exercise test turned out to have parenchymal nephropathy. At the end of the study, we simplified the quantification of exertion, dispensing with the treadmill and drastically reducing the number of urinary parameters considered. RESULTS: In patients with histological evidence of kidney damage, most of the variables increased significantly after the test. Statistical analysis also showed that determination of proteinuria and hematuria alone guaranteed maximum predictability. We found that it is also possible to simplify the quantification of effort/exertion and to drastically reduce the number of urinary parameters and still obtain significant results. CONCLUSIONS: Exercise testing provides useful information about the significance of microhematuria and proteinuria, reducing the number of cases that need to be referred to specialists. The method needs to be validated in other studies, but our results suggest that family doctors could use simple dipsticks to screen the many cases of microhematuria or proteinuria observed in daily practice. The method seems useful in eliminating doubts and unnecessary diagnostic costs. PMID- 17338967 TI - Protean manifestations of pleural empyema caused by Streptococcus pneumoniae in adults. AB - BACKGROUND: The aim of this study was to describe the clinical characteristics of pleural empyema caused by Streptococcus pneumoniae. METHODS: A retrospective cohort analysis was conducted at the University Hospital 12 de Octubre, Madrid (Spain). We included all adult patients with pleural empyema caused by S. pneumoniae diagnosed from 1998 to 2004. RESULTS: Eighteen cases of pleural empyema due to S. pneumoniae were analyzed. Fourteen patients had symptoms of respiratory infection, three had other symptoms, and one patient was asymptomatic. One-third of the patients did not have a pneumonia infiltrate visible on chest radiogram. In 46%, bacteremia was detected. All pleural fluids had a high white blood cell count, either with polymorphonuclear or lymphocytic predominance. Drainage with a chest tube was used in 94.4% of cases. Nine patients had a favorable outcome, five had to be admitted to the intensive care unit, and two died within the first week (mortality rate of 11.1%). CONCLUSIONS: Pleural empyema caused by S. pneumoniae has to be considered an aggressive disease that, occasionally, affects young and previously healthy individuals. Clinical manifestations are variable and pleural fluid can be a lymphocytic exudate. It has a noticeable associated morbidity and mortality, which must be kept in mind by clinicians when approaching a patient with a pleural effusion. PMID- 17338968 TI - Fever revealing Behcet's disease: Two new cases. AB - Behcet's disease (BD) is an uncommon cause of fever of unknown origin. We report two cases, both involving 42-year-old males, who initially presented with prolonged fever and who were ultimately diagnosed as having BD after a delay of 12 and 21 months, respectively. Both patients developed pulmonary aneurysms. Although fevers resolved after therapy, both patients died within the first year after diagnosis. Clinicians should be aware that long-term fever may be an inaugural sign of BD, especially in individuals living in countries along the ancient Silk Road or Mediterranean basin. PMID- 17338969 TI - Wegener's granulomatosis overlapping with Takayasu's arteritis revealed by FDG PET scan. AB - We report the case of a 23-year-old woman who initially presented with Wegener's granulomatosis (WG) limited to the lungs, diagnosed on the basis of a biopsy of an upper left lobe nodule and elevated ANCA titers. Remission occurred under treatment with methylprednisolone and intravenous immunoglobulins. Later in the course of the disease, findings highly suggestive of Takayasu's arteritis (TA) appeared: murmur at the level of the left subclavian artery, thickening of the arterial wall of the aorta and pulmonary arteries on tomodensidometry, and abnormal uptake of the aortic arch and ascending aorta on FDG-PET scan. This latter exam also showed an increased uptake of an already known pulmonary nodule, due to WG. Although five cases of WG occurring together with TA have previously been reported, this is the only one in which TA was revealed by FDG-PET scan. In the specific setting of overlapping vasculitides, FDG-PET scan may be helpful in simultaneously evaluating the activity of the two diseases. PMID- 17338970 TI - Typhoid fever in travelers: Time for reassessment. AB - Enteric fever (EF) is the most common bacteremic disease affecting travelers to the tropics. For more than a decade, fluoroquinolones have been considered the drugs of choice for EF. However, recent reports have raised concern about fluoroquinolone resistance. Treatment with ciprofloxacin failed in a traveler with Salmonella paratyphi EF who had recently returned from India. Treatment failed despite minimum inhibitory concentrations of fluoroquinolones within the susceptible range. Further in vitro investigations revealed very low serum bactericidal activity with ciprofloxacin. Clinicians should be aware of the recent changes in the interpretation of Salmonellae sensitivity. PMID- 17338971 TI - The challenges of extrapulmonary presentations of sarcoidosis: A case report and review of diagnostic strategies. AB - A patient presenting with overweight, amenorrhea, diabetes insipidus, and oral, nasal, and pharyngeal inflammation was admitted to our hospital. Using a non invasive approach, we were able to narrow the differential diagnosis down to a systemic lymphoproliferative or granulomatous disease, most likely sarcoidosis. This diagnosis was eventually confirmed by a biopsy of an enlarged tonsil. To our knowledge, tonsil biopsies have not been reported to be of help in the diagnostic strategy for systemic sarcoidosis. In this report, we review the possible diagnostic approaches and point out that the pharyngeal tonsils, if enlarged or inflamed, can be targeted to obtain tissue for histological confirmation. PMID- 17338972 TI - Adult Still's disease despite the presence of positive antinuclear antibodies. AB - We report the case of a 60-year-old woman who had recently been examined for fever of unknown origin and who presented to our hospital with high fever and myalgia, weakness, sore throat, and rash. The patient had a markedly elevated serum ferritin concentration of 40,000 ng/mL and positive antinuclear antibodies (ANA) with a titer of 1/200. Despite the presence of positive ANA, the patient was diagnosed as having adult Still's disease (ASD). High-dose steroid therapy resulted in a remarkable clinical improvement. Such a severe case of systemic inflammatory response syndrome, masquerading as sepsis with a positive ANA test, has not been reported previously, at least not in the last 15 years. PMID- 17338973 TI - A rare presentation of visceral leishmaniasis without fever or splenomegaly in an elderly person. AB - Visceral leishmaniasis (kala azar) is characterized by fever and splenomegaly in more than 80% of cases. We report a case of kala azar in an elderly person with severe anemia but no other typical features. This highlights the importance of being aware of rare presentations to avoid missing the diagnosis of this potentially fatal, but fully treatable, condition. PMID- 17338974 TI - Endotracheal metastases in renal cell carcinoma: A life-threatening but treatable complication. AB - Endotracheal obstruction, by primary bronchogenic carcinoma or by metastases from extrapulmonary tumors, is a rare and life-threatening complication in cancer patients. The trachea is an extremely rare location for metastases from non pulmonary tumors. We report a patient with metastatic renal cell carcinoma who developed almost complete obstruction of the trachea and who was successfully managed with bronchoscopic resection of endotracheal metastases. PMID- 17338975 TI - Pulmonary Nocardia nova infection. PMID- 17338976 TI - Severe rhabdomyolysis secondary to simvastatin and acenocoumarol. PMID- 17338977 TI - Acute myocardial infarction during intravenous immunoglobulin (IVIG) therapy. PMID- 17338978 TI - The role of the internet in facilitating yellow oleander poisoning and in providing effective treatment. PMID- 17338979 TI - "Antibodies in cancer treatment". PMID- 17338980 TI - Expanding our perspective. PMID- 17338981 TI - Negative life events: risk to health-related quality of life in children and youth with HIV infection. AB - Children and youth with perinatally acquired HIV infection are living longer because of improved drug therapies, but they may be at risk for poor health related quality of life (HRQOL) outcomes because of nondisease factors. Families affected by HIV disease are more likely to experience major negative life events (NLEs). The effects of NLEs, shown to impact HRQOL in children with other chronic illnesses, have not been evaluated in children with HIV infection. The primary objective of this study was to determine if NLEs occurring in the previous 12 months were associated with increased risk for poorer outcomes in three measures of HRQOL (health perception, behavior problems, and symptom distress) in a cohort of children and youth with HIV infection. The authors conducted a cross-sectional analysis of data determined in 1999 from 1,018 children and youth 5 to 21 years of age enrolled in a longitudinal follow-up study. Multivariate logistic regressions estimated the odds for worse HRQOL outcomes. Children and youth with one or more NLEs had significantly lower health perceptions, more behavior problems, and greater symptom distress than children with no reported NLEs. The occurrence of NLEs may present a significant nondisease risk for diminished HRQOL among children and youth challenged by HIV disease. Nursing efforts to support these younger patients and their families sustaining major family disruption caused by NLEs may improve overall health outcomes in this vulnerable population. PMID- 17338982 TI - Hearing consumer voices: planning HIV/sexually transmitted infection prevention in alcohol detoxification. AB - The literature has provided ample evidence that individuals abusing or dependent upon alcohol are at high risk for contracting HIV and other sexually transmitted infections (STIs). Despite the documented need of this vulnerable group for targeted HIV/STI prevention efforts, no prior research has explored the efficacy and feasibility of HIV/STI prevention for individuals in alcohol detoxification. The current study sought the voices of consumers of such services to get their guidance about successful and necessary features of HIV/STI prevention programs targeted to their needs. Two focus groups conducted yielded exceptionally helpful information. Consumers clearly want to be educated about HIV/STI, seeing this as crucial to their physical well-being and safety. They voiced preferences for nonjudgmental counselors who meet with them on an individual basis in contexts that protect consumer privacy. A clear set of guidelines emerged for an intervention structure that, if carefully honored, has strong likelihood of success in protecting individuals in alcohol detoxification from HIV/STI. PMID- 17338983 TI - Human avian influenza: how ready are we? AB - Three influenza pandemics emerged in the 20th century, and scientists are concerned that the currently circulating, highly pathogenic A (H5N1) avian influenza virus could lead to the next pandemic, one as deadly as the 1918 influenza pandemic. Not since the identification of HIV and AIDS will the duty to care among health care providers be tested as during such an event. Nonetheless, the expertise of health care providers is an integral part of the response to a pandemic. In the fight against flu, forewarned is forearmed. This report provides an overview of avian influenza (a.k.a. bird flu) and phases of pandemic influenza, with an emphasis on what health care providers should know to be prepared for a human avian influenza outbreak and the next pandemic. PMID- 17338984 TI - Ritonavir-boosted protease inhibitors: impact of ritonavir on toxicities in treatment-experienced patients. AB - The purpose of this review is to discuss the basis for ritonavir boosting of protease inhibitors as well as the complications and benefits associated with ritonavir boosting when designing an antiretroviral regimen for treatment experienced patients. Such patients have fewer viable options because of cross resistance arising from previous regimen failures. Ritonavir administered at a low dose to boost another protease inhibitor may be a useful strategy for achieving virological efficacy while minimizing the toxicities associated with full-dose ritonavir. There may be an increased risk of adverse events associated with increased plasma concentration of the concurrent protease inhibitor. Still, the incidence of these adverse events is generally low, and clinical trials have suggested that they rarely result in discontinuation or alteration of the regimen. In highly treatment-experienced patients in particular, the potential benefits associated with ritonavir boosting usually outweigh the risks. PMID- 17338985 TI - Knowledge and attitudes of mariners about AIDS in Turkey. AB - Given the significant high risks of both being exposed to the virus and spreading it, mariners traveling across countries on a regular basis fall into one of the top-priority populations of those to whom education on HIV/AIDS should be given. However, there have been no reports regarding HIV/AIDS knowledge and attitudes on the part of mariners in Turkey. Therefore, this study was carried out with the aim of defining the knowledge and attitudes of 660 Turkish mariners. Data were determined using a self-completed questionnaire. Percentage and mean scores were used in data analysis. Results show that the mariners' knowledge was inadequate (mean score was 52.31 +/- 20.46 over a total of 100 points). The lowest knowledge pertained to HIV/AIDS prevention (mean score was 44.62 +/- 19.97). About half of the mariners considered themselves to be in the risk group. Very few of them (10%) have had an AIDS test. Most (68%) were informed about HIV/AIDS by the media. These results show that the mariners need to increase HIV/AIDS knowledge about prevention, transmission, treatment information, motivation, and behavioral skills to decrease HIV/AIDS risky behaviors. The mariners had the least knowledge about HIV/AIDS protection. Having a critical role in preventing the transmission and spreading of diseases, nurses should conduct more extensive and advanced research into HIV/AIDS and assume educational and counseling responsibilities in illuminating society. PMID- 17338986 TI - Of provider shortages and immodest proposals. PMID- 17338987 TI - Reports from the XVI International AIDS Conference. PMID- 17338988 TI - Time to deliver: past due. PMID- 17338989 TI - Gender equity for the 21st century: the imperative for women to control their bodies. PMID- 17338990 TI - News in HIV prevention: microbicides. PMID- 17338991 TI - Reducing the spread of HIV and male circumcision. PMID- 17338992 TI - The orphan gap. PMID- 17338993 TI - A look at tuberculosis and its relationship to HIV/AIDS. PMID- 17338994 TI - New antiretroviral agents under development: a review from the XVI International AIDS Conference. PMID- 17338995 TI - XVI International AIDS Meetings: reflections on health and human rights. PMID- 17338996 TI - Double-blind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, pro-inflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure. AB - BACKGROUND: Statins decrease mortality in patients with coronary artery disease. However, chronic heart failure (CHF) patients were often excluded in such trials. Statins possess pharmacologic properties (independent of cholesterol lowering) that may be beneficial on ventricular remodeling in such patients. METHODS AND RESULTS: We conducted a 6-month randomized placebo (PBO)-controlled study of rosuvastatin (ROS) in patients with systolic (left ventricular ejection fraction [LVEF] <40%) CHF of ischemic or nonischemic etiology. The primary end point was change in LVEF by radionuclide ventriculogram. Secondary end points included change in echocardiographic parameters, neurohormonal and inflammatory markers, Packer composite score, death, and heart failure hospitalization. Patients were well matched for baseline values. Compared with PBO (n = 46), ROS patients (n = 40) had a decrease in low-density lipoprotein cholesterol (PBO +3, ROS -54%, P < .001). There was no significant change in LVEF by radionuclide ventriculogram (PBO +5.3, ROS +3.2%), fractional shortening by echocardiographic (PBO +2.7, ROS +1.8%), left ventricular end-diastolic diameter (PBO -1.7, ROS +0.8 mm), left ventricular end-systolic diameter (PBO -1.9, ROS +0.1 mm). Plasma norepinephrine, endothelin-1, brain natriuretic peptide, hsCRP, tumor necrosis factor-alpha and interleukin-6, patient global assessment, Packer composite, death/heart failure hospitalization, and adverse events were similar between PBO and ROS. CONCLUSIONS: Despite being safe and effective at decreasing plasma cholesterol, high-dose ROS did not beneficially alter parameters of LV remodeling. Reasons for absence of benefit are uncertain, but may include patient population studied, high dose of ROS used or high use of effective background CHF medications. PMID- 17338997 TI - Prediction of rehospitalization and death in severe heart failure by physicians and nurses of the ESCAPE trial. AB - BACKGROUND: The predictive accuracy of physician investigators and nurse coordinators in estimating the risk of rehospitalization and death was determined for 373 hospitalized patients with severe advanced heart failure enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial. METHODS AND RESULTS: Estimates were made at discharge, and patients were followed for 6 months after hospitalization. A statistical prognostic model was developed from clinical and laboratory data for the end points of rehospitalization and death. Both nurse and physician predictions of death were generally associated with the observed deaths (c-indices of 0.675 and 0.611), although the nurses' prediction was significantly better (chi-square = 4.75, P = .029). The prediction ability of the prognostic model was similar to the physicians' model (c-index = 0.603). The predictions of rehospitalization were much weaker for nurse, physician and prognostic models. CONCLUSIONS: Nurses' estimations of survival in discharged, advanced-stage heart failure patients were superior to either physicians' or model-based predictions. Not nurses, physicians, or the prognostic model provided useful predictions for rehospitalizations, but this may have resulted from the fact that the rehospitalization estimates did not include the death risk. PMID- 17338998 TI - Rationale and design of the IRON-HF study: a randomized trial to assess the effects of iron supplementation in heart failure patients with anemia. AB - BACKGROUND: Anemia is a common finding in heart failure (HF) patients and has been associated with increased morbidity and mortality. It is generally denominated as anemia of chronic disease (ACD), but the association with true ferropenic anemia is common. Many studies have investigated the effects of treating anemia in HF patients with either erythropoietin alone or combination of erythropoietin and intravenous iron. However, the effect of iron supplementation alone in HF patients with ACD, ferropenic anemia, or both is unknown. METHODS AND RESULTS: IRON-HF study is a multicenter, investigator initiated, randomized, double-blind, placebo controlled trial that will enroll anemic HF patients with relatively preserved renal function, low transferrin saturation, low iron levels, and low to moderately elevated ferritin levels. Interventions are iron sucrose intravenously 200 mg once per week for 5 weeks, ferrous sulfate 200 mg by mouth 3 times per day for 8 weeks, or placebo. The primary objective is to assess the impact of iron supplementation (intravenously or by mouth) compared with placebo in HF patients with anemia from deficient iron availability. The primary end point is variation of peak oxygen consumption assessed by ergospirometry over 3 month follow-up. Secondary end points include functional class, brain natriuretic peptide levels, quality of life scores, left ventricular ejection fraction, adverse events, HF hospitalization, and death. CONCLUSIONS: The results of IRON HF should help to clarify the potential clinical impact of mild to moderate anemia correction in HF patients. PMID- 17338999 TI - Diagnostic characteristics of combining phonocardiographic third heart sound and systolic time intervals for the prediction of left ventricular dysfunction. AB - BACKGROUND: The third heart sound (S3) and systolic time intervals (STIs) are validated clinical indicators of left ventricular (LV) dysfunction. We investigated the test characteristics of a combined score summarizing S3 and STI results for predicting LV dysfunction. METHODS AND RESULTS: A total of 81 adults underwent computerized phonelectrocardiography for S3 and STI (Audicor, Inovise Medical Inc), cardiac catheterization for LV end-diastolic pressure (LVEDP), echocardiography for LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) testing. LV dysfunction was defined as both an LVEDP >15 mm Hg and LVEF <50%. The STI measured was the electromechanical activation time (EMAT) divided by LV systolic time (LVST). Z-scores for the S3 confidence score and EMAT/LVST were summed to generate the LV dysfunction index. The LV dysfunction index had a correlation coefficient of 0.38 for LVEDP (P = .0003), -0.53 for LVEF (P < .0001), and 0.35 for BNP (P = .0008). This index had a receiver operative curve c statistic of 0.89 for diagnosis of LV dysfunction; a cutoff >1.87 yielded 72% sensitivity, 92% specificity, 9.0 positive likelihood ratio, and 88% accuracy. CONCLUSIONS: In this preliminary study, the LV dysfunction index combined S3 and STI data from noninvasive electrophonocardiography, and yielded superior test characteristics compared to the individual tests for the diagnosis of LV dysfunction. PMID- 17339000 TI - Increased body temperature after reperfused acute myocardial infarction is associated with adverse left ventricular remodeling. AB - BACKGROUND: Fever is frequently observed in patients with acute myocardial infarction (AMI); however, its prognostic significance remains to be determined. We sought to determine the prognostic significance of increased body temperature (BT) after AMI. METHODS AND RESULTS: We examined 156 consecutive patients with reperfused first anterior AMI. Axillary BT was serially measured every 6 hours for a week. Patients were divided into quartiles by peak BT from the lowest to highest levels. Peak BT within the first week showed a significant positive correlation with peak C-reactive protein level (P < .0001), but not with peak creatine kinase level. There were positive correlations of peak BT with the incidence of pump failure (P = .022), left ventricular (LV) aneurysm (P = .029), and readmission for heart failure (P = .006). Higher peak BT was associated with greater LV end-diastolic volume (P = .031), greater end-systolic volume (P = .008), and lower LV ejection fraction (P = .014) 2 weeks after AMI. Multiple logistic regression analyses revealed that peak BT quartile was an independent predictor of in-hospital cardiac events (odds ratio = 1.61/quartile, P = .008). Furthermore, peak BT quartile was a significant predictor of readmission for heart failure by Cox proportional hazard model analysis (P = .048). CONCLUSIONS: Increased BT after AMI was associated with a worse clinical outcome and infarct expansion, suggesting a relationship between systemic inflammatory response and LV remodeling. PMID- 17339001 TI - Cardiac sympathetic denervation and ongoing myocardial damage for prognosis in early stages of heart failure. AB - BACKGROUND: Iodine-123-metaiodobenzylguanidine ((123)I-MIBG) can assess cardiac sympathetic nervous function. Heart-type fatty acid binding protein (H-FABP) has been used as a marker of ongoing myocardial damage. The prognostic value of combination (123)I-MIBG imaging and H-FABP in heart failure is unknown. METHODS AND RESULTS: We prospectively enrolled consecutive 104 patients with heart failure in whom we quantified (123)I-MIBG scintigraphy, simultaneously measured serum H-FABP and plasma brain natriuretic peptide (BNP) levels, and analyzed clinical outcomes. The multivariate Cox regression analysis revealed that augmented H-FABP level and decreased heart to mediastinum ratio of (123)I-MIBG at 240 minutes (delayed H/M ratio), but not BNP, were the independent predictors for cardiac events. The cutoff values for H-FABP and delayed H/M ratio were determined from the receiver operating characteristic curves as 5.2 ng/mL for H FABP and 1.73 for delayed H/M ratio. The cardiac event rate was markedly higher in patients with both H-FABP and delayed H/M ratio of (123)I-MIBG was abnormal. Conversely, no cardiac events occurred in patients with both H-FABP level and delayed H/M ratio were normal. CONCLUSION: H-FABP adds independent prognostic information to delayed H/M ratio of (123)I-MIBG imaging, and the combination of these approaches may improve the accuracy of prognostic determination in heart failure. PMID- 17339002 TI - Comparative evaluation of B-type natriuretic peptide, mid-regional pro-A-type natriuretic peptide, mid-regional pro-adrenomedullin, and Copeptin to predict 1 year mortality in patients with acute destabilized heart failure. AB - BACKGROUND: The aim of the present study was to evaluate the capability B-type natriuretic peptide (BNP) as a prognostic marker in patients with acute destabilized heart failure in comparison with mid-regional pro-A-type natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), and the C terminal part of the arginine vasopressin prohormone (Copeptin). METHODS AND RESULTS: BNP, MR-proANP, MR-proADM, and Copeptin plasma concentrations were obtained in 137 patients with acute destabilized heart failure attending a tertiary care hospital. The end point was defined as all-cause mortality, and the study participants were followed for 365 days. Of the 137 patients enrolled, 41 died and 96 survived during follow-up. ROC curve analysis showed that the areas under curve for the prediction of 1-year mortality were similar for BNP (0.716; 95% CI 0.633-0.790), MR-proANP (0.725; 95% CI 0.642-0.798), MR-proADM (0.708; 95% CI 0.624-0.782), and Copeptin (0.688; 95% CI 0.603-0.764). Using tercile approaches, Kaplan-Meier curve analyses demonstrated that the predictive value of all four analytes for survival probability was comparable (log-rank test for trend, P < .001 for each). In multivariable Cox proportional-hazards regression analyses, increased BNP, MR-proANP, MR-proADM, and Copeptin plasma concentrations were the strongest predictors of mortality. CONCLUSION: BNP is considered an established prognostic marker for heart failure patients. The present study provides evidence that MR-proANP, MR-proADM, and Copeptin measurements might have similar predictive properties compared with BNP determinations for one-year all cause mortality in acute destabilized heart failure. PMID- 17339003 TI - The biologic variability of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide in stable heart failure patients. AB - BACKGROUND: There are conflicting data on the usefulness of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the optimization of therapy for heart failure (HF). Discordant results may be explained by the intra individual variability of these peptides. This study evaluates the intraindividual variability of BNP and NT-proBNP and the impact of the covariates of age, sex, and renal function. METHODS AND RESULTS: Stable HF patients attending our unit were included. Blood samples were drawn 1 hour apart on 2 occasions 1 week apart. Forty-five patients were enrolled (69.6 +/- 12.1 years, 64% male, 84% systolic HF). Within-hour and within-week intraindividual variability were: 6.9% and 21.1% for NT-proBNP; 14.6% and 28.4% for BNP (P < .01 for within-hour comparison of BNP and NT-proBNP). Reference change values over 1 week for NT-proBNP and BNP were 49.2% and 66.2%, respectively. There were no significant relationships identified between variability and age, gender, or glomerular filtration rate. CONCLUSION: There is considerable intraindividual variability in these peptides in stable HF patients. Changes of approximately 50% and 66% for NT-proBNP and BNP from week to week are needed to indicate an altered clinical status and caution should be exercised in interpreting serial changes in these peptide levels when monitoring patient responses to treatment or clinical status. PMID- 17339004 TI - Telemonitoring for patients with chronic heart failure: a systematic review. AB - BACKGROUND: Telemonitoring, the use of communication technology to remotely monitor health status, is an appealing strategy for improving disease management. METHODS AND RESULTS: We searched Medline databases, bibliographies, and spoke with experts to review the evidence on telemonitoring in heart failure patients. Interventions included: telephone-based symptom monitoring (n = 5), automated monitoring of signs and symptoms (n = 1), and automated physiologic monitoring (n = 1). Two studies directly compared effectiveness of 2 or more forms of telemonitoring. Study quality and intervention type varied considerably. Six studies suggested reduction in all-cause and heart failure hospitalizations (14% to 55% and 29% to 43%, respectively) or mortality (40% to 56%) with telemonitoring. Of the 3 negative studies, 2 enrolled low-risk patients and patients with access to high quality care, whereas 1 enrolled a very high-risk Hispanic population. Studies comparing forms of telemonitoring demonstrated similar effectiveness. However, intervention costs were higher with more complex programs (8383 dollars per patient per year) versus less complex programs (1695 dollars per patient per year). CONCLUSION: The evidence base for telemonitoring in heart failure is currently quite limited. Based on the available data, telemonitoring may be an effective strategy for disease management in high-risk heart failure patients. PMID- 17339005 TI - Designs for mechanical circulatory support device studies. AB - BACKGROUND: There is increased interest in mechanical circulatory support devices (MCSDs), such as implantable left ventricular assist devices (LVADs), as "destination" therapy for patients with advanced heart failure. Because patient availability to evaluate these devices is limited and randomized trials have been slow in enrolling patients, a workshop was convened to consider designs for MCSD development including alternatives to randomized trials. METHODS AND RESULTS: A workshop was jointly planned by the Heart Failure Society of America and the US Food and Drug Administration and was convened in March 2006. One of the panels was asked to review different designs for evaluating new MCSDs. Randomized trials have many advantages over studies with no controls or with nonrandomized concurrent or historical controls. These advantages include the elimination of bias in the assignment of treatments and the balancing, on average, of known and unknown baseline covariates that influence response. These advantages of randomization are particularly important for studies in which the treatments may not differ from one another by a large amount (eg, a head-to-head study of an approved LVAD with a new LVAD). However, researchers have found it difficult to recruit patients to randomized studies because the number of clinical sites that can carry out the studies is not large. Also, there is a reluctance to randomize patients when the control device is considered technologically inferior. Thus ways of improving the design of randomized trials were discussed, and the advantages and disadvantages of alternative designs were considered. CONCLUSIONS: The panel concluded that designs should include a randomized component. Randomized designs might be improved by allowing the control device to be chosen before randomization, by first conducting smaller vanguard studies, and by allowing crossovers in trials with optimal medical management controls. With use of data from completed trials, other databases, and registries, alternative designs that include both a randomized component (eg, 2:1 allocation for new device versus control) and a nonrandomized component (eg, concurrent nonrandomized control, historical control, or a comprehensive cohort design) should be evaluated. This will require partnerships among academic, government, and industry scientists. PMID- 17339006 TI - A mechanistic interaction remains to be determined for elevated NTproBNP in heart failure patients receiving both an ACE inhibitor and aspirin. PMID- 17339008 TI - Tunable laser diodes for the 1250-1650 nm spectral range. AB - A series of tunable laser diodes was developed with emission wavelength in spectral range 1250-1650 nm. This paper describes the configuration and basic characteristics at temperatures from 5 to 80 degrees C. PMID- 17339009 TI - Nuclear envelope. PMID- 17339010 TI - Bees. PMID- 17339011 TI - Visual pigments of the platypus: a novel route to mammalian colour vision. PMID- 17339012 TI - The origin of male gametes. PMID- 17339013 TI - Animal cognition: bring me my spear. AB - Chimpanzees regularly hunt mammals, but use only their hands and teeth: for the first time, chimpanzees have now been found to make tools in order to spear mammalian prey. PMID- 17339014 TI - Meiotic pairing: a place to hook up. AB - At one end of each Caenorhabditis elegans chromosome is a locus required for meiotic crossing over. Recent studies have shown that these sites mediate chromosome pairing and synapsis during meiosis, and that each site contains binding sites for a non-canonical C2H2 zinc finger protein. PMID- 17339015 TI - Evolution: good males are bad females. AB - Manipulation of Drosophila melanogaster genomes allows large numbers of genes to be transmitted solely through males, thereby allowing selection to optimize flies for male function alone. It seems biasing phenotypes toward the male optima has serious fitness costs for females. PMID- 17339016 TI - Attention: control in the visual cortex. AB - A recent study in which the human visual cortex was directly stimulated to create visual percepts has shown that visual spatial attention can act directly on neural activity in sensory cortex without involving attentional modulation of subcortical visual inputs. PMID- 17339017 TI - Evolution and development: anchors away! AB - Developmental mechanisms can evolve even when the trait they produce does not, and the nematode vulva has become a model organ for detecting such "developmental system drift". A new study reveals what may be the very earliest stages of this process by experimentally modifying key vulval signaling pathways in different species of Caenorhabditis, and carefully quantifying the results. PMID- 17339018 TI - Object recognition: similar visual strategies of birds and mammals. AB - Behavioral testing has revealed that pigeons may use the same visual information sources as humans to discriminate between three-dimensional shapes. PMID- 17339019 TI - Cell migration: catapulting neurons from the ventricular zone? AB - In the developing vertebrate brain, newly born neurons migrate away from the proliferative zones. A new paper suggests that the initial phase of this migration may be propelled by the mechanical properties of the new neurons' processes rather than more conventional mechanisms of cell migration. PMID- 17339020 TI - Emotional memory: selective enhancement by sleep. AB - Never go to sleep on an argument: an old wives' tale or a scientifically proven technique for controlling the memories you store? Recent findings show that sleep selectively enhances emotional memories, creating a long-lasting and potentially traumatic representation of distressing experiences. PMID- 17339021 TI - BuMP-ing up insulin secretion by pancreatic beta cells. AB - While several transcription factors are known to increase insulin production and secretion, their therapeutic potential for treatment of type 2 diabetes remains unrealized. In this issue, Goulley et al. (2007) show that BMP signaling specifically regulates genes involved in insulin production and secretion and demonstrate that exogenous BMP4 administration augments glucose-stimulated insulin secretion in vivo. PMID- 17339022 TI - Sweet dreams for LXR. AB - Nuclear receptors (NRs) are transcription factors whose activities are modulated by the binding of small lipophilic ligands. The liver X receptors (LXRs) are an important pair of mammalian NRs that regulate lipid metabolism upon binding to cholesterol metabolites called oxysterols. A recent report that LXR activity is also regulated by binding to glucose (Mitro et al., 2007) expands the potential role of LXR in metabolic sensing and gene regulation. However, the hydrophilic nature of glucose and its low affinity for LXR present a challenge to central dogma about the nature of the NR-ligand interaction. PMID- 17339023 TI - The path to insulin resistance: paved with ceramides? AB - Obesity-associated, system-wide elevations in free fatty acids, tumor necrosis factor alpha, and glucocorticoids increase intracellular lipid metabolites and promote insulin resistance. In this issue, Holland et al. (2007) provide pharmacological and genetic evidence that ceramide plays a key role in the development of insulin resistance induced by these factors. PMID- 17339024 TI - STRA6, a cell-surface receptor for retinol-binding protein: the plot thickens. AB - How retinol (vitamin A) is taken up by cells has been an area of active research since the first report of a cell-surface receptor for retinol-binding protein (RBP) in the mid-1970s. Two recent reports, by Kawaguchi et al. (2007) and Pasutto et al. (2007), provide compelling data regarding the molecular identity and properties of a RBP receptor and open new research avenues for a better understanding of retinoid biology. PMID- 17339025 TI - Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. AB - Insulin resistance occurs in 20%-25% of the human population, and the condition is a chief component of type 2 diabetes mellitus and a risk factor for cardiovascular disease and certain forms of cancer. Herein, we demonstrate that the sphingolipid ceramide is a common molecular intermediate linking several different pathological metabolic stresses (i.e., glucocorticoids and saturated fats, but not unsaturated fats) to the induction of insulin resistance. Moreover, inhibition of ceramide synthesis markedly improves glucose tolerance and prevents the onset of frank diabetes in obese rodents. Collectively, these data have two important implications. First, they indicate that different fatty acids induce insulin resistance by distinct mechanisms discerned by their reliance on sphingolipid synthesis. Second, they identify enzymes required for ceramide synthesis as therapeutic targets for combating insulin resistance caused by nutrient excess or glucocorticoid therapy. PMID- 17339026 TI - Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. AB - Despite high leptin levels, most obese humans and rodents lack responsiveness to its appetite-suppressing effects. We demonstrate that leptin modulates NPY/AgRP and alpha-MSH secretion from the ARH of lean mice. High-fat diet-induced obese (DIO) mice have normal ObRb levels and increased SOCS-3 levels, but leptin fails to modulate peptide secretion and any element of the leptin signaling cascade. Despite this leptin resistance, the melanocortin system downstream of the ARH in DIO mice is over-responsive to melanocortin agonists, probably due to upregulation of MC4R. Lastly, we show that by decreasing the fat content of the mouse's diet, leptin responsiveness of NPY/AgRP and POMC neurons recovered simultaneously, with mice regaining normal leptin sensitivity and glycemic control. These results highlight the physiological importance of leptin sensing in the melanocortin circuits and show that their loss of leptin sensing likely contributes to the pathology of leptin resistance. PMID- 17339027 TI - Drosophila NPC1b promotes an early step in sterol absorption from the midgut epithelium. AB - The NPC1 family of proteins plays crucial roles in the intestinal absorption and intracellular trafficking of sterols. The Drosophila genome encodes two NPC1 homologs, one of which, NPC1a, is required for intracellular sterol trafficking in many tissues. Here we show that the other Drosophila NPC1 family member, NPC1b, is expressed in the midgut epithelium and that NPC1b is essential for growth during the early larval stages of development. NPC1b mutants are severely defective in sterol absorption, and the midgut epithelium of NPC1b mutants is deficient in sterols and sterol trafficking intermediates. By contrast, NPC1a mutants absorb sterols more efficiently than wild-type animals, and, unexpectedly, NPC1b;NPC1a double mutants absorb sterols as efficiently as wild type animals. Together, these findings suggest that NPC1b plays an early role in sterol absorption, although sterol absorption continues at high efficiency through an NPC1a- and NPC1b-independent mechanism under conditions of impaired intracellular sterol trafficking. PMID- 17339028 TI - BMP4-BMPR1A signaling in beta cells is required for and augments glucose stimulated insulin secretion. AB - Impaired glucose-stimulated insulin secretion (GSIS) and perturbed proinsulin processing are hallmarks of beta cell dysfunction in type 2 diabetes. Signals that can preserve and/or enhance beta cell function are therefore of great therapeutic interest. Here we show that bone morphogenetic protein 4 (Bmp4) and its high-affinity receptor, Bmpr1a, are expressed in beta cells. Mice with attenuated BMPR1A signaling in beta cells show decreased expression of key genes involved in insulin gene expression, proinsulin processing, glucose sensing, secretion stimulus coupling, incretin signaling, and insulin exocytosis and develop diabetes due to impaired insulin secretion. We also show that transgenic expression of Bmp4 in beta cells enhances GSIS and glucose clearance and that systemic administration of BMP4 protein to adult mice significantly stimulates GSIS and ameliorates glucose tolerance in a mouse model of glucose intolerance. Thus, BMP4-BMPR1A signaling in beta cells plays a key role in GSIS. PMID- 17339029 TI - A cis-element in the 5' untranslated region of the preproinsulin mRNA (ppIGE) is required for glucose regulation of proinsulin translation. AB - Insulin production in pancreatic beta cells is predominantly regulated through glucose control of proinsulin translation. Previously, this was shown to require sequences within the untranslated regions (UTRs) of the preproinsulin (ppI) mRNA. Here, those sequences were found to be sufficient for specific glucose-regulated proinsulin translation. Furthermore, an element 40-48 bp from the 5' end of the ppI mRNA specifically bound a factor present in islets of Langerhans. Glucose responsive factor binding to this cis-element exhibited temporal and glucose concentration-dependent patterns that paralleled proinsulin biosynthesis. Mutating this cis-element abolished the ability of ppI mRNA UTRs to confer glucose regulation upon translation. Like the rat 5'UTR, the human ppI 5'UTR conferred glucose regulation of translation. However alternative splicing of the human 5'UTR that disrupts the cis-element abolished glucose-regulated translation. These data indicate that glucose regulation of cis-element/trans acting factor interaction is a key component of the mechanism by which glucose regulates insulin production. PMID- 17339030 TI - Covalent surface chemistry gradients for presenting bioactive peptides. AB - The activation of surfaces by covalent attachment of bioactive moieties is an important strategy for improving the performance of biomedical materials. Such techniques have also been used as tools to study cellular responses to particular chemistries of interest. The creation of gradients of covalently bound chemistries is a logical extension of this technique. Gradient surfaces may permit the rapid screening of a large range of concentrations in a single experiment. In addition, the biological response to the gradient itself may provide new information on receptor requirements and cell signaling. The current work describes a rapid and flexible technique for the covalent addition of bioactive peptide gradients to a surface or gel and a simple fluorescence technique for assaying the gradient. In this technique, bioactive peptides with a terminal cysteine are bound via a heterobifunctional coupling agent to primary amine-containing surfaces and gels. A gradient in the coupling agent is created on the surfaces or gels by varying the residence time of the coupling agent across the surface or gel, thereby controlling the extent of reaction. We demonstrate this technique using poly(l-lysine)-coated glass surfaces and fibrin gels. Once the surface or gel has been activated by the addition of the coupling agent gradient, the bioactive peptide is added. Quantitation of the gradient is achieved by measuring the reaction kinetics of the coupling agent with the surface or gel of interest. This can be done either by fluorescently labeling the coupling agent (in the case of surfaces) or by spectrophotometrically detecting the release of pyridine-2-thione, which is produced when the thiol-reactive portion of the coupling agent reacts. By these methods, we can obtain reasonably precise estimates for the peptide gradients without using expensive spectroscopic or radiolabeling techniques. Validation with changes in fibroblast cell migration behavior across a bioactive peptide gradient illustrates preservation of peptide function as well as the usefulness of this technique. PMID- 17339031 TI - Site-specific transfer of an intact beta-globin gene cluster through a new targeting vector. AB - The ideal gene-therapy vector for treating genetic disorders should deliver intact therapeutic genes and their essential regulatory elements into the specific "safe genomic site" and realize long-term, self-regulatory expression. For beta-thalassemia gene therapy, viral vectors have been broadly used, but the accompanying insertional mutation and immunogenicity remain problematic. Hence, we aimed to develop new non-viral vectors that are efficient and safe in treating diseases. As previous studies have demonstrated that physiological expression of beta-globin genes requires both a 5' locus control region and 3' specific elements, we constructed a new human chromosome-derived targeting vector to transfer the intact beta-globin gene cluster into K562 cells. The whole beta globin gene cluster was precisely integrated into the target site and expressed in a self-regulatory pattern. The results proved that the human chromosome derived vector was specifically targeted to the human genome and this could provide a novel platform for further gene therapy research. PMID- 17339032 TI - Conserved elements within first intron of aquaporin-5 (Aqp5) function as transcriptional enhancers. AB - A 4.3 kb rat aquaporin-5 (Aqp5) promoter that directs lung and salivary cell specific expression in vitro directs low level expression of a GFP reporter in lungs of transgenic mice. Alignment of rat, mouse, and human AQP5 genomic sequences identified a highly conserved region in the 3' portion of intron 1, here termed ci1. To investigate the role of ci1 in Aqp5 expression, transient transfections were undertaken in AQP5-expressing mouse lung epithelial (MLE-15) and rat salivary (Pa-4) cells and AQP5-non-expressing NIH/3T3 cells. A 536 bp ci1 fragment enhanced transcriptional activity of the rat Aqp5 minimal promoter specifically in MLE-15 cells in an orientation-independent manner. Enhancer activity was Aqp5 promoter-specific, since no increase in activity was detected with the TK promoter. These results suggest that expression of transgenes in mouse lungs under direction of the 4.3 kb rat Aqp5 promoter may be augmented by inclusion of ci1 in transgenic constructs. PMID- 17339033 TI - Hydration pattern of A4T4 and T4A4 DNA: a molecular dynamics study. AB - Hydration pattern and energetics of 'A-tract' containing duplexes have been studied using molecular dynamics on 12-mer self-complementary sequences 5' d(GCA4T4GC)-3' and 5'-d(CGT4A4CG)-3'. The structural features for the simulated duplexes showed correlation with the corresponding experimental structures. Analysis of the hydration pattern confirmed that water network around the simulated duplexes is more conformation specific rather than sequence specific. The calculated heat capacity change upon duplex formation showed that the process is entropically driven for both the sequences. Furthermore, the theoretical free energy estimates calculated using MMPBSA approach showed a higher net electrostatic contribution for A4T4 duplex formation than for T4A4, however, energetically both the duplexes are observed to be equally stable. PMID- 17339034 TI - Critical residues of alphaX I-domain recognizing fibrinogen central domain. AB - Integrin alphaXbeta2 (CD11c/CD18), which binds several ligands such as fibrinogen and iC3b, has important roles in leukocyte functions including phagocytosis and migration. Establishment of structure and functional relationship in alphaX I domain, which is a ligand-binding moiety, is important in understanding leukocyte biology and integrin function. Previously we showed that two loops (alpha3 alpha4, betaD-alpha5) around a ligand-binding face of alphaX I-domain are important for the binding of the fibrinogen molecule. In this study, we took the further step of identifying critical residues in these loops and in a supportive loop (betaF-alpha7) for fibrinogen fragment E, the central domain of fibrinogen. The residues S(199) and Q(202) in the alpha3-alpha4 loop and K(243), Y(250) in the betaD-alpha5 loop are critical for the ligand. The residues K(242), D(249), K(251), and D(252) are important but less critical for fibrinogen fragment E. The involvement of the residues in the 3-dimensional model of the I-domain suggests that several amino acid sequences in fibrinogen fragment E are responsible for alphaX I-domain. Sequence comparisons with alphaM I-domain reveal that most of the critical residues shown in alphaX I-domain are also conserved in alphaM and may have important roles in fibrinogen central domain recognition in alphaM I domain as well. PMID- 17339035 TI - Knowledge-based localization of hippocampus in human brain MRI. AB - We present a novel and efficient method for localization of human brain structures such as hippocampus. Landmark localization is important for segmentation and registration. This method follows a statistical roadmap, consisting of anatomical landmarks, to reach the desired structures. Using a set of desired and undesired landmarks, identified on a training set, we estimate Gaussian models and determine optimal search areas for desired landmarks. The statistical models form a set of rules to evaluate the extracted landmarks during the search procedure. When applied on 900 MR images of 10 epileptic patients, this method demonstrated an overall success rate of 83%. PMID- 17339036 TI - Prenatal examination behavior of Southeast Asian pregnant women in Taiwan: a questionnaire survey. AB - BACKGROUND: There is growing concern about the factors affecting the prenatal examinations of immigrant women. OBJECTIVES: The purpose of this study was to examine the relationships between the knowledge of pregnancy, attitude toward pregnancy and experience of medical services, and prenatal examination behavior of pregnant Southeast Asian women in Taiwan. DESIGN: This was a cross-sectional study with a structured questionnaire administered to participants. SETTING: Participants were recruited from the community health centers in Kaohsiung County, Taiwan. PARTICIPANTS: The sampling criteria were as follows: each subject was to (a) have come from a Southeast Asian country, (b) be over 28 weeks pregnant to less than one year postpartum, (c) be able to communicate either in Mandarin or Taiwanese, and (d) be willing to participate in the research after hearing an explanation of it. As a result, 140 participants were recruited. A total of 132 participants completed the questionnaire and were used for data analysis. METHODS: The participants completed structured questionnaires, which included the Demographic Inventory Scale, Knowledge of Pregnancy Scale, Attitudes toward Pregnancy Scale, Experience of Medical Services Scale and the Prenatal Examination Behavior Scale. RESULTS: Findings show that 80.3% of the subjects attended their first-time prenatal examination during the first trimester and 59.1% of the subjects evaluated their prenatal examinations as being adequate. Their attitude toward childbearing was significantly correlated with their prenatal examination behavior, including the initial time of prenatal examination and frequencies of prenatal examinations during pregnancy. Positive attitudes toward childbearing and prenatal examination, and the number of years spent in Taiwan were all significant predictive factors of frequencies of prenatal examinations during pregnancy. The findings of this study can not only help healthcare professionals understand the prenatal examination behavior and related factors of the participants, but also provide guidance to healthcare professionals as they assist these pregnant Southeast Asian women in Taiwan in developing childbearing and family plans. CONCLUSION: The attitude toward childbearing of the participants was significantly correlated with their prenatal examination behavior. They require professional help in seeking out appropriate medical services that will improve their healthcare quality during pregnancy. PMID- 17339037 TI - Ion chromatographic investigation of the ion-exchange properties of microdisperse sintered nanodiamonds. AB - The possibility of using sintered diamonds as a stationary phase in ion chromatography has been evaluated. Bare sintered synthetic nanodiamonds demonstrated the properties of a weak cation-exchanger. The observed ion-exchange selectivity is similar to carboxylic type cation-exchangers. The regularities of retention of alkali, alkaline-earth and transition metal ions on a column packed with sintered nanodiamonds in dilute nitric acid were studied and the occurrence of chelating properties was noted. For the first time chromatographic separations of model mixtures of cations on diamonds have been obtained. PMID- 17339038 TI - Method to predict and compare the influence of the particle size on the isocratic peak capacity of high-performance liquid chromatography columns. AB - A kinetic plot based method has been used to experimentally predict the optimal particle size yielding the maximal isocratic peak capacity in a given analysis time. Applying the method to columns of three different manufacturers and characterizing them by separating a 4-component paraben mixture at 30 degrees C, it was consistently found that the classical 3 and 3.5 microm particles provide the highest peak capacity for typical isocratic separation run times between 30 and 60 min when operating the columns at a conventional pressure of 400 bar. Even at 1000 bar, the sub-2 microm particles only have a distinct advantage for runs lasting 30 min or less, while for runs lasting 45 min or longer the 3 and 3.5 microm again are to be preferred. This finding points at the advantage for high resolution separations that could be obtained by producing 3 and 3.5 microm particle columns that can be operated at elevated pressures. PMID- 17339039 TI - Characterization of antihistamine-human serum protein interactions by capillary electrophoresis. AB - An important topic in the drug discovery and development process is the role of drug binding to plasma proteins. In this paper the characterization of the interaction between antihistamines (cationic drugs) towards human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP) under physiological conditions by capillary electrophoresis-frontal analysis is presented. Furthermore, the binding of these drugs to all plasma proteins is evaluated by using ultrafiltration and capillary electrophoresis. Antihistamines present a wide-ranging behaviour with respect to their affinities towards plasma proteins. Orphenadrine, phenindamine, tripelenamine and tripolidine principally bind to HSA; carbinoxamine, dimetindene and etintidine principally bind to AGP; brompheniramine, chlorpheniramine and ranitidine present an important binding to lipoproteins and/or globulins and finally, chlorcyclizine, cinarizine, cyclizine, doxylamine, hydroxyzine, perphenazine and terfenadine do not bind to lipoproteins and/or globulins but bind to HSA and AGP in different extension. The interaction of antihistamines with HSA is determined by the hydrophobicity (direct relationship) and the polar surface area (indirect relationship) of the compounds. The steric parameters and hydrogen bonding character of compounds seems to be related with the binding of antihistamines to AGP. The antihistamine-HSA affinity constants were evaluated and the K(1) values ranged from 7 x 10(2)M(-1) (for doxylamine) to 4 x 10(4)M(-1) (for phenindamine). PMID- 17339040 TI - Measurement uncertainty arising from trueness of the analysis of two endocrine disruptors and their metabolites in environmental samples. Part I: ultrasonic extraction from diverse sediment matrices. AB - The validation of preconcentration strategies for the simultaneous determination of two endocrine disrupting compounds (EDCs) and their metabolites present in the aquatic environment including natural waters and freshwater sediments as well as the estimation of uncertainty arising from trueness using fully nested experimental designs are presented in a series of two papers. In this work, we present Part I of our ongoing study, the validation of an analytical method based on ultrasonic extraction of the target analytes from various freshwater sediments and the estimation of the method measurement uncertainty. The selected endocrine disruptors included two widely used herbicides, diuron (1-(3,4-dichlorophenyl) 3,3-dimethylurea) and linuron (3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea) and their common degradation products namely, 3,4-dichloroaniline (3,4-DCA), 1-(3,4 dichlorophenyl) urea (DCPU) and 1-(3,4-dichlorophenyl)-3-methylurea (DCPMU). A high-performance liquid chromatography system coupled to UV-diode array detector (HPLC/UV-DAD) was used for the target analytes quantification. A fully nested experimental design was applied to study the measurement uncertainty arising from trueness by estimating proportional bias (in terms of recovery). The overall recoveries, that is, those determined by the nested experiments were in the range of 59.5-85.1%, except 3,4-DCA for which a low overall recovery of 29.0% was observed. The analytical method was shown to be linear over the studied range of concentrations (5-100 microg/kg), exhibiting satisfactory repeatability and reaching limits of detection usually in the 0.6-4.6 microg/kg range on dry sediment basis. The method used permitted the determination of the target EDCs and their metabolites in sediment samples collected from selected study stations in the region of Epirus (N.W. Greece) at the concentration levels demanded by current legislation. PMID- 17339041 TI - Set-up and evaluation of interlaboratory studies. AB - Interlaboratory comparison by means of method performance precision and bias studies and proficiency testing schemes are described. The set-up of the experiments as well as the evaluation of the data by means of graphical and statistical methods are considered. The use of interlaboratory data for the estimation of measurement uncertainty is also addressed. PMID- 17339042 TI - Determination of the threshold odor concentration of main odorants in essential oils using gas chromatography-olfactometry incremental dilution technique. AB - An essential oil, obtained by steam distillation of Clinopodium tomentosum (Kunth) Govaerts (Lamiaceae), collected in Ecuador, was analyzed by gas chromatography-olfactometry (GC-O) and GC-MS techniques. To our knowledge, the composition of this essential oil is described here for the first time, both from the chemical and olfactometric viewpoints. A preliminary analysis by GC-MS and using Kovats' retention indexes, lead to characterize and quantify the oil constituents, while GC-O was then applied for the identification of the main odorants. By the incremental dilution method (AEDA, CHARM Analysis), applied to the GC-O technique, the flavor dilution (FD) chromatogram was obtained. In order to calculate the TOC values of the main odorants, the relationship between the odorant concentration at the sniffing port and that one in the injected solution was established. This relationship was calculated by comparing the injected amount with the TOC value of a reference compound (limonene), obtained by dynamic dilution olfactometry. A good agreement was found between calculated and measured TOC values of few odorants. PMID- 17339043 TI - The development of expert face processing: are infants sensitive to normal differences in second-order relational information? AB - Sensitivity to second-order relational information (i.e., spatial relations among features such as the distance between eyes) is a vital part of achieving expertise with face processing. Prior research is unclear on whether infants are sensitive to second-order differences seen in typical human populations. In the current experiments, we examined whether infants are sensitive to changes in the space between the eyes and between the nose and the mouth that are within the normal range of variability in Caucasian female faces. In Experiment 1, 7-month olds detected these changes in second-order relational information. Experiment 2 extended this finding to 5-month-olds and also found that infants detect second order relations in upright faces but not in inverted faces, thereby exhibiting an inversion effect that has been considered to be a hallmark of second-order relational processing during adulthood. These results suggest that infants as young as 5 months are sensitive to second-order relational changes that are within the normal range of human variability. They also indicate that at least rudimentary aspects of face processing expertise are available early in life. PMID- 17339044 TI - Implicit integration in a case of integrative visual agnosia. AB - We present a case (SE) with integrative visual agnosia following ischemic stroke affecting the right dorsal and the left ventral pathways of the visual system. Despite his inability to identify global hierarchical letters [Navon, D. (1977). Forest before trees: The precedence of global features in visual perception. Cognitive Psychology, 9, 353-383], and his dense object agnosia, SE showed normal global-to-local interference when responding to local letters in Navon hierarchical stimuli and significant picture-word identity priming in a semantic decision task for words. Since priming was absent if these features were scrambled, it stands to reason that these effects were not due to priming by distinctive features. The contrast between priming effects induced by coherent and scrambled stimuli is consistent with implicit but not explicit integration of features into a unified whole. We went on to show that possible/impossible object decisions were facilitated by words in a word-picture priming task, suggesting that prompts could activate perceptually integrated images in a backward fashion. We conclude that the absence of SE's ability to identify visual objects except through tedious serial construction reflects a deficit in accessing an integrated visual representation through bottom-up visual processing alone. However, top down generated images can help activate these visual representations through semantic links. PMID- 17339045 TI - Smoking, smoking cessation, and use of smoking cessation aids and support services in South Derbyshire, England. AB - OBJECTIVES: To describe smoking behaviour, motivation to quit and quit rates, and the effect of advice and support for smoking cessation among smokers from more and less disadvantaged socio-economic groups in South Derbyshire, a mixed urban and rural area of central England. STUDY DESIGN: Cross-sectional study. METHODS: A cross-sectional study with a random, stratified sample of people aged 25-44 years and people aged 65-74 years with over-sampling of populations living in disadvantaged areas. Main outcome measures included the proportion of smokers wishing to quit and quitting in the last year; reported advice to quit from family and friends and health professionals; and awareness and use of NHS smoking cessation services. RESULTS: Over half of smokers aged 25-44 years, about one third of women smokers and 40% of male smokers aged 65-74 years wished to quit. This varied little by socio-economic status. Quit rates were generally lower among smokers of lower socio-economic status (SES), especially among people aged 25-44 years. Smokers of lower SES reported slightly less advice to quit from family and friends, and more so from health professionals. Awareness and use of cessation services was about 30% and 5%, respectively, among smokers and recent quitters. Awareness varied little but accessing services was generally higher among smokers of lower SES. CONCLUSIONS: Despite evidence that health professionals and cessation services were targeting smokers with lower SES and of similar motivation to quit, quit rates were lower. Broader tobacco control interventions targeting the social and environmental contexts that create and maintain socio-economic differentials in smoking are required. PMID- 17339046 TI - Mechanical sludge disintegration for the production of carbon source for biological nutrient removal. AB - The primary driver for a successful biological nutrient removal is the availability of suitable carbon source, mainly in the form of volatile fatty acids (VFA). Several methods have been examined to increase the amount of VFAs in wastewater. This study investigates the mechanism of mechanical disintegration of thickened surplus activated sludge by a deflaker technology for the production of organic matter. This equipment was able to increase the soluble carbon in terms of VFA and soluble chemical oxygen demand (SCOD) with the maximum concentration to be around 850 and 6530 mgl(-1), for VFA and SCOD, respectively. The particle size was reduced from 65.5 to 9.3 microm after 15 min of disintegration with the simultaneous release of proteins (1550 mgl(-1)) and carbohydrates (307 mgl(-1)) indicating floc disruption and breakage. High performance size exclusion chromatography investigated the disintegrated sludge and confirmed that the deflaker was able to destroy the flocs releasing polymeric substances that are typically found outside of cells. When long disintegration times were applied (>or=10 min or >or=9000 kJkg(-1)TS of specific energy) smaller molecular size materials were released to the liquid phase, which are considered to be found inside the cells indicating cell lysis. PMID- 17339047 TI - Increased expression of ADAM33 and ADAM8 with disease progression in asthma. AB - BACKGROUND: ADAM33, a disintegrin and metalloproteinase 33 gene, has been identified as a risk factor for asthma and bronchial hyperresponsiveness and has been postulated as a gene for airway remodeling. ADAM8 is strongly induced by allergens and T(H)2 cytokines in the lung in experimental asthma. OBJECTIVES: To assess the importance of these genes in asthma pathogenesis and to investigate whether expression relates to disease severity or deterioration in lung function, we measured the mRNA and protein expression of both genes in bronchial biopsies of subjects with asthma and control subjects. METHODS: RNA was extracted from frozen endobronchial biopsies of mild, moderate, and severe adults with asthma and controls. Subjects with moderate and severe asthma were taking corticosteroids. The mRNA transcript of both genes was measured by real time RT PCR using specific primers. Protein expression was examined by immunohistochemistry on paraffin sections. RESULTS: ADAM33 mRNA expression was significantly higher in both moderate and severe asthma compared with mild asthma (P < .05) and controls. Immunostaining for ADAM33 was increased in the epithelium, submucosal cells, and smooth muscle in severe asthma compared with mild disease and controls. ADAM8 mRNA expression was significantly increased in all asthma groups compared with controls. Increased inflammatory cells stained positive for ADAM8 in both moderate (P < .05) and severe asthma (P < .005) compared with mild disease. CONCLUSIONS: These results demonstrate increased expression of both ADAM genes as asthma severity increases. CLINICAL IMPLICATIONS: These genes may contribute to the remodeling process that occurs with asthma progression and may have implications for future treatment in severe disease. PMID- 17339048 TI - Nanocomposites with Ca and PO4 release: effects of reinforcement, dicalcium phosphate particle size and silanization. AB - OBJECTIVES: Nanoparticles of dicalcium phosphate anhydrous (DCPA) were synthesized in our laboratory for the first time and incorporated into a dental resin. Our goal was to develop a mechanically strong dental composite that has Ca and PO(4) ion release to combat tooth caries, and to investigate the effects of whisker reinforcement, DCPA particle size and silanization. METHODS: DCPA nanoparticles and two larger DCPA particles were used with nano-silica-fused whiskers as fillers in a resin matrix. Composite mechanical properties were measured via three-point flexure, and the release of Ca and PO(4) ions were measured versus time. RESULTS: Using DCPA nanoparticles with a diameter of 112nm, the composite at a DCPA:whisker mass ratio of 1:1 had a flexural strength (mean+/ S.D.; n=5) of (112+/-17)MPa, not significantly different from (112+/-14)MPa of a commercial non-releasing composite; both were higher than (29+/-7)MPa for the composite at DCPA:whisker of 1:0 (p<0.05). The composite with DCPA particle size of 112nm released Ca to a concentration of 0.85mmol/L and PO(4) of 3.48mmol/L, higher than Ca of 0.67mmol/L and PO(4) of 1.11mmol/L using DCPA with 12microm particle size (p<0.05). Silanization of DCPA increased the composite strength at DCPA:whisker of 1:0 compared to that without silanization, but decreased the Ca and PO(4) release (p<0.05). Increasing the DCPA particle surface area increased the Ca and PO(4) release. SIGNIFICANCE: Decreasing the DCPA particle size increased the Ca and PO(4) release; whisker reinforcement increased the composite strength by two- to three-fold. The nano DCPA-whisker composites, with high strength and Ca and PO(4) release, may provide the needed, unique combination of stress-bearing and caries-inhibiting capabilities. PMID- 17339050 TI - Nanostructured magnetizable materials that switch cells between life and death. AB - Development of biochips containing living cells for biodetection, drug screening and tissue engineering applications is limited by a lack of reconfigurable material interfaces and actuators. Here we describe a new class of nanostructured magnetizable materials created with a femtosecond laser surface etching technique that function as multiplexed magnetic field gradient concentrators. When combined with magnetic microbeads coated with cell adhesion ligands, these materials form microarrays of 'virtual' adhesive islands that can support cell attachment, resist cell traction forces and maintain cell viability. A cell death (apoptosis) response can then be actuated on command by removing the applied magnetic field, thereby causing cell retraction, rounding and detachment. This simple technology may be used to create reconfigurable interfaces that allow users to selectively discard contaminated or exhausted cellular sensor elements, and to replace them with new living cellular components for continued operation in future biomedical microdevices and biodetectors. PMID- 17339049 TI - Effect of genipin, a naturally occurring crosslinker on the properties of kappa carrageenan. AB - Genipin-fixed kappa-carrageenan was prepared in ambient conditions in aqueous solution using genipin, a naturally occurring crosslinker with kappa-carrageenan (kappaC). The crosslinked kappaC showed the greatest swelling capacity in acidic medium having pH 1.2 when compared to those in neutral and alkaline media. Enhanced stability of the crosslinked product with respect to the non-modified kappaC was confirmed by degradation studies in Ringer's solution, rheological and thermogravimetric measurements. Genipin fixation of kappaC was confirmed by measuring the bulk density, true density, pore volume, porosity, intrinsic viscosity, UV absorbance and optical rotation of the crosslinked kappaC, and as well as by optical microscopy, SEM, and MS/MS studies. The crosslinked product may be useful as super absorbent and sustained release formulation in biomedical applications. PMID- 17339051 TI - The effect on bone regeneration of a liposomal vector to deliver BMP-2 gene to bone grafts in peri-implant bone defects. AB - Successful bone-implant osseointegration in large peri-implant bone defects is often difficult, even through autologous bone grafting. Recently, cell-mediated regional gene therapy was introduced to deliver potent morphogens or growth factors in regenerative medicine. We applied liposomal vectors carrying bone morphogenetic protein (BMP)-2 cDNA directly into freshly created peri-implant bone defects on pig calvariae, with or without autologous bone graft. The BMP-2 gene was efficiently introduced into immigrating cells and trabecular cells lining the marginal bone surrounding the bony defect. After 1 week, abundant BMP 2 protein was detected throughout the peri-implant bone defect by immunohistochemistry. At 4 weeks, BMP-producing cells were still present in the defect and peri-implant area, which significantly enhanced new bone formation, compared with the control groups. Interestingly within a week of BMP-2 gene delivery with bone grafts, most osteoblastic cells lining the grafted bone chips also produced BMP-2. Particulated bone was immediately reorganized into newly formed trabecular bone. Grafted bone without BMP-2 gene delivery was still scattered and new bone matrix formation was not detected until 4 weeks after bone grafting. In conclusion, direct application of the BMP-2 gene using a liposomal vector enhanced bone regeneration in a bony defect and gene delivery combined with bone graft could induce a rapid osseointegration of the bone-implant interface at earlier stage. PMID- 17339052 TI - Synergy of CpG oligodeoxynucleotide and double-stranded RNA (poly I:C) on nitric oxide induction in chicken peripheral blood monocytes. AB - Toll-like receptors (TLRs) recognize microbial components and initiate the innate immune responses that control microbial infections. We have investigated the innate immune response of chicken monocytes to ligands of TLR3 and TLR9, poly I:C (an analog of viral double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide) by measuring the induction of nitric oxide (NO) synthesis in chicken monocytes. Our results show that poly I:C and CpG-ODN synergized the induction of NO. When stimulated separately, CpG-ODN induced significant NO production in the chicken monocytes; whereas, poly I:C stimulated very little NO production. In combination, CpG-ODN and poly I:C induced significantly higher level of NO in chicken monocytes than either agonist alone. The addition of poly I:C prior to or simultaneously with CpG-ODN was required for the synergy. No synergistic effects on NO production were observed when monocytes were stimulated with combinations of CpG-ODN or poly I:C with other TLR agonists. Unlike chicken monocytes, cells of a chicken macrophage cell line, HD11, were readily stimulated to produce NO by both CpG-ODN and poly I:C with no synergism on NO induction when HD11 cells were stimulated by a combination of CpG-ODN and poly I:C. Using a pharmacological inhibitor, we also demonstrated that double-stranded RNA dependent protein kinase (PKR) is indispensable for stimulation of NO production by CpG-ODN alone or in combination with poly I:C in both chicken peripheral blood monocytes and HD11 macrophage cells. Our results show that a combination of bacterial DNA and dsRNA induces an enhanced inflammatory immune response that has both antiviral and antibacterial activity in primary chicken monocytes. PMID- 17339053 TI - Flawed TandAb production. PMID- 17339054 TI - Sveinsson chorioretinal atrophy/helicoid peripapillary chorioretinal degeneration: first histopathology report. AB - PURPOSE: To report the histopathologic features in an eye with Sveinsson chorioretinal atrophy (SCRA), also termed helicoid peripapillary chorioretinal degeneration, for the first time. PARTICIPANT: An 82-year-old woman clinically and genetically confirmed to have SCRA. DESIGN: Examination of an eye obtained after death. METHOD: Light microscopic examination of an eye of an 82-year-old woman documented to have SCRA since the age of 10 years. MAIN OUTCOME MEASURE: The findings in ocular tissues were determined by light microscopy. RESULTS: In the most advanced areas of chorioretinal atrophy, the sensory retina, retinal pigment epithelium (RPE), choriocapillaris, and choroid were absent. In the transition between affected and unaffected areas, the RPE and the outer segments of the photoreceptors only were affected. The optic nerve was smaller than normal, but well myelinated. Other ocular tissues retained a relatively normal appearance for a patient who had died at this age. CONCLUSIONS: The mildest and presumably earliest morphologic changes involved the photoreceptor outer segments, the RPE, and choriocapillaris in this progressive degenerative disease of the retina and choroid. PMID- 17339055 TI - An alteration in the levels of populations of CD4+ Treg is in part responsible for altered cytokine production by cells of aged mice which follows injection with a fetal liver extract. AB - We have shown previously that a fetal sheep liver extract (FSLE) containing significant quantities of fetal ovine gamma globin chain (Hbgamma) and LPS injected into aged (>20 months) mice could reverse the altered polarization (increased IL-4 and IL-10 with decreased IL-2 and IFNgamma) in cytokine production seen from ConA stimulated lymphoid cells of those mice. The mechanism(s) behind this change in cytokine production were not previously investigated. We report below that aged mice show a >60% decline in numbers and suppressive function of both CD4(+)CD25(+)Foxp3(+) Treg and so-called Tr3 (CD4(+)TGFbeta(+)), and that their number/function is restored to levels seen in control (8-week-old) mice by FSLE. In addition, on a per cell basis, CD4(+)CD25( )Treg from aged mice were >4-fold more effective in suppression of proliferation and IL-2 production from ConA-activated lymphoid cells of a pool of CD4(+)CD25( )T cells from 8-week-old mice than similar cells from young animals, and this suppression by CD25(-)T cells was also ameliorated following FSLE treatment. Infusion of anti-TGFbeta and anti-IL-10 antibodies in vivo altered Treg development following FSLE treatment, and attenuated FSLE-induced alterations in cytokine production profiles. PMID- 17339056 TI - Neuronal death: where does the end begin? AB - Neurodegenerative disorders involve death of cell bodies, axons, dendrites and synapses, but it is surprisingly difficult to determine the spatiotemporal sequence of events and the causal relationships among these events. Neuronal compartments often crucially depend upon one another for survival, and molecular defects in one compartment can trigger cellular degeneration in distant parts of the neuron. Here, we consider the novel approaches used to understand these biologically complex and technically challenging questions in amyotrophic lateral sclerosis, spinal muscular atrophy, glaucoma, Alzheimer's disease, Parkinson's disease and polyglutamine disorders. We conclude that there is partial understanding of what degenerates first and why, but that controversy remains the rule not the exception. Finally, we highlight strategies for resolving these fundamental issues. PMID- 17339057 TI - Photoperiod alters affective responses in collared lemmings. AB - This study examined photoperiodic regulation of affective behaviours in collared lemmings (Dicrostonyx groenlandicus). Male and female lemmings were housed in either long (LD 22:2), intermediate (LD 16:8), or short days (LD 8:16) for 9 weeks. Exposure to short days induced moult to a winter pelage and gonadal regression in male, but not female, lemmings. Lemmings housed in long days reduced anxiety-like responses in the elevated plus maze. Depressive-like behaviours were decreased in the intermediate photoperiod relative to other photoperiod groups. PMID- 17339058 TI - A comparison of the behavior of C57BL/6 and C57BL/10 mice. AB - Selection of an appropriate animal model is a crucial first step in many research programs. The C57BL/6 (B6) mouse is the most widely used inbred mouse strain in biomedical research; this is particularly so in behavioral studies. However, there are several C57BL substrains, all derived from common ancestors. C57BL/10 (B10) mice are superficially almost identical to B6 mice in appearance and behavior and widely used in inflammation and immunology research, yet rarely in behavioral studies. The present study assessed the comparability of behavioral results from these two strains, to determine whether they could be used interchangeably in future behavioral experiments. The results showed that the behavior of B6 mice clearly differed from that of B10 mice: in tests of cognition, species-typical behaviors, and motor coordination the B6 strain performed better. Consequently, B6 mice will probably remain the preferred choice for behavioral studies. Interpretation of results derived from the B10 strain should take into account its particular behavioral characteristics. PMID- 17339059 TI - The impact of the goitrogen 6-propylthiouracil (PTU) on West-African clawed frog (Xenopus tropicalis) exposed during metamorphosis. AB - This study investigated the suitability of using tadpoles of the West-African clawed frog (Xenopus tropicalis) for studying adverse effects on the thyroid hormone system after chemical exposure. Tadpoles were exposed to the thyroxine synthesis inhibitor 6-propylthiouracil (PTU) at concentrations between 2-75mg/L during 14 days. After 5 and 14 days of exposure the developmental stage, hind limb length, body length and weight were measured. Moreover, histological measurements of the thyroid glands were performed after 14 days of exposure. These measurements included maximum thyroid cross-section area, follicular area and epithelial cell height. Tadpoles in the 75mg/L treatment were less developed and had shorter hind limb length than the control group after 14 days of exposure. No effects were recorded on these parameters at lower PTU concentrations. The histological measurements revealed clear dose-response relationships in both follicular cross-section area and epithelial cell height, with lowest observed effect concentrations (LOECs) recorded at 2 and 5mg/L, respectively. This study shows that X. tropicalis is a suitable species for detection of thyroid disrupting chemicals. Further, histopathological measurements of thyroid glands are more sensitive parameters compared with apical endpoints when studying adverse effects on thyroid hormone system caused by PTU exposure in X. tropicalis. PMID- 17339060 TI - Gender discrimination in the elderly and its impact on the elderly health. AB - The aim of this study was to determine gender discrimination and risk factors in the elderly population and to assess the impact of that discrimination on elderly health. One hundred and sixty-eight elderly individuals who were selected from the records by simple randomized sampling were enrolled in the study. Data were obtained by face-to-face interviews at the residence of the elderly individuals. Chi(2)-Analysis, t-test, Mann-Whitney U-test, and logistic regression were used for data analysis. 81.1% of the elderly were married and 40.5% were middle or high school graduates, and 93.9% of the subjects had at least one living child. It was determined that 51.7% of the females, and 21.3% of the males were exposed to negative gender discrimination. This discrimination was higher among women in all sub-groups. In fact, older women and elderly individuals with only primary school education or less were significantly more exposed to gender discrimination (p=0.008 and p=0.043, respectively). It was found that only economical variables were related to poor health status, without gender discrimination. Despite the fact that the freedom has been obtained in some areas such as participation in household decision-making and dressing, the patriarchal family structure and sexual inequality continue in older age. PMID- 17339061 TI - Liability, insurance and medical practice. AB - We test for effects of tort liability on the use of certain diagnostic procedures, where the health care providers' expected cost of litigation is proxied by the risk-sharing arrangements agreed with their insurers. 2SLS and GMM estimators are adopted to test for possible endogeneity of these risk-sharing arrangements. Our findings are consistent with the exercise of liability-induced discretion by hospitals, especially regarding use of costly diagnostic imaging procedures. Hospitals facing higher expected costs per claim as a consequence of higher deductibles used these tests more frequently, after controlling for activity levels and casemix. These results are consistent with hospitals reacting to the incentives provided by a clinical negligence compensation system. PMID- 17339062 TI - Rat leucine-rich protein binds and activates the promoter of the beta isoform of Ca2+/calmodulin-dependent protein kinase II gene. AB - We previously found the neuronal cell-type specific promoter and binding partner of the beta isoform of Ca(2+)/calmodulin-dependent protein kinase II (beta CaM kinase II) in rat brain [Donai, H., Morinaga, H., Yamauchi, T., 2001. Genomic organization and neuronal cell type specific promoter activity of beta isoform of Ca(2+)/calmodulin-dependent protein kinase II of rat brain. Mol. Brain Res. 94, 35-47]. In the present study, we purified a protein that binds specifically a promoter region of beta CaM kinase II gene from a nuclear extract of the rat cerebellum using DEAE-cellulose column chromatography, ammonium sulfate fractionation, gel filtration and polyacrylamide gel electrophoresis. The purified protein was identified as rat leucine-rich protein 157 (rLRP157) using tandem mass spectrometry. Then, we prepared its cDNA by reverse transcriptase polymerase chain reaction (RT-PCR) from poly(A)(+)RNA of rat cerebellum. The rLRP157 cDNA was introduced into mouse neuroblastomaxrat glioma hybrid NG108-15 cells, and cells stably expressing rLRP157 (NG/LRP cells) were isolated. Binding of rLRP157 with the promoter sequence was confirmed by electrophoretic mobility shift assay using nuclear extract of NG/LRP cells. A luciferase reporter gene containing a promoter of beta CaM kinase II was transiently expressed in NG/LRP cells. Under the conditions, the promoter activity was enhanced about 2.6-fold in NG/LRP cells as compared with wild-type cells. The expression of rLRP157 mRNA was paralleled with that of beta CaM kinase II in the adult and embryo rat brain detected by in situ hybridization. Nuclear localization of rLRP157 was confirmed using GFP-rLRP157 fusion protein investigated under a confocal microscope. These results indicate that rLRP157 is one of the proteins binding to, and regulating the activity of, the promoter of beta CaM kinase II. PMID- 17339063 TI - Co-expression of signaling proteins improves robustness of the bacterial chemotaxis pathway. AB - Biological systems are exposed to various perturbations that affect performance of the cellular networks, with stochastic variation in protein levels, or gene expression noise, being one of the major sources of intracellular perturbations. We recently used Escherichia coli chemotaxis as a model to analyze robustness against such noise and demonstrated theoretically and experimentally that a steady-state output of the pathway is robust against concerted variation in the levels of all chemotaxis proteins. However, our model predicted that the pathway topology does not confer much robustness against an uncorrelated variation in the protein levels. To test whether additional robustness features might be missing from our model, we compare here its predictions with an experimentally determined chemotactic performance under varying levels of individual proteins. Our data show that the pathway is indeed even more robust than predicted to two types of perturbations-the variation in the levels of the adaptation enzymes and a correlated expression of CheY and CheZ. Although the design features that are responsible for this higher robustness still remain to be understood, our results stress the importance of a robust design of both native and synthetic signaling networks. PMID- 17339064 TI - (2S,3S)-Oxirane-2,3-dicarboxylic acid: a privileged platform for probing human cysteine cathepsins. AB - The notion that human cysteine cathepsins contribute only to general protein turnover within the lysosomes has changed in the last decade in a substantial manner. A continuously growing number of data accumulated in different fields of life sciences revealed that these enzymes are involved in a variety of pivotal physiological processes. To investigate these particular fraction of proteolytical activity of the human degradome even in a complex cellular environment, chemical probes that covalently label the corresponding proteases proved to be versatile tools. (2S,3S)-Oxirane-2,3-dicarboxylic acid provides an ideal platform for the design of such probing systems. Depending on the complexity of the attached recognition elements, either the activity of the entire group of human cysteine cathepsins or individual members can be detected. PMID- 17339065 TI - Angiotensin receptor blockade in diabetic renal disease--focus on candesartan. AB - Prevention and regression of diabetic renal disease can be obtained through the combination of strict blood pressure control, which frequently requires the combination of different antihypertensive drugs, with tight glycaemic control. Recent evidence obtained with the angiotensin receptor blockers has allowed the recognition by most guidelines that this class of agents constitutes the first choice to treat hypertension in type 2 diabetic patients presenting with diabetic renal disease at any stage of evolution, from microalbuminuria to advanced renal failure. Of course this must be accompanied by an integral coverture of the increased global cardiovascular risk that always accompanies this situation. This short review contains the most relevant evidence in favour of angiotensin receptor blockers, with particular emphasis on the capacities of candesartan for controlling blood pressure and protecting the kidney. In patients with type 2 diabetes and varying degrees of albuminuria, treatment with candesartan 8-32mg daily was shown to reduce urinary albumin excretion (UAE) by up to 60%. When given in addition to an ACE inhibitor (dual blockade), reductions in UAE of 25 35% relative to ACE inhibitor monotherapy have been found. PMID- 17339066 TI - On switches and knobs, microsatellites and monogamy. AB - Comparative studies in voles have suggested that a polymorphic microsatellite upstream of the Avpr1a locus contributes to the evolution of monogamy. A recent study challenged this hypothesis by reporting that there is no relationship between microsatellite structure and monogamy in 21 vole species. Although the study demonstrates that the microsatellite is not a universal genetic switch that determines mating strategy, the findings do not preclude a substantial role for Avpr1a in regulating social behaviors associated with monogamy. PMID- 17339067 TI - Terrestrial carbon and intraspecific size-variation shape lake ecosystems. AB - Conceptual models of lake ecosystem structure and function have generally assumed that energy in pelagic systems is derived from in situ photosynthesis and that its use by higher trophic levels depends on the average properties of individuals in consumer populations. These views are challenged by evidence that allochthonous subsidies of organic carbon greatly influence energy mobilization and transfer and the trophic structure of pelagic food webs, and that size variation within consumer species has major ramifications for lake community dynamics and structure. These discoveries represent conceptual shifts that have yet to be integrated into current views on lake ecosystems. Here, we assess key aspects of energy mobilization and size-structured community dynamics, and show how these processes are intertwined in pelagic food webs. PMID- 17339069 TI - Evaluation of recombinant BCG expressing rotavirus VP6 as an anti-rotavirus vaccine. AB - Recombinant BCG expressing rotavirus VP6 was explored as an anti-rotavirus vaccine in a mouse model. Three promoters and five ribosome-binding sites were used in episomal and integrative E. coli-mycobacterium shuttle vectors to express VP6 in BCG. The VP6 gene was configured for accumulation within the BCG cytoplasm, secretion from the BCG cell or targeting to the BCG cell membrane. Vectors were assessed in terms of stability, levels of antigen production, immunogenicity and protection in mice. Gross instability occurred in episomal vectors utilizing the hsp60 promoter. However, three integrative vectors using the same expression system and two episomal vectors using inducible promoters were successfully recovered from BCG. Growth rates of the former were not detectably reduced. Growth rates of the latter were considerably reduced, implying the existence of a significant metabolic load. In the absence of selection, loss rate of these plasmids was high. VP6 production levels (0.04 1.78% of total cytoplasmic protein) were on the lower end of the range reported for other rBCG. One episomal and one integrated vaccine reduced viral shedding in intraperitoneally vaccinated mice challenged with rotavirus. Compared to controls, infection-associated faecal shedding of virus was reduced by 66% and 62%, respectively. These protective vectors differ in promoter, ribosome-binding site and antigen production level, but both link the VP6 protein to the 19kDa lipoprotein signal sequence, suggesting that transport of VP6 to the BCG membrane is important for induction of a protective immune response. Protection occurred in the absence of detectable anti-rotavirus antibody in serum or faeces, implicating cellular immunity in protection. PMID- 17339070 TI - Does increased gender equality lead to a convergence of health outcomes for men and women? A study of Swedish municipalities. AB - This study examines associations between indicators of gender equality and public health. We compare Swedish municipalities on nine indicators in both the private and public sphere, and an additive index, and study the correlations with indicators of morbidity and mortality. The hypothesis that a higher level of gender equality is associated with a convergence of health outcomes (life expectancy, sickness absence) between men and women was supported for equality of part-time employment, managerial positions and economic resources for morbidity, and for temporary parental leave for mortality. Our main finding is that gender equality was generally correlated with poorer health for both men and women. Our conclusions are tentative due to the methodological uncertainties. However, the results suggest an unfortunate trade-off between gender equality as we know it and public health. Sweden may have reached a critical point where further one sided expansion by women into traditionally male roles, spheres and activities will not lead to positive health effects unless men also significantly alter their behaviour. Negative effects of this unfinished equality might be found both for women, who have become more burdened, and men, who as a group have lost many of their old privileges. We propose that this contention be confronted and discussed by policymakers, researchers and others. Further studies are also needed to corroborate or dispute these findings. PMID- 17339071 TI - The role of oxidative stress in zearalenone-mediated toxicity in Hep G2 cells: oxidative DNA damage, gluthatione depletion and stress proteins induction. AB - Zearalenone (ZEN) is a fusarial mycotoxin with several adverse effects in laboratory and domestic animals including mainly estrogenicity. While most ZEN toxic effects have been quite well investigated, little is known regarding its mechanism of toxicity. Our previous investigations have shown the involvement of cytotoxicity, inhibition of macromolecules synthesis as well as genotoxicity. However, there are no available data regarding the involvement of the oxidative stress pathway in ZEN toxicity. In this context, the aim of this study was to find out whether ZEN induces oxidative cell damage. Using human hepatocytes Hep G2 cells, ZEN-induced stress response is monitored at several levels in these cells. ZEN mediated induction of oxidative DNA damage (comet assay using the repair enzymes), modulation of gluthatione (GSH), cytotoxicity (growth inhibition) and the oxidative stress responsive gene Hsp 70 and Hsp 90 were investigated with respect to concentration and time dependency. Hep G2 cells respond to ZEN exposure by loss of cell viability, induction of oxidative DNA damage, GSH depletion and Hsp 70 and Hsp 90 induction already at concentrations, which are not yet cytotoxic. The perturbation of the oxidative status was further confirmed by the significant reduction of the induced oxidative DNA damage as well as stress protein induction when cells were pre-treated with Vitamin E prior to exposure to ZEN. Our study clearly demonstrates that oxidative damage is likely to be evoked as one of the main pathway of ZEN toxicity. This oxidative damage may therefore be an initiating event and contribute, at least in part, to the mechanism of ZEN different genotoxic and cytotoxic effects. PMID- 17339072 TI - Effects of elevated hydrogen peroxide 'strip' bleaching on surface and subsurface enamel including subsurface histomorphology, micro-chemical composition and fluorescence changes. AB - OBJECTIVES: This study examined the effects of elevated concentration hydrogen peroxide tooth whitening treatments on tooth surface and subsurface integrity. METHODS: Sound human molars were ground and polished to prepare an uniform substrate for bleaching treatments. A cycling treatment included alternating ex vivo human salivary exposures with bleaching treatments under conditions of controlled temperature and durations of treatment. Bleaching was carried out with prototype bleaching strips containing hydrogen peroxide gel at 13% and 16% concentrations. A non-bleached group was used as a control. Treatments included 28h of total bleaching exposure in vitro. Surface color was measured prior to and following bleaching. Effects of bleach on physical properties of tooth surfaces were assessed by microhardness measures on enamel. Ultrastructural effects were examined by surface and subsurface confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) techniques. In addition, the effects of bleaching on tooth micro-chemical composition were studied by Raman spectroscopy combined with CLSM technique. RESULTS: Color assessments confirmed significant ex vivo tooth bleaching. Surface microhardness and VP-SEM (variable pressure SEM) measures revealed no deleterious effects on the enamel surfaces. CLSM micromorphological assessments supported the safety of hydrogen peroxide bleaching strips both on surface and subsurface enamel, DEJ and dentin ultrastructure. Raman spectroscopy analysis demonstrated no obvious effects of bleaching treatments on the micro-chemical composition of enamel and dentin. Significant effects of bleaching were seen in reducing background luminescence of Raman spectra obtained from enamel and dentin. CONCLUSIONS: These results confirm that hydrogen peroxide whitening strips do not produce changes in surface/subsurface histomorphology, surface microhardness and micro-chemical composition of teeth. Effects of bleaches on tooth luminescence recorded in micro Raman spectroscopy may serve as an internal signature to bleaching effects and warrant further study. PMID- 17339073 TI - Water stress, water transfer and social equity in Northern China--implications for policy reforms. AB - Water stress in Northern China is characterized with major, inefficient irrigation water use and rapidly growing non-agricultural water demands, as well as limited water quantity and declining water quality. Water use in the region is undergoing transfer from agricultural to municipal and industrial sectors. Currently, part of the economic loss and environmental damage due to water stress can be considered as a consequence of water transfer failures, including the current transfers, which hurt farmers' livelihood and income, and the needed transfers, which industry and cities have been waiting for but have not received. This paper starts with a discussion of the causes of water stress in Northern China, which is fundamental to understand the necessity and complexity of agricultural water transfers. Following that, it reviews water transfers in Northern China as a cause for concern over the social stability, economy and environment of the region. Based on an integrated analysis of economic, environmental, fiscal and social implications, this paper begins by identifying critical barriers to smooth water redistribution; and ends with implications for policy reforms, ensuring that farmers can and will save water. It is concluded that the decisions of water reallocation under water stress should be shared by communities at all levels, from the local to the national, to ensure equal access of water, especially the availability of the basic water need for all groups. PMID- 17339074 TI - The extent of lymph node dissection in patients with localised prostate cancer: debate continues. PMID- 17339075 TI - Proceedings of the 1st International Symposium on Gonadal and Nongonadal Actions of LH/hCG, June 3-4, 2005, Turku, Finland. PMID- 17339076 TI - Transition state kinetics of Hg(II) adsorption at gibbsite-water interface. AB - Kinetics of adsorption plays a pivotal factor in determining the bio-availability and mobility of Hg(II) in the environment. The kinetics of Hg(II) adsorption on gibbsite was examined as a function of pH, temperature and electrolyte type. Adsorption of Hg(II) was highly non-linear where the rate of Hg(II) retention was rapid initially and was followed by gradual or somewhat slow retention behavior with increasing contact time. The respective rate constants designated as k(1) (S 1: fast step) and k(2) (S-2: slow step). Always k(1) follows the order: k(1)(CIO)(4) >/= k(1)(NO3)(4) >> k(1)(Cl). Such a relationship was not observed for the S-2 route. A two-step reaction model with pseudo-first order kinetics successfully described the adsorption rates of Hg(II) on gibbsite. Arrhenius and Erying models determined the thermodynamic parameters at activation states, which correspond to S-1 and S-2 routes. In a given system, always the activation energies showed a decrease with the pH. Gibbs free energy (DeltaG(#)), enthalpy (DeltaH(#)), and entropy (DeltaS(#)) values of activation states were almost similar both in NaClO(4) and NaNO(3) which signal a similar Hg(II) adsorptive mechanism on gibbsite. The configurations of different Hg(II)-surface complexes were elucidated by transmission vibration spectroscopy. PMID- 17339077 TI - Gaseous emissions from waste combustion. AB - An overview is given on methods and technologies for limiting the gaseous emissions from waste combustion. With the guideline 2000/76/EC recent European legislation has set stringent limits not only for the mono-combustion of waste in specialized incineration plants but also for co-combustion in coal-fired power plants. With increased awareness of environmental issues and stepwise decrease of emission limits and inclusion of more and more substances into the network of regulations a multitude of emission abatement methods and technologies have been developed over the last decades. The result is the state-of-the-art waste incinerator with a number of specialized process steps for the individual components in the flue gas. The present work highlights some new developments which can be summarized under the common goal of reducing the costs of flue gas treatment by applying systems which combine the treatment of several noxious substances in one reactor or by taking new, simpler routes instead of the previously used complicated ones or - in the case of flue gas desulphurisation - by reducing the amount of limestone consumption. Cost reduction is also the driving force for new processes of conditioning of nonhomogenous waste before combustion. Pyrolysis or gasification is used for chemical conditioning whereas physical conditioning means comminution, classification and sorting processes. Conditioning yields a fuel which can be used in power plants either as a co-fuel or a mono-fuel and which will burn there under much better controlled conditions and therefore with less emissions than the nonhomogeneous waste in a conventional waste incinerator. Also for cost reasons, co-combustion of wastes in coal-fired power stations is strongly pressing into the market. Recent investigations reveal that the co-firing of waste can also have beneficial effects on the operating behavior of the boiler and on the gaseous emissions. PMID- 17339078 TI - Removal of chromium ions from aqueous solutions by polymer-enhanced ultrafiltration. AB - This study deals with the removal of chromium species from aqueous dilute solutions using polymer-enhanced ultrafiltration (PEUF) process. Three water soluble polymers, namely chitosan, polyethyleneimine (PEI) and pectin were selected for this study. The ultrafiltration studies were carried out using a laboratory scale ultrafiltration system equipped with 500,000 MWCO polysulfone hollow fiber membrane. The effects of pH and polymer composition on rejection coefficient and permeate flux at constant pressure have been investigated. For Cr(III), high rejections approaching 100% were obtained at pH higher than 7 for the three tested polymers. With chitosan and pectin, Cr(VI) retention showed a slight increase with solution pH and did not exceed a value of 50%. An interesting result was obtained with PEI. The retention of Cr(VI) approached 100% at low pH and decreased when the pH was increased. This behavior is opposite to what one can expect in the polymer-enhanced ultrafiltration of heavy metals. Furthermore, the concentration of polymer was found to have little effect on rejection. Permeate flux remained almost constant around 25% of pure water flux. PMID- 17339079 TI - Decreased vesicular acetylcholine transporter and alpha(4)beta(2) nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning. AB - Degeneration of cholinergic neurons is a well known characteristic of Alzheimer's disease (AD). Two radioligands were studied in a rat model of cholinergic degeneration to evaluate their potential efficacy for molecular imaging of AD. Following specific cholinergic-cell immunolesioning with 192 IgG-saporin (SAP), ex vivo autoradiography was performed with (123)IBVM, a radioligand which targets the vesicular acetylcholine transporter (VAChT). Following the decay of (123)I, the same animals had in vitro autoradiography performed with (125)I-A-85380, a marker for nicotinic acetylcholine receptors (nAChRs). As expected significant, widespread decreases in (123)IBVM uptake were observed in SAP treated animals. Moderate but significant reductions in (125)I-A-85380 binding in the hippocampus (Hip) and cerebellum (Cbm) were also observed following SAP immunolesioning. The results with (123)IBVM confirm and extend previous work investigating the uptake of radioiodinated IBVM in this animal model. The results with (125)I-A-85380 are unique and are in contrast with work performed in this animal model with other nAChR radioligands, indicating the favourable properties of this radioligand for molecular imaging. PMID- 17339080 TI - Increased accumbens Cdk5 expression in rats after short-access to self administered cocaine, but not after long-access sessions. AB - Upregulation of cyclin-dependent kinase 5 (Cdk5) after chronic cocaine administration has led to speculation that Cdk5 plays an important role in drug addiction. However, as Cdk5 involvement is implicated in a variety of neural events, including neuronal development, synaptic plasticity and learning, a specific role in drug abuse is yet to be determined. The present study utilized cocaine self-administration and food-reinforced operant procedures to assess possible relationships between cocaine intake, food-reinforced operant responding, behavioral activity, and Cdk5 levels in the nucleus accumbens (NAcc), ventral tegmental area (VTA), and prefrontal cortex (PFC) in rats. In Experiment 1, animals undergoing daily cocaine self-administration (1-h/30 days) or food reinforced operant sessions (20-min/30 days) showed significant between-group differences in operant responding and behavioral activity, but no significant differences in NAcc, VTA or PFC Cdk5 levels compared to a Handled Control group. In Experiment 2, animals that had self-administered cocaine in 10 daily 1-h sessions (Short-Access Cocaine) showed significantly greater NAcc Cdk5 expression compared to an Unhandled Control group, and no evidence of cocaine-induced behavioral sensitization. Animals given 4-h daily access to cocaine over the same number of sessions (Long-Access Cocaine) showed significantly enhanced cocaine reinforced responding and locomotor activation by the end of the sessions, but no significant differences in Cdk5 expression compared to Control animals. These findings suggest that overexpression of Cdk5 may be a transient adaptation to cocaine experience that subsides with increased cocaine exposure and does not correspond with measures of cocaine-induced behavioral sensitization. PMID- 17339081 TI - Inhibitory action of protein kinase Cbeta inhibitor on tetrodotoxin-resistant Na+ current in small dorsal root ganglion neurons in diabetic rats. AB - Experimental evidence has been presented to suggest that protein kinase Cbeta isoform-selective inhibitor LY333531 is effective at alleviating diabetic hyperalgesia. In the present study, we isolated small (< or =25 microm in soma diameter) dorsal root ganglion (DRG) neurons from control and streptozocin (STZ) induced diabetic rats, and examined the acute action of LY333531 (1-1000 nM) on the tetrodotoxin-resistant Na(+) current (TTX-R I(Na)), which plays an essential role in transmitting nociceptive impulses, using the whole-cell patch-clamp method. TTX-R I(Na) in diabetic DRG neurons was enhanced in amplitude (71.5+/ 3.6pA/pF, n=10 versus 41.2+/-3.3pA/pF, n=8) and was activated at more negative potentials (V(1/2), -15.1+/-1.3 mV versus -9.6+/-1.4 mV), compared with that in control neurons. Bath application of LY333531 acutely inhibited TTX-R I(Na) in both control and diabetic DRG neurons, and the degree of inhibition by the drug at concentrations of 1, 10 and 100 nM was significantly greater in diabetic DRG neurons than in control DRG neurons. Thus, TTX-R I(Na), which is upregulated in the diabetic state, is likely to be more potently inhibited by submicromolar concentrations of LY333531. These results suggest that an acute inhibition of TTX R I(Na) by LY333531 attenuates the exaggerated excitability of DRG neurons in the diabetic state, which appears to be related at least partly to anti-hyperalgesic actions of the drug in diabetic neuropathy. PMID- 17339083 TI - Does a mutated X-linked dominant transcriptional repressor gene explain mirror writing ability and synaesthesia? AB - X-linked dominant conditions tend to present as two distinct sex-dependent phenotypes. Mirror writing ability and synaesthesia both appear to fall into this category. The existence of two different phenotypes in these two conditions is advanced as a reason associated with regarding their genetic mode of transmission as being X-linked dominant. The alternative autosomal mode cannot account for different male and female phenotypes. It is suggested that the gene for mirror writing ability, a trait linked to non-right-handedness, negates the normal process of left-lateralisation of language. Similarities between mirror writing ability and synaesthesia are documented and it is further suggested that these similarities can be explained if the genes for each condition are regarded as target genes for the same mutated X-linked dominant transcriptional repressor gene, possibly MeCP2. PMID- 17339084 TI - Colorectal cancer screening: its time for action in Asia. PMID- 17339085 TI - ELISA and PCR for evaluation of subclinical paratuberculosis in the Saudi dairy herds. PMID- 17339087 TI - Autosomal microsatellite allele frequencies for a nationwide dataset from the Australian Caucasian sub-population. AB - DNA profiling results presented in court must be accompanied by a statistical estimate of its evidential weight. In calculating such statistics, allele frequencies from the tested loci are required. This paper reports allele frequencies and the results of population genetic testing of datasets of autosomal microsatellite profiles from Australian Caucasian donors. In contrast to previous practice in Australia these data have been collated at the national level rather than at the State and Territory level. We consider that this national dataset could be used in forensic DNA casework throughout Australia as previously recommended by Ayres et al. [K.L. Ayres, J. Chaseling, D.J. Balding, Implications for DNA identification arising from an analysis of Australian forensic databases, Forensic Sci. Int. 129 (2002) 90-98]. PMID- 17339086 TI - The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons. AB - Local direct application of the neuromodulator serotonin strongly influences auditory response properties of neurons in the inferior colliculus (IC), but endogenous stores of serotonin may be released in a distinct spatial or temporal pattern. To explore this issue, the serotonin releaser fenfluramine was iontophoretically applied to extracellularly recorded neurons in the IC of the Mexican free-tailed bat (Tadarida brasiliensis). Fenfluramine mimicked the effects of serotonin on spike count and first spike latency in most neurons, and its effects could be blocked by co-application of serotonin receptor antagonists, consistent with fenfluramine-evoked serotonin release. Responses to fenfluramine did not vary during single applications or across multiple applications, suggesting that fenfluramine did not deplete serotonin stores. A predicted gradient in the effects of fenfluramine with serotonin fiber density was not observed, but neurons with fenfluramine-evoked increases in latency occurred at relatively greater recording depths compared to other neurons with similar characteristic frequencies. These findings support the conclusion that there may be spatial differences in the effects of exogenous and endogenous sources of serotonin, but that other factors such as the identities and locations of serotonin receptors are also likely to play a role in determining the dynamics of serotonergic effects. PMID- 17339088 TI - Evidence against the involvement of nitric oxide in the modulation of telomerase activity or replicative capacity of human endothelial cells. AB - Telomerase, a reverse transcriptase involved in the maintenance of telomere function and cellular replicative capacity, is thought to be regulated by nitric oxide (NO). Here, we have used pharmacological tools and RNA interference to re assess the role of NO in the regulation of telomerase and senescence of human umbilical vein endothelial cells. Acute or chronic treatment of these cells with the NO donors diethylenetriamine/NO (DETA-NO) or S-nitroso-N-acetylpenicillamine (SNAP) at concentrations which generated NO in the 1-300 nM range did not modulate telomerase activity. Similarly these agents did not affect cellular replicative capacity during long-term sub-cultivation. The NO synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (1 mM) reduced basal levels of c-GMP by 50% but had no effect on telomerase activity or replicative capacity. Withdrawal of ascorbic acid increased the intracellular pro-oxidant capacity, reduced telomerase activity and increased the accumulation of senescent cells upon serial passage in culture. However, this shift to a more oxidative redox state did not unmask the putative capacity of NO to modulate telomerase or senescence. Infection of cells with a lentiviral vector expressing a small hairpin RNA targeted against endothelial NOS inhibited endogenous NO production completely but failed to affect the decrease of telomerase activity or the accumulation of senescent cells observed with passage in culture. Our findings suggest that physiological concentrations of NO do not modulate telomerase levels or replicative capacity of endothelial cells, regardless of their cellular oxidative status. PMID- 17339089 TI - Functional MRI approach for assessing hemispheric predominance of regions activated by a phonological and a semantic task. AB - This fMRI study performed in healthy subjects aimed at using a statistical approach in order to determine significant functional differences between hemispheres and to assess specialized regions activated during a phonological and during a semantic task. This approach ("flip" method and subsequent statistical analyses of the parameter estimates extracted from regions of interest) allows identifying: (a) hemispheric specialized regions for each language task [semantic (living categorization) and phonological (rhyme detection)] and (b) condition specific regions with respect to paradigm conditions (task and control). Our results showed that the rhyme-specific task regions were the inferior frontal (sub-region of BA 44, 45) and left inferior parietal (BA 40, 39) lobules. Furthermore, within the inferior parietal lobule, the angular gyrus was specific to target (rhyming) items (related to successfully grapho-phonemic processing). The categorization-specific task regions were the left inferior frontal (sub region of BA 44, 45) and superior temporal (BA 22) cortices. Furthermore, the superior temporal gyrus was related to non-target (non-living) items (correlated to task difficulty). The relatively new approach used in this study has the advantage of providing: (a) statistical significance of the hemispheric specialized regions for a given language task and (b) supplementary information in terms of paradigm condition-specificity of the activated regions. The results (standard hemispheric specialized regions for a semantic and for a phonological task) obtained in healthy subjects may constitute a basement for mapping language and assessing hemispheric predominance in epileptic patients before surgery and avoiding post-surgical impairments of language. PMID- 17339090 TI - A novel parameter by EFOV US for the quantification and the distinction of physiological amount of scrotal fluid and hydrocele: ratio of testis volume/scrotum volume. AB - OBJECTIVE: To determine the limits for the amount of tunical fluid enough to be termed as hydrocele by using extended-field of view US technology and to define hydrocele for the first time with standard numerical criteria. METHODS: A total of 60 patients were evaluated in this prospective study. Group 1 consisted of 20 patients with unilateral clinical hydrocele. Group 2 included 20 patients referred for scrotal US for reasons other than hydrocele. Group 3 comprised 20 male controls with no scrotal complaints. Testis volume (V(t)), scrotum volume (V(s)) and V(t)/V(s) ratio were calculated for each subject by dimensions measured in longitudinal and tranverse planes. RESULTS: Mean V(t)/V(s) ratio was 0.28 +/- 0.17 (range, 0.07-0.57), 0.69 +/- 0.08 (range, 0.53-0.80) and 0.71 +/- 0.07 (range, 0.61-0.85) for groups 1, 2 and 3, respectively. Mean V(t)/V(s) for group 1 was significantly lower than those for groups 2 and 3, respectively (p<0.001 for each). Based on the ROC curve analysis, 0.55 for V(t)/V(s) ratio was determined as the optimal cut-off point below which the US diagnosis of hydrocele could be made (sensitivity 95.0% and specificity 97.5%). CONCLUSIONS: We propose a novel US parameter of V(t)/V(s) ratio below 0.55 for a standard distinction between hydrocele and physiological amount of scrotal fluid. PMID- 17339091 TI - Application of LC-MS for quantitative analysis and metabolite identification of therapeutic oligonucleotides. AB - Therapeutic oligonucleotides (OGNs) have been studied extensively in the recent years as novel agents designed to selectively and specifically inhibit target gene expression in cell culture, in animal disease models and in human. This review summarizes applications of liquid chromatography coupled with mass spectrometry or tandem mass spectrometry (LC-MS or LC-MS/MS) for quantitative analysis of therapeutic OGNs and characterization of their metabolism in vitro and in vivo described in the literature over the past 10 years. Although the applications of LC-MS or LC-MS/MS to the molecular mass measurement, sequence determination, DNA adducts identification, detection of mutations and characterization of covalent and/or noncovalent DNA/RNA complexes have been comprehensively reviewed in a few excellent review papers. The quantitative bioanalysis and metabolite identification of therapeutic OGNs using LC-MS or LC MS/MS have not been covered. This review covers technical issues, current approaches and applications of LC-MS or LC-MS/MS for quantitative analysis of OGNs in biological matrices and characterization of their in vitro and in vivo metabolism. Finally, some conclusions are drawn and prospects of LC-MS in quantitative analysis and metabolism characterization of therapeutic OGNs are discussed. PMID- 17339092 TI - A trip to the nursing home. PMID- 17339093 TI - Does training general practitioners to elicit patients' illness representations and action plans influence their communication as a whole? AB - OBJECTIVE: To examine whether the discussion of illness representations and action plans during medical encounters affects the way patients and general practitioners (GPs) communicate. METHODS: In a quasi-experimental design, 10 GPs first performed care-as-usual conversations with patients. After a 6 h training they performed consultations either emphasizing patients' illness representations or action plans. Data were collected from 70 videotaped consultations with hypertensive patients, which were analyzed using the Roter Interaction Analysis System. RESULTS: Compared with care-as-usual consultations, communication in the action plan condition resulted in an increased discussion of lifestyle issues whereas communication in the illness representation condition resulted in more discussion of patient concerns. In both experimental conditions the proportion of affective GP utterances was higher while patients contributed more to the conversation. When GPs changed their communication style, patients did accordingly. CONCLUSION: The explicit address of illness representations or action plans during consultations results in more attention to patient concerns and lifestyle issues and an overall improvement in patient-GP communication in terms of affective atmosphere and patient involvement. PRACTICE IMPLICATIONS: These findings show that after a brief training GPs are able to change their communication style in a way that allows for a more thorough consideration of patient self-management. PMID- 17339094 TI - Performance on a neurocognitive measure of alerting differentiates ADHD combined and inattentive subtypes: a preliminary report. AB - The performance of 16 attention-deficit hyperactivity disorder (ADHD)/C, 26 ADHD/IA, and 24 control children was compared using a computer reaction time task designed to measure the effects of Posner's orienting, conflict and alerting attentional systems. No group differences in orienting or conflict were found. In contrast, children with ADHD/IA showed stronger alerting effects than those with ADHD/C, as indicated by relatively greater performance benefits following a warning cue. Although neither ADHD group differed significantly from controls on alerting, effect size comparisons indicated that children with ADHD/IA showed a somewhat larger (d=.57) and children with ADHD/C a somewhat smaller (d=.44) alerting effect relative to control children. The results are among the first to document unique patterns of attentional capacity for ADHD subtypes. PMID- 17339095 TI - Psychometric properties of the School Anxiety Scale-Teacher Report (SAS-TR). AB - This paper describes the development and psychometric evaluation of a teacher report scale of anxiety in children. After initial pilot, the School Anxiety Scale-Teacher Report (SAS-TR) was reduced to 16 items which were answered on a 4 point scale. Psychometric evaluation was conducted on 240 community and 140 anxiety disordered children aged 5-12 years. Factor analysis identified two subscales reflecting social and generalized anxiety. The SAS-TR was found to have acceptable internal consistency, appropriate relationships with other teacher report scales, and was positively correlated with parent report of child anxiety. Gender and age effects on total and subscale scores were not evident. Clinical utility was evident with the scale discriminating between the community and clinical groups, correctly classifying a large proportion of anxiety disordered children and showing sensitivity to changes in anxiety with treatment. The SAS-TR complements existing measures and can be used within a multi-informant approach to the assessment of child anxiety. PMID- 17339097 TI - Changes in social fears across childhood and adolescence: age-related differences in the factor structure of the Fear Survey Schedule for Children-Revised. AB - The (in)variance of the structure of fear across child and adolescent development was investigated using the response of 3,803 young people (aged 6-18 years) to the Fear Survey Schedule for Children-Revised (FSSC-R). It was hypothesized that the structure of fear, particularly social fear, would become more differentiated during adolescence. Confirmatory factor analysis was utilized to test the goodness-of-fit of a 5-factor solution (with one social factor, that is Failure and Criticism) and a 7-factor solution (with social items divided into three distinct subfactors) among three age groups. Results indicated that a 5-factor solution (including just one social factor) adequately characterizes the structure of fear in childhood (6-9 years), whereas a 7-factor solution (including three social factors) more appropriately characterizes the structure of fear in adolescence (10-13 and 14-18 years). It appears that a global social fear exists until around the age of 9, and that social fears becomes more differentiated thereafter. PMID- 17339096 TI - Characterizing the hoarding phenotype in individuals with OCD: associations with comorbidity, severity and gender. AB - Hoarding frequently occurs in obsessive-compulsive disorder (OCD), and some evidence suggests that it constitutes a distinct OCD subtype, with genetic contributions. This study investigated differences between OCD patients with and without hoarding symptoms. Of the 473 OCD patients studied, 24% were classified as hoarders according to combined interviewer and self-ratings, which were validated with the Savings Inventory-Revised in a subsample. Hoarders suffered from significantly more severe OCD symptoms, (especially compulsions) and had greater impairment and dysphoria. Hoarders also had more comorbid psychiatric disorders. Further study revealed that many of these differences were attributable to the female subjects: Compared to female non-hoarders, female hoarders were more likely to suffer from bipolar I, substance abuse, panic disorder, binge-eating disorder, and had greater OCD severity. Male hoarders had an increased prevalence of social phobia compared to non-hoarding males. These results suggest that there are gender-specific differences in the hoarding sub phenotype of OCD. PMID- 17339098 TI - Alleviation of the effects of endotoxin exposure on behavior and hippocampal IL 1beta by a selective non-peptide antagonist of corticotropin-releasing factor receptors. AB - Previous research has shown that lipopolysaccharide (LPS) or interleukin-1beta (IL-1beta) administration produces learning/memory deficits in a variety of paradigms. In our laboratory, we have consistently observed LPS-induced behavioral alterations in a two-way active avoidance conditioning paradigm. Following LPS administration, one factor that affects cytokine production is corticotropin-releasing factor (CRF). CRF has well known anti-inflammatory effects, via stimulation of ACTH and corticosterone release. However, CRF acting directly on immune cells or within the CNS may potentiate proinflammatory effects. The current experiments explored the potential of antalarmin, a CRF-R1 non-peptide antagonist, to diminish or negate deficits observed with LPS administration. On the first day of testing, four-month-old male C57BL/6J mice received an intraperitoneal (i.p.) injection of antalarmin, followed 90min later by a second i.p. injection of LPS 4h prior to two-way active avoidance conditioning testing. As hypothesized, LPS administration altered performance. However, pretreatment with antalarmin attenuated the adverse effects of LPS administration. Moreover, evidence indicates that antalarmin attenuated hippocampal, but not peripheral, cytokine release. The behavioral results cannot be explained by alterations in the HPA axis, as antalarmin did not affect the LPS induced rise in corticosterone. The current research contributes preliminary evidence that CRF may be an important factor in the development of LPS-induced behavioral effects, and that blocking the activity of CRF may be sufficient to alleviate some of the effects of endotoxin exposure, possibly due to diminished LPS-induced IL-1beta release in the dorsal hippocampus. PMID- 17339099 TI - Carotid artery resection and reconstruction: clinical experience of 28 consecutive cases. AB - The aim of this study was to analyse the experience at a single institution in carotid artery resection with or without reconstruction performed as part of an oncological procedure or emergency haemostasis. A total of 28 patients were included in this retrospective study; 17 underwent ligation or resection of the carotid artery, and 11 underwent reconstruction of the carotid artery. The perioperative complications and surgical outcomes were recorded and analysed. Of the 17 patients with ligation or resection of the carotid artery, 4 developed neurologic deficit within 2 weeks postoperatively. Three patients with malignant tumours died 1 month (1) and 4 months (2) postoperatively. Of the 11 patients undergoing carotid reconstruction, no major cerebral complications were noted after operation. Colour Doppler showed patent vascular graft 1 year postoperatively in nine patients. Due to the higher complication rates both in short and long term with ligation or resection of the carotid artery, resection and revascularization of the carotid artery is advocated for patients with carotid artery involvement when possible. PMID- 17339100 TI - Primary oral KIT-positive tumour consistent with gastrointestinal stromal tumour. AB - Gastrointestinal stromal tumours are characteristically positive for KIT (reflective of the c-KIT gene). A case is reported of an apparent rapidly growing gastrointestinal stromal tumour, which arose in the floor of the mouth and metastasized to the left neck without evidence of disease elsewhere. PMID- 17339101 TI - Quality of life in patients with dentofacial deformity: a comparison of measurement approaches. AB - The aim of this study was to examine the effect of dentofacial deformity on quality of life (QOL) as assessed by generic health, generic oral health and condition-specific approaches. A case-control study was performed involving 154 subjects: 76 with dentofacial deformity (non-cleft) and 76 without dentofacial deformity. Generic health-related QOL was assessed employing the 36-item Short Form Health Survey (SF-36), generic oral health-related QOL was assessed by the 14-item short form Oral Health Impact Profile (OHIP-14) and condition-specific QOL was assessed by the 22-item Orthognathic Quality of Life Questionnaire (OQLQ). No significant difference in SF-36 scores between case and control groups was observed (P>0.05). There were significant differences in overall OHIP-14 scores (P<0.001) and overall OQLQ scores (P<0.001) between case and control groups. The results suggest that dentofacial deformity affects individuals in many aspects of their lives, and that generic oral health and condition-specific approaches to assessing QOL are able to discriminate patients with dentofacial deformities from those without, and thus have value in determining the impact of dentofacial deformities on QOL. PMID- 17339102 TI - Novel molecular targets for antimalarial chemotherapy. AB - The emergence and spread of drug-resistant malaria parasites is a serious public health problem in the tropical world. Malaria control has relied upon the traditional quinoline, antifolate and artemisinin compounds. Very few new antimalarials were developed in the last quarter of the 20th century. An alarming increase in drug-resistant strains of the malaria parasite poses a significant problem for effective control. Recent advances in our knowledge of parasite biology as well as the availability of the genome sequence provide a wide range of novel targets for drug design. Gene products involved in controlling vital aspects of parasite metabolism and organelle function could be attractive targets. It is expected that the application of functional genomic tools in combination with modern approaches such as structure-based drug design and combinatorial chemistry will lead to the development of effective new drugs against drug-resistant malaria strains. This review discusses novel molecular targets of the malaria parasite available to the drug discovery scientist. PMID- 17339103 TI - Intracellular distribution of fluorescent probes delivered by vesicles of different lipidic composition. AB - In order to study mechanisms involved in liposome-cell interaction, this work attempted to assess the influence of vesicle composition on the delivery of liposomal content to Hela cells. In particular, to evaluate pH-sensitive properties and cell interaction of the prepared liposomes, the lipid formulations contained cholesterol (Chol) and they were varied by using phosphatidylcholines with different purity degree: soy lecithin (SL; 80% phosphatidylcholine), a commercial mixture of soy phosphatidylcholine (P90; 90% phosphatidylcholine) or dipalmitoylphosphatidylcholine (DPPC; 99% of purity). A second series of liposomes also contained stearylamine (SA). Dehydration-rehydration vesicles (DRV) were prepared and then sonicated to decrease vesicle size. Vesicle-cell interactions and liposomal uptake were examined by fluorescence microscopy using carboxyfluorescein (CF) and phosphatidylethanolamine-dioleoyl-sulforhodamine B (Rho-PE) as fluorescent markers. Fluorescence dequenching assay was used to study the influence of pH on CF release from the liposomal formulations. Liposome adhesion on the cell surface and internalization were strongly dependent on vesicle bilayer composition. SA vesicles were not endocytosed. DPPC/Chol liposomes were endocytosed but did not release their fluorescent content into the cytosol. SL/Chol and P90/Chol formulations displayed a diffuse cytoplasmic fluorescence of liposomal marker. PMID- 17339104 TI - Fatty alcohols or fatty acids as niosomal hybrid carrier: effect on vesicle size, encapsulation efficiency and in vitro dye release. AB - Niosomal hybrid mixtures are prepared with bilayer stabilizer cholesterol from non-ionic surfactants span 20 (HLB value 8.6), span 60 (HLB 4.7) and span 85 (HLB 1.8) in presence of dicetyl phosphate (DCP) where fatty acids or fatty alcohols (C14, C16 and C18) are used as carrier. Hybrid mixtures upon hydration with aqueous phosphate buffer (pH 7.4) spontaneously produce vesicular phase which can encapsulate 5(6)-carboxyfluorescein (CF). Effect of fatty alcohols and fatty acids on the vesicle size has been studied by dynamic light scattering (DLS), freeze-fracture scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Release rates of CF from vesicular suspensions are found to be dependent on carriers as well as surfactants used. Fatty acid coated hybrids form large multilamellar vesicles (LMV) (size range 10-15 microm) where as fatty alcohol coated hybrid systems form small multilamellar vesicles (SMV) with an average diameter of 400 nm, in all cases vesicles are polydisperse (PI approximately 0.9) in nature. PMID- 17339105 TI - Structural characterization of insulin NPH formulations. AB - Insulin NPH (neutral protamine hagedorn) has for long been one of the most important therapeutic formulations for the treatment of diabetes. The protracted action profile of NPH formulations is gained from crystallizing insulin with zinc in the presence of the basic poly-arginine peptide protamine. In spite of its long history and successful use, the binding mode of the insulin-protamine complex is not known. In this study, three different systems were used to study protamine binding to insulin. In the first system, crystals of an insulin protamine complex grown in the presence of urea and diffracting to 1.5A resolution were analyzed. In the second system, a shorter peptide consisting of 12 arginine residues was co-crystallized with insulin in order to reduce the flexibility and thereby improve the electron density of the peptide. Both systems yielded data to a significantly higher resolution than obtained previously. In addition, a third system was analyzed where crystals of insulin and protamine were grown in the absence of urea, with conditions closely resembling the pharmaceutical formulation. Data from these NPH microcrystals could for the first time be collected to 2.2A resolution at a micro focused X-ray beamline. Analysis of all three crystal forms reveal potential protamine density located close to the solvent channel leading to the centrally located zinc atoms in the insulin hexamer and support that protamine binds to insulin in a not well defined conformation. PMID- 17339106 TI - Effects of an integrated care intervention on risk factors of COPD readmission. AB - An integrated care intervention including education, coordination among levels of care, and improved accessibility, reduced hospital readmissions in chronic obstructive pulmonary disease (COPD) after 1 year. This study analyses the effectiveness of this intervention in terms of clinical and functional status, quality of life, lifestyle, and self-management, under the hypothesis that changes in these factors could explain the observed reduction in readmissions. A total of 113 exacerbated COPD patients (14% female, mean (SD) age 73(8) years, FEV(1) 1.2(0.5) l) were recruited after hospital discharge in Barcelona, Spain, and randomly assigned (1:2) to integrated care (IC) (n=44) or usual care (UC) (n=69). The intervention consisted of an individually tailored care plan at discharge shared with the primary care team and access to a specialized case manager nurse through a web-based call centre. After 1 year of intervention, subjects in the intervention group improved body mass index by 1.34 kg/m(2). Additionally, they scored better in self-management items: COPD knowledge 81% vs. 44%, exacerbation identification 85% vs. 22%, exacerbation early treatment 90% vs. 66%, inhaler adherence 71 vs. 37%, and inhaler correctness 86 vs. 24%. There were no differences in the evolution of dyspnea, lung function, quality of life scores, lifestyle factors, or medical treatment. CONCLUSIONS: This IC trial improved disease knowledge, and treatment adherence, after 1 year of intervention, suggesting that these factors may play a role in the prevention of severe COPD exacerbations triggering hospital admissions. PMID- 17339107 TI - Predicting and evaluating response to omalizumab in patients with severe allergic asthma. AB - BACKGROUND: Omalizumab is a monoclonal antibody indicated for treatment of severe persistent allergic asthma inadequately controlled despite optimal controller therapy. We investigated whether patient selection could be targeted further. METHODS: Data from seven randomized controlled omalizumab trials were analyzed to investigate whether pre-treatment patient baseline clinical characteristics could be identified that were predictive of a superior response to omalizumab. We also studied whether patients who respond to omalizumab following a course of treatment could be reliably identified. Univariate/multivariate analyses of INNOVATE data were performed to identify predictive baseline measures and further investigated in efficacy analyses of pooled data from seven studies. The best method of identifying responders to omalizumab following treatment was determined by assessing the ability of various clinical response criteria to identify responders and discriminate patient exacerbation and other outcomes. RESULTS: Baseline total immunoglobulin E (IgE) was the only predictor of efficacy in INNOVATE. However, pooled analysis showed treatment benefits irrespective of IgE levels. In omalizumab-treated patients, physician's overall assessment following a course of treatment identified 61% as responders and best discriminated treatment outcomes. CONCLUSION: Baseline characteristics do not reliably predict benefit with omalizumab. Physician's overall assessment after 16 weeks of treatment is the most meaningful measure of response to therapy. PMID- 17339108 TI - Construction of marker-free transplastomic plants. AB - Because of its prokaryotic-type gene expression machinery, maternal inheritance and the opportunity to express proteins at a high level, the plastid genome (plastome or ptDNA) is an increasingly popular target for engineering. The ptDNA is present as up to 10,000 copies per cell, making selection for marker genes essential to obtain plants with uniformly transformed ptDNA. However, the marker gene is no longer desirable when homoplastomic plants are obtained. Marker-free transplastomic plants can now be obtained with four recently developed protocols: homology-based excision via directly repeated sequences, excision by phage site specific recombinanses, transient cointegration of the marker gene, and the cotransformation-segregation approach. Marker excision technology will benefit applications in agriculture and in molecular farming. PMID- 17339109 TI - Synthesis and biological evaluation of pyrido[3',2':4,5]furo[3,2-d]pyrimidine derivatives as novel PI3 kinase p110alpha inhibitors. AB - 4-Morpholin-4-ylpyrido[3',2':4,5]thieno[3,2-d]pyrimidine 2a was discovered in our chemical library as a novel p110alpha inhibitor with an IC(50) of 1.4 microM. By structural modification of 2a, the 2-aryl-4-morpholinopyrido[3',2':4,5]furo[3,2 d]pyrimidine derivative 10e was discovered as a p110alpha inhibitor with approximately 400-fold greater potency than 2a. Evaluation of isoform selectivity showed that 10e is a potent inhibitor of p110beta. Furthermore, 10e showed anti proliferative activity in various cell lines, including multi-drug resistant MCF7/ADR-res cells, and was effective against HeLa human cervical tumor xenografts in nude mice. PMID- 17339110 TI - Backache in a Duchenne boy. PMID- 17339111 TI - National Library for Health Emergency Care Specialist Library. PMID- 17339112 TI - In vitro efficiency of new acridyl derivatives against Plasmodium falciparum. AB - A series of new 9-substituted acridyl derivatives were synthesized and their in vitro antimalarial activity was evaluated against one chloroquine-sensitive strain (3D7) and three chloroquine-resistant strains [W2 (Indochina), Bre1 (Brazil) and FCR3 (Gambia)] of Plasmodium falciparum. Some compounds inhibit the growth of malarial parasite with IC50 or=30 mmHg across right ventricular outflow tract. Kaplan-Meier method was used to estimate time-related events. RESULTS: Subaortic stenosis was resected in 25 patients, 20 of whom (80%: 20/25) were discharged from hospital free from RVOTO. There was one early death: 2.9% mortality. Three patients died late. Actuarial survival was 85.1%+/-7.0% from 54 month onwards. Eleven survivors (36.7%: 11/30) experienced postoperative RVOTO. Obstruction was seen in 82% (9/11) of cases at subvalvular and/or valvular level. Surgery (n=4) or percutaneous intervention (n=2) was required in six patients. Patients discharged from hospital with RVOTO (n=8) were more likely to undergo reintervention for RVOTO (p=0.026). Freedom from reintervention for RVOTO decreased rapidly in the first two years to 86.5+/-6.3%, slowly thereafter (80.4+/-8.4% at year 7) and stabilized at 70.3+/-11.9% from year 11 on. Risk for RVOTO occurrence was 23.5+/-7.3% early after repair and progressively increased to level out at 53.6+/-11% at year 11. Patients who underwent subaortic resection were more likely (p=0.023) to be free from RVOTO occurrence or development. In the period under review, for patients who underwent ASO for simple (n=355) and complex (n=92) TGA, reoperation rate for neopulmonary stenosis was 0.3% (1/355) and 5.4% (5/92), respectively, to be compared to 11.8% (4/34) RVOTO rate of reoperation for Taussig-Bing heart in this study. CONCLUSIONS: Postoperative right-sided obstruction occurs more frequently after ASO repair of Taussig-Bing heart than after TGA arterial switching, leading to higher reintervention rate. Resection of the commonly associated subaortic stenosis often prevents RVOTO development. PMID- 17339118 TI - Four-dimensional evaluation of implanted mechanical valve with 64-row multi detector computed tomography. PMID- 17339119 TI - Primary diffuse large B-cell lymphoma of the stomach. AB - The stomach is the extranodal site most commonly involved by non-Hodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histotype category arising in this organ. This is an aggressive lymphoma usually presenting as limited disease, being associated or not to Helicobacter pylori infection and mucosa-associated lymphoid tissue-type areas. Histopathological characteristics are similar to those reported for other diffuse large B-cell lymphomas. It occurs more frequently in males with a median age ranging between 50 and 60 years. With an adequate therapeutic strategy, its prognosis is good, with a 5-year overall survival near to 90%. Conservative treatment with anthracycline-containing chemotherapy, followed or not by involved-field radiotherapy has replaced gastrectomy as standard approach against this malignancy. Several questions on the best treatment remain unanswered. Among others, the role of rituximab, consolidation radiotherapy as well as of more conservative approaches like H. pylori-eradicating antibiotic therapy should be better defined. PMID- 17339120 TI - The gravity of unwanted thoughts: Asymmetric priming effects in thought suppression. AB - An unwanted thought appears to be cued easily by reminders in the environment but often the thought itself seems to cue nothing more than the desire to eliminate it from consciousness. This unusual asymmetry in the way unwanted thoughts are linked to other thoughts was the focus of the present research. Participants who were asked to suppress a thought or to concentrate on it completed a task assessing the influence of priming on reaction time (RT) for word/non-word judgments. Results revealed that suppression under cognitive load produced asymmetric priming: Priming with the associate of a suppressed word speeded RT for the suppressed word, but priming with a suppressed word did not speed RT for associated words. These findings suggest that thought suppression induces an unusual form of cognitive accessibility in which movement of activation toward the suppressed thought from associates is facilitated but movement of activation away from the suppressed thought to associates is undermined. PMID- 17339121 TI - Detection of respiratory pathogens in porcine lung tissue and lavage fluid. AB - The objective of this study was to compare the detection rate of bacterial agents in bronchoalveolar lavage fluid (BALF), taken without visual control, to that in affected lung tissue obtained from the same pig at necropsy. BALF and affected lung tissue were examined for Mycoplasma hyopneumoniae using PCR, and standard cultural methods were used for Actinobacillus pleuropneumoniae, Bordetella bronchiseptica, Haemophilus parasuis, Pasteurella multocida and Streptococcus suis. All pigs with a history of respiratory symptoms were submitted as live animals for routine diagnostic examination. In each animal the site of lavage, marked by injecting methylene blue, differed from the site of pneumonic lesions. M. hyopneumoniae was detected more frequently in lung tissue than in BALF in cases with moderate or severe lung lesions. The detection rates of M. hyopneumoniae were higher in the BALF of pigs with mild lesions. Cultural examination of BALF was at least as satisfactory as affected lung tissue for detecting B. bronchiseptica, H. parasuis and P. multocida. PMID- 17339122 TI - Detection of growth hormone abuse in sport. AB - OBJECTIVE: To develop a test for GH abuse in sport. DESIGN: A double blind placebo controlled study of one month's GH administration to 102 healthy non competing but trained subjects. Blood levels of nine markers of GH action were measured throughout the study and for 56 days after cessation of GH administration. Blood samples were also taken from 813 elite athletes both in and out of competition. RESULTS: GH caused a significant change in the nine measured blood markers. Men were more sensitive to the effects of GH than women. IGF-I and N-terminal extension peptide of procollagen type III were selected to construct formulae which gave optimal discrimination between the GH and placebo groups. Adjustments were made to account for the fall in IGF-I and P-III-P with age and the altered distribution seen in elite athletes. Using a cut-off specificity of 1:10,000 these formulae would allow the detection of up to 86% of men and 60% of women abusing GH at the doses used in this study. CONCLUSIONS: We report a methodology that will allow the detection of GH abuse. This will provide the basis of a robust and enforceable test identifying those who are already cheating and provide a deterrent to those who may be tempted to do so. PMID- 17339123 TI - Detection of plasmid-mediated class C beta-lactamases. AB - Plasmid-mediated class C beta-lactamases are reported from Enterobacteriaceae with increasing frequency. They likely originate from chromosomal AmpC of certain Gram-negative bacterial species and subsequently are mobilized onto transmissible plasmids. There are reports of unfavorable clinical outcomes in patients infected with these organisms and treated with broad-spectrum cephalosporins. However, unlike class A extended-spectrum beta-lactamases (ESBLs), no screening and confirmatory tests have been uniformly established for strains that produce class C beta-lactamases. Reduced susceptibility to cefoxitin is a sensitive but not specific indicator of class C beta-lactamase production. Simple confirmatory tests including tests using boronic acid compounds as specific class C beta lactamase inhibitors have recently been developed. Their utilization will enable clinical microbiology laboratories to report those strains producing plasmid mediated class C beta-lactamases as being resistant to all broad-spectrum cephalosporins, thus allowing physicians to prescribe appropriate antimicrobial therapy. PMID- 17339124 TI - A new approach to characterize grip force applied to a cylindrical handle. AB - The grip force applied to a cylindrical handle is a function of the measurement reference axis. So far, however, no attempt has been made to fully describe the exact form of this function. The objectives of this study were to examine some fundamental characteristics of grip forces and to explore the basic pattern of the grip force function. Twenty subjects (10 males and 10 females) participated in the experiment. The subjects alternately used their left and right hands to apply maximum grip forces and medium grip forces (about 40% of maximum) to a 30 mm handle. A flexible pressure sensor mat was used to measure the grip pressure. The pressure was integrated with respect to different measurement axes; this resulted in the grip force function. This study found that every gripping action produces maximum and minimum force axes; these axes are separated by about 90 degrees . The maximum force is correlated with the minimum force, but the former is generally about 1.42 times the latter. The principal grip direction is about 78 degrees from the z(h)-axis of the hand biodynamic coordinate system defined in ISO 8727 [ISO 8727. Mechanical vibration and shock - human exposure - biodynamic coordinate systems. Geneva, Switzerland: International Organization for Standardization; 1997]. More interestingly, each of the 160 sets of experimental data reasonably fit this study's proposed elliptical model. The implications of the findings are discussed. PMID- 17339125 TI - Ins and outs of therapy in limb girdle muscular dystrophies. AB - Muscular dystrophies are hereditary degenerative muscle diseases that cause life long disability in patients. They comprise the well-known Duchenne Muscular Dystrophy (DMD) but also the group of Limb Girdle Muscular Dystrophies (LGMD) which account for a third to a fourth of DMD cases. From the clinical point of view, LGMD are characterised by predominant effects on the proximal limb muscles. The LGMD group is still growing today and consists of 19 autosomal dominant and recessive forms (LGMD1A to LGMD1G and LGMD2A to LGMD2M). The proteins involved are very diverse and include sarcomeric, sarcolemmal and enzymatic proteins. With respect to this variability and in line with the intense search for a potent therapeutic approach for DMD, many different strategies have been tested in rodent models. These include replacing the lost function by gene transfer or stem cell transplantation, using a related protein for functional substitution, increasing muscle mass, or blocking the molecular pathological mechanisms by pharmacological means to alleviate the symptoms. The purpose of this review is to summarize current data arising from these preclinical studies and to examine the potential of the tested strategies to lead to clinical applications. PMID- 17339126 TI - Cytokines and cell adhesion receptors in the regulation of immunity to Trypanosoma cruzi. AB - Pathophysiology of Chagas' disease is not completely defined, although innate and adaptative immune responses are crucial. In acute infection some parasite antigens can activate macrophages, and this may result in pro-inflammatory cytokine production, nitric oxide synthesis, and consequent control of parasitemia and mortality. Cell-mediated immunity in Trypanosoma cruzi infection is also modulated by cytokines, but in addition to parasite-specific responses, autoimmunity can be also triggered. Importantly, cytokines may also play a role in the cell-mediated immunity of infected subjects. Finally, leukocyte influx towards target tissues is regulated by cytokines, chemokines, and extracellular matrix components which may represent potential therapeutic targets in infected patients. Here we will discuss recent findings on the role of cytokines, chemokines and extracellular matrix components in the regulation of innate and adaptive immunity during T. cruzi infection. PMID- 17339127 TI - The equality of quantity. AB - Do disparate dimensions of magnitude share an underlying mental representation? Two recent papers offer suggestive evidence that participants' discrimination thresholds are identical across domains. Brannon, Lutz and Cordes showed that six month-old infants' area discriminations match their number discriminations. VanMarle and Wynn demonstrated the same pattern for six-month-olds' discrimination of temporal duration. These parallels across infants' responses to number, area and time raise questions about the fundamental nature of quantity processing. PMID- 17339128 TI - A linear variation of the thermal expansivity with frequency shifts for the translational mode in ammonia solid II near the melting point. AB - We examine here our spectroscopic modification of the Pippard relation which is a linear variation of the thermal expansivity alpha(p) with the frequency shifts (1/nu)(partial differentialnu/partial differentialp)(T) close to the melting point in ammonia solid II. For this we use our calculated frequencies for the Raman mode of nu (51 cm(-1)) in ammonia solid II for the pressures of 3.65, 5.02 and 6.57 kbars. We establish this linearity between alpha(p) and (1/nu)(partial differentialnu/ partial differentialp)(T) for the pressures studied in ammonia solid II close to the melting point. The observed behaviour of ammonia solid II is explained in terms of our spectroscopic relation given here. PMID- 17339129 TI - HIV-1 and persistent clinical latency, TAR element analysis and improved method for in vitro viral reactivation. PMID- 17339130 TI - Global polio laboratory network: future pursuit and commitments. PMID- 17339131 TI - Clinical and psychosocial correlates of acute pain in herpes zoster. AB - BACKGROUND: Acute and persistent pain are the most significant clinical manifestations of herpes zoster (HZ), but the characteristics of acute pain in HZ patients have been inadequately investigated. OBJECTIVES: To correlate the severity of acute pain with clinical, demographic and psychosocial characteristics of HZ patients. STUDY DESIGN: Five hundred thirty-three patients with acute HZ were recruited by 119 dermatologists who collected medical and demographic data at diagnosis, provided counselling and therapy where appropriate and asked the patients to complete the Short Italian Questionnaire designed for comprehensive evaluation of HZ patients. RESULTS: In a univariate analysis, greater acute pain severity was significantly associated with female gender, number of dermatomes affected, presence of prodromal pain, abnormal sensations (dysesthesia), education level, anxiety and depression. Quality of life, even if greatly reduced, did not correlate with the intensity of pain. In a multivariate model, the intensity of pain was independently associated with the extent of rash (p=0.042), presence of prodromal pain (p=0.005), dysesthesia, education level (p=0.040), and depression (p<0.001), but not with gender, anxiety or quality of life. CONCLUSIONS: This study suggests that in patients with acute HZ the severity of the disease and depression at presentation are the main correlates of pain intensity. PMID- 17339132 TI - Human herpesvirus-6 (HHV-6) DNA in plasma reflects the presence of infected blood cells rather than circulating viral particles. AB - BACKGROUND: The presence of HHV-6 DNA in plasma or serum is considered a good marker of active infection. However, it is ignored whether this DNA corresponds to virus particles produced by lymphoid tissue infection or virus-free DNA released from infected circulating blood cells. OBJECTIVES: To investigate whether HHV-6 DNA in whole plasma is nonencapsidated and its amount is correlated to cellular and human herpesvirus-7 (HHV-7) DNA loads in plasma subfractions as well as in corresponding peripheral blood mononuclear cells (PBMCs). STUDY DESIGN: Whole plasma samples from immunocompromised patients were submitted to a DNase-resistance test. Plasma samples from a second group of patients were split up into three subfractions: P1 (pellet of clarification), P2 (pellet of ultracentrifugation), and S (supernatant of ultracentrifugation). HHV-6, HHV-7, and cellular DNA loads were determined in each fraction and PBMCs using specific real-time PCR. RESULTS: Among 14 whole plasma samples, the majority of HHV-6 DNA detected was unprotected against DNase, i.e. nonencapsidated. The study of 35 other plasma samples revealed that cellular DNA was present in all subfractions from all samples whereas HHV-6 DNA was detected in 13 P1, 12 P2, 10 S fractions, and HHV-7 DNA in only one P1 fraction. Accordingly, median HHV-6 DNA load was significantly higher in P1 than in P2 and S fractions. The detection of HHV-6 DNA in plasma subfractions was statistically associated with a higher HHV-6 viral load in PBMCs (p0.999 over the concentration range of 30 to 1000 ng/mL), sensitivity (limits of quantification = 15, 10, and 20 ng/mL for K, NK, and DHNK, respectively), accuracy (90-104%), and precision (RSD<8.1%) for all analytes. Two hundred and six urine specimens collected from suspected drug users were analyzed by this protocol and also screened by Neogen ELISA method to evaluate the efficiency as well as the compatibility of these two methods. Neogen ELISA showed high efficiency (98.1%), high sensitivity (90.9%), high specificity (98.9%), low false-positive rate (1.1%), and moderate false negative rate (9.1%), adopting 10 ng/mL K as the cutoff. Neogen ELISA screening followed by GC-MS analysis appeared to be a good screening-confirmation test scheme for the analysis of K in urine. Twenty of the 22 positive urine specimens contained all three analytes simultaneously, with DHNK showing the highest and K the lowest concentrations. PMID- 17339138 TI - Rapid and simultaneous determination of nifedipine and dehydronifedipine in human plasma by liquid chromatography-tandem mass spectrometry: Application to a clinical herb-drug interaction study. AB - Nifedipine (NIF), a calcium channel antagonist, is metabolized primarily by cytochrome P450 (CYP3A4) to dehydronifedipine (DNIF). As such, NIF is often used as a probe drug for determining CYP3A4 activity in human studies. A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated to simultaneously determine NIF and DNIF in human plasma using nitrendipine as the internal standard (IS). After extraction of the plasma samples by ether-n-hexane (3:1, v/v), NIF, DNIF and the IS were subjected to LC/MS/MS analysis using electro-spray ionization (ESI). Chromatographic separation was performed on a Hypersil BDS C(18) column (50 mm x 2.1 mm, i.d., 3 microm). The method had a chromatographic running time of approximately 2.5 min and linear calibration curves over the concentrations of 0.5-100 ng/mL for NIF and DNIF. The recoveries of the one-step liquid extraction method were 81.3-89.1% for NIF and 71.6-80.4% for DNIF. The lower limit of quantification (LLOQ) of the analytical method was 0.5 ng/mL for both analytes. The intra- and inter-day precision was less than 15% for all quality control samples at concentrations of 2, 10, and 50 ng/mL. The validated LC/MS/MS method has been successfully used to study pharmacokinetic interactions of NIF with the herbal antidepressant St. John's wort in healthy volunteers. These results indicated that the developed LC/MS/MS method was efficient with a significantly shorter running time (2.5 min) for NIF and DNIF compared to those methods previously reported in the literature. The presented LC/MS/MS method had acceptable accuracy, precision and sensitivity and was used in a clinical pharmacokinetic interaction study of NIF with St. John's wort, a known herbal inducer of CYP3A4. St. John's wort was shown to induce NIF metabolism with increased plasma concentrations of DNIF. PMID- 17339139 TI - Optical mammography: a new technique for visualizing breast lesions in women presenting non palpable BIRADS 4-5 imaging findings: preliminary results with radiologic-pathologic correlation. AB - The purpose of this prospective study is to determine the diagnostic accuracy of near-infrared breast optical absorption imaging in patients with Breast Imaging Reporting and Data System (BIRADS) 4-5 non-palpable lesions scheduled for biopsy, using pathology after core or excisional biopsy as a reference. The patient's breast was positioned onto a panel of red light-emitting diodes (640 nm). A soft membrane was inflated to exert a uniform pressure on the breast. Transmitted light was detected using a CCD camera. The entire acquisition sequence took 1 minute. Image processing generated dynamic images displayed in colour scale, to reveal time-dependent changes in the transmitted light intensity caused by the pressure change. Dynamic curves were classified in two categories: consistently decreasing intensity suspicious for malignancy, and sinusoidal increasing intensity considered as benign. Seventy-eight women consulting for non-palpable breast lesions were initially included in the study. An imaging-histology correlation was obtained for seventy-two patients, the remaining six patients were excluded for technical optical scan reasons. We experienced an overall sensitivity of 73% and specificity of 38%, the false negative results being mainly small size (<10 mm) infiltrating malignant lesions and ductal carcinoma in situ (DCIS). False positive results were seen in benign proliferative lesions. Dynamic optical breast imaging is a novel, low-cost, non-invasive technique yielding a new type of information about the physiology of breast lesions. Absorption is due to haemoglobin and its products, therefore reflecting the angiogenic status of breast tumours. PMID- 17339140 TI - Renal and adrenal tumours in children. AB - The differential diagnosis of renal and supra-renal masses firstly depends on the age of the child. Neuroblastoma (NBL) may be seen antenatally or in the newborn period; this tumour has a good prognosis unlike NBL seen in older children (particularly NBL in those aged 2-4 years). Benign renal masses predominate in early infancy but beyond the first year of life Wilms' tumour is the most common renal malignancy, until adolescence when renal cell carcinoma has similar or increased frequency as children get older. Adrenal adenomas and carcinomas also occur in childhood; these tumours are indistinguishable on imaging but criteria for the diagnosis of adrenal carcinoma include size larger than 5 cm, a tendency to invade the inferior vena cava and to metastasise. The most topical dilemmas in the radiological assessment of renal and adrenal tumours are presented. Topics covered include a proposed revision to the staging of NBL, the problems inherent in distinguishing nephrogenic rests from Wilms' tumour and the current recently altered approach regarding small lung nodules in children with Wilms' tumour. PMID- 17339141 TI - The current role of imaging for prostate brachytherapy. AB - Prostate brachytherapy is a radiotherapy technique for early stage prostate cancer that uses imaging guidance to place radioactive sources directly into the prostate gland. Transrectal ultrasound is used to facilitate a template-guided transperineal approach to the prostate and permits a highly conformal method of prostate radiotherapy with doses far higher than can be achieved with other radiation techniques. Maturing data has validated this technique as an acceptable treatment option with favourable and durable biochemical outcomes. The radiologist has a major role to play in the process: patient selection, guiding source delivery and follow-up after treatment all require close collaboration with colleagues in Radiation Oncology and Medical Physics. This review emphasises the specific contribution of imaging in the context of currently reported outcomes data. PMID- 17339142 TI - CT and MRI of pericardial and cardiac neoplastic disease. AB - This article reviews the pathological classification of cardiac and pericardial neoplasms, the incidence of the various tumor types, and the role of CT and MRI, including their major differences and clinical impact on patient management. PMID- 17339143 TI - Intranasal sumatriptan study with high placebo response in Taiwanese patients with migraine. AB - BACKGROUND: Triptan's efficacy in the treatment of migraine has never been reported in Taiwanese. A high placebo effect was reported in Japanese. The objective of this study was to evaluate the efficacy of intranasal sumatriptan in the acute treatment of migraine in Taiwanese patients. METHODS: Fifty-eight patients who had experienced migraine for at least 1 year were randomly assigned to 2 groups, self-administered intranasal sumatriptan 20 mg or placebo to treat a single migraine attack of moderate or severe intensity. RESULTS: A significant difference in headache relief rates between the 2 groups was observed at 30 minutes postdose (46% vs. 21%, p < 0.05). One hour postdose, 61% of sumatriptan recipients experienced headache relief compared with 43% of placebo recipients (p = 0.181). The difference in relief rates between groups diminished over time, mainly due to a high placebo response (54% at 2 hours postdose). CONCLUSION: Our study suggests that ethnicity might have a role in placebo response, and highlights the importance of a placebo group in acute migraine trials. However, the small sample size in this study should also be taken into consideration. PMID- 17339144 TI - Cerebral oxygenation during hypoxia and resuscitation by using near-infrared spectroscopy in newborn piglets. AB - BACKGROUND: Hypoxic events and cardiac arrest may cause brain damage in critical infants. This study investigated cerebral tissue oxygenation and oxygen extraction in a piglet model of hypoxic events, cardiac arrest and effects of resuscitation. METHODS: For the hypoxia experiment, anesthetized newborn piglets were randomized to a hypoxia group (n = 8) with decreasing ventilatory rate to 0, and a control group (n = 8) with no hypoxic conditions. Regional cerebral tissue oxygen saturation (rScO2, detected by near-infrared spectroscopy) and oxygen saturation were recorded every 5 minutes for 100 minutes. Fractional cerebral tissue oxygen extraction (FTOE) was calculated as (arterial oxygen saturation [SaO2] - rScO2)/SaO2. For the resuscitation experiment, animals were grouped as hypoxia-no CPR (n = 4), control-no CPR (n = 4), and control-CPR (n = 4) after cardiac arrest. Standard cardiopulmonary resuscitation (CPR) was performed on the control-CPR group and observed for 30 minutes. RESULTS: Immediate and significant changes in rScO2, and gradual changes in FTOE were observed during the hypoxia experiment. In the resuscitation experiment, no significant differences in rScO2 were found between groups. However, the highest FTOE was observed in the control CPR group. CONCLUSION: Noninvasive monitoring of rScO2 and evaluating FTOE changes during hypoxia and resuscitation may help clinicians evaluate brain tissue oxygenation and viability. PMID- 17339145 TI - Outcome and prognostic factors of decompressive hemicraniectomy in malignant middle cerebral artery infarction. AB - BACKGROUND: Whether decompressive hemicraniectomy is an appropriate treatment for malignant middle cerebral artery (MCA) infarction is still a controversial issue. The aims of our study were to determine survival rate and functional out-come and to determine factors associated with survival rates and functional outcome in patients with malignant MCA infarction. METHODS: From January 2000 to December 2003, 60 patients with malignant MCA infarction were included in the study. All the patients in the study underwent a large ipsilateral craniectomy and a large duroplasty for decompression. The infarction territory was evaluated by either diffusion-weighted MRI or computed tomography. Clinical neurologic presentation was evaluated using the Glasgow coma scale. Functional outcome was evaluated with the Barthel index (BI) and the Glasgow outcome scale (GOS) during the follow-up period of 12 months. RESULTS: Mortality was 20% (12 patients) during 30 days and 26.6% during 12 months' follow-up. The factors associated with higher mortality were age > or = 60 years, involvement of more than 1 vascular territory, clinical herniation signs before surgery and treatment after 24 hours of ictus. Mean GOS was 3.3 +/- 1.7 during the 12-month follow-up period. Mean BI was 65.1 +/- 40.1. Twenty-nine (65.9%) patients had favorable outcome (BI > or = 60). The factors associated with favorable outcome were age < 60 years, dominant hemisphere infarction, regaining of consciousness within 7 days after operation, being without respiratory failure and treatment within 24 hours of ictus before clinical signs of herniation. CONCLUSION: Decompressive hemicraniectomy may be a useful procedure in patients with malignant MCA infarction. Age, clinical signs of herniation and timing of surgery were the prognostic factors associated with mortality and functional outcome. PMID- 17339146 TI - Nonarteritic ischemic optic neuropathy. AB - BACKGROUND: To describe the systemic and visual characteristics and prognosis in patients with nonarteritic ischemicoptic neuropathy (NAION) undergoing different treatments. METHODS: Retrospective chart review was performed in Kaohsiung Veterans General Hospital patients from 1995-2005 with a clinical diagnosis of NAION, including nonarteritic anterior ischemic optic neuropathy and posterior ischemic optic neuropathy (PION). There were 14 PION patients out of a total of 103 cases. The average age at disease attack was 61 years old, and the ratio of males to females was 1.24:1. Comorbid systemic diseases and visual function were recorded at both initial presentation and the later follow-up period. The final results were recorded and compared by the different treatments they received in 4 groups. RESULTS: In all, NAION usually affected people > 50 years old, without any difference between sexes. Presenting visual acuity, age, and different treatment modes had no direct influence on the final visual outcome. The most significant associated factor was hypertension. CONCLUSION: NAION is a serious illness; the visual deficit persists even with aggressive treatment. PMID- 17339147 TI - Using desmoglein 1 and 3 enzyme-linked immunosorbent assay as an adjunct diagnostic tool for pemphigus. AB - BACKGROUND: Pemphigus is an acquired autoimmune intraepidermal blistering disease that is divided into 2 major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with pemphigus have circulating anti-desmoglein (Dsg)1 and/or anti-Dsg3 IgG autoantibodies. Recently, a novel commercial enzyme-linked immunosorbent assay (ELISA) against Dsg1 and Dsg3 has been established and found to be extremely sensitive and specific. To date, the usefulness of Dsg1 and Dsg3 ELISA in the diagnosis of pemphigus in the Taiwanese population has never been reported. METHODS: Serum samples were obtained from 143 patients, including 20 patients with PV, 9 patients with PF, 72 patients with bullous pemphigoid, 1 patient with dermatitis herpetiformis and 41 patients with non-autoimmune blistering diseases. They were tested for anti-Dsg1 and anti-Dsg3 reactivity by ELISA. RESULTS: Seventeen of 20 PV sera (85%) exceeded the cut-off value of Dsg3 ELISA, and 9 of 9 PF sera (100%) exceeded the cut-off value of Dsg1 ELISA, while only 1 (0.88%) and 3 (2.6%) of 114 non-pemphigus sera exceeded the cut-off values of Dsg3 and Dsg1 ELISAs, respectively. Thus, the sensitivity and specificity of Dsg3 ELISA were 85% and 99.1%, while the sensitivity and specificity of Dsg1 ELISA were 100% and 97.4%, respectively. The correlation between ELISA scores and disease activity along the time course was examined in 6 PV patients and 1 PF patient, and the result was equivocal. CONCLUSION: Dsg1 and Dsg3 ELISAs provide a simple, highly sensitive and specific method that can serve as a useful adjunct tool for the initial diagnosis of pemphigus. PMID- 17339148 TI - Primary lymphohistiocytic variant of anaplastic large cell lymphoma of the stomach. AB - Here, we report an unusual case of gastric anaplastic large cell lymphoma (ALCL), lymphohistiocytic variant, in a 70-year-old female patient who presented with epigastric pain, tarry stool and body weight loss. Endoscopic and imaging findings revealed a Bormann type II tumor in the stomach with perigastric lymphadenopathy and multiple tumor nodules in the liver. Total gastrectomy and liver biopsy were performed. Histologically, both gastric and hepatic tumors demonstrated anaplastic large neoplastic cells scattered among numerous reactive histiocytes. Immunostaining of these tumor cells reacted positively for CD30, CD3, CD45 RO/UCHL1, and negatively for epithelial membrane antigen, CD68, lysozyme, CD15, CD79a, CD138, PAX5 and anaplastic lymphoma kinase. Both the morphologic and immunophenotypic findings supported the diagnosis of gastric ALCL of lymphohistiocytic variant with liver metastasis. This patient then received chemotherapy and was still alive after 17 months of follow-up, without evidence of residual disease. PMID- 17339149 TI - Malignant ganglioneuroma arising from mediastinal mixed germ cell tumor. AB - Mixed germ cell tumors with non-germ cell malignant components rarely occur in the anterior mediastinum. We report a case of a 34-year-old man who presented with an anterior mediastinum mass. Mixed germ cell tumor was initially diagnosed based on the pathologic findings of germinoma on thoracoscopic biopsy and clinical findings of elevated serum alpha-fetoprotein and beta-human chorionic gonadotropin. The patient received preoperative chemotherapy and subsequent complete resection of the residual tumor. Pathologic examination of the excised specimen showed predominantly malignant ganglioneuroma and small residual foci of teratoma. To our knowledge, this is the first reported case of a malignant ganglioneuroma arising from mediastinal mixed germ cell tumor. PMID- 17339150 TI - Primary leiomyoma of the fallopian tube: preoperative ultrasound findings. AB - Leiomyoma of the fallopian tube is extremely rare. Most cases are asymptomatic and found incidentally at autopsy or unrelated operation. These leiomyomas tend to be singular, small, and unilateral, with a resultant rare preoperative diagnosis. They are often managed with laparotomy, as seen in the literature review. Therefore, preoperative imaging is never reported. We describe a case of leiomyoma of the fallopian tube, which was suspected before operation and treated by laparoscopic approach. Transvaginal ultrasound clearly showed a hypoechoic solid mass separate from the left ovary and uterus in a 44-year-old woman. Color Doppler ultrasound detected low impedance flow in this mass. Diagnostic laparoscopy and the follow-up laparoscopic salpingoectomy revealed a primary leiomyoma of the fallopian tube. We conclude that powerful ultrasound could be helpful in diagnosing rare gynecologic disorders but laparoscopy can be used for definite diagnosis and management of such disorders. PMID- 17339151 TI - Idiopathic polypoidal choroidal vasculopathy. AB - Idiopathic polypoidal choroidal vasculopathy (IPCV) has been recognized as a peculiar form of choroidal neovascularization. The clinical features of recurrent serous retinal leakage and retinal hemorrhage may vary from single lesion to multifocal, from self-limited to recurrent. Caucasian and Japanese patients with IPCV have been reported in the literature. However, research and case reports about IPCV in Chinese patients are relatively rare. We present 2 Chinese patients with IPCV in Taiwan with 2 different clinical pictures and visual outcomes during long-term follow-up. Further study for the etiology, clinical courses and treatments of the different subtypes of IPCV in Chinese is necessary. PMID- 17339152 TI - Ulinastatin alone does not reduce caspase 3-mediated apoptosis in protease positive Aeromonas hydrophilia-induced sepsis. AB - BACKGROUND/PURPOSE: To evaluate the effect of ulinastatin, a protease inhibitor, on survival and apoptosis in protease-positive Aeromonas hydrophilia (PPAH) induced sepsis. METHODS: Thirty mice were randomly allocated to receive intraperitoneal injection of either phosphate buffered saline (PBS) (control mice, n = 10) or PPAH (PPAH mice, n = 20). After 30 minutes, control mice received an additional intraperitoneal PBS injection, 10 PPAH mice received intraperitoneal PBS injection (non-treated PPAH mice), and the remaining 10 PPAH mice received an intraperitoneal injection of ulinastatin (ulinastatin-treated PPAH mice). RESULTS: Survival at 24 hours was 100% in control mice, and 35% (p < 0.05) in PPAH mice; the survival rate in non-treated and ulinastatin-treated PPAH mice were 30% and 40% (p > 0.05), respectively. The thymus weight (mg) decreased significantly in PPAH mice (51.1 +/- 14.9) compared to control mice (69.7 +/- 14.4; p < 0.001); there was no difference between ulinastatin-treated (52 +/- 13.9; p > 0.05) and non-treated PPAH mice (50.4 +/- 16). The thymus gland cell count reduced significantly in PPAH mice (8.1 +/- 4.7 x 10(7)) compared to control mice (12.8 +/- 6.6 x 10(7); p < 0.01), and immunofluorescence analysis demonstrated that the reduced cells were mostly CD4+ CD8+, in contrast to the increase in CD4+ CD8- cells. There was no difference in cell count between ulinastatin-treated (8.7 +/- 4.9 x 10(7)) and non-treated PPAH mice (7.4 +/- 4.6 x 10(7); p > 0.05). Caspase 3-mediated apoptosis was not detectable in control mice in contrast to the pronounced manifestation in PPAH mice. CONCLUSION: PPAH induced sepsis has a high mortality that is related to lymphocyte apoptosis. Ulinastatin alone does not significantly reduce caspase 3-mediated lymphocyte apoptosis. PMID- 17339153 TI - Unappreciated HLA antibodies in adult immune thrombocytopenic purpura. AB - BACKGROUND/PURPOSE: Immune thrombocytopenic purpura (ITP) is an autoimmune disease. Platelet refractoriness is frequently seen in patients with ITP. Platelets express platelet-specific antigens and human leukocyte antigens (HLA). Platelet antibodies to platelet-specific antigens and HLA may be present, but HLA antibodies in patients with ITP have rarely been reported. METHODS: Sera from 44 adult patients with ITP were screened for platelet antibodies by two flow cytometric assays. In method I, platelets from normal donor platelets were used as target cells to screen both platelet-specific antibodies and HLA class I antibodies. In method II, the FlowPRA Class I Screening Test kit was used to screen HLA class I antibodies. Fluorescein isothiocyanate (FITC)-conjugated sheep anti-human IgG Fc was used as the staining reagent in both methods. The negative serum control was from one of the normal males with AB blood group who had never received a transfusion. Sera from a pool of five highly sensitized patients were used as the positive control. RESULTS: Of the 44 sera from patients with ITP, 31 (70.5%) were method I positive, and 28 (63.6%) were method II positive. There was no significant difference between the results of method I and method II (p = 0.439). The distribution of the results of these two tests was: both tests positive in 22 sera, method I positive and method II negative in nine sera, method I negative and method II positive in six sera, and both tests negative in seven sera. The mean platelet counts of patients with positive (41.0 +/- 40.0 x 10(9)/L) and negative (40.4 +/- 26.8 x 10(9)/L) tests by method I did not differ significantly (p = 0.643). The mean platelet counts of patients with (36.7 +/- 31.5 x 10(9)/L) and without (48.1 +/- 43.6 x 10(9)/L) HLA class I antibodies did not differ significantly (p = 0.59). CONCLUSION: HLA class I antibodies are frequently found in ITP. The screening of platelet antibodies including platelet specific antibodies and unappreciated HLA class I antibodies is warranted in patients with ITP. PMID- 17339154 TI - Risk factors affecting in-hospital mortality in patients with nosocomial infections. AB - BACKGROUND/PURPOSE: Nosocomial infection (NI)-associated death is an important issue for both patients and clinicians, and is of emerging importance in public health. This study investigated the factors associated with in-hospital deaths among patients with NI. METHODS: Between July 1, 2002 and June 30, 2003, a total of 1574 patients with NI at National Taiwan University Hospital were enrolled to investigate the factors associated with fatal outcome. Host factors, hospital services, surgical and medical interventions, microbial factors, infection sites, and the treatment and complications of NI were analyzed retrospectively. RESULTS: During the study period, 554 of the 1574 patients died (mortality rate, 28.3%). NI was directly involved in 80.5% of them (n = 446), and over two-thirds (67.9%) of deaths occurred within 2 weeks of NI onset. Sixteen variables were statistically implicated as independent factors significantly associated with mortality. Host factors included higher disease severity (p < 0.0001), liver cirrhosis (p < 0.0001), solid tumors (p < 0.0001), chronic lung disease (p = 0.003), and congestive heart failure (p = 0.005). Hospital and interventional factors included intensive care hospitalization (p = 0.002), longer hospitalization before NI onset (p = 0.004), hemodialysis (p = 0.0003), arterial line insertion (p < 0.0001), urinary catheterization (p < 0.0001), and central venous catheterization (p = 0.001). Blood stream infections (p < 0.0001), NI due to Candida (p < 0.0001), and multiple (> or = 2) episodes of NI (p < 0.0001) were significant risk factors for death, as were occurrence of NI-associated septic shock (p < 0.0001) and disseminated intravascular coagulation (p < 0.0001). No significant associations of mortality with age, sex, species of bacteria, multi antibiotic resistant bacteria, regimen for initial treatment, or multiple antibiotic therapy were evident. CONCLUSION: Measures that prevent the occurrence of NI, such as improving the immunity status of the host, removal of catheters as soon as possible, and implementing an infection control program, could reduce the risk of in-hospital deaths attributable to NI. PMID- 17339155 TI - Pancreaticobiliary anomalies is the leading cause of childhood recurrent pancreatitis. AB - BACKGROUND/PURPOSE: To explore the etiology, age and gender distribution, complications, and prognosis of recurrent pediatric pancreatitis. METHODS: Between 1993 and 2005, 92 children were hospitalized at the National Taiwan University Hospital with pancreatitis. Only 25 diagnosed with recurrent pancreatitis, based on two or more episodes of pancreatitis, elevated serum amylase and/or lipase levels > or = 3 times the upper limit of normal, radiographic evidence, and clinical symptoms, were enrolled. RESULTS: A total of 85 episodes of pancreatitis in 25 patients (16 girls, 9 boys; mean age, 9.5 +/- 4.4 years; 3.4 +/- 1.9 episodes per person) were documented. The recurrence rate of pediatric pancreatitis was 27.2%. Recurrent pancreatitis was associated with pancreaticobiliary structural anomalies (n = 7), biliary stones or sludge (n = 4), hyperlipidemia (n = 3), pseudopapillary tumor of the pancreas (n = 2), trauma (n = 2), hypoxic encephalopathy with recurrent bacteremia and sepsis (n = 1), and idiopathic (n = 6). The age and gender distribution according to etiologies were not different (p = 0.301 for age, p = 0.137 for gender). Complications included cholangitis or cholestasis (16%), pancreatic necrosis (16%), pseudocyst formation (12%), shock (8%), hemorrhagic pancreatitis (4%), and diabetes mellitus (4%). No patient died of recurrent pancreatitis. Long-term morbidity after recurrent pancreatitis presented as gout, diabetes mellitus, non-alcoholic steatohepatitis, and chronic pancreatitis. CONCLUSION: For children who suffer from recurrent pancreatitis, pancreaticobiliary structural anomalies should be considered first. PMID- 17339156 TI - Validity of sentinel lymph node biopsy in Taiwanese breast cancer patients. AB - BACKGROUND/PURPOSE: The clinical validity of sentinel lymph node (SLN) biopsy in Taiwanese breast cancer patients from 16 institutes in two consecutive periods was analyzed. METHODS: Data from the initial period between January 3, 1999 and July 2004 and data from the later period after August 2004 to February 2005 were compared. Data on the use of a tracer, SLN identification, harvest and examination, false negative rate (FNR) and the number of patients spared axillary lymph node dissection (ALND) were analyzed. RESULTS: A total of 3308 patients with clinical axilla negative breast cancer underwent SLN biopsies in 16 hospitals (11 in both periods and 5 in the period before August 2004). Comparison of data from the two periods revealed that in the later period, use of combined blue dye and isotope tracer increased from 40% to 80%, the 95% SLN biopsy success rate increased from 50% to 80%, hospitals conducting intraoperative SLN examination increased from 80% to 93%, and the 95% match to permanent section rate increased from 30% to 80%. In the initial period, eight hospitals had less than 7% FNR, while in the later period this had decreased to 4.1% in these hospitals. Another three hospitals had FNR greater than 7% in the initial period, which had decreased to 0% in the later period. Hospitals with more than 100 cases of SLN biopsy had an average 3.8% FNR, whereas hospitals with less than 100 cases of SLN biopsy experience had an 8.2% FNR (p < 0.01). CONCLUSION: This study found that the SLN biopsy success rate increased after the use of combined tracers and with experience. FNR was controlled to within 5% among breast surgeons with accumulated experience exceeding 100 cases. It is recommended that ALND-sparing surgery be suspended temporarily in hospitals with FNR greater than 5%. PMID- 17339157 TI - Effective epidural blood patch volumes for postdural puncture headache in Taiwanese women. AB - BACKGROUND/PURPOSE: Epidural blood patch (EDBP) is the most commonly used method to treat postdural puncture headache (PDPH). The optimal or effective blood volume for epidural injection is still controversial and under debated. This study compared the therapeutic efficacy of 7.5 mL blood vs. 15 mL blood for EDBP via epidural catheter injection. METHODS: Thirty-three patients who suffered from severe PDPH due to accidental dural puncture during epidural anesthesia for cesarean section or epidural analgesia for labor pain control were randomly allocated into two groups. EDBP was conducted and autologous blood 7.5 mL or 15 mL was injected via an epidural catheter in the semi-sitting position in Group I (n = 17) and II (n = 16), respectively. For all patients in both groups, the severity of PDPH was registered on a 4-point scale (none, mild, moderate, severe) and assessed 1 hour, 24 hours and 3 days after EDBP. RESULTS: There was no significant difference between the two groups of patients at all time points with respect to the severity of PDPH. Two patients in Group I and nine in Group II developed nerve root irritating pain during blood injection (p < 0.05). No systemic complications were noted in both groups of patients throughout EDBP injection. CONCLUSION: We conclude that injection of 7.5 mL autologous blood into the epidural space is comparable to 15 mL blood in its analgesic effect on PDPH, but with less nerve root irritating pain during injection. PMID- 17339158 TI - Oral verruciform xanthoma: a clinicopathologic study of 15 cases. AB - BACKGROUND/PURPOSE: Oral verruciform xanthoma (VX) is an uncommon oral mucosal lesion. This retrospective study evaluated the clinical and histopathologic features of 15 oral VXs occurring in Taiwanese patients. METHODS: Fifteen consecutive cases of oral VX were collected from January 1988 to December 2005. Clinical data and microscopic features of these cases were reviewed and analyzed. RESULTS: The mean age of patients was 45 years (range, 18-79 years). There were eight male and seven female patients. Seven (46.6%) cases occurred on the gingiva, four (26.7%) on the tongue, and four (26.7%) on the buccal or vestibular mucosa. The greatest mean dimension of the lesions was 0.8 cm (range, 0.3-2.0 cm). Three patients had concomitant other oral mucosal lesions such as oral submucous fibrosis, squamous cell carcinoma, and erosive oral lichen planus. Microscopically, all specimens showed varying degrees of surface parakeratosis and the accumulation of numerous foam cells in the connective tissue papillae among uniformly elongated epithelial ridges. Individuals or aggregates of foam cells were also found underneath the epithelial ridges in nine (60%) cases. When the oral VX lesions were further classified into three types according to the microscopic surface architecture, seven (47%) lesions were of the verrucous type, three (20%) the papillary type, and five (33%) the flat type. All patients received surgical excision of the lesions and no recurrence was noted during follow-up of up to 18 years. CONCLUSION: Oral VXs occur more frequently in the fifth decade of life. The more commonly affected site is the gingiva. The treatment of choice for oral VXs is surgical excision. The prognosis is excellent and recurrence was not seen in this study. PMID- 17339159 TI - Estimation of seroprevalence of hepatitis B virus and hepatitis C virus in Taiwan from a large-scale survey of free hepatitis screening participants. AB - BACKGROUND/PURPOSE: Taiwan is a hyperendemic area of liver diseases. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the two major etiologies of liver diseases in Taiwan. This study investigated the seroprevalence of HBV and HCV in Taiwan. METHODS: Since 1996, a series of outreach community-based screening programs for liver diseases have been available to the general population aged > or = 18 years. Blood samples were obtained from the subjects and sent for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) tests. RESULTS: The prevalence of HBsAg(+) was 17.3% (27,210/157,720), while the prevalence of anti-HCV(+) was 4.4% (6904/157,720). Geographic variation in HBV and HCV seroprevalence was found, with the highest anti-HCV positive rate in Miaoli County, Chiayi County, Chiayi City, and Yunlin County, and the highest HBsAg positive rate in Keelung City and Yilan City. The HBsAg positive rate progressively decreased after the age of 50 years, while the anti-HCV positive rate progressively increased after the age of 20 years. The estimated total number of HBsAg carriers in the general population > 20 years old is 3,067,307, while the estimated number of anti-HCV positive patients is 423,283. CONCLUSION: This study estimated a 17.3% seroprevalence of HBV and a 4.4% seroprevalence of HCV in Taiwan. Significant geographic variations in the seroprevalence of HBV and HCV were found. These data suggest the importance of modifying programs for the prevention and treatment of chronic viral hepatitis in Taiwan to reflect its varying prevalence and epidemiology. PMID- 17339160 TI - Eosinophilic pleural effusion as the first presentation of angioimmunoblastic T cell lymphoma. AB - Eosinophilic pleural effusion (EPE), defined as pleural effusion that contains at least 10% eosinophils among the leukocytes, can be a manifestation of a great variety of diseases. However, eosinophilia is a relatively rare finding in malignant pleural effusions, and it has been used as an indicator of good prognosis. In clinical experience, very few cases of malignant lymphomas accompanied by EPE have been reported. In this report, we present an 82-year-old otherwise healthy man with the initial presentation of left EPE. Pleural biopsy could not yield a definite diagnosis initially. Hookworm ova were also found in the stool and parasite associated with EPE was suspected. However, after anti parasitic agent treatment with mebendazole, the pleural effusion did not improve. Six months later, bilateral neck, axillary and inguinal lymphadenopathy developed, and lymph node biopsy confirmed the diagnosis of angioimmunoblastic T cell lymphoma, with positive CD10 expression. Therefore, we retrospectively carried out CD10 staining of the sample obtained from pleural biopsy and the positive result confirmed that the etiology of EPE was due to malignant T cell lymphoma. The patient refused chemotherapy and he died 1 month later. PMID- 17339161 TI - Neonatal listeriosis. AB - In Western developed countries, Listeria monocytogenesis not an uncommon pathogen in neonates. However, neonatal listeriosis has rarely been reported in Taiwan. We describe two cases collected from a single medical institute between 1990 and 2005. Case 1 was a male premature baby weighing 1558 g with a gestational age of 31 weeks whose mother had fever with chills 3 days prior to delivery. Generalized maculopapular rash was found after delivery and subtle seizure developed. Both blood and cerebrospinal fluid culture collected on the 1st day yielded L. monocytogenes. In addition, he had ventriculitis complicated with hydrocephalus. Neurologic development was normal over 1 year of follow-up after ventriculoperitoneal shunt operation. Case 2 was a 28-weeks' gestation male premature baby weighing 1180 g. Endotracheal intubation and ventilator support were provided after delivery due to respiratory distress. Blood culture yielded L. monocytogenes. Cerebrospinal fluid showed pleocytosis but the culture was negative. Brain ultrasonography showed ventriculitis. Sudden deterioration with cyanosis and bradycardia developed on the 8th day and he died on the same day. Neonatal listeriosis is uncommon in Taiwan, but has significant mortality and morbidity. Early diagnosis of perinatal infection relies on high index of suspicion in perinatal health care professionals. PMID- 17339162 TI - Inflammatory pseudotumor of the sinonasal tract. AB - Inflammatory pseudotumors (IPTs) are a clinically and histologically diverse group of lesions characterized by a tumor mass of acute and chronic inflammatory cells with a variable fibrous response. IPTs most commonly involve the lung and orbit, but rarely the sinonasal tract. We report a 68-year-old male with an IPT of the sinonasal tract presenting as nasal obstruction and postnasal dripping for several years. A gray-white soft mass was noted in the right nasal cavity. Computed tomography revealed a solid mass filling the right nasal cavity and maxillary sinus. Caldwell-Luc operation with ethmoidectomy (right) was conducted to resect the mass en bloc. Pathology revealed admixture of plasma cells, lymphocytes and eosinophils, confirming the diagnosis of IPT. The patient remained symptom-free over 4 years of follow-up. Awareness of the clinical presentations, histopathologic features and treatment of choice of this rare disease entity is necessary to distinguish it from malignancy and avoid unnecessary management. PMID- 17339163 TI - Mutational analysis of PTPN11 gene in Taiwanese children with Noonan syndrome. AB - Noonan syndrome (NS) is an autosomal dominant disorder presenting with characteristic facies, short stature, skeletal anomalies, and congenital heart defects. Mutations in protein-tyrosine phosphatase, nonreceptor-type 11 (PTPN11), encoding SHP-2, account for 33-50% of NS. This study screened for mutations in the PTPN11 gene in 34 Taiwanese patients with NS. Mutation analysis of the 15 coding exons and exon/intron boundaries was performed by polymerase chain reaction and direct sequencing of the PTPN11 gene. We identified 10 different missense mutations in 13 (38%) patients, including a novel missense mutation (855T>G, F285L). These mutations were clustered in exon 3 (n = 6) encoding the N SH2 domain, exon 4 (n = 2) encoding the C-SH2 domain, and in exons 8 (n = 2) and 13 (n = 3) encoding the PTP domain. In conclusion, this study provides further support that PTPN11 mutations are responsible for Noonan syndrome in Taiwanese patients. PMID- 17339164 TI - Hand, foot and mouth disease complicated with central nervous system involvement in Taiwan in 1980-1981. AB - Sixteen cases from the 1980-1981 Taiwan outbreak of hand, foot and mouth disease (HFMD) associated with central nervous system involvement were identified: nine had polio-like syndrome, four had encephalitis or encephalomyelitis, one had cerebellitis, and two had aseptic meningitis. They all had fever, five (31%) had documented myoclonic jerk, and 15 (93%) had HFMD. Their mean blood leukocyte count was 12,490/microL, and five (31%) had leukocytosis (> 15,000/microL); mean cerebrospinal fluid (CSF) leukocyte count was 156/microL, CSF protein was 57 mg/dL and CSF glucose was 57 mg/dL. Two patients with HFMD plus encephalitis died within 1 day of hospitalization, and one of them had acute cardiopulmonary failure mimicking myocarditis. Twenty years later, at least one male patient had sequelae of polio-like syndrome and was therefore exempted from military service. Clinical severity was comparable to the 1998 EV71 epidemic. PMID- 17339165 TI - Comparing child mortality in Taiwan and selected industrialized countries. AB - This study compares the mortality rates of children in Taiwan with selected industrialized countries, and identifies the explanations of cross-national variations. We ranked all comparison countries by infant mortality rate (IMR) and under-five mortality rate (U5MR). Multiple regression models were used to examine the relationship of child mortality with gross domestic product, national health expenditure, public social expenditure, and Gini coefficient. For 2002, the IMR and U5MR in Taiwan were 6 per thousand and 8 per thousand, respectively, both ranking 20th among 21 industrialized countries. In explaining cross-national differentials in child mortality, we found that Gini coefficient, an indicator of income inequality, was positively associated with IMR and U5MR, and that social expenditure was negatively associated with U5MR. Our study shows that prevention of child mortality in Taiwan has not yet reached the highest attainable standard, and underscores the importance of a fairer income distribution and social investment in child health care. PMID- 17339166 TI - Mechanisms of cough syncope as evaluated by valsalva maneuver. AB - Successful treatment of cough syncope depends on the correction of various pathogenetic mechanisms among different patients. The valsalva maneuver (VM), which elicits hemodynamic responses mimicking coughs, has potential for investigating the individual pathogenesis of cough syncope. Eighteen consecutive patients suffering from cough-induced syncope were examined. All patients were asked to cough and to perform VM several times under continuous cerebral blood flow velocity and blood pressure (BP) monitoring by transcranial Doppler and finger plethysmography. Eight patients demonstrated abnormal VM characterized by the absent BP overshoot following the relief of straining. Patients demonstrating abnormal VM had delayed BP recovery after cough (median, 16.4; range, 8.7-25.6 seconds) compared to those demonstrating normal VM (2.6, 1.3-3.8 seconds, p < 0.001). Seven of the 10 patients exhibiting normal BP overshoot during VM had stenotic arterial lesions in the cerebral or coronary circulation, whereas only one of the eight patients demonstrating absent BP overshoot had coronary artery disease (70% vs. 12.5%, p = 0.025). Other clinical profiles, body mass index, frequency of obstructive pulmonary disease and valsalva ratio did not differ between patients featuring normal and absent BP overshoot. In conclusion, the pathogenesis of cough syncope could be different between patients with normal and abnormal VM responses. Patients who had no BP overshoot during VM sustained prolonged hypotension after cough. The VM helps in discriminating among pathogenic mechanisms and guiding investigation and treatment for cough syncope patients. PMID- 17339167 TI - Urinary stone analysis of 1,000 patients in southern Taiwan. AB - Urolithiasis is a common urologic disease. Stones may occur in the kidney, ureter, or urinary bladder. We collected 1,000 stone samples in the subtropical area of southern Taiwan. Stone components were analyzed by Fourier transform infrared spectroscopy. Mixed components of calcium oxalate and calcium phosphate were the most common form of stones (52.3%), followed by calcium oxalate (27.8%) and calcium phosphate (9.3%). Uric acid stones accounted for 7.6%. Magnesium ammonium phosphate stones accounted for 3.0%. Only one cystine stone was found. In the study of urinary stone formation mechanism and prevention of recurrent urolithiasis, knowing the stone composition is important. PMID- 17339168 TI - Comparison of different surgical options in the treatment of pilonidal disease: retrospective analysis of 175 patients. AB - Pilonidal sinus disease is a benign disorder with an unidentified etiology and is observed mainly in young adults. It is an important health problem because it causes work loss. Although various nonsurgical treatment options have been tried up to date, there is a consensus on surgical intervention to treat the disease today. The optimal surgical method should be simple, associated with short hospital stay and low recurrence rates. In this study, patients who have undergone different surgical treatment methods due to pilonidal disease were retrospectively analyzed. The medical records of 175 patients who were operated on between 2002 and 2005 at the General Surgery Departments of Gaziosmanpasa University Medical School and Bartin State Hospital for pilonidal disease were reviewed for treatment option, postoperative complications, hospitalization time, work-off periods, and recurrence rates. The patients consisted of 150 (85.3%) males with a mean age of 26.47 +/- 7.78 years. Marsupialization was applied to 82 (46.9%), unroofing to 20 (14.7%), primary closure to 29 (16.6%), and Limberg flap to 44 (25.1%) patients. The longest hospitalization period of 3.61 +/- 1.08 days was observed in the Limberg flap group. The longest return to work period (20.12 +/- 5.1 days) was observed in the marsupialization group. Both differences were significant. The highest complication rate was observed among the primary closure group (31%) followed by the patients treated by Limberg flap technique (15.8%). In the primary closure group, infection was detected in five (17.2%) and wound dehiscence in four (13.8%) individuals. The highest complication rates (31.03%) and recurrences (13.8%) were observed in the primary closure group. Various operative methods utilized in the treatment of pilonidal disease are associated with a number of advantages and disadvantages. Postoperative complication rates of unroofing and marsupialization are low, but require long wound care. In our study, we did not observe any recurrence among the patients treated by unroofing, but experienced a high recurrence ratio among subjects treated by marsupialization. In addition, there were high complication rates in the primary closure and Limberg flap groups. So, the best option is to explain the advantages and disadvantages of the available surgical methods and respect the patient's decision. PMID- 17339169 TI - Psychosocial features at different periods after childbirth. AB - The purpose of this study was to examine and compare first-time mothers' postpartum stress, depression, social support, and health status over the first 6 weeks following discharge from hospital after childbirth. Four hundred and thirty five women were enrolled from clinics and hospitals in Kaohsiung City, southern Taiwan. The study showed that three items - "the baby getting sick suddenly", "the unpredictability of the baby's schedule", and "the flabby flesh of my belly" - were consistently perceived to be among the top five postpartum stressors by women, regardless of which postpartum week it was. Most women had minimal depression with 71.83% in the sixth week to 81.58% in the first week. Women perceived a high level of social support and their greatest amount of support was from family. A range of women from 25.71% in the fifth week to 32.39% in the second week of postpartum was categorized as having minor psychiatric morbidity. However, the results indicated that the mean scores for postpartum stress and social support did not differ significantly for the women over the 6 postpartum weeks. Women with different depression levels and health status over the 6 postpartum weeks had no significant differences either. Insight into the results of this study provides a framework for additional research that a longitudinal design is needed from immediate childbirth to 1 year postpartum in order to explore the fluctuations of women's psychosocial factors. PMID- 17339170 TI - Red umbilicus as a clinical manifestation in a 19-month-old girl with typhoid colonic perforation. AB - Redness of the umbilicus is usually considered to be a reliable sign of underlying gangrenous bowel or peritonitis in tiny infants but seldom among non neonatal patients. We report a 19-month-old girl with final diagnosis of typhoid colonic perforation who initially presented with abdominal distention and umbilical erythema on arrival at our emergency department. The redness of umbilicus diminished gradually after laparotomy. Thin abdominal wall, severe intra-abdominal soiling, and polymicrobial infection accounted for the inflammatory process spreading to the skin of the umbilicus. Because of its rarity beyond the neonatal period, prompt diagnosis depends on maintaining a high index of suspicion when the abdomen is distended and suddenly tender to palpation. PMID- 17339171 TI - Orbital metastasis from urothelial carcinoma of the urinary bladder. AB - Radical cystectomy with ileal conduit diversion remains the standard treatment for invasive bladder cancer. We report a patient with urothelial carcinoma of the urinary bladder and found metastasis to the orbit post radical cystectomy and ileal conduit diversion presenting as blurred vision and diagnosed by open biopsy. The orbit is an infrequent site of metastasis from bladder cancer cells. To the best of our knowledge, there are fewer than 10 case reports of orbital metastasis from urothelial carcinoma reported in the English medical literature. PMID- 17339172 TI - Leukemoid reaction resulting from granulocyte colony-stimulating factor producing urothelial carcinoma of the renal pelvis. AB - Leukemoid reaction is defined as a reactive leukocytosis in response to infection, inflammation, or therapeutic agents such as growth factors and malignancy. We report a case of leukemoid reaction resulting from granulocyte colony-stimulating factor producing urothelial carcinoma of the renal pelvis as evidenced on immunohistochemical analysis. PMID- 17339173 TI - Mucoepidermoid carcinoma on the vermilion border of the upper lip: a case report and literature review. AB - Mucoepidermoid carcinoma occurring in the upper lip is extremely rare. A review of the English literature on mucoepidermoid carcinoma found only four reported cases in the lower lip, and none on the vermilion border of the upper lip. We present a 57-year-old patient who had an asymptomatic lesion on the middle upper lip for 30 years. It had grown progressively and had ulcerated over 1 month ago; the tumor was treated by M-excision. After 17 months of post-therapy, the patient had no local recurrence or distant metastasis. Mucoepidermoid carcinoma is a rare malignancy on the vermilion border of the upper lip with no reported cases to date. The origins of this tumor are not completely understood. Complete resection of the mucoepidermoid carcinoma usually achieves a successful outcome. Although very rare, mucoepidermoid carcinoma should be taken into consideration in the differential diagnosis of any upper lip mass. PMID- 17339174 TI - Seizure after local anesthesia for nasopharyngeal angiofibroma. AB - We report a young male patient who experienced seizure after local injection of 3 mL 2% lidocaine with epinephrine 1:200,000 around a recurrent nasal angiofibroma. After receiving 100% oxygen via mask and thiamylal sodium, the patient had no residual neurologic sequelae. Seizure immediately following the injection of local anesthetics in the nasal cavity is probably due to injection into venous or arterial circulation with retrograde flow to the brain circulation. Further imaging study or angiography should be done before head and neck surgeries, especially in such highly vascular neoplasm. PMID- 17339175 TI - Current treatment of acute promyelocytic leukemia. PMID- 17339176 TI - Investigating people with mucocutaneous bleeding suggestive of primary hemostatic defects: a low likelihood of a definitive diagnosis? PMID- 17339177 TI - The metabolic syndrome and the risk of thrombosis. PMID- 17339178 TI - The characteristics of hematopoietic stem cells from autoimmune-prone mice and the role of neural cell adhesion molecules in abnormal proliferation of these cells in MRL/lpr mice. AB - BACKGROUND AND OBJECTIVES: Using various animal models for autoimmune diseases, we have previously shown that such diseases are stem cell disorders.1 In order to understand how autoimmune diseases develop, we investigated the distinct qualitative differences between hematopoietic stem cells (HSC) from normal and autoimmune-prone mice. DESIGN AND METHODS: We studied the major histocompatibility complex (MHC) restriction between HSC and stromal cells in vitro and in vivo. We also examined the ability of HSC to adhere to a stromal cell line and, using flow cytometry, analyzed the expression of various adhesion molecules in HSC before and after the onset of autoimmune disease. In addition, the effect of antibodies to anti-adhesion molecules on the proliferation of HSC was investigated. RESULTS: The abnormal HSC of MRL/lpr mice showed no MHC restriction (or preference) with stromal cells either in vitro or in vivo, although there was MHC restriction between normal HSC and stromal cells, as we previously reported.2,3 The abnormal HSC of MRL/lpr mice exhibited enhanced adhesion to stromal cells in vitro and expressed a higher amount of adhesion molecules such as neural cell adhesion molecule (NCAM). Interestingly, the proliferation of HSC in MRL/lpr mice was significantly suppressed by anti-NCAM monoclonaal antibodies. INTERPRETATION AND CONCLUSIONS: Abnormal HSC of MRL/lpr mice are more resilient than normal HSC. Furthermore, among various adhesion molecules, only NCAM shows increased expression on HSC of MRL/lpr mice after the onset of autoimmune diseases, and these molecules contribute to the enhanced proliferation capacity of abnormal HSC in MRL/lpr mice. The present findings suggest that there are intrinsic qualitative differences between HSC from normal and autoimmune-prone MRL/lpr mice. PMID- 17339179 TI - The potential effect of gender in combination with common genetic polymorphisms of drug-metabolizing enzymes on the risk of developing acute leukemia. AB - BACKGROUND AND OBJECTIVES: We examined common polymorphisms in the genes for glutathione S-transferase (GST), cytochrome P450 (CYP), quinone oxoreductase (NQO1), methylene tetrahydrofolate reductase (MTHFR), and thymidylate synthetase (TYMS) and the role of gender associated with the susceptibility to de novo acute leukemia (AL). DESIGN AND METHODS: We conducted a case-control study analyzing the prevalence of the polymorphisms CYP1A1*2A, CYP2E1*5B, CYP3A4*1B, del{GSTT1}, del{GSTM1}, NQO1*2, MTHFR C6777, and TYMS 2R/3R in 443 patients with AL [302 with acute myeloblastic leukemia (AML) and 141 with acute lymphoblastic leukemia (ALL)] and 454 control volunteers, using polymerase chain reaction (PCR)-based methods. RESULTS: We found a higher incidence of del{GSTT1} in patients with AML than among controls (25.6% vs. 13.7%, OR=2.2, p<0.001) and a higher incidence of NQO1*2 homozygosity (NQO1*2hom.) in males with the M3 FAB subtype than in control males (8.6% vs. 2.2%, OR=4.9, p=0.02). The del{GSTT1} and NQO1*2hom. polymorphisms increased the risk of ALL (OR=2.2 and 3.0, p=0.001 and 0.003, respectively). The higher risk conferred by NQO1*2hom. and del{GSTT1} mainly affected males (OR=6.1 and 2.4; p=0.002 and 0.005, respectively). INTERPRETATION AND CONCLUSIONS: Males harboring NQO1*2hom. and del{GSTT1} polymorphisms showed a higher risk than females of developing AL. Thus, gender might influence the risk of AL associated with these genetic polymorphisms. PMID- 17339180 TI - Using quantification of the PML-RARalpha transcript to stratify the risk of relapse in patients with acute promyelocytic leukemia. AB - BACKGROUND AND OBJECTIVES: The detection of PML-RARalpha by real-time polymerase chain reaction (RQ-PCR) is becoming an important tool for monitoring minimal residual disease (MRD) in patients with acute promyelocytic leukemia (APL). However, its clinical value remains to be determined. Our aim was to analyze any associations between the risk of relapse and RQ-PCR results in different phases of treatment, comparing these data with those yielded by conventional qualitative reverse transcriptase-PCR. DESIGN AND METHODS: Follow-up samples from 145 APL patients treated with the PETHEMA protocols were evaluated by the RQ-PCR protocol (Europe Against Cancer program) and by the RT-PCR method (BIOMED-1 Concerted Action). Hematologic and molecular relapses and relapse-free survival were recorded. We then looked for associations between relapse risk and RQ-PCR results. RESULTS: After induction therapy, no association was found between positive RQ-PCR results and relapse. The PCR result here did not imply any change in the scheduled therapy. After the third consolidation course, two out of three cases with positive RQ-PCR relapsed in contrast to 16 out of 119 (13%) patients with negative RQ-PCR. During maintenance therapy and out-of treatment, all patients with >10 PML-RARalpha normalized copy number (NCN) (n=19) relapsed while all patients with <1 NCN at the end of the study remained in hematologic remission (p<0.0001). In the intermediate group (NCN 1-10) (n=18), the relapse free survival at 5 years was 60%. Hematologic relapses were predicted if a positive RQ-PCR result had been obtained in a follow-up sample within the previous 4 months. INTERPRETATION AND CONCLUSIONS: Based on the information provided by RQ-PCR in samples obtained after the end of consolidation and subsequently, a relapse risk stratification could be established for APL patients. This stratification divides patients into three groups: those at high risk of relapse, those with an intermediate risk and those with a low risk of relapse. PMID- 17339181 TI - Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells. AB - BACKGROUND AND OBJECTIVES: Stem cells play an important role in the pathogenesis and maintenance of most malignant tumors. Acute myeloid leukemia (AML) is a stem cell disease. The inefficient targeting of the leukemic stem cells (LSC) is considered responsible for relapse after the induction of complete hematologic remission (CR) in AML. Acute promyelocytic leukemia (APL) is a subtype of AML characterized by the t(15;17) translocation and expression of the PML/RARalpha fusion protein. Treatment of APL with all-trans retinoic acid (ATRA) induces CR, but not molecular remission (CMR), because the fusion transcript remains detectable, followed by relapse within a few months. Arsenic induces high rates of CR and CMR followed by a long relapse-free survival (RFS). Here we compared the effects of ATRA and arsenic on PML/RARalpha-positive stem cell compartments. DESIGN AND METHODS: As models for the PML/RARalpha-positive LSC we used: (i) Sca1+/lin- murine HSC retrovirally transduced with PML/RARalpha; (ii) LSC from mice with PML/RARalpha-positive leukemia; (iii) the side population of the APL cell line NB4. RESULTS: In contrast to ATRA, arsenic abolishes the aberrant stem cell capacity of PML/RARalpha-positive stem cells. Arsenic had no apparent influence on the proliferation of PML/RARalpha-positive stem cells, whereas ATRA greatly increased the proliferation of these cells. Furthermore ATRA induces proliferation of APL-derived stem cells, whereas arsenic inhibits their growth. INTERPRETATIONS AND CONCLUSIONS: Taken together our data suggest a relationship between the capacity of a compound to target the leukemia-initiating cell and its ability to induce long relapse-free survival. These data strongly support the importance of efficient LSC-targeting for the outcome of patients with leukemia. PMID- 17339182 TI - Subclassification of patients with acute myelogenous leukemia based on chemokine responsiveness and constitutive chemokine release by their leukemic cells. AB - BACKGROUND AND OBJECTIVES: Chemokines are soluble mediators involved in angiogenesis, cellular growth control and immunomodulation. In the present study we investigated the effects of various chemokines on proliferation of acute myelogenous leukemia (AML) cells and constitutive chemokine release by primary AML cells. DESIGN AND METHODS: Native human AML cells derived from 68 consecutive patients were cultured in vitro. We investigated AML cell proliferation (3H thymidine incorporation, colony formation), chemokine receptor expression, constitutive chemokine release and chemotaxis of normal peripheral blood mononuclear cells. RESULTS: Exogenous chemokines usually did not have any effect on AML blast proliferation in the absence of hematopoietic growth factors, but when investigating growth factor-dependent (interleukin 3 + granulocyte macrophage colony-stimulating factor + stem cell factor) proliferation in suspension cultures the following patient subsets were identified: (i) patients whose cells showed chemokine-induced growth enhancement (8 patients); (ii) divergent effects on proliferation (15 patients); and (iii) no effect (most patients). These patient subsets did not differ in chemokine receptor expression, but, compared to CD34- AML cells, CD34+ cells showed higher expression of several receptors. Chemokines also increased the proliferation of clonogenic AML cells from the first subset of patients. Furthermore, a broad constitutive chemokine release profile was detected for most patients, and the following chemokine clusters could be identified: CCL2-4/CXCL1/8, CCL5/CXCL9-11 (possibly also CCL23) and CCL13/17/22/24/CXCL5 (possibly also CXCL6). Only the CCL2-4/CXCL1/8 cluster showed significant correlations between corresponding mRNA levels and NFkB levels/activation. The chemotaxis of normal immunocompetent cells for patients without constitutive chemokine release was observed to be decreased. INTERPRETATION AND CONCLUSIONS: Differences in chemokine responsiveness as well as chemokine release contribute to patient heterogeneity in AML. Patients with AML can be classified into distinct subsets according to their chemokine responsiveness and chemokine release profile. PMID- 17339183 TI - Absence of prognostic impact of CD13 and/or CD33 antigen expression in adult acute lymphoblastic leukemia. Results of the GIMEMA ALL 0496 trial. AB - BACKGROUND AND OBJECTIVES: The prognostic value of myeloid antigen (MyAg) expression in adult acute lymphoblastic leukemia (ALL) is still controversial. The aim of this study was to correlate the expression of MyAg with clinical, hematologic and biological parameters, and to analyze the impact on response to treatment and prognosis in a large series of adult ALL uniformly characterized and treated. DESIGN AND METHODS: We analyzed the expression of the MyAg CD13 and/or CD33 in a cohort of 377 adult patients with de novo ALL enrolled and treated in the GIMEMA ALL 0496 protocol. RESULTS: MyAg expression was documented in 35% of the 377 adult ALL cases analyzed. MyAg were significantly more frequently associated with B-lineage ALL (38%) than with T-ALL (24%) (p=0.02). No difference was found with regard to clinical features at presentation; a difference was found only for white cell count (p=0.03), percentage of peripheral blasts (p=0.004) and platelet count (p=0.004). No difference was observed in the expression of MyAg between patients with normal or abnormal cytogenetics or between those with high-risk (BCR-ABL+, ALL1-AF4+, E2A-PBX1+) or low-risk B lineage ALL. We failed to observe any difference between MyAg-positive and MyAg negative cases in terms of achievement of complete remission, disease-free survival and overall survival at 5 years. INTERPRETATION AND CONCLUSIONS: Our data indicate that ALL MyAg expression in adults with ALL is not associated with adverse presenting clinical and biological features, and that response to treatment and prognosis is comparable in MyAg-positive and MyAg-negative ALL patients with regards to both complete remission rate and overall survival. We suppose that these result are due to more intensive treatment modalities adopted in the GIMEMA ALL 0496 protocol. PMID- 17339184 TI - The prognostic role of CXCR3 expression by chronic lymphocytic leukemia B cells. AB - BACKGROUND AND OBJECTIVES: Chemokine receptors are involved in tumor progression and several of these receptors, including CXCR3, are expressed by chronic lymphocytic leukemia (CLL) B cells. This study was aimed to examine a possible relationship between CXCR3 expression in CLL and the clinical evolution of the disease. DESIGN AND METHODS: Using flow activated cell sorting (FACS), we analyzed the level of expression of CXCR3 on blood CLL B cells from 76 consecutive patients. The results were correlated with CD38 expression, IgVH gene status and clinical outcome. RESULTS: CXCR3, measured as mean fluorescence intensity (MFI), was unimodally expressed by blood tumor cells at various levels (range, 3.5 to 232.3) but levels within individual patients were remarkably stable over time. Low CXCR3 expression by CLL B cells was strongly associated with Rai disease stages III and IV (p<0.0001) and a pattern of diffuse tumor infiltration of the bone marrow (p<0.0001). In the 28 cases available for genetic studies, low CXCR3 expression also showed good concordance with tumor unmutated IgVH gene status (p<0.04), and tended to correlate with high CD38 expression (p<0.06). Patients with low CXCR3 expression (MFI < or =15) had a shorter survival (p<0.0001) and, in multivariate analysis, low CXCR3 expression (MFI pound15) was an independent predictor of poor outcome (hazard ratio 24.5; p<0.01). INTERPRETATION AND CONCLUSIONSL: CXCR3 expression by CLL B cells appears to be stable within individual patients. Tests to assay this chemokine receptor are cheap and easy to perform and the results could be of prognostic value in CLL. PMID- 17339185 TI - High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls. AB - BACKGROUND AND OBJECTIVES: Mucocutaneous bleeding (MCB) is the main expression of inherited disorders of primary hemostasis. However, the relative prevalence of these disorders, their clinical differential diagnosis, and the proportion of patients with MCB of unknown cause (BUC) after an initial comprehensive laboratory testing are unknown. DESIGN AND METHODS: We studied prospectively 280 consecutive patients with MCB and 299 matched controls, using strict inclusion and exclusion criteria. A single physician recorded the clinical data in a bleeding score and estimated the severity of bleeding in clinical categories. Laboratory criteria for the diagnosis of von Willebrand's disease (VWD) and platelet function defects were established from reference values derived from controls. RESULTS: Fifty patients (17.9%) had VWD (type 1VWD=45, type 2=5). Platelet function defects and mild clotting factor deficiencies were found in 65 (23.2%) and 11 (3.9%) patients, respectively. Thirteen (11.5%) patients had combined defects. The remaining 167(59.6%) patients had BUC, with prolonged bleeding time in 18.6% as their only abnormality. All these disorders, including BUC, were clinically undistinguishable. Moreover, no relationship was found between the severity of bleeding and VWF/platelet function variables. INTERPRETATION AND CONCLUSIONS: The diagnostic efficacy of a first laboratory testing in patients with hereditary MCB is 40.4%. Most patients have a disease(s) of high prevalence but unknown pathogenesis. Concurrent bleeding disorders in the same patient are frequent. Our results support the proposal that low plasma VWF levels, but also platelet function defects, should be considered risk factors rather than unequivocal causes of hemorrhages. PMID- 17339186 TI - Surgical bleeding after pre-operative unfractionated heparin and low molecular weight heparin for coronary bypass surgery. AB - BACKGROUND AND OBJECTIVES: Since the impairment of platelet function may cause excess peri-operative bleeding, pre-operative discontinuation of aspirin and heparin bridging are common for cardiac surgery. We evaluated the impact of pre operative administration of enoxaparin and unfractionated heparin (UFH) on coagulation parameters and peri-operative bleeding in patients undergoing elective coronary artery bypass grafting (CABG) surgery after discontinuation of aspirin. DESIGN AND METHODS: Forty-three patients with three-vessel coronary artery disease undergoing elective CABG surgery discontinued aspirin and were randomized to receive either UFH 180 UI/Kg x 2/day s.c. or enoxaparin 100 UI/Kg x 2/day s.c. until 12 h before surgery (median pre-operative treatment 8 days, range 6-12 days). Surgery was performed as usual with UFH. Neither UFH nor any low molecular weight heparin was given in the immediate post-operative period. The effects of UFH and enoxaparin were monitored by the activated partial thromboplastin time (aPTT) and the Enox-test (sensitive to factor Xa inhibition) using a Rapidpoint Coagulation Analyzer. aPTT and factor Xa activity were also measured by standard methods. Peri-operative bleeding and the nadirs of hemoglobin concentration, hematocrit and platelet count were monitored post operatively. RESULTS: Patients in the two groups were similar for number of bypasses, on-pump time, total surgery time, and time from the last heparin administration. Coagulation parameters increased significantly and similarly at 30 min and 6 h with both treatments, but returned within the normal range at 12 h. Hemoglobin, hematocrit and platelet counts significantly decreased to the same extent after CABG and re-normalized at the same time. Transfusional requirements of blood and plasma units were similar in the two groups. INTERPRETATION AND CONCLUSIONS: From the kinetics of coagulation parameters and the evaluation of bleeding, enoxaparin is a safe alternative to UFH as a bridging therapy to CABG after discontinuation of aspirin. PMID- 17339187 TI - Venous thromboembolism--a manifestation of the metabolic syndrome. AB - BACKGROUND AND OBJECTIVES: The metabolic syndrome, defined by abdominal obesity, elevation of blood pressure, fasting glucose and triglycerides and low levels of high-density lipoprotein cholesterol is associated with atherosclerotic disease. It induces a pro-inflammatory and prothrombotic state. Despite its high prevalence, data on the association with venous thromboembolism (VTE) are scarce. The aim of our study was to elucidate the association of the metabolic syndrome with the risk of VTE. DESIGN AND METHODS: We conducted a case-control study to investigate the presence of the metabolic syndrome defined according to guidelines of the National Cholesterol Education Program, in high-risk patients with objectively confirmed recurrent VTE, who had had at least one unprovoked event of deep venous thrombosis or pulmonary embolism. Age and sex-matched healthy individuals served as controls. RESULTS: A total of 116 patients and 129 controls were enrolled. The prevalence of the metabolic syndrome was statistically significantly higher in patients (40/116, 35%) than in controls (26/129, 20%, p=0.012). The unadjusted odds ratio (OR) of the metabolic syndrome for VTE was 2.1 (95% CI [1.2-3.7], p=0.012) and remained statistically significant after adjustment for established thrombosis risk factors, sex and age (OR=2.2, 95% CI [1.1-4.3], p=0.020). Individuals with the metabolic syndrome (n=66) had significantly higher levels of high-sensitivity C-reactive protein (median, [interquartile range]: 0.312 mg/dL, [0.142-0.751] vs. 0.153 mg/dL, [0.073-0.330], p<0.001), fibrinogen (390 mg/dL, [342-432] vs. 343 mg/dL, [310 394], p<0.001) and factor VIII activity (182%, [157-216] vs. 159%, [133-199], p=0.005) compared to those without (n=179). INTERPRETATION AND CONCLUSIONS: The metabolic syndrome may contribute to the development of VTE and is associated with a two-fold increased risk of VTE. PMID- 17339188 TI - Chimeric T-cell receptors: new challenges for targeted immunotherapy in hematologic malignancies. AB - Chimeric T-cell receptors (ChTCR), are a fascinating technological step in the field of immunotherapy for orienting the activity of immune cells towards specific molecular targets expressed on the cell surface of various tumors, including hematologic malignancies. The main characteristics of ChTCR are their ability to redirect T-cell specificity and their killing/effector activity toward a selected target in a non MHC-restricted manner, exploiting the antigen binding properties of monoclonal antibodies. ChTCR are, in fact, artificial T-cell receptors constituted by an antigen-recognizing antibody molecule linked to a T cell triggering domain. Various hematologic malignancies represent optimal targets for the exploitation of ChTCR, because of the bright expression of specific antigens on the surface of tumor cells. Thus, CD19 and CD20 have been targeted for B-cell lymphoid tumors (acute lymphoblastic leukemia-ALL, lymphomas and chronic lymphocytic leukemia-CLL), CD33 for myeloid leukemia, and CD30 for lymphomas. Even though technical and safety progresses are still needed to improve the profile of gene transfer and protein expression of ChTCR, phase 1 trials will be carried out in the near future to demonstrate the feasibility of their clinical translation and, it is be hoped, give preliminary indications about their anti-tumor efficacy. PMID- 17339189 TI - Autologous stem cell transplantation after complete remission and first consolidation in acute myeloid leukemia patients aged 61-70 years: results of the prospective EORTC-GIMEMA AML-13 study. AB - BACKGROUND AND OBJECTIVES: The optimal post-remission treatment for elderly patients with acute myeloid leukemia (AML) is presently unknown. Recent studies have reported the feasibility of autologous peripheral blood stem cell transplantation (PBSCT) in this population. We evaluate the outcome of this post remission approach after complete remission (CR) and consolidation in elderly patients included in the EORTC-GIMEMA AML-13 trial. DESIGN AND METHODS: PBSCT after induction and consolidation chemotherapy was evaluated in patients aged 61 to 70 years with a WHO performance status 0-1. The induction therapy was mitoxantrone, etoposide and cytarabine (MICE) with or without granulocyte colony stimulating factor (G-CSF) during and/or after chemotherapy. The consolidation therapy consisted of non-infusion or infusional idarubicin, etposide and cytarabine (mini-ICE). RESULTS: Sixty-one patients were scheduled for stem cell harvest by leukapheresis after s.c. recombinant human G-CSF administration initiated after hematopoietic recovery from consolidation. Stem cells were effectively harvested from 54 patients. A median of two aphereses (range, 1-5) were performed, resulting in a median collection of 11.7 x 10(8) nucleated cells/kg (range, 2.4-99.8) containing 40.2 x 10(4) CFU-GM/kg (range, 0-786.8), and 5 x 10(6) CD34+ cells/kg (range, 0.1-99.8). For the whole group of 61 patients, the median disease-free survival (DFS) was 1.0 years and the 3-year DFS rate was 21%, while the median overall survival (OS) was 1.4 years and the 3-year OS rate was 32%. A total of 26 patients could not be autografed due to inadequate/no harvest (21 patients), early relapse (3 patients), or treatment refusal (2 patients). Autologous transplantation was performed in 35 patients following conditioning with the BAVC regimen. The median time for granulocyte recovery >0.5 109 yen/L was 24 days and for platelets >20 x10(9)/L was 23 days following transplantation. After a median follow-up of 5.0 years from transplantation, the median DFS and OS were 1.1 and 1.6 years respectively, and the 3-year rates were 28% and 39% respectively. Eight autografted patients were still in continuous complete remission, 22 patients had relapsed and five had died in CR. INTERPRETATION AND CONCLUSIONS: Intensification of remission including autologous PBSCT is feasible in about half of harvested patients aged 61 to 70 years old, and did not improve the general outcome. This shows the limitations of autologous PBSCT and other intensive treatment modalities in elderly AML patients. Key words: acute myeloid leukemia, elderly, autologous stem cell transplantation. PMID- 17339190 TI - Immunosuppressive therapy with anti-thymocyte globulin and cyclosporine A in selected children with hypoplastic refractory cytopenia. AB - It is currently unknown whether immunosuppressive therapy or hematopoietic stem cell transplantation is the most appropriate treatment strategy for children with refractory cytopenia and normal karyotype or trisomy 8. We report on 31 children with hypoplastic refractory cytopenia treated with immunosuppressive therapy consisting of antithymocyte globulin and cyclosporine. At 6 months, 22 of 29 evaluable patients had a complete or partial response; a total of ten patients achieved a complete response at varying time points. Six patients subsequently received a transplant because of non-response, progression to advanced myelodysplastic syndrome or evolution of monosomy 7. Overall and failure-free survival rates at 3 years were 88% and 57%, respectively. PMID- 17339191 TI - Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain. AB - The emergence of resistance to the Bcr-Abl inhibitor imatinib mesylate in patients with Philadelphia chromosome-positive (Ph+) leukemia has prompted the development of second-generation compounds active against several imatinib insensitive mutant forms of Bcr-Abl, including dasatinib (BMS-354825; Bristol Myers Squibb). In order to assess which pre-existent or emerging kinase domain mutations are associated with decreased clinical efficacy of desatinib, we analyzed BCR-ABL kinase sequences before and during treatment in 21 Ph+ patients who failed to respond to or relapsed during dasatinib therapy. In all patients but one, resistance to dasatinib was invariably found to be associated with mutations at residue 315 and/or at residue 317. PMID- 17339192 TI - The translocations t(6;18;11)(q24;q21;q21) and t(11;14;18)(q21;q32;q21) lead to a fusion of the API2 and MALT1 genes and occur in MALT lymphomas. AB - So far, only one variant translocation of the t(11;18)(q21;q21), the t(11;12;18) (q21;q13;q21), has been reported. We herein describe two new variant translocations, the t(6;18;11)(q24;q21;q21) and the t(11;14;18)(q21;q32;q21), occurring in mucosa-associated lymphoid tissue (MALT) lymphomas. In both cases, fluorescence in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR) revealed the presence of an 5'API2-3'MALT1 fusion product, encoded on the derivative chromosome 11. Exon 7 of API2 was fused with exon 5 of MALT1 in the t(11;14;18) and with exon 8 of MALT1 in the t(6;18;11). FISH revealed the involvement of the immunoglobulin locus in the t(11;14;18). Rapid amplification of cDNA ends (RACE)-PCR to detect the involved partner gene on 6q showed exclusively wild-type API2 and MALT1 sequences. PMID- 17339193 TI - Deferral of assessment of pulmonary embolism. AB - We evaluated a simplified algorithm for safely postponing diagnostic imaging for pulmonary embolism (PE). At the index visit, patients were identified as being at high or low risk of PE; the former received full dosage low molecular weight heparin while the latter were left untreated until performance of diagnostic imaging (max 72 hours). During this period, no thromboembolic events occurred in low-risk patients (0/211, 0.% [upper 95% CI 0.9%]); only one event occurred in those at high-risk (1/125, 0.8% [upper 95% CI, 1.2]). Our study demonstrates that diagnostic imaging for PE can be safely deferred for up to 3 days. PMID- 17339194 TI - Donor lymphocyte infusion for the treatment of leukemia relapse after HLA mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation. AB - In this study, we tested the efficacy and safety of donor lymphocyte infusion (DLI) with granulocyte colony-stimulating factor (G-CSF) priming in patients who relapsed after haploidentical hematopoietic stem cell transplantation (HSCT). Twenty patients received DLI at a median of 177 days after HSCT. Eight patients survived in complete remission for a median of 1118 days. The 2-year probability of leukemia-free survival was 40%. Acute graft-versus-host disease (GVHD) grade 3 4 occurred in six patients after DLI. GVHD prophylaxis reduced the incidence of acute GVHD. Our primary data showed that G-CSF-primed DLI with GVHD prophylaxis was a potentially effective therapeutic option for patients who relapsed after haploidentical HSCT. PMID- 17339195 TI - Reduced intensity stem cell transplantation for advanced soft tissue sarcomas in adults: a retrospective analysis of the European Group for Blood and Marrow Transplantation. AB - We conducted a retrospective analysis on adult patients with advanced soft tissue sarcoma (STS) other than rhabdomyosarcoma who received allogeneic stem cell transplantation and were registered at the EBMT database. The aim of of the study was to assess whether an immune-mediated graft-versus-tumor (GVT) effect could be generated in this disease. Among 26 patients included in the registry, 14 were eligible for this analysis as they had received reduced intensity stem cell transplantation for chemorefractory disease. Two patients died of transplant related complications and eight of progressive disease; four are alive and experienced long-lasting disease stabilisation following transplant. Our study may suggest that an immune-mediated effect cannot be excluded in some STS. PMID- 17339196 TI - Juvenile hemochromatosis caused by a novel combination of hemojuvelin G320V/R176C mutations in a 5-year old girl. AB - During a screening program we identified a 5-year old girl with elevated iron parameters. The child was found to have a combination of a novel R176C mutation together with the G320V mutation in the juvenile hemochromatosis gene (HJV). The girl was also homozygous for the H63D mutation in HFE. The possibility of detecting juvenile hemochromatosis before the onset of clinical manifestations raises questions about the management of such young children in order to prevent iron overload. PMID- 17339197 TI - A 65 bp duplication/insertion in exon II of the beta globin gene causing beta0 thalassemia. AB - We describe a patient originating from Ghana who had combined heterozygous alpha (4.2)thalassemia, alpha alpha alpha anti3.7 triplication, the common delta globin variant HbA2' and a new 65 bp duplication/insertion in exon II of the b globin gene causing beta (0)-thalassemia. PMID- 17339198 TI - Steroid treatment in children with sickle-cell disease. AB - Given the controversy concerning the effects of steroids in patients with sickle cell disease (SCD), we evaluated the tolerability of long-term steroid treatment in 16 children with SCD and autoimmune and/or systemic diseases. The steroid treatment was poorly tolerated. PMID- 17339199 TI - Abnormalities of erythrocyte glycoconjugates are identical in two families with congenital dyserythropoietic anemia type II with different chromosomal localizations of the disease gene. AB - We analyzed erythrocyte glycoconjugates in two families with congenital dyserythropoietic anemia type II (CDA-II): family 2 with the typical localization of the disease gene to chromosome 20q11.2 and family 1 in which this localization was excluded. Despite the different genetics, the erythrocyte glycoconjugate abnormalities in the two families were identical suggesting a complex inheritance of CDA-II. We also found that erythrocyte anion exchanger 1 protein is decreased in CDA-II homozygotes and obligate carriers alike. PMID- 17339200 TI - Monitoring BCR-ABL transcript levels by real-time quantitative polymerase chain reaction: a linear regression equation to convert from BCR-ABL/B2M ratio to estimated BCR-ABL/ABL ratio. AB - In order to overcome the problem of different control genes for BCR-ABL normalization, we used a linear regression equation to compare our results previously obtained using B2M as the control gene with those calculated using the ABL gene and validated the slope as a factor to convert from B2M to ABL results. PMID- 17339201 TI - JAK2V617F detection and dosage of serum erythropoietin: first steps of the diagnostic work-up for patients consulting for elevated hematocrit. AB - The predictive values of common biological criteria for the diagnosis of polycythemia vera were studied in a cohort of patients with high hematocrit. We found JAK2V617F and erythropoietin assays were the most relevant first tests. Classification of patients according to their JAK2V617F status and erythropoietin levels facilitated the choice of further diagnostic investigations. PMID- 17339202 TI - Quantitative trait loci associated with photoperiodic response and stage of diapause in the pitcher-plant mosquito, Wyeomyia smithii. AB - A wide variety of temperate animals rely on length of day (photoperiodism) to anticipate and prepare for changing seasons by regulating the timing of development, reproduction, dormancy, and migration. Although the molecular basis of circadian rhythms regulating daily activities is well defined, the molecular basis for the photoperiodic regulation of seasonal activities is largely unknown. We use geographic variation in the photoperiodic control of diapause in the pitcher-plant mosquito Wyeomyia smithii to create the first QTL map of photoperiodism in any animal. For critical photoperiod (CPP), we detect QTL that are unique, a QTL that is sex linked, QTL that overlap with QTL for stage of diapause (SOD), and a QTL that interacts epistatically with the circadian rhythm gene, timeless. Results presented here confirm earlier studies concluding that CPP is under directional selection over the climatic gradient of North America and that the evolution of CPP is genetically correlated with SOD. Despite epistasis between timeless and a QTL for CPP, timeless is not located within any detectable QTL, indicating that it plays an ancillary role in the evolution of photoperiodism in W. smithii. Finally, we highlight one region of the genome that includes loci contributing to CPP, SOD, and hormonal regulation of development. PMID- 17339203 TI - Precise mapping of quantitative trait loci for resistance to southern leaf blight, caused by Cochliobolus heterostrophus race O, and flowering time using advanced intercross maize lines. AB - The intermated B73 x Mo17 (IBM) population, an advanced intercross recombinant inbred line population derived from a cross between the maize lines B73 (susceptible) and Mo17 (resistant), was evaluated in four environments for resistance to southern leaf blight (SLB) disease caused by Cochliobolus heterostrophus race O. Two environments were artificially inoculated, while two were not inoculated and consequently had substantially lower disease pressure. Four common SLB resistance quantitative trait loci (QTL) were identified in all environments, two in bin 3.04 and one each in bins 1.10 and 8.02/3. There was no significant correlation between disease resistance and days to anthesis. A direct comparison was made between SLB QTL detected in two populations, independently derived from the same parental cross: the IBM advanced intercross population and a conventional recombinant inbred line population. Several QTL for SLB resistance were detected in both populations, with the IBM providing between 5 and, in one case, 50 times greater mapping resolution. PMID- 17339204 TI - Caenorhabditis elegans mutants resistant to attachment of Yersinia biofilms. AB - The detailed composition and structure of the Caenorhabditis elegans surface are unknown. Previous genetic studies used antibody or lectin binding to identify srf genes that play roles in surface determination. Infection by Microbacterium nematophilum identified bus (bacterially unswollen) genes that also affect surface characteristics. We report that biofilms produced by Yersinia pestis and Y. pseudotuberculosis, which bind the C. elegans surface predominantly on the head, can be used to identify additional surface-determining genes. A screen for C. elegans mutants with a biofilm absent on the head (Bah) phenotype identified three novel genes: bah-1, bah-2, and bah-3. The bah-1 and bah-2 mutants have slightly fragile cuticles but are neither Srf nor Bus, suggesting that they are specific for surface components involved in biofilm attachment. A bah-3 mutant has normal cuticle integrity, but shows a stage-specific Srf phenotype. The screen produced alleles of five known surface genes: srf-2, srf-3, bus-4, bus-12, and bus-17. For the X-linked bus-17, a paternal effect was observed in biofilm assays. PMID- 17339205 TI - Genetic similarities within and between human populations. AB - The proportion of human genetic variation due to differences between populations is modest, and individuals from different populations can be genetically more similar than individuals from the same population. Yet sufficient genetic data can permit accurate classification of individuals into populations. Both findings can be obtained from the same data set, using the same number of polymorphic loci. This article explains why. Our analysis focuses on the frequency, omega, with which a pair of random individuals from two different populations is genetically more similar than a pair of individuals randomly selected from any single population. We compare omega to the error rates of several classification methods, using data sets that vary in number of loci, average allele frequency, populations sampled, and polymorphism ascertainment strategy. We demonstrate that classification methods achieve higher discriminatory power than omega because of their use of aggregate properties of populations. The number of loci analyzed is the most critical variable: with 100 polymorphisms, accurate classification is possible, but omega remains sizable, even when using populations as distinct as sub-Saharan Africans and Europeans. Phenotypes controlled by a dozen or fewer loci can therefore be expected to show substantial overlap between human populations. This provides empirical justification for caution when using population labels in biomedical settings, with broad implications for personalized medicine, pharmacogenetics, and the meaning of race. PMID- 17339206 TI - Experimental estimate of the abundance and effects of nearly neutral mutations in the RNA virus phi 6. AB - Although the frequency and effects of neutral and nearly neutral mutations are critical to evolutionary patterns and processes governed by genetic drift, the small effects of such mutations make them difficult to study empirically. Here we present the results of a mutation-accumulation experiment designed to assess the frequencies of deleterious mutations with undetectable effects. We promoted the accumulation of spontaneous mutations by subjecting independent lineages of the RNA virus 6 to repeated population bottlenecks of a single individual. We measured fitness following every bottleneck to obtain a complete picture of the timing and effects of the accumulated mutations with detectable effects and sequenced complete genomes to determine the number of mutations that were undetected by the fitness assays. To estimate the effects of the undetected mutations, we implemented a likelihood model developed for quantitative trait locus (QTL) data (Otto and Jones 2000) to estimate the number and effects of the undetected mutations from the measured number and effects of the detected mutations. Using this method we estimated a deleterious mutation rate of U = 0.03 and a gamma effects distribution with mean s=0.093 and coefficient of variation = 0.204. Although our estimates of U and s fall within the range of recent mutation rate and effect estimates in eukaryotes, the fraction of mutations with detectable effects on laboratory fitness (39%) appears to be far higher in 6 than in eukaryotes. PMID- 17339207 TI - Under neutrality, Q(ST) < or = F(ST) when there is dominance in an island model. PMID- 17339208 TI - Natural selection on fecundity variance in subdivided populations: kin selection meets bet hedging. AB - In a series of seminal articles in 1974, 1975, and 1977, J. H. Gillespie challenged the notion that the "fittest" individuals are those that produce on average the highest number of offspring. He showed that in small populations, the variance in fecundity can determine fitness as much as mean fecundity. One likely reason why Gillespie's concept of within-generation bet hedging has been largely ignored is the general consensus that natural populations are of large size. As a consequence, essentially no work has investigated the role of the fecundity variance on the evolutionary stable state of life-history strategies. While typically large, natural populations also tend to be subdivided in local demes connected by migration. Here, we integrate Gillespie's measure of selection for within-generation bet hedging into the inclusive fitness and game theoretic measure of selection for structured populations. The resulting framework demonstrates that selection against high variance in offspring number is a potent force in large, but structured populations. More generally, the results highlight that variance in offspring number will directly affect various life-history strategies, especially those involving kin interaction. The selective pressures on three key traits are directly investigated here, namely within-generation bet hedging, helping behaviors, and the evolutionary stable dispersal rate. The evolutionary dynamics of all three traits are markedly affected by variance in offspring number, although to a different extent and under different demographic conditions. PMID- 17339209 TI - Specific defects in different transcription complexes compensate for the requirement of the negative cofactor 2 repressor in Saccharomyces cerevisiae. AB - Negative cofactor 2 (NC2) has been described as an essential and evolutionarily conserved transcriptional repressor, although in vitro and in vivo experiments suggest that it can function as both a positive and a negative effector of transcription. NC2 operates by interacting with the core promoter and components of the basal transcription machinery, like the TATA-binding protein (TBP). In this work, we have isolated mutants that suppress the growth defect caused by the depletion of NC2. We have identified mutations affecting components of three different complexes involved in the control of basal transcription: the mediator, TFIIH, and RNA pol II itself. Mutations in RNA pol II include both overexpression of truncated forms of the two largest subunits (Rpb1 and Rpb2) and reduced levels of these proteins. Suppression of NC2 depletion was also observed by reducing the amounts of the mediator essential components Nut2 and Med7, as well as by deleting any of the nonessential mediator components, except Med2, Med3, and Gal11 subunits. Interestingly, the Med2/Med3/Gal11 triad forms a submodule within the mediator tail. Our results support the existence of different components within the basic transcription complexes that antagonistically interact with the NC2 repressor and suggest that the correct balance between the activities of specific positive and negative components is essential for cell growth. PMID- 17339210 TI - Mapping quantitative trait loci for expression abundance. AB - Mendelian loci that control the expression levels of transcripts are called expression quantitative trait loci (eQTL). When mapping eQTL, we often deal with thousands of expression traits simultaneously, which complicates the statistical model and data analysis. Two simple approaches may be taken in eQTL analysis: (1) individual transcript analysis in which a single expression trait is mapped at a time and the entire eQTL mapping involves separate analysis of thousands of traits and (2) individual marker analysis where differentially expressed transcripts are detected on the basis of their association with the segregation pattern of an individual marker and the entire analysis requires scanning markers of the entire genome. Neither approach is optimal because data are not analyzed jointly. We develop a Bayesian clustering method that analyzes all expressed transcripts and markers jointly in a single model. A transcript may be simultaneously associated with multiple markers. Additionally, a marker may simultaneously alter the expression of multiple transcripts. This is a model based method that combines a Gaussian mixture of expression data with segregation of multiple linked marker loci. Parameter estimation for each variable is obtained via the posterior mean drawn from a Markov chain Monte Carlo sample. The method allows a regular quantitative trait to be included as an expression trait and subject to the same clustering assignment. If an expression trait links to a locus where a quantitative trait also links, the expressed transcript is considered to be associated with the quantitative trait. The method is applied to a microarray experiment with 60 F(2) mice measured for 25 different obesity related quantitative traits. In the experiment, approximately 40,000 transcripts and 145 codominant markers are investigated for their associations. A program written in SAS/IML is available from the authors on request. PMID- 17339211 TI - Classical genetic and quantitative trait loci analyses of heterosis in a maize hybrid between two elite inbred lines. AB - The exploitation of heterosis is one of the most outstanding advancements in plant breeding, although its genetic basis is not well understood yet. This research was conducted on the materials arising from the maize single cross B73 x H99 to study heterosis by procedures of classical genetic and quantitative trait loci (QTL) analyses. Materials were the basic generations, the derived 142 recombinant inbred lines (RILs), and the three testcross populations obtained by crossing the 142 RILs to each parent and their F(1). For seedling weight (SW), number of kernels per plant (NK), and grain yield (GY), heterosis was >100% and the average degree of dominance was >1. Epistasis was significant for SW and NK but not for GY. Several QTL were identified and in most cases they were in the additive-dominance range for traits with low heterosis and mostly in the dominance-overdominance range for plant height (PH), SW, NK, and GY. Only a few QTL with digenic epistasis were identified. The importance of dominance effects was confirmed by highly significant correlations between heterozygosity level and phenotypic performance, especially for GY. Some chromosome regions presented overlaps of overdominant QTL for SW, PH, NK, and GY, suggesting pleiotropic effects on overall plant vigor. PMID- 17339212 TI - A maximum-likelihood method for the estimation of pairwise relatedness in structured populations. AB - A maximum-likelihood estimator for pairwise relatedness is presented for the situation in which the individuals under consideration come from a large outbred subpopulation of the population for which allele frequencies are known. We demonstrate via simulations that a variety of commonly used estimators that do not take this kind of misspecification of allele frequencies into account will systematically overestimate the degree of relatedness between two individuals from a subpopulation. A maximum-likelihood estimator that includes F(ST) as a parameter is introduced with the goal of producing the relatedness estimates that would have been obtained if the subpopulation allele frequencies had been known. This estimator is shown to work quite well, even when the value of F(ST) is misspecified. Bootstrap confidence intervals are also examined and shown to exhibit close to nominal coverage when F(ST) is correctly specified. PMID- 17339213 TI - The effect of dominance on the use of the QST - FST contrast to detect natural selection on quantitative traits. PMID- 17339215 TI - Differential epigenetic regulation within an Arabidopsis retroposon family. AB - We previously reported a novel family of Arabidopsis thaliana nonautonomous retroposons, Sadhu, showing epigenetic variation in natural populations. Here, we show that transcripts corresponding to Sadhu elements accumulate in a subset of mutants carrying disruptions in genes encoding chromatin modification enzymes, but are not significantly expressed in mutants defective in RNA silencing pathways, indicating that RNA-directed processes are not necessary to maintain transcriptional suppression of this class of retroelements. We focused our analysis on three representative elements showing differential responses to ddm1, met1, and hda6 mutations. These mutations had differing effects on cytosine methylation depending on the element and the sequence context. Curiously, the Sadhu6-1 element with the strongest CpHpG methylation is expressed in a met1 CpG methyltransferase mutant, but is not expressed in ddm1 or cmt3 mutants. Regardless of the mutant background, H3meK9 was found at silenced loci, while H3meK4 was restricted to expressed alleles. We discuss the different modes of regulation within this family and the potential impact of this regulation on the stability of silencing in natural populations. PMID- 17339216 TI - Transcriptional control of gluconeogenesis in Aspergillus nidulans. AB - Aspergillus nidulans can utilize carbon sources that result in the production of TCA cycle intermediates, thereby requiring gluconeogenesis. We have cloned the acuG gene encoding fructose-1,6 bisphosphatase and found that expression of this gene is regulated by carbon catabolite repression as well as by induction by a TCA cycle intermediate similar to the induction of the previously studied acuF gene encoding phosphoenolpyruvate carboxykinase. The acuN356 mutation results in loss of growth on gluconeogenic carbon sources. Cloning of acuN has shown that it encodes enolase, an enzyme involved in both glycolysis and gluconeogenesis. The acuN356 mutation is a translocation with a breakpoint in the 5' untranslated region resulting in loss of expression in response to gluconeogenic but not glycolytic carbon sources. Mutations in the acuK and acuM genes affect growth on carbon sources requiring gluconeogenesis and result in loss of induction of the acuF, acuN, and acuG genes by sources of TCA cycle intermediates. Isolation and sequencing of these genes has shown that they encode proteins with similar but distinct Zn(2) Cys(6) DNA-binding domains, suggesting a direct role in transcriptional control of gluconeogenic genes. These genes are conserved in other filamentous ascomycetes, indicating their significance for the regulation of carbon source utilization. PMID- 17339217 TI - Genetic positioning of centromeres using half-tetrad analysis in a 4x-2x cross population of potato. AB - From biological and genetic standpoints, centromeres play an important role in the delivery of the chromosome complement to the daughter cells at cell division. The positions of the centromeres of potato were determined by half-tetrad analysis in a 4x-2x population where the male parent produced 2n pollen by first division restitution (FDR). The genetic linkage groups and locations of 95 male parent-derived amplified fragment length polymorphism markers could be determined by comparing their position on a 2x-2x highly saturated linkage map of potato. Ten centromere positions were identified by 100% heterozygosity transmitted from the 2n heterozygous gametes of the paternal parent into the tetraploid offspring. The position of these centromeric marker loci was in accordance with those predicted by the saturated 2x-2x map using the level of marker clustering as a criterion. Two remaining centromere positions could be determined by extrapolation. The frequent observation of transmission of 100% heterozygosity proves that the meiotic restitution mechanism is exclusively based on FDR. Additional investigations on the position of recombination events of three chromosomes with sufficient numbers of markers showed that only one crossover occurred per chromosome arm, proving strong interference of recombination between centromere and telomere. PMID- 17339218 TI - A soybean transcript map: gene distribution, haplotype and single-nucleotide polymorphism analysis. AB - The first genetic transcript map of the soybean genome was created by mapping one SNP in each of 1141 genes in one or more of three recombinant inbred line mapping populations, thus providing a picture of the distribution of genic sequences across the mapped portion of the genome. Single-nucleotide polymorphisms (SNPs) were discovered via the resequencing of sequence-tagged sites (STSs) developed from expressed sequence tag (EST) sequence. From an initial set of 9459 polymerase chain reaction primer sets designed to a diverse set of genes, 4240 STSs were amplified and sequenced in each of six diverse soybean genotypes. In the resulting 2.44 Mbp of aligned sequence, a total of 5551 SNPs were discovered, including 4712 single-base changes and 839 indels for an average nucleotide diversity of Theta= 0.000997. The analysis of the observed genetic distances between adjacent genes vs. the theoretical distribution based upon the assumption of a random distribution of genes across the 20 soybean linkage groups clearly indicated that genes were clustered. Of the 1141 genes, 291 mapped to 72 of the 112 gaps of 5-10 cM in the preexisting simple sequence repeat (SSR)-based map, while 111 genes mapped in 19 of the 26 gaps >10 cM. The addition of 1141 sequence based genic markers to the soybean genome map will provide an important resource to soybean geneticists for quantitative trait locus discovery and map-based cloning, as well as to soybean breeders who increasingly depend upon marker assisted selection in cultivar improvement. PMID- 17339219 TI - Heteroduplex DNA in meiotic recombination in Drosophila mei-9 mutants. AB - Meiotic recombination gives rise to crossovers, which are required in most organisms for the faithful segregation of homologous chromosomes during meiotic cell division. Characterization of crossover-defective mutants has contributed much to our understanding of the molecular mechanism of crossover formation. We report here a molecular analysis of recombination in a Drosophila melanogaster crossover-defective mutant, mei-9. In the absence of mei-9 activity, postmeiotic segregation associated with noncrossovers occurs at the expense of crossover products, suggesting that the underlying meiotic function for MEI-9 is in crossover formation rather than mismatch repair. In support of this, analysis of the arrangement of heteroduplex DNA in the postmeiotic segregation products reveals different patterns from those observed in Drosophila Msh6 mutants, which are mismatch-repair defective. This analysis also provides evidence that the double-strand break repair model applies to meiotic recombination in Drosophila. Our results support a model in which MEI-9 nicks Holliday junctions to generate crossovers during meiotic recombination, and, in the absence of MEI-9 activity, the double Holliday junction intermediate instead undergoes dissolution to generate noncrossover products in which heteroduplex is unrepaired. PMID- 17339220 TI - Meiotic recombination in Drosophila Msh6 mutants yields discontinuous gene conversion tracts. AB - Crossovers (COs) generated through meiotic recombination are important for the correct segregation of homologous chromosomes during meiosis. Several models describing the molecular mechanism of meiotic recombination have been proposed. These models differ in the arrangement of heteroduplex DNA (hDNA) in recombination intermediates. Heterologies in hDNA are usually repaired prior to the recovery of recombination products, thereby obscuring information about the arrangement of hDNA. To examine hDNA in meiotic recombination in Drosophila melanogaster, we sought to block hDNA repair by conducting recombination assays in a mutant defective in mismatch repair (MMR). We generated mutations in the MMR gene Msh6 and analyzed recombination between highly polymorphic homologous chromosomes. We found that hDNA often goes unrepaired during meiotic recombination in an Msh6 mutant, leading to high levels of postmeiotic segregation; however, hDNA and gene conversion tracts are frequently discontinuous, with multiple transitions between gene conversion, restoration, and unrepaired hDNA. We suggest that these discontinuities reflect the activity of a short-patch repair system that operates when canonical MMR is defective. PMID- 17339221 TI - The Caenorhabditis elegans Rad17 homolog HPR-17 is required for telomere replication. AB - Subunits of the Rad9/Rad1/Hus1 (9-1-1) proliferating cell nuclear antigen (PNCA) like sliding clamp are required for DNA damage responses and telomerase-mediated telomere replication in the nematode Caenorhabditis elegans. PCNA sliding clamps are loaded onto DNA by a replication factor C (RFC) clamp loader. The C. elegans Rad17 RFC clamp loader homolog, hpr-17, functions in the same pathway as the 9-1 1 complex with regard to both the DNA damage response and telomerase-mediated telomere elongation. Thus, hpr-17 defines an RFC-like complex that facilitates telomerase activity in vivo in C. elegans. PMID- 17339222 TI - Adaptive divergence in experimental populations of Pseudomonas fluorescens. III. Mutational origins of wrinkly spreader diversity. AB - Understanding the connections among genotype, phenotype, and fitness through evolutionary time is a central goal of evolutionary genetics. Wrinkly spreader (WS) genotypes evolve repeatedly in model Pseudomonas populations and show substantial morphological and fitness differences. Previous work identified genes contributing to the evolutionary success of WS, in particular the di-guanylate cyclase response regulator, WspR. Here we scrutinize the Wsp signal transduction pathway of which WspR is the primary output component. The pathway has the hallmarks of a chemosensory pathway and genetic analyses show that regulation and function of Wsp is analogous to the Che chemotaxis pathway from Escherichia coli. Of significance is the methyltransferase (WspC) and methylesterase (WspF) whose opposing activities form an integral feedback loop that controls the activity of the kinase (WspE). Deductions based on the regulatory model suggested that mutations within wspF were a likely cause of WS. Analyses of independent WS genotypes revealed numerous simple mutations in this single open reading frame. Remarkably, different mutations have different phenotypic and fitness effects. We suggest that the negative feedback loop inherent in Wsp regulation allows the pathway to be tuned by mutation in a rheostat-like manner. PMID- 17339223 TI - Proofreading and secondary structure processing determine the orientation dependence of CAG x CTG trinucleotide repeat instability in Escherichia coli. AB - Expanded CAG x CTG trinucleotide repeat tracts are associated with several human inherited diseases, including Huntington's disease, myotonic dystrophy, and spinocerebellar ataxias. Here we describe a new model system to investigate repeat instability in the Escherichia coli chromosome. Using this system, we reveal patterns of deletion instability consistent with secondary structure formation in vivo and address the molecular basis of orientation-dependent instability. We demonstrate that the orientation dependence of CAG x CTG trinucleotide repeat deletion is determined by the proofreading subunit of DNA polymerase III (DnaQ) in the presence of the hairpin nuclease SbcCD (Rad50/Mre11). Our results suggest that, although initiation of slippage can occur independently of CAG x CTG orientation, the folding of the intermediate affects its processing and this results in orientation dependence. We propose that proofreading is inefficient on the CTG-containing strand because of its ability to misfold and that SbcCD contributes to processing in a manner that is dependent on proofreading and repeat tract orientation. Furthermore, we demonstrate that transcription and recombination do not influence instability in this system. PMID- 17339224 TI - Neutral evolution of multiple quantitative characters: a genealogical approach. AB - The G matrix measures the components of phenotypic variation that are genetically heritable. The structure of G, that is, its principal components and their associated variances, determines, in part, the direction and speed of multivariate trait evolution. In this article we present a framework and results that give the structure of G under the assumption of neutrality. We suggest that a neutral expectation of the structure of G is important because it gives a null expectation for the structure of G from which the unique consequences of selection can be determined. We demonstrate how the processes of mutation, recombination, and drift shape the structure of G. Furthermore, we demonstrate how shared common ancestry between segregating alleles shapes the structure of G. Our results show that shared common ancestry, which manifests itself in the form of a gene genealogy, causes the structure of G to be nonuniform in that the variances associated with the principal components of G decline at an approximately exponential rate. Furthermore we show that the extent of the nonuniformity in the structure of G is enhanced with declines in mutation rates, recombination rates, and numbers of loci and is dependent on the pattern and modality of mutation. PMID- 17339225 TI - The FLOWERING LOCUS T-like gene family in barley (Hordeum vulgare). AB - The FLOWERING LOCUS T (FT) gene plays a central role in integrating flowering signals in Arabidopsis because its expression is regulated antagonistically by the photoperiod and vernalization pathways. FT belongs to a family of six genes characterized by a phosphatidylethanolamine-binding protein (PEBP) domain. In rice (Oryza sativa), 19 PEBP genes were previously described, 13 of which are FT like genes. Five FT-like genes were found in barley (Hordeum vulgare). HvFT1, HvFT2, HvFT3, and HvFT4 were highly homologous to OsFTL2 (the Hd3a QTL), OsFTL1, OsFTL10, and OsFTL12, respectively, and this relationship was supported by comparative mapping. No rice equivalent was found for HvFT5. HvFT1 was highly expressed under long-day (inductive) conditions at the time of the morphological switch of the shoot apex from vegetative to reproductive growth. HvFT2 and HvFT4 were expressed later in development. HvFT1 was therefore identified as the main barley FT-like gene involved in the switch to flowering. Mapping of HvFT genes suggests that they provide important sources of flowering-time variation in barley. HvFTI was a candidate for VRN-H3, a dominant mutation giving precocious flowering, while HvFT3 was a candidate for Ppd-H2, a major QTL affecting flowering time in short days. PMID- 17339226 TI - Neurospora spore killers Sk-2 and Sk-3 suppress meiotic silencing by unpaired DNA. AB - In Neurospora crassa, pairing of homologous DNA segments is monitored during meiotic prophase I. Any genes not paired with a homolog, as well as any paired homologs of that gene, are silenced during the sexual phase by a mechanism known as meiotic silencing by unpaired DNA (MSUD). Two genes required for MSUD have been described previously: sad-1 (suppressor of ascus dominance), encoding an RNA directed RNA polymerase, and sad-2, encoding a protein that controls the perinuclear localization of SAD-1. Inactivation of either sad-1 or sad-2 suppresses MSUD. We have now shown that MSUD is also suppressed by either of two Spore killer strains, Sk-2 and Sk-3. These were both known to contain a haplotype segment that behaves as a meiotic drive element in heterozygous crosses of killer x sensitive. Progeny ascospores not carrying the killer element fail to mature and are inviable. Crosses homozygous for either of the killer haplotypes suppress MSUD even though ascospores are not killed. The killer activity maps to the same 30-unit-long region within which recombination is suppressed in killer x sensitive crosses. We suggest that the region contains a suppressor of MSUD. PMID- 17339229 TI - Effects of triethylene tetraamine on the G-quadruplex structure in the human c myc promoter. AB - The increasing data show that a parallel G-quadruplex structure formed by the element of nuclease-hypersensitivity element III(1) (NHE III(1)) in the P1 promoter of c-myc functions as a transcriptional repressor. Triethylene tetraamine has exhibited interesting properties of stabilizing both inter- and intra-molecular G-quadruplex structures and telomerase-inhibitory potency. Here, we present evidences showing that triethylene tetraamine facilitates the formation of G-quadruplex structure by the NHE III(1) element, and inhibits the expression of c-myc in HeLa cells. PMID- 17339228 TI - Depolarization-induced rapid generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in rat brain synaptosomes. AB - 2-arachidonoylglycerol (2-AG) is an endogenous ligand for the cannabinoid receptors with a variety of potent biological activities. In this study, we first examined the effects of potassium-induced depolarization on the level of 2-AG in rat brain synaptosomes. We found that a significant amount of 2-AG was generated in the synaptosomes following depolarization. Notably, depolarization did not affect the levels of other molecular species of monoacylglycerols. Furthermore, the level of anandamide was very low and did not change markedly following depolarization. It thus appeared that the depolarization-induced accelerated generation is a unique feature of 2-AG. We obtained evidence that phospholipase C is involved in the generation of 2-AG in depolarized synaptosomes: U73122, a phospholipase C inhibitor, markedly reduced the depolarization-induced generation of 2-AG, and the level of diacylglycerol was rapidly elevated following depolarization. A significant amount of 2-AG was released from synaptosomes upon depolarization. Interestingly, treatment of the synaptosomes with SR141716A, a CB1 receptor antagonist, augmented the release of glutamate from depolarized synaptosomes. These results strongly suggest that the endogenous ligand for the cannabinoid receptors, i.e. 2-AG, generated through increased phospholipid metabolism upon depolarization, plays an important role in attenuating glutamate release from the synaptic terminals by acting on the CB1 receptor. PMID- 17339230 TI - c-Abl tyrosine kinase activates p21 transcription via interaction with p53. AB - c-Abl non-receptor tyrosine kinase has been implicated in many cellular processes including cell differentiation, stress response and regulating gene transcription. The mechanism by which c-Abl is involved in the regulation of gene transcription remains to be elucidated. In this study, we investigated the functions of c-Abl in the activation of p21 promoter. Our results showed that overexpression of c-Abl tyrosine kinase activated p21 promoter and endogenous p21 transcription in U2OS cells. We found that p53 is involved in the activation of p21 promoter by c-Abl, and integrative structure of p53 is required for regulating p21 transcription. In addition, the chromatin immunoprecipitation study demonstrated that c-Abl and p53 can be recruited to the region containing p53 binding site of p21 promoter, and c-Abl increases the DNA binding activity of p53 to the p21 promoter. Furthermore, not only the activation of p21 promoter but also the recruitment to p21 promoter by c-Abl is dependent on the interaction between c-Abl and p53 protein. PMID- 17339231 TI - Beyond the 3' end: experimental validation of extended transcript isoforms. AB - High throughput EST and full-length cDNA sequencing have revealed extensive variations at the 3' ends of mammalian transcripts. Whether all of these changes are biologically meaningful has been the subject of controversy, as such, results may reflect in part transcription or polyadenylation leakage. We selected here a set of tandem poly(A) sites predicted from EST/cDNA sequence analysis that (i) are conserved between human and mouse, (ii) produce alternative 3' isoforms with unusual size features and (iii) are not documented in current genome databases, and we submitted these sites to experimental validation in mouse tissues. Out of 86 tested poly(A) sites from 44 genes, 84 were individually confirmed using a specially devised RT-PCR strategy. We then focused on validating the exon structure between distant tandem poly(A) sites separated by over 3 kb, and between stop codons and alternative poly(A) sites located at 4.5 kb or more, using a long-distance RT-PCR strategy. In most cases, long transcripts spanning the whole poly(A)-poly(A) or stop-poly(A) distance were detected, confirming that tandem sites were part of the same transcription unit. Given the apparent conservation of these long alternative 3' ends, different regulatory functions can be foreseen, depending on the location where transcription starts. PMID- 17339232 TI - Up-regulation of mitochondrial alternative oxidase concomitant with chloroplast over-reduction by excess light. AB - Alternative oxidase (AOX), the unique terminal oxidase in plant mitochondria, catalyzes the energy-wasteful cyanide (CN)-resistant respiration. Although it has been suggested that AOX might prevent chloroplast over-reduction through the efficient dissipation of excess reducing equivalents, direct evidence for this in the physiological context has been lacking. In this study, we examined the mitochondrial respiratory properties, especially AOX, connected to the accumulation of reducing equivalents in the chloroplasts and the activities of enzymes needed to transport the reducing equivalents. We used Arabidopsis thaliana mutants defective in cyclic electron flow around PSI, in which the reducing equivalents accumulate in the chloroplast stroma due to an unbalanced ATP/NADPH production ratio. These mutants showed higher activities of the enzymes needed to transport the reducing equivalents even in low-light growth conditions. The amounts of AOX protein and CN-resistant respiration in the mutants were also higher than those in the wild type. After high-light treatment, AOX, even in the wild type, was preferentially up-regulated concomitant with the accumulation of reducing equivalents in the chloroplasts and an increase in the activities of enzymes needed to transport reducing equivalents. These results indicate that AOX can dissipate the excess reducing equivalents, which are transported from the chloroplasts, and serve in efficient photosynthesis. PMID- 17339233 TI - Fourteenth International Symposium on Microdosimetry. PMID- 17339234 TI - The effects of the selective progesterone receptor modulator asoprisnil on the morphology of uterine tissues after 3 months treatment in patients with symptomatic uterine leiomyomata. AB - BACKGROUND: Asoprisnil is a selective progesterone receptor modulator with mixed progesterone agonist/antagonist activity which controls uterine bleeding via an endometrial effect. This study examined full-thickness endometrial, leiomyoma and myometrial morphology in hysterectomy specimens from patients with uterine leiomyomata, after treatment with asoprisnil for 3 months. METHODS: In this double-blind, randomized, placebo-controlled study, 33 subjects with uterine leiomyomata were randomized to receive asoprisnil 10, 25 mg or placebo for an average of 95 days prior to hysterectomy. Samples of endometrium, myometrium and leiomyoma tissue were subjected to systematic morphological assessment with quantification of mitotic activity. RESULTS: In patients treated with 10 or 25 mg asoprisnil, a unique pattern called 'non-physiologic secretory effect' was evident in endometrium, recognizable through partially developed secretory glandular appearances and stromal changes. Endometrial thickness was decreased, and there were low levels of mitotic activity in endometrial glands and stroma. Unusual thick-walled muscular arterioles and prominent aggregations of thin walled vessels were present in endometrial stroma, but not in myometrium or non endometrial vascular beds. Mitotic activity was decreased in leiomyomata. CONCLUSIONS: Asoprisnil induces unique morphological changes and is associated with low levels of glandular and stromal proliferation in endometrium, and in leiomyomata. These changes are likely to contribute to the amenorrhoea experienced after exposure to the medication. PMID- 17339227 TI - Comparative physical mapping between Oryza sativa (AA genome type) and O. punctata (BB genome type). AB - A comparative physical map of the AA genome (Oryza sativa) and the BB genome (O. punctata) was constructed by aligning a physical map of O. punctata, deduced from 63,942 BAC end sequences (BESs) and 34,224 fingerprints, onto the O. sativa genome sequence. The level of conservation of each chromosome between the two species was determined by calculating a ratio of BES alignments. The alignment result suggests more divergence of intergenic and repeat regions in comparison to gene-rich regions. Further, this characteristic enabled localization of heterochromatic and euchromatic regions for each chromosome of both species. The alignment identified 16 locations containing expansions, contractions, inversions, and transpositions. By aligning 40% of the punctata BES on the map, 87% of the punctata FPC map covered 98% of the O. sativa genome sequence. The genome size of O. punctata was estimated to be 8% larger than that of O. sativa with individual chromosome differences of 1.5-16.5%. The sum of expansions and contractions observed in regions >500 kb were similar, suggesting that most of the contractions/expansions contributing to the genome size difference between the two species are small, thus preserving the macro-collinearity between these species, which diverged approximately 2 million years ago. PMID- 17339235 TI - The expression of polymerase gamma and mitochondrial transcription factor A and the regulation of mitochondrial DNA content in mature human sperm. AB - BACKGROUND: Human mitochondrial DNA (mtDNA) encodes 13 polypeptides of the electron transfer chain. Its replication is dependent on the nuclear-encoded polymerase gamma (POLG) and mitochondrial transcription factor A (TFAM). For POLG, only the polyglutamine tract, characterized by a series of CAG repeats, has been investigated in human sperm. However, TFAM is associated with the reduction in mtDNA content of testicular sperm. We have determined whether POLG and TFAM have functional roles in post-ejaculatory sperm mtDNA. METHODS: Sperm samples were categorized as: normals, samples with one or two abnormal sperm parameters and oligoasthenoteratozoospermics (OATs). These were analysed by fluorescent PCR to determine the number of CAG repeats, real-time PCR for mtDNA copy number and immunocytochemistry and western blotting for patterns of expression for POLG, TFAM and the mtDNA-encoded COXI. RESULTS: Only the OAT group presented with a significantly higher incidence of heterozygosity for CAG repeats, higher mtDNA content and a lower percentage of sperm expressing POLG and TFAM. Paradoxically, good-quality sperm had fewer mtDNA copies but significantly more sperm expressed POLG, TFAM and COXI. CONCLUSIONS: Our data support the original findings that an association between sperm quality and POLG CAG repeats does exist. However, the biological significance of these variants in male infertility remains unclear, as these do not seem to affect mtDNA maintenance. The reduction in mtDNA content in normal samples likely reflects normal spermiogenesis, whereas increases in POLG and TFAM expression possibly compensate for the low mtDNA content, maintaining mitochondrial homeostasis. PMID- 17339236 TI - Cost effectiveness of clinically appropriate decisions on alternative treatments for angina pectoris: prospective observational study. AB - OBJECTIVE: To assess whether revascularisation that is considered to be clinically appropriate is also cost effective. DESIGN: Prospective observational study comparing cost effectiveness of coronary artery bypass grafting, percutaneous coronary intervention, or medical management within groups of patients rated as appropriate for revascularisation. SETTING: Three tertiary care centres in London. PARTICIPANTS: Consecutive, unselected patients rated as clinically appropriate (using a nine member Delphi panel) to receive coronary artery bypass grafting only (n=815); percutaneous coronary intervention only (n=385); or both revascularisation procedures (n=520). MAIN OUTCOME MEASURE: Cost per quality adjusted life year gained over six year follow-up, calculated with a National Health Service cost perspective and discounted at 3.5%/year. RESULTS: Coronary artery bypass grafting cost 22,000 pounds sterling (33,000 euros; $43,000) per quality adjusted life year gained compared with percutaneous coronary intervention among patients appropriate for coronary artery bypass grafting only (59% probability of being cost effective at a cost effectiveness threshold of 30,000 pounds sterling per quality adjusted life year) and 19,000 pounds sterling per quality adjusted life year gained compared with medical management among those appropriate for both types of revascularisation (probability of being cost effective 63%). In none of the three appropriateness groups was percutaneous coronary intervention cost effective at a threshold of 30,000 pounds sterling per quality adjusted life year. Among patients rated appropriate for percutaneous coronary intervention only, the cost per quality adjusted life year gained for percutaneous coronary intervention compared with medical management was 47,000, pounds sterling exceeding usual cost effectiveness thresholds; in these patients, medical management was most likely to be cost effective (probability 54%). CONCLUSIONS: Among patients judged clinically appropriate for coronary revascularisation, coronary artery bypass grafting seemed cost effective but percutaneous coronary intervention did not. Cost effectiveness analysis based on observational data suggests that the clinical benefit of percutaneous coronary intervention may not be sufficient to justify its cost. PMID- 17339237 TI - Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype-low (CIMP-low) in colorectal cancer. AB - BACKGROUND: The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer. In contrast, a phenotype with less widespread promoter methylation (CIMP low) has not been well characterised. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and silencing have been associated with G>A mutations and microsatellite instability-low (MSI-low). AIM: To examine molecular correlates with MGMT methylation/silencing in colorectal cancer. METHODS: Utilising MethyLight technology, we quantified DNA methylation in MGMT and eight other markers (a CIMP-diagnostic panel; CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) in 920 population-based colorectal cancers. RESULTS: Tumours with both MGMT methylation and loss were correlated positively with MSI-low (p = 0.02), CIMP-high (>or=6/8 methylated CIMP markers, p = 0.005), CIMP-low (1/8-5/8 methylated CIMP markers, p = 0.002, compared to CIMP-0 with 0/8 methylated markers), KRAS G>A mutation (p = 0.02), and inversely with 18q loss of heterozygosity (p = 0.0002). Tumours were classified into nine MSI/CIMP subtypes. Among the CIMP-low group, tumours with both MGMT methylation and loss were far more frequent in MSI-low tumours (67%, 12/18) than MSI-high tumours (5.6%, 1/18; p = 0.0003) and microsatellite stable (MSS) tumours (33%, 52/160; p = 0.008). However, no such relationship was observed among the CIMP-high or CIMP-0 groups. CONCLUSION: The relationship between MGMT methylation/silencing and MSI-low is limited to only CIMP-low tumours, supporting the suggestion that CIMP-low in colorectal cancer may be a different molecular phenotype from CIMP-high and CIMP 0. Our data support a molecular difference between MSI-low and MSS in colorectal cancer, and a possible link between CIMP-low, MSI-low, MGMT methylation/loss and KRAS mutation. PMID- 17339238 TI - Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. AB - BACKGROUND: We previously showed that neonatal maternal separation (MS) of rat pups causes immediate and long-term changes in intestinal physiology. AIM: To examine if administration of probiotics affects MS-induced gut dysfunction. METHODS: MS pups were separated from the dam for 3 h/day from days 4 to 19; non separated (NS) pups served as controls. Twice per day during the separation period, 10(8) probiotic organisms (two strains of Lactobacillus species) were administered to MS and NS pups; vehicle-treated pups received saline. Studies were conducted on day 20, when blood was collected for corticosterone measurement as an indication of hypothalamus-pituitary-adrenal (HPA) axis activity, and colonic function was studied in tissues mounted in Ussing chambers. Ion transport was indicated by baseline and stimulated short-circuit current (Isc); macromolecular permeability was measured by flux of horseradish peroxidase (HRP) across colonic tissues; and bacterial adherence/penetration into the mucosa was quantified by culturing tissues in selective media. Colonic function and host defence were also evaluated at day 60. RESULTS: Isc and HRP flux were significantly higher in the colon of MS versus NS pups. There was increased adhesion/penetration of total bacteria in MS pups, but a significant reduction in Lactobacillus species. Probiotic administration ameliorated the MS-induced gut functional abnormalities and bacterial adhesion/penetration at both day 20 and 60, and reduced the elevated corticosterone levels at day 20. CONCLUSIONS: The results indicate that altered enteric flora are responsible for colonic pathophysiology. Probiotics improve gut dysfunction induced by MS, at least in part by normalisation of HPA axis activity. PMID- 17339239 TI - Treatment of oesophageal ulcerations using endoscopic transplantation of tissue engineered autologous oral mucosal epithelial cell sheets in a canine model. PMID- 17339240 TI - Therapeutic potential of fractalkine: a novel approach to metastatic colon cancer. PMID- 17339241 TI - Mechanisms of epithelial dysfunction in giardiasis. PMID- 17339242 TI - DNA alkylation and DNA methylation: cooperating mechanisms driving the formation of colorectal adenomas and adenocarcinomas? PMID- 17339243 TI - When does severe diarrhoea disclose a hereditary disease? PMID- 17339245 TI - A life-threatening complication of a life-saving manoeuvre. PMID- 17339247 TI - Malignant masquerade of the biliary confluence. PMID- 17339249 TI - Treatment of patients with lamivudine-resistant and adefovir dipivoxil-resistant chronic hepatitis B virus infection: is tenofovir the answer? PMID- 17339250 TI - Re: long term follow up of patients treated for Helicobacter pylori infection. PMID- 17339251 TI - Further evidence supporting a psychological component to irritable bowel syndrome. PMID- 17339252 TI - Abdominal epilepsy, an uncommon cause of recurrent abdominal pain: a brief report. PMID- 17339253 TI - The pattern of cytokine expression determines the degree of mucosal damage. PMID- 17339254 TI - Weight loss induced by orlistat reverses fatty infiltration and improves hepatic fibrosis in obese patients with non-alcoholic steatohepatitis. PMID- 17339255 TI - Screening for coeliac disease in patients fulfilling the Rome II criteria for irritable bowel syndrome in a secondary care hospital in The Netherlands: a prospective observational study. PMID- 17339256 TI - Functional polymorphisms in the promoters of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12 and MMP-13 are not associated with hepatocellular carcinoma risk. PMID- 17339257 TI - Acute surgical abdomen: an atypical presentation of Plasmodium vivax malaria. PMID- 17339258 TI - Octreotide LAR for severe obscure-overt gastrointestinal haemorrhage in high-risk patients on anticoagulation therapy. PMID- 17339259 TI - Submucosal xanthachromia after endoscopic mucosal resection: laparotomy or conservative therapy? PMID- 17339260 TI - Complete response in a patient with colonic mantle cell lymphoma with multiple lymphomatous polyposis treated with combination chemotherapy using anti-CD20 antibody and cladribine. PMID- 17339261 TI - Response from the hornet's nest: furthering the debate on transplantation for alcoholic liver disease. PMID- 17339262 TI - Patients with functional constipation do not have increased prevalence of colorectal cancer precursors. PMID- 17339263 TI - Bone marrow for cardiac repair: the importance of characterizing the phenotype and function of injected cells. PMID- 17339264 TI - Hypertrophy and inflammation: too much for one heart. PMID- 17339265 TI - Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study. AB - AIM: To describe temporal profiles of plasma matrix metalloproteinases (MMP-2 and MMP-9), and their relationship with echocardiographic (Echo) parameters of left ventricular (LV) function and remodelling, after acute myocardial infarction (AMI) in man. METHODS AND RESULTS: Plasma MMP-2 and MMP-9 were assayed at intervals (0-12, 12-24, 24-48, 48-72, 72-96, and > 96 h) in 91 patients with AMI (ST-elevation/non-ST-elevation 77/24; 73% male; 40% anterior site) and on a single occasion in 172 age- and sex-matched control subjects with stable coronary artery disease. Echo assessment of LV volumes, LV ejection fraction (LVEF), and wall motion index score were assessed before discharge and at follow-up (median 176, range 138-262 days) for patients and on a single occassion in controls. Plasma MMP-2 was similar at all times after AMI, elevated when compared with control (P = 0.005-0.001) and unrelated to LV function or volume during index admission or at follow-up. Maximal MMP-9 was seen at 0-12 h and was elevated when compared with control (P = 0.002) followed by fall to a plateau. Both maximal and plateau MMP-9 concentration correlated with white blood cell (WBC, P = 0.023 to < 0.001) and neutrophil count (P = 0.014 to < 0.001). Maximal MMP-9 had independent predictive value for lower LVEF (P = 0.004) during admission and for greater change in LV end-diastolic volume between admission and follow-up (R = 0.3, P = 0.016). In contrast, higher plateau levels of MMP-9 were associated with relative preservation of LV function (increasing LVEF, P = 0.002; decreasing WMIS, P = 0.009) and less change in end-systolic volume and end-diastolic volumes after discharge (P = 0.001 and 0.024, respectively). CONCLUSION: Both MMP-9 and MMP-2 are elevated following AMI. The biphasic profile of plasma MMP-9 is related to LV remodelling and function following AMI in man. Higher early levels of MMP-9 associate with the extent of LV remodelling and circulating WBC levels. In contrast, higher plateau levels later after AMI are associated with relative preservation of LV function. Temporal profile, rather than absolute magnitude, of MMP-9 activity appears to be important for LV remodelling after AMI. PMID- 17339266 TI - Right ventricular involvement in Takotsubo cardiomyopathy. PMID- 17339267 TI - Assessment and disease comparisons of hybrid developmental defects. AB - Rodents of the genus Peromyscus are among the most common North American mammals. Crosses between natural populations of two of these species, P. maniculatus (BW) and P. polionotus (PO), produce parent-of-origin effects on growth and development. BW females mated to PO males produce growth-retarded offspring. In contrast, PO females mated to BW males produce overgrown but dysmorphic conceptuses. Variation in imprinted loci and control of genomic imprinting appear to underlie the hybrid effects. Prior morphological and genetic analyses have focused on placental and post-natal growth. Here, we assess the frequency and scope of embryonic defects. The most frequent outcome of the PO x BW cross is death prior to embryonic day 13. Conceptuses lacking an embryo proper are also observed as in gestational trophoblast disease. Among the common embryonic phenotypes described and tabulated are edema, blood vessel enlargement/hemorrhaging, macroglossia, retention of nucleated erythrocytes, placentomegaly. We investigate expression of loci known to be mis-regulated in human growth/placental disorders and/or mouse knockouts with similar phenotypes. These loci are Igf2, Cdkn1c, Grb10, Gpc3, Phlda2 and Rb1. All exhibited significant differences in either placental or embryonic expression levels at one or more of the three timepoints examined. The data underscore the importance of placental gene expression on embryonic defects. We suggest that the hybrid defects offer a novel system to understand how natural allelic combinations interact to produce disease phenotypes. We propose that such interactions and their resulting epimutations may similarly underlie the phenotypic and causal heterogeneity seen in many human diseases. PMID- 17339268 TI - Trisomy for the Down syndrome 'critical region' is necessary but not sufficient for brain phenotypes of trisomic mice. AB - Trisomic Ts65Dn mice show direct parallels with many phenotypes of Down syndrome (DS), including effects on the structure of cerebellum and hippocampus. A small segment of Hsa21 known as the 'DS critical region' (DSCR) has been held to contain a gene or genes sufficient to cause impairment in learning and memory tasks involving the hippocampus. To test this hypothesis, we developed Ts1Rhr and Ms1Rhr mouse models that are, respectively, trisomic and monosomic for this region. Here, we show that trisomy for the DSCR alone is not sufficient to produce the structural and functional features of hippocampal impairment that are seen in the Ts65Dn mouse and DS. However, when the critical region is returned to normal dosage in trisomic Ms1Rhr/Ts65Dn mice, performance in the Morris water maze is identical to euploid, demonstrating that this region is necessary for the phenotype. Thus, although the prediction of the critical region hypothesis was disproved, novel gene dosage effects were identified, which help to define how trisomy for this segment of the chromosome contributes to phenotypes of DS. PMID- 17339269 TI - A common haplotype of the annexin A5 (ANXA5) gene promoter is associated with recurrent pregnancy loss. AB - We sought to verify whether variation in the promoter of the gene encoding placental anticoagulant protein annexin A5 (ANXA5) represents a risk factor for recurrent pregnancy loss (RPL). Sequence analysis of 70 German RPL patients, all known to carry neither factor V Leiden nor a prothrombin mutation, revealed four consecutive nucleotide substitutions in the ANXA5 promoter, which were transmitted as a joint haplotype (M2). Reporter gene assays revealed that M2 reduces the in vitro activity of the ANXA5 promoter to 37-42% of the normal level. The possible relationship between M2 and RPL was evaluated by comparing RPL patients with two independent control groups recruited from the registry of the Institut fur Humangenetik in Munster and the PopGen biobank in Kiel, respectively. Carriers of M2 were found to exhibit a > 2-fold higher RPL risk than non-carriers (odds ratio, 2.42; 95% confidence interval, 1.27-4.58) when using unselected controls (PopGen) and an almost 4-fold higher risk when using the Munster 'super-controls', i.e. women with successful pregnancies and no previous history of pregnancy losses (odds ratio, 3.88; 95% confidence interval, 1.98-7.54). This statistically significant association should facilitate the development of improved prognostic algorithms for RPL, involving a more precise assessment of individual disease risks, and provide a guide to offering adequate therapies where relevant. PMID- 17339271 TI - Heritable rather than age-related environmental and stochastic factors dominate variation in DNA methylation of the human IGF2/H19 locus. AB - Epigenetic variation may significantly contribute to the risk of common disease. Currently, little is known about the extent and causes of epigenetic variation. Here, we investigated the contribution of heritable influences and the combined effect of environmental and stochastic factors to variation in DNA methylation of the IGF2/H19 locus. Moreover, we tested whether this locus was subject to age related degeneration of epigenetic patterns as was previously suggested for global methylation. We measured methylation of the H19 and IGF2 differentially methylated regions (DMRs) in 196 adolescent and 176 middle-aged twins using a recently developed mass spectrometry-based method. We observed substantial variation in DNA methylation across individuals, underscoring that DNA methylation is a quantitative trait. Analysis of data in monozygotic and dizygotic twins revealed that a significant part of this variation could be attributed to heritable factors. The heritability of methylation of individual CpG sites varied between 20 and 74% for the H19 DMR and was even higher, between 57 and 97%, for the IGF2 DMR. Remarkably, the combined influence of environmental and stochastic factors on DNA methylation was not greater in middle-age than in adolescence, suggesting a limited role for age-related degeneration of methylation patterns at this locus. Single nucleotide polymorphisms in the IGF2/H19 locus were significantly associated with DNA methylation of the IGF2 DMR (P = 0.004). A preliminary analysis suggested an association between H19 DMR methylation and body size (P < 0.05). Our study shows that variation in DNA methylation of the IGF2/H19 locus is mainly determined by heritable factors and single nucleotide polymorphisms (SNPs) in cis, rather than the cumulative effect of environmental and stochastic factors occurring with age. PMID- 17339270 TI - 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. AB - Human chromosome 15q11-13 is a complex locus containing imprinted genes as well as a cluster of three GABA(A) receptor subunit (GABR) genes-GABRB3, GABRA5 and GABRG3. Deletion or duplication of 15q11-13 GABR genes occurs in multiple human neurodevelopmental disorders including Prader-Willi syndrome (PWS), Angelman syndrome (AS) and autism. GABRB3 protein expression is also reduced in Rett syndrome (RTT), caused by mutations in MECP2 on Xq28. Although Gabrb3 is biallelically expressed in mouse brain, conflicting data exist regarding the imprinting status of the 15q11-13 GABR genes in humans. Using coding single nucleotide polymorphisms we show that all three GABR genes are biallelically expressed in 21 control brain samples, demonstrating that these genes are not imprinted in normal human cortex. Interestingly, four of eight autism and one of five RTT brain samples showed monoallelic or highly skewed allelic expression of one or more GABR gene, suggesting that epigenetic dysregulation of these genes is common to both disorders. Quantitative real-time RT-PCR analysis of PWS and AS samples with paternal and maternal 15q11-13 deletions revealed a paternal expression bias of GABRB3, while RTT brain samples showed a significant reduction in GABRB3 and UBE3A. Chromatin immunoprecipitation and bisulfite sequencing in SH SY5Y neuroblastoma cells demonstrated that MeCP2 binds to methylated CpG sites within GABRB3. Our previous studies demonstrated that homologous 15q11-13 pairing in neurons was dependent on MeCP2 and was disrupted in RTT and autism cortex. Combined, these results suggest that MeCP2 acts as a chromatin organizer for optimal expression of both alleles of GABRB3 in neurons. PMID- 17339272 TI - PD-L1 partially protects renal tubular epithelial cells from the attack of CD8+ cytotoxic T cells. AB - BACKGROUND: Activated infiltrating T cells play a crucial role in nephritic inflammation via the direct interaction with proximal tubular epithelial cells (TEC). Under inflammatory conditions, major histocompatibility complex class I and II molecules are upregulated on the surface of renal TEC, enabling them to function as "non-professional" antigen-presenting cells (APC) to activate T cells, and, in turn to be targeted by cytotoxic T lymphocytes (CTL) to cause tissue damage. It is known that co-stimulatory (e.g. B7/CD28) and co-inhibitory (e.g. PD-L1/PD-1) signals regulate and determine the magnitude of T cell responses. In this study, we examined the expression of co-stimulatory molecule PD-L1 by renal TEC and the functional role of renal PD-L1/PD-1 pathway in regulating CD8+ T cell responses induced by antigen-presenting renal TEC. METHODS: Renal TEC were treated with type I and type II interferons (IFN-alpha, IFN-beta or IFN-gamma). PD-L1 expression was then determined with flow cytometry and RT-PCR. To investigate the functional role of renal epithelial PD-L1 on CD8+ CTL responses, H-2K(b)-restricted, OVA(257-264) peptide-specific CD8+ T cells isolated from OT-1 T cell receptor transgenic mice were co-incubated with IFN stimulated, OVA(257-264) peptide-pulsed congeneic TEC. The activation of OT-1 CD8+ CTL was estimated either by IFN-gamma production in the supernatants of co cultures or by CTL activity. RESULTS: TECs do not constitutively express PD-L1 on their surface. However, a strong and dose-dependent upregulation of PD-L1 was observed on TEC after stimulation with IFN-beta or IFN-gamma, but not with IFN alpha. OVA(257-264) peptide pulsed-TEC were able to activate OT-1 CD8+ T cells, indicated by the high amount of IFN-gamma production and cytolysis of TEC. Blockade of epithelial PD-L1 with specific mAb significantly increased OT-1 CD8+ T cell activity, indicating that the PD-L1 pathway has a negative effect on CD8+ T cell responses. Moreover, IFN- beta- or IFN-gamma-stimulated TEC with high surface PD-L1 expression were more resistant to the cytolysis by OT-1 CTL. CONCLUSION: Together our data reveal that the renal PD-L1/PD-1 pathway has a negative effect on CD8+ CTL activation. PD-L1 might, therefore, act as a protective molecule on TEC, downregulating the cytotoxic renal parenchymal immune response. PMID- 17339273 TI - Cardiovascular disease prevention in primary care. AB - Since the publication of the National Service Framework for coronary heart disease, there has been a move towards primary disease prevention with a greater focus on an individual's absolute risk. Meta-analysis and systematic reviews of the evidence for primary prevention are incomplete and the current guidelines and policy have led to considerable confusion in clinical practice. There is an increased use of risk assessment tools but no effective method of reviewing current activity with the limited integration into the existing Quality Outcome Framework. There is an inadequate evidence for some of the risk factors used to identify individuals at risk, the risk calculators used to quantify the degree of risk and the methods of communicating risk to patients are largely unproven or completely missing. There is a need for a co-ordinated vascular disease prevention programme which can be applied at the individual and at the population level but is also amenable to evaluation. PMID- 17339275 TI - Genetics of phaeochromocytoma. AB - Recent advances in determining the molecular basis for phaeochromocytoma susceptibility have revealed a much larger inherited contribution to the pathogenesis of phaeochromocytoma than had been generally recognized. The identification of individuals with phaeochromocytoma susceptibility disorders (e.g. von Hippel-Lindau disease, succinate dehydrogenase subunit mutations, multiple endocrine neoplasia type 2 and neurofibromatosis type 1) is important because of the opportunity to reduce morbidity and mortality from phaeochromocytoma and other relevant tumours in affected individuals and their at risk relatives. Recent studies have also provided clues to the molecular pathogenesis of phaeochromocytoma development in familial cases and suggest that this differs from that seen in sporadic non-inherited cases. PMID- 17339276 TI - Mycorrhizal acquisition of inorganic phosphorus by the green-leaved terrestrial orchid Goodyera repens. AB - BACKGROUND AND AIMS: Mycorrhizal fungi play a vital role in providing a carbon subsidy to support the germination and establishment of orchids from tiny seeds, but their roles in adult orchids have not been adequately characterized. Recent evidence that carbon is supplied by Goodyera repens to its fungal partner in return for nitrogen has established the mutualistic nature of the symbiosis in this orchid. In this paper the role of the fungus in the capture and transfer of inorganic phosphorus (P) to the orchid is unequivocally demonstrated for the first time. METHODS: Mycorrhiza-mediated uptake of phosphorus in G. repens was investigated using spatially separated, two-dimensional agar-based microcosms. RESULTS: External mycelium growing from this green orchid is shown to be effective in assimilating and transporting the radiotracer (33)P orthophosphate into the plant. After 7 d of exposure, over 10 % of the P supplied was transported over a diffusion barrier by the fungus and to the plants, more than half of this to the shoots. CONCLUSIONS: Goodyera repens can obtain significant amounts of P from its mycorrhizal partner. These results provide further support for the view that mycorrhizal associations in some adult green orchids are mutualistic. PMID- 17339277 TI - Differences in phenotypic and genotypic traits against antimicrobial agents between Acinetobacter baumannii and Acinetobacter genomic species 13TU. AB - OBJECTIVES: To investigate the differences in antimicrobial susceptibility and resistance mechanisms against imipenem between Acinetobacter baumannii and Acinetobacter genomic species 13TU. METHODS: A total of 232 non-duplicate Acinetobacter species were consecutively collected from two Korean hospitals in Daegu, Republic of Korea, between November 2004 and November 2005. Antimicrobial susceptibility was determined by agar dilution methods. Resistance to imipenem was characterized by a carbapenemase activity test and PCR amplification. PFGE was performed to determine the clonal relatedness of imipenem-resistant Acinetobacter species. RESULTS: A. baumannii was the most prevalent species (61.2%), followed by Acinetobacter genomic species 13TU (25.9%). The resistance rates of A. baumannii to most antimicrobial agents were higher than those of other Acinetobacter species, while the resistance rate to imipenem was the highest in Acinetobacter genomic species 13TU. Imipenem-resistant Acinetobacter genomic species 13TU isolates produced VIM-2 metallo-beta-lactamase, while imipenem-resistant A. baumannii isolates produced OXA-23 and/or OXA-51 beta lactamase. Imipenem-resistant Acinetobacter strains originated from different clones in each hospital. CONCLUSIONS: Two prevalent Acinetobacter species, A. baumannii and Acinetobacter genomic species 13TU, possess distinct phenotypic and genotypic traits against antimicrobials. PMID- 17339278 TI - Gene expression profiling of the response of Streptococcus pneumoniae to penicillin. AB - OBJECTIVES: The aim of this study was to identify changes in the gene expression profile of Streptococcus pneumoniae in response to a subinhibitory concentration of penicillin in an effort to better understand mechanisms by which this organism copes with this stress. METHODS: S. pneumoniae serotype 2 strain D39 was grown for 1 h in the presence or absence of penicillin at a concentration equivalent to half the MIC (0.03 mg/L). RNA was isolated and gene expression profiles were compared using DNA microarrays. Differential expression of select genes was confirmed by real-time RT-PCR. RESULTS: A total of 386 genes were found to be responsive to penicillin. Up-regulated genes included those of the ciaR-ciaH operon, luxS, genes encoding cell envelope proteins and genes of the pst locus. Down-regulated genes included genes involved in competence, genes encoding capsular polysaccharide biosynthesis proteins, genes involved in fatty acid chain elongation and genes of the polyamine transporter operon. CONCLUSIONS: Altered expression of these genes reflects a protective response to perturbation of the bacterial cell wall by penicillin. Such genes may represent potential therapeutic targets for enhancing the activity of penicillin against this organism and provide insight into novel mechanisms of penicillin resistance. PMID- 17339279 TI - Flucytosine therapeutic monitoring: 15 years experience from the UK. AB - BACKGROUND: There is uniform consensus that flucytosine blood concentrations should be measured to avoid toxicity and ensure adequate efficacy. OBJECTIVES AND METHODS: The purpose of this study was to evaluate all flucytosine levels performed in a regional centre in the UK from October 1991 to May 2006. Concentrations were measured by bioassay. RESULTS: We reviewed 1071 flucytosine levels in 233 patients, including 33 neonates. Overall, only 20.5% of levels were in the expected therapeutic range. Low levels were observed in 40.5%, of which 5.1% were undetectable levels (<12.5 mg/L). High levels occurred in 38.9%, of which 9.9% were considered potentially toxic (>100 mg/L). High flucytosine levels occurred more frequently amongst neonates, which could be related to an immature renal system resulting in drug accumulation. CONCLUSIONS: Our findings reveal that the vast majority of patients were out of range for flucytosine levels. These data emphasize the importance of monitoring flucytosine levels. PMID- 17339280 TI - Comparison of cefoxitin and moxalactam 30 microg disc diffusion methods for detection of methicillin resistance in coagulase-negative staphylococci. AB - OBJECTIVES: To compare cefoxitin and/or moxalactam 30 microg disc diffusion (DD) methods to detect methicillin resistance in coagulase-negative staphylococci (CoNS) using both high- and low-density (HD/LD) inoculum techniques. METHODS: A challenge set of 192 CoNS was tested. DD test results were compared with PBP2a detection. RESULTS: With the LD inoculum, the sensitivity/specificity of cefoxitin and moxalactam were 94.4%/100% and 100%/92.4%, respectively, using the DD breakpoints of the Comite de l'Antibiogramme de la Societe Francaise de Microbiologie. With the HD inoculum, the sensitivity/specificity of cefoxitin and moxalactam were 93.7%/100% and 100%/96.9%, using the cefoxitin DD breakpoints of the CLSI and a resistant/susceptible breakpoint of < 20 mm/>or=20 mm for moxalactam. Comparison of receiver operating characteristic AUCs did not show significant difference between studied assays, but the overlapping zone where both PBP2a-positive and PBP2a-negative isolates were observed concerned a lower number of strains with moxalactam than with cefoxitin (P < 0.001). Combination of cefoxitin and moxalactam DD methods demonstrated that all isolates with a concordant cefoxitin/moxalactam phenotype were correctly classified. Interestingly, all isolates misclassified by each DD method used alone were cefoxitin-susceptible and moxalactam-resistant. CONCLUSIONS: Although all DD methods studied here performed well for detecting methicillin resistance in CoNS, moxalactam had a higher accuracy than cefoxitin to differentiate heteroresistant isolates from PBP2a-negative strains. Identification of isolates that should be submitted to a confirmatory test to conclude on methicillin resistance can be easily obtained by combining cefoxitin and moxalactam DD methods. PMID- 17339281 TI - Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface. AB - Galectin-8 has two different carbohydrate recognition domains (CRDs), the N terminal Gal-8N and the C-terminal Gal-8C linked by a peptide, and has various effects on cell adhesion and signaling. To understand the mechanism for these effects further, we compared the binding activities of galectin-8 in solution with its binding and activation of cells. We used glycan array analysis to broaden the specificity profile of the two galectin-8 CRDs, as well as intact galectin-8s (short and long linker), confirming the unique preference for sulfated and sialylated glycans of Gal-8N. Using a fluorescence anisotropy assay, we examined the solution affinities for a subset of these glycans, the highest being 50 nM for NeuAcalpha2,3Lac by Gal-8N. Thus, carbohydrate-protein interactions can be of high affinity without requiring multivalency. More importantly, using fluorescence polarization, we also gained information on how the affinity is built by multiple weak interactions between different fragments of the glycan and its carrier molecule and the galectin CRD subsites (A-E). In intact galectin-8 proteins, the two domains act independently of each other in solution, whereas at a surface they act together. Ligands with moderate or weak affinity for the isolated CRDs on the array are bound strongly by intact galectin 8s. Also galectin-8 binding and signaling at cell surfaces can be explained by combined binding of the two CRDs to low or medium affinity ligands, and their highest affinity ligands, such as sialylated galactosides, are not required. PMID- 17339282 TI - Second metatarsal stress fracture in sport: comparative risk factors between proximal and non-proximal locations. AB - BACKGROUND: Stress fractures of the second metatarsal are common injuries in athletes and military recruits. There are two distinct areas in the second metatarsal where stress fractures develop: one proximal (at the base) and the other non-proximal (distal). Diagnosis can be difficult, and there is a difference in prognosis and treatment of the two types of stress fracture. Therefore differentiation of fracture location is warranted. Differences in risk factors and clinical outcomes between proximal and non-proximal stress fractures have not been studied. OBJECTIVE: To determine whether different risk factors and/or clinical outcomes associated with proximal and non-proximal stress fractures of the second metatarsal exist. METHODS: Patients diagnosed with proximal stress fractures of the second metatarsal were included in the study. Retrospectively, an age-matched control group with a non-proximal stress fracture was selected for comparison. Statistical analysis involved bivariate comparisons of demographic variables and clinical measurement between the two groups. RESULTS: Patients with proximal stress fractures were more likely to be chronically affected, usually exhibited an Achilles contracture, showed differences in length of first compared with second metatarsal, were more likely to experience multiple stress fractures, and exhibited low bone mass. In addition, a high degree of training slightly increased the risk of a non-proximal fracture, whereas low training volume was associated with a proximal stress fracture. CONCLUSION: The signs, symptoms and clinical findings associated with proximal metatarsal stress fractures are different from those of non-proximal stress fractures. PMID- 17339283 TI - Retrospective evaluation of three treatment methods for primary hyperparathyroidism in dogs. AB - The medical records of 110 dogs treated for primary hyperparathyroidism were reviewed. Dogs were treated via parathyroidectomy (n=47), percutaneous ultrasound guided ethanol ablation (n=15), or percutaneous ultrasound-guided heat ablation (n=48). Forty-five of 48 (94%) parathyroidectomies resulted in control of hypercalcemia for a median of 561 days. Thirteen of 18 (72%) ethanol ablation procedures resulted in control of hypercalcemia for a median of 540 days. Forty four of 49 (90%) heat-ablation treatments resulted in control of hypercalcemia for a median of 581 days. PMID- 17339284 TI - Ultrasonographic visualization of the adrenal glands of healthy ferrets and ferrets with hyperadrenocorticism. AB - A protocol was developed to compare the ultrasonographic characteristics of the adrenal glands of 21 healthy ferrets and 37 ferrets with hyperadrenocorticism. By using specific landmarks, the adrenal glands were imaged in 97% of the cases. The adrenal glands of ferrets with hyperadrenocorticism had a significantly increased thickness, with changes in shape, structure, and echogenicity compared to the adrenal glands of healthy ferrets. Based on the findings of the study, adrenal glands may be classified as abnormal when they have a rounded appearance, increased size of the cranial/caudal pole (thickness >3.9 mm), a heterogeneous structure, increased echogenicity, and/or signs of mineralization. PMID- 17339285 TI - Reevaluation of the University of Wisconsin 2-year protocol for treating canine lymphosarcoma. AB - This retrospective study investigated a population of 96 dogs with newly diagnosed malignant lymphosarcoma that were treated with the commonly used University of Wisconsin-Madison (UW-M) chemotherapy protocol. Pretreatment characteristics were analyzed to determine prognostic factors. Dogs with higher World Health Organization (WHO) stages (including stage IV) and dogs with hypercalcemia were at significantly higher risk of relapse (P=0.018 and P=0.016, respectively). Dose reduction, treatment delays, and prior therapy with cortico steroids were not associated with clinical outcome. First remission duration of 270 days was similar to historically reported data. Overall survival time of 218 days was much shorter than historical data. PMID- 17339286 TI - Tibial plateau symmetry and the effect of osteophytosis on tibial plateau angle measurements. AB - A novel technique was developed to estimate the caudal medial tibial plateau landmark in the face of osteophytosis to improve accuracy in tibial plateau angle measurements. Using this technique, tibial plateau angles were evaluated in 31 normal dogs before and 8 months after right cranial cruciate ligament transection. There was no significant difference in mean tibial plateau angle before or after induction of osteophytosis. Additionally, it was determined that 90% of dogs had a difference of =2 degrees between right and left tibial plateau angles, which was considered symmetrical. PMID- 17339287 TI - Computed tomographic diagnosis of nongastrointestinal foreign bodies in dogs. AB - Clinical data and computed tomography (CT) studies were reviewed for 13 dogs with confirmed nongastrointestinal foreign bodies. Locations of foreign bodies were the nasal cavity, thoracic wall, retropharyngeal region, and cerebellum. Types of foreign bodies included small plant components, blades of grass, wooden sticks, cloth fibers, and a needle. Foreign bodies in five dogs were not identified on CT, and secondary reactions resembled neoplastic or fungal disease. In eight dogs, foreign bodies were recognized by their shape and/or internal architecture. In two dogs, three-dimensional reformatting helped demonstrate foreign bodies in relation to palpable bony landmarks. PMID- 17339288 TI - Ultrasound-assisted drainage and alcoholization of hepatic and renal cysts: 22 cases. AB - Twenty-two dogs and cats with symptomatic renal or hepatic cysts that had undergone ultrasound-assisted drainage and alcoholization were retrospectively evaluated. Common presenting complaints were anorexia, reluctance to move, and vomiting. Abdominal pain was observed in all cases. Systemic hypertension was identified in four dogs and four cats with renal cysts. Cyst drainage and alcoholization were achieved without complications in 19 animals, and all clinical signs resolved after the procedure. In three cases, transient bleeding was observed during alcoholization, and the procedure was interrupted. Blood pressure normalized in the four dogs with renal cysts, but it remained elevated in the four cats. PMID- 17339289 TI - Two cases of planned relaparotomy for severe peritonitis secondary to gastrointestinal pathology. AB - Planned relaparotomy is a technique in which two or more surgeries are planned before or during the initial surgery. Two dogs underwent planned relaparotomy for severe peritonitis secondary to gastric ulceration and linear foreign body. Both dogs had good outcomes, and unnecessary procedures that would likely have led to increased morbidity were avoided. This technique may be useful in avoiding unnecessary procedures as well as providing for better stabilization of the animal. PMID- 17339290 TI - Giant hypertrophic gastritis (Menetrier's-like disease) in an Old English sheepdog. AB - An 11-year-old, male Old English sheepdog was admitted for weight loss and intermittent vomiting of 1 month's duration. A cranioventral abdominal mass, anemia, hypoproteinemia, and hypoalbuminemia were the prominent abnormal findings. Imaging studies identified a remarkably thickened gastric wall with multilobulated folds protruding into the gastric lumen. Gastrotomy revealed the presence of giant cerebriform rugal folds arising from the fundus and body of the stomach. Pronounced gastric glandular hyperplasia and lack of evidence of cellular atypia were suggestive of giant hypertrophic gastritis. The dog was treated with prednisolone, cimetidine, and hyoscine butylbromide, only to experience a short-term remission. PMID- 17339291 TI - Surgical correction of colonic duplication in a cat. AB - A 2-year-old, castrated male Manx cat was presented for anorexia, obstipation, and straining to defecate. Imaging tests revealed a cystic mass associated with the descending colon. Three surgical explorations over several years were performed before complete resection of the cystic mass was achieved. Histopathology of the mass revealed normal colonic structures consistent with colonic duplication. Complete resection of a noncommunicating duplicate colon may allow successful treatment of this condition and resolution of associated clinical signs. PMID- 17339292 TI - Epidural spinal myelolipoma in a dog. AB - Epidural spinal myelolipoma was diagnosed in a 13-year-old, male Siberian husky that was referred for evaluation of progressive pelvic limb paresis and urinary incontinence. An epidural mass was detected by magnetic resonance imaging and computed tomography. The mass was removed and identified histopathologically as an epidural myelolipoma. Pelvic limb paresis improved after surgery, but urinary retention associated with neurological bladder dysfunction persisted. PMID- 17339293 TI - Exposure to metals: are we protecting the workers? PMID- 17339294 TI - Farming and prostate cancer. PMID- 17339295 TI - Office work exposures [corrected] and respiratory and sick building syndrome symptoms. AB - OBJECTIVES: To assess the relation between exposure to carbonless copy paper (CCP), paper dust, and fumes from photocopiers and printers (FPP), and the occurrence of sick building syndrome (SBS)-related symptoms, chronic respiratory symptoms and respiratory infections. METHODS: A population-based cross-sectional study with a random sample of 1016 adults, 21-63 years old, living in Pirkanmaa District in South Finland was conducted. This study focused on 342 office workers classified as professionals, clerks or administrative personnel according to their current occupation by the International Standard Classification of Occupations-88. They answered a questionnaire about personal information, health, smoking, occupation, and exposures in the work environment and at home. RESULTS: In logistic regression analyses adjusting for age, sex and a set of other confounders, all three exposures were related to a significantly increased risk of general symptoms (headache and fatigue). Exposure to paper dust and to FPP was associated with upper respiratory and skin symptoms, breathlessness, tonsillitis and middle ear infections. Exposure to CCP increased the risk of eye symptoms, chronic bronchitis and breathlessness. It was also associated with increased occurrence of sinus and middle ear infections and diarrhoea. A dose-response relations was observed between the number of exposures and occurrence of headache. The risk of tonsillitis and sinus infections also increased with increasing number of exposures. All chronic respiratory symptoms, apart from cough, were increased in the highest exposure category (including all three exposures). CONCLUSIONS: This study provides new evidence that exposure to paper dust and to FPP is related to the risk of SBS symptoms, breathlessness and upper respiratory infections. It strengthens the evidence that exposure to CCP increases the risk of eye symptoms, general symptoms, chronic respiratory symptoms and some respiratory infections. Reduction of these exposures could improve the health of office workers. PMID- 17339296 TI - The use of salivary biomarkers in occupational and environmental medicine. PMID- 17339297 TI - Why do managers allocate resources to workplace health promotion programmes in countries with national health coverage? AB - There is extensive evidence that worksite health promotion (WHP) programmes reduce healthcare costs and improve employee productivity. In many countries, a large proportion of healthcare costs are borne by the state. While the full benefits of WHP are still created, they are shared between employers and the state, even though the employer bears the full (after-tax) cost. Employers therefore have a lower incentive to implement WHP activity. We know little about the beliefs of managers with decision responsibility for the approval and implementation of WHP programmes in this context. This article reports the results of a study of the attitudes of Canadian senior general managers (GMs) and human resource managers (HRMs) in the auto parts industry in Ontario, Canada towards the consequences of increasing discretionary spending on WHP, using Structural Equation Modelling and the Theory of Planned Behaviour. We identified factors that explain managers' intentions to increase discretionary spending on wellness programmes. While both senior GMs and HRMs are motivated primarily by their beliefs that WHP reduces indirect costs of health failure, GMs were also motivated by their moral responsibility towards employees (but surprisingly HRMs were not). Importantly, HRMs, who usually have responsibility for WHP, felt constrained by a lack of power to commit resources. Most importantly, we found no social expectation that organizations should provide WHP programmes. This has important implications in an environment where the adoption of WHP is very limited and cost containment within the healthcare system is paramount. PMID- 17339298 TI - Why journals can live without impact factor and cluster bombs. PMID- 17339299 TI - Reed-Elsevier's hypocrisy in selling arms and health. PMID- 17339300 TI - Diabetes epidemic in the South Asian Diaspora: action before desperation. PMID- 17339301 TI - Response to Scientific journals are 'faith based': is there a science behind peer review? PMID- 17339302 TI - Ankle brachial pressure index. PMID- 17339303 TI - The demise of nursing. PMID- 17339304 TI - Feeling the skin. PMID- 17339305 TI - The Falun Gong, organ transplantation, the holocaust and ourselves. PMID- 17339306 TI - Redefining quality of care. PMID- 17339307 TI - The lost hospitals of St Luke's. PMID- 17339308 TI - Oxygen therapy in myocardial infarction: an historical perspective. PMID- 17339309 TI - Key issues in the diagnosis and management of tuberculosis. PMID- 17339310 TI - Life and times of the impact factor: retrospective analysis of trends for seven medical journals (1994-2005) and their Editors' views. AB - OBJECTIVE: (1) To analyse trends in the journal impact factor (IF) of seven general medical journals (Ann Intern Med, BMJ, CMAJ, JAMA, Lancet, Med J Aust and N Engl J Med) over 12 years; and (2) to ascertain the views of these journals' past and present Editors on factors that had affected their journals' IFs during their tenure, including direct editorial policies. DESIGN: Retrospective analysis of IF data from ISI Web of Knowledge Journal Citation Reports-Science Edition, 1994 to 2005, and interviews with Editors-in-Chief. SETTING: Medical journal publishing. PARTICIPANTS: Ten Editors-in-Chief of the journals, except Med J Aust, who served between 1999 and 2004. MAIN OUTCOME MEASURES IFs and component numerator and denominator data for the seven general medical journals (1994 to 2005) were collected. IFs are calculated using the formula: (Citations in year z to articles published in years x and y)/(Number of citable articles published in years x and y), where z is the current year and x and y are the previous two years. Editors' views on factors that had affected their journals' IFs were also obtained. RESULTS: IFs generally rose over the 12-year period, with the N Engl J Med having the highest IF throughout. However, percentage rises in IF relative to the baseline year of 1994 were greatest for CMAJ (about 500%) and JAMA (260%). Numerators for most journals tended to rise over this period, while denominators tended to be stable or to fall, although not always in a linear fashion. Nine of ten eligible editors were interviewed. Possible reasons given for rises in citation counts included: active recruitment of high-impact articles by courting researchers; offering authors better services; boosting the journal's media profile; more careful article selection; and increases in article citations. Most felt that going online had not affected citations. Most had no deliberate policy to publish fewer articles (lowering the IF denominator), which was sometimes the unintended result of other editorial policies. The two Editors who deliberately published fewer articles did so as they realized IFs were important to authors. Concerns about the accuracy of ISI counting for the IF denominator prompted some to routinely check their IF data with ISI. All Editors had mixed feelings about using IFs to evaluate journals and academics, and mentioned the tension between aiming to improve IFs and 'keeping their constituents [clinicians] happy.' CONCLUSIONS: IFs of the journals studied rose in the 12-year period due to rising numerators and/or falling denominators, to varying extents. Journal Editors perceived that this occurred for various reasons, including deliberate editorial practices. The vulnerability of the IF to editorial manipulation and Editors' dissatisfaction with it as the sole measure of journal quality lend weight to the need for complementary measures. PMID- 17339311 TI - Mesalazine-induced bronchiectasis and eosinophilia in a patient with ulcerative colitis: a case report. PMID- 17339312 TI - Withering's 1785 appeal for caution when reporting on a new medicine. PMID- 17339313 TI - Listening, or just hearing what they say? PMID- 17339314 TI - Complementation analysis demonstrates that insulin cross-links both alpha subunits in a truncated insulin receptor dimer. AB - The insulin receptor is a homodimer composed of two alphabeta half receptors. Scanning mutagenesis studies have identified key residues important for insulin binding in the L1 domain (amino acids 1-150) and C-terminal region (amino acids 704-719) of the alpha subunit. However, it has not been shown whether insulin interacts with these two sites within the same alpha chain or whether it cross links a site from each alpha subunit in the dimer to achieve high affinity binding. Here we have tested the contralateral binding mechanism by analyzing truncated insulin receptor dimers (midi-hIRs) that contain complementary mutations in each alpha subunit. Midi-hIRs containing Ala(14), Ala(64), or Gly(714) mutations were fused with Myc or FLAG epitopes at the C terminus and were expressed separately by transient transfection. Immunoblots showed that R14A+FLAG, F64A+FLAG, and F714G+Myc mutant midi-hIRs were expressed in the medium but insulin binding activity was not detected. However, after co-transfection with R14A+FLAG/F714G+Myc or F64A+FLAG/F714G+Myc, hybrid dimers were obtained with a marked increase in insulin binding activity. Competitive displacement assays revealed that the hybrid mutant receptors bound insulin with the same affinity as wild type and also displayed curvilinear Scatchard plots. In addition, when hybrid mutant midi-hIR was covalently cross-linked with (125)I(A14)-insulin and reduced, radiolabeled monomer was immunoprecipitated only with anti-FLAG, demonstrating that insulin was bound asymmetrically. These results demonstrate that a single insulin molecule can contact both alpha subunits in the insulin receptor dimer during high affinity binding and this property may be an important feature for receptor signaling. PMID- 17339315 TI - Non-canonical interaction of phosphoinositides with pleckstrin homology domains of Tiam1 and ArhGAP9. AB - Pleckstrin homology (PH) domains are phosphoinositide (PI)-binding modules that target proteins to membrane surfaces. Here we define a family of PH domain proteins, including Tiam1 and ArhGAP9, that demonstrates specificity for PI(4,5)P(2), as well as for PI(3,4,5)P(3) and PI(3,4)P(2), the products of PI 3 kinase. These PH domain family members utilize a non-canonical phosphoinositide binding pocket related to that employed by beta-spectrin. Crystal structures of the PH domain of ArhGAP9 in complex with the headgroups of Ins(1,3,4)P(3), Ins(1,4,5)P(3), and Ins(1,3,5)P(3) reveal how two adjacent phosphate positions in PI(3,4)P(2), PI(4,5)P(2), and PI(3,4,5)P(3) are accommodated through flipped conformations of the bound phospholipid. We validate the non-canonical site of phosphoinositide interaction by showing that binding pocket mutations, which disrupt phosphoinositide binding in vitro, also disrupt membrane localization of Tiam1 in cells. We posit that the diversity in PI interaction modes displayed by PH domains contributes to their versatility of use in biological systems. PMID- 17339316 TI - Consequences of direct versus indirect activation of epidermal growth factor receptor in intestinal epithelial cells are dictated by protein-tyrosine phosphatase 1B. AB - The epidermal growth factor receptor (EGFR) is an integral regulator of many cellular functions. EGFR also acts as a central conduit for extracellular signals involving direct activation of the receptor by EGFR ligands or indirect activation by G protein-coupled receptor (GPCR)-stimulated transactivation of the EGFR. We have previously shown that EGFR negatively regulates epithelial chloride secretion as a result of transforming growth factor-alpha-mediated EGFR transactivation in response to muscarinic GPCR activation. Here we show that direct activation of the EGFR by EGFR ligands produces a different pattern of EGFR tyrosine phosphorylation and downstream phosphatidylinositol 3-kinase recruitment than GPCR-stimulated transactivation of the EGFR occurring via paracrine EGFR ligand release. Moreover, we demonstrate that this differential signaling and its consequences depend on protein-tyrosine phosphatase 1B activity. Thus protein-tyrosine phosphatase 1B governs differential recruitment of signaling pathways involved in EGFR regulation of epithelial ion transport. Our findings furthermore establish how divergent signaling outcomes can arise from the activation of a single receptor. PMID- 17339317 TI - Loss of secretory pathway FK506-binding proteins results in cold-sensitive lethality and associate extracellular matrix defects in the nematode Caenorhabditis elegans. AB - The FK506-binding proteins (FKBs) represent ubiquitous enzymes that catalyze the rate-limiting peptidyl prolyl cis-trans isomerization step in protein folding. The nematode Caenorhabditis elegans has eight FKBs, three of which (FKB-3, -4, and -5) have dual peptidyl prolyl cis-trans isomerase (PPIase) domains, signal peptides and ER retention signals. PPIase activity has been detected for recombinant FKB-3. Both FKB-3 and -5 are expressed in the exoskeleton synthesizing hypodermis with transcript peaks that correspond to the molting and collagen synthesis cycles. FKB-4 is expressed at a low level throughout development. No phenotypes were observed in deletion mutants in each of the secretory pathway FKBs. Combined triple and fkb-4, -5 double deletion mutants were however found to arrest at 12 degrees C, but developed normally at 15-25 degrees C. This cold-sensitive larval lethal effect was not maternally derived, occurred during embryogenesis, and could be rescued following the transgenic introduction of a wild type copy of either fkb-4 or fkb-5. The temperature sensitive defects also affected molting, cuticle collagen expression, hypodermal seam cell morphology, and the structural integrity of the cuticular extracellular matrix. This study establishes that the secretory pathway FK506-binding PPIase enzymes are essential for normal nematode development, collagen biogenesis, and the formation of an intact exoskeleton under adverse physiological conditions. PMID- 17339318 TI - Interaction of hydroxylated collagen IV with the von hippel-lindau tumor suppressor. AB - The von Hippel-Lindau tumor suppressor (pVHL) targets hydroxylated alpha-subunits of hypoxia-inducible factor (HIF) for ubiquitin-mediated proteasomal destruction through direct interaction with the hydroxyproline binding pocket in its beta domain. Although disruption of this process may contribute to VHL-associated tumor predisposition by up-regulation of HIF target genes, genetic and biochemical analyses support the existence of additional functions, including a role in the assembly of extracellular matrix. In an attempt to delineate these pathways, we searched for novel pVHL-binding proteins. Here we report a direct, hydroxylation-dependent interaction with alpha-chains of collagen IV. Interaction with pVHL was also observed with fibrillar collagen chains, but not the folded collagen triple helix. The interaction was suppressed by a wide range of tumor associated mutations, including those that do not disturb the regulation of HIF, supporting a role in HIF-independent tumor suppressor functions. PMID- 17339319 TI - In vivo and in vitro analyses of single-amino acid variants of the Salmonella enterica phosphotransacetylase enzyme provide insights into the function of its N terminal domain. AB - The function of the N-terminal domain ( approximately 350 residues) of the Pta (phosphotransacetylase) enzyme of Salmonella enterica is unclear. Results from in vivo genetic and in vitro studies suggest that the N-terminal domain of Pta is a sensor for NADH and pyruvate. We isolated 10 single-amino acid variants of Pta that, unlike the wild-type protein, supported growth of a strain of S. enterica devoid of Acs (acetyl-CoA synthetase; AMP-forming) activity on 10 mm acetate. All mutations were mapped within the N-terminal domain of the protein. Kinetic analyses of the wild type and three variant Pta proteins showed that two of the variant proteins were faster enzymes (k(cat) 2.5-3-fold > k(cat) Pta(WT). Results from sedimentation equilibrium experiments are consistent with Pta(WT) being a trimer. Pta variants formed more hexamer than the Pta(WT) protein. NADH inhibited Pta(WT) activity by inducing a conformational change detectable by limited trypsin proteolysis; NADH did not inhibit variant protein Pta(R252H). Pyruvate stimulated Pta(WT) activity, and its effect was potentiated in the variants, being most pronounced on Pta(R252H). PMID- 17339320 TI - Disabled-2 is an epithelial surface positioning gene. AB - The formation of the primitive endoderm layer on the surface of the inner cell mass is one of the earliest epithelial morphogenesis in mammalian embryos. In mouse embryos deficient of Disabled-2 (Dab2), the primitive endoderm cells lose the ability to position on the surface, resulting in defective morphogenesis. Embryonic stem cells lacking Dab2 are also unable to position on the surface of cell aggregates and fail to form a primitive endoderm outer layer in the embryoid bodies. The cellular function of Dab2, a cargo-selective adaptor, in mediating endocytic trafficking of clathrin-coated vesicles is well established. We show here that Dab2 mediates directional trafficking and polarized distribution of cell surface proteins such as megalin and E-cadherin and propose that loss of polarity is the underlying mechanism for the loss of epithelial cell surface positioning in Dab2-deficient embryos and embryoid bodies. Thus, the findings indicate that Dab2 is a surface positioning gene and suggest a novel mechanism of epithelial cell surface targeting. PMID- 17339321 TI - Molecular interactions of the gating modifier toxin ProTx-II with NaV 1.5: implied existence of a novel toxin binding site coupled to activation. AB - Voltage-gated Na(+) channels are critical components in the generation of action potentials in excitable cells, but despite numerous structure-function studies on these proteins, their gating mechanism remains unclear. Peptide toxins often modify channel gating, thereby providing a great deal of information about these channels. ProTx-II is a 30-amino acid peptide toxin from the venom of the tarantula, Thrixopelma pruriens, that conforms to the inhibitory cystine knot motif and which modifies activation kinetics of Na(v) and Ca(v), but not K(v), channels. ProTx-II inhibits current by shifting the voltage dependence of activation to more depolarized potentials and, therefore, differs from the classic site 4 toxins that shift voltage dependence of activation in the opposite direction. Despite this difference in functional effects, ProTx-II has been proposed to bind to neurotoxin site 4 because it modifies activation. Here, we investigate the bioactive surface of ProTx-II by alanine-scanning the toxin and analyzing the interactions of each mutant with the cardiac isoform, Na(v)1.5. The active face of the toxin is largely composed of hydrophobic and cationic residues, joining a growing group of predominantly K(v) channel gating modifier toxins that are thought to interact with the lipid environment. In addition, we performed extensive mutagenesis of Na(v)1.5 to locate the receptor site with which ProTx-II interacts. Our data establish that, contrary to prior assumptions, ProTx-II does not bind to the previously characterized neurotoxin site 4, thus making it a novel probe of activation gating in Na(v) channels with potential to shed new light on this process. PMID- 17339322 TI - Loss of phylloquinone in Chlamydomonas affects plastoquinone pool size and photosystem II synthesis. AB - Phylloquinone functions as the electron transfer cofactor at the A(1) site of photosystem I. We have isolated and characterized a mutant of Chlamydomonas reinhardtii, menD1, that is deficient in MenD, which encodes 2-succinyl-6-hydroxy 2,4-cyclohexadiene-1-carboxylate synthase, an enzyme that catalyzes the first specific step of the phylloquinone biosynthetic pathway. The mutant is photosynthetically active but light-sensitive. Analysis of total pigments by mass spectrometry reveals that phylloquinone is absent in menD1, but plastoquinone levels are not affected. This is further confirmed by the rescue of menD1 by addition of phylloquinone to the growth medium. Analysis of electron transfer by absorption spectroscopy indicates that plastoquinone replaces phylloquinone in photosystem I and that electron transfer from A(1) to the iron-sulfur centers is slowed down at least 40-fold. Consistent with a replacement of phylloquinone by plastoquinone, the size of the free plastoquinone pool of menD1 is reduced by 20 30%. In contrast to cyanobacterial MenD-deficient mutants, photosystem I accumulates normally in menD1, whereas the level of photosystem II declines. This decrease is because of reduced synthesis of the photosystem II core subunits. The relationship between plastoquinone occupancy of the A(1) site in photosystem I and the reduced accumulation of photosystem II is discussed. PMID- 17339323 TI - Classical anticytokinins do not interact with cytokinin receptors but inhibit cyclin-dependent kinases. AB - Cytokinins are a class of plant hormones that regulate the cell cycle and diverse developmental and physiological processes. Several compounds have been identified that antagonize the effects of cytokinins. Based on structural similarities and competitive inhibition, it has been assumed that these anticytokinins act through a common cellular target, namely the cytokinin receptor. Here, we examined directly the possibility that various representative classical anticytokinins inhibit the Arabidopsis cytokinin receptors CRE1/AHK4 (cytokinin response 1/Arabidopsis histidine kinase 4) and AHK3 (Arabidopsis histidine kinase 3). We show that pyrrolo[2,3-d]pyrimidine and pyrazolo[4,3-d]pyrimidine anticytokinins do not act as competitors of cytokinins at the receptor level. Flow cytometry and microscopic analyses revealed that anticytokinins inhibit the cell cycle and cause disorganization of the microtubular cytoskeleton and apoptosis. This is consistent with the hypothesis that they inhibit regulatory cyclin-dependent kinase (CDK) enzymes. Biochemical studies demonstrated inhibition by selected anti-cytokinins of both Arabidopsis and human CDKs. X-ray determination of the crystal structure of a human CDK2-anticytokinin complex demonstrated that the antagonist occupies the ATP-binding site of CDK2. Finally, treatment of human cancer cell lines with anticytokinins demonstrated their ability to kill human cells with similar effectiveness as known CDK inhibitors. PMID- 17339324 TI - The C-type lectin receptors CLEC-2 and Dectin-1, but not DC-SIGN, signal via a novel YXXL-dependent signaling cascade. AB - The two lectin receptors, CLEC-2 and Dectin-1, have been shown to signal through a Syk-dependent pathway, despite the presence of only a single YXXL in their cytosolic tails. In this study, we show that stimulation of CLEC-2 in platelets and in two mutant cell lines is dependent on the YXXL motif and on proteins that participate in signaling by immunoreceptor tyrosine-based activation motif receptors, including Src, Syk, and Tec family kinases, and on phospholipase Cgamma. Strikingly, mutation of either Src homology (SH) 2 domain of Syk blocks signaling by CLEC-2 despite the fact that it has only a single YXXL motif. Furthermore, signaling by CLEC-2 is only partially dependent on the BLNK/SLP-76 family of adapter proteins in contrast to that of immunoreceptor tyrosine-based activation motif receptors. The C-type lectin receptor, Dectin-1, which contains a YXXL motif preceded by the same four amino acids as for CLEC-2 (DEDG), signals like CLEC-2 and also requires the two SH2 domains of Syk and is only partially dependent on the BLNK/SLP-76 family of adapters. In marked contrast, the C-type lectin receptor, DC-SIGN, which has a distinct series of amino acids preceding a single YXXL, signals independent of this motif. A mutational analysis of the DEDG sequence of CLEC-2 revealed that the glycine residue directly upstream of the YXXL tyrosine is important for CLEC-2 signaling. These results demonstrate that CLEC-2 and Dectin-1 signal through a single YXXL motif that requires the tandem SH2 domains of Syk but is only partially dependent on the SLP-76/BLNK family of adapters. PMID- 17339325 TI - Structural and functional properties of a truncated hemoglobin from a food-borne pathogen Campylobacter jejuni. AB - Campylobacter jejuni contains two hemoglobins, Cgb and Ctb. Cgb has been suggested to perform an NO detoxification reaction to protect the bacterium against NO attack. On the other hand, the physiological function of Ctb, a class III truncated hemoglobin, remains unclear. By using CO as a structural probe, resonance Raman data show that the distal heme pocket of Ctb exhibits a positive electrostatic potential. In addition, two ligand-related vibrational modes, nu(Fe O(2)) and nu(O-O), were identified in the oxy derivative, with frequencies at 542 and 1132 cm(-1), respectively, suggesting the presence of an intertwined H bonding network surrounding the heme-bound ligand, which accounts for its unusually high oxygen affinity (222 microm(-1)). Mutagenesis studies of various distal mutants suggest that the heme-bound dioxygen is stabilized by H-bonds donated from the Tyr(B10) and Trp(G8) residues, which are highly conserved in the class III truncated hemoglobins; furthermore, an additional H-bond donated from the His(E7) to the Tyr(B10) further regulates these H-bonding interactions by restricting the conformational freedom of the phenolic side chain of the Tyr(B10). Taken together, the data suggest that it is the intricate balance of the H-bonding interactions that determines the unique ligand binding properties of Ctb. The extremely high oxygen affinity of Ctb makes it unlikely to function as an oxygen transporter; on the other hand, the distal heme environment of Ctb is surprisingly similar to that of cytochrome c peroxidase, suggesting a role of Ctb in performing a peroxidase or P450-type of oxygen chemistry. PMID- 17339326 TI - Kruppel-like factor 4 regulates endothelial inflammation. AB - The vascular endothelium plays a critical role in vascular homeostasis. Inflammatory cytokines and non-laminar blood flow induce endothelial dysfunction and confer a pro-adhesive and pro-thrombotic phenotype. Therefore, identification of factors that mediate the effects of these stimuli on endothelial function is of considerable interest. Kruppel-like factor 4 expression has been documented in endothelial cells, but a function has not been described. In this communication we describe the expression in vitro and in vivo of Kruppel-like factor 4 in human and mouse endothelial cells. Furthermore, we demonstrate that endothelial Kruppel like factor 4 is induced by pro-inflammatory stimuli and shear stress. Overexpression of Kruppel-like factor 4 induces expression of multiple anti inflammatory and anti-thrombotic factors including endothelial nitric-oxide synthase and thrombomodulin, whereas knockdown of Kruppellike factor 4 leads to enhancement of tumor necrosis factor alpha-induced vascular cell adhesion molecule-1 and tissue factor expression. The functional importance of Kruppel like factor 4 is verified by demonstrating that Kruppel-like factor 4 expression markedly decreases inflammatory cell adhesion to the endothelial surface and prolongs clotting time under inflammatory states. Kruppel-like factor 4 differentially regulates the promoter activity of pro- and anti-inflammatory genes in a manner consistent with its anti-inflammatory function. These data implicate Kruppel-like factor 4 as a novel regulator of endothelial activation in response to pro-inflammatory stimuli. PMID- 17339327 TI - Genome-wide analysis of histone lysine methylation variations caused by diabetic conditions in human monocytes. AB - Aberrant histone lysine methylation patterns that change chromatin structure can promote dysregulated gene transcription and disease progression. Diabetic conditions such as high glucose (HG) are known to alter key pathologic pathways. However, their impact on cellular histone lysine methylation is unknown. We hypothesized that chronic HG can induce aberrant changes in histone H3 lysine 4 and lysine 9 dimethylation (H3K4me2 and H3K9me2) within target cells. Chromatin immunoprecipitation linked to microarrays (ChIP-on-chip) is currently a widely used approach for acquiring genome-wide information on histone modifications. We adopted this approach to profile and compare the variations in H3K4me2 and H3K9me2 in human gene coding and CpG island regions in THP-1 monocytes cultured in normal glucose and HG. Subsequently, we identified key relevant candidate genes displaying differential changes in H3K4me2 and H3K9me2 in HG versus normal glucose and also validated them with follow-up conventional ChIPs. Relevance to human diabetes was demonstrated by noting that H3K9me2 at the coding and promoter regions of two candidate genes was significantly greater in blood monocytes of diabetic patients relative to normal controls similar to the THP-1 data. In addition, regular mRNA profiling with cDNA arrays revealed correlations between mRNA and H3K9me2 levels. These novel results show histone methylation variations, for the first time, under diabetic conditions at a genome-wide level. PMID- 17339328 TI - Novel role for mitochondria: protein kinase Ctheta-dependent oxidative signaling organelles in activation-induced T-cell death. AB - Reactive oxygen species (ROS) play a key role in regulation of activation-induced T-cell death (AICD) by induction of CD95L expression. However, the molecular source and the signaling steps necessary for ROS production are largely unknown. Here, we show that the proximal T-cell receptor-signaling machinery, including ZAP70 (zeta chain-associated protein kinase 70), LAT (linker of activated T cells), SLP76 (SH2 domain-containing leukocyte protein of 76 kDa), PLCgamma1 (phospholipase Cgamma1), and PKCtheta (protein kinase Ctheta), are crucial for ROS production. PKCtheta is translocated to the mitochondria. By using cells depleted of mitochondrial DNA, we identified the mitochondria as the source of activation-induced ROS. Inhibition of mitochondrial electron transport complex I assembly by small interfering RNA (siRNA)-mediated knockdown of the chaperone NDUFAF1 resulted in a block of ROS production. Complex I-derived ROS are converted into a hydrogen peroxide signal by the mitochondrial superoxide dismutase. This signal is essential for CD95L expression, as inhibition of complex I assembly by NDUFAF1-specific siRNA prevents AICD. Similar results were obtained when metformin, an antidiabetic drug and mild complex I inhibitor, was used. Thus, we demonstrate for the first time that PKCtheta-dependent ROS generation by mitochondrial complex I is essential for AICD. PMID- 17339329 TI - The polycomb group protein Suz12 is required for embryonic stem cell differentiation. AB - Polycomb group (PcG) proteins form multiprotein complexes, called Polycomb repressive complexes (PRCs). PRC2 contains the PcG proteins EZH2, SUZ12, and EED and represses transcription through methylation of lysine (K) 27 of histone H3 (H3). Suz12 is essential for PRC2 activity and its inactivation results in early lethality of mouse embryos. Here, we demonstrate that Suz12(-/-) mouse embryonic stem (ES) cells can be established and expanded in tissue culture. The Suz12(-/-) ES cells are characterized by global loss of H3K27 trimethylation (H3K27me3) and higher expression levels of differentiation-specific genes. Moreover, Suz12(-/-) ES cells are impaired in proper differentiation, resulting in a lack of repression of ES cell markers as well as activation of differentiation-specific genes. Finally, we demonstrate that the PcGs are actively recruited to several genes during ES cell differentiation, which despite an increase in H3K27me3 levels is not always sufficient to prevent transcriptional activation. In summary, we demonstrate that Suz12 is required for the establishment of specific expression programs required for ES cell differentiation. Furthermore, we provide evidence that PcGs have different mechanisms to regulate transcription during cellular differentiation. PMID- 17339330 TI - DNA repair and transcriptional deficiencies caused by mutations in the Drosophila p52 subunit of TFIIH generate developmental defects and chromosome fragility. AB - The transcription and DNA repair factor TFIIH is composed of 10 subunits. Mutations in the XPB, XPD, and p8 subunits are genetically linked to human diseases, including cancer. However, no reports of mutations in other TFIIH subunits have been reported in higher eukaryotes. Here, we analyze at genetic, molecular, and biochemical levels the Drosophila melanogaster p52 (DMP52) subunit of TFIIH. We found that DMP52 is encoded by the gene marionette in Drosophila and that a defective DMP52 produces UV light-sensitive flies and specific phenotypes during development: organisms are smaller than their wild-type siblings and present tumors and chromosomal instability. The human homologue of DMP52 partially rescues some of these phenotypes. Some of the defects observed in the fly caused by mutations in DMP52 generate trichothiodystrophy and cancer-like phenotypes. Biochemical analysis of DMP52 point mutations introduced in human p52 at positions homologous to those of defects in DMP52 destabilize the interaction between p52 and XPB, another TFIIH subunit, thus compromising the assembly of the complex. This study significantly extends the role of p52 in regulating XPB ATPase activity and, consequently, both its transcriptional and nucleotide excision repair functions. PMID- 17339331 TI - An activating mutation in sos-1 identifies its Dbl domain as a critical inhibitor of the epidermal growth factor receptor pathway during Caenorhabditis elegans vulval development. AB - Proper regulation of receptor tyrosine kinase (RTK)-Ras-mitogen-activated protein kinase (MAPK) signaling pathways is critical for normal development and the prevention of cancer. SOS is a dual-function guanine nucleotide exchange factor (GEF) that catalyzes exchange on Ras and Rac. Although the physiologic role of SOS and its CDC25 domain in RTK-mediated Ras activation is well established, the in vivo function of its Dbl Rac GEF domain is less clear. We have identified a novel gain-of-function missense mutation in the Dbl domain of Caenorhabditis elegans SOS-1 that promotes epidermal growth factor receptor (EGFR) signaling in vivo. Our data indicate that a major developmental function of the Dbl domain is to inhibit EGF-dependent MAPK activation. The amount of inhibition conferred by the Dbl domain is equal to that of established trans-acting inhibitors of the EGFR pathway, including c-Cbl and RasGAP, and more than that of MAPK phosphatase. In conjunction with molecular modeling, our data suggest that the C. elegans mutation, as well as an equivalent mutation in human SOS1, activates the MAPK pathway by disrupting an autoinhibitory function of the Dbl domain on Ras activation. Our work suggests that functionally similar point mutations in humans could directly contribute to disease. PMID- 17339332 TI - Rct1, a nuclear RNA recognition motif-containing cyclophilin, regulates phosphorylation of the RNA polymerase II C-terminal domain. AB - Phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAP II) is a dynamic process that regulates transcription and coordinates it with pre-mRNA processing. We show here that Rct1, a nuclear multidomain cyclophilin from Schizosaccharomyces pombe, is encoded by an essential gene that interacts with the CTD and regulates its phosphorylation in vivo. Downregulation of Rct1 levels results in increased phosphorylation of the CTD at both Ser2 and Ser5 and in a commensurate decrease in RNAP II transcription. In contrast, overexpression of Rct1 decreases phosphorylation on both sites. The close association of Rct1 with transcriptionally active chromatin suggests a role in regulation of RNAP II transcriptional activity. These data, together with the pleiotropic phenotype upon Rct1 deregulation, suggest that this multidomain cyclophilin is an important player in maintaining the correct phosphorylation code of the CTD and thereby regulating CTD function. PMID- 17339333 TI - Constitutive turnover of cyclin E by Cul3 maintains quiescence. AB - Two distinct pathways for the degradation of mammalian cyclin E have previously been described. One pathway is induced by cyclin E phosphorylation and is dependent on the Cul1/Fbw7-based E3 ligase. The other pathway is dependent on the Cul3-based E3 ligase, but the mechanistic details of this pathway have yet to be elucidated. To establish the role of Cul3 in the degradation of cyclin E in vivo, we created a conditional knockout of the Cul3 gene in mice. Interestingly, the biallelic loss of Cul3 in primary fibroblasts derived from these mice results in increased cyclin E expression and reduced cell viability, paralleling the loss of Cul3 protein expression. Cell cycle analysis of viable, Cul3 hypomorphic cells shows that decreasing the levels of Cul3 increases both cyclin E protein levels and the number of cells in S phase. In order to examine the role of Cul3 in an in vivo setting, we determined the effect of deletion of the Cul3 gene in liver. This gene deletion resulted in a dramatic increase in cyclin E levels as well as an increase in cell size and ploidy. The results we report here show that the constitutive degradation pathway for cyclin E that is regulated by the Cul3-based E3 ligase is essential to maintain quiescence in mammalian cells. PMID- 17339334 TI - The nucleosome assembly activity of NAP1 is enhanced by Alien. AB - The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitamin D receptor (VDR), binds in vivo and in vitro to NAP1 and modulates its activity by enhancing NAP1-mediated nucleosome assembly on DNA. Furthermore, Alien reduces the accessibility of the histones H3 and H4 for NAP1-promoted assembly reaction. This indicates that Alien sustains and reinforces the formation of nucleosomes. Employing deletion mutants of Alien suggests that different regions of Alien are involved in enhancement of NAP1 mediated nucleosome assembly and in inhibiting the accessibility of the histones H3 and H4. In addition, we provide evidence that Alien is associated with chromatin and with micrococcus nuclease-prepared nucleosome fractions and interacts with the histones H3 and H4. Furthermore, chromatin immunoprecipitation and reimmunoprecipitation experiments suggest that NAP1 and Alien localize to the endogenous CYP24 promoter in vivo, a VDR target gene. Based on these findings, we present here a novel pathway linking corepressor function with nucleosome assembly activity. PMID- 17339335 TI - Thymomegaly, microsplenia, and defective homeostatic proliferation of peripheral lymphocytes in p51-Ets1 isoform-specific null mice. AB - Ets1 is a member of the Ets transcription factor family. Alternative splicing of exon VII results in two naturally occurring protein isoforms: full-length Ets1 (p51-Ets1) and Ets1(DeltaVII) (p42-Ets1). These isoforms bear key distinctions regarding protein-protein interactions, DNA binding kinetics, and transcriptional target specificity. Disruption of both Ets1 isoforms in mice results in the loss of detectable NK and NKT cell activity and defects in B and T lymphocytes. We generated mice that express only the Ets1(DeltaVII) isoform. Ets1(DeltaVII) homozygous mice express no p51-Ets1 and elevated levels of the p42-Ets1 protein relative to the wild type and display increased perinatal lethality, thymomegaly, and peripheral lymphopenia. Proliferation was increased in both the thymus and the spleen, while apoptosis was decreased in the thymus and increased in the spleen of homozygotes. Significant elevations of CD8(+) and CD8(+)CD4(+) thymocytes were observed. Lymphoid cell (CD19(+), CD4(+), and CD8(+)) reductions were predominantly responsible for diminished spleen cellularity, with fewer memory cells and a failure of homeostatic proliferation to maintain peripheral lymphocytes. Collectively, the Ets1(DeltaVII) mutants demonstrate lymphocyte maturation defects associated with misregulation of p16(Ink4a), p27(Kip1), and CD44. Thus, a balance in the differential regulation of Ets1 isoforms represents a potential mechanism in the control of lymphoid maturation and homeostasis. PMID- 17339336 TI - Functional and physical interactions between yeast 14-3-3 proteins, acetyltransferases, and deacetylases in response to DNA replication perturbations. AB - The highly conserved 14-3-3 proteins participate in many biological processes in different eukaryotes. The BMH1 and BMH2 genes encode the two functionally redundant Saccharomyces cerevisiae 14-3-3 isoforms. In this work we provide evidence that defective 14-3-3 functions not only impair the ability of yeast cells to sustain DNA replication in the presence of sublethal concentrations of methyl methanesulfonate (MMS) or hydroxyurea (HU) but also cause S-phase checkpoint hyperactivation. Inactivation of the catalytic subunit of the histone acetyltransferase NuA4 or of its interactor Yng2, besides leading to S-phase defects and persistent checkpoint activation in the presence of genotoxic agents, is lethal for bmh mutants. Conversely, the lack of the histone deacetylase subunit Rpd3 or Sin3 partially suppresses the hypersensitivity to HU of bmh mutants and restores their ability to complete DNA replication in the presence of MMS or HU. These data strongly suggest that reduced acetyltransferase functionality might account for the S-phase defects of bmh mutants in the presence of genotoxic agents. Consistent with a role of 14-3-3 proteins in acetyltransferase and deacetylase regulation, we find that acetylation of H3 and H4 histone tails is reduced in temperature-sensitive bmh mutants shifted to the restrictive temperature. Moreover, Bmh proteins physically interact, directly or indirectly, with the Esa1 acetyltransferase throughout the cell cycle and with the Rpd3 deacetylase specifically during unperturbed S phase and after HU treatment. Taken together, our results highlight a novel role for 14-3-3 proteins in the regulation of histone acetyltransferase and deacetylase functions in the response to replicative stress. PMID- 17339337 TI - The MDM2 ubiquitination signal in the DNA-binding domain of p53 forms a docking site for calcium calmodulin kinase superfamily members. AB - Genetic and biochemical studies have shown that Ser(20) phosphorylation in the transactivation domain of p53 mediates p300-catalyzed DNA-dependent p53 acetylation and B-cell tumor suppression. However, the protein kinases that mediate this modification are not well defined. A cell-free Ser(20) phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including CHK2, CHK1, DAPK-1, DAPK-3, DRAK 1, and AMPK, as Ser(20) kinases. Phosphorylation of a p53 transactivation domain fragment at Ser(20) by these enzymes in vitro can be mediated in trans by a docking site peptide derived from the BOX-V domain of p53, which also harbors the ubiquitin signal for MDM2. Evaluation of these calcium calmodulin kinase superfamily members as candidate Ser(20) kinases in vivo has shown that only CHK1 or DAPK-1 can stimulate p53 transactivation and induce Ser(20) phosphorylation of p53. Using CHK1 as a prototypical in vivo Ser(20) kinase, we demonstrate that (i) CHK1 protein depletion using small interfering RNA can attenuate p53 phosphorylation at Ser(20), (ii) an enhanced green fluorescent protein (EGFP)-BOX V fusion peptide can attenuate Ser(20) phosphorylation of p53 in vivo, (iii) the EGFP-BOX-V fusion peptide can selectively bind to CHK1 in vivo, and (iv) the Deltap53 spliced variant lacking the BOX-V motif is refractory to Ser(20) phosphorylation by CHK1. These data indicate that the BOX-V motif of p53 has evolved the capacity to bind to enzymes that mediate either p53 phosphorylation or ubiquitination, thus controlling the specific activity of p53 as a transcription factor. PMID- 17339338 TI - Integrin alpha1beta1 controls reactive oxygen species synthesis by negatively regulating epidermal growth factor receptor-mediated Rac activation. AB - Integrins control many cell functions, including generation of reactive oxygen species (ROS) and regulation of collagen synthesis. Mesangial cells, found in the glomerulus of the kidney, are able to produce large amounts of ROS via the NADPH oxidase. We previously demonstrated that integrin alpha1-null mice develop worse fibrosis than wild-type mice following glomerular injury and this is due, in part, to excessive ROS production by alpha1-null mesangial cells. In the present studies, we describe the mechanism whereby integrin alpha1-null mesangial cells produce excessive ROS. Integrin alpha1-null mesangial cells have constitutively increased basal levels of activated Rac1, which result in its increased translocation to the cell membrane, excessive ROS production, and consequent collagen IV deposition. Basal Rac1 activation is a direct consequence of ligand independent increased epidermal growth factor receptor (EGFR) phosphorylation in alpha1-null mesangial cells. Thus, our study demonstrates that integrin alpha1beta1-EGFR cross talk is a key step in negatively regulating Rac1 activation, ROS production, and excessive collagen synthesis, which is a hallmark of diseases characterized by irreversible fibrosis. PMID- 17339339 TI - mRNAs encoding polarity and exocytosis factors are cotransported with the cortical endoplasmic reticulum to the incipient bud in Saccharomyces cerevisiae. AB - Polarized growth in the budding yeast Saccharomyces cerevisiae depends upon the asymmetric localization and enrichment of polarity and secretion factors at the membrane prior to budding. We examined how these factors (i.e., Cdc42, Sec4, and Sro7) reach the bud site and found that their respective mRNAs localize to the tip of the incipient bud prior to nuclear division. Asymmetric mRNA localization depends upon factors that facilitate ASH1 mRNA localization (e.g., the 3' untranslated region, She proteins 1 to 5, Puf6, actin cytoskeleton, and a physical association with She2). mRNA placement precedes protein enrichment and subsequent bud emergence, implying that mRNA localization contributes to polarization. Correspondingly, mRNAs encoding proteins which are not asymmetrically distributed (i.e., Snc1, Mso1, Tub1, Pex3, and Oxa1) are not polarized. Finally, mutations which affect cortical endoplasmic reticulum (ER) entry and anchoring in the bud (myo4Delta, sec3Delta, and srp101) also affect asymmetric mRNA localization. Bud-localized mRNAs, including ASH1, were found to cofractionate with ER microsomes in a She2- and Sec3-dependent manner; thus, asymmetric mRNA transport and cortical ER inheritance are connected processes in yeast. PMID- 17339340 TI - Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members. AB - Unique among fibroblast growth factors (FGFs), FGF19, -21, and -23 act in an endocrine fashion to regulate energy, bile acid, glucose, lipid, phosphate, and vitamin D homeostasis. These FGFs require the presence of Klotho/betaKlotho in their target tissues. Here, we present the crystal structures of FGF19 alone and FGF23 in complex with sucrose octasulfate, a disaccharide chemically related to heparin. The conformation of the heparin-binding region between beta strands 10 and 12 in FGF19 and FGF23 diverges completely from the common conformation adopted by paracrine-acting FGFs. A cleft between this region and the beta1-beta2 loop, the other heparin-binding region, precludes direct interaction between heparin/heparan sulfate and backbone atoms of FGF19/23. This reduces the heparin binding affinity of these ligands and confers endocrine function. Klotho/betaKlotho have evolved as a compensatory mechanism for the poor ability of heparin/heparan sulfate to promote binding of FGF19, -21, and -23 to their cognate receptors. PMID- 17339341 TI - Analysis of the H19ICR insulator. AB - Transcriptional insulators are specialized cis-acting elements that protect promoters from inappropriate activation by distal enhancers. The H19 imprinting control region (ICR) functions as a CTCF-dependent, methylation-sensitive transcriptional insulator. We analyzed several insertional mutations and demonstrate that the ICR can function as a methylation-regulated maternal chromosome-specific insulator in novel chromosomal contexts. We used chromosome conformation capture and chromatin immunoprecipitation assays to investigate the configuration of cis-acting elements at these several insertion sites. By comparing maternal and paternal organizations on wild-type and mutant chromosomes, we hoped to identify mechanisms for ICR insulator function. We found that promoter and enhancer elements invariably associate to form DNA loop domains at transcriptionally active loci. Conversely, active insulators always prevent these promoter-enhancer interactions. Instead, the ICR insulator forms novel loop domains by associating with the blocked promoters and enhancers. We propose that these associations are fundamental to insulator function. PMID- 17339342 TI - Functional importance of the anaphase-promoting complex-Cdh1-mediated degradation of TMAP/CKAP2 in regulation of spindle function and cytokinesis. AB - Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein (TMAP), is a novel microtubule-associated protein that is frequently upregulated in various malignances. However, its cellular functions remain unknown. A previous study has shown that its protein level begins to increase during G(1)/S and peaks at G(2)/M, after which it decreases abruptly. Ectopic overexpression of TMAP/CKAP2 induced microtubule bundling related to increased microtubule stability. TMAP/CKAP2 overexpression also resulted in cell cycle arrest during mitosis due to a defect in centrosome separation and subsequent formation of a monopolar spindle. We also show that degradation of TMAP/CKAP2 during mitotic exit is mediated by the anaphase promoting complex bound to Cdh1 and that the KEN box motif near the N terminus is necessary for its destruction. Compared to the wild type, expression of a nondegradable mutant of TMAP/CKAP2 significantly increased the occurrence of spindle defects and cytokinesis failure. These results suggest that TMAP/CKAP2 plays a role in the assembly and maintenance of mitotic spindles, presumably by regulating microtubule dynamics, and its destruction during mitotic exit serves an important role in the completion of cytokinesis and in the maintenance of spindle bipolarity in the next mitosis. PMID- 17339344 TI - Insulin stimulates membrane fusion and GLUT4 accumulation in clathrin coats on adipocyte plasma membranes. AB - Total internal reflection fluorescence (TIRF) microscopy reveals highly mobile structures containing enhanced green fluorescent protein-tagged glucose transporter 4 (GLUT4) within a zone about 100 nm beneath the plasma membrane of 3T3-L1 adipocytes. We developed a computer program (Fusion Assistant) that enables direct analysis of the docking/fusion kinetics of hundreds of exocytic fusion events. Insulin stimulation increases the fusion frequency of exocytic GLUT4 vesicles by approximately 4-fold, increasing GLUT4 content in the plasma membrane. Remarkably, insulin signaling modulates the kinetics of the fusion process, decreasing the vesicle tethering/docking duration prior to membrane fusion. In contrast, the kinetics of GLUT4 molecules spreading out in the plasma membrane from exocytic fusion sites is unchanged by insulin. As GLUT4 accumulates in the plasma membrane, it is also immobilized in punctate structures on the cell surface. A previous report suggested these structures are exocytic fusion sites (Lizunov et al., J. Cell Biol. 169:481-489, 2005). However, two-color TIRF microscopy using fluorescent proteins fused to clathrin light chain or GLUT4 reveals these structures are clathrin-coated patches. Taken together, these data show that insulin signaling accelerates the transition from docking of GLUT4 containing vesicles to their fusion with the plasma membrane and promotes GLUT4 accumulation in clathrin-based endocytic structures on the plasma membrane. PMID- 17339343 TI - Function of a conserved checkpoint recruitment domain in ATRIP proteins. AB - The ATR (ATM and Rad3-related) kinase is essential to maintain genomic integrity. ATR is recruited to DNA lesions in part through its association with ATR interacting protein (ATRIP), which in turn interacts with the single-stranded DNA binding protein RPA (replication protein A). In this study, a conserved checkpoint protein recruitment domain (CRD) in ATRIP orthologs was identified by biochemical mapping of the RPA binding site in combination with nuclear magnetic resonance, mutagenesis, and computational modeling. Mutations in the CRD of the Saccharomyces cerevisiae ATRIP ortholog Ddc2 disrupt the Ddc2-RPA interaction, prevent proper localization of Ddc2 to DNA breaks, sensitize yeast to DNA damaging agents, and partially compromise checkpoint signaling. These data demonstrate that the CRD is critical for localization and optimal DNA damage responses. However, the stimulation of ATR kinase activity by binding of topoisomerase binding protein 1 (TopBP1) to ATRIP-ATR can occur independently of the interaction of ATRIP with RPA. Our results support the idea of a multistep model for ATR activation that requires separable localization and activation functions of ATRIP. PMID- 17339345 TI - An in vitro model system used to study adherence and invasion of Francisella tularensis live vaccine strain in nonphagocytic cells. AB - In observing Francisella tularensis interactions with nonphagocytic cell lines in vitro, we noted significant adherence, invasion, and intracellular growth of the bacteria within these cells. F. tularensis live vaccine strain invasion of nonprofessional phagocytic cells is inhibited by cytochalasin D and nocodazole, suggesting that both the actin and microtubule cytoskeletons are important for invasion. PMID- 17339346 TI - Toxoplasma gondii strains defective in oral transmission are also defective in developmental stage differentiation. AB - Toxoplasma gondii undergoes differentiation from rapidly growing tachyzoites to slowly growing bradyzoites during its life cycle in the intermediate host, and conversion can be induced in vitro by stress. Representative strains of the three clonal lineages showed equal capacity to differentiate into bradyzoites in vitro, as evidenced by induction of bradyzoite antigen 1, staining with Dolichos biflorus lectin (DBL), pepsin resistance, and oral infectivity in mice. We also examined several recently described exotic strains of T. gondii, which are genetically diverse and have a different ancestry from the clonal lineages. The exotic strain COUG was essentially like the clonal lineages and showed a high capacity to induce bradyzoites in vitro and in vivo, consistent with its ability to be efficiently transmitted by the oral route. In contrast, exotic strains MAS and FOU, which are defective in oral transmission, showed a decreased potential to develop into bradyzoites in vitro. This defect was evident from reduced staining with DBL and the cyst antigen CST1, failure to down-regulate tachyzoite antigens, such as tachyzoite surface antigens 1 and 2A, and decreased resistance to pepsin treatment. Despite normal in vitro differentiation, the exotic strains CAST and GPHT also showed decreased oral transmission, due to formation of smaller cysts and a lower tissue burden during chronic infection, traits also shared by MAS and FOU. Collectively, these findings reveal that the limited oral transmission in some strains of T. gondii is due to inefficient differentiation to the bradyzoite form, leading to defects in the formation of tissue cysts. PMID- 17339347 TI - Immunogenicity of Anaplasma marginale type IV secretion system proteins in a protective outer membrane vaccine. AB - Rickettsial pathogens in the genera Anaplasma and Ehrlichia cause acute infection in immunologically naive hosts and are major causes of tick-borne disease in animals and humans. Immunization with purified outer membranes induces protection against acute Anaplasma marginale infection and disease, and a proteomic and genomic approach recently identified 21 proteins within the outer membrane immunogen in addition to the well-characterized major surface proteins MSP1 to MSP5. Among the newly described proteins were the type IV secretion system (TFSS) proteins VirB9, VirB10, and conjugal transfer protein (CTP). In other gram negative bacteria, TFSS proteins form channels, facilitate secretion of molecules, and are required for intracellular survival. However, TFSS proteins have not been explored as vaccine antigens. In this study we demonstrate that in Anaplasma marginale outer membrane-vaccinated cattle, VirB9, VirB10, and CTP are recognized by serum immunoglobulin G2 (IgG2) and stimulate memory T-lymphocyte proliferation and gamma interferon secretion. VirB9 induced the greatest proliferation in CD4+ T-cell lines, and VirB9-specific CD4+ T-cell clones responded to three A. marginale strains, confirming the VirB9-specific T-cell responses are directed against epitopes in the native protein. The three TFSS proteins are highly conserved with orthologous proteins in Anaplasma phagocytophilum, Ehrlichia chaffeensis, and Ehrlichia canis. Recognition of TFSS antigens by CD4+ T cells and by IgG2 from cattle immunized with the protective outer membrane fraction provides a rationale for including these proteins in development of vaccines against A. marginale and related pathogens. PMID- 17339348 TI - Anthrax edema toxin sensitizes DBA/2J mice to lethal toxin. AB - Anthrax toxin is made up of three separate protein components: the receptor binding protective antigen (PA), the adenylyl cyclase edema factor (EF), and the metalloproteinase lethal factor (LF). EF and PA constitute edema toxin (ET), which causes edema when injected subcutaneously. At higher doses, ET causes severe pathologies and death in BALB/cJ mice (A. M. Firoved et al., Am. J. Pathol. 167:1309-1320, 2005). A striking effect of ET at lethal doses is adrenal necrosis. Here we show that low doses of ET (10 microg) that produce no overt signs of illness in mice still cause substantial adrenal lesions. These lesions are not associated with reduced corticosterone production; instead, ET-treated mice have increased corticosterone production. Because the resistance of mice to the other component of anthrax toxin, lethal toxin (LT; LF plus PA), has been shown to be overcome by the perturbation of the endocrine system, we hypothesized that sublethal doses of ET might sensitize LT-resistant DBA/2J mice to LT mediated lethality. We report that a low dose of ET (5 microg) is sufficient to sensitize DBA/2J mice when given concurrently with LT. Higher doses of ET (e.g., 15 microg) given to male and female DBA/2J mice 18 h prior to LT challenge also sensitize them to LT. This study using highly purified ET and LT demonstrates how the components of anthrax toxin can work together to increase lethality. PMID- 17339349 TI - Flow cytometric analysis of adherence of Porphyromonas gingivalis to oral epithelial cells. AB - By using fluorescence microscopy, fluorescently labeled Porphyromonas gingivalis W50 was shown to adhere to oral epithelial (KB) cells as discrete cells or small cell aggregates, whereas P. gingivalis ATCC 33277 bound as large cell aggregates. Flow cytometric analysis showed that for P. gingivalis W50 there was a logarithmic relationship between the bacterial cell ratio (BCR), that is the number of bacterial cells to KB cells, and the percentage of KB cells with W50 cells attached. This percentage of KB cells with W50 attached reached a plateau of approximately 84% cells at a BCR of 500:1. In contrast, a quadratic relationship was observed between BCR and the percentage of KB cells with P. gingivalis ATCC 33277 attached, reaching a maximum of 47% at a BCR of 100:1 but decreasing to 7% at a BCR of 1,000:1. The lower binding of ATCC 33277 at high cell concentrations was attributed to autoaggregation. P. gingivalis W50 cells treated with an inhibitor (Nalpha-p-tosyl-L-lysine chloromethyl ketone [TLCK]) of its RgpA-Kgp proteinase-adhesin complex exhibited significantly reduced binding to KB cells than to untreated cells, suggesting a role for proteinase activity in binding to KB cells. Competitive inhibition with purified proteinase-active and TLCK-inactivated RgpA-Kgp complex significantly decreased the adherence of P. gingivalis W50 cells to KB cells. Furthermore, isogenic mutants of P. gingivalis W50 lacking the kgp gene product, but not the rgpA or rgpB gene products, exhibited significantly decreased adherence to KB cells compared to the wild type. PMID- 17339350 TI - Requirements for assembly of PtlH with the pertussis toxin transporter apparatus of Bordetella pertussis. AB - PtlH is an essential component of the Ptl system, the type IV transporter responsible for secretion of pertussis toxin (PT) across the outer membrane of Bordetella pertussis. The nine Ptl proteins are believed to interact to form a membrane-spanning apparatus through which the toxin is secreted. In this study, we monitored the subcellular localization of PtlH in strains of B. pertussis lacking PT, lacking other Ptl proteins, or from which ATP has been depleted in order to gain insight into the requirements for assembly of PtlH with the remainder of the Ptl transporter complex that is thought to be tightly embedded in the membrane. We found that PtlH is exclusively localized to the inner membrane fraction of the cell in a wild-type strain of B. pertussis. In contrast, PtlH localized to both the cytoplasmic and inner membrane fractions of a mutant strain of B. pertussis that does not produce PT. In comparison to how it localized in wild-type strains of B. pertussis, PtlH exhibited aberrant localization in strains lacking PtlD, PtlE, PtlF, and PtlG. We also found that localization of PtlH was perturbed in B. pertussis strains that were treated with carbonyl cyanide m-chlorophenylhydrazone and sodium arsenate, which are capable of depleting cellular ATP levels, and in strains of B. pertussis that produce an altered form of PtlH that lacks ATPase activity. When taken together, these results indicate that tight association of PtlH with the membrane, likely through interactions with components of the transporter-PT complex, requires the toxin substrate, a specific subset of the Ptl proteins, and ATP. Based on these data, a model for the assembly of the Ptl transporter-PT complex is presented. PMID- 17339351 TI - Interaction of Candida albicans with adherent human peripheral blood mononuclear cells increases C. albicans biofilm formation and results in differential expression of pro- and anti-inflammatory cytokines. AB - Monocytes and macrophages are the cell types most commonly associated with the innate immune response against Candida albicans infection. Interactions between the host immune system and Candida organisms have been investigated for planktonic Candida cells, but no studies have addressed these interactions in a biofilm environment. In this study, for the first time, we evaluated the ability of C. albicans to form biofilms in the presence or absence of adherent peripheral blood mononuclear cells (PBMCs; enriched for monocytes and macrophages by adherence). Our analyses using scanning electron and confocal scanning laser microscopy showed that the presence of PBMCs enhanced the ability of C. albicans to form biofilms and that the majority of PBMCs were localized to the basal and middle layers of the biofilm. In contrast to the interactions of PBMCs with planktonic C. albicans, where PBMCs phagocytose fungal cells, PBMCs did not appear to phagocytose fungal cells in biofilms. Furthermore, time-lapse laser microscopy revealed dynamic interactions between C. albicans and PBMCs in a biofilm. Additionally, we found that (i) only viable PBMCs influence Candida biofilm formation, (ii) cell surface components of PBMCs did not contribute to the enhancement of C. albicans biofilm, (iii) the biofilm-enhancing effect of PBMCs is mediated by a soluble factor released into the coculture medium of PBMCs with C. albicans, and (iv) supernatant collected from this coculture contained differential levels of pro- and anti-inflammatory cytokines. Our studies provide new insight into the interaction between Candida biofilm and host immune cells and demonstrate that immunocytes may influence the ability of C. albicans to form biofilms. PMID- 17339352 TI - Niche-specific activation of the oxidative stress response by the pathogenic fungus Candida albicans. AB - Candida albicans is a major opportunistic pathogen of humans. The pathogenicity of this fungus depends upon its ability to deal effectively with the host defenses and, in particular, the oxidative burst of phagocytic cells. We have explored the activation of the oxidative stress response in C. albicans in ex vivo infection models and during systemic infection of a mammalian host. We have generated C. albicans strains that contain specific green fluorescent protein (GFP) promoter fusions and hence act as biosensors of environmental oxidative stress at the single-cell level. Having confirmed that CTA1-, TRX1-, and TTR1/GRX2-GFP reporters respond specifically to oxidative stress, and not to heat shock, nitrosative, or osmotic stresses, we used these reporters to show that individual C. albicans cells activate an oxidative stress response following phagocytosis by neutrophils, but not by macrophages. Significantly, only a small proportion of C. albicans cells (about 4%) activated an oxidative stress response during systemic infection of the mouse kidney. The response of these cells was generally equivalent to exposure to 0.4 mM hydrogen peroxide in vitro. We conclude that most C. albicans cells are exposed to an oxidative stress when they come into contact with neutrophils in the bloodstream of the host but that oxidative killing is no longer a significant threat once an infection has been established in the kidney. PMID- 17339353 TI - CpG oligodeoxynucleotide treatment enhances innate resistance and acquired immunity to African trypanosomes. AB - Relative resistance to African trypanosomiasis is based on the development of a type I cytokine response, which is partially dependent on innate immune responses generated through MyD88 and Toll-like receptor 9 (TLR9). Therefore, we asked whether enhancement of the immune response by artificial stimulation with CpG oligodeoxynucleotide (ODN), a TLR9 agonist, would result in enhanced protection against trypanosomes. In susceptible BALB/c mice, relative resistance to infection was significantly enhanced by CpG ODN treatment and was associated with decreased parasite burden, increased cytokine production, and elevated parasite specific B- and T-cell responses. In relatively resistant C57BL/6 mice, survival was not enhanced but early parasitemia levels were reduced 100-fold and the majority of the parasites were nondividing, short stumpy (SS) forms. CpG ODN treatment of lymphocyte-deficient C57BL/6-scid and BALB/cByJ-scid mice also enhanced survival and reduced parasitemia, indicating that innate resistance to trypanosome infection can be enhanced. In C57BL/6-scid and BALB/cByJ-scid mice, the parasites were also predominantly SS forms during the outgrowth of parasitemia. However, the effect of CpG ODN treatment on parasite morphology was not as marked in gamma interferon (IFN-gamma)-knockout mice, suggesting that downstream effects of IFN-gamma production may play a discrete role in parasite cell differentiation. Overall, these studies provide the first evidence that enhancement of resistance to African trypanosomes can be induced in susceptible animals in a TLR9-dependent manner and that CpG ODN treatment may influence the developmental life cycle of the parasites. PMID- 17339354 TI - Shigella flexneri inhibits staurosporine-induced apoptosis in epithelial cells. AB - Shigella flexneri is a facultative intracellular organism that causes bacillary dysentery. The Shigella IpaB protein activates caspase 1 in macrophages, which eventually leads to apoptosis. In contrast, epithelial cells infected with Shigella undergo a stress response but do not die. Therefore, the objective of this study was to determine if Shigella has the ability to inhibit apoptosis in epithelial cells. A modified gentamicin protection assay was used to investigate if HeLa cells infected with S. flexneri are able to resist the induction of apoptosis following treatment with 4 microM of staurosporine. Nuclear staining and immunofluorescence revealed that infected cells remained healthy while uninfected cells appeared apoptotic. Only uninfected cells had detectable levels of activated caspase 3 upon immunofluorescence, and this was verified by Western blot analysis. Despite interfering with caspase 3 activation, Shigella-infected cells treated with staurosporine did have cytochrome c release and caspase 9 activation, indicating that Shigella protects epithelial cells from apoptosis by inhibiting caspase 3 activation. Analysis of S. flexneri mutants showed that invasion and a functional type III secretion system were required to block apoptosis. In addition, a mutant with a deletion in mxiE, which encodes a transcriptional activator for genes induced intracellularly, failed to inhibit apoptosis. Therefore, protection of epithelial cells from apoptosis by S. flexneri is regulated by one or more of the bacterial genes under the control of mxiE. We believe that S. flexneri, like other pathogens, inhibits apoptosis in epithelial cells but causes apoptosis in macrophages to ensure survival inside the host. PMID- 17339355 TI - Role of Bacillus anthracis spore structures in macrophage cytokine responses. AB - The innate immune response of macrophages (Mphi) to spores, the environmentally acquired form of Bacillus anthracis, is poorly characterized. We therefore examined the early Mphi cytokine response to B. anthracis spores, before germination. Mphi were exposed to bacilli and spores of Sterne strain 34F2 and its congenic nongerminating mutant (DeltagerH), and cytokine expression was measured by real-time PCR and an enzyme-linked immunosorbent assay. The exosporium spore layer was retained (exo+) or removed by sonication (exo-). Spores consistently induced a strong cytokine response, with the exo- spores eliciting a two- to threefold-higher response than exo+ spores. The threshold for interleukin-1beta (IL-1beta) production by wild-type Mphi was significantly lower than that required for tumor necrosis factor alpha expression. Cytokine production was largely dependent on MyD88, suggesting Toll-like receptor involvement; however, the expression of beta interferon in MyD88-/- Mphi suggests involvement of a MyD88-independent pathway. We conclude that (i) the B. anthracis spore is not immunologically inert, (ii) the exosporium masks epitopes recognized by the Mphi, (iii) the Mphi cytokine response to B. anthracis involves multiple pattern recognition receptors and signaling pathways, and (iv) compared to other cytokines, IL-1beta is expressed at a lower spore concentration. PMID- 17339356 TI - Uninfected mosquito bites confer protection against infection with malaria parasites. AB - Despite decades of research and multiple initiatives, malaria continues to be one of the world's most debilitating infectious diseases. New insights for malaria control and vaccine development will be essential to thwart the staggering worldwide impact of this disease (A. Bjorkman and A. Bhattarai, Acta Trop. 94:163 169, 2005); ultimately successful vaccine strategies will undoubtedly be multifactorial, incorporating multiple antigens and targeting diverse aspects of the malaria parasites' biology (M. F. Good et al., Immunol. Rev. 201:254-267, 2004). Using a murine model of malaria infection, we show here that exposure to bites from uninfected mosquitoes prior to Plasmodium yoelii infection influences the local and systemic immune responses and limits parasite development within the host. In hosts preexposed to bites from uninfected mosquitoes, reduced parasite burdens in the livers were detected early, and during the blood-stage of the life cycle, these burdens remained lower than those in hosts that received mosquito bites only at the time of infection. Repeated exposure to bites from uninfected mosquitoes skewed the immune response towards a T-helper 1 (Th1) phenotype as indicated by increased levels of interleukin-12, gamma interferon, and inducible nitric oxide synthase. These data suggest that the addition of mosquito salivary components to antimalaria vaccines may be a viable strategy for creating a Th1-biased environment known to be effective against malaria infection. Furthermore, this strategy may be important for the development of vaccines to combat other mosquito-transmitted pathogens. PMID- 17339357 TI - Immunomodulatory effects of the Lutzomyia longipalpis salivary gland protein maxadilan on mouse macrophages. AB - Infection with Leishmania major is enhanced when the sand fly Lutzomyia longipalpis salivary peptide maxadilan (MAX) is injected along with the parasite. Here we determined the effect that MAX has on the secretion of cytokines and nitric oxide (NO) and on parasite survival in macrophages (MPhis). The cytokines produced by MPhis can enhance a type 1 response, which will increase NO and the killing of intracellular pathogens such as L. major, or a type 2 response, leading to antibody production that is ineffective against intracellular pathogens such as L. major. A mouse macrophage cell line (RAW 264.7) was stimulated with various concentrations of MAX and lipopolysaccharide (LPS), and the supernatants were collected after 1, 2, and 3 days. Supernatants were assayed for interleukin-12p70 (IL-12p70), IL-10, IL-6, transforming growth factor beta (TGF-beta), NO, and tumor necrosis factor alpha (TNF-alpha). Our results indicate that the addition of MAX upregulates the cytokines associated with a type 2 response (IL-10, IL-6, and TGF-beta) but downregulates type 1 cytokines (IL-12p70 and TNF-alpha) and NO. MAX was also added to L. major-infected mouse peritoneal exudate cells (PECs), and the parasite load increased significantly. The enhanced parasite load correlated with decreased NO production by PECs that were stimulated with LPS and gamma interferon in the presence of MAX. The ability of MAX to foster a type 2 response, to enhance parasite survival, and to decrease NO argues that MAX may be crucial for the early survival of Leishmania in the vertebrate host, and therefore, MAX holds considerable promise as an antigenic component for a vaccine against Leishmania. PMID- 17339358 TI - Modulation of gamma interferon receptor 1 by Mycobacterium tuberculosis: a potential immune response evasive mechanism. AB - Mycobacterium tuberculosis inhibits gamma interferon (IFN-gamma)-mediated antimycobacterial action by adopting diverse mechanisms. IFN-gamma binds to its receptor, IFN-gammaR, in order to initiate proper signaling. We have observed reduced surface expression levels of IFN-gamma receptor 1 (IFN-gammaR1) in untreated pulmonary tuberculosis patients compared to those in healthy individuals (P < 0.01). Following antitubercular therapy, the expression of IFN gammaR1 was restored in these patients. To delineate the mechanism by which M. tuberculosis modulates IFN-gammaR1, in vitro experiments were designed, wherein the down modulation of IFN-gammaR1 surface expression was observed for CD14+ cells in peripheral blood mononuclear cells (PBMCs) cocultured with live M. tuberculosis compared to that for uninfected cells (P < 0.01). No modulation of IFN-gammaR1 expression was observed for CD14+ cells in PBMCs infected with Mycobacterium smegmatis. A time-dependent decrease in IFN-gammaR1 mRNA expression was observed for PBMCs infected with M. tuberculosis. Similar down modulation of IFN-gammaR1 protein and mRNA expression in phorbol myristate acetate differentiated THP-1 cells (pdTHP-1) by M. tuberculosis was observed (P < 0.01). Using reporter gene analysis of 5' deletion constructs of the IFN-gammaR1 gene (IFNGR1) promoter, the decrease in IFN-gammaR1 mRNA in M. tuberculosis-infected pdTHP-1 cells was shown to be due to the decreased transcription of IFNGR1. By immunoblotting and electrophoretic mobility shift assays, the down regulation of stimulating protein 1 (Sp1) expression and its recruitment on the phorbol ester responsive element of the IFNGR1 promoter in M. tuberculosis-infected pdTHP-1 cells was observed. This down regulation of Sp1 in pdTHP-1 cells cocultured with M. tuberculosis may be responsible for the down regulation of IFN-gammaR1 expression, thereby potentially altering its receptivity to IFN-gamma. PMID- 17339359 TI - Live attenuated Streptococcus pneumoniae strains induce serotype-independent mucosal and systemic protection in mice. AB - Streptococcus pneumoniae is an important human pathogen causing both mucosal (otitis media and pneumonia) and systemic (sepsis and meningitis) diseases. Due to increasing rates of antibiotic resistance, there is an urgent need to improve prevention of pneumococcal disease. Two currently licensed vaccines have been successful in reducing pneumococcal disease, but there are limitations with their use and effectiveness. Another approach for prevention is the use of live attenuated vaccines. Here we investigate the safety and protection induced by live attenuated strains of S. pneumoniae containing combinations of deletions in genes encoding three of its major virulence determinants: capsular polysaccharide (cps), pneumolysin (ply), and pneumococcal surface protein A (pspA). Both the cps and ply/pspA mutants of a virulent type 6A isolate were significantly attenuated in a mouse model of sepsis. These attenuated strains retained the ability to colonize the upper respiratory tract. A single intranasal administration of live attenuated vaccine without adjuvant was sufficient to induce both systemic and mucosal protection from challenge with a high dose of the parent strain. Immunization with cps mutants demonstrated cross-protective immunity following challenge with a distantly related isolate. Serum and mucosal antibody titers were significantly increased in mice immunized with the vaccine strains, and this antibody is required for full protection, as microMT mice, which do not make functional, specific antibody, were not protected by immunization with vaccine strains. Thus, colonization by live attenuated S. pneumoniae is a potentially safe and less complex vaccine strategy that may offer broad protection. PMID- 17339360 TI - Enteropathogenic Escherichia coli-induced epidermal growth factor receptor activation contributes to physiological alterations in intestinal epithelial cells. AB - The diarrheagenic pathogen enteropathogenic Escherichia coli (EPEC) is responsible for significant infant mortality and morbidity, particularly in developing countries. EPEC pathogenesis relies on a type III secretion system mediated transfer of virulence effectors into host cells. EPEC modulates host cell survival and inflammation, although the proximal signaling pathways have not been well defined. We therefore examined the effect of EPEC on the epidermal growth factor receptor (EGFR), a known upstream activator of both the prosurvival phosphoinositide 3-kinase/Akt and proinflammatory mitogen-activated protein (MAP) kinase pathways. EPEC induced the autophosphorylation of EGFR in intestinal epithelial cells within 15 min postinfection, with maximal phosphorylation being observed at 4 h. Filter-sterilized supernatants of EPEC cultures also stimulated EGFR phosphorylation, suggesting that a secreted component(s) contributes to this activity. EPEC-induced EGFR phosphorylation was blocked by the pharmacological inhibitor tyrphostin AG1478, as well as by EGFR-neutralizing antibodies. Inhibition of EGFR phosphorylation by AG1478 had no effect on bacterial adherence, actin recruitment to sites of attachment, or EPEC-induced epithelial barrier function alteration. EPEC-mediated Akt phosphorylation, however, was inhibited by both AG1478 and EGFR-neutralizing antibodies. Correspondingly, inhibition of EGFR activation increased the apoptosis/necrosis of infected epithelial cells. Inhibition of EGFR phosphorylation also curtailed EPEC-induced ERK1/2 (MAP kinase) phosphorylation and, correspondingly, the production of the proinflammatory cytokine interleukin-8 by infected epithelial cells. Our studies suggest that EGFR is a key proximal signaling molecule during EPEC pathogenesis. PMID- 17339361 TI - QseA directly activates transcription of LEE1 in enterohemorrhagic Escherichia coli. AB - Quorum sensing (QS) in enterohemorrhagic Escherichia coli (EHEC) regulates the expression of the locus of enterocyte effacement (LEE). The LEE contains five major operons named LEE1 through LEE5. QseA was previously shown to be activated through QS and to activate the transcription of LEE1. The LEE1 operon encodes Ler, the transcription activator of all other LEE genes, and has two promoters: a distal promoter (P1) and a proximal promoter (P2). We have previously reported that QseA acts on P1 and not P2. To identify the minimal region of LEE1 that is necessary for QseA-mediated activation, a series of nested-deletion constructs of the LEE1 promoter fused to a lacZ reporter were constructed in both the EHEC and E. coli K-12 backgrounds. In an EHEC background, QseA-dependent activation of LEE1 can be observed for the entire regulatory region (beginning at nucleotide 393 and ending at nucleotide -123). In contrast to what occurred in EHEC, in K-12 there was no QseA-dependent activation of LEE1 transcription between base pairs 393 and -343. These data indicate that a QseA-dependent EHEC-specific regulator is required for the activation of transcription in this region. We also observed QseA-dependent LEE1 activation from nucleotides -218 to -123 in K-12, similar to results of the nested-deletion analysis performed with EHEC. Electrophoretic mobility shift assays established that QseA directly binds to the region of LEE1 from bp -173 to -42 and not to the region from bp -393 to -343. These studies suggest that QseA activates the transcription of LEE1 by directly binding upstream of its P1 promoter region. PMID- 17339362 TI - Virulence plasmid diversity in Clostridium perfringens type D isolates. AB - Clostridium perfringens type D isolates are important in biodefense and also cause natural enterotoxemias in sheep, goats, and occasionally cattle. In these isolates, the gene (etx) encoding epsilon-toxin is thought to reside on poorly characterized large plasmids. Type D isolates sometimes also produce other potentially plasmid-encoded toxins, including C. perfringens enterotoxin and beta2 toxin, encoded by the cpe and cbp2 genes, respectively. In the current study we demonstrated that the etx, cpe, and cpb2 genes are carried on plasmids in type D isolates and characterized the toxin-encoding plasmids to obtain insight into their genetic organization, potential transferability, and diversity. Southern blotting of pulsed-field gels showed that the etx gene of type D isolates can be present on at least five different plasmids, whose sizes range from 48 to 110 kb. The etx plasmids also typically carried IS1151 and tcp open reading frames (ORFs) known to mediate conjugative transfer of C. perfringens plasmid pCW3. PCR studies revealed that other than their tcp ORFs, etx plasmids of type D isolates do not carry substantial portions of the conserved or variable regions in the cpe plasmids of type A isolates. Southern blotting also demonstrated that in type D isolates the cpe and cpb2 genes are sometimes present on the etx plasmid. Collectively, these findings confirmed that the virulence of type D isolates is heavily plasmid dependent and indicated that (i) a single type D isolate can carry multiple virulence plasmids, (ii) a single type D virulence plasmid can carry up to three different toxin genes, and (iii) many etx plasmids should be capable of conjugative transfer. PMID- 17339364 TI - Transcript and protein expression profiles of the NCI-60 cancer cell panel: an integromic microarray study. AB - To evaluate the utility of transcript profiling for prediction of protein expression levels, we compared profiles across the NCI-60 cancer cell panel, which represents nine tissues of origin. For that analysis, we present here two new NCI-60 transcript profile data sets (A based on Affymetrix HG-U95 and HG U133A chips; Affymetrix, Santa Clara, CA) and one new protein profile data set (based on reverse-phase protein lysate arrays). The data sets are available online at http://discover.nci.nih.gov in the CellMiner program package. Using the new transcript data in combination with our previously published cDNA array and Affymetrix HU6800 data sets, we first developed a "consensus set" of transcript profiles based on the four different microarray platforms. Using that set, we found that 65% of the genes showed statistically significant transcript-protein correlation, and the correlations were generally higher than those reported previously for panels of mammalian cells. Using the predictive analysis of microarray nearest shrunken centroid algorithm for functional prediction of tissue of origin, we then found that (a) the consensus mRNA set did better than did data from any of the individual mRNA platforms and (b) the protein data seemed to do somewhat better (P = 0.027) on a gene-for-gene basis in this particular study than did the consensus mRNA data, but both did well. Analysis based on the Gene Ontology showed protein levels of structure-related genes to be well predicted by mRNA levels (mean r = 0.71). Because the transcript-based technologies are more mature and are currently able to assess larger numbers of genes at one time, they continue to be useful, even when the ultimate aim is information about proteins. PMID- 17339363 TI - Mucosal tissue invasion by Candida albicans is associated with E-cadherin degradation, mediated by transcription factor Rim101p and protease Sap5p. AB - The ability of Candida albicans to invade mucosal tissues is a major virulence determinant of this organism; however, the mechanism of invasion is not understood in detail. Proteolytic breakdown of E-cadherin, the major protein in epithelial cell junctions, has been proposed as a mechanism of invasion of certain bacteria in the oral mucosa. The objectives of this study were (i) to assess whether C. albicans degrades E-cadherin expressed by oral epithelial cells in vitro; (ii) to compare the abilities of strains with different invasive potentials to degrade this protein; and (iii) to investigate fungal virulence factors responsible for E-cadherin degradation. We found that while E-cadherin gene expression was not altered, E-cadherin was proteolytically degraded during the interaction of oral epithelial cells with C. albicans. Moreover, C. albicans mediated degradation of E-cadherin was completely inhibited in the presence of protease inhibitors. Using a three-dimensional model of the human oral mucosa, we found that E-cadherin was degraded in localized areas of tissue invasion by C. albicans. An invasion-deficient rim101-/rim101- strain was deficient in degradation of E-cadherin, and this finding suggested that proteases may depend on Rim101p for expression. Indeed, reverse transcription-PCR data indicated that expression of the SAP4, SAP5, and SAP6 genes is severely reduced in the rim101 /rim101- mutant. These SAP genes are functional Rim101p targets, because engineered expression of SAP5 in the rim101-/rim101- strain restored E-cadherin degradation and invasion in the mucosal model. Our data support the hypothesis that there is a mechanism by which C. albicans invades mucosal tissues by promoting the proteolytic degradation of E-cadherin in epithelial adherens junctions. PMID- 17339365 TI - Selenium sensitizes MCF-7 breast cancer cells to doxorubicin-induced apoptosis through modulation of phospho-Akt and its downstream substrates. AB - Doxorubicin is an effective drug against breast cancer. However, the favorable therapeutic response to doxorubicin is often associated with severe toxicity. The present research was aimed at developing a strategy of increasing doxorubicin sensitivity so that lower doses may be used without compromising efficacy. The MCF-7 human breast cancer cell line currently in use in our laboratory did not respond to doxorubicin cell killing during a 24-h treatment period. By combining doxorubicin with selenium, we were successful in producing a brisk enhancement of apoptosis. We examined the effects of these two agents on Akt activation and found that selenium was capable of depressing doxorubicin-induced Akt phosphorylation. Several lines of evidence converged to support the notion that this effect is important in mediating the synergy between selenium and doxorubicin. Selenium was no longer able to sensitize cells to doxorubicin under a condition in which Akt was constitutively activated. Increased Akt phosphorylation following treatment with doxorubicin was accompanied by increased phosphorylation of glycogen synthase kinase 3beta (GSK3beta) and FOXO3A, which are substrates of Akt (both GSK3beta and FOXO3A lose their proapoptotic activities when they are phosphorylated). Selenium reduced the abundance of phospho-GSK3beta induced by doxorubicin, whereas chemical inhibition of GSK3beta activity muted the apoptotic response to the selenium/doxorubicin combination. Additional experiments showed that selenium increased the transactivation activity of FOXO3A, as evidenced by a reporter gene assay, as well as by the elevated expression of Bim (a target gene of FOXO3A). The functional significance of Bim was confirmed by the observation that RNA interference of Bim markedly reduced the potency of selenium/doxorubicin to induce apoptosis. PMID- 17339367 TI - Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. AB - Sulforaphane, an isothiocyanate found in cruciferous vegetables, has been shown to induce phase 2 detoxication enzymes and inhibit the growth of chemically induced mammary tumors in rats, although the exact mechanisms of action of sulforaphane are not understood. In this study, we evaluated the effects of sulforaphane on cell growth and death in several human breast cancer cell lines and examined the hypothesis that sulforaphane acts as a histone deacetylase (HDAC) inhibitor in these cell lines. Sulforaphane treatment inhibited cell growth, induced a G(2)-M cell cycle block, increased expression of cyclin B1, and induced oligonucleosomal DNA fragmentation in the four human breast cancer cell lines examined, MDA-MB-231, MDA-MB-468, MCF-7, and T47D cells. Activation of apoptosis by sulforaphane in MDA-MB-231 cells seemed to be initiated through induction of Fas ligand, which resulted in activation of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, whereas apoptosis in the other breast cancer cell lines was initiated by decreased Bcl-2 expression, release of cytochrome c into the cytosol, activation of caspase-9 and caspase-3, but not caspase-8, and poly(ADP-ribose) polymerase cleavage. Sulforaphane inhibited HDAC activity and decreased the expression of estrogen receptor-alpha, epidermal growth factor receptor, and human epidermal growth factor receptor-2 in each cell line, although no change in the acetylation of H3 or H4 was seen. These data suggest that sulforaphane inhibits cell growth, activates apoptosis, inhibits HDAC activity, and decreases the expression of key proteins involved in breast cancer proliferation in human breast cancer cells. These results support testing sulforaphane in vivo and warrant future studies examining the clinical potential of sulforaphane in human breast cancer. PMID- 17339366 TI - Targeting the apoptotic machinery in pancreatic cancers using small-molecule antagonists of the X-linked inhibitor of apoptosis protein. AB - Resistance to apoptosis is a hallmark of many solid tumors, including pancreatic cancers, and may be the underlying basis for the suboptimal response to chemoradiation therapies. Overexpression of a family of inhibitor of apoptosis proteins (IAP) is commonly observed in pancreatic malignancies. We determined the therapeutic efficacy of recently described small-molecule antagonists of the X linked IAP (XIAP) in preclinical models of pancreatic cancer. Primary pancreatic cancers were assessed for XIAP expression by immunohistochemistry, using a pancreatic cancer tissue microarray. XIAP small-molecule antagonists ("XAntag"; compounds 1396-11 and 1396-12) and the related compound 1396-28 were tested in vitro in a panel of human pancreatic cancer cell lines (Panc1, Capan1, and BxPC3) and in vivo in s.c. xenograft models for their ability to induce apoptosis and impede neoplastic growth. In addition, pancreatic cancer cell lines were treated with XAntags in conjunction with either tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or with radiation to determine potential synergy for such dual targeting of the apoptotic machinery. XIAP was overexpressed in 14 of 18 (77%) of primary pancreatic cancers. The XAntags1396-11 and 1396-12, but not the inactive isomer 1396-28, induced profound apoptosis in multiple pancreatic cancer cell lines tested in vitro, with a IC(50) in the range of 2 to 5 mumol/L. Mechanistic specificity of the XAntags for the baculoviral IAP repeat-2 domain of XIAP was shown by preferential activation of downstream "effector" caspases (caspase-3 and caspase-7) versus the upstream "initiator" caspase-9. S.c. BxPC3 xenograft growth in athymic mice was significantly inhibited by monotherapy with XAntags; treated xenografts showed marked apoptosis and increased cleavage of caspase-3. Notably, striking synergy was demonstrable when XAntags were combined with either TRAIL or radiation therapy, as measured by growth inhibition in vitro and reduced colony formation in soft agar of pancreatic cancer cell lines, at dosages where these therapeutic modalities had minimal to modest effects when used alone. Finally, XAntags in combination with the standard-of-care agent for advanced pancreatic cancer, gemcitabine, resulted in significantly greater inhibition of in vitro growth than gemcitabine alone. Our results confirm that pharmacologic inhibition of XIAP is a potent therapeutic modality in pancreatic cancers. These antagonists are independently capable of inducing pancreatic cancer cell death and also show synergy when combined with proapoptotic ligands (TRAIL), with radiation, and with a conventional antimetabolite, gemcitabine. These preclinical results suggest that targeting of the apoptotic machinery in pancreatic cancers with XAntags is a promising therapeutic option that warrants further evaluation. PMID- 17339368 TI - Modulation of cancer cell survival pathways using multivalent liposomal therapeutic antibody constructs. AB - Various methods have been explored to enhance antibody-based cancer therapy. The use of multivalent antibodies or fragments against tumor antigens has generated a great deal of interest, as various cellular signals, including induction of apoptosis, inhibition of cell growth/survival, or internalization of the surface molecules, can be triggered or enhanced on extensive cross-linking of the target/antibody complex by the multivalent form of the antibody. The goal of the studies reported here was to develop multivalent antibody constructs via grafting of antibody molecules onto liposome membranes to enhance antibody activity. Using trastuzumab and rituximab as examples, up to a 25-fold increase in the antibody potency in cell viability assay was observed when the antibodies were presented in the multivalent liposome formulation. Key cell survival signaling molecules, such as phosphorylated Akt and phosphorylated p65 nuclear factor-kappaB, were down-regulated on treatment with multivalent liposomal trastuzumab and liposomal rituximab, respectively. Potent in vivo antitumor activity was shown for liposomal trastuzumab. The data presented here showed the potential of liposome technology to enhance the therapeutic effect of antibodies via a mechanism that modulates cell survival through clustering of the target/antibody complex. PMID- 17339369 TI - The evolutionary history of human DNA transposons: evidence for intense activity in the primate lineage. AB - Class 2, or DNA transposons, make up approximately 3% of the human genome, yet the evolutionary history of these elements has been largely overlooked and remains poorly understood. Here we carried out the first comprehensive analysis of the activity of human DNA transposons over the course of primate evolution using three independent computational methods. First, we conducted an exhaustive search for human DNA transposons nested within L1 and Alu elements known to be primate specific. Second, we assessed the presence/absence of 794 human DNA transposons at orthologous positions in 10 mammalian species using sequence data generated by The ENCODE Project. These two approaches, which do not rely upon sequence divergence, allowed us to classify DNA transposons into three different categories: anthropoid specific (40-63 My), primate specific (64-80 My), and eutherian wide (81-150 My). Finally, we used this data to calculate the substitution rates of DNA transposons for each category and refine the age of each family based on the average percent divergence of individual copies to their consensus. Based on these combined methods, we can confidently estimate that at least 40 human DNA transposon families, representing approximately 98,000 elements ( approximately 33 Mb) in the human genome, have been active in the primate lineage. There was a cessation in the transpositional activity of DNA transposons during the later phase of the primate radiation, with no evidence of elements younger than approximately 37 My. This data points to intense activity of DNA transposons during the mammalian radiation and early primate evolution, followed, apparently, by their mass extinction in an anthropoid primate ancestor. PMID- 17339370 TI - Evaluation of predicted network modules in yeast metabolism using NMR-based metabolite profiling. AB - Genome-scale metabolic models promise important insights into cell function. However, the definition of pathways and functional network modules within these models, and in the biochemical literature in general, is often based on intuitive reasoning. Although mathematical methods have been proposed to identify modules, which are defined as groups of reactions with correlated fluxes, there is a need for experimental verification. We show here that multivariate statistical analysis of the NMR-derived intra- and extracellular metabolite profiles of single-gene deletion mutants in specific metabolic pathways in the yeast Saccharomyces cerevisiae identified outliers whose profiles were markedly different from those of the other mutants in their respective pathways. Application of flux coupling analysis to a metabolic model of this yeast showed that the deleted gene in an outlying mutant encoded an enzyme that was not part of the same functional network module as the other enzymes in the pathway. We suggest that metabolomic methods such as this, which do not require any knowledge of how a gene deletion might perturb the metabolic network, provide an empirical method for validating and ultimately refining the predicted network structure. PMID- 17339371 TI - Inferring genome-wide functional linkages in E. coli by combining improved genome context methods: comparison with high-throughput experimental data. AB - Cellular functions are determined by interactions among proteins in the cells. Recognition of these interactions forms an important step in understanding biology at the systems level. Here, we report an interaction network of Escherichia coli, obtained by training a Support Vector Machine on the high quality of interactions in the EcoCyc database, and with the assumption that the periplasmic and cytoplasmic proteins may not interact with each other. The data features included correlation coefficient between bit score phylogenetic profiles, frequency of their co-occurrence in predicted operons, and a new measure--the distance between translational start sites of the genes. The combined genome context methods show a high accuracy of prediction on the test data and predict a total of 78,122 binary interactions. The majority of the interactions identified by high-throughput experimental methods correspond to indirect interaction (interactions through neighbors) in the predicted network. Correlation of the predicted network with the gene essentiality data shows that the essential genes in E. coli exhibit a high linking number, whereas the nonessential genes exhibit a low linking number. Furthermore, our predicted protein-protein interaction network shows that the proteins involved in replication, DNA repair, transcription, translation, and cell wall synthesis are highly connected. We therefore believe that our predicted network will serve as a useful resource in understanding prokaryotic biology. PMID- 17339373 TI - Immunomodulatory peptide from cystatin, a natural cysteine protease inhibitor, against leishmaniasis as a model macrophage disease. AB - Cystatin, a natural cysteine protease inhibitor, has strong antileishmanial activity, which is due to its potential to induce nitric oxide (NO) generation from macrophages. Cysteine protease-inhibitory activity and NO-up-regulatory activity correspond to different regions, as revealed by the dissection of cystatin cDNA into nonoverlapping fragments. By using synthetic overlapping peptides, the NO-up-regulatory activity was found to be confined to a 10-mer sequence. In addition to having reasonable inhibitory effects on amastigote multiplication within macrophages (50% inhibitory concentration, 5.2 microg/ml), 97 and 93% suppression, respectively, of liver and spleen parasite burdens was achieved with the 10-mer peptide at a dose of 0.5 mg/kg of body weight/day, given consecutively for 4 days along with a suboptimal dose of gamma interferon in a 45 day mouse model of visceral leishmaniasis. Peptide treatment modulated the levels of cytokine secretion by infected splenocytes, with increased levels of interleukin-12 and tumor necrosis factor alpha and increased inducible NO synthase production, and also resulted in resistance to reinfection. The generation of a natural peptide from cystatin with robust immunomodulatory potential may therefore provide a promising therapeutic agent for macrophage associated diseases. PMID- 17339372 TI - Evaluation of the metS and murB loci for antibiotic discovery using targeted antisense RNA expression analysis in Bacillus anthracis. AB - The biowarfare-relevant bacterial pathogen Bacillus anthracis contains two paralogs each of the metS and murB genes, which encode the important antibiotic target functions methionyl-tRNA synthetase and UDP-N acetylenolpyruvoylglucosamine reductase, respectively. Empirical screens were conducted to detect and characterize gene fragments of each of these four genes that could cause growth reduction of B. anthracis when inducibly expressed from a plasmid-borne promoter. Numerous such gene fragments that were overwhelmingly in the antisense orientation were identified for the metS1 and murB2 alleles, while no such orientation bias was seen for the metS2 and murB1 alleles. Gene replacement mutagenesis was used to confirm the essentiality of the metS1 and murB2 alleles, and the nonessentiality of the metS2 and murB1 alleles, for vegetative growth. Induced transcription of RNA from metS1 and murB2 antisense oriented gene fragments resulted in specific reduction of mRNA of their cognate genes. Attenuation of MetS1 enzyme expression hypersensitized B. anthracis cells to a MetS-specific antimicrobial compound but not to other antibiotics that affect cell wall assembly, fatty acid biosynthesis, protein translation, or DNA replication. Antisense-dependent reduction of MurB2 enzyme expression caused hypersensitivity to beta-lactam antibiotics, a synergistic response that has also been noted for the MurA-specific antibiotic fosfomycin. These experiments form the basis of mode-of-action detection assays that can be used in the discovery of novel MetS- or MurB-specific antibiotic drugs that are effective against B. anthracis or other gram-positive bacterial pathogens. PMID- 17339374 TI - Artemisinins inhibit Trypanosoma cruzi and Trypanosoma brucei rhodesiense in vitro growth. AB - Artemisinin compounds inhibit in vitro growth of cultured Trypanosoma cruzi and Trypanosoma brucei rhodesiense at concentrations in the low micromolar range. Artemisinin also inhibits calcium-dependent ATPase activity in T. cruzi membranes, suggesting a mode of action via membrane pumps. Artemisinins merit further investigation as chemotherapeutic options for these pathogens. PMID- 17339375 TI - Exo70p mediates the secretion of specific exocytic vesicles at early stages of the cell cycle for polarized cell growth. AB - In budding yeast, two classes of post-Golgi secretory vesicles carrying different sets of cargoes typified by Bgl2p and invertase are delivered to the plasma membrane for secretion. The exocyst is implicated in tethering these vesicles to the daughter cell membrane for exocytosis. In this study, we report that mutations in the exocyst component Exo70p predominantly block secretion of the Bgl2p vesicles. Furthermore, a defect in invertase vesicle trafficking caused by vps1Delta or pep12Delta in the exo70 mutant background is detrimental to the cell. The secretion defect in exo70 mutants was most pronounced during the early budding stage, which affected daughter cell growth. The selective secretion block does not occur at the vesicle formation or sorting stage because the exocytic vesicles are properly generated and protein processing is normal in the exo70 mutants. Our study suggests that Exo70p functions primarily at early stages of the cell cycle in Bgl2p vesicle secretion, which is critical for polarized cell growth. PMID- 17339376 TI - SYCE2 is required for synaptonemal complex assembly, double strand break repair, and homologous recombination. AB - Synapsis is the process by which paired chromosome homologues closely associate in meiosis before crossover. In the synaptonemal complex (SC), axial elements of each homologue connect through molecules of SYCP1 to the central element, which contains the proteins SYCE1 and -2. We have derived mice lacking SYCE2 protein, producing males and females in which meiotic chromosomes align and axes form but do not synapse. Sex chromosomes are unaligned, not forming a sex body. Additionally, markers of DNA breakage and repair are retained on the axes, and crossover is impaired, culminating in both males and females failing to produce gametes. We show that SC formation can initiate at sites of SYCE1/SYCP1 localization but that these points of initiation cannot be extended in the absence of SYCE2. SC assembly is thus dependent on SYCP1, SYCE1, and SYCE2. We provide a model to explain this based on protein-protein interactions. PMID- 17339377 TI - Xenopus tropicalis egg extracts provide insight into scaling of the mitotic spindle. AB - The African clawed frog Xenopus laevis has been instrumental to investigations of both development and cell biology, but the utility of this model organism for genetic and proteomic studies is limited by its long generation time and unsequenced pseudotetraploid genome. Xenopus tropicalis, which is a small, faster breeding relative of X. laevis, has recently been adopted for research in developmental genetics and functional genomics, and has been chosen for genome sequencing. We show that X. tropicalis egg extracts reconstitute the fundamental cell cycle events of nuclear formation and bipolar spindle assembly around exogenously added sperm nuclei. Interestingly, X. tropicalis spindles were approximately 30% shorter than X. laevis spindles, and mixing experiments revealed a dynamic, dose-dependent regulation of spindle size by cytoplasmic factors. Measurements of microtubule dynamics revealed that microtubules polymerized slower in X. tropicalis extracts compared to X. laevis, but that this difference is unlikely to account for differences in spindle size. Thus, in addition to expanding the range of developmental and cell biological experiments, the use of X. tropicalis provides novel insight into the complex mechanisms that govern spindle morphogenesis. PMID- 17339378 TI - Fork head controls the timing and tissue selectivity of steroid-induced developmental cell death. AB - Cell death during Drosophila melanogaster metamorphosis is controlled by the steroid hormone 20-hydroxyecdysone (20E). Elements of the signaling pathway that triggers death are known, but it is not known why some tissues, and not others, die in response to a particular hormone pulse. We found that loss of the tissue specific transcription factor Fork head (Fkh) is both required and sufficient to specify a death response to 20E in the larval salivary glands. Loss of fkh itself is a steroid-controlled event that is mediated by the 20E-induced BR-C gene, and that renders the key death regulators hid and reaper hormone responsive. These results implicate the D. melanogaster FOXA orthologue Fkh with a novel function as a competence factor for steroid-controlled cell death. They explain how a specific tissue is singled out for death, and why this tissue survives earlier hormone pulses. More generally, they suggest that cell identity factors like Fkh play a pivotal role in the normal control of developmental cell death. PMID- 17339379 TI - Functional genomics identifies a Myb domain-containing protein family required for assembly of CENP-A chromatin. AB - Nucleosomes containing the centromere-specific histone H3 variant centromere protein A (CENP-A) create the chromatin foundation for kinetochore assembly. To understand the mechanisms that selectively target CENP-A to centromeres, we took a functional genomics approach in the nematode Caenorhabditis elegans, in which failure to load CENP-A results in a signature kinetochore-null (KNL) phenotype. We identified a single protein, KNL-2, that is specifically required for CENP-A incorporation into chromatin. KNL-2 and CENP-A localize to centromeres throughout the cell cycle in an interdependent manner and coordinately direct chromosome condensation, kinetochore assembly, and chromosome segregation. The isolation of KNL-2-associated chromatin coenriched CENP-A, indicating their close proximity on DNA. KNL-2 defines a new conserved family of Myb DNA-binding domain-containing proteins. The human homologue of KNL-2 is also specifically required for CENP-A loading and kinetochore assembly but is only transiently present at centromeres after mitotic exit. These results implicate a new protein class in the assembly of centromeric chromatin and suggest that holocentric and monocentric chromosomes share a common mechanism for CENP-A loading. PMID- 17339380 TI - Propagation of centromeric chromatin requires exit from mitosis. AB - Centromeres direct chromosomal inheritance by nucleating assembly of the kinetochore, a large multiprotein complex required for microtubule attachment during mitosis. Centromere identity in humans is epigenetically determined, with no DNA sequence either necessary or sufficient. A prime candidate for the epigenetic mark is assembly into centromeric chromatin of centromere protein A (CENP-A), a histone H3 variant found only at functional centromeres. A new covalent fluorescent pulse-chase labeling approach using SNAP tagging has now been developed and is used to demonstrate that CENP-A bound to a mature centromere is quantitatively and equally partitioned to sister centromeres generated during S phase, thereby remaining stably associated through multiple cell divisions. Loading of nascent CENP-A on the megabase domains of replicated centromere DNA is shown to require passage through mitosis but not microtubule attachment. Very surprisingly, assembly and stabilization of new CENP-A containing nucleosomes is restricted exclusively to the subsequent G1 phase, demonstrating direct coupling between progression through mitosis and assembly/maturation of the next generation of centromeres. PMID- 17339381 TI - Centromeric chromatin gets loaded. AB - Centromeric nucleosomes contain a histone H3 variant called centromere protein A (CENP-A) that is required for kinetochore assembly and chromosome segregation. Two new studies, Jansen et al. (see p. 795 of this issue) and Maddox et al. (see p. 757 of this issue), address when CENP-A is deposited at centromeres during the cell division cycle and identify an evolutionally conserved protein required for CENP-A deposition. Together, these studies advance our understanding of centromeric chromatin assembly and provide a framework for investigating the molecular mechanisms that underlie the centromere-specific loading of CENP-A. PMID- 17339382 TI - To die or not to die--a role for Fork head. AB - The precise determination of when and where cells undergo programmed cell death is critical for normal development and tissue homeostasis. Cao et al. (2007; see p. 843 of this issue) report that the Fork head (Fkh) transcription factor, which is essential for the early development and function of the larval salivary glands in Drosophila melanogaster, also contributes to its demise. These authors show that fkh expression in the salivary glands is normally lost at puparium formation, which is approximately 12 h before they undergo massive cell death triggered by the steroid hormone ecdysone, making room for their developing adult counterparts. The loss of Fkh eliminates its role in blocking cell death, allowing for subsequent ecdysone-induced reaper and head involution defective death activator expression and tissue destruction. This study provides new insights into the transcriptional regulation of programmed cell death and the mechanisms that underlie the precise spatial and temporal control of hormone responses during development. PMID- 17339383 TI - Effect of tuberculosis on the survival of women infected with human immunodeficiency virus. AB - Evidence regarding the effect of tuberculosis (TB) disease on progression of human immunodeficiency virus (HIV) disease is inconclusive. The authors estimated the effect of time-varying incident TB on time to acquired immunodeficiency syndrome (AIDS)-related mortality using a joint marginal structural Cox model. Between 1995 and 2002, 1,412 HIV type 1 (HIV-1)-infected women enrolled in the Women's Interagency HIV Study were followed for a median of 6 years. Twenty-nine women incurred incident TB, and 222 died of AIDS-related causes. Accounting for age, CD4 cell count, HIV-1 RNA level, serum albumin level, and non-TB AIDS at study entry, as well as for time-varying CD4 cell count, CD4 cell count nadir, HIV-1 RNA level, peak HIV-1 RNA level, serum albumin level, HIV-related symptoms, non-TB AIDS, anti-Pneumocystis jiroveci prophylaxis, antiretroviral therapy, and household income, the hazard ratio for AIDS-related death comparing time after incident TB with time before incident TB was 4.0 (95% confidence interval (CI): 1.2, 14). The effect of incident TB on mortality was similar among highly active antiretroviral therapy (HAART)-exposed women (hazard ratio = 4.3, 95% CI: 0.9, 22) and non-HAART-exposed women (hazard ratio = 3.9, 95% CI: 0.9, 17; interaction p = 0.91). Although results were imprecise because few women incurred TB, irrespective of HAART exposure, incident TB increases the hazard of AIDS-related death among HIV-infected women. PMID- 17339384 TI - Is 2,3,5-pyrroletricarboxylic acid in hair a better risk indicator for melanoma than traditional epidemiologic measures for skin phenotype? AB - This study aims to assess type of melanin as a risk indicator for skin tumors, in a sample of melanoma cases and controls within a larger multicenter study (Helios 2), held in Europe and South America in 2001-2002. In each case and control, the melanin content in hair was assessed by three methods: 1) the amount of 2,3,5 pyrroletricarboxylic acid (PTCA); 2) the absorbance ratio with ultraviolet spectroscopy; and 3) the spectra of near-infrared spectroscopy. Statistical analysis was performed in a Bayesian setting, defining priors for confounders and effect modifiers from the larger study data set. Subjects with values of PTCA of less than 85 ng/mg carried an increased risk (26 vs. seven discordant pairs: odds ratio = 4.4, 95% confidence interval: 1.52, 14.54), adjusted by hair color, eye color, and number of nevi (n = > or =40). The absorbance ratio showed a weaker and nonsignificant odds ratio of 1.5. After correction by misclassification, near infrared spectroscopy was associated with an odds ratio of 2.3 (95% confidence interval: 1.36, 4.22). The amount of PTCA is thus a strong and independent risk indicator for melanoma. Incorporating PTCA determination into epidemiologic studies is therefore recommended. PMID- 17339385 TI - Neuromotor outcome at 2 years of very preterm infants who were treated with high frequency oscillatory ventilation or conventional ventilation for neonatal respiratory distress syndrome. AB - OBJECTIVE: In a previous multicenter, randomized trial, elective use of high frequency oscillatory ventilation was compared with the use of conventional ventilation in the management of respiratory distress syndrome in preterm infants <30 weeks. No difference in terms of respiratory outcome was observed, but concerns were raised about an increased rate of severe intraventricular hemorrhage in the high-frequency ventilation group. To evaluate outcome, a follow up study was conducted until a corrected age of 2 years. We report the results concerning neuromotor outcome. METHODS: Outcome was able to be evaluated in 192 of the 212 infants who survived until discharge from the neonatal unit: 97 of 105 infants of the high-frequency group and 95 of 104 infants of the conventional ventilation group. RESULTS: In the infants reviewed, mean birth weight and gestational age were similar in the 2 ventilation groups. As in the overall study population, the following differences were observed between the high-frequency ventilation group and the conventional ventilation group: lower 5-minute Apgar score, fewer surfactant instillations, and a higher incidence of severe intraventricular hemorrhage. At a corrected age of 2 years, 93 of the 97 infants of the high-frequency group and 79 of the 95 infants of the conventional ventilation group did not present any neuromotor disability, whereas 4 infants of the high-frequency group and 16 infants of the conventional ventilation group had cerebral palsy. CONCLUSIONS: Contrary to our initial concern about the increased rate of severe intraventricular hemorrhage in the high-frequency ventilation group, these data suggest that early use of high-frequency ventilation, compared with conventional ventilation, may be associated with a better neuromotor outcome. Because of the small number of patients studied and the absence of any explanation for this finding, we can conclude only that high-frequency oscillatory ventilation is not associated with a poorer neuromotor outcome. PMID- 17339386 TI - Performance of a career development and compensation program at an academic health science center. AB - OBJECTIVE: The academic physicians of our department developed a novel Career Development and Compensation Program to outline job expectations, enhance career development, and provide a peer-review process to assess performance. The Career Development and Compensation Program was founded on the principle that sustained achievement in education, clinical care, or research should be valued, supported, and rewarded in an equivalent manner and that reward for clinical work should not be limited by the focus of the university on research and education. The objective of this study was to determine whether the principles of the Career Development and Compensation Program were sustained during the initial 7 years of its implementation. METHODS: The outcome of the 7 triennial reviews that occurred from 1999 to 2005 was evaluated. For the purposes of some analyses, physicians were classified as predominately clinical (clinician-specialists and clinician teachers), predominately education (clinician-educators), or predominately research (clinician-investigators and clinician-scientists). RESULTS: Each of the job profiles had a similar probability to increase a level within the Career Development and Compensation Program at the time of triennial review. Similarly, all 5 job profiles had a similar rate of increase in their level in relation to the total number of years of experience at an academic health science center. Neither the university academic rank nor gender of the physician affected the probability of increasing a level at the time of the triennial review. CONCLUSION: The peer-reviewed Career Development and Compensation Program recognizes sustained achievement in each area of education, clinical care, and research in an equivalent manner with no detectable effect of academic rank or gender. PMID- 17339387 TI - Preterm birth-associated cost of early intervention services: an analysis by gestational age. AB - OBJECTIVES: Characterizing the cost of preterm birth is important in assessing the impact of increasing prematurity rates and evaluating the cost-effectiveness of therapies to prevent preterm delivery. To assess early intervention costs that are associated with preterm births, we estimated the program cost of early intervention services for children who were born in Massachusetts, by gestational age at birth. METHODS: Using the Pregnancy to Early Life Longitudinal Data Set, birth certificates for infants who were born in Massachusetts between July 1999 and June 2000 were linked to early intervention claims through 2003. We determined total program costs, in 2003 dollars, of early intervention and mean cost per surviving infant by gestational age. Costs by plurality, eligibility criteria, provider discipline, and annual costs for children's first 3 years also were examined. RESULTS: Overall, 14,033 of 76,901 surviving infants received early intervention services. Program costs totaled almost $66 million, with mean cost per surviving infant of $857. Mean cost per infant was highest for children who were 24 to 31 weeks' gestational age ($5393) and higher for infants who were 32 to 36 weeks' gestational age ($1578) compared with those who were born at term ($725). Cost per surviving infant generally decreased with increasing gestational age. Among children in early intervention, mean cost per child was higher for preterm infants than for term infants. At each gestational age, mean cost per surviving infant was higher for multiples than for singletons, and annual early intervention costs were higher for toddlers than for infants. CONCLUSIONS: Compared with their term counterparts, preterm infants incurred higher early intervention costs. This information along with data on birth trends will inform budget forecasting for early intervention programs. Costs that are associated with early childhood developmental services must be included when considering the long-term costs of prematurity. PMID- 17339388 TI - Clicker evolution: seeking intelligent design. AB - Two years after the first low-cost radio-frequency audience response system using clickers was introduced for college classrooms, at least six different systems are on the market. Their features and user-friendliness are evolving rapidly, driven by competition and improving technology. The proliferation of different systems is putting pressure on universities to standardize or otherwise limit the number of different clickers a student is expected to acquire. To facilitate that choice, the strengths and weaknesses of six systems (eInstruction Classroom Performance System, Qwizdom, TurningPoint, Interwrite PRS, iClicker, and H-ITT) are compared, and the factors that should be considered in making a selection are discussed. In our opinion, the selection of a clicker system should be driven by the faculty, although students and the relevant teaching and technology support units of the university must also participate in the dialogue. Given the pace of development, it is also wise to reconsider the choice of a clicker system at regular intervals. PMID- 17339389 TI - Clickers in the large classroom: current research and best-practice tips. AB - Audience response systems (ARS) or clickers, as they are commonly called, offer a management tool for engaging students in the large classroom. Basic elements of the technology are discussed. These systems have been used in a variety of fields and at all levels of education. Typical goals of ARS questions are discussed, as well as methods of compensating for the reduction in lecture time that typically results from their use. Examples of ARS use occur throughout the literature and often detail positive attitudes from both students and instructors, although exceptions do exist. When used in classes, ARS clickers typically have either a benign or positive effect on student performance on exams, depending on the method and extent of their use, and create a more positive and active atmosphere in the large classroom. These systems are especially valuable as a means of introducing and monitoring peer learning methods in the large lecture classroom. So that the reader may use clickers effectively in his or her own classroom, a set of guidelines for writing good questions and a list of best-practice tips have been culled from the literature and experienced users. PMID- 17339390 TI - Seeing cells on the web. PMID- 17339391 TI - Leadership Summit to Effect Change in Teaching and Learning: undergraduate education in agriculture. PMID- 17339392 TI - Assessment of the effects of student response systems on student learning and attitudes over a broad range of biology courses. AB - With the advent of wireless technology, new tools are available that are intended to enhance students' learning and attitudes. To assess the effectiveness of wireless student response systems in the biology curriculum at New Mexico State University, a combined study of student attitudes and performance was undertaken. A survey of students in six biology courses showed that strong majorities of students had favorable overall impressions of the use of student response systems and also thought that the technology improved their interest in the course, attendance, and understanding of course content. Students in lower-division courses had more strongly positive overall impressions than did students in upper division courses. To assess the effects of the response systems on student learning, the number of in-class questions was varied within each course throughout the semester. Students' performance was compared on exam questions derived from lectures with low, medium, or high numbers of in-class questions. Increased use of the response systems in lecture had a positive influence on students' performance on exam questions across all six biology courses. Students not only have favorable opinions about the use of student response systems, increased use of these systems increases student learning. PMID- 17339393 TI - Using the web to encourage student-generated questions in large-format introductory biology classes. AB - Students rarely ask questions related to course content in large-format introductory classes. The use of a Web-based forum devoted to student-generated questions was explored in a second-semester introductory biology course. Approximately 80% of the enrolled students asked at least one question about course content during each of three semesters during which this approach was implemented. About 95% of the students who posted questions reported reading the instructor's response to their questions. Although doing so did not contribute to their grade in the course, approximately 75% of the students reported reading questions posted by other students in the class. Approximately 60% of the students reported that the Web-based question-asking activity contributed to their learning of biology. PMID- 17339394 TI - What good is a scientist in the classroom? Participant outcomes and program design features for a short-duration science outreach intervention in K-12 classrooms. AB - Many short-duration science outreach interventions have important societal goals of raising science literacy and increasing the size and diversity of the science workforce. Yet, these long-term outcomes are inherently challenging to evaluate. We present findings from a qualitative research study of an inquiry-based, life science outreach program to K-12 classrooms that is typical in design and excellent in execution. By considering this program as a best case of a common outreach model, the "scientist in the classroom," the study examines what benefits may be realized for each participant group and how they are achieved. We find that K-12 students are engaged in authentic, hands-on activities that generate interest in science and new views of science and scientists. Teachers learn new science content and new ways to teach it, and value collegial support of their professional work. Graduate student scientists, who are the program presenters, gain teaching and other skills, greater understanding of education and diversity issues, confidence and intrinsic satisfaction, and career benefits. A few negative outcomes also are described. Program elements that lead to these benefits are identified both from the research findings and from insights of the program developer on program design and implementation choices. PMID- 17339395 TI - Exploring DNA structure with Cn3D. AB - Researchers in the field of bioinformatics have developed a number of analytical programs and databases that are increasingly important for advancing biological research. Because bioinformatics programs are used to analyze, visualize, and/or compare biological data, it is likely that the use of these programs will have a positive impact on biology education. Over the past years, we have been working to help biology instructors introduce bioinformatics activities into their curricula by providing them with instructional materials that use bioinformatics programs and databases as educational tools. In this study, we measured the impact of a set of these materials on student learning. The activities in these materials asked students to use the molecular structure visualization program Cn3D to locate, identify, or analyze diverse features in DNA structures. Both the experimental groups of college and high school students showed significant increases in learning relative to control groups. Further, learning gains by the college students were correlated with the number of activities assigned. We conclude that working with Cn3D was important for improving student understanding of DNA structure. This study is one example of how a bioinformatics program for visualization can be used to support student learning. PMID- 17339396 TI - A summer program designed to educate college students for careers in bioinformatics. AB - A summer program was created for undergraduates and graduate students that teaches bioinformatics concepts, offers skills in professional development, and provides research opportunities in academic and industrial institutions. We estimate that 34 of 38 graduates (89%) are in a career trajectory that will use bioinformatics. Evidence from open-ended research mentor and student survey responses, student exit interview responses, and research mentor exit interview/survey responses identified skills and knowledge from the fields of computer science, biology, and mathematics that are critical for students considering bioinformatics research. Programming knowledge and general computer skills were essential to success on bioinformatics research projects. General mathematics skills obtained through current undergraduate natural sciences programs were adequate for the research projects, although knowledge of probability and statistics should be strengthened. Biology knowledge obtained through the didactic phase of the program and prior undergraduate education was adequate, but advanced or specific knowledge could help students progress on research projects. The curriculum and assessment instruments developed for this program are available for adoption by other bioinformatics programs at http://www.calstatela.edu/SoCalBSI. PMID- 17339397 TI - Chemokines as modulators of neuroendocrine functions. AB - Chemokines are small secreted proteins with chemoattractant properties for immune cells. Besides their role in the immune system, chemokines and their receptors may play important roles in the central nervous system. Neurodegenerative disorders that involve neuroinflammation such as multiple sclerosis, stroke, Alzheimer's disease, Parkinson's disease and HIV-associated dementia are commonly associated with local upregulation and release of chemokines. However, recent work has established that certain chemokines, constitutively expressed in the brain, exert functions in the brain that are distinct from inflammation. These chemokines regulate neuronal migration during brain development, modulate neuronal activity and play a role in various neurodegenerative diseases, pain and more recently in neuroendocrine functions. All these novel aspects, mainly focused on the chemokine stromal cell-derived factor-1/CXCL12 and its receptor CXCR4, were presented by pioneers in the field during the symposium held at the sixth International Congress of Neuroendocrinology in Pittsburgh, Pennsylvania, USA in June 2006. PMID- 17339398 TI - Chemokines and chemokine receptors in the brain: implication in neuroendocrine regulation. AB - Chemokines are small secreted proteins that chemoattract and activate immune and non-immune cells both in vivo and in vitro. In addition to their well-established role in the immune system, several recent reports have suggested that chemokines and their receptors may also play a role in the central nervous system (CNS). The best known central action is their ability to act as immunoinflammatory mediators. Indeed, these proteins regulate leukocyte infiltration in the brain during inflammatory and infectious diseases. However, we and others recently demonstrated that they are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. The goal of this review is to highlight the role of chemokines in the control of neuroendocrine functions. First, we will focus on the expression of chemokines and their receptors in the CNS, with the main spotlight on the neuronal expression in the hypothalamo-pituitary system. Secondly, we will discuss the role--we can now suspect--of chemokines and their receptors in the regulation of neuroendocrine functions. In conclusion, we propose that chemokines can be added to the well-described neuroendocrine regulatory mechanisms, providing an additional fine modulatory tuning system in physiological conditions. PMID- 17339399 TI - Multiple actions of the chemokine stromal cell-derived factor-1alpha on neuronal activity. AB - The chemokine SDF-1alpha and its cognate receptor CXCR4 are expressed in several neuronal populations. This review focuses on our current knowledge about the actions of this chemokine on neuronal excitability, through CXCR4 or other yet unknown pathways. In various neuronal populations (CA1 neurons of the hippocampus, granular and Purkinje cells of the cerebellum, melanin-concentrating hormone neurons of the lateral hypothalamus, vasopressinergic neurons of the supraoptic and the paraventricular nucleus of the hypothalamus, and dopaminergic neurons of the substantia nigra), SDF-1alpha can modulate the activity of neurons by multiple regulatory pathways including and often combining: (i) modulation of voltage-dependent channels (sodium, potassium, and calcium), (ii) activation of the G-protein-activated inward rectifier potassium current, and (iii) increase in neurotransmitter release (gamma-amino butyric acid (GABA), glutamate, and dopamine), often through Ca-dependent mechanisms. The possible mechanisms underlying these effects and their consequences in terms of modulation of neuroendocrine systems and physiopathology are discussed. PMID- 17339400 TI - CXC chemokine receptor 4 regulates neuronal migration and axonal pathfinding in the developing nervous system: implications for neuronal regeneration in the adult brain. AB - Chemotactic cytokines (chemokines) are small secreted proteins that control leukocyte trafficking in immune organs. Chemokines which are induced in the brain during conditions of inflammation play a role in the local immune response. Recently, it has been established in the rodent brain that distinct chemokines and chemokine receptors are constitutively expressed by neurons and that these chemokines modulate neuronal functions. The CXC motif chemokine stromal cell derived factor-1 (SDF-1), CXCL12 together with its cognate receptor CXCR4 represents the best-characterized neuronal chemokine system. Transwell migration assays with neuronal precursors, pharmacological manipulation of CXCR4 signaling in embryonic brain explants, and histochemical studies of SDF-1- or CXCR4 deficient mouse embryos provide proof that SDF-1 directs neuronal migration and axonal pathfinding in the developing nervous system. In the adult brain, SDF-1 is thought to influence neurogenesis as well as recruitment of brain resident and non-resident circulating cells toward sites of lesion. The present review summarizes patterns and functions of the SDF-1/CXCR4 system in the rodent brain with a focus on the developing and adult cerebral cortex. PMID- 17339401 TI - Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function. AB - Chemokines are key factors involved in the regulation of immune response, through the activation and control of leukocyte traffic, lymphopoiesis and immune surveillance. However, a large number of chemokines and their receptors are expressed in central nervous system (CNS) cells, either constitutively or induced by inflammatory stimuli, playing a role in many neuropathological processes. Stromal cell-derived factor 1 (SDF1) is a chemokine whose extra-immunological localization and functions have been extensively studied. SDF1 and its receptor CXCR4 were identified in both neurons and glia of many brain areas, including the hypothalamus, as well as at the pituitary level. Importantly, SDF1 and CXCR4 expression is increased in brain tumors in which their activity induced tumor cell proliferation and brain parenchyma invasion. Despite their localization, to date very few reports addressed the role of CXCR4 and SDF1 in the modulation of the hypothalamus/pituitary axis and their possible involvement in the development of pituitary adenomas. In this review, we discuss previous literature data on the role of chemokines in normal and adenomatous pituitary cells, focusing on recent data from our group showing that CXCR4 activation controls proliferation and both prolactin and GH release in the pituitary adenoma cell line GH4C1 through a complex network of intracellular signals. Thus, the SDF1/CXCR4 system together with other chemokinergic ligand-receptor pairs, may represent a novel regulatory pathway for pituitary function and, possibly, be involved in pituitary adenoma development. These lines of evidence suggest that the inhibition of chemokine receptors may represent a novel pharmacological target for the treatment of pituitary adenomas. PMID- 17339402 TI - Multiple peroxisome proliferator-activated receptor beta subtypes from Atlantic salmon (Salmo salar). AB - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily that functions as critical regulators of lipid and energy homeostasis. Although intensively studied in mammals, their basic biological functions are still poorly understood. The objective of this work was to characterize PPARbeta subtypes in a fish, the Atlantic salmon (Salmo salar), in order to address PPAR function and the regulation of lipid homeostasis in lower vertebrates. The screening of an Atlantic salmon genomic library revealed the presence of four genes for PPARbeta subtypes. Based on comparisons of exons and exon-flanking regions, these genes were assigned into two families, ssPPARbeta1 and ssPPARbeta2, each family containing two isotypes: ssPPARbeta1A and beta1B and ssPPARbeta2A and beta2B. Two full-length cDNAs for ssPPARbeta1A and ssPPPARbeta2A were isolated. Transcripts for ssPPARbeta1A and ssPPARbeta2A have distinct tissue expression profiles, with ssPPARbeta1A predominating in liver and ssPPARbeta2A predominating in gill. Expression levels of mRNA of either isotypes were up to tenfold lower in kidney, heart, spleen, muscle, and brain. In cellular transfection assays, ssPPARbeta1A is activated by monounsaturated fatty acids, 2-bromopalmitate, and mammalian PPARbeta-specific ligand GW501516. In contrast, PPARbeta2A was not activated by any of the compounds tested. Furthermore, ssPPARbeta2A repressed both the basal reporter gene activity and the GW501516-induced activity of ssPPARbeta1A. The results indicate unexpected levels of variety and complexity in PPAR subtype and mechanism of action in lower vertebrates. PMID- 17339403 TI - Histone deacetylase inhibition and progesterone act synergistically to stimulate baboon glycodelin gene expression. AB - During the late luteal phase of the menstrual cycle and early pregnancy, the major secretory product of the uterine glandular epithelial cells in humans and non-human primates is glycodelin. Previous studies using Ishikawa cells, a human endometrial cell line, have shown that a chimeric plasmid containing the baboon glycodelin promoter responds to progestins but the response is modest compared with the induction of glycodelin seen in vivo and in gene array analysis. A recent report indicating that the histone deacetylase inhibitor trichostatin A (TSA) promoted glycodelin expression prompted us to examine its mechanism of action. In Ishikawa cells transfected with the baboon glycodelin promoter, TSA and the synthetic progestin medroxyprogesterone acetate both stimulated expression of the reporter and the combined treatment produced a synergistic effect. The effect of TSA and progestin was absent when the same promoter constructs were transfected into COS-1 cells, a kidney cell line, and a TSA effect but no progestin effect was observed in T47D cells, a mammary cell line. Through deletion analysis, the TSA action was localized to the -67/-52 region of the baboon glycodelin promoter, a region which contains the proximal Sp1 site. Deletions of this same region had no effect on progestin responsiveness. Our findings indicate that at least two regions of the glycodelin promoter are important for the normal induction of glycodelin expression. Non-target cells may lack factors which act on the response elements resulting in the restriction of expression to the appropriate target tissue. PMID- 17339404 TI - Identification and subcellular localization of the Na+/H+ exchanger and a novel related protein in the endocrine pancreas and adrenal medulla. AB - Na+/H+ exchangers (NHE) constitute a family of membrane antiporters that contribute to the regulation of cellular pH and volume in many tissues, including pancreatic islets. We investigated the molecular identity of NHE in rodent and human endocrine pancreas, and determined its cellular and subcellular localization. NHE1 was the most abundantly expressed isoform in rat islets, and was also expressed in mouse and human islets. By western blot, an antiserum raised against the C-terminus end of NHE1 confirmed the presence of a ~100 kDa protein corresponding to NHE1 in islets and unexpectedly unveiled the existence of a ~65 kDa cross-reactive NHE1-related protein. By immunohistochemistry, the antiserum labelled the membranes of pancreatic acini and ducts, but also diffusely stained the cytoplasm of insulin, glucagon and somatostatin cells as well as endocrine cells of the adrenal medulla. Electron microscopy localized the NHE1 immunoreactivity in the membrane of secretory granules, an unexpected finding supported by a decrease in immunohistochemical signal in degranulated beta-cells. Islets of Slc9A1(swe/swe) mice, which lack full NHE1 protein, were found to express an mRNA corresponding to the 3' end of NHE1 as well as the ~65 kDa protein. They still showed the cytoplasmic labelling but no plasma membrane was stained. We conclude that both the full-length and the shorter-splice variant of NHE1 are expressed in all cell types of the endocrine pancreas and in the adrenal medulla of rodents and humans. The complete protein is addressed to the plasma membrane and the shorter one to the membrane of secretory granules where its function remains to be established. PMID- 17339406 TI - The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. AB - Perivascular microglia activation is a hallmark of inflammatory demyelination in multiple sclerosis (MS), but the mechanisms underlying microglia activation and specific strategies to attenuate their activation remain elusive. Here, we identify fibrinogen as a novel regulator of microglia activation and show that targeting of the interaction of fibrinogen with the microglia integrin receptor Mac-1 (alpha(M)beta(2), CD11b/CD18) is sufficient to suppress experimental autoimmune encephalomyelitis in mice that retain full coagulation function. We show that fibrinogen, which is deposited perivascularly in MS plaques, signals through Mac-1 and induces the differentiation of microglia to phagocytes via activation of Akt and Rho. Genetic disruption of fibrinogen-Mac-1 interaction in fibrinogen-gamma(390-396A) knock-in mice or pharmacologically impeding fibrinogen Mac-1 interaction through intranasal delivery of a fibrinogen-derived inhibitory peptide (gamma(377-395)) attenuates microglia activation and suppresses relapsing paralysis. Because blocking fibrinogen-Mac-1 interactions affects the proinflammatory but not the procoagulant properties of fibrinogen, targeting the gamma(377-395) fibrinogen epitope could represent a potential therapeutic strategy for MS and other neuroinflammatory diseases associated with blood-brain barrier disruption and microglia activation. PMID- 17339405 TI - Stromal cell-derived factor 1 promotes angiogenesis via a heme oxygenase 1 dependent mechanism. AB - Stromal cell-derived factor 1 (SDF-1) plays a major role in the migration, recruitment, and retention of endothelial progenitor cells to sites of ischemic injury and contributes to neovascularization. We provide direct evidence demonstrating an important role for heme oxygenase 1 (HO-1) in mediating the proangiogenic effects of SDF-1. Nanomolar concentrations of SDF-1 induced HO-1 in endothelial cells through a protein kinase C zeta-dependent and vascular endothelial growth factor-independent mechanism. SDF-1-induced endothelial tube formation and migration was impaired in HO-1-deficient cells. Aortic rings from HO-1(-/-) mice were unable to form capillary sprouts in response to SDF-1, a defect reversed by CO, a byproduct of the HO-1 reaction. Phosphorylation of vasodilator-stimulated phosphoprotein was impaired in HO-1(-/-) cells, an event that was restored by CO. The functional significance of HO-1 in the proangiogenic effects of SDF-1 was confirmed in Matrigel plug, wound healing, and retinal ischemia models in vivo. The absence of HO-1 was associated with impaired wound healing. Intravitreal adoptive transfer of HO-1-deficient endothelial precursors showed defective homing and reendothelialization of the retinal vasculature compared with HO-1 wild-type cells following ischemia. These findings demonstrate a mechanistic role for HO-1 in SDF-1-mediated angiogenesis and provide new avenues for therapeutic approaches in vascular repair. PMID- 17339408 TI - Early embryonic survival and embryo development in two lines of rabbits divergently selected for uterine capacity. AB - The aim of this work is to study early embryo survival and development in 2 lines divergently selected for high and low uterine capacity throughout 10 generations. A total of 162 female rabbits from the high line and 133 from the low line were slaughtered at 25, 48, or 62 h of gestation. There were no differences in ovulation rate and fertilization rate between lines in any of the 3 stages of gestation. Embryo survival, estimated as the number of normal embryos recovered at a constant ovulation rate, was similar in both lines at 25 and 48 h. Embryo survival was greater in the high line [D (posterior mean of the difference between the high and low lines) = 0.57 embryos] at 62 h of gestation. There was no difference in embryonic stage of development at 25 h, but at 48 and 62 h of gestation, the high line, compared with the low line, had a greater percentage of early morulae (83 vs. 72%) and compacted morulae (55 vs. 38%). Divergent selection for uterine capacity appeared to modify embryo development, at least from 48 h of gestation, and embryo survival from 62 h. PMID- 17339407 TI - Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice. AB - Sustained pressure overload causes cardiac hypertrophy and the transition to heart failure. We show here that dietary supplementation with physiologically relevant levels of copper (Cu) reverses preestablished hypertrophic cardiomyopathy caused by pressure overload induced by ascending aortic constriction in a mouse model. The reversal occurs in the continued presence of pressure overload. Sustained pressure overload leads to decreases in cardiac Cu and vascular endothelial growth factor (VEGF) levels along with suppression of myocardial angiogenesis. Cu supplementation replenishes cardiac Cu, increases VEGF, and promotes angiogenesis. Systemic administration of anti-VEGF antibody blunts Cu regression of hypertrophic cardiomyopathy. In cultured human cardiomyocytes, Cu chelation blocks insulin-like growth factor (IGF)-1- or Cu stimulated VEGF expression, which is relieved by addition of excess Cu. Both IGF 1 and Cu activate hypoxia-inducible factor (HIF)-1alpha and HIF-1alpha gene silencing blocks IGF-1- or Cu-stimulated VEGF expression. HIF-1alpha coimmunoprecipitates with a Cu chaperone for superoxide dismutase-1 (CCS), and gene silencing of CCS, but not superoxide dismutase-1, prevents IGF-1- or Cu induced HIF-1alpha activation and VEGF expression. Therefore, dietary Cu supplementation improves the condition of hypertrophic cardiomyopathy at least in part through CCS-mediated HIF-1alpha activation of VEGF expression and angiogenesis. PMID- 17339409 TI - Putative urinary pheromone of bulls involved with breeding performance of primiparous beef cows in a progestin-based estrous synchronization protocol. AB - The objective of this study was to determine if factors associated with the biostimulatory effect of bulls alter breeding performance of primiparous, suckled beef cows using a progestin-based estrous synchronization protocol. We tested the hypotheses that the estrous synchronization response and AI pregnancy rates differ among cows exposed to bulls, continuously exposed to bull urine, and exposed to fence-line contact with bulls or cows not exposed to bulls or bull urine. Data were collected from 3 experiments performed over consecutive years. Cows were assigned to the following treatments: bull exposure (BE; n = 26) or no bull exposure (NB; n = 25) in Exp. 1, bull urine exposure (BUE; n = 19) or steer urine exposure (SUE; n = 19) in Exp. 2, and fence-line contact with bulls (BFL; n = 26) or no bull exposure (NB; n = 26) in Exp. 3. Synchronization protocols in each experiment included the use of a controlled internal drug release device (d 10), PGF(2alpha) (d -3), and GnRH and fixed-time AI (TAI; d 0). Cows that were observed in estrus by 60 h after PGF(2alpha) were inseminated 12 h later. Cows not observed in estrus by 60 h after PGF(2alpha) were TAI at 72 h and given GnRH (100 mug). Pregnancy was determined by ultrasonography 35 d after TAI. In Exp. 1, 2, and 3, cows were exposed directly to bulls, bull urine, or bull fence-line contact for 35, 64, and 42 d, respectively. Data were analyzed between treatments within each experiment. The proportion of estrous cycling cows did not differ between treatments at the beginning of each experiment; however, more (P < 0.05) BE and BFL cows were estrous cycling at the beginning of the estrous synchronization protocol than NB cows in Exp. 1 and 3. The proportion of cows that showed estrus and interval to estrus after PGF(2alpha) did not differ between treatments in Exp. 1 and 3. However, in Exp. 2, more BUE cows tended (P = 0.09) to have shorter intervals to estrus and to exhibit estrus after PGF(2alpha) than SUE cows. Overall, AI pregnancy rates were greater (P < 0.05) for BE and BUE cows than for NB and SUE cows in Exp. 1 and 2, respectively. There was no difference in AI pregnancy rates between BFL and NB cows in Exp. 3. The presence of bulls and exposure to bull urine appeared to improve breeding performance of primiparous beef cows using a progestin-based estrous synchronization protocol, whereas fence-line bull exposure was insufficient to cause this biostimulatory effect. We propose that a novel urinary pheromone of bulls may be responsible for the enhancement of fertility in the primiparous, postpartum cow. PMID- 17339411 TI - Across-breed adjustment factors for expected progeny differences for carcass traits. AB - Adjustment factors to allow comparison of EPD from several breed associations for birth, weaning, and yearling weights have been available for more than 10 yr. This paper describes steps to calculate adjustment factors for EPD for 4 carcass traits: marbling score, fat thickness, ribeye area, and retail product percentage. The required information is the same as for the weight traits: 1) breed of sire solutions based on measurements on progeny at the US Meat Animal Research Center (USMARC) that have sires with breed association EPD, 2) mean EPD of sires weighted by number of progeny at USMARC (USMARC progeny not included in breed association EPD), and 3) mean EPD of nonparents from breed associations (defined as animals born 2 yr prior to calculation of EPD). Records at USM-ARC are adjusted to 100% heterozygosity because the purpose of the adjustment factors is to allow prediction of performance of progeny of sires mated to other breeds of dam. A critical step is to adjust breed of sire solutions, which are based on an earlier sample of sires, to the equivalent of a sample from a more recent nonparent group using the difference between mean EPD from information sources 2) and 3). The difference is multiplied by the coefficient of regression of USMARC progeny on EPD of their sires. With weight traits, these coefficients are not greatly different from unity. With the carcass traits, 2 sets of coefficients can be used depending on whether the EPD are based on carcass or ultrasound measurements. The regression coefficients also reflect differences in conditions for USMARC progeny (all steers) and factors associated with breed association EPD. Only for marbling score and ribeye area were any estimates of the regression coefficients near unity. For other traits, the coefficients ranged from 1.65 to 2.82. The solutions for breed of sire, differences in mean EPD, and regression coefficients are then used to calculate adjustment factors for EPD of 11 breeds including the arbitrary base breed, Angus. PMID- 17339410 TI - Distribution of supplemental Escherichia coli AppA2 phytase activity in digesta of various gastrointestinal segments of young pigs. AB - The objective of this study was to determine the functional location and disappearance of activity of a supplemental Escherichia coli AppA2 phytase and its impact on digesta P and Ca concentrations in the gastrointestinal tract of pigs. In Exp. 1, 18 pigs (8.3 +/- 0.2 kg of BW) were allotted to 3 groups (n = 6 each) and fed a low-P (0.4%) corn-soybean meal, basal diet (BD), BD + phytase [500 units (U)/kg of feed], or BD + inorganic P (iP, 0.1%) for 4 wk. In Exp. 2, 30 pigs (14.5 +/- 0.2 kg of BW) were allotted to 3 groups (n = 10 each) and fed BD, BD + 500 U of phytase/kg of feed, or BD + 2,000 U of phytase/kg of feed for 2 wk. Five or six pigs from each treatment group were killed at the end of both experiments to assay for digesta phytase activity and soluble P concentration in 6 segments of the digestive tract and digesta total P and Ca concentrations in stomach and colon. Compared with pigs fed BD, pigs fed BD + 500 U of phytase/kg of feed in Exp. 1 and BD + 2,000 U of phytase/kg of feed in Exp. 2 had greater (P < 0.05) phytase activities in the digesta of the stomach and upper jejunum (2 m aborally from the duodenum). No phytase activity was detected in the digesta of the lower jejunum (2.12 m cranial to the ileocecal junction) or ileum from any of the treatment groups in either trial. Concentrations of digesta-soluble P peaked in the upper jejunum of pigs fed BD in Exp. 1 and 2, but showed gradual decreases between the stomach and the upper jejunum of pigs fed BD + phytase or BD + iP. In both experiments, pigs fed only BD had greater (P < 0.05) colonic digesta phytase activity and soluble P concentrations than those fed phytase. In Exp. 2, total colonic digesta P or Ca concentrations, or both, of pigs displayed a phytase-dose dependent reduction (P < 0.05). In conclusion, supplemental dietary AppA2 mainly functioned in the stomach and was associated with a reduced phytase activity in colonic digesta of weanling pigs. PMID- 17339412 TI - Reaction of foster cows to prevention of suckling from and separation from four calves simultaneously or in two steps. AB - The aim of this study was to investigate if a 2-step method of preventing suckling and cow-calf separation reduces the stress reaction in foster cows compared with a simultaneous separation method. Seven Swedish Holstein and 5 Swedish Red dairy cows were used as foster cows, each having a group of 4 calves. The foster cow-calf group was formed when calves were 1 wk old, and the calves were prevented from suckling at 10 wk of age. In 6 of the cow-calf groups, calves were prevented from suckling by simultaneous separation from the cow (control). In the other 6 groups, calves were fitted with a nose-flap, which prevented them from suckling while they were kept together with the cow for another 2 wk before they were separated (2-step). The behavior of the foster cows was observed at 4 observation periods, 0 to 2, 8.5 to 9.5, 24 to 26, and 72 to 74 h after the calves were prevented from suckling (2-step), after separation (2-step), and after calves were prevented from suckling by simultaneous separation (control). For both treatments, saliva cortisol was sampled once daily for 5 d at wk 10. This was repeated at wk 12 for the 2-step treatment. Heart rate was measured with the behavioral observations. Control foster cows vocalized more (P < 0.001) and walked more (P = 0.005) than the 2-step foster cows after prevention of suckling and after separation from the calves. When control cows were separated from their calves, they more frequently (P < 0.001) held their head out of the pen than was the case with 2-step cows when separated 2 wk after prevention of suckling. The variation in heart rate was larger in the control group compared with 2-step cows at 0 to 2 h after separation/prevention of suckling (P = 0.002). No effect of treatment was found on cortisol concentration. Our conclusion is that separating the 2 events "prevention of suckling" and "separation" reduces the stress experienced by the foster cow at weaning. PMID- 17339413 TI - Selection for litter size at day five to improve litter size at weaning and piglet survival rate. AB - Selection for total number of piglets born (TNB) since 1992 has led to a significant increase in this trait in Danish Landrace and Danish Yorkshire but has also been accompanied by an increase in piglet mortality. The objective of this study was to estimate the genetic and phenotypic parameters for litter size and survival to find alternative selection criteria to improve litter size at weaning. Data from Landrace (9,300 litters) and Yorkshire (6,861 litters) were analyzed using REML based on a linear model including genetic effects of sow and service-sire. The estimates of heritability (based on the sow component) for TNB, number born alive (NBA), and number alive at d 5 after birth (N5D) and at weaning (about 3 wk, N3W) ranged from 0.066 to 0.090 in Landrace and 0.050 to 0.070 in Yorkshire. Genetic correlations between TNB and N3W were 0.289 in Landrace and 0.561 in Yorkshire, but between N5D and N3W the estimated genetic correlation was 0.995 in both populations. The approximate estimates of heritability for survival rate per litter at birth (SVB = NBA/TNB), from birth to d 5 (SV5 = N5D/NBA), and from d 5 to weaning (SVW = N3W/N5D) were 0.130, 0.131, and 0.023, respectively, in Landrace, and 0.095, 0.043, and 0.009, respectively, in Yorkshire. Genetic correlations between TNB and survival rates at different stages were negative. On the other hand, genetic correlations between N5D and survival rates and between N3W and survival rates were strongly or moderately positive, except for the correlations with SVW in Yorkshire. The results suggest that selection for N5D could be an interesting alternative to improve litter size at weaning and piglet survival for Danish Landrace and Danish Yorkshire. PMID- 17339414 TI - Effect of dietary energy source on in vitro substrate utilization and insulin sensitivity of muscle and adipose tissues of Angus and Wagyu steers. AB - Angus (n = 8; 210 kg of BW) and 7/8 Wagyu (n = 8; 174 kg of BW) steers were used to evaluate the effects of dietary energy source on muscle and adipose tissue metabolism and insulin sensitivity. Steers were assigned to either a grain-based (corn) or hay-based (hay) diet and fed to similar final BW. At slaughter, LM and s.c. and i.m. adipose tissue samples were collected. Portions of the LM and adipose tissues were placed immediately in liquid N for later measurement of glycolytic intermediates. Fresh LM and s.c. and i.m. adipose tissues were incubated with [U-(14)C]glucose to assess glucose metabolism in vitro. All in vitro measures were in the presence of 0 or 500 ng/mL of insulin. Also, s.c. and i.m. adipose tissues were incubated with [1-(14)C]acetate to quantify lipid synthesis in vitro. Glucose-6-phosphate and fructose-6-phosphate concentrations were 12.6- and 2.4-fold greater in muscle than in s.c. and i.m. adipose tissues, respectively. Diet did not affect acetate incorporation into fatty acids (P = 0.86). Insulin did not increase conversion of glucose to CO(2), lactate, or total lipid in steers fed hay but caused an increase (per cell) of 97 to 110% in glucose conversion to CO(2), 46 to 54% in glucose conversion to lactate, and 65 to 160% in glucose conversion to total lipid content in adipose tissue from steers fed corn. On a per-cell basis, s.c. adipose tissue had 37% greater glucose oxidation than i.m. adipose (P = 0.04) and 290% greater acetate incorporation into fatty acids than i.m. adipose (P = 0.04). Insulin addition to s.c. adipose tissue from corn-fed steers failed to stimulate glucose incorporation into fatty acids, but exposing i.m. adipose tissue from corn-fed steers to insulin resulted in a 165% increase in glucose incorporation into fatty acids. These results suggest that feeding hay limited both glucose supply and tissue capacity to increase glucose utilization in response to insulin without altering acetate conversion to fatty acids. Because s.c. adipose tissue consistently utilized more acetate and oxidized more glucose than did i.m. adipose, these results suggest that hay-based diets may alter i.m. adipose tissue metabolism with less effect on s.c. adipose tissue. PMID- 17339415 TI - Effects of supplemental rumen-protected conjugated linoleic acid or corn oil on lipid content and palatability in beef cattle. AB - Thirty-six Angus x Hereford heifers were used in a 3 x 2 factorial (3 dietary treatments; 2 supplementation times) to examine the effect of dietary lipid supplementation on lipid oxidation, lipid composition, and palatability of ribeye steaks and ground beef. Lipid was supplied in the diets as corn oil or a partially rumen-protected CLA salt for 2 specific treatment periods of the final 32 or 60 d on feed, corresponding to a total time on feed of 89 or 118 d. After an initial 56-d feeding period (basal diet), the heifers were fed 1 of 3 dietary treatments (DM basis): 1) a basal diet containing 88% concentrate and 12% grass hay (CON), 2) the basal diet plus 4% corn oil (OIL), or 3) the basal diet plus 2% partially rumen-protected CLA (RPCLA) containing 31% CLA. Heifers were randomly allotted to dietary treatments at the initiation of the study and fed individually. At 48 h postmortem, the right forequarter of each carcass was fabricated into retail cuts. Steaks (2.54-cm thick) were obtained from the posterior end of the ribeye roll (NAMP 112), and beef trim was ground for all subsequent analyses. Dietary treatment did not affect (P > 0.05) lipid oxidation in ground beef or ribeye steaks. Total trans-octadecenoate fat and trans-10 octadecenoic acid content in ribeye steaks increased (P < 0.05) with RPCLA compared with CON. Total CLA and the cis-9 trans-11 isomer of CLA contents in ribeye steaks were unchanged (P > 0.05) by lipid supplementation. In ground beef, RPCLA supplementation increased (P < 0.05) the amount of trans fat and trans-10 octadecenoic acid compared with CON or OIL; supplementation of RPCLA increased (P < 0.05) the amount of CLA cis-9 trans-11 isomer and total CLA. Lipid supplementation did not alter (P > 0.05) off-flavor ratings in ground beef or ribeye steaks. Supplementation of corn oil increased (P < 0.05) total PUFA content of ribeye steaks compared with CON and RPCLA. Dietary RPCLA supplementation increased the amount of trans fat per serving (85.5 g, broiled) by 110 and 88% in ribeye steak and ground beef, respectively, and CLA cis-9 trans 11 by 58% in ground beef compared with CON. Supplementing OIL or RPCLA resulted in minimal changes in lipid oxidation and sensory attributes of steaks and ground beef. PMID- 17339416 TI - Effect of a saponin-based surfactant and aging time on ruminal degradability of flaked corn grain dry matter and starch. AB - The objectives of this study were to investigate the effect of a saponin-based surfactant, Grain Prep surfactant (GP), and hot flake aging time on starch characteristics and ruminal DM and starch degradability of steam-flaked corn grain. In 2 experiments, the moisture content of incoming corn was automatically adjusted using the Grain Prep Auto Delivery System to 19.8% (Exp. 1) and 18.5% (Exp. 2). The application rate of GP was 22 mg/kg (as-is basis). Control corn was treated with water alone. Processed corn in Exp. 2 was stored in insulated containers for 0, 4, 8, or 16 h. Flaked corn samples were incubated in the rumen of lactating dairy cows for 0, 2, 4, 6, 16, or 24 h. In Exp. 1, GP increased, compared with the control, the soluble fraction and effective degradability (ED) of DM by 17.2 and 8.6%, respectively. The ED of cornstarch was increased by 6.7%. In Exp. 2, the concentration of soluble DM and starch were increased by GP by 15 and 24% compared with the control. The ED of DM and starch were also increased by 3 and 4%, respectively. No differences in gelatinization temperatures were observed due to treatment, except that GP-treated grain had a slightly greater mean gelatinization enthalpy in Exp. 2. In a pilot study, DM degradability parameters were not affected by germination of the corn kernels. Aging of the hot flakes for up to 16 h resulted in a quadratic decrease in DM and starch ruminal degradability. The aging process affected starch gelatinization enthalpy values of flaked grain in a manner opposite to that observed for ruminal DM and starch degradation. This phenomenon was most likely explained by increased starch intramolecular associations or crystallinity associated with starch annealing, or both. This study confirmed our previous observations that Grain Prep surfactant increases flaked corn DM and starch degradability in the rumen. Because the rate of degradation was not affected by the surfactant, the increase in degradability was attributed mainly to increases in DM and starch solubility. PMID- 17339417 TI - Genetic parameters for growth and carcass traits of Brahman steers. AB - Spring-born purebred Brahman bull calves (n = 467) with known pedigrees, sired by 68 bulls in 17 private herds in Louisiana, were purchased at weaning from 1996 through 2000 to study variation in growth, carcass, and tenderness traits. After purchase, calves were processed for stocker grazing on ryegrass, fed in a south Texas feedlot, and processed in a commercial facility. Carcass data were recorded 24 h postmortem. Muscle samples and primal ribs were taken to measure calpastatin activity and shear force. An animal model was used to estimate heritability, genetic correlations, and sire EPD. Relatively high heritability estimates were found for BW at slaughter (0.59 +/- 0.16), HCW (0.57 +/- 0.15), LM area (0.50 +/- 0.16), yield grade (0.46 +/- 0.17), calpastatin enzyme activity (0.45 +/- 0.17), and carcass quality grade (0.42 +/- 0.16); moderate heritability estimates were found for hump height (0.38 +/- 0.16), marbling score (0.37 +/- 0.16), backfat thickness (0.36 +/- 0.17), feedlot ADG (0.33 +/- 0.14), 7-d shear force (0.29 +/- 0.14), and 14-d shear force (0.20 +/- 0.11); relatively low heritability estimates were found for skeletal maturity (0.10 +/- 0.10), lean maturity (0.00 +/- 0.07), and percent KPH (0.00 +/- 0.07). Most genetic correlations were between -0.50 and +0.50. Other genetic correlations were 0.74 +/- 0.27 between calpastatin activity and 7-d shear force, 0.72 +/- 0.25 between calpastatin activity and 14-d shear force, (0.90 +/- 0.30 between yield grade and 7-d shear force, and -0.82 +/- 0.27 between backfat thickness and 7-d shear force. Heritability estimates and genetic correlations for most traits were similar to estimates reported in the literature. Sire EPD ranges for carcass traits approached those reported for sires in other breeds. The magnitude of heritability estimates suggests that improvement in carcass yield, carcass quality, and consumer acceptance traits can be made within the Brahman population. PMID- 17339418 TI - Friend of GATA-1-independent transcriptional repression: a novel mode of GATA-1 function. AB - The GATA-1-interacting protein Friend Of GATA-1 (FOG-1) is essential for the proper transcriptional activation and repression of numerous GATA-1 target genes. Although FOG-1-independent activation by GATA-1 has been described, all known examples of GATA-1-mediated repression are FOG-1 dependent. In the GATA-1-null G1E cell line, estrogen receptor ligand binding domain (ER) chimeras of either wild-type GATA-1 or a FOG-1-binding defective mutant of GATA-1 repressed several genes similarly upon activation with beta-estradiol. Repression also occurred in a FOG-1-null cell line expressing ER-GATA-1 and during ex vivo erythropoiesis. At the Lyl1 and Rgs18 loci, we found highly restricted occupancy by GATA-1 and GATA 2, indicating that these genes are direct targets of GATA factor regulation. The identification of genes repressed by GATA-1 independent of FOG-1 defines a novel mode of GATA-1-mediated transcriptional regulation. PMID- 17339419 TI - Proteomic patterns predict acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. AB - Acute graft-versus-host disease (aGvHD) contributes significantly to morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo HSCT). Diagnosis of GvHD is mainly based on clinical features and tissue biopsies. A noninvasive, unbiased laboratory test for GvHD diagnosis does not exist. Here we describe the application of capillary electrophoresis coupled online with mass spectrometry (CE-MS) to 13 samples from 10 patients with aGvHD of grade II or more and 50 control samples from 23 patients without GvHD. About 170 GvHD-specific polypeptides were detected and a tentatively aGvHD-specific model consisting of 31 polypeptides was chosen, allowing correct classification of 13 of 13 (sensitivity 100.0% [95% confidence interval {CI} 75.1 to 100.0]) aGvHD samples and 49 of 50 (specificity 98.0% [95% CI 89.3 to 99.7]) control samples of the training set. The subsequent blinded evaluation of 599 samples enabled diagnosis of aGvHD greater than grade II, even prior to clinical diagnosis, with a sensitivity of 83.1% (95% CI 73.1 to 87.9) and a specificity of 75.6% (95% CI 71.6 to 79.4). Thus, high-resolution proteome analysis represents an unbiased laboratory-based screening method, enabling diagnosis, and possibly enabling preemptive therapy. PMID- 17339420 TI - TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC). AB - Currently availabel staging systems for non-Hodgkin lymphomas are not useful for clinical staging classification of most primary cutaneous lymphomas. The tumor, node, metastases (TNM) system used for mycosis fungoides (MF) and Sezary syndrome (SS) is not appropriate for other primary cutaneous lymphomas. A usable, unified staging system would improve the communication about the state of disease, selection of appropriate management, standardization of enrollment/response criteria in clinical trials, and collection/analysis of prospective survival data. Toward this goal, during the recent meetings of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC), the representatives have established a consensus proposal of a TNM classification system applicable for all primary cutaneous lymphomas other than MF and SS. Due to the clinical and pathologic heterogeneity of the cutaneous lymphomas, the currently proposed TNM system is meant to be primarily an anatomic documentation of disease extent and not to be used as a prognostic guide. PMID- 17339421 TI - TLR3 ligand stimulates fully functional memory CD8+ T cells in the absence of CD4+ T-cell help. AB - We investigated whether Toll-like receptor ligands (TLR-Ls) can bypass the requirement for CD4(+) T-cell help in the induction of fully efficient memory CD8(+) T cells (cytotoxic T lymphocytes [CTLs]). "Helpless" CTLs were induced by a synthetic CD8(+) T-cell epitope administered with TLR3-L and TLR9-L, but not with TLR2/6-L, TLR4-L, or TLR7-L. The up-regulation of MHC-I and costimulatory molecules by dendritic cells following TLR stimulation was not sufficient for the priming of "helpless" CTLs, which depended essentially on the induction of a strong IFN-alpha/beta response. The "helpless" CTLs induced by TLR-Ls differentiated into fully functional memory CTLs able to proliferate as well as their "helped" counterparts upon challenge, in the absence of CD4(+) T-cell help. PMID- 17339422 TI - A novel proteoliposomal vaccine induces antitumor immunity against follicular lymphoma. AB - Clinical studies suggest that treatment with vaccines comprised of idiotype protein may be associated with improved clinical outcome in follicular lymphoma patients. The time-consuming process required to generate patient-specific vaccines is a major limitation, however. Here we report results of a pilot clinical trial with a novel autologous, tumor-derived proteoliposome vaccine formulation that could be rapidly produced within a single day. Vaccination was safe, induced autologous tumor-specific type 1 cytokine responses in 5 out of 10 follicular lymphoma patients, and was associated with induction of a sustained complete response in one patient. Other patients had large tumor burdens and progressed after a median duration of 8 months. These results suggest that further testing of this vaccine formulation, particularly in the setting of minimal disease, is warranted. Furthermore, the proteoliposome formulation may provide a model for vaccine development for other human cancers, for which tumor associated antigens need not be defined. PMID- 17339424 TI - The DC-SIGN-related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells. AB - Liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin [CLEC4G]) is a C-type lectin encoded within the liver/lymph node-specific intercellular adhesion molecule-3-grabbing nonintegrin (L-SIGN)/dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)/CD23 gene cluster. LSECtin expression has been previously described as restricted to sinusoidal endothelial cells of the liver and lymph node. We now report LSECtin expression in human peripheral blood and thymic dendritic cells isolated ex vivo. LSECtin is also detected in monocyte-derived macrophages and dendritic cells at the RNA and protein level. In vitro, interleukin-4 (IL-4) induces the expression of 3 LSECtin alternatively spliced isoforms, including a potentially soluble form (Delta 2 isoform) and a shorter version of the prototypic molecule (Delta3/4 isoform). LSECtin functions as a pathogen receptor, because its expression confers Ebola virus-binding capacity to leukemic cells. Sugar-binding studies indicate that LSECtin specifically recognizes N-acetyl-glucosamine, whereas no LSECtin binding to Mannan- or N-acetyl-galactosamine-containing matrices are observed. Antibody or ligand-mediated engagement triggers a rapid internalization of LSECtin,which is dependent on tyrosine and diglutamic-containing motifs within the cytoplasmic tail. Therefore, LSECtin is a pathogen-associated molecular pattern receptor in human myeloid cells. In addition, our results suggest that LSECtin participates in antigen uptake and internalization, and might be a suitable target molecule in vaccination strategies. PMID- 17339423 TI - Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myeloma. AB - The heparan sulfate (HS) proteoglycan, syndecan-1, plays a major role in multiple myeloma (MM) by concentrating heparin-binding growth factors on the surface of MM cells (MMCs). Using Affymetrix microarrays and real-time reverse transcriptase polymerase chain reaction (RT-PCR), we show that the gene encoding heparanase (HPSE), an enzyme that cleaves HS chains, is expressed by 11 of 19 myeloma cell lines (HMCLs). In HSPE(pos) HMCLs, syndecan-1 gene expression and production of soluble syndecan-1, unlike expression of membrane syndecan-1, were significantly increased. Knockdown of HPSE by siRNA resulted in a decrease of syndecan-1 gene expression and soluble syndecan-1 production without affecting membrane syndecan 1 expression. Thus, HPSE influences expression and shedding of syndecan-1. Contrary to HMCLs, HPSE is expressed in only 4 of 39 primary MMC samples, whereas it is expressed in 36 of 39 bone marrow (BM) microenvironment samples. In the latter, HPSE is expressed at a median level in polymorphonuclear cells and T cells; it is highly expressed in monocytes and osteoclasts. Affymetrix data were validated at the protein level, both on HMCLs and patient samples. We report for the first time that a gene's expression mainly in the BM environment (ie, HSPE) is associated with a shorter event-free survival of patients with newly diagnosed myeloma treated with high-dose chemotherapy and stem cell transplantation. Our study suggests that clinical inhibitors of HPSE could be beneficial for patients with MM. PMID- 17339425 TI - Resistance to TGF-beta 1 correlates with aberrant expression of TGF-beta receptor II in human B-cell lymphoma cell lines. AB - Resistance to transforming growth factor (TGF)-beta1-mediated growth suppression in tumor cells is often associated with the functional loss of TGF-beta receptors. Here we describe two B-cell lymphoma cell lines (DB and RL) that differ in their sensitivity to TGF-beta1-mediated growth suppression. The TGF beta1-resistant cell line DB lacked functional TGF-beta receptor II (T beta RII) in contrast to the TGF-beta-responsive cell line RL, whereas both cell lines had comparable levels of receptor I (T beta RI). Lack of functional T beta RII was correlated with the lack of TGF-beta1-induced nuclear translocation of phospho Smad3 and phospho-Smad2, the lack of nuclear expression of p21(Cip1/WAF1), and the down-regulation of c-Myc in DB cells. Transfection of wild-type, but not a C terminal-truncated, form of T beta RII rendered the DB cell line responsive to TGF-beta1-mediated growth suppression. Analysis of the T beta RII gene in DB cells revealed the absence of T beta RII message, which was reversed upon 5' azacytidine treatment, indicating that the promoter methylation might be the cause of gene silencing. Promoter analysis revealed CpG methylations at -25 and 140 that correlated with the gene silencing. These data suggest that promoter methylation plays an important role in T beta RII gene silencing and subsequent development of a TGF-beta1-resistant phenotype by some B-cell lymphoma cells. PMID- 17339426 TI - Maternal acceptance of the fetus: true human tolerance. AB - Induction and maintenance of immunologic tolerance in humans remains a desirable but elusive goal. Therefore, understanding the physiologic mechanisms of regulation of immune responses is highly clinically relevant for immune-mediated diseases (e.g., autoimmunity and asthma/allergy) and for cell and organ transplantation. Acceptance of the fetus, which expresses paternally inherited alloantigens, by the mother during pregnancy is a unique example of how the immune system reshapes a destructive alloimmune response to a state of tolerance. Understanding the complex mechanisms of fetomaternal tolerance has important implications for developing novel strategies to induce immunologic tolerance in humans in general and for prevention of spontaneous abortion in at-risk populations in particular. PMID- 17339427 TI - Cutting Edge: Acute and chronic exposure of immature B cells to antigen leads to impaired homing and SHIP1-dependent reduction in stromal cell-derived factor-1 responsiveness. AB - An encounter of B cells with cognate self Ags in the periphery can lead to anergy, a condition characterized by altered anatomical localization, shortened life span, and refractility to Ag stimulation. We recently reported that an immature B cell encounter with cognate self-Ag in the bone marrow can also lead to anergy. In this study we show that anergic as well as acutely Ag-stimulated immature B cells are defective in stromal cell-derived factor-1 (SDF-1)-induced calcium mobilization and migration and do not localize to bone marrow following adoptive transfer. This hyporesponsiveness does not involve CXCR4 modulation. However, BCR signal-mediated hyporesponsiveness to SDF-1 is associated with phosphorylation of the 5-inositol phosphatase SHIP1 and requires SHIP1 expression. Therefore, an encounter with cognate Ag may, by preventing SDF-1 induced phosphatidylinositol 3,4,5-triphosphate accumulation, trigger premature emigration of immature B cells from bone marrow. PMID- 17339428 TI - Cutting Edge: Chemokine receptor CCR4 is necessary for antigen-driven cutaneous accumulation of CD4 T cells under physiological conditions. AB - Dual expression of chemokine receptor CCR4 and E-selectin ligand is characteristic of skin-tropic CD4 T cells from blood, lymphoid organs, and the skin itself. A strong and specific correlation exists among CCR4, its ligand CCL17/TARC, and the cutaneous lymphocyte-homing process. Nevertheless, whether CCR4 function is required for skin-specific trafficking remains an open question, which we address in this study. We developed an Ag-specific, TCR-transgenic, murine CD4 T cell adoptive transfer model that induces a mixed Th1 and Th17 cutaneous response. Within the hosts, both CCR4(+/+) and CCR4(-/-) donor CD4 T cells contribute equally well to the circulating E-selectin ligand(+) pool in response to Ag. However, only CCR4(+/+) donor cells accumulate efficiently within the skin. CCR4(-/-) cells home normally to the peritoneum, showing that they do not have a general defect in lymphocyte trafficking. We conclude that under physiological conditions, CCR4 is a nonredundant, necessary component of skin specific lymphocyte trafficking. PMID- 17339429 TI - Cutting Edge: Antibody-mediated TLR7-dependent recognition of viral RNA. AB - TLR7 recognizes the genome of ssRNA viruses such as Coxsackievirus B. Because TLR7 is expressed in intracellular compartments, viral RNA must be internalized before its recognition by TLR7. In this study, we define plasmacytoid dendritic cells (pDC) as peripheral blood mononuclear immune cells that respond to Coxsackievirus. pDC activation by Coxsackievirus B requires the presence of specific antiviral Abs. We show that Fc receptors mediate the recognition of virus-Ab complexes and that TLR7 is required for human and murine pDC production of cytokines. These data define a pathway by which intracellular TLR7 senses viral RNA and indicate a role for TLRs in association with Abs in sustaining virus-specific responses. PMID- 17339430 TI - Cutting Edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I dependent antiviral responses in human lung epithelial cells. AB - Influenza A virus (IAV) triggers a contagious acute respiratory disease that causes considerable mortality annually. Recently, we established a role for the pattern-recognition TLR3 in the response of lung epithelial cells to IAV-derived dsRNA. However, additional nucleic acid-recognition proteins have lately been implicated as key viral sensors, including the RNA helicases retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene (MDA)-5. In this study, we investigated the respective role of TLR3 vs RIG-I/MDA-5 signaling in human respiratory epithelial cells infected by IAV using BEAS-2B cells transfected with vectors encoding either a dominant-negative form of TLR3 or of mitochondrial antiviral signaling protein (MAVS; a signaling intermediate of RIG I and MDA-5), or with plasmids overexpressing functional RIG-I or MDA-5. We demonstrate that the sensing of IAV by TLR3 primarily regulates a proinflammatory response, whereas RIG-I (but not MDA-5) mediates both a type I IFN-dependent antiviral signaling and a proinflammatory response. PMID- 17339431 TI - Cutting Edge: Proinflammatory and Th2 cytokines synergize to induce thymic stromal lymphopoietin production by human skin keratinocytes. AB - Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that strongly activates dendritic cells (DC) and can initiate allergic inflammation. The factors inducing the production of human TSLP are not known. In this study, we show that proinflammatory (TNF-alpha or IL-1alpha) and Th2 (IL-4 or IL-13) cytokines synergized to induce the production of TSLP in human skin explants. TSLP production in situ was restricted to epidermal keratinocytes of the suprabasal layer. TSLP production could not be inhibited by factors regulating Th2 inflammation, such as IL-10, TGF-beta, or IFN-gamma. Cytokine-treated skin culture supernatants induced the maturation of blood CD11c(+) DC in a TSLP dependent manner. Our data provide the first evidence of TSLP induction and subsequent DC activation in human skin. Blocking TSLP-inducing cytokines could represent a novel strategy for the treatment of allergic diseases. PMID- 17339432 TI - The Fas/Fas ligand system inhibits differentiation of murine osteoblasts but has a limited role in osteoblast and osteoclast apoptosis. AB - Apoptosis through Fas/Fas ligand (FasL) is an important regulator of immune system homeostasis but its role in bone homeostasis is elusive. We systematically analyzed: 1) the expression of Fas/FasL during osteoblastogenesis and osteoclastogenesis in vitro, 2) the effect of FasL on apoptosis and osteoblastic/osteoclastic differentiation, and 3) osteoblastogenesis and osteoclastogenesis in mice deficient in Fas or FasL. The expression of Fas increased with osteoblastic differentiation. Addition of FasL weakly increased the proportion of apoptotic cells in both osteoclastogenic and osteoblastogenic cultures. In a CFU assay, FasL decreased the proportion of osteoblast colonies but did not affect the total number of colonies, indicating specific inhibitory effect of Fas/FasL on osteoblastic differentiation. The effect depended on the activation of caspase 8 and was specific, as addition of FasL to osteoblastogenic cultures significantly decreased gene expression for runt-related transcription factor 2 (Runx2) required for osteoblastic differentiation. Bone marrow from mice without functional Fas or FasL had similar osteoclastogenic potential as bone marrow from wild-type mice, but generated more osteoblast colonies ex vivo. These colonies had increased expression of the osteoblast genes Runx2, osteopontin, alkaline phosphatase, bone sialoprotein, osteocalcin, and osteoprotegerin. Our results indicate that Fas/FasL system primarily controls osteoblastic differentiation by inhibiting progenitor differentiation and not by inducing apoptosis. During osteoclastogenesis, the Fas/FasL system may have a limited effect on osteoclast progenitor apoptosis. The study suggests that Fas/FasL system plays a key role in osteoblastic differentiation and provides novel insight into the interactions between the immune system and bone. PMID- 17339433 TI - Serpin-6 expression protects embryonic stem cells from lysis by antigen-specific CTL. AB - The immune response to embryonic stem (ES) cells is still poorly understood. In this study, we addressed the adaptive cellular immune response to undifferentiated and differentiated ES cells infected with lymphocytic choriomeningitis virus (LCMV), a vertically transmitted pathogen in mice and humans. In contrast to the prevailing view, we found that undifferentiated and differentiated murine ES cells express MHC class I molecules, although at low levels. When cocultured with LCMV-infected ES cells, syngeneic but not allogeneic LCMV-specific CTL secrete IFN-gamma. Strikingly, LCMV-specific CTL do not efficiently kill LCMV-infected ES cells. ES cells showed high-level expression of the serine protease inhibitor 6, an endogenous inhibitor of the CTL-derived cytotoxic effector molecule granzyme B. Down-regulation of serpin-6 by RNA interference sensitized ES cells for CTL-induced cell death. The results of this study suggest that LCMV-infected murine ES cells present viral Ags and are recognized by LCMV-specific CTL in a MHC class I-restricted manner, yet resist CTL-mediated lysis through high-level expression of serine protease inhibitor 6. PMID- 17339434 TI - Treatment-enhanced CD4+Foxp3+ glucocorticoid-induced TNF receptor family related high regulatory tumor-infiltrating T cells limit the effectiveness of cytokine based immunotherapy. AB - Regulatory T cells can suppress activated CD4+ and CD8+ T effector cells and may serve as an impediment to spontaneous or therapeutic type 1 antitumor immunity. In a previous study, we observed minimal therapeutic impact, but significantly enhanced T cell cross-priming and lesional infiltration of tumor-reactive CD8+ T cells into established CMS4 sarcomas after combined treatment of BALB/c mice with rFLt3 ligand (rFL) and recombinant GM-CSF (rGM-CSF). In this study, we show that this cytokine regimen also results in the profound enhancement of CD4+ tumor infiltrating lymphocytes (TIL) expressing FoxP3, IL-10, and TGF-beta mRNA, with 50 or 90% of CD4+ TIL coexpressing the CD25 and glucocorticoid-induced TNFR family related molecules, respectively. Intracellular staining for Foxp3 protein revealed that combined treatment with rFL plus rGM-CSF results in a significant increase in CD4+Foxp3+ T cells in the spleen of both control and tumor-bearing mice, and that nearly half of CD4+ TIL expressed this marker. In addition, CD4+ TIL cells were of an activated/memory (ICOS(high)CD62L(low)CD45RB(low)) phenotype and were capable of suppressing allospecific T cell proliferation and IFN-gamma production from (in vivo cross-primed) anti-CMS4 CD8+ T cells in vitro, via a mechanism at least partially dependent on IL-10 and TGF-beta. Importantly, in vivo depletion of CD4+ T cells resulted in the ability of previously ineffective, rFL plus rGM-CSF therapy-induced CD8+ T cells to now mediate tumor regression. PMID- 17339435 TI - Analysis of TCRalphabeta combinations used by simian immunodeficiency virus specific CD8+ T cells in rhesus monkeys: implications for CTL immunodominance. AB - Immunodominance is a common feature of Ag-specific CTL responses to infection or vaccines. Understanding the basis of immunodominance is crucial to understanding cellular immunity and viral evasion mechanisms and will provide a rational approach for improving HIV vaccine design. This study was performed comparing CTLs specific for the SIV Gag p11C (dominant) and SIV Pol p68A (subdominant) epitopes that are consistently generated in Mamu-A*01(+) rhesus monkeys exposed to SIV proteins. Additionally, vaccinated monkeys were used to prevent any issues of antigenic variation or dynamic changes in CTL responses by continuous Ag exposure. Analysis of the TCR repertoire revealed the usage of higher numbers of TCR clones by the dominant p11C-specific CTL population. Preferential usage of specific TCRs and the in vitro functional TCR-alpha- and -beta-chain-pairing assay suggests that every peptide/MHC complex may only be recognized by a limited number of unique combinations of alpha- and beta-chain pairs. The wider array of TCR clones used by the dominant p11C-specific CTL population might be explained by the higher probability of generating those specific TCR chain pairs. Our data suggest that Ag-specific naive T cell precursor frequency may be predetermined and that this process dictates immunodominance of SIV-specific CD8(+) T cell responses. These findings will aid in understanding immunodominance and designing new approaches to modulate CTL responses. PMID- 17339436 TI - The activating NKG2D ligand MHC class I-related chain A transfers from target cells to NK cells in a manner that allows functional consequences. AB - Recently, it has become apparent that surface proteins commonly transfer between immune cells in contact. Inhibitory receptors and ligands exchange between cells during NK cell surveillance and we report here that NK cells also acquire activating ligands from target cells. Specifically, the stress-inducible activating ligand for NKG2D, MHC class I-related chain A (MICA), transferred to NK cells upon conjugation with MICA-expressing target cells. Acquisition of MICA from target cells was dependent on cell contact and occurred after accumulation of MICA at the immunological synapse. Moreover, transfer of MICA was facilitated by specific molecular recognition via NKG2D and augmented by Src kinase signaling. Importantly, MICA associated with its new host NK cell membrane in an orientation that allowed engagement with NKG2D in trans and indeed could down regulate NKG2D in subsequent homotypic interactions with other NK cells. MICA captured from target cells could subsequently transfer between NK cells and, more importantly, NK cell degranulation was triggered in such NK cell-NK cell interactions. Thus, NK cells can influence other NK cells with proteins acquired from target cells and our data specifically suggest that NK cells could lyse other NK cells upon recognition of activating ligands acquired from target cells. This mechanism could constitute an important function for immunoregulation of NK cell activity. PMID- 17339437 TI - Targeting of the transcription factor STAT4 by antisense phosphorothioate oligonucleotides suppresses collagen-induced arthritis. AB - The transcription factor STAT4 mediates signals of various proinflammatory cytokines, such as IL-12, IL-15, and IL-23, that initiate and stabilize Th1 cytokine production. Although Th1 cytokine production has been suggested to play a major pathogenic role in rheumatoid arthritis, the role of STAT4 in this disease is poorly understood. In this study, we demonstrate a key functional role of STAT4 in murine collagen-induced arthritis (CIA). In initial studies we found that STAT4 expression is strongly induced in CD4(+) T cells and to a lesser extent in CD11b(+) APCs during CIA. To analyze the role of STAT4 for arthritis manifestation, we next investigated the outcome of interfering with STAT4 gene expression in CIA by using STAT4-deficient mice. Interestingly, STAT4-deficient mice developed significantly less severe arthritis than wild-type control mice and the T cells from such mice produced less IL-6, TNF, and IL-17. In addition, the targeting of STAT4 expression by a specific antisense phosphorothioate oligonucleotide directed at the translation start site suppressed STAT4 levels and signs of CIA even when applied during the onset of disease manifestation. These data suggest a key regulatory role of STAT4 in the pathogenesis and manifestation of murine collagen-induced arthritis. Furthermore, the targeting of STAT4 emerges as a novel approach to therapy for chronic arthritis. PMID- 17339438 TI - Migration of CD4 T cells and dendritic cells toward sphingosine 1-phosphate (S1P) is mediated by different receptor subtypes: S1P regulates the functions of murine mature dendritic cells via S1P receptor type 3. AB - Dendritic cells (DCs) and lymphocytes are known to show a migratory response to the phospholipid mediator, sphingosine 1-phosphate (S1P). However, it is unclear whether the same S1P receptor subtype mediates the migration of lymphocytes and DCs toward S1P. In this study, we investigated the involvement of S1P receptor subtypes in S1P-induced migration of CD4 T cells and bone marrow-derived DCs in mice. A potent S1P receptor agonist, the (S)-enantiomer of FTY720-phosphate [(S) FTY720-P], at 0.1 nM or higher and a selective S1P receptor type 1 (S1P(1)) agonist, SEW2871, at 0.1 muM or higher induced a dose-dependent down-regulation of S1P(1). The pretreatment with these compounds resulted in a significant inhibition of mouse CD4 T cell migration toward S1P. Thus, it is revealed that CD4 T cell migration toward S1P is highly dependent on S1P(1). Mature DCs, when compared with CD4 T cells or immature DCs, expressed a relatively higher level of S1P(3) mRNA. S1P at 10-1000 nM induced a marked migration and significantly enhanced the endocytosis of FITC-dextran in mature but not immature DCs. Pretreatment with (S)-FTY720-P at 0.1 microM or higher resulted in a significant inhibition of S1P-induced migration and endocytosis in mature DCs, whereas SEW2871 up to 100 microM did not show any clear effect. Moreover, we found that S1P-induced migration and endocytosis were at an extremely low level in mature DCs prepared from S1P(3)-knockout mice. These results indicate that S1P regulates migration and endocytosis of murine mature DCs via S1P(3) but not S1P(1). PMID- 17339439 TI - B cell regulation of CD4+CD25+ T regulatory cells and IL-10 via B7 is essential for recovery from experimental autoimmune encephalomyelitis. AB - CD4(+)CD25(+) T regulatory (Treg) cells expressing the Foxp3 transcription factor have been shown to be present in the CNS during the autoimmune disease experimental autoimmune encephalomyelitis (EAE) and can inhibit EAE clinical disease by an IL-10-dependent mechanism. In addition, IL-10 expression in the CNS late in the EAE disease course has been attributed to recovery. However, it is not known how Treg cells and IL-10 expressions are regulated during EAE. We have previously shown a requirement for B cells in recovery from EAE and here investigated whether this was due to a deficiency in Treg cells and IL-10 in the CNS. We found that B cell deficiency resulted in a delay in the emergence of Foxp3-expressing Treg cells and IL-10 in the CNS during EAE, but not in the periphery. Reconstitution with wild-type B cells resulted in disease recovery and normalized IL-10 and Foxp3 expression. However, reconstitution with B7-deficient B cells did not. Furthermore, we show that IL-10 and Foxp3 expression is enhanced in CNS nonencephalitogenic T cells. These data suggest a novel mechanism whereby B cells regulate CD4(+)CD25(+) Treg cells via B7 and subsequently enter the CNS and suppress autoimmune inflammation, mediating recovery. PMID- 17339440 TI - Temporal dissection of T-bet functions. AB - T-bet is a transcription factor of the T-box family that regulates the expression of numerous immune system-associated genes. T-bet directs the acquisition of the Th1-associated genetic program in differentiating CD4(+) lymphocytes. It also influences the development of NK and NKT cells through its regulation of the IL 2/IL-15Rbeta-chain (CD122) and the trafficking of these lymphocytes through CxCR3. The temporal requirements of T-bet activity for the production of IFN gamma and the regulation of CD122 and CxCR3 expression remain undefined. We produced an ectopically controllable form of T-bet by fusing its C-terminal domain with a mutated ligand-binding domain of human estrogen receptor alpha. By temporally controlling the expression of T-bet-estrogen receptor alpha by the addition or removal of 4-hydroxytamoxifen (4-HT), we show that IFN-gamma, CD122, and CxCR3 are direct gene targets of T-bet whose expression are acutely regulated by T-bet activity. PMID- 17339441 TI - TLR ligands act directly upon T cells to restore proliferation in the absence of protein kinase C-theta signaling and promote autoimmune myocarditis. AB - The serine/threonine kinase, protein kinase C-theta (PKC-theta), plays a central role in the activation and differentiation of Th2 cells while being redundant in CD4+ and CD8+ antiviral responses. Recent evidence indicates that PKC-theta may however be required for some T cell-driven autoimmune responses. We have investigated the role of PKC-theta in the induction of autoimmune myocarditis induced by either Coxsackie B3 virus infection or immunization with alpha myosin/CFA (experimental autoimmune myocarditis (EAM)). PKC-theta-deficient mice did not develop EAM as shown by impaired inflammatory cell infiltration into the heart, reduced CD4+ T cell IL-17 production, and the absence of a myosin-specific Ab response. Comparatively, PKC-theta was not essential for both early and late phase Coxsackie virus-induced myocarditis. We sought to find alternate pathways of immune stimulation that might reconcile the differential requirements for PKC theta in these two disease models. We found systemic administration of the TLR ligand CpG restored EAM in PKC-theta-deficient mice. CpG could act directly upon TLR9-expressing T cells to restore proliferation and up-regulation of Bcl-x(L), but exogenous IL-6 and TGF-beta was required for Th17 cell differentiation. Taken together, these results indicate that TLR-mediated activation of T cells can directly overcome the requirement for PKC-theta signaling and, combined with the dendritic cell-derived cytokine milieu, can promote the development of autoimmunity. PMID- 17339442 TI - Regulatory T cells are resistant to apoptosis via TCR but not P2X7. AB - Regulatory T cells (Tregs) are relatively autoreactive yet, paradoxically, have been found to display normal sensitivity to thymic deletion. The relationship between self-avidity, apoptosis, and the selection of Tregs therefore remains unclear. We show that thymic Tregs develop efficiently, even at low self-avidity, and are moderately resistant to apoptosis in comparison to conventional thymocytes. Consistent with this, although conventional self-reactive T cell populations undergo chronic peripheral deletion, self-reactive Tregs are largely spared removal. Similarly, the distribution of Tregs among peripheral CD4(+) cells exhibits a linear inverse relationship with CD45RB expression, indicating relative apoptosis resistance of Tregs in chronic responses to environmental Ags. We also show that appropriate controls for CD45RB levels are important for comparisons of Treg and conventional T cell activity. When thus controlled, and contrary to previous reports, Tregs exhibit normal sensitivity to cell death through TCR-independent stimuli, such as the purinergic receptor, P2X(7). Finally, although absence of CD45 in gene-targeted mice results in profound T cell hyporesponsiveness, there is little or no effect on thymic Treg frequency. In summary, the data support a model in which signal strength plays little part in Treg lineage specification, though moderate resistance of self-reactive Tregs to apoptosis may result in progressive biasing of peripheral Treg TCRs toward autoreactivity in comparison to those of conventional T cells. PMID- 17339443 TI - Differential survival of cytotoxic T cells and memory cell precursors. AB - It is widely assumed that the development of memory CD8 T cells requires the escape of CTLs from programmed cell death. We show in this study that although serine protease inhibitor 6 (Spi6) is required to protect clonal bursts of CTLs from granzyme B-induced programmed cell death, it is not required for the development of memory cells. This conclusion is reached because memory cell precursors down-regulate both Spi6 and granzyme B, unlike CTLs, and they do not require Spi6 for survival. These findings suggest that memory CD8 T cells are derived from progenitors that are refractory to self-inflicted damage, rather than derived from fully differentiated CTLs. PMID- 17339444 TI - Interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virus mac251-infected macaques. AB - The loss of CD4(+) T cells and the impairment of CD8(+) T cell function in HIV infection suggest that pharmacological treatment with IL-7 and IL-15, cytokines that increase the homeostatic proliferation of T cells and improve effector function, may be beneficial. However, these cytokines could also have a detrimental effect in HIV-1-infected individuals, because both cytokines increase HIV replication in vitro. We assessed the impact of IL-7 and IL-15 treatment on viral replication and the immunogenicity of live poxvirus vaccines in SIV(mac251) infected macaques (Macaca mulatta). Neither cytokine augmented the frequency of vaccine-expanded CD4(+) or CD8(+) memory T cells, clonal recruitment to the SIV specific CD8(+) T cell pool, or CD8(+) T cell function. Vaccination alone transiently decreased the viral set point following antiretroviral therapy suspension. IL-15 induced massive proliferation of CD4(+) effector T cells and abrogated the ability of vaccination to decrease set point viremia. In contrast, IL-7 neither augmented nor decreased the vaccine effect and was associated with a decrease in TGF-beta expression. These results underscore the importance of testing immunomodulatory approaches in vivo to assess potential risks and benefits for HIV-1-infected individuals. PMID- 17339445 TI - Type I IFN signaling on both B and CD4 T cells is required for protective antibody response to adenovirus. AB - Recombinant adenoviruses have been used as vehicles for gene therapy as well as vaccination against infectious diseases and cancer. Efficient activation of host B cell response to adenoviral vectors that leads to the generation of protective, neutralizing Ab, represents a major barrier for gene therapy, but an attractive feature for vaccine development. What regulate(s) potent B cell response to adenoviral vectors remains incompletely defined. In this study, we showed that type I IFNs induced upon adenoviral infection are critical for multiple stages of adaptive B cell response to adenovirus including early B cell activation, germinal center formation, Ig isotype switching as well as plasma cell differentiation. We further demonstrated that although type I IFN signaling on dendritic cells was important for the production of virus-specific IgM, the generation of protective neutralizing Ab critically depended on type I IFN signaling on both CD4 T and B cells. The results may suggest potential strategies for improving adenovirus-mediated gene therapy in vivo and/or the design of effective vaccines for cancer and infectious diseases. PMID- 17339446 TI - Identification of adiponectin as a novel hemopoietic stem cell growth factor. AB - The hemopoietic microenvironment consists of a diverse repertoire of cells capable of providing signals that influence hemopoietic stem cell function. Although the role of osteoblasts and vascular endothelial cells has recently been characterized, the function of the most abundant cell type in the bone marrow, the adipocyte, is less defined. Given the emergence of a growing number of adipokines, it is possible that these factors may also play a role in regulating hematopoiesis. Here, we investigated the role of adiponectin, a secreted molecule derived from adipocytes, in hemopoietic stem cell (HSC) function. We show that adiponectin is expressed by components of the HSC niche and its receptors AdipoR1 and AdipoR2 are expressed by HSCs. At a functional level, adiponectin influences HSCs by increasing their proliferation, while retaining the cells in a functionally immature state as determined by in vitro and in vivo assays. We also demonstrate that adiponectin signaling is required for optimal HSC proliferation both in vitro and in long term hemopoietic reconstitution in vivo. Finally we show that adiponectin stimulation activates p38 MAPK, and that inhibition of this pathway abrogates adiponectin's proliferative effect on HSCs. These studies collectively identify adiponectin as a novel regulator of HSC function and suggest that it acts through a p38 dependent pathway. PMID- 17339447 TI - Accelerated Notch-dependent degradation of E47 proteins in aged B cell precursors is associated with increased ERK MAPK activation. AB - The transcriptional regulator E47, encoded by the E2A gene, is crucial to B lymphopoiesis. In BALB/c senescent mice (approximately 2 years old), the incidence of E47-expressing pro-B cells in vivo and E47 protein steady state levels in B cell precursors in vitro were reduced. Poor expression of E47 protein was a consequence of accelerated proteasome-mediated turnover and was associated with heightened ubiquitin modification of E2A-encoded proteins in aged B cell precursors. Both MAPK and Notch activity have been previously associated with E2A encoded protein stability in lymphocytes. Aged B cell precursors exhibited heightened levels of MAPK activity reflected in increased levels of phospho-ERK proteins. Phosphorylation of E2A-encoded proteins was also increased in aged B cell precursors and pharmacologic inhibition of MEK-1 resulted in a partial restoration of their E47 protein. Both Notch proteins and their Delta-like ligands were detected comparably in young and aged B cell precursors. Either inhibition of Notch activation via gamma-secretase or Ab blockade of Notch-Delta like ligand interactions partially restored E47 expression in aged B cell precursors. We hypothesize that increased MAPK activity promotes phosphorylation of E2A-encoded protein in aged B cell precursors. Subsequently, E2A-encoded proteins undergo ubiquitination and accelerated degradation in a Notch-dependent process. The dysregulation of E2A-encoded protein expression may contribute to the reductions seen in early B lymphopoiesis during murine senescence. PMID- 17339448 TI - Kinetic proofreading of ligand-FcepsilonRI interactions may persist beyond LAT phosphorylation. AB - Cells may discriminate among ligands with different dwell times for receptor binding through a mechanism called kinetic proofreading in which the formation of an activated receptor complex requires a progression of events that is aborted if the ligand dissociates before completion. This mechanism explains how, at equivalent levels of receptor occupancy, a rapidly dissociating ligand can be less effective than a more slowly dissociating analog at generating distal cellular responses. Simple mathematical models predict that kinetic proofreading is limited to the initial complex; once the signal passes to second messengers, the dwell time no longer regulates the signal. This suggests that an assay for kinetic proofreading might be used to determine which activation events occur within the initial signaling complex. In signaling through the high affinity IgE receptor FcepsilonRI, the transmembrane adaptor called linker for activation of T cells (LAT) is thought to nucleate a distinct secondary complex. Experiments in which the concentrations of two ligands with different dwell times are adjusted to equalize the level of LAT phosphorylation in rat basophilic leukemia 2H3 cells show that Erk2 phosphorylation, intracellular Ca(2+), and degranulation exhibit kinetic proofreading downstream of LAT phosphorylation. These results suggest that ligand-bound FcepsilonRI and LAT form a complex that is required for effective signal transmission. PMID- 17339449 TI - Increased expression of leukocyte Ig-like receptor-1 and activating role of UL18 in the response to cytomegalovirus infection. AB - NK and T cells are important for combating CMV infection. Some NK and T cells express leukocyte Ig-like receptor-1 (LIR-1), an inhibitory receptor recognizing MHC class I and the CMV-encoded homolog UL18. We previously demonstrated an early increase in LIR-1-expressing blood lymphocytes in lung-transplanted patients later developing CMV disease. We now show that NK and T cells account for the observed LIR-1 augmentation. Coincubation of PBMC from CMV-seropositive donors with virus-infected lung fibroblasts led to a T cell-dependent secretion of IFN gamma, produced mainly by LIR-1(+) T cells and by NK cells. Cytokine production during coculture with fibroblasts infected with virus containing the UL18 gene was augmented compared with the UL18 deletion virus, suggesting a stimulatory role for UL18. However, purified UL18Fc proteins inhibited IFN-gamma production of LIR-1(+) T cells. We propose that cytokine production in the transplant induces NK and T cells to express LIR-1, which may predispose to CMV disease by MHC/LIR-1-mediated suppression. Although the UL18/LIR-1 interaction could inhibit T cell responses, this unlikely plays a role in response to infected cells. Instead, our data point to an activating role for viral UL18 during infection, where indirect intracellular effects cannot be excluded. PMID- 17339450 TI - Discrete T cell populations with specificity for a neo-self-antigen bear distinct imprints of tolerance. AB - Mice expressing the Torpedo acetylcholine receptor alpha-chain as a neo-self-Ag exhibit a reduced frequency of T cells responding to the immunodominant epitope Talpha146-162 indicating a degree of tolerance. We characterized tolerance induction in these animals by analyzing the residual Talpha146-162-responsive T cell population and comparing it to that of nontransgenic littermates. Using CD4(high) sorting, we isolated the vast majority of Ag-reactive T cells from both strains of mice. Quantitative studies of the CD4(high) populations in transgenic mice following immunization with Talpha146-162 revealed a diminished expansion of cells expressing the canonical TCRBV6 but not other TCRBV gene segments when compared with nontransgenic littermates. In addition, CD4(high) cells from transgenic mice were functionally hyporesponsive to Talpha146-162 in terms of proliferation and cytokine secretion regardless of TCRBV gene segment use. TCR sequence analysis of transgenic Vbeta6(+)CD4(high) cells revealed a reduced frequency of cells expressing a conserved motif within the TCRbeta CDR3. Thus, the canonical Talpha146-162 responsive, Vbeta6(+) population demonstrates both quantitative and qualitative deficits that correlate with an altered TCR repertoire whereas the non-Vbeta6 population in transgenic mice exhibits only a reduction in peptide responsiveness, a qualitative defect. These data demonstrate that discrete autoreactive T cell populations with identical peptide/MHC specificity in Torpedo acetylcholine receptor-alpha-transgenic animals bear distinct tolerance imprints. PMID- 17339451 TI - Flt3 ligand expands lymphoid progenitors prior to recovery of thymopoiesis and accelerates T cell reconstitution after bone marrow transplantation. AB - Deficient thymopoiesis and retarded recovery of newly developed CD4(+) T cells is one of the most important determinants of impaired immunocompetence after hemopoietic stem cell transplantation. Here we evaluated whether Fms-like tyrosine kinase 3 (Flt3) ligand (FL) alone or combined with IL-7 affects T cell recovery, thymopoiesis, and lymphoid progenitor expansion following bone marrow transplantation in immunodeficient mice. FL strongly accelerated and enhanced the recovery of peripheral T cells after transplantation of a low number of bone marrow cells. An additive effect on T cell recovery was not observed after coadministration of IL-7. Lineage(-)sca-1(+)c-kit(+)flt3(+) lymphoid progenitor cell numbers were significantly increased in bone marrow of FL-treated mice before recovery of thymopoiesis. Thymocyte differentiation was advanced to more mature stages after FL treatment. Improved T cell recovery resulted in better immunocompetence against a post-bone marrow transplantation murine CMV infection. Collectively, our data suggest that FL promotes T cell recovery by enhanced thymopoiesis and by expansion of lymphoid progenitors. PMID- 17339452 TI - Natural regulation of immunity to minor histocompatibility antigens. AB - MHC-matched hemopoietic stem cell transplantation is commonly used for the treatment of some forms of leukemia. Conditioning regimens before transplant act to reduce the burden of leukemic cells and the graft-vs-leukemia (GvL) effect can eliminate residual disease. The GvL effect results largely from the recognition of minor histocompatibility Ags by donor T cells on recipient tissues. These Ags are generally widely expressed and also provoke graft-vs-host (GvH) disease. Manipulation of immunity to promote GvL while curtailing GvH would greatly improve clinical outcome. To develop strategies that may achieve this, the parameters which control immunity to minor histocompatibility Ags need to be defined. In this study, we have analyzed responses to the mouse HY minor histocompatibility Ag using hemopoietic cell and skin grafts as surrogate GvL and GvH targets, respectively. We show that natural regulation of CD8 T cell responses to HY operates at multiple levels. First, CD4 T cell help is required for primary CD8 responses directed at hemopoietic cells. However, although CD4 T cells of H2(k) mouse strains recognize HY, they provide ineffective help associated with a proportion of recipients developing tolerance. This was further investigated using TCR-transgenic mice which revealed H2(k)-restricted HY specific CD4 T cells are highly susceptible to regulation by CD25(+) regulatory T cells which expand in tolerant recipients. A second level of regulation, operating in the context of skin grafts, involves direct inhibition of CD8 T cell responses by CD94/NKG2 engagement of the nonclassical MHC class I molecule Qa1. PMID- 17339453 TI - IL-12 controls cytotoxicity of a novel subset of self-antigen-specific human CD28+ cytolytic T cells. AB - Activated CD8 T cells develop cytotoxicity against autologous cells bearing foreign Ags and self/tumor Ags. However, self-specific cytolysis needs to be kept under control to avoid overwhelming immunopathology. After peptide vaccination of melanoma patients, we studied molecular and functional properties of T cell subsets specific for the self/tumor Ag Melan-A/MART-1. Ex vivo analysis revealed three Ag-specific effector memory (EM) populations, as follows: CD28-negative EM (EM28(-)) T cells strongly expressing granzyme/perforin, and two EM28(+) subsets, one with high and the other with low level expression of these cytotoxic proteins. For further functional characterization, we generated 117 stable CD8 T cell clones by ex vivo flow cytometry-based sorting of these subsets. All EM28(-) derived clones lysed target cells with high efficacy. In contrast, EM28(+) derived clones were heterogenous, and could be classified in two groups, one with high and the other with low killing capacity, correlating with granzyme/perforin expression. High and low killer phenotypes remained surprisingly stable for several months. However, strongly increased granzyme expression and cytotoxicity were observed after exposure to IL-12. Thus, the data reveal a newly identified subset of CD28(+) conditional killer T cells. Because CD28 can mediate strong costimulatory signals, tight cytotoxicity control, as shown in this study through IL-12, may be particularly important for subsets of T cells expressing CD28. PMID- 17339454 TI - Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. AB - NK cells are effector lymphocytes that can recognize and eliminate virally infected and transformed cells. NK cells express distinct activating receptors, including an ITAM-containing FcR complex that recognizes Ab-coated targets, and the DNAX-activating protein of 10 kDa-containing NKG2D receptor complex that recognizes stress-induced ligands. The regulatory role of specific tyrosine kinases in these pathways is incompletely understood. In this study, we show that, in activated human NK cells, the tyrosine kinase IL-2-inducible T cell kinase (Itk), differentially regulates distinct NK-activating receptors. Enhanced expression of Itk leads to increases in calcium mobilization, granule release, and cytotoxicity upon stimulation of the ITAM-containing FcR, suggesting that Itk positively regulates FcR-initiated cytotoxicity. In contrast, enhanced Itk expression decreases cytotoxicity and granule release downstream of the DNAX activating protein of 10 kDa-containing NKG2D receptor, suggesting that Itk is involved in a pathway of negative regulation of NKG2D-initiated granule-mediated killing. Using a kinase mutant, we show that the catalytic activity of Itk is required for both the positive and negative regulation of these pathways. Complementary experiments where Itk expression was suppressed also showed differential regulation of the two pathways. These findings suggest that Itk plays a complex role in regulating the functions initiated by distinct NK cell activating receptors. Moreover, understanding how these pathways may be differentially regulated has relevance in the setting of autoimmune diseases and antitumor immune responses where NK cells play key regulatory roles. PMID- 17339455 TI - Induction of a Th1 response from Th2-polarized T cells by activated dendritic cells: dependence on TCR:peptide-MHC interaction, ICAM-1, IL-12, and IFN-gamma. AB - Dendritic cells (DC) are important regulators of T cell immunity. The degree of stimulation, the pattern of costimulatory molecules expressed, and the cytokines secreted by DC dictate the nature of the effector and memory cells generated, particularly with respect to their Th1 or Th2 phenotypes. In this study, we demonstrate that the addition of activated DC to spleen cultures containing established Th2-polarized CD4(+) T cells was sufficient to suppress Th2 and induce Th1 cytokines in a recall response, a phenomenon referred to as phenotype reversal. The ability of activated DC to induce phenotype reversal displayed exquisite Ag specificity. The DC activator B7-DC cross-linking Ab (XAb) was >10,000-fold more efficient at inducing phenotype reversal than the TLR agonists CpG-oligodeoxynucleotide and Gardiquimod. Characterization of the mechanisms governing phenotype reversal revealed the requirement for cognate interaction between the TCR:peptide-MHC complex, the expression of the costimulation/adhesion molecule ICAM-1, and secretion of IL-12 and IFN-gamma by the activated DC. The requirement for the costimulation/adhesion molecule SLAM (signaling lymphocytic activation molecule) was found to be quantitative. Thus, activation of DC, particularly by crosslinking B7-DC, can modulate well-established Th2 T cell responses in an Ag-specific manner. Because the regulation of mouse and human DC by B7-DC XAb overlaps in several significant ways, immune modulation with B7-DC XAb is a potential strategy for treating Th2-mediated diseases. PMID- 17339457 TI - IFN regulatory factor-2 regulates macrophage apoptosis through a STAT1/3- and caspase-1-dependent mechanism. AB - IFN regulatory factor (IRF)-2(-/-) mice are significantly more resistant to LPS challenge than wild-type littermates, and this was correlated with increased numbers of apoptotic Kupffer cells. To assess the generality of this observation, and to understand the role of IRF-2 in apoptosis, responses of peritoneal macrophages from IRF-2(+/+) and IRF-2(-/-) mice to apoptotic stimuli, including the fungal metabolite, gliotoxin, were compared. IRF-2(-/-) macrophages exhibited a consistently higher incidence of apoptosis that failed to correlate with caspase-3/7 activity. Using microarray gene expression profiling of liver RNA samples derived from IRF-2(+/+) and IRF-2(-/-) mice treated with saline or LPS, we identified >40 genes that were significantly down-regulated in IRF-2(-/-) mice, including Stat3, which has been reported to regulate apoptosis. Compared with IRF-2(+/+) macrophages, STAT3alpha mRNA was up-regulated constitutively or after gliotoxin treatment of IRF-2(-/-) macrophages, whereas STAT3beta mRNA was down-regulated. Phospho-Y705-STAT3, phospho-S727-STAT1, and phospho-p38 protein levels were also significantly higher in IRF-2(-/-) than control macrophages. Activation of the STAT signaling pathway has been shown to elicit expression of CASP1 and apoptosis. IRF-2(-/-) macrophages exhibited increased basal and gliotoxin-induced caspase-1 mRNA expression and enhanced caspase-1 activity. Pharmacologic inhibition of STAT3 and caspase-1 abolished gliotoxin-induced apoptosis in IRF-2(-/-) macrophages. A novel IFN-stimulated response element, identified within the murine promoter of Casp1, was determined to be functional by EMSA and supershift analysis. Collectively, these data support the hypothesis that IRF-2 acts as a transcriptional repressor of Casp1, and that the absence of IRF-2 renders macrophages more sensitive to apoptotic stimuli in a caspase-1 dependent process. PMID- 17339456 TI - T-independent activation-induced cytidine deaminase expression, class-switch recombination, and antibody production by immature/transitional 1 B cells. AB - Inflammation elicits a splenic lymphopoiesis of unknown physiologic significance but one that juxtaposes developing B cells and exogenous Ag. We show that immature and transitional 1 (immature/T1) B cells constitutively express activation-induced cytidine deaminase and B lymphocyte-induced maturation protein 1 in amounts that support accelerated plasmacytic differentiation and limited class-switch recombination. In vivo, activation of immature/T1 B cells by TLR ligands or bacterial vaccine rapidly induces T1 cells to divide, proliferate, and secrete IgM, IgG, or IgA Ab; in vitro, proliferation and differentiation are substantially enhanced by B cell-activating factor. We propose that inflammation induced extramedullary lymphopoiesis represents a specialized mechanism for innate Ab responses to microbial pathogens. PMID- 17339458 TI - Stimulation of an unfolded protein response impairs MHC class I expression. AB - HFE C282Y is an example of a mutant protein that does not fold correctly, is retained in the endoplasmic reticulum, and was found previously to diminish surface expression of MHC class I (MHC-I). We now show that its expression in 293T cells triggers an unfolded protein response (UPR), as revealed by the increased levels of H chain binding protein, GRP94, and C/EBP homologous protein. Elevated levels of these proteins were also found in HFE C282Y homozygous PBMCs. Following the UPR induction, a decrease in MHC-I cell surface expression was observed. This defect in MHC-I could be mimicked, however, by overexpression of transcriptionally active isoforms of activating transcription factor-6 and X box binding protein-1, which induced the UPR, and reversed in HFE C282Y-expressing cells by using dominant-negative constructs that block UPR signaling. The present results provide evidence to the finding that stimulation of an UPR affects MHC-I expression. PMID- 17339459 TI - CD1-restricted recognition of exogenous and self-lipid antigens by duodenal gammadelta+ T lymphocytes. AB - Gammadelta T cells are present in the mucosal intestinal epithelia and secrete factors necessary to maintain tissue integrity. Ags recognized by these cells are poorly defined, although in mice non-classical MHC class I molecules have been implicated. Since MHC class I-like CD1 receptors are widely expressed at the surface of epithelial and dendritic intestinal cells and have the capacity to present lipid Ags to T cells, we hypothesized that these molecules might present autologous and/or exogenous phospholipids to intestinal gammadelta T lymphocytes. Intraepithelial T lymphocytes from normal human duodenal mucosal biopsies were cloned and exposed to natural and synthetic phospholipids using CD1a-, CD1b-, CD1c- or CD1d-transfected C1R lymphoblastoid or HeLa cell lines as APCs. Their cytolytic properties and regulatory cytokine secretion were also examined. Most clones obtained from duodenal mucosa (up to 70%) were TCRalphabeta+, and either CD4+ or CD8+, whereas 20% were CD4-CD8- (6 clones) or TCRgammadelta+ (12 clones). A relevant percentage (up to 66%) of TCRgammadelta+ but few (<5%) TCRalphabeta+ T cell clones responded to synthetic and/or natural phospholipids presented by CD1 molecules, as measured by both [(3)H]thymidine incorporation and IL-4 release assays. A Th1-like cytolytic and functional activity along with the ability to secrete regulatory cytokines was observed in most phospholipid-specific gammadelta T cell clones. Thus, a substantial percentage of TCRgammadelta+ but few TCRalphabeta+ from human duodenal mucosa recognize exogenous phospholipids in a CD1-restricted fashion. This adaptive response could contribute to mucosal homeostasis, but could also favor the emergence of inflammatory or allergic intestinal diseases. PMID- 17339460 TI - Superantigen presentation by airway smooth muscle to CD4+ T lymphocytes elicits reciprocal proasthmatic changes in airway function. AB - Microbial products serving as superantigens (SAgs) have been implicated in triggering various T cell-mediated chronic inflammatory disorders, including severe asthma. Given earlier evidence demonstrating that airway smooth muscle (ASM) cells express MHC class II molecules, we investigated whether ASM can present SAg to resting CD4(+) T cells, and further examined whether this action reciprocally elicits proasthmatic changes in ASM responsiveness. Coincubation of CD4(+) T cells with human ASM cells pulsed with the SAg, staphylococcal enterotoxin A (SEA), elicited adherence and clustering of class II and CD3 molecules at the ASM/T cell interface, indicative of immunological synapse formation, in association with T cell activation. This ASM/T cell interaction evoked up-regulated mRNA expression and pronounced release of the Th2-type cytokine, IL-13, into the coculture medium, which was MHC class II dependent. Moreover, when administering the conditioned medium from the SEA-stimulated ASM/T cell cocultures to isolated naive rabbit ASM tissues, the latter exhibited proasthmatic-like changes in their constrictor and relaxation responsiveness that were prevented by pretreating the tissues with an anti-IL-13 neutralizing Ab. Collectively, these observations are the first to demonstrate that ASM can present SAg to CD4(+) T cells, and that this MHC class II-mediated cooperative ASM/T cell interaction elicits release of IL-13 that, in turn, evokes proasthmatic changes in ASM constrictor and relaxant responsiveness. Thus, a new immuno-regulatory role for ASM is identified that potentially contributes to the pathogenesis of nonallergic (intrinsic) asthma and, accordingly, may underlie the reported association between microbial SAg exposure, T cell activation, and severe asthma. PMID- 17339461 TI - Capture of target cell membrane components via trogocytosis is triggered by a selected set of surface molecules on T or B cells. AB - Key events of T and B cell biology are regulated through direct interaction with APC or target cells. Trogocytosis is a process whereby CD4(+) T, CD8(+) T, and B cells capture their specific membrane-bound Ag through the acquisition of plasma membrane fragments from their cellular targets. With the aim of investigating whether the ability to trigger trogocytosis was a selective property of Ag receptors, we set up an assay that allowed us to test the ability of many different cell surface molecules to trigger trogocytosis. On the basis of the analysis of a series of surface molecules on CD4(+) T, CD8(+) T, and B cells, we conclude that a set of cell type-specific surface determinants, including but not limited to Ag receptors, do trigger trogocytosis. On T cells, these determinants include components of the TCR/CD3 as well as that of coreceptors and of several costimulatory molecules. On B cells, we identified only the BCR and MHC molecules as potentials triggers of trogocytosis. Remarkably, latrunculin, which prevents actin polymerization, impaired trogocytosis by T cells, but not by B cells. This was true even when the same Abs were used to trigger trogocytosis in T or B cells. Altogether, our results indicate that although trogocytosis is performed by all hemopoietic cells tested thus far, both the receptors and the mechanisms involved can differ depending on the lineage of the cell acquiring membrane materials from other cells. This could therefore account for the different biological consequences of Ag capture via trogocytosis proposed for different types of cells. PMID- 17339462 TI - Genome-wide identification of novel genes involved in early Th1 and Th2 cell differentiation. AB - Th cell subtypes, Th1 and Th2, are involved in the pathogenesis or progression of many immune-mediated diseases, such as type 1 diabetes and asthma, respectively. Defining the molecular networks and factors that direct Th1 and Th2 cell differentiation will help to understand the pathogenic mechanisms causing these diseases. Some of the key factors regulating this differentiation have been identified, however, they alone do not explain the process in detail. To identify novel factors directing the early differentiation, we have studied the transcriptomes of human Th1 and Th2 cells after 2, 6, and 48 h of polarization at the genome scale. Based on our current and previous studies, 288 genes or expressed sequence tags, representing approximately 1-1.5% of the human genome, are regulated in the process during the first 2 days. These transcriptional profiles revealed genes coding for components of certain pathways, such as RAS oncogene family and G protein-coupled receptor signaling, to be differentially regulated during the early Th1 and Th2 cell differentiation. Importantly, numerous novel genes with unknown functions were identified. By using short hairpin RNA knockdown, we show that a subset of these genes is regulated by IL-4 through STAT6 signaling. Furthermore, we demonstrate that one of the IL-4 regulated genes, NDFIP2, promotes IFN-gamma production by the polarized human Th1 lymphocytes. Among the novel genes identified, there may be many factors that play a crucial role in the regulation of the differentiation process together with the previously known factors and are potential targets for developing therapeutics to modulate Th1 and Th2 responses. PMID- 17339463 TI - Characterization of B7S3 as a novel negative regulator of T cells. AB - T cell activation by APCs is regulated by B7-like costimulatory molecules. In this study, we describe a new B7 superfamily member, B7S3, with two differentially spliced isoforms expressed in lymphoid and nonlymphoid tissues. A soluble B7S3-Ig protein bound to professional APC constitutively as well as to activated but not naive T cells. B7S3-Ig treatment greatly inhibited T cell proliferation and IL-2 production. B7S3-Ig also reduced cytokine production by effector T cells. Interestingly, although human genome appears to contain a single-copy B7S3 homolog, the mouse B7S3 gene has 10 relatives within a 2-Mb region constituting a B7S3 gene family. This study identifies B7S3 as a novel negative regulator of T cells, and suggests evolutionarily divergent T cell regulation mechanisms in mammals. PMID- 17339464 TI - Importance of the CD3gamma ectodomain terminal beta-strand and membrane proximal stalk in thymic development and receptor assembly. AB - CD3epsilongamma and CD3epsilondelta are noncovalent heterodimers; each consists of Ig-like extracellular domains associated side-to-side via paired terminal beta strands that are linked to individual subunit membrane proximal stalk segments. CD3epsilon, CD3gamma, and CD3delta stalks contain the RxCxxCxE motif. To investigate the functional importance of a CD3 stalk and terminal beta-strand, we created a CD3gamma double mutant CD3gamma(C82S/C85S) and a CD3gamma beta-strand triple mutant CD3gamma(Q76S/Y78A/Y79A) for use in retroviral transduction of lymphoid progenitors for comparison with CD3gammawt. Although both mutant CD3gamma molecules reduced association with CD3epsilon in CD3epsilongamma heterodimers, CD3gamma(Q76S/Y78A/Y79A) abrogated surface TCR expression whereas CD3gamma(C82S/C85S) did not. Furthermore, CD3gamma(C82S/C85S) rescued thymic development in CD3gamma(-/-) fetal thymic organ culture. However, the numbers of double-positive and single-positive thymocytes after CD3gamma(C82S/C85S) transduction were significantly reduced despite surface pre-TCR and TCR expression comparable to that of CD3gamma(-/-) thymocytes transduced in fetal thymic organ culture with a retrovirus harboring CD3gammawt cDNA. Furthermore, double-negative thymocyte development was perturbed with attenuated double negative 3/double-negative 4 maturation and altered surface-expressed CD3epsilongamma, as evidenced by the loss of reactivity with CD3gamma N terminus specific antisera. Single histidine substitution of either CD3gamma stalk cysteine failed to restore CD3epsilongamma association and conformation in transient COS-7 cell transfection studies. Thus, CD3gamma(C82) and CD3gamma(C85) residues likely are either reduced or form a tight intrachain disulfide loop rather than contribute to a metal coordination site in conjunction with CD3epsilon(C80) and CD3epsilon(C83). The implications of these results for CD3epsilongamma and TCR structure and signaling function are discussed. PMID- 17339465 TI - Normal TCR signal transduction in mice that lack catalytically active PTPN3 protein tyrosine phosphatase. AB - PTPN3 (PTPH1) is a cytoskeletal protein tyrosine phosphatase that has been implicated as a negative regulator of early TCR signal transduction and T cell activation. To determine whether PTPN3 functions as a physiological negative regulator of TCR signaling in primary T cells, we generated gene-trapped and gene targeted mouse strains that lack expression of catalytically active PTPN3. PTPN3 phosphatase-negative mice were born in expected Mendelian ratios and exhibited normal growth and development. Furthermore, numbers and ratios of T cells in primary and secondary lymphoid organs were unaffected by the PTPN3 mutations and there were no signs of spontaneous T cell activation in the mutant mice with increasing age. TCR-induced signal transduction, cytokine production, and proliferation was normal in PTPN3 phosphatase-negative mice. This was observed using both quiescent T cells and recently stimulated T cells where expression of PTPN3 is substantially up-regulated. We conclude, therefore, that the phosphatase activity of PTPN3 is dispensable for negative regulation of TCR signal transduction and T cell activation. PMID- 17339466 TI - Messenger RNA expression of IL-8, FOXP3, and IL-12beta differentiates latent tuberculosis infection from disease. AB - Differentiation of active from latent tuberculosis (TB) is a major challenge in the control of TB. In this study, PBMC from latent TB-infected subjects, TB patients, and tuberculin skin test-negative donors stimulated with the Mycobacterium tuberculosis (Mtb)-specific Ag, early secretory antigenic target 6, and mRNA for 45 immune-related genes was measured by quantitative real-time PCR. Univariate analysis showed significant differences in the expression of 10 genes (IFN-gamma, FOXP3, IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, IL-12alpha, IL-12beta, and IL-24) in PBMC from TB patients vs latent TB-infected subjects (p < 0.01). Multivariate logistic regression and classification and regression tree analyses revealed that expression of three genes, IL-8, FOXP3, and IL-12beta, is predictive for TB vs latent Mtb infection. Thus, measurement of Ag-specific expression of these three genes may offer a specific and noninvasive means of differentiating between latent Mtb infection and TB. PMID- 17339467 TI - Induction of protective immunity to Listeria monocytogenes in neonates. AB - Neonates suffer unduly from infections and also respond suboptimally to most commonly used vaccines. However, a CD8 T cell response can be elicited in neonates if the Ag is introduced into the cytoplasm of APCs. Listeria monocytogenes (Lm) targets the cytoplasm of APC and is a strong CD8 and CD4 Th1 promoting vaccine vehicle in adult mice. We hypothesized that an attenuated strain of Lm would be safe and induce long-lasting protective immunity, even in neonates. We found that neonatal mice immunized only once with the attenuated strain DeltaactA-Lm developed robust primary and secondary CD8 and CD4 Th1 responses and were fully protected from lethal challenge with virulent wild-type Lm without the need for a booster immunization. Furthermore, DeltaactA-Lm expressing a heterologous recombinant Ag induced a strong CD8 and Th1 memory response to that Ag. Based on these data, we propose that DeltaactA-Lm or derivatives thereof might serve as a vaccine vehicle for neonatal immunization. PMID- 17339468 TI - Enhanced defense against Pneumocystis carinii mediated by a novel dectin-1 receptor Fc fusion protein. AB - Pneumocystis carinii (PC) pneumonia is a leading opportunistic infection found among HIV-infected individuals worldwide. Although CD4(+) T cell deficiency clearly correlates with susceptibility to PC pneumonia, murine models of disease indicate that PC-directed Abs may prevent infection and/or inhibit growth of existing PC within the lungs. Recognition of PC by alveolar macrophages involves the beta-glucan receptor Dectin-1 and macrophage effector function against PC is enhanced by Abs derived from PC-vaccinated hosts. We developed a fusion protein consisting of the extracellular domain of Dectin-1 linked to the Fc portion of murine IgG1, which we hypothesized would enhance host recognition and opsonic phagocytosis of PC. The recombinant protein, Dectin-Fc, is dimeric and the Ag recognition site identifies beta-1,3 glucan linkages specifically and with high affinity (K(D) = 2.03 x 10(-7) M). Dectin-Fc enhances RAW264.7 macrophage recognition of the beta-glucan containing particulate zymosan in an FcgammaRII- and FcgammaRIII-dependent manner and preopsonization of PC organisms with Dectin Fc increased alveolar and peritoneal macrophage-dependent killing of PC. SCID mice treated with a replication incompetent adenoviral vector expressing Dectin Fc had attenuated growth of PC within the lungs, overall decreased PC lung burden, and diminished correlates of PC-related lung damage relative to SCID mice receiving a control vector. These findings demonstrate that targeting PC beta glucan with Dectin-Fc enhances host recognition and clearance of PC in the absence of B and T cells, and suggest that FcgammaR-based targeting of PC, via cell wall carbohydrate recognition, may promote resistance against PC pneumonia in the immunodeficient host. PMID- 17339469 TI - Staphylococcus aureus-derived staphopain B, a potent cysteine protease activator of plasma chemerin. AB - Chemerin is an attractant for cells that express the serpentine receptor CMKLR1, which include immature plasmacytoid dendritic cells (pDC) and macrophages. Chemerin circulates in the blood where it exhibits low biological activity, but upon proteolytic cleavage of its C terminus, it is converted to a potent chemoattractant. Enzymes that contribute to this conversion include host serine proteases of the coagulation, fibrinolytic, and inflammatory cascades, and it has been postulated that recruitment of pDC and macrophages by chemerin may serve to balance local tissue immune and inflammatory responses. In this work, we describe a potent, pathogen-derived proteolytic activity capable of chemerin activation. This activity is mediated by staphopain B (SspB), a cysteine protease secreted by Staphylococcus aureus. Chemerin activation is triggered by growth medium of clinical isolates of SspB-positive S. aureus, but not by that of a SspB(null) mutant. C-terminal processing by SspB generates a chemerin isoform identical with the active endogenous attractant isolated from human ascites fluid. Interestingly, SspB is a potent trigger of chemerin even in the presence of plasma inhibitors. SspB may help direct the recruitment of specialized host cells, including immunoregulatory pDC and/or macrophages, contributing to the ability of S. aureus to elicit and maintain a chronic inflammatory state. PMID- 17339470 TI - Synergistic effect of bacillus calmette guerin and a tuberculosis subunit vaccine in cationic liposomes: increased immunogenicity and protection. AB - In the present work, we evaluated a new TB vaccine approach based on a combination of the Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine and a subunit vaccine consisting of the proteins Ag85B and ESAT-6. We demonstrate that in addition to its vaccine efficacy BCG is an immune modulator that can potentiate a Th1 immune response better than the well-known adjuvant mono phosphoryl lipid A, leading to enhanced recognition of the subunit vaccine Ag85B ESAT-6. Importantly, adding a vehicle to the vaccine, such as the cationic liposome dimethyl dioctadecyl ammonium bromide (DDA), significantly increased the potentiating effect of BCG. This synergistic effect between BCG and Ag85B-ESAT 6/liposome required drainage to the same lymph node of all vaccine components but did not require direct mixing of the components and was therefore also observed when BCG and Ag85B-ESAT-6/liposome were given as separate injections at sites draining to the same lymph node. The resulting optimized vaccine protocol consisting of BCG and subunit in liposomes (injected side by side) followed by boosting with the subunit in conventional adjuvant resulted in an impressive increase in the protective efficacy of up to 7-fold compared with BCG alone and 3 fold compared with unaugmented BCG boosted by the subunit vaccine. Thus, these studies suggest an immunization strategy where a novel TB subunit vaccine is administered as part of the child vaccination program together with BCG in neonates and followed by subunit boosting. PMID- 17339471 TI - TLR4-mediated survival of macrophages is MyD88 dependent and requires TNF-alpha autocrine signalling. AB - Modulation of macrophage survival is a critical factor in the resolution of inflammatory responses. Exposure to LPS protects innate immune cells against apoptosis, although the precise pathways responsible for prolongation of macrophage survival remain to be fully established. The goal of this study was to characterize the mechanism of TLR4-mediated survival of murine bone marrow derived macrophages upon M-CSF withdrawal in more detail. Using a combination of knockout mice and pharmacological inhibitors allowed us to show that TLR4 and TLR2 stimulation promotes long-term survival of macrophages in a MyD88-, PI3K-, ERK-, and NF-kappaB-dependent manner. LPS-induced long-term, but not short-term, survival requires autocrine signaling via TNF-alpha and is facilitated by a general cytoprotective program, similar to that mediated by M-CSF. TLR4-mediated macrophage survival is accompanied by a remarkable up-regulation of specific cell surface markers, suggesting that LPS stimulation leads to the differentiation of macrophages toward a mixed macrophage/dendritic cell-like phenotype. PMID- 17339472 TI - MyD88- and Bruton's tyrosine kinase-mediated signals are essential for T cell independent pathogen-specific IgM responses. AB - Bacteremia is one of the leading causes of death by infectious disease. To understand the immune mechanisms required for the rapid control of bacteremia, we studied Borrelia hermsii, a bacterial pathogen that colonizes the blood stream of humans and rodents to an extremely high density. A T cell-independent IgM response is essential and sufficient for controlling B. hermsii bacteremia. Mice deficient in Bruton's tyrosine kinase (Btk), despite their known defect in BCR signaling, generated B. hermsii-specific IgM and resolved bacteremia, suggesting that an alternative activation or costimulatory pathway remained functional for T cell-independent B cells in Btk(-/-) mice. B. hermsii contains putative ligands for TLRs, and we found that mice deficient in TLR1, TLR2, or the TLR adaptor MyD88 generated anti-B. hermsii IgM with delayed kinetics and suffered more severe episodes of bacteremia. In striking contrast to the anti-B. hermsii IgM response in mice deficient only in Btk, mice deficient in both Btk and MyD88 were entirely incapable of generating B. hermsii-specific Ab or resolving bacteremia. The response to a T cell-dependent model Ag was unaffected in Btk(-/-) x MyD88(-/ ) mice. These results suggest that MyD88 specifically promotes T cell-independent BCR signaling and that, in the absence of Btk, this TLR-mediated stimulation is a required component of this signal. PMID- 17339473 TI - Epitope cross-reactivity frequently differs between central and effector memory HIV-specific CD8+ T cells. AB - HIV diversity may limit the breadth of vaccine coverage due to epitope sequence differences between strains. Although amino acid substitutions within CD8(+) T cell HIV epitopes can result in complete or partial abrogation of responses, this has primarily been demonstrated in effector CD8(+) T cells. In an HIV-infected Kenyan cohort, we demonstrate that the cross-reactivity of HIV epitope variants differs dramatically between overnight IFN-gamma and longer-term proliferation assays. For most epitopes, particular variants (not the index peptide) were preferred in proliferation in the absence of corresponding overnight IFN-gamma responses and in the absence of the variant in the HIV quasispecies. Most proliferating CD8(+) T cells were polyfunctional via cytokine analyses. A trend to positive correlation was observed between proliferation (but not IFN-gamma) and CD4 counts. We present findings relevant to the assessment of HIV vaccine candidates and toward a better understanding of how viral diversity is tolerated by central and effector memory CD8(+) T cells. PMID- 17339474 TI - Role of the GALT in scrapie agent neuroinvasion from the intestine. AB - Following oral exposure, some transmissible spongiform encephalopathy (TSE) agents accumulate first upon follicular dendritic cells (FDCs) in the GALT. Studies in mice have shown that this accumulation is obligatory for the efficient delivery of the TSE agent to the brain. However, which GALTs are crucial for disease pathogenesis is uncertain. Mice deficient in specific GALT components were used here to determine their separate involvement in scrapie agent neuroinvasion from the intestine. In the combined absence of the GALTs and FDCs (lymphotoxin (LT)alpha(-/-) mice and LTbeta(-/-) mice), scrapie agent transmission was blocked. When FDC maturation was induced in remaining lymphoid tissues, mice that lacked both Peyer's patches (PPs) and mesenteric lymph nodes (wild-type (WT)-->LTalpha(-/-) mice) or PPs alone (WT-->LTbeta(-/-) mice) remained refractory to disease, demonstrating an important role for the PPs. Although early scrapie agent accumulation also occurs within the mesenteric lymph nodes, their presence in WT-->LTbeta(-/-) mice did not restore disease susceptibility. We have also shown that isolated lymphoid follicles (ILFs) are important novel sites of TSE agent accumulation in the intestine. Mice that lacked PPs but contained numerous FDC-containing mature ILFs succumbed to scrapie at similar times to control mice. Because the formation and maturation status of ILFs is inducible and influenced by the gut flora, our data suggest that such factors could dramatically affect susceptibility to orally acquired TSE agents. In conclusion, these data demonstrate that following oral exposure TSE agent accumulation upon FDCs within lymphoid tissue within the intestine itself is critically required for efficient neuroinvasion. PMID- 17339475 TI - Monocyte-dependent fibroblast CXCL8 secretion occurs in tuberculosis and limits survival of mycobacteria within macrophages. AB - CXCL8 is a chemokine that is implicated in the formation of tuberculous (TB) granulomas and in immunity to Mycobacterium tuberculosis (Mtb). Fibroblast chemokine secretion is important for modulating inflammatory responses in chronic lung disease and inflammatory arthritis but has not been investigated in the pathophysiology of TB. In this study, we used a cellular model to examine monocyte/macrophage-dependent stimulation of fibroblasts by Mtb in the regulation of chemokine secretion, particularly that of CXCL8. Human lung fibroblasts grown in collagen were stimulated with conditioned medium from Mtb-infected monocytes (CoMTb). CoMTb-induced prolonged dose-dependent, p38-mediated expression of stable CXCL8 mRNA by fibroblasts accompanied by a >10-fold increase in CXCL8 secretion (487 +/- 88 ng/ml vs 48.6 +/- 34 ng/ml in controls) at 120 h. Fibroblasts strongly expressed CXCL8 in vivo in human TB granulomas. Inhibition of TNF-alpha or IL-1 in CoMTb abrogated the induction of CXCL8 at a pretranscriptional level. CXCL8 secretion was NF-kappaB, C/EBP, and JNK dependent. Sustained NF-kappaB activation was demonstrated beyond 24 h in response to CoMTb. Exogenous CXCL8 reduced the survival of Mtb within macrophages, and inhibition of CXCL8 was associated with intracellular mycobacterial proliferation. These data show that fibroblasts have a previously unrecognized role in modulating inflammation in TB by their CXCL8-dependent contribution to cell recruitment and mycobacterial killing within the granuloma. PMID- 17339476 TI - Overexpression of suppressor of cytokine signaling-3 in T cells exacerbates acetaminophen-induced hepatotoxicity. AB - Cytokines have been implicated in the progression of acetaminophen (APAP)-induced acute liver injury. Suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling by inhibiting the JAK-STAT pathway, but their role in APAP hepatotoxicity is unknown. In this present study, we attempted to explore the role of SOCS3 in T cells in APAP-induced liver injury. Mice with a cell-specific overexpression of SOCS3 in T cells (SOCS3Tg, in which Tg is transgenic) exhibited exaggerated hepatic injury after APAP challenge, as evidenced by increased serum alanine aminotransferase levels, augmented hepatic necrosis, and decreased survival relative to the wild-type mice. Adaptive transfer of SOCS3Tg-CD4(+) T cells into T and B cell-deficient RAG-2(-/-) mice resulted in an exacerbated liver injury relative to the control. In SOCS3Tg mice, hepatocyte apoptosis was enhanced with decreased expression of antiapoptotic protein bcl-2, whereas hepatocyte proliferation was reduced with altered cell cycle-regulatory proteins. Levels of IFN-gamma and TNF-alpha in the circulation were augmented in SOCS3Tg mice relative to the control. Studies using neutralizing Abs indicated that elevated IFN-gamma and TNF-alpha were responsible for the exacerbated hepatotoxicity in SOCS3Tg mice. Activation of STAT1 that is harmful in liver injury was augmented in SOCS3Tg hepatocytes. Alternatively, hepatoprotective STAT3 activation was decreased in SOCS3Tg hepatocytes, an event that was associated with augmented SOCS3 expression in the hepatocytes. Altogether, these results suggest that forced expression of SOCS3 in T cells is deleterious in APAP hepatotoxicity by increasing STAT1 activation while decreasing STAT3 activation in hepatocytes, possibly through elevated IFN-gamma and TNF-alpha. PMID- 17339477 TI - IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. AB - IL-17 is a cytokine that induces neutrophil-mediated inflammation, but its role in protective immunity against intracellular bacterial infection remains unclear. In the present study, we demonstrate that IL-17 is an important cytokine not only in the early neutrophil-mediated inflammatory response, but also in T cell mediated IFN-gamma production and granuloma formation in response to pulmonary infection by Mycobacterium bovis bacille Calmette-Guerin (BCG). IL-17 expression in the BCG-infected lung was detected from the first day after infection and the expression depended on IL-23. Our observations indicated that gammadelta T cells are a primary source of IL-17. Lung-infiltrating T cells of IL-17-deficient mice produced less IFN-gamma in comparison to those from wild-type mice 4 wk after BCG infection. Impaired granuloma formation was also observed in the infected lungs of IL-17-deficient mice, which is consistent with the decreased delayed-type hypersensitivity response of the infected mice against mycobacterial Ag. These data suggest that IL-17 is an important cytokine in the induction of optimal Th1 response and protective immunity against mycobacterial infection. PMID- 17339478 TI - The granulocyte receptor carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) directly associates with Vav to promote phagocytosis of human pathogens. AB - The human granulocyte-specific receptor carcinoembryonic antigen-related cell adhesion molecule (CEACAM)3 is critically involved in the opsonin-independent recognition of several bacterial pathogens. CEACAM3-mediated phagocytosis depends on the integrity of an ITAM-like sequence within the cytoplasmic domain of CEACAM3 and is characterized by rapid stimulation of the GTPase Rac. By performing a functional screen with CEACAM3-expressing cells, we found that overexpression of a dominant-negative form of the guanine nucleotide exchange factor Vav, but not the dominant-negative versions SWAP70, Dock2, or ELMO1 interfered with CEACAM3-initiated phagocytosis. Moreover, small interfering RNA mediated silencing of Vav reduced uptake and abrogated the stimulation of Rac in response to bacterial CEACAM3 engagement. In Vav1/Vav2-deficient cells, CEACAM3 mediated internalization was only observed after re-expression of Vav. Vav colocalized with CEACAM3 upon bacterial infection, coimmunoprecipitated in a complex with CEACAM3, and the Vav Src homology 2 domain directly associated with phosphorylated Tyr(230) of CEACAM3. In primary human granulocytes, TAT-mediated transduction of dominant-negative Vav, but not SWAP70, severely impaired the uptake of CEACAM3-binding bacteria. These data support the view that, different from canonical ITAM signaling, the CEACAM3 ITAM-like sequence short-wires bacterial recognition and Rac stimulation via a direct association with Vav to promote rapid phagocytosis and elimination of CEACAM-binding human pathogens. PMID- 17339479 TI - H2-M3-restricted CD8+ T cells induced by peptide-pulsed dendritic cells confer protection against Mycobacterium tuberculosis. AB - One of the oligopolymorphic MHC class Ib molecules, H2-M3, presents N-formylated peptides derived from bacteria. In this study, we tested the ability of an H2-M3 binding peptide, TB2, to induce protection in C57BL/6 mice against Mycobacterium tuberculosis. Immunization with bone marrow-derived dendritic cell (BMDC) pulsed with TB2 or a MHC class Ia-binding peptide, MPT64(190-198) elicited an expansion of Ag-specific CD8+ T cells in the spleen and the lung. The number of TB2 specific CD8+ T cells reached a peak on day 6, contracted with kinetics similar to MPT64(190-198)-specific CD8+ T cells and was maintained at an appreciable level for at least 60 days. The TB2-specific CD8+ T cells produced less effector cytokines but have stronger cytotoxic activity than MPT64(190-198)-specific CD8+ T cells. Mice immunized with TB2-pulsed BMDC as well as those with MPT64(190-198) pulsed BMDC showed significant protection against an intratracheal challenge with M. tuberculosis H37Rv. However, histopathology of the lung in mice immunized with TB2-pulsed BMDC was different from mice immunized with MPT64(190-198)-pulsed BMDC. Our results suggest that immunization with BMDC pulsed with MHC class Ib restricted peptides would be a useful vaccination strategy against M. tuberculosis. PMID- 17339480 TI - Catalase overexpression fails to attenuate allergic airways disease in the mouse. AB - Oxidative stress is a hallmark of asthma, and increased levels of oxidants are considered markers of the inflammatory process. Most studies to date addressing the role of oxidants in the etiology of asthma were based on the therapeutic administration of low m.w. antioxidants or antioxidant mimetic compounds. To directly address the function of endogenous hydrogen peroxide in the pathophysiology of allergic airway disease, we comparatively evaluated mice systemically overexpressing catalase, a major antioxidant enzyme that detoxifies hydrogen peroxide, and C57BL/6 strain matched controls in the OVA model of allergic airways disease. Catalase transgenic mice had 8-fold increases in catalase activity in lung tissue, and had lowered DCF oxidation in tracheal epithelial cells, compared with C57BL/6 controls. Despite these differences, both strains showed similar increases in OVA-specific IgE, IgG1, and IgG2a levels, comparable airway and tissue inflammation, and identical increases in procollagen 1 mRNA expression, following sensitization and challenge with OVA. Unexpectedly, mRNA expression of MUC5AC and CLCA3 genes were enhanced in catalase transgenic mice, compared with C57BL/6 mice subjected to Ag. Furthermore, when compared with control mice, catalase overexpression increased airway hyperresponsiveness to methacholine both in naive mice as well as in response to Ag. In contrast to the prevailing notion that hydrogen peroxide is positively associated with the etiology of allergic airways disease, the current findings suggest that endogenous hydrogen peroxide serves a role in suppressing both mucus production and airway hyperresponsiveness. PMID- 17339481 TI - IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL 21R.Fc reduces disease progression. AB - Systemic lupus erythematosus is a complex autoimmune disease characterized by dysregulated interactions between autoreactive T and B lymphocytes and the development of anti-nuclear Abs. The recently described pleiotropic cytokine IL 21 has been shown to regulate B cell differentiation and function. IL-21 is produced by activated T lymphocytes and its interactions with IL-21R are required for isotype switching and differentiation of B cells into Ab-secreting cells. In this report, we studied the impact of blocking IL-21 on disease in the lupus prone MRL-Fas(lpr) mouse model. Mice treated for 10 wk with IL-21R.Fc fusion protein had reduced proteinuria, fewer IgG glomerular deposits, no glomerular basement membrane thickening, reduced levels of circulating dsDNA autoantibodies and total sera IgG1 and IgG2a, and reduced skin lesions and lymphadenopathy, compared with control mice. Also, treatment with IL-21R.Fc resulted in a reduced number of splenic T lymphocytes and altered splenic B lymphocyte ex vivo function. Our data show for the first time that IL-21 has a pathogenic role in the MRL-Fas(lpr) lupus model by impacting B cell function and regulating the production of pathogenic autoantibodies. From a clinical standpoint, these results suggest that blocking IL-21 in systemic lupus erythematosus patients may represent a promising novel therapeutic approach. PMID- 17339482 TI - Y402H polymorphism of complement factor H affects binding affinity to C-reactive protein. AB - Complement factor H (FH) is an important regulator of the alternative complement pathway. The Y402H polymorphism within the seventh short consensus repeat of FH was recently shown to be associated with age-related macular degeneration, the most common cause of irreversible blindness in the Western world. We examined the effects of this polymorphism on various FH functions. FH purified from sera of age-related macular degeneration patients homozygous for the FH(402H) variant showed a significantly reduced binding to C-reactive protein (CRP), an acute phase protein, as compared with FH derived from unaffected controls homozygous for the FH(402Y) variant. Strongly reduced binding to CRP was also observed with a recombinant fragment of FH (short consensus repeat 5-7) containing the same amino acid change. Because the interaction of CRP and FH promotes complement mediated clearance of cellular debris in a noninflammatory fashion, we propose that the reduced binding of FH(402H) to CRP could lead to an impaired targeting of FH to cellular debris and a reduction in debris clearance and enhanced inflammation along the macular retinal pigmented epithelium-choroid interface in individuals with age-related macular degeneration. PMID- 17339483 TI - Pyrin-only protein 2 modulates NF-kappaB and disrupts ASC:CLR interactions. AB - NF-kappaB is pivotal for transactivation of cell-cycle regulatory, cytokine, and adhesion molecule genes and is dysregulated in many cancers, neurodegenerative disorders, and inflammatory diseases. Proteins with pyrin and/or caspase recruitment domains have roles in apoptosis, innate immunity, and inflammation. Many pyrin domain (PYD) proteins modulate NF-kappaB activity as well as participate in assembling both the perinuclear "apoptotic speck" and the pro IL1beta/IL-18-converting inflammasome complex. "Pyrin-only" proteins (POP) are attractive as negative regulators of PYD-mediated functions and one such protein, POP1, has been reported. We report the identification and initial characterization of a second POP. POP2 is a 294 nt single exon gene located on human chromosome 3 encoding a 97-aa protein with sequence and predicted structural similarity to other PYDs. Highly similar to PYDs in CATERPILLER (CLR, NLR, NALP) family proteins, POP2 is less like the prototypic pyrin and ASC PYDs. POP2 is expressed principally in peripheral blood leukocytes and displays both cytoplasmic and nuclear expression patterns in transfected cells. TNF-alpha stimulated and p65 (RelA)-induced NF-kappaB-dependent gene transcription is inhibited by POP2 in vitro by a mechanism involving changes in NF-kappaB nuclear import or distribution. While colocalizing with ASC in perinuclear specks, POP2 also inhibits the formation of specks by the CLR protein CIAS1/NALP3. Together, these observations demonstrate that POP2 is a negative regulator of NF-kappaB activity that may influence the assembly of PYD-dependent complexes. PMID- 17339484 TI - A novel pathway that regulates inflammatory disease in the respiratory tract. AB - In animals with acute airway inflammation followed by repeated exposure to inhaled Ag, inflammation wanes over time and thus limits the study of chronic airway inflammatory diseases such as asthma. We developed a model of airway inflammation and inhalational exposure to investigate regulatory pathways in the respiratory tract. We show that Th1- and Th2-induced airway inflammation followed by repeated exposure to inhaled Ag leads to a state of immunosuppression. Challenge of these animals with a marked population of TCR transgenic effector Th1 or Th2 cells results in a striking inhibition of inflammation and effector Th cells. In Th2 models, airway hyperresponsiveness, mucus, and eosinophilia are reduced. The inhibitory effects observed are Ag nonspecific, can be induced in lymphocyte-deficient mice, and are associated with a population of TGF-beta1 expressing macrophages. Induction of this pathway may offer potent localized treatment of chronic T cell-mediated respiratory illnesses and provide insights into the development of such diseases. PMID- 17339485 TI - A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1. AB - The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release early (e.g., TNF, IL-1, and IFN-gamma) and late (e.g., high mobility group box 1 (HMGB1) protein) proinflammatory cytokines. The recent discovery of HMGB1 as a late mediator of lethal sepsis has prompted investigation for development of new experimental therapeutics. We found that many steroidal drugs (such as dexamethasone and cortisone) and nonsteroidal anti-inflammatory drugs (such as aspirin, ibuprofen, and indomethacin) failed to influence endotoxin-induced HMGB1 release even at superpharmacological concentrations (up to 10-25 microM). However, several steroid-like pigments (tanshinone I, tanshinone IIA, and cryptotanshinone) of a popular Chinese herb, Danshen (Salvia miltiorrhiza), dose dependently attenuated endotoxin-induced HMGB1 release in macrophage/monocyte cultures. A water-soluble tanshinone IIA sodium sulfonate derivative (TSNIIA-SS), which has been widely used as a Chinese medicine for patients with cardiovascular disorders, selectively abrogated endotoxin-induced HMGB1 cytoplasmic translocation and release in a glucocorticoid receptor-independent manner. Administration of TSNIIA SS significantly protected mice against lethal endotoxemia and rescued mice from lethal sepsis even when the first dose was given 24 h after the onset of sepsis. The therapeutic effects were partly attributable to attenuation of systemic accumulation of HMGB1 (but not TNF and NO) and improvement of cardiovascular physiologic parameters (e.g., decrease in total peripheral vascular resistance and increase in cardiac stroke volume) in septic animals. Taken together, these data re-enforce the pathogenic role of HMGB1 in lethal sepsis, and support a therapeutic potential for TSNIIA-SS in the treatment of human sepsis. PMID- 17339486 TI - VCAM-1 activation of endothelial cell protein tyrosine phosphatase 1B. AB - Lymphocytes migrate from the blood into tissue by binding to and migrating across endothelial cells. One of the endothelial cell adhesion molecules that mediate lymphocyte binding is VCAM-1. We have reported that binding to VCAM-1 activates endothelial cell NADPH oxidase for the generation of reactive oxygen species (ROS). The ROS oxidize and stimulate an increase in protein kinase C (PKC)alpha activity. Furthermore, these signals are required for VCAM-1-dependent lymphocyte migration. In this report, we identify a role for protein tyrosine phosphatase 1B (PTP1B) in the VCAM-1 signaling pathway. In primary cultures of endothelial cells and endothelial cell lines, Ab cross-linking of VCAM-1 stimulated an increase in serine phosphorylation of PTP1B, the active form of PTP1B. Ab cross-linking of VCAM-1 also increased activity of PTP1B. This activation of PTP1B was downstream of NADPH oxidase and PKCalpha in the VCAM-1 signaling pathway as determined with pharmacological inhibitors and antisense approaches. In addition, during VCAM-1 signaling, ROS did not oxidize endothelial cell PTP1B. Instead PTP1B was activated by serine phosphorylation. Importantly, inhibition of PTP1B activity blocked VCAM-1-dependent lymphocyte migration across endothelial cells. In summary, VCAM-1 activates endothelial cell NADPH oxidase to generate ROS, resulting in oxidative activation of PKCalpha and then serine phosphorylation of PTP1B. This PTP1B activity is necessary for VCAM-1-dependent transendothelial lymphocyte migration. These data show, for the first time, a function for PTP1B in VCAM-1-dependent lymphocyte migration. PMID- 17339487 TI - The Src family kinases Hck and Fgr regulate neutrophil responses to N-formyl methionyl-leucyl-phenylalanine. AB - The chemotactic peptide formyl-methionyl-leucyl-phenilalanine (fMLP) triggers intracellular protein tyrosine phosphorylation leading to neutrophil activation. Deficiency of the Src family kinases Hck and Fgr have previously been found to regulate fMLP-induced degranulation. In this study, we further investigate fMLP signaling in hck-/-fgr-/- neutrophils and find that they fail to activate a respiratory burst and display reduced F-actin polymerization in response to fMLP. Additionally, albeit migration of both hck-/-fgr-/-mouse neutrophils and human neutrophils incubated with the Src family kinase inhibitor 4-amino-5-(4 chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) through 3-microm pore size Transwells was normal, deficiency, or inhibition, of Src kinases resulted in a failure of neutrophils to migrate through 1-microm pore size Transwells. Among MAPKs, phosphorylation of ERK1/2 was not different, phosphorylation of p38 was only partially affected, and phosphorylation of JNK was markedly decreased in fMLP-stimulated hck-/-fgr-/- neutrophils and in human neutrophils incubated with PP2. An increase in intracellular Ca(2+) concentration and phosphorylation of Akt/PKB occurred normally in fMLP-stimulated hck-/-fgr-/- neutrophils, indicating that activation of both phosphoinositide-specific phospholipase C and PI3K is independent of Hck and Fgr. In contrast, phosphorylation of the Rho/Rac guanine nucleotide exchange factor Vav1 and the Rac target p21-activated kinases were markedly reduced in both hck-/-fgr-/- neutrophils and human neutrophils incubated with a PP2. Consistent with these findings, PP2 inhibited Rac2 activation in human neutrophils. We suggest that Hck and Fgr act within a signaling pathway triggered by fMLP receptors that involves Vav1 and p21-activated kinases, leading to respiratory burst and F-actin polymerization. PMID- 17339488 TI - Variable requirement of dendritic cells for recruitment of NK and T cells to different TLR agonists. AB - TLRs initiate the host immune response to microbial pathogens by activating cells of the innate immune system. Dendritic cells (DCs) can be categorized into two major groups, conventional DCs (including CD8(+) and CD8(-) DCs) and plasmacytoid DCs. In mice, these subsets of DCs express a variety of TLRs, with conventional DCs responding in vitro to predominantly TLR3, TLR4, TLR5, and TLR9 ligands, and plasmacytoid DCs responding mainly to TLR7 and TLR9 ligands. However, the in vivo requirement of DCs to initiate immune responses to specific TLR agonists is not fully known. Using mice depleted of >90% of CD11c(+) MHC class II(+) DCs, we demonstrate that cellular recruitment, including CD4(+) T cell and CX5(+)DX5(+) NK cell recruitment to draining lymph nodes following the footpad administration of TLR4 and TLR5 agonists, is dramatically decreased upon reduction of DC numbers, but type I IFN production can partially substitute for DCs in response to TLR3 and TLR7 agonists. Interestingly, TLR ligands can activate T cells and NK cells in the draining lymph nodes, even with reduced DC numbers. The findings reveal considerable plasticity in the response to TLR agonists, with TLR4 and TLR5 agonists sharing the requirement of DCs for subsequent lymph node recruitment of NK and T cells. PMID- 17339489 TI - A quantitative study of NF-kappaB activation by H2O2: relevance in inflammation and synergy with TNF-alpha. AB - Although the germicide role of H(2)O(2) released during inflammation is well established, a hypothetical regulatory function, either promoting or inhibiting inflammation, is still controversial. In particular, after 15 years of highly contradictory results it remains uncertain whether H(2)O(2) by itself activates NF-kappaB or if it stimulates or inhibits the activation of NF-kappaB by proinflammatory mediators. We investigated the role of H(2)O(2) in NF-kappaB activation using, for the first time, a calibrated and controlled method of H(2)O(2) delivery--the steady-state titration--in which cells are exposed to constant, low, and known concentrations of H(2)O(2). This technique contrasts with previously applied techniques, which disrupt cellular redox homeostasis and/or introduce uncertainties in the actual H(2)O(2) concentration to which cells are exposed. In both MCF-7 and HeLa cells, H(2)O(2) at extracellular concentrations up to 25 microM did not induce significantly per se NF-kappaB translocation to the nucleus, but it stimulated the translocation induced by TNF alpha. For higher H(2)O(2) doses this stimulatory role shifts to an inhibition, which may explain published contradictory results. The stimulatory role was confirmed by the observation that 12.5 microM H(2)O(2), a concentration found during inflammation, increased the expression of several proinflammatory NF kappaB-dependent genes induced by TNF-alpha (e.g., IL-8, MCP-1, TLR2, and TNF alpha). The same low H(2)O(2) concentration also induced the anti-inflammatory gene coding for heme oxygenase-1 (HO-1) and IL-6. We propose that H(2)O(2) has a fine-tuning regulatory role, comprising both a proinflammatory control loop that increases pathogen removal and an anti-inflammatory control loop, which avoids an exacerbated harmful inflammatory response. PMID- 17339490 TI - Immobilized stromal cell-derived factor-1alpha triggers rapid VLA-4 affinity increases to stabilize lymphocyte tethers on VCAM-1 and subsequently initiate firm adhesion. AB - The integrin VLA-4 (alpha(4)beta(1)) mediates tethering and rolling events as well as firm adhesion of leukocytes to VCAM-1. Unlike selectins, VLA-4 integrin mediated lymphocyte adhesiveness can be modulated by chemokines through intracellular signaling pathways. To investigate the effects of the chemokine stromal cell-derived factor-1alpha (SDF-1alpha) on VLA-4-mediated lymphocyte adhesion, human PBL were flowed over VCAM-1 substrates in a parallel plate flow chamber with surface-immobilized SDF-1alpha, a potent activator of firm adhesion. The initial tethering interactions had a median lifetime of 200 ms, consistent with the half-life of low-affinity VLA-4-VCAM-1 bonds. Immobilized SDF-1alpha acted within the lifetime of a primary tether to stabilize initial tethering interactions, increasing the likelihood a PBL would remain interacting with the surface. As expected, the immobilized SDF-1alpha also increased the ratio of PBL firm adhesion to rolling. An LDV peptide-based small molecule that preferentially binds high-affinity VLA-4 reduced PBL firm adhesion to VCAM-1 by 90%. The reduction in firm adhesion due to blockage of high-affinity VLA-4 was paralleled by a 4-fold increase in the fraction of rolling PBL. Chemokine activation of PBL firm adhesion on VCAM-1 depended on induction of high-affinity VLA-4 rather than recruitment of a pre-existing pool of high-affinity VLA-4 as previously thought. PMID- 17339491 TI - Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. AB - Resolvin E1 (RvE1) is a potent anti-inflammatory and proresolving mediator derived from omega-3 eicosapentaenoic acid generated during the resolution phase of inflammation. RvE1 possesses a unique structure and counterregulatory actions that stop human polymorphonuclear leukocyte (PMN) transendothelial migration and PMN infiltration in several murine inflammatory models. To examine the mechanism(s) underlying anti-inflammatory actions on PMNs, we prepared [(3)H]RvE1 and characterized its interactions with human PMN. Results with membrane fractions of human PMN demonstrated specific binding with a K(d) of 48.3 nM. [(3)H]RvE1 specific binding to human PMN was displaced by leukotriene B(4) (LTB(4)) and LTB(4) receptor 1 (BLT1) antagonist U-75302, but not by chemerin peptide, a ligand specific for another RvE1 receptor ChemR23. Recombinant human BLT1 gave specific binding with [(3)H]RvE1 with a K(d) of 45 nM. RvE1 selectively inhibited adenylate cyclase with BLT1, but not with BLT2. In human PBMC, RvE1 partially induced calcium mobilization, and blocked subsequent stimulation by LTB(4). RvE1 also attenuated LTB(4)-induced NF-kappaB activation in BLT1 transfected cells. In vivo anti-inflammatory actions of RvE1 were sharply reduced in BLT1 knockout mice when given at low doses (100 ng i.v.) in peritonitis. In contrast, RvE1 at higher doses (1.0 mug i.v.) significantly reduced PMN infiltration in a BLT1-independent manner. These results indicate that RvE1 binds to BLT1 as a partial agonist, potentially serving as a local damper of BLT1 signals on leukocytes along with other receptors (e.g., ChemR23-mediated counterregulatory actions) to mediate the resolution of inflammation. PMID- 17339492 TI - Relevance of C1 and C2 epitopes for hemopoietic stem cell transplantation: role for sequential acquisition of HLA-C-specific inhibitory killer Ig-like receptor. AB - Killer Ig-like receptors (KIR) and HLA class I ligands were studied in unrelated hemopoietic stem cell transplantation for chronic myeloid leukemia (n = 108). Significantly improved overall survival was observed in patients, which were homozygous for HLA-C-encoded group 1 (C1) ligands compared with those with group 2 (C2) ligands. Favorable outcome in the former patient group was an early effect that was highly significant in patients transplanted with G-CSF-mobilized peripheral blood and patients with advanced disease stages. In contrast, presence of C1 ligands in the donor was associated with significantly reduced patient survival. The differential roles of the two HLA-C ligands are explained in the context of a biased NK cell reconstitution, which is generally dominated by the presence of C1- but absence of C2-specific NK cells. The clinical observations are corroborated by in vitro experiments showing that NK cells derived from hemopoietic progenitor cells generally acquire the C1-specific inhibitory KIR2DL2/3 at earlier time points and with higher frequency than the C2-specific KIR2DL1. These findings define a novel determinant for understanding the role of NK cells in clinical hemopoietic stem cell transplantation. PMID- 17339493 TI - Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy. AB - Type I allergy is characterized by the development of an initial Th2-dependent allergen-specific IgE response, which is boosted upon a subsequent allergen encounter. Although the immediate symptoms of allergy are mainly IgE-mediated, allergen-specific T cell responses contribute to the late phase as well as to the chronic manifestations of allergy. This study investigates the potential of costimulation blockade with CTLA4Ig and an anti-CD154 mAb for modifying the allergic immune response to the major timothy grass pollen allergen Phl p 5 in a mouse model. BALB/c mice were treated with the costimulation blockers at the time of primary sensitization to the Phl p 5 allergen or at the time of a secondary allergen challenge. Costimulation blockade (CTLA4Ig plus anti-CD154 or anti-CD154 alone) at the time of sensitization prevented the development of allergen specific IgE, IgM, IgG, and IgA responses compared with untreated but sensitized mice. However, costimulation blockade had no influence on established IgE responses in sensitized mice. Immediate-type reactions as analyzed by a rat basophil leukemia cell mediator release assay were only suppressed by early treatment but not by a costimulation blockade after sensitization. CTLA4Ig given alone failed to suppress both the primary and the secondary allergen-specific Ab responses. Allergen-specific T cell activation was suppressed in mice by early as well as by a late costimulation blockade, suggesting that IgE responses in sensitized mice are independent of T cell help. Our results indicate that T cell suppression alone without active immune regulation or a shifting of the Th2/Th1 balance is not sufficient for the treatment of established IgE responses in an allergy. PMID- 17339494 TI - Unravelling the complexity of T cell abnormalities in common variable immunodeficiency. AB - We investigated several phenotypic and functional parameters of T cell-mediated immunity in a large series of common variable immunodeficiency (CVID) patients. We demonstrated that the vast majority of CVID patients presented multiple T cell abnormalities intimately related among them, the severity of which was reflected in a parallel loss of CD4+ naive T cells. A strong correlation between the number of CD4+ naive T cells and clinical features was observed, supporting the subgrouping of patients according to their number of naive CD4+ T lymphocytes. A reduced thymic output and disrupted CD4+ and CD8+ TCR repertoires paralleled the contraction of CD4+ naive T cell pools. The evaluation of activation markers and cytokine production indicated a strong T cell activation that was significantly related to the increased levels of T cell turnover and apoptosis. Finally, discrete genetic profiles could be demonstrated in groups of patients showing extremely diverse T cell subset composition and function. Naive CD4+ T cell levels were significantly associated with the switched memory B cell-based classification, although the concordance between the respective subgroups did not exceed 58.8%. In conclusion, our data highlight the key role played by the T cell compartment in the pathogenesis of CVID, pointing to the need to consider this aspect for classification of this disease. PMID- 17339495 TI - Fever-like hyperthermia controls T Lymphocyte persistence by inducing degradation of cellular FLIPshort. AB - Fever has a major impact on immune responses by modulating survival, proliferation, and endurance of lymphocytes. Lymphocyte persistence in turn is determined by the equilibrium between death and survival-promoting factors that regulate death receptor signaling in these cells. A potential integrator of death receptor signaling is the caspase-8 inhibitor c-FLIP, the expression of which is dynamically regulated, either rapidly induced or down-regulated. In this study, we show in activated primary human T lymphocytes that hyperthermia corresponding to fever triggered down-regulation of both c-FLIP-splicing variants, c-FLIPshort (c-FLIP(S)) and c-FLIPlong, with consequent sensitization to apoptosis mediated by CD95 (Fas/APO-1). The c-FLIP down-regulation and subsequent sensitization was specific for hyperthermic stress. Additionally, we show that the hyperthermia mediated down-regulation was due to increased ubiquitination and proteasomal degradation of c-FLIP(S), the stability of which we have shown to be regulated by its C-terminal splicing tail. Furthermore, the induced sensitivity to CD95 ligation was independent of heat shock protein 70, as thermotolerant cells, expressing substantially elevated levels of heat shock protein 70, were not rescued from the effect of hyperthermia-mediated c-FLIP down-regulation. Our findings indicate that fever significantly influences the rate of lymphocyte elimination through depletion of c-FLIP(S). Such a general regulatory mechanism for lymphocyte removal has broad ramifications for fever-mediated regulation of immune responses. PMID- 17339496 TI - Disruption of CD36 impairs cytokine response to Plasmodium falciparum glycosylphosphatidylinositol and confers susceptibility to severe and fatal malaria in vivo. AB - CD36 is a scavenger receptor that has been implicated in malaria pathogenesis as well as innate defense against blood-stage infection. Inflammatory responses to Plasmodium falciparum GPI (pfGPI) anchors are believed to play an important role in innate immune response to malaria. We investigated the role of CD36 in pfGPI induced MAPK activation and proinflammatory cytokine secretion. Furthermore, we explored the role of this receptor in an experimental model of acute malaria in vivo. We demonstrate that ERK1/2, JNK, p38, and c-Jun became phosphorylated in pfGPI-stimulated macrophages. In contrast, pfGPI-induced phosphorylation of JNK, ERK1/2, and c-Jun was reduced in Cd36(-/-) macrophages and Cd36(-/-) macrophages secreted significantly less TNF-alpha in response to pfGPI than their wild-type counterparts. In addition, we demonstrate a role for CD36 in innate immune response to malaria in vivo. Compared with wild-type mice, Cd36(-/-) mice experienced more severe and fatal malaria when challenged with Plasmodium chabaudi chabaudi AS. Cd36(-/-) mice displayed a combined defect in cytokine induction and parasite clearance with a dysregulated cytokine response to infection, earlier peak parasitemias, higher parasite densities, and higher mortality rates than wild-type mice. These results provide direct evidence that pfGPI induces TNF-alpha secretion in a CD36-dependent manner and support a role for CD36 in modulating host cytokine response and innate control of acute blood stage malaria infection in vivo. PMID- 17339497 TI - T cell TRAIL promotes murine lupus by sustaining effector CD4 Th cell numbers and by inhibiting CD8 CTL activity. AB - T cells play an essential role in driving humoral autoimmunity in lupus. Molecules such as TRAIL exhibit strong T cell modulatory effects and are up regulated in lupus, raising the possibility that they may influence disease severity. To address this possibility, we examined the role of TRAIL expression on pathogenic T cells in an induced model of murine lupus, the parent-into-F(1) (P-->F(1)) model of chronic graft-vs-host disease (GVHD), using wild-type or TRAIL-deficient donor T cells. Results were compared with mice undergoing suppressive acute GVHD. Although chronic GVHD mice exhibited less donor T cell TRAIL up-regulation and IFN-alpha-inducible gene expression than acute GVHD mice, donor CD4(+) T cell TRAIL expression in chronic GVHD was essential for sustaining effector CD4(+) Th cell numbers, for sustaining help to B cells, and for more severe lupus-like renal disease development. Conversely, TRAIL expression on donor CD8(+) T cells had a milder, but significant down-regulatory effect on CTL effector function, affecting the perforin/granzyme pathway and not the Fas ligand pathway. These results indicate that, in this model, T cell-expressed TRAIL exacerbates lupus by the following: 1) positively regulating CD4(+) Th cell numbers, thereby sustaining T cell help for B cells, and 2) to a lesser degree by negatively regulating perforin-mediated CD8(+) CTL killing that could potentially eliminate activated autoreactive B cells. PMID- 17339498 TI - FcalphaRI (CD89) alleles determine the proinflammatory potential of serum IgA. AB - The human IgA FcR (FcalphaRI; CD89) mediates a variety of immune system functions including degranulation, endocytosis, phagocytosis, cytokine synthesis, and cytokine release. We have identified a common, nonsynonymous, single nucleotide polymorphism (SNP) in the coding region of CD89 (844A-->G) (rs16986050), which changes codon 248 from AGC (Ser(248)) to GGC (Gly(248)) in the cytoplasmic domain of the receptor. The two different alleles demonstrate significantly different FcalphaRI-mediated intracellular calcium mobilization and degranulation in rat basophilic leukemia cells and cytokine production (IL-6 and TNF-alpha) in murine macrophage P388D1 cells. In the absence of FcR gamma-chain association in P388D1 cells, the Ser(248)-FcalphaRI allele does not mediate cytokine production, but the Gly(248)-FcalphaRI allele retains the capacity to mediate a robust production of proinflammatory cytokine. This allele-dependent difference is also seen with FcalphaRI-mediated IL-6 cytokine release by human neutrophils ex vivo. These findings and the enrichment of the proinflammatory Gly(248)-FcalphaRI allele in systemic lupus erythematosus populations in two ethnic groups compared with their respective non-systemic lupus erythematosus controls suggest that FcalphaRI (CD89) alpha-chain alleles may affect receptor-mediated signaling and play an important role in the modulation of immune responses in inflammatory diseases. PMID- 17339499 TI - Human CD4+CD25low adaptive T regulatory cells suppress delayed-type hypersensitivity during transplant tolerance. AB - Adaptive T regulatory (T(R)) cells mediate the suppression of donor-specific, delayed-type hypersensitivity (DTH) in tolerant organ transplant recipients. We hypothesized that cells belonging to the CD4(+)CD25(+) T cell subset but distinct from natural T(R) cells may fulfill this role. To test this hypothesis, PBMC and biopsy samples from two tolerant kidney transplant recipients (K1 and K2) were analyzed. When transferred with recipient APC into a SCID mouse footpad, CD4(+) T cells were hyporesponsive in DTH to donor type HLA-B Ags and derivative allopeptides. However, anti-human TGF-beta1 Ab revealed a response to immunodominant allopeptides in both patients, suggesting that CD4(+) T effector (T(E)) cells coexisted with suppressive, TGF-beta1-producing CD4(+) T(R) cells. During in vitro culture, allopeptide stimulation induced both IFN-gamma-producing and surface TGF-beta1(+) T cells. The relative strength of the latter response in patient K1 was inversely correlated with the level of systemic anti-donor DTH, which varied over a 6-year interval. Allopeptide-induced surface TGF-beta1 expression was found primarily in Forkhead box P3 (FoxP3)-negative CD4(+)CD25(low) T cells, which could adoptively transfer suppression of donor specific DTH. Biopsy samples contained numerous surface TGF-beta1(+) mononuclear cells that costained for CD4 and, less frequently CD25, but were negative for FoxP3. The CD4(+)TGF-beta1(+) T cells were localized primarily to the tubulointerstitium, whereas TGF-beta1(-)FoxP3(+)CD25(+) cells were found mainly in lymphoid aggregates. Thus, adaptive T(R) cells suppressing T(E) cell responses to donor allopeptides in two tolerant patients appear to be functionally and phenotypically distinct from CD4(+)CD25(high)FoxP3(+) T cells. PMID- 17339500 TI - Effect of intermittent high-intensity compared with continuous moderate exercise on glucose production and utilization in individuals with type 1 diabetes. AB - Previously, the decline in glycemia in individuals with type 1 diabetes has been shown to be less with intermittent high-intensity exercise (IHE) compared with continuous moderate-intensity exercise (MOD) despite the performance of a greater amount of total work. The purpose of the present study was to determine whether this lesser decline in glycemia can be attributed to a greater increment in endogenous glucose production (Ra) or attenuated glucose utilization (Rd). Nine individuals with type 1 diabetes were tested on two separate occasions, during which either a 30-min MOD or IHE protocol was performed under conditions of a euglycemic clamp in combination with the infusion of [6,6-(2)H]glucose. MOD consisted of continuous cycling at 40% VO2 peak, whereas IHE involved a combination of continuous exercise at 40% VO2 peak interspersed with additional 4 s maximal sprint efforts performed every 2 min to simulate the activity patterns of intermittent sports. During IHE, glucose Ra increased earlier and to a greater extent compared with MOD. Similarly, glucose Rd increased sooner during IHE, but the increase by the end of exercise was comparable with that elicited by MOD. During early recovery from IHE, Rd rapidly declined, whereas it remained elevated after MOD, a finding consistent with a lower glucose infusion rate during early recovery from IHE compared with MOD (P<0.05). The results suggest that the lesser decline in glycemia with IHE may be attributed to a greater increment in Ra during exercise and attenuated Rd during exercise and early recovery. PMID- 17339501 TI - Bariatric surgery in adolescents: recent national trends in use and in-hospital outcome. AB - OBJECTIVES: To analyze recent nationwide trends in the use of adolescent bariatric surgery and to compare early postoperative outcomes of adolescents and adults undergoing these procedures. DESIGN: Analysis of national administrative data by using survey analysis techniques. SETTING: Data obtained from the Nationwide Inpatient Sample from 1996 to 2003. PARTICIPANTS: Adolescents (aged <20 years) and adults undergoing bariatric surgery. Intervention Bariatric surgery. MAIN OUTCOME MEASURES: Population-based case rates, major postoperative complications, length of hospital stay, hospital charges, and mortality. RESULTS: The population-based annual adolescent bariatric case volume varied little between 1996 and 2000 but more than tripled from 2000 to 2003. Despite this trend, only 771 bariatric procedures were performed in adolescents in 2003, representing fewer than 0.7% of bariatric procedures performed nationwide. Univariate comparison with data from 2003 showed a similar in-hospital complication rate in adolescents and adults but a significantly shorter length of stay among adolescents. Although in-hospital mortality was observed in 0.2% of adults, no in-hospital deaths were observed in any adolescents. CONCLUSIONS: Although procedure rates have increased recently, bariatric surgery in adolescents remains an uncommonly performed procedure. These data support efforts to align bariatric surgery programs for adolescents initially with higher volume programs for adults and to develop multicenter collaborative studies directed at defining the short- and long-term effect of bariatric surgery in morbidly obese adolescents. PMID- 17339502 TI - The prevalence and health care use of overweight children in an integrated health care system. AB - OBJECTIVE: To determine the prevalence, health care use, and costs of overweight children when compared with healthy-weight children. DESIGN: Longitudinal cohort. SETTING: Kaiser Permanente Colorado is an integrated, nonprofit health care system. Patients Eleven thousand six hundred thirty-six children who completed at least 1 body mass index (calculated as weight in kilograms divided by height in meters squared) assessment between 2000 and 2004. MAIN EXPOSURE: Overweight. MAIN OUTCOME MEASURE: Health care use. Based on previous research that demonstrated a higher cost for obese adults when compared with healthy-weight adults, we hypothesized that, when compared with healthy-weight children, overweight children would have higher health care use patterns. RESULTS: Thirteen percent and 14% of the sample, respectively, were classified as overweight or at risk of becoming overweight. At both year 1 (rate ratio [RR] = 1.11 [95% confidence interval (CI), 1.06-1.17]) and year 3 (RR = 1.06 [95% CI, 1.01-1.11]), overweight children had significantly more internal Kaiser Permanente Colorado medical visits, although the magnitude of the relationship was relatively small. Of particular note was the relationship between being overweight and increased use of mental health resources at both points (year 1 RR = 1.47; year 3 RR = 1.48). The calculated additional annual cost of use for 1000 overweight children (regression adjusted to control for comorbidities) was approximately $42 000 for primary care sick visits and $32 000 for mental health visits. CONCLUSION: There is potential for cost savings or cost realignment with weight-management interventions from dollars that could be saved through the reduction of childhood overweight. PMID- 17339503 TI - Association of family stress with natural killer cell activity and the frequency of illnesses in children. AB - OBJECTIVE: To examine prospective associations between chronic stress in the parent-child and family systems and subsequent rates of illnesses and the activity of natural killer (NK) cells in children. DESIGN: Prospective cohort study. SETTING: The Golisano Children's Hospital at Strong, Rochester, NY, from July 1, 2001, to June 30, 2003. PARTICIPANTS: One hundred sixty-nine socioeconomically and racially diverse children (aged 5-10 years) and their parents. Parents completed measures of their psychiatric symptoms and stress in the family every 6 months. Children's blood samples were obtained for NK cytotoxicity assays every 6 months. MAIN OUTCOME MEASURES: Parent-reported total child illnesses and febrile illnesses and results of NK cell cytotoxicity assays. We estimated adjusted illness rate ratios and adjusted mean differences in NK activity. RESULTS: Elevated parental psychiatric symptoms occurring with family stressors were associated with more total illnesses (rate ratio, 1.11; 95% confidence interval [CI], 1.00-1.22) and febrile illnesses (rate ratio, 1.36; 95% CI, 1.13-1.64) in children. Natural killer cell function was enhanced in children whose parents reported more chronic stress (estimate, 0.15; 95% CI, 0.05-0.26). Natural killer cell function was not associated with short-term changes in stress. Stress-illness relationships were not associated with stress-related alterations in NK cell function. CONCLUSIONS: Chronic family stress was associated with increased illnesses in children. Unlike older adults, children living with elevated chronic stress had enhanced rather than decreased NK cytotoxicity, suggesting chronic stress may have different effects on the developing immune system. Impaired parental functioning may be a mechanism linking family stress with adverse effects on children's health. PMID- 17339504 TI - Benefits and harms associated with the practice of bed sharing: a systematic review. AB - OBJECTIVE: To examine evidence of benefits and harms to children associated with bed sharing, factors (eg, smoking) altering bed sharing risk, and effective strategies for reducing harms associated with bed sharing. DATA SOURCES: MEDLINE, CINAHL, Healthstar, PsycINFO, the Cochrane Library, Turning Research Into Practice, and Allied and Alternative Medicine databases between January 1993 and January 2005. STUDY SELECTION: Published, English-language records investigating the practice of bed sharing (defined as a child sharing a sleep surface with another individual) and associated benefits and harms in children 0 to 2 years of age. DATA EXTRACTION: Any reported benefits or harms (risk factors) associated with the practice of bed sharing. DATA SYNTHESIS: Forty observational studies met our inclusion criteria. Evidence consistently suggests that there may be an association between bed sharing and sudden infant death syndrome (SIDS) among smokers (however defined), but the evidence is not as consistent among nonsmokers. This does not mean that no association between bed sharing and SIDS exists among nonsmokers, but that existing data do not convincingly establish such an association. Data also suggest that bed sharing may be more strongly associated with SIDS in younger infants. A positive association between bed sharing and breastfeeding was identified. Current data could not establish causality. It is possible that women who are most likely to practice prolonged breastfeeding also prefer to bed share. CONCLUSION: Well-designed, hypothesis driven prospective cohort studies are warranted to improve our understanding of the mechanisms underlying the relationship between bed sharing, its benefits, and its harms. PMID- 17339505 TI - Burden of recurrent Chlamydia trachomatis infections in young women: further uncovering the "hidden epidemic". AB - OBJECTIVE: To determine the frequency and patterns of recurrent Chlamydia trachomatis infections, the most common bacterial sexually transmitted infection in young women. DESIGN: Cohort study using different data collection methods, including face-to-face interviews, medical record reviews, urine-based screening for C trachomatis infections, and a review of state health department reports of C trachomatis diagnoses. SETTING: Ten community-based health centers that provided reproductive health care from June 1998 to September 2001. PARTICIPANTS: Eligibility criteria included being nulliparous, between the ages of 14 and 19 years, and human immunodeficiency virus-negative, all at the time of recruitment. This convenience sample (N = 411) was recruited by word of mouth, clinician referrals, and advertisements in the clinics. Prospective follow-up data were available for 93.9% (386/411) of the sample. The exposure of interest was prior chlamydia infection. Main Outcome Measure Diagnosis of recurrent C trachomatis infection. RESULTS: During the follow-up period of 23 318 person-months (mean, 4.7 years per person), 216 participants (52.6%) were diagnosed as having C trachomatis infection, and 123 participants (29.9% of the total sample and 56.9% of those with initial infections) were diagnosed as having recurrent C trachomatis infections. Of 456 C trachomatis diagnoses made during the study period, 241 (52.9%) were recurrent infections. The rate of recurrent infections was 42.1 per 1000 person-months. The median time to recurrent infection was 5.2 months. CONCLUSION: Recurrent C trachomatis infections comprise a substantial health burden among young women, possibly higher than previously recognized in this vulnerable population. PMID- 17339506 TI - National health care visit patterns of adolescents: implications for delivery of new adolescent vaccines. AB - OBJECTIVE: To prepare for new adolescent vaccinations by examining current use of adolescent outpatient health care visits throughout the United States. DESIGN: Cross-sectional analysis of visits. SETTING: Outpatient hospital- and office based practices in the United States included in the 1994-2003 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey. PARTICIPANTS: Adolescents ages 11 to 21 years (n = 63 529) with outpatient visits. MAIN OUTCOME MEASURES: Type of physician seen for overall and preventive visits, visit trends over time, demographics of adolescents seen by pediatricians vs family physicians, and visit type during which a vaccine was provided. RESULTS: Late-adolescence females (18-21 years old) had the most overall visits, 36% of which were to obstetrician-gynecologists. Pediatricians were seen at most outpatient visits for adolescents 14 years or younger, with fewer visits for those older than 14 years. Family practitioners were seen at one quarter of all outpatient visits. Only 9% of all adolescent visits were for preventive care. Early adolescents (11-14 years old) had 3 times more preventive visits than late adolescents (P<.001). Pediatricians were more likely to see adolescents who were younger, male, black, and urban and were more likely to be seen for preventive visits compared with family physicians (P<.001 for all). Altogether, 80%, 70%, and 64% of visits that included measles-mumps-rubella, hepatitis B, and diphtheria-tetanus vaccinations, respectively, were for preventive care. CONCLUSIONS: On the basis of current utilization patterns, adolescent vaccinations should be delivered during early or middle adolescence. If vaccines are to be provided to older adolescent females, involvement of obstetrician-gynecologists in vaccine delivery is critical. PMID- 17339507 TI - R-rated movies, bedroom televisions, and initiation of smoking by white and black adolescents. AB - OBJECTIVE: To test movie exposure and television use as predictors of smoking initiation among white and black adolescents who had never smoked cigarettes. DESIGN: Survey research using audio computer-assisted self-interviews at baseline and at 2-year follow-up (2002-2004). SETTING: Participants' homes located in central North Carolina. PARTICIPANTS: A sample of 735 12- to 14-year-old adolescents drawn from 14 public middle schools. MAIN EXPOSURE: Frequency of exposure to movies rated R, PG-13, PG, or G; frequency, location, and parental oversight of television viewing. MAIN OUTCOME MEASURE: Initiation of smoking, indicated by the first occasion of puffing on a cigarette. RESULTS: Among white adolescents, high relative exposure to R-rated movies predicted a significantly greater likelihood of smoking initiation at follow-up, and private access to television during early adolescence, indicated by having a bedroom television, was also a significant independent predictor of smoking initiation at follow-up. No significant associations were observed between any movie-exposure or television-use variables and likelihood of smoking among black adolescents. CONCLUSIONS: Indicators of risky media use were associated with a significantly greater likelihood of smoking for white but not for black adolescents. These results diverge strongly from past results, which have indicated that all adolescents, regardless of race or place of residence, have a higher risk of smoking initiation as their exposure to movie smoking increases. Research is needed to identify the antecedents of risky media use and to understand how audience attributes, including race and other factors, moderate the effects of risky media use on health-related behaviors. PMID- 17339508 TI - Effect of booster seat laws on appropriate restraint use by children 4 to 7 years old involved in crashes. AB - OBJECTIVE: To quantify the independent contribution of recently enacted booster seat laws on appropriate restraint use by child passengers in motor vehicles. DESIGN: Longitudinal study of children involved in crashes with data collected via insurance claims records and a validated telephone survey. SETTING: Sixteen states and Washington, DC, from December 1, 1998, through December 31, 2004. PARTICIPANTS: Probability sample of 5198 vehicles in crashes involving 6102 children aged 4 to 7 years, representing 78 159 vehicles and 91 752 children. MAIN EXPOSURES: Booster seat law provisions, child age, state, and secular trends. MAIN OUTCOME MEASURE: Reported appropriate restraint use for this age group, including forward-facing child safety seats, belt-positioning booster seats, and combination seats. RESULTS: Children aged 4 to 7 years in states with booster seat laws were 39% more likely to be reported as appropriately restrained than were children in other states (prevalence ratio [PR], 1.39; 95% confidence interval [CI], 1.14-1.70). Children aged 4 to 5 years were 23% more likely (PR,1.23; 95% CI, 0.80-1.42) and children 6 to 7 years twice as likely (PR, 2.09; 95% CI, 1.46-2.99) to be reported as appropriately restrained. For children aged 6 to 7 years, when compared with no law, laws through age 7 years were most effective (PR, 3.71; 95% CI, 2.49-5.42), followed by laws through age 4 or 5 years (PR, 1.43; 95% CI, 0.89-2.24). CONCLUSION: Given the higher current use of age-appropriate restraints among children 4 to 5 years compared with older children, future upgrades to child restraint laws should include children through at least age 7 years to maximize the number of children properly restrained for their age. PMID- 17339509 TI - Prescription drug abuse and diversion among adolescents in a southeast Michigan school district. AB - OBJECTIVES: To determine the prevalence of medical use of 4 classes of prescription medications relative to nonmedical use (illicit use), to examine the relative rates among the 4 drug classes, and to assess whether gender differences exist in the trading, selling, loaning, or giving away of medications. DESIGN: A Web-based survey was administered to 7th- to 12th-grade students residing in 1 ethnically diverse school district; a 68% response rate was achieved. SETTING: During a 3-week period in May 2005, teachers brought students to their schools' computing center where students took the survey using a unique personal identification number to sign on to the survey. PARTICIPANTS: There were 1086 secondary students, including 586 girls, 498 boys, 484 black students, and 565 white students. MAIN OUTCOME MEASURES: Students were asked about their medical and nonmedical use of sleeping, sedative or anxiety, stimulant, and pain medications. Diversion of prescription medication was assessed by determining who asked the student to divert his or her prescription and who received it. RESULTS: Thirty-six percent of students reported having a recent prescription for 1 of the 4 drug classes. A higher percentage of girls reported giving away their medications than boys (27.5% vs 17.4%, respectively; chi(2)(1) = 6.7; P = .01); girls were significantly more likely than boys to divert to female friends (64.0% vs 21.2%, respectively; chi(2)(1) = 17.5; P<.001) whereas boys were more likely than girls to divert to male friends (45.5% vs 25.6%, respectively; chi(2)(1) = 4.4; P = .04). Ten percent diverted their drugs to parents. CONCLUSION: Physicians should discuss the proper use of prescription medications with their patients and their patients' families. PMID- 17339510 TI - Off-label drug use in hospitalized children. AB - OBJECTIVES: To describe the magnitude of off-label drug use, to identify drugs most commonly used off-label, and to identify factors associated with off-label drug use in children hospitalized in the United States. DESIGN: Retrospective cohort study. SETTING: Administrative database containing inpatient resource utilization data from January 1 to December 31, 2004, from 31 tertiary care pediatric hospitals in the United States. PARTICIPANTS: Hospitalized patients 18 years or younger. MAIN EXPOSURES: Institution and patient characteristics. MAIN OUTCOME MEASURES: Off-label drug use was defined as use of a specific drug in a patient younger than the Food and Drug Administration-approved age range for any indication of that drug. RESULTS: At least 1 drug was used off-label in 297 592 (78.7%) of 355 409 patients discharged during the study. Off-label use accounted for $270 275 849 (40.5%) of the total dollars spent on these medications. Medications classified as central or autonomic nervous system agents or as fluids or nutrients, or gastrointestinal tract agents were most commonly used off-label, whereas antineoplastic agents were rarely used off-label. Factors associated with off-label use in multivariate analysis were as follows: undergoing a surgical procedure, age older than 28 days, greater severity of illness, and all-cause in hospital mortality. CONCLUSIONS: Most patients hospitalized at tertiary care pediatric institutions receive at least 1 medication outside the terms of the Food and Drug Administration product license. Substantial variation in the frequency of off-label use was observed across diagnostic categories and drug classes. Despite the frequent off-label use of drugs, using an administrative database, we cannot determine which of these treatments are unsafe or ineffective and which treatments result in substantial benefit to the patient. PMID- 17339511 TI - Persistence of measles antibodies after 2 doses of measles vaccine in a postelimination environment. AB - OBJECTIVE: To evaluate the persistence of measles antibodies after 2 doses of measles vaccine in a setting where exposure to wild-type measles was unlikely. Measles was declared eliminated from the United States in 2000, an achievement attributed to effective implementation of a routine 2-dose vaccination policy. Some have questioned whether measles transmission could resume if immunity wanes in the absence of boosting from wild-type measles. DESIGN: Prospective, observational, volunteer cohort study. SETTING: Rural Wisconsin health maintenance organization. PARTICIPANTS: Children who received the second measles vaccine dose at kindergarten (aged 4-6 years) or middle school (aged 10-12 years) in 1994 or 1995. Serum samples were collected periodically during a 10-year period for the kindergarten group and a 5-year period for the middle school group. INTERVENTION: Second dose of measles vaccine. MAIN OUTCOME MEASURE: Measles antibody levels were assessed by plaque-reduction neutralization: titers less than 8 mIU/mL were considered seronegative and suggestive of susceptibility to measles, and titers of 120 mIU/mL or less were considered low and suggestive of potential susceptibility. RESULTS: During the study period, no measles was reported in the study area. Voluntary attrition reduced the study population from 621 at enrollment to 364 (58.6%) by study end. Before the second dose, 3.1% (19/621) had low titers, of whom 74% (14/19) were antibody-negative, with geometric mean titers being significantly higher in kindergarteners (1559 mIU/mL) than in middle schoolers (757 mIU/mL) and rates of negativity significantly lower (1.0% [3/312] vs 3.6% [11/309]). One month after the second dose, 0.2% (1/612) had low titers and none was seronegative, with geometric mean titers being significantly higher in kindergarteners (2814 mIU/mL) than in middle schoolers (1672 mIU/mL). By study end, 4.9% (18/364) had low titers and none was seronegative, with no significant difference in geometric mean titers between kindergarteners (641 mIU/mL) and middle schoolers (737 mIU/mL) when both groups were aged 15 years. Projections suggest that the proportion of persons with low antibody levels may increase over time. CONCLUSIONS: Measles antibody persisted in all vaccinees available for follow-up 10 years after a second dose of vaccine, with no seronegative results detected. Declining titers suggest the need for vigilance in ensuring disease protection for the vaccinated population. PMID- 17339512 TI - Picture of the month. Severe skin ulceration after tuberculin skin test. PMID- 17339513 TI - Sudden infant death syndrome: should bed sharing be discouraged? PMID- 17339514 TI - The Agnew Clinic. PMID- 17339515 TI - Science and torture. PMID- 17339516 TI - Torture vs other cruel, inhuman, and degrading treatment: is the distinction real or apparent? AB - CONTEXT: After the reports of human rights abuses by the US military in Guantanamo Bay, Iraq, and Afghanistan, questions have been raised as to whether certain detention and interrogation procedures amount to torture. OBJECTIVE: To examine the distinction between various forms of ill treatment and torture during captivity in terms of their relative psychological impact. DESIGN AND SETTING: A cross-sectional survey was conducted with a population-based sample of survivors of torture from Sarajevo in Bosnia and Herzegovina, Banja Luka in Republica Srpska, Rijeka in Croatia, and Belgrade in Serbia. PARTICIPANTS: A total of 279 survivors of torture accessed through linkage sampling in the community (Banja Luka, Sarajevo, and Rijeka) and among the members of 2 associations for war veterans and prisoners of war (Belgrade). MAIN OUTCOME MEASURES: Scores on the Semi-structured Interview for Survivors of War, Exposure to Torture Scale, Structured Clinical Interview for DSM-IV, and Clinician-Administered PTSD (posttraumatic stress disorder) Scale for DSM-IV. RESULTS: Psychological manipulations, humiliating treatment, exposure to aversive environmental conditions, and forced stress positions showed considerable overlap with physical torture stressors in terms of associated distress and uncontrollability. In regression analyses, physical torture did not significantly relate to posttraumatic stress disorder (odds ratio, 1.41, 95% confidence interval, 0.89 2.25) or depression (odds ratio, 1.41, 95% confidence interval, 0.71-2.78). The traumatic stress impact of torture (physical or nonphysical torture and ill treatment) seemed to be determined by perceived uncontrollability and distress associated with the stressors. CONCLUSIONS: Ill treatment during captivity, such as psychological manipulations, humiliating treatment, and forced stress positions, does not seem to be substantially different from physical torture in terms of the severity of mental suffering they cause, the underlying mechanism of traumatic stress, and their long-term psychological outcome. Thus, these procedures do amount to torture, thereby lending support to their prohibition by international law. PMID- 17339517 TI - Relationship of imprecise corollary discharge in schizophrenia to auditory hallucinations. AB - CONTEXT: A forward model of intended thoughts and actions prepares sensory cortex for sensations that are a consequence of those actions. Imprecision of the corollary discharge in schizophrenia may contribute to the misperception of inner experiences and thoughts as "voices" or auditory hallucinations. OBJECTIVES: To assess the precision of the forward model in schizophrenia using the N100 component of the auditory event-related potential to speech that is altered or unaltered, in real time, as it is being spoken. To assess the relationship between auditory hallucinations and the imprecision of the corollary discharge. DESIGN: Prospective case-control study. SETTING: Community mental health centers and Palo Alto Veterans Affairs Health Care System, Palo Alto, Calif. PARTICIPANTS: Twenty patients with schizophrenia and 17 sex- and age-matched healthy control subjects. MAIN OUTCOME MEASURES: N100 responses to auditory feedback, which was altered by pitch-shifting the self-voice, substituting an alien voice, or pitch-shifting the alien voice. On each trial, subjects judged whether feedback was "self," "other," or "unsure." Clinical ratings were used to assess severity of auditory hallucinations in patients. RESULTS: In controls, N100 to unaltered self-voice feedback was dampened relative to N100 to altered self-voice or alien auditory feedback. This pattern was not seen in hallucinating patients. This imprecision correlated with the severity of hallucinations and with the percentage of misattribution errors. CONCLUSION: These data support a connection between auditory verbal hallucinations and the imprecision of the corollary discharge heralding the sensory consequences of thoughts and actions. PMID- 17339518 TI - Brain volumes in relatives of patients with schizophrenia: a meta-analysis. AB - CONTEXT: Smaller brain volumes have consistently been found in patients with schizophrenia, particularly in gray matter and medial temporal lobe structures. Although several studies have investigated brain volumes in nonpsychotic relatives of patients with schizophrenia, results have been inconsistent. OBJECTIVE: To determine the magnitude and extent of brain volume differences in first-degree relatives of schizophrenic patients. DATA SOURCES: A systematic search was conducted to identify relevant studies. Computer searches of the MEDLINE database were performed for English-language articles published before July 2005. Relevant abstracts published in 2005 were also selected. STUDY SELECTION: Magnetic resonance imaging studies that examined differences in brain volumes between first-degree relatives of patients with schizophrenia and healthy control subjects were obtained through computerized databases, including MEDLINE. Studies had to report sufficient data for computation of effect sizes. DATA EXTRACTION: For each study, the Cohen d was calculated. Data extraction and calculation of the effect size were performed by 2 authors (H.B.M.B. and A.A.) who reached a consensus in cases of uncertainty and discrepancies. All analyses were performed using the random-effects model. DATA SYNTHESIS: Twenty-five studies were identified as suitable for analysis and included 1065 independent first-degree relatives of patients, 679 patients with schizophrenia, and 1100 healthy control subjects. The largest difference between relatives and healthy control subjects was found in hippocampal volume, with relatives having smaller volumes than controls (d = 0.31; 95% confidence interval [CI], 0.13-0.49; 9 effect sizes). Gray matter was smaller (d = 0.18; 95% CI, 0.02-0.33; 7 effect sizes) and third-ventricle volume was larger (d = 0.21; 95% CI, 0.03-0.40; 7 effect sizes) in relatives compared with healthy control subjects. CONCLUSION: Brain abnormalities are present in nonpsychotic first-degree relatives of patients with schizophrenia and are most pronounced in the hippocampus. PMID- 17339519 TI - Prevalence and distribution of major depressive disorder in African Americans, Caribbean blacks, and non-Hispanic whites: results from the National Survey of American Life. AB - CONTEXT: Little is known about the relationship between race/ethnicity and depression among US blacks. OBJECTIVE: To estimate the prevalence, persistence, treatment, and disability of depression in African Americans, Caribbean blacks, and non-Hispanic whites in the National Survey of American Life. DESIGN: A slightly modified adaptation of the World Health Organization World Mental Health version of the Composite International Diagnostic Interview. SETTING: National household probability samples of noninstitutionalized African Americans, Caribbean blacks, and non-Hispanic whites in the United States conducted between February 2, 2001, and June 30, 2003. PARTICIPANTS: A total of 3570 African Americans, 1621 Caribbean blacks, and 891 non-Hispanic whites aged 18 years and older (N = 6082). MAIN OUTCOME MEASURES: Lifetime and 12-month diagnoses of DSM IV major depressive disorder (MDD), 12-month mental health services use, and MDD disability as quantified using the Sheehan Disability Scale and the World Health Organization's Disability Assessment Schedule II. RESULTS: Lifetime MDD prevalence estimates were highest for whites (17.9%), followed by Caribbean blacks (12.9%) and African Americans (10.4%); however, 12-month MDD estimates across groups were similar. The chronicity of MDD was higher for both black groups (56.5% for African Americans and 56.0% for Caribbean blacks) than for whites (38.6%). Fewer than half of the African Americans (45.0%) and fewer than a quarter (24.3%) of the Caribbean blacks who met the criteria received any form of MDD therapy. In addition, relative to whites, both black groups were more likely to rate their MDD as severe or very severe and more disabling. CONCLUSIONS: When MDD affects African Americans and Caribbean blacks, it is usually untreated and is more severe and disabling compared with that in non-Hispanic whites. The burden of mental disorders, especially depressive disorders, may be higher among US blacks than in US whites. PMID- 17339520 TI - Anxiety and comorbid measures associated with PLXNA2. AB - CONTEXT: Reduction in adult neurogenesis has been proposed as a mechanism for onset of depression. Semaphorins and their coreceptors, plexins, have been implicated in nervous system development and in adult neurogenesis. A recent genomewide association study of schizophrenia identified a variant of the gene encoding plexin A2 (PLXNA2) to be most consistently associated across study samples. Common genetic liabilities have been reported between psychiatric and psychological measures, but few examples exist of common genetic variants. OBJECTIVE: To perform a genetic association study between 6 single nucleotide polymorphisms from the PLXNA2 gene (rs3736963, rs2767565, rs752016, rs1327175, rs2478813, and rs716461) and anxiety, depression, neuroticism, and psychological distress. DESIGN: Extreme discordant and concordant siblings. SETTING: Australia. PARTICIPANTS: Study participants were selected with respect to extreme neuroticism scores from a population cohort of 18 742 twin individuals and their siblings. The participants and their parents (if blood or buccal samples were available) were genotyped, for a total of 2854 genotyped individuals from 990 families. Of these, 624 individuals with a diagnosis of anxiety or depression from 443 families were used in the association analysis. MAIN OUTCOME MEASURES: All the participants completed the Composite International Diagnostic Interview, the 23-item Neuroticism scale of the revised Eysenck Personality Questionnaire, and the 10-item Kessler Psychological Distress Scale. Diagnoses of DSM-IV depression and anxiety were determined from the Composite International Diagnostic Interview. RESULTS: There was evidence of an allelic association between rs2478813 (and other single nucleotide polymorphisms correlated with it) and anxiety, depression, neuroticism, and psychological distress; the association with anxiety is significant after Bonferroni correction for multiple testing (empirical P<.001). The mouse ortholog of PLXNA2 is located in a highly significant linkage region previously reported for anxiety in mice. CONCLUSION: PLXNA2 is a candidate for causal variation in anxiety and in other psychiatric disorders through its comorbidity with anxiety. PMID- 17339521 TI - The role of dopamine in the pathophysiology of depression. PMID- 17339522 TI - Prediction from low birth weight to female adolescent depression: a test of competing hypotheses. AB - CONTEXT: Low birth weight (LBW) predicts later-onset hypertension and diabetes mellitus. Its role as a predictor of depression is unclear. OBJECTIVES: To examine whether LBW predicts depression in male and female children and adolescents and to compare the following 2 hypotheses: Low birth weight is one among several perinatal, childhood, and adolescent risk factors for depression (biopsychosocial hypothesis). Low birth weight is a marker for poor intrauterine conditions that provoke adjustments in fetal development, with long-term consequences for stress response (fetal programming hypothesis). DESIGN: A representative population-based sample from an 11-county area in western North Carolina was assessed annually for psychiatric disorders between the ages of 9 and 16 years. We tested the prediction from LBW and depression in models that included LBW only, LBW plus other prenatal and perinatal adversities, LBW plus significant perinatal and childhood adversities, and LBW plus significant perinatal and childhood adversities and adolescent correlates. SETTING: Academic research. PARTICIPANTS: There were 1420 participants, of whom 49% were female. Main Outcome Measure Cumulative prevalence of DSM-IV depressive disorder at 1 assessment or more during childhood (age range, 9-12 years) and during adolescence (age range, 13-16 years). RESULTS: The cumulative prevalence of depression among adolescent girls with LBW was 38.1% (95% confidence interval [CI], 16.3%-66.0%) compared with 8.4% (95% CI, 5.2%-13.3%) among adolescent girls with normal birth weight. Rates among children and adolescent boys did not exceed 4.9%. In adolescence, there was a significant interaction between LBW and sex (odds ratio, 0.2 [95% CI, 0.1-0.5]; P<.001). Low birth weight predicted female adolescent depression after controlling for other perinatal, childhood, and adolescent adversities. Girls with LBW and normal birth weight with no adversities had no adolescent depression, but each additional adversity increased the risk of in girls with LBW more than in girls with normal birth weight. Low birth weight did not predict other psychiatric disorders in either sex. CONCLUSIONS: Low birth weight predicts depression in adolescent girls but not boys. Data support fetal programming over the biopsychosocial hypothesis, suggesting vulnerability to adversities in girls with LBW after puberty. PMID- 17339523 TI - Death by unnatural causes during childhood and early adulthood in offspring of psychiatric inpatients. AB - CONTEXT: Offspring of psychiatric inpatients are at higher risk of death from all causes, but their cause-specific risks have not been quantified. OBJECTIVE: To investigate cause-specific deaths at 1 to 25 years in offspring of parents previously admitted as psychiatric inpatients. DESIGN: Population-based cohort study. SETTING: The entire Danish population. PARTICIPANTS: All singleton births (N = 1.38 million) from January 1, 1973, to December 31, 1997, with follow-up to January 1, 1999. Linkage to the national psychiatric register identified all previous parental admissions. MAIN OUTCOME MEASURES: Deaths from all natural causes and all unnatural causes, specifically, accidents, homicides, suicides, and undetermined causes. RESULTS: The highest observed relative risk (RR) was for homicide in young and older children with affected mothers or fathers. Homicides were between 5 and 10 times more likely to occur in this group, according to child's age and whether the mother or father had been admitted. There was previous parental admission in approximately one third of all child homicides. We found no evidence of increased risk of homicide in exposed young adults, but this group had a 2-fold to 3-fold higher risk of suicide. In almost one fourth of the suicides, there was a history of parental admission. Young adults with 2 previously admitted parents were 6 times more likely to kill themselves than were their peers in the general population. Relative risk of suicide or open-verdict deaths by poisoning were higher than for such deaths occurring by other means. CONCLUSIONS: Almost 99% of children studied survived to their mid-20s. However, they were more vulnerable to death from unnatural causes, notably, homicide during childhood and suicide in early adulthood. Further research is needed to establish how parental psychopathology contributes to increased risk of premature death in these offspring. PMID- 17339524 TI - Serotonin receptor 2A gene and the influence of childhood maternal nurturance on adulthood depressive symptoms. AB - BACKGROUND: Gene-environment interactions are assumed to be involved in the development of depression. OBJECTIVE: To determine whether the serotonin receptor 2A (HTR2A) gene moderates the association between childhood maternal nurturance and depressive symptoms in adulthood. DESIGN: A 21-year, prospective, longitudinal study with 2 measurements of the independent and dependent variables. SETTING: A population-based sample. PARTICIPANTS: A subsample of 1212 participants of the Cardiovascular Risk in Young Finns study, aged 3 to 18 years at baseline. Main Outcome Measure Depressive symptoms in adulthood. RESULTS: Individuals carrying the T/T or T/C genotype of the T102C polymorphism of the HTR2A gene were responsive to the protective aspects of nurturing mothering, so that in the presence of high maternal nurturance, they expressed low levels of depressive symptoms, while this was not true with the carriers of the C/C genotype. CONCLUSION: The HTR2A gene may be involved in the development of depression by influencing the ability of individuals to use environmental support. PMID- 17339525 TI - Pretrauma cognitive ability and risk for posttraumatic stress disorder: a twin study. AB - CONTEXT: Cognitive deficits are associated with posttraumatic stress disorder (PTSD), but whether such deficits reflect sequelae or risk factors is not fully resolved. OBJECTIVE: To determine, in a representative sample, whether preexposure cognitive ability is associated with risk for PTSD, and whether that risk is genetically mediated. DESIGN, SETTING, AND PARTICIPANTS: The co-twin control study involved 2386 male Vietnam-era twin veterans with a mean (SD) age of 41.9 (2.7) years, a population-based sample of men who were in military service during this era. Cognitive ability scores were obtained just before military induction at a mean (SD) age of 19.7 (1.5) years. Participants included only individuals who were exposed to potentially traumatic events and underwent preexposure cognitive testing. MAIN OUTCOME MEASURES: Armed Forces Qualification Test (of cognitive ability) percentile scores and PTSD diagnosed by means of structured interviews. RESULTS: We found a significant dose-response relationship between preexposure cognitive ability and risk for PTSD. After controlling for confounders, the highest cognitive ability quartile had a 48% lower risk than the lowest ability quartile (P<.001). Non-PTSD-concordant pairs had the highest scores; PTSD-concordant pairs had the lowest scores; and PTSD-discordant pairs had intermediate scores. Differences in Armed Forces Qualification Test scores within twin pairs were significant only in PTSD-discordant pairs (P=.04) and were accounted for specifically by the discordant dizygotic pairs (P=.002). Genetic influences on preexposure cognitive ability explained 5% of the variation in PTSD, but 100% of that relationship was explained by common genes. CONCLUSIONS: Preexposure cognitive ability is a risk or a protective factor for PTSD. The variance in PTSD explained by preexposure cognitive ability is accounted for entirely by common genetic factors. Lower cognitive ability may be a marker of less adaptive coping against adverse mental health consequences of exposure to potentially traumatic events. Further study of the potential mechanisms through which cognitive ability confers risk is needed. PMID- 17339526 TI - Association of a functional polymorphism in the mu-opioid receptor gene with alcohol response and consumption in male rhesus macaques. AB - CONTEXT: Innate differences in opioid neurotransmission are hypothesized to influence abuse liability of alcohol. In humans, a variant of the mu-opioid receptor gene (OPRM1A118G) increases receptor affinity, alcohol-induced euphoria, and risk for alcohol use disorders. OBJECTIVE: To determine whether a variant in the mu-opioid receptor gene (OPRM1C77G) that increases affinity of the receptor is associated with alcohol response and consumption in macaques. DESIGN: Young adult rhesus macaques (Macaca mulatta) were intravenously administered 2.0 to 2.1 g of ethanol per kilogram of body weight and assessed for alcohol response. Animals were later given simultaneous access to an aspartame-sweetened 8.4% (vol/vol) ethanol solution and a vehicle for 1 hour per day, 5 days a week, for a period of 6 weeks. Animals (N = 82) were genotyped for the OPRM1C77G polymorphism; the effects of the genotype on alcohol response and consumption were determined by analysis of variance, with sex included as a nominal independent variable. MAIN OUTCOME MEASURES: Alcohol response (ataxia, stimulation, and sedation), average alcohol consumption, the percentage of days during which an animal consumed alcohol at a level sufficient to produce intoxication (> or =0.67 g of alcohol per kilogram of body weight), and alcohol preference (calculated as 100 x {alcoholic solution/[alcoholic solution + nonalcoholic solution]}). RESULTS: Increased alcohol-induced stimulation was observed among male macaques carrying the OPRM1C77G allele. OPRM1C77G allele carriers consumed more ethanol and exhibited increased ethanol preference. Male carriers of the OPRM1C77G allele exhibited higher alcohol preference and consumption, and drank to intoxication more frequently than did C/C males. CONCLUSIONS: These findings demonstrate that the rhesus macaques' equivalent of the OPRM1A118G variant is associated with increased alcohol response, consumption, and preference. Our results reveal effects of the OPRM1C77G genotype to be male-restricted or more marked among male macaques. This is of interest, given the fact that early-onset type II alcoholism is more common among men and that, among addicted individuals, men are more responsive to mu-opioid receptor blockade. PMID- 17339527 TI - Promoting measured genes and measured environments: on the importance of careful statistical analyses and biological relevance. PMID- 17339528 TI - Errors in assessing DSM-IV substance use disorders. PMID- 17339529 TI - Drug use disorders in the National Comorbidity Survey: have we come a long way? PMID- 17339530 TI - Stopping stress at its origins: addressing working conditions. PMID- 17339531 TI - Sympathetic hyperactivity in hypertensive chronic kidney disease patients is reduced during standard treatment. PMID- 17339532 TI - Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction. AB - Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil mediated NHE-1 inhibition. MI was induced by left anterior descending coronary artery ligation in Wistar rats, which were randomized to placebo or sildenafil (100 mg kg(-1) day(-1)) for 6 weeks. Sildenafil significantly increased left ventricular phosphoglycerate kinase-1 activity in the post-MI group without affecting its expression. MI increased heart weight/body weight ratio, left ventricular myocyte cross-sectional area, interstitial fibrosis, and brain natriuretic peptide and NHE-1 expression. Sildenafil blunted these effects. Neither a significant change in infarct size nor a change in arterial or left ventricular systolic pressure was detected after sildenafil. MI decreased fractional shortening and the ratio of the maximum rate of rise of LVP divided by the pressure at the moment such maximum occurs, effects that were prevented by sildenafil. Intracellular pH recovery after an acid load was faster in papillary muscles from post-MI hearts (versus sham), whereas sildenafil significantly inhibited NHE-1 activity in both post-MI and sildenafil-treated sham groups. We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction. PMID- 17339534 TI - Contribution of endothelial nitric oxide to blood pressure in humans. PMID- 17339535 TI - Molecular genetics of experimental hypertension and the metabolic syndrome: from gene pathways to new therapies. AB - Genetic studies of human and experimental hypertension provide a means to identify key pathways that predispose individuals to increased blood pressure and associated risk factors for cardiovascular and metabolic diseases. The pathways so identified can then serve as targets for therapeutic intervention. This article discusses genetic studies in animal models of hypertension in which specific genes have been identified that regulate blood pressure and biochemical features of the metabolic syndrome. Consistent with studies in humans with monogenic disorders of blood pressure regulation, studies in rat models have demonstrated that naturally occurring genetic variation in pathways regulating sodium chloride transport can contribute to inherited variation in blood pressure. Such studies have also indicated that naturally occurring variation in genes, such as Cd36, that regulate fatty acid metabolism and ectopic accumulation of fat and fat metabolites can influence both biochemical and hemodynamic features of the metabolic syndrome and mediate the antidiabetic effects of drugs that activate the peroxisome proliferator-activated receptor-gamma. Angiotensin II receptor blockers with the ability to selectively modulate activity of peroxisome proliferator-activated receptor-gamma and expression of genes in these fat metabolism pathways may represent useful prototypes for a new class of transcription modulating drugs aimed at treating patients with hypertension and the metabolic syndrome. PMID- 17339536 TI - Fos-related antigen immunoreactivity after acute and chronic angiotensin II induced hypertension in the rabbit brain. AB - Several brain regions are proposed as contributing to chronic sympatho-excitatory effects of elevated circulating angiotensin II. However, earlier c-Fos studies have been limited to acute angiotensin II exposure. This study aims to determine brain regions responding with chronic elevated angiotensin II. Rabbits were administered angiotensin II (50 ng/kg per minute) or saline for 3 hours, 3 days, or 14 days. Basal mean arterial pressure was 71+/-2 mm Hg and increased 23+/-2 mm Hg, 32+/-4 mm Hg, and 22+/-2 mm Hg for 3 hours, 3 days, and 14 days, respectively, with angiotensin II infusion. Neuronal activation was detected using Fos-related antigens, which recognizes all of the known members of the Fos family. Neurons located in the amygdala and area postrema were activated transiently after acute infusion of angiotensin II but were not responsive by days 3 or 14. Neurons located in the nucleus of the solitary tract, caudal ventrolateral medulla, and lateral parabrachial nucleus were activated for diameter after balloon deflation, P=0.03). Substernal PPV location, high-pressure post-PPVI dilatation of PPV, pre-PPVI right ventricular outflow tract gradients, and other indicators of PPV compression or asymmetry did not pose increased risk. Patients with type I fracture remain under follow-up. Patients with type II fracture had 2nd PPVI or are awaiting such procedure, and 1 patient with type III fracture required surgical explantation. CONCLUSIONS: Stent fracture after PPVI can be managed effectively by risk stratification, systematic classification, and anticipatory management strategies. Serial x-ray and echocardiography are recommended for surveillance. PMID- 17339543 TI - Adjustable, physiological ventricular restraint improves left ventricular mechanics and reduces dilatation in an ovine model of chronic heart failure. AB - BACKGROUND: Ventricular restraint is a nontransplantation surgical treatment for heart failure. The effect of varying restraint level on left ventricular (LV) mechanics and remodeling is not known. We hypothesized that restraint level may affect therapy efficacy. METHODS AND RESULTS: We studied the immediate effect of varying restraint levels in an ovine heart failure model. We then studied the long-term effect of restraint applied over a 2-month period. Restraint level was quantified by use of fluid-filled epicardial balloons placed around the ventricles and measurement of balloon luminal pressure at end diastole. At 4 different restraint levels (0, 3, 5, and 8 mm Hg), transmural myocardial pressure (P(tm)) and indices of myocardial oxygen consumption (MVO2) were determined in control (n=5) and ovine heart failure (n=5). Ventricular restraint therapy decreased P(tm) and MVO2, and improved mechanical efficiency. An optimal physiological restraint level of 3 mm Hg was identified to maximize improvement without an adverse affect on systemic hemodynamics. At this optimal level, end diastolic P(tm) and MVO2 indices decreased by 27% and 20%, respectively. The serial longitudinal effects of optimized ventricular restraint were then evaluated in ovine heart failure with (n=3) and without (n=3) restraint over 2 months. Optimized ventricular restraint prevented and reversed pathological LV dilatation (130+/-22 mL to 91+/-18 mL) and improved LV ejection fraction (27+/-3% to 43+/-5%). Measured restraint level decreased over time as the LV became smaller, and reverse remodeling slowed. CONCLUSIONS: Ventricular restraint level affects the degree of decrease in P(tm), the degree of decrease in MVO2, and the rate of LV reverse remodeling. Periodic physiological adjustments of restraint level may be required for optimal restraint therapy efficacy. PMID- 17339544 TI - Direct myocardial effects of levosimendan in humans with left ventricular dysfunction: alteration of force-frequency and relaxation-frequency relationships. AB - BACKGROUND: Enthusiasm for the development of Ca2+ sensitizers as inotropic agents for heart failure has been tempered by reports of impaired relaxation. Levosimendan, which increases myofilament Ca2+ sensitivity via Ca2+-dependent binding to troponin C, exerts positive inotropic and lusitropic effects in failing human myocardium in vitro. We sought to determine the direct effects of levosimendan on failing human myocardium in vivo, and in particular whether levosimendan exerts heart rate-dependent effects on systolic or diastolic function. METHODS AND RESULTS: Ten patients with left ventricular dysfunction caused by nonischemic dilated cardiomyopathy (mean left ventricular ejection fraction, 27+/-2%) were instrumented with an infusion catheter in the left main coronary artery, a high-fidelity micromanometer-tipped catheter in the left ventricle, and a bipolar pacing wire in the right atrium. Inotropic (peak +dP/dt) and lusitropic (Tau) responses were assessed during continuous intracoronary drug infusion in sinus rhythm followed by atrial pacing at 20, 40, and 60 beats per minute above the sinus rate. Under control conditions (intracoronary 5% dextrose in water), atrial-pacing tachycardia decreased Tau by 13% (P<0.05), but did not increase +dP/dt. Intracoronary levosimendan (3.75 and 12.5 microg/min for 15 minutes each) increased +dP/dt dose-dependently and decreased Tau over a range of heart rates, but did not alter the slope of the force-frequency or relaxation frequency relationship. CONCLUSIONS: Myocardial calcium sensitization with levosimendan exerts mild inotropic and lusitropic effects in humans with left ventricular dysfunction, but does not alter the force-frequency or relaxation frequency relationship. PMID- 17339545 TI - Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. AB - BACKGROUND: Several clinical studies have demonstrated that levels of adiponectin are significantly reduced in patients with type 2 diabetes and that adiponectin levels are inversely related to the risk of myocardial ischemia. The present study was designed to determine the mechanism by which adiponectin exerts its protective effects against myocardial ischemia/reperfusion. METHODS AND RESULTS: Adiponectin-/- or wild-type mice were subjected to 30 minutes of myocardial ischemia followed by 3 hours or 24 hours (infarct size and cardiac function) of reperfusion. Myocardial infarct size and apoptosis, production of peroxynitrite, nitric oxide (NO) and superoxide, and inducible NO synthase (iNOS) and gp91(phox) protein expression were compared. Myocardial apoptosis and infarct size were markedly enhanced in adiponectin-/- mice (P<0.01). Formation of NO, superoxide, and their cytotoxic reaction product, peroxynitrite, were all significantly higher in cardiac tissue obtained from adiponectin-/- than from wild-type mice (P<0.01). Moreover, myocardial ischemia/reperfusion-induced iNOS and gp91(phox) protein expression was further enhanced, but endothelial NOS phosphorylation was reduced in cardiac tissue from adiponectin-/- mice. Administration of the globular domain of adiponectin 10 minutes before reperfusion reduced myocardial ischemia/reperfusion-induced iNOS/gp91(phox) protein expression, decreased NO/superoxide production, blocked peroxynitrite formation, and reversed proapoptotic and infarct-enlargement effects observed in adiponectin-/- mice. CONCLUSIONS: The present study demonstrates that adiponectin is a natural molecule that protects hearts from ischemia/reperfusion injury by inhibition of iNOS and nicotinamide adenine dinucleotide phosphate-oxidase protein expression and resultant oxidative/nitrative stress. PMID- 17339546 TI - Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo. AB - BACKGROUND: Fluorescence imaging of the heart is currently limited to invasive ex vivo or in vitro applications. We hypothesized that the adaptation of advanced transillumination and tomographic techniques would allow noninvasive fluorescence images of the heart to be acquired in vivo and be coregistered with in vivo cardiac magnetic resonance images. METHODS AND RESULTS: The uptake of the magnetofluorescent nanoparticle CLIO-Cy5.5 by macrophages in infarcted myocardium was studied. Ligation of the left coronary artery was performed in 12 mice and sham surgery in 7. The mice were injected, 48 hours after surgery, with 3 to 20 mg of iron per kilogram of CLIO-Cy5.5. Magnetic resonance imaging and fluorescence molecular tomography were performed 48 hours later. An increase in magnetic resonance imaging contrast-to-noise ratio, indicative of myocardial probe accumulation, was seen in the anterolateral walls of the infarcted mice but not in the sham-operated mice (23.0+/-2.7 versus 5.43+/-2.4; P<0.01). Fluorescence intensity over the heart was also significantly greater in the fluorescence molecular tomography images of the infarcted mice (19.1+/-5.2 versus 5.3+/-1.4; P<0.05). The uptake of CLIO-Cy5.5 by macrophages infiltrating the infarcted myocardium was confirmed by fluorescence microscopy and immunohistochemistry. CONCLUSIONS: Noninvasive imaging of myocardial macrophage infiltration has been shown to be possible by both fluorescence tomography and magnetic resonance imaging. This could be of significant value in both the research and clinical settings. The techniques developed could also be used to image other existing fluorescent and magnetofluorescent probes and could significantly expand the role of fluorescence imaging in the heart. PMID- 17339547 TI - Pulmonary arterial hypertension is linked to insulin resistance and reversed by peroxisome proliferator-activated receptor-gamma activation. AB - BACKGROUND: Patients with pulmonary arterial hypertension (PAH) have reduced expression of apolipoprotein E (apoE) and peroxisome proliferator-activated receptor-gamma in lung tissues, and deficiency of both has been linked to insulin resistance. ApoE deficiency leads to enhanced platelet-derived growth factor signaling, which is important in the pathobiology of PAH. We therefore hypothesized that insulin-resistant apoE-deficient (apoE-/-) mice would develop PAH that could be reversed by a peroxisome proliferator-activated receptor-gamma agonist (eg, rosiglitazone). METHODS AND RESULTS: We report that apoE-/- mice on a high-fat diet develop PAH as judged by elevated right ventricular systolic pressure. Compared with females, male apoE-/- were insulin resistant, had lower plasma adiponectin, and had higher right ventricular systolic pressure associated with right ventricular hypertrophy and increased peripheral pulmonary artery muscularization. Because male apoE-/- mice were insulin resistant and had more severe PAH than female apoE-/- mice, we treated them with rosiglitazone for 4 and 10 weeks. This treatment resulted in markedly higher plasma adiponectin, improved insulin sensitivity, and complete regression of PAH, right ventricular hypertrophy, and abnormal pulmonary artery muscularization in male apoE-/- mice. We further show that recombinant apoE and adiponectin suppress platelet-derived growth factor-BB-mediated proliferation of pulmonary artery smooth muscle cells harvested from apoE-/- or C57Bl/6 control mice. CONCLUSIONS: We have shown that insulin resistance, low plasma adiponectin levels, and deficiency of apoE may be risk factors for PAH and that peroxisome proliferator-activated receptor-gamma activation can reverse PAH in an animal model. PMID- 17339548 TI - Declining into failure: the age-dependent loss of the L-type calcium channel within the sinoatrial node. AB - BACKGROUND: The spontaneous activity of pacemaker cells in the sinoatrial (SA) node controls heart rate under normal physiological conditions. Clinical studies have shown the incidence of SA node dysfunction increases with age and occurs with peak prevalence in the elderly population. The present study investigated whether aging affected the expression of Ca(v)1.2 channels and whether these changes could affect pacemaker activity, in turn leading to age-related SA node degeneration. METHODS AND RESULTS: The SA node region was isolated from the right atrium of guinea pigs between birth and 38 months of age. Immunofluorescence studies showed Ca(v)1.2 protein was present as punctate labeling around the outer membrane of atrial cells but was absent from the center of the SA node. The area lacking Ca(v)1.2-labeled protein progressively increased from 2.06+/-0.1 (mean+/ SEM) mm2 at 1 month to 18.72+/-2.2 mm2 at 38 months (P<0.001). Western blot provided verification that Ca(v)1.2 protein expression within the SA node declined during aging. Functional measurements showed an increased sensitivity to the L-type calcium blocker nifedipine; SA node preparations stopped beating in 100 micromol/L nifedipine at 1 day old, compared with 30 micromol/L at 1 month and 10 micromol/L at 38 months of age. Furthermore, the amplitude of extracellular potentials declined within the center and periphery of the SA node during aging. CONCLUSIONS: The present data show Ca(v)1.2 channel protein decreases concurrently with reduced spontaneous activity of the SA node with increased age, which provides further evidence of mechanisms underlying the age related deterioration of the cardiac pacemaker. PMID- 17339549 TI - Global diastolic strain rate for the assessment of left ventricular relaxation and filling pressures. AB - BACKGROUND: Diastolic strain rate (SR) measurements that comprise all left ventricular (LV) segments are advantageous over myocardial velocity for assessment of diastolic function. Mitral early diastolic velocity (E)/SR ratio during the isovolumetric relaxation (IVR) period can be used to estimate LV filling pressures. METHODS AND RESULTS: Simultaneous echocardiographic imaging and LV pressure measurements (7F catheters) were performed in 7 adult dogs. Loading conditions were altered by saline infusion and caval occlusion, and lusitropic state was changed by dobutamine and esmolol infusion. A curve depicting global SR was derived from each of the 3 apical views, and SR was measured during IVR (SR(IVR)) and early LV filling (SR(E)). SR(IVR) had a strong correlation with time constant of LV pressure decay during the IVR period (tau) (r=-0.83, P<0.001), whereas SR(E) was significantly related to LV end-diastolic pressure (r=0.52, P=0.005) in the experimental stages where tau was <40 ms. In 50 patients with simultaneous right heart catheterization and echocardiographic imaging, mitral E/SR(IVR) ratio had the best correlation with mean wedge pressure (r=0.79, P<0.001), as well as in 24 prospective patients (r=0.84, P=0.001). E/SR(IVR) was most useful in patients with ratio of E to mitral annulus early diastolic velocity (E/Ea ratio) 8 to 15 and was more accurate than E/Ea in patients with normal ejection fraction and regional dysfunction (both P<0.01). CONCLUSIONS: Global SR(IVR) by 2-dimensional speckle tracking is strongly dependent on LV relaxation. E/SR(IVR) can predict LV filling pressures with reasonable accuracy, particularly in patients with normal ejection fraction and in those with regional dysfunction. PMID- 17339550 TI - Glucose levels predict hospitalization for congestive heart failure in patients at high cardiovascular risk. AB - BACKGROUND: Patients with diabetes mellitus (DM) are at high risk of developing congestive heart failure (CHF). However, the relationships between glucose levels and CHF in people with or without a history of DM have not been well characterized. METHODS AND RESULTS: We evaluated the associations between fasting plasma glucose and risk of hospitalization for CHF during follow-up in patients at high cardiovascular risk and without CHF enrolled in a large-scale clinical trials program. Baseline fasting plasma glucose levels were assessed in 31,546 high-risk subjects with > or = 1 coronary, peripheral, or cerebrovascular disease or DM with end-organ damage who are participating in 2 ongoing parallel trials evaluating the effects of telmisartan, ramipril, or their combination (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial [ONTARGET]; n=25,620) and the effects of telmisartan against placebo in angiotensin-converting enzyme-intolerant patients (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease [TRANSCEND]; n=5926). Interim analyses blinded for randomized treatment were performed to compare baseline fasting plasma glucose with the adjusted CHF event rate at a mean follow-up of 886 days. Multivariable Cox regression models were performed, and associations were reported as hazard ratios and 95% confidence intervals. Among all subjects (mean age, 67 years; 69% men), of whom 11,708 (37%) had known DM and 1006 (3.2%) had newly diagnosed DM at baseline, 668 patients were hospitalized for CHF during follow-up. After adjustment for age and sex, a 1 mmol/L-higher fasting plasma glucose was associated with a 1.10-fold-increased risk of CHF hospitalization (95% confidence interval, 1.08 to 1.12; P<0.0001). The association persisted after adjustment for age, sex, smoking, previous myocardial infarction, hypertension, waist-to-hip ratio, creatinine, DM, and use of aspirin, beta-blockers, or statins (hazard ratio, 1.05; 95% confidence interval, 1.02 to 1.08; P<0.001). CONCLUSIONS: Fasting plasma glucose is an independent predictor of hospitalization for CHF in high-risk subjects. These data provide theoretical support for potential direct beneficial effects of glucose lowering in reducing the risk of CHF and suggests the need for specific studies targeted at this issue. PMID- 17339551 TI - Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals. AB - BACKGROUND: Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors. METHODS AND RESULTS: We examined the association of plasma levels of B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide with metabolic risk factors, the metabolic syndrome, and insulin resistance in 3333 Framingham study participants free of heart failure (mean age, 58 years; 54% women). Regression analyses were performed, with adjustment for clinical and echocardiographic variables. Plasma natriuretic peptide levels were inversely associated with all components of the metabolic syndrome except for elevated blood pressure. Adjusted natriuretic peptide levels were lower in persons with the metabolic syndrome compared with those without the metabolic syndrome: In men, B-type natriuretic peptide was 24% lower (P<0.001) and N-terminal pro-atrial natriuretic peptide was 16% lower (P<0.001); in women, B-type natriuretic peptide was 29% lower (P<0.001) and N-terminal pro-atrial natriuretic peptide was 18% lower (P<0.001). Individuals with insulin resistance, as indicated by an elevated homeostasis model assessment (HOMA-IR) index, had lower levels of B-type natriuretic peptide (P=0.009 in men, P<0.001 in women) and N-terminal pro-atrial natriuretic peptide (P<0.001 in men, P=0.001 in women). CONCLUSIONS: Having several metabolic risk factors is associated with low circulating natriuretic peptide levels, even after adjustment for body mass index. These findings raise the possibility that reduced natriuretic peptide activity is a manifestation of the metabolic syndrome, which may have important clinical and pathophysiological implications. PMID- 17339552 TI - Muscarinic modulation of the sodium-calcium exchanger in heart failure. AB - BACKGROUND: The Na-Ca exchanger (NCX) is a critical calcium efflux pathway in excitable cells, but little is known regarding its autonomic regulation. METHODS AND RESULTS: We investigated beta-adrenergic receptor and muscarinic receptor regulation of the cardiac NCX in control and heart failure (HF) conditions in atrially paced pigs. NCX current in myocytes from control swine hearts was significantly increased by isoproterenol, and this response was reversed by concurrent muscarinic receptor stimulation with the addition of carbachol, demonstrating "accentuated antagonism." Okadaic acid eliminated the inhibitory effect of carbachol on isoproterenol-stimulated NCX current, indicating that muscarinic receptor regulation operates via protein phosphatase-induced dephosphorylation. However, in myocytes from atrially paced tachycardia-induced HF pigs, the NCX current was significantly larger at baseline but less responsive to isoproterenol compared with controls, whereas carbachol failed to inhibit isoproterenol-stimulated NCX current, and 8-Br-cGMP did not restore muscarinic responsiveness. Protein phosphatase type 1 dialysis significantly reduced NCX current in failing but not control cells, consistent with NCX hyperphosphorylation in HF. Protein phosphatase type 1 levels associated with NCX were significantly depressed in HF pigs compared with control, and total phosphatase activity associated with NCX was significantly decreased. CONCLUSIONS: We conclude that the NCX is autonomically modulated, but HF reduces the level and activity of associated phosphatases; defective dephosphorylation then "locks" the exchanger in a highly active state. PMID- 17339553 TI - Increased perioperative N-terminal pro-B-type natriuretic peptide levels predict atrial fibrillation after thoracic surgery for lung cancer. AB - BACKGROUND: Postoperative atrial fibrillation (AF) is a complication of thoracic surgery for lung cancer, with a reported incidence that can run as high as 42%. Recently, it has been observed retrospectively that B-type natriuretic peptide predicts AF after cardiac surgery. We performed a prospective study to evaluate the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a marker for risk stratification of postoperative AF in patients undergoing thoracic surgery for lung cancer. METHODS AND RESULTS: We measured NT-proBNP levels in 400 patients (mean age, 62+/-10 years; 271 men) 24 hours before and 1 hour after surgery. The primary end point of the study was the incidence of postoperative AF. Overall, postoperative AF occurred in 72 patients (18%). Eighty-eight patients (22%) showed an elevated perioperative NT-proBNP value. When patients with either preoperatively or postoperatively elevated NT-proBNP were pooled, a greater incidence of AF was observed compared with patients with normal values (64% versus 5%; P<0.001). At multivariable analysis, adjusted for age, gender, major comorbidities, echocardiography parameters, pneumonectomy, and medications, both preoperative and postoperative NT-proBNP values were independent predictors of AF (relative risk, 27.9; 95% CI, 13.2 to 58.9; P<0.001 for preoperative NT proBNP elevation; relative risk, 20.1; 95% CI, 5.8 to 69.4; P<0.001 for postoperative NT-proBNP elevation). CONCLUSIONS: Elevation of perioperative NT proBNP is a strong independent predictor of postoperative AF in patients undergoing thoracic surgery for lung cancer. This finding should facilitate studies of therapies to reduce AF in selected high-risk patients. PMID- 17339554 TI - Impact of prosthesis-patient mismatch on survival after mitral valve replacement. AB - BACKGROUND: We recently reported that valve prosthesis-patient mismatch (PPM) is associated with persisting pulmonary hypertension after mitral valve replacement. Thus, the objective of this study was to evaluate the impact of PPM on mortality in patients undergoing mitral valve replacement. METHODS AND RESULTS: The indexed valve effective orifice area was estimated for each type and size of prosthesis being implanted in 929 consecutive patients and used to define PPM as not clinically significant if > 1.2 cm2/m2, as moderate if > 0.9 and < or = 1.2 cm2/m2, and as severe if < or = 0.9 cm2/m2. Moderate PPM was present in 69% of patients; severe PPM was seen in 9%. For patients with severe PPM, 6-year survival (74+/-5%) and 12-year survival (63+/-7%) were significantly less than for patients with moderate PPM (84+/-1% and 76+/-2%; P=0.027) or nonsignificant PPM (90+/-2% and 82+/-4%; P=0.002). On multivariate analysis, severe PPM was associated with higher mortality (hazard ratio, 3.2; 95% confidence interval, 1.5 to 6.8; P=0.003). CONCLUSIONS: Severe PPM is an independent predictor of mortality after mitral valve replacement. As opposed to other independent risk factors, PPM may be avoided or its severity may be reduced with the use of a prospective strategy at the time of operation. For patients identified as being at risk for severe PPM, every effort should be made to implant a prosthesis with a larger effective orifice area. PMID- 17339556 TI - Images in cardiovascular medicine. High-altitude-induced right-heart failure. PMID- 17339555 TI - Prevention of pulmonary embolism in general surgery patients. PMID- 17339557 TI - Images in cardiovascular medicine. Hypertensive brainstem encephalopathy. PMID- 17339558 TI - Images in cardiovascular medicine. Virtual cardiotomy for preoperative planning. PMID- 17339559 TI - Letter by Andreotti et al regarding article, "Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) study". PMID- 17339560 TI - Pioneers of Cardiology: Donald Ross, DSc, FRCS. Interview by Mark Nicholls. PMID- 17339562 TI - Risk factors for myocardial infarction in Latin America: sobrepeso y obesidad. PMID- 17339563 TI - Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS-II): prologue to COURAGE. PMID- 17339564 TI - Risk factors for acute myocardial infarction in Latin America: the INTERHEART Latin American study. AB - BACKGROUND: Current knowledge of the impact of cardiovascular risk factors in Latin America is limited. METHODS AND RESULTS: As part of the INTERHEART study, 1237 cases of first acute myocardial infarction and 1888 age-, sex-, and center matched controls were enrolled from Argentina, Brazil, Colombia, Chile, Guatemala, and Mexico. History of smoking, hypertension, diabetes mellitus, diet, physical activity, alcohol consumption, psychosocial factors, anthropometry, and blood pressure were recorded. Nonfasting blood samples were analyzed for apolipoproteins A-1 and B-100. Logistic regression was used to estimate multivariate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Persistent psychosocial stress (OR, 2.81; 95% CI, 2.07 to 3.82), history of hypertension (OR, 2.81; 95% CI, 2.39 to 3.31), diabetes mellitus (OR, 2.59; 95% CI, 2.09 to 3.22), current smoking (OR, 2.31; 95% CI, 1.97 to 2.71), increased waist-to-hip ratio (OR for first versus third tertile, 2.49; 95% CI, 1.97 to 3.14), and increased ratio of apolipoprotein B to A-1 (OR for first versus third tertile, 2.31; 95% CI, 1.83 to 2.94) were associated with higher risk of acute myocardial infarction. Daily consumption of fruits or vegetables (OR, 0.63; 95% CI, 0.51 to 0.78) and regular exercise (OR, 0.67; 95% CI, 0.55 to 0.82) reduced the risk of acute myocardial infarction. Abdominal obesity, abnormal lipids, and smoking were associated with high population-attributable risks of 48.5%, 40.8%, and 38.4%, respectively. Collectively, these risk factors accounted for 88% of the population-attributable risk. CONCLUSIONS: Interventions aimed at decreasing behavioral risk factors, lowering blood pressure, and modifying lipids could have a large impact on the risk of acute myocardial infarction among Latin Americans. PMID- 17339565 TI - Nonfatal acute myocardial infarction in Costa Rica: modifiable risk factors, population-attributable risks, and adherence to dietary guidelines. AB - BACKGROUND: Cardiovascular disease, including myocardial infarction (MI), is increasing in developing countries. Knowledge of risk factors and their impact on the population could offer insights into primary prevention. METHODS AND RESULTS: We estimated the population-attributable risk (PAR) for major MI risk factors among Costa Ricans without a history of diabetes, hypertension, or regular use of medication (889 MI cases, 1167 population-based controls). Lifestyle and dietary variables were measured with validated questionnaires. In multivariate analyses, abdominal obesity (PAR, 29.3%), smoking (PAR, 25.6%), nonuse of alcohol (PAR, 14.8%), caffeine intake (PAR, 12.8%), physical inactivity (PAR, 9.6%), and poor diet (PAR, 6.0%) were the most important MI risk factors. Subjects in the favorable categories of the above 6 risk factors showed a lower risk of MI (odds ratio, 0.09; 95% CI, 0.03 to 0.33) than those in the unfavorable categories. Compared with women, men were more likely to smoke (31% versus 10%) but less likely to have waist circumferences greater than Adult Treatment Panel III cutoffs (9% versus 35%). Many subjects did not meet the American Heart Association or World Health Organization/Food and Agriculture Organization dietary guidelines. For instance, 95% obtained > or = 7% of energy from saturated fat, 25% had < or = 5% of energy from polyunsaturated fat, 63% had > or = 1% energy from trans fat, and 53% had low fiber intake (< 25 g/d). CONCLUSIONS: These findings confirm the benefit of a healthy diet, physical activity, moderate alcohol, and cessation of smoking as approaches for the primary prevention of MI. Obesity and smoking were the 2 most important risk factors for nonfatal MI in Costa Rica. PMID- 17339566 TI - Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease. AB - BACKGROUND: Despite routine use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), no conclusive evidence exists that either modality is superior to medical therapy (MT) alone for treating multivessel coronary artery disease with stable angina and preserved ventricular function. METHODS AND RESULTS: The primary end points were total mortality, Q wave myocardial infarction, or refractory angina requiring revascularization. The study comprised 611 patients randomly assigned to undergo CABG (n=203), PCI (n=205), or MT (n=203). At the 5-year follow-up, the primary end points occurred in 21.2% of patients who underwent CABG compared with 32.7% treated with PCI and 36% receiving MT alone (P=0.0026). No statistical differences were observed in overall mortality among the 3 groups. In addition, 9.4% of MT and 11.2% of PCI patients underwent repeat revascularization procedures compared with 3.9% of CABG patients (P=0.021). Moreover, 15.3%, 11.2%, and 8.3% of patients experienced nonfatal myocardial infarction in the MT, PCI, and CABG groups, respectively (P<0.001). The pairwise treatment comparisons of the primary end points showed no difference between PCI and MT (relative risk, 0.93; 95% confidence interval, 0.67 to 1.30) and a significant protective effect of CABG compared with MT (relative risk, 0.53; 95% confidence interval, 0.36 to 0.77). CONCLUSIONS: All 3 treatment regimens yielded comparable, relatively low rates of death. MT was associated with an incidence of long-term events and rate of additional revascularization similar to those for PCI. CABG was superior to MT in terms of the primary end points, reaching a significant 44% reduction in primary end points at the 5-year follow-up of patients with stable multivessel coronary artery disease. PMID- 17339567 TI - Sodium-hydrogen exchanger, cardiac overload, and myocardial hypertrophy. PMID- 17339568 TI - Predictors of mortality in chronic Chagas disease: a systematic review of observational studies. AB - BACKGROUND: Chagas disease is a major cause of morbidity and mortality in Latin America. Knowledge of the predictors of prognosis can help clinical decision making by identifying patients' level of risk. METHODS AND RESULTS: We reviewed the published literature on prognostic factors in patients with Chagas disease by performing a PubMed search for articles published in any language between 1985 and February 2006 and hand searches of the reference lists of retrieved articles. Studies were selected if they included patients in the chronic phase of Chagas disease, analyzed a clearly defined outcome (all-cause mortality, sudden cardiac deaths, and/or cardiovascular deaths), and used multivariable regression models of prognosis. From 606 potentially relevant studies, 12 met the inclusion criteria: 8 clinic-based studies including 3928 patients and 4 hospital-based studies including 349 patients. Impaired left ventricular function by echocardiogram or cineventriculogram was found to be the most common and consistent independent predictor of death. New York Heart Association functional class III/IV and cardiomegaly on the chest radiography also were independently associated with higher mortality. More recently, strong evidence was found that nonsustained ventricular tachycardia on 24-hour Holter monitoring indicated an adverse prognosis. The typical ECG abnormalities showed limited additional prognostic value. Other often-mentioned risk factors, advanced age and male sex, showed inconsistent results. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results. CONCLUSIONS: A systematic review of published studies indicates that impaired left ventricular function, New York Heart Association class III/IV, cardiomegaly, and nonsustained ventricular tachycardia indicate a poor prognosis in patients with chronic Chagas disease. PMID- 17339569 TI - Pathogenesis of chronic Chagas heart disease. AB - BACKGROUND: Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. METHODS AND RESULTS: A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. CONCLUSIONS: Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms. PMID- 17339570 TI - Echocardiography in Chagas heart disease. AB - BACKGROUND: Chagas heart disease is a frequent cause of morbidity and mortality in Latin America. Echocardiography provides useful diagnostic and prognostic information and is an important tool in the management of patients with Chagas disease. METHODS AND RESULTS: A search for relevant publications was obtained from MEDLINE, LILACS, and SCIELO sources. Acute Chagas myocarditis is a rare disorder in which pericardial effusion is frequent. Echocardiography may exclude pericardial tamponade in case of heart failure. Chronic Chagas cardiomyopathy evolves for several decades after the infection. Epidemiological history, positive serology, and suggestive clinical and ECG abnormalities establish the diagnosis. About three quarters of chronic Chagas cardiomyopathy subjects remain asymptomatic with normal (indeterminate form) or abnormal ECGs. Early Doppler abnormalities includes prolongation of isovolumic contraction and relaxation times. Systolic function frequently is normal, but dysfunction may be elicited by stress tests. Half or more of symptomatic patients have a left ventricular apical aneurysm and other segmental contractile abnormalities similar to those seen in coronary heart disease. The dilated nonsegmental form is indistinguishable from dilated cardiomyopathy. Results from univariate and multivariate Cox survival analyses indicate that impaired systolic function and increased ventricular dimensions have significant value in predicting cardiac morbidity and mortality. Cardiac ultrasound commonly is used in the follow-up of patients and in the assessment of various therapeutic modalities. CONCLUSIONS: Echocardiographic and Doppler techniques provide useful structural and functional information in the detection of early myocardial damage, risk assessment of prognosis, disease progression, and management of patients with Chagas disease. PMID- 17339571 TI - The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness. AB - More than 140 million people worldwide live >2500 m above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This latter region has its major population density living above 3500 m. The primary objective of the present study is to review the physiology, pathology, pathogenesis, and clinical features of the heart and pulmonary circulation in healthy highlanders and patients with chronic mountain sickness. A systematic review of worldwide literature was undertaken, beginning with the pioneering work done in the Andes several decades ago. Original articles were analyzed in most cases and English abstracts or translations of articles written in Chinese were reviewed. Pulmonary hypertension in healthy highlanders is related to a delayed postnatal remodeling of the distal pulmonary arterial branches. The magnitude of pulmonary hypertension increases with the altitude level and the degree of exercise. There is reversal of pulmonary hypertension after prolonged residence at sea level. Chronic mountain sickness develops when the capacity for altitude adaptation is lost. These patients have moderate to severe pulmonary hypertension with accentuated hypoxemia and exaggerated polycythemia. The clinical picture of chronic mountain sickness differs from subacute mountain sickness and resembles other chronic altitude diseases described in China and Kyrgyzstan. The heart and pulmonary circulation in healthy highlanders have distinct features in comparison with residents at sea level. Chronic mountain sickness is a public health problem in the Andean mountains and other mountainous regions around the world. Therefore, dissemination of preventive and therapeutic measures is essential. PMID- 17339572 TI - Advances in coronary heart disease surgery in Latin America. AB - BACKGROUND: The beginnings of coronary artery bypass graft in Latin America could be set in the year 1971. Since then, improvements in technique and greater experience have resulted in a rapid increase in the rate of interventions performed in the region. METHODS AND RESULTS: Searches through PubMed and Literatura Latinoamericana y del Caribe en Ciencias de la Salud, as well as personal communications from specialists from Latin America, have been the source of information. Articles were selected by their content related to the theme, and the authors' nationality and information is mainly from Latin America. Demographic information of the population of Latin America denotes higher age averages, and this implies an increase in the severity of comorbidities in patients who undergo surgery. Longer life expectancy and improvements in medical therapy have implied that patients survive a first intervention beyond the expected time a bypass persists patent. Wall vessel properties of arterial conduits, plus a better anastomotic technique, seem to be the current solution to worsening in the coronary health of patients who undergo revascularization surgery in Latin America. CONCLUSIONS: Despite scarce economic investment in medical sciences, many academic groups contribute to the exploration of therapeutic pharmacological combinations and inclusively apply genetic strategies. PMID- 17339573 TI - Hemiblocks revisited. AB - The trifascicular nature of the intraventricular conduction system and the concept of trifascicular block and hemiblock were described by Rosenbaum and his coworkers in 1968. Since then, anatomic, pathological, electrophysiological, and clinical studies have confirmed the original description and scarce advances have been developed on the subject. In the present study, we attempt to review and redefine reliable criteria for the electrocardiographic and vectorcardiographic diagnosis of left anterior and posterior hemiblock. One of the most important problems related to hemiblocks is that they may simulate or conceal the electrocardiographic signs of myocardial infarction or myocardial ischemia and may mask or simulate ventricular hypertrophy. Illustrative examples of these associations are shown to help the interpretation of electrocardiograms. The incidence and prevalence of the hemiblocks is presented based on studies performed in hospital patients and general populations. One of the most common causes of hemiblocks is coronary artery disease, and there is a particularly frequent association between anteroseptal myocardial infarction and left anterior hemiblock. The second most important cause is arterial hypertension, followed by cardiomyopathies and Lev and Lenegre diseases. The hemiblocks may also occur in aortic heart disease and congenital cardiopathies. Left anterior hemiblock is more common in men and increases in frequency with advancing age. Evidence is presented regarding the relationship of spontaneous closure of ventricular septal defects, which may explain the finding of this and other conduction defects in young populations. Isolated left anterior hemiblock is a relatively frequent finding in subjects devoid of evidence of structural heart disease. Conversely, isolated left posterior hemiblock is a very rare finding; its prognostic significance is unknown and is commonly associated with right bundle-branch block. The most remarkable feature of this association is that the prognosis is much more serious with a great propensity to develop complete atrioventricular block and Adams-Stoke seizures. PMID- 17339574 TI - Design of randomized controlled trials. PMID- 17339575 TI - Probing the mRNA processing body using protein macroarrays and "autoantigenomics". AB - Messenger RNA processing bodies (P-bodies) are cellular structures that have a direct role in mRNA degradation. P-bodies have also been implicated in RNAi mediated post-transcriptional gene silencing. Despite the important roles of P bodies in cellular biology, the constituents of P-bodies and their organization have been only partially defined. Approximately 5% of patients with the autoimmune disease primary biliary cirrhosis have antibodies directed against these structures. Recent advances in protein macroarray technology permit the simultaneous screening of thousands of proteins for reactivity with autoantibodies. We used serum from patients with anti-P-body autoantibodies to screen a protein macroarray and identified 67 potential autoantigens. Immunoreactive proteins included four known P-body components and three additional primary biliary cirrhosis autoantigens. Y-box protein 1 (YB-1), a 50 kDa RNA-binding protein that was not previously known to be a P-body component, was recognized by serum from four of seven patients. YB-1 colocalized with P-body components DCP1a and Ge-1. In cells subjected to arsenite-induced oxidative stress, YB-1 localized to TIA-containing stress granules. Both YB-1 and the previously identified P-body component RAP55 translocated from P-bodies to stress granules during oxidative stress. During recovery, however, the reappearance of YB-1 in P-bodies was delayed compared with that of RAP55, suggesting that YB-1 and RAP55 may have different functions. This study demonstrates that the combination of human autoantibodies and protein macroarray technology provides a novel method for identifying and characterizing components of mRNA P-bodies. PMID- 17339576 TI - Coplanar and coaxial orientations of RNA bases and helices. AB - Electrostatic interactions, base-pairing, and especially base-stacking dominate RNA three-dimensional structures. In an A-form RNA helix, base-stacking results in nearly perfect parallel orientations of all bases in the helix. Interestingly, when an RNA structure containing multiple helices is visualized at the atomic level, it is often possible to find an orientation such that only the edges of most bases are visible. This suggests that a general aspect of higher level RNA structure is a coplanar arrangement of base-normal vectors. We have analyzed all solved RNA crystal structures to determine the degree to which RNA base-normal vectors are globally coplanar. Using a statistical test based on the Watson Girdle distribution, we determined that 330 out of 331 known RNA structures show statistically significant (p < 0.05; false discovery rate [FDR] = 0.05) coplanar normal vector orientations. Not surprisingly, 94% of the helices in RNA show bipolar arrangements of their base-normal vectors (p < 0.05). This allows us to compute a mean axis for each helix and compare their orientations within an RNA structure. This analysis revealed that 62% (208/331) of the RNA structures exhibit statistically significant coaxial packing of helices (p < 0.05, FDR = 0.08). Further analysis reveals that the bases in hairpin loops and junctions are also generally planar. This work demonstrates coplanar base orientation and coaxial helix packing as an emergent behavior of RNA structure and may be useful as a structural modeling constraint. PMID- 17339577 TI - Low LDL cholesterol, statins, and brain hemorrhage: should we worry? PMID- 17339578 TI - Hybridize and personalize: the new age of syndromal mental retardation diagnostics. PMID- 17339579 TI - Assessment: use of epidural steroid injections to treat radicular lumbosacral pain: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. AB - Based on the available evidence, the Therapeutics and Technology Assessment subcommittee concluded that 1) epidural steroid injections may result in some improvement in radicular lumbosacral pain when assessed between 2 and 6 weeks following the injection, compared to control treatments (Level C, Class I-III evidence). The average magnitude of effect is small and generalizability of the observation is limited by the small number of studies, highly selected patient populations, few techniques and doses, and variable comparison treatments; 2) in general, epidural steroid injection for radicular lumbosacral pain does not impact average impairment of function, need for surgery, or provide long-term pain relief beyond 3 months. Their routine use for these indications is not recommended (Level B, Class I-III evidence); 3) there is insufficient evidence to make any recommendation for the use of epidural steroid injections to treat radicular cervical pain (Level U). PMID- 17339580 TI - Identification of the penumbra and infarct core on hyperacute noncontrast and perfusion CT. AB - OBJECTIVES: To correlate the two types of early ischemic change on noncontrast CT (NCCT) (parenchymal hypoattenuation [PH] and isolated focal swelling [IFS]) with concurrent assessment of cerebral perfusion and to compare their rates of progression to infarction. METHODS: We assessed cortical regions on NCCT for early ischemic change. Quantitative perfusion values were calculated for cortical regions from acute CT perfusion (CTP) maps of cerebral blood volume (CBV), blood flow (CBF), and mean transit time (MTT). Reperfusion and presence of infarction were determined from follow-up MRI. RESULTS: We studied 40 patients with sub-6 hour anterior circulation ischemic stroke; 19 received IV recombinant tissue plasminogen activator. Of the 202 regions acutely hypoperfused on CTP, 123 were normal on NCCT, 58 had PH, and 21 had IFS. Acute CBV was low in PH regions, and elevated in IFS regions. Acute CBF was reduced in IFS regions, but more so in PH regions. Progression to infarction occurred in virtually all PH regions, but IFS regions had much lower rates of infarction with major reperfusion. Acute CBV in hypoperfused normal NCCT regions ranged from reduced to elevated, with substantially differing risk of infarction. CONCLUSIONS: Isolated focal swelling identifies penumbral tissue and parenchymal hypoattenuation identifies infarct core. Although this has prognostic implications when assessing patient suitability for thrombolytic therapy, the majority of acutely hypoperfused regions appear normal on noncontrast CT. Perfusion CT can stratify the level of risk of subsequent infarction for normal-appearing regions on noncontrast CT. PMID- 17339581 TI - DNA microarray analysis identifies candidate regions and genes in unexplained mental retardation. AB - OBJECTIVE: Because in most patients with mental retardation (MR), who constitute 2 to 3% of the population, the etiology remains unknown, we wanted to identify novel chromosomal candidate regions and genes associated with the MR phenotype. METHODS: We screened for microimbalances in 60 clinically well-characterized patients with unexplained MR mostly combined with congenital anomalies. Genome wide array-based comparative genomic hybridization was performed on DNA microarrays with an average resolution of <0.5 Mb. We verified every nonpolymorphic array clone outside the diagnostic thresholds by fluorescence in situ hybridization and performed breakpoint analyses on confirmed imbalances. RESULTS: Six presumably causal microimbalances were detected, five of which have not been reported. Microdeletions were found in five patients with MR and distinctive facial features, who also had neurologic findings (three cases), brain anomalies (two cases), and growth retardation (two cases), in chromosomal bands 6q11.1-q13 (10.8 Mb), Xq21.31-q21.33 (4.0 Mb), 1q24.1-q24.2 (3.8 Mb), 19p13.12 (2.1 Mb), and 4p12-p13 (1.1 Mb). One microduplication was detected in 22q11.2 (2.8 Mb) including the DiGeorge syndrome critical region in a patient with mild MR, microcephaly at birth, and dysmorphisms. Three imbalances were shown to be de novo and two inherited. The Xq21 microdeletion in a boy with borderline intellectual functioning was inherited from a normal mother; the 22q11.2 microduplication was inherited from a normal father and was present in two affected siblings. CONCLUSION: We could identify novel microimbalances as the probable cause of mental retardation in 10% of patients with unclear etiology. The gene content of the microimbalances was found to correlate with phenotype severity. Precise breakpoint analyses allowed the identification of deleted genes presumably causing mental retardation. PMID- 17339582 TI - Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study. AB - BACKGROUND: Longitudinal studies have shown that high serum total cholesterol (TC) at midlife is a risk factor for dementia/Alzheimer disease. The significance of TC later in life is unclear. OBJECTIVE: To investigate changes in serum TC from midlife to late life and their relationship with late-life cognition. METHODS: Participants of the Cardiovascular Risk Factors, Aging and Dementia study were derived from random, population-based samples previously studied in a survey in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1,449 individuals aged 65 to 79 were reexamined in 1998. RESULTS: Serum TC levels decreased in most individuals. High midlife TC represented a risk factor for more severe cognitive impairment later in life, and the values were significantly different between the control, mild cognitive impairment, and dementia groups. There were no significant differences in serum TC at reexamination. A moderate decrease in serum TC from midlife to late life (0.5 to 2 mmol/L) was significantly associated with the risk of a more impaired late-life cognitive status, even after adjusting for age, follow-up time, sex, years of formal education, midlife cholesterol, changes in body mass index, APOE epsilon4 genotype, history of myocardial infarction/stroke/diabetes, and lipid-lowering treatment. CONCLUSIONS: The relationship between serum total cholesterol (TC) and dementia seems to be bidirectional. High midlife serum TC is a risk factor for subsequent dementia/Alzheimer disease, but decreasing serum TC after midlife may reflect ongoing disease processes and may represent a risk marker for late-life cognitive impairment. PMID- 17339583 TI - Cortical biochemistry in MCI and Alzheimer disease: lack of correlation with clinical diagnosis. AB - OBJECTIVE: Mild cognitive impairment, hypothesized to be prodromal Alzheimer disease (AD), shows abundant senile plaques and neurofibrillary tangles, but its biochemical correlates remain undefined. METHODS: Biochemical profiles of Abeta, tau, alpha-synuclein, and oxidative pathologies were characterized in middle frontal gyrus, inferior parietal cortex, and entorhinal cortex in postmortem frozen brains from subjects diagnosed antemortem with no cognitive impairment, mild cognitive impairment, or AD. RESULTS: Insoluble Abeta and tau, as well as tissue isoprostanes, from each brain region analyzed did not correlate with the clinical diagnosis proximate to death, but insoluble Abeta and 8,12-iso iPF(2alpha)-VI levels from gray matter of all brain regions correlated strongly with the burden of AD pathology, whereas insoluble tau did not. CONCLUSIONS: The biochemical alterations in cortical tau, Abeta, and isoprostane do not reflect the onset of clinical dementia. PMID- 17339584 TI - Temporal relationship between cigarette smoking and risk of Parkinson disease. AB - OBJECTIVE: To characterize further the relationship between smoking history and Parkinson disease (PD) risk by considering temporal and qualitative features of smoking exposure, including duration, average intensity, and recentness, as well as the relative importance of smoking during different periods of life. METHODS: We prospectively assessed incident PD from 1992 to 2001 among 79,977 women and 63,348 men participating in the Cancer Prevention Study II Nutrition Cohort, according to their cigarette smoking status and lifetime smoking histories. RESULTS: During follow-up, 413 participants had definite or probable PD confirmed by their treating neurologists or medical record review. Compared with never smokers, former smokers had a relative risk (RR) of 0.78 (95% CI 0.64 to 0.95) and current smokers had an RR of 0.27 (95% CI 0.13 to 0.56). On average, participants with more years smoked, more cigarettes per day, older age at quitting smoking, and fewer years since quitting smoking had lower PD risk. The relative risks and trends did not vary significantly by sex. The cumulative incidence of PD was lowest among participants who quit smoking at later ages. A 30% to 60% decreased risk of PD was apparent for smoking as early as 15 to 24 years before symptom onset, but not for smoking 25 or more years before onset. CONCLUSIONS: The lower risk of Parkinson disease among current and former smokers varied with smoking duration, intensity, and recentness. The dependence of this association on the timing of smoking during life is consistent with a biologic effect. PMID- 17339585 TI - Toothbrushing-induced epilepsy with structural lesions in the primary somatosensory area. AB - We report three patients with reflex toothbrushing-induced epilepsy associated with small circumscribed structural lesions in the primary somatosensory cortex in close proximity to the hand and speech motor areas. Sensory symptoms were observed at clinical onset with localizing focal ictal and interictal epileptiform discharges on EEG. These cases refine the localization, possible mechanisms of epileptogenesis, and classification of this reflex epilepsy. PMID- 17339586 TI - Distal arthrogryposis and muscle weakness associated with a beta-tropomyosin mutation. AB - Tropomyosin (TM), a sarcomeric thin-filament protein, plays an essential part in muscle contraction by regulating actin-myosin interaction. We describe two patients, a woman and her daughter, with muscle weakness and distal arthrogryposis (DA) type 2B, caused by a heterozygous missense mutation, R133W, in TPM2, the gene encoding beta-TM. Our results demonstrate the involvement of muscle dysfunction in the pathogenesis of DA and the fact that DA2B may be caused by mutations in TPM2. PMID- 17339587 TI - Loss of anisotropy in trigeminal neuralgia revealed by diffusion tensor imaging. AB - We studied the trigeminal nerve in seven healthy volunteers and six patients with trigeminal neuralgia using the diffusion tensor imaging derived parameter fractional anisotropy (FA). While controls did not show a difference between both sides, there was a reduction of FA in the affected nerve in three of six patients with accompanying nerve-vessel conflict and atrophy. Reversibility of abnormally low FA values was demonstrated in one patient successfully treated with microvascular decompression. PMID- 17339588 TI - Age at onset determines the occurrence of the progressive phase of multiple sclerosis. AB - We investigated the influence of age at disease onset on timing of the progressive phase in 957 patients with multiple sclerosis (MS). Age at onset powerfully predicts the probability of developing a primary progressive form of the disease. Moreover, age at onset strongly determines the time to conversion to secondary progression for patients presenting with a relapsing form. This suggests that age at onset strongly influences the neurodegenerative component of MS. PMID- 17339589 TI - A 63-year-old man with headaches and behavioral deterioration. PMID- 17339590 TI - High-resolution MRI of isolated intraluminal clot of the common carotid artery. PMID- 17339591 TI - MR tractography depicting damage to the arcuate fasciculus in a patient with conduction aphasia. PMID- 17339592 TI - DRD3 variant and risk of essential tremor. PMID- 17339593 TI - Corticobasal degeneration presenting with progressive spasticity. PMID- 17339594 TI - Pure autonomic failure followed by amyotrophy. PMID- 17339595 TI - In Alzheimer disease, increased wake fragmentation found in those with lower hypocretin-1. PMID- 17339596 TI - Out-of-body experience and arousal. PMID- 17339597 TI - Practice advisory: utility of surgical decompression for treatment of diabetic neuropathy: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. PMID- 17339598 TI - Effect of lamotrigine on cognition in children with epilepsy. PMID- 17339599 TI - Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. PMID- 17339600 TI - Clinical enzymology: enzymes as medicine. PMID- 17339601 TI - Ockham's razor and selective androgen receptor modulators (SARMs): are we overlooking the role of 5alpha-reductase? AB - Selective Androgen Receptor Modulators (SARMs) are a novel class of AR ligands that possess tissue-selective pharmacological activities. SARMs of various chemical structures have been discovered and characterized, and lead compounds with much improved specificity for AR, in vivo pharmacokinetic profiles, and higher degree of tissue selectivity have entered clinical development, and are expected to dramatically expand the clinical applications of androgens. With the rapid progress in SARM discovery and increasing demand for mechanism-based drug design, more and more research efforts have been devoted to the mechanisms of action of the observed tissue selectivity of SARMs. There is increasing enthusiasm in adapting the molecular mechanisms of action from SERM research to the SARM field; however, is the SARM story really so complicated? The tissue specific expression of 5alpha-reductase might provide a simple explanation for this puzzle. PMID- 17339602 TI - The fight against tamoxifen resistance in breast cancer therapy: a new target in the battle? AB - Tamoxifen is one of the most successful and widely used chemopreventive agents ever, and is an effective therapeutic agent for inhibiting growth of hormone receptor positive breast cancers. Tamoxifen and some of its metabolites bind to estrogen receptors and allow subsequent DNA binding at estrogen responsive genes, blocking some estrogenic signals while maintaining others, depending on the tissue. When used therapeutically for up to five years, cases of tamoxifen resistance appear, requiring alternative therapies. One recent proposal uniquely targets a zinc finger of the DNA binding domain of estrogen receptors, rather than the ligand binding domain, to circumvent resistance. In light of the most recent clinical data, however, it is now clear that aromatase inhibitors are the preferred first line therapy for all stages of breast cancer in post-menopausal women, whether they have had previous tamoxifen exposure or resistance. PMID- 17339603 TI - G protein-coupled time travel: evolutionary aspects of GPCR research. AB - The common seven-transmembrane-domain (TMD) architecture of G protein-coupled receptors (GPCRs) has been preserved over a vast period of time, and highly conserved amino acid motifs and residues have evolved to establish ligand and signal transduction specificities. The mining of evolutionary data from sequenced genomes and targeted retrieved orthologs has proven helpful for understanding the physiological relevance of individual GPCRs and for interpreting the clinical significance of GPCR mutations in structural terms. Sequence analysis of GPCR pseudogenes, which are considered as genomic traces of past functions, as well as recent success in sequence analysis of GPCR genes from extinct species, provide further information. This review discusses recent advances and approaches aimed at developing a better understanding of GPCR biology based on evolutionary data. PMID- 17339604 TI - Unraveling the story of NGF-mediated sensitization of nociceptive sensory neurons: ON or OFF the Trks? AB - Nerve Growth Factor (NGF) is produced by and affects a number of immune and inflammatory cells. As part of the inflammatory response, NGF directly or indirectly alters the sensitivity of small diameter sensory neurons that communicate noxious information. The question remains as to the receptors and intracellular signaling cascades that mediate this sensitizing action of NGF. Although the general consensus is that NGF produces peripheral sensitization by activating TrkA, recent work suggests that p75 also contributes. Thus, both NGF receptors appear to contribute to peripheral sensitization although whether they act independently or together remains to be determined. Furthermore, controversy exists as to the downstream signaling pathways involved in NGF-induced peripheral sensitization. PMID- 17339605 TI - IFI16 in human prostate cancer. AB - Increased expression of IFI16 protein (encoded by the IFI16 gene) in normal human prostate epithelial cells is associated with cellular senescence-associated cell growth arrest. Consistent with a role for IFI16 protein in cellular senescence, the expression of IFI16 protein is either very low or not detectable in human prostate cancer cell lines. We now report that treatment of DU-145 and LNCaP prostate cancer cell lines with histone deacetylase inhibitor trichostatin A (TSA) or CGK1026 resulted in transcriptional activation of the IFI16 gene. The induction of IFI16 protein in LNCaP cells was dependent on the duration of TSA treatment. Furthermore, TSA treatment of LNCaP cells up-regulated the expression of Janus-activated kinase 1 protein kinase and modulated the transcription of certain IFN-activatable genes. However, overexpression of exogenous Janus activated kinase 1 protein in LNCaP cells and treatment of cells with IFNs (alpha and gamma) did not increase the expression of IFI16. Instead, the transcriptional activation of IFI16 gene by TSA treatment of LNCaP cells was dependent on transcriptional activation by c-Jun/activator protein-1 transcription factor. Importantly, increased expression of IFI16 in LNCaP cells was associated with decreases in the expression of androgen receptor and apoptosis of cells. Conversely, knockdown of IFI16 expression in TSA-treated LNCaP cells increased androgen receptor protein levels with concomitant decreases in apoptosis. Together, our observations provide support for the idea that histone deacetylase dependent transcriptional silencing of the IFI16 gene in prostate epithelial cells contributes to the development of prostate cancer. PMID- 17339606 TI - Haplotype effects on matrix metalloproteinase-1 gene promoter activity in cancer cells. AB - Increased expression of matrix metalloproteinase-1 (MMP1) is associated with poor prognosis in cancers. Several single nucleotide polymorphisms (-1607GG>G, 839G>A, -755G>T, -519A>G, -422T>A, -340C>T, and 320C>T) in the MMP1 gene promoter have recently been identified. In this study, we assessed the functional effects of these polymorphisms on MMP1 gene promoter activity in cell lines of melanoma (A2058 and A375), breast cancer (MCF7 and MDA-MB-231), lung cancer (A549 and H69), and colorectal cancer (HT-29, SW-620) by comparing the promoter strengths of 10 most common haplotypes deriving from these polymorphisms. In A2058 cells, the GG-G-G-A-T-T-T and GG-G-G-A-C-T haplotypes had 2-fold higher promoter activity than the GG-G-T-A-T-T-C, GG-G-G-A-A-T-T, GG-G-G-A-T-T-C, and GG-G-G-A-A C-T haplotypes, which in turn, had 3-fold higher promoter activity than the G-G-T A-A-C-T, G-A-T-G-T-T-T, G-A-T-G-A-C-T, and G-A-T-G-A-T-G haplotypes. In A375 and MDA-MB-231 cells, high expression haplotypes include not only the -1607GG-bearing haplotypes but also the G-A-T-G-A-T-T haplotype containing the -1607G allele. A similar trend was detected in A549 cells. In addition, in A549 cells, the GG-G-G A-T-T-T haplotype had >2-fold higher promoter activity than several other -1607GG bearing haplotypes. In MCF7 cells, the GG-G-G-A-T-T-T and G-G-T-A-A-C-T haplotypes had 1.5- to 4-fold higher promoter activity than the other haplotypes. These results suggest that the polymorphisms exert haplotype effects on the transcriptional regulation of the MMP1 gene in cancer cells, and indicate a need to examine haplotypes rather than any single polymorphism in genetic epidemiologic studies of the MMP1 gene in cancers. PMID- 17339607 TI - Pantomime of tool use depends on integrity of left inferior frontal cortex. AB - Pantomime of tool use is a frequently used test for apraxia. For basic cognitive neuroscience, pantomime of tool use is of interest because it constitutes a link between instrumental and communicative manual actions. We used lesion subtraction analysis to determine the locations specifically associated with defective pantomime of tool use in patients with left-brain damage and aphasia. Subtraction of lesions of patients with normal pantomime from those with defective pantomime yielded a maximum difference in the inferior frontal gyrus and adjacent portions of the insula and precentral gyrus. This result remained essentially the same when possible confounding influences of impaired language comprehension and of lesion size were controlled by selecting patients equated on these measures and when only patients with preserved imitation of gestures were considered. By contrast, parietal lesions did not have a specific impact on pantomime. We speculate that the vulnerability of pantomime to lesions of left inferior frontal cortex is due to the high demands on selection of a very restrained range of features out of the many features that may come to mind when imagining the actual use of the tool. PMID- 17339608 TI - Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells. AB - Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects, the underlying mechanisms of which remain unclear. In the current study, we questioned whether CBD modulates activation of mast cells, key players in inflammation. By using the rat basophilic leukemia mast cell line (RBL-2H3), we demonstrate that CBD (3-10 muM) augments beta-hexosaminidase release, a marker of cell activation, from antigen-stimulated and unstimulated cells via a mechanism, which is not mediated by G(i)/G(o) protein-coupled receptors but rather is associated with a robust rise in intracellular calcium ([Ca(2+)](i)) levels sensitive to clotrimazole and nitrendipine (10-30 muM). This action, although mimicked by Delta(9)-tetrahydrocannabinol (THC), is opposite to that inhibitory, exerted by the synthetic cannabinoids WIN 55,212-2 and CP 55,940. Moreover, the vanilloid capsaicin, a full agonist of transient receptor potential channel VR1, did not affect [Ca(2+)](i)levels in the RBL-2H3 cells, thus excluding the involvement of this receptor in the CBD-mediated effects. Together, these results support existence of yet-to-be identified sites of interaction, i.e., receptors and/or ion channels associated with Ca(2+) influx of natural cannabinoids such as CBD and THC, the identification of which has the potential to provide for novel strategies and agents of therapeutic interest. PMID- 17339609 TI - Eosinophils develop in distinct stages and are recruited to peripheral sites by alternatively activated macrophages. AB - Eosinophils are associated with allergic diseases and helminth infections. Development of these cells and recruitment to peripheral tissues are only partially understood. Distinct stages of eosinophil development in fetal liver, bone marrow, and blood could be identified using IL-4 reporter mice and mAb against FIRE, Siglec-F, and CCR3. Immature eosinophils were present in the fetal liver and could reconstitute the eosinophil compartment in irradiated recipient mice. In adult mice, eosinophil maturation proceeded from CCR3(-) to CCR3(+) cells in the bone marrow and was accompanied with changes in the transcriptional profile. Eosinophils appeared as activated cells in lung, thymus, lymph nodes, and Peyer's patches but remained in a resting state in bone marrow, blood, and spleen. Mixed bone marrow chimeras revealed that recruitment to lung and peritoneum was dependent on Stat6 expression in noneosinophils. Alternatively activated macrophages contributed substantially to tissue recruitment of eosinophils, providing a novel basis for development of therapeutic approaches to lower tissue eosinophilia. PMID- 17339610 TI - Dissociation between the translocation and the activation of Akt in fMLP stimulated human neutrophils--effect of prostaglandin E2. AB - PGE(2) and other cAMP-elevating agents are known to down-regulate most functions stimulated by fMLP in human polymorphonuclear neutrophils. We reported previously that the inhibitory potential of PGE(2) resides in its capacity to suppress fMLP stimulated PI-3Kgamma activation via the PGE(2) receptor EP(2) and hence, to decrease phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P(3)] formation. Akt activity is stimulated by fMLP through phosphorylation on threonine 308 (Thr308) and serine 473 (Ser473) by 3-phosphoinositide-dependent kinase 1 (PDK1) and MAPK AP kinase (APK)-APK-2 (MAPKAPK-2), respectively, in a PI-3K-dependent manner. Despite the suppression of fMLP-induced PI-3Kgamma activation observed in the presence of PGE(2), we show that Akt is fully phosphorylated on Thr308 and Ser473. However, fMLP-induced Akt translocation is decreased markedly in this context. PGE(2) does not affect the phosphorylation of MAPKAPK-2 but decreases the translocation of PDK1 induced by fMLP. Other cAMP-elevating agents such as adenosine (Ado) similarly block the fMLP-induced PI-3Kgamma activation process but do not inhibit Akt phosphorylation. However, Akt activity stimulated by fMLP is down-regulated slightly by agonists that elevate cAMP levels. Whereas protein kinase A is not involved in the maintenance of Akt phosphorylation, it is required for the inhibition of Akt translocation by PGE(2). Moreover, inhibition of fMLP-stimulated PI-3Kdelta activity by the selective inhibitor IC87114 only partially affects the late phase of Akt phosphorylation in the presence of PGE(2). Taken together, these results suggest that cAMP-elevating agents, such as PGE(2) or Ado, are able to induce an alternative mechanism of Akt activation by fMLP in which the translocation of Akt to PI(3,4,5)P(3)-enriched membranes is not required prior to its phosphorylation. PMID- 17339611 TI - Expression of aquaporin water channels in rat taste buds. AB - In order to gain insight into the molecular mechanisms that allow taste cells to respond to changes in their osmotic environment, we have used primarily immunocytochemical and molecular approaches to look for evidence of the presence of aquaporin-like water channels in taste cells. Labeling of isolated taste buds from the fungiform, foliate, and vallate papillae in rat tongue with antibodies against several of the aquaporins (AQPs) revealed the presence of AQP1, AQP2, and AQP5 in taste cells from these areas. AQP3 antibodies failed to label isolated taste buds from any of the papillae. There was an apparent difference in the regional localization of AQP labeling within the taste bud. Antibodies against AQP1 and AQP2 labeled predominantly the basolateral membrane, whereas the AQP5 label was clearly evident on both the apical and basolateral membranes of cells within the taste bud. Double labeling revealed that AQP1 and AQP2 labeled many, but not all, of the same taste cells. Similar double-labeling experiments with anti-AQP2 and anti-AQP5 clearly showed that AQP5 was expressed on or near the apical membranes whereas AQP2 was absent from this area. The presence of these 3 types of AQPs in taste buds but not in non-taste bud-containing epithelia was confirmed using reverse transcription-polymerase chain reaction. Experiments using patch clamp recording showed that the AQP inhibitor, tetraethylammonium, significantly reduced hypoosmotic-induced currents in rat taste cells. We hypothesize that the AQPs may play roles both in the water movement underlying compensatory mechanisms for changes in extracellular osmolarity and, in the case of AQP5 in particular, in the gustatory response to water. PMID- 17339612 TI - Reproducible research: moving toward research the public can really trust. AB - A community of scientists arrives at the truth by independently verifying new observations. In this time-honored process, journals serve 2 principal functions: evaluative and editorial. In their evaluative function, they winnow out research that is unlikely to stand up to independent verification; this task is accomplished by peer review. In their editorial function, they try to ensure transparent (by which we mean clear, complete, and unambiguous) and objective descriptions of the research. Both the evaluative and editorial functions go largely unnoticed by the public--the former only draws public attention when a journal publishes fraudulent research. However, both play a critical role in the progress of science. This paper is about both functions. We describe the evaluative processes we use and announce a new policy to help the scientific community evaluate, and build upon, the research findings that we publish. PMID- 17339613 TI - Summaries for patients. Anxiety disorders in primary care patients. PMID- 17339614 TI - Summaries for patients. Parathyroid hormone (1-84) and risk for spinal fractures in women with osteoporosis. PMID- 17339615 TI - Summaries for patients. Aspirin or nonsteroidal anti-inflammatory drugs for the prevention of colorectal cancer: U.S. Preventive Services Task Force recommendations. PMID- 17339616 TI - In the clinic. Peripheral arterial disease. PMID- 17339617 TI - Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. AB - BACKGROUND: Anxiety, although as common as depression, has received less attention and is often undetected and undertreated. OBJECTIVE: To determine the current prevalence, impairment, and comorbidity of anxiety disorders in primary care and to evaluate a brief measure for detecting these disorders. DESIGN: Criterion-standard study performed between November 2004 and June 2005. SETTING: 15 U.S. primary care clinics. PARTICIPANTS: 965 randomly sampled patients from consecutive clinic patients who completed a self-report questionnaire and agreed to a follow-up telephone interview. MEASUREMENTS: 7-item anxiety measure (Generalized Anxiety Disorder [GAD]-7 scale) in the clinic, followed by a telephone-administered, structured psychiatric interview by a mental health professional who was blinded to the GAD-7 results. Functional status (Medical Outcomes Study Short Form-20), depressive and somatic symptoms, and self-reported disability days and physician visits were also assessed. RESULTS: Of the 965 patients, 19.5% (95% CI, 17.0% to 22.1%) had at least 1 anxiety disorder, 8.6% (CI, 6.9% to 10.6%) had posttraumatic stress disorder, 7.6% (CI, 5.9% to 9.4%) had a generalized anxiety disorder, 6.8% (CI, 5.3% to 8.6%) had a panic disorder, and 6.2% (CI, 4.7% to 7.9%) had a social anxiety disorder. Each disorder was associated with substantial impairment that increased significantly (P < 0.001) as the number of anxiety disorders increased. Many patients (41%) with an anxiety disorder reported no current treatment. Receiver-operating characteristic curve analysis showed that both the GAD-7 scale and its 2 core items (GAD-2) performed well (area under the curve, 0.80 to 0.91) as screening tools for all 4 anxiety disorders. LIMITATION: The study included a nonrandom sample of selected primary care practices. CONCLUSIONS: Anxiety disorders are prevalent, disabling, and often untreated in primary care. A 2-item screening test may enhance detection. PMID- 17339618 TI - Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. AB - BACKGROUND: Recombinant human parathyroid hormone (1-84) (PTH) increases bone mass and strength and improves bone quality by stimulating new bone formation. OBJECTIVE: To determine the safety of PTH and its effect on the incidence of vertebral fractures in postmenopausal women with osteoporosis. DESIGN: 18-month, randomized, double-blind, placebo-controlled, parallel-group study. SETTING: 168 centers in 9 countries. PATIENTS: 2532 postmenopausal women with low bone mineral density at the hip or lumbar spine. INTERVENTIONS: Women received 100 mug of recombinant human PTH or placebo daily by subcutaneous injection. All received calcium, 700 mg/d, and vitamin D3, 400 U/d. MEASUREMENTS: New or worsened vertebral fractures (primary outcome) and changes in bone mineral density and safety (secondary outcomes). RESULTS: 67.2% of patients who received at least 1 dose of the study drug completed the study. Parathyroid hormone reduced the risk for new or worsened vertebral fractures, but in sensitivity analyses, the magnitude of the reduction was changed with assumptions about fracture incidence in patients who did not complete the study (relative risk assuming no fractures, 0.42 [95% CI, 0.24 to 0.72] [P = 0.001]; relative risk assuming fracture incidence observed in all patients who completed the trial, 0.60 [CI, 0.36 to 1.00] [P = 0.05]; relative risk assuming fracture incidence observed in the placebo group, 0.62 [CI, 0.37 to 1.04] [P = 0.07]). Compared with placebo, mean bone mineral density increased at the spine by 6.9% (CI, 6.4% to 7.4%) and at the hip by 2.1% (CI, 1.7% to 2.5%) but decreased at the forearm in the PTH-treated group. Parathyroid hormone treatment increased the percentage of participants with hypercalciuria, hypercalcemia, and nausea by 24% (CI, 20% to 27%), 23% (CI, 21% to 26%), and 14% (CI, 11% to 16%), respectively, compared with placebo. LIMITATIONS: Baseline serum PTH and vitamin D levels were not measured. Many patients discontinued the trial prematurely. CONCLUSIONS: Parathyroid hormone (1 84) reduced the overall risk for new or worsened vertebral fracture in postmenopausal women with osteoporosis. Hypercalciuria, hypercalcemia, and nausea were more common in women who took the drug. Although the magnitude of the reduction was sensitive to assumptions about fracture incidence in patients who did not complete the study, the findings suggest that PTH provides an alternative therapeutic option for fracture prevention. PMID- 17339619 TI - Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. AB - BACKGROUND: Until recently, the tuberculin skin test was the only test for detecting latent tuberculosis (TB) infection, but 2 ex vivo interferon-gamma release assays (IGRAs) are now commercially licensed. PURPOSE: To estimate sensitivity, specificity, and reproducibility of IGRAs (commercial or research versions of QuantiFERON [QFT] and Elispot) for diagnosing latent TB infection in healthy and immune-suppressed persons. DATA SOURCES: The authors searched MEDLINE and reviewed citations of all original articles and reviews for studies published in English. STUDY SELECTION: Studies had evaluated IGRAs using Mycobacterium tuberculosis-specific antigens (RD1 antigens) and overnight (16- to 24-h) incubation times. Reference standards had to be clearly defined without knowledge of test results. DATA EXTRACTION AND QUALITY ASSESSMENT: Specific criteria for quality assessment were developed for sensitivity, specificity, and reproducibility. DATA SYNTHESIS: When newly diagnosed active TB was used as a surrogate for latent TB infection, sensitivity of all tests was suboptimal, although it was higher with Elispot. No test distinguishes active TB from latent TB. Sensitivity of the tuberculin skin test and IGRAs was similar in persons who were categorized into clinical gradients of exposure. Pooled specificity was 97.7% (95% CI, 96% to 99%) and 92.5% (CI, 86% to 99%) for QFT and for Elispot, respectively. Both assays were more specific than the tuberculin skin test in samples vaccinated with bacille Calmette-Guerin. Elispot was more sensitive than the tuberculin skin test in 3 studies of immune-compromised samples. Discordant tuberculin skin test and IGRA reactions were frequent and largely unexplained, although some may be related to varied definitions of positive test results. Reversion of IGRA results from positive to negative was common in 2 studies in which it was assessed. LIMITATIONS: Most studies used cross-sectional designs with the inherent limitation of no gold standard for latent TB infection, and most involved small samples with a widely varying likelihood of true-positive and false-positive test results. There is insufficient evidence on IGRA performance in children, immune-compromised persons, and the elderly. CONCLUSIONS: New IGRAs show considerable promise and have excellent specificity. Additional studies are needed to better define their performance in high-risk populations and in serial testing. Longitudinal studies are needed to define the predictive value of IGRAs. PMID- 17339620 TI - The declining number and variety of procedures done by general internists: a resurvey of members of the American College of Physicians. AB - BACKGROUND: A survey of general internist members of the American College of Physicians (ACP) in 1986 found that they did a large number and variety of procedures in their practices. Since then, changes in the practice of medicine, regulatory requirements, and availability of subspecialists may have affected the number and type of procedures done by internists. OBJECTIVE: To determine the number and types of procedures currently done by general internist members of the ACP compared with 1986. DESIGN: Mailed questionnaire. SETTING: National probability sample of general internists. PARTICIPANTS: Respondents to a national survey of 2500 general internist members of the ACP who were similar in characteristics to those who participated in the 1986 survey. Of the 1389 questionnaires that were returned, 990 were from general internists who had completed the survey. MEASUREMENTS: Responses to questions about procedures done and practice characteristics. RESULTS: The number and variety of procedures done by general internists has decreased dramatically. On average, the percentage of general internists doing each procedure now is less than half of that in 1986. The average number of different procedures done in practice decreased from 16 in 1986 to 7 in 2004. As in the 1986 survey, the number of procedures related strongly to personal and practice characteristics. Internists who practice in smaller towns and smaller hospitals do twice as many procedures on average as those in larger cities and larger hospitals. The number and variety of procedures done by internists also increased with greater time spent in total patient care. LIMITATIONS: The number and type of procedures were determined by self-reporting, not direct observation. CONCLUSIONS: Both the number and variety of procedures done by general internists have decreased considerably since 1986. As in the 1986 survey, general internists who practice in smaller cities and smaller hospitals and those who spend more hours in patient care perform more procedures. Recommendations and practices for internal medicine residency training in procedures should be reexamined in light of these changes. PMID- 17339621 TI - Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force recommendation statement. AB - This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendation and supporting scientific evidence on routine use of aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer. The complete information on which this statement is based, including evidence tables and references, is available in the accompanying articles in this issue and on the USPSTF Web site (http://www.preventiveservices.ahrq.gov). The USPSTF is redesigning its recommendation statement in response to feedback from primary care clinicians. The USPSTF plans to release, later in 2007, a new, updated recommendation statement that is easier to read and incorporates advances in USPSTF methodology. The recommendation statement below is an interim version that combines existing language and elements with a new format. Although the definitions of grades remain the same, other elements have been revised. PMID- 17339622 TI - The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. AB - BACKGROUND: Aspirin for prevention of colorectal cancer is controversial. PURPOSE: To examine the benefits and harms of aspirin chemoprevention. DATA SOURCES: MEDLINE, 1966 to December 2006; EMBASE, 1980 to April 2005; CENTRAL, Cochrane Collaboration's registry of clinical trials; Cochrane Database of Systematic Reviews. STUDY SELECTION: Two independent reviewers conducted multilevel screening to identify randomized, controlled trials (RCTs), case control studies, and cohort studies of aspirin chemoprophylaxis. For harms, systematic reviews were sought. DATA EXTRACTION: In duplicate, data were abstracted and checked and quality was assessed. DATA SYNTHESIS: Regular use of aspirin reduced the incidence of colonic adenomas in RCTs (relative risk [RR], 0.82 [95% CI, 0.7 to 0.95]), case-control studies (RR, 0.87 [CI, 0.77 to 0.98]), and cohort studies (RR, 0.72 [CI, 0.61 to 0.85]). In cohort studies, regular use of aspirin was associated with RR reductions of 22% for incidence of colorectal cancer. Two RCTs of low-dose aspirin failed to show a protective effect. Data for colorectal cancer mortality were limited. Benefits from chemoprevention were more evident when aspirin was used at a high dose and for periods longer than 10 years. Aspirin use was associated with a dose-related increase in incidence of gastrointestinal complications. LIMITATIONS: Important clinical and methodological heterogeneity in the definitions of regular use, dose, and duration of use of aspirin necessitated careful grouping for analysis. CONCLUSIONS: Aspirin appears to be effective at reducing the incidence of colonic adenoma and colorectal cancer, especially if used in high doses for more than 10 years. However, the possible harms of such a practice require careful consideration. Further evaluation of the cost-effectiveness of chemoprevention compared with, and in combination with, a screening strategy is required. PMID- 17339623 TI - Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. AB - PURPOSE: To examine the benefits and harms of nonaspirin (non-ASA) nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX-2) inhibitors for the prevention of colorectal cancer (CRC) and adenoma. DATA SOURCES: MEDLINE (1966 to 2006), EMBASE (1980 to 2006), Cochrane Central Register of Controlled Trials, Cochrane Collaboration's registry of clinical trials, Cochrane Database of Systematic Reviews. STUDY SELECTION: Randomized, controlled trials and case control and cohort studies of the effectiveness of NSAIDs for the prevention of CRC and colorectal adenoma were identified by multilevel screening by 2 independent reviewers. Systematic reviews of harms were sought. DATA EXTRACTION: Data abstraction, checking, and quality assessment were completed in duplicate. DATA SYNTHESIS: A single cohort study showed no effect of non-ASA NSAIDs on death due to CRC. Colorectal cancer incidence was reduced with non-ASA NSAIDs in cohort studies (relative risk, 0.61 [95% CI, 0.48 to 0.77]) and case-control studies (relative risk, 0.70 [CI, 0.63 to 0.78]). Colorectal adenoma incidence was also reduced with non-ASA NSAID use in cohort studies (relative risk, 0.64 [CI, 0.48 to 0.85]) and case-control studies (relative risk, 0.54 [CI, 0.4 to 0.74]) and by COX-2 inhibitors in randomized, controlled trials (relative risk, 0.72 [CI, 0.68 to 0.77]). The ulcer complication rate associated with non-ASA NSAIDs is 1.5% per year. Compared with non-ASA NSAIDs, COX-2 inhibitors reduce this risk but, in multiyear use, have a higher ulcer complication rate than placebo. Cyclooxygenase 2 inhibitors and nonnaproxen NSAIDs increase the risk for serious cardiovascular events (relative risk, 1.86 [CI, 1.33 to 2.59] for COX-2 inhibitors vs. placebo). LIMITATIONS: Heterogeneity in the dose, duration and frequency of use necessitated careful grouping for analysis. CONCLUSIONS: Cyclooxygenase-2 inhibitors and NSAIDs reduce the incidence of colonic adenomas. Nonsteroidal anti inflammatory drugs also reduce the incidence of CRC. However, these agents are associated with important cardiovascular events and gastrointestinal harms. The balance of benefits to risk does not favor chemoprevention in average-risk individuals. PMID- 17339624 TI - Anxiety disorders: efficient screening is the first step in improving outcomes. PMID- 17339625 TI - What procedures should internists do? PMID- 17339626 TI - The effect of polyphenols in olive oil on heart disease risk factors. PMID- 17339627 TI - The effect of polyphenols in olive oil on heart disease risk factors. PMID- 17339628 TI - Metronidazole-induced aseptic meningitis during Helicobacter pylori eradication therapy. PMID- 17339629 TI - Radiographic appearance of primary tuberculosis. PMID- 17339631 TI - Virus-derived platforms for visualizing protein associations inside cells. AB - Protein-protein associations are vital to cellular functions. Here we describe a helpful new method to demonstrate protein-protein associations inside cells based on the capacity of orthoreovirus protein muNS to form large cytoplasmic inclusions, easily visualized by light microscopy, and to recruit other proteins to these structures in a specific manner. We introduce this technology by the identification of a sixth orthoreovirus protein, RNA-dependent RNA polymerase lambda3, that was recruited to the structures through an association with muNS. We then established the broader utility of this technology by using a truncated, fluorescently tagged form of muNS as a fusion platform to present the mammalian tumor suppressor p53, which strongly recruited its known interactor simian virus 40 large T antigen to the muNS-derived structures. In both examples, we further localized a region of the recruited protein that is key to its recruitment. Using either endogenous p53 or a second fluorescently tagged fusion of p53 with the rotavirus NSP5 protein, we demonstrated p53 oligomerization as well as p53 association with another of its cellular interaction partners, the CREB-binding proteins, within the inclusions. Furthermore using the p53-fused fluorescent muNS platform in conjunction with three-color microscopy, we identified a ternary complex comprising p53, simian virus 40 large T antigen, and retinoblastoma protein. The new method is technically simple, uses commonly available resources, and is adaptable to high throughput formats. PMID- 17339632 TI - Compositional protein analysis of high density lipoproteins in hypercholesterolemia by shotgun LC-MS/MS and probabilistic peptide scoring. AB - A protein of a biological sample is usually quantified by immunological techniques based on antibodies. Mass spectrometry offers alternative approaches that are not dependent on antibody affinity and avidity, protein isoforms, quaternary structures, or steric hindrance of antibody-antigen recognition in case of multiprotein complexes. One approach is the use of stable isotope-labeled internal standards; another is the direct exploitation of mass spectrometric signals recorded by LC-MS/MS analysis of protein digests. Here we assessed the peptide match score summation index based on probabilistic peptide scores calculated by the PHENYX protein identification engine for absolute protein quantification in accordance with the protein abundance index as proposed by Mann and co-workers (Rappsilber, J., Ryder, U., Lamond, A. I., and Mann, M. (2002) Large-scale proteomic analysis of the human spliceosome. Genome Res. 12, 1231 1245). Using synthetic protein mixtures, we demonstrated that this approach works well, although proteins can have different response factors. Applied to high density lipoproteins (HDLs), this new approach compared favorably to alternative protein quantitation methods like UV detection of protein peaks separated by capillary electrophoresis or quantitation of protein spots on SDS-PAGE. We compared the protein composition of a well defined HDL density class isolated from plasma of seven hypercholesterolemia subjects having low or high HDL cholesterol with HDL from nine normolipidemia subjects. The quantitative protein patterns distinguished individuals according to the corresponding concentration and distribution of cholesterol from serum lipid measurements of the same samples and revealed that hypercholesterolemia in unrelated individuals is the result of different deficiencies. The presented approach is complementary to HDL lipid analysis; does not rely on complicated sample treatment, e.g. chemical reactions, or antibodies; and can be used for projective clinical studies of larger patient groups. PMID- 17339633 TI - Proteomics analysis of human coronary atherosclerotic plaque: a feasibility study of direct tissue proteomics by liquid chromatography and tandem mass spectrometry. AB - Cardiovascular disease presents significant variations in human populations with respect to the atherosclerotic plaque progression, inflammation, thrombosis, and rupture. To gain a more comprehensive picture of the pathogenic mechanism of atherosclerosis and the variations seen in patients, efficient methods to identify proteins from the normal and diseased arteries need to be developed. To accomplish this goal, we tested the feasibility and efficiency of protein identification by a recently developed method, termed direct tissue proteomics (DTP). We analyzed frozen and paraformaldehyde-fixed archival coronary arteries with the DTP method. We also validated the distinct expression of four proteins by immunohistochemistry. In addition, we demonstrated the compatibility of the DTP method with laser capture microdissection and the possibility of monitoring specific cytokines and growth factors by the absolute quantification of abundance method. Major findings from this feasibility study are that 1) DTP can be used to efficiently identify proteins from paraformaldehyde-fixed, paraffin-embedded, and frozen coronary arteries; 2) approximately twice the number of proteins were identified from the frozen sections when compared with the paraformaldehyde-fixed sections; 3) laser capture microdissection is compatible with DTP; and 4) detection of low abundance cytokines and growth factors in the coronary arteries required selective reaction monitoring experiments coupled to absolute quantification of abundance. The analysis of 35 human coronary atherosclerotic samples allowed identification of a total of 806 proteins. The present study provides the first large scale proteomics map of human coronary atherosclerotic plaques. PMID- 17339634 TI - Multiple hypothesis testing to detect lineages under positive selection that affects only a few sites. AB - Detection of positive Darwinian selection has become ever more important with the rapid growth of genomic data sets. Recent branch-site models of codon substitution account for variation of selective pressure over branches on the tree and across sites in the sequence and provide a means to detect short episodes of molecular adaptation affecting just a few sites. In likelihood ratio tests based on such models, the branches to be tested for positive selection have to be specified a priori. In the absence of a biological hypothesis to designate so-called foreground branches, one may test many branches, but a correction for multiple testing becomes necessary. In this paper, we employ computer simulation to evaluate the performance of 6 multiple test correction procedures when the branch-site models are used to test every branch on the phylogeny for positive selection. Four of the methods control the familywise error rates (FWERs), whereas the other 2 control the false discovery rate (FDR). We found that all correction procedures achieved acceptable FWER except for extremely divergent sequences and serious model violations, when the test may become unreliable. The power of the test to detect positive selection is influenced by the strength of selection and the sequence divergence, with the highest power observed at intermediate divergences. The 4 correction procedures that control the FWER had similar power. We recommend Rom's procedure for its slightly higher power, but the simple Bonferroni correction is useable as well. The 2 correction procedures that control the FDR had slightly more power and also higher FWER. We demonstrate the multiple test procedures by analyzing gene sequences from the extracellular domain of the cluster of differentiation 2 (CD2) gene from 10 mammalian species. Both our simulation and real data analysis suggest that the multiple test procedures are useful when multiple branches have to be tested on the same data set. PMID- 17339635 TI - PFMAGO, a MAGO NASHI-like factor, interacts with the MADS-domain protein MPF2 from Physalis floridana. AB - MADS-domain proteins serve as regulators of plant development and often form dimers and higher order complexes to function. Heterotopic expression of MPF2, a MADS-box gene, in reproductive tissues is a key component in the evolution of the inflated calyx syndrome in Physalis, but RNAi studies demonstrate that MPF2 has also acquired a role in male fertility in Physalis floridana. Using the yeast 2 hybrid system, we have now identified numerous MPF2-interacting MADS-domain proteins from Physalis, including homologs of SOC1, AP1, SEP1, SEP3, AG, and AGL6. Among the many non-MADS-domain proteins recovered was a homolog of MAGO NASHI, a highly conserved RNA-binding protein known to be involved in many developmental processes including germ cell differentiation. Two MAGO genes, termed P. floridana mago nashi1 (PFMAGO1) and PFMAGO2, were isolated from P. floridana. Both copies were found to be coexpressed in leaves, fruits, and, albeit at lower level, also in roots, stems, and flowers. DNA sequence analysis revealed that, although the coding sequences of the 2 genes are highly conserved, they differ substantially in their intron and promoter sequences. Two-hybrid screening of a Physalis expression library with both PFMAGO1 and PFMAGO2 as baits yielded numerous gene products, including an Y14-like protein. Y14 is an RNA binding protein that forms part of various "gene expression machines." The function of MPF2 and 2 PFMAGO proteins in ensuring male fertility and evolution of calyx development in Physalis is discussed. PMID- 17339636 TI - Evidence for a population expansion in the West Nile virus vector Culex tarsalis. AB - Population genetic structure of the West Nile Virus vector Culex tarsalis was investigated in 5 states in the western United States using 5 microsatellite loci and a fragment of the mitochondrial reduced form of nicotinamide adenine dinucleotide dehydrogenase 4 (ND4) gene. ND4 sequence analysis revealed a lack of isolation by distance, panmixia across all populations, an excess of rare haplotypes, and a star-like phylogeny. Microsatellites revealed moderate genetic differentiation and isolation by distance, with the largest genetic distance occurring between populations in southern California and New Mexico (F(ST) = 0.146). Clustering analysis and analysis of molecular variance on microsatellite data indicated the presence of 3 broad population clusters. Mismatch distributions and site-frequency spectra derived from mitochondrial ND4 sequences displayed pattern's characteristic of population expansion. Fu and Li's D* and F*, Fu's F(S), and Tajima's D statistics performed on ND4 sequences all revealed significant, negative deviations from mutation-drift equilibrium. Microsatellite based multilocus heterozygosity tests showed evidence of range expansion in the majority of populations. Our results suggest that C. tarsalis underwent a range expansion across the western United States within the last 375,000-560,000 years, which may have been associated with Pleistocene glaciation events that occurred in the midwestern and western United States between 350,000 and 1 MYA. PMID- 17339637 TI - Adult neurogenesis in the hippocampus of long-lived mice during aging. AB - Ames dwarf mice live considerably longer than normal animals, exhibit apparently normal cognitive functions, and maintain them into advanced age. Neurogenesis occurs throughout adult life span in the dentate gyrus of mammalian hippocampus and has been suggested to play an important role in cognitive function. We now report that the total number of bromodeoxyuridine (BrdU)-labeled cells in this brain region in aged Ames dwarf mice was not different from that in aged normal mice, whereas the fraction of newly generated neurons was significantly increased by monitoring BrdU labeling and cell marker expression. Evidence of activation of anti-apoptosis signal transduction cascade was also found in the hippocampus of aged dwarf mice. Together with previous findings, the results may suggest that an increase in hippocampal insulin-like growth factor-I protein expression and subsequent activation of antiapoptotic signaling might contribute to survival of newly born neurons and subsequently to the delay of cognitive loss during aging in these long-lived dwarf mice. PMID- 17339639 TI - Impact of aging on rat bone marrow-derived stem cell chondrogenesis. AB - Damaged articular cartilage rarely heals or regenerates in middle-aged and elderly adults, suggesting that the chondrogenic potential of mesenchymal stem cells declines with age. To test this hypothesis, we measured the responses of rat bone marrow-derived mesenchymal stem cells (BMSCs) to chondrogenic induction in vitro. BMSCs from immature rats (1 week old), young adult rats (12 weeks old), and old adult rats (1 year old) were analyzed for cartilage extracellular matrix (ECM) production. Histologic analysis showed strong cartilage ECM formation by BMSCs from 1-week-old rats, but not by BMSCs from 12-week-old or 1-year-old rats. Real-time polymerase chain reaction revealed age-related declines in messenger RNA encoding type II collagen, aggrecan, and link protein, three major cartilage ECM components. Microarray analysis indicated significant age-related differences in the expression of genes that influence cartilage ECM formation. These findings support the hypothesis that the chondrogenic potential of mesenchymal stem cells declines with age. PMID- 17339638 TI - A demographic analysis of the fitness cost of extended longevity in Caenorhabditis elegans. AB - We monitored survival and reproduction of 1000 individuals of Caenorhabditis elegans wild type (N2) and 800 individuals of clk-1 and daf-2, and used biodemographic analysis to address fitness as the integrative consequence of the entire age-specific schedules of survival and reproduction. Relative to N2, the mutants clk-1 and daf-2 extended average life span by 27% and 111%, respectively, but reduced net reproductive rate by 44% and 18%. The net result of differences in survival and fertility was a significant differential in fitness, with both clk-1 (lambda = 2.74) and daf-2 (lambda = 3.78) at a disadvantage relative to N2 (lambda = 3.85). Demographic life table response experiment (LTRE) analysis revealed that the fitness differentials were due to negative effects in mutants on reproduction in the first 6-7 days of life. Fitness costs in clk-1 and daf-2 of C. elegans are consistent with the theory of antagonistic pleiotropy for the evolution of senescence. PMID- 17339640 TI - An analysis of the relationship between metabolism, developmental schedules, and longevity using phylogenetic independent contrasts. AB - Comparative studies of aging are often difficult to interpret because of the different factors that tend to correlate with longevity. We used the AnAge database to study these factors, particularly metabolism and developmental schedules, previously associated with longevity in vertebrate species. Our results show that, after correcting for body mass and phylogeny, basal metabolic rate does not correlate with longevity in eutherians or birds, although it negatively correlates with marsupial longevity and time to maturity. We confirm the idea that age at maturity is typically proportional to adult life span, and show that mammals that live longer for their body size, such as bats and primates, also tend to have a longer developmental time for their body size. Lastly, postnatal growth rates were negatively correlated with adult life span in mammals but not in birds. Our work provides a detailed view of factors related to species longevity with implications for how comparative studies of aging are interpreted. PMID- 17339641 TI - Exploring the hierarchy of mobility performance in high-functioning older women. AB - BACKGROUND: Preventing mobility disability depends on matching interventions to individual needs. The purpose of this study is to improve targeting by determining whether mobility performance is associated with, and predicts, mobility disability hierarchically. The hypothesis is that poorer performance tested by more demanding tasks is more strongly associated with current and future mobility "limitation" (self-reported task modification or difficulty) than is that tested by less demanding tasks, in a graded manner. METHODS: Data come from the Women's Health and Aging Study II (n = 436) at baseline and at 36-month follow-up. Logistic and multinomial regression models examined associations between performance on mobility tests and reported limitation in walking one-half mile, adjusting for risk factors for disability. RESULTS: We found that 76.6% of prevalent and 88.4% of new-onset self-reported limitation fit within the hypothesized hierarchical pattern. The estimated strength of association between a decrement in lower extremity performance and reported limitation increased with task demand for the primary outcome, reported limitation in walking one-half mile. For example, the odds ratios for prevalent report of walking limitation, versus no limitation, for 10% lower performance walking, dressing, repeating chair stands, and climbing, respectively, were 1.05 (95% confidence interval, 0.97-1.17), 1.08 (1.00-1.16), 1.15 (1.06-1.25), and 1.22 (1.12-1.33). CONCLUSIONS: This study partially supports the hypothesis that mobility performance tends to follow a hierarchical pattern. For studying mild mobility disability, walking speed may not be as useful as more demanding tests. Identifying declines in performance through more demanding tests such as climbing should improve the ability to target preventive interventions to individuals at risk of mild mobility decline within a high-functioning population. PMID- 17339642 TI - Association between psychomotor activity delirium subtypes and mortality among newly admitted post-acute facility patients. AB - BACKGROUND: Delirium is common among hospitalized elders and may persist for months. Therefore, the adverse impact of delirium on independence often occurs in the post acute care (PAC) setting. The effect of psychomotor subtypes on delirium remains uncertain. The purpose of this study is to examine the association between psychomotor activity delirium subtypes and 1-year mortality among 457 newly admitted delirious PAC patients. METHODS: Patients were screened for delirium on admission to PAC facilities after an acute hospitalization, and patients with "Confusion Assessment Method"-defined delirium were enrolled. Psychomotor activity was assessed using the Memorial Delirium Assessment Scale, and patients were classified as to their delirium subtype (hyperactive, hypoactive, mixed, or normal). One-year mortality data were obtained from the National Death Index. A Kaplan-Meier survival analysis and a proportional hazards analysis using indicator (dummy) variables with normal psychomotor activity as the referent were performed. RESULTS: The normal psychomotor activity group had the lowest 1-year mortality rate, followed by the hyperactive, mixed, then hypoactive groups in increasing order. Independent of age, gender, comorbidity, dementia, and delirium severity, hypoactive patients were 1.60 (95% confidence interval [CI], 1.09-2.35) times more likely to die during the 1-year follow-up period than were patients with normal psychomotor activity. The hyperactive (hazard ratio = 1.30; 95% CI, 0.73-2.31) and mixed (hazard ratio = 1.25; 95% CI, 0.72-2.17) psychomotor groups had nonsignificant elevated risks relative to the normal psychomotor behavior group. CONCLUSIONS: All three psychomotor disturbance subtypes had an elevated risk of dying during the 1-year follow-up relative to the normal psychomotor group, though the hypoactive group had the highest mortality risk and was the only group with a statistically significantly elevated risk relative to the normal group. PMID- 17339643 TI - Alarming rise in the number and incidence of fall-induced cervical spine injuries among older adults. AB - BACKGROUND: Although fall-induced injuries among older adults are said to be a major public health concern in modern societies with aging populations, reliable epidemiologic information on their secular trends is limited. METHODS: We determined the current trend in the number and incidence (per 100,000 persons) of fall-induced severe cervical spine injuries (fracture, cord injury, or both) of older adults in Finland, a European Union country with a well-defined white population of 5.2 million, by taking into account all persons aged 50 years or older who were admitted to all Finnish hospitals for primary treatment of such injury in 1970-2004. Similar patients aged 20-49 years served as a reference group. RESULTS: The number and raw incidence of fall-induced cervical spine injury among Finns aged 50 years or older rose considerably between the years 1970 and 2004, from 59 (number) and 5.2 (incidence) in 1970 to 228 and 12.0 in 2004. The relative increases were 286% and 131%, respectively. Throughout the study period, the age-standardized incidence of injury was higher in men than women, and showed a clear increase in both sexes in 1970-2004 from 8.5 to 17.4 in men (105% increase), and from 2.8 to 6.4 in women (129% increase). A similar finding was observed in the age-specific incidences of the study group. In the reference group, the annual number and incidence of injury decreased slightly over time. Assuming that the observed increase in the age-standardized or age specific injury incidence continues in Finns aged 50 years or older and the size of this population increases as predicted, the annual number of fall-induced cervical spine injuries in this population will be about 100% higher in the year 2030 (about 400 injuries annually) than it was during 2000-2004 (about 200 injuries annually). CONCLUSIONS: In Finnish persons aged 50 years or older, the number of fall-induced severe cervical spine injuries seems to show an alarming rise with a rate that cannot be explained merely by demographic changes. The finding underscores an increasing influence of falls on health and well-being of our older adults; therefore, wide-scale fall-prevention measures should be urgently adopted to control this development. PMID- 17339644 TI - Arthritis-specific health beliefs related to aging among older male patients with knee and/or hip osteoarthritis. AB - BACKGROUND: Disease-specific beliefs may impact patients' perceptions of the efficacy of various treatment options, thus, it is important to understand these beliefs. We examined the relationship between patients' demographic characteristics and arthritis-specific beliefs related to aging. METHODS: We performed a cross-sectional survey of 591 elderly primary care patients, who had symptomatic osteoarthritis (OA) of the knee and/or hip, at the Louis Stokes VA Medical Center in Cleveland, Ohio. Data were collected on age, race, educational level, income, and whether patients agreed or disagreed with four statements regarding aging and arthritis. We also assessed OA symptom severity using the Western Ontario McMaster Universities Index (WOMAC) and depressive symptoms using the Geriatric Depression Scale. We used logistic regression analyses to examine relationships between patients' age, race, and educational level and arthritis specific health beliefs, while adjusting for OA symptom severity, radiographic confirmation of OA, OA joint burden, depressive symptoms, and income. RESULTS: Patients 70 years old or older, as compared to patients 50-59 years old, were more likely to believe that: arthritis is a natural part of growing old; people should expect that when they get older, they won't be able to walk as well, and people should expect to live with pain as they grow older. CONCLUSION: Among older, male veterans, health beliefs regarding the relationship between aging and arthritis vary by age. Clinicians should consider these differences when discussing treatment strategies with their patients with knee and/or hip OA. PMID- 17339646 TI - Methylenetetrahydrofolate reductase 677C>T and methionine synthase 2756A>G mutations: no impact on survival, cognitive functioning, or cognitive decline in nonagenarians. AB - BACKGROUND: Several reports have shown an association between homocysteine, cognitive functioning, and survival among the oldest-old. Two common polymorphisms in the genes coding for methylenetetrahydrofolate reductase (MTHFR 677C>T) and methionine synthase (MTR 2756A>G) have an impact on plasma homocysteine level. METHODS: We examined the effect of the MTHFR 677C>T and MTR 2756A>G genotypes on baseline cognitive functioning, cognitive decline over 5 years measured in three assessments, and survival in a population-based cohort of 1581 nonagenarians. Cognitive functioning was assessed by using the Mini-Mental State Examination (MMSE) and five brief cognitive tests (cognitive composite). RESULTS: There are no differences in MMSE score (p =.83) or in cognitive composite (p =.56) at intake as a function of genotype tested by analysis of variance, whereas sex and social group have a impact on MMSE (p < or =.03), and social group on the cognitive composite (p <.01). The mean MMSE was lower for women than for men. However, considering the group participating in all three assessments, there were no sex-related differences in MMSE (p =.34). The cognitive decline in the group participating in all three assessments was investigated using regression models for the relationship between cognitive performance and genotype, age, sex, and social group and revealed no significant difference. Furthermore, the MTHFR 677T and MTR 2756A heterozygous and homozygous genotype had no significant impact on survival, with hazard ratios of 1.05 (95% confidence interval [CI], 0.93-1.17), 0.93 (95% CI, 0.77-1.14), 1.05 (95% CI, 0.94-1.18), and 0.97 (95% CI, 0.74-1.28). CONCLUSIONS: MTHFR and MTR genotypes are not associated with cognitive functioning, cognitive decline, or survival among nonagenarians. PMID- 17339645 TI - Perception of unmet basic needs as a predictor of depressive symptoms among community-dwelling older adults. AB - BACKGROUND: In previous studies we found that, among older adults (>64 years), perception that basic needs were not being met increased mortality risk and risk for functional decline. In this study, we determined, controlling for reported income and functional status, if perceived inadequate basic needs predicted depressive symptoms. METHODS: Repeated-measures analysis was used to determine, during three intervals in a 10-year longitudinal study (the Duke Established Populations for Epidemiologic Studies of the Elderly, n = 4162 at baseline), if perceived inadequate basic needs at the beginning of each interval predicted more depressive symptoms at the end of the interval. We included time invariant covariates known to be associated with depressive symptoms--age, sex, race, and education. We also included time-varying covariates at the beginning of the three intervals--income, cognitive status, functional status, depressive symptoms, and interval. RESULTS: In the repeated-measures controlled analyses, the perception of inadequate basic needs was a highly significant predictor of future depressive symptoms (p <.0001). Race, education, baseline depression, baseline function, interval, and income were also significant predictors of depression. The interaction between interval and depression was not significant. CONCLUSIONS: The perception that one's basic needs are not being met predicted future depressive symptoms in a highly controlled analysis. These results suggest that perception of inadequate basic needs, even when income and other known correlates of depression are controlled, is a strong predictor of future depressive symptoms. PMID- 17339647 TI - Absence of relationship between MTTP haplotypes and longevity. AB - BACKGROUND: Polymorphisms for the microsomal triglyceride transfer protein (MTTP) gene have been associated with longevity and with lower risk for cardiovascular mortality. However, the association of MTTP with longevity has been contested in a large German collection of nonagenarians and centenarians. METHODS: We made a detailed characterization of MTTP haplotype carrier status in a cohort of 1398 old men and women (mean age 78 years) and a population-based cohort (n = 777) of younger controls (mean age 40 years) in Oxford, England. RESULTS: There were no significant differences in haplotypes for MTTP gene between the younger and older age groups. CONCLUSION: This study, which adopted a more detailed genetic analysis of the MTTP gene in a large case-control study of older people provides reliable evidence against any significant association of the MTTP gene with longevity. PMID- 17339648 TI - Alpha-actinin-3 (ACTN3) R577X polymorphism influences knee extensor peak power response to strength training in older men and women. AB - BACKGROUND: The alpha-actinin-3 (ACTN3) R577X polymorphism has been associated with muscle power performance in cross-sectional studies. METHODS: We examined baseline knee extensor concentric peak power (PP) and PP change with approximately 10 weeks of unilateral knee extensor strength training (ST) using air-powered resistance machines in 71 older men (65 [standard deviation = 8] years) and 86 older women (64 [standard deviation = 9] years). RESULTS: At baseline in women, the XX genotype group had an absolute (same resistance) PP that was higher than the RR (p =.005) and RX genotype groups (p =.02). The women XX group also had a relative (70% of one-repetition maximum [1-RM]) PP that was higher than that in the RR (p =.002) and RX groups (p =.008). No differences in baseline absolute or relative PP were observed between ACTN3 genotype groups in men. In men, absolute PP change with ST in the RR (n = 16) group approached a significantly higher value than in the XX group (n = 9; p =.07). In women, relative PP change with ST in the RR group (n = 16) was higher than in the XX group (n = 17; p =.02). CONCLUSIONS: The results indicate that the ACTN3 R577X polymorphism influences the response of quadriceps muscle power to ST in older adults. PMID- 17339649 TI - Alcoholic beverage preference, 29-year mortality, and quality of life in men in old age. AB - BACKGROUND: Harms of excessive alcohol consumption are obvious, but moderate wine consumption is frequently advocated for prevention of cardiovascular diseases. We compared 29-year mortality and quality of life in old age by alcoholic beverage preference (beer, wine, or spirits) in a cohort of men whose socioeconomic status was similar in their adult life. METHODS: In 1974, cardiovascular risk factors and beverage preference were assessed in 2468 businessmen and executives aged 40 55 years. Of them, 131 did not use alcohol, 455 did not report a single preference, and 694, 251, and 937 preferred beer, wine, and spirits, respectively. Quality of life with a RAND-36 Short Form (SF)-36 instrument was surveyed in 2000 in survivors. Mortality was retrieved from registers during the 29-year follow-up. RESULTS: Alcoholic beverage preference tracked well during the follow-up. Total alcohol consumption was not significantly different between preference groups. Men with wine preference had the lowest total mortality due to lower cardiovascular mortality. With the spirits group as the reference category and age, cardiovascular risk factors, and total alcohol consumption as covariates, wine drinkers had a 34% lower total mortality (relative risk 0.66; 95% confidence interval, 0.45-0.98); relative risk for beer preferers was 0.91 (95% confidence interval, 0.68-1.14). In 2000, wine preferers had the highest scores in all RAND-36 scales; general health (p =.007) and mental health (p =.01) were also significantly different. CONCLUSION: In this male cohort from the highest social class, wine preference was associated with lower mortality and better quality of life in old age. Mortality advantage was independent of overall alcohol consumption and cardiovascular risk factors, but contributing personal characteristics or early life differences cannot be excluded. PMID- 17339650 TI - Analysis of leakage in IRGA's leaf chambers of open gas exchange systems: quantification and its effects in photosynthesis parameterization. AB - The measurement of the response of net photosynthesis to leaf internal CO2 (i.e. A-Ci curves) is widely used for ecophysiological studies. Most studies did not consider CO2 exchange between the chamber and the surrounding air, especially at the two extremes of A-Ci curves, where large CO2 gradients are created, leading to erroneous estimations of A and Ci. A quantitative analysis of CO2 leakage in the chamber of a portable open gas exchange system (Li-6400, LI-COR Inc., NE, USA) was performed. In an empty chamber, the measured CO2 leakage was similar to that calculated using the manufacturer's equations. However, in the presence of a photosynthetically inactive leaf, the magnitude of leakage was substantially decreased, although still significant. These results, together with the analysis of the effects of chamber size, tightness, flow rate, and gasket material, suggest that the leakage is larger at the interface between the gaskets than through the gaskets. This differential leakage rate affects the parameterization by photosynthesis models. The magnitude of these errors was assessed in tobacco plants. The results showed that leakage results in a 10% overestimation of the leaf maximum capacity for carboxylation (Vc,max) and a 40% overestimation of day respiration (Rl). Using the manufacturer's equations resulted in larger, non realistic corrections of the true values. The photosynthetic response to CO2 concentrations at the chloroplast (i.e. A-Cc curves) was significantly less affected by leakage than A-Ci curves. Therefore, photosynthetic parameterization can be improved by: (i) correcting A and Ci values for chamber leakage estimated using a photosynthetically inactive leaf; and (ii) using A-Cc instead of A-Ci curves. PMID- 17339651 TI - OsMTN encodes a 5'-methylthioadenosine nucleosidase that is up-regulated during submergence-induced ethylene synthesis in rice (Oryza sativa L.). AB - Methylthioadenosine (MTA) is released as a by-product of S-adenosylmethionine (AdoMet)-dependent reactions central to ethylene, polyamine, or phytosiderophore biosynthesis. MTA is hydrolysed by methylthioadenosine nucleosidase (MTN; EC 3.2.2.16) into adenine and methylthioribose which is processed through the methionine (Met) cycle to produce a new molecule of AdoMet. In deepwater rice, submergence enhances ethylene biosynthesis, and ethylene in turn influences the methionine cycle through positive feedback regulation of the acireductone dioxygenase gene OsARD1. In rice, MTN is encoded by a single gene designated OsMTN. Recombinant OsMTN enzyme had a KM for MTA of 2.1 mM and accepted a wide array of 5' substitutions of the substrate. OsMTN also metabolized S adenosylhomocysteine (AdoHcy) with 15.9% the rate of MTA. OsMTN transcripts and OsMTN-specific activity increased slowly and in parallel upon submergence, indicating that regulation occurred mainly at the transcriptional level. Neither ethylene, MTA, nor Met regulated OsMTN expression. Analysis of steady-state metabolite levels showed that MTN activity was sufficiently high to prevent Met and AdoMet depletion during long-term ethylene biosynthesis. PMID- 17339652 TI - Functional characterization of MADS box genes involved in the determination of oil palm flower structure. AB - In order to study the molecular regulation of flower development in the monoecious species oil palm (Elaeis guineensis), cDNAs of 12 MADS box genes from this plant belonging to seven distinct subfamilies were previously isolated and characterized. Here studies carried out on five of these genes, each likely to be involved in floral morphogenesis: EgSQUA1 (SQUAMOSA subfamily); EgAGL2-1 (AGL2 subfamily); EgGLO2 (GLOBOSA subfamily); EgDEF1 (DEFICIENS subfamily); and EgAG2 (AGAMOUS subfamily), are described. In order to determine where and when in the plant these genes are likely to function, their spatial and temporal patterns of expression were studied during the development of male and female inflorescences, either of normal phenotype or displaying a homeotic flowering abnormality known as mantled. In parallel, the phenotypic effects of ectopically expressing these genes in transgenic Arabidopsis thaliana plants were analysed. The data suggest a broad conservation of floral homeotic gene functions between oil palm and previously described model species, although a few minor variations in the zones of activity of certain genes cannot be excluded. The data also indicate distinct molecular identities for the morphologically similar floral organs of whorls 1 and 2. They also reveal reduced expression of putative B, C/D, and E class genes in mantled flowers, which undergo a homeotic transformation comparable to B class mutants of model species. PMID- 17339653 TI - Genetic control of pungency in C. chinense via the Pun1 locus. AB - Capsaicin, the pungent principle in hot peppers, acts to deter mammals from consuming pungent pepper pods. Capsaicinoid biosynthesis is restricted to the genus Capsicum and results from the acylation of the aromatic compound, vanillylamine, with a branched-chain fatty acid. The presence of capsaicinoids is controlled by the Pun1 locus, which encodes a putative acyltransferase. In its homozygous recessive state, pun1/pun1, capsaicinoids are not produced by the pepper plant. HPLC analysis confirmed that capsaicinoids are only found in the interlocular septa of pungent pepper fruits. Immunolocalization studies showed that capsaicinoid biosynthesis is uniformly distributed across the epidermal cells of the interlocular septum. Capsaicinoids are secreted from glandular epidermal cells into subcuticular cavities that swell to form blisters along the epidermis. Blister development is positively associated with capsaicinoid accumulation and blisters are not present in non-pungent fruit. A genetic study was used to determine if the absence of blisters in non-pungent fruit acts independently of Pun1 to control pungency. Screening of non-pungent germplasm and genetic complementation tests identified a previously unknown recessive allele of Pun1, named pun1(2). Sequence analysis of pun1(2) revealed that a four base pair deletion results in a frameshift mutation and the predicted production of a truncated protein. Genetic analysis revealed that pun1(2) co-segregated exactly with the absence of blisters, non-pungency, and a reduced transcript accumulation of several genes involved in capsaicinoid biosynthesis. Collectively, these results establish that blister formation requires the Pun1 allele and that pun1(2) is a recessive allele from C. chinense that results in non-pungency. PMID- 17339654 TI - Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification. AB - Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1(+/+) mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In this study, we tested the hypothesis that apoC-I interferes with cellular FFA uptake independent of LPL activity. The cutaneous abnormalities of APOC1(+/+) mice were not affected after transplantation to wild type mice, indicating that locally produced apoC-I prevents lipid entry into the skin. Subsequent in vitro studies with apoC-I-deficient versus wild-type macrophages revealed that apoC-I reduced the cell association and subsequent esterification of [(3)H]oleic acid by approximately 35% (P < 0.05). We speculated that apoC-I binds FFA extracellularly, thereby preventing cell association of FFA. We showed that apoC-I was indeed able to mediate the binding of oleic acid to otherwise protein-free VLDL-like emulsion particles involving electrostatic interaction. We conclude that apoC-I binds FFA in the circulation, thereby reducing the availability of FFA for uptake by cells. This mechanism can serve as an additional mechanism behind the resistance to obesity and the cutaneous abnormalities of APOC1(+/+) mice. PMID- 17339658 TI - Transforming the U.S. child health system. AB - This paper presents a vision and rationale for reform of the U.S. child health system based on paradigmatic changes in the conceptualization of child health development. Reviewing well-known and well-documented accounts of how this system is under-performing, we suggest that a bold, well-defined, transformative, and long-term reform strategy is needed to address intractable problems in the underlying operating logic, organization, and financing of the current child health system. We conclude by considering an optimistic, long-term policy transformation agenda, building up emerging opportunities and changing realities in the United States and abroad. PMID- 17339659 TI - Chipping away at health: more on the relationship between income and child health. AB - Low-income children are in worse health than other children are. This paper explores the extent to which insults to health and activity limitations are responsible. In the most recent National Health Interview Survey (NHIS) data, low income children are more likely than other children to have virtually every measured chronic or acute condition and are more likely to be limited by these conditions. Mental health conditions are particularly common and limiting. But the higher incidence of measured conditions and limits does not explain all of the relationships between income and overall health status, which suggests that unmeasured illnesses and injuries are also involved. PMID- 17339660 TI - Reassessing how society prioritizes the health of young people. AB - A number of important health policy issues, such as the allocation of flu vaccines during a pandemic, require society to determine priorities across different age groups. Cost-effectiveness analysis (CEA) and related methods of economic evaluation are often useful for determining optimal resource allocations. Using the examples of recently evaluated vaccine interventions, we show that current methods of CEA are likely to under-value health interventions for young people, relative to societal preferences inferred from research on age preferences and the value of health over time. These findings demonstrate important considerations regarding how society distributes health resources across age groups. PMID- 17339662 TI - SCHIP at a crossroads: experiences to date and challenges ahead. AB - As reauthorization of the State Children's Health Insurance Program (SCHIP) looms, we examine the program's first decade and identify changes needed so that SCHIP can better serve its target population. We conclude that by many objective standards, SCHIP has been a success, but the challenge will be to maintain and build upon that success. Critical issues include the level and structure of federal funding; the continued problem of uninsurance among low-income children; the lack of information on quality, access, and costs; and whether SCHIP can serve as the foundation for addressing broader health care needs among low-income families. PMID- 17339663 TI - Medicaid at the ten-year anniversary of SCHIP: looking back and moving forward. AB - The adoption of the State Children's Health Insurance Program (SCHIP) in 1997 spurred widespread efforts to simplify and revitalize Medicaid coverage for children. To an extent often not recognized, these Medicaid improvements were a key factor behind much of the progress that has been made in covering low-income children: These children's uninsurance rate dropped from 22.3 percent in 1997 to 14.9 percent in 2005, and more than 70 percent of those gains can be attributed to Medicaid. The program, however, faces a number of issues that will need to be addressed if the country is to continue to make progress. PMID- 17339664 TI - Crossing the Medicaid-private insurance divide: the case of EPSDT. AB - Contained in the Deficit Reduction Act of 2005 is a provision that could greatly affect Medicaid's signature child health coverage standard, embodied since 1967 in the Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) benefit. Whether the core child health and developmental principles that have been EPSDT's touchstone for four decades will continue to guide Medicaid depends on whether and how these principles will be incorporated into states' coverage reforms. PMID- 17339665 TI - Universal coverage for children: alternatives, key issues, and political opportunities. AB - This paper describes four alternatives for expanding childhood insurance coverage, discusses key health policy issues, and assesses the political possibilities for enacting universal coverage. Alternatives are (1) a single federal child health program for all children; (2) a hybrid federal child health program (replacing Medicaid and the State Children's Health Insurance Program [SCHIP]), combined with employer coverage; (3) a new federal wraparound program for the uninsured (that keeps the existing Medicaid program); and (4) expansion of SCHIP. Key policy issues include the type of universal coverage, use of competing commercial health plans, financing, employer and individual mandates, and the definition of benefits. PMID- 17339666 TI - The moral case for covering children (and everyone else). AB - Before the crucial upcoming debate over reauthorization of the State Children's Health Insurance Program (SCHIP) and all of the 10,000 general health reform questions that this discussion will engender, we should consider one fundamental moral question, for our answer will reveal the kinds of policies we actually want to pursue: Who should be allowed to sit at our health care table of plenty? This essay sketches an answer to this question, drawing on the literature of various faith traditions as well as recent health services research. The short answer is: Everyone, but poor kids have a special place reserved for them. PMID- 17339668 TI - Health at school: a hidden health care system emerges from the shadows. AB - A vast array of child health professionals-99,000 counselors; 56,000 nurses; 30,000 school psychologists; 15,000 social workers; and smaller numbers of dental hygienists, dentists, physicians, and substance abuse counselors-provide care to children and adolescents at school. However, most thought leaders in child health know little about this "hidden" system of care or are skeptical about its capacity to contribute to children's well-being. Increased interest in prevention and chronic disease management, powered by escalating concern about childhood overweight, might end the isolation of school health programs and link them more effectively to community-based prevention programs and health care services. PMID- 17339669 TI - Medicaid: health promotion and disease prevention for school readiness. AB - Medicaid's child health program, Early and Periodic Screening, Diagnosis, and Treatment (EPSDT), emphasizes health promotion and disease prevention as vehicles to ensure that children are ready for school and able to succeed in life. Required components of preventive care can be mapped to specific health outcomes that are important attributes of school readiness and prerequisites for educational success. The federal government and states can take specific action to assure that children receive all of the health care services, including preventive services, necessary to promote their optimal health and development and, thus, to maximize their future productivity. PMID- 17339670 TI - Health plans' role in preventing overweight in children and adolescents. AB - The increasing prevalence of overweight children and adolescents in the United States threatens the well-being of a vast segment of this population. This paper examines how U.S. health plans can promote evidence-based behavioral-change strategies by directly intervening in medical settings and by supporting efforts to modify the environments in which young people live, study, and play. We describe a variety of innovative initiatives launched in recent years by health plans to address overweight among children and adolescents. Despite gaps in the evidence base, enough is now known to support aggressive steps to control this important public health problem. PMID- 17339671 TI - Childhood obesity: what's health care policy got to do with it? AB - The health care industry must acknowledge its critical role in addressing childhood obesity. All components of the industry--payers, plans, and providers- must act based on the best available evidence. This evidence now points to promoting breastfeeding and increased physical activity, decreased television time, and decreased consumption of sugar-sweetened beverages; the use of more effective counseling techniques; and linking practice and community-based strategies around a common message. Policies in support of these changes include reimbursement for counseling and community efforts; training; incentives; and support for traditional and pragmatic research, the latter including sharing outcomes using common metrics across programs. PMID- 17339672 TI - A historically based thought experiment: meeting new challenges for children's health and well-being. AB - In fall 2004 we proposed a way to use the lessons of the past to inform U.S. children's health policy, given the increasingly critical needs of children in this country. Continuing in that tradition and beyond, we describe here the founding and early work of the Children's Bureau and consider how it might be a model for the near future. We propose the creation of a Department of Children's Affairs (DoCA), which would unite the various federal agency-level initiatives aimed at children's health and well-being, much as the Department of Homeland Security did for terrorism defense activities after 9/11. PMID- 17339673 TI - The global market for ADHD medications. AB - Little is known about the global use and cost of medications for attention deficit hyperactivity disorder (ADHD). Global use of ADHD medications rose threefold from 1993 through 2003, whereas global spending (2.4 billion US dollars in 2003) rose ninefold, adjusting for inflation. Per capita gross domestic product (GDP) robustly predicted use across countries, but the United States, Canada, and Australia showed significantly higher-than-predicted use. Use and spending grew in both developed and developing countries, but spending growth was concentrated in developed countries, which adopted more costly, long-acting formulations. Promoting optimal prescription and monitoring should be a priority. PMID- 17339674 TI - Reducing infant mortality in Chile: success in two phases. AB - Latin America, and especially Chile, has done well in reducing infant mortality, with rates of around twenty-five per thousand live births. There are two clear phases of declining mortality: one largely influenced by poverty reduction, primary health care, and environmental and demographic factors; and a second one more sensitive to focused health care interventions. In 2000 Chile reached 8.9 infant deaths per 1,000, using interventions that represent an increase in the provision of services related to perinatal risks, acute respiratory diseases, congenital heart conditions, and certain vaccine-preventable infections. Chile, with per capita income near 5,000 US dollars in 2000, has infant mortality that compares with that of wealthier countries. PMID- 17339675 TI - Beyond medical care: how health systems can address children's needs through health promotion strategies. AB - This paper describes an innovative approach that integrates community-based health promotion and disease prevention into a well-established pediatric medical care system. System components include a population-level focus in multiple service sectors, community coalitions, knowledge dissemination, and social marketing. The combination of these components is intended to bring about widespread changes in health/social policy and professional practice, which, in turn, should improve health behavior and outcomes. Early lessons are discussed. PMID- 17339676 TI - Poor health kills small business: illness and microenterprises in South Africa. AB - Small businesses contribute almost 50 percent of total employment and 30 percent of gross domestic product in South Africa, but the impact of poor health and AIDS on these businesses is poorly documented. Using three waves of longitudinal data from predominantly African neighborhoods in peri-urban Durban, South Africa, this project investigates the connections between the health of the owner of a micro- and small enterprise (MSE) and the MSE's growth, survival, or exit. The results show that poor baseline health and declines in health over time are both significantly associated with subsequent business closure. PMID- 17339677 TI - Confidentiality laws and secrecy in medical research: improving public access to data on drug safety. AB - Pharmaceutical manufacturers have long considered results collected from drugs' clinical trials to be confidential information or trade secrets, even after submission to the Food and Drug Administration (FDA). We describe FDA policies regarding disclosure of clinical trial data and evaluate how courts have interpreted the Freedom of Information Act in cases seeking access to unreleased information. Recent examples of approved drugs later found to have dangerous side effects show the importance of complete dissemination of safety information. We suggest regulatory and legislative policy changes regarding how the FDA handles confidential information that can improve understanding of the risks of prescription drugs. PMID- 17339678 TI - General internists' views on pay-for-performance and public reporting of quality scores: a national survey. AB - Very little is known about rank-and-file physicians' views on pay-for-performance (P4P) and public reporting. In a national survey of general internists, we found strong potential support for financial incentives for quality, but less support for public reporting. Large majorities of respondents stated that these programs will result in physicians' avoiding high-risk patients and will divert attention from important types of care for which quality is not measured. Public and private policymakers might avoid a physician backlash and better succeed at improving health care quality if they consider these concerns when designing P4P and public reporting programs. PMID- 17339679 TI - Impact of state tort reforms on physician malpractice payments. AB - State and federal initiatives to enact medical malpractice tort reforms lack an empirical basis for understanding how reforms might affect malpractice premiums and costs. This paper ranks each state's tort provisions, uses multivariate analysis to measure the effects of strong versus weak enactments on paid claims, and identifies tort law patterns associated with high and low claims frequency and payment levels. Our results suggest that (1) the size and number of medical malpractice payments are affected by only some tort reforms; and (2) the pattern of reforms differs between states with high versus low levels of claims or payments. PMID- 17339680 TI - The edge of the known world. PMID- 17339681 TI - When paper is the enemy. PMID- 17339682 TI - How stable is medicaid coverage for children? AB - We examined Medicaid coverage patterns in five states for children who were covered as of December 2003. Looking back three years, we found that Medicaid was a source of continuous coverage for sizable proportions of children (43-66 percent were covered for two or more years) but a revolving door for others (16 41 percent had gaps). In all states, gaps were short, from two to four months. Continuity implies that states can demand more of the health care system to improve the quality of care; short gaps imply that policies and procedures should be revisited to reduce gaps for eligible children. PMID- 17339683 TI - Substitution of SCHIP for private coverage: results from a 2002 evaluation in ten states. AB - This paper examines the extent to which the State Children's Health Insurance Program (SCHIP) might be substituting for private health insurance coverage at the time of enrollment. Among children who were newly enrolled in SCHIP in 2002 in ten states, about 14 percent had private coverage that they could have retained as an alternative to SCHIP. Of this 14 percent, about half of parents reported that the private coverage was unaffordable compared with SCHIP. This suggests that relatively few SCHIP enrollees could have retained private coverage and that even fewer had parents who felt that the option was affordable. PMID- 17339684 TI - Can private companies contribute to public programs' outreach efforts? Evidence from California. AB - We studied an innovative outreach effort in California, which trains and certifies community organizations to help complete Medicaid and State Children's Health Insurance Program (SCHIP) applications. In this paper we provide a detailed description of participating organizations, the populations they serve, and their success at turning submitted applications into enrollments. We found that insurance brokers and income tax preparers-for-profit groups that are not typically associated with outreach-make important contributions to Medicaid and SCHIP in California. Brokers, in particular, help serve a hard-to-reach population: those on the higher end of the income eligibility thresholds. PMID- 17339685 TI - Family structure and children's physical and mental health. AB - Using the 2003 National Survey of Children's Health, this paper examines the physical and mental health of children by family structure. Children in step, single-mother, or grandparent-only families had poorer health than children living with two biological parents. Adjusting for demographic differences reduced observed disparities, although children living in single-mother or grandparent only families still had poorer health than children living with two biological parents. Adjusted estimates showed that children in single-father families generally did as well as (for mental health) or better than (for physical health) children living with two biological parents. PMID- 17339686 TI - Newborn screening: current status. AB - Newborn screening, which represents one of the major advances in child health of the past century, has been carried out in all fifty U.S. states since the 1970s. Newborn screening programs are state-run, and decisions are left to the individual states regarding the conditions to be screened for, the mechanism for confirmatory testing, follow-up care, and financing of the programs. Laboratory advances in tandem mass spectrometry make it possible to screen newborns for many rare inborn errors of metabolism. This raises many policy issues including screening's cost-effectiveness, ethics, quality, and oversight. PMID- 17339687 TI - Collaborating to combat childhood obesity. AB - Despite outstanding advances in children's health over the past several decades, rates of childhood obesity are near epidemic proportions. This paper highlights foundations' efforts to fight childhood obesity by convening organizations and effecting change at many levels of the community. PMID- 17339689 TI - Reductions in firearm-related mortality and hospitalizations in Brazil after gun control. AB - This paper provides evidence suggesting that gun control measures have been effective in reducing the toll of violence on population health in Brazil. In 2004, for the first time in more than a decade, firearm-related mortality declined 8 percent from the previous year. Firearm-related hospitalizations also reversed a historical trend that year by decreasing 4.6 percent from 2003 levels. These changes corresponded with anti-gun legislation passed in late 2003 and disarmament campaigns undertaken throughout the country since mid-2004. The estimated impact of these measures, if they prove causal, could be as much as 5,563 firearm-related deaths averted in 2004 alone. PMID- 17339690 TI - Health care in New Zealand. PMID- 17339692 TI - Today or tomorrow? PMID- 17339693 TI - Advocacy and policy change. PMID- 17339694 TI - Lessons for the insurance world. PMID- 17339695 TI - Advocacy has many paths. PMID- 17339699 TI - CsAl(H(2)AsO(4))(2)(HAsO(4)): a new monoclinic protonated arsenate with decorated krohnkite-like chains. AB - The crystal structure of hydrothermally synthesized caesium aluminium bis[dihydrogen arsenate(V)] hydrogen arsenate(V), CsAl(H(2)AsO(4))(2)(HAsO(4)), was determined from single-crystal X-ray diffraction data collected at room temperature. The compound represents a new structure type that is characterized by decorated krohnkite-like [100] chains of corner-sharing AlO(6) octahedra and AsO(4) tetrahedra. Ten-coordinated Cs atoms are situated between the chains, which are interconnected by five different hydrogen bonds [O...O = 2.569 (4) 2.978 (4) A]. All atoms are in general positions. CsAl(H(2)AsO(4))(2)(HAsO(4)) is very closely related to CsGa(H(1.5)AsO(4))(2)(H(2)AsO(4)) and isotypic CsCr(H(1.5)AsO(4))(2)(H(2)AsO(4)). PMID- 17339700 TI - Bis(1-phenylethylammonium) hexachloridostannate(IV) and bis(2 phenylethylammonium) hexachloridostannate(IV). AB - The crystal structures of the two isomers bis(1-phenylethylammonium) hexachloridostannate(IV) and bis(2-phenylethylammonium) hexachloridostannate(IV), both (C(8)H(12)N)(2)[SnCl(6)], exhibit alternating organic and inorganic layers, which interact via N-H...Cl hydrogen bonding. The inorganic layer contains an extended two-dimensional hydrogen-bonded sheet. The Sn atom in the 1 phenylethylammonium salt lies on an inversion centre. PMID- 17339701 TI - Aqua(phthalocyaninato)magnesium n-propylamine disolvate. AB - The crystals of the title compound, [Mg(C(32)H(16)N(8))(H(2)O)].2C(3)H(9)N, are built up from MgPc(H(2)O) [Pc is phthalocyaninate(2-)] and n-propylamine molecules that interact via O-H...N hydrogen bonds. The MgPc(H(2)O) molecule is non-planar. The central Mg atom is coordinated by the four equatorial isoindole N atoms of the Pc ring system and by the O atom of an axial water molecule. The Mg atom is displaced by 0.509 (1) A from the N(4) plane towards the water O atom. MgPc(H(2)O).2(n-propylamine) molecules related by the inversion centre are linked by N-H...O hydrogen bonds to form a dimeric aggregate. PMID- 17339702 TI - Aquabis(3-methoxy-2-pyridonato)(2,2':6',2''-terpyridine)ruthenium(II) acetonitrile-water (1/1/1). AB - The title compound, [Ru(C(6)H(6)NO(2))(2)(C(15)H(11)N(3))(H(2)O)] x CH(3)CNx H(2)O, is a transfer hydrogenation catalyst supported by nitrogen-donor ligands. This octahedral Ru(II) complex features rare monodentate coordination of 3 methoxy-2-pyridonate ligands and interligand S(6)S(6) hydrogen bonding. Comparison of the title complex with a structural analog with unsubstituted 2 pyridonate ligands reveals subtle differences in the orientation of the ligand planes. PMID- 17339703 TI - mu-{N,N'-Bis[2-(dimethylamino)ethyl]oxamidato(2-)} 1kappa(2)O,O':2kappa(4)N,N',N'',N'''-bis(4,4'-dimethyl-2,2'-bipyridine 1kappa(2)N,N')dinickel(II) bis(perchlorate). AB - In the crystal structure of the title complex, [Ni(2)(C(10)H(20)N(4)O(2))(C(12)H(12)N(2))(2)](ClO(4))(2) or [Ni(dmaeoxd)Ni(dmbp)(2)](ClO(4))(2) {H(2)dmaeoxd is N,N'-bis[2 (dimethylamino)ethyl]oxamide and dmbp is 4,4'-dimethyl-2,2'-bipyridine}, the deprotonated dmaeoxd(2-) ligand is in a cis conformation and bridges two Ni(II) atoms, one of which is located in a slightly distorted square-planar environment, while the other is in an irregular octahedral environment. The cation is located on a twofold symmetry axis running through both Ni atoms. The dmaeoxd(2-) ligands interact with each other via C-H...O hydrogen bonds and pi-pi interactions, which results in an extended chain along the c axis. PMID- 17339704 TI - catena-Poly[[tetrakis(mu-propionato-kappa(2)O:O')dicopper(II)]-mu-3 pyridylmethanol-kappa(2)N:O-[bis(propionato-kappaO)bis(3-pyridylmethanol kappaN)copper(II)]-mu-3-pyridylmethanol-kappaO:N]. AB - The title compound, [Cu(3)(C(3)H(5)O(2))(6)(C(6)H(7)NO)(4)](n), is composed of polymeric chains formed by alternating centrosymmetric Cu(2)(mu CH(3)CH(2)CO(2))(4) and Cu(C(3)H(5)O(2))(2)(C(6)H(7)NO)(2) units. These elemental units are linked by two bridging 3-pyridylmethanol (3PM) ligands. The Cu(2)(mu CH(3)CH(2)CO(2))(4) group presents a centrosymmetric tetrabridged structure with four syn-syn bridging propionate ligands to which two 3PM molecules are bonded (through N), occupying the apical positions of each square-pyramidal polyhedron around the Cu(II) ions. The remaining mononuclear group is centred around a third Cu(II) ion, which lies on a symmetry centre and is bound to two monodentate propionate groups (through O), two monodentate 3PM molecules (through N) and two bridging 3PM molecules (through O), thus completing a square-bipyramidal CuO(2)N(2)O(2) coordination. PMID- 17339705 TI - Tetraaquabis(5-carboxy-2-nitrobenzoato-kappaO)manganese(II) dihydrate: a metal water chain complex containing cyclic water tetramers. AB - In the title complex, [Mn(C(8)H(4)NO(6))(2)(H(2)O)(4)] x 2H(2)O, cyclic water tetramers forming one-dimensional metal-water chains have been observed. The water clusters are trapped by the co-operative association of coordination interactions and hydrogen bonds. The Mn(II) ion resides on a center of symmetry and is in an octahedral coordination environment comprising two O atoms from two 5-carboxy-2-nitrobenzoate ligands and four O atoms from water molecules. PMID- 17339706 TI - A novel dimeric zinc(II) complex: bis[mu-1,2-bis(1H-1,2,4-triazol-1-yl)ethane kappa(2)N(4):N(4')]bis[diisothiocyanatozinc(II)]. AB - The coordination geometry of the Zn(II) atom in the title complex, [Zn(2)(NCS)(4)(C(6)H(8)N(6))(2)], is that of a distorted tetrahedron, in which the Zn(II) atom is coordinated by four N atoms from the triazole rings of two symmetry-related 1,2-bis(1,2,4-triazol-1-yl)ethane ligands and two thiocyanate ligands. Two Zn(II) atoms are bridged by two organic ligands to form a dimer. The dimer lies about an inversion center. PMID- 17339707 TI - A polymeric zinc thiosulfate complex containing anionic and cationic chains based on tetrahedral and octahedral zinc sites. AB - catena-Poly[[[tetraaquazinc(II)]-mu-4,4'-bipyridine-kappa(2)N:N'] [[mu thiosulfato-kappa(2)O:S-bis[(thiosulfato-kappaS)zinc(II)]]-di-mu-4,4'-pyridine kappa(4)N:N'] dihydrate], {[Zn(C(10)H(8)N(2))(H(2)O)(4)][Zn(2)(S(2)O(3))(3)(C(10)H(8)N(2))(2)].2H(2)O}(n), is a polymeric zinc complex built up from thiosulfate-containing anionic chains, where the Zn atom is tetrahedrally coordinated, and aqua-containing cationic chains incorporating octahedrally coordinated Zn. In each type of chain, the 4,4' bipyridine units act as spacers, and the chains run along three non-intersecting almost orthogonal directions in space. The profusion of hydrogen-bond donors (all the H atoms of the water molecules) and acceptors (the thiosulfate O and S atoms) generates a very complex hydrogen-bonding scheme. PMID- 17339708 TI - 3-Methylamido-3',4'-ethylenedithiotetrathiafulvalene(+) potassium tetraisothiocyanatomercury(II). AB - In the title compound, (C(10)H(9)NOS(6))K[Hg(SCN)(4)] or (EDT-TTF CONHMe)K[Hg(SCN)(4))], fully oxidized organic (EDT-TTF-CONHMe)(+.) radical cations form quasi-one-dimensional stacks running along the monoclinic 2(1) axis and alternating along the crystallographic [101] direction with inorganic anion stacks made from mixed K(+)-[Hg(SCN)(4)](2-) ribbons. For each anion, three essentially collinear SCN ligands interact with the K(+) ions via short N...K contacts, while the terminal N atom of the fourth SCN group is engaged in a number of hydrogen-bond contacts with the -CH, -NH and -CH(2) hydrogen-bond donors of the amide function. Radical cations are dimerized along the stacks and the crystal conductivity is activated. PMID- 17339709 TI - alpha-Tris(2,4-pentanedionato-kappa(2)O,O')aluminum(III) at 240, 210, 180, 150 and 110 K: a new delta phase at 110 K. AB - The crystal structure of the title compound, [Al(C(5)H(7)O(2))(3)], has been investigated by a multi-temperature measurement to provide information on thermal vibrations and disorder in the structure. At 110 K, the structure of a new delta polymorph could be determined. A disorder-order phase transition takes place between 150 and 110 K and is klassengleich. The unit-cell volume increases by a factor of three and the diffraction pattern shows weak supercell reflections. PMID- 17339710 TI - Competing hydrogen-bond acceptors in ethylenediammonium oxotrithiotungstate(VI). AB - The structure of the title compound, (C(2)H(10)N(2))[WOS(3)], consists of ethylenediammonium dications and tetrahedral [WOS(3)](2-) dianions, which are linked with the aid of four varieties of hydrogen bond, namely N-H...O, N-H...S, C-H...O and C-H...S. The strength and number of these hydrogen bonds affect the W O and W-S bond distances. PMID- 17339711 TI - catena-Poly[[copper(II)-mu-2-[bis(2-pyridylmethyl)amino]butyrato kappa(4)N,N',N'',O:kappaO'] perchlorate]. AB - The copper(II) ion in the syn-anti carboxylate-bridged one-dimensional zigzag chain title complex, {[Cu(C(16)H(18)N(3)O(2))]ClO(4)}(n), exhibits a distorted trigonal-bipyramidal environment. Two N atoms and one carboxylate O atom of the ligand form the basal plane, while the axial positions are filled by an N atom of the ligand and one O atom belonging to the carboxylate group of an adjacent molecule. The crystal packing is enhanced by C-H...O(perchlorate) hydrogen bonds. PMID- 17339712 TI - catena-Poly[[(N,N-dimethylformamide-kappaO)(nitrato-kappaO)silver(I)]-mu-1,2 bis(diphenylphosphino)ethane-kappa(2)P:P'] at 100 and 293 K: temperature effects on the volume of the solvent pocket. AB - In the title chain compound, [Ag(NO(3))(C(3)H(7)NO)(C(26)H(24)P(2))](n), the bis(diphenylphosphino)ethane (dppe) components lie across centres of inversion. The dppe units link the Ag(+) ions into chains along [100]. A nitrate anion is coordinated to the Ag atom, together with one molecule of N,N-dimethylformamide (DMF) solvent. At room temperature, the coordinated DMF shows a long Ag-O distance [2.620 (3) A] and relatively large thermal motion, while at 100 K the Ag O distance is shorter [2.5588 (19) A] and the thermal motion is similar to that of the rest of the complex. The behaviour of the DMF molecule is related to the size of the solvent pocket, viz. 146 A(3) at 293 K and 131 A(3) at 100 K. PMID- 17339713 TI - catena-Poly[[aquabarium(II)]-mu-aqua-bis(mu-2'-carboxybiphenyl-2-carboxylato)]. AB - In the title compound, [Ba{HOOC(C(6)H(4))(2)CO(2)}(2)(H(2)O)(2)] or [Ba(C(14)H(9)O(4))(2)(H(2)O)(2)], the Ba atoms are coordinated by nine O atoms, six from two 2'-carboxybiphenyl-2-carboxylate (Hbpdc(-)) ligands and three from three coordinated water molecules, resulting in the formation of face-sharing distorted monocapped square antiprisms. The Hbpdc(-) ligands bridge the Ba atoms to form a one-dimensional helical polymer, with a Ba...Ba distance across the chain of 4.1386 (17) A. Adjacent chains are parallel to each other. The two independent ligands are tetradentate and have the same coordination mode, exhibiting mu-oxo bridges and eta(8)-chelation. The crystal structure is further stabilized by hydrogen bonds within each chain. PMID- 17339714 TI - Tetraaqua(1,10-phenanthroline-kappa(2)N,N')cobalt(II) dinitrate: a hydrogen bonded supramolecular network. AB - The structure of the title compound, [Co(C(12)H(8)N(2))(H(2)O)(4)](NO(3))(2), consists of tetraaqua(1,10-phenanthroline)cobalt(II) cations and nitrate anions. The Co atom is located on a twofold rotation axis and is coordinated by the two N atoms of a 1,10-phenanthroline ligand and four O atoms of water molecules. The cations and anions are linked by hydrogen-bond interactions into a three dimensional supramolecular network. PMID- 17339715 TI - Isostructural crystal packing and hydrogen bonding in alkylammonium tin(IV) chloride compounds. AB - The three isostructural compounds butylammonium hexachloridotin(IV), pentylammonium hexachloridotin(IV) and hexylammonium hexachloridotin(IV), (C(n)H(2n+1)NH(3))(2)[SnCl(6)], with n = 4, 5 and 6, respectively, crystallize as inorganic-organic hybrids. As such, the structures consist of layers of [SnCl(6)](2-) octahedra, separated by hydrocarbon layers of interdigitated butylammonium, pentylammonium or hexylammonium cations. Corrugated layers of cations alternate with tin(IV) chloride layers. The asymmetric unit in each compound consists of an anionic component comprising one Sn and two Cl atoms on a mirror plane, and two Cl atoms in general positions; the two cations lie on another mirror plane. Application of the mirror symmetry generates octahedral coordination around the Sn atom. All compounds exhibit bifurcated and simple hydrogen-bonding interactions between the ammonium groups and the Cl atoms, with little variation in the hydrogen-bonding geometries. PMID- 17339716 TI - 2,3-Difluoro-4-formylphenylboronic acid. AB - The molecule of the title compound, 2,3-F(2)-4-(CHO)C(6)H(2)B(OH)(2) or C(7)H(5)BF(2)O(3), contains a formyl group coplanar with the benzene ring. The boronic acid group is twisted with respect to the benzene ring plane. The molecules are organized into infinite chains via intermolecular O-H...O hydrogen bonds. These chains are additionally connected via strong O-H...O hydrogen bonds, producing a folded layer structure perpendicular to the a axis. These layers are paired due to B...F interactions. PMID- 17339717 TI - N-Benzyltetrahydropyrido-anellated thiophene derivatives: new anticholinesterases. AB - The title compounds, tert-butyl 6-benzyl-2-(3,3-diethylureido)-4,5,6,7 tetrahydrothieno[2,3-c]pyridine-3-carboxylate, C(24)H(33)N(3)O(3)S, (I), 7-benzyl 2-diethylamino-5,6,7,8-tetrahydro-3-oxa-9-thia-1,7-diazafluoren-4-one, C(20)H(23)N(3)O(2)S, (II), and N-(7-benzyl-4-oxo-5,6,7,8-tetrahydro-4H-3,9-dithia 1,7-diazafluoren-2-yl)benzamide, C(23)H(19)N(3)O(2)S(2), (III), form monoclinic crystal systems. In (I) and (II), the molecules are linked into a three dimensional framework by weak intermolecular C-H...O=C hydrogen bonds, whereas in (III) stronger intermolecular N-H...O=C interactions are observed. The conformation of (I) is further stabilized by an intramolecular N-H...O=C hydrogen bond, which effects the planarity of the ureidothiophenecarboxylate moiety. PMID- 17339718 TI - Dimorphism in 4,4,6,6-tetrachloro-2,2-(2,2-dimethylpropane-1,3 dioxy)cyclotriphosphazene and 6,6-dichloro-2,2:4,4-bis(2,2-dimethylpropane-1,3 dioxy)cyclotriphosphazene. AB - A second, polymorphic, form of the previously reported compound 4,4,6,6 tetrachloro-2,2-(2,2-dimethylpropane-1,3-dioxy)cyclotriphosphazene, C(5)H(10)Cl(4)N(3)O(2)P(3), is now reported. The molecular structures of these two compounds are similar, aside from minor conformational differences. However, the compounds crystallize in two different space groups and exhibit quite different crystal structure assemblies. Additionally, 6,6-dichloro-2,2:4,4 bis(2,2-dimethylpropane-1,3-dioxy)cyclotriphosphazene, C(10)H(20)Cl(2)N(3)O(4)P(3), is shown to exhibit two different conformational polymorphs when crystallized from different solvent mixtures. The alpha form crystallizes in the space group Pnma with the molecular structure lying on a mirror plane (symmetry code: x, -y + {1/2}, z), whilst the beta form is in the space group C2/c with the molecular structure lying on a twofold axis (symmetry code: -x, y, -z + {3/2}). The difference between the two molecular structures is in the conformation of the spiro-ring substituents with respect to the phosphazene ring. The resulting crystal structures give rise to differing packing motifs. PMID- 17339719 TI - 1-Benzyl-3,3-dichloro-1H-indol-2(3H)-one. AB - The title compound, C(15)H(11)Cl(2)NO, was synthesized from N-benzyl isatin. The compound crystallizes as stacks of molecules running down the c axis. Molecules within each of these stacks interact with each other through pi-pi and C-H...pi interactions, and interact with neighbouring stacks through C-H...O interactions. PMID- 17339720 TI - 6-(4-Fluorophenyl)-8-phenyl-2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one: an unusual [6-5] fused-ring system. AB - The title compound, C(18)H(13)FN(2)OS, is the first structural example of a [6-5] fused ring incorporating the 2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one molecular scaffold. The six-membered 2,3-dihydro-1,3-thiazin-4-one ring adopts an envelope conformation, with the S-CH(2) C atom displaced by 0.761 (2) A from the five-atom plane (all within 0.05 A of the mean plane). The imidazole ring is planar. The phenyl ring is twisted from coplanarity with the imidazole ring by 23.84 (5) degrees and the 4-fluorophenyl ring is twisted by 53.36 (6) degrees , due to a close C(aryl)-H...O=C contact with the thiazin-4-one carbonyl O atom. The primary intermolecular interaction involves a CH(2) group with the F atom [C...F = 3.256 (2) A and C-H...F = 137 degrees ]. PMID- 17339721 TI - Stereoisomers of 1,2-diaryl-1,3-propanediols: erythro forms. AB - Racemic erythro-1,2-diphenyl-1,3-propanediol, C(15)H(16)O(2), is a model compound representative of erythro forms of structural elements of the 1,2-diaryl-1,3 propanediol type in lignins. In the crystal structure, the torsion angle between the bulky phenyl groups is -62.26 (11)degrees. Strong hydrogen bonds take part in a directed co-operative O-H...O-H...O-H...O-H pattern that is assumed to have a decisive influence on the conformation. This is supported by comparisons with the geometries of related compounds. PMID- 17339722 TI - 4-Cyanobenzaldehyde isonicotinoylhydrazone monohydrate: a three-dimensional hydrogen-bonded framework structure. AB - In the title compound, C(14)H(10)N(4)O.H(2)O, the molecular components are linked into a three-dimensional framework by three hydrogen bonds, one each of the O H...O, O-H...N and N-H...O types, weakly augmented by two C-H...O hydrogen bonds. PMID- 17339723 TI - Cocrystallization and configurations of myo-inositol-1,2-L-camphor acetals in two crystal structures. AB - The inositol rings in (1S,2R,3R,4S,5S,6R,7S,8S,11S)-myo-inositol-1,2-camphor acetal {systematic name: (1R,2S,3S,4R,5S,6R)-5,6-[(1S,2S,4S)-1,7,7 trimethylbicyclo[2.2.1]heptane-2,2-diyldioxy]cyclohexane-1,2,3,4-tetrol}, C(16)H(26)O(6), and (1R,2S,3S,4R,5R,6S,7R/S,8S,11S)-myo-inositol-1,2-camphor acetal trihydrate {systematic name: (1S,2R,3R,4S,5R,6S)-5,6-[(1S,4S,6R/S)-1,7,7 trimethylbicyclo[2.2.1]heptane-2,2-diyldioxy]cyclohexane-1,2,3,4-tetrol trihydrate}, C(16)H(26)O(6).3H(2)O, adopt flattened chair conformations with the latter crystal containing two stereoisomers in a 0.684 (2):0.316 (2) ratio, similar to that found both in solution and by calculation. Both molecules pack in the crystals in similar two-dimensional layers, utilizing strong O-H...O hydrogen bonds, with the trihydrate cell expanded to incorporate the additional hydrogen bonded water molecules. PMID- 17339724 TI - 6-Aza-2'-deoxyuridine and N(3)-anisoyl-6-aza-2'-deoxyuridine. AB - In 2-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,4-triazine-3,5(2H,4H)-dione (6 aza-2'-deoxyuridine), C(8)H(11)N(3)O(5), (I), the conformation of the glycosylic bond is between anti and high-anti [chi = -94.0 (3) degrees ], whereas the derivative 2-(2-deoxy-beta-D-erythro-pentofuranosyl)-N(4)-(2-methoxybenzoyl) 1,2,4-triazine-3,5(2H,4H)-dione (N(3)-anisoyl-6-aza-2'-deoxyuridine), C(16)H(17)N(3)O(7), (II), displays a high-anti conformation [chi = -86.4 (3) degrees]. The furanosyl moiety in (I) adopts the S-type sugar pucker ((2)T(3)), with P = 188.1 (2) degrees and tau(m) = 40.3 (2) degrees, while the sugar pucker in (II) is N ((3)T(4)), with P = 36.1 (3) degrees and tau(m) = 33.5 (2) degrees. The crystal structures of (I) and (II) are stabilized by intermolecular N-H...O and O-H...O interactions. PMID- 17339725 TI - Three (E)-2-[(bromophenyl)iminomethyl]-4-methoxyphenols. AB - The title compounds, (E)-2-[(2-bromophenyl)iminomethyl]-4-methoxyphenol, C(14)H(12)BrNO(2), (I), (E)-2-[(3-bromophenyl)iminomethyl]-4-methoxyphenol, C(14)H(12)BrNO(2), (II), and (E)-2-[(4-bromophenyl)iminomethyl]-4-methoxyphenol, C(14)H(12)BrNO(2), (III), adopt the phenol-imine tautomeric form. In all three structures, there are strong intramolecular O-H...N hydrogen bonds. Compound (I) has strong intermolecular hydrogen bonds, while compound (III) has weak intermolecular hydrogen bonds. In addition to these intermolecular interactions, C-H...pi interactions in (I) and (III), and pi-pi interactions in (I), play roles in the crystal packing. The dihedral angles between the aromatic rings are 15.34 (12), 6.1 (3) and 39.2 (14) degrees for (I), (II) and (III), respectively. PMID- 17339726 TI - The 1:1 cocrystals of the proton-transfer compound dilituric acid- phenylbiguanide monohydrate. AB - A proton-transfer compound, 1-phenylbiguanidium 5-nitro-2,6-dioxo-1,2,3,6 tetrahydropyrimidin-4-olate monohydrate, C(8)H(12)N(5)(+) x C(4)H(2)N(3)O(5)(-) x H(2)O, has been synthesized by a reaction between dilituric acid (5-nitro-2,4,6 trihydroxypyrimidine, Dilit) and phenylbiguanide (N-phenylimidocarbonimidic diamide, Big). This compound cocrystallized as a 1:1 adduct, and the asymmetric unit consists of two dilituric amino-oxo planar tautomeric anions (Dilit(-)), two monoprotonated phenylbiguanidium cations (BigH(+)) and two water molecules of crystallization (Z' = 2). Protonation occurs at the N atom attached to the phenyl ring of Big as a result of the proton-transfer process from the acidic hydroxy group of Dilit. In the crystal structure, the hydrated 1:1 adduct is stabilized by 25 two- and three-center hydrogen bonds. PMID- 17339727 TI - 4,5-Dibromophthalimide forms two centrosymmetric dimers, one linked by C-H...O hydrogen bonds and one by N-H...O hydrogen bonds. AB - In the title compound [also called 5,6-dibromoisoindole-1,3(2H)-dione], C(8)H(3)Br(2)NO(2), there are two planar molecules in the asymmetric unit. They both form inversion dimers, one via N-H...O links and one via short near-linear C H...O links. The dimers are then linked into chains by further N-H...O hydrogen bonds. PMID- 17339728 TI - 2-(2-Oxazolin-2-yl)benzene-1,4-diol: X-ray and density functional theory studies. AB - In the crystal structure of the title compound, C(9)H(9)NO(3), there are strong intramolecular O-H...N and intermolecular O-H...O hydrogen bonds which, together with weak intermolecular C-H...O hydrogen bonds, lead to the formation of infinite chains of molecules. The calculated intermolecular hydrogen-bond energies are -11.3 and -2.7 kJ mol(-1), respectively, showing the dominant role of the O-H...O hydrogen bonding. A natural bond orbital analysis revealed the electron contribution of the lone pairs of the oxazoline N and O atoms, and of the two hydroxy O atoms, to the order of the relevant bonds. PMID- 17339729 TI - 1,17-Diphenyl-2,4,6,8,10,12,14,16-octaoxaheptadecane. AB - The title compound, C(21)H(28)O(8), crystallizes with two independent molecules, each with a crystallographic twofold axis passing through the central CH(2) group. The two molecules have different orientations of the terminal benzyl groups. The average C-O bond length in the polyoxymethylene helix, corrected for librational motion, is 1.419 A. The molecules are connected into layers by intermolecular C-H...O and C-H...pi(phenyl) interactions. PMID- 17339730 TI - A second polymorph of bis(dimethylphosphino)dimethylphosphonium trifluoromethanesulfonate. AB - The title compound, C(6)H(18)P(3)(+) x CF(3)SO(3)(-), crystallizes in two polymorphic forms in the space groups P2(1)/c and Pnma. In the orthorhombic form, the two crystallographically independent molecular units lie across a crystallographic mirror plane. The compound lacks traditional hydrogen-bond donors and, hence, is held together by weak C-H...O and C-H...F interactions, forming layers. The second polymorph was obtained as a by-product from the reaction of 1,3-bis(2,6-dimethylphenyl)-2,4-ditriflato-1,3,2,4 diazadiphosphetidine with tetramethyldiphosphine. PMID- 17339731 TI - Four (E,Z,E)-1-(4-alkoxyphenyl)-6-(4-nitrophenyl)hexa-1,3,5-trienes. AB - The crystal structures of the four E,Z,E isomers of 1-(4-alkoxyphenyl)-6-(4 nitrophenyl)hexa-1,3,5-triene, namely (E,Z,E)-1-(4-methoxyphenyl)-6-(4 nitrophenyl)hexa-1,3,5-triene, C(19)H(17)NO(3), (E,Z,E)-1-(4-ethoxyphenyl)-6-(4 nitrophenyl)hexa-1,3,5-triene, C(20)H(19)NO(3), (E,Z,E)-1-(4-nitrophenyl)-6-(4-n propoxyphenyl)hexa-1,3,5-triene, C(21)H(21)NO(3), and (E,Z,E)-1-(4-n butoxyphenyl)-6-(4-nitrophenyl)hexa-1,3,5-triene, C(22)H(23)NO(3), have been determined. Intermolecular N...O dipole interactions between the nitro groups are observed for the methoxy derivative, while for the ethoxy derivative, two adjacent molecules are linked at both ends through N...O dipole-dipole interactions between the N atom of the nitro group and the O atom of the ethoxy group to form a supramolecular ring-like structure. In the crystal structures of the n-propoxy and n-butoxy derivatives, the shortest intermolecular distances are those between the two O atoms of the alkoxy groups. Thus, the nearest two molecules form an S-shaped supramolecular dimer in these crystal structures. PMID- 17339732 TI - Supramolecular motifs in 1-(2-cyanoethyl)thymine and 1-(3-cyanopropyl)thymine. AB - In both 1-(2-cyanoethyl)thymine [systematic name: 3-(5-methyl-2,4-dioxo-1,2,3,4 tetrahydropyrimidin-1-yl)propanenitrile], C(8)H(9)N(3)O(2), (I), and 1-(3 cyanopropyl)thymine [systematic name: 4-(5-methyl-2,4-dioxo-1,2,3,4 tetrahydropyrimidin-1-yl)butanenitrile], C(9)H(11)N(3)O(2), (II), the core of the supramolecular structure is formed by centrosymmetric dimers generated by N-H...O hydrogen bonds. Further weak hydrogen bonds of C-H...O and C-H...N types generate molecular tapes and sheets that resemble those in uracil and its methyl derivatives. The steric hindrance that arises from the cyanoalkyl substituents perturbs the conformations of the tapes and sheets. PMID- 17339733 TI - (3S)-Benzyl N-(1-hydroxy-2,5-dioxopyrrolidin-3-yl)carbamate: two-dimensional sheets built from O-H...O, N-H...O, C=O...C=O and C-H...O interactions linked into a three-dimensional complex framework via C-H...pi(arene) interactions. AB - The title compound, C(10)H(12)O(5)N(2), crystallizes with two independent molecules in the asymmetric unit. The molecules in the crystal structure are arranged into one-dimensional substructural ribbon motifs stabilized by a combination of two O-H...O and three N-H...O intermolecular hydrogen bonds, and also augmented by short C=O...C=O carbonyl-carbonyl interactions. Two intermolecular C-H...O short contacts between adjacent ribbons generate complex two-dimensional sheets on the ab plane. Adjacent sheets are linked via C H...pi(arene) interactions, resulting in a complex three-dimensional framework. PMID- 17339734 TI - [Mechanism of vascular calcification]. AB - Vascular calcification is clinically important in the development of cardiovascular disease. It has been suggested that apoptosis and chondro/osteogenic differentiation of vascular smooth muscle cells (VSMC) play important roles in the initiation and progression of vascular calcification. During the process of vascular calcification, growth arrest-specific gene 6 (Gas6) mediated-survival pathway is downregulated in VSMC, leading to apoptosis. Chondro/osteogenic differentiation regulated by transcription factors such as core binding factor alpha1 (Cbfa1) or msh homeo box homolog 2 (Msx2), promotes VSMC calcification. It is clear that vascular calcification is an active process regulated by various factors including Gas6, Cbfa1, or Msx2. PMID- 17339735 TI - [Clinical implication of coronary calcification]. AB - Calcification is a common finding in human coronary arteries, which is generally associated with long-standing atherosclerosis. However, there is conflicting evidence for the link between calcification and plaque instability. Recent histopathological studies have revealed that plaque calcification is present in 69% of ruptured plaques in sudden coronary death. Furthermore, studies using electron-beam computed tomography have reported that calcium score relates to acute coronary events. Recently, we clarified that in patients with acute myocardial infarction small "spotty" calcifications prevailed, associated with a fibrofatty plaque and positive remodeling. Future studies would focus on the clinical implication of coronary calcification. PMID- 17339736 TI - [Pathology of coronary arterial calcification]. AB - Calcification is an invariable component of advanced coronary artery atherosclerosis. Recent study showed that genetic variations such as matrix inhibitory proteins, polymorphisms for tumor necrosis factor, and inflammatory cytokines may influence coronary artery calcification. And also there have been numerous studies on screening patients for coronary artery disease using electron beam computed tomography, but details of mechanism on calcification have still been unclear. An example of coronary calcification in diabetic patients disclosed that its diffuse distribution might be metabolic on calcification mechanism. PMID- 17339737 TI - [Calcified coronary artery disease and serum markers]. AB - Severity of coronary artery calcification is closely related to atherosclerotic plaque burden and cardiac event rate. Recent data have suggested that vascular calcification is an actively regulated process similar to the bone formation, and that bone-related factors may be involved in the development of vascular calcification. Non-invasive prediction of calcified coronary artery disease is important using serum bone-related markers. Among them, we focus on matrix Gla protein, osteoprotegerin and fetuin-A as such candidates in this review. PMID- 17339738 TI - [Osteoporosis and atherosclerosis]. AB - Many epidemiological studies have shown an association between osteoporosis and vascular calcification or atherosclerotic diseases (coronary heart disease, stroke, peripheral vascular disease) in the elderly or postmenopausal women. These results indicate that osteoporosis and atherosclerosis might be linked by common risk factors or pathological mechanisms. Dyslipidemia has the correlation to both osteoporosis and atherosclerosis. Statins, nitorogen-containing bisphosphonates, and estrogens have the favorable effects on lipid profiles as well as vasculature, or bone mineral density. Thus, these therapeutic approaches might have dual effects on bone and vasculature. PMID- 17339739 TI - [Arteriosclerosis and vascular calcification in chronic kidney disease (CKD) patients]. AB - Chronic kidney disease (CKD) patients are belonging to high risk patients to atherosclerosis with vascular calcification. These patients are well recognized advanced arteriosclerosis with vascular medial calcification, with high risk of cardiovascular death. With basic investigated results, the mechanism of vascular calcification is making clear. A lot of various factors which participate in calcification have been specified. Especially, in long term dialysis patients, the very high grade vascular calcification with advanced atherosclerosis is common with calcium/phosphate/PTH and skeletal problem. This CKD related metabolic bone disorder (CKD-MBD) highly induced and progressed vascular calcification. Participates in vascular calcification. It is extremely important in order to prevent vascular calcification to manage serum phosphorus, serum calcium and parathyroid function within the suitable range. In addition, hyperphosphatemia is becoming the powerful risk factor for patients' survival. The new powerful phosphate binder is developing. The beneficial effect of the new agent on patients' survival is now focused. PMID- 17339740 TI - [Role of anti-angiogenic factor chondromodulin-I for maintaining cardiac valvular function]. AB - Cardiac valves are recognized as avascular tissue as well as cartilage and eye. We recently identified chondromodulin-I as crucial anti-angiogenic factor for maintaining cardiac valvular function. chondromodulin-I was first detected at developmental stage E9.5 in outflow tract, valvular primordium, and left ventricle, but was restricted to cardiac valves from late embryogenesis to adult. In ApoE(-/-) mice and human valvular heart diseases such as atherosclerosis, rheumatic heart diseases, and infective endocarditis, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) expression and neovascularization were observed in the area of down-regulation of chondromodulin I. Conditioned medium from cultured-valvular interstitial cells strongly inhibited tube formation and migration of endothelial cells, and these effects were partially blocked by chondromodulin-I siRNA in vitro. Gene targeting of chondromodulin-I caused VEGF expression, neovascularization, lipid deposition, and calcification in cardiac valves of aged mice. Echocardiography showed aortic valve thickening and turbulent flow suggesting early stage of aortic stenosis. These findings provide evidence that chondromodulin-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis that may lead to valvular heart diseases. PMID- 17339741 TI - [Carminerin contributes to chondrocyte calcification during pathological endochondral ossification]. AB - Endochondral ossification is an essential process not only for physiological skeletal development and growth, but also for pathological disorders such as osteophyte formation in osteoarthritic joints and ectopic ossification with ageing. We recently identified a novel cartilage-specific molecule carminerin. Although the carminerin-deficient mice developed and grew normally, pathological endochondral ossification were suppressed. We conclude that carminerin contributes to chondrocyte calcification during pathological endochondral ossification without affecting physiological skeletal conditions, suggesting that this molecule could be a therapeutic target for these disorders. PMID- 17339742 TI - [Treatment for coronary artery calcification]. AB - Coronary calcification frequently coexists with coronary atherosclerosis. Diagnosis methods are traditional coronary angiography, intravascular ultrasound, electron beam CT and muti-slice CT. Treatment for patients with calcified coronary arteries is troublesome. Rotablator or laser atherectomy are candidates for the treatment in coronary intervention. In bypass surgery, calcified area should be avoided for anastomosis. Treatment for coronary calcification itself is not standardized at present. PMID- 17339743 TI - [Bisphosphonates for vascular calcification]. AB - Recent progress in basic research has revealed certain similarities between processes of bone calcification and calcifications of vascular tissues which contribute to several cardiovascular diseases. Bisphosphonates, which are inhibitors of bone resorption that are widely used to treat osteoporosis, also inhibit cholesterol biosynthesis, differentiation of macrophage to foam cell, differentiation of smooth muscle cells to osteoblast-like cells in certain stimuli during calcification processes of vessels. These findings extend the link between bone remodeling and vascular calcification, opening perspectives toward novel therapeutic strategies, however, current evidence is not conclusive and further research is necessary to confirm these actions in the clinical setting. PMID- 17339744 TI - [Relationship between sevelamer HCl and vascular calcification]. AB - The Kidney Disease Outcomes Quality Initiative (K/DOQI) issued "Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease", in which it is recommended that the level of intact parathyroid hormone (i-PTH) should be kept at 150 - 300 pg/mL, the serum phosphorus (P) level at 3.5 - 5.5 mg/dL, and the serum calcium (Ca) level within the normal range of laboratory values (8.4 - 9.5 mg/mL, as close to the lower limit as possible). In developing these guidelines, the K/DOQI apparently considered the recently established fact that control of Ca, P and PTH influences not only the development of bone lesions but also patient prognostic factors such as arteriosclerosis, ectopic calcification, and cardiovascular complications, as well as the development of various vitamin D products and analogues and new P adsorbents. The Japanese guidelines also emphasize the control of P and Ca, rather than PTH. Therefore Phosphorus control is a primary goal in the care of patients with end-stage renal disease. We inspect the relationship between Vascular calcification and Sevelamer HCl, a non aluminium, non-calcium, non-absorbed phosphate binder. PMID- 17339745 TI - [Secondary osteoporosis. Glucocorticoid-induced osteoporosis: Threshold of bone mineral density for vertebral fracture]. AB - The use of systemic corticosteroids is one of independent risk factors with bone mineral density (BMD) for fractures. The prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the decrease of BMD. Cut-off value of lumbar BMD for vertebral fractures was 80% of young adult mean in Japanese patients. For management of glucocorticoid-induced osteoporosis, we have to concern about all risk factors of fracture including BMD and use the evidence-based guideline. PMID- 17339746 TI - Ukraine urinary iodine levels; 20 years after the Chernobyl accident. PMID- 17339747 TI - Deterioration of glycemic control during octreotide LAR treatment in an acromegalic Japanese patient with type 2 diabetes mellitus. AB - We report a case showing deterioration of glycemic control during octreotide long acting release (LAR) treatment in an acromegalic Japanese patient with type 2 diabetes mellitus. The patient did not show much improvement of insulin sensitivity (QUICKI; 0.33 before treatment, 0.35 during octreotide LAR treatment), and showed a significant reduction in early insulin secretion (insulinogenic index; 0.28 before treatment, 0.08 during octreotide LAR treatment) on 75 g oral glucose tolerance test (75gOGTT), despite decreases in GH and IGF-I levels during the course of octreotide LAR treatment. Postoperatively, both insulin sensitivity and early insulin secretion on 75gOGTT were improved (QUICKI 0.59, insulinogenic index 0.35). There are some reports that insulinogenic index is lower in most Japanese patients with type 2 diabetes mellitus and that early insulin secretions are significantly suppressed after administration of octreotide LAR. Although the influence of octreotide LAR on glucose metabolism varies among individuals, it is necessary to manage the deterioration of glucose tolerance during octreotide LAR treatment in acromegalic Japanese patients with decreased insulinogenic index. PMID- 17339748 TI - Administration of recombinant human growth hormone normalizes GH-IGF1 axis and improves malnutrition-related disorders in patients with anorexia nervosa. AB - High serum level of GH in the presence of low plasma level of insulin-like growth factor-I (IGF-I) is one of the endocrinological features of anorexia nervosa (AN). Whether the amount of endogenous GH is not enough to increase IGF-I is not certain. We studied the effect of recombinant human growth hormone (rhGH) on the GH-IGF-I axis and on malnutrition-related disorders in this syndrome. Twenty patients with AN were divided into two groups; one (N = 13) was given rhGH (0.33 mg/day), and the other (N = 7) was given placebo for 6 or 12 months, respectively. During each treatment, levels of serum GH, plasma IGF-I, serum thyroid hormones, serum cholesterol, fasting plasma glucose and cardiac function were monitored. Changes in body mass index (BMI) and calorie taken were also evaluated. Plasma IGF-I level increased from 74.4 +/- 41.9 to 269.0 +/- 31.2 microg/L (P<0.001) during administration of rhGH, which associated with a decrease in serum GH level from 17.0 +/- 15.0 to 1.6 +/- 0.8 microg/L (P<0.001). Administration of rhGH increased BMI, body temperature, fasting plasma glucose level, and food intake. Serum level of triiodothyronine, but not thyroxine, increased during treatment with rhGH. The treatment decreased serum levels of both total and HDL-cholesterol. Studies with echocardiography showed an increase in cardiac output during the treatment with rhGH. These improvements were not observed in patients treated with placebo. Administration of rhGH is recommended as one of the methods of managing the patients with AN. PMID- 17339749 TI - Responses of embryonic germ cells of the radiation-sensitive Medaka mutant to gamma-irradiation. AB - The radiation-sensitive mutant "ric1" has a defect in the repair mechanism of DNA double strand breaks induced by gamma-rays in early embryogenesis. In this study, the new radiation-sensitive Medaka (Oryzias latipes) strain, ric1olvas-GFP was established to monitor the development of germ cells in vivo. The development of germ cells was normal in ric1olvas-GFP, but embryonic germ cells at Stage 7 (32 cell stage) and Stage 33 (extensive proliferating stage of PGCs) showed higher radiosensitivity. There was no sex difference in germ cell radiosensitivity at Stage 7, but female embryos showed higher radiosensitivity than male at Stage 33. In embryos obtained by crossing ric1 female with olvas-GFP male, germ cells showed similar radiosensitivity to ric1olvas-GFP and increased sensitivity compared to embryos obtained from crossing wild-type female with olvas-GFP male at Stage 7. These results suggest that germ cells have the ric1 dependent DNA repair system during embryogenesis and the maternal ric1gene factor may play a critical role in radiosensitivity at an early developmental stage. PMID- 17339750 TI - Whole body exposure to low-dose gamma radiation promotes kidney antioxidant status in Balb/c mice. AB - We examined the effect of whole body low-dose gamma-irradiation on the status of the antioxidant defense system in the rodent kidneys at different time intervals. Young male Balb/c mice were exposed to whole body radiation from a (60)Co source at doses of 10, 25 and 50 cGy (48.78 cGy/min). Antioxidant status and lipid peroxidation were estimated in the kidneys at 4, 12 and 24 h after irradiation. Lipid peroxidation increased between 33% and 49% and reduced glutathione between 12% and 47% at 12 h at different radiation doses. Reduced glutathione level remained significantly (p < 0.05) elevated even at 24 h after irradiation to 25 cGy. Superoxide dismutase activity also increased by 37% at 12 h on exposure of animals to all the doses up to 50 cGy. Catalase activity increased significantly at 12 h on exposure to 10 cGy and 50 cGy. Interestingly, glutathione peroxidase activity increased by 31% at 4 h and subsequently returned to control levels at 24 h after exposure to 50 cGy. Glutathione reductase activity increased by 10-12% at 12 h after exposure to 25 cGy and 50 cGy. The results suggest that the whole body exposure of animals to gamma radiation stimulates the antioxidant defense system in the kidneys within 4 to 24 h after irradiation, at doses of 25 cGy and 50 cGy. PMID- 17339751 TI - Spontaneous differentiation of adult rat marrow stromal cells in a long-term culture. AB - It is well recognized that bone marrow stromal cells (MSCs) can differentiate into neuron-like cells when supplemented with growth factors and/or chemical treatments. We demonstrated that primary MSCs obtained from adult rats could spontaneously differentiate into neural precursor cells after long-term culture. During the outset of in vitro culture, less than 0.1% of adult rat primary MSCs expressed nestin, the common protein of neural precursors. These MSCs didn't show neuronal morphology nor express neuronal antigens. In contrast, after continuous maintenance for 6 weeks, a significant subpopulation of MSCs formed cellular clumps and expressed nestin (32.3 +/- 6.3%). Less than 0.1% of cells expressing immature neuron marker betaIII-tubulin could be detected in these prolonged cultured MSCs. After serum deprivation and growth factor supplement, these nestin positive cells could express neuron-like morphology and neuron-specific markers NF-H, betaIII-tubulin, tau, and neurotransmitter GABA. In contrast, the MSCs without prolonged culture didn't show neuronal morphology nor neuronal markers even after serum withdrawal and growth factors stimulation. These results demonstrated that neural precursors could be obtained from long-term cultured MSCs, and suggested that MSCs should be useful as a potential source for treatment of neurological disease. PMID- 17339752 TI - Evaluation of the low dose level of a heat-killed and dried cell preparation of Enterococcus faecalis to prevent porcine edema disease using experimental infection model with enterotoxcemic Escherichia coli in weaning pigs. AB - Porcine edema disease (ED) is caused by Shiga toxin 2e-producing Escherichia coli (STEC). ED has become frequent in pig farms, and the use of antimicrobials has resulted in the development of antimicrobial-resistant STEC. Accordingly, the use of materials other than antimicrobials is requested for the prevention of ED. Oral administration of a heat-killed and dried cell preparation of Enterococcus faecalis strain EC-12 (EC-12) to weaning pigs was previously demonstrated to decrease animal mortality in a STEC-contaminated farm at 0.05% (w/w) dose level. In this study, pigs experimentally infected with STEC were used as a model for ED to evaluate the low dose level of EC-12 to prevent ED. Fifteen 21-day-old pigs were divided into 5 groups: STEC challenge with the basal diet, STEC challenge with EC-12 supplemented at 0.005, 0.01, or 0.05% (w/w) to the basal diet, and no STEC challenge with the basal diet. The challenge was carried out when the animals were 25, 26, and 27 days old using STEC contained in capsules resistant against gastric digestion. All pigs were euthanized at 32 days of age. The daily weight gain, feed conversion ratio, and palpebral edema were improved by supplementation with 0.05% EC-12, but not by the low dose levels. Accordingly, 0.05% level of supplementation was needed for EC-12 to improve clinical symptoms in weaning piglets infected by STEC. PMID- 17339753 TI - Expression of the MDR1 gene and P-glycoprotein in canine mast cell tumor cell lines. AB - Cellular drug resistance to antineoplastic drugs is often due to the presence of a drug efflux pump that reduces intracellular drug accumulation and chemosensitivity. P-glycoprotein (P-gp), which is encoded by the MDR1 gene, is considered to function as an ATP-driven membrane drug efflux pump and appears to play an important role in tumor cell resistance. In the present report, we assessed the expression of MDR1 by RT-PCR in three canine mast cell tumor cell lines, TiMC, CoMS and LuMC, originating from a cutaneous tumor, an oral-mucosal tumor and a gastrointestinal tumor, respectively. P-gp expression was also examined by Western blot analysis, while the functional activity of P-gp was assessed by flowcytometric analysis of intracellular rhodamine-123 (Rhd-123) uptake. The results revealed that MDR1 gene and P-gp were both expressed in CoMS and LuMC cells, whereas neither was present in TiMC cells. In CoMS and LuMC cells, intracellular uptake of Rhd-123 increased in the presence of verapamil, a functional modulator of P-gp. In contrast, TiMC cells did not show any changes in the intracellular accumulation of Rhd-123 after the verapamil addition. These findings suggest that the expressions of MDR1 gene and P-gp probably contribute to cellular drug resistance in canine mast cell tumors. PMID- 17339754 TI - Evaluation of left ventricular Tei index (index of myocardial performance) in healthy dogs and dogs with mitral regurgitation. AB - The left ventricular (LV) Tei index (index of myocardial performance) has been demonstrated to be clinically useful in estimating comprehensive LV function, including the systolic and diastolic performances, in various human cardiac diseases. The purposes of this study were to validate the correlation between the LV Tei index and LV function obtained by cardiac catheterization in healthy dogs, and to evaluate the LV Tei index in dogs with naturally occurring mitral regurgitation (MR). In healthy dogs, the LV Tei index was significantly correlated with the LV peak +dP/dt (r = -0.89) and LV peak -dP/dt (r=0.87). The LV Tei index significantly increased in dogs with MR compared with normal dogs and significantly increased with progressively more severe clinical signs due to heart failure. The elevation of the LV Tei index in dogs with symptomatic MR appears to be associated with shortening of ejection time. The LV Tei index significantly increased with age and was not correlated with heart rate and body weight in normal dogs. In conclusion, our study demonstrated that the LV Tei index was measurable in dogs and not influenced by heart rate and body weight. The LV Tei index significantly increased with the progression of clinical signs in MR dogs. In particular, the elevation of the LV Tei index in dogs with symptomatic MR due to shortening of ejection time may suggest LV systolic dysfunction and the decrement of forward stroke volume. PMID- 17339755 TI - Effects of leptin and tumor necrosis factor-alpha on degranulation and superoxide production of polymorphonuclear neutrophils from Holstein cows. AB - Leptin, a pleiotropic hormone regulating food intake and energy expenditure, has been shown to directly modulate human polymorphonuclear neutrophil (PMN) functions or indirectly through the action of tumor necrosis factor-alpha (TNF alpha). Bovine PMN have considerable different characteristics from human PMN. For example, it does not respond to N-formyl-Methionyl-Leucyl-phenylalanine, a well known human PMN activator. In the present study, we tested the effects of leptin and TNF-alpha on superoxide production and degranulation of bovine peripheral PMN, in which both long isoform of leptin receptor (Ob-Rb) and TNF receptor 1 were expressed. Human leptin, human TNF-alpha, phorbol myristate acetate (PMA) and opsonized zymosan particles (OZP) did not stimulate degranulation responses, while zymosan-activated serum (ZAS) did. Neither leptin nor TNF-alpha enhanced the ZAS-induced degranulation responses. TNF-alpha, PMA, OZP and ZAS increased superoxide production in different magnitudes, whereas leptin did not. TNF-alpha, but not leptin, enhanced OZP- and ZAS-induced superoxide production, possibly, in part due to facilitating translocation of p47(phox), a component of NADPH oxidase. These results indicate that, unlike in human PMN, leptin does not have any direct effect on degranulation and superoxide production in bovine PMN, although TNF-alpha influences superoxide production. PMID- 17339756 TI - Superoxide dismutase and catalase activities in the seminal plasma of normozoospermic and asthenozoospermic Beagles. AB - We measured the blood plasma testosterone (T) levels and superoxide dismutase (SOD) and catalase activities in the seminal plasma of the ejaculates of 5 normal (2-5 years old) and 5 asthenozoospermic (AZ-) (3-5 years old) Beagles. Sperm ejaculated by AZ-dogs was incubated for 3 hr in Eagle's MEM only (controls) or Eagle's MEM containing 100 units/ml of SOD or catalase. Sperm motility was examined during incubation. The mean (+/- SE) plasma T level of the AZ-dogs (1.2 +/- 0.2 ng/ml) was significantly lower than in the normal dogs (2.5 +/- 0.2 ng/ml) (P<0.005). The mean (+/- SE) seminal plasma SOD and catalase activities (18.8 +/- 1.9 and 0.5 +/- 0.1 unit/g protein, respectively) were significantly lower in the AZ-dogs than in the normal dog (43.3 +/- 2.5 and 2.2 +/- 0.4 unit/g protein, respectively) (P<0.001 and 0.01, respectively). The motility of sperm incubated in Eagle's MEM containing SOD or catalase was significantly higher than that of control sperm incubated in only Eagle's MEM after 2 or 3 hr of incubation (P<0.05). The results of this study indicate that poor T secretion by the testes and low antioxidant enzyme activities are related to AZ in the dog. PMID- 17339757 TI - Trientine, a copper-chelating agent, induced apoptosis in murine fibrosarcoma cells in vivo and in vitro. AB - Anti-copper treatments have been investigated to determine whether they suppress angiogenesis and tumor development since Cu is widely accepted as being required for angiogenesis. We examined the effects of treatment with trientine, a copper chelating agent, on tumor development in a murine xenograft model using fibrosarcoma-derived transplantable QRsp-11 cells and C57BL/6 mice and induction of apoptosis in tumor cells and endothelial cells in vivo and in vitro. The tumor volumes increased more slowly in trientine-treated mice than in untreated mice. Tumor volumes in the treated mice were significantly smaller than those in the untreated mice at 24 days postinoculation (d.p.i.) of tumor cells. A cluster of pyknotic tumor cells and morphological abnormalities in capillary endothelial cells were observed in the tumors of trientine-treated mice but not in the tumors of untreated mice. The proportions of apoptotic and necrotic cells in the tumors of treated mice were approximately 3.5-fold higher than those in the tumors of untreated mice at 14 d.p.i. When the cells were treated with trientine in vitro, mouse endothelial cells and bovine primary endothelial cells showed an approximately 10-fold higher sensitivity to trientine than QRsp-11 cells in terms of D37. However, the proportion of apoptotic cells in endothelial cells was significantly lower than that in QRsp-11 cells after treatment with trientine. These results show that apoptosis was induced in tumor cells by treatment with trientine in vivo and in vitro. PMID- 17339758 TI - Qualitative and quantitative studies of the inferior olivary complex in the water buffalo (Buballus bubalis). AB - The shape and neuronal number of the inferior olivary complex (IOC) were determined in the water buffalo (Buballus bubalis). The configuration and interrelations of the IOC compartments were ascertained by investigating serial sections through the whole rostro-caudal extent of the IOC. Nissl-stained celloidin sections of six water buffalo's brainstems were used. The IOC in the water buffalo consisted of three major nuclei and four small cell groups. The medial accessory olivary nucleus (MAO) had the longest rostro-caudal extent as well as the highest number of neurons (98,000 +/- 3,000). Although the total area of the principal olivary nucleus (PO) was smaller than the area of the dorsal accessory olivary nucleus (DAO), the PO had the second largest neuronal number. The total number of neurons on both sides of the IOC was 210,000 +/- 7,000 cells. The average neuronal density was 3,000 cells/mm3. Although the size of the PO relatively increases while the size of MAO decreases with the development of the cerebellar hemispheres, the IOC in most mammals maintains a similar structure except for the higher primates and marsupials. The water buffalo IOC showed morphological similarities to the almost all mammalian IOC including rats as follow; the main part of the MAO consists of three subgroups (a, b and c), the DAO is Boomerang-shaped while the PO is a simple U-shaped structure. PMID- 17339759 TI - Geographical variation in skull morphology of gray-bellied squirrel Callosciurus caniceps. AB - The geographical variation of the gray-bellied squirrel (Callosciurus caniceps) was examined using osteometry of skull in Southeast Asia. From the principal component analysis (PCA), the plots of the northern localities from Nan to Kanchanaburi and those of the southern localities from Narathiwat to Kuala Lumpur in male were completely separated. In female, the plots of the locality from Uttradit to Kanchanaburi and those of the locality from Pattani to Negri Sembilan were completely separated. We called these northern localities and southern localities which are distinguished by the PCA as N group and S group. The size and shape of the skulls of these squirrels indicated the differences between N group and S group from t-test and U-test. These results may be influenced by the two transitions of the phytogeography around the southernmost locality in N group and the northernmost locality in S group in the peninsular Thailand and Malay Peninsula. Localities which are located between N and S groups were called the Middle (M) group. From the PCA among N, S groups and each locality of M group, the plots of localities such as Prachuap Khiri Khan, Chumphon, Krabi, Nakhon Si Thammarat and Trang in both sexes of M group could not be separated from those of N and S groups. We suggest that the sympatric distribution of N and S groups and the hybrid of N and S populations may be seen in these localities of M group. PMID- 17339760 TI - Genetic uniformity of Echinococcus multilocularis collected from different intermediate host species in Hokkaido, Japan. AB - DNA from several isolates of Taenia taeniaeformis and Echinococcus multilocularis were digested with restriction enzymes and hybridized with digoxigenated oligonucleotide probe (CAC)5. Within the six wild isolates of Taenia taeniaeformis from Norway rats in Hokkaido, although several bands were common among isolates, fingerprinting patterns were specific to each isolate. In the case of E. multilocularis, regardless of hosts from which each isolate has been isolated, the five isolates collected from Hokkaido, showed the same fingerprinting pattern. These results indicate that there was very little genetic difference among these isolates. Although the fingerprinting pattern of E. multilocularis from St. Lawrence Is. was similar to that of the Hokkaido isolates, some bands were different from those in the Hokkaido isolates. Echinococcus multilocularis in Hokkaido seems to be closely-related genetically to that from St. Lawrence Is. PMID- 17339761 TI - Increased number of whistles of bottlenose dolphins, Tursiops truncatus, arising from interaction with people. AB - The acoustic mode is the most reasonable means for social animals such as dolphins to maintain contact in the underwater habitat, and has been developed since they moved to the sea. This study investigates variations in dolphin vocalizations under the following conditions in a captive environment: 1) before feeding (Pre-feeding), 2) during feeding (Feeding), 3) during free time without the presence of people (Free), 4) during interaction with people located upon a float (Float), 5) during interaction with people in the water (Water). During the experiments, a total of 2642 whistles were extracted from sonogram data using a spectrogram. About 44% of the total whistles were observed during Pre-feeding (1171/2642), and the number recorded during Free, when people were absent, was the smallest. The acoustic contours of dolphin whistles differed in different situations: convex, wave, and trill whistles were made repeatedly during Pre feeding, thereby being more common at this time than at other times. The situation of Feeding saw an increased number of Upsweeps, which might be related to the use of echolocation. The lower frequencies were recorded during Pre feeding, reflecting the emotion related to the dolphin's hunger. The results of this study indicate that dolphins increase their vocalization during interaction with people, suggesting that interactions with dolphins provide an effective treatment for human health problems, which is discussed with a reference article in this study. Vocal data obtained during contact with humans might serve as an important index for the dolphin-assisted therapy. PMID- 17339762 TI - Geographical distribution and seasonality of the prevalence of Leucocytozoon lovati in Japanese rock ptarmigans (Lagopus mutus japonicus) found in the alpine regions of Japan. AB - In this study, we investigated the geographical distribution and seasonality of Leucocytozoon lovati infection in the Japanese rock ptarmigan (Lagopus mutus japonicus); this bird is one of the special natural monuments of Japan that inhabits the Japanese alpine regions. We examined blood samples from birds captured in the Kubiki, Hida, and Akaishi mountain ranges for three years from 2002 to 2005. Seventy-three blood samples from 42 males, 19 females, and 12 birds of unknown sex were used for this study. The rate of infection with L. lovati was 78.1% in the 73 birds examined. We demonstrated that the L. lovati infection was distributed across wide ranges of ptarmigan populations from the northern to the southern alpine zones. There was no sex bias in the prevalence ratio. The prevalence of L. lovati and the level of parasitization of the blood cells tended to increase from spring through summer; in contrast, a decrease was observed from summer through autumn. Although L. lovati infection was observed in a number of local populations inhabiting three mountainous regions, no infected birds were found in Mt. Johnen-dake and Mt. Maejohnen-dake. It is necessary to continue surveying the relationship between the population dynamics of the ptarmigan and the density of the arthropod vector from the perspective of in situ conservation of this endangered species. PMID- 17339763 TI - Different patterns of vasoactive intestinal polypeptide (VIP)-immunoreactive and acetylcholinesterase (AChE)-positive innervation in the internal carotid artery and cerebral arterial tree of the quail. AB - The innervation pattern of vasoactive intestinal polypeptide-immunoreactive (VIP IR) nerves in the quail internal carotid artery (ICA) and cerebral arterial tree was investigated and compared with that of acetylcholinesterase-positive (AChE-P) nerves. The supply of VIP-IR nerves to the two arterial systems was distinctly richer than that of AChE-P nerves. It was focused mainly on the walls from the distal ICA to the caudal half of the anterior ramus (AR) through the cerebral carotid artery (CCA). Indeed, double staining clearly showed that numerous VIP+/AChE-axons were distributed over these arterial regions where VIP+/AChE+ or AChE+/VIP- axons were sporadic or often lacking. The finding that nerve bundles accompanying the ICA within the carotid canal contained abundant VIP+/AChE- nerve cells suggests that cerebrovascular VIP-IR nerves in the quail have their major source at these neurons and enter the cranial cavity through the CCA. Another significant finding was that a small number of nerve cells, which were mostly stained for AChE alone and occasionally for VIP alone or both, occurred in the major arteries located more rostral than the middle AR. Thus, the quail cerebral arterial tree, at least the rostral segment of the anterior circulation, is multiply innervated by these three distinct categories of the extracranial and intracranial VIP-IR and AChE-P neurons. PMID- 17339764 TI - Preventive effect of mildly altering dietary cation-anion difference on milk fever in dairy cows. AB - In the present study, we examined whether mildly altering dietary cation-anion difference (DCAD) contributes to the prevention of milk fever in dairy cows. Thirty multiparous cows and ten primiparous cows (heifer group) were used in this study and the multiparous cows were randomly divided into three groups of ten animals each (anion, non-anion and control groups). The cows in the anion group were given supplemental salts that slightly lowered DCAD. These salts consisted of 115 g of CaCO3, 42 g of CaHPO4, 65 g of MgSO4 x 7 H2O and 80 g of CaCl2 x 2 H2O as a daily dose for each cow, using a catheter from 21 days before the expected date of parturition until parturition. The cows in the non-anion group were given only the same Ca, Mg and ip supplement but no sulfate and chloride salts as that in the anion group. The cows in the control and heifer groups were not given any additional supplement. The incidence of hypocalcemia in the anion group decreased to approximately half of those in the non-anion and control groups, while the heifer group did not develop hypocalcemia at all. In addition, the number of days spent for the treatment of hypocalcemia and the number of drug bottles (calcium borogluconate solution) used for the treatment decreased to less than half in the anion group compared with those in the non-anion and control groups. At parturition, the serum Ca concentration in the control (6.2 +/- 1.9 mg/dl, mean +/- standard deviation) and non-anion groups (6.4 +/- 1.7 mg/dl) were significantly lower than that in the heifer group (8.3 +/- 0.4 mg/dl), and the level in the anion group was intermediate (7.3 +/- 1.3 mg/dl). The change in ionized Ca concentration was almost the same as that in serum Ca concentration, but only the concentration in the anion group tended to increase slightly from a week before parturition and was significantly higher than that in all other groups three days before parturition. Urinary pH in the anion group was maintained at a mildly acidic level (6.8-7.0) for the last two weeks before parturition, compared with those in the control (7.3-7.5) and non-anion groups (7.9-8.1), and similar to that in the heifer group (6.3-7.3). The urinary Ca excretion was the highest in the anion group among all groups during the prepartum period. There were no specific changes in the excretion of parathyroid hormone and 1,25-dihydroxyvitamin D in all groups of multiparous cows while the levels of these hormones remained low in the heifer group throughout the experimental period. The data in the present study indicates that the administration of anion salts that slightly lowered DCAD in the preparum period was effective for preventing milk fever in multiparous cows. Safe and mild metabolic acidosis induced by the anion salts could be evaluated by urinary pH (6.8-7.0), and might increase the responsiveness to Ca requirement at parturition through some complex mechanisms unrelated to the excretion of Ca-related hormones. In addition, it was clarified that primiparous cows have a high potential to respond to sudden Ca demand unrelated to hormone excretion, and their Ca metabolism was in some respects similar to that in multiparous cows fed anion salts. Therefore, manipulating mildly DCAD is expected to be an effective, safe and natural method for preventing milk fever in dairy cows. PMID- 17339765 TI - Special sugar expression on apoptotic epithelial cells of Peyer's patches and intestinal villi in rat small intestine. AB - Our previous study clarified that the apical regions of both the follicle associated epithelium (FAE) of Peyer's patches and the intestinal villi are the only adhesion sites of indigenous bacteria in rat jejuno-ileum. To survey the ligands against bacterial lectins, sugar expression patterns on epithelial cells were lectin-histochemically investigated using 21 lectins in the jejuno-ileal Peyer's patches of rats. As a result, (D-glcNAc)(2-4), detected by Solanum tuberosum (STL) and by Lycopersicon esculentum (LEL), and beta-D-gal(1-3)-D galNAc detected by Peanut agglutinin (PNA), were strongly expressed on the brush borders of the apical regions of the FAE and the intestinal villi. On the other hand, neither sugar was expressed on the brush borders of the basal regions of both FAE and intestinal villi. The positive intensities for the lectins correlated with the progression of epithelial apoptosis in the FAE and in the intestinal villi. Moreover, the double staining with lectin histochemical method and the in situ nick end-labeling method could simultaneously detect the strong expression of both sugars and nuclear DNA fragmentation in epithelial cells at the late apoptotic stage. Other sugar expression patterns in the intestinal villi were similar with those in the FAE. There were no lectins specific for M cells in the FAE. From these findings, the possible sugars of ligands against some indigenous bacterial lectins, expressing specially on the apoptotic epithelial cells, might be narrowed down in rat jejuno-ileum. PMID- 17339766 TI - Palliative intravenous cisplatin treatment for concurrent peritoneal and pleural mesothelioma in a dog. AB - A 10-year-old Maltese dog was presented with abdominal distention and dyspnea. Cytological examination of pleural and peritoneal effusion was suggestive of malignant effusion of glandular origin. Numerous, multifocal, tan to white nodules were disseminated throughout the surface of the abdominal organs and peritoneum at biopsy. Histologically, the tumors were revealed to be an epithelial type of mesothelioma. Neoplastic cells co-expressed cytokeratin and vimentin. Intravenous administration of cisplatin was chosen as the treatment. During treatment, the dog's overall body condition improved and the clinical signs were relieved without significant side effects. The survival time from diagnosis to sudden death by unknown cause was 153 days. PMID- 17339767 TI - A new synbiotic consisting of Lactobacillus casei subsp. casei and dextran improves milk production in Holstein dairy cows. AB - To evaluate the effects of a new synbiotic consisting of Lactobacillus casei subsp. casei (Lcc) and dextran (Dex) on milk production, a total of 58 Holstein dairy cows, which became pregnant and gave birth to calves at regular intervals and lactated steadily and continuously, were selected. The study had a completely randomized design, and the animals were divided into two groups. Group A was fed with a basic diet only, and Group B was fed with a basic diet supplemented with the synbiotic consisting of freeze-dried Lcc and mixed feed containing Dex for one year from August 2004. After supplementation with the synbiotic, milk yields and components of Group B were compared with those of Group A in the August, December of 2004, April and August of 2005. Milk yields of Group B were greater than those of Group A. There were significant differences (p<0.01 or 0.05) between these groups for all values. Furthermore, total amounts of fat, protein and solid non-fat in Group B significantly increased in comparison with those of Group A. In addition, the somatic cell counts of Group A significantly increased in August of 2004 and 2005 in comparison with those of Group B. Thus, the new synbiotic consisting of Lcc and Dex can increase the milk production of Holstein dairy cows throughout the year. PMID- 17339768 TI - Hypertrophic osteopathy associated with disseminated metastases of renal cell carcinoma in the dog: a case report. AB - A 6-year-old, mixed breed, intact male dog showed signs of left carpal joint swelling and weakness of the forelimbs one month before presentation. The symptoms gradually progressed to bilateral carpal and tarsal joint swelling and tetraparalysis. There were a number of radiographically identified lytic proliferative bone lesions noted on the axial skeleton. Hypertrophic osteopathy of the metacarpi and all distal long bones was also evident. Because of the deteriorating quality of life and guarded prognosis, the patient was euthanized and a complete necropsy was performed. Renal cell carcinoma, with metastasis to the lung, thoracic vertebrae, ribs, and the right adrenal gland, was diagnosed. To our knowledge, renal cell carcinoma with bone metastases and hypertrophic osteopathy has not been reported in dogs. PMID- 17339769 TI - Effects of reticuloendotheliosis virus and Marek's disease virus infection and co infection on IFN-gamma production in SPF chickens. AB - Two experiments were used to examine the potential role of IFN-gamma in chickens infected with reticuloendotheliosis virus (REV) and Marek's disease virus (MDV). First, chickens were infected with REV and/or MDV at 5 days of age and examined from 3 to 50 days post-infection (dpi). In REV+MDV co-infection chickens, IFN gamma ELISA demonstrated a 3-fold increase at 7 dpi compared to the controls, while REV alone caused a 5-fold increase, the IFN-gamma levels peaked, and then gradually decreased. IFN-gamma levels significantly decreased in MDV infection at 3 dpi and 15 dpi. Second, experiments were designed to determine the effects of different viruses and ConA on IFN-gamma production. For REV- or MDV-infected chickens, the IFN-gamma levels decreased slightly after adding ConA. This is the first report of IFN-gamma production in SPF chickens infected with REV and MDV measured by directly quantitative method. PMID- 17339770 TI - Strong antiviral activity of heated and hydrated dolomite--preliminary investigation. AB - Heated and hydrated naturally occurring dolomite showed very strong antiviral activity. Infectivity of avian and human influenza, avian infectious bronchitis (coronavirus), Newcastle disease (paramyxovirus) and avian laryngotracheitis (herpesvirus) viruses dropped at least 1,000 fold following contact with the dolomite for five minutes at 4 degrees C. Dolomite is expected to be useful to inhibit the incidence of emerging and re-emerging infectious diseases. PMID- 17339771 TI - Anti-influenza A virus activities of mannan-binding lectins and bovine conglutinin. AB - Mannan-binding lectin (MBL) and bovine conglutinin (BKg) belong to the collectin family, which is involved in first-line host defense against various infectious agents. We have previously reported that human MBL inhibited type A influenza viral hemagglutination, infection and spreading to adjacent cells without complement activation. In this study, we investigated the direct antiviral activities of bovine MBL, rabbit MBL and BKg. All collectins used in this study inhibited viral infectivity and hemagglutination at concentrations of 0.02-0.3 microg/ml. They also demonstrated inhibitory activity against viral spreading. Like human MBL, bovine MBL and BKg showed antiviral activities at their physiological concentrations. These results suggest that mammalian MBLs and BKg may inhibit the spread of influenza A virus through the bloodstream. PMID- 17339772 TI - Serum amyloid A levels are increased in pre-eclampsia. AB - AIM: The purpose of this study was to examine serum amyloid A (SAA) levels in normal pregnant and pre-eclamptic women. METHODS: SAA levels were measured in 25 normotensive and 25 pre-eclamptic pregnant women by enzyme linked immuno-sorbent assay. RESULTS: In pre-eclampsia, SAA level and C-reactive protein (CRP) averaged 28.2 (7.2-135) ng/l and 21 (6.13-91) mg/l, respectively, which were significantly higher than those of normal pregnancy (7.8 [4.65-24.6] ng/l and 6.05 [0.3-19] mg/l, respectively) (p < 0.05). In addition, SAA level was positively correlated to CRP (r = 0.468, p < 0.05). CONCLUSION: Marked increases of both SAA level and CRP in pre-eclampsia, and their inter-relation, may at least in part contribute to the pathogenesis of pre-eclampsia. PMID- 17339774 TI - Decreased endothelial progenitor cells in umbilical cord blood in severe preeclampsia. AB - BACKGROUND/AIMS: We compared the numbers of endothelial progenitor cells (EPCs) in umbilical cord blood in severe preeclampsia and normal pregnancy, along with the cord blood plasma levels of free VEGF and sVEGFR-1. METHODS: Umbilical cord blood EPC counts in severe preeclampsia (n = 15) and gestationally matched normal pregnant women (n = 30) were retrospectively analyzed. Cord plasma free VEGF and sVEGFR-1 levels were measured by enzyme immunoassay. RESULTS: Significantly higher systolic blood pressure, lower birth weight, and higher rate of small for gestational age were noted in the severe preeclampsia group. Circulating EPCs in cord blood and umbilical cord plasma free VEGF were significantly decreased in severe preeclampsia compared to the control group (p = 0.009 and 0.04, respectively). CONCLUSION: In severe preeclampsia, cord blood EPCs were reduced markedly and this was accompanied by a significant decrease in cord plasma free VEGF which is known to play a role in EPC mobilization. PMID- 17339775 TI - Prediction of preterm delivery among women with threatened preterm labor. AB - BACKGROUND/AIMS: To determine predictive values of fetal fibronectin and phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) in cervicovaginal secretions and ultrasonographic measurement of cervical length for delivery <35 weeks in patients with uterine contractions. METHODS: Our study included 51 women between 24 and 35 weeks' gestation with uterine contractions and 90 controls. Cervicovaginal samples were analyzed for presence of fetal fibronectin and phIGFBP-1. Cervical length was measured by transvaginal sonography. RESULTS: Preterm birth rate was 19.6% (10/51) in the study group. Negative predictive values of fetal fibronectin, phIGFBP-1 and ultrasonographic cervical length <20 mm, and <25 mm for delivery <35 weeks were 91.9, 92.3, 91.1, and 90.5%, respectively. Positive predictive values were 50, 58.3, 100 and 66.7%, respectively. When results of fetal fibronectin/phIGFBP-1 test and ultrasonographic cervical length <25 mm were combined, specificity and positive predictive values of each test for delivery within 7 days increased. CONCLUSION: Fetal fibronectin and phIGFBP-1 tests have approximately equivalent ability to predict delivery <35 weeks' gestation. An ultrasonographic cervical length measurement >20 mm or a negative fetal fibronectin/phIGFBP-1 test obtained from patients with uterine contractions at 24-35 weeks' gestation may avoid overdiagnosis. PMID- 17339776 TI - Varicella vaccine: A new era of live herpesvirus vaccine. PMID- 17339777 TI - Outpatient percutaneous blind needle liver biopsy: Safety and cost analysis. PMID- 17339778 TI - Pattern of cancer in the United Arab Emirates referred to Al-Ain Hospital. AB - To determine the safety, complication rate and cost saving of outpatient percutaneous blind needle liver biopsy in a single tertiary care center, we retrospectively reviewed the records of all 117 patients who had had outpatient percutaneous blind needle liver biopsy from March 1994 to September 1995. We reviewed data including demography, ChildA centAAs classification, histopathology report and complications, and attempted to compare the cost involved with inpatient liver biopsy. Of the 117 records studied, two were incomplete. Of the 115 patients who had complete records, 43 (37.4%) had minor complications, 2 (1.7%) required overnight hospitalization for pain and hypotension, and the procedure failed in one patient (0.9%). There was no correlation between complications and ChildA centAAs classification, or concomitant chronic renal failure. In comparison to inpatient liver biopsy, we calculated that the saving made is about 1800 Saudi Riyals ($478.70) per operation, if performed on an outpatient basis. We conclude that outpatient percutaneous blind needle liver biopsy is safe, successful in more than 99% of cases, associated with no mortality, has negligible major complications requiring hospital admission, and results in considerable savings per biopsy. We therefore strongly recommend performing most liver biopsies on an outpatient basis, in the appropriate hospital setting, unless hospital admission is otherwise indicated. PMID- 17339779 TI - Prostate cancer in Saudi Arabia: A review of the literature (1975-1996). AB - This paper presents the current available information on prostate cancer in Saudi Arabia. This review of the literature includes most epidemiological studies on cancer in Saudi Arabia that were published in the Saudi medical literature. The reviewed papers presented the experience of medical centers in the Central, Eastern, Western and Southern regions of Saudi Arabia. Papers on prostate cancer that were presented during the annual Saudi Urological Meetings were also analyzed. There was no single paper previously published on this specific cancer in the Saudi medical literature. Four papers related to local experience of prostate cancer were presented in the annual Saudi Urological Conferences, and all reported infrequent encounters with this disease. The data gathered from multiple medical centers in the different regions of the Kingdom indicates that the reported incidence of prostate cancer has been steadily falling in Saudi Arabia over the past 20 years. The information presented here sheds some light on this cancer, and calls for the close observation of any future changes in the frequency of this disease and its related morbidity and mortality. PMID- 17339780 TI - Promotion of non-smoking: The role of primary health care physicians. AB - Cigarette smoking is universally acknowledged to be a health hazard. We are of the opinion that primary health care (PHC) physicians can potentially play a key role in the promotion of non-smoking campaigns. The aim of this study was to determine the role of male PHC physicians in the promotion of a non-smoking campaign among the citizens of Riyadh. About half of the male PHC physicians from Riyadh were selected at random, and were requested to fill an anonymous self administered questionnaire. The content of the questionnaire was validated by three experts and the reliability was excellent, with a CronbachA centAAs alpha of 0.85. The result of the study showed that about 63% of the physicians never smoked, 20% had stopped smoking, and 17% were still smoking an average of 187plusmn;10 cigarettes per day. About 30% of the physicians achieved satisfactory scores, while 7% were reported to play no role in counseling against smoking. During the anti-smoking activity, only 10% of physicians reported making use of religious reasons against smoking. Arab-speaking physicians were shown to be less active than non-Arabs in counseling (P<0.0001), and on-the-job training was found to be associated with better counseling practices (P<0.0221). Our conclusion is that the reported activity of physicians in the promotion of non smoking was far from exemplary, and so was their own smoking profile. There is, therefore, an urgent need to put more emphasis on the promotion of non-smoking among both physicians and patients alike. PMID- 17339781 TI - Follow-up of HIV western blot indeterminate results. AB - Indeterminate results obtained with the Western blot (WB) confirmatory test on HIV enzyme immunoassay (EIA)-positive samples, constituted 15.6% (444/2849) over a 2.5-year period at the referral laboratory for the Western region at the King Fahd General Hospital, Jeddah. Two hundred and fourteen WB-indeterminate samples were followed up by repeat WB testing of subsequent samples from the same patients over a 3-12 month period. One hundred and forty-two samples (66.4%) gave negative results. Sixty-five samples (30%) remained indeterminate. Only seven samples (3.3%) not initially meeting WHO criteria for positivity turned clear-cut positive, with high EIA readings on follow-up. It was discovered initally that a significant proportion of indeterminates was due to low-grade cross-contamination between samples as a result of aerosol backflow during aspiration in the washing procedure. This was eliminated by rinsing the lines between samples, separating samples with high EIA from those with low EIA, and rerunning indeterminate samples. A reduction of indeterminates from 21% to 8.5% subsequently followed. After this improvement, most of the samples that remained indeterminate had low EIA readings, and few bands of mainly anti-gag (p55, p24 or p18) or anti-pol (p51) antibodies, while the few turning positive all had anti-gp160, in addition to anti-p24 or p55. Interestingly, over the last year and a half of the study, 1.4% of the total samples (21/1506) had repeatedly high EIA readings but were negative by WB. In addition, 16 samples (1.1%) were positive for HIV-2. A separate computer-based system for the storage of data was very helpful in ascertaining proper follow-up of indeterminate WB results. PMID- 17339782 TI - Neonatal deaths in the Asir Region of Saudi Arabia: Experience in a Referral Neonatal Intesive Care Unit. AB - We reviewed a total of 169 deaths among 969 infants referred from various health institutions in the Asir Region to the neonatal intensive care unit of Asir Central Hospital, Abha, Saudi Arabia, during a four-year period (January 1992 to December 1995). The results showed that the major causes of neonatal mortality in the region were low birth weight (LBW) (45%), congenital malformations (CM) (30.8%), infection (13.6%), and birth asphyxia (7.7%). The majority of the LBW infants died from respiratory insufficiency, sepsis, and necrotizing enterocolitis. The alimentary, central nervous and cardiovascular systems were the parts most commonly involved in CM, with cardiac defect accounting for the highest fatality rate due to lack of facilities for cardiac surgery in the region, and delay in effecting a transfer. Klebsiella, Serratia and E. coli are the predominant organisms causing neonatal sepsis, in contrast with the group B streptococcus dominating in America and the United Kingdom. Generally, factors causing neonatal deaths in the Asir region are similar to those reported in other tertiary hospitals in Saudi Arabia, and tally closely with observations in America and Europe, where the standard of health care is excellent. Nevertheless, the study indicates the need for upgrading of facilities, as well as for more trained personnel for obstetric and neonatal care in Asir region. It may be necessary to consider the need for the establishment of a regional cardiac surgery center in the region. PMID- 17339783 TI - Aerosolized ribavirin in the treatment of respiratory syncytial viral infection in children: A meta-analysis. PMID- 17339784 TI - Cochlear implantation in deaf children. AB - A cochlear implant (CI) is a hearing device introduced in the 1980s for profoundly deaf subjects who gained little or no benefit from powerful hearing aids. This device comprises an electrode array inserted in the cochlea, connected to an internal receiver, and an externally worn speech processor. The CI transforms acoustic signals into electrical currents which directly stimulate the auditory nerve. Since the early 1990s, cochlear implantation in children has been developing rapidly. Although it is still difficult to predict how a child will perform with a cochlear implant, the success of cochlear implantation can no longer be denied. In this paper, some recent papers and reports, and the results of the various Nijmegen cochlear implant studies, are reviewed. Issues about selection, examinations, surgery and the outcome are discussed. Overall, our results were comparable with those of other authors. It can be concluded that cochlear implantation is an effective treatment for postlingually deaf as well as prelingually (congenital or acquired) deaf children with profound bilateral sensorineural deafness. PMID- 17339785 TI - Strangulation of a small bowel loop caused by a defect in the broad ligament of the uterus. PMID- 17339787 TI - Chronic intussusception. PMID- 17339786 TI - Gardner's syndrome presenting with a giant osteoma. PMID- 17339788 TI - Carcinoma of urinary bladder associated with nephrotic syndrome. PMID- 17339789 TI - Impact of asthma education program on asthma knowledge of general practitioners. PMID- 17339790 TI - Vancomycin-resistant enterococci (VRE) as intestinal flora from poultry in Riyadh. PMID- 17339791 TI - Audit of asthma management in private general practice in Oman. PMID- 17339792 TI - Fracture of the penis: A critique of clinical features and management. PMID- 17339793 TI - Awareness of inborn errors of metabolism among parents in Saudi Arabia. PMID- 17339795 TI - Tumor necrosis factor in falciparum malaria. PMID- 17339794 TI - HTLV-1 Non-Saudi blood donors at King Fahd General Hospital, Jeddah. PMID- 17339796 TI - Reply: Tumor necrosis factor in falciparum malaria. PMID- 17339797 TI - Frequencies of a C-T mutation in lipoprotein lipase and a G-A mutation in Alipoprotein-A1 in Saudi Arabia. PMID- 17339798 TI - The role of ultrasonography and ultrasound-guided aspiration in blunt abdominal trauma. PMID- 17339799 TI - Reply: The role of ultrasonography and ultrasound-guided aspiration in blunt abdominal trauma. PMID- 17339801 TI - Rapid diagnosis of Mycobacterium tuberculosis by Amplicor PCR and LCR in a Clinical Laboratory. PMID- 17339800 TI - The spectrum of diffuse and focal liver lesions in workers exposed to vinylchloridemonomer. PMID- 17339806 TI - [Physical activity and sleep patterns in elderly who visited a community senior center]. AB - PURPOSE: The purpose of this study was to identify the relationship between physical activity and sleep patterns of the elderly. METHODS: The subjects of this study were 154 elderly who visited a community senior center in Korea. Data was collected by an interview and a self reported questionnaire, during the period from June to October, 2006. Physical activity was measured by IPAQ Korean version (2006), and sleep pattern by Korean Sleep Scale A developed by Oh et al. (1998). RESULTS: The prevalence of chronic illness in the subjects was 73.4 %. The mean time of vigorous activity was 6.62+/-31.27 minutes/day during the past week. Moderate activity time was 28.85+/-50.31 minutes/day and walking time was 28.85+/-50.3 minutes/day. The total sleep time was 397.63+/-111.53 minutes/day. Physical activity of the elderly significantly correlated with sex, chronic illness, job, and sleep patterns of the elderly. Stepwise multiple regression analysis revealed that the most powerful predictor of sleep pattern was the satisfaction of sleep. A combination of the number of chronic illnesses, moderate physical activities (MET), and total time of sleep accounted for 44.4% of the sleep pattern. CONCLUSIONS: Moderate physical activity is more effective than vigorous physical activity for improving the sleep quality of the elderly. PMID- 17339807 TI - [Development of a user centered web site for mental health management in adolescents]. AB - PURPOSE: A user centered web-based mental health management system may be particularly useful in Korea where there is widespread diffusion of personal computers and internet connectivity. The purpose of this paper was to describe the development of a web-based system for mental health management in adolescents using principals of a user centered design. METHOD: Our design process includes five distinct phases: needs assessment, analysis, design, development/testing/revision, and application release. RESULTS: Web content includes an introduction, information about mental health management in adolescents, self-assessment and guidance, interventions for improving mental health, directory of self-help groups, and counseling and additional community resources. The web site was released using the URL: http://www.baejy.com/youth. CONCLUSION: The end result was a web based mental health management system for adolescents with a high degree of usability. The author believes that web-based mental health interventions in the future have true potential in helping Koreans who are suffering, or at risk, for mental health problems, particularly because of the stigma related to psychiatric therapy in Korea. PMID- 17339808 TI - [Family experiences of living with chronic schizophrenic patients - application of Parse's human becoming research methodology]. AB - PURPOSE: This study was aimed at understanding the nature of the suffering of families with patients in mental health nursing homes and hoped to contribute to the rehabilitation process of those with a chronic mental disorder. METHOD: Research methodology was based upon Parse's human becoming research methodology. RESULTS: a) Despite the despair the family feels by the violence caused by their now-institutionalized relative, they also realize anew the importance of their role as protectors b) Although they fear social stigmatization they also try to be supportive, out of guilt feelings; c) They regret their severe rearing style and wish to be more sympathetic, d) They find courage and hope through family therapy, which leads to a better understanding of the illness, e) With hopes of rehabilitation, the family members feel happy and go through an emotional release, by sharing the pain with each other. CONCLUSION: Families of nursing home residents share a focus on the process of human-health-universe. This is a positive, 'human-becoming' process with which, based on past feelings of despair, fear, resignation, and pain, one can render meaning into his or her experiences in the present in the pursuit of love, conquest, hope, liberty and success. PMID- 17339809 TI - [Alcohol experience, alcohol knowledge, and alcohol expectancy in early adolescents]. AB - PURPOSE: This study was to explore the prevalence of alcohol experiences and to identify the expectancy on the effects of alcohol and alcohol knowledge in early adolescents. METHOD: The cross-sectional survey of 1854 students from seven middle schools in one district of Seoul was conducted by convenience sampling. Alcohol experience and early onset of alcohol use were measured by the Youth Risk Behavior Survey. Alcohol expectancy was measured by an Alcohol Effects Questionnaire. RESULT: Over sixty five percent of adolescents reported that they had previous drinking experiences. The participants with no alcohol drinking experience had a lower level of alcohol knowledge than those with experience(t=2.73, p=.007). In expectancy on effects of alcohol, girls had a more positive alcohol expectation than boys(t=-2.54, p=.011). Alcohol knowledge negatively correlated with alcohol expectancy(r=-.40 p=.000). In regression of alcohol expectancy, gender and alcohol knowledge were significant predictors explaining 17%. CONCLUSION: The results support that alcohol expectancy is an important link with early drinking experiences and alcohol knowledge, focusing on the importance of gender differences. Therefore, an alcohol prevention program in early adolescence is needed and should be focused on multidimensionality of the alcohol expectancy with developmental and psychosocial factors for early adolescents. PMID- 17339810 TI - [A study on regional differentials in death caused by suicide in South Korea]. AB - PURPOSE: The purpose of this study was to compare suicide mortality by region in South Korea. METHOD: Suicide mortality differentials were calculated for several mortality indicators by geographical regions from raw data of the cause of death from KNSO. RESULTS: The results are as follows; the Crude suicide death rate was 22.63 per 100,000. The highest was in Kangwon showing 37.84% whereas, Chungnam, and Jeonbuk followed after. Suicide was 4.4% of all causes of death, but Inchon and Ulsan showed a higher proportion. The male suicide death rate was 31.12 per 100,000 and females 14.09. The ratio of gender suicide mortality was 2.21, per 100,000 and was the highest in Jeju. For age-specific suicide death rates, the rate increased as age advanced, showing 2.33 per 100,000 in 0-19 years, 18.68 in 20-39, 30.48 in 40-59,63.33 in 60 years and over. In Ulsan, Kangwon, and Inchon, age-specific suicide death rates of the 60 and over age group were higher than other regions, Daegu, Busan, and Kangwon showed a higher age-specific suicide mortality of the 40-59 age group, and Kangwon, Jeonnam, and Chungnam had a higher age-specific suicide mortality of the 20-39 age group. CONCLUSIONS: Suicide mortality differed by region. These results can be used for a regional health care plan and planning for suicide prevention by regions. PMID- 17339811 TI - [Functional phases and patterns of dialogue sequence in nurse-patient conversation about medication]. AB - PURPOSE: Effective communication is an essential aspect of nursing care. This qualitative study was performed to analyze nurse-patient conversations about medication. METHOD: The nurse-patient dialogue was collected by video tape recording during the nurse's duty time in an internal medicine ward. One hundred seventy-eight episodes were extracted from the conversation. Using conversational analysis, the functional phases and patterns of dialogue sequence pertaining to medication were analyzed. RESULTS: Conversations about medication were very brief dialogues, so 68.8% of the dialogue had a duration of less than 20 seconds. However, it was a systematic and comprehensive dialogue which had structures and sequential dialogue patterns. Four functional phases were explored: greeting, identifying the patient, medicating, finishing. The medicating phase was essential, in which the nurse gave the drug to the patient and provided information initiated by the nurse simultaneously. The patterns of the dialogue sequence represented were the nurse provided information first, and then, patients responded to the nurse as accepting, rejecting, raising an objection, or asking again later. CONCLUSION: As the results of this study show, a nurse's role is important as an educator. For effective conversation about medication, the development of an educational program should be considered, which includes knowledge about medication and communication skills. PMID- 17339812 TI - [The life of patients with a heart transplant]. AB - PURPOSE: The main purpose of this study was to develop a substantive theory on the life of patients with heart transplantation in the context of Korean society and culture. The question for the study was "What is the life of patients like with a heart transplant?". METHOD: A grounded theory method guided the data collection and analysis. Participants for this study were 12 adults who regularly visited a Cardiovascular ambulatorium in a medical center. The data was collected through an in-depth interview and analyses were performed simultaneously. RESULT: 'Developing a new life to live on borrowed time' was the core category in this study. It revealed two types of life, one is living in peace and another is thinking positive. CONCLUSION: This study provides a framework for the development of individualized nursing interventions to care for patients with Heart Transplantation. The findings may provide pointers for health professionals about ways to improve support for heart transplant recipients. PMID- 17339813 TI - [The analysis of intervention studies for patients with metabolic syndrome]. AB - PURPOSE: This study was to analyze the trend of research on intervention for patients with metabolic syndrome. METHOD: Using Pubmed, Medline, and CINAHL search engines, a randomized controlled trial(RCT) researching titles such as "metabolic syndrome", "intervention", "lifestyle modification", or "community based" were collected. A total of 16 researches were analyzed based on the guidelines of the National Cholesterol Education Program-Adult Treatment Panel(NCEP-ATP III). RESULTS: 1) The total period of the intervention was from 12 to 24 weeks, the frequency was 3 to 5 times per week, and the duration of each session was from 45 to 60 minutes. The types of intervention included exercise, diet, and medication. Among these types, diet was performed most frequently. 2) The outcomes of the intervention was measured with physical aspects such as anthropometric measures, body composition, or biological markers. No studies have evaluated psychosocial outcomes such as quality of life. 3) In terms of effectiveness of the intervention, anthropometric indicators, body composition, or serological markers showed positive effects, whereas results on endothelial or urine indicators were inconsistent. CONCLUSION: Methodological research developing comprehensive therapeutic lifestyle modification programs and intervention studies are needed for patients with metabolic syndrome. In addition, effects should be evaluated with multidimensional perspectives. PMID- 17339814 TI - [Effects of exercise before steroid treatment on type i and type ii hindlimb muscles in a rat model]. AB - PURPOSE: The purpose of this study was to examine the effects of daily exercise before steroid treatment on mass, the type I and II fiber cross-sectional area, and myofibrillar protein content of hindlimb muscles in a rat model. METHOD: Adult male Sprague-Dawley rats were randomly assigned to one of three groups: a control group(n=10) that had a normal saline injection for 7 days, a steroid group(n=10) that had a steroid injection for 7 days, and an exercise-steroid group(n=10) that ran on the treadmill for 7 days before a steroid treatment. Body weight and food intake were measured every day. At 15 days all rats were anesthetized and the soleus, plantaris and gastrocnemius muscles were dissected. RESULT: The exercise-steroid group showed significant increases as compared with the steroid group in body weight, muscle weight of the soleus and gastrocnemius, type II muscle fiber cross-sectional area of plantaris, and myofibrillar protein content of the soleus, plantaris, and gastrocnemius. As compared with the control group, the steroid group showed significant decreases in body weight and diet intake, muscle weight, the type II fiber cross-sectional area and myofibrillar protein content of the soleus, plantaris, and gastrocnemius muscles. CONCLUSION: Daily exercise before steroid treatment attenuates hindlimb muscle atrophy, with type II muscle changes more apparent than type I muscle changes. PMID- 17339815 TI - [Parenting experiences of parents of children with ADHD: approaching the normal]. AB - PURPOSE: The purpose of this study was to explore the experiences of parenting from the parents of children with ADHD and to develop a grounded theory about their experiences. METHOD: This study was a qualitative research study that used a grounded theory to understand and discuss the parenting experiences of parents of children with ADHD in a greater depth. Grounded data was collected through an in-depth interview from twelve participants with ADHD children. The data was analyzed using the grounded theory method. RESULTS: "Approaching the normal" emerged as the core phenomenone. Parenting experiences for parents of children with ADHD referred to a process of bringing the children, back on track of normal growth development, and their functioning in the family at a normal level and establishing a new normalcy. The process of approaching the normal involved a basic social-psychological process, such as 'living a day in hell', 'accepting', 'confronting the conflicts', 'lowering expectations', and 'making a new normalcy'. CONCLUSION: The outcomes of this study, which observed the parenting process of parents of children with ADHD, could enhance nurses' understanding of ADHD and help nurses become major mental health service providers for the mental health of children with ADHD and their families. PMID- 17339816 TI - [The effects of a multi agent obesity control program in obese school children]. AB - PURPOSE: The purpose of this study was to identify the effects of a multi agent obesity control program in obese school children. This program was composed of strategies to modify diet and exercise habits and to change cognitive behavior variables(stress, coping, and self-efficacy). METHOD: The subjects were 40 obese school children who participated in our project voluntarily via homepage, TV, newspaper, public paper and school official documents. The program was implemented daily for 4 sessions per day for ten days from August 16 to 26, 2004. The daily program consisted of exercise therapy, dance therapy, cognitive behavior therapy and aroma therapy. The data was analyzed by paired t-test using the SPSSWIN program. RESULT: There was a significant decrease in children's waist hip ratio (p=.04) and in children's stress (p=.00) after the program. There was a significant increase in children's self-confidence after the program(p=.02) and a significant decrease in children's diet habit after the program(p=.02). CONCLUSION: This study provides evidence that a multiagent obese control program is effective in changing waist-hip ratio, stress, self-confidence, and diet habits in obese school children. PMID- 17339817 TI - [Experience of job satisfaction in clinical nurses: application of focus group methodology]. AB - PURPOSE: The purpose of this study was to describe the experiences of job satisfaction in clinical nurses. METHODS: Data was collected from three focus groups composed of 17 hospital nurses. Each focus group had an interview for an average of two and a half hours with the guidance of researchers. The main question was "how do you describe your lived experience of job satisfaction as a clinical nurse?" Qualitative data from the field notes and transcribed notes were analyzed using a grounded theory methodology developed by Strauss and Corbin. RESULTS: The core category of experience of job satisfaction in clinical nurses was identified as "Finding success." Supportive interpersonal relationships and environment affected this category. In the process of attaining job satisfaction through finding success, the participants were using four interactional strategies such as giving meaning, finding self-esteem, extending the horizon of life, and strengthening self-capability. The dimensions of job satisfaction in clinical nurses were the sense of achievement, stability, and pride. CONCLUSION: The results of this study yields very useful information for nursing managers to design a program which enhances job satisfaction of clinical nurses based on interactional strategies. PMID- 17339818 TI - [Effects of a newborn care education program on newborn care confidence and behavioral accuracy of primiparas in a postpartum care center]. AB - PURPOSE: The study aimed to identify the effects of a newborn care education program on newborn care confidence and behavioral accuracy of primiparas in a postpartum care center. METHOD: This was a quasi-experimental study with a non equivalent control group non-synchronized design. Subjects were 29 primiparas selected from a postpartum care center in D and P hospitals in Ulsan. The intervention was a newborn care education program which was composed of education with a booklet, demonstration, watching a video, and verbal encouragement. The outcome variables were newborn care confidence and behavioral accuracy. Data was collected from Feb. 1 to Mar 22 in 2005 with self-administered questionnaires and observation by researchers. Data was analyzed using the chi(2)-test, Fisher's exact test, t-test and ANCOVA. RESULT: The experimental group showed significantly higher score changes between the pre-test and post-test in confidence and behavioral accuracy than the control group. CONCLUSION: The newborn care education program showed positive effects on newborn care confidence and behavioral accuracy of primiparas in a postpartum care center. Therefore, we recommend that this program should be applied in postpartum care centers. PMID- 17339819 TI - [Activities of daily living of the elderly with a chronic disease and burden on family care-givers]. AB - PURPOSE: The purpose of this study was to help families decrease and alleviate the burden on family care-givers taking care of elderly patients. METHOD: Data was collected by a questionnaire from 100 family members who were registered in the department of home health care nursing at 4 hospitals of H University Medical Center from September 20 to October 25, 2005. The collected data was analyzed using Mean and Standard Deviation, Pearson Correlation Coefficient, t-test and One-Way ANOVA with the Duncan's test, and Stepwise multiple regression. RESULT: The average burden on family care-givers of elderly patients with chronic diseases was 3.31. The social burden was the highest(M=3.68), the lowest was the emotional burden (M=2.95). In ADL of elderly patients with chronic diseases, all 10 questions showed an average point above 2.50. The dependency level of going up and down the stairs was the highest (M=2.88). CONCLUSION: This research is necessary for the application of a plan in the social support system in order to reduce the burden on family care-givers who are taking care of elderly patients with a chronic disease. PMID- 17339820 TI - [A conversational analysis about patient's discomfort between a patient with cancer and a nurse]. AB - PURPOSE: The purpose of this study was to describe and to analyze real communication about a patient's discomfort between a patient with cancer and a nurse. METHOD: A dialogue analysis method was utilized. Fifteen patients and 4 nurses who participated in this research gave permission to be videotaped. The data was collected from January, 3 to February 28, 2006. RESULTS: The communication process consisted of 4 functional stages: 'introduction stage', 'assessment stage', 'intervention stage' and 'final stage'. After trying to analyze pattern reconstruction in the 'assessment stage' and 'intervention stage', sequential patterns were identified. In the assessment stage, if the nurse lead the communication, the sequential pattern was 'assessment question answer' and if the patient lead the communication, it was 'complaint-response'. In the intervention stage, the sequential pattern was 'nursing intervention acceptance'. CONCLUSION: This research suggests conversation patterns between patients with cancer and nurses. Therefore, this study will provide insight for nurses in cancer units by better understanding communication behaviors. PMID- 17339821 TI - E2902: A Phase III randomized study of farnesyl transferase inhibitor R115777 in acute myeloid leukemia patients in second or subsequent remission or in remission after primary induction failure or patients over age 60 in first remission. PMID- 17339822 TI - Advances in CLL. PMID- 17339823 TI - Managing cancer-related symptoms: advances in supportive oncology. PMID- 17339824 TI - Newly approved therapies for RCC and their effect on the standard of care. PMID- 17339825 TI - The genomics and Personalized Medicine Act of 2006. PMID- 17339826 TI - Thrombocytopenia in pregnancy. PMID- 17339827 TI - An overview of integrative oncology. PMID- 17339828 TI - Chronic anemia due to parvovirus B19 infection in a patient with multiple myeloma. PMID- 17339829 TI - Therapeutic advances in the treatment of brain metastases. AB - Brain metastases are a frequent sequelae of many solid tumors. Whole-brain radiotherapy (WBRT) has been the standard treatment for decades, with modest long term complications observed using doses no greater than 3 Gy/fraction. Surgical resection may be beneficial in select populations of patients with single brain metastases, controlled systemic disease, and good performance status. Radiosurgery has demonstrated consistent improvement in local control, with some reports showing a survival benefit when combined with WBRT. However, the role of radiosurgery as a single modality is unclear, particularly given concerns that higher rates of distant brain relapse result in increased risk of neurologic compromise and death from neurologic causes. Increasingly, the importance of neurocognitive assessment with brain metastases is being recognized, and recent data have strongly correlated neurocognitive dysfunction with tumor progression. Systemic agents showing activity in brain metastases including temozolomide, RSR13, motexafin gadolinium, and lapatinib are being explored. PMID- 17339830 TI - Direct labelling of the human P2X7 receptor and identification of positive and negative cooperativity of binding. AB - BACKGROUND AND PURPOSE: The P2X(7) receptor exhibits complex pharmacological properties. In this study, binding of a [(3)H]-labelled P2X(7) receptor antagonist to human P2X(7) receptors has been examined to further understand ligand interactions with this receptor. EXPERIMENTAL APPROACH: The P2X(7) receptor antagonist, N-[2-({2-[(2-hydroxyethyl)amino]ethyl}amino)-5-quinolinyl]-2 tricyclo[3.3.1.1(3,7)]dec-1-ylacetamide (compound-17), was radiolabelled with tritium and binding studies were performed using membranes prepared from U-2 OS or HEK293 cells expressing human recombinant P2X(7) receptors. KEY RESULTS: Binding of [(3)H]-compound-17 was higher in membranes prepared from cells expressing P2X(7) receptors than from control cells and was inhibited by ATP suggesting labelled sites represented human P2X(7) receptors. Binding was reversible, saturable and modulated by P2X(7) receptor ligands (Brilliant Blue G, KN62, ATP, decavanadate). Furthermore, ATP potency was reduced in the presence of divalent cations or NaCl. Radioligand binding exhibited both positive and negative cooperativity. Positive cooperativity was evident from bell shaped Scatchard plots, reduction in radioligand dissociation rate by unlabelled compound-17 and enhancement of radioligand binding by KN62 and unlabelled compound-17. ATP and decavanadate inhibited binding in a negative cooperative manner as they enhanced radioligand dissociation. CONCLUSIONS: These data demonstrate that human P2X(7) receptors can be directly labelled and provide novel insights into receptor function. The positive cooperativity observed suggests that binding of compound-17 to one subunit in the P2X(7) receptor complex enhances subsequent binding to other P2X(7) subunits in the same complex. The negative cooperative effects of ATP suggest that ATP and compound-17 bind at separate, interacting, sites on the P2X(7) receptor. PMID- 17339831 TI - Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB 429) in a mouse model of colitis. AB - BACKGROUND AND PURPOSE: Mesalamine is the first-line therapy for colitis, but it lacks potency and is only effective for mild-to-moderate forms of this disease. Hydrogen sulphide has been shown to be a potent, endogenous anti-inflammatory substance, modulating leukocyte-endothelial adhesion and leukocyte migration. The purpose of this study was to determine if an H(2)S-releasing derivative of mesalamine (ATB-429) would exhibit increased potency and effectiveness in a mouse model of colitis. EXPERIMENTAL APPROACH: Colitis was induced in mice with trinitrobenzene sulphonic acid and the effects of ATB-429 and mesalamine were compared in several treatment regimens. The severity of colitis was determined using several indices, including a disease activity score (comprised of scores for diarrhea, weight loss and fecal blood), colonic myeloperoxidase activity and macroscopic/microscopic scoring of tissue injury. KEY RESULTS: Irrespective of the treatment regiment, ATB-429 was more effective than mesalamine in reducing the severity of colitis. ATB-429 was particularly effective in reducing granulocyte infiltration into the colonic tissue (by approximately 70%), as well as reducing the expression of mRNA for several key proinflammatory cytokines/chemokines (e.g., TNFalpha, IFNgamma). Treatment with ADT-OH, the H(2)S releasing moiety of ATB-429, did not affect severity of colitis. CONCLUSIONS AND IMPLICATIONS: ATB-429 exhibits a marked increase in anti-inflammatory activity and potency in a murine model of colitis, as compared to mesalamine. These results are consistent with recently described anti-inflammatory effects of H(2)S. ATB-429 may represent an attractive alternative to mesalamine for the treatment of inflammatory bowel disease. PMID- 17339832 TI - Stimulatory action of protein kinase C(epsilon) isoform on the slow component of delayed rectifier K+ current in guinea-pig atrial myocytes. AB - BACKGROUND AND PURPOSE: Protein kinase C (PKC) comprises at least twelve isoforms and has an isoform-specific action on cardiac electrical activity. The slow component of delayed rectifier K(+) current (I (Ks)) is one of the major repolarizing currents in the hearts of many species and is also potentiated by PKC activation. Little is known, however, about PKC isoform(s) functionally involved in the potentiation of I (Ks) in native cardiac myocytes. EXPERIMENTAL APPROACH: I (Ks) was recorded from guinea-pig atrial myocytes, using the whole cell configuration of patch-clamp method. KEY RESULTS: Bath application of phenylephrine enhanced I (Ks) concentration-dependently with EC(50) of 5.4 microM and the maximal response (97.1+/-11.9% increase, n=16) was obtained at 30 microM. Prazosin (1 microM) almost totally abolished the potentiation of I (Ks) by phenylephrine, supporting the involvement of alpha(1)-adrenoceptors. The stimulatory action of phenylephrine was significantly, if not entirely, inhibited by the general PKC inhibitor bisindolylmaleimide I but was little affected by Go 6976, Go-6983 and rottlerin. Furthermore, this stimulatory effect was significantly reduced by dialyzing atrial myocytes with PKCepsilon-selective inhibitory peptide epsilonV1-2 but was not significantly affected by conventional PKC isoform-selective inhibitory peptide betaC2-4. Phorbol 12-myristate 13 acetate (PMA) at 100 nM substantially increased I (Ks) by 64.2+/-1.3% (n=6), which was also significantly attenuated by an internal dialysis with epsilonV1-2 but not with betaC2-4. CONCLUSIONS AND IMPLICATIONS: The present study provides experimental evidence to suggest that, in native guinea-pig cardiac myocytes, activation of PKC contributes to alpha(1)-adrenoceptor-mediated potentiation of I (Ks) and that epsilon is the isoform predominantly involved in this PKC action. PMID- 17339834 TI - Characterization of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to GABAA receptors in postmortem human brain. AB - BACKGROUND AND PURPOSE: The aim of the present study was to determine whether binding of [(35)S]t-butylbicyclophosphorothionate ([(35)S]TBPS) to the convulsant binding site of GABA(A) receptors in human postmortem brain samples can be used as an in vitro index of the functional activation of these receptors. EXPERIMENTAL APPROACH: Postmortem stability of [(35)S]TBPS binding was assessed in rat brain samples harvested at various times after death and the binding properties of [(35)S]TBPS binding (K(D) and B(max)) were determined in human postmortem brain using radioligand binding studies. In addition, the ability of human brain [(35)S]TBPS binding to be allosterically modulated by compounds that bind at recognition sites distinct from the convulsant binding site was measured. KEY RESULTS: Whereas binding of [(3)H]Ro 15-1788 to the benzodiazepine binding site and [(3)H]muscimol to the agonist (GABA) binding site were retained over a 20 h postmortem interval, there was a significant decrease in the affinity and number of [(35)S]TBPS binding sites. Nevertheless, [(35)S]TBPS binding in human brain could be inhibited by TBPS, picrotoxin, loreclezole and pentobarbital and modulated by GABA with potencies comparable to those observed in rats. In addition, the GABA-induced reduction in human brain [(35)S]TBPS binding could be modulated by benzodiazepine site ligands in a manner that reflected their intrinsic efficacies. CONCLUSIONS AND IMPLICATIONS: These results suggest that allosteric coupling between the [(35)S]TBPS, GABA and benzodiazepine binding sites is preserved in postmortem human brain and that [(35)S]TBPS binding in this tissue may be used to study functional characteristics of native human GABA(A) receptors. PMID- 17339833 TI - Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer. AB - BACKGROUND AND PURPOSE: Two mechanisms have been proposed to explain the insulin sensitising properties of metformin in peripheral tissues: (a) inhibition of electron transport chain complex I, and (b) activation of the AMP activated protein kinase (AMPK). However the relationship between these mechanisms and their contribution to beta-cell death and dysfunction in vitro, are currently unclear. EXPERIMENTAL APPROACH: The effects of biguanides (metformin and phenformin) were tested on MIN6 beta-cells and primary FACS-purified rat beta cells. Cell metabolism was assessed biochemically and by FACS analysis, and correlated with AMPK phosphorylation state and cell viability, with or without fuel substrates. KEY RESULTS: In MIN6 cells, metformin reduced mitochondrial complex I activity by up to 44% and a 25% net reduction in mitochondrial reducing potential. In rat beta-cells, metformin caused NAD(P)H accumulation above maximal glucose-inducible levels, mimicking the effect of rotenone. Drug exposure caused phosphorylation of AMPK on Thr(172) in MIN6 cell extracts, indicative of kinase activation. Methyl succinate, a complex II substrate, appeared to bypass metformin blockade of complex I. This resulted in reduced phosphorylation of AMPK, establishing a link between biguanide-induced mitochondrial inhibition and AMPK activation. Corresponding assessment of cell death indicated that methyl succinate decreased biguanide toxicity to beta-cells in vitro. CONCLUSIONS AND IMPLICATIONS: AMPK activation can partly be attributed to metformin's inhibitory action on mitochondrial complex I. Anaplerotic fuel metabolism via complex II rescued beta-cells from metformin-associated toxicity. We propose that utilisation of anaplerotic nutrients may reconcile in vitro and in vivo effects of metformin on the pancreatic beta-cell. PMID- 17339835 TI - Physiological activities of carbon monoxide-releasing molecules: Ca ira. AB - In this issue of British Journal of Pharmacology, Megias and colleagues demonstrate how preincubation of human colonic Caco-2 cells with CORM-2, a carbon monoxide releasing molecule (CO-RM), reduces the expression of inducible nitric oxide synthase, interleukin (IL)-6 and IL-8 caused by proinflammatory cytokines. A role for IL-6 in the regulation of metalloproteinase (MMP)-7 expression by CORM 2 is described. However, it is the demonstration that CORM-2 inhibits MMP-7 or matrilysin expression, which is most intriguing as this small MMP has been implicated in carcinogenesis. Thus, CO-RMs appear to now possess chemoprotective properties and, in this particular case, may influence inflammation-induced colon carcinogenesis via modulation of nuclear factors participating in the transcription of genes implicated in the development of intestinal inflammation and cancer. This report opens yet another door for research involving these exciting molecules and it is now clear that further discoveries of the beneficial properties of CO-RMs will go on. PMID- 17339836 TI - The carbon monoxide-releasing molecule CORM-2 inhibits the inflammatory response induced by cytokines in Caco-2 cells. AB - BACKGROUND AND PURPOSE: Recent evidence indicates that carbon monoxide-releasing molecules (CO-RMs) exhibit potential anti-inflammatory properties. In the present study, we have investigated whether tricarbonyl dichloro ruthenium(II) dimer (CORM-2) can control the inflammatory response induced by cytokines in a human colonic epithelial cell line, Caco-2. EXPERIMENTAL APPROACH: Caco-2 cells were preincubated with CORM-2 for 30 minutes and then stimulated with interleukin (IL) 1beta, tumor necrosis factor-alpha and interferon-gamma for different times. Gene expression was analyzed by real-time PCR. Protein expression was investigated by Western blot and ELISA. Transcription factor activation was determined by the luciferase method. KEY RESULTS: We have shown that CORM-2 significantly decreased the mRNA expression of nitric oxide synthase-2 (NOS-2) and the production of nitrite, in Caco-2 cells stimulated with cytokines. IL-8, IL-6 and metalloproteinase-7 (MMP-7) mRNA and protein were also significantly reduced by CORM-2. Time-course and small interfering RNA studies suggest that inhibition of IL-6 plays a role in the regulation of MMP-7 expression by CORM-2. These effects of CORM-2 can be dependent on the modulation of nuclear factor-kappaB (NF kappaB), activator protein-1, CCAT/enhancer binding protein and the phosphorylated forms of NF-kappaB inhibitory protein-alpha, c-Jun N-terminal protein kinase 1/2, p38 and extracellular signal-regulated kinase 1/2. CONCLUSIONS AND IMPLICATIONS: CORM-2 can regulate a number of genes relevant in intestinal inflammation and cancer progression. These findings provide new insights into the anti-inflammatory properties and potential applications of this class of compounds. PMID- 17339837 TI - Heparanase: a target for drug discovery in cancer and inflammation. AB - The remodelling of the extracellular matrix (ECM) has been shown to be highly upregulated in cancer and inflammation and is critically linked to the processes of invasion and metastasis. One of the key enzymes involved in specifically degrading the heparan sulphate (HS) component of the ECM is the endo-beta glucuronidase enzyme heparanase. Processing of HS by heparanase releases both a host of bioactive growth factors anchored within the mesh of the ECM as well as defined fragments of HS capable of promoting cellular proliferation. The finding that heparanase is elevated in a wide variety of tumor types and is subsequently linked to the development of pathological processes has led to an explosion of therapeutic strategies to inhibit its enzyme activity. So far only one compound, the sulphated oligosaccharide PI88, which both inhibits heparanase activity and has effects on growth factor binding has reached clinical trials where it has shown to have promising efficacy. The scene has clearly been set however for a new generation of compounds, either specific to the enzyme or with dual roles, to emerge from the lab and enter the clinic. The aim of this review is to describe the current drug discovery status of small molecule, sugar and neutralising antibody inhibitors of heparanase enzyme activity. Potential strategies will also be discussed on the selection of suitable biomarker strategies for specific monitoring of in vivo heparanase inhibition which will be crucial for both animal model and clinical trial testing. PMID- 17339838 TI - Endothelial dysfunction and compromised eNOS/Akt signaling in the thoracic aorta during the progression of Marfan syndrome. AB - BACKGROUND AND PURPOSE: Aortic complications account for the major mortality in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in FBN1 encoding fibrillin-1. We hypothesized that MFS impaired endothelial function and nitric oxide (NO) production in the aorta. EXPERIMENTAL APPROACH: Mice (at 3, 6, 9 and 12 months of age) heterozygous for the Fbn1 allele encoding a cysteine substitution (Fbn1 (C1039G/+), Marfan mice, n=75), the most common class of mutation in MFS, were compared with age-matched control littermates (n=75). Thoracic and abdominal aortas from the two groups were studied. KEY RESULTS: Isometric force measurements revealed that relaxation to ACh (but not to sodium nitroprusside) was diminished in the phenylephrine-precontracted Marfan thoracic aorta at 6 months of age (pEC(50)=6.12+/-0.22; maximal response, E(max)=52.7+/ 6.8%; control: pEC(50)=7.34+/-0.19; E(max)=84.8+/-2.2%). At one year, both inhibition of NO production with N(omega)-nitro-L-arginine methyl ester, or denudation of endothelium increased the phenylephrine-stimulated contraction in the control thoracic aorta by 35%, but had no effect in the Marfan aorta, indicating a loss of basal NO production in the Marfan vessel. From 6 months, a reduced phosphorylation of endothelial NOS (eNOS)(Ser1177) and Akt(Thr308) detected by Western blotting was observed in the Marfan thoracic aorta, which was accompanied by decreased levels of cGMP. Expressions of Akt and eNOS in the abdominal aorta were not different between the two groups. CONCLUSIONS AND IMPLICATIONS: MFS impairs endothelial function and signaling of NO production in the thoracic aorta, suggesting the importance of NO in the age-related progression of thoracic aortic manifestations. PMID- 17339840 TI - Chloride transporting capability of Calu-3 epithelia following persistent knockdown of the cystic fibrosis transmembrane conductance regulator, CFTR. AB - BACKGROUND AND PURPOSE: Calu-3 cells are derived from serous cells of human lung submucosal glands, a prime target for therapy in cystic fibrosis (CF). Calu-3 cells can be cultured to form epithelia capable of transepithelial transport of chloride. A CF Calu-3 cell is not available. EXPERIMENTAL APPROACH: A retroviral vector was used to cause persistent down regulation of CFTR using siRNA methodology, in Calu-3 cells. A Calu-3 cell line with CFTR content less than 5% of the original line has been established. Epithelia grown using the modified cells have been used in comparative studies of transporting capability. KEY RESULTS: All aspects of cAMP activated chloride secretion were attenuated in the epithelia with reduced CFTR content. However transporting capability was reduced less than the CFTR content. From studies with the CFTR channel inhibitor, GlyH 101, it was concluded that wild type Calu-3 cells have a reserve of CFTR channels not located in the membrane, but available for replacement, while in the modified Calu-3 cell line there was little or no reserve. Lubiprostone, a putative ClC-2 activator, increased transepithelial chloride secretion in both modified and wild type Calu-3 epithelia. Modified Calu-3 epithelia with the residual CFTR currents blocked with GlyH-101 responded equally well to lubiprostone as those without the blocking agent. CONCLUSIONS AND IMPLICATIONS: It appears that lubiprostone is capable of stimulating a non-CFTR dependent transepithelial chloride secretion in Calu-3 monolayers, with obvious implications for CF therapy. Cell lines, however, do not always reflect the behaviour of the native tissue with integrity. PMID- 17339839 TI - Regulation of the expression of soluble guanylyl cyclase by reactive oxygen species. AB - BACKGROUND AND PURPOSE: Superoxide anions produced during vascular disease scavenge nitric oxide (NO), thereby reducing its biological activity. The aim of the present study was to investigate whether reactive oxygen species (ROS) have a direct effect on soluble guanylyl cyclase (sGC) subunit levels and function and to ascertain the mechanism(s) involved. EXPERIMENTAL APPROACH: Rat aortic smooth muscle cells (RASM) or freshly isolated vessels were exposed to reactive oxygen species (ROS)-generating agents and sGC subunit expression was determined at the mRNA and/or protein level. cGMP accumulation was also determined in RASM exposed to ROS. KEY RESULTS: Incubation of smooth muscle cells with H(2)O(2), xanthine/xanthine oxidase (X/XO) or menadione sodium bisulphite (MSB) significantly decreased protein levels of alpha1 and beta1 subunits of sGC and reduced SNP-induced cGMP formation. Similarly, sGC expression was reduced in freshly isolated vessels exposed to ROS-generating agents. The ROS-triggered inhibition of alpha1 and beta1 levels was not blocked by proteasome inhibitors, suggesting that decreased sGC protein was not due to protein degradation through this pathway. Real time RT-PCR analysis demonstrated a 68% reduction in steady state mRNA levels for the alpha1 subunit following exposure to H(2)O(2). In addition, alpha1 promoter-driven luciferase activity in RASM decreased by 60% after H(2)O(2) treatment. CONCLUSION AND IMPLICATIONS: We conclude that oxidative stress triggers a decrease in sGC expression and activity that results from reduced sGC steady state mRNA levels. Altered sGC expression is expected to contribute to the changes in vascular tone and remodeling observed in diseases associated with ROS overproduction. PMID- 17339841 TI - Methylamine-dependent release of nitric oxide and dopamine in the CNS modulates food intake in fasting rats. AB - BACKGROUND AND PURPOSE: Methylamine is an endogenous aliphatic amine exhibiting anorexigenic properties in mice. The aim of this work was to show whether methylamine also modifies feeding behaviour in rats and, if so, to identify the mediator(s) responsible for such effects. EXPERIMENTAL APPROACH: Microdialysis experiments with the probe inserted in the periventricular hypothalamic nucleus were carried out in 12 h starved, freely moving rats. Collected perfusate samples following methylamine injection (i.c.v.) were analysed for nitric oxide by chemiluminescence and for dopamine and 5-hydroxytryptamine content by HPLC. Kv1.6 potassium channel expression was reduced by antisense strategy and this decrease quantified by semi-quantitative RT-PCR analysis. KEY RESULTS: Methylamine showed biphasic dose-related effects on rat feeding. At doses of 15-30 microg per rat, it was hyperphagic whereas higher doses (60-80 microg) were hypophagic. Methylamine stimulated central nitric oxide (+115% vs. basal) following hyperphagic and dopamine release (60% over basal values) at hypophagic doses, respectively. Treatment with L-N(G)-nitro-L-arginine-methyl ester (i.c.v. 2 microg 10 microl(-1)) or with alpha-methyl-p-tyrosine (i.p. 100 mg kg(-1)) before methylamine injection, reduced nitric oxide output and hyperphagia, or dopamine release and hypophagia respectively. Moreover, hypophagia and hyperphagia, as well as nitric oxide and dopamine release were significantly reduced by down regulating brain Kv1.6 potassium channel expression. CONCLUSIONS AND IMPLICATIONS: The effects of methylamine on feeding depend on the hypothalamic release of nitric oxide and dopamine as a result of interaction at the Kv1.6 channels. The study of methylamine levels in the CNS may provide new perspectives on the physiopathology of alimentary behaviour. PMID- 17339842 TI - Activation of 5-HT1B and 5-HT1D receptors in the rat nucleus tractus solitarius: opposing action on neurones that receive an excitatory vagal C-fibre afferent input. AB - BACKGROUND AND PURPOSE: Central 5-HT-containing pathways are known to be important in cardiovascular regulation and a crucial area for this regulation is the nucleus tractus solitarius (NTS), which contains many of the known 5-HT receptor subtypes. In this study the role of 5-HT(1B) and 5-HT(1D) receptors, targets for the antimigraine drugs known collectively as triptans, was examined in the NTS. EXPERIMENT APPROACH: Extracellular recordings were made, in anaesthetized rats, from 109 NTS neurones that were excited by electrical stimulation of the vagus and drugs were applied ionophoretically to these neurones. KEY RESULTS: The 5-HT(1B/1D) receptor agonist sumatriptan applied to 64 neurones produced a 64% reduction in the firing rate of 54 of these neurones. Ketanserin, a 5-HT(1D/2A) receptor antagonist, alone had little effect, but co applied with sumatriptan significantly attenuated this inhibition, whilst co application of the 5-HT(1B) receptor antagonist GR55562 resulted in potentiation of this inhibition. Sumatriptan also caused a 25% reduction in vagal afferent evoked activity as well as that caused by stimulation of cardiopulmonary afferents. In another 41 neurones the 5-HT(1B) receptor agonist CP-93 129 produced a doubling of the background firing rate in 31 of these neurones and a significant increase in both vagal afferent evoked activity and that evoked by cardiopulmonary afferent activation. CONCLUSIONS AND IMPLICATIONS: Activation of 5-HT(1B) and 5-HT(1D) receptors have opposing actions on NTS neurones of excitation and inhibition, respectively. As both receptors are negatively coupled to adenylate cyclase this would indicate that they have different anatomical locations within NTS. PMID- 17339844 TI - Erythropoietin involves the phosphatidylinositol 3-kinase pathway, 14-3-3 protein and FOXO3a nuclear trafficking to preserve endothelial cell integrity. AB - BACKGROUND AND PURPOSE: Clinical indications for erythropoietin (EPO) in the vascular system reach far beyond the treatment of anemia, but the development of EPO as a non-toxic agent rests heavily upon the cellular pathways controlled by EPO that require elucidation. EXPERIMENTAL APPROACH: We modulated gene activity and examined cellular trafficking of critical pathways during oxidative stress that may work in concert with EPO to protect primary cerebral endothelial cells (ECs) during oxidative stress, namely protein kinase B (Akt1), 14-3-3 protein, the Forkhead transcription factor FOXO3a. KEY RESULTS: Here, we show that preservation of ECs by EPO during oxygen-glucose deprivation (OGD) required the initial activation of the phosphatidylinositol 3-kinase (PI-3K) pathway through Akt1, since specific pharmacological blockade of Akt1 activity or gene silencing of Akt1 prevented EC protection by EPO. EPO subsequently involved a series of anti-apoptotic pathways to activate STAT3, STAT5, and ERK 1/2. Furthermore, EPO maintained the inhibitory phosphorylation and integrity of the 'pro-apoptotic' transcription factor FOXO3a, promoted the binding of FOXO3a to 14-3-3 protein and regulated the intracellular trafficking of FOXO3a. Additionally, gene silencing of FOXO3a during OGD significantly increased EC survival, but did not synergistically improve cytoprotection by EPO, illustrating that EPO relied upon the blockade of the FOXO3a pathway. CONCLUSIONS AND IMPLICATIONS: Our work defines a novel cytoprotective pathway in ECs that involves PI-3 K, STAT3, STAT5, ERK 1/2, 14-3-3 protein and FOXO3a, which can be targeted for the development of EPO as a clinically effective and safe agent in the vascular system. PMID- 17339845 TI - Cytokine upregulation of proteinase-activated-receptors 2 and 4 expression mediated by p38 MAP kinase and inhibitory kappa B kinase beta in human endothelial cells. AB - BACKGROUND AND PURPOSE: Up-regulation of proteinase-activated receptor-2 (PAR2) is a factor in a number of disease states and we have therefore examined the signalling pathways involved in the expression of the receptor. EXPERIMENTAL APPROACH: We investigated the effects of tumour necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta), trypsin and the PAR2 activating peptide, 2 furoyl(2f)-LIGKV-OH on both mRNA and functional expression of PAR2 in human umbilical vein endothelial cells (HUVECs). The effect of specific chemical inhibitors and dominant negative adenovirus constructs of the mitogen-activated protein kinase (MAPK) cascade and the nuclear factor kappa B (NF-kappaB) signalling pathway was assessed. Methods included semi-quantitative and quantitative RT-PCR, [(3)H]inositol phosphate (IP) accumulation and Ca(2+) dependent fluorescence. KEY RESULTS: The above agonists induced both mRNA and functional expression of PAR2; PAR4 mRNA, but not that for PAR1 or PAR-3, also increased following TNFalpha treatment. Inhibition of p38 MAP kinase reduced PAR2 and PAR4 expression, whilst inhibition of MEK1/ERK/JNK was without effect. A similar dependency upon p38 MAP kinase was observed for the expression of PAR4. TNFalpha -induced enhancement of PAR2 stimulated [(3)H]-inositol phosphate accumulation (IP) and Ca(2+) signalling was abolished following SB203580 pre treatment. Infection with adenovirus encoding dominant-negative IKKbeta (Ad.IKKbeta(+/-)) and to a lesser extent dominant-negative IKKalpha (Ad.IKKalpha(+/-)), substantially reduced both control and IL-1beta- induced expression of both PAR2 and PAR4 mRNA and enhancement of PAR2-stimulated IP accumulation and Ca(2+) mobilisation. CONCLUSIONS AND IMPLICATIONS: These data reveal for the first time the signalling events involved in the upregulation of both PAR2 and PAR4 during pro-inflammatory challenge. PMID- 17339846 TI - Single-molecule analysis of DNA-protein complexes using nanopores. AB - We present a method for rapid measurement of DNA-protein interactions using voltage-driven threading of single DNA molecules through a protein nanopore. Electrical force applied to individual ssDNA-exonuclease I complexes pulls the two molecules apart, while ion current probes the dissociation rate of the complex. Nanopore force spectroscopy (NFS) reveals energy barriers affecting complex dissociation. This method can be applied to other nucleic acid-protein complexes, using protein or solid-state nanopore devices. PMID- 17339843 TI - Inflammation as a causative factor in the aetiology of Parkinson's disease. AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting mainly the elderly, although a small proportion of PD patients develop the illness at a much younger age. In the former group, idiopathic PD patients, the causes of the illness have been the subject of longstanding debate with environmental toxins, mitochondrial dysfunction, abnormal protein handling and oxidative stress being suggested. One problem has been that the epidemiology of PD has offered few clues to provide evidence for a single major causative factor. Comparatively recently it has been found that in both patients and experimental models of PD in animals neuroinflammation appears to be a ubiquitous finding. These cases present with all of the classical features of inflammation including phagocyte activation, increased synthesis and release of proinflammatory cytokines and complement activation. Although this process is vital for normal function and protection in both the CNS, as in the periphery, it is postulated that in the aetiology of PD this process may spiral out of control with over activation of microglia, over production of cytokines and other proinflammatory mediators as well as the release of destructive molecules such as reactive oxygen species. Given that dopaminergic neurons in the substantia nigra are relatively vulnerable to 'stress' and the region has a large population of microglia in comparison to other CNS structures, these events may easily trigger neurodegeneration. These factors are examined in this review along with a consideration of the possible use of anti-inflammatory drugs in PD. PMID- 17339847 TI - High-resolution three-dimensional imaging of large specimens with light sheet based microscopy. AB - We report that single (or selective) plane illumination microscopy (SPIM), combined with a new deconvolution algorithm, provides a three-dimensional spatial resolution exceeding that of confocal fluorescence microscopy in large samples. We demonstrate this by imaging large living multicellular specimens obtained in a three-dimensional cell culture. The ability to rapidly image large samples at high resolution with minimal photodamage provides new opportunities especially for the study of subcellular processes in large living specimens. PMID- 17339848 TI - Balancing drug availability and patient safety. PMID- 17339849 TI - Leptin and colorectal cancer: an undefined link. PMID- 17339850 TI - Is double balloon enteroscopy the best initial imaging method for obscure gastrointestinal bleeding? PMID- 17339851 TI - Complications of antiobesity surgery. AB - Bariatric surgery is an effective long-term treatment for patients who suffer from morbid obesity, the incidence of which is increasing in North America. Laparoscopic gastric bypass and laparoscopic adjustable gastric band placement are the two commonly performed bariatric procedures. This article discusses the indications for bariatric surgery and the early and late complications associated with these two procedures. Laparoscopic biliopancreatic diversion and laparoscopic sleeve gastrectomy are also briefly discussed. PMID- 17339852 TI - Technology insight: applications of MRI for the evaluation of benign disease of the pancreas. AB - This article reviews the role of MRI in the evaluation of benign pancreatic disease. Although MRI and magnetic resonance cholangiopancreatography (MRCP) are most often used to evaluate the liver and bile duct, technical advances such as the use of secretin stimulation also allow for high-quality imaging of the pancreas and pancreatic ductal system. Secretin-stimulated MRCP (S-MRCP) can aid the diagnosis of acute and chronic pancreatitis, and delineate ductal pathology such as benign strictures and duct leaks. There seems to be a role for S-MRCP in the assessment of pancreatic function and (possibly) sphincter of Oddi dysfunction. When endoscopic or surgical therapy is planned, S-MRCP can help to establish a diagnosis as well as offer a 'road map' to guide therapy. S-MRCP is noninvasive and almost entirely without risk to the patient, which gives it a distinct advantage over traditional endoscopic methods of diagnosis for conditions such as pancreas divisum and other ductal pathology. The information provided by S-MRCP, obtained before endoscopic or surgical therapy is attempted, can assist the patient and physician in making a fully informed decision with regard to the risks and probable benefits of any planned intervention. PMID- 17339853 TI - Drug insight: aminosalicylates for the treatment of IBD. AB - Sulfasalazine and mesalazine (also known as mesalamine; 5-aminosalicylic acid) preparations have for many years been used for the treatment of IBD (i.e. ulcerative colitis and Crohn's disease), for both active disease and the control of remission. It has also been suggested that mesalazine is a chemoprophylactic agent that protects against the development of colorectal cancer. This Review focuses on the latest clinical evidence for the use of these aminosalicylates for the treatment of IBD, and concludes that sulfasalazine and mesalazine are useful for the treatment of both active and quiescent ulcerative colitis, whereas they have no clinical effect on either active or inactive Crohn's disease. Furthermore, evidence is lacking that mesalazine per se is a chemoprophylactic agent. PMID- 17339854 TI - Primary malignant melanoma of the esophagus with multiple esophageal lesions. AB - BACKGROUND: A 48-year-old Chinese woman presented with a 2-month history of progressive dysphagia for solids, and (less frequently) liquids. She had minimal weight loss and no family history of cancer. INVESTIGATIONS: Physical examination, conventional esophagogastroduodenoscopy, CT, fluorodeoxyglucose-PET, endoscopic ultrasonography, and histopathologic examination of excised tumor and biopsy specimens. DIAGNOSIS: Primary malignant esophageal melanoma with submucosal infiltration but no distant metastasis. MANAGEMENT: Endoscopic polypectomy followed by near-total esophagectomy with esophagogastric anastomosis. PMID- 17339856 TI - The art and science of personalized medicine. PMID- 17339859 TI - Personalized medicine: building the GPS to take us there. PMID- 17339860 TI - Enhancing race-based prescribing precision with pharmacogenomics. AB - In the world of medicine and therapeutics, race and ethnicity might reasonably be considered as biomarkers or predictors of drug effect. Recognizing that all biomarkers are imperfect, self-reported race can be viewed as a complex combination of genetic and nongenetic biomarkers that is used by prescribing physicians as a predictor of drug effect. The use of pharmacogenetic markers, such as haplotypes, patterns of candidate genes, and specific genotypes, may be used to enhance the precision of race-based prescribing and, when possible, should be combined with nongenetic predictors of responses to optimize the individualization of therapy. PMID- 17339862 TI - Acute effects of sibutramine administration on the autonomic nervous system in obese subjects. PMID- 17339864 TI - Influence of ethanol and gender on methylphenidate pharmacokinetics and pharmacodynamics. AB - This study explores the hypotheses that: (1) ethanol will interact with dl Methylphenidate (MPH) to enantioselectively elevate plasma d-MPH, and primarily yield l-ethylphenidate as a transesterification metabolite; (2) women will exhibit lower relative bioavailability of MPH than men; and (3) sex-dependent differences in subjective effects will exist. dl-MPH HCl (0.3 mg/kg) was administered orally 30 min before ethanol, 30 min after ethanol (0.6 gm/kg), or without ethanol, in a randomized, normal subject three-way crossover study of 10 men and 10 women. Pharmacokinetic parameters were compared. Subjective effects were recorded using visual analog scales. One subject was a novel poor MPH metabolizer whose data were analyzed separately. Ethanol after or before MPH significantly (P<0.0001) elevated the geometric mean for the maximum d-MPH plasma concentration (C(max) (+/-SD)) from 15.3 (3.37) ng/ml to 21.5 (6.81) and 21.4 (4.86), respectively, and raised the corresponding geometric mean for the area under the concentration-time curve values from 82.9 (21.7) ng ml/h to 105.2 (23.5) and 102.9 (19.2). l-MPH was present in plasma only at 1-3% of the concentration of d-MPH, except in the poor metabolizer where l-MPH exceeded that of d-MPH. The metabolite l-ethylphenidate frequently exceeded 1 ng/ml in plasma, whereas d-ethylphenidate was detected only in low pg/ml concentrations. Women reported a significantly greater stimulant effect than men when questioned "Do you feel any drug effect?" (P<0.05), in spite of lower mean plasma d-MPH area under the response-time curves in women. Ethanol elevates plasma d-MPH C(max) and area under the concentration-time curve by approximately 40% and 25%, respectively. If the poor metabolizer of MPH proves to be a distinct phenotype, determining the genetic mechanism may be of value for individualizing drug therapy. The more pronounced stimulant effects experienced by women have sex based abuse liability implications. PMID- 17339865 TI - Gene modulatory effects, pharmacokinetics, and clinical tolerance of interferon alpha1b: a second member of the interferon-alpha family. AB - Interferon-alpha1 (IFN-alpha1), which may have a primary role in innate immunity, differs significantly in amino-acid sequence from IFN-alpha2, the only recombinant IFN-alpha with substantial clinical evaluation. Patients with metastatic malignancies received daily subcutaneous doses of 1.5-270 mug/m(2) of recombinant IFN-alpha1b. Gene modulation, pharmacokinetics, tolerability, and disease response were determined. Significant (P<0.01) dose and gene-dependent increases of 2-10 fold occurred in IFN-stimulated genes, including four (tumor necrosis factor-related apoptosis-inducing ligand, cig 5, p56, GEM) never previously identified as increased in patients; significant increases (P<0.01) resulted at the lowest dose (1.5 microg/m(2); 1.5 x 10(4) human antiviral units/m(2)). Increases (P<0.01) were sustainable for >4 weeks. Peak levels of IFN alpha1b were at 3 h; an increase of approximately eightfold in both C(max) and AUC occurred between 15 microg/m(2) and 270 microg/m(2). Chronic toxicities of anorexia, weight loss, and fatigue were relatively uncommon. Eighteen patients were treated for >8 weeks; none experienced >grade 1 weight loss. Three patients at the highest dose developed grade 3 fatigue after > or =3 months, which required dose reduction or discontinuation. Patient acceptability of fatigue defined a dose for initiation of Phase II trials, 270 microg/m(2). Six patients (five with renal cell carcinoma) had progression-free survival for >1 year, including two who had partial responses. IFN-alpha1b resulted in potent stimulation of IFN-regulated genes and tumor regressions in renal cell carcinoma. Unique gene modulatory effects, when coupled with the moderate severity of side effects and a potentially central role in innate immunity, provide rationale for further clinical evaluation of IFN-alpha1 in virus infections and cancer. PMID- 17339863 TI - The pharmacogenetics research network: from SNP discovery to clinical drug response. AB - The NIH Pharmacogenetics Research Network (PGRN) is a collaborative group of investigators with a wide range of research interests, but all attempting to correlate drug response with genetic variation. Several research groups concentrate on drugs used to treat specific medical disorders (asthma, depression, cardiovascular disease, addiction of nicotine, and cancer), whereas others are focused on specific groups of proteins that interact with drugs (membrane transporters and phase II drug-metabolizing enzymes). The diverse scientific information is stored and annotated in a publicly accessible knowledge base, the Pharmacogenetics and Pharmacogenomics Knowledge base (PharmGKB). This report highlights selected achievements and scientific approaches as well as hypotheses about future directions of each of the groups within the PGRN. Seven major topics are included: informatics (PharmGKB), cardiovascular, pulmonary, addiction, cancer, transport, and metabolism. PMID- 17339866 TI - Effects of supportive treatment such as antioxidant or leukotriene receptor antagonist drugs on inflammatory and respiratory parameters in asthma patients. AB - In this study, prospectively, we aimed to determine the effects of the different treatment alternatives on the oxidant system and inflammatory and clinic determinants during the stable period of 1 month following an asthmatic attack. Thirty-one patients (22 female, nine male) were randomly divided into three groups following the stabilization of an acute asthma attack. The control group that is an additional group to the three patient groups consisted of 10 healthy volunteers (five female, five male). The following protocols were used for 4 weeks: Group I: short-acting inhaler beta2 mimetic as required (treatment A)+800 mug inhaler budesonide (treatment B)+leukotriene receptor antagonist; Group II: treatment A and B; Group III: treatment A and B+vitamin E. The serum levels before and after treatment of eosinophilic cationic protein (ECP), leukotriene E4 (LTE(4)), and malondialdehyde (MDA) were determined. The values before and after treatment were statistically compared both with each other and control values. Pretreatment ECP, LTE(4), and MDA levels for the three groups were significantly higher compared with post-treatment levels (P<0.05 to P<0.001) and the control levels (P<0.01 to P<0.001). However, when post-treatment levels were compared with those of the control group, no significant differences were found (P>0.05). Lack of significant variation was observed when the pre- and post-treatment differences in the three groups were compared for each one of ECP, LTE(4), and MDA levels (P>0.05). Leukotriene receptor antagonist or antioxidant agents added to standard asthma treatment did not make a significant contribution on ECP, LTE(4), and MDA levels and respiratory parameters such as spirometric function tests. Etiologic factors and/or the possible changes in different pathogenetic ways of the inflammation process may have been responsible for nonsignificant intertreatment difference in the biomarker levels. The result confirms that suppressing the inflammation in asthma enables the entire inflammatory pathologic process to be controlled. PMID- 17339867 TI - Thorough QT study with recommended and supratherapeutic doses of tolterodine. AB - The objective of our study was to determine the QTc effects of tolterodine. A crossover-design thorough QT study of recommended (2 mg twice daily) and supratherapeutic (4 mg twice daily) doses of tolterodine, moxifloxacin (400 mg once daily), and placebo was performed. Electrocardiograms (ECGs) and pharmacokinetic samples were obtained on days 1-4; time-matched baseline ECGs were taken on day 0. Mean placebo-subtracted change from baseline Fridericia corrected QT (QTcF) during peak drug exposure on day 4 was the primary end point. Mean QTcF prolongation of moxifloxacin was 8.9 ms (machine-read) and 19.3 ms (manual-read). At recommended and supratherapeutic tolterodine doses, mean QTcF prolongation was 1.2 and 5.6 ms (machine-read), respectively, and 5.0 and 11.8 ms (manual-read), respectively. The QTc effect of tolterodine was lower than moxifloxacin. No subject receiving tolterodine exceeded the clinically relevant thresholds of 500 ms absolute QTc or 60 ms change from baseline. In conclusion, tolterodine does not have a clinically significant effect on QT interval. PMID- 17339868 TI - Association of CYP3A5 polymorphisms with hypertension and antihypertensive response to verapamil. AB - In the CYP3A5 gene, the A>G (*3) and G>A (*6) polymorphisms result in severely decreased expression of CYP3A5 enzyme relative to a normal functional allele (*1). We sought to determine if the CYP3A5 genetic polymorphisms were associated with level of blood pressure (BP), risk of hypertension (HTN), and the antihypertensive response to verapamil. A total of 676 normotensive and hypertensive participants (mean age 49+/-8.2 years) from the Hypertension Genes study and 722 patients (mean age 66+/-9 years) from the International Verapamil/Trandolapril Study Genetic Substudy (INVEST-GENES) were genotyped for CYP3A5 to test for associations with BP, HTN, and in the latter cohort, antihypertensive response to verapamil. CYP3A5 haplotypes were determined using PHASE 2, with any allele containing either (*3) or (*6) designated as non functional. In the HTN genes population, there were no significant differences based on the number of functional CYP3A5 alleles, in systolic blood pressure (SBP) or diastolic blood pressure (DBP) among the normotensive whites or blacks (all P> or =0.70) or in allele frequency between normotensives and hypertensives. In INVEST-GENES, when controlled for baseline BP, race, age, and gender, untreated BP in carriers versus non carriers of a CYP3A5 functional allele was 158.2+/-13.7 and 154.8+/-13.7 (P=0.061), respectively. CYP3A5 functional allele status was marginally associated with the SBP response to verapamil in blacks (P=0.075) and Hispanics (P=0.056), but not in whites (P=0.40), with the effect being largely driven by higher SBP in the carriers of two functional alleles. There was no association with DBP response and CYP3A5 allele status. CYP3A5 genotype does not contribute importantly to BP or risk of HTN, but may influence response to calcium channel blockers in populations in which carrier status of two functional alleles is common. PMID- 17339869 TI - The impact of UGT1A8, UGT1A9, and UGT2B7 genetic polymorphisms on the pharmacokinetic profile of mycophenolic acid after a single oral dose in healthy volunteers. AB - We studied whether polymorphisms in the UGT1A8, UGT1A9, and UGT2B7 genes, the enzymes producing the phenolic (MPAG) and acyl (AcMPAG) glucuronides of mycophenolic acid (MPA), could contribute to the interindividual variation observed in mycophenolate mofetil (MMF) pharmacokinetics (PKs). This study enrolled 17 healthy volunteers with no polymorphisms (controls) and 17 carriers of UGT1A9 -275/-2152 selected among 305 individuals genetically screened for UDP glucuronosyltransferase (UGT) polymorphisms. Additional investigative groups included carriers of UGT1A8*2 (A173G) (n=9), UGT1A8*3 (C277Y) (n=4), and UGT1A9*3 (M33T) (n=5). Genetic analysis also included UGT2B7 to detect UGT2B7*2 (His268Tyr) and the promoter haplotype -1248A>G, -1241T>C, -1054T>C, -842G>A, 268A>G, -102T>C. Kinetics were measured in plasma and urine after a single 1.5 g oral dose of MMF, by high-performance liquid chromatography coupled with tandem mass spectrometry, over 12 h after drug intake. Compared to controls, MPA exposure was significantly lower for UGT1A9 -275/-2152 carriers, with no significant changes in MPAG. The estimates of enterohepatic (re)cycling (area under the concentration-time curve (AUC6-12 h/AUC0-12 h)) were significantly lower for MPA, MPAG, and AcMPAG in UGT1A9 -275/-2152 subjects. Compared with controls, UGT1A9*3 carriers had higher MPA and AcMPAG exposure, whereas homozygosity for the UGT1A8*2 allele and heterozygosity for UGT1A8*3 allele had no impact on MPA PKs. Compared with UGT2B7*1/*1 individuals (n=10), UGT2B7*2/*2 subjects (n=17) presented significantly higher free MPA C(max) values and elevated free and total MPA. Results indicate that after a single oral dose of MMF in healthy volunteers, specific UGT genotypes significantly alter MPA PKs and this clearly warrants additional studies with complete and detailed genetic profiling of UGT1A8, UGT1A9, and UGT2B7 genes. PMID- 17339870 TI - Safety and pharmacokinetics of paracetamol following intravenous administration of 5 g during the first 24 h with a 2-g starting dose. AB - Intravenous (i.v.) paracetamol is used as 1-g infusions with a maximal daily dose of 4 g/day. However, a higher initial analgesic dose could be of interest in the immediate postoperative period when the pain is maximal. The purpose of the present study was to determine in healthy subjects the safety and the pharmacokinetics of i.v. paracetamol, starting with a 2-g dose, followed by 1-g doses every 6 h, leading to a total of 5 g the first 24 h. This was an open label, single-sequence study. The paracetamol pharmacokinetic profile was assessed in 26 subjects after both the 2-g starting dose and the 1-g doses. Safety, especially hepatotoxicity, was evaluated up to 72 h after the initial 2-g dose. Following the first 15-min i.v. administration of paracetamol 2 g, plasma concentrations ranged from 67.9+/-21.8 mug/ml (peak plasma concentration (C(max)) at the end of infusion) to 6.2+/-2.3 mug/ml (trough plasma concentration (C(min)) measured just before the next infusion) without any C(max) in the toxic range for any subject. After the repeated 1-g infusions, the plasma concentrations were approximately 35% lower than that measured after 2 g, showing the absence of accumulation. No clinical adverse events related to the drug administration nor clinically relevant changes in laboratory parameters, including biochemical signs of hepatotoxicity, were reported. After i.v. administration of paracetamol 2-g starting dose and 5 g during the first 24 h, the pharmacokinetics of paracetamol remain unchanged, with concentrations far below the toxic threshold. Overall, these results demonstrate that the i.v. administration of a 2-g starting dose of paracetamol, followed by three i.v. administrations of 1 g during the first 24 h is safe in healthy subjects. PMID- 17339871 TI - Molecular imaging as a tool for personalized and targeted anticancer therapy. PMID- 17339872 TI - Should pharmacogenomic studies be required for new drug approval? AB - The field of pharmacogenetics has existed since the 1950s, when it was demonstrated that some drug effects could differ substantially among race and ethnic groups, and that some drug metabolizing enzyme activities were inherited. During the 1990s, application of molecular biology to the study of inherited drug related phenotypes proved the genetic basis of several genetic polymorphisms. Genomic technology has now demonstrated that germline genetic variability among humans is extremely common. The combined weight of proven examples whereby pharmacogenetics affects drugs, and the possibility of even more examples being elucidated in the coming decades, dictates that pharmacogenetics be incorporated into the drug approval process. It is our contention that minimal pharmacogenetic testing should be required for all new drug applications to the Food and Drug Administration (FDA). This would include a requirement for germline DNA to be prospectively collected from all subjects participating in preapproval clinical trials. For drugs that are metabolized by enzymes whose genes have clearly inactivating polymorphisms, clinical trial participants should be genotyped for those polymorphisms. PMID- 17339873 TI - Pharmacogenetics of opioids. AB - Opioids are used for acute and chronic pain and dependency. They have a narrow therapeutic index and large interpatient variability in response. Genetic factors regulating their pharmacokinetics (metabolizing enzymes, transporters) and pharmacodynamics (receptors and signal transduction elements) are contributors to such variability. The polymorphic CYP2D6 regulates the O-demethylation of codeine and other weak opioids to more potent metabolites with poor metabolizers having reduced antinociception in some cases. Some opioids are P-glycoprotein substrates, whereas, ABCB1 genotypes inconsistently influence opioid pharmacodynamics and dosage requirements. Single-nucleotide polymorphisms in the mu opioid receptor gene are associated with increasing morphine, but not methadone dosage requirements and altered efficacy of mu opioid agonists and antagonists. As knowledge regarding the interplay between genes affecting opioid pharmacokinetics including cerebral kinetics and pharmacodynamics increases, our understanding of the role of pharmacogenomics in mediating interpatient variability in efficacy and side effects to this important class of drugs will be better informed. Opioid drugs as a group have withstood the test of time in their ability to attenuate acute and chronic pain. Since the isolation of morphine in the early 1800s by Friedrich Serturner, a large number of opioid drugs beginning with modification of the 4,5-epoxymorphinan ring structure were developed in order to improve their therapeutic margin, including reducing dependence and tolerance, ultimately without success. PMID- 17339874 TI - Planning for a national effort to enable and accelerate discoveries in pharmacogenetics: the NIH Pharmacogenetics Research Network. AB - The Pharmacogenetics Research Network (PGRN) was conceived as a broad network based approach to research studies in pharmacogenetics and pharmacogenomics, with the central feature of a database that would be hypothesis-generating and open to all scientific investigators. The original working group emphasized the importance of carefully relating phenotypes for drug responses to genotypes, and understanding the relationships functionally and mechanistically. The mission of the PGRN is to advance our knowledge of the genetic basis for variable drug responses. The ultimate goal of the effort is to determine clinically significant sequence variations in order to predict the right choice and dose of medications for individuals and to prepare for implementation of this information to improve health care. PMID- 17339875 TI - More evidence supports the association of PPP3CC with schizophrenia. AB - Calcineurin is a calcium/calmodulin-dependent protein phosphatase composed of two subunits, a regulatory subunit of calcineurin B (CNB) and a catalytic subunit of calcineurin A (CNA). PPP3CC is the gamma isoform of CNA located at the chromosome 8p21.3 region. To evaluate the association between PPP3CC and schizophrenia in the Taiwanese population, 10 single nucleotide polymorphism (SNP) markers across the gene were genotyped by the method of MALDI-TOF in 218 schizophrenia families with at least two affected siblings. One SNP (rs2272080) located around the exon 1 untranslated region was nominally associated with schizophrenia (P=0.024) and significantly associated with the expression of PPP3CC in lymphoblast cell line; the TT and TG genotype had significantly higher relative expression levels than the GG genotype (P=0.0012 and 0.015, respectively). In further endophenotype stratification, the single locus of rs2272080 and the haplotypes of both two-SNP haplotype (rs7833266-rs2272080) and seven-SNP haplotype (rs2461491-rs2469758 rs2461489-rs2469770-rs2449340-rs1482337-rs2252471) showed significant associations with the subgroup of schizophrenia with deficits of the sustained attention as tested by the continuous performance test (CPT, P<0.05) and the executive functioning as tested by the Wisconsin Card Sorting Test (WCST, P<0.05). The results suggest that PPP3CC gene may be a true susceptibility gene for schizophrenia. PMID- 17339876 TI - Validation of amyloid-beta peptides in CSF diagnosis of neurodegenerative dementias. AB - Biomarkers for differential diagnosis of the three most frequent degenerative forms of dementia, Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementias (FTD), are currently under intensive investigation, but disease-specific biomarkers for FTD and DLB are still lacking. We analyzed 303 cerebrospinal fluid (CSF) samples of 71 AD, 32 DLB and 36 FTD patients in comparison to 93 various other dementias (OD), 20 peripheral neurologic disease (PND) controls, 25 neurodegenerative disorders without dementia (ND) and 26 depressive cognitive complainers (DCC) for distinct CSF amyloid-beta (Abeta) peptide patterns, using the quantitative Abeta-SDS-PAGE/immunoblot. Additionally, the novel electrochemiluminescence technique (MSD) was used to validate the measures on Abeta1-38. The main outcome measures were a striking decrease of Abeta1-42 in AD (P=7.4 x 10(-19)), and most interestingly a pronounced decrease of Abeta1-38 in FTD (P=9.6 x 10(-7)). Moreover, a novel peptide that most probably represents an oxidized alpha-helical form of Abeta1-40 (Abeta1-40(ox)) displayed a highly significant increase in DLB (P=3.7 x 10(-3)) as compared to non-demented disease controls. The overall diagnostic accuracy of percentage Abeta peptide abundances (Abeta1-X%) was clearly superior to absolute CSF Abeta levels. Abeta1-42% and Abeta1-38% enabled contrasts of 85% or beyond to distinguish AD and FTD, respectively, from all other investigated subjects. Abeta1-40(ox)% yielded a diagnostic sensitivity and specificity of 88 and 73% for the detection of DLB among all other investigated patients. We found a strong correlation between Abeta1-38 levels as measured by the Abeta-SDS-PAGE/immunoblot and MSD, respectively. CSF Abeta peptides may reflect disease-specific impact of distinct neurodegenerative processes on Abeta peptide metabolism and represent a potential diagnostic biomarker for AD, FTD and DLB. PMID- 17339877 TI - Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study. AB - Genetic risk factors for ticlopidine-induced hepatotoxicity were determined in 22 Japanese patients with ticlopidine-induced hepatotoxicity and 85 Japanese patients who tolerated ticlopidine therapy without experiencing adverse reactions. There was a significant correlation between ticlopidine-induced hepatotoxicity and five human leukocyte antigen (HLA) alleles: HLA-A*3303, HLA B*4403, HLA-Cw*1403, HLA-DRB1*1302 and HLA-DQB1*0604 (corrected probability (P) value (Pc)<0.01). In particular HLA-A*3303 was present in 15 (68%) of the 22 patients with ticlopidine-induced hepatotoxicity and in 12 (14%) of the 85 ticlopidine-tolerant patients (odds ratio, 13.04; 95% confidence interval (CI), 4.40-38.59; the corrected P-value (Pc)=1.24 x 10(-5)). HLA-A*3303 was present in 12 (86%) of the 14 patients with ticlopidine-induced cholestatic hepatotoxicity (odds ratio, 36.50; 95% CI, 7.25-183.82, Pc=7.32 x 10(-7)). Ticlopidine-induced severe cholestatic hepatotoxicity occurred more frequently in subjects with HLA A*3303 and its haplotype in Japanese patients. These findings may explain the high incidence of ticlopidine-induced hepatotoxicity in Japanese patients mediated via an immune-mediated mechanism. PMID- 17339878 TI - Prostatic volume and volume-adjusted prostate-specific antigen as predictive parameters for prostate cancer patients with intermediate PSA levels. AB - The object of the study was to examine the usefulness of volume-adjusted prostate specific antigen (PSA) parameters for prediction of prostate cancer in the patients with intermediate PSA levels. The subjects were 235 patients with intermediate PSA levels (range: 4.1-10.0 ng/ml) whose prostate volume (PV) and prostate transition zone volume (TZV) were evaluated between August 1996 and April 2004. PSA, PV, TZV, PSA density (PSAD) (PSA/PV) and PSA transition zone density (PSATZD) (PSA/TZV) were assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Simple and multivariate logistic regression analyses were used to analyze the odds ratios of age, PSA, PSAD, PSATZD, PV, TZV, digital rectal examination (DRE) and transrectal ultrasonography (TRUS) findings. Fifty-five patients (23.4%) of 235 patients had biopsy-proven prostate cancer. The univariate analysis revealed significant differences in the mean values of age, PSAD, PSATZD, PV, TZV and DRE between the patients with cancer and the non-cancer patients. The ROC curve analysis revealed that PV, TZV, PSAD and PSATZD had significant predictive values as compared with that of PSA. However, there was no difference in AUC between them. The stepwise logistic regression analysis showed that the age, PV, PSATZD and DRE had significant predictive values, and that PSATZD had the most predictive power. In conclusion, both PSAD and PSATZD had significant predictive values in discriminating prostate cancer. Furthermore, the stepwise logistic regression analysis showed that PSATZD had the strongest predictive value. PMID- 17339879 TI - The choice of model organisms in evo-devo. AB - Study of the model organisms of developmental biology was crucial in establishing evo-devo as a new discipline. However, it has been claimed that this limited sample of organisms paints a biased picture of the role of development in evolution. Consequently, judicious choice of new model organisms is necessary to provide a more balanced picture. The challenge is to determine the best criteria for choosing new model organisms, given limited resources. PMID- 17339880 TI - Cancer epigenomics: DNA methylomes and histone-modification maps. AB - An altered pattern of epigenetic modifications is central to many common human diseases, including cancer. Many studies have explored the mosaic patterns of DNA methylation and histone modification in cancer cells on a gene-by-gene basis; among their results has been the seminal finding of transcriptional silencing of tumour-suppressor genes by CpG-island-promoter hypermethylation. However, recent technological advances are now allowing cancer epigenetics to be studied genome wide - an approach that has already begun to provide both biological insight and new avenues for translational research. It is time to 'upgrade' cancer epigenetics research and put together an ambitious plan to tackle the many unanswered questions in this field using epigenomics approaches. PMID- 17339881 TI - Gene therapy progress and prospects: ultrasound for gene transfer. AB - Ultrasound exposure (USE) in the presence of microbubbles (MCB) (e.g. contrast agents used to enhance ultrasound imaging) increases plasmid transfection efficiency in vitro by several orders of magnitude. Formation of short-lived pores in the plasma membrane ('sonoporation'), up to 100 nm in effective diameter lasting a few seconds, is implicated as the dominant mechanism, associated with acoustic cavitation. Ultrasound enhanced gene transfer (UEGT) has also been successfully achieved in vivo, with reports of spatially restricted and therapeutically relevant levels of transgene expression. Loading MCB with nucleic acids and/or disease-targeting ligands may further improve the efficiency and specificity of UEGT such that clinical testing becomes a realistic prospect. PMID- 17339883 TI - Arabidopsis AtBECLIN 1/AtAtg6/AtVps30 is essential for pollen germination and plant development. AB - Pollen germination on the surface of compatible stigmatic tissues is an essential step for plant fertilization. Here we report that the Arabidopsis mutant bcl1 is male sterile as a result of the failure of pollen germination. We show that the bcl1 mutant allele cannot be transmitted by male gametophytes and no homozygous bcl1 mutants were obtained. Analysis of pollen developmental stages indicates that the bcl1 mutation affects pollen germination but not pollen maturation. Molecular analysis demonstrates that the failure of pollen germination was caused by the disruption of AtBECLIN 1. AtBECLIN 1 is expressed predominantly in mature pollen and encodes a protein with significant homology to Beclin1/Atg6/Vps30 required for the processes of autophagy and vacuolar protein sorting (VPS) in yeast. We also show that AtBECLIN 1 is required for normal plant development, and that genes related to autophagy, VPS and the glycosylphosphatidylinositol anchor system, were affected by the deficiency of AtBECLIN 1. PMID- 17339884 TI - Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9. AB - The apoptosis of lens epithelial cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial (HLE) cells and the possible molecular mechanisms involved. HLE cells (SRA01-04) were incubated with 50 microM H(2)O(2) in the absence or presence of different doses of parthenolide (10, 20 and 50 microM). To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H(2)O(2) for 18 h, a high fraction of HLE cells underwent apoptosis, while in the presence of parthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H(2)O(2) in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation of caspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation of caspase-3 and caspase-9, suggesting a potential protective effect against cataract formation. PMID- 17339885 TI - Gender differences in QTc interval in young, trained individuals with lower spinal cord injury. AB - STUDY DESIGN: Cross-sectional comparison. OBJECTIVE: To examine gender differences in rate-corrected QT interval (QTc), an index of ventricular depolarization/repolarization, in young, trained men and women with lower spinal cord injury (SCI) and able-bodied (AB) controls. SETTING: University of Illinois at Urbana-Champaign, Exercise and Cardiovascular Research Lab, USA. METHODS: Subjects consisted of 16 athletes with SCI (eight men and eight women) and 16 age matched AB active controls (eight men and eight women). QT interval dynamics was derived from ECG recordings and rate corrected using the Bazett formula. RESULTS: Men with SCI had QTc similar to that of AB men (369.3+/-7.5 versus 357.9+/-3.0 ms, P>0.05). Women with SCI had QTc similar to that of AB women (400.0+/-4.6 versus 385.2+/-6.5 ms, P>0.05). AB women had longer QTc interval than AB men, and SCI women had longer QTc than SCI men (P<0.05). CONCLUSIONS: Gender differences in ventricular depolarization/repolarization are present in trained individuals with SCI. Thus, similar to their AB gender-matched peers, women with SCI have longer QTc intervals and may be at greater risk for the development of untoward cardiac arrhythmias than men with SCI. PMID- 17339886 TI - Actinomycosis of the neck causing cervical epidural cord compression. 'A case report and review of literature'. AB - OBJECTIVE AND IMPORTANCE: Involvement of cervical spinal cord by Actinomycosis and consequent cord compression is a rare presentation. As the organism is located in nose and throat, the face and jaw area is commonly affected. Involvement of cervical cord has been rarely recorded. We are reporting this case because of the rarity of area of the involvement and have reviewed literature. CLINICAL PRESENTATION: A 30-year-old male with multiple discharging sinuses on the nape of neck and upper back for 7 years which resulted in cervical cord compression and spastic paraperesis. Tissue biopsy from the site of discharging sinuses revealed Actinomycosis. Patient responded to the medical therapy with penicillin and power in lower limbs was improved. The local lesion was also reduced. INTERVENTION: Medical therapy with penicillin and surgical decompression forms the mainstay of treatment. CONCLUSION: A high degree of suspicion and demonstration of organism by biopsy or culture is essential for treatment. Penicillin is highly effective and should be given for long duration for optimal results. PMID- 17339887 TI - Measurement of coronary artery calcification by electron beam computerized tomography in persons with chronic spinal cord injury: evidence for increased atherosclerotic burden. AB - BACKGROUND/OBJECTIVE: Individuals with spinal cord injury (SCI) have been reported to have an increased prevalence of premature cardiovascular disease. Whether the increased risk of disease is owing to clustering of traditional cardiac risk factor or is over and above that predicted by risk factors was addressed. METHODS: Ninety-one persons with chronic SCI were studied for subclinical atherosclerosis. Cardiac risk factors and coronary artery calcium (CAC) was compared to matched non-SCI controls. The 273 controls were 3:1 matched for age, gender, ethnicity and risk factors and were drawn from a national database of over 30,000 asymptomatic persons undergoing coronary scanning. RESULTS: Seventy-six men and 15 women were studied. Average age was 49.7+/-12 years. Duration of injury was 19.7+/-10 years. The ethnicity of the study cohort included 36% Caucasian, 49% Latino, 10% African American, and 5% other. The mean calcium score of the SCI group was significantly greater than the control group (75+/-218 versus 28+/-104, P<0.001). The prevalence of any CAC score was greater in the SCI population than the control population (51 versus 39%, P<0.05), as was CAC score >100 (16 versus 7%, P<0.01). Women with SCI had a significantly lower CAC score than men (mean score: 12 versus 86, P<0.01). CONCLUSION: Patients with SCI were shown to have greater atherosclerotic burden than able-bodied controls. Of note, and unexplained, this finding is beyond that explained by the clustering of traditional risk factors. On the basis of these findings, increased attention should be directed toward the prevention of coronary heart disease in those with SCI. PMID- 17339888 TI - Spinal cord and related injuries after attempted suicide: psychiatric diagnosis and long-term follow-up. AB - STUDY DESIGN: Retrospective analysis of acute spinal cord injuries (ASCI). OBJECTIVES: Determine incidence of ASCI due to suicide attempt from 1970 to 2000. Describe demographics, injuries, mental illness, functional outcomes and nature of subsequent deaths. SETTING: State spinal cord injury services, New South Wales, Australia. METHODS: Retrospective record review and follow-up interview. RESULTS: Of 2752 ASCI admissions, 56 were because of attempted suicide (55 falls, one gun-shot wound). Thirty-six males and 20 females. Median age 30 years (15 74). Most common levels of vertebral injury were C5 and L1. Twenty-three had complete spinal cord injury. Thirty-two had an Injury Severity Score of >15. Forty had more than one major injury. There was a significant rise in the incidence of ASCI following self-harm over time (Poisson regression, P=0.004). There was a significant change in scene of injury away from hospitals over time (chi (2) test, df=1, P=0.0001). Psychiatric diagnoses were personality disorder 27; schizophrenia 16; depression 14; chronic alcohol abuse 10; mood disorder 10; chronic substance abuse 10; other four. Follow-up was available in 47 cases (84%) at an average of 8 years. Four subsequent deaths were by suicide. Domiciliary arrangements were: home 28; hospital five; nursing home three; group home/hostel four. CONCLUSIONS: Community placement outcomes for survivors were good. Subsequent death by suicide was high. There was a significant rise in cases and a change in injury scene away from hospitals over time. PMID- 17339889 TI - The feasibility of sleep assessment by actigraph in patients with tetraplegia. AB - BACKGROUND: Sleep disturbances are frequent in patients with high spinal cord lesions, and are difficult to diagnose by means of polysomnography (PSG). DESIGN: Retrospective cohort study. OBJECTIVE: Examine the feasibility of sleep assessment by actigraph in patients with tetraplegia. SETTING: A rehabilitation center in Israel. SUBJECTS: Twenty-one patients with tetraplegia and 20 healthy persons. INTERVENTIONS: Sleep assessment by actigraphs attached to the head and the wrist. MAIN OUTCOME MEASURES: The actigraphic movement index (MI), total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), sleep latency (SL), and number of awakenings (NOA). RESULTS: In the control group actigraphy showed that during sleep the hand moves more than the head but that the movements were highly correlated. In patients with tetraplegia below C(5) C(7) the hand also moved more than the head, but in patients with tetraplegia below C(4), the head moved more (P<0.05). No significant differences were found between patients with C(5)-C(7) tetraplegia and healthy controls in the sleep indices obtained by hand movements, or between patients with C(4) tetraplegia and healthy controls in the indices obtained by head movements. Control subjects and patients showed similar subjective assessment of sleep quality. CONCLUSIONS: These preliminary findings support the validity of wrist actigraphy for sleep assessment in patients with C(5)-C(7) tetraplegia, and suggest that head-mounted actigraphy is a feasible alternative for sleep assessment in patients with tetraplegia below C(4). To establish these findings, further investigations are required, with a larger number of patients and comparison with PSG. PMID- 17339890 TI - Calcitonin gene-related peptide immunoreactivity in chronic human spinal cord injury. AB - STUDY DESIGN: Histopathological study of the human spinal cord. SETTING: International Collaboration on Repair Discoveries, Vancouver, BC, Canada. RATIONALE: In animals, primary dorsal root afferent fibers, which are immunoreactive for calcitonin gene-related peptide (CGRP), sprout following spinal cord injury (SCI) into deeper laminas of the dorsal horn below the level of injury. It has been suggested that this aberrant sprouting plays a role in altering cardiovascular control after SCI and could be responsible for life threatening episodes of autonomic dysreflexia (AD). OBJECTIVES: To observe the changes of CGRP distribution after SCI and compare the differences between normal and injured human spinal cord. METHODS: Upper thoracic segments from individuals with chronic cervical SCI (n=4) and individuals with intact spinal cords (n=5) were processed immunocytochemically to identify CGRP fibers and histologically to identify the severity of degeneration. RESULTS: Semiquantitative analysis showed a significant increase in CGRP immunoreactivity in the dorsal horns of individuals with chronic SCI (P<0.001). Furthermore, one of the SCI individuals in this study displaying significant CGRP sprouting had well documented episodes of AD. CONCLUSIONS: Our observations suggest that SCI in humans results in significant sprouting of CGRP fibers. This aberrant sprouting of sensory fibers could contribute to the abnormal cardiovascular control and pain commonly observed following chronic human SCI. PMID- 17339891 TI - Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels. AB - Colorectal cancer (CRC) resistance to fluoropyrimidines and other inhibitors of thymidylate synthase (TS) is a serious clinical problem often associated with increased intracellular levels of TS. Since the tumour suppressor gene p53, which is mutated in 50% of CRC, regulates the expression of several genes, it may modulate TS activity, and changes in the status of p53 might be responsible for chemoresistance. Therefore, this study was aimed to investigate TS levels and sensitivity to TS inhibitors in wild-type (wt) and mutant (mt) p53 CRC cells, Lovo and WiDr, respectively, transfected with mt and wt p53. Lovo 175X2 cells (transfected with mt p53) were more resistant to 5-fluorouracil (5-FU; 2-fold), nolatrexed (3-fold), raltitrexed (3-fold) and pemetrexed (10-fold) in comparison with the wt p53 parental cells Lovo 92. Resistance was associated with an increase in TS protein expression and catalytic activity, which might be caused by the loss of the inhibitory effect on the activity of TS promoter or by the lack of TS mRNA degradation, as suggested by the reversal of TS expression to the levels of Lovo 92 cells by adding actinomycin. In contrast, Lovo li cells, characterized by functionally inactive p53, were 3-13-fold more sensitive to nolatrexed, raltitrexed and pemetrexed, and had a lower TS mRNA, protein expression and catalytic activity than Lovo 92. However, MDM-2 expression was significantly higher in Lovo li, while no significant differences were observed in Lovo 175X2 cells with respect to Lovo 92. Finally, mt p53 WiDr transfected with wt p53 were not significantly different from mt p53 WiDr cells with respect to sensitivity to TS inhibitors or TS levels. Altogether, these results indicate that changes in the status of p53, can differently alter sensitivity to TS inhibitors by affecting TS levels, depending on activity or cell line, and might explain the lack of clear correlation between mutations in p53 and clinical outcome after chemotherapy with TS inhibitors. PMID- 17339892 TI - Breastfeeding and risk of childhood CNS tumours. AB - We investigated infant feeding habits in relation to risk of childhood central nervous system tumours among 633 cases in the UK Childhood Cancer Study (UKCCS). No significant effect of breastfeeding was detected overall (odds ratio 1.01, confidence interval: 0.85-1.21) nor in any morphological subgroup. Similarly, no effect for the duration of breastfeeding or any other feeding practices was observed. PMID- 17339893 TI - Widening socio-economic inequalities in oral cancer incidence in Scotland, 1976 2002. AB - Oral cancer incidence was investigated among 10 857 individuals using Scottish Cancer Registry data. Since 1980 the incidence of oral cancer among males in Scotland has significantly increased, the rise occurring almost entirely in the most deprived areas of residence. PMID- 17339895 TI - Warrior genes and risk-taking science. AB - This article provides a summary of our ethical concerns regarding the so-called "warrior gene" line of research. Prompted by recent claims that there is a genetic explanation for negative social and health statistics for Maori, the article discusses issues related to informed consent of research participants, the validity of the underlying science related to the "warrior gene", and scientifically unfounded speculation regarding the causality of complex social issues. We conclude that in all science, and particularly where there is a highly charged social and political setting, the scientist has a responsibility for the way in which findings are disseminated and for ensuring a clear public understanding of the limitations of the work. PMID- 17339896 TI - Risk-taking: behind the warrior gene story. AB - In 2006, the monoamine oxidase-A gene was widely reported in the media as being associated with risk-taking and aggressive behaviour in Maori. We examine the scientific evidence underlying this claim. Whilst there is credible evidence for a contribution of a monoamine oxidase-A genetic variant to antisocial behaviour in Caucasians, there is no direct evidence to support such an association in Maori. Insufficient rigour in interpreting and applying the relevant literature, and in generating new data, has (in conjunction with a lack of scientific investigative journalism) done science and Maori a disservice. PMID- 17339897 TI - Monoamine oxidase, addiction, and the "warrior" gene hypothesis. PMID- 17339898 TI - The Health and Safety in Employment Act and the influenza vaccination of healthcare workers. AB - Despite studies demonstrating that the annual influenza vaccination of healthcare workers has a statistically significant reduction of morbidity and mortality among the patients they care for, and District Health Boards (DHBs) establishing voluntary programs to provide the influenza vaccine to healthcare workers free of charge, vaccination rates among healthcare workers are dismal, with only about 20%-40% coverage rates being achieved. With these low rates posing a serious health threat to the vulnerable patient populations that are entrusted into healthcare workers' care, and the current voluntary programmes clearly failing to adequately address this issue, we believe the time has come for the annual influenza vaccination to be made a mandatory requirement for all healthcare workers with direct patient contact unless a medical contraindication exists. Indeed, a compelling case may be made that the duties imposed on DHBs and healthcare workers under the Health and Safety in Employment Act 1992 requires making the annual influenza vaccination an occupational requirement. PMID- 17339899 TI - Improving Maori health outcomes with decision support. PMID- 17339900 TI - Maori and non-Maori differences in caesarean section rates: a national review. AB - AIM: To investigate the relationship between caesarean section (CS), deprivation, and ethnicity; and to examine Maori/non-Maori differences in CS after controlling for possible confounding factors. METHOD: Total, acute, and elective CS rates (as proportions of women giving birth in New Zealand hospitals) during 1997-2001 were examined by ethnicity and area deprivation. Logistic regression was used to adjust for age, deprivation, some clinical factors, and District Health Board (DHB). RESULTS: Total, acute, and elective CS rates were significantly higher among non-Maori compared to Maori women (total CS, 21% vs 13%, ratio 1.59, p<0.0001). CS rates decreased with increasing levels of deprivation. After controlling for deprivation and age, differences between Maori (M) and non-Maori (nM) remained (total CS odds ratio nM:M 1.43, 95% confidence interval 1.39-1.48; elective OR 1.44 (1.36-1.52); acute OR 1.38 (1.33-1.43)). Differences also remained after controlling for other factors including a limited number of clinical factors. CONCLUSION: Results suggest that non-clinical factors may be contributing to ethnic differences in CS in New Zealand. While deprivation contributes to this difference it does not fully explain it. Further research is needed to investigate whether ethnic differences in CS impact on birth outcomes, and which factors, other than those clinically indicated, contribute to ethnic differences in caesarean section in New Zealand. PMID- 17339901 TI - Assessing Maori/non-Maori differences in cardiovascular disease risk and risk management in routine primary care practice using web-based clinical decision support: (PREDICT CVD-2). AB - AIM: To describe the cardiovascular disease risk factor status and risk management of Maori compared with non-Maori patients opportunistically assessed in routine practice using PREDICT-CVD, an electronic clinical decision support programme. METHODS: In August 2002, a primary healthcare organisation, ProCare, implemented PREDICT-CVD as an opportunistic cardiovascular risk assessment and management programme. Between 2002 and February 2006, over 20,000 cardiovascular risk assessments were undertaken on Maori and non-Maori patients. Odds ratios and mean differences in cardiovascular risk factors and risk management for Maori compared to non-Maori (European and other, Pacific, Indian, and other Asian) patients were calculated. RESULTS: Baseline risk assessments were completed for 1450 (7%) Maori patients and 19, 164 (93%) non-Maori patients. On average, Maori were risk assessed 3 years younger than non-Maori. Maori patients were three times more likely to be smokers, had higher blood pressure and TC/HDL levels, and twice the prevalence of diabetes and history of cardiovascular disease as non Maori. Among patients with a personal history of cardiovascular disease, Maori were more likely than non-Maori to receive anticoagulants, blood pressure lowering and lipid-lowering medications. However, of those patients with a history of ischaemic heart disease, Maori were only half as likely as non-Maori to have had a revascularisation procedure. CONCLUSION: An electronic decision support programme can be used to systematically generate cardiovascular disease risk burden and risk management data for Maori and non-Maori populations in routine clinical practice in real-time. Moreover, the PREDICT-CVD programme has established one of the largest cohorts of Maori and non-Maori ever assembled in New Zealand. Initial findings suggest that Maori are more likely than non-Maori to receive drug-based cardiovascular risk management if they have a personal history of cardiovascular disease. In contrast, among the subgroup of patients with a history of ischaemic heart disease, Maori appear to receive significantly fewer revascularisations than non-Maori. PMID- 17339902 TI - Is it possible to distribute a scarce resource equitably? Access to invasive procedures for patients with acute myocardial infarction. AB - AIMS: To compare waiting times for inpatient cardiac catheterisation between a hospital with on-site cardiac catheterisation facility (Auckland City Hospital, ACH) and one of its referring hospitals (North Shore Hospital, NSH). METHODS: Patients were included if they were admitted ACH or NSH with a myocardial infarction, and subsequently underwent inpatient coronary angiography. RESULTS: 853 patients were identified from NSH and 600 from ACH. Patients from NSH waited significantly longer for coronary angiography (median delay 6 versus 3 days, p<0.0009) and fewer underwent this procedure within 48 hours of admission (11% versus 36%, p<0.0009). Delays in percutaneous coronary intervention were significantly longer for NSH patients (6 versus 3 days, p<0.0009), and fewer NSH patients underwent this procedure within 48 hours (12% versus 41%, p<0.0009). CONCLUSIONS: Inpatients with myocardial infarction waited longer for coronary angiography and percutaneous coronary intervention at a hospital without invasive facility than similar patients at the regional referral hospital with on-site invasive facility. PMID- 17339903 TI - A boy with a limp. Slipped capital femoral epiphysis. PMID- 17339904 TI - Beware of infants with respiratory distress, rash, and hepatomegaly at birth: a case of congenital syphilis. PMID- 17339905 TI - Snakes alive! Caput medusae due to cerebral venous angioma. PMID- 17339906 TI - Improving care to stroke patients: adding an acute stroke unit helps. AB - BACKGROUND: Stroke units save lives, reduce dependency, and increase the chance of returning home. A 15-bed Acute Stroke Unit (ASU) was opened on the acute hospital campus to complement an established Stroke Rehabilitation Unit (SRU) on a distant campus. The aim of this study was to address whether patient care was improved with the establishment of the ASU. METHODS: Retrospective case-note review of a sample of patients admitted with an acute stroke to Christchurch Hospital. A before and after design was utilised to audit the processes of care (PoC) using the Royal College of Physicians (London) stroke audit tool. RESULTS: 648 patients were admitted to the Acute Stroke Unit in the first year. The retrospective audit included 119 and 72 patients in the "before" and "after" cohorts respectively. The "after" cohort had more severe strokes (greater incontinence at one week, [p=0.03], and worse level of consciousness [p=0.008]). Length of stay, domicile on discharge, and mortality outcomes were similar for the two cohorts. Processes of care improved in the "after" cohort in 27 of the 43 domains audited. CONCLUSION: Adding an ASU to complement an existing SRU can give major improvements in PoC across many different facets of stroke care. We believe this is one step closer to both the ideals of an overall coordinated stroke service and better overall care for patients with stroke. PMID- 17339907 TI - Talking health, doing harm: New Zealand Government investment in industries that kill. PMID- 17339908 TI - PHARMAC and statins--correction is needed. PMID- 17339909 TI - Vasectomy procedures. PMID- 17339910 TI - Equine gastric ulcer syndrome in adult horses: a review. AB - In recent years, gastric ulceration has been recognised as a common, possibly performance-limiting disease of adult horses. Here, we aim to provide the reader with a useful review of recent literature covering all aspects of equine gastric ulcer syndrome (EGUS) in adult horses. The anatomy and physiology of the stomach, with particular reference to secretion of acid and mucosal protective mechanisms, are reviewed, as are the differing theories relating to the aetiopathogenesis of gastric ulceration. We also explore the possible influence of various management factors on development of the disease. The prevalence of the disease in racehorses has been reported to be as high as 100%. In general, horses that are in active training for racing tend to have a prevalence of around 90%, whereas pleasure horses in full work have a reported prevalence of approximately 60%. Emerging diagnostic tests which could obviate the need for gastroscopy are introduced and current recommendations for treatment are summarised, focussing on proton pump inhibitors, in particular omeprazole, administered orally. The oral administration of omeprazole has been shown to be effective in both treating horses with gastric ulceration and at preventing re-occurrence whilst the horses are in training, provided that daily dosing is maintained. PMID- 17339911 TI - The prevalence of gastric ulceration in racehorses in New Zealand. AB - AIM: To establish the prevalence and factors influencing the prevalence and severity of gastric ulceration in racehorses in New Zealand. METHODS: Horses (n=171) in active training for racing by trainers (n=24) located throughout New Zealand were examined using gastroscopy during 2003 and 2004. Images of the examination were recorded and reviewed, and an ordinal grade based on the severity of gastric ulceration present was assigned, using the grading system proposed by the Equine Gastric Ulcer Council (EGUC). Information about the horses such as age, breed, sex, stabling, time at pasture, pasture quality, and presence of clinical signs consistent with equine gastric ulcer syndrome (EGUS) was recorded. RESULTS: Of the 171 horses in the study, 133 (78%) were Thoroughbreds and 38 (22%) were Standardbreds. Evidence of gastric ulceration was present in 151 (88.3%) of these. Prevalence of ulceration was higher at the lesser curvature (LC) and greater curvature (GC) of the stomach than at the saccus caecus (SC; p<0.01), and ulceration was more severe at the LC than at either the GC (p=0.02) or the SC (p<0.001). The prevalence of ulceration did not differ between the two breeds (p=0.51) or between horses of differing ages (p=0.56). Gastric ulceration was evident in 125/141 (89%) horses kept at pasture for at least 4 h/day, in all 13 (100%) horses kept at pasture full time, and in 16/17 (94%) horses stabled full time. Prevalence and severity of ulceration did not differ between horses stabled full time, kept at pasture for part of the day or kept at pasture full time (p=0.33 and 0.13, respectively), and for horses grazed on pasture severity of ulceration did not vary significantly with the quality of the pasture (p=0.12). Neither prevalence (p=0.26) nor severity (p=0.49) of gastric ulceration varied significantly with duration of training. CONCLUSIONS: The prevalence of gastric ulceration in racehorses in New Zealand is similar to that reported elsewhere for horses in active training for racing. Access to pasture for some or all of the day did not appear to be protective. PMID- 17339912 TI - A comparison of two scoring systems for endoscopic grading of gastric ulceration in horses. AB - AIM: To compare two scoring systems for grading gastric ulcers in adult horses. METHODS: Digitised recordings of gastroscopy examinations of 22 horses that were part of a study on prevalence of gastric ulceration in racehorses in New Zealand were reviewed independently by three examiners. All stomachs were graded by each examiner using two different grading systems, the Equine Gastric Ulcer Council (EGUC) system and the Number/Severity (N/S) system. RESULTS: All examiners commented that the EGUC system was quicker and easier to use. There was no significant difference between examiners in the grades assigned using the EGUC system (p=0.31) and the agreement between examiners was high (Kappa values of 0. 85(1vs2), 0.88(1vs3) and 0.80(2vs3)). There was a significant difference between examiners in the grades assigned using the severity component of the N/S system (p=0.005). CONCLUSIONS: The EGUC system was more repeatable, and was faster and easier to use than the N/S system. CLINICAL RELEVANCE: The EGUC system is suitable as a standard scoring system due to its ease of use, and the repeatability and correlation of grades assigned between independent examiners. Use of a standard scoring system will more easily allow comparisons to be made between different research groups and clinicians. PMID- 17339913 TI - Experimental infections in young red deer (Cervus elaphus) with a bovine and an ovine strain of Mycobacterium avium subsp paratuberculosis. AB - AIMS: To compare the virulence of a 'bovine' and an 'ovine' strain of Mycobacterium avium subsp paratuberculosis (M. ptb) in red deer (Cervus elaphus) after experimental inoculation orally, and to examine the relationship between the dose of the bovine strain given and immunological, clinical and histopathological outcomes in young red deer. METHODS: Newly-weaned 4-month-old male red deer (n=81) were randomly assigned to one of five groups. Three groups (n=16) received high (10(9) colony forming units (cfu); HB), medium (10(7) cfu; MB) or low (10(3) cfu; LB) oral doses of a bovine strain of M. ptb, one group (n=16) received medium (10(7) cfu; MO) doses of an ovine strain of M. ptb, and a Control group (n=17) was not dosed. The HB and Control groups were grazed together, the MB and LB groups were grazed together, and the MO group was grazed alone, in separate small paddocks on a quarantined area of the farm for 45 weeks. Liveweight, clinical signs and immunoglobulin G1 (IgG1) antibody levels were monitored for up to 45 weeks. Deer affected with Johne's disease were euthanised when they showed obvious clinical signs. Unaffected deer were slaughtered at the end of the trial (Week 45), and all deer were necropsied. Faeces and tissue samples were cultured for M. ptb, and fixed tissues were examined for histopathology. RESULTS: Between 21 and 38 weeks post-challenge (pc), 5/16 animals in the HB group developed early signs of Johne's disease and were euthanised. The remaining deer in the five groups were all apparently healthy and reached good liveweights (approximately 100 kg average), and were euthanised and examined 45 weeks pc. Three deer (two HB and one MB) had small caseous lesions in their jejunal lymph nodes (JJLNs) and one HB animal had a small caseous lesion in a retropharyngeal lymph node. The remaining animals had no grossly-visible lesions. Mycobacterium avium subsp paratuberculosis was cultured from samples from 100% of the HB and MB animals, 50% of the LB group, 69% of the MO group and all Control animals. Thus all Control deer were infected by natural transmission from the HB group but none developed signs of clinical disease. Examination of histological sections of jejunum, ileocaecal valve (ICV) and associated lymph nodes showed a gradation of severity of lesions that was positively correlated (p<0.001) with dose of the bovine strain administered; mean lesion severity scores were 4.8, 2.9 and 0.9 for HB, MB and LB groups, and 2.2 and 0.9 for the Control and MO groups, respectively. IgG1 antibody levels at the time of euthanasia were also correlated with lesion severity scores at slaughter (p<0.001). CONCLUSIONS: The ovine strain of M. ptb used in this study was less virulent for red deer than the bovine strain. The correlation between dose of the bovine strain and the severity of lesions suggests that clinical Johne's disease in yearling red deer likely results from high oral challenge with a bovine strain whilst they are young. The minimum oral infective dose may be close to 10(3) cfu for this bovine strain. PMID- 17339914 TI - Survey on 'lumpy jaw' on deer farms in western Canada: prevalence and distribution, and identification of associated factors. AB - AIM: To investigate the prevalence and geographical distribution of 'lumpy jaw' (LJ) in a population of white-tailed deer (WTD; Odocoileus virginianus) and mule deer (MD; Odocoileus hemionus) farms from the western Canadian provinces of Saskatchewan and Alberta, and to identify factors associated with its occurrence. METHODS: A cross-sectional study, in which the target population was all farmers of WTD and MD registered in Saskatchewan and Alberta, was conducted between July 2004 and January 2005. A questionnaire was mailed to all farmers requesting information about the presence of LJ and other necrobacillosis- related syndromes (footrot and fawn death syndrome), and various farm characteristics, during 2002, 2003 and 2004. Herd and within-herd incidences of disease were estimated. Global and local spatial analyses were performed to identify possible clusters of occurrence of LJ in the region. Logistic regression analysis was used to identify factors associated with the occurrence of LJ. RESULTS: A total of 139/268 (52%) deer farmers responded to the survey. Over the entire study period, 108/139 (78%) of farmers reported having cases of LJ in their herds, and in any given year the incidence amongst herds was about 40%. The presence of footrot was not associated with the presence of LJ. The proportion of fawns dying suddenly in 2004 was higher on farms affected by LJ than in those considered LJ-free (median of 11.1% and 0%, respectively; p<0.001). Two areas in Saskatchewan were identified as having a higher herd prevalence of LJ (clusters) than all other areas. Density of animals, moving and handling animals, lack of basic hygiene measures, and bottle- feeding of fawns increased the odds of a herd being affected by LJ. CONCLUSIONS AND CLINICAL RELEVANCE: LJ should be considered a common disease in farmed deer in western Canada. The observed relationship between the occurrence of LJ and acute mortality of fawns emphasises the potential of this infection to result in significant economic loss. Intensive management of deer, characterised by high densities and frequent moving and handling of animals, may contribute significantly to the occurrence of LJ. Observed geographical clusters may reflect areas where management of deer was more intensive or the trading of deer more common. PMID- 17339915 TI - The effects of radial shock waves on the metabolism of equine cartilage explants in vitro. AB - AIM: To investigate, in vitro, the effects of radial shock waves on the release of nitric oxide (NO) and synthesis of prostaglandin E2 (PGE2) and glycosaminoglycan (GAG), and liberation of GAG, from equine articular cartilage explants. METHODS: Equine cartilage from normal metacarpophalangeal and metatarsophalangeal joints was exposed to radial shock waves at various impulse doses and then maintained as explants in culture for 48 h. Shock waves were delivered at 1,876 Torr pressure and a frequency of 10 Hz. Treatment groups consisted of a negative control group, or application of 500, 2,000, or 4,000 impulses by use of either a convex handpiece (Group A) or concave handpiece (Group B). Synthesis of GAG was measured using incorporation of 35S-labelled sodium sulphate. Additionally, the synthesis of NO and PGE2, and content of GAG of the explants and media were determined. RESULTS: No significant effects (p>0.05) of radial shock-wave treatment were evident on the synthesis of NO or PGE2, or release of GAG by cartilage explants. However, radial shock waves decreased synthesis of GAG measured 48 h after exposure for all treatment groups other than the 500-impulse Group-A explants (p<0.05). CONCLUSIONS: Radial shock waves impact the metabolism of GAG in chondrocytes in equine articular cartilage. Further studies will be required to fully investigate the impact of this effect on the health of joints, and to elucidate the clinical impact. PMID- 17339918 TI - Aperture synthesis in phase retrieval using a volume-speckle field. AB - The resolution of the reconstructed wave by a phase-retrieval method using a volume-speckle field depends on the aperture defined by the size of the CCD array. The use of a larger aperture is introduced by measuring the speckle field at two different positions in the transverse plane and stitching the measurements together. Improvements in the quality of reconstructions are demonstrated experimentally and by computer simulations. Undesirable effects of camera tilt on the quality of reconstructions from synthetic aperture intensity measurements are experimentally observed and corrected. PMID- 17339916 TI - Evaluation of two commercial enzyme-linked immunosorbent assays for detection of bovine viral diarrhoea virus in serum and skin biopsies of cattle. AB - AIM: To assess the ability of two commercial bovine viral diarrhoea (BVD) virus (BVDV) antigen-capture enzyme-linked immunosorbent assays (ELISAs) to detect virus in serum and skin biopsies. METHODS: Thirty cattle persistently infected (PI) with BVDV were identified using routine diagnostic laboratory testing. Additional ear-notch skin biopsies and blood samples were collected from these animals to confirm the diagnosis, and from 246 cohorts, to determine their BVDV status. Skin biopsies were soaked overnight in buffer and the eluate collected. All sera and eluate were tested using two commercially available ELISAs for detecting BVDV antigen, and a subsample of positive and negative sera was tested using a polymerase chain reaction (PCR) test. A study was also performed to ascertain the risk of cross contamination occurring during the collection and processing of skin biopsies. RESULTS: Both serum and skin samples tested using either ELISA resulted in the detection of all cattle identified as PI and no non infected cattle were incorrectly classified as infected using either method. Agreement between all assays (ELISAs, whether performed on serum or skin, and PCR) was 100%. No cross-contamination of skin samples between animals was evident using routine biopsy methods. CONCLUSIONS: Viraemic cattle infected with BVDV were accurately identified using either of the two commercial ELISAs evaluated on either serum or skin samples. CLINICAL RELEVANCE: Either skin biopsies or serum samples can be collected from cattle to determine their BVDV status. This should overcome problems in accurately identifying the infection status of young calves in which colostral antibodies might interfere with the antigen-capture ELISA. PMID- 17339919 TI - Spatial information transmission using axial temporal coherence coding. AB - We present an approach that can be used for transmission of information through space-limited systems or for superresolution. The spatial information is coded with different axial temporal coherence by interfering every spatial region in the input with the same region, but with a certain known delay in the longitudinal axis. Every spatial region has different delay. After mixing all of the spatial information, it is transmitted through the space-limited system. At the detection the information is passed through a similar interference setup containing certain axial delay. By temporally scanning along the longitudinal axis, each time a different spatial region that was coded with the corresponding axial delay is reconstructed. To allow coding of different spatial regions with different and small axial delays, we use a thermal light source that has very short coherence length. We include experimental validation of the presented approach. PMID- 17339920 TI - Estimation precision of the degree of polarization from a single speckle intensity image. AB - We address the problem of the estimation of the degree of polarization from a single intensity image. For that purpose, one considers the case of coherent active imagery that leads to speckle fluctuations and assumes that the measured intensity image corresponds to a fully developed speckle for each polarized component of the electric field. In particular, we determine the Cramer-Rao bound of the degree of polarization estimation and propose to illustrate this result by analyzing the variance of different simple estimators. PMID- 17339921 TI - Hypergeometric modes. AB - A new family of paraxial laser beams that form an orthogonal basis is discussed. When propagated in uniform space, these beams preserve their structure to scale. The intensity distribution profile for such beams is similar to that for the Bessel modes, representing a set of alternating bright and dark concentric rings. The complex amplitude of these beams is proportional to the degenerate (confluent) hypergeometric function, and therefore we term such beams hypergeometric (HyG) modes. The HyG modes are generated with a liquid-crystal microdisplay. PMID- 17339922 TI - Photonic microwave phase shifter/modulator based on a nonlinear optical loop mirror incorporating a Mach-Zehnder interferometer. AB - We realize a novel photonic microwave phase shifter/modulator based on a nonlinear optical loop mirror incorporating a Mach-Zehnder interferometer. A near linear phase shifter exceeding 180 degrees and a phase modulation with 2.5 Gbit/s baseband signal are obtained for a 10 GHz microwave signal by this proposed device. PMID- 17339923 TI - Natural bend-distortion immunity of higher-order-mode large-mode-area fibers. AB - Bend-induced distortion is an important limitation in the development of fibers with very large mode areas. Simulations demonstrate that higher-order modes, recently proposed for amplification, are naturally immune to bend distortion, despite their extremely large mode areas. These numerical results compliment measured resistance to mode coupling. An interesting indirect coupling between nearly degenerate modes is shown to dominate the distortion. PMID- 17339924 TI - Cross-phase-modulation-based wavelength conversion using intersubband transition in InGaAs/AlAs/AlAsSb coupled quantum wells. AB - We report an ultrafast cross phase modulation (XPM) effect in intersubband transition (ISBT) of InGaAs/AlAs/AlAsSb coupled quantum wells, where the ISBT absorption of a transverse-magnetic mode pump signal induces phase modulation of a transverse-electric mode probe signal. Using waveguide-type ISBT devices, we have achieved XPM-based 10 Gbit/s wavelength conversion with a power penalty of 2.53 dB. Also, we propose XPM-based signal processing circuits for gate switching and modulation format conversion. PMID- 17339925 TI - Thinnest optical waveguide: experimental test. AB - A thin dielectric waveguide with a subwavelength diameter can exhibit very small transmission loss only if its diameter is greater than a threshold value, while for smaller diameters, waveguide loss grows dramatically. The threshold diameter of transition between these waveguiding and nonwaveguiding regimes is primarily determined by the wavelength of propagating light and, to a much lesser degree, by the characteristic length of the waveguide's long-range nonuniformity. For this reason, the transmission spectrum of a thin waveguide allows immediate and quite accurate determination of its thickness. An experimental test of these facts is performed for a tapered microfiber. Good agreement with the recently developed theory of adiabatic microfiber tapers is demonstrated. PMID- 17339926 TI - Active control of long-period fiber-grating-based filters made in erbium-doped optical fibers. AB - Integrating an active medium with a filtering component can bring new functionalities compared with configurations where the two stages (units) are placed in series. We exploit this phenomenon and demonstrate all-optical tunable filters based on long-period fiber gratings written in an active optical fiber. The tuning is obtained via optical pumping at 980 nm. PMID- 17339927 TI - Wavelength-selective core-to-jacket coupling in optical fiber. AB - Mode coupling between the fundamental core mode of an as-drawn optical fiber operating far from cutoff and higher-order modes in the plastic jacketing has been observed. In one fiber, the transmission spectrum of the core exhibited five distinct minima between 1200 and 1900 nm. By approximating the fiber jacket as an asymmetric slab waveguide of infinite lateral extent, the wavelengths of these transmission features were successfully predicted using coupled-mode theory. Since conditions at the jacket surface influence the transmission spectrum, this coupling effect potentially enables new applications for environmental sensing. PMID- 17339928 TI - Mode shaping in multicore fibers. AB - We propose a novel multicore fiber design strategy for obtaining a flat in-phase supermode that optimizes utilization of the active medium inversion in the multiple cores. The spatially flat supermode is achieved by engineering the fiber so that the total mutual coupling between neighboring active cores is equal. Different designs suitable for different fabrication processes, such as stack-and draw and drilling, are proposed. An important improvement over previous methods is the design simplicity and better tolerance to perturbations. PMID- 17339929 TI - Comment on "Optical image encryption with Hartley transforms". AB - We numerically demonstrate that the image encryption algorithm with intensity random filtering in the Hartley domain proposed in a recent Letter by Chen and Zhao [Opt. Lett.31, 3438 (2006)] has the problem of low security. Original image information can be visually revealed only by an inverse Hartley transform without any decryption key. PMID- 17339931 TI - Shack-Hartmann sensor based on a cylindrical microlens array. AB - We present a Shack-Hartmann wavefront sensor (SHWS) based on a cylindrical microlens array as a device for measuring highly aberrated wavefronts. Instead of the typical spot pattern created by a conventional SHWS, two orthogonal line patterns are detected on a CCD and are superimposed. A processing algorithm uses the continuity of the focal line to extend the dynamic range of measurement by localizing the line, even if it leaves the CCD area confined by the corresponding microcylinder. The measurement of a wavefront from a progressive addition lens with an 80 lambda peak-to-valley value reveals the capabilities of the sensor. PMID- 17339932 TI - Multiwall carbon nanotube absorber on a thin-film lithium niobate pyroelectric detector. AB - Multiwall carbon nanotubes (MWNTs) were applied in a bulk layer to a pyroelectric film to increase the detector sensitivity nearly fourfold without a substantial penalty to the low-frequency response (4-100 Hz). In addition, the spectral sensitivity over the wavelength range from 600 to 1800 nm was uniformly enhanced, with variations less than 1%. The results demonstrate the suitability of MWNTs as an efficient thermal absorber having low thermal mass. PMID- 17339933 TI - Hardness evaluation with an optical ring light. AB - Evaluation of hardness by interrogating the residual indentation in a static test using a microscope can be hampered by poor image quality. Image digitization with processing may overcome this but is limited by cost, convenience, and speed. It is shown that the indented surface on the sample in a Brinell test acts effectively as a spherical mirror. Thus, placement of an optical ring light coaxial with the microscope objective and at varying distances from the sample surface produces a distinct right light image that can be correspondingly altered in diameter. The Brinell hardness can be computed by determining the ring light to sample distance after adjusting the ring light image diameter to equal the indentation diameter. This approach is verified experimentally and found to be accurate, cost effective, and expeditious. PMID- 17339934 TI - Effective impedance model for analysis of reflection at the interfaces of photonic crystals. AB - We present an alternative definition of impedance to describe the reflection at the interfaces of photonic crystals. We show that this effective impedance can be defined only by the properties of the photonic crystal modes and is independent of the properties of the incident region. This approximate model successfully explains the main features in the reflection spectrum and of various interface terminations of photonic crystals. In particular, we show an impedance matching condition at which reflectionless transmission of power to a low-group-velocity photonic crystal mode is possible, a property that is attractive for various dispersion-based applications of photonic crystals. PMID- 17339935 TI - Fano resonance-based electrically reconfigurable add-drop filters in silicon microring resonator-coupled Mach-Zehnder interferometers. AB - We report a Fano resonance-based electrically reconfigurable add-drop filter using a microring resonator-coupled Mach-Zehnder interferometer (MZI) on a silicon substrate. Our experiments reveal a pair of complementary Fano resonance line shapes that can be electrically tuned and output coupled from the MZI output ports. A near symmetrical resonance peak can be flipped to a near symmetrical resonance dip by applying a forward-bias voltage of less than 1V across a laterally integrated p-i-n diode in the MZI non-resonator-coupled arm. Our scattering-matrix-based modeling shows good agreement with the experiments and indicates ways to enhance the resonance routing functionality. Our work demonstrates the feasibility of an integrated reconfigurable add-drop filter with actively interchangeable throughput and drop ports. PMID- 17339936 TI - Integrated photonic decoder with complementary code processing and balanced detection for two-dimensional optical code division multiple access. AB - We propose a novel integrated photonic decoder for two-dimensional (time spreading, wavelength hopping) optical code division multiple access. The decoder is composed of multiplexers-demultiplexers, variable delay lines, and a coupler, which processes complementary codes and utilizes balanced detection to reduce unwanted cross-correlation interference. We successfully carried out a 10 Gbit/s transmission that demonstrated its effectiveness. PMID- 17339937 TI - Ultracompact waveguide bends with simple topology in two-dimensional photonic crystal slabs for optical communication wavelengths. AB - Ultracompact waveguide bends with simple topology in two-dimensional photonic crystal slabs are proposed by using an annular air groove at the bend corner to improve transmissions of the bends. Analysis indicates that the guided light wave experiences a very slight difference of propagation properties between straight waveguides and bends (with 60 degrees and 120 degrees bending angles). Transmissions of more than 90% can be achieved in the 60 degrees and 120 degrees bends for light waves at 1.55 microm with bandwidths of 101 and 74 nm, respectively. PMID- 17339938 TI - Efficient coherent addition of fiber lasers in free space. AB - An efficient technique in which fiber lasers are coherently added in free space is presented. Since the high power of the combined output light propagates in free space rather than inside, fiber optical damage and deleterious nonlinear effects are substantially reduced. Two different configurations are investigated. One involves conventional intracavity coupling between the lasers. The other is a novel configuration where the coupling is done out of the combined cavities. The latter configuration requires much less coupling for obtaining the same output power, so the damage to the fiber is further reduced. PMID- 17339939 TI - Quantum dot laser with 75 nm broad spectrum of emission. AB - We report on a quantum dot laser having an emission spectrum as broad as 74.9 nm at 25 degrees C in the 1.2-1.28 wavelength interval with a total pulsed output power of 750 mW in single lateral mode regime and the average spectral power density of >10 mW/nm. A significant overlap and approximate equalization of the ground-state and the excited-state emission bands in the laser's spectrum is achieved by means of intentional inhomogeneous broadening of the quantum dot energy levels. PMID- 17339940 TI - Determining the phase-energy coupling coefficient in carrier-envelope phase measurements. AB - For f-to-2f interferometers based on white-light generation in sapphire plates, the accuracy of the carrier-envelope (CE) phase measurement and stabilization is affected by the laser energy fluctuation. The coupling coefficient between the CE phase and the laser energy has been determined by modulating the pulse energy in an in-loop f-to-2f interferometer while measuring the CE phase variation with an out-loop interferometer. When the total spectral phase measured by the in-loop interferometer was locked, a 1% change in laser energy caused a 160 mrad shift in the CE phase of the output pulses. PMID- 17339941 TI - Diode-pumped Nd:YAG laser emitting at 899 nm and below. AB - We present what is, to the best of our knowledge, the first diode-pumped Nd:YAG laser emitting at 899 nm and below, based on the (4)F(3/2) - (4)I(9/2) transition, generally used for a 946 nm emission. A power of 630 mW at 899 nm has been achieved in cw operation and 16 mW at 884 nm with a fiber-coupled laser diode emitting 9 W at 808 nm. Intracavity second-harmonic generation in cw mode has also been demonstrated with a power of 100 mW at 450 nm by using a LiB(3)O(5) nonlinear crystal. PMID- 17339942 TI - Low-noise 62 W CW intracavity-doubled TEM00 Nd:YVO4 green laser pumped at 888 nm. AB - We present a CW intracavity frequency-doubled TEM(00) Nd:YVO(4) laser oscillator pumped at 888 nm, producing 62W of green light at 532 nm with M(2)=1.05 and RMS noise of 0.05%, thanks to the simultaneous oscillation of a large number of longitudinal modes. A diode-to-green optical efficiency of 29% is achieved by the use of a noncritically phase-matched lithium triborate crystal inserted in a periodic resonator containing two Nd:YVO(4) crystals pumped with a total of 211W at 888 nm. PMID- 17339943 TI - First-order distributed feedback dye laser effect in reflection pumping geometry. AB - Tunable distributed feedback lasing output based on reflection grating configuration instead of the traditional transmission one was realized from rhodamine 6G (R6G)-doped ethanol and 4-dicyanomethylene-2-methyl-6- (p dimethylaminostyryl)-4H-pyran-(DCM)-doped methanol. Pure gain coupling and additional index coupling were obtained in R6G-doped ethanol and DCM-doped methanol, respectively. The tuning, which was found to be independent of the refractive index of the lasing media, went through the entire stimulated emission band for the two cases. Dual-peak lasing emission indicative of the existence of an index grating was observed in DCM-doped methanol. The interval between the two peaks increased with pump energy. PMID- 17339944 TI - Frequency-modulated stimulated Brillouin spectroscopy in LiTaO3. AB - By using a high-precision FM Brillouin spectrometer with the spectral resolution of 20 kHz, we have succeeded in determining the Brillouin linewidth of single crystal LiTaO(3). The large directional anisotropy for the attenuation rate of the longitudinal elastic wave and the extremely narrow Brillouin linewidth of 1.60 MHz have been observed at room temperature. PMID- 17339945 TI - Fresnel particle tracing in three dimensions using diffraction phase microscopy. AB - We have developed a novel experimental technique for tracking small particles in three dimensions with nanometer accuracy. The longitudinal positioning of a micrometer-sized particle is determined by using the Fresnel approximation to describe the transverse distribution of the wavefront that originated in the particle. The method utilizes the high-sensitivity quantitative phase imaging capability of diffraction phase microscopy recently developed in our laboratory. We demonstrate the principle of the technique with experiments on Brownian particles jittering in water both in bulk and in the vicinity of a boundary. The particles are localized in space within an error cube of 20 nm x 20 nm x 20 nm for a 33 Hz acquisition rate and 20s recording time. PMID- 17339946 TI - Solid-state Raman laser generating discretely tunable ultraviolet between 266 and 320 nm. AB - We report a KGd(WO(4))(2) Raman laser pumped by a 532 nm laser that uses the intracavity nonlinear second harmonic and sum-frequency mixing of the Stokes and fundamental fields in beta-barium borate to generate selectable output among eight output wavelengths over the range 266-320 nm. Output pulse energies of up to 0.22 mJ at 10 Hz pulse repetition rate and average output powers up to 48 mW at 5 kHz were achieved. PMID- 17339947 TI - Observation of ultrabroadband, beamlike parametric downconversion. AB - We report spontaneous parametric downconversion having an unusually wide spectral bandwidth. A collinear type 1 phase-matching configuration is employed with degeneracy near the zero group-velocity dispersion frequency. With a spectral width of 1080 nm and degenerate wavelength of 1885 nm, the source also emits a high flux of 3.4 x 10(11) s(-1)W(-1) photon pairs constrained to a cone of only approximately 2 degrees half-angle. A rigorous theoretical approach is developed that confirms the experimental observations. The source properties are consistent with an ultrashort photon-pair correlation time and, for a narrowband pump, extremely high-dimensional spectral entanglement. PMID- 17339948 TI - Elliptic X-shaped light bullets. AB - Elliptic X-shaped light bullets, which are generated as nondiffraction elliptic Bessel-like beams with central humps of elliptical shape during the propagation of asymmetric input ultrashort pulses in normal dispersive quadratic media, are demonstrated to be quite stable against wave-packet breakup due to asymmetric input or anisotropic diffraction. Walking elliptic X-shaped light bullets can be observed without spatial wave-packet breakup for strongly coupled fundamental wave and second-harmonic ultrashort pulses with nonvanishing group-velocity mismatch. PMID- 17339949 TI - Tamm oscillations in semi-infinite nonlinear waveguide arrays. AB - We demonstrate the existence of nonlinear Tamm oscillations at the interface between a substrate and a one-dimensional waveguide array with either cubic or saturable, self-focusing or self-defocusing nonlinearity. Light is trapped in the vicinity of the array boundary due to the interplay between the repulsive edge potential and Bragg reflection inside the array. In the special case when this potential is linear these oscillations reduce themselves to surface Bloch oscillations. PMID- 17339950 TI - Enhanced second-harmonic generation in AlGaAs microring resonators. AB - Highly efficient second-harmonic generation can be achieved by harnessing resonance effects in microring resonator structures. We propose an angular quasi phase-matching scheme based on the position dependence of polarization inside the ring resonator. PMID- 17339951 TI - Self-pumped phase conjugation in a liquid crystal light valve with a tilted feedback mirror. AB - We report self-pumped phase conjugation in a photorefractive liquid crystal light valve with a tilted feedback mirror. This is a new scheme for the self-generation of a phase-conjugate replica and can in general be applied to thin nonlinear layers, opening the way to distortion-correction applications of thin media. PMID- 17339952 TI - Creating second-order nonlinearity in pure synthetic silica optical fibers by thermal poling. AB - A twin-hole optical fiber with pure synthetic silicate glass between the two electrode holes was thermally poled. The induced second-order nonlinearity (SON) was located at the core-cladding interface sections that were nearly parallel to the poling electric field. The polarization dependence of the induced SON suggests that nonlinearity was due to the presence of a space-charge field, which was probably formed by electron migration among the defects located at the core cladding interface. The magnitude of the induced SON was measured to be approximately 0.06 pm /V. PMID- 17339953 TI - All-optical demultiplexing of 640 to 40 Gbits/s using filtered chirp of a semiconductor optical amplifier. AB - We present a high-capacity ultrafast all-optical time demultiplexer that can be employed to retrieve 40 gigabits/second (Gb/s) base-rate channels from a 640 Gb/s single-polarized signal. The demultiplexer utilizes ultrafast effects of filtered chirp of a semiconductor optical amplifier. Excellent demultiplexing performance is shown at very low switching powers: +8 dBm (640 Gb/s data) and -14 dBm (40 GHz clock). The demultiplexer has a simple structure and, in principle, allows monolithic integration. PMID- 17339954 TI - Spin-induced angular momentum switching. AB - When light is transmitted through optically inhomogeneous and anisotropic media the spatial distribution of light can be modified according to its input polarization state. A complete analysis of this process, based on the paraxial approximation, is presented, and we show how it can be exploited to produce a spin-controlled change in the orbital angular momentum of light beams propagating in patterned space-variant optical axis phase plates. We also unveil a new effect: the development of a strong modulation in the angular momentum change upon variation of the optical path through the phase plates. PMID- 17339955 TI - All-fiber acousto-optic polarization monitor. AB - We describe the operational principle of and experimentally demonstrate a narrowband, wavelength-tunable polarization monitor based on a fiber acousto optic tunable filter. Two orthogonally vibrating acoustic waves are used to create a variable polarizer that can be used to measure the state of polarization of an incident narrowband light source. The accuracy of the polarization monitor is measured at two different wavelengths in reference to a commercial polarimeter and is shown to be within 5%. PMID- 17339956 TI - Tailoring the depth of focus for optical imaging systems using a Fourier transform approach. AB - We show how to tailor the depth of focus for an optical system using pupil functions obtained from a Fourier transform approach. These complex amplitude and phase pupil functions are encoded onto a single liquid-crystal spatial light modulator. Experimental results show excellent agreement with theory and indicate the power of this approach. PMID- 17339957 TI - Polychromatic vectorial vortex formed by geometric phase elements. AB - We propose the use of a geometric phase, obtained by spatial polarization state manipulations, for the formation of polychromatic vectorial vortices. Experimental demonstration is obtained by using Pancharatnam-Berry phase optical elements formed by a space-variant subwavelength grating etched on a GaAs wafer. We further demonstrate formation of scalar and unpolarized polychromatic vortices. PMID- 17339958 TI - Study of the field emitted by a source placed inside a two-dimensional left handed metamaterial. AB - We studied the properties of electromagnetic waves that were emitted from a source placed inside a left-handed medium based on a two-dimensional labyrinth. While the arguments of geometrical optics suggest that the field emitted from the source would be focused outside the left-handed medium no matter where the source was placed, our results proved the contrary. We found that the field emitted from the source was focused outside the left-handed medium when the source was placed inside the medium at a certain distance away from the interface. Moreover, our results showed that the field emitted from the source was focused on the subwavelength dimensions outside the left-handed medium. PMID- 17339959 TI - Broadband focused waves with compensated spatial dispersion: transverse versus axial balance. AB - We determine the constraints an ABCD optical system must verify to achieve, at the focal region, broadband waves with compensated spatial dispersion either along the optical axis, called on-axis isodiffracting fields, or in the lateral direction, here named in-plane isodiffracting beams. An optical configuration is identified for generating both types of achromatic broadband focused wave fields. An experimental verification is also provided. PMID- 17339960 TI - Circular dichroism of planar chiral magnetic metamaterials. AB - We propose, fabricate, and study a double-layer chiral planar metamaterial that exhibits pronounced circular dichroism at near-infrared wavelengths. The antisymmetric oscillation modes of the two coupled layers allow local magnetic dipole moments and enhanced polarization effects compared with similar single layer systems where only electric-dipole moments occur. Experiment and rigorous theoretical calculations are in good agreement. PMID- 17339961 TI - Piezospectroscopic imaging with a tunable Fabry-Perot filter and Tikhonov reconstruction. AB - By combining two well-established techniques--multispectral imaging with a tunable filter and regularized data inversion--a fast and accurate method for measuring, at each pixel of a CCD array, the spectrum emitted by a radiating object is obtained. The method is demonstrated with ruby R(1)- and R(2)-line fluorescence, using a narrowband tilt-tunable Fabry-Perot interference filter for data acquisition. Since the data inversion problem is badly ill conditioned, regularization is essential to obtain meaningful results. The reconstruction is capable of a peak wavelength accuracy of 0.01 nm, sufficient to measure the small wavelength shifts encountered in rubylike materials due to changes in the local crystal lattice stress. Thus, the technique presents a novel approach to piezospectroscopic imaging and offers 2 to 3 orders of magnitude faster mapping of local stress than current techniques. PMID- 17339962 TI - Complex refractive index of turbid liquids. AB - We present a multifunction spectrophotometer for the measurement of light reflection from thick and transmission from very thin turbid liquid samples. Moreover, we present a method to get the complex refractive index of such turbid liquids. As an example of the high performance of the device and the method, we present data on inks that are used in offset printing. PMID- 17339963 TI - 32 Phase X 32 amplitude optical arbitrary waveform generation. AB - We describe the precise shaping and mode-resolved amplitude and phase characterization of optical arbitrary waveforms by using a 20 GHz optical frequency comb and integrated 64 x 20 GHz channel arrayed waveguide grating pair. Complex waveforms with large variations in phase and amplitude between adjacent modes were generated and characterized. PMID- 17339964 TI - Intense self-compressed, self-phase-stabilized few-cycle pulses at 2 microm from an optical filament. AB - We report the compression of intense, carrier-envelope phase stable mid-IR pulses down to few-cycle duration using an optical filament. A filament in xenon gas is formed by using self-phase stabilized 330 microJ 55 fs pulses at 2 microm produced via difference-frequency generation in a Ti:sapphire-pumped optical parametric amplifier. The ultrabroadband 2 microm carrier-wavelength output is self-compressed below 3 optical cycles and has a 270 microJ pulse energy. The self-locked phase offset of the 2 microm difference-frequency field is preserved after filamentation. This is to our knowledge the first experimental realization of pulse compression in optical filaments at mid-IR wavelengths (lambda>0.8 microm). PMID- 17339965 TI - Divided-pulse amplification of ultrashort pulses. AB - We propose and demonstrate a new approach, to the best of our knowledge, for avoiding nonlinear effects in the amplification of ultrashort optical pulses. The initial pulse is divided longitudinally into a sequence of lower-energy pulses that are otherwise identical to the original, except for the polarization. The low-intensity pulses are amplified and then recombined to create a final intense pulse. This divided-pulse amplification complements techniques based on dispersion management. PMID- 17339966 TI - Polarization-insensitive ultralow-power second-harmonic generation frequency resolved optical gating. AB - We demonstrate polarization-insensitive ultralow-power second-harmonic generation frequency-resolved optical gating (FROG) measurements with a fiber-pigtailed, aperiodically poled lithium niobate waveguide. By scrambling the polarization much faster than the measurement integration time, we eliminate the impairment that frequency-independent random polarization fluctuations induce in FROG measurements. As a result we are able to retrieve intensity and phase profiles of few hundred femtosecond optical pulses with 50 MHz repetition rates at 5.2 nW coupled average power without control of the input polarization. PMID- 17339968 TI - Gynaecological cancer in Australian general practice. AB - Gynaecological cancer is not commonly managed in general practice with only 454 occurrences of the problem in the 8 year period of the BEACH study; or 1 per 1000 encounters with female patients. This represents an average of 57 327 encounters at which gynaecological cancers were managed in general practice across Australia in any 1 year. PMID- 17339967 TI - The Kuleshov Effect: the influence of contextual framing on emotional attributions. AB - Filmmakers have long recognized the importance of editing techniques to guide the audiences' perceptions and enhance the impact of a scene. We demonstrate behaviorally that pairing identical faces with either neutral or emotionally salient contextual movies, an editing technique referred to as the 'Kuleshov Effect', results in both altered attributions of facial expression and mental state. Using functional neuroimaging (fMRI), we show that faces paired with emotional movies enhance BOLD responses in the bilateral temporal pole, anterior cingulate cortices, amygdala and bilateral superior temporal sulcus relative to identical faces juxtaposed with neutral movies. An interaction was observed in the right amygdala when subtle happy and fear faces were juxtaposed with positive and negative movies, respectively. An interaction between happy faces and negative context was also observed in bilateral amygdala suggesting that the amygdala may act to prime or tag affective value to faces. A parametric modulation of BOLD signal by attribution ratings indicated a dissociation between ventrolateral and the ventromedial prefrontal cortex for negative and positive contextually evoked attributions, respectively. These prefrontal regions may act to guide appropriate choices across altering contexts. Together, these findings offer a neurobiological basis for contextual framing effects on social attributions. PMID- 17339969 TI - HPV vaccination - a paradigm shift in public health. AB - BACKGROUND: In 2006, the world's first quadrivalent human papillomavirus (HPV) vaccine (Gardasil) was made available to the Australian public. The quadrivalent HPV vaccine protects against cervical cancer, cervical abnormalities, and genital warts related to HPV types 6, 11, 16 and 18. General practitioners play a vital role in preventive medicine and as such should have a good understanding of the vaccine and its role in the primary prevention of cervical cancer and precancers. OBJECTIVE: This article provides an overview of the HPV vaccine including efficacy and safety as it relates to its approved use in Australia. DISCUSSION: The vaccine (Gardasil) is quadrivalent, providing protection against HPV types 6, 11, 16 and 18. These HPV types represent a significant burden on public health as they are responsible for 70% of cervical cancers, a substantial proportion of cervical abnormalities, and 90% of genital warts. The quadrivalent HPV vaccine (Gardasil) is indicated for females aged 9-26 years and males aged 9-15 years and should ideally be administered before the onset of sexual activity, however sexually active patients will also benefit. PMID- 17339970 TI - Pap test update. AB - BACKGROUND: 2006 was an eventful year in the area of screening to prevent cervical cancer. New screening guidelines were introduced nationally in July, and in November the Australian Government agreed to fund one of the human papillomavirus (HPV) vaccines, Gardasil, under the National Immunisation Program. OBJECTIVE: This article discusses the cervical screening program and the Pap test in the era of HPV vaccination. DISCUSSION: With the introduction of a vaccine to prevent the acquisition of significant genital HPV types, many practitioners will be questioning the continuing need for the Pap test. But for those women who have missed out on the vaccine, the Pap test will still play a crucial role in preventing the development of cervical cancer, and the vaccinated cohort will need to continue screening in some form as the vaccine does not cover all the HPV types responsible for anogenital cancer. PMID- 17339971 TI - The woman with postmenopausal bleeding. AB - BACKGROUND: Postmenopausal bleeding is a common complaint from women seen in general practice. OBJECTIVE: This article outlines a general approach to such patients and discusses the diagnostic possibilities and their management. DISCUSSION: The most common cause of postmenopausal bleeding is atrophic vaginitis or endometritis. However, as 10% of women with postmenopausal bleeding will be found to have endometrial cancer, all patients must be properly assessed to rule out the diagnosis of malignancy. Most women with endometrial cancer will be diagnosed with early stage disease when the prognosis is excellent as postmenopausal bleeding is an early warning sign that leads women to seek medical advice. PMID- 17339972 TI - Management of cervical cancer. AB - BACKGROUND: Australia now has one of the lowest incidence and mortality rates for cervical cancer worldwide. Women who develop the disease frequently have underutilised cervical screening opportunities and commonly present with symptoms such as abnormal vaginal bleeding. OBJECTIVE: This article reviews the management of women presenting with cervical cancer in Australia today. DISCUSSION: Although fertility sparing options of management are emerging, these options are only available for women presenting with early stage disease. For women presenting with substantial disease, radical surgery and/or chemoradiation is required. These women face the rigors of radical therapy as well as challenges to their sexual identity with loss of fertility, loss of ovarian function, and vaginal shortening and stenosis. Health care providers need to be cognitive and sensitive to these issues. PMID- 17339973 TI - Ovarian cancer screening. AB - BACKGROUND: Current tests used in the diagnosis of ovarian cancer are the CA-125 blood test and transvaginal ultrasound. OBJECTIVE: This article discusses the available evidence and recommendations for ovarian cancer screening in both the general population, and in at risk women. DISCUSSION: General population screening is not recommended, however there is a large, randomised controlled trial currently underway investigating this. There is no data to support the effectiveness of screening in high risk women (carriers of BRCA1 or BRCA2 mutations, or carriers of mismatch repair gene mutations in the hereditary nonpolyposis colorectal cancer group) as most tumours detected by screening are at an advanced stage at diagnosis. Prophylactic surgery to remove the fallopian tubes and ovaries is recommended after the completion of childbearing to prevent 90% of ovarian cancers in these women. The remaining 10% of these tumours arise in the peritoneal cavity as primary peritoneal cancers and behave in a similar way to ovarian cancers, and, by definition, are advanced at diagnosis. The future holds hope of new screening tests becoming available. PMID- 17339974 TI - Ovarian cancer - diagnosis and management. AB - BACKGROUND: Epithelial ovarian cancer presents most often as late stage disease due to a lack of effective screening tests and vagueness of symptoms. OBJECTIVE: This article outlines the diagnosis and management of ovarian cancer. DISCUSSION: Women with suspected ovarian cancer are best managed in a gynaecological treatment unit offering multidisciplinary care. Surgery is usually needed both to make a diagnosis and for definitive treatment and referral to a specialty trained gynaecological oncologist is appropriate. Most women will also require chemotherapy. Ovarian cancers have good sensitivity to several drugs but relapse rates are high. This means that ovarian cancer is now seen as a chronic disease with often several episodes of remission, relapse and treatment. The psychological impact of this diagnosis both on the woman and her family are significant and best dealt with proactively. PMID- 17339975 TI - Integrative medicine in gynaecological cancers. AB - Gynaecological cancers are the fifth most common cause of cancer death in women in Australia. This article reviews three studies investigating nutritional aspects relating to gynaecological cancers. PMID- 17339976 TI - Prevention of progression of kidney disease: diabetic nephropathy - CARI guidelines. AB - The Caring for Australasians with Renal Impairment (CARI) guidelines initiative is an Australian and New Zealand project that aims to provide high quality, evidence based clinical practice guidelines for the management of all stages of kidney disease. This article summarises CARI guidelines on the Prevention of progression of kidney disease: diabetic nephropathy. PMID- 17339977 TI - Rare skin cancers in general practice. AB - Mr LA has long been troubled with actinic damage to his skin, especially his face. He has had many squamous cell carcinomas (SCCs) removed and many solar keratoses managed. On this occasion Mr LA had two actinic lesions on his left cheek that failed to respond to cryotherapy. A biopsy of each site produced a surprise. Histology of the superior lesion revealed sebaceous carcinoma. This is an uncommon yet aggressive cutaneous malignancy derived from sebaceous glands. The 5 year survival rate is 60-70%. The tumour was widely excised with a minimum 10 mm margin. A multidisciplinary approach resulted in a decision not to proceed to adjunctive radiotherapy. The wound was well healed by 8 weeks. Four years on there is no sign of local or regional recurrence. PMID- 17339978 TI - Clinical breast examination for asymptomatic women - exploring the evidence. AB - BACKGROUND: Clinical breast examination (CBE) is often offered as a component of the well woman check or carried out at the request of an asymptomatic woman. In these cases the examination is a screening procedure, as opposed to a diagnostic CBE in a symptomatic woman. OBJECTIVE: This article examines the evidence for screening CBE. DISCUSSION: Screening CBE should involve informed consent. A negative examination does not exclude the presence of breast cancer and women should be aware of this. There have been no randomised controlled trials of CBE alone, only trials comparing CBE with mammography for the detection of breast cancer. While there is a low sensitivity (54%) for CBE, the specificity is high (94%). It is unlikely that these figures are discussed with patients. There are different methods of CBE, and these are described in the literature without a firm evidence base as to effectiveness. However, evidence does suggest that practice on models and retraining help improve clinicians' skills. PMID- 17339979 TI - Health care of refugee women. AB - BACKGROUND: Women refugees have endured major discrimination and poverty in their countries of origin or countries of displacement. This has had a major impact on their physical and psychological health. The experience of resettlement places a further burden on their health. OBJECTIVE: This article aims to provide a simple approach to the health assessment and management of women refugees, taking into account specific issues related to migration and resettlement. DISCUSSION: Because of the complexities of their realities related to gender, social and economic status, and premigration and resettlement experiences, women refugees need a multiplicity of health interventions. The identification of the major physical and psychological health issues with consideration of gender issues and premigration and resettlement experiences, represents more adequate basis for the assessment and management of the health care of women refugees. PMID- 17339980 TI - Extending care to women lay carers. AB - Women represent 71% of the 474,600 primary lay carers in Australia. It is well documented that providing care for family members with a life threatening illness places a strain on the health and emotional wellbeing of the carer. Lay carers are rarely attentive to their own health needs due to lack of time and energy, and owing to feelings of guilt, they are unlikely to seek medial attention for preventive health concerns. This article presents four case studies that illustrate the tragic consequences of delayed review for self detected breast lumps which were proven to be breast cancer. PMID- 17339981 TI - Children and adolescents - who can give consent? AB - Case histories are based on actual medical negligence claims or medicolegal referrals; however certain facts have been omitted or changed by the author to ensure the anonymity of the parties involved. Can children and adolescents consent to their own medical treatment? Do general practitioners owe teenagers a duty of confidentiality? This article examines the legal obligations of GPs when obtaining consent to medical treatment from patients who are under 18 years of age. PMID- 17339982 TI - From solo practice to partnering - the evolution of the Elmore Model of Primary Health. AB - The Elmore Primary Health Service is located in Elmore, 46 km northeast of Bendigo in central Victoria. The population of the town and surrounding district is approximately 5400. Elmore was formerly a campus of the Rochester and Elmore District Health Service until a service review enabled the development of a new model that brought together the local general practice and a community health service as partners. PMID- 17339983 TI - Systems and complexity thinking in general practice: part 1 - clinical application. AB - Many problems encountered in general practice cannot be sufficiently explained within the Newtonian reductionist paradigm. Systems and complexity thinking - already widely adopted in most nonmedical disciplines - describes and explores the contextual nature of questions posed in medicine, and in general practice in particular. This article briefly describes the framework underpinning systems and complexity sciences. A case study illustrates how systems and complexity thinking can help to better understand the contextual nature of patient presentations, and how different approaches will lead to different outcomes. PMID- 17339984 TI - Talking with patients from Howlong to the Himalayas - do all our patients want us to be patient centred? AB - Patient centred communication is an important feature of general practice training. It is cited by general practitioners as one of the defining features of our specialty. However, many doctors are not convinced that this approach is always suitable. This article highlights the range of expectations that patients have toward communication styles. The experience of researching this topic in Nepal has confirmed this diversity for me. We need to have various communication styles at our disposal so that we can engage as many of our patients as possible. PMID- 17339985 TI - Is there a GP in the hospital? AB - Modern health care is increasingly complex with a progression to specialisation and super specialisation in the primary and tertiary settings. Traditional models of health such as the biomedical model are often inadequate. The value of a more holistic approach to patients' health problems has been long accepted by the medical profession. As health care becomes more fragmented we are overlooking the potential benefits of a generalist approach in improving the care of patients in our hospitals. This article examines the potential benefits of involving general practitioners in the tertiary care setting. PMID- 17339986 TI - Children with a regular FP - do they have better health behaviours and psychosocial health? AB - BACKGROUND: Adults who receive care from family physicians (FPs) are healthier than those who do not, but not much is known about the health behaviours and psychosocial health of children who have FPs. OBJECTIVE: This study aims to test the hypothesis that children who have a regular FP have better health behaviours and psychosocial health than children who do not have a regular FP. METHODS: The health behaviours and psychosocial wellbeing of 7057 children in Hong Kong were measured by the Youth Risk Behaviour Survey and the 'anxious/depressed', 'somatic complaints' and 'aggressive behaviours' domains of the Children Behaviour Checklist (CBCL). RESULTS: Good health and hygiene behaviours were significantly more prevalent in children who had a regular FP. Children who did not have a regular FP had statistically significant higher scores in all three main domains of the CBCL. Children with a regular FP had higher odds ratios for various hygiene and health behaviours after adjusting for socioeconomic status. DISCUSSION: The findings highlight the potential role of FPs in promoting health, hygiene, and wellbeing in children. PMID- 17339987 TI - Cervical screening in general practice - strategies for improving participation. AB - BACKGROUND: National cervical screening rates have plateaued at around 60%. Each method of recruitment has an upper limit to uptake and the benefits of multiple strategies are additive. There is debate about reallocating Pap testing to nurses in general practice. OBJECTIVE: To assess the effects on cervical screening rates in one small general practice. METHODS: An audit of the effect of: updating Pap test details in electronic records; active recruitment by letter; follow up telephone call if no appointment made; altering the letter to invite women to separate themselves into Pap test 'plus other issues' or 'screening test only'; and the offer of a Pap test for the 'Pap test only' group to be performed by a nurse. RESULTS: Over 18 months there was a 27% improvement from a biannual screening rate of 53% at baseline to 67.5% at the end of the audit. Over the past 6 months, 49% of women elected for the 'screening only' test provided by a nurse. DISCUSSION: All four strategies are feasible and associated with a considerable increase in screening rates. Patients can choose to have their test performed by a nurse in general practice. This study suggests that each strategy's improvement in uptake is independently additive. PMID- 17339988 TI - General practice consultations - how well do doctors predict patient satisfaction? AB - BACKGROUND: While patient satisfaction with the general practice consultation has been extensively researched, there have been relatively few studies of doctors' perception of patient satisfaction. This study sought to measure how accurately doctors are able to predict patient satisfaction with consultations in general practice. METHODS: Adult patients consulting about new episodes of illness in general practice completed a consultation satisfaction questionnaire. The scores from the questionnaire were compared with doctors' predictions of patient satisfaction. RESULTS: Nine general practitioners completed the study and returned a total of 167 pairs of questionnaires. On average, the patients gave their doctors higher scores on the general satisfaction and professional care scales than on the depth of relationship and perceived time scales of the questionnaire. On every scale, patients reported higher levels of satisfaction than their doctors predicted they would. There was poor correlation between patient and doctor scores for the perceived time scale, but moderate correlation for the other three scales. DISCUSSION: Our findings suggest that a doctor's sense that a patient was not satisfied following a consultation may be valid, but that doctors may underestimate their patients' satisfaction. PMID- 17339989 TI - Is your sample cupboard relevant to your practice? AB - Sample medications represented 4% (3.8 million Australian dollars) of the Australian general practice promotional budget of pharmaceutical companies in the second quarter of 2005. In the United States, general practitioners have been shown to use sample medication in up to 20% of encounters both for commencing and for full treatment. Given the USA does not have a universal subsidy for medications like Australia, sample use may be higher than Australian GPs operating with the Pharmaceutical Benefits Scheme. Australian GPs perceive benefits for samples as a trial run: to test patient tolerability, enhance patient satisfaction, and for those who cannot afford multiple trials of drugs. Acceptance of samples by GPs is associated with preference for and rapid prescription of new drugs and positive attitudes toward pharmaceutical representatives. Concerns with sample medications include prescribing medication that is not the GP's preferred choice owing to the limited range of samples available. Other concerns include dispensing expired medication and wastage of medications. PMID- 17339990 TI - GPs, violence and work performance - 'just part of the job?'. AB - BACKGROUND: This study explored the impact of work related violence on general practitioners' work performance. METHOD: A postal survey of 1000 randomly selected GPs about work related violence. Those GPs reporting incidents of work related violence in the past 12 months were asked to write about its effect on them in response to an open question. RESULTS: Eighty-five GPs responded. Seventy three percent of GPs who had experienced work related violence answered an open question about its effect on their work performance. The effect was negative for most, respondents citing poor concentration, difficulty listening to patients, rumination and intrusive thoughts when in an enclosed space in subsequent consultations, particularly in consultations with the patient who had perpetrated the violence, or their families or coworkers, or with similar patients. DISCUSSION: General practitioners have reported that work related violence has a continuing impact on their work performance. Future research should include psychometric testing of cognitive functioning and mental health testing to quantify this. PMID- 17339991 TI - Organometallic manganese complexes as scaffolds for potential molecular wires. AB - This article reviews recent work in the area of organomanganese chemistry designing organometallic based molecular wires for potential applications in molecular electronics utilising the bottom-up approach. The field of molecular electronics has recently received much attention in the pursuit of continued miniaturization of electronics. Molecular wires that can allow a through-bridge exchange of an electron/electron hole between its remote ends/terminal groups are the basic motifs of single electron devices. Our recent work in this field has been the design and development of transition-metal complexes with a special emphasis on the half sandwich dinuclear manganese complexes and the bis dmpe dinuclear Mn(II)/Mn(II). In this review, we would like to highlight the importance of the nature of the transition metal and their significant effect on the redox process, which is of paramount importance for the design of systems that could be ultimately wired into circuits for various applications. PMID- 17339992 TI - Cyclometalation vs. Werner-type coordination of sterically enforced palladium(II) 1,3-bis(pyridyl-2-imino)isoindolines (Pd-BPIs). AB - The reaction of 1,3-bis(4,6-dimethylpyridyl-2-imino)isoindoline and palladium acetate in methanol selectively yields the expected acetato palladium N,N,N chelate or a cyclometalated tetranuclear dimer depending on the stoichiometry of the reactants. PMID- 17339993 TI - On the mechanism of the Rh(II)-catalysed cyclopropanation of alkenes. AB - The mechanism of Rh(ii)-catalysed cyclopropanation has been investigated computationally using Rh(2)(formate)(4) as a model precatalyst, with the model organic substrates CH(2)N(2) and C(2)H(4) and MeCl as a model for coordinating solvent. Three potential carriers of catalysis have been identified, one retaining the Rh(2)(formate)(4) framework and two others resulting from ligand insertion of Rh-CH(2) into an Rh-O bond. Both 2 + 1 and 2 + 2 pathways have been identified for the cyclopropanation step depending on the catalytic carrier involved. Complexes resulting from CH(2) insertion into the Rh-O bond are more efficient at lowering the activation enthalpy for CH(2)-N(2) scission in the rate determining step. PMID- 17339994 TI - Crystal structure and dynamic properties of a bimetallic cyano complex Cd(C4H8O2)Cu(CN)3 with an interpenetrating 3D framework containing a 1,4-dioxane bridging ligand as a rotor. AB - The title complex Cd(C(4)H(8)O(2))Cu(CN)(3) has a 3D twofold interpenetrating framework structure. The structural base of the framework is a planar hexagonal network complex of [Cu(CN)(3)Cd](infinity) ,which is formed with cyanides connecting the coordination sites of Cu(i) ions with a triangle planar form and the equatorial coordination sites of Cd(ii) ions with a trigonal bipyramid form. The networks are stacked and a 1,4-dioxane molecule coordinates to two Cd(ii) ions in alternate networks as a bridging ligand. The 1,4-dioxane ligand penetrates a hexagonal window of the network sandwiched between the bridged networks. This 1,4-dioxane bridge completes the 3D twofold interpenetrating framework structure. (2)H-NMR powder patterns of the deuterated complex Cd(C(4)D(8)O(2))Cu(CN)(3) revealed the dynamics of the 1,4-dioxane bridge as a rotor. Above 253 K, the 1,4-dioxane ligand undergoes rotational motion combined with a ring inversion between two chair conformations. The free energy of activation DeltaG(double dagger) for the ring inversion was calculated to be 41.4(7) kJ mol(-1) at 298 K. PMID- 17339995 TI - Ligand effects on Ni(II)-catalysed alkane-hydroxylation with m-CPBA. AB - Nickel(ii) complexes supported by a series of pyridylalkylamine ligands [tris(2 pyridylmethyl)amine (TPA; complexes and ), tris[2-(2-pyridyl)ethyl]amine (TEPA; complexes and ), 6-[N,N-bis(2-pyridylmethyl)aminomethyl]-2,4-di-tert-butylphenol ((Dtbp)Pym2H; complexes and ), 6-[N,N-bis[2-(2-pyridyl)ethyl]aminomethyl]-2,4-di tert-butylphenol ((Dtbp)Pye2H; complexes and ), N-benzyl-bis(2 pyridylmethyl)amine ((Bz)Pym2; complex ) and N-benzyl-bis[2-(2 pyridyl)ethyl]amine ((Bz)Pye2; complex )] have been synthesized and structurally characterized by X-ray crystallographic analysis [coordinating counter anion (co ligand) of complexes n (n = 1-6) is AcO(-) and that of complexes n (n = 1-4) is NO(3)(-)]. All complexes, except , were obtained as a mononuclear nickel(ii) complex exhibiting a distorted octahedral geometry, whereas complex was isolated as a dinuclear nickel(ii) complex bridged by two nitrate anions. Catalytic activity of the nickel(ii) complexes were examined in the oxidation of cyclohexane with m-CPBA as an oxidant. In all cases, the oxygenation reaction proceeded catalytically to give cyclohexanol as the major product together with cyclohexanone as the minor product. The complexes containing the pyridylmethylamine (Pym) metal-binding group (, , ) showed higher turnover number (TON) than those containing the pyridylethylamine (Pye) metal-binding group (, , ), whereas the alcohol/ketone (A/K) selectivity was much higher with the latter (Pye system) than the former (Pym system). On the other hand, the existence of the NO(3)(-) co-ligand (, and ) caused a lag phase in the early stage of the catalytic reaction. Electronic and steric effects of the supporting ligands as well as the chemical behavior of the co-ligands on the catalytic activity of the nickel(ii) complexes have been discussed on the basis of their X-ray structures. PMID- 17339996 TI - A stepwise approach to the formation of heterometallic discrete complexes and infinite architectures. AB - A strategy for the controlled construction of heterobimetallic discrete complexes and 1-D coordination networks is presented. The organic ligand based on the methanedithiolate group and the 4,5-diazafluorene moiety behaving as primary and secondary coordination poles respectively leads to the formation of a series of discrete metal complexes with various geometries via binding through the dithiolate site. The observed coordination geometries range from square-planar for Ni(ii) and Pd(ii) to distorted tetrahedral for Zn(ii) and Hg(ii). The square planar Pd(ii) complex affords a discrete bimetallic trinuclear complex when treated with a capped Ni(ii) center. All three Ni(ii), Pd(ii) and Hg(ii) discrete complexes have been also shown to behave as metallatectons leading to the generation of infinite networks in the presence of bridging cations such as sodium. PMID- 17339997 TI - Chemical speciation of copper(II) diaminediamide derivative of pentacycloundecane -a potential anti-inflammatory agent. AB - Formation constants of copper(ii), zinc(ii) and calcium(ii) with 3,5 diaminodiamido-4-oxahexacyclododecane (cageL) has been studied by glass electrode potentiometry at 25 degrees C and an ionic strength of 0.15 mol dm(-3). Copper(ii) forms more stable complexes with cageL than zinc(ii) and calcium(ii). Metal ion complexation promotes deprotonation and coordination of the amide nitrogens resulting in overall tetragonal coordination of Cu(2+) suggested by the UV-visible electronic spectra. Speciation calculations using a blood plasma model suggest that zinc(ii) and calcium(ii) are good competitors of copper(ii) in vivo. Bio-distribution experiments using (64)Cu-labelled Cu(ii)-cageL show that about 50% dose of the complex is retained in the body after 24 h. PMID- 17339998 TI - Versatility of 2,6-diacetylpyridine (dap) hydrazones in generating varied molecular architectures: synthesis and structural characterization of a binuclear double helical Zn(II) complex and a Mn(II) coordination polymer. AB - A binuclear complex of Zn(ii) with formula [Zn(dap(A)(2))](2).2.25DMF (.2.25DMF) and a Mn(ii) coordination polymer with formula [Mn(3)(dap(In)(2))(3)(H(2)O)(2).2DMSO](n) (.2DMSO)(n) have been prepared and structurally characterized [dap(A)(2) = dideprotonated form of 2,6 diacetylpyridine bis(anthraniloyl hydrazone); dap(In)(2) = doubly deprotonated form of 2,6-diacetylpyridine bis(isonicotinoyl hydrazone)]. In the Zn(ii) complex the molecular units are double helical, with the Zn(ii) ions in a square pyramidal environment. The Mn(ii) complex on the other hand is a coordination polymer containing two different types of hepta-coordinated Mn(ii) ions, which differ in their axial ligands. The magnetic properties of the Mn(ii) complex, along with those of a double helical pyridine bridged binuclear Ni(ii) complex, earlier synthesized by us, are also reported. The ability of the 2,6 diacetylpyridine bis(aroyl hydrazone) ligands to form double helical complexes is analyzed in terms of the conformational flexibility of the ligands. The differences in the magnetic properties of the micro-N bridged binuclear complexes formed by 1,1 azido N-bridging ligands, and pyridine N-bridging ligands, is analyzed with the help of EHMO calculations. PMID- 17339999 TI - One electron oxidation of chromium N,N-bis(diarylphosphino)amine and bis(diarylphosphino)methane complexes relevant to ethene trimerisation and tetramerisation. AB - Complexes of the type [(diphosphine)Cr(CO)(4)] (diphosphine = Ph(2)PN(iPr)PPh(2), Ar(2)PN(Me)PAr(2) or Ar(2)PCH(2)PAr(2) (Ar = 2-C(6)H(4)(MeO)) have been synthesised. In the solid state, these complexes show tight phosphine bite angles in the range 67.82(4) degrees to 71.52(5) degrees and the nitrogen atom in N,N bis(diarylphophino)amine ligands adopts an almost planar (sp(2)) geometry. All of the complexes are readily oxidised electrochemically or chemically to corresponding Cr(i) species. There is no evidence for coordination of the pendant ether group in derivatives with Ar = 2-MeO-C(6)H(4) in either Cr(0) or Cr(i) species. Treatment of the [(diphosphine)Cr(CO)(4)] complexes with [NO]BF(4) yields [(diphosphine)Cr(NO)(CO)(3)]BF(4). Removal of CO ligands to generate an oligomerisation-active species is not observed with amine oxides but triethyl aluminium is effective in this role, and active catalysts can be produced. The use of weakly coordinating anions seems crucial in achieving oligomerisation catalysis. PMID- 17340001 TI - Asymmetric catalysis for the construction of quaternary carbon centres: nucleophilic addition on ketones and ketimines. AB - There is a growing need in organic synthesis for efficient methodologies for the asymmetric synthesis of quaternary carbon centres. One of the most attractive and straightforward methods focuses on the use of asymmetric catalysis for the addition of various types of nucleophiles on prochiral ketones and ketimines. A view of the literature from this growing area of research will be presented in this review, with an emphasis on the pioneer works and milestones brought by the main players in this field. PMID- 17340002 TI - Concise synthesis of omega-borono-alpha-amino acids. AB - A short protocol for the practical scale synthesis of several omega-borono-alpha amino acids is described via the alkylation of benzophenone glycinimines with various electrophiles. PMID- 17340000 TI - Carbohydrate post-glycosylational modifications. AB - Carbohydrate modification is a common phenomenon in nature. Many carbohydrate modifications such as some epimerization, O-acetylation, O-sulfation, O methylation, N-deacetylation, and N-sulfation, take place after the formation of oligosaccharide or polysaccharide backbones. These modifications can be categorized as carbohydrate post-glycosylational modifications (PGMs). Carbohydrate PGMs further extend the complexity of the structures and the synthesis of carbohydrates and glycoconjugates. They also increase the capacity of the biological regulation that is achieved by finely tuning the structures of carbohydrates. Developing efficient methods to obtain structurally defined naturally occurring oligosaccharides, polysaccharides, and glycoconjugates with carbohydrate PGMs is essential for understanding the biological significance of carbohydrate PGMs. Combined with high-throughput screening methods, synthetic carbohydrates with PGMs are invaluable probes in structure-activity relationship studies. We illustrate here several classes of carbohydrates with PGMs and their applications. Recent progress in chemical, enzymatic, and chemoenzymatic syntheses of these carbohydrates and their derivatives are also presented. PMID- 17340003 TI - N(epsilon)-methanesulfonyl-lysine as a non-hydrolyzable functional surrogate for N(epsilon)-acetyl-lysine. AB - Through parallel studies on peptides containing N(epsilon)-methanesulfonyl-lysine or N(epsilon)-acetyl-lysine, N(epsilon)-methanesulfonyl-lysine as a replacement for N(epsilon)-acetyl-lysine was shown i) not to compromise the binding affinity for a bromodomain, ii) to confer resistance to human HDAC8 and SIRT1 (two distinct protein deacetylases), and iii) to confer only weak inhibition against human HDAC8 and SIRT1. These results suggested N(epsilon)-methanesulfonyl-lysine as a non-hydrolyzable functional surrogate for N(epsilon)-acetyl-lysine. PMID- 17340004 TI - Molecular shape of palytoxin in aqueous solution. AB - Palytoxin, one of the most toxic non-peptide substances, formed an associated dimer of 5 nm length in aqueous solution. PMID- 17340005 TI - Dendritic receptors designed to bind polyanions in both organic and aqueous media. AB - This paper reports the synthesis of dendrons containing a spermine unit at their focal point. The dendritic branching is based on l-lysine building blocks, and has terminal oligo(ethyleneglycol) units on the surface. As a consequence of the solubilising surface groups, these dendrons have high solubility in solvents with widely different polarities (e.g., dichloromethane and water). The protonated spermine unit at the focal point is an effective anion binding fragment and, as such, these dendrons are able to bind to polyanions. This paper demonstrates that polyanions can be bound in both dichloromethane (using a dye solubilisation assay) and in water (competitive ATP binding assay). In organic media the dendritic branching appears to have a pro-active effect on the solubilisation of the dye, with more dye being solubilised by higher generations of dendron. On the other hand, in water the degree of branching has no impact on the anion binding process. We propose that in this case, the spermine unit is effectively solvated by the bulk solvent and the dendritic branching does not need to play an active role in assisting solubility. Dendritic effects on anion binding have therefore been elucidated in different solvents. The dendritic branching plays a pro-active role in providing the anion binding unit with good solubility in apolar solvent media. PMID- 17340006 TI - Synthesis of cyclic bis- and trismelamine derivatives and their complexation properties with barbiturates. AB - Cyclic bis- and trismelamine derivatives were prepared from cyanuric chloride by stepwise substitutions with appropriate amines. The complexation abilities of these melamine derivatives with barbituric acid derivatives were evaluated by UV vis spectroscopy and (1)H NMR. The structure was also confirmed by X-ray crystallography. Both the acyclic and the cyclic bismelamine derivatives formed a 1 : 1 complex via six hydrogen bonds with barbituric acid derivatives. van't Hoff analyses on the complexation of the bismelamines with the barbituric acid derivative revealed that the complexation of the cyclic bismelamine was entropically favored and enthalpically less favored process than those of the acyclic bismelamine. X-Ray crystallographic analysis and (1)H NMR studies revealed that the cyclic trismelamine bound one barbituric acid derivative into the cavity via six hydrogen bonds by two melamine moieties and another barbituric acid via three hydrogen bonds by the residual melamine moiety. PMID- 17340007 TI - Effect of terminal amino acids on the stability and specificity of PNA-DNA hybridisation. AB - The effect of various charged or hydrophobic amino acids on the hybridisation of fully complementary and mismatch PNA-DNA duplexes was investigated via UV melting curve analysis. The results described here show that the thermal stability and binding specificity of PNA probes can be modified by conjugation to amino acids and these effects should be considered in experimental design when conjugating PNA sequences to solubility enhancing groups or cell transport peptides. Where stabilisation of a duplex is important, without there being a corresponding need for specific binding to fully complementary targets, the conjugation of multiple lysine residues to the C-terminus of PNA may be the best probe design. If, however, the key is to obtain maximum discrimination between fully complementary and mismatch targets, a replacement of glutamic acid for lysine as the routine solubility enhancing group is recommended. PMID- 17340008 TI - Step-wise and pre-organization induced synthesis of a crossed alkene-bridged nisin Z DE-ring mimic by ring-closing metathesis. AB - This paper describes two approaches for the synthesis of a crossed alkene-bridged mimic of the thioether ring system of the nisin Z DE-fragment. The first approach comprised the stepwise total synthesis featuring a cross metathesis and a macrolactamization on a solid support followed by a ring-closing metathesis in solution. Via this route the title compound was obtained in an overall yield of 7% (85% on average for 16 reaction steps). In the second approach, the linear precursor peptide was subjected to ring-closing metathesis and the bicyclic peptide with the correct side chain connectivity pattern was obtained in yields up to 95%. The preferred formation of the bicyclic crossed alkene-bridged mimic of the DE-ring suggests a favorable pre-organization of the linear precursor peptide. PMID- 17340009 TI - Synthesis of DOTA-conjugated multivalent cyclic-RGD peptide dendrimers via 1,3 dipolar cycloaddition and their biological evaluation: implications for tumor targeting and tumor imaging purposes. AB - This report describes the design and synthesis of a series of alpha(V)beta(3) integrin-directed monomeric, dimeric and tetrameric cyclo[Arg-Gly-Asp-d-Phe-Lys] dendrimers using "click chemistry". It was found that the unprotected N-epsilon azido derivative of cyclo[Arg-Gly-Asp-d-Phe-Lys] underwent a highly chemoselective conjugation to amino acid-based dendrimers bearing terminal alkynes using a microwave-assisted Cu(I)-catalyzed 1,3-dipolar cycloaddition. The alpha(V)beta(3) binding characteristics of the dendrimers were determined in vitro and their in vivoalpha(V)beta(3) targeting properties were assessed in nude mice with subcutaneously growing human SK-RC-52 tumors. The multivalent RGD dendrimers were found to have enhanced affinity toward the alpha(V)beta(3) integrin receptor as compared to the monomeric derivative as determined in an in vitro binding assay. In case of the DOTA-conjugated (111)In-labeled RGD dendrimers, it was found that the radiolabeled multimeric dendrimers showed specifically enhanced uptake in alpha(V)beta(3) integrin expressing tumors in vivo. These studies showed that the tetrameric RGD-dendrimer had better tumor targeting properties than its dimeric and monomeric congeners. PMID- 17340010 TI - Microwave-assisted four-component, one-pot condensation reaction: an efficient synthesis of annulated pyridines. AB - A one-pot, effective synthesis of pyridines by a modified Krohnke procedure is described. Polysubstituted annulated pyridines were synthesized in high yields by four-component, one-pot cyclocondensation reactions of N-phenacylpyridinium bromide, aromatic aldehydes, acetophenones or cyclic ketones in the presence of ammonium acetate and acetic acid, assisted by microwave irradiation. In this procedure, cyclic ketones with two alpha-CH(2) groups yield annulated pyridines with additional alpha-benzylidene groups, which are derived in situ from double aldol condensation of cyclic ketones with two moles of aromatic aldehydes. PMID- 17340011 TI - Galactose-derived phosphonate analogues as potential inhibitors of phosphatidylinositol biosynthesis in mycobacteria. AB - Galactose-based phosphonate analogues of myo-inositol-1-phosphate and phosphatidylinositol have been synthesized from methyl beta-d-galactopyranoside. Michaelis-Arbuzov reaction of isopropyl diphenyl phosphite or triisopropyl phosphite with a 6-iodo-3,4-isopropylidene galactoside afforded the corresponding phosphonates. Deprotection of the diphenyl phosphonate afforded methyl beta-d galactoside 6-phosphonate, an analogue of myo-inositol-1-phosphate. The diisopropyl esters of the diisopropyl phosphonate were selectively deprotected and the corresponding anion was coupled with 1,2-dipalmitoyl-sn-glycerol using dicyclohexylcarbodiimide. Deprotection afforded a methyl beta-d-galactoside derived analogue of phosphatidylinositol. The galactose-derived analogues of phosphatidylinositol and myo-inositol-1-phosphate were not substrates for mycobacterial mannosyltransferases (at concentrations up to 1 mM) involved in phosphatidylinositol mannoside biosynthesis in a cell-free extract of Mycobacterium smegmatis. The galactose-derived phosphonate analogue of phosphatidylinositol was shown to be an inhibitor at 0.01 mM of PimA mannosyltransferase involved in the synthesis of phosphatidylinositol mannoside from phosphatidylinositol, and a weaker inhibitor of the next mannosyltransferase(s), which catalyzes the mannosylation of phosphatidylinositol mannoside. PMID- 17340012 TI - Synthesis and solvent driven self-aggregation studies of meso-"C-glycoside" porphyrin derivatives. AB - New types of porphyrin derivatives bearing "C-glycoside" moieties, either in 5,10,15,20- or in 5,15-meso-positions, were prepared and fully characterized. The presence of the glycosidic groups imparts to the title macrocycles, besides an amphiphilic character, a clear tendency to form chiral suprastructures upon solvent-driven self-aggregation in different aqueous-organic solvent mixtures. Supra-assembly phenomena, in terms of the size and morphology of the resulting structures, as well as their kinetics of aggregation, were studied by UV-visible, fluorescence, resonance light scattering (RLS), and CD spectroscopy, indicating that the morphology of the aggregates depends strongly on the structure of the porphyrin rings, and on the bulk conditions of aggregation. PMID- 17340013 TI - 1,2,3-Triazoles as peptide bond isosteres: synthesis and biological evaluation of cyclotetrapeptide mimics. AB - Since the discovery of Cu(I)-catalysed click chemistry, the field of peptidomimetics has expanded to include 1,4-connected 1,2,3-triazoles as useful peptide bond isosteres. Here, we report the synthesis of triazole-containing analogues of the naturally occurring tyrosinase inhibitor cyclo-[Pro-Val-Pro-Tyr] and show that the analogues retain enzyme inhibitory activity, demonstrating the effectiveness of a 1,4-connected 1,2,3-triazole as a trans peptide bond isostere. PMID- 17340014 TI - Synthesis, structure and biological activity of nitroxide malonate methanofullerenes. AB - Two nitroxide methanofullerenes was synthesized for the first time, and their structures and biological activities studied. It was shown by X-ray single crystal analysis that the methanofullerene with two nitroxide groups forms a 1 : 2 inclusion complex with chloroform and has a nearly tetrahedral (diamond-like) arrangement of fullerene-fullerene interactions in the crystal. For the first time, it has been found that malonate nitroxide methanofullerene in combination with the known anticancer drug cyclophosphamide (CPA) shows high antitumor activity against leukemia P-388. PMID- 17340015 TI - Systemic treatment of severe atopic eczema: a systematic review. AB - Systemic immunosuppressive agents are recommended for patients with atopic eczema in whom disease activity cannot be controlled adequately with topical treatments. Guidelines do not give clear advice which agents to prefer. We systematically reviewed clinical trials on systemic treatment for severe atopic eczema to provide evidence-based treatment recommendations. Standardized literature search, independent standardized assessment of eligibility and data abstraction was performed by 2 reviewers. Twenty-seven studies totalling 979 patients were included. Eleven studies consistently showed effectiveness of cyclosporine. Cyclosporine is recommended as first option for patients with atopic eczema refractory to conventional treatment. Evidence from randomized controlled trials also exists for interferon-? and azathioprine. Although frequently used in clinical practice, systemic glucocorticosteroids have not been assessed adequately in studies. Mycophenolate mofetile showed effectiveness in 2 small uncontrolled studies. Intravenous immunoglobulins and infliximab are not recommended based on published data. PMID- 17340016 TI - IP10/CXCL10 - CXCR3 interaction: a potential self-recruiting mechanism for cytotoxic lymphocytes in lichen sclerosus et atrophicus. AB - Lichen sclerosus et atrophicus is a chronic inflammatory skin disease of unknown aetiology. Recent studies have indicated that autoimmune mechanisms might be involved in its pathogenesis and have suggested a role for autoreactive cytotoxic T-lymphocytes. Based on recent observations we now hypothesize that a type I interferon-driven inflammation might be involved in the pathogenesis of this disease. Lesional skin biopsies were analysed by immunohistochemistry (CD3, CD4, CD8, CD68, CD123, Tia1, Granzyme B, Myxovirus resistance A, IP10/CXCL10 and CXCR3). Sequential double staining was performed to analyse co-expression of Tia1 and CXCR3. Significant expression of Myxovirus resistance A was found, indicating type I interferon production. This expression was closely associated with the expression of the interferon-inducible protein IP10 and the recruitment of CXCR3+ cytotoxic T-lymphocytes. Plasmacytoid dendritic cells appeared to be a major source of type I interferon in lichen sclerosus et atrophicus. Interestingly, several infiltrating lymphocytes contained IP10 in their granules. This is the first study providing evidence that a type I interferon-associated recruitment of CXCR3+ cytotoxic T-lymphocytes is involved in the pathogenesis of lichen sclerosus et atrophicus. Infiltrating lymphocytes, containing IP10 in their granules, could provide an important self-perpetuating mechanism. PMID- 17340018 TI - Clinical associations of the risk alleles of HLA-Cw6 and CCHCR1*WWCC in psoriasis. AB - The PSORS1 locus is the consistently replicated genetic risk factor for psoriasis. Clinical associations with the main marker allele of PSORS1, HLA-Cw6, have been addressed in a number of studies, but clinical associations have not been used as a way to distinguish the effects of the neighbouring candidate genes in PSORS1. Our results show that HLA-Cw6 and CCHCR1 risk allele associations with clinical features of psoriasis are predictably highly similar in a Finnish nationwide cohort of 379 psoriasis patients. The clinical profiling of a small group of patients (n=34) who were HLA-Cw6- but CCHCR1*WWCC positive suggested that no great differences existed between them and HCR-Cw6- patients. HCR+ genotype (as well as Cw6+ genotype) correlated for the first time positively with female sex and, in contrast with previous studies, negatively with disease severity. Presence of psoriatic arthritis was more pronounced in HCR- psoriasis (as well as in Cw6- psoriasis). Clinical profiling may be a useful approach to distinguishing genetic effects of candidate genes even within a locus in sufficiently large cohorts. PMID- 17340017 TI - Skin-homing CD8+ T lymphocytes show preferential growth in vitro and suppress CD4+ T-cell proliferation in patients with early stages of cutaneous T-cell lymphoma. AB - A total of 27 T-lymphocyte cell strains were established from skin biopsies of 24 patients with various stages of cutaneous T-cell lymphoma (CTCL) by addition of the T-cell growth factors interleukin (IL)-2 and IL-4. Cellular proliferation and phenotypic changes were measured over 3 months in culture, and T-cell clones were studied using T-cell receptor-? re-arrangement techniques. An average outgrowth of 134 million T-lymphocytes from a 4-mm skin biopsy was observed over 2 months. Initially, most T-cells expressed the CD4+ phenotype. In 17 cell strains from patients with early CTCL a statistically significant predominance of CD8+ T lymphocytes developed over 8-weeks' culture, indicating that CD8+ T-cells controlled the growth of CD4+ T cells, whereas CD4+ T-cells were predominant in cell strains from advanced CTCL (p <0.05). TCR-? re-arrangement studies revealed, on average, 12 T-cell clones per cell strain, which was reduced over time to 6 T cell clones per cell strain. Lymphocytes from peripheral blood could kill lymphocytes from an autologous cell strain, suggesting the presence of autoreactive cytotoxic T-cells. Our study suggests how skin-homing CD8+ T lymphocytes from patients with early stage CTCL can suppress the in vitro growth of skin-homing CD4+ T-lymphocytes, indicating immune surveillance. PMID- 17340019 TI - Study of psychological stress, sebum production and acne vulgaris in adolescents. AB - Sebum production is thought to play a major role in acne vulgaris in adolescents. Psychological stress may exacerbate acne; however, it is not known whether the perceived association between stress and acne exacerbation is due to increased sebum production. The aims of this study were to determine: (i) if psychological stress in adolescents is associated with increased sebum production; and (ii) if stress is associated with increased acne severity independent of, or in conjunction with, increased sebum production. Ninety-four secondary school students in Singapore (mean age 14.9 years) were enrolled in this prospective cohort study. During a high stress condition (prior to mid-year examinations) and a low stress condition (during the summer holidays), the following were evaluated: (i) self-reported stress level using the Perceived Stress Scale; (ii) sebum level at baseline and at 1 h; and (iii) acne severity. The prevalence of self-reported acne in this study population was high (95% in males and 92% in females). Most subjects had mild to moderate acne. Sebum measurements did not differ significantly between the high stress and low stress conditions. For the study population as a whole, we observed a statistically significant positive correlation (r=0.23, p=0.029) between stress levels and severity of acne papulopustulosa. In adolescents, psychological stress does not appear to affect the quantity of sebum production. The study suggests a significant association between stress and severity of acne papulopustulosa, especially in males. Increased acne severity associated with stress may result from factors other than sebum quantity. PMID- 17340020 TI - Pooling samples: the key to sensitive, specific and cost-effective genetic diagnosis of Chlamydia trachomatis in low-resource countries. AB - The aims of this study were to compare the performance characteristics and cost effectiveness of pooling endocervical samples for screening and diagnosis of Chlamydia trachomatis, and to investigate the prevalence of C. trachomatis infection in women in Leningrad Oblast, Russia. A total of 1500 endocervical samples were tested individually and when pooled in groups of 5 and 10 samples, respectively. A previously evaluated in-house diagnostic polymerase chain reaction (PCR) assay was utilized. The sensitivity and specificity of the PCR were not affected by either pooling strategy. The estimated prevalence of genital C. trachomatis infection was 6.6%, 6.1% and 6.0% based on individually tested samples, and pools of 5 and 10, respectively. For diagnosis of individual samples, the pooling strategies resulted in cost savings of 53.3% (5 samples per pool) and 44.0% (10 samples per pool). Pooling samples for PCR detection of C. trachomatis is an accurate and cost-saving approach for diagnosis and large-scale prevalence studies in St Petersburg, Russia. PMID- 17340021 TI - Dexamethasone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis. AB - Mortality in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is high. Apart from intensive supportive therapy, no generally accepted specific treatment regimen exists. The role of corticosteroids in SJS/TEN is controversial. It is possible that high-dose pulse therapy with corticosteroids might be an improvement on long-term lower dose therapy, by combining higher efficacy with a diminished risk both of infection and of delayed wound healing. The aim of this study was to evaluate the efficacy of dexamethasone pulse therapy with respect to mortality and healing time of patients with SJS/TEN. A small, uncontrolled series of consecutive inpatients with SJS/TEN was treated with dexamethasone pulse therapy. The efficacy of this treatment was assessed retrospectively using SCORTEN. Twelve patients were included over a period of 10 years. One patient died, while SCORTEN predicted a fatal outcome of 4 patients. Stabilization was reached after 2.3 days on average, total re-epithelialization after 13.9 days. The results of this study bear no statistical relevance due to the small number of patients. In conclusion, short-term dexamethasone pulse therapy, given at an early stage of the disease, may contribute to a reduced mortality rate in SJS/TEN without increasing healing time. A larger controlled trial is warranted to investigate further the use of dexamethasone pulse therapy in SJS/TEN. PMID- 17340022 TI - Poppyfield bleeding: a new dermatoscopic sign and its histopathological background. AB - Dermatoscopy increases the accuracy of diagnosis of melanoma. An atypical vascular pattern may be an indicator of cutaneous malignant melanoma (CMM). During dermatoscopy of certain CMMs numerous ruby droplets of blood appear when the dermatoscope is pressed firmly against the lesion. The aim of this paper was to examine the histopathological background for this observation. CMMs from 8 patients showing the poppyfield sign, i.e. squirts of ruby blood droplets, were paired with 8 CMMs of equal Breslow thickness not showing this sign. The 16 CMMs were placed in an unsystematic sequence and presented to two dermato-pathologists who assessed the lesions independently for confirmation of Breslow thickness, Clark level, ulceration and presence of dilated tumour vessels. There was no disagreement between the pathologists' assessments. Age of the patients and Breslow thickness of the cutaneous malignant melanoma were similar in the two groups. All 8 poppyfield CMMs had dilated tumour vessels compared with 25% (2/8) of the non-poppyfield CMMs (p< 0.007). Histological ulceration was observed in all poppyfield CMMs and none of the non-poppyfield CMMs (p< 0.001). The poppyfield bleeding sign is a dermatoscopic clue to dilated tumour vessels. It may be a dermatoscopic reflection of increased vascular density described in primary CMMs compared with adjacent skin and may also reflect the presence of primitive vessels in CMMs displaying increased fragility. PMID- 17340023 TI - Cutaneous vascular alterations in psoriatic patients treated with cyclosporine. AB - Videocapillaroscopy can be used to assess cutaneous microcirculation modifications in vivo, and therefore allows assessment of variations in the microvascular architecture in psoriatic subjects during treatment. The aim of this study was to observe and quantify the modifications of the superficial capillary bed in psoriatic plaques during treatment with cyclosporin A. Twelve patients with psoriasis vulgaris were treated with an initial dose of 4 mg/kg/day cyclosporin A over a period of 3 months with periodic clinical and capillaroscopic assessments. Clinical resolution of the lesions and a reduction in microcirculatory alterations was observed in 70% of patients, although none returned to a normal capillaroscopic pattern. PMID- 17340024 TI - CD13 and TCR clone: markers of early mycosis fungoides. AB - Making a differential diagnosis between early mycosis fungoides and parapsoriasis is often difficult at the clinical and histological level. The aim of this study was to explore markers that could help in this process. A total of 88 patients were included in 2 categories: large plaque parapsoriasis and digitiform parapsoriasis. A histological examination was performed for each patient, and expression of the antigen My7 (CD13), which is lacking in cutaneous T-lymphomas (but not in inflammatory lesions) and rearrangement of the T-cell receptor gene were analysed. A histological aspect of epidermotropic cutaneous T-cell lymphoma was observed in 23.5% of cases of large plaque parapsoriasis and 15% of cases of digitiform parapsoriasis. A disappearance of My7 antigen was noted in the 2 forms of parapsoriasis, more frequently when there was cutaneous T-cell lymphoma histology. A cutaneous clone was observed in 10.3% of cases of large plaque parapsoriasis, but not of digitiform parapsoriasis. For 3 patients, a cutaneous clone and a disappearance of My7 were associated with a non-specific histology. Considering these histological, immunological and molecular biological data, it appears that My7 antigen combined with T-cell clone may help the dermatologist to confirm the diagnosis of early mycosis fungoides. Moreover, further studies will determine whether CD13 is an early prognostic marker of evolution of a parapsoriasis to mycosis fungoides. Finally, these results demonstrate that digitiform parapsoriasis can be an early stage of MF. PMID- 17340025 TI - Spectrum of cutaneous metastases in 1287 cases of internal malignancies: a study from Turkey. AB - Cutaneous metastases may be either the initial manifestation of an internal malignancy or represent recurrent neoplastic disease. The aim of this study was to investigate the incidence and characteristics of cutaneous metastases in cases of internal malignancy. A total of 1287 patients with internal malignancy were included in the study. Dermatological examinations were performed on all of the patients. Skin biopsies were obtained from the suspected lesions. The type of malignancy, the time of diagnosis of the malignancy, the presence of cutaneous metastasis, and the localization sites of the cutaneous malignancy were noted. Metastases of any kind were seen in 27.4% of cases. Cutaneous metastases were seen in 1.2% of cases and were most frequently localized on the anterior chest as nodules. Cutaneous metastasis was the first sign of internal malignancy in one case. It is concluded that cutaneous metastases occur rarely and the presentation of internal malignancy with skin involvement is uncommon. PMID- 17340026 TI - Dermatitis herpetiformis presenting as ataxia in a child. AB - Dermatitis herpetiformis and coeliac disease are gluten-sensitive diseases that share immunopathological mechanisms. Neurological disorders are reported in both diseases, being more frequent in coeliac disease. Dermatitis herpetiformis is rare in paediatric populations and only sporadic cases with neurological dysfunction are reported. Uncertainty exists as to whether early treatment may stop or reverse neurological symptoms. We describe here the case of a child presenting with a rash and ataxia, diagnosed with dermatitis herpetiformis, in whom neurological symptoms and signs regressed after treatment. PMID- 17340027 TI - Treatment of psoriatic nails with tazarotene cream 0.1% vs. clobetasol propionate 0.05% cream: a double-blind study. PMID- 17340028 TI - Primary cutaneous diffuse large B-cell lymphoma, leg type, with the clinical picture of chronic venous ulceration. PMID- 17340029 TI - Non-Hodgkin's lymphoma associated with leiomyomatosis presenting with intense pruritus. PMID- 17340030 TI - Spiny keratoderma of the palms successfully treated with topical tacalcitol. PMID- 17340031 TI - Gianotti-Crosti syndrome after hepatitis A vaccination. PMID- 17340032 TI - Extranodal NK/T-cell lymphoma nasal type mimicking pyoderma gangrenosum. PMID- 17340033 TI - Contact vulvitis due to Pseudowintera Colorata in a topical herbal medicament. PMID- 17340034 TI - Adult-onset multiple eccrine angiomatous hamartoma in enlarging hairy plaques. PMID- 17340035 TI - Keratosis lichenoides chronica: treatment with bath-PUVA. PMID- 17340036 TI - Persistent herpes gestationis treated with high-dose intravenous immunoglobulin. PMID- 17340037 TI - A case of generalized argyria caused by the use of silver protein as a disinfection medicine. PMID- 17340038 TI - Assessing clinically meaningful end points for the management of actinic keratosis with diclofenac 3% gel. PMID- 17340039 TI - Genetic variation in the B-type natiuretic peptide pathway affects BNP levels. AB - PURPOSE: The importance of B-type natriuretic peptide (BNP) as a diagnostic and therapeutic modality in cardiovascular disease is well known. BNP levels correlate clinical and physiologic characteristics, as well as outcomes. We sought to investigate the influence of BNP pathway genetic variation on BNP levels after adjustment for clinical/physiologic factors. MATERIALS AND METHODS: DNA was extracted from 147 patients undergoing elective cardiac catheterization. Patients with elevated troponin were excluded. Detailed clinical data was collected including standard demographic, laboratory, echocardiographic and catheterization data. Genotype was determined at 19 loci in five genes relevant to the BNP pathway. Multivariable linear regression models of logBNP, adjusted for clinical variables, were used to assess the incremental influence of the genetic variants. RESULTS: Natriuretic peptide precursor B gene (NPPB) variants incrementally improved models of logBNP after inclusion of clinical/physiologic parameters. The NPPB -381 T > C genotype was significantly associated with logBNP in the model (p = 0.0005), with the model predicting 50% lower BNP levels in otherwise similar T/T vs. C/C subjects. The NPPB 777 G > A (3' flanking region) genotype was of borderline significance (p = 0.0078). None of the other genotypes examined were significant (all p > 0.2). CONCLUSIONS: Genetic variation in NPPB significantly impacts BNP levels after adjustment for clinical/physiologic factors. The full linear regression model predicted up to a 50% relative difference in BNP levels between NPPB -381 T > C genotype groups. This suggests that NPPB sequence variants affect BNP physiology, possibly via transcriptional regulation. Further studies are needed to define whether these variants impact the clinical interpretation of BNP levels. PMID- 17340041 TI - Enhancement of chemical rules for predicting compound reactivity towards protein thiol groups. AB - Non-specific chemical modification of protein thiol groups continues to be a significant source of false positive hits from high-throughput screening campaigns and can even plague certain protein targets and chemical series well into lead optimization. While experimental tools exist to assess the risk and promiscuity associated with the chemical reactivity of existing compounds, computational tools are desired that can reliably identify substructures that are associated with chemical reactivity to aid in triage of HTS hit lists, external compound purchases, and library design. Here we describe a Bayesian classification model derived from more than 8,800 compounds that have been experimentally assessed for their potential to covalently modify protein targets. The resulting model can be implemented in the large-scale assessment of compound libraries for purchase or design. In addition, the individual substructures identified as highly reactive in the model can be used as look-up tables to guide chemists during hit-to-lead and lead optimization campaigns. PMID- 17340042 TI - Antitumor agents 252. Application of validated QSAR models to database mining: discovery of novel tylophorine derivatives as potential anticancer agents. AB - A combined approach of validated QSAR modeling and virtual screening was successfully applied to the discovery of novel tylophrine derivatives as anticancer agents. QSAR models have been initially developed for 52 chemically diverse phenanthrine-based tylophrine derivatives (PBTs) with known experimental EC(50) using chemical topological descriptors (calculated with the MolConnZ program) and variable selection k nearest neighbor (kNN) method. Several validation protocols have been applied to achieve robust QSAR models. The original dataset was divided into multiple training and test sets, and the models were considered acceptable only if the leave-one-out cross-validated R (2) (q (2)) values were greater than 0.5 for the training sets and the correlation coefficient R (2) values were greater than 0.6 for the test sets. Furthermore, the q (2) values for the actual dataset were shown to be significantly higher than those obtained for the same dataset with randomized target properties (Y randomization test), indicating that models were statistically significant. Ten best models were then employed to mine a commercially available ChemDiv Database (ca. 500 K compounds) resulting in 34 consensus hits with moderate to high predicted activities. Ten structurally diverse hits were experimentally tested and eight were confirmed active with the highest experimental EC(50) of 1.8 microM implying an exceptionally high hit rate (80%). The same ten models were further applied to predict EC50 for four new PBTs, and the correlation coefficient (R (2)) between the experimental and predicted EC(50) for these compounds plus eight active consensus hits was shown to be as high as 0.57. Our studies suggest that the approach combining validated QSAR modeling and virtual screening could be successfully used as a general tool for the discovery of novel biologically active compounds. PMID- 17340043 TI - Yeast two-hybrid map of Arabidopsis TFIID. AB - General transcription factor IID (TFIID) is a multisubunit protein complex involved in promoter recognition and is fundamental to the nucleation of the RNA polymerase II transcriptional preinitiation complex. TFIID is comprised of the TATA binding protein (TBP) and 12-15 TBP-associated factors (TAFs). While general transcription factors have been extensively studied in metazoans and yeast, little is known about the details of their structure and function in the plant kingdom. This work represents the first attempt to compare the structure of a plant TFIID complex with that determined for other organisms. While no TAF3 homolog has been observed in plants, at least one homolog has been identified for each of the remaining 14 TFIID subunits, including both TAF14 and TAF15 which have previously been shown to be unique to either yeast or humans. The presence of both TAFs 14 and 15 in plants suggests ancient roles for these proteins that were lost in metazoans and fungi, respectively. Yeast two-hybrid interaction assays resulted in a total of 65 binary interactions between putative subunits of Arabidopsis TFIID, including 26 contacts unique to plants. The interaction matrix of Arabidopsis TAFs is largely consistent with the three-lobed topological map for yeast TFIID, which suggests that the structure and composition of TFIID have been highly conserved among eukaryotes. PMID- 17340044 TI - Acute polyarthritis revealing hepatitis E. AB - We report a case of acute hepatitis E occurring in a 51-year-old French woman, revealed by an abrupt onset of polyarthritis involving the ankles and knees followed by the wrists and fingers. Polyarthritis lasted up to 3 months without recurrence. Our case was characterised by a 9-month prolonged viraemia with persistence of specific IgM in the serum. The hepatitis E virus belonged to genotype 3 and may have been contracted in France or during travel to hyperendemic areas. Our case shows that acute polyarthritis could be another systemic manifestation of hepatitis E virus infection. PMID- 17340045 TI - Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients. AB - We report two rheumatoid arthritis patients developing sarcoidosis possibly induced by etanercept. Both women, aged 46 and 53, had erosive, rheumatoid-factor positive rheumatoid arthritis (RA) for 7 and 6 years, respectively. The eldest had received infliximab for over a year with good response, which was stopped because of a perfusion reaction. She developed a cough and dyspnea after 6 months of etanercept treatment. The other developed erythema nodosum and a plaque lesion on the right arm after 1 year of etanercept. Imaging showed, in both cases, mediastinal adenopathies. Biopsies were compatible with sarcoidosis. Etanercept withdrawal led to a complete remission. Recently, there have been reports of noninfectious granulomatous syndromes in patients receiving etanercept for a variety of diseases. In our cases, the temporal association with etanercept therapy and the complete remission after suspension of etanercept suggest a triggering role of this agent. Possible mechanisms of action and supporting evidence are discussed. PMID- 17340046 TI - A case of silent giant cell arteritis involving the entire aorta, carotid artery and brachial artery screened by integrated PET/CT. AB - We report a case of giant cell arteritis involving the aorta and several large arteries identified by integrated positron emission tomography (PET)/computed tomography (CT) obtained in a patient with a high erythrocyte sedimentation rate (ESR). A 63-year-old man with anemia and a high ESR noted on a regular medical examination was transferred to our department. The patient complained of only a low-grade general weakness for several months; there were no specific symptoms or signs. A PET was recommended. The image showed strong (18)F-fluorodeoxyglucose ((18)F-FDG) uptake at the ascending aorta, aortic arch, descending aorta, thoraco lumbar aorta, brachial artery, and the carotid artery wall, bilaterally. Suspicious for large-vessel vasculitis, a temporal artery biopsy was performed, which confirmed giant cell arteritis. After treatment with prednisolone, the high ESR and anemia resolved, and (18)F-FDG uptake decreased on follow-up integrated PET/CT. PMID- 17340047 TI - Obesity is independently associated with impaired quality of life in patients with rheumatoid arthritis. AB - Obesity is a modifiable major cause of morbidity and mortality in the general population, but little is known about the association of obesity and quality of life in patients with rheumatoid arthritis (RA). Thus, we set out a study to test the hypothesis that obesity is independently associated with lower quality of life in patients with RA. Three hundred and fifty nine patients with RA underwent an interview, physical exam, and all clinical charts were reviewed. Based on body mass index (BMI), patients were classified as normal (BMI < 25 kg/m(2)), overweight (BMI = 25-29.9 kg/m(2)), and obese (BMI > or = 30 kg/m(2)). Quality of life was quantified with the Medical Outcomes Study Short Form 36 (SF-36). Data obtained included demographic variables, extra-articular disease, comorbidities, presence of X-ray erosions, rheumatoid factor, and depression. The association between obesity and quality of life was examined with the use of multiple lineal regression models. One hundred and seventy-two patients (47.9%) had normal BMI, 126 (35.1%) were overweight, and 61 patients (17%) were obese. Obese patients had lower quality of life (30.8 +/- 18.1) than overweight patients (43.3 +/- 20.1) and patients with normal weight (43.8 +/- 22.2), P < 0.001. The association between obesity and impaired quality of life was confirmed with a linear regression model (Coef = -12.9, P < 0.001) and remained significant after adjustment for age, sex, disease activity, extra-articular disease, comorbidities, X-ray erosions, presence of rheumatoid factor, depression, education, and disease duration (Coef = -5.3, P = 0.039). In conclusion, obesity is independently associated with the impaired quality of life in patients with rheumatoid arthritis. PMID- 17340049 TI - The state of residency training in female pelvic medicine and reconstructive surgery. AB - To evaluate the state of resident training in female pelvic medicine and reconstructive surgery, the American Urogynecology Society (AUGS) education committee surveyed obstetrics and gynecology program directors on resident training and competence in performing common urogynecologic surgical and office procedure skills. One hundred thirty-two programs (50%) responded. Programs averaged 9 weeks of pelvic floor rotations during residency training. Program directors reported that 77% of residents could independently do some type of anti incontinence procedure, but only 58% could independently perform apical vaginal support procedures. In 85% of the programs, residents could perform without help only four out of ten urogynecological procedures identified as procedures that residents should be able to do independently by the Council for Resident Education in Obstetrics and Gynecology and AUGS' guidelines. PMID- 17340048 TI - Intercellular adhesion molecules in systemic lupus erythematosus patients with lupus nephritis. AB - Cardiovascular events are markedly increased in systemic lupus erythematosus (SLE), and the mechanism of atherogenesis remains poorly understood. Several methods have been employed to assess endothelial function, among these is the measurement of biomarkers of endothelial activation and dysfunction [intercellular adhesion molecule (ICAM-1)]. It has been reported that such biomarkers play a more important role than traditional risk factors in cardiovascular disease. The objectives of this study were to determine the level of ICAM-1 as markers of endothelial dysfunction in 40 Egyptian patients who have SLE with various degrees of activity and to investigate their relationship to disease activity. Sixty people (40 with SLE and 20 healthy as the control group) were the subject of this study; their clinical disease activity was scored according to the SLE disease activity index (SLEDAI), and serum sampling was obtained for ICAM-1 level assay. Renal biopsy was carried out and examined by light microscopy by a pathologist blinded to the clinical activity. The mean level of ICAM-1 was significantly higher in SLE patients with active disease (826.05 +/- 367.1 Pg/ml) compared to those with inactive disease (441.33 +/- 225.19 Pg/ml) and the healthy control volunteers (111.5 +/- 17.36 Pg/ml). There was a positive correlation between serum ICAM-1 and SLEDAI (r = 0.66). A high concentration of soluble ICAM-1 in SLE patients with nephritis is reported in this paper. Our finding of increased concentrations of ICAM-1 in SLE patients with nephritis underlines the importance of inflammation and endothelial involvement in this disease, but their predictive value in the disease monitoring need to be further studied. PMID- 17340050 TI - Sensitivity analysis of aggregated indices for integrated assessment with a case study of the Mid-Atlantic region. AB - Environmental indicators are often aggregated into a single index for various purposes in environmental studies. Aggregated indices derived from the same data set can differ, usually because the aggregated indices' sensitivities are not thoroughly analyzed. Furthermore, if a sensitivity analysis is carried out, it is not presented in a transparent fashion to policy decision-makers. This paper presents a method of generating various aggregated environmental indices and analyzing their sensitivities via the use of the fuzzy set concept. Results show that several insights into the environmental conditions of the study area (e.g., the distribution of good or bad values of indicators at a watershed and or across the region) can be revealed in the sensitivity analysis of aggregated indices. PMID- 17340052 TI - De Garengeot hernia: an analysis of our experience. AB - AIM: The presence of a vermiform appendix in a femoral hernia sac is termed De Garengeot hernia. It may present as a tender and/or erythematous groin swelling and is often misdiagnosed as an incarcerated or strangulated femoral hernia. The purpose of this study is to review the management of De Garengeot hernia at a single institution since 1991. MATERIALS AND METHODS: A retrospective analysis of seven consecutive patients operated upon at our institution from 1991 to 2006 with De Garengeot hernia was undertaken. Patients' demographics, treatment performed and postoperative outcome were analysed. RESULTS: There were three men and four women. The median age was 55 years. None of the patients were diagnosed preoperatively. The commonest presenting symptom was painful groin swelling. All patients therefore underwent emergency surgery with a presumptive diagnosis of either incarcerated or strangulated femoral hernia. Operative findings included four normal appendices, two inflamed appendices and one perforated appendix in the femoral hernial sac. Patients with normal appendix (n = 4) had mesh hernia repair without an appendicectomy. The rest of the patients (n = 3) with abnormal appendix underwent emergency open appendicectomy followed by sutured hernia repair. We had no deaths in this series and one minor wound infection. No recurrent hernia has been detected to date. CONCLUSION: Inflammation of the appendix determines the type of hernia repair and surgical approach. Incidental appendicectomy in the case of a normal appendix is not preferred. PMID- 17340053 TI - A rare complication following laparoscopic TEP repair: case report and discussion of the literature. AB - Transabdominal pre-peritoneal and totally extra-preperitoneal (TEP) are common laparoscopic techniques used to repair inguinal hernias. With better equipment and techniques for creation of pneumoperitoneum serious complications are now infrequent. However, complications from these techniques that are beyond the control of the surgeon do occur. This report details a rare complication related to infection. It is the first such documented complication of TEP hernia repair. There follows a short literature review of rare complications of laparoscopic hernia repair. Surgeons should familiarize themselves with these potential pitfalls for a number of reasons including, counseling when obtaining consent and heightened awareness for infrequent complications during postoperative follow-up. PMID- 17340054 TI - Potential foramen to allow communication between the pleural cavity and retroperitoneal space during laparoscopic surgery: a cadaver study of Bochdalek's triangle. AB - The indications for laparoscopic retroperitoneal surgery have recently been greatly extended and the technique has become popular, but concomitant pleural injury or pneumothorax has been reported from numerous hospitals in Japan. Which anatomical information is useful to avoid surgical injury of the suggested weak portion of the diaphragm? We identified a diaphragm-free triangular area or Bochdalek's triangle in 90.1% of elderly Japanese cadavers (100/111 cadavers), comprising about 622.8 mm(2) in area (height 47.9 mm, base 25.0 mm). In most cases (80.1%; 129/161), the entire triangle was restricted to the superior side of the 12th rib in addition to the medial side of the distal end of the rib. A "potential foramen" (PF) was defined as the diaphragm-free triangle >100 mm(2) in area on the parietal pleura. Most triangles (77.6%, 125/161) met this criterion. The PF was often covered by the kidney (93.3%), and had a mean area of 318.9 mm(2). The PF was located 42.3 mm from the distal end of the 12th rib, while the inferior pleural margin was 27.8 mm superior to the rib end. When the triangle was large, the PF was also large, with the PF often occupying >50% of the triangle area (62/125; 49.6%). To avoid the distal end of the 12th rib, in laparoscopic retroperitoneal surgery, we recommend making a transverse skin incision at the midpoint between the end of the 12th rib and the iliac crest. PMID- 17340055 TI - Prevalence and clinical characteristics of oral tori in 1,520 Chulalongkorn University Dental School patients. AB - The objectives of this study were to determine the prevalence, size, shape and location of the oral tori in 1,520 Thai dental patients and to investigate the relationship between the findings with age and gender. The prevalence rates were 60.5% for torus palatinus (TP) and 32.2% for torus mandibularis (TM). The concurrence of TP and TM was noted in 23.2% subjects. The peak incidence of TP and TM was in the third decade of life. TP affected more women than men (70.5 vs. 48.8%, P < 0.001). Most TP were found in spindle shape (56%), small size (52.1%) and located at premolar region (47.4%). The occurrence of TM was higher in men than in women (36.3 vs. 28.6%, P = 0.002). TM was found most common in small size (65.6%), as bilateral multiple nodes (59.3%) and usually located at the premolars (89.2%). The age and gender-related differences with the size of tori were noted. Subjects who had larger TP or TM were older than those who had smaller TP or TM (P < 0.001 and P = 0.001, respectively). Women were more likely to have larger TP whereas men tended to have larger TM. This study showed high prevalence rates of TP and TM in dental patients and the occurrences were related to gender. PMID- 17340056 TI - Import and localisation of nucleoside diphosphate kinase 2 in chloroplasts. AB - Nucleoside diphosphate kinases (NDPKs) are key enzymes that are involved in the homeostasis of nucleoside triphosphates (NTPs). Different isoforms exist, which are found in diverse cell compartments, for example the cytosol, mitochondria, and plant chloroplasts. NDPK2 of Pisum sativum has been shown to be localised in chloroplasts. Two forms of different size have been reported in plastids and it has been speculated that they function in distinct suborganellar compartments. We investigated the import behaviour and localisation of these two isoforms. Our results indicate that they do not differ in their route of entry into the organelle and both forms end up in the chloroplast stroma. PMID- 17340057 TI - High dose aspirin and left ventricular remodeling after myocardial infarction: aspirin and myocardial infarction. AB - BACKGROUND: Proinflammatory proteins like inflammatory cytokines are implicated in myocardial depression and left ventricular remodeling after myocardial infarction. High-dose aspirin inhibits cytokine activation. Therefore, we tested the influence of high-dose aspirin treatment on left ventricular remodeling in mice after myocardial infarction. METHODS AND RESULTS: Mice were treated for 4 weeks with placebo or aspirin (120 mg/kg per day) by Alzet mini-osmotic pumps after ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography was performed at days 1, 7, and 28. Over the 4 weeks, mortality was not different between the groups (placebo 30.8%, aspirin 30.8%). On echocardiography, animals after myocardial infarction exhibited left ventricular dilatation (week 4, end-systolic area, placebo sham 8.9 +/- 1.7 vs. placebo MI 15.9 +/- 2.5 mm(2)), which was not changed by aspirin treatment (week 4, end-systolic area, aspirin MI 14.5 +/- 1.3 mm(2), p= ns vs. placebo MI). The expression of the proinflammatory cytokines TNF and IL-1beta were markedly upregulated in mice with myocardial infarction on placebo. Cytokine expression was significantly reduced by aspirin treatment while collagen deposition was not influenced. CONCLUSION: Continuous aspirin treatment (120 mg/kg/d) reduces the expression of proinflammatory cytokines after myocardial infarction, but does not affect post-infarct cardiac remodeling and cardiac function. PMID- 17340058 TI - [10 years Innsbruck cardiology]. PMID- 17340059 TI - [Biomarkers in cardiology--state of the art 2007]. AB - Biomarkers have gained increasing significance in clinical cardiology during the last two decades. Laboratory parameters play an important role as risk markers for coronary events in primary and secondary prevention, in the diagnosis of acute myocardial necrosis and heart failure as well as in the management of patients with heart valve diseases. The development of novel biochemical markers has also led to new insights in the pathophysiology of coronary artery disease, acute coronary syndromes and heart failure. This review summarizes the state of the art of cardiac biomarkers suitable for routine use. PMID- 17340060 TI - [Asymmetric dimethyl arginine (ADMA): a novel cardiovascular risk factor?]. AB - Functional changes of the vessel wall--specifically dysfunction of endothelial cells--may precede the formation of frank plaques at the initiation of atherosclerosis. Clinically endothelial function and dysfunction can be measured by angiography or ultrasound techniques. Another possibility is the measurement of circulating markers of endothelial dysfunction in human plasma, such as the endogenous NOS inhibitor ADMA (asymmetric dimethylarginine). In our recent studies we were able to show that ADMA accumulates in the presence of metabolic changes such as hyperhomocysteinemia, insulin resistance and type-2 diabetes, and that these elevations of plasma ADMA correlate well with the amount of endothelial dysfunction and with NO bioavailability. Furthermore ADMA was shown to be dynamically regulated and to play an important patho-physiologic role in myocardial ischemia and reperfusion. Thus, measurements of plasma ADMA in patients could help to screen for manifestations of atherosclerosis. Moreover attempts to reduce plasma and tissue ADMA could potentially play an important role in the treatment of endothelial dysfunction, atherosclerosis, but also of ischemia reperfusion injury. PMID- 17340061 TI - [Clinical development of cardiac CT diagnostics: clinical and scientific applications from the cardiologist's point of view]. AB - The development of cardiac CT imaging has been extraordinary in the last few years. Due to excellent cooperation with our radiology departments we have been able to gain a very close insight into the newest clinical and technical improvements made in this field. The following article aims to highlight the relevant, practically orientated indications and applications of cardiac CT. Furthermore you will find a summary of clinically driven multicenter and interdisciplinary scientific work using this fascinating imaging modality. PMID- 17340062 TI - [Magnetic resonance tomography and spectroscopy investigations of the human heart]. AB - The use of cardiac magnetic resonance (CMR) has emerged in the last decades. Technical innovations provide fast and high-quality imaging sequences and CMR is often proposed as a gold-standard for the in vivo evaluation of cardiac function, morphologic details and infarct size. Also the 31-phosphorous magnetic resonance spectroscopy (MRS) is a unique tool to investigate the human myocardial high energy phosphate (HEP) metabolism in vivo. PCr/b-ATP ratio examined by MRS is mainly used as an index for cardiac energy metabolism. We have described decreased PCr/b-ATP ratios in patients with diabetes mellitus, hypercholesterolemia and hemochromatosis. The use of CMR to study the effects of ischemia time on the evolution of myocardial infarct characteristics after an acute myocardial infarction (AMI) treated with a primary angioplasty (p-PTCA) is a promising new application of this technique. Results of this study will further help to clarify the impact of ischemia time on myocardial regional functional recovery after p-PTCA. PMID- 17340063 TI - [Intracardiac and intraluminal echocardiography as a guiding tool in device closure of atrial septal defect and for detection of particular lesions in aortic dissection]. AB - This study sought to compare intracardiac echocardiography (ICE) with conventional quantitative cineangiography (QCA) for balloon-sizing of atrial septal defects (ASD) in order to develop a safe alternative to that radiation exposing part of device-closure procedures. In 45 patients with ASD, the stretched balloon diameter was measured by both ICE and QCA. The latter was considered the gold standard and done in two perpendicular planes whereas ICE balloon sizing was performed in a single standard cut plane, only. Echocardiographic measurements underestimated the diameter, but to a low extent: 0.7+/-0.8 mm (r=0.98; p<0.001). As a tool for sizing, ICE is an accurate alternative to QCA in order to reduce radiation exposure. If ICE is used, the occluder should be oversized by about 1 mm to account for the slight underestimation inherent in ICE sizing. Transesophageal echocardiography (TEE) and conventional intravascular ultrasound (IVUS) have limited capabilities in type B aortic dissection. To evaluate its diagnostic value, intraluminal phased array imaging was compared with IVUS and TEE. In 23 patients with type B aortic dissection, IPAI was tested with respect to its ability to depict true and false lumen (TL, FL) and to identify all entries. Intraluminal echocardiography detected more entries than IVUS (3.0+/-1.2 vs. 0.8+/-0.5; p<0.001) and thoracic IPAI depicted more entries than TEE (1.8+/-1.0 vs. 1.2+/-0.5; p<0.001). In the detailed diagnostic evaluation of type B aortic dissection, intraluminal echocardiography is superior to IVUS and TEE in detecting communications between the TL and FL. PMID- 17340064 TI - Effect of atorvastatin on peripheral endothelial function and systemic inflammatory markers in patients with stable coronary artery disease. AB - BACKGROUND: Endothelial dysfunction, detectable by an impaired flow-mediated vasodilation (FMD) of the brachial artery, has been shown to be associated with increased levels of circulating proinflammatory markers. Therapeutic interventions such as lipid-lowering with statins increase FMD and decrease inflammatory markers, like soluble (s) E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) or high-sensitivity Creactive protein (hsCRP). The effect of atorvastatin therapy on both FMD and inflammatory markers in patients with stable coronary artery disease (CAD) has not been investigated. METHODS: Thirty hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. FMD was assessed using highresolution ultrasound (13 MHz, Acuson Sequoia, C256). High-sensitivity CRP was measured with Latex agglutination assay, sE selectin and sICAM-1 were determined with ELISA. RESULTS: Baseline characteristics were not different between groups. FMD improved in patients on atorvastatin (6.7+/-3.8% to 8.5+/-4.4%; p<0.01), but remained unchanged in placebo-treated patients (8.2+/-3.3% to 8.9+/-5.1%; p=NS). Atorvastatin treatment was associated with decreases of sICAM-1 (from 274.2+/-92.2 to 197.9+/-70.0 ng/ml; p<0.01) and hsCRP (from 0.57+/-0.45 to 0.18+/-0.15 mg/dl; p<0.01), whereas placebo treatment had no effect on these markers. sE-selectin levels were not influenced by either treatment. No correlations were found between changes in FMD, lipids and inflammatory markers. CONCLUSIONS: Treatment with atorvastatin leads to an improvement in endothelial function and a reduction in inflammatory markers in patients with stable CAD. The lack of correlation between changes in FMD and inflammatory markers may support the concept of pleiotropic effects of statins in humans. PMID- 17340065 TI - [In vivo mouse model for myocardial ischemia-reperfusion]. AB - The past few years have witnessed a remarkable advance in our understanding of the pathophysiology of coronary heart disease. Myocardial ischemia usually occurs on the basis of coronary atherosclerosis. Although the functional consequences of depriving the myocardium of its blood supply have been appreciated for many years, coronary heart disease is still the leading cause of morbidity and mortality in the western world. This has focused the attention of physicians on restoring blood flow to the ischemic region in order to prevent tissue necrosis and regain organ function. Reperfusion of ischemic tissues is often associated with microvascular dysfunction that is manifested as impaired endothelial dependent dilatation in arterioles and leukocyte plugging in capillaries. The availability of a broad variety of knockout mice provides important clues about the progression of the ischemia/reperfusion (I/R) injury. Therefore mouse models for I/R are of great importance for the development of new therapeutic strategies for humans. PMID- 17340066 TI - [Changes in carbohydrate metabolism and insulin resistance in patients with Prader-Willi Syndrome (PWS) under growth hormone therapy]. AB - BACKGROUND: Life expectance and life quality have markedly changed in PWS patients within the last 10-15 years. A strict diet, improved physical activity and an additive growth hormone treatment have led to these changes. Growth hormone therapy decreases body fat and improves final height. But growth hormone also antagonizes insulin and therefore increases the diabetic potential. The purpose of our study was to investigate incidence and multiple dependencies of development of impaired carbohydrate metabolism in patients with PWS under growth hormone therapy and to determine suitable parameters for the work-up. PATIENTS AND METHODS: 34 patients with genetically approved PWS have been treated with growth hormone for at least 0.5 years. The mean duration of growth hormone treatment was 2.15 years (0.5-4.51). At the start of growth hormone treatment patients were 1.33 to 16.47 years old. The clinical picture and the nutritional situation of children with PWS change age-dependent and can be divided up into three phases. The patients were duty subdivided into three age-groups at the beginning of growth hormone treatment. Group 1: 15 PWS patients, mean age 2.62 years (1.33-3.78). Group 2: 10 PWS patients, mean age 5.54 years (4.08-7.61). Group 3: 9 PWS patients, mean age 11.35 years (8.89-16.47). Data were collected within 0.3-0.38 years before start of treatment and every 6 months throughout the treatment period. Anthropometrical data, fat mass by bioelectric impedance analysis (BIA), fasting insulin, HbA1c, C-peptide, blood fats and the blood sugar profile in oral glucose tolerance tests (OGT/1.75 g glucose/kg body mass) were obtained. Growth hormone therapy was started with an average dose of 0.031 mg/kg body mass in all groups. Insulin resistance was based on Homeostasis Model Assessment-Test (HOMA). RESULT: No IR or pathological OGT were detected when growth hormone therapy started before the 4th year of life. When therapy started between the 4th and 8th year, PWS patients with normal weight did not develop an IR under GH therapy. 6% developed a glucose tolerance (IGT) disorder and 4% developed an increased fasting glucose (IFG). 5 of 9 PWS patients older than 8 years at therapystart showed a transient disorder of glucose metabolism: 11% of the results obtained in these patients presented an IR with no pathological OGT, 13% showed an IR with IGT, 7% showed an IR with IFG, and 2% showed an IR with transient diabetes. For 4% the IFG persisted with no IR, for 4% the IGT persisted with no IR. These patients differed from younger ones by an increased average BMI, an increase fat body ratio and an increase fasting insulin as well as an already reached puberty. No difference was found in C-peptide, HbA1c or GH dose/kg/body mass. CONCLUSION: Transient glucose metabolism disorders with no development of manifest insulin resistance are shown by PWS patients with normal weight starting from 4th year under GH therapy. Changes in the glucose metabolism with and with no development of IR appear after start of puberty and weight increase. Changes persisted partially for 18 months. GH therapy was not interrupted for any patient, whereby physical training and dietetic measurements were increased for all patients. HOMA-index and OGT shall be used in parallel to monitor glucose metabolism as both show independently distinctive features. HbA1c and C-peptide are not suitable parameters for monitoring carbohydrate metabolism in PWS patients under GH treatment. PMID- 17340068 TI - Digitalization and networking of analog simulators and portal images. AB - BACKGROUND: Many departments have analog simulators and irradiation facilities (especially cobalt units) without electronic portal imaging. Import of the images into the R&V (Record & Verify) system is required. MATERIAL AND METHODS: Simulator images are grabbed while portal films scanned by using a laser scanner and both converted into DICOM RT (Digital Imaging and Communications in Medicine Radiotherapy) images. RESULTS: Image intensifier output of a simulator and portal films are converted to DICOM RT images and used in clinical practice. The simulator software was developed in cooperation at the authors' hospital. CONCLUSION: The digitalization of analog simulators is a valuable updating in clinical use replacing screen-film technique. Film scanning and digitalization permit the electronic archiving of films. Conversion into DICOM RT images is a precondition of importing to the R&V system. PMID- 17340069 TI - Efficacy of Wobe-Mugos E for reduction of oral mucositis after radiotherapy : results of a prospective, randomized, placebo-controlled, triple-blind phase III multicenter study. AB - PURPOSE: To investigate the efficacy and safety of Wobe-Mugos E (proteolytic enzymes) for amelioration of early side effects of radiotherapy for head-and-neck tumors, particularly oral mucositis. PATIENTS AND METHODS: The study was a prospective, randomized, multicenter, placebo-controlled, triple-blind phase III study with parallel groups. 69 patients with carcinomas of the oropharynx or the oral cavity were enrolled between 1996 and 2000 in five centers; 54 of these were recruited in Dresden. Of the 69 patients, 61 (Dresden: 46) were available for analysis. The proteolytic enzymes tested (Wobe-Mugos E) comprised papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg. RESULTS: Wobe-Mugos E was well tolerated. For the maximum mucositis scores, no statistically significant differences were found between the placebo and the verum group. The average mucositis score over weeks 1-6 revealed a significant difference in favor of the placebo arm, based on an earlier onset of mucositis in the Wobe-Mugos E group. CONCLUSION: The present study failed to demonstrate any effect of treatment with Wobe-Mugos E on radiotherapy side effects in patients treated for head-and-neck tumors. In particular, there was no beneficial effect on radiation-induced early oral mucositis. PMID- 17340070 TI - Phase I trial of radiochemotherapy with bendamustine in patients with recurrent squamous cell carcinoma of the head and neck. AB - BACKGROUND AND PURPOSE: After initial radiochemotherapy of head-and-neck cancers, therapeutic options are often limited for patients with progressive disease. Reirradiation, with or without chemotherapy, appears to be the most potential treatment option. The aim of this study was to determine the maximum tolerated dose of bendamustine in combination with reirradiation for these patients. PATIENTS AND METHODS: 13 patients with recurrent squamous cell carcinoma of the head-and-neck region after initial radiochemotherapy were treated. Reirradiation of the recurrent region under protection of the spinal cord consisted of 1.8 Gy given five times per week, up to 30.6 Gy. Simultaneous bendamustine was administered on days 1 and 2 at increasing dose levels (80, 100, and 120 mg/m(2) bendamustine). The regimen was administered every 4 weeks. A minimum of three patients were enrolled at each dose level. RESULTS: The therapy was well tolerated. Patients received one to six cycles of bendamustine (median: three). Hematologic toxicities observed were leukocytopenia, thrombocytopenia, or anemia. At dose level II (100 mg/m(2) bendamustine), grade 3/4 hematologic toxicity was seen in one patient so that this level was filled up to six patients. There was no grade 3/4 toxicity seen in the other twelve patients. The most frequent nonhematologic toxicities (grade 1 or 2) were infections (in most cases C reactive protein elevations without other clinical signs of infection) and nausea. CONCLUSION: The reapplication of radiochemotherapy with bendamustine is well tolerated. The recommended dose for phase II studies was established at dose level III (bendamustine 120 mg/m(2)). PMID- 17340071 TI - Curative brachytherapy for recurrent/residual tongue cancer. AB - PURPOSE: The efficacy of curative low-dose-rate (LDR) brachytherapy for recurrent and/or residual cancer following radical operation or irradiation and posttreatment quality of life (QoL) were assessed. PATIENTS AND METHODS: Between January 1979 and April 2004, 88 patients who had received curative LDR brachytherapy (28 with postoperative close or positive margins, six with postoperative recurrence, six with recurrence after external-beam irradiation, and 48 with recurrent/residual cancer after curative brachytherapy) were analyzed retrospectively. Late complications were assessed based on the RTOG/EORTC late radiation morbidity score scheme. RESULTS: The 5-year relapse-free and cause specific survival rates were 92% and 96%, respectively, in the close/positive margin group and 52% and 56%, respectively, in the postbrachytherapy recurrence or residual cancer group. The incidence of late side effects was 8% (2/26) in the close or positive margin group and 22% (4/18) in the postbrachytherapy group. The only grade 4 late complication (bone exposure) was observed in one patient in the postbrachytherapy group. CONCLUSION: LDR brachytherapy as reirradiation for recurrent/residual tongue cancer was effective, and there was no increase in complications. PMID- 17340072 TI - [Frequency and distribution pattern of distant metastases in patients with ENT tumors and their consequences for pretherapeutic staging]. AB - PURPOSE: To address the following questions: which parameters influenced the frequency of distant metastases in patients with locally advanced ear-nose-throat (ENT) tumors, which was the distribution pattern of metastases, and what were the diagnostic consequences for pretherapeutic staging? PATIENTS AND METHODS: 600 patients (526 men, 76 women, median age 56 years) with ENT tumors (squamous cell carcinoma histology) were studied retrospectively. The distribution of primary tumor site and stage (AJCC) was as follows: oropharynx: n = 161 (26.8%), hypopharynx: n = 187 (31.2%), oral cavity: n = 89 (14.8%), larynx: n = 118 (19.7%), cancer of unknown origin: n = 13 (2.2%), others: n = 32(5.3%), I: n = 24 (4%), II: n = 49 (8.2%), III: n = 89 (14.8%), IV: n = 438 (73%). 270 patients (45%) received radiochemotherapy, 330 (55%) postoperative radiotherapy. The following parameters were analyzed in association with distant metastases: tumor localization, T- and N-category, primary treatment, local tumor control, and second neoplasms. RESULTS: 114/600 patients (19%) developed distant metastases, 29/600 (4.9%) at presentation, 50% within 9.3 months after diagnosis of the primary tumor. Distant metastases were most frequent in stage IV (24.2%), carcinoma of the hypopharynx (25.7%), local recurrence (24.3%), and second neoplasm (31.7%) with the following distribution pattern: pulmonary 61/114 (53.5%), pleural 15/114 (13.1%), osseous 45/114 (39.5%), hepatic 14/114 (12.3%), cerebral 8/114 (7%), cutaneous 14/114 (12.3%). 34/114 patients (29.8%) presented monotopic, 80/114 (70.2%) polytopic metastases. 82/600 (13.6%) patients additionally had second neoplasms, 20 corresponding with synchronous or metachronous bronchial tumors. CONCLUSION: With locally advanced ENT tumor stage IVa/b, carcinoma of the hypopharynx, local recurrence or second neoplasms, at least a pretherapeutic CT of the thorax should be performed because every seventh patient (88/600) developed metastases or second primary tumors within the thoracic space during the course of disease. Regarding the side effects and costs of curative therapy, the definition of generally accepted guidelines for the systemic staging of locally advanced ENT tumors should be undertaken. PMID- 17340073 TI - Expression of HIF-1 alpha in irradiated tissue is altered by topical negative pressure therapy. AB - BACKGROUND AND PURPOSE: Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients. MATERIAL AND METHODS: With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1 alpha (hypoxia-inducible factor-1 alpha), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples. RESULTS: In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1 alpha-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples. CONCLUSION: This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1 alpha expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1 alpha concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation induced tissue injury, further investigations of HIF-1 alpha regulation under TNP are warranted. PMID- 17340074 TI - [Experimental validation of a Monte Carlo-based treatment-planning system for electron beams]. AB - BACKGROUND: Commercial, Monte Carlo-based 3-D treatment-planning systems will become more important for electron beams, e. g., for combined electron-photon fields or for intensity-modulated electron beams. MATERIAL AND METHODS: Using the commercial Monte Carlo algorithm (Oncentra MasterPlan 1.42), simulations were compared with measured data for electron energies from 4 MeV to 18 MeV of an Elekta linear accelerator. For the standard applicator size 14 x 14 cm(2) different square and rectangular apertures down to 2 x 2 cm(2) and arranged symmetrically as well as asymmetrically were fabricated. After optimizing the simulation parameters, depth dose curves, profiles and output factors were compared. RESULTS: The results for standard electron applicators are satisfying in most cases. However, a major problem of this actual release is the resolution of the calculation matrix fixed by phantom size. From there, larger deviations up to 11% occur with decreasing aperture size for low and high electron energies, especially in the output factors. At medium electron energies and not too small apertures the simulations can be used clinically. CONCLUSION: The Monte Carlo algorithm of the Oncentra MasterPlan treatment-planning system 1.42 can be used clinically in a wide range. However, a critical checkup of the results is necessary because nonacceptable deviations at low and high electron energies can occur in small electron fields. PMID- 17340075 TI - Such a tease: intentional sexual provocation within heterosexual interactions. AB - Sexual teasing is a form of provocation characterized by the promise of sexual contact followed by withdrawal. The intention is to frustrate or cause tension in the target and incorporates some use of power of one person over another. To date, this form of interaction between individuals has received little research attention. A total of 742 undergraduate university students (143 men, 599 women) provided reports regarding whether they had ever engaged in sexual teasing and, for those who had, the motives behind this behavior, the type of relationship and sexual history with the target, and the reactions and outcomes associated with these interactions. Sexual teasing was relatively common among both women and men, although women were significantly more likely to report having engaged in sexual teasing at least once in the past. The outcomes associated with their interactions were perceived to be more positive for participants (elicitors) than for their targets, although relatively few participants reported more adverse outcomes from the use of sexual teasing. Discussion focused on the need to better characterize forms of communication regarding sexual intentions and consent. The findings may have implications for efforts to improve models of communication and negotiation in sexual interactions. PMID- 17340076 TI - Resolution of overlapping signals in spectrometry using a wavelet packet transform and an Elman recurrent neural network. AB - A novel method named a wavelet packet transform based Elman recurrent neural network (WPTERNN) was proposed for the simultaneous UV-visible spectrometric determination of Cu(II), Cd(II) and Zn(II). This method combined wavelet packet denoising with an Elman recurrent neural network. A wavelet packet transform was applied to perform data compression, to extract relevant information, and to eliminate noise and collinearity. An Elman recurrent network was applied for nonlinear multivariate calibration. In this case, using trials, the kind of wavelet function, the decomposition level, and the number of hidden nodes for the WPTERNN method were selected as Daubechies 14, 3, and 8, respectively. A program (PWPTERNN) was designed that could perform the simultaneous determination of Cu(II), Cd(II) and Zn(II). The relative standard errors of prediction (RSEP) obtained for all components using WPTERNN, a Elman recurrent neural network (ERNN), partial least squares (PLS), principal component regression (PCR), Fourier transform based PCR (FTPCR), and multivariate linear regression (MLR) were compared. Experimental results demonstrated that the WPTERRN method was successful even where there was severe overlap of spectra. The results obtained from an additional test case also demonstrated that the WPTERNN method performed very well. PMID- 17340077 TI - Bioanalytical procedures for detection of chemical agents in hair in the case of drug-facilitated crimes. AB - The use of a drug to modify a person's behavior for criminal gain is not a recent phenomenon. However, the recent increase in reports of drug-facilitated crimes (sexual assault, robbery) has caused alarm in the general public. The drugs involved can be pharmaceuticals, such as benzodiazepines (flunitrazepam, lorazepam, etc.), hypnotics (zopiclone, zolpidem), sedatives (neuroleptics, some anti-H1) or anaesthetics (gamma-hydroxybutyrate, ketamine), drugs of abuse, such as cannabis, ecstasy or LSD, or more often ethanol. To perform successful toxicological examinations, the analyst must follow some important rules: (1) obtain as soon as possible the corresponding biological specimens (blood and urine); (2) collect hair about 1 month after the alleged event; (3) use sophisticated analytical techniques (gas or liquid chromatography coupled to tandem mass spectrometry, MS/MS, headspace gas chromatography); and (4) take care in the interpretation of the findings. Drugs used to facilitate sexual assaults can be difficult to detect (active products at low doses, chemical instability), possess amnesic properties and can be rapidly cleared from the body (short half life). In these situations, blood or even urine can be of low interest. This is the reason why some laboratories have developed an original approach based on hair testing. Hair was suggested as a valuable specimen in situations where, as a result of a delay in reporting the crime, natural processes have eliminated the drug from typical biological specimens. While there are a lot of papers that have focused on the identification of drugs in hair following chronic drug use, those dealing with a single dose are very scarce. The experience of the author and a review of the existing literature will be presented for cases involving benzodiazepines, hypnotics, gamma-hydroxybutyrate and various sedatives or chemical weapons. The expected concentrations in hair are in the low picogram/milligram range for most compounds. Hair analysis may be a useful adjunct to conventional drug testing in sexual assault. It should not be considered as an alternative to blood and urine analyses, but as a complement. This approach may find useful applications, but the definition of legally defensible cutoff values would require much more data. MS/MS technologies appear as a prerequisite in drug-facilitated cases. PMID- 17340078 TI - Simultaneous determination of trace levels of ethylmercury and methylmercury in biological samples and vaccines using sodium tetra(n-propyl)borate as derivatizing agent. AB - Because of increasing awareness of the potential neurotoxicity of even low levels of organomercury compounds, analytical techniques are required for determination of low concentrations of ethylmercury (EtHg) and methylmercury (MeHg) in biological samples. An accurate and sensitive method has been developed for simultaneous determination of methylmercury and ethylmercury in vaccines and biological samples. MeHg and EtHg were isolated by acid leaching (H2SO4-KBr CuSO4), extraction of MeHg and EtHg bromides into an organic solvent (CH2Cl2), then back-extraction into Milli-Q water. MeHg and EtHg bromides were derivatized with sodium tetrapropylborate (NaBPr4), collected at room temperature on Tenax, separated by isothermal gas chromatography (GC), pyrolysed, and detected by cold vapour atomic fluorescence spectrometry (CV AFS). The repeatability of results from the method was approximately 5-10% for EtHg and 5-15% for MeHg. Detection limits achieved were 0.01 ng g-1 for EtHg and MeHg in blood, saliva, and vaccines and 5 ng g-1 for EtHg and MeHg in hair. The method presented has been shown to be suitable for determination of background levels of these contaminants in biological samples and can be used in studies related to the health effects of mercury and its species in man. This work illustrates the possibility of using hair and blood as potential biomarkers of exposure to thiomersal. PMID- 17340079 TI - Identification of proteinaceous binders used in artworks by MALDI-TOF mass spectrometry. AB - Proper identification of proteinaceous binders in artworks is essential for specification of the painting technique and thus also for selection of the restoration method; moreover, it might be helpful for the authentication of the artwork. This paper is concerned with the optimisation of analysis of the proteinaceous binders contained in the colour layers of artworks. Within this study, we worked out a method for the preparation and analysis of solid samples from artworks using tryptic cleavage and subsequent analysis of the acquired peptide mixture by matrix-assisted laser desorption/ionisation time of flight mass spectrometry. To make this approach rational and efficient, we created a database of commonly used binders (egg yolk, egg white, casein, milk, curd, whey, gelatine, and various types of animal glues); certain peaks in the mass spectra of these binders, formed by rich protein mixtures, were matched to amino acid sequences of the individual proteins that were found in the Internet database ExPASy; their cleavage was simulated by the program Mass-2.0-alpha4. The method developed was tested on model samples of ground layers prepared by an independent laboratory and then successfully applied to a real sample originating from a painting by Edvard Munch. PMID- 17340080 TI - European analytical column No. 35 (January 2007). PMID- 17340082 TI - Solution to the neurochemical challenge. PMID- 17340083 TI - Quality assurance challenge 5. PMID- 17340084 TI - Simultaneous analysis of classical neuroleptics, atypical antipsychotics and their metabolites in human plasma. AB - A high-performance liquid chromatographic method has been developed for the simultaneous determination of classical neuroleptics (chlorpromazine, haloperidol, loxapine and clotiapine), atypical antipsychotics (clozapine, quetiapine and risperidone) and their active metabolites (N-desmethylclozapine, clozapine N-oxide and 9-hydroxyrisperidone) in human plasma. Separation was obtained by using a C8 reversed-phase column and a mobile phase composed of 70% aqueous phosphate buffer containing triethylamine at pH 3.0 and 30% acetonitrile. The UV detector was set at 238 nm and amitriptyline was used as the internal standard. A careful pre-treatment procedure of plasma samples was developed, using solid-phase extraction with cyanopropyl cartridges, which gives high extraction yields (>or=93%). The limits of quantitation (LOQ) were always lower than 2.6 ng mL-1 and the limits of detection (LOD) were always lower than 0.9 ng mL-1 for all analytes. The method was applied with success to plasma samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotics. Precision data and accuracy results were satisfactory and no interference from other central nervous system (CNS) drugs was found. Hence the method is suitable for the therapeutic drug monitoring (TDM) of the analytes in psychotic patients' plasma. PMID- 17340085 TI - Bioanalytical device based on cholesterol oxidase-bonded SAM-modified electrodes. AB - A rapid, simple and reproducible two-step method for constructing cholesterol biosensors by covalently bonding cholesterol oxidase (ChOx) to a 3,3' dithiodipropionic acid di(N-succinimidyl ester) (DTSP)-modified gold electrode is described. Exhaustive characterizations of both the immobilization process and the morphological properties of the resulting ChOx monolayer were performed via a quartz crystal microbalance (QCM) and atomic force microscopy (AFM) operated under liquid conditions, respectively. In addition, scanning electrochemical microscopy (SECM) measurements were performed in order to check that the immobilized enzyme retains its catalytic activity. The replacement of the natural electron acceptor (O(2)) in the enzymatic reaction with an artificial mediator, hydroxymethylferrocene (HMF), was also studied. Finally, cholesterol was amperometrically determined by measuring the hydrogen peroxide produced during the enzymatic reaction at +0.5 V. The optimized cholesterol biosensor exhibited a sensitivity of 54 nA mM(-1) and a detection limit of 22 microM. PMID- 17340086 TI - Vibrational overtone combination spectroscopy (VOCSY)-a new way of using IR and NIR data. AB - This work explores a novel method for rearranging 1st order (one-way) infra-red (IR) and/or near infra-red (NIR) ordinary spectra into a representation suitable for multi-way modelling and analysis. The method is based on the fact that the fundamental IR absorption and the first, second, and consecutive overtones of NIR absorptions represent identical chemical information. It is therefore possible to rearrange these overtone regions of the vectors comprising an IR and NIR spectrum into a matrix where the fundamental, 1st, 2nd, and consecutive overtones of the spectrum are arranged as either rows or columns in a matrix, resulting in a true three-way tensor of data for several samples. This tensorization facilitates explorative analysis and modelling with multi-way methods, for example parallel factor analysis (PARAFAC), N-way partial least squares (N-PLS), and Tucker models. The vibrational overtone combination spectroscopy (VOCSY) arrangement is shown to benefit from the "order advantage", producing more robust, stable, and interpretable models than, for example, the traditional PLS modelling method. The proposed method also opens the field of NIR for true peak decomposition--a feature unique to the method because the latent factors acquired using PARAFAC can represent pure spectral components whereas latent factors in principal component analysis (PCA) and PLS usually do not. PMID- 17340087 TI - Nuclear magnetic resonance of mass-limited samples using small RF coils. AB - Figure Schematic diagram of a typical arrangement used for hyphenating chemical microseparations (e.g. capillary HPLC, CE, or CEC) with microcoil NMR detection. PMID- 17340088 TI - Microwave-assisted extraction (MAE) for the determination of polybrominated diphenylethers (PBDEs) in sewage sludge. AB - An efficient microwave-assisted extraction (MAE) method has been developed and evaluated for the quantification of eight major polybrominated diphenylethers (PBDEs) in sewage sludge. The PBDEs were extracted from wet and dry sludge in a microwave extraction unit using a hexane/acetone mixture for 35 min at a controlled temperature of 130 degrees C. The extract was concentrated, cleaned up on a silica gel column, and analyzed by gas chromatography/mass spectrometry (GC/MS) in the negative chemical ionization (NCI) mode. The MAE procedure exhibited higher extraction efficiency, specifically for BDE (brominated diphenylether) 209, than the conventional Soxhlet extraction. The test congeners were clearly separated under specific instrumental operating conditions, at a source temperature of 230 degrees C and a column length of 20 m. The present analytical method showed recovery efficiencies ranging from 80 to 110% when applied to the PBDE-free sludge spiked with eight PBDE congeners. The efficiency of the MAE method was confirmed using sludge obtained from four sewage treatment plants (STPs). The results indicate that BDE 47, 99, and 209 are the most abundant congeners present in these sewage sludges, which is consistent with previous reports. PMID- 17340089 TI - Determination of iprodione in agrochemicals by infrared and Raman spectrometry. AB - Two methodologies based on vibrational spectrometry--making use of Fourier transform infrared absorption (FTIR) and Raman spectrometry--were developed for iprodione determination in solid pesticide formulations. The FTIR procedure involved the extraction of iprodione by CHCl(3), and the latter determination involved measuring the peak area between 1450 and 1440 cm(-1), corrected using a horizontal baseline defined at 1481 cm(-1). FT-Raman determination was performed directly on the powdered solid products, using standard chromatography glass vials as sample cells and measuring the Raman intensity between 1003 and 993 cm( 1), with a two-point baseline correction established between 1012 and 981 cm(-1). The sensitivities obtained were 0.319 area values g mg(-1) for FTIR determination and 5.58 area values g g(-1) for FT-Raman. The repeatabilities, taken to be the relative standard deviation of five independent measurements at 1.51 mg g(-1) and 10.98% w/w concentration levels, were equal to 0.16% and 0.9% for FTIR and FT Raman, respectively, and the limits of detection were 0.3 and 0.2% w/w (higher than those obtained for HPLC, 0.016% w/w). FTIR determination provided a sample frequency of 60 h(-1), higher than those obtained for the Raman and reference chromatography methods (25 and 8.6 h(-1), respectively). On the other hand, the new FT-Raman method eliminates reagent consumption and waste generation, and reduces the need for sample handling and the contact of operator with the pesticide. In spite of their lack of sensitivity, vibrational procedures can therefore provide viable environmentally friendly alternatives to laborious, time and solvent-consuming reference chromatography methods for quality control in commercially available pesticide formulations. PMID- 17340090 TI - A study of the interactions between carboplatin and blood plasma proteins using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry. AB - To study the carboplatin-protein interaction, a sensitive method using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry (SEC-ICP-MS) was developed. The complexes formed between plasma proteins and carboplatin were monitored and identified with this method. Composite blood plasma samples from patients who were undergoing chemotherapy were analyzed, and carboplatin was found to bind plasma proteins. In addition, blank plasma samples were spiked with carboplatin and were analyzed as a time course study, and the results confirmed that carboplatin formed complexes with plasma proteins, primarily albumin and gamma-globulin. To further substantiate the study, these two proteins were incubated with carboplatin. The binding between carboplatin and these proteins was then characterized qualitatively and quantitatively. In addition to a one-to-one binding of Pt to protein, protein aggregation was observed. The kinetics of the binding process of carboplatin to albumin and gamma globulin was also studied. The initial reaction rate constant of carboplatin binding to albumin was determined to be 0.74 M(-1) min(-1), while that for gamma globulin was 1.01 M(-1) min(-1), which are both lower than the rate constant of the cisplatin-albumin reaction previously reported. PMID- 17340091 TI - [The current diagnostic approach for chronic progressive dementia]. AB - This review presents diagnostic criteria for the different dementia syndromes and mild cognitive impairment. It is being claimed that in view of the current pharmacological interventions and after exclusion of symptomatic dementia, a controlled trial with cholinesterase inhibitors or memantine is more efficient than elaborate diagnostics. Efficiency of differential diagnosis will increase when drugs are available that specifically improve the different degenerative dementias and vascular dementia. Clinical pictures of the various dementia syndromes are briefly described. PMID- 17340093 TI - The cauliflower mosaic virus (CaMV) 35S promoter sequence alters the level and patterns of activity of adjacent tissue- and organ-specific gene promoters. AB - Here we report the effect of the 35S promoter sequence on activities of the tissue- and organ-specific gene promoters in tobacco plants. In the absence of the 35S promoter sequence the AAP2 promoter is active only in vascular tissues as indicated by expression of the AAP2:GUS gene. With the 35S promoter sequence in the same T-plasmid, transgenic plants exhibit twofold to fivefold increase in AAP2 promoter activity and the promoter becomes active in all tissue types. Transgenic plants hosting the ovary-specific AGL5:iaaM gene (iaaM coding an auxin biosynthetic gene) showed a wild-type phenotype except production of seedless fruits, whereas plants hosting the AGL5:iaaM gene along with the 35S promoter sequence showed drastic morphological alterations. RT-PCR analysis confirms that the phenotype was caused by activation of the AGL5:iaaM gene in non-ovary organs including roots, stems and flowers. When the pollen-, ovule- and early embryo specific PAB5:barnase gene (barnase coding a RNase gene) was transformed, the presence of 35S promoter sequence drastically reduced transformation efficiencies. However, the transformation efficiencies were restored in the absence of 35S promoter, indicating that the 35S promoter might activate the expression of PAB5:barnase in non-reproductive organs such as calli and shoot primordia. Furthermore, if the 35S promoter sequence was replaced with the NOS promoter sequence, no alteration in AAP2, AGL5 or PAB5 promoter activities was observed. Our results demonstrate that the 35S promoter sequence can convert an adjacent tissue- and organ-specific gene promoter into a globally active promoter. PMID- 17340092 TI - Arabidopsis thaliana plants expressing human beta-defensin-2 are more resistant to fungal attack: functional homology between plant and human defensins. AB - Human beta-defensin-2 (hBD-2) is a small antimicrobial peptide with potent activity against different Gram-negative bacteria and fungal/yeast species. Since human beta-defensins and plant defensins share structural homology, we set out to analyse whether there also exists a functional homology between these defensins of different eukaryotic kingdoms. To this end, we constructed a plant transformation vector harbouring the hBD-2 coding sequence, which we transformed to Arabidopsis thaliana plants, giving rise to A. thaliana plants indeed expressing hBD-2. Furthermore, we could demonstrate that this heterologously produced hBD-2 possesses antifungal activity in vitro. Finally, we could show that hBD-2 expressing A. thaliana plants are more resistant against the broad spectrum fungal pathogen Botrytis cinerea as compared to untransformed A. thaliana plants, and that this resistance is correlated with the level of active hBD-2 produced in these transgenic plants. Hence, we demonstrated a functional homology, next to the already known structural homology, between defensins originating from different eukaryotic kingdoms. To our knowledge, this is the first time that this is specifically demonstrated for plant and mammalian defensins. PMID- 17340094 TI - Evaluation of a novel Wave Bioreactor cellbag for aerobic yeast cultivation. AB - The Wave Bioreactor is widely used in cell culture due to the benefits of disposable technology and ease of use. A novel cellbag was developed featuring a frit sparger to increase the system's oxygen transfer. The purpose of this work was to evaluate the sparged cellbag for yeast cultivation. Oxygen mass transfer studies were conducted in simulated culture medium and the sparged system's maximum oxygen mass transfer coefficient (kLa) was 38 h(-1). These measurements revealed that the sparger was ineffective in increasing the oxygen transfer capacity. Cultures of Saccharomyces cerevisiae were successfully grown in oxygen blended sparged and oxygen-blended standard cellbags. Under steady state conditions for both cellbag designs, kLa values as high as 60 h(-1) were obtained with no difference in growth characteristics. This is the first report of a successful cultivation of a microbe in a Wave Bioreactor comparing conventional seed expansion in shake flasks and stirred tank bioreactors. PMID- 17340095 TI - Mechanical and structural properties of in vitro neurofilament hydrogels. AB - Neurofilaments belong to the class of cytoskeletal intermediate filaments and are the predominant structural elements in axons. They are composed of a semiflexible backbone and highly charged anionic sidearms protruding from the surface of the filaments. Here, the rheology of in-vitro networks of neurofilaments purified from pig spinal cord was determined. The mechanical properties of these networks are qualitatively similar to other hydrogels of semiflexible polymers. The low deformation storage modulus G'(omega) showed a concentration (c) dependence of G' approximately c (1.3) that is consistent with a model for semiflexible networks, but was also observed for polyelectrolyte brushes. A terminal relaxation was not observed in the frequency range investigated (0.007-5 Hz), supporting the notion that sidearms act as cross-links hindering slip between filaments on a time scale of many minutes. The mesh size distribution of the network was measured by analysis of Brownian motion of embedded beads. The concentration dependence of the mesh size follows the same power law behaviour as found for F-actin networks, but shows a significantly wider distribution attributable to the smaller persistence length of neurofilaments. The attractive interaction between filaments is increased by addition of Al(3+) ions resulting in a reduction of the linear response regime from strains bigger than 80% to less than 30%. PMID- 17340096 TI - Fast exocytosis mediated by T- and L-type channels in chromaffin cells: distinct voltage-dependence but similar Ca2+ -dependence. AB - Expression, spatial distribution and specific roles of different Ca(2+) channels in stimulus-secretion coupling of chromaffin cells are intriguing issues still open to discussion. Most of the evidence supports a role of high-voltage activated (HVA) Ca(2+) channels (L-, N-, P/Q- and R-types) in the control of exocytosis: some suggesting a preferential coupling of specific Ca(2+) channel subunits with the secretory apparatus, others favoring the idea of a contribution to secretion proportional to the expression density and gating properties of Ca(2+) channels. In this work we review recent findings and bring new evidence in favor of the hypothesis that also the LVA (low-voltage-activated, T-type) Ca(2+) channels effectively control fast exocytosis near resting potential in adrenal chromaffin cells of adult rats. T-type channels recruited after long-term treatments with pCPT-cAMP (or chronic hypoxia) are shown to control exocytosis with the same efficacy of L-type channels, which are the dominant Ca(2+) channel types expressed in rodent chromaffin cells. A rigorous comparison of T- and L type channel properties shows that, although operating at different potentials and with different voltage-sensitivity, the two channels possess otherwise similar Ca(2+)-dependence of exocytosis, size and kinetics of depletion of the immediately releasable pool and mobilize vesicles of the same quantal size. Thus, T- and L-type channels are coupled with the same Ca(2+)-efficiency to the secretory apparatus and deplete the same number of vesicles ready for release. The major difference of the secretory signals controlled by the two channels appear to be the voltage range of operation, suggesting the idea that stressful conditions (hypoxia and persistent beta-adrenergic stimulation) can lower the threshold of cell excitability by recruiting new Ca(2+) channels and activate an additional source of catecholamine secretion. PMID- 17340097 TI - Effects of confinement on insulin amyloid fibrils formation. AB - Insulin, a 51-residue protein universally used in diabetes treatment, is known to produce amyloid fibrils at high temperature and acidic conditions. As for other amyloidogenic proteins, the mechanisms leading to nucleation and growth of insulin fibrils are still poorly understood. We here report a study of the fibrillation process for insulin confined in a suitable polymeric hydrogel, with the aim of ascertain the effects of a reduced protein mobility on the various phases of the process. The results indicate that, with respect to standard aqueous solutions, the fibrillation process is considerably slowed down at moderately high concentrations and entirely suppressed at low concentration. Moreover, the analysis of the initial stages of the fibrillation process in aqueous solutions revealed a large spatial heterogeneity, which is completely absent when the fibrillation is carried out in the hydrogel. We attribute this heterogeneity to the diffusion in solution of large amyloidal aggregates, which must be formed very fast compared to the average times for the whole sample. These findings are interpreted in the framework of recently suggested heterogeneous nucleation mechanisms. Moreover, they may be useful for the development of new insulin pharmaceutical formulations, more stable against adverse conditions. PMID- 17340098 TI - [Tissue engineering for articular cartilage repair improved by gene transfer. Current concepts]. AB - Cartilage tissue engineering is the creation of functional substitutes of native articular cartilage in bioreactors by attaching chondrogenic cells to polymer scaffolds. One limitation of tissue engineering is the delivery of regulatory signals to cells according to specific temporal and spatial patterns. Using gene transfer techniques, polypeptide growth factor genes such as the human insulin like growth factor I (IGF-I) gene can be transferred into chondrocytes. When these modified cells are used for cartilage tissue engineering, the resulting cartilaginous constructs have improved structural and functional characteristics compared to constructs based on nonmodified cells. The combination of cartilage tissue engineering with overexpression of potential therapeutic genes using gene transfer technologies provides a basis for the development of novel molecular therapies for the repair of cartilage defects. PMID- 17340099 TI - Quantitative trait loci for early plant vigour of maize grown in chilly environments. AB - Maize (Zea mays L.) is particularly sensitive to chilling in the early growth stages. The objective of this study was to determine quantitative trait loci (QTL) for early plant vigour of maize grown under cool and moderately warm conditions in Central Europe. A population of 720 doubled haploid (DH) lines was derived from a cross between two dent inbred lines contrasting in early vigour and were genotyped with 188 SSR markers. The DH lines per se and their testcrosses with a flint line were evaluated in field experiments across 11 environments in 2001 and 2002. Plants were harvested after six to eight leaves had been fully developed to assess fresh matter yield as a criterion of early vigour. Seven QTL were detected for line performance and ten QTL for testcross performance, explaining 64 and 49% of the genetic variance. Six out of seven QTL detected in the lines per se were also significant in their testcrosses. Significant QTL x environment interaction was observed, but no relationship existed between the size of the QTL effects and the mean temperature in the individual environment. The correlation between fresh matter yield and days to silking was non-significant, indicating that differences in early plant vigour were not simply caused by maturity differences. For three additional chilling related traits, leaf chlorosis, leaf purpling, and frost damage seven, six, and five QTL were detected, respectively. Three QTL for leaf chlorosis, two for leaf purpling, and two for frost damage co-localized with QTL for fresh matter yield. Results are considered as a reliable basis for further genetic, molecular, and physiological investigations. PMID- 17340100 TI - Imaging readouts as biomarkers or surrogate parameters for the assessment of therapeutic interventions. AB - Surrogate markers and biomarkers based on imaging readouts providing predictive information on clinical outcome are of increasing importance in the preclinical and clinical evaluation of novel therapies. They are primarily used in studies designed to establish evidence that the therapeutic principle is valid in a representative patient population or in an individual. A critical step in the development of (imaging) surrogates is validation: correlation with established clinical endpoints must be demonstrated. Biomarkers must not fulfill such stringent validation criteria; however, they should provide insight into mechanistic aspects of the therapeutic intervention (proof-of-mechanism) or document therapy efficacy with prognostic quality with regard to the long-term clinical outcome (proof of concept). Currently used imaging biomarkers provide structural, physiological and metabolic information. Novel imaging approaches annotate structure with molecular signatures that are tightly linked to the pathophysiology or to the therapeutic principle. These cellular and molecular imaging methods yield information on drug biodistribution, receptor expression and occupancy, and/or intra- and intercellular signaling. The design of novel target-specific imaging probes is closely related to the development of the therapeutic agents and should be considered early in the discovery phase. Significant technical and regulatory hurdles have to be overcome to foster the use of imaging biomarkers for clinical drug evaluation. PMID- 17340101 TI - Regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE). AB - The aim of the present study was a detailed analysis of the regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE) by means of functional magnetic resonance imaging (MRI). A group of 26 patients with SAE and a group of 16 age-matched healthy volunteers were examined. Using a well-established dynamic susceptibility contrast-enhanced MRI method, the regional cerebral blood flow (rCBF) and blood volume (rCBV) were quantified for each subject in 12 different regions in the brain parenchyma. As compared to healthy volunteers, patients with SAE showed significantly reduced rCBF and rCBV values in white matter regions and in the occipital cortex. Regions containing predominantly grey matter show almost normal rCBF and rCBV values. In conclusion, quantitative analysis of rCBF and rCBV values demonstrates clearly that SAE is a disease that is associated with a reduced microcirculation predominantly in white matter. PMID- 17340102 TI - (1)H MR spectroscopic imaging in patients with MRI-negative extratemporal epilepsy: correlation with ictal onset zone and histopathology. AB - Proton magnetic resonance spectroscopy ((1)H MRS) is beneficial in the lateralization of the epileptogenic zone in temporal lobe epilepsy; however, its role in extratemporal and, especially, MRI-negative epilepsy has not been established. This study seeks to verify how (1)H MRS could help in localizing the epileptogenic zone in patients with MRI-negative extratemporal epilepsy. Seven patients (8-23 years) with MRI-negative refractory focal epilepsy were studied using (1)H MRS on a 1.5T MR system. Chemical shift imaging sequence in the transversal plane was directed towards the suspected epileptogenic zone localized by seizure semiology, scalp video/EEG, ictal SPECT and (18)FDG-PET. Spectra were evaluated using the program CULICH, and the coefficient of asymmetry was used for quantitative lateralization. MRS detected lateralization in all patients and was able to localize pathology in five. The most frequent findings were decreased ratios of N-acetylaspartate to choline compounds characterized by increasing choline concentration. The localization of the (1)H MRS abnormality correlated well with ictal SPECT and subdural mapping. In all cases, histopathological analysis revealed MRI-undetected focal cortical dysplasias. (1)H MRS could be more sensitive for the detection of discrete malformations of cortical development than conventional MRI. It is valuable in the presurgical evaluation of patients without MRI-apparent lesions. PMID- 17340103 TI - Acute bone marrow edema of the hip: role of MR imaging. AB - Acute bone marrow edema of the hip is a diagnostic challenge for both radiologists and clinicians. Marrow edema is often seen in patients with hip pain and restriction of motion. In patients with acute non-traumatic hip pain, whose radiographs are negative or inconclusive, MR imaging is the imaging study of choice. MR imaging is the most sensitive and specific imaging technique for detecting transient osteoporosis and osteonecrosis, as well as for detecting and staging fractures and microfractures. MR imaging is able to show marrow involvement in various inflammatory disorders and to diagnose reactive marrow edema from femoroacetabular impingment and greater trochanteric pain syndrome. In patients with septic arthritis, it may also depict associated marrow edema and suggest its reactive or infectious origin. For the neoplastic disorders, although plain radiographs should be the initial examination, MR imaging may follow for assessing extension to the surrounding soft tissues and/or associated pathologic fracture, facilitating thus the treatment planning. Computed tomography is more accurate compared with MR imaging in diagnosing intra-articular osteoid osteomas. PMID- 17340104 TI - Direct visualization of perforation sites in patients with a non-traumatic free pneumoperitoneum: added diagnostic value of thin transverse slices and coronal and sagittal reformations for multi-detector CT. AB - The incremental diagnostic value of adding 1.25-mm slices and coronal and sagittal reformatting to 5-mm axial reconstructions for direct visualization of the perforation site in patients with non-traumatic free pneumoperitoneum was assessed. Forty patients with non-traumatic bowel perforation and free pneumoperitoneum underwent computed tomography (CT). The perforation was gastroduodenal in 18 patients and involved the small or large bowel in 22 patients. Transverse scans were reconstructed with 5-mm thick sections at 5-mm intervals and 1.25-mm-thick sections at 1.25-mm intervals. The second data set was reformatted coronally and sagittaly with 3-mm-thick sections at 3-mm intervals. Three independent blinded readers interpreted 5-mm transverse scans, then combined 1.25-mm and 5-mm-transverse scans, and then combined transverse, coronal and sagittal scans. The rate of identification of the perforation site ranged from 43% to 53% with the combined axial, sagittal and coronal scans, from 28% to 48% with the 1.25- and 5-mm transverse scans, and from 5% to 20% only with the 5-mm thick transverse scans. The agreement between readers was significantly higher with thin slices and reformatting. The use of 1.25-mm axial slices and reformations intrinsically contained more useful diagnostic information than 5-mm axial slices alone for diagnosis of the perforation site in patients with pneumoperitoneum. PMID- 17340105 TI - Detecting endoleaks after endovascular AAA repair with a minimally invasive, implantable, telemetric pressure sensor: an in vitro study. AB - A feasibility study on a completely digital telemetric pressure sensor (TPS) to detect endoleaks was performed in an in vitro model of an abdominal aortic aneurysm (AAA). An endovascular-stented AAA silicone model with different types (I-III) and sizes (3-11 French) of endoleaks was created and pulsatile pressure was applied with physiological flow and pressure rates [mean intraaortic pressure (IAP): 95-130 mmHg] and different degrees of thrombosis of the aneurysm sac. Aneurysm sac pressure (ASP) was measured with the TPS and with wired pressure sensors (WPS) as a reference. Statistical analysis included paired t-test, Pearson's correlation analysis and Bland-Altman plots. After opening an endoleak, the mean ASP increased significantly (P < 0.0001) from 15 to almost 95% of the mean IAP depending on endoleak type and size. ASP could be measured accurately with the TPS and the WPS. The telemetric and wired ASP increase showed a high Pearson's correlation coefficient (r) for a non-thrombosed (r = 0.97) and a thrombosed (r = 0.96) aneurysm sac. In an in vitro silicone model, the newly designed telemetric pressure sensor was able to detect the occurrence of an endoleak in a non-invasive way and might be a valuable device for follow-up of endovascular AAA repair. PMID- 17340106 TI - No anticipation-no action: the role of anticipation in action and perception. AB - This paper reviews psychophysical evidence for the existence and the nature of two types of anticipation in goal-oriented action. The first one relates to attained changes of the perceptual world, thus to action goals. These anticipations determine appropriate motor output. We argue that goal codes do not only serve as a reference unit, against which currently produced behavioral effects are compared. Rather voluntary actions appear to be planned literally in terms of intended behavioral effects. The second type of anticipation relates to the environmental conditions that have to be met to bring an intended effect into being. These anticipations serve to trigger selected actions, when appropriate execution conditions are encountered. Altogether, the behavioral evidence portrays a remarkable automaticity of goal-oriented action. Once a goal exists (wherever it might come from), corresponding efferent output is generated and executed under appropriate conditions. PMID- 17340107 TI - Strategies to unravel the function of orphan biosynthesis pathways: recent examples and future prospects. AB - The recent increase and availability of whole genome sequences have revised our view of the metabolic capabilities of microorganisms. From these data, a large number of orphan biosynthesis pathways have been identified by bio-informatics. Orphan biosynthetic pathways are gene clusters for which the encoded natural product is unknown. It is worthy to note that the number of orphan pathways coding for putative natural products outnumbers by far the number of currently known metabolites for a given organism. Whilst Streptomyces coelicolor was known to produce only 4 secondary metabolites, the genome analysis revealed 18 additional orphan biosynthetic pathways. It is intriguing to note that this is not a particular case because analysis of other microbial genomes originating from myxobacteria, cyanobacteria and filamentous fungi showed the presence of a comparable or even larger number of orphan pathways. The discovery of these numerous pathways represents a treasure trove, which is likely to grow exponentially in the future, uncovering many novel and possibly bio-active compounds. The few natural products that have been correlated with their orphan pathway are merely the tip of the iceberg, whilst plenty of metabolites await discovery. The recent strategies and methods to access these promising hidden natural products are discussed in this review. PMID- 17340108 TI - Unique butyric acid incorporation patterns for salinosporamides A and B reveal distinct biosynthetic origins. AB - Feeding sodium butyrate (0.25-1 mg/ml) to cultures of Salinispora tropica NPS21184 enhanced the production of salinosporamide B (NPI-0047) by 319% while inhibiting the production of salinosporamide A (NPI-0052) by 26%. Liquid chromatography mass spectrometry analysis of the crude extract from the strain NPS21184 fed with 0.5 mg/ml sodium [U-(13)C(4)]butyrate indicated that butyrate was incorporated as a contiguous four-carbon unit into NPI-0047 but not into NPI 0052. Nuclear magnetic resonance analysis of NPI-0047 and NPI-0052 purified from the sodium [U-(13)C(4)]butyrate-supplemented culture extract confirmed this incorporation pattern. The above finding is the first direct evidence to demonstrate that the biosynthesis of NPI-0047 is different from NPI-0052, and NPI 0047 is not a precursor of NPI-0052. PMID- 17340109 TI - A unique beta-agarase, AgaA, from a marine bacterium, Vibrio sp. strain PO-303. AB - The agaA gene encoding beta-agarase-a (AgaA) was cloned from the chromosomal DNA of a marine bacterium, Vibrio sp. strain PO-303. The nucleotide sequence of the agaA gene consists of 2,958 bp and encodes a protein of 985 amino acids with a molecular mass of 106,062 Da. The deduced enzyme protein contains a typical N terminal signal peptide of 29 amino acid residues, followed by a 266 amino acid sequence that is homologous to catalytic module of family 16 glycoside hydrolases, a bacterial immunoglobulin group 2 (Big-2)-like domain of 52 amino acid residues, two carbohydrate-binding modules of family 6 separated from Big-2 like domain by nine times repeated GDDTDP amino acid sequence. AgaA is the first agarase that was identified to possess a Big-2-like domain. The recombinant AgaA (rAgaA) expressed in Escherichia coli exhibited maximal activity around 40 degrees C and pH 7.5, with a specific activity of 16.4 units mg(-1), a K (m) of 1.10 mg ml(-1), and a V (max) of 22.5 micromol min(-1) mg(-1) for agarose. The rAgaA hydrolyzed neoagarohexaose, but did not act on neoagarotetraose and neoagarobiose. PMID- 17340110 TI - Modeling the adsorption of aromatic compounds on the TiO2/SiO2 catalyst. AB - The Grand Canonical Monte Carlo method was used to analyse the phenomenon of adsorption of aromatic compounds (i.e. phenol, toluene, benzoic acid and salicylic acid) on the surface of the titania-silica (TiO2/SiO2) catalyst. We found that different types of interactions play important roles in the adsorption of molecules having polar and non-polar groups. Moreover, we found that the interactions between sorbate molecules are strong, and are the cause of multilayer adsorption occurring in the investigated temperature and pressure range. PMID- 17340111 TI - Theoretical analysis of the effects of guanine oxidative damage on the properties of B-DNA telomere fragments. AB - The molecular dynamics as well as ab initio MP2/6-31G(d = 0.25) single point calculations were performed for native and oxidized B-DNA telomeric fragments. The structural, dynamic, energetic and electrostatic properties along with frontier orbitals distribution were described for the central triad consisting of three guanine molecules in its canonical or oxidized forms. Although the average structural parameters characterizing all of the studied telomere fragments are close each to other, the significant consequence on angular and displacement flexibilities are observed. Namely, the increase of mutual displacement of two successive base pairs along either axis and increase of the rotation of two bases of opposite strand are main dynamic consequences of presence of 8-oxo-guanine in the central triad of telomeric B-DNA. Besides, the significant increase of stacking energies in case of 8-oxo-guanine were found. Furthermore, the guanine pattern visible from the major groove may be described as donor-acceptor-acceptor formed by H8-N7-O6 atoms, respectively. To the contrary the presence of 8-oxo guanine changes the electrostatic properties of the major groove into acceptor donor-acceptor coming from O8-H7-O6 atoms. This results in significant alteration of ESP characteristics. Finally, the molecular orbital properties are also significantly affected by oxidation of telomeric B-DNA fragments. All these factors contribute to decrease of binding of telomere proteins. PMID- 17340112 TI - Analysis of the differences in the folding mechanisms of c-type lysozymes based on contact maps constructed with interresidue average distances. AB - A method for analyzing differences in the folding mechanisms of proteins in the same family is presented. Using only information from the amino acid sequences, contact maps derived from the interresidue average distances are employed. These maps, referred to as average distance maps (ADM), are applied to the folding of c type lysozymes. The results reveal that the ADMs of these lysozymes reflect the differences in the detailed folding mechanisms. Further possible applications of the present method are also discussed. PMID- 17340113 TI - Molecular docking study of the binding of aminopyridines within the K+ channel. AB - We present a molecular docking study aimed to identify the binding site of protonated aminopyridines for the blocking of voltage dependent K(+) channels. Several active aminopyridines are considered: 2-aminopyridine, 3-aminopyridine, 4 aminopyridine, 3,4-diaminopyridine, and 4-aminoquinoleine. We apply the AutoDock force field with a lamarckian genetic algorithm, using atomic charges for the ligands derived from the electrostatic potential obtained at the B3LYP/cc-pVDZ level. We find a zone in the alpha-subunit of the K(+) channel bearing common binding sites. This zone corresponds to five amino acids comprised between residuals Thr107 and Ala111, in the KcsA K(+) channel (1J95 pdb structure). The 2 aminopyridine, 3-aminopyridine, 4-aminopyridine, and 3,4-diaminopyridine bind to the carboxylic oxygens of Thr107 and Ala111. In all cases aminopyridines are perpendicular to the axis of the pore. 4-aminoquinoleine binds to the carboxylic oxygen of Ala111. Due to its large size, the molecular plane is parallel to the axis of the pore. The charge distributions and the structures of the binding complexes suggest that the interaction is driven by formation of several hydrogen bonds. We find 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, and 3,4 diaminopyridine with similar binding energy. Considering the standard error of the estimate of the AutoDock force field, this energy should lie, as a rough estimation, in the interval 3-7 kcal mol(-1). On the other hand, 4 aminoquinoleine seems to have a smaller binding energy. PMID- 17340114 TI - A quantitative structure-property relationship study for refractive indices of conjugated polymers. AB - The quantitative structure-property relationship (QSPR) study was performed between descriptors representing the molecular structures and refractive indices for a set of 35 pi-conjugated polymers. A seven-descriptor correlation was developed for the prediction of refractive indices with R = 0.936 and s = 0.028 by stepwise multilinear regression analysis. The average relative error for the calculation of refractive indices was 1.022%. The stability of the proposed model was validated using leave-one-out cross-validation and randomization experiments. Since the model requires only molecular descriptors derived solely from the repeating unit structures of conjugated polymers, it has better predictive capability comparing with the existing group-contribution methods. PMID- 17340115 TI - Phenolic esters with potential anticancer activity--the structural variable. AB - The conformational preferences of several potential anticancer dihydroxycinnamic esters with a variable length alkyl chain were studied by quantum-mechanical (DFT) calculations (both for the isolated molecule and for aqueous solutions). The orientation of the hydroxyl ring substituents and of the alkyl ester moiety relative to the carbonyl group showed these to be the most determinant factors for the overall stability of this type of phenolic systems, strongly dependent on an effective pi-electron delocalization. Compared to the parent caffeic acid (dihydroxycinnamic acid), esterification was found to lead to a higher conformational freedom, and to affect mainly the energy barrier corresponding to the (O=)C-OR internal rotation. No particular differences were verified to occur upon lengthening of the ester alkyl chain, except when this is branched instead of linear. The vibrational spectra of the whole series of compounds were simulated, based on their calculated harmonic vibrational frequencies, and a preliminary assignment was performed. PMID- 17340116 TI - Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats. AB - RATIONALE: Neurodevelopmental deficits of parvalbumin-immunoreactive gamma aminobutyric acid (GABA)ergic interneurons in prefrontal cortex have been reported in schizophrenia. Glutamate influences the proliferation of this type of interneuron by an N-methyl-D-aspartate (NMDA)-receptor-mediated mechanism. The present study hypothesized that prenatal blockade of NMDA receptors would disrupt GABAergic neurodevelopment, resulting in differences in effects on behavioral responses to a noncompetitive NMDA antagonist, phencyclidine (PCP), and a dopamine releaser, methamphetamine (METH). METHODS: GABAergic neurons were immunohistochemically stained with parvalbumin antibody. Psychostimulant-induced hyperlocomotion was measured using an infrared sensor. RESULTS: Prenatal exposure (E15-E18) to the NMDA receptor antagonist MK-801 reduced the density of parvalbumin-immunoreactive neurons in rat medial prefrontal cortex on postnatal day 63 (P63) and enhanced PCP-induced hyperlocomotion but not the acute effects of METH on P63 or the development of behavioral sensitization. Prenatal exposure to MK-801 reduced the number of parvalbumin-immunoreactive neurons even on postnatal day 35 (P35) and did not enhance PCP-induced hyperlocomotion, the acute effects of METH on P35, or the development of behavioral sensitization to METH. CONCLUSIONS: These findings suggest that prenatal blockade of NMDA receptors disrupts GABAergic neurodevelopment in medial prefrontal cortex, and that this disruption of GABAergic development may be related to the enhancement of the locomotion-inducing effect of PCP in postpubertal but not juvenile offspring. GABAergic deficit is unrelated to the effects of METH. This GABAergic neurodevelopmental disruption and the enhanced PCP-induced hyperlocomotion in adult offspring prenatally exposed to MK-801 may prove useful as a new model of the neurodevelopmental process of pathogenesis of treatment-resistant schizophrenia via an NMDA-receptor-mediated hypoglutamatergic mechanism. PMID- 17340117 TI - Sex, age, spleen size, and kidney fat of red deer relative to infection intensities of the lungworm Elaphostrongylus cervi. AB - We analyzed the relationships among spleen size, body condition (measured as kidney fat), and larval counts of the nematode Elaphostrongylus cervi in red deer (Cervus elaphus). The aim was to investigate the interaction between host body condition and intensity of infection with parasites. As red deer are highly polygynous, we also tested whether these relationships varied with sex and age of the hosts. Kidney fat and spleen size were positively correlated in subadults (2 3 years old) and adults (>3 years old), but not in calves (<1 year old) or yearlings (1-2 years old). Spleen size was negatively associated with nematode load in subadult females and in adult males. These two age classes are potentially the most nutritionally stressed, as subadult hinds are still growing and often engaging in rearing their first calf, and adult stags were sampled just after the rut, which is recognized as a substantial energy drain in this age-sex class, as they compete to hold females during the mating season. Body condition related negatively to parasite count only in adult males. In the context of red deer life history, these findings suggest that spleen size is dependent on body condition and that it could be affected by variation in resource partitioning among immune defense, growth, and reproductive effort in red deer. For the first time in a wild mammal, the spleen mass is shown to be positively related to body condition and negatively related to parasite infection. We conclude that elucidating whether spleen mass reflects immune defense investment or a measure of general body condition should contribute to understanding topical issues in mammal ecology. PMID- 17340118 TI - Cladistic biogeographic analysis suggests an early Caribbean diversification in Mexico. AB - The Great American Biotic Interchange has been the predominant paradigm for explaining biotic diversification in the Nearctic/Neotropical overlap or Mexican Transition Zone, which is commonly explained by the collision of the North and South American continental plates, which began in the Oligocene and fused both landmasses. In the most far-reaching cladistic biogeographical analysis of the area to date, evidence has been found supporting the existence of a remnant Caribbean region extending from eastern Mexico to southeastern USA, a hypothesis that challenges current views of the Great American Biotic Interchange and the Mexican Transition Zone. We show herein that an older terrane, which has drifted to the present day positions of Yucatan and Cuba, may be biogeographically linked to an early 'Gondwanan' biota of the Paleocene (ca. 60 Ma). The evidence indicates an east-west biotic divide in Mexico, existing before the collision and formation of Central America. The south-north division of the country, previously recognized by several authors as associated with the Great American Biotic Interchange and the Mexican Transition Zone, is of a younger age. PMID- 17340119 TI - Effect of carbohydrates on the production of thaxtomin A by Streptomyces acidiscabies. AB - Several Streptomyces species cause plant diseases, including S. scabies, S. acidiscabies and S. turgidiscabies, which produce common scab of potato and similar diseases of root crops. These species produce thaxtomins, dipeptide phytotoxins that are responsible for disease symptoms. Thaxtomins are produced in vivo on diseased potato tissue and in vitro in oat-based culture media, but the regulation of thaxtomin biosynthesis is not understood. S. acidiscabies was grown in a variety of media to assess the impact of medium components on thaxtomin A (ThxA) production. ThxA biosynthesis was not correlated with bacterial biomass, nor was it stimulated by alpha-solanine or alpha-chaconine, the two most prevalent potato glycoalkaloids. ThxA production was stimulated by oat bran broth, even after exhaustive extraction, suggesting that specific carbohydrates may influence ThxA biosynthesis. Oat bran contains high levels of xylans and glucans, and both of these carbohydrates, as well as xylans from wheat and tamarind, stimulated ThxA production, but not to the same extent as oat bran. Starches and simple sugars did not induce ThxA production. The data indicate that complex carbohydrates may act as environmental signals to plant pathogenic Streptomyces, allowing production of thaxtomin and enabling bacteria to colonize its host. PMID- 17340120 TI - Arsenite induced oxidative damage in mouse liver is associated with increased cytokeratin 18 expression. AB - Cytokeratins (CK) constitute a family of cytoskeletal intermediate filament proteins that are typically expressed in epithelial cells. An abnormal structure and function are effects that are clearly related to liver diseases as non alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. We have previously observed that sodium arsenite (SA) induced the synthesis of CK18 protein and promotes a dose-related disruption of cytoplasmic CK18 filaments in a human hepatic cell line. Both abnormal gene expression and disturbance of structural organization are toxic effects that are likely to cause liver disease by interfering with normal hepatocyte function. To investigate if a disruption in the CK18 expression pattern is associated with arsenite liver damage, we investigated CK18 mRNA and protein levels in liver slices treated with low levels of SA. Organotypic cultures were incubated with 0.01, 1 and 10 microM of SA in the absence and presence of N-acetyl cysteine (NAC). Cell viability and inorganic arsenic metabolism were determined. Increased expression of CK18 was observed after exposure to SA. The addition of NAC impeded the oxidative effects of SA exposure, decreasing the production of thiobarbituric acid-reactive substances and significantly diminishing the up regulation of CK18 mRNA and protein. Liver arsenic levels correlated with increased levels of mRNA. Mice treated with intragastric single doses of 2.5 and 5 mg/kg of SA showed an increased expression of CK18. Results suggest that CK18 expression may be a sensible early biomarker of oxidative stress and damage induced by arsenite in vitro and in vivo. Then, during SA exposure, altered CK expression may compromise liver function. PMID- 17340121 TI - Gene expression analyses of the liver in rats treated with oxfendazole. AB - The effect of oxfendazole (OX), a benzimidazole anthelmintic, on hepatic gene expression was investigated in the liver of rats as a preliminary study to elucidate the possible mechanism of its non-genotoxic hepatocarcinogenesis. The liver from a male F344/N rat given a diet containing 500 ppm of OX for 3 weeks was examined by global gene expression analysis in comparison with an untreated rat. Microarray analysis revealed that phase I and phase II detoxifying enzymes were up-regulated in an OX-treated rat. In addition to these genes, the expressions of several upregulated genes related to xenobiotic metabolism and oxidative stress [e.g. Cyp1a1; NAD(P)H dehydrogenase, quinone 1 (Nqo1); glutathione peroxidase 2 (Gpx2); glutathione S-transferase Yc2 subunit (Yc2)], were confirmed by real-time reverse transcription polymerase chain reaction (RT PCR). Furthermore, rats were administered 500 or 1,000 ppm of OX for 9 weeks, and the effect of OX on oxidative stress responses was evaluated by real-time RT-PCR along with conventional toxicological assays, including lipid peroxidation (thiobarbituric acid-reactive substance; TBARS). A longer treatment period and/or a higher dose of OX tended to increase the gene expressions of not only phase I (Cyp1a1 and Cyp1a2) but also phase II (Nqo1, Gpx2, Yc2, and Akr7a3) drug metabolizing enzymes. Toxicological parameters, such as TBARS, serum aspartate aminotransferase (AST), and serum alkaline phosphatase (ALP), showed slight but significant increases after treatment with OX for 9 weeks. These results indicate that OX elicits adaptive responses against oxidative stress in the liver and suggest that the imbalance in redox status might be one of the factors triggering the initial step of OX-induced non-genotoxic carcinogenesis in the liver of rats. PMID- 17340122 TI - Hepatocytes isolated from preneoplastic rat livers are resistant to ethacrynic acid cytotoxicity. AB - Glutathione S-transferases (GSTs) are involved in the detoxification of xenobiotics, such as several cytostatic drugs, through conjugation with glutathione (GSH). Pi class GST (GST P) liver expression is associated with preneoplastic and neoplastic development and contributes with the drug-resistance phenotype. Ethacrynic acid (EA) is an inhibitor of rat and human GSTs. In addition, causes lipid peroxidation in isolated rat hepatocytes. Therefore, we decided to evaluate the role of the GST/GSH system in isolated hepatocytes from preneoplastic rat livers (IP) in the presence of EA and determine the cytotoxicity of the drug. Our results showed a resistance to the toxic effects of EA since viability and cellular integrity values were significantly higher than control. Initial levels of thiobarbituric acid reactive substances (TBARS) in IP hepatocytes were significantly higher than control and the presence of EA did not change TBARS levels. A diminution in intracellular total GSH was observed by treating with EA isolated hepatocytes from both groups. However, the initial total GSH levels were higher in IP hepatocytes than in control. Immunoblotting analysis showed the presence of GST P in IP animals only. Although alpha and mu class isoenzymes levels were decreased in IP hepatocytes, total GST activity was 1.5-fold higher than in control. In addition, multidrug-resistance protein 2 (Mrp2) showed fivefold decreased levels in IP hepatocytes. In conclusion, increased total GSH, decreased Mrp2 levels and the presence of GST P could be critical factors involved in the resistance of IP hepatocytes to the toxicity of EA. PMID- 17340123 TI - Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population. AB - AIMS/HYPOTHESIS: The transcription factor 7-like 2 gene (TCF7L2) has been shown to be strongly associated with an increased risk of type 2 diabetes in white populations. To further investigate the involvement of TCF7L2 in conferring susceptibility to type 2 diabetes, we examined the association of TCF7L2 polymorphisms with type 2 diabetes in a Japanese population. SUBJECTS AND METHODS: We analysed four SNPs (rs12255372, rs7903146, rs7901695 and rs11196205) and one tetranucleotide repeat polymorphism (DG10S478) in 1,630 Japanese subjects with type 2 diabetes and 1,064 control subjects. RESULTS: All investigated polymorphisms were significantly associated with type 2 diabetes, and rs12255372 showed the strongest association (T vs G, chi2 = 9.20, p = 0.0024, odds ratio = 1.70, 95% CI = 1.20-2.41), although the frequency of the risk allele in our population was much lower than that in white populations. The microsatellite polymorphism showed an almost complete linkage disequilibrium to rs1255372 when the alleles with longer repeats (+8, +12) were considered as minor alleles and showed an association with type 2 diabetes (chi2 = 5.34, p = 0.021, odds ratio = 1.50, 95% CI = 1.06-2.12). CONCLUSIONS/INTERPRETATION: These results indicate that TCF7L2 might be a strong candidate for conferring susceptibility to type 2 diabetes across different ethnicities. PMID- 17340124 TI - Threshold position control of arm movement with anticipatory increase in grip force. AB - The grip force holding an object between fingers usually increases before or simultaneously with arm movement thus preventing the object from sliding. We experimentally analyzed and simulated this anticipatory behavior based on the following notions. (1) To move the arm to a new position, the nervous system shifts the threshold position at which arm muscles begin to be recruited. Deviated from their activation thresholds, arm muscles generate activity and forces that tend to minimize this deviation by bringing the arm to a new position. (2) To produce a grip force, with or without arm motion, the nervous system changes the threshold configuration of the hand. This process defines a threshold (referent) aperture (R(a)) of appropriate fingers. The actual aperture (Q(a)) is constrained by the size of the object held between the fingers whereas, in referent position R(a), the fingers virtually penetrate the object. Deviated by the object from their thresholds of activation, hand muscles generate activity and grip forces in proportion to the gap between the Q(a) and R(a). Thus, grip force emerges since the object prevents the fingers from reaching the referent position. (3) From previous experiences, the system knows that objects tend to slide off the fingers when arm movements are made and, to prevent sliding, it starts narrowing the referent aperture simultaneously with or somewhat before the onset of changes in the referent arm position. (4) The interaction between the fingers and the object is accomplished via the elastic pads on the tips of fingers. The pads are compressed not only due to the grip force but also due to the tangential inertial force ("load") acting from the object on the pads along the arm trajectory. Compressed by the load force, the pads move back and forth in the gap between the finger bones and object, thus inevitably changing the normal component of the grip force, in synchrony with and in proportion to the load force. Based on these notions, we simulated experimental elbow movements and grip forces when subjects rapidly changed the elbow angle while holding an object between the index finger and the thumb. It is concluded that the anticipatory increase in the grip force with or without correlation with the tangential load during arm motion can be explained in neurophysiological and biomechanical terms without relying on programming of grip force based on an internal model. PMID- 17340125 TI - Comparative evaluation of active contour model extensions for automated cardiac MR image segmentation by regional error assessment. AB - OBJECTIVE: In the field of cardiac MR image segmentation, active contour models, or snakes have been extensively used, owing to their promising results and to the numerous extensions proposed to improve their performance. This paper explores a methodology for evaluating cardiac MR image segmentation algorithms, which assesses the distance between computer-generated and the observer's hand-outlined boundaries. This metric was applied to various external force extensions of the traditional snake, since no systematic comparison has been performed. MATERIALS AND METHODS: Cardiac MRI from six patients were analyzed. Imaging was performed on a 1.5 T MR scanner with ECG-gated balanced steady-state free precession (b SSFP) sequences. Segmentation performances were established for traditional snake, gradient vector flow snake, standard- and guided- pressure force-based snake. The use of a pre-treatment with non-linear anisotropic filtering was also compared to non-filtered images. RESULTS: Agreement between manual and segmentation algorithms was satisfactory for ejection fraction for every segmentation scheme. However end-systolic and end-diastolic volumes were systematically underestimated. CONCLUSION: The developed regional error metric provided a more rigorous evaluation of the segmentation schemes in comparison to the classical derived parameters based on left ventricle volume estimation, usually used in functional cardiac MR studies. These derived parameters can furthermore mask local segmentation errors. PMID- 17340126 TI - Smooth muscle mediates circumferential conduction of hyperpolarization and relaxation to focal endothelial cell activation in large coronary arteries. AB - Longitudinal conduction of endothelium-dependent vasodilatation is mediated by intercellular spread of hyperpolarization via gap junctions along the endothelium. If similar electrical signals from the endothelium conduct around the circumference of arteries via smooth muscle cells, then, both longitudinal and circumferential spread of such signals would make it possible for a wide annulus of a large blood vessel like an epicardial coronary artery to dilate to local stimuli. To examine this in vitro, we developed a dual-chambered organ bath in which both membrane potential and force are independently determined in endothelium-intact and -denuded regions of a single annulus of artery. Hyperpolarizations and relaxations to endothelium-dependent vasodilators like bradykinin (BK) and substance P in smooth muscle cells immediately beneath the local endothelium-intact region (local responses) are conducted via smooth muscle cells around the circumference of the artery. The local relaxation was partially inhibited by the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (L NOARG), and subsequently abolished by further treatment with a combination of two characteristic inhibitors of endothelium-dependent hyperpolarization-the Ca2+ activated potassium channel (KCa) channel inhibitors, apamin and charybdotoxin. The conducted hyperpolarizations and relaxations to BK were unaffected by L NOARG, but were abolished by apamin and charybdotoxin. In conclusion, these studies demonstrate for the first time that NO acts only as a local vasodilator, whereas endothelium-dependent hyperpolarization (EDH) causes local and remote vasodilatation in large coronary arteries. We propose that such a remote EDH dependent signalling mechanism compensates for the loss of the local NO-dependent vasodilatation in diseased arteries. PMID- 17340128 TI - Necrotizing fasciitis in the head and neck region: an analysis of standard treatment effectiveness. AB - A standard treatment procedure for necrotizing fasciitis in the head and neck region was introduced in 1999 at Rigshospitalet (National Hospital of Denmark) Copenhagen. The new procedure introduced more drastic surgical debridement than before, combined with a set antibiotic regime and intravenous gamma globulin and adjunctive hyperbaric oxygen treatment (HBO). To evaluate the effect of this, a retrospective study was undertaken, involving 19 patients treated for NF at the ENT department from 1996-2004. Between 1996 and 1999 eight patients were treated (non-HBO) from 1999-2004 eleven patients were treated (HBO group). Length of antibiotic treatment was very similar in the two groups (mean 22.5 days) as was bacteriology. Aetiological focus differed marginally with the HBO group showing a clear tendency towards odontogen focus. The HBO group was found to undergo significantly more debridement procedures (3.36). The most drastic difference in the two groups however, was the reduction in mortality. The non-HBO group had a mortality of 75% and in the HBO group they all survived. This obviously resulted in a prolonged hospital stay for the HBO group (mean 30.8 days). The study concluded that the reduction in mortality was due to the combined effects of the different entities in the new treatment guidelines. It was not possible to isolate a specific factor responsible for the change. PMID- 17340129 TI - Mastoid obliteration combined with soft-wall reconstruction of posterior ear canal. AB - To clarify the usefulness of modified soft-wall reconstruction method by combing with mastoid obliteration, 96 patients (98 ears) with their age ranging from 5 to 82 (average 51.3), including 62 ears with chronic otitis media (COM) with cholesteatoma, 18 ears with non-cholesteatomatous COM, 14 ears with postoperative cavity problem, and 4 ears with adhesive-type COM, who had soft-wall reconstruction of the posterior ear canal and mastoid obliteration using mainly bone powder following mastoidectomy, were evaluated their postoperative conditions more than a year after surgery. Overall success rate was 76.5% (75/98), and fresh cases showed better success rate (84.8%) than those with a history of multiple surgeries (69.2%). Among unsuccessful cases, crust and/or debris accumulation was observed most (nine ears), followed by persistent wet condition (seven ears), and exposure of the obliterated material (five ears), while only two ears showed a retraction pocket formation. The success rates remained almost the same among those who were followed for more than 2 and 3 years (46/61, 75% and 21/28, 75%, respectively). In 60 ears on which postoperative hearing was assessed, 41.7% showed less than 15 dB of air-bone gap (ABG), and 61.7% showed less than 20 dB of ABG. Mastoid obliteration with bone powder in combination with soft-wall reconstruction of the posterior ear canal appeared a useful method for obliterating mastoidectomized cavity especially for prevention of postoperative pocket formation. PMID- 17340127 TI - The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone. AB - This study characterized the pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, its metabolite, ADL 08-0011, and methylnaltrexone. The activities of the compounds were investigated with respect to human or guinea pig opioid receptor binding and function in recombinant cell lines and mechanical responsiveness of the guinea pig ileum. Alvimopan and ADL 08 0011 had higher binding affinity than methylnaltrexone at human mu opioid receptors (pK (i) values of 9.6, 9.6, and 8.0, respectively). The compounds had different selectivities for the mu receptor over human delta and guinea pig kappa opioid receptors. ADL 08-0011 had the highest mu receptor selectivity. With respect to their mu opioid receptor functional activity ([(35)S]GTPgammaS incorporation), methylnaltrexone had a positive intrinsic activity, consistent with partial agonism, unlike alvimopan and ADL 08-0011, which had negative intrinsic activities. Alvimopan, ADL 08-0011, and methylnaltrexone antagonized inhibitory responses mediated by the mu opioid agonist, endomorphin-1 (pA (2) values of 9.6, 9.4, and 7.6, respectively) and by U69593, a kappa opioid agonist (pA (2) values of 8.4, 7.2, and 6.7, respectively). In morphine-naive guinea pig ileum, methylnaltrexone reduced, while alvimopan and ADL 08-0011 increased, the amplitude of electrically evoked contractions and spontaneous mechanical activity. In tissue from morphine-dependent animals, alvimopan and ADL 08-0011 increased spontaneous activity to a greater degree than methylnaltrexone. The data suggested that alvimopan-induced contractions resulted predominantly from an interaction with kappa opioid receptors. It is concluded that alvimopan, ADL 08 0011, and methylnaltrexone differ in their in vitro pharmacological properties, particularly with respect to opioid receptor subtype selectivity and intrinsic activity. The clinical significance of the data from this study remains to be determined. PMID- 17340130 TI - Hyperbaric oxygen and steroid therapy for idiopathic sudden sensorineural hearing loss. AB - In our controlled retrospective analysis of medical records in tertiary care academic medical center, we aimed to investigate the therapeutic effects of hyperbaric oxygen (HBO) therapy combined with steroid administration for idiopathic sudden sensorineural hearing loss (ISSNHL) in comparison with that of steroid administration alone. Our subjects were 130 consecutive inpatients with ISSNHL (hearing levels >/=40 dB; time from the onset of hearing loss to the start of treatment /=80 dB, the hearing improvement rate was significantly higher in the HBO group than in the steroid group (51.1 +/- 7.0% vs. 27.1 +/- 7.8%; P < 0.05), while in patients whose initial hearing levels were <80 dB, hearing outcomes were not statistically different between the two groups. In both the HBO and steroid groups, patients with initial hearing levels of <80 dB showed a better hearing improvement rate than those with initial hearing levels of >/=80 dB. In conclusion HBO therapy shows a significant additional effect in combination with steroid therapy for ISSNHL, particularly in patients with severe hearing loss. PMID- 17340131 TI - Analysis of exon 2 of MTS1 in HPV-positive and HPV-negative tumors of the head and neck region. AB - The aim of this study was to investigate the role of human papillomaviruses (HPVs) and alterations of p16INK4A in different squamous cell carcinomas (SCCs) of the head and neck region by screening these carcinomas for alterations in exon 2 of p16INK4A and for HPV DNA. A total of 42 samples of different SCCs of the head and neck were collected by biopsy or surgical resection. After DNA isolation, exon 2 of p16 was amplified and sequenced. HPV DNA was detected by applying a broad-spectrum polymerase chain reaction system. Mutations were found in 4 of our 42 samples. A total of 27 biopsies showed the presence of HPV DNA. All of the biopsies showing a mutation in exon 2 of CDK4 were HPV-positive, except the first biopsy of an oropharyngeal carcinoma. It might be possible that HPV infection and mutations in the exon 2 of CDK4 play a causal role in malignant transformation in a small number of squamous carcinomas of the head and neck region. PMID- 17340132 TI - Involvement of autophagy in viral infections: antiviral function and subversion by viruses. AB - Autophagy is a cellular process involved in the degradation and turn-over of long lived proteins and organelles, which can be subjected to suppression or further induction in response to different stimuli. According to its essential role in cellular homeostasis, autophagy has been implicated in several pathologies including cancer, neurodegeneration and myopathies. More recently, autophagy has been described as a mechanism of both innate and adaptive immunity against intracellular bacteria and viruses. In this context, autophagy has been proposed as a protective mechanism against viral infection by degrading the pathogens into autolysosomes. This is strengthened by the fact that several proteins involved in interferon (IFN) signalling pathways are linked to autophagy regulation. However, several viruses have evolved strategies to divert IFN-mediated pathways and autophagy to their own benefit. This review provides an overview of the autophagic process and its involvement in the infection by different viral pathogens and of the connections existing between autophagy and proteins involved in IFN signalling pathways. PMID- 17340133 TI - Limited availability of L-arginine increases DNA-binding activity of NF-kappaB and contributes to regulation of iNOS expression. AB - The impact of nutrients on gene expression can be mediated by the availability of amino acids. The aim of this study is to examine the effect of limited availability of L: -arginine on the DNA-binding activity of NF-kappaB, a dominant transcription factor in inflammation, and the consequence for the expression pattern of inducible nitric oxide synthase (iNOS) in murine keratinocytes. Low availability of L: -arginine leads to activation and increased DNA-binding activity of NF-kappaB and induction of iNOS messenger RNA (mRNA) in the absence of cytokines, but not to translation into iNOS protein. Cytokine challenge at low L: -arginine also enhances iNOS mRNA expression, but translation into iNOS protein is diminished, leading to lowered nitric oxide production. The decrease in iNOS protein expression is mediated by the phosphorylation of the translation initiation factor eIF2alpha subunit, a key regulator of cellular translation. In contrast, the mRNA expression of the NF-kappaB-dependent genes IL-1alpha and cationic amino acid transporter-2 (CAT-2) are not affected by the availability of L-arginine. These results demonstrate that the availability of L: -arginine can play a role in the control of gene expression by augmenting the DNA-binding activity of NF-kappaB, which can affect the initiation and progression of dermal inflammation. PMID- 17340134 TI - Hemophagocytic syndrome in a pregnant patient with systemic lupus erythematosus, complicated with preeclampsia and cerebral hemorrhage. PMID- 17340135 TI - High frequency of primary cutaneous lymphomas associated with lymphoproliferative disorders of different lineage. AB - In patients suffering from primary cutaneous lymphomas, secondary malignancies of various origin may develop. However, the frequency of a second neoplasm deriving from another lymphoid lineage is still unclear and may be underestimated. We screened all our patients with primary cutaneous lymphomas from a 4-year recruitment period for a coexisting secondary lymphoproliferative disorder. The cohort comprised of a total of 82 patients with primary cutaneous lymphomas, 62 with primary cutaneous T-cell lymphoma (CTCL), 18 with primary cutaneous B-cell lymphomas, and two with CD4+/CD56+ hematodermic neoplasm/blastic lymphomas. Seven patients (8.5%) were identified with a coexisting lymphoma of a different lymphoid lineage. Four patients with Sezary syndrome (SS) suffered from systemic B-cell lymphoma. Two of these developed SS after chemotherapy of their B-cell lymphoma. The other three patients with various types of skin lymphomas (SS, Mycosis fungoides [MF], primary cutaneous marginal zone lymphoma) developed Hodgkin's disease (hairy cell leukemia). Our data indicate that patients with primary cutaneous lymphomas have an elevated risk for the development of a secondary lymphoproliferative disorder even without previous chemotherapy. Possible explanations for this association include a genetic predisposition, alterations in early progenitor cells, underlying viral infections, and/or stimulation of a B-cell clone by the malignant helper T cells of the primary CTCL and vice versa. PMID- 17340136 TI - 16189 Mitochondrial variant and iron overload. PMID- 17340137 TI - CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age. AB - Clinical resistance to chemotherapy in acute myeloid leukemia (AML) is associated with the expression of the multidrug resistance (MDR) proteins P-glycoprotein, encoded by the MDR1/ABCB1 gene, multidrug resistant-related protein (MRP/ABCC1), the lung resistance-related protein (LRP), or major vault protein (MVP), and the breast cancer resistance protein (BCRP/ABCG2). The clinical value of MDR1, MRP1, LRP/MVP, and BCRP messenger RNA (mRNA) expression was prospectively studied in 154 newly diagnosed AML patients >or=60 years who were treated in a multicenter, randomized phase 3 trial. Expression of MDR1 and BCRP showed a negative whereas MRP1 and LRP showed a positive correlation with high white blood cell count (respectively, p < 0.05, p < 0.001, p < 0.001 and p < 0.001). Higher BCRP mRNA was associated with secondary AML (p < 0.05). MDR1 and BCRP mRNA were highly significantly associated (p < 0.001), as were MRP1 and LRP mRNA (p < 0.001) expression. Univariate regression analyses revealed that CD34 expression, increasing MDR1 mRNA as well as MDR1/BCRP coexpression, were associated with a lower complete response (CR) rate and with worse event-free survival and overall survival. When adjusted for other prognostic actors, only CD34-related MDR1/BCRP coexpression remained significantly associated with a lower CR rate (p = 0.03), thereby identifying a clinically resistant subgroup of elderly AML patients. PMID- 17340138 TI - Endoscopic calcaneoplasty (ECP) as a surgical treatment of Haglund's syndrome. AB - Posterior calcaneal exostosis treatment modalities showed many controversial opinions. After failure of the conservative treatment, surgical bursectomy and resection of the calcaneal exostosis are indicated by many authors. But clinical studies also show a high rate of unsatisfactory results with a relative high incidence of complications. The minimal surgical invasive technique by an endoscopic calcaneoplasty (ECP) could be an option to overcome some of these problems. We operated on 81 patients with an age range between 25 and 55 years, 40 males and 41 females. The radiologic examination prior to surgery documented in all cases a posterior superior calcaneal exostosis that showed friction to the Achilles tendon. All patients included in the study had neither clinical varus of the hind foot nor cavus deformities. All patients had undergone a trial of conservative treatment for at least 6 months and did not show a positive response. The average follow-up was 35.3 months (12-72). According to the Ogilvie Harris-Score, 34 patients presented good and 41 patients excellent results, while three patients showed fair results, and three patients only poor results. All the post-operative radiographs showed sufficient resection of the calcaneal spur. Only minor postoperative complications were observed. ECP is an effective and of minimal-invasive procedure for the treatment of patients with calcaneal exostosis. After a short learning curve, the endoscopic exposure is superior to the open technique has less morbidity, less operating time, and nearly no complications; moreover, the pathology can better be differentiated. PMID- 17340139 TI - Global models from the Canadian lynx cycles as a direct evidence for chaos in real ecosystems. AB - Real food chains are very rarely investigated since long data sequences are required. Typically, if we consider that an ecosystem evolves with a period corresponding to the time for maturation, possessing few dozen of cycles would require to count species over few centuries. One well known example of a long data set is the number of Canadian lynx furs caught by the Hudson Bay company between 1821 and 1935 as reported by Elton and Nicholson in 1942. In spite of the relative quality of the data set (10 undersampled cycles), two low-dimensional global models that settle to chaotic attractors were obtained. They are compared with an ad hoc 3D model which was proposed as a possible model for this data set. The two global models, which were estimated with no prior knowledge about the dynamics, can be considered as direct evidences of chaos in real ecosystems. PMID- 17340140 TI - Assessing diversity of arbuscular mycorrhizal fungi in a local community: role of sampling effort and spatial heterogeneity. AB - Diversity of arbuscular mycorrhizal fungi (AMF) was assessed in two 9.2 x 9.2-m plots planted with landscape trees and shrubs at an experimental site in Phoenix, AZ, USA. Twenty-five soil samples were collected in a regular grid pattern from each plot, and AMF species were identified using trap cultures. A total of 12 species were detected, with 7 species detected in one plot and 11 in the other. We found that sampling effort had a major impact on assessing species richness and composition in this local community. Fifteen samples would be necessary to detect 70-80% of species present in each plot. A limited number of additional undetected species are likely to be present in both plots, based on the sampling effort curves and jackknife estimates. Only two species, Glomus eburneum and Glomus microaggregatum, were detected in over 50% of the samples from both plots, and rank-frequency plots revealed a lognormal species distribution. Despite the patchiness of plants in the plots, the number of species detected per point exhibited spatial structuring only at the smallest sampling scale in a single plot, and only a single species in each plot was not randomly distributed. These results indicate that sampling effort and strategy can affect perceptions of AMF community structure. PMID- 17340141 TI - Community structure of arbuscular mycorrhizal fungi in a primary successional volcanic desert on the southeast slope of Mount Fuji. AB - Community structure of arbuscular mycorrhizal fungi (AMF), evaluated as spore samples and mycorrhizal roots of four herbaceous plant species, was investigated at different altitudes in a primary successional volcanic desert on Mount Fuji using molecular methods (fragment and sequence analysis of the large ribosomal subunit RNA gene). In total, 17 different AMF clades were identified, and most were members of the Glomaceae, Acaulosporaceae, and Gigasporaceae. The AMF community structures detected by spore sampling were inconsistent with those from plant roots. Of all AMF clades, six (35.3%) were detected only on the basis of spores, six (35.3%) only in roots, and five corresponded to both spores and roots (29.4%). Although an Acaulospora species was the most dominant among spores (67.1%), it accounted for only 6.8% in root samples. A species analysis of AMF communities at different altitudes demonstrated that AMF species diversity increased as altitude decreased and that the species enrichment at lower altitudes resulted from the addition of new species rather than species replacement. The inconsistencies in the species composition of spore communities with those in roots and the change in species diversity with altitude are discussed. PMID- 17340142 TI - Habitats of Bulinus truncatus and Planorbarius metidjensis, the intermediate hosts of urinary schistosomosis, under a semiarid or an arid climate. AB - Since Bulinus truncatus and Planorbarius metidjensis are the intermediate hosts of Schistosoma haematobium in southwestern Morocco, five rivers were investigated to identify sites colonized by either of both species and determine the characteristics of their habitats via the study of 12 physicochemical parameters in running water. P. metidjensis was observed in the upper valleys of three rivers, whereas B. truncatus was found in sites of lower altitude. A component analysis demonstrated that altitude (from 4 to 1,380 m), water pH (from 5.9 to 9.2), and electric conductivity (from 120 to 6,020 microS/cm) were the main descriptors of environment. A multiple correspondence analysis showed that P. metidjensis was associated to Ancylus fluviatilis, high altitude, and possibly low electric conductivity. B. truncatus was associated to Melanoides tuberculata and was found in lower altitude sites with medium electric conductivity in water. Using logistic regressions, the main characteristics were altitude and dissolved oxygen for B. truncatus, and chlorides and CaCO3 for P. metidjensis. As the habitats of both S. haematobium intermediate hosts differed from each other by altitude and the frequency of snails, which cohabited with them, these findings may be used to detect the presence of either of both intermediate hosts in numerous spring heads which are present on the western slope of the Anti Atlas mountains and the corresponding valleys. PMID- 17340143 TI - Nitric oxide production and nitric oxide synthase immunoreactivity in Naegleria fowleri. AB - Free-living ameba Naegleria fowleri produces an acute and fatal infectious disease called primary amebic meningoencephalitis (PAM), whose pathophysiological mechanism is largely unknown. The aim of this study was to investigate the role of nitric oxide (NO) in PAM. Although NO has a cytotoxic effect on various parasites, it is produced by others as part of the pathology, as is the case with Entamoeba histolytica. To test for the production of NO, we analyzed whether antibodies against mammalian NO synthase isoforms (neuronal, inducible, and endothelial) presented immunoreactivity to N. fowleri proteins. We found that the trophozoites produced NO in vitro. The Western blot results, which showed N. fowleri trophozoites, contained proteins that share epitopes with the three described mammalian NOS, but have relative molecular weights different than those described in the literature, suggesting that N. fowleri may contain undescribed NOS isoforms. Moreover, we found that trophozoites reacted to the NOS2 antibody, in amebic cultures as well as in the mouse brain infected with N. fowleri, suggesting that nitric oxide may participate in the pathogenesis of PAM. Further research aimed at determining whether N. fowleri contains active novel NOS isoforms could lead to the design of new therapies against this parasite. PMID- 17340144 TI - Modeling the septation initiation network (SIN) in fission yeast cells. AB - Cytokinesis in fission yeast is controlled by a signal transduction pathway called the Septation Initiation Network (SIN). From a dynamical point of view the most interesting questions about the regulation of fission yeast cytokinesis are: how do wild type cells ensure that septation is initiated only once per cycle? Why does the control system stay in a continuously septating state in some mutant strains? And how is it that the SIN remains active when cytokinesis fails? To answer these questions we construct a simplified mathematical model of the SIN and graft this regulatory module onto our previous model of cyclin-dependent kinase (Cdk) dynamics in fission yeast cells. The SIN is both activated and inhibited by mitotic Cdk/cyclin complexes. As a consequence of this dual regulation, the SIN gets activated only once at the end of mitosis, when Cdk activity drops. The mathematical model describes the timing of septation not only in wild type cells but also in mutants where components of the SIN are knocked out. The model predicts phenotypes of some uncharacterized mutant cells and shows how a cytokinesis checkpoint can stop the cell cycle if septation fails. PMID- 17340145 TI - Identification of salt stress inducible genes that control cell envelope related functions in Azospirillum brasilense Sp7. AB - Plant growth promoting rhizobacteria such as Azospirillum brasilense are agronomically important as they are frequently used for crop inoculation. But adverse factors such as increasing soil salinity limit their survival, multiplication and phytostimulatory effect. In order to understand the role of the genes involved in the adaptation of A. brasilense Sp7 to salt stress, a mutant library (6,800 mutants) was constructed after random integration of a mini Transposon Tn5 derivative containing a promoterless gusA and oriV. The library was screened for salt stress inducible Gus activity on minimal malate agar medium containing NaCl and 5-bromo-4-chloro-3-indolyl-beta-D: -glucuronide. Salt stress responsiveness of the promoters was estimated by quantifying GusA activity in the presence and absence of NaCl stress using p-nitrophenyl-beta-D: -glucuronide as a substrate. In 11 mutants showing high levels of gusA expression in the presence of salt-stress, the partial nucleotide sequence of the DNA region flanking the site of Tn5 insertion was determined and analysed using the NCBI-BLAST programs. Similarity searches revealed that 10 out of the 11 genes sequenced showed notable similarity with genes involved in functions related to modulation in the composition of exopolysaccharides, capsular polysaccharides, lipopolysaccharides, peptidoglycan and lipid bilayer of the cell envelope. Induction of cell envelope related genes in response to salt stress and salt sensitive phenotype of several mutants in A. brasilense indicate a prominent role of cell envelope in salt stress adaptation. PMID- 17340146 TI - The role of angiotensin II type 1 receptor-activating antibodies in renal allograft vascular rejection. AB - Acute rejection with vascular involvement remains a challenging problem in renal allotransplantation. Fibrinoid necrosis of the arteries with secondary thrombotic occlusions is C4d negative in 50% of cases and has the worst prognosis among all allograft vascular lesions. Nonhuman leukocyte antigen (HLA) non-complement fixing antibodies reacting to artery-specific antigens have been speculated to be responsible for causing severe vascular injury. We recently reported the presence of agonistic antibodies against the angiotensin II type 1 receptor (AT(1)R-AA) in 16 recipients of renal allografts who had severe vascular rejection and malignant hypertension but who did not have anti-HLA antibodies. AT(1)R-AA stimulate AT(1)R and induce mediators of inflammation and thrombosis. Removal of AT(1)R-AA by plasmapheresis in combination with pharmacologic AT(1)R blockade leads to improved renal function and graft survival in AT(1)R-AA-positive patients. We have shown that the analysis of the subtle diagnostic and mechanistic differences may help to identify patients at particular risk and improve outcome of rejections with vascular pathology. PMID- 17340147 TI - Traditional and "new" cardiovascular risk markers and factors in pediatric dialysis patients. AB - Cardiovascular disease (CVD) is the principal cause of mortality in patients with end-stage renal disease (ESRD). The aim of this study was to analyze carotid intima-media thickness (cIMT), endothelium-dependent dilatation (EDD), and left ventricular mass index (LVMI) as the cardiovascular risk markers and to investigate the independent risk factors of these markers in pediatric dialysis patients. This study included 39 children and adolescents undergoing dialysis (15 hemodialysis and 24 peritoneal dialysis) and 15 age- and gender-matched healthy subjects. The cIMT and EDD were assessed by high-resolution ultrasound, and LVMI was calculated from standard echocardiographic measurements. Compared with control subjects, cIMT standard deviation scores (SDS), LVMI, total homocysteine (tHcy), and high-sensitivity C-reactive protein (hs-CRP) values were significantly higher in patients, but EDD values did not differ. The mean hs-CRP level was significantly higher in hemodialysis (HD) patients than in peritoneal dialysis (PD) patients. The cIMT-SDS and LVMI were associated with several variables in univariate analysis. Stepwise linear regression analysis, indexed SBP (p = 0.017), and hemoglobin (p = 0.001) turned out to be independent variables for predicting LVMI, and a significant predictor of cIMT was indexed diastolic blood pressure (DBP) (p = 0.035). The causes of atherosclerosis and left ventricular hypertrophy are multifactorial in children and adolescents with ESRD. Better management of hypertension and anemia may be priorities for preventing or improving CVD in these patients. PMID- 17340148 TI - The malnutrition and inflammation axis in pediatric patients with chronic kidney disease. AB - Malnutrition and inflammation are closely linked in adult chronic kidney disease (CKD) patients and are both related to poor outcome, but data on pediatric patients are lacking. To describe the prevalence of inflammation, evaluate nutritional status, their correlation to each other, and their possible determinants in pediatric patients with CKD in predialysis, on hemodialysis (HD), and peritoneal dialysis (PD) who were submitted to demographic, nutritional, and inflammatory evaluations. Patients' nutritional status was evaluated according to anthropometric parameters and body composition assessed by measurements of skinfold thickness and bioelectrical impedance. Inflammation was assessed by measurement of highly sensitive C-reactive protein (CRP), ferritin, and albumin. Patients with CRP > 1 mg/l were considered inflamed. Sixty-four pediatric patients (mean age 9 +/- 4 years-, 40% on HD, 22% on PD, and 38% predialysis) were studied. Mean CRP concentration was 3.4 +/- 6.5 mg/l (median 0.78 mg/l, range 0.78-33.4 mg/l), and 41% presented CRP levels above 1 mg/l. Mean ferritin was 148 +/- 197 mg/dl and was above the normal reference values in 28% of patients. On the other hand, mean albumin was 3.9 +/- 0.5 mg/dl, below reference value in only 13% of patients. A larger proportion of HD patients (52%) were inflamed compared with those on PD (31%; p < 0.05). Malnutrition prevalence varied from 5% to 65% according to the method used. While inflamed patients presented lower serum bicarbonate and were on HD for a longer time, there were no consistent associations between malnutrition and inflammation. Inflammation is highly prevalent in the pediatric CKD population and was not consistently related to malnutrition. Other risk factors linked to high mortality and morbidity (acidosis and longer time on dialysis) were associated with inflammation. Prospective studies will need to analyze the predictive value of inflammation and malnutrition markers in the pediatric CKD population. PMID- 17340149 TI - The human genome-wide distribution of DNA palindromes. AB - In this work, we performed a systematic study of perfect and nonspacer palindromes present in human genomic DNA, and we investigated palindrome distribution over the entire human genome and over the functional regions such as the exon, intron, intergenic, and upstream regions (2,000 bp upstream from translational start site). We found that 24 palindrome-abundant intervals are mostly located on G-bands, which condense early, replicate late, and are relatively A+T rich. In general, palindromes are overrepresented in introns but underrepresented in exons. Upstream region has enriched palindrome distribution, where palindromes can serve as transcription factor binding sites. We created a Human DNA Palindrome Database (HPALDB) which is accessible at http://vhp.ntu.edu.sg/hpaldb . It contains 12,556,994 entries covering all palindromes in the human genome longer than 6 bp. Queries can be performed in different ways. Each entry in the database is linked to its location on NCBI's human chromosome Map Viewer. PMID- 17340150 TI - The ring nerve of the box jellyfish Tripedalia cystophora. AB - Box jellyfish have the most elaborate sensory system and behavioural repertoire of all cnidarians. Sensory input largely comes from 24 eyes situated on four club shaped sensory structures, the rhopalia, and behaviour includes obstacle avoidance, light shaft attractance and mating. To process the sensory input and convert it into the appropriate behaviour, the box jellyfish have a central nervous system (CNS) but this is still poorly understood. The CNS has two major components: the rhopalial nervous system and the ring nerve. The rhopalial nervous system is situated within the rhopalia in close connection with the eyes, whereas the ring nerve encircles the bell. We describe the morphology of the ring nerve of the box jellyfish Tripedalia cystophora as ascertained by normal histological techniques, immunohistochemistry and transmission electron microscopy. By light microscopy, we have estimated the number of cells in the ring nerve by counting their nuclei. In cross sections at the ultrastructural level, the ring nerve appears to have three types of neurites: (1) small "normal" looking neurites, (2) medium-sized neurites almost completely filled by electron lucent vacuoles and (3) giant neurites. In general, only one giant neurite is seen on each section; this type displays the most synapses. Epithelial cells divide the ring nerve into compartments, each having a tendency to contain neurites of similar morphology. The number and arrangement of the compartments vary along the length of the ring nerve. PMID- 17340151 TI - Intra-epithelial spicules in a homosclerophorid sponge. AB - Attempts to understand the intricacies of biosilicification in sponges are hampered by difficulties in isolating and culturing their sclerocytes, which are specialized cells that wander at low density within the sponge body, and which are considered as being solely responsible for the secretion of siliceous skeletal structures (spicules). By investigating the homosclerophorid Corticium candelabrum, traditionally included in the class Demospongiae, we show that two abundant cell types of the epithelia (pinacocytes), in addition to sclerocytes, contain spicules intracellularly. The small size of these intracellular spicules, together with the ultrastructure of their silica layers, indicates that their silicification is unfinished and supports the idea that they are produced "in situ" by the epithelial cells rather than being incorporated from the intercellular mesohyl. The origin of small spicules that also occur (though rarely) within the nucleus of sclerocytes and the cytoplasm of choanocytes is more uncertain. Not only the location, but also the structure of spicules are unconventional in this sponge. Cross-sectioned spicules show a subcircular axial filament externally enveloped by a silica layer, followed by two concentric extra axial organic layers, each being in turn surrounded by a silica ring. We interpret this structural pattern as the result of a distinctive three-step process, consisting of an initial (axial) silicification wave around the axial filament and two subsequent (extra-axial) silicification waves. These findings indicate that the cellular mechanisms of spicule production vary across sponges and reveal the need for a careful re-examination of the hitherto monophyletic state attributed to biosilicification within the phylum Porifera. PMID- 17340152 TI - Elevated expression of genes assigned to NF-kappaB and apoptotic pathways in human periodontal ligament fibroblasts following mechanical stretch. AB - There is growing evidence that apoptosis involves the nuclear transcription factor NF-kappaB in conjunction with related genes. However, in the context of mechanical orthodontic forces, force-sensing target genes assigned to pathways of NF-kappaB and apoptosis have not been fully characterised. To contribute to the identification of putative target genes, we used cDNA arrays specific for NF kappaB and apoptotic pathways and analysed elevated gene expression in primary human periodontal ligament fibroblasts (PDL-F) after a 6 h application of mechanical force. Among several identified genes (including several caspases), interleukin-1 beta (IL-1 beta) and NF-kappaB displayed significantly higher expression on the NF-kappaB array, whereas higher expression was obtained for BCL2-antagonist of cell death (BAD), member 6 of the TNF-receptor superfamily (FAS) and CASP2 and RIPK1 domain-containing adaptor with death domain (CRADD) on the apoptosis array. Based on a defined cut-off level of a more than 1.5-fold higher expression, this significance in elevated gene expression was corroborated by reverse transcription/polymerase chain reaction (RT-PCR). Here, semi quantitative (sq) PCR revealed a more pronounced elevation of mRNA gene expression in PDL-F after 6 h of stretch, when compared with 12 h. Moreover, the elevation after 6 h as observed by sq-PCR was convergent with quantitative PCR (q PCR). q-PCR yielded levels of 5.8-fold higher relative gene expression for IL-1 beta and 1.7-fold for NF-kappaB, whereas that computed for BAD indicated a 5.2 fold, for CRADD a 2.1-fold and for FAS a 2.0-fold higher expression. The data obtained from the expression analysis thus indicate a stretch-induced transcriptional elevation of genes assigned to the NF-kappaB and apoptotic pathways. This elevation may render them target candidates for being addressed by mechanical orthodontic forces. PMID- 17340153 TI - Achieving the ideal properties for vascular bypass grafts using a tissue engineered approach: a review. AB - The multiple demands placed on small calibre cardiovascular bypass grafts have meant that a synthetic prosthesis with good long-term patency has not been developed. A tissue-engineered graft could fulfil the ideal characteristics present in an artery. However, the great disadvantage of such a conduit is the time necessary for maturation leading to unacceptable delays once the decision to intervene surgically has been made. This maturation process is essential to produce a graft which can withstand haemodynamic stress. Once implanted, the tissue-engineered graft can contract in response to immediate haemodynamic conditions and remodel in the long term. We review the latest tissue engineering approaches used to give the favourable properties of mechanical strength, arterial compliance, low thrombogenicity, long-term resistance towards biodegradation as well as technological advances which shorten the time required for production of an implantable graft. PMID- 17340154 TI - Bone strains around apically free versus grafted implants in the posterior maxilla of human cadavers. AB - The objective of this study was to compare the bone strains of apically free versus grafted implants in the posterior maxilla. The experiments were undertaken in four edentulous maxillary posterior regions of fresh human cadavers, having a minimum bone height of 8 mm. In each bone fragment, two O 4.1 mm x 12 mm Straumann implants were placed, and insertion torque values (ITV) and implant stability quotients (ISQ) of the implants were quantified to determine implant anchorage. Two splinted crowns were fabricated for each experimental model. Strain gauges were bonded on the buccal and sinus floor cortical bones around apically free and grafted implants. Microstrains were recorded by a data acquisition system and corresponding software at a sample rate of 10 KHz under central and buccally oriented lateral-axial static loads of 100 and 150 N in separate cases. The data were compared by independent T test at a significance level set at P<0.05. Bone tissue strains on the buccal cortical areas adjacent to apically free implants were higher than those of apically grafted implants (P<0.05). The differences ranged between 10 and 48 mu epsilon under central and lateral axial loads of 100 and 150 N. The shift in load application from central to buccally oriented lateral axial mode increased strains between 60 and 201 mu epsilon on buccal cortical bone around apically free and grafted implants (P<0.05). Bone strains around anterior implants were higher than those of posterior implants. Microstrains in the sinus floor cortical bone in apically grafted models were slightly higher than apically free models. Bone tissue strains on the buccal cortical areas adjacent to apicallyfree implants are higher than those of apically grafted implants. Sinus lifting, resulting in an enhanced apical support, slightly increases strains at the sinus floor region, but leads to a decrease in bone strains around the collar of supporting implants. PMID- 17340155 TI - Laser Doppler perfusion monitoring and imaging: novel approaches. AB - Laser Doppler flowmetry (LDF) is a non invasive method enabling the monitoring of microvascular blood flow, a very important marker of tissue health. This article gives an overview on the concept of LDF for microvascular perfusion monitoring and imaging. It first describes the theoretical background of the technique. Then, the benefits of LDF signal processing are shown through clinical examples: use of time-frequency representations and wavelets. Afterwards, the paper introduces novel approaches of velocity components. For that purpose, a work providing the determination of the velocities relative contribution in physiologically relevant units (mm/s) is presented. Imaging perfusion is also reviewed through methods based on laser speckle. The most prominent disadvantage of the latter devices being the time needed to produce a perfusion image, solutions are proposed in the last part of the paper. PMID- 17340156 TI - The effects of load carriage and bracing on the balance of schoolgirls with adolescent idiopathic scoliosis. AB - The balance function of children is known to be affected by carriage of a school backpack. Children with adolescent idiopathic scoliosis (AIS) tend to show poorer balance performance, and are typically treated by bracing, which further affects balance. The objective of this study is to examine the combined effects of school backpack carriage and bracing on girls with AIS. A force platform was used to record center of pressure (COP) motion in 20 schoolgirls undergoing thoraco lumbar-sacral orthosis (TLSO brace) treatment for AIS. COP data were recorded with and without brace while carrying a backpack loaded at 0, 7.5, 10, 12.5 and 15% of the participant's bodyweight (BW). Ten participants stood on a solid base and ten stood on a foam base, while all participants kept their eyes closed throughout. Sway parameters were analyzed by repeated measures ANOVA. No effect of bracing was found for the participants standing on the solid base, but wearing the brace significantly increased the sway area, displacement and medio-lateral amplitude in the participants standing on the foam base. The medio-lateral sway amplitude of participants standing on the solid base significantly increased with backpack load, whereas significant increases in antero-posterior sway amplitude, sway path length, sway area per second and short term diffusion coefficient were found in participants standing on the foam base. The poorer balance performance exhibited by participants with AIS when visual and somatosensory input is challenged appears to be exacerbated by wearing a TLSO brace, but no interactive effect between bracing and backpack loading was found. PMID- 17340157 TI - Holmium laser for stone management. AB - The efficiency and safety profile of the holmium laser has made this tool a versatile multi-purpose instrument for use in the endoscopic treatment of a wide variety of urologic disorders, in particular urinary calculi. Herein we review holmium laser physics, current endourologic laser lithotripsy applications, and the performance of new low power holmium laser devices. PMID- 17340158 TI - Targeting vascular endothelial growth factor (VEGF)-receptor-signaling in renal cell carcinoma. AB - Metastatic renal cell carcinoma (RCC) is resistant to conventional chemotherapy. Combined data for a variety of immunotherapies resulted in an overall chance of partial (PR) or complete remission (CR) of only 12.9%. There is a clear need for novel, more effective therapies to prevent relapse, control metastases and improve overall survival. Improved understanding of RCC disease biology has led to the introduction of molecularly targeted treatment strategies in these cancers. Von Hippel-Lindau (VHL) gene inactivation is observed in most clear cell renal carcinoma, resulting in vascular endothelial growth factor (VEGF) over expression and driving the malignant phenotype. This review discusses the efficacy of novel therapies targeting the VEGF receptor (VEGFR) (e.g. anti-VEGF antibodies, VEGFR tyrosine kinase inhibitors, mTOR inhibitors), some of which were recently approved by the Food and Drug Administration/European Medicines Evaluation Agency (FDA/EMEA) and represent the new treatment standards in RCC patients. PMID- 17340159 TI - Management of erectile dysfunction after radical prostatectomy in 2007. AB - As radical prostatectomy (RP) remains a commonly used procedure in the treatment of clinically localized prostate cancer, we critically analyzed the evidence suggesting the role of pharmacological prophylaxis and treatment of erectile dysfunction (ED) after surgery. Systematic literature review using Medline and Cancerlit from January 1997 to December 2006. Abstracts published in the journals European Urology, The Journal of Urology, The International Journal of Impotence Research and The Journal of Sexual Medicine as official proceedings of internationally known scientific Societies held in the same time period were also assessed. Patient selection and surgical technique (i.e., preservation of neurovascular bundles) are the major determinants of post-operative erectile function. Pharmacological treatment of post-operative ED, using either oral or local approaches, is effective and safe. Moreover, recent studies have shown that pharmacological prophylaxis early after RP can significantly improve the rate of erectile function recovery after surgery. Use of on-demand treatments for treatment of ED in patients subjected to RP has been shown to be highly effective, especially in case of properly selected young patients treated with a bilateral nerve-sparing approach by experienced surgeons. In this context, pharmacological prophylaxis may potentially have a significant expanding role in future strategies aimed at preserving post-operative erectile function. PMID- 17340160 TI - Does noncomplicated acute appendicitis cause bacterial translocation? AB - It is unknown whether noncomplicated acute appendicitis cause bacterial translocation. In this study, we aimed to test development of the bacterial translocation in the patients who were operated for acute appendicitis. In this prospective study, 10 control patients who underwent elective operations because of other reasons, and 18 patients with noncomplicated acute appendicitis were evaluated. No patients took prophylactic antibiotic. After laparotomy, samples were obtained from peritoneal leaf just close to wound edge, and peritoneal swab culture from right paracolic region. Before appendectomy, a mesenteric lymph node (MLN) adjacent to the terminal ileum was taken out. Tissue samples were placed in a sterile container for microbiological analysis, and 10% formalin for histopathological analysis. Control samples had no bacterial translocation. Only 3 of 18 (16.6%) patients with appendicitis included bacterial translocation to MLN. There was no significant difference between both groups. No bacterial colonization was detected in the peritoneal tissue and peritoneal swab culture. Peritoneal tissue injury score was 2 +/- 1.4 in controls and 2.8 +/- 1.7 in the patients with appendicitis (P>0.05). MLN injury score was 2.5 +/- 1.3 in controls and 3.2 +/- 1.5 in the patients with appendicitis (P>0.05). No patient developed wound and systemic infection. No significant bacterial translocation frequency and tissue injury score was identified in the children with noncomplicated acute appendicitis. This result suggests that antibiotic prophylaxis may be unnecessary in such patients. PMID- 17340161 TI - Shoulder MR arthrography of the posterior labrocapsular complex in overhead throwers with pathologic internal impingement and internal rotation deficit. AB - PURPOSE: To determine if overhead-throwing athletes with internal impingement pain and internal rotation deficit have thickening of the posterior inferior labrocapsular complex on MR arthrogram images. MATERIALS AND METHODS: This study was approved and a waiver of consent granted by our institutional review board. Twenty-six overhead-throwing athletes with internal impingement pain and internal rotation deficit, and 26 controls who had undergone MR arthrograms, were retrospectively examined. The MR studies were combined and read in a blind fashion. On an axial image through the posteroinferior glenoid rim, the readers measured the labral length, capsule-labrum length, and the posterior recess angle. A t-test was used to determine statistical significance. RESULTS: The mean labral length was 4.9 mm [standard deviation (SD) 1.4 mm] for the controls, and 6.4 mm (SD 1.6 mm) for the athletes (P = 0.001). The mean capsule-labrum length was 5.4 mm (SD 2.1 mm) for the controls, and 8.8 mm (SD 2.9 mm) for the athletes (P < 0.001). The mean posterior recess angle measured 65 degrees (SD 27 degrees) for the controls and 94 degrees (SD 38 degrees) for the athletes (P = 0.002). CONCLUSIONS: Overhead-throwing athletes with internal impingement pain and internal rotation deficit tend to have a thicker labrum and a shallower capsular recess in the posterior inferior shoulder joint than do non-overhead-throwing athletes. In many, the posteroinferior capsule is also thickened. These MR findings should alert the radiologist to closely inspect the posterior cuff and posterosuperior labrum for the tears associated with internal impingement. PMID- 17340162 TI - MRI findings of prolonged post-traumatic sternal pain. AB - OBJECTIVE: The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. DESIGN AND PATIENTS: Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. RESULTS: Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. CONCLUSION: Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma related abnormalities of the sternum following chest trauma. PMID- 17340163 TI - SLAP lesion: what is it...really? PMID- 17340164 TI - The "penumbra sign" on T1-weighted MRI for differentiating musculoskeletal infection from tumour. AB - OBJECTIVE: The "penumbra sign" on unenhanced T1-weighted MR sequences is thought to be helpful for discriminating subacute osteomyelitis from bone neoplasm. We sought to quantify the sensitivity and specificity of this sign for bone and soft tissue infection in a general referral population. DESIGN: Clinical coding was used to identify patients admitted to Middlemore Hospital (Auckland, New Zealand) between January 2000 and November 2003 with a diagnosis of either infection or neoplasm of the upper or lower limb who had undergone an MRI scan. One hundred and eighty-three patients were included in the study. Fifty-seven patients had bone or soft tissue infection. One hundred and twenty-six had a bone or soft tissue neoplasm. Relevant unenhanced T1-weighted images were selected for each patient, randomised and placed in a folder on the Hospital PACS system. Four reviewers were shown the original article describing the penumbra sign and then asked to look at the images in the folder stating whether the penumbra sign was present or absent. RESULTS: The average specificity and sensitivity of the penumbra sign for musculoskeletal infection was 96% (range 94-99%) and 27% (range 21-34%) respectively. Interobserver reliability was moderate to good with an average kappa score of 0.57 (range 0.50-0.62). For isolated soft tissue infection there was a higher sensitivity (54%, 33-83%) but with similar specificity (98%, 96-100%) and interobserver reliability (0.47, 0.33-0.58). Of the 11 out of 57 (19%) true positive penumbra signs identified by a consensus of three or more of the observers, all were subacute, chronic or acute on chronic infections. CONCLUSIONS: The penumbra sign has a high specificity for musculoskeletal infection. This is also true for isolated soft tissue infection. The penumbra sign is helpful in differentiating neoplasm from infection and its presence in the setting of a high pretest probability is useful in making a diagnosis of infection. PMID- 17340165 TI - Bisphosphonates. PMID- 17340166 TI - Cervical interlaminar epidural steroid injection for neck pain and cervical radiculopathy: effect and prognostic factors. AB - OBJECTIVE: To verify the usefulness of a fluoroscopy guided cervical interlaminar epidural steroid injection (CIESI) in patients with neck pain and cervical radiculopathy and to evaluate outcome predictors. DESIGN: We retrospectively analyzed 91 patients from July 2004 to June 2005 in whom CIESI was initially performed for neck pain and cervical radiculopathy. Therapeutic effects were evaluated 2 weeks after the administration of CIESI, and CIESI effectiveness was graded using a five-point scale, namely, whether the pain had disappeared, was much improved, slightly improved, the same, or aggravated. We also used a visual analog scale (VAS) for the clinical evaluation. According to documentation and follow-up charts, we categorized treatments as effective or ineffective. Possible outcome predictors, namely, diagnosis (spinal stenosis vs herniated disc), primary symptoms (neck pain vs radiculopathy vs both), age, gender, and duration of pain (more or less than 6 months) were also analyzed. Fisher's exact test, the chi-square test, and multiple logistic regression analysis were used for the statistical analysis. PATIENTS: After their medical records had been reviewed, 76 patients were included in this study. Inclusion criteria were: the availability of a cross-sectional image, such as a CT scan or an MR image, and a follow-up record after injection. RESULTS AND CONCLUSIONS: The medical records of 76 patients (male:female = 41 : 35) of mean age 53.1 years (range 32 years to 82 years) were reviewed. Two weeks after injection, 55 patients (72.4%) had experienced effective pain relief. Patients with herniated discs had significantly better results than patients with spinal stenosis (86.1% vs 60.0%) (P < 0.05). Other non-significant predictors of an improved outcome included: a symptom duration of <6 months, a young age, and the presence of cervical radiculopathy. Multiple regression analysis showed that the only factor that was significantly associated with outcome was the cause of the pain, i.e., herniated disc or spinal stenosis. Fluoroscopy guided CIESI is a safe and effective means of treating patients with neck pain and cervical radiculopathy. The most important outcome predictor was cause of pain, and patients with herniated disc experienced better pain relief than those with spinal stenosis. PMID- 17340167 TI - Comparison of fixation methods of double-bundle double-tibial tunnel ACL reconstruction and double-bundle single-tunnel technique. AB - An experimental study was conducted in order to evaluate biomechanical methods of single-bundle reconstruction in ACL and compare it with a new double-bundle double-tibial tunnel technique. Twenty-four porcine cadaver knees, divided into 4 groups of 6 knees each and 48 proper extensors of the fourth toe tendons, were used for the fixation techniques. In groups A and B, a double-bundle technique with a single femoral and tibial tunnel was used, fixed to a femoral and tibial post with screws and with buttons, respectively. In groups C and D, a double bundle technique (technique Delta) with two separate tibial tunnels was used, fixed to a femoral and tibial post with screws and with buttons, respectively. A material testing system (Instron) was used for anteriorly translating the tibia until failure. The femoral and tibial post as a fixation method is superior to the conventional buttons technique. The more anatomical double-bundle reconstruction technique provided significantly higher structural properties and smaller loss of fixation compared with the single-bundle reconstruction technique. The comparison of the two techniques gave superior results to the femoral and tibial screws over the buttons. The double-bundle technique attempts to restore the anterior stability of the knee joint. PMID- 17340168 TI - Image-guided percutaneous biopsy of musculoskeletal lesions in children. AB - BACKGROUND: Percutaneous core needle biopsy (PCNB) of musculoskeletal lesions can provide early and definitive diagnosis and guide decisions on management. The technique is less invasive than open biopsy and has a low complication rate. OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy and safety of image-guided PCNB of musculoskeletal lesions in children. MATERIALS AND METHODS: Retrospective review of the medical records of patients referred for PCNB of musculoskeletal lesions was performed. Data collected included tumor type and complication rates. Lesion "hit" or "missed", and core adequacy and ability to reach a definitive pathological diagnosis were reviewed and used to determine whether the biopsy was overall successful or unsuccessful. RESULTS: A total of 127 biopsies were performed in 111 patients. Of the 127 PCNB procedures, 114 "hit" the lesion and 13 "missed," and 120 of the cores provided for analysis were deemed adequate for pathological interpretation and 7 were deemed inadequate. A definitive pathological diagnosis was possible in 97 of the 127 PCNB preocedures and not possible in 30. Overall 76% of the PCNB procedures were successful. The diagnostic success of biopsy in primary malignant tumors was significantly higher (92%) than in primary benign tumors (65%; P=0.008). Six minor complications resulted from PCNB. CONCLUSION: This study showed that PCNB is accurate and safe for the diagnosis of musculoskeletal lesions in pediatric patients, and its results are comparable to those in adult studies. PMID- 17340170 TI - Reaction time of facial affect recognition in Asperger's disorder for cartoon and real, static and moving faces. AB - This study used a choice reaction-time paradigm to test the perceived impairment of facial affect recognition in Asperger's disorder. Twenty teenagers with Asperger's disorder and 20 controls were compared with respect to the latency and accuracy of response to happy or disgusted facial expressions, presented in cartoon or real images and in static or moving conditions. Group analysis revealed that the Asperger group did not differ significantly from the control group in speed and accuracy for both affects and in all presentation modalities. Individual analysis, however, revealed that the proportion of participants exhibiting a happy face advantage was smaller in the Asperger group than in the control group. The results did not support the notion of impairment in facial affect recognition in terms of speed and accuracy in Asperger's disorder. Findings also revealed that the absence of happy face advantage was more prevalent in individuals with Asperger's disorder. PMID- 17340171 TI - The molecular identity and characterization of a Proton-coupled Folate Transporter--PCFT; biological ramifications and impact on the activity of pemetrexed. AB - Membrane transport of folates is essential for the survival of all mammalian cells and transport of antifolates is an important determinant of antifolate activity. While a major focus of attention has been on transport mediated by the reduced folate carrier and folate receptors, a very prominent carrier-mediated folate transport activity has been recognized for decades with a low-pH optimum and substrate specificity distinct from that of the reduced folate carrier which operates most efficiently at neutral pH. This low-pH transporter represents the mechanism by which folates are absorbed in the small intestine and it is also widely expressed in other human tissues and solid tumors. Recently, this laboratory discovered the molecular identity of this transporter which is genetically unrelated to the reduced folate carrier. This transporter is proton coupled, electrogenic, and manifests a substrate specificity that is similar to that of the low-pH transport activity previously described in mammalian cells. The key role this transporter plays in intestinal folate absorption has been confirmed by the demonstration of a mutation in this gene in the rare autosomal recessive disorder, hereditary folate malabsorption. This article reviews (1) the characteristics and prevalence of the low-pH folate transport activity, (2) its relationship to, and properties of, the recently identified Proton-Coupled Folate Transporter (PCFT), (3) the physiological and pharmacological roles of this transporter, particularly with respect to pemetrexed, and (4) the historical controversy, now resolved, on the mechanism of intestinal folate absorption. PMID- 17340173 TI - Socio-demographic differences in acculturation and mental health for a sample of 2nd generation/early immigrant Arab Americans. AB - This study examined socio-demographic differences in acculturation patterns among early immigrant and second-generation Arab Americans, using data from 120 participants who completed a Web-based study. Although sex, age, education, and income did not significantly relate to the acculturation process, respondents who were female and those who were married reported greater Arab ethnic identity and religiosity. Striking differences were found based on religious affiliation. Christian patterns of acculturation and mental health were consistent with acculturation theory. For Muslims, however, integration was not associated with better mental health, and religiosity was predictive of better family functioning and less depression. The results of this study suggest unique acculturation patterns for Christian and Muslim subgroups that can better inform future research and mental health service. PMID- 17340172 TI - Neuroendocrine factors in the initiation of puberty: the emergent role of kisspeptin. AB - Puberty is the end-point of a complex series of developmental events, defined by the dynamic interaction between genetic factors and environmental cues, ultimately leading to the attainment of reproductive capacity. The neuroendocrine basis of puberty has been the subject of extensive investigation in the last decades, and identification of the trigger(s) of puberty onset has drawn considerable attention. In this context, recognition of the fundamental role of kisspeptin (encoded by the KiSS-1 gene) and its receptor GPR54 as major gatekeepers of gonadotropic function in general, and puberty onset in particular, has been a major breakthrough in contemporary Neuroendocrinology. Indeed, during the last 3 years, the so-called KiSS-1/GPR54 system has been substantiated as pivotal regulator of puberty in mammals; the lack of GPR54 signaling being coupled to sexual immaturity (impuberism) in mice and humans. In this review, we will summarize the most salient experimental data (mostly obtained in laboratory animals) demonstrating the key roles of hypothalamic KiSS-1 neurons in the activation of the reproductive axis at puberty, and its regulation by metabolic and, eventually, environmental factors. Whether the KiSS-1 system is the trigger for puberty onset and/or it operates as integrator and effector of up-stream regulatory factors warrants further investigation. PMID- 17340174 TI - Leisure-time physical activity among midlife Korean immigrant women in the US. AB - The purpose of the study was to investigate the level of leisure-time physical activity (LTPA) among midlife Korean American women and to determine the relationships of LTPA with individual characteristics and behavior-specific cognition and affects. A cross-sectional descriptive study of 152 middle-aged Korean American women in Central Texas was conducted using a health-promotion model of physical activity adapted from Pender's Health Promotion Model. The results showed that 32% of the participants were not engaged in any form of exercise. The level of acculturation was not significantly related to the amount of physical activity. After age, level of acculturation, education, income, and marital status were controlled, LTPA was significantly associated with perceived benefits and barriers and social support. Physical inactivity, which was common in this group of immigrant women, warrants further rigorous investigation to determine the dynamics of the women's involvement in more physical activity. PMID- 17340175 TI - Does certificate of need affect cardiac outcomes and costs? AB - Several U.S. states enforce Certificate of Need (CON) regulations, which limit the number of hospitals performing open heart surgery or coronary angioplasty. CON regulations were intended to restrain cost growth and improve quality of care. This study compares mortality rates and costs for cardiac care in states with and without CON. CON appears to raise hospital procedure volume and lower the average cost of care. However, CON is associated with little reduction in inpatient mortality, and it may lead hospitals to operate on more patients than they would otherwise. The claimed welfare benefits of CON regulations require careful reconsideration. PMID- 17340176 TI - Language impairment and sexual assault of girls and women: findings from a community sample. AB - Both children and adults with disabilities face increased prevalence of abuse and assault, including sexual assault. Women and girls are disproportionately the victims of sexual assault in both disabled and nondisabled populations. Communication difficulties have been identified as a factor that may increase the vulnerability of individuals with disabilities to sexual assault. However, few studies have examined whether language impairment increases risk for sexual assault. This study reports on a community sample of children with speech or language impairment, followed to age 25. Sexual assault history was assessed based on two questions from the Composite International Diagnostic Interview Posttraumatic Stress Disorder module. Women with language impairment (n = 33) were more likely than women with unimpaired language (n = 59) to report sexual abuse/assault, controlled for socioeconomic status. Sexual assault was associated with higher rates of psychiatric disorders and poorer functioning. Women with neither language impairment nor a history of sexual assault had fewer psychiatric disorders and higher functioning than women with language impairment and/or a history of sexual assault. PMID- 17340177 TI - Responses to conflict and cooperation in adolescents with anxiety and mood disorders. AB - This study examined patterns of behavioral and emotional responses to conflict and cooperation in adolescents with anxiety/mood disorders and healthy peers. We compared performance on and emotional responses to the Prisoner's Dilemma (PD) game, an economic exchange task involving conflict and cooperation, between adolescents with anxiety/depressive disorders (A/D) (N=21) and healthy comparisons (n = 29). Participants were deceived to believe their co-player (a pre-programmed computer algorithm) was another study participant. A/D adolescents differed significantly from comparisons in patterns of play and emotional response to the game. Specifically, A/D participants responded more cooperatively to cooperative overtures from their co-players; A/D girls also reported more anger toward co-players than did comparison girls. Our findings indicate that A/D adolescents, particularly females, respond distinctively to stressful social interchanges. These findings offer a first step toward elucidating the mechanisms underlying social impairment in youth with internalizing disorders. PMID- 17340178 TI - A meta-analysis of the distinction between reactive and proactive aggression in children and adolescents. AB - The present meta-analytic review aimed to clarify divergent findings concerning the relation between reactive and proactive aggression in children and adolescents. Fifty-one studies with 17,965 participants were included in the analysis. A significant correlation between reactive and proactive aggression was found. The strength of this relation varied considerably between studies, from .10 to .89. Observational assessment and tilt/noise tasks were associated with smaller correlations than questionnaires. Within the large group of questionnaire studies, studies disentangling the form and function of aggression found lower correlations than studies that did not disentangle form and function. Among questionnaire studies, higher reliability was associated with larger correlations. Effect size did not depend on other study characteristics such as sample type, age, and informant type. It is concluded that reactive and proactive aggression are most clearly distinguished with behavioral observations and questionnaires that unravel form and functions of aggression. PMID- 17340179 TI - Rising infant mortality in Delaware: an examination of racial differences in secular trends. AB - OBJECTIVES: Recent increases in the Delaware Infant Mortality Rate (IMR) have been attributed to a rise in the mortality of very low birth weight (VLBW, <1500 g) infants born to mothers of higher socioeconomic status. This study examines whether the determinants of infant mortality trends in Delaware vary by race. METHODS: Linked birth/infant death cohort files for the two periods 1993-1997 and 1998-2002 were used to evaluate the determinants of infant mortality trends separately for White and Black racial groups. Kitagawa analyses determined the components of race-specific infant mortality trends attributable to changes in both the birthweight distribution and birthweight-specific mortality rates. Maternal characteristics were examined to identify factors associated with IMR changes. RESULTS: Between the two time periods, infant mortality increased 23% among White infants and 17% among Black infants. For both races, the infant mortality increase was explained by increases in the incidence and mortality of VLBW infants, specifically below <500 grams for Blacks and <1,000 grams for Whites. The increased incidence of VLBW deliveries was statistically significant only among Whites, almost 40% of which was explained by an increase in multiple births. For both Whites and Blacks, the increase in VLBW mortality occurred mainly among births to more traditionally advantaged women who were twenty or older, at least high school educated, married, privately insured, had received first trimester prenatal care, and those who delivered multiple births. CONCLUSIONS: These findings suggest that conventional strategies of increasing access to prenatal care among disadvantaged women may be insufficient to reverse recent IMR increases in Delaware, irrespective of race. Future efforts should focus on understanding the causes of the increased infant mortality associated with higher socioeconomic status, including changes in assisted reproductive technology utilization, maternal health status, and obstetric practice. PMID- 17340180 TI - Trends in prenatal discussion and HIV testing, 1996-2001: Pregnancy Risk Assessment Monitoring System. AB - OBJECTIVE: To assess trends in prenatal discussions about HIV testing and prenatal HIV testing during the period 1996-2001. METHODS: Using data from the Pregnancy Risk Assessment Monitoring System, a population-based postpartum survey of women, we calculated the self-reported prevalences of discussion of prenatal HIV testing and testing. Data were analyzed using SUDAAN; trends were calculated by logistic regression for states having >/=3 years of data. RESULTS: From 1996 to 2001, significant increases in prenatal discussions about HIV testing were seen in 15 of 17 states. During the period 1996-2001, the prevalence of testing increased significantly in 7 of 8 states. In all states, there was a significant, positive relationship between having a prenatal discussion about testing and having an HIV test (odds ratios ranged from 1.7 to 4.9). CONCLUSIONS: We found statistically significant increases in discussions and testing from 1996 through 2001, consistent with guidelines emphasizing routine prenatal testing. Health care providers may have a strong influence on women's decisions to be tested. Because current guidelines call for simplified strategies to reduce barriers to universal prenatal HIV screening, trends in prenatal HIV testing should continue to be monitored to assess the impact of these changes. PMID- 17340181 TI - Using state lead poisoning surveillance system data to assess false positive results of capillary testing. AB - OBJECTIVE: The purpose of this study was to determine the false positive percentage of capillary blood lead screening in a statewide surveillance system and to explore potential predictors of false positive results. METHODS: Data were all blood lead tests of 0-5 year old children in Maine during 2002-2003. We determined the proportion of children with elevated (>/=10 microg/dL) capillary test results who received a venous confirmatory test, and calculated the percentage of false positive tests, defined as a capillary test of >/=10 microg/dL with a confirmatory venous test of <10 microg/dL. Multivariable binomial regression was used to determine whether capillary blood lead level and length of time between capillary and venous tests predicted false positive results, after controlling for potential confounders. We also examined the positive bias of the capillary test among both false positive and true positive results. RESULTS: Seventy-three percent of elevated capillary screening tests (2.2 percent of all capillary screening tests) were false positives. False positive results were less likely for capillary levels of 15-19 microg/dL (RR=0.78; 95% CI 0.5-0.92) and 20 microg/dL or above (RR=0.83; 95% CI 0.71-0.96) compared to 10-14 microg/dL. The percentage of false positives did not vary by interval between screening and confirmatory tests. The capillary test exhibited a positive bias compared to the venous test, even among true positive results. CONCLUSIONS: False positive results may have been caused by sample contamination, rather than laboratory error or true variation in blood lead level between screening and confirmatory tests. Capillary screening could be improved by training in proper sample collection methods. PMID- 17340182 TI - Seat belt use, counseling and motor-vehicle injury during pregnancy: results from a multi-state population-based survey. AB - OBJECTIVES: Motor-vehicle injuries are the leading cause of death and hospitalized trauma during pregnancy. The study objectives were to report the prevalence of seat belt counseling by prenatal care providers during pregnancy, seat belt use during the last trimester, and self-reported motor-vehicle injury during pregnancy. Differences were examined by age, race and education. METHODS: A cross-sectional study design using self-reported 22 state data from the Centers for Disease Control and Prevention's 2001 Pregnancy Risk Assessment Monitoring System (PRAMS) were used (n = 37,081). Estimates were computed using logistic regression from weighted counts. RESULTS: On average, reported prenatal care provider counseling for seat belt use occurred in 48.7% (38.2-58.8%) of prenatal visits. Women most likely to report being counseled were aged 20-29, non-White, Hispanic ethnicity, and less educated. Women 30 years of age or greater and that had a greater than high school education were more likely to report always wearing seat belts in the last trimester. On average, 2.3% (1.2-4.7%) of respondents reported being hurt in a "car accident" during pregnancy. Women less than 20 years old (3.0%), Black (3.9%), and less educated (3.2%) were the most likely to report being hurt in a crash during pregnancy. CONCLUSIONS: Based on PRAMS, it is estimated that about 92,500 pregnant women are hurt annually in motor-vehicle crashes in the United States. Despite this reported risk and the proven efficacy of restraint use, most pregnant women do not report being counseled about seat belt use during prenatal visits. Limitations of PRAMS methodology make it difficult to determine the association of prenatal counseling with seat belt use. PMID- 17340183 TI - Linking mental health and after school systems for children in urban poverty: preventing problems, promoting possibilities. AB - The current mental health system is failing to meet the extensive needs of children living in urban poverty. After school programs, whose mission includes children's socialization, peer relations, and adaptive functioning, are uniquely positioned to support and promote children's healthy development. We propose that public sector mental health resources can be reallocated to support after school settings, and we offer specific examples and recommendations from an ongoing federally funded program of research to illustrate how mental health consultation can support publicly funded after school programs. In light of the increasing needs and depleting [corrected] resources of urban, poor communities, consultation to publicly funded after school programs can contribute to the mental health goals of keeping children safe and supervised, promoting their healthy development through academically and socially enriching activities, and identifying children in need of more intensive mental health services. PMID- 17340184 TI - Developing strategies to integrate peer providers into the staff of mental health agencies. AB - This study informs new strategies that promote integration of peer providers into the staff of social service agencies. Executive directors, human resource managers, supervisors and co-workers at 27 agencies in New York City were interviewed in-depth. Focus groups with peers were conducted. Consistent with previous research, respondents identified attitudes toward recovery, role conflict and confusion, lack of policies and practices around confidentiality, poorly defined job structure and lack of support as problems that undermined integration. Emerging from the data are strategies related to human resource policies and practices and workgroup relationships and operations that can improve employment of peer staff. PMID- 17340186 TI - Intervention effects on foster preschoolers' attachment-related behaviors from a randomized trial. AB - This study examined change in attachment-related behaviors among foster preschoolers participating in a randomized trial of the Multidimensional Treatment Foster Care Program for Preschoolers (MTFC-P). Measures of secure, resistant, and avoidant behaviors were collected using a caregiver-report diary at 3-month intervals during the 12 months following a new foster placement. Children randomly assigned to the MTFC-P intervention condition (n = 57) showed significant increases in secure behavior and significant decreases in avoidant behavior relative to children assigned to a regular foster care condition (n = 60). Both groups showed significant decreases in resistant behavior over time. Analyses also revealed a significant interaction between treatment condition and age at first foster placement on change in secure behavior. Results are discussed in terms of the importance of early intervention and prevention services for foster preschoolers. PMID- 17340185 TI - The beginning of the end: death signaling in early involution. AB - Mammary gland involution occurs in two distinct phases: an early, reversible phase, involving extensive apoptosis of the secretory alveolar epithelium without major changes in gland architecture, and a later, irreversible phase, involving remodelling of the gland to its pre-pregnancy state. Multiple signalling pathways are known to be important during early involution, however the precise triggers remain elusive. This review summarizes the roles of a number of key pathways (NF kappaB, PI(3)K, Stat3, and TGFbeta) in the first phase of involution. PMID- 17340187 TI - HIV/AIDS and immigrant Cape Verdean women: contextualized perspectives of Cape Verdean community advocates. AB - This research explored Cape Verdean community advocates' understandings of the structural and social realities that contribute to the increased HIV/AIDS risk of Northeastern U.S.-based immigrant Cape Verdean women. A community perspective informed the analysis of the multi-layered contextual barriers that these advocates identified as limiting the effectiveness of individual-level HIV/AIDS prevention and intervention models. Qualitative content analysis of interviews with nine community advocates revealed several thematic clusters including challenges to (1) perceived institutional and community realities; (2) traditional gender relations; and, (3) traditional ways of thinking. These findings challenge universalist cognitive-behavioral change models of HIV/AIDS prevention and intervention and are critically discussed to better understand the complex realities faced by Cape Verdean immigrant women. A liberatory community psychology perspective framed the research process and contributed to reconceptualizing HIV/AIDS risk as a community problem that requires interventions not simply at the individual and relational levels, but also at the structural level. PMID- 17340188 TI - Incidence and risk factors of neck discomfort: a 6-month sedentary-worker cohort study. AB - INTRODUCTION: This study aimed to evaluate the six-month incidence and possible risk factors of neck discomfort among sedentary workers. METHODS: Data, including demographic characteristics, work history, psychological characteristics and prevalent neck discomfort of 157 sedentary workers was collected by a questionnaire. A follow-up questionnaire was administered six months later to calculate the incidence of symptoms and related disability. RESULTS: The six month incidence of neck discomfort was 23.5% (12/51). The two groups of prevalent and non-prevalent subjects showed no difference in demographic data and work characteristics except for work load (p<0.05) and score in "job control" in the Job Content Questionnaire (JCQ) (p<0.05). In logistic regression, light-load work (versus no-load work, OR = 0.10, p = 0.023) and higher score of 'job control' in JCQ (OR = 0.86, p = 0.031) were significant protecting factors. CONCLUSION: The six-month incidence rates of neck discomfort in our subjects were high. Light load work and a higher score of 'job control' were important preventive factors. The results provide an epidemiological basis for prevention of neck discomfort in different working populations. PMID- 17340189 TI - Do we need pharmacological therapy for atrial fibrillation in the ablation era? AB - Management of atrial fibrillation (AF) remains one of the most difficult problems of modern cardiology. Pharmacological antiarrhythmic therapy is used both for termination of episodes of AF and for prevention of AF recurrences. Recently, major trials have compared the strategy of maintenance of sinus rhythm, called rhythm control, with the strategy of heart rate control during AF and found that the rhythm control strategy was not superior to rate control in terms of mortality. Although subsequent analysis identified rhythm control as a factor of improved survival, these large trials have markedly influenced the management of AF. One of the hypotheses explaining the non-superiority of the rhythm control strategy was that the benefit of sinus rhythm was offset by the side effects of antiarrhythmic agents. As a consequence, attention was directed to non pharmacological therapies, particularly to catheter ablation of the trigger or/and the atrial substrate using radiofrequency current or cryothermia. However, despite the reported good results of various types of interventions in the hands of highly qualified teams, catheter ablation cannot be applied to all patients with AF or to all types of AF. Furthermore, catheter ablation of AF requires sophisticated electrophysiologic laboratories equipped with expensive imaging techniques and a well-trained staff that cannot be available in sufficient number to cover the growing epidemic of AF with acceptable efficacy and safety even in rich countries. Therefore, there is still a need for pharmacological therapy aimed at the prevention of AF recurrences for the majority of AF patients. So far, attempts to provide the physician with efficient antiarrhythmic agents having a good safety profile have not been successful. However, recent research resulted in promising new approaches including prevention of AF using converting enzyme inhibitors or angiotensin 2 receptor blockers, new antiarrhythmic agents with multichannel effects such as dronedarone and tedisamil and atrial specific agents that theoretically should have no ventricular proarrhythmic effect as they target specific atrial channels such as I(KAch) and I(Kur) which are absent at the ventricular level. Other possible mechanisms of AF that represent potential targets, such as modification of stretch-activated ion channels, intervention of altered connexin expression and altered gap-junctional conductance, are currently investigated. PMID- 17340191 TI - Well-devised quantification analysis for duplication mutation of Duchenne muscular dystrophy aimed at preimplantation genetic diagnosis. AB - PURPOSE: Preimplantation genetic diagnosis (PGD) has been performed for deletion and point mutation type of Duchenne muscular dystrophy (DMD). Our aim was to develop a PGD technique, not yet established, to directly detect duplication mutation instead of substitute diagnosis similar to gender determination. METHODS: Our method is based on comparative quantification using conventional duplex PCR, real-time PCR and gender determination. We evaluated this method in single lymphocytes from a duplication type of DMD patient and a normal male. RESULTS: There was a significant difference in the mean values of the ratios (the mutation locus/a normal reference): mean value +/- SE was 1.84 +/- 0.15 in the duplication patient, and 1.00 +/- 0.09 in the normal male (p < 0.001). CONCLUSION: It is suggested that our comparative quantification method could be a new option in PGD for carriers with duplication mutation who wish to have an unaffected son. PMID- 17340190 TI - Pregnancy outcome and live birth after IVF and ICSI according to embryo quality. AB - PURPOSE: The pregnancy outcome and the chances of birth were assessed according to embryo quality after IVF or ICSI. METHODS: The implantation rate (IR), the loss of gestational sacs rate (LGSR), and birth rate (BR) were determined according to the cleavage stage and the integrity of blastomeres after day-2 homogeneous embryo transfers (n = 1812). RESULTS: The LGSR was higher after transfers of 2-3-cell or 5-6-cell embryos and was significantly increased when more than 20% of the embryo volume was fragmented in 4-cell embryos. After transfers of 4-cell embryos without fragmentation, the BR was significantly higher than the BR after transfers of 4-cell embryos with 1-20% fragmentation (16.6% vs 13.1%). The difference was the consequence of a higher IR (20.4% vs 17.3%) but also of a lower LGSR (18.9% vs 24.2%). CONCLUSIONS: Not only implantation and the ability to give a pregnancy, but also the capacity to give a live birth are dependent on the embryo quality. PMID- 17340192 TI - Vascular endothelial growth factor (VEGF) in autoimmune diseases. AB - Vascular endothelial growth factor (VEGF) is a potent stimulating factor for angiogenesis and vascular permeability. There are eight isoforms with different and sometimes overlapping functions. The mechanisms of action are under investigation with emerging insights into overlapping pathways and cross-talk between other receptors such as the neuropilins, which were not previously associated to angiogenesis. VEGF has important physiological actions on embryonic development, healing, and menstrual cycle. It also has a great role in pathological conditions that are associated to autoimmune diseases. There is considerable evidence in various autoimmune diseases such as in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis of an interrelationship between the VEGF system and theses disorders. Serum levels of VEGF correlate with disease activity in a large number of autoimmune diseases and fall with the use of standard therapy. We raised the possible future therapeutic strategies in autoimmune diseases with the anti-VEGF or anti-VEGFR (receptor). So far, this therapy has been used in cancer and macular ocular degeneration in diabetes. This review outlines the evidence for VEGF participation in various autoimmune diseases and proposes lines for future research in this field. PMID- 17340193 TI - Structural and functional properties of antibodies to the superantigen TSST-1 and their relationship to menstrual toxic shock syndrome. AB - Menstrual toxic shock syndrome (mTSS) is an acute febrile disease accompanied by hypotension and multiple organ involvement. Infection with Staphylococcus aureus producing the superantigen toxic shock syndrome toxin-1 (TSST-1) vaginally is necessary; however, only a small fraction of those infected with TSST-1 producing bacteria actually develop mTSS, suggesting that host factors modulate disease susceptibility. Serum antibodies to the toxin protect against development of the syndrome, but not all antibodies can neutralize the toxin. We set out to determine whether risk of developing the syndrome is related to the absence of neutralizing antibody and if antibody isotypes influence the neutralization capacity. In healthy subjects, TSST-1-binding serum antibodies were exclusively of the IgG and IgM classes; however, toxin-neutralizing capacity was correlated to the TSST-1-specific IgG1 and IgG4 antibodies (r (2)=0.88, p<0.0001 and 0.33, p<0.0086, respectively) but not with IgM antibodies. Specific IgA was not detectable. Compared to healthy matched controls who were colonized vaginally with S. aureus, IgG1 anti-TSST-1 antibodies and toxin neutralizing activity was lacking in all of the acute phases and in the majority of convalescent sera, suggesting that these patients may be incapable of generating TSST-1 neutralizing antibodies. These new findings support the hypothesis that host factors are important in the development of mTSS and that the anti-toxin isotype impacts antibody functionality. PMID- 17340194 TI - Electric fields around and within single cells during electroporation-a model study. AB - One of the key issues in electric field-mediated molecular delivery into cells is how the intracellular field is altered by electroporation. Therefore, we simulated the electric field in both the extracellular and intracellular domains of spherical cells during electroporation. The electroporated membrane was modeled macroscopically by assuming that its electric resistivity was smaller than that of the intact membrane. The size of the electroporated region on the membrane varied from zero to the entire surface of the cell. We observed that for a range of values of model constants, the intracellular current could vary several orders of magnitude whereas the maximum variations in the extracellular and total currents were less than 8% and 4%, respectively. A similar difference in the variations was observed when comparing the electric fields near the center of the cell and across the permeabilized membrane, respectively. Electroporation also caused redirection of the extracellular field that was significant only within a small volume in the vicinity of the permeabilized regions, suggesting that the electric field can only facilitate passive cellular uptake of charged molecules near the pores. Within the cell, the field was directed radially from the permeabilized regions, which may be important for improving intracellular distribution of charged molecules. PMID- 17340195 TI - Regulation of antioxidants and phase 2 enzymes by shear-induced reactive oxygen species in endothelial cells. AB - Exposure of vascular endothelial cells (ECs) to steady laminar shear stress activates the NF-E2-related factor 2 (Nrf2) which binds to the antioxidant response element (ARE) and upregulates the expression of several genes. The onset of shear is known to increase the EC reactive oxygen species (ROS) production, and oxidative stress can activate the ARE. ARE-regulated genes include phase 2 enzymes, such as glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), and antioxidants, such as glutathione reductase (GR), glutathione peroxidase (GPx) and catalase. We examined how shear stress affects the antioxidant/phase 2 enzyme activities and whether ROS mediate these effects. ROS production, measured by dichlorofluorescin fluorescence, depended on level and time of shear exposure and EC origin, and was inhibited by either an endothelial nitric oxide synthase (eNOS) inhibitor or a superoxide dismutase (SOD) mimetic and peroxynitrite (ONOO-) scavenger. Shear stress (10 dynes/cm2, 16 h) significantly increased the NQO1 activity, did not change significantly the glutathione (GSH) content, and significantly decreased the GR, GPx, GST and catalase activities in human umbilical vein ECs. Either eNOS inhibition or superoxide radical (O2*-)/ONOO- scavenging differentially modulated the shear effects on enzyme activities suggesting that the intracellular redox status coordinates the shear-induced expression of cytoprotective genes. PMID- 17340196 TI - Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells. AB - The success of ex vivo viral gene therapy systems for promoting bone formation could be improved through the development of systems to spatially localize gene expression. Towards this goal, we have encapsulated adenovirus-transduced human diploid fetal lung fibroblasts (MRC-5) expressing bone morphogenetic protein-type 2 (BMP-2) within non-degradable poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels and implanted these intramuscularly to promote endochondral bone formation. To optimize BMP-2 secretion, the molecular weight of the polymers and cell densities were varied. Polymers with molecular weights of 6, 10, and 20 kDa were used to prepare hydrogels containing 1, 5, or 10 million transduced cells. The results showed that 10 million transduced fibroblasts that was the maximum number of cells feasible for encapsulation within PEG-DA 10 and 20 kDa hydrogels produced the highest amount of secreted BMP-2 protein. Encapsulation of MRC-5 and transduced fibroblasts resulted in 71 and 58% cell viability, respectively. The bioactivity of secreted BMP-2 protein from the hydrogels was confirmed with an alkaline phosphatase assay. Micro-CT of the lower limb muscles of NOD/SCID mice following implantation with hydrogels showed 39.5 +/- 25.0 mm3 mineralized tissue and 31.8 +/- 7.8 mm3 for the cell-injected mice, and the bone was localized to the hydrogel surfaces. Histology revealed bone as well as cartilage for both hydrogel implanted and cell-injected animals. PMID- 17340197 TI - Kinetic modeling of contrast-enhanced MRI: an automated technique for assessing inflammation in the rheumatoid arthritis wrist. AB - In recent years, development of rheumatoid arthritis (RA) drug therapy has been more directly targeted to counteract specific mechanisms of inflammation, and it is now believed that early aggressive treatment with disease modifying drugs is important to inhibit future structural joint damage. The development of these new treatments has increased the need for methodologies to assess disease activity in RA and monitor the effectiveness of drug therapy. Unlike X-ray, which shows only structural bone damage, magnetic resonance imaging (MRI) can depict soft tissue damage and synovitis, the primary pathology of RA. Recent studies have also indicated that MRI is sensitive to pathophysiologic changes that may predate radiographic erosions and may predict future joint damage. In this study, we have developed a computer automated analysis technique for MR wrist images that provides an objective measure of RA synovitis. This method applies a two compartment pharmacokinetic model to every voxel of a dynamic contrast-enhanced MRI (DCE-MRI) dataset and outputs resulting parametric images. The aim of this technique is to not only objectively quantify the severity of rheumatoid synovitis, but to also locally determine where areas of serious disease activity are situated through kinetic modeling of blood-tissue exchange. Preliminary results show good correlation to early enhancement rate, which has previously been shown to be a useful clinical marker of RA activity. However, the use of tracer kinetic modeling methods potentially provides more specific information regarding underlying RA physiology. This approach could provide a useful new tool in RA patient management and could substantially improve RA therapeutic studies by calculating objective biomarkers of the disease state. PMID- 17340198 TI - Structural differences between the putative carbohydrate-recognition domains of human IL-1 alpha, IL-1 beta and IL-1 receptor antagonist obtained by in silico modeling. AB - In a previous report (Cebo et al. J Biol Chem 276 (2001) 5685-5691), it was established that biologically active recombinant human IL-1alpha and IL-1beta had different carbohydrate-binding properties. IL-1alpha recognized a di-antennary N glycan with two alpha2-3-linked sialic acid residues, whereas IL-1beta recognized the GM(4), a alpha2-3-linked sialylated glycosphingolipid. These different carbohydrate-binding properties of two interleukins binding to the same receptor (IL-1R) could explain why these molecules had different biological effects and cell specificities. Molecular modeling of the ligands and in silico docking experiments defined putative carbohydrate-recognition domains localized in the same area of the two molecules, a domain different from that defined as the type I IL-1R binding domain. The calculated pattern of hydrogen bonding and of van der Waals interactions fulfilled the essential features observed for calcium independent lectins (mammalian, viral or bacterial). The analysis of the same domain of the third members of this family of molecules, the IL-1R-antagonist, indicated it did not fulfill the criteria for carbohydrate-recognition domains. It is proposed that its role as a pure antagonist is due to the absence of lectin activity and consequently explained its inability to associate IL-1R with other surface molecular complexes necessary for signaling. PMID- 17340199 TI - Brief report: aggression and stereotypic behavior in males with fragile X syndrome--moderating secondary genes in a "single gene" disorder. AB - Although fragile X syndrome (FXS) is a single gene disorder with a well-described phenotype, it is not known why some individuals develop more significant maladaptive behaviors such as aggression or autistic symptoms. Here, we studied two candidate genes known to affect mood and aggression, the serotonin transporter (5-HTTLPR) and monoamine oxidase A (MAOA-VNTR) polymorphisms, in 50 males with FXS ages 8-24 years. Mothers and fathers of participants reported the frequency and severity of aggressive/destructive, self-injurious, and stereotypic behaviors. Polymorphism genotypes were unrelated to age and IQ. Results showed a significant effect of 5-HTTLPR genotype on aggressive/destructive and stereotypic behavior; males with FXS who were homozygous for the high-transcribing long (L/L) genotype had the most aggressive and destructive behavior, and individuals homozygous for the short (S/S) genotype had the least aggression. Those with the L/L genotype also had the highest levels of stereotypic behavior. There was no effect of MAOA-VNTR on behavior; however those with the high-activity, 4-repeat genotype were more likely to be taking SSRI or SNRI medication. This preliminary study prompts consideration of secondary genes that may modify behavioral phenotype expression in neurodevelopmental disorders, even those with a single gene etiology such as FXS. PMID- 17340200 TI - Asperger syndrome and autism: a comparative longitudinal follow-up study more than 5 years after original diagnosis. AB - Prospective follow-up study of 70 males with Asperger syndrome (AS), and 70 males with autism more than 5 years after original diagnosis. Instruments used at follow-up included overall clinical assessment, the Diagnostic Interview for Social and Communication Disorders, Wechsler Intelligence Scales, Vineland Adaptive Behavior Scales, and Global Assessment of Functioning Scale. Specific outcome criteria were used. Outcome in AS was good in 27% of cases. However, 26% had a very restricted life, with no occupation/activity and no friends. Outcome in the autism group was significantly worse. Males with AS had worse outcomes than expected given normal to high IQ. However, outcome was considerably better than for the comparison group of individuals with autism. PMID- 17340201 TI - Sleep in children with Asperger syndrome. AB - The prevalence of sleep disturbances in 52 children with Asperger syndrome (AS) as compared with 61 healthy controls (all subjects aged 5-17 years) was investigated. Problems with sleep onset and maintenance, sleep-related fears, negative attitudes toward sleeping, and daytime somnolence were more frequent among children with AS than among controls. Short sleep duration (<9 h) was almost twofold (59% vs. 32%), and the risk for sleep onset problems more than fivefold (53% vs. 10%) more common in the AS group than in the control group. Child-reported sleeping problems were also more prevalent in the AS group than in controls (58% vs. 7%). The results suggest that sleep disturbances should be routinely evaluated in children with AS. PMID- 17340202 TI - Arousal modulation in females with fragile X or Turner syndrome. AB - The present study was carried out to examine physiological arousal modulation (heart activity and skin conductance, across baseline and cognitive tasks, in females with fragile X or Turner syndrome and a comparison group of females with neither syndrome. Relative to the comparison group, for whom a greater increase in skin conductance was associated with poor arithmetic performance and less risk taking behavior, females with fragile X displayed a minimal increase in heart activity that was nevertheless associated with poor performance on mental arithmetic. In contrast, no arousal-cognitive performance relationship emerged for the group with Turner syndrome. Taken together, our findings suggest that distinct profiles of arousal modulation might be associated with cognitive deficits in these syndrome populations. PMID- 17340203 TI - The G22A polymorphism of the ADA gene and susceptibility to autism spectrum disorders. AB - Inborn errors of purine metabolism have been implicated as a cause for some cases of autism. This hypothesis is supported by the finding of decreased adenosine deaminase (ADA) activity in the sera of some children with autism and reports of an association of the A allele of the ADA G22A (Asp8Asn) polymorphism in individuals with autism of Italian-descent. We tested the ADA G22A polymorphism in 126 North American affected sib-pair families but found no aberrant allele distributions in cases versus controls. Instead, we found an increased transmission of the G allele from fathers to affected children. Our findings suggest that the ADA G22A polymorphism plays a minimal role in susceptibility to autism in North American families. PMID- 17340204 TI - Predictors of preventive health care use among middle-aged and older adults in Mexico: the role of religion. AB - Research has shown that religion is associated with a wide range of health behaviors among adults of all ages. Although there is strong support for religion's influence on behaviors such as drinking and smoking, less is known about the possible relationship between religion and the use of preventive health services. This relationship may be particularly important in Mexico, a country with high levels of religiousness and low levels of preventive service utilization. The current study uses a nationally representative sample of middle aged and older adults in Mexico (n = 9,890) to test the association between three facets of religion and three preventive services aimed at detecting chronic conditions or underlying risk factors. The findings show that religious salience is significantly related to the use of blood pressure and cholesterol screenings, even after controlling for a variety of social, demographic, and health-related factors. In addition, attending religious services and participating in religious activities are both positively associated with blood pressure and diabetes screening. This type of research adds to our knowledge of the determinants of preventive service utilization, as well as to the burgeoning literature on religion and health. Furthermore, because the vast majority of research in this field takes place in more developed and Westernized countries, such as the US and Western Europe, analyzing this relationship in a sample of older Mexicans is critical for providing the field with a more comparative orientation. PMID- 17340205 TI - NMR solution structure of the reduced form of thioredoxin 2 from Saccharomyces cerevisiae. PMID- 17340206 TI - Rapid and accurate processing method for amide proton exchange rate measurement in proteins. AB - Exchange between protein backbone amide hydrogen and water gives relevant information about solvent accessibility and protein secondary structure stability. NMR spectroscopy provides a convenient tool to study these dynamic processes with saturation transfer experiments. Processing of this type of NMR spectra has traditionally required peak integration followed by exponential fitting, which can be tedious with large data sets. We propose here a computer aided method that applies inverse Laplace transform in the exchange rate measurement. With this approach, the determination of exchange rates can be automated, and reliable results can be acquired rapidly without a need for manual processing. PMID- 17340207 TI - Active integration: new strategies for transgenesis. AB - This paper presents novel methods for producing transgenic animals, with a further emphasis on how these techniques may someday be applied in gene therapy. There are several passive methods for transgenesis, such as pronuclear microinjection (PNI) and Intracytoplasmic Sperm Injection-Mediated Transgenesis (ICSI-Tr), which rely on the repair mechanisms of the host for transgene (tg) insertion. ICSI-Tr has been shown to be an effective means of creating transgenic animals with a transfection efficiency of approximately 45% of animals born. Furthermore, because this involves the injection of the transgene into the cytoplasm of oocytes during fertilization, limited mosaicism has traditionally occurred using this technique. Current active transgenesis techniques involve the use of viruses, such as disarmed retroviruses which can insert genes into the host genome. However, these methods are limited by the size of the sequence that can be inserted, high embryo mortality, and randomness of insertion. A novel active method has been developed which combines ICSI-Tr with recombinases or transposases to increase transfection efficiency. This technique has been termed "Active Transgenesis" to imply that the tg is inserted into the host genome by enzymes supplied into the oocyte during tg introduction. DNA based methods alleviate many of the costs and time associated with purifying enzyme. Further studies have shown that RNA can be used for the transposase source. Using RNA may prevent problems with continued transposase activity that can occur if a DNA transposase is integrated into the host genome. At present piggyBac is the most effective transposon for stable integration in mammalian systems and as further studies are done to elucidate modifications which improve piggyBac's specificity and efficacy, efficiency in creating transgenic animals should improve further. Subsequently, these methods may someday be used for gene therapy in humans. PMID- 17340208 TI - The investigation of GSTT1, GSTM1 and SOD polymorphism in bladder cancer patients. AB - Glutathione S transferases (GSTT1, GSTM1, GSTP1) are enzymes that activate the detoxification of endogenous and exogenous agents. The genetic polymorphism in these genes may change the response of individuals to environmental toxicants. The genetic polymorphisms of GSTT1, GSTM1, GSTP1 have been studied extensively in the determination of individual cancer risks. Some studies showed a strong relationship between polymorphism of GSTs and superoxidedismutase enzymes. Using the polymerase chain reaction (PCR) the prevalence of genetic polymorphisms of GSTT1, GSTM1 and MnSOD (Manganese Superoxide Dismurase) was investigated in 104 cases and controls to seek any association with the risk of bladder cancer. The frequency of GSTT1 +/+ polymorphism was 65% (33/51) in the cases and 79% (42/53) in the controls. The frequency of the GSTM1 +/+ polymorphism was 33% (17/51) in the cases and 58% (31/53) in the controls. The frequency of the GSTM1 null genotype was 42% (22/53) in the controls and 68% (34/51) in the patients. The frequency of the SOD AA genotype was 36% (17/51) in the cases and 33% (19/53) in the controls. There was no association between the GSTT1 and SOD polymorphism and bladder cancer incidence. The incidence of the GSTM1 null genotype was increased in bladder cancer patients compared to controls (OR = 1.755, 95% CI = 1.119 2.751). PMID- 17340209 TI - Urethral sensory threshold and urethro-anal reflex latency in continent women. AB - AIMS OF STUDY: The sensory evaluation of the lower urinary tract is summarized in the bladder proprioceptive sensitivity during cystometry. Experimental studies suggest that abnormalities of the urethral innervation and micturition reflex can be related to the presence of continence disturbances. This study aimed to measure the urethral sensory threshold and the urethro-anal reflex latency in healthy volunteers, establishing reading criteria, comparing the results and technique used with the literature and verifying the effect of physiological factors. MATERIALS AND METHODS: Thirty healthy female volunteers were studied. They had an absence of genital or urinary complaints and had undergone no previous pelvic or vaginal procedures. The measurement of the urethral sensory threshold and urethro-anal reflex latency were performed as described. RESULTS: The determination of the urethral sensory threshold and urethro-anal reflex latency were obtained in 96.6% of the volunteers. The electrophysiological parameters did not correlate with age, parity or number of vaginal deliveries. There was a positive association of the urethral sensory threshold with height. Technical aspects were considered and compared with those in the literature as well as the advantages and limitations of the method. CONCLUSIONS: The measurement of the urethral sensory threshold and urethro-anal reflex latency presented consistent recordings. The urethral sensory threshold should be analyzed carefully in individuals with height above the population average. Subsequent observations are necessary to clarify their function in patients with continence disturbances and to measure the urethral function, but these values can be used as normal parameters for comparison. PMID- 17340210 TI - The relationship between the expression of E-cadherin and tumor recurrence and progression in high-grade stage T1 bladder urothelial carcinoma. AB - OBJECTIVE: To evaluate the relationship between the expression of E-cadherin (E CD) and tumor recurrence and progression in patients with high-grade stage T1 urothelial carcinoma of bladder. METHODS: Fifty-two patients who had primary high grade stage T1 urothelial carcinoma were enrolled to the study. The pathologic specimens of patients were evaluated and staged as T1a and T1b according to muscularis mucosae involvement by the tumor. The immunohistochemical demonstration of E-CD was accomplished by using immunoperoxidase method and all the specimens were examined under light microscope for E-CD level. RESULTS: The mean age of the patients was 64.0 +/- 7.7 (range 36-81) years. The mean follow-up period was 56.4 +/- 19.4 (range 14-84) months. Among 52 patients, 27 (52%) of them were stage T1b and 25 (48%) were T1a tumors. The recurrence rates for T1a and T1b groups were 52% (n = 13) and 92.6% (n = 25), respectively (P < 0.05). The expression of E-CD was homogenous in 52% of pT1a and 14.8% of T1b tumors (P < 0.05). In T1a group with recurrence, homogeneous E-CD staining ratio was 30.7% (n = 4/13), but it was 75% (n = 9/12) in T1a patients without recurrence (P < 0.05). In T1b group with recurrence, the homogenous expression of E-CD was 12% (n = 3/25) and the expression of E-CD was heterogenous in 88% (n = 22/25) of them (P < 0.05). In T1a group, progression of the disease was detected in 28% (n = 7/25) of the patients, but disease progression was seen in 55.5% (n = 15/27) of T1b group patients (P < 0.05). In T1a group with progression, heterogeneous E-CD staining ratio was 85.7% (n = 6/7), but it was 80% (n = 12/15) in T1b patients with progression. The effects of tumor number, tumor size and carcinoma in situ presence on recurrence were evaluated within each group. It was determined that parameters such as tumor number and tumor size had no significant effect on recurrence of the groups. The mean survival rates were statistically different between the groups. On multivariate analysis only E-cadherin expression (P = 0.012, odds ratio 6.291, 95% confidence interval for odds ratio 1.303-4.72) and tumor stage (P = 0.003, odds ratio 11.58, 95% confidence interval for odds ratio 2.446-8.542) remained independently significant as predictors of recurrence. CONCLUSION: E-CD expression was decreased in pathologic specimens of bladder tumor patients with muscularis mucosae involvement and this condition correlated well with tumor recurrence. PMID- 17340211 TI - Vascular permeability in ocular disease and the role of tight junctions. AB - Vascular permeability is closely linked with angiogenesis in a number of pathologies. In the retina, the normally well-developed blood-retinal barrier is altered in a host of eye diseases preceding or commensurate with angiogenesis. This review examines the literature regarding the tight junction complex that establishes the blood-retinal barrier focusing on the transmembrane proteins occludin and the claudin family and the membrane associated protein zonula occludens. The changes observed in these proteins associated with vascular and epithelial permeability is discussed. Finally, novel literature addressing the link between the tight junction complex and angiogenesis is considered. PMID- 17340212 TI - A relativistic neutron fireball from a supernova explosion as a possible source of chiral influence. AB - We elaborate on a previously proposed idea that polarized electrons produced from neutrons, released in a supernova (SN) explosion, can cause chiral dissymmetry of molecules in interstellar gas-dust clouds. A specific physical mechanism of a relativistic neutron fireball with Lorentz factor of the order of 100 is assumed for propelling a great number of free neutrons outside the dense SN shell. A relativistic chiral electron-proton plasma, produced from neutron decays, is slowed down owing to collective effects in the interstellar plasma. As collective effects do not involve the particle spin, the electrons can carry their helicities to the cloud. The estimates show high chiral efficiency of such electrons. In addition to this mechanism, production of circularly polarized ultraviolet photons through polarized-electron bremsstrahlung at an early stage of the fireball evolution is considered. It is shown that these photons can escape from the fireball plasma. However, for an average density of neutrals in the interstellar medium of the order of 0.2 cm(-3) and at distances of the order of 10 pc from the SN, these photons will be absorbed with a factor of about 10( 7) due to the photoeffect. In this case, their chiral efficiency will be about five orders of magnitude less than that for polarized electrons. PMID- 17340213 TI - Differential response of chloride binding sites to elevated temperature: a comparative study in spinach thylakoids and PSII-enriched membranes. AB - A study of heat effects was performed in thylakoids and photosystem II (PSII) enriched membranes isolated from spinach in relation to Cl(-)-induced activation of PSII catalyzed oxygen evolution and the retention of Cl(-) in the PSII complex. For this, Cl(-)-sufficient membranes and low-Cl(-) membranes were used. The presence of Cl(-) in the reaction medium did accelerate oxygen evolution, which remained unaffected by heat treatment up to 40 degrees C in PSII membranes and up to 42.5 degrees C in thylakoids. Heat resistance of Cl(-)-induced activation of oxygen evolution was found to be independent of the presence of 'bound Cl(-)' in the preparations. However, the functional stability of the PSII complex during heat treatment showed a marked dependence on the presence of bound Cl(-) in PSII. Electron paramagnetic resonance study of manganese (Mn) release per reaction center/Y (D) (+) showed that there was little loss of Mn(2+) up to 42 degrees C in our preparations, although the PSII activity was significantly lowered. These observations together with data from steady state chlorophyll a fluorescence imply that the site of action of Cl(-) causing direct activation of oxygen evolution was different from the site of primary heat damage. A differential response of chloride binding sites to heat stress was observed. The high-affinity (tightly bound, slow exchanging) site of chloride is affected earlier ( approximately 37 degrees C) while low-affinity (loosely bound, fast exchanging) site gets affected at higher temperatures (42.5 degrees C in thylakoids and 40 degrees C in the case of PSII-enriched membranes). PMID- 17340214 TI - A template for the future: digitizing and databasing a taxonomic illustration collection. AB - This is the first iconographic taxonomic database intended as an everyday tool for the practising taxonomist, that allows access to the original drawings used to describe species. We demonstrate the system with water mites (Acari, Parasitengona, Hydrachnidia) but it may be used with any other plant or animal group. Query by genus or species leads to the original drawings and any additional images associated to that particular name. At present, the database includes images from more than 4,000 species (around 38,000 illustrations) and is easily expandable. Copyright does not allow the database to be used in an open WWW context, but it can be an extremely useful tool in private taxonomic applications. PMID- 17340215 TI - Further evidence for geographic differentiation in R. appendiculatus (Acari: Ixodidae) from Eastern and Southern provinces of Zambia. AB - Studies in the biology, ecology and behaviour of R. appendiculatus in Zambia have shown considerable variation within and between populations often associated with their geographical origin. We studied variation in the mitochondrial COI (mtCOI) gene of adult R. appendiculatus ticks originating from the Eastern and Southern provinces of Zambia. Rhipicephalus appendiculatus ticks from the two provinces were placed into two groups on the mtCOI sequence data tree. One group comprised all haplotypes of specimens from the Eastern province plateau districts of Chipata and Petauke. The second group consisted of a single haplotype of specimens from the Southern province districts and Nyimba, an Eastern province district on the fringes of the valley. This variation provides additional evidence to the earlier observations in the 12S rDNA and ITS2 data for the geographic subdivision of R. appendiculatus from Southern province and Eastern province plateau. The geographic subdivision further corresponds with differences in body size and diapause between R. appendiculatus from these geographic areas. The possible implications of these findings on the epidemiology of East Coast fever (ECF) the disease for which R. appendiculatus is one of the vectors are discussed. PMID- 17340216 TI - Utility of lumbar puncture in diagnosis of Vogt-Koyanagi-Harada disease. AB - PURPOSE: To determine the significance of lumbar puncture in diagnosis of Vogt Koyanagi-Harada disease (VKH). METHOD: A retrospective analysis was conducted on 116 consecutive patients diagnosed with VKH. Two additional patients who presented with acute VKH were included in the analysis. Demographic characteristics, including gender, age, and ethnicity, were extracted from the medical record. The stage of disease at presentation was documented. Pertinent laboratory results and diagnostic procedures such as lumbar puncture, fluorescein angiography, and echography that contributed to the diagnosis of VKH were collected. RESULTS: Lumbar puncture results for 10 patients were available. Eight of these patients presented with pleocytosis consistent with a diagnosis of VKH. Clinical features and fluorescein angiography confirmed the diagnosis in these patients. Both of the patients who did not exhibit cerebrospinal fluid (CSF) pleocytosis presented with headache, vision loss, and bilateral uveitis. Fluorescein angiography disclosed multiple foci of leakage at the retinal pigment epithelium level with accumulation of dye under the retina and disc leakage, confirming diagnosis of VKH. CONCLUSION: The utility of lumbar puncture as a diagnostic criterion for VKH should be re-evaluated given that clinical features and fluorescein angiography alone often support the diagnosis. The inherent risks and complications associated with the procedure must prompt the clinician to reserve this evaluation for atypical presentations. PMID- 17340217 TI - Vertebral dimensions as risk factor of vertebral fracture in osteoporotic patients: a systematic literature review. AB - This systematic literature review studied the potential association between vertebral fracture risk and vertebral dimensions. Analysis showed that patients with vertebral fractures have smaller non-fractured vertebrae than patients without fractures. Vertebral size is an independent risk factor of vertebral fractures. INTRODUCTION: Biomechanical factors such as vertebral dimensions may be a risk factor for vertebral fractures beside bone mineral density (BMD). The objective of this study was to evaluate potential association of vertebral size and shape with osteoporotic fracture risk through a systematic literature review. METHODS: Systematic analysis of published reports comparing vertebral dimensions of patients with and without osteoporotic fractures was performed. Data sources were electronic databases. Data extraction included methods, site, reproducibility and results of vertebral measurement, study population characteristics. It was noted if populations were matched or data were adjusted for age, height, weight and BMD. RESULTS: Of 634 reports identified by the literature search, the final review included 13 reports studying 4,428 women and 508 men; median age 64.2 years [range 51.7%-73.0%]. Measurements were performed with computed tomography scan, X-ray, or dual energy X-ray absorptiometry. Vertebral body height, width, depth, area, cross-sectional area (CSA), and volume were 5.5% to 9.5% smaller in fractured group than control group. After adjustment for confounding factors, area, CSA and volume were, respectively, 10.2% [range 7.1%-13.3%], 7.7% [range 1.2%-14.2%] and 9.5% [8.5%-10.5%] smaller in fractured group. CONCLUSIONS: Vertebral size should be considered as a potential independent vertebral fracture risk factor. PMID- 17340218 TI - Correlation of plain radiographic indices of the hip with quantitative bone mineral density. AB - Radiographic parameters of the hip can be useful as an indication of bone mineral density at the femoral neck. Measurements available from routine hip radiographs were correlated with DXA values. Although radiographs are not a test for osteoporosis, measurements of cortical thickness provide information useful for referral for osteoporosis assessment. INTRODUCTION: Plain hip radiographs are widely used for evaluation of hip pathology in osteoarthritis. A purpose of this study was to determine whether there are relationships between radiographic parameters of bone structure and bone mineral density T-scores, as assessed by dual energy x-ray absorptiometry (DXA). METHODS: Pre-operative radiographs of 32 postmenopausal, osteoarthritic women undergoing hip arthroplasty were evaluated. Radiographic parameters including the Singh index, Dorr classification, canal-to calcar ratio, and cortical thickness indices (CTI) were measured and compared with T-score, serum 25 hydroxyvitamin D levels, body mass index (BMI), and body weight. RESULTS: The T-score at the femoral neck for type C bone was significantly lower than that of type A (p = 0.041). The CTIs were correlated positively with T-scores for anteroposterior radiographs (r = 0.5814, p = 0.0005), and for lateral radiographs (r = 0.571, p = 0.0006). A threshold for lateral CTI set at a value of < or =0.40 results in sensitivity of 0.85 and specificity of 0.79 to segregate the osteoporotic and non-osteoporotic patients. CONCLUSION: Femurs with small radiographic cortical thickness indices had lower T scores. Finding a radiographic hip cortical thickness index (LAT) with a value of < or =0.40 should be an alert for referral for osteoporosis evaluation and bone mineral density testing. PMID- 17340219 TI - Race/ethnic differences in bone mineral density in men. AB - The epidemiology of osteoporosis in male and minority populations is understudied. We compared BMD in 1,209 Black, Hispanic, and White men. Black men exhibited higher BMD than Hispanic or White men. Age-related BMD decreases were greatest among Hispanic men. Results may help explain variation in hip fracture rates by race/ethnicity. INTRODUCTION: The epidemiology of osteoporosis in male and minority populations is understudied. To address this concern, we conducted a study of skeletal health in a diverse population of adult males. METHODS: A total of 367 Black, 401 Hispanic, and 451 White men aged 30-79 years were randomly sampled from Boston, MA. Bone densitometry (bone area (BA), bone mineral content (BMC), and bone mineral density (BMD)) at the whole body, hip, lumbar spine, and forearm was performed. Multiple regression analyses on 1,209 men with available data were used to describe race/ethnic group-specific means (height- and age adjusted) and age trends (height-adjusted) in BMC, BA, and BMD. Results were weighted to represent the Boston male population aged 30-79 years. RESULTS: Black men had greater BMC and BMD than Hispanic or White men. Femoral neck BMD was 5.6% and 13.3% higher in Black men than in Hispanic and White men, respectively. Differences between Hispanic and White subjects were restricted to the hip. Age related declines in BMC and BMD were significantly steeper among Hispanic than Black or White men. CONCLUSIONS: Differences in BMC and BMD could explain variation in fracture rates among Black, Hispanic, and White men. The steeper age related BMD decline in Hispanic men is of particular concern. PMID- 17340220 TI - Promoting R & D in photobiological hydrogen production utilizing mariculture raised cyanobacteria. AB - This review article explores the potential of using mariculture-raised cyanobacteria as solar energy converters of hydrogen (H(2)). The exploitation of the sea surface for large-scale renewable energy production and the reasons for selecting the economical, nitrogenase-based systems of cyanobacteria for H(2) production, are described in terms of societal benefits. Reports of cyanobacterial photobiological H(2) production are summarized with respect to specific activity, efficiency of solar energy conversion, and maximum H(2) concentration attainable. The need for further improvements in biological parameters such as low-light saturation properties, sustainability of H(2) production, and so forth, and the means to overcome these difficulties through the identification of promising wild-type strains followed by optimization of the selected strains using genetic engineering are also discussed. Finally, a possible mechanism for the development of economical large-scale mariculture operations in conjunction with international cooperation and social acceptance is outlined. PMID- 17340221 TI - Changes in bone mass, bone structure, bone biomechanical properties, and bone metabolism after spinal cord injury: a 6-month longitudinal study in growing rats. AB - Spinal cord injury (SCI) results in a great decline in bone mineral density (BMD) and deterioration of bone microarchitecture. The objective of this study was to investigate the time course of the changes in BMD, microarchitecture, biomechanical properties, and bone turnover in male growing rats following SCI. Sixty male growing Sprague-Dawley rats, 6 weeks of age, were randomly divided into SCI (lower thoracic cord transection) and sham-operated groups, and bone tissues and blood samples were examined at 3 weeks, 6 weeks, and 6 months after surgery. SCI rats had low bone weight (wet, dry, and ash weight) and BMD of the femora, tibiae, and third lumbar vertebrae at all time points compared to sham rats, while in forelimbs, there was a decrease of dry and ash weight compared to sham rats only at 3 weeks but not BMD. Bone microarchitecture and trabecular connectivity were deteriorated in SCI rats and remained so after. Bone formation rate and serum osteocalcin level in SCI rats were significantly increased 3 weeks after SCI surgery. However, eroded surface/bone surface and serum N-terminal telopeptide of type I collagen level remained elevated from 3 weeks to 6 months. In addition, SCI rats showed poor biomechanical properties in the proximal tibiae and femora but not in the humeri. In conclusion, SCI causes profound BMD loss, disturbances in bone microarchitecture, decreased mechanical strength in the lower extremity and lumbar spine, and high bone turnover. These findings will allow better understanding of osteoporosis following SCI. PMID- 17340222 TI - Burden of hip fracture in Iran. AB - To measure the burden caused by hip fracture in Iran and to compare it with other parts of the world, we applied the Global Burden of Disease (GBD) method created by the World Health Organization. The GBD method uses disability-adjusted life years (DALY), which is comprised of years of life lost (YLL) and years of life lived with disability (YLD). To calculate YLD, incidence of hip fracture was obtained from the Iranian Multicenter Study on Accidental Injuries, a large-scale nationwide prospective study. Disability weights were applied to the remaining duration of disease. To calculate YLL, remaining years of potential life at any age at death were calculated using the standard life table. A discount rate of 3% and age weighting were applied. Hip fracture generated 16,708 DALYs, comprising 8,812 (52.7%) YLL and 7,896 (47.3%) YLD. Iran accounted for 0.85% of the global burden of hip fracture and 12.4% of the burden of hip fracture in the Middle East. The female to male ratio in Iran (1.1) was lower than the global (2.2) and the Middle Eastern (1.4) ratios and higher than the ratios in China and India (1.0 and 0.9, respectively). In conclusion, hip fracture is not as much a cause of disease burden in Iran as in the developed regions of the world. We recommend utilization of the standardized GBD method to calculate burden of osteoporosis in different countries and to set local priorities according to these measures. PMID- 17340223 TI - Expression and role of interleukin-6 in distraction osteogenesis. AB - Distraction osteogenesis is a special form of bone healing in which well controlled distraction stresses and consequent tensile strains within callus tissue induce very efficient new bone formation. Proinflammatory cytokines are involved during the early phase of fracture healing and callus remodeling. Temporal expression patterns of proinflammatory cytokines were assessed in Sprague-Dawley rat tibial models of distraction osteogenesis and acute lengthening, and only interleukin-6 (IL-6) was found to be specifically induced during the distraction phase. IL-6 immunoreactivity was detected not only in hemopoietic cells and osteoblasts but also in the spindle-shaped cells of the fibrous interzone, where most of the tensile strains are concentrated. In vitro study revealed that IL-6 did not affect the proliferation of C3H10T1/2 cells, mouse bone marrow stromal cells (MSCs), or MC3T3-E1 cells; but its blocking antibody reduced the proliferation of C3H10T1/2 cells and MSCs. The mRNA expression of COL1A1 and osteopontin were not changed by IL-6 or its blocking antibody, but the alkaline phosphatase activities of MC3T3-E1 cells were increased by IL-6 and decreased by its blocking antibody. These findings indicate that IL-6 is a proinflammatory cytokine that responds to tensile strain during distraction osteogenesis. IL-6 negatively affects the proliferation of primitive mesenchymal cells, whereas the differentiation of more mature osteoblastic lineage cells is enhanced by IL-6 in vitro. IL-6 appears to be one of the cytokines involved in the complex network of signal cascades evoked during distraction osteogenesis and may differentially affect immature and mature osteoblastic lineage cells. PMID- 17340224 TI - Strontium administration in young chickens improves bone volume and architecture but does not enhance bone structural and material strength. AB - Genetic selection for rapid body growth in broiler chickens has resulted in adverse effects on the skeletal system exemplified by a higher rate of cortical fractures in leg bones. Strontium (Sr) has been reported to have beneficial effects on bone formation and strength. We supplemented the diet of 300-day-old chicks with increasing dosages of Sr (0%, 0.12%, or 0.24%) to study the capacity of the element to improve bone quality and mechanical integrity. Treatment with Sr increased cortical bone volume and reduced bone porosity as measured by micro computed tomography. The higher level of Sr significantly reduced bone Ca content (34.7%) relative to controls (37.2%), suggesting that Sr replaced some of the Ca in bone. Material properties determined by the three-point bending test showed that bone in the Sr-treated groups withstood greater deformation prior to fracture. Load to failure and ultimate stress were similar across groups. Our results indicate that Sr treatment in rapidly growing chickens induced positive effects on bone volume but did not improve the breaking strength of long bones. PMID- 17340225 TI - Insulin-like effects of visfatin on human osteoblasts. AB - Visfatin (also known as pre-B cell colony-enhancing factor or PBEF) is a novel adipocytokine that is highly expressed in visceral fat and upregulated in obesity and type 2 diabetes mellitus. Visfatin binds to and activates the insulin receptor (IR), thereby exerting insulin-mimetic effects in various cell lines. IR has been detected in osteoblasts, which is consistent with the role of insulin as an important osteotropic hormone. This study investigated the actions of visfatin on human primary osteoblasts. The expression and tyrosine phosphorylation of IR, IR substrate-1 (IRS-1), and IRS-2 were determined by immunoprecipitation and immunoblotting. Cell proliferation was determined by measuring [(3)H]thymidine incorporation and cell number. Glucose uptake was determined by measuring 2 [(3)H]deoxyglucose incorporation. Real-time quantitative reverse-transcription polymerase chain reaction (PCR) was used for determining alkaline phosphatase (ALP), osteocalcin, and type I collagen mRNA expression. Enzyme-linked immunosorbent assay and radioimmunoassay were used for measuring ALP activity, osteocalcin secretion, and type I collagen production. We found that visfatin induced tyrosine phosphorylation of IR, IRS-1, and IRS-2. Moreover, the effects of visfatin - glucose uptake, proliferation, and type I collagen enhancement of cultured human osteoblast-like cells - bore a close resemblance to those of insulin and were inhibited by hydroxy-2-naphthalenylmethylphosphonic acid tris acetoxymethyl ester, a specific inhibitor of IR tyrosine kinase activity. We also unexpectedly found that visfatin downregulated osteocalcin secretion from human osteoblast-like cells. These data indicate that the regulation of glucose uptake, proliferation, and type I collagen production by visfatin in human osteoblasts involves IR phosphorylation, the same signal-transduction pathway used by insulin. PMID- 17340226 TI - Effect of voxel size on 3D micro-CT analysis of cortical bone porosity. AB - This study examines the impact of voxel size on 3D micro-CT analysis of human cortical bone porosity. The study is based on computed microtomography scans of 10 human anterior femoral midshaft specimens acquired at 5, 10, and 15 microm voxel sizes. Artificial voxel sizes (10, 20, and 40 microm) were generated from the smallest scan voxel size (5 microm) in order to compare actual scanning with artificial degradation, a method employed in other similar studies. Canal volume fraction (CaV/TV), canal surface to volume ratio (CaS/CaV), mean canal diameter (CaDm), mean canal separation (CaSp), canal number (CaN), degree of anisotropy (DA), and canal connectivity density (CaConnD) were calculated from matching volumes of interest for all datasets. Qualitatively, the clarity of the actual scan datasets deteriorated rapidly as voxel size increased. In contrast, within the artificially generated datasets, the clarity of cortical pores was better maintained until the largest voxel size (40 microm). Mean absolute percent error values, correlation coefficients, and paired t-tests revealed a pattern of increasing, and generally significant, differences between the smallest and progressively larger voxel sizes (both scanned and artificial). Relative to the actual scans, however, the artificial datasets were less sensitive to changing voxel size. These findings indicated that subtle changes in voxel size, within the range examined, have a considerable effect on human cortical porosity structural parameters. Additionally, the use of artificially increased voxel sizes should be viewed with caution as they may not reflect what can actually be obtained by scanning. PMID- 17340227 TI - Comparison of color LCD and medical-grade monochrome LCD displays in diagnostic radiology. AB - In diagnostic radiology, medical-grade monochrome displays are usually recommended because of their higher luminance. Standard color displays can be used as a less expensive alternative, but have a lower luminance. The aim of the present study was to compare image quality for these two types of displays. Images of a CDRAD contrast-detail phantom were read by four radiologists using a 2-megapixel (MP) color display (143 cd/m(2) maximum luminance) as well as 2-MP (295 cd/m(2)) and 3-MP monochrome displays. Thirty lumbar spine radiographs were also read by four radiologists using the color and the 2-MP monochrome display in a visual grading analysis (VGA). Very small differences were found between the displays when reading the CDRAD images. The VGA scores were -0.28 for the color and -0.25 for the monochrome display (p = 0.24; NS). It thus seems possible to use color displays in diagnostic radiology provided that grayscale adjustment is used. PMID- 17340228 TI - Validity and reliability of active shape models for the estimation of cobb angle in patients with adolescent idiopathic scoliosis. AB - Choosing the most suitable treatment for scoliosis relies heavily on accurate and reproducible Cobb angle measurement from successive radiographs. The objective is to reduce variability of Cobb angle measurement by reducing user intervention and bias. Custom software to increase automation of the Cobb angle measurement from posteroanterior radiographs was developed using active shape models. Validity and reliability of the automated system against a manual and semiautomated measurement method was conducted by two examiners each performing measurements on three occasions from a test set (N = 22). A training set (N = 47) of radiographs representative of curves seen in a scoliosis clinic was used to train the software to recognize vertebrae from T4 to L4. Images with a maximum Cobb angle between 20 degrees and 50 degrees , excluding surgical cases, were selected for training and test sets. Automated Cobb angles were calculated using best-fit slopes of the detected vertebrae endplates. Intraclass correlation coefficient (ICC) and standard error of measurement (SEM) showed high intraexaminer (ICC > 0.90, SEM 2 degrees -3 degrees ) and interexaminer (ICC > 0.82, SEM 2 degrees -4 degrees ), but poor intermethod reliability (ICC = 0.30, SEM 8 degrees -9 degrees ). The automated method underestimated large curves. The reliability improved (ICC = 0.70, SEM 4 degrees -5 degrees ) with exclusion of the four largest curves (>40 degrees ) in the test set. The automated method was reliable for moderate sized curves, and did detect vertebrae in larger curves with a modified training set of larger curves. PMID- 17340229 TI - Imaging non-dopaminergic function in Parkinson's disease. AB - In Parkinson's disease (PD), there is degeneration of the cholinergic, noradrenergic, and serotonergic systems in addition to dopaminergic projections. Function of these non-dopaminergic systems can be imaged with positron emission tomography (PET) and single photon emission computed tomography (SPECT) and correlated with motor and nonmotor symptomatology. In addition, neuronal loss in PD is associated with microglial activation. The role of microglia in driving the disease process remains uncertain. This review presents and discusses current findings in these areas. PMID- 17340231 TI - [Prevention of postoperative surgical wound infection: recommendations of the Hospital Hygiene and Infection Prevention Committee of the Robert Koch Institute]. PMID- 17340230 TI - [Relevant aspects of water hygiene]. PMID- 17340233 TI - Influence of valtrate/isovaltrate on the hematopoiesis and metabolic liver activity in mice in vivo. AB - Recently, cytotoxic effects of valepotriates with an epoxide moiety have been described on mouse bone marrow early progenitor cells IN VITRO. Consequently, the possible IN VIVO toxicity of valtrate on hematopoietic precursor cells was investigated. Mice were treated i.p. with 45 and 65 mg/kg or p.o. with 45 and 1350 mg/kg of the drug. Three days after treatment, colony formation of progenitor cells (CFC-S, GM-CFC, E-CFC) was not significantly different for control and experimental groups. Furthermore, the effect of valtrate on the ability of the liver to metabolize [ (14)C]methacetin was investigated by measuring the (14)CO (2) exhalation (breath test). There was a distinct reduction of the initial exhalation of (14)CO (2) following i.p. injection of 50 mg/kg of valtrate, but no effect was found after 50 or 1500 mg/kg of p.o. These results suggest that toxicity of valtrate in vivo is restricted because the distribution of the drug via circulation is obviously small. PMID- 17340234 TI - On the active agents of Valerian. AB - (13)C-NMR shifts of valepotriathydrines show a characteristic dependence on type and position of the acyloxy substituents. The structures of well known and of new valepotriathydrines have been clarified. PMID- 17340235 TI - HPLC analysis of valepotriates in the north american genera plectritis and valeriana. AB - Reversed phase HPLC has been applied to the isolation and quantitative distribution of valepotriates in roots and aerial parts of species and subspecies of the North American Genus PLECTRITIS (Valerianaceae) and in VALERIANA SITCHENSIS ssp. SCOULERI (Valerianaceae). A semipreparative Ultrasphere ODS column was used for separation and detection of small quantities of valepotriates in crude plant extracts. PMID- 17340236 TI - New Cleavage Methods for Cardiac Glycosides having a Doubly Linked Sugar1. AB - New cleavage methods for cardiac glycosides having a doubly linked sugar are described. Treatment with pyridine, alumina, or phenylhydrazine gave the desired genin in reasonable yield. The reaction products were separated and determined by high-performance liquid chromatography. The mechanism of the cleavage reaction has also been discussed. PMID- 17340237 TI - Biosynthesis of cardiac glycosides: Nucleotide-bound 2,6-dideoxy-3-O methylhexoses in leaf extracts of Nerium oleander. AB - From the leaves of NERIUM OLEANDER L. (Apocynaceae) nucleotide bound D-sarmentose and D-diginose were isolated and purified by use of PVP- and charcoal treatment and further separated by paper chromatography and electrophoresis. D-sarmentose and D-diginose werde identified by repeated thinlayer co-chromatography in two different solvent systems. Complete separation of L-oleandrose, D-cymarose, D sarmentose, D-diginose and D-digitoxose was achieved for the first time with one single TLC-system. PMID- 17340238 TI - Alkaloids from Thalictrum faberi. AB - Further phytochemical investigations of the roots of THALICTRUM FABERI Ulbr. led to the isolation and identification of four another additional bisbenzylisoquinoline alkaloids: O-methylthalibrine ( 1), thaligosine ( 2), O methylthalicberine ( 3), thalrugosidine ( 4), as well as pallidine ( 5). PMID- 17340239 TI - Identification of Alkaloids and Anthraquinones in Cinchona pubescens Callus Cultures; the Effect of Plant growth Regulators and Light on the Alkaloid Content. AB - Studies were performed on the alkaloid content of leaf and stem callus cultures of CINCHONA PUBESCENS Vahl with respect to the influence of plant growth regulators and light. The same alkaloids were found in the analysed tissues - with some quantitative differences. In general, a medium containing zeatin: 1 microM and 2,4-dichlorophenoxyacetic acid: 1 microM gave a higher alkaloid production than a medium containing benzyladenine: 8.1 microM and 2,4 dichlorophentoxy acetic acid: 4.5 microM. The alkaloid production in the unorganized callus cultures was stimulated by light. Anthraquinones were found in all tissue cultures. PMID- 17340240 TI - Studies on hernandiaceae VI. Lignans and alkaloids of Hernandia guianensis. AB - The lignoidic and alkaloidal content of the leaves, stem barks and root barks of H. GUIANENSIS has been studied; two aryltetrahydronaphthalenes, two dibenzylbutyrolactones and nine alkaloids are isolated. All components are identified by means of the spectral analysis. Eight alkaloids are aporphines and nor-aporphines. PMID- 17340241 TI - Alcaloides des Annonacees XLIX1: alcaloides d'Isolona hexaloba, I zenkeri et I. pilosa. AB - From ISOLONA HEXALOBA, I. ZENKERI and I. PILOSA, thirteen alkaloids have been isolated. Four of them are bisbenzylisoquinolines, the other ones are proaporphines or aporphines. Two aporphines, zenkerine, 9, and isopiline, 13, are new. Their structures have been established by examination of their spectral data and preparation of derivatives. PMID- 17340242 TI - Chemical Study of Alkaloids from Corydalis conspersa. AB - From the whole plant of CORYDALIS CONSPERSA, four benzo[ C]-phenanthridine-type alkaloids were isolated. Three of these were identified as corynoline, acetylcorynoline and corynoloxine. The fourth is a new alkaloid, named consperine. Its structure, C (26)H (27)NO (7), has been established to be 6 acetonylacetylcorynoline on the basis of spectral data and chemical synthesis. The configuration of acetonyl group in consperine is also discussed. PMID- 17340243 TI - The isolation of Nb-methyl-antirhine, malindine and isomalindine from Strychnos usambarensis. AB - Three quaternary alkaloids have been isolated from root barks of STRYCHNOS USAMBARENSIS Gilg from Rwanda: malindine, isomalindine and Nb-methyl-antirhine. The structure elucidation and the stereochemistry of the new isomalindine has been proposed based on its spectral data and their comparison with those of malindine, its isomer. PMID- 17340244 TI - Quantitative Determination of Forskolin by TLC and HPLC. AB - Thin layer chromatographic (TLC) and high pressure liquid chromatographic (HPLC) methods for quantitative determination of forskolin, a novel positive inotropic, antihypertensive, platelet aggregation inhibitory and adenylate cyclase stimulating agent are described. Both methods are suitable for the routine assay of pharmaceutical preparations containing forskolin. The HPLC method is also efficiently used for the assay of forskolin containing plant materials. A comparative evaluation is made of the two chromatographic methods with a previously reported gas liquid chromatographic method to determine forskolin. PMID- 17340245 TI - 6-O-Isobutyryl-tetrahydrohelenalin from the flowers of Arnica montana. AB - From the flowers of ARNICA MONTANA L., the helenanolides 6- O-isobutyryl tetrahydrohelenalin and 2beta-ethoxy-6- O-isobutyryl-2,3-dihydrohelenalin were isolated and their structures established by spectroscopic methods. PMID- 17340246 TI - New melampolides from Acanthospermum australe. AB - In addition to known compounds nine new melampolides have been isolated from the aerial parts of ACANTHOSPERMUM AUSTRALE. The structures were established by spectroscopic means and by comparing the spectral data with those of related compounds. PMID- 17340247 TI - Structures of Dianosides A and B, Analgesic Principles of Dianthus superbus var. longicalycinus Herbs1. AB - Novel triterpenoid saponins, dianosides A and B, showing analgesic activity, have been isolated from DIANTHUS SUPERBUS var. LONGICALYCINUS herbs. Degradative and spectroscopic studies have established their structures as shown in formulas 1 and 2. PMID- 17340248 TI - Structure of Dianosides C, D, E and F, Triterpenoid Saponins of Dianthus superbus var. longicalycinus Herb1. AB - On the basis of chemical and spectroscopic evidence, the structures of four triterpenoid saponins, dianosides C, D, E and F, from DIANTHUS SUPERBUS var. LONGICALYCINUS herb, have been elucidated as shown in formulas 1, 2, 3 and 4, respectively. PMID- 17340249 TI - An oxepane derivative of panaxadiol from the leaves of Panax notoginseng. AB - Hydrolysis of the crude saponin isolated from the leaves of PANAX NOTOGINSENG (Burk.) F. H. Chen yields five sapogenins which are separated by column chromatography. The structures of four of those were elucidated earlier to be panaxadiol, panaxatriol, dammar-20(22)en-3beta, 12beta,26-triol and 20(R) dammaran-3beta, 12beta,20,25-tetrol. The fifth sapogenin is identified as an oxepane derivative probably arising from acid catalyzed dehydration and rearrangement of panaxadiol. The structure as proposed from NMR data was confirmed by single-crystal X-ray diffractometry. PMID- 17340250 TI - XVIII: Eperudiendiol, Glycerides and Neolignans from Fruits of Osteophloeum platyspermum1. AB - The fruits of OSTEOPHLOEUM PLATYSPERMUM (Myristicaceae) contain sitosterol, eperu 8(20),13-dien-3alpha,15-diol, glyceryl laurodimyristate, glyceryl 1,3 lauromyristate and five neolignans: dihydroguaiaretic acid, hydroxyotobain, hydroxyoxootobain, guaiacin and otobaphenol. PMID- 17340251 TI - Composition of Essential Oil of Heracleum persicum Fruits. AB - The essential oil from fruits of HERACLEUM PERSICUM Desf., growing wild in Iran, was investigated by means of LSC, GLC and GC-MS. Co-chromatography of synthesized compounds was also applied for identification of components. The oil contained about 95% of aliphatic esters, 4% of aliphatic alcohols and 1% of monoterpenes; 37 esters and 17 monoterpenes were identified. PMID- 17340252 TI - The Effect of Water Stress on Growth and Solasodine Content in Solanum khasianum. AB - The effect of water stress on growth and development of SOLANUM KHASIANUM (Clarke) and on the solasodine content of its fruits, was studied under mild (field experiment) and severe (pot experiment) conditions. Under field conditions, vegetative development was inhibited but fruit production or yield were not affected and fruit maturity was enhanced considerably. Solasodine content was not affected and yield per plant remained the same with and without irrigation. Under conditions of severe water stress, fruit production and yield were affected as well as vegetative development. An increase in solasodine content per dry weight was observed, however, solasodine yield per plant was lower as a result of loss in fruit yield. Under conditions of extreme water stress, more negative water and osmotic potentials were developed and turgor was maintained in the leaves. PMID- 17340253 TI - Structure Activity Relations of Polyfunctional Diterpenes of the Tigliane Type, VI1. AB - A method for the isolation and preparation of 12-deoxyphorbol ( 1) from Euphorbium resin ( EUPHORBIA RESINIFERA Berg) was established to provide substantial amounts of 1-esters for bioassays. Acylation of 1 yielded 12 deoxyphorbol-13,20-diesters ( 2, esters with acids CH (3)(CH (2)) (n)COOH, n = 0, 4, 8, 12, 16, 20; and with benzoic, oleic, elaidic and linoleic acid). Upon mild transesterification the 13,20-diesters 2 yielded the 13-monoesters 3. Both ester types were tested for their irritant activities, the 13-monoesters were also assayed for their tumor-promoting activity. A dependance of both of these activities on the chain length of the acyl residues is noticeable. For both probably a broad maximum exists around the tetradecanoate. PMID- 17340254 TI - Studies on o-methylflavinantine. AB - The antinociceptive effects of O-methylflavinantine (OMF), a morphinandienone alkaloid, were investigated in the mouse hot plate and abdominal constriction tests (nociceptive agents: 5-Hydroxytryptamine, acetylcholine, bradykinin, prostaglandin, E (1) (PGE (1), formic acid and phenylquinone). The potency of OMF in the hot plate test was approximately 10 times less than that of morphine and the effect was naloxone reversible. In the abdominal constriction test, morphine was 78-650 times more potent than OMF, depending on the nociceptive agent used, but a higher dose of naloxone was necessary to reverse the response to formic acid. Pretreatment of mice with reserpine (1 mg/kg, s.c., 24 h) reduced and alpha methyl-p-tyrosine (200 mg/kg, i.p., 3 h) potentiated the antinociceptive effects of both morphine and OMF in the hot plate test. The results are considered to indicate that OMF possesses centrally mediated antinociceptive activity which is similar to that of morphine. PMID- 17340255 TI - Investigations of Molluscicidal Activity of Certain Sudanese Plants Used in Folk Medicine. Part IV*. AB - 50 plants indigenous to the Sudan and of common use in Sudanese folk-medicine, were screened for their molluscicidal activity, using two local snail vectors, BULINUS TRUNCATUS and BIOMPHALARIA PFEIFFERI. At different concentrations 31 (62%) of these plant samples were found to be lethal to either one or both of the snail species. 28 (56%) proved to be lethal to BIOMPHALARIA PFEIFFERI, 22 (44%) gave 100% mortality to BULINUS TRUNCATUS; while 19 (38%) killed both snail hosts (Table I). The seven most active molluscicidal plants were phytochemically screened for their active constituents; four of them showed the presence of saponins. PMID- 17340256 TI - Thyroid Stimulating Action of Z-Guggulsterone Obtained from Commiphora mukul. AB - A ketosteroid has been isolated from the oleo-resin of COMMIPHORA MUKUL and its structure (4,17(20)trans pregnandiene 3,16-dione; Z-guggulsterone) established from its physico-chemical properties, specially UV, IR, NMR and mass-spectra. The isolated ketosteroid showed a strong thyroid stimulatory action when administered to albino rats. Its administration (1 mg/100 g body weight) brought about an increase in iodine-uptake by thyroid and enhanced activities of thyroid peroxidase and protease as well as oxygen consumption by isolated slices of liver and biceps muscle. PMID- 17340257 TI - Antihepatotoxic Principles of Artemisia capillaris Buds1. AB - Since an extract of the crude drug "inchinko", the buds of ARTEMISIA CAPILLARIS, showed significant antihepatotoxic activity by means of carbon tetrachloride induced liver lesion IN VIVO and IN VITRO, the extract was fractionated by monitoring the activity to yield a number of flavonoids and a coumarin (6,7 dimethylesculetin). Antihepatotoxic effects of these constituents were determined by IN VITRO assay methods using carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes. Some analogues of dimethylesculetin were also assayed for liver-protective activity. Both the antihepatotoxic activity and the dimethylesculetin content in this plant were found to vary markedly with the date of harvesting, which was assumed to be a reason for remarkable variations of the antihepatotoxic activity in commercially available preparations of this crude drug. PMID- 17340258 TI - Tropane alkaloids of species of anthocercis, cyphanthera and crenidium. AB - Eight tropane alkaloids, anabasine and ursolic acid have been isolated from the newly-described species CRENIDIUM SPINESCENS. ANTHOCERCIS ILICIFOLIA possesses a similar alkaloid spectrum to that of A. LITTOREA to which it is taxonomically closely related. In alkaloid composition, A. GENISTOIDES is a variable species and the sample analysed here contained meteloidine as principal alkaloid. The alkaloids of CYPHANTHERA ODGERSII and C. TASMANICA are consistent with those of other species of the genus. At present, ursolic acid does not appear to be a useful characteristic for the classification of solanaceous taxa belonging to Anthocercideae. PMID- 17340259 TI - Quaternary Alkaloids of Tinospora capillipes. AB - Extracts of the roots of TINOSPORA CAPILLIPES Gagnep. (Menispertnaceae) afforded the quaternary protoberberine alkaloids palmatine, jatrorrhizine, columbamine, stepharanine and dehydrodiscretamine and the quaternary aporphine alkaloids menisperine and magnoflorine. PMID- 17340260 TI - An approach to the antiinflammatory activity of borjatriol. AB - The antiinflammatory activity of borjatriol (a diterpenoid isolated from SIDERITIS MUGRONENSIS Borja) was tested using the cotton pellet-granuloma assay. The compound inhibited the granuloma weight and the serum lysozyme activity in a dose-dependently way. The determination of this enzyme has allowed us to distinguish between an irritant (carrageenan) which reduces the granuloma weight and antiinflammatory substances (phenylbutazone and borjatriol). PMID- 17340261 TI - Strychnoxanthine, a monoterpene alkaloid of a novel skeletal type from Strychnos gossweileri. AB - Strychnoxanthine, an anhydronium base, was isolated from root barks of STRYCHNOS GOSSWEILERI, a few years ago. The structure of this new indole alkaloid is now established by spectral analysis, especially by (1)H NMR at 360 MHz. PMID- 17340262 TI - Constituents of Essential Oil of Nepeta nepetella. AB - The essential oil of NEPETA NEPETELLA L. growing in the Aosta Valley (Valnontey), Italy, obtained by steam distillation of the leaves and the flowers, was investigated by capillary gas chromatography in combination with mass spectrometry. To facilitate identification, fractionation of the oil with straight phase HPLC was performed. Nepetalactone (76.5%) is the main component of the oil. The isomers epinepetalactone (0.6%) and neonepetalactone (0.4%) together with the dihydro (1.6%) and dehydro (traces) nepetalactone derivatives were also identified. These compounds are considered to be responsible for the feline attractant activity of NEPETA NEPETELLA L. PMID- 17340263 TI - Studies on cryptolepine. AB - The inhibitory effects of cryptolepine and its interaction with prostaglandin E (2), indomethacin, adrenaline and acetylcholine have been investigated on the isolated rabbit duodenum. Cryptolepine (10-20 microg ml (-1)) or adrenaline (0.5 1 microg ml (-1)) or indomethacin (10-20 microg ml (-1)) abolished or reduced pendular contractions and relaxed the tissue. Cryptolepine (20 microg ml (-1)) produced an initial contraction before relaxation of the tissue. Cryptolepine (10 20 microg ml (-1)) abolished responses of the duodenum to added prostaglandin E (2) and acetylcholine, but failed to reduce prostaglandin production. The results suggested that cryptolepine antagonises prostaglandin, but has no inhibitory effect on its synthesis or release. PMID- 17340264 TI - Leaf Alkaloids of Zanthoxylum rubescens. AB - An alkaloid, 8-methoxy dictamnine ( 1) and a fagaramide like compound ( 2) were isolated from the leaves of ZANTHOXYLUM RUBESCENS for the first time. These compounds were absent in the root and stem barks from which nitidine chloride (0.013% (w)/ (w))( 3) and 9-methoxylchelerythrine (0.18% (w)/ (w))( 4) (possibly an artefact from chelerythrine) were isolated. PMID- 17340265 TI - 4-Methoxy-nor-Securinine, a New Alkaloid from Phyllanthus niruri. AB - From the aerial parts of PHYLLANTHUS NIRURI L. (Euphorbiaceae) plant two alkaloids 4-methoxy-securinine (phyllanthine) ( 1) and 4-methoxy-nor-securinine ( 2) have been isolated and their structures elucidated on the basis of spectroscopic data. The former alkaloid is isolated for the first time from this plant and the latter is a new alkaloid. PMID- 17340266 TI - (Z)-5-Hydroxy- and (Z)-4,5-dihydroxybutylidene-3-phthalides, new compounds isolated from Ligusticum wallichii. AB - Two new hydroxylated butylidenephthalides were extracted from LIGUSTICUM WALLICHII rhizom and their structures were assigned by spectral analysis. PMID- 17340267 TI - Methylated Flavonoids from Arnica montana and Arnica chamissonis. AB - From the flowers of ARNICA CHAMISSONIS Less, subsp. FOLIOSA var. INCANA, the methylated flavonoids acacetin, pectolinarigenin, hispidulin, jaceosidin, 6 methoxykaempferol, and betuletol have been isolated and identified by spectroscopic methods. Except for acacetin, the same flavonoids were identified in the flowers of ARNICA MONTANA L. Betuletol was found for the first time in the family of Asteraceae. PMID- 17340268 TI - Flavonoids in the leaves of Juniperus drupacea. AB - From leaves of JUNIPERUS DRUPACEA Amentoflavone, Cupressoflavone, Hinokiflavone, Quercitrin und Umbelliferone have been identified. PMID- 17340269 TI - Phthalides in Roots of Capnophyllum peregrinum and Peucedanum ostruthium. AB - In extracts from roots of CAPNOPHYLLUM PEREGRINUM Z-ligustilide was found to be present and in similar extracts of PEUCEDANUM OSTRUTHIUM cnidilide, Z-ligustilide and senkyunolide were detected. The compounds were analyzed by TLC, GLC and GCMS. PMID- 17340270 TI - Isolation and Characterization of the Major Anthraquinone Pigments from Rumex abysinica. AB - Emodin, chrysophanol and physcion have been shown to be the major anthraquinone pigments present in the dry roots of RUMEX ABYSINICA. PMID- 17340271 TI - Alkaloids and Coumarins from the Leaves of Amyris diatripa. AB - The alkaloids edulinine and (+/-) isoplatydesmine were isolated from the leaves of Amyris diatripa, being the first report of the presence of alkaloids in species of this genus. The presence of coumarins in the plant was also shown by isolation of psoralen, bergapten, marmesin, ulopterol and suberenol. PMID- 17340272 TI - A New Flavanonol Glycoside from Adansonia digitata Roots. AB - A new flavanonol glycoside isolated from the roots of Adansonia digitata has been characterised as 3,7-dihydroxy flavan-4-one-5-O-beta- D-galactopyranosyl (1 --> 4)-beta- D-glucopyranoside on the basis of degradation, spectral and chemical studies. PMID- 17340273 TI - Nor-Diterpene Oxides: Colensanone and Colensenone from Cassia petersiana. AB - The diterpenoids colensenone ( 1) and colensanone ( 2) have been isolated from the leaf extracts of Cassia petersiana Bolle. PMID- 17340274 TI - Sesquiterpene Lactones from Aegialophila pumila. AB - Cnicin was isolated as the major sesquiterpene lactone from Aegialophila pumila Jus. Boiss. The germacranolide salonitenolide was isolated as a minor constituent. Cnicin demonstrated pronounced cytotoxic activity when tested in vitro against TLX-5 mice lymphoma cells. PMID- 17340275 TI - Effect of guar gum on the gastric transit time in mice. PMID- 17340276 TI - Coumarins from "Zi-Hua Qian-Hu" (supplement). AB - Two new and six known coumarins were obtained from the Chinese drug sold in the market under the name of Si-Oian-Hu (Seizenko). The new compounds were proved to be 3'( S)-acetoxy-4'( R)-isovaleryloxy- and 3'( S)-acetoxy-4'( R)-angeloyloxy 3',4'-dihydroxanthyletin, respectively. Mass spectrometry was applied to determine the different locations of ester moieties at the 3' and 4' positions without using alkaline hydrolysis. The present material, Si-Qian-Hu, should be identified with Zi-Hua Qian-Hu (the root of PEUCEDANUM DECURSIVUM), since it contains xanthyletin-type coumarins. PMID- 17340277 TI - Chemistry of Acronycine VI. Proton NMR Spectral Assignments of Acronycine and Derivatives and the Formation of Isonoracronycine. AB - Proton NMR assignments for acronycine and a series of derivatives are reported based on extensive homonuclear decoupling and nOe experiments at high-field. The formation of isonoracronycine ( 3) from noracronycine ( 2) under acidic conditions is discussed. PMID- 17340278 TI - Components of root bark of morus lhou1 1. Structures of two new natural diels alder adducts, kuwanons N and o. AB - Kuwanons N and O, two new flavonoid derivatives with a fused dihydrochalcone partial moiety, and four known flavonoid derivatives, morusin, kuwanons G, H, and K, were isolated from the ethyl acetate extract of the root bark of MORUS LHOU (SER.) Koidz. The structures of kuwanons N and O were shown to be 1 and 2, respectively, on the basis of spectral data. They are regarded biogenetically as Diels-Alder adducts of a chalcone and a dehydroprenyl flavonoid. PMID- 17340279 TI - The isolation and structure elucidation of Afrocurarine. AB - The structure and the stereochemistry of afrocurarine (a new unsymmetrical bisindole alkaloid) previously isolated from S. USAMBARENSIS Gilg. are established especially from (1)H-NMR spectroscopic data. The separation of quaternary alkaloids has always been very tedious. Ion-pair reversed-phase column chromatography applied to the purification of afrocurarine is proved very useful and seems to be a suitable technique in quaternary alkaloid research. PMID- 17340280 TI - Minor Alkaloids of Corydalis bulbosa, Structure of Bulbodione. AB - As a result of the reinvestigation of the alkaloid content of CORYDALIS BULBOSA (L.) DC. (Papaveraceae), growing in Bulgaria, a new 8,11-dioxoaporphine alkaloid, named bulbodione, together with dihydrosanguinarine, dehydroglaucine, (+/-) sinactine, glaucinone and bicucullinine were isolated. These six alkaloids had not been detected in our initial study of the plant. The structure of buldodione was elucidated on the basis of spectral data and confirmed by synthesis of the alkaloid by means of Fremy's radical oxidation of bulbocapnine. The identification of the known alkaloids was obtained from their IR and (1)H-NMR spectral data and by direct comparison with authentic samples. PMID- 17340281 TI - Qualitative and quantitative isotachophoretic analysis of some quaternary isoquinoline alkaloids1,2. AB - A rapid isotachophoretic separation of benzo[ C]phenanthridine alkaloids from CHELIDONIUM MAJUS L. is described. The method allows the determination of sanguinarine and chelerythrine in the presence of other isoquinoline alkaloids in crude alkaloids extracts. PMID- 17340282 TI - The essential oil from Thymus praecox ssp. arcticus growing in Iceland. AB - The essential oil from THYMUS PRAECOX Opiz ssp. arcticus (E. Durand), Jalas, a widely distributed plant in Iceland, was proved to contain linalyl acetate as main component (70%). Within the sesquiterpene fraction, beta-caryophyllene (4%), germacrene D (3%), beta-bisabolene (2%), beta-sesquiphellandrene (1%), gamma cadinene (0.5%), and a couple of oxygenated sesquiterpenes (13%) were found by means of GLC-MS. Additionally four such compounds were isolated and identified by means of IR and NMR spectroscopy as nerolidol (3%), T-cadinol (1%), hedycaryol (7%), and 7-hydroxygermacrene (about 2%). PMID- 17340283 TI - Components of Root Bark of Cudrania tricuspidata 2. Structures of Two New Isoprenylated Flavones, Cudraflavones A and B. AB - Two new isoprenylated flavones, cudraflavones A and B were isolated from the root bark of CUDRANIA TRICUSPIDATA (Carr.) Bur. (Japanese name "Hariguwa", Moraceae). The structures of cudraflavones A and B were shown to be 1 and 2, respectively, on the basis of spectral data. Photo-oxidative cyclization occurred with cudraflavone B leading to the formation of a hydroperoxide possessing a dihydrooxepin ring. PMID- 17340285 TI - New Cardiac Glucosides from Digitalis lanata1. AB - From the leaves of DIGITALIS LANATA Ehrh. two as yet unknown cardenolides have been found. They were structurally elucidated as Digoxigenin-3-O-beta- D digitoxosido-beta- D-2,6-dideoxyglucoside and Digoxigenin-3-O-beta- D digitaloside by TLC and mainly spectroscopic methods. PMID- 17340284 TI - Part 1. Fractionation and biological properties of polysaccharides. AB - Water-soluble crude polysaccharide (AR-1) prepared from the root of ANGELICA ACUTILOBA Kitagawa (Japanese name = Yamato Tohki) was fractionated into three polysaccharide fractions, AR-2, AR-3 and AR-4 by the addition of cetyltrimethylammonium bromide. The major polysaccharide fraction, AR-2, consisted of a pectic acid-like molecule, and all fractions contained arabinose, galactose and glucose as the major neutral sugars. AR-4 showed the highest anti complementary activity and interferon inducing activity, but mitogenic activity was shown only in the AR-1. When AR-4 was further fractionated by anion-exchange chromatography, the anti-complementary and interferon inducing activities were observed in the different polysaccharide subfractions. These results indicate that both activities are caused by different polysaccharide molecules and that the mitogenic activity is due to a minor polysaccharide or other component rather than to the major polysaccharides. PMID- 17340286 TI - Decontamination of insecticides in natural drugs with supercritical carbon dioxide. AB - The lipophilic insecticides DDT and HCH in sennae leaves and pods are removable by extraction with supercritical carbon dioxide in the pressure region at 100 bar. The effective ingredients, the sennosides, are not extracted and remain in the drug of which they can be easily extracted with water. PMID- 17340287 TI - Weitere Phloroglucin- und alpha-Pyron-Derivate aus Helichrysum-Arten. AB - The investigation of three South African HELICHRYSUM species afforded a tremetone derivative, where the acetyl group is methylated, four phloroglucin derivatives, two of them being chromones, four alpha-pyrone derivatives and a dihydro chalcone also derived from phloroglucine. The structures were elucidated by sepectroscopic methods. PMID- 17340288 TI - Phenylethylamide aus Critoniella acuminata. PMID- 17340289 TI - Phytochemical Investigation of Hippeastrum vittatum. AB - The stereochemistry of pancracine, from HIPPEASTRUM VITTATUM, has been fully characterized as free base and as its O, O-di-acetate by means of spectroscopic analyses and CD-data. Carbon magnetic resonance data provide a simple tool in differentiating the contained montanine skeleton from other alkaloid ring systems within the Amaryllidaceae. PMID- 17340290 TI - Polyacetylenverbindungen aus Jungia seleriana. AB - The aerial parts of JUNGIA SETERIANA afforded in addition to known compounds two pairs of isomeric C (17)-acetylenes which differ in the number of triple bonds and in the configuration of the 9,10-double bond. The structures and configurations followed from the UV and the (1)H-NMR spectra, especially from those of the corresponding ketones, which were obtained by manganese dioxide oxidation. PMID- 17340291 TI - Sesquiterpenlactone aus berkheya-arten. AB - The aerial parts of BERKHEYA CARLINOPSIS ssp. MAGALISMONTANA afforded two new guaianolides closely related to subluteolide, while B. PAUCIFLORA gave desacetyl laurenobiolide and a costic acid derivative. The structures were elucidated by spectroscopic methods. PMID- 17340292 TI - Neue Guajanolide aus Centaurea imperialis. AB - The aerial parts of CENTAUREA IMPERIALIS afforded three new guaianolides, 3 desoxysolstitialin A and two derivatives of centaurepensin. PMID- 17340293 TI - Neue Aromadendren-Derivate aus Wyethia arizonica. AB - Die oberirdischen Teile von WYETHIA ARIZONICA enthalten neben bekannten Verbindungen zwei Aromadendren-Derivate, deren Strukturen durch eingehende spektroskopische Untersuchungen sowie durch Partialsynthese gesichert werden. PMID- 17340294 TI - 3beta-Hydroxy-lanosta-8,24-dien-21-al, a New Triterpene from Inontus obliquus. AB - A new triterpene, 3beta-hydroxy-lanosta-8,24-dien-21-al, was identified from INONOTUS OBLIQUUS. The structure was determined by IR, MS, (1)-NMR and (13)C-NMR spectroscopy and by comparing its (13)C-NMR spectra with the spectra obtained for lanosterol, inotodiol, trametenolic acid and methyl trametenolate. PMID- 17340295 TI - Nor-ent-labdan Derivate aus Austroeupatorium inulaefolium. AB - From the aerial parts of AUSTROEUPATORIUM INULAEFOLIUM three nor-ent-labdane derivatives were isolated, their structures and stereochemistry could be determined by high field NMR spectroscopy. PMID- 17340296 TI - 3-Propyl-8-Hydroxy-6-Methoxyisocumarin aus Solidago multiradiata. PMID- 17340297 TI - Germacranolide, Hydroxyverbenon und ent-Kaur-15(16)-en-17,19-disaure aus Helianthus occidentalis var. dowellianus. PMID- 17340298 TI - Pyrrolizidinalkaloide aus Senecio abrotanifolius, ssp. abrotanifolius und ssp. abrotanifolius, var. tiroliensis1. PMID- 17340299 TI - A Contribution to the Phytochemistry of Zanthoxylum tessmannii1. AB - Root bark extracts of ZANTHOXYLUM TESSMANNII (Engl.) Ayafor COMB. NOV. (Syn. FAGARA TESSMANNII Engl.) yielded, besides chelerythrine, dihydrochelerythrine, fagaramide and lupeol previously reported from this taxon, ten other compounds viz:nitidine, dihydronitidine, 9-methoxychelerthrine, gamma-fagarine, skimmianine, arctigenin methylether, savinin and a mixture of campesterol, beta sitosterol and stigmasterol. The implications of the present results for the taxonomic position of ZANTHOXYLUM TESSMANNII is discussed. PMID- 17340300 TI - Components of Root Bark of Cudrania tricuspidata l.1,2 Structures of Four New Isoprenylated Xanthones, Cudraxanthones A, B, C and D. AB - Four new isoprenylated xanthones, cudraxanthones A, B and C were isolated from the N-hexane extract of the root bark of CUDRANIA TRICUSPIDATA (Carr.) Bur. (Japanese name "Hariguwa"; Moraceae), and cudraxanthone D from the benzene extract. The structures of cudraxanthones A, B, C and D were shown to be 1-4, respectively, on the basis of spectral and chemical evidence. PMID- 17340301 TI - Salvianolic Acid A, a New Depside from Roots of Salvia miltiorrhiza. AB - A new depside of D-(+)-beta-(3,4-dihydroxyphenyl)-lactic acid and 2-(3,4 dihydroxyphenylethenyl)-caffeic acid, named salvianolic acid A, was isolated from the dried roots of SALVIA MILTIORRHIZA Bunge. Its chemical structure was defined by spectral analysis and chemical degradation. PMID- 17340302 TI - Radioimmunoassay for the quantitative determination of quinine in cultured plant tissues. AB - The development of a radioimmunossay for the determination of picogram amounts of quinine is described. The antiserum, raised against a conjugate of quinine and bovine serum albumin, is highly specific to the CINCHONA quinoline alkaloids having the 8S configuration and will not cross-react to any detectable extent with the 8R series. Neither will it cross-react with quininone or cinchonidinone, the common 9-keto precursors. Using this assay a number of clones of C. LEDGERIANA have been screened for their quinine content. PMID- 17340303 TI - Timing of Diosgenin Appearance in Suspension Cultures of Dioscorea deltoidea. AB - Cycloheximide and compactin were added to cell suspension cultures of DIOSCOREA DELTOIDEA. Cycloheximide inhibited growth and diosgenin biosynthesis completely at 40 mg/l when added during the growth phase. Compactin partially inhibited growth and diosgenin production at 100 microg/l when added during the growth phase. [1- (14)C]-Acetate incorporation into diosgenin was about 20-fold higher when added during the early stages of growth as compared to addition in the stationary phase. Incorporation of [1- (14)C]-acetate into diosgenin was inhibited by compactin only during the early stages of growth. These results indicate the formation of an accumulating intermediary metabolite during the early stages of growth which is transformed into diosgenin when D. DELTOIDEA cells are in the stationary phase. PMID- 17340304 TI - Indole Alkaloids from Catharanthus roseus Tissue Cultures IV1: 16R-19,20-E Isositsirikin, 16R-19,20-Z-Isositsirikin and 21-Hydroxycyclolochnerin. AB - From CATHARANTHUS ROSEUS cell suspension cultures 16 R-19,20- E-isositsirikine ( 1), 16 R-19,20- Z-isositsirikine ( 2) and a new sarpagine type indole alkaloid ( 5) have been isolated. The structures have been deduced from spectroscopic data; that of 5 has been confirmed by X-ray analysis. PMID- 17340305 TI - The Structure of New Valepotriates from Tissue Cultures of Valeriana wallichii. AB - Colchicin-treated tissue cultures of VALERIANA WALLICHII produced besides the known valepotriates homovaltrate, isovaltrate, valtrate, acevaltrate and didrovaltrate several unknown substances of diene-valepotriate structure. Nine genuine valepotriates and two degradation products were isolated and their structure elucidated by means of their (13)C-NMR spectra. PMID- 17340306 TI - Structures of Dianosides G, H and I, Triterpenoid Saponins of Dianthus superbus var. longicalycinus Herbs1. AB - Three novel triterpenoid saponins, dianosides G, H and I, together with the known saponin, azukisaponin IV, have been isolated from DIANTHUS SUPERBUS var. LONGICALYCINUS. The structures of the new saponins have been assigned as indicated in formulas 1,2 and 3, respectively, by spectral and chemical evidence. PMID- 17340307 TI - Cytotoxic Quassinoids from Odyendyea gabonensis Stem Bark: Isolation and High Field NMR. AB - The stem bark of ODYENDYEA GABONENSIS Engl. (Simaroubaceae) has yielded five quassinoids, identified as ailanthinone ( 1), 2'-acetoxyglaucarubinone ( 2), glaucarubinone ( 4), 2'-acetoxyglaucarubin ( 5) and excelsin ( 6), the simple coumarin scopoletin and the alkaloid 8-hydroxycanthin-6-one ( 3). Highfield (1)H- and (13)C-NMR spectra were recorded where possible and results are tabulated. PMID- 17340308 TI - Plant Anticancer Agents XXXIII. Constituents of Passerina vulgaris1. AB - Two lignans of known structure, (+)-syringaresinol, a cytotoxic agent, and (+) nortrachelogenin, a compound with demonstrated antileukemic activity, were isolated from a biologically active extract of the stems of PASSERINA VULGARIS. PMID- 17340309 TI - New Cardiac Glycosides from Digitalis lanata. AB - From the leaves of DIGITALIS LANATA Ehrh. two new Cardenolides have been found and structurally elucidated as Digoxigenin-3-O-beta- D-digitoxosido-beta- D digitoxosido-beta- D-2,6-dideoxy-glucoside and Glucodigoxoside by TLC and spectroscopic methods. PMID- 17340310 TI - New Cardiac Glycosides from Digitalis lanata. AB - From the leaves of DIGITALIS LANATA Ehrh. two new Cardenolides have been found and structurally elucidated as Digoxigenin-3-O-beta- D-digitoxosido-beta- D digitoxosido-beta- D-xyloside bei TLC and spectroscopic methods. PMID- 17340311 TI - IX, Natural Products from Vietnamese Plants. 20-Epi-kibataline, a New Steroidal Alkaloid from Paravallaris macrophylla. AB - The major constituent of the alkaloid fraction of leaves of PARAVALLARIS MACROPHYLLA Pierre was found to be the new paravallarine-type steroidal alkaloid, 20-epi-kibataline. The molecular and crystal structure of this steroidal alkaloid were determined by X-ray analysis. PMID- 17340312 TI - New Prenylflavanones and Chalcones from Helichrysum rugulosum. AB - Both the aerial parts and the roots of HELICHRYSUM RUGULOSUM afforded a complex mixture of prenylated flavanones and chalcones. The structures were elucidated by spectroscopic methods. PMID- 17340313 TI - N-Deformyl Vincristine a Bisalkaloid from Catharanthus roseus. AB - A bisalkaloid from CATHARANTHUS ROSEUS is N-deformyl vincristine (NDF). Its structure was clarified by spectroscopic methods. PMID- 17340314 TI - Isolation of a Guaianolide from Symphyopappus compressus. PMID- 17340315 TI - Psilocybin in Finnish Psilocybe semilanceata. AB - The use of a hallucinogenic mushroom, PSILOCYBE SEMILANCEATA, has been occasionally reported in Finland, where the species is widely distributed. We have determined, by HPLC, the content of psilocybin and psilocin in P. SEMILANCEATA samples collected from different parts of Finland; the psilocybin content was found to be high (0.62-2.37%, mean 1.42% of dry weight), some samples also contained low concentrations (0.01-0.02% dry weight) of psilocin. PMID- 17340316 TI - Naphthoquinones of Diospyros usambarensis; their Molluscicidal and Fungicidal Activities1. AB - The molluscicidal and fungicidal properties of DIOSPYROS USAMBARENSIS root bark have been attributed to the naphthoquinone 7-methyljuglone. In addition, the dimeric naphthoquinones isodiospyrin and mamegakinone and 2 artefacts, 2-methoxy- and 3-methoxy-7-methyljuglone have been isolated. PMID- 17340317 TI - Major Alkaloid and Flavonoid of Premna integrifolia. PMID- 17340319 TI - Tetrahydroalstonine from Fruits of Rhazya stricta. AB - An indole alkaloid isolated from the fruits of RHAZYA STRICTA Dec., has been identified as tetrahydroalstonine on the basis of spectroscopic studies and by comparison with the authentic sample. PMID- 17340318 TI - Bis-1-Benzyltetrahydroisoquinoline Alkaloids from Cleistopholis staudtii1. PMID- 17340320 TI - Erratum. PMID- 17340321 TI - A Further Guaianolide from Kaunia arbuscularis. PMID- 17340322 TI - Alkaloids from Roots of Strempeliopsis strempelioides - Structures of Strempeliopine and Strempeliopidine1. AB - From the roots of STREMPELIOPSIS STREMPELIOIDES K. Schum. (Apocynaceae), the following alkaloids were isolated: (+)-pleiocarpamine, (-)-aspidospermine, (+) eburnamonine, (+)-tubotaiwine, (+)-haplocidine, (-)-vallesamidine, (+) tubotaiwine N-oxide, (-)-strempeliopine ( 1A) and a bisindolic base (+) strempeliopidine ( 2). Another bisindole alkaloid of composition C (38)H (46)N (4) was isolated in minute quantity. The structures were established on the basis of spectral and chemical evidence. PMID- 17340323 TI - Comparative Study on the Production and Accumulation of Essential Oil in the whole Plant and in the Callus Culture of Matricaria chamomilla. AB - Localisation, accumulation and composition of the essential oil in different plant parts of MATRICARIA CHAMOMILLA L. were investigated. An organ specific distribution of individual components in the different essential oils could be shown. Only the essential oil of the roots contained the sesquiterpenes Chamomillol, Caryophyllen, Caryophyllenepoxide and the polyenes Chamomillaester I and II. The essential oil of MATRICARIA CHAMOMILLA roots is accumulated in schizogenous oil passages and oil cells restricted to the roots. Callus surface cultures of MATRICARIA CHAMOMILLA initiated from stems and flowerheads produced an essential oil similar to that of the root. It is exclusively accumulated in oil cells typical of the roots. PMID- 17340324 TI - Intracellular Localization and Secretion of Naphthoquinone Pigments in Cell Cultures of Lithospermum erythrorhizon. AB - The intracellular localization and secretion process of naphthoquinone pigments (shikonin derivatives) in cell cultures of LITHOSPERMUM ERYTHRORHIZON were investigated chiefly by electron microscopy. The results have suggested that the pigments accumulate in "secretion vesicles" which originate from electron dense, spherical swellings formed in highly elongated, rough endoplasmic reticula. Most of these vesicles appeared to fuse with the plasma membrane to secrete the contents consisting mainly of shikonin pigments, lipids, and proteins to the outside of the cell wall. PMID- 17340325 TI - Detection of psilocybin and psilocin in norwegian species of pluteus and conocybe. AB - A screening of Norwegian mushrooms for the presence of hallucinogenic indole alkaloids was carried out using HPLC with ultraviolet, fluorescence and electrochemical detection. The analysis revealed psilocybin and psilocin in two mushroom species: PLUTEUS SALICINUS and CONOCYBE CYANOPUS. The content of psilocybin and psilocin in dried material of PLUTEUS SALICINUS was determined to be 0.35% and 0.011%, respectively, and dried samples of CONOCYBE CYANOPUS were found to contain 0.33-0.55% psilocybin and 0.004-0.007% psilocin. PMID- 17340326 TI - Panax ginseng: Relation between Age of Plant and Content of Ginsenosides. AB - The roots of PANAX GINSENG C. A. Meyer contain a relatively high percentage of ginsenosides from their first year of life onwards. Since the major development of weight of roots occurs between the 4th and 5th year of life, it has been established that the highest yield of ginsenosides and therefore the best time for harvesting the roots is at the end of the summer of the 5th year. PMID- 17340327 TI - Gynocardin from passiflora. AB - Gynocardin has been isolated and identified for the first time from a species of PASSIFLORA. This compound is typical of the FLACOURTIACEAE, and its presence in the PASSIFLORACEAE underscores the close relationship of the two families. PMID- 17340328 TI - Evaluation of antiinflammatory activity of a chamomile extract after topical application. PMID- 17340329 TI - Flavonoid Aglycones in some Digitalis Species. PMID- 17340330 TI - Flavonoids from Mentha piperita Leaves. PMID- 17340331 TI - Senecionine from Gynura segetum. PMID- 17340333 TI - Editorial. PMID- 17340332 TI - New Guaianolides from Centaurea kandavanensis. PMID- 17340334 TI - The systematic distribution of ferulic Acid-sucrose esters in anthers of the liliaceae1. AB - In an anther survey of 157 di- and monocotyledons, two very rare cinnamic acid conjugates-di- and triferuloylsucrose-were found to occur exclusively in the Liliales and most predominantly in the Liliaceae (Tulipeae, Lilieae, Lloydieae). Whereas the triferuloyl ester was found to be abundant in most of the 20 species and cultivars of TULIPA investigated, only the diferuloyl ester could be detected by the applied methods in FRITILLARIA and LILIUM, in 12 and 9 species and cultivars, respectively. Di- and/or triferuloylsucrose could also be detected in one GAGEA and three ERYTHRONIUM species. Three out of 20 IRIS species investigated, also show the occurrence of these rare esters. This sporadic appearance in IRIS is, at present, considered to be erratic. We suggest that the ferulic acid-sucrose esters might be useful as marker substances for the Liliaceae. PMID- 17340335 TI - Chemosystematics of the gnetatae and the chemical evolution of seed plants1. AB - A survey of the secondary metabolites reported for EPHEDRA, WELWITSCHIA and GNETUM documents a far-reaching chemical similarity of these genera with the angiosperms. However, the different substitution patterns of the phenolics do not support a close phylogenetic link between the two groups. The most significant chemical difference between the Gnetatae and the angiosperms seems to be the widespread use of protective devices against oxidation such as O-methylation and formation of Schiff bases which are so frequent in angiosperms and nearly absent from the Gnetatae and other gymnosperms. PMID- 17340336 TI - Composition of Essential Oil of Ocimum kilimandscharicum Grown in Rwanda1. AB - The essential oil of OCIMUM KILIMANDSCHARICUM Guerke, growing wild in Rwanda, was investigated by LSC, GLC and GC-MS. The oil contained 62% 1.8-cineole, indicating the occurrence of a new chemotype of the species concerned. In addition to 1.8 cineole, 16 oxygen-containing compounds and 14 monoterpene hydrocarbons were identified, of which limonene and beta-pinene were the main components. Most of the constituents were not previously known to be present in the essential oil of O. KILIMANDSCHARICUM. PMID- 17340337 TI - Cyanogenic Glycosides from Triticum monococcum. AB - The cyanogenic glucosides obtained from etiolated seedlings of TRITICUM MONOCOCCUN var. HORNEMANII have been identified by chromatographic and spectroscopic techniques as linamarin, lotaustrahn and epilotaustralin. PMID- 17340338 TI - Structure of Triterpene-Sapogenins of Aesculus glabra1. AB - After extraction of coarsely ground seeds of AESCULUS GLABRA Willd. with 80% methanol the saponin fraction was submitted to enzymatic and acid hydrolysis, giving qualitatively identical TLC-spectra of the sapogenins. For separation of the obtained sapogenins silica gel-columns with chloroform-methanol-water mixtures as mobile phases were employed. Five main components (genins G-A to G E), identified as 21,22-diangeloyl-barringtogenol C, 21,22-diangeloyl-R (1) barrigenol, 21-angeloyl-barringtogenol C, 22-angeloyl-R (1)-barrigenol and 21 angeloyl-R (1) barrigenol have been isolated. Structure elucidation was accomplished by (1)H-NMR and mass spectrometry of the genins, their acetates and several isopropyliden derivatives. The acid free sapogenins barringtogenol C and R (1) barrigenol (G-F and G-G) were found and identified by thin layer chromatography. PMID- 17340339 TI - Aspects on the Biosynthesis of the Cyanogenic Glucoside Triglochinin in Triglochin maritima1. AB - The incorporation of L-[U- (14)C]phenylalanine, L-[U- (14)C]tyrosine and [U- (14)C]4-hydroxyphenylacetonitrile into triglochinin and taxiphyllin, the latter a possible precursor of the former, was studied in seedlings of TRIGLOCHIN MARITIMA L. The nitrile was by far the best substrate; incorporation of the amino acids was poor. Environmental factors such as light and humidity act differently on production of both compounds which also show a wide variation in individual seedlings. Quantitative evaluation of the specific activities indicate that taxiphyllin cannot be regarded as a precursor of triglochinin and that the two compounds are probably synthesized by two, at least mainly independent, pathways. PMID- 17340340 TI - Desorption/Chemical ionization mass spectrometry of bitter glycosides from gentiana1. AB - A series of bitter secoiridoid glucosides isolated from various GENTIANA species (Gentianaceae) have been investigated by D/CI-MS. Amarogentin, amaropanin, amaroswerin, deglucosyltrifloroside, desacetylcentapicrin, gentiopicrin, swertiamarin and sweroside have been characterized by quasimolecular ions and typical fragments, using NH (3) or CH (4) as reactant gas. PMID- 17340341 TI - Modern HPLC as a Tool for Chemotaxonomical Investigations: Iridoid Glucosides and Acetylated Flavonoids in the Group of Stachys recta1. AB - In the present study, modern RP-HPLC is applied for chemotaxonomical investigations of ten species of the group of STACHYS RECTA (Labiatae) and three closely related species. Precise quantitative data of five iridoids and eight flavonoids are obtained for a total of fifty different origins. The handling of the numerous samples for analysis was facilitated by an automatic injection system. By application of diode array technology, each peak could be characterized, supplementary to its retention time, by its UV data. Except for three Yugoslavian specimens of S. RECTA, all investigated origins could be classified by their iridoid and flavonoid contents. The differences are mainly of a quantitative nature. The separation of S. ANGUSTIFOLIA from the S. RECTA group, postulated by Koeva-Todorovska by means of pollen morphological and cytological characters, is confirmed by the presented chemotaxonomical data. PMID- 17340342 TI - Studies on the Chemical Constituents of Kadsura longipedunculata: Isolation and Structure Elucidation of Five New Lignans. AB - Five new dibenzocyclooctadiene lignans, R(+)-wuweizisu C ( 1), kadsuranin ( 2), R(+)-gomisin M (1) ( 3), R(+)-angeloylgomisin M (1) ( 4) and angeloylgomisin R ( 5) were isolated from the ethereal extract of roots and stems of KADSURA LONGIPEDUNCULATA Finet et Gagnep. Their structures were elucidated on the basis of chemical and spectral analysis. PMID- 17340343 TI - Serruloside and Serrulatoside, two New Iridoid Glycosides from Penstemon serrulatus1. AB - From leaves of PENSTEMON SERRULATUS Menz. two new iridoid glycosides have been isolated. Both glycosides have the same aglycon part, but differ in their carbohydrate moieties. The structure of serru-loside (penstemidaglucon-11- O-beta D-ribohexos -3-uloside) and serrulatoside (penstemidaglucon-ll- O-beta-4' desoxyaltropyranosido-6'- O-beta- D-glucopyranoside) was established by spectroscopic methods (mainly (1)H- and (13)C-NMR) and comparison with known compounds. PMID- 17340344 TI - Alkaloidal Constituents of Crinum bulbispermum III: Bulbispermine, a New Alkaloid of Crinum bulbispermum1. AB - The structure, relative and absolute configuration of bulbispermine from CRINUM BULBISPERMUM (Amaryllidaceae) is elucidated with spectroscopic techniques and via its methiodide, UV, CD, IR, MS, (1)H- and (13)C-NMR data, [alpha] (20)(D). PMID- 17340345 TI - Instability of Indole Alkaloid Production in Catharanthus roseus Cell Suspension Cultures. AB - Using serpentine fluorescence as an indicator of alkaloid production in cultured CATHARANTHUS ROSEUS cells, 6 cell lines producing alkaloid in excess of 300 mg/l were selected from more than 2 x 10 (5) individual colonies and their alkaloid production was monitored over a period of 8 years. Rapid loss of productivity invariably occurred during the first few months of cultivation, and spontaneous recovery of the initial production rates was never observed. Production of the indole alkaloid precursor, secologanin, followed the same pattern. Recovery of high alkaloid yielding strains was, however, possible at any time by repetition of the clonal selection procedure, but these strains were again instable. Clonal selection of high yielding plant cell strains apparently favours an inherent instability. PMID- 17340346 TI - Serrulatoloside, a New Iridoid Glucoside from Penstemon serrulatus. AB - From leaves of PENSTEMON SERRULATUS Menz. a new iridoid glucoside of unusual type in having an exo double bond at C-8 on the cyclopentane-ring has been isolated. The structure of serrulatoloside has been established by spectroscopic methods. PMID- 17340347 TI - Hemlock Alkaloids in Aloes. Occurrence and Distribution of gamma-Coniceine. AB - The hemlock alkaloid gamma-coniceine was identified in a number of ALOE species, namely A. GILLILANDII, Reynolds A. BALLYI Reynolds, A. RUSPOLIANA Baker, A. IBITIENSIS Perrier and A. DELTOIDEODONTA Baker. Coniine was identified in A. VIGUIERI Perrier. The levels of gamma-coniceine are higher than those found in CONIUM MACULATUM L. Some species also contained trace amounts of conhydrinone and pseudoconhydrin. Three of the species are Madagascan endemics, one is restricted to Arabia, while the rest are remote from each other in East Africa. Some of the species are loosely related but there is no overall taxonomic affinity between them. PMID- 17340348 TI - Iridoid Glucosides and an Acetophenone Glucoside from Penstemon whippleanus. AB - From leaves of PENSTEMON WHIPPLEANUS A. Gray three iridoid glucosides and an acetophenone glucoside have been isolated which were proved to be 10- T cinnamoylaucubin, eurostoside, mussaenoside and picein, respectively. PMID- 17340349 TI - 12-Hydroxy-ll-methoxy-diaboline: A New Alkaloid from Strychnos spinosa. AB - From the stem bark of STRYCHNOS SPINOSA two tertiary alkaloids were isolated. By means of their spectral data they were identified as 11-methoxy-diaboline and 12 hy-droxy-11-methoxy-diaboline. PMID- 17340350 TI - Dodonic Acid, A New Diterpenoid from Dodonaea viscosa1. AB - The aerial parts of DODONAEA VISCOSA afforded a new diterpenoid, dodonic acid, the structure and stereochemistry of which have been established by chemical and spectroscopic means. PMID- 17340351 TI - Anthraquinones, Anthrones and Dianthrones in Callus Cultures of Rhamnus frangula and Rhamnus purshiana. AB - Tissue cultures initiated from the cambial zone in branches of RHAMNUS FRANGULA L. and RHAMNUS PURSHIANA DC were grown on modified Murashige and Skoog medium with kinetin and 2,4-D as growth factors. To study the production of the genuine anthraquinone derivatives, the extraction of the fresh calli was performed in such a way that oxidation was prevented. In the fresh callus of RHAMNUS FRANGULA the glycosides of chrysophanoldianthrone and chrysophanolphys-ciondianthrone predominantly occurred, whereas in the freeze dried bark of RHAMNUS FRANGULA the glycosides of emodin and emodinanthrone were the main components. Aloe-emodin, which does not occur in the intact bark material of RHAMNUS FRANGULA, was proved to be present in the callus culture. In the fresh callus of RHAMNUS PURSHIANA the glycosides of chrysophanolanthrone and physcionanthrone dominated, while in the freeze dried bark of RHAMNUS PURSHIANA the glycosides of emodin, emodinanthrone and aloe-emodin were predominantly present. The total yields of the glycosidic bound aglycones produced in both cultures were approximately one third of the yields produced in the bark of the two intact species from which the cultures originated. PMID- 17340352 TI - Sesquiterpene Lactones in Leaves of Jurinea albicaulis. AB - Two new germacranolides 8alpha-tiglylalbicolide, 4, and juricanolide, 5, as well as the known albicolide, 1, junneolide, 2, and pectorolide, 3, and the coumarin scopoletin, were found in the leaves overground part of J. ALBICAULIS L. collected from the South Bulgarian Black-Sea costal sands. PMID- 17340353 TI - Variability in Alkaloid Content of Discaria pubescens. PMID- 17340354 TI - Alkaloids of Monodora tenuifolia. PMID- 17340355 TI - Microbiological C-17-oxidation of clavine alkaloids. PMID- 17340356 TI - Dolichantoside, Main Alkaloid from Stem Bark of Strychnos tricalysioides. PMID- 17340358 TI - Alkaloids of Nauclea officinalis. AB - Five minor alkaloids were isolated from the stems of NAUCLEA OFFICINALIS Pierre ex Pitard: three new alkaloids named naucleficine ( 1), nauclefidine ( 2) and nauclefoline ( 3), and two known alkaloids 1-acetyl-beta-carboline and naucleidinal, along with vanillic acid. PMID- 17340357 TI - The Compounds of Valeriana alliariifolia. PMID- 17340359 TI - Alkaloids of Fumaria indica: Further Studies on Narceimine and Narlumidine. AB - The structures of the FUMARIA INDICA alkaloids narceimine and narlumidine, earlier proposed by us, have been substantiated by further chemical reactions and characterisation of chemical transformation products. Isolation and characterisation of two naturally occurring alkaloid salts, protopine nitrate and tetrahydrocoptisine hydrochloride, along with (+)-adlumidine, norsanguinarine and an uncharacterised alkaloid, C (20)H (17)NO (6) (M (+) 367), mp 250-251 degrees C, from the same plant are also reported. PMID- 17340360 TI - A New Iridoid Glucoside of Swertia japonica. AB - The structure of swertiaside, a new iridoid glucoside isolated from SWERTIA JAPONICA, was elucidated to be 7-epi-( M-hydroxybenzoyl)-loganicacid. PMID- 17340361 TI - Studies on Coumarins of a Chinese Drug "Qian-Hu" V. Coumarin-glycosides from "Zi Hua Qian-Hu"1. AB - Decuroside V [3' ( R)-hydroxy-nodakenin-3'-ol] and decuroside IV [nodakenetin 4'- O-beta- D-apiofuranosyl (1-->6)beta-D-glucopyranolsyl], two new coumarin glycosides, were isolated from a Chinese drug sold under the name of Si-Qian-Hu (Seizenko) and Kwan-Si Qian-Hu (Koseizenko), the roots of PEUCEDANUM DECURSIVUM Maxim. (Umbelliferae). The structures were determined by means of spectroscopic analysis and chemical reactions. (1)H-NMR spectra showed the beta-configuration of the all sugar linkages. PMID- 17340362 TI - Studies on Coumarins of a Chinese Drug "Qian-Hu"; VI1, Coumarins of Angelica edulis. AB - Coumarins, edulisin I (Ae-I) ( 1) and edulisin II (Ae-VI) ( 6), were isolated from ether extracts of the roots and rhizomes of ANGELICA EDULIS Miyabe (Umbelliferae), together with five known coumarins. The structures of edulisin I ( 1) and edulisin II ( 6) were established to be 2' ( S), 3' ( R)-3'-senesioyloxy O-trans-p-coumaroyl-2', 3'-dihydrooroselol and 2' ( S), 3' ( R)-senecioyloxy- O- senecioyl-2', 3'-dihydro-oroselol by chemical studies and spectral analysis. Ae III ( 3) was identified with isopeucenidin and the configuration at C-2' and C-3' of Ae-III ( 3) was assigned as R and R, respectively by chemical studies and an X ray crystallographic analysis. Accordingly, the optical rotation of isopeucenidin reported by Steck and Wetter has been corrected. PMID- 17340363 TI - Influence of Sucrose on Levels of Ajmalicine, Serpentine, and Tryptamine in Catharanthus roseus Cells in vitro. AB - The fates of major nutritional elements and the synthesis of tryptophan, tryptamine and 2 alkaloid markers in C. ROSEUS cells, cultivated in media containing 20 and 60 g/l of sucrose, were studied. Sucrose effects were greatest, with these parameters, during the stationary growth phase. Intracellular ajmalicine and serpentine levels increased with sucrose concentration, whereas intracellular tryptamine (nitrogen precursor) levels were unaffected. The role of sucrose in the alkaloid pathway is discussed. PMID- 17340364 TI - Homonataloin in Aloe species. AB - Homonataloin levels in exudates from cut leaves of a number of ALOE species from the Kew collection have been measured by absorption at 295 nm following separation by reversed phase HPLC. The level was found to be highest in the leaves just below the apex of the plant and to decrease in the older leaves. A range of concentrations was observed in the very variable species A. NYERIENSIS Christian but no taxonomically significant discontinuities were apparent. Other ALOE species containing homonataloin have been examined and levels from 14 per cent to 47 per cent of the exudate dry weight according to species were found. PMID- 17340365 TI - Elicitor-Induced Accumulation of Acridone Alkaloid Epoxides in Ruta graveolens Suspension Cultures. AB - Light and dark grown suspension cultures of RUTA GRAVEOLENS produced small amounts (1-50 microg/g dry weight) of the antimicrobial alkaloids rutacridone epoxide and hydroxyrutacridone epoxide. Acrid-one epoxide accumulation could be increased up to a 100 fold within 72 h by elicitation through addition of a suspension of either living free or immobilized yeasts, of dead RHODOTORULA RUBRA cells or crude cell wall fraction. Chitosan and alginate, exhibiting elicitor properties in other systems, scarcely had an effect, arachidonic acid and elaidic acid were ineffective. The elicitors of acridone epoxide accumulation did not effect an increase of rutacridone in RUTA cultures. PMID- 17340366 TI - Plant Antiviral Agents; VI.1 3-Methoxyflavones as Potent Inhibitors of Viral Induced Block of Cell Synthesis. AB - An investigation of the constituents responsible for the pronounced antiviral activity observed for extracts of EUPHORBIA GRANTII Oliv. stems has afforded four related 3-methoxyflavones exhibiting remarkable activities against picornaviruses and vesicular stomatitis virus. All compounds were found to be derivatives of 3 methylquercetin. The concentration of 3-methylquercetin (3-MQ) and 3,3'-dimethyl quercetin (3,3'-DMQ) inhibiting 90 % of polio type 1 and coxsackie B4 viruses in tissue culture was about 0.01 microg/ml, whereas the 50 % cytotoxic concentration was 40 microg/ml. When administered intraperitoneally, 3-MQ protected mice from viremia and lethal infections from coxsac kie B4 virus at a daily dose of 20 mg/kg for a period of nine days. Biochemical studies on the mechanism of action of 3-MQ or 3,3'-DMQ on poliovirus replication suggested that these 3 methoxyflavones are able to protect the host cells from a viral induced shutdown of the cellular protein synthesis. Preliminary structure activity relationship studies have shown the 3-methoxyfunction of the flavones to be essential for the observed antiviral effects. PMID- 17340367 TI - Monechmol, a New Pentacyclic Triterpene from Monechma debile. AB - Monechmol, a new hydroxypenta-cyclic triterpene, has been isolated from MONECHMA DEBILE Hochst. The butanol fraction has afforded a glucoside which was characterized as monechmol 3-O-beta-glucoside. PMID- 17340368 TI - Alkaloids from Esenbeckia pilocarpoides. AB - A preliminary screening showed the occurrence of alkaloids only in root bark and roots of ESENBECKIA PILOCARPOIDES H. B. K., (Rutaceae). Six alkaloids have been isolated and identified from root bark: one acridone, 1-hydroxy-3-methoxy- N methyl-acridone; four furoquinolines, maculine, flindersiamine, kokusaginine, kokusagine; the sixth, isomaculine, a furo-4-quinolone, known as a synthetic product, has been isolated for the first time from a natural source. PMID- 17340369 TI - Aloe-Emodin Acetate, an Anthraquinone Derivative from Leaves of Kniphofia foliosa. AB - The leaves of K. FOLIOSA yielded aloe-emodin acetate in addition to chrysophanol and knipholone. Aloe-emodin acetate is reported here in Liliaceae family for the first time. PMID- 17340370 TI - Triterpenoids and Flavonoids of Vitex peduncularis. PMID- 17340371 TI - Ishwarol, the main Sesquiterpene in Piper amalago. PMID- 17340372 TI - Separation of cardanols by reversed phase HPLC. PMID- 17340373 TI - Further iridoids from penstemon species. PMID- 17340375 TI - Polyphenolic Molluscicides from Acacia nilotica. PMID- 17340374 TI - Merucathine, A New Phenylalkylamine from Catha edulis. PMID- 17340376 TI - Continuing education self-study program. PMID- 17340378 TI - Curriculum-based emergent literacy assessment in early childhood. AB - Speech-language pathologists who work in early childhood settings are concerned with monitoring and evaluating progress and making appropriate instructional adjustments to promote at-risk children's language and literacy development. Curriculum-based assessment can be effective in providing practitioners with this type of information. This article discusses processes and procedures for implementing curriculum-based assessment and suggests methods that professionals can use to teach assessment tasks to children who struggle with the task demands. PMID- 17340379 TI - Targets, techniques, and treatment contexts in emergent literacy intervention. AB - This article provides an overview of three important considerations when delivering evidence-based emergent literacy interventions: (1) treatment targets, (2) treatment techniques, and (3) treatment contexts. Treatment targets refer to the specific aspects of emergent literacy that clinicians address within their interventions and are organized into two broad areas: code-related skills and meaning-related skills. Specific targets within each skill area are identified. Treatment techniques refer to the specific clinical approaches used to address these targets. Using the scaffolding metaphor, we differentiate between use of high-support and low-support techniques for moving children along a continuum from dependence to independence. Treatment contexts refer to the location in which intervention is provided; prevalent contexts for provision of emergent literacy intervention include classroom-based, pull-out, and home-based (parent implemented) interventions. PMID- 17340380 TI - Optimizing literacy in English language learners. AB - Children in the United States who are English language learners characteristically do not exhibit the same levels of reading achievement as their peers. The article describes the development of English literacy in English language learners and the relationship between a child's second language (L2) and his or her native language (L1) in literacy development. It is organized first to consider the issue of language of instruction and language transfer, specifically the aspects of L1 literacy that appear to transfer to the second language (L2), English. It then discusses general principles for professionals working to optimize English literacy development in different models of literacy instruction for English language learners. We conclude that using the child's L1 provides the children with strong language and literacy skills in both languages. PMID- 17340381 TI - Literacy and children with specific language impairment. AB - The purpose of this article is to summarize the literacy outcomes for children with specific language impairment and to consider principles and approaches for literacy intervention with preschool and early school-age children with language impairments. Initially, specific language impairment is defined and differentiated from nonspecific language impairment. In addressing intervention considerations, we first consider the application of best practice principles and then specifically focus on intervention with preschool children and intervention with early school-age children. Consideration of evidence-based treatment approaches is guided by the developmental literature and by the intervention literature. PMID- 17340382 TI - Childhood apraxia of speech: children at risk for persistent reading and spelling disorder. AB - This article discusses written language development in children with childhood apraxia of speech (CAS). Children with CAS are at risk for persistent reading and spelling disorder in addition to their spoken communication difficulties. The article highlights four factors that increase the risk of written language disorder in this population: (1) the nature of the speech disorder, (2) the presence of phonological awareness difficulties, (3) genetic risk factors, and (4) the negative impact of early reading difficulty on later written language development. The article suggests that traditional approaches used to target articulation in CAS may do little to develop skills that are critical to early literacy acquisition and stresses the importance of integrating speech, phonological awareness, and literacy goals for this population. Data presented from a pilot intervention study with three children with CAS aged 6 and 7 years highlight the potential benefit of an integrated phonological awareness approach to improve simultaneously speech, phonological awareness, and decoding ability. The need for further empirical evaluation of treatment approaches designed to improve the spoken and written language outcomes of children with CAS is emphasized. PMID- 17340383 TI - Literacy and visual impairment. AB - Research supporting specific instructional approaches for young children with visual impairments and blindness is limited. There is, however, a growing body of evidence to support the belief that the critical components of emergent and early conventional literacy for children with visual impairments do not differ markedly from those of their sighted peers. Specifically, infants and toddlers with visual impairments and blindness require interactions that support their oral language development, awareness of print or braille, and opportunities to explore writing. Although these very young children are often delayed in developing emergent literacy understandings, the path of their development is consistent with emergent literacy development of sighted children. The research regarding older children with visual impairments and blindness suggests that they too benefit from instruction that emphasizes the critical elements of early literacy instruction for all children. Research also suggests that specific strategies, such as repeated readings, direct instruction in phonics, and big word decoding that emphasizes morphemes, can benefit school-aged children with visual impairments and blindness. Further research is needed if we are to understand fully the most effective approaches to emergent and early literacy instruction for children with visual impairments and blindness, but there is a solid base from which we can begin. PMID- 17340384 TI - Facilitating literacy development in young children with hearing loss. AB - Historically, children with hearing loss (HL) are often poor readers. In this article, the authors present two divergent groups of children with HL who have better than average literacy outcomes, children with Pervasive Exposure to Sign Language (PESL) and children who are Auditory-Verbal Communicators (AVCs). Outside-in and inside-in factors contributing to literacy development in the two groups of children are discussed with an emergent literacy perspective. Effective intervention strategies that can be used with all children with HL are highlighted. PMID- 17340385 TI - Toward evidence-based literacy interventions for children with severe and multiple disabilities. AB - Children with severe and multiple disabilities constitute a heterogeneous population that typically experiences significant and lifelong difficulties in learning to read and write. These difficulties appear to be both intrinsic and environmental in nature. Children with severe and multiple disabilities struggle particularly with vocabulary acquisition and phonological awareness. Home, preschool, and school environments may limit literacy learning opportunities by making literacy a lower priority than the child's competing health, self-care, and therapeutic needs; by providing limited access to adapted print materials or tools; by providing limited access to communication supports; or by providing little time for literacy learning. Children with severe and multiple disabilities who have demonstrated literacy learning progress are often taught in technology supported environments offering a wide range of word study, text-based reading and writing instruction, and opportunities for print exploration. Sufficient evidence exists for clinicians and educators to begin providing more successful literacy instruction to individual children and classrooms by comparing their children and intervention contexts with those reported in the limited body of research in this area. PMID- 17340386 TI - List of referees 1984. PMID- 17340387 TI - Effect of Chinese Herbal Medicine "Saiko-keishi-to" on Intracellular Calcium and Protein Behavior During Pentylenetetrazole-Induced Bursting Activity in Snail Neurons. AB - The Chinese herbal medicine "Saiko-Keishi-To" (SK), which is a mixture of nine crude drugs, shows a dramatic anticonvulsant effect in some difficult cases of epilepsy which had long been unsuccessfully treated by established anticonvulsant drugs. The anticonvulsant mechanism of SK was investigated from the viewpoint of intracellular calcium and protein behavior during bursting activity, which is characteristic of seizure discharge. SK clearly inhibited the intracellular calcium shift toward the cell membrane as well as the calcium binding state change near the cell membrane during bursting activity induced by pentylenetetrazole (PTZ). SK also inhibited the intracellular protein changes during PTZ-induced bursting activity together with the incorporation of calcium into these proteins. These findings suggest that the mechanism of anticonvulsant action of SK is closely related to pathologically induced intracellular calcium and protein changes during seizure activity. PMID- 17340388 TI - Spasmolytische wirkung des isoasaronfreien kalmus1. AB - ACORUS CALAMUS yields different drug types with varying content of beta-asarone, a substance which proved to be carcinogetic in rats. We tested essential oils with different beta-asarone content for their activity against histatnine-spasms in the isolated guinea pig ileum. At a dose level of 10 microg/cm (3), the beta asarone-free oil (type I) had a pronounced, spasmolytic activity which was comparable to that of the antihistaminic drug pyrilaminemaleate used as a standard antagonist (4 microg/cm (3). Each of these drugs changed the EC (50) for histamine from 29 microg/cm (3) to 118 microg/cm (3) approximately. At a dose level of 10 microg/cm (3) the beta-asarone-rich oil (type IV) showed no spasmolytic activity at all. The essential oil of the european calamus with low content of beta-asarone (type II) had also a good spasmolytic effect, however inferior to that of the beta-asarone-free oil, so that the above cited decrease of the EC (50) value of histamine could be seen in a concentration of 32 microg/cm (3). For this reasons and for better drug-safety, only the rhizomas of the beta-asarone-free diploid or of the triploid calamus with low content of beta asarone should be used. PMID- 17340389 TI - Phytochemical Study of Isoplexis chalcantha. AB - Three cardioactive glycosides were isolated from ISOPLEXIS CHALCANTHA. Two were identified as uzarigenin-canarobioside and uzarigenin-digilanidobioside, previously found in other Isoplexis. The third glycoside must be uzarigenin digitoxoside from the same source. The flavones apigenin, luteolin and their 7- Obeta- D-glycosides were also obtained, together with the salidroside [2-(4 hydroxyphenyl)-ethyl-1-beta- D-glucopyranoside]. PMID- 17340390 TI - An in vitro Study on the Effect of Momordica charantia on Glucose Uptake and Glucose Metabolism in Rats. AB - The effect of extracts of MOMORDICA CHARANTIA L. fruits on glucose metabolism and glucose uptake was investigated. The fruit of momordica, at all ripening stages, was found to contain two inhibitory compounds: one against hexokinase activity and the other against glucose uptake by rat intestinal fragments. Both inhibitions exhibit competitive profiles VERSUS glucose. The inhibitory factors are extractable in hot water, hot alcohol and hot acetone. A partial purification procedure by TLC for both inhibitors is described. PMID- 17340391 TI - Inhibition of mast cell histamine release by flavonoids and biflavonoids. AB - The effect of 11 flavonoids and 4 biflavonoids on the release of histamine from peritoneal rat mast cells induced by compound 48/80 and calcium ionophore A23187 was studied. Dihydroflavonoids (flavanones) and (+)-catechin did not modify histamine release induced by both secretagogues. Flavone, apigenin and cromoglycate inhibited the secretion elicited by compound 48/80 but did not modify the A23187-induced secretion. The effect of kaempferol on the compound 48/80-induced histamine release was biphasic. Low doses (10 (-6) to 10 (-5)M) of the compound potentiated secretion whereas higher doses inhibited histamine secretion. Some of the drugs tested revealed a higher potency as referred to quercetin. Luteolin, a tetrahydroxyflavone and amentoflavone, a biapigenin, exhibited the highest inhibitory effects of mast cell histamine secretion. PMID- 17340392 TI - In vitro and in vivo assessement of the antimalarial activity of sergeolide. AB - The antimalarial activity of sergeolide (a quassinoid from PICROLEMMA PSEUDOCOFFEA) was investigated both, IN VITRO on PLASMODIUM FALCIPARUM cultures and IN VIVO through a classical test of schizontocidal action against PLASMODIUM BERGHEI in mice. Sergeolide showed a very strong antiplasmodial activity IN VITRO as well as IN VIVO. Low concentrations (0.006 microg/ml) were able to fully inhibit the IN VITRO growth of chloroquine-sensitive and resistant strains of P. FALCIPARUM. Small amounts (0.26 mg/kg/day) markedly reduced the virulence of experimentally induced P. BERGHEI infection in mice. However, sergeolide, because of its high toxicity (LD 50: 1.8 mg/kg), does not seem, in its present form to be useful for malaria curative treatment. PMID- 17340393 TI - Novel Chromone Alkaloids from Schumanniophyton magnificum. AB - Six chromone alkaloids were isolated from the root bark of SCHUMANNIOPHYTON MAGNIFICUM Harms. Three of these were identified as the known alkaloids schumanniophytine, schumannificine and N-methylschumannificine. The other three alkaloids are novel and were named isoschumanniophytine, anhydroschumannificine and N-methylanhydroschumannificine. In addition it was seen that the N methylschumannificine isolated consisted of a mixture of two isomers and an alternative structure for schumanniophytine has been proposed. PMID- 17340394 TI - Central nervous depressant activity of valerenic Acid in the mouse. AB - Valerenic acid, isolated from VALERIANA OFFICINALIS L. s.l. affected the rotarod and traction performance of mice in a similar manner to that of pentobarbital which was used together with chlorpromazine and diazcpam as reference substance in both tests. A decrease of locomotility of mice was also noticed after administration of valerenic acid, in particular when this compound was administered to the same group of mice a week later than the vehicle. In addition valerenic acid was found to prolong the pentobarbital induced sleeping time. It can be concluded, that valerenic acid has aspecific central nervous depressent properties. This factor should be taken into account when considering the sedative action of Valerian preparations. PMID- 17340395 TI - Two Thymol Derivatives from Callilepis laureola. AB - The characterisation of two new thymol derivatives, found in the rootstock of CALLILEPIS LAUREOLA D C (Asteraceae), is reported together with that of a new ketol which was formed as a degradation product during the investigations. PMID- 17340396 TI - Pharmacological Studies on Linderae umbellatae Ramus, IV*. Effects of Condensed Tannin Related Compounds on Peptic Activity and Stress-Induced Gastric Lesions in Mice. AB - Nine condensed tannin related compounds isolated from LINDERAE UMBELLATAE Ramus, (+)-catechin ( 1), (-)-epicatechin ( 2), proanthocyanidin B-1 ( 3), B-2 ( 4), B-4 ( 5), trimer A ( 6), trimer B ( 7), cinnamtannin B (1) ( 8) and cinnamtannin D (1) ( 9), were tested for their effects on peptic activity and stress-induced gastric lesions in mice. Peptic activity of rat gastric juice was suppressed by 6 and 7 IN VITRO, and slightly suppressed by 8 and 9. In pylorus-ligated mice, these compounds, except for 4, administered orally exhibited anti-peptic activity. Pretreatments of 4,6 and 7 orally protected mice against stress-induced gastric lesions. Effects of these compounds on digestive systems were discussed. PMID- 17340397 TI - Sesquiterpene Lactones in the Molluscidal Extract of Eremanthus glomerulatus. AB - The eremantholides 1A, 1B, 1E, 1G, 1H, 1J and the germacranolides 2A, B were found in the molluscidal extract from EREMANTHUS GLOMERULATUS L. PMID- 17340398 TI - Phytoecdysteroids of Diploclisia glaucescens Seed. AB - Five phytoecdysteroids were isolated from the seeds of DIPLOCLISIA GLAUCESCENS and identified by spectrometric methods ( (1)H-NMR, (13)C-NMR and CIMS). One of them, 24- EPI- makisterone A, has not been reported before. The other four - 20 hydroxyecdysone, makisterone A, 24(28)-dehydromakisterone A and pterosterone - were known previously. The (13)C-NMR spectrum of 24(28)-dehydromakisterone A is presented for the first time. PMID- 17340399 TI - Antibiotics from Algae XXXIII1: Phlorotannins of the Brown Alga Himanthalia elongata2,3. AB - It is possible to obtain approximately 0.2% (relative to dry weight) phenols soluble in ethyl acetate from HIMANTHALIA ELONGATA. After removal of a fraction containing high-molecular weight substances, a total of 17 oligomeric phlorotannins with 2 to 8 aromatic rings can be isolated from the mixture of the acetylated phenol fraction. Apart from 2 derivatives belonging to the fucol group, diphlorethol and a tetraphlorethol not yet fully identified, all the other substances are fucophlorethols. Amongst these substances, a phenoxylated therphenyl derivative and several fucophlorethols with two-fold phenoxy substituted biphenyl moieties were identified for the first time. PMID- 17340400 TI - Studies on the endocrine effects of the contents of Cimicifuga racemosa:. AB - Endocrine activity can be demonstrated for components of the rhizome of CIMICIFUGA RACEMOSA using ovariectomized rats as experimental model. A selective reduction of the serum concentration of the pituitary luteinizing hormone (LH) takes place upon application of an extract. The active principle can be concentrated by extraction with dichloromethane. Enzymatic hydrolysis of glucosides leads to a significant loss of endocrine activity in the experimental model system of the ovariectomized rat. PMID- 17340401 TI - Assay methods for antihepatotoxic activity using peroxide-induced cytotoxicity in primary cultured hepatocytes1. AB - Conditions were investigated to devise IN VITRO assay methods for antihepatotoxic activity using peroxide-induced damage in primary cultured rat liver cells. Utilizing linoleic acid peroxide, benzoyl peroxide, cumene hydroperoxide and adenosine diphosphate/Fe (3+), satisfactory assay procedures were established. Some natural products known to exert liver-protective effects IN VIVO were screened to reveal that glycyrrhetinic acid, glycyrrhizin, cynarin, silybin and desoxypodophyllotoxin showed similar antihepatotoxic activity in these four assay methods. PMID- 17340402 TI - Antiinflammatory Compounds from Plagiorhegma dubium Cell Culture1. AB - Successive fractionation of a crude methanolic extract of cultured PLAGIORHEGMA DUBIUM cells, followed by assay of the biological activity using cobra venom factor induced paw oedema, led to the detection and isolation of three compounds with antiinflammatory activity. The substances were identified as the protoberberine alkaloid jatrorrhizine and the lignaneglucosides dehydrodiconiferyl-alcohol-4-beta- D-glucoside and its isomer dehydrodiconiferyl alcohol-gamma-beta- D-glucoside, the latter a compound not previously described in the literature. PMID- 17340403 TI - Isolation of (-)-Epicatechin from Pterocarpus marsupium and its Pharmacological Actions. AB - (-)-Epicatechin has been isolated from the bark of PTEROCARPUS MARSUPIUM Roxb (Leguminosae). This flavonoid compound was tested for its activity on central nervous system, isolated frog heart preparations and blood sugar levels of rats. Preliminary acute toxicity studies were also carried out. It was observed that ( )-epicatechin did not have any effect on central nervous system of rats and mice, (-)-epicatechin had shown both positive chronotropic and inotropic effects on frog hearts, the effect of which is blocked by propranolol. The compound in higher doses caused hyperglycemia in rats and this effect is also blocked by propranolol, showing adrenergic type of activity. (-)-Epicatechin was found to have no untoward effect even in higher doses. PMID- 17340404 TI - Effect of chinese herbal medicine "saiko-keishi-to" on transmembrane ionic current of snail neurons. AB - The effect of the Chinese herbal medicine "Saiko-Keishi-To" (SK) on transmembrane ionic current was examined to elucidate the mechanism of the anticonvulsant action of SK. SK caused a decrease in tramsmembarane sodium, calcium and potassium current. SK was also found to inhibit the negative resistance characteristics in an experiment using a voltage clamp with triangular command. PMID- 17340405 TI - Antihepatotoxic Actions of Ginsenosides from Panax ginseng Roots1. AB - The antihepatotoxic effects of ginsenosides, saponins from PANAX GINSENG, and their aglycones were investigated utilizing carbon tetrachloride (CCl (4))- and galactosamine (GalN)-induced cytotoxicity in primary cultured rat hepatocytes. Prominent protective actions were found with 20( S)-ginsenoside-Rh (2), 20( R) ginsenoside-Rg (3) and prosapogenin of ginsenoside-Ro, 20( R)- and 20( S) ginsenoside-Rs in CCl (4)-produced cytotoxicity, and 20( S)-ginsenoside-Rh (1) and prosapogenin of 20( S)-ginsenoside-Rs were effective in preventing GalN induced liver cell damage. The antihepatotoxic effects of chikusetsusaponins, saponins of PANAX JAPONICUS, were also examined. The structure-activity relationship is discussed. PMID- 17340406 TI - 2-Hydroxy-3,4-dimethyl-2-buten-4-olide as a Flavouring Component of Japanese Bai Zhi. AB - A characteristic flavouring compound, an isotetronic acid derivative (1), was isolated from "Japanese Bai Zhi" (Japanese name, "Wabyakushi", the root of ANGELICA DAHURICA Benth. et Hook. var. DAHURICA Benth. et Hook., Umbelliferae) and was identified as ( S)-2-hydroxy-3,4-dimethy1-2-buten-4-olide by chemical and spectral studies. PMID- 17340407 TI - Inhibition of lens-aldose reductase activity by brazilin and haematoxylin. AB - Brazilin and haematoxylin, plant pigments, were examined for their effects on the Bovine-Lens aldose reductase (LAR)-activity. About 50% inhibition was observed in a concentration of 10 (-4) M-brazilin and 10 (-4) M-haematoxylin, and above 95% inhibition was observed in a concentration of 10 (-3) M-brazilin and 10 (-3)M haematoxylin. In order to determine the type of inhibition, kinetic studies were also conducted with brazilin and haematoxylin, in which both were found to be noncompetitive inhibitors. PMID- 17340408 TI - A new bisbenzylisoquinoline alkaloid from a peruvian curare. AB - From a Peruvian curare a new bisbenzylisoquinoline alkaloid, ( R,S)-nor-N (b) chondrocurine, 1, was isolated together with the known ( R,R)-curine, 2, (R,S) chondrocurine, 3, and tubocurarine (as chloride), 5. (13)C-NMR data of 1, 2 and of ( R,S)-di-methylchondrocurine, 4, are reported. PMID- 17340409 TI - Hypolaetin-8-O-Glucoside, An Anti-inflammatory Flavonoid from Sideritis mugronensis. PMID- 17340410 TI - Soyasaponin-I from the Roots of Arachis hypogaea. PMID- 17340411 TI - Alkaloids from Seeds of Iphigenia stellated1. PMID- 17340412 TI - Indole Alkaloids from Multiple Shoot Cultures of Rauwolfia serpentina. PMID- 17340414 TI - Further Germacranolides from Eupatorium serotinum. PMID- 17340413 TI - Further guaianolides from saussurea species. PMID- 17340415 TI - A Further Dithienyl Derivative from Porophyllum scoparia. PMID- 17340416 TI - Iridoids of guyanese species of stigmaphyllon. PMID- 17340458 TI - Preface: platelets in inflammation and atherothrombosis. PMID- 17340459 TI - Platelet-leukocyte interactions in inflammation and atherothrombosis. AB - Inflammatory processes at the vascular wall result in the development of atherosclerosis. Platelet interactions with leukocytes may play a key role in the initiation of inflammation. They trigger autocrine and paracrine activation processes, leading to leukocyte recruitment (in)to the vascular wall. This article highlights the molecular basis and the inflammatory pathways initiated by platelet-leukocyte interactions. PMID- 17340460 TI - Platelets and endothelial cells. AB - The pathogenesis of atherosclerosis, the leading cause of morbidity and mortality in industrial countries, is multifactorial. Atherogenesis, the development of atherosclerotic lesions, is initiated by a mechanical or functional injury of the endothelium. The function of the endothelium is influenced by multiple factors as a consequence of cell-cell interactions. Cell-cell communication between endothelial cells with platelets has only recently begun to receive systematic study. In recent years it has been established that platelet-endothelial interactions are involved at all stages of atherosclerotic disease. This article reviews the interactions between endothelial cells and platelets in the context of their role to initiate and accelerate atherothrombosis, as well as in acute thrombotic occlusion (e.g., at the site of atherosclerotic plaque rupture or subsequent to coronary angioplasty). From a mechanistic standpoint, platelets and endothelial cells communicate on multiple levels. Cross-talk may occur over a distance (paracrine signaling), via transient interactions (so-called give-and-go mechanism), or through receptor-mediated cell-cell adhesion. Platelets may release or transfer substances that influence endothelial cell function, and vice versa. Among many others, adhesion molecules, such as P-selectin (CD62P), are of special interest because of their role in modulating interactions between blood cells and the endothelium, and also because of the possible use of the soluble form as a plasma predictor of adverse cardiovascular events. In addition to dietary, cholesterol and lipid lowering, and other pharmaceutical approaches, antiplatelet therapy plays an important part in the treatment of atherosclerosis and its multifactorial clinical manifestations. Understanding the specific interactions between platelets and the endothelium may lead to the development of novel therapeutic strategies. PMID- 17340461 TI - Platelet-induced differentiation of endothelial progenitor cells. AB - Endothelial progenitor cells (EPCs) have the potential to home at sites of vascular lesions and to contribute to revascularization. This homing is a highly concerted mechanism, which involves chemotaxis, adhesion, migration, and finally integration of the cells into the target tissue. Only recently has the platelet been identified as a central mediator of EPC homing. Adherent platelets were able to mediate chemotaxis and adhesion of EPCs, a process that involved P-selectin glycoprotein ligand 1 and very late antigen-4 (VLA-4). Recent studies suggest that platelet-derived stromal cell-derived factor-1 is also involved centrally in the recruitment of EPCs. Furthermore, platelets induce progenitor cell migration by platelet-derived growth factor AB. Recent in vivo data confirm the recruitment of EPCs to sites of vascular lesions after vessel denudation by activated platelets and fibrin. Moreover, when coincubated with platelets, EPCs differentiate to mature endothelial cells and have the potential to migrate and colonize a platelet thrombus. The described interaction of EPCs with platelets represents a novel mechanism of vascular remodeling and healing of endothelial lesions. PMID- 17340462 TI - The active platelet: translation and protein synthesis in an anucleate cell. AB - Platelets are the major cellular component of the hemostatic system that controls vessel and wound repair. However, platelets also have a variety of additional functions in inflammatory responses and host defense. The function and structure of the platelet was assumed to be very simple for a long period of time. With more modern tools of investigation such as cDNA arrays and proteomics, we have discovered a cell that is becoming a more sophisticated libero that functions in the classic mechanisms of white blood cells--inflammation and immunity. PMID- 17340463 TI - Where is the trace? Molecular imaging of vulnerable atherosclerotic plaques. AB - Serious cardiovascular events frequently arise from rupture of vulnerable atherosclerotic plaques. Not infrequently, these plaques are clinically silent and suddenly cause acute complications such as myocardial infarction, which in a high percentage are fatal. Thus, identifying individual patients with vulnerable plaques at high risk for plaque rupture is a central challenge in clinical medicine. This review highlights noninvasive scintigraphic techniques, which use radiolabeled molecules to detect functional aspects in atherosclerotic plaques by visualizing their biological activity. One major principle is the molecular imaging of inflammation with radionuclide tracers, including detection of metabolic activity, chemotaxis, cell recruitment, and lipoprotein enrichment. Additional studies focus on visualization of apoptosis, angiogenesis, or proteolysis. A central feature of plaque vulnerability is its thrombogenicity. Therefore, detection of thrombogenic plaques is another promising principle of molecular imaging. If a reliable protocol to image vulnerable plaques, which are prone to rupture, can be established and introduced into clinical practice, the required measures such as atheroprotective medication or revascularization could be undertaken to prevent serious cardiovascular events. PMID- 17340464 TI - Platelets and stromal cell-derived factor-1 in progenitor cell recruitment. AB - Stromal cell-derived factor-1 (SDF-1) is a CXC chemokine that binds to its sole counterreceptor, CXCR4. It is well reported that the SDF-1/CXCR4 signaling pathway is of vital importance to human development and to various pathophysiological phenomena, including hematopoiesis, angiogenesis, atherosclerosis, cancer growth, metastasis, and human immunodeficiency virus infection. SDF-1 promotes mobilization of bone marrow-derived endothelial progenitor cells (EPCs) to the circulation in response to vascular injury. Recently, we found that platelets express and release SDF-1 into the microcirculation upon activation and we observed that platelet-derived SDF-1 is functionally involved in recruitment of EPCs to arterial thrombi in vivo. This review discusses the unique functions of this chemokine and the newly discovered impact of platelet-derived SDF-1 into the recruitment of progenitor cells to vascular injury areas, and its subsequent effects in atherosclerosis, vascular repair, and angiogenesis. PMID- 17340465 TI - Molecular imaging of vulnerable plaque by cardiac magnetic resonance imaging. AB - Coronary atherosclerosis is known to be the major cause for morbidity and mortality in the industrial world. In Europe, every year approximately 600,000 persons die from coronary artery disease, a majority of them without any prior symptoms. Plaque rupture, mostly of noncalcified vulnerable plaques, is supposed to play a major role in this setting, and noninvasive techniques are mandatory to stratify the individual risk for experiencing an acute coronary event. During the last decade, magnetic resonance imaging has gained importance as a noninvasive imaging technique in cardiology. Continuous technical improvements enabled a rapidly expanding field of application, and recently noninvasive imaging of plaques has been introduced. In addition to morphological characterization, functional imaging of plaques has gained interest for a more specific risk assessment. This article summarizes pathophysiological aspects of the concept of vulnerable plaque, technical requirements for noninvasive plaque imaging, and characterization with magnetic resonance imaging. PMID- 17340466 TI - The evil in atherosclerosis: adherent platelets induce foam cell formation. AB - Platelet interaction with circulating progenitor cells plays an important role for repair mechanisms at sites of vascular lesions. Foam cell formation represents a key process in atherosclerotic plaque formation. We revealed that platelets regulate recruitment and differentiation of CD34 (+) progenitor cells into foam cells and endothelial cells. Adhesion studies showed that platelets recruit CD34 (+) progenitor cells via specific adhesion receptors, including P selection/P-selectin glycoprotein ligand 1, and beta (1) and beta (2) integrins. CD34 (+) progenitor cells were coincubated with human platelets for 1 week. We demonstrated that a substantial number of CD34 (+) cells differentiated into foam cells. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and agonists of peroxisome proliferator-activated receptor-alpha and -gamma (PPAR alpha and -gamma agonists) reduced this foam cell generation via inhibition of matrix metalloproteinase 9 secretions. Foam cell formation is also induced by low density lipoproteins (LDLs). It was revealed that platelets take up modified LDL (fluorochrome-conjugated acetylated LDL) that is stored in the dense granules and internalized rapidly into the foam cells. These findings emphasize that the balance between endothelial cell regeneration and platelet-mediated foam cell generation derived from CD34 (+) progenitor cells may play a critical role in atherogenesis and atheroprogression. PMID- 17340467 TI - Platelet glycoprotein VI: a novel marker for acute coronary syndrome. AB - The platelet collagen receptor glycoprotein (GP) VI is critical for the formation of arterial thrombosis. GPVI platelet surface expression was examined in patients with stable angina and in patients with acute coronary syndrome (ACS). Surface expression of platelet activation markers such as P-selectin, GPIbalpha, and platelet GPVI was determined by flow cytometry. Patients with ACS showed a significantly enhanced GPVI expression compared with patients with stable angina and healthy controls. The expression of GPVI correlated well with CD62P. Elevated platelet GPVI expression was associated with ACS independent of markers of myocardial necrosis such as troponin and creatine kinase. In ACS, platelet surface GPVI expression was already elevated several hours before troponin and creatine kinase indicated myocardial injury. We conclude that the determination of the platelet-specific thrombotic marker GPVI may help to identify patients at risk before myocardial ischemia is evident. PMID- 17340468 TI - Single-chain antibodies as new antithrombotic drugs. AB - Antibodies are the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. At present, several antibodies are approved for therapeutic use in diverse clinical settings, including oncology, chronic inflammatory diseases, transplantation, infectious diseases, and cardiovascular medicine. These approved antibody therapeutics include unmodified immunoglobulin G molecules, radioimmunoconjugates, antibody-drug conjugates, and fragment antigen-binding molecules. At least 150 additional antibodies are in clinical development. A major strength of therapeutic antibodies is their established properties as a drug class with high success rates from clinical trials to regulatory approvals. Much of the experience gained from the generation and optimization of one antibody is applicable to other antibodies. Antibody fragments are a subclass with growing clinical importance. This review focuses on single-chain antibodies as the smallest possible format for recombinant antibodies, and their use as antithrombotic drugs. We describe different antibody formats, the current applications of antibody fragments, and their generation by cloning from hybridoma cell lines as well as their selection from antibody libraries. We review the use of antibody fragments for thrombus targeting using fibrin and platelet-specific single-chain antibodies in combination with anticoagulants and thrombolytic agents as antithrombotic drugs. PMID- 17340469 TI - Variable response to clopidogrel in patients with coronary artery disease. AB - Antiplatelet drug resistance is a multifactorial phenomenon that affects a large number of cardiovascular patients with symptomatic coronary artery disease. Although unique definitions for aspirin and clopidogrel resistance are missing, there is growing evidence for a clinical importance of response to antiplatelet therapy. The prevalence for aspirin and clopidogrel resistance has been reported to be between 5 and 30% in literature. Moreover, recent data suggest a high rate of dual antiplatelet drug resistance. Although there are convincing data about an association of aspirin resistance and clinical outcome, little is known about the clinical relevance of clopidogrel hyporesponsiveness. This article reviews the evidence for the clinical impact of antiplatelet drug resistance, with particular attention on the clinical outcome of clopidogrel low response according to current clinical data. Additional systematic studies are needed to evaluate the effects of alternative antiplatelet therapies in patients identified as low responders. PMID- 17340470 TI - Noninvasive plaque imaging using multislice detector spiral computed tomography. AB - Multislice detector spiral computed tomography (MSCT) is a noninvasive modality for visualization and evaluation of atherosclerosis in vivo in different arterial beds. Rapid technical advances led to a significant improvement of the diagnostic accuracy of coronary MSCT angiography. The most popular clinical application with best scientific Medical evidence of MSCT is the noninvasive detection and quantification of coronary calcifications. In particular, the concept of determining coronary artery age by evaluating an individual's biological age, rather than his or her chronological age, is attractive and currently under scientific evaluation. In addition to evaluating contrast-enhanced coronary arteries, different stages of atherosclerosis can be visualized. By comparative studies with intracoronary ultrasound, it could be shown that echogenicity corresponds well with the density measured within atherosclerotic plaques expressed by Hounsfield units using MSCT. Although the method is improving continuously and is still under development, the potential of MSCT to evaluate plaque composition and plaque volumes noninvasively in vivo is promising. PMID- 17340471 TI - Aspirin resistance: does it exist? AB - Aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1). Aspirin sensitivity can be measured easily by its inhibition of arachidonic acid (AA) induced platelet aggregation. Aspirin resistance has to be defined by its inability to inhibit COX-1. By using this definition, aspirin resistance very likely does not exist. A specific rapid laboratory test using either AA-induced platelet aggregation or AA-induced malondialdehyde production in platelet-rich plasma is needed to test aspirin sensitivity. The reports on so-called aspirin resistance are usually due to noncompliance of aspirin intake or consumption of inadequate doses of aspirin. In addition, data generated from using nonspecific platelet function tests have added confusion to this observed phenomenon of aspirin resistance. PMID- 17340472 TI - On "Composition, Quality Control, and Labeling of Plasma-Derived Products for the Treatment of von Willebrand disease" (Semin Thromb Hemost 2006;32: 529-536). PMID- 17340515 TI - Anti-Inflammatory Effect of Neolignans Newly Isolated from the Crude Drug "Shin i" (Flos Magnoliae). AB - The anti-inflammatory effects of the major components of the dried flower buds of MAGNOLIA SALICIFOLIA were determined using the pouch granuloma method in mice. Though alkaloids, fatty acids, essential oils, and lignans had no anti inflammatory effects, neolignans (magnoshinin and magnosalin) significantly inhibited the granuloma tissue formation. The inhibitory effect of magnoshinin was particularly strong, being nearly half of that of hydrocortisone acetate when administered orally. Some differences were noted in the mode of action between the neolignans and the steroidal drugs as the neolignans selectively inhibited the granuloma tissue formation but did not affect the exudation of pouch fluid. The structural specificity of neolignans was also found on their anti inflammatory effect. PMID- 17340516 TI - Structural Features of Plantago lanceolata Mucilage. AB - The water soluble crude polysaccharide fraction from PLANTAGO LANCEOLATA leaves is composed of L-arabinose (20%), D-galactose (28%), D-glucose (6%), D-mannose (2%), L-rhamnose (4%), D-galacturonic acid (31%), D-glucuronic acid (7%) and minor amounts of L-fucose and D-xylose. The total polysaccharide extract could be separated on DEAE-cellulose into three distinct polysaccharide fractions, two of which, FI (neutral) and FII (acidic), were subjected to further structural investigations. While FI could be fractionated into two subfractions (FIa, MW: 8000; FIb, MW: 25000) by gel chromatography, FII proved to be homogeneous (MW: 70000). Analysis of component sugars, reduction and methylation, (13)C-NMR spectroscopy and partial acid degradation studies made it possible to suggest the structural repeating units for the polysaccharides in FI and FII. PMID- 17340517 TI - Dibenzocyclooctadiene Lignans from Roots and Stems of Kadsura coccinea. AB - Ten dibenzocyclooctadiene lignans were obtained from the ethereal soluble fraction of the dried roots and stems of KADSURA COCCINEA. Two of them were new compounds, named kadsutherin ( 8) and isokadsuranin ( 10). Their structures were elucidated on the basis of chemical and spectral analysis. PMID- 17340518 TI - Polyindolinic Alkaloids from Psychotria forsteriana. Potent Inhibitors of the Aggregation of Human Platelets. AB - Quadrigemine B, quadrigemine A, isopsychotridine C and psychotridine, isolated from PSYCHOTRIA FORSTERIANA, are potent inhibitors of the aggregation of washed human platelets induced by ADP, collagen or thrombin. The four compounds are active in the 1-10 microM range. The quadrigemine-type alkaloids do not increase the level of platelet cyclic AMP, either alone or in the presence of 20 nM prostaglandin E, (PGE (1)), an activator of adenylate cyclase. The characteristics of the pharmacological action of these compounds suggest that they act at a later stage in platelet activation, possibly through an interaction with cytoskeletal proteins. PMID- 17340519 TI - Yuehchukene, a Novel Anti-implantation Indole Alkaloid from Murraya paniculata. AB - Yuehchukene, 11beta-(3'-indolyl-7,9alpha,9beta-trimethyl-5beta,8,9,10beta tetrahydroindano-[2,3- B]indole, a novel dimeric indole alkaloid from the roots of MURRAY A PANICULATA has potent anti-implantation activity in rats at 3 mg/kg P. O. dosing on pregnancy day 2. PMID- 17340520 TI - Antibiotics from Algae. XXXV. Phlorotannins from Ecklonia maxima1. AB - New phloroglucinol derivatives were isolated from the ethanolic extract of ECKLONIA MAXIMA, a brown alga found off the west coast of South Africa. Most of these compounds contain dibenzo[1,4]dioxin elements. The common basic unit of all the compounds found is eckol, a hexahydroxyphenoxydibenzo[1,4]dioxin composed of 3 phloroglucinol units. Phloroeckol A and B represent four-ringed phloroglucinol derivatives, whereas the only five-ringed substance (furodehydroeckol) displays a furan structure in addition. Six-ringed phloroglucinol derivatives composed of two eckol units joined either symmetrically (such as 7,7'-bieckol, 9,9'-bieckol) or asymmetrically (7,9'-bieckol, dieckol) are found frequently. Apart from these, tetraphlorethol C, a four-ringed tetraphloroglucinol triether which lacks both dioxin and furan structures, also occurs. PMID- 17340521 TI - Aus glycosidischer Bindung freigesetzte und genuin frei vorliegende Komponenten des etherischen Ols von Solanum tuberosum sowie Artefaktbildung bei seiner Gewinnung1. AB - The composition of essential oils of SOLANUM TUBEROSUM obtained by different methods was investigated. It could be shown that the essential oil is mainly composed of sesquiterpenes. The monoterpene linalool was found to be glucosylated. PMID- 17340522 TI - Studies on the endocrine effects of the contents of Cimicifuga racemosa 2. In vitro binding of compounds to estrogen receptors. AB - The endocrine activity of compounds of the rhizome of CIMICIFUGA RACEMOSA can be demonstrated in the IN VIVO model of the ovariectomized rat as well as in the IN VITRO system of the estrogen receptor assay. A reduction of the serum levels of luteinizing hormone in ovariectomized rats takes place upon application of a methanol-extract. This extract contains substances, which are able to bind to estrogen receptors of rat uteri. Using the estrogen receptor assay as a pharmacological testsystem to determine the activity of different fractions, the chromatographic separation of the methanol-extract resulted in at least three different endocrine active compounds. One of these could be identified as the isoflavon Formononetine. The endocrine activity of this isoflavon was characterized in both described testsystems. It can be shown that Formononetine is a competitor in the estrogen receptor assay, but failed to reduce the serum levels of luteinizing hormone in overiectomized rats. PMID- 17340523 TI - Separation and Quantification of Some Alkaloids from Fumaria parviflora by Capillary Isotachophoresis1. AB - The isotachophoretic separation of some isoquinoline alkaloids in acid-base partially purified extracts from Bulgarian FUMARIA PARVIFLORA was studied. The electrolyte system for model mixtures of alkaloids (-)-stylopine, (-)-canadine, coptisine, berberine, protopine, cryptopine, chelidonine, bulbocapnine, papaverine, parfumine and for the plant extracts contained the leading ion K (+) (0.01 M), counter ion CH (3)COO (-), pH (L) 5.5, and the terminating ion H (+) (acetic acid 0.01 M). In the plant extracts, protopine and parfumine were quantitatively determined during F. PARVIFLORA growth and development in the term May-June 1984. PMID- 17340524 TI - Isolation of Spinasterol and its Glucoside from Cell Suspension Cultures of Saponaria officinalis: 13C-NMR Spectral Data and Batch Culture Production. AB - Spinasterol and spinasteryl glucoside have been isolated as the exclusive sterols from cell suspension cultures of SAPONARIA OFFICINALIS and identified by MS, (1)H NMR and (13)C-NMR spectral data. This result confirms the taxonomical vicinity of this plant to Chenopodiaceae and Amaranthaceae where Delta (7)-sterols were also described to be present. With more than 44% of total sterol content, the spinasteryl glucoside content is higher than in most of the common plants. This shows a particularly active glycosylation process probably in relation with the biosynthesis of saponosides. PMID- 17340525 TI - Antiinflammatory actions of ephedrines in acute inflammations1. AB - Ephedrine (EP), pseudoephedrine (PEP), ephedroxane (EX) and pseudoephedroxane (PEX) inhibited carrageenin-induced hind-paw edema in sham-operated mice as well as adrenalectomized mice. Hind-paw edema induced by histamine, serotonin, bradykinin and prostaglandin E (1) was suppressed by these alkaloids, showing that they exert the antiinflammatory activity at the early exudative stage of inflammation. Although tolazoline and propranolol had no effects on the inhibitory activity of EX and PEX, treatment with tolazoline decreased the antiinflammatory activity of EP and PEP on carrageenin-induced hind-paw edema. Antiinflammatory activity of PEP was reduced by previous treatment with reserpine, indicating the antiinflammatory activity of EP and PEP to be partly concerned with the sympathetic nervous system. Although these alkaloids injected I.C.V. elicited no antiinflammatory actions on carrageenin-induced hind-paw edema and the inhibitory activity of morphine on carrageenin-induced hind-paw edema was potentiated by the concurrent administration of PEP and EX, demonstrating that the mechanism of antiinflammatory activity does not involve the central nervous system. Further, these alkaloids inhibited prostaglandin E (2) biosynthesis. PMID- 17340526 TI - Mechanism of antihepatotoxic activity of wuweizisu C and gomisin A1. AB - The mechanism of inhibitory action of wuweizisu C and gomisin A in carbon tetrachloride (CCl (4))-induced liver damage was investigated by determining the effects of these substances on the steps of the series of events leading to liver lesion. Although wuweizisu C and gomisin A exerted no inhibition in CCl (3) radical formation, both lignans inhibited CCl (4)-, ADP/Fe (3+)- and ascorbate/Fe (2+)-induced lipid peroxidation, and wuweizisu C elicited stronger effects than gomisin A which is parallel with the results on antihepatotoxic effects in CCl (4)-induced cytotoxicity, indicating that anti-oxidative action plays an important part in the antihepatotoxic activity of wuweizisu C and gomisin A. PMID- 17340527 TI - A New Triterpenoid Sapogenin of Epoxy Serratane Type from Primula rosea. AB - A new sapogenin 14beta, 26-epoxy serratane-3beta, 21alpha-diol has been isolated and characterized in addition to glucose, galactose and rhamnose from PRIMULA ROSEA. PMID- 17340528 TI - Composition of Essential Oils of Thymbra spicata and Satureja thymbra Chemotypes1. AB - The essential oils of THYMBRA SPICATA and SATUREJA THYMBRA growing wild in Israel were investigated by means of GLC and GC-MS. The main components of the oils were carvacrol, thymol, gamma-terpinene and P-cymene. Eleven monoterpene hydrocarbons, two sesquiterpene hydrocarbons and nine oxygenated monoterpenes were identified. PMID- 17340529 TI - Isolation and Hypoglycemic Activity of Ganoderans A and B, Glycans of Ganoderma lucidum Fruit Bodies1. AB - A water extract of the Oriental crude drug "reishi", the fruit bodies of GANODERMA LUCIDUM, significantly decreased plasma sugar level in mice. Fractionation of the extract by monitoring the hypoglycemic activity afforded two glycans, ganoderans A and B. These glycans elicited remarkable hypoglycemic actions in normal and alloxan-induced hyperglycemic mice. PMID- 17340530 TI - New Clerodane Derivatives from Teucrium scordium. AB - A reinvestigation of the aerial parts of TEUCRIUM SCORDIUM afforded in addition to several known diterpenes five new clerodane derivatives, all closely related to teucrin. The structures and the stereochemistry were elucidated by high resolution (1)H-NMR spectroscopy. PMID- 17340531 TI - Cardiac Glycosides from the Roots of Streblus asper. AB - A new cardiac glycoside "vijaloside" in addition to well known cardenolide, asperosid (digitoxigenin-2',3'-di- O-methylglucopyranoside) have been isolated and identified from the roots of STREBLUS ASPER. Repeated chromatgraphic manipulations and spectral analysis (IR, (1)H-NMR, (13)C-NMR and Mass), suggested the structure of vijaloside as periplogenein-3- O-beta- D-glucopyranosyl (1 --> 5)- O-beta- D-xylofuranoside. PMID- 17340532 TI - Alkaloids of Androcymbium melanthioides var. stricta1. AB - The aerial parts of ANDROCYMBIUM MELANTHIOIDES yielded known alkaloids cornigerine, colchicine, N-formyl- N-deacetylcolchicine, 2-demethylcolchicine, 3 demethylcolchicine, demecolcine, 2-demethyldemecolcine, 3-demethyldemecolcine, beta-lumicornigerine, beta-lumicolchicine, gamma-lumicolchicine, androcymbine, O methylandrocymbine, and melanthioidine. Of these, O-methylandrocymbine and beta lumicornigerine are reported for the first, time. The alkaloid, formerly designated as compound AM-3, has been identified as N-deacetyl- N-dimethyl-gamma lumicornigerine 1. Its spectral data are given. PMID- 17340533 TI - Plant Anticancer Agents XXXVII. Constituents of Amanoa oblongifolia1. AB - 4'-Demethyldeoxypodophyllotoxin was isolated as the sole cytotoxic constituent of a chloroform-soluble extract of the stem bark of AMANOA OBLONGIFOLIA. Also identified from this extract were a number of noncytotoxic isolates that comprised the lignans, (+)-sesamin and paulownin, the triterpenes, friedelin, canophyllol, betulin, betulinic acid, and ursolic acid, and the sterols, beta sitosterol and daucosterol. PMID- 17340534 TI - Plant Anticancer Agents XXXV. Further Constituents of Simaba multiflora1,2. AB - An antileukemic quassinoid simalikalactone D ( 17) and two anticancer phenolic compounds, emodin and tricin, were isolated from the wood of SIMABA MULTIFLORA (Simaroubaceae) as well as 8-hydroxycanthin-6-one ( 18) and coumarin. The constituents of the genus SIMABA are reviewed. PMID- 17340535 TI - Conversion of nitroheptane to dihydrojasmone. AB - The synthesis of dihydrojasmone ( 4) from 1-nitroheptane via 5-nitro-2-undecanone is described. It is not necessary to transform the second nitro to a ketone group to give 2,5-undecadione. A direct transformation procedure is given. PMID- 17340536 TI - 6-Oxocycloartan-3beta, 16beta-diglucoside: A New Cycloartane Diglucoside from Astragalus trigonus. AB - A new saponin glycoside has been isolated from ASTRAGALUS TRIGONUS collected in Egypt and identified as 6-oxocycloartan-3beta,-16beta-di- O-glucopyranoside on the basis of an analysis of spectral data from the parent compound and its peracetate. PMID- 17340537 TI - Isolation of Prostratin from Euphorbia cornigera. PMID- 17340538 TI - Further Diterpenes from Stem Bark of Xylopia aethiopica1. PMID- 17340539 TI - The Cytotoxic Principle of Scutellariae Radix against L1210 Cell. PMID- 17340540 TI - Isolation of 4,8-Dihydroxy-6-methyl-1-tetralone from the Root Bark of Euclea natalensis. PMID- 17340541 TI - [Reflections on nursing education in Taiwan and its prospects from the perspective of nursing manpower policy]. AB - The purpose of this paper is to propose a vision and appropriate policy development strategies for nursing manpower in Taiwan. Proposals are grounded in a comprehensive analysis of Taiwan's current nursing manpower policy problems based on the linkages between nursing education and nursing practice. Nursing manpower policy goes beyond concern for simple numbers to include other variables that affect nursing staffs such as workload, work environment, case complexity, skill level, nursing staff mix, and nursing care cost efficiency and effectiveness. Manpower, the most important and precious resource in the medical care system, is the critical factor affecting the system's capacity to deliver appropriate and effective care. In recent years, demand for nurses in developed countries has fallen short of domestic supply, which has raised international nursing migration levels. The International Council of Nurses pursues policy issues related to nursing manpower. Although it has not yet experienced a shortage of nurses, Taiwan still lacks comprehensive policy and management systems governing nursing manpower. PMID- 17340542 TI - [Reflections on nursing education in Taiwan and its prospects from the perspective of adult education]. AB - Globalization, lifelong learning concepts and increasing numbers of adults in recurrent education programs all underscore the need for nursing education to train students in interpersonal, knowledge acquisition, task accomplishment and personal development skills applicable to both their work and everyday life. Today, our technology-driven world produces and rapidly disseminates vast amounts of information. So-called "academic knowledge" is no longer adequate to teach nurses how to perform routine nursing care duties. Therefore, recurrent education has taken a central role in nursing education. Grounded in adult education theory, this article discusses the current state of nursing education in Taiwan and proposes practical suggestions for the future. Such suggestions include: 1) a recurrent education curriculum should instill in students a commitment to lifelong learning; 2) learning through problem posing, instead of lectures, should be promoted in order to foster an interactive relationship between teacher and student that is characterized by critical thinking and active dialogue; 3) modern technology now permits information technology skills to become a core competency in nursing; and 4) nursing education should foster a global view in order to consider how to use the experience and knowledge of other countries' to enhance domestic nursing knowledge and practices. PMID- 17340543 TI - [Prospective developments in nursing education from the perspective of current dilemmas]. AB - Nursing education has evolved from the apprentice system into today's formal doctoral programs. However, has the elevated status of nursing education necessarily led to qualitative improvements? This paper focuses on the crisis and myths related to the nursing education paradigm, the evolution and ongoing reform of nursing education, as well as its future prospects. PMID- 17340544 TI - [Learning of life cultivation through nursing education]. AB - This paper focuses on the learning of life cultivation through nursing education. Three perspectives are described, including (1) the learning of life cultivation, (2) the systematic approach to educational design, and (3) the faculty model of nursing clinical competency. It hoped that this study helps facilitate the learning of core values, fosters respect for life and encourages self expression in the nursing profession. PMID- 17340545 TI - [Humanity education in nursing]. AB - Nurses play a pivotal role in caring for people. Since every person is unique, providing holistic care is central to the nursing profession. Rapidly advancing technology and the rise of cost-oriented healthcare management have, nevertheless, changed the nurse-patient dynamic and, created new challenges for the nursing profession. It is believed that cultivating humanism in nursing education can sustain nurses' adherence to patient-centered care amidst rapid changes in the health care system. Humanity education can further help nurses develop deeper insights into their own values and life experiences and, in turn, assist them to deal with life and work-related frustrations more effectively. Through a review of the literature, the authors tried to identify content and strategies central to successful humanity education for nursing students. At the end of this article, some suggestions are proposed for the future development of humanity education within Taiwan's nursing community. PMID- 17340546 TI - [The participation experiences of localized prostate cancer patients in the treatment decision-making process]. AB - The purpose of this study was to investigate the participatory experience in the treatment related decision-making process of patients receiving radical prostatectomy or high-dosage brachytherapy for localized prostate cancer. Between March 2005 and May 2005, ten patients diagnosed with localized prostate cancer were recruited by purposive sampling at a medical center outpatient department and ward and included in this study, based on a qualitative study design. Semi structured, guided interviews were employed to collect data. Data were analyzed by content analysis. Results showed that the decision-making experience of these localized prostate cancer patients included the items of greatest concern to patients as well as addressed the factors that made treatment decision-making difficult. Findings may be referenced by medical personnel when they are charged to select optimal treatment options for patients with prostate cancer. PMID- 17340547 TI - [An exploratory study of psychiatric patients' needs and nurses' current practices related to sexual counseling]. AB - The purpose of this study was to explore psychiatric patient needs and current nursing practice with regard to sexual counseling and to understand differences in individual patient characteristics. A total of 182 psychiatric patients and 44 psychiatric nurses were purposively selected from a mental hospital in northern Taiwan. Results revealed that 63.2% of subjects had not been given sexuality information and 81.9% had not been approached by nurses to discuss such issues. While 35.2% of study patients treated sexual issues as psychological or private issues that should only be discussed with psychologists, 33.5% expressed a desire to discuss issues related to sexuality with nurses. Even so, most subjects preferred to discuss sexual issues in a private way, and asked for assistance from same-gender professionals. Also, patients with higher education levels placed greater attention on the counseling topics of how to express sexual needs and the impacts of mental illness on sexuality. With regard to nurses participating in the study, female nurses had a generally more conservative attitude toward sexual values than males. Those who were married, older, or had received continuing sexuality education were more comfortable with conducting sexual counseling. Those with clinical experience and continuing sexuality education were able to take more responsibility and a more professional role in sexual counseling. Data collected on the specific subject groups in order to provide effective comparisons can be employed to refine current sexual counseling training programs for nurses in order to improve patient care. PMID- 17340548 TI - [Subjective quality of life in patients undergoing long-term maintenance hemodialysis treatment: a qualitative perspective]. AB - The purpose of this qualitative study was to explore the subjective "quality of life" experience of patients undergoing long-term maintenance hemodialysis treatment at a southern Taiwan hospital. A purposive sample of fourteen patients was selected to participate in in-depth audio-taped interviews. Data were analyzed using the content analysis method. Findings delineated five quality of life themes and ten sub-themes for hemodialysis patients. These included: (1) Physical functions (normal life disrupted by physical symptoms, lack of vigor); (2) Psychological functions (emotional instability, impaired sense of self); (3) Social functions (dependence upon family, restricted lifestyle and social life); (4) Economic status (fewer work opportunities, financial needs covered by the National Health Insurance); and (5) Overall quality of life (perceived poor quality of life, reluctant acceptance of situation). Study findings may help health professionals implement appropriate interventions as well as provide a working outline for social workers. In addition, findings may be referenced in the revision and further development of national health insurance policies. PMID- 17340549 TI - [A project to improve the screening rate of pap smear for cervical cancer]. AB - The incidence of cervical cancer in Taiwan is high and ranks as the seventh highest in the world. However, only 28.4% of the women in Kaohsiung underwent Pap smear screening. Ironically, the screening rate for female patients in our hospital was even lower at 13.2%. As medical staff in a public, community hospital, we have the responsibility to promote the health of our residents. The aim of this project was to increase the Pap smear screening rate to 28.0% in our community. The prior data analysis revealed that the low rate of Pap smear screening was related to inadequate information about the Pap smear, poor health knowledge among the women in this community, long processing time (50.86 +/- 5.88 minutes), inconvenient accessibility, and the lack of good explanation from our medical staff. The situation has significantly improved after we made adjustments including: providing an education program for women in our community, reduction of processing time, and convenient home services. The Pap smear screening rate increased from 13.2% to 28.4. The entire processing time was reduced to 20.48 +/- 2.28 minutes. We encourage women of all ages to take Pap smear tests regularly, which would be helpful for the prevention of cervical cancer. PMID- 17340550 TI - [The application of self-efficacy counseling skills to health education in patients with diabetes]. AB - As the incidence of chronic disease increases, empowerment of patients with chronic disease to adopt self-care responsibilities becomes paramount. Self efficacy is a belief in one's ability to perform a task that will lead to the desired outcome. Utilizing self-efficacy counseling skills is an effective way to enhance patients' compliance with self-care activities. The development of such skills can compensate for the lack of traditional health education provided for diabetes patients and plays a significant part in the prevention of acute and chronic complications. Self-efficacy counseling strategies involve: asking questions; focusing on patient's agenda; planning personal treatment schedules; defining problems; setting goals (taking a step-by-step approach); regular follow up and contact with patients; scaling questions; brainstorming solutions; considering past efforts, successes and failures; reassessing confidence; and finally checking behavior changes. Self-efficacy counseling skills can be learned through structured training courses in counseling skills. The aims of this report were twofold: (1) to undertake a literature review on self-efficacy and counseling skills used as the theoretical framework in a health education training program for diabetes; (2) to analyze cases when a counseling guide based upon a self-efficacy framework was used by health counselors to help patients improve their self-confidence and self-care ability. This report reveals it is important to promote the application of counseling skills in nursing interventions in the clinical practice field. PMID- 17340551 TI - [Application of massage therapy in premature infant nursing care]. AB - Massage therapy has been used in the care of premature infants for many years in western countries, and a significant body of research has already shown the effectiveness of massage therapy in significantly increasing body weight, decreasing infant hospital durations, enhancing bone formation, and improving behavior. Key considerations when applying massage therapy on premature infants include gestational age, bodyweight, and physical condition. Nurses can teach parents to administer massage therapy on their premature infants to enhance parent-child attachment and interaction. This article introduces massage therapy principles and methods, the effectiveness of massage therapy in premature infant care, and an approach to teaching parents how to apply massage therapy on their premature infants. Massage therapy can be included in premature infant care programs in the future. PMID- 17340552 TI - [Nursing motivation leadership]. AB - The concept of "patients treated as guests" is emphasized in today's medical service and patient-center nursing care. However, with rapid changes in health insurance and hospital accreditation systems as well as increasing consumer awareness, the nurse manager must both efficiently relieve the working pressure of nurses and motivate them. However, it would be an extreme challenge for nurse managers to build a team in which each member works in a self-fulfilling work environment and achieves a high quality of care. This article presents several theories and techniques that relate to motivation strategies. These strategies can serve as a guide and a reference for nurse managers to inspire teamwork and raise morale. It can be expected that increasing nurse satisfaction, performance, and care quality will decrease turnover and desertion rates. Hopefully, this article will assist nurse managers to become better leaders and to achieve success in providing efficient services and good of nursing care quality. PMID- 17340553 TI - [A nursing experience in a patient with antipsychotics-induced overweight]. AB - The purpose of this article is to describe a nursing experience with a patient with schizophrenia who had antipsychotics-induced overweight. The authors assessed the patient's health condition and provided weight management to reduce her hallucinations as well as her body weight between May 1 and June 10, 2004. Three nursing problems had been identified as follows: disturbed sensory perception, imbalanced nutrition, and ineffective health maintenance. During the nursing process, the authors established a rapport relationship with the patient and her mother, educated them in skills for reducing hallucinations, and designed an individual body weight management program. After the interventions, the patient was able to positively face her illness, effectively use methods to reduce the impact of hallucinations, and successfully lose 5.5 kg. From this perspective, an individual body weight management program can be an effective intervention for nurses to care for this group of patients. PMID- 17340554 TI - [An experience nursing an intravenous drug user(IDU) with AIDS: applying the family stress model]. AB - There is prejudice and fear in society about AIDS, causing the families of AIDS patients to be stigmatized. The number of patients infected with HIV has increased substantially in the past two years as presumably a result of an increase in the sharing of syringes. Intravenous drug users (IDUs) are often isolated from their families, with whom they usually have poor relationships. If they are infected with HIV, it becomes all the more difficult for them to be accepted by their family. The article describes the stress experienced by a family as a result of hospitalization of an IDU with AIDS. The findings from this case report demonstrate three main problems identified from the assessment of Boss's family stress management. These three health-related problems were that the primary caregiver felt exhausted, that communication between parents and children was poor, and that the family's coping ability was compromised. Encouraging positive communication between the client and his mother throughout the period of care enhanced the closeness and harmoniousness of their relationship, as well as the client's sense of security as he approached death. Furthermore, we consulted with social workers in order to facilitate the joint provision of social resources and to assist the family during its crisis. PMID- 17340555 TI - A model of synovial fluid lubricant composition in normal and injured joints. AB - The synovial fluid (SF) of joints normally functions as a biological lubricant, providing low-friction and low-wear properties to articulating cartilage surfaces through the putative contributions of proteoglycan 4 (PRG4), hyaluronic acid (HA), and surface active phospholipids (SAPL). These lubricants are secreted by chondrocytes in articular cartilage and synoviocytes in synovium, and concentrated in the synovial space by the semi-permeable synovial lining. A deficiency in this lubricating system may contribute to the erosion of articulating cartilage surfaces in conditions of arthritis. A quantitative intercompartmental model was developed to predict in vivo SF lubricant concentration in the human knee joint. The model consists of a SF compartment that (a) is lined by cells of appropriate types, (b) is bound by a semi-permeable membrane, and (c) contains factors that regulate lubricant secretion. Lubricant concentration was predicted with different chemical regulators of chondrocyte and synoviocyte secretion, and also with therapeutic interventions of joint lavage and HA injection. The model predicted steady-state lubricant concentrations that were within physiologically observed ranges, and which were markedly altered with chemical regulation. The model also predicted that when starting from a zero lubricant concentration after joint lavage, PRG4 reaches steady-state concentration approximately 10-40 times faster than HA. Additionally, analysis of the clearance rate of HA after therapeutic injection into SF predicted that the majority of HA leaves the joint after approximately 1-2 days. This quantitative intercompartmental model allows integration of biophysical processes to identify both environmental factors and clinical therapies that affect SF lubricant composition in whole joints. PMID- 17340556 TI - Determination of 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid in hair using gas chromatography/tandem mass spectrometry in negative ion chemical ionization mode. PMID- 17340557 TI - Simultaneous determination of gemcitabine, taxol, cyclophosphamide and ifosfamide in wipe samples by high-performance liquid chromatography/tandem mass spectrometry: protocol of validation and uncertainty of measurement. AB - Measurable levels of anticancer agents are still detected on work surfaces in health-care settings. However, application of recent guidelines for the protection of workers' safety and health has resulted in lowered contamination levels. To assess occupational exposure to antineoplastic agents, very sensitive and specific procedures for environmental sampling and analysis are therefore needed. In the present study an assay for simultaneous determination of gemcitabine, taxol, cyclophosphamide, and ifosfamide in wipe samples, using two internal standards (trofosfamide and cephalomannine), was developed and validated by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Solid-phase extraction (SPE) was used for sample concentration and cleanup. The assay was found to be linear up to 1000 ng/wipe, with limits of quantitation of 25.0 ng/wipe for gemcitabine and taxol, and 12.5 ng/wipe for cyclophosphamide and ifosfamide. In order to investigate the effectiveness of the surface sampling, removal efficiency tests were repeated on different types of surfaces. Recovery rates of between 62 and 81% were obtained at two contamination levels (50.0 and 250 ng/100 cm2). Precision and trueness were determined on three different days. The within-day precision was found to be always less than 12.1% for all the analytes. The overall precision, expressed as relative standard deviation (RSD), was always less than 9.4%. Recoveries varying from 75.0 (gemcitabine) to 95.0% (taxol) were obtained at three levels. In order to obtain a quantitative indication of the quality of the result, the overall uncertainty of measurement (UOM) was evaluated according to the EURACHEM/CITAC guide. The relative combined uncertainty was found to be always less than 9.5%. The relative expanded uncertainty was also calculated, at three contamination levels. PMID- 17340558 TI - The impact of impurities in synthetic peptides on the outcome of T-cell stimulation assays. AB - Protein-spanning peptide pools have proven valuable as a screening tool for detecting T-lymphocyte responses against a wide range of proteins. We have used this approach in our search for T cells reactive to the onconeural protein HuD. We found positive responses in only 3 of 127 individuals; however, these were highly unusual in that the same class I HLA alleles and peptides were involved. These T-cell responses were not confirmed when peptides re-synthesized by the same manufacturer with similar and with higher purity levels were used. Our observations indicated that these T-cell responses were not directed against the designed HuD peptides. Here, we report on (i) comparisons of the peptide batches analyzed by matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) that did--and did not--elicit T-cell responses and (ii) a detailed analysis of the various by-products of peptides, irrespective of T cell assay outcome. We found numerous differences between the peptide batches, such as omissions of amino acids in the primary structure of the peptides. Furthermore, some batches revealed strong interactions with calcium ions or contained sulfated peptides. Our data reveal that different batches from the same peptide may contain artefacts that influence the outcome of HLA-restricted T-cell response assays. PMID- 17340559 TI - Evaluating the utility of ion mobility separation in combination with high pressure liquid chromatography/mass spectrometry to facilitate detection of trace impurities in formulated drug products. AB - Many formulated products contain complex polymeric excipients such as polyethylene glycols (PEGs). Such excipients can be readily ionized by electrospray and may be present at very high concentrations, thus making it very difficult to identify trace level impurities such as degradants in samples, even if hyphenated techniques such as liquid chromatography/mass spectrometry (LC/MS) are used. Ion mobility (IM) spectrometry is a very rapid gas-phase separation technique and offers additional separation capability within the LC timeframe. This work investigates the use of an IM separator in combination with high pressure liquid chromatography (HPLC) and MS, to improve the separation of drug related materials from excipients, thus aiding the identification of trace-level impurities in an anti-HIV medication, Combivir. PMID- 17340560 TI - New method for caffeine quantification by planar chromatography coupled with electropray ionization mass spectrometry using stable isotope dilution analysis. AB - A new high-performance thin-layer chromatography/electrospray ionization mass spectrometry (HPTLC/ESI-MS) method for the quantification of caffeine in pharmaceutical and energy drink samples was developed using stable isotope dilution analysis (SIDA). After sample preparation, samples and caffeine standard were applied on silica gel 60 F254 HPTLC plates and over-spotted with caffeine-d3 used for correction of the plunger positioning. After chromatography, densitometric detection was performed by UV absorption at 274 nm. The bands were then eluted by means of a plunger-based extractor into the ESI interface of a single-quadrupole mass spectrometer. For quantification by MS the [M+H]+ ions of caffeine and caffeine-d3 were recorded in the positive ion single ion monitoring (SIM) mode at m/z 195 and 198, respectively. The calibration showed a linear regression with a determination coefficient (R2) of 0.9998. The repeatability (RSD, n=6) in matrix was 0.9990, n = 3). No endogenous interferences were observed in the chromatographic region of interest. The limits of quantification and detection were set at 0.25 and 0.1 microg/mL, respectively. The precision ranged from 0.7 to 13.7% for CAPE, and from 0.4 to 10.4% for FCAPE. Accuracy ranged from -2.8 to 12.4% for CAPE and from -0.6 to 6.8% for FCAPE. The stability was conducted at 4, 25 and 37 degrees C. First-order kinetics was observed for the degradation of CAPE and FCAPE. The energies of activation of CAPE and FCAPE were found to be 17.9 and 20.1 kcal/mol, respectively. Addition of 0.4% of sodium chloride and pH adjustment to 6 prevented their degradation in rat plasma for 24 h and at least one month at -20 degrees C. This study provides useful information for the future pharmacokinetic study of CAPE and FCAPE in rat. PMID- 17340563 TI - Interaction study of aspirin or clopidogrel on pharmacokinetics of donepezil hydrochloride in rats by HPLC-fluorescence detection. AB - The present study aims to investigate the possibility of interaction of aspirin (Asp) or clopidogrel (CG) on donepezil (DP) hydrochloride in rats by HPLC fluorescence detection. The separation of DP was achieved in ca. 13 min without interference of Asp and CG on the chromatogram. DP levels in rat plasma with a single administration of DP (5 mg/kg, i.p., group I) and those with a co administration of Asp (200 mg/kg, p.o., group II or 200 mg/kg, i.p., group III) or CG (5 mg/kg, p.o., group IV) were monitored. The DP concentrations determined in rat plasma ranged from 25.0 to 336.1 ng/mL. Pharmacokinetic parameters for these groups were calculated and compared with one another. No significant difference was observed on the comparison of group I with other groups except for the mean resident time of group IV (p = 0.012). These basic findings may help clinical inference when DP is co-administered with Asp and CG to human. PMID- 17340564 TI - Enantioseparation and determination of 2,2-dimethylcyclopropanecarboxamide and corresponding acid in the bioconversion broth by gas chromatography. AB - A simple and sensitive method employing gas chromatography was developed for the enantioseparation and determination of 2,2-dimethylcyclopropanecarboxamide and its acid in the bioconversion broth. Samples were recovered in high yield by extracting the broth with equal volumes of ethyl acetate twice. Separation of the four enantiomers was performed on a gamma-cyclodextrin based chiral column BGB 175. The effect of column flow rate and temperature on the retention and resolution of the enantiomers was investigated. The proposed method exhibited good linearity, repeatability and precision, and was successfully used to monitor and control the bioconversion process of 2,2-dimethylcyclopropanecarboxamide. PMID- 17340565 TI - High-performance liquid chromatography analysis of curcumin in rat plasma: application to pharmacokinetics of polymeric micellar formulation of curcumin. AB - A simple, rapid and reliable high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of curcumin in rat plasma. Plasma was precipitated with acetonitrile after addition of the internal standard (IS), 4-hydroxybenzophenone. Separation was achieved on a Waters muBondapak C(18) column (3.9 x 300 mm, 5 microm) using acetonitrile (55%) and citric buffer, pH 3.0 (45%) as the mobile phase (flow rate = 1.0 mL/min). The UV detection wavelength was 300 and 428 nm for IS and curcumin, respectively. The extraction efficiencies were 97.08, 95.69 and 94.90% for 50, 200 and 1000 ng/mL of curcumin in rat plasma, respectively. The calibration curve was linear over the range 0.02-1 microg/mL with a correlation coefficient of r(2) > 0.999. The intra- and inter-day coefficients of variation were less than 13%, and mean intra and inter-day errors were less than +/-6% at 50, 200 and 1000 ng/mL of curcumin. This assay was successfully applied to the pharmacokinetic studies of both solubilized curcumin and its polymeric micellar formulation in rats. It was found that polymeric micelles increased the half-life of curcumin 162-fold that of solubilized curcumin and increased the volume of distribution (Vd(ss)) by 70 fold. PMID- 17340566 TI - Liquid chromatography-tandem mass spectrometric assay for the nucleoside reverse transcriptase inhibitor emtricitabine in human plasma. AB - A liquid chromatography-tandem mass spectrometric assay for the determination of the antiretroviral nucleoside emtricitabine in human plasma was developed and validated using a simple sample pre-treatment procedure. After addition of 5' deoxy-5-fluorocytidine as the internal standard and protein precipitation with acetonitrile, the supernatant was directly injected in the isocratic chromatographic system using a polar embedded reversed-phase column and formic acid in water-methanol as the eluent. The eluate was completely led into an electrospray interface with positive ionization and the analytes were quantified using triple quadrupole mass spectrometry. The assay was validated in the range 5 5000 ng/mL. Intra-day precisions were or =3 genitourinary (GU) and gastrointestinal (GI) toxicity after treatment with external-beam radiotherapy and brachytherapy in a multiinstitutional, cooperative group setting. METHODS: All eligible patients received external-beam radiotherapy (45 Gray [Gy] in 25 fractions) followed 2 to 6 weeks later by an interstitial implant using iodine-125 to deliver an additional 108 Gy. BR was defined in 2 ways: according to the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Definition (ACD) and according to the Phoenix definition (PD) (prostate-specific antigen nadir +2 ng/mL). The Radiation Therapy Oncology Group(RTOG)/European Organization for Research and Treatment of Cancer late radiation morbidity scoring system was used to grade all toxicity. RESULTS: One hundred thirty-eight patients were enrolled, and 130 were eligible for the current analysis. The median follow-up for surviving patients was 49 months (range, 20-60 months). The 48-month estimate of late grade > or =3 GU/GI toxicity was 15% (95% confidence interval [95% CI], 8-21%), and the 48-month estimate of BR was 19% (95% CI, 12-26%) and 14% (95% CI, 8-20%) according to the ACD and PD, respectively. CONCLUSIONS: The morbidity observed in this multiinstitutional, cooperative group study was slightly higher than that reported in recent RTOG studies using brachytherapy alone or high-dose external-beam radiotherapy. The BR rate observed in this report was similar to that observed with high-dose external beam radiotherapy alone in similar patients. PMID- 17340593 TI - The formation of the Spanish Rheumatology Nursing Society. PMID- 17340592 TI - Elevated expression of vascular endothelial growth factor correlates with increased angiogenesis and decreased progression-free survival among patients with low-grade neuroendocrine tumors. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) is a critical proangiogenic factor in solid tumors. However, its expression and role in human neuroendocrine tumor development and progression remains unclear. METHODS: Using immunohistochemistry, VEGF and Sp1 expression patterns were investigated in 50 cases of human gastrointestinal neuroendocrine tumor having various clinicopathologic characteristics. RESULTS: It was found that strong VEGF expression was detected in tumor cells, whereas no or very weak VEGF expression was detected in stromal cells surrounding or within the tumors. The levels of VEGF expression directly correlated with the expression levels of Sp1 and microvessel density. Strong, weak, and negative VEGF expression was observed in 32%, 54%, and 14% of cases, respectively. Compared with the group with negative VEGF expression, VEGF (weak/strong) expression was associated with metastasis (14% versus 58%; P = .03). The median progression-free survival (PFS) durations of patients with strong and weak VEGF expression were 29 months and 81 months, respectively. With a median follow-up duration of 50 months, the median PFS duration for the group with negative VEGF expression has not been reached. Compared with the log-rank test, VEGF expression was associated with poor PFS (P = .02). Using in vitro and in vivo models, human carcinoid cell lines were treated with bevacizumab, a monoclonal antibody targeting VEGF. Bevacizumab did not inhibit the growth of carcinoid cells in vitro but significantly reduced tumor angiogenesis and impaired tumor growth in animals. CONCLUSIONS: The data suggest that overexpression of VEGF promotes the growth of human neuroendocrine tumors in part through up-regulation of angiogenesis. PMID- 17340594 TI - Influence of body mass index on prostate-specific antigen failure after androgen suppression and radiation therapy for localized prostate cancer. AB - BACKGROUND: Increasing body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure after radical prostatectomy. Whether BMI is associated with time to PSA failure was investigated in men treated with androgen suppression therapy (AST) and radiation therapy (RT) for clinically localized prostate cancer. METHODS: The observational prospective cohort study consisted of 102 men with clinically localized prostate cancer who received 70 Gy RT with 6 months of AST on a single arm of a randomized trial between December 1995 and April 2001. Height and weight data were available at baseline for 99 (97%) of the men, from which BMI was calculated. Adjusting for age (continuous) and known prognostic factors including PSA level (continuous), Gleason score, and T-category, Cox regression analyses were performed to analyze whether BMI (continuous) was associated with time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits). RESULTS: Median age and median BMI (interquartile range [IQR]) at baseline was 72 (69.1-74.7) years and 27.4 (24.8-30.7) kg/m,(2) respectively. In addition to an increasing PSA level (P = .006) and Gleason 8-10 cancer (P = .024), after a median follow-up (IQR) of 6.9 (5.6-8.5) years, an increasing BMI was also significantly associated with a shorter time to PSA failure (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.01-1.19; P = .026) after RT and AST. CONCLUSIONS: After adjusting for known prognostic factors, baseline BMI is significantly associated with time to PSA failure after RT and AST for men with clinically localized prostate cancer. Further study is warranted to assess the impact of an increasing BMI after AST administration on PSA failure, prostate cancer-specific, and all cause mortality. PMID- 17340595 TI - Sleep disruption frequency in rheumatoid arthritis: perceived stress predicts poor outcome over one year. AB - BACKGROUND: Sleep is an important daily process that can be disrupted by chronic illnesses including rheumatoid arthritis (RA). AIMS: We tested whether demographic, medical and psychological factors act as predictors of change in frequency of sleep disruption associated with RA. METHODS: A cohort of 129 White British people with RA (mean duration of RA 7.19 years; mean age 55.40 years; 75% women) was followed for one year. Self-report questionnaires were employed to record demographic information and assess participants' sleep disruption (on a 4 point frequency scale), morning stiffness (duration), pain and fatigue (visual analogue scales), impact of disability, anxiety, depression, stress, coping, illness perceptions and self-efficacy. Hospital notes were reviewed for duration of RA, antidepressant use and comorbidity. RESULTS: Participants were split into those with sleep disruption that was consistently infrequent or decreasing in frequency (n = 56; 43%) and those with sleep disruption that was consistently frequent or increasing in frequency (n = 73; 57%). Results of a logistic regression demonstrated that greater perceived stress at baseline predicted sleep disruption that was consistently frequent or increasing in frequency over the year. Change in sleep disruption frequency was not predicted by any other assessed variable. Perceived stress at the end of the year was not predicted by change in frequency of sleep disruption. CONCLUSIONS: Self-reported frequency of sleep disruption among people with RA relates to perceived stress. Psychoeducational programmes that help people with RA manage their stress may be a non-pharmacological method of improving sleep quality and therefore merits testing in specific interventional studies. PMID- 17340596 TI - The application of multilevel modelling to dental caries data. AB - Clinical studies of dental caries experience generate multiple outcome data for each participant, with information collected for each individual tooth surface. This paper investigates multilevel modelling as a method of analysis for dental caries data, allowing for full use of the data collected at surface level. Data from a clinical trial of a caries preventive agent in adolescents are modelled. The effect of tooth position within the mouth on the development of dental caries is investigated, with the results showing the importance of differentiating between the upper and lower arches, when modelling the probabilities of caries developing on teeth. Calculation of the intracluster correlation using the threshold model is suggested for use in multilevel logistic regression modelling of caries data. This model, which assumes that a dichotomous outcome is based on an underlying continuous variable with a threshold point where the outcome changes from zero to one, is identified to be appropriate for the analysis of caries which is a continuous process, but is only identified as present in a clinical trial when it has reached a certain level of severity. PMID- 17340597 TI - Current issues in non-inferiority trials. AB - Non-inferiority (NI) trials enable a direct comparison of the relative benefit-to risk profiles of an experimental intervention and a standard-of-care regimen. When the standard has clinical efficacy of substantial magnitude that is precisely estimated ideally using data from multiple adequate and well-controlled trials, with such estimates being relevant to the setting of the NI trial, then the NI trial can provide the scientific and regulatory evidence required to reliably assess the efficacy of the new intervention. In clinical practice, considerable uncertainty remains regarding when such trials should be conducted, how they should be designed, what standards for quality of trial conduct must be achieved, and how results should be interpreted. Recent examples will be considered to provide important insights and to highlight some of the challenges that remain to be adequately addressed regarding the use of the NI approach for the evaluation of new interventions. 'Imputed placebo' and 'margin'-based approaches to NI trial design will be considered, as well as the risk of 'bio creep' with repeated NI trials, use of NI trials when determining whether excess safety risks can be ruled out, higher standards regarding quality of study conduct required with NI trials, and the myth that NI trials always require huge sample sizes. PMID- 17340598 TI - Hierarchical models for ROC curve summary measures: design and analysis of multi reader, multi-modality studies of medical tests. AB - Comparative studies of the accuracy of diagnostic tests often involve designs according to which each study participant is examined by two or more of the tests and the diagnostic examinations are interpreted by several readers. Tests are then compared on the basis of a summary index, such as the (full or partial) area under the receiver operating characteristic (ROC) curve, averaged over the population of readers. The design and analysis of such studies naturally need to take into account the correlated nature of the diagnostic test results and interpretations. In this paper, we describe the use of hierarchical modelling for ROC summary measures derived from multi-reader, multi-modality studies. The models allow the variance of the estimates to depend on the actual value of the index and account for the correlation in the data both explicitly via parameters and implicitly via the hierarchical structure. After showing how the hierarchical models can be employed in the analysis of data from multi-reader, multi-modality studies, we discuss the design of such studies using the simulation-based, Bayesian design approach of Wang and Gelfand (Stat. Sci. 2002; 17(2):193-208). The methodology is illustrated via the analysis of data from a study conducted to evaluate a computer-aided diagnosis tool for screen film mammography and via the development of design considerations for a multi-reader study comparing display modes for digital mammography. The hierarchical model methodology described in this paper is also applicable to the meta-analysis of ROC studies. PMID- 17340599 TI - Gentamicin-loaded bioresorbable films for prevention of bacterial infections associated with orthopedic implants. AB - Adhesion of bacteria to biomaterials and the ability of many microorganisms to form biofilms on foreign bodies are well-established as major contributors to the pathogenesis of implant-associated infections. Treatment of bone infection remains problematic, due to the difficulty of systemically administered antibiotics to locally penetrate bone. The current research addresses this issue by focusing on the development and study of novel gentamicin-loaded bioresorbable films designed to serve as "coatings" for fracture fixation devices and prevent implant-associated infections. Poly(L-lactic acid) and poly (D,L-lactic-co glycolic acid) films containing gentamicin were developed through solution processing. The effects of polymer type, drug content, and processing conditions on the drug release profile were studied with respect to film morphology. The examined films generally exhibited a burst effect followed by a moderate approximately constant rate of release. The drug contents in the surrounding medium exceeded the required minimal effective concentration. Various gentamicin concentrations that were released from the films with time exhibited efficacy against bacterial species known to be involved in orthopedic infections. The developed systems can be applied on the surface of any metallic or polymeric fracture fixation device, and may therefore comprise a significant contribution to the field of orthopedic implants. PMID- 17340600 TI - Osteoblast response to fluid induced shear depends on substrate microarchitecture and varies with time. AB - Osteoblasts are exposed to fluid shear in vivo but the effects are not well understood, particularly how substrate properties or length of exposure modify the response. Short exposure (1 h) to shear reduces the stimulatory effect of micron-scale surface structure on osteoblast differentiation, but the effects of longer term exposures are not known. To test the hypothesis that substrate dependent responses of osteoblasts to shear depend on the length of exposure to fluid flow, MG63 osteoblasts were grown on tissue culture glass, which has an average roughness (Ra) < 0.2 microm; machined Ti disks (PT, Ra < 0.6 microm); Ti disks with a complex microarchitecture [sand blasted acid etched (SLA), Ra = 4-5 microm); and Ti plasma-sprayed surfaces [Ti via plasma spray (TPS), Ra = 7 microm]. Confluent cultures were exposed to pulsatile flow at shear forces of 0, 1, and 14 dynes/cm(2) for 0, 6, 12, and 24 h. Shear reduced cell number on all surfaces, with greatest effects on TPS. Shear had no effect on alkaline phosphatase on smooth surfaces but increased enzyme activity on SLA and TPS in a time-dependent manner. Its effects on osteocalcin, TGF-beta1, and PGE(2) in the conditioned media were greatest on these surfaces as well. Responses to fluid induced shear were blocked by the general Cox inhibitor indomethacin and the Cox 2 inhibitor meloxicam, indicating that response to shear is mediated by prostaglandin produced via a Cox-2 dependent mechanism. These results show that the effects of fluid induced shear change with time and are substrate dependent, suggesting that substrate microarchitecture regulates the osteoblast phenotype and effects of shear are determined by the maturation state of the responding population. PMID- 17340601 TI - A prospective test of anxiety sensitivity as a moderator of the relation between gender and posttraumatic symptom maintenance among high anxiety sensitive young adults. AB - The primary aim of this study was to evaluate the individual and combined influence of anxiety sensitivity (AS) and gender on the longitudinal prediction of posttraumatic symptoms. A large nonclinical sample of young adults (n=404) was prospectively followed over approximately 18 months. The primary findings indicated that gender and AS were uniquely associated with posttraumatic symptom levels during the follow-up period. Moreover, AS appeared more strongly (positively) related to posttraumatic stress symptoms during the follow-up period among females than males. These data provide novel prospective evidence regarding the interplay of relatively well-established risk factors implicated in the maintenance of posttraumatic stress symptoms. PMID- 17340602 TI - Theoretical calculations: can Gibbs free energy for intermolecular complexes be predicted efficiently and accurately? AB - The theoretical study has been performed to refine the procedure for calculations of Gibbs free energy with a relative accuracy of less than 1 kcal/mol. Three benchmark intermolecular complexes are examined via several quantum-chemical methods, including the second-order Moller-Plesset perturbation (MP2), coupled cluster (CCSD(T)), and density functional (BLYP, B3LYP) theories augmented by Dunnings correlation-consistent basis sets. The effects of electron correlation, basis set size, and anharmonicity are systematically analyzed, and the results are compared with available experimental data. The results of the calculations suggest that experimental accuracy can be reached only by extrapolation of MP2 and CCSD(T) total energies to the complete basis set. The contribution of anharmonicity to the zero point energy and TDeltaSint values is fairly small. The new, economic way to reach chemical accuracy in the calculations of the thermodynamic parameters of intermolecular interactions is proposed. In addition, interaction energy (De) and free energy change (DeltaA) for considered species have been evaluated by Carr-Parrinello molecular dynamics (CPMD) simulations and static BLYP-plane wave calculations. The free energy change along the reaction paths were determined by the thermodynamic integration/"Blue Moon Ensemble" technique. Comparison between obtained values, and available experimental and conventional ab initio results has been made. We found that the accuracy of CPMD simulations is affected by several factors, including statistical uncertainty and convergence of constrained forces (TD integration), and the nature of DFT (density functional theory) functional. The results show that CPMD technique is capable of reproducing interaction and free energy with an accuracy of 1 kcal/mol and 2-3 kcal/mol respectively. PMID- 17340603 TI - Associations between HPA axis functioning and level of anxiety in children and adolescents with an anxiety disorder. AB - The hypothalamus-pituitary-adrenal (HPA) axis becomes active in response to stress. Hence, increased levels of anxiety in children and adolescents may be associated with changes in HPA-axis functioning. The aim of this study was to test if level of anxiety or specific anxiety disorders were associated with basal HPA axis activity in children and adolescents with an anxiety disorder. In 99 8- to 16-year-olds with an anxiety disorder, basal cortisol levels were assessed. It was tested if (1) cortisol levels correlated with the level of self-reported anxiety and (2) if cortisol levels were different for individuals with different anxiety disorders. In girls, low levels of anxiety were associated with a stronger rise in early morning cortisol concentrations. In both boys and girls, harm avoidance predicted low cortisol concentrations after awakening. Separation anxiety and physical anxiety symptoms predicted cortisol concentrations at noon. Differences between individuals with different anxiety disorders were not found. More research is needed regarding mechanisms that explain the associations that were found, and to investigate if treatment may influence HPA axis functioning in children and adolescents with an anxiety disorder. PMID- 17340604 TI - DFT and ab initio calculations on two reactions between hydrogen atoms and the fire suppressants 2-H heptafluoropropane and CF3Br. AB - Reaction enthalpies and barrier heights of the reactions CF3Br+H-->CF3+HBr {reaction (1)} and CF3CHFCF3+H-->CF3CFCF3+H2 {reaction (2)} have been calculated at the near state-of-the-art ab initio level, and also by employing the B3LYP, BH&HLYP, BB1K, MPW1K, MPWB1K and TPSS1KCIS functionals. In addition, the integrated molecular orbital+molecular orbital (IMOMO) method has been used to study reaction (2). The ab initio benchmark values of the reaction enthalpy (298 K) and barrier height (0 K) of reaction (2) are reported for the first time { (0.7+/-0.7) and 13.3+/-0.5 kcal/mole respectively}. When density functional theory (DFT) results are compared with ab initio benchmarks for both reactions (1) and (2), the MPWB1K functional is found to have the best performance of the six functionals used. The IMOMO method with the RCCSD/aug-cc-pVTZ and/or RCCSD(T)/aug-cc-pVTZ levels, as the high levels of calculation on the model system, gives reaction enthalpies and barrier heights of reaction (2), which agree with ab initio benchmark values to within 1 kcal/mole. Computed key geometrical parameters and imaginary vibrational frequencies of the transition state structures of reactions (1) and (2) obtained at different levels of calculation are compared. The magnitudes of the computed imaginary vibrational frequencies of the transition states of both reactions considered are found to be very sensitive to the levels of calculation used to obtain them. The heat of formation (298 K) of CF3CFCF3 calculated at the near state-of-the-art level has a value of -(318+/-3) kcal/mole. PMID- 17340605 TI - Computational tool to model the packing of polycyclic chains: structural analysis of amorphous polythiophene. AB - A very efficient computational procedure, which was previously developed to generate and relax atomistic models of linear and comb-like amorphous polymers, has been adapted to model the amorphous phase of polycyclic systems. The strategy, which is a based in a generation algorithm that eliminates the torsion strain and a simple Monte Carlo Metropolis method to relax the generated structures, has been used to predict the density of amorphous polythiophene by combining NVT and NPT simulations. The theoretical value is in the excellent agreement with the experimental one, the former being overestimated by only 3-5%. Next, the molecular conformation and the packing of the rings were studied in detail. Interestingly, the amorphous phase of polythiophene can be described as a packing of elongated molecular chains more or less aligned in the same direction, in which the thiophene rings close in the space but belonging to different chains tend to adopt approximate parallel or antiparallel displaced pi-stacked arrangements. PMID- 17340606 TI - Change in a protein's electronic structure induced by an explicit solvent: an ab initio fragment molecular orbital study of ubiquitin. AB - The effect of solvation on the electronic structure of the ubiquitin protein was analyzed using the ab initio fragment molecular orbital (FMO) method. FMO calculations were performed for the protein in vacuo, and the protein was immersed in an explicit solvent shell as thick as 12 A at the HF or MP2 level by using the 6-31G* basis set. The protein's physical properties examined were the net charge, the dipole moment, the internal energy, and the solvent interaction energy. Comparison of the computational results revealed the following changes in the protein upon solvation. First, the positively charged amino acid residues on the protein surface drew electrons from the solvent, while the negatively charged ones transfer electrons to the solvent. Second, the dipole moment of the protein was enhanced as a result of the polarization. Third, the internal energy of the protein was destabilized, but the destabilization was more than compensated for by the generation of a favorable protein-solvent interaction. Finally, the energetic changes were elicited both by the electron correlation effect of the first solvent shell and by the electrostatic effect of more distant solvent molecules. These findings were consistent with the picture of the solvated protein being a polarizable molecule dissolved in a dielectric media. PMID- 17340607 TI - Comparison of the numerical stability of methods for anharmonic calculations of vibrational molecular energies. AB - On model examples, we compare the performance of the vibrational self-consistent field, variational, and four perturbational schemes used for computations of vibrational energies of semi-rigid molecules, with emphasis on the numerical stability. Although the accuracy of the energies is primarily dependent on the quality of the potential energy surface, approximate approaches to the anharmonic vibrational problem often do not converge to the same results due to the approximations involved. For furan, the sensitivity to variations of the anharmonic potential was systematically investigated by adding random noise to the cubic and quartic constants. The self-consistent field methods proved to be the most resistant to the potential variations. The second order perturbational techniques are sensitive to random degeneracies and provided the least stable results. However, their stability could be significantly improved by a simple generalization of the perturbational formula. The variational configuration interaction is practically limited by the size of the matrix that can be diagonalized for larger molecules; however, relatively fewer states need to be involved than for smaller ones, in favor of the computing. PMID- 17340608 TI - Excited state properties, fluorescence energies, and lifetime of a poly(fluorene pyridine) copolymer, based on TD-DFT investigation. AB - The structural and electronic properties of the fluorene-pyridine copolymer (FPy)(n), (n = 1-4) were investigated theoretically by means of quantum mechanical calculations based on density functional theory (DFT) and time dependent DFT (TD-DFT) using the B3LYP functional. Geometry optimizations of these oligomers were performed for the ground state and the lowest excited state. It was found that (FPy)(n) is nonplanar in its ground state, whereas a more pronounced trend toward planarity is observed in the S(1) state. Absorption and fluorescence energies have been extrapolated to infinite chain length making use of their good linearity with respect to 1/n. An extrapolated value of 2.64 eV is obtained for vertical excitation energy. The S(1)<--S(0) electronic excitation is characterized as a highest occupied molecular orbital to lowest unoccupied molecular orbital transition and is dominating in terms of oscillator strength. Fluorescence energies and radiative lifetime were calculated as well. The obtained results indicate that the fluorescence energy and radiative lifetime of (FPy)(n) are 2.16 eV and 0.38 ns, respectively. The decrease of fluorescence energy and radiative lifetime with the increase in the chain length is discussed. PMID- 17340609 TI - Features of the offensive subtype of Taijin-Kyofu-Sho in US and Korean patients with DSM-IV social anxiety disorder. AB - Taijin-Kyofu-Sho (TKS), an East Asian syndrome of interpersonal fear and avoidance, that has been considered culture-bound, overlaps with social anxiety disorder to an unknown extent. The offensive subtype of TKS is characterized by two features considered atypical of social anxiety disorder: the belief that one displays physical defects and/or socially inappropriate behaviors (offensive TKS symptoms) and fear of offending others (allocentric focus), but no studies have systematically evaluated these two features in patients with social anxiety disorder. The purpose of this study was to assess offensive TKS symptoms and allocentric focus of fear in US (n = 181) and Korean (n = 64) patients with DSM IV social anxiety disorder, using the newly developed TKS Questionnaire. Seventy five percent of patients with social anxiety disorder in the US and Korea endorsed at least one of the five offensive TKS symptoms surveyed. The severity of features of offensive TKS was significantly associated with severity of social anxiety symptoms, depressive symptoms, and disability in both samples. These results suggest that features of the offensive subtype of TKS are not uncommon among US patients with social anxiety disorder and may not be as culturally specific as previously believed. They also suggest that Western clinicians should assess patients with social anxiety for features of offensive TKS, and they support further consideration of integrating TKS features into conceptualizations of social anxiety disorder. PMID- 17340610 TI - Aripiprazole augmentation of incomplete treatment response in an adolescent male with obsessive-compulsive disorder. AB - We report the case of adolescent male with obsessive-compulsive disorder (OCD) who had an incomplete response to combined cognitive-behavioral therapy (CBT) and sertraline before successful augmentation of CBT with aripiprazole. Standardized assessments indicated significant reductions in OCD symptomatology associated with both initial treatment and aripiprazole augmentation. This case suggests that aripiprazole may have utility as an augmenting agent of CBT in adolescents with OCD and underscores the need for conducting controlled studies to test this hypothesis. PMID- 17340611 TI - Potential work-related exposures to bloodborne pathogens by industry and occupation in the United States Part II: A telephone interview study. AB - BACKGROUND: The companion surveillance portion of this study [Chen and Jenkins, 2007] reported the frequency and rate of potential work-related exposures to bloodborne pathogens (BBP) treated in emergency departments (EDs) by industry and occupation, but it lacks details on the circumstances of the exposure and other relevant issues such as BBP safety training, use of personal protective equipment (PPE) or safety needles, or reasons for seeking treatment in a hospital ED. METHODS: Telephone interviews were conducted with workers who had been treated in EDs for potential work-related exposures to BBP in 2000-2002. Respondents were drawn from the National Electronic Injury Surveillance System. RESULTS: Of the 593 interviews, 382 were from hospitals, 51 were from emergency medical service/firefighting (EMS/FF), 86 were from non-hospital healthcare settings (e.g., nursing homes, doctors' offices, home healthcare providers, etc.), 22 were from law enforcement (including police and correctional facilities), and 52 were from other non-healthcare settings (i.e., schools, hotels, and restaurants). Needlestick/sharps injuries were the primary source of exposure in hospitals and non-hospital healthcare settings. Skin and mucous membrane was the primary route of exposure in EMS/FF. Human bites accounted for a significant portion of the exposures in law enforcement and other non-healthcare settings. In general, workers from non-hospital settings were less likely to use PPE, to have BBP safety training, to be aware of the BBP standards and exposure treatment procedures, and to report or seek treatment for a work-related exposure compared to hospital workers. CONCLUSIONS: This study suggests that each industry group has unique needs that should be addressed. PMID- 17340612 TI - Cognitive behavioral treatment groups for people with chronic depression in Hong Kong: a randomized wait-list control design. AB - This study examined the effectiveness of a cognitive-behavioral treatment (CBT) group for Chinese people with depression in Hong Kong. Ninety-six subjects with depression were randomly assigned to CBT and control groups. After 10 weeks of treatment, participants in the CBT group had significantly fewer symptoms of depression, dysfunctional rules, and negative emotions, and significantly more adaptive coping skills when compared to the participants in the control group. Effect size statistics showed medium to large differences in symptoms of depression, coping skills, dysfunctional rules, and assumptions and negative emotions between the participants of the two groups (Cohen's d, between 0.50 and 0.88, except for positive emotions). Forty percent of the participants in the experimental group achieved a clinically significant level [reliable change index (RC)>1.96] of improvement. Lastly, the results of a multiple regression analysis provided some evidence of a linkage between cognition and depression among the participants in the experimental group. The design and content of the CBT groups, which aimed at facilitating the understanding and modification of automatic thoughts and dysfunctional rules, and of negative and positive coping skills among the participants, might have contributed to the initial positive results. PMID- 17340613 TI - TIMP-1 regulates cell proliferation by interacting with the ninth zinc finger domain of PLZF. AB - The tissue inhibitors of metalloproteinases (TIMPs) are multifunctional proteins that specifically inhibit matrix metalloproteinases (MMPs) and regulate extracellular matrix (ECM) turnover and tissue remodeling. This is directed by forming tightly bound inhibitory complexes with MMPs. Recent years have revealed important differences of various biological activities between TIMP families but molecular mechanisms are not clear. To define the molecular mechanisms of TIMP-1 dependent biological processes, we used TIMP-1 as bait in a yeast two-hybrid screen, along with a human ovary cDNA library. Further characterization revealed the ninth zinc finger domain as an interacting domain of the promyelocytic leukemia zinc finger protein (PLZF). Interaction of PLZF with TIMP-1 in mammalian cells was also confirmed by co-immunoprecipitation and with in vitro binding assays. We investigated whether TIMP-1-mediated anti-apoptotic activity could promote the growth of ovarian cancer in an experimental model system. TIMP-1 treatment was found to be more effective at increasing ovarian cancer growth when compared with PLZF in parallel experiments. Subsequently, the efficacy of a combined treatment with TIMP-1 and PLZF was investigated. In the presence of both of these proteins, TIMP-1 significantly reduced apoptosis induced by PLZF in cervical carcinoma cells. These combined results indicate that TIMP-1 functions as an anti-activator of the transcriptional repressive activity of PLZF. PMID- 17340614 TI - A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. AB - Transforming growth factor-beta (TGF-beta) is an important growth inhibitor of epithelial cells, and insensitivity to this cytokine results in uncontrolled cell proliferation and can contribute to tumorigenesis. Smad2 and Smad3 are direct mediators of TGF-beta signaling, however little is known about the selective activation of Smad2 versus Smad3. The Smad2 and Smad3 knockout mouse phenotypes and studies comparing Smad2 and Smad3 activation of TGF-beta target genes, suggest that Smad2 and Smad3 have distinct roles in TGF-beta signaling. The observation that TGF-beta inhibits proliferation of Smad3-null mammary gland epithelial cells, whereas Smad3 deficient fibroblasts are only partially growth inhibited, suggests that Smad3 has a different role in epithelial cells and fibroblasts. Herein, the current understanding of Smad2 and Smad3-mediated TGF beta signaling and their relative roles are discussed, in addition to potential mechanisms for the selective activation of Smad2 versus Smad3. Since alterations in the TGF-beta signaling pathway play an important role in promoting tumorigenesis and cancer progression, methods for therapeutic targeting of the TGF-beta signaling pathway are being pursued. Determining how Smad2 or Smad3 differentially regulate the TGF-beta response may translate into developing more effective strategies for cancer therapy. PMID- 17340615 TI - Social anxiety and insomnia: the mediating role of depressive symptoms. AB - Anxiety is commonly associated with insomnia. Given that social anxiety disorder is one of the most prevalent anxiety disorders, socially anxious individuals may be particularly vulnerable to insomnia. However, there is currently very little empirical work on this relationship. This study used bivariate correlations to examine whether social anxiety was related to insomnia in an undergraduate sample (n=176) using the Social Interaction Anxiety Scale and the Insomnia Severity Index. Further, we utilized responses from the Beck Depression Inventory to investigate the role of depressive symptoms in the association between social anxiety and insomnia. Hierarchical linear regressions were used to examine the moderational and mediational role of depressive symptoms in the link between social anxiety and insomnia. To increase generalizability to clinical samples, analyses were repeated on a subset of the sample with clinically significant social anxiety symptoms (n=23) compared to a matched control group (n=23). Consistent with expectation, social anxiety was associated with increased insomnia symptoms. Specifically, social anxiety was correlated with sleep dissatisfaction, sleep-related functional impairment, perception of a sleep problem to others, and distress about sleep problems. Importantly, depressive symptoms mediated the relationship between social anxiety and insomnia, thereby at least partially accounting for insomnia among socially anxious individuals. Our data support the contention that social anxiety is associated with insomnia and suggest that depression may play a vital role in this co-occurrence. PMID- 17340616 TI - Annexin 1: differential expression in tumor and mast cells in human larynx cancer. AB - Annexin 1 protein (ANXA1) expression was evaluated in tumor and mast cells in human larynx cancer and control epithelium. The effect of the exogenous ANXA1 (peptide Ac 2-26) was also examined during the cellular growth of the Hep-2 human larynx epidermoid carcinoma cell line. This peptide inhibited the proliferation of the Hep-2 cells within 144 hr. In surgical tissue specimens from 20 patients with larynx cancer, ultrastructural immunocytochemistry analysis showed in vivo down-regulation of ANXA1 expression in the tumor and increased in mast cells and Hep-2 cells treated with peptide Ac2-26. Combined in vivo and in vitro analysis demonstrated that ANXA1 plays a regulatory role in laryngeal cancer cell growth. We believe that a better understanding of the regulatory mechanisms of ANXA1 in tumor and mast cells may lead to future biological targets for the therapeutic intervention of human larynx cancer. PMID- 17340617 TI - Evidence for the existence of satellite DNA-containing connection between metaphase chromosomes. AB - Physical connections between mitotic chromosomes have been reported previously. It was assumed that the interchromosome connection was based on the DNA-protein thread. However, the data about DNA sequences and protein component in the thread is fragmentary. We demonstrated on the mouse cultured cell line and prematurely condensed chromosomes that: (a) all four mouse satellite DNA fragments (major and minor satellite, mouse satellite 3 (MS3) and mouse satellite 4 (MS4)) were involved in the thread formation; (b) MS4 was involved in the thread to the least extent among all the other fragments; (c) telomere was never a member of the thread; (d) the thread was synthesized at a late G(2) phase; (e) RNA helicase p68 and CENP-B were among the protein components of the interchromosome connection. It was shown by FACS analysis that in mouse and human cell lines: (1) the flow karyotype spectrums were never free from chromosome aggregates; (2) chromosome association did not depend on the chromosome length and each chromosome was free to associate with the other. PMID- 17340618 TI - Antiproliferative activity of CCN3: involvement of the C-terminal module and post translational regulation. AB - Previous work had suggested that recombinant CCN3 was partially inhibiting cell proliferation. Here we show that native CCN3 protein secreted into the conditioned medium of glioma transfected cells indeed induces a reduction in cell proliferation. Large amounts of CCN3 are shown to accumulate both cytoplasmically and extracellularly as cells reach high density, therefore highlighting new aspects on how cell growth may be regulated by CCN proteins. Evidence is presented establishing that the amount of CCN3 secreted into cell culture medium is regulated by post-translational proteolysis. As a consequence, the production of CCN3 varies throughout the cell cycle and CCN3 accumulates at the G2/M transition of the cycle. We also show that CCN3-induced inhibition of cell growth can be partially reversed by specific antibodies raised against a C-terminal peptide of CCN3. The use of several clones expressing various portions of CCN3 established that the CT module of CCN3 is sufficient to induce cell growth inhibition. PMID- 17340619 TI - Identification of a monopartite sequence in PU.1 essential for nuclear import, DNA-binding and transcription of myeloid-specific genes. AB - The Ets transcription factor PU.1 is an essential regulator of normal hematopoiesis, especially within the myeloid lineage. As such, endogenous PU.1 predominantly localizes to the nucleus of mammalian cells to facilitate gene regulation. However, to date, little is known regarding the mechanisms of PU.1 nuclear transport. We found, using HeLa and RAW 264.7 macrophage cells, that PU.1 enters the nucleus via passive diffusion and active transport. The latter can be facilitated by: (i) the classical pathway requiring importin alpha and beta; (ii) the non-classical pathway requiring only importin beta; or (iii) direct interaction with nucleoporins. A group of six positively charged lysine or arginine residues within the Ets DNA-binding domain was determined to be crucial in active nuclear import. These residues directly interact with importin beta to facilitate a predominantly non-classical import pathway. Furthermore, luciferase reporter assays demonstrated that these same six amino acids are crucial for PU.1 mediated transcriptional activation of myeloid-specific genes. Indeed, these residues may represent a consensus sequence vital for nuclear import, DNA-binding and transcriptional activity of Ets family members. By identifying and characterizing the mechanisms of PU.1 nuclear import and the specific amino acids involved, this report may provide insights into the molecular basis of diseases. PMID- 17340620 TI - Angiotensin converting enzyme 2 is primarily epithelial and is developmentally regulated in the mouse lung. AB - Angiotensin converting enzyme (ACE) 2 is a carboxypeptidase that shares 42% amino acid homology with ACE. Little is known about the regulation or pattern of expression of ACE2 in the mouse lung, including its definitive cellular distribution or developmental changes. Based on Northern blot and RT-PCR data, we report two distinct transcripts of ACE2 in the mouse lung and kidney and describe a 5' exon 1a previously unidentified in the mouse. Western blots show multiple isoforms of ACE2, with predominance of a 75-80 kDa protein in the mouse lung versus a 120 kDa form in the mouse kidney. Immunohistochemistry localizes ACE2 protein to Clara cells, type II cells, and endothelium and smooth muscle of small and medium vessels in the mouse lung. ACE2 mRNA levels peak at embryonic day 18.5 in the mouse lung, and immunostaining demonstrates protein primarily in the bronchiolar epithelium at that developmental time point. In murine cell lines ACE2 is strongly expressed in the Clara cell line mtCC, as opposed to the low mRNA expression detected in E10 (type I-like alveolar epithelial cell line), MLE 15 (type II alveolar epithelial cell line), MFLM-4 (fetal pulmonary vasculature cell line), and BUMPT-7 (renal proximal tubule cell line). In summary, murine pulmonary ACE2 appears to be primarily epithelial, is developmentally regulated, and has two transcripts that include a previously undescribed exon. PMID- 17340621 TI - Bystander killing of breast cancer MCF-7 cells by MDA-MB-231 cells exposed to 5 fluorouracil is mediated via Fas. AB - The major drawback with cancer therapy is the development of resistant cells within tumors due to their heterogeneous nature and due to inadequate drug delivery during chemotherapy. Therefore, the propagation of injury ("bystander effect" (BE)) from directly damaged cells to other cells may have great implications in cancer chemotherapy. The general advantage of the bystander cell killing phenomenon is the large therapeutic index that can be achieved. Experiments suggest that this phenomenon is detected in radiation therapy as well as in gene therapy in conjunction with chemotherapy. In the present study, we developed an original in vitro model dedicated to the exploration of bystander cytotoxicity induced during breast carcinoma chemotherapy. In brief, we investigated this perpetuation of injury on untreated bystander MCF-7 breast cancer cells which were coplated with 5-fluorouracil (5-FU)-treated MDA-MB-231 breast cancer cells. To achieve this goal, a specific in vitro coculture model which involved mixing of aggressive MDA-MB-231 breast cancer cells with enhanced green fluorescent protein (EGFP) expressing stable clone of non-metastatic MCF-7 breast cancer cells (MCF-EGFP), was used. A bystander killing effect was observed in MCF-EGFP cells cocultured with MDA-MB-231 cells pretreated with 5-FU. The striking decrease in MCF-EGFP cells, as detected by assaying for total GFP intensity, is mediated by activation of Fas/FasL system. The implication of Fas in MCF-EGFP cell death was confirmed by using antagonistic anti-FasL antibody that reverses bystander cell death by blocking FasL on MDA-MB-231 cells. In addition, inhibition of CD95/Fas receptor on the cell surface of MCF-EGFP cells by treatment with Pifithrin-alpha, a p53 specific transactivation inhibitor, partially abrogated the sensitivity of bystander MCF-EGFP cells. Our data, therefore, demonstrates that the Fas/FasL system could be considered as a new determinant for chemotherapy-induced bystander cell death in breast cancers. PMID- 17340622 TI - Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells. AB - Many space missions have shown that prolonged space flights may increase the risk of cardiovascular problems. Using a three-dimensional clinostat, we investigated human endothelial EA.hy926 cells up to 10 days under conditions of simulated microgravity (microg) to distinguish transient from long-term effects of microg and 1g. Maximum expression of all selected genes occurred after 10 min of clinorotation. Gene expression (osteopontin, Fas, TGF-beta(1)) declined to slightly upregulated levels or rose again (caspase-3) after the fourth day of clinorotation. Caspase-3, Bax, and Bcl-2 protein content was enhanced for 10 days of microgravity. In addition, long-term accumulation of collagen type I and III and alterations of the cytoskeletal alpha- and beta-tubulins and F-actin were detectable. A significantly reduced release of soluble factors in simulated microgravity was measured for brain-derived neurotrophic factor, tissue factor, vascular endothelial growth factor (VEGF), and interestingly for endothelin-1, which is important in keeping cardiovascular balances. The gene expression of endothelin-1 was suppressed under microg conditions at days 7 and 10. Alterations of the vascular endothelium together with a decreased release of endothelin-1 may entail post-flight health hazards for astronauts. PMID- 17340623 TI - In vitro differentiation of mouse bone marrow stromal stem cells into hepatocytes induced by conditioned culture medium of hepatocytes. AB - The differentiation potential of adult stem cells has long been believed to be limited to the tissue or germ layer of their origin. However, recent studies have demonstrated that adult stem cells may encompass a greater potential than once thought. In the present study, we examined whether murine bone marrow derived stromal stem cells (BMSSCs) are able to differentiate into functional hepatocytes in vitro. BMSSCs were isolated from murine femora and tibiae, and the mesodermal multilineage differentiation potentials of these cells were functionally characterized. To effectively induce hepatic differentiation, we designed a novel protocol by using hepatocyte-conditioned medium. Hepatic differentiation from mouse BMSSCs was examined by a variety of assays at morphological and molecular levels. Morphologically, mouse BMSSCs became round and epithelioid, binucleated after induction. Differentiated cells were harvested on Days 0, 10, and 20 and subjected to examination of hepatocyte characteristics by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. We detected AFP, HNF 3beta, CK19, CK18, ALB, TAT, and G-6-Pase at the mRNA and/or protein levels, hepatocyte-like cells by culture in conditioned medium further demonstrated in vitro functions characteristic of liver cells, including glycogen storage, and urea secretion. Moreover, transplantation of the differentiated cells into liver injured mice partially restored serum albumin level and significantly suppressed transaminase activity. Our findings indicated the transdifferentiation potential of mouse BMSSCs developing into the functional hepatocyte-like cells by conditioned culture medium and, hence, may serve as a model system for the study of mechanisms involved in the transdifferentiation, and a cell source for cell therapy of hepatic diseases. PMID- 17340624 TI - Inducible cAMP early repressor splice variants ICER I and IIgamma both repress transcription of c-fos and chromogranin A. AB - Inducible cAMP early repressor (ICER) splice variants are generated upon activation of an alternative, intronic promoter within the CREM gene. ICER is proposed to downregulate both its own expression, and the expression of other genes, containing cAMP-responsive promoter elements. To examine the biological function of the two ICER splice variants, I and IIgamma, in comparable cellular systems, we generated HEK 293 cell variants with controllable overexpression of either ICER I or IIgamma. These two splice variants contain two different variants of DNA binding domains. Overexpression of either ICER I or IIgamma strongly represses CRE-driven reportergene transcription but not AP1- or NFkappaB driven transcription. Thus, high specificity is maintained even at ICER overexpression. We here show that both ICER I and IIgamma repress Pituitary adenylate cyclase-activating polypeptide (PACAP)-mediated c-fos mRNA induction with similar efficiency, indicating that both splice variants play an important role in modulating PACAP-mediated transcriptional activation of the c-fos gene. ICER I and IIgamma also repress cAMP-mediated activation of chromogranin A (CgA), indicating that these splice variants may function as negative feedback regulators in CgA synthesis. The proliferation rate was not altered in cells overexpressing ICER I or IIgamma. Thus, in the epithelial cells HEK 293, ICER I and IIgamma splice variants seem to exert similar biological function. PMID- 17340625 TI - The catalytically inactive precursor of cathepsin D induces apoptosis in human fibroblasts and HeLa cells. AB - In several reports cathepsin D has been implicated in apoptosis. In some systems the effects of agents considered to be mediated by cathepsin D were inhibited in the presence of pepstatin A, an inhibitor of the enzyme. In other studies the effect of a mutant cathepsin D deprived of activity was indistinguishable from that of the normal enzyme. Here we show that in human fibroblasts and in HeLa cells apoptosis can be induced by microinjecting into cytosol either mature cathepsin D or its inactive precursor procathepsin D. The microinjected precursor remains in the uncleaved form. These results confirm that the proapoptotic effect of cathepsin D in the cytosol is independent of its catalytic activity and suggest that the interaction of cathepsin D with the downstream effector does not involve the active site of the enzyme, since in the proenzyme the active site is masked by the prosequence. PMID- 17340626 TI - Nuclear cysteine-protease involved in male chromatin remodeling after fertilization is ubiquitously distributed during sea urchin development. AB - Previously we have identified a cysteine-protease involved in male chromatin remodeling which segregates into the nuclei of the two blastomeres at the first cleavage division. Here we have investigated the fate of this protease during early embryogenesis by immunodetecting this protein with antibodies elicited against its N-terminal sequence. As shown in this report, the major 60 kDa active form of this protease was found to be present in the extracts of chromosomal proteins obtained from all developmental stages analyzed. In morula and gastrula the 70 kDa inactive precursor, which corresponds to the major form of the zymogen found in unfertilized eggs, was detected. In plutei larvas, the major 60 kDa form of this enzyme was found together with a higher molecular weight precursor (90 kDa) which is consistent with the less abundant zymogen primarily detected in unfertilized eggs. As reported here, either the active protease or its zymogens were visualized in most of the embryonic territories indicating that this enzyme lacks a specific pattern of spatial-temporal developmental segregation. Taken together our results indicate that this protease persists in the embryo and is ubiquitously distributed up to larval stages of development, either as an active enzyme and/or as an inactive precursor. These results suggest that this enzyme may display yet unknown functions during embryonic development that complement its role in male chromatin remodeling after fertilization. PMID- 17340628 TI - Anti-proliferative effects of evodiamine on human prostate cancer cell lines DU145 and PC3. AB - Prostate carcinoma is one of the most common malignant tumors and has become a more common cancer in men. Previous studies demonstrated that evodiamine (EVO) exhibited anti-tumor activities on several cancers, but its effects on androgen independent prostate cancer are unclear. In the present study, the action mechanisms of EVO on the growth of androgen-independent prostate cancer cells (DU145 and PC3 cells) were explored. EVO dramatically inhibited the growth and elevated cytotoxicity of DU145 and PC3 cells. The flow cytometric analysis of EVO treated cells indicated a block of G2/M phase and an elevated level of DNA fragmentation. The G2/M arrest was accompanied by elevated Cdc2 kinase activity, an increase in expression of cyclin B1 and phosphorylated Cdc2 (Thr 161), and a decrease in expression of phosphorylated Cdc2 (Tyr 15), Myt-1, and interphase Cdc25C. TUNEL examination showed that EVO-induced apoptosis was observed at 72 h. EVO elevated the activities of caspase 3, 8, and 9 in DU145 cells, while in PC3 cells only the activities of caspase 3 and 9 were elevated. EVO also triggered the processing of caspase 3 and 9 in both DU145 and PC3 cells. We demonstrate that roscovitine treatment result in the reversion of G2/M arrest in response to EVO in both DU145 and PC3. However, inhibitory effect of roscovitine on EVO induced apoptosis could only be observed in DU145 rather than PC3. In DU145, G2/M arrest might be a signal for initiation of EVO-triggered apoptosis. Whereas EVO triggered PC3 apoptosis might be independent of G2/M arrest. These results suggested that EVO inhibited the growth of prostate cancer cell lines, DU145 and PC3, through an accumulation at G2/M phase and an induction of apoptosis. PMID- 17340627 TI - Mitochondrial-targeted active Akt protects SH-SY5Y neuroblastoma cells from staurosporine-induced apoptotic cell death. AB - Akt is a serine/threonine protein kinase that plays a vital role in promoting cellular survival. Predominantly cytosolic, upon stimulation with growth-factors or stress, active Akt translocates into mitochondria, but the functions of Akt in mitochondria are not yet fully understood. Mitochondria play a central role in apoptotic pathways and given Akt's functions in the cytoplasm, Akt in mitochondria may help preserve mitochondrial integrity during cellular stress. To test if the translocation of Akt into mitochondria is neuroprotective, adenoviral vectors expressing a constitutively active Akt, Ad-HA-Akt (DD), and a constitutively active Akt with a mitochondrial targeting signal, Ad-Mito-HA-Akt (DD), were generated. Human SH-SY5Y neuroblastoma cells expressing the adenoviral constructs were treated with staurosporine to initiate intrinsic apoptotic cell death and several aspects of the mitochondrial apoptotic pathway were evaluated. Expression of active Akt targeted to mitochondria was found to be sufficient to significantly reduce staurosporine-induced activation of caspase-3 and caspase-9, the release of cytochrome c from mitochondria, and Bax oligomerization at mitochondria. These findings demonstrate that intramitochondrial active Akt results in efficient protection against apoptotic signaling. PMID- 17340629 TI - Palmitic acid substitution on cationic polymers for effective delivery of plasmid DNA to bone marrow stromal cells. AB - Nonviral gene carriers are actively explored in gene therapy due to safety concerns of the viral carriers. To design effective gene carriers for modification of bone marrow stromal cells (BMSC), an important cell phenotype for clinical application of gene therapy, cationic polymers polyethyleneimine (PEI), and poly-L-Lysine (PLL) were substituted with palmitic acid (PA) via amide linkages. Depending on the reaction conditions, PEI and PLL was substituted with 2.2-5.2 and 13.4-16.2 PA per polymer chain. The PA substituted polymers displayed slightly lower binding efficiency towards a plasmid containing Enhanced Green Fluorescent Protein (pEGFP) in an agarose gel binding assay. The cell binding of PLL-PA, but not PEI-PA, was particularly enhanced, resulting in higher percentage of the cells displaying a significant polymer uptake. pEGFP delivery into the BMSC was also significantly increased with the PLL-PA (vs. PLL), but not PEI-PA (vs. PEI). The transfection efficiency of PLL-PA was significantly higher ( approximately fivefold) than the unmodified polymer. We conclude that PA substitution on PLL provides an effective carrier for transfection of primary cells derived from the bone marrow. PMID- 17340630 TI - Sudden Infant Death Syndrome: review of implicated genetic factors. AB - Genetic studies in Sudden Infant Death Syndrome (SIDS) have been motivated by clinical, epidemiological, and/or neuropathological observations in SIDS victims, with subsequent pursuit of candidate genes in five categories: (1) genes for ion channel proteins based on electrocardiographic evidence of prolonged QT intervals in SIDS victims, (2) gene for serotonin transporter based on decreased serotonergic receptor binding in brainstems of SIDS victims, (3) genes pertinent to the early embryology of the autonomic nervous system (ANS) (and with a link to the 5-HT system) based on reports of ANS dysregulation in SIDS victims, (4) genes for nicotine metabolizing enzymes based on evidence of cigarette smoking as a modifiable risk factor for SIDS, and (5) genes regulating inflammation, energy production, hypoglycemia, and thermal regulation based on reports of postnatal infection, low birth weight, and/or overheating in SIDS victims. Evidence for each of these classes of candidate genes is reviewed in detail. As this review indicates, a number of genetically controlled pathways appear to be involved in at least some cases of SIDS. Given the diversity of results to date, genetic studies support the clinical impression that SIDS is heterogeneous with more than one entity and with more than one possible genetic etiology. Future studies should consider expanded phenotypic features that might help clarify the heterogeneity and improve the predictive value of the identified genetic factors. Such features should be evaluated to the extent possible in both SIDS victims and their family members. With 2,162 infants dying from SIDS in 2003 in the U.S. alone, and improved but still imperfect parent and caretaker compliance with known modifiable risk factors for SIDS, it behooves clinicians, researchers, and parents to combine efforts to reach a common goal. The message of the "Back to Sleep" campaign needs to be re-introduced/re-engineered to reach families and caretakers of all ethnic groups. Clinicians and researchers need to gently inform new SIDS parents about the opportunity to contribute tissue to the NICHD-funded University of Maryland Brain and Tissue Bank. By expanding the network of clinicians, scientists, and families working together, and by combined efforts in a collaborative multi-center study of candidate genes and/or genomics, the discovery of the genetic profile of the infant at risk for SIDS can ultimately be determined. PMID- 17340631 TI - Biological relationship between Central and South American Chibchan speaking populations: evidence from mtDNA. AB - We examined mitochondrial DNA (mtDNA) haplogroup and haplotype diversity in 188 individuals from three Chibchan (Kogi, Arsario, and Ijka) populations and one Arawak (Wayuu) group from northeast Colombia to determine the biological relationship between lower Central American and northern South American Chibchan speakers. mtDNA haplogroups were obtained for all individuals and mtDNA HVS-I sequence data were obtained for 110 samples. Resulting sequence data were compared to 16 other Caribbean, South, and Central American populations using diversity measures, neutrality test statistics, sudden and spatial mismatch models, intermatch distributions, phylogenetic networks, and a multidimensional scaling plot. Our results demonstrate the existence of a shared maternal genetic structure between Central American Chibchan, Mayan populations and northern South American Chibchan-speakers. Additionally, these results suggest an expansion of Chibchan-speakers into South America associated with a shift in subsistence strategies because of changing ecological conditions that occurred in the region between 10,000-14,000 years before present. PMID- 17340632 TI - The DNA topoisomerase IIbeta binding protein 1 (TopBP1) interacts with poly (ADP ribose) polymerase (PARP-1). AB - We investigated the physical association of the DNA topoisomerase IIbeta binding protein 1 (TopBP1), involved in DNA replication and repair but also in regulation of apoptosis, with poly(ADP-ribose) polymerase-1 (PARP-1). This enzyme plays a crucial role in DNA repair and interacts with many DNA replication/repair factors. It was shown that the sixth BRCA1 C-terminal (BRCT) domain of TopBP1 interacts with a protein fragment of PARP-1 in vitro containing the DNA-binding and the automodification domains. More significantly, the in vivo interaction of endogenous TopBP1 and PARP-1 proteins could be shown in HeLa-S3 cells by co immunoprecipitation. TopBP1 and PARP-1 are localized within overlapping regions in the nucleus of HeLa-S3 cells as shown by immunofluorescence. Exposure to UVB light slightly enhanced the interaction between both proteins. Furthermore, TopBP1 was detected in nuclear regions where poly(ADP-ribose) (PAR) synthesis takes place and is ADP-ribosylated by PARP-1. Finally, cellular (ADP ribosyl)ating activity impairs binding of TopBP1 to Myc-interacting zinc finger protein-1 (Miz-1). The results indicate an influence of post-translational modifications of TopBP1 on its function during DNA repair. PMID- 17340633 TI - Predicting DNA-binding amino acid residues from electrostatic stabilization upon mutation to Asp/Glu and evolutionary conservation. AB - Binding of polyanionic DNA depends on the cluster of electropositive atoms in the binding site of a DNA-binding protein. Such a cluster of electropositive protein atoms would be electrostatically unfavorable without stabilizing interactions from the respective electronegative DNA atoms and would likely be evolutionary conserved due to its critical biological role. Consequently, our strategy for predicting DNA-binding residues is based on detecting a cluster of evolutionary conserved surface residues that are electrostatically stabilized upon mutation to negatively charged Asp/Glu residues. The method requires as input the protein structure and sufficient sequence homologs to define each residue's relative conservation, and it yields as output experimentally testable residues that are predicted to bind DNA. By incorporating characteristic DNA-binding site features (i.e., electrostatic strain and amino acid conservation), the new method yields a prediction accuracy of 83%, which is much higher than methods based on only electrostatic strain (57%) or conservation alone (50%). It is also less sensitive to protein conformational changes upon DNA binding than methods that mainly depend on the 3D protein structure. PMID- 17340634 TI - Crystallographic, thermodynamic, and molecular modeling studies of the mode of binding of oligosaccharides to the potent antiviral protein griffithsin. AB - The mode of binding of oligosaccharides to griffithsin, an antiviral lectin from the red alga Griffithsia sp., was investigated by a combination of X-ray crystallography, isothermal titration calorimetry, and molecular modeling. The structures of complexes of griffithsin with 1-->6alpha-mannobiose and with maltose were solved and refined at the resolution of 2.0 and 1.5 A, respectively. The thermodynamic parameters of binding of 1-->6alpha-mannobiose, maltose, and mannose to griffithsin were determined. Binding profiles of 1-->6alpha-mannobiose and mannose were similar with Kd values of 83.3 microM and 102 microM, respectively. The binding of maltose to griffithsin was significantly weaker, with a fourfold lower affinity (Kd = 394 microM). In all cases the binding at 30 degrees C was entropically rather than enthalpically driven. On the basis of the experimental crystal structures, as well as on previously determined structures of complexes with monosaccharides, it was possible to create a model of a tridentate complex of griffithsin with Man9GlcNAc2, a high mannose oligosaccharide commonly found on the surface of viral glycoproteins. All shorter oligomannoses could be modeled only as bidentate or monodentate complexes with griffithsin. The ability to mediate tight multivalent and multisite interactions with high-mannose oligosaccharides helps to explain the potent antiviral activity of griffithsin. PMID- 17340635 TI - Crystal structure of human myo-inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures. AB - The human IMPA2 gene, which encodes myo-inositol monophosphatase 2 (IMPA2), is mapped onto 18p11.2, a susceptibility region for bipolar disorder. This chromosomal region has also been proposed to include a susceptibility locus for schizophrenia and febrile seizures. Here we report the crystal structures of human IMPA2 and its complex with calcium and phosphate ions. Human IMPA2 comprises an alpha-beta protein with a five-layered sandwich of alpha-helices and beta-sheets (alpha-beta-alpha-beta-alpha). The crystal structure and analytical ultracentrifugation results indicated that IMPA2 exists as a dimer in solution. The overall structure of IMPA2 is similar to that of IMPA1, except for the loop regions. In IMPA1, the loop region (31-43) is located at the entrance of the active site cavity. In the corresponding region (42-54) of IMPA2, the residues are disordered and partially form an alpha-helix. The structural difference in the opening of the active site cavity suggests that the substrate specificity differs between IMPA1 and IMPA2. The widely opened cavity of IMPA2 implies that the physiological substrate may be a larger compound than inositol monophosphate. The structure of IMPA2 complexed with Ca2+ revealed two metals and one phosphate binding sites, which were the same sites as in IMPA1 complexed with Mn2+ and phosphate, suggesting that the mechanism of the enzymatic reaction is similar to that of IMPA1. The crystal structures of human IMPA2 are useful for understanding the effect of nonsynonymous polymorphism reported in IMPA2, and will contribute to further functional analyses of IMPA2 that potentially predisposes to the vulnerabilities of bipolar disorder, schizophrenia, and febrile seizures. PMID- 17340636 TI - Magnetic resonance colonography with limited bowel preparation: a comparison of three strategies. AB - PURPOSE: To prospectively compare three strategies of magnetic resonance colonography (MRC) with fecal tagging. MATERIALS AND METHODS: Three strategies were compared: (S1) gadolinium as oral tagging agent and a gadolinium-water mixture for rectal filling (bright lumen), (S2) oral barium and water rectally, and (S3) oral barium and air rectally. In S2 and S3 (both dark lumen) gadolinium was injected intravenously. Three-dimensional (3D) T1-weighted and two dimensional (2D) T2-weighted sequences were used. Two observers scored diagnostic confidence and image quality (contrast, homogeneity, artifacts), analyzed by chi squared and Fisher's exact test. Patient experience and preference were determined by questionnaire (Mann-Whitney test). RESULTS: A total of 45 patients were included, 15 were randomly assigned per strategy. Diagnostic confidence of S1 and S3 is significantly better than for S2. S1 has the additional advantage of showing significantly better contrast between bowel wall and lumen, and showing significantly better homogeneity on both T1- and T2-weighted sequences, but with significantly more artifacts on the T1-weighted sequences. S3 showed significantly better contrast and homogeneity than S2 on the T2-weighted sequences. Bowel preparation of S1 was rated significantly better. Patient preference was comparable. CONCLUSION: Image quality was best using the bright lumen strategy or the dark lumen strategy using air for rectal filling. Although bowel preparation was rated best using the bright lumen strategy, patient preference was comparable. PMID- 17340637 TI - John Hunter and the origins of modern orthopaedic research. AB - Orthopaedic research is a multi-disciplinary, eclectic pursuit conducted in a scientific manner. John Hunter (1728-1793), the Founder of Scientific Surgery, was the first to engage systematically in this enterprise. Born in Scotland, Hunter moved to London to help his brother, William, run an anatomy school. This involved both the procurement and dissection of cadavers, for which activities John showed great aptitude. Further training and a spell as an army surgeon equipped him for his life's work as a practitioner, researcher and teacher. Hunter amassed an enormous collection of specimens displayed in a specially designed house he constructed in Leicester Square, and maintained an extensive menagerie and additional laboratories in Earl's Court. Many of his specimens are now housed in the Hunterian Museum of the Royal College of Surgeons in London. Among Hunter's contributions to orthopaedics are his discovery of bone remodeling, and his studies on the repair and regeneration of bone, cartilage and tendon. He developed numerous new surgical procedures, and provided detailed anatomical descriptions that often corrected received wisdom. Many of his pupils became famous in their own right and two of them founded the USA's first medical school. John Hunter died of a heart attack brought on by hospital administrators. PMID- 17340638 TI - Structural determinants responsible for the thermostability of Sso7d and its single point mutants. PMID- 17340639 TI - Body size and scaling of the hands and feet of prosimian primates. AB - The hands and feet of primates fulfill a variety of biological roles linked with food acquisition and positional behavior. Current explanations of shape differences in cheiridial morphology among prosimians are closely tied to body size differences. Although numerous studies have examined the relationships between body mass and limb morphology in prosimians, no scaling analysis has specifically considered hand and foot dimensions and intrinsic proportions. In this study, we present such an analysis for a sample of 270 skeletal specimens distributed over eight prosimian families. The degree of association between size and shape was assessed using nonparametric correlational techniques, while the relationship between each ray element length and body mass (from published data and a body mass surrogate) was tested for allometric scaling. Since tarsiers and strepsirrhines encompass many taxa of varying degrees of phylogenetic relatedness, effective degrees of freedom were calculated, and comparisons between families were performed to partially address the problem of statistical nonindependence and "phylogenetic inertia." Correlational analyses indicate negative allometry between relative phalangeal length (as reflected by phalangeal indices) and body mass, except for the pollex and hallux. Thus, as size increases, there is a significant decrease in the relative length of the digits when considering all prosimian taxa sampled. Regression analyses show that while the digital portion of the rays scales isometrically with body mass, the palmar/plantar portion of the rays often scales with positive allometry. Some but not all of these broadly interspecific allometric patterns remain statistically significant when effective degrees of freedom are taken into account. As is often the case in interspecific scaling, comparisons within families show different scaling trends in the cheiridia than those seen across families (i.e., lorisids, indriids, and lemurids exhibit rather different allometries). The interspecific pattern of positive allometry that appears to best characterize the metapodials of prosimians, especially those of the foot, parallels differences found in the morphology of the volar skin. Indeed, relatively longer metapodials appear to covary with flatter and more coalesced volar pads, which in turn slightly improve frictional force for animals that are at a comparative disadvantage while climbing because of their larger mass. Despite the essentially isometric relationship found between digit length and body mass across prosimians, examination of the residual variation reveals that tarsiers and Daubentonia possess, relative to their body sizes, remarkably long fingers. Such marked departures between body size and finger length observed in these particular primates are closely linked with specialized modes of prey acquisition and manipulation involving the hands. PMID- 17340640 TI - Cross-sectional study of electrocardiographic pattern in healthy children resident at high altitude. AB - Electrocardiographic studies have reported persistent right ventricle predominance in high altitude children as an adaptive response. No information was provided on ethnicity and environmental factors in those studies. We assessed the electrocardiographic characteristics in healthy high altitude children with mixed ancestry and relatively high mobility to lower altitudes. A cross-sectional study of 321 children aged 2 months through 19 years old and living at high altitude (Tintaya, Peru, 4,100 m) was conducted. Standard 12-lead electrocardiography was performed. Information was obtained on ethnicity, medical history, place and altitude of pregnancy and birth, mobility of children and their parents and grandparents to lower altitudes, and housing conditions. A medical examination, echocardiography, hemoglobin, oxygen saturation, and anthropometric measurements were performed. Means between sexes were compared through Mann-Whitney test for independent samples not normally distributed. Potentially influential variables on electrocardiographic values were controlled through a general linear model. Electrocardiographic parameters including QRS axis, RV1, RSV1, RV1SV5, RSV5, RSV6, and SV1RV5 did not show a right predominance pattern at any age. Values were within sea level norms. None of the genetic or environmental factors controlled showed a consistent influence on the electrocardiographic variables. Our study showed an electrocardiographic pattern similar to that of sea level in high altitude children with some degree of high altitude ancestry, comparatively well-nourished and with relatively high mobility to low altitudes. PMID- 17340641 TI - Dynamic MR imaging of the gastroesophageal junction in healthy volunteers during bolus passage. AB - PURPOSE: To evaluate the feasibility of noninvasive dynamic fast magnetic resonance imaging (MRI) during swallowing in healthy volunteers, and to determine esophageal function at the gastroesophageal junction during swallowing. MATERIALS AND METHODS: A total of 20 healthy volunteers underwent MRI while swallowing in the supine position. Dynamic gradient-echo (GRE) sequences (balanced fast field echo [B-FFE]) were employed in three planes on a 1.5T unit using a phased-array body coil. Buttermilk spiked with gadolinium (Gd) chelate (40:1) for bolus passage was used as an oral contrast agent. We evaluated visualization of esophageal bolus transit, bolus transit time (BTT), peristalsis, identification of the gastroesophageal junction, and reflux during the Valsalva maneuver. RESULTS: The mean visible length of the esophagus was 16.2+/-5.3 cm in the sagittal view, and 13.8+/-4.9 cm in the coronal view. In the sagittal view the BTT was defined in 15 of 20 volunteers and was 7.6+/-1.4 seconds. The BTT in the coronal view was measured in seven of 20 volunteers and was 8+/-1.3 seconds on average. The axial view yielded higher scores (2.25) than the coronal (1.98) and sagittal (1.78) views for identification of the cardia and during the Valsalva maneuver. Bolus contrast was better displayed in the sagittal (2.2) view than in the coronal (2.08) or axial (1.73) planes. In six volunteers, gastroesophageal abnormalities, such as axial hernia, reflux, and nonperistaltic contractions, were identified. For statistical analysis we used the Friedman test and a one-way analysis of variance (ANOVA). CONCLUSION: The results indicate that dynamic MR swallowing is a feasible and reproducible technique that warrants further studies in patients. PMID- 17340642 TI - Proteomics for everyday use: activities of the HUPO Brain Proteome Project during the 5th HUPO World Congress. AB - Long Beach hosted this year's annual congress of the Human Proteome Organisation (HUPO). In addition to the numerous sessions, talks and poster presentations organized by HUPO itself, several events were arranged by the HUPO initiatives. The Brain Proteome Project (HUPO BPP) was very active, initiating three pre congress workshops: (i) the kick-off meeting of the EU-funded ProDaC consortium (Proteomics Data Collection) that is aiming at the bioinformatics Standardization in the proteomics field; (ii) the workshop "Standardization Issues in Proteomics: Perspectives from Vendors" giving an overview about the lessons learned by proteomics industrial partners; (iii) the 6th HUPO BPP Workshop "New Proteomics Approaches for further HUPO BPP Studies" offering new concepts for brain-related proteomics studies. PMID- 17340643 TI - The HUPO pre-congress Proteomics Standards Initiative workshop. HUPO 5th annual World Congress. Long Beach, CA, USA 28 October-1 November 2006. AB - The plenary session of the Proteomics Standards Initiative of the Human Proteome Organisation provided an opportunity to update delegates on the progress of the work of the Human Proteome Organisation's Proteomics Standards Initiative (HUPO PSI) to develop and implement standards in the field of proteomics. Significant advances have been made since the previous congress, with several of the interchange standards and minimal requirements documents being submitted for publication in the literature and being more widely adopted by both manufacturers and data repositories. An exciting development over the interim twelve months is the ongoing merger of the two existing mass spectrometry standards, the PSI mzData and Institute for Systems Biology mzXML, into a single product. This should be achieved by early in 2007. PMID- 17340644 TI - Publication Committee meeting. HUPO 5th annual World Congress. Long Beach, CA, USA 30 October 2006. AB - This meeting brought together delegates from industry, academia and the publishing houses to facilitate discussions on the level of support from the journals for the use of standardised data formats and their interest in the creation of a network of proteomics repositories collaborating on a coordinated data curation effort. Discussions centred on how best to structure interactions between journals, databases and researchers to improve accessibility to data, and facilitate comparisons between datasets. PMID- 17340645 TI - Quantitative analysis of thiols in consumer products on a microfluidic CE chip with fluorescence detection. AB - A microchip CE-based method for the quantification of the thiols mercaptoethanoic acid (MAA) and 2-mercaptopropionic acid (2-MPA) in depilatory cream and cold wave lotions was developed. The thiols were first derivatized with the fluorogenic reagent ammonium-7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate (SBD-F). The derivatives were separated within only 20 s by microchip CE and detected by their fluorescence. Conventional CE with diode array detection and LC with fluorescence detection were used for validation. The internal standard 3-mercaptopropionic acid (3-MPA) provided RSDs of multiple injections of only 4% or less for the MCE approach. LOD is 2 microM, LOQ 6 microM, and the linear range comprises nearly three decades of concentration starting at the LOQ. PMID- 17340646 TI - Thermoset polyester as an alternative material for microchip electrophoresis/electrochemistry. AB - Microchip CE coupled with electrochemical detection (MCE-EC) is a good method for the direct detection of many small molecule analytes because the technique is sensitive and readily miniaturized. Polymer materials are being increasingly used with MCE due to their affordability and ease of fabrication. While PDMS has become arguably the most widely used material in MCE-EC due to the simplicity of microelectrode incorporation, it suffers from a lack of separation efficiency, lower surface stability, and a tendency for analyte sorption. Other polymers, such as poly(methylmethacrylate) (PMMA) and poly(carbonate) (PC), have higher separation efficiencies but require more difficult fabrication techniques for electrode incorporation. In this report, thermoset polyester (TPE) was characterized as an alternative material for MCE-EC. TPE microchips were characterized in their native and plasma oxidized forms and after coating with polyelectrolyte multilayers (PEMs). TPE provides higher separation efficiencies when compared to PDMS microchips, while still using simple fabrication protocols. In this work, separation efficiencies as high as 295,000 N/m were seen when using TPE MCE-EC devices. Furthermore, the EOF was higher and more consistent as a function of pH for both native and plasma-treated TPE than PDMS. Finally, TPE is amenable to modification using simple PEM coatings as another way to control surface chemistry and surface charge. PMID- 17340647 TI - Effect of CyDye minimum labeling in differential gel electrophoresis on the reliability of protein identification. AB - Differential 2-DE (DIGE) is a widely applied tool for the quantitative analysis of differentially represented proteins. The method involves covalent minimal labeling of proteins prior to their electrophoretic separation using CyDye DIGE Fluor minimal dyes. This methodology creates two different species per protein, the labeled (approx. 1-2%) and unlabeled (approx. 98-99%) ones, which differ in their molecular masses by 434-464 Da, depending on the attached dye. DIGE followed by automated spot picking according to the CyDye coordinates misses in many instances the exact positions where the maximum amounts of the considered proteins are located. This fact leads to a loss in sensitivity of the subsequent MALDI-MS analyses and results in a reduced reliability of protein identification and sequence coverage. In this paper, the migration differences of labeled and unlabeled species are quantified together with the impact of this effect on the certainty of protein identification and sequence coverage investigating proteins up to 90 kDa. PMID- 17340648 TI - Crystalline small-molecule electrolytes. PMID- 17340649 TI - Efficient synthesis and resolution of pyrrolizidines. PMID- 17340650 TI - Structural transformation of a two-dimensional molecular network in response to selective guest inclusion. PMID- 17340651 TI - Rh-catalyzed highly enantioselective synthesis of 3-arylbutanoic acids. PMID- 17340652 TI - Regioselective eightfold and tenfold additions of a pyridine-modified organocopper reagent to [60]fullerene. PMID- 17340653 TI - The click reaction in the luminescent probing of metal ions, and its implications on biolabeling techniques. PMID- 17340654 TI - An open trial of aripiprazole augmentation for SSRI non-remitters with late-life depression. AB - OBJECTIVE: To evaluate the efficacy and tolerability of aripiprazole augmentation in elderly depressed patients who did not reach remission after treatment with an SSRI. METHOD: Outpatients 50 years and older with major depressive disorder not remitting after adequate treatment with an SSRI were eligible for the study. In the 6-week long augmentation phase, antidepressants were continued without change and aripiprazole was titrated if needed to a maximum dose of 15 mg per day. Patients were evaluated at the study endpoint on an intent to treat basis, and the primary outcome measure was remission of depression as measured by Hamilton Rating Scale for Depression (HRSD) 23 microM). Chiral discrimination for [Pt(S,S-dach)(phen)](ClO(4))(2) over its R,R enantiomer was observed in all 13 cancer cell lines investigated. Moreover, [Pt(S,S-dach)(phen)](ClO(4))(2) was more active than cisplatin in all cell lines tested and shows only partial cross-resistance to cisplatin in two cisplatin resistant cell lines. PMID- 17340670 TI - A glucose derivative as natural alternative to the cyclohexane-1,2-diamine ligand in the anticancer drug oxaliplatin? AB - Having oxaliplatin as archetype, several platinum complexes with a carbohydrate moiety resembling the cyclohexane-1,2-diamine ligand of oxaliplatin have been prepared. As leaving groups, the anionic ligands iodide, oxalate, and malonate were utilized, and for comparison purposes the chloro complex was employed. All compounds were characterized by elemental analysis, nuclear magnetic resonance spectroscopy, and electrospray mass spectrometry. The crystal structure of (SP-4 3)-diiodo(2,3-diamino-2,3-dideoxy-D-glucose-kappa(2)N,N')platinum(II) was determined by X-ray diffraction. The affinity toward dGMP was assayed by capillary electrophoresis, revealing that the chloro complex shows the highest reactivity, followed by the iodo complex. In contrast, the binding kinetics of the dicarboxylato complexes are slower, with the malonato complex being the least reactive. Reactivity to dGMP in the cell-free system correlates with cytotoxicity in two of four human cancer cell lines as determined by means of the MTT assay. In three of the four cell lines, the chloro and the malonato complex are the most and the least active of the carbohydrate-Pt complexes, respectively, with IC(50) values differing only by factors of up to 3.2. Cytotoxicity of the chloro complex is one to two orders of magnitude lower than that of oxaliplatin, but still comparable to that of carboplatin in two of the four cell lines. PMID- 17340671 TI - Pyramiding of insecticidal compounds for control of the cowpea bruchid (Callosobruchus maculatus F.). AB - The cowpea bruchid (Callosobruchus maculatus F.) (Chrysomelidae: Bruchini) is a major pest of stored cowpea grain. With limited available technologies for controlling the bruchid, transgenic cowpeas with bruchid resistance genes engineered into them could become the next management tools. An investigation was made of two different sets of potential transgenic insecticidal compounds using an artificial seed system: (i) CIP-PH-BT-J and recombinant egg white avidin, and (ii) avidin and wheat alpha-amylase inhibitor. CIP-PH-BT-J (0.1%; 1000 mg kg(-1)) and recombinant egg white avidin (0.006%; 60 mg kg(-1)) incorporated separately into artificial seeds caused 98.2 and 99% larval mortality rates respectively. Combining CIP-PH-BT-J and avidin in the same artificial seed provided additional mortality compared with each factor incorporated singly; no insects survived in seeds with the combined toxins. Similarly, when avidin and wheat alpha-amylase inhibitor (alphaAI) (1%; 10 g kg(-1)) were incorporated separately into artificial seeds, this caused 99.8 and 98% mortality respectively. However, in combination, avidin and alphaAI did not increase mortality, but they did cause a significant increase in developmental time of the cowpea bruchids. These results emphasize that the joint action of potential insecticidal compounds cannot be predicted from results obtained separately for each compound, and they suggest potential transgenes for further consideration. PMID- 17340672 TI - Multiple imputation for correcting verification bias by Ofer Harel and Xiao-Hua Zhou, Statistics in Medicine 2006; 25:3769-3786. PMID- 17340673 TI - Electron- and energy-transfer properties of hydrophilic carotenoids. AB - The antioxidant activities-expressed as the electron-donating properties-of five hydrophilic carotenoids (carotenoid surfactants) and three related hydrophobic carotenoids were investigated by flash photolysis. The electron-transfer rates of the carotenoids to the triplet state of the sensitizer 2-nitronaphthalene and the energy transfer rates of triplet 2-nitronaphthalene to the carotenoids were determined. The results demonstrate that the electron-donating effects of the hydrophilic and hydrophobic carotenoids were comparable when evaluated in acetonitrile. In the presence of water, however, electron transfer (i.e., antioxidant efficiency) was enhanced by a factor of four for the hydrophilic carotenoids. The increased hydrophilicity of carotenoids, therefore, could expand their antioxidant properties, thus facilitating their use as aqueous-phase radical scavengers. At the same time, it was shown that supramolecular assembly ("aggregation") of the amphiphilic carotenoids prevented electron transfer, thus deactivating the antioxidant function. Modulation of the biophysical properties of carotenoids through synthetic modification is capable of increasing the biological and medical utility of this natural class of predominantly hydrophobic antioxidant compound. PMID- 17340674 TI - Stereoselective ring-opening polymerization of a racemic lactide by using achiral salen- and homosalen-aluminum complexes. AB - Highly isotactic polylactide or poly(lactic acid) is synthesized in a ring opening polymerization (ROP) of racemic lactide with achiral salen- and homosalen aluminum complexes (salenH(2)=N,N'-bis(salicylidene)ethylene-1,2-diamine; homosalenH(2)=N,N'-bis(salicylidene)trimethylene-1,3-diamine). A systematic exploration of ligands demonstrates the importance of the steric influence of the Schiff base moiety on the degree of isotacticity and the backbone for high activity. The complexes prepared in situ are pure enough to apply to the polymerizations without purification. The crystal structures of the key complexes are elucidated by X-ray diffraction, which confirms that they are chiral. However, analysis of the (1)H and (13)C NMR spectra unambiguously demonstrates that their conformations are so flexible that the chiral environment of the complexes cannot be maintained in solution at 25 degrees C and that the complexes are achiral under the polymerization conditions. The flexibility of the backbone in the propagation steps is also documented. Hence, the isotacticity of the polymer occurs due to a chain-end control mechanism. The highest reactivity in the present system is obtained with the homosalen ligand with 2,2-dimethyl substituents in the backbone (ArCH==NCH(2)CMe(2)CH(2)N==CHAr), whereas tBuMe(2)Si substituents at the 3-positions of the salicylidene moieties lead to the highest selectivity (P(meso)=0.9(8); T(m)=210 degrees C). The ratio of the rate constants in the ROPs of racemic lactide and L-lactide is found to correlate with the stereoselectivity in the present system. The complex can be utilized in bulk polymerization, which is the most attractive in industry, although with some loss of stereoselectivity at high temperature, and the afforded polymer shows a higher melting temperature (P(meso)=0.9(2), T(m) up to 189 degrees C) than that of homochiral poly(L-lactide) (T(m)=162-180 degrees C). The "livingness" of the bulk polymerization at 130 degrees C is maintained even at a high conversion (97-98 %) and for an extended polymerization time (1-2 h). PMID- 17340675 TI - On the mechanism of action and selectivity of the corn herbicide topramezone: a new inhibitor of 4-hydroxyphenylpyruvate dioxygenase. AB - Topramezone is a new, highly selective herbicide of pyrazole structure for the post-emergence control of broadleaf and grass weeds in corn. The biokinetic properties and mode of action of topramezone were investigated in plants of Setaria faberi Herrm, Sorghum bicolor (L.) Moench, Solanum nigrum L. and the crop species corn (Zea mays L.). Within 2-5 days after treatment, topramezone caused strong photobleaching effects on the shoot, followed by plant death of sensitive weeds. The selectivity of topramezone between corn and the weed species has been quantified as above 1000-fold. By virtue of the plant symptoms and the reversal of the effects in Lemna paucicostata L. by adding homogentisate, it was hypothesized that topramezone blocks the formation of homogentisate, possibly through inhibition of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD). Indeed, topramezone strongly inhibited 4-HPPD activity in vitro, with I(50) values of 15 and 23 nM for the enzyme isolated from S. faberi and recombinant enzyme of Arabidopsis thaliana L. respectively. The enzyme activity from corn was approximately 10 times less sensitive. After root and foliar application of [(14)C]topramezone, equivalent to field rates of 75 g ha(-1), the herbicide was rapidly absorbed and systemically translocated in the plant. Only marginal differences between leaf uptake and translocation of topramezone by the weeds and corn were found. Metabolism of foliar-applied [(14)C]topramezone was far more rapid in corn than in the weeds. A more rapid metabolism combined with a lower sensitivity of the 4-HPPD target enzyme contributes to the tolerance of corn to topramezone. PMID- 17340676 TI - Estimating and testing interactions in linear regression models when explanatory variables are subject to classical measurement error. AB - Estimating and testing interactions in a linear regression model when normally distributed explanatory variables are subject to classical measurement error is complex, since the interaction term is a product of two variables and involves errors of more complex structure. Our aim is to develop simple methods, based on the method of moments (MM) and regression calibration (RC) that yield consistent estimators of the regression coefficients and their standard errors when the model includes one or more interactions. In contrast to previous work using structural equations models framework, our methods allow errors that are correlated with each other and can deal with measurements of relatively low reliability. Using simulations, we show that, under the normality assumptions, the RC method yields estimators with negligible bias and is superior to MM in both bias and variance. We also show that the RC method also yields the correct type I error rate of the test of the interaction. However, when the true covariates are not normally distributed, we recommend using MM. We provide an example relating homocysteine to serum folate and B12 levels. PMID- 17340677 TI - Georgia on the mind. PMID- 17340678 TI - Bibliography. Current world literature. Small intestine. PMID- 17340679 TI - XDR tuberculosis spreads across South Africa. PMID- 17340680 TI - US campaign tackles drug company influence over doctors. PMID- 17340681 TI - European Parliament slammed over tobacco talks. PMID- 17340682 TI - Evidence based medicine: what it is and what it isn't. 1996. PMID- 17340683 TI - Hyperhomocysteinemia and cobalamin disorders. PMID- 17340684 TI - Open access: the dust hasn't settled yet. PMID- 17340685 TI - Be safe, be prepared: emergency system for advance registration of volunteer health professionals in disaster response. PMID- 17340686 TI - Domestic violence: the challenge for nursing. PMID- 17340687 TI - Integrating generational perspectives in nursing. PMID- 17340688 TI - Is the Doctor of Nursing Practice ethical? PMID- 17340689 TI - The Doctor of Nursing Practice (DNP): need for more dialogue. PMID- 17340690 TI - Disillusioned and anxious. PMID- 17340691 TI - [Long-term results in experimental lymph node-vein anastomosis]. AB - Experimental results with iliocaval lymph node-vein anastomosis are reported. Good long-term lymph-venous exchange is attributed to the fundamental details of the technique. A description and some illustrative drawings are presented. PMID- 17340692 TI - [Distribution and metabolism of testosterone in rats]. AB - Distribution and metabolism of testosterone were studied in male and female rats. While no differences between sexes were observed in the hormone distribution to liver, kidney, spleen, heart, adipose tissue, muscle, brain and adrenal, male liver was found to metabolize testosterone mainly to polar compounds; female liver mainly to A-ring reduced compounds. PMID- 17340693 TI - [Influence of estradiol on hepatic testosterone metabolism in vitro]. AB - The influence of estradiol and of two electron donors (succinate and malate) on testosterone metabolism was studied in vitro. In presence of estradiol the metabolic pattern of testosterone in male liver was changed to a female pattern. On the contrary, addition of malate or succinate to the female liver incubate gave origin to polar metabolites of testosterone which are typical of the male metabolic pattern. PMID- 17340694 TI - [Intestinal mucosa absorption and esterification of 14C oleic acid during treatment with neomycin]. AB - Neomycin administered to rats subjected to lymphatic fistula and treated with 14C labelled oleic acid did not decrease either the absorption or the esterification of this organic acid. The results appear to indicate that neomycin has no effect on the intestinal mucosa. PMID- 17340695 TI - [14C-labelled triolein absorption and esterification in rats treated with neomycin]. AB - Intragastrically administered 14C-triolein was observed in fistula-derived lymph from rats treated with neomycin and controls. Absorption was much reduced in the treated animals, indicating (contrary to the literature data) that neomycin malabsorption also occurs in this species. The slight amount absorbed followed normal routes. It is suggested that the antibiotic acts on the intestinal content and not on the mucosa. PMID- 17340696 TI - [Histological pathology of the anterior abdominal musculature in old age in relation to postoperative laparocele]. AB - The causes of postoperative laparocele in the aged were investigated. Particular attention was paid to the possibility of predisposing factors represented by senile changes in the abdominal muscles. Histological examination of 50 muscle specimens showed that dystrophy and degeneration, with possible loss of tone and firmness, were common after the age of 60 yr, with the result that laparocele might occur even in the absence of the usual causes. PMID- 17340697 TI - [Modern views on the physiopathology of the foetal thyroid]. AB - Data from the recent literature are cited in an account of the main physiological and physiopathological features of the foetal and neonatal thyroid. The picture in both the gravid and the foetus is discussed and particular attention is paid to the main instances of hypo- and hypersecretory dysfunction in the neonate in relation to the changes induced in the maternal thyroid by various factors. PMID- 17340699 TI - [A case of primary lymphosarcoma of the stomach]. AB - The presentation of a case of primary lymphosarcoma of the stomach is made the occasion for a survey of the anatomopathological, clinical and therapeutic features of this disease and of its diagnostic pitfalls. PMID- 17340698 TI - [Changes in the visual field induced by intrasellar implantation of 90Y in 104 acromegalic patients and their subsequent course]. AB - Changes in the visual field and their correction by intrasellar implantation of 90Y were assesed in 104 acromegalic patients. The results indicated that this form of examination is extremely useful in the evaluation of pituitary adenoma size. The value of intrasellar implantation of radioactive substances was demonstrated by the regression of visual field alterations in a very high percent of cases. PMID- 17340700 TI - [Notes on the aetiopathogenesis, clinical picture and treatment of rupture of the uterus during labour. Apropos of a case]. AB - The aetiopathogenesis, clinical picture and anatomopathological features of spontaneous rupture of the uterus during labour are examined and reference is made to a personal case in which the ensuing massive haemorrhage necessitated hysterectomy. A pathogenetic interpretation of this serious complication is based on the findings. PMID- 17340701 TI - [Work ability of workers from an information technology company]. AB - Cross sectional epidemiological study aimed to assess the work ability of workers at a telecommunications and information technology company. The Work Ability Index (WAI) developed by Finnish researchers was used along with a questionnaire dealing with lifestyle and sociodemographic data. The study comprised 173 subjects, 60.1% male, average age 42.2 years, 78% married, 72.8% college graduates, 13.9% held a second job, 69.4% exercised regularly, only 12.1% were smokers and 50.3% drank alcoholic beverages. Medically diagnosed diseases were reported by 66.5%. Light mental illness was the most frequent. Among the interviewees, work ability was moderate (9.2%), good (42.2%) and excellent (48.6%). The logistic regression model pointed out that workers who do not get physical exercise run 2.5 times more the risk of having a moderate/good WAI. PMID- 17340702 TI - [Visitation in the ICU: a meeting of the unknown]. AB - The aim was to describe the visitors' conceptions about assistance they receive from the nursing group as well as to identify their needs. It is a descriptive study using qualitative approach, based on an intensive care's observation in a hospital from Rio de Janeiro, with 12 visitors of patients under hospitalization. The data were collected by a semi-structured interview. The results mark despair, fear of death anguish, visitors feelings and they have to be taken into consideration. In relation to the care they pointed out the value of interaction in the reception, they wish to increase communication and total conscience of procedure inferring in the way care is delivered and also want to know everything possible about procedures. They point out the need of better information and wish the best care for the patiente and receives a good treatment. PMID- 17340703 TI - [Family health program: a space for the reconstruction of social representations of the health-disease process?]. AB - A qualitative study that investigated the social representations of health disease process of families accompanied by Family Health Program (FHP) in the rural zone in the municipal of Lafaiete Coutinho, Bahia, Brazil, aiming at analyzing the social representations of families about the health-disease process. Data were colected through a semi-structured interview with 23 members of several families. Content analysis was used do understand sense nucleous. The results showed that the FHP interferes in the reconstruction of social representations of health-disease process, through the organization of health services and of social production of health. It was concluded the FHP has contributed for the democratization of knowbdge of health-disease process, however it is necessary to dimystify cultural values reinforced by a model of attention that emphasized the recovery of diseases. PMID- 17340704 TI - [The nurse's administrative point of view in the hospitalar macro system: a reflexive study]. AB - The study aimed at investigating the nurses' administration points of view concerning managing activities in the hospital macro-system, based on the Administration Contingent Theory A group of 9 nurses responsible for the administration of nursing services at 6 reference hospitals in Fortaleza/Ceara, participated of the study. Data were assessed by means of free interview techniques, from August to December 2001. The results suggest that the administrative approach focused the development of Leadership and Control activities. The interview outcomes reveal that nursing administration in a Hospital Macro-system was not perceived as an easy task, but feasible nevertheless. The greatest difficulty seemed to be due to a poor reflexive practice about the nurse's administrative attributions. PMID- 17340705 TI - [Action of the nurse with peripherally inserted central catheter in the newborn infant]. AB - Technological advances in Neonatology have benefited the infant newborn who need a safe venous access. This study aimed at investigating the actions of the nurse regarding Peripherally Inserted Central Catheter (PICC) in the Neonatal Intensive Care Unit in Fortaleza, CE. The sample was composed by 17 nurses; the data were collected from July to August 2004 through a structured questionnaire. In the results, it was verified that 09 nurses reported the basilic vein as the most indicated for puncture; 17 reported the washing the hands before and after handling the catheter and washing it before and after the drug administration as the most important care. It was concluded that handling this device requires knowledge and hability on the part of the professionals. PMID- 17340706 TI - [Significant situations in the space and context of hemodialysis: what do users say about?]. AB - A qualitative study performed at a hemodialysis clinic in the interior of Parana. Semi-structured interviews were used to look at significant situations for chronic renal patients, experienced in the space and context of hemodialytic treatment. The results indicated difficulties associated with the communication process, causing discomfort and a feeling of helplessness, especially at the beginning of the treatment. It was shown that importance was assigned to the family, to the relationship with the other service users and with the members of the health care team, as a way of contributing to the recovery and adaptation process, amidst the adversities imposed by the disease and treatment. Aspects related to the presentation, esthetics and cleanliness of the environment also emerged as factors that interfere in client satisfaction. PMID- 17340707 TI - [Forming teachers: the educational practice in a graduate nursing program]. AB - This study aimed at understanding the educational practices operated in the Graduate Nursing Program of the Center of Sciences of the Health of the Federal University of Paraiba-UFPB and at identifying the produced contradictions, to the light of emancipatory pedagogic references and also non-emancipatory ones. This is a study of qualitative approach. The teachers and students of the Graduate Nursing Program of UFPB were the subject of the study. The semi-structured interview was used, and the analysis of the data happened through the technique of speech analysis. The evidenced empiric categories were: Contradictions in the Process of Formation of Teachers and Influence of the Educational Emancipatory ando non-Emancipatory Practices. It was verified that the teachers' Educational Practice is found in bases of non-Emancipatory, fact ratified by the speech of the students. PMID- 17340708 TI - [Nursing care to elderly patients undergoing heart catheterization: a proposal according to the Adaptation Model of Calista Roy]. AB - The study aimed at identifying the nursing diagnoses related to the psychological and social aspects of elderly patients undergoing cardiac catheterization, according to the Adaptation Theory of Calista Roy. It was developed in a cardiology unit in a hospital in Fortaleza, CE, from January to July, 2005. A semistructured interview was used, with 18 elderly patients, in pre catheterization period. The analysis identified the nursing diagnoses: alteration in the maintenance of the health, anxiety fear and alteration in the family process. The nursing actions were: to create a trust climate for the aged before the exam; to listen and to respect feelings faiths and referring values to the situation; to guide the patient with relationships to the procedure. The use of this theory, allowed in recognizing that patients, by means of incentives, can unchain answers some positive times other negative times, fitting to the nurse to act as mediator PMID- 17340709 TI - [Midwives and care in childbirth]. AB - This study aimed at knowing the care in childbirths conducted by midwives by the middle of 20th century It is a study of qualitative approach using as reference the Content Analysis. Four midwives were interviewed. Five categories emerged: Motivation to be a midwife; learning to be a midwife; positioning the midwife's work; developing care; work compensation. Midwives sought this occupation for institutional and job need. They learned the work in courses and practice. At home, conditions were poor, and in hospitals, they conducted the majority of the childbirth. They took the necessary care for mother and child. They have reported to be patient so that mothers could have normal childbirth. They conducted with selflessness because social recognition was their compensation. PMID- 17340710 TI - [Intrusion's feeling of personal and territory space of the patient]. AB - This study aims to identify the patients' feelings in relation to the intrusion of their personal and territorial space. It was used the Scale of Measurement of Feeling's Intrusion of the Personal and Territory Space with forty patients. The data pointed out that the patients feel more invaded in their territory space than in their personal space. The instrument resulted in high internal consistency for both subscales, physical space (alpha = 0.88) and personal space (alpha = 0.85). It is highlighted the role of the nurse concerning the importance of better adapting the distribution of these spaces, aiming to minimize these feelings on the patient. PMID- 17340711 TI - [Evaluation of the satisfaction level of cancer patients with the assistance recieved during ambulatory antineoplastic chemoteraphy]. AB - This descriptive study, grounded upon Donabedian's outcomes approach, had as purpose to evaluate the satisfaction level of cancer patients with the assistance received at the Adult Chemotheraoy Ambulatory of Hospital Sao Paulo. The sample was constituted of 105 patients who accepted to participate in the study The patients' evaluation was positive both with nursing care (54% very good and 46% good) and with the overall care received in that service (50% very satisfied and 46% satisfied). The level of satisfaction manifested by the clients was related mainly to the organization accessibility, the welcoming environment and the assistance process, in its professional/client interaction and the technical performance dimensions. However, they also pointed out the need for measures aimed at preventing drugs shortage and the lack of vacancies for new patients. PMID- 17340712 TI - [Stress: risk factors on hospital nurse's work]. AB - This study aimed at describing the demographic-social features and the working of the studied population and to identify the variable that presents major risks for the stress. The populations was constituted of 85.1% of nurses workers from a hospital. They answered to the stress scale. Data were analyzed using distribution frequency, relative risk and test c2 (p < 0.05). 87.5% of nurses are female, 33.4% work from 10 a 15 years and 45.8% have double vinculum of work. Facing critical situations was the variable with major risk for stress. It was verified that how bigger is the zone age of nurses bigger will be the stress for the personal management. PMID- 17340713 TI - [Nursing teaching in Lajeado, RS: a historical recovery]. AB - Historical qualitative research whose aim has been to recover nursing teaching path in the Brazilian town of Lajeado/RS, from the second half of the twentieth century. Oral history has been used as primary data, and the second ones have been documents that have been analysed according to Bardin's Content Analysis. The subjects were heads, teachers and students of nursing courses. In the past 50 years, the professionalization of nursing was intensive, serving to the current political and economic model, in the form of formal and informal courses. Workers would be ill prepared, subservient to other health professionals and would try to work for doctors and institutional directors. However, school initiative and professionals working in various areas began to change this reality in the region. PMID- 17340714 TI - [Systematization of nursing assistance: subsidies for implementation]. AB - This study reviews national literature about the Systematization of Nursing Assistance in order to detect and reflect on the phases of its implementation. An electronic search of the data bases at LILACS, MEDLINE and BDENF revealed 61 published studies on this subject in nursing journals. This present study focuses on negative experiences regarding its implementation and presents a strategy for its successful implementation. The plan was observed to have various phases, but it was observed that the institution's structure, facilities and demands had to be first studied. It was concluded that the process for its implementation would be complex and difficult, but could contribute towards improving the quality of nursing care. PMID- 17340715 TI - [Cooperation versus collaboration: concepts for nursing teaching in virtual environment]. AB - This paper presents the concepts of cooperation and collaboration in the light of Jean Piaget's theory The importance of his theory resides in the increasing use of virtual learning environments for nursing teaching; these virtual environments enable group work and the development of projects under a constructivist interactionist perspective. Social exchange relations take place between learning subjects; there is cooperation when there is construction of knowledge and collaboration when there are exchanges of thoughts, just as it happens in verbal communication. Understanding these concepts enables one to understand the dimension developed in pedagogical activities in nursing education proposed in a virtual environment. PMID- 17340716 TI - [Medicine administration: analysis of nursing scientific production]. AB - The review had as objective to analyse the nursing scientific production about the medicine administration, during the period from 1999 to 2004. For the search of the articles it was consulted articles of nursing index in Medline and LILACS databases during the period from April to June 2005. It was found 25 articles in 7 journals indexed in Qualis, national and international articles, categories A and B. We chose content analysis and system of categorization. We verified that scientific production is about several aspects, pointing the need of studies about ethics issues. We concluded that care must be expressed taking in consideration the diverse human aspects. PMID- 17340717 TI - [Music as a resource in care for hospitalized children: a possible intervention?]. AB - This bibliographic study involved the Medline and LILACS databases as well as non systematized searches and covered the period from 1994 to 2004. We aimed to analyze the bibliographic production on pediatric nursing and music, in order to identify current knowledge in this area. Our analysis revealed 3 units of meaning: the setting, interventions and repercussions. The results disclose the benefits music can offer to hospitalized children, their family members and health teams. We observed that music can be used in hospitals as a low-cost, nonpharmacological and noninvasive intervention, promoting development processes with a view to the health of children, families and workers. PMID- 17340718 TI - [Vygotsky's Social-Historic Constructivism and nursing]. AB - The aim of this paper is to reflect, in the theoretical scope, about the Vygotsky's socio-historical constructivism and the contributions from this Russian researcher to build the nursing knowledge. The Vygotskian approach has as its philosophical, epistemological and methodological purposes, the principles of the historical materialism, it emphasizes the social and cultural context in the working process, also in the use of instruments and in the dialectical interaction between human beings and environment. We understand that the ideas preconized by Vygotsky can represent an alternative method to the practical and theoretical studies, specially, as the subjective dimension of the working process near by the nursing staff. PMID- 17340719 TI - [Midwive-nurses and nurse-midwives: the interface of professionals sharing affinity, but differences]. AB - In 2005, the Midwifery course at undergraduate level was created at the University of Sao Paulo, which has intensified discussions about educational models for non-medical professionals for delivery care. This study aims at deepen the understanding of meanings related to re-starting the mentioned course at the present moment involving delivery and childbirth care. Past events that have influenced models for delivery care by non-medical personnel were considered: the enactment of a law for midwives in England, in 1902, which included this practice into the official national health system, the traditional midwife work in the U.S.A. considered as peripheral and emblematic moments dispute between nurses and midwives in Brazil. PMID- 17340720 TI - [Hospital infection and the historical evolution of infection]. AB - The author describes the historical evolution of infection and its treatment so as to trace an interface of these issues and the modern panorama of epidemiology and control of hospital infection. This study reviews data on treatments that have been used since the Middle Ages, including from myths and popular beliefs to data that has been the object of scientific microbiological and therapeutic evaluation. The study takes into consideration the fact that the rebirth of science during the Renaissance, along with appearance of the press, which made the publication of news and pictures on illness possible, contributed to the evolution of science and its technology. PMID- 17340721 TI - [Trajectory and trends of Brazilian nursing diploma courses]. AB - The text analyzes the path of the education in nursing in Brazil and analyzes the trends of the diploma courses (1991-2004) and describes a profile of the nursing graduation students that participated in the National Exam of Courses (ENADE), in 2004. To draw the referred profile 18 partner-family indicators and the respondents of the student's questionnaire academics they used. Some perspectives and challenges are pointed to the education in nursing in the country, with views to subsidize educators and students in his/her academic practice. PMID- 17340722 TI - [Nursing education: building up the integrality of care]. AB - In this study it was aimed to understand the nursing teaching towards the integrality of healthcare. A qualitative approach study with data obtained from interviews with members of the teaching staff, student nurses and nurses of services. The transcribed interviews were submitted to discourse analysis. Intentionalities shown by the research participants regarding the professional training from the perspective of the integrality of healthcare in a movement of overcoming the flexnerian paradigm towards a possibility of critical and reflective education were seen. It was concluded that the nursing training points at reflections on the changing movement on the pedagogical practices and healthcare as fundamental strategy in order to build the integrality of healthcare. PMID- 17340723 TI - [Maternal/familiar knowledge in relation to care provided to sick children]. AB - Improving family and community practices is one of the components of the strategy Integrated Management of Childhood Illness (IMCI). Considering that In Brazil, IMCI is being implemented in the context of Family Health Program (PSF), the objective of this study was to identify maternal knowledge in relation to care provided to child with respiratory disease or diarrhea in two health units with different assistance models, with PSF and without PSF The results showed that the level of maternal/familiar knowledge were similar in both assistance models. Under a scientific point of view, the mothers/families showed overshot knowledge in relation to care provided to child with diarrhea. The finding show that mother and caretaker communication need to improve, even health units with PSF. PMID- 17340724 TI - [The teaching of play/therapeutic play in nursing schools in Sao Paulo State]. AB - This study is a descriptive and quantitative research that aims to characterize the toy/therapeutic toy teaching and analyze the facilities and difficulties of its development in the graduation courses in nursing in Sao Paulo State. The data was collected in 40 institutions, where there were 76 participant professors. The results showed that the theme is approached in the programmatic content of Pediatric Nursing in most of these institutions, in the third, more effectively in the last ten years, both in the theoretical and practical teaching. The theoretical load time had a variation of one to 20 hours, using expositive and participative class and the written test prevailed in the theoretical evaluation strategies and in the practical, the students observation. Some difficulties and facilities mentioned refer to valorization and to infra structure favorable to these resources. PMID- 17340725 TI - [CIPESC Curitiba: the work of nursing at Bairro Novo District]. AB - Curitiba has been utilized system CIPESC--International Nursing Practice Classification in Collective Health. This study goal identifies the activities of nursing staff in the health units of Bairro Novo district of Curitiba City. We interviewed nursing and auxiliaries using check-list. The results showed: the sheltering is done by everyone; the auxiliaries' activities are procedures caring; all the nurses do nursing consultation and most of then use computer based system CIPESCO. In conclusion, excepting the research activities, the nursing staff works all the time according municipality program, such is under organized and scientific based system to giving nursing care, emphasizing at women health. Activities such as planning and education have been improved also. PMID- 17340726 TI - [Prevalence of chronic pain in adult workers]. AB - Chronic pain is a public health problem which causes personal and social losses. There are few epidemiological studies of chronic pain in Brazil and elsewhere in the world, especially those dealing with non-specific pain, in general population. The objectives of this study were: to identify the prevalence of chronic pain in adult workers; to analyze the prevalence of chronic pain according to gender, and local of pain. The sample was 505 workers at Londrina State University (Parana, Brazil) (estimated prevalence = 50%, 4% error, and confidence interval = 95%). Data were collected by interviews. The prevalence of chronic pain was 61.4%; and it was significantly higher among women (p = 0.0001). The most prevalent locals of pain were: head (26.7%), lower back (19.4%) and limbs (13.3%). PMID- 17340727 TI - [Changes in relationships with friends, husband and family after cancer diagnosis in women]. AB - The proposal of this research was to identify changes occurred in relationships after cancer diagnosis in the women. As a theoretical-methodological strategy it was utilized respectively the Symbolic Interacionism and the Grounded Theory. Ten women bearers of cancer and one familiar joined the research. We identify that occurred changes in the relationships with friends, the closest relations consolidated even more and the superficial ones did not exist. With the spouses, some of the relationship became better and others, that were already hard, faced a lot of problems even the separation. With the family the relationships became stronger The research allows us to understand a particular context of the woman with cancer and re-think some care strategies starting from these relations. PMID- 17340728 TI - [Practices used by women at post-birth on nipple problems]. AB - This is a qualitative study, of Convergent-assistential type, with the objective of knowing the women's practices at post-birth for the resolution of nipple problems, at home, and intervene to its resolution. Fourteen women at post-birth who were in the breastfeeding period and attended at a Center of Integral Attention to Health were participants. It was used a semi-structured interview, participant observation and notes in field diary, analised according to Trentini and Paim's proposal. The themes were the following: Practices used by the women with nipple problems; their repercussion and breastfeed ending and promotion of feeding. The diversification of products used by women at post-birth, the necessity of health professionals to know the practices used in the communities and be used in relation to breastfeeding, to its promotion, were the findings. PMID- 17340729 TI - [Nurse supervision in health basic units]. AB - This qualitative study intends to evaluate the pattern of supervision of the nurse in health basic units, in Feira de Santana city (Bahia-Brasil), between August 2001 and June 2002. The objective was to describe the supervision and the existence of supervision systematics for the nurse. A questionnaire was used to take informations from a group of sixteen (16) nurses in actual professional work. Descriptive statistical procedures for data analysis were used. It can be concluded that systematic supervision is practiced in 64% of the nurses and in 36% of the cases systematic supervision do not occur. PMID- 17340730 TI - [A brief reflection about integrality]. AB - The study aimed at exploring the knowledge of nurses about integrality in health, in such way to reflect about the interface of this principle in work relations. The research subjects were nurses from the basic health system of two counties of Rio Grande do Sul State. The data were collected by a questionnaire, beind coded in five categories for analysis: National Health System (NHS) of today, the principles of the NHS, the integrality of assistance, the integrality and its interface into the daily work of nurses and the integral with priority on the service. For the the respondents the NHS is a compete system in its principles and guidelines, howeverin reality it does not work as the legislation prescribes. The respondents percieve integrality as a priority in health practices. PMID- 17340731 TI - [Can breastfeeding promote acute pain relief in newborns?]. AB - This review study aimed to identify the efficacy of breastfeeding and its component aspects (contact, sucking, odor and milk) as nonpharmacological measures for pain relief in newborns. 14 articles from Medline/PubMed were analyzed. We observed methodological differences related to sampling, painful procedures, periods, treatment administration and variables measured. Breastfeeding and its component aspects were perceived as efficient to relieve acute pain. We observed the need for studies to evaluate the analgesic effect of breastfeeding before the painful procedure until recovery. This period is sufficient to achieve the analgesic effect after milk absorption. The interaction between all breastfeeding components must be considered. PMID- 17340732 TI - [Efficiency of health education programs for adults with high blood pressure]. AB - It is of great importance to acknowledge health education strategies nurses use on patients with high blood pressure, seeing how they respond and if the method is eficient for for them. The aim was to analise researches which focused on strategies to develop health education for adults with high blood pressure. This is a bibliography study which used data basis from MEDLINE. The abstracts found showed the folowing themes: high blood pressure, education and nursing. After the analisis two articles in english fitted in the established criteria. It was noticed that organized programes improve health conditions in factors such as high blood pressure risks and approval to the treatment given, being noticed a change of behavior and adherence to the drug treatment. PMID- 17340733 TI - [The costumer's satisfaction in the nursing assistance evaluation]. AB - This study detaches the importance of the perception of the customer in the process of evaluation of the nursing assistance. Through of bibliographical study research in the period understood between 1990 and 2004. This study reviewed on customer's satisfaction, where had been identified to concepts and publications that approached the perception of the customer as important factor in the evaluation of the nursing assistance. Thus, concluding, that customer has important paper in the attainment of the resulted real of the offered assistance, therefore characterizes as source of opinions and suggestions assisting in the process of evaluation. PMID- 17340735 TI - [Nursing care systematization in rehabilitation unit, in accordance to Horta's conceptual model]. AB - The utilization of a conceptual model in the Nursing Attendance Systemization allows the development of activities based on theoretical references that can guide the implantation and the implementation of nursing proceedings in hospitals. In this article we examine the option made for the implementation of the Horta's conceptual model in the construction of a nursing attendance system in the Rehabilitation Unit of a public hospital located in the Federal District of Brazil. Through the utilization of these theoretical references it was possible to make available a data collection tool based on the basic human needs. The identification of these needs made possible the construction of the hierarchically disposed pyramid of the neurological patients' modified basic needs. Through this reference paper we intend to elaborate the prescription and nursing evolution based in the concepts and standards of the Horta's nursing process, making possible the inter-relationship of all phases of this attendance methodology. PMID- 17340734 TI - [Historical, cultural and social aspects of labor]. AB - It is a historical-social study that aimed at contributing for the comprehension of the continuous evolution of the working process since the Classic Antiquity until the industrialization in the modern world and the intimate relation with the worker. A variety of bibliographic sources were used for this essay based on historical, conceptual, filosophical and scientific data. The findings drove to the conclusion that although deep transformations have occurred on the world of labor, the working activity, in its essence, has marked the lives of individuals and collectivities in different times and places. PMID- 17340736 TI - [Knowledge production: a dialogue among different knowledge]. AB - This text approaches the necessary dialogue among different knowledge and considers the advances within Nursing in the search for consistence and clarity within the Nursing discipline. Towards this end, the text is based upon transdisciplinarity, intersectorality, complexity, and the interaction of different pairs in health and other areas, as well as the sustainance of scientific and technological space within Nursing. It argues perspectives that open possibilities for scientific and technological knowledge construction within a more responsible and mutual social commitment. The purpose of the paperis to amplify the aptitude for contextualization and globalize different knowledge, as well as transcend differences and peculiarities within the perspective of more qualitative policies which may overcome disciplinary barriers. PMID- 17340737 TI - [The nursing team and Maslow: (dis)satisfaction in the work]. AB - This text tries to understand the Nursing team and their (dis)satisfactions in the work. We consider the association with the theory of basic human needs of Abraham Maslow as a way to systemize and to comprehend the recurrent situations and the day-by-day Nursing issues. The necessities are structuralized hierarchically in physiological, security, social, auto-esteem and auto accomplishment indicating the degree of satisfaction (from the disease to the fullness) of an individual or group. The advantage of this approach consists of being able to use the solid, depth and rich Maslow theory in concrete and particular situations of the Nursing team. PMID- 17340738 TI - [Technical evaluation as a competence of the nurse: reflections and pressupositions in the scenario of science and technology]. AB - This article approaches the concepts and presuppositions related to technical evaluation, through the use of equipment, inspired by the national system of science and technology. It shows the necessarily of the professional nurse to develop competencies such that, beginning with their formation, they are stimulated to interest themselves, create and participate in research projects. Today's universe is one of interdisciplinary influences, still little explored by professionals. The article has as it's goal to tontribute to the discussion of the management and technical assistance of a more humane nursing profession, marked by quality, efficacy, effectiveness and security. In this way guaranteeing positive results for those technologies, which were developed in the service of health. PMID- 17340739 TI - [Creation memory of the nursing undergraduate course at the University of Campinas]. AB - The objective of this study was to reconstitute the history of the creation of the Nursing Undergraduate Course at the Medical Sciences School, University of Campinas, occurred in 1978, through an unofficial history, due to the insufficiency of pertinent documental sources. Nurses who participated directly and actively in this process were the subjects of the research. The School of Nursing, legally planned since 1966, was never established. To answer to the minimum necessary organization, it was instituted only one Department of Nursing, four years after the beginning of the course. The interest and the initiative to establish the course started from a titled nurse, outside of the university, hired specifically for this purpose. This fact explains the personal trace, not very institutional, that characterized in a predominant way the moment of creation and continuity of this course. PMID- 17340740 TI - [The Kangaroo-Mother Method under the problem-solving look of a neonatal team]. AB - This article has as objective to tell the experience of the development of an educative process with a team of neonatal health, on the potentialities of the kangaroo-Mother Method in the assistance to the newborn and the family, from the theoretical methodological framework problem-solving. Twelve workshops were developed, aiming at providing to the group of professionals the chance to reflect on its reality, to analyze it of critical form, searching to understand it and to transform it. The results pointed the necessity of the creation of spaces with respect to reflections between the professionals of the neonatal team on practical its, making possible the transformation of the effective assistance model and favoring the integral and individuality care delivered to the newborn and to the family. PMID- 17340741 TI - Electroconvulsive therapy. With new methods and accumulated evidence, this treatment survives its critics. PMID- 17340742 TI - The social voice of conscience. PMID- 17340743 TI - Obesity and depression. PMID- 17340744 TI - Thwarting alcoholism in the brain. PMID- 17340745 TI - Questions & answers. I've been taking Zoloft. Recently, my pharmacist filled my prescription with a generic form of the drug. Does the brand name matter? PMID- 17340746 TI - Toward Alzheimer's prevention. PMID- 17340747 TI - Uncovering the benefits of aspirin. PMID- 17340748 TI - Easing the unwanted effects of chemotherapy. PMID- 17340749 TI - The ins and outs of outpatient procedures. PMID- 17340750 TI - Can you have a pain-free endoscopy? PMID- 17340751 TI - The analyst as eye doctor and as marine mammal specialist. PMID- 17340752 TI - A comment on "The case of Stevie". PMID- 17340753 TI - Life and death decisions: America's changing attitudes towards genetic engineering, genetic testing and abortion, 1972-98. PMID- 17340754 TI - Remaking ourselves? The ethics of stem-cell research. PMID- 17340755 TI - Politically incorrect abortion. Boys only. PMID- 17340756 TI - Federal funding of human embryonic stem cell research: an institutional examination. PMID- 17340757 TI - The reviving debate in eugenics: eugenics publications 2003-early 2005 and eugenics data bases. AB - Interest in medical procedures that will reduce genetically-induced diseases is increasing, even though reaction to any consciously directed program in eugenics remains strong. The author provides an extensive survey of recent publications and data bases that discuss various aspects of eugenics in the light of current scientific knowledge, medical technology and popular ethics. PMID- 17340758 TI - RNA interference: a critical analysis of the regulatory and ethical issues encountered in the development of a novel therapy. PMID- 17340759 TI - On: Analytic impasse and the third. PMID- 17340760 TI - On: Attachment theory and psychoanalysis. PMID- 17340761 TI - [Abstracts of the 50th Annual Meeting of the Japanese Society for Medical Mycology, Tokyo, Japan, October 21-22, 2006]. PMID- 17340763 TI - Sugar solutions. Interview by James Mitchell Crow. PMID- 17340764 TI - Probing expression. PMID- 17340765 TI - Triple-layer duct-to-mucosa pancreaticojejunostomy after pancreaticoduodenectomy. AB - BACKGROUND: Pancreaticoduodenectomy is associated with a high degree of morbidity; the main cause is failure of the pancreatic anastomosis. It is imperative that this is performed safely and is secure. Pancreatic leaks will lead to serious morbidity and even mortality. Here we describe the use of a new surgical triple-layer pancreaticojejunostomy in a group of patients with minimal morbidity. METHODS: This is a retrospective review from a prospective database. Fifty-one consecutive patients underwent a pancreaticoduodenectomy (either pylorus-preserving (PPPD) or classical Whipple's) from May 1999 to December 2005 and had the pancreaticojejunostomy reconstructed as described below. RESULTS: The mean age of the 51 patients was 56.71 +/- 9.0 years; 32 (62.7%) were female and 19 (37.3%) were males. The mean operating time was 368.55 +/- 57.94 min; the average blood loss was 396 +/- 236 ml with 15 patients (29.4%) requiring postoperative blood transfusions. The mean pancreatic duct size was 4.94 +/- 2.6 mm. In terms of pancreatic texture, there were 33 (64.7%) hard pancreas and 18 (35.3%) soft pancreas. PPPD was performed on 28 (54.9%) and the classical Whipple's procedure on 23 (45.1%). Twelve patients had postoperative complications; only 1 patient had a pancreatic fistula which was treated conservatively. CONCLUSION: This method is safe and reliable. It can be used for a myriad of pancreas remnants with a wide range of pancreatic duct sizes. PMID- 17340766 TI - Doctors and nurses of death: a case study of eugenically motivated killing under the Nazi 'euthanasia' programme. AB - This article reviews newly declassified US intelligence files and other sources, including relevant trial documents, related to the Nazi killing of mentally and physically sick individuals deemed to be of little further use to society. It both supplements and revises existing work on the so-called 'Euthanasia' programme at the Kaufbeuren psychiatric institution in Bavaria, and highlights a series of gender issues related to the involvement of women nurses including Catholic nuns, in this institute. In addition, this study not only casts new light on the way in which patients were, from admission onwards, redefined as disposable objects but also emphasises contradictions within the defence case of the defendants. PMID- 17340767 TI - Abstracts of the 2006 Canadian Society for Exercise Physiology Annual Scientific Conference, 1-4 November 2006, Halifax, Nova Scotia, Canada. PMID- 17340768 TI - Human genetic enhancements: a transhumanist perspective. PMID- 17340769 TI - Choosing between possible lives: legal and ethical issues in preimplantation genetic diagnosis. AB - This article critically appraises the current legal scope of the principal applications of preimplantation genetic diagnosis (PGD). This relatively new technique, which is available to some parents undergoing in vitro fertilization (IVF) treatment, aims to ensure that a child is not born with a seemingly undesirable genetic condition. The question addressed here is whether there should be serious reasons to test for genetic conditions in embryos in order to be able to select between them. The Human Fertilisation and Embryology Authority and the Human Genetics Commission have decided that there should be such reasons by broadly aligning the criteria for PGD with those for selective abortion. This stance is critically explored, as are its implications for the possible use of PGD to select either against or for marginal features or for significant traits. The government is currently reviewing the legal scope and regulation of PGD. PMID- 17340770 TI - Synthesis and pharmacology of glutamate receptor ligands: new isothiazole analogues of ibotenic acid. AB - The naturally occurring heterocyclic amino acid ibotenic acid (Ibo) and the synthetic analogue thioibotenic acid (Thio-Ibo) possess interesting but dissimilar pharmacological activity at ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs). Therefore, a series of Thio-Ibo analogues was synthesized. The synthesis included introduction of substituents by Suzuki and Grignard reactions on 4-halogenated 3-benzyloxyisothiazolols, reduction of the obtained alcohols, followed by introduction of the amino acid moiety by use of 2 (N-tert-butoxycarbonylimino)malonic acid diethyl ester. The obtained Thio-Ibo analogues (1, 2a-g) were characterized in functional assays on recombinant mGluRs and in receptor binding assays on native iGluRs. At mGluRs, the activity at Group II was retained for compounds with small substituents (2a-2d), whereas the Group I and Group III receptor activities for all new compounds were lost. Detection of NMDA receptor affinity prompted further characterization, and two-electrode voltage-clamp recordings at recombinant NMDA receptor subtypes NR1/NR2A-D expressed in Xenopus oocytes were carried out for compounds with small substituents (chloro, bromo, methyl or ethyl, compounds 2a-d). This series of Thio-Ibo analogues defines a structural threshold for NMDA receptor activation and reveals that the individual subtypes have different steric requirements for receptor activation. The compounds 2a and 2c are the first examples of agonists discriminating individual NMDA subtypes. PMID- 17340771 TI - Abstracts of the 47th Annual Conference of the Indian Society of Gastroenterology in association with the Indian National Association for the Study of the Liver and the Society of Gastrointestinal Endoscopy of India, November 8-12, 2006, Mumbai, India. PMID- 17340773 TI - Abstracts of the 10th Jubilee International Congress of the Polish Cardiac Society, Gdynia-Sopot-Gdansk, 21-23 September 2006. PMID- 17340772 TI - Reclaiming "abandoned" DNA: the Fourth Amendment and genetic privacy. PMID- 17340774 TI - The Self-Care Self-Efficacy Enhancement Program for Chinese nursing home elders. AB - The purpose of this article is to introduce a theory-based intervention program, the Self-Care Self-Efficacy Enhancement Program (SCSEEP), which was derived from Bandura's Social Cognitive Theory (SCT). The SCSEEP, based on the concept of "perceived self-efficacy" within the SCT, was designed to improve self-care ability in Chinese nursing home elders. The theory-based SCSEEP was tested during a pilot study involving 42 elders from 2 nursing homes in Taiwan. Following the study, basic activities of daily living performance improved significantly in treatment group residents. Many Chinese elders are placed in nursing homes in the United States; thus, the SCSEEP may also be used as a theory-based caring model to improve self-care performance in Chinese Americans. PMID- 17340775 TI - Advance practice nursing and sexual functioning in late life. PMID- 17340777 TI - [Abstracts of the 181 Meeting of the Rheinisch-Westfalischen Society of Internal Medicine, Essen, 1-4 November 2006]. PMID- 17340776 TI - Contribution of the IBD5 locus to Crohn's disease in the Swedish population. AB - OBJECTIVE: Recent data have controversially suggested that variants of the organic cation transport genes SLC22A4 (OCTN1) and SLC22A5 (OCTN2) are responsible for the contribution of IBD5 to disease susceptibility in Crohn's disease (CD). The objective of this study was to assess the contribution of the SLC22A4 variant (1672T) and SLC22A5 variant (-207C) together with three IBD5 haplotype markers in the previously uninvestigated Swedish CD population. MATERIAL AND METHODS: The study comprised 178 CD patients and 143 healthy controls (HC). Genotyping for IBD5 single nucleotide polymorphisms (SNPs) IGR2096a_1, IGR2198a_1, IGR2230a_1, SLC22A4 1672T and SLC22A5 -207C was carried out using the TaqMan system. Associations with disease susceptibility and disease phenotype were investigated. RESULTS: Strong linkage disequilibrium was observed between the investigated SNPs (D prime >0.92). IGR2096a_1 allelic frequency and homozygosity rates were associated with CD (44% CD versus 33.8% HC, p=0.008, OR=1.55 and 20% CD versus 12% HC, p=0.04, OR=1.93, respectively). Variant allelic frequency of SLC22A4, 1672T (44% versus 36%, p=0.03, OR=1.4) and homozygosity for the SLC22A4, SLC22A5 TC haplotype (1672T, -207C) (21.3% versus 12%, p=0.03, OR=1.78, population attributable risk (PAR)=11%) were associated with CD. There was no association between the allelic frequency of SLC22A5 and CD (46.6% CD versus 41.5% HC, p=0.82). The association of the TC haplotype with CD was not independent of the SNPs representing the extended IBD5 linkage interval. CONCLUSIONS: The IBD5 locus is associated with CD in the Swedish population. The strongest association is with the marker SNP IGR2096a_1, lying p-telomeric to SLC22A4 and SLC22A5. The effect of the TC haplotype was not an independent determinant in this population. PMID- 17340779 TI - A natural selection. PMID- 17340778 TI - The rise and rise of green chemistry in China. Interview by Nicola Nugent. PMID- 17340780 TI - Abstracts of the 36th Annual Meeting of the German Society for Thoracic and Cardiovascular Surgery, February 11-14, 2007, Hamburg, Germany. PMID- 17340782 TI - [Abstracts of the 29th Congress of the Polish Society of Physiopneumonology, Opole, 2006]. PMID- 17340781 TI - [Abstracts of the 69th National Congress of the Italian Society of Occupational Medicine and Industrial Hygiene (SIMLII), Montesilvano, Italy, 26-28 October 2006]. PMID- 17340783 TI - Abstracts of the VEITHsymposium, November 14-18, 2007, New York, New York, USA. PMID- 17340784 TI - Tracking trends in Canadian gastroenterology research. Interview by Paul C. Adams. PMID- 17340785 TI - The use of race in medicine as a proxy for genetic differences. AB - Race is a prominent category in medicine. Epidemiologists describe how rates of morbidity and mortality vary with race, and doctors consider the race of their patients when deciding whether to test them for sickle-cell anemia or what drug to use to treat their hypertension. At the same time, critics of racial classification say that race is not real but only an illusion or that race is scientifically meaningless. In this paper, I explain how race is used in medicine as a proxy for genes that encode drug metabolizing enzymes and how a proper understanding of race calls into doubt the practice of treating race as a marker of any medically relevant genetic trait. PMID- 17340786 TI - The fate of stem cell research and a proposal for future legislative regulation. PMID- 17340787 TI - [Post-resuscitation stabilization and transportation]. AB - Cardiopulmonary resuscitation does not end with restoration of spontaneous circulation; rather, it must be continued with the application of all the measures that allow organ function to be maintained. The initial goal of hemodynamic treatment is to achieve normal blood pressure for the patient's age by means of fluids and/or vasoactive drugs. The aim of respiratory treatment is to normalize ventilation and oxygenation without causing further lung injury, avoiding hyperoxia and hyperventilation as well as hypoxia and hypercapnia. Neurological stabilization aims to reduce secondary brain damage, by avoiding hypertension and hypotension, maintaining normal ventilation and oxygenation, and treating hyperglycemia, agitation and seizures. Although no specific studies in children are available, data from adults have shown that early moderate hypothermia attenuates brain damage secondary to cardiorespiratory arrest, without increasing complications. After the arrest, the need for analgesia and/or sedation must be considered. The process of transportation to the pediatric intensive care unit (PICU) requires the following steps: stabilizing the patient, checking for and stabilizing fractures and external wounds, ensuring a stable airway and intravenous lines, assessing the need for nasogastric and bladder tubes, taking blood samples for analyses, contacting the PICU and informing the staff about the child's condition, choosing the optimal vehicle for transportation according to the child's condition and the distance, checking pediatric equipment and medications, selecting experienced staff and, finally, maintaining close surveillance and monitoring during transportation. PMID- 17340788 TI - [Initial pediatric trauma care and cardiopulmonary resuscitation]. AB - Accidents are a frequent cause of death in children older than 1 year. The most frequent causes of death by accident are traffic accidents, drowning, intentional injuries, burns, and falls. Cardiopulmonary resuscitation is one component of the set of actions needed to obtain initial stabilization of a child with serious trauma. In the first few minutes after the accident, cardiorespiratory arrest can occur due to airway obstruction or inadequate ventilation, massive blood loss or severe brain damage; cardiorespiratory arrest in this setting has a dismal outcome. When arrest occurs hours after trauma, it is usually caused by hypoxia, hypovolemia, hypothermia, intracranial hypertension, or electrolyte disturbances. The first response to trauma should include three objectives: to protect (scenario assessment and implementation of safety measures), to alert (activation of the emergency medical system) and to help (initial trauma care). Initial trauma care includes primary and secondary surveys. The primary survey involves several consecutive steps: A. airway and cervical spine stabilization, B. breathing, C. circulation and hemorrhage control, D. neurological dysfunction, and E. exposure. The secondary survey consists of assessment of the victim by means of anamnesis, sequential physical examination (from head to limbs) and complementary investigations. During emergency trauma care, specific procedures such as extrication and mobilization maneuvers, cervical spine control by means of bimanual immobilization, and cervical collar placement or helmet removal. If a cardiorespiratory arrest occurs during initial trauma care, resuscitation maneuvers must be immediately started with the specific adaptations indicated in children with trauma. PMID- 17340789 TI - Bibliography. Current world literature. Crystal deposition diseases. PMID- 17340790 TI - Bibliography. Current world literature. Rehabilitation medicine in rheumatic diseases. PMID- 17340791 TI - [Wounds, Wound Infections, and Early Postoperative Complications in Abdominal and Vascular Surgery. Scientific-Practical Conference with International Participation. Abstracts. December 14-15, 2006, Kyiv, Ukraine]. PMID- 17340792 TI - Sugar solutions. Interview by James Mitchell Crow. PMID- 17340793 TI - Probing expression. PMID- 17340794 TI - [Study on serum and urine concentrations of erythromycin succinate of pyrrolidine methyl-tetracycline]. AB - The serum and urine antibiotic levels in a group of 25 patients were determined after a single administration of a new antibiotic salt: erythromycin succinate of pyrrolidine-methyl-tetracycline. Some subjects were treated orally and other intramuscularly. The results obtained showed that this drug gives, both orally and intramuscularly, efficient serum and urine concentrations of tetracycline and erythromycin. PMID- 17340795 TI - [A roentgenologic study on metoclopramide in the vagotomized rat]. AB - After a brief description of the central pharmacodynamic action of metoclopramide, the results of an investigation in two groups of rats of the same age, sex, and weight are reported. The first group was subjected to vagotomy, whereas the second consisted of normal animals. The experiment consisted of two stages. During the first part of the experiment control roentgenograms were taken at fixed intervals after a barium solution had been introduced into the stomach of the animals (both normal and vagotomized). Later, the experiment was repeated after the intravenous or intramuscular administration of 5 mg of metoclopramide. A positive action of Plasil on the gastro-intestinal motility was confirmed in the normal rat, as was the negative action of the drug in the vagotomized animal. An effective action of the drug on the gastro-intestinal system thus depends on the integrity of the efferent parasympathetic paths; this is probably also related to species differences. PMID- 17340796 TI - [Antepartunm radiological diagnosis of achondroplasia]. AB - On the basis of personal case reports, the possibility of an antepartum radiological diagnosis of achondroplasia is discussed and its value and limits are underlined. PMID- 17340797 TI - [The influence of kanamycin, viomycin and ethambutol on the process of healing in experimental surgical wounds]. AB - Experimentation of the action of kanamycin, viomycin and ethambutol in wound healing is reported. The planimetric measurement system of Carrel-Lecomte du Nouy was used to determine the development of the cicatrisation process. Prolongation of healing times in the 3rd and 4th periods is demonstrated and attributed to the general toxic action of these drugs, combined with direct toxic interference with epithelization and cicatrisation. PMID- 17340799 TI - [Peculiar chromosomal pattern in a case of acute myeloblastic leukaemia in a patient with XY/XO mosaic]. AB - The results of chromosomal studies in a patient with XY/XO mosaic and acute myeloblastic leukaemia are presented. The onset of leukaemia was associated with a further chromosomal anomaly consisting in the loss of a small group G acrocentric. PMID- 17340798 TI - [The median sacral artery in the human adult]. AB - The topographical projection, course and length of the median sacral artery were studied in 32 adults. It was found that the artery originates at the lower quarter of the 3rd lumbar vertebral body and that its craniocaudal path does not coincide with the median sagittal plane of the lumbosacral column. Artery length values were in line with those reported by other workers. PMID- 17340800 TI - [A contribution to the study of cardiac lipofuscin fluorescence]. AB - Some characteristics of the fluorescence of cardiac human lipofuscin and, in connection, the acid phosphatase activity were studied. The presence of acid phosphatase reaction product was demonstrated in lipofuscin granulations. Two types of fluorescence spectra with a maximal emission peak at 580 nm. and 600-610 nm. respectively, were obtained. A photodecomposition of average intensity was present and, at same time, shifts the maximal emission peaks were noticed. The data obtained were discussed in relation with the identification of the fluorescent substance. PMID- 17340801 TI - [Medical and social problems raised by infantile diabetes]. AB - Recent clinical and statistical data are referred to in an account of the medical and social problems raised by diabetes in infancy and attention is placed on modern methods employed in the management of this disease. An examination is also undertaken of problems facing young patients with respect to their family, scholastic and later professional life. PMID- 17340802 TI - [Experimental hormonal carcinogenesis]. AB - Experimental carcinogenesis associated with estrogen and progesterone treatment in the induction of mammary tumours and reported in the literature is discussed. The various investigations are compared and some theories are advanced. Techniques for the induction of ovarian tumours and tests carried out with steroids as anticarcinogenic competitive substances are reviewed. Both increased (nucleotidase, aminopeptidase) and decreased (alkaline phosphatase) enzyme values were observed in the case of estrogen induced cervicovaginal neoplasia in the ovariectomised rat. PMID- 17340803 TI - [The medical and social aspects of progressive muscular dystrophy]. AB - The existing medical and social patterns of myopathy, in particular progressive muscular dystrophy, are discussed. Attention is drawn to the relative high frequency of this disease, its seriously incapacitating consequences and its hereditary and progressive nature. Reference is made to the work being done abroad and in Italy to cope with this problem and an account is given of questions concerning prophylaxis and, in particular measure, the steps being taken to rehabilitate sufferers from this disease and to offer them the chance of leading a useful social and working life. To this end, physio-kinesitherapy and training in modern clinical and professional education centres are employed. PMID- 17340804 TI - [Medical and sociologic problems in laryngectomy]. AB - Laryngectomy, especially radical destructive laryngectomy, as still often performed for cancer of the larynx, undoubtedly leads to various medico sociologic, hygienic-prophylactic, and socio-economic problems of the greatest interest. The need for adequate psychologic preparation, for the adoption of essential hygienic rules, and for re-training of the voice is stressed by the fact that this type of patient can be effectively recuperated since surgical treatment can attain a permanent cure in a high proportion of cases. These subjects can therefore be reinserted in society at a definitely profitable level. PMID- 17340805 TI - [Development, configuration and structure of the temporal fascia in humans]. AB - The genesis, configuration and structure of the temporal fascia in humans, during the various stages of fetal development and in the adult were studied in order to contribute to the knowledge of its morphological and topographical characteristics. The most remarkable results are: (1) In the adult, there is a thin connective laminar layer interposed between the "galea capitis" and the temporal fascia, derived from the deep subcutaneous layer; (2) the temporal fascia develops about the third month of intra-uterine life and is well outlined at the fourth month. In this period it seems to be subdivided, in its lower third, into two layers (superficial and deep) reaching the zygomatic arch and circumscribing a triangular space in the frontal sections, originally occupied by loose connective tissue and then, beginning from the fifth month, by fatty tissue; (3) the two uncoupling or unlaminar layers of the temporal fascia in the adult join the lateral surface of the zygomatic arch; (4) from the end of the fifth fetal month, an accumulation of primary fat is interposed between the temporal m. and its fascia: this is to be interpreted as a temporal extension of the Bichat's fat-ball in the cheek. PMID- 17340806 TI - [An uncommon anatomical variety of the right lower apical bronchus]. AB - A rare (1 case out of 1000 bronchoscopies) variety of the right lower apical bronchus, consisting in its division into two bronchi, one emerging from the intermediate bronchus and the other situated one centimeter lower, in front of the orifice of the middle lobar bronchus, is described. PMID- 17340807 TI - [Histochemical demonstration of glial enzyme activity. I. Normal glia]. AB - The literature data for normal glia enzyme activity are reviewed, with special reference to the specific phosphatases and the nucleoside-phosphatases and their relationship to transport mechanisms and the Golgi apparatus. Their demonstration still presents technical difficulties and is also hindered by substrate affinity variations which influence the histochemical picture; greater activity is sometimes observed in the oligodendrocytes and sometimes in the astrocytes and, in the latter, in different cytoplasma or nucleus structures. Using 32ATP, Hyden has shown the importance of this enzyme as a regulator of neuron K availability and of substrate transport from the capillaries to the nerve cells. Several workers have shown the striking positivity of the ATPase reaction in animal glia, as well as its importance in the sodium pump mechanism. Carboanhydrase is also involved in transport mechanisms. Giacobini has demonstrated high cholinesterase values and an absence of AChE in oligodendrocytes and astrocytes. Lysosome has been proved to be an arylsulphatase site. Phosphorylase is important in glial cell metabolism, since high levels indicate increased glycogen metabolism. PMID- 17340808 TI - [Histochemical demonstration of glial enzyme activity. II. Reagent and neoplastic glia]. AB - Enzyme activity changes in reagent and neoplastic glia are examined. In the case of reagent glia, considerably increased ADPase, ATPase and AMPase values have been observed in experimental elective parenchymal necrosis in the rat, in hypertrophic astrocytes from recent plaques in multiple necrosis, in demyelinisation associated with cyanide encephalopathy, and in reagent astrocytes surrounding tumours and arteriosclerosis sites. Depressed ATPase values have been observed in experimental oedema, as compared with increased TPPase in human oedema. BuChE and ChE activity disappears in both oligodendro- and astroglia near old cerebral infarct sites, whereas there is marked BuChE activity peripherally to multiple sclerosis plaques and in areas of phenylpyruvic oligophrenia demyelinisation. In neoplastic glia, ADPase is clearly evident in malignant gliomas, ATPase is related to the extent of the cell body, AMPase is positive in medulloblastoma cell cytoplasm and beta-glucuronidase increases in anaplasia. Above-normal ChE activity has been observed in astrocyte tumors, while BuChE is greater than that of AChE. Phosphorylase reaction is intense in astrocytoma and in glioblastoma giant cells. Phosphoglucomutase values are below-normal in tumours, except in the case of ependymoma, while both phosphohexoisomerase and hexokinase display increased activity in atypical forms. PMID- 17340809 TI - [Contribution to the clinical study of renal haemodynamic changes due to histamine: considerations on some pathogenetical stages of shock]. AB - This investigation was undertake to study some of the renal haemodynamic changes produced by istamine in the man. Experiments were carried out on ten adult subjects and histamine (20 gamma) was injected intravenously. The diuresis, the glomerular filtration and the plasmatic kidney output decrease during the fifteen minutes succeeding the injection and the recovery was complete thirty minutes after histamine. Because no changes in heart rate and blood pressure were observed after the histamine injection the renal vasocostriction may perhaps act initially to antagonize the hipotensive effects of this drug. PMID- 17340810 TI - [Serum protein, particularly immunoglobulin, behaviour in 130 aged subjects]. PMID- 17340811 TI - [Renal excretion of phosphates in humans during the various phases of growth]. AB - Blood phosphorus and P.E.I. values were determined in 54 subjects aged 3 to 19 yr and compared with those observed in 39 adults. Significant increases in tubular reabsorption of phosphorus and in blood phosphorus values in the firts group, primarily evident in the 6-13-yr-olds and gradually lessening after the age of 14 yr, are attribued to the action of HGH. PMID- 17340812 TI - [Recent progress in the stimulation of the histiocyte system and the anti infection defences. Research into the effect of stanozolol treatment on the phagocyte activity of human macrophages]. AB - A group of patients was treated with stanozolol. A modified version of Roebuck's skin window technique was used to obtain macrophages. These were then fixed in vitro with a suspension of Paracolonbacter aerogenoides. Comparison with a group of control subjects showed that the macrophages from the treated patients appeared to take up and destroy germs more effectively and that this could be potentiated by prior opsonisation with serum from the treated subjects. These results are seen as an expression of functional activation of the macrophages and an increase in serum opsonin content. PMID- 17340813 TI - [Antiadenovirus antibodies in mother-foetus serum pairs]. AB - The behaviour of E.A.I. antibodies towards 3 strains of adenovirus was investigated in 90 mother-foetus serum pairs. Considerable circulation of the studied antigens (9, 10 and 13) was observed; antigen 13 has so far been little associated with morbid syndromes. PMID- 17340814 TI - [Biliary elimination of N1,N1-diethyleniminobiguanido-methyl-tetracicline in humans]. AB - The investigations were carried out on 50 patients of both sexes, divided into 2 groups. The first group was formed by 30 patients, suffering from cholelithiasis, who underwent cholecystectomy. Half of these subjects were administered Xantociclina by oral route 5 hours before the operation, while the other half orally received an equivalent dose of tetracycline HC1. The antibiotic levels found in the bile taken during the operation, showed to be markedly higher after Xantociclina administration; the statistical analysis of the values obtained pointed out a most significant difference. The second group was formed by 20 patients suffering from acute cholecystitis; x-rays investigations had pointed out an obstruction of the gallbladder. In these subjects, divided into 2 groups of 10 each, and treated in the same way as those whose cystic ducts were free from obstruction, the antibiotic activity was determined not only in the bile but also in the homogenate of the gallbladder tissue. Markedly higher antibiotic concentrations were found after treatment with Xantociclina, both in the bile and in the gallbladder tissue homogenate. On the basis of the results obtained, the Authors maintain that the new antibiotic derivative can be usefully employed for the treatment of acute and chronic biliary disorders. PMID- 17340815 TI - [Biological premisses and therapeutic effect of immunological treatment with antilymphocytic globulin via the coeliac artery in hepatitis of immunological origin]. AB - The morphology of organ transplant rejection indicates that the circulation biophysics of the immunocompetent cells in the transplant capillaries is one of the most aspects of immune reaction haemodynamics. In the same way, the compromise of the liver-spleen arterial circulation observed in hepatitis of immunological origin may be interpreted on the basis of the spread of cellular aggregates, primarily lymphocytes whose reduced electrophoretic mobility is due to their being immunised with respect to the hepatic antigen. An immunological treatment, consisting of the perfusion of the liver with antilymphocyte globulins and other additives via the coeliac artery with the object of modifying the complex physico-chemical changes in the disturbed immunological dynamics, was carried out in 3 cases of hepatitis. The therapeutic results and their evaluation via a number of functional parameters are discussed. PMID- 17340816 TI - [Comparative evaluation of the influence of some steroids on plasma ACTH levels]. AB - Comparison was made between the biological activity of a synthetic polysteroid preparation and that of its individual constituents using the increase in plasma ACTH following the pituitary suppression caused by the administered substance as an index. The results showed that the preparation has a more significant influence on ACTH secretion than the other experimented products. PMID- 17340817 TI - [The action of gastric mucoprotein in experimental ulcers]. AB - Experimentally-induced ulcers in the dog (phenylquino!incarbonic acid) and in the rat (ligature of the pylorus, constriction) were treated with 20 mg/kg per day (dog) and 20 mg per animal per day (rat) of mucoprotein. The protective action excercised by this substance was demonstrated by increases in mean survival times and by the failure to apear, or by the more rapid regression, of lesions in the treated animals. PMID- 17340818 TI - [Protidogram and serum agglutinin data in rabbits subjected to vaccination and gastric mucoprotein administration]. AB - A statistical assessment was made of the results obtained in a study of the behaviour of the protidogram and serum agglutinins in rabbits subjected to Salmonella typhi murium vaccination and 25 and 50 mg/kg per day gastric mucoprotein. Albumin values were decreased in animals both vaccinated and treated, moderately increased in those that received mucoprotein only. Globulins increased in both groups. Antibody increases were most marked in animals vaccinated and treated with the larger mucoprotein dose. PMID- 17340819 TI - [Lymphangiography in the diagnosis of chronic pancreatitis]. AB - Numerous techniques exist for the biological and instrumental detection of chronic pancreatitis. Attention is here given to lymphangiography as a means of illustrating changes in lymph dynamics and node morphology, especially in the retro- and peripancreatic regions. A brief account of the technique is followed by the placing of more particular stress on the adoption of a variant whereby an inguinal route is preferred to a limb collector. Some conclusions are then offered with respect to the findings that can thus be obtained and their significant contribution to the differential diagnosis of chronic pancreatitis. PMID- 17340820 TI - [Lactic acid dehydrogenase in the diagnosis of rheumatic carditis]. AB - The literature relating to the determination of lactic acid dehydrogenase and its isoenzymes in the diagnosis of active rheumatic carditis is examined. It is noted that LDH values are normal in inactive chronic rheumatic valvulopathy and in non rheumatic cardiac insufficiency and that they are of much greater diagnostic utility than SGOT levels in cases of active rheumatic carditis. PMID- 17340821 TI - [Dysontogenetic cysts of the spleen]. AB - The classification of splenic cysts and the uncertainties surrounding this topic are discussed. Note is taken of the distinction between parasitic and non parasitic cysts, special reference being made to dysontogenetic pictures presenting as dermoid and epidermoid cysts, associated with dermo-opidermal inclusions in the splenic tissue. The histological, clinical and diagnostic features of such cysts are explained and some opinions are put forward with respect to their treatment. PMID- 17340822 TI - [Bone metastases of breast cancer]. AB - An account is given of the more common sites of bone metastasis in advanced breast cancer and of the tumour diffusion routes. The pathogenetic problem presented by the appearance of late metastases is then discussed. The histological picture and some typical clinical aspects of bone metastasis are described and an examination is made of the most recent endocrine, surgical and medical forms of treatment. PMID- 17340823 TI - [Respiratory function in atheromatous arteriosclerosis]. AB - VC, MEVS and Tiffeneau index values were studied in patients with atheromatous arteriosclerosis. Pronounced subnormal levels, directly proportional to the degree of atheroma, were observed. These are attributed to flow variations due to reduction of the calibre of the bronchial arteries. PMID- 17340824 TI - [Respiratory function in subjects with diabetes and atheromatous arteriosclerosis]. AB - VC, MEVS and Tiffeneau index values were studied in diabetic patients with atheromatous arteriosclerosis and compared with those observed in an earlier series where obliterating sclerosis was not complicated by diabetes. Further deterioration of values in the later series is attributed to the presence of diabetes. PMID- 17340825 TI - [Cystoid pneumatosis of the colon]. AB - Reference is made to the relatively low frequency of the colon as a site for pneumatosis cystoides intestinalis. It is noted that the condition, formerly diagnosed almost solely intraoperatively or at necropsy, can now be demonstrated by means of radiography, sigmoidoscopy and sigmoidoscopic biopsy in many cases. Some remarks concerning treatment are put forward and the possibility of spontaneous regression is noted. PMID- 17340826 TI - [Modern concepts concerning the hereditability of chromatic vision changes]. AB - Chromatic vision changes are examined and stress is laid on the different types and subtypes, and their distribution in various populations and racial groups. Some views are expressed concerning the genetic significance of these pictures as drawn from the listing of certain particularly demonstrative features. PMID- 17340827 TI - [The embryology and pathogenesis of congenital anophthalmus]. AB - The picture presented by congenital anophthalmus is presented and its primary, secondary and degenerative forms are distinguished. The frequency of this rare abnormality is discussed with reference to the literature data, both clinical and experimental, and the possible part played by various physical, chemical, infectious and genetic factors is explained. Some considerations are expressed concerning the qualitative and chronological mechanisms of action and the harmful factors responsible for this embryopathy. PMID- 17340828 TI - [Pathogenetic, clinical and therapeutical features of ophthalmologic involvement in Basedow's disease]. AB - A review of the recent literature concerning the pathogenetic, anatomical, pathological, clinical and therapeutical features of endocrine ophthalmopathy serves to lay stress on the fact that, whereas ocular signs are predominantly associated with hyperthyroidism pictures, they may also be encountered in other dysendocrinopathies. Satisfactory local and general treatment can be significantly improved by cooperation between the oculist and the endocrinologist. PMID- 17340829 TI - [Medical and social aspects of the question of noise in hospitals]. AB - An analysis is made of the part played by noise in modern life and attention is drawn to its harmful effects from the social point of view. An account is given of the essential principles of acoustics and of the main effects of noise on human physiopathology. Attention is then given to the specific question of the effect of both internal and external noise on both patients and staff in hospitals. Principles to be applied in the rational prevention of disturbances due to noise are suggested and stress is laid on the importance of improved social and health education in this respect. PMID- 17340830 TI - [Four cases of dissecting aneurysm of the aorta]. AB - Four cases of dissecting aneurysm of the aorta are described. Attention is drawn to the difficulties of clinical diagnosis, the results of which will often be expressed in wide differences of prognosis and sometimes of treatment pattern, including surgical correction in suitable cases. A summary account of the literature data is used in expressing some views on the clinical and aetiopathogenetic position in the light of recent knowledge. PMID- 17340831 TI - [Effects of X-rays on cells of ascites hepatoma in the rat. Immunoelectrophoretic researches]. AB - The effect of X-rays on the protein fractions of epatoma ascites tumor cells, has been investigated by free electrophoresis and immunoelectrophoresis methods. The irradiation cause changes in protein fractions with consequent modifications of their antigenic structures. PMID- 17340832 TI - [Urinary lacticodehydrogenase activity in the normal and hypertensive subject, in glomerular tubule disease, and in renal and vescical cancer]. AB - Urinary lacticodehydrogenase activity was determined in normal subjects and the results were compared with those observed in the more common renal diseases, in kidney and bladder tumours, and in arterial hypertension without nephropathic complications. A constant and well-defined increase was note in all serious diseases forms, particularly in tumours. Hypertension per se, however, was not accompanied by changes in normal enzyme excretion. Processing of the data indicated that this test might be of assistance in routine examinations for serious urinary diseases, especially cancer. PMID- 17340833 TI - [Determination of anti-O-streptolysin with polystyrol latex]. AB - Comparison is made between the results obtained with a new method for the determination of serum ASO titres based on rapid agglutination on slides with the use of polystyrene latex and those given by the classic haemolytic method. A virtually complete correspondence was observed between the two techniques and it is suggested that the new test be employed as a preliminary screening measure in the determination of serum ASO titres. PMID- 17340834 TI - [Microspectrophotometric determination of human leucocyte DNA content in vitro after irradiation]. AB - Microspectrophotometry was used to determine the DNA content of leucocytes cultured in vitro after irradiation. DNA content values ranges are interpreted as showing the presence of cells with a high ploidy and an increase in the number of cells in G2 stage. These findings are seen as an expression of the arrest of mitosis, without interfering with the duplicative capacity of DNA. PMID- 17340835 TI - [Microspectrophometric evaluation of DNA as a means of analysis of human leukocyte in vitro proliferative kinetics]. AB - Microspectrophotometric determination of in vitro human leucocyte DNA content, with or without PHA stimulation, is reported. The results obtained are compared with those observed with tritiated thymidine and their parallel pattern makes in clear that DNA microspectrophotometry can be employed in the study of proliferative kinetics. PMID- 17340836 TI - [Appearance of proliferative activity in peritoneal macrophages cultured in vitro. Mitotic index values and percent frequency of frequency of mitosis phase]. AB - In vitro culture of rat peritoneal macrophages, cells generally considered devoid of proliferative activity, was found to lead to the appearance of mitosis. Mitotic index and percent phase incidence values were determined for these cells. PMID- 17340837 TI - [Appearance of proliferative activity in peritoneal macrophages cultured in vitro. Stathmokinetic index and proliferative volume]. AB - In the course of further studies of mitotic activity in vitro cultures of rat peritoneal macrophages, an increment in proliferative volume between the 2nd and 6th day was observed, followed by a decrease. The relationships between these variations and those of the mitotic index (previously reported) are discussed. PMID- 17340838 TI - [Appearance of proliferative activity in peritoneal macrophages cultured in vitro. Karyokinetic chronology and phases]. AB - Contrast phase microscopy was employed to determine mitosis phase duration values in rat peritoneal macrophages in which proliferative activity had appeared following culture in vitro. Mitosis duration values were considerable and tended to increase in function of increases in culture time. These data are discussed in a general account of in vitro reproductive activity in peritoneal macrophages. PMID- 17340839 TI - [Cytomorphology and enzymocytochemistry of Coxsackie virus A9 infection in cell cultures]. PMID- 17340840 TI - [Pyogenic, syphilitic and tubercular infection of the theca cranica]. AB - The aetiological, anatomopathological, clinical and therapeutic aspects of pyogenic, syphilitic and tubercular infections the bones of the theca cranica are discussed and some personal cases are illustrated. It is held that medical treatment should be the first line of attack, surgical management being reserved solely for intractable forms. PMID- 17340841 TI - [Histological examination of renal lesions associated with hepatic cirrhosis in young subjects]. AB - Histopathological findings obtained by means of various methods in 8 cases of nephropathy, some in association with liver disease and some presenting as neonatal forms, are described. Extensive reference to the literature and to the pathogenetic hypotheses that have been advanced, particularly with respect to the possible action of autoimmunological factors, is followed by a comparative analysis of the presentt findings with those of other workers; the uniformity of the glomerular lesions observed in all cases seen at necropsy is made the basis for some suggestions concerning the genesis of renal lesions themselves. PMID- 17340842 TI - [Serum glycoproteins in hypertension]. AB - The plasma glycoprotein level was determined in 90 hypertensive patients, 20 of whom had myocardial infarctions and 18 cerebral haemorrhages or thromboses. An increase of the beta-glycoproteins was found. In the patients with infarctions of cerebral lesions the alpha2 fraction was also increased. An analysis of the findings suggests that an increase of the 3-glycoproteins is an unfavourable prognostic factor and is greatest in patients with evidence of atherosclerosis. PMID- 17340843 TI - [Sterilisation of anaesthesia and mechanical ventilation apparatus]. AB - Anaesthesia and mechanical ventilation apparatus is commonly the source of germs and a means for the transmission of serious forms of infection. Such infections have two main points of origin: the patient himself via the respik ratory passages, and the non-sterile ambient air of the hospital. The serious difficulties presented by the complete sterilisation of such equipment are discussed, these being due both to the size of the apparatus itself and the special needs of the material of which it is composed, and three different methods are put forward, each of which employs a different substance, namely: glyceraldehyde, ethylene oxide and formalin vapours. PMID- 17340844 TI - [A case of long-standing Weber-Christian panniculltis with visceral sites]. AB - A summary review of the relevant literature is followed by the presentation of a case of recurrent, febrile Weber-Christian-type nodular panniculitis with an unusual course. The patient, a young woman, presented not only the typical subcutaneous lesions and constant hyperpyrexia but also visceral signs resulting in frequent and sometimes considerable haematuria and intestinal haemorrhage. The skin and visceral signs had tended to alternate and had run without remission for over 10 years. Every form of treatment attempted had been found ineffective. PMID- 17340845 TI - [A case of Leber's hereditary optical atrophy in a family with evident signs of hereditary degenerative neuropathy]. AB - Reference is made to a case of Leber's disease in a patient with other slight neurological signs of the type encountered in hereditary ataxias. The importance of the case lies in the following points: (a) very early onset (this is a rare finding: 2.5% of cases, according to Ronne); (b) the presence of nervous abnormalities of the Charcot-Marie-Tooth amyotrophy type and of hereditary spinal of cerebellar ataxia in some of the 35 members of the patient's family, with or without optical atrophy; (c) the prevalence of the disease, though not to the total exclusion of females, suggesting a primarily diagynic multifactorial form of transmission. The main features of the case are compared with those reported in the literature. PMID- 17340846 TI - [Acute abdomen attributable to cystic lymphangioma of the greater omentum]. AB - A case of acute abdomen in a female child of 15 months caused by a cyst in the great omenturn that was twisted round on its pedicle several times is reported. This is the third case of its kind to be described in Italy and the patient the youngest reported in the world literature. PMID- 17340847 TI - Trends in HIV related risk behaviors. Some good news. PMID- 17340848 TI - Malaria in pregnancy, risk perceptions and care seeking practices among adolescents in Mukono district Uganda. AB - Malaria in pregnancy is a serious health problem that contributes greatly to maternal morbidity and mortality. This study investigated risk perceptions and care seeking practices for malaria in pregnancy among adolescents. Data were collected using focus group disusions(FGDs) and key informant interviews (KIIs). Results showed that malaria was perceived as the leading cause of morbidity and mortality among pregnant women. However, adolescent girls did not consider themselves at risk of malaria even when pregnant. Anaemia and low birth weight were not well understood and not related to malaria in pregnancy. Self-medication was common including over the counter drugs, herbs or a combination of both. When this failed, several options were taken such as seeking care at health units. People preferred to visit heath units with laboratory facilities, since investigations were valued and perceived useful. These investigations were locally known as okukebera omusayi, which translates to examining blood This local term is non-specific and used when patients are referred to laboratories to investigate diseases like HIV, syphilis and malaria. The use of this term however, discourages some people who are afraid of knowing their HIV status. Similarly, the notion that HIV/AIDS is spread thorough contaminated needles and syringes discourages people from giving blood for laboratory tests. In addition, the cost of investigations, fear of pain due to pricking, and the rudeness of laboratory technicians negatively influence seeking laboratory tests. Implications of these findings include developing a health promotion package that explains the dangers of self medication and advocates prompt seeking for malaria treatment especially for adolescents and primigravidae. Policy decisions to introduce rapid diagnostic kits (RDTs) in primary care units including drug shops are required in order to improve effective treatment of malaria. PMID- 17340849 TI - Adolescent risk correlates of bullying and different types of victimization. AB - This study examined correlates of different types of bullying and victimization relevant to the adolescent context. Of particular interest was the importance of risk factors that emerge and/or undergo significant changes during adolescence. Logistic regressions were performed using a representative sample of approximately 6,500 Canadian adolescents. We found that high-levels of victimization (7.6%), bullying (6.1%), and bully-victimization (0.9%) were quite prevalent amongst adolescents. The patterns of risk associated with each of these labels were different from each group. An examination of the different sub-types of victimization revealed that there were differences in both the prevalence and the risk patterns associated with each sub-type. Physical, verbal, and rumor victimization (the most common types) had similar risk patterns, while sexual victimization and ethnic victimization (the least most common type) each had a unique risk pattern. We conclude that emerging and/or changing risk factors associated with adolescent development are significantly related to bullying and victimization, with the specific relationships depending on the specific type of activity examined. These findings suggest that successful intervention strategies should try to be sensitive to the variations in prevalence and relationships with the risk factors. PMID- 17340850 TI - Morbidities associated with bullying behaviors in adolescents. School based study of American adolescents. AB - To assess the prevalence of bullying behaviors and morbidities, including overweight/obesity and frequent physical and emotional symptoms, and the associations between such morbidities and frequent involvement in bullying behaviors among US adolescents in grades 6 through 10. DESIGN, SETTING, AND PARTICIPANTS: This study was based on an analysis of US data from the 1998 World Health Organization Health Behavior in School-aged Children survey. The survey provides nationally representative, cross-sectional survey information on 15,686 US students in grades 6 through 10. OUTCOME MEASURES: Involvement in bullying as a victim and/or as a bully; body mass index; and self-reported headaches, stomachaches, backaches, dizziness, irritability, "feeling low", "feeling nervous", and sleeping difficulties. RESULTS: Fifteen per cent of the students were involved in bullying others and/or were victims of bullies at least once a week. The bullying activities took place both at school and elsewhere. Students who suffered from at least one or more frequent physical or emotional symtom, occuring several times a week, were at 2.4 to 3.5 times more likely to be involved in frequent bullying incidents, as compared to students, who did not experience frequent symptoms. CONCLUSIONS: The present study confirmed that frequent participation in bullying behaviors, as a bully, a victim, or both, was associated with poor health status. The existence of a morbidity spectrum associated with participation in bullying behaviors is important information for pediatric practice and merits further investigation. PMID- 17340851 TI - Disruptive behavioural disorders, self harm and suicidal ideation among German adolescents in psychiatric care. AB - The present study examines the unique and shared risk factors for suicidal behaviour, self-injury, and externally focussed aggressive behaviour among German youths and adolescents of both sexes. Also explored is the issue of multiple maladaptive behaviours and whether or not these are interrelated. The period of the sample comprised 2002-2003 admissions (N = 3694) to a clinic for child and adolescent psychiatry and psychosomatics. Measures were taken from medical psychological documentation ("Ba-Do") and self-report questionnaire and included items relating to self-injurious behaviour, suicidal intent and socially disruptive and threatening behaviour (FAPS). Self and expert ratings of suicidal and self-injurious behaviour were significantly statistically correlated. Overt aggression was unrelated to suicidal behaviour. Suicidal and self-injurious behaviour were more common among female than male adolescents. Age, disharmony within the family and excessive parental demands were major global determinants of suicidal behaviour for both genders, but unrelated to self-injurious or socially disruptive behaviour, the latter being more associated with parental under-involvement and feelings of hostile rejection. Intelligence and age were significant predictors of overt aggression among females; intellectual functioning, number of siblings and disability among family members emerged as major determinants of suicidal behaviour among males. Findings are discussed in terms of practice interventions. PMID- 17340852 TI - Outbreak of measles in medical students and determination of immune status to measles-mumps-rubella viruses. AB - We conducted an investigation after a measles outbreak in medical students to determine the immunity of the medical students, the correlation between history and seropositivity, and measles-mumps-rubella vaccine effectiveness. After a preliminary study done during measles outbreak, a cross-sectional study was planned. Serum samples from 322 medical students were tested by enzyme-linked immunosorbent assay, vaccinated volunteers, then re-tested vaccinees. Histories of measles, mumps and rubella were taken. Of 322 students, seven students (2.2%) were seronegative to measles, 13 (4.0%) to mumps, and 13 (4.0%) to rubella. Historical information revealed 30.4% of sensitivity in measles and 34.3% in mumps, whereas 5.2% in rubella. Among those seronegative on admission and vaccinated, seroconversion rates were 100% (5/5), 90.9% (10/11), 100% (8/8) in measles, mumps and rubella vaccine, respectively. Of 265 vaccinated students parotitis was detected in one female student, arthralgia was observed in three students (1.1%) and myalgia in two (0.7%), and 240 students reported no side effects. We detected the unreliable historical screening and high seroprevalence of measles, mumps and rubella in prevaccine era for mumps and rubella and, safety of MMR vaccination in medical students in Turkey. PMID- 17340853 TI - Relationship between adolescent health behaviors and self-esteem in Turkey. AB - The main objectives of this article were to present first adolescent self-esteem levels including its predictors and second to show the correlations between student self-esteem evaluations, health compromising and risk behaviors. This study was a part of a larger comparative youth research with questionnaires to the students in grade eleven in the Yenimahalle district of Ankara, Turkey. A brief group type questionnaire was administered to the 310 students. The results showed that, the students were not homogeneous in terms of their positive and negative self-esteem levels. Regression analysis revealed that father's educational level as an independent variable was effective on positive self esteem scores. Gender was effective on student negative self-esteem ratings. It was also found that there was a significant correlation between student self esteem evaluations and perceptions about other students along with health compromising and risk behaviors. Prevention implications and recommendations are discussed. PMID- 17340854 TI - Influential sources affecting Bangkok adolescent body image perceptions. AB - The study of body image-related problems in non-Western countries is still very limited. Thus, this study aims to identify the main influential sources and show how they affect the body image perceptions of Bangkok adolescents. The researcher recruited 400 Thai male and female adolescents in Bangkok, attending high school to freshmen level, ranging from 16-19 years, to participate in this study. Survey questionnaires were distributed to every student and follow-up interviews conducted with 40 students. The findings showed that there are eight main influential sources respectively ranked from the most influential to the least influential: magazines, television, peer group, familial, fashion trend, the opposite gender, self-realization and health knowledge. Similar to those studies conducted in Western countries, more than half of the total percentage was the influence of mass media and peer groups. Bangkok adolescents also internalized Western ideal beauty through these mass media channels. Alike studies conducted in the West, there was similarities in the process of how these influential sources affect Bangkok adolescent body image perception, with the exception of familial source. In conclusion, taking the approach of identifying the main influential sources and understanding how they affect adolescent body image perceptions can help prevent adolescents from having unhealthy views and taking risky measures toward their bodies. More studies conducted in non-Western countries are needed in order to build a cultural sensitive program, catered to the body image problems occurring in adolescents within that particular society. PMID- 17340855 TI - The use of illicit substances in adolescent schizophrenia inpatients. AB - Illicit substance use is a common co-morbidity in adolescent-onset schizophrenia/ schizoaffective patients. This study aimed to evaluate the rates of substance use among adolescent schizophrenia inpatients as compared to the general adolescent population. A total of 188 inpatients consecutively admitted to psychiatric adolescent inpatient unit were compared to a representative sample of 26,543 control adolescents screened for substance use by the Israel Anti-Drug Authority during the same time period. All illicit substances, except for opiates, were used in significantly higher rates by the inpatient sample. The distribution of the used psychoactive substances was different in the inpatient setting. Specific prevention and treatment programs must be developed in order to cope with this crucial clinical issue in these high-risk patients. PMID- 17340856 TI - Repetitive eructation (belching) in children: is it pathological? AB - Eructation (belching) is a common symptom encountered in clinical practice. It has a similar mechanism as gastroesophageal reflux disease (GORD), which is transient lower oesophageal relaxation and is generally assumed to be a manifestation of GORD. Repetitive eructation can be distressing and its management can be difficult and challenging. This report highlights this problem in two adolescent children with a comprehensive review and discussion of its etio pathogenesis. PMID- 17340857 TI - Children with intellectual disability in residential care centers. Trends in Israel 1999-2004. AB - Children and adolescents with intellectual disability (ID) have historically gone through various stages from being left or activity killed, to being placed in care, to being rehabilitated or educated and today with efforts to keep as normal a life as possible inspite of their disability. This study was conducted in order to look at the trends of children with ID in residential care centers in Israel. Since 1998 an annual survey of all medical clinics in residentail care centers has been conducted by the Office of the Medical Director of the Ministry of Social Affairs and data was extracted from the national surveys during 1999-2004. Out of a total residential care population of about 6,000 persons with ID about 1,000 were children, but a downward trend was observed over the study period with children 18.1% of the total residential care population in 1999 to 14.4% in 2004 (a total of 954 persons aged 0-19 years in 2004). Further detailed studies should be conducted in order to get a clearer picture of this present pediatric population in residential care. PMID- 17340858 TI - "Comparison of immunochemical (enzyme-linked immunosorbent assay) and immunohistochemical methods for the detection of central nervous system tissue in meat products," a comment on: J. Food Prot. 69(3):644-650 (2006). PMID- 17340859 TI - Transportation and lairage environment effects on prevalence, numbers, and diversity of Escherichia coli O157:H7 on hides and carcasses of beef cattle at processing. AB - Hide has been established as the main source of carcass contamination during cattle processing; therefore, it is crucial to minimize the amount of Escherichia coli O157:H7 on cattle hides before slaughter. Several potential sources of E. coli O157: H7 are encountered during transportation and in the lairage environment at beef-processing facilities that could increase the prevalence and numbers of E. coli O157:H7 on the hides of cattle. On three separate occasions, samples were obtained from cattle at the feedlot and again after cattle were stunned and exsanguinated at the processing plant (286 total animals). The prevalence of E. coli O157:H7 on hides increased from 50.3 to 94.4% between the time cattle were loaded onto tractor-trailers at the feedlot and the time hides were removed in the processing plant. Before transport, nine animals had E. coli O157:H7 in high numbers (> 0.4 CFU/cm2) on their hides. When sampled at the slaughter facility, the number of animals with high hide numbers had increased to 70. Overall, only 29% of the E. coli O157:H7 isolates collected postharvest (221 of 764) matched pulsed-field gel electrophoresis types collected before transport. The results of this study indicate that transport to and lairage at processing plants can lead to increases in the prevalence and degree of E. coli O157:H7 contamination on hides and the number of E. coli O157:H7 pulsed-field gel electrophoresis types associated with the animals. More study is needed to confirm the mechanism by which additional E. coli O157:H7 strains contaminate cattle hides during transport and lairage and to design interventions to prevent this contamination. PMID- 17340860 TI - Effect of Lactobacillus acidophilus strain NP51 on Escherichia coil O157:H7 fecal shedding and finishing performance in beef feedlot cattle. AB - A 2-year study was conducted during the summer months (May to September) to test the effectiveness of feeding Lactobacillus acidophilus strain NP51 on the proportion of cattle shedding Escherichia coli O157:H7 in the feces and evaluate the effect of the treatment on finishing performance. Steers (n = 448) were assigned randomly to pens, and pens of cattle were assigned randomly to NP51 supplementation or no supplementation (control). NP51 products were mixed with water and applied as the feed was mixed daily in treatment-designated trucks at the rate of 10(9) CFU per steer. Fecal samples were collected (n = 3,360) from the rectum from each animal every 3 weeks, and E. coli O157:H7 was isolated by standard procedures, using selective enrichment, immunomagnetic separation, and PCR confirmation. The outcome variable was the recovery of E. coli O157:H7 from feces, and was modeled using logistic regression accounting for year, repeated measures of pens of cattle, and block. No significant differences were detected for gain, intakes, or feed efficiency of control or NP51-fed steers. The probability for cattle to shed E. coli O157:H7 varied significantly between 2002 and 2003 (P = 0.004). In 2002 and 2003, the probability for NP51-treated steers to shed E. coli O157:H7 over the test periods was 13 and 21%, respectively, compared with 21 and 28% among controls. Over the 2 years, NP51-treated steers were 35% less likely to shed E. coli O157: H7 than were steers in untreated pens (odds ratio = 0.58, P = 0.008). This study is consistent with previous reports that feeding NP51 is effective in reducing E. coli O157:H7 fecal shedding in feedlot cattle. PMID- 17340861 TI - Prevalence of class 1 integrons in commensal Escherichia coli from pigs and pig farmers in Thailand. AB - Escherichia coli isolates (n = 617) from fecal samples of healthy and diarrheal pigs, pig farmers, and nonfarmers were analyzed for class 1 integrons. Three hundred ninety-two isolates (63.5%) were positive for class 1 integrons, based on the presence of intI1, with seventy-one of those isolates (11.5%) harboring all three conserved genes (intI1, qacEdelta1, and sul1) known to be associated with class 1 integrons. The presence of integrons was associated with isolate origin. Integrons were more prevalent in isolates from most pig groups than in isolates from pig farmers and nonfarmers. Selected integron-positive and integron-negative isolates were tested for resistance to 16 antimicrobials. All integron-positive swine isolates were multidrug resistant to at least three antimicrobial agents, demonstrating resistance to 14 different antibiotics that included sulphamethoxazole (100%), tetracycline (97.1%), ampicillin (92.8%), streptomycin (89.9%), trimethoprim-sulphamethoxazole (88.1%), nalidixic acid (60.9%), chloramphenicol (58.0%), kanamycin (55.1%), cephalothin (44.9%), gentamicin (39.1%), ciprofloxacin (33.3%), cefoxitin (8.7%), amoxicillin-clavulanic acid (5.8%), and amikacin (2.9%). All isolates were susceptible to ceftiofur and ceftriaxone. Forty-seven resistance patterns were observed among 69 integron positive swine and swine farmer isolates. The most frequent pattern was tetracycline-ciprofloxacin-gentamicin-nalidixic acid-sulphamethoxazole trimethoprim-sulphamethoxazole-kanamycin-ampicillin-streptomycin (10.1%), which was found in diarrheal and healthy pigs. This study shows that integrons and multidrug-resistant commensal bacteria are common and appear to be a significant aspect of microbial communities associated with pigs and humans in southern Thailand. PMID- 17340862 TI - Proteome analysis of virulence factor regulated by autoinducer-2-like activity in Escherichia coli O157:H7. AB - Many pathogenic bacteria, including Escherichia coli O157:H7, can control gene expression in a cell density-dependent manner by producing small signaling molecules (autoinducers) in a process known as quorum sensing. In this study, the effects of the autoinducer-2-like activity on the expression of proteins, including virulence factors, in E. coli O157:H7 were characterized by proteomic analysis. Compared with the control, E. coli O157:H7 strains in the presence of autoinducer-2-like activity exhibited elevated virulence by more rapidly forming cell aggregates on epithelial cells and rapidly killing the nematode Caenorhabditis elegans, the surrogate host. Two-dimensional gel electrophoresis revealed 18 proteins that were upregulated by autoinducer-2-like activity and 4 proteins that were down-regulated. These proteins were further characterized by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry and are involved in the metabolic process, adaptation and protection, cell motility, secretion, envelope biogenesis, and protein translation. These results indicate that the newly identified proteins are associated with the control of virulence in E. coli O157:H7 and that these proteins can be potential targets for the development of antibiotics and other antimicrobial agents. PMID- 17340864 TI - Quantitative analysis of the growth of Salmonella stanley during alfalfa sprouting and evaluation of Enterobacter aerogenes as its surrogate. AB - Raw seed sprouts have been implicated in several food poisoning outbreaks in the last 10 years. Few studies have included investigations of factors influencing the effectiveness of testing spent irrigation water, and in no studies to date has a nonpathogenic surrogate been identified as suitable for large-scale irrigation water testing trials. Alfalfa seeds were inoculated with Salmonella Stanley or its presumptive surrogate (nalidixic acid-resistant Enterobacter aerogenes) at three concentrations (-3, -30, and -300 CFU/g) and were then transferred into either flasks or a bench top-scale sprouting chamber. Microbial concentrations were determined in seeds, sprouts, and irrigation water at various times during a 4-day sprouting process. Data were fit to logistic regression models, and growth rates and maximum concentrations were compared using the generalized linear model procedure of SAS. No significant differences in growth rates were observed among samples taken from flasks or the chamber. Microbial concentrations in irrigation water were not significantly different from concentrations in sprout samples obtaihed at the same time. E. aerogenes concentrations were similar to those of Salmonella Stanley at corresponding time points for all three inoculum concentrations. Growth rates were also constant regardless of inoculum concentration or strain, except that lower inoculum concentrations resulted in lower final concentrations proportional to their initial concentrations. This research demonstrated that a nonpathogenic easy-to isolate surrogate (nalidixic acid-resistant E. aerogenes) provides results similar to those obtained with Salmonella Stanley, supporting the use of this surrogate in future large-scale experiments. PMID- 17340863 TI - Effects of nitrate or nitro supplementation, with or without added chlorate, on Salmonella enterica serovar Typhimurium and Escherichia coli in swine feces. AB - The effects of coincubating the active agent of an experimental chlorate product with nitrate or select nitro compounds, possible inducers and competing substrates for the targeted respiratory nitrate reductase, on concentrations of experimentally inoculated Salmonella enterica serovar Typhimurium and indigenous Escherichia coli were determined. Studies were completed in swine fecal suspensions as a prelude to the administration of these inhibitors to pigs. Results confirmed the bactericidal effect of chlorate (5 to 10 mM) against these fecal enterobacteria, reducing (P < 0.05) concentrations by > 2 log CFU ml(-1) after 3 to 6 h of incubation. An effect (P < 0.05) of pH was observed, with considerable regrowth of Salmonella and E. coli occurring after 24 h of incubation in suspensions buffered to pH 7.1 but not in suspensions buffered to pH 6.5 or 5.6. A 24-h coincubation of fecal suspensions with 5 to 10 mM chlorate and as little as 2.5 mM nitrate or 10 to 20 mM 2-nitro-1-propanol, 2 nitroethanol, and, sometimes, nitroethane decreased (P < 0.05) Salmonella but not necessarily E. coli concentrations. 2-Nitro-1-propanol and 2-nitroethanol exhibited inhibitory activity against Salmonella and E. coli by an undetermined mechanism, even in the absence of added chlorate. PMID- 17340865 TI - Multiple typing for the epidemiological study of the contamination of broilers with Salmonella from the hatchery to the slaughterhouse. AB - Eighteen Belgian broiler flocks were followed from the hatchery to the slaughterhouse by a multiple typing approach (sero-, geno-, and phage types) for the investigation of the transmission of Salmonella and its subtypes. For 12 of the 18 flocks, there was no correlation between the serotypes found preharvest and those isolated from the feces in the transport crates and on the carcasses in the slaughterhouse. Serotypes found in the crates were usually also found on the carcasses. In 5 of the 10 flocks with Salmonella-positive broilers, complex contamination patterns with the involvement of different serotypes, genotypes, or both were revealed. In two of these flocks (flocks 8 and 9), the Salmonella Enteritidis contamination of the broilers could be traced to the hatchery. In flock 9, evidence was found for the acquisition, during rearing, of a megaplasmid in the Salmonella Enteritidis strain. In the other three positive flocks (flocks 6, 7, and 10), the environment and movable material (e.g., footwear) played a determining role in the infection and shedding pattern of the broilers. For flocks 6 and 7, reared consecutively in the same broiler house, a persistent Salmonella Hadar geno/phage type predominated in the preharvest period, while another Salmonella Hadar geno/phage type was found in the house or the environment but never in the broilers. Only for the above-mentioned five flocks were the same strains that were found preharvest also recovered from the carcasses, although these strains were not predominant on the carcasses, with the exception of one flock (flock 10). In conclusion, it can be said that most of the time, Salmonella strains that contaminate Belgian broiler carcasses do not predominate in the preharvest environment. PMID- 17340866 TI - Evaluation of a combined culture and PCR method (NMKL-163A) for detection of presumptive pathogenic Yersinia enterocolitica in pork products. AB - A combined culture and PCR method for detection of pathogenic Yersinia enterocolitica in food (NMKL-163A) was evaluated by testing samples of artificially and naturally contaminated pork. The performance of the pre-PCR sample treatment, buoyant density centrifugation, was first compared with two commercially available methods (DNeasy tissue kit and PrepMan). We found that similar sensitivity was reached (i.e., 25 CFU/g of food was detected by single PCR) with the buoyant density centrifugation and the DNeasy Tissue kit when tested on overnight enrichments. However, the DNeasy tissue kit was superior when tested on nonenriched homogenates; the detection limit was 25 CFU/g in minced beef by single PCR and 25 CFU/g in sausage by nested PCR. We then analyzed 100 raw minced pork samples. Thirty-five tested positive for presumptive pathogenic Y. enterocolitica when analyzed by the NMKL-163A method, whereas none tested positive when analyzed in parallel by a standard culture method (ISO 10273). We also analyzed 97 samples of cold-smoked pork sausage, of which approximately 11% tested positive by the NMKL-163A method. This study showed that sensitivities such as those obtained by nested PCR were required for detection of the pathogen in naturally contaminated samples, and therefore the nested PCR primers, which are included in the NMKL-163A method only as an option, need to be validated and applied routinely. PMID- 17340867 TI - Direct detection and identification of Arcobacter species by multiplex PCR in chicken and wastewater samples from Spain. AB - Twenty-two chicken livers, 10 chicken carcasses, and 15 wastewater samples were processed and analyzed for Arcobacter by PCR and traditional culture methods. Samples were enriched for 24 and 48 h, incubated at 30 degrees C under aerobic conditions, and streaked on blood selective media. To determine the best isolation conditions, 20 samples also were processed under microaerophilic conditions at 37 degrees C. Simple and multiplex PCR assays were used directly with enrichment broths and isolated strains. Seventeen Arcobacter strains were isolated from chicken samples, and A. butzleri was the only Arcobacter species identified. The direct PCR assay revealed that 29 of the 32 chicken samples were contaminated with Arcobacter. A. butzleri was the most frequently detected species, although Arcobacter cryaerophilus also was present in some of the samples and Arcobacter skirrowii occasionally was detected. All the wastewater samples were positive by PCR assay for Arcobacter after 24 h of enrichment. A. butzleri and A. cryaerophilus were detected with the multiplex PCR assay. Fourteen Arcobacter strains were isolated from 10 of the 15 water samples analyzed; 7 were identified as A. butzleri and the remaining 7 were A. cryaerophilus. Both for chicken and water samples, Arcobacter detection rate for PCR amplification was higher than for culture isolation. These results indicate the high prevalence of Arcobacter in chicken and wastewater and the inadequacy of available cultural methods for its detection. The species-specific multiplex PCR assay is a rapid method for assessing Arcobacter contamination in chicken and wastewater samples and is a viable alternative to biochemical identification of isolated strains. PMID- 17340868 TI - Evaluation of a tissue culture-based approach for differentiating between virulent and avirulent Vibrio parahaemolyticus strains based on cytotoxicity. AB - The ability of only a subset of Vibrio parahaemolyticus strains to cause human infection underscores the need for an analytical method that can effectively differentiate between pathogenic strains and those that do not cause disease. We tested the feasibility of a tissue culture-based assay to determine whether clinical isolates could be differentiated from nonclinical isolates based on relative isolate cytopathogenicity. To screen for cytotoxic capability, we measured relative extracellular lactate dehydrogenase as an indicator of host cell damage in five different mammalian cell lines in the presence of V. parahaemolyticus. Isolates originating from clinical sources exhibited 15.5 to 59.3% relative cytotoxicity, whereas those originating from food sources exhibited 4.4 to 54.9% relative cytotoxicity. In the presence of -1.2 x 10(6) cells, cytotoxicity was 1.6- to 3.5-fold higher (P < 0.05) for clinical isolates than for nonclinical isolates in L2, Henle 407, and Caco-2 cell lines. V. parahaemolyticus serotype O3:K6 clinical isolates had 1.6- to 2.1-fold higher cytotoxicity than did the non-O3:K6 clinical isolates, with significantly higher cytotoxicity in HeLa, J774A.1, and Henle 407 cells than in L2 and Caco-2 cells. Because V. parahaemolyticus often is found in oysters, the effect of the presence of an oyster matrix on assay efficacy was also tested with L2 cells. The cytotoxicity elicited by a highly cytotoxic V. parahaemolyticus isolate was not affected by the presence of oyster tissue, suggesting that an oyster matrix will not interfere with assay sensitivity. In the present format, this assay can detect the presence of > 10(5) cells of a virulent V. parahaemolyticus strain in an oyster matrix. PMID- 17340869 TI - Novel Campylobacter isolation method using hydrophobic grid membrane filter and semisolid medium. AB - Culture procedures for isolation of thermophilic campylobacters from food matrices are complex, labor intensive, and time-consuming. Most available methods include the use of antibiotics as selective agents to prevent the growth of competing microflora. A simple procedure for isolation of thermophilic campylobacters after enrichment in Rosef's enrichment broth was developed using a hydrophobic grid membrane filter (HGMF) on semisolid medium (SSM). SSM contains no antibiotics, and the HGMF physically separates Campylobacter from the enrichment broth, allowing isolation based on differential motility. The HGMF-SSM method was compared to the Agriculture and Agri-Food Canada Food Safety Procedures Manual (FSPM-10) method (Isolation of Thermophilic Campylobacters from Fresh Pork, Beef Veal, Poultry and Ready-to-Eat Meat Products), which includes the use of selective antibiotics. During the initial study, after enrichment the HGMF-SSM method yielded pure cultures of campylobacters after 16 to 18 h (overnight) compared with 48 h for the FSPM-10 method. Ninety-four turkey samples collected at local retail stores and 38 frozen pig fecal samples were processed by both methods. Thirty-five samples (26.5%) were positive by the HGMF-SSM method; 24 (18.2%) of these positive samples contained Campylobacter jejuni and 11 (8.3%) contained Campylobacter coli. With the FSPM-10 method, 25 samples (18.9%) were positive: 21 (15.9%) with C. jejuni and 4 (3%) with C. coli. For a subsequent field study, only the HGMF-SSM method was used to isolate Campylobacter from 1,200 chicken samples and 454 turkey samples sold at retail. Analysis of five subisolates from various samples indicated that only one type of Campylobacter was recovered by the HGMF-SSM method, as ascertained by MICs for 10 antimicrobials, sequencing of the short variable region of the flaA gene, and fingerprinting based on amplified fragment length polymorphism. The absence of antibiotics in the SSM may explain the higher recovery of thermophilic campylobacters. The HGMF-SSM method resulted in improved isolation of campylobacters and is simpler, faster, cheaper, and less labor intensive than the FSPM-10 method. The recovery of one type of Campylobacter from the chicken samples may have important implications, particularly in epidemiological studies. PMID- 17340870 TI - Second-order modeling of variability and uncertainty in microbial hazard characterization. AB - This study describes an analytical framework that permits quantitative consideration of variability and uncertainty in microbial hazard characterization. Second-order modeling that used two-dimensional Monte Carlo simulation and stratification into homogeneous population subgroups was applied to integrate uncertainty and variability. Specifically, the bootstrap method was used to simulate sampling error due to the limited sample size in microbial dose response modeling. A data set from human feeding trials with Campylobacter jejuni was fitted to the log-logistic dose-response model, and results from the analysis of FoodNet surveillance data provided further information on variability and uncertainty in Campylobacter susceptibility due to the effect of age. Results of our analyses indicate that uncertainty associated with dose-response modeling has a dominating influence on the analytical outcome. In contrast, inclusion of the age factor has a limited impact. While the advocacy of more closely modeling variability in hazard characterization is warranted, the characterization of key sources of uncertainties and their consistent propagation throughout a microbial risk assessment actually appear of greater importance. PMID- 17340871 TI - Effects of heat-degraded sugars on survival and growth of Vibrio parahaemolyticus and other bacteria. AB - We studied the effects of autoclaved (121 degrees C, 15 min) sugar solutions on the survival and growth of Vibrio parahaemolyticus and other bacteria. The growth and survival of V. parahaemolyticus in Luria-Bertani media and phosphate buffer, respectively, were inhibited by the addition of D-glucose autoclaved in pH 8.0 phosphate buffer. The bactericidal effect of autoclaved D-glucose was very small when autoclaved in pH 7.0 phosphate buffer, but larger effects were observed when autoclaved in the buffer at an alkaline pH. The autoclaving of D-glucose in CH3COONa, NaHCO3, and Na2HPO4 solutions at pH 7.6 to 8.5 also generated bactericidal effects, but it was not the case when D-glucose was autoclaved in Na2SO4, (NH4)2SO4, or NH4Cl solution at pH 8.0. The same effects as autoclaved D glucose were observed in autoclaved lactose, D-fructose, and D-ribose. The bactericidal effects of autoclaved D-glucose were also noted in Salmonella Enteritidis, Listeria monocytogenes, and E. coli strains, but the effects were smaller than those seen in V. parahaemolyticus and V. vulnificus. The growth of V. parahaemolyticus in clam extracts was also inhibited by the addition of autoclaved D-glucose, indicating that heat-treated reduced sugars can exert bactericidal effects in foods. PMID- 17340873 TI - Effect of inhibitory liquid smoke fractions on Listeria monocytogenes during long term storage of frankfurters. AB - Listeria monocytogenes is a potential health hazard that sometimes finds harborage in facilities that manufacture ready-to-eat meats, including frankfurters. Our objectives were to examine the effect of select liquid smoke extracts on control of L. monocytogenes on frankfurters. Frankfurters were either obtained locally at retail (containing lactate-diacetate) or manufactured for us in-house or by a local processor (without added lactate-diacetate). In challenge studies of retail franks containing lactate-diacetate, low levels of L. monocytogenes were able to increase by 2 to 8 log on 5 of 10 brands tested when held at 1.6 degrees C (35 degrees F). Treatments with liquid smoke extracts were able to reduce and control growth of L. monocytogenes on the most permissive franks for 10 weeks when treated for as long as 90 s to as little as 5 s versus untreated controls. Effective control of L. monocytogenes was also obtained when dipped for as short as 1 s or when dropped through an atomized mist produced by a pressurized spray canister. Frankfurters manufactured without lactate-diacetate by a large commercial manufacturer of franks were sprayed with liquid smoke by using a commercial device as they exited the peeler. When inoculated at three different levels (10(1), 10(2), and 10(3) CFU) with a four-strain cocktail of L. monocytogenes and stored at 6 degrees C (43 degrees F), the smoke-treated samples again demonstrated effective control of L. monocytogenes relative to untreated control samples. Frankfurters produced in-house without lactate-diacetate and treated while still in the casing also showed suppression of Listeria compared with controls. The data show that surface application of liquid smoke extracts by dipping or spraying may inhibit the growth of L. monocytogenes on frankfurters during shelf life and should facilitate a claim as an alternative 2, and possibly alternative 1, process for (U.S. Food and Drug Administration) hazard analysis and critical control point purposes. PMID- 17340872 TI - Fate of Listeria monocytogenes in commercial ham, formulated with or without antimicrobials, under conditions simulating contamination in the processing or retail environment and during home storage. AB - Commercial cured ham formulated with or without potassium lactate and sodium diacetate was inoculated with Listeria monocytogenes and stored to simulate conditions of processing, retail, and home storage. The ham was sliced, inoculated with a 10-strain composite of L. monocytogenes (1 to 2 log CFU/cm2), vacuum packaged, and stored at 4 degrees C to simulate contamination following lethality treatment at processing (first shelf life). After 10, 20, 35, and 60 days of storage, packages were opened, samples were tested, and bags with remaining slices were reclosed with rubber bands. At the same times, portions of original product (stored at 4 degrees C in original processing bags) were sliced, inoculated, and packaged in delicatessen bags to simulate contamination during slicing at retail (second shelf life). Aerobic storage of both sets of packages at 7 degrees C for 12 days was used to reflect domestic storage conditions (home storage). L. monocytogenes populations were lower (P < 0.05) during storage in ham formulated with lactate-diacetate than in product without antimicrobials under both contamination scenarios. Inoculation of ham without lactate-diacetate allowed prolific growth of L. monocytogenes in vacuum packages during the first shelf life and was the worst case contamination scenario with respect to pathogen numbers encountered during home storage. Under the second shelf life contamination scenario, mean growth rates of the organism during home storage ranged from 0.32 to 0.45 and from 0.18 to 0.25 log CFU/cm2/day for ham without and with lactate-diacetate, respectively, and significant increases in pathogen numbers (P < 0.05) were generally observed after 4 and 8 days of storage, respectively. Regardless of contamination scenario, 12-day home storage of product without lactate-diacetate resulted in similar pathogen populations (6.0 to 6.9 log CFU/cm2) (P > 0.05). In ham containing lactate-diacetate, similar counts were found during the home storage experiment under both contamination scenarios, and only in 60-day-old product did samples from the first shelf life have higher (P < 0.05) pathogen numbers than those found in samples from the second shelf life. These results should be useful in risk assessments and for the establishment of "sell by" and "consume by" date labels for refrigerated ready-to eat meat products. PMID- 17340874 TI - Use of octanoic acid as a postlethality treatment to reduce Listeria monocytogenes on ready-to-eat meat and poultry products. AB - The antilisterial efficacy and organoleptic impact of an octanoic acid (OA)-based treatment for ready-to-eat (RTE) meat and poultry products were investigated. Whole-muscle and comminuted RTE products were inoculated with a five-strain mixture of Listeria monocytogenes. The OA treatments were applied to the surface of RTE products by dispensing a specific volume of solution directly into the final package prior to vacuum sealing. Once sealed, the vacuum-packaged RTE products containing OA were immersed in water heated to 93.3 degrees C (200 degrees F) for 2 s to effect adequate film shrinkage. Extending the time at which the packaged, treated RTE products were exposed to water heated to 93.3 degrees C was also evaluated with a commercial cascading shrink tunnel fitted with a modified drip pan. Once treated, RTE products were examined for survivor populations of L. monocytogenes after 24 h of storage at 5 degrees C. Sensory evaluation was conducted with a 60-member trained panel on 11 uninoculated, treated RTE products. The OA treatment of RTE products reduced L. monocytogenes numbers to between 0.85 log CFU per sample (oil-browned turkey) and 2.89 log CFU per sample (cured ham) when compared with controls. The antilisterial activity of OA was improved by increasing the duration of the heat shrink exposure. Specifically, reductions of L. monocytogenes ranged from 1.46 log CFU per sample (oil-browned turkey) to 3.34 log CFU per sample (cured ham). Results from the sensory evaluation demonstrated that 10 of the 11 treated RTE products were not perceived as different (P < or = 0.05) from the untreated controls. Panelists detected reduced (P < or = 0.05) smoke flavor intensity with treated mesquite turkey, although the treated product was viewed as acceptable. Results demonstrate the effectiveness of OA as a postlethality treatment meeting U.S. Food Safety and Inspection Service regulatory guidelines for RTE meat and poultry products with minimal impact on sensory quality. PMID- 17340875 TI - Influence of salt, smoke, and high pressure on growth of Listeria monocytogenes and spoilage microflora in cold-smoked dolphinfish (Coryphaena hippurus). AB - The effects of different salting and smoking conditions on the growth of Listeria monocytogenes in cold-smoked dolphinfish (Coryphaena hippurus) fillets were evaluated. High concentrations of phenol (72.47 ppm) and salt (3.25%) in muscle inhibited L. monocytogenes growth in smoked fish stored at 20 degrees C for 4 days. The antibacterial effect of high pressure in cold-smoked dolphinfish during long-term chilled (5 degrees C) storage was evaluated in fillets prepared according to two different sets of salting and smoking conditions. Combining the milder salting and smoking conditions (1.97% salt and 42 ppm phenol) with a high pressure treatment of 300 MPa at 20 degrees C for 15 min sufficed to exert a bacteriostatic effect on the total viable bacteria, total lactic acid bacteria, and L. monocytogenes. However, in fillets prepared using the more severe salting and smoking conditions (2.93% salt and 82 ppm phenol), pressurization kept L. monocytogenes counts under the detection limit throughout 100 days of storage. A similar effect was obtained by dosing the fillets with nisin. No luminescent bacteria, hydrogen sulfide-producing bacteria, or Enterobacteriaceae were found in any of the fillets produced using either of the two sets of processing conditions. PMID- 17340876 TI - Treatment of vegetable sauces with enterocin AS-48 alone or in combination with phenolic compounds to inhibit proliferation of Staphylococcus aureus. AB - The antimicrobial activity of enterocin AS-48 against Staphylococcus aureus was tested in vegetable sauces, alone and in combination with phenolic compounds. When added alone at 25 microg/ml, AS-48 inactivated all detectable staphylococci in napoletana and pesto sauces stored at 22 degrees C, but it only caused limited growth inhibition when these sauces were stored at 10 degrees C, as well as in other sauces such as carbonara and green sauce for fish. At 80 microg/ml, AS-48 eliminated all detectable staphylococci in napoletana, pesto, and green sauce for fish regardless of storage temperature, but it still had much more limited effect in carbonara sauce. Antistaphylococcal activity was potentiated significantly when AS-48 was used in combination with the phenolic compounds carvacrol, geraniol, eugenol, terpineol, caffeic acid, p-coumaric acid, citral, and hydrocinnamic acid. The efficacy of the combined treatments depended both on the phenolic compound and the type of sauce. In carbonara sauce stored at 22 degrees C, the combinations of 80 microg/ml AS-48 and 20 mM hydrocinnamic acid or 126 mM carvacrol reduced viable counts of staphylococci below detection limits for up to 30 days. PMID- 17340877 TI - Antibiotic susceptibility profiles of Lactobacillus reuteri and Lactobacillus fermentum. AB - Lactobacillus reuteri and Lactobacillus fermentum, which are commonly used as food processing aids and probiotics, can potentially act as reservoirs of antibiotic resistance genes. Acquired resistance genes may be transferred via the food chain or in the gastrointestinal tract to pathogenic bacteria. Knowledge of the distributions of antibiotic MICs for a species is needed when using a phenotypic method to assess the presence of acquired resistance genes. In the present study, 56 L. reuteri and 56 L. fermentum strains that differed by source and spatial and temporal origin were assessed for antibiotic susceptibility using an Etest kit and a broth microdilution protocol. L. fermentum strains displayed a uniform distribution of MICs for all six antibiotics tested. L. reuteri strains had a bimodal distribution of MICs or a distribution with MICs above the test range for 7 of the 14 antibiotics tested. Genetic relatedness was observed among L. reuteri strains with high MICs for both ampicillin and tetracycline and among strains with high MICs for both erythromycin and clindamycin. Results obtained with the Etest and the broth microdilution method corresponded well with each other. Thus, further research may make it possible to define microbiological breakpoints for distinguishing between strains with and without acquired resistance genes. PMID- 17340878 TI - Use of the gfp gene in monitoring bacteriocin-producing Lactobacillus plantarum N014, a potential starter culture in nham fermentation. AB - Lactobacillus plantarum N014 is a bacteriocin-producing lactic acid bacteria originally isolated from nham, a traditional Thai fermented sausage, and in the process of development to be used as a starter culture for nham fermentation. During the fermentation process, there is a need to identify the starter culture among several naturally occurring bacteria. In this study, a new plasmid carrying the gfp (green fluorescent protein) gene was constructed based on pGKV210, an Escherichia coli/ Lactococcus shuttle vector containing an erythromycin resistance marker. The gfp gene derived from pGFPuv was placed under the control of an L-lactate dehydrogenase promoter and then inserted at the EcoRI site of pGKV210, leading to pN014-GFP. The novel plasmid was used to transform L. plantarum N014, which is a bacteriocin-producing lactic acid bacteria isolated from nham. The resulting transformant, L. plantarum N014-GFP+, was brightly fluorescent and harbored the expected plasmid. A plasmid stability test revealed that pN014-GFP was stable after 100 generations of growth under nonselective pressure. L. plantarum N014-GFP+ and its parent strain were shown to be very similar in growth rate, bacteriocin production, and lactate production. L. plantarum N014-GFP+ was able to survive in a nham model. The survival clones were still fluorescent and harbored pN014-GFP. PMID- 17340879 TI - Evaluating in vitro antimicrobial activity of thymol toward hygiene-indicating and pathogenic bacteria. AB - Results of a study of the kinetics of bacterial inhibition by thymol in order to develop appropriate applications for the compound in food systems are presented. A modeling-based approach was used to provide a quantitative description of the antimicrobial activity of thymol toward some foodborne pathogens and hygiene indicating bacteria, which could be postprocessing contaminants of ready-to-eat meat products. The effect of the active compound on the bacterial growth was assessed from growth kinetics curves and dose-response profiles in a wide range of thymol concentrations, i.e., from 50 to 1,000 ppm. Inhibitory data were produced using a macrodilution methodology based on a turbidimetric technique. Microbial response was discussed in terms of Gompertz's parameters as well as in terms of the active concentration of thymol affecting the growth status of microbial suspension (noninhibitory concentration and MIC). Results suggested that thymol can be successfully used as an alternative antimicrobial to increase the lag time as well as to decrease the maximum value of the growth index as reached in the stationary phase of the growth cycle for all investigated bacteria. Due to their high sensitivity to the antimicrobial stress as observed at sub-MIC, it is arguably a potential use of thymol for assurance of food safety and hygiene in combination with other preservative technologies. A quantitative evaluation of the antimicrobial properties of the active compound was performed using a macrodilution methodology based on a turbidimetric technique to produce inhibitory data. Both the growth kinetics and inhibition profile in a wide range of thymol concentrations were obtained for each test bacterium, mathematically modeled, and analyzed. Noninhibitory concentration and MIC were determined to investigate both the microbial sensibility and resistance toward thymol, and Gompertz's parameters were evaluated to assess the microbial response at each phase of growth cycle. The in vitro-obtained results suggested that thymol may be successfully used as a alternative preservative to increase the lag time as well as to decrease the maximum cell load reached in the stationary phase of growth cycle for all investigated bacteria. PMID- 17340880 TI - Assessing the hygiene of pig carcasses using whole-body carcass swabs compared with the four-site method in EC Decision 471. AB - An investigation was carried out in a pig abattoir to determine the microbiological status of carcasses being produced after slaughter and dressing. The carcasses were sampled in accordance with EC Decision 471 in relation to the application of hazard analysis critical control point (HACCP) criteria to the slaughter of animals. In this regard, four sites on the animals were examined on five consecutive carcasses during each of 10 visits for the presence of total viable counts and Enterobacteriaceae. A comparison of the EC four-site method, with a whole-body swab technique, as a means of measuring carcass contamination found that the two methods gave significantly different results for both groups of organisms. A comparison of the mean of the individual data from the four sites with the data from the pooled samples revealed that there was a poor relationship between the two. Samples may be taken by excision or swabbing and allocated to three categories of process control, which, in turn, are based on microbiological criteria that are different, depending on whether sampling is by excision or swabbing. The influence of these changes in microbiological criteria is discussed in relation to the categorization of samples as acceptable, marginal, or unacceptable and the influence this has on process control. Finally, the proposed introduction of Salmonella as a safety indicator in the EC HACCP system is discussed. PMID- 17340881 TI - Microbiological characterization of imported and domestic boneless beef trim used for ground beef. AB - The United States imports lean boneless beef trim from Australia (AUS), New Zealand (NZL), and Uruguay (URY) to meet demand for ground beef production. The reported incidence of and etiological agents responsible for foodborne diseases differ between these countries and the United States. Our objective was to determine whether current U.S. microbiological profiling adequately addresses the potential differences between foreign and domestic beef trim. We compared the hygienic status of imported and domestic (USA) beef trim by enumeration of aerobic bacteria, Enterobacteriaceae, coliforms, Escherichia coli, and Staphylococcus aureus. We also compared the prevalence of pathogens between imported and domestic samples by screening for the presence of Salmonella, Campylobacter spp., Listeria spp., and non-O157 Shiga toxin-producing E. coli (STEC). A total of 1,186 samples (487 USA, 220 AUS, 223 NZL, and 256 URY) of boneless beef trim were analyzed. Results of enumeration revealed significant differences between samples from all countries, with the lowest pathogen numbers in samples from AUS and the highest in samples from URY. Six Salmonella isolates (1 NZL, 1 URY, and 4 USA), 79 L. monocytogenes isolates (4 AUS, 5 NZL, 53 URY, and 17 USA), and 7 Campylobacter isolates (1 NZL, 1 URY, 5 USA) were found among the trim samples tested. Non-O157 STEC prevalence was 10% in NZL samples and about 30% in all of the other samples; 99 STEC strains were isolated. Serotyping of these isolates revealed that serotypes associated with hemolytic uremic syndrome were not different in prevalence between imported and domestic beef trim. Although it may be tempting to do so, these data cannot be used to compare the microbiological quality of beef trim between the countries examined. However, these results indicate that the current pathogen monitoring procedures in the United States are adequate for evaluation of imported beef trim. PMID- 17340882 TI - Enterococci from Appenzeller and Schabziger raw milk cheese: antibiotic resistance, virulence factors, and persistence of particular strains in the products. AB - Enterococci are natural residents of human and animal intestinal tracts, and grow to high numbers in a variety of cheeses. The aim of this study was to determine the diversity of enterococci in two types of artisanal raw milk cheese (Schabziger and Appenzeller) and to investigate whether particular strains with triple resistance against chloramphenicol (Chl), tetracycline (Tet), and erythromycin (Ery) persist in the production system. Of 46 cheese samples, a total of 312 Enterococcus strains were isolated over a 5-month period on selective agar plates containing Chl, Tet, or, Ery. Enterococcus faecalis was the predominant species (80.7%), followed by Enterococcus faecium (5.1%), and Enterococcus durans (11.7%). According to the phenotypic resistance patterns, a selection of 150 strains was analyzed with PCR for the presence of genes encoding resistance to Ery (ereA, ereB, mphA, ermA, ermB, ermC, mrsA/mrsB, mefA/mefE), and Tet (tetM, tetL). Because virulence factors have been linked to the pathogenicity of enterococci, the strain selection was also tested for the presence of the following virulence factors: Agg, GelE, Cyl, Esp, EfaAfs, EfaAfm, Cpd, Cob, and Ccf. All tested strains contained at least two of the nine virulence genes taken into analysis. Pulsed-field gel electrophoresis patterns of the isolates showed a limited persistence of several strains over a period of 1 to 2 months in Schabziger, and more than 2 months in Appenzeller. Finally, the enterococcal flora in the two types of cheeses seems to be rather unrelated. Within 150 strains from 25 different cheese samples (11 Appenzeller and 14 Schabziger), 41 pulsed-field gel electrophoresis patterns could be identified, and only 1 of these was found in enterococci from both types of cheese. PMID- 17340883 TI - Use of logistic regression with dummy variables for modeling the growth-no growth limits of Saccharomyces cerevisiae IGAL01 as a function of sodium chloride, acid type, and potassium sorbate concentration according to growth media. AB - A global logistic model was used to study the effects of both quantitative variables (NaCl, acid, and potassium sorbate concentrations) and dummy variables (laboratory medium or brine, and citric, lactic, or acetic acids) on growth of Saccharomyces cerevisiae IGAL01. The deduced equations, with the significant coefficients selected by a backward stepwise procedure, allowed estimations of the simultaneous comparison of behaviors of levels of the qualitative variables as a function of the quantitative variables and the development of the growth-no growth limits according to laboratory medium or brine and the different types of acidifying agents. The S. cerevisiae growth region in yeast malt glucose peptone broth was always wider than that in brine, in which this yeast was inhibited by 0.03% potassium sorbate and 6% NaCl, when the acid concentration (regardless of type) was 0.2 to 0.3%. These results demonstrate the applicability of such model designs to include qualitative variables in investigations related to the development of growth-no growth limits. PMID- 17340884 TI - Effect of processing and storage conditions on the generation of acrylamide in precooked breaded chicken products. AB - The generation of acrylamide was determined during frying and cold storage of breaded chicken products. The role of the batter crust on acrylamide formation also was evaluated. The effect of storage under a modified atmosphere on the fate of acrylamide was investigated during a 23-day storage period under refrigeration. Acrylamide was analyzed by using normal phase high-performance liquid chromatography according to a previously developed methodology that allows for dual identity verification as acrylamide and acrylic acid and determination of concentrations as low as 10 microg liter(-1), which corresponds to 20 microg kg(-1) of solid sample. For the total 28 commercial precooked samples analyzed, initial acrylamide concentrations ranged between 0.91 and 0.97 mg kg(-1) and were attributed to the combined effect of batter and meat. In all cases, acrylamide concentrations increased during storage, attaining a maximum (1.36 to 1.80 mg kg( 1)) between day 15 and day 19. The maximum value was observed in samples packaged under air, and the minimum value was observed under a modified atmosphere mixture of 60% CO2-40% N2. In this group, the maximum acrylamide concentration was reached after 19 days of storage. These data indicate that there is a high concentration of acrylamide in precooked, battered protein foods and that the concentration changes considerably during storage, which may lead to almost twice the initial amounts when air is present within the package. PMID- 17340885 TI - Evidence for internalization of Escherichia coli into the aerial parts of maize via the root system. AB - Escherichia coli introduced into the hydroponic growing medium of maize plants was detected 48 h later in the shoot. Decapitation of root tips or severing of the plant root system at the root-shoot junction enhanced bacterial internalization. The density of the bacteria in shoots of plants with damaged roots or removed root systems was 27.8 and 23.9 times higher than that in plants with intact roots, respectively. The concentration of viable cells in the hydroponic solution decreased over time from 9.3 x 10(6) CFU/ml at the time of inoculation to 8.5 x 10(1) CFU/ml 4 days thereafter. The number of E. coli cells associated with the roots also decreased with time, but a significant decline appeared only at 4 days postinoculation. At the time of sampling for E. coli presence in the shoot, 10(2) CFU/ml was present in the nutrient solution and 8 x 10(3) CFU/g was associated with the roots. The present study is the first to demonstrate internalization of E. coli via the root in a monocotyledonous plant. PMID- 17340886 TI - A longitudinal study of Salmonella shedding and antimicrobial resistance patterns in North Dakota feedlot cattle. AB - Salmonella is one of the most frequent causes of foodborne illness worldwide, and transmission involves foods of animal origin such as beef. The objective of this study was to monitor the prevalence of Salmonella fecal shedding in feedlot cattle during the finishing period and to assess the antimicrobial resistance patterns of the isolated salmonellae. On arrival at the feedlot, 1 (0.7%) of the 144 steers was shedding Salmonella in its feces. After 28 days on feed, shedding was detected in 8 (5.6%) of the 144 steers. At the third sampling, 19 (13%) of 143 steers were shedding, and the number of shedders continued to increase to 89 (62%) of 143 at the last sampling. Salmonella shedding was significantly influenced (P < 0.0001) by sampling time but not by herd of origin. All Salmonella isolates identified belonged to serotype Typhimurium serovar Copenhagen, a type commonly isolated from Salmonella infections in humans. Antimicrobial resistance testing of the isolates revealed five multidrug resistance patterns, two of which accounted for 104 (95.4%) of 109 of the isolates. All the isolates were susceptible to ceftiofur, and all were resistant to spectinomycin, sulfathiazole, tiamulin, florfenicol, ampicillin, penicillin, chlortetracycline, oxytetracycline, and clindamycin. Data from this study indicate that a high prevalence of antimicrobial-resistant Salmonella strains can sometimes be found in feedlot cattle in North Dakota. These data will contribute to risk assessment of Salmonella shedding by cattle in feedlots and highlight the need to continue preharvest monitoring for this organism. PMID- 17340887 TI - Listeria monocytogenes F2365 carries several authentic mutations potentially leading to truncated gene products, including inlB, and demonstrates atypical phenotypic characteristics. AB - Searches of the genome annotation of Listeria monocytogenes F2365, an isolate from the 1985 listeriosis epidemic in California, showed that this strain carries 20 authentic mutations resulting in premature stop codons, including a nonsense mutation in inlB. Here we showed that L. monocytogenes F2365 demonstrates atypical virulence-associated characteristics, including significantly (P < 0.05) reduced invasion efficiency in Caco-2 cells as compared with a closely related lineage I serotype 4b strain as well as significantly (P < 0.05) greater variation in invasiveness when grown under different conditions compared with standard laboratory control and other lineage I serotype 4b strains. In addition, L. monocytogenes F2365 demonstrated distinct growth characteristics, including a significantly (P < 0.05) reduced exponential growth rate when compared with laboratory control and other lineage I serotype 4b outbreak-associated strains as well as a significantly (P < 0.05) longer lag phase duration time compared with another lineage I serotype 4b strain. Our results support that L. monocytogenes F2365 is characterized by genotypic and phenotypic properties that are atypical of other L. monocytogenes strains. PMID- 17340888 TI - Foodborne outbreak caused by Staphylococcus aureus: phenotypic and genotypic characterization of strains of food and human sources. AB - An outbreak of staphylococcal food poisoning involving approximately 180 people occurred in Brodowski, Sao Paulo State, Brazil, in April 1998. Strains of Staphylococcus aureus isolated from foods and food handlers, implicated as the etiologic agent, were characterized with phenotypic (phage typing, antibiotic susceptibility test, and enterotoxin production), and genotypic (random amplified polymorphic DNA) characterization. Strains isolated from vegetable salad with mayonnaise sauce, broiled chicken, pasta in tomato sauce, and from the oropharyngeal secretions of five food handlers--A, B, C, H, and I--showed the same phage profile and antibiotic resistance. Random amplified polymorphic DNA generated 17 combined profiles with primers OPE-20 and OPA-7. The similarity of strains was analyzed by generating a dendrogram that classified the 59 strains of S. aureus into four major clusters (I, II, III, and IV). Strains from four food handlers (A, B, H, and I) and from vegetable salad with mayonnaise, broiled chicken, and pasta in tomato sauce showing the same phage type profile and resistance to antibiotics belonged to the same cluster and produced staphylococcal enterotoxin A. Therefore, these foods and food handlers were incriminated in the outbreak. PMID- 17340889 TI - Temporal occurrence of Cryptosporidium in the Manila clam Ruditapes philippinarum in northern Adriatic Italian lagoons. AB - In order to evaluate the temporal occurrence of Cryptosporidium oocysts in Ruditapes philippinarum clams bred along the northeastern Italian Adriatic coast and molecularly characterize the isolates, 2,160 specimens (180 clams per month) were collected from three clam farms from January to December 2004. Two farms (sites A and B) were located in Venice (Chioggia, Veneto region) and one (site C) in the Marano Lagoons (Friuli Venezia Giulia region). Clams from 36 pools (i.e., one pool of 60 clams per month per site) were subjected to a high-sensitivity seminested PCR assay specific for a 360-bp diagnostic region internal to the Cryptosporidium spp. outer wall protein gene. Positive amplicons were sequenced and analyzed. Cryptosporidium DNA was found in clams from seven pools (sites A and B) during 1 month of sampling at site A and 6 months of sampling at site B, with Cryptosporidium hominis and Cryptosporidium parvum being detected. The expected infection rate of the clams was 0.36%. Site B showed a significantly higher expected infection rate (1.15%) than did the other sites (A = 0.14% and C = 0%). Given its high sensitivity and specificity, this seminested PCR assay can be considered a reliable tool for detecting and distinguishing species within the Cryptosporidium genus. The seasonal pattern of contamination and the related public health risks are of particular concern. PMID- 17340890 TI - Survival of calicivirus in foods and on surfaces: experiments with feline calicivirus as a surrogate for norovirus. AB - Although there is a large body of evidence incriminating foods as vehicles in the transmission of norovirus, little is known about virus survival in foods and on surfaces. Feline calicivirus was used as a surrogate for norovirus to investigate its survival in representative foods of plant and animal origin and on metal surfaces. Known concentrations of feline calicivirus in a natural fecal suspension were deposited onto lettuce, strawberries, ham, or stainless steel and incubated for 7 days at refrigeration or room temperatures. Virus was recovered at 1-day intervals, and the titers of the virus were determined by plaque assay. Infectious virus was recoverable until day 7 from lettuce, ham, and stainless steel. Statistically higher titers of feline calicivirus (P < 0.05) were recovered from ham under all conditions than from lettuce, strawberries, or stainless steel. These data provide valuable information for epidemiological and monitoring purposes as well as for the development of food processing practices and appropriate strategies to inactivate norovirus and control its transmission via foods and surfaces. PMID- 17340891 TI - An efficient and rapid method for recovery of norovirus from food associated with outbreaks of gastroenteritis. AB - Noroviruses have emerged as the most common cause of foodborne outbreaks of acute nonbacterial gastroenteritis. In this study, two methods for the extraction of viruses from deli ham were compared. Using both methods, as little as 1 to 10 reverse transcription (RT)-PCR units of inoculated norovirus and enterovirus could be detected by nested RT-PCR assays. The fastest and most efficient extraction method based on TRIzol LS Reagent was chosen to identify viruses in food items associated with three different outbreaks. Norovirus was detected using nested (real time) RT-PCR assays that target the genome region routinely used for diagnosis of human cases, thereby facilitating the comparison of sequences detected in food and clinical specimens. For one outbreak, a norovirus sequence (163/163 nucleotides) identical to those detected in clinical samples was found on salami sliced by a food handler with a recent history of gastroenteritis. For the other two outbreaks, norovirus was detected on leftovers of spareribs and ham, but fecal samples from affected persons were not available. The methods used in this study may be useful in future outbreak investigations because the extraction method is easy to perform and suitable for this particular type of food and the detection method facilitates direct comparison of patient and food data. PMID- 17340892 TI - Vomitoxin and zearalenone content of soft wheat flour milled by different methods. AB - Given the prominence and the growing importance of mycotoxins in human and animal health, and particularly of vomitoxin and zearalenone in people who use wheat and wheat products as their staple diet, we investigated two different types of wheat milling. Wheat produced according to good manufacturing practice related to mycotoxin risks (from sowing to harvesting) was used to compare the vomitoxin and zearalenone content of soft wheat flour, following the use of two different types of milling, traditional milling with a stone mill and modern milling with a roller mill. Moreover, the vomitoxin and zearalenone content was also evaluated in commercial stone-milled and roller-milled flours. Our results show that stone milling reduced vomitoxin and zearalenone content in flours, compared with the use of the roller-mill system. PMID- 17340893 TI - Presence and significance of Bacillus cereus in dehydrated potato products. AB - Dehydrated potato contains Bacillus cereus at a prevalences of 10 to 40% and at numbers usually less than 10(3) CFU g(-1). B. cereus in dehydrated potato is likely to be present as spores that are able to survive drying of the raw vegetable and may represent a significant inoculum in the reconstituted (rehydrated) product where conditions favor germination of, and outgrowth from, spores. Holding rehydrated mashed potato alone, or as part of another product (e.g., potato-topped pie), at temperatures above 10 degrees C and below 60 degrees C may allow growth of vegetative B. cereus. Levels exceeding 10(4) CFU g( 1) are considered hazardous to human health and may be reached within a few hours if stored inappropriately between these temperatures. Foods incorporating mashed potato prepared from dehydrated potato flakes have been implicated in B. cereus foodborne illness. This review is a summary of the information available concerning the prevalence and numbers of B. cereus in dehydrated potato flakes and the rate at which growth might occur in the rehydrated product. PMID- 17340894 TI - Science in the land of google. PMID- 17340895 TI - Immediate loading of dental implants supporting fixed partial dentures in the posterior mandible: a randomized controlled split-mouth study--machined versus titanium oxide implant surface. AB - PURPOSE: A split-mouth study was conducted to compare dental implants with either machined or titanium oxide (TiO) surfaces immediately loaded with fixed partial dentures in the posterior mandible. MATERIALS AND METHODS: Ten patients with bilateral partial edentulism in the posterior mandible received 42 implants; 20 on the test (TiO) and 22 on the control (machined) side. The implants were loaded within 24 hours postsurgery. At implant placement the maximum insertion torque (IT) was recorded. Implant stability quotient (ISQ) was also evaluated at baseline (day 0) and 1, 2, 4, 12, 24, and 52 weeks following implant placement. The radiographic bone level (RBL) change was measured on periapical radiographs at baseline and 12 months after loading. Means for the 2 groups were compared by paired t test. RESULTS: The overall implant success rate was 95%. No implants were lost in the test group; 2 failed in the control group. The difference between the groups in RBL change after 1 year of function was not statistically significant (P = .224). However, average RBL change for machined implants in distal positions was significantly higher than for TiO surface implants in the same position (post-hoc comparison; P = .048). ISQ and peak IT values did not differ between the groups (P = .414 and P = .762, respectively). The high IT necessary to insert the implants did not seem to affect the RBL change (P = .203). CONCLUSIONS: No significant difference was observed between machined and TiO implant surface in terms of RBL change or ISQ, although TiO implants may provide a lower RBL change compared to machined implants when utilized in the distal position. Immediate loading of implants using fixed partial dentures in posterior mandible may be considered as a treatment option if implants are inserted with IT > or = 20 Ncm and ISQ > or = 60 into nonaugmented bone and loaded with light centric occlusal contact. PMID- 17340896 TI - Bone defect formation during implant placement following alveolar distraction. AB - PURPOSE: This retrospective study was designed to evaluate the volume of hard tissue generated at the time of implant placement in distracted alveolar bone. MATERIALS AND METHODS: All patients who underwent distraction osteogenesis between 2000 and 2003 were included. The preoperative bone height, amount of distraction performed, and presence or absence of complications affecting implant placement were recorded. The augmentation achieved was correlated with insufficient bone formation using the Spearman correlation and the Fisher exact test. RESULTS: The study included 43 implants placed in 17 cases of alveolar distraction. Of the 34 implants placed in bone augmented by 4.5 to 6.5 mm, bone defects were observed with 12. All 9 implants placed in ridges augmented by 7 to 10.5 mm demonstrated a bone defect. The "defect" and "no-defect" implant groups differed significantly with respect to preoperative bone height and amount of distraction performed (P < .001 for both). Significantly more defects were formed in bone augmented by > 25% compared to bone augmented by < 25% (P < .001). CONCLUSIONS: When considering distraction osteogenesis, augmentation of up to 25% of the initial bone height seems more predictable and less likely to be associated with complications at the time of implant placement. In distractions greater than 25% of the original height, additional treatment should be considered. PMID- 17340897 TI - The effect of delayed versus early loading on nitric oxide metabolism around dental implants: an 18-month comparative follow-up study. AB - PURPOSE: Nitrite is a stable end-product of nitric oxide oxidation. The aim of the present study was to quantitatively analyze peri-implant sulcular fluid (PISF) nitrite levels in a longitudinal study design to evaluate the potential changes in nitric oxide metabolism in relation to the clinical status of the peri implant site and the loading style of the dental implants. MATERIALS AND METHODS: A total of 34 implants, either early loaded (EL) or delayed loaded (DL), in 17 patients were followed up for a period of 18 months. Clinical parameters were recorded, PISF samples were obtained, and PISF nitrite levels were spectrophotometrically determined. Clinical measurements and nitrite analysis were repeated at 1, 3, 6, 9, 12, and 18 months. RESULTS: Despite the gradual decrease in clinical parameters, fluctuations in PISF total nitrite levels were observed during follow-up. The pattern of nitric oxide metabolism, as reflected by PISF nitrite levels, also demonstrated differences between EL and DL implants that diminished toward the end of the experimental period. DISCUSSION: Although the presence of clinical and subclinical gingival inflammation contributes to the PISF total nitrite levels, nitric oxide metabolism is also associated with healing and bone remodeling, and the pattern of loading seemed to have an impact on nitric oxide production at dental implant sites. CONCLUSION: Nitric oxide production at dental implant sites seems to be tightly regulated to enable the maintenance of peri-implant bone. PMID- 17340898 TI - The effect of bone condensation and crestal preparation on the bone response to implants designed for immediate loading: a histomorphometric study in dogs. AB - PURPOSE: The aim of this study was to evaluate the influence of bone condensation and crestal preparation on the bone response of implants designed to promote osseocompression. MATERIALS AND METHODS: In the first phase, the mandibular premolars of 6 dogs were extracted bilaterally. After 8 weeks, each dog received 8 Xive implants (4 per hemimandible). One hemimandible was randomly assigned to the experimental group and the other to the control group. The implant site was prepared using conventional standard drills. Prior to implant placement the crestal drill was used in the experimental group but not in the control group. After 12 weeks, the animals were sedated and sacrificed. The hemimandibles were removed and prepared for histomorphometric analysis of bone-implant contact (BIC) and bone density of areas adjacent to and further from the implant surface. RESULTS: The mean +/- SD percentages of BIC attained were 71.1% +/- 11.8% and 45.1% +/- 16.1% for the experimental and control groups, respectively. The bone density analysis revealed that in the control group, percentage BIC was a mean of 55.6% +/- 11.3% adjacent to the implant and 50.7% +/- 17.9% distant from the implant. In the experimental group, percentage BIC was a mean of 71.1% +/- 8.6% adjacent to the implant and 55.6 +/- 11.3 distant from the implant. The difference between the experimental and control groups was statistically significant for both parameters, BIC and bone density, in the adjacent areas (P < .0001). CONCLUSION: Crestal preparation is of fundamental importance for this implant system, since it led to better bone response, represented by the improved BIC and bone density. PMID- 17340899 TI - Use of a surgical navigation system for CT-guided template production. AB - PURPOSE: The purpose of this study was to evaluate in vitro the accuracy of 2 methods for computerized tomography (CT)-guided template production via a surgical navigation system. MATERIALS AND METHODS: Oral implants were planned on CT scans of standard dental stone casts with integrated target pellets. Method 1 used the aiming device of the navigation system for direct positioning of 2-mm surgical bur tubes on the dental stone casts. In method 2, the aiming device was used to guide drillings into the dental stone casts, and the surgical bur tubes were indirectly positioned by metal rods inserted in the drill holes. In both methods the bur tubes were affixed in a resin template. The accuracy of the obtained templates was evaluated by postoperative CT scans using descriptive statistics and the Student t test (P < .05 considered significant). RESULTS: The mean accuracy (normal deviation from the defined targets) of method 1 was 0.5 +/- 0.3 mm (max 1.2 mm; n = 56). Mean accuracy for method 2 was 0.6 +/- 0.3 mm (max 1.4 mm; n = 56). No significant difference was found between the maxillary and mandibular templates. DISCUSSION: Conventional navigation systems already installed in many hospitals may be used for surgical template production. In contrast to intraoperative tool tracking, there is no need for patient tracking, and the planned implant axis can be rigidly secured as precisely as technically feasible with the help of an aiming device. CONCLUSION: Both methods of bur tube positioning may represent a precise means for CT-guided template production. PMID- 17340900 TI - Conventional versus CO2 laser-assisted treatment of peri-implant defects with the concomitant use of pure-phase beta-tricalcium phosphate: a 5-year clinical report. AB - PURPOSE: Recently, histologic studies in the beagle dog model demonstrated that CO2 laser-assisted implant decontamination can result in reosseointegration. Consequently, the purpose of this study was to assess the efficacy of CO2 laser assisted therapy as compared with conventional therapy, with the concomitant use of beta-tricalcium phosphate, in humans. MATERIALS AND METHODS: The study included 32 patients with 73 ailing implants. In the laser group, 22 implants were treated with soft tissue resection following laser decontamination; whereas in 17 implants, bone augmentation was performed. In the control group, soft tissue resection after conventional decontamination was performed in 19 implants, augmentation in 15 implants. Results were evaluated 4 months after surgery and in May 2004. RESULTS: Four months after therapy, there were no significant differences in distance from implant shoulder to the first bone contact (ie, DIB values) between implants undergoing laser decontamination and soft tissue resection and implants treated with conventional decontamination followed by soft tissue resection. At the end of the study, there was a statistically significant difference between these 2 groups. Four months after therapy, DIB values after laser decontamination and augmentation were significantly more favorable than after conventional decontamination and augmentation. This difference was no longer detectable at the end of the study. CONCLUSION: Based on the results of this study, it may be concluded that the treatment of peri-implantitis may be accelerated by using a CO2 laser concomitant with soft tissue resection. However, with respect to long-term results in augmented defects, there seems to be no difference between laser and conventional decontamination. PMID- 17340901 TI - Immediate functional loading of implants placed with flapless surgery in the edentulous maxilla: 1-year follow-up of a single cohort study. AB - PURPOSE: To evaluate success rates and complications of implants placed with a flapless technique and immediately loaded in fully edentulous maxillae. MATERIALS AND METHODS: Implants were placed in fully edentulous maxillae with a minimum insertion torque of 45 Ncm in underprepared sites to allow maximum stability at insertion using a flapless technique. Implants were immediately loaded. Outcome measures were prosthesis and implant success, biologic and prosthetic complications, pain, and edema evaluation. Stability of individual implants was assessed both manually and with Osstell at baseline and after 12 months of loading. A single sample t test was used with a significance level of .05. RESULTS: Thirty-three consecutively treated edentulous patients received 202 implants in the maxilla. In 10 patients, 53 implants were immediately inserted in fresh extraction sockets. At implant insertion, a flap had to be elevated to control the direction of the drill in 5 patients. Three implants in 2 patients did not reach sufficient stability and were left to heal for 45 to 90 days. All restorations (21 fixed prostheses and 12 overdentures) were delivered the same day of the surgery. Twenty-six patients experienced no or slight postoperative pain; 7 experienced moderate to severe pain. No or slight edema was recorded for 19 patients and moderate to severe edema for 14 patients. Two implants failed in 2 patients but were successfully replaced the same day they were removed. No major complications occurred. Five patients experienced biologic complications, eg, peri-implantitis; 10 experienced prosthetic complications. No prosthesis failed; however, 1 patient was unsatisfied with his overdenture and requested a fixed alternative. There was a highly significant difference (P < .001) between the stability at implant insertion and after 12 months. CONCLUSION: Implants placed in the edentulous maxilla with a flapless procedure can be successfully loaded the same day of surgery. PMID- 17340902 TI - Comparison of radiographic bone height assessments in panoramic and intraoral radiographs of implant patients. AB - PURPOSE: To compare the ability of 2 radiographic methods, intraoral and panoramic radiography, commonly used in private practices following implant treatment to provide reliable information about the level of peri-implant marginal bone. An additional aim was to compare the inter- and intraobserver reliability. MATERIALS AND METHODS: Patients with implants placed in the mandible in 10 private practices were studied retrospectively. Postoperative intraoral and panoramic radiographs were evaluated at a university oral radiology clinic. Two observers, a specialist in oral and maxillofacial radiology and a specialist in oral and maxillofacial surgery, assessed the bone level, and the thread at which the marginal bone seemed to be attached was registered for the distal and mesial surfaces of all implants at 2 assessments several weeks apart. Kappa statistics was used to compare the agreement between assessments, observers, and methods of radiography. RESULTS: Intraobserver agreement was good or very good, while interobserver agreement was predominantly moderate. The agreement rate between the methods was also moderate. Seven percent of the sites were not possible to assess, with a small difference in favor for panoramic radiographs. In the assessment of the panoramic radiographs, the radiologist found more sites too difficult to assess than the surgeon did. CONCLUSIONS: In this study, panoramic radiographs were found to be as reliable as conventional intraoral radiographs when used to assess the point of bone attachment to implant threads. Intra- and interobserver agreement were reliable but not excellent. The radiologist was more successful in finding sites where the bone level was impossible to assess accurately. PMID- 17340903 TI - Bone strains around immediately loaded implants supporting mandibular overdentures in human cadavers. AB - PURPOSE: To compare the biomechanical effect of splinted versus unsplinted mandibular implants supporting overdentures subjected to experimental static immediate load on bone tissue deformation using strain gauge analysis. MATERIALS AND METHODS: Strain gauges were bonded on the labial cortical bone adjacent to 2 Straumann dental implants placed in the mandibular interforaminal region of 4 completely edentulous mandibles of fresh human cadavers. The installation torque value (ITV) of each implant was measured using a custom-made torque wrench, and implant stability quotients (ISQs) were also obtained using resonance frequency analysis. Three overdentures (ODs), 2 splinted (bar- and cantilevered bar retained) and 1 unsplinted (ball-retained), were fabricated for each edentulous mandible. Two experimental loads were applied subsequently via 2 miniature load cells that were placed bilaterally 10 mm (anterior loading) and 15 mm (posterior loading) from the implant. Strain measurements were performed at a sample rate of 10 KHz and under a maximum experimental static load of 100 N; they were simultaneously monitored from a computer connected to a data acquisition system. Finally, the removal torque values (RTV) of the implants were measured. RESULTS: Strains on the labial cortical bone around implants supporting mandibular ODs under anterior loading were significantly higher than measured under posterior loading for all attachment types (P < .05). All strain values were compressive in nature, and the minimum strain (-19 microepsilon) was recorded for bar-retained ODs under 25 N posterior loading, while the maximum strain (-797 microepsilon) was for recorded for retentive anchor-retained ODs under 100 N anterior loading. Nonparametric correlations between ISQs, ITVs, and RTVs identified significant correlations only for ITVs and RTVs (P < .05). CONCLUSION: Splinting of 2 interforaminal dental implants, regardless of attachment type, to support mandibular ODs subjected to immediate load significantly reduced initial bone tissue strains experienced on the labial cortical bone in comparison with the use of unsplinted implants. PMID- 17340904 TI - A meta-analysis of clinical studies to estimate the 4.5-year survival rate of implants placed with the osteotome technique. AB - PURPOSE: To estimate the survival rate of implants placed with the osteotome technique by means of a systematic review. MATERIALS AND METHODS: The literature was searched using Medline; the search was limited to the years 1953 to 2005. Inclusion criteria were: (1) clinical studies or clinical reports investigating the osteotome technique for dental implantation and (2) control or test group(s) from clinical studies or clinical reports, even if they did not fit with other criteria. By pooling the data of the included studies, overall Kaplan-Meier survival curves were constructed for the periods before and after loading. RESULTS: The initial literature search yielded 164 studies. After selection criteria were applied, 5 studies were considered suitable for inclusion. The combined data of 349 implants revealed survival probabilities of 98% (confidence interval [CI], 97.2% to 100%) until loading and 99% (CI, 94% to 100%) after 56 months of loading. At the end of the observation period 41 implants in 18 patients were still at risk. CONCLUSION: The outcome of dental implantation using the osteotome technique in terms of implant survival seems to be similar to that of implants placed by means of the conventional implantation technique. PMID- 17340905 TI - Factors affecting late implant bone loss: a retrospective analysis. AB - PURPOSE: Prevention of late implant bone loss is a critical component in long term success of implants. The aim of the present study was to evaluate factors affecting late implant bone loss. MATERIALS AND METHODS: Three hundred thirty nine endosseous root-form dental implants placed between April 1981 and April 2002 in 69 patients were analyzed. The implants were categorized based on the following factors: (1) surface characteristics (smooth versus rough), (2) length (short [< 10 mm] versus long [> or = 10 mm]), width (narrow [< 3.75 mm], regular [3.75 to 4.0 mm], or wide [> 4.0 mm]), (3) the amount of keratinized mucosa (< or > or = 2 mm), (4) location (anterior versus posterior; maxilla versus mandible), (5) type of prosthesis (fixed versus removable), and (6) type of opposing dentition. The effects of these factors on clinical parameters, especially average annual bone loss (ABL), were evaluated clinically and radiographically by a blinded examiner. The parameters evaluated were modified Plaque Index, Gingival Index, modified Bleeding Index, probing depth, and ABL. RESULTS: Shorter implants, wider implants, implants supporting fixed prostheses, and implants in smokers were found to be associated with greater ABL (P < .05). The random intercept mixed effects model showed that implant length was the most critical factor for maintenance of ABL. CONCLUSIONS: Shorter implants, wider implants, implants supporting fixed prostheses, and implants in smokers were associated with greater ABL. Implant length was the most significant factor in the maintenance of dental implants. Randomized controlled clinical trials are needed to confirm the results obtained from this retrospective clinical study. PMID- 17340906 TI - Lingual perimandibular vessels associated with life-threatening bleeding: an anatomic study. AB - PURPOSE: To describe the anatomy of the lingual perimandibular vessels and emphasize the distance to the bone. MATERIALS AND METHODS: The hemifacial lower third was dissected in 12 human cadavers. The blood vessels in the floor of the mouth were exposed using sagittal incisions at the canine, mental foramen, and second molar areas. RESULTS: The diameter of the dissected vessels ranged from 0.5 to 3 mm (mean, 1.5 mm). Most vessels were found superior to the mylohyoid muscle in the canine area and beneath the muscle in the mental and second molar areas. The smallest median vertical distance from blood vessel to bone was in the canine area (14.5 mm), followed by the mental foramen area (15.5 mm) and the second premolar area (19 mm). The median horizontal distance of the vessels from the lingual plate was 2 mm at the canine and second molar areas and 4 mm at the mental area. DISCUSSION: Lingual plate perforation, especially anterior to the canine area, can easily injure blood vessels in the floor of the mouth and cause life-threatening hemorrhage following implant placement. Bleeding can occur when the mandibular lingual plate is perforated. Care should be taken to recognize situations where this complication may occur. CONCLUSIONS: Based on the study of human cadavers, it appears that vessels in the floor of the mouth are sometimes in close proximity to the site of implant placement. Caution should be exercised when placing implants in this area. PMID- 17340907 TI - Computer-assisted design of orbital implants. AB - PURPOSE: The purpose of this study is to report on the use of a computer-assisted design (CAD) system for predictable preoperative planning of orbital implant surgery (determination of the optimal number and position of orbital implants). MATERIALS AND METHODS: Preoperative computed tomographic data were processed by interactive software for predictable surgical planning of orbital implant placement. Reformatted images from axial scans were used to analyze the structure of orbital bone and to plan the number of implants to place and the sites in which to place them. RESULTS: Surgeries to correct orbital defects in 6 patients were successfully designed with this method. Seventeen implants were placed in 6 patients with the CAD system with no intraoperative injuries. Satisfactory anatomic and esthetic results were achieved. CONCLUSIONS: The new CAD system optimized preoperative surgical planning for orbital implant placement. The software may be applied in other craniofacial areas for implant placement in the future. PMID- 17340909 TI - Osteonecrosis in the jaws of patients who are using oral biphosphonates to treat osteoporosis. PMID- 17340908 TI - A novel drilling procedure and subsequent bone autograft preparation: a technical note. AB - PURPOSE: To describe a new drilling system that allows the surgeon to obtain autologous living bone that, when associated with a plasma rich in growth factors (PRGF), can be used in bone grafting. MATERIALS AND METHODS: Bone particles collected using both conventional and new drilling systems were analyzed by means of optic and electronic microscopy in 10 patients. Blood was collected from 43 volunteers and used to prepare PRGF. Quantitative aspects of the PRGF, including number of platelets and concentration of growth factors (insulin growth factor [IGF-I], transforming growth factor [TGF-beta1], platelet-derived growth factor [PDGF-AB], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF], and epidermal growth factor [EGF]) were assessed. A demonstrative case study was presented. RESULTS: Microscopic examination showed that the bone structure and the presence of living cells in the bone chips were conserved in all samples obtained from drilling at low speed, whereas material obtained by conventional drilling did not maintain these qualities. Mean counts for TGF-beta1 (55.27 +/- 16.23 ng/mL), PDGF-AB (27.96 +/- 12.13 ng/mL), VEGF (421.09 +/- 399.0 pg/mL), EGF (455.49 +/- 210.04 pg/mL), and HGF (605.70 +/- 269.20 pg/mL) were significantly correlated with the number of platelets (590,000 +/- 197,000 platelets/microL; P < .05). DISCUSSION AND CONCLUSION: The new drilling procedure was developed based on biologic criteria. The method may reduce damage to the host tissue and can be used to obtain a mass of living bone for subsequent grafting in association with autologous growth factors. This new procedure may present new possibilities for enhanced bone healing and needs to be evaluated in a clinical trial. PMID- 17340910 TI - Safety evaluation of certain contaminants in food. Prepared by the Sixty-fourth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). PMID- 17340911 TI - Fine line, big difference. Are you skeptical or cynical? PMID- 17340912 TI - Tune in to the event horizon. Sometimes, you can see danger coming.... PMID- 17340913 TI - On-scene decon. In a chemical incident with multiple casualties, where should you take them all? PMID- 17340914 TI - EMTALA warning. Hospitals told: no "parking"patients with EMS crews. PMID- 17340915 TI - As good as advertised: mobile hospital shines in Katrina response. PMID- 17340916 TI - Emergency management a growing field. PMID- 17340917 TI - Sharing the wealth: LLIS lets responders learn from each other. PMID- 17340918 TI - Get 'em out alive: evacuation considerations for EMS. PMID- 17340919 TI - Planning for the utilization of air medical resources for large-scale incidents. PMID- 17340920 TI - Real-time pediatric disaster response system taking shape. PMID- 17340921 TI - EMS and medical surveillance. PMID- 17340922 TI - Beyond the basics: five pitfalls in medical incident management. PMID- 17340923 TI - Hazardous-materials recognition. PMID- 17340924 TI - A service-driven approach. Interview by John Erich. PMID- 17340925 TI - Are you ready to respond? PMID- 17340926 TI - Prehospital pharmacology: nitrous oxide. AB - Nitrous oxide is a potent inhalational anesthetic/analgesic that is safe and effective for out-of-hospital use. It is a regulated drug that must be purchased and prescribed by a physician. Thus, its use will be limited to those EMS systems where it is allowed by local, regional or state formulary and approved by the system medical director. PMID- 17340927 TI - Coping with violent people: a multi-part series. PMID- 17340928 TI - Surviving the night shift. PMID- 17340929 TI - Leadership tips. Loving EMSers: the key to leading EMTs. PMID- 17340930 TI - Education pitfalls. The value of realistic classroom training. PMID- 17340931 TI - Taking it with you. Creating the presentation that plays anywhere. PMID- 17340932 TI - Five steps to scene safety. PMID- 17340933 TI - Forensic nursing: a healthcare response to the epidemic of violence. PMID- 17340934 TI - Turn to nurses for health care reform solutions. PMID- 17340935 TI - Improving pediatric immunization rates in a safety-net delivery system. Denver Health wins 2006 JCAHO Codman Quality Award. PMID- 17340936 TI - Reference and attitude in infant pointing. AB - We investigated two main components of infant declarative pointing, reference and attitude, in two experiments with a total of 106 preverbal infants at 1;0. When an experimenter (E) responded to the declarative pointing of these infants by attending to an incorrect referent (with positive attitude), infants repeated pointing within trials to redirect E's attention, showing an understanding of E's reference and active message repair. In contrast, when E identified infants' referent correctly but displayed a disinterested attitude, infants did not repeat pointing within trials and pointed overall in fewer trials, showing an understanding of E's unenthusiastic attitude about the referent. When E attended to infants' intended referent AND shared interest in it, infants were most satisfied, showing no message repair within trials and pointing overall in more trials. These results suggest that by twelve months of age infant declarative pointing is a full communicative act aimed at sharing with others both attention to a referent and a specific attitude about that referent. PMID- 17340937 TI - Referential communication abilities and Theory of Mind development in preschool children. AB - This work aims to analyse the specific contribution of social abilities (here considered as the capacity for attributing knowledge to others) in a particular communicative context. 74 normally developing children (aged 3;4 to 5;9, M = 4.6) were given two Theory of Mind (ToM) tasks, which are considered to assess increasing complexity levels of epistemic state attribution: Attribution of knowledge-ignorance (Pillow, 1989; adapted by Welch-Ross, 1997) and Understanding of False-belief (Baron Cohen, Leslie & Frith, 1985). Subjects were paired according to their age and level of performance in ToM tasks. These dyads participated in a referential communication task specially designed for this research. The resulting communicative interchanges were analysed using a three level category system (pragmatic functions, descriptive accuracy, and ambiguity of messages). The results showed significant differences among subjects with different levels of social comprehension regarding the type of communicative resources used by them in every category level. In particular, understanding of false belief seems to be the most powerful predictor of changes in the children's development of communicative competence. PMID- 17340938 TI - Reduction in syllable onsets in the acquisition of Polish: deletion, coalescence, metathesis and gemination. AB - This paper focuses on four strategies of onset reduction employed by a single child (4;0-4;4) acquiring Polish: deletion, coalescence, metathesis, and gemination. Deletion and coalescence occur in word-initial onsets while metathesis and gemination are restricted to word-medial position. The data, which constitute an intriguing 'conspiracy' case (Kisseberth, 1970), are analysed within OPTIMALITY THEORY (henceforth, OT; Prince & Smolensky, 1993/2004; McCarthy & Prince, 1995) in which all surface-true 'processes' are motivated through the interaction of ranked and violable constraints. The OT account makes it possible to envisage the four strategies as different surface responses to the undominated *COMPLEXOnset which militates against onset clusters. The choice of a particular strategy as well as its restriction to a particular word position is not random but follows from the interplay between *COMPLEXOnset, sonority-based syllable structure constraints (Margin Hierarchy, CONTACT LAW), context-sensitive markedness constraints (CODA CONDITION, *Nasal-Fricative) and faithfulness constraints. The present study confirms previous sonority-based findings, supplies further evidence for universal sonority mechanisms from word-medial clusters, and points to the coexistence of child-specific and abstract adult based phonological strategies in the child's system. PMID- 17340939 TI - Understanding the developmental dynamics of subject omission: the role of processing limitations in learning. AB - P. Bloom's (1990) data on subject omission are often taken as strong support for the view that child language can be explained in terms of full competence coupled with processing limitations in production. This paper examines whether processing limitations in learning may provide a more parsimonious explanation of the data without the need to assume full competence. We extended P. Bloom's study by using a larger sample (12 children) and measuring subject omission phenomena in three developmental phases. The results revealed a Verb Phrase-length effect consistent with that reported by P. Bloom. However, contrary to the predictions of the processing limitations account, the proportion of overt subjects that were pronominal increased with developmental phase. The data were simulated with MOSAIC, a computational model that learns to produce progressively longer utterances as a function of training. MOSAIC was able to capture all of the effects reported by P. Bloom through a resource-limited distributional analysis of child-directed speech. Since MOSAIC does not have any built-in linguistic knowledge, these results show that the phenomena identified by P. Bloom do not constitute evidence for underlying competence on the part of the child. They also underline the need to develop more empirically grounded models of the way that processing limitations in learning might influence the language acquisition process. PMID- 17340940 TI - Crosslinguistic evidence for the diminutive advantage: gender agreement in Russian and Serbian children. AB - Our previous research showed that Russian children commit fewer gender-agreement errors with diminutive nouns than with their simplex counterparts. Experiment 1 replicates this finding with Russian children (N = 24, mean 3;7, range 2;10-4;6). Gender agreement was recorded from adjective usage as children described animal pictures given just their names, varying in derivational status (diminutive/ simplex), novelty, and gender. Experiment 2 extends the gender-agreement elicitation methodology developed for Russian to Serbian, a language with similar morphosyntactic structure but considerably fewer diminutives in child-directed speech. Serbian children (N = 22, mean age 3;8, range 3;0-4;1), exhibited an advantage for diminutive nouns of almost the same magnitude as the Russian children. The fact that the diminutive advantage was found in a language with a low frequency of diminutives in the input suggests that morphophonological homogeneity of word clusters and membership in dense neighbourhoods are important factors that contribute to the reduction of inflectional errors during language development. PMID- 17340941 TI - The information in third-person /s/: acquisition across dialects of American English. AB - The production of third-person /s/ on English verbs seems to be ahead of comprehension. Mainstream American English (MAE) is contrasted with African American English (AAE), in which /s/ is rarely supplied. Two studies explored what information children get solely from /s/ on the end of a verb. Sixty-five MAE- and 65 AAE-speaking four- to seven-year-olds participated in one of two experimental picture-choice comprehension studies. Neither group of four-year olds could use the /s/ to determine if the event was generic rather than past tense on a verb (e.g. cuts/cut), or whether it was a verb or a noun compound as in The penguin dresses/The penguin dress. MAE-speakers do not use the information in third-person /s/ alone until age five, and not reliably until age six years. In keeping with AAE production, AAE-speaking children do not use the information in /s/ at all in this age range. PMID- 17340943 TI - Three is not always a crowd: contexts of joint attention and language. AB - This study examined 32 children's (M age = 1;8 years) engagement in joint attention (JA) and the relation between JA and vocabulary size across mother child (MC) and mother-child-sibling (MCS) contexts. In the MCS context, mothers engaged in JA more with one child than both children; they engaged in less JA with target child than they did in the MC context. JA style was generally unrelated across the contexts. Coordinated JA and children's vocabulary were significantly related only for the MCS context. Findings suggest the number of social partners influences JA dynamics and multi-child contexts can be positive language learning environments. PMID- 17340942 TI - Bilingual children's repairs of breakdowns in communication. AB - This study examined two- (n = 10) and three-year-old (n = 16) French-English bilingual children's repairs of breakdowns in communication that occurred when they did not use the same language as their interlocutor (Language breakdowns) and for other reasons (e.g. inaudible utterance). The children played with an experimenter who used only one language (English or French) during the play session. Each time a child used the other language, the experimenter made up to five requests for clarification, from non-specific (What?) to specific (Can you say that in French/English?). The experimenter also made requests for clarification when breakdowns occurred for other reasons, e.g. the child spoke too softly, produced an ambiguous utterance, etc. Both the two- and three-year olds were capable of repairing Language breakdowns by switching languages to match that of their experimenter and they avoided this repair strategy when attempting to repair Other breakdowns. Moreover, they switched languages in response to non-specific requests. The results indicate that even two-and-a-half year-old bilingual children are capable of identifying their language choice as a cause of communication breakdowns and that they can differentiate Language from Other kinds of communication breakdowns. PMID- 17340944 TI - Self-disclosure in psychotherapy supervisors: gender differences. AB - OBJECTIVE: This article will explore the possible reasons for gender differences found in self-disclosure in psychotherapy supervisors. METHOD: Trainees and supervisors in the Brown University Department of Psychiatry and Human Behavior completed a questionnaire that asked about the appropriateness of the actions of a psychotherapy supervisor. RESULTS: On three items, male and female supervisors differed significantly in their perceptions of appropriate boundaries. These items were: interacting with the resident alone outside of supervision e.g. playing tennis (p = .0005), publishing identifiable content of supervision discussions with resident's consent (p = .0006), and disclosing the supervisor's prior struggles with substance abuse (p = .0008). Female supervisors answered "never" to these items in greater numbers than the male supervisors, who, for the most part answered "occasionally". CONCLUSION: Traditional gender role behaviors and differential gender socialization patterns are possible reasons for the gender difference in perception of boundaries by supervisors. PMID- 17340945 TI - Trauma-focused, present-centered, emotional self-regulation approach to integrated treatment for posttraumatic stress and addiction: trauma adaptive recovery group education and therapy (TARGET). AB - We describe the rationale and procedures for a trauma-focused, present-centered, emotion self-regulation modelfor concurrent treatment of posttraumatic stress disorder (PTSD) and substance use disorders: Trauma Adaptive Recovery Group Education and Therapy (TARGET). Based on a review of the clinical and research literatures relevant to models of psychotherapy for co-occurring PTSD and addiction, we develop a conceptual model and describe a skill set that has been operationalized in TARGET. Clinical vignettes with challenging cases are provided to illustrate the application of the TARGET model in individual and group psychotherapy of co-occurring PTSD and addiction. PMID- 17340946 TI - Ego development and the therapeutic goal-setting capacities of mentally ill adults. AB - What capacity do chronically mentally ill adults have for envisioning personal development as evidenced by the ability to set therapeutic goals? This study explored how individual differences in ego development (Loevinger, 1976) predict the therapeutic goal-setting capacities of adults with chronic mental illness receiving therapy in a community mental health setting. The sample included 51 men and 49 women, ages 25 to 65, diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. Utilizing correlational and multiple regression analyses, results confirmed a relationship between higher stages of ego development and greater complexity of therapeutic goals, as well as greater commitment to therapeutic goals. Rehabilitation goals were more prevalent at lower stages of ego development, while goals such as enhancing one's personal relationships, and gaining increased insight emerged at higher stages. Implications for therapeutic change are discussed. PMID- 17340947 TI - Making sense of client data: clinical experience and confirmationism revisited. AB - The purpose of this study was to examine if the order in which case file material is presented to clinicians and length of clinical experience affect clinical judgment. Using think-aloud procedures, 36 clinicians (trainees and veterans) diagnosed the case files of a middle-aged hospital outpatient. In one version, a neutral but vivid datum was placed near the start; in the second version it was placed toward the end. Protocols generated were coded on the dependent variables, confirmation and disconfirmation of earlier inferences, and dispositional and situational inferences. MANOVA results indicate that there is an interactive order-by-experience effect on proportion of confirmatory inferences articulated by participants. Other analyses indicate that order of information presentation but not level of practitioner experience is related to the variance in the proportion of contextual and dispositional inferences articulated by participants. Implications for praxis and for training programs are examined. PMID- 17340948 TI - Predictive validity of patient and therapist attachment and introject styles. AB - This study assessed introject and attachment styles of patients and therapists, and the match of these styles in patient/therapist dyads, to determine their relation to various psychotherapy process and outcome measures. The INTREX was used to measure introject style (affiliation and autonomy) and the Relationship Scale Questionaire to measure attachment style (secure, fearful, preoccupied, dismissing). Therapists with more affiliative (self-loving) and secure styles achieve better outcome results compared to therapists with less affiliative (self hating) and insecure styles. Further, the greater the difference in introject and attachment styles within the patient/therapist dyad, the better the outcome. PMID- 17340950 TI - Search narrows for gene tied to prostate cancer in African-Americans. PMID- 17340951 TI - Is it time to dump a payer? PMID- 17340952 TI - Taking the pressure out of pressure ulcer therapy. PMID- 17340953 TI - Door-to-balloon time: the race is on. PMID- 17340954 TI - Bone marrow aspiration and biopsy. PMID- 17340955 TI - Matters of the heart. PMID- 17340956 TI - Manic for medication safety. PMID- 17340957 TI - Speak, and ye shall be heard. PMID- 17340958 TI - Paving the way for the second wave of EHR adoption. PMID- 17340959 TI - Picking up the pace. PMID- 17340960 TI - One part tech, two parts process. PMID- 17340962 TI - Disaster-proof patients. PMID- 17340961 TI - It's not easy being lean, but scripting can help. PMID- 17340963 TI - Hospitals: get ready for severity-adjusted reimbursement. PMID- 17340964 TI - Take heart: RCM strategies enhance financial health. PMID- 17340965 TI - A clinician-centric medical results viewer. AB - webAzyxxi has become an integral part of medical practice at MedStar Health. As a modern, component, object-based, three-tier Web-application, webAzyxxi 2.0 is capable of rapid expansion through the introduction of both enterprisewide and per hospital functionality. As it is 100 percent client platform agnostic, webAzyxxi is capable of suppporting both today's operating systems and tomorrow's healthcare divices with embedded Web browsers. PMID- 17340966 TI - Less paper, less fuss, better patient care. PMID- 17340967 TI - Reliable mobile computing. PMID- 17340968 TI - Time for the patient safety movement to coalesce for greater effectiveness. PMID- 17340969 TI - [Results of the residential cardiac rehabilitation in patients after myocardial infarction treated with percutaneous coronary intervention (PCI)]. AB - Patients after cardiac infarct and primary PCI are mainly people shortly immobilized with slight damage of the heart muscle with good condition and low consciousness of the disease. Development of the cardiology gives new goals for a cardiac rehabilitation. Traditional rehabilitation targets just like preventation results of immobilization and raising of efficiency are now not so important. Main task of modern rehabilitation, except function improvement of life quality, is preventation of progress coronary disease and reduction of mortality by changing health behavior, especially consent to regular physical activity. The purpose of this study was to evaluate physical efficiency and life quality of life in patients after myocardial infarction treated with PCI who participated in residential cardiac rehabilitations according to age and time of beginning this process. 167 patients (male) after myocardial infarction treated with primary PCI in age 33-82 years, mean age 57,1 +/- 8,92 (years). All patients participated in a 20 +/- 2 (days) comprehensive residential cardiac rehabilitation. ECG treadmill exercise test according Bruce protocol was performed after beginning and at the end of rehabilitation process. Quality of life was evaluated according to SF-36 questionnaire completed at the beginning and after rehabilitation programm. Residential cardiac rehabilitation increases physical efficiency and improves quality of life in patients who undergo primary PCI after myocardial infarction. Effects of cardiac rehabilitation dose not depend on age or on time of beginning of rehabilitation. Most significant increase of physical efficiency was observed in patients who were referend to cardiac rehabilitation no longer then 6 weeks after cardiac event. PMID- 17340970 TI - [N-terminal pro-brain natriuretic peptide (NT-proBNP) and ischemia modified albumin (IMA) in exercise induced ischemia in patients with stable coronary artery disease]. AB - INTRODUCTION: Preliminary data indicate that B type natriuretic peptides' levels may rise in exercise induced myocardial ischemia in patients with stable coronary artery disease. Such findings hint at a potential broader application of these markers reaching beyond its present use in chronic heart failure and acute coronary syndromes. Ischemia modified albumin (IMA) is a novel diagnostic marker in acute coronary syndromes as its value increases in states of myocardial ischemia and necrosis. The role of this marker in the assessment of exercise induced myocardial ischemia in stable coronary artery disease has not been extensively investigated and remains unknown. AIM: To examine changes in N terminal pro-brain natriuretic peptide (NT-proBNP) and ischemia modified albumin (IMA) during an ECG stress test in patients with stable coronary artery disease and to assess the potential of these markers to detect exercise induced myocardial ischemia. PATIENTS AND METHODS: Patients with angiographically confirmed coronary atherosclerosis were included into the study. In all of them prognostic ECG stress test according to Bruce protocol was performed. The test was considered true positive (ischemia present) in case of significant ST-segment depression in the presence of significant coronary stenosis. The test was considered true negative (ischemia absent) when no significant ST depression was noted in the absence of significant coronary stenosis. In all patients echocardiography was performed and blood was drawn for NT-proBNP, IMA, serum albumin and creatinine before and within the first five minutes after exercise. RESULTS: 41 patients with unequivocal stress test result corresponding to coronary angiogram were included in the final analysis (out of 51 examined patients). 21 patients demonstrated ischemia during exercise, 20 did not. NT proBNP concentration was significantly higher after the stress test than before in the whole group: 127.9 (10.7-994.2) pg/ml and 110 (10.5-990.2) pg/ml respectively; p < 0.0001. NT-proBNP increase was higher in the ischemic than in the non-ischemic group; however, the difference was not statistically significant: deltaNT-proBNP 12.3 (1.0-172.3) pg/ml and 4.2 (1.0-77.1) pg/ml respectively; p = 0.09. This manifested itself in poor sensitivity and specificity of NT-proBNP in detecting exercise induced myocardial ischemia: 62 and 55% respectively (AUC 0.589). In the whole group the increase of NT-proBNP depended on baseline NT-proBNP concentration (r = 0.54; p = 0.0003), the magnitude of ST-segment depression (r = 0.38; p = 0.01), creatinine concentration (r = 0.34; p= 0.03) and history of myocardial infarcion: log deltaNT-proBNP in post-MI patients and in patients without prior MI 1.19 ( +/- 0.54) i 0.61 ( +/- 0.57) respectively; p = 0.004. In multiple regression analysis the only factor independently determining NT-proBNP increase during exercise was the history of myocardial infarction (beta = 0.342; p = 0.01) but not left ventricle ejection fraction. IMA decreased during exercise in all patients significantly--the mean value before and after exercise was 88.20 (7.72) and 78.05 (8.33) U/ml respectively; p = 0.0001. Decrease in IMA correlated only with increase in albumin concentration measured before and after exercise (r = -0.6; p < 0.0001). CONCLUSIONS: Exercise induced myocardial ischemia has little influence on NT proBNP increase. The test measuring it has therefore insufficient ability to detect exercise induced ischemia in stable coronary artery disease. In patients with stable coronary artery disease without severe impairment of left ventricular function the history of myocardial infarction is the main factor determining NT proBNP increase during exercise. Changes in serum albumin concentration during exercise seem to exclude the use of IMA in the assessment of exercise induced myocardial ischemia. PMID- 17340971 TI - [Prediction of adverse cardiac events in patients with acute anterior wall myocardial infarction treated with PCI]. AB - Despite common use of reperfusion therapy, particularly primary PCI during acute myocardial infarction, steadily increasing number of patients with low left ventricular ejection fraction, with heart failure (HF), requiring frequent rehospitalisation justifies the study establishing the best indices of prediction of major adverse cardiac events (MACE) occurrence. The aim of the study was to define the frequency of MACE (death, re MI, sVT, rehospitalisation for HF) in patients with acute anterior wall myocardial infarction in 6 month follow up and the factors determinatig its occurence. The 115 consecutive patients (86 males of age 57.7 +/- 11 yrs) with first anterior MI were studied. After successful PCI (TIMI 3) the angiographic assessment was performed (MBG 0-1 - no perfusion, MBG 2 3 - perfusion preserved). During first 48 hours 12-lead ECG was monitored in order to analyse the time to reduction of ST elevation in the lead with the highest elevation (deltatST 50%). On 2nd day LV function (LVEF and WMSI) and dyssfunctional segment perfusion (RPSI) were assessed. On 5th day Holter monitoring with arrhythmia and time domain parameters (SDNN, rMSSD) of heart rate variability were performed, on 30 day TWA test was done. RESULTS: During 180 follow-up 18 MACE occurred (3 death, 2 MI, 11 rehospitalisations for HF). In univariate analysis cigarette smoking, higher maximum troponin I value, LVEDV, LVESV, ST elevation sum, longer time to reduction of ST elevation, lower LVEF and RPSI, lack of microvessel integrity and positive TWA test had significant relationship with occurrence of MACE. The multivariate analysis of Cox proportional risk regression demonstrated that only lower value of RPSI and LVEF, longer time of ST elevation reduction in the lead with the highest ST elevation and positive TWA test were independent indices of MACE prediction. CONCLUSIONS: Cumulative evaluation of LVEF, indices of preserved perfusion and results of TWA test turned out to be the best predictors of MACE occurrence in 6 month follow up in patients after anterior MI treated with PCI. PMID- 17340972 TI - [Endoscopic septotomy treatment of Zenker's diverticulum]. AB - The Zenker's diverticulum is the pathology of pharyngo-esophageal region with its neck proximal to the cricopharyngeal muscle. The Zenker's diverticulum is the rare finding in upper endoscopy, but choice of treatment may bring some problems. Nowadays, the flexible endoscopy has been in focus of interest for treatment of Zenker's diverticulum. METHODS: Our first experience in management of Zenker's diverticulum include 40 patients, age 67-82 years old. All patients had symptoms such as dysphagia, aspiration pneumonia or sputum at night. The procedure consist of endoscopic incision of septum between esophageal lumen and diverticulum using argon beamer until its high was less than 0.5 cm. RESULTS: all patients became free of symptoms. Each patient complained of sore throat after treatment. No serious complications were observed. Only one case of retropharyngeal space emphysema and two cases of perforation were observed, both of them were treated with antybiotics and nasogastric tube feeding. CONCLUSION: It seems that this method is save and efficacious for treatment of Zenker's diverticulum. PMID- 17340973 TI - [Effectiveness of darbepoietin alfa in anemic patients with chronic kidney disease (CKD) in predialysis period]. AB - Patients with chronic kidney disease (CKD) often suffer from anemia due to erythropoietin deficiency. Anemia treatment with erythropoietin in patients with chronic kidney disease can effectively maintain hemoglobin target level > 11g/dl. In this study we presented the results of anemia treatment with darbepoietin alfa in 18 patients with chronic kidney disease (3-5 stage of CKD) in predialysis period. After 10 weeks of darbepoietin alfa administration at the dose 10 microg/week, hemoglobin serum level had increased over 11 g/dl in 15 patients. In the 3 patients serum hemoglobin level during the darbepoietin alfa treatment did not increased. Between 15 patients, in 4 after 10 weeks of darbepoietin alfa treatment at the dose 10 microg/week and in 7 after 15 weeks of the treatment at the dose 15 microg/2 weeks hemoglobin serum level had increased over 13 g/dl. After 2 months with out darbepoietin alfa treatment hemoglobin serum level had decreased but still maintain the target level 11 g/dl. darbepoietin alfa was well tolerated. The results of this study demonstrate that darbepoietin alfa administered s.c. once weekly or once other week at a small doses is effective in renal anemia treatment and comfortable for a patients. PMID- 17340974 TI - [Impact of chronic graft-versus-host disease on long-term outcome after allogeneic hematopoietic cell transplantation in adult acute lymphoblastic leukemia]. AB - Chronic graft-versus-host-disease (cGVHD) is a major cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT). However, it may be accompanied by graft-versus-leukemia (GVL) reaction contributing to decreased risk of relapse. The aim of this study was to evaluate the influence of cGVHD on outcome of adult acute lymphoblastic leukemia (ALL) patients treated with alloHCT. Fifty-five ALL patients, aged 24 (18-54) years, who survived without progression at least 100 days after alloHCT from HLA-identical sibling (n = 40, 73%) or an unrelated volunteer (n = 15, 27%) were included in the analysis. 24 patients 44% were given alloHCT in first complete remission, whereas the remaining 31 patients (44%) were in more advanced disease. The probability of overall survival (OS) and disease-free survival (DFS) equaled 57% and 48% at 8 years, respectively. Cumulative incidence of relapse and non-relapse mortality (NRM) was 39% and 13%, respectively. OS rate equaled 51% for patients without cGVHD, 94% for patients with limited cGVHD, and 38% for those with extensive cGVHD. In the respective subgroups relapse incidence was 60%, 9% and 0%, whereas the incidence of NRM equaled 3%, 6% and 62%. In multivariate analysis the lack of cGVHD was the most important factor associated with increased risk of relapse and deteriorated DFS. Extensive, but not limited cGVHD was associated with increased risk of NMR. Our findings confirm that in adults with ALL, cGVHD is accompanied by a strong GVL reaction. Induction of limited cGVHD may constitute the most effective prophylaxis of relapse in this group of patients. PMID- 17340975 TI - [Fungal peritonitis in patients on peritoneal dialysis]. AB - Fungal peritonitis is a serious complication causes significant morbidity and mortality for patients on peritoneal dialysis. We reviewed our fungal peritonitis cases to analyse clinical features, treatment and predisposing factors. METHODS: Records of all peritonitis episodes were reviewed. Fungal peritonitis was diagnosed based on positive fungal culture in suitable media of the effluent. RESULTS: Between January 2001 and June 2006, 98 patients were treated with peritoneal dialysis. During this period 102 peritonitis episodes was noticed, four of them (3,9%) was caused by fungi. The most common pathogen was Candida sp. Preceding treatment with broad-spectrum antibiotics was revealed in all cases, three of them due to bacterial peritonitis. One patient died due to sepsis, three was moved to hemodialysis. CONCLUSIONS: Fungal peritonitis is rare, but serious complication it patients treated with peritoneal dialysis. Preceding broad spectrum antibiotic therapy is the main risk factor for the development of this complication. Early Tenckhoff catheter removal and prophylaxis (antifungal treatment, education, coexisting diseases treatment) may be beneficial for peritoneal dialysis patients with fungal peritonitis. PMID- 17340976 TI - [Myocardial infarction after carbon monoxide exposure--a case report]. AB - We present the case of a patient with the myocardial infarction as the result of carbon monoxide poisoning. We consider that a careful electrocardiographic and enzymatic monitoring of all patients after CO exposure is important for early diagnosis and treatment of myocardial infarction, especially because the patients often do not complain of any chest pain and ischaemic features in an electrocardiogram are withdrawing rather fast. PMID- 17340977 TI - [Cardiotoxicity of anthracyclin antibiotics]. PMID- 17340978 TI - [Diagnostic importance of bronchoalveolar lavage (BAL) in internal diseases]. PMID- 17340979 TI - [Air trapping in high resolution computed tomography]. PMID- 17340980 TI - [Cardiac cachexia]. PMID- 17340981 TI - [Primary hyperhidrosis--an interdiscipline issue. Current therapeutic strategies for treating primary hyperhidrosis]. PMID- 17340982 TI - [Exposure to silica dust in the Polish construction industry]. AB - BACKGROUND: In the construction industry, free crystalline silica (FCS), mostly in the form of quartz, is in a very common use. Construction, especially repair and demolition works, are associated with emission of considerable amounts of FCS containing dusts. Studies concerning the work environment, carried out recently in other countries, indicate that exposure to quartz frequently exceeds hygiene standards, i.e. safety limits for workers' health. The aim of this study was to assess dust exposure of workers employed at selected workposts in the construction industry in Poland. MATERIAL AND METHODS: The Polish study was performed in a group of workers employed in large and small enterprises and involved in establishing new constructions and demolishing old buildings. The group comprised 43 workers, employed at 9 workposts, who underwent 107 measurements of dust concentrations, of which 78 measurements were included in the analysis. At each workpost, concentrations of inhalable and respirable dusts were measured with the filtration and gravimetric method. Individual dust dosimeters were used to collect air samples and infrared spectrometry to determine concentrations of FCS dusts in samples of inhalable and respirable dusts. An identification analysis of dust samples was performed with use of X-ray diffraction. RESULTS: The results of the study show that geometric means of inhalable dust concentrations fell within a wide range from 2.1 (concrete mixer operator, plasterer) to 66.0 mg/m3 (laborer engaged in hand demolition), and those of respirable dust at the same workposts ranged from 0.4 to 16.2 mg/m3, respectively. Quartz was present in the majority of construction materials applied, and its concentration in inhalable dusts ranged from 7 to 13 mg/m3. CONCLUSIONS: It was found that dust concentrations exceeded hygiene standards at most of the workposts. Particularly high concentrations were observed at the workposts of surface abrasive grinders-coat finishers and workers engaged in drilling and hammering wholes. In conclusion, the need to use technical means, primarily personal respiratory protectors, to reduce dust concentrations should be strongly stressed. PMID- 17340983 TI - [Assessment of electromagnetic fields intensity emitted by cellular phone base stations in surrounding flats--a preliminary study]. AB - BACKGROUND: A rapid development of mobile telecommunications (MT) has resulted in an increased concern about possible detrimental health effects of electromagnetic fields (EMFs) emitted by MT systems, and by MT base stations in particular. Research into EMFs effects on the health of inhabitants living in their vicinity requires first of all a solid assessment of the exposure level. Up to now, the reports in this field have been rather scant. This article presents the results of preliminary measurements of EMFs fields in selected flats around selected base stations in the city of Lodz. MATERIAL AND METHODS: Measurements of electric field strength, E, to assess EMF exposure were based on the standard procedures currently in force in Poland. As the study is regarded as a preliminary one, the measurements were conducted in buildings with the expected largest radiation. RESULTS: The measurements show that in the flats located up to 500 m from the base station, EMFs are within the limits specified by relevant Polish regulations on the general public and environmental protection. It was also observed that in a few (less than 10%) flats the field with E exceeded 0.8 V/m. CONCLUSIONS: The results show that there are no correlations between electric field strength and distance between the flat and the base station. Therefore, the distance from the base station cannot be used to represent the exposure rate; to determine the latter, EMF measurements are necessary. PMID- 17340984 TI - [Diagnostics of occupational voice diseases following the amendment of the Polish Occupational Diseases Certification Act]. AB - BACKGROUND: The aim of the study was to assess whether the amended Polish Occupational Diseases Certification Act of 2002 has made an impact on the medico legal process of the occupational voice diseases certification. MATERIAL AND METHODS: Nationwide reports on the number and types of occupational diseases diagnosed in Poland in 1999-2004, and the medical records of 267 teachers diagnosed for the occupational voice organ disease were analyzed. RESULTS AND CONCLUSIONS: A 4-fold gradual and continuous reduction (from 3521 to 881 cases) in the number of registered occupational voice diseases was noted in 1999-2004, which was not really associated with the date the amended Act came into force. The patients challenging the first instance refusals issued after 2002 were characterized by significantly worse phoniatric and videostroboscopic indices than those consulted before that date. Before 2002, the percentage of the second instance positive decisions, changing the first instance refusals was over 16%, while after 2002 the corresponding number was only 5%. This indicates that a consensus of decisions issued by the first and second instances has significantly increased since the amended Act came in effect. PMID- 17340985 TI - [Contact allergy to fragrances]. AB - BACKGROUND: The incidence of allergy induced by fragrances, leading mostly to the development of contact dermatitis and urticaria chronica, has been growing in a large number of countries. In general, allergy is of non-occupational nature, however, it can also have traits of occupational exposure. The fragrance mix is used in screening for allergy to aromas, but it frequently produces false positive or false negative results of the test. The aim of the study was to assess whether the fragrance mix is suitable for detecting allergy to aromas in persons with suspected occupational allergy and also to analyze types of allergy to separate fragrances. MATERIAL AND METHODS: In a group of 1937 patients diagnosed in the Nofer Institute of Occupational Medicine in Lodz, the incidence of allergy to fragrance mix was assessed. They underwent dermatological examinations and tests with use of the European standard kit (Chemotechnique Diagnostics, Malmo, Sweden) in the years 2000-2005. In addition, in the group of patients with positive tests, the type of allergy to individual aromas was analyzed using fragrance series (Chemotechnique Diagnostics, Malmo, Sweden). RESULTS: The positive reaction to fragrance mix was found in 99 (5.1%) patients (women--5.2% and men--4.9%). In 57.6% of patients, allergy to balsam of Peru was also observed. Allergy to at least one aroma was diagnosed in 82 (72%) persons tested with an expanded fragrance series. In the remaining 23 (28%) patients, patch tests proved to be false positive. In the latter group, 17 patients showed negative results of the test to balsam of Peru. In the study group, 65% of patients reacted to 1, 2 or 3 and 36% to more aromas. The following allergens sensitized most frequently: cynnamic alcohol, hydroxycitronellal, cinnamic aldehyde, isoeugenol, eugenol, Ylang-Ylang oil, oakmoss absolute, and jasmine. Allergic contact dermatitis was diagnosed in 69.7%, urticaria chronica in 5.1% of patients, atopic dermatitis in 4%, whereas in 21.2% no skin lesions were observed. CONCLUSIONS: The results of the study confirmed observations of other authors that the usefulness of fragrance mix in the diagnosis of allergy to aromas is limited (a high number of false positive results of skin tests). We noticed that a combined reaction to fragrance mix and balsam of Peru is helpful in diagnosis in persons whom a complete allergic diagnosis cannot be performed. We also found less frequent hypersensitivity to oakmoss absolute and more frequent to cinnamic aldehyde and alcohol, hydroxycitronellal, eugenol, isoeugenol in Lodz than in studies reported by other authors. PMID- 17340986 TI - [Critical evaluation of reporting on postexposure skin damage incidents and its consequences for Polish health workers]. AB - BACKGROUND: The principles of uniform reports on infections with HBV, HCV, HIV due to occupational exposure have not yet been established in Poland. Usually, reporting on such incidents is governed by internal rules of individual health care institutions. The aim of the study was to assess the possibility of obtaining data on postexposure incidents among health care workers in different voivodeships (regions) and to identify a group of persons who most frequently reported such cases in a given calendar year. MATERIAL AND METHODS: Nineteen medical centers from all 16 voivodeships were invited to participate in the study. The main condition to be enrolled in the study was to provide full postexposure prophylaxis log. RESULTS AND CONCLUSIONS: In all, 8 centers from 8 voivodeships were enrolled in the final study. Only in 4 voivodehips, completely centralized postexposure prophylaxis logs were in operation. Women with secondary education (nurses) formed the major group of exposed persons. Exposure incidents occurred most frequently in wards or operation rooms while performing medical procedures or immediately after. Blood collection predominated among various kinds of exposure. The majority (75.7%) of health workers underwent full vaccination program against HBV. The analysis revealed large differences in exposure reporting between individual voivodeships. Sometimes they made it even difficult to complete full demographic data concerning exposed persons. Therefore, a universal tool of nationwide system should be elaborated. Such a system (an example is presented by the authors), regularly verified, might provide grounds for a wider analysis of postexposure prophylaxis efficacy, details concerning exposure incidents and their consequences in the future. This may greatly contribute to the reduction of exposure rates among health care workers. PMID- 17340987 TI - [Concentrations of natural 226Ra and 222Rn radioisotopes in the water from deep well intakes in the vicinity of Lodz]. AB - BACKGROUND. The towns of Zgierz, Ozorkow, Strykow and Glowno are located in the central part of Poland, 10 to 30 km to the north of Lodiz. Large surface water reservoirs are not available in that region, and the inhabitants of this region are supplied with drinking water from deep water sources. Literature data show that water from deep wells may contain various radionuclides, such as radium 226Ra or radon 222Rn, and their activity levels depend, among others, on the age of the geologic formation the water comes from. MATERIAL AND METHODS: An emanation technique employing a low-background system consisting of scintillation chamber with two photomultipliers operating in the coincidence arrangement was used to measure radium and radon concentrations. RESULTS: Radium-226 at levels above the detection level (9 Bq/m3) of the measurement method were not detected in any of the examined deep water sources. Water-solved radon-222 was detected in all tested samples. The measured activities were within the range of 1 kBq/m3 to 13 kBq/m3. CONCLUSIONS: Assuming the maximum concentration value, it is estimated that an annual dose received by the population drinking that water is 0.04 mSv, which is below the value of 0.1 mSv recommended by the World Health Organisation. PMID- 17340988 TI - [Secondary nephropathies in occupational health practice. II. Kidney disorders induced by drug and contrast media]. AB - Nowadays, drug induced kidney disorders have become a frequent health problem. Iatrogenic nephropathies are manifested by a wide variety of clinical symptoms, including acute renal failure (about 20%), one of the major negative prognostic factors in internal diseases. Occupational kidney disorders induced by exposure to chemical toxins at a work place may coincide with those caused by drugs. This comorbidity can increase the risk of their progression to further deterioration of renal function, leading finally to long lasting work disability among employees. In this paper, we analyzed the mechanism by which major nephrotoxic drugs (e.g., antibiotics, non-steroidal anti-inflammatory agents, contrast media and angiotensin converting enzyme inhibitors) exert their effect on kidneys. Special attention was paid to over-the-counter medications, which are available in many countries, and thus are frequently abused by the working population. The early identification of non-occupational causes of kidney disorders helps avoiding accumulation of nephropathies of different origin, being of great practical value. PMID- 17340989 TI - [Diabetes mellitus: an issue for medical certification]. AB - Diabetes mellitus is a progressive and complex disorder that is difficult to treat effectively in the long- term. The number of people with diabetes and other glucose impairments is increasing due to population growth, aging, urbanization, and physical inactivity. In Poland, it has been estimated that there are about two million people with diabetes, half of them are not aware of their illness. Hypoglycemia is the most common and potentially most serious adverse effect of pharmacotherapy in diabetes, regardless of the model of treatment. The potential risk factors for severe hypoglycemia in subjects with treated diabetes are: physical activity, lifestyle circumstances, irregular eating habits, drug interaction or shift work. Therefore, there is an urgent need to set criteria and recommendations for medical certification of individuals working or taking up the job connected with public safety, where diabetes could have a particularly important and dangerous impact. PMID- 17340990 TI - [Post-accident injuries to the locomotor system and divergent medical opinions on the percentage of health loss in insured persons]. AB - The authors present the results of an analysis of certification rules applied by insurance companies for the purpose of medical expertise. It was found that the percentage of health loss was very frequently understated by insurance companies as compared with that decided by Polish courts. This mostly applied to diseases of musculoskeletal system and consequences of head injuries, which proved to be profitable for insurance companies. It was also common for medical experts working for insurance companies to use the lowest possible rates in estimating the loss of health. The authors emphasized the need to unify the rules and criteria for determining the percentage of health loss, or to inform insurance applicants about the fact that insurance companies have their own rules, which differ from those applied by courts. PMID- 17340991 TI - [Psychological effects of road accidents: a challenge for public health]. AB - The authors discuss psychological consequences of road accidents and the need for providing support for the victims and their families. The most common psychological effects include mental health problems, increased use of psychotropic drugs, and difficulty in performing occupational functions. Therefore, it is necessary to remodel the system of traffic safety and supplement it with a comprehensive system of support for both direct victims of accidents and their close relatives. To reach this goal, we need to develop optimal conditions for multidisciplinary research to investigate the effects of road accidents in Poland. This would make it possible to design effective psychological treatment and develop an institutional system for relevant support. However, some preventive measures can be taken right now, e.g., early intervention for severely injured victims during their hospital stay or providing support for non-injured victims and their families. PMID- 17340992 TI - [The frequency of the occurrence of genes ermA, ermB, ermC and msrA/B among methicillin-resistant Staphylococcus aureus strains resistant to erythromycin]. AB - The group of 50 clinical MRSA strains resistant to MLS-B was examined for the presence of ermA, ermB, ermC, msrA/B genes by using PCR. Gene ermA was found in 43 strains (86%). 20 of ermA strains demonstrated inducible whereas 23 constitutive type of expression. The gene ermC was present in 15 of examined MRSA strains (30%). The expression of the gene was inducible in the case of 9 and constitutive in the case of 6 of the strains. The msrA/B gene was present in the case of 5 strains (10%). The ermB gene was not detected among the investigated strains. PMID- 17340993 TI - [Presence of enterotoxin C and toxic shock syndrome toxin--1 (TSST-1) genes in population of Staphylococcus aureus phage type 187]. AB - The aim of this study was to examine whether Staphylococcus aureus of phage type 187 possess the genes of enterotoxins and toxic shock syndrom toxin. Sixteen phage type 187 strains were isolated from the hospital patients (12) and the carriers (4) in twelve medical centres in Poland during 1991 and 2005. Biotyping, phage typing, antibiotic susceptibility, detection of the genes of enterotoxins (sea--sed) and toxic shock syndrome toxin (tst) was tested. The results of this study showed that all staphylococci of phage type 187 belonged to the human biotype (A) and appeared to be sensitive to all of the tested antibiotics, including methicillin (MSSA). Almost all of them (93.8%) had the enterotoxin C gene and TSST-1 gene. This fact allows to consider them the strains of potentially high virulence. PMID- 17340994 TI - [MIC and MBC of quinupristin/dalfopristin of erythromycin-resistant MRSA strains isolated from clinical specimens]. AB - The MICs and MBCs of quinupristin/dalfopristin were determined for 22 clinical strains MRSA with inducible type of resistance to MLS-B and for 15 of their derivatives with constitutive resistance to MLS-B. For MRSA strains with inducible resistance to MLS-B the obtained results for quinupristin/ dalfopristin were: MIC50 = 0.25, MIC90 = 0.5, MBC50 = 1.0 and MBC90 = 1.0. Mutants of the same strains characterized with the following values for quinopristin/dalfopristin: MIC50 = 0.5, MIC90 = 1.5, MBC50 = 4.0 and MTC90 = 8.0. PMID- 17340995 TI - [Prevalence of antibodies to Francisella tularensis in forest workers from different regions of Poland]. AB - In the present study we evaluate the prevalence of antibodies to F. tularensis in 480 serum samples obtained from healthy forest workers from different regions of Poland. The investigations were performed using the tube agglutination test and ELISA. The cut-off limit of serum antibodies was set at mean antibody titre determined in the sera of 115 blood donors exceeded by three standard deviations. In none serum samples we detected antibodies to F. tularensis by tube agglutination test. Of the 480 tested sera IgA antibodies were detected by ELISA in 4.6%, antibodies IgG in 3.8% and antibodies IgM in 2.70% serum samples. The results of our study showed that antibodies to F. tularensis were slightly, but not statistically significant, more often diagnosed in healthy forest workers than healthy blood donors. PMID- 17340996 TI - [Prevalence of pathogenic genes of Campylobacter jejuni isolated from humans in Poland between 2003-2005]. AB - Campylobacter jejuni is an important cause of food-borne gastroenteritis and enteritis in humans in many developed countries. Several C. jejuni virulence determinants have been identified. The purpose of our experiments was to determine the prevalence of virulence and toxin genes cadF, flaA, cdtA, cdtB, cdtC, cdtABC, virB11 among 102 C. jejuni isolates isolated in Poland between 2003 and 2005 from humans with diarrhea. The PCR analysis of the strains revealed the presence of the flaA and the cadF genes among all C. jejuni isolates. Detection rates for the cdtA, cdtB, cdtC and cdtABC cluster genes were 98, 96, 92 and 88% respectively. The virB11 gene was found in only 3% of the isolates. The high prevalence of cadF, flaA and cdt genes demonstrated that these genes may play an important role in C. jejuni virulence. Further research is necessary to clarify the importance of the virB11 gene in the pathogenesis of infections with C. jejuni strains in humans. PMID- 17340997 TI - [Lipopolysaccharides and lipoteichoic acids stimulate rat mast cells to cysteinyl leukotriene synthesis]. AB - We have investigated the ability of lipopolysaccharides (LPS) and lipoteichoic acids (LTA) to induce rat peritoneal mast cells to degranulation and histamine release, and to cysteinyl leukotriene (LT) generation. We have stated that LPS Salmonella Enteritidis, LPS Escherichia coli O111:B4 and LPS E. coli O55:B5 did not activate rat mast cells to degranulation and histamine release. However, LPSs induced LT synthesis and secretion; the strongest stimulant to generation of LT was LPS E. coli O55:B5 (concentration of LT in supernatant was 830.5 +/-15.2 pg/ml). We have also observed that LTA Staphylococcus aureus and LTA Bacillus subtilis stimulated rat mast cells to degranulation and histamine secretion, even though the percentage of the releases histamine was relatively low (10.0 +/- 1.4 and 10.4 +/- 5.4 at antigen concentration, respectively). At the same time, LTA of both of the bacterial species strongly activate LT generation by mast cells (concentrations of LT in supernatants were 777.9 +/- 11.2 pg/ml and 734.0 +/- 38.3 pg/ml, respectively, at the antigen concentration 50 ng/ml). Our results have shown that LPS oraz LTA activate rat mast cells to secretion of proinflammatory mediators. PMID- 17340998 TI - [Susceptibility to chemotherapeutics and the occurrence of metallo-beta lactamases in hospital Pseudomonas aeruginosa strains]. AB - The aim of the study was evaluation of susceptibility of Pseudomonas aeruginosa strains isolated from patients hospitalized in different wards of Rydygier's Hospital in Krakow in 2005. Bacteria were identified on the basis of typical morphology confirmed by Gram-staining microscopy and by biochemical tests--ID 32 GN strips using ATB system (bioMerieux, France). The susceptibility of all isolates to a panel of antimicrobial agents was performed using disk diffusion method. The highest in vitro activity against clinical strains demonstrated ceftazidime (88.6% of susceptible strains) while the lowest in vitro activity against clinical strains demonstrated imipenem (50.4% of susceptible strains). It was also observed that 40.2%(53) of strains were resistant to meropenem and imipenem. Carbapenem resistant P aeruginosa strains were tested for MBL production. We performed disk synergy test for MBL detection with EDTA, 2-MPA and ceftazidime, imipenem. The presence of a distorted inhibition zone was interpreted as a positive result for MBL production. Positive results of disk synergy tests were confirmed by Etest MBL strips. Metalo-beta-lactamases were detected in 13 isolates resistant to carbapenems. PMID- 17340999 TI - [Nosopharyngeal microflora in ambulatory treated children and adults with upper respiratory tract infections]. AB - Upper respiratory tract consists resident and transient bacterial microflora, which in appropriate condition can cause infection. Bacteriological study was performed among 201 patients with upper respiratory tract infections treated in ambulatory. From nasal and pharyngeal swabs Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Streptococci group A, B, C, G were isolated. Antibiotic susceptibility testing of isolated strains was performed using CLSI criteria. All isolated strains of streptococci were susceptible to penicillin; some of them demonstrated resistance to macrolides and lincosamides. Few isolated strains of H. influenzae demonstrated resistance to penicillin and cotrimoxazole. Azitromycin resistant strains were not detected. All isolated strains of M. catarrhalis were beta-lactamase positive and demonstrated resistance to penicillin. Strains of methicillin sensitive S. aureus (MSSA) were isolated most frequently from pharyngeal swabs (35.4%) and S. pneumoniae (33.3)--from nasal swabs. PMID- 17341000 TI - [Evaluation of Agar Candida ID2 (bioMerieux) a chromogenic medium for yeasts differentiation]. AB - Invasive diagnostic and therapeutic methods, widespread antibiotic therapy and rising percent of the immunocompromised patients cause incrementation of frequency of occurrence of the yeast infection. C. albicans is the most commonly isolated species of Candida from clinical samples. However, recently growth of frequency of isolation Candida non - albicans from clinical specimens have been observed. Yeast-like fungi different from C. albicans have become serious clinical problem. Conventional methods of identification of the yeast-like fungi carry away a lot time enough. Employment of chromogenic agar shortens latency on result. We decided to examine the usefulness ofAgar Candida ID2 (CAN2) (bioMerieux) in the identification of Candida species. The subjects within the study were 146 of Candida spp strains which were isolated from the clinical specimens of patients hospitalized at the University Hospital in Bydgoszcz. Germ tube test. Api 20C AUX test (bioMerieux) and Agar Candida ID2 (bioMerieux) were used. We have ascertained correspondence of identifying species amounted to 82.2% of analyzed Candida species between API 20C AUX test and kind of growth on CAN2 medium. Divergence of results received between CAN2 medium and API 20C AUX test suggests necessity of conducting of verification data with other methods. In conclusion, our study shows that Agar Candida ID2 is an effective medium for the isolation yeast-like fungi and in preliminary identification of Candida species direct from clinical materials. PMID- 17341001 TI - [Influence of incubation conditions on cell surface hydrophobicity of Candida species fungi]. AB - Cell surface hydrophobicity (CSH) is considered to be one of several virulence factors of Candida yeast-like fungi. The aim of the study was a measurment of hydrophobic properties of Candida sp. depending on growth conditions. A total of 139 strains of Candida (80 - C. albicans and 59 - C. non-albicans) were examined. The method of salt aggregation test (SAT) was used. The strains were cultured on three different media, in two variants of incubation temperature and time. The incubation temperature and microbiological medium affected CSH of just C. albicans strains. The influence of incubation time on CSH of examined species of Candida was not occurred. There was a strong correlation between CSH and species of Candida demonstrated in the study Hydrophobic properties were more frequent and stronger among strains of C. non-albicans than C. albicans species. The results of the study indicates that CSH of Candida spp. is a dynamic feature. The ability to change surface properties may play a role in pathogenesis of candidosis. PMID- 17341002 TI - In memory of Hans Selye (1907-1982), the father of the stress concept. PMID- 17341003 TI - Ginkgo biloba special extract in dementia with neuropsychiatric features. A randomised, placebo-controlled, double-blind clinical trial. AB - BACKGROUND: In previous trials of the Ginkgo biloba special extract EGb 761 improvements in cognitive functioning and behavioural symptoms were found in patients with aging-associated cognitive impairment or dementia. This trial was undertaken to assess the efficacy of EGb 761 in mild to moderate dementia with neuropsychiatric features. METHODS: Double-blind trial including 400 patients aged 50 years or above with Alzheimer's disease (AD) or vascular dementia (VaD), randomized to receive EGb 761 or placebo for 22 weeks. Patients scored below 36 on the Test for the Early Detection of Dementia with Discrimination from Depression (TE4D), between 9 and 23 on the SKT test battery and at least 5 on the Neuropsychiatric Inventory (NPI). RESULTS: There was a mean -3.2-point improvement in the SKT upon EGb 761 treatment and an average deterioration by +1.3 points on placebo (p < 0.001, two-sided, ANOVA). EGb 761 was significantly superior to placebo on all secondary outcome measures, including the NPI and an activities-of-daily-living scale. Treatment results were essentially similar for AD and VaD subgroups. The drug was well tolerated; adverse events were no more frequent under drug than under placebo treatment. CONCLUSION: The data add further evidence on the safety and efficacy of EGb 761 in the treatment of cognitive and non-cognitive symptoms of dementia. PMID- 17341004 TI - Proof of systemic safety of a lidocaine ointment in the treatment of patients with anorectal pain. AB - OBJECTIVE: The aim of the study was to demonstrate that repeated anorectal administration of a 5% lidocaine ointment (CAS 137-58-6; LidoPosterine Salbe, Posterisan akut Rektalsalbe) in the treatment of patients with acute anorectal pain does not result in systemically efficacious plasma concentrations of lidocaine. PATIENTS AND METHODS: In an open single-center study 24 male or female patients with anorectal pain due to hemorrhoids, anal fissures, fistulas or proctitis administered lidocaine ointment as a single anorectal dose (2.5 g ointment corresponding to 125 mg lidocaine) followed by repeated administration (2.5 g ointment t.i.d.) for 4 days. Safety evaluation was performed with respect to plasma concentrations of lidocaine, vital signs, electrocardiogram (ECG), physical findings and adverse events. Blood samples were drawn prior to the first single administration and at 13 time points over the first 24 h in order to create a pharmacokinetic profile. Blood samples were also drawn prior to administration of the last dose on day 5 and thereafter using the identical time points for blood sampling as on day 1. Vital signs and ECG were recorded immediately before and 1 and 4 h after the first and last administration, respectively. Adverse events and skin tolerability were also recorded at predefined times during the study period. RESULTS: After a single dose of 125 mg lidocaine the average extent of exposure in terms of the AUC(tau,sd) during a 6 h dosage interval amounted to 397.7 ng/ml x h (geometric mean). C(max,sd) reached a mean value of 131.8 ng/ml (geometric mean). Only a minor accumulation of the lidocaine plasma concentrations was observed after multiple dose application. The geometric mean of the AUC(tau,md) (503.8 ng/ml x h, tau = 6 h) and the geometric mean of C(max,md) (145.9 ng/ml) were slightly higher than the corresponding single dose values. The AUC accumulation ratio was calculated as 127% (90% CI: 108-148%) and the C(max) accumulation ratio reached 120% (90% CI: 101-139%). Plasma peak concentrations of lidocaine in all subjects remained with a sufficient safety margin below the minimal effective therapeutic plasma concentration (1.5 microg/ml) as well as by an order of magnitude below toxic concentrations (5 microg/ml). There were neither unexpected, serious nor severe adverse events. There were no clinically relevant findings with respect to vital signs and ECG. CONCLUSIONS: Repeated anorectal administration of a 5% lidocaine ointment proved to be safe with respect to systemic plasma concentrations of lidocaine and vital signs. PMID- 17341005 TI - Clinical efficacy of benidipine for vasospastic angina pectoris. AB - BACKGROUND: Most patients with vasospastic angina who have no significant organic coronary arterial stenosis are well controlled by medical therapy and the prognosis is almost satisfactory. Calcium channel (Ca) blockers are used as the first choice and effective agents for vasospastic angina pectoris. However, they do not always work well. Some uncontrolled coronary vasospasms would happen to cause prolonged occlusion of coronary artery resulting in myocardial infarction, life-threatening arrhythmias and sudden death. Therefore, it is very important to pay attention to such a refractory coronary spasm and choose the most effective agent out of Ca blockers for the treatment of each patient with vasospastic angina attacks. This study was designed to evaluate the anti-vasospastic efficacy of benidipine, a long acting dihydropyridine (DHP) Ca blocker, in patients with other Ca blockers-resistant angina. METHODS: Patients treated with diltiazem but not enough to control angina attacks were enrolled in the present study. Treatment with diltiazem (CAS 33286-22-5, 42399-41-7) was changed to treatment with benidipine (CAS 91599-74-5) and the parameters such as angina frequency, duration, blood pressure, heart rate, electrocardiogram and hematological parameters (serum NO(x), plasma cGMP) were measured and compared. RESULTS: Fifteen patients with vasospastic angina were enrolled. After switching from diltiazem to benidipine, angina attacks were completely disappeared in six patients. Although the frequency was not decreased, the average duration of attacks was shorter than before in three patients. Four patients did not improve and two patients obviously worsened. In the improved nine patients, serum nitrite/nitrate (NO(x)) levels showed a significant increase from 37.6 +/- 15.3 to 54.5 +/- 26.7 pmol/L (p < 0.05) and cGMP levels subsequently elevated from 2.2 +/- 0.8 to 2.5 +/- 0.6 micromol/L (p = 0.05) after benidipine therapy started. Adverse effects such as hypotension and bradycardia were not observed. CONCLUSION: This study suggests that benidipine may be helpful in Japanese patients with vasospastic or variant angina pectoris, if diltiazem was not successful. PMID- 17341006 TI - Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents. A single-blind clinical investigation. AB - Berberine (BERB) and a combination (COMB) of berberine (CAS 2086-83-1) with policosanol (CAS 557-61-9), red yeast extract (containing monacolin, CAS 557-61 9), folic acid and astaxanthin were orally administered daily for 4 weeks to 40 subjects with moderate dyslipidemias divided in two parallel groups each of 20 subjects. Total cholesterol (TC), LDL, HDL, Non HDL, ApoB, ApoA, Lp(a) and triglycerides (TG) were measured before and at the end of treatments. BERB and COMB significantly reduced TC (respectively by 16% and 20%), LDL (by 20% and 25%), ApoB (by 15% and 29%) and TG (by 22% and 26%), and increased HDL (by 6.6% and 5.1%). Adverse events or impairments of liver transaminases or of CPK were not observed. In conclusion, food supplements containing natural products such as berberine, policosanol, red yeast extracts, folic acid and astaxanthin could be a useful support to diet and life style changes to correct dyslipidemias and to reduce cardiovascular risk in subjects with moderate mixed dyslipidemias. PMID- 17341007 TI - Preclinical toxicity and pharmacokinetics of the Bruton's tyrosine kinase targeting anti-leukemic drug candidate, alpha-cyano-beta-hydroxy-beta-methyl-N- (2,5-dibromophenyl) propenamide (LFM-A13). AB - The leflunomide (CAS 75706-12-6) metabolite (LFM) analog alpha-cyano-beta-hydroxy beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13, DDE-28, CAS 244240-24-2) is a rationally-designed specific inhibitor of the TEC family protein tyrosine kinase, Bruton's tyrosine kinase (BTK). LFM-A13 exhibited favorable pharmacokinetics in CD-1 mice, BALB/c mice, rats, and dogs. The intraperitoneal bioavailability was estimated to be -100%, while the oral bioavailability was 30%. LFM-A13 enters, but does not bind to multiple tissues followed by a rapid elimination from most of the tissues. Limited distribution of LFM-A13 to extravascular tissues and its corresponding low volume of distribution could be attributed to its plasma protein binding. LFM-A13 was not toxic to mice, rats, or dogs at daily dose levels as high as 100 mg/kg. LFM-A13 formulated as a suspension and hard gelatin capsules for oral administration showed a rapid absorption and favorable pharmacokinetic features. These preclinical research studies provide the basis for future pre-IND studies and clinicaldevelopment of LFM-A13 as an intravenously or orally administered new anti-leukemia agent targeting BTK. PMID- 17341008 TI - Comparison of different perrmeation enhancers on topical ketoconazole formulations. AB - The clinical efficacy of five ketoconazole (CAS 65277-42-1) topical formulations (three gels and two creams) was evaluated in 50 patients suffering from fungal infections in an open uncontrolled pilot study. Each formulation contained selected permeation enhancers providing high permeability in vitro. The patients were randomly divided into five groups each of ten persons. Each group was assigned to a selected topical formula which was applied to the diseased skin twice daily for four weeks or until complete clinical improvement. The clinical evaluation of treatment effects was based on the following criteria: size of lesion, erythema, scaling and severity of itching (four grades each). The patients were considered cured after the disappearance of these clinical symptoms and negative potassium hydroxide and Wood's light examination tests during the follow-up period. The results showed that the overall therapeutic response to the treatment was 96.7% and 93% for the hydroxypropylmethyl cellulose gel containing menthol and sodium carboxymethyl cellulose gel containing isopropyl myristate, respectively. Creams (w/o and o/w) achieved 90% and 87% improvement after 2.5 weeks, respectively. The lowest clinical response (86.5% improvement) with the longest duration of treatment (3 weeks) was observed with sodium carboxymethyl cellulose gel containing oleic acid. PMID- 17341010 TI - Going against the grain: regulatory focus and interference by task-irrelevant information. AB - In this study it is argued that a perceiver's regulatory focus (promotion or prevention) influences the amount of attention allocated to processing stimuli from the environment. Results of two experiments, employing an interference task and using different manipulations of regulatory focus, supported this idea. More attention was allocated to stimuli incompatible with the activated focus (promotion-negative stimuli, prevention-positive stimuli). The incompatible stimuli therefore interfered more with an ongoing task than compatible stimuli. These results are discussed in terms of processing efficiency and integrated with motor-compatibility effects. PMID- 17341011 TI - A multitrait-multimethod validation of the Implicit Association Test: implicit and explicit attitudes are related but distinct constructs. AB - Recent theoretical and methodological innovations suggest a distinction between implicit and explicit evaluations. We applied Campbell and Fiske's (1959) classic multitrait-multimethod design precepts to test the construct validity of implicit attitudes as measured by the Implicit Association Test (IAT). Participants (N = 287) were measured on both self-report and IAT for up to seven attitude domains. Through a sequence of latent-variable structural models, systematic method variance was distinguished from attitude variance, and a correlated two-factors per-attitude model (implicit and explicit factors) was superior to a single factor-per-attitude specification. That is, despite sometimes strong relations between implicit and explicit attitude factors, collapsing their indicators into a single attitude factor resulted in relatively inferior model fit. We conclude that these implicit and explicit measures assess related but distinct attitude constructs. This provides a basis for, but does not distinguish between, dual process and dual-representation theories that account for the distinctions between constructs. PMID- 17341012 TI - Developmental fractionation of working memory and response inhibition during childhood. AB - The lateral prefrontal cortex (LPFC) plays a major role in both working memory (WM) and response inhibition (RI), which are fundamental for various cognitive abilities. We explored the relationship between these LPFC functions during childhood development by examining the performance of two groups of children in visuospatial and auditory WM tasks and a go/no-go RI task. In the younger children (59 5- and 6-year-olds), performance on the visuospatial WM task correlated significantly with that in the auditory WM task. Furthermore, accuracy in these tasks correlated significantly with performance on the RI task, particularly in the no-go trials. In contrast, there were no significant correlations among those tasks in older children (92 8- and 9-year-olds). These results suggest that functional neural systems for visuospatial WM, auditory WM, and RI, especially those in the LPFC, become fractionated during childhood, thereby enabling more efficient processing of these critical cognitive functions. PMID- 17341013 TI - A curious belief-bias effect: reasoning with false premises and inhibition of real-life information. AB - Many studies have shown that inferential behavior is strongly affected by access to real-life information about premises. However, it is also true that both children and adults can often make logically appropriate inferences that lead to empirically unbelievable conclusions. One way of reconciling these is to suppose that logical instructions allow inhibition of information about premises that would otherwise be retrieved during reasoning. On the basis of this idea, we hypothesized that it should be easier to endorse an empirically false conclusion on the basis of clearly false premises than on the basis of relatively believable premises. Two studies are presented that support this hypothesis. PMID- 17341014 TI - Affective priming of nonaffective semantic categorization responses. AB - Recent studies have shown that robust affective priming effects can be obtained when participants are required to categorize the targets on the basis of their valence, but not when participants are asked to categorize the targets on the basis of nonaffective features. On the basis of this pattern of results, it has been argued that affective priming is due to processes that operate at a response selection stage rather than to processes that operate at an encoding stage. We demonstrate (a) that affective priming of nonaffective semantic categorization responses can be obtained when participants assign attention to the affective stimulus dimension, and (b) that affective priming in the standard evaluative categorization task is strongly reduced when participants assign attention to nonaffective stimulus features. On the basis of these findings, we argue (a) that processes operating at an encoding stage do contribute to the affective priming effect, and (b) that automatic affective stimulus processing is reduced when participants selectively attend to nonaffective stimulus features. PMID- 17341015 TI - Perception of whether an object can be carried through an aperture depends on anticipated speed. AB - We investigated whether anticipated speed of locomotion through an aperture influences perception of whether an object can be carried through that aperture. Participants reported whether they would be able to carry objects through an aperture (a) if they were to attempt to walk through the aperture and (b) if they were to attempt to run through the aperture. Furthermore, they did so when the object was held but not seen and when the object was seen but not held. In general, perception was influenced by object width and by anticipated speed but not by perceptual modality. Perceptual boundaries occurred at smaller object widths when participants anticipated running through the aperture than when they anticipated walking through the aperture. The results build on work showing that perception of affordances is influenced by kinetic potential as well as geometric properties and that perception may be supported by the detection of modality neutral stimulation patterns. PMID- 17341016 TI - False memory in a short-term memory task. AB - The Deese/Roediger-McDermott (DRM; Roediger & McDermott, 1995) paradigm reliably elicits false memories for critical nonpresented words in recognition tasks. The present studies used a Sternberg (1966) task with DRM lists to determine whether false memories occur in short-term memory tasks and to assess the contribution of latency data in the measurement of false memories. Subjects studied three, five, or seven items from DRM lists and responded to a single probe (studied or nonstudied). In both experiments, critical lures were falsely recognized more often than nonpresented weak associates. Latency data indicated that correct rejections of critical lures were slower than correct rejections of weakly related items at all set sizes. False alarms to critical lures were slower than hits to list items. Latency data can distinguish veridical and false memories in a short-term memory task. Results are discussed in terms of activation-monitoring models of false memory. PMID- 17341017 TI - Cognitive processes in the Extrinsic Affective Simon Task: a task-set switching account of EAST effects. AB - Recently, De Houwer (2003) introduced the Extrinsic Affective Simon Task (EAST) as a new procedure for the indirect assessment of attitudes. In the present paper, we propose an explanation of EAST effects based on a task-set switching account. Specifically, we argue that EAST effects result from difficulties in efficiently switching between two different task sets. Results from two experiments support the assumptions of the task-set switching account: While there were strong EAST effects in task-shift trials, no robust effects were found in task-repetition trials. In Experiment 2, the robustness of this task-shift effect on the EAST was demonstrated: Visual similarity between concept and attribute stimuli did not qualify the task-shift effects. Implications for the interpretation of EAST effects are discussed. PMID- 17341018 TI - Deconfounding the effects of congruency and task difficulty on hemispheric differences in global/local processing. AB - Although it is often assumed that the left and right cerebral hemispheres are specialized for local and global processing, respectively, recent studies show that this difference mainly occurs if the responses to the two levels of a stimulus are conflicting. In the present study we examined whether the favorable effect of response conflicts is caused by the increased task difficulty in this situation. To this end, the response selection for nonconflicting stimuli was complicated by frequently changing the stimulus-response mappings. As a result, the reactions to nonconflicting stimuli were as slow as those to conflicting ones. Nevertheless, hemispheric differences were again restricted to the latter situation. This shows that increased task difficulty can not explain the modulating effect of response conflicts. The results support the alternative hypothesis that different representations are needed for the response selection for nonconflicting and conflicting stimuli, and that the hemispheres differ only with respect to the latter. PMID- 17341019 TI - [Contagious bovine pleuropneumonia--a nearly forgotten disease?]. AB - Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subsp. mycoides small colony type (MmmSC) is a notifiable disease and has to be reported to the World Organisation for Animal Health (Office International des Epizooties, OIE, http://www.oie.int). Despite the fact that the last reported cases in Germany date back to 1926, the risk of introduction through clinically inconspicuous animals from countries where the disease is still endemic is rising. This is due mainly to an increase in international trade of live cattle and the failure to contain CBPP in many parts of Africa and elsewhere. To detect and eliminate this highly contagious infectious disease of the bovine respiratory tract, it is necessary to recognize matching clinical symptoms as soon as possible, as well as to have efficient methods for its detection on hand. In the present paper, we describe clinical manifestations and review state-of-the-art research, as well as currently used detection methods. PMID- 17341020 TI - [Intersexuality in horses]. AB - Intersexuality is a rare congenital anomaly of horses. Diagnosis of intersexuality is difficult because there are usually no specific changes in the reproductive tract visible. During a period of five years, ten patients with reduced fertility or suspected intersexuality respectively were investigated using cytogenetic, molecular genetic, histopathological and endocrinological methods. In one case a 64,XX/63,X0 mosaicism was found. In six cases male pseudohermaphroditism was verified. These patients showed a male karyotype, testes and rudimentary parts of a female reproductive tract were present. One horse was suspected to be a male pseudohermaphrodite but the gonads were not examined. One horse was suspected to be affected by an XX-sex several syndrome and in one case a SRY-negative XY-sex reversal syndrome was most likely. In the case of an XX-sex reversal syndrome, there is a female chromosomal constitution, an uterus and cranial parts of the vagina are present but also testes tissue and possibly an enlarged penis like clitoris. Here an XX-sex reversal syndrome was suspected but not confirmed as it was not possible to examine the gonads and verify tissue from testes. Therefore a pseudohermaphroditismus femininus could not be excluded. In cases of XY-sex reversal syndrome the patients show a male chromosomal constitution, parts of a female reproductive tract but no testes tissue is present. For the horse described here, a deletion of the SRY gene was the most likely cause for the XY-sex reversal syndrome. PMID- 17341021 TI - Glucose tolerance test during abomaso-duodenal electromyography in three cows operated for left displaced abomasum. AB - The objective of the study was to analyze glucose metabolism and abomasal myoelectrical activity during an intravenous glucose tolerance test in cows operated for LDA. Three dairy cows, at the onset of lactation, suffering from left displaced abomasum were selected from the animals presented at the clinic. During surgical therapy, one pair of electrodes was placed in the smooth muscle of the abomasal body, the pars pylorica and the duodenum respectively. The animals were subjected to electromyography on five occasions during hospital admittance (Days 1, 2, 3, 5 and 7 post-operative); their insulin, glucagon, glucose, beta-hydroxybutyrate and NEFA levels were then measured. Two days after surgery, the animals were subjected to an intravenous glucose load (300 g glucose in 30 min) during abomaso-duodenal electromyography. The findings indicate that the three animals had glucose metabolism disorders during hospitalization. The abomaso-duodenal myoelectric activity of Cows 1 and 3 was lower than in Cow 2. During the glucose load, the analysis of hormones and metabolites showed that there were different degrees of reactivity and that myoelectric activity differed in the 3 cows. The results of the study suggest that despite the surgical reposition of the abomasum, disorders of abomasal motility persist in different degrees in cows operated for LDA and could be influenced by glucose administrations. PMID- 17341022 TI - A field study on the efficacy of doramectin against strongyles and its egg reappearance period in horses. AB - The aim of the present study was to determine the efficacy and the so-called "egg reappearance period" (ERP) of doramectin in horses naturally infected with strongyles during a period of 34 weeks. A group of yearlings of 10 animals was treated intramuscularly with doramectin at a dose rate of 0.2 mg/kg bodyweight (BW) at the begin of the grazing season. To obtain comparable data, another group of yearlings (n = 10) was treated orally with ivermectin at a dose rate of 0.2 mg/kg BW. Individual faecal samples were examined for strongyle egg counts per gram of faeces (EPG) in two-week intervals. Twelve weeks later, a second treatment was given in both groups with the respective anthelmintic followed by a third treatment when the group mean egg count reached > or = 200 EPG. The efficacy of doramectin was > or = 96 % and that of ivermectin 100%, based on the mean egg counts two weeks post treatments (wpt). The highest and the lowest extensity of the efficacy (average values) for doramectin were 90% and 41% two and ten wpt, respectively, whereas these values for ivermectin differed from 100% (two wpt) to 24.3% (eight wpt). The ERP was found to be 10 and 8 weeks for doramectin and ivermectin, respectively. PMID- 17341023 TI - Design and X-ray crystal structures of human thrombin with synthetic cyanopeptide analogues. AB - Based on the X-ray crystals of cocrystallized cyanopeptide-trypsin and cyanopeptide-thrombin-com-plexes, a rational drug design succeeded in the establishment of suitable lead structures for the development of new potential inhibitors of thrombin. This report deals with the design and X-ray crystallography data of new synthetic, low-molecular weight cyanopeptide analogues, RA-1008 and RA-1014, complexed with human alpha-thrombin at 1.85 A resolution. The crystal structures of the complexes reveal, by analogy with modeling studies, that the salt bridge of Asp189 to this type of synthetic thrombin inhibitors leads to an almost identically binding into the S1 specificity pocket in comparison to the complex of the natural products, whereas in the overall binding modes the P2-P4 substructures differ from those of the leads. The strongest member of the second series of described thrombin inhibitors, RA-1014, shows in the crystal complex with thrombin a slightly higher affinity towards the enzyme than RA-1008 as confirmed by inhibition tests. This result and other key informations will be helpful to design a more potent series of inhibitors. PMID- 17341024 TI - [Benzo[c][2,7]naphthyridine-5-yl-arylamines-phenol Mannich bases of the amodiaquine-, cycloquine- and pyronaridine-type]. AB - 2,5-Dichloro-4-methyl-benzo[c][2,7]naphthyridine (1) reacted with aromatic amines selectively by substitution at the 5-position to yield the amidines 2. The 4 aminophenol 2c could also be synthesized by cleavage of the ether 2b. The structure of 2c was proved by X-ray crystal analysis. Aminomethylation of 2c yielded the amodiaquine analogue 3. The mono- and bisaminomethylated derivatives 4 and 5 were obtained by reaction of compound 1 with phenol Mannich base hydrochlorides. Compounds 3-5 were tested in vitro for antimalarial activity using chloroquine-sensitive and resistant Plasmodium-falciparum strains. The highest activities were shown by the pyronaridine-type compounds 5a and 5b with IC50 values of approximately 200 nM. PMID- 17341025 TI - Determination of formoterol in rat plasma by liquid chromatography-electrospray ionisation mass spectrometry. AB - A sensitive method for the determination of formoterol in rat plasma is described, using high performance liquid chromatographic separation with tandem mass spectrometry. Samples were purified using liquid-liquid extraction and separated on CAPCELL PAK C18 UG120 (2.0 x 150 mm) with a mobile phase consisting of a mixture of methanol- 50 mM ammonium hydrogen carbonate (1:1 v/v). Detection was performed with a TSQ 7000 mass spectrometer using positive ion electrospray ionisation, monitoring the shift from precursor ions for formoterol at m/z 344.9 to product ions of m/z 121.0. The limit of quantitation of the method was found to be 0.1 ng/ml, when using 0.1 ml plasma. Plasma concentrations of formoterol could be quantified from 0.15 to 7.01 ng/ml, allowing the analysis of samples up to 32 h after a single oral dose of formoterol fumarate (0.25 mg) to rats. PMID- 17341026 TI - Simple and reliable HPLC analysis of fexofenadine hydrochloride in tablets and its application to dissolution studies. AB - A simple RP-HPLC method using a PDA detector was developed and validated for the analysis and dissolution studies of fexofenadine hydrochloride (FEX) in dosage forms. Mobile phase: triethylamine phosphate 1%, pH 3.2: acetonitrile(ACN):methanol (50:30:20), 210 nm detection, C18 Phenomenex& column. The method was validated regarding accuracy/precision (RSD < 1%), linearity (r2 = 0.9999), and robustness. The method was applied to the determination of the drug in commercial tablet preparations and proved to be fast and reliable for quantification and it was also used for the comparison of dissolution profiles of FEX tablets. When we used the factor f2 as a comparison parameter, all the medium didn't present difference in the formulations, but just in the HCI 0.1 M the formulations showed similar results for the parameters f1/f2 andDE allowing to affirm that the two formulations are similar and with the same performance in vivo. PMID- 17341027 TI - RP-HPLC analysis of flucloxacillin in human plasma: validation and application to a bioequivalence study. AB - A RP-HPLC method with rapid sample processing was developed for quantitation of flucloxacillin in human plasma using dicloxacillin as the internal standard. The plasma sample (100 microL) was acidified with glacial acetic acid, and deproteinized by precipitation with acetonitrile. The supernatant was directly injected into the HPLC system. Separation was achieved on an Alltima C18 column (250 mmx4.6 mm I.D., 5 microm), with a mixture of 10 mmol x L(-1) KH2PO4 acetonitrile (64.5:35.5, v/v) as mobile phase. The assay was successfully applied to a randomized, two-period cross-over bioequivalence study in 20 healthy Chinese volunteers following a single oral dose of 250 mg flucloxacillin capsules. A non compartmental method was used for pharmacokinetic analysis. Compared with data in the literature, flucloxacillin was eliminated more slowly in Chinese than in Caucasians. Cmax, AUC(0-t) and AUC(0-infinity) were tested for bioequivalence after log-transformation of data. No significant difference was found. Tmax was analyzed by Wilcoxon's test and no significant difference was obtained (P > 0.05). Based on these statistical inferences, the two formulations were judged to be bioequivalent and, thus, can be prescribed interchangeably. PMID- 17341028 TI - Photoreactivity of biologically active compounds. XVIII. Photostability of ofloxacin in the solid state and in a tablet formulation. AB - The photostability of ofloxacin in the solid state has been investigated. The change in colour of uncoated and film coated ofloxacin tablets and compressed ofloxacin was studied as a function of irradiance level and total exposure energy. The degradation of ofloxacin in the various preparations was quantified by HPLC and the antimicrobial activity was determined for selected tablets. The structure of two main degradation products from ofloxacin in the solid state has been postulated from LC-MS analysis. Both products have an absorption cut-off below 400 nm and cannot explain the observed change in tablet colour. There was no apparent relationship between the change in colour and the loss of active substance or antibacterial activity for the preparations investigated. The change in colour was easily detectable at rather low exposure levels. Apparently, there was a difference in light sensitivity between the two film-coated tablet batches investigated. The results obtained were partly dependent on the conditions within the radiation chamber (e.g., exposure time and irradiance level), which emphasizes the importance of testing the samples under various conditions unless the results are unequivocal. The tablets were sensitive to visible light although ofloxacin only has a neglectible absorption above 400 nm. The film coated ofloxacin tablets did, however, absorb above 400 nm with a cut-off at approximately 520 nm. A change in tablet coating to include a component that filters visible light in addition to UV radiation might provide a solution to the discolouration problem and prevent batch to batch variations with respect to light sensitivity. PMID- 17341029 TI - Kinetics of decomposition of rabeprazole sodium in aqueous solutions determined by high performance liquid chromatography. AB - The kinetics of decomposition of rabeprazole sodium in aqueous solutions at elevated temperatures has been investigated by high performance liquid chromatography. The reaction is found to follow first-order kinetics and the rate constant for the degradation at 25 degrees C is estimated by extrapolation. The breakdown of rabeprazole sodium is shown to be water and hydrogen ion catalysed and the effects of ionic strength and buffer concentrations to such rate studies are discussed. PMID- 17341030 TI - The determination of in vitro pingyangmycin hydrochloride plasma protein binding by microdialysis. AB - Microdialysis sampling was used to study the binding of pingyangmycin hydrochloride (PYM) to plasma proteins in canis familiaris blood. In vitro plasma protein binding fractions were evaluated in a series of PYM concentration. The results showed decreased protein binding with increased concentration. The data was analyzed using the Scatchard analysis and Klotz plot. The results showed that the Scatchard plot and Klotz plot were linear with good correlation coefficient, indicating a good agreement of the experimental data to the theoretical equation. PMID- 17341031 TI - Preparation and in vitro evaluation of ethyl cellulose microspheres containing stavudine by the double emulsion method. AB - The aim of this study was to formulate and evaluate microspheres of stavudine by water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion method using ethyl cellulose and ethyl cellulose in combination with polyvinyl pyrrolidone. A mixed solvent system consisting of acetonitrile and dichloromethane in an 1: 1 ratio and light liquid paraffin was chosen as primary and secondary oil phase, respectively. Span 80 was used as surfactant for stabilizing the secondary oil phase. The influence of formulation factors like stirring speed, surfactant concentration on particle size and polymer:drug ratio and combination of polymers on drug release characteristics of the microspheres was investigated. The prepared microspheres characterized by micrometric properties, drug loading, Fourier transform infrared spectroscopy, X-ray powder difractometry and scanning electron microscopy. The prepared microspheres were white, free flowing and spherical in shape, stable in nature, with 41-65% of drug entrapment efficiency. The best-fit release kinetics was achieved with Higuchi plot followed by first order and zero order. The release of stavudine was influenced by the drug to polymer ratio, particle size and polymer combination. PMID- 17341032 TI - Formulation and evaluation of ethyl cellulose microspheres prepared by the multiple emulsion technique. AB - The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of metformin hydrochloride using ethyl cellulose as the retardant material with high entrapment efficiency and extended release. Microspheres were prepared by the double emulsion solvent diffusion method. A mixed solvent system consisting of acetonitrile and dichloromethane in 1:1 ratio and light liquid paraffin were chosen as the primary and secondary oil phases, respectively. Span 80 was used as the surfactant for stabilizing the secondary oil phase. The prepared microspheres were characterized by drug loading, optical microscopy and scanning electron microscopy (SEM). The in vitro release studies were performed in a series of buffer solutions with variable pH. The drug loaded microspheres showed 55-85% of entrapment and the release was extended for up to 12 h. SEM studies revealed that the microspheres were spherical and porous in nature. Data obtained from in vitro release studies were fitted to various kinetic models and high correlation was obtained with the Higuchi model. The drug release was found to be diffusion controlled. Oral administration of the microspheres to the albino mice provided decreased plasma glucose for more than 10 h. PMID- 17341033 TI - Preparation and evaluation of paclitaxel-containing liposomes. AB - Paclitaxel, an antitumoral drug, is poorly soluble in aqueous media. Therefore, in a commercialised formulation (Taxol), paclitaxel (30 mg active compound) is dissolved in polyethoxylated castor oil (Cremophor EL) and ethanol. After dilution of Taxol in aqueous media paclitaxel tends to precipitate. Several side effects, attributed to the surfactant Cremophor EL, occur, e.g. bronchospasm, hypotension, neuro- and nephrotoxicity, and anaphylactic reactions. To eliminate these side effects, the solubility of paclitaxel was enhanced using liposomes instead of Cremophor EL. The amount of entrapped paclitaxel in crystal-free liposomes was 0.5 mg/ml liposome suspension, i.e. almost 85 times the native solubility. Thus, 30 mg paclitaxel had to be dissolved in 60 ml liposome suspension, of either multi-lamellar vesicles (MLV's) or of small unilamellar vesicles (SUV's) with 5% sucrose as cryoprotector. No precipitation was observed after dilution of the MLV-formulation with (physiological) water or with 5% aqueous dextrose solution, which proves their suitability for administration with perfusions. The chemical stability of paclitaxel in the prepared MLV's stored at 4 degrees C was demonstrated during a period of 5 months. The chemical degradation to conjugated dienes and hydroperoxides, two oxidative degradation products of EPC, was negligible (less than 1%). PMID- 17341034 TI - Deformable liposomes and ethosomes as carriers for skin delivery of ketotifen. AB - Deformable liposomes and ethosomes were investigated as carriers for skin delivery of ketotifen (KT) in terms of vesicle size, entrapment efficiency, stability, in vitro permeation and skin deposition properties. Phosphatidylcholine (PC) from soybean lecithin was used in the preparation of all vesicles. Sodium cholate, sodium deoxycholate and Tween 80 were investigated as edge activators in preparation of KT deformable liposomes. KT ethosomes were prepared in two PC concentrations, 2% and 4.25% w/v, in 30% v/v ethanol. KT deformable liposomes showed improved entrapment efficiency over KT ethosomes. KT deformable liposomes with Tween 80 as an edge activator were more stable upon storage at 5 +/- 1 degree C than those prepared using sodium cholate or sodium deoxycholate and were more stable than KT ethosomes. In vitro permeation and skin deposition studies employed only deformable liposomes with Tween 80 as an edge activator and ethosomes with 4.25% w/v PC concentration. Both of them improved skin delivery of KT over controls and over traditional liposomes, with greater improvement of KT skin deposition than KT skin permeation, hence are more useful for dermal than for transdermal delivery of KT. PMID- 17341035 TI - Development and in vitro evaluation of topically applied cinnamic acid formulations. AB - The aim of this study was to formulate microcapsulated cinnamic acid (CN) formulations in w/o and o/w emulsions and to compare their release profiles with w/o, o/w and w/o/w emulsions without microcapsules through cellulose acetate, cellulose nitrate membranes and excised rat skin. The experimental design approach was used for understanding the influence of different formulation factors on release characteristics and to optimise most accurate formulating parameters. The data obtained in this study were subjected to statistical analysis by a repeated measures ANOVA, following Bonferroni multiple comparisons test. A significantly different release was observed due to the core:wall ratio of microcapsules. Emulsions containing microcapsules with 2:1 core:wall ratio were found to be ideal according to the factorial design, dissolution and diffusion studies. The type of emulsion was found to be a very important factor affecting the release profile of CN. The results described in this study indicate that microencapsulation of CN in w/o emulsion could be suggested as an effective carrier for CN to achieve sustained release and to protect the drug. Moreover, w/o/w emulsions were also useful carriers for prolonged release by encapsulating the substances in their internal aqueous phase and they also protect drugs and their preparation and application are easy. By the way, in the case of o/w emulsion any significant difference was observed. The type of the membrane also affected release. According to the release results, rat skin was found to be significantly different from the synthetic membranes. PMID- 17341036 TI - Design and in vitro testing of a floatable gastroretentive tablet of metformin hydrochloride. AB - Metformin hydrochloride, which is better absorbed in the upper intestine, was formulated as a floating (buoyant) matrix tablet using a gas generating agent (sodium bicarbonate) and a gel forming hydrophilic polymer (hydroxypropyl methylcellulose). The formulation was optimized on the basis of floating ability and in vitro drug release. The resulting formulation produced robust tablets with optimum hardness, consistent weight uniformity and low tablet friability. All tablets but one exhibited satisfactory (gradual and near complete) drug release and buoyancy. In vitro drug release tests of these tablets indicated controlled sustained release of metformin hydrochloride and 96-99% released at the end of 8 h. Two formulations of fabricated tablets containing metformin hydrochloride (500 mg), sodium bicarbonate (75 mg), hydroxypropyl methylcellulose-K 4M (170-180 mg), citric acid (between 15 and 20 mg) and polyvinyl pyrrolidone K90 (32-40 mg) with hardness between 6.8 to 7.5 kg/cm2 showed a floating time of more than 8 h and promising drug release results. The release followed the Higuchi kinetic model, indicating diffusion dominated drug release. PMID- 17341037 TI - Baicalein, a flavonoid extracted from a methanolic extract of Oroxylum indicum inhibits proliferation of a cancer cell line in vitro via induction of apoptosis. AB - A methanolic extract of the fruits of Oroxylum indicum, which is widely used in traditional Chinese herbal medicine for its anti-inflammatory, anti-pyretic and anti-hypersensitivity effects, inhibited in vitro proliferation of HL-60 cells. The flavonoid baicalein was found as an active component in the extract. Analysis of freeze-dried fruits of the plant indicated that this component comprised about 4% of the material by dry weight. In this study, we investigated the in vitro effects of baicalein on the viability and induction of apoptosis in the HL-60 cell line. The cell viability after treating with baicalein for 24 h was quantified by counting viable cells using trypan blue staining. The results showed that baicalein caused a 50% inhibition of HL-60 cells at concentrations of 25-30 microM. The inhibition of proliferation of HL-60 cells due to 36-48 h exposure to 10 or 20 microM baicalein was associated with the accumulation of cells at S or G2M phases. However, proliferation inhibition at a higher dose may be associated with induction by apoptosis, as evidenced by the typical nuclear fragmentation using DNA fragmentation assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The results indicate that baicalein has anti-tumor effects on human cancer cells, and Oroxylum indicum extract could be used in supplementary cancer therapy. PMID- 17341038 TI - Bebrycoside, a new steroidal glycoside from the Chinese gorgonian coral Bebryce indica. AB - A new steroidal glycoside, bebrycoside (1), was isolated from the South China Sea gorgonian coral Bebryce indica. The structure of 1 was established by extensive spectroscopic analysis, including 1D and 2D NMR data. This was the first time that the steroidal glycoside was isolated from the genus of Bebryce. PMID- 17341039 TI - Effect of acceptor phosphate buffer pH value on indomethacin release. AB - This contribution investigated in vitro release of the antirheumatic drug indomethacin in relation to phosphate buffer pH in the acceptor part of the permeation apparatus. Drug release was studied from a hydrogel containing 3% of hydroxyethyl cellulose and from a cream. UV-spectroscopic evaluations were done after the preparation of the study drugs. Indomethacin release depends on the pH of the acceptor phosphate buffer, the higher pH value the better release. PMID- 17341040 TI - Prediction of plasma protein binding of cephalosporins using an artificial neural network. AB - An artificial neural network model is developed to predict the fraction of cephalosporins bound to plasma proteins (f(b)) from their molecular structural parameters. These molecular structural parameters are the molecular weight (MW), the surface area occupied by oxygen and nitrogen atoms (S(O),N), and the surface area occupied by hydrogen atoms attached to oxygen or nitrogen atoms (S(H)). For a training set of 20 cephalosporins and a test set of 3 cephalosporins, root mean squared errors (RMSE) between experimental fb values and calculated/predicted fb values are 0.036 and 0.045, respectively. PMID- 17341041 TI - Similar effects of clozapine and olanzapine on ethanol-induced ascorbic acid release in the prefrontal cortex of freely moving mice. AB - Previous studies have shown that acute systemic administration of ethanol induced ascorbic acid (AA) release in mouse striatum and prefrontal cortex. Clozapine and olanzapine showed similar effects on ethanol-induced AA release in mouse striatum. However, their effects on ethanol-induced AA release in mouse prefrontal cortex have not been reported. Thus, their effects on this neurochemical event were further investigated in the present study. The results showed that ethanol (4.0 gkg i.p.) significantly stimulated AA release in the prefrontal cortex by about 200 of baseline in mice. Clozapine and olanzapine, at the dose of 1.0 mgkg s.c., had no effect on basal AA or ethanol-induced AA release. However, both drugs, at the dose of 10 mgkg s.c., significantly inhibited ethanol-induced AA release. The present study demonstrated for the first time that similar actions were exhibited by clozapine and olanzapine for the regulation of ethanol-induced AA release in the mouse prefrontal cortex. PMID- 17341042 TI - Psychological factors in spinal cord stimulation therapy: brief review and discussion. AB - Since its introduction in 1967 by Shealy and colleagues, spinal cord stimulation (SCS) therapy has become an accepted approach to the treatment of certain types of chronic pain. Significant advances have been made in surgical technique, hardware technology, and the variety of disorders for which SCS has proven to be potentially beneficial. Despite these advancements, 25 to 50% of patients in whom a preimplantation trial screening yields successful results report loss of analgesia within 12 to 24 months of implantation, even in the presence of a functioning device. Psychological factors may play an important role in understanding this observation and improving the outcomes. In this article the author briefly reviews some of the data on psychological factors potentially involved in SCS. Research on patients with low-back and extremity pain was more heavily relied on because this is the population for which the most data exist. The discussion is divided into four sections: 1) role of psychological factors; 2) psychological screening and assessment; 3) patient selection and psychological screening; and 4) psychological variables and outcomes. To date, the data remain speculative. Although few definitive conclusions can be drawn, the cumulative existing experience does lend itself to some reasonable recommendations. As with all therapies for chronic pain, invasive or noninvasive, the criteria for success and an acceptable level of failure need to be established, but remain elusive. The emphasis herein is to try to take what works and make it work better. PMID- 17341043 TI - Selective enhancement of cellular oxidative stress by chloroquine: implications for the treatment of glioblastoma multiforme. AB - Chloroquine is used in the treatment of malaria, a disease caused by infection with the parasite Plasmodium. Although chloroquine appears to possess diverse pharmacological activity, its plasmodicidal activity results from augmentation of parasite oxidative stress. Chloroquine also appears to augment oxidative stress in metabolically active mammalian cells, including human astroglial cells. The authors propose that chloroquine may augment oxidative stress induced by radiotherapy in the treatment of glioblastoma multiforme, enhancing therapeutic efficacy. Such an effect would be consistent with the known pharmacological effects of chloroquine observed in Plasmodium. Other selective redox agents, such as tempol and artemisinin, should be investigated clinically for therapeutic benefit when coadministered with combined radio- and chemotherapy for cancer. PMID- 17341044 TI - Spinal vascular malformations: an historical perspective. AB - In this historical perspective, the author identifies three epochs in the development of the concepts and treatment of spinal vascular lesions: 1) early observations (1860s-1912), with the lesions during this time period recognized only at autopsy; 2) the "middle ages" (1912-1960), with surgical intervention sporadic and yielding dismal results; and 3) the modern era (beginning in the 1960s), coincident with parallel dramatic advances in radiology, microsurgical instrumentation, and anesthesiology. These advances resulted in a better understanding of the pathophysiological aspects and angioarchitecture of the lesions. Whereas the nomenclature of the lesions in the past was confusing, a new understanding of these diseases that has emerged during the modern era has permitted refinement of the classification of the lesions as distinct biological entities. Modern diagnostic imaging has enabled identification of patients who may benefit from surgical or embolic occlusion, and treatment has become rationally based. Future progress in the management of spinal vascular lesions may be anticipated, with improvement in noninvasive imaging for early detection of suspected abnormalities. Furthermore, advances in spinal cord neuroprotection may expand the range of future options for surgical or embolic intervention. PMID- 17341045 TI - Is clear cell sarcoma a malignant form of psammomatous melanotic schwannoma? Case report. AB - The authors present a case of clear cell sarcoma (CCS) in which the tumor originated in the S-1 nerve root and had been previously diagnosed as psammomatous melanotic schwannoma (PMS). This is the third case of a spinal nerve root origin for CCS reported in the English-language literature. The similar histogenesis of CCS and malignant melanoma supports the hypothesis that biological agents or immunotherapy are potentially important areas of investigation. The patient underwent S1-3 laminectomy and gross-total resection of the mass lesion. The border of the resection was extended 1 cm distal to the tumor margin. The postoperative period was uneventful. The new histopathological diagnosis was CCS (malignant melanoma of soft tissue). Despite total resection, the patient returned with disseminated disease at the 18-month follow-up visit. His follow-up magnetic resonance image of the lumbar spine revealed sacral L5-S3 involvement of the vertebral bodies along with disseminated cauda equina seeding. A CCS originating from peripheral nerves is quite rare. The histopathological and immunohistochemical appearance of CCSs resembles those of PMSs. Surgery should be the first choice of treatment. PMID- 17341046 TI - Mechanisms of spinal cord stimulation in ischemia. AB - OBJECT: The goal of this study was to assess the duration of neuroprotection after SCS. Nearly 40 years after the first description of spinal cord stimulation (SCS), the mechanisms underlying its physiological effects remain unclear. It is known that SCS affects activity in the nervous system on a broad scale. Local neurohumoral changes within the dorsal horn of the spinal cord have been described, as have changes in cortical activation in a number of brain regions. Spinal cord stimulation has even been found to have profound effects on sympathetic vascular tone, a discovery that has led to its use in ameliorating blood flow in the limbs, heart, and brain. METHODS: In an effort to delineate the limits of neuroprotection offered by SCS, the authors have studied its use in an experimental model of permanent middle cerebral artery (MCA) occlusion in rats. The investigators applied SCS in a delayed fashion 3, 6, or 9 hours after MCA occlusion. The results are reported and mechanisms underlying the physiological effects of SCS are reviewed, with particular attention being paid to the effect of SCS on cerebral blood flow in the setting of cerebral ischemia. CONCLUSIONS: The authors found that SCS applied as late as 6 hours postischemia significantly reduces stroke volumes, whereas SCS applied 9 hours after ischemia fails to reduce stroke injury. PMID- 17341047 TI - Spinal cord stimulation: indications and outcomes. AB - Spinal cord stimulation (SCS) is the most commonly used implantable neurostimulation modality for management of pain syndromes. In this paper the authors describe the current indications for SCS and its efficacy in the treatment of those diseases. Specifically, the literature on patient selection and outcomes after SCS for failed-back surgery syndrome (FBSS), refractory angina pectoris, peripheral vascular disease, and complex regional pain syndrome (CRPS) Type I was reviewed. Effective pain relief was obtained in 60 to 80% of patients with FBSS and CRPS Type I. Furthermore, these patients had significant improvements in quality of life (QOL) and a significantly greater chance of returning to work than patients who did not undergo SCS. The use of SCS in patients with inoperable angina (that is, refractory angina pectoris) resulted in significant decreases in chest pain and hospital admissions as well as increased exercise duration, with less morbidity than with open procedures that were performed for pain control only. Patients with inoperable PVD also demonstrated significant improvements in pain relief, QOL, and limb mobility. Reported complications were mostly related to hardware and were relatively minor. Review of randomized controlled studies supports the use of SCS as an effective treatment modality for pain associated with FBSS, refractory angina pectoris, peripheral vascular disease, and CRPS Type I. PMID- 17341048 TI - Spinal nerve root stimulation. AB - Spinal nerve root stimulation is a recently developed form of neuromodulation used for the treatment of chronic pain conditions. Unlike spinal cord stimulation, in which electrical impulses are directed at the dorsal columns, spinal nerve root stimulation guides electrical current directly to one or more nerve roots. There are a variety of techniques by which this can be accomplished, yet no consistent terminology to describe these variations exists. In this review, the authors group the various techniques according to anatomical approach, define each category, describe and illustrate each of the techniques, review the available reports on their uses, and discuss the advantages and disadvantages of each one. PMID- 17341049 TI - Trigeminal and occipital peripheral nerve stimulation for craniofacial pain: a single-institution experience and review of the literature. AB - OBJECT: Treatment of chronic neuropathic pain in the region of the head and face presents a challenge for pain specialists; patients who do not respond to conventional treatment modalities usually continue to suffer from pain due to the lack of reliable medical and surgical approaches. Peripheral nerve stimulation (PNS) has been used to treat neuropathic pain for many decades, but only recently has it been applied systematically to the craniofacial region. To advance the study of this treatment option, the authors present their initial experience with this approach, summarize published data on the use of PNS in treatment of craniofacial pain, and discuss some technical details of the craniofacial PNS procedure. METHODS: A review of prospectively collected data in 30 patients who underwent PNS surgery for craniofacial pain was performed. The pain location, duration, cause, and previous treatments were analyzed, along with the surgical details, initial and long-term results, complications, and repeated operations. Stimulated nerves in this group included supraorbital (seven patients), infraorbital (six), and occipital (21); in 19 patients more than one nerve was stimulated. Twenty-two patients proceeded with implantation of a permanent system after the trial. Of these, at the time of the latest evaluation (mean follow-up duration 35 months), in two patients the devices had been removed because of pain improvement over time, in three the devices were removed due to loss of effectiveness (two cases) or late infection (one), and the rest are enjoying either complete (15 patients) or partial (two patients) pain relief. Three patients underwent repeated operation due to lead erosion, infection, or migration. CONCLUSIONS: Peripheral nerve stimulation appears to be a safe and effective approach in the treatment of craniofacial neuropathic pain. The growing body of literature supports a wider acceptance of this approach in the field of pain surgery. PMID- 17341050 TI - Motor cortex stimulation and neuropathic facial pain. AB - Trigeminal neuropathic pain is a syndrome of severe, constant facial pain related to disease of or injury to the trigeminal nerve or ganglion. Causes of this type of pain can include injury from sinus or dental surgery, skull and/or facial trauma, or intentional destruction for therapeutic reasons (deafferentation) as well as intrinsic pathological conditions in any part of the trigeminal system. Motor cortex stimulation (MCS) is a relatively new technique that has shown some promise in the treatment of trigeminal neuropathic pain. This technique has the potential to revolutionize the treatment of chronic pain. The authors present a review of the literature, focusing on surgical technique, device programming, safety, and efficacy, and suggest some initial guidelines for standardization of these aspects. It is important to evaluate MCS critically in a prospective, controlled fashion. PMID- 17341051 TI - Motor cortex stimulation for intractable pain. AB - Effective management of neuropathic pain is one of the more challenging endeavors for even the most experienced and skilled pain specialist. Pharmacological therapy is frequently ineffective and/or poorly tolerated, especially in elderly patients. Many if not most surgical procedures have yielded limited success in the treatment of these pain conditions. Motor cortex stimulation (MCS) has emerged as a promising technique for the management of pain in patients with difficult neuropathic and central pain conditions. Although MCS has proven most successful for patients with trigeminal neuropathic/deafferentation pain and central poststroke pain, other conditions are now emerging as potential targets for this therapy. Based on previous as well as ongoing work, it would appear that the future of MCS is indeed bright. Hopefully, as work continues in this area, investigators will be able to develop a better understanding of the mechanisms underlying this modality and be able to further refine the technique of MCS. It is also possible that with the use of noninvasive tools such as transcranial magnetic stimulation, practitioners will be able to predict with accuracy which patients are likely to respond favorably to MCS. PMID- 17341052 TI - Deep brain stimulation for the treatment of various chronic pain syndromes. AB - OBJECT: Electrical intracerebral stimulation (also referred to as deep brain stimulation [DBS]) is a tool for the treatment of chronic pain states that do not respond to less invasive or conservative treatment options. Careful patient selection, accurate target localization, and identification with intraoperative neurophysiological techniques and blinded test evaluation are the key requirements for success and good long-term results. The authors present their experience with DBS for the treatment of various chronic pain syndromes. METHODS: In this study 56 patients with different forms of neuropathic and mixed nociceptive/neuropathic pain syndromes were treated with DBS according to a rigorous protocol. The postoperative follow-up duration ranged from 1 to 8 years, with a mean of 3.5 years. Electrodes were implanted in the somatosensory thalamus and the periventricular gray region. Before implantation of the stimulation device, a double-blinded evaluation was carefully performed to test the effect of each electrode on its own as well as combined stimulation with different parameter settings. The best long-term results were attained in patients with chronic low-back and leg pain, for example, in so-called failed-back surgery syndrome. Patients with neuropathic pain of peripheral origin (such as complex regional pain syndrome Type II) also responded well to DBS. Disappointing results were documented in patients with central pain syndromes, such as pain due to spinal cord injury and poststroke pain. Possible reasons for the therapeutic failures are discussed; these include central reorganization and neuroplastic changes of the pain-transmitting pathways and pain modulation centers after brain and spinal cord lesions. CONCLUSIONS: The authors found that, in carefully selected patients with chronic pain syndromes, DBS can be helpful and can add to the quality of life. PMID- 17341053 TI - Silicate-substituted calcium phosphate as a bone void filler after kyphoplasty in a young patient with multiple compression fractures due to osteogenesis imperfecta variant: case report. AB - Kyphoplasty can be used to treat compression fractures resulting from a variety of causes. The use of polymethyl methacrylate (PMMA) in conjunction with kyphoplasty has many risks and potential complications, however, particularly in the younger patient population. Silicate-substituted calcium phosphate (Actifuse Synthetic Bone Graft; Apatech, Ltd.) is an alternative to PMMA that provides immediate pain relief and the ability to heal and incorporate within the vertebral body. PMID- 17341054 TI - Fluorescent nanoparticles for multiplexed bacteria monitoring. AB - Rapid, sensitive, and selective detection of pathogenic bacteria is extremely important for proper containment, diagnosis, and treatment of diseases like foodborne illness, sepsis, and bioterrorism. Most current bacterial detection methods are time-consuming and laborious and can detect only one bacterial pathogen at a time. We have developed a method for sensitive, multiplexed monitoring of bacterial pathogens within 30 min using multicolored FRET (fluorescence resonance energy transfer) silica NPs (nanoparticles). By varying the ratio of three tandem dyes coencapsulated into the NPs, we have synthesized NPs that emit unique colors upon excitation with a single wavelength. When these NPs were conjugated to monoclonal antibodies specific for the pathogenic bacteria species Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus, and then incubated with small concentrations of the bacteria, simultaneous and sensitive detection of the multiple bacterial targets was achieved. PMID- 17341055 TI - Quantitative hydrogen analysis of zircaloy-4 using low-pressure laser plasma technique. AB - It is found in this work that variation of laser power density in low-pressure plasma spectrochemical analysis of hydrogen affects sensitively the hydrogen emission intensity from the unwanted and yet ubiquitous presence of ambient water. A special experimental setup has been devised to allow the simple condition of focusing/defocusing the laser beam on the sample surface. When applied to zircaloy-4 samples prepared with various hydrogen impurity concentrations using low-pressure helium surrounding gas, good-quality hydrogen emission lines of very high signal to background ratios were obtained with high reproducibility under weakly focused or largely defocused laser irradiation. These measurements resulted in a linear calibration line with nonzero intercept representing the residual contribution from the recalcitrant water molecules. It was further shown that this can be evaluated and taken into account by means of the measured intensity ratio between the oxygen and zirconium emission lines. We have demonstrated the applicability of this experimental approach for quantitative determination of hydrogen impurity concentrations in the samples considered. PMID- 17341056 TI - Direct immobilization of protein g variants with various numbers of cysteine residues on a gold surface. AB - Protein G is an antibody binding protein, which specifically targets the Fc region of an antibody. It therefore has been widely used to immobilize different types of antibodies in numerous immunoassays. Here, we have engineered Streptococcus protein G to contain various numbers of cysteine residues at the N terminus and therefore to form well-oriented protein G films on bare gold. SPR and SPR imaging analyses indicated that a gold surface treated with cysteine tagged protein G possesses a superior antibody binding ability compared to one treated with tag-free protein G. AFM images indicated a higher surface coverage by antibody binding on the cysteine-tagged protein G surface than the intact protein G surface. The proper orientation of cysteine-tagged protein G on a gold surface also afforded better orientation of immobilized antibodies, resulting in enhanced antigen detection. Moreover, the protein G surfaces maintained their high antibody binding ability during multiple rounds of antibody interaction tests. The cysteine-tagged protein G constructed in this study can be a valuable link for oriented antibody immobilization in a variety of immunosensors. PMID- 17341058 TI - Detecting aerosol particles on surfaces. PMID- 17341057 TI - Probing heterogeneous electron transfer at an unbiased conductor by scanning electrochemical microscopy in the feedback mode. AB - The theory of the feedback mode of scanning electrochemical microscopy is extended for probing heterogeneous electron transfer at an unbiased conductor. A steady-state SECM diffusion problem with a pair of disk ultramicroelectrodes as a tip and a substrate is solved numerically. The potential of the unbiased substrate is such that the net current flow across the substrate/solution interface is zero. For a reversible substrate reaction, the potential and the corresponding tip current depend on SECM geometries with respective to the tip radius including not only the tip-substrate distance and the substrate radius but also the thickness of the insulating sheath surrounding the tip. A larger feedback current is obtained using a probe with a thinner insulating sheath, enabling identification of a smaller unbiased substrate with a radius that is approximately as small as the tip radius. An intrinsically slow reaction at an unbiased substrate as driven by a SECM probe can be quasi-reversible. The standard rate constant of the substrate reaction can be determined from the feedback tip current when the SECM geometries are known. The numerical simulations are extended to an SECM line scan above an unbiased substrate to demonstrate a "dip" in the steady-state tip current above the substrate center. The theoretical predictions are confirmed experimentally for reversible and quasi reversible reactions at an unbiased disk substrate using disk probes with different tip radii and outer radii. PMID- 17341059 TI - 1,4-benzodiazepines as inhibitors of respiratory syncytial virus. The identification of a clinical candidate. AB - Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as representing a serious threat to patient groups with poorly functioning or immature immune systems. Racemic 1,4-benzodiazepines show potent anti-RSV activity in vitro. Anti-RSV evaluation of 3-position R- and S-benzodiazepine enantiomers and subsequent optimization of this series resulted in selection of a clinical candidate. Antiviral activity was found to reside mainly in the S enantiomer, and the R-enantiomers were consistently less active against RSV. Analogues of 1,4-(S)-benzodiazepine were synthesized as part of the lead optimization program at Arrow and tested in the XTT assay. From this exercise, (S)-1-(2-fluorophenyl)-3-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]-diazepin-3 yl)-urea, 17b (RSV-604) was identified as a clinical candidate, exhibiting potent anti-RSV activity in the XTT assay, which was confirmed in secondary assays. Compound 17b also possessed a good pharmacokinetic profile and has now progressed into the clinic. PMID- 17341060 TI - Probing the anticancer activity of nucleoside analogues: a QSAR model approach using an internally consistent training set. AB - The cancer research community has begun to address the in silico modeling approaches, such as quantitative structure-activity relationships (QSAR), as an important alternative tool for screening potential anticancer drugs. With the compilation of a large dataset of nucleosides synthesized in our laboratories, or elsewhere, and tested in a single cytotoxic assay under the same experimental conditions, we recognized a unique opportunity to attempt to build predictive QSAR models. Here, we report a systematic evaluation of classification models to probe anticancer activity, based on linear discriminant analysis along with 2D molecular descriptors. This strategy afforded a final QSAR model with very good overall accuracy and predictability on external data. Finally, we search for similarities between the natural nucleosides, present in RNA/DNA, and the active nucleosides well-predicted by the model. The structural information then gathered and the QSAR model per se shall aid in the future design of novel potent anticancer nucleosides. PMID- 17341061 TI - Structural and functional basis of cyclooxygenase inhibition. PMID- 17341062 TI - Nonprenylated rotenoids, a new class of potent breast cancer resistance protein inhibitors. AB - Two rotenoids isolated from Boerhaavia diffusa (Nyctaginaceae), boeravinones G (1) and H (2), have been found to potently inhibit the drug efflux activity of breast cancer resistance protein (BCRP/ABCG2), a multidrug transporter responsible for cancer cell resistance to chemotherapy. The isolation of nine additional rotenoid derivatives (3-11), including the new boeravinones I (10) and J (11), from the extract of B. diffusa roots allowed us to establish structure activity relationships toward inhibition of BCRP-mediated drug transport activity. The results show the positive roles of a methoxy group at position 6 of ring B and the absence of a substituent at position 10, and the requirement for a 6a/12a double bond between rings B and C. In contrast, both contraction of ring B, to give a coumaronochromone (11), and tetrasubstitution of ring D appeared to be detrimental for the inhibitory potency. The present study provides the first data on the BCRP-inhibiting activity of rotenoid derivatives, indicating boeravinones as a new class of interesting BCRP inhibitors. PMID- 17341063 TI - Complexation of UVI with 1-hydroxyethane-1,1-diphosphonic acid in acidic to basic solutions. AB - Complexation of UVI with 1-hydroxyethane-1,1-diphosphonic acid (HEDPA) in acidic to basic solutions has been studied with multiple techniques. A number of 1:1 (UO2H3L), 1:2 (UO2HjL2 where j = +4, +3, +2, +1, 0, and -1), and 2:2 [(UO2)2HjL2 where j = +1, 0, and -1] complexes form, but the 1:2 complexes are the major species in a wide pH range. Thermodynamic parameters (formation constants and enthalpy and entropy of complexation) were determined by potentiometry and calorimetry. Data indicate that the complexation of UVI with HEDPA is exothermic, favored by the enthalpy of complexation. This is in contrast to the complexation of UVI with dicarboxylic acids in which the enthalpy term usually is unfavorable. Results from electrospray ionization mass spectrometry and 31P NMR have confirmed the presence of 1:1, 1:2, and 2:2 UVIHEDPA complexes. PMID- 17341064 TI - Determination of equilibrium constants and computational interaction energies for adducts of [Rh2(RCO2)(4-n)(PC)n] (n = 0-2) with Lewis bases. AB - Properties of dirhodium catalysts with cyclometalated aryl phosphine ligands have been studied. We report here the study of the acid-base reaction of Rh2(RCO2)2(PC)2(H2O)2 catalysts (PC = cyclometalated aryl phosphine) with different Lewis bases. The determination of the equilibrium constants of these reactions can be used to study to which extent the properties of the axial coordination site of the catalyst, considered the active site, are affected by modification of the metalated phosphines, the carboxylate ligands, or the incoming axial ligand. The trends in the computational density functional theory interaction energies show good agreement with the major trends in the equilibrium constants, thus enabling a further study of the influence of the modification of the ligand core. PMID- 17341065 TI - Self-assembly of a high-nuclearity chloride-centered copper(II) cluster. Structure and magnetic properties of [Au(PPh3)2][trans-Cu6(micro-OH)6[micro-(3,5 CF3)2pz]6Cl]. AB - A chloride-centered hexanuclear copper(II) pyrazolate [Au(PPh3)2][trans-Cu6(micro OH)6[micro-(3,5-CF3)2pz]6Cl] is isolated from the reaction of the trinuclear copper(I) pyrazolate [Cu3[micro-(CF3)2pz]3] with PPh3AuCl and Ph3P in moist air. The six copper atoms are bridged by pyrazolate and hydroxyl ligands, above and below the copper plane. The chloride anion exists at the center of the planar cavity formed by the copper atoms with Cu-Cl distances of 3.02-3.13 A. The magnetic susceptibility measurements show a strong antiferromagnetic coupling between the copper centers with an estimated exchange constant of J approximately 650 cm-1. PMID- 17341066 TI - Why [(eta5-C5Me(n)H5-n)2Ti]2(micro2,eta2,eta2-N2) can not add a H2 molecule to the side-on-coordinated N2 while its Zr and Hf analogues can? insights from computational studies. AB - The potential energy surface of the reaction [(eta5-C5MenH5 n)2M]2(micro2,eta2,eta2-N2) + H2 --> [(eta5-C5MenH5-n)2M][(eta5-C5MenH5 n)2MH](micro2,eta2,eta2-NNH) at low-lying singlet and triplet electronic states of the reactants was investigated using density functional methods, for n = 0 and 4, and M = Ti, Zr, and Hf. Ground electronic states of the Ti complexes are found to be triplet states, while that for the corresponding Zr and Hf complexes are singlet states. In their singlet state, all these complexes satisfy known necessary conditions (they have a side-on-coordinated N2 molecule and appropriate frontier orbitals) for successful addition of an H2 molecule to the coordinated N2, and consequently, add of an H2 molecule with a reasonable energy barrier. Hf complexes show slightly higher reactivity than corresponding Zr complexes, and in turn, both are more reactive than their singlet-state Ti counterparts. The calculated trend in reactivity of Zr and Hf complexes is consistent with the latest experimental data (see refs 13 and 16). However, Ti complexes have the ground triplet state that lacks in appropriate frontier orbitals. As a result, H2 addition to the Ti complexes at their triplet ground states requires a larger activation barrier than the singlet state and is endothermic (lacks of driven force for reaction). On the basis of these results, we predict that the [(eta5 C5Me4H)2M]2(micro2,eta2,eta2-N2) and [(eta5-C5H5)2M]2(micro2,eta2,eta2-N2) complexes cannot react with an H2 molecule for M = Ti, while those for M = Zr and Hf can. It was shown that the difference in the B3LYP (hybrid) and PBE (nonhybrid) calculated energy gaps between the lowest closed-shell singlet and triplet states of the present complexes reduces via first- > second- > third-row transition metals; both hybrid and nonhybrid density functionals can be safely used to describe reactivity of the low-lying low-spin and high-spin states of second- and third-row transition metal complexes. PMID- 17341067 TI - Single-crystal nanoribbons, nanotubes, and nanowires from intramolecular charge transfer organic molecules. AB - Single-crystal one-dimensional (1-D) nanostructures of [2-(p-dimethyl aminophenyl)ethenyl]-phenyl-methylene-propanedinitrile (DAPMP) have been prepared by a simple solution process without the assistance of added surfactant, catalyst, or template under ambient condition. The approach exploits the directional supramolecular interaction induced by strong donor-acceptor dipole dipole supramolecular interaction in the growth of 1-D nanostructures. By varying the process temperatures, the DAPMP nanostructures can be controllably prepared as either nanoribbons, nanotubes, or nanowires with high morphological and chemical purities. Significant changes in optical properties were observed for nanostructures of different morphology. PMID- 17341069 TI - Competitive C-H bond activation and beta-hydride elimination at platinum(II). PMID- 17341068 TI - Single-molecule spectroscopic investigation of energy migration processes in cyclic porphyrin arrays. AB - Covalently linked cyclic porphyrin arrays have been synthesized to mimic natural light-harvesting apparatuses and to investigate the highly efficient energy migration processes occurring in these systems for future applications in molecular photonics. To avoid an ensemble-averaged picture, we performed a single molecule spectroscopic study on the energy migration processes of cyclic porphyrin arrays and a linear model compound embedded in a rigid polymer matrix by recording fluorescence intensity trajectories, by performing coincidence measurements, and by doing wide-field defocused imaging. Our study demonstrates efficient energy migration within the cyclic porphyrin arrays at the single molecule level. By comparison with the data of the linear model compound, we could pinpoint the role of the dipole-dipole coupling between diporphyrin subunits and the rigidity of the cyclic structures on the energy transfer processes. PMID- 17341070 TI - Optimizing the photocatalytic properties of hydrothermal TiO2 by the control of phase composition and particle morphology. a systematic approach. AB - The possibility of controlling the photocatalytic activity of TiO2 nanoparticles by tailoring their crystalline structure and morphology is a current topic of great interest. In this study, a broad variety of well-faceted particles with different phase compositions, sizes, and shapes have been obtained from concentrated TiOCl2 solutions by systematically changing temperature, pH, and duration of the hydrothermal treatment. The guide to select the suitable experimental conditions was provided by thermodynamic modeling based on available thermochemical data. By combining the results of TEM, HRTEM, XRD, density, and specific surface area measurements, a complete structural and morphological characterization of the particles was performed. Correlation between the photocatalytic activity in the UV photodegradation of phenol solutions and the particle size was established. Prismatic rutile particles with length/width ratio around 5 and breadth of 60-100 nm showed the highest activity. The surface chemistry of the particles was also investigated. Treatments that decrease the surface acidity, such as washing the powders with ammonia solution and/or calcining at 400 degrees C, have detrimental effect on photocatalytic activity. The overall results suggest correlation between particle morphology and photocatalytic activity and indicate that both electron-hole recombination and adsorption at the surface can be rate-controlling processes. The systematic approach presented in this study demonstrates that a substantial improvement of the photocatalytic activity of TiO2 can be achieved by a careful design of the particle morphology and the control of the surface chemistry. PMID- 17341071 TI - The inconsistency in adsorption properties and powder XRD data of MOF-5 is rationalized by framework interpenetration and the presence of organic and inorganic species in the nanocavities. AB - MOF-5 is the archetype metal-organic framework and has been subjected to numerous studies the past few years. The focal point of this report is the pitfalls related to the MOF-5 phase identification based on powder XRD data. A broad set of conditions and procedures have been reported for MOF-5 synthesis. These variations have led to materials with substantially different adsorption properties (specific surface areas in the range 700 to 3400 m(2)/g). The relatively low weight loss observed for some as synthesized samples upon solvent removal is also indicative of a low pore volume. Regrettably, these materials have all been described as MOF-5 without any further comments. Furthermore, the reported powder XRD patterns hint at structural differences: The variations in surface area are accompanied by peak splitting phenomena and rather pronounced changes in the relative peak intensities in the powder XRD patterns. In this work, we use single-crystal XRD to investigate structural differences between low and high surface area MOF-5. The low surface area MOF-5 sample had two different classes of crystals. For the dominant phase, Zn(OH)2 species partly occupied the cavities. The presence of Zn species makes the hosting cavity and possibly also adjacent cavities inaccessible and thus efficiently reduces the pore volume of the material. Furthermore, the minor phase consisted of doubly interpenetrated MOF-5 networks, which lowers the adsorption capacity. The presence of Zn species and lattice interpenetration changes the symmetry from cubic to trigonal and explains the peak splitting observed in the powder XRD patterns. Pore-filling effects from the Zn species (and partly the solvent molecules) are also responsible for the pronounced variations in powder XRD peak intensities. This latter conclusion is particularly useful for predicting the adsorption properties of a MOF-5-type material from powder XRD. PMID- 17341072 TI - Reversible single crystal to single crystal transformation through Fe-O(H)Me/Fe OH(2) bond formation/bond breaking in a gas-solid reaction at an ambient condition. PMID- 17341073 TI - Stable exo-nido-metallacarboranes (M = Os(IV)) that incorporate meta-carborane based dicarbollide ligands. AB - Reactions of the [K]+ salts of the [nido-7,9-C2B9H12]- anion (2) and its C phenylated derivative [7-Ph-nido-7,9-C2B9H11]- (4) with [OsCl2(PPh3)3] (3) proceed in benzene at ambient temperature with the formation of 16-electron chlorohydrido-Os(IV) exo-nido complexes, [exo-nido-10,11-{(Ph3P)2OsHCl}-10,11-(mu H)2-7-R-7,9-C2B9H8] (5: R = H; 6: R = Ph), along with the small amounts of the charge-compensated nido-carboranes [nido-7,9-C2B9H11PPh3] (7) and [7-Ph-nido-7,9 C2B9H10PPh3] (8) as byproducts. However, when carried out under mild heating in ethanol, the reaction of 2 with 3 selectively afforded a 16-electron dihydrido Os(IV) exo-nido complex [exo-nido-10,11-{(Ph3P)2OsH2}-10,11-(mu-H)2-7,9-C2B9H9] (9). Structures of both complexes 5 and 9 have been confirmed by single-crystal X ray diffraction studies, which revealed that nido-carboranes in these species function as a bidentate dicarbollide ligands [7-R-nido-7,9-C2B9H10]2- linked to the Os(IV) center via two B-H...Os bonds involving adjacent B-H vertices in the upper CBCBB belt of the carborane cage. Thus, compounds 5 and 9 represent the first structurally characterized exo-nido-metallacarboranes based on meta dicarbollide-type ligands. Variable-temperature 1H and 31P{1H} NMR experiments indicate that complex 9 is fluxional in solution and shows an unusual exchange between terminal Os-(H)2 and bridging {B-H}2...Os hydrogen atoms. Upon heating in d8-THF at 65 degrees C, complex 9 converts irreversibly to its closo isomer [2,2 (PPh3)2-2,2-H2-closo-2,1,7-OsC2B9H11] (13), which could thus be obtained as a pure crystalline solid. The structure of 13 has been established on the basis of analytical and multinuclear NMR data and a single-crystal X-ray diffraction study. PMID- 17341074 TI - A theoretical study of cohesion, structural deformation, inclusion, and dynamics in porous hydrogen-bonded molecular networks. AB - Molecules with multiple sites of hydrogen bonding attached to suitable cores tend to crystallize as open networks. The resulting crystals can have the following unusual properties: They can include significant amounts of guest molecules; the guests are typically located in channels and can be exchanged without loss of crystallinity; and the geometry of the networks can change in response to new guests. We have found that DFT calculations can provide accurate simulations of the unusual structure and properties of such materials, represented by crystals of prototypic tetrapyridinone 1. These calculations have yielded three key insights that cannot be obtained directly from experiments. (1) The hypothetical porous network obtained by removing guests from crystals of compound 1 is highly flexible, and its deformations are inherently anisotropic, leading to lengthening or shortening of the channels along the c axis and no significant changes along the a and b axes. (2) Quantitative analysis of the total cohesive energy has revealed that hydrogen bonding within the network makes a dominant contribution, along with interactions of guests with the network. (3) Differences in the overall stability of crystals of compound 1 as the guests are varied do not arise primarily from significant changes in the cohesive energy of the network itself; instead, differences in guest-guest interactions play a key role, resulting from the nature of the guests and constraints imposed by the surrounding network. These insights, together with the results of ab initio molecular dynamics, help explain how hydrogen-bonded networks can be robust yet permit molecular movement that underlies the exchange of guests and adaptive porosity. These insights promise to be of general value to scientists studying ordered molecular materials in which strong directional interactions are prominent. PMID- 17341075 TI - Chiral proton catalysis: enantioselective Bronsted acid catalyzed additions of nitroacetic acid derivatives as glycine equivalents. PMID- 17341077 TI - Field-effect transistors based on a benzothiadiazole-cyclopentadithiophene copolymer. PMID- 17341076 TI - Radical intermediates in monooxygenase reactions of rieske dioxygenases. PMID- 17341078 TI - Geometry of hydrogen bonds formed by lipid bilayer nitroxide probes: a high frequency pulsed ENDOR/EPR study. PMID- 17341079 TI - EPR study of the low-spin [d(3); S =(1)/(2)], Jahn-Teller-active, dinitrogen complex of a molybdenum trisamidoamine. PMID- 17341080 TI - Photoelectron spectroscopic characterization of the niobium-benzene anion produced by reaction of niobium with ethylene. PMID- 17341081 TI - Titanocene-catalyzed regiodivergent epoxide openings. PMID- 17341082 TI - A memory effect controlled by a pulsed voltage in photoinduced conductivity switching in an organic charge-transfer salt. PMID- 17341083 TI - N- versus O-arylation of aminoalcohols: orthogonal selectivity in copper-based catalysts. PMID- 17341084 TI - Reactivity of individual organolithium aggregates: a RINMR study of n butyllithium and 2-methoxy-6-(methoxymethyl)phenyllithium. PMID- 17341085 TI - Reversible water-induced magnetic and structural conversion of a flexible microporous Ni(II)Fe(III) ferromagnet. PMID- 17341086 TI - "Threading-followed-by-swelling": a new protocol for rotaxane synthesis. PMID- 17341087 TI - Generating patterns for sensing using a single receptor scaffold. PMID- 17341088 TI - Selective layer reaction of layer-by-layer assembled layered double-hydroxide nanocrystals. PMID- 17341089 TI - Ni(0)-promoted hydroxycarboxylation of 1,2-dienes by reaction with CO2 and O2. AB - [structure: see text]. A novel method for the preparation of hydroxy carboxylic acid derivatives has been developed by O2-oxidation of pi-allylnickel intermediates generated by Ni(0)-mediated coupling of 1,2-dienes with CO2. PMID- 17341090 TI - Enantioselective organocatalytic oxidation of functionalized sterically hindered disulfides. AB - [structure: see text]. The first study on enantioselective oxidation of functionalized sterically hindered disulfides is reported. This study shows that the Shi organocatalytic system using carbohydrate-derived ketone with oxone is superior to the Ellman-Bolm vanadium catalyst in terms of chemical yield and enantioselectivity. Whereas the latter system afforded mostly racemic thiosulfinates in low to moderate yields, the former one afforded thiosulfinates with up to 96% ee. PMID- 17341091 TI - Direct intermolecular hydroacylation of N,N-dialkylacrylamides with aldehydes catalyzed by a cationic rhodium(I)/dppb complex. AB - [structure: see text]. A cationic rhodium(I)/dppb complex catalyzed direct intermolecular hydroacylation of N,N-dialkylacrylamides with both aliphatic and aromatic aldehydes has been achieved through the stabilization of acylrhodium intermediates by alkene chelation to rhodium. This method represents a versatile new route to gamma-ketoamides in view of the high atom economy and commercial availability of substrates. PMID- 17341092 TI - Nitrogen isotope composition of organically and conventionally grown crops. AB - Authentic samples of commercially produced organic and conventionally grown tomatoes, lettuces, and carrots were collected and analyzed for their delta15N composition in order to assemble datasets to establish if there are any systematic differences in nitrogen isotope composition due to the method of production. The tomato and lettuce datasets suggest that the different types of fertilizer commonly used in organic and conventional systems result in differences in the nitrogen isotope composition of these crops. A mean delta15N value of 8.1 per thousand was found for the organically grown tomatoes compared with a mean value of -0.1 per thousand for those grown conventionally. The organically grown lettuces had a mean value of 7.6 per thousand compared with a mean value of 2.9 per thousand for the conventionally grown lettuces. The mean value for organic carrots was not significantly different from the mean value for those grown conventionally. Overlap between the delta15N values of the organic and conventional datasets (for both tomatoes and lettuces) means that it is necessary to employ a statistical methodology to try and classify a randomly analyzed "off the shelf" sample as organic/conventional, and such an approach is demonstrated. Overall, the study suggests that nitrogen isotope analysis could be used to provide useful "intelligence" to help detect the substitution of certain organic crop types with their conventional counterparts. However, delta15N analysis of a "test sample" will not provide unequivocal evidence as to whether synthetic fertilizers have been used on the crop but could, for example, in a situation when there is suspicion that mislabeling of conventionally grown crops as "organic" is occurring, be used to provide supporting evidence. PMID- 17341093 TI - Kinetics of the inhibition of fusarium serine proteinases by barley (Hordeum vulgare L.) inhibitors. AB - Fungal infections of barley and wheat cause devastating losses of these food crops. The endogenous proteinase inhibitors produced by plant seeds probably defend the plants from pathogens by inhibiting the degradation of their proteins by the pathogen proteases. We have studied the interactions of barley grain inhibitors with the subtilisin-like and trypsinlike proteinases of Fusarium culmorum. The inhibition kinetics of three inhibitor proteins, chymotrypsin/subtilisin inhibitor 2 (CI-2), barley alpha-amylase/subtilisin inhibitor (BASI), and Bowman-Birk trypsin inhibitor (BBBI), have been studied in detail for the first time using fungal enzymes. The kinetic studies were performed at physiological pH values to mimic in vivo conditions. Numerical approaches to kinetic analyses were used to calculate the inhibition constants, because the data analyses were complicated by some inhibitor turnover and the instability of enzymes and substrates. All were slow, tight-binding inhibitors that followed either a two-step mechanism (CI-2 and BASI) or a single-step mechanism (BBBI) under the conditions investigated. The overall Ki values derived were approximately 50 pM, 1 nM, and 0.1 nM for CI-2, BASI, and BBBI, respectively. The main difference between the CI-2 and the BASI inhibitions was accounted for by the stabilities of their final complexes and the rate constants for their second dissociation steps (9 x 10(-6)/s and 3 x 10(-4)/s, respectively). Understanding the inhibition mechanisms will be valuable in designing improved strategies for increasing the resistance of the grains to fungal infections. PMID- 17341094 TI - Nicotinamide 2-fluoroadenine dinucleotide unmasks the NAD+ glycohydrolase activity of Aplysia californica adenosine 5'-diphosphate ribosyl cyclase. AB - ADP-ribosyl cyclases catalyze the transformation of nicotinamide adenine dinucleotide (NAD+) into the calcium-mobilizing nucleotide second messenger cyclic adenosine diphosphoribose (cADP-ribose) by adenine N1-cyclization onto the C-1' ' position of NAD+. The invertebrate Aplysia californica ADP-ribosyl cyclase is unusual among this family of enzymes by acting exclusively as a cyclase, whereas the other members, such as CD38 and CD157, also act as NAD+ glycohydrolases, following a partitioning kinetic mechanism. To explore the intramolecular cyclization reaction, the novel nicotinamide 2-fluoroadenine dinucleotide (2-fluoro-NAD+) was designed as a sterically very close analogue to the natural substrate NAD+, with only an electronic perturbation at the critical N1 position of the adenine base designed to impede the cyclization reaction. 2 Fluoro-NAD+ was synthesized in high yield via Lewis acid catalyzed activation of the phosphoromorpholidate derivative of 2-fluoroadenosine 5'-monophosphate and coupling with nicotinamide 5'-monophosphate. With 2-fluoro-NAD+ as substrate, A. californica ADP-ribosyl cyclase exhibited exclusively a NAD+ glycohydrolase activity, catalyzing its hydrolytic transformation into 2-fluoro-ADP-ribose, albeit at a rate ca. 100-fold slower than for the cyclization of NAD+ and also, in the presence of methanol, into its methanolysis product beta-1' '-O-methyl 2 fluoro-ADP-ribose with a preference for methanolysis over hydrolysis of ca. 100:1. CD38 likely converted 2-fluoro-NAD+ exclusively into the same product. We conclude that A. californica ADP-ribosyl cyclase can indeed be classified as a multifunctional enzyme that also exhibits a classical NAD+ glycohydrolase function. This alternative pathway that remains, however, kinetically cryptic when using NAD+ as substrate can be unmasked with a dinucleotide analogue whose conversion into the cyclic derivative is blocked. 2-Fluoro-NAD+ is therefore a useful molecular tool allowing dissection of the kinetic scheme for this enzyme. PMID- 17341095 TI - Role of secondary structure in protein-phospholipid surface interactions: reconstitution and denaturation of apolipoprotein C-I:DMPC complexes. AB - Binding of protein to a phospholipid surface is commonly mediated by amphipathic alpha-helices. To understand the role of alpha-helical structure in protein-lipid interactions, we used discoidal lipoproteins reconstituted from dimyristoylphosphatidylcholine (DMPC) and human apolipoprotein C-I (apoC-I, 6 kDa) or its mutants containing single Pro substitutions along the sequence and differing in their alpha-helical content in solution (0-48%) and on DMPC (40 75%). Thermal denaturation revealed that lipoprotein stability correlates weakly with the protein helix content: proteins with higher alpha-helical content on DMPC may form more stable complexes. Lipoprotein reconstitution upon cooling from the heat-denatured state and DMPC clearance studies revealed that protein secondary structure in solution and on DMPC correlates strongly with the maximal temperature of lipoprotein reconstitution: more helical proteins can reconstitute lipoproteins at higher temperatures. Interestingly, at Tc = 24 degrees C of the DMPC gel-to-liquid crystal transition, the clearance rate is independent of the protein helical content. Consequently, if the packing defects at the phospholipid surface are readily available (e.g., at the lipid phase boundary), insertion of protein into these defects is independent of the secondary structure in solution. However, if hydrophobic defects are limited, protein binding and insertion are aided by other surface-bound proteins and depend on their helical propensity: the larger the propensity, the faster the binding and the broader its temperature range. This positive cooperativity in binding of alpha-helices to phospholipid surface, which may result from direct and/or lipid-mediated protein-protein interactions, may be important for lipoprotein metabolism and for protein membrane binding. PMID- 17341096 TI - Mechanism of flavin reduction in the class 1A dihydroorotate dehydrogenase from Lactococcus lactis. AB - Dihydroorotate dehydrogenases (DHODs) oxidize dihydroorotate (DHO) to orotate (OA) using the FMN prosthetic group to abstract a hydride equivalent from C6 and a protein residue (cysteine for class 1A DHODs) to deprotonate C5. The fundamental question of whether the scission of the two DHO C-H bonds is concerted or stepwise was addressed for the class 1A enzyme from Lactococcus lactis by determining kinetic isotope effects (KIEs) on flavin reduction in anaerobic stopped-flow experiments. Isotope effects were determined at two pH values. At pH 7.0, KIEs were approximately 2-fold for DHO labeled singly at the 5 position or the 6-position and approximately 4-fold for DHO labeled at both the 5 and 6-positions. At pH 8.5, the KIEs observed for DHO labeled at the 5-position, the 6-position, and the 5- and 6-positions were approximately 2-, approximately 3 , and approximately 6-fold, respectively. These isotope effects are consistent with a concerted oxidation of DHO. The pH dependence of reduction was also determined, and a pKa of 8.3 was found. This pKa can be attributed to the ionization of the active site cysteine which deprotonates C5 of DHO during the reaction. To further investigate the importance of the active site base, two site directed mutants were also studied: Cys130Ala (removal of the active site base) and Cys130Ser (replacement with the active site base used by class 2 DHODs). Both mutant enzymes exhibited binding affinities for DHO similar to that of the wild type enzyme. Reduction of both mutants was extremely slow compared to that of the wild type; the rate of reduction increased with pH, showing no sign of a plateau. Interestingly, double-deuterium isotope effects on the Cys130Ser mutant also showed a concerted mechanism for flavin reduction. PMID- 17341097 TI - Protolytic reactions on reduction of cytochrome c oxidase studied by ATR-FTIR spectroscopy. AB - Reduction of cytochrome c oxidase is coupled to proton uptake, and the reduced minus-oxidized FTIR spectrum should include signatures of protonation of protolytic centers. The major part of the spectrum shows only small differences between acidic and alkaline conditions, which is consistent with the rather weak pH dependence of the proton uptake stoichiometry. Here we aim at revealing redox state-dependent protonatable sites and present a comprehensive investigation over a wide pH range. The reduced-minus-oxidized transition of cytochrome c oxidase from Paracoccus denitrificans was studied by means of Fourier transform infrared spectroscopy in the pH range 5.2-9.5. Effects of pH were analyzed as the difference between reduced-minus-oxidized FTIR spectra at different pH values. Two pH-dependent processes with apparent pKa values of 6.6 and 8.4 and Hill coefficients 0.9 and 0.1, respectively, were found by this methodology. A sharp OH band appears in the IR "water region" on reduction of the enzyme, independent of pH in the range 6.5-9.0, and downshifted by approximately 940 cm-1 on changing the solvent to D2O and by 10 cm-1 on H216O/H218O isotope exchange. This feature of an asymmetric water molecule may belong to water that is produced in the binuclear center upon reduction or to a structured water molecule that loses a hydrogen bond. PMID- 17341099 TI - Voltammetric and surface-enhanced resonance Raman spectroscopic characterization of cytochrome C adsorbed on a 4-mercaptopyridine monolayer on silver electrodes. AB - To combine voltammetric techniques with surface-enhanced resonance Raman scattering (SERRS), cytochrome c (cyt c) was immobilized on a roughened silver electrode chemically modified with a self-assembled monolayer (SAM) of 4 mercaptopyridine (PySH). All measurements were performed on the same electrode in a homemade spectroelectrochemical cell suitable for such applications. Cyt c on a PySH-SAM shows a quasi-reversible, monoelectronic, adsorption-controlled CV response with a formal reduction potential of -0.061 V (vs SCE), which is comparable to the values found for native cyt c adsorbed on different SAMs. SERRS spectra proved that cyt c adsorbed on a PySH monolayer is present in the native conformer (the B1 state). Voltammetric and SERRS experiments at high ionic strength revealed that the interaction between the SAM and the protein is electrostatic in nature. In conclusion, PySH was found to be suitable for adsorption of cyt c at SERRS-active silver surfaces. In comparison with other SAMs, PySH requires less time (10 min vs 12-18 h) to form a long-time durable and reproducible coating on the roughened electrode surface. PMID- 17341098 TI - Interfacial organizations of gel phospholipid and cholesterol in bovine lung surfactant films. AB - Pulmonary surfactants stabilize the lung by way of reducing surface tension at the air-lung interface of the alveolus. 31P NMR, thin-layer chromatography, and electrospray ionization mass spectroscopy of bovine lipid extract surfactant (BLES) confirmed dipalmitoylphosphatidylcholine (DPPC) to be the major phospholipid species, with significant amounts of palmitoyl oleoylphosphatidylcholine, palmitoyl-myristoylphosphatidylcholine, and palmitoyl oleoylphosphatidylglycerol. BLES and DPPC spread at the air-water interface were studied through surface pressure area, fluorescence, and Brewster angle microscopy measurements. Langmuir-Blodgett films of monomolecular films, deposited on mica, were characterized by atomic force microscopy. BLES films displayed shape, size, and vertical height profiles distinct from those of DPPC alone. Calcium ions in the subphase altered BLES film domain structure. The addition of cholesterol (4 mol %) resulted in the destabilization of compressed BLES films at higher surface pressures (>40 mN m-1) and the formation of multilayered structures, apparently consisting of stacked monolayers. The studies suggested potential roles for individual surfactant lipid components in supramolecular arrangements, which could be the contributing factors in pulmonary surfactant to attain low surface tension at the air-water interface. PMID- 17341100 TI - Bioactive surface modification of mica and poly(dimethylsiloxane) with hydrophobins for protein immobilization. AB - Bioactive surfaces with appropriate hydrophilicity for protein immobilization can be achieved by hydrophobin II (HFBI) self-assembly on mica and polydimethylsiloxane (PDMS) surfaces. X-ray photoelectron spectroscopy and water contact angle measurements illustrated that the surface wettability can be changed from superhydrophobic (PDMS) or superhydrophilic (mica) to moderately hydrophilic, which is suitable for protein (chicken IgG) immobilization on both substrate surfaces. The results suggest that HFBI assembly, one kind of hydrophobin from Trichoderma reesei, may be a versatile and convenient method for the immobilization of biomolecules on diverse substrates, which may have potential applications in biosensors, immunoassays, and microfluidic networks. PMID- 17341101 TI - Initial stages of self-organization of silica-alumina gels in zeolite synthesis. AB - We report the effect of aluminum on the formation and structure of silica nanoparticles formed in basic solutions of small organic and inorganic cations using a combination of small-angle X-ray scattering, conductivity, pH, and 27Al NMR spectroscopy methods. At low silica concentrations, our observations agree with previous reports and show the formation of small oligomers ((HO)4 nAl(OSi(OH)3)n)- that can be modeled qualitatively using a simple aqueous speciation model. We also find that aluminum drastically reduces the concentration of silica at which nanoparticles are formed. Using organic cations, the particles are smaller than the ones observed in pure silica systems (1.5 nm vs approximately 3 nm diameter), but in the case of sodium cations, larger particles are detected ( approximately 10 nm in diameter). The data suggests that sodium cations are incorporated within the inorganic silica/alumina core, as opposed to organic cations that appear to be excluded from such clusters. Important insights are gained by making analogies to the behavior of mixed surfactant systems using regular solution theory and noting that the formation of Si-O-Al bonds (as measured by the DeltaGdegrees(rxn) of condensation) is much more favorable than the formation of Si-O-Si bonds. PMID- 17341102 TI - Thioflavin T and birefringence assays to determine the conversion of proteins into fibrils. AB - The conversion of protein monomers into fibrils can be determined using the centrifugal filtration method. The results of this method were used to calibrate steady-shear birefringence and Thioflavin T fluorescence measurements. For both measurements, a linear correlation with the fibril concentration was extracted, resulting in two fast assays to determine the fibril concentration quantitatively. From birefringence measurements and the conversion determined using the centrifugal filtration method, we were able to calculate more precise values for the birefringence per unit length of the fibrils (M) and the flexibility of the fibrils (beta). PMID- 17341103 TI - Whey protein soluble aggregates from heating with NaCl: physicochemical, interfacial, and foaming properties. AB - Whey protein isolate was heat-treated at 85 degrees C for 15 min at pH ranging from 6.0 to 7.0 in the presence of NaCl in order to generate the highest possible amount of soluble aggregates before insolubility occurred. These whey protein soluble aggregates were characterized for composition, hydrodynamic diameter, apparent molecular weight, zeta-potential, surface hydrophobicity index, activated thiol group content, and microstructure. The adsorption kinetics and rheological properties (E', etad) of these soluble aggregates were probed at the air/water interface. In addition, the gas permeability of a single bubble stabilized by the whey protein soluble aggregates was determined. Finally, the foaming and foam-stabilizing properties of these aggregates were measured. The amount of whey protein soluble aggregates after heat treatment was increased from 75% to 95% from pH 6.0 to pH 7.0 by addition of 5 mM to 120 mM NaCl, respectively. These soluble aggregates involved major whey protein fractions and exhibited a maximum of activated thiol group content at pH > 6.6. The hydrodynamic radius and the surface hydrophobicity index of the soluble aggregates increased from pH 6.0 to 7.0, but the molecular weight and zeta potential decreased. This loss of apparent density was clearly confirmed by microscopy as the soluble aggregates shifted from a spherical/compact structure at pH 6.0 to a more fibrillar/elongated structure at pH 7.0. Surface adsorption was faster for soluble aggregates formed at pH 6.8 and 7.0 in the presence of 100 and 120 mM NaCl, respectively. However, interfacial elasticity and viscosity measured at 0.01 Hz were similar from pH 6.0 to 7.0. Single bubble gas permeability significantly decreased for aggregates generated at pH > 6.6. Furthermore, these aggregates exhibited the highest foamability and foam liquid stability. Air bubble size within the foam was the lowest at pH 7.0. The coarsening exponent, alpha, fell within predicted values of 1/3 and 1/2, except for very dry foams where it was 1/5. PMID- 17341104 TI - Structural stability against disintegration by anionic lipids rationalizes the efficiency of cationic liposome/DNA complexes. AB - Reported here is the correlation between the transfection efficiency of cationic liposome/DNA complexes (lipoplexes) and the structural evolution that they undergo when interacting with anionic membrane lipids. Multicomponent lipoplexes, incorporating from three to six lipid species simultaneously, presented a much higher transfection efficiency than binary lipoplexes, which are more commonly used for gene-delivery purposes. The discovery that a high transfection efficiency can be achieved by employing multicomponent complexes at a lower-than ever-before membrane charge density of lipoplexes was of primary significance. Synchrotron small-angle X-ray diffraction (SAXD) experiments showed that anionic liposomes made of dioleoylphosphatidylglycerol (DOPG) disintegrated the lamellar phase of lipoplexes. DNA unbinding was measured by electrophoresis on agarose gels. Most importantly, structural changes induced by anionic lipids strictly depended on the lipid composition of lipoplexes. We found evidence of the existence of three different regimes of stability related to the interaction between complexes and anionic membranes. Both unstable (with low membrane charge density, sigmaM) and highly stable lipoplexes (with high sigmaM) exhibited low transfection efficiency whereas highly efficient multicomponent lipoplexes exhibited an "optimal stability". This intermediate regime reflects a compromise between two opposing constraints: protection of DNA in the cytosol and endosomal escape. Here we advance the concept that structural stability, upon interaction with cellular anionic lipids, is a key factor governing the transfection efficiency of lipoplexes. Possible molecular mechanisms underlying experimental observations are also discussed. PMID- 17341105 TI - Unique molecular orientation in a smectic liquid crystalline polymer film attained by surface-initiated graft polymerization. AB - Liquid crystalline (LC) polymer brushes containing a mesogenic azobenzene (Az) moiety are synthesized on a quartz or silicon substrate by surface-initiated atom transfer radical polymerization. The molecular orientation of the Az units and the LC properties in the grafted chains are evaluated by UV-vis spectroscopy, polarized optical microscopy, and grazing incidence X-ray diffraction measurements. The Az side chains of the grafted chains exhibited a smectic LC phase in which the smectic layers are oriented perpendicular to the substrate with a parallel orientation of the mesogens. In contrast, a spincast film of the identical LC polymer without grafting to the surface shows layer structures parallel to the substrate. A drastic effect of tethering one end to the substrate on the LC orientation is demonstrated. PMID- 17341106 TI - Convenient synthesis of maleimido-derivatized lanthanide(III) chelates and their use in mercapto group conjugation. AB - Simple synthesis of luminescent europium(III) and terbium(III) chelates tethered to a maleimido function (7, 8) is described. The method is based on the following: (i) synthesis of protected ligands tethered to a maleimido function and their purification on silica gel; (ii) deprotection by acidolysis; (iii) conversion of the deprotected ligands to the corresponding lanthanide(III) chelates by passing them through a column of strong cation exchange resin loaded with the appropriate lanthanide(III) ions. According to this procedure, large quantities of mercapto-selective biomolecule-labeling reactants of high purity can be prepared. PMID- 17341107 TI - Synthesis and biological evaluation of N-substituted quinolinimides, as potential ligands for in vivo imaging studies of delta-opioid receptors. AB - We report here the syntheses of N-substituted quinolinimide derivatives displaying sufficient affinity and high selectivity for delta-opioid receptors. Among 9-subsituted derivatives, one showed much higher selectivity for the delta receptor in binding assays than the delta antagonist methylnaltrindole (6: Ki = 42 nM; micro/delta and kappa/delta > 238 on rat brain membranes) and antagonist properties. This compound was labeled with carbon-11 (t1/2 = 20.4 min) as a potential radioligand for the noninvasive assessment of delta opioid receptors in vivo with positron emission tomography (PET). A high yielding radiosynthesis of [11C]-6, based on the [11C]methyl introduction on the pyridine moiety by a Stille reaction, was described (radiochemical yield = 60 +/- 10%, specific activities = 0.8 to 1.5 Ci/micromol). The in vivo pharmacological profile in rats indicated that the radiotracer crossed the blood-brain barrier but was not stable and underwent rapid degradation in both plasma and brain. No specific binding was consequently revealed. PMID- 17341108 TI - Evaluation of a (99m)Tc-labeled cyclic RGD tetramer for noninvasive imaging integrin alpha(v)beta3-positive breast cancer. AB - Integrin alphavbeta3 plays a critical role in tumor angiogenesis and metastasis. Radiolabeled RGD peptides that are integrin alphavbeta3-specific are very useful for noninvasive imaging of integrin expression in rapidly growing and metastatic tumors. In this study, we determined the binding affinity of E{E[c(RGDfK)]2}2 (tetramer) and its 6-hydrazinonicotinamide conjugate (HYNIC-tetramer) against the binding of 125I-echistatin to the integrin alphavbeta3-positive MDA-MB-435 breast cancer cells. The athymic nude mice bearing MDA-MB-435 xenografts were used to evaluate the potential of ternary ligand complex [99mTc(HYNIC tetramer)(tricine)(TPPTS)] (TPPTS = trisodium triphenylphosphine-3,3',3' ' trisulfonate) as a new radiotracer for imaging breast cancer integrin alphavbeta3 expression by single photon emission computed tomography (SPECT). It was found that the binding affinity of tetramer (IC50 = 51 +/- 11 nM) was slightly higher than that of its dimeric analogue (IC50 = 78 +/- 27 nM) and is comparable to that of the HYNIC-tetramer conjugate (IC50 = 55 +/- 11 nM) within the experimental error. Biodistribution data showed that [99mTc(HYNIC-tetramer)(tricine)(TPPTS)] had a rapid blood clearance (4.61 +/- 0.81 %ID/g at 5 min postinjection (p.i.) and 0.56 +/- 0.12 %ID/g at 120 min p.i.) and was excreted mainly via the renal route. [99mTc(HYNIC-tetramer)(tricine)(TPPTS)] had high tumor uptake with a long tumor retention (5.60 +/- 0.87 %ID/g and 7.30 +/- 1.32 %ID/g at 5 and 120 min p.i., respectively). The integrin alphavbeta3-specificity was demonstrated by co injection of excess E[c(RGDfK)]2, which resulted in a significant reduction in tumor uptake of the radiotracer. The metabolic stability of [99mTc(HYNIC tetramer)(tricine)(TPPTS)] was determined by analyzing urine and feces samples from the tumor-bearing mice at 120 min p.i. In the urine, about 20% of [99mTc(HYNIC-tetramer)(tricine)(TPPTS)] remained intact while only approximately 15% metabolized species was detected in feces. SPECT images displayed significant radiotracer localization in tumor with good contrast as early as 1 h p.i. The high tumor uptake and fast renal excretion make [99mTc(HYNIC tetramer)(tricine)(TPPTS)] a promising radiotracer for noninvasive imaging of the integrin alphavbeta3-positive tumors by SPECT. PMID- 17341109 TI - Proteomic analysis of salivary acidic proline-rich proteins in human preterm and at-term newborns. AB - A 1 year follow-up investigation of salivary acidic proline-rich proteins (aPRPs) in preterm and at-term newborns using HPLC-ESI-IT-MS showed that (i) this class of proteins is constitutive rather than inducible, as it is still found in the oral cavity of preterm newborns from 180 days of postconception age (PCA); (ii) the expression of PRH-2 locus anticipates that of PRH-1, since Db isoforms are expressed some months after the PRP-1 and PRP-2 isoforms. The evaluation of the relative abundances of the different aPRPs isoforms and derivatives (differently phosphorylated and cleaved) as a function of PCA showed that (iii) the proteolytic enzymes generating truncated isoforms are also constitutive because they are fully active since 180 days of PCA; (iv) the kinase involved in aPRP phosphorylation is not fully mature in preterm newborns, but its activity increases with PCA, synchronizing with that of at-term newborns and reaching the adult levels at about 500-600 days of PCA, in concomitance with the beginning of deciduous dentition. PMID- 17341110 TI - Interaction between inducible nitric oxide synthase and calmodulin in Ca2+-free and -bound forms. AB - We have obtained the first direct electrochemistry of full-length inducible nitric oxide synthase (iNOS) by entrapping the enzyme in polyethylenimine (PEI) film. The interaction between iNOS and calmodulin (CaM) was then studied, which revealed an enhanced electron-transfer reactivity of the enzyme facilitated by CaM. It was also found that interflavin electron transfer of iNOS could be activated by the binding of Ca2+-bound CaM. The formal potentials (E degrees ') of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) were determined to be -470 and -284 mV vs SCE at pH 7, respectively. The effect of Ca2+ on the interaction between iNOS and CaM has been examined as well. CaM bound with adequate Ca2+ was shown to have a better capability to enhance the electron transfer reactions within iNOS. PMID- 17341112 TI - Characterization of arabinoxylan-dehydrogenation polymer (synthetic lignin polymer) nanoparticles. AB - Coniferyl alcohol (G monomer) and a mixture of coniferyl alcohol/sinapyl alcohol (GS monomers, 1/1 ratio) were polymerized to dehydrogenation polymers (DHPs) in presence of two structurally related heteroxylans (HX) differing only in their phenolic substitution patterns. One (HX-40) was enriched in ferulate (FA) while the other (HX-90) was almost devoid of FA. The morphology of the resulting nanoparticles was studied by transmission electron microscopy whereas formation of particles was followed by size exclusion chromatography with online multiangle laser light scattering. HX-40-DHP-G- and HX-40-DHP-GS-derived particles display complex morphological patterns whereas HX-90-DHP-G and HX-90-DHP-GS present rather spherical shapes. The determination of particle sizes and molar masses showed that HX-90 samples formed denser particles than HX-40 ones. These differences are discussed in relation to the ferulate substitution level. PMID- 17341113 TI - Effect of aging and ice structuring proteins on the morphology of frozen hydrated gluten networks. AB - The present investigation constitutes an attempt to rationalize the effect of aging and ice structuring proteins (ISPs) on the network morphology of frozen hydrated gluten. In doing so, it employs differential scanning calorimetry, time domain NMR, dynamic oscillation on shear, creep testing, and electron microscopy. Experimentation and first principles modeling allows identification and description of the processes of ice formation and recrystallization in molecular terms. It is demonstrated that in the absence of a readily discernible glass transition temperature in gluten-ice composites, the approach of considering the melting point and aging at constant or fluctuating temperature conditions in the vicinity of this point can provide a valid index of functional quality. A theoretical framework supporting the concept of capillary confined frozen water in the gluten matrix was advanced, and it was found that ISPs were effective in controlling recrystallization both within these confines and within ice in the bulk. PMID- 17341114 TI - Furanocembranoids from the stem bark of Croton oblongifolius. AB - Four novel furanocembranoids (1-4) were isolated from the stem bark of Croton oblongifolius. Their structures were elucidated on the basis of spectroscopic analysis, mainly NMR and MS. Compounds 1, 3, and 4 exhibited good cytotoxicity against several human tumor cell lines. PMID- 17341115 TI - Di(alkoxy)- and di(alkylthio)-substituted perylene-3,4;9,10-tetracarboxy diimides with tunable electrochemical and photophysical properties. AB - Nucleophilic substitution of N,N'-dicyclohexyl-1,7-dibromoperylene-3,4:9,10 tetracarboxydiimide (PTCDI) with an excess of corresponding alkanol in the presence of sodium hydride or anhydrous potassium carbonate at 85-100 degrees C provided both di(alkoxy)- and mono(alkoxy)-substituted PTCDI compounds, namely, N,N'-dicyclohexyl-1,7-di(alkoxy)perylene-3,4:9,10-tetracarboxydiimide (3) and N,N'-dicyclohexyl-1-bromo-7-alkoxyperylene-3,4:9,10-tetracarboxydiimide (2). Starting from mono(alkoxy)-substituted PTCDI, nucleophilic substitution with thiol, thiophenol, or alkylamine led to the formation of unsymmetrical 1,7 di(substituted) PTCDI compounds (7-10). For the purpose of comparative studies, symmetrical di(substituted) N,N'-dicyclohexyl-1,7-di(alkylthio)perylene-3,4:9,10 tetracarboxydiimide (4), N,N'-dicyclohexyl-1,7-di(thiophenyl)perylene-3,4:9,10 tetracarboxydiimide (5), and N,N'-dicyclohexyl-1,7-di(alkylamine)perylene 3,4:9,10-tetracarboxydiimide (6) have also been prepared by a similar nucleophilic substitution. These newly prepared PTCDI compounds have been characterized by a wide range of spectroscopic methods in addition to elemental analysis. Electronic absorption and fluorescence studies revealed that the absorption and emission bands as well as the fluorescence quantum yield can be tuned continuously over a large range by incorporating substituents with different electron-donating abilities. PMID- 17341116 TI - Unexpected steric effects of "remote" alkyl groups on the rate of conjugate additions to alkyl alpha,beta-ethylenic sulfones, sulfoxides, and esters. AB - Examination of conjugated ethylenic sulfones, sulfoxides, and esters in Michael type addition reactions reveals, for the first time, that the size of the heteroatom-attached alkyl group affects the rate of conjugate addition. Molecular modeling strongly suggests that what are generally considered to be "remote" alkyl groups in -CbetaH=CalphaHS(O)n-alkyl systems and -CH2CbetaH=CalphaHCOO alkyl systems are actually not remote from the beta-carbon atom of the Michael accepting unit. Molecular modeling clearly shows that the alkyl groups in these Michael acceptors shield the beta-carbons in the following order: Eti-Pr>t-Bu. PMID- 17341117 TI - Efficient rate enhancement due to intramolecular general base (IGB) assistance in the hydrolysis of N-(o-hydroxyphenyl)phthalimide. AB - The rates of the hydrolyses of N-(o-hydroxyphenyl)phthalimide (1) and N-(o methoxyphenyl)phthalimide (2), studied at different pH, show that the hydrolysis of 1 involves intramolecular general base (IGB) assistance where the o-O- group of ionized 1 acts as IGB and H2O as the reactant. The rate enhancement due to the IGB-assisted reaction of H2O with ionized 1 is>8x10(4)-fold. Pseudo-first-order rate constant for the reaction of water with 2 is approximately 2x10(3)-fold smaller than the first-order rate constant (0.10 s-1) for pH-independent hydrolysis of 1 within the pH range of 9.60-10.10. Second-order rate constants (kOH) for hydroxide ion-assisted hydrolysis of ionized 1 and 2 are 3.0 and 29.1 M 1 s-1, respectively. The solvent deuterium kinetic isotope effect (dKIE) on the rate of alkaline hydrolysis of 1 and 2 reveals that the respective values of kOH/kOD are 0.84 and 0.78, where kOD represents the second-order rate constant for DO--assisted cleavage of these imides (1 and 2). The value of kwH2O/kdD2O is 2.04, with kwH2O and kdD2O representing pseudo-first-order rate constants for the reactions of ionized 1 with H2O and D2O, respectively. PMID- 17341118 TI - Conformational consequences of the dynamic processes in the stereolabile atropisomers of acyl-substituted m-terphenyl derivatives. AB - By means of low-temperature NMR spectroscopy, conformers (stereolabile atropisomers) due to the restricted rotation about the Ar-Ar and Ar-C(O)R bonds were detected in a number of acylphenyl derivatives, substituted in positions 2 and 6 by the 3-isopropylphenyl moiety (compounds 1-3, R=H, Me, and t-Bu, respectively). The conformational assignment was accomplished on the basis of the symmetry of the low-temperature 13C NMR spectra with the added support of ab initio calculations. The interconversion barriers were also determined by complete line shape simulation of the NMR spectra, and the experimental values were satisfactorily reproduced by ab initio calculations. In the case of the asymmetric derivative 4, two enantiomers, generated by the restricted t-BuC(O)-Ar rotation, were found sufficiently stable to allow their separation by means of the enantioselective HPLC technique at ambient temperature and to obtain the corresponding CD spectra. PMID- 17341119 TI - Conventional strain energy in dimethyl-substituted cyclobutane and the gem dimethyl effect. AB - The gem-dimethyl effect is the acceleration of cyclization by substituents in the chain and is often used in organic synthesis as a ring-closing effect. Calculations on cyclobutane, methylcyclobutane, and 1,1-dimethylcyclobutane are performed. 1,1-Dimethylcyclobutane is a four-membered carbon ring with gem dimethyl substituents. Optimum equilibrium geometries, harmonic vibrational frequencies, and corresponding electronic energies are computed for all pertinent molecular systems using SCF theory, density functional theory (DFT), and second order perturbation theory (MP2) with two triple-zeta quality basis sets, 6 311G(d,p) and 6-311G+(2df,2pd). Additional single-point calculations are performed using the optimized MP2/6-311G+(2df,2pd) geometries and coupled-cluster theory including single and double excitations and noniterative, linear triple excitations (CCSD(T)). Calculations indicate that 1,1-dimethylcyclobutane is more than 8 kcal mol-1 less strained than cyclobutane, that is, there is at least some thermodynamic component to the gem-dimethyl effect. PMID- 17341120 TI - BF2 complexes of beta-tetraethyl-substituted dipyrrolyldiketones as anion receptors: potential building subunits for oligomeric systems. AB - Synthesis and anion binding properties of BF2 complexes of beta-tetraethyl substituted dipyrrolyldiketones, with and without electron-withdrawing ethoxycarbonyl moieties at pyrrole alpha-positions, are reported. The substituents at pyrrole rings of these acyclic anion receptors are found to play a key role to control not only the polarization of binding sites (NH and CH) but also the relative stabilities of the preorganized conformations and the degrees of sterical repulsion, both of which notably affect the affinities for anions. PMID- 17341121 TI - 5-aroyl-3,4-dihydropyrimidin-2-one library generation via automated sequential and parallel microwave-assisted synthesis techniques. AB - An efficient two-step synthetic pathway toward the preparation of diversely substituted 5-aroyl-3,4-dihydropyrimidin-2-ones is realized. The protocol involves an initial trimethylsilyl chloride-mediated Biginelli multicomponent reaction involving S-ethyl acetothioacetate, aromatic aldehydes, and ureas as building blocks to generate a set of 3,4-dihydropyrimidine-5-carboxylic acid thiol esters. These thiol esters serve as starting materials for a subsequent Pd catalyzed Cu-mediated Liebeskind-Srogl cross-coupling reaction with boronic acids to provide the desired 5-aroyl-3,4-dihydropyrimidin-2-one derivatives. Both steps were performed using microwave heating in sealed vessels, either in an automated sequential or parallel format using dedicated microwave reactor instrumentation. A diverse library of 30 5-aroyl-3,4-dihydropyrimidin-2-ones was prepared with commercially available aldehyde, urea, and boronic acid building blocks as starting materials. PMID- 17341122 TI - Uniaxial alignment of liquid-crystalline conjugated polymers by nanoconfinement. AB - We demonstrate the uniaxial alignment of a liquid-crystalline conjugated polymer, poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8BT) by means of nanoconfinement during nanoimprinting. The orientation of the conjugated backbones was parallel to the nanolines imprinted into the polymer film. Polarized UV-vis absorption and photoluminescence spectra were measured to quantify the degree of alignment, showing that the polarization ratio and uniaxial molecular order parameter were as high as 66 and 0.97, respectively. The aligned F8BT film was used as the active layer in a PLED, which resulted in polarized electroluminescence with a polarization ratio of 11. Ambipolar PFET in a top-gate configuration with aligned F8BT as the active semiconducting layer showed mobility enhancement when the chains were aligned parallel to the transport direction. Mobility anisotropies for hole and electron transport were 10-15 and 5-7, respectively, for current flow parallel and perpendicular to the alignment direction. PMID- 17341123 TI - Synergetic effects of nanoporous support and urea on enzyme activity. AB - We report synergetic effects of functionalized mesoporous silica (FMS) and urea to promote favorable protein conformational changes. The specific activity of glucose isomerase (GI) entrapped in FMS in the presence of urea was approximately double that of GI in solution in the absence of urea. Rather than losing all activity in a denaturing solution of 8.0 M urea, the specific activity of GI entrapped in FMS remained higher than the highest specific activity of GI free in solution. PMID- 17341124 TI - Reply to comment on "Direct and real-time visualization of the disassembly of a single RecA-DNA-ATPgammaS complex using AFM imaging in fluid". PMID- 17341126 TI - Bone quality: an empty term. PMID- 17341127 TI - A 52-year-old female with a hoarse voice and tingling in the hand. PMID- 17341128 TI - Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. AB - BACKGROUND: Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. METHODS AND FINDINGS: The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y), overweight (body mass index, 27.8 +/- 0.7 kg/m(2)) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR + 12.5% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05). In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005) and 21% +/- 4% in the CREX group (p < 0.004), with no change in the control group (2% +/- 2%). However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid) cycle (citrate synthase), beta-oxidation (beta hydroxyacyl-CoA dehydrogenase), and electron transport chain (cytochrome C oxidase II) was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003) and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011), but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling) induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR. CONCLUSIONS: The observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults. PMID- 17341129 TI - Selection in reported epidemiological risks: an empirical assessment. AB - BACKGROUND: Epidemiological studies may be subject to selective reporting, but empirical evidence thereof is limited. We empirically evaluated the extent of selection of significant results and large effect sizes in a large sample of recent articles. METHODS AND FINDINGS: We evaluated 389 articles of epidemiological studies that reported, in their respective abstracts, at least one relative risk for a continuous risk factor in contrasts based on median, tertile, quartile, or quintile categorizations. We examined the proportion and correlates of reporting statistically significant and nonsignificant results in the abstract and whether the magnitude of the relative risks presented (coined to be consistently > or =1.00) differs depending on the type of contrast used for the risk factor. In 342 articles (87.9%), > or =1 statistically significant relative risk was reported in the abstract, while only 169 articles (43.4%) reported > or =1 statistically nonsignificant relative risk in the abstract. Reporting of statistically significant results was more common with structured abstracts, and was less common in US-based studies and in cancer outcomes. Among 50 randomly selected articles in which the full text was examined, a median of nine (interquartile range 5-16) statistically significant and six (interquartile range 3-16) statistically nonsignificant relative risks were presented (p = 0.25). Paradoxically, the smallest presented relative risks were based on the contrasts of extreme quintiles; on average, the relative risk magnitude was 1.41 , 1.42-, and 1.36-fold larger in contrasts of extreme quartiles, extreme tertiles, and above-versus-below median values, respectively (p < 0.001). CONCLUSIONS: Published epidemiological investigations almost universally highlight significant associations between risk factors and outcomes. For continuous risk factors, investigators selectively present contrasts between more extreme groups, when relative risks are inherently lower. PMID- 17341130 TI - A burst-based "Hebbian" learning rule at retinogeniculate synapses links retinal waves to activity-dependent refinement. AB - Patterned spontaneous activity in the developing retina is necessary to drive synaptic refinement in the lateral geniculate nucleus (LGN). Using perforated patch recordings from neurons in LGN slices during the period of eye segregation, we examine how such burst-based activity can instruct this refinement. Retinogeniculate synapses have a novel learning rule that depends on the latencies between pre- and postsynaptic bursts on the order of one second: coincident bursts produce long-lasting synaptic enhancement, whereas non overlapping bursts produce mild synaptic weakening. It is consistent with "Hebbian" development thought to exist at this synapse, and we demonstrate computationally that such a rule can robustly use retinal waves to drive eye segregation and retinotopic refinement. Thus, by measuring plasticity induced by natural activity patterns, synaptic learning rules can be linked directly to their larger role in instructing the patterning of neural connectivity. PMID- 17341131 TI - The gene vitellogenin has multiple coordinating effects on social organization. AB - Temporal division of labor and foraging specialization are key characteristics of honeybee social organization. Worker honeybees (Apis mellifera) initiate foraging for food around their third week of life and often specialize in collecting pollen or nectar before they die. Variation in these fundamental social traits correlates with variation in worker reproductive physiology. However, the genetic and hormonal mechanisms that mediate the control of social organization are not understood and remain a central question in social insect biology. Here we demonstrate that a yolk precursor gene, vitellogenin, affects a complex suite of social traits. Vitellogenin is a major reproductive protein in insects in general and a proposed endocrine factor in honeybees. We show by use of RNA interference (RNAi) that vitellogenin gene activity paces onset of foraging behavior, primes bees for specialized foraging tasks, and influences worker longevity. These findings support the view that the worker specializations that characterize hymenopteran sociality evolved through co-option of reproductive regulatory pathways. Further, they demonstrate for the first time how coordinated control of multiple social life-history traits can originate via the pleiotropic effects of a single gene that affects multiple physiological processes. PMID- 17341132 TI - Retinal ganglion cells can rapidly change polarity from Off to On. AB - Retinal ganglion cells are commonly classified as On-center or Off-center depending on whether they are excited predominantly by brightening or dimming within the receptive field. Here we report that many ganglion cells in the salamander retina can switch from one response type to the other, depending on stimulus events far from the receptive field. Specifically, a shift of the peripheral image--as produced by a rapid eye movement--causes a brief transition in visual sensitivity from Off-type to On-type for approximately 100 ms. We show that these ganglion cells receive inputs from both On and Off bipolar cells, and the Off inputs are normally dominant. The peripheral shift strongly modulates the strength of these two inputs in opposite directions, facilitating the On pathway and suppressing the Off pathway. Furthermore, we identify certain wide-field amacrine cells that contribute to this modulation. Depolarizing such an amacrine cell affects nearby ganglion cells in the same way as the peripheral image shift, facilitating the On inputs and suppressing the Off inputs. This study illustrates how inhibitory interneurons can rapidly gate the flow of information within a circuit, dramatically altering the behavior of the principal neurons in the course of a computation. PMID- 17341133 TI - Arkadia enhances Nodal/TGF-beta signaling by coupling phospho-Smad2/3 activity and turnover. AB - Regulation of transforming growth factor-beta (TGF-beta) signaling is critical in vertebrate development, as several members of the TGF-beta family have been shown to act as morphogens, controlling a variety of cell fate decisions depending on concentration. Little is known about the role of intracellular regulation of the TGF-beta pathway in development. E3 ubiquitin ligases target specific protein substrates for proteasome-mediated degradation, and several are implicated in signaling. We have shown that Arkadia, a nuclear RING-domain E3 ubiquitin ligase, is essential for a subset of Nodal functions in the embryo, but the molecular mechanism of its action in embryonic cells had not been addressed. Here, we find that Arkadia facilitates Nodal signaling broadly in the embryo, and that it is indispensable for cell fates that depend on maximum signaling. Loss of Arkadia in embryonic cells causes nuclear accumulation of phospho-Smad2/3 (P-Smad2/3), the effectors of Nodal signaling; however, these must be repressed or hypoactive as the expression of their direct target genes is reduced or lost. Molecular and functional analysis shows that Arkadia interacts with and ubiquitinates P-Smad2/3 causing their degradation, and that this is via the same domains required for enhancing their activity. Consistent with this dual function, introduction of Arkadia in homozygous null (-/-) embryonic stem cells activates the accumulated and hypoactive P-Smad2/3 at the expense of their abundance. Arkadia-/- cells, like Smad2-/- cells, cannot form foregut and prechordal plate in chimeras, confirming this functional interaction in vivo. As Arkadia overexpression never represses, and in some cells enhances signaling, the degradation of P-Smad2/3 by Arkadia cannot occur prior to their activation in the nucleus. Therefore, Arkadia provides a mechanism for signaling termination at the end of the cascade by coupling degradation of P-Smad2/3 with the activation of target gene transcription. This mechanism can account for achieving efficient and maximum Nodal signaling during embryogenesis and for rapid resetting of target gene promoters allowing cells to respond to dynamic changes in extracellular signals. PMID- 17341134 TI - Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons. AB - Neurotrophins are key regulators of neuronal survival and differentiation during development. Activation of their cognate receptors, Trk receptors, a family of receptor tyrosine kinases (RTKs), is pivotal for mediating the downstream functions of neurotrophins. Recent studies reveal that cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase, may modulate RTK signaling through phosphorylation of the receptor. Given the abundant expression of both Cdk5 and Trk receptors in the nervous system, and their mutual involvement in the regulation of neuronal architecture and synaptic functions, it is of interest to investigate if Cdk5 may also modulate Trk signaling. In the current study, we report the identification of TrkB as a Cdk5 substrate. Cdk5 phosphorylates TrkB at Ser478 at the intracellular juxtamembrane region of TrkB. Interestingly, attenuation of Cdk5 activity or overexpression of a TrkB mutant lacking the Cdk5 phosphorylation site essentially abolishes brain-derived neurotrophic factor (BDNF)-triggered dendritic growth in primary hippocampal neurons. In addition, we found that Cdk5 is involved in BDNF-induced activation of Rho GTPase Cdc42, which is essential for BDNF-triggered dendritic growth. Our observations therefore reveal an unanticipated role of Cdk5 in TrkB-mediated regulation of dendritic growth through modulation of BDNF-induced Cdc42 activation. PMID- 17341135 TI - Expanding the neuron's calcium signaling repertoire: intracellular calcium release via voltage-induced PLC and IP3R activation. AB - Neuronal calcium acts as a charge carrier during information processing and as a ubiquitous intracellular messenger. Calcium signals are fundamental to numerous aspects of neuronal development and plasticity. Specific and independent regulation of these vital cellular processes is achieved by a rich bouquet of different calcium signaling mechanisms within the neuron, which either can operate independently or may act in concert. This study demonstrates the existence of a novel calcium signaling mechanism by simultaneous patch clamping and calcium imaging from acutely isolated central neurons. These neurons possess a membrane voltage sensor that, independent of calcium influx, causes G-protein activation, which subsequently leads to calcium release from intracellular stores via phospholipase C and inositol 1,4,5-trisphosphate receptor activation. This allows neurons to monitor activity by intracellular calcium release without relying on calcium as the input signal and opens up new insights into intracellular signaling, developmental regulation, and information processing in neuronal compartments lacking calcium channels. PMID- 17341136 TI - The prethalamus is established during gastrulation and influences diencephalic regionalization. AB - The vertebrate neural plate contains distinct domains of gene expression, prefiguring the future brain areas. In this study, we draw an extended expression map of the rostral neural plate that reveals discrete domains inside the presumptive posterior forebrain. We show, by fate mapping, that these well defined cell populations will develop into specific diencephalic regions. To address whether these early subterritories are already committed to restricted identities, we began to analyse the consequences of ablation and transplantation of these specific cell populations. We found that precursors of the prethalamus are already specified and irreplaceable at late gastrula stage, because ablation of these cells results in loss of prethalamic markers. Moreover, when transplanted into the ectopic environment of the presumptive hindbrain, these cells still pursue their prethalamic differentiation program. Finally, transplantation of these precursors, in the rostral-most neural epithelium, induces changes in cell identity in the surrounding host forebrain. This cell-non autonomous property led us to propose that these committed prethalamic precursors may play an instructive role in the regionalization of the developing diencephalon. PMID- 17341137 TI - Systemic bud induction and retinoic acid signaling underlie whole body regeneration in the urochordate Botrylloides leachi. AB - Regeneration in adult chordates is confined to a few model cases and terminates in restoration of restricted tissues and organs. Here, we study the unique phenomenon of whole body regeneration (WBR) in the colonial urochordate Botrylloides leachi in which an entire adult zooid is restored from a miniscule blood vessel fragment. In contrast to all other documented cases, regeneration is induced systemically in blood vessels. Multiple buds appear simultaneously in newly established regeneration niches within vasculature fragments, stemming from composites of pluripotent blood cells and terminating in one functional zooid. We found that retinoic acid (RA) regulates diverse developmental aspects in WBR. The homologue of the RA receptor and a retinaldehyde dehydrogenase-related gene were expressed specifically in blood cells within regeneration niches and throughout bud development. The addition of RA inhibitors as well as RNA interference knockdown experiments resulted in WBR arrest and bud malformations. The administration of all-trans RA to blood vessel fragments resulted in doubly accelerated regeneration and multibud formation, leading to restored colonies with multiple zooids. The Botrylloides system differs from known regeneration model systems by several fundamental criteria, including epimorphosis without the formation of blastema and the induction of a "multifocal regeneration niche" system. This is also to our knowledge the first documented case of WBR from circulating blood cells that restores not only the soma, but also the germ line. This unique Botrylloides WBR process could serve as a new in vivo model system for regeneration, suggesting that RA signaling may have had ancestral roles in body restoration events. PMID- 17341139 TI - Performance-based measures: the early results are in. AB - BACKGROUND: Pay for performance (P4P) initiatives are designed to foster and reward improvement in health care delivery. These programs promote "value-based health care" by rewarding quality care that is characterized by a reduced amount of disproportionate spending. OBJECTIVE: To review the intent and design of P4P initiatives as well as the design and results of P4P programs in current practice. SUMMARY: Three key principles are fundamental to building a value-based health care system: measurement, transparency, and accountability. There are several levers currently driving P4P, each influencing the movement in its own way. Among these are employers, federal agencies such as the Centers for Medicare & Medicaid Services and the Department of Health and Human Services, health plans, providers, accreditors, and Congress. One key player in the P4P movement, the National Committee for Quality Assurance (NCQA), is a private, independent nonprofit health care quality oversight organization that measures and reports on health care quality and unites diverse groups around a common goal: improving health care quality. NCQA, has demonstrated several successful provider-level measurement initiatives connected to P4P programs, notable among them Bridges to Excellence programs in several markets, physician recognition programs, the Integrated Healthcare Association's P4P initiative in California, the National Forum on Performance Benchmarking of Physician Offices and Organizations, and health plan accreditation. CONCLUSIONS: The initial data from developmental P4P programs across the nation have indicated that both financial and nonfinancial incentives motivate significant change in health care delivery, but the return on investment of these initiatives is not yet known. PMID- 17341138 TI - Modification of a hydrophobic layer by a point mutation in syntaxin 1A regulates the rate of synaptic vesicle fusion. AB - Both constitutive secretion and Ca(2+)-regulated exocytosis require the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes. At present, little is known about how the SNARE complexes mediating these two distinct pathways differ in structure. Using the Drosophila neuromuscular synapse as a model, we show that a mutation modifying a hydrophobic layer in syntaxin 1A regulates the rate of vesicle fusion. Syntaxin 1A molecules share a highly conserved threonine in the C-terminal +7 layer near the transmembrane domain. Mutation of this threonine to isoleucine results in a structural change that more closely resembles those found in syntaxins ascribed to the constitutive secretory pathway. Flies carrying the I254 mutant protein have increased levels of SNARE complexes and dramatically enhanced rate of both constitutive and evoked vesicle fusion. In contrast, overexpression of the T254 wild-type protein in neurons reduces vesicle fusion only in the I254 mutant background. These results are consistent with molecular dynamics simulations of the SNARE core complex, suggesting that T254 serves as an internal brake to dampen SNARE zippering and impede vesicle fusion, whereas I254 favors fusion by enhancing intermolecular interaction within the SNARE core complex. PMID- 17341140 TI - Merging P4P and disease management: how do you know which one is working? AB - BACKGROUND: An intervention movement in managed care, disease management (DM), is a system of coordinated health care interventions and communication for populations with conditions in which patient self-care efforts are significant. Another managed care intervention movement, pay for performance (P4P), involves an incentive component in which payment is defined based on meeting specific, previously agreed-upon process or outcomes targets. OBJECTIVE: To explore the various characteristics of DM and P4P interventions, determine how they differ, and explore the differences in results of programs in current practice. SUMMARY: In DM, regular ongoing evaluation of clinical, humanistic, and economic outcomes plays a crucial role in reducing costs and improving quality of care. The goal of improving overall patient health in DM is also accomplished by supporting the physician or practitioner/patient relationship and plan of care. P4P initiatives vary more according to the needs and preferences of local providers and plans than do DM initiatives. While DM programs can be implemented without necessarily changing how providers deliver health care, P4P requires new programs and/or systems within the provider sector to improve patient care quality and/or efficiency. P4P initiatives also typically involve the upside or downside risk by physicians/hospitals. Partners HealthCare, based in Boston, features P4P initiatives for inpatient admissions, diabetes, and radiology that have all been met with success. CONCLUSIONS: Both DM and P4P initiatives have been successful in managed care. However, in terms of determining whether DM or P4P initiatives are more effective in improving the quality and efficiency of health care delivery, it is simply too early to tell at this time. PMID- 17341141 TI - Clinical case study: achieving long-term control of insulin resistance. AB - BACKGROUND: A total of 20.8 million people in the United States have diabetes, including 10.3 million adults over the age of 60 years, and more than 6 million people remain undiagnosed. Although diabetes is widely recognized as a prevalent and serious disease in managed care, current care is suboptimal, with less than 2% of American adults with diabetes receiving optimal quality of care. OBJECTIVE: To review the various treatment interventions available in diabetes care, including the use of pay for performance (P4P) initiatives. SUMMARY: In an effort to improve the current state of diabetes care, the NCQA's Health Plan Employer Data and Information Set (HEDIS) diabetes measure was developed as a means to better promote monitoring of various clinical markers in patients with this disease. This measure has been employed in P4P initiatives across the country by granting incentives to providers who have a prespecified proportion of their patients with diabetes meeting the measure. Likewise, to improve outcomes, many experimental and recently approved treatment options for diabetes target different processes in the course of the disease. CONCLUSIONS: An effective program for the management of a diabetes patient population must be multidisciplinary, coordinating the efforts of many different levels of health care providers. Furthermore, components commonly incorporated in P4P initiatives, such as patient self-management education, provider contact, and the use of the American Diabetes Association standards of care measures for screening and lab levels, are imperative to the success of a diabetes management program. PMID- 17341142 TI - Pharmacy management approach: how do we align all the incentives? AB - BACKGROUND: While health care costs continue to rise and shift toward employers, a parallel improvement in health care quality has not been evident. As a means to repair this apparent disconnect, pay for performance (P4P) initiatives are being implemented across the country. OBJECTIVE: To explore the need for P4P in the current state of health care delivery and review the design, components, and results of P4P programs. SUMMARY: In P4P, clinical evidence is used by managed care organizations (MCOs) to drive financial incentives and align physicians and MCO goals, thereby improving delivery of care. At the center of all P4P programs are specific metrics, employed to measure the quality of care by which incentives are provided. These metrics fall into 4 main categories: clinical, patient satisfaction, efficiency, and technology. After metrics are employed and a provider is determined to be deserving of an incentive according to the P4P program in place, several different options exist and vary by plan in terms of incentive type. Primarily, these types of incentives include bonuses, adjustable fee schedules, and withholds. SelectHealth, a nonprofit health insurance company serving members in Utah and Idaho, implemented a primary care incentive program in 2002 for several different conditions and for pharmacy utilization that has been successful to date. CONCLUSIONS: While P4P programs are becoming increasingly common in managed care, challenges still remain, and data on whether these initiatives improve outcomes and manage costs is still limited. PMID- 17341144 TI - AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist. AB - PURPOSE AND METHODS: The aim of this study was to determine the ocular pharmacological characteristics of AL-34662 (1-((S)-2-aminopropyl)-1H-indazole-6 ol), a new synthetic serotonin-2 (5-HT2) receptor-agonist ocular hypotensive agent. A variety of well-documented in vitro and in vivo procedures were utilized to study the pharmacological attributes of AL-34662. RESULTS: AL-34662 exhibited a high affinity for the rat and human 5-HT2 receptor (IC50=0.8-1.5 nM) and for cloned human 5-HT2A-C receptors (IC50=3-14.5 nM). AL-34662 stimulated phosphoinositide turnover in human ciliary muscle (h-CM; EC50=289+/-80 nM) and in human trabecular meshwork (h-TM; EC50=254+/-50 nM) cells. AL-34662 also mobilized intracellular Ca2+ ([Ca2+]i) in h-CM (EC50=140+/-23 nM) and h-TM (EC50=38+/-8 nM) cells, being a full agonist like 5-HT itself. AL-34662's effects in the h-CM (and h-TM) cells were potently antagonized by 5-HT2A-antagonist M-100907 (IC50=1.8+/ 0.7 nM), but weakly by 5-HT2B-antagonist (RS-127445 IC50>10 microM), 5-HT2B/C- antagonist (SB-242084 IC50=2.08 microM) and 5-HT2C antagonist (RS-102221 IC50>1 microM). AL-34662 caused relatively minimal ocular discomfort and hyperemia in rabbit and guinea pig eyes. It efficaciously lowered intraocular pressure (IOP) in the conscious ocular hypertensive monkey eyes (33% at 300 microg). The (R) enantiomer (AL-34707) and the racemate (AL-34497) were less potent and/or efficacious than AL-34662 in all of these assays. CONCLUSIONS: AL-34662 is a high affinity 5-HT2 receptor agonist that potently mobilizes [Ca2+]i in h-CM and h-TM cells, and which efficaciously lowers IOP in conscious ocular hypertensive cynomolgus monkey eyes through a local effect with minimal side-effects. PMID- 17341145 TI - Effects of topoisomerase II inhibitors on retinal pigment epithelium and experimental proliferative vitreoretinopathy. AB - AIMS: The aim of this study was to compare the effect of several commercially available topoisomerase II inhibitors on the proliferation of retinal pigment epithelium (RPE) cells in vitro and to test the toxicity and efficacy of the inhibitor against experimental proliferative vitreoretinopathy (PVR). METHODS: Three different topoisomerase II inhibitors (etoposide, doxorubicin, and daunorubicin) were tested in vitro. Rabbit RPE cells were cultured with or without the drugs at various concentrations. An MTT assay was used to determine the cell viability at 48 h and 96 h. Etoposide, a drug which showed a broad therapeutic range in vitro, was injected to the rabbit eye for the evaluation of the toxicity in vivo. Therapeutic effects of an intravitreal injection of etoposide were evaluated in an experimental PVR model induced by the intravitreal implantation of RPE cells in rabbits. RESULTS: All tested topoisomerase II inhibitors showed a significant reduction of cell viability in vitro. The slope of the dose-response curve was slowly declined for etoposide, and declined sharply for doxorubicin and daunorubicin. Therefore, etoposide was selected for further toxicity and efficacy studies in vivo. There was no significant change in b-wave amplitudes in the etoposide-injected eyes (0.02 mg, 10 microg/mL) after 2 weeks, but a significant reduction occurred in the etoposide-injected eyes (0.2 mg, 100 microg/mL). In the study of the experimental model of PVR, the rabbit eyes injected with RPE cells and etoposide (0.02 mg, 10 microg/mL) showed a significantly lower grading of PVR than that of the control eyes (injected RPE cells and PBS). CONCLUSIONS: These results indicate that etoposide would be an adjunctive for the prevention of PVR. Further pharmacokinetic study of the intravitreal injection of etoposide is required. PMID- 17341146 TI - Paradoxical effect of phentolamine on aqueous flow in the rabbit. AB - PURPOSE: The aim of this study was to assess the effects of acute systemic, nonselective alpha-adrenergic blockade on aqueous flow. METHODS: This study used pentobarbital-anesthetized rabbits (n=7), in which the following parameters were measured: mean arterial pressure, carotid blood flow, heart rate, intraocular pressure (IOP), orbital venous pressure (OVP), ciliary blood flow, and aqueous flow (AqFlow). Measurements were made before and after an intravenous administration of phentolamine (0.1 mg/kg). RESULTS: Phentolamine caused significant decreases in IOP -23%+/-2%; P<0.01), OVP (-28%+/-12%; P<0.05), and AqFlow (-33%+/-6%; P<0.01). The other parameters were not significantly altered. The rapidity of the OVP and IOP responses were noteworthy, being essentially complete 60 s after the phentolamine injection. CONCLUSIONS: A subpressor dose of phentolamine has complex effects on ocular hydrodynamics. The initial IOP decrease is too fast to be explained by aqueous dynamics or ocular rigidity, and so is most likely a result of the disgorgement of choroidal blood volume caused by decreased venous pressure outside the eye. The more prolonged ocular hypotensive effect is explained by the decrease in AqFlow, and perhaps a decrease in episcleral venous pressure or increase in uveoscleral outflow. However, the inhibition of aqueous production is odd, as lost prejunctional inhibition of norepinephrine release and unopposed beta-receptor activation should have increased aqueous production. PMID- 17341147 TI - Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca. AB - PURPOSE: The aim of this study was to compare the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, doxycycline, and artificial tears for the treatment of ocular surface damage in the Botulinum toxin B (BTX-B) induced mouse model of dry eye. METHODS: CBA/J mice were randomized into 2 experimental groups of 35 animals each. The control group received a transconjunctival injection of 0.05 mL of saline into the left lacrimal gland, and another group was injected with 0.05 mL of 20 milliunits BTX-B solution (SPSS, Inc., Chicago, IL). Three (3) days after intralacrimal gland injections, each group was equally randomized into 7 subgroups (n=5 each) to receive treatment unilaterally into their left eyes with topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, 0.4% ketorolac, 0.09% bromfenac, 0.1% diclofenac, or 0.025% doxycycline. Tear volume, ocular surface changes, and spontaneous blink rate were evaluated in each of the 14 experimental subgroups. RESULTS: Topical fluorometholone, nepafenac, and doxycycline significantly improved corneal surface staining in the BTX-B-injected mice within 2 weeks of treatment. Topical ketorolac, diclofenac, and bromfenac, applied twice-daily, partially reduce corneal staining, and did so more slowly by the 4-week time point. In comparison, topical artificial tear-treated mice did not demonstrate significant improvement of the corneal surface at any time point. Aqueous tear production in the BTX-B-injected fluorometholone-treated group started to return to baseline level within 2 weeks, although not significantly. Meanwhile, BTX-B-injected mice treated with artificial tears, topical NSAIDs, and doxycycline still exhibited a reduction in tear production up to 4 weeks. No significant differences in blink rate between the control and study groups undergoing the various treatments were noted at all time points. CONCLUSIONS: This study suggests the potential usefulness of topical NSAIDs, corticosteroid, and doxycycline for the clinical treatment of ocular surface epithelial disorders associated with dry eye. PMID- 17341148 TI - Hypothermia protects cultured human retinal pigment epithelial cells against indocyanine green toxicity. AB - PURPOSE: The aim of this study was to determine whether indocyanine green (ICG) is toxic to cultured human retinal pigment epithelial (ARPE-19) cells, and whether hypothermia can protect the ARPE-19 cells against the ICG toxicity. METHODS: Cultured ARPE-19 cells were exposed to 0.25, 0.5, 1, 2.5, and 5 mg/mL of ICG dye at 37 and 4 degrees C for 30 min. The percentage of ARPE-19 cells that survived was determined by resazurin 1 day after the exposure. RESULTS: Exposure of the RPE cells to a hypotonic saline solution with an osmolarity equal to 5 mg/mL of ICG did not induce a statistically significant decrease in the percentage of RPE cells that survived. Exposure of the ARPE-19 cells to ICG induced a significant decrease in the percentage of cell survival at all concentrations of ICG (P<0.05), except in 0.25 mg/mL at 37 degrees C. At 4 degrees C, on the other hand, ICG induced a statistically significant decrease in the percentage of RPE cell survival only at 5 mg/mL of ICG (P<0.05). CONCLUSIONS: These results indicate that ICG is toxic to human RPE cells in culture, and that cell death cannot be attributed to the low osmolarity. Hypothermia of 4 degrees C has a protective effect against ICG toxicity. PMID- 17341149 TI - In vitro amoebicidal activity of propolis on Acanthamoeba castellanii. AB - PURPOSE: The aim of this study was to investigate the in vitro effects of an ethanolic extract of propolis on the growth and adherence of Acanthamoeba castellanii trophozoites and cysts. METHODS: The effect of propolis with concentrations of 8.0, 6.0, 5.0, 4.0, 3.0, and 2.0 mg/mL on the proliferation of A. castellanii trophozoites, and with a concentration of 62.25, 31.25, 15.62, 7.81, 3.90, 1.95, and 0.97 mg/mL on the proliferation of A. castellanii cysts, at 1, 3, 6, 12, 24, 48, and 72 h were examined in vitro. RESULTS: After 1-72 h, incubation in concentrations between 2.0 and 6.0 mg/mL, its effect was amoebistatic; at concentrations of 8.0 mg/mL and higher, its effect was amoebicidal. After 48 h or longer incubation times at 15.62 mg/mL and at higher concentrations, the propolis extract was cysticidal. At concentrations of 1.97 mg/mL or lower, there was no observable effect at any time point. CONCLUSIONS: These findings indicate that ethanolic extract of propolis has amoebicidal, as well as cysticidal, properties for Acanthamoeba trophozoites and cysts. Propolis alone, or in combination with other amoebicidal agents, may be used in clinical practice after further investigations. PMID- 17341150 TI - Evaluation of subretinal triamcinolone acetonide in patients with exudative age related macular degeneration. AB - PURPOSE: The aim of this paper was to present the results of subretinal delivery of triamcinolone acetonide (TCA) in humans with choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). METHODS: Twenty two (22) eyes of 22 patients underwent pars plana vitrectomy with subretinal TCA administration. Two milligrams (2 mg) of preservative-free TCA were delivered through a 32-gauge automatic subretinal injector in 20 microL of volume. Visual acuity, fluorescein angiography (FA), and intraocular pressure (IOP) were recorded and compared pre- and postoperatively. RESULTS: Preoperative average+/ standard deviation visual acuity in the treated eye was 1.408+/-0.129 (logMAR; median 20/400) and 1.403+/-0.114 (logMAR; median 20/300) postoperatively (P=0.51). The mean area of pre- and postoperative FA leakage in the operated eyes was 21.31+/-1.125 and 19.29+/-1.108 mm2, respectively (P=0.04). The average IOP value before treatment was 15.3+/-0.78 mmHg. Three (3) months after surgery, it was 20.5+/-2.04 mmHg (P=0.02). Six (6) months and 1 year after surgery, the average IOP was 17.0+/-0.66 mmHg (P=0.9) and 15.6+/-1.02 mmHg (P=0.6), respectively. CONCLUSIONS: Subretinal TCA stabilizes visual acuity, decreases FA leakage in eyes with CNV owing to AMD, and does not increase IOP, as seen with intravitreous injections. PMID- 17341151 TI - Infrared spectroscopic examination of aqueous humor. AB - OBJECTIVE: The aim of this study was to report on a new technique for examining aqueous humor. PARTICIPANTS: Aqueous humor samples obtained from 198 patients (cataract: n=66 eyes; age-related macular degeneration [AMD]: n=66; diabetic macular edema: n=66) were in vitro examined by mid infrared spectroscopy. After training and validating the technique, 66 samples were taken for the final independent prediction. RESULTS: In computerized analysis of the spectrometric data, 22 (100%) cataract eyes were diagnosed as the cataract group, 17 (77%) diabetic macular edema eyes were diagnosed as the diabetic macular edema group, and 14 (64%) eyes with AMD were diagnosed as the AMD group. Mid infrared spectrometry could statistically significantly (P=0.004) differentiate between the 3 study groups. CONCLUSIONS: Mid infrared spectroscopic examination of aqueous humor may be able to differentiate eyes with cataract, AMD, or diabetic macular edema. PMID- 17341152 TI - Intravitreal toxicity of high-dose etanercept. AB - PURPOSE: The aim of this study was to evaluate the retinal toxicity of high-dose intravitreal etanercept, a U.S. Food and Drug Administration-approved anti inflammatory drug, in the rabbit model. METHODS: Twenty (20) New Zealand albino rabbits were divided into 5 groups (n=4); eyes in each group were intravitreally injected with one of the following doses of etanercept: 125 microg, 250 microg, 500 microg, 1 mg, or 2.5 mg. One (1) eye in each animal was used for the study dose; the fellow eye was injected with buffered sterile saline as a control. All animals were examined using indirect ophthalmoscopy and slit-lamp biomicroscopy before and after intravitreal injection and at days 1, 7, and 14. Electroretinography (ERG) was performed on all animals before intravitreal injection and 14 days after injection. The animals were euthanized on day 14. Histological preparations of the enucleated eyes were examined with light microscopy for retinal toxicity. RESULTS: Clinical examination, histological evaluation, and ERG results of all 5 groups demonstrated no signs of retinal toxicity. CONCLUSIONS: Intravitreal doses as high as 2.5 mg of etanercept did not cause retinal toxicity. Intravitreal doses of up to 2.5 mg of etanercept may provide a more potent, prolonged effect than the lower doses previously recommended. PMID- 17341153 TI - Age-dependent retinal capillary pericyte degeneration in galactose-fed dogs. AB - The galactose-fed beagle develops diabetes-like microvascular changes that are histologically and clinically similar in appearance to all stages of human diabetic retinopathy. This animal model is extremely useful for evaluating drugs for the treatment of diabetic retinopathy; however, the time required to develop the various retinal lesions (24-72 months for background to the proliferative stage) may be considered prohibitive. Retinal vascular changes begin with an initial degeneration of capillary pericytes, which has been linked to the aldose reductase catalyzed formation of galactitol. Because aldose reductase-linked sugar cataract formation is known to be age dependent, with the onset and severity of cataract higher in younger diabetic and galactose-fed animals, retinal capillary changes in the eyes of initially 2- versus 9-month-old beagles fed a diet containing 30% galactose were compared. Eyes were enucleated after 36 months of galactose feeding, the intact retinal capillaries were isolated by trypsin digestion, and defined retinal regions were evaluated by computer image analysis. Nicotinamide adenine dinucleotide phosphate-dependent reductase activity, using DL-glyceraldehyde and D-xylose as substrates, was also compared in the lenses and whole retinas of eyes from the 2- and 9-month-old beagles. Significantly (P anterodorsal thalamus --> PoS, and terminates in the entorhinal cortex. HD cells receive multimodal information about landmarks and self-generated movements. Vestibular information appears critical for generating the directional signal, but motor/proprioceptive and landmark information are important for updating it. PMID- 17341159 TI - Peripheral regeneration. AB - Whereas the central nervous system (CNS) usually cannot regenerate, peripheral nerves regenerate spontaneously after injury because of a permissive environment and activation of the intrinsic growth capacity of neurons. Functional regeneration requires axon regrowth and remyelination of the regenerated axons by Schwann cells. Multiple factors including neurotrophic factors, extracellular matrix (ECM) proteins, and hormones participate in Schwann cell dedifferentiation, proliferation, and remyelination. We describe the current understanding of peripheral axon regeneration and focus on the molecules and potential mechanisms involved in remyelination. PMID- 17341160 TI - Association of maternal obesity before conception with poor lactation performance. AB - The objective of this review is to evaluate the evidence for a link between maternal obesity and poor lactation performance. In nonhuman species, excess maternal fatness is deleterious for lactation and also for maternal health and survival. These effects occur during pregnancy and as milk production is beginning. They may result in poor growth and survival of the young. In women, there is a negative association between maternal obesity and the initiation as well as the continuation of breastfeeding. This appears to be derived from biological as well as sociocultural factors that are still poorly understood. Excessive gestational weight gain, complications of pregnancy and delivery, and the condition of the infant at birth may also contribute to this association. Given the increasingly high rates of obesity among women of reproductive age worldwide and the importance of breastfeeding for infant health, further study of this association is essential. PMID- 17341161 TI - Self-organization and branching morphogenesis of primary salivary epithelial cells. AB - Embryonic tissues may provide clues about mechanisms required for tissue reassembly and regeneration, but few studies have utilized primary embryonic tissue to study tissue assembly. To test the capacity of tissue fragments to regenerate, we cultured fragments of embryonic day 13 (E13) mouse submandibular gland (SMG) epithelium and found that fragments as small as a quarter-bud retain the ability to branch. Further, we found that completely dissociated SMG epithelial cells self-organize into structures that undergo significant branching. Investigation into the mechanisms involved in tissue self-assembly demonstrated that inhibition of beta(1) integrin prevents cell aggregation, while inhibition of E-cadherin hinders aggregate compaction. Immunostaining showed that the cellular architecture and expression patterns of E-cadherin, beta-catenin, and actin in the reassembled aggregates mirror those seen in intact glands. Adding SMG mesenchymal cells to the epithelial cell cultures facilitates branching and morphological differentiation. Quantitative real-time RT-PCR indicated that the aggregates express the differentiation markers aquaporin-5 (AQP5), prolactin-inducible protein (PIP), and SMG protein C (SMGC). Together, these data show that dissociated SMG epithelial cells self-organize and undergo branching morphogenesis to form tissues with structural features and differentiation markers characteristic of the intact gland. These findings provide insights into self-assembly and branching that will facilitate future regeneration strategies in the salivary gland and other organs. PMID- 17341162 TI - Long-term culture of mouse vibrissal dermal papilla cells and de novo hair follicle induction. AB - We have succeeded in culturing dermal papilla (DP) cells long term and developed new techniques that enhance their hair follicle-inducing efficiency in a patch assay. The outgrowing DP cells from mouse vibrissae were markedly stimulated by 10% fetal bovine serum-Dulbecco's modified essential medium that included fibroblast growth factor-2 (FGF-2). Moreover, the potency of proliferation was maintained during serial cultivations (more than 30 passages). We combined these established DP cells with epidermal cells and implanted them subcutaneously into athymic mice to examine their hair follicle-inducing ability. New hair follicles were induced by dissociated DP cells at earlier passages (under passage 4), but the cells from later passages could not induce follicles. We next aggregated the DP cells to form spheres and then injected them with epidermal cells. Unlike the dissociated DP cells, the spheres made from the later passaged cells (more than 10 passages) did induce new hair follicles. We examined several genes specific for DP of anagen follicles and confirmed that their expression level was elevated in the spheres compared with their expression level in adherent DP cells. These results suggest that FGF-2 is essential for dermal papilla cell culture and that sphere formation partially models the intact DP, resulting in hair follicle induction, even by later passaged cells. PMID- 17341163 TI - The eyes absent family of phosphotyrosine phosphatases: properties and roles in developmental regulation of transcription. AB - Integration of multiple signaling pathways at the level of their transcriptional effectors provides an important strategy for fine-tuning gene expression and ensuring a proper program of development. Posttranslational modifications, such as phosphorylation, play important roles in modulating transcription factor activity. The discovery that the transcription factor Eyes absent (Eya) possesses protein phosphatase activity provides an interesting new paradigm. Eya may regulate the phosphorylation state of either itself or its transcriptional cofactors, thereby directly affecting transcriptional output. The identification of a growing number of transcription factors with enzymic activity suggests that such dual-function proteins exert greater control of signaling events than previously imagined. Given the conservation of both its phosphatase and transcription factor activity across mammalian species, Eya provides an excellent model for studying how a single protein integrates these two functions under the influence of multiple signaling pathways to promote development. PMID- 17341167 TI - Behavioral medicine across the lifespan. Abstracts of the 27th Annual Meeting & Scientific Sessions of the Society of Behavioral Medicine. March 22-25, 2006. San Francisco, California, USA. PMID- 17341168 TI - Neuronal and myelin reactive humoral immunity in multiple sclerosis is Th2 dependent. PMID- 17341171 TI - 5th International Congress on the Improvement of the Quality of Life on Dementia, Parkinson's disease, Epilepsy, Multiple Sclerosis and Muscular Disorders. PMID- 17341170 TI - Interferon-beta1b in multiple sclerosis. AB - In 1993, interferon (IFN)-beta(1b) for subcutaneous injection became the first US FDA-approved immunomodulatory treatment for multiple sclerosis, a chronic inflammatory disease of the CNS. In this review of IFN-beta(1b), we first present a short introduction to multiple sclerosis and currently available therapeutics. We then summarize current knowledge about the biochemical structure of IFN beta(1b), as well as pharmacokinetics and pharmacodynamics, including data on putative mechanisms underlying therapeutic as well as adverse effects. Furthermore, a critical review of ongoing and recently published clinical trials investigating IFN-beta(1b) in multiple sclerosis will be provided. Main topics are: trials investigating IFN-beta(1b) after a first clinical event, at higher dosages or in comparison to once-weekly subcutaneous IFN-beta(1a) injections, 16 years of long-term follow-up, IFN-beta(1b) in Japanese patients, the role of neutralizing antibodies, biomarkers for the prediction of therapy response, IFN beta(1b) and pregnancy, and IFN-beta(1b) treatment of children with multiple sclerosis. Finally, we discuss how novel drugs, especially monoclonal antibodies and orally administered immunosuppressants, might soon challenge the position of this well-established agent on the multiple sclerosis therapeutics market. PMID- 17341172 TI - High-altitude headache. AB - A human being's exposure to altitude, and the consequent hypobarism, entails a complex series of adaptive mechanisms that depend on the rate of ascent and the altitude reached. When these mechanisms fail, so-called acute mountain sickness (AMS) results, with headache as its predominant symptom. It has been observed, nonetheless, that well-acclimated mountaineers may have headache without symptoms of AMS. We consider that high altitude and ensuing hypobarism bring about three possibilities of cephalalgia: the first is covered by the set of AMS clinical manifestations and is undoubtedly the most frequent; the second occurs independently of acute mountain sickness and is probably due exclusively to hypoxia; and the third includes altitude-triggered migraine or migraine-like episodes. These are neurogenic problems secondary to hypoxia caused by hypobarism and, in all events, have a common denominator: hypoxia and a fundamental white organ, the brain. PMID- 17341173 TI - Use of transcranial magnetic stimulation of the brain in stroke rehabilitation. AB - Preliminary studies suggest that stimulation of the motor cortex enhances motor recovery after stroke. Most of these studies employed transcranial magnetic stimulation of the brain and two different approaches have been evaluated. The first approach is based on the use of protocols of stimulation that increase cortical excitability, targeting the hemisphere in which the stroke occurred in order to enhance the output of the motor cortex and the response to physiotherapy. The second approach is based on the use of protocols of stimulation that suppress cortical excitability, targeting the intact hemisphere in order to counteract the imbalance due to the increased interhemispheric inhibition onto the lesioned cortex, and reducing the potential negative interference of the intact hemisphere with the function of the affected one. Cumulatively, preliminary studies suggest that transcranial magnetic stimulation might be a suitable method to combine with physiotherapy and improve recovery of useful limb function in stroke patients. However, further studies are needed to determine the best stimulation parameters and how to select patients who are likely to respond to this treatment. PMID- 17341176 TI - Methods for treating cognitive deficits in schizophrenia. AB - Studies from the molecular to clinical level suggest that cognitive dysfunction is central in characterizing schizophrenia. Accordingly, there have been increased efforts to search for effective treatments of these broad and debilitating cognitive deficits. Three general strategies for treating cognitive dysfunction in schizophrenia have emerged in the literature. The second generation (atypical) antipsychotic medications have received much attention but their procognitive effects tend to be modest. Augmentation strategies, driven from basic science or translational research, have often been promising in small uncontrolled trials; however, few agents have fared well in rigorously designed trials. Behavioral interventions have demonstrated positive effects that generalize to other symptom domains and persist after the intervention, but tend to be costly and labor intensive. Thus, although there have been some exciting advances in treating cognitive dysfunction, the gains to date are modest and the search for treatment methods continues. PMID- 17341174 TI - Pharmacological treatment of bipolar disorder among children and adolescents. AB - There is growing recognition that bipolar disorder frequently first presents in adolescence. Preadolescents with volatile behavior and severe mood swings also comprise a large group of patients whose difficulties may lie within the bipolar spectrum. However, the preponderance of scientific effort and clinical trials for this condition has focused on adults. This review summarizes the complexity of bipolar disorder and diagnosis of the disease among young people. It proceeds to review the principles of pharmacotherapy, assess current treatment options and to highlight areas where evidence-based guidance is lacking. Recent developments have enlarged the range of potential treatments for bipolar disorder. Nonetheless, differences in the phenomenology, course and sequelae of bipolar disorder among young people compel greater attention to the benefits and liabilities of therapy for those affected by this illness' early onset. By summarizing current research and opinion on diagnostic issues and treatment approaches, this review aims to provide an update on a clinically important yet controversial topic. PMID- 17341175 TI - Gray and normal-appearing white matter in multiple sclerosis: an MRI perspective. AB - Besides focal white matter lesions, multiple sclerosis brain tissue also displays abnormalities in the gray matter and the normal-appearing white matter. Recent advances in magnetic resonance imaging studies of both types of tissue are discussed. Herein, normal-appearing white matter abnormalities are being found in quantitative magnetic resonance investigations, consistent with a limited degree of axonal damage and/or demyelination, and an increase of glial cells, but the specific nature of the histopathological changes underlying the quantitative magnetic resonance abnormalities remains unclear. Gray matter studies have demonstrated that much of the disease process remains undetected by conventional magnetic resonance imaging. Although newly developed techniques, such as 3D double-inversion recovery, may greatly improve detection of cortical pathology, it remains important to investigate the resultant effects on the cortical tissue alongside this, by studying integrity of normal-appearing cortical tissue through quantitative magnetic resonance studies, as well as the net neurodegenerative effect through measurements of cortical thickness and cortical atrophy (rates). To improve our understanding of normal-appearing white and gray matter changes, their mutual relations, and their relations to clinical changes, further in vivo magnetic resonance imaging studies are required. Specifically, it is proposed that more spatially specific investigations, ideally utilizing subject-specific anatomical information from, for example, diffusion fiber-tracking techniques, could be used to gain more insight into the relations between normal-appearing white matter changes, cortical changes, magnetic resonance visible focal-lesions, and physical and cognitive deficits. PMID- 17341177 TI - Women and epilepsy: review and practical recommendations. AB - Individuals with epilepsy experience a number of sex-specific problems. In women, pregnancy and delivery are obvious issues, fertility problems are more often encountered and they also seem to have a higher frequency of sexual problems. A large number of women with epilepsy experience seizure exacerbation in relation to the menstrual cycle and have higher frequencies of menstrual disturbances and polycystic ovaries. Cosmetic problems affecting skin, hair or weight may also be drug induced. The use of antiepileptic drugs may influence the effect of contraceptives leading to unplanned pregnancies and contraceptives may affect the serum levels of antiepileptic drugs. The care of pregnant women with epilepsy requires attention to a number of guidelines and close cooperation between neurologist and gynecologist is recommended. Although the majority of the women with epilepsy experience normal pregnancies and deliveries, their children have a higher risk of birth defects. At menopause, their seizure pattern may change and some antiepileptic drugs may increase the risk of osteoporosis. The optimal treatment of women with epilepsy should take into account these gender-specific issues in the different stages of life. PMID- 17341178 TI - Prostatitis and chronic prostatitis/chronic pelvic pain syndrome. AB - The prevalence of prostatitis is extremely high, with up to 16% of men diagnosed with prostatitis at some point throughout their lifetime. However, the etiology appears to be multifactorial and standard treatment regimens have been altered significantly in recent years. The purpose of this review is to examine the changing scientific views on the causes and treatment of prostatitis, chronic prostaitis and chronic pelvic pain syndrome. We review the infectious and noninfectious etiology of the disease, examining the role of antimicrobial treatment in eradicating infection as well as ameliorating symptoms. Current NIH classifications, which stratify prostatitis into four categories, are discussed, as is the NIH Chronic Prostatitis Symptom Index, the primary tool used to assess symptomatology. Diagnostic examinations are studying the need for the four-glass test and its practical replacement by the two-glass test. Multimodal treatment therapy is then discussed, including recent data on biofeedback and evaluation of the role of pelvic floor dysfunction in prostatitis. PMID- 17341180 TI - Calcium signaling in ocular arterioles. AB - Local control of blood flow to the photoreceptors and associated neurons in the retina is largely achieved through changes in tone within the choroidal and retinal arterioles. This is primarily achieved through changes in [Ca2+] within the smooth muscle of these vessels, which regulates cell contraction and vascular constriction. Here we review some aspects of the cell physiology involved in these Ca2+-signaling processes, with particular emphasis on the molecular mechanisms involved. Ca2+-influx across the plasma membrane can occur via a variety of Ca2+-channels, including voltage-operated, store-operated, and receptor-operated channels. Ca2+ may also be released from intracellular stores via RyR-, or IP3R-gated channels in the SR membrane. Using high-speed confocal Ca2+-imaging, we have also demonstrated that the resulting signals are far from homogeneous, with spontaneous activity in retinal arterioles being characterized by both localized Ca2+-sparks and more global Ca2+-waves and oscillations. These signals may be specifically and differentially targeted, for example, to Ca2+ sensitive ion channels (stimulus-excitation coupling), or pathways regulating contraction (stimulus-contraction coupling). Exploring the role of changes in such targeting in disease states will provide exciting opportunities for future research. PMID- 17341182 TI - Membrane receptors for vitamin D metabolites. AB - Membrane-initiated signaling by steroid hormones is now widely accepted. Current debate is centered upon which protein moieties act as membrane-associated receptors. In this review, we consider evidence for the classical vitamin D receptor (VDR) in this role, as well as the more recently identified 1,25D3-MARRS (membrane-associated, rapid response steroid binding) receptor, also known as ERp57/GRp58. The structure of the 1,25D3-MARRS receptor is discussed, with emphasis on two thioredoxin domains that promote dimerization and ligand binding. We then summarize recent studies on a 24,25(OH)2D3 binding protein--catalase--and how ligand-induced decreases in enzymatic activity produce increased reactive oxygen species that target both the 1,25D3-MARRS receptor--but not the VDR--and the protein kinase C signaling pathway. Finally, we briefly discuss the available literature suggesting that the metabolite 25(OH)D3 may also be biologically active. PMID- 17341183 TI - Protein tyrosine phosphatases in osteoclasts. AB - Osteoclasts are large cells derived from the monocyte-macrophage hematopoietic cell lineage, whose primary function is to degrade bone in various physiological contexts. Reversible phosphorylation of tyrosine residues in proteins is known to play significant roles in regulating the function of osteoclasts, much as it does in other cell types. Protein tyrosine phosphatases (PTPs) are among the major regulators of this process, but significant gaps exist in our knowledge of which phosphatases function in osteoclasts and the nature of their precise cellular and molecular roles. We review here the roles of the four tyrosine phosphatases that are known currently to be expressed in osteoclasts--PTPRO, PTP epsilon (PTPepsilon), SHP-1, and PTP-PEST. Of these, PTPRO and PTPepsilon support osteoclast activity, whereas SHP-1 inhibits it. Much future research is required to uncover additional PTPs that function in osteoclasts and provide full molecular-level accounting of their respective roles in osteoclasts. PMID- 17341184 TI - Heavy-chain-only antibody expression and B-cell development in the mouse. AB - Antibodies expressed in mice, humans, and most mammals consist of paired heavy (H) and light (L) chains. Cellular release of single H-chains without L-chains is prevented by chaperone association and retention in the endoplasmic reticulum. Consequently, H-chain-only antibodies are absent, except in pathological conditions known as Heavy Chain Disease, where they occur in mutated form. An exception to this is found in the serum of Camelidae. Homodimeric H-chain antibodies in camelids lack the first constant region domain (CH1) of the H-chain but retain an otherwise intact H-chain polypeptide, thus maintaining antigen specificity and effector functions. In this review, we summarize how H-chain antibodies can be expressed in mice, and whether normal developmental processes leading to antibody expression without L-chain are retained. PMID- 17341185 TI - Structure and function of cas-L and integrin-mediated signaling. AB - Cas-L (Crk-associated substrate lymphocyte type), also known as HEF1 (human enhancer of filamentation 1) or NEDD9 (neural precursor cell-expressed, developmentally downregulated gene 9), is an adapter protein at focal adhesions and transmits various signals, mainly induced by integrins. Cas-L is a member of the Cas family proteins and is expressed preferentially in lymphocytes and epithelial cells. A number of previous studies have suggested that Cas-L plays an important role in lymphocyte movement and cell cycle. Recently, we reported a novel function of Cas-L in the immune system using gene-targeted mice. The Cas-L deficient lymphocytes showed insufficient chemotactic response and perturbed cell adhesion. Moreover, a deficit of marginal zone (MZ) B cells was detected in the mutant mice. Here, we review the structure of Cas-L and several signaling pathways in which Cas-L is involved, based on the previous in vitro studies. Subsequently, biological functions of Cas-L and the relevance of Cas-L to human diseases are discussed. PMID- 17341186 TI - Host immune responses to the intracellular bacteria Brucella: does the bacteria instruct the host to facilitate chronic infection? AB - Brucella spp. are intracellular gram-negative bacteria that include a number of virulent species that cause chronic infections in a variety of mammalian hosts. Human infections are proportional to the level of disease in domestic animals because humans are infected zoonotically after contact with infected animals or their products. The chronicity of infection results from the ability of some brucellae to survive reactive oxygen intermediate and nitric oxide killing in host phagocytes, following which they activate bacterial genes in response to the acidic phagosome environment, prevent phagolysosomal fusion by remodeling the intracellular compartment, and subsequently replicate intracellularly. The crucial component of immunity that results in survival of the host and thus maintenance of this chronic infective state is interferon-gamma (IFN-gamma). Production of IFN-gamma results from the ability of brucella components, including lipid A, to interact with Toll-like receptors for the production of IL 12 and TNF-alpha, although the regulatory cytokine IL-10 is also produced and decreases control of the infection. Although CD4 and CD8 T cells are clearly involved in the production of IFN-gamma, and CD8 T cells may be cytotoxic, a role for NK cells and cytotoxicity in protective immunity to brucellosis has not been substantiated experimentally. Moreover, antibodies have been shown to have a limited role in passive transfer studies. PMID- 17341181 TI - Reflections on lineage potential of skeletal muscle satellite cells: do they sometimes go MAD? AB - Postnatal muscle growth and repair is supported by satellite cells--myogenic progenitors positioned between the myofiber basal lamina and plasma membrane. In adult muscles, satellite cells are quiescent but become activated and contribute differentiated progeny when myofiber repair is needed. The development of cells expressing osteogenic and adipogenic genes alongside myoblasts in myofiber cultures raised the hypothesis that satellite cells possess mesenchymal plasticity. Clonal studies of myofiber-associated cells further suggest that satellite cell myogeneity and diversion into Mesenchymal Alternative Differentiation (MAD) occur in vitro by a stochastic mechanism. However, in vivo this potential may be executed only when myogenic signals are impaired and the muscle tissue is compromised. Such a mechanism may contribute to the increased adiposity of aging muscles. Alternatively, it is possible that mesenchymal interstitial cells (sometimes co-isolated with myofibers), rather than satellite cells, account for the nonmyogenic cells observed in myogenic cultures. Herein, we first elaborate on the myogenic potential of satellite cells. We then introduce definitions of adult stem-cell unipotency, multipotency, and plasticity, as well as elaborate on recent studies that established the status of satellite cells as myogenic stem cells. Last, we highlight evidence in favor of satellite cell plasticity and emerging hurdles restraining this hypothesis. PMID- 17341187 TI - Role of cAMP phosphodiesterase 4 in regulation of T-cell function. AB - Ligation of both the T-cell receptor (TCR) and the CD28 receptor is required for full T-cell activation to occur. Engagement of the TCR in primary T cells is followed by rapid cAMP production in lipid rafts resulting in raft-associated protein kinase A (PKA) activation and inhibition of proximal T-cell signaling. However, upon TCR and CD28 cross-ligation, beta-arrestin in complex with cAMP specific phosphodiesterase 4 (PDE4) is recruited to lipid rafts, thus downregulating cAMP levels. Consequently, the activities of both PKA and PDE4 seem to be important for the regulation of TCR-induced signaling and T-cell function. We, therefore, propose a novel role for TCR and CD28 co-stimulation in the downmodulation of TCR-induced cAMP-mediated inhibitory signals through the recruitment of beta-arrestin and PDE4 to lipid rafts, thus allowing a full T-cell response to occur. PMID- 17341188 TI - The role of NKT cells in animal models of autoimmune hepatitis. AB - NKT cells expressing invariant T-cell receptors are an abundant cell population in the mouse liver, and much evidence has been accumulating which shows that they play an important role in immune responses in this organ. In this review, the putative function of NKT cells in autoimmune hepatitis is discussed based on results from various mouse models. Features and functions of invariant NKT cells are summarized to set the stage to explain how these cells induce liver injury following the injection of mitogen concanavalin A or NKT-cell receptor ligand alpha-GalCer. Results are discussed which show that alcohol consumption can aggravate liver injury by NKT cells, whereas expression of a hepatitis C virus protein in hepatocytes can protect against injury. Hepatocytes, therefore, can modulate sensitivity to NKT-cell-mediated attack. Moreover, experiments that elucidate how NKT cells induce liver injury and how they are regulated to perform this function are discussed. Specific attention is given to the recently discovered role of purinergic receptor P2X7 in regulating NKT cells. The conclusion is drawn that the P2X7 receptor constitutes a sensor that senses purine-based danger signals, which trigger mechanisms that cause inhibition or stimulation of NKT-cell functions. PMID- 17341189 TI - Regulation of thymocyte survival by transcriptional coactivators. AB - A majority of the developing T cells are eliminated by apoptosis because they do not meet the positive and negative selection criteria. Developing T cells are thus susceptible to apoptotic signals. On the other hand, there are mechanisms to prevent developing T cells from premature apoptosis. Maintenance of a fine balance between life and death is thus critical for successful completion of T cell development. Our recent studies demonstrated an essential role of transcriptional coactivators in maintaining such a balance for developing T cells. Transcriptional coactivators are recruited by transcriptional factors to quantitatively regulate gene expression via modifying chromatin structure. Two transcriptional factors, TCF-1 and ROR gamma t, are required to upregulate the levels of Bcl-xL, a critical survival factor for CD4+CD8+ double-positive thymocytes. However, TCF-1 and ROR gamma t by themselves are not sufficient to stimulate Bcl-xL expression. Transcriptional coactivator beta-catenin recruited by TCF-1, and steroid receptor coactivators (SRCs) recruited by ROR gamma t, are also required for optimal stimulation of Bcl-xL expression. Thus, transcriptional coactivators are a substantial component of the transcriptional machinery to regulate thymocye survival, ensuring the completion of T-cell development. PMID- 17341190 TI - The proteasome and its inhibitors in immune regulation and immune disorders. AB - The ubiquitin-proteasome pathway is a well-characterized mechanism deputed to the degradation of intracellular proteins. Proteasomal degradation intervenes in the regulation of numerous cellular functions including signal transduction, apoptosis, cell cycle, and antigen presentation. In vitro and in vivo studies have shown that both normal and malignant cells of the immune system are exquisitely affected by inhibition of proteasome activity. This property is currently exploited in the treatment of multiple myeloma and mantle cell lymphoma, two B-cell malignancies that respond to treatment with the proteasome inhibitor bortezomib. Pharmacological inhibitors of the proteasome also affect function and survival of B and T lymphocytes and of dendritic cells and were shown to reduce autoimmune and inflammatory manifestations in several models of immune-mediated disorders. The present review offers an overview of the mechanisms implicated in the immunomodulatory effects of proteasome inhibitors and discusses prospective future applications for these small molecules in immune and inflammatory diseases. PMID- 17341191 TI - Regulation of immune response by P2X7 receptor. AB - The P2X7 receptor is an ATP-gated cation channel that is widely expressed in cells of the immune system. Signal transduction is accompanied by fast influx of Ca2+ and Na+, and efflux of K+. This receptor differs from other members of the P2X family in its relatively low affinity for ATP, the presence of a long C terminal region that contains several protein-protein interaction motifs, and the activation of two membrane conductance states following receptor ligation. In the immune system, this receptor has been implicated in the processing and release of cytokines such as IL-1 beta, and in the initiation of cell death via both apoptotic and necrotic pathways. As such, it has been proposed to function as a major regulator of inflammation. Consistent with this hypothesis, inactivation of this receptor in mice modulates disease pathogenesis in several animal models of inflammatory and autoimmune diseases. Loss-of-function polymorphisms have also been noted in the human population, and there is accumulating evidence that these polymorphisms are linked to certain diseases. In this article, we review the current status of research in this field, with particular emphasis on the signaling pathways activated by this receptor, the mechanisms involved in the initiation of cell death, and associations with disease states in mice and humans. PMID- 17341192 TI - Immunological protection against mycobacterium tuberculosis infection. AB - Mycobacterium tuberculosis (Mtb) invades the lung via an airborne pathway, and the bacteria reach the lung alveoli and are then engulfed by alveolar macrophages in innate immunity, which uses germline-encoded pattern recognition receptors such as the mannose receptor and Toll-like receptor for recognition of the pathogen. Mtb can survive in phagosomes of macrophages by escaping from lysosomal enzyme and reactive nitrogen intermediate toxicity. Dendritic cells transport Mtb from lung mucosa to draining lymph nodes and present the mycobacterial antigens to CD4+ and CD8+ T cells in adaptive immunity, which uses antigen-specific receptors formed by somatic gene rearrangement. Natural memory T cells such as gammadelta T cells and CD 1-restricted T cells are also stimulated and serve to shape the subsequent development of T-helper 1-dominant immunity, which induces granuloma at the initial focus of infection, is sufficient to prevent acute tuberculosis, but is unable to eradicate the infection completely. Once the host's defense becomes compromised, reactivation of the disease, which is called latent infection with Mtb, occurs. Recent progress in elucidating adaptive immune responses to acute and latent infection with Mtb may lead to the establishment of effective therapeutic and prophylactic approaches for controlling Mtb infection. PMID- 17341193 TI - DNA motifs suppressing TLR9 responses. AB - Immune cells respond to bacterial DNA containing unmethylated CpG motifs via Toll like receptor 9 (TLR9). Given the apparent role of TLR9 in development of systemic lupus erythematosus (SLE), there is interest in the development of TLR9 inhibitors. TLR9-mediated responses are reported to be inhibited by a confusing variety of different DNA sequences and structures. To aid characterization, we have provisionally categorized TLR9-inhibitory oligodeoxynucleotides (ODN) into 4 classes, on the basis of sequence and probable mode of action. Class I are short G-rich ODN, which show sequence-specific inhibition of all TLR9 responses, and may be direct competitive inhibitors for DNA binding to TLR9. Class II are telomeric repeat motifs that inhibit STAT signaling, and thus are not specific to TLR9 responses. Because Class II ODN are generally made as 24-base phosphorothioate-modified ODN (PS-ODN), they also fall into Class IV, defined as long PS-ODN, which inhibit TLR9 responses in a sequence-nonspecific manner. Class III includes oligo (dG) that forms a 4-stranded structure and inhibits DNA uptake. The Class I G-rich motifs show the most promise as selective and potent TLR9 inhibitors for therapeutic applications. PMID- 17341194 TI - Human defensins and cathelicidins in the skin: beyond direct antimicrobial properties. AB - A cutaneous barrier defends the body against invading pathogenic microorganisms due to both innate and adaptive immunity. The innate immune system comprises hundreds of peptides/proteins, which have potent microbicidal activities at low concentrations. Among these microbicidal agents, an increasing body of research has suggested that a vast arsenal of antimicrobial peptides composed of defensins and cathelicidins are key players in cutaneous immunity. Mainly produced by phagocytes and epithelial cells, defensins and cathelicidins directly or indirectly kill a wide range of bacteria, fungi, and viruses. However, it is increasingly evident that these peptides not only act as endogenous antibiotics but also display additional roles, such as regulation of inflammatory and immune responses, chemoattracting immune or inflammatory cells to wound or infection/inflammation sites, acceleration of angiogenesis, promotion of wound healing, and reepithelization, and binding and neutralizing of lipopolysaccharides. Here, we review the skin-derived antimicrobial peptides with an emphasis on their role in skin immune responses. We present an overview of defensin and cathelicidin structure and expression, clarify their various functions beyond microbicidal properties, and describe their modes of action. Moreover, we discuss the roles of these peptides in skin diseases and highlight their possible use in near therapeutic development. PMID- 17341196 TI - Microfluidic techniques for studying the nervous system. AB - Recent advances in micro- and nano-fabrication techniques have led to the development of microfluidic platforms designed for in vitro biological studies. Based on their capability of precise control of the environment surrounding individual cells, these microfluidic platforms have been increasingly utilized to investigate physiologic responses at the single-cell level. It is likely that these devices will continue to gain popularity as a tool to study the behavior of individual cells as they are exposed to extrinsic agents and other cells. This article reviews microfluidic technology and its application to single-cell research, with emphasis on advances that are particularly useful for neuronal studies, such as platforms with patterned physical and chemical cues, integrated electrophysiology and other sensors, architecture for isolation of axons, and delivery of precisely controlled chemical factors. PMID- 17341197 TI - Auditory hypergnosia as an example of psychic tonus in the temporal lobes: multiple case analyses. AB - In 2006, Braun proposed a new model of hemispheric specialization of energy management by the brain, which he termed the "psychic tonus" model of hemispheric specialization. The term "psychic tonus" is deliberately general. It invites further investigation designed to incorporate various behavioral and cognitive modalities. At present, any cognitive operation or behavior likely to require energy expenditure, such as cardiovascular or metabolic, is considered to be at one extreme while any cognitive operation or behavior likely to reduce energy expenditure is considered to be at the other extreme. The model states that the left hemisphere of the brain is specialized to increase psychic tonus and the right to decrease it. The model predicts that the tonus of auditory representation ought to also manifest these hemispheric specializations in the temporal lobes. Specifically, it was predicted that pathological positive auditory tonus (auditory hallucination) ought to be associated more frequently with right temporal lobe lesions. Our analysis of a large number of previously published cases of patients with unilateral lesions supports the prediction. PMID- 17341198 TI - Acetylcholine release from the central nervous system: a 50-year retrospective. AB - Some 50 years have elapsed since Elliot et al. and MacIntosh & Oborin first reported a release of acetylcholine (ACh) from canine and feline cerebral cortices, respectively. In this review, subsequent developments in the field during the succeeding five decades are explored. The arrangement of material in the review is outlined in this abstract, concluding with some suggestions as to its potential significance. A number of technical advances during this period have contributed to a greater understanding of the role that ACh may play in the central nervous system. These include the relatively recent evolution of the microdialysis and transverse dialysis techniques that enabled investigators to explore ACh release in deep regions of the brain. Future studies will likely be refined with the use of microelectrode biosensors, which should allow real-time measurements of ACh concentrations at the synaptic level. Controversies arising from the use of cholinesterase inhibitors and muscarinic receptor antagonists to enhance release are being resolved as a result of a better understanding of the presynaptic actions of these agents. Future studies will also benefit from the recent development of clostridial and other neurotoxins to reduce ACh release in areas of the brain. The likelihood that ACh may act as a cotransmitter at synapses in conjunction with glutamic acid, nitric oxide, and adenosine triphosphate is also explored. Attention is focused on the elucidation of choline acetyl-transferase (ChAT)-containing pathways in the central nervous system using techniques such as immunohistochemistry, in situ hybridization, histochemistry of ChAT mRNA, acetylcholinesterase histochemistry, and the distribution of the vesicular ACh transporter. Such studies have defined several major groupings of cholinergic neurons in the brain, which provide ascending or descending projections to higher and lower central structures. A major section of the review is devoted to actual studies on ACh release in the brain and spinal cord. This presentation is in two sections. The text details some of the material that has been obtained in experiments over the past 50 years. In five Tables, the results obtained in the majority of release studies to date are summarized. Although the data obtained to date clearly support the hypothesis that ACh is involved in electroencephalographic activation associated with cerebral cortical arousal, this occurs while the animals appear to be awake with full postural control, suggesting that noncholinergic pathways to the cerebral cortex are also involved in such behavioral manifestations. The roles of acetylcholine in cognitive processes such as attention, learning, memory, responses to environmental changes, and motor activity still remain to be defined. PMID- 17341200 TI - Functional polymeric nanoparticles: an efficient and promising tool for active delivery of bioactives. AB - Nanotechnology is a multidisciplinary field and has achieved breakthroughs in bioengineering, molecular biology, diagnostics, and therapeutics. A recent advance in nanotechnology is the development of a functional nanosystem by incorporation, adsorption, or covalent coupling of polymers, carbohydrates, endogenous substances/ligands, peptides, proteins, nucleic acids, and polysaccharides to the surface of nanoparticles. Functionalization confers a wide array of interesting properties such as stealth characteristics, a bioadhesive property, and that it prevents aggregation of nanoparticles, imparts biostability and solubility, reduces toxicity, and provides site-specific delivery. This makes the nanosystem an intelligent tool for diagnostics, prognostics, and controlled and sustained delivery of protein, peptide, pDNA, and other therapeutic agents to specific targets (tissue, cell, and intracellular). Various types of functional nanosystems, such as carbon nanotubes, quantum dots, polymeric micelles, dendrimers, metallic nanoparticles, and liposomes, are being extensively explored. However, high tissue accumulation of nonbiodegradable nanoparticles has caused toxicity problems and rendered them as not-so-popular therapeutic and diagnostic systems. The toxicity and safety of nonbiodegradable nanoparticles are subject to future research. Polymeric nanoparticles have offered attractive alternative modules due to biocompatibility, nonimmunogenicity, nontoxicity, biodegradability, simple preparation methods, high physical stability, possibility of sustained drug release, and higher probability for surface functionalization. Depending on properties that have been modified, polymeric nanoparticles can be grouped in to four classes, namely, stealth, polysaccharide decorated biomimetic, bioadhesive, and ligand-anchored functional polymeric nanoparticles (f-PNPs). This review explores the ligand-anchored f-PNP as a carrier for active delivery of bioactives, envisaged to date. This review also details the ligands available for conjugation, their method of coupling to nanoparticles, and applications of f-PNPs in anticancer drug delivery, oral delivery, gene delivery, vaccine delivery, and intracellular delivery; site specific delivery to liver, macrophages, lymphatics, and brain; and miscellaneous applications. This review also addresses formidable challenges encountered, and proposes some future strategies for development of a promising site-specific active delivery system. PMID- 17341201 TI - Formulation and physiological factors influencing CNS delivery upon intranasal administration. AB - The treatment of central nervous system (CNS) disorders is particularly challenging because of a variety of formidable barriers to effective and persistent delivery of therapeutic compounds. This review discusses the potential of intranasal drug administration as a means to bypass a major barrier, the blood brain barrier, and allow for direct delivery of drugs into the CNS. The article emphasizes physicochemical properties of intranasal drug formulations as well as relevant anatomical and physiological factors in intranasal delivery of drugs for CNS therapy. Published examples of intranasal administration of small molecular weight drugs, peptides and proteins, and novel formulations for delivering a broad spectrum of molecules are discussed. Finally, the article provides several strategies for effectively enhancing nose-to-brain transport of drug molecules through rational formulation design and optimization. PMID- 17341202 TI - Effects of Aegle marmelos (L.) Correa on the peripheral blood and small intestine of mice exposed to gamma radiation. AB - The radioprotective effect of bael (Aegle marmelos, AME) extract was studied in Swiss albino mice against radiation-induced changes in the peripheral blood, spleen colony forming units, and intestinal mucosa. The mice were treated with 250 mg/kg body weight of AME orally once daily for five consecutive days before exposure to an acute dose of 7 Gy of gamma radiation after the last administration. The peripheral blood was collected and evaluated for red blood cell (RBC), hemoglobin, total leukocyte count (TLC), and lymphocyte count on days one and seven postirradiation. The nucleated bone marrow cells were isolated and tested for colony-forming units (CFUs) in spleen at days one and seven. AME protected mice against the radiation-induced decline in hemoglobin, total leukocyte, and lymphocytes counts and the clonogenicity of hemopoietic progenitor cells assessed by the exogenous spleen colony-forming assay. Irradiation of mice caused a significant decline in the villus height and crypt number with an increase in goblet and dead cells in the small intestine, where the maximum changes were observed on day one postirradiation, indicating a severe damage, and signs of recovery at day seven postirradiation. Treatment of mice with AME before irradiation elevated the peripheral cell count as well as villus height and the crypt number accompanied by a decline in goblet and dead cells when compared with the irradiation control. The recovery and regeneration were faster in AME pretreated animals than the irradiation alone. AME pretreatment significantly decreased lipid peroxidation accompanied by a significant elevation in the GSH concentration in the mouse intestine. The data clearly indicate that the AME significantly reduced the deleterious effect of radiation in the intestine and bone marrow of mouse and could be a useful agent in reducing the side effects of therapeutic radiation. PMID- 17341203 TI - Electroporation enhances radiation and doxorubicin-induced toxicity in solid tumor in vivo. AB - Treatment of cancer patients is subject to limitations in radiotherapy and chemotherapy. This necessitates development of new protocols, and the present work reports on the effects of a combination of local electroporation with ionizing radiation and/or anticancer drug doxorubicin hydrochloride (DOX) on subcutaneous solid tumor murine fibrosarcoma. Localized treatment of fibrosarcoma tumor, grown in right hind leg of Swiss mice, has been carried out using DOX (0.6 mg/kg body weight), radiation (Co 60 gamma-rays, dose rate 0.37 Gy/min) and electroporation (1 kV/cm, 200 micros, 8 pulses per burst, 10 bursts) individually or in combinations. Measurements of the tumor growth kinetics after treatment with combinations have revealed significant growth delay. The treatment groups, (i) radiation and electroporation, (ii) DOX and electroporation, and (iii) radiation, DOX and electroporation, have yielded tumor growth delays (TGDs) of 1.22, 1.5, and 1.73 days, respectively, compared to control with the tumor volumes being 53%, 57%, and 49% that of control on the final day of observation. These results suggest that the antitumor effects of a moderate dose of gamma radiation and low concentration of DOX can be significantly enhanced by combination with electroporation. PMID- 17341204 TI - Radioprotective potential of Rosemarinus officinalis against lethal effects of gamma radiation : a preliminary study. AB - The radioprotective effect of Rosemarinus officinalis extract (ROE) was studied in mice exposed to 8 Gy of gamma radiation. The optimum dose for radioprotection was determined by administering 100, 200, 400, 800, 1000, 1500, and 2000 mg/kg body weight of ROE orally once daily, consecutively for five days before irradiation. Treatment of mice with ROE, delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. The dose of ROE found to be most effective against radiation was 1000 mg/kg body weight because this dose increased the survival time and reduced the mortality rate of mice significantly. Body weight loss in ROE administered irradiated animals was significantly less in comparison with animals who were given radiation treatment alone. Furthermore, irradiation of animals resulted in an elevation in lipid peroxidation (LPx) and a significant decrease in glutathione (GSH) in blood and liver. Conversely, administration of animals with ROE before irradiation caused a significant decline in LPx accompanied by a significant increase in GSH concentration. The present study demonstrates that Rosemarinus officinalis leave extract is a good radioprotector. PMID- 17341205 TI - Emblica officinalis (Linn.) fruit extract provides protection against radiation induced hematological and biochemical alterations in mice. AB - Oral administration of Emblica officinalis (Linn.) before exposure to gamma radiation was found to be effective in protecting mice against the hematological and biochemical modulation in peripheral blood. A significant increase in the RBC, WBC, hemoglobin, and hematocrit values was observed in the animals pretreated with E. officinalis extract as compared to the hematological values observed in the irradiated group. Furthermore, radiation sickness was greatly inhibited in those mice that were irradiated with prior treatment of E. officinalis. A significant decrease in glutathione (GSH) content and increase in lipid peroxidation (LPx) level were also observed in irradiated animals; whereas E. officinalis pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPx level, but such remained below the normal. The results from the present study suggest that E. officinalis pretreatment provides protection against irradiation to Swiss albino mice. PMID- 17341206 TI - Cell membrane-associated MT1-MMP dependent activation of MMP-2 in SiHa (human cervical cancer) cells. AB - Among the soluble MMPs, MMP-2 (gelatinase A) is particularly important in the invasive property of tumor cells. Cell membrane-associated MMP-2 activation is one of the challenging areas in tumor biology. In the present communication, we studied the membrane dependent activation of MMP-2 in SiHa cells. METHODS: Activation of pro-MMP-2 by membrane fraction, membrane extract, and live SiHa cells was studied by gelatin zymography. The role of MT1-MMP in MMP-2 activation was studied by incubating SiHa cells and cell membrane fractions with anti-MT1 MMP antibody. RESULTS: Activation of purified pro-MMP-2 by membrane fraction isolated from SiHa cells, by SiHa cell membrane extract and by SiHa cells, pro MMP-2 from Con A treated HT-1080 conditioned medium by SiHa cells, and pro-MMP-2 from serum free culture medium of SiHa cells and cervical tissue homogenate by SiHa cell membrane fraction was shown by gelatin zymography. SiHa membrane fraction activated only pro-MMP-2 from purified MMP-9/MMP-2 mixture, indicating that the activation is specific for MMP-2. Inhibition of MMP-2 activation in the presence of anti-MT1-MMP antibody strongly indicated that the cell membrane mediated MMP-2 activation is MT1-MMP dependent. Immunocytochemistry of SiHa cells demonstrated expression of MT1-MMP at focal points. Invasion assay showed that invasiveness of anti-MT1-MMP antibody treated SiHa cells through Matrigel was drastically reduced compared to control SiHa cells. CONCLUSIONS: Our findings furnish an example of the cell membrane-associated MT1-MMP mediated MMP-2 activation in SiHa cells and suggest that this MT1-MMP mediated MMP-2 activation is of importance in tumor invasion and metastasis. This MT1-MMP mediated MMP-2 activation on tumor cell surface could be a realistic target for managing metastatic diseases. PMID- 17341207 TI - Culture of human fibrosarcoma HT-1080 cells in presence of fibronectin activates MMP-2. AB - The importance of tumor cell surface integrin receptors in regulation of matrix metalloproteinase (MMP) expression and function has been reported. Integrin-ECM ligand interaction leads to phosphorylation of focal adhesion kinase (FAK) and activation of mitogen activated protein kinase (MAPK) pathways. In this present study, we cultured human fibrosarcoma cells, HT-1080, in presence of fibronectin to study fibronectin-integrin mediated modulation of MMP activity. METHODS: HT 1080 cells were cultured in serum free medium (SFCM) in presence of fibronectin, SFCM was collected, and gelatin zymography was performed. Western blot and immunocytochemistry were performed with HT-1080 cells cultured in presence of fibronectin. RESULTS: Culture of HT-1080 cells in presence of 50 microg/1.5 ml fibronectin led to expression of pro-MMP-9 and activation of MMP-2 within 1 hr. When HT-1080 cells were treated with PI-3K inhibitor (LY294002) and grown in presence of fibronectin, MMP-2 activation was partially inhibited, but when cells were treated with ERK inhibitor (PD98059) and grown in presence of fibronectin, MMP-2 activation was almost completely inhibited. Tyrosine phosphorylation of FAK and ERK were increased in HT-1080 cells grown in presence of fibronectin. Processing of MT1-MMP was also observed in HT-1080 cells grown in presence of fibronectin. The reorganization of actin filaments in fibronectin treated HT-1080 cells was also noticeable. CONCLUSIONS: Our findings indicate that culture of HT 1080 cells in SFCM in presence of fibronectin perhaps generates a signaling cascade that leads to expression of pro-MMP-9 and activation of MMP-2 within 1 hr. The signaling pathway activated seems to be the FAK/ERK pathway. PMID- 17341208 TI - Curcumin, a potential inhibitor of MMP-2 in human laryngeal squamous carcinoma cells HEp2. AB - Curcumin (diferuloylmethane) has been widely studied for its tumor inhibiting and anticarcino-genic properties. In the present communication, we studied the effect of curcumin on matrix-metalloproteinase-2 (MMP-2), integrin receptors, and focal adhesion kinase (FAK) in human laryngeal cancer cells, HEp2. METHODS: HEp2 cells were treated with curcumin (5 microM) for 30 days and then grown without curcumin for 28 days. Effect of curcumin on MMP-2 expression and activity and on membrane type matrixmetalloproteinase-1 (MT1-MMP), FAK, and integrin receptors was studied by zymography, Western blot, ELISA, RT-PCR, and cell adhesion assay. RESULTS: Treatment of HEp2 cells with curcumin downregulated MMP-2 expression and activity and expression of integrin receptors, FAK, and MT1-MMP to almost background levels. MMP-2 (but not MMP-9) mRNA expression was abolished on curcumin treatment, indicating specific inhibition of MMP-2. Invasive potential of HEp2 cells was also significantly reduced. After drug withdrawal, expression of MMP-2, integrin receptors, MT1-MMP, and FAK returned to control levels. However, MMP-2 activity in serum free medium remained low. CONCLUSIONS: Downregulation of integrin receptors and low levels of FAK may hinder integrin-mediated signal transduction, preventing upregulation of MMP-2 activity. Reduction of MMP-2 activity and inhibition of HEp2 cell invasion by curcumin strongly indicate the potential of curcumin as an inhibitor of tumor cell invasion and metastasis. PMID- 17341211 TI - WITHDRAWN:Structurally reduced monosaccharide transporters in an evolutionary conserved red alga. AB - The paper entitled "Structurally reduced monosaccharide transporters in an evolutionary conserved red alga", which was published online on 7 March 2007, was withdrawn at the author's request. PMID- 17341210 TI - The mechanism of addition of pyridoxal 5'-phosphate to Escherichia coli apo serine hydroxymethyltransferase. AB - Previous studies suggest that the addition of pyridoxal 5'-phosphate to apo serine hydroxymethyltransferase from Escherichia coli is the last event in the enzyme's folding process. We propose a mechanism for this reaction based on quenched-flow, stopped-flow and rapid-scanning stopped-flow experiments. All experiments were performed with an excess of apo-enzyme over cofactor, since excess pyridoxal 5'-phosphate results in a second molecule of cofactor binding to Lys346, which is part of the tetrahydropteroylglutamate-binding site. The equilibrium between the aldehyde and hydrate forms of the cofactor affects the kinetics of addition to the active site. Direct evidence of the formation of an intermediate aldimine between the cofactor and the active-site lysine was obtained. The results have been interpreted according to a three-step mechanism in which: (i) both aldehyde and hydrate forms of the cofactor bind rapidly and non-covalently to the apo-enzyme; (ii) only the aldehyde form reacts with the active-site lysine to give an intermediate internal aldimine with unusual spectral properties; and (iii) a final conformational change gives the native holo-enzyme. PMID- 17341213 TI - Introduction: moving forward the discussion on childhood obesity. PMID- 17341212 TI - Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP activated protein kinase (AMPK). AB - The renal-specific NKCC2 (Na+-K+-2Cl- co-transporter 2) is regulated by changes in phosphorylation state, however, the phosphorylation sites and kinases responsible have not been fully elucidated. In the present study, we demonstrate that the metabolic sensing kinase AMPK (AMP-activated protein kinase) phosphorylates NKCC2 on Ser126 in vitro. Co-precipitation experiments indicated that there is a physical association between AMPK and the N-terminal cytoplasmic domain of NKCC2. Activation of AMPK in the MMDD1 (mouse macula densa-derived 1) cell line resulted in an increase in Ser126 phosphorylation in situ, suggesting that AMPK may phosphorylate NKCC2 in vivo. The functional significance of Ser126 phosphorylation was examined by mutating the serine residue to an alanine residue resulting in a marked reduction in co-transporter activity when exogenously expressed in Xenopus laevis oocytes under isotonic conditions. Under hypertonic conditions no significant change of activity was observed. Therefore the present study identifies a novel phosphorylation site that maintains NKCC2-mediated transport under isotonic or basal conditions. Moreover, the metabolic-sensing kinase, AMPK, is able to phosphorylate this site, potentially linking the cellular energy state with changes in co-transporter activity. PMID- 17341214 TI - From tastes great to cool: children's food marketing and the rise of the symbolic. AB - Children's exposure to food marketing has exploded in recent years, along with rates of obesity and overweight. Children of color and low-income children are disproportionately at risk for both marketing exposure and becoming overweight. Comprehensive reviews of the literature show that advertising is effective in changing children's food preferences and diets. This paper surveys the scope and scale of current marketing practices, and focuses on the growing use of symbolic appeals that are central in food brands to themes such as finding an identity and feeling powerful and in control. These themes are so potent because they are central to children in their development and constitution of self. The paper concludes that reduction of exposure to marketing will be a central part of any successful anti-obesity strategy. PMID- 17341216 TI - Are dietary intakes and eating behaviors related to childhood obesity? A comprehensive review of the evidence. AB - The purpose of this article is to comprehensively review studies that have examined the relation between diet and childhood obesity. The review specifically considers the roles of total energy intake and energy density; dietary composition; individual foods, food groups, and dietary patterns; beverage consumption; and eating behaviors. The paper also discusses methodological considerations and future research directions and concludes by summarizing the evidence presented and highlighting the ethical issues surrounding providing dietary advice. PMID- 17341215 TI - Parental influence on eating behavior: conception to adolescence. AB - The first years of life mark a time of rapid development and dietary change, as children transition from an exclusive milk diet to a modified adult diet. During these early years, children's learning about food and eating plays a central role in shaping subsequent food choices, diet quality, and weight status. Parents play a powerful role in children's eating behavior, providing both genes and environment for children. For example, they influence children's developing preferences and eating behaviors by making some foods available rather than others, and by acting as models of eating behavior. In addition, parents use feeding practices, which have evolved over thousands of years, to promote patterns of food intake necessary for children's growth and health. However in current eating environments, characterized by too much inexpensive palatable, energy dense food, these traditional feeding practices can promote overeating and weight gain. To meet the challenge of promoting healthy weight in children in the current eating environment, parents need guidance regarding alternatives to traditional feeding practices. PMID- 17341218 TI - Actions necessary to prevent childhood obesity: creating the climate for change. AB - Childhood obesity has become a public health epidemic, and currently a battle exists over how to frame and address this problem. This paper explores how public policy approaches can be employed to address obesity. We present the argument that obesity should be viewed as the consequence of a "toxic environment" rather than the result of the population failing to take enough "personal responsibility." In order to make progress in decreasing the prevalence of obesity, we must shift our view of obesity away from the medical model (which focuses on the individual) to a public health model (which focuses on the population). At the same time, we must be sensitive to the problem of weight bias. Potential obstacles to taking a public policy approach are identified, as well as suggestions on how to overcome them. PMID- 17341217 TI - What does the epidemic of childhood obesity mean for children with special health care needs? AB - Bringing the 12.8% of children with special healthcare needs into the national response to the childhood obesity epidemic will require new information, a view of health promotion beyond that which occurs within healthcare systems, and services and supports in addition to the multi-sectoral strategies presently designed for children overall. These efforts are necessary to protect the health of the nation's 9.4 million children with special health care needs now and long term. PMID- 17341219 TI - Application of law to the childhood obesity epidemic. AB - Childhood obesity is in important respects a result of legal policies that influence both dietary intake and physical activity. The law must shift focus away from individual risk factors alone and seek instead to promote situational and environmental influences that create an atmosphere conducive to health. To attain this goal, advocates should embrace a population-wide model of public health, and policymakers must critically examine the fashionable rhetoric of consumer choice. PMID- 17341220 TI - Addressing the epidemic of childhood obesity through school-based interventions: what has been done and where do we go from here? AB - Schools are ideal settings for implementing multi-component programs to prevent and control childhood obesity. Thoughtful improvements to proven strategies, coupled with careful evaluation, can contribute to accumulation of evidence needed to design and implement the next generation of optimal interventions. PMID- 17341221 TI - Community interventions: a brief overview and their application to the obesity epidemic. AB - Community-based interventions built on theory and informed by community members produce potent, sustainable change. This intervention model mobilizes inherent community assets and pinpoints specific needs. Advancing community-based research to address obesity will require training of future leaders in this methodology, funding to conduct rigorous trials, and scientific acceptance of this model. PMID- 17341222 TI - Local venues for change: legal strategies for healthy environments. AB - Mounting evidence documents the extraordinary toll on human health resulting from the consumption of unhealthy food products and physical inactivity. In response to America's growing obesity problem, local policymakers have been looking for legal strategies that can be adopted in their communities to encourage healthful behaviors. In order to provide practical tools to policymakers, this article examines four possible venues for local policy change to improve the health of a community: (1) the school environment (2) the built environment (3) community facilities and (4) the point of sale environment. Finally, the article examines the use of taxes or fees as a means of paying for nutrition policy work as well as potentially reducing the consumption of unhealthy products. This article illustrates that local laws and policies can be a valuable tool in changing a community's environment in order to improve nutritional options and increase opportunities for physical activity. PMID- 17341223 TI - Trends in childhood obesity research: a brief analysis of NIH-supported efforts. AB - Childhood obesity is an increasing health threat. The National Institutes of Health (NIH) is the primary funding agency for research into the causes, mechanisms, consequences, and prevention and treatment of childhood obesity. Using the NIH Strategic Plan for Obesity Research as the framework, this article summarizes the research that has been funded in the past five years as well as new research areas with great potential. PMID- 17341224 TI - Reframing the obesity debate: McDonald's role may surprise you. PMID- 17341225 TI - The politics of palliative care and the ethical boundaries of medicine: Gonzales v. Oregon as a cautionary tale. AB - The U.S. Supreme Court's 6-decision in Gonzales v. Oregon is the latest defeat for the Bush administration in its sustained attack on Oregon's physician assisted suicide law. Both the majority opinion and the major dissent in Oregon provide an opportunity to assess the dangers inherent in allowing a political agenda that emphasizes the sanctity of life and minimizes professional ethical obligations to overshadow quality patient care at the end of life. PMID- 17341226 TI - What is wrong with "ethics for sale"? An analysis of the many issues that complicate the debate about conflicts of interests in bioethics. AB - This article addresses all of the issues involved in the debate about whether or not bioethicists should be paid by private biomedical companies to perform consultations. These issues include the following: differentiation of this role from bioethicists' other roles, an analysis of to whom bioethicists owe a duty, consideration of what bioethicists are "selling," whether bioethicists should be allowed to get paid, when payment becomes problematic, and whether consulting fee arrangements should be regulated. The author often compares bioethicists' relationship to the companies to bioethicists' other relationships, as well as to professional relationships in other fields, such as law and accounting. PMID- 17341227 TI - The best interests standard for incompetent or incapacitated persons of all ages. AB - When making decisions for adults who lack decision-making capacity and have no discernable preferences, widespread support exists for using the Best Interests Standard. This policy appeals to adults and is compatible with many important recommendations for persons facing end-of-life choices. Common objections to the policy are discussed as well as different meanings of this Standard identified, such as using it to express goals or ideals and to make practical decisions incorporating what reasonable persons would want. For reasons of consistency, fairness, and compassion, this standard should be used for all incapacitated persons. PMID- 17341228 TI - The empirical slippery slope from voluntary to non-voluntary euthanasia. AB - This article examines the evidence for the empirical argument that there is a slippery slope between the legalization of voluntary and non-voluntary euthanasia. The main source of evidence in relation to this argument comes from the Netherlands. The argument is only effective against legalization if it is legalization which causes the slippery slope. Moreover, it is only effective if it is used comparatively-to show that the slope is more slippery in jurisdictions which have legalized voluntary euthanasia than it is in jurisdictions which have not done so. Both of these elements are examined comparatively. PMID- 17341229 TI - Concierge medicine: legal and ethical issues. PMID- 17341231 TI - California limits egg donor compensation in privately-funded research. PMID- 17341232 TI - The 21st-century American Geriatrics Society: destinations and highways to get there. PMID- 17341233 TI - Risk factors associated with the occurrence of fractures in U.S. nursing homes: resident and facility characteristics and prescription medications. AB - OBJECTIVES: To determine whether resident and facility characteristics and prescription medications influence the occurrence of fractures in nursing homes (NHs). DESIGN: Panel study with 1-year follow-up. SETTING: A nationally representative sample of NHs from the Medical Expenditure Panel Survey (MEPS). PARTICIPANTS: Residents aged 65 and older who were in sample NHs on January 1, 1996. MEASUREMENTS: Health status measures were collected from facility records and abstracted using a computer-assisted personal interview instrument. Fracture and drug data were updated every 4 months to provide a full year of information. Drug data were obtained from monthly medication administration records. The occurrences of fractures were obtained from medical records. Administered medications were classified using the Department of Veterans Affairs medication classification system. Facility characteristics were based on MEPS survey data collected from NH sources. RESULTS: In 1996, 6% of residents in a NH at the beginning of the year experienced a fracture during their NH stay(s). Resident risk factors included aged 85 and older, admitted from the community, exhibited agitated behaviors, and used both wheelchair and cane or walker. Use of anticonvulsants, antidepressants, opioid analgesics, iron supplements, bisphosphonates, thiazides, and laxatives were associated with fractures. A high certified nurse aide ratio was negatively associated with fractures. CONCLUSION: The findings indicate that fractures are associated with resident and facility characteristics and prescribing practices. It reaffirms the importance of medication review with special attention on opioid analgesics, antidepressants, and anticonvulsants to reduce the risk of fractures. PMID- 17341234 TI - Consequences of an intervention to reduce restrictive side rail use in nursing homes. AB - OBJECTIVES: To examine the effect of an advanced practice nurse (APN) intervention on restrictive side rail usage in four nursing homes and with a sample of 251 residents. A secondary question explored the association between restrictive side rail reduction and bed-related falls. DESIGN: Pre- and posttest design. SETTING: Four urban nursing homes. PARTICIPANTS: All nursing home residents present in the nursing home at three time points (n=710, 719, and 707) and a subset of residents (n=251) with restrictive side rail use at baseline. INTERVENTION: APN consultation with individual residents and facility-wide education and consultation. MEASUREMENTS: Direct observation of side rail status, resident and nurse interview for functional status, mobility, cognition, behavioral symptoms, medical record review for demographics and treatment information, and incident reports for fall data. RESULTS: At the institutional level, one of the four nursing homes significantly reduced restrictive side rail use (P=.01). At the individual participant level, 51.4% (n=130) reduced restrictive side rail use. For the group that reduced restrictive side rails, there was a significantly (P<.001) reduced fall rate (-0.053; 95% confidence interval (CI)=-0.083 to -0.024), whereas the group that continued restrictive side rail did not demonstrate a significantly (P=.17) reduced fall rate (-0.013; 95% CI=-0.056-0.030). CONCLUSION: An APN consultation model can safely reduce side rail use. Restrictive side rail reduction does not lead to an increase in bed-related falls. Although side rails serve many purposes, routine use of these devices to restrict voluntary movement and prevent falls is not supported. PMID- 17341235 TI - Implementation and evaluation of a nursing home fall management program. AB - OBJECTIVES: To evaluate the feasibility and effectiveness of a falls management program (FMP) for nursing homes (NHs). DESIGN: A quality improvement project with data collection throughout FMP implementation. SETTING: NHs in Georgia owned and operated by a single nonprofit organization. PARTICIPANTS: All residents of participating NHs. INTERVENTION: A convenience sample of 19 NHs implemented the FMP. The FMP is a multifaceted quality improvement and culture change intervention. Key components included organizational leadership buy-in and support, a designated facility-based falls coordinator and interdisciplinary team, intensive education and training, and ongoing consultation and oversight by advanced practice nurses with expertise in falls management. MEASUREMENTS: Process-of-care documentation using a detailed 24-item audit tool and fall and physical restraint use rates derived from quality improvement software currently used in all Georgia NHs (MyInnerView). RESULTS: Care process documentation related to the assessment and management of fall risk improved significantly during implementation of the FMP. Restraint use decreased substantially during the project period, from 7.9% to 4.4% in the intervention NHs (a relative reduction of 44%), and decreased in the nonintervention NHs from 7.0% to 4.9% (a relative reduction of 30%). Fall rates remained stable in the intervention NHs (17.3 falls/100 residents per month at start and 16.4 falls/100 residents per month at end), whereas fall rates increased 26% in the NHs not implementing the FMP (from 15.0 falls/100 residents/per month to 18.9 falls/100 residents per month). CONCLUSION: Implementation was associated with significantly improved care process documentation and a stable fall rate during a period of substantial reduction in the use of physical restraints. In contrast, fall rates increased in NHs owned by the same organization that did not implement the FMP. The FMP may be a helpful tool for NHs to manage fall risk while attempting to reduce physical restraint use in response to the Centers for Medicare and Medicaid Services quality initiatives. PMID- 17341236 TI - Can hip protector use in the nursing home be predicted? AB - OBJECTIVES: To identify resident- and caregiver-related factors that influence hip protector (HP) usage. DESIGN: Prospective observational cohort study over 6 weeks. SETTING: A 409-bed nursing home located in New York City. PARTICIPANTS: Fifty-two residents and 60 certified nursing assistants (CNAs). INTERVENTION: Free HPs were provided to residents enrolled in the study. MEASUREMENTS: HP adherence (number of hours HPs were worn/shift); HP users (subjects who used HPs for more than 1 hour during any 8-hour shift as recorded by CNAs in week 6 or who used HPs at checks performed by research staff in week 6 and intended future use); CNAs' scores on a questionnaire quantifying osteoporosis knowledge, opinions on HPs, job satisfaction, and health locus of control. RESULTS: Sixty eight percent of residents were HP users. Factors independently associated with this outcome included male sex, age, Parkinson's disease, family involvement, impaired cognition, dependent ambulation, and CNAs' sense that chance affects health outcomes. In multivariate models, anxiety, resistive behaviors, ambulation, and fall history in residents and CNAs' perceptions of HPs and their sense of how chance or other staff determine health outcomes predicted HP adherence. CONCLUSION: Resident-related factors and CNAs' sense of external controls predicted HP users and HP adherence. CNAs' understanding of osteoporosis and HP affected only HP adherence. Most resident-related factors were not remediable but might help to target likely HP users. To improve HP adherence, educational programs should be designed to improve CNAs' understanding of osteoporosis and HP. Larger studies are needed to confirm these findings. PMID- 17341237 TI - Binocular visual-field loss increases the risk of future falls in older white women. AB - OBJECTIVES: To examine the relationship between binocular visual field loss and the risk of incident frequent falls in older white women. DESIGN: A multicenter, prospective cohort study. SETTING: Four clinic centers within the United States in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania. PARTICIPANTS: Four thousand seventy-one community-dwelling white women aged 70 and older participating in the Study of Osteoporotic Fractures. MEASUREMENTS: Primary outcome was incident frequent falls, defined as two or more falls within 1 year. Primary risk factors were binocular visual field loss, distance visual acuity in the better eye, and contrast sensitivity at low spatial frequency in the better eye. RESULTS: Of 4,071 women, 409 (10%) had severe binocular visual field loss at the eye examination, and 643 (16%) experienced frequent falls within 1 year after their eye examination. Severe binocular visual field loss was significantly associated with frequent falls when adjusting for age, study site, and cognitive function (odds ratio=1.50, 95% confidence interval=1.11-2.02). The data showed a trend for increasing odds of two or more falls with greater binocular visual field loss (P<.001). In older white women with severe binocular visual field loss, 33.3% of frequent falls were attributable to visual field loss. CONCLUSION: Women with binocular visual field loss are at greater risk of future frequent falls. Screening for binocular visual field loss may identify individuals at high risk of falling. PMID- 17341238 TI - Bouncing back: patterns and predictors of complicated transitions 30 days after hospitalization for acute ischemic stroke. AB - OBJECTIVES: To identify predictors of complicated transitions within 30 days after discharge from hospitalization for acute stroke. DESIGN: Retrospective analysis of administrative data. SETTING: Four hundred twenty-two hospitals in the southern and eastern United States. PARTICIPANTS: Thirty-nine thousand three hundred eighty-four Medicare beneficiaries aged 65 and older discharged after acute ischemic stroke from 1998 to 2000. MEASUREMENTS: Complicated transition, defined as movement from less- to more-intensive care setting after hospital discharge, with hospital being most intensive and home without home health care being least intensive. RESULTS: Twenty percent of patients experienced at least one complicated transition; 16% of those experienced more than one complicated transition. After adjustment using logistic regression, factors predicting any complicated transition included older age, African-American race, Medicaid enrollment, prior hospitalization, gastrostomy tube, chronic disease, length of stay, and discharge site. Patients with multiple complicated transitions were more likely to be African American (odds ratio (OR)=1.38, 95% confidence interval (CI)=1.13-1.68), be male (OR=1.21, 95% CI=1.04-1.40), have a prior diagnosis of fluid and electrolyte disorder (e.g., dehydration) (OR=1.23, 95% CI=1.07-1.43), have a prior hospitalization (OR=1.18, 95% CI=1.01-1.36), and be initially discharged to a skilled-nursing facility or long-term care (OR=1.22, 95% CI=1.04 1.44) than patients with only one complicated transition. They were less likely to be initially discharged to a rehabilitation center (OR=0.71, 95% CI=0.57 0.89). CONCLUSION: Significant numbers of stroke patients experience complicated transitions soon after hospital discharge. Sociodemographic factors and initial discharge site distinguish patients with multiple complicated transitions. These factors may enable prospective identification and targeting of stroke patients at risk for "bouncing back." PMID- 17341239 TI - Stroke-independent association between metabolic syndrome and functional dependence, depression, and low quality of life in elderly community-dwelling Brazilian people. AB - OBJECTIVES: Metabolic syndrome (Met.S) is a risk factor for stroke, dementia, and ischemic heart disease (IHD). It is unclear whether Met.S is an independent risk factor for functional dependence, depression, cognitive impairment, and low health-related quality of life (HRQoL) in a population free of clinical stroke. DESIGN: Cross-sectional. SETTING: Two communities in southern Brazil. PARTICIPANTS: Four hundred twenty people aged 60 and older. MEASUREMENTS: An adapted (body mass index > or =30 kg/m(2) and blood pressure > or =140/90) Adult Treatment Panel III definition was used in diagnosing Met.S. Depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Revised) and Mini-Mental State Examination were evaluated along with activities of daily living (ADLs) and instrumental activities of daily living (IADLs). HRQoL was measured using a visual analogue scale (0-10). All values were adjusted for age, sex, and presence of IHD. RESULTS: Forty (9.5%) subjects had a stroke and were excluded from the final analysis. Met.S was present in 37.4% of the stroke-free population. Met.S was significantly and independently associated with 2.24 times as much ADL dependence, 2.39 times as much IADL dependence, a 2.12 times higher risk of depression, a 2.27 times higher likelihood of cognitive impairment, and a 1.62 times higher chance of low self-perceived HRQoL (all P<0.05). Adjustment for its own components reduced the strength of the above associations but did not eliminate their statistical significance. If Met.S were removed from this population, dependence, depression, cognitive impairment, and low QoL would be reduced 15.0% to 21.4%. CONCLUSION: Met.S was significantly associated with functional dependence, depression, cognitive impairment, and low HRQoL, and its effects were independent of clinical stroke, IHD, and its own individual components. PMID- 17341240 TI - Blood pressure and survival in the oldest old. AB - OBJECTIVES: To determine the relationship between blood pressure (BP) and all cause mortality in subjects aged 80 and older with hypertension. DESIGN: Retrospective cohort study with 5 years of follow-up. SETTING: Ten Veterans AFFAIRS (VA) sites. PARTICIPANTS: Four thousand seventy-one ambulatory patients aged 80 and older with hypertension. MEASUREMENTS: The outcome measure was likelihood of survival during the follow-up period. Vital status was obtained from VA and Social Security files. Variables collected for adjustment in Cox regression models were baseline BP, medications, demographics, diagnoses, and health-related quality of life (HRQoL); HRQoL information was available on 1,289 subjects based on Veterans Health Study Short From-36 (SF-36) questionnaire scores. RESULTS: Subjects with higher BP (up to a systolic BP (SBP) of 139 mmHg and a diastolic BP (DBP) of 89 mmHg) were less likely to die during follow-up than subjects with lower BP. After baseline adjustments, the hazard ratio for a 10-point increase in SBP was 0.82 (95% confidence interval (CI)=0.74-0.91), up to a SBP of 139 mmHg, and for DBP was 0.85 (95% CI=0.78-0.92), up to a DBP of 89 mmHg. There was no significant association between survival and BP levels in subjects with uncontrolled hypertension. CONCLUSION: In a cohort of very old, hypertensive veterans, in subjects with controlled BPs, subjects with lower BP levels had a lower 5-year survival than those with higher BPs. This suggests that clinicians should use caution in their approach to BP lowering in this age group. PMID- 17341241 TI - Is age associated with the number or types of medications prescribed to renal transplant recipients? AB - OBJECTIVES: To determine whether age influences the number or types of medications prescribed to younger (aged 18-64) and elderly (aged > or =65) renal transplant recipients 3 years posttransplant. DESIGN: A cross-sectional study involving renal transplant recipients. SETTING: Medical College of Georgia. PARTICIPANTS: A random sample of 100 elderly and 100 younger renal transplant recipients who received posttransplant care at the Medical College of Georgia, were on stable immunosuppressant therapy regimens, and were at least 3 years posttransplant. MEASUREMENTS: Medical and pharmacy data of recipients were evaluated for demographics; presence of a lipid-lowering agent; number of antihypertensives, immunosuppressants, antidiabetic agents, and total medications; number of rejections; dose per kilogram of immunosuppressant(s); infection-related hospitalizations; and measures of blood pressure, blood glucose, serum creatinine, serum tacrolimus/cyclosporine concentrations, total cholesterol, and triglycerides. RESULTS: Elderly recipients were more likely to have diabetes mellitus before the transplant and to develop diabetes mellitus afterwards (P=.04) and were prescribed more total medications (12.40+/-3.72 vs 10.25+/-4.07, P<.001) and antidiabetic agents (0.89+/-0.93 vs 0.42+/-0.77, P<.001) 3 years posttransplant than younger recipients. Elderly recipients also had fewer chronic rejections, more infection-related hospitalizations, lower diastolic blood pressure, and greater fasting blood glucose levels 3 years posttransplant (P<.05) than younger recipients. CONCLUSION: Future investigation should focus on deciphering the implications of the greater numbers of medications prescribed to elderly renal transplant recipients in terms of maximizing desired health outcomes (e.g., graft survival) and minimizing adverse drug-related experiences (e.g., infection). PMID- 17341242 TI - Vasodilators and nootropics as predictors of dementia and mortality in the PAQUID cohort. AB - OBJECTIVES: To assess the effects of treatment for memory impairment and the Ginkgo biloba extract (EGb 761) on dementia, mortality, and survival without dementia. DESIGN: Prospective community-based cohort study. SETTING: France. PARTICIPANTS: Three thousand five hundred thirty-four subjects aged 65 and older. MEASUREMENTS: Information on drug consumption was obtained by interview and visual assessment of patients' medicine chests. Active screening of dementia was performed every 2 years over a 13-year period. The independent effects of treatment for memory impairment and the Ginkgo biloba extract on the risks of dementia and death were estimated using Cox proportional hazards models, adjusted for potentially confounding factors (including comorbidities). RESULTS: The initial consumption of Ginkgo biloba did not modify the risk of dementia (relative risk (RR)=1.16, 95% confidence interval (CI)=0.84-1.60), whereas the consumption of other treatments for memory impairment was associated with a higher risk of dementia (RR=1.35, 95% CI=1.11-1.63). Subjects who took Ginkgo biloba had a significantly lower risk of mortality in the long term (RR=0.76, 95% CI=0.62-0.93), even after adjustment for potentially confounding factors. The initial consumption of treatment for memory impairment other than Ginkgo biloba did not modify the risk of mortality. CONCLUSION: These results suggest that treatment with EGb 761 may increase the probability of survival in the elderly population. These findings need to be corroborated and further assessed using randomized, controlled trials. PMID- 17341243 TI - Lower extremity ischemia, calf skeletal muscle characteristics, and functional impairment in peripheral arterial disease. AB - OBJECTIVES: To determine whether lower ankle brachial index (ABI) levels are associated with lower calf skeletal muscle area and higher calf muscle percentage fat in persons with and without lower extremity peripheral arterial disease (PAD). DESIGN: Cross-sectional. SETTING: Three Chicago-area medical centers. PARTICIPANTS: Four hundred thirty-nine persons with PAD (ABI<0.90) and 265 without PAD (ABI 0.90-1.30). MEASUREMENTS: Calf muscle cross-sectional area and the percentage of fat in calf muscle were measured using computed tomography at 66.7% of the distance between the distal and proximal tibia. Physical activity was measured using an accelerometer. Functional measures included the 6-minute walk, 4-meter walking speed, and the Short Physical Performance Battery (SPPB). RESULTS: Adjusting for age, sex, race, comorbidities, and other potential confounders, lower ABI values were associated with lower calf muscle area (ABI<0.50, 5,193 mm(2); ABI 0.50-0.90, 5,536 mm(2); ABI 0.91-1.30, 5,941 mm(2); P for trend<.001). These significant associations remained after additional adjustment for physical activity. In participants with PAD, lower calf muscle area in the leg with higher ABI was associated with significantly poorer performance in usual- and fast-paced 4-meter walking speed and on the SPPB, adjusting for ABI, physical activity, percentage fat in calf muscle, muscle area in the leg with lower ABI, and other confounders (P<.05 for all comparisons). CONCLUSION: These data support the hypothesis that lower extremity ischemia has a direct adverse effect on calf skeletal muscle area. This association may mediate previously established relationships between PAD and functional impairment. PMID- 17341244 TI - Heterogeneity in hip fracture patients: age, functional status, and comorbidity. AB - OBJECTIVES: To examine unidentified heterogeneity in hip fracture patients that may predict variation in functional outcomes. DESIGN: Observational, longitudinal, multisite cohort study. SETTING: Three separate cohorts from five hospitals in the metropolitan New York area and eight hospitals in Baltimore. PARTICIPANTS: Two thousand six hundred ninety-two hip fracture patients treated at one of 13 hospitals and followed for 6 months postfracture. MEASUREMENTS: A mobility measure with three categories (independent (walks independently or with a device), limited independence (needs human assistance or supervision to walk 150 feet or one block or able only to walk indoors), and unable to walk) was developed for use with all three cohorts. A similar measure was developed for the other activities of daily living (ADLs): bathing, dressing, feeding, and using the toilet. Cluster analysis was used to form homogenous groups of patients based on baseline demographic characteristics, comorbid conditions, and baseline mobility and ADL independence. RESULTS: Seven homogeneous subgroups were identified based on prefracture age, health, and functional status, with measurably different 6-month functional outcomes. At least 90% of patients could be correctly classified into the seven groups using simple decision rules about age, ADLs, and dementia status at baseline. Dementia was the only comorbid condition that segmented the groups. CONCLUSION: The heterogeneous hip fracture population can be grouped into homogenous patient clusters based on prefracture characteristics. Differentially targeting services and interventions to these subgroups may improve functional status outcomes. PMID- 17341245 TI - Pneumonia and lower respiratory infections in nursing home residents: predictors of hospitalization and mortality. AB - OBJECTIVES: To compare predictors of hospitalization and death in nursing home residents with pneumonia and other lower respiratory infections (LRIs). DESIGN: A nested cohort study. SETTING: Nine nursing homes in southern Ontario. PARTICIPANTS: Three hundred fifty-three nursing home residents with LRIs (enrolled in the control arm of a clinical trial). MEASUREMENTS: Comorbidities, vaccination status, age, health-related quality of life, functional status, and vital statistics were evaluated as potential predictors of hospitalization and mortality at 30 days. RESULTS: Moderate to high disease severity score on a practical severity scale was a strong independent predictor of hospitalization (odds ratio (OR)=7.12, P<.001) and mortality (OR=5.04, P=.003). Diagnosis of pneumonia, established using chest radiograph, was also associated with hospitalization (OR=2.43, P=.008) and mortality (OR=2.35, P=.02). Oxygen saturation (<90%) was a strong independent predictor of hospitalization (OR=3.02, P=.004) but was not a significant predictor of mortality in multivariable analyses. Diagnosis of congestive heart failure (OR=2.26, P=.02) was an independent predictor of hospitalization, whereas receipt of pneumococcal vaccine (OR=0.36, P=.01) and greater functional independence (OR=0.92, P=.02) were negatively associated with hospitalization. CONCLUSION: In nursing home residents with LRI, severity of illness and radiographically confirmed pneumonia are predictive of death and hospitalization. PMID- 17341246 TI - Effects of statin use on muscle strength, cognition, and depressive symptoms in older adults. AB - OBJECTIVES: To determine the relationship between hydroxymethyl glutaryl coenzyme A reductase inhibitor (statin) use and proximal muscle strength, cognition, and depression in older adults. DESIGN: Observational cohort study. SETTING: Outpatient primary care clinics. PARTICIPANTS: Seven hundred fifty-six community dwelling veterans aged 65 and older. MEASUREMENTS: Timed chair stands (a measure of proximal muscle strength), Trail Making Test Part B (a measure of cognition), and the Center for Epidemiologic Studies Depression Scale score were measured at baseline and 1-year follow-up. Participants were assessed for statin prescriptions (and indications for or contraindications to their use), concomitant medication use, comorbidities, and other potential confounders. RESULTS: Statin users (n=315) took a mean 6.6 medications, versus 4.6 for nonusers (n=441), and had a median duration of statin use of 727 days. Statin users were more likely to be white and had (as expected) more cardiac, cerebrovascular, and peripheral vascular disease. Based on multivariable models adjusting for pertinent covariates, statin users performed modestly better than nonusers for timed chair stands (-0.5 seconds; P=.04), Trail Making Test Part B ( 7.7 seconds; P=.08), and depression scores (-0.2 points; P=.49) at follow-up. Of potentially high-risk participants (based on age, comorbidity, and number of medications), statin users also showed similar 1-year changes as nonusers, although worsened depression scores were found in those with greater comorbidity (+0.88 points; P=.10). CONCLUSION: Older, community-dwelling male participants taking maintenance statin therapy had similar outcomes to those of nonusers in tests of muscle strength, cognition, and depression, but further examination of benefits and harms in different subgroups is warranted. PMID- 17341247 TI - The effect of 3-year treatment with 0.25 mg/day of micronized 17beta-estradiol on cognitive function in older postmenopausal women. AB - OBJECTIVES: To evaluate the effect of ultra-low-dose (0.25 mg/d) micronized 17beta-estradiol on cognitive function in older postmenopausal women. DESIGN: Randomized, placebo-controlled trial conducted for 3 years. SETTING: Academic health center in greater Hartford, Connecticut. PARTICIPANTS: Fifty-seven healthy, community-dwelling, older postmenopausal women. INTERVENTION: Women received 0.25 mg/d of micronized 17beta-estradiol (estrogen therapy (ET), n=32) or placebo (n=25); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MEASUREMENTS: Neuropsychological measures of memory, language, mood, and executive function were collected at baseline, 3 months, and 36 months. Measures of executive function included the Controlled Oral Word Association Test, the Trail Making Test, and the Wisconsin Card Sorting Test. The Boston Naming Test was used to measure language skills. The Symbol Digit Modalities Test was used as a measure of sustained attention. Measures of memory included the Complex Figure Test, Fuld Object Memory Test, and a selected subtest from the Wechsler Memory Scale. Scores from the Geriatric Depression Scale and the Beck Anxiety Inventory were used to assess symptoms of depression. RESULTS: No differences were found between ET and placebo on any of the neurocognitive measures or depression instruments, nor were there any differences when the groups were stratified according to age. CONCLUSION: This small study, which had adequate power to detect change in some but not all domains of cognition tested, revealed that low-dose estrogen neither benefits nor harms cognitive function in older women after 3 years of treatment, but confirmation is needed from larger trials. PMID- 17341248 TI - Decisions to forgo hospitalization in advanced dementia: a nationwide study. AB - OBJECTIVES: To examine the prevalence and factors associated with decisions to forgo hospitalization in nursing home (NH) residents with advanced dementia. DESIGN: Cross-sectional study. SETTING: All Medicare- and Medicaid-certified NHs within the 48 contiguous U.S. states. PARTICIPANTS: NH residents with advanced dementia were identified using Minimum Data Set (MDS) assessments completed close to April 1, 2000 (N=91,521). MEASUREMENTS: Multilevel, multivariate logistic regression identified factors independently associated with having a do-not hospitalize (DNH) directive. Independent variables included subject characteristics (MDS), facility factors (On-line Survey of Certification of Automated Records), and hospital referral region (HRR) features (Dartmouth Atlas). RESULTS: Nationwide, 7.1% (n=6,518) residents with advanced dementia had DNH orders (range 0.7% in Oklahoma to 25.9% in Rhode Island). Resident characteristics associated with having a DNH order were older age, white, living will, durable power of attorney for health care, and total functional dependence. Controlling for these factors, DNH orders were more likely in residents of facilities with the following features: not part of a chain, urban location, special care dementia unit, fewer black residents, nurse practitioner or physician assistant on staff, higher staffing ratios, and location in HRRs with fewer intensive care unit admissions during terminal hospitalizations. CONCLUSION: Directives to forgo hospitalization for U.S. NH residents with advanced dementia are uncommon and are associated with the organizational features of the facilities caring for them and the intensity of end-of-life care practiced in the region, as well as individual resident characteristics. PMID- 17341249 TI - Case management and risk of nursing home admission for older adults in home care: results of the AgeD in HOme Care Study. AB - OBJECTIVES: To explore the relationship between a case management approach and the risk of institutionalization in a large European population of frail, old people in home care. DESIGN: Retrospective cohort study. SETTING: Eleven European countries. PARTICIPANTS: Three thousand two hundred ninety-two older adults receiving home care (mean age 82.3+/-7.3). MEASUREMENTS: Data on nursing home admission were collected every 6 months for 1 year. RESULTS: One thousand one hundred eighty-four (36%) persons received a home care program based on case management, and 2,108 (64%) received a traditional care approach (no case manager). During the 1-year follow-up, 81 of 1,184 clients (6.8%) in the case management group and 274 of 2,108 (13%) in the traditional care group were admitted to a nursing home (P<.001). After adjusting for potential confounders, the risk of nursing home admission was significantly lower for participants in the case management group than for those in a traditional care model (adjusted odds ratio=0.56, 95% confidence interval=0.43-0.63). CONCLUSION: Home care services based on a case management approach reduce risk of institutionalization and likely lower costs. PMID- 17341250 TI - Adding an alcohol-related risk score to an existing categorical risk classification for older adults: sensitivity to group differences. AB - OBJECTIVES: To evaluate a new alcohol-related risk score for research use. DESIGN: Using data from a previously reported trial of a screening and education system for older adults (Computerized Alcohol-Related Problems Survey), secondary analyses were conducted comparing the ability of two different measures of risk to detect post-intervention group differences: the original categorical outcome measure and a new, finely grained quantitative risk score based on the same research-based risk factors. SETTING: Three primary care group practices in southern California. PARTICIPANTS: Six hundred sixty-five patients aged 65 and older. MEASUREMENTS: A previously calculated, three-level categorical classification of alcohol-related risk and a newly developed quantitative risk score. RESULTS: Mean post-intervention risk scores differed between the three experimental conditions: usual care, patient report, and combined report (P<.001). The difference between the combined report and usual care was significant (P<.001) and directly proportional to baseline risk. The three-level risk classification did not reveal approximately 57.3% of the intervention effect detected by the risk score. The risk score also was sufficiently sensitive to detect the intervention effect within the subset of hypertensive patients (n=112; P=.001). CONCLUSION: As an outcome measure in intervention trials, the finely grained risk score is more sensitive than the trinary risk classification. The additional clinical value of the risk score relative to the categorical measure needs to be determined. PMID- 17341251 TI - Knee extension strength cutpoints for maintaining mobility. AB - OBJECTIVES: To identify levels of knee extensor strength that are associated with high and low risk of incident severe mobility limitation (SML) in initially well functioning older adults. DESIGN: Prospective cohort study. SETTING: University clinic center. PARTICIPANTS: One thousand three hundred fifty-five men and 1,429 women (aged 73.6+/-2.85) who reported no mobility limitation. MEASUREMENTS: Unilateral knee extensor isokinetic strength of participants was obtained. Participants were followed over a median of 5.90 years for the onset of SML, defined as two consecutive reports of a lot of difficulty or inability to walk one-quarter of a mile or climb 10 steps. Deciles of knee extension strength relative to body weight were evaluated to identify cutpoints most predictive of incident SML. Cutpoints were then compared with prevalence of having slow gait speed (<1.22 m/s) and mortality. RESULTS: Two sex-specific knee extension strength cutpoints were found. High and low risk of SML corresponded to less than 1.13 newton-meters (Nm)/kg (1st decile) and more than 1.71 Nm/kg (6th decile) in men and less than 1.01 Nm/kg (3rd decile) and more than 1.34 Nm/kg (7th decile) in women, respectively. Moderate risk was defined as being between the low- and high-risk cutpoints. Individuals with knee extension strength in the high- and moderate-risk categories were more likely to have a gait speed less than 1.22 m/s (hazard ratio (HR)=7.00, 95% confidence interval (CI)=5.47-8.96 and HR=2.14 7.00, 95% CI=1.73-2.64, respectively) and had a higher risk of death (HR=1.77, 95% CI=1.41-2.23 and HR=1.51, 95% CI=1.24-1.84, respectively) than individuals in the low-risk category. Adjustment for demographic factors, health behaviors, and medical conditions did not alter these associations. CONCLUSION: Knee extensor strength cutpoints provide objective markers to identify initially well functioning older adults at high and low risk of future mobility limitation. PMID- 17341252 TI - The Consortium of E-Learning in Geriatrics Instruction. AB - This paper describes the activities of the Consortium of E-Learning in Geriatrics Instruction (CELGI), a group dedicated to creating, using, and evaluating e learning to enhance geriatrics education. E-learning provides a relatively new approach to addressing geriatrics educators' concerns, such as the shortage of professionals trained to care for older people, overcrowded medical curricula, the move to transfer teaching venues to community settings, and the switch to competency-based education models. However, this innovative education technology is facing a number of challenges as its use and influence grow, including proof of effectiveness and efficiency. CELGI was created in response to these challenges, with the goal of facilitating the development and portability of e learning materials for geriatrics educators. Members represent medical and nursing schools, the Department of Veterans Affairs healthcare system, long-term care facilities, and other institutions that rely on continuing streams of quality health education. CELGI concentrates on providing a coordinated approach to formulating and adapting specifications, standards, and guidelines; developing education and training in e-learning competencies; developing e-learning products; evaluating the effect of e-learning materials; and disseminating these materials. The vision of consortium members is that e-learning for geriatric education will become the benchmark for valid and successful e-learning throughout medical education. PMID- 17341253 TI - Intervening to prevent falls and fractures in nursing homes: are we putting the cart before the horse? PMID- 17341254 TI - How can we ground the "frequent fliers"? PMID- 17341255 TI - Dietary polyunsaturated fatty acid supplementation, pre-dementia syndromes, and Alzheimer's disease. PMID- 17341256 TI - Unawareness of memory deficits depending on cerebral perfusion pattern in mild cognitive impairment. PMID- 17341257 TI - What is the true association between nursing home location and hospitalization of its residents? PMID- 17341260 TI - When eye signs can be misleading. PMID- 17341259 TI - Healthcare professional surveys: judicious antibiotic use in Minnesota long-term care facilities. PMID- 17341261 TI - Diabetic foot infections in older people with end-stage renal disease: primary amputation versus "foot-sparing surgery". PMID- 17341263 TI - Modern management of haemophilic arthropathy. AB - Currently available factor concentrates for treatment of patients with haemophilia are virally inactivated or are made by recombinant technology and their broad use in developed nations has resulted in the dramatic elimination of the treatment-related viral illnesses that decimated the haemophilia community in the late 20th century. The major morbidity experienced by patients with haemophilia today is joint disease, a result of repeated bleeding episodes into joint spaces. Although administration of factor concentrates to prevent bleeding has been demonstrated to prevent haemophilic joint disease when applied assiduously, repeated bleeding episodes induce synovitis that is irreversible and may progress despite subsequent prophylaxis. Surgical and nuclear medicine interventions are available to reduce the pain of haemophilic arthropathy and to reduce further bleeding episodes. Patients with high titre inhibitors are at great risk for the development of joint disease and present the greatest therapeutic challenges when joint surgery is needed. PMID- 17341264 TI - The pathogenesis of transfusion-related acute lung injury (TRALI). AB - In recent years, transfusion-related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, non-cardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patient's co-morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction. PMID- 17341265 TI - Immune anaemias in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab--incidence and predictors. AB - Immune anaemias (IA) [auto-immune haemolytic anaemia (AIHA) and pure red cell aplasia (PRCA)] are complications of chronic lymphocytic leukaemia (CLL). Fludarabine has been associated with AIHA, whereas both rituximab and cyclophosphamide have been used to treat this condition. Combining these agents with fludarabine may reduce the likelihood of AIHA. We report on the incidence, outcome and pretreatment predictors of IA in 300 patients treated with fludarabine, cyclophosphamide and rituximab (FCR). Nineteen patients (6.5%) developed IA [AIHA (5.8%), PRCA (0.7%)] on or after treatment with FCR. Most patients (82.4%) with AIHA had a negative direct antiglobulin test (DAT). Additional markers of haemolysis (indirect hyperbilirubinaemia, reticulocytosis, low haptoglobin and elevated lactate dehydrogenase levels) confirmed the presence of AIHA in these patients. The majority of patients responded to therapies including steroids, ciclosporin, i.v. immunoglobulin, etc. High pretreatment levels of beta-2 microglobulin predicted for development of IA. No haemolytic crisis was observed during FCR therapy in eight patients with AIHA prior to FCR. Thus, the incidence of IA among CLL patients treated with FCR was comparable with historical rates. The diagnosis of AIHA can be considered even if the DAT is negative. Pre-existing AIHA need not preclude front-line FCR therapy. PMID- 17341266 TI - An interphase fluorescence in situ hybridisation assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies. AB - Chromosome rearrangements involving band 3q26.2 are associated with myeloid malignancies, aberrant expression of the human ecotropic virus integration site-1 (EVI1) gene, an unfavourable prognosis and an aggressive clinical course. The 3q26.2 rearrangements are characteristically heterogeneous and typically difficult to detect in poor quality metaphases. To develop a dual-colour fluorescence in situ hybridisation (FISH) assay for the detection of 3q26.2/EVI1 aberrations, a series of 10 BAC clones corresponding to the EVI1 gene region were systematically evaluated and narrowed down to two probe sets; one probe set encompassed the EVI1 gene extending centromeric, while the second probe set covered the EVI1 gene and extends telomeric. Both probe sets were evaluated on 35 patient samples with cytogenetically defined 3q26.2 rearrangements collected at various treatment time points, the inv(3)(q21q26.2) Kasumi-4 cell line, and 10 known negative samples. The two-probe set strategy identified all samples, despite the vast breakpoint heterogeneity observed. In samples from acute myeloid leukaemia and myelodysplastic syndrome cases, the majority of inversion breakpoints were 3' to EVI1 whereas 3q26.2 translocation breakpoints frequently mapped 5' to EVI1. However, two 3q26.2 translocation samples had breakpoints 3' to EVI1. Most inv(3q) chronic myeloid leukaemia samples showed breakpoints within the EVI1 gene. This study demonstrated that, despite the extensive breakpoint heterogeneity observed with 3q26.2 aberrations, this FISH strategy is effective for the detection of 3q26.2 abnormalities in myeloid malignancies. PMID- 17341267 TI - The proteasome inhibitors bortezomib and PR-171 have antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cells. AB - Proteasome inhibitors represent a new class of antineoplastic drugs that are considered in the treatment of haematological malignancies. We compared the effects of the reversible proteasome inhibitor bortezomib (Velcade) and the epoxomicin derivative PR-171, an irreversible inhibitor, on primary human acute myeloid leukaemia (AML) cells. Both drugs inhibited autocrine- and cytokine dependent proliferation of primary AML blasts when tested at nanomolar levels (0.1-100 nmol/l). The antiproliferative effect was independent of basal chymotrypsin-like proteasome activity (showing a 20-fold variation between patients), genetic abnormalities, morphological differentiation and CD34 expression when testing a large group of consecutive patients (n = 54). The effect was retained in cocultures with bone marrow stromal cells. In addition, both drugs enhanced apoptosis. The effect of PR-171 could be detected at lower concentrations than for bortezomib, especially when testing the influence on clonogenic AML cell proliferation. Both drugs had divergent effects on AML cells' constitutive cytokine release. Furthermore, both drugs caused a decrease in proliferation and viability when tested in combination with idarubicin or cytarabine. An antiproliferative effect on primary human acute lymphoblastic leukaemia cells was also detected. We conclude that nanomolar levels of the proteasome inhibitors tested had dose-dependent antiproliferative and proapoptotic effects on primary AML cells in vitro. PMID- 17341268 TI - Frequent epigenetic silencing of protocadherin 10 by methylation in multiple haematologic malignancies. AB - Epigenetic silencing of tumour suppressor genes (TSG) inactivates TSG functions. Previously, we identified PCDH10 as a methylated TSG in carcinomas. Here, we detected its frequent silencing and methylation in lymphoma cell lines including 100% Burkitt, 100% diffuse large B cell, 86% Hodgkin, 100% nasal natural killer/T cell lymphoma and 1/3 of leukaemia cell lines, and in primary tumours but not in normal peripheral blood mononuclear cells or lymph nodes. PCDH10 silencing could be reversed by demethylation with 5-aza-2'-deoxycytidine. Methylation was further detected in 14% of Hodgkin lymphoma sera. Thus, PCDH10 methylation is frequently involved in lymphomagenesis and could serve as a tumour-specific biomarker. PMID- 17341269 TI - Factors for graft-versus-host disease after donor lymphocyte infusions with an escalating dose regimen: lack of association with cell dose. AB - We investigated the risk factors for graft-versus-host disease (GVHD) in 82 patients treated with donor lymphocyte infusions (DLI) using an escalating dose regimen for chronic myeloid leukaemia in relapse following conventional allografting. Two factors emerged as predictors of both acute and chronic GVHD: the infusion of male recipients with lymphocytes from a female donor and the interval between transplant and last DLI, but only the first remained significant at multivariate analysis. Surprisingly, lymphocyte dose did not influence the incidence of GVHD. Our results suggest that DLI can be given in large cell doses without increasing the risk of GVHD. PMID- 17341270 TI - Absence of cytokine modulation following therapeutic infusion of intravenous immunoglobulin or anti-red blood cell antibodies in a mouse model of immune thrombocytopenic purpura. AB - Human intravenous immunoglobulin (IVIg) and anti-D immunoglobulin preparations are used in the treatment of immune thrombocytopenic purpura (ITP). One mechanism proposed to explain their therapeutic effects in ITP patients is the induction of expression of anti-inflammatory cytokines, such as interleukin (IL)-10 or IL-1ra, leading to a reduction of phagocytic activity of the reticuloendothelial system. However, increased expression of pro-inflammatory cytokines was also noted following treatment of ITP patients, raising doubt on the actual contribution of anti-inflammatory cytokines in the therapeutic effects of IVIg and anti-D immunoglobulins. The present study evaluated the in vivo modulation of expression of a large array of inflammatory cytokines using a mouse model of thrombocytopenia. IVIg was not found to modulate cytokine expression although it efficiently prevented thrombocytopenia. In contrast, protective (M1/69) and non protective (TER-119) anti-mouse red blood cell (RBC) antibodies (mimicking anti-D treatment) both increased the expression of CXCL-1 and CXCL-5. Thus, there was no relationship between inflammatory cytokine expression and prevention of thrombocytopenia by IVIg or anti-mouse RBC in the ITP mouse model. These results suggest that the increase in cytokine expression observed in ITP patients following IVIg or anti-D infusion is not required for their therapeutic effects but may rather represent a side-effect of the treatment. PMID- 17341271 TI - The associations between air quality and the number of hospital admissions for acute pain and sickle-cell disease in an urban environment. AB - The clinical severity of sickle-cell disease (SCD) is dependent on genetic and environmental variables. Environmental factors have been poorly studied. We have investigated possible links between air pollution and acute pain in SCD. We retrospectively studied the numbers of daily admissions with acute sickle-cell pain to King's College Hospital, London, in relation to local daily air quality measurements. We analysed 1047 admissions over 1400 d (1st January 1998-31st October 2001). Time series analysis was performed using the cross-correlation function (CCF). CCF showed a significant association between increased numbers of admissions and low levels of nitric oxide (NO), low levels of carbon monoxide (CO) and high levels of ozone (O(3)). There was no association with sulphur dioxide (SO(2)), nitrogen dioxide or PM(10) (dust). The significant results were further examined using quartile analysis. This confirmed that high levels of O(3) and low levels of CO were associated with increased numbers of hospital admissions. Low NO levels were also associated with increased admissions but did not reach statistical significance on quartile analysis. Our study suggests air quality has a significant effect on acute pain in SCD and that patients should be counselled accordingly. The potential beneficial effect of CO and NO is intriguing and requires further investigation. PMID- 17341273 TI - Palifermin and palmar-plantar erythrodysesthesia. PMID- 17341274 TI - Nephrotic syndrome associated with thrombotic microangiopathy following allogeneic stem-cell transplantation for myelodysplastic syndrome. PMID- 17341272 TI - Unexplained anaemia in older persons is characterised by low erythropoietin and low levels of pro-inflammatory markers. AB - Epidemiological studies report that a third of the cases of anaemia in older persons is unexplained. We compared erythropoietin (EPO), inflammatory markers and major comorbidities between older subjects with normal haemoglobin levels and those with different aetiologic forms of anaemia, including unexplained anaemia. Participants were a representative sample of 964 persons aged > or =65 years, with no evidence of bleeding, complete blood tests, and a complete blood count within 6 h of phlebotomy. Anaemia was defined as haemoglobin <130 g/l in men and 120 g/l in women, and classified as a result of chronic kidney disease, iron deficiency, chronic disease and B12/folate deficiency anaemia, or unexplained anaemia based on standard criteria. Of the 124 anaemic participants, 42 (36.8%) had unexplained anaemia. Participants with anaemia of chronic diseases had significantly higher interleukin-6 (IL-6) and C-reactive protein (CRP) levels, while those with unexplained anaemia had significantly lower CRP than non-anaemic controls. Iron deficiency anaemia was characterised by significantly higher EPO levels compared with other types of anaemia and normal haemoglobin, B12 and/or folate deficiency. Unexplained anaemia was characterised by unexpectedly low EPO and low lymphocyte count. Unexplained anaemia is associated with reduced kidney EPO response, low levels of pro-inflammatory markers and low lymphocyte counts. PMID- 17341277 TI - Comparison of nonelective removal of percutaneously versus surgically placed central venous catheters in high-risk neonates. PMID- 17341278 TI - Women and attention deficit disorders: a great burden overlooked. AB - PURPOSE: To describe adult attention-deficit/hyperactivity disorder (ADHD) in relation to gender-based differences in symptom expression with particular emphasis on disparities concerning women, psychiatric comorbidities that affect assessment and detection, and evidenced-based treatment approaches for nurse practitioners (NPs). DATA SOURCES: Health sciences literature was reviewed using the following data-bases: Medline, Cumulative Index to Nursing and Allied Health Literature, PubMed, Proquest, Psych Info, Wiley Interscience, Cambridge Press, Science Direct, and Thomson Gale. CONCLUSIONS: Recognizing adult ADHD may be challenging; however, with increased understanding regarding the subtle variations in symptoms, use of screening instruments, and careful assessment techniques, NPs will be better able to recognize the characteristics of ADHD that are important to early detection, proper diagnosis, and effective treatment. IMPLICATIONS FOR PRACTICE: Additional research and improved clinician education may facilitate early detection and treatment of ADHD among adults of all ages and ethnic/racial backgrounds. PMID- 17341279 TI - Chronic obstructive pulmonary disease: diagnosis and management. AB - PURPOSE: The purpose of this article is to provide a comprehensive review of the current modalities employed in diagnosing and treating chronic obstructive pulmonary disease (COPD). Special emphasis is placed on current guidelines, as defined by the Global Initiative for Chronic Obstructive Lung Disease. DATA SOURCE: A comprehensive literature review for COPD serves as the basis for this article. CONCLUSIONS: According to the National COPD Coalition (2004), there are nearly 24 million Americans who suffer from COPD. The incidence of COPD is rising globally and is associated with increased morbidity and mortality. COPD is characterized by progressive decline in function, resulting in concomitant diseases, which increase healthcare dollar expenditures, thus making COPD a concern for healthcare providers in the United States and abroad. IMPLICATIONS FOR PRACTICE: Once a diagnosis of COPD is made, healthcare providers should explore multiple treatment options in an effort to find the most beneficial regimen. It is only when the treatments are individualized, including physiological therapies and cognitive approaches to lessen risks as well as to reduce exacerbations, that the patient with COPD is able to potentially experience a reasonable quality of life. PMID- 17341280 TI - Does gum chewing help prevent impaired gastric motility in the postoperative period? AB - PURPOSE: To discuss the pathophysiology of postoperative ileus (POI) and the addition of gum chewing to a multimodal treatment plan. DATA SOURCES: Review of current literature of the pathophysiology of POI, multimodal treatment options, and current research on gum chewing and its effects on the prevention of POI. CONCLUSIONS: Studies have documented that gum chewing decreases time to flatus and first defecation after surgery. Studies indicate that gum chewing can decrease the length of hospital stay by 1 day. There were no documented adverse effects of gum chewing. The addition of gum chewing to a multimodal treatment program assists with increasing patient comfort, satisfaction, and decreasing healthcare expenditures. IMPLICATIONS FOR PRACTICE: POI is a common complication of abdominal surgery. Research has indicated that gum chewing has assisted with increasing gastric motility, decreasing lengths of hospital stays, and decreasing healthcare expenditures. Gum chewing is an inexpensive and safe option to add to a multimodal program for the prevention of POI. PMID- 17341282 TI - Embattled and embittered or empowered and evolving: nurse practitioner attitudes toward managed care. AB - PURPOSE: To explore the attitudes of nurse practitioners (NPs) toward managed care and to identify the sources of negative attitudes and the factors that may ameliorate them. DATA SOURCES: NPs, members of the Massachusetts Coalition of NPs, participated in in-depth interviews about the impact of managed care on their practice. CONCLUSIONS: The sources of NP negativity about managed care for many study participants lay in their not appreciating the importance of the business aspects of practice and the provider's role in controlling healthcare costs, reluctance to work with what they perceived as a rigid "system," and lack of support for them to navigate it. They felt pressured by productivity issues, time constraints, practice restrictions, and documentation demands associated with reimbursement. Those who sustained a more positive attitude were realistic about healthcare economics, were willing and able to negotiate the system, were creative and flexible, and felt empowered by knowledge of the business of practice. Some NPs, however, chose to work in practices where they did not feel as pressured as their counterparts in large, busy primary care practices. IMPLICATIONS FOR NP PRACTICE AND EDUCATION: Understanding experiences that have influenced NP attitudes regarding managed care may assist NP faculty to better prepare NP students for their future roles. NPs must be able to challenge, yet be part of, an evolving system that promotes cost-effective health care for everyone, which was what managed care originally was intended to do. PMID- 17341281 TI - The utility of the Kohlman Evaluation of Living Skills test is associated with substantiated cases of elder self-neglect. AB - PURPOSE: Self-neglect is the most prevalent finding among cases reported to Adult Protective Services (APS) and is characterized by an inability to meet one's own basic needs. The Kohlman evaluation of living skills (KELS) has been validated in geriatric populations to assess performance with both instrumental and basic activities of daily living and as an assessment tool for the capacity to live independently; therefore, the purpose of this analysis was to compare the scores of the KELS between substantiated cases of self-neglect and matched community dwelling elders. DATA SOURCES: This is a cross-sectional pilot study of 50 adults aged 65 years and older who were recruited from APS as documented cases of self neglect and 50 control participants recruited from Harris County Hospital District outpatient clinics. Control participants were matched for age, race, gender, and ZIP code. A geriatric nurse practitioner (NP)-led team administered a comprehensive geriatric assessment in homes of all study participants. The assessment included the KELS and mini-mental state examination (MMSE) tests. Chi square analyses were used to determine if cases of self-neglect were significantly more likely to fail the KELS test than matched controls. CONCLUSIONS: The analyses revealed that self-neglectors were significantly more likely to fail the KELS than non-self-neglectors (50% vs. 30%, p = .025). When stratified by MMSE scores, self-neglectors with intact cognitive function remained significantly more likely to fail the KELS compared to matched, cognitively intact controls (45% vs. 17%, p = .013). Abnormal results using an in home KELS test were significantly associated with substantiated cases of self neglect. IMPLICATIONS FOR PRACTICE: There is currently no gold-standard measure for identifying capacity with self-care behaviors among cases of self-neglect. As a result, self-neglect may remain unidentified in many clinical settings. The KELS provides clinicians with an objective measure of an individual's capacity and performance with everyday life-supporting tasks and thus, provides information that can help NPs identify elders at risk for self-neglect. These findings suggest that the KELS test has significant utility as part of a comprehensive geriatric assessment to aid clinicians in suspected cases of self neglect. PMID- 17341283 TI - Treating vasomotor symptoms of menopause: the nurse practitioner's perspective. AB - PURPOSE: This article reviews the pathophysiology of vasomotor symptoms (VMS) of menopause and current management options. DATA SOURCES: Current scientific literature. CONCLUSIONS: In most menopausal women, loss of ovarian function results in VMS, including hot flashes, night sweats, and mood and sleep disturbances. Hormone therapy (HT) has been the mainstay of VMS treatment for many years, but safety concerns raised by publication of the Women's Health Initiative (WHI) results have dramatically reduced the use of this treatment. Since the WHI published its findings, attention has focused on other novel treatments for menopausal symptoms, including low-dose oral or transdermal HT and agents such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, and clonidine. Many women also use complementary and alternative medications to manage VMS, but little evidence from controlled clinical trials supports their efficacy. IMPLICATIONS FOR PRACTICE: The increasing number of alternative treatments for VMS requires improvement in patient-provider communication about treatment risks and benefits, individualization of treatment to meet patient needs and attitudes, and careful follow-up to ensure adherence to potentially effective therapy. Nurse practitioners play a leading role in patient evaluation, discussions, and management to help women achieve control over bothersome VMS that dramatically impact their quality of life. PMID- 17341284 TI - To be DR8 or not to be DQ8, that is the question. PMID- 17341285 TI - HLA-DRB1*08 allele may help to distinguish between type 1 diabetes mellitus and type 2 diabetes mellitus in Mexican children. AB - BACKGROUND: It may be difficult to distinguish type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) in the pediatric population. Autoantibodies may help to differentiate both types of diabetes, but sometimes these are positive in patients with T2DM and negative in patients with T1DM. The human leukocyte antigen (HLA)-DR genotype has been associated with T1DM and with T2DM only in adults and in determined cases. AIM: To determine the differences in HLA class II allele frequencies in Mexican children with T1DM and T2DM. METHODS: We included 72 children with T1DM, 28 children with T2DM, and 99 healthy controls. All were Mexican, and diabetes was diagnosed according to the clinical and laboratory criteria established by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. The HLA-DRB1 typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe and polymerase chain reaction sequence-specific primers. RESULTS: We found an increased frequency of HLA-DRB1*08 and a decreased frequency of HLA-DRB1*04 in the group with T2DM vs. T1DM [p = 0.0001, odds ratio (OR) = 10.58, 95% confidence interval (CI) = 3-40.8 and p = 0.0006, OR = 0.24, 95% CI = 0.11-0.53, respectively]. No significant differences were found between HLA-DRB1 alleles in T2DM vs. controls. In the group with T1DM, there was a significantly increased frequency of the HLA DR4 and HLA-DR3 alleles relative to controls (p = 0.0000001, OR = 3.59, 95% CI = 2.2-5.8 and p = 0.00009, OR = 4.66, 95% CI = 2.1-10.3, respectively). CONCLUSION: There are significant differences in the HLA profile in Mexican children with T1DM and T2DM. HLA typing could play a role in the differentiation between both types of diabetes in this population. PMID- 17341286 TI - Vitamin D supplementation and diabetes-related autoimmunity in the ABIS study. AB - Supplementation with vitamin D during infancy, as well as intake of vitamin D during pregnancy, has been associated with decreased risk of type 1 diabetes or diabetes-related autoantibodies in children. The primary aim of this report was to investigate whether vitamin D supplementation during infancy is associated with diabetes-related autoimmunity at 1 and 2.5 yr in the children. Second, we examined whether consumption of vitamin-D-containing supplements during pregnancy is related to risk of autoimmunity in the offspring. Screening questionnaires were completed for 16,070 infants after delivery, including a food-frequency questionnaire regarding the mother's use of dietary supplements during pregnancy. Parents of 11,081 and 8805 infants completed a follow-up questionnaire regarding the use of vitamin supplementation at 1 and 2.5 yr, respectively. Autoantibodies against glutamic acid decarboxylase and islet antigen-2 (IA-2) were analyzed in whole blood from 8694 children at 1 yr and 7766 children at 2.5 yr. Supplementation with AD-drops was not associated with autoantibodies at 1 or 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced diabetes-related autoimmunity at 1 yr (adjusted odds ratio: 0.707, confidence interval: 0.520-0.962, p = 0.028) but not at 2.5 yr. In conclusion, no association was found between an intermediate dose of vitamin D supplementation during infancy and development of diabetes-related autoantibodies at 1 and 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced development of glutamic acid decarboxylase autoantibodies or IA-2A in the offspring at 1 yr, but not at 2.5 yr. PMID- 17341287 TI - What is the frequency of symptomatic mild hypoglycemia in type 1 diabetes in the young?: assessment by novel mobile phone technology and computer-based interviewing. AB - BACKGROUND: The prevalence of mild hypoglycemia is difficult to document, particularly, in young people with diabetes. The usual method is to ask for subject recall using written 'diaries'. OBJECTIVE: In 2004, we investigated if new technology could be used to ascertain an accurate prevalence of mild hypoglycemia, particularly self-treated. We compared the use of 'text messaging' and computer-based interviewing with the standard diary method. PARTICIPANTS: Thirty-seven participants, aged 7-18 yr, with type 1 diabetes (T1D) for >1-yr duration. METHOD: Open comparison of three systems to collect the data on frequency of hypos (all severity): diary, mobile phone and computer-based interview (CBI), with qualitative analysis of patient feedback. RESULTS: One hundred thirty-two hypos were found over 705 recorded days. All were graded mild or moderate and none severe. Calculated frequency was 5.2 hypos per month: 13.6% subjects had no recorded episode, 36.4% had 1-4, 31.8% 5-9 and 18.2% >10. Mean blood glucose level at the onset of hypoglycemia was 3.0 mmol/L (1.0-5.2). Response rate of occurrence of hypoglycemic episode recorded by three systems is as follows - diary: 24 (65%) of the 37 subjects reported episodes, mobile: 18 (95%) of 19 subjects and CBI: 16 (89%) of 18 subjects. Sixty-five percent of subjects preferred the mobile and 54% of subjects preferred CBI compared with the diary. Fifty-five percent and 30.8% of subjects found the mobile and the CBI, respectively, easiest to fit into their everyday life. CONCLUSIONS: Mobile phone text messaging and CBI are alternatives to written diaries as methods of data collection. Each has its own strengths and weaknesses, but both have the advantage of daily reminders, rapid response and quick data analysis. Using this technology, it was found that the frequency of hypoglycemia was higher (>3 times) than that previously recognized. PMID- 17341288 TI - Psychometric properties of questionnaires measuring associations between behavioral factors and diabetes care for youth with type 2 diabetes. AB - BACKGROUND: Because of the recency of the large numbers of youth diagnosed with type 2 diabetes (T2D), measures of adherence behavior and family response to diabetes have not been developed or tested. OBJECTIVE: The objective of this study is to identify whether questionnaires on personal and family behaviors regarding the care of diabetes previously used with youth with type 1 diabetes (T1D) are reliable and related to metabolic control among youth with T2D. DESIGN/METHODS: During a regularly scheduled visit, youth with T2D and a parent/guardian were invited to participate in the study. Youth and a parent completed questionnaires and one 24-h dietary recall at the visit. During the following 2 wk, each youth completed two telephone dietary recalls and physical activity questionnaires. RESULTS: Child-reported scales measuring parental reminding, positive family behavior, self-care behaviors, and self-efficacy and maternal report of child self-care behaviors and maternal self-efficacy were found to have adequate internal consistency. Only parental reminding was related to metabolic control. Those youth reporting higher parental reminding were in poorer metabolic control. CONCLUSIONS: These scales appear to be reliable with youth with T2D in south Texas. PMID- 17341289 TI - Diabetic ketoacidosis. PMID- 17341290 TI - Phases of diabetes. PMID- 17341292 TI - Confirmation of double-peaked time distribution of mortality among Asian breast cancer patients in a population-based study. AB - INTRODUCTION: Double-peaked time distributions of the mortality hazard function have been reported for breast cancer patients from Western populations treated with mastectomy alone. These are thought to reflect accelerated tumour growth at micrometastatic sites mediated by angiogenesis after primary tumour removal as well as tumor dormancy. Similar data are not available for Asian populations. We sought to investigate whether differences exist in the pattern of mortality hazard function between Western breast cancer patients and their Asian counterparts in Singapore, which may suggest underlying differences in tumor biology between the two populations. METHODS: We performed a retrospective cohort study of female unilateral breast cancer patients diagnosed in Singapore between October 1994 and June 1999. Data regarding patient demographics, tumour characteristics and death were available. Overall survival curves were calculated using the Kaplan-Meier method. The hazard rate was calculated as the conditional probability of dying in a time interval, given that the patient was alive at the beginning of the interval. The life table method was used to calculate the yearly hazard rates. RESULTS: In the 2,105 women identified, 956 patients (45.4%) had mastectomy alone. Demographic characteristics were as follows: 86.5% were Chinese, 45.2% were postmenopausal, 38.9% were hormone receptor positive, 54.6% were node negative and 44.1% had high histological grade. We observed a double peaked mortality hazard pattern, with a first peak in mortality achieving its maximum between years 2 and 4 after mastectomy, and a second large peak in mortality during year 9. Analyses by subgroups revealed a similar pattern regardless of T stage, or node or menopausal status. This pattern was also noted in high-grade tumors but not in those that were well to moderately differentiated. The double-peaked pattern observed in Singaporean women was quantitatively and qualitatively similar to those reported in Western series. CONCLUSION: Our study confirms the existence of a double-peaked process in Asian patients, and it gives further support to the tumour dormancy hypothesis after mastectomy. PMID- 17341293 TI - Phase II study of two dose schedules of C.E.R.A. (Continuous Erythropoietin Receptor Activator) in anemic patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. AB - BACKGROUND: C.E.R.A. (Continuous Erythropoietin Receptor Activator) is an innovative agent with unique erythropoietin receptor activity and prolonged half life. This study evaluated C.E.R.A. once weekly (QW) or once every 3 weeks (Q3W) in patients with anemia and advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. METHODS: In this Phase II, randomized, open-label, multicenter, dose-finding study, patients (n = 218) with Stage IIIB or IV NSCLC and hemoglobin (Hb) or= 2 g/dL or achievement of Hb >or= 12 g/dL with no blood transfusion in the previous 28 days determined in two consecutive measurements within a 10 day interval) was also measured. RESULTS: Dose-dependent Hb increases were observed, although the magnitude of increase was moderate. Hematopoietic response rate was also dose dependent, achieved by 51% and 62% of patients in the 4.2 and 6.3 microg/kg Q3W groups, and 63% of the 2.1 mug/kg QW group. In the Q3W group, the proportion of early responders (defined as >or= 1 g/dL increase in Hb from baseline during the first 22 days) increased with increasing C.E.R.A. dose, reaching 41% with the highest dose. In the 6.3 microg/kg Q3W group, 15% of patients received blood transfusion. There was an inclination for higher mean Hb increases and lower transfusion use in the Q3W groups than in the QW groups. C.E.R.A. was generally well tolerated. CONCLUSION: C.E.R.A. administered QW or Q3W showed clinical activity and safety in patients with NSCLC. There were dose dependent increases in Hb responses. C.E.R.A. appeared to be more effective when the same dose over time was given Q3W than QW, with a suggestion that C.E.R.A. 6.3 microg/kg Q3W provided best efficacy in this study. However, further dose finding studies using higher doses are required to determine the optimal C.E.R.A. dose regimen in cancer patients receiving chemotherapy. PMID- 17341294 TI - Proximal-type epithelioid sarcoma--a rare, aggressive subtype of epithelioid sarcoma presenting as a recurrent perineal mass in a middle-aged male. AB - BACKGROUND: Epithelioid sarcoma (ES) is an uncommon soft tissue sarcoma. Lately, subtypes of ES, including proximal-type ES have been recognized, with relatively few reports on such cases. CASE PRESENTATION: A 47-year-old male presented with a perineal soft tissue mass that was excised elsewhere and the biopsy was submitted for a review diagnosis. On histology, a multi nodular tumor was seen comprising sheets of oval to polygonal cells with moderate amount of cytoplasm. Interspersed were larger, rhabdoid cells with abundant eosinophilic cytoplasm and prominent nucleoli. Focal necrosis was noted. A wide panel of immunohistochemical (IHC) markers was performed to rule out a range of differential diagnoses, including a poorly differentiated carcinoma, a melanoma and a variety of sarcomas with epithelioid differentiation. On IHC, the tumor cells showed a polyphenotypic expression, including positivity for epithelial markers i.e cytokeratin (CK), CK7, EMA and mesenchymal markers like vimentin and CD 34. Desmin was focally positive. CK20, CEA, S-100, HMB-45, SMA, LCA and CD31 were negative. A diagnosis of a proximal-type ES was formed. Six moths later, despite adjuvant chemo and radiotherapy (CT and RT), the patient continued to have the lesion and was referred again. In addition to the earlier histological features, sections from the persistent tumor mass showed an increased number of larger cells along with multinucleated tumor giant cells. CONCLUSION: The value of identifying this uncommon tumor from a list of differential diagnoses is in view of its aggressive behavior, as seen in our case. A wide excision with clear margins is imperative with options of post-operative CT/RT in individual cases during a close follow up. PMID- 17341295 TI - Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats. AB - BACKGROUND: Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Conversely, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. METHODS: Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C--pregnant control, W- tumour-bearing, and P--pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine rich diet: L--pregnant leucine, WL--tumour-bearing, and PL--pair-fed, which received the same amount of food as ingested by the WL group. RESULTS: The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2alpha and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. CONCLUSION: The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway. PMID- 17341296 TI - Time trends of chest pain symptoms and health related quality of life in coronary artery disease. AB - BACKGROUND: There is at present a lack of knowledge of time trends in health related quality of life (HRQL) in common patients with coronary artery disease (CAD) treated in ordinary care. The objective of this study is to assess and compare time trends of health related quality of life (HRQL) and chest pain in patients with coronary artery disease. METHODS: 253 consecutive CAD patients in Stockholm County, Sweden--197 males/56 females; 60 +/- 8 years--were followed during two years. Perceived chest pain symptoms and three global assessments of HRQL were assessed at baseline, after one and after two years. EuroQol-5 dimension (EQ-5D) with a predefined focus on function and symptoms; the broader tapping global estimates of HRQL; EuroQol VAS (EQ-VAS) and Cardiac Health Profile (CHP) were used. Chest pain was ranked according to Canadian Cardiovascular Society (CCS). Change in HRQL was analysed by a repeated measurements ANOVA and chest pain symptoms were analysed by Friedman non-parametric ANOVA. RESULTS: Perceived chest pain decreased during the two years (p < 0.00022); CCS 0: 41-51%; CCS 1: 19-15%; CCS 2: 31-27%; CCS 3: 5-4% and CCS 4: 4-2%. By contrast, HRQL did not change: EQ-5D: 0.76 (CI 0.73-0.79) -0.78 (CI 0.75-0.81), EQ-VAS: 0.68 (CI 0.66-0.71)-0.68 (CI 0.65-0.71) and CHP: 0.66 (CI 0.64-0.69) -0.66 (CI 0.64-0.69). CONCLUSION: HRQL did not increase despite a reduction in the severity of chest pain during two years. This implies that the major part of HRQL in these consecutive ordinary patients with CAD is unresponsive to change in chest pain symptoms. PMID- 17341297 TI - The Anopheles dirus complex: spatial distribution and environmental drivers. AB - BACKGROUND: The Anopheles dirus complex includes efficient malaria vectors of the Asian forested zone. Studies suggest ecological and biological differences between the species of the complex but variations within species suggest possible environmental influences. Behavioural variation might determine vector capacity and adaptation to changing environment. It is thus necessary to clarify the species distributions and the influences of environment on behavioural heterogeneity. METHODS: A literature review highlights variation between species, influences of environmental drivers, and consequences on vector status and control. The localisation of collection sites from the literature and from a recent project (MALVECASIA) produces detailed species distributions maps. These facilitate species identification and analysis of environmental influences. RESULTS: The maps give a good overview of species distributions. If species status partly explains behavioural heterogeneity, occurrence and vectorial status, some environmental drivers have at least the same importance. Those include rainfall, temperature, humidity, shade, soil type, water chemistry and moon phase. Most factors are probably constantly favourable in forest. Biological specificities, behaviour and high human-vector contact in the forest can explain the association of this complex with high malaria prevalence, multi-drug resistant Plasmodium falciparum and partial control failure of forest malaria in Southeast Asia. CONCLUSION: Environmental and human factors seem better than species specificities at explaining behavioural heterogeneity. Although forest seems essential for mosquito survival, adaptations to orchards and wells have been recorded. Understanding the relationship between landscape components and mosquito population is a priority in foreseeing the influence of land-cover changes on malaria occurrence and in shaping control strategies for the future. PMID- 17341298 TI - Is chloroquine chemoprophylaxis still effective to prevent low birth weight? Results of a study in Benin. AB - BACKGROUND: In areas of stable transmission, malaria during pregnancy is associated with severe maternal and foetal outcomes, especially low birth weight (LBW). To prevent these complications, weekly chloroquine (CQ) chemoprophylaxis is now being replaced by intermittent preventive treatment with sulfadoxine pyrimethamine in West Africa. The prevalence of placental malaria and its burden on LBW were assessed in Benin to evaluate the efficacy of weekly CQ chemoprophylaxis, prior to its replacement by intermittent preventive treatment. METHODS: In two maternity clinics in Ouidah, an observational study was conducted between April 2004 and April 2005. At each delivery, placental blood smears were examined for malaria infection and women were interviewed on their pregnancy history including CQ intake and dosage. CQ was measured in the urine of a sub sample (n = 166). Multiple logistic and linear regression were used to assess factors associated with LBW and placental malaria. RESULTS: Among 1090 singleton live births, prevalence of placental malaria and LBW were 16% and 17% respectively. After adjustment, there was a non-significant association between placental malaria and LBW (adjusted OR = 1.43; P = 0.10). Multiple linear regression showed a positive association between placental malaria and decreased birth weight in primigravidae. More than 98% of the women reported regular chemoprophylaxis and CQ was detectable in 99% of urine samples. Protection from LBW was high in women reporting regular CQ prophylaxis, with a strong duration effect relationship (test for linear trend: P < 0,001). CONCLUSION: Despite high parasite resistance and limited effect on placental malaria, a CQ chemoprophylaxis taken at adequate doses showed to be still effective in reducing LBW in Benin. PMID- 17341299 TI - SBMLeditor: effective creation of models in the Systems Biology Markup language (SBML). AB - BACKGROUND: The need to build a tool to facilitate the quick creation and editing of models encoded in the Systems Biology Markup language (SBML) has been growing with the number of users and the increased complexity of the language. SBMLeditor tries to answer this need by providing a very simple, low level editor of SBML files. Users can create and remove all the necessary bits and pieces of SBML in a controlled way, that maintains the validity of the final SBML file. RESULTS: SBMLeditor is written in JAVA using JCompneur, a library providing interfaces to easily display an XML document as a tree. This decreases dramatically the development time for a new XML editor. The possibility to include custom dialogs for different tags allows a lot of freedom for the editing and validation of the document. In addition to Xerces, SBMLeditor uses libSBML to check the validity and consistency of SBML files. A graphical equation editor allows an easy manipulation of MathML. SBMLeditor can be used as a module of the Systems Biology Workbench. CONCLUSION: SBMLeditor contains many improvements compared to a generic XML editor, and allow users to create an SBML model quickly and without syntactic errors. PMID- 17341300 TI - Gender and respiratory factors associated with dyspnea in chronic obstructive pulmonary disease. AB - RATIONALE: We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction. OBJECTIVES: Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients. METHODS: In a FEV1 % matched population of 100 men and women with COPD we measured: age, MMRC, FEV1, FVC, TLC, IC/TLC, PaO2, PaCO2, DLCO, Pimax, P0.1, Ti/Ttot, BMI, ffmi, 6MWD and VAS scale before and after the test, the Charlson score and the SGRQ. We estimated the association between these parameters and MMRC scores. Multivariate analysis determined the independent strength of those associations. RESULTS: MMRC correlated with: BMI (men:-0.29, p = 0.04; women:-0.28, p = 0.05), ffmi (men: 0.39, p = 0.01), FEV1 % (men:-0.64, p < 0.001; women:-0.29, p = 0.04), FVC % (men:-0.45, p = 0.001; women:-0.33, p = 0.02), IC/TLC (men:-0.52, p < 0.001; women: -0.27, p = 0.05), PaO2 (men:-0.59, p < 0.001), PaCO2 (men:0.27, p = 0.05), DLCO (men:-0.54, p < 0.001), P0.1/Pimax (men:0.46, p = 0.002; women:0.47, p = 0.005), dyspnea measured with the Visual Analog Scale before (men:0.37, p = 0.04; women:0.52, p = 0.004) and after 6MWD (men:0.52, p = 0.002; women:0.48, p = 0.004) and SGRQ total (men:0.50, p < 0.001; women:0.59, p < 0.001). Regression analysis showed that P0.1/Pimax in women (r2 = 0.30) and BMI, DLCO, PaO2 and P0.1/Pimax in men (r2 = 0.81) were the strongest predictors of MMRC scores. CONCLUSION: In mild to severe COPD patients attending a pulmonary clinic, P0.1/Pimax was the unique predictor of MMRC scores only in women. Respiratory factors explain most of the variations of MMRC scores in men but not in women. Factors other than the respiratory ones should be included in the evaluation of dyspnea in women with COPD. PMID- 17341301 TI - CTLA-4 +49A/G and CT60 gene polymorphisms in primary Sjogren syndrome. AB - CTLA-4 encodes cytotoxic T lymphocyte-associated antigen-4, a cell-surface molecule providing a negative signal for T-cell activation. CTLA-4 gene polymorphisms have been widely studied in connection with genetic susceptibility to various autoimmune diseases, but studies have led to contradictory results in different populations. This case-control study sought to investigate whether CTLA 4 CT60 and/or +49A/G polymorphisms were involved in the genetic predisposition to primary Sjogren syndrome (pSS). We analysed CTLA-4 CT60 and +49A/G polymorphisms in a first cohort of 142 patients with pSS (cohort 1) and 241 controls, all of Caucasian origin. A replication study was performed on a second cohort of 139 patients with pSS (cohort 2). In cohort 1, the CTLA-4 +49A/G*A allele was found on 73% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.036; odds ratio (OR) 1.41, 95% confidence interval (CI) 1.02 to 1.95). No difference in CTLA-4 CT60 allelic or genotypic distribution was observed between patients (n = 142) and controls (n = 241). In the replication cohort, the CTLA-4 +49A/G*A allele was found on 62% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.30; OR 0.85, 95% CI 0.63 to 1.16). Thus, the CTLA-4 +49A/G*A allele excess among patients from cohort 1 was counterbalanced by its under-representation in cohort 2. When the results from the patients in both cohorts were pooled (n = 281), there was no difference in CTLA-4 +49A/G allelic or genotypic distribution in comparison with controls. Our results demonstrate a lack of association between CTLA-4 CT60 or +49A/G polymorphisms and pSS. Premature conclusions might have been made if a replication study had not been performed. These results illustrate the importance of case-control studies performed on a large number of patients. In fact, sampling bias may account for some contradictory results previously reported for CTLA-4 association studies in autoimmune diseases. PMID- 17341302 TI - Quantitative evaluation and selection of reference genes in mouse oocytes and embryos cultured in vivo and in vitro. AB - BACKGROUND: Real-time PCR is an efficient tool to measure transcripts and provide valuable quantitative information on gene expression of preimplantation stage embryos. Finding valid reference genes for normalization is essential to interpret the real-time PCR results accurately, and understand the biological dynamics during early development. The use of reference genes also known as housekeeping genes is the most widely applied approach. However, the different genes are not systematically compared, and as a result there is no uniformity between studies in selecting the reference gene. The goals of this study were to compare a wide selection of the most commonly used housekeeping genes in mouse oocytes and preimplantation stage embryos produced under different culture conditions, and select the best stable genes for normalization of gene expression data. RESULTS: Quantitative real time PCR method was used to evaluate 12 commonly used housekeeping genes (Actb, Gapdh, H2afz, Hprt, Ppia, Ubc, Eef1e1, Tubb4, Hist2h2aa1, Tbp, Bmp7, Polr2a) in multiple individual embryos representing six different developmental stages. The results were analysed, and stable genes were selected using the geNorm software. The expression pattern was almost similar despite differences in the culture system; however, the transcript levels were affected by culture conditions. The genes have showed various stabilities, and have been ranked accordingly. CONCLUSION: Compared to earlier studies with similar objectives, we used a unique approach in analysing larger number of genes, comparing embryo samples derived in vivo or in vitro, analysing the expression in the early and late maternal to zygote transition periods separately, and using multiple individual embryos. Based on detailed quantification, pattern analyses and using the geNorm application, we found Ppia, H2afz and Hprt1 genes to be the most stable across the different stages and culture conditions, while Actb, the classical housekeeping gene, showed the least stability. We recommend the use of the geometric averages of those three genes for normalization in mouse preimplantation-stage gene expression studies. PMID- 17341303 TI - NF-kappaB mediates the transcription of mouse calsarcin-1 gene, but not calsarcin 2, in C2C12 cells. AB - BACKGROUND: The calsarcins comprise a novel family of muscle-specific calcineurin interaction proteins that play an important role in modulating both the function and substrate specificity of calcineurin in muscle cells. The expression of calsarcin-1 (CS-1) is restricted to slow-twitch skeletal muscle fibres, whereas that of both calsarcin-2 (CS-2) and calsarcin-3 (CS-3) is enriched in fast-twitch fibres. However, the transcriptional control of this selective expression has not been previously elucidated. RESULTS: Our real-time RT-PCR analyses suggest that the expression of CS-1 and CS-2 is increased during the myogenic differentiation of mouse C2C12 cells. Promoter deletion analysis further suggests that an NF kappaB binding site within the CS-1 promoter is responsible for the up-regulation of CS-1 transcription, but no similar mechanism was evident for CS-2. These findings are further supported by the results of EMSA analysis, as well as by overexpression and inhibition experiments in which NF-kappaB function was blocked by treatment with its inhibitor, PDTC. In addition, the overexpression of NFATc4 induces both the CS-1 and CS-2 promoters, whereas MEF2C only activates CS-1. CONCLUSION: Our present data suggest that NF-kappaB is required for the transcription of mouse CS-1 but not CS-2, and that the regulation of the calsarcins is mediated also by the NFAT and MEF2 transcription factors. These results provide new insights into the molecular mechanisms governing transcription in specific muscle fibre cells. The calsarcins may also serve as a valuable mechanistic tool to better understand the regulation of calcineurin signalling during muscle differentiation. PMID- 17341304 TI - Differential expression of RANK, RANK-L, and osteoprotegerin by synovial fluid neutrophils from patients with rheumatoid arthritis and by healthy human blood neutrophils. AB - Functional links between bone remodeling and the immune system in chronic inflammatory arthritis are mediated, in part, by the ligand of receptor activator of nuclear factor-kappa-B (RANK-L). Because neutrophils play a crucial role in chronic inflammation, the goal of this study was to determine whether proteins of the RANK/RANK-L pathway are expressed by synovial fluid (SF) neutrophils from patients with rheumatoid arthritis (RA) and to characterize this pathway in normal human blood neutrophils. The expression of RANK-L, osteoprotegerin (OPG), RANK, and tumor necrosis factor receptor-associated factor 6 (TRAF6) was determined by polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and cytofluorometry. RANK signaling was analyzed by the degradation of inhibitor of kappaB-alpha (I-kappaB-alpha). SF neutrophils from patients with RA express and release OPG and express the membrane-associated forms of RANK-L and RANK. In contrast, normal blood neutrophils express only the membrane-associated form of RANK-L. They do not express the mRNAs encoding OPG and RANK. SF neutrophils from RA patients and normal blood neutrophils release no soluble RANK-L. They express the mRNA for TRAF6. The expression of OPG and RANK by normal human blood neutrophils, however, can be induced by interleukin-4 + tumor necrosis factor-alpha and by SFs from patients with RA. In contrast, SFs from patients with osteoarthritis do not induce the expression of OPG and RANK. Moreover, the addition of RANK-L to normal blood neutrophils pretreated by SF from patients with RA decreased I-kappaB-alpha, indicating that RANK signaling by neutrophils stimulated with SF is associated with nuclear factor-kappa-B activation. In summary, RANK-L is expressed by inflammatory and normal neutrophils, unlike OPG and RANK, which are expressed only by neutrophils exposed to an inflammatory environment. Taken together, these results suggest that neutrophils may contribute to bone remodeling at inflammatory sites where they are present in significantly large numbers. PMID- 17341305 TI - Association of estrogen receptor-alpha and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment. AB - INTRODUCTION: Medroxyprogesterone acetate (MPA) induces estrogen receptor (ER) positive and progesterone receptor (PR)-positive ductal invasive mammary carcinomas in BALB/c mice. We sought to reproduce this MPA cancer model in C57BL/6 mice because of their widespread use in genetic engineering. Within this experimental setting, we studied the carcinogenic effects of MPA, the morphologic changes in mammary glands that are induced by MPA and progesterone, and the levels of ER and PR expression in MPA-treated and progesterone-treated mammary glands. Finally, we evaluated whether the differences found between BALB/c and C57BL/6 mouse strains were due to intrinsic differences in epithelial cells. METHODS: The carcinogenic effect of MPA was evaluated in C57BL/6 mice using protocols proven to be carcinogenic in BALB/c mice. In addition, BALB/c and C57BL/6 females were treated with progesterone or MPA for 1 or 2 months, and mammary glands were excised for histologic studies and for immunohistochemical and Western blot evaluation of ER and PR. Hormone levels were determined by radioimmunoassay. Isolated mammary epithelial cells were transplanted into cleared fat pads of 21-day-old female Swiss nu/nu mice or control congenic animals. RESULTS: MPA failed to induce mammary carcinomas or significant morphologic changes in the mammary glands of C57BL/6 mice. The expression of ER alpha and PR isoform A in virgin mice was surprisingly much higher in BALB/c than in C57BL/6 mammary glands, and both receptors were downregulated in progestin treated BALB/c mice (P < 0.05). PR isoform B levels were low in virgin control mice and increased after progestin treatment in both strains. ER-beta expression followed a similar trend. No differences in hormone levels were found between strains. Surprisingly, the transplantation of the epithelial mammary gland cells of both strains into the cleared fat pads of Swiss (nu/nu) mice abolished the mammary gland morphologic differences and the ER and PR differences between strains. CONCLUSION: C57BL/6 mammary glands are resistant to MPA-induced carcinogenesis and to hormone action. MPA and progesterone have different effects on mammary glands. Low ER-alpha and PR-A levels in untreated mammary glands may be associated with a low-risk breast cancer profile. Although we cannot at this time rule out the participation of other, untested factors, our findings implicate the stroma as playing a crucial role in the strain-specific differential hormone receptor expression and hormone responsiveness. PMID- 17341306 TI - Time to decide about risk-reducing mastectomy: a case series of BRCA1/2 gene mutation carriers. AB - BACKGROUND: The purpose of this research was to explore women's decision-making experiences related to the option of risk-reducing mastectomy (RM), using a case series of three women who are carriers of a BRCA1/2 gene mutation. METHODS: Data was collected in a pilot study that assessed the response of women to an information booklet about RM and decision-making support strategies. A detailed analysis of three women's descriptions of their decision-making processes and outcomes was conducted. RESULTS: All three women were carriers of a BRCA1/2 gene mutation and, although undecided, were leaning towards RM when initially assessed. Each woman reported a different RM decision outcome at last follow-up. Case #1 decided not to have RM, stating that RM was "too radical" and early detection methods were an effective strategy for dealing with breast cancer risk. Case #2 remained undecided about RM and, over time, she became less prepared to make a decision because she felt she did not have sufficient information about surgical effects. Case #3 had undergone RM by the time of her second follow-up interview and reported that she felt "a load off (her) mind now". CONCLUSION: RM decision making may shift over time and require decision support over an extended period. PMID- 17341307 TI - Expression of PPARalpha modifies fatty acid effects on insulin secretion in uncoupling protein-2 knockout mice. AB - AIMS/HYPOTHESIS: In uncoupling protein-2 (UCP2) knockout (KO) mice, protection of beta cells from fatty acid exposure is dependent upon transcriptional events mediated by peroxisome proliferator-activated receptor-alpha (PPARalpha). METHODS: PPARalpha expression was reduced in isolated islets from UCP2KO and wild type (WT) mice with siRNA for PPARalpha (siPPARalpha) overnight. Some islets were also cultured with oleic or palmitic acid, then glucose stimulated insulin secretion (GSIS) was measured. Expression of genes was examined by quantitative RT-PCR or immunoblotting. PPARalpha activation was assessed by oligonucleotide consensus sequence binding. RESULTS: siPPARalpha treatment reduced PPARalpha protein expression in KO and WT islets by >85%. In siPPARalpha-treated UCP2KO islets, PA but not OA treatment significantly decreased the insulin response to 16.5 mM glucose. In WT islets, siPPARalpha treatment did not modify GSIS in PA and OA exposed groups. In WT islets, PA treatment significantly increased UCP2 mRNA and protein expression. Both PA and OA treatment significantly increased PPARalpha expression in UCP2KO and WT islets but OA treatment augmented PPARalpha protein expression only in UCP2KO islets (p < 0.05). PA treatment induced carnitine palmitoyltransferase I, acyl CoA oxidase and malonyl CoA decarboxylase mRNA in UCP2KO islets. CONCLUSION: These data show that the negative effect of saturated fatty acid on GSIS is mediated by PPARalpha/UCP2. Knockout of UCP2 protects beta-cells from PA exposure. However, in the absence of both UCP2 and PPARalpha even a short exposure (24 h) to PA significantly impairs GSIS. PMID- 17341308 TI - On the reliability and validity of manual muscle testing: a literature review. AB - INTRODUCTION: A body of basic science and clinical research has been generated on the manual muscle test (MMT) since its first peer-reviewed publication in 1915. The aim of this report is to provide an historical overview, literature review, description, synthesis and critique of the reliability and validity of MMT in the evaluation of the musculoskeletal and nervous systems. METHODS: Online resources were searched including Pubmed and CINAHL (each from inception to June 2006). The search terms manual muscle testing or manual muscle test were used. Relevant peer reviewed studies, commentaries, and reviews were selected. The two reviewers assessed data quality independently, with selection standards based on predefined methodologic criteria. Studies of MMT were categorized by research content type: inter- and intraexaminer reliability studies, and construct, content, concurrent and predictive validity studies. Each study was reviewed in terms of its quality and contribution to knowledge regarding MMT, and its findings presented. RESULTS: More than 100 studies related to MMT and the applied kinesiology chiropractic technique (AK) that employs MMT in its methodology were reviewed, including studies on the clinical efficacy of MMT in the diagnosis of patients with symptomatology. With regard to analysis there is evidence for good reliability and validity in the use of MMT for patients with neuromusculoskeletal dysfunction. The observational cohort studies demonstrated good external and internal validity, and the 12 randomized controlled trials (RCTs) that were reviewed show that MMT findings were not dependent upon examiner bias. CONCLUSION: The MMT employed by chiropractors, physical therapists, and neurologists was shown to be a clinically useful tool, but its ultimate scientific validation and application requires testing that employs sophisticated research models in the areas of neurophysiology, biomechanics, RCTs, and statistical analysis. PMID- 17341310 TI - A SaTScan macro accessory for cartography (SMAC) package implemented with SAS software. AB - BACKGROUND: SaTScan is a software program written to implement the scan statistic; it can be used to find clusters in space and/or time. It must often be run multiple times per day when doing disease surveillance. Running SaTScan frequently via its graphical user interface can be cumbersome, and the output can be difficult to visualize. RESULTS: The SaTScan Macro Accessory for Cartography (SMAC) package consists of four SAS macros and was designed as an easier way to run SaTScan multiple times and add graphical output. The package contains individual macros which allow the user to make the necessary input files for SaTScan, run SaTScan, and create graphical output all from within SAS software. The macros can also be combined to do this all in one step. CONCLUSION: The SMAC package can make SaTScan easier to use and can make the output more informative. PMID- 17341309 TI - Determination of hemispheric emotional valence in individual subjects: a new approach with research and therapeutic implications. AB - BACKGROUND: Much has been theorized about the emotional properties of the hemispheres. Our review of the dominant hypotheses put forth by Schore, Joseph, Davidson, and Harmon-Jones on hemispheric emotional valences (HEV) shows that none are supported by robust data. Instead, we propose that individual's hemispheres are organized to have differing HEVs that can be lateralized in either direction. METHODS: Probe auditory evoked potentials (AEP) recorded during a neutral and an upsetting memory were used to assess HEV in 28 (20 F) right handed subjects who were either victims of childhood maltreatment (N = 12) or healthy controls. In a sub-population, we determined HEV by emotional response to lateral visual field stimulation (LVFS), in which vision is limited to one, then the other hemifield. We compare a number of morphometric and functional brain measures between individuals who have right-negative versus left-negative HEV. RESULTS: Using AEPs to determine HEV, we found 62% of controls and 67% of maltreated subjects had right negative HEV. There was a strong interaction between HEV-laterality and gender, which together accounted for 60% of individual variability in total grey matter volume (GMV). HEV-laterality was associated with differences in hippocampal volume, amygdala/hippocampal ratios, and measures of verbal, visual and global memory. HEV-laterality was associated also with different constellations of symptoms comparing maltreated subjects to controls. Emotional response to LVFS provided a convenient and complementary measure of HEV laterality that correlated significantly with the HEVs determined by AEPs. CONCLUSION: Our findings suggest that HEV-laterality, like handedness or gender, is an important individual difference with significant implications for brain and behavioral research, and for guiding lateralized treatments such as rTMS. PMID- 17341311 TI - Differential response of lymphatic, venous and arterial endothelial cells to angiopoietin-1 and angiopoietin-2. AB - BACKGROUND: The lymphatic system complements the blood circulatory system in absorption and transport of nutrients, and in the maintenance of homeostasis. Angiopoietins 1 and 2 (Ang1 and Ang2) are regulators of both angiogenesis and lymphangiogenesis through the Tek/Tie-2 receptor tyrosine kinase. The response of endothelial cells to stimulation with either Ang1 or Ang2 is thought to be dependent upon the origin of the endothelial cells. In this study, we examined the effects of the angiopoietins on lymphatic, venous and arterial primary endothelial cells (bmLEC, bmVEC and bmAEC, respectively), which were isolated and cultured from bovine mesenteric vessels. RESULTS: BmLEC, bmVEC and bmAEC cell populations all express Tie-2 and were shown to express the appropriate cellular markers Prox-1, VEGFR3, and Neuropilin-1 that define the particular origin of each preparation. We showed that while bmLECs responded slightly more readily to angiopoietin-2 (Ang2) stimulation, bmVECs and bmAECs were more sensitive to Ang1 stimulation. Furthermore, exposure of bmLECs to Ang2 induced marginally higher levels of proliferation and survival than did exposure to Ang1. However, exposure to Ang1 resulted in higher levels of migration in bmLECs than did to Ang2. CONCLUSION: Our results suggest that although both Ang1 and Ang2 can activate the Tie-2 receptor in bmLECs, Ang1 and Ang2 may have distinct roles in mesenteric lymphatic endothelial cells. PMID- 17341312 TI - The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse. AB - BACKGROUND: The hematopoietic stem cells (HSCs) niche of the bone marrow is comprised of HSCs, osteoblasts, endothelial cells and a stromal component of non hematopoietic multipotent cells of mesenchymal origin named "mesenchymal stem cells" (MSCs). RESULTS: Here we studied the global transcriptional profile of murine MSCs with immuno-therapeutic potential and compared it with that of 486 publicly available microarray datasets from 12 other mouse tissues or cell types. Principal component analysis and hierarchical clustering identified a unique pattern of gene expression capable of distinctively classifying MSCs from other tissues and cells. We then performed an analysis aimed to identify absolute and relative abundance of transcripts in all cell types. We found that the set of transcripts uniquely expressed by MSCs is enriched in transcription factors and components of the Wnt signaling pathway. The analysis of differentially expressed genes also identified a set of genes specifically involved in the HSC niche and is complemented by functional studies that confirm the findings. Interestingly, some of these genes play a role in the maintenance of HSCs in a quiescent state supporting their survival and preventing them from proliferating and differentiating. We also show that MSCs modulate T cell functions in vitro and, upon in vivo administration, ameliorate experimental autoimmune encephalomyelitis (EAE). CONCLUSION: Altogether, these findings provide novel and important insights on the mechanisms of T cell function regulation by MSCs and help to cement the rationale for their application in the treatment of autoimmune diseases. PMID- 17341313 TI - Neurturin enhances the recovery of erectile function following bilateral cavernous nerve crush injury in the rat. AB - BACKGROUND: The molecular mechanisms responsible for the survival and preservation of function for adult parasympathetic ganglion neurons following injury remain incompletely understood. However, advances in the neurobiology of growth factors, neural development, and prevention of cell death have led to a surge of clinical interest for protective and regenerative neuromodulatory strategies, as surgical therapies for prostate, bladder, and colorectal cancers often result in neuronal axotomy and debilitating loss of sexual function or continence. In vitro studies have identified neurturin, a glial cell line-derived neurotrophic factor, as a neuromodulator for pelvic cholinergic neurons. We present the first in vivo report of the effects of neurturin upon the recovery of erectile function following bilateral cavernous nerve crush injury in the rat. METHODS: In these experiments, groups (n = 8 each) consisted of uninjured controls and animals treated with injection of albumin (blinded crush control group), extended release neurotrophin-4 or neurturin to the site of cavernous nerve crush injury (100 mug per animal). After 5 weeks, recovery of erectile function (treatment effect) was assessed by cavernous nerve electrostimulation and peak aortic pressures were measured. Investigators were unblinded to specific treatments after statistical analyses were completed. RESULTS: Erectile dysfunction was not observed in the sham group (mean maximal intracavernous pressure [ICP] increase of 117.5 +/- 7.3 cmH2O), whereas nerve injury and albumin treatment (control) produced a significant reduction in ICP elevation of 40.0 +/- 6.3 cmH2O. Neurturin facilitated the preservation of erectile function, with an ICP increase of 55% at 62.0 +/- 9.2 cmH2O (p < 0.05 vs control). Extended release neurotrophin-4 did not significantly enhance recovery of erectile function with an ICP change of 46.9 +/- 9.6. Peak aortic blood pressures did not differ between groups. No significant pre- and post-treatment weight differences were observed between control, neurotrophin-4 and neurturin cohorts. All animals tolerated the five-week treatment course. CONCLUSION: Treatment with neurturin at the site of cavernous nerve crush injury facilitates recovery of erectile function. Results support further investigation of neurturin as a neuroprotective and/or neuroregenerative agent facilitating functional recovery after cavernous or other pelvic autonomic nerve injuries. PMID- 17341315 TI - Policy on infant formula industry funding, support or sponsorship of articles submitted for publication. AB - Despite current scientific evidence that artificial feeding is a harmful practice, unquestioned acceptance of breastfeeding as the normal or "default" method of infant feeding remains elusive in the industrialised world. Throughout the developing world the profound consequences of the aggressive marketing strategies of the infant formula industry since the end of the Second World War is well known. A key objective of the International Breastfeeding Journal is to promote breastfeeding through addressing issues that encourage breastfeeding initiation, duration and effective management. Informing this aim is the recognition of artificial feeding as a harmful practice that places infant health at risk. From this perspective it would be unethical for this journal to accept for publication any manuscript that has received funding, sponsorship or any other means of support from infant formula manufacturers. This stance is consistent with the journal's aim of supporting, protecting and promoting breastfeeding. It will also contribute to the promotion of a breastfeeding culture. PMID- 17341314 TI - A bootstrap based analysis pipeline for efficient classification of phylogenetically related animal miRNAs. AB - BACKGROUND: Phylogenetically related miRNAs (miRNA families) convey important information of the function and evolution of miRNAs. Due to the special sequence features of miRNAs, pair-wise sequence identity between miRNA precursors alone is often inadequate for unequivocally judging the phylogenetic relationships between miRNAs. Most of the current methods for miRNA classification rely heavily on manual inspection and lack measurements of the reliability of the results. RESULTS: In this study, we designed an analysis pipeline (the Phylogeny-Bootstrap Cluster (PBC) pipeline) to identify miRNA families based on branch stability in the bootstrap trees derived from overlapping genome-wide miRNA sequence sets. We tested the PBC analysis pipeline with the miRNAs from six animal species, H. sapiens, M. musculus, G. gallus, D. rerio, D. melanogaster, and C. elegans. The resulting classification was compared with the miRNA families defined in miRBase. The two classifications were largely consistent. CONCLUSION: The PBC analysis pipeline is an efficient method for classifying large numbers of heterogeneous miRNA sequences. It requires minimum human involvement and provides measurements of the reliability of the classification results. PMID- 17341316 TI - Application and investigation of a bound for outcome reporting bias. AB - BACKGROUND: Direct empirical evidence for the existence of outcome reporting bias is accumulating and this source of bias is recognised as a potential threat to the validity of meta-analysis of randomised clinical trials. METHODS: A method for calculating the maximum bias in a meta-analysis due to publication bias is adapted for the setting where within-study selective non-reporting of outcomes is suspected, and compared to the alternative approach of missing data imputation. The properties of both methods are investigated in realistic small sample situations. RESULTS: The results suggest that the adapted Copas and Jackson approach is the preferred method for reviewers to apply as an initial assessment of robustness to within-study selective non-reporting. CONCLUSION: The Copas and Jackson approach is a useful method for systematic reviewers to apply to assess robustness to outcome reporting bias. PMID- 17341317 TI - Overcoming beta-agonist tolerance: high dose salbutamol and ipratropium bromide. Two randomised controlled trials. AB - BACKGROUND: Asthmatics treated with long-acting beta-agonists have a reduced bronchodilator response to moderate doses of inhaled short acting beta-agonists during acute bronchoconstriction. It is not known if the response to higher doses of nebulised beta-agonists or other bronchodilators is impaired. We assessed the effect of long-acting beta-agonist treatment on the response to 5 mg nebulised salbutamol and to ipratropium bromide. METHODS: Two double-blind, placebo controlled, crossover studies of inhaled formoterol 12 mug twice daily in patients with asthma.High-dose salbutamol: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 5 mg was then administered via nebuliser and the FEV1 was monitored for 20 minutes. Ipratropium: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled 4.5% saline to produce a 20% fall in FEV1. Salbutamol 200 mug or ipratropium bromide 40 mug was then inhaled and the FEV1 was monitored for 30 minutes. Four study arms compared the response to each bronchodilator after formoterol and placebo. Analyses compared the area under the bronchodilator response curves, adjusting for changes in pre-challenge FEV1, dose of provocational agent and FEV1 fall during the challenge procedure. RESULTS: The response to nebulised salbutamol was 15% lower after formoterol therapy compared to placebo (95% confidence 5 to 25%, p = 0.008). The response to ipratropium was unchanged. CONCLUSION: Long-acting beta agonist treatment induces tolerance to the bronchodilator effect of beta agonists, which is not overcome by higher dose nebulised salbutamol. However, the bronchodilator response to ipratropium bromide is unaffected. PMID- 17341318 TI - Antagonistic interaction of HIV-1 Vpr with Hsf-mediated cellular heat shock response and Hsp16 in fission yeast (Schizosaccharomyces pombe). AB - BACKGROUND: Expression of the HIV-1 vpr gene in human and fission yeast cells displays multiple highly conserved activities, which include induction of cell cycle G2 arrest and cell death. We have previously characterized a yeast heat shock protein 16 (Hsp16) that suppresses the Vpr activities when it is overproduced in fission yeast. Similar suppressive effects were observed when the fission yeast hsp16 gene was overexpressed in human cells or in the context of viral infection. In this study, we further characterized molecular actions underlying the suppressive effect of Hsp16 on the Vpr activities. RESULTS: We show that the suppressive effect of Hsp16 on Vpr-dependent viral replication in proliferating T-lymphocytes is mediated through its C-terminal end. In addition, we show that Hsp16 inhibits viral infection in macrophages in a dose-dependent manner. Mechanistically, Hsp16 suppresses Vpr activities in a way that resembles the cellular heat shock response. In particular, Hsp16 activation is mediated by a heat shock factor (Hsf)-dependent mechanism. Interestingly, vpr gene expression elicits a moderate increase of endogenous Hsp16 but prevents its elevation when cells are grown under heat shock conditions that normally stimulate Hsp16 production. Similar responsive to Vpr elevation of Hsp and counteraction of this elevation by Vpr were also observed in our parallel mammalian studies. Since Hsf mediated elevation of small Hsps occurs in all eukaryotes, this finding suggests that the anti-Vpr activity of Hsps is a conserved feature of these proteins. CONCLUSION: These data suggest that fission yeast could be used as a model to further delineate the potential dynamic and antagonistic interactions between HIV 1 Vpr and cellular heat shock responses involving Hsps. PMID- 17341319 TI - Pleomorphic adenocarcinoma of the lacrimal gland with multiple intracranial and spinal metastases. AB - BACKGROUND: Pleomorphic adenoma of the lacrimal gland is known to undergo malignant transformation when incompletely excised. Even if such a malignant change occurs, intracranial direct invasion and leptomeningeal seeding are seldom encountered. CASE PRESENTATION: A 50-year-old woman presented with malignant transformation associated with both intracranial invasion and multiple intracranial and spinal disseminations in the third recurrence of pleomorphic adenoma of the lacrimal gland, 6 years after initial treatment. MRI demonstrated increased extent of orbital mass, extending to the cavernous sinus. The patient underwent intensity-modulated radiation therapy (IMRT) and Gamma Knife radiosurgery. Follow-up MRI showed multiple leptomeningeal disseminations to the intracranium and spine. CONCLUSION: It is important to recognize that leptomeningeal intracranial and spinal disseminations of pleomorphic adenocarcinoma can occur, although it is extremely rare. To our knowledge, we report the first case of pleomorphic adenocarcinoma of the lacrimal gland presumably metastasizing to the intracranium and spine. PMID- 17341320 TI - Contribution of the suprachiasmatic nucleus to the formation of a time memory for heat exposure in rats. AB - We have reported that after rats were acclimated to heat for about 5 h daily at a fixed time, the pattern of day-night variations of core temperature (T(cor)) altered, i.e., their T(cor) fell, especially during the period when they had previously been exposed to heat. The suprachiasmatic nucleus (SCN) of the hypothalamus is known to be indispensable for the genesis of circadian rhythms of T(cor). We therefore investigated the involvement of the SCN in the characteristic fall in T(cor) in heat-acclimated rats. The rats were exposed to an ambient temperature of 33 degrees C only in the last half of the dark phase for 10 consecutive days. After the heat exposure schedule, the nocturnal pattern of T(cor) variations and Fos expression in the dorsomedial SCN altered so that the T(cor) and the number of Fos immunoreactive cells decreased in the last half of the dark phase. The bilateral lesions of the SCN of rats were made electrically, and the electrical lesions of the SCNs abolished the daily cycle of T(cor). In the SCN-lesioned rats, theT(cor) levels were significantly lowered after the 10-day heat exposure schedule. However, their T(cor) did not specifically drop during the period when they had previously been exposed to heat. These findings suggest that the SCN is crucial for establishing a time memory for heat stress, and it plays a minimal role in heat acclimation-induced changes in T(cor) in rats. PMID- 17341326 TI - [Health care costs of persons with diabetes prior to and following hospitalization in Argentina]. AB - OBJECTIVE: To analyze and compare the ambulatory care expenditures for persons with diabetes during prehospitalization and posthospitalization periods with those of diabetics who were not hospitalized for diabetes-related illnesses during the same period. METHODS: We determined the hospitalization and ambulatory care expenses incurred by an Argentine health insurer for the hospitalization of diabetic clients during the study period, and compared these expenses to the expenses of insured diabetics who were not hospitalized during that period. RESULTS: We identified 2,760 persons with diabetes (2.4% of the total number of persons covered by the insurance company). Of those, 1,683 (59%) were on medication for diabetes and its associated cardiovascular risk factors. Diabetes was associated with either one (41%) or two (24%) cardiovascular risk factors. Of those 1 683 persons, 102 (6%) were hospitalized for diabetes-related reasons during the study period. The frequency of hospitalization increased significantly in cases where diabetes was associated with arterial hypertension and dyslipidemia. Cardiovascular illness was the cause of 43.1% of the hospitalizations, with a significantly higher per capita cost than any of the other causes identified (mean +/- standard error of the mean: US 1,673 dollars +/ US 296.8 dollars; P < 0.05). The total annual per capita cost for health care for the diabetics who had been hospitalized was greater than for those who had not (US 2,907.8 dollars +/- US 262.5 dollars compared to US 473.4 dollars +/- US 9.8 dollars, respectively; P < 0.01). While the total posthospitalization ambulatory care expenditures were 12% higher than the prehospitalization costs (US 903.6 dollars +/- US 108.6 dollars vs. US 797.6 dollars +/- US 14.9 dollars), the difference was not significant. CONCLUSION: Ambulatory care expenditures increase significantly in the prehospitalization and posthospitalization periods. The results suggest that intensive treatment of hyperglycemia and its associated cardiovascular risk factors may prevent hospitalization and is a more cost effective option than hospitalization and posthospitalization ambulatory care. PMID- 17341327 TI - A case-control study of microenvironmental risk factors for urban visceral leishmaniasis in a large city in Brazil, 1999-2000. AB - OBJECTIVES: We investigated potential microenvironmental risk factors for visceral leishmaniasis in urban and suburban areas, and developed risk scores to characterize the household and the neighborhood. These scores may be useful to identify microenvironments within cities that place residents at greater risk of visceral leishmaniasis. METHODS: In this case-control study, cases were all persons with visceral leishmaniasis reported from July 1999 through December 2000 in the Belo Horizonte metropolitan area, Brazil. Two kinds of controls neighborhood and hospital-were used. Cases and controls were matched by age (+/-2 years). We developed four scores to characterize the microenvironment (indoor, outdoor, animal indoor, and animal outdoor), and also considered the level of urbanization of the area. RESULTS: A total of 106 neighborhood controls and 60 hospital controls were identified for 109 cases. Among the cases, 69 (63.3%) were men and 40 (36.7%) were women. Most cases were under 15 years old (64.2%), and 39 (35.8%) were 15 years old or more. The outdoor score [odds ratio (OR) = 1.49; 95% confidence interval (CI) = 1.03-2.14] and animal outdoor scores (OR = 1.79[95% CI 1.21-2.65]) were significantly associated with the odds of visceral leishmaniasis in our sample. We also found a significant interaction between sex and age. Compared to females 15 years old or more, males 15 years old or more were more likely to have visceral leishmaniasis (OR = 7.02[95% CI 2.20-22.20]). CONCLUSIONS: Animals in the neighborhood were associated with a greater odds of visceral leishmaniasis. Cases were more likely than controls to live in transitional or rural areas, although this difference was not statistically significant, possibly because of the small sample size. PMID- 17341328 TI - Burden of diarrhea among children in Honduras, 2000-2004: estimates of the role of rotavirus. AB - OBJECTIVES: To estimate the annual burden of diarrhea and of diarrhea that is associated with rotavirus (RV) in children who are treated at public clinics and hospitals in Honduras. METHODS: Data were collected from computerized records of all children < 5 years old treated for diarrhea at clinics and hospitals operated by the Secretary of Health for the period of 2000 through 2004. A review of studies of RV in Honduras and neighboring countries provided estimates of detection rates of RV among children treated for acute diarrhea as outpatients or as inpatients. From these data, we estimated the annual number of cases of diarrhea and of rotavirus-related diarrhea in Honduras, the cumulative incidence of diarrhea and of rotavirus-related diarrhea for a child from birth to age 5 years, and the number of fatalities due to RV among children hospitalized for diarrhea. RESULTS: From 2000 through 2004, a mean of 222,000 clinic visits, 4,390 hospitalizations, and 162 in-hospital deaths due to diarrhea were recorded annually among children < 5 years of age in the public health facilities in Honduras. From our review of scientific literature on Honduras and neighboring countries, an estimated 30% of outpatients and 43% of inpatients who were treated for diarrhea would be expected to have RV. Consequently, we estimated that 66,600 outpatient visits, 1,888 hospitalizations, and 70 in-hospital deaths among children < 5 years in Honduras could be attributed to RV each year. Therefore, a child in the first five years of life has a respective risk for consultation, hospitalization, and in-hospital death of 1:1, 1:46, and 1:1,235 for diarrhea. For an episode associated with RV, the respective risks are 1:3, 1:106, and 1:2,857. These values likely underestimate the true burden of diarrhea in Honduras, since some 51% of children with acute diarrhea do not receive formal care for the illness, 70% do not receive oral rehydration solution, and 80% of diarrheal deaths occur outside of hospitals. CONCLUSIONS: Diarrhea is a major cause of illness among children < 5 years old in Honduras, and RV is likely the most common cause. Our preliminary estimates need to be refined so that health planners in Honduras can make decisions on the future use of rotavirus vaccines. A program of hospital-based surveillance for rotavirus in Honduras has been established to address this need. PMID- 17341329 TI - [Risk analysis of nitrate contamination in wells supplying drinking water in a rural area of Chile]. AB - OBJECTIVES: To assess the risk associated with nitrate contamination of wells that supply drinking water in the rural, Parral region of central Chile. METHODS: The nitrate concentration levels were determined using water samples from 94 wells. An analysis of the distribution of nitrate concentration levels was performed in order to assess possible geographic correlations. For the risk analysis, two exposure situations were identified among the population (for adults and for infants), and the health risks were mapped. RESULTS: Fourteen percent of the wells studied had nitrate concentration levels greater than what the Chilean health standards allow for drinking water. There was no geographic correlation for the nitrate concentration levels. The mean hazard quotient (HQ) for adults in the study area was 0.12, indicating an absence of risk for this population group. For infants, the HQ values had a maximum value of 3.1 in some locations, but the average was 0.69 (still below 1.0), indicating that the well water in the study area was generally not hazardous for infants. CONCLUSIONS: In the Parral region of Chile, nitrate contamination of wells is primarily linked to certain factors such as construction practices and the proximity of livestock. These factors affect the quality of drinking water in isolated cases. There was no risk found for the adult population, but there was for infants fed on formula mixed with water coming from the contaminated wells. PMID- 17341330 TI - [Controlling diabetes mellitus and its complications in Medellin, Colombia, 2001 2003]. AB - OBJECTIVES: To identify the principal sociodemographic, clinical, and behavioral characteristics of patients participating in diabetic care programs in the city of Medellin, Colombia, and to evaluate progress toward the goal of metabolic control and diabetic care standards. METHODS: A cross-sectional, descriptive study was done, analyzing the clinical records of patients who had been participating for at least 6 months in the diabetic care programs of nine health care centers in Medellin. The study period ran from January 2001 to December 2003. The following data were collected: sociodemographic (age and sex), clinical (time since disease onset, diabetes type and treatment, and concurrent illnesses and their treatment), lifestyle habits (exercise routine, smoking, and sugar and fat consumption), chronic complications, and laboratory test results from the prior year. Questionable or missing data were categorized as unavailable. RESULTS: Of the 3 583 clinical histories evaluated, we were able to confirm the form of diabetes for 3 554 patients. Of those 3 554, 95.1% had type 2 diabetes. Overall, 56.9% (95% confidence interval (95% CI): 55.2% to 58.6%) of the patients exercised regularly, 15.1% (95% CI: 13.9% to 16.3%) were current smokers, 17.7% (95% CI: 16.4% to 19.0%) were former smokers, and 67.2% (95% CI: 65.6% to 68.8%) had never smoked. In all, 21.0% (95% CI: 19.6% to 22.5%) of the patients consumed sugar regularly, while 24.8% (95% CI: 23.3% to 26.3%) consumed fats and only 19.5% (95% CI: 17.8% to 21.3%) were self-monitoring their glucose levels at least weekly. Among the type 2 diabetics, 68.8% had high blood pressure, and 98.2% had dyslipidemia. The average body mass index was 28.0 kg/m(2) (95% CI: 27.8 to 28.2). The average number of medications that the patients were taking to treat type 2 diabetes was 1.3; to treat high blood pressure, 1.9; and to treat dyslipidemia, 0.6. There were no data on low-density lipoprotein (LDL) cholesterol in 44.8% of the clinical records, and no data on high-density lipoprotein (HDL) cholesterol in 16.4% of the records. Among the complications, the most common were ocular ones (31.8%; 95% CI: 30.1% to 33.5%), followed by renal ones (25.9%; 95% CI: 24.4% to 27.5%), and cardiovascular ones (22.5%; 95% CI: 21.1% to 23.8%). Cholesterol control achievement was inadequate for LDL (reached by only 14.2% of the patients), for triglycerides (36.9% of patients), and HDL (47.4% of patients). CONCLUSIONS: Among the study population in Medellin, the three chronic complications with the greatest impact on prognosis and health care costs of the diabetics were nephropathy, retinopathy, and dyslipidemia. The noticeable amount of unavailable data in the clinical records could be greatly reduced by standardizing the clinical record forms and by periodic quality checks of the records themselves. PMID- 17341331 TI - Evaluating in-home water purification methods for communities in Texas on the border with Mexico. AB - This study evaluated user preferences among three alternative in-home water treatment technologies suitable for households relying on trucked water in El Paso County, Texas, which is on the border with Mexico. The three technologies were: chlorination of household storage tanks, small-scale batch chlorination, and point-of-use ultraviolet disinfection. Fifteen households used each of the three technologies in succession for roughly four weeks each during April through June of 2004. Data were collected on treated water quality, and a face-valid survey was administered orally to assess user satisfaction with the technologies on a variety of attributes. Treatment with a counter-top ultraviolet disinfection system received statistically significantly higher ratings for taste and odor and likelihood of future use than the other two approaches. Ultraviolet disinfection and small-scale batch chlorination both received significantly higher ratings for ease of use than did storage tank chlorination. Over-chlorination was a common problem with both batch chlorination and storage tank chlorination. Water quality in the households using trucked water is now higher than was reported by a previous study, suggesting that water quality has improved over time. PMID- 17341332 TI - Dengue in the Americas and Southeast Asia: do they differ? AB - The populations of Southeast Asia (SE Asia) and tropical America are similar, and all four dengue viruses of Asian origin are endemic in both regions. Yet, during comparable 5-year periods, SE Asia experienced 1.16 million cases of dengue hemorrhagic fever (DHF), principally in children, whereas in the Americas there were 2.8 million dengue fever (DF) cases, principally in adults, and only 65,000 DHF cases. This review aims to explain these regional differences. In SE Asia, World War II amplified Aedes aegypti populations and the spread of dengue viruses. In the Americas, efforts to eradicate A. aegypti in the 1940s and 1950s contained dengue epidemics mainly to the Caribbean Basin. Cuba escaped infections with the American genotype dengue-2 and an Asian dengue-3 endemic in the 1960s and 1970s. Successive infections with dengue-1 and an Asian genotype dengue-2 resulted in the 1981 DHF epidemic. When this dengue-2 virus was introduced in other Caribbean countries, it encountered populations highly immune to the American genotype dengue-2. During the 1980s and 1990s, rapidly expanding populations of A. aegypti in Brazil permitted successive epidemics of dengue-1, 2, and -3. These exposures, however, resulted mainly in DF, with surprisingly few cases of DHF. The absence of high rates of severe dengue disease in Brazil, as elsewhere in the Americas, may be partly explained by the widespread prevalence of human dengue resistance genes. Understanding the nature and distribution of these genes holds promise for containing severe dengue. Future research on dengue infections should emphasize population-based designs. PMID- 17341333 TI - [Paradoxes of health decentralization policies in Brazil]. AB - The constitution of Brazil directs that the country's health system, the Unified Health System (Sistema Unico de Saude), be politically and administratively decentralized. Nevertheless, handing over competencies, responsibilities, and resources to subnational levels, especially to municipal governments, has been a slow process, lasting almost two decades. Advances have been brought about by the Unified Health System, which, from a analytical perspective, is a public and universal system. Despite that, the decentralization process needs to overcome norms that keep all levels of management dependent on Brazil's federal Government. The subnational levels have consistently faced difficulties in performing their macromanagement functions with autonomy, especially when it comes to financing and to the establishment or organization of health care networks. Boldness and responsibility will be needed to prevent Brazil's health decentralization process from leading to fragmentation. New political agreements between different levels of government, with a reassignment of responsibilities and the enhancement of a culture of technical cooperation, are fundamental requisites to making the Unified Health System have a health policy that is truly public and universal. PMID- 17341372 TI - Oral rehabilitation of a completely edentulous epidermolysis bullosa patient with an implant-supported prosthesis: a clinical report. AB - This clinical report describes the rehabilitation of a completely edentulous 29 year-old man diagnosed with recessive dystrophic epidermolysis bullosa (EB). Four implants were placed in each arch, and metal-resin implant fixed complete dentures were fabricated for both arches. This treatment option appears to be favorable for EB patients, compared to other options involving removable prostheses, in that it causes less mechanical irritation to the oral mucosa. PMID- 17341373 TI - Forced eruption and implant treatment in posterior maxilla: a clinical report. AB - Periodontal disease can result in bone defects that surround periodontally compromised teeth. After the loss of those teeth, remaining defects may compromise successful treatment with dental implants. Forced eruption, induced by applying light orthodontic forces in the coronal direction, provides enhancement of the implant recipient site by enabling the extraction of the periodontally hopeless teeth. This report describes the use of forced eruption to promote the formation of new bone and soft tissue in the resorbed maxillary posterior region, followed by placement of an implant-supported fixed partial denture. PMID- 17341374 TI - Rhinorrhea triggered by an obturator prosthesis: a clinical report. AB - This clinical report describes an unusual cause of nasal leakage in a patient with an obturator prosthesis who had previously undergone a maxillectomy. The diagnosis of gustatory rhinorrhea was determined by eliminating other possible causes of rhinitis. Gustatory rhinorrhea has been described as a complication of a maxillectomy. PMID- 17341375 TI - Three-year treatment outcomes with three brands of implants placed in the posterior maxilla and mandible of partially edentulous patients. AB - STATEMENT OF PROBLEM: Survival rates of implants in posterior regions vary among clinical studies. Problems occur more often in the posterior segment of the maxilla due to proximity of the maxillary sinus and reduced quality or quantity of alveolar bone. PURPOSE: This clinical study evaluated the treatment outcomes of 3 brands of implants in the posterior maxillae and mandibles of 63 patients. Treatment outcomes of all implants were assessed according to implant type, location, patient gender, periodontal status, and prosthesis type. MATERIAL AND METHODS: A total of 203 implants-105 ITI (ITI), 53 Camlog (CAM), and 45 Frialit (FRI)-were placed in 63 patients (38 women, 25 men). One hundred twelve implants were located in the posterior mandible and 91 in the posterior maxilla. All implants were longer than 10 mm and had a diameter larger than 3.5 mm. Implants in the ITI group were placed in a 1-stage surgery. The CAM and FRI groups were treated with a 2-stage surgical protocol. Implants were not loaded until osseointegration was complete, which was determined clinically and radiographically. At that point, implants were restored with 50 single crowns and 81 fixed partial dentures (FPDs). While 11 FPDs connected implants to natural teeth, 70 FPDs were supported by implants only. Standardized radiographs were made, and clinical parameters were recorded at prosthesis insertion (baseline) and at each recall evaluation (6, 12, 24, and 36 months). Plaque index (PI), sulcus bleeding index (SBI), peri-implant probing depth (PD), and radiographic marginal bone loss (MBL) levels were recorded at baseline, along with any biological and mechanical complications. Repeated-measures ANOVA, Kruskal-Wallis test, Wilcoxon signed rank test, and paired samples tests were used for statistical analysis (alpha=.05). RESULTS: One implant was lost during the osseointegration period in 1 woman due to infection. The cumulative implant treatment outcome was 99.3%. At the 3-year recall, plaque accumulation was significantly higher than baseline scores (P=.01, Wilcoxon signed rank test). Eight percent of the patients presented>2 mm PD at 2-year recall. The influence of observation time was found to be significant for the mean MBL values between groups (P=.001). When MBL values were compared between groups, no significant differences were found. For 1 patient in the FRI group, abutment loosening was observed and both the crown and the abutment were replaced. Patient satisfaction in all groups was high. CONCLUSION: The 3 brands of implants evaluated in this study exhibited similar positive treatment outcomes after 3 years. PMID- 17341376 TI - Effect of abutment angulation on the strain on the bone around an implant in the anterior maxilla: a finite element study. AB - STATEMENT OF PROBLEM: Angled abutments are often used to restore dental implants placed in the anterior maxilla due to esthetic or spatial needs. The effect of abutment angulation on bone strain is unknown. PURPOSE: The purpose of the current study was to measure and compare the strain distribution on the bone around an implant in the anterior maxilla using 2 different abutments by means of finite element analysis. MATERIAL AND METHODS: Two-dimensional finite element models were designed using software (ANSYS) for 2 situations: (1) an implant with a straight abutment in the anterior maxilla, and (2) an implant with an angled abutment in the anterior maxilla. The implant used was 4x13 mm (MicroThread). The maxillary bone was modeled as type 3 bone with a cortical layer thickness of 0.5 mm. Oblique loads of 178 N were applied on the cingulum area of both models. Seven consecutive iterations of mesh refinement were performed in each model to observe the convergence of the results. RESULTS: The greatest strain was found on the cancellous bone, adjacent to the 3 most apical microthreads on the palatal side of the implant where tensile forces were created. The same strain distribution was observed around both the straight and angled abutments. After several iterations, the results converged to a value for the maximum first principal strain on the bone of both models, which was independent of element size. Most of the deformation occurred in the cancellous bone and ranged between 1000 and 3500 microstrain. Small areas of cancellous bone experienced strain above the physiologic limit (4000 microstrain). CONCLUSIONS: The model predicted a 15% higher maximum bone strain for the straight abutment compared with the angled abutment. The results converged after several iterations of mesh refinement, which confirmed the lack of dependence of the maximum strain at the implant-bone interface on mesh density. Most of the strain produced on the cancellous and cortical bone was within the range that has been reported to increase bone mass and mineralization. PMID- 17341377 TI - In vitro evaluation of the fracture resistance of anterior endodontically treated teeth restored with glass fiber and zircon posts. AB - STATEMENT OF PROBLEM: The published information is equivocal regarding the fracture resistance of endodontically treated teeth restored with fiber posts. Additionally, little is known about the biomechanical performance of glass fiber and zircon posts. PURPOSE: This in vitro study investigated the fracture resistance of anterior endodontically treated teeth prepared with a 2-mm ferrule, restored with glass fiber and zircon posts and composite resin cores or cast posts and cores. MATERIAL AND METHODS: Twelve matched pairs of teeth were obtained from 4 cadavers, and all were endodontically treated and prepared with a standardized 2-mm ferrule. According to a random number table, the 2 teeth from each matched pair were randomly divided into 2 groups. The test group consisted of 12 specimens restored with a glass fiber and zircon post (Fibio) and composite resin (Durafil) core. Twelve matching specimens restored with a nickel-chromium (NiCr) cast post and core served as the control. Specimens in both groups were cemented with resin cement (Panavia F). After cementation of cast NiCr complete crowns with zinc polycarboxylate cement (ShangChi), the specimens were loaded with an incremental static force at an angle of 135 degrees to the long axis of the root until failure occurred. A paired sample t test was used to compare the fracture resistance (N) of teeth restored with the 2 post-and-core systems (alpha=.05). RESULTS: The mean failure load of paired differences between the 2 groups was -261.3+/-237.3 N. The test group exhibited significantly lower failure loads than the control group (P=.004). All specimens displayed root fractures, most of which were oblique, with cracks initiating from the palatal cervical margin and propagating in a labial-apical direction. CONCLUSION: Within the limitations of this study, the teeth restored with glass fiber and zircon posts demonstrated significantly lower failure loads than those with cast NiCr post and cores. All specimens failed via root fractures. PMID- 17341379 TI - Effects of mandibular odontogenic keratocyst surgery and removable partial prostheses on masticatory performance. AB - STATEMENT OF PROBLEM: Surgical treatment of odontogenic keratocysts often results in tooth loss. However, information about the effects of different surgical methods and postoperative prosthetic therapy on masticatory performance is lacking. PURPOSE: The purpose of this study was to compare tooth loss following odontogenic keratocyst treatment by enucleation, segmental mandibulectomy with reconstruction, or marsupialization, and the resultant effect on masticatory performance with and without removable partial dentures (RPDs). MATERIAL AND METHODS: Patients with odontogenic keratocysts of the mandible were treated with either enucleation (n=33), segmental mandibulectomy and immediate autogenous bone reconstruction (n=18), or marsupialization in combination with secondary enucleation (n=9). Clinical and radiographic examinations were used to assess the number of teeth with cyst involvement preoperatively and the number of teeth lost following cyst treatment. Masticatory performance with peanuts was measured after cyst treatment both with and without an RPD. The differences in the number of the teeth involved preoperatively and lost postoperatively were compared among the 3 groups with a chi square test for trend. The absorbance value (reflecting masticatory performance) difference among the 3 groups preprosthesis and postprosthesis was analyzed using a 1-way analysis of variance (ANOVA), respectively. The pre- and postprosthetic comparison was made within each group, and a paired t test was used. Age was compared using 1-way ANOVA among 3 groups. Gender was compared using the chi square test (alpha=.05). RESULTS: Although the average number of teeth involved preoperatively with the cyst was similar among the 3 treatment groups, the number of teeth lost following marsupialization was significantly less than the number lost following enucleation or segmental mandibulectomy. Prior to provision of an RPD, mean masticatory performance (mean absorbance value of 0.36+/-0.08) in subjects receiving segmental mandibulectomy was significantly lower than for subjects receiving enucleation (0.52+/-0.15) or marsupialization (0.89+/-0.12) (P<.01). Provision of an RPD significantly increased masticatory performance in subjects who were treated by enucleation or segmental mandibulectomy (P<.01). CONCLUSION: Masticatory performance following odontogenic keratocyst surgery is related to the number of lost teeth, which is a function of the operative method used. Restoration with an RPD postoperatively may improve masticatory function when multiple teeth are lost following enucleation or segmental mandibulectomy. PMID- 17341380 TI - The use of customized implant frameworks with gingiva-colored composite resin to restore deficient gingival architecture. AB - This article describes a technique for fabricating cement-retained crowns over a customized gingiva-colored composite resin screw-retained implant infrastructure. This prosthetic design is not significantly influenced by unsuitable implant position, alignment, or angulation. Consequently, the cement-retained crowns can be reproduced in an esthetically and functionally appropriate morphology, regardless of where the screw-access openings are located in the infrastructure. PMID- 17341378 TI - Microtensile bond strength of dual-polymerizing cementing systems to dentin using different polymerizing modes. AB - STATEMENT OF THE PROBLEM: The effectiveness of bond strength using dual polymerizing cementing systems ([DCSs] defined as the combination of dual polymerizing bonding agents and resin cements) used with indirect restorations has not been evaluated when used solely with the autopolymerizing mode. PURPOSE: This study evaluated the in vitro microtensile bond strength (MTBS) of fourth- and fifth-generation DCSs with indirect composite restorations either light polymerized or autopolymerized. MATERIAL AND METHODS: Occlusal dentin surfaces of 48 human third molars were exposed and flattened. Teeth were assigned to 8 groups (n=6) according to the DCS and polymerizing modes: All-Bond2/Duolink (AB2), Optibond/Nexus2 (OPT), Bond1/Lute-it (B1), and Optibond Solo Dual Cure/Nexus2 (SOLO). Bonding agents were applied to dentin surfaces and left in the unpolymerized state. Resin cements were applied to prepolymerized resin discs (2 mm thick/Z250), which were subsequently bonded to the dentin surfaces. The restored teeth were light polymerized according to manufacturers' instructions (PP/XL 3000) or allowed to autopolymerize (AP). Restored teeth were stored in water at 37 degrees C for 24 hours and were both mesio-distally and bucco lingually sectioned to obtain multiple bonded beams (1.2 mm2 of cross-sectional area). Each specimen was tested in tension at a crosshead speed of 0.6 mm/min until failure. Data (MPa) were analyzed by 2-way analysis of variance and the Tukey post hoc test (alpha=.05). Failure patterns of tested specimens were analyzed using scanning electron microscopy. RESULTS: The mean (SD) MTBS values (MPa) were: AB2/PP: 36.9 (6.5); AB2/AP: 32.7 (7.3); B1/PP: 38.2 (7.0); B1/AP: 13.0 (4.2); SOLO/PP: 33.2 (7.2); SOLO/AP: 23.4 (3.4); OPT/PP: 30.8 (7.5); OPT/AP: 13.1 (5.8). The AP groups showed significantly lower MTBS than the PP groups (P<.0001), except for AB2, which showed no difference between polymerization modes (P=.2608). CONCLUSION: The autopolymerizing mode of some dual-polymerizing cement systems may not be effective in promoting bond strength. PMID- 17341381 TI - Achieving predictable gingival stippling in labial flanges of gingival veneers and complete dentures. PMID- 17341383 TI - Electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic ischemic heart disease. AB - BACKGROUND: Bone marrow cell injection has been introduced to treat patients with ischemic heart disease. However, focal application of bone marrow cells may generate an arrhythmogenic substrate. OBJECTIVES: To assess the electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia. METHODS: Bone marrow was aspirated in 20 patients (65+/-11 years, 19 male) with drug-refractory angina and myocardial ischemia. Electroanatomical mapping (NOGA, Biosense-Webster, Waterloo, Belgium) was performed during mononuclear cell isolation. Areas for cell injection were selected based on the localization of ischemia on SPECT. These areas were mapped in detail to evaluate local bipolar electrogram duration, amplitude and fragmentation. Mononuclear cells were injected in the ischemic area with the NOGA system. SPECT and electroanatomical mapping were repeated at 3 months. Holter monitoring was repeated at 3 and 6 months. RESULTS: SPECT revealed a decrease in the number of segments with ischemia (3.5+/-2.5 vs. 1.1+/-1.0 at 3 months; P<0.01) and an increased left ventricular ejection fraction (44+/-13% vs. 49+/-17% at 3 months; P=0.02). The number of ventricular premature beats remained unchanged (10+/-24x10(2)/24h vs. 8+/-23x10(2)/24h at 3 months (P=NS) and 12+/ 30x10(2)/24h at 6 months (P=NS)). At 3 months follow-up, bone marrow cell injection did not prolong electrogram duration (15.9+/-4.6 ms vs. 15.6+/-4.0 ms; P=NS), decrease electrogram amplitude (3.8+/-1.5 mV vs. 3.8+/-1.5 mV; P=NS), or increase fragmentation (2.0+/-0.5 vs. 1.9+/-0.4; P=NS). CONCLUSION: Intramyocardial bone marrow cell injection does not increase the incidence of ventricular arrhythmias and does not alter the electrophysiological properties of the injected myocardium. PMID- 17341384 TI - Cell therapy to treat cardiac ischemia: angina-free and arrhythmia-free? PMID- 17341385 TI - Electrophysiologic characteristics of anger-triggered arrhythmias. AB - BACKGROUND: Anger can precipitate ventricular arrhythmias in patients with implantable cardioverter-defibrillators (ICDs). Determining electrophysiologic characteristics of anger-triggered arrhythmias may help elucidate the mechanisms that link emotion and arrhythmia. OBJECTIVES: We sought to compare the morphology and initiation pattern between ventricular arrhythmias that are triggered by anger and those that are not. METHODS: At the time of shock, patients with ICDs recorded levels of defined mood states preceding the shock in a diary. Stored intracardiac electrograms (EGMs) were retrieved and analyzed in relation to corresponding mood states. The EGMs from 56 appropriate shocks in 24 patients (18 male, mean age 66 years, 74% with coronary artery disease) were reviewed and analyzed for morphology, mechanism of initiation (sudden onset vs. premature ventricular contraction [PVC]), pause dependence, and other characteristics. RESULTS: Polymorphic ventricular tachycardia was more common in anger-triggered events, occurring in three (37.5%) of eight anger-triggered events compared with five (10.4%) of 48 of non-anger-triggered events (P <.05). Anger-triggered events were more likely to have PVC initiation, occurring in eight (100%) of eight, compared with 30 (68%) of 44 of non-anger-triggered events (P <.05). More anger triggered events were pause dependent: five (62.5%) of eight versus seven (15%) of 37 non-anger-related events (P <.01). No difference in response to initial therapy was observed in anger-triggered arrhythmias. CONCLUSION: Ventricular arrhythmias occurring in the setting of anger are more likely pause dependent and polymorphic. This suggests that in predisposed populations anger may create an arrhythmogenic substrate susceptible to more disorganized rhythms, a possible mechanism linking emotion and sudden death. PMID- 17341386 TI - Anger and arrhythmias. PMID- 17341387 TI - Heart rate-corrected QT interval in men increases during winter months. AB - BACKGROUND: Sudden cardiac death increases during winter months in both men and women. The heart rate-corrected QT (QTc) interval exhibits circadian variation. However, little is known about QTc interval variation with month of year. OBJECTIVE: We sought to determine whether the QTc interval varies with month of year. METHODS: We retrospectively analyzed a database of 24,370 electrocardiograms (ECGs) to determine seasonal variation in QTc intervals. The analysis data set included 7,976 baseline ECGs, one each for 3,700 men and 4,276 women. ECGs selected for analysis were normal, recorded in regions north of the equator, and taken on subjects >or=18 years old. The QT correction for heart rate (HR) was performed using QTc = QT*(HR/60)(0.4). The monthly mean QTc intervals were compared, for men and women separately, using a one-way analysis of variance with the Bonferroni correction for multiple comparisons. RESULTS: Subject ages ranged from 18 to 95 years. The monthly mean QTc intervals were consistently greater for women than for men by 5.2 +/- 2.3 ms. After correction for multiple comparisons, the difference between the greatest and least monthly mean QTc interval was 6.1 +/- 1.5 ms (P <.01) for men and 3.5 ms (nonsignificant) for women. The maximum monthly mean QTc interval of 413 +/- 18 ms (n = 560; P <.05) occurred in October for men and of 417 +/- 16 ms (n = 350) in March for women, but it was not significant. CONCLUSIONS: Significant seasonal variation in QTc interval exists among male subjects >or=18 years of age with normal baseline ECGs, with the QTc interval being longest in October. No significant variation was seen for women. PMID- 17341388 TI - When should QT be measured? Summer solstice or Christmas Eve? PMID- 17341389 TI - Heart rate turbulence parameters correlate with post-premature ventricular contraction changes in muscle sympathetic activity. AB - BACKGROUND: Heart rate turbulence (HRT) has been shown to be vagally mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) after a premature ventricular contraction (PVC) remains unclear. OBJECTIVE: We sought to evaluate the relationship between HRT and the changes in peripheral SNA after PVCs. METHODS: We recorded postganglionic muscle SNA during electrocardiogram monitoring in eight patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during (1) the dominant burst after the PVC (dominant burst area) and (2) the 10 seconds after the dominant burst (postburst SNA). RESULTS: The mean TO was 0.1% +/- 4.6%, and the mean TS was 6.1 +/- 6.6. The dominant burst area negatively correlated with TO (r = -0.50, P = .0002). The postburst SNA showed a significant positive correlation with TO (r = 0.44, P = .001) and a negative correlation with TS (r = 0.42, P = .002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. CONCLUSIONS: Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease. PMID- 17341390 TI - Last piece of the heart rate turbulence puzzle? PMID- 17341392 TI - Teasing out circadian variability in heart rate turbulence: A new approach to detecting biorhythms underlying cardiac function. PMID- 17341391 TI - Demonstration of circadian rhythm in heart rate turbulence using novel application of correlator functions. AB - BACKGROUND: Demonstration of a circadian rhythm in two parameters of heart rate turbulence--turbulence onset (TO) and turbulence slope (TS)--has been difficult. OBJECTIVE: The aim of this study was to devise a new method for detecting circadian rhythm in noisy data and to apply it to selected Holter recordings from two postmyocardial infarction databases: Cardiac Arrhythmia Suppression Trial (CAST, n = 684) and Innovative Stratification of Arrhythmic Risk (ISAR, n = 327). METHODS: For each patient, TS and TO were calculated for each hour with >4 ventricular premature contractions (VPCs). An autocorrelation function Corr(Deltat) = then was calculated and averaged over all patients. Positive Corr(Deltat) indicates that TS at a given hour and Deltat hours later are similar. TO was treated likewise. Simulations and mathematical analysis showed that a circadian rhythm required Corr(Deltat) to have a U-shape consisting of positive values near Deltat = 0 and 23 and negative values for intermediate Deltat. Significant deviation of Corr(Deltat) from the correlator function of pure noise was evaluated as a Chi-square value. RESULTS: Circadian patterns were not apparent in hourly averages of TS and TO plotted against clock time, which had large error bars. However, their correlator functions produced Chi-square values of approximately 10 in CAST (both P <.0001) and approximately 3 in ISAR (both P <.0001), indicating the presence of circadian rhythmicity. CONCLUSION: Correlator functions may be a powerful tool for detecting the presence of circadian rhythms in noisy data, even with recordings limited to 24 hours. PMID- 17341393 TI - Simultaneous transesophageal cardioversion and echocardiography: feasibility and safety. AB - BACKGROUND: Transesophageal echocardiography (TEE) is routinely used to exclude atrial thrombus prior to cardioversion of atrial fibrillation (AF). Because the TEE probe lies adjacent to the atria, cardioversion using an electrode attached to the TEE probe should allow for immediate low-energy transesophageal cardioversion. OBJECTIVE: The purpose of this study was to evaluate a cardioversion electrode sheath that can be affixed to conventional TEE probes for simultaneous thrombus exclusion and cardioversion of AF. METHODS: A thin electrode was integrated into a latex or polyurethane sheath covering a conventional TEE probe. TEE thrombus exclusion and biphasic transesophageal cardioversion using a step-up protocol were performed during deep sedation. Esophagoscopy was performed immediately after cardioversion and after 1 week. RESULTS: TEE was performed in 27 patients. One patient showed left atrial thrombi. Transesophageal cardioversion was successful in 25 of the remaining 26 patients. Mean atrial cardioversion threshold was 63 +/- 48 J. Transesophageal cardioversion restored sinus rhythm in two patients with unsuccessful transthoracic cardioversion. Transesophageal cardioversion in deep sedation was well tolerated. Esophagoscopy revealed slight mucosal damage in three patients at the site of shock application; two of these patients showed signs of gastroesophageal reflux disease. Mucosal damage unrelated to the site of shock delivery was noted in three patients. CONCLUSION: Atrial thrombus exclusion and transesophageal cardioversion of AF via a disposable cardioversion sheath offers the opportunity to perform transesophageal cardioversion and TEE thrombus exclusion during one sedation. It may not be suitable for use in patients with gastroesophageal reflux disease. Transesophageal cardioversion may establish sinus rhythm in selected patients refractory to transthoracic cardioversion. PMID- 17341394 TI - Long-term outcomes of left bundle branch block in high-risk survivors of acute myocardial infarction: the VALIANT experience. AB - BACKGROUND: In survivors of myocardial infarction (MI), new left bundle branch block (LBBB) is associated with adverse outcomes, but its impact is not well described in post-MI patients with left ventricular (LV) systolic dysfunction and/or heart failure (HF). OBJECTIVES: The aim of this study was to determine if new LBBB is an independent predictor of long-term fatal and nonfatal outcomes in high-risk survivors of MI by reviewing data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. METHODS: In VALIANT, 14,703 patients with LV systolic dysfunction and/or HF were randomized to valsartan, captopril, or both a mean of 5 days after MI. Baseline ECG data were available from 14,259 patients. We assessed the predictive value of new LBBB for death and major cardiovascular outcomes after 3 years, adjusting for multiple baseline covariates including LV ejection fraction. RESULTS: At follow-up, patients with new LBBB (608 [4.2%]) compared with patients without new LBBB had more comorbidities and increased adjusted risk of death (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.2-1.6), cardiovascular death (HR 1.4, 95% CI 1.2-1.7), HF (HR 1.3, 95% CI 1.1-1.6), MI (HR 1.5, 95% CI 1.2-1.9), and the composite of death, HF, or MI (HR 1.4, 95% CI 1.2-1.6). CONCLUSION: In post-MI survivors with LV systolic dysfunction and/or HF, new LBBB was an independent predictor of all major adverse cardiovascular outcomes during long-term follow-up. This readily available ECG marker should be considered a major risk factor for long-term cardiovascular complications in high-risk patients after MI. PMID- 17341395 TI - Left bundle branch block is not good for your heart. PMID- 17341396 TI - Differentiation of ventricular and supraventricular tachycardias based on the analysis of the first postpacing interval after sequential anti-tachycardia pacing in implantable cardioverter-defibrillator patients. AB - BACKGROUND: Current discrimination algorithms do not completely avoid inappropriate tachycardia detection. OBJECTIVES: This study analyzes the discrimination capability of the changes of the first postpacing interval (FPPI) after successive bursts of anti-tachycardia pacing (ATP) trains in implantable cardioverter-defibrillator (ICD)-recorded tachycardias. METHODS: We included 50 ICD patients in this prospective study. We hypothesized that the FPPI variability (FPPIV) when comparing bursts with different numbers of beats would be shorter in ventricular tachycardias (VTs) compared with supraventricular tachycardias (SVTs). The ATP (5-10 pulses, 91% of tachycardia cycle length) was programmed for tachycardias >240 ms. RESULTS: Anti-tachycardia pacing was delivered during 37 sinus tachycardias (STs) in an exercise test, 96 induced VTs in an electrophysiological study, and 198 spontaneous episodes (144 VTs and 54 SVTs). The FPPI remained stable after all ATP bursts in VT but changed continuously in SVT; when comparing bursts of 5 and 10 pulses, the FPPIV was shorter in VT (34 +/ 65 vs.138 +/- 69, P<.0001, in all T and 12 +/- 20 vs. 138 +/- 69, P<.0001, in T>or=320 ms) than in SVT. In T>or=320 ms an FPPIVor=3 (23.9%). Thirty-two patients (17%) received a dose of fluconazole >or=6 mg/kg on Day 0. Total costs were lowest for patients started on fluconazole on the culture day with adequate doses ($35,459+/-25,988) compared with all other patients ($52,158+/-53,492) (P=0.0088). After controlling for covariates, each 1 day delay in fluconazole therapy was associated with increased total hospital costs of $6392+/-3000 (P=0.0344), and an adequate fluconazole dose was associated with decreased total hospital costs of $18,744+/-7173 (P=0.0097). A delay or an inadequate dose or fluconazole in patients with candidaemia was associated with increased hospital costs. Improved methods to diagnose patients with candidaemia quickly are needed. PMID- 17341445 TI - Increased striatal gray matter densities in patients with schizophrenia and substance use disorder: a voxel-based morphometry study. AB - We sought to investigate the link between substance abuse and increased striatal gray matter densities (GMD) in schizophrenia, using voxel-based morphometry (VBM). Increased striatal GMD were found in patients with schizophrenia and substance use disorder (n=12), but not schizophrenia only patients (n=11), compared to healthy volunteers (n=15). PMID- 17341446 TI - The critique of sentinel node biopsy as an acceptable way of locally staging breast cancer. PMID- 17341447 TI - Sequence analysis and tissue expression pattern of Sparus aurata chymotrypsinogens and trypsinogen. AB - Two apparently full-length cDNA clones encoding chymotrypsinogens I and II (CHTRI, 1022 bp; CHTRII, 909 bp) and one cDNA clone encoding trypsinogen II (TRPII, 848 bp) were isolated from a cDNA library prepared from gilthead sea bream (Sparus aurata) liver. The deduced amino acid sequences of the isolated cDNAs contain highly conserved residues essential for serine protease catalytic activity and conformational maintenance. The deduced amino acid sequences of CHTRI and CHTRII are 261 aa and 277 aa long, respectively, and share only 61% identity. Sea bream CHTRII appears to be the longest of all known teleostean chymotrypsinogen forms and contains a high number of methionine residues. Compared with CHTRI, CHTRII is more hydrophobic and has a lower isoelectric point. On the other hand, deduced amino acid sequence of TRPII is 241 aa long and has a signal peptide of thirteen amino acid residues and an activation peptide of seven amino acids long. In contrast to CHTRI and CHTRII, TRPII has a low isoelectric point (4.95), which makes it anionic at neutral pH. Northern blot analysis revealed that liver is the major transcription site for all zymogens. As expected, all zymogen transcripts were detected in parts of the digestive tract (stomach, pyloric caeca, anterior and posterior intestine) and pyloric caeca presented the most intense expression. In all tissues and amongst all zymogens, TRPII constitutive expression was the highest. PMID- 17341448 TI - Two growth hormone receptors in Nile tilapia (Oreochromis niloticus): molecular characterization, tissue distribution and expression profiles in the gonad during the reproductive cycle. AB - Growth hormone (GH) has many important physiological roles in the control of growth, metabolism and reproduction, which is mediated by growth hormone receptor (GHR). In this study, two cDNAs encoding GHR were isolated from the liver of Nile tilapia (Oreochromis niloticus). The two cDNAs, one consisting of 1908 bp and the other of 1728 bp, encoding for putative 635- and 575-amino acid GHR (designated ntGHR1 and ntGHR2, respectively), shared 34.4% identity in nucleotide sequence and 29.6% in deduced amino acid sequence. Northern blot analysis indicated a single 6.0-kb transcript of ntGHR1 and a single 4.0-kb transcript of ntGHR2 in the liver. Real-time RT-PCR analysis showed that both ntGHR1 and ntGHR2 mRNAs were presented in all tissues tested and expressed extremely highly in the liver. In most tissues, ntGHR2 expressed significantly higher than ntGHR1. Analysis of the ntGHRs expression profiles in the gonad during reproductive cycle indicated that the mRNA levels of ntGHRs in ovary were significantly higher at sexual matured stage while those in testis were significantly higher at sexual recrudescent stage, suggesting that GH/IGF-I axis might be involved in reproduction under a regulatory mechanism of GHR gene expression. PMID- 17341449 TI - Soft tissue inflammation: presenting feature of Crohn's disease in a cystic fibrosis adolescent. AB - We report Crohn's disease in an adolescent with cystic fibrosis (CF). The patient suffered from recurrent abdominal symptoms, which were attributed to distal intestinal obstruction syndrome (DIOS) until a soft tissue inflammation at the right lumbar region and iliac crest revealed an enterosubcutaneous fistula. The diagnosis of Crohn's disease was confirmed on the basis of radiological, endoscopic and histological findings. PMID- 17341450 TI - Acute and chronic responses of the upper airway to inspiratory loading in healthy awake humans: an MRI study. AB - We assessed upper airway responses to acute and chronic inspiratory loading. In Experiment I, 11 healthy subjects underwent T(2)-weighted magnetic resonance imaging (MRI) of upper airway dilator muscles (genioglossus and geniohyoid) before and up to 10 min after a single bout of pressure threshold inspiratory muscle training (IMT) at 60% maximal inspiratory mouth pressure (MIP). T(2) values for genioglossus and geniohyoid were increased versus control (p<0.001), suggesting that these airway dilator muscles are activated in response to acute IMT. In Experiment II, nine subjects underwent 2D-Flash sequence MRI of the upper airway during quiet breathing and while performing single inspirations against resistive loads (10%, 30% and 50% MIP); this procedure was repeated after 6 weeks of IMT. Lateral narrowing of the upper airway occurred at all loads, whilst anteroposterior narrowing occurred at the level of the laryngopharynx at loads > or =30% MIP. Changes in upper airway morphology and narrowing after IMT were undetectable using MRI. PMID- 17341451 TI - Deforestation and apparent extinctions of endemic forest beetles in Madagascar. AB - Madagascar has lost about half of its forest cover since 1953 with much regional variation, for instance most of the coastal lowland forests have been cleared. We sampled the endemic forest-dwelling Helictopleurini dung beetles across Madagascar during 2002-2006. Our samples include 29 of the 51 previously known species for which locality information is available. The most significant factor explaining apparent extinctions (species not collected by us) is forest loss within the historical range of the focal species, suggesting that deforestation has already caused the extinction, or effective extinction, of a large number of insect species with small geographical ranges, typical for many endemic taxa in Madagascar. Currently, roughly 10% of the original forest cover remains. Species area considerations suggest that this will allow roughly half of the species to persist. Our results are consistent with this prediction. PMID- 17341452 TI - Biomimetic materials research: what can we really learn from nature's structural materials? AB - Nature provides a wide range of materials with different functions and which may serve as a source of bio-inspiration for the materials scientist. The article takes the point of view that a successful translation of these ideas into the technical world requires more than the observation of nature. A thorough analysis of structure-function relations in natural tissues must precede the engineering of new bio-inspired materials. There are, indeed, many opportunities for lessons from the biological world: on growth and functional adaptation, about hierarchical structuring, on damage repair and self-healing. Biomimetic materials research is becoming a rapidly growing and enormously promising field. Serendipitous discovery from the observation of nature will be gradually replaced by a systematic approach involving the study of natural tissues in materials laboratories, the application of engineering principles to the further development of bio-inspired ideas and the generation of specific databases. PMID- 17341453 TI - Stem cell research in China. AB - In the past 5 years, China has increased its efforts in the field of stem cell research and practice. Basic research mainly focuses on bone marrow and embryonic stem cells. Clinical applications of stem cells in the treatment of acute heart failure, acute liver failure and lower limb ischaemia have been reported by many hospitals. China enacted its 'Ethical Guidelines for Human Embryonic Stem Cell Research' in 2003. At present, China has the most liberal and favourable environments for human embryonic stem cell research. PMID- 17341454 TI - A gharial from the Oligocene of Puerto Rico: transoceanic dispersal in the history of a non-marine reptile. AB - The Indian gharial (Gavialis gangeticus) is not found in saltwater, but the geographical distribution of fossil relatives suggests a derivation from ancestors that lived in, or were at least able to withstand, saline conditions. Here, we describe a new Oligocene gharial, Aktiogavialis puertoricensis, from deltaic-coastal deposits of northern Puerto Rico. It is related to a clade of Neogene gharials otherwise restricted to South America. Its geological and geographical settings, along with its phylogenetic relationships, are consistent with two scenarios: (i) that a single trans-Atlantic dispersal event during the Tertiary explains the South American Neogene gharial assemblage and (ii) that stem gharials were coastal animals and their current restriction to freshwater settings is a comparatively recent environmental shift for the group. This discovery highlights the importance of including fossil information in a phylogenetic context when assessing the ecological history of modern organisms. PMID- 17341455 TI - A potential resolution to the lek paradox through indirect genetic effects. AB - Females often prefer males with elaborate traits, even when they receive no direct benefits from their choice. In such situations, mate discrimination presumably has genetic advantages; selective females will produce offspring of higher genetic quality. Over time, persistent female preferences for elaborate secondary-sexual traits in males should erode genetic variance in these traits, eventually eliminating any benefit to the preferences. Yet, strong female preferences persist in many taxa. This puzzle is called the lek paradox and raises two primary questions: do females obtain genetic benefits for offspring by selecting males with elaborate secondary-sexual characteristics and, if so, how is the genetic variation in these male traits maintained? We suggest that indirect genetic effects may help to resolve the lek paradox. Maternal phenotypes, such as habitat selection behaviours and offspring provisioning, often influence the condition and the expression of secondary-sexual traits in sons. These maternal influences are commonly genetic based (i.e. they are indirect genetic effects). Females choosing mates with elaborate traits may receive 'good genes' for daughters in the form of effective maternal characteristics. Recognizing the significance of indirect genetic effects may be important to our understanding of the process and consequences of sexual selection. PMID- 17341456 TI - The 'big spenders' of the steppe: sex-specific maternal allocation and twinning in the saiga antelope. AB - In polygynous mammals, males generally benefit more from extra allocation of maternal resources than females. However, limitations to sex-specific allocation are usually ignored. We propose the 'allocation constraint' hypothesis, whereby maternal resource allocation is more likely to follow life-history predictions in single sex litters than in mixed sex litters, due to limitations in prenatal resource targeting. Consequently, for polygynous species, males in mixed litters are likely to receive suboptimal maternal investment, which may have a negative effect on lifetime reproductive success. We test this hypothesis for the saiga antelope (Saiga tatarica), a highly polygynous species with the highest level of maternal allocation reported among ungulates. At such high reproductive output levels, the limitations on additional investment in males are likely to be particularly acute. However, we demonstrate high levels of sexual dimorphism in both late-stage foetuses and newborn calves, including within the same litter. Male twins with a brother tended to be heavier than those with a sister. This may be due to allocation constraints or differences in maternal quality. We conclude that an explicit focus on potential constraints can enhance the progress in the field of sex-specific maternal allocation in polytocous species. PMID- 17341457 TI - Prey synchronize their vigilant behaviour with other group members. AB - It is generally assumed that an individual of a prey species can benefit from an increase in the number of its group's members by reducing its own investment in vigilance. But what behaviour should group members adopt in relation to both the risk of being preyed upon and the individual investment in vigilance? Most models assume that individuals scan independently of one another. It is generally argued that it is more profitable for each group member owing to the cost that coordination of individual scans in non-overlapping bouts of vigilance would require. We studied the relationships between both individual and collective vigilance and group size in Defassa waterbuck, Kobus ellipsiprymnus defassa, in a population living under a predation risk. Our results confirmed that the proportion of time an individual spent in vigilance decreased with group size. However, the time during which at least one individual in the group scanned the environment (collective vigilance) increased. Analyses showed that individuals neither coordinated their scanning in an asynchronous way nor scanned independently of one another. On the contrary, scanning and non-scanning bouts were synchronized between group members, producing waves of collective vigilance. We claim that these waves are triggered by allelomimetic effects i.e. they are a phenomenon produced by an individual copying its neighbour's behaviour. PMID- 17341458 TI - Experimental evolution of parasite life-history traits in Strongyloides ratti (Nematoda). AB - Evolutionary ecology predicts that parasite life-history traits, including a parasite's survivorship and fecundity within a host, will evolve in response to selection and that their evolution will be constrained by trade-offs between traits. Here, we test these predictions using a nematode parasite of rats, Strongyloides ratti, as a model. We performed a selection experiment by passage of parasite progeny from either early in an infection ('fast' lines) or late in an infection ('slow' lines). We found that parasite fecundity responded to selection but that parasite survivorship did not. We found a trade-off mediated via conspecific density-dependent constraints; namely, that fast lines exhibit higher density-independent fecundity than slow lines, but fast lines suffered greater reduction in fecundity in the presence of density-dependent constraints than slow lines. We also found that slow lines both stimulate a higher level of IgG1, which is a marker for a Th2-type immune response, and show less of a reduction in fecundity in response to IgG1 levels than for fast lines. Our results confirm the general prediction that parasite life-history traits can evolve in response to selection and indicate that such evolutionary responses may have significant implications for the epidemiology of infectious disease. PMID- 17341459 TI - Spreading free-riding snow sports represent a novel serious threat for wildlife. AB - Stress generated by humans on wildlife by continuous development of outdoor recreational activities is of increasing concern for biodiversity conservation. Human disturbance often adds to other negative impact factors affecting the dynamics of vulnerable populations. It is not known to which extent the rapidly spreading free-riding snow sports actually elicit detrimental stress (allostatic overload) upon wildlife, nor what the potential associated fitness and survival costs are. Using a non-invasive technique, we evaluated the physiological stress response induced by free-riding snow sports on a declining bird species of Alpine ecosystems. The results of a field experiment in which radiomonitored black grouse (Tetrao tetrix) were actively flushed from their snow burrows once a day during four consecutive days showed an increase in the concentration of faecal stress hormone (corticosterone) metabolites after disturbance. A large-scale comparative analysis across the southwestern Swiss Alps indicated that birds had higher levels of these metabolites in human-disturbed versus undisturbed habitats. Disturbance by snow sport free-riders appears to elevate stress, which potentially represents a new serious threat for wildlife. The fitness and survival costs of allostatic adjustments have yet to be estimated. PMID- 17341460 TI - Nucleocapsid protein-mediated maturation of dimer initiation complex of full length SL1 stemloop of HIV-1: sequence effects and mechanism of RNA refolding. AB - Specific binding of HIV-1 viral protein NCp7 to a unique 35-base RNA stem-loop SL1 is critical for formation and packaging of the genomic RNA dimer found within HIV-1 virions. NCp7 binding stimulates refolding of SL1 from a metastable kissing dimer (KD) into thermodynamically stable linear dimer (LD). Using UV melting, gel electrophoresis and heteronuclear NMR, we investigated effects of various site specific mutations within the full-length SL1 on temperature- or NCp7-induced refolding in vitro. Refolding involved intramolecular melting of SL1 stems but not dissociation of the intermolecular KD interface. Refolding required only two NCp7 molecules per KD but was limited by the amount of NCp7 present, implying that the protein does not catalytically promote refolding. Efficient refolding depended strictly on the presence and, to a lesser degree, on sequence of a highly conserved G-rich internal loop that normally limits thermal stability of the SL1 stem. Adding two base pairs to the lower stem created a hyperstable SL1 mutant that failed to refold, even when bound by NCp7 at high stoichiometries. NMR analysis of these kinetically trapped mutant RNA-protein complexes indicated that NCp7 initiates refolding by dissociating base pairs in the upper stem of SL1. This study illuminates structural transitions critical for HIV-1 assembly and replication. PMID- 17341461 TI - QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data. AB - Array-based technologies have been used to detect chromosomal copy number changes (aneuploidies) in the human genome. Recent studies identified numerous copy number variants (CNV) and some are common polymorphisms that may contribute to disease susceptibility. We developed, and experimentally validated, a novel computational framework (QuantiSNP) for detecting regions of copy number variation from BeadArray SNP genotyping data using an Objective Bayes Hidden Markov Model (OB-HMM). Objective Bayes measures are used to set certain hyperparameters in the priors using a novel re-sampling framework to calibrate the model to a fixed Type I (false positive) error rate. Other parameters are set via maximum marginal likelihood to prior training data of known structure. QuantiSNP provides probabilistic quantification of state classifications and significantly improves the accuracy of segmental aneuploidy identification and mapping, relative to existing analytical tools (Beadstudio, Illumina), as demonstrated by validation of breakpoint boundaries. QuantiSNP identified both novel and validated CNVs. QuantiSNP was developed using BeadArray SNP data but it can be adapted to other platforms and we believe that the OB-HMM framework has widespread applicability in genomic research. In conclusion, QuantiSNP is a novel algorithm for high-resolution CNV/aneuploidy detection with application to clinical genetics, cancer and disease association studies. PMID- 17341462 TI - Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription. AB - Human immunodeficiency virus type 1 (HIV-1) transcriptional transactivator (Tat) recruits the positive transcription elongation factor b (P-TEFb) to the viral promoter. Consisting of cyclin dependent kinase 9 (Cdk9) and cyclin T1, P-TEFb phosphorylates RNA polymerase II and the negative transcription elongation factor to stimulate the elongation of HIV-1 genes. A major fraction of nuclear P-TEFb is sequestered into a transcriptionally inactive 7SK small nuclear ribonucleoprotein (snRNP) by the coordinated actions of the 7SK small nuclear RNA (snRNA) and hexamethylene bisacetamide (HMBA) induced protein 1 (HEXIM1). In this study, we demonstrate that Tat prevents the formation of and also releases P-TEFb from the 7SK snRNP in vitro and in vivo. This ability of Tat depends on the integrity of its N-terminal activation domain and stems from the high affinity interaction between Tat and cyclin T1, which allows Tat to directly displace HEXIM1 from cyclin T1. Furthermore, we find that in contrast to the Tat-independent activation of the HIV-1 promoter, Tat-dependent HIV-1 transcription is largely insensitive to the inhibition by HEXIM1. Finally, primary blood lymphocytes display a reduced amount of the endogenous 7SK snRNP upon HIV-1 infection. All these data are consistent with the model that Tat not only recruits but also increases the active pool of P-TEFb for efficient HIV-1 transcription. PMID- 17341463 TI - USER friendly DNA engineering and cloning method by uracil excision. AB - Here we report a PCR-based DNA engineering technique for seamless assembly of recombinant molecules from multiple components. We create cloning vector and target molecules flanked with compatible single-stranded (ss) extensions. The vector contains a cassette with two inversely oriented nicking endonuclease sites separated by restriction endonuclease site(s). The spacer sequences between the nicking and restriction sites are tailored to create ss extensions of custom sequence. The vector is then linearized by digestion with nicking and restriction endonucleases. To generate target molecules, a single deoxyuridine (dU) residue is placed 6-10 nt away from the 5'-end of each PCR primer. 5' of dU the primer sequence is compatible either with an ss extension on the vector or with the ss extension of the next-in-line PCR product. After amplification, the dU is excised from the PCR products with the USER enzyme leaving PCR products flanked by 3' ss extensions. When mixed together, the linearized vector and PCR products directionally assemble into a recombinant molecule through complementary ss extensions. By varying the design of the PCR primers, the protocol is easily adapted to perform one or more simultaneous DNA manipulations such as directional cloning, site-specific mutagenesis, sequence insertion or deletion and sequence assembly. PMID- 17341464 TI - Biophysical studies of DNA modified with conformationally constrained nucleotides: comparison of 2'-exo (north) and 3'-exo (south) 'locked' templates. AB - The biophysical properties of oligodeoxyribonucleotides (ODNs) selectively modified with conformationally 'locked' bicyclo[3.1.0]hexane pseudosugars (Maier,M.A., Choi,Y., Gaus,H., Barchi,J.J. Jr, Marquez,V.E., Manoharan,M. (2004) Synthesis and characterization of oligonucleotides containing conformationally constrained bicyclo[3.1.0]hexane pseudosugar analogs Nucleic Acids Res., 32, 3642 3650) have been studied by various techniques. Six separate synthetic ODNs based on the Dickerson Drew dodecamer sequence (CGCGAAT*T*CGCG) were examined where each one (or both) of the thymidines (T*) were substituted with a bicyclic pseudosugar locked in either a North (2'-exo) or South (3'-exo) ring pucker. Circular dichroism spectroscopy, differential scanning calorimetry and (1)H NMR spectroscopy were used to examine the duplex stability and conformational properties of the ODNs. Replacement of one or both thymidines with North-locked sugars (RNA-like) into the dodecamer did not greatly affect duplex formation or melt temperatures but distinct differences in thermodynamic parameters were observed. In contrast, incorporation of South-locked sugar derivatives that were predicted to stabilize this standard B-DNA, had the unexpected effect of causing a conformational equilibrium between different duplex forms at specific strand and salt concentrations. Our data and those of others suggest that although DNA can tolerate modifications with RNA-like (North) nucleotides, a more complicated spectrum of changes emerges with modifications restricted to South (DNA-like) puckers. PMID- 17341465 TI - Crystal structures of DNA:DNA and DNA:RNA duplexes containing 5-(N aminohexyl)carbamoyl-modified uracils reveal the basis for properties as antigene and antisense molecules. AB - Oligonucleotides containing 5-(N-aminohexyl)carbamoyl-modified uracils have promising features for applications as antigene and antisense therapies. Relative to unmodified DNA, oligonucleotides containing 5-(N-aminohexyl)carbamoyl-2' deoxyuridine ((N)U) or 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine ((N)U(m)), respectively exhibit increased binding affinity for DNA and RNA, and enhanced nuclease resistance. To understand the structural implications of (N)U and (N)U(m) substitutions, we have determined the X-ray crystal structures of DNA:DNA duplexes containing either (N)U or (N)U(m) and of DNA:RNA hybrid duplexes containing (N)U(m). The aminohexyl chains are fixed in the major groove through hydrogen bonds between the carbamoyl amino groups and the uracil O4 atoms. The terminal ammonium cations on these chains could interact with the phosphate oxygen anions of the residues in the target strands. These interactions partly account for the increased target binding affinity and nuclease resistance. In contrast to (N)U, (N)U(m) decreases DNA binding affinity. This could be explained by the drastic changes in sugar puckering and in the minor groove widths and hydration structures seen in the (N)U(m) containing DNA:DNA duplex structure. The conformation of (N)U(m), however, is compatible with the preferred conformation in DNA:RNA hybrid duplexes. Furthermore, the ability of (N)U(m) to render the duplexes with altered minor grooves may increase nuclease resistance and elicit RNase H activity. PMID- 17341466 TI - Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation. AB - Simian Virus 40 (SV40) large T antigen (T Ag) is a multifunctional viral oncoprotein that regulates viral and cellular transcriptional activity. However, the mechanisms by which such regulation occurs remain unclear. Here we show that T antigen represses CBP-mediated transcriptional activity. This repression is concomitant with histone H3 deacetylation and is TSA sensitive. Moreover, our results demonstrate that T antigen interacts with HDAC1 in vitro in an Rb independent manner. In addition, the overexpression of HDAC1 cooperates with T antigen to antagonize CBP transactivation function and correlates with chromatin deacetylation of the TK promoter. Finally, decreasing HDAC1 levels with small interfering RNA (siRNA) partially abolishes T antigen-induced repression. These findings highlight the importance of the histone acetylation/deacetylation balance in the cellular transformation mediated by oncoviral proteins. PMID- 17341467 TI - A non-covalent peptide-based carrier for in vivo delivery of DNA mimics. AB - The dramatic acceleration in identification of new nucleic-acid-based therapeutic molecules has provided new perspectives in pharmaceutical research. However, their development is limited by their poor cellular uptake and inefficient trafficking. Here we describe a short amphipathic peptide, Pep-3, that combines a tryptophan/phenylalanine domain with a lysine/arginine-rich hydrophilic motif. Pep-3 forms stable nano-size complexes with peptide-nucleic acid analogues and promotes their efficient delivery into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. We demonstrate that Pep-3-mediated delivery of antisense-cyclin B1-charged-PNA blocks tumour growth in vivo upon intratumoral and intravenous injection. Moreover, we show that PEGylation of Pep-3 significantly improves complex stability in vivo and consequently the efficiency of antisense cyclin B1 administered intravenously. Given the biological characteristics of these vectors, we believe that peptide based delivery technologies hold a true promise for therapeutic applications of DNA mimics. PMID- 17341468 TI - Development of a brief scale of everyday functioning in persons with serious mental illness. AB - We developed and tested the validity of a brief scale to assess everyday functioning in persons with serious mental illness. A sample of 434 adults with schizophrenia or schizoaffective disorder were administered the University of California, San Diego, Performance-Based Skills Assessment (UPSA), which assesses functional skills in 5 areas of life functioning (eg, finances and planning). Through use of factor analysis, we developed the UPSA-Brief, which consists of 2 subscales (communication and financial) from the original UPSA. UPSA-Brief scores were correlated with cognitive functioning, symptoms of psychosis, age, and education. We further tested the sensitivity and specificity of the UPSA-Brief for predicting residential independence using receiver-operating characteristic (ROC) curves. Finally, sensitivity to change was assessed through comparison of 2 interventions for improving UPSA-Brief scores. UPSA-Brief scores were highly correlated with scores on the full version of the UPSA (r = .91), with overall cognitive functioning (r = .57), and with negative symptoms (r = -.32). The discriminant validity of the UPSA-Brief was adequate (ROC area under the curve [AUC] = 0.73; 95% confidence interval [CI]: 0.67-0.78), with greatest dichotomization for the UPSA-Brief at a cutoff score of 60. The UPSA-Brief was significantly better than the Dementia Rating Scale, Positive and Negative Syndromes Scale positive, and Positive and Negative Syndromes Scale negative at predicting residential independence (all P values < .05). Participants receiving a behavioral intervention also improved significantly compared with a support condition (P = .023). The UPSA-Brief has adequate psychometric properties, predicts residential independence, is sensitive to change, and requires only 10 15 minutes to administer. Therefore, the UPSA-Brief may be a useful performance based functional outcome scale. PMID- 17341469 TI - National survey of molecular epidemiology of Staphylococcus aureus colonization in Belgian cystic fibrosis patients. AB - OBJECTIVES: Epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is poorly defined in cystic fibrosis (CF) patients, and S. aureus detection may be hampered by the presence of small colony variants (SCVs). We conducted a multicentre survey to determine the prevalence of S. aureus and MRSA colonization in Belgian CF patients and characterize the phenotype and clonal distribution of their staphylococcal strains. METHODS: S. aureus isolated from CF patients attending nine CF centres were collected. Oxacillin resistance was detected by oxacillin agar screen and mecA PCR. Antibiotic susceptibility was tested by microdilution. MRSA strains were genotyped by PFGE and SCCmec typing and compared with hospital-associated MRSA strains. RESULTS: Laboratories used a diversity of sputum culture procedures, many of which appeared substandard. S. aureus was isolated from 275/627 (44%) CF patients (20% to 72% by centre). The prevalence of SCV colonization was 4%, but SCVs were almost exclusively recovered from patients in two centres performing an SCV search. Phenotypically, 14% of S. aureus isolates were oxacillin-resistant: 79% carried mecA and 19% were SCVs lacking mecA. The mean prevalence of 'true' MRSA colonization was 5% (0% to 17% by centre). By PFGE typing, 67% of CF-associated MRSA were related to five epidemic clones widespread in Belgian hospitals. CONCLUSIONS: This first survey of S. aureus colonization in the Belgian CF population indicated a diversity in local prevalence rates and in proportion of oxacillin-resistant and SCV phenotypes, probably related to variation in bacteriological methods. These findings underscore the need for standard S. aureus detection methods and MRSA control policies in Belgian CF centres. PMID- 17341470 TI - Characterization of In3Mor, a new integron carrying VIM-1 metallo-beta-lactamase and sat1 gene, from Morganella morganii. AB - OBJECTIVES: A carbapenem-resistant Morganella morganii clinical isolate that was phenotypically metallo-beta-lactamase (MBL)-positive was recovered from a Greek patient. The aim of the study was to analyse the structure of the integron containing the MBL gene. METHODS: MICs were determined by the broth microdilution method. PCR assays and nucleotide sequencing were used for identification of bla gene types and mapping of the integron carrying the MBL gene. The location of the MBL allele was investigated by mating experiments and plasmid analysis as well as by Southern blotting of the plasmid extract and gene-specific hybridization with a bla(VIM-1) probe. RESULTS: The strain contained In3Mor, a novel class 1 integron carrying a carbapenemase gene (bla(VIM-1)) associated with a trimethoprim (dfrA1), a streptothricin (sat1) and two aminoglycoside resistance genes (aacA7 and aadA1). Conjugation experiments failed to detect a transferable MBL determinant and plasmid DNA was not visualized. The chromosomal location of bla(VIM-1) was confirmed after hybridization of the chromosomal band with the bla(VIM-1) probe. CONCLUSIONS: Production of a VIM-type MBL in a M. morganii clinical isolate is documented in this study for the first time. Also, the dfrA1 sat1-aadA1 array which is typically described in the variable region of class 2 integrons consistent with that on Tn7 transposons, is originally detected herein in a class 1 integron. PMID- 17341471 TI - Are beta-lactam breakpoints adequate to define non-susceptibility for all Haemophilus influenzae resistance phenotypes from a pharmacodynamic point of view? AB - OBJECTIVES: To investigate the bactericidal activity, against Haemophilus influenzae strains exhibiting different resistance phenotypes, of simulated serum concentrations obtained in humans after administration of 400 mg of cefditoren twice daily, 500 mg of cefuroxime twice daily, 875/125 mg of co-amoxiclav twice daily or 875/125 mg of co-amoxiclav three times daily. METHODS: An in vitro computerized pharmacodynamic simulation was carried out and colony counts determined over 24 h. Four H. influenzae strains were used, one ampicillin susceptible strain (Strain 1) and three ampicillin-resistant strains following CLSI and BSAC breakpoints: one beta-lactamase-positive strain with an MIC of co amoxiclav of 0.5 mg/L (Strain 2), one beta-lactamase-negative ampicillin resistant strain (BLNAR; ampicillin MIC = 16 mg/L) (Strain 3) and one beta lactamase-positive strain with an MIC of co-amoxiclav of 4 mg/L (Strain 4). All strains were susceptible to cefuroxime and co-amoxiclav according to current CLSI breakpoints, but Strains 3 and 4 were resistant according to BSAC breakpoints. All strains exhibited cefditoren MIC or= 6 log(10) reduced with all antibiotics tested at 12 and 24 h. Against Strains 3 and 4, log(10) reductions at 12 and 24 h were significantly higher for cefditoren versus cefuroxime (P < 0.01) (although both exhibited bactericidal activity, i.e. >or= 3 log(10) reduction) and versus the two co-amoxiclav regimens (P < 0.001) (that exhibited negligible initial inocula reductions). CONCLUSIONS: Cefditoren exhibited the highest bactericidal activity maintained over time against ampicillin-resistant H. influenzae, regardless of beta-lactamase production and/or BLNAR phenotype. From the pharmacodynamic perspective, BSAC breakpoints seem more adequate to define or detect BLNAR strains. PMID- 17341472 TI - Less frequent Salmonella serovars as a reservoir of antimicrobial resistance. PMID- 17341473 TI - New immortalized cell lines of patients with small supernumerary marker chromosome: towards the establishment of a cell bank. AB - Sixteen newly established cell lines with small supernumerary marker chromosomes (sSMC) derived from chromosomes 1, 2, 4, 6, 7, 8, 14, 15, 16, 18, 19, 21, and 22 are reported. Two sSMC are neocentric and derived from 15q24.1-qter and 2q35-q36, respectively. Two further cases each present with two sSMC of different chromosomal origin. sSMC were characterized by multicolor fluorescence in situ hybridization for their chromosomal origin and genetic content. Moreover, uniparental disomy of the sister chromosomes of the sSMC was excluded in all nine cases studied for that reason. The 16 cases provide information to establish a refined genotype-phenotype correlation of sSMC and are available for future studies. PMID- 17341474 TI - Twist relates to tubular epithelial-mesenchymal transition and interstitial fibrogenesis in the obstructed kidney. AB - Epithelial-mesenchymal transition (EMT) is a critical step in renal fibrosis. It has been recently reported that a transcription factor, Twist, plays a pivotal role in metastasis of breast tumors by inducing EMT. In this study, we examined whether Twist relates to renal fibrogenesis including EMT of tubular epithelia, evaluating Twist expression level in the unilateral ureteral obstruction (UUO) model. Kidneys of mice subjected to UUO were harvested 1, 3, 7, and 10 days after obstruction. Compared with control kidneys, Twist mRNA-level significantly increased 3 days after UUO (UUO day 3 kidney) and further augmented until 10 days after UUO. Twist expression increased in tubular epithelia of the dilated tubules and the expanded interstitial areas of UUO kidneys, where cell-proliferating appearances were frequently found in a time-dependent manner. Although a part of tubular cells in whole nephron segment were immunopositive for Twist in UUO day 7 kidneys, tubular epithelia downstream of nephron more frequently expressed Twist than upstream of nephron. In UUO day 7 kidneys, some tubular epithelia were confirmed to coexpress Twist and fibroblast-specific protein-1, a marker for EMT, indicating that Twist is involved in tubular EMT under pathological state. Twist was expressed also in a number of alpha-smooth muscle actin-positive myofibroblasts located in the expanded interstitial area of UUO kidneys. From these findings, the present investigation suggests that Twist is associated with tubular EMT, proliferation of myofibroblasts, and subsequent renal fibrosis in obstructed kidneys. PMID- 17341475 TI - Actin-binding proteins coronin-1a and IBA-1 are effective microglial markers for immunohistochemistry. AB - This study identifies the actin-binding protein, coronin-1a, as a novel and effective immunohistochemical marker for microglia in both cell cultures and in formaldehyde-fixed, paraffin-embedded tissue. Antibodies to coronin-1a effectively immunostained microglia in human, monkey, horse, rat, and mouse tissues, even in tissues stored for long periods of time. The identity of coronin 1a-immunoreactive cells as microglia was confirmed using double immunolabeling with cell type-specific markers as well as by morphological features and the distribution of immunoreactive cells. These properties are shared by another actin-binding protein, IBA-1. Unlike IBA-1, coronin-1a immunoreactivity was also detected in lymphocytes and certain other hematopoietic cells. The results indicate that both coronin-1a and IBA-1 are robust markers for microglia that can be used in routinely processed tissue of humans and animals. Because both coronin 1a and IBA-1 are actin-binding proteins that play a role in rearrangement of the membrane cytoskeleton, it suggests that these proteins are critical to dynamic properties of microglia. PMID- 17341476 TI - Expression of liver X receptor alpha in rat fetal tissues at different developmental stages. AB - The liver X receptor (LXR) is a nuclear receptor that acts as a sterol sensor and metabolic regulator of cholesterol and lipid homeostasis. Using a novel LXRalpha specific antibody for immunohistochemistry, we evaluated cellular expression of LXRalpha in fetal rat tissues. In the fetal liver, LXRalpha-positive macrophages appeared at 12 days and their number peaked at 18 days of gestation. In contrast, hepatocytes expressed LXRalpha during the later stage of gestation, suggesting the functional development of the liver during ontogeny. Later, macrophages in spleen and thymus expressed LXRalpha, and some mononuclear cells in the vascular lumen compatible to primitive/fetal macrophages in the fetal circulation were found to express LXRalpha. In vitro, rat monocytes did not express LXRalpha, but monocyte-derived macrophages cultured in the presence of macrophage-colony stimulating factor revealed the distinct expression of LXRalpha in nucleoli. These findings suggest that LXRalpha plays a role in the differentiation of fetal macrophages, particularly hepatic macrophages, in rat development. PMID- 17341477 TI - Expression and localization of plasma transglutaminase factor XIIIA in bone. AB - Transglutaminases (TGs) are protein crosslinking enzymes involved in cell adhesion and signaling and matrix stabilization and maturation, in many cell types and tissues. We previously described that in addition to transglutaminase 2 (TG2), cultured MC3T3-E1 osteoblasts also express the plasma TG Factor XIIIA (FXIIIA). Here we report on the expression and localization of FXIIIA in bone in vivo and provide confirmatory in vitro data. Immunohistochemistry and in situ hybridization demonstrated that FXIIIA is expressed by osteoblasts and osteocytes in long bones formed by endochondral ossification (femur) and flat bones formed primarily by intramembranous ossification (calvaria and mandible). FXIIIA immunoreactivity was localized to osteoblasts, osteocytes, and the osteoid. RT PCR analysis revealed FXIIIA expression by both primary osteoblasts and by the MC3T3-E1 osteoblast cell line. Western blot analysis of bone and MC3T3-E1 culture extracts demonstrated that FXIIIA is produced mainly as a small, 37-kDa form. Sequential RT-PCR analysis using overlapping PCR primers spanning the full FXIIIA gene showed that the entire FXIIIA gene is expressed, thus indicating that the 37 kDa FXIIIA is not a splice variant but a product of posttranslational proteolytic processing. Forskolin inhibition of osteoblast differentiation revealed that FXIIIA processing is regulated by the protein kinase A pathway. PMID- 17341478 TI - Confocal microscopy-based linescan methodologies for intra-Golgi localization of proteins. AB - Localization of resident Golgi proteins to earlier (cis) or later (trans) Golgi compartments has traditionally required quantitative immunocytochemistry and electron microscopy, which are inaccessible to many researchers. For this reason, light microscopy has often been used, initially for localization of Golgi glycotransferases and, more recently, for other Golgi proteins (e.g., Arf1, GBF1, Rab6). Quantitation of light microscopic intra-Golgi localization can be problematic. We describe here a novel quantitative light microscopic methodology using linescans crossing the Golgi ribbon. Our method determines a localization for the unknown protein in a one-dimensional coordinate system in which 0.0 corresponds to localization of a cis marker and 1.0 to localization of a trans marker. We also describe a variant of this methodology in which Golgi morphology is simplified by nocodazole-induced dispersal into ministacks, allowing a fully automated analysis. In our assay, beta1,4-galactosyltransferase-YFP and Golgin97 localize similarly to trans markers, whereas p115, GBF1, and p58-YFP are similarly near other cis markers. The medial Golgi protein alpha1,3-1,6 mannosidase II gives an intermediate localization in this assay. These methodologies may prove useful in instances where electron microscopy is technically difficult as well as when rapid analysis of large numbers of samples is required. PMID- 17341479 TI - Humanization of excretory pathway in chimeric mice with humanized liver. AB - The liver of a chimeric urokinase-type plasminogen activator (uPA)(+/+)/severe combined immunodeficient (SCID) mouse line recently established in Japan could be replaced by more than 80% with human hepatocytes. We previously reported that the chimeric mice with humanized liver could be useful as a human model in studies on drug metabolism and pharmacokinetics. In the present study, the humanization of an excretory pathway was investigated in the chimeric mice. Cefmetazole (CMZ) was used as a probe drug. The CMZ excretions in urine and feces were 81.0 and 5.9% of the dose, respectively, in chimeric mice and were 23.7 and 59.4% of the dose, respectively, in control uPA(-/-)/SCID mice. Because CMZ is mainly excreted in urine in humans, the excretory profile of chimeric mice was demonstrated to be similar to that of humans. In the chimeric mice, the hepatic mRNA expression of human drug transporters could be quantified. On the other hand, the hepatic mRNA expression of mouse drug transporters in the chimeric mice was significantly lower than in the control uPA(-/-)/SCID mice. In conclusion, chimeric mice exhibited a humanized profile of drug excretion, suggesting that this chimeric mouse line would be a useful animal model in excretory studies. PMID- 17341480 TI - Inhibition of paraquat-induced autophagy accelerates the apoptotic cell death in neuroblastoma SH-SY5Y cells. AB - Autophagy is a degradative mechanism involved in the recycling and turnover of cytoplasmic constituents from eukaryotic cells. This phenomenon of autophagy has been observed in neurons from patients with Parkinson's disease (PD), suggesting a functional role for autophagy in neuronal cell death. On the other hand, it has been demonstrated that exposure to pesticides can be a risk factor in the incidence of PD. In this sense, paraquat (PQ) (1,1'-dimethyl-4,4'-bipyridinium dichloride), a widely used herbicide that is structurally similar to the known dopaminergic neurotoxicant MPP(+) (1-methyl-4-phenyl-pyridine), has been suggested as a potential etiologic factor for the development of PD. The current study shows, for the first time, that low concentrations of PQ induce several characteristics of autophagy in human neuroblastoma SH-SY5Y cells. In this way, PQ induced the accumulation of autophagic vacuoles (AVs) in the cytoplasm and the recruitment of a LC3-GFP fusion protein to AVs. Furthermore, the cells treated with PQ showed an increase of the long-lived protein degradation which is blocked in the presence of the autophagy inhibitor 3-methyladenine and regulated by the mammalian target of rapamycin (mTOR) signaling. Finally, the cells succumbed to cell death with hallmarks of apoptosis such as phosphatidylserine exposure, caspase activation, and chromatin condensation. While caspase inhibition retarded cell death, autophagy inhibition accelerated the apoptotic cell death induced by PQ. Altogether, these findings show the relationship between autophagy and apoptotic cell death in human neuroblastoma cells treated with PQ. PMID- 17341481 TI - Concentration dependence of the mechanisms of tributyltin-induced apoptosis. AB - Tributyltin chloride (TBT), an endocrine-disrupting chemical, has been used as a heat stabilizer, agricultural pesticide, and component of antifouling paints. In this study, we investigated the concentration dependence of the mechanisms of tributyltin cytotoxicity in PC12 cells. Exposure of PC12 cells to both 500 nM and 2 microM tributyltin increased the number of cells showing nuclear fragmentation, a typical apoptotic feature, and activated caspase-3. The peak Ca(2+) concentration in 2 microM tributyltin-treated cells was higher than that in 500 nM tributyltin-treated cells. The intracellular Ca(2+) increase induced by 2 microM tributyltin was mediated by Ca(2+) release from both inositol 1,4,5 trisphosphate receptor and ryanodine receptor, while the Ca(2+) increase induced by 500 nM tributyltin was mediated through the voltage-dependent calcium channel (VDCC). Next, we investigated whether the mechanisms leading to cell death after Ca(2+) increase were different. Reactive oxygen species (ROS) were involved only in 2 microM tributyltin-induced cell death, while c-jun N-terminal kinase (JNK) mediated only 500 nM tributyltin-induced toxicity. Thus, caspase-dependent apoptosis caused by 2 microM tributyltin was mediated by a large Ca(2+) increase via inositol 1,4,5-trisphosphate receptor and ryanodine receptor, followed by generation of ROS. Apoptosis caused by 500 nM tributyltin was mediated by a moderate Ca(2+) increase through the VDCC, followed by phosphorylation of JNK. These results suggest that apoptosis by TBT is induced via distinct pathways depending on the TBT concentration, and we showed a rare example that upstream mechanisms of apoptosis are distinct depending on strength of toxic insult. PMID- 17341482 TI - Evaluation of effects from repeated inhalation exposure of F344 rats to high concentrations of propylene. AB - Chronic exposure to propylene does not result in any increased incidence of tumors, yet does increase N7-hydroxypropylguanine (N7-HPGua) adducts in tissue DNA. To investigate any potential for genotoxicity (mutagenicity or clastogenicity), male F344 rats were exposed via inhalation to up to 10,000 ppm propylene for 1, 3, or 20 days (6 h/day, 5 days/week). The endpoints examined included gene (Hprt, splenocytes) and chromosomal (bone marrow micronucleus [MN]) mutations, hemoglobin (hydroxypropylvaline, HPVal) adducts in systemic blood, and DNA adducts (N7-HPGua) in several tissues. Similarly exposed female and male F344 rats, implanted with bromodeoxyuridine (BrdU) minipumps, were evaluated for nasal effects (irritation via histopathology and cell proliferation via BrdU). Internal dose measures provided clear evidence for propylene exposure, with HPVal increased for all exposures; N7-HPGua was increased in all tissues from rats exposed for more than 1 day (except lymphocytes). Saturation of propylene conversion to propylene oxide was apparent from the adduct dose-response curves. There were no biologically significant genotoxic effects demonstrated at any exposure level, with no increase in Hprt mutant frequency or in bone marrow MN formation. In addition, no histopathological changes were noted in rodent nasal tissues nor any induction of cell proliferation in nasal tissues. These results demonstrate that repeated exposure of rats to high concentrations of propylene (< or = 10,000 ppm) does not produce evidence of local nasal cavity toxicity or evidence of systemic genotoxicity to hematopoietic tissue, despite the formation of N7-HPGua adducts. In addition, these data indicate that formation of N7-HPGua does not correlate with any measure of genotoxic effect, neither mutagenic nor clastogenic. PMID- 17341483 TI - Comparative genomic and functional analyses reveal a novel cis-acting PTEN regulatory element as a highly conserved functional E-box motif deleted in Cowden syndrome. AB - Germline mutations in PTEN, encoding a phosphatase on 10q23, cause Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). Approximately, 10% of CS-related PTEN mutations occur in the PTEN promoter and 11% of BRRS-related mutations include large deletions, often favoring the gene's 5' end (exon 1, promoter). In order to better understand the mechanism(s) underlying the deregulation of PTEN in these syndromes, it is important that functional cis regulatory elements be identified. We employed a comparative genomic approach combined with molecular genetic techniques to identify a highly conserved sequence upstream of the PTEN promoter, sharing 80% sequence identity among Homo sapiens, Mus musculus and Rattus norvegicus. Within this region, we identified a canonical E-box sequence (CACGTG) located at position -2181 to -2176, approximately 800 bp upstream of the PTEN core promoter and more than 1.1 kb upstream of its minimal promoter region (located at -958 to -821). In vitro assays suggest that this motif is recognized by members of the basic region-helix loop-helix-leucine-zipper (bHLH-LZ) transcription factor family, USF1 and USF2, and reporter assays indicate that this novel E-box is involved in mediating PTEN transcriptional activation. Four of 30 CS/CS-like patients, without previously identified PTEN mutations, were found with germline deletions of the E-box element. Of the four, three had deletions stretching to exon 1, but not 3' of it; importantly, one classic CS patient harbored a germline deletion localizing to this E-box region, further affirming the role of this element in PTEN's regulation and deregulation, and its contribution to the pathogenesis of CS. PMID- 17341484 TI - Counting potentially functional variants in BRCA1, BRCA2 and ATM predicts breast cancer susceptibility. AB - Rare inactivating mutations in BRCA1, BRCA2, ATM, TP53 and CHEK2 confer relative risks for breast cancer between about 2 and more than 10, but more common variants in these genes are generally considered of little or no clinical significance. Under the polygenic model for breast cancer carriers of multiple low-penetrance alleles are at high risk, but few such alleles have been reliably identified. We analysed 1037 potentially functional single nucleotide polymorphisms (SNPs) in candidate cancer genes in 473 women with two primary breast cancers and 2463 controls. Twenty-five of these SNPs were in BRCA1, BRCA2, ATM, TP53 and CHEK2. Among the 1037 SNPs there were a few significant findings, but hardly more than would be expected in this large experiment. There was, however, a significant trend in risk with increasing numbers of variant alleles for the 25 SNPs in BRCA1, BRCA2, ATM, TP53 and CHEK2 (P(trend) = 0.005). For the 21 of these with minor allele frequency <10% this trend was highly significant (P(trend) = 0.00004, odds ratio for 3 or more SNPs = 2.90, 95% CI 1.69-4.97). The individual effects of most of these risk alleles were undetectably small even in this well powered study, but the risk conferred by multiple variants is readily detectable and makes a substantial contribution to susceptibility. A risk score incorporating a suitably weighted sum of all potentially functional variants in these and a few other candidate genes may provide clinically useful identification of women at high genetic risk. PMID- 17341485 TI - Leucine-rich repeat kinase 2 associates with lipid rafts. AB - Leucine-Rich Repeat Kinase 2 (LRRK2) is a causative gene for the autosomal dominant form of Parkinson's disease (PD). The gene encodes the approximately 280 kDa LRRK2 protein composed of domains such as leucine-rich repeats, Ras in complex proteins (Roc) followed by C-terminal of Roc (COR), mitogen-activated protein kinase kinase kinase (MAPKKK) and WD40. However, the normal function of the protein as well as its contribution to the pathogenesis of PD remains largely unknown. Here we describe the localization of LRRK2 in Golgi apparatus, plasma membrane and synaptic vesicles in cultured cells including mouse primary neurons. The membrane association of LRRK2 resists solubilization by ice-cold 1% Triton X 100, indicating its association through lipid rafts. To investigate whether mutations found in PD patients affect the localization of LRRK2, we transfected various LRRK2 mutants into cultured cells and performed fractionation experiments. Unexpectedly, the mutants are collected in both membrane and soluble fractions in a manner similar to wild type (WT). I2020T mutant LRRK2 associates with lipid rafts, similar to the WT. The lipid raft association of LRRK2 mutants as well as WT LRRK2 suggests that alteration of LRRK2 function on lipid rafts contributes to the pathogenesis of PD. PMID- 17341486 TI - RCAN1 (DSCR1) increases neuronal susceptibility to oxidative stress: a potential pathogenic process in neurodegeneration. AB - Oxidative stress (OS) underlies neuronal dysfunction in many neurodegenerative disorders. Regulator of Calcineurin 1 (RCAN1 or DSCR1) is a dose-sensitive gene whose overexpression has been linked to Down syndrome (DS) and Alzheimer's disease (AD) neuropathology and to the response of cells to stress stimuli. Here, we show that RCAN1 mRNA and protein expression are sensitive to OS in primary neurons, and we evaluate the involvement of RCAN1 dosage in neuronal death induced by OS. We find that Rcan1(-/-) neurons display an increased resistance to damage by H(2)O(2), which can be reverted by RCAN1 overexpression or by exogenous inhibitors of calcineurin. Although increased intracellular Ca(2+) concentration is an important factor in OS-mediated cell death, our results show that Ca(2+) loading after exposure to H(2)O(2) was similar in Rcan1(+/+) and Rcan1(-/-) neurons. Our data further suggest that CaN and NFAT signaling protect against OS in both Rcan1(+/+) and Rcan1(-/-) neurons. To explain the observed differential vulnerability, we therefore propose a mechanism downstream of H(2)O(2)-mediated Ca(2+) entry, involving calcineurin-NFAT signaling. These findings highlight the importance of RCAN1 gene dosage in the modulation of cell survival and death pathways and suggest that changes in the amount of RCAN1 could represent an important mechanism for regulating susceptibility to neurodegeneration, especially in DS and AD. PMID- 17341487 TI - Tissue-specific imprinting of the ZAC/PLAGL1 tumour suppressor gene results from variable utilization of monoallelic and biallelic promoters. AB - The tumour suppressor gene ZAC/PLAGL1 is widely expressed in many human tissues during fetal development and throughout life. It encodes a DNA-binding protein which shares with p53 the ability to regulate apoptosis and cell cycle arrest concurrently. Owing to its anti-proliferative properties, down-regulation or loss of ZAC is believed to deregulate cell growth, and loss of expression has been observed in a number of different cancers. In addition, overexpression of ZAC during fetal development is believed to underlie the rare disorder transient neonatal diabetes mellitus (TNDM). Imprinted expression of ZAC has been demonstrated in many human and mouse tissues, although biallelic transcription has been noted in human peripheral blood leucocytes (PBL). We report here the identification of a second ZAC promoter, which is responsible for the observed biallelic expression. The promoter lies within a previously uncharacterized CpG island ~55 kb upstream of the imprinted CpG island. In PBL, the imprinted CpG island (P1) is differentially methylated and produces monoallelic transcripts, as in other tissues. However, biallelic transcripts predominate and are derived from the alternative CpG island (P2), which is unmethylated. Biallelic P2 expression was also found in adult pancreas, and ZAC expression from this promoter was identified at a low level in all adult human tissues tested. These findings show that regulation of ZAC expression is more complex than previously realized. The existence of the apparently independently-regulated P2 promoter has important implications for the study of ZAC dysregulation in cancer and TNDM. PMID- 17341488 TI - Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. AB - Membrane palmitoylated protein 4 (Mpp4) is a member of the membrane-associated guanylate kinase family. We show that Mpp4 localizes specifically to the plasma membrane of photoreceptor synaptic terminals. Plasma membrane Ca(2+) ATPases (PMCAs), the Ca(2+) extrusion pumps, interact with an Mpp4-dependent presynaptic membrane protein complex that includes Veli3 and PSD95. In mice lacking Mpp4, PMCAs were lost from rod photoreceptor presynaptic membranes. Synaptic ribbons were enlarged, a phenomenon known to correlate with higher Ca(2+). SERCA2 (sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase, type 2), which pumps cytosolic Ca(2+) into intracellular Ca(2+) stores and localizes next to the ribbons, was increased. The distribution of IP(3)RII (InsP(3) receptor, type 2), which releases Ca(2+) from the stores, was shifted away from the synaptic terminals. Synaptic transmission to second-order neurons was maintained but was reduced in amplitude. These data suggest that loss of Mpp4 disrupts a Ca(2+) extrusion mechanism at the presynaptic membranes, with ensuing adaptive responses by the photoreceptor to restore Ca(2+) homeostasis. We propose that Mpp4 organizes a presynaptic protein complex that includes PMCAs and has a role in modulating Ca(2+) homeostasis and synaptic transmission in rod photoreceptors. PMID- 17341489 TI - Absence of Btn1p in the yeast model for juvenile Batten disease may cause arginine to become toxic to yeast cells. AB - Lymphoblast cell lines established from individuals with juvenile Batten disease (JNCL) bearing mutations in CLN3 and yeast strains lacking Btn1p (btn1-Delta), the homolog to CLN3, have decreased intracellular levels of arginine and defective lysosomal/vacuolar transport of arginine. It is important to establish the basis for this decrease in arginine levels and whether restoration of arginine levels would be of therapeutic value for Batten disease. Previous studies have suggested that synthesis and degradation of arginine are unaltered in btn1-Delta. Using the yeast model for the Batten disease, we have determined that although btn1-Delta results in decreased intracellular arginine levels, it does not result from altered arginine uptake, arginine efflux or differences in arginine incorporation into peptides. However, expression of BTN1 is dependent on arginine and Gcn4p, the master regulator of amino acid biosynthesis. Moreover, deletion of GCN4 (gcn4-Delta), in combination with btn1-Delta, results in a very specific growth requirement for arginine. In addition, increasing the intracellular levels of arginine through overexpression of Can1p, the plasma membrane basic amino acid permease, results in increased cell volume and a severe growth defect specific to basic amino acid availability for btn1-Delta, but not wild-type cells. Therefore, elevation of intracellular levels of arginine in btn1 Delta cells is detrimental and is suggestive that btn1-Delta and perhaps mutation of CLN3 predispose cells to keep arginine levels lower than normal. PMID- 17341491 TI - Production of lysophosphatidylcholine by cPLA2 in the brain of mice lacking PPT1 is a signal for phagocyte infiltration. AB - In the majority of neurodegenerative storage disorders, neuronal death in the brain is followed by infiltration of phagocytic cells (e.g. activated microglia, astroglia and macrophages) for the efficient removal of cell corpses. However, it is increasingly evident that these phagocytes may also cause death of adjoining viable neurons contributing to rapid progression of neurodegeneration. Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating, neurodegenerative, lysosomal storage disorder caused by inactivating mutations in the palmitoyl protein thioesterase-1 (PPT1) gene. PPT1 catalyzes the cleavage of thioester linkages in S-acylated (palmitoylated) proteins and its deficiency leads to abnormal accumulation of thioesterified polypeptides (ceroid) in lysosomes causing INCL pathogenesis. PPT1-knockout (PPT1-KO) mice mimic the clinical and pathological features of human INCL including rapid neuronal death by apoptosis and phagocyte infiltration. We previously reported that in PPT1-KO mice, the neurons undergo endoplasmic reticulum stress activating unfolded protein response, which mediates caspase-12 activation and apoptosis. However, the molecular mechanism(s) by which the phagocytic cells are recruited in the PPT1-KO mouse brain remains poorly understood. We report here that increased production of lysophosphatidylcholine (LPC), catalyzed by the activation of cytosolic phospholipase A(2) (cPLA(2)) in the PPT1-KO mouse brain, is a 'lipid signal' for phagocyte recruitment. We also report that an age-dependent increase in LPC levels in the PPT1-KO mouse brain positively correlates with elevated expression of the genes characteristically associated with phagocytes. We propose that increased cPLA(2)-catalyzed LPC production in the brain is at least one of the mechanisms that mediate phagocyte infiltration contributing to INCL neuropathology. PMID- 17341490 TI - PGC-1alpha/beta upregulation is associated with improved oxidative phosphorylation in cells harboring nonsense mtDNA mutations. AB - We have studied the functional effects of nonsense mitochondrial DNA (mtDNA) mutations in the COXI and ND5 genes in a colorectal tumor cell line. Surprisingly, these cells had an efficient oxidative phosphorylation (OXPHOS); however, when mitochondria from these cells were transferred to an osteosarcoma nuclear background (osteosarcoma cybrids), the rate of respiration markedly declined suggesting that the phenotypic expression of the mtDNA mutations was prevented by the colorectal tumor nuclear background. We found that there was a significant increase in the steady-state levels of PGC-1alpha and PGC-1beta transcriptional coactivators in these cells and a parallel increase in the steady state levels of several mitochondrial proteins. Accordingly, adenoviral-mediated overexpression of PGC-1alpha and PGC-1beta in the osteosarcoma cybrids stimulated mitochondrial respiration suggesting that an upregulation of PGC-1alpha/beta coactivators can partially rescue an OXPHOS defect. In conclusion, upregulation of PGC-1alpha and PGC-1beta in the colorectal tumor cells can be part of an adaptation mechanism to help overcome the severe consequences of mtDNA mutations on OXPHOS. PMID- 17341492 TI - Health promotion capacity mapping: the Korean situation. AB - Ten years ago the Republic of Korea enacted the National Health Promotion Act, setting the stage for health promotion action in the country. A National Health Promotion Fund was established, financed through tobacco taxes, which is now one of the largest in the world. However, despite abundant financial resources, the infrastructure needed to plan, implement, coordinate and evaluate health promotion efforts is still underdeveloped. Currently, health promotion capacity mapping efforts are emerging in Korea. Two international capacity mapping tools have been used to assess the Korean situation, namely HP-Source and the Health Promotion Capacity Profile, which was developed prior to the sixth Global Conference of Health Promotion, held in August 2005 in Bangkok, Thailand. The article summarizes and discusses the results of the capacity mapping exercise, highlights its challenges and suggest ways to improve the accuracy of health promotion capacity mapping. PMID- 17341493 TI - GAPWM: a genetic algorithm method for optimizing a position weight matrix. AB - MOTIVATION: Position weight matrices (PMWs) are simple models commonly used in motif-finding algorithms to identify short functional elements, such as cis regulatory motifs, on genes. When few experimentally verified motifs are available, estimation of the PWM may be poor. The resultant PWM may not reliably discriminate a true motif from a false one. While experimentally identifying such motifs remains time-consuming and expensive, low-resolution binding data from techniques such as ChIP-on-chip and ChIP-PET have become available. We propose a novel but simple method to improve a poorly estimated PWM using ChIP data. METHODOLOGY: Starting from an existing PWM, a set of ChIP sequences, and a set of background sequences, our method, GAPWM, derives an improved PWM via a genetic algorithm that maximizes the area under the receiver operating characteristic (ROC) curve. GAPWM can easily incorporate prior information such as base conservation. We tested our method on two PMWs (Oct4/Sox2 and p53) using three recently published ChIP data sets (human Oct4, mouse Oct4 and human p53). RESULTS: GAPWM substantially increased the sensitivity/specificity of a poorly estimated PWM and further improved the quality of a good PWM. Furthermore, it still functioned when the starting PWM contained a major error. The ROC performance of GAPWM compared favorably with that of MEME and others. With increasing availability of ChIP data, our method provides an alternative for obtaining high-quality PWMs for genome-wide identification of transcription factor binding sites. AVAILABILITY: The C source code and all data used in this report are available at http://dir.niehs.nih.gov/dirbb/gapwm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 17341494 TI - Comparative annotation of viral genomes with non-conserved gene structure. AB - MOTIVATION: Detecting genes in viral genomes is a complex task. Due to the biological necessity of them being constrained in length, RNA viruses in particular tend to code in overlapping reading frames. Since one amino acid is encoded by a triplet of nucleic acids, up to three genes may be coded for simultaneously in one direction. Conventional hidden Markov model (HMM)-based gene-finding algorithms may typically find it difficult to identify multiple coding regions, since in general their topologies do not allow for the presence of overlapping or nested genes. Comparative methods have therefore been restricted to likelihood ratio tests on potential regions as to being double or single coding, using the fact that the constrictions forced upon multiple-coding nucleotides will result in atypical sequence evolution. Exploiting these same constraints, we present an HMM based gene-finding program, which allows for coding in unidirectional nested and overlapping reading frames, to annotate two homologous aligned viral genomes. Our method does not insist on conserved gene structure between the two sequences, thus making it applicable for the pairwise comparison of more distantly related sequences. RESULTS: We apply our method to 15 pairwise alignments of six different HIV2 genomes. Given sufficient evolutionary distance between the two sequences, we achieve sensitivity of approximately 84-89% and specificity of approximately 97-99.9%. We additionally annotate three pairwise alignments of the more distantly related HIV1 and HIV2, as well as of two different hepatitis viruses, attaining results of approximately 87% sensitivity and approximately 98.5% specificity. We subsequently incorporate prior knowledge by 'knowing' the gene structure of one sequence and annotating the other conditional on it. Boosting accuracy close to perfect we demonstrate that conservation of gene structure on top of nucleotide sequence is a valuable source of information, especially in distantly related genomes. AVAILABILITY: The Java code is available from the authors. PMID- 17341495 TI - Metabolic network properties help assign weights to elementary modes to understand physiological flux distributions. AB - MOTIVATION: Elementary modes (EMs) analysis has been well established. The existing methodologies for assigning weights to EMs cannot be directly applied for large-scale metabolic networks, since the tremendous number of modes would make the computation a time-consuming or even an impossible mission. Therefore, developing more efficient methods to deal with large set of EMs is urgent. RESULT: We develop a method to evaluate the performance of employing a subset of the elementary modes to reconstruct a real flux distribution by using the relative error between the real flux vector and the reconstructed one as an indicator. We have found a power function relationship between the decrease of relative error and the increase of the number of the selecting EMs, and a logarithmic relationship between the increases of the number of non-zero weighted EMs and that of the number of the selecting EMs. Our discoveries show that it is possible to reconstruct a given flux distribution by a selected subset of EMs from a large metabolic network and furthermore, they help us identify the 'governing modes' to represent the cellular metabolism for such a condition. PMID- 17341496 TI - Andante: reducing side-chain rotamer search space during comparative modeling using environment-specific substitution probabilities. AB - MOTIVATION: The accurate placement of side chains in computational protein modeling and design involves the searching of vast numbers of rotamer combinations. RESULTS: We have applied the information contained within structurally aligned homologous families, in the form of conserved chi angle conservation rules, to the problem of the comparative modeling. This allows the accurate borrowing of entire side-chain conformations and/or the restriction to high probability rotamer bins. The application of these rules consistently reduces the number of rotamer combinations that need to be searched to trivial values and also reduces the overall side-chain root mean square deviation (rmsd) of the final model. The approach is complementary to current side-chain placement algorithms that use the decomposition of interacting clusters to increase the speed of the placement process. PMID- 17341497 TI - AMPer: a database and an automated discovery tool for antimicrobial peptides. AB - MOTIVATION: Increasing antibiotics resistance in human pathogens represents a pressing public health issue worldwide for which novel antibiotic therapies based on antimicrobial peptides (AMPs) may offer one possible solution. In the current study, we utilized publicly available data on AMPs to construct hidden Markov models (HMMs) that enable recognition of individual classes of antimicrobials peptides (such as defensins, cathelicidins, cecropins, etc.) with up to 99% accuracy and can be used for discovering novel AMP candidates. RESULTS: HMM models for both mature peptides and propeptides were constructed. A total of 146 models for mature peptides and 40 for propeptides have been developed for individual AMP classes. These were created by clustering and analyzing AMP sequences available in the public sources and by consequent iterative scanning of the Swiss-Prot database for previously unknown gene-coded AMPs. As a result, an additional 229 additional AMPs have been identified from Swiss-Prot, and all but 34 could be associated with known antimicrobial activities according to the literature. The final set of 1045 mature peptides and 253 propeptides have been organized into the open-source AMPer database. AVAILABILITY: The developed HMM based tools and AMP sequences can be accessed through the AMPer resource at http://www.cnbi2.com/cgi-bin/amp.pl PMID- 17341498 TI - De novo peptide sequencing using ion peak intensity and amino acid cleavage intensity ratio. AB - MOTIVATION: Peptide-sequencing methods by mass spectrum use the following two approaches: database searching and de novo sequencing. The database-searching approach is convenient; however, in cases wherein the corresponding sequences are not included in the databases, the exact identification is difficult. On the other hand, in the case of de novo sequencing, no preliminary information is necessary; however, continuous amino acid sequence peaks and the differentiation of these peaks are required. It is, however, very difficult to obtain and differentiate the peaks of all amino acids by using an actual spectrum. We propose a novel de novo sequencing approach using not only mass-to-charge ratio but also ion peak intensity and amino acid cleavage intensity ratio (CIR). RESULTS: Our method compensates for any undetectable amino acid peak intervals by estimating the amino acid set and the probability of peak expression based on amino acid CIR. It provides more accurate identification of sequences than the existing methods, by which it is usually difficult to sequence. PMID- 17341499 TI - Simulating Epstein-Barr virus infection with C-ImmSim. AB - MOTIVATION: Epstein-Barr virus (EBV) infects greater than 90% of humans benignly for life but can be associated with tumors. It is a uniquely human pathogen that is amenable to quantitative analysis; however, there is no applicable animal model. Computer models may provide a virtual environment to perform experiments not possible in human volunteers. RESULTS: We report the application of a relatively simple stochastic cellular automaton (C-ImmSim) to the modeling of EBV infection. Infected B-cell dynamics in the acute and chronic phases of infection correspond well to clinical data including the establishment of a long term persistent infection (up to 10 years) that is absolutely dependent on access of latently infected B cells to the peripheral pool where they are not subject to immunosurveillance. In the absence of this compartment the infection is cleared. AVAILABILITY: The latest version 6 of C-ImmSim is available under the GNU General Public License and is downloadable from www.iac.cnr.it/~filippo/cimmsim.html PMID- 17341500 TI - Haemolytic uraemic syndrome complicated with norovirus-associated gastroenteritis. PMID- 17341502 TI - ICDs for secondary prevention of sudden death in the older-elderly. PMID- 17341501 TI - A novel echocardiographic predictor of in-hospital mortality and mid-term haemodynamic improvement after pulmonary endarterectomy for chronic thrombo embolic pulmonary hypertension. AB - AIMS: To study whether pre-operative assessment, using echocardiography, of the timing of a particular feature in the pulmonary flow (pulmonary flow systolic notch) may predict in-hospital mortality and mid-term haemodynamic improvement after pulmonary endarterectomy (PEA) for chronic thrombo-embolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: Fifty-eight of 61 consecutive CTEPH patients (aged 53 +/- 14 years; 36 women) who underwent PEA between June 2002 and June 2005 were studied. Clinical, haemodynamic, and echocardiographic variables were assessed pre-operatively and at 3 months post-PEA. Timing of the notch was expressed as notch ratio (NR). Pre-operatively, seven patients had no notch, 33 had NR < 1.0, and 18 had NR > 1.0. NR was associated with in-hospital mortality (P < 0.01). Moreover, multivariable analysis revealed that among pre-operative variables, NR was an independent predictor of residual-increased pulmonary artery systolic pressure (>40 mmHg) at 3 months post-PEA (P = 0.01). Receiver operator characteristic analysis established NR = 1.0 as optimal cutoff to distinguish patients at risk of such unfavourable outcomes, with NR > 1.0 conferring higher risk. CONCLUSION: NR is related with in-hospital mortality and residual pulmonary hypertension after PEA. NR > 1.0 is associated with a higher risk of such unfavourable outcomes. NR may be considered a determinant of eligibility for PEA. PMID- 17341503 TI - Complete isolation of the pulmonary veins and posterior left atrium in chronic atrial fibrillation. Long-term clinical outcome. AB - AIMS: To evaluate the contribution of the posterior left atrium (LA) to chronic atrial fibrillation (AF). METHODS AND RESULTS: Twenty-seven patients with chronic AF were studied. After pulmonary vein (PV) isolation, the posterior-LA was isolated by ablation joining the right- and left-PVs using an irrigated-tip catheter. Isolation was demonstrated by absent/dissociated posterior-LA activity and the inability to pace the region. Ablation impact was determined by the effect on cycle length (CL) and AF termination. Posterior-LA isolation was achieved using 35 +/- 12 min of radiofrequency with total fluoroscopic and procedural durations of 64 +/- 16 and 199 +/- 46 min, resulting in abolition of electrograms (n = 21) or autonomous activity (n = 6; CL 820 +/- 343 ms). AFCL increased from 156 +/- 28 ms to 162 +/- 27 ms with PV-isolation and to 175 +/- 32 ms by posterior-LA exclusion (P < 0.0001). AF persisted in all after PV-isolation and terminated in 5 (19%) during posterior-LA-isolation. After 10 +/- 6 months, 12 patients developed atrial tachycardia (four) or AF (eight); four underwent repeat posterior-LA-isolation, while the others required additional ablation/antiarrhythmics. After 21 +/- 5 months, 17 (63%) were in sinus rhythm following posterior-LA-isolation. CONCLUSION: This study demonstrates the feasibility of complete posterior-LA exclusion by catheter ablation. This strategy results in maintenance of sinus rhythm in 63% at 2 years follow-up. PMID- 17341504 TI - Two great cardiac veins: demonstration by computed tomography, conventional coronary angiography, and during surgery. PMID- 17341505 TI - Integrated mass spectrometric strategy for characterizing the glycans from glycosphingolipids and glycoproteins: direct identification of sialyl Le(x) in mice. AB - The current interest in applying systems biology approaches to studying an organism's form or function promises to reveal further insights into the role of glycosylation in cells and whole organisms. This has prompted the development of a rapid, sensitive method of profiling the glycan component of both glycosphingolipids and glycoproteins from a single sample. Here we report a new mass spectrometric screening strategy for characterizing glycosphingolipid derived oligosaccharides, which can be integrated into an existing highly sensitive glycoprotein glycomics strategy. Using ceramide glycanase to release the glycans from glycosphingolipids, this method provides a reliable profile of the glycosphingolipid-derived glycans present in a sample and has revealed new glycan structures. Glycoproteins are also efficiently recovered using this method, allowing the subsequent analysis of glycoprotein-derived glycans by mass spectrometry. The high sensitivity of this glycomic screening method allowed us to directly characterize the sialyl Le(x) epitope from mouse brain for the first time, where it was observed on an O-mannose structure. Thus, we present a mass spectrometric method that allows glycomic screening of N- and O-glycans as well as glycosphingolipid-derived glycans from a single tissue. PMID- 17341506 TI - Assessing remission in clinical practice. AB - OBJECTIVE: Remission constitutes the best achievable state in patients with rheumatoid arthritis. We aimed at evaluating sustained remission in a large cohort of patients followed prospectively in clinical practice and to evaluate available instruments to define remission for their stringency in defining this state. PATIENTS AND METHODS: We analysed remission and sustained remission in 621 patients who had two consecutive and complete clinical observations; the average period between the two visits was 92 days (median; quartiles: 82; 105). Remission was evaluated according to modified ACR (mACR), 28 Joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) criteria. Sustained remission was defined as remission at both consecutive visits. Patients were treated with traditional disease- modifying antirheumatic drugs, mainly methotrexate, and partly with biological agents (approximately 11%). RESULTS: Remissions at any one of the two visits were seen in 33.5% of patients by SDAI or CDAI, 42.7% by DAS28, and 38.6% by mACR criteria (P < 0.01). Sustained remission was observed in much lower proportions of patients (between 16.7 and 19.6%, dependent on the instrument). Agreement between classifications of remission by kappa-statistics was very good for SDAI vs CDAI, good for DAS28 vs SDAI or CDAI, and only moderate for mACR vs the three other scores. Residual swollen joints were observed in 15% of patients in DAS28 remission (range 1-9), 6% of patients in mACR remission (range 1-8), but only approximately 5% of patients in CDAI or SDAI remission (range 1-2) (P < 0.01). CONCLUSION: Sustained remission can be observed in 17-20% of patients in clinical practice. CDAI and SDAI remission criteria are more stringent than DAS28 and mACR criteria, since they allow for lesser residual disease activity. Consequently, smaller proportions of patients are classified as in remission by SDAI and CDAI than by DAS28 and mACR criteria. Sustained remission is an achievable goal in clinical practice even with the most stringent of the definitions studied. PMID- 17341507 TI - Risk of progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858T-allele in anti-citrullinated peptide antibody positive patients. AB - OBJECTIVES: Anti-citrullinated peptide antibodies (ACPA) and the C1858T missense single-nucleotide polymorphism (SNP) in the PTPN22 gene are both associated with the development of rheumatoid arthritis (RA). We investigated whether the combination of these two biomarkers yielded better test characteristics to predict progression from undifferentiated arthritis (UA) to RA compared with ACPA alone. METHODS: A total of 394 individuals with UA from a Dutch population-based inception cohort were included in this study. At baseline, ACPA were measured and the PTPN22 C1858T and HLA-DRB1 genotypes determined. Progression to RA was monitored at 1 yr after entry into the cohort. RESULTS: A priori, UA patients had a 35% (95% CI 30-40%) risk of developing RA, which increased to 66% (95% CI 57 75%) in patients who were ACPA-positive. There was an additional, although non significant (P = 0.34), increase in RA risk to 76% (95% CI 57-90%) when patients were positive for both ACPA and the PTPN22 1858T-allele. The area under the receiver operator characteristic curve increased from 0.68 for ACPA-status alone to 0.70 for the combination of ACPA-status and the PTPN22 C1858T polymorphism. In logistic regression analysis, ACPA predicted RA-development independent of PTPN22, while the PTPN22 polymorphism had no independent effect. In HLA-DRB1 shared epitope positive, ACPA-positive UA patients, ACPA-levels were significantly increased in PTPN22 1858T allele carriers compared with non-1858T carriers. CONCLUSIONS: In this Dutch cohort of UA-patients, the PTPN22 1858T allele does not markedly improve individual decision-making to predict RA development over ACPA alone, but it is associated with higher ACPA-levels. PMID- 17341508 TI - Socio-demographic patterning of referral, uptake and attendance in Physical Activity Referral Schemes. AB - BACKGROUND: Inadequate monitoring and participant profiling have so far prevented a detailed examination of who Physical Activity Referral Schemes (PARS) are accessible to and appropriate for. As a result, the nature of the role for PARS within public health is unknown. METHODS: Participants were all those referred to a countywide PARS during a three-year period (n = 3568). Participant age, gender and the deprivation level and rurality of their area of residence were compared with the average for the county population. Characteristics associated with referral uptake (attending > or =1 exercise session) and completion (> or =80% attendance), were identified using logistic regression. RESULTS: Compared with the county average, participants were older, more predominantly female (61.1 vs 51.4%) and lived in more deprived areas (p < 0.001). Referral uptake (n = 2864) was most likely in those aged 60-69 years, and least likely for residents of rural villages and the most deprived areas (all p < 0.001). For participants who took up referral, completion was most likely in men and the over-seventies (p < 0.001). CONCLUSIONS: The PARS format may be inappropriate for younger adults or people living in relative deprivation and rural areas. They appear most appropriate for adults of middle-to-old age who are more likely to require supervision, and should be targeted accordingly. PMID- 17341509 TI - Short-term effects of thrust versus nonthrust mobilization/manipulation directed at the thoracic spine in patients with neck pain: a randomized clinical trial. AB - BACKGROUND AND PURPOSE: Evidence supports the use of manual physical therapy interventions directed at the thoracic spine in patients with neck pain. The purpose of this study was to compare the effectiveness of thoracic spine thrust mobilization/manipulation with that of nonthrust mobilization/manipulation in patients with a primary complaint of mechanical neck pain. The authors also sought to compare the frequencies, durations, and types of side effects between the groups. SUBJECTS: The subjects in this study were 60 patients who were 18 to 60 years of age and had a primary complaint of neck pain. METHODS: For all subjects, a standardized history and a physical examination were obtained. Self report outcome measures included the Neck Disability Index (NDI), a pain diagram, the Numeric Pain Rating Scale (NPRS), and the Fear-Avoidance Beliefs Questionnaire. After the baseline evaluation, the subjects were randomly assigned to receive either thoracic spine thrust or nonthrust mobilization/manipulation. The subjects were reexamined 2 to 4 days after the initial examination, and they again completed the NDI and the NPRS, as well as the Global Rating of Change (GROC) Scale. The primary aim was examined with a 2-way repeated-measures analysis of variance (ANOVA), with intervention group (thrust versus nonthrust mobilization/manipulation) as the between-subjects variable and time (baseline and 48 hours) as the within-subject variable. Separate ANOVAs were performed for each dependent variable: disability (NDI) and pain (NPRS). For each ANOVA, the hypothesis of interest was the 2-way group x time interaction. RESULTS: Sixty patients with a mean age of 43.3 years (SD=12.7) (55% female) satisfied the eligibility criteria and agreed to participate in the study. Subjects who received thrust mobilization/manipulation experienced greater reductions in disability, with a between-group difference of 10% (95% confidence interval [CI]=5.3-14.7), and in pain, with a between-group difference of 2.0 (95% CI=1.4 2.7). Subjects in the thrust mobilization/manipulation group exhibited significantly higher scores on the GROC Scale at the time of follow-up. No differences in the frequencies, durations, and types of side effects existed between the groups. DISCUSSION AND CONCLUSION: The results suggest that thoracic spine thrust mobilization/manipulation results in significantly greater short term reductions in pain and disability than does thoracic nonthrust mobilization/manipulation in people with neck pain. PMID- 17341510 TI - Pelvic-floor muscle function in women with pelvic organ prolapse. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine whether pelvic organ prolapse severity, pelvic symptoms, quality of life, and sexual function differ based on pelvic-floor muscle function in women planning to have prolapse surgery. SUBJECTS AND METHODS: Three hundred seventeen women without urinary stress incontinence who were enrolled in a multicenter surgical trial were examined to determine pelvic-floor muscle function (by Brink scale score). The subjects were 61.6+/-10.2 (X+/-SD) years of age. Thirteen percent of the subjects had stage II (to the hymen) pelvic organ prolapse, 68% had stage III (beyond the hymen) prolapse, and 19% had stage IV (complete vaginal eversion) prolapse. Subjects with lowest (3-6) and highest (10-12) Brink scale scores were compared on prolapse severity, pelvic symptoms and bother, quality of life, and sexual function. RESULTS: Subjects with the highest Brink scores (n=75) had less advanced prolapse, smaller genital hiatus measurements, and less urinary symptom burden compared with those with the lowest Brink scores (n=56). The results indicated that pelvic-floor muscle function was not associated with condition specific quality of life or sexual function. DISCUSSION AND CONCLUSION: Although modestly clinically significant, better pelvic-floor muscle function was associated with less severe prolapse and urinary symptoms. PMID- 17341511 TI - Effectiveness of two forms of feedback on training of a joint mobilization skill by using a joint translation simulator. AB - BACKGROUND AND PURPOSE: Joint mobilization is a complicated task to learn and to teach and is characterized by great intersubject variability. This study's purpose was to investigate whether quantitatively augmented feedback could enhance the learning of joint mobilization and, more specifically, to compare the effects of training with concurrent or terminal feedback by using a joint translation simulator (JTS). SUBJECTS: Thirty-six undergraduate physical therapist students were randomly assigned to control (no feedback), concurrent feedback, and terminal feedback groups. METHODS: The JTS was designed to simulate tissue resistance based on load-displacement relationships of glenohumeral joint specimens. Subjects applied specific mobilization grades of force on the JTS while quantitative feedback was given to the feedback groups either during a trial (ie, concurrent feedback) or after a trial (ie, terminal feedback). The skill acquisition phase lasted a total of 40 minutes, and a total of 75 repetitions were performed for each grade of each joint model. Pretest and no feedback retention tests were conducted. RESULTS: During acquisition and retention, both feedback groups performed more accurately than did the control group. No obviously superior performance was shown by the terminal feedback group compared with concurrent feedback group during retention testing. DISCUSSION AND CONCLUSION: Subjects who trained with augmented feedback had less variability, and thus more consistency, than the control group subjects who received no feedback. Augmented feedback provides the student with a reference force and the status of his or her performance. The effectiveness of the JTS feedback compared with no feedback was clearly demonstrated. Skill acquisition in mobilization can be enhanced by either concurrent or terminal feedback. PMID- 17341512 TI - Effect of neck exercise on sitting posture in patients with chronic neck pain. AB - BACKGROUND AND PURPOSE: Poor sitting posture has been implicated in the development and perpetuation of neck pain symptoms. This study had 2 purposes: (1) to compare change in cervical and thoracic posture during a distracting task between subjects with chronic neck pain and control subjects and (2) to compare the effects of 2 different neck exercise regimens on the ability of people with neck pain to maintain an upright cervical and thoracic posture during this task. SUBJECTS: Fifty-eight subjects with chronic, nonsevere neck pain and 10 control subjects participated in the study. METHOD: Change in cervical and thoracic posture from an upright posture was measured every 2 minutes during a 10-minute computer task. Following baseline measurements, the subjects with neck pain were randomized into one of two 6-week exercise intervention groups: a group that received training of the craniocervical flexor muscles or a group that received endurance-strength training of the cervical flexor muscles. The primary outcomes following intervention were changes in the angle of cervical and thoracic posture during the computer task. RESULTS: Subjects with neck pain demonstrated a change in cervical angle across the duration of the task (mean=4.4 degrees ; 95% confidence interval [CI]=3.3-5.4), consistent with a more forward head posture. No significant difference was observed for the change in cervical angle across the duration of the task for the control group subjects (mean=2.2 degrees ; 95% CI=1.0-3.4). Following intervention, the craniocervical flexor training group demonstrated a significant reduction in the change of cervical angle across the duration of the computer task. DISCUSSION AND CONCLUSION: This study showed that people with chronic neck pain demonstrate a reduced ability to maintain an upright posture when distracted. Following intervention with an exercise program targeted at training the craniocervical flexor muscles, subjects with neck pain demonstrated an improved ability to maintain a neutral cervical posture during prolonged sitting. PMID- 17341513 TI - No changes in neocortical cell volumes or glial cell numbers in chronic alcoholic subjects compared to control subjects. AB - AIMS: To study if the total glial cell population in the neocortex is intact in subjects with a history of severe alcohol abuse compared to control subjects. Further, to investigate whether the cortical nerve cell nuclei and nerve cell perikarya volumes are the same in chronic alcoholic subjects as in the control subjects. METHODS: Using the stereological method, the optical rotator in a vertical design, the perikaryon cell volume and nuclei cell volume in the neocortex and its four subdivisions were studied in 11 alcoholics and 10 control subjects. Using the Cavalieri estimator of volumes and the optical disector for cell counting, we estimated the total number of glial cells in the neocortex and compared previous stereological results for chronic alcoholic subjects. RESULTS: We found the mean neuronal cell volumes to be unaffected by severe alcohol abuse (p = 0.84) and a normal total number of glial cells (p = 0.39) in chronic alcoholic subjects compared to control subjects. CONCLUSION: Only glial cells and dendritic/synaptic changes have so far been reported in stereological studies of the brains of alcoholic subjects. We thus have increasing evidence that it may be possible for some individuals to return to their previous cognitive abilities after cessation of alcohol which may give hope and encouragement for chronic alcoholic subjects to stop the abuse. PMID- 17341514 TI - Clinical approach to intestinal maturation in neonates prenatally exposed to alcohol. AB - AIM: The need for a non-invasive diagnosis of the effects of ethanol in utero on the development of the intestine in humans led us to look for a serum marker of the structural integrity of the intestine. We propose apolipoprotein A-IV (apoA IV) as a possible candidate. In humans this protein is synthesized only by intestinal mucosa, it is expressed in the enterocyte of the foetus from 20 weeks of gestation, and it is released to the blood stream after synthesis. METHODS: We measured the levels of apoA-IV in the umbilical cord serum of neonates whose mothers had consumed alcohol during pregnancy and neonates born to women who had not (controls). The gestational age at delivery of the cases studied ranged from 36 to 42 weeks. ELISA and Western blot analysis were used. RESULTS: There was no difference in the mean body weight of neonates from either group. Nevertheless, exposure to ethanol in utero significantly reduced (by about 30%) the apoA-IV levels in serum at birth, regardless of body weight. CONCLUSION: Our findings suggest that circulating apoA-IV levels could be used as a clinical marker of the prenatal effects of ethanol on the structural integrity of the intestine. Neonatal diagnosis of these intestinal effects could improve post-natal outcome. PMID- 17341515 TI - Effect of using different modes to administer the AUDIT-C on identification of hazardous drinking and acquiescence to trial participation among injured patients. AB - AIMS: We compared the effect of three different modes of questionnaire administration on screening for hazardous drinking and acquiescence to trial participation. METHODS: A quasi-randomized controlled trial among injured patients seen in acute care clinics compared self-administered paper-and-pencil, self-administered electronic, and orally-administered interview questionnaires. Outcomes included positive AUDIT-C screens for hazardous drinking, willingness to participate in a (hypothetical) lifestyle intervention trial, and recruitment success. Differences were analyzed with nonlinear mixed models, controlling for age, sex, and facility. Structured interviews with staff explored levers and barriers to screening. RESULTS: Of the 370 participants, 22.7% scored > or =4 and 7.8% > or =6 on the AUDIT-C. Electronic questionnaires were more likely than paper questionnaires to identify an AUDIT-C > or =6 (OR = 1.96; 95% CI 1.10 3.48), but not > or =4 (OR = 0.83; 95% CI 0.43-1.62). Oral questionnaires were as likely as paper questionnaires to identify an AUDIT-C > or =4 (OR = 1.00; 95% CI 0.40-2.51) or > or =6 (OR = 1.94; 95% CI 0.83-4.50). Electronic and oral questionnaires were more likely to elicit acquiescence to trial participation (OR = 1.59; 95% CI 1.23-2.07, and OR = 1.66; 95% CI 1.22-2.26, respectively). Oral questionnaires created problems with confidentiality, privacy, and disruption of patient flow, and reduced recruitment success (OR = 0.51; 95% CI 0.42-0.62). CONCLUSIONS: Among acutely injured patients in clinics who consented to screening, nearly one-fourth reported hazardous drinking. Compared to paper questionnaires, electronic screening produced less social desirability bias and greater acquiescence to trial participation. Oral questionnaires produced greater acquiescence, but barriers to use adversely affected recruitment. Electronic questionnaires may be preferable for screening for hazardous drinking and recruitment into intervention trials in acute care clinics. PMID- 17341516 TI - Effects of chronic ethanol drinking on the blood brain barrier and ensuing neuronal toxicity in alcohol-preferring rats subjected to intraperitoneal LPS injection. AB - AIMS: Although alcohol drinking impairs the blood-brain barrier (BBB), the underlying mechanism is not fully understood. Thus, the effects of chronic ethanol drinking on the BBB were studied in vivo. METHODS: Alcohol-preferring rats were given for 70 days free choice water and 15% ethanol. Then, they received LPS by i.p. injection. Efflux of [(14)C]sucrose or [(14)C]dextran was measured by their microinjection into the brain. Endothelial cells and neurons were isolated from the brain and analysed for mitogen-activated protein kinase (MAPK) and the tight-junction (TJ) protein phosphorylation, NFkappaB activation, mRNA levels of TJ proteins, inducible nitric oxide synthase, tumour necrosis factor alpha, interleukin-1 beta (IL-1beta), IL-10, CASPASE-8, and DNA damage. RESULTS: LPS transiently increased [(14)C]sucrose efflux in water drinking, while it caused a lasting increase in [(14)C]sucrose and [(14)C]dextran efflux in ethanol-drinking rats. The time-course of changes in the TJ correlated with (i) an increase in extracellular signal-regulated kinase (ERK), p38(mapk) Jun-N terminal Kinase (JNK), and TJ protein phosphorylation, (ii) RelA-p50 and p50-p50 activation, and (iii) a decrease in the TJ proteins' mRNA levels in endothelial cells and neurons. Apoptotic cells were detected in water drinking and LPS (WC LPS) neurons at 24 h after LPS exposure. Neurons from Et-LPS rats did not exhibit apoptosis. CONCLUSIONS: LPS injection in WC-LPS rats transiently disrupted the BBB. Lack of JNK activation and CASPASE-8 may be responsible for lack of apoptosis in endothelial cells and vice versa in neurons. Chronic alcohol drinking in ethanol drinking and LPS (Et-LPS) rats augmented and dysregulated the LPS-induced BBB abnormalities but suppressed apoptosis in neurons. PMID- 17341517 TI - How do public health policies tackle alcohol-related harm: a review of 12 developed countries. AB - AIMS: To identify how current public health policies of 12 developed countries assess alcohol-related problems, the goals and targets that are set and the strategic directives proposed. METHODS: Policy documents on alcohol and on general public heath were obtained through repeated searches of government websites. Documents were reviewed by two independent observers. RESULTS: All the countries studied state that alcohol causes substantial harm to individual health and family well-being, increases crime and social disruption, and results in economic loss through lost productivity. All are concerned about consumption of alcohol by young adults and by heavy and problem drinkers. Few aim to reduce total consumption. Only five of the countries set specific targets for changes in drinking behaviour. Countries vary in their commitment to intervene, particularly on taxation, drink-driving, the drinking environment and for high-risk groups. Australia and New Zealand stand out as having coordinated intervention programmes in most areas. CONCLUSIONS: Policies differ markedly in their organization, the goals and targets that are set, the strategic approaches proposed and areas identified for intervention. Most countries could improve their policies by following the recommendations in the World Heath Organization's European Alcohol Action Plan. PMID- 17341518 TI - Weekday distribution of head traumas in patients admitted to the emergency department of a city hospital: effects of age, gender and drinking pattern. AB - AIMS: To define the alcohol-related risk for head traumas and to compare the weekly and monthly variations in alcohol consumption, and the occurrence of head traumas in a population with heavy episodic drinking as the prevailing drinking pattern. METHODS: All consecutive admissions due to head trauma into a Finnish city hospital during 1 year (1999) were recorded. 832 consecutive patients with data on alcohol consumption were covered. We compared the number of final diagnoses of head traumas per day and month to the anticipated frequency in the absence of any weekly or monthly variation. Official statistics on alcohol consumption in Finland are presented as reference. RESULTS: Alcohol-related head traumas were most common in young adults and people of working age. The occurrence of head traumas in sober subjects showed no temporal variations. By contrast, alcohol-related cases peaked on weekends and in the most popular vacation month (July). The alcohol-related risk from Friday to Sunday was 27.3% in women and 20.3% in men. The additional risk related to alcohol consumption in July was 16.1% in women and 5.3% in men. CONCLUSIONS: We found an excess of head traumas during weekends and the primary vacation month, and this excess was associated with heavy episodic drinking. Active measures are needed to prevent head traumas caused by this type of behaviour. PMID- 17341519 TI - Alcohol and prisons: report of a workshop held by WHO HIPP at the Eurocare Bridging the Gap Conference, Helsinki, November 2006. PMID- 17341520 TI - Comment: low-dose orlistat effects on body weight of mildly to moderately overweight individuals: a 16 week, double-blind, placebo-controlled trial. PMID- 17341522 TI - Cost-justification of a clinical pharmacist-managed anticoagulation clinic. AB - A cost-benefit evaluation of a clinical pharmacist-managed anticoagulation clinic (AC) was performed. Outpatient and hospital records were examined for 26 patients in the treatment group with an AC clinic and 26 patients in the control group. Therapeutic prothrombin times were maintained within the treatment group to a significantly greater extent than within the control group (p<0.001). The AC was successful in preventing hospitalizations resulting from hemorrhage or thromboembolic admissions (p<0.05, p<0.005, respectively). Patients were hospitalized 3.22 days and .048 days per patient-treatment-year in the control and treatment groups, respectively. The net savings in reduced hospitalization costs per year in the treatment group was $211,776. The benefit:cost ratio (B:C) was 6.55, suggesting the program is socially valuable. This clinical pharmacist managed AC was effective in maintaining therapeutic prothrombin times, and reducing the incidence of hospitalizations resulting from anticoagulation complications, and can be cost-justified based on a cost-benefit analysis. PMID- 17341523 TI - Advances in anticoagulation management: the role of pharmacy. PMID- 17341524 TI - New serum creatinine assay standardization: implications for drug dosing. AB - OBJECTIVE: To describe the development of new serum creatinine assay standards and discuss their implications for various drug dosing scenarios. DATA SOURCES: A MEDLINE search (1990-August 2006) was performed to identify literature on newly developed serum creatinine assay standards and the impact those standards will have on drug dosing. STUDY SELECTION AND DATA EXTRACTION: Data on the development of new creatinine assay procedures and the effect that these new values will have on drug dosing were extracted from identified references. DATA SYNTHESIS: The National Kidney Foundation's current practice guidelines recommend standardization of serum creatinine assay calibration to increase assay accuracy. This will result in a lower than the current range of values being considered normal, as well as lower value patient values. These lower creatinine values will result in higher calculated glomerular filtration rates and creatinine clearance (Cl(cr)) estimates, resulting in the difficulty of clinicians applying these values to current manufacturers' recommended drug dose modification tables in patients with declining renal function. Newer creatinine values may be as much as 5-20% lower than older assay values. CONCLUSIONS: Worldwide implementation of new serum creatinine calibration standards will produce more accurate serum creatinine values. These values may be slightly lower than those obtained with older methods. This, in turn, may cause slightly higher Cl(cr) estimates that may no longer match drug manufacturers' data for dosage adjustment in renal insufficiency, given that manufacturers' dosing tables were based on older creatinine values. If this is deemed clinically significant in a specific patient, increasing the creatinine value obtained with new assay techniques by 5 20% may give the clinician a value that more closely approximates that used by the drug manufacturer in developing these tables. This revised value can then be used for dosage adjustments. PMID- 17341525 TI - Effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on the frequency of post-cardiothoracic surgery atrial fibrillation. AB - BACKGROUND: A recent meta-analysis demonstrated that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) reduce the incidence of new-onset atrial fibrillation by nearly 50%. However, the ability of ACE inhibitors or ARBs to prevent post-cardiothoracic surgery (CTS) atrial fibrillation, when used postoperatively, has yet to be evaluated. OBJECTIVE: To evaluate the impact of postoperative ACE inhibitor or ARB use on the incidence of post-CTS atrial fibrillation. METHODS: We performed a retrospective cohort study of propensity score matched patients who underwent CTS at a single institution from January 2004 through December 2005. Patients who received either an ACE inhibitor or an ARB within 24 hours of surgery were propensity score matched for common predictors of post-CTS atrial fibrillation (age >70 y, preoperative digoxin use, postoperative beta-blocker or amiodarone use, beta-blocker intolerance, valve surgery, male sex, and history of diabetes mellitus, smoking, chronic obstructive pulmonary disease, prior cardiothoracic surgery) in a 1:1 ratio with patients who did not receive an ACE inhibitor or an ARB. Multivariate logistic regression was used to generate adjusted odds ratios to minimize the impact of baseline confounders. RESULTS: A total of 1469 patients underwent CTS during the study evaluation period. Postoperatively, 188 received an ACE inhibitor or an ARB and were matched to 188 control patients. Mean +/- SD age of matched patients was 68.1 +/- 11.8 years, 66% were men, 42% underwent valve surgery, and 69% and 35% received postoperative beta-blockade and amiodarone, respectively. Patients who received an ACE inhibitor or an ARB did not experience a significant reduction in post-CTS atrial fibrillation compared with control patients (adjusted OR 0.95; 95% CI 0.57 to 1.56; p = 0.83). CONCLUSIONS: In this evaluation, postoperative ACE inhibitor or ARB use was not associated with a reduction in post-CTS atrial fibrillation. A study of preoperative, longer-term ACE inhibitor and/or ARB therapy is needed to determine the benefits of that strategy. PMID- 17341526 TI - Solifenacin for overactive bladder with incontinence: symptom bother and health related quality of life outcomes. AB - BACKGROUND: Approximately one-third of patients with overactive bladder (OAB) experience incontinence, a bothersome symptom with a clear negative effect on quality of life. OBJECTIVE: To assess OAB patients' perceptions of improvements in symptom bother and quality of life after taking solifenacin under conditions reflecting day-to-day practice. METHODS: VOLT (the VESIcare Open-Label Trial) was a prospective, open-label study in patients with OAB (defined as urgency, urge urinary incontinence, daytime frequency, or nocturia for > or =3 mo) who were treated with flexibly dosed, once-daily solifenacin for 12 weeks. This study included subjects enrolled in VOLT who, at baseline, had urge incontinence and reported incontinence as their most bothersome symptom. All patients were started on solifenacin 5 mg/day; at week 4, the dosage could be increased to 10 mg/day and at week 8 could be maintained or decreased back to 5 mg/day. Efficacy was assessed by 3 independent patient-reported outcomes: the Patient Perception of Bladder Condition (PPBC) scale, a visual analog scale (VAS) for assessing individual symptoms, and the Overactive Bladder Questionnaire (OAB-q). RESULTS: Of the 2205 patients in the VOLT full analysis set, 1586 (71.9%) had urge incontinence at baseline, of which 582 (36.7%) reported incontinence as their most bothersome symptom. In this cohort, mean PPBC score at baseline was 4.6 (indicating moderate-to-severe problems) and at endpoint had decreased significantly to 2.9 (very minor to some minor problems; p < 0.001). At endpoint, 80.4% of patients achieved improvement in their PPBC score. These patients reported significant improvements from baseline in urinary urgency, urge incontinence, frequency, and nocturia on the VAS (p < 0.001) and all OAB-q domains (symptom severity, coping, concern, sleep, social, health-related quality of life) at endpoint (p < 0.001). CONCLUSIONS: Patients reporting urge incontinence as their most bothersome OAB symptom can be expected to demonstrate significant improvements in multiple patient-related outcomes following treatment with flexibly dosed solifenacin. PMID- 17341527 TI - Linezolid resistance in three isolates of coagulase-negative staphylococci. PMID- 17341528 TI - Olmesartan medoxomil-induced angioedema. AB - OBJECTIVE: To report a case of olmesartan medoxomil-induced angioedema in an angiotensin-converting enzyme (ACE) inhibitor-naive patient. CASE SUMMARY: A 61 year-old white woman with hypertension experienced significant swelling of her face, neck, and lips 10 days after initiation of olmesartan medoxomil 20 mg/day. After discontinuation of the drug, symptoms resolved within 10 days. Use of the Naranjo probability scale indicated a probable association between angioedema and olmesartan medoxomil. DISCUSSION: An angiotensin receptor blocker (ARB) is, in many cases, considered a safe alternative to an ACE inhibitor since serum bradykinin is thought not to be affected. However, angioedema has been reported with the use of ARBs, suggesting alternative pathways or mechanisms that result in this adverse reaction. Although not proven in humans, one explanation is that a secondary stimulation of angiotensin II AT2 receptors produces an increase in tissue bradykinin, resulting in angioedema. CONCLUSIONS: As of February 26, 2007, this is the first published reported case of olmesartan medoxomil-induced angioedema. Practitioners should be aware of this rare but potentially serious adverse event. PMID- 17341529 TI - Aliskiren for renin inhibition: a new class of antihypertensives. AB - OBJECTIVE: To review the safety, efficacy, pharmacology, pharmacokinetics, and drug interactions of aliskiren for the treatment of mild-to-moderate hypertension. DATA SOURCES: A literature search was conducted using MEDLINE (1966 January 2007), International Pharmaceutical Abstracts (1970-January 2007), and Cochrane database (2006) for the key words aliskiren or SPP100. References of selected articles were also reviewed. Abstract data were included only in the absence of significant published data. STUDY SELECTION AND DATA EXTRACTION: Available English-language data from reviews, abstracts, and clinical trials were selected. For review of efficacy, randomized controlled trials were preferred. DATA SYNTHESIS: Aliskiren is a renin inhibitor, the first in a new class of antihypertensives. As renin catalyzes the rate-limiting step of the renin angiotensin system (RAS), renin inhibition may offer a theoretical advantage over other RAS inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). In short-term clinical trials (< or =8 wk) of subjects with mild-to-moderate hypertension, single daily doses of aliskiren 150-300 mg produced significant systolic and diastolic blood pressure reduction similar to that achieved with ACE inhibitors and ARBs, with placebo-like tolerability, without an elevation in heart rate or evidence of tolerance. CONCLUSIONS: Aliskiren appears to be a safe and effective treatment option in mild-to-moderate hypertension. Although long-term outcome data have not been published, aliskiren is a promising option for RAS inhibition. PMID- 17341530 TI - The role of the pharmacist--prayer and spirituality in healing. AB - Are you a "spiritual" pharmacist? I define being spiritual as having an ongoing relationship with God regardless of whether one is physically healthy, "stressed out," or sick; I encourage pharmacists to pray for, and with, their patients when opportunities present themselves and patients are receptive. Spiritual healing can be as dramatic as physical and emotional healing. Holistic healing encompassing all 3 components is important for lasting, abundant wellness for professionals and patients alike. Spiritual practice, including a reliance on prayer in the healing process, demonstrates pharmacists' gratitude for the gifts and humility received through their relationships with patients. Imagine office based and hospital employees, from accounting, to housekeeping, to pharmacy, to nurses and physicians, praying daily. Many patients and their healthcare providers believe that faith-based prayers to God are important instruments for healing, and spiritual pharmacists may wish to consider integrating prayer into their professional practice. PMID- 17341531 TI - Retisert: is the new advance in treatment of uveitis a good one? AB - OBJECTIVE: To review the use of corticosteroids for the treatment of uveitis, with a focus on the pharmacology, efficacy, and safety of a newer delivery device, Retisert. DATA SOURCES: A PubMed/MEDLINE search from 1950 through February 2007 was conducted, and manufacturer-provided data were reviewed. STUDY SELECTION AND DATA EXTRACTION: Animal studies and Phase II and III clinical trials evaluating the safety and efficacy of Retisert for the treatment of uveitis were considered. The data were extracted from PubMed/MEDLINE using the search terms fluocinolone acetonide, corticosteroids, intravitreal implant, uveitis, ocular steroids, and Retisert. DATA SYNTHESIS: The findings of the clinical studies showed, with use of Retisert, a reduction in the recurrence of uveitis, improvement in visual acuity, and a decreased need for adjunctive therapy with corticosteroids and immunosuppressant agents. There are currently no studies directly comparing Retisert with other treatment options. The most commonly reported adverse events (ADEs) in clinical trials included cataracts, increased intraocular pressure, post-procedural complications associated with implant insertion, and ocular pain. Other ocular ADEs included decreased visual acuity, glaucoma, blurred vision, an abnormal sensation in the eye, eye irritation, and a change in tearing. These ADEs are similar to those seen with chronic corticosteroid therapy delivered by other ocular routes. CONCLUSIONS: Retisert implants have been shown to deliver sufficient drug for a longer period of time compared with the traditional steroid delivery methods. Promising efficacy results show a significant reduction in recurrence rate and improvement in visual acuity for approximately 3 years after implant. However, the drug carries the risks associated with the implant procedure and with chronic exposure of the eye to steroids. Until more data on the long-term safety are known, Retisert should be reserved for patients who are no longer tolerant of or responsive to more traditional treatment modalities. PMID- 17341532 TI - Electrocardiographic and hemodynamic effects of coenzyme Q10 in healthy individuals: a double-blind, randomized controlled trial. AB - BACKGROUND: Coenzyme Q10 (CoQ10) is an endogenous cofactor required for mitochondrial energy production and touted to treat heart failure and prevent statin-induced myopathy. In guinea pig ventricular myocytes, CoQ10 prolongs action potential duration, an effect that might prolong the QTc interval in humans. Additionally, CoQ10 reduced blood pressure in patients with essential hypertension. OBJECTIVE: To determine the electrocardiographic (ECG) and hemodynamic impact of CoQ10 in healthy individuals. METHODS: Healthy volunteers (N = 26; 62% male, age 24 +/- 3 y) were randomized to receive a single dose of CoQ10 50 mg and matching placebo in a crossover fashion with a 7 day washout period between treatments. Twelve-lead ECGs, systolic and diastolic blood pressure, and other hemodynamic parameters (cardiac index and systemic vascular resistance index) were evaluated immediately before (baseline) and 1, 3, 5, and 8 hours after ingestion of the study drug. ECG parameters (P wave and QRS complex duration; PR, QT, QTc, and RR intervals) were measured in lead II by one blinded investigator. For each time point, duplicate blood pressure levels were taken manually and then averaged. Hemodynamic parameters were measured using bioelectrical impedance cardiography. RESULTS: CoQ10 had no effect on any of the evaluated ECG parameters. The maximum postdosing systolic blood pressure showed a statistically significant increase with CoQ10 (117 +/- 10 vs 119 +/- 10 mm Hg; p = 0.037), an effect driven by increases in cardiac index (3.09 vs 2.95 L/min/m(2); p = 0.017). However, blood pressure elevation was most evident at the 5 hour timepoint (116 +/- 10 vs 113 +/- 11 mm Hg; p = 0.049) and was only transient. There were no differences between groups for maximum postdosing diastolic blood pressure. CONCLUSIONS: One dose of CoQ10 does not have any effect on ECG variables and exhibits only mild and transient effect on systolic blood pressure in young, healthy people. PMID- 17341533 TI - Low-dose ketamine in addition to propofol for procedural sedation and analgesia in the emergency department. AB - OBJECTIVE: To evaluate the efficacy and safety of low-dose intravenous ketamine in addition to intravenous propofol for procedural sedation and analgesia in the emergency department (ED). DATA SOURCES: Articles were identified using PubMed (1949-February 2007), MEDLINE (1966-February 2007), EMBASE (1980-February 2007), BioMed Central (to February 2007), the Cochrane Library (to February 2007), International Pharmaceutical Abstracts, and Google Scholar (until February 2007). Reference citations from retrieved publications were also reviewed. Search terms included ketamine, propofol, ketamine-propofol, ketofol, combination, sedation, procedural sedation, conscious sedation, and emergency department. STUDY SELECTION AND DATA EXTRACTION: All articles on prospective procedural sedation that were published or translated into English and that compared combination ketamine-propofol with an appropriate comparator group were included. Clinically relevant safety endpoints included the frequency of significant hemodynamic and respiratory compromise warranting medical intervention, nausea, vomiting, and emergence reactions. Time until hospital discharge criteria were met and patient satisfaction scores were efficacy endpoints of interest. DATA SYNTHESIS: Of the 11 trials included in this review, most had small sample sizes and were conducted in non-ED settings. The ketamine-propofol combination demonstrated no additional efficacy over propofol in terms of time to discharge. Although fewer patients given the ketamine-propofol combination experienced significant hemodynamic and respiratory compromise, need for active interventions, including fluid or vasopressor administration, supplemental oxygen, or assisted ventilation did not differ between groups. Patients who received higher doses of adjuvant ketamine reported an increased incidence of nausea, vomiting, and emergence reactions following the procedure. Few studies reported patient satisfaction scores postprocedure, and effect of ketaminepropofol on time-to-discharge criteria met was inconclusive. CONCLUSIONS: At this time, insufficient clinical evidence exists to recommend the routine use of low-dose ketamine with propofol for procedural sedation in the ED setting. PMID- 17341534 TI - Prevalence of patients using drugs metabolized by cytochrome P450 2D6 in different populations: a cross-sectional study. AB - BACKGROUND: Despite a large number of studies investigating the potential clinical relevance of CYP2D6 genotyping in preventing treatment failure (eg, insufficient efficacy and/or unacceptable adverse effects), the prevalence of patients using drugs metabolized by that isoenzyme is relatively unknown. OBJECTIVE: To investigate the prevalence of patients in different populations using drugs metabolized by CYP2D6. METHODS: In this cross-sectional study, 6 different patient populations were investigated: general, general hospital, geriatric, psychogeriatric, psychiatric, and mentally retarded. From every population, 150 adults using at least one drug were randomly selected. Primary outcome was the prevalence of patients using at least one drug metabolized by CYP2D6. The prevalence of patients using at least one CYP2D6 substrate in different populations was compared with the general population using chi(2) statistics. Data were expressed as a relative risk with a 95% confidence interval. RESULTS: Patients from the general hospital (RR 1.81; 95% CI 1.26 to 2.62), geriatric patients (RR 2.16; 95% CI 1.26 to 2.62), psychogeriatric patients (RR 2.31; 95% CI 1.63 to 3.27), and psychiatric patients (RR 2.44; 95% CI 1.73 to 3.44) were treated more frequently with at least one drug metabolized by CYP2D6 compared with patients in the general population. Approximately 50% of psychiatric (52%), psychogeriatric (49%), and geriatric (46%) patients used at least one drug metabolized by CYP2D6. In total, 416 drugs metabolized by CYP2D6 were prescribed, with 257 (62%) of these classified as an antidepressant (Anatomical and Therapeutic Chemical [ATC] category N06A) or antipsychotic (ATC N05A). CONCLUSIONS: Several patient populations (eg, psychiatric, psychogeriatric, geriatric) have a high prevalence of patients treated with at least one drug metabolized by CYP2D6. This study does not provide evidence regarding the clinical evidence of CYP2D6 genotyping, but shows that, if CYP2D6 genotyping is relevant for patient care, the highest probability of cost effectiveness will, most likely, be in specific populations. PMID- 17341535 TI - Gynecomastia associated with fenofibrate. AB - OBJECTIVE: To report a case of probable fenofibrate-induced gynecomastia. CASE SUMMARY: A 56-year-old white hypercholesterolemic man was treated with fenofibrate 160 mg/day for 1 year. During the course of treatment, he developed gynecomastia on the left side, which resolved after the drug was stopped and replaced with alpha tocopherol acetate. Sixteen months after fenofibrate discontinuation, the patient was rechallenged and subsequently developed gynecomastia symptoms on the right side. The usual etiologies of gynecomastia were excluded by careful assessment of the patient's medical history, physical examination, and results of diagnostic tests such as chest X-ray, mammography, scrotal ultrasonography, routine blood chemistry, and extensive hormonal panel. Gynecomastia again resolved after discontinuation of fenofibrate. DISCUSSION: In this case, the resolution of gynecomastia on discontinuation of fenofibrate and recurrence after rechallenge highly suggest the role of fenofibrate. Use of the Naranjo probability scale registered causality as probable. Case reports of gynecomastia caused by different drugs have been previously published, but, to our knowledge, this is the first report linking gynecomastia to the use of fenofibrate. The pathogenesis of this adverse drug reaction remains unclear. CONCLUSIONS: Although fenofibrate-induced gynecomastia appears to be uncommon, patients receiving this medication should be monitored for this adverse drug reaction. PMID- 17341536 TI - CD4+ cell count decline despite HIV suppression: a probable didanosine valganciclovir interaction. AB - OBJECTIVE: To describe a case of significant CD4+ cell decline despite complete viral suppression in an HIV-positive patient receiving didanosine and valganciclovir. CASE SUMMARY: A 68-year-old woman diagnosed with HIV and cytomegalovirus (CMV) enteritis (CD4+ cell count 22 cells/mm(3), viral load 88,898 [4.95 log] copies/mL) was treated with valganciclovir and began lamivudine, didanosine, and lopinavir/ritonavir. Three months later, her viral load was less than 50 copies/mL and CD4+ cell count was 317 cells/mm(3). Over the next 9 months, her viral load remained suppressed, but the CD4+ cell count declined to 83 cells/mm(3) and she experienced ongoing symptoms of didanosine toxicity. Didanosine was replaced with abacavir, leading to a complete CD4+ cell recovery and resolution of symptoms. DISCUSSION: Paradoxical declines in CD4+ cell counts have been reported in HIV-infected patients virally suppressed on tenofovir/didanosine regimens, presumably via inhibition of purine nucleoside phosphorylase (PNP) by tenofovir and enhancement of didanosine toxicity. Ganciclovir and its prodrug valganciclovir also inhibit PNP and increase didanosine concentrations; thus, a similar immunological effect with this combination is possible. This hypothesis is consistent with observations from a historic multicenter CMV retinitis study, where a negative CD4+ cell response was observed in patients receiving ganciclovir, while those treated with foscarnet experienced a CD4+ cell increase and a mortality advantage. Of the subjects who received any type of nucleoside therapy during this study, didanosine use was proportionally higher in the ganciclovir arm versus the foscarnet arm. According to the Naranjo probability scale, our patient experienced a probable adverse reaction associated with the combination of didanosine and valganciclovir. CONCLUSIONS: Patients receiving didanosine-containing highly active antiretroviral therapy and ganciclovir or valganciclovir for treatment of CMV infection should be monitored for didanosine toxicity and unexpected CD4+ cell loss or failure of CD4+ cell recovery. Reduction of didanosine dosage or substitution with an alternative antiretroviral may be necessary. PMID- 17341537 TI - Opioid-related adverse drug events in surgical hospitalizations: impact on costs and length of stay. AB - BACKGROUND: Opioid analgesics remain a mainstay in the treatment of pain associated with surgical procedures. Such use is associated with adverse drug events (ADEs). OBJECTIVE: To investigate the impact of opioid-related ADEs on total hospital costs and length of stay (LOS) in adult surgical patients. METHODS: This was a retrospective matched cohort study using data from computerized medical records. ADE cases were prospectively detected using computerized surveillance and verified by pharmacists. Surgical patients treated at LDS Hospital in Salt Lake City from January 1, 1998, to December 31, 2003, were included. The primary outcomes were costs and hospital LOS associated with opioid-related ADEs and the relationship of opioid dose to ADE events. RESULTS: Patients experiencing opioid-related ADEs had significantly increased median total hospital costs (7.4% increase; 95% CI 3.83 to 10.96; p < 0.001) and increased median LOS (10.3% increase; 95% CI 6.5 to 14.2; p < 0.001) compared with matched non-ADE controls. The increased costs attributable to ADEs, by surgery type, were general surgery ($676.51; 95% CI 351.50 to 1001.50), orthopedics ($861.50; 95% CI 448.20 to 1274.80), and obstetrics/gynecology ($540.90; 95% CI 281.40 to 800.40). Similarly, increased LOS attributable to ADEs, by surgery type, were general surgery (0.64 days; 95% CI 0.40 to 0.88), orthopedics (0.52 days; 95% CI 0.33 to 0.71), and obstetrics/gynecology (0.53 days; 95% CI 0.33 to 0.72). Higher doses of opioids were associated with increased risk of experiencing ADEs (OR 1.3; 95% CI 1.07 to 1.60; p = 0.01). CONCLUSIONS: Opioid-related ADEs following surgery were associated with significantly increased LOS and hospitalization costs. These ADEs occurred more frequently in patients receiving higher doses of opioids. PMID- 17341538 TI - Universal versus selective iron supplementation for infants and the risk of unintentional poisoning in young children: a comparative study of two populations. AB - BACKGROUND: Iron continues to be a common cause of poisoning in young children, in part due to its widespread use and easy accessibility. OBJECTIVE: To determine differences in the epidemiology and outcome of unintentional iron ingestion by young children in populations practicing selective (eg, US) versus universal (eg, Israel) iron supplementation to infants. METHODS: All cases of unintentional iron ingestion in children younger than 7 years in a one year period were identified through the poison control center databases of 2 sites (Illinois and Israel). Parameters compared include patient sex and age; type, form, and dose of iron preparation; circumstances and clinical manifestations; management; and outcome. RESULTS: A total of 602 children were identified: 459 in Illinois and 143 in Israel. The majority of Illinois children ingested multivitamin preparations (94%), whereas Israeli children ingested single-ingredient iron preparations (78%) (p < 0.001). Iron doses ingested were higher in Israel (median 14.5 vs 6.6 mg/kg; p < 0.001) but remained within the nontoxic range for most children. No deaths or severe poisonings were reported, and 93% of children in both groups were asymptomatic. The majority of ingestions in both locations were due to unintentional self-ingestion. However, parental miscalculation occurred more frequently in Israel (16%) than in Illinois (1%). CONCLUSIONS: Universal iron supplementation to infants was not associated with a negative impact on the outcome of pediatric unintentional ingestions. Low-dose exposures were safely managed by on-site observation. PMID- 17341539 TI - Bupropion therapy for pathological gambling. PMID- 17341540 TI - Lercanidipine in the treatment of hypertension. AB - OBJECTIVE: To review the literature regarding the efficacy, tolerability, and utility of lercanidipine in the treatment of hypertension. DATA SOURCES: A search of the literature was performed using MEDLINE (1966-September 2006), EMBASE Drugs and Pharmacology (1980-September 2006), and Current Contents/Clinical Medicine (week 24, 2005-week 30, 2006). Package inserts from lercanidipine, nifedipine, felodipine, and amlodipine were also reviewed for comparison of adverse effects. STUDY SELECTION AND DATA EXTRACTION: Articles were limited to clinical trials, abstracts, and review articles published in English. DATA SYNTHESIS: Lercanidipine is a novel dihydropyridine (DHP) calcium-channel blocker indicated for the treatment of mild-to-moderate hypertension. Although it is not yet available in the US, lercanidipine has been utilized extensively in other countries. In 2 randomized controlled trials of approximately 400 patients with mild-to-moderate hypertension, lercanidipine showed efficacy similar to that of 2 other DHPs, felodipine and slow-release nifedipine, in significantly reducing systolic blood pressure and diastolic blood pressure (DBP) after 4 weeks. In a longer trial (12 mo), lercanidipine 10 mg/day led to normalized blood pressure in 49% of patients after 4 weeks. A postmarketing trial of 9050 patients corroborated the results observed in previous clinical trials, with 64% of patients achieving a DBP of less than 90 mm Hg and 32% attaining blood pressure control (<140/90 mm Hg). In elderly patients, lercanidipine was found comparable with lacidipine and nifedipine, showing similar decreases in DBP when compared with nifedipine (-18.3 vs -17.7 mm Hg, respectively). What distinguishes lercanidipine from other members of the DHP class is its lower incidence of adverse effects, particularly edema. One study showed that fewer patients withdrew secondary to adverse drug reactions in the lercanidipine (0.9%) and nifedipine (3.8%) group compared with the felodipine (4.5%) group. Lercanidipine has also shown efficacy similar to that of other antihypertensives, including atenolol, captopril, and losartan. CONCLUSIONS: Lercanidipine may be an option in the treatment of hypertension, as current literature suggests comparable antihypertensive efficacy and better tolerability. Further randomized, double blind clinical trials must be conducted in order to clarify its position among other antihypertensive medications. PMID- 17341541 TI - Chlorpromazine-associated antiphospholipid antibody syndrome. PMID- 17341542 TI - Magnetic resonance colonography without bowel cleansing: a prospective cross sectional study in a screening population. AB - BACKGROUND AND AIMS: To evaluate the diagnostic accuracy of magnetic resonance colonography (MRC) without bowel cleansing in a screening population and compare the results to colonoscopy as a standard of reference. METHODS: 315 screening patients, older than 50 years with a normal risk profile for colorectal cancer, were included in this study. For MRC, a tagging agent (5.0% Gastrografin, 1.0% barium sulphate, 0.2% locust bean gum) was ingested with each main meal within 2 days prior to MRC. No bowel cleansing was applied. For the magnetic resonance examination, a rectal water enema was administered. Data collection was based on contrast enhanced T1 weighted images and TrueFISP images. Magnetic resonance data were analysed for image quality and the presence of colorectal lesions. Conventional colonoscopy and histopathological samples served as reference. RESULTS: In 4% of all colonic segments, magnetic resonance image quality was insufficient because of untagged faecal material. Adenomatous polyps >5 mm were detected by means of MRC, with a sensitivity of 83.0%. Overall specificity was 90.2% (false positive findings in 19 patients). However, only 16 of 153 lesions <5 mm and 9 of 127 hyperplastic polyps could be visualised on magnetic resonance images. CONCLUSIONS: Faecal tagging MRC is applicable for screening purposes. It provides good accuracy for the detection of relevant (ie, adenomatous) colorectal lesions >5 mm in a screening population. However, refinements to optimise image quality of faecal tagging are needed. PMID- 17341543 TI - Age and comorbidity as risk factors for vocal cord paralysis associated with tracheal intubation. AB - BACKGROUND: Vocal cord paralysis after tracheal intubation may be attributed to ageing and comorbidity. However, the relationship between patient characteristics and the risk of vocal cord paralysis is unknown. METHODS: We prospectively analysed data representing 31 241 consecutive surgery patients who underwent tracheal intubation to determine whether duration of intubation, age, sex, and cardiovascular, cerebrovascular, and metabolic diseases were risk factors for vocal cord paralysis associated with intubation. Patients with vocal cord paralysis from any other causes were excluded. RESULTS: Twenty-four (0.077%) suffered vocal cord paralysis (left, 16 patients; right, 8 patients). The risk was increased when intubation lasted 3-6 h (odds ratio, 2.0; 95% confidence interval, 1.1-5.6; P = 0.002) or 6 h or more (odds ratio, 14.5; 95% confidence interval, 5.2-40.9; P < 0.0001). The risk was increased in patients aged 50-69 (odds ratio, 3.6; 95% confidence interval, 1.2-11.1; P = 0.02) and 70 yr or above (odds ratio, 3.9; 95% confidence interval, 1.2-12.8; P = 0.02). The risk was increased with diabetes mellitus (odds ratio, 2.5; 95% confidence interval, 1.1 7.3; P = 0.03) and hypertension (odds ratio, 2.1; 95% confidence interval, 1.1 6.0; P = 0.03). CONCLUSIONS: The risk of vocal cord paralysis was increased three fold in patients aged 50 or above, two-fold in patients intubated 3-6 h, 15-fold in patients intubated 6 h or more, and two-fold in patients with a history of diabetes mellitus or hypertension. Our results are informative for informed consent, patient counselling, and intubation decision-making. PMID- 17341544 TI - Regulation of human organic anion transporter 4 by progesterone and protein kinase C in human placental BeWo cells. AB - Human organic anion transporter 4 (hOAT4) belongs to a family of organic anion transporters that play critical roles in the body disposition of clinically important drugs, including anti-human immunodeficiency virus therapeutics, anti tumor drugs, antibiotics, antihypertensives, and anti-inflammatories. hOAT4 is abundantly expressed in the placenta. In the current study, we examined the regulation of hOAT4 by pregnancy-specific hormones progesterone (P(4)) and 17beta estradiol (E(2)) and by protein kinase C (PKC) in human placental BeWo cells. P(4) induced a time- and concentration-dependent downregulation of hOAT4 transport activity, whereas E(2) had no effect on hOAT4 function. The downregulation of hOAT4 activity by P(4) mainly resulted from a decreased cell surface expression without a change in total cell expression of the transporter, kinetically revealed as a decreased V(max) without significant change in K(m). Activation of PKC by phorbol 12,13-dibutyrate also resulted in an inhibition of hOAT4 activity through a decreased cell surface expression of the transporter. However, P(4)-induced downregulation of hOAT4 activity could not be prevented by treating hOAT4-expressing cells with the PKC inhibitor staurosporine. We concluded that both P(4) and activation of PKC inhibited hOAT4 activity through redistribution of the transporter from cell surface to the intracellular compartments. However, P(4) regulates hOAT4 activity by mechanisms independent of PKC pathway. PMID- 17341545 TI - Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables. AB - The aim of the current investigation was to determine the possible relationships of fasting adiponectin level with body composition, bone mineral, insulin sensitivity, leptin, and cardiorespiratory fitness parameters in 153 women. Subjects were classified as premenopausal (n = 42; 40.8 +/- 5.7 yr) if they had regular menstrual periods, early postmenopausal (n = 49; 56.7 +/- 3.6 yr) if they had been postmenopausal for more than >1 yr but <7 yr (5.5 +/- 1.3 yr), and postmenopausal (n = 62; 72.2 +/- 4.5 yr) if they had been postmenopausal for >7 yr. All women studied had a body mass index (BMI) <30 kg/m(2). Adiponectin values were higher (P < 0.05) in middle-aged (12.0 +/- 5.1 microg/ml) and older (15.3 +/ 7.3 microg/ml) postmenopausal women compared with middle-aged premenopausal women (8.4 +/- 3.2 microg/ml). Mean plasma adiponectin concentration in the total group of women (n = 153) was 12.2 +/- 6.3 microg/ml and was positively related (P < 0.05) to age, indexes of overall obesity (BMI, body fat mass), and cardiorespiratory fitness (PWC) values. In addition, a negative association (P < 0.05) between adiponectin with central obesity (waist-to-hip and waist-to-thigh ratio), fat-free mass, bone mineral (bone mineral content, total and lumbar spine bone mineral density), and leptin and insulin resistance (insulin, fasting insulin resistance index) values was observed. However, multivariate regression analysis revealed that only age, fasting insulin resistance index, and leptin were independent predictors of adiponectin concentration. In conclusion, circulating adiponectin concentrations increase with age in normal-weight middle aged and older women. It appears that adiponectin is independently related to age, leptin, and insulin resistance values in women across the age span and menstrual status. PMID- 17341546 TI - NEFA-glucose comodulation model of beta-cell insulin secretion in 24-h multiple meal test. AB - There is experimental evidence that a source of fatty acids (FAs) that is either exogenous or endogenous is necessary to support normal insulin secretion. Therefore, FAs comodulate the glucose-induced pancreatic insulin secretion. To assess the role of FAs, 16 morbidly obese nondiabetic patients and 6 healthy volunteers were studied. The controls and the obese subjects, before and after diet-induced weight loss, spent 24 h in a calorimetric chamber, where they consumed standardized meals. Hourly blood samples were drawn from a central venous catheter for the measurement of glucose, C-peptide, and nonesterified fatty acid (NEFA) concentrations. Insulin sensitivity was measured (as the M value) by euglycemic hyperinsulinemic clamp. In the present study, we propose a mathematical model in which insulin secretion rate (ISR) is expressed as a function of both plasma glucose and NEFA concentrations. Model parameters, obtained by fitting the individual experimental data of plasma C-peptide concentration, gave an estimated ISR comparable with that obtained by the deconvolution method. To evaluate the performance of the model in an experimental condition in which incretin effect was minimized, previous data on insulin secretion following a butter load and subsequent hyperglycemic clamp were reanalyzed. This model of nutrient-stimulated insulin secretion is the first attempt to represent in a simple way the interaction between glucose and NEFA in the regulation of insulin secretion in the beta-cell and explains, at least in part, the "potentiation factor" used in previous models to account for other control factors different from glucose after either an intravenous infusion of glucose or a mixed meal. PMID- 17341547 TI - Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance. AB - Elevated oxidative capacity, such as occurs via endurance exercise training, is believed to protect against the development of obesity and diabetes. Rats bred both for low (LCR)- and high (HCR)-capacity endurance running provide a genetic model with inherent differences in aerobic capacity that allows for the testing of this supposition without the confounding effects of a training stimulus. The purpose of this investigation was to determine the effects of a high-fat diet (HFD) on weight gain patterns, insulin sensitivity, and fatty acid oxidative capacity in LCR and HCR male rats in the untrained state. Results indicate chow fed LCR rats were heavier, hypertriglyceridemic, less insulin sensitive, and had lower skeletal muscle oxidative capacity compared with HCR rats. Upon exposure to an HFD, LCR rats gained more weight and fat mass, and their insulin resistant condition was exacerbated, despite consuming similar amounts of metabolizable energy as chow-fed controls. These metabolic variables remained unaltered in HCR rats. The HFD increased skeletal muscle oxidative capacity similarly in both strains, whereas hepatic oxidative capacity was diminished only in LCR rats. These results suggest that LCR rats are predisposed to obesity and that expansion of skeletal muscle oxidative capacity does not prevent excess weight gain or the exacerbation of insulin resistance on an HFD. Elevated basal skeletal muscle oxidative capacity and the ability to preserve liver oxidative capacity may protect HCR rats from HFD-induced obesity and insulin resistance. PMID- 17341548 TI - c-Myc and ChREBP regulate glucose-mediated expression of the L-type pyruvate kinase gene in INS-1-derived 832/13 cells. AB - Increased glucose flux generates metabolic signals that control transcriptional programs through poorly understood mechanisms. Previously, we demonstrated a necessity in hepatocytes for c-Myc in the regulation of a prototypical glucose responsive gene, L-type pyruvate kinase (L-PK) (Collier JJ, Doan TT, Daniels MC, Schurr JR, Kolls JK, Scott DK. J Biol Chem 278: 6588-6595, 2003). Pancreatic beta cells have many features in common with hepatocytes with respect to glucose regulated gene expression, and in the present study we determined whether c-Myc was required for the L-PK glucose response in insulin-secreting (INS-1)-derived 832/13 cells. Glucose increased c-Myc abundance and association with its heterodimer partner, Max. Manipulations that prevented the formation of a functional c-Myc/Max heterodimer reduced the expression of the L-PK gene. In addition, glucose augmented the binding of carbohydrate response element binding protein (ChREBP), c-Myc, and Max to the promoter of the L-PK gene in situ. The transactivation of ChREBP, but not of c-Myc, was dependent on high glucose concentrations in the contexts of either the L-PK promoter or a heterologous promoter. The glucose-mediated transactivation of ChREBP was independent of mutations that alter phosphorylation sites thought to regulate the cellular location of ChREBP. We conclude that maximal glucose-induced expression of the L PK gene in INS-1-derived 832/13 cells involves increased c-Myc abundance, recruitment of c-Myc, Max, and ChREBP to the promoter, and a glucose-stimulated increase in ChREBP transactivation. PMID- 17341549 TI - Stevioside improves pancreatic beta-cell function during glucotoxicity via regulation of acetyl-CoA carboxylase. AB - Chronic hyperglycemia is detrimental to pancreatic beta-cells, causing impaired insulin secretion and beta-cell turnover. The characteristic secretory defects are increased basal insulin secretion (BIS) and a selective loss of glucose stimulated insulin secretion (GSIS). Several recent studies support the view that the acetyl-CoA carboxylase (ACC) plays a pivotal role for GSIS. We have shown that stevioside (SVS) enhances insulin secretion and ACC gene expression. Whether glucotoxicity influences ACC and whether this action can be counteracted by SVS are not known. To investigate this, we exposed isolated mouse islets as well as clonal INS-1E beta-cells for 48 h to 27 or 16.7 mM glucose, respectively. We found that 48-h exposure to high glucose impairs GSIS from mouse islets and INS 1E cells, an effect that is partly counteracted by SVS. The ACC dephosphorylation inhibitor okadaic acid (OKA, 10(-8) M), and 5-aminoimidazole-4-carboxamide-1-beta d-ribofuranoside (AICAR, 10(-4) M), an activator of 5'-AMP protein kinase that phosphorylates ACC, eliminated the beneficial effect of SVS. 5-Tetrade-cyloxy-2 furancarboxylic acid (TOFA), the specific ACC inhibitor, blocked the effect of SVS as well. During glucotoxity, ACC gene expression, ACC protein, and phosphorylated ACC protein were increased in INS-1E beta-cells. SVS pretreatment further increased ACC gene expression with strikingly elevated ACC activity and increased glucose uptake accompanied by enhanced GSIS. Our studies show that glucose is a potent stimulator of ACC and that SVS to some extent counteracts glucotoxicity via increased ACC activity. SVS possesses the potential to alleviate negative effects of glucotoxicity in beta-cells via a unique mechanism of action. PMID- 17341550 TI - Infusion of a biotinylated bis-glucose photolabel: a new method to quantify cell surface GLUT4 in the intact mouse heart. AB - Glucose uptake in the heart is mediated by specific glucose transporters (GLUTs) present on cardiomyocyte cell surface membranes. Metabolic stress and insulin both increase glucose transport by stimulating the translocation of glucose transporters from intracellular storage vesicles to the cell surface. Isolated perfused transgenic mouse hearts are commonly used to investigate the molecular regulation of heart metabolism; however, current methods to quantify cell surface glucose transporter content in intact mouse hearts are limited. Therefore, we developed a novel technique to directly assess the cell surface content of the cardiomyocyte glucose transporter GLUT4 in perfused mouse hearts, using a cell surface impermeant biotinylated bis-glucose photolabeling reagent (bio-LC-ATB BGPA). Bio-LC-ATB-BGPA was infused through the aorta and cross-linked to cell surface GLUTs. Bio-LC-ATB-BGPA-labeled GLUT4 was recovered from cardiac membranes by streptavidin isolation and quantified by immunoblotting. Bio-LC-ATB-BGPA labeling of GLUT4 was saturable and competitively inhibited by d-glucose. Stimulation of glucose uptake by insulin in the perfused heart was associated with parallel increases in bio-LC-ATB-BGPA-labeling of cell surface GLUT4. Bio-LC ATB-BGPA also labeled cell surface GLUT1 in the perfused heart. Thus, photolabeling provides a novel approach to assess cell surface glucose transporter content in the isolated perfused mouse heart and may prove useful to investigate the mechanisms through which insulin, ischemia, and other stimuli regulate glucose metabolism in the heart and other perfused organs. PMID- 17341551 TI - Activation of AMP-activated protein kinase stimulates proopiomelanocortin gene transcription in AtT20 corticotroph cells. AB - Starvation is known to activate the hypothalamo-pituitary-adrenal (HPA) axis, a representative antistress system in the living organism. In this study, we investigated in vitro whether activation of the AMP-activated protein kinase (AMPK), which is known to occur in intracellular energy depletion, influences the expression of POMC gene that encodes adrenocorticotropin. We first confirmed that each subunit of AMPK was expressed in the AtT20 corticotroph cell line. We then found that AICAR, a cell-permeable AMP analog and an activator of AMPK, potently stimulated the 5'-promoter activity of POMC gene in a dose-dependent manner. The effects were promoter specific because AICAR enhanced the AP1-mediated POMC promoter activities but did not influence other transcription factor-induced transcription. The effect of AICAR on POMC gene transcription was completely eliminated by specific AMPK inhibitor compound C or by dominant negative AMPK, whereas overexpression of constitutively active AMPK mimicked the effect of AICAR. Finally, experiments using specific kinase inhibitors suggested that the PI 3-kinase-mediated signaling pathway is at least partly involved in the effect. Our results suggest that intracellular energy depletion with the resultant activation of AMPK directly stimulates the HPA axis at the pituitary level by increasing the expression of POMC gene. PMID- 17341552 TI - Assessment of beta-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests. AB - Assessment of insulin secretion in humans under physiological conditions has been a challenge because of its complex interplay with insulin action and hepatic insulin extraction. The possibility of simultaneously assessing beta-cell function, insulin sensitivity, and hepatic insulin extraction under physiological conditions using a simple protocol is appealing, since it has the potential to provide novel insights regarding the regulation of fasting and postprandial glucose metabolism in diabetic and nondiabetic humans. In this Perspective, we review data indicating that an oral glucose tolerance test (OGTT) or a meal test is able to accomplish this goal when interpreted with the oral beta-cell minimal model. We begin by using the well-established intravenous minimal model to highlight how the oral minimal model was developed and how the oral assessment parallels that of an intravenous glucose tolerance test (IVGTT). We also point out the unique aspects of both approaches in relation to their ability to assess different aspects of the beta-cell secretory cascade. We review the ability of the oral model to concurrently measure insulin sensitivity and hepatic insulin extraction, thereby enabling it to quantitatively portray the complex relationship among beta-cell function, hepatic insulin extraction, and insulin action. In addition, data from 204 individuals (54 young and 159 elderly) who underwent both IVGTT and meal tolerance tests are used to illustrate how these different approaches provide complementary but differing insights regarding the regulation of beta-cell function in humans. PMID- 17341553 TI - Stress responsiveness in adult life: influence of mother's diet in late pregnancy. AB - CONTEXT: Men and women whose mothers ate an unbalanced high-protein, low carbohydrate diet in late pregnancy have raised blood pressure. We recently showed that they also have raised fasting plasma cortisol concentrations. Because raised fasting cortisol concentrations probably reflect a greater response to the stress of fasting and venesection, we suspected that this diet may have led to increased stress responsiveness in the adult offspring. OBJECTIVE: The aim was to determine whether an unbalanced high-protein diet during pregnancy is associated with increased cortisol secretion in response to psychological stress in the offspring. DESIGN AND PARTICIPANTS: Salivary cortisol concentrations were measured during a modified Trier Social Stress Test in 70 men and women aged 36.3 yr whose mothers had taken part in a dietary intervention in which they were advised to eat 1 pound (0.45 kg) of red meat daily during pregnancy and to avoid carbohydrate-rich foods. RESULTS: The offspring of women who reported greater consumption of meat and fish in the second half of pregnancy had higher cortisol concentrations during the Trier Test. Compared with the offspring of mothers who had reported eating no more than 13 meat/fish portions per week, the average cortisol concentrations were raised by 22% (95% confidence interval, 13 to 71%) and 46% (5 to 103%) in the offspring of those eating 14-16 and at least 17 portions per week, respectively. CONCLUSIONS: These findings provide the first human evidence that an unbalanced high protein maternal diet during late pregnancy leads to increased cortisol secretion in response to psychological stress in the offspring. PMID- 17341554 TI - Prevalence and functional significance of antipituitary antibodies in patients with autoimmune and non-autoimmune thyroid diseases. AB - BACKGROUND: Circulating antipituitary antibodies (APA) are markers of autoimmune hypophysitis, which may cause deficient pituitary function. The prevalence of APA in autoimmune thyroid disorders (AITD) is uncertain. OBJECTIVES: The aims of this study were 1) to evaluate APA prevalence in a large series of patients with AITD and non-AITD and 2) to investigate the functional significance of APA by assessing pituitary function in APA-positive patients. DESIGN AND SETTING: We conducted a health survey on consecutive AITD and non-AITD patients at a tertiary referral center (Department of Endocrinology, Pisa). PATIENTS: Subjects, including 1290 consecutive patients with thyroid disorders (961 AITD and 329 non AITD) and 135 controls, were enrolled in the study. METHODS: APA (indirect immunofluorescence), free T(4), free T(3), TSH, and organ-specific autoantibodies were assayed in all patients. Functional pituitary evaluation was performed in most APA-positive patients. RESULTS: APA frequency was higher in AITD (11.4%) than in non-AITD (0.9%; P < 0.0001) patients; all control subjects had negative APA tests. APA were more frequently found in Hashimoto's thyroiditis (13%) than in Graves' disease (7.1%; P = 0.05). Of 110 APA-positive AITD patients, 20 (18.2%) had autoimmune polyglandular syndrome, whereas 90 (81.8%) had apparently isolated AITD. APA positivity increased percentage of autoimmune polyglandular syndrome in our series from 10.4 to 13.5%. Of 110 APA-positive patients, 102 were submitted to dynamic testing for functional pituitary assessment; 36 patients (35.2%) had mild or severe GH deficiency (GHD). No additional anterior pituitary hormone deficiencies were found; one patient had central diabetes insipidus. Pituitary abnormalities at magnetic resonance imaging were found in most APA positive GHD patients. CONCLUSIONS: APA are frequently present in patients with AITD. Patients should be tested for APA because positive tests are associated with GHD. PMID- 17341555 TI - Dose-response effects of free fatty acids on glucose and lipid metabolism during somatostatin blockade of growth hormone and insulin in humans. AB - CONTEXT: GH and other stress hormones stimulate lipolysis, which may result in free fatty acid (FFA)-mediated insulin resistance. However, there are also indications that FFAs in the very low physiological range have the same effect. OBJECTIVE: The objective of the study was to address systematically the dose response relations between FFAs and insulin sensitivity. DESIGN: We therefore examined eight healthy men for 8 h (6 h basal and 2 h glucose clamp) on four occasions. INTERVENTION: Intralipid was infused at varying rates (0, 3, 6, 12 microl.kg(-1).min(-1)); lipolysis was blocked by acipimox; and endogenous GH, insulin, and glucagon secretion was blocked by somatostatin and subsequently replaced at fixed rates. RESULTS: This resulted in four different FFA levels between 50 and 2000 micromol/liter, with comparable levels of insulin and counterregulatory hormones. Both in the basal state and during insulin stimulation, we saw progressively decreased glucose disposal, nonoxidative glucose disposal, and forearm muscle glucose uptake at FFA levels above 500 micromol/liter. Apart from forearm glucose uptake, the very same parameters were decreased at low FFA levels (approximately 50 micromol/liter). FFA rate of disposal was linearly related to the level of FFAs, whereas lipid oxidation reached a maximum at FFA levels approximately 1000 micromol/liter. CONCLUSION: In the presence of comparable levels of all major metabolic hormones, insulin sensitivity peaks at physiological levels of FFAs with a gradual decrease at elevated as well as suppressed FFA concentrations. These data constitute comprehensive dose-response curves for FFAs in the full physiological range from close to zero to above 2000 micromol/liter. PMID- 17341556 TI - Nuclear progesterone receptors in the human pregnancy myometrium: evidence that parturition involves functional progesterone withdrawal mediated by increased expression of progesterone receptor-A. AB - CONTEXT: We examined whether human parturition involves functional progesterone withdrawal mediated by changes in myometrial expression of progesterone receptors (PRs)-A and -B. OBJECTIVE: Our objectives were to: 1) measure PR-A and PR-B protein levels in human pregnancy myometrium and determine whether the PR-A to PR B ratio changes with advancing gestation and labor onset; and 2) determine how changes in the PR-A to PR-B ratio affect myometrial cell progesterone responsiveness. DESIGN: PR protein levels and cellular localization were measured by Western blotting and immunohistochemistry, respectively, in lower uterine segment uterine wall tissue from preterm (<37 wk; not laboring; n = 5) and term (37-40 wk; not in labor: n = 6; in labor: n = 5) cesarean delivery. The capacity for PR-A and PR-B, alone and in combination, to mediate genomic progesterone responsiveness measured by the activity of a progesterone-responsive reporter plasmid was examined by artificially modulating their levels in the PHM1-31 myometrial cell line. RESULTS: PR-A and PR-B immunostaining was detected only in the nucleus of myometrial cells. The PR-A to PR-B protein ratio was 0.49 +/- 0.082 (mean +/- sem) in preterm tissue; increased to 1.03 +/- 0.071 (P < 0.001) in nonlaboring term tissue; and increased further to 2.65 +/- 0.344 (P < 0.001) in laboring term tissue. Only PR-B mediated progesterone-induced transcriptional activity. PR-A had no effect alone but markedly decreased PR-B-mediated progesterone responsiveness. CONCLUSIONS: Functional progesterone withdrawal in human parturition may be mediated by an increase in the myometrial PR-A to PR-B ratio due to increased PR-A expression. PMID- 17341557 TI - Formation of ethinyl estradiol in women during treatment with norethindrone acetate. AB - CONTEXT: The significance of the conversion of norethindrone acetate (NET-A), a commonly prescribed, synthetic, oral progestogen, to ethinyl estradiol (EE(2)) is controversial. OBJECTIVE: We sought to determine accurately the extent to which NET-A may be converted to EE(2), and if so, whether circulating levels of EE(2) would be of clinical significance. DESIGN, SUBJECTS, AND INTERVENTIONS: We administered NET-A 10, 20, or 40 mg once daily for 7 d to 20 regularly menstruating premenopausal women and measured NET-A and EE(2) levels before drug intake; at 1, 2, 4, 8, and 24 h after the first dose; and 2 h after the seventh dose. RESULTS: The mean EE(2) maximum serum concentration obtained from the 10-, 20-, and 40-mg doses of NET-A in this study is 58, 178, and 231 pg/ml, respectively. The conversion ratio of NET-A to EE(2) ranged from 0.20 to 0.33% for the different doses. CONCLUSIONS: NET-A is converted to EE(2), and although the conversion rate is relatively small, higher doses of NET-A, as used clinically, give rise to substantial levels of EE(2). PMID- 17341558 TI - Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. AB - CONTEXT: Retinol binding protein (RBP4), secreted primarily from the liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity, its relationship with subclinical inflammation, and its response to lifestyle changes are not elucidated. OBJECTIVE: The objective of the study was to determine in children: 1) the status of RBP4 levels in lean vs. obese; 2) the relationship between RBP4 levels and subclinical inflammation; and 3) the effect of lifestyle-only intervention on RBP4 levels. DESIGN, SETTING, AND PATIENTS: Lean and obese children (n = 21) matched for age (>14 yr to < 18 yr) and maturity stage (Tanner IV) were studied at baseline and with lifestyle intervention in obese subjects only (n = 15). INTERVENTION: Patients received 3 months of randomized and controlled physical activity-based lifestyle intervention. MAIN OUTCOME MEASURE: RBP4 levels in children before and after intervention and the relationship between RBP4 and subclinical inflammation were measured. RESULTS: Higher RBP4 levels were found in the obese group vs. lean group (P = 0.005). RBP4 correlated with not only indices of obesity and insulin resistance but also inflammatory factors (r = 0.63 and 0.64 for C-reactive protein and IL-6, respectively, P < 0.01). Intervention reduced RBP4 levels by approximately 30% (P = 0.001), and RBP4 reduction was correlated with the magnitude of decrease in inflammatory factors (P = 0.01). CONCLUSION: Alterations in serum RBP4 occur at an early age in the clinical course of obesity and appear to correlate with subclinical inflammation. Lifestyle intervention almost entirely reversed the raised RBP4 levels in obese children. Future studies should determine whether elevation of RBP4 is a direct trigger for the insulin resistance and subclinical inflammation implicated in the premature development of cardiovascular disease and diabetes. PMID- 17341559 TI - Aromatase expression in uterine leiomyomata is regulated primarily by proximal promoters I.3/II. AB - CONTEXT: Uterine leiomyomata are common tumors that cause irregular uterine bleeding and pregnancy loss and depend on estrogen for growth. Aromatase catalyzes the conversion of androgens to estrogens. Aromatase expression is regulated via alternatively used promoters in the placenta (I.1 and I.2a), fat (I.4, I.3, and II), bone (I.6), and gonads (II). A prostaglandin E(2)/cAMP dependent pathway regulates coordinately the proximal promoters I.3/II, whereas glucocorticoids and cytokines regulate the distal promoter I.4. Use of each promoter gives rise to a population of aromatase mRNA species with unique 5' untranslated regions (5'-UTRs). Uterine leiomyoma tissue, but not normal myometrium, overexpresses aromatase leading to estrogen-stimulated cell proliferation. Aromatase inhibitor treatment shrank uterine leiomyomata in a few women. OBJECTIVE AND DESIGN: Promoter I.4 was reported to regulate aromatase expression in uterine leiomyomata from a group of Japanese women. Here, we used two independent techniques to identify the promoters that regulate aromatase expression in uterine leiomyomata (n = 30) from 23 African-American, Hispanic, and white women. RESULTS: Rapid amplification of 5'-cDNA ends of aromatase mRNA species revealed the following distribution of promoter usage in leiomyomata: promoters I.3/II, 61.5%; I.2a, 15.4%; I.6, 15.4%; and I.4, 7.7%. Real-time PCR, which quantifies mRNA species with promoter-specific 5'-UTRs, revealed the following distribution for each 5'-UTR as a fraction of total aromatase mRNA: I.3/II, 69.6%; I.4, 7.3%; and other promoters, 23.1%. CONCLUSIONS: The primary in vivo aromatase promoter in leiomyoma tissues in non-Asian U.S. women is the prostaglandin E(2)/cAMP-responsive I.3/II region. Alternative signals may stimulate aromatase expression that is a common biological phenotype in uterine leiomyomata. PMID- 17341560 TI - Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma. AB - CONTEXT: Acromegaly is usually sporadic, but familial cases occur in association with several familial pituitary tumor syndromes. Recently mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were associated with familial pituitary adenoma predisposition. OBJECTIVE: The objective of the study was to investigate the status of AIP in a pituitary tumor predisposition family. SETTINGS: The study was conducted at a nonprofit academic center and medical centers. PATIENTS: Eighteen members of a Brazilian family with acromegaly were studied. RESULTS: A novel germline mutation in the AIP gene, Y268X, predicted to generate a protein lacking two conserved domains, was identified in four members of this family: two siblings with early-onset acromegaly; a third, 41-yr-old sibling with a microadenoma but no clinical features of disease, and his 3-yr-old son. No changes were found in 14 unaffected at-risk relatives or 92 healthy controls. CONCLUSIONS: We confirm the role of the AIP gene in familial acromegaly. This finding increases the spectrum of molecular defects that can give rise to pituitary adenoma susceptibility. Establishment of genotype phenotype correlations in AIP mutant tumors will determine whether AIP screening can be used as a tool for clinical surveillance and genetic counseling of families with pituitary tumor predisposition. The underlying basis for the phenotypic variation within AIP-mutant families and the mechanism of AIP-mediated tumorigenesis remain to be defined. PMID- 17341561 TI - Measurement of serum free cortisol shows discordant responsivity to stress and dynamic evaluation. AB - CONTEXT: Routinely available assays of adrenal function measure serum total cortisol (TC) and not the biologically active free cortisol (FC). However, there are few data on FC levels during surgical stress and in response to standard pharmacological tests. OBJECTIVE: Our objective was to evaluate TC and FC levels in different states of physical stress. DESIGN AND SETTING: We conducted a prospective observational study in a university hospital. PARTICIPANTS AND MAIN OUTCOME MEASURES: We measured TC and FC levels in 64 patients: group A, 17 healthy controls without stress; group B, 23 medical patients with moderate stress; and group C, 24 surgical patients undergoing coronary bypass grafting. Cortisol levels in group C were measured basally and at several time points thereafter and were compared with responsivity to a pharmacological dose of ACTH. FC was measured using equilibrium dialysis. RESULTS: In group C patients after extubation, the relative increase above basal FC was higher than the increase in TC levels (399 +/- 266 vs. 247 +/- 132% of initial values, respectively; mean +/- sd; P = 0.02) and then fell more markedly, FC levels falling to 67 +/- 49% and TC levels to 79 +/- 36% (P = 0.04). After ACTH stimulation, TC levels increased to 680 +/- 168 nmol/liter, which was similar to the increase with major stress (811 +/- 268 nmol/liter). In contrast, FC levels increased to 55 +/- 16 nmol/liter after ACTH stimulation but significantly greater with surgical stress to 108 +/- 56 nmol/liter (P < 0.001). CONCLUSION: The more pronounced increase in FC seen during stress as compared with the ACTH test suggests that this test does not adequately anticipate the FC levels needed during severe stress. PMID- 17341562 TI - The impact of pegvisomant treatment on substrate metabolism and insulin sensitivity in patients with acromegaly. AB - CONTEXT: Pegvisomant is a specific GH receptor antagonist that is able to normalize serum IGF-I concentrations in most patients with acromegaly. The impact of pegvisomant on insulin sensitivity and substrate metabolism is less well described. PATIENTS AND METHODS: We assessed basal and insulin-stimulated (euglycemic clamp) substrate metabolism in seven patients with active acromegaly before and after 4-wk pegvisomant treatment (15 mg/d) in an open design. RESULTS: After pegvisomant, IGF-I decreased, whereas GH increased (IGF-I, 621 +/- 82 vs. 247 +/- 33 microg/liter, P = 0.02; GH, 5.3 +/- 1.5 vs. 10.8 +/- 3.3 microg/liter, P = 0.02). Basal serum insulin and plasma glucose levels decreased after treatment (insulin, 54 +/- 5.9 vs. 42 +/- 5.3 pmol/liter, P = 0.001; glucose, 5.7 +/- 0.1 vs. 5.3 +/- 0.0 mmol/liter, not significant), whereas palmitate kinetics were unaltered. During the clamp, the glucose infusion rate increased after pegvisomant (3.1 +/- 0.5 vs. 4.4 +/- 0.6 mg/kg.min, P = 0.02), whereas the suppression of endogenous glucose production tended to increase (0.7 +/- 0.0 vs. 0.5 +/- 0.1 mg/kg.min, not significant). Total resting energy expenditure decreased after pegvisomant treatment (1703 +/- 109 vs. 1563 +/- 101 kcal/24 h, P = 0.03), but the rate of lipid oxidation did not change significantly. CONCLUSIONS: 1) Pegvisomant treatment for 4 wk improves peripheral and hepatic insulin sensitivity in acromegaly. 2) This is associated with a decrease in resting energy expenditure, whereas free fatty acid metabolism is unaltered. 3) The data support the important direct effects of GH on glucose metabolism and add additional benefits to pegvisomant treatment for acromegaly. PMID- 17341563 TI - Insulin gene/IDDM2 locus in Japanese type 1 diabetes: contribution of class I alleles and influence of class I subdivision in susceptibility to type 1 diabetes. AB - CONTEXT: It is suggested that insulin autoimmunity plays an important role in the development of type 1 diabetes in humans. However, the association between insulin gene (INS) region (IDDM2) and type 1 diabetes has been uncertain in Asians. OBJECTIVE: A multicenter collaboration study was conducted to clarify the role of the IDDM2 region in Japan. SUBJECTS AND METHODS: In total, 661 patients with type 1 diabetes and 706 control subjects were enrolled. The INS variable number of tandem repeat (VNTR) class I/class III status was estimated by genotyping the -23 HphI single nucleotide polymorphism. From surrounding polymorphisms across the insulin gene, we also inferred haplotypes bearing INS VNTR lineages. RESULTS: The frequency of the class I allele was 99.3% in patients and 96.7% in controls (P < 10(-5)), and the class I/III or III/III genotype was found in 1.4% of patients and in 6.4% of controls [odds ratio (OR) 0.20, P < 10( 5)]. The class I subdivision revealed IC to increase significantly in patients with type 1 diabetes (P = 0.002), whereas ID did not; the distribution of IC and ID was significantly different between patients and controls (P = 0.014). CONCLUSION: The present study certainly shows that the IDDM2 region is also a susceptibility locus in the Japanese population. Furthermore, it was revealed that IC may be more susceptible to type 1 diabetes than ID, which could be evidence that the INS VNTR itself confers susceptibility to type 1 diabetes. PMID- 17341564 TI - Single serum activin a testing to predict ectopic pregnancy. AB - CONTEXT: Ectopic pregnancy (EP) is an important cause of maternal deaths in early pregnancy because most fatal cases result from delayed diagnosis and inappropriate investigation. OBJECTIVE: We evaluated whether the measurement of activin A may be useful in the diagnosis of EP in women with unknown pregnancy location. DESIGN: The study was designed as an open observational study. SETTING: The study was set in a tertiary referral center for obstetric care. PATIENTS: Patients were women with unknown pregnancy location (n = 536) who had complaints of bleeding, pain, or cramping. INTERVENTIONS: Interventions included clinical examination; transvaginal ultrasound scan; human chorionic gonadotropin (hCG), progesterone, and activin A measurements; laparoscopy; uterine curettage; and histological examination. MAIN OUTCOME MEASURES: Main outcome measures were pregnancy outcomes and evaluation of sensitivity, specificity, and predictive values of hCG, progesterone, and activin A as diagnostic tests for the detection of EP. RESULTS: Pregnancy outcomes included 155 (28.9%) viable intrauterine pregnancies (IUP), 305 (56.9%) first-trimester spontaneous abortion (SAB), and 76 (14.2%) EP. SAB had the lowest (P < 0.0001) hCG and progesterone concentrations, significantly lower than EP (P < 0.001) and IUP (P < 0.001). In EP, levels were significantly (P < 0.001) lower than in IUP. On the contrary, activin A levels were lowest (P < 0.0001) in EP, significantly lower than in SAB (P < 0.001) and IUP (P < 0.001). IUP had significantly (P < 0.001) lower activin A levels than SAB. When evaluated by the receiver operating curve analysis, activin A at the cutoff of 0.37 ng/ml combined a sensitivity and a specificity of 100 and 99.6%, respectively, for prediction of EP. When activin A concentrations were below the cutoff, the positive predictive value for EP was 97.43%, and 0% for concentrations higher than 0.37 ng/ml. CONCLUSIONS: Activin A measurement may identify patients at risk of EP with a high sensibility and specificity. PMID- 17341565 TI - Effects of testosterone treatment on endometrial proliferation in postmenopausal women. AB - CONTEXT: Available data concerning effects of testosterone on endometrium of postmenopausal women are seriously limited. OBJECTIVE: Our aim was to compare the influence of treatment with testosterone and/or estrogen on endometrial proliferation in healthy postmenopausal women. DESIGN: This was an open, randomized clinical study with parallel comparison of the groups. SETTING: The study was conducted at a women's health clinical research unit and a research laboratory at a university hospital. PARTICIPANTS: Sixty-three women who had experienced natural menopause participated in this study. INTERVENTIONS: After random assignment, the participants were administered orally testosterone undecanoate (40 mg every second day), estradiol valerate (2 mg daily), or both for 3 months. MAIN OUTCOME MEASURES: Endometrial thickness was measured, and endometrial proliferation evaluated on the basis of histopathology and expression of Ki-67, a proliferation marker. RESULTS: Endometrial thickness was significantly increased by treatment with estrogen alone or in combination with testosterone but was unaltered by testosterone alone. Among the women receiving estrogen alone, the proportion exhibiting histopathology indicative of proliferation increased significantly to 50% (P < 0.05), there was a nonsignificant increase to 28% with the combined treatment, whereas testosterone alone had no effect at all. Expression of Ki-67 was up-regulated significantly in both glands and stroma (P < 0.05, respectively) in both estrogen treatment groups. However, the expression was significantly higher in stroma by estrogen treatment alone than after combined treatment (P < 0.05). CONCLUSIONS: The short term treatment with testosterone of postmenopausal women does not stimulate endometrial proliferation. In addition, testosterone appears to counteract endometrial proliferation induced by estrogen to a certain extent. PMID- 17341566 TI - Low dietary sodium and exogenous angiotensin II infusion decrease plasma adiponectin concentrations in healthy men. AB - CONTENT: Adiponectin has antiinflammatory and vascular protective effects and may improve insulin sensitivity. Animal data suggest a role of the renin-angiotensin aldosterone system (RAAS) in the regulation of adiponectin. OBJECTIVE: Our objective was to investigate the role of the RAAS in regulation of adiponectin in humans in vivo. To this purpose we studied the effects of physiological (change in sodium status) and pharmacological modulation of RAAS activity (angiotensin II infusion and enalapril treatment) on plasma adiponectin. DESIGN, SETTING, AND PATIENTS: Thirty-five healthy male volunteers (aged 26 +/- 9 yr) were studied after two 7-d periods: one on a low-sodium diet (LS, 50 mmol Na(+) per day) and one on a high-sodium diet (HS, 200 mmol Na(+) per day). At the end of each period, adiponectin was measured, and its response to angiotensin II infusion (0.3, 1, and 3 ng/kg.min all during 1 h) was determined. Additionally, all subjects received 1 wk treatment of enalapril 20 mg once daily (angiotensin converting enzyme inhibition) during the HS. MAIN OUTCOME MEASURE: We measured plasma adiponectin concentrations during LS and HS and in response to angiotensin II infusion. RESULTS: The suppression of the RAAS by HS elicited a significant rise in adiponectin [LS baseline, 11.9 (8.3-16.2) microg/liter; HS baseline, 14.4 (11.2-20.4) microg/liter; P < 0.05]. All doses of angiotensin II elicited a profound decrease in adiponectin during both conditions [LS 3 ng/kg.min, 7.4 (6.3 8.9) microg/liter; HS 3 ng/kg.min, 8.4 (7.3-9.9) microg/liter; both P < 0.001 vs. baseline]. Angiotensin converting enzyme inhibition induced a significant rise in adiponectin [16.6 (10.6-20.9) microg/liter, P < 0.05 vs. HS]. CONCLUSION: Physiological and pharmacological modulation of RAAS affects plasma adiponectin with lower concentrations during the high angiotensin II conditions. The therapeutic potential of RAAS blockade as a tool to correct hypoadiponectinemia should be explored further. PMID- 17341567 TI - In vitro glycoxidized low-density lipoproteins and low-density lipoproteins isolated from type 2 diabetic patients activate platelets via p38 mitogen activated protein kinase. AB - CONTEXT: Platelet hyperactivation contributes to the increased risk for atherothrombosis in type 2 diabetes and is associated with oxidative stress. Plasma low-density lipoproteins (LDLs) are exposed to both hyperglycemia and oxidative stress, and their role in platelet activation remains to be ascertained. OBJECTIVE: The aim of this study was to investigate the effects of LDLs modified by both glycation and oxidation in vitro or in vivo on platelet arachidonic acid signaling cascade. The activation of platelet p38 MAPK, the stress kinase responsible for the activation of cytosolic phospholipase A(2), and the concentration of thromboxane B(2), the stable catabolite of the proaggregatory arachidonic acid metabolite thromboxane A(2), were assessed. RESULTS: First, in vitro-glycoxidized LDLs increased the phosphorylation of platelet p38 MAPK as well as the concentration of thromboxane B(2). Second, LDLs isolated from plasma of poorly controlled type 2 diabetic patients stimulated both platelet p38 MAPK phosphorylation and thromboxane B(2) production and possessed high levels of malondialdehyde but normal alpha-tocopherol concentrations. By contrast, LDLs from sex- and age-matched healthy volunteers had no activating effects on platelets. CONCLUSIONS: Our results indicate that LDLs modified by glycoxidation may play an important contributing role in platelet hyperactivation observed in type 2 diabetes via activation of p38 MAPK. PMID- 17341568 TI - Efficacy and safety of intranasal peptide YY3-36 for weight reduction in obese adults. AB - CONTEXT: The gastrointestinal peptide hormone, peptide YY(3-36) (PYY(3-36)), is implicated to be a postprandial satiety factor. OBJECTIVE: The aim of this study is to assess the safety, tolerability, and efficacy of intranasal PYY(3-36) to induce weight loss in obese patients. DESIGN: The study was designed as a randomized, 2-wk, single-blind placebo run-in followed by a 12-wk double-blind, placebo-controlled treatment period. SETTING: The study was set within a private and institutional practice. PATIENTS: A total of 133 obese patients (body mass index, 30-43 kg/m(2); age, 18-65 yr) participated in the study. INTERVENTION: Placebo or 200- or 600-microg PYY(3-36) was administered as an intranasal spray 20 min before breakfast, lunch, and dinner in conjunction with a hypocaloric diet and exercise. MAIN OUTCOME MEASURE: Body weight was the main outcome measure. RESULTS: The number of patients completing 12 wk on the drug was 38 of 43 (88%), 31 of 44 (70%), and 12 of 46 (26%) for placebo, 200 microg three times a day (t.i.d.) and 600 microg t.i.d., respectively. In the 600 microg t.i.d. group, 27 of 46 (59%) patients discontinued due to nausea and vomiting. Among all randomized patients who took at least one drug dose and had a postbaseline measurement, the mean body weight change from baseline was -2.8, -3.7, and -1.4 kg for placebo, 200 and 600 microg, respectively. The least squares mean difference (95% confidence interval) between placebo and 200 microg was -0.9 ( 2.6, 0.7) kg (P = 0.251). A difference of 2.11 kg was sought. No meaningful inference can be drawn from the few patients who completed the study on 600 microg. CONCLUSIONS: Intranasal PYY(3-36) as administered at these intervention doses and preprandial timing is not efficacious in inducing weight loss in obese patients after 12 wk of treatment. PMID- 17341569 TI - Vitamin D status predicts physical performance and its decline in older persons. AB - CONTEXT: Vitamin D deficiency is common among older people and can cause mineralization defects, bone loss, and muscle weakness. OBJECTIVE: The aim of this study was to investigate the association of serum 25-hydroxyvitamin D (25 OHD) concentration with current physical performance and its decline over 3 yr among elderly. DESIGN: The study consisted of a cross-sectional and longitudinal design (3-yr follow-up) within the Longitudinal Aging Study Amsterdam. SETTING: An age- and sex-stratified random sample of the Dutch older population was used. OTHER PARTICIPANTS: Subjects included 1234 men and women (aged 65 yr and older) for cross-sectional analysis and 979 (79%) persons for longitudinal analysis. MAIN OUTCOME MEASURE(S): Physical performance (sum score of the walking test, chair stands, and tandem stand) and decline in physical performance were measured. RESULTS: Serum 25-OHD was associated with physical performance after adjustment for age, gender, chronic diseases, degree of urbanization, body mass index, and alcohol consumption. Compared with individuals with serum 25-OHD levels above 30 ng/ml, physical performance was poorer in participants with serum 25-OHD less than 10 ng/ml [regression coefficient (B) = -1.69; 95% confidence interval (CI) = -2.28; -1.10], and with serum 25-OHD of 10-20 ng/ml (B = -0.46; 95% CI = -0.90; -0.03). After adjustment for confounding variables, participants with 25-OHD less than 10 ng/ml and 25-OHD between 10 and 20 ng/ml had significantly higher odds ratios (OR) for 3-yr decline in physical performance (OR = 2.21; 95% CI = 1.00-4.87; and OR = 2.01; 95% CI = 1.06-3.81), compared with participants with 25-OHD of at least 30 ng/ml. The results were consistent for each individual performance test. CONCLUSIONS: Serum 25-OHD concentrations below 20 ng/ml are associated with poorer physical performance and a greater decline in physical performance in older men and women. Because almost 50% of the population had serum 25-OHD below 20 ng/ml, public health strategies should be aimed at this group. PMID- 17341570 TI - Prolonged survival in culture of preantral follicles from polycystic ovaries. AB - CONTEXT: In polycystic ovary syndrome (PCOS), an increased proportion of follicles leave the primordial (resting) pool and initiate growth. However, there is little evidence for a reduced reproductive life span (early menopause) in women with PCOS, suggesting that the dynamics of follicle growth, and of follicle loss by atresia, is altered in PCOS. OBJECTIVE: The aim of this study was to investigate the possibility that loss of preantral follicles by atresia is reduced in PCOS, leading to prolonged follicle survival. DESIGN: We compared follicle growth in normal and polycystic ovaries using cultures of small ovarian biopsies. SETTING: Tissue samples were obtained at routine laparoscopy from 12 patients with anovulatory PCOS and 16 controls and processed in an ovarian physiology laboratory. MAIN OUTCOME MEASURES: We performed morphometric analysis of follicle population in tissue fixed at time of biopsy (d 0) or after 5, 10, or 15 d in culture. Analyses included assessment of follicle and oocyte diameter, number and proportion of primordial and growing follicles, and number and proportion of atretic follicles. RESULTS: In tissue fixed on d 0, the proportion of healthy growing follicles was, as expected, greater in ovaries from PCOS patients than in normal ovaries (64 vs. 28%; P = 0.0005), but there were no differences between PCOS and normal tissue during culture. The rate of atresia throughout the period of culture in follicles was, however, significantly lower in PCOS tissue (P < 0.0001). After culture, 80% of follicles in normal ovarian tissue were atretic compared with 53% in PCOS biopsies. CONCLUSION: Follicles from polycystic ovaries demonstrate a decreased rate of atresia in culture, suggesting a mechanism for maintaining a larger follicle pool throughout reproductive life. PMID- 17341571 TI - Hormonal and psychological factors linked to the increased thermic effect of food in malnourished fasting anorexia nervosa. AB - OBJECTIVES: In patients with anorexia nervosa (AN), weight gain is lower than that expected from the energy content of the meals. Thus we investigated the thermic effect of food (TEF) in relation to subjective feelings and plasma hormone levels in a group of AN patients. METHODS: TEF, feelings (14 items), and plasma release of beta-endorphin, ACTH, cortisol, dopamine, and catecholamines were evaluated in 15 AN patients (body mass index, 13.6 +/- 1.2 kg.m(-2)) and in 15 healthy women after three gastric loads (0, 300, 700 kcal) infused by a nasogastric tube in a blind design. RESULTS: In AN, the blind loads induced an energy-dependent increase in TEF (P < 0.001), which was higher than that observed in healthy women (P < 0.001). Only in AN, a load-dependent decline in the high basal plasma level of beta-endorphin (P < 0.01), an increase in plasma ACTH (P < 0.02) after the two caloric loads, and an increase in cortisol, norepinephrine, and dopamine levels after the 700-kcal load only (P < 0.05) were noted. A calorie dependent (P < 0.001) increase in nausea, abdominal discomfort, and fear of being fat ratings and a decrease in liking to eat (P < 0.001) and body image were observed in AN patients (P < 0.05). TEF correlated with ratings on satiation, nausea, uncomfortable abdominal swelling, body image, and fear of being fat (for all, P < 0.01). CONCLUSION: In AN women, blindly infused loads induced a dose dependent increase in TEF, which correlated with the increase in plasma cortisol, ACTH, and catecholamines as in unpleasant sensations, fear of being fat, and anxiety as well as a decline in elevated basal beta-endorphin. These results could explain the difficulty for AN patients in gaining weight. PMID- 17341572 TI - Update in osteoporosis and metabolic bone disorders. AB - Considerable progress has been made in the development and testing of agents to treat osteoporosis. Most impressive are reports on new antiresorptive agents- both bisphosphonates (ibandronate and zoledronic acid) and monoclonal antibodies (MAbs) (denosumab) directed against receptor activator of nuclear factor kappaB ligand, a key molecule in the control of commitment and activation of osteoclasts. Bisphosphonates promise convenience and potency at slowing bone loss, whereas denosumab offers powerful suppression of resorption and rapid offset of action. Attention is also shifting from the osteoclast as a target for new therapies to the osteoblast and the osteocyte, with its complex network within the depths of bone. Wnt signaling through the frizzled receptor and its coreceptor, the low-density lipoprotein receptor related protein-5, appears from both molecular and in vivo evidence to be a pivotal pathway for modulating osteoblastic activity, bone formation, and bone strength. The recently identified product of the SOST gene or sclerostin has also been shown to block Wnt signaling. Sclerostin is produced by the osteocytes buried in the bone and is a new target to treat bone loss. Clinical trial reports indicate that the calcimimetic cinacalcet can effectively treat PTH hypersecretion due to primary and secondary hyperparathyroidism and parathyroid carcinoma. Lastly, it is now recognized that the matrix protein dentin matrix protein-1 enhances the release of the phosphate-regulating factor fibroblast growth factor 23 and that mutations in dentin matrix protein-1 play a causative role in a form of hypophosphatemic rickets. PMID- 17341573 TI - Calcified adrenals associated with perinatal adrenal hemorrhage and adrenal insufficiency. PMID- 17341574 TI - An optimal treatment for pediatric Graves' disease is radioiodine. AB - CONTEXT: Antithyroid medications, surgery, and radioactive iodine have been used for more than five decades for the treatment of hyperthyroidism due to Graves' disease in children, adolescents, and adults. Despite the widespread use of these different approaches, controversy still exists relative to the merits of each treatment, especially regarding the use of radioactive iodine. OBJECTIVE: The objective of the study was to address the risk and benefits of (131)I therapy, as compared with other treatment approaches. POSITION: Long-term, spontaneous remission of Graves' disease occurs in less than 30% of children. Thus, the majority of children with Graves' disease will need definitive, curative therapy. There is little evidence that use of antithyroid medications beyond 1 or 2 yr increases the likelihood of spontaneous, long-term remission. Although the use of antithyroid medications is standard practice, the use of antithyroid medications involves definite risks. When used at sufficient doses, radioactive iodine is an effective cure for Graves' disease and is associated with few acute side effects. Potential long-term adverse side effects, including thyroid cancer and genetic damage, have yet to be observed in individuals treated as children or adolescents with (131)I. CONCLUSION: Properly administered, radioactive iodine remains an ideal form of treatment for Graves' disease in the pediatric population. Because of the increased risk of thyroid cancer associated with low-dose thyroid irradiation in children, larger, rather than smaller, doses of (131)I should be given. PMID- 17341575 TI - The optimal treatment for pediatric Graves' disease is surgery. PMID- 17341576 TI - The multiple endocrine neoplasia type-1 (MEN-1) syndrome and its effect on the pancreas. PMID- 17341577 TI - Defining the role of IGF-I therapy for short children. PMID- 17341578 TI - Triple jeopardy: nocturnal hypoglycemia after exercise in the young with diabetes. PMID- 17341579 TI - Diabetes and the risk of osteonecrosis of the jaw. PMID- 17341580 TI - The SUMO protease SENP5 is required to maintain mitochondrial morphology and function. AB - Mitochondria are dynamic organelles that undergo regulated fission and fusion events that are essential to maintain metabolic stability. We previously demonstrated that the mitochondrial fission GTPase DRP1 is a substrate for SUMOylation. To further understand how SUMOylation impacts mitochondrial function, we searched for a SUMO protease that may affect mitochondrial dynamics. We demonstrate that the cytosolic pool of SENP5 catalyzes the cleavage of SUMO1 from a number of mitochondrial substrates. Overexpression of SENP5 rescues SUMO1 induced mitochondrial fragmentation that is partly due to the downregulation of DRP1. By contrast, silencing of SENP5 results in a fragmented and altered morphology. DRP1 was stably mono-SUMOylated in these cells, suggesting that SUMOylation leads to increased DRP1 mediated fission. In addition, the reduction of SENP5 levels resulted in a significant increase in the production of free radicals. Reformation of the mitochondrial tubules by expressing the dominant interfering DRP1 or by RNA silencing of endogenous DRP1 protein rescued both the morphological aberrations and the increased production of ROS induced by downregulation of SENP5. These data demonstrate the importance of SENP5 as a new regulator of SUMO1 proteolysis from mitochondrial targets, impacting mitochondrial morphology and metabolism. PMID- 17341581 TI - Interactions of DNR1 with the apoptotic machinery of Drosophila melanogaster. AB - Caspases are crucial activators of apoptosis and NF-kappaB signaling in vertebrates and invertebrates. In Drosophila, the caspase-9 counterpart Dronc is essential for most apoptotic death, whereas the caspase-8 homolog Dredd activates NF-kappaB signaling in response to gram-negative bacterial infection. The mechanics of caspase regulation are conserved and include the activities of a family of inhibitor of apoptosis (IAP) proteins. The RING-domain-bearing protein Defense repressor 1 (Dnr1), blocks ectopic Dredd-mediated induction of an NF kappaB reporter in the Drosophila S2 cell line. In this study, we present novel data indicating that Dnr1 impacts on Dronc-dependent regulation of the apoptotic program. We show that depletion of Dnr1 results in elevated Dronc protein levels, which translates to increased caspase activation and activity upon induction of apoptosis. Conversely, we demonstrate that overexpression of Dnr1 blocks apoptotic caspase activity and prevents induction of apoptosis in tissue culture assays. Furthermore, we show that Dnr1 overexpression significantly reduces Dronc protein levels and identify the domains of Dnr1 necessary for these effects. From these data, we propose that Dnr1 inhibits initiator caspases in S2 cells. PMID- 17341582 TI - Expression of a synapsin IIb site 1 phosphorylation mutant in 3T3-L1 adipocytes inhibits basal intracellular retention of Glut4. AB - Glut4 exocytosis in adipocytes uses protein machinery that is shared with other regulated secretory processes. Synapsins are phosphoproteins that regulate a ;reserve pool' of vesicles clustered behind the active zone in neurons. We found that adipocytes (primary cells and the 3T3-L1 cell line) express synapsin IIb mRNA and protein. Synapsin IIb co-localizes with Glut4 in perinuclear vesicle clusters. To test whether synapsin plays a role in Glut4 traffic, a site 1 phosphorylation mutant (S10A synapsin) was expressed in 3T3-L1 adipocytes. Interestingly, expression of S10A synapsin increased basal cell surface Glut4 almost fourfold (50% maximal insulin effect). Insulin caused a further twofold translocation of Glut4 in these cells. Expression of the N-terminus of S10A synapsin (amino acids 1-118) was sufficient to inhibit basal Glut4 retention. Neither wild-type nor S10D synapsin redistributed Glut4. S10A synapsin did not elevate surface levels of the transferrin receptor in adipocytes or Glut4 in fibroblasts. Therefore, S10A synapsin is inhibiting the specialized process of basal intracellular retention of Glut4 in adipocytes, without affecting general endocytic cycling. While mutant forms of many proteins inhibit Glut4 exocytosis in response to insulin, S10A synapsin is one of only a few that specifically inhibits Glut4 retention in basal adipocytes. These data indicate that the synapsins are important regulators of membrane traffic in many cell types. PMID- 17341583 TI - Phosphorylation of adducin by protein kinase Cdelta promotes cell motility. AB - Protein kinase Cdelta (PKCdelta) has been implicated to play a crucial role in cell proliferation, differentiation and apoptosis. In this study, we have investigated the role of PKCdelta in cell motility using Madin-Darby canine kidney cells. Overexpression of PKCdelta promoted membrane protrusions, concomitant with increased cell motility. By contrast, suppression of PKCdelta expression by RNA interference inhibited cell motility. Moreover, a fraction of PKCdelta was detected at the edge of membrane protrusions in which it colocalized with adducin, a membrane skeletal protein whose phosphorylation state is important for remodeling of the cortical actin cytoskeleton. Elevated expression of PKCdelta correlated with increased phosphorylation of adducin at Ser726 in intact cells. In vitro, PKCdelta, but not PKCalpha, directly phosphorylated the Ser726 of adducin. Finally, we demonstrated that overexpression of both adducin and PKCdelta could generate a synergistic effect on promoting cell spreading and cell migration. Our results support a positive role for PKCdelta in cell motility and strongly suggest a link between PKCdelta activity, adducin phosphorylation and cell motility. PMID- 17341584 TI - CD8 Raft localization is induced by its assembly into CD8alpha beta heterodimers, Not CD8alpha alpha homodimers. AB - The coreceptor CD8 is expressed as a CD8alphabeta heterodimer on major histocompatibility complex class I-restricted TCRalphabeta T cells, and as a CD8alphaalpha homodimer on subsets of memory T cells, intraepithelial lymphocytes, natural killer cells, and dendritic cells. Although the role of CD8alphaalpha is not well understood, it is increasingly clear that this protein is not a functional homologue of CD8alphabeta. On major histocompatibility complex class I-restricted T cells, CD8alphabeta is a more efficient TCR coreceptor than CD8alphaalpha. This property has for the mouse protein been attributed to the recruitment of CD8alphabeta into lipid rafts, which is dependent on CD8beta palmitoylation. Here, these divergent distributions of CD8alphabeta and CD8alphaalpha are demonstrated for the human CD8 proteins as well. However, although palmitoylation of both CD8alpha and CD8beta chains was detected, this modification did not contribute to raft localization. In contrast, arginines in the cytoplasmic domain are crucial for raft localization of CD8betabeta. Most strikingly, the assembly of a non-raft localized CD8beta chain with a non-raft localized CD8alpha chain resulted in raft-localized CD8alphabeta heterodimers. Using chimeric CD8 proteins, this property of the heterodimer was found to be determined by the assembly of CD8alpha and CD8beta extracellular regions. The presence of two CD8alpha extracellular regions, on the other hand, appears to preclude raft localization. Thus, heterodimer formation and raft association are intimately linked for CD8alphabeta. These results emphasize that lipid raft localization is a key feature of human CD8alphabeta that clearly distinguishes it from CD8alphaalpha. PMID- 17341585 TI - Impaired secretion of apolipoprotein E2 from macrophages. AB - Human apoE is a multifunctional and polymorphic protein synthesized and secreted by liver, brain, and tissue macrophages. Here we show that apoE isoforms and mutants expressed through lentiviral transduction display cell-specific differences in secretion efficiency. Whereas apoE3, apoE4, and a natural mutant of apoE4 (apoE-Cys(142)) were efficiently secreted from macrophages, apoE2 and a non-natural apoE mutant (apoE-Cys(112)/Cys(142)) were retained in the perinuclear region and only minimally secreted. The secretory block for apoE2 in macrophages was not affected by the ablation of LDLR (low density lipoprotein receptor), ABCA 1, or SR-BI (scavenger receptor class B type I) but was released in the absence of low density lipoprotein receptor related protein (LRP). In co immunoprecipitation experiments, an anti-apoE antibody pulled down two times more LRP in apoE2-transduced macrophages than in apoE3-expressing macrophages. Non reducing SDS-PAGE/Western blot analyses showed that macrophage apoE2 is mostly dimeric and multimeric, whereas apoE3 is predominantly monomeric. ApoE2 retention and multimer formation also occurred in human macrophages derived from the monocyte cell line THP-1. These results were specific for macrophages, as in transduced mouse primary hepatocytes: 1) ApoE2 was secreted as efficiently as apoE3 and apoE4; 2) all isoforms were exclusively in monomeric form; 3) there was no co-immunoprecipitation of apoE and LRP. A microsomal triglyceride transfer protein (MTP) inhibitor nearly deleted apoB100 secretion from hepatocytes without affecting apoE secretion. These data show that macrophages retain apoE2, a highly expressed protein carried by about 8% of the human population. Given the role of locally produced apoE in regulating cholesterol efflux, modulating inflammation, and controlling oxidative stress, this unique property of apoE2 may have important impacts on atherogenesis. PMID- 17341586 TI - Determinants of 4 alpha-phorbol sensitivity in transmembrane domains 3 and 4 of the cation channel TRPV4. AB - TRPV4, a Ca(2+)-permeable member of the vanilloid subgroup of the transient receptor potential (TRP) channels, is activated by cell swelling and moderate heat (>27 degrees C) as well as by diverse chemical compounds including synthetic 4 alpha-phorbol esters, the plant extract bisandrographolide A, and endogenous epoxyeicosatrienoic acids (EETs; 5,6-EET and 8,9-EET). Previous work identified a tyrosine residue located in the first half of putative transmembrane segment 3 (TM3) as a crucial determinant for the activation of TRPV4 by its most specific agonist 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), suggesting that 4 alpha PDD interacts with the channel through its transmembrane segments. To obtain insight in the 4 alpha-PDD-binding site and in the mechanism of ligand-dependent TRPV4 activation, we investigated the consequences of specific point mutations in TM4 on the sensitivity of the channel to different chemical and physical stimuli. Mutations of two hydrophobic residues in the central part of TM4 (Leu(584) and Trp(586)) caused a severe reduction of the sensitivity of the channel to 4 alpha PDD, bisandrographolide A, and heat, whereas responses to cell swelling, arachidonic acid, and 5,6-EET remained unaffected. In contrast, mutations of two residues in the C-terminal part of TM4 (Tyr(591) and Arg(594)) affected channel activation of TRPV4 by all stimuli, suggesting an involvement in channel gating rather than in interaction with agonists. Based on a comparison of the responses of WT and mutant TRPV4 to 4 alpha-PDD and different 4 alpha-phorbol esters, we conclude that the length of the fatty acid moiety determines the ligand binding affinity and propose a model for the interaction between 4 alpha-phorbol esters and the TM3/4 region of TRPV4. PMID- 17341587 TI - Movement discrimination after intra-articular local anaesthetic of the ankle joint. AB - BACKGROUND: The effect on clinical safety of dampening articular mechanoreceptor feedback at the ankle is unknown. Injection of the ankle joint for pain control may result in such dampening. Athletes receiving intra-articular local anaesthetic may therefore be at increased risk of sustaining ankle injuries, which are a common reason for missed sporting participation. OBJECTIVE: To determine the effect of intra-articular local anaesthetic on movement discrimination at the ankle joint. DESIGN: Prospective, randomised, double blinded, placebo-controlled, cross-over trial. SETTING: Australian Institute of Sport Medical Centre, Canberra, Australia. PATIENTS: Twenty two healthy subjects (44 ankles) aged 18-26 were recruited for the three visits of the study. INTERVENTIONS: Subjects were tested for their initial movement discrimination scores using the active movement extent discrimination apparatus (AMEDA). They then received ultrasound-guided intra-articular injections of local anaesthetic (2% lignocaine hydrochloride) or normal saline, on two separate later occasions, before further AMEDA assessment. MAIN OUTCOME MEASURES: Change in movement discrimination scores after intra-articular injection of local anaesthetic or saline. RESULTS: Movement discrimination scores were not significantly different from control ankles after injection of either local anaesthetic or saline into the ankle joint. CONCLUSIONS: The intra-articular injection of neither 2 ml lignocaine nor an equivalent amount of normal saline resulted in significant effects on movement discrimination at the ankle joint. These results suggest that injections of local anaesthetic into the ankle joint are unlikely to significantly affect proprioception and thereby increase injury risk. PMID- 17341588 TI - Comparison of nine theoretical models for estimating the mechanical power output in cycling. AB - OBJECTIVE: To assess which of the equations used to estimate mechanical power output for a wide aerobic range of exercise intensities gives the closest value to that measured with the SRM training system. METHODS: Thirty four triathletes and endurance cyclists of both sexes (mean (SD) age 24 (5) years, height 176.3 (6.6) cm, weight 69.4 (7.6) kg and Vo(2)max 61.5 (5.9) ml/kg/min) performed three incremental tests, one in the laboratory and two in the velodrome. The mean mechanical power output measured with the SRM training system in the velodrome tests corresponding to each stage of the tests was compared with the values theoretically estimated using the nine most referenced equations in literature (Whitt (Ergonomics 1971;14:419-24); Di Prampero et al (J Appl Physiol 1979;47:201 6); Whitt and Wilson (Bicycling science. Cambridge: MIT Press, 1982); Kyle (Racing with the sun. Philadelphia: Society of Automotive Engineers, 1991:43-50); Menard (First International Congress on Science and Cycling Skills, Malaga, 1992); Olds et al (J Appl Physiol 1995;78:1596-611; J Appl Physiol 1993;75:730 7); Broker (USOC Sport Science and Technology Report 1-24, 1994); Candau et al (Med Sci Sports Exerc 1999;31:1441-7)). This comparison was made using the mean squared error of prediction, the systematic error and the random error. RESULTS: The equations of Candau et al, Di Prampero et al, Olds et al (J Appl Physiol 1993;75:730-7) and Whitt gave a moderate mean squared error of prediction (12.7%, 21.6%, 13.2% and 16.5%, respectively) and a low random error (0.5%, 0.6%, 0.7% and 0.8%, respectively). CONCLUSIONS: The equations of Candau et al and Di Prampero et al give the best estimate of mechanical power output when compared with measurements obtained with the SRM training system. PMID- 17341589 TI - Comparison of three types of full-body compression garments on throwing and repeat-sprint performance in cricket players. AB - OBJECTIVE: To compare the effects of three types of full-body compression garments (Skins, Adidas and Under Armour) on repeat-sprint and throwing performance in cricket players. METHODS: Following familiarisation, 10 male cricket players performed four randomised exercise sessions (3 garments and a control). Each session involved a 30 min repeat-sprint exercise protocol comprising 20 m sprints every minute, separated by submaximal exercise. Throwing tests included a pre-exercise and a postexercise maximal distance test and accuracy throwing tests. During each session, measures of heart rate, skin temperature, change in body mass, rate of perceived exertion and perceived muscle soreness were recorded. Capillary blood samples were analysed before and after exercise for lactate, pH, O(2) saturation and O(2) partial pressure, and 24 h after exercise for creatine kinase (CK). Ratings of perceived muscle soreness were also obtained 24 h after exercise. RESULTS: No significant differences (p>0.05) were evident in repeat-sprint performance (10 m, 20 m time or total submaximal distance covered) or throwing performance (maximum distance or accuracy). No significant differences (p>0.05) were observed in heart rate, body mass change or blood measures during exercise. Significant differences (p<0.05) were observed by way of higher mean skin temperature, lower 24 h postexercise CK values and lower 24 h postexercise ratings of muscle soreness when wearing compression garments. Analysis between respective brands of compression garments revealed no statistical differences (p>0.05). CONCLUSIONS: No benefit was noted when wearing compression garments for repeat-sprint or throwing performance; however, the use of the garments as a recovery tool, when worn after exercise, may be beneficial to reduce postexercise trauma and perceived muscle soreness. PMID- 17341590 TI - Testosterone patch improves ovarian follicular response to gonadotrophins in a patient with Kallmann's syndrome: a case report. AB - Achieving ovulation in women with Kallmann's syndrome requires both exogenous FSH and LH to successfully stimulate follicular maturation and ovarian steroidogenesis. We present a case of a woman with Kallmann's syndrome, who had poor ovarian response to stimulation by exogenous gonadotrophins. When she was given testosterone by patch before initiation of gonadotrophins, her stimulation dramatically improved. Once we ceased to pretreat her cycle with testosterone, she again had a poor stimulation. This suggests that testosterone administration may be a useful adjunct in improving ovarian response to gonadotrophins in Kallmann's syndrome patients. PMID- 17341591 TI - Into the 21st century. PMID- 17341592 TI - Obituary: Bernard Theodoor Marie Tervoort: May 29, 1920,Groesbeek, the Netherlands--August 17, 2006, Bussum, the Netherlands. PMID- 17341593 TI - Ikaros is regulated through multiple histone modifications and deoxyribonucleic acid methylation in the pituitary. AB - The transcription factor Ikaros (Ik) is at the center of a functionally diverse chromatin-remodeling network that is critical for the development and regulation of both the immune and endocrine systems. Dominant negative forms of Ik result in neoplastic growth in mouse genetic studies and have been identified in human tumors. Ik modulates chromatin accessibility through associations with members of the NURD complex including histone deacetylase complexes. We show here that Ik expression in mouse pituitary corticotroph cells is itself regulated through histone modifications as well as DNA methylation. Examination of primary human pituitary specimens also identified a correlation of loss of Ik expression with the presence of DNA methylation in the untranslated exon 1 CpG island. These findings have important implications for the understanding of Ikaros' role in epigenetic functions and suggest a potential role for demethylating agents in the treatment of related disorders. PMID- 17341594 TI - An intron control region differentially regulates expression of thyroid hormone receptor beta2 in the cochlea, pituitary, and cone photoreceptors. AB - The Thrb gene, encoding thyroid hormone receptor beta (TRbeta), serves key roles in endocrine regulation and the development of the senses of hearing and color vision. The versatile functions of this gene depend upon its expression of distinct receptor isoforms by differential promoter activation. The TRbeta2 isoform has a particularly specialized distribution including in the anterior pituitary and cochlea. TRbeta2 is also found in immature cone photoreceptors where it has a unique role in programming the expression pattern of opsin photopigments that mediate color vision. Given the importance of precise, tissue specific expression for the function of TRbeta2, we investigated the genomic control elements that direct this expression in vivo using lacZ reporter transgenes in mice. The TRbeta2 promoter region is sufficient for cochlear expression, whereas a complex intron control region is necessary for pituitary and retinal expression. In the retina, the intron region directs peak expression in the embryo in postmitotic, immature cones. The retinal control region is further subdivided into domains that specify and amplify expression, respectively, indicating that timely, cone-specific expression reflects an integrated response to complex signals. The mammalian Thrb gene has therefore incorporated several mechanisms into a multifunctional intron control region that regulates developmental induction of the distant promoter. This specialized genomic organization underlies the unique expression pattern and functions of TRbeta2. PMID- 17341595 TI - Multiple roles of the nuclear receptors for oxysterols liver X receptor to maintain male fertility. AB - Oxysterol nuclear receptors liver X receptor (LXR)alpha and LXRbeta are known to regulate lipid homeostasis in cells exposed to high amounts of cholesterol and/or fatty acids. In order to elucidate the specific and redundant roles of the LXRs in the testis, we explored the reproductive phenotypes of mice deficient of LXRalpha, LXRbeta, and both, of which only the lxralpha;beta-/- mice are infertile by 5 months of age. We demonstrate that LXRalpha-deficient mice had lower levels of testicular testosterone that correlated with a higher apoptotic rate of the germ cells. LXRbeta-deficient mice showed increased lipid accumulation in the Sertoli cells and a lower proliferation rate of the germ cells. In lxralpha;beta-/- mice, fatty acid metabolism was affected through a decrease of srebp1c and increase in scd1 mRNA expression. The retinoid acid signaling pathway was also altered in lxralpha;beta-/- mice, with a higher accumulation of all-trans retinoid receptor alpha, all-trans retinoid receptor beta, and retinoic aldehyde dehydrogenase-2 mRNA. Combination of these alterations might explain the deleterious phenotype of infertility observed only in lxralpha;beta-/- mice, even though lipid homeostasis seemed to be first altered. Wild-type mice treated with a specific LXR agonist showed an increase of testosterone production involving both LXR isoforms. Altogether, these data identify new roles of each LXR, collaborating to maintain both integrity and functions of the testis. PMID- 17341596 TI - Guanosine 3',5'-cyclic monophosphate (cGMP)/cGMP-dependent protein kinase induce interleukin-6 transcription in osteoblasts. AB - Natriuretic peptides and nitric oxide (NO) activate the cGMP/cGMP-dependent protein kinase (PKG) signaling pathway and play an important role in bone development and adult bone homeostasis. The cytokine IL-6 regulates bone turnover and osteoclast and osteoblast differentiation. We found that C-type natriuretic peptide and the NO donor Deta-NONOate induced IL-6 mRNA expression in primary human osteoblasts, an effect mimicked by the membrane-permeable cGMP analog 8 chlorophenylthio-cGMP (8-CPT-cGMP). Similar results were obtained in rat UMR106 osteosarcoma cells, where C-type natriuretic peptide and 8-CPT-cGMP stimulated transcription of the human IL-6 promoter and increased IL-6 secretion into the medium. Cotransfection of type I PKG enhanced the cGMP effect on the IL-6 promoter, whereas small interfering RNA-mediated silencing of PKG I expression prevented the cGMP effect on IL-6 mRNA expression. Step-wise deletion of the IL-6 promoter demonstrated a cAMP response element to be critical for transcriptional effects of cGMP, and experiments with dominant interfering proteins showed that cGMP activation of the promoter required cAMP response element binding-related proteins, and, to a lesser extent, proteins of the CAAT enhancer-binding protein and activator protein-1 (Fos/Jun) families. 8-CPT-cGMP induced nuclear translocation of type I PKG and increased cAMP response element binding-related protein phosphorylation on Ser(133). PKG regulation of the IL-6 promoter appeared to be of physiological significance, because inhibitors of the NO/cGMP/PKG signaling pathway largely prevented fluid shear stress-induced increases of IL-6 mRNA in UMR106 cells. PMID- 17341597 TI - Oxidative upregulation of Bcl-2 in healthy lymphocytes. AB - In many cell systems, pharmacological glutathione (GSH) depletion with the GSH neosynthesis inhibitor buthionine sulfoximine (BSO) leads to cell death and highly sensitizes tumor cells to apoptosis induced by standard chemotherapeutic agents. However, some tumor cells upregulate Bcl-2 in response to BSO, thus surviving the treatment and failing to be chemosensitized. Cell lines of monocytic and lymphocytic origins respond to BSO treatment in an opposite way, lymphocytes being chemosensitized and unable to transactivate Bcl-2. In this article we investigate the response to BSO of lymphocytes freshly isolated from peripheral blood of healthy donors. After ensuring that standard separation procedures do not alter per se lymphocytes redox equilibrium nor Bcl-2 levels in the first 24 h of culture, we show that BSO treatment promotes the upregulation of Bcl-2, with a mechanism involving the increased radical production consequent to GSH depletion. Thus, BSO treatment may increase the differential cytocidal effect of cytotoxic drugs in tumor versus normal lymphocytes. PMID- 17341598 TI - Intracellular pro-oxidant activity of melatonin deprives U937 cells of reduced glutathione without affecting glutathione peroxidase activity. AB - It was long believed that melatonin might counteract intracellular oxidative stress because it was shown to potentiate antioxidant endogenous defences, and to increase the activity of many antioxidant enzymes. However, it is now becoming evident that when radicals are measured within cells, melatonin increases, rather than decreasing, radical production. Herein we demonstrate a pro-oxidant effect of melatonin in U937 cells by showing an increase of intracellular oxidative species and a depletion of glutathione (GSH). The activity of glutathione peroxidase is not modified by melatonin treatment as it does occur in other experimental models. PMID- 17341599 TI - Mitochondrial "movement" and lens optics following oxidative stress from UV-B irradiation: cultured bovine lenses and human retinal pigment epithelial cells (ARPE-19) as examples. AB - Mitochondria provide energy generated by oxidative phosphorylation and at the same time play a central role in apoptosis and aging. As a byproduct of respiration, the electron transport chain is known to be the major intracellular site for the generation of reactive oxygen species (ROS). Exposure to solar and occupational ultraviolet (UV) radiation, and thus production of ROS and subsequent cell death, has been implicated in a large spectrum of skin and ocular pathologies, including cataract. Retinal pigment epithelial cell apoptosis generates photoreceptor dysfunction and ultimately visual impairment. The purpose of this article was to characterize in vitro changes following oxidative stress with UV-B radiation in (a) ocular lens optics and cellular function in terms of mitochondrial dynamics of bovine lens epithelium and superficial cortical fiber cells and (b) human retinal pigment epithelial (ARPE-19) cells. Cultured bovine lenses and confluent cultures of ARPE-19 cells were irradiated with broadband UV B radiation at energy levels of 0.5 and 1.0 J/cm(2). Lens optical function (spherical aberration) was monitored daily up to 14 days using an automated laser scanning system that was developed at the University of Waterloo. This system consists of a single collimated scanning helium-neon laser source that projects a thin (0.05 mm) laser beam onto a plain mirror mounted at 45 degrees on a carriage assembly. This mirror reflects the laser beam directly up through the scanner table surface and through the lens under examination. A digital camera captures the actual position and slope of the laser beam at each step. When all steps have been made, the captured data for each step position is used to calculate the back vertex distance for each position and the difference in that measurement between beams. To investigate mitochondrial movement, the mitochondria-specific fluorescent dye Rhodamine 123 was used. Time series were acquired with a Zeiss 510 (configuration Meta 18) confocal laser scanning microscope equipped with an inverted Axiovert 200 M microscope and 40-x water-immersion C-Apochromat objective (NA 1.2). The optical analysis showed energy level-dependent increases in back vertex distance variability (loss of sharp focus) from 0.39 +/- 0.04 mm (control, n = 11) to 1.63 +/- 0.33 mm (1.0 J/cm(2), n = 10) and 0.63 +/- 0.13 mm (0.5 J/cm(2), n = 9). Confocal laser scanning microscopy analysis of both bovine lenses and ARPE-19 cells showed that following treatment at 0.5 J/cm(2) the mitochondria stopped moving immediately whereas at 1.0 J/cm(2) not only did the mitochondria stop moving, but fragmentation and swelling was seen. Untreated control tissue exhibited up to 15 microm/min of movement of the mitochondria. This could represent normal morphological change, presumably allowing energy transmission across the cell from regions of low to regions of high ATP demand. Lack of mitochondrial movement, fragmentation, and swelling of mitochondria may represent early morphological changes following oxidative stress that may lead to activation of caspase-mediated apoptotic pathways. PMID- 17341600 TI - 2-Methoxyestradiol inhibits superoxide anion generation while it enhances superoxide dismutase activity in swine granulosa cells. AB - 2-Methoxyestradiol (2-ME) is an estradiol metabolite with antiangiogenic properties. It can be produced by granulosa cells and it is present in normal follicle at high concentrations. The identification of reactive oxygen species (ROS) role in the molecular pharmacology of 2-ME is an active area of research. The objective of this article was therefore to evaluate the effect of 2-ME on both superoxide anion (O(2)(-)) production and superoxide dismutase (SOD) activity in swine granulosa cells collected from follicles greater than 5 mm and treated for 48 h with 1 muM 2-ME. 2-ME inhibited (P < 0.001) O(2)(-) generation in swine granulosa cells, while it stimulated (P < 0.05) the SOD activity. We previously demonstrated that a stimulation of O(2)(-) generation triggers angiogenetic response in granulosa cells. Therefore, we argue that the inhibitory effect of 2-ME on O(2)(-) could be responsible for its antiangiogenetic effect. PMID- 17341601 TI - Role of reactive oxygen species in Kv channel inhibition and vasoconstriction induced by TP receptor activation in rat pulmonary arteries. AB - Voltage-gated potassium channels (Kv) and thromboxane A(2) (TXA(2)) have been involved in several forms of human and experimental pulmonary hypertension. We have reported that the TXA(2) analog U46619, via activation of TP receptors and PKCzeta, inhibited Kv currents in rat pulmonary artery smooth muscle cells (PASMC), increased cytosolic calcium, and induced a contractile response in isolated rat and piglet pulmonary arteries (PA). Herein, we have analyzed the role of reactive oxygen species (ROS) in this signaling pathway. In rat PA, U46619 increased dichlorofluorescein fluorescence, an indicator of intracellular hydrogen peroxide, and this effect was prevented by the NADPH oxidase inhibitor apocynin and by polyethyleneglycol-catalase (PEG-catalase, a membrane-permeable form of catalase). U46619 inhibited Kv currents in native PASMC and these effects were strongly inhibited by apocynin. The contractile responses to U46619 in isolated PA were inhibited by PEG-catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin. A membrane permeable of hydrogen peroxide, t-butyl hydroperoxide, also inhibited Kv currents and induced a contractile response. Activation of NADPH oxidase and the subsequent production of hydrogen peroxide are involved in the Kv channel inhibition and the contractile response induced by TP receptor activation in rat PA. PMID- 17341602 TI - DNA strand breaks by metal-induced oxygen radicals in purified Salmonella typhimurium DNA. AB - Purified Salmonella typhimurium DNA was incubated for 1h at 37 degrees C with various concentrations (10-100 muM) of transition metal ions (Fe(2+), Fe(3+), Cu(2+), Ni(2+), Cd(2+)), with various concentrations (0.1-100 mM) of H(2)O(2), and with various concentrations of each transition metal ion in the presence of various concentrations of H(2)O(2). Damage to DNA was assessed by electrophoresis of the reaction mixtures in 1% agarose gel. Breakage of the DNA strands would produce a series of DNA fragments resulting in a smear in the gel, while intact DNA produced a single band. Results showed that no damage to the DNA was detectable after incubation with either H(2)O(2) alone or either of the metal ions alone. However, all of the metal ions investigated triggered DNA breakage in the presence of H(2)O(2). The extent of breakage depended on the metal ion and on its concentration, as well as on the H(2)O(2) concentration. Addition of either EDTA or catalase to the reaction mixture completely inhibited the DNA degradation, confirming the involvement of both the metal ion and the H(2)O(2) in the breakage of DNA strands. Production of the hydroxyl radical when H(2)O(2) and a metal ion were both present in the reaction mixture was evidenced by the thiobarbituric acid method. The most extensive damage was caused by Cu(2+) followed, in decreasing order, by Fe(2+), Fe(3+), Ni(2+), and Cd(2+). PMID- 17341603 TI - Antioxidant enzymes during hypoxia-anoxia signaling events in Crocus sativus L. corm. AB - The activity of reactive oxygen species (ROS)-scavenging enzymes, catalase, superoxide dismutase (SOD), glutathione peroxidase, o-dianisidine and ascorbate peroxidases, was investigated in Crocus sativus L. corms cultivated in normoxic and hypoxic-anoxic conditions. The activity of the ROS-scavenging enzymes studied varied during cultivation. However, the pattern of ROS-scavenging enzymes production was different in corms cultivated in normoxic and hypoxic-anoxic conditions. In normoxic conditions, only the activities of peroxidases and SOD were stimulated. In dormant corms placed under hypoxia-anoxia, the activities of catalase, SOD, and glutathione peroxidase were stimulated, with the highest stimulation observed for catalase, followed by SOD, and then glutathione peroxidase. In corms that had been rooted for 3 days before being placed in hypoxia-anoxia, the activities of all ROS-scavenging enzymes studied were stimulated with the highest stimulation still observed for catalase, followed by the peroxidases, and finally SOD. Thus catalase was the prevailing enzyme produced under hypoxia-anoxia. PMID- 17341604 TI - Ataxia-telangiectasia-mutated-dependent activation of Ku in human fibroblasts exposed to hydrogen peroxide. AB - DNA is damaged in cells during cell replication, by infection, or by various environmental stresses. The damaged cells stop cell cycle, repair damaged DNA, and when repaired progress into the next cell cycle stage. But when the attempt to repair the damage fails, the cells undergo apoptosis. The most deleterious damage of all is double-strand DNA breaks (DSBs), where ATM (ataxia telangiectasia-mutated) serves as a sensor. The ATM pathway culminates in DNA repair through nonhomologous end-joining or through homologous recombination. Upon DNA damage, the DNA repair protein Ku70/80 translocates into the nucleus, which may be mediated by ATM. Previously, we found that pancreatic acinar cells undergo apoptosis upon oxidative stress, and the cell death stems from nuclear loss of Ku70/80. This study aims to investigate whether ATM has a role in Ku activation and prevention of cell death induced by oxidative stress (hydrogen peroxide) using A-T fibroblasts stably transfected with human full-length ATM cDNA or empty vector. As a result, hydrogen peroxide-induced cell death was augmented in A-T cells transfected with empty vector while cell death was prevented in A-T fibroblasts stably transfected with human full-length ATM cDNA. Ku DNA-binding activity induced by hydrogen peroxide treatment was increased in the A-T fibroblasts stably transfected with human full-length ATM cDNA compared to that in A-T cells transfected with empty vector. The results suggest that ATM may be essential for Ku activation to repair DNA damage from oxidative stress and prevent cell death caused by oxidative stress. PMID- 17341605 TI - Regulation of 2-deoxy-D-glucose transport, lactate metabolism, and MMP-2 secretion by the hypoxia mimetic cobalt chloride in articular chondrocytes. AB - Articular cartilage is an avascular tissue with significantly reduced levels of oxygen and nutrients compared to plasma and synovial fluid. Therefore, chondrocyte survival and cartilage homeostasis require effective mechanisms for oxygen and nutrient signaling. To gain a better understanding of the mechanisms responsible for oxygen and nutrient sensing in chondrocytes, we investigated the effects of hypoxic stimulation induced by cobalt chloride treatment (a hypoxia mimetic) on glucose uptake and lactate production in chondrocytes. We also studied the effects of cobalt chloride and glucose deprivation on the expression and secretion of active MMP-2. Primary cultures of articular chondrocytes were either maintained in 20% O(2) (normoxia) or exposed to the hypoxia-mimetic cobalt chloride for up to 24 h at the following concentrations: 15 microM, 37.5 microM, and 75 microM. Glucose transport was determined by measuring the net uptake of nonmetabolizable 2-deoxy-D-[2, 6-(3)H] glucose into chondrocytes. Active MMP-2 secretion was assayed by gelatin zymography. Lactic acid production was assayed using a lactate kit. Exposure to cobalt chloride significantly increased the uptake of 2-deoxy-D-[2, 6-(3)H] glucose and the production of lactate. Glucose deprivation and cobalt chloride treatment increased levels of active MMP-2 in the culture medium. Our results suggest that these metabolic alterations are important events during adaptation to hypoxia. Upregulation of MMP-2 and the build-up of lactic acid will have detrimental effects on the extracellular matrix and may contribute to the pathogenesis and progression of osteoarthritis (OA). PMID- 17341606 TI - Oxidative stress response in telomerase-immortalized fibroblasts from a centenarian. AB - It has been reported that cells with ectopic expression of telomerase are more resistant to apoptotic cell death than their normal counterpart. However, controversial results were obtained when the cellular response to oxidative stress was analyzed. The present research was therefore aimed at defining the effect of the oxidative stress induced by tert-butylhydroperoxide (tBOOH) and 2 deoxy-D-ribose (D-ribose) in human fibroblasts from a centenarian (cen3) and, in parallel, on the same cells after telomerase immortalization (cen3tel cells). By studying different parameters of apoptosis in situ (i.e., chromatin condensation, phosphatidylserine externalization, and DNA fragmentation), we found that both tBOOH and D-ribose induce apoptosis to a greater extent in cen3 than in cen3tel cells, suggesting a protective role of telomerase toward apoptotic death. However, monitoring the cell number during treatment with the drugs, we found a decrease in cell number; since this reduction was lower in cen3 fibroblasts compared to cen3tel cells, it is likely that telomerase does not fully protect cells from drug toxicity. PMID- 17341607 TI - Differential modulation of AMPK signaling pathways by low or high levels of exogenous reactive oxygen species in colon cancer cells. AB - This study was undertaken to examine the effect of low and high concentrations of H2O2 on cancer cell proliferation and apoptosis, and AMPK signaling pathways in HT-29 human colon cancer cells. Nontoxic doses of H2O2 (10 microM) induced cancer cell proliferation, whereas the toxic level of 1,000 microM H2O2 induced apoptosis. The stimulation of cell proliferation was accompanied with an increase in cyclooxygenase-2 (COX-2), and apoptosis induced by high-dose H2O2 was correlated with the activation of AMPK and negatively correlated with COX-2 expression. These results suggest that ROS at nontoxic levels can stimulate cancer cell growth by regulating AMP-activated protein kinase (AMPK) and/or COX 2, and the abundant exogenous ROS linked to the growth inhibition through modulating AMPK signaling pathways. PMID- 17341608 TI - Alterations in salivary antioxidants, nitric oxide, and transforming growth factor-beta 1 in relation to disease activity in Crohn's disease patients. AB - It has been postulated that oxidative stress, nitric oxide (NO), and transforming growth factor beta(1) (TGF- beta(1)) have major roles in the pathophysiology of Crohn's disease (CD). The aim of this study was to determine the salivary levels of total antioxidant capacity (TAC), specific antioxidants (i.e., uric acid, albumin, transferrin, and thiol molecules), lipid peroxidation (LPO), NO, and TGF beta(1) in CD patients and control subjects and to also investigate their correlation with activity of the disease. Twenty-eight patients with confirmed diagnosis of CD were enrolled and whole saliva samples were obtained. Smokers, diabetics, those who suffered from periodontitis, and those who were consuming antioxidant supplements were excluded from the study. The Crohn's Disease Activity Index (CDAI) was used to determine the severity of the disease. Twenty healthy subjects were also recruited. In CD patients significant reductions in salivary levels of TAC (0.248 +/- 0.145 vs. 0.342 +/- 0.110 mmol/L), albumin (1.79 +/- 0.42 vs. 2.3 +/- 0.2 microg/mL), and uric acid (3.1 +/- 1.4 vs. 4.1 +/- 2.0 mg/dL) were found. TGF-beta(1) was significantly increased in CD patients compared to healthy subjects (3.02 +/- 1.54 vs. 2.36 +/- 0.52 ng/mL). A fourfold increase in NO levels (198.8 +/- 39.9 vs. 50.2 +/- 21.3 micromol/L) along with a fivefold increase in LPO concentration (0.146 +/- 0.064 vs. 0.027 +/- 0.019 micromol/L) was documented in CD patients in comparison to the control group. CDAI significantly correlated with the TAC, LPO, and the interaction between TAC and LPO (r(2) = 0.625, r(2) = 0.8, F-test's P < 0.00005). Saliva of CD patients exhibits an abnormal feature with respect to oxidative stress, NO, and TGF beta(1). TAC and LPO modify the effect of each other in determination of CD severity, which underlines the importance of oxidative stress in the pathogenesis of CD. PMID- 17341609 TI - Control of bioamine metabolism by 5-HT2B and alpha 1D autoreceptors through reactive oxygen species and tumor necrosis factor-alpha signaling in neuronal cells. AB - Homeostasis of the central nervous system relies on the proper integration of cell-signaling pathways recruited by a variety of neuronal and non-neuronal factors, with the aim of tightly controlling neurotransmitter metabolism, storage, and transport. We took advantage of the 1C11 neuroectodermal cell line, endowed with the capacity to selectively differentiate into serotonergic (1C11(5 HT)) or noradrenergic (1C11(NE)) neurons, to identify functional targets of serotonin (5-hydroxytryptamine [5-HT]) and norepinephrine (NE) autoreceptors possibly involved in the control of neuronal functions. We demonstrate that 5 HT(2B) and adreno alpha(1D) receptors are coupled to reactive oxygen species (ROS) production through NADPH oxidase activation in 1C11(5-HT) and 1C11(NE) neuronal cells, respectively. In the signaling cascade linking 5-HT(2B) receptors to NADPH oxidase, phospholipase A2-mediated arachidonic acid production is required for ROS synthesis. ROS, in turn, act as second message signals and control the activation of TACE (TNF-alpha converting enzyme), a member of a disintegrin and metalloproteinase family. 5-HT(2B) and alpha(1D) receptor stimulation triggers TACE-dependent TNF-alpha shedding in the surrounding milieu of 1C11(5-HT) and 1C11(NE) cells. In these cells, shed TNF-alpha triggers degradation of 5-HT and NE into 5-HIAA and MHPG, respectively. Finally, we observe that 5-HT(2B) and alpha(1D) receptor couplings to the NADPH oxidase-TACE cascade are strictly restricted to 1C11-derived progenies that have implemented a complete neuronal phenotype. Altogether, our data indicate that couplings of 5 HT(2B) and alpha(1D) autoreceptors to ROS and TNF-alpha signaling control neurotransmitter metabolism in 1C11-derived neuronal cells. Eventually, we might explain the origin of oxidative stress and high level of TNF-alpha in neurodegenerative diseases as a consequence of deviation of normal signaling pathways coupled to neurotransmitters. PMID- 17341610 TI - Determination of oxidative stress status and concentration of TGF-beta 1 in the blood and saliva of osteoporotic subjects. AB - Preliminary reports indicate the influence of oxidative stress and interleukins, particularly TGF-beta1, in maintenance of bone mass. This study was designed to determine any possible variations of cellular lipid peroxidation, the total antioxidant power, and concentration of TGF-beta1 in blood and saliva of osteoporotic subjects in comparison to healthy people. Blood and saliva samples of 22 osteoporotic women and 22 age-matched healthy women were collected. Samples were analyzed for thiobarbituric acid-reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing ability (total antioxidant power, TAP), and concentration of TGF-beta1. The blood and saliva TAP (mean +/- SD) of osteoporotic subjects was significantly lower than that of healthy controls (606.65 +/- 119.13 vs. 665.64 +/- 63.73 mmol/L and 560.43 +/- 84.70 vs. 612.05 +/ 81.5, respectively). Blood and saliva TBARS (mean +/- SD) of osteoporotic subjects were significantly higher than those of healthy controls (0.30 +/- 0.04 vs. 0.26 +/- 0.04 and 0.23 +/- 0.03 vs. 0.16 +/- 0.04 micromol/L, respectively). Concentrations of TGF-beta1 (mean +/- SD) in plasma and saliva of osteoporotic subjects were not different in comparison to healthy subjects. Results indicate that persons with osteoporosis have an increased oxidative stress that is not accompanied by changes in TGF-beta1 levels. Use of supplementary antioxidants in osteoporotic patients may be helpful. PMID- 17341611 TI - Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. AB - Recent evidence indicates a convergence of molecular targets for both prevention and therapy of cancer. Signal-transducer-and-activator-of-transcription-3 (STAT3), a member of a family of six different transcription factors, is closely linked with tumorigenesis. Its role in cancer is indicated by numerous avenues of evidence, including the following: STAT3 is constitutively active in tumor cells; STAT3 is activated by growth factors (e.g., EGF, TGF-alpha, IL-6, hepatocyte growth factor) and oncogenic kinases (e.g., Src); STAT3 regulates the expression of genes that mediate proliferation (e.g., c-myc and cyclin D1), suppress apoptosis (e.g., Bcl-x(L) and survivin), or promote angiogenesis (e.g, VEGF); STAT3 activation has been linked with chemoresistance and radioresistance; and chemopreventive agents have been shown to suppress STAT3 activation. Thus inhibitors of STAT3 activation have potential for both prevention and therapy of cancer. Besides small peptides and oligonucleotides, numerous small molecules have been identified as blockers of STAT3 activation, including synthetic molecules (e.g., AG 490, decoy peptides, and oligonucleotides) and plant polyphenols (e.g., curcumin, resveratrol, flavopiridol, indirubin, magnolol, piceatannol, parthenolide, EGCG, and cucurbitacin). This article discusses these aspects of STAT3 in more detail. PMID- 17341612 TI - Gene expression modulation in A549 human lung cells in response to combustion generated nano-sized particles. AB - High levels of ambient air pollution are associated in humans with aggravation of asthma and of respiratory and cardiopulmonary morbidity; long-term exposures to particulate matter (PM) have been linked to possible increases in lung cancer risk, chronic respiratory disease, and increased death rates. The Biodiagnostics Group of the DLR Institute of Aerospace Medicine develops cellular test systems capable of monitoring the biological consequences of environmental conditions on humans already on cellular and molecular level. Such bioassays rely on the receptor-reporter principle, where cell lines are transfected with plasmids carrying a reporter gene under control of environment-dependent promoters (receptor), which play a key role in regulating gene expressions in response to extracellular signals. We developed the recombinant human lung epithelial cell line A549-NF-kappaB-EGFP/Neo carrying a genetically encoded fluorescent indicator for monitoring activation of the NF-kappaB signaling pathway in living cells in response to genotoxic and cytotoxic environmental influences. With this cell line we screened several candidate human radiation-responsive genes (GADD45beta, CDKN1A) and NF-kappaB-dependent genes (IL-6, NFkappaBIA, and pNF-kappaB-EGFP) for gene expression changes by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay, using cDNA obtained from total RNA isolated at various time points after exposure to combustion generated nano-sized particle samples. PMID- 17341613 TI - Multiple levels of control of the expression of the human A beta H-J-J locus encoding aspartyl-beta-hydroxylase, junctin, and junctate. AB - The human AbetaH-J-J locus is a genomic sequence which generates three functionally distinct proteins, the enzyme aspartyl-beta-hydroxylase (AbetaH), the structural protein of sarcoplasmic reticulum junctin, and the membrane-bound calcium binding protein junctate. The first and second exons are mutually exclusive when mature mRNAs are produced. Moreover, the use of different splice donors has been shown to be involved in the generation of protein diversity by alternative splicing. As to transcriptional regulation, two promoters (P1 and P2) were identified. When the P1 and P2 promoter sequences are compared, important differences are clearly detectable. The most interesting result emerging from studies focused on the P2 promoter is that the calcium-dependent transcriptional factor MEF-2 activates the transcription of junctin, junctate, and AbetaH in excitable tissues and, to a lesser extent, in kidney. No Sp1 binding sites are present in the P2 promoter. In contrast, P1 promoter contains GC-rich sequences, which have homologies with the Sp1 consensus binding site. PMID- 17341614 TI - Activation of nuclear factor kappa B by different agents: influence of culture conditions in a cell-based assay. AB - The transcription factor nuclear factor kappaB (NF-kappaB) or other components of this pathway have been identified as possible therapeutic targets in inflammatory processes, cancer, and autoimmune diseases. In order to clarify the role of NF kappaB in epithelial cells in response to different stresses, a cell-based screening assay for activation of NF-kappaB-dependent gene transcription in human embryonic kidney cells (HEK/293) was developed. This assay allows detection of NF kappaB activation by measurement of the fluorescence of the reporter protein destabilized enhanced green fluorescent protein (d2EGFP). For characterization of the cell-based assay, activation of the pathway by several agents, for example, tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), lipopolysaccharide (LPS), camptothecin and phorbol ester (PMA), and the influence of the culture conditions on NF-kappaB activation by TNF-alpha were examined. NF kappaB was activated by TNF-alpha, IL-1beta, PMA, and camptothecin in a dose dependent manner, but not by LPS. TNF-alpha results in the strongest induction of NF-kappaB-dependent gene expression. However, this response fluctuated from 30 to 90% of the cell population showing d2EGFP expression. This variation can be explained by differences in growth duration and cell density at the time of treatment. With increasing confluence of the cells, the activation potential decreased. In a confluent cell layer, only 20-35% of the cell population showed d2EGFP expression. The underlying mechanism of this phenomenon can be the production of soluble factors by the cells inhibiting the NF-kappaB activation or direct communication via gap junctions in the cell layer diminishing the TNF alpha response. PMID- 17341615 TI - Atrial appendage transcriptional profile in patients with atrial fibrillation with structural heart diseases. AB - During the last few years DNA microarray studies of gene expression changes in human atrial tissues from patients with and without atrial fibrillation (AF) have been performed. For this purpose, tissue samples are usually collected from AF patients undergoing open heart surgery. These investigations have limitations associated with the unavoidable heterogeneity of compared groups which is due to the presence of various structural changes accompanying different sets of underlying heart diseases in both groups. It is thus reasonable to compare the atrial tissue samples from AF patients with those from individuals without signs of cardiovascular disease. To address this, we selected the atrial tissue samples from 12 AF patients (who underwent open heart surgery) and compared them with control atrial tissue samples from 10 individuals with no signs of cardiovascular diseases (those who died due to street accident). cDNA microarray method and reverse transcription-polymerase chain reaction (RT-PCR) analysis were used to identify genes which can discriminate between control and pathologically altered atrial tissues. Thirty-nine genes were found to be differentially expressed in pathologically altered tissues samples independently of the type of the underlying structural heart disease. These genes are involved in signal transduction, gene transcription regulation, cell proliferation, and apoptosis. The greatest alterations were observed for NOR1, DEC1, MSF, and Bcl2A1 genes (5 to 28-fold decrease, P < 0.05). Additional studies are needed to determine the specific role of each selected gene in pathophysiological changes leading to AF. PMID- 17341616 TI - DNA hypomethylation of CAGE promotors in squamous cell carcinoma of uterine cervix. AB - This study was performed to determine whether promotor hypomethylation of CAGE is involved in cervical carcinogenesis. The surgical specimens of 40 cervical squamous cell carcinoma patients treated at Seoul National University Hospital and those of 48 healthy controls were used, with informed consent. We investigated the promotor hypomethylation status of CAGE by methylation-specific polymerase chain reaction (MSP) using primers specific for unmethylated sequences, and found hypomethylation of CAGE promotor at a frequency approaching 90% in cervical squamous cell carcinomas (35/40, 87.5%), but at less than 4% in controls (P < 0.001). This finding provides experimental evidence of the frequent hypomethylation of normally methylated CAGE promotor CpG islands in cervical cancer, and indicates that this hypomethylation is likely to be a valuable surrogate marker for the expression of CAGE. It also provides a clue concerning the molecular mechanisms of carcinogenesis in cervical squamous cell carcinoma. PMID- 17341617 TI - The MECP2 gene mutation screening in Rett syndrome patients from Croatia. AB - Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder almost exclusively affecting females and is usually sporadic. Mutations in MECP2 gene have been found in more than 80% of females with typical features of RTT. In this study, we analyzed 15 sporadic cases of RTT. In 7 of 15 patients (47%), we detected pathogenic mutations in the coding parts of MECP2 fourth exon. We found two missense (T158M, R133C), two nonsense (R168X, R270X), two frameshift mutations (P217fs and a double deletion of 28-bp at 1132-1159 and 10-bp at 1167 1176), and one in-frame deletion (L383_E392del10). To our knowledge, the last two mutations have not been reported yet. We also detected one previously described polymorphism (S194S). In conclusion, these results show that the fourth exon should be the first one analyzed because it harbors most of the known mutations. Moreover, mutation-negative cases should be further analyzed for gross rearrangements. This is the first study of its kind in Croatia and it enabled us to give the patients an early confirmation of RTT diagnosis. PMID- 17341618 TI - Prostaglandins regulate transcription by means of prostaglandin response elements located in the promoters of mammalian Na,K-ATPase beta 1 subunit genes. AB - Prostaglandins are potent products of arachidonic acid metabolism that play significant roles in regulating ion transport in the kidney. In the Madin Darby canine kidney (MDCK) cell line prostaglandin E(1) (PGE(1)) stimulates the activity of the Na,K-ATPase and regulates transcription. Transient transfection studies conducted in MDCK cells with a human Na,K-ATPase beta1 subunit promoter/luciferase construct, pHbeta1-1141 Luc, showed a PGE(1) stimulation. The PGE(1) stimulation was inhibited by the PGE receptor antagonists SC19220 and AH6809, indicating the involvement of EP1 receptors (coupled to phospholipase C) and EP2 receptors (coupled to adenylate cyclase), respectively. A prostaglandin regulatory element (PGRE) within the beta1 subunit promoter (-110 to -92, AGTCCCTGC) is sufficient to elicit a PGE(1) stimulation in a heterologous promoter (in pLUC-MCS). Studies with promoter mutants indicated that in addition to the PGRE, an adjacent Sp1 site was also essential for regulation by PGE(1). Consistent with the involvement of Sp1 are the results of DNA affinity precipitation studies, which indicate that Sp1 as well as CREB, and Sp3 all bind to the PGRE. The involvement of this PGRE in transcriptional regulation of the Na,K-ATPase beta1 gene was examined in a number of species. Only human and chimpanzee promoters possessed an identical PGRE site, unlike dog, rat, and mouse, which possessed Sp1 sites in similar locations. Two alternative PGREs were subsequently identified. The sequence of the one of these PGREs (TGACCTTC, -445 to -438) was conserved throughout all species examined, suggesting its physiologic significance. PMID- 17341619 TI - Different modulation of ER-mediated transactivation by xenobiotic nuclear receptors depending on the estrogen response elements and estrogen target cell types. AB - Recent studies demonstrated that constitutive androstane receptor (CAR) inhibits ER-mediated transactivation of both endogenous and synthetic estrogen responsive promotor in Hep G2. Whereas steroid and xenobiotic receptor (SXR) but not peroxisome proliferator-activated receptor-gamma (PPAR-gamma) was also reported to repress estrogen receptor (ER) transactivation of the synthetic 4ERE in Hep G2, the effects of these xenobiotic nuclear receptors (XNRs) on the endogenous estrogen responsive promotor remain to be determined. Effects of CAR, SXR, and PPAR-gamma on ER transactivation were also examined in three different kinds of breast cancer cell lines. However, except in MCF-7, studies were limited either in single dose response (MDA-MB-231) or with CAR only (MCF-7-K3). And there is presently no report on the effects of CAR, SXR, and PPAR-gamma on ER-mediated transactivation in ovarian-derived CHO-S cells. Accordingly, this article further examined the effects of the endogenous vitellogenin B1 estrogen responsive promotor on the SXR- and PPAR-gamma-modulated ER transactivation in Hep G2, and either dose-dependent or single dose effects of SXR, PPAR-gamma, and CAR in two different breast cancer cell lines and the ovarian-derived cell line respectively, on the ER-mediated transactivation of the synthetic (4ERE)-tk luciferase reporter. Consistent with the previous report, CAR significantly repressed ER-mediated transactivation of the endogenous vitellogenin B1 promotor in Hep G2 cells. However, contrary to the effects on the synthetic promotor, PPAR gamma potentiated whereas SXR did not have any effects on the ER transactivation of the vitellogenin promotor in Hep G2. In the breast cancer cell line of MDA-MB 231 in which endogenous ER is known not to be expressed, CAR modestly stimulated ER transactivation of the synthetic 4ERE in a low dose whereas both SXR and PPAR gamma did not have any effects in all doses examined (20-500 ng). And in both CHO S and estrogen-independent breast cancer cell line, MCF-7-K3, none of the three xenobiotic receptors significantly influenced the ER-mediated 4ERE transactivation in all doses examined. XNRs modulate ER-mediated transactivation depending on the estrogen response elements (EREs) and estrogen target cell types. PMID- 17341620 TI - Effects of TK promotor and hepatocyte nuclear factor-4 in CAR-mediated transcriptional activity of phenobarbital responsive unit of CYP2B gene in monkey kidney epithelial-derived cell line COS-7. AB - Previous studies reported that constitutive androstane receptor (CAR) does not transactivate phenobarbital responsive unit (PBRU)2C1luciferase reporter gene in COS cells in which endogenous CYP2B1 gene is not induced with PB. In order to understand molecular mechanism(s) whereby PBRU is transactivated, this article determined if the use of strong thymidine kinase (TK) promotor rather than the minimal CYP2C1 promotor, and hepatocyte nuclear factor-4 (HNF-4) can affect CAR mediated transactivation of PBRU in the monkey kidney epithelial-derived COS-7 cells. To examine CAR-mediated transactivation, cultured COS-7 cells were transfected with CAR expression plasmid, pEGFP-mCAR1, and confirmed for high level of the protein expression. In COS-7 cells, TK promotor induced CAR-mediated PBRU transactivation in a dose-dependent manner. Whereas expression of HNF-4 slightly promoted PBRU transactivation with low amount of CAR transfected, it repressed PBRU transactivation in a dose-dependent manner with high amount of CAR. Consistent with the previous reports in Hep G2 cells, CAR transactivated PBRU2C1luciferase in a dose-dependent manner and this CAR-mediated transactivation required functional NR-1 and NF-1 sites. However, HNF-4 did not affect CAR-mediated PBRU transactivation in Hep G2 cells. These results suggest that proximal promotor and a trans-acting factor, HNF-4, can affect CAR-mediated transactivation of PBRU in COS-7 cells. PMID- 17341621 TI - Expression of the E2F family of transcription factors and its clinical relevance in ovarian cancer. AB - The E2F family of transcription factors plays a pivotal role in the regulation of cellular proliferation. On the basis of sequence homology and function, eight distinct members of E2F transcription factors (E2F-1 to E2F-8) have been distinguished to date. The regulation of E2F transcription factors is closely associated with the function of the retinoblastoma family of tumor suppressors (RB pathway). In the last decade various alterations of distinct components of the RB-E2F pathway were found to be associated with tumor progression. However, no data on the role of E2F family members are available in tumor biology of ovarian cancer. Here we describe an expression study of E2F transcription factors in various human ovarian cancer cell lines; its clinical relevance was examined in a training set of 77 ovarian cancer patients. Expression levels of E2F-1, E2F 2, and E2F-8 were elevated in all the ovarian cancer cell lines studied when compared with human peritoneal mesothelial cells (HPMCs). Interestingly, EGF treatment showed a time-dependent upregulation of the activating transcription factor E2F-3 and a simultaneous increase of DP-1, the heterodimeric partner of E2F-3. High expression of E2F-1, E2F-2, and E2F-8 was found to be associated with histopathologic grade 3 tumors and residual tumor over 2 cm in diameter after primary debulking surgery in ovarian cancer patients. Taken together, these data suggest that the proliferation-promoting E2F transcription factors E2F-1 and especially E2F-2 play a pivotal role in tumor biology of ovarian cancer and may be candidates for specific therapeutic targets. PMID- 17341622 TI - Isolation and characterization of the rat SND p102 gene promoter: putative role for nuclear factor-Y in regulation of transcription. AB - In this work, we report the isolation and characterization of a 1,688-bp sequence corresponding to the promoter region of the rat endoplasmic reticulum (ER) cholesterol ester hydrolase gene, renamed as staphylococcal nuclease domain containing protein of 102 kDa (SND p102) in GenBank database according to the structural properties and molecular weight of the protein. The transcription start site was located 216 bases upstream of the ATG start codon by RNA ligase mediated-rapid amplification of cDNA ends (RLM-RACE). Bioinformatic analysis of the isolated sequence revealed a lack of typical promoter TATA box and the presence of GC-rich motifs and CCAAT boxes recognized by Sp 1 and nuclear factor Y among other putative binding sites for a number of transcription factors implicated in both basal and regulated processes. Electrophoretic mobility shift and supershift assays using nuclear extracts from human (HepG2) and rat (McA RH7777) hepatoma cells demonstrated that nuclear factor-Y (NF-Y) transcription factor bound to the core sequences at (-257, -253), (-290, -286), and (-370, 366) upstream translation initiation site. The absence of TATA box and the location and reverse orientation of the CCAAT boxes in the promoter region strongly suggest a role for NF-Y in the regulation of transcription of SND p102 gene. PMID- 17341623 TI - The cAMP-responsive unit of the human insulin-like growth factor-binding protein 1 coinstitutes a functional insulin-response element. AB - Insulin-like growth factor-binding protein-1 (IGFBP-1) is one of the genes involved in glucose homeostasis. In vivo, its level is increased by counter regulatory hormones (glucocorticoids and glucagon via its second messenger cAMP) and decreased by insulin, these variations being primarily correlated with IGFBP 1 gene transcription. Previous reports described a functional insulin response element (IRE), immediately 5'- to the glucocorticoid response element (GRE). This IRE has been shown to mediate partial inhibition (1) of basal IGFBP-1 promoter activity and (2) of glucocorticoid-induced stimulation of gene transcription by insulin. In this work, using human HepG2 hepatoma cells as a model system, we showed: (1) that insulin inhibited both basal and cAMP-induced hIGFBP-1 promoter (nt-1 to -341) activity; (2) that in the absence of insulin, forkhead box class O (FOXO) transcription factors enhance constitutive hIGFBP-1 promoter activity without interfering with the stimulatory effect of cAMP; (3) that PI-3' kinase signaling is involved in the inhibition of constitutive and cAMP-induced promoter activities by insulin; (4) that wild-type FOXO-1 mediates the inhibitory effect of insulin on the promoter, although FOXO-1(Ala3), a nonphosphorylatable mutant of FOXO-1, does not; (5) that the cAMP-responsive unit (CRU), that includes a putative IRE (nt-265 to -282) and a cAMP responsive element (CRE; nt-258 to 263), is sufficient per se to mediate both cAMP stimulation of a heterologous promoter, and inhibition of both basal and cAMP-induced promoter activities by insulin; and (6) that the inhibitory effects of insulin on the isolated CRU are mediated by the FOXOs. This study is the first evidence for the occurrence of a second IRE within hIGFBP-1 promoter sequences, IRE(CRU), located 5'- to the CRE. PMID- 17341624 TI - c-Jun and JunB are essential for hypoglycemia-mediated VEGF induction. AB - Physiological conditions like hypoxia or hypoglycemia trigger expression of VEGF, a key regulator of angiogenesis. To elucidate the molecular mechanism underlying the VEGF regulation of hypoglycemia, we investigated the role of AP-1 transcription factor subunits c-Jun and JunB. Using c-jun(-/-) and junB(-/-) mouse embryonic fibroblasts, we demonstrate that both c-Jun and JunB are required for the hypoglycemia-mediated induction of VEGF expression. This process is independent of the master regulator of hypoxic stress HIF-1, as HIF expression and stabilization are not affected by the loss of AP-1 subunits. Analysis of signaling cascades regulating c-Jun and/or JunB activity and/or transcription upon hypoglycemia by application of specific inhibitors of protein kinase C (PKC) or extracellular signal-regulated kinase (ERK) signaling revealed that hypoglycemia-mediated induction of c-Jun is regulated via a PKCalpha-dependent signaling pathway. In contrast, JunB is activated by the MAP kinase ERK for the AP-1 subunits c-Jun and JunB to mediate VEGF regulaltion of hypoglycemia. PMID- 17341625 TI - Altered gene expression pattern in peripheral blood leukocytes from patients with arterial hypertension. AB - The role of various inflammatory mechanisms and oxidative stress in the development of atherosclerosis and arterial hypertension (AH) has been increasingly acknowledged during recent years. Hypertension per se or factors that cause hypertension along with other complications lead to infiltration of activated leukocytes in the vascular wall, where these cells contribute to the development of vascular injury by releasing cytokines, oxygen radicals, and other toxic mediators. However, molecular mechanisms underlying leukocyte activation at transcriptional level in AH are still far from being clear. To solve this problem we employed cDNA microarray technology to reveal the differences in gene expression in peripheral blood leukocytes from patients with AH compared with healthy individuals. The microarray data were verified by a semi-quantitative RT PCR method. We found 25 genes with differential expression in leukocytes from AH patients among which 21 genes were upregulated and 4 genes were downregulated. These genes are implicated in apoptosis (CASP2, CASP4, and CASP8, p53, UBID4, NAT1, and Fte-1), inflammatory response (CAGC, CXCR4, and CX3CR1), control of MAP kinase function (PYST1, PAC1, RAF1, and RAFB1), vesicular trafficking of molecules among cellular organelles (GDI-1 and GDI-2), cell redox homeostasis (GLRX), cellular stress (HSPA8 and HSP40), and other processes. Gene expression pattern of the majority of genes was similar in AH patients independent of the disease stage and used hypotensive therapy, but was clearly different from that of normotensive subjects. PMID- 17341626 TI - Effects of AT1 receptor-mediated endocytosis of extracellular Ang II on activation of nuclear factor-kappa B in proximal tubule cells. AB - Angiotensin II (Ang II) exerts powerful proinflammatory and growth effects on the development of Ang II-induced hypertensive glomerulosclerosis and tubulo interstitial fibrosis. The proinflammatory and growth actions of Ang II are primarily mediated by activation of cell surface type 1 receptors (AT(1)) and the transcription factor nuclear factor-kappaB (NF-kappaB). However, binding of cell surface receptors by extracellular Ang II also induces receptor-mediated endocytosis of the agonist-receptor complex in renal cells. The purpose of the present study was to determine whether AT(1) receptor-mediated endocytosis of extracellular Ang II is required for Ang II-induced NF-kappaB activation and subsequent proliferation of rabbit renal proximal tubule cells. Expression of AT(1) (primarily AT(1a) or human AT(1)) receptors in these cells was confirmed by Western blot, showing that transfection of a human AT(1) receptor-specific 20-25 nucleotide siRNA knocked down more than 70% of AT(1) receptor protein (P < 0.01). Stimulation of proximal tubule cells by Ang II (1 nM) induced fourfold increases in NF-kappaB activity (P < 0.01). The Ang II-increased NF-kappaB activity was significantly attenuated by coadministration of losartan (10 microM), an AT(1) receptor-selective blocker, or colchicine (1 microM), a selective cytoskeleton microtubule inhibitor known to block receptor-mediated endocytosis (P < 0.01). Furthermore, Ang II significantly increased (3)H-thymidine incorporation (>55%, P < 0.01), an index of cell proliferation and DNA synthesis, and the effect was also attenuated by coadministration of losartan and colchicine (P < 0.01). Our results therefore suggest that AT(1) receptor-mediated endocytosis of extracellular Ang II may be required for Ang II-induced NF-kappaB activation and subsequent cell proliferation in renal proximal tubule cells. PMID- 17341627 TI - Retinoic acid and histone deacetylase inhibitor BML-210 inhibit proliferation of human cervical cancer HeLa cells. AB - Human papillomavirus (HPV) infection is believed to be the central cause of cervical cancer. The viral proteins E6 and E7 from high-risk HPV types prevent cells from differentiating apoptosis and inducing hyperproliferative lesions. Human cervical carcinoma HeLa cells contain integrated human papillomavirus type 18 (HPV-18). Retinoic acid (RA) is a key regulator of epithelial cell differentiation and a growth inhibitor in vitro of HeLa cervical carcinoma cells. Cellular responses to RA are mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors. On the other hand, histone deacetylase inhibitors have been shown to be chemopreventive agents for the treatment of cancer cells. In this article, we have examined the antiproliferative effect of RA and histone deacetylase inhibitor BML-210 on HeLa cells, and particularly the effects on protein expression that may be involved in the cell cycle control and apoptosis. Our data suggest that a combination of RA and BML-210 leads to cell growth inhibition with subsequent apoptosis in a treatment time-dependent manner. We confirm that BML-210 alone or in combination with RA causes a marked increase in the level of p21. The changes in the p53 level are under the influence of p38 phosphorylation. We also discovered that the histone deacetylase inhibitor BML 210 causes increased levels of anti-apoptotic protein Bcl-2 and phosphorylated p38 MAP Kinase; the latter link in cell cycle arrest with response to extracellular stimuli. Our results suggest that RA and BML-210 are involved in different signaling pathways that regulate cell cycle arrest and lead to apoptosis of HeLa cells. PMID- 17341628 TI - Effects of histone deacetylase inhibitors, sodium phenyl butyrate and vitamin B3, in combination with retinoic acid on granulocytic differentiation of human promyelocytic leukemia HL-60 cells. AB - Water-soluble vitamin B3, niacin, and its related compounds were suggested to be applicable for medical use. In this article, we examined the anti-leukemic effects of two distinct histone deacetylase (HDAC1 and Sir2) inhibitors, sodium phenyl butyrate (PB) and vitamin B3, respectively, on human promyelocytic leukemia cells HL-60, using HDACIs alone and in combination with all trans retinoic acid (RA). We demonstrated that the HDACI combinations exert different effects on cell cycle arrest and differentiation as determined by nitro blue reduction and the expression of the early myeloid differentiation marker CD11b. The most beneficial effects were found by use of 6-h pretreatment with PB and vitamin B3 before the exposition to RA alone or in combination with vitamin B3, showing significant acceleration and a high level of granulocytic differentiation. The effects were associated with a rapid histone H4 acetylation and later histone H3 modifications. Our results suggest that the use of two HDACI altogether before the induction of differentiation and acting via chromatin remodeling may be promising for the treatment of acute promyelocytic leukemia. PMID- 17341629 TI - The histone deacetylase inhibitor FK228 distinctly sensitizes the human leukemia cells to retinoic acid-induced differentiation. AB - FK228 (depsipeptide) is a novel histone deacetylase inhibitor (HDACI) that has shown therapeutical efficacy in clinical trials for malignant lymphoma. In this article, we examined in vitro effects of FK228 on human leukemia cell lines, NB4 and HL-60. FK228 alone (0.2-1 ng/mL) inhibited leukemia cell growth in a dose dependent manner and induced death by apoptosis. FK228 had selective differentiating effects on two cell lines when used for 6 h before induction of granulocytic differentiation by retinoic acid (RA) or in combination with RA. These effects were accompanied by a time- and dose-dependent histone H4 hyper acetylation or histone H3 dephosphorylation and alterations in DNA binding of NF kappaB in association with cell death and differentiation. Pifithrin-alpha (PFT), an inhibitor of p53 transcriptional activity, protected only NB4 cells with functional p53 from FK228-induced apoptosis and did not interfere with antiproliferative activity in p53-negative HL-60 cells. In NB4 cells, PFT inhibited p53 binding to the p21 (Waf1/Cip1) promotor and induced DNA binding of NF-kappaB leading to enhanced cell survival. Thus, beneficial effects of FK228 on human promyelocytic leukemia may be exerted through the induction of differentiation or apoptosis via histone modification and selective involvement of transcription factors, such as NF-kappaB and p53. PMID- 17341630 TI - Effect of valproic acid, a histone deacetylase inhibitor, on cell death and molecular changes caused by low-dose irradiation. AB - Valproic acid (VA), a histone deacetylase inhibitor (HDACI), in vitro induces differentiation of promyelocyte leukemia cell (HL-60) and proliferation arrest and apoptosis of various leukemia cell lines. In MOLT-4 cells (human T lymphocyte leukemia) the cell cycle arrest is caused by 2 mM VA, while 4 mM VA induces mainly apoptosis. In our work we studied effect of VA on molecular mechanisms responsible for cell cycle arrest (2 mM VA) or apoptosis induction (4 mM VA). The aim of our article was to evaluate a cotreatment by low (cytostatic) concentrations of VA with ionizing radiation and an effect of this combination on apoptosis induction in tumor cells MOLT-4. We prove that 24-h long incubation with VA causes acetylation of histones H3 and H4 in concentration-dependent manners. During first hours after the beginning of cultivation with VA in both studied concentrations (2 and 4 mM) an increase of p53 and its phosphorylation on serine 392 is detected, as well as a phosphorylation of Mdm2 on serine 166. After 8 and 24 h after the beginning of cultivation with 2 mM VA we detect p21, which is not observed after exposure to 4 mM VA. Cleavage of lamin B to 46 kDa fragment as an indicator of apoptosis was apparent after 24-h long incubation with 4 mM VA. In this article we prove radiosensitizing effect of VA. After 3-days long cultivation of cells with 2 mM VA the D(0) value decreased from 0.7 to 0.2 Gy. Also the EC70 value fell from 0.97 to 0.38 mM when the cells were irradiated with a dose of 1 Gy before the continual cultivation with VA. Continual cultivation of MOLT-4 cells irradiated by the dose of 1 Gy with VA caused during 14 days after irradiation significant increase of apoptotic cells in comparison to the cells exposed to only one factor. As a conclusion it can be postulated that continual exposure of MOLT-4 cells to VA increases apoptosis and decreases colony-forming capacity of the cells irradiated with small dose of radiation. PMID- 17341631 TI - Protein folding information in nucleic acids which is not present in the genetic code. AB - Nucleic acid subsequences comprising the 1st and/or 3rd codon residues in mRNAs express significantly higher free folding energy (FFE) than the subsequence containing only the 2nd residues (P < 0.0001, n = 81). This periodic FFE difference is not present in introns. The FFE in the 1st and 3rd residues is additive, which suggests that these residues contain a significant number of complementary bases and contribute to selection for local mRNA secondary structures. This periodic, codon-related structure forming of mRNAs indicates a connection between the structure of exons and the corresponding (translated) proteins. The folding energy dot plots of RNAs and the residue contact maps of the coded proteins are indeed similar. Residue contact statistics using 81 different protein structures confirmed that amino acids that are coded by partially reverse and complementary codons (Watson-Crick base pairs at the 1st and 3rd codon positions and translated in reverse orientation) are preferentially co-located in protein structures. PMID- 17341632 TI - Antigens and cytokine genes in antitumor vaccines: the importance of the temporal delivery sequence in antitumor signals. AB - Studies against cancer, including clinical trials, have shown that a correct activation of the immune system can lead to tumor rejection whereas incorrect signaling results in no positive effects or even anergy. We have worked assuming that two signals, GM-CSF (granulocyte and macrophage colony-stimulating factor) and tumor antigens are necessary to mediate an antitumor effective response. To study which is the ideal temporal sequence for their administration, we have used a murine model of antimelanoma vaccine employing whole B16 tumor cells or their membrane protein antigens (TMPs) in combination with gm-csf transfer before or after the antigen delivery. Our results show that: (i) When gm-csf tisular transfection is performed before TMP delivery, a tumor growth inhibition is observed, but with a limit effect when administering high antigen doses; in contrast, when signals are inverted, the limited effect is lost and greater antitumor efficacy is obtained. (ii) A similar behavior, but with stronger positive results, is observed employing gm-csf transfection and whole tumor cells as antigens. While negative results are obtained with gm-csf before cells, the best results (total survival of treated mice) are obtained when GM-CSF is administered in transfected cells. We conclude that optimal antitumoral response can be obtained when the antigen signal is given before (or simultaneous with) GM CSF production, while the inversion of the signals could result in the undesired inhibition or anergy of the immune response. PMID- 17341633 TI - Arrest of cancer cell proliferation by dsRNAs. AB - Inhibition of c-myc and N-myc genes by dsRNAs in carcinoma and neuroblastoma cells was investigated. siRNA-Ex3 targeted to the third exon of c-myc gene was found to decrease the level of c-myc but not N-myc mRNA and decrease the rate or even arrest proliferation of c-myc overexpressing cell lines KB-3-1 and SK-N-MC. This siRNA did not affect proliferation of IMR-32 (which overexpress N-myc). siRNA-Ex2 corresponding (with 1-2 mismatches) to the conservative region of the second exon of both c- and N-myc was able to downregulate both genes and to reduce proliferation of KB-3-1, SK-N-MC, and IMR-32 cells. Long dsRNA corresponding to the 3 exon of c-myc gene (dsMyc), poly(I:C), and GU-rich siRNA I, corresponding to the intron sequence of human MDR1 gene demonstrated high antiproliferative activity in experiments with KB-3-1 cells. Short-term elevation of PKR or/and OAS1 mRNA levels was detected in the cells affected by interferon inducer poly(I:C). dsMyc, poly(I:C), and even siRNA-I, which could not affect c myc mRNA by RNA interference mechanism, were found to inhibit proliferation of the KB-3-1 cells and to decrease the mRNA level of interferon-sensitive genes c myc and beta-actin. PMID- 17341634 TI - Design and functional activity of phosphopeptides with potential immunomodulating capacity, based on the sequence of Grb2-associated binder 1. AB - A cell membrane permeable phosphopeptide corresponding to the SHP-2 binding motif of Grb2-associated binder 1 (Gab1) interferes with the Gab1 adaptor-dependent functions and modulates B cell receptor-triggered intracellular signaling in B cell tumors. PMID- 17341635 TI - Distinct activity of peptide mimetic intracellular ligands (pepducins) for proteinase-activated receptor-1 in multiple cells/tissues. AB - Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, can be activated not only by PAR1-activating peptides (PAR1APs) based on the N-terminal cryptic tethered ligand sequence but also by an N-palmitoylated (Pal) peptide, Pal-RCLSSSAVANRSKKSRALF-amide (P1pal-19), based on the intracellular loop 3 of PAR1, designated pepducin, in human platelets or PAR1 transfected cells. The present article evaluated the actions of P1pal-19 and also the shorter peptide, Pal-RCLSSSAVANRS-amide (P1pal-12), known as a possible PAR1 antagonist, in multiple cells/tissues that naturally express PAR1. P1pal-19 as well as a PAR1AP, TFLLR-amide, evoked cytosolic Ca(2+) mobilization in cultured human lung epithelial cells (A549) and rat gastric mucosal epithelial cells (RGM1). P1pal-19 and TFLLR-amide, but not a PAR2-activating peptide, SLIGRL amide, caused delayed prostaglandin E(2) formation in RGM1 cells. P1pal-19, like TFLLR-amide, produced endothelial NO-dependent relaxation in rat aorta and epithelial prostanoid-dependent relaxation in mouse bronchus. The P1pal-19 induced relaxation remained constant even after desensitization of PAR1 with TFLLR-amide in either tissue. P1pal-19 failed to mimic the contractile effects of TFLLR-amide in the endothelium-denuded preparations of rat aorta or superior mesenteric artery and the rat gastric longitudinal smooth muscle strips. P1pal-12 partially inhibited the vasorelaxation caused by TFLLR-amide and P1pal-19, but not SLIGRL-amide, in the rat aorta. Our data thus indicate that P1pal-19 is capable of mimicking the effects of PAR1APs in the endothelial and epithelial, but not smooth muscle, cells/tissues, and suggest that P1pal-12 may act as a PAR1 antagonist in the vascular endothelium. PMID- 17341636 TI - A new method to assess drug sensitivity on breast tumor acute slices preparation. AB - A method for assessing tumor drug sensitivity is described that is based on preparation of tissue slices and use of silicon chips equipped with electrochemical sensors (multisensor array). The tumor slices (200-300 microM thick) are prepared after surgery and incubated in a medium for recovery after slicing. The advantage, compared to other preparations, is that the original three-dimensional structure is retained. Multisensor arrays measure: (a) pericellular acidification (anaerobic metabolism) and (b) oxygen consumption (respiration). The innovative aspect is that such measurements can be made online, as opposed to using a large battery of endpoint tests on cell vitality and proliferation. Electron microscopy of slices serves to determine cell density and structure and induction of apoptosis/necrosis. Slices of more than 200 breast tumors were used. Metabolic activity was inhibited by sodium fluoride, which reduces glycolysis, and potassium cyanide, which inhibits respiration. These changes are thus reflected in the curves of acidification and oxygen consumption. In other experiments the cytostatic Taxol, an anticytoskeletal agent, was used showing dose and time-dependent effects on acidification and oxygen consumption. In conclusion, the method presented here, is able to provide information on drug sensitivity of a tumor, which aids in designing individualized therapy and is used for drug screening. PMID- 17341637 TI - Process simulation in a mechatronic bioreactor device with speed-regulated motors for growing of three-dimensional cell cultures. AB - Tissue engineering is a new scientific research field that allows the establishment of tissue equivalents rising from isolated cells in combination with biocompatible materials and cultivation in more or less sophisticated bioreactor systems. Such systems gave the unique opportunity to perform in vitro investigations of transcription and translation, cell growth, biochemistry and mechanics of healthy normal organs as well as those affected by malignant tumors, infections, and immune deficiency under controlled conditions. In rotating vessel bioreactors under microgravity and defined medium content, cells proliferate, stay abundant to each other, and form three-dimensional structures, assigned as spheroids. Such spheroids might be grown on microcarriers. A wide spectrum of different cell culture experiments involving normal and transformed human cells indicates that: in the rotating bioreactor system miniPERM no complete lack of gravity could be reached; a great part of the seeded cell material does not proliferate at the beginning; and the appearance of bigger spheroids is rather random. We describe the acquisition of spheroids from HD-MY-Z and Neuro-2A tumor cells. Spheroids of 100 and more cells were obtained from HD-MY-Z and Neuro-2A cells. Interestingly, chronic myeloid leukemia LAMA-84 cells did not form any cell clumps and they kept a completely undifferentiated phenotype despite their semiadherent manner of growth under conventional conditions. A detailed theoretical and virtual simulation study of the influence of every component of gravitation, inertia, and hydrodynamic force fields was performed. Therefore, a new concept for mechatronic bioreactor device with active electronic control was developed and virtually tested. PMID- 17341638 TI - Animal model of drug-resistant tumor progression. AB - Experimental animal model of tumor progression based on mice lymphosarcoma (LS) and resistant lymphosarcoma (RLS) has been developed. LS tumor displays high sensitivity to cyclophosphamide, which is widely used in anticancer therapy. RLS tumor was derived from LS by passaging in mice receiving low concentration of cyclophosphamide (20 mg/kg) and display resistance to cyclophosphamide (up to dose 150 mg/kg). The primary cultures of LS and RLS tumors display different expression levels of the genes related to apoptosis and multiple drug-resistant phenotype: in RLS tumor high levels of mdr1b and bcl-2 genes and low level of p53 gene expression were found. A total of 10% of cells in RLS primary culture display multiple drug-resistant phenotype and survive even at high dose of cytostatics. Cultivation of RLS primary culture in the presence of increasing vinblastine concentrations gives RLS(40) cell culture, which exhibits high levels of mdr1a/1b genes expression as compared to RLS and 20-fold increase of resistance to cytostatics. Drug-resistant RLS(40) cells were transplanted into CBA mice and sensitivity of the tumors to anticancer drugs was tested. RLS(40) tumors were resistant to a number of cytostatics used in anticancer therapy (cyclophosphamide, cysplatin, vinblastine, rubomycinum). Thus, RLS(40) tumor can be used as model, which corresponds to tumor status observed in patients after one or several courses of chemotherapy and can be useful for testing conventional therapy alone or together with newly developed gene-targeted therapeutics. PMID- 17341639 TI - Preparation and characterization of recombinant chicken growth hormone (chGH) and its putative antagonist chGH G119R mutein. AB - Synthetic cDNA of chicken GH (chGH) and its G119R mutein was synthesized after being optimized for expression in E. coli. The respective cDNAs were inserted into expression vector, expressed and found almost entirely in the insoluble inclusion bodies (IBs). The IBs were isolated, the proteins solubilized in 4.5 M urea, at pH 11.3 in presence of cysteine, refolded, and purified to homogeneity by anion-exchange chromatography on Q-Sepharose. The overall yields were 400 to 500 mg from 5 L of fermentation. Both proteins were > 98% pure, as evidenced by SDS-PAGE, and contained at least 95% monomers, as documented by gel-filtration chromatography under non-denaturing conditions. Circular dichroism analysis revealed that both proteins have identical secondary structure characteristic of cytokines, namely > 50% of alpha helix content. Chicken GH was capable of forming a 1:2 complex with recombinant oGH receptor extracellular domain, but its affinity, as determined by RRA, was 11-fold lower than that of ovine GH (oGH). Correspondingly, its bioactivity, assessed using FDC-P1 3B9 cells stably transfected with rabbit GHR, was 30-40-fold lower, whereas chGH G119R mutant did not bind to oGHR-ECD and was devoid of any biological activity in FDC-P1 3B9 cells. However, in binding experiments that were carried out using chicken liver membranes, both oGH and chGH showed similar IC(50) values in competition with (125)I-oGH, while the IC(50) of G119R mutein was 10-fold higher. These results emphasize the importance of species specificity and indicate the possibility of antagonistic activity of chGH G119R. PMID- 17341640 TI - Induction of apoptosis of osteoclasts by targeting transcription factors with decoy molecules. AB - We review the effects of two transcription factor decoy oligonucleotides on apoptosis of human osteoclasts (OCs). The first decoy molecule was designed to inhibit nuclear factor kappa-B (NF-kappaB) binding to target sequence, the second to increase estrogen receptor (ER) alpha expression. We found that both decoy molecules are potent inducers of apoptosis of human OCs, associated with increase of caspase 3 activity and decrease of interleukin 6 expression. In addition, we provide evidence indicating that these oligonucleotides are active in vivo in inducing OCs apoptosis. Because OCs are essential for skeletal development and remodeling throughout the life of animal and man, the approach described is of potential clinical importance. PMID- 17341641 TI - Competition effects shape the response sensitivity and kinetics of phosphorylation cycles in cell signaling. AB - Phosphorylation cycles are a core component of cell signaling networks. The response sensitivity and kinetics of these cycles are controlled by thermodynamic, kinetic, and structural factors, including binding affinities, catalytic activities, and the phosphorylation order of multiple sites. Based on mathematical models, we interpret the role of these factors in terms of competition effects. For the regulation of a single phosphorylation site, two kinds of competition effects turn out to shape behavior: the competition between kinase and phosphatase to bind the substrate, and the competition between the distinct phosphorylation forms of the substrate for binding to either enzyme. Depending on the concentrations and mutual affinities of the enzymes and the target, the response function can be graded, ultrasensitive, or biphasic. In multiply phosphorylatable proteins, additional factors generating competition effects are present and more complex responses can be obtained. For example, the combination of a cooperative kinetics with the conditions for zero-order ultrasensitivity may yield a bistable response. We show that a repeated competition between kinase and phosphatase for binding the substrate and/or between the phosphorylation and dephosphorylation reactions at each phosphorylation site generally result in a threshold response. The phosphorylation time is also strongly affected by the kinetic design of the cycle. In particular, threshold responses are generally associated with very long phosphorylation times. We also argue here that a description in terms of elementary binding and reaction steps is required for an appropriate analysis of these cycles in cell signaling. PMID- 17341642 TI - Preparation of leptin antagonists by site-directed mutagenesis of human, ovine, rat, and mouse leptin's site III: implications on blocking undesired leptin action in vivo. AB - Six muteins of human, ovine, rat, and mouse leptins mutated to Ala in amino acids 39-41 or 39-42 were prepared by site-directed mutagenesis of the putative site III, which does not affect binding but is necessary for receptor activation, then expressed, solubilized in 4.5 M urea, at pH 11.3 in presence of cysteine, refolded and purified to homogeneity by anion-exchange chromatography on Q Sepharose or combination of anion-exchange chromatography followed by gel filtration. The overall yields were 400-800 mg from 5 L of fermentation. All proteins were >98% pure as evidenced by SDS-PAGE and contained at least 95% monomers as documented by gel-filtration chromatography under nondenaturing conditions. Circular dichroism analysis revealed that all six muteins have identical secondary structure characteristic of nonmutated leptins, namely 52-63% of alpha helix content. All muteins formed a 1:1 complex with chicken leptin binding domain, (chLBD) and bound chLBD or membrane-embedded leptin receptor with affinity identical to WT leptins. Muteins were devoid of any biological activity in several bioassays but were potent competitive antagonists. Some muteins were pegylated using 40 kDa PEG. Although pegylation decreased the in vitro activity, increasing circulation half-life can recompensate this deficit, so pegylated antagonists are expected to be more potent in vivo. PMID- 17341643 TI - Dual activity of phosphorothioate CpG oligodeoxynucleotides on HIV: reactivation of latent provirus and inhibition of productive infection in human T cells. AB - CpG oligodeoxynucleotides (CpG ODNs) bind to toll-like receptor-9 (TLR-9) and activate immune cells with antigen-presenting activity, including B cells and dendritic cells. Here we show that treatment of the latently human immunodeficiency virus (HIV)-infected T cell line ACH-2 with the CpG ODNs 2006 or 2040 triggers activation of viral gene expression, demonstrating that CpG signaling activity can also be found in T cells. The CpG ODNs g12AAC and g12GTC had no effect on virus reactivation. In contrast to the stimulating effects on viral gene expression in latently infected cells, CpG ODNs potently suppressed HIV replication in productively infected MT4 T cells or PBLs. Inhibition of virus replication was not related to the CpG motif but similarly occurred with non-CpG phosphorothioate (PTO)-ODNs. Thus, virus inhibition was likely caused by the PTO backbone of the CpG ODNs, probably by interfering with events prior to integration of the viral cDNA into the host genome. The ability of CpG PTO-ODNs to trigger reactivation of latent HIV in combination with their antiviral activity on productive infection makes this substance class an interesting candidate for further test to asses their potential as supplements in HIV therapy. PMID- 17341644 TI - Prostanoids with cyclopentenone structure as tools for the characterization of electrophilic lipid-protein interactomes. AB - Electrophilic eicosanoids arise from the free radical-induced peroxidation of arachidonic acid or its metabolites. These reactive species may play an important role in pathophysiological processes associated with inflammation and oxidative stress. Cyclopentenone prostaglandins (cyPG) and isoprostanes are reactive eicosanoids that can form covalent adducts with cysteine residues in proteins through Michael addition. In pharmacological studies, cyPG have shown potent protective effects in experimental models of inflammation and tissue injury, and they have been proposed to contribute to inflammatory resolution. An important mechanism for the anti-inflammatory effects of cyPG is the covalent modification of critical cysteine residues in proteins involved in the modulation of inflammation, such as transcription factors NF-kappaB and AP-1. In recent years, analogs of electrophilic prostanoids have been used in various approaches to identify biologically relevant protein targets for this modification. Prostanoids with cyclopentenone structure have been shown to target a defined subproteome that is beginning to be characterized. Structural studies suggest that diverse cyPG may modify distinct proteins selectively. Functional studies put forward a dual role for these compounds in the cellular response to inflammation or stress. Therefore, a detailed knowledge of targets of electrophilic eicosanoids and the functional consequences of their modification will contribute to the understanding of their mechanism of action and help assess whether these endogenous mediators can be exploited as the basis for the development of novel therapeutic strategies. In this article we discuss the recent advances in this rapidly growing field. PMID- 17341645 TI - Brain death by a thousand hypoxic cuts in sleep. PMID- 17341646 TI - The new IGRA and the old TST: making good use of disagreement. PMID- 17341647 TI - Update in pediatric lung disease 2006. PMID- 17341648 TI - Update in tuberculosis 2006. PMID- 17341649 TI - Silent brain infarction and platelet activation in obstructive sleep apnea. AB - RATIONALE: Silent brain infarction (SBI) and increased levels of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) are associated with an increased risk of cerebrovascular disease. OBJECTIVES: The aim of this study was to evaluate whether SBI and serum levels of sCD40L and sP-selectin are increased in patients with obstructive sleep apnea (OSA). METHODS: SBI was studied by brain magnetic resonance images in 50 male patients with OSA and 15 obese male control subjects who were free of comorbidities. In addition, the effects of 3 months of treatment with nasal continuous positive airway pressure (nCPAP) on serum parameters were studied in 24 patients with moderate to severe OSA. MEASUREMENTS AND MAIN RESULTS: The percentage of SBI in patients with moderate to severe OSA (25.0%) was higher than that of obese control subjects (6.7%) or patients with mild OSA (7.7%). Serum levels of sCD40L and sP-selectin were significantly higher in patients with moderate to severe OSA than in obese control subjects (p < 0.05) or patients with mild OSA (p < 0.05). In addition, nCPAP significantly decreased serum levels of sCD40L (p < 0.03) and sP-selectin (p < 0.01) in patients with moderate to severe OSA. CONCLUSIONS: These results suggest that serum levels of sCD40L and sP-selectin are elevated and SBI is more common in patients with moderate to severe OSA, leading to elevated cerebrovascular morbidity. Moreover, nCPAP may be useful for decreasing risk in patients with moderate to severe OSA. PMID- 17341650 TI - Racemic = R enantiomer: a dual citation. PMID- 17341651 TI - How much smoke do we need in order to assume that there is a fire? PMID- 17341652 TI - Natural and enantiomeric etiocholanolone interact with distinct sites on the rat alpha1beta2gamma2L GABAA receptor. AB - We have studied the ability of the androgen etiocholanolone and its enantiomer (ent-etiocholanolone) to modulate rat alpha1beta2gamma2L GABA(A) receptor function transiently expressed in human embryonic kidney cells. Studies on steroid enantiomer pairs can yield powerful new information on the pharmacology of steroid interactions with the GABA(A) receptor. Both steroids enhance currents elicited by GABA, but ent-etiocholanolone is much more powerful than etiocholanolone at producing potentiation. At a low GABA concentration (0.5 microM, or= epinephrine >6-fluoronorepinephrine > norepinephrine >>> phenylephrine. Finally, equilibrium dissociation constants (K(b)) of selective alphaAR antagonists were functionally determined to confirm the specific alpha(2)AR subtype inhibiting CA3 epileptiform activity. Apparent K(b) values calculated for atipamezole (1.7 nM), MK-912 (4.8 nM), BRL-44408 (15 nM), yohimbine (63 nM), ARC-239 (540 nM), prazosin (4900 nM), and terazosin (5000 nM) correlated best with affinities previously determined for the alpha(2A)AR subtype (r = 0.99, slope = 1.0). These results suggest that, under conditions of impaired GABAergic inhibition, activation of alpha(2A)ARs is primarily responsible for the antiepileptic actions of norepinephrine in the rat hippocampal CA3 region. PMID- 17341654 TI - Pharmacology of alpha-conotoxin MII-sensitive subtypes of nicotinic acetylcholine receptors isolated by breeding of null mutant mice. AB - Subtypes of nicotinic acetylcholine receptors (nAChR) containing alpha6 subunits comprise 25 to 30% of the presynaptic nAChRs expressed in striatal dopaminergic terminals in rodents and 70% in monkeys. This class of receptors, potentially important in nicotine addiction, binds alpha-conotoxin MII (alpha-CtxMII) with high affinity and is heterogeneous, consisting of several subtypes in mice, possibly an important consideration for the design of compounds that selectively activate or antagonize the alpha6 subclass of nAChRs. Selected-null mutant mice were bred to generate isolated subtypes of alpha6beta2* nAChRs expressed in vivo for assessing pharmacology of alpha6beta2* nAChRs. Binding to striatal membranes and function in synaptosomes from (alpha4-/-)(beta3+/+) and (alpha4-/-)(beta3-/-) mice were measured and compared with wild-type (alpha4+/+)(beta3+/+) mice. Gene deletions (alpha4 and beta3) decreased binding of (125)I-alpha-CtxMII without affecting affinity for alpha-CtxMII or inhibition of alpha-CtxMII binding by epibatidine or nicotine. Deletion of the alpha4 subunit substantially increased EC(50) values for both nicotine- and cytisine-stimulated alpha-CtxMII-sensitive dopamine release from striatal synaptosomes. A further increase in EC(50) values was seen upon the additional deletion of the beta3 subunit. The data indicate that one alpha-CtxMII-sensitive nAChR subtype, prevalent on wild-type dopaminergic terminals, has the lowest EC(50) for a nicotine-mediated function so far measured in mice. In conclusion, the gene deletion strategy enabled isolation of alpha6* subtypes, and these nAChR subtypes exhibited differential activation by nicotine and cytisine. PMID- 17341655 TI - PTEN, more than the AKT pathway. AB - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/AKT constitute an important pathway regulating the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation and cell growth. PTEN is a dual protein/lipid phosphatase and its main substrate phosphatidyl-inositol 3,4,5 triphosphate (PIP3) is the product of PI3K. Increase in PIP3 recruits AKT to the membrane where is activated by other kinases also dependent on PIP3. Many components of this pathway have been described as causal forces in cancer. PTEN activity is lost by mutations, deletions or promoter methylation silencing at high frequency in many primary and metastatic human cancers. Germ line mutations of PTEN are found in several familial cancer predisposition syndromes. Recently, many activating mutations in the PI3KCA gene (coding for the p110alpha catalytic subunit of PI3K) have been described in human tumors. Activation of PI3K and AKT are reported to occur in breast, ovarian, pancreatic, esophageal and other cancers. Genetically modified mice confirm these PTEN activities. Tissue-specific deletions of PTEN usually provoke cancer. Moreover, an absence of PTEN cooperates with an absence of p53 to promote cancer. However, we have observed very different results with the expression of activated versions of AKT in several tissues. Activated AKT transgenic lines do not develop tumors in breast or prostate tissues and do not cooperate with an absence of p53. This data suggest that an AKT-independent mechanism contributes to PTEN tumorigenesis. Crosses with transgenic mice expressing possible PTEN targets indicate that neither cyclin D1 nor p53 are these AKT-independent targets. However, AKT is more than a passive bridge toward PTEN tumorigenesis, since its expression not only allows but also enforces and accelerates the tumorigenic process in combination with other oncogenes. PMID- 17341656 TI - Inhibition of vinyl carbamate-induced mutagenicity and clastogenicity by the garlic constituent diallyl sulfone in F1 (Big Blue x A/J) transgenic mice. AB - Vinyl carbamate (VC) is a metabolite of ethyl carbamate (EC), a naturally occurring compound found in fermented foods and alcoholic beverages. CYP2E1 mediates the sequential oxidation of EC to VC and subsequently to the vinyl carbamate epoxide, which is believed to be the ultimate carcinogenic species. Here, we have tested the hypothesis that bioactivation of VC by CYP2E1 plays a central role in the development of its mutagenicity and clastogenicity, and further that inhibition of CYP2E1 by diallyl sulfone (DASO(2)) leads to diminution in their incidences. DASO(2) is a garlic constituent that is oxidized by CYP2E1, leading to inactivation of this P450. F(1) (Big Blue x A/J) transgenic mice harboring the lambda cII gene were used for in vivo identification and quantitation of mutations in the lung and small intestine. Mice were pre-treated with DASO(2) (12.5-200 mg/kg, p.o.), treated 2 h later with VC (60 mg/kg, i.p.) and were killed 4 weeks later. Our results showed that pre-treatment of mice with DASO(2) at doses of 50-200 mg/kg significantly decreased the VC-induced mutant frequencies (MFs) by 50-70%. In the small intestine, pre-treatment with 200 mg/kg of DASO(2) decreased the MF by approximately 40%. Clastogenicity, as assessed by the frequency of micronucleated reticulocytes, was significantly decreased (33 44%) by pre-treatment with DASO(2) (50-200 mg/kg). These results demonstrated that bioactivation of VC by CYP2E1 plays a valid role in the development of mutagenicity and clastogenicity, and further that inhibition of this pathway by DASO(2) produces a protective effect. PMID- 17341657 TI - Targeting survivin in cancer therapy: fulfilled promises and open questions. AB - Survivin is a bifunctional protein that acts as a suppressor of apoptosis and plays a central role in cell division. The protein is strongly expressed in the most common human neoplasms, has prognostic relevance for some of them and appears to be involved in tumor cell resistance to anticancer agents and ionizing radiation. On the basis of these findings, survivin has been proposed as an attractive target for new anticancer interventions. Several preclinical studies have demonstrated that down-regulation of survivin expression or function, accomplished by means of various strategies, reduced tumor growth potential, increased the apoptotic rate and sensitized tumor cells to chemotherapeutic drugs and radiation in different human tumor models. Moreover, the first survivin inhibitors recently entered clinical trials. Recent studies suggest a possible role for survivin in regulating the function of normal adult cells. However, the expression and function of survivin in normal tissues are still not well characterized and understood. Better knowledge of the role of survivin in tumor versus normal cells will be instrumental for the design of optimal strategies to selectively disrupt survivin in cancer. PMID- 17341658 TI - CTLA-4 gene and susceptibility to human papillomavirus-16-associated cervical squamous cell carcinoma in Taiwanese women. AB - Human papillomavirus (HPV) is considered to be a necessary but not sufficient cause for cervical cancer. The host immunogenetic background plays an important role in the persistence of HPV infection and subsequent development of cervical cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed mainly on activated T cells and is important in the down-regulation of T-cell activation. The aim of this study was to determine if polymorphisms of the CTLA-4 gene are associated with HPV-induced cervical cancer in Taiwanese women. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype -318 C/T, +49 A/G and CT60 A/G polymorphisms in 144 women with cervical squamous cell carcinoma (CSCC) and 378 ethnicity-matched healthy control women. The presence and genotypes of HPV in CSCC were determined by E6-, E7-based nested polymerase chain reaction. The frequency of C/T genotype of -318 C/T polymorphism was significantly higher in patients with HPV-16-positive CSCC compared with controls (odds ratio = 1.99, 95% confidence interval = 1.16-3.42, P(c) = 0.03). No significant associations were found for +49 A/G and CT60 A/G polymorphisms. Analysis of haplotypes, computationally inferred from genotype data, also revealed no significant differences in distribution among all subjects with CSCC, those with HPV-16-positive CSCC and controls. Our results suggest that the -318 C/T variant in the promoter region of the CTLA-4 gene is associated with HPV-16 associated CSCC in Taiwanese women. PMID- 17341659 TI - Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma DU145 cells. AB - Transcription factor signal transducer and activator of transcription (Stat)-3 is activated constitutively in prostate cancer (PCA) suggesting that its disruption could be an effective approach to control this malignancy. Here we assessed whether silibinin, a flavanone from Silybum marianum with proven anticancer efficacy in various cancer models, inhibits Stat3 activation in DU145 cells, and if it does, what is the biological fate of the cells? At 50 muM or higher concentrations for 24 or 48 h, silibinin concentration dependently reduced constitutive Stat3 phosphorylation at Tyr705 and Ser727 residues under both serum and serum-starved conditions. Constitutively active Stat3-DNA binding was also inhibited concentration dependently by silibinin; however, apoptotic death together with caspase and poly(ADP-ribose) polymerase (PARP) cleavage was observed by silibinin only under serum-starved conditions suggesting that additional survival pathways are active under serum conditions. In other studies, cells were treated with various specific pharmacological inhibitors where phosphorylation of Stat3 was not reduced by epidermal growth factor receptor and Mitogen activated protein/extracellular signal regulate kinase kinase (MEK1/2) inhibitors, suggesting lack of significant roles of these in Stat3 activation in DU145 cells. Janus kinase (JAK)-1 and JAK2 inhibitors strongly reduced Stat3 phosphorylation but did not result in apoptotic cell death. Interestingly, JAK1 inhibitor only in combination with silibinin resulted in a complete reduction in Stat3 phosphorylation at Tyr705, activated caspase-9 and caspase-3, and caused strong PARP cleavage and apoptotic death of DU145 cells. Given a critical role of Stat3 activation in PCA, our results showed that silibinin inhibits constitutively active Stat3 and induces apoptosis in DU145 cells, and thus might have potential significance in therapeutic intervention of this deadly malignancy. PMID- 17341660 TI - A modified host-cell reactivation assay to measure repair of alkylating DNA damage for assessing risk of lung adenocarcinoma. AB - The nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lung adenocarcinoma through formation of DNA adducts. Our previous research on susceptibility to tobacco-induced carcinogenesis focused on benzo[a]pyrene diol epoxide (BPDE) as the in vitro mutagen for phenotype measurements of DNA repair capacity (DRC) in mammalian cells. Here, we present a modified host-cell reactivation (HCR) assay to measure lymphocytic DRC for alkylating DNA damage as is induced by the tobacco-specific nitrosamine, NNK. We substituted dimethyl sulfate (DMS) to create alkylating damage in pCMVluc plasmid DNA and established the damage-repair dose-response curves in both normal and nucleotide excision repair-deficient lymphoblastoid cell lines and in phytohemagglutinin (PHA)-stimulated primary lymphocytes. We then successfully measured the DRC in PHA-stimulated lymphocytes from 48 patients with lung adenocarcinoma and 45 cancer-free controls and tested our hypothesis that lower DRC for alkylating damage is associated with an increased risk of lung adenocarcinoma. The cases exhibited a lower mean DRC than did the controls. A >3 fold increased risk (odds ratio = 3.21; 95% confidence interval = 1.25-8.21) was found for those with DRC levels below the control median. There was no correlation between the DRC measured with this DMS-HCR assay and that from the parallel BPDE-HCR assay. Interestingly, risk increased to >10-fold for those with sub-optimal DRC measured by both DMS- and BPDE-HCR assays. We conclude that variability in DRC is a risk factor for lung cancer and our results provide proof of principle for a new assay that can assess DRC for NNK-induced DNA damage. PMID- 17341661 TI - Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. AB - In elderly patients with acute myeloid leukemia (AML) treated intensively, no best postremission strategy has emerged yet. This clinical trial enrolled 416 patients with AML aged 65 years or older who were considered eligible for standard intensive chemotherapy, with a first randomization comparing idarubicin with daunorubicin for all treatment sequences. After induction, an ambulatory postremission strategy based on 6 consolidation cycles administered monthly in outpatients was randomly compared with an intensive strategy with a single intensive consolidation course similar to induction. Complete remission (CR) rate was 57% with 10% induction deaths, and estimated overall survival was 27% at 2 years and 12% at 4 years, without notable differences between anthracycline arms. Among the 236 patients who reached CR, 164 (69%) were randomized for the postremission comparison. In these patients, the multivariate odds ratio in favor of the ambulatory arm was 1.51 for disease-free survival (P.05) and 1.59 for overall survival from CR (P.04). Despite repeated courses of chemotherapy associated with a longer time under treatment, the ambulatory arm was associated with significantly shorter rehospitalization duration and lower red blood cell unit and platelet transfusion requirements than observed in the intensive arm. In conclusion, more prolonged ambulatory treatment should be preferred to intensive chemotherapy as postremission therapy in elderly patients with AML reaching CR after standard intensive remission induction. PMID- 17341662 TI - Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study. AB - The clinical impact of MLL partial tandem duplication (MLL-PTD) was evaluated in 238 adults aged 18 to 59 years with cytogenetically normal (CN) de novo acute myeloid leukemia (AML) who were treated intensively on similar Cancer and Leukemia Group B protocols 9621 and 19808. Twenty-four (10.1%) patients harbored an MLL-PTD. Of those, 92% achieved complete remission (CR) compared with 83% of patients without MLL-PTD (P=.39). Neither overall survival nor disease-free survival significantly differed between the 2 groups (P=.67 and P=.55, respectively). Thirteen MLL-PTD(+) patients relapsed within 1.4 years of achieving CR. MLL-PTD(+) patients who relapsed more often had other adverse CN AML-associated molecular markers. In contrast with previously reported studies, 9 (41%) MLL-PTD(+) patients continue in long-term first remission (CR1; range, 2.5 7.7 years). Intensive consolidation therapy that included autologous peripheral stem-cell transplantation during CR1 may have contributed to the better outcome of this historically poor-prognosis group of CN-AML patients with MLL-PTD. PMID- 17341663 TI - Roles of RabGEF1/Rabex-5 domains in regulating Fc epsilon RI surface expression and Fc epsilon RI-dependent responses in mast cells. AB - RabGEF1/Rabex-5, a guanine nucleotide exchange factor (GEF) for the endocytic pathway regulator, Rab5, contains a Vps9 domain, an A20-like zinc finger (ZnF) domain, and a coiled coil domain. To investigate the importance of these domains in regulating receptor internalization and cell activation, we lentivirally delivered RabGEF1 mutants into RabGEF1-deficient (-/-) mast cells and examined Fc epsilon RI-dependent responses. Wild-type RabGEF1 expression corrected phenotypic abnormalities in -/- mast cells, including decreased basal Fc epsilon RI expression, slowed Fc epsilon RI internalization, elevated IgE + Ag-induced degranulation and IL-6 production, and the decreased ability of -/- cytosol to support endosome fusion. We showed that RabGEF1's ZnF domain has ubiquitin ligase activity. Moreover, the coiled coil domain of RabGEF1 is required for Rabaptin-5 binding and for maintaining basal levels of Rabaptin-5 and surface Fc epsilon RI. However, mutants lacking either of these domains normalized phenotypic abnormalities in IgE + antigen-activated -/- mast cells. By contrast, correction of these -/- phenotypes required a functional Vps9 domain. Thus, Fc epsilon RI mediated mast cell functional activation is dependent on RabGEF1's GEF activity. PMID- 17341664 TI - Malarial anemia: of mice and men. AB - Severe malaria is manifest by a variety of clinical syndromes dependent on properties of both the host and the parasite. In young infants, severe malarial anemia (SMA) is the most common syndrome of severe disease and contributes substantially to the considerable mortality and morbidity from malaria. There is now growing evidence, from both human and mouse studies of malaria, to show that anemia is due not only to increased hemolysis of infected and clearance of uninfected red blood cells (RBCs) but also to an inability of the infected host to produce an adequate erythroid response. In this review, we will summarize the recent clinical and experimental studies of malaria to highlight similarities and differences in human and mouse pathology that result in anemia and so inform the use of mouse models in the study of severe malarial anemia in humans. PMID- 17341665 TI - Hsp72 up-regulates Epstein-Barr virus EBNALP coactivation with EBNA2. AB - The Epstein-Barr virus (EBV) transcriptional coactivator EBNALP specifically associates and colocalizes with Hsp72 in lymphoblastoid cell lines. We now find that overexpression of Hsp72 more than doubled EBNALP coactivation with EBNA2 of a transfected EBV LMP1 promoter in B lymphoblasts, did not affect EBNA2 or EBNALP protein levels, and strongly up-regulated EBNA2 and EBNALP coactivation of LMP1 protein expression from the endogenous EBV genome in latency I infected Akata cells. The Hsp72 ATP, protein binding, and the C-terminal regulatory domains were required for full activity. An EBNALP deletion mutant, EBNALPd45, which does not associate with Hsp72, coactivated with EBNA2, but was not affected by Hsp72 overexpression, despite Hsp72 up-regulation of wild-type EBNALP coactivation with EBNA2 at all levels of EBNALP expression, indicating the importance of Hsp72 association with EBNALP for Hsp72 up-regulation of coactivation. Of importance, a 90% RNAi knockdown of Hsp72 reduced EBNALP coactivation with EBNA2 of transfected EBV LMP1 and Cp promoters by approximately 50%. Overexpression of the Hsp72 C terminal interacting and regulatory protein, CHIP, strongly down-regulated EBNALP coactivation, independently of CHIP ubiquitin ligase activity. CHIP effects were Hsp72 dependent, indicating a background downmodulating role for CHIP in Hsp72 augmentation of EBNA2 and EBNALP coactivation. Based on these and other cited data, we favor a model in which Hsp72 chaperones EBNALP shuttling of repressors from EBNA2-enhanced promoters. PMID- 17341668 TI - Stubby elliptocytes are an invariable feature of leukoerythroblastosis. PMID- 17341666 TI - Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors. AB - Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis with potential for progression to acute myeloid leukemia (AML). We compared natural killer (NK) cytolytic function in 48 MDS patients with 37 healthy donors and found reduced activity in the patient population (K562 cytolysis, 19% +/- 21% SD versus 40% +/- 17%) (P < .001). NK cytotoxicity in MDS patients was reduced against 3 disparate tumor targets with differential activating receptor requirement, suggesting global defects in NK function. Reduced NK function in MDS was significantly associated with higher International Prognostic Score (P = .01), abnormal karyotype (P = .05), the presence of excess blasts (P = .01), and age-adjusted bone marrow hypercellularity (P = .04). MDS patients had a display of the activating receptor NKp30, and NKG2D down-regulation closely correlated with impaired NK function (P = .001). NKG2D ligands (MICA and MICB) were expressed on CD34(+) cells from bone marrow of 30% of MDS patients and a leukemic cell line derived from an MDS patient (MDS1). Collectively, these findings suggest that impairment of NK cytolytic function derives in part from reduced activating NK receptors such as NKG2D in association with disease progression. Evasion of NK immunosurveillance may have importance for MDS disease progression. PMID- 17341669 TI - Applications of porous tantalum in total hip arthroplasty. PMID- 17341670 TI - Understanding shoulder and elbow injuries in baseball. AB - Repetitive overhead throwing exerts significant mechanical stress on the shoulder and elbow joint; this stress can lead to developmental anatomic changes in the young thrower. Asymptomatic pathology in the shoulder and elbow joint is prevalent and, with overuse, can progress to disabling injury. Joint injury occurs as a result of the body's inability to properly coordinate motion segments during the pitching delivery, leading to further structural damage. Identifying and preventing overuse is the key to avoiding injury, particularly in the young pitcher. Injury prevention and rehabilitation should center on optimizing pitching mechanics, core strength, scapular control, and joint range of motion. PMID- 17341671 TI - Optimal duration of prophylaxis for venous thromboembolism following total hip arthroplasty and total knee arthroplasty. AB - Elective total hip arthroplasty and total knee arthroplasty are associated with a high risk of postoperative venous thromboembolism. Traditionally, antithrombotic prophylaxis has been administered during the hospital stay. However, with patients spending less time in the hospital after surgery, there is a need to continue thromboprophylaxis beyond hospital discharge. The current recommendation for prophylaxis in total joint arthroplasty patients is a minimum of 10 days, with extended prophylaxis up to 28 to 35 days following total hip arthroplasty. Prophylaxis with low-molecular-weight heparins for approximately 4 weeks following hip arthroplasty has resulted in clinically significant reductions in the incidence of venographically confirmed deep vein thrombosis. Currently, no data support extended thromboprophylaxis beyond 10 days following total knee arthroplasty. Using weighted risk factors to assess individual risk for venous thromboembolism can help the physician determine the optimal duration of prophylaxis. PMID- 17341672 TI - Ophthalmologic complications associated with prone positioning in spine surgery. AB - Visual impairment and blindness associated with general anesthesia and prone positioning in spine surgery have been increasing in incidence over the past several decades. Corneal abrasion, the most common ophthalmologic injury, is usually self-limiting. However, prolonged surgical procedures (>7 hours) associated with acute blood loss anemia, hypotension, and hypoxia may lead to posterior ischemic optic neuropathies. Direct pressure to the periorbital region of the eye can cause increased intraocular pressure and blindness as the result of central retinal artery occlusion. Hypoxia and cerebral embolism are associated with occipital cortical infarct or cortical blindness. The prognosis for visual recovery from ischemic neuropathy and retinal artery occlusion is poor. Cortical blindness usually improves to varying degrees. Effective treatment of perioperative amaurosis is lacking and usually ineffective, making prevention the cornerstone of management. To best prevent permanent ophthalmologic complications associated with prone positioning during spine surgery, orthopaedic surgeons should be aware of pathophysiology and related risks associated with spine surgery in the prone position, and initiate preventive measures and predictable treatment options. PMID- 17341673 TI - Corticosteroid injections in the treatment of trigger finger: a level I and II systematic review. AB - Trigger finger is a tendinitis (stenosing tenosynovitis) with multiple management approaches. We conducted an evidence-based medicine systematic review of level I and II prospective randomized controlled trials to determine the effectiveness of corticosteroid injection in managing trigger finger. MEDLINE, Cochrane database, and secondary references were reviewed to locate all English-language prospective randomized controlled trials evaluating trigger finger treatment. Four studies using injectable corticosteroids were identified, based on the following inclusion criteria: all were prospective randomized controlled trials of adults with >85% follow-up. This review indicates that the incidence of trigger finger is greatest in women (75%), with an average patient age range of 52 to 62 years. Combined analysis of these four studies shows that corticosteroid injections are effective in 57% of patients. PMID- 17341674 TI - Pediatric pelvic fractures. AB - Pediatric pelvic fractures account for only 1% to 2% of fractures seen by orthopaedic surgeons who treat children. They are typically associated with high energy trauma, requiring a comprehensive workup for concomitant life-threatening injuries. Anteroposterior radiographs and rapid-sequence computed tomography are the standards of diagnostic testing to identify the fracture and recognize associated injuries. Treatment is individualized based on patient age, fracture classification, stability of the pelvic ring, extent of concomitant injuries, and hemodynamic stability of the patient. Most pelvic injuries in children are treated nonsurgically, with protected weight bearing and gradual return to activity. Open reduction and internal fixation is required for acetabular fractures with >2 mm of fracture displacement and for any intra-articular or triradiate cartilage fracture displacement >2 mm. To prevent limb-length discrepancies, external fixation is necessary for pelvic ring displacement >2 cm. Fractures involving immature triradiate cartilage may lead to growth disturbance of the acetabulum, resulting in acetabular dysplasia, hip subluxation, or hip joint incongruity. Osteonecrosis of the femoral head may develop after acetabular fractures associated with hip dislocation. Other complications include myositis ossificans and neurologic deficits secondary to sciatic, femoral, and/or lumbosacral plexus nerve injuries. PMID- 17341675 TI - Indications for orthoses to improve gait in children with cerebral palsy. AB - Orthoses are frequently used to improve the gait of children with cerebral palsy. Optimal clinical decision-making for improving gait through orthotic management requires an understanding of the biomechanics of the foot and ankle during normal gait, the pathophysiology and pathomechanics of gait disruption in children with cerebral palsy, and the biomechanical characteristics of various orthoses. The clinician must seek to integrate his or her own goals with those of the child and family, the therapist, and the orthotist. Design, indications, and cost should be considered when choosing an orthosis. The physician can construct a paradigm for clinical decision-making, focusing on the evaluation of ankle/foot alignment, range of motion, and assessment of dynamic gait deviations. This paradigm will guide the clinician in the use of orthoses to improve gait in children with cerebral palsy. For optimal orthotic management, the physician must clearly identify the gait deviation and functional deficits to be addressed with the orthosis. The outcome of the orthotic intervention should be documented as objectively as possible. PMID- 17341676 TI - Proximal interphalangeal joint arthroplasty. PMID- 17341677 TI - Food and Drug Administration public hearing on the conduct of emergency clinical research: testimony of Dr. Pepe--defending the rights of all individuals to have access to potential life-saving therapies and resuscitation studies. PMID- 17341678 TI - Transgenic expression of a dominant negative K(ATP) channel subunit in the mouse endothelium: effects on coronary flow and endothelin-1 secretion. AB - K(ATP) channels are involved in regulating coronary function, but the contribution of endothelial K(ATP) channels remains largely uncharacterized. We generated a transgenic mouse model to specifically target endothelial K(ATP) channels by expressing a dominant negative Kir6.1 subunit only in the endothelium. These animals had no obvious overt phenotype and no early mortality. Histologically, the coronary endothelium in these animals was preserved. There was no evidence of increased susceptibility to ergonovine-induced coronary vasospasm. However, isolated hearts from these animals had a substantially elevated basal coronary perfusion pressure. The K(ATP) channel openers, adenosine and levcromakalim, decreased the perfusion pressure whereas the K(ATP) channel blocker glibenclamide failed to produce a vasoconstrictive response. The inducible endothelial nitric oxide pathway was intact, as evidenced by vasodilation caused by bradykinin. In contrast, basal endothelin-1 release was significantly elevated in the coronary effluent from these hearts. Treatment of mice with bosentan (endothelin-1 receptor antagonist) normalized the coronary perfusion pressure, demonstrating that the elevated endothelin-1 release was sufficient to account for the increased coronary perfusion pressure. Pharmacological blockade of K(ATP) channels led to elevated endothelin-1 levels in the coronary effluent of isolated mouse and rat hearts as well as enhanced endothelin-1 secretion from isolated human coronary endothelial cells. These data are consistent with a role for endothelial K(ATP) channels to control the coronary blood flow by modulating the release of the vasoconstrictor, endothelin 1. PMID- 17341679 TI - Tau-4R suppresses proliferation and promotes neuronal differentiation in the hippocampus of tau knockin/knockout mice. AB - Differential isoform expression and phosphorylation of protein tau are believed to regulate the assembly and stabilization of microtubuli in fetal and adult neurons. To define the functions of tau in the developing and adult brain, we generated transgenic mice expressing the human tau-4R/2N (htau-4R) isoform on a murine tau null background, by a knockout/knockin approach (tau-KOKI). The main findings in these mice were the significant increases in hippocampal volume and neuronal number, which were sustained throughout adult life and paralleled by improved cognitive functioning. The increase in hippocampal size was found to be due to increased neurogenesis and neuronal survival. Proliferation and neuronal differentiation were further analyzed in primary hippocampal cultures from tau KOKI mice, before and after htau-4R expression onset. In absence of tau, proliferation increased and both neurite and axonal outgrowth were reduced. Htau 4R expression suppressed proliferation, promoted neuronal differentiation, and restored neurite and axonal outgrowth. We suggest that the tau-4R isoform essentially contributes to hippocampal development by controlling proliferation and differentiation of neuronal precursors. PMID- 17341680 TI - Low expression of COX-2, reduced cumulus expansion, and impaired ovulation in SULT1E1-deficient mice. AB - The SULT1E1-encoded estrogen sulfotransferase (EST) catalyzes sulfation of estrogen, resulting in its inactivation. Reduced fertility observed in SULT1E1 knockout (KO) female mice has previously been attributed to the deleterious effect of chronic exposure to high levels of circulating estrogen on placental function. We herein suggest that, in addition to placental dysfunction, this phenotype demonstrates that an excess of estrogen impairs ovulation. The role of SULT1E1 in ovulation is suggested by the substantially low ovulatory response in hCG-treated SULT1E1 KO mice; a similar effect was observed when 17beta-estradiol was administered to wild-type (WT) females. The normal rate of ovulation in SULT1E1 KO females may be restored by PGE2. Along this line, ovaries of human Chorionic Gonadotropin (hCG)-treated SULT1E1 KO mice expressed low levels of cyclooxygenase-2 (COX-2) and its downstream TSG6; moreover, their ovaries contained a reduced number of expanded cumuli. Our results demonstrate, for the first time, that estrogen inactivation may allow the expression of COX-2 and subsequent cumulus expansion, enabling normal ovulation. Our findings may be applied to novel treatments of human ovulatory failure. PMID- 17341681 TI - Oral vaccination with a viral vector containing Abeta cDNA attenuates age-related Abeta accumulation and memory deficits without causing inflammation in a mouse Alzheimer model. AB - Immunotherapy with Abeta is expected to bring great improvement for Alzheimer disease (AD). However, clinical trials have been suspended because of meningoencephalitics, which accompanied lymphocytic infiltration. We have developed an oral vaccine for AD with a recombinant adeno-associated viral vector carrying Abeta cDNA (AAV/Abeta). The vaccine reduces the amount of Abeta deposited without lymphocytic infiltration in APP transgenic (Tg2576) mice. In the present study, Tg2576 mice showed progressive cognitive impairments in the novel object recognition test, Y-maze test, water maze test, and contextual conditioned fear learning test. A single oral administration of AAV/Abeta to Tg2576 mice at the age of 10 months alleviated progressive cognitive impairment with decreased Abeta deposition, insoluble Abeta, soluble Abeta oligomer (Abeta*56), microglial attraction, and synaptic degeneration induced in the brain regions at the age of 13 months. A histological analysis with hematoxylin and eosin and an immunohistochemical analysis with antibodies against CD3, CD4, CD8, and CD19 suggested there was no lymphocytic infiltration or microhemorrhage in the brain of AAV/Abeta-vaccinated Tg2576 mice at 13 months of age. Taken together, these results suggest that immunotherapy with AAV/Abeta is a safe and effective treatment for AD. PMID- 17341682 TI - 5-Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNA. AB - The known functions of folate are to support one-carbon metabolism and to serve as photoreceptors for cryptochromes and photolyases. We demonstrate that 5 methyltetrahydrofolate (5-MTHF, the predominant folate in plasma) is also a potent, near diffusion limited, scavenger of singlet oxygen and quencher of excited photosensitizers. Both pathways result in decomposition of 5-MTHF, although ascorbate can protect against this loss. In the absence of photosensitizers, 5-MTHF is directly decomposed only very slowly by UVA or UVB. Although synthetic folic acid can promote DNA damage by UVA, submicromolar 5-MTHF inhibits photosensitization-induced strand breaks. These observations suggest a new role for reduced folate in protection from ultraviolet damage and have bearing on the hypothesis that folate photodegradation influenced the evolution of human skin color. PMID- 17341683 TI - A new microrheometric approach reveals individual and cooperative roles for TGF beta1 and IL-1beta in fibroblast-mediated stiffening of collagen gels. AB - The stiffness of the extracellular matrix can profoundly influence cell and tissue behaviors. Thus there is an emerging emphasis on understanding how matrix mechanical environments are established, regulated, and modified. Here we develop a microrheometric assay to measure the mechanical properties of a model extracellular matrix (type I collagen gel) and use it to explore cytokine induced, cell-mediated changes in matrix mechanical properties. The microrheometric assay uses micron-scale ferrimagnetic beads embedded within collagen gels during fibrillogenesis. The beads are magnetized, then subjected to a twisting field, with the aggregate rotation of the beads measured by a magnetometer. The degree of bead rotation reflects the stiffness of the surrounding matrix. We show that the microscale assay provides stiffness measures for collagen gels comparable to those obtained with standard macroscale rheometry. To demonstrate the utility of the assay for biological discovery, we measure stiffness changes in fibroblast-populated collagen gels exposed to three concentrations of six cytokines over 2 to 14 days. Among the cytokines tested, transforming growth factor-beta1 and interleukin-1beta enhanced matrix stiffness, and together exerted cooperative effects on cellular modulation of matrix mechanics. The microrheometry approach developed here should accelerate the discovery of biological pathways orchestrating cellular modulation of matrix mechanics. PMID- 17341684 TI - Creation of a genetic model of obesity in a teleost. AB - The adipostat is the mechanism by which the brain detects and maintains constant levels of energy stored in adipocytes in the form of lipids. Key elements of the adipostat include the adipocyte-derived hormone leptin that is expressed in proportion to energy levels and serves to communicate this information to the central nervous system and the central circuits, which sense and respond to leptin. Blockade of one of these circuits, the central melanocortin system, disrupts leptin action and causes a distinct obesity syndrome in mice and humans, characterized by increased adiposity as well as increased linear growth. We show here that transgenic zebrafish overexpressing the endogenous melanocortin antagonist agouti-related protein (AgRP) also exhibit obesity, increased linear growth, and adipocyte hypertrophy. These findings demonstrate that key elements of the adipostat originated before the evolution of mammals. Furthermore, transgenic overexpression of AgRP in zebrafish yields a new model system for the genetic analysis of energy homeostasis in a simple vertebrate system. PMID- 17341685 TI - Hypoxia inducible factor regulates the cardiac expression and secretion of apelin. AB - Apelin and its G-protein-coupled receptor APJ have various beneficial effects on cardiac function and blood pressure. The mechanisms that regulate apelin gene expression are not known. Because apelin gene expression has been shown to increase in cardiac ischemia, we investigated if apelin (Apln) gene expression was sensitive to hypoxia. Here we show that hypoxia increases the apelin expression in rat myocardium and in cultured cardiomyocytes. Pharmacological activation of hypoxia inducible factor by desferrioxamine (DFO) or expression of a constitutively active form of HIF-1alpha increased apelin expression in cardiomyocyte cultures. The induction of apelin by hypoxia was abolished on transient expression of the HIF inhibitory PAS protein in cardiomyocytes. Increased apelin expression induced by hypoxia or DFO was accompanied by the processing of the cellular storage form proapelin into smaller apelin peptides and increased secretion of these biologically active forms of apelin. In a rat in vivo model, acute myocardial infarction (24 h) led to a transient increase in ventricular apelin mRNA levels. Our results indicate that apelin gene is regulated by hypoxia in cardiac myocytes via the HIF pathway, suggesting a role for apelin as a potential marker for acute cardiac hypoxia with a possible compensatory role in myocardial tissue suffering from oxygen deprivation. PMID- 17341686 TI - Eurythermalism and the temperature dependence of enzyme activity. AB - The "Equilibrium Model" has provided new tools for describing and investigating enzyme thermal adaptation. It has been shown that the effect of temperature on enzyme activity is not only governed by deltaG(double dagger)(cat) and deltaG(double dagger)(inact) but also by two new intrinsic parameters, deltaH(eq) and T(eq), which describe the enthalpy and midpoint, respectively, of a reversible equilibrium between active and inactive (but not denatured) forms of enzyme. Twenty-one enzymes from organisms with a wide range of growth temperatures were characterized using the Equilibrium Model. Statistical analysis indicates that T(eq) is a better predictor of growth temperature than enzyme stability (deltaG(double dagger)(inact)). As expected from the Equilibrium Model, deltaH(eq) correlates with catalytic temperature tolerance of enzymes and thus can be declared the first intrinsic and quantitative measure of enzyme eurythermalism. Other findings shed light on the evolution of psychrophilic and thermophilic enzymes. The findings suggest that the description of the Equilibrium Model of the effect of temperature on enzyme activity applies to all enzymes regardless of their temperature origins and that its associated parameters, deltaH(eq) and T(eq), are intrinsic and necessary parameters for characterizing the thermal properties of enzymes and their temperature adaptation and evolution. PMID- 17341687 TI - The sphingosine 1-phosphate receptor S1P2 triggers hepatic wound healing. AB - Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK1 and 2). We previously showed that S1P receptors (S1P1, S1P2, and S1P3) are expressed in hepatic myofibroblasts (hMF), a population of cells that triggers matrix remodeling during liver injury. Here we investigated the function of these receptors in the wound healing response to acute liver injury elicited by carbon tetrachloride, a process that associates hepatocyte proliferation and matrix remodeling. Acute liver injury was associated with the induction of S1P2, S1P3, SphK1, and SphK2 mRNAs and increased SphK activity, with no change in S1P1 expression. Necrosis, inflammation, and hepatocyte regeneration were similar in S1P2-/- and wild-type (WT) mice. However, compared with WT mice, S1P2-/- mice displayed reduced accumulation of hMF, as shown by lower induction of smooth muscle alpha-actin mRNA and lower induction of TIMP-1, TGF-beta1, and PDGF-BB mRNAs, overall reflecting reduced activation of remodeling in response to liver injury. The wound healing response was similar in S1P3-/- and WT mice. In vitro, S1P enhanced proliferation of cultured WT hMF, and PDGF-BB further enhanced the mitogenic effect of S1P. In keeping with these findings, PDGF-BB up-regulated S1P2 and SphK1 mRNAs, increased SphK activity, and S1P2 induced PDGF-BB mRNA. These effects were blunted in S1P2-/- cells, and S1P2-/- hMF exhibited reduced mitogenic and comitogenic responses to S1P. These results unravel a novel major role of S1P2 in the wound healing response to acute liver injury by a mechanism involving enhanced proliferation of hMF. PMID- 17341688 TI - Endocytosis machinery is involved in aggregation of proteins with expanded polyglutamine domains. AB - The cell's failure to refold or break down abnormal polypeptides often leads to their aggregation, which could cause toxicity and various pathologies. Here we investigated cellular factors involved in protein aggregation in yeast and mammalian cells using model polypeptides containing polyglutamine domains. In yeast, a number of mutations affecting the complex responsible for formation of the endocytic vesicle reduced the aggregation. Components of the endocytic complex (EC) Sla1, Sla2, and Pan1 were seen as clusters in the polyglutamine aggregates. These proteins associate with EC at the later stages of its maturation. In contrast, Ede1 and Ent1, the elements of EC at the earlier stages, were not found in the aggregates, suggesting that late ECs are involved in polyglutamine aggregation. Indeed, stabilization of the late complexes by inhibition of actin polymerization enhanced aggregation of polypeptides with polyglutamine domains. Similarly, in mammalian cells, inhibitors of actin polymerization, as well as depletion of a mediator of actin polymerization, Arp2, strongly enhanced the aggregation. In contrast, destabilization of EC by depletion or inhibition of a scaffolding protein N-WASP effectively suppressed the aggregation. Therefore, EC appears to play a pivotal role in aggregation of cytosolic polypeptides with polyglutamine domains in both yeast and mammalian cells. PMID- 17341689 TI - Binding of elastin peptides to S-Gal protects the heart against ischemia/reperfusion injury by triggering the RISK pathway. AB - Elastin peptides (EPs) generated by hydrolysis of elastic fibers by elastinolytic enzymes display a wide spectrum of biological activities. Here, we investigated their influence on rat heart ischemia-mediated injury using the Langendorff ex vivo model. EPs, i.e., kappa elastin, at 1.32- and 660-nM concentrations, when administered before the ischemia period, elicited a beneficial influence against ischemia by accelerating the recovery rate of heart contractile parameters and by decreasing significantly creatine kinase release and heart necrosis area when measured at the onset of the reperfusion. All effects were S-Gal-dependent, as being reproduced by (VGVAPG)3 and as being inhibited by receptor antagonists, such as lactose and V14 peptide (VVGSPSAQDEASPL). EPs interaction with S-Gal triggered NO release and activation of PI3-kinase/Akt and ERK1/2 in human coronary endothelial cells (HCAECs) and rat neonatal cardiomyocytes (RCs). This signaling pathway, as designated as RISK, for reperfusion injury salvage kinase pathway, was shown to be responsible for the beneficial influence of EPs on ischemia/reperfusion injury on the basis of its inhibition by specific pharmacological inhibitors. EPs survival activity was attained at a concentration averaging that present into the blood circulation, supporting the contention that these matrikines might offer a natural protection against cardiac injury in young and adult individuals. Such protective effect might be lost with aging, since we found that hearts from 24-month-old rats did not respond to EPs. PMID- 17341690 TI - Improved method for the analysis of membrane proteins by mass spectrometry. AB - Membrane-bound and membrane-associated proteins are difficult to analyze by mass spectrometry, since the association with lipids impedes the isolation and solubilization of the proteins in buffers suitable for mass spectrometry and the efficient generation of positively charged peptide ions by electrospray ionization. Current methods mostly utilize detergents for the isolation of proteins from membranes. In this study, we present an improved detergent-free method for the isolation and mass spectrometric identification of membrane-bound and membrane-associated proteins. We delipidate proteins from the membrane bilayer by chloroform extraction to overcome dissolution and ionization problems during analysis. Comparison of our results to results obtained by direct tryptic digestion of insoluble membrane pellets identifies an increased number of membrane proteins, and a higher quality of the resulting mass spectral data. PMID- 17341691 TI - Electroacupuncture suppresses myostatin gene expression: cell proliferative reaction in mouse skeletal muscle. AB - Complementary and alternative medicine (CAM) may provide patients with an alternative to traditional medicine, but an assessment of its efficacy is required. One CAM method, electroacupuncture (EA) treatment, is a maneuver that utilizes stimulation of acupuncture needles with a low-frequency microcurrent. To study the effect of short-term EA, we evaluated the differential expression of genes induced by EA in mouse skeletal muscle for up to 24 h. We then used RT-PCR to confirm the expression patterns of six differentially expressed genes. Bioinformatics analysis of their transcription control regions showed that EA inducible genes have numerous common binding motifs that are related to cell differentiation, cell proliferation, muscle repair, and hyperplasia. These results suggested that EA treatment may induce cell proliferation in skeletal muscle. To verify this possibility, we used EA to stimulate mouse skeletal muscle daily for up to 1 mo and examined the long-term effects. Immunohistochemical analysis showed that nuclei of muscle cells treated with EA for 1 mo, especially nuclei of satellite cells, reacted with anti-human PCNA. Also, expression of the gene encoding myostatin, which is a growth repressor in muscle satellite cells, was suppressed by daily EA treatment for 1 wk; EA treatment for 1 mo resulted in more marked suppression of the gene. These molecular findings constitute strong evidence that EA treatment suppresses myostatin expression, which leads to a satellite cell-related proliferative reaction and repair in skeletal muscle. PMID- 17341692 TI - Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors. AB - The role of diet in the prevention of breast cancer is widely accepted, yet little is known about how its biological effects mitigate susceptibility to this disease. Soy consumption is associated with reduced breast cancer risk in women, an effect largely attributed to the soy isoflavone genistein (Gen). We previously showed reduced incidence of chemically induced mammary tumors in young adult rats with lifetime dietary intake of soy protein isolate (SPI) than in those fed the control diet containing casein (Cas). To gain insight into signaling pathways underlying dietary tumor protection, we performed genome-wide expression profiling of mammary epithelial cells from young adult rats lifetime fed Cas, SPI, or Cas supplemented with Gen. We identified mammary epithelial genes regulated by SPI (79 total) and Gen (96 total) using Affymetrix rat 230A GeneChip arrays and found minimal overlap in gene expression patterns. We showed that the regulated transcripts functionally clustered in biochemical pathways involving metabolism, immune response, signal transduction, and ion transport. We confirmed the differential expression of Wnt (Wnt5a, Sfrp2) and Notch (Notch2, Hes1) signaling components by SPI and/or Gen using quantitative real-time PCR. Wnt pathway inhibition by Gen was supported by reduced cyclin D1 immunoreactivity in mammary ductal epithelium of Gen relative to Cas and SPI groups, despite comparable levels of membrane-localized E-cadherin and beta-catenin. Identification of distinct Gen and SPI responsive genes in mammary epithelial cells may define early events contributing to tumor protection by diet relevant to the prevention of breast and other types of cancer. PMID- 17341693 TI - Functional polymorphism in human CYP4F2 decreases 20-HETE production. AB - 20-Hydroxyeicosatetraenoic acid (20-HETE) plays an important role in the regulation of renal tubular and vascular function and a deficiency in the renal formation of 20-HETE has been linked to the development of hypertension. The cytochrome P450 4F2 (CYP4F2) gene encodes for the major CYP enzyme responsible for the synthesis of 20-HETE in the human kidney. We screened two human sampling panels (African and European Americans: n = 24 and 23 individuals, respectively) using PCR and DNA resequencing to identify informative SNPs in the coding region of the CYP4F2 gene. Two nonsynonymous SNPs that lead to amino acid changes at position 12 (W12G) and 433 (V433M), were identified. Both of these variants were found to be frequent in both African and European American sampling panels (9-21% minor allele frequency), and the W12G polymorphism exhibited extensive linkage disequilibrium with surrounding SNPs. To determine the functional significance of these mutations on the ability of the CYP4F2 enzyme to metabolize arachidonic acid and leukotriene B(4) (LTB(4)), recombinant baculoviruses containing four different human CYP4F2 variants (i.e., W12/V433, W12/M433, G12/V433, G12/M433) were generated and the proteins were expressed in Sf9 insect cells. The presence of the M433 allele, W12/M433, or G12/M433 decreased 20-HETE production to 56-66% of control. In contrast these variants had no effect on the omega-hydroxylation of LTB(4). These findings are the first to identify a functional variant in the human CYP4F2 gene that alters the production of 20-HETE. PMID- 17341694 TI - The cover. Noah's Ark. PMID- 17341696 TI - Chronic wound care guidelines issued. PMID- 17341695 TI - MicroRNAs linked to pancreatic cancer. PMID- 17341697 TI - Researchers critical of TV drug ads. PMID- 17341698 TI - CDC: autism spectrum disorders common. PMID- 17341703 TI - HIV screening and false-positive results. PMID- 17341704 TI - HIV screening and false-positive results. PMID- 17341705 TI - PSA screening and elderly men. PMID- 17341706 TI - Advanced prostate cancer and postoperative radiotherapy. PMID- 17341707 TI - Advanced prostate cancer and postoperative radiotherapy. PMID- 17341708 TI - Political activity of US physicians. PMID- 17341709 TI - Computed tomography screening and lung cancer outcomes. AB - CONTEXT: Current and former smokers are currently being screened for lung cancer with computed tomography (CT), although there are limited data on the effect screening has on lung cancer outcomes. Randomized controlled trials assessing CT screening are currently under way. OBJECTIVE: To assess whether screening may increase the frequency of lung cancer diagnosis and lung cancer resection or may reduce the risk of a diagnosis of advanced lung cancer or death from lung cancer. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal analysis of 3246 asymptomatic current or former smokers screened for lung cancer beginning in 1998 either at 1 of 2 academic medical centers in the United States or an academic medical center in Italy with follow-up for a median of 3.9 years. INTERVENTION: Annual CT scans with comprehensive evaluation and treatment of detected nodules. MAIN OUTCOME MEASURES: Comparison of predicted with observed number of new lung cancer cases, lung cancer resections, advanced lung cancer cases, and deaths from lung cancer. RESULTS: There were 144 individuals diagnosed with lung cancer compared with 44.5 expected cases (relative risk [RR], 3.2; 95% confidence interval [CI], 2.7-3.8; P<.001). There were 109 individuals who had a lung resection compared with 10.9 expected cases (RR, 10.0; 95% CI, 8.2-11.9; P<.001). There was no evidence of a decline in the number of diagnoses of advanced lung cancers (42 individuals compared with 33.4 expected cases) or deaths from lung cancer (38 deaths due to lung cancer observed and 38.8 expected; RR, 1.0; 95% CI, 0.7-1.3; P = .90). CONCLUSIONS: Screening for lung cancer with low-dose CT may increase the rate of lung cancer diagnosis and treatment, but may not meaningfully reduce the risk of advanced lung cancer or death from lung cancer. Until more conclusive data are available, asymptomatic individuals should not be screened outside of clinical research studies that have a reasonable likelihood of further clarifying the potential benefits and risks. PMID- 17341710 TI - Opening of specialty cardiac hospitals and use of coronary revascularization in medicare beneficiaries. AB - CONTEXT: Although proponents argue that specialty cardiac hospitals provide high quality cost-efficient care, strong financial incentives for physicians at these facilities could result in greater procedure utilization. OBJECTIVE: To determine whether the opening of cardiac hospitals was associated with increasing population-based rates of coronary revascularization. DESIGN, SETTING, AND PATIENTS: In a study of Medicare beneficiaries from 1995 through 2003, we calculated annual population-based rates for total revascularization (coronary artery bypass graft [CABG] plus percutaneous coronary intervention [PCI]), CABG, and PCI. Hospital referral regions (HRRs) were used to categorize health care markets into those where (1) cardiac hospitals opened (n = 13), (2) new cardiac programs opened at general hospitals (n = 142), and (3) no new programs opened (n = 151). MAIN OUTCOME MEASURES: Rates of change in total revascularization, CABG, and PCI using multivariable linear regression models with generalized estimating equations. RESULTS: Overall, rates of change for total revascularization were higher in HRRs after cardiac hospitals opened when compared with HRRs where new cardiac programs opened at general hospitals and HRRs with no new programs (P<.001 for both comparisons). Four years after their opening, the relative increase in adjusted rates was more than 2-fold higher in HRRs where cardiac hospitals opened (19.2% [95% confidence interval {CI}, 6.1%-32.2%], P<.001) when compared with HRRs where new cardiac programs opened at general hospitals (6.5% [95% CI, 3.2%-9.9%], P<.001) and HRRs with no new programs (7.4% [95% CI, 3.2% 11.5%], P<.001). These findings were consistent when rates for CABG and PCI were considered separately. For PCI, this growth appeared largely driven by increased utilization among patients without acute myocardial infarction (42.1% [95% CI, 21.4%-62.9%], P<.001). CONCLUSION: The opening of a cardiac hospital within an HRR is associated with increasing population-based rates of coronary revascularization in Medicare beneficiaries. PMID- 17341711 TI - Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. AB - CONTEXT: Popular diets, particularly those low in carbohydrates, have challenged current recommendations advising a low-fat, high-carbohydrate diet for weight loss. Potential benefits and risks have not been tested adequately. OBJECTIVE: To compare 4 weight-loss diets representing a spectrum of low to high carbohydrate intake for effects on weight loss and related metabolic variables. DESIGN, SETTING, AND PARTICIPANTS: Twelve-month randomized trial conducted in the United States from February 2003 to October 2005 among 311 free-living, overweight/obese (body mass index, 27-40) nondiabetic, premenopausal women. INTERVENTION: Participants were randomly assigned to follow the Atkins (n = 77), Zone (n = 79), LEARN (n = 79), or Ornish (n = 76) diets and received weekly instruction for 2 months, then an additional 10-month follow-up. MAIN OUTCOME MEASURES: Weight loss at 12 months was the primary outcome. Secondary outcomes included lipid profile (low-density lipoprotein, high-density lipoprotein, and non-high-density lipoprotein cholesterol, and triglyceride levels), percentage of body fat, waist hip ratio, fasting insulin and glucose levels, and blood pressure. Outcomes were assessed at months 0, 2, 6, and 12. The Tukey studentized range test was used to adjust for multiple testing. RESULTS: Weight loss was greater for women in the Atkins diet group compared with the other diet groups at 12 months, and mean 12 month weight loss was significantly different between the Atkins and Zone diets (P<.05). Mean 12-month weight loss was as follows: Atkins, -4.7 kg (95% confidence interval [CI], -6.3 to -3.1 kg), Zone, -1.6 kg (95% CI, -2.8 to -0.4 kg), LEARN, -2.6 kg (-3.8 to -1.3 kg), and Ornish, -2.2 kg (-3.6 to -0.8 kg). Weight loss was not statistically different among the Zone, LEARN, and Ornish groups. At 12 months, secondary outcomes for the Atkins group were comparable with or more favorable than the other diet groups. CONCLUSIONS: In this study, premenopausal overweight and obese women assigned to follow the Atkins diet, which had the lowest carbohydrate intake, lost more weight at 12 months than women assigned to follow the Zone diet, and had experienced comparable or more favorable metabolic effects than those assigned to the Zone, Ornish, or LEARN diets [corrected] While questions remain about long-term effects and mechanisms, a low-carbohydrate, high-protein, high-fat diet may be considered a feasible alternative recommendation for weight loss. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00079573. PMID- 17341712 TI - Major and minor ECG abnormalities in asymptomatic women and risk of cardiovascular events and mortality. AB - CONTEXT: Data are sparse regarding the prevalence, incidence, and independent prognostic value of minor and/or major electrocardiographic (ECG) abnormalities in asymptomatic postmenopausal women. There is no information on the effect, if any, of hormonal treatment on the prognostic value of the ECG. OBJECTIVE: To examine association of minor and major baseline and incident ECG abnormalities with long-term cardiovascular morbidity and mortality. DESIGN, SETTING, AND PARTICIPANTS: Post-hoc analysis of the estrogen plus progestin component of the Women's Health Initiative study, a randomized controlled primary prevention trial of 14 749 postmenopausal asymptomatic women with intact uterus who received 1 daily tablet containing 0.625 mg of oral conjugated equine estrogen and 2.5 mg of medroxyprogesterone acetate or a matching placebo. Participants were enrolled from 1993 to 1998, and the estrogen plus progestin trial was stopped on July 7, 2002. MAIN OUTCOME MEASURES: The Novacode criteria were used to define minor, major, and incident ECG abnormalities. Cardiovascular end points included incident coronary heart disease (CHD) and cardiovascular disease (CVD) events. RESULTS: Among women with absent (n = 9744), minor (n = 4095), and major (n = 910) ECG abnormalities, there were 118, 91, and 37 incident CHD events, respectively. The incident annual CHD event rates per 10 000 women with absent, minor, or major ECG abnormalities were 21 (95% confidence interval [CI], 18-26), 40 (95% CI, 32-49), and 75 (95% CI, 54-104), respectively. After 3 years of follow-up, 5% of women who had normal ECG at baseline developed new ECG abnormalities with an annual CHD event rate of 85 (95% CI, 44-164) per 10 000 women. The adjusted hazard ratios for CHD events were 1.55 (95% CI, 1.14-2.11) for minor baseline, 3.01 (95% CI, 2.03-4.46) for major baseline, and 2.60 (95% CI, 1.08-6.27) for incident ECG abnormalities. There were no significant interactions between hormone treatment assignment and ECG abnormalities for risk prediction of cardiovascular end points. For prediction of CHD events, the addition of ECG findings to the Framingham risk score increased from 0.69 to 0.74 the area under the receiver operating characteristic curve. Similar findings were found for incident CVD events. CONCLUSIONS: Among asymptomatic postmenopausal women, clinically relevant baseline and incident ECG abnormalities are independently associated with increased risk of cardiovascular events and mortality, and the information is incremental to the established method of risk stratification. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611. PMID- 17341713 TI - Aging, adiposity, and calorie restriction. AB - CONTEXT: Excessive calorie intake and subsequent obesity increases the risk of developing chronic disease and decreases life expectancy. In rodent models, calorie restriction with adequate nutrient intake decreases the risk of developing chronic disease and extends maximum life span. OBJECTIVE: To evaluate the physiological and clinical implications of calorie restriction with adequate nutrient intake. EVIDENCE ACQUISITION: Search of PubMed (1966-December 2006) using terms encompassing various aspects of calorie restriction, dietary restriction, aging, longevity, life span, adiposity, and obesity; hand search of journals that focus on obesity, geriatrics, or aging; and search of reference lists of pertinent research and review articles and books. Reviewed reports (both basic science and clinical) included epidemiologic studies, case-control studies, and randomized controlled trials, with quality of data assessed by taking into account publication in a peer-reviewed journal, number of animals or individuals studied, objectivity of measurements, and techniques used to minimize bias. EVIDENCE SYNTHESIS: It is not known whether calorie restriction extends maximum life span or life expectancy in lean humans. However, calorie restriction in adult men and women causes many of the same metabolic adaptations that occur in calorie-restricted rodents and monkeys, including decreased metabolic, hormonal, and inflammatory risk factors for diabetes, cardiovascular disease, and possibly cancer. Excessive calorie restriction causes malnutrition and has adverse clinical effects. CONCLUSIONS: Calorie restriction in adult men and women causes beneficial metabolic, hormonal, and functional changes, but the precise amount of calorie intake or body fat mass associated with optimal health and maximum longevity in humans is not known. In addition, it is possible that even moderate calorie restriction may be harmful in specific patient populations, such as lean persons who have minimal amounts of body fat. PMID- 17341714 TI - CT screening for lung cancer: spiraling into confusion? PMID- 17341715 TI - Physician-owned specialty hospitals and coronary revascularization utilization: too much of a good thing? PMID- 17341716 TI - JAMA patient page. Lung cancer. PMID- 17341717 TI - Sex-differential expression of ornithine aminotransferase in the mouse kidney. AB - The mouse kidney expresses the gene of ornithine aminotransferase (Oat). Previous works suggest that Oat is differentially expressed in female and male mouse kidney (Alonso E, Rubio V. Biochem J 259: 131-138, 1989; Levillain O, Diaz JJ, Blanchard O, Dechaud H. Endocrinology 146: 950-959, 2005; Manteuffel-Cymborowska M, Chmurzynska W, Peska M, Grzelakowska-Sztabert B. Int J Biochem Cell Biol 27: 287-295, 1995; Natesan S, Reddy SR. Comp Biochem Physiol B Biochem Mol Biol 130: 585-595, 2001; Yu H, Yoo PK, Aguirre CC, Tsoa RW, Kern RM, Grody WW, Cederbaum SD, Iyer RK. J Histochem Cytochem 51: 1151-1160, 2003). This study was designed to provide a detailed description of the sexual dimorphism of Oat expression in the mouse kidney and to test the influence of sex hormones on its regulation. Experiments were performed on male and female Swiss OF1 mice during their postnatal development, at adulthood, and in orchidectomized and ovariectomized mice. Kidneys, dissected renal zones, and mitochondria were used to analyze OAT mRNA and protein levels and measure OAT activity. The results revealed that before puberty, Oat expression was similar between female and male kidneys whereas from puberty until adulthood Oat expression increased in the female kidney, becoming approximately 2.5-fold higher than in the male kidney. This sex differential expression of Oat was associated with a sex-specific distribution of Oat along the corticopapillary axis and within the nephron. OAT was three- to fourfold more expressed in the female than the male cortex. In males, Oat was highly expressed in the medulla, mainly in the thick ascending limbs. Renal Oat distribution in orchidectomized mice resembled that in the females. Ovariectomy did not influence Oat expression. Sex differences are explained by the physiological increase in plasma testosterone in males. Expression of medium chain acyl-CoA synthetase protein confirmed this finding. We report sexual dimorphism of Oat expression in the mouse kidney and show that Oat is naturally downregulated in the presence of testosterone. PMID- 17341718 TI - Comparison of protective effects of trimetazidine against experimental warm ischemia of different durations: early and long-term effects in a pig kidney model. AB - Acute renal failure (ARF) is often the consequence of an ischemia-reperfusion injury (IRI) and associated with high mortality. Warm ischemia (WI) is a crucial factor of tissue damage, and tissue destruction led by ischemia-reperfusion (I/R) can impact the early and long-term functional outcome. Trimetazidine (TMZ) is an anti-ischemic drug. Previously, we already verified its protective effect on a cold-ischemic pig kidney model by directly adding TMZ into the preservation solution (Faure JP, Baumert H, Han Z, Goujon JM, Favreau F, Dutheil D, Petit I, Barriere M, Tallineau C, Tillement JP, Carretier M, Mauco G, Papadopoulos V, Hauet T. Biochem Pharmacol 66: 2241-2250, 2003; Faure JP, Petit I, Zhang K, Dutheil D, Doucet C, Favreau F, Eugene M, Goujon JM, Tillement JP, Mauco G, Vandewalle A, Hauet T. Am J Transplant 4: 495-504, 2004). In this study, we aimed to study the potential effect of TMZ pretreatment (5 mg/kg iv 24 h before WI) on the injury caused by WI for 45, 60, and 90 min and reperfusion in a WI pig kidney model. Compared with sham-operated (control) and uninephrectomized animals (UNX), TMZ pretreatment significantly reduced deleterious effects after 45 min, and particularly 60 and 90 min, of WI by improving the recovery of renal function and minimizing the inflammatory response commonly prevalent in ischemic kidney injury. Compared with controls (control group and UNX group), it was observed that 1) hypoxia-inducible factor-1 (HIF-1alpha) expression occurred earlier and with a higher intensity in the TMZ-treated groups; 2) the reduction of IRI during the first week following reperfusion was correlated with an earlier and greater expression of stathmin, which is involved in the process of tubular repair; and 3) the tubulointerstitial fibrosis was reduced, particularly after 60 and 90 min of WI. In conclusion, TMZ made the warm-ischemic kidneys more resistant to the deleterious impact of a single episode of I/R and reduced early and long-term subsequent damage. PMID- 17341719 TI - Endotoxins in lung cancer prevention. PMID- 17341720 TI - Local recurrence or cardiovascular disease: pay now or later. PMID- 17341721 TI - National Cancer Act: a look back and forward. PMID- 17341722 TI - Stat bite: Currently approved oncology drugs. PMID- 17341723 TI - NIH common fund concerns some in cancer research community. PMID- 17341724 TI - Governments move to improve quality and cut costs. PMID- 17341725 TI - Lapatinib moves forward in inflammatory and early HER2-positive breast cancer trials. PMID- 17341726 TI - SERMs: meeting the promise of multifunctional medicines. AB - The successful development and clinical evaluation of the selective estrogen receptor modulators in the Study of Tamoxifen and Raloxifene trial provides an occasion to reflect on the milestone that has been achieved and the potential for further progress in the chemoprevention of breast cancer. The evolution of tamoxifen from a successful treatment for breast cancer to the first chemopreventive for any cancer took two decades. Clinicians gained an enormous amount of experience with the use of tamoxifen as a treatment, and, as a result, there were few surprises in terms of efficacy or the side effect profile when the medicine was used to prevent breast cancer in high-risk women. In contrast, raloxifene emerged via the novel path of the evidence-based hypothesis that a drug targeted at one disease, osteoporosis, could also prevent breast cancer. Changes in health care strategies to implement chemoprevention take time, but the evidence now suggests that chemoprevention has become a reality in clinical practice. PMID- 17341727 TI - Lung cancer risk among female textile workers exposed to endotoxin. AB - BACKGROUND: Reduced risk of lung cancer among workers in the cotton textile industry has been observed since the 1970s. Bacterial endotoxin, a contaminant of raw cotton fiber and cotton dust, has been proposed as a protective agent that may act through the innate and acquired immune systems. We examine the association between endotoxin exposure and lung cancer risk in a cohort of female textile workers. METHODS: We conducted a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China. We compared the cumulative exposure histories of 628 case patients diagnosed with incident lung cancer from January 1, 1989, through December 31, 1998, with those of a lung cancer-free reference subcohort of 3184 workers who were frequency matched by 5-year age groups to all cancer patients in the cohort. Cumulative endotoxin exposure for all participants was based on historic measurements and on additional measurements for this study. Relative risks and 95% confidence intervals (CIs) were estimated by hazard ratios (HRs) from Cox proportional hazards models. We conducted exposure-response trend analyses by use of cumulative exposures with lag times of 0, 5, 10, 15, or 20 years to account for disease latency. All analyses controlled for age and smoking status. All statistical tests were two sided. RESULTS: Cumulative exposure to endotoxin was strongly, statistically significantly, and inversely associated with lung cancer risk. The inverse trend was greatest with a 20-year lag time, for which highest endotoxin exposure was associated with a statistically significantly 40% less risk of lung cancer (HR = 0.60, 95% CI = 0.43 to 0.83; P(trend) across quintiles = .002) than non-exposure. From a reported population rate of lung cancer among women in Shanghai of 19.1 per 100,000 for the year 2000 and the estimated reduction in risk of lung cancer observed for 20 years of endotoxin exposure in this population of workers, the incidence of lung cancer in this cohort was reduced by approximately 7.6 per 100,000 (range = 3.2-10.9 per 100,000). CONCLUSIONS: Long-term and high-level exposure to endotoxin, compared with no exposure, appears to be associated with a reduced risk of lung cancer in this cohort. PMID- 17341728 TI - Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. AB - BACKGROUND: Radiotherapy for breast cancer as delivered in the 1970s has been associated with increased risk of cardiovascular disease, but recent studies of associations with modern regimens have been inconclusive. Few data on long-term cardiovascular disease risk according to specific radiation fields are available, and interaction with known cardiovascular risk factors has not been examined. METHODS: We studied treatment-specific incidence of cardiovascular disease in 4414 10-year survivors of breast cancer who were treated from 1970 through 1986. Risk of cardiovascular disease in these patients was compared with general population rates and evaluated in Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: After a median follow-up of 18 years, 942 cardiovascular events were observed (standardized incidence ratio = 1.30, 95% confidence interval [CI] = 1.22 to 1.38; corresponding to 62.9 excess cases per 10,000 patient-years). Breast irradiation only was not associated with increased risk of cardiovascular disease. However, radiotherapy to either the left or right side of the internal mammary chain was associated with increased cardiovascular disease risk for the treatment period 1970-1979 (for myocardial infarction, hazard ratio [HR] = 2.55, 95% CI = 1.55 to 4.19; P<.001; for congestive heart failure, HR = 1.72, 95% CI = 1.22 to 2.41; P = .002) compared with no radiotherapy. Among patients who received internal mammary chain radiotherapy after 1979, risk of myocardial infarction declined over time toward unity, whereas the risks of congestive heart failure (HR = 2.66, 95% CI = 1.27 to 5.61; P = .01) and valvular dysfunction (HR = 3.17, 95% CI = 1.90 to 5.29; P<.001) remained increased. Patients who underwent radiotherapy plus adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) after 1979 had a higher risk of congestive heart failure than patients who were treated with radiotherapy only (HR = 1.85, 95% CI = 1.25 to 2.73; P = .002). Smoking and radiotherapy together were associated with a more than additive effect on risk of myocardial infarction (HR = 3.04, 95% CI = 2.03 to 4.55; P for departure from additivity = .039). CONCLUSIONS: Radiotherapy as administered from the 1980s onward is associated with an increased risk of cardiovascular disease. Irradiated breast cancer patients should be advised to refrain from smoking to reduce their risk for cardiovascular disease. PMID- 17341729 TI - A prostate-specific antigen-activated channel-forming toxin as therapy for prostatic disease. AB - BACKGROUND: Most men will develop prostatic abnormalities, such as benign prostatic hyperplasia (BPH) or prostate cancer, as they age. Prostate-specific antigen (PSA) is a serine protease that is secreted at high levels by the normal and diseased prostate. Therapies that are activated by PSA may prove effective in treating prostatic malignancies. METHODS: We modified proaerolysin (PA), the inactive precursor of a bacterial cytolytic pore-forming protein, to produce a PSA-activated protoxin (PRX302). The viability of the prostate adenocarcinoma cell lines LNCaP, PC-3, CWR22H, and DU145 and the bladder cancer cell line TSU after treatment with PA or PRX302 in the presence or absence of purified PSA was assayed. Mice carrying xenograft tumors derived from LNCaP, CWR22H, or TSU cells were treated with intratumoral injection of PA or PRX302, and tumor size was monitored. To test the safety of PRX302, we administered it into the PSA secreting prostate glands of cynomolgus monkeys. All statistical tests were two sided. RESULTS: Native PA was highly toxic in vitro but had no tumor-specific effects in vitro or in vivo. Picomolar concentrations of PRX302 led to PSA dependent decreases in cell viability in vitro (PRX302 versus PRX302 + PSA: DU145 cells, mean viability = 78.7% versus mean = 1.6%, difference = 77.1%, 95% confidence interval [CI] = 70.6% to 86.1%; P<.001; TSU cells, mean = 100.2% versus mean = 1.4%, difference = 98.8%, 95% CI = 96.4% to 104.0%; P<.001). Single intratumoral injections of PRX302 produced substantial and often complete regression of PSA-secreting human prostate cancer xenografts (5 microg dose, complete regression in 6 of 26 mice bearing LNCap or CWR22H xenografts [23%]; 10 microg dose, complete regression in 10 of 26 mice [38.5%]) but not PSA-null bladder cancer xenografts. The prostates of cynomolgus monkeys injected with a single dose of PRX302 displayed extensive but organ-confined damage, with no toxicity to neighboring organs or general morbidity. CONCLUSIONS: Our observations demonstrate the potential safe and effective intraprostatic application of this engineered protoxin. PMID- 17341730 TI - Longitudinal measurement of clinical mammographic breast density to improve estimation of breast cancer risk. AB - BACKGROUND: Whether a change over time in clinically measured mammographic breast density influences breast cancer risk is unknown. METHODS: From January 1993 to December 2003, data that included American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density categories (1-4 in order of increasing density) were collected prospectively on 301,955 women aged 30 and older who were not using postmenopausal hormone replacement therapy and underwent at least two screening mammography examinations; 2639 of the women were diagnosed with breast cancer within 1 year of the last examination. Women's first and last BI-RADS breast density (average 3.2 years apart) and logistic regression were used to model the odds of having invasive breast cancer or ductal carcinoma in situ diagnosed within 12 months of the last examination by change in BI-RADS category. Rates of breast cancer adjusted for age, mammography registry, and time between screening examinations were estimated from this model. All statistical tests were two-sided. RESULTS: The rate (breast cancers per 1000 women) of breast cancer was higher if BI-RADS breast density category increased from 1 to 2 (5.6, 95% confidence interval [CI] = 4.7 to 6.9) or 1 to 3 (9.9, 95% CI = 6.4 to 15.5) compared to when it remained at BI-RADS density of 1 (3.0, 95% CI = 2.3 to 3.9; P<.001 for trend). Similar and statistically significant trends between increased or decreased density and increased or decreased risk of breast cancer, respectively, were observed for women whose breast density category was initially 2 or 3 and changed categories. BI-RADS density of 4 on the first examination was associated with a high rate of breast cancer (range 9.1-13.4) that remained high even if breast density decreased. CONCLUSION: An increase in BI-RADS breast density category within 3 years may be associated with an increase in breast cancer risk and a decrease in density category with a decrease in risk compared to breast cancer risk in women in whom breast density category remains unchanged. Two longitudinal measures of BI-RADS breast density may better predict a woman's risk of breast cancer than a single measure. PMID- 17341731 TI - The role of EXT1 in nonhereditary osteochondroma: identification of homozygous deletions. AB - BACKGROUND: Multiple osteochondromas is a hereditary syndrome that is characterized by the formation of cartilage-capped bony neoplasms (osteochondromas), for which exostosis (multiple)-1 (EXT1) has been identified as a causative gene. However, 85% of all osteochondromas present as solitary (nonhereditary) lesions in which somatic mutations in EXT1 are extremely rare, but loss of heterozygosity and clonal rearrangement of 8q24 (the chromosomal locus of EXT1) are common. We examined whether EXT1 might act as a classical tumor suppressor gene for nonhereditary osteochondromas. METHODS: Eight nonhereditary osteochondromas were subjected to high-resolution array-based comparative genomic hybridization (array-CGH) analysis for chromosome 8q. The array-CGH results were validated by subjecting tumor DNA to multiple ligation dependent probe amplification (MLPA) analysis for EXT1. EXT1 locus-specific fluorescent in situ hybridization (FISH) was performed on nuclei isolated from the three tissue components of osteochondroma (cartilage cap, perichondrium, bony stalk) to examine which parts of the tumor are of clonal origin. RESULTS: Array CGH analysis of tumor DNA revealed that all eight osteochondromas had a large deletion of 8q; five tumors had an additional small deletion of the other allele of 8q that contained the EXT1 gene. MLPA analysis of tumor DNA confirmed these findings and identified two additional deletions that were smaller than the limit of resolution of array-CGH. FISH analysis of the cartilage cap, perichondrium, and bony stalk showed that these homozygous EXT1 deletions were present only in the cartilage cap of osteochondroma. CONCLUSION: EXT1 functions as a classical tumor suppressor gene in the cartilage cap of nonhereditary osteochondromas. PMID- 17341733 TI - Re: Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on incidence of intra- and extrahepatic cholangiocarcinoma in the United States. PMID- 17341734 TI - Re: Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. PMID- 17341736 TI - Binge alcohol exposure in the second trimester attenuates fetal cerebral blood flow response to hypoxia. AB - Alcohol is detrimental to the developing brain and remains the leading cause of mental retardation in developed countries. The mechanism of alcohol brain damage remains elusive. Studies of neurological problems in adults have focused on alcohol's cerebrovascular effects, because alcoholism is a major risk factor for stroke and cerebrovascular injuries. However, few studies have examined similar cerebrovascular effects of fetal alcohol exposure. We examined the effect of chronic binge alcohol exposure during the second trimester on fetal cerebrovascular and metabolic responses to hypoxia in near-term sheep and tested the hypothesis that fetal alcohol exposure would attenuate cerebrovascular dilation to hypoxia. Pregnant ewes were infused with alcohol (1.5 g/kg) or saline intravenously at 60-90 days of gestation (full term = 150 days). At 125 days of gestation, we measured fetal cerebral blood flow (CBF) and oxygen metabolism at baseline and during hypoxia. Maternal blood alcohol averaged 214 +/- 5.9 mg/dl immediately after the 1.5-h infusion, with similar values throughout the month of infusion. Hypoxia resulted in a robust increase in CBF in saline-infused fetuses. However, the CBF response to hypoxia in fetuses chronically exposed to alcohol was significantly attenuated. Cerebral oxygen delivery decreased in both groups of fetuses during hypoxia but to a greater degree in the alcohol-exposed fetuses. Prenatal alcohol exposure during the second trimester attenuates cerebrovascular responses to hypoxia in the third trimester. Altered cerebrovascular reactivity might be one mechanism for alcohol-related brain damage and might set the stage for further brain injury if a hypoxic insult occurs. PMID- 17341737 TI - Adenosine enhances cytosolic phosphorylation potential and ventricular contractility in stunned guinea pig heart: receptor-mediated and metabolic protection. AB - Mechanisms of adenosine (ADO) protection of reperfused myocardium are not fully understood. We tested the hypothesis that ADO (0.1 mM) alleviates ventricular stunning by ADO A(1)-receptor stimulation combined with purine metabolic enhancements. Langendorff guinea pig hearts were stunned at constant left ventricular end-diastolic pressure by low-flow ischemia. Myocardial phosphate metabolites were measured by (31)P-NMR, with phosphorylation potential {[ATP]/([ADP].[P(i)]), where brackets indicate concentration} estimated from creatine kinase equilibrium. Creatine and IMP, glycolytic intermediates, were measured enzymatically and glycolytic flux and extracellular spaces were measured by radiotracers. All treatment interventions started after a 10-min normoxic stabilization period. At 30 min reperfusion, ventricular contractility (dP/dt, left ventricular pressure) was reduced 17-26%, ventricular power (rate-pressure product) by 37%, and [ATP]/([ADP].[P(i)]) by 53%. The selective A(1) agonist 2 chloro-N(6)-cyclo-pentyladenosine marginally preserved [ATP]/([ADP].[P(i)]) and ventricular contractility but not rate-pressure product. Purine salvage precursor inosine (0.1 mM) substantially raised [ATP]/([ADP].[P(i)]) but weakly affected contractility. The ATP-sensitive potassium channel blocker glibenclamide (50 microM) abolished ADO protection of [ATP]/([ADP].[P(i)]) and contractility. ADO raised myocardial IMP and glucose-6-phosphate, demonstrating increased purine salvage and pentose phosphate pathway flux potential. Coronary hyperemia alone (papaverine) was not cardioprotective. We found that ADO protected energy metabolism and contractility in stunned myocardium more effectively than both the A(1)-receptor agonist 2-chloro-N(6)-cyclo-pentyladenosine and the purine salvage precursor inosine. Because ADO failed to stimulate glycolytic flux, the enhancement of reperfusion, [ATP]/([ADP].[P(i)]), indicates protection of mitochondrial function. Reduced ventricular dysfunction at enhanced [ATP]/([ADP].[P(i)]) argues against opening of mitochondrial ATP-sensitive potassium channel. The results establish a multifactorial mechanism of ADO antistunning, which appears to combine ADO A(1)-receptor signaling with metabolic adenylate and antioxidant enhancements. PMID- 17341738 TI - Commentary on Viewpoint "Human experimentation: no accurate, quantitative data?". PMID- 17341739 TI - Commentary on Viewpoint "Human experimentation: no accurate, quantitative data?". PMID- 17341740 TI - Commentary on Viewpoint "Human experimentation: no accurate, quantitative data?". PMID- 17341741 TI - Commentary on Viewpoint "Human experimentation: no accurate, quantitative data?". PMID- 17341742 TI - Commentary on Viewpoint "Human experimentation: no accurate, quantitative data?". PMID- 17341743 TI - Commentary on Viewpoint "Human experimentation: no accurate, quantitative data?". PMID- 17341744 TI - Commentary on Viewpoint "Human experimentation: no accurate, quantitative data?". PMID- 17341746 TI - How can practice-based research contribute to the elimination of health disparities? AB - Racial, ethnic, and socioeconomic disparities in health care and health outcomes are well documented. Disparities research is evolving from documenting these disparities, to understanding their causes and mechanisms, and finally to conducting interventional research to reduce or eliminate disparities. Unfortunately, few studies to date have demonstrated substantial reductions in health outcomes disparities. Traditional experimental models of research that test a single intervention held constant throughout the study period may not have the power to impact complex clusters of comorbid health disparities in patients who receive care in underresourced primary care safety net practice settings. New models of research will be required to test dynamic, multidimensional interventions that triangulate on patients, providers, and communities and are continuously improved with every radar-sweep of feedback from rapid-cycle measurement of population health outcomes on a community-wide basis. In this article, we review 12 promising strategies that could substantially increase the impact of research on eliminating health disparities in America. PMID- 17341747 TI - Barriers and motivators for making error reports from family medicine offices: a report from the American Academy of Family Physicians National Research Network (AAFP NRN). AB - CONTEXT: Reporting of medical errors is a widely recognized mechanism for initiating patient safety improvement, yet we know little about the feasibility of error reporting in physician offices, where the majority of medical care in the United States is rendered. OBJECTIVE: To identify barriers and motivators for error reporting by family physicians and their office staff based on the experiences of those participating in a testing process error reporting study. DESIGN: Qualitative focus group study, analyzed using the editing method. SETTING: Eight volunteer practices of the American Academy of Family Physicians National Research Network. PARTICIPANTS: 139 physicians, nurse practitioners, physician assistants, nurses, and staff who took part in 18 focus groups. INSTRUMENT: Interview questions asked about making reports, what prevents more reports from being made, and decisions about when to make reports. RESULTS: Four factors were seen as central to making error reports: the burden of effort to report, clarity regarding the information requested in an error report, the perceived benefit to the reporter, and properties of the error (eg, severity, responsibility). The most commonly mentioned barriers were related to the high burden of effort to report and lack of clarity regarding the requested information. The most commonly mentioned motivator was perceived benefit. CONCLUSION: Successful error reporting systems for physicians' offices will need to have low reporting burden, have great clarity regarding the information requested, provide direct benefit through feedback useful to reporters, and take into account error severity and personal responsibility. PMID- 17341748 TI - Poor nutritional habits: a modifiable predecessor of chronic illness? A North Carolina Family Medicine Research Network (NC-FM-RN) study. AB - PURPOSE: To examine associations between personal nutritional patterns and various indicators of health, disease risk, and chronic illness in a diverse, representative sample of adult patients from primary care settings. METHODS: As part of a survey of adult patients conducted in the waiting rooms of 4 primary care practices in North Carolina (recruitment rate 74.8%), a 7-item nutrition screen was administered to 1788 study participants. Other questionnaire items addressed disease and functional status, race/ethnicity, health habits, and demographic factors. RESULTS: Respondents included 292 African Americans (17.3%), 1004 non-Hispanic whites (59.4%), 255 Hispanics (15.1%), and 126 American Indians (7.4%); mean age 47.5 years. Thirty percent reported eating 3 or more fast food meals weekly, 29% drank 3 or more high-sugar beverages weekly, 22% ate 3 or more high-fat snacks weekly, 36% ate 3 or more desserts weekly, 11% reported eating "a lot" of margarine, butter, or meat fat; 62% ate 2 or fewer fruits or vegetables daily; and 42% reported consuming protein less than 3 times a week. Scores on a summary measure were worse for pre-diabetics than for diabetics, for young adults compared with older persons, and for persons reporting good/excellent health versus fair/poor health. CONCLUSIONS: People at high risk for developing chronic illnesses later in life reported poorer diets in comparison with people who are already ill. This probably represents increased nutritional awareness and motivation among people with chronic diseases. Because primary care patients have a high prevalence of chronic disease risk factors, the primary care office setting may constitute a particularly appropriate location for nutrition education. PMID- 17341749 TI - Rural community members' perceptions of harm from medical mistakes: a High Plains Research Network (HPRN) Study. AB - OBJECTIVE: The aim of this study was to learn about community members' definitions and types of harm from medical mistakes. METHODS: Mixed methods study using community-based participatory research (CBPR). The High Plains Research Network (HPRN) with its Community Advisory Council (CAC) designed and distributed an anonymous survey through local community newspapers. Survey included open ended questions on patients' experiences with medical mistakes and resultant harm. Qualitative analysis was performed by CAC and research team members on mistake descriptions and types of reported harm. Patient Safety Taxonomy coding was performed on a subset of surveys that contained actual medical errors. RESULTS: A total of 286 surveys were returned, with 172 respondents (60%) reporting a total of 180 perceived medical mistakes. Quantitative analysis showed that 41% of perceived mistakes (n = 73) involved only unanticipated outcomes. Reported types of harm included emotional, financial, and physical harm. Reports suggest that perceived clinician indifference to unanticipated outcomes may lead to patients' loss of trust and belief that the unexpected outcome was a result of an error. DISCUSSION: CBPR methodology is an important strategy to design and implement a community-based survey. Community members reported experiencing medical mistakes, most with harmful outcomes. The response they received by the medical community may have influenced their perception of mistake and harm. PMID- 17341750 TI - The prevalence of dysphagia in primary care patients: a HamesNet Research Network study. AB - PURPOSE: A number of disorders cause dysphagia, which is the perception of an obstruction during swallowing. The purpose of this study was to determine the prevalence of dysphagia in primary care patients. METHODS: Adults 18 years old and older were the subjects of an anonymous survey that was collected in the clinic waiting room before patients were seen by a physician. Twelve family medicine offices in HamesNet, a research network in Georgia, participated. RESULTS: Of the 947 study participants, 214 (22.6%) reported dysphagia occurring several times per month or more frequently. Those reporting dysphagia were more likely to be women (80.8% women vs 19.2% men, P = .002) and older (mean age of 48.1 in patients with dysphagia vs mean age of 45.7 in patients without dysphagia, P = .001). Sixty-four percent of patients with dysphagia indicated that they were concerned about their symptoms, but 46.3% had not spoken with their doctor about their symptoms. Logistic regression analyses showed that increased frequency [odds ratio (OR) = 2.15, 95% CI 1.41-3.30], duration (OR = 1.91, CI 1.24-2.94), and concern (OR = 2.64, CI 1.36-5.12) of swallowing problems as well as increased problems eating out (OR = 1.72, CI 1.19-2.49) were associated with increased odds of having talked to a physician. CONCLUSIONS: This is the first report of the prevalence of dysphagia in an unselected adult primary care population. Dysphagia occurs commonly in primary care patients but often is not discussed with a physician. PMID- 17341751 TI - The "Measuring Outcomes of Clinical Connectivity" (MOCC) trial: investigating data entry errors in the Electronic Primary Care Research Network (ePCRN). AB - INTRODUCTION: The electronic Primary Care Research Network (ePCRN) enrolled PBRN researchers in a feasibility trial to test the functionality of the network's electronic architecture and investigate error rates associated with two data entry strategies used in clinical trials. METHODS: PBRN physicians and research assistants who registered with the ePCRN were eligible to participate. After online consent and randomization, participants viewed simulated patient records, presented as either abstracted data (short form) or progress notes (long form). Participants transcribed 50 data elements onto electronic case report forms (CRFs) without integrated field restrictions. Data errors were analyzed. RESULTS: Ten geographically dispersed PBRNs enrolled 100 members and completed the study in less than 7 weeks. The estimated overall error rate if field restrictions had been applied was 2.3%. Participants entering data from the short form had a higher rate of correctly entered data fields (94.5% vs 90.8%, P = .004) and significantly more error-free records (P = .003). CONCLUSIONS: Feasibility outcomes integral to completion of an Internet-based, multisite study were successfully achieved. Further development of programmable electronic safeguards is indicated. The error analysis conducted in this study will aid design of specific field restrictions for electronic CRFs, an important component of clinical trial management systems. PMID- 17341752 TI - Validity of parental reporting of recent episodes of acute otitis media: a Slone Center Office-Based Research (SCOR) Network study. AB - BACKGROUND: The validity of parental reporting of children's health outcomes is an important methodological issue in community-based pediatric research. We assessed the validity of parents' reports of their children's acute otitis media (AOM) history over the previous month in a pilot study of xylitol for AOM prevention. METHODS: Parents of children participating in a study conducted in the Slone Center Office-Based Research (SCOR) Network were interviewed monthly for 3 months and asked whether their child had been diagnosed with AOM in the previous month. A blinded physician reviewed medical records. Results from parental interviews and medical records were compared by correlation analysis. RESULTS: Medical records were obtained for 102 of 120 children (85.0%); 272 monthly interviews were completed. Kappa for the agreement between parental reports and medical records was 0.88 [95% confidence intervals (CI): 0.76 to 0.94]. The positive predictive value of a parental report of an AOM episode within the previous month was 85.0%, and the negative predictive value was 99.1%. CONCLUSIONS: The results of this study suggest that parental reporting of children's recent AOM history correlates well with medical records. Parental interview is a reasonable approach to collecting data on recent AOM outcomes, particularly in large-scale community-based studies where obtaining medical records is often impractical. PMID- 17341753 TI - Cross-sectional comparison of electronic and paper medical records on medication counseling in primary care clinics: a Southern Primary-Care Urban Research Network (SPUR-Net) study. AB - INTRODUCTION: This study compared the frequency of oral counseling and written information by primary care physicians at paper medical record (PMR) clinics and electronic medical record (EMR) clinics, and assessed relationships between medication counseling and medication outcomes (knowledge, questions, reported adherence and side effects, and medication fill). METHODS: A cross-sectional study with two convenience samples of English-speaking adult patients receiving > or =1 prescription at the primary care index visit was conducted in two PMR clinics, with 184 (48% response) patients seen by one of 22 physicians, and in two EMR clinics, with 249 (37% response) patients seen by one of 25 physicians. Data were from medical record reviews of the index visit and 2-week post-visit telephone interviews. RESULTS: Three mutually exclusive counseling categories were evaluated. Patients received 1,095 prescriptions, 61% with oral counseling for indications, 21% with oral counseling for indications and side effects, and 12% with written information plus oral ("multi-mode") counseling. General linear mixed models found 1) less multi-mode counseling in PMR clinics (2%) than EMR clinics (20%); 2) PMR and EMR clinics were similar in oral counseling for indications and side effects; and 3) PMR clinics provided more oral counseling only for indications (69%) than EMR (53%) clinics. The impact of receiving oral or written counseling on patients' reports of having questions about their medications was inconclusive. Not receiving oral counseling for indications was associated with more questions, but not receiving written information was associated with fewer questions. Filling a prescription was lower when no oral counseling for indications and side effects was reported, but the absence of written information was associated with more prescriptions fills. CONCLUSIONS: Physicians' use of EMR to print medication information did not seem to compromise their oral counseling for medication indications and side effects. This feature of the EMR was underutilized by physicians; however, future studies addressing patient recall and evaluating the quality and content of medication counseling are needed. PMID- 17341754 TI - Practice-based assessment of tobacco usage in southwestern primary care patients: a Research Involving Outpatient Settings Network (RIOS Net) study. AB - PURPOSE: Primary care clinicians rely, perhaps erroneously, on general population based data about risk factors to help form their strategies for allocating time in the brief primary care encounter. We conducted a case study using rates of tobacco usage among people presenting for primary care to explore comparability to general population-based rates. METHODS: Clinicians in RIOS Net, a practice based research network, gathered data on tobacco use for all patients presenting during a 2-week period. We compared those data to population-based data by gender and ethnicity. RESULTS: Ninety-one primary care clinicians reported data on 2442 patients. Primary care smoking rates differed in important ways from general population-based rates. Hispanic women smoked at more than twice the national population-based rate (25% vs 12%). Youth smoked at higher rates as well, particularly young Native American men. CONCLUSIONS: Patients seen in primary care differ in important ways in rates and patterns of tobacco usage when compared with rates reported in population-based surveys. These differences could have important implications for preventive care within the context of multiple competing demands in the primary care encounter. PMID- 17341755 TI - The IRB challenge for practice-based research: strategies of the American Academy of Family Physicians National Research Network (AAFP NRN). AB - Investigators for multisite research studies conducted in practice-based research networks face numerous challenges associated with Institutional Review Boards (IRBs) and human subjects protection. The American Academy of Family Physicians National Research Network (AAFP NRN) has adopted strategies to deal with some of these challenges, including creating an open, honest relationship with the new American Academy of Family Physicians Institutional Review Board (AAFP IRB); creating procedures for members who are not required to report to a local IRB; handling most of the IRB application submission and tracking tasks for our members who must submit applications to local IRBs; and working with the AAFP IRB to make required human subjects training relevant to our practices. However, these are only temporary solutions. It is time to begin working toward a permanent solution. As such, the AAFP, the AAFP NRN, and the AAFP IRB have begun discussing the possibility of adopting an alternative model of central IRB review, which would facilitate practice-based research in family medicine and which would encourage rather than discourage family medicine practices to participate in research studies that will further the discipline. PMID- 17341756 TI - The role of health information technology in the translation of research into practice: an Oklahoma Physicians Resource/Research Network (OKPRN) study. AB - Implementation of health information technology (HIT) has become a cornerstone of efforts to improve patient care in primary care practices. However, relatively few publications have explored the impact of HIT on the need for fundamental changes in the primary care delivery process. There is also very little published information about how HIT implementations can drive translation of research findings into practice in primary care. This article describes the process of developing and implementing the Preventive Services Reminder System in the Oklahoma Physicians Resource/Research Network, a practice-based research network, and demonstrates how strategic adoption of HIT led to the re-engineering of practices and to subsequent improvements in delivery of evidence-based preventive services. PMID- 17341757 TI - Information technology in PBRNs: the Indiana University Medical Group Research Network (IUMG ResNet) experience. AB - OBJECTIVE: Research in practice-based research networks (PBRNs) is hampered by difficulty managing, identifying, and enrolling potential subjects. Well-designed informatics applications can greatly improve these processes. METHODS: We considered a literature review, discussion with PBRN researchers, and personal experience to outline important principles to apply when considering electronic data collection in a PBRN. We provide specific working examples of electronic means we use to improve data collection and patient enrollment. RESULTS: Our PBRN has screened more than 18,000 patients and enrolled more than 6000 study subjects in 5 years. Less than 2% of potentially eligible patients are missed by our research assistants. We achieved this high rate of success through extensive integration of the ResNet infrastructure (research databases and personnel) with an electronic medical record (EMR) system and computerized provider order entry. We make extensive use of widely used standards for data storage, definition, and transmission to ensure data reusability. We successfully implemented a real-time means to identify follow-up patients. CONCLUSION: Electronic data collection can greatly facilitate PBRN research, particularly by improving data management and identification of eligible patients. Key principles to ensure successful implementation include use of data standards and centralized electronic data management. PMID- 17341758 TI - Characterizing a practice-based research network: Oregon Rural Practice-Based Research Network (ORPRN) survey tools. AB - OBJECTIVE: To present the survey methods and instruments used to characterize a geographically and professionally diverse rural practice-based research network (PBRN). METHODS: A cross-sectional study of Oregon PBRN (ORPRN) member practices and clinicians using a 3-part survey including a survey of the practices, of clinician members, and an anonymous survey of clinician satisfaction. RESULTS: A total of 31 of 32 (97%) participating ORPRN practices completed the practice survey, 96 of 129 (74%) clinicians within these practices completed the clinician member survey, and 81 of 129 (63%) clinicians completed an anonymous survey of clinician satisfaction. The survey provided a detailed description of the structure of member practices, patient and clinician demographics, services provided by the practices, and access to specialty and ancillary services. CONCLUSIONS: Survey tools that describe the network practices and individual clinician characteristics contribute to an understanding of the research capacity of an individual PBRN. PMID- 17341759 TI - Strategies for planning and launching PBRN research studies: a project of the Academy of Family Physicians National Research Network (AAFP NRN). AB - Research conducted in a practice-based research network (PBRN) differs from other multisite research and presents particular planning challenges. The American Academy of Family Physicians National Research Network (AAFP NRN) has developed a number of procedures used for planning and implementing studies, which address the challenges of national PBRN studies. In this study, we highlight challenges common to PBRN research and describe the methods used by the AAFP NRN to address those challenges. The following tasks were identified as important to implementing PBRN research studies: (1) selecting fundable, feasible studies that interest members and have the potential to improve quality of care; (2) creating a practical budget that covers the costs of the study; (3) composing study teams and securing written agreements between team members; (4) recruiting and selecting study sites; and (5) training practice staff and physicians. Striking the balance of scientific rigor with practical application of PBRN studies must be addressed throughout these tasks. Proper planning for PBRN studies significantly affects the success of study implementation. Although developed by a national PBRN, the planning procedures described in this study may be adapted for state or regional PBRNs. PMID- 17341760 TI - National Institutes of Health eliminates funding for national architecture linking primary care research. AB - With the ending of the National Electronic Clinical Trial and Research Network (NECTAR) pilot programs and the abridgement of Clinical Research Associate initiative, the National Institutes of Health Roadmap presents a strategic shift for practice-based research networks from direct funding of a harmonized national infrastructure of cooperating research networks to a model of local engagement of primary care clinics performing practice-based research under the aegis of regional academic health centers through Clinical and Translational Science Awards. Although this may present important opportunities for partnering between community practices and large health centers, for primary care researchers, the promise of a transformational change that brings a unified national primary care community into the clinical research enterprise seems likely to remain unfulfilled. PMID- 17341764 TI - Regulation of ciliary beat frequency in airways: shear stress, ATP action, and its modulation. PMID- 17341765 TI - Surfactant dysfunction and lung injury due to the E. coli virulence factor hemolysin in a rat pneumonia model. AB - This study tests the hypothesis that the virulence factor hemolysin (Hly) expressed by extraintestinal pathogenic Escherichia coli contributes to surfactant dysfunction and lung injury in a rat model of gram-negative pneumonia. Rats were instilled intratracheally with CP9 (wild type, Hly-positive), CP9hlyA (Hly-minus), CP9/pEK50 (supraphysiological Hly), or purified LPS. At 6 h postinfection, rats given CP9 had a decreased percentage content of large surfactant aggregates in cell-free bronchoalveolar lavage (BAL), decreased large aggregate surface activity, decreased Pa(O2)/FiO2) ratio, increased BAL albumin/protein levels, and increased histological evidence of lung injury compared with rats given CP9hlyA or LPS. In addition, rats given CP9/pEK50 or CP9 had decreased large aggregate surface activity, decreased Pa(O2)/FiO2) ratios, and increased BAL albumin/protein levels at 2 h postinfection compared with rats given CP9hlyA. The severity of permeability lung injury based on albumin/protein levels in BAL at 2 h was ordered as CP9/pEK50 > CP9 > CP9hlyA > normal saline controls. Total lung titers of bacteria were increased at 6 h in rats given CP9 vs. CP9hlyA, but bacterial titers were not significantly different at 2 h, indicating that increased surfactant dysfunction and lung injury were associated with Hly as opposed to bacterial numbers per se. Further studies in vitro showed that CP9 could directly lyse transformed pulmonary epithelial cells (H441 cells) but that indirect lysis of H441 cells secondary to Hly-induced neutrophil lysis did not occur. Together, these data demonstrate that Hly is an important direct mediator of surfactant dysfunction and lung injury in gram-negative pneumonia. PMID- 17341766 TI - MR spectroscopy, functional MRI, and diffusion-tensor imaging in the aging brain: a conceptual review. AB - In vivo magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), and diffusion-tensor imaging (DTI) have recently opened new possibilities for noninvasively assessing the metabolic, functional, and connectivity correlates of aging in research and clinical settings. The purpose of this article is to provide a conceptual review intended for a multidisciplinary audience, covering physical principles and main findings related to normal aging and senile cognitive impairment. This article is divided into 3 sections, dedicated to MRS, to fMRI, and to DTI. The spectroscopy section surveys physiological function of the observable metabolites, concentration changes in normal aging and their interpretation, and correlation with cognitive performance. The functional MRI section surveys the hemispheric asymmetry reduction model from compensation and de-differentiation viewpoints, memory encoding, retrieval and consolidation, inhibitory control, perception and action, resting-state networks, and functional deactivations. The DTI section surveys age related changes, correlation with behavioral scores, and transition to cognitive impairment. PMID- 17341767 TI - Validity of the Cambridge Cognitive Examination-Revised new Executive Function Scores in the diagnosis of dementia: some early findings. AB - The Cambridge Cognitive Examination-Revised introduces 2 new executive items (Ideational Fluency and Visual Reasoning), which separately or combined with 2 executive items in the former version (word list generation and similarities) might constitute an Executive Function Score (EFS). The authors studied the validity of these new EFSs in 51 demented (dementia of the Alzheimer's type, vascular dementia) and nondemented individuals (depressives and normals). The new EFSs were found valid to accurately differentiate between demented and nondemented subjects; however, they were considerably less so when specific diagnoses were considered. Correlations between the variously combined executive scores and the cognitive scales and subscales studied were prevalently low to moderate, and ranged from high and significant to low and nonsignificant when the 4 executive items were correlated to each other. The ability of the executive scores to discriminate demented from nondemented individuals was lower compared with the Cambridge Cognitive Examination-Revised scores. EFS was found internally consistent. PMID- 17341768 TI - Early-onset Alzheimer's disease is associated with greater pathologic burden. AB - Two subtypes of Alzheimer's disease (AD) have been commonly identified: early- and late-onset forms. Previous studies suggest that early-onset AD patients have more neuritic plaques (NPs) and neurofibrillary tangles (NFTs). In the current study, NP and NFT counts were performed for 8 brain regions in 25 subjects with definite AD. A repeated-measures analysis of variance of mean regional NP and NFT counts for early- and late-onset groups was performed. A significant between subject effect indicating greater overall NP and NFT burden in the early-onset group was observed (NP: F = 6.8, df = 1, P = .015; NFT: F = 7.5, df = 1, P = .012). This analysis supports the hypothesis that early-onset AD is associated with greater pathologic burden than late-onset AD. This suggests that late-onset AD patients have less cognitive reserve than early-onset patients and require fewer pathologic changes to exhibit cognitive deterioration. PMID- 17341769 TI - Confabulations in episodic memory are associated with delusions in Alzheimer's disease. AB - Although confabulations and delusions are observed in Alzheimer's disease, the relationship between the 2 has not been fully investigated. This study involved 50 patients with Alzheimer's disease and 10 healthy participants. After the patients were divided into delusional and nondelusional groups, confabulations and cognitive function were assessed. No confabulations appeared in the healthy participants, and only patients with Alzheimer's disease showed confabulations. The delusional group produced more confabulations on episodic subjects than on semantic subjects. There was a correlation between cognitive impairment and confabulations in semantic memory. These findings suggest that different mechanisms are involved in confabulations between semantic and episodic memories. PMID- 17341770 TI - Prevalence and predictors of neuropsychiatric symptoms in cognitively impaired nursing home patients. AB - The prevalence of neuropsychiatric symptoms and the influence of predictive factors in cognitively impaired nursing home patients were reviewed. Articles were identified by means of a MEDLINE and PsychInfo literature search. Neuropsychiatric symptoms were present in more than 80% of the cognitively impaired patients. Prevalences ranged considerably, from 3% to 54% for delusions, 1% to 39% for hallucinations, 8% to 74% for depressed mood, 7% to 69% for anxiety, 17% to 84% for apathy, 48% to 82% for aggression or agitation, and 11% to 44% for physical aggression. Neuropsychiatric symptoms seemed to be predicted not only by dementia type or stage but also by the psychosocial environment and the amount of psychoactive medication and physical restraints used. Neuropsychiatric symptoms are common and influenced by both the disease itself and the psychosocial environment of the institutional setting. The latter may have important consequences for staff planning and education and the future design of care facilities. PMID- 17341771 TI - Clinical diagnosis of dementia, not presence of behavioral and psychological symptoms, is associated with psychotropic use in community-dwelling elders classified as having dementia. AB - Little is known about the prevalence and correlates of psychotropic use in community-dwelling elders with dementia. Baseline data from 285 community dwelling elders with a research classification of dementia (based on a neuropsychological battery of 4 tests) and their knowledgeable informants enrolled in the observational Memory and Medical Care Study were analyzed. A total of 33.3% of subjects with a research classification of dementia were clinically diagnosed, 28.8% used at least 1 psychotropic drug, and 61.8% had at least 1 behavioral or psychological symptom of dementia (BPSD). Presence of BPSD was associated with a higher likelihood of a clinical diagnosis of dementia. Multivariate logistic regression showed a clinical diagnosis of dementia, not BPSD, was associated with psychotropic use; clinical recognition of dementia appears to be an intermediate step between presence of BPSD and prescription of psychotropics. In addition, most community-dwelling elders meeting the research criteria for dementia were not clinically diagnosed, despite contact with a physician (89%) in the previous year. PMID- 17341772 TI - Effect of divided attention on gait in subjects with and without cognitive impairment. AB - The aim of this study was to investigate the influence of cognition on motor function using 2 simple everyday tasks, talking and walking, in younger subjects with Alzheimer's disease and mild cognitive impairment. A second aim was to evaluate reliability for the dual-task test Talking While Walking. Walking speed during single and dual task and time change between single and dual task were compared between groups. The test procedure was repeated after 1 week. Subjects with AD had lower walking speed and greater time change between single and dual task compared with healthy controls. Reliability for Talking While Walking was very good. The results show that motor function in combination with a cognitive task, as well as motor function alone, influences subjects with Alzheimer's disease in a negative way and that decreased walking speed during single- and dual-task performance may be an early symptom in Alzheimer's disease. PMID- 17341773 TI - Provisional T-drug-eluting stenting technique for the treatment of bifurcation lesions: clinical, myocardial scintigraphy and (late) coronary angiographic results. AB - BACKGROUND: Treatment of bifurcation stenoses (BS) by percutaneous coronary intervention (PCI) remains challenging, even with drug-eluting stents (DES). We aimed to appraise clinical, myocardial scintigraphy and late (>9 months) exploratory angiographic outcomes of provisional T-stenting in the management of BS. METHODS: We enrolled 53 consecutive patients with BS in the proximity of a greater than or equal to 2 mm side branch (SB). The provisional T-technique was performed in all cases, with implantation of DES in the main branch (MB), SB balloon-only dilatation, and final kissing in the event of >50% SB stenosis. Provisional SB-stenting (using another DES) was reserved to cases with persisting >50% stenosis/dissection and reduced TIMI flow. Further kissing inflation was recommended in such patients. Stress/rest single-photon emission computed tomography (MIBI) and coronary angiography follow up were scheduled >6 and 9 months after PCI, respectively. RESULTS: Major adverse cardiac events at 14 +/- 3 months occurred in 5 patients (9.4% [95% confidence interval 0.1-17.4%]: 1 (1.9% [0.1-5.8%]) non-Q-wave myocardial infarction for subacute stent thrombosis, 2 (3.8% [0.1-9.0%]) target lesion revascularizations and 2 (3.8% [0.1-9.0%]) target vessel revascularizations. Six-month MIBI was performed in 51 patients (96.3%): 4 patients had positive results (7.8% [0.2-15.4%]). Angiography was performed in 4 of these patients and in another 27 patients, with clinical restenosis occurring overall in only 5 (16.1% [8.9-23.3%]), 1 case of clinical restenosis in the MB (3.2% [0.6-9.4%]), and 4 in the SB (12.9% [5.1-24.9%]). CONCLUSIONS: This study suggests the safety and efficacy of provisional T-drug-eluting stent implantation in bifurcation coronary lesions, and supports the use of follow-up myocardial scintigraphy, with angiography reserved for selected patients and lesions. PMID- 17341774 TI - Provisional side branch stenting: a justified approach in the era of drug-eluting stents. PMID- 17341775 TI - The angiographic step-up and step-down: a surrogate for optimal stent expansion by intravascular ultrasound. AB - BACKGROUND: Standard high-pressure stent implantation frequently results in suboptimal stent expansion by intravascular ultrasound (IVUS) criteria. We aim to show that routine expansion of the stent to a diameter greater than the reference segment, leading to an angiographic step-up at the proximal stent edge and step down at the distal stent edge, results in improved stent expansion. METHODS: We studied 25 patients undergoing coronary stent implantation. Twelve patients were randomized to standard sizing and 13 patients to step-up and step-down sizing as the angiographic goal. IVUS was then performed on all patients to detect incomplete stent strut apposition, dissection within the stent or a suboptimal stent expansion index (SEI). SEI was defined as the minimum stent area (MSA)/average reference lumen area x 100. Optimal SEI was defined as greater than or equal to 90% for a MSA less than or equal to 9.0 mm2 and greater than or equal to 80% for a MSA >9.0 mm2. RESULTS: Four patients (33%) treated with standard stent implantation and 12 patients (92%) treated with the step-up and step-down approach (p = 0.004) achieved optimal stent expansion. No patients in either group had unapposed stent struts or instent dissection on IVUS. There were no major adverse cardiac events on 6-month follow up. CONCLUSIONS: Stent deployment with an angiographic step-up and step-down approach improves the likelihood of optimal stent deployment by IVUS criteria as compared to the standard angiographic endpoint. This stenting technique is a simple and frugal alternative to IVUS-guided percutaneous coronary intervention, achieving very high rates of adequate stent apposition and expansion. PMID- 17341776 TI - Optimal stent expansion: is the eye of the beholder as good as intravascular ultrasound. PMID- 17341777 TI - Examination of anti-intima hyperplastic effect on cilostazol-eluting stent in a porcine model. AB - BACKGROUND: Current drug-eluting stents (DES) have shown a reduction in neointimal hyperplasia and restenosis. However, the aggressive use of DES has an untoward side effect known as DES thrombosis. To overcome this unfavorable effect, other drug candidates are currently being studied. Cilostazol is known to inhibit intimal proliferation and accelerate endothelialization. These beneficial properties suggest that the drug could be a DES candidate. METHODS: Twelve juvenile swine were randomly assigned to two groups receiving either cilostazol eluting stents (CES) or bare-metal stents (BMS). All except 1 in the BMS group received follow-up angiography and were sacrificed at day-28 for histopathological analysis. RESULTS: A similar inflammatory response to stenting was observed in both groups on histopathological analysis. No significant difference was observed in the injury score between the groups, suggesting that the drug and PEA polymer were not associated with inflammation. There was a 23% reduction in intimal area in the CES group compared with the BMS group (1.58 +/- 0.8 mm2 vs. 2.05 +/- 0.82 mm2 for cilostazol vs. bare metal, respectively; p = 0.04). Late loss was also significantly lower in the CES group than in the BMS group (0.82 +/- 0.81 mm vs. 1.86 +/- 1.04 mm, respectively; p = 0.0296). CONCLUSION: The present study demonstrated that CES suppressed intimal hyperplasia and reduced intimal late loss. Pleiotropic effects of cilostazol such as the suppression of restenosis and the acceleration of endothelialization demonstrated in systemic delivery can also be expected in local delivery. PMID- 17341778 TI - A hand-held device to measure oxygen uptake: performance characteristics, patient selection and the propagation of its measurement error into fick cardiac output determinations. AB - Measured oxygen consumption rates (VO2) are being used less frequently for direct Fick cardiac output determinations during cardiac catheterization because the instruments that measure VO2 are usually cumbersome, expensive and difficult to use. A small, inexpensive VO2 device recently became available. Therefore, the aims of this report are: (1) to delineate the advantages and limitations that would affect its use during cardiac catheterization; (2) to define the patient population in which its use would be safe and effective; and (3) to estimate the accuracy of cardiac output determinations based on its VO2 measurements. The MedGem is a fist-size device that measures VO2 as a patient breathes through it using either a facemask or mouthpiece. We evaluated it by measuring the external deadspace it imposes on the patient, by measuring the time required for each measurement, by determining its precision from repeated measurements on healthy volunteers and animals, and by developing a statistical model that calculates cardiac output error as a function of the random errors in the measurements of arterial and venous oxygen concentrations and VO2. Our experience indicates the MedGem is easy to operate and can be used for a wide spectrum of patients at rest including children with the ventilatory capacity to compensate for the added deadspace. Cardiac output determinations made with the MedGem's measurements of oxygen uptake are clinically acceptable if the oximeter used to measure oxygen in arterial and mixed venous blood is also sufficiently accurate. Our statistical model illustrates strategies to minimize cardiac output error. PMID- 17341779 TI - Impact of gender on in-hospital percutaneous coronary interventional outcomes in African-Americans. AB - BACKGROUND: Previous studies on outcomes following percutaneous coronary intervention (PCI) have shown an increased rate of in-hospital mortality and vascular complications in women compared to men. The impact of gender on post-PCI outcomes in African-Americans has not been reported. METHODS: We retrospectively analyzed 835 consecutive African-American patients (n = 392 men and n = 443 women) who underwent PCI using a glycoprotein IIb/IIIa inhibitor (GPI) bolus-only strategy from January 2003 to August 2004 at a single institution. Baseline characteristics, procedural data, and in-hospital outcomes were recorded. RESULTS: Women were older and had a higher mean body mass index (BMI) compared to men. Men were more likely to be smokers, more often had triplevessel disease and left ventricular dysfunction compared to women. There were no deaths or repeat revascularizations in either group. After adjustment for baseline risk factors and procedural characteristics, there was no significant difference in the composite endpoint of in-hospital death, myocardial infarction (MI), and repeat revascularization between men and women (6.38% in men and 2.48% in women; p = 0.051), but women had a higher rate of major and minor bleeding (0.5 vs. 2.5; p = 0.019; and 0.5 vs. 2.3; p = 0.021, respectively). On multiple logistic regression analysis, female gender was an independent risk factor for bleeding post-PCI (adjusted odds ratio [OR]-5.6, 95% confidence intervals [CI]: 1.15-27.45). CONCLUSION: Although there is no difference in the in-hospital composite endpoint of death, MI, and repeat revascularization, African-American women are at increased risk for bleeding complications post-PCI, even when a GPI bolus-only strategy is used. PMID- 17341780 TI - PCI in African-American women: closing the gender gap. PMID- 17341781 TI - Limitations of using a GuardWire temporary occlusion and aspiration system in patients with acute myocardial infarction: multicenter investigation of coronary artery protection with a distal occlusion device in acute myocardial infarction (MICADO). AB - BACKGROUND: The benefits of using distal protection during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) remain unknown. The prevention of no-reflow in PCI is considered a challenge and could be a contributing factor for long-term prognosis. OBJECTIVES: This study evaluated the efficacy of distal protection with the GuardWire distal protection device in PCI at the time of AMI revascularization. METHODS: The study was conducted as a prospective, randomized, multicenter trial. Patients with AMI within 24 hours from onset were randomized into either PCI combined with a GuardWire, or PCI without distal protection. The primary endpoints were TIMI perfusion grade (TMP) and no incidence of reflow. Secondary endpoints were major cardiac events (MACE) during 6-month follow up. RESULTS: The incidence of no-reflow was similar between the GuardWire group and the control group (4% vs. 3%). TMP 3 was seen at a higher rate in the GuardWire group, but was not statistically significant (58% vs. 44%; p = 0.054). Multivariate analysis revealed that diabetes and hyperlipidemia, but not GuardWire use, were predictors of failure to achieve TMP 3. Older age and right coronary artery (RCA) infarction were associated with achieving TMP 3. MACE was observed in similar incidences between the two groups after 6-month follow up. CONCLUSIONS: From our randomized study of distal protection in PCI at the time of AMI, elderly patients or those with RCA infarction were considered good candidates for distal protection; however, we could not demonstrate an improvement in long-term outcome with the use of GuardWire distal protection. PMID- 17341782 TI - Ruptured giant right coronary artery aneurysm percutaneously plugged. AB - The endovascular management of a patient with a ruptured giant coronary aneurysm presenting with chest pain followed by anterior chest wall ecchymosis and shock is described. The inflow to a large, acutely leaking right coronary aneurysm was successfully sealed with the Amplatzer Vascular Plug device. The patient was estimated to be at very high risk for surgical intervention. The use of this device to seal an acutely leaking coronary aneurysm has not been previously described. PMID- 17341783 TI - Preliminary experiences closing secundum atrial septal defect using the modified Cardia Intrasept device. AB - During the past decade, transcatheter occlusion of secundum atrial septal defects (Type II ASDs) has become a widely accepted alternative to surgical closure. To date, over 6,000 patients have been treated with the Cardia Intrasept PFO occluder (Cardia Inc., Burnsville, Minnesota) for the percutaneous closure of patent foramen ovale (PFO). This is a report of the use of a modified Intrasept device to close Type II ASDs in 4 patients. PMID- 17341784 TI - In-stent pseudo-restenosis due to an organized thrombus six months after implantation of a sirolimus-eluting stent. AB - Restenosis after sirolimuseluting stent (SES) implantation has been reported to be usually focal. We report a case of focal in-stent stenosis discovered angiographically 6 months after SES implantation, despite continuation of dual antiplatelet medication. Continuity and uniform distribution of the struts were confirmed by intravascular ultrasound (IVUS). Material from the lesion was extracted and found to be an organized thrombus on histological inspection. This observation suggests that special attention should be paid to focal stenotic lesions, particularly when IVUS shows proper and circular stent expansion, since it might represent an atypical form of late stent thrombosis. PMID- 17341785 TI - Sirolimus-eluting stent implantation outside a previous stent. AB - With device improvements, more total occlusions have been crossed with a guidewire and balloon. However, true intraluminal/intrastent passage is not always accessed, which is not apparent on coronary angiography. In this study, using intravascular ultrasound as well as computed tomography, we demonstrated a crushed stent previously implanted outside the sirolimus-eluting stent, which resulted from subintimal (outside the stent) passage of a guidewire. PMID- 17341787 TI - The Radi PressureWire thermistor for intracoronary thermography. PMID- 17341788 TI - Successful percutaneous interventions with limited crossing of the penetration catheter into severe coronary artery stenoses. AB - The novel Tornus penetration catheter, which has recently been approved by the FDA, is designed to cross difficult coronary lesion types such as chronic total occlusions. Published case studies on the Tornus have all demonstrated successful lesion crossing by the penetration catheter, thereby allowing for optional guidewire exchange and successful procedural outcomes. In the present two case reports, the penetration catheter demonstrates its effectiveness in the necessary guidewire exchange for rotational atherectomy without fully crossing the coronary lesions. In advanced coronary stenoses such as those with chronic total occlusions, severely stenotic, heavily calcified, long, diffuse lesions, the ability to perform guidewire exchange with only limited or partial lesion penetration with the Tornus device is invaluable. This facet of the penetration catheter adds to the overall armamentarium of options in the percutaneous treatment of advanced coronary artery stenoses. PMID- 17341789 TI - Global akinesis: inadvertent left ventricular "pseudoaneurysmogram". AB - With today's widespread use of thrombolytic therapy and primary coronary intervention, left ventricular (LV) pseudoaneurysms (PA) are now uncommon sequela of myocardial infarction. Nonetheless, when encountered, the decision of surgical versus medical therapy is not always clear. We present a patient who developed a massive postinfarct PA, likely due to refusal of therapy. The LV was initially believed to be globally akinetic on catheterization. Subsequent review revealed, however, that the left ventriculogram was, in reality, a psuedoaneurysmogram. The recommendation for surgical intervention in this patient was prompted by the need for coronary bypass as well as mitral valve repair. PMID- 17341790 TI - The parallel wire technique to deal with wire-induced dissection of a complex calcified lesion. AB - Coronary dissection is not an uncommon phenomenon during coronary angioplasty. Coronary dissection can occur due to a variety of interventions, including balloon inflation, atherectomy, stent edge dissections, guide catheter trauma and wire-induced dissections, to name a few. Once a severe dissection has occurred, it is often challenging to find the true lumen. The parallel wire technique has been described in the literature for the recanalization of chronic total occlusions and also to recanalize guide catheter-induced spiral dissections of the right coronary artery. We report a novel case of an extensive wire-induced dissection of a calcific and tortuous right coronary artery, which was recanalized using the parallel wire technique. PMID- 17341791 TI - Covered stent implantation for the treatment of an aneurysm involving a coronary bifurcation. AB - We report the percutaneous treatment of an aneurysm of the mid-segment of the left anterior descending artery involving a bifurcation with a diagonal branch in a patient with three-vessel disease. Due to the nonavailability of a dedicated device, we used a V-configured bifurcation system consisting of a polytetrafluoroethylene-covered stent for the main vessel and a baremetal stent for the side branch. The angiographic result was optimal and the patient remained symptom-free at 1-year follow up when the stress test was negative. The follow-up coronary angiography showed no restenosis of the coronary segments treated by stent implantation. PMID- 17341792 TI - Thrombus aspiration and local fibrinolytic therapy for acute pulmonary thromboembolism. PMID- 17341793 TI - A rare case of anomalous left anterior descending artery with a large interarterial communication: an invasive and CT angiographic study. AB - Recent advances in computed tomography (CT) technology have made this technique useful in evaluating coronary anatomy. Although CT has been the method of choice to evaluate vascular anatomy of the thorax for many years, the coronary arteries, until recently, could not be imaged with diagnostic quality due to cardiac and respiratory motion. The improved temporal and spatial resolution of new generation multirow detector scanners makes noninvasive evaluation of the coronary arteries possible. Magnetic resonance imaging (MRI) has been the noninvasive method of choice to evaluate proximal coronary anatomy, but is not available in many centers. CT angiography (CTA) is more readily available, has better spatial resolution than MRI, and is quickly becoming an alternate method to evaluate the coronary arteries. Cardiac catheterization is the gold standard in imaging normal and abnormal coronary arteries, but even this technique has limitations. It is occasionally difficult to delineate the course of anomalous vessels, particularly if the anomalous vessel courses between the aorta and pulmonary artery, or if it has an intramyocardial course. We describe a patient with this type of abnormal coronary anatomy in whom CTA supplemented the invasive angiogram. PMID- 17341794 TI - Recanalization of an occluded right coronary artery into the right internal mammary artery using a retrograde approach. AB - Recanalization of chronic total occlusions (CTO) remains one of the most technically challenging areas in interventional cardiology. We report a case of retrograde recanalization of a chronically occluded mid-right coronary artery into a right internal mammary graft via a septal collateral. This retrograde approach provides another option for CTO recanalization when the anterograde approach has failed. PMID- 17341795 TI - [Patient safety in Iceland]. PMID- 17341796 TI - [Alcohol policy in Iceland]. PMID- 17341798 TI - [Health promotion in day-care centres in Reykjavik--intervention and result of actions]. AB - OBJECTIVE: The purpose of the study was to compare wellbeing, health and work environment before and after intervention among employees of Reykjavik city day care centre. MATERIAL AND METHODS: The study is a prospective interventions study. In the year 2000 employees of 16 day-care centres responded to a questionnaire regarding work environment, health and wellbeing. Work environment evaluation was completed and the centre classified into four groups accordingly. Subsequently, the "equipment was renewed" noise protection improved and the employee received education concerning occupational health. Six months, after interventions, in the year 2002 the same questionnaire was readministered. RESULTS: Response rate in 2002 was 88% (n=267) but 90% in the year 2000. Work environment had improved. More employees had received instruction on good workposture and good work technique than 2 years earlier. Fewer employees used awkward posture than before. Better workspace resulted in reduced number of symptoms, also for the youngest employees. Symptoms were also fewer where unskilled employees were in majority and where the fewest of them had received proper education on work posture. In the year 2002, psychosocial wellbeing was better or equal than two years earlier. This was associated with better education and higher age even despite less workspace. Employees awareness towards noise was greatly improved. CONCLUSION: It is possible to improve work methods and work environment of employees with goal directed intervention, thus laying the ground for wellbeing at work. The interplay between the factors education and age is complex, though. Thus it is important, that all workplaces, adopt the process of "risk assessment", intervention, and then reassessment of the work environment. By doing so the goals of health promotion and good occupational health can be reached. PMID- 17341797 TI - [The role of alcohol consumption in adolescent emergency room visits at Landspitali University Hospital, Iceland]. AB - OBJECTIVE: The records of the emergency room of Landspitali University Hospital in Iceland provide important information on the prevalence and incidence of various problems. The objective of this research is to evaluate the reliability of data concerning the visits of adolescents under the influence of alcohol. DATA AND METHODS: Records of visits to the Emergency Room of Landspitali University Hospital by 14-16 year old capital region adolescents are compared with the results of a survey in early 2003. The correspondence between hospital records and adolescent self-reports is compared to the correspondence between records and self-reports of the presence of alcohol in visits. RESULTS: In all cases students report more emergency room visits than are recorded by Landspitali University Hospital. The difference is 4.2% (+/- 0.6%) in accident visits and 2.2% (+/- 0.2%) in violence visits. In the case of the presence of alcohol in visits the difference is 9.3% (+/- 0.4%) between hospital records (0.2%) and adolescent self reports (9.5%). CONCLUSION: The records of Landspitali University Hospital are not a valid source of information on alcohol-related problems among adolescents. About one in ten adolescents in the capital region of Iceland claim to have visited an emergency room because of their own alcohol consumption but hospital records of the presence of alcohol only include about 1/60 of that number. PMID- 17341799 TI - [Advances in detection, evaluation and management of chronic kidney disease]. AB - The incidence of end-stage kidney failure has increased dramatically world-wide in recent decades. It is a disorder that carries high mortality and morbidity and its treatment is expensive. Increased emphasis has been placed on early detection in recent years in the hope that it may lead to preventive strategies. However, these efforts have been hampered by ambiguous disease definitions. Recent guidelines have defined chronic kidney disease (CKD) as glomerular filtration rate (GFR) less than 60 ml/min/1.73 m(2) and/or evidence of kidney damage by laboratory or imaging studies, of more than 3 months duration. Chronic kidney disease is divided into 5 stages based on renal function, where stage 1 is defined as normal GFR or above 90 ml/min/1.73 m(2), and stage 5 as GFR below 15 ml/min/1.73 m(2) which is consistent with end-stage kidney failure. The GFR can be measured directly but more conveniently it is calculated based on serum creatinine using formulas that have been shown to be fairly accurate. Epidemiological studies employing the new definition have shown that the prevalence of CKD is 5-10% in Western countries, leading to its recognition as a major public health problem. It has also been demonstrated that CKD is associated with increased cardiovascular risk. This year the Clinical Biochemistry Laboratory at Landspitali University Hospital will begin reporting the estimated GFR along with the serum creatinine values. It is important that Icelandic physicians learn to use the estimated GFR in their daily practice to make the diagnosis and staging of CKD more effective. Hopefully this will lead to earlier detection and institution of therapy that may retard the development of end-stage kidney failure and decrease the associated cardiovascular risk. PMID- 17341800 TI - The polonium-210 poisoning in London. PMID- 17341801 TI - Evolution over the past century of quantities and units in radiation dosimetry. AB - Following the discovery of x-rays in November 1895, of radioactivity in February 1896 and of radium in December 1898 a large number of proposals were made for x ray units and for radium units. These were based on various radiation effects, including blackening of photographic film, chemical effects, fluorescence and skin erythema. Some were also based on the ionisation effect, and it was this effect which eventually, in 1937, became the basis for all future radiological units of measurement, without any differentiation between x-rays and radium gamma rays. During this period the International Commission on Radiation Units and Measurement (ICRU) and the International Commission on Radiological Protection (ICRP) were set up by the International Congress of Radiology (ICR), as well as some national committees on this topic. This led to a series of reports in respect of (1) fundamental quantities and units for general use produced by the ICRU and (2) quantities and units for use in radiation protection produced by the ICRU and ICRP. In regard to the latter series, alternating contributions from the two commissions were made over the years, but these have resulted in a dual approach to the subject: (a) the ICRP's mean-value quantities for dose-limitation purposes and (b) the ICRU's point-value quantities for measurement purposes, with conversion factors between them. This review summarises this historical evolution over the past century. PMID- 17341802 TI - Polonium-210 as a poison. AB - The death of Alexander Litvinenko on 23 November 2006 has brought into focus scientific judgements concerning the radiotoxicity of polonium-210 ((210)Po). This paper does not consider the specific radiological circumstances surrounding the tragic death of Mr Litvinenko; rather, it provides an evaluation of published human and animal data and models developed for the estimation of alpha radiation doses from (210)Po and the induction of potentially fatal damage to different organs and tissues. Although uncertainties have not been addressed comprehensively, the reliability of key assumptions is considered. Concentrating on the possibility of intake by ingestion, the use of biokinetic and dosimetric models to estimate organ and tissue doses from (210)Po is examined and model predictions of the time-course of dose delivery are illustrated. Estimates are made of doses required to cause fatal damage, taking account of the possible effects of dose protraction and the relative biological effectiveness (RBE) of alpha particles compared to gamma and x-rays. Comparison of LD(50) values (dose to cause death for 50% of people) for different tissues with the possible accumulation of dose to these tissues suggests that bone marrow failure is likely to be an important component of multiple contributory causes of death occurring within a few weeks of an intake by ingestion. Animal data on the effects of (210)Po provide good confirmatory evidence of intakes and doses required to cause death within about 3 weeks. The conclusion is reached that 0.1-0.3 GBq or more absorbed to blood of an adult male is likely to be fatal within 1 month. This corresponds to ingestion of 1-3 GBq or more, assuming 10% absorption to blood. Well-characterised reductions in white cell counts would be observed. Bone marrow failure is likely to be compounded by damage caused by higher doses to other organs, including kidneys and liver. Even if the bone marrow could be rescued, damage to other organs can be expected to prove fatal. PMID- 17341803 TI - Investigation of the sources of residential power frequency magnetic field exposure in the UK Childhood Cancer Study. AB - There is an unexplained association between exposure to the magnetic fields arising from the supply and use of electricity, and increase in risk of childhood leukaemia. The UK Childhood Cancer Study (UKCCS) provides a large and unique source of information on residential magnetic field exposure in the UK. The purpose of this supplementary study was to investigate a sample of UKCCS homes in order to identify the particular sources that contribute to elevated time averaged exposure. In all, 196 homes have been investigated, 102 with exposures estimated on the basis of the original study to be above 0.2 microT, and 21 higher than 0.4 microT, a threshold above which a raised risk has been observed. First, surveys were carried out outside the property boundaries of all 196 study homes, and then, where informed consent had been obtained, assessments were conducted inside the properties of 19 homes. The study found that low-voltage (LV) sources associated with the final electricity supply accounted together for 77% of exposures above 0.2 microT, and 57% of those above 0.4 microT. Most of these exposures were linked to net currents in circuits inside and/or around the home. High-voltage (HV) sources, including the HV overhead power lines that are the focus of public concern, accounted for 23% of the exposures above 0.2 microT, and 43% of those above 0.4 microT. Public health interest has focused on the consideration of precautionary measures that would reduce exposure to power frequency magnetic fields. Our study provides a basis for considering the options for exposure mitigation in the UK. For instance, in elevated-exposure homes where net currents are higher than usual, if it is possible to reduce the net currents, then the exposure could be reduced for a sizeable proportion of these homes. Further investigations would be necessary to determine whether this is feasible. PMID- 17341804 TI - Videoscopic assessment of the maintenance status of gamma radiography exposure containers employed in Brazil. AB - Industrial radiography is the most frequent method of non-destructive testing (NDT) used by Brazilian industrial facilities for investigating the material integrity of a test object. In Brazil, industrial radiography employs around 220 x-ray and 290 gamma radiography machines. About 90% of the latter uses iridium ((192)Ir) sources. The large majority of (192)Ir projectors in operation in Brazil have been in continuous usage for more than 25 years, which means that they are old and worn-out. Usually the majority of accidents concerning gamma radiography occur during the return of the source into the exposure container. Poor maintenance or imperfections of the internal channel of the exposure container can lead to accidental source exposure. In the present work the internal tube of 65 gamma machines from nine Brazilian companies that render gamma radiography services were analysed using an industrial videoscope. The internal images from the projectors were compared with the internal image of an apparatus that had never been used, i.e. has never received a radioactive source. From the 65 machines evaluated, nine showed irregularities of the internal tube. It was also observed that each company follows a different methodology for the maintenance and lubrication of the exposure containers and drive cables. PMID- 17341805 TI - Radionuclide content of local and imported cements used in Egypt. AB - The activity concentrations of natural and artificial gamma-ray emitting radionuclides in local and imported cement have been investigated during the period from 2000 to 2003 using a 50% HPGe gamma-spectroscopy system. The total numbers of local and imported samples were 29 and 8, respectively. The results showed a low activity concentration of (137)Cs in both the local and imported samples. The only exception was found in one imported Portland cement (2.8 +/- 0.2 Bq kg(-1)) and one local blast furnace slag cement (1.9 +/- 0.3 Bq kg(-1)). The average activity concentrations of (226)Ra, (232)Th and (40)K in local cement were 33 +/- 17, 14 +/- 2.4 and 45 +/- 26 Bq kg(-1), respectively, whereas those in imported cement were 27 +/- 7, 8 +/- 7 and 134 +/- 22 Bq kg(-1), respectively. The results showed that blast furnace slag cement contains the highest level of natural radioactivity, whereas white cement contains the lowest levels. The measured activity concentrations of the detected radionuclides were compared with other measurements carried out in Egypt and elsewhere. Radium-equivalent activities were also calculated to assess the radiation hazards arising from using such material in the construction of dwellings. Generally, the radium equivalents of the analysed samples were smaller than the guideline limit of 370 Bq kg(-1). PMID- 17341806 TI - A study of photon interaction parameters in some commonly used solvents. AB - Various parameters of dosimetric interest such as mass attenuation coefficients, effective atomic numbers and electron densities of some commonly used solvents such as acetonitrile (C(4)H(3)N), butanol (C(4)H(9)OH), chlorobenzene (C(6)H(5)Cl), diethylether (C(4)H(10)O), ethanol (C(2)H(5)OH), methanol (CH(3)OH), propanol (C(3)H(7)OH) and water (H(2)O) were computed in the wide energy range of 10 keV-100 GeV. A comparative study of two different methods used to compute effective atomic numbers has been done. It is observed that in the intermediate energy region (0.1-5 MeV), the mass attenuation coefficient values becomes almost the same for all the solvents, and the effective atomic number and electron density show almost constant values, whereas significant variation is observed in both lower (10-100 keV) and higher (5 MeV-100 GeV) energy regions for all the solvents, which may be due to the dominance of different partial interaction processes in different energy regions. PMID- 17341807 TI - ReCLAIM v2.0: a spreadsheet tool for calculating doses and soil/water radionuclide screening levels for assessment of radioactively contaminated land. AB - This note describes an electronic spreadsheet tool called ReCLAIM v2.0, developed by Nexia Solutions Ltd. The tool calculates doses to exposure groups for assessment of radioactively contaminated land including UK Nuclear Licensed sites on an individual exposure pathway basis and on a multiple exposure pathway basis constituting various specifiable scenarios. It also calculates soil/water screening levels of individual radionuclides with reference to selected exposure pathways and a dose target, and considers radionuclide additivity. Subject to agreement with a ReCLAIM disclaimer, the tool, with accompanying documentation (User Guide and Verification Report), can be downloaded without cost from the website (www.nexiasolutions.com/reclaim). PMID- 17341808 TI - Application of sunbeds for cosmetic purposes in Iran. AB - This note discusses the justification for using sunbeds for cosmetic purposes in Iran. The geographical location and ecology of the country, public knowledge about ultraviolet radiation and ultraviolet radiation protection and the Radiation Protection Act of Iran are considered during the discussion. It is concluded that the use of ultraviolet tanning appliances for cosmetic purposes in Iran cannot be justified. PMID- 17341811 TI - Characterization of the promoter of the mouse preproorexin gene. AB - The neuropeptide Orexin is involved in the regulation of the sleep-awake cycle and feeding behavior. We isolated a 22-kb genomic clone containing the 5' flanking region of the mouse Orexin promoter. We determined that the transcription start site (+1) is located 96 nucleotides upstream of the initiation codon. The start site region contained consensus sequences corresponding to the transcription initiator and TATA box. Analysis of promoter activity using PC12 cells showed that regions between -13 and +112 and between 1,868 and -780 contained nerve growth factor (NGF)-responsive positive regulatory element and a negative regulatory element respectively. PMID- 17341812 TI - Characterization of the NikA histidine kinase implicated in the phosphorelay signal transduction of Aspergillus nidulans, with special reference to fungicide responses. AB - We recently compiled a complete list of phosphorelay signal transduction components in the model filamentous fungus Aspergillus nidulans. In this study, we characterized a histidine protein kinase (designated NikA) that is found in many fungi, with special reference to responses to potent fungicides (iprodione and fludioxonil). We provided evidence that not only NikA, but also two downstream response regulators (SskA and SrrA) are crucially implicated in the mode of action of these fungicides, and also that the further downstream HogA MAPK cascade is exaggerated abnormally (or ectopically) in hyphae by the fungicides in a manner dependent on the NikA-SskA phosphorelay. PMID- 17341813 TI - Mutants of circadian-associated PRR genes display a novel and visible phenotype as to light responses during de-etiolation of Arabidopsis thaliana seedlings. AB - In Arabidopsis thaliana, it is currently accepted that certain mutants with lesions in clock-associated genes commonly display hallmarked phenotypes with regard to three characteristic biological events: (i) altered rhythmic expression of circadian-controlled genes, (ii) changes in flowering time, and (iii) altered sensitivity to red light in elongation of hypocotyls. During the course of examination of the clock-associated mutants of PSEUDO-RESPONSE REGULATORS, PRRs, including TOC1 (PRR1), we found that they commonly show another visible phenotype of anomalous greening responses upon the onset to light exposure of etiolated seedlings. These findings are indicative of a novel link between circadian rhythms and chloroplast development. PMID- 17341814 TI - Glucosylation of sucrose laurate with cyclodextrin glucanotransferase. AB - Sucrose monolauroyl esters were found to serve as substrates for cyclodextrin glucanotransferase (CGTase)-catalyzed transglucosidation reactions, affording new sucrose esters that have an additional 1-3 glucose residues on the pyranose ring of the sucrose moiety in the ester. PMID- 17341815 TI - Effects of dipeptides having a C-terminal lysine on the cholesterol 7alpha hydroxylase mRNA level in HepG2 cells. AB - Inducing expression of the cholesterol-catabolizing enzyme cholesterol 7alpha hydroxylase (CYP7A1) in the liver can be an effective strategy in preventing hypercholesterolemia and atherosclerosis. We used HepG2 cells to investigate the effects of 1 mM dipeptides having a C-terminal lysine group on the CYP7A1 mRNA level. We found that the dipeptides Asp-Lys, Glu-Lys, and Trp-Lys significantly increased the CYP7A1 mRNA level. PMID- 17341816 TI - Taurocholic acid does not induce apoptosis in HCT116 cells regardless of its intracellular concentration. AB - Hydrophobic bile acids but not hydrophilic bile acids induce apoptosis in HCT116 cells. We expressed sodium-dependent bile acid transporters in HCT116 cells, and the intracellular concentration of hydrophilic bile acids increased to that of the hydrophobic bile acids. But no sign of apoptosis was observed, which suggests a hydrophobic-bile acid-specific mechanism for the induction of apoptosis in HCT116 cells. PMID- 17341817 TI - High-level heterologous expression of Bacillus halodurans putative xylanase xyn11a (BH0899) in Kluyveromyces lactis. AB - The putative xyn11A structural gene (BH0899) encoding a family-11 xylanase from alkaliphilic Bacillus halodurans strain C-125 was heterologously expressed in the yeast Kluyveromyces lactis CBS 1065 and secreted to a level of 156 microg/ml under selective culture conditions in shake flasks. The Xyn11A production level in shake flask cultures of K. lactis CBS 1065 was higher than that reported for other xylanase genes placed under the control of the regulated LAC4 promoter on a plasmid containing an entire sequence of pKD1 from Kluyveromyces drosophilarium. Recombinant Xyn11A was highly active over pH range from 3 to 10, with maximal activity around pH 7. The enzyme showed a specific activity of 628 U/mg-protein on birchwood xylan as substrate, but no cellulase or beta-xylosidase activity. PMID- 17341818 TI - Genomics of Aspergillus oryzae. AB - The genome sequence of Aspergillus oryzae, a fungus used in the production of the traditional Japanese fermentation foods sake (rice wine), shoyu (soy sauce), and miso (soybean paste), has revealed prominent features in its gene composition as compared to those of Saccharomyces cerevisiae and Neurospora crassa. The A. oryzae genome is extremely enriched with genes involved in biomass degradation, primary and secondary metabolism, transcriptional regulation, and cell signaling. Even compared to the related species A. nidulans and A. fumigatus, an abundance of metabolic genes is apparent, with acquisition of more than 6 Mb of sequence in the A. oryzae lineage, interspersed throughout the A. oryzae genome. Besides the various already established merits of A. oryzae for industrial uses, the genome sequence and the abundance of metabolic genes should significantly accelerate the biotechnological use of A. oryzae in industry. PMID- 17341819 TI - Effects of rice proteins from two cultivars, Koshihikari and Shunyo, on cholesterol and triglyceride metabolism in growing and adult rats. AB - The effect and mechanism of two types of rice protein, one from regular japonica rice Koshihikari and another from rice cultivar Shunyo, with low glutelin and high prolamin content, on cholesterol and triglyceride metabolism were compared by feeding casein and soy protein to male Wistar strain rats 7 and 20 weeks old ad libitum for 2 weeks. The results in adult rats clearly indicated that both rice proteins had cholesterol-lowering effects in the plasma and the liver, comparable to soy protein, and the effects were accompanied with TG-lowering effects in the liver. Similar effects were also observed in growing rats when the diets were supplemented with cholesterol. The mechanism of the cholesterol lowering effects by these rice proteins cannot be explained solely by fecal steroid excretion, but the results indicate that not only regular rice protein but also Shunyo rice protein possesses improving effects on lipid metabolism, especially in the adult period. PMID- 17341820 TI - Highly induced DNA recombination mediated by membrane permeabilized recombinant cre protein in mouse primary cells. AB - To establish efficient induction of Cre mediated DNA recombination in primary cells, mouse embryonic fibroblast, keratinocyte, and primary preosteoblast, we tested various recombinant Cres by fusing of protein transduction domain in human immunodeficiency virus (HIV) transactivator of transcription (TAT-PTD) to the N- and/or C-terminus. HTC, modified Cre with PTD at the N-terminus, achieved the highest activity of DNA recombination for those primary cells. PMID- 17341821 TI - Enzymatic synthesis of dehydroderivatives from proline-containing cyclic dipeptides and their effects toward cell division. AB - We have previously isolated cyclo(L-Pro-L-Tyr) and cyclo(L-Phe-L-Pro) from an actinomycete by a novel enzymatic conversion-guided method. Their tetradehydro derivatives, cyclo(DeltaPro-DeltaTyr) and cyclo(DeltaPhe-DeltaPro), were enzymatically prepared. Neither of them inhibited cell division, in contrast to other tetradehydro cyclic dipeptides prepared previously. This result suggests that an NH proton in a diketopiperazine ring and/or conformation of the compound are important for the activity. PMID- 17341822 TI - Structural characterization of N-glycans of cauxin by MALDI-TOF mass spectrometry and nano LC-ESI-mass spectrometry. AB - Cauxin is a carboxylesterase-like glycoprotein excreted as a major component of cat urine. Cauxin contains four putative N-glycosylation sites. We characterized the structure of an N-linked oligosaccharide of cauxin using nano liquid chromatography (LC)-electrospray ionization (ESI) and matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (MALDI QIT-TOF MS) and MS/MS, and high-performance liquid chromatography (HPLC) with an octadecylsilica (ODS) column. The structure of the N-linked oligosaccharide of cauxin attached to (83)Asn was a bisecting complex type, Galbeta1-4GlcNAcbeta1 2Manalpha1-3(Galbeta1-4GlcNAcbeta1-2Manalpha1-6)(GlcNAcbeta1-4)Manbeta1 4GlcNAcbeta1-4(Fucalpha1-6)GlcNAc. PMID- 17341823 TI - Autoxidation of mono-, di-, and trilinoleoyl glycerols at different concentrations. AB - Mono-, di-, and trilinoleoyl glycerols were diluted with 1-undecanol or hexadecane to produce specific concentrations, and their oxidation processes were measured at 65 degrees C at 12% relative humidity. The rate constants for oxidation of the linoleoyl residue were proportional to the concentration for all substrates. This fact suggests that no intramolecular radical chain reaction between the linoleoyl residues occurred. PMID- 17341824 TI - Oral administration of a heat-killed cell preparation of Enterococcus faecalis strain EC-12 stimulates the gene expression of Na(+)-K(+)-2Cl- co-transporter 1 in rat ileal epithelial cells. AB - The effect of a heat-killed cell preparation of Enterococcus faecalis strain EC 12 (EC-12) on the gene expression of Na(+)-K(+)-2Cl(-) co-transporter 1 (NKCC1) in intestinal epithelial cells was evaluated by using rats. The NKCC1 gene in ileal epithelial cells was significantly up-regulated by the oral administration of EC-12. The results of this study suggest in vivo that EC-12 had the potential to stimulate intestinal NKCC1 expression. PMID- 17341825 TI - High-molecular-weight polyphenols from oolong tea and black tea: purification, some properties, and role in increasing mitochondrial membrane potential. AB - High-molecular-weight polyphenols from oolong and black teas increased mitochondrial membrane potential, as measured by a method using ciliated protozoan Tetrahymena and rhodamine 123. These polyphenols, referred to as mitochondrial activation factors (MAFs), were purified from oolong and black teas by solvent extraction and Toyopearl column chromatography. The number-average molecular weights of the MAFs were 9,000 to 18,000, and the weight-average molecular weights were 15,000 to 25,000. The MAFs increased the mitochondrial membrane potential more than catechins did. Treatment of the MAFs with tannase indicated that they contained galloyl residues. When the MAFs were hydrolyzed with HCl-n-BuOH, cyanidin and delphinidin were detected. The partial structure of the MAFs was analyzed by pyrolysis-gas chromatography-mass spectrometry, and nine compounds were identified. These results suggest that MAFs are heterogeneous polymers of flavan-3-ols and flavan-3-ol gallates with intermonomeric linkages of B-ring to B-ring and C-ring to A-ring. PMID- 17341826 TI - Reducing sludge production and the domination of Comamonadaceae by reducing the oxygen supply in the wastewater treatment procedure of a food-processing factory. AB - Sludge production was reduced remarkably by reducing the dissolved oxygen supply to less than 1 mg/l in the conventional wastewater treatment procedure of a food processing factory that produced 180 m(3) of wastewater of biochemical oxygen demand (BOD) of about 1,000 mg/l daily. DNA was extracted from the sludge and subjected to PCR amplification. The PCR product was cloned into a plasmid and sequenced. Estimation of the resident bacterial distribution by 16S rDNA sequences before and after improvement of the system suggested a remarkable gradual change in the major bacterial population from Anaerolinaeceae (15.6%) to Comamonadaceae (52.3%), members of denitrifying bacteria of Proteobacteria. Although we did not directly confirm the ability of denitrification of the resulting sludge, a change in the major final electron acceptors from oxygen to nitrate might explain the reduction in sludge production in a conventional activated sludge process when the oxygen supply was limitted. PMID- 17341827 TI - Physiological roles of calcineurin in Saccharomyces cerevisiae with special emphasis on its roles in G2/M cell-cycle regulation. AB - Calcineurin, a highly conserved Ca(2+)/CaM-dependent protein phosphatase, plays key regulatory roles in diverse biological processes from yeast to humans. Genetic and molecular analyses of the yeast model system have proved successful in dissecting complex regulatory pathways mediated by calcineurin. Saccharomyces cerevisiae calcineurin is not essential for growth under laboratory conditions, but becomes essential for survival under certain stress conditions, and is required for stress-induced expression of the genes for ion transporters and cell wall synthesis. Yeast calcineurin, in collaboration with a Mpk1 MAP kinase cascade, is also important in G(2) cell-cycle regulation due to its action in a checkpoint-like mechanism. Genetic and molecular analysis of the Ca(2+)-dependent cell-cycle regulation has revealed an elaborate mechanism for the calcineurin dependent regulation of the G(2)/M transition, in which calcineurin multilaterally activates Swe1, a negative regulator of the Cdc28/Clb complex, at the transcriptional, posttranslational, and degradation levels. PMID- 17341828 TI - Effects of CH-19 Sweet, a non-pungent cultivar of red pepper, on sympathetic nervous activity, body temperature, heart rate, and blood pressure in humans. AB - We investigated the changes in autonomic nervous activity, body temperature, blood pressure (BP), and heart rate (HR) after intake of the non-pungent pepper CH-19 Sweet and of hot red pepper in humans to elucidate the mechanisms of diet induced thermogenesis (DIT) due to CH-19 Sweet. We found that CH-19 Sweet activates the sympathetic nervous system (SNS) and enhances thermogenesis as effectively as hot red pepper, ant that the heat loss effect due to CH-19 Sweet is weaker than that due to hot red pepper. Furthermore, we found that intake of CH-19 Sweet does not affect systolic BP or HR, while hot red pepper transiently elevates them. These results indicate that DIT due to CH-19 Sweet can be induced via the activation of SNS as well as hot red pepper, but that the changes in BP, HR, and heat loss effect are different between these peppers. PMID- 17341829 TI - Ingestion of difructose anhydride III enhances absorption and retention of calcium in healthy men. AB - We examined the effects of a nondigestible disaccharide difructose anhydride III (DFAIII) on calcium absorption and retention by means of a human balance study of single-blind crossover design. Twelve healthy male subjects ingested 250 mg of shell powder as calcium carbonate (corresponding to 100 mg of calcium) with or without 1.0 g DFAIII three times a day for 13 d. In the last 4 d as a balance period, all urine and feces were collected and evaluated for calcium excretion. The apparent calcium absorption (mg/d) and rate of absorption (%) were higher, and those of retention were much higher, in the DFAIII group than in the control group. Furthermore, serum osteocalcin increased after the experimental period in the DFAIII group but not in the control group. These results indicate that DFAIII ingestion enhances intestinal calcium absorption, which might be beneficial for bone metabolism. PMID- 17341830 TI - Inhibition of increases in blood glucose and serum neutral fat by Momordica charantia saponin fraction. AB - Focusing on a functional component of Momordica charantia, saponin, we investigated its effects on serum glucose and neutral fat levels. Saponin was extracted as a butanol-soluble fraction (saponin fraction) from hot blast-dried Momordica charantia powder. The disaccharidase-inhibitory activity and the pancreatic lipase-inhibitory activity of the saponin fraction were measured, and in vivo sugar- and lipid-loading tests were performed. The saponin fraction inhibited disaccharidase activity and elevation of the blood glucose level after sucrose loading. The fraction also markedly inhibited pancreatic lipase activity and elevation of the serum neutral fat level after corn oil loading. Based on these findings, the main active component related to the anti-diabetic effect of Momordica charantia is present in the butanol fraction, and it may be saponin. The blood glucose and serum neutral fat-lowering effects of Momordica charantia were closely associated with its inhibitory activity against disaccharidase and pancreatic lipase. PMID- 17341831 TI - Some dinophycean red tide plankton species generate a superoxide scavenging substance. AB - Recent studies indicate that some raphidophycean red tide flagellates produce substances able to scavenge superoxide, whereas there have been no reports on superoxide scavenger production by dinophycean red tide flagellates. In this study, we examined the superoxide-scavenging activity of aqueous extracts from dinophycean red tide flagellates, Gymnodinium spp., Scrippsiella trochoidea, and Karenia sp., by a luminol analog L-012-dependent chemiluminescence (CL) method and an electron spin resonance (ESR)-spin trapping method, and compared the activity to that of raphidophycean red tide flagellates, Chattonella spp., Heterosigma akashiwo, and Fibrocapsa japonica. In the experiment applying the L 012-dependent CL method, only the aqueous extracts from raphidophycean red tide flagellates showed superoxide-scavenging activity. On the other hand, applying the ESR-spin trapping method, we found that the aqueous extracts from dinophycean red tide flagellates also showed superoxide-scavenging activity. This is the first report on the production of a superoxide-scavenger by dinophycean red tide flagellates. PMID- 17341832 TI - Production of mouse embryoid bodies with hepatic differentiation potential by stirred tank bioreactor. AB - Embryonic stem (ES) cells can differentiate into functional hepatic lineage cells, which can potentially be used in biomedicine. To obtain hepatic lineage cells from ES cells, embryoid bodies (EBs) must be formed. In this study, we developed an EB formation system using a spinner flask for mass production of EBs. ES cells were inoculated into the spinner flask, where they formed EBs within 4 d. The EBs were then transferred into an attached culture for hepatic differentiation. To verify the hepatic lineage cells, albumin secretion and hepatic-specific gene expression were examined. We found that EBs formed by either the spinner flask or hanging drops exhibited similar albumin secretion potential and hepatic-specific gene expression. We conclude that the spinner flask method can be used to produce mouse EBs that can be used to mass produce hepatic lineage cells for use in biomedicine. PMID- 17341833 TI - Structure and properties of the recombinant NADH-cytochrome b5 reductase of Physarum polycephalum. AB - A cDNA for NADH-cytochrome b(5) reductase of Physarum polycephalum was cloned from a cDNA library, and the nucleotide sequence of the cDNA was determined (accession no. AB259870). The DNA of 943 base pairs contains 5'- and 3'-noncoding sequences, including a polyadenylation sequence, and a coding sequence of 843 base pairs. The amino acid sequence (281 residues) deduced from the nucleotide sequence was 25 residues shorter than those of vertebrate enzymes. Nevertheless, the recombinant Physarum enzyme showed enzyme activity comparable to that of the human enzyme. The recombinant Physarum enzyme showed a pH optimum of around 6.0, and apparent K(m) values of 2 microM and 14 microM for NADH and cytochrome b(5) respectively. The purified recombinant enzyme showed a typical FAD-derived absorption peak of cytochrome b(5) reductase at around 460 nm, with a shoulder at 480 nm. These results suggest that the Physarum enzyme plays an important role in the organism. PMID- 17341834 TI - 2-O-alpha-D-glucopyranosyl-L-ascorbic acid scavenges 1,1-diphenyl-2 picrylhydrazyl radicals via a covalent adduct formation. AB - The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging mechanism of 2-O alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) was studied. We found two undefined products, named X and Y, in the reaction mixture of AA-2G and the DPPH radical under acidic conditions by HPLC analysis. The reaction mixture was further subjected to LC-MS analysis. X was found to be a covalent adduct of AA-2G and the DPPH radical. On the other hand, Y could not be identified, probably because it was a mixture. A time-course study of the radical-scavenging reaction revealed that one molecule of AA-2G scavenged one molecule of DPPH radical to generate an AA-2G radical, which readily reacted with another molecule of the DPPH radical to form a covalent adduct (X). Subsequently, this adduct slowly quenched a third molecule of the DPPH radical, resulting in reaction products (Y). Therefore, one molecule of AA-2G has only one oxidizable -OH group, but can scavenge three molecules of the DPPH radical. The radical-scavenging mechanism of AA-2G elucidated in this study should be useful in understanding the biological roles of AA-2G per se in the food and cosmetic fields. PMID- 17341835 TI - Properties and physiological functions of UDP-sugar pyrophosphorylase in Arabidopsis. AB - UDP-sugar pyrophosphorylase catalyzes the conversion of various monosaccharide 1 phosphates to the respective UDP-sugars in the salvage pathway. Using the genomic database, we cloned a putative gene for UDP-sugar pyrophosphorylase from Arabidopsis. Although relatively stronger expression was detected in the vascular tissue of leaves and the pollen, AtUSP is expressed in most cell types of Arabidopsis, indicating a housekeeping function in nucleotide sugar metabolism. Recombinant AtUSP expressed in Escherichia coli exhibited broad specificity toward monosaccharide 1-phosphates, resulting in the formation of various UDP sugars such as UDP-glucose, -galactose, -glucuronic acid, -xylose and -L arabinose. A loss-of-function mutation in the AtUSP gene caused by T-DNA insertion completely abolished male fertility. These results indicate that AtUSP functions as a UDP-sugar pyrophosphorylase in the salvage pathway, and that the generation of UDP-sugars from monosaccharide 1-phosphates catalyzed by AtUSP is essential for pollen development in Arabidopsis. PMID- 17341836 TI - Screening of drugs that suppress Ste11 MAPKKK activation in yeast identified a c Abl tyrosine kinase inhibitor. AB - The yeast MAPKKK Ste11 activates three MAP kinase pathways, including pheromone signaling, osmosensing, and pseudohyphal/invasive growth pathways. We identified two chemical compounds, BTB03006 and GK03225, that suppress growth defects induced by Ste11 activation in diploid yeast cells. BTB03006, but not GK03225, was found to suppress growth defects induced by both alpha-factor and Ste4 G(beta) overexpression in the pheromone signaling pathway, suggesting that GK03225 is an osmosensing pathway-specific inhibitor. We also performed genome wide suppressor analysis for Ste11 activation, using a yeast deletion strains collection, and identified PBS2 and HOG1, and several genes associated with chaperone functions, which represent potential target proteins of the drugs screened from Ste11 activation. GK03225 possesses an Iressa-like quinazoline ring structure, and its chemical analog, 11N-078, suppresses c-Abl human tyrosine kinase activity. These results suggest that drug screening in yeast can identify human tyrosine kinase inhibitors and other drugs for human diseases. PMID- 17341837 TI - Okara, soybean residue, prevents obesity in a diet-induced murine obesity model. AB - We examined the effect of okara on the prevention of obesity in mice. A modified AIN-76 diet with a high fat content (14.1% of crude fat) was used as a basal diet. Male ICR mice were fed ad libitum with the basal diet or a dried okara supplemented basal diet (10, 20, or 40%) for 10 weeks. The okara intake dose dependently suppressed the development of body weight and epididymal white adipose tissue (EWAT), and prevented an increase of plasma lipids, including total cholesterol, LDL cholesterol, and non-esterified fatty acid. The okara intake also prevented steatosis in the liver. Real-time RT-PCR revealed that the okara intake induced down-regulation of the fatty acid synthetase gene and up regulation of the cholesterol 7 alpha-hydroxylase (CYP7A1) gene in the liver. We also found that the okara intake caused a marked reduction in the expression of leptin and TNF-alpha genes in EWAT. Our results suggest that okara is beneficial in preventing obesity. PMID- 17341838 TI - Computer-aided design of the stability of pyruvate formate-lyase from Escherichia coli by site-directed mutagenesis. AB - Using computer-aided design of single-site mutations, three amino acid residues determined by changes in folding free energy between wild-type (wt) and mutant proteins were exchanged to enhance the stability of pyruvate formate-lyase (PFL). The mutant enzymes were tested for properties such as optimum temperature, optimum pH, kinetic parameters, and stability to temperature. There were two mutant variants, Glu336Cys and Glu400Ile, that exhibited increased thermostability as compared to the wt enzyme. The melting temperatures (T(m), the temperature at which 50% inactivation occurs after heat treatment for 20 min) of Glu336Cys and Glu400Ile increased by 3.7 and 2.2 respectively. They also showed an increase in half life of about 1.80 and 2.21-fold, whereas Ala273Cys showed a slight decrease as compared with the wt enzyme. PMID- 17341839 TI - Antibacterial activity of a virgatusin-related compound. AB - The relationship between antibacterial activity of tetra-substituted tetrahydrofuran lignans (1-4) and their absolute configurations was tested. Only compound 4 among two virgatusins and two related compounds exhibited growth inhibitory activity against the Gram-positive bacteria Bacillus subtilis, Staphylococcus aureus and Listeria denitrificans. Compound 4 affected the growth of B. subtilis in a bactericidic manner, and its ability to dissipate the cytoplasmic membrane potential was investigated using the fluorescence probe 3,3' dipropylthiadicarbocyanine iodide. These results suggested that compound 4 damages cells by causing the loss of the proton motive force and disruption of the cellular integrity of the membrane, leading to cell death. In addition, it was shown that the antibacterial activity of a lignan was closely related to its absolute configuration and functional groups. PMID- 17341840 TI - Synthesis of amino tetrahydrofuran lignan via an N,O-heterocyclic compound as an intermediate. AB - Tetrahydrofuran aminolignans bearing an amino group at the 8 position were synthesized via an N,O-heterocyclic compound that had been obtained by silylnitronate cycloaddition. PMID- 17341841 TI - Synergistic effects of adenosine A2A antagonist and L-DOPA on rotational behaviors in 6-hydroxydopamine-induced hemi-Parkinsonian mouse model. AB - In this study, we examined the combination effects of L-DOPA and adenosine receptor antagonists on rotational behaviors in a hemi-Parkinsonian mouse model induced by unilateral 6-hydroxydopamine (6-OHDA) injection. The adenosine A(2A) antagonist SCH-58261, but not the A(1)-receptor antagonist 8-cyclopentyl-1,3 dipropylxanthine or A(2B)-receptor antagonist alloxazine, synergistically potentiated the L-DOPA-induced rotational behaviors in the 6-OHDA-lesioned mice. In addtion, the 6-OHDA-induced lesions of the dopaminergic system did not affect the in vivo binding of an adenosine A(2A)-receptor tracer [(11)C]SCH-442416 in the striatatum. These findings suggest that adenosine A(2A) antagonists are extremely useful for pharmacotherapy of L-DOPA in Parkinson's disease patients. PMID- 17341842 TI - Pravastatin inhibits arrhythmias induced by coronary artery ischemia in anesthetized rats. AB - We have reported that chronically administered pravastatin prevented coronary artery reperfusion-induced lethal ventricular fibrillation (VF) in anesthetized rats without lowering the serum cholesterol level. The present study was undertaken to evaluate whether pravastatin prevents ischemia-induced lethal VF, simultaneously examining myeloperoxidase (MPO) activity in ischemic myocardial tissues. Anesthetized rats were subjected to 30-min ischemia and 60-min reperfusion after chronic administration of pravastatin (0.02, 0.2, and 2 mg/kg), fluvastatin (2 and 4 mg/kg), or vehicle for 22 days, orally, once daily. ECG and blood pressure were continually recorded, and MPO was measured by a spectrophotometer. Pravastatin and fluvastatin significantly (P<0.05) decreased MPO activities, but only pravastatin decreased the incidence of ischemia-induced lethal VF. Both statins had no significant effects on body weight, blood pressure, heart rate, and QT interval as we reported earlier. Our results prove further that pravastatin has benefits to decrease cardiovascular mortality beyond its cholesterol-lowering effect. Pravastatin is more potent than fluvastatin in prevention of arrhythmias. A decrease in the neutrophil infiltration may be partly involved in the inhibitory effect of pravastatin on the ischemia-induced VF. PMID- 17341843 TI - Clozapine prevents a decrease in neurogenesis in mice repeatedly treated with phencyclidine. AB - It has recently been suggested that neurogenesis in the dentate gyrus is decreased in schizophrenia and this phenomenon may contribute to the pathogenesis of the disorder. Since repeated administration of psychostimulants such as phencyclidine (PCP), MK-801, and methamphetamine (METH) induces schizophrenia like behavioral changes in animals, we investigated whether repeated administration of these psychostimulants affects neurogenesis in the dentate gyrus of mice. Newborn cells were labeled by bromodeoxyuridine (BrdU) and detected by immunohistochemistry. Repeated administration of PCP and MK-801, but not METH, resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus. PCP-induced decrease in the number of BrdU-labeled cells was negated by co-administration of clozapine, but not haloperidol, although repeated antipsychotics treatment by themselves had no effect. Furthermore, co administration of D-serine and glycine, but not L-serine, inhibited the PCP induced decrease in the number of BrdU-labeled cells. These results suggest that chronic dysfunction of NMDA receptors causes a decrease in neurogenesis in the dentate gyrus. PMID- 17341844 TI - Aspirin may exert its antipyresis by inhibiting the N-methyl-D-aspartate receptor dependent hydroxyl radical pathways in the hypothalamus. AB - Recent findings have suggested that the N-methyl-D-aspartate (NMDA) receptor dependent hydroxyl radical pathway in the hypothalamus of rabbit brain may mediate the fever induced by lipopolysaccharide (LPS). The aim of this study was to investigate whether aspirin exerts its antipyresis by suppressing hypothalamic glutamate and hydroxyl radicals in rabbits. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determination of both glutamate and hydroxyl radicals in situ. It was found that intravenous (i.v.) injection of LPS, in addition to inducing fever, caused increased levels of both glutamate and hydroxyl radicals in the hypothalamus. Pretreatment with aspirin (10 - 60 mg/kg, i.v.) one hour before an i.v. dose of LPS significantly reduced the febrile response and attenuated the LPS-induced increased levels of both glutamate and hydroxyl radicals in the hypothalamus. The increased levels of prostaglandin E(2) (PGE(2)) in the hypothalamus induced by LPS could be suppressed by aspirin pretreatment. The data indicate that systemic administration of aspirin, in addition to suppressing PGE(2) production, may exert its antipyresis by inhibiting the NMDA receptor-dependent hydroxyl radical pathways in the hypothalamus during LPS fever. PMID- 17341845 TI - Hemin modulates cytokine expressions in macrophage-derived foam cells via heme oxygenase-1 induction. AB - Lipid-laden foam cells were considered to be targets for therapeutic intervention in atherosclerosis. Several studies proposed new approaches to alter both lipid accumulation and inflammatory responses in macrophages. Finding anti-inflammatory signals during foam cell formation would provide new valid targets for anti atherosclerotic treatment. The aim of the present study was to see whether oxidized low-density lipoprotein (ox-LDL) can active heme oxygenase (HO)-1 expression level in a human monocyte line, U937 cells, associated with the increase of cytokine secretion. We used hemin (HO-1 activator) and zinc protoporphyrin IX (ZnPP IX, HO-1 inhibitor) to determine the effect of HO-1 on the regulation of cytokine expressions. The results showed that hemin can significantly decrease pro-inflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha levels, while enhancing IL-10 production in a dose-dependent manner in U937 foam cells. ZnPP IX did not significantly affect cytokine levels in foam cells. Our present results suggested that HO-1 is an important anti-inflammatory therapeutic target through inhibiting pro inflammatory cytokines and enhancing anti-inflammatory cytokines for the management of atherogenesis. PMID- 17341846 TI - Vesicular release of prolactin from preformed prolactin granules is stimulated by soluble factor(s) from the anterior pituitary of lactating rats. AB - This study demonstrates that conditioned media (CM) from the anterior pituitary gland (AP) of lactating rats contains soluble factors that promote in vitro prolactin (PRL) release from the pituitary glands of male rats. CM-induced PRL release was confirmed by polyacrylamide gel electrophoresis, ELISA and bioassay. In cultured AP cells challenged with CM, increased intracellular staining with the dye FM1-43 was observed, suggesting vesicular PRL release and subsequent endocytosis. The percentage and hormone content of PRL-containing cells but not of growth hormone-containing cells increased in cultured male AP cells when exposed to CM. When the release of PRL, prelabeled with [3H] leucine for 30 min to 24 h was examined, no stimulatory effect of CM was observed, suggesting that released PRL originates from hormone synthesized more than 24 h earlier. Accordingly, the PRL content of mature granules from male pituitary tissues decreased after CM treatment. These findings were confirmed by electron microscopy immunogold PRL labeling. Treatment with inhibitors of protein synthesis or vesicle trafficking between the endoplasmic reticulum and the Golgi complex did not prevent the stimulatory effect of CM on PRL release. However, blockage of traffic to the plasma membrane completely abolished the effect of CM. These results suggest that CM from the AP of lactators contains soluble factor(s) capable of inducing rapid vesicular release of PRL in the male AP, which originates from preformed, mature granules by mechanisms independent of protein synthesis. PMID- 17341847 TI - Rap1/B-Raf signaling is activated in neuroendocrine tumors of the digestive tract and Raf kinase inhibition constitutes a putative therapeutic target. AB - OBJECTIVE: Molecular pathogenesis of digestive neuroendocrine tumors (dNETs) is largely unknown. Recently, the serine-threonine kinase B-Raf was identified as an oncogene in endocrine cancer such as thyroid carcinoma. In endocrine cells, the small G-protein Rap1 stimulates mitogen-activated protein kinase (MAPK) signaling by activating B-Raf. We examined the expression of Rap1 and B-Raf in dNETs and their contribution to MAPK signaling in neuroendocrine cell lines. In addition, we explored the effect of suppressing B-Raf kinase by the recently developed inhibitor BAY43-9006 (Sorafinib) on growth, apoptosis and MAPK activation neuroendocrine cell lines. METHODS AND RESULTS: Expression of Rap1 and B-Raf in dNETs (19 insulinomas, 15 carcinoid tumors and 10 gastrinomas) was examined by immunohistochemistry, which revealed that Rap1 and B-Raf were highly prevalent in the majority of dNETs. Overexpression of Rap1 and B-Raf activated MAPK extracellular dependent kinase (ERK) ERK-2 and ERK-dependent transcription factor Elk-1 in neuroendocrine cell lines Bon and INS-1. Suppression of B-Raf by BAY43 9006 inhibited growth and induced apoptosis in Bon and INS-1 cells. In addition, BAY43-9006 suppressed phosphorylation of MAPK ERK1/2 and its upstream kinase MEK1/2 in Bon and INS-1 cells. CONCLUSION: These results indicate that Rap1-B-Raf signaling may contribute to pathogenesis of dNETs and provides a molecular target for treatment of dNETs. PMID- 17341848 TI - Impaired intestinal gas clearance during marked hyperglycemia in patients with functional abdominal bloating. AB - BACKGROUND: Especially in patients with functional intestinal disorders, impaired intestinal gas transit can be involved in abdominal symptom generation. We have previously demonstrated an acceleration of intestinal gas clearance in health during acute fasting hyperglycemia and hypothesize that in patients with functional abdominal bloating this mechanism may fail. METHODS: In 14 healthy subjects and 14 patients with functional abdominal bloating we compared effects of acute fasting hyperglycemia (approximately 12 mmol/l) and during euglycemia (control studies) on intestinal gas dynamics. Gas was infused into the jejunum (12 ml/min) for 120 min while rectal gas evacuation was continuously measured; perception and abdominal girth changes were separately evaluated. RESULTS: Marked hyperglycemia accelerated gas evacuation (-98 (53) ml 1 h intestinal gas retention) in health. In patients with functional abdominal bloating, marked hyperglycemia failed to accelerate gas transit and intestinal gas retention developed (421 (116) ml 1 h intestinal gas retention, p < 0.05 vs. health) which results in increased abdominal symptoms (perception score >3) and abdominal distension (>3 mm girth increment) as compared with control subjects (p < 0.05 for both). CONCLUSION: Intestinal gas clearance is delayed in patients with functional abdominal bloating and the increase in gas clearance during acute hyperglycemia in healthy volunteers does not occur in these patients. PMID- 17341849 TI - Graft versus host disease after orthotopic liver transplantation documented by analysis of short tandem repeat polymorphisms. AB - We report a case of graft versus host disease after liver transplantation in which the diagnosis was made by short tandem repeat analysis. A retrospective analysis using a bone marrow sample showed the presence of chimerism already at a time when the characteristic full clinical picture of graft versus host disease had not yet developed, opening the way for the early diagnosis and treatment. PMID- 17341850 TI - Two common reasons of malabsorption syndromes: celiac disease and Whipple's disease. AB - Malabsorption syndromes are commonly caused by pathological interferences of normal digestive processes. In the last several years major advances in the diagnosis and treatment of these syndromes has emerged. This review will focus on diseases in which the mucosal phase of the digestive process is predominately disturbed, including celiac disease and Whipple's disease. Since most diagnostic tests have a limited availability, it will also provide a diagnostic algorithm of malabsorption syndromes. PMID- 17341851 TI - COX-2 inhibition and the prevention of gastric cancer. PMID- 17341853 TI - Newly developed biodegradable stents for benign gastrointestinal tract stenoses: a preliminary clinical trial. AB - We developed an Ultraflex-type stent by knitting polylactic acid monofilaments. The purpose of this study was to evaluate the stent's clinical usefulness for treating benign stenoses in the gastrointestinal tract. The radial force of the biodegradable stent was compared with those of commercially available metallic stents. The measured radial force of the new biodegradable stent was higher than that of commercially available metallic stents. The biodegradable stents were applied in 2 patients with benign gastrointestinal stenoses. The first patient was a 19-year-old female with esophageal stenosis, due to drinking of caustic potash in an attempt to commit suicide. The second patient was a 75-year-old male who had a stenosis at the anastomotic site after esophageal cancer resection. In both cases, the placement of the stent was performed successfully, and the patients' complaints improved immediately after stent placement. There were no complications during stent placement. The stenosis had not recurred at the six month follow-up examination. In conclusion, the newly developed biodegradable stents were useful in treating benign stenoses of the alimentary tract. PMID- 17341852 TI - Celecoxib inhibits Cdx2 expression and prevents gastric cancer in Helicobacter pylori-infected Mongolian gerbils. AB - BACKGROUND/AIM: The aim of this study was to see whether administration of celecoxib, a selective COX-2 inhibitor, prior to the appearance of intestinal metaplasia could prevent the development of gastric cancer in Helicobacter pylori infected Mongolian gerbils. METHODS: Fifty-two Mongolian gerbils were divided into 3 groups and given 5 biweekly doses of N-methyl-N-nitrosourea (MNU; 30 ppm). At week 12, group 2 (n = 20) and group 3 (n = 22) gerbils were then given an injection of H. pylori, while group 1 controls (n = 10) received Brucella broth alone. In addition, 7 weeks after H. pylori inoculation, at week 19, group 3 gerbils also received a 36-week administration course of celecoxib (1,500 ppm) in their diet. The incidence of gastric adenocarcinoma was determined at week 54 by histological analysis. COX-2 and Cdx2 protein expression and COX activity were evaluated for each group. The extent of intestinal metaplasia, Cdx2 and MUC2 expression, and the apoptotic index were evaluated semi-quantitatively by immunohistochemistry. RESULTS: The incidence of gastric adenocarcinoma was: group 1, 0% (0/10); group 2, 65% (13/20), and group 3, 23% (5/22; p < 0.05). Continuous celecoxib administration significantly reduced COX activity and COX-2 protein expression, Cdx2 and MUC2 protein immunoreactivity, and the extent of Alcian blue periodic acid-Schiff-positive intestinal metaplasia in H. pylori-infected gerbils. Celecoxib also induced apoptosis in these gerbils. Significant inhibition of Cdx2 expression in group 3 gerbils was also shown by Western blot analysis. CONCLUSIONS: Prior to the first appearance of intestinal metaplasia, timely administration of celecoxib prevents gastric cancer occurrence by disrupting the progression of intestinal metaplasia into gastric carcinoma through its inhibition of Cdx2 expression in MNU-pretreated H. pylori-infected Mongolian gerbils. PMID- 17341854 TI - Reversal of protein-losing enteropathy with heparin therapy in an adult patient with congenital heart disease. PMID- 17341855 TI - SEN and hepatitis virus infections in nontransfused children and pediatric thalassemia patients with multiple transfusions in Taiwan. AB - BACKGROUND: Southern Taiwan is a hepatitis B and C viruses (HBV, HCV) endemic area. SEN virus (SENV) infection has been suggested as transfusion-related hepatitis. Two variants of SENV (SENV-D and SENV-H) have been studied in non transfused children and transfusion-dependent thalassemia patients. METHODS: Sera of 67 non-transfused children and 55 pediatric thalassemia patients with multiple transfusions were tested for SENV-D and SENV-H DNAs, liver function, iron status, HBV and HCV markers. RESULTS: The prevalence of SENV (D or H), SENV-D, SENV-H infection, and SENV-D/H coinfection was significantly lower in nontransfused children than in thalassemia patients (22.4, 20.9, 5.0 and 1.5%, respectively, versus 67.3, 52.7, 40.0 and 25.5%, respectively, p < 0.001). The serum alanine aminotransferase (ALT) levels in thalassemia patients with SENV infection alone were significantly lower than levels in patients with SENV/HCV co-infection (p < 0.05), but not different when compared with those without SENV/HCV infection. SENV viremia was not associated with elevated ALT levels in thalassemia patients. SENV viremia did not increase the risk of HCV infection in thalassemia patients. CONCLUSIONS: SENV infection is high among non-transfused controls in Taiwan. Transfusion significantly increases the relevance of SENV infection. SENV viremia was not associated with the ALT levels in thalassemia patients. PMID- 17341856 TI - 'Soft medicine' is not always soft: the original sin of German drug legislation. PMID- 17341858 TI - PsoReg--the Swedish registry for systemic psoriasis treatment. The registry's design and objectives. AB - With the introduction of new systemic drugs for the management of psoriasis, we felt an obligation in Sweden to establish a trusted tool to monitor their use. We formed PsoReg to create a solid, long-term database in order to analyze safety and effectiveness of different systemic psoriasis treatment regimens. PsoReg will provide information to help clinicians individualize therapy on a rational basis through evaluation of effectiveness and adverse effects in specific patient subgroups. Designed and managed by specialized health care professionals, PsoReg will enroll all psoriasis patients on systemic treatment to allow a fair comparison of old versus new-generation psoriasis treatments. PsoReg will even create benchmark data for quality assurance of the medical service. A web-based design allows real-time pharmacovigilance and enables the registry to assist clinicians in their day-to-day management of psoriasis patients. In this way PsoReg can become an integrated part of tomorrow's dermatology. PMID- 17341857 TI - Clinical questions asked by medical students: a learning tool for dermatology rotations. AB - BACKGROUND/AIMS: To determine whether having medical students answer self generated patient-specific questions in a clinical setting promotes learning. METHODS: Medical students rotating through dermatology clinics at the Denver Veterans' Affairs (VA) Medical Center were asked to formulate and answer one clinical question arising during patient encounters, and to complete a survey regarding their findings and experience. RESULTS: 49% (44/89) of rotating medical students completed the exercise. Self-generated questions frequently addressed therapy (61%, 27/44), prognosis (13%, 6/44), etiology/risk factors (7%, 3/44), and harm (5%, 2/44). The most frequently used sources of clinical information were journal abstracts/articles (55%, 24/44), UpToDate (50%, 22/44), websites (27%, 12/44) and printed textbooks (25%, 11/44). Medical students rated the impact of answers they obtained on a Likert scale of 1 (strongly disagree) to 5 (strongly agree) for the following: can be used to assist in patient's care (mean 4.1), improved care (mean 3.7), improved communication (mean 4.4), improved confidence in care (mean 4.2), improved knowledge (mean 4.6), and will improve future care (mean 4.5). CONCLUSIONS: Medical students report increased knowledge, confidence and patient care skills after completing a self-directed formal exercise consisting of formulating and answering a patient-specific clinical question. PMID- 17341859 TI - Three retinoid X receptor gene polymorphisms in plaque psoriasis and psoriasis guttata. AB - AIM: Polymorphisms in retinoid X receptors (RXRs) are very interesting from the point of view of a possible association of their variability with psoriasis. METHODS: A total of 293 patients with plaque psoriasis, 82 patients with psoriasis guttata and 202 control subjects were enrolled in this study focused on 3 polymorphisms in RXRA and RXRB gene associations. RESULTS: A marginally significant increase in AA allelic frequency of the RXRA A39526AA polymorphism in plaque psoriatic men compared to healthy men was proved. In women with psoriasis guttata, the higher risk for genotypes AA and TT in the RXRB 3'+140A/T polymorphism compared to healthy women was identified (p(corr) = 0.01). The genotypes A/A and AA/AA are more frequent in plaque psoriasis patients with a positive family history of psoriasis compared to the patients with a negative family history of psoriasis (p(corr) = 0.02). The A/A genotype is more frequent in patients with plaque psoriasis and repeated tonsillitis/tonsillectomy (p = 0.02). In the RXRB polymorphism, no genotype TT is observed in patients with psoriasis guttata with a positive personal history of repeated tonsillitis (p(corr) = 0.001). CONCLUSION: Individual gene characteristics of patients with psoriasis improve the possibilities of pharmacotherapy using pharmacogenomic approaches which could be further stratified in future according to the subtypes of psoriasis. PMID- 17341860 TI - Obesity and low-grade inflammation among young Finnish men with early-onset alopecia. AB - BACKGROUND: Previous investigations have revealed an association of androgenetic alopecia (AGA), especially in younger subjects with severe early-onset AGA, with ischemic heart disease. OBJECTIVE: To examine the possible association between early-onset alopecia and low-grade inflammation measured by high-sensitivity C reactive protein (hs-CRP) that has been recommended for the assessment of the cardiovascular disease (CVD) risk. METHODS: The study population consisted of young men (n = 727, aged 25-34 years) participating in a national survey. The grade of alopecia was assessed by a trained nurse using the Norwood/Hamilton Classification Scale. RESULTS: Men with moderate to extensive alopecia (17%) had a higher body mass index and larger waist, upper arm, hip and waist circumference than those with little to no alopecia (p < 0.05), and statistically insignificant differences were seen in the waist-to-hip circumference ratio (WHR), diastolic blood pressure and hs-CRP. With increasing hs-CRP, the mean WHR increased, but only among men with moderate to extensive alopecia (p = 0.043). CONCLUSION: Our findings show a relation between moderate to extensive alopecia and low-grade inflammation--a predictor of a future CVD--especially combined with central obesity, among men younger than 35 years. PMID- 17341861 TI - Inverse Klippel-Trenaunay syndrome: review of cases showing deficient growth. AB - BACKGROUND: Klippel-Trenaunay syndrome is defined by a coexistence of nevus flammeus and overgrowth of one or more limbs. Remarkably, however, deficient growth of an affected limb may likewise be noted. OBSERVATIONS: We collected from the literature a number of cases of Klippel-Trenaunay syndrome associated with deficient growth such as shortening or hypoplastic muscle mass of the affected extremity. DISCUSSION: The cause of the unusual deficient growth is unknown. Some patients may be compound heterozygotes carrying a 'plus' and a 'minus' allele at the responsible gene locus, and postzygotic recombination would give rise to two different cell clones homozygous for either allele. CONCLUSION: In order to give a name to such paradoxical cases, we propose the term 'inverse Klippel-Trenaunay syndrome'. PMID- 17341862 TI - Dermopathy and retinopathy in diabetes: is there an association? AB - BACKGROUND/AIMS: Diabetic dermopathy is the most common cutaneous marker of diabetes mellitus presenting as single or multiple well-demarcated brown atrophic macules, predominantly on the shins. Although diabetic dermopathy and diabetic retinopathy are both considered by some authors as manifestations of diabetic microangiopathy, only a few studies are published about their possible association. Our purpose was to investigate the association of diabetic dermopathy and diabetic retinopathy. METHODS: We conducted a cross-sectional study in an outpatient diabetes clinic during a 6-month period. One-hundred and eighty-one consecutive patients (8 cases of insulin-dependent diabetes mellitus and 173 cases of non-insulin-dependent diabetes mellitus) were examined for the presence of diabetic dermopathy and diabetic retinopathy. RESULTS: Forty-seven (26%) showed diabetic dermopathy and 68 patients (37.6%) suffered from diabetic retinopathy. The frequency of retinopathy in patients with diabetic dermopathy (44%; 30 cases) was significantly greater than in patients without dermopathy (15%; 17 cases; p < 0.0001). Retinopathy showed a statistically significant association with dermopathy [odds ratio (OR): 3.60; 95% confidence interval (CI): 1.53-8.44; p = 0.003] and diabetes duration (OR: 3.36; 95% CI: 1.67-6.77; p = 0.001). CONCLUSION: Our study further supports that diabetic dermopathy might be used as a telltale sign of diabetic retinopathy, necessitating more intensive ophthalmologic care, especially in long-lasting diabetes. PMID- 17341863 TI - Colour clusters for computer diagnosis of melanocytic lesions. AB - BACKGROUND: To overcome subjectivity and variability in the interpretation of dermoscopic images, image analysis programs, enabling the numerical description of melanocytic lesion images, have been developed. OBJECTIVES: Our aim was to assess a method for the description of colours in melanocytic lesion images, based on the subdivision of image colours into red, green and blue clusters. METHODS: Melanomas and naevi of the test set were described by means of 23 colour clusters previously selected by a training set comprising 369 melanocytic lesion images. The diagnostic performance obtained by this automated method was compared to sensitivity and specificity of diagnosis of 4 dermatologists. RESULTS: Colour cluster values significantly differed between melanomas and naevi. Moreover, sensitivity and specificity values of computer diagnosis were similar to those achieved by the dermatologists. CONCLUSION: Our image analysis program based on the assessment of one single parameter has the diagnostic accuracy of dermatologists employing dermoscopy on a regular basis. PMID- 17341864 TI - Impairment of sexual life in patients with psoriasis. AB - BACKGROUND: Sexual life can be severely affected in patients with psoriasis. However, this component is not often assessed by clinicians. OBJECTIVE: To estimate the prevalence of sexual impairment and its degree of association with clinical and personal factors among psoriasis patients. METHODS: Sexual life impairment was investigated in all eligible adults hospitalized with psoriasis in a dermatological hospital from February 2000 to February 2002, using answers to specific items from two dermatology-specific questionnaires, and from two psoriasis-specific questionnaires. Clinical severity and psychological problems were also evaluated. The same questionnaires were collected a month after hospital discharge, to estimate changes from baseline. RESULTS: Of 936 patients,from 35.5% (Psoriasis Disability Index) to 71.3% (Impact of Psoriasis on Quality of Life Questionnaire) reported to have experienced sexual problems because of psoriasis. A more severe disease and the presence of psychological problems were also associated with sexual impairment. At 1-month follow-up, a reduction of >75% in clinical severity was associated with a twofold probability of substantial improvement of sexual life. CONCLUSIONS: Sexual impairment is very frequent in patients with psoriasis. Single questions on sexual life from quality of life questionnaires provide a simple tool that may be useful in clinical practice to assess sensitive issues, and thus to provide better patient-physician communication. PMID- 17341865 TI - Preliminary experiences with Bio-Alcamid in HIV facial lipoatrophy. AB - BACKGROUND: Highly active antiretroviral therapy for HIV-infected patients causes metabolic changes known as the lipodystrophy syndrome. Autologous fat injections, dermal fat grafts, malar implants and injected fillers have been reported as treatment options. OBJECTIVE: To evaluate the results of HIV-infected patients treated with Bio-Alcamid for facial lipoatrophy. METHODS AND MATERIALS: Over a 3 year period, 13 HIV-infected patients with facial lipoatrophy had Bio-Alcamid injections for aesthetic purposes. The procedure was done under local anesthesia, and the amount of the injected material varied from 5 to 13 ml. Results were independently evaluated by patients and physicians. RESULTS: Most of the patients felt they had good to excellent results. Touch-ups were necessary for 2 patients; the added volume was 2-3 ml for each. No major complications were recorded. A small hematoma was noted in 1 patient. Overcorrection was attained in 2 cases, and some of the filler was removed at the patient's request. CONCLUSION: One of the greatest advantages of this filler is that, although permanent, it can be removed easily. We consider Bio-Alcamid to be a safe and useful correcting tool for patients suffering from drug-induced facial lipoatrophy. PMID- 17341867 TI - A pilot study on seborrheic dermatitis using pramiconazole as a potent oral anti Malassezia agent. AB - BACKGROUND: Seborrheic dermatitis is considered to be a Malassezia-driven disease. Little objective information is available so far from biometrological quantitative assessments of this skin condition. Pramiconazole is a novel triazole with potent in vitro antifungal activity, especially against Malassezia spp. OBJECTIVE: To study the sequential effects of pramiconazole on Malassezia, inflammation and epidermal changes. METHOD: This study was performed in 2 groups of subjects suffering from seborrheic dermatitis. The first group (n = 17) remained untreated and was used as control. Clinical, mycological and biometrological assessments were performed at inclusion and during the following 2 weeks. The second group of subjects (n = 10) received a single 200-mg oral dose of pramiconazole at inclusion. Clinical, mycological and biometrological evaluations were performed before and during 1 month following the single antifungal intake. For both parts of the study, several parameters were assessed including yeast density, desquamation, erythema, itching and sebum excretion. RESULTS: In the control group, no significant changes were observed in any of the parameters during the observation period. The findings were markedly different in the pramiconazole-treated subjects. The yeast density was significantly improved on days 3, 7 and 28. Desquamation, erythema, itching, and the global clinical evaluation as assessed by the patients and investigators became significantly improved on days 7 and 28. A trend in decrease of scaliness was noted. No effect on sebum excretion was evidenced. In conclusion, a single 200-mg dose of pramiconazole exhibitsin vivo efficacy in controlling some important clinical aspects of seborrheic dermatitis. Following a reduction in the number of yeasts on day 3, a decrease in the severity of clinical signs and symptoms occurred from day 7 onwards. Sebum excretion appeared uninvolved in the clearing process of seborrheic dermatitis. CONCLUSION: A single 200-mg dose of pramiconazole appears to abate seborrheic dermatitis. The density in Malassezia present on lesional skin is first decreased, followed by clearing of the clinical signs. PMID- 17341866 TI - The efficacy and safety of topically applied indigo naturalis ointment in patients with plaque-type psoriasis. AB - BACKGROUND: It has been reported in the Chinese literature that indigo naturalis exhibits potential antipsoriatic effects in systemic therapy. OBJECTIVE: To evaluate the efficacy and safety of topically applied indigo naturalis on treating plaque-type psoriasis and to analyze the histological change in skin tissues. METHODS: Fourteen patients with chronic plaque psoriasis were enrolled. The patients were topically applied with either indigo naturalis ointment or vehicle ointment on contralateral skin lesions daily for 8 weeks. Efficacy was evaluated on the basis of the clinical scores, including induration, scaling, erythema and clearing percentage. At the end of treatment, skin punch biopsies were taken and prepared for the immunohistochemical analysis. RESULTS: A significant reduction in clinical scores was achieved with topically applied indigo naturalis ointment. Analysis of biopsies showed a marked improvement of skin histology. The expressions of proliferating marker Ki-67 and inflammatory marker CD3 were decreased, but the differentiation marker such as filaggrin was increased in the epidermis after indigo naturalis ointment treatment. CONCLUSIONS: The results suggest that topical application of indigo naturalis ointment may be a novel, safe and effective therapy for psoriasis that is mediated, at least in part, by modulating the proliferation and differentiation of keratinocytes in epidermis, as well as by inhibiting the infiltration of T lymphocytes and therefore the subsequent inflammatory reactions in psoriatic lesions. PMID- 17341868 TI - Multicentric Castleman disease with cutaneous manifestations: report of 2 cases and comparison with systemic plasmacytosis. AB - We report 2 patients with multicentric Castleman disease. Both presented with multiple, indurated, hyperpigmented plaques, generalized lymphadenopathy and polyclonal hypergammaglobulinemia. Biopsy specimens showed infiltration of mature plasma cells and lymphocytes in the dermis and lymph nodes. Skin specimens were negative for human herpesvirus 8, latent nuclear antigen 1 and Epstein-Barr virus by in situ hybridization. PCR disclosed clonal T-cell receptor gene rearrangement in the bone marrow cells of 1 patient. We discuss the possible relationship between multicentric Castleman disease and systemic plasmacytosis as well as plasma cell proliferation. PMID- 17341869 TI - Dermoscopy of a plantar combined blue nevus: a simulator of melanoma. AB - Dermoscopy allows early detection of melanoma also on acral volar skin. The majority of melanocytic nevi on palms and soles may show three major dermoscopic patterns: the parallel-furrow pattern, the lattice-like pattern, and the fibrillar pattern. Melanomas at these sites are characterized by the parallel ridge pattern. We present the case of a 59-year-old woman who had an oval papule of bluish color, measuring 0.6 x 0.9 cm, localized on her left sole, that had been present, unchanged, for more than 10 years. Dermoscopy showed a parallel ridge pattern. The histopathological examination revealed a combined blue nevus. We present this case to underline that on acral volar skin also intradermal nevi, such as combined blue nevi, may dermoscopically exhibit a parallel ridge pattern, simulating melanoma. PMID- 17341870 TI - Poikiloderma of Civatte: a histopathological and ultrastructural study. AB - BACKGROUND: Poikiloderma of the face and neck (Civatte) has not been studied in depth for decades, especially as far as the histopathology is concerned. MATERIAL AND METHODS: We studied 50 consecutive patients with poikiloderma of Civatte (PC). Their evaluation included: history, physical examination, lesional skin biopsy and histological examination of sections stained with hematoxylin-eosin, PAS, Fontana-Masson, acid orcein Giemsa for elastic fibers and toluidine blue for mast cells. In 10 randomly selected subjects, a second skin biopsy was performed and specimens were examined under the electron microscope. RESULTS: There were 34 females (68%) and 16 males. The mean age at diagnosis was 47.8 years for females and 61.7 years for males. Histological examination revealed an atrophic (62%), flattened (84%) epidermis with hyperkeratosis (92%) and occasional follicular plugging (34%). In some cases, mild hydropic degeneration of the basal cell layer was evident (46%). Melanin was irregularly distributed in the lower epidermis (94%), and melanophages were often present in the dermis (92%). The most prominent and constant feature (100%) was solar elastosis of the papillary dermis. The blood vessels were almost invariably dilated (96%) with a mild perivascular lymphohistiocytic infiltrate (78%), sometimes with plasmacytes (56%). At the ultrastructural level, the epidermis showed only minor changes. The dermoepidermal junction was intact. The most constant findings were swelling and disruption of the collagen fibers as well as focal degeneration of the collagen bundles. Occasionally, several vacuolar spaces were found just under the basal lamina. Melanin-laden macrophages scattered in the dermis were also detected. CONCLUSIONS: PC shows distinct histological and ultrastructural features, supporting the theory that it represents a separate entity. The histology of PC is characteristic but not pathognomonic. On this basis, the differential diagnosis from Riehl's melanosis, poikiloderma atrophicans et vasculare and other acquired poikilodermas can be made. Ultrastructural findings were consistent with the histological findings. Changes of the dermal connective tissue (solar elastosis) predominated, providing morphological evidence for the role of ultraviolet radiation in the pathogenesis of PC. PMID- 17341871 TI - Bullous pemphigoid in a patient with Netherton's syndrome. PMID- 17341872 TI - Utility of FDG-PET for staging in a case of mycosis fungoides. PMID- 17341873 TI - Glans penis ulceration revealing Wegener's granulomatosis. PMID- 17341874 TI - Skin lesions as another possible clinical manifestation of mitochondrial toxicity in an HIV-infected patient. PMID- 17341875 TI - Bullous erysipelas caused by community-acquired methicillin-resistant Staphylococcus aureus. PMID- 17341877 TI - Cardiovascular collapse developing after topical anesthesia. PMID- 17341878 TI - Effect of external scrotal cooling on the viability of the testis with torsion in rats. AB - BACKGROUND AND AIM: Testicular damage due to ischemia during torsion is aggravated after reduction and reperfusion. The severity of the damage depends on the degree and duration of the torsion. Hypothermia has been successfully used in preserving the viability of ischemic organs for a prolonged period. Our aim is to evaluate the effect of external scrotal cooling in preserving testicular viability after spermatic cord torsion in rats. METHODS: 100 adult male Sprague Dawley rats were equally divided into ten groups. Exposure of the right testicle for either 4 or 8 h in groups 1 and 2 were the control groups. The rats in eight groups (3-10) underwent clockwise torsion of 1,080 degrees of the right testis around its longitudinal axis, for either 4 or 8 h. External scrotal cooling was applied during the torsion period in four groups. Half of the rats were sacrificed at the end of the torsion period, while the other rats underwent detorsion and were sacrificed 2 weeks later. All testicles were excised for histology. RESULTS: The histological results showed that external scrotal cooling decreased both immediate and late damage to the testis, caused by torsion. A moderate degree of injury was found in the contralateral testicle in rats after torsion of the right testicle for 8 h with application of external cooling and detorsion. CONCLUSION: External scrotal cooling is effective in preserving the viability of the torsed testis in rats. The injury of ischemia-reperfusion, although reduced by external cooling, may endanger the contralateral testis as well, if the duration of torsion is longer than 4 h. With increased duration of torsion, orchiectomy should be considered. Application of this treatment may reduce the injury in humans awaiting surgery. PMID- 17341879 TI - Allogeneic platelet gel with autologous cancellous bone graft for the treatment of a large bone defect. AB - BACKGROUND/AIMS: A 50-year-old type 2 diabetic male with a comminuted fracture of the tibia and delayed union after insufficient initial osteosynthesis with a resulting pseudoarthrosis was treated operatively by using a graft composed of platelet gel mixed with autologous cancellous bone. The essential idea of this therapy was to combine the healing capacities of platelet-derived growth factors and osteogenic stem cells and the modeling capacity of the gel. Due to a history of diabetes, allogeneic instead of autologous platelets were used. METHODS: The allogeneic platelet concentrate was ABO- and RhD-matched, leukocyte-depleted, irradiated and activated by human thrombin. The defect of 45 ml was filled with the graft mixture and fixed with an external fixator. RESULTS: Postoperative care was uneventful. After 6 months the graft was incorporated, the bone defect was fully bridged and full weight-bearing capacity was achieved. No side effects were observed and no platelet or HLA class I antibodies were detected. CONCLUSION: This case report shows that the clinical use of allogeneic platelet-derived growth factors is feasible and that a prospective study is necessary to prove the effectiveness and reproducibility of this therapeutic approach. PMID- 17341880 TI - [At the beginning of a new era--integration and differentiation]. PMID- 17341881 TI - [Science communication or how patient-oriented is research in complementary medicine?]. PMID- 17341882 TI - Mistletoe extract reduces the surgical suppression of natural killer cell activity in cancer patients. a randomized phase III trial. AB - BACKGROUND: Major surgery suppresses natural killer (NK) cell cytotoxic activity which is potentially harmful for cancer patients by favouring haematogenic tumour cell dissemination. The influence of a perioperative infusion of a standardized mistletoe extract (Iscador) on immune functions was tested in a prospective, sequential, randomized clinical trial. PATIENTS AND METHODS: Colorectal cancer patients undergoing open tumour resection were randomly assigned to either mistletoe infusion or no additional therapy. We hypothesized that mistletoe infusion improves NK cell activity and increases expression of MHC class II antigen HLA-DR on monocytes 24 h and 7 days after surgery, respectively. For statistical analysis we used a sequential study design. The decision boundaries for the two triangular tests were calculated for altogether 62 patients. RESULTS: The sequential study design allowed stopping the recruitment prematurely. NK cell activity differed significantly between the therapy groups 24 h after surgery (p = 0.027). The absolute number of HLA-DR molecules on monocytes did not differ 7 days after surgery. NK cell activity of patients treated with mistletoe extract did not change significantly during the course of the study (-7.9% 24 h after surgery), whereas HLA-DR expression changed significantly (-38.5% at day 7 after surgery). For control patients both parameters decreased significantly after surgery (NK cell activity: -44.4% at 24 h; HLA-DR expression: -32.9% at day 7 after surgery). CONCLUSION: Perioperative infusion of mistletoe extracts can prevent a suppression of NK cell activity in cancer patients. The impact of this therapy on relapse and survival should be tested in further studies. PMID- 17341883 TI - Prognos in the diagnosis of amalgam hypersensitivity a diagnostic case-control study. AB - OBJECTIVE: We aimed to investigate whether the Prognos device might be a useful tool in the diagnosis of disorders suspected to be due to dental amalgam fillings. PARTICIPANTS AND METHODS: A diagnostic case-control study was performed in 27 patients who complained about health problems attributed to amalgam (cases), 27 healthy volunteers with amalgam fillings (controls I), and 27 healthy amalgamfree volunteers (controls II). All participants were tested before and after application of 300 mg DMPS (2.3-dimercapto- 1-propanesulfonic acid) with Prognos, a diagnostic device for the energetic measurement of Traditional Chinese Medicine meridians. In addition, mercury was measured in blood, urine, and saliva, and a lymphocyte transformation test (LTT) was performed. RESULTS: Diagnoses derived from the first and second Prognos testing did not agree above chance (Cohen's Kappa = -0.11, 95% confidence interval -0.33 to 0.10; p = 0.30). Agreement for secondary outcome measures was poor, too. Prognos measurements did not differ between cases and controls. Correlations with measurements in urine, blood and saliva were low. CONCLUSION: In this study Prognos could not be shown to be a useful tool in the diagnosis of disorders suspected to be due to dental amalgam fillings. PMID- 17341884 TI - Acupuncture for perimenopausal symptoms in women who underwent oophorectomy a comparative study. AB - OBJECTIVE: To explore the effects of acupuncture on perimenopausal symptoms in women who underwent oophorectomy. METHODS: 67 women who had undergone oophorectomy were divided into an acupuncture group (n = 36) and a comparison group (n = 31) according to their wishes. The first group was treated by acupuncture and the latter group by Livial. Clinical symptoms were assessed by the modified Kupperman index. The levels of venous blood serum beta-endorphin (beta-EP), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and the maturation index (MI) of vaginal epithelial cells were assessed. RESULTS: There were no significant group differences for the MI of vaginal exfoliative cells nor for the levels of FSH, LH and E2 after treatment (p > 0.05), but Kupperman scoring and the levels of beta-EP differed significantly between the acupuncture and the Livial group (p < 0.05). No side-effects were reported in either group. CONCLUSION: Acupuncture results in a significant improvement in perimenopausal symptoms in women who have had an oophorectomy. Acupuncture performs as well or better than Livial. Yet, this result may have been influenced by a potential bias and the small sample size. PMID- 17341885 TI - Starvation and diet according to the Vinzenz Priessnitz family water book of 1847. AB - Vinzenz Priessnitz (1799-1851) did not only carry out water treatments within the scope of his cure, but also movement therapy, aerial and solar baths, natural lifestyle and, above all, diet therapy. According to the literature Priessnitz only seldom allowed starvation within his cure because this would break his preferred principle of restoration. Nevertheless, the widely unknown 'Vinzenz Priessnitz family water book' which he dictated to his daughter Sophie in 1847, includes 13 orders of starvation for a series of indications (breast inflammations, pneumonia, pulmonary embolism, cholera, intestines inflammation, tapeworm) and symptoms (diarrhoea and vomiting, heart cramp, head woe, faint, stone pains, feeling of sickness). Furthermore, it comprises diet recommendations on cold water drinking, milk and cold confection of pastry, compote and buttermilk, vegetables, fruit and strawberries, fruit and frozen food, no meat, little meat and cold food. In the view of the literature, these diet principles and means as well as their applications then and now are discussed. As for those days the Priessnitz diet was quite modern, manifold, logic and 'natural'. PMID- 17341886 TI - Elimination of xenobiotics in a female patient with fibromyalgia, chronic fatigue, and trunk obesity. AB - We describe the case of a 28-year-old woman, who had been suffering for more than 5 years from severe fatigue, myofascial pain, obstipation, obesity of trunk, abdominal striae, oedema, tinnitus, folliculitis, and facial swelling. The patient also showed a secondary adrenocortical insufficiency. From the anamnesis we assumed that environmental factors could account for the symptoms. The therapy consisted of dietary advise, chelating agents, supplements, and acupuncture. Under this therapy the patient became completely symptom-free. No such case has ever been reported before. We report mainly on the CAM diagnostic and therapeutic procedures, which are discussed together with the assumed pathogenetic factors. PMID- 17341887 TI - Insulin-like growth factors and binding proteins in early milk from mothers of preterm and term infants. AB - Breast-fed preterm infants often show a better outcome, partly ascribed to the benefit of insulin-like growth factors (IGFs) and their binding proteins (IGFBP). We compared IGF-I, IGF-II, IGFBP-2 and IGFBP-3 levels, measured by radioimmunoassays in milk samples from 30 mothers of preterm (<31 weeks) and from 19 mothers of term (>37 weeks) infants at days 7 and 21 postpartum. Proteolysis of IGFBP-2 within mother's milk and digestion of (125)I-IGF-II and (125)I-IGFBP-2 by gastric juice from neonates were assessed by electrophoretic techniques. Mean concentrations did not differ between preterm and term milk: IGF-I (2.8 +/- 0.2 vs. 2.3 +/- 0.1 ng/ml), IGF-II (12.0 +/- 0.4 vs. 12.2 +/- 0.5 ng/ml), IGFBP-3 (100.0 +/- 5.1 vs. 80.0 +/- 5.8 ng/ml), but did so for IGFBP-2 (3,144 +/- 172 vs. 2,428 +/- 188 ng/ml, p < 0.02). Immunoblots revealed 42% (p < 0.05) more IGFBP-2 fragments of 14 and 25 kDa in preterm milk. Incubation with gastric juice caused cleavage of (125)I-IGFBP-2 and partial cleavage of (125)I-IGF-II. Mutual complexation protected IGF-II and IGFBP-2 from cleavage, suggesting that both are likely to arrive in the bowel in an intact form to exert promotive effects. The results provide further evidence that IGFBP-2 and IGF-II in breast milk are relevant factors for the early development of preterm infants. PMID- 17341888 TI - Methylation status of genes upregulated by demethylating agent 5-aza-2' deoxycytidine in hepatocellular carcinoma. AB - BACKGROUND/AIMS: To determine the clinical significance of gene promoter methylation in hepatocellular carcinoma (HCC), we examined in clinical samples the methylation status of those promoters that showed elevated activity in hepatoma cell lines after 5-aza-2'-deoxycytidine treatment. METHODS: Regarding the genes with promoter hypermethylation in the cell lines, their expression levels and methylation status in HCC and non-HCC tissues were assessed by semiquantitive RT-PCR and methylation-specific PCR. To confirm the result, the expression levels and methylation status in 16 additional HCC and non-HCC tissues were assessed. RESULTS: The promoter regions of caveolin 1 (CAV1), cysteine and glycine-rich protein 1 (CSRP1), Kruppel-like factor 6 (KLF6), myosin (light polypeptide 9) (MYL9), and transgelin (TAGLN) were highly methylated in the cell lines. CAV1 and CSRP1 were methylated in HCC more frequently than in non-HCC. KLF6, MYL9, and TAGLN were fully methylated in both HCC and non-HCC. Using additional clinical samples, downregulation of CAV1 and CSRP1 was observed in 38 and 56%, respectively, of the 16 HCC samples and aberrant methylation of CAV1 and CSRP1 was observed in 56% of HCC in both cases. CONCLUSION: CAV1 and CSRP1 were inactivated in HCC by aberrant methylation and they may serve as important biomarkers of malignancy. PMID- 17341889 TI - Plausible linkage of hypoxia-inducible factor (HIF) in uterine endometrial cancers. AB - OBJECTIVE: Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with the angiogenic transcription factor hypoxia-inducible factor (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine endometrial cancers. METHODS: Sixty patients underwent curative resection for uterine endometrial cancers. In the tissue of 60 uterine endometrial cancers, HIF-1alpha, HIF-2alpha and HIF-1beta mRNA levels, and the ratio of angiopoietin (Ang)-2 to Ang-1 (Ang-2/Ang-1) mRNA levels were determined by RT real-time PCR; histochemical scores and localization of HIF-1alpha were determined by immunohistochemistry. Levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and interleukin-8 (IL-8) were determined by enzyme immunoassay. RESULTS: In stage I uterine endometrial cancers, HIF-1alpha histochemical scores and mRNA levels significantly increased with myometrial invasion of uterine endometrial cancers. HIF-1alpha histochemical scores and mRNA levels correlated with the levels of Ang 2/Ang-1 and IL-8. CONCLUSION: The angiogenic mediator HIF-1alpha, linked to Angs and IL-8, might work on angiogenesis with myometrial invasion of cancer cells in uterine endometrial cancers. PMID- 17341890 TI - Frequent occurrence of abnormal E-cadherin/beta-catenin protein expression in advanced gallbladder cancers and its association with decreased apoptosis. AB - OBJECTIVE: Our aim is to assess the clinicopathological significance of E cadherin and beta-catenin expression, as well as their association with apoptosis in gallbladder cancers. METHODS: The expression of E-cadherin and beta-catenin proteins was examined in 4 biliary tract cancer cell lines and 49 gallbladder cancer specimens by immunofluorescent or immunohistochemical methods and Western blotting. The apoptotic status was evaluated in the cell lines by poly(ADP ribose) polymerase Western blotting and in the tumors by the TdT-mediated dUTP nick end labeling assay. RESULTS: Expression of poly(ADP-ribose) polymerase (apoptosis) was only seen in cell lines that expressed both E-cadherin and beta catenin. Reduced expression of E-cadherin and beta-catenin was frequently seen in advanced gallbladder cancer cases (61 and 83%, respectively) relative to pT1 cases (25 and 63%, respectively). The 5-year survival rate in cases with reduced E-cadherin expression was 26%, significantly lower than in cases with preserved E cadherin expression (70%; p = 0.017). Cases with reduced expression of both had lower apoptotic indices and showed a worse prognosis compared with cases with reduced expression of either E-cadherin or beta-catenin (p = 0.04 and 0.049, respectively). CONCLUSIONS: The expression of E-cadherin or beta-catenin frequently diminishes as the tumor progresses, and abnormalities of E-cadherin and beta-catenin expression were associated with decreased apoptosis in gallbladder cancers. E-cadherin expression might be a useful prognostic marker in this tumor. PMID- 17341891 TI - Identification of an oligopeptide binding to hepatocellular carcinoma. AB - OBJECTIVES: We carried out identification of a small peptide binding to human hepatocellular carcinoma (HCC) cells with the aim of applying the peptide for future HCC-targeted therapy or imaging. METHODS: The biopanning technique using phage peptide display libraries was performed on HCC cells in vitro, and a phage clone expressing the HCC-binding peptide motif was selected. The binding activity of the selected phage was evaluated by plaque infection assay and immunofluorescence on cell lines. In addition, the binding activity of the peptide-expressing phage was investigated using HCC specimens derived from patients who had undergone hepatectomy for HCC. RESULTS: A heptapetide, Thr-Thr Pro-Arg-Asp-Ala-Tyr (TTPRDAY), was identified as a motif binding to HCC. TTPRDAY bound specifically to HCC cells in comparison with other cancer cells, and the binding to HCC cells was also confirmed by immunofluorescence. In addition, the synthesized TTPRDAY peptide showed binding activity and a non-mitogenic effect on HCC cells in vitro. TTPRDAY-presenting phage showed more significant binding to HCC cells derived from specimens obtained from actual patients than to non cancerous liver tissue. CONCLUSION: The motif TTPRDAY, identified by the biopanning technique, shows significant binding to HCC cells. PMID- 17341892 TI - Reversible posterior leukoencephalopathy syndrome. PMID- 17341893 TI - For small renal tumors, kidney sparing surgery provides local tumor control and prevents chronic kidney disease. PMID- 17341894 TI - Patients' choices of the place of their death: a complex, culturally and socially charged issue. PMID- 17341895 TI - Enucleoresection for the elective treatment of small renal cell carcinoma: can it be the treatment of choice? AB - BACKGROUND: We present our findings in a series of T1 renal cell carcinomas (RCC) treated with excision of the tumor surrounded by a minimal layer of grossly normal parenchyma. PATIENTS AND METHODS: A total of 43 patients who underwent elective nephron-sparing surgery performed with enucleoresection were studied retrospectively. None of the patients had preoperative or intraoperative suspicion of positive nodes and were free from distant metastases before surgery (N0, M0). Patients status was last evaluated in January 2006. RESULTS: Median age was 58.7 years (35-78). Median tumor size was 3.3 cm (1.5-7). There were no major complications such as bleeding and urinary leakage/ urinoma requiring re operation. Pathological stage was pT1a in 38 (89%), pT1b in 4 (9%) and pT3a in 1 (2%) patient. Median followup was 32 months (6-89). A total of 5 patients with RCC had died as of January 2006. Overall, 3 (6.9%) patients had disease progression, of whom 2 (4.6%) were local recurrence, 1 alone and 1 associated with distant metastases. The overall cancer-specific survival was 95.4%, and the overall progression-free survival was 93%. CONCLUSIONS: Enucleoresection reproduces the results of partial and radical nephrectomy with minimal morbidity. It is a safe and acceptable approach for elective nephronsparing surgery. PMID- 17341896 TI - Places of death from cancer in a rural location. AB - BACKGROUND: Most people would like to die at home, however, this wish still cannot be realized to any satisfactory extent. Provision of qualified palliative care can increase the death rate at home. Distribution of places of death of cancer patients in rural locations and possible factors influencing this distribution are still unknown. PATIENTS AND METHODS: We retrospectively evaluated the data relating to death certificates of cancer patients issued between 1997 and 2003 by the administrative district Sachsische Schweiz'. RESULTS: In small-town and rural locations, the places of death from cancer were equally distributed among hospital and home. Patients living in a rural location and diagnosed as having breast cancer were more likely to die at home. Since 2001, the number of breast cancer patients dying at home has been increasing. CONCLUSIONS: Rural locations provide favorable conditions for home deaths. High therapy costs and transfer of expensive therapies away from hospitals into the outpatient therapy sector appear to have an effect on the place where patients are finally cared for and where they eventually die. This circumstance meets the wishes of most patients and leads to a relevant cost saving for the healthcare system. An effective and rigorous health and economic policy is necessary in order to realize an extensive home care for terminally ill patients. PMID- 17341897 TI - Phyllodes tumors of the breast diagnostic and therapeutic dilemmas. AB - BACKGROUND: This article compares experiences in the diagnosis and treatment of phyllodes tumors from 2 regional institutions with the relevant literature. PATIENTS AND METHODS: From 1991 to 2005, 2,848 breast cancer patients were treated in our institutions, 36 (1.44%) for phyllodes tumors. The average tumor size was 5.1 cm (range 1.4-19.6). Triple assessment was the standard diagnostic algorithm. Wide excision with tumor-free margins was carried out in 29 (80.5%) cases and mastectomy in 7 (19.4%) cases. Axillary lymphadenectomy was performed in patients with positive lymph nodes. RESULTS: Histology showed the phyllodes tumors to be benign in 27 (75.0%), malignant in 6 (16.6%), and borderline in 3 (8.3%) cases. Follow-up was from 5 months to 16 years. In this period, recurrences of 3 (8.3%) malignant and 2 (5.6%) benign phyllodes tumors were diagnosed and treated. 10 (27.7%) patients treated with wide local excision showed deformities in the form of scarring. The steroid receptor status was of no prognostic value in our patients, and chemotherapy was used in only 1 (2.7%) patient. 5-year survival was 86.2%. CONCLUSION: Our study shows that tumor size, margin infiltration, mitotic activity and degree of cellular atypia are important prognostic factors. Problems in diagnosing this condition arise from its similarity to fibroadenoma. Although wide local excision is usually the treatment of choice, tumor recurrence is common. Axillary lymphadenectomy in malignant phyllodes tumors is, in our opinion, still controversial. PMID- 17341898 TI - Analysis of complications after reconstruction of bone defects involving complete mandibular resection using finite element modelling. AB - BACKGROUND: In a retrospective study, risk factors for complications after the bridging of mandibular defects using reconstruction plates were reviewed. Especially the loosening of the plate-screw-mandible complex should be analyzed with a finite element model in order to reduce plate complications in future. PATIENTS AND METHODS: We examined 60 patients who underwent a treatment with reconstruction plates after tumor resection during a period of 10 years. The problem of screw loosening was additionally reviewed by means of a finite element study, and a model for the loosening process was developed. RESULTS: Our postoperative examination showed that 26 patients suffered from complications that required an early removal of the plate. These complications were oral or extraoral plate exposures, the looseness of screws with or without plate displacement, and plate fractures. Thereby, we noticed that maxillary and mandibular areas of opposing teeth, the size of the mandible defect, and the crossing of the orofacial midline are all risk factors for plate complications. On the basis of the finite element model, a modified arrangement of the screws was derived. Hence, a new type of resection plate was established. CONCLUSIONS: By repositioning the screw holes along the long axis of the plate, the transition from tensile force to torque force of the screws in the screw-plate-bone complex can be minimized. Thereby, the complication of screw loosening will be considerably reduced. PMID- 17341899 TI - Effects of the anti-epidermal growth factor receptor antibody cetuximab on cholangiocarcinoma of the liver. AB - BACKGROUND: Cholangiocarcinoma is a malignant neoplasm arising from the biliary epithelium. The disease is notoriously difficult to diagnose and is usually fatal because of its late clinical presentation and the lack of effective nonsurgical therapeutic modalities. The overall survival rate, including in patients who underwent tumor resections, is poor, with less than 5% surviving more than 5 years. Over the past 5 years, several important studies have yielded new insight into the molecular mechanisms involved in the development and growth of these tumors. The tumor cells of the cholangiocarcinoma express an epidermal growth factor receptor which plays an important role in the pathogenesis of these tumors. CASE REPORT: A 49-year-old woman with cholangiocarcinoma of the liver developed spinal metastases. The antiepidermal growth factor receptor (anti-EGFR) antibody was used successfully in combination with radiotherapy. The response to treatment was assessed by magnetic resonance imaging and positron-emission tomography. CONCLUSION: The patient with cholangiocarcinoma had a response to cetuximab-based therapies. This may lead to another option for the treatment of hepatic cholangiocarcinoma. PMID- 17341900 TI - Ipsilateral breast carcinoma following treatment for primary breast lymphoma. AB - BACKGROUND: The breast is an unusual site for primary non-Hodgkin's lymphoma. Carcinoma in the same breast after treatment for lymphoma poses therapeutic challenges, but there is only 1 case report in Japanese, which describes this occurrence. PATIENT AND METHODS: A 59-year-old woman was diagnosed with infiltrating ductal carcinoma of the breast after receiving doxorubicinand vincristine-based chemotherapy for ipsilateral primary large cell breast lymphoma. The cancer was of high grade histology, with immunohistochemistry staining 3+ positive for HER2/neu. RESULTS: After lumpectomy and sentinel node biopsy, adjuvant paclitaxel without anthracyclines was given but had to be stopped early because of neurotoxicity. Radiotherapy to the breast was administered, and a 1-year course of trastuzumab was planned. CONCLUSION: Breast cancer can occur after breast lymphoma. For primary breast lymphoma, cumulative doses of cardiotoxic and neurotoxic drugs should be limited to 3-4 cycles of chemotherapy, using treatment protocols for stage I-II large cell lymphoma. Consolidation radiotherapy should be considered at a dose curative for microscopic breast cancer. PMID- 17341901 TI - Reversible posterior leukoencephalopathy syndrome after treatment of diffuse large B-cell lymphoma. AB - BACKGROUND: We report the case of a patient who experienced a severe neurologic complication after treatment of diffuse large B-cell lymphoma. CASE REPORT: A 62 year old patient was diagnosed with a diffuse large B-cell lymphoma and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone under prophylactic G-CSF substitution. After the second cycle she developed severe neurologic complications with generalized seizures and soporous condition. The MRI showed bilateral areas of signal hyperintensity in the subcortical and cortical regions in both hemispheres, consistent with the diagnosis of a reversible posterior leukoencephalopathy syndrome. The patient was under surveillance in intensive care, and a meticulous control of the blood pressure was performed. She fully recovered within a few days, and MRI changes normalized. Antineoplastic treatment had to be continued, and we chose a combination of rituximab, doxorubicin, etoposide, and prednisone. CONCLUSIONS: The reversible posterior leukoencephalopathy syndrome is believed to be the result of altered cerebral autoregulation with impaired blood flow control and resultant endothelial damage caused by different situations and agents. Several chemotherapy agents have been described in association with the syndrome. However, little is known about the prevalence of the syndrome and the follow-up of these patients, especially their further treatment. PMID- 17341904 TI - Smoking and health: New insights and recent developments. PMID- 17341902 TI - Role of preoperative local and distant staging in rectal cancer. AB - Preoperative imaging in rectal cancer is very important, as accurate staging determines optimal treatment strategy. In this review, imaging modalities for locoregional and distant staging in rectal cancer are discussed. For local staging, superficial tumors are best staged using endorectal US (EUS), as EUS is the most accurate modality for assessment of tumor ingrowth into the rectal wall layers. The more advanced tumors are best imaged using MRI, because MRI accurately predicts the distance from tumor to mesorectal fascia, and thus the circumferential resection margin (CRM), as well as possible invasion into surrounding organs. For the prediction of the nodal status none of the three imaging modalities - EUS, MRI and CT - can be reliably used for clinical decision making. Only MRI using lymph node specific contrast (such as ultrasmall paramagnetic iron oxide-enhanced MRI) seems promising for the detection of nodal disease. For the detection of distant metastases transabdominal ultrasound and chest X-ray are used as a primary screening tool. However, for the high prevalence group (stage III) both methods are insufficiently sensitive, and CT of the chest plus abdomen is preferred. PMID- 17341906 TI - Value of computed tomography pelvimetry in patients with a previous cesarean section. AB - A case-control study was conducted at the Department of Obstetrics and Gynaecology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia, to determine the value of computed tomography pelvimetry in patients with a previous cesarean section. Between January 1993 and December 1995, 219 pregnant women with one previous cesarean section met the criteria for vaginal birth after cesarean delivery. One hundred women had antenatal CT pelvimetry for assessment of the pelvis. One hundred and nineteen women did not have CT pelvimetry and served as control. Fifty-one women (51%) in the CT pelvimetry group delivered by cesarean section. Twenty-three women (23%) underwent elective cesarean section for contracted pelvis based upon the findings of CT pelvimetry and 28 women (28%) underwent emergency cesarean section after trial of labor. In the group who did not have CT pelvimetry, 26 women (21.8%) underwent emergency cesarean section. This was a statistically significant difference (P=0.02). There were no statistically significant differences in birthweight and Apgar scores in either group. There was no perinatal or maternal mortality in this study. Computed tomography pelvimetry increased the rate of cesarean delivery without any benefit in the immediate delivery outcomes. Therefore, the practice of documenting the adequacy of the pelvis by CT pelvimetry before vaginal birth after cesarean should be abandoned. PMID- 17341905 TI - An age- and gender-specific analysis of H. Pylori infection. AB - The objective of this study was to determine the incidence of Helicobacter pylori infection in different age and sex groups from the southern region of Saudi Arabia, and to relate the results to the high incidence of gastric cancer in this region. The carcinogenic effect of H. pylori is considered to be age-dependent. H. pylori infection early in life predisposes patients to gastric cancer. In contrast, acquisition of infection later in life leads to development of duodenal ulcer. We studied 528 consecutive endoscopic biopsies over a period from March 1995 to August 1996. The presence or absence of H. pylori was tabulated according to age and sex of the patients. Three hundred and fifty-three (67%) of 528 patients were positive for H. pylori. There were 313 males, among whom 217 (69%) were positive. There were 215 females, among whom 136 (63%) were positive for H. pylori. The presence of H. pylori in various age groups was as follows: under 16 years, 62%; 16 to 25 years, 67%; 26-35 years, 69%; 36-45 years, 67%; 46-55 years, 66%; and 56 years and above, 65%. Statistical analysis revealed no significant difference between the groups. No significant rise in the infection rate was noted from childhood to advanced age. These data support the belief that H. pylori infection was acquired early in life, leading to multifocal gastritis and thus predisposing the patients to gastric cancer later in life. However, H. pylori may not be the single agent of gastric cancer inasmuch as the infection affects both genders equally, whereas gastric cancer has a male preference. Perhaps some additional factors augment the pivotal role of H. pylori. PMID- 17341907 TI - The safety of laparoscopic cholecystectomy in sickle cell disease: An update. AB - As surgery in sickle cell patients is associated with high morbidity, this study aims to establish the safety of minimally invasive surgery in this high-risk group. Over a four-year period, 71 sickle cell patients underwent laparoscopic cholecystectomy (LC) for cholelithiasis. Five patients had asymptomatic gallstones. Preoperative gastroscopy and endoscopic retrograde cholangiography were performed in 7 and 14 patients, respectively. Forty-two patients were given simple blood transfusions, while 13 received partial exchange transfusions. The mean operative time was 80 minutes and the conversion rate was 5.6%. There were 10 (14%) postoperative complications, the majority of which were respiratory and wound-related. One patient (1.4%) died as a result of postoperative vaso occlusive crisis. The median hospital stay was 2.5 days. We believe that laparoscopic cholecystectomy is safe in patients with sickle cell hemoglobinopathy who are particularly at risk of developing pigmented gallstones. Therefore, the use of minimally invasive surgery is encouraged in any sickle cell patient undergoing operative intervention. PMID- 17341908 TI - Clinical aspects of malaria in the Asir Region, Saudi Arabia. AB - Three hundred and thirty-four cases of confirmed malaria seen in the Asir Central Hospital, Abha, in southwestern Saudi Arabia, were studied retrospectively. Two hundred and eighty-two of these (84.4%) were Saudis and the majority (72.2%) were living in the lowlands of Tihama. Transmission was found to occur throughout the year, with peaks following the rainy season and in the summer. In Saudis, falciparum malaria is more common than vivax (97.2% vs. 2.8%), while vivax malaria is more commonly seen in expatriates (46.2%). Poor response of falciparum malaria to chloroquine was more prevalent in expatriates than in Saudis (46.4% vs. 23%). Most of the expatriates gave a history of recent travel to countries known to be endemic with resistant malaria. The possibility of the emergence of chloroquine-resistant malaria in the southwestern region of Saudi Arabia was discussed. PMID- 17341909 TI - Childhood epidemiology of hepatitis A virus in Riyadh, Saudi Arabia. AB - The prevalence of anti-HAV antibody in children was tested in subjects presenting at clinics in Riyadh, Saudi Arabia. A blood sample was taken to test for the presence of IgG (indicating past infection) and a questionnaire concerning personal and epidemiological data relating to hepatitis A was completed. In total, 592 children aged 6 months to 15 years were suitable for the analysis. There were 179 subjects who were positive for HAV (30.2%). The proportions of subjects positive for HAV varied significantly with age (P=0.001); 32%-49% in the 7-15 age range were positive compared with 13-20% aged 6 and below. There was a significant association between a positive HAV test and social level (P=0.044), with a higher proportion positive in the low social level. Children with jaundice, personal history of jaundice or travel abroad were significantly more likely to be HAV positive (P=0.001, P=0.006, P=0.021, respectively). There was also a significant association with nationality (P=0.022), where the lowest proportion of HAV positive children were Saudi Arabian (28%). Compared to previous studies, there is a significant decrease in the HAV exposure in Saudi children with shift from high to intermediate pattern. National strategy for prevention should be evaluated. PMID- 17341910 TI - Benign disorders of the prostate: A histopathological study. AB - Although the medical literature contains adequate accounts of the pathophysiology of various benign prostatic disorders, it is often necessary to revisit these lesions, to reexamine the relationships between known benign lesions and more sinister, malignant disorders, in the light of new advances in our understanding of the processes. We carried out a histopathological review of prostatic surgical pathology material seen over a sevenyear period in our hospital. Our findings show that benign enlargement of the prostate or benign prostatic hyperplasia (BPH) is initially fibromuscular in many cases, becoming glandulostromal with advancing age. While we found no relationship between prostatitis and age, individual gland necrosis tended to occur relatively early and correlated well with stromal repair, which we believe forms the basis of fibromuscular hyperplasia. Epithelial hyperplasia may result from glandular regeneration, and basal cell hyperplasia, papillary hyperplasia and cribriform hyperplasia all showed significant correlation with prostatic intraepithelial neoplasia (PIN). On the other hand, only cribriform hyperplasia showed correlation with atypical adenomatous hyperplasia (AAH), and also demonstrated an increase in incidence with advancing age. Our findings underline the positive relationships between benign events such as glandular necrosis with repair and epithelial hyperplasia, which may itself predispose to recognized premalignant lesions such as PIN. PMID- 17341911 TI - Systemic antifungal therapy: Past, present and future. PMID- 17341912 TI - Surgeons and the operating theater: Past, present and future. PMID- 17341913 TI - Translation and adaptation of the revised Denver pre-screening developmental questionnaire for Madinah children, Saudi Arabia. AB - A childas development is largely connected with environment, and so tools used in developmental assessment and screening should be modified to match the local environment of children. The experience and findings of such modifications is important to child health workers. The objectives of this study were to describe the method applied in translating the Revised Denver Pre-screening Developmental Questionnaire (R-PDQ) as a developmental screening tool, and to describe and analyze changes introduced to the R-PDQ after translation, adaptation and validation for Saudi children. To adapt the R-PDQ, three steps were taken: translation from English to Arabic using cross-translation method, piloting the Arabic translation on 65 children and mothers, and conducting the questionnaire on a random sample of 1219 children to introduce final necessary changes. The English R-PDQ went through major changes to make it valid for use in Saudi culture for evaluation of a childas development. Changes were made in the content of the questionnaire, age intervals, as well as normal age of developmental abilities and the order of acquiring them. Changes in the R-PDQ items were pertinent in language and personal-social items. No major changes were introduced in fine-motor or gross-motor items. This study demonstrates a model in adapting a developmental screening tool, and illustrates the need for standardization of aimporteda developmental screening tools before using them. PMID- 17341914 TI - Postpartum collapse caused by extensive mesenteric venous thrombosis. PMID- 17341915 TI - Tarlov's cyst. PMID- 17341917 TI - Methemoglobinemia induced by accidental ingestion of nitrite. PMID- 17341916 TI - Kikuchi's disease and systemic lupus erythematosus in a Saudi child. PMID- 17341918 TI - Neonatal bladder rupture: A rare etiology. PMID- 17341919 TI - Fanconi's anemia and primary hypothyroidism. PMID- 17341920 TI - Prevalence of HBsAg and ANTI-HCV in Saudi blood donors. PMID- 17341921 TI - Sickle cell disease: Patients' awareness and management. PMID- 17341923 TI - Misperceptions about breastfeeding among Saudi female college students. PMID- 17341922 TI - Seroprevalence of Kala-Azar among humans and dogs in Yemen. PMID- 17341924 TI - Anticardiolipin antibodies in young Saudis with ischemic stroke. PMID- 17341925 TI - Acute respiratory tract infections: Epidemiological data, guided case management and outcome in a pediatric hospital in Riyadh. PMID- 17341926 TI - Parental awareness of liver disease among children in Saudi Arabia. PMID- 17341927 TI - The management of hepatic hydatid cyst cavity by overlapping. PMID- 17341929 TI - Reply. PMID- 17341928 TI - Flavobacterium meningosepticum in ICUs. PMID- 17341930 TI - Chloroquine resistance among malarial episodes in Saudi Arabia. PMID- 17341931 TI - Isolated breast lump of tuberculosis etiology. PMID- 17341932 TI - Melatonic neuroectodermal tumor of infancy in a child. PMID- 17341933 TI - Granulomatous lobular mastitis: Clinicopathological study of 12 cases. PMID- 17341934 TI - The management of acute respiratory infections: Saudi national protocol for diagnosis and treatment. PMID- 17341935 TI - Reply. PMID- 17341936 TI - Child abuse and neglect in Saudi Arabia: What are we doing and where do we stand? PMID- 17341937 TI - Child abuse and neglect: Perspective from King Faisal Specialist Hospital and Research Centre. PMID- 17341938 TI - Pattern and factors associated with glycemic control of Saudi diabetic patients. AB - BACKGROUND: The pattern and factors which can be associated with the glycemic control of Saudi adult diabetic patients were examined in this study. PATIENTS AND METHODS: Confirmed diabetic patients from all regions of Saudi Arabia constituted the study population. Random blood glucose <10 mmol/L and >10 mmol/L was used to categorize patients into good and poor glycemic control patients, respectively. RESULTS: There were 613 confirmed non-insulin dependent diabetic patients (NIDDM), 50% with good glycemic control. Patients with poor glycemic control were significantly older than patients with good glycemic control (51.5 vs. 47 years, P=0.0001). The insulin-treated diabetic population amounted to 13%, compared with 43% and 44% for oral agent and diet, respectively. The rate of insulin users among poor glycemic control diabetic population was 18%, compared with 50% for oral agents. There was a significant relationship between glycemic control and age, and treatment modalities of DM. Subjects who had good glycemic control of DM were younger and following a diet regimen, while those who had poor glycemic control were older and on insulin treatment. Multivariate analysis comprising 415 individuals was conducted to find out the factors that can potentially influence, or may be associated with, the control of DM. CONCLUSION: The association of insulin therapy with poor glycemic control is not a cause effect relationship. Insulin therapy in our study population is underutilized, given the high rate of poor glycemic control and high rate of relative occurrence of complication among the Saudi diabetic population. There is a need to address the importance of maintaining good glycemic control, and the reason for the low rate of insulin users. Close periodic monitoring of glycemic control, utilizing laboratories and home glucose monitoring devices, is required. Effective implementation of these measures, in addition to diabetes education, will have an impact on the future outcome of the Saudi diabetic population. PMID- 17341939 TI - Serum B2-microglobulin concentration correlates with urinary concentrations of type 1 collagen cross-linked N-telopeptides and deoxypyridinoline in rheumatoid arthritis. AB - BACKGROUND: Determination of serum ss2-microglobulin concentration, an invasive procedure, has been advocated for monitoring patientsA centAA response to treatment in rheumatoid arthritis. The object of this study was to find out if serum ss2-microglobulin concentration correlated with urinary excretions of type 1 collagen crosslinked N-telopeptides (NTx) and deoxypyridinoline (Pyrilinks-D) in rheumatoid arthritis (RA). SUBJECTS AND METHODS: Using chemiluminiscent assay, serum ss2-microglobulin concentrations were estimated in 25 female patients with active RA, 25 female with inactive disease, and 25 age-matched healthy female controls. Concentrations of NTx and Pyrilinks-D were also determined by immunoabsorbent assays in spot urine samples from these subject groups. RESULTS: The serum concentration of ss2-microglobulin in patients with RA (7.45+/-2.10 mg/L) was significantly higher (P<0.001) than the concentrations in patients with inactive disease (3.33+/-0.76 mg/L), or than in normal healthy controls (2.747plusmn;0.52 mg/L). Similarly, in patients with active RA, the spot urinary concentrations of NTx (123.08+/-25.53 nmol BCE/mmol creatinine) and Pyrilinks-D (15.087plusmn;3.29 nmol/mmol creatinine) were significantly higher (P<0.01) than those in patients with inactive disease (58.42AA+/-12.65 nmol BCE/mmol creatinine and 10.10+/-2.43 nmol/mmol creatinine, respectively). In patients with active RA, serum concentration of ss2-microglobulin correlated positively with spot urinary NTx concentrations (r=0.9910, P=0.0001), and Pyrilinks-D concentration (r=0.6177, P=0.001). CONCLUSION: In patients with active RA, the spot urinary concentrations of NTx and Pyrilinks-D correlated positively with serum AA2-microglobulin. Therefore, the estimations of these urinary markers may take the place of serum ss2-microglobulin estimation in monitoring the patientA centAAs response to treatment in rheumatoid arthritis. PMID- 17341940 TI - Role of endoscopic retrograde cholangiopancreatography before and after laparoscopic cholecystectomy. AB - BACKGROUND: While the role of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) in the diagnosis and management of choledocholithiasis is well established, this study evaluates the usefulness of ERCP and EST in patients with symptomatic cholecystolithiasis and suspected choledocholithiasis before undergoing laparoscopic cholecystectomy (LC), and the role of ERCP-EST in the management of complications resulting from LC. MATERIALS AND METHODS: This paper reviews retrospectively our experience from 1992 to 1995. A total of 1221 LCs and 717 ERCPs were performed, out of which 257 ERCPs were performed on 225 patients who underwent LC (230 ERCPs before and 27 after). The age range was 10-85 years (mean 43.5). The study group comprised 148 females (66%) and 77 males (34%). RESULTS: The overall success rate for ERCP was 92% (96% for diagnostic and 88% for therapeutic). Choledocholithiasis was found at preoperative ERCP in 45% of cases. Prediction of choledocholithiasis was accurate in 46%, based on abnormal liver chemistry, and 70% when based on a combination of abnormal liver tests and dilated main bile duct (>7 mm) by ultrasound. In 40 cases of acute biliary pancreatitis, choledocholithiasis was found at ERCP in eight cases (20%). In the post-LC group, all eight cases with residual stones and seven of eight cases with bile leaks were successfully treated endoscopically. There were four cases with major duct injuries that required surgical management. The complications related to ERCP-EST included two cases of bleeding post-EST (one was controlled with injection therapy and the second one was managed surgically), and three cases of mild pancreatitis. CONCLUSION: ERCP and EST are effective and safe in the diagnosis and management of choledocholithiasis, and facilitate LC for symptomatic cholelithiasis. The procedures are also valuable in the diagnosis and management of most complications resulting from LC. PMID- 17341941 TI - Wolman's disease: The King Faisal Specialist Hospital and Research Centre experience. AB - BACKGROUND: Wolman's disease is a rare autosomal recessive lysosomal storage disease. A recent review indicates that approximately 50 patients have been reported in the world. Reports of patients from the Arabian peninsula are rare due to lack of awareness among pediatricians. PATIENTS AND METHODS: We retrospectively reviewed the clinical, radiological, biochemical and histopathological findings of four Saudi patients diagnosed with Wolman's disease at King Faisal Specialist Hospital and Research Centre. The diagnosis was confirmed by deficient acid lipase activity in the leukocytes and fibroblasts, which was measured using 4-methylumbelliferyl palmitate. RESULTS: All patients were failing to thrive with progressive hepatosplenomegaly. Abdominal x-ray revealed calcifications which were confirmed on abdominal CT scan. Peripheral blood film showed vacuolated lymphocytes and the bone marrow aspiration showed foamy histiocytes. Liver biopsy in one patient showed marked steatosis and elliptical empty clefs predominantly in the Kupffer cells, indicating cholesterol storage in the reticulo-endothelial cells. The acid lipase activity was less than 6% in all patients. CONCLUSION: In all suspected cases of Wolman's disease, a plain abdominal x-ray should be obtained to check for the typical pattern of adrenal calcification characteristic of the disease, especially in any young infant with failure to thrive and progressive hepatosplenomegaly. PMID- 17341942 TI - The spectrum of child abuse presenting to a university hospital in Riyadh. AB - BACKGROUND: Child abuse is prevalent worldwide, although it is often underreported. we describe the pattern of child abuse and neglect presenting to the emergency room of our hospital, the sociocultural changes which brought this about, and suggest ways to deal with this emotionally sensitive issue. PATIENTS AND METHODS: Thirteen cases of child abuse and neglect were seen in the emergency room of King Khalid University Hospital over a period of one year from July 1996 to June 1997. There were four cases of non-accidental injury, three of which had serious injury. There were three cases of sexual abuse, four cases of neglect, resulting in the death of one child and severe emaciation in another. There was one suspected case of Munchausen syndrome by proxy, and one case of child labor with neglect. CONCLUSION: Public awareness of the problem of child abuse has increased, and recent media reports reflect the significance accorded to the issue. As more information is obtained on this subject and policies and guidelines are set in place, efforts at reporting and preventing physical and psychological trauma will gather momentum. PMID- 17341943 TI - Pharyngolaryngo-esophagectomy with immediate gastric pull-up. AB - BACKGROUND: This paper documents our experience with patients who underwent laryngopharyngoesophagectomy with immediate gastric pull-up procedures. PATIENTS AND METHOD: Fifteen patients with carcinoma of the hypopharynx and cervical esophagus underwent total laryngopharyngo-esophagectomy with immediate gastric pull-up procedures over a period of nine years at the Asir Central Hospital in the southwestern region of Saudi Arabia. RESULTS: The most common complication was cervical fistula, which with its sequelae occurred in 40%. Postoperative function in terms of swallowing ability was good but rehabilitation of speech was poor. The overall hospital mortality was 7%, and the crude survival rate was 40%. The most common cause of long-term failure was the recurrence of the disease. CONCLUSION: The success of this operative procedure depends on wide surgical excision of cancer along with rapid reconstruction of alimentary canal. PMID- 17341944 TI - Thrombocytopenia during pregnancy. PMID- 17341946 TI - Recurrence of tubulovillous adenomata following protolectomy for adenomatous polyposis. PMID- 17341945 TI - The need for continuing medical education in the Kingdom of Saudi Arabia. PMID- 17341947 TI - Mixed osteoclastic and pleomorphic giant cell carcinoma of the pancreas. PMID- 17341948 TI - Normal short synacthen test in patients with secondary adrenal failure. PMID- 17341949 TI - Primary antiphospholipid syndrome presenting as Budd-Chiari syndrome. PMID- 17341950 TI - Stiff-man syndrome. PMID- 17341951 TI - Glutaric acidemia type 1: First Saudi patient diagnosed by tandem mass spectrometry-based neonatal screening. PMID- 17341952 TI - An unusual presentation of a retained esophageal foreign body. PMID- 17341953 TI - Sjogren's syndrome presenting with hypokalemic paralysis due to renal tubular acidosis. PMID- 17341955 TI - Corrosive burns of the upper gastrointestinal tract among Jordanian children. PMID- 17341954 TI - Insecticide/organophosphrus compound poisoning in children. PMID- 17341956 TI - Blood stream infections: micro-organisms, risk factors and mortality rate in Qatif Central Hospital. PMID- 17341957 TI - Acute abdomen in pregnancy: Are tocolytics and early surgical intervention justified? PMID- 17341958 TI - Aplasia cutis congenita: A report of five cases in Riyadh. PMID- 17341959 TI - Cancer patients' awareness of their disease and prognosis. PMID- 17341960 TI - Adverse reaction to heparin products: A case report. PMID- 17341962 TI - Ectopic thymus presenting as a neck swelling in a newborn. PMID- 17341961 TI - The arteries in tuberculosis. PMID- 17341963 TI - Reply. PMID- 17341964 TI - Doxycycline-induced esophageal ulceration. PMID- 17341965 TI - Tobacco or health: A global status report. PMID- 17341966 TI - Towards a campaign to combat psychological disorders in the community. PMID- 17341967 TI - Outcome of in-hospital pediatric cardiac arrest. AB - BACKGROUND: The outcome of pediatric cardiac arrest is poor, and attempts to improve it have not been very successful. The aim of this study was to analyze the outcome of a large number of in-hospital pediatric cardiac arrest patients, and to determine the factors that influence this outcome. PATIENTS AND METHODS: The records of hospital inpatients at King Faisal Specialist Hospital and Research Centre who received external cardiac massage as part of their cardiopulmonary resuscitation were reviewed. Success of resuscitation was analyzed as: 1) short-term (restoration of spontaneous circulation); and 2) long term (discharge from hospital). RESULTS: Of 234 such patients, 171 (73.1%) survived the initial resuscitation, and 66 (28.2%) were discharged from hospital. Success of outcome was not related to age, time of day, or location of arrest. Longer resuscitation time was associated with less chance of restoration of spontaneous circulation (P<0.001), and lower hospital discharge rate. RESULTS for patients with congenital heart disease were similar to those with other medical or surgical conditions. Restoration of spontaneous circulation from asystole was more difficult when compared to other arrest rhythm, but once circulation was restored, long-term outcome was not influenced by rhythm. CONCLUSION: Asystole and longer resuscitation time are associated with poorer outcome, however, successful restoration of spontaneous circulation with long-term survival can be achieved after prolonged resuscitation. PMID- 17341968 TI - Smoking habits of King Saud University students in Abha, Saudi Arabia. AB - BACKGROUND: The aim of this study was to estimate the prevalence of smoking among university students of King Saud University in Abha City, to determine ecological factors for the problem, and to assess the studentsa knowledge about the health effects of smoking, and attitudes towards public action against smoking. MATERIALS AND METHODS: All medical students at the University College of Medicine (MC) (n=202), and a representative sample of students of the College of Education (CE) (n=300), were subjected to a modified Arabic version of the World Health Organization standard questionnaire for young people to study their knowledge, attitudes and practices of smoking. RESULTS: The study revealed the following results among students of the CE and those of the MC, respectively. Prevalence of regular smoking (17.5% vs. 13.6%; P=0.25); heavy smokers (39.5% vs. 27.8%; P=0.38); smokers of moderate- to high-nicotine yield (92.7% vs. 50%, P=0.0004), and tar yield (48.8% vs. 16.7%, P=0.02). Curiosity was the main reason for initiation of smoking (41.2% vs. 51.9%), followed by the desire to show off (27.5% vs. 51.9%, P=0.03), and peer pressure (27.5% vs. 7.4%, P=0.04). Friends were the main source of the first cigarette (53.1% vs. 55.6%), followed by parents (2% vs. 40.7%, P=0.0001). Most students were knowledgeable about smoking and had favorable attitudes against it. However, MC students were significantly more knowledgeable than those of the CE. CONCLUSION: Smoking still constitutes a major problem among university students in Abha, in spite of their knowledge of its hazards. This may be due to the addictive effect of smoking, peer pressure, negative parental attitudes and other reasons. There is a need to implement an anti-smoking program for college students, and possibly legislation to limit the amount of tar and nicotine in cigarettes. PMID- 17341969 TI - Sonographic assessment of spleen size in Saudi patients with sickle cell disease. AB - BACKGROUND: In patients with SCD, the spleen commonly enlarges during the first two decades of life but then undergoes autosplenectomy due to repeated attacks of vaso-occlusion and infarction. This, however, is not the case in Saudi patients with SCD, where splenomegaly sometimes persists into adult life. PATIENTS AND METHODS: Ultrasonography was used to evaluate spleen size in 363 Saudi patients with SCD (340 SCD and 23 sickle I(2)-thalassemia). A total of 363 patients were evaluated. Their ages ranged from 1-60 years (mean 16 years). RESULTS: Only 24 (6.6%) of our patients had autosplenectomy. The splenic index increased with age until about 40 years of age and then gradually decreased, indicating persistence of splenomegaly in our patients into an older age group. Forty-three patients (11.8%) had marked-massive splenomegaly (splenic index >120 cm 2) and these had higher HbF levels (mean HbF=22.2%) when compared with those who had autosplenectomy (mean HbF=14.6). This is significant (P-value=0.0169) and confirms the effect of HbF on persistence of splenomegaly in SCD patients. CONCLUSIONS: Ultrasonography is a simple, safe and accurate method of assessing splenic size in patients with sickle cell disease. Patients with persistent splenomegaly should be followed closely for development of complications which may necessitate splenectomy. PMID- 17341970 TI - Adult acute myeloblastic leukemia: Experience at King Khalid University Hospital. AB - BACKGROUND: The clinical features of acute myeloblastic leukemia (AML) and its response to therapy in adult patients in Saudi Arabia are not well defined, as only scanty data has been available. This situation will likely continue unless experience with AML is reported from different institutions in the Kingdom. PATIENTS AND METHODS: In this retrospective study, the records of 52 adult patients with previously untreated de novo acute myeloblastic leukemia (AML) who were treated at King Khalid University Hospital over a five-year period from January 1989 to December 1993 according to the conventional a3+7a regimen were reviewed. The clinical features of the disease, response to therapy and treatment related complications were identified. RESULTS: There were 33 males and 19 females with a mean age of 30+/-13 years (mean+/-SD). M 4 and M 5 AML were the predominant French-American-British (FAB) subtypes encountered. Sixty-five percent of patients achieved complete remission (CR). The median duration of the first CR of all analyzable patients was 32 weeks. The median CR duration and survival of patients achieving complete remission who survived through their consolidation treatment was 36 and 49 weeks, respectively. CONCLUSION: Both median duration of the first complete remission and survival compare unfavorably with those reported in the literature despite a comparable remission rate. Infectious complications were frequent and accounted for a significant number of mortalities. PMID- 17341971 TI - The prevalence of endoscopic esophagitis in duodenal ulcer patients and symptomatic controls. AB - BACKGROUND: A large series of duodenal ulcer patients was examined in order to determine the prevalence rate of reflux esophagitis and compare it to that of a series of symptomatic controls, as well as to find out if complicated duodenal ulcer patients are at a higher risk of developing reflux esophagitis. PATIENTS AND METHODS: All consecutive patients attending the Endoscopy unit between January and December 1996 who were found to have duodenal ulcers were prospectively recruited for this study. Consecutive patients with upper abdominal symptoms but negative gastroscopy for duodenal ulcers were used as a control. Patients known to have reflux esophagitis, those on peptic ulcer treatment for more than a week, those with dysphagia as a presenting symptom or underlying upper gastrointestinal malignancy, and patients who had undergone previous ulcer surgery were excluded from the study. A hundred and forty-one patients were found to have duodenal ulcer (Group I), and one hundred and seventy-two served as a control (Group II). The two groups were matched for age, NSAID ingestion and smoking habit. However, Group I included significantly more patients with underlying co-morbid conditions and fewer females. RESULTS: The prevalence of reflux esophagitis was similar between both groups, 30.5% vs. 38.4%, P=0.18. Furthermore, bleeding duodenal ulcer patients (sub-group III) were compared to non-bleeding duodenal ulcer patients (sub-group IV). Although Group III included significantly more smokers, NSAID ingestion and comorbid conditions, there was no significant difference in the prevalence rate of reflux esophagitis, P=0.13. Moreover, 92.7% of afflicted patients suffer mild or moderate esophagitis. CONCLUSION: Endoscopic esophagitis is a frequent finding in both duodenal ulcer and control subjects. PMID- 17341972 TI - Saudi experience with classic homocystinuria. AB - BACKGROUND: Classic homocystinuria is an autosomal recessive disorder due to cystathionine ss-synthase deficiency. The clinical, radiological and neurophysiological findings of classic homocystinuria diagnosed at King Faisal Specialist Hospital and Research Centre (KFSH&RC) are presented in this report. PATIENTS AND METHODS: Twenty-four patients (15 females and 9 males) were referred to KFSH&RC for work-up of mental retardation, seizures, thrombo-embolic episodes and dislocation of the ocular lenses. RESULTS: The common clinical findings included ectopia lentis (20 patients), skeletal system involvement (18 patients), vascular system involvement (9 patients), and mental retardation (all patients to varying degrees). Unusual findings consisted of a patient who developed severe lower gastrointestinal bleeding, a patient with insulin-dependent diabetes mellitus, probably due to vasculopathy, and another having severe bronchiectasis, which may have been due to fibrillin disruption, and required the resection of a lobe of the lung. The parents of 21 patients were first-degree relatives, and 19 patients had one or more family members affected by the same disease. All patients had markedly elevated plasma levels of methionine. Cystathionine synthase activity in the fibroblast was measured in 25% of the patients and was deficient. Only four patients responded to pyridoxine and their methionine level decreased to almost normal range. CONCLUSION: The aim of this study was to increase the awareness of this disease in the scientific and medical community, in particular in the general pediatrician working in Saudi Arabia who first encounters the clinical manifestations of the disease. Early detection through tandem mass spectrometry of blood spot screening and treatment are important, and may prevent the major complications of this disease. PMID- 17341973 TI - Diagnosis of inborn errors of metabolism by tandem mass spectrometry. PMID- 17341974 TI - Thyrocervical trunk pseudoaneurysm. PMID- 17341975 TI - An unusual implantation of a rectosigmoid andenocarcinoma into a hemorrhoidectomy scar. PMID- 17341976 TI - Hypervitaminosis D: Report on three patients. PMID- 17341977 TI - Laparoscopic cholecystectomy in situs viscerum inversus totalis. PMID- 17341978 TI - Abdominal port seeding after laparoscopic nephroureterectomy for transitional cell carcinoma. PMID- 17341979 TI - Spontaneous recovery of spinal epidural hematoma. PMID- 17341980 TI - Immature teratoma of the thyroid gland: A case report and review of the literature. PMID- 17341981 TI - Oral and upper aero-digestiive tract malignancy: A review of a five-year experience. PMID- 17341982 TI - Congenital hernia of morgagni in children. PMID- 17341983 TI - Protective factors in posterior urethral valves in Saudi children. PMID- 17341984 TI - Experience of concomitant splenectomy and cholecystectomy in patients with sickle cell disease. PMID- 17341985 TI - The "unbooked mother" at a university teaching hospital: Factors mitigating against antenatal clinic attendance. PMID- 17341986 TI - Viral hemorrhagic fever: Admission policy for hospitals in the Arabian Peninsula. PMID- 17341987 TI - Missed odontoid process fracture in children. PMID- 17341988 TI - Maffucci's syndrome. PMID- 17341989 TI - Operative cholangiography in laparoscopic cholecystectomy: Is it essential? PMID- 17341992 TI - New antihypertensive agents: will they work in blacks? PMID- 17341993 TI - Effects of valsartan or amlodipine alone or in combination on plasma catecholamine levels at rest and during standing in hypertensive patients. AB - To compare the effects of valsartan and amlodipine alone or in combination on plasma norepinephrine (NE) at rest and standing for 10 minutes in patients with hypertension, 47 patients with a sitting diastolic blood pressure (BP) (DBP)>95 mm Hg and<110 mm Hg were randomized in a double-blind fashion to either valsartan or amlodipine. During the first 4 weeks of treatment, patients received a low dose of either valsartan (80 mg) or amlodipine (5 mg). The patients were force titrated to the high dose of either drug (160 or 10 mg) for 4 weeks. After 8 weeks of therapy, those who still had a DBP>90 mm Hg (nonresponders) received combination therapy with the other drug, whereas patients with a DBP<90 mm Hg (responders) continued on monotherapy. Decreases in ambulatory BP and clinic systolic BP and DBP were significant (P<.05) after 8 weeks' therapy with no difference between the 2 groups. Amlodipine but not valsartan as monotherapy consistently increased NE levels at rest and enhanced NE levels during standing. Valsartan decreased basal NE in responders. Combination therapy with valsartan and amlodipine did not attenuate the rise in NE levels induced by amlodipine. This study indicates that therapy with amlodipine increases peripheral sympathetic basal tone and reactivity to standing in patients with hypertension, whereas valsartan does not. Combined therapy with amlodipine/valsartan did not attenuate the sympathetic activation induced by amlodipine. The hypotensive action of valsartan may be mediated in part by an inhibition of the sympathetic baroreflex in patients with hypertension. PMID- 17341994 TI - Comparison of increasing doses of olmesartan medoxomil, losartan potassium, and valsartan in patients with essential hypertension. AB - This 12-week, randomized, double-blind, forced-titration study compared the efficacy of 3 angiotensin receptor blockers. Patients received olmesartan medoxomil 20 mg, losartan potassium 50 mg, valsartan 80 mg, or placebo once daily. At week 4, doses were titrated to 40, 100, and 160 mg once daily for olmesartan, losartan, and valsartan, respectively. At week 8, losartan was increased to 50 mg twice daily and valsartan increased to 320 mg once daily (olmesartan remained at 40 mg once daily). The primary end point was mean change from baseline in seated diastolic blood pressure (SeDBP) at week 8. All 3 medications significantly reduced mean SeDBP from baseline compared with placebo at weeks 4, 8, and 12 (P<.001). At week 8, olmesartan reduced mean SeDBP more than losartan (P<.001); more patients in the olmesartan medoxomil group achieved a blood pressure goal of <140/90 mm Hg (P<.001). Olmesartan did not reduce mean SeDBP significantly compared with valsartan, although more patients attained blood pressure goal with olmesartan (P=.031). At week 12, all agents lowered blood pressure equivalently. PMID- 17341995 TI - Microalbuminuria: what is it? Why is it important? What should be done about it? An update. AB - Microalbuminuria (MA) is defined as a persistent elevation of albumin in the urine of >30 to <300 mg/d (>20 to <200 microg/min). Use of the morning spot urine test for albumin-to-creatinine measurement (mg/g) is recommended as the preferred screening strategy for all patients with diabetes and with the metabolic syndrome and hypertension. MA should be assessed annually in all patients and every 6 months within the first year of treatment to monitor the impact of antihypertensive therapy. It is an established risk marker for the presence of cardiovascular disease and predicts progression of nephropathy when it increases to frank microalbuminuria>300 mg/d. Data support the concept that the presence of MA is the kidney's warning that there is a problem with the vasculature. The presence of MA is a marker of endothelial dysfunction and a predictor of increased cardiovascular risk. MA can be reduced, and progression to overt proteinuria prevented, by aggressive blood pressure reduction, especially with a regimen based on medications that block the renin-angiotensin-aldosterone system, and control of diabetes. The National Kidney Foundation recommends that blood pressure levels be maintained at or below 130/80 mm Hg in anyone with diabetes or kidney disease. PMID- 17341996 TI - Renal artery stenosis and cardiovascular risk. AB - Atherosclerotic renal artery stenosis is the most common disease of the renal arteries and may lead to ischemic renal disease and hypertension. A close relationship exists between renal and cardiovascular disease, as they often occur concomitantly, and abnormalities in either system can cause disease and determine clinical outcome in the other. Renovascular disease is gaining recognition as a potentially important risk factor for cardiovascular morbidity and mortality. This article explores the association between atherosclerotic renal artery stenosis and the cardiovascular system. PMID- 17341997 TI - The nonpharmacologic treatment of hypertension: how effective is it? An update. AB - Following a hypertension symposium in Los Angeles, CA, in October 2006, a panel was convened to update information about lifestyle changes or the nonpharmacologic treatment of hypertension. Dr Marvin Moser, Clinical Professor of Medicine at the Yale University School of Medicine, moderated the panel. Dr Stanley S. Franklin, Clinical Professor of Medicine and Associate Medical Director of the Heart Disease Prevention Program at the University of California, Irvine, and Dr Joel Handler, Director of the Orange County Kaiser-Permanente Hypertension Clinic and clinical hypertension leader of the Care Management Institute of Kaiser Permanente, participated in the discussion. PMID- 17341998 TI - Genetics and hypertension. AB - Although it has long been appreciated that there is a genetic component to hypertension, it is only recently that specific genes are being identified. This progress is part of a general advancement of our understanding of common, genetically complex human diseases. This understanding will eventually affect clinical practice. PMID- 17341999 TI - Morning hypertension. PMID- 17342000 TI - Frequency and predictors of return to incentive spirometry volume baseline after cardiac surgery. AB - Incentive spirometry (IS) is routinely used in most clinical settings, but evaluation of patient efficacy of IS is not standardized. The purpose of this study was to describe the degree and predictors of return to preoperative IS volume after cardiac surgery. IS volumes were documented in 69 subjects (71% men; mean age, 59 years) undergoing cardiac surgery during the preoperative evaluation and twice daily postoperatively. Nineteen percent of subjects achieved their IS preoperative volume by hospital discharge. Based on highest volume achieved, subjects achieved an average of 75% of their preoperative volume by discharge, and only age and number of bypass grafts predicted return to preoperative IS volume. These data may assist nurses and patients to set realistic goals for postoperative IS volume achievement. PMID- 17342001 TI - Black, Hispanic, and white women's perception of heart disease. AB - Understanding why women delay seeking treatment for symptoms suggestive of an acute myocardial infarction remains elusive. Thirty individual semistructured interviews were conducted to determine black (n=10), Hispanic (n=10), and white (n=10) women's perception of heart disease risk and whether differences existed based on participant's race or ethnicity. Narrative descriptions analyzed using the Morse and Field method revealed that women, regardless of race or ethnicity, associated heart disease and heart attacks with men who were obese, stressed, and smokers. Perceptions of heart disease risk were similar between groups, with women generally believing they were at risk for heart disease because of family history, diet, and obesity. Racial and ethnic differences were noted, however, in risk reduction and anticipated treatment-seeking behaviors. Continued efforts are needed to raise women's perception of their cardiac risks and the need for the engagement in health-promoting behaviors. PMID- 17342003 TI - The dangers of cardiac myxomas. AB - A variety of cardiac tumors have been acknowledged in the literature since the 16th century as rare forms of cardiac disease. Of the primary tumors, myxomas account for at least 30% to 50% of benign tumors. Despite significant advances in cardiac diagnostics leading to early recognition of myxomas, the potential for deleterious effects secondary to embolic complications remains high. The purpose of this paper is to provide nurses with an understanding of the epidemiology, pathology, clinical presentation, and assessment of individuals with cardiac myxomas. A case presentation is used to illustrate how the misdiagnosis of cardiac myxoma led to a delay in patient treatment. Prompt recognition, diagnosis, and treatment are important in improving patient outcomes and quality of life. Due to the infrequency of cardiac myxomas, ensuring appropriate preoperative and postoperative nursing care to the patient with a cardiac myxoma is essential. PMID- 17342002 TI - Evaluation of a Web-based education and counseling pilot program for older heart failure patients. AB - Web-based communication has been reported as a feasible management tool for heart failure (HF) patients and has also been documented to positively impact quality of life (QOL). The feasibility and effectiveness of a Web-based educational and HF management program among older HF patients (60 years and older), however, have not been previously explored. Therefore, a prospective study was conducted. QOL (physical and mental health) and perceived control (PC) scores of 40 participants were measured (baseline and 3 months) and retrospectively compared with an age- and sex-matched control group of 40 patients receiving HF care as usual. Between group differences over time were statistically significant in the QOL mental health component and PC scores. The authors' findings demonstrate the beneficial effects of a Web-based program on QOL and PC in older patients with HF. This approach may be potentially beneficial in delivering educational and behavioral support to this high-risk group in ways that are affordable and accessible. PMID- 17342004 TI - Current endovascular treatment of peripheral arterial disease. AB - Atherosclerotic peripheral arterial disease is a common medical problem worldwide and portends a poor prognosis because of increased cardiovascular morbidity and mortality. Regular exercise, weight loss, and aggressive risk factor modification, including treatment of dyslipidemia and complete cessation of smoking, is extremely important in this high-risk cohort. Vascular surgery in these patients, who often have concomitant coronary or cerebrovascular atherosclerosis, is associated with significant risk. Steady improvements in endovascular revascularization techniques have made this a safe and effective alternate revascularization modality. Percutaneous peripheral vascular interventions have increased dramatically in recent years, from 90,000 in 1994 to more than 200,000 in 1997, and endovascular techniques may soon replace up to 50% of traditional vascular operations. In this article, the authors review the current state of interventional treatment for peripheral arterial disease. PMID- 17342005 TI - Sleep disturbances in caregivers of patients with end-stage congestive heart failure: Part I--The problem. AB - Up to 90% of caregivers report sleep disturbances, particularly congestive heart failure (CHF) caregivers. Sleep disturbances have numerous consequences that can negatively impact a wide domain of outcomes in both the caregiver and the patient for whom they care. Ultimately, these disturbances can lead to caregiver morbidity and CHF patient morbidity, readmission, and mortality. Nurses play a central role in patient education, especially with caregivers. Therefore, nurses can help to educate caregivers on the consequences of stress-related sleep disturbances, which are very prevalent in CHF caregivers. PMID- 17342006 TI - Dietary sodium in heart failure: what to tell your patients. PMID- 17342007 TI - Cardiovascular nursing in Belgium: at the crossroad. PMID- 17342008 TI - Angiotensin-converting enzyme inhibitor-related angioedema: recognition and treatment. PMID- 17342009 TI - Preventricular contractions or preexcitation? PMID- 17342010 TI - Observational studies can help fill important gaps in understanding and treating cardiovascular disease in the elderly. PMID- 17342011 TI - Deactivation of advanced lifesaving technologies. PMID- 17342013 TI - Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. PMID- 17342012 TI - A coronary artery fistula with aneurysm draining into the coronary sinus: role of transesophageal echocardiography. PMID- 17342014 TI - Four levels of block. PMID- 17342015 TI - Wound infection: facts to face. PMID- 17342016 TI - Caricatures in medicine and dermatology--an underutilized tool. PMID- 17342017 TI - Trichorrhexis nodosa revisited. PMID- 17342018 TI - Clinical pearl: a flea trap made from common household supplies. PMID- 17342019 TI - From the inside out: the Moisturol story could have taken another twist. PMID- 17342020 TI - Bullous dermatoses in childhood: part I. AB - A classification of bullous dermatoses in childhood is presented, according to the histologic location of the bulla and the heritability of the disease, combined with the most recent laboratory examinations used in dermatologic practice. For a better understanding of the proposed classification, the authors also present a review of this group of diseases, which vary greatly within the group. In this first part of the classification and review, the group of bullous dermatoses with nonhereditary characteristics and intraepidermal cleavage is described. PMID- 17342021 TI - Ziana (clindamycin phosphate 1.2% and tretinoin 0.025%)gel. PMID- 17342022 TI - Drinking 6 to 8 glasses of water a day is essential for skin hydration: myth or reality? PMID- 17342023 TI - Sexual health medicine, 2007. AB - For 2007, this series will focus on concepts in sexual health, with special emphasis on the human immunodeficiency virus/acquired immunodeficiency syndrome; bacterial sexually transmitted infections, such as chlamydia, gonorrhea, lymphogranuloma venereum, and syphilis; and changing concepts in viral conditions, such as immunization against human papilloma virus. The current article focuses on sexual health in its entirety. PMID- 17342025 TI - A simple diagnostic screening test for children with short stature - with emphasis on genetic defects along the GH axis. PMID- 17342026 TI - Prenatal diagnosis and treatment of congenital adrenal hyperplasia. AB - Congenital adrenal hyperplasia (CAH) is a group of inherited disorders caused by enzyme deficiencies in steroid biosynthesis, which disrupt the conversion of cholesterol to cortisol. The most common form of CAH is 21-hydroxylase deficiency (21-OHD). In its severe form, 21-OHD causes prenatal virilization of external female genitalia. Through molecular genetic analysis of fetal DNA, defects in 21 OH synthesis can be diagnosed in utero. Genital ambiguity in females can be reduced or eliminated with prenatal dexamethasone treatment, which successfully suppresses fetal androgen production. Data from current, large cohort studies show that prenatal diagnosis and treatment are safe and effective. PMID- 17342027 TI - Cortistatin - a new neuroendocrine hormone? AB - Cortistatin (CST) is a recently described neuropeptide. Although the expression of CST was initially reported to be restricted to the rat cerebral cortex and hippocampus, it is currently known to have wide distribution in many human organs. CST shares high homology with somatostatin and binds with high affinity to all somatostatin receptor (SSTR) subtypes. Indeed, many of its endocrine and biological activities overlap with somatostatin. However, CST and somatostatin are expressed in only partially overlapping cortical neuron populations. They are regulated by different stimuli, their cortical actions are diverse and CST, at variance with somatostatin, was shown to have a possible role in the human immune system. The activities specific to cortistatin may be attributable to its unique binding to the GH secretagogue (GHS) receptor (GHS-R) and the orphan G-protein coupled receptor, MrgX2, which is not shared by somatostatin. The potential biological roles and therapeutic use of CST and the receptors involved in its action require further investigation. PMID- 17342028 TI - Endocrine effects on the growth, development and function of the eye. AB - A cohort of hormonal signals affects the function of the eye in providing eyesight. From the early days of growth, endocrine mechanisms guide the young eye's development. Later on in life, hormonal interactions play an important role in maintaining proper vision and continue to affect the eyes in pregnancy, as well as in aging. The purpose of this article is to review the effects of the endocrine system on the eye. Current knowledge about hormonal interactions that play a role in the growth and development of the eye will be discussed separately for each of the hormones known to be involved. PMID- 17342029 TI - The clinical diagnosis and molecular genetics of kearns-sayre syndrome: a complex mitochondrial encephalomyopathy. AB - From the first description by Kearns and Sayre in 1958, this syndrome has been diagnosed in several hundred patients. However, the labile character of its clinical manifestations makes diagnosis difficult and delayed. Only recently, some thirty years from the first diagnosis, have we recognized mitochondrial DNA rearrangements as the molecular basis of the disease. This has lead to increasing interest in the contribution which mtDNA deletions make to Kearns-Sayre Syndrome (KSS) and other disorders. Although the true prevalence of this syndrome in the general population is unknown, a basic awareness of the KSS phenotype, as well as of the essential elements of patient evaluation is important for appropriate patient management. Although methods of assessing patients for mtDNA rearrangements are well developed, ambiguity in patient diagnosis often remains even after detailed, multisystem testing. Advances in our understanding of the genetic background and the tissue specific effects of mtDNA deletions, in addition to resolving the inheritance pattern, will also increase our ability to diagnose, manage and counsel patients with this disorder. PMID- 17342030 TI - The molecular basis of diabetic microangiopathy. AB - Diabetes mellitus is a chronic disease characterized by hyperglycaemia and carbohydrate, fat and protein metabolism abnormalities, all due to an impairment in insulin homeostasis and a diffuse microangiopathy most involving retina, kidney and nerves. Several mechanisms are altered at a molecular level and interplay to develop the slow but devastating clinical impairments related to microangiopathy. Polyol pathway, advanced glycation endproducts, protein kinase C, hexosamine pathway and oxidative stress are among those mechanisms. Molecular pathways of diabetes from hyperglycaemia to signalling cascades alterations and the most promising strategies for successful therapeutic approaches derived from better knowledge of biochemical mechanisms are treated extensively in the present review. PMID- 17342031 TI - The Sixth ESPE Growth Plate Working Group Symposium (EUROGROP), June 30th, Rotterdam, the Netherlands, "a multidisciplinary approach to growth plate biology". PMID- 17342032 TI - Report of the 31st European Thyroid Association (ETA) annual meeting, held in Naples-Italy 2-6 September 2006. PMID- 17342033 TI - First International Conference on Therapies of Obesity: perspectives for pharmaceutical and natural products (Paris Anti Obesity Therapies 2006), May 18 19 2006, Institut Pasteur, Paris, France. PMID- 17342034 TI - Classic and endovascular surgical management of isolated iliac artery aneurysms. AB - AIM: Isolated iliac artery aneurysm is a rare pathology that is often asymptomatic for long periods; this late diagnosis exposes patients to a high risk of death following aneurysm rupture. The aim of this study was to establish the most suitable diagnostic approach, the correct indications for treatment, and the most appropriate tactics and surgical technique. METHODS: Twenty-eight patients were observed over 13 years. Aneurysmal involvement was unilateral in 22 cases and bilateral in the remaining 6 patients. Preoperative diagnostic tests included eco-colour Doppler (ECD) and angio-CT in all cases, with angio-MR and angiography as more selective procedures. Seventeen patients underwent conventional open surgery with prosthetic replacement of the aneurysmatic tract, 7 patients were treated using endovascular exclusion, and lastly 4 were monitored over time. RESULTS: There was no perioperative mortality for either treatment. During the postoperative period following conventional open surgery, complications included one case of severe respiratory failure, one microembolism of the lower limb, and 2 periprosthetic hematoma. During the follow-up, we observed one pseudo-aneurysm, 3 cases of retrograde ejaculation and one patient with erectile dysfunction after traditional surgery; there was one minor endoleak after endovascular exclusion. CONCLUSIONS: Our experience suggests that ECD is a useful method for arriving at an early diagnosis, while angio-CT imaging is essential for a correct preoperative study. Aneurysms with a diameter equal or greater than 3 cm or that present annual increases in excess of 5 mm represent a correct indication for treatment. Conventional open surgery is the treatment of choice for young patients in good general conditions. Endovascular exclusion is indicated when the patient's clinical conditions contraindicate open surgery and the morphology of the aneurysmal arterial district allows the endoprosthesis to be safely implanted. PMID- 17342035 TI - Usefulness of N-terminal pro-B-type natriuretic peptide levels in predicting residual myocardial ischemia in patients with ST elevation acute myocardial infarction. AB - AIM: N-terminal pro-b-type natriuretic peptide (NT pro-BNP) is a neurohormone synthesized predominantly in ventricular myocardium. In patients with symptoms of heart failure, elevation in NT pro-BNP accurately identifies ventricular dysfunction. However, NT pro-BNP levels are not specific for ventricular dysfunction in patients who do not have overt symptoms of heart failure, suggesting that other cardiac processes such as myocardial ischemia may also cause elevation in NT pro-BNP. The study was aimed to determine whether NT pro BNP elevations are associated with myocardial ischemia. METHODS: One hundred and thirty patients (104 males, 26 females, mean age 61+12 years), with ST elevation acute myocardial infarction (STEMI) and preserved left ventricular ejection fraction (>45%) at echocardiography performed at entry, from February 2003 and February 2004 were enrolled. In all patients NT pro-BNP plasma levels were checked at entry and 4-5 days after symptoms onset. In addition, maximal or symptom-limited exercise treadmill test (Bruce protocol), and myocardial perfusion scintigraphy using [(99m)Tc]Tetrofosmin single photon emission computed tomography (SPECT) imaging were performed within 30 days of STEMI. Ischemia was defined as reversible perfusion abnormalities. RESULTS: Of the 130 participants, 66 (51%) had inducible ischemia. Compared with patients in the lowest tertile, those in the highest tertile of NT pro-BNP had a greater significant risk of residual ischemia (odds ratio: 8.66; 95% CI, 3.90 to 19.24). Nevertheless patients in the highest tertile were older (64.19+/-10.80 years versus 55.90+/ 9.67 years, P = 0.0001), had a lower left ventricular ejection fraction (49.70+13.46% versus 59.49+/-6.58%, P = 0.0001) and had a great rate of acute myocardial infarction (anterior acute myocardial infarction = 40.63% versus 25%). CONCLUSIONS: Elevated levels of NT pro-BNP are associated with residual myocardial ischemia among patients with STEMI and preserved left ventricular ejection fraction, as demonstrated by perfusion defect on SPECT imaging, suggesting that these patients may need further evaluation for stratification of the future risk of fatal events. The observed association between NT pro-BNP levels and ischemia may explain because tests for NT pro-BNP are not specific for ventricular dysfunction among patients with coronary artery disease. PMID- 17342036 TI - Dobutamine stress echocardiography and left ventricular mass changes of mechanical aortic valve replacement in four years follow-up. AB - AIM: The aim of this study was to investigate the differences in cardiac response to stress according to the size of the prosthetic valve in patients who underwent aortic valve replacement (AVR) and to evaluate the relationship between the size of the prosthetic valve and cardiac recovery-remodeling after the operation. METHODS: Thirty patients who had undergone AVR (12 patients) or double valve replacement (18 patients) underwent dobutamine-stress echocardiography 4.2 years after the operation to evaluate response to stress . They were divided into 2 groups according to valve prosthesis size. The small-size AVR group (group 1, n=17) had prosthetic aortic valves 21 pounds mm; the large-size AVR group (group 2, n=13) had valves >21 mm. Response to stress and preoperative and postoperative echocardiographic findings were compared. Pulsed and continuous-wave Doppler studies were performed at rest and at the end of each stage. Peak and mean aortic gradients, left ventricular diastolic and systolic functions were measured for each group. RESULTS: Dobutamine stress increased heart rate and blood pressure in both groups. Peak pressure gradient across the aortic valve prostheses was 42.1 mm Hg in group 1 and 20.9 mm Hg in group 2 (P<0.05) at rest. After dobutamine infusion, the peak pressure gradient across the aortic valve prostheses increased to 85.1 mm Hg in group 1 and 54 mm Hg in group 2 (P<0.05). Isovolumetric relaxation time returned to normal in both groups following dobutamine infusion; this decrease was significant only in group 1. Patients achieved a decrease in left atrium and left ventricular diameters and volumes, as evidence of remodeling following AVR. Left ventricular mass index (LVMI) decreased from 127.6+/-47.6 to 98.1+/-36.9 and from 159.9+/-16.1 to 125.3+/-10.1 in groups 1 and 2, respectively, but this decline was not statistically significant. CONCLUSIONS: Smaller valves have higher gradients and this significant difference increases under stress. Significant improvement in echocardiographic diameters, cardiac filling volumes and LVMI reflects the benefit of the operation. Cardiac remodeling is independent of valve size, although high transprosthetic gradients occur during stress conditions. PMID- 17342037 TI - Symptomatic carotid stenosis. Diagnosis and treatment guidelines. Juridical and medico-legal approach. AB - An increasing body of health care regulations and the growing concern of physicians and patients about health care services have sharpened the debate surrounding the concept of quality in medicine. Once unknown terms such as audit, peer review, accreditation, ISO 9000, quality assurance (QA), continuous quality improvement (CQI) and risk management have become more familiar but also less clear. Following recent reports, medical error has been cited as a result of a health care system that has not yet fully embraced the tenets of quality management. A clearer explanation of definitions, knowledge and procedures is therefore needed. In Italy, the general debate on surgical risk led to a proposal to implement control systems that would monitor the work of each team member in the operating room, from the patient's arrival to transfer to the floor. But to understand the dynamics of doubtful cases, we need to start from new concepts that release the surgeon from the role of ''high priest in the surgery temple.'' Such concepts would underpin a process analysis of how much is effectively done and by whom. This means, on one hand, developing a greater awareness of one's role and competences, and on the other, delineating the stages within which each health care professional is expected to operate. Entering into the debate are the guidelines scientific societies have drawn up to rationalise and improve health care delivery through recommendations directed at optimizing the efficacy and efficiency of surgical intervention as the result of scientific evaluation and clinical observation. However, the critics in question do not always allow the surgeon to work under a medico-legal ''guarantee'' that covers his medical conduct. Further-more, they can be a double-edged sword in court if not adequately considered and critically evaluated with regard to a specific case, the object of censure and charge. In fact, they can be ''exploited'' as an instrument of accusation or defence in an arena where the mass media rush to blame the surgeon but later forget to duly report the acquittal of charges held against the surgeon. The present article examines the light and dark sides of guidelines, taking as an example those profiled by the Italian Society of Vascular and Endovascular Surgery and based on international guidelines for the treatment of symptomatic carotid stenosis. PMID- 17342038 TI - Stent thrombosis in the era of drug eluting stents. AB - Despite a marked reduction in restenosis and the need for repeat revascularization procedures with the use of drug-eluting stents (DES), the risk for stent thrombosis remains of serious concern. Although the safety profiles of DES dose not seem to differ from those of bare metal stent (BMS) in the acute and subacute phases following coronary intervention, recent data suggest a potential increase of thrombotic events late after DES deployment. The main factors associated with late stent thrombosis remain elusive. Delayed re endothelialization, hypersensitivity reaction, technical and mechanical factors and hypercoagulability have all been proposed as contributing factors. It is unlikely that any of these variables alone can cause stent thrombosis, as the incidence of each factor is much higher than the currently known rates of DES thrombosis. Further, temporal appearances of the thrombotic events represent a challenge to our understanding of re-endothelialization, as one would expect that endothelial coverage would be higher in the later phases after treatment. New expanded definitions of stent thrombosis, which also include events secondary to repeat revascularization, have been proposed to provide a better comparative endpoint between BMS and DES. Such clinical attempt to characterize stent thrombosis is valuable, but does not provide much insight into the pathophysiology and intrinsic thrombotic risk of each device. A true progress in this field will only be possible after we improve our understanding of the patho physiology of very late stent thromboses, which may differ from events occurring earlier after treatment. The incidence of stent thrombosis remains rare, but its potential catastrophic consequences should remind clinicians and scientists to make every effort to develop strategies and technologies for its prevention. The topic of stent thrombosis in the era of DES will be reviewed in this article. PMID- 17342039 TI - Perioperative clinical decision-making in surgery for mitral valve repair. AB - Echocardiography has played a critical role in the progress in mitral valve reconstructive surgery which was revolutionized as ''the French correction'' by Alain Carpentier in the mid 1980s. Mitral regurgitation (MR) is the most challenging valvular heart disease throughout the world and is related to rheumatic etiology in the underdeveloped world and to degenerative etiology in the Western world. Echocardiography plays an integral role in the management of patients with significant MR. This includes evaluation and follow-up during the medical management phase of MR to intraoperative mitral valve repair and post operative follow-up, using a combination of transthoracic echocardiography and transesophageal echocardiography. Newer developments include evaluation by transthoracic and transesophageal three-dimensional echocardiography. This review summarizes role of echocardiography in diagnosis, therapy and follow-up of patients with clinically significant MR. Discussion will focus on mitral valve repair for degenerative MR of myxomatous etiology and functional and ischemic MR. PMID- 17342040 TI - Intraoperative transesophageal echocardiography during valve replacement surgery. A review. AB - Intraoperative transesophageal echocardiography (IOTEE) has become an important diagnostic and monitoring tool in the operating theatre during cardiac and noncardiac operations. However, its routine application during valve replacement operations has not received universal recognition. The cumulative experience, brought up in this review, shows that IOTEE is invaluable during valve replacement operations. It has an important role in the consolidation of operative strategy, although it is generally better to obtain all the anatomical and physiological data and the resultant operative strategy in advance, outside the operating room environment. Important data influencing the operative plan has been reported in 3-29% of operations in various studies. The postpump IOTEE is also essential for numerous reasons: it can rule out important misfortunes, such as leaflet immobilization or perivalvular leak, leaky bioprosthesis or coronary obstruction due to valve struts, and is responsible for second pump-run in 3-6% of cases; it is essential in monitoring the deairing process; it provides the surgeon and the anesthesiologist data on biventricular function and volume and exclusion of dynamic left ventricular outflow tract obstruction, and, therefore, guides pharmacotherapy, volume handling and mechanical assistance, including intra-aortic balloon pump indication and location. In conclusion, IOTEE is an essential tool in patients undergoing valve replacement operations, and should be used on a standard basis. PMID- 17342041 TI - The role of echocardiography in mitral valve dysfunction after repair. AB - The echocardiographer responsible for the intraoperative evaluation should be familiar with the transesophageal echocardiography (TEE) views of mitral valve morphology as well as the the repair procedure(s) in order to assess postoperative results. The most frequent immediate mitral valve repair failures are a result of extensive valve disease, calcification, suture dehiscence, ischemia, technical misadventures, stenosis, or systolic anterior motion. Systolic anterior motion with left ventricular outflow tract obstruction and an associated posteriorly directed jet of mitral regurgitation is the most common cause of immediate failure after mitral valve repair. The incidence of this potentially devastating complication has decreased dramatically since the introduction of preoperative measures (sliding annuloplasty and anterior leaflet valvuloplasty) in those patients at risk. Intraoperative TEE is extremely valuable in evaluating the competency of the mitral valve following repair. In fact the results of this modality have a predictive valve in determining long term outcomes in these patients. PMID- 17342042 TI - Echocardiography and cardiac assist devices. AB - Mechanical circulatory support is, nowadays, a well established treatment modality for end stage heart failure. Patients candidate for cardiac transplantation who decompensate while awaiting graft can be supported by long term left ventricular assist devices (long-term LVAD). These devices are intracorporeal pumps, expensive and complicated to install, but offer the advantages of a high cardiac output and a good patient mobility. Echocardiography is usually applied to any kind of LVAD to accomplish: preoperative evaluation to exclude contraindications, intraoperative when circulatory support starts to assess left ventricular (LV) filling and unloading, postoperative evaluation during intensive care unit course to prevent hypovolemia, cardiac tamponade and right ventricular failure, controls during assistance for suspected device malfunction. Short-term devices are utilized as acute support after the initial resuscitation of the patient. These devices are bedside extracorporeal pumps, less expensive and less complicated to install. They provide a brief but sufficient time to wait patient recovery (''bridge to recovery'') or to evaluate further therapies (''bridge to long-term device'' or ''bridge to transplantation''). Echocardiography has an important role during implantation to guide cannulae positioning, to prevent insufficient LV unloading, to detect echo contrast enhancement with blood stagnation and intracardiac clot formation, to titrate pharmacologic support, and to assess myocardial recovery. PMID- 17342043 TI - Role of echocardiography in aortic atherosclerotic disease and stroke. AB - Patients with severe aortic atherosclerosis are at high risk for stroke. The risk is highest for those with atherosclerotic plaque measuring = or >4 mm in thickness. There is currently no proven medical therapy to reduce embolic risk in patients with aortic plaque. Antiplatelet therapy, smoking cessation, and management of diabetes and hypertension are important. Retrospective data support the use of statins to prevent stroke in patients with severe aortic plaque. Embolism from aortic atherosclerosis may occur spontaneously, or less commonly, as a complication of invasive or surgical cardiovascular procedures. Transesophageal echocardiography (TEE) is the procedure of choice for the characterization of plaque and the detection of superimposed mobile thrombi. Therefore, TEE is a useful tool to identify patients at high risk for stroke. For patients who are being evaluated for coronary artery bypass graft (CABG) surgery or coronary angiography, the risks and benefits of these procedures must be carefully weighed and alternate approaches should be considered in patients with severe plaque. Options include off-pump CABG or coronary angiography via a brachial (rather than femoral) approach. PMID- 17342044 TI - Tissue Doppler analysis: does the false negative exist? PMID- 17342045 TI - Ultrastructural and nervous characteristics of the aortic valve: surgical implications. PMID- 17342046 TI - Collecting large cohorts of patients with uncommon diseases: mission impossible? PMID- 17342047 TI - Comparison of bacterial composition between human saliva and dental unit water system. AB - The bacterial compositions between the dental unit water system and human saliva were characterized and compared by direct sequence analysis of 16S rDNA clone libraries. Based on the species richness estimation, bacterial diversity in the dental unit water system (DUW) was more diverse than that of the human saliva (HS). The Chao1 estimates of species richness in HS and DUW samples were 12.0 and 72.4, respectively. The total numbers of OTUs observed in the combined libraries accounted for 83% (HS) and 59% (DUW) of the Chao1 diversity estimate as defined at the 80% similarity threshold. Based on the sequence analysis, the phylum Proteobacteria was the major group in both clone libraries at phylum level. DUW clone library contained 80.0% Proteobacteria, 8.0% Bacteroides, 4.0% Nitrospira, 4.0% Firmicutes, 2.0% Planctomycetes and 2.0% Acidobacteria. On the other hand, human saliva (HS) clone library contained 55.5% Proteobacteria, 36.1% Firmicutes and 8.4% Bacteroides. The majority of bacteria identified belonged to phylum Proteobacteria in both samples. In dental unit water system (DUW), Alphaproteobacteria was detected as the major group. There was no evidence of the bacterial contamination due to a dental treatment. Most sequences were related to microorganisms derived from biofilm in oligotrophic environments. PMID- 17342048 TI - Production and biological activity of laidlomycin, anti-MRSA/VRE antibiotic from Streptomyces sp. CS684. AB - Culture broth of a streptomycete isolate, Streptomyces sp. CS684 showed antibacterial activity on methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE). Among purified substances from the organism, CSU-1, which is active against MRSA and VRE, is a C37H62O12Na (M+, 721.3875), and identified as laidlomycin. The anti-MRSA and anti-VRE activity of CSU-1 was stronger than oxacillin and vancomycin. Phylogenetic analysis showed that strain CS684 is very similar to Streptomyces ardus NRRL 2817T, whereas the ability of Streptomyces sp. CS684 to produce laidlomycin was shown to be unique. PMID- 17342049 TI - Evaluation of endophytic colonization of Citrus sinensis and Catharanthus roseus seedlings by endophytic bacteria. AB - Over the last few years, the endophytic bacterial community associated with citrus has been studied as an important component interacting with Xylella fastidiosa, the causal agent of citrus variegated chlorosis (CVC). This bacterium may also colonize some model plants, such as Catharanthus roseus and Nicotiana clevelandii. In the present study, we compared the endophytic colonization of Citrus sinensis and Catharanthus roseus using the endophytic bacteria Klebsiella pneumoniae. We chose an appropriate strain, K. pneumoniae 342 (Kp342), labeled with the GFP gene. This strain was inoculated onto seedlings of C. sinensis and C. roseus. The isolation frequency was determined one week after the inoculation and the endophytic colonization of K. pneumoniae was observed using fluorescence microscopy. Although the endophytic bacterium was more frequently isolated from C. roseus than from C. sinensis, the colonization profiles for both host plants were similar, suggesting that C. roseus could be used as a model plant to study the interaction between endophytic bacteria and X. fastidiosa. PMID- 17342050 TI - Differential response of etiolated pea seedlings to inoculation with rhizobacteria capable of utilizing 1-aminocyclopropane-1-carboxylate or L methionine. AB - The majority of soil microorganisms can derive ethylene from L-methionine (L MET), while some rhizobacteria can hydrolyze 1-aminocyclopropane-1-carboxylate (ACC) due to their ACC-deaminase activity. In this study, three strains having either ACC-deaminase activity (Pseudomonas putida biotype A, A7), or the ability to produce ethylene from L-MET (Acinetobacter calcoaceticus, M9) or both (Pseudomonas fluorescens, AM3) were used for inoculation. The highly ethylene specific bioassay of a classical "triple" response in pea seedlings was used to investigate the effect of the inoculation with the rhizobacteria in the presence of 10 mM ACC or L-MET. The exogenous application of ACC had a concentration dependent effect on the etiolated pea seedlings in creating the classical "triple" response. The inoculation with P. putida diluted the effect of ACC, which was most likely due to its ACC-deaminase activity. Similarly, the application of Co2+ reduced the ACC-imposed effect on etiolated pea seedlings. In contrast, the inoculation of A. calcoaceticus or P. fluorescens in the presence of L-MET caused a stronger classical "triple" response in etiolated pea seedlings; most likely by producing ethylene from L-MET. This is the first study, to our knowledge, reporting on the comparative effect of rhizobacteria capable of utilizing ACC vs L-MET on etiolated pea seedlings. PMID- 17342051 TI - Comparative genomics profiling of clinical isolates of Helicobacter pylori in Chinese populations using DNA microarray. AB - In order to search for specific genotypes related to this unique phenotype, we used whole genomic DNA microarray to characterize the genomic diversity of Helicobacter pylori (H. pylori) strains isolated from clinical patients in China. The open reading frame (ORF) fragments on our microarray were generated by PCR using gene-specific primers. Genomic DNA of H. pylori 26695 and J99 were used as templates. Thirty-four H. pylori isolates were obtained from patients in Shanghai. Results were judged based on ln(x) transformed and normalized Cy3/Cy5 ratios. Our microarray included 1882 DNA fragments corresponding to 1636 ORFs of both sequenced H. pylori strains. Cluster analysis, revealed two diverse regions in the H. pylori genome that were not present in other isolates. Among the 1636 genes, 1091 (66.7%) were common to all H. pylori strains, representing the functional core of the genome. Most of the genes found in the H. pylori functional core were responsible for metabolism, cellular processes, transcription and biosynthesis of amino acids, functions that are essential to H. pylori's growth and colonization in its host. In contrast, 522 (31.9%) genes were strain-specific genes that were missing from at least one strain of H. pylori. Strain-specific genes primarily included restriction modification system components, transposase genes, hypothetical proteins and outer membrane proteins. These strain-specific genes may aid the bacteria under specific circumstances during their long-term infection in genetically diverse hosts. Our results suggest 34 H. pylori clinical strains have extensive genomic diversity. Core genes and strain-specific genes both play essential roles in H. pylori propagation and pathogenesis. Our microarray experiment may help select relatively significant genes for further research on the pathogenicity of H. pylori and development of a vaccine for H. pylori. PMID- 17342052 TI - Identification of genes differentially expressed in RAW264.7 cells infected by Salmonella typhimurium using PCR method. AB - Salmonella typhimurium, causing mouse typhoid, infects hosts such as macrophage cells, and proliferates in intracellular vacuoles causing infected cells to trigger numerous genes to respond against the infection. In this study, we tried to identify such genes in RAW264.7 cells by using the PCR screening method with degenerate primers. Fourteen genes were found to be differentially expressed after a 4 h infection in which the expression of 8 genes increased while expression of the others decreased. Most of the genes were involved in proinflammatory responses such as cytokines production and cell death. The mutation in msbB gene encoding the myristoyl transferase in lipid A of lipopolysaccharide (LPS) resulted in much lower toxicity to the inoculated animals. We compared the expression of the identified genes in wild-type and msbB mutated S. typhimurium infections and found that Lyzs encoding lysozyme type M was differentially expressed. This gene is quite likely to be related to bacterial survival in the host cells. PMID- 17342053 TI - Requirement of Bni5 phosphorylation for bud morphogenesis in Saccharomyces cerevisiae. AB - In budding yeast, G2/M transition is tightly correlated with bud morphogenesis regulated by Swe1 and septin that plays as a scaffold to recruits protein components. BNI5 isolated as a suppressor for septin defect is implicated in septin organization and cytokinesis. The mechanism by which Bni5 regulates normal septin function is not completely understood. Here, we show that Bni5 phosphorylation is required for mitotic entry regulated by Swe1 pathway. Bni5 modification was evident from late mitosis to G1 phase, and CIP treatment in vitro of affinity-purified Bni5 removed the modification, indicative of phosphorylation on Bni5. The phosphorylation-deficient mutant of BNI5 (bni5-4A) was defective in both growth at semi-restrictive temperature and suppression of septin defect. Loss of Bni5 phosphorylation resulted in abnormal bud morphology and cell cycle delay at G2 phase, as evidenced by the formation of elongated cells with multinuclei. However, deletion of Swe1 completely eliminated the elongated-bud phenotypes of both bni5 deletion and bni5-4A mutants. These results suggest that the bud morphogenesis and mitotic entry are positively regulated by phosphorylation-dependent function of Bni5 which is under the control of Swe1 morphogenesis pathway. PMID- 17342054 TI - Defining the N-linked glycosylation site of Hantaan virus envelope glycoproteins essential for cell fusion. AB - The Hantaan virus (HTNV) is an enveloped virus that is capable of inducing low pH dependent cell fusion. We molecularly cloned the viral glycoprotein (GP) and nucleocapsid (NP) cDNA of HTNV and expressed them in Vero E6 cells under the control of a CMV promoter. The viral gene expression was assessed using an indirect immunofluorescence assay and immunoprecipitation. The transfected Vero E6 cells expressing GPs, but not those expressing NP, fused and formed a syncytium following exposure to a low pH. Monoclonal antibodies (MAbs) against envelope GPs inhibited cell fusion, whereas MAbs against NP did not. We also investigated the N-linked glycosylation of HTNV GPs and its role in cell fusion. The envelope GPs of HTNV are modified by N-linked glycosylation at five sites: four sites on G1 (N134, N235, N347, and N399) and one site on G2 (N928). Site directed mutagenesis was used to construct eight GP gene mutants, including five single N-glycosylation site mutants and three double-site mutants, which were then expressed in Vero E6 cells. The oligosaccharide chain on residue N928 of G2 was found to be crucial for cell fusion after exposure to a low pH. These results suggest that G2 is likely to be the fusion protein of HTNV. PMID- 17342055 TI - Development of a virus concentration method and its application for the detection of noroviruses in drinking water in China. AB - A new procedure for the concentration of nonoviruses from water samples has been developed. This procedure (calcium flocculation-citrate dissolution method) uses the following steps: virus flocculation formed by treatment with 1 M CaCl2 and 1 M Na2HPO4, virus release by sodium citrate dissolution (0.3 M Na citrate, pH 3.5), and virus re-concentration by ultrafiltration. When reverse transcription (RT)-PCR was performed after the procedure, the overall detection sensitivity for seeded noroviruses in a one liter drinking water sample was as low as 1 RT-PCR unit, which is equal to a 10-6 dilution of the virus sample. This approach showed at least a 5-fold-higher sensitivity than the current method with its three steps of adsorption-elution-concentration. The newly developed procedure was used to test different brands of bottled drinking water from China for putative contamination with noroviruses. A total of 144 samples were analyzed; all of the samples were negative for norovirus specific nucleic acids. PMID- 17342056 TI - The antimicrobial activity of essential oil from Dracocephalum foetidum against pathogenic microorganisms. AB - A number of essential oils from Mongolian aromatic plants are claimed to have antimicrobial activities. The essential oil of Dracocephalum foetidum, a popular essential oil used in Mongolian traditional medicine, was examined for its antimicrobial activity. Eight human pathogenic microorganisms including B. subtilis, S. aureus, M. lutens, E. hirae, S. mutans, E. coli, C. albicans, and S. cerevisiae were examined. The essential oil of Dracocephalum foetidum exhibited strong antimicrobial activity against most of the pathogenic bacteria and yeast strains that were tested; by both the agar diffusion method and the minimum inhibitory concentration (MIC) assay (MIC range was 26-2592 microg/ml). Interestingly, Dracocephalum foetidum even showed antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. We also analyzed the chemical composition of the oil by GC-MS and identified several major components, including n-Mentha-1,8-dien-10-al, limonene, geranial, and neral. PMID- 17342057 TI - Studies on synonymous codon and amino acid usage biases in the broad-host range bacteriophage KVP40. AB - In this study, the relative synonymous codon and amino acid usage biases of the broad-host range phage, KVP40, were investigated in an attempt to understand the structure and function of its proteins/protein-coding genes, as well as the role of its tRNAs. Synonymous codons in KVP40 were determined to be ATrich at the third codon positions, and their variations are dictated principally by both mutational bias and translational selection. Further analysis revealed that the RSCU of KVP40 is distinct from that of its Vibrio hosts, V. cholerae and V. parahaemolyticus. Interestingly, the expression of the putative highly expressed genes of KVP40 appear to be preferentially influenced by the abundant host tRNA species, whereas the tRNAs expressed by KVP40 may be required for the efficient synthesis of all its proteins in a diverse array of hosts. The data generated in this study also revealed that KVP40 proteins are rich in low molecular weight amino acid residues, and that these variations are influenced primarily by hydropathy, mean molecular weight, aromaticity, and cysteine content. PMID- 17342058 TI - The diversity of multi-drug resistance profiles in tetracycline-resistant Vibrio species isolated from coastal sediments and seawater. AB - In this study we examined the multi-drug resistance profiles of the tetracycline (TC) resistant genus Vibrio to determine its susceptibility to two beta-lactams, ampicillin (ABPC), and mecillinam (MPC), as well as to macrolide, erythromycin (EM). The results showed various patterns of resistance among strains that were isolated from very close geographical areas during the same year, suggesting diverse patterns of drug resistance in environmental bacteria from this area. In addition, the cross-resistance patterns suggested that the resistance determinants among Vibrio spp. are acquired differently within the sediment and seawater environments. PMID- 17342059 TI - Genetic characterization of the Escherichia coli O66 antigen and functional identification of its wzy gene. AB - Escherichia coli is a clonal species, and occurs as both commensal and pathogenic strains, which are normally classified on the basis of their O, H, and K antigens. The O-antigen (O-specific polysaccharide), which consists of a series of oligosaccharide (O-unit) repeats, contributes major antigenic variability to the cell surface. The O-antigen gene cluster of E. coli O66 was sequenced in this study. The genes putatively responsible for the biosynthesis of dTDP-6-deoxy-L talose and GDP-mannose, as well as those responsible for the transfer of sugars and for O-unit processing were identified based on their homology. The function of the wzy gene was confirmed by the results of a mutation test. Genes specific for E. coli O66 were identified via PCR screening against representatives of 186 E. coli and Shigella O type strains. The comparison of intergenic sequences located between galF and the O-antigen gene cluster in a range of E. coli and Shigella showed that this region may perform an important function in the homologous recombination of the O-antigen gene clusters. PMID- 17342060 TI - Analysis of substitution events in HIV-1 vif gene of the Korean clade. AB - Nucleotide and amino acid substitution pattern in vif gene of the Korean clade of HIV-1 isolated from Koreans were analyzed using consensus sequences. At nucleotide level, transition/transversion substitution ratio was 1.88, and nonsynonymous/synonymous substitution ratio was 2.67, suggesting a divergent evolution in the Korean clade. At amino acid level, there were 17 substitutions and G-->E substitution at position 37 may be responsible for change in predicted secondary structure. PMID- 17342061 TI - Nucleotide sequence and secondary structure of 5S rRNA from Sphingobium chungbukense DJ77. AB - The 5S rRNA gene from Sphingobium chungbukense DJ77 was identified. The secondary structure of the 199-base-long RNA was proposed. The two-base-long D loop was the shortest among all of the known 5S rRNAs. The U19-U64 non-canonical pair in the helix II region was uniquely found in strain DJ77 among all of the sphingomonads. PMID- 17342062 TI - Carotid stenting versus endarterectomy: the controversy continues. PMID- 17342063 TI - Intensive insulin therapy for the critically ill hospitalized patient-do the benefits outweigh the risks? PMID- 17342064 TI - Comprehensive analysis of MHC-II expression in healthy human skin. AB - A number of antigen-presenting cells (APCs) expressing major histocompatibility complex class II (MHC-II) have been identified in healthy human skin including the Langerhans cells of the epidermis and the three recently defined dermal APC subsets. It is well documented that in other tissues HLA-DR expression is not exclusive to APCs. Following a comprehensive analysis of the cells in human skin using flow cytometry and fluorescence immunohistochemistry, we have identified additional cell subsets that express HLA-DR. Using markers exclusive for blood and lymphatic endothelium, we demonstrated that both of these cell populations have the capacity to express HLA-DR. In addition, a small subset of dermal T lymphocytes was found to express low-level HLA-DR suggesting an activated phenotype. Dermal T lymphocytes were often in intimate contact with either CD1a(+) CD207(-) dermal APCs or CD1a(+) CD207(+) dermal Langerhans cells, possibly explaining the activated phenotype of a subset of dermal T lymphocytes. PMID- 17342065 TI - Is EUS-guided FNA biopsy the best diagnostic tool for lymphadenopathy of unknown origin? PMID- 17342066 TI - Asymptomatic urinary tract infection is unlikely to cause proteinuria or microalbuminuria. PMID- 17342067 TI - Does a vascular access surveillance program reduce access-related costs and complications? PMID- 17342068 TI - Oral rizatriptan--an effective migraine therapy in pediatric patients? PMID- 17342069 TI - Antithrombotic treatment and stroke severity in patients with atrial fibrillation. PMID- 17342070 TI - Cardiac side effects of trastuzumab: lessons learned from targeting cancer pathways. PMID- 17342071 TI - Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects. AB - BACKGROUND: Abdominal obesity and hypertriglyceridemia (the hypertriglyceridemic waist phenotype) increase cardiovascular risk. The very low-density lipoprotein (VLDL) is a triglyceride (TG)-rich particle. Frequent variations in the genes coding for enzymes and proteins involved in the VLDL catabolism have already been documented. The epistatic effect of such variants on the risk profile associated with abdominal obesity remains to be elucidated. OBJECTIVE: This study aims to assess the effect of combinations of frequent single-nucleotide polymorphisms (SNPs) in the VLDL catabolic pathway on the relation between abdominal obesity and fasting TG. METHOD: Only gene variants in the lipoprotein lipase, apolipoprotein (apo) CIII, hepatic lipase and apo E genes known to be frequent in the general population (allele frequency>5%) were included in this study. The presence of selected SNPs was detected by polymerase chain reaction-restriction fragment length polymorphism in a sample of 640 non-diabetic French Canadians at high cardiovascular risk (405 obese, 235 non-obese). RESULTS: Carrying more than two frequent gene variants involved in the VLDL catabolic pathway significantly increased the risk of hyperTG (odds ratio of TG>1.7 mmol/l=4.15; P=0.001). This effect was proportional to the number of SNPs and genes involved and was significantly amplified by the presence of abdominal obesity defined on the basis of waist circumference. CONCLUSION: When combined with abdominal obesity, epistasis in the VLDL pathway has a deleterious effect on fasting TG and coronary artery disease risk profile according to the TG threshold (1.7 mmol/l) used in medical guidelines for the assessment of the metabolic syndrome and associated risk. PMID- 17342072 TI - Association analysis of vitamin D-binding protein gene polymorphisms with variations of obesity-related traits in Caucasian nuclear families. AB - BACKGROUND: Vitamin D-binding protein (DBP) gene is well known for its function on glucose and vitamin D metabolism in human populations. Previous studies suggested that the in vivo DBP level may play a role in the etiology of obesity. However, few studies explored the contribution of DBP gene to the variance of obesity phenotypes. OBJECTIVE: To investigate the relationship of DBP polymorphisms and obesity in Caucasian nuclear families. DESIGN: We genotyped 14 single-nucleotide polymorphisms (SNPs) located in and around the DBP gene in 1873 Caucasian subjects from 405 nuclear families. Three obesity-related quantitative phenotypes were investigated, including body mass index (BMI), fat mass and percentage of fat mass (PFM). Single SNPs and haplotypes (three blocks) were tested by family-based association using the FBAT software. RESULTS: SNP2 (rs17467825) and its corresponding haplotype GAA (frequency 0.270) in block 1 showed strongest associations with PFM (P=0.0011 and 0.0023, respectively). In multivariate test significant association was also observed for SNP2 with fat mass&BMI&PFM (P=0.0098). Subsequent sex-stratified analyses demonstrated nominal association for SNP2 and haplotype GAA with PFM in the female subgroup. CONCLUSION: Polymorphisms of DBP gene were significantly association with human PFM, especially in female, suggesting the importance of DBP gene in the pathogenesis of human obesity. PMID- 17342073 TI - Fast food: friendly? AB - Fast food is routinely blamed for the obesity epidemic and consequentially excluded from professional dietary recommendations. However, several sections of society including senior citizens, low-income adult and children, minority and homeless children, or those pressed for time appear to rely on fast food as an important source of meals. Considering the dependence of these nutritionally vulnerable population groups on fast food, we examined the possibility of imaginative selection of fast food, which would attenuate the potentially unfavorable nutrient composition. We present a sample menu to demonstrate that it is possible to design a fast food menu that provides reasonable level of essential nutrients without exceeding the caloric recommendations. We would like to alert health-care professionals that fast food need not be forbidden under all circumstances, and that a fresh look at the role of fast food may enable its inclusion in meal planning for those who depend on it out of necessity, while adding flexibility. PMID- 17342074 TI - Habitual physical activity differentially affects acute and short-term energy intake regulation in young and older adults. AB - BACKGROUND: Energy intake (EI) regulation is impaired in older adults, but it is not known if habitual physical activity affects accuracy of EI regulation in older compared with young adults. OBJECTIVE: We hypothesized that the ability to compensate for a high-energy yogurt preload beverage at a subsequent ad libitum meal (i.e. acute compensation) and over the course of the testing day (i.e. short term compensation) would decrease with age, but the magnitude of the decline would be smaller in physically active compared with sedentary older adults. DESIGN: On two occasions, young active (n=15), young sedentary (n=14), older active (n=14) and older sedentary (n=11) subjects consumed either a high-energy yogurt preload beverage (YP: 500 ml, 1988 kJ, men; 375 ml, 1507 kJ, women), or no preload (NP), 30 min before an ad libitum test meal. EI at both ad libitum meals was measured, and total daily EI was determined on both testing days. Percent EI compensation for the YP was calculated for the test meal and testing day to determine acute and short-term compensation. RESULTS: Percent EI compensation at the test meal was significantly lower in the older compared with the young subjects (65+/-4 vs 81+/-4%, P=0.005). There was no effect of habitual physical activity level on acute compensation, and no age by physical activity level interaction (P=0.60). In contrast, short-term compensation was not different with age (87+/-5 vs 93+/-6%, older vs young, P=0.45), but was more accurate in active vs sedentary subjects (100+/-5 vs 79+/-6%, P=0.01). As with acute compensation, there was no age by physical activity interaction (P=0.39). CONCLUSION: Acute EI regulation is impaired in older adults, which is not attenuated by physical activity status. However, EI regulation over the course of a day is more accurate in active vs sedentary adults, which may facilitate long-term energy balance. Future work is needed to determine if higher energy expenditure in older active vs older sedentary adults improves long-term EI regulation. PMID- 17342075 TI - BMI, fat and muscle differences in urban women of five ethnicities from two countries. AB - OBJECTIVE: To investigate body composition differences, especially the relationship between body mass index (BMI) and percent body fat (%BF), among five ethnic groups. DESIGN: Cross-sectional. SUBJECTS: Seven hundred and twenty-one apparently healthy women aged 18-60 years (BMI: 17.4-54.0 kg/m(2)) from South Africa (SA, 201 black, 94 European) and New Zealand (NZ, 173 European, 76 Maori, 84 Pacific, 93 Asian Indian). MEASUREMENTS: Anthropometry, including waist circumference, and total, central and peripheral body fat, bone mineral content and total appendicular skeletal muscle mass (ASMM) derived from dual X-ray absorptiometry. RESULTS: Regression analysis determined that at a BMI of 30 kg/m(2), SA European women had a %BF of 39%, which corresponded to a BMI of 29 for SA black women. For a BMI of 30 kg/m(2) in NZ Europeans, equivalent to 43% body fat, the corresponding BMIs for NZ Maori, Pacific and Asian Indian women were 34, 36 and 26 kg/m(2), respectively. Central fat mass was lower in black SA than in European SA women (P<0.001). In NZ, Pacific women had the lowest central fat mass and highest ASMM, whereas Asian Indian women had the highest central fat mass, but lowest ASMM and bone mineral content. CONCLUSIONS: The relationship between %BF and BMI varies with ethnicity and may be due, in part, to differences in central fatness and muscularity. Use of universal BMI or waist cut-points may not be appropriate for comparison of obesity prevalence among differing ethnic groups, as they do not provide a consistent reflection of adiposity and fat distribution across ethnic groups. PMID- 17342076 TI - Heritability of somatotype components: a multivariate analysis. AB - OBJECTIVE: To study the genetic and environmental determination of variation in Heath-Carter somatotype (ST) components (endomorphy, mesomorphy and ectomorphy). DESIGN: Multivariate path analysis on twin data. SUBJECTS: Eight hundred and three members of 424 adult Flemish twin pairs (18-34 years of age). RESULTS: The results indicate the significance of sex differences and the significance of the covariation between the three ST components. After age-regression, variation of the population in ST components and their covariation is explained by additive genetic sources of variance (A), shared (familial) environment (C) and unique environment (E). In men, additive genetic sources of variance explain 28.0% (CI 8.7-50.8%), 86.3% (71.6-90.2%) and 66.5% (37.4-85.1%) for endomorphy, mesomorphy and ectomorphy, respectively. For women, corresponding values are 32.3% (8.9 55.6%), 82.0% (67.7-87.7%) and 70.1% (48.9-81.8%). For all components in men and women, more than 70% of the total variation was explained by sources of variance shared between the three components, emphasising the importance of analysing the ST in a multivariate way. CONCLUSIONS: The findings suggest that the high heritabilities for mesomorphy and ectomorphy reported in earlier twin studies in adolescence are maintained in adulthood. For endomorphy, which represents a relative measure of subcutaneous adipose tissue, however, the results suggest heritability may be considerably lower than most values reported in earlier studies on adolescent twins. The heritability is also lower than values reported for, for example, body mass index (BMI), which next to the weight of organs and adipose tissue also includes muscle and bone tissue. Considering the differences in heritability between musculoskeletal robustness (mesomorphy) and subcutaneous adipose tissue (endomorphy) it may be questioned whether studying the genetics of BMI will eventually lead to a better understanding of the genetics of fatness, obesity and overweight. PMID- 17342077 TI - Body mass index and mortality in men: evaluating the shape of the association. AB - OBJECTIVE: Controversy regarding the relationship between body mass index (BMI) and mortality continues to exist. Most of the previous studies have not comprehensively accounted for major sources of bias. We examined the association between BMI and all-cause mortality according to pre-existing disease and smoking status in a large prospective cohort. METHODS: Participants were 99 253 male physicians in the Physicians' Health Study enrollment cohort (40-84 years) who provided self-reported information in 1982. We used Cox proportional hazards regression to examine the association between baseline BMI and mortality. RESULTS: A total of 5438 men died (median follow-up, 5.7 years). Although a U shaped association between BMI and all-cause mortality was seen among all men, we found a linear relationship when accounting for potential sources of bias. In the optimal model excluding men who died within 2 years, and adjusting for age, smoking, alcohol consumption, physical activity, prior disease and interactions between BMI and prior disease, and between BMI and smoking, those with BMI <20.0 kg/m(2) had a relative risk (RR) of death of 0.88 (95% confidence interval (CI), 0.56-1.40), as compared to men with BMI 22.5-24.9 kg/m(2). By contrast, men with BMI 30.0-34.9 kg/m(2) had an RR of 1.45 (95% CI, 1.10-1.91) and those with BMI >or=35.0 kg/m(2) had an RR of 1.62 (95% CI, 1.12-2.35; P for linear trend, <0.001). According to WHO categories, men in the 'overweight' range (BMI 25.0 29.9 kg/m(2)) had an RR of 1.20 (95% CI, 1.05-1.38) as compared to men in the 'normal' range (BMI <25.0 kg/m(2)). CONCLUSIONS: In this large, prospective cohort, we found a consistent linear association between higher BMI and increased risk of mortality after accounting for several potential sources of bias, even among those within the 'overweight' range of BMI. Public health messages should emphasize the preponderance of evidence supporting the adverse health effects associated with higher body weight. PMID- 17342078 TI - Plasma leptin levels are related to body composition, sex, insulin levels and the A55V polymorphism of the UCP2 gene. AB - OBJECTIVE: Circulating leptin levels show a high degree of individual variability even after the main effect of body fatness is accounted for. We therefore wanted to determine the roles of variation in body composition, age, sex and polymorphisms of the UCP2 gene and promoter region on levels of circulating leptin. SUBJECTS: One hundred and fifty Caucasian subjects, which represented a cross-section of the population from NE, Scotland, were recruited. MEASUREMENTS: Body composition was measured using dual X-ray absorptiometry. Fasted circulating leptin, insulin, T3 and T4 levels were measured, and all individuals were genotyped for the UCP2 polymorphisms A55V, -866G>A and exon-8 ins/del. RESULTS: The results indicate that circulating leptin was significantly related to sex and principle component (PC) scores representing overall adipose tissue mass and a second representing the contrast of central to peripheral bone mineral content. Residual leptin was associated with the A55V polymorphism (P< 0.001) explaining 11.3% of the residual variance. There was a marginal effect associated with exon 8 ins/del (P=0.045) explaining 4.4% of the residual variance in leptin. Log(e) transformed circulating fasting insulin was related to PC scores representing general adiposity and sex. Residual Log(e) insulin was associated with the A55V and exon-8 ins/del polymorphisms explaining 5.7% (P=0.015) and 5% (P=0.026) of the residual variation, respectively. The -866G>A polymorphism was not significantly associated with residual leptin or insulin. Leptin and insulin were significantly (P=0.007) correlated. Statistically removing the effect of insulin on leptin still showed association between leptin and A55V (P=0.002). Removing the effect of leptin on insulin, the A55V polymorphism was no longer significant (P=0.120). After accounting for the correlation between insulin and leptin, the exon-8 ins/del was no longer significant for residual leptin (P=0.119) or Log(e) insulin (P=0.252). CONCLUSION: These data suggest that the A55V polymorphism directly affected the levels of leptin but not via an effect on insulin. PMID- 17342079 TI - NSAIDs and the risk of acute myocardial infarction. PMID- 17342080 TI - Does calcium supplementation increase bone mineral density in healthy children? PMID- 17342081 TI - Can treatment with risedronate benefit patients with knee osteoarthritis? PMID- 17342083 TI - Calcium, dairy, and prostate cancer. PMID- 17342084 TI - MCM immunocytochemistry as a first line cervical screening test in developing countries: a prospective cohort study in a regional cancer centre in India. AB - Cervical screening is not available for the majority of women in resource-poor countries. An important factor is a lack of skilled operators necessary for high throughput assessment of the Papanicolaou (Pap) test currently in use. We compared the efficacy of immunocytochemistry for minichromosome maintenance (MCM) proteins vs standard Pap testing at detecting disease in 455 cervical smears processed in a typical Indian screening laboratory. Conventional (non-monolayer) smears were stained manually and then examined by a cytotechnologist and a cytopathologist. The MCM test was called positive when immunolabelled cells were identified as dyskaryotic by the Pap counterstain. The MCM test was read more quickly than the Pap test (approximately 2 vs 10 min) and there was 100% inter observer agreement compared with 85% for Pap (P<0.0001). The MCM test detected 10 biopsy-proven cancers or pre-cancers that were not detected by Pap (P=0.002; P=0.016 excluding three cases where the Pap was deemed unsatisfactory on review). The cases in question included one recurrent squamous carcinoma and one adenocarcinoma in a screening patient who would have returned to 5 year recall. There were no false positive MCM test results. We propose that MCM immunocytochemistry has considerable advantages for cervical screening in developing countries like India. PMID- 17342085 TI - Interpretation of microarray data in cancer. AB - Microarray studies aim at identifying homogeneous subtypes of cancer patients, searching for differentially expressed genes in tumours with different characteristics, or predicting the prognosis of patients. Using breast cancer as an example, we discuss the hypotheses underlying these studies, their power, and the validity and the clinical usefulness of the findings. PMID- 17342086 TI - Survival following relapse in childhood haematological malignancies diagnosed in 1974-2003 in Yorkshire, UK. AB - We examined population-based information on relapsed childhood haematological cancers, investigating factors that might influence both overall survival and survival following relapse among the 1177 children (0-14 years) diagnosed with a haematological malignancy in Yorkshire from 1974 to 2003, of whom 342 (29%) relapsed at least once. Leukaemia patients from more deprived areas were significantly less likely to relapse (odds ratio=0.54, 95% confidence interval 0.32-0.93 for most deprived quintile vs least deprived quintile; P(trend)=0.06), especially those with acute myeloid leukaemia (P=0.04). Neither ethnic group nor distance to the main treatment centre was associated with risk of relapse. Overall, patients who relapsed at least once had 5-year survival rates of 46% (41 51%) compared with 79% (76-81%) of those who did not. Five-year survival rates from the time of first relapse increased from 20% in 1974-1983 to 45% in 1984 2003. Length of first remission was a strong predictor of survival for leukaemia with a 46% reduced risk of death for every additional year of event-free survival. Of children who experienced a relapse, 46% survived at least 5 years, whereas just under half of patients survived 5 years beyond disease recurrence. This provides a baseline for future comparisons and demonstrates that relapsed childhood cancer need not imply a poor outcome. PMID- 17342087 TI - Study of matrix metalloproteinases and their inhibitors in breast cancer. AB - An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases. PMID- 17342088 TI - Multiple mechanisms underlie defective recognition of melanoma cells cultured in three-dimensional architectures by antigen-specific cytotoxic T lymphocytes. AB - Cancer cells' growth in three-dimensional (3D) architectures promotes resistance to drugs, cytokines, or irradiation. We investigated effects of 3D culture as compared to monolayers (2D) on melanoma cells' recognition by tumour-associated antigen (TAA)-specific HLA-A(*)0201-restricted cytotoxic T-lymphocytes (CTL). Culture of HBL, D10 (both HLA-A(*)0201+, TAA+) and NA8 (HLA-A(*)0201+, TAA-) melanoma cells on polyHEMA-coated plates, resulted in generation of 3D multicellular tumour spheroids (MCTS). Interferon-gamma (IFN-gamma) production by HLA-A(*)0201-restricted Melan-A/MART-1(27-35) or gp 100(280-288)-specific CTL clones served as immunorecognition marker. Co-culture with melanoma MCTS, resulted in defective TAA recognition by CTL as compared to 2D as witnessed by decreased IFN-gamma production and decreased Fas Ligand, perforin and granzyme B gene expression. A multiplicity of mechanisms were potentially involved. First, MCTS per se limit CTL capacity of recognising HLA class I restricted antigens by reducing exposed cell surfaces. Second, expression of melanoma differentiation antigens is downregulated in MCTS. Third, expression of HLA class I molecules can be downregulated in melanoma MCTS, possibly due to decreased interferon regulating factor-1 gene expression. Fourth, lactic acid production is increased in MCTS, as compared to 2D. These data suggest that melanoma cells growing in 3D, even in the absence of immune selection, feature characteristics capable of dramatically inhibiting TAA recognition by specific CTL. PMID- 17342089 TI - Apoptosis assays with lymphoma cell lines: problems and pitfalls. AB - Much attention has been focused on the manner in which tumour cells die after treatment with cytotoxic agents. The basic question is whether cells die via apoptosis or via direct damage from the toxic agent. Various assays have been used to make this distinction. However, we show herein that some of the widely used assays for apoptosis do not in fact distinguish between apoptosis and other forms of cell death. More specifically: (1) A sub-G1 DNA content, identified by propidium iodide staining, does not distinguish between apoptotic and necrotic cells; (2) loss of mitochondrial membrane potential does not distinguish between apoptotic and necrotic cells, unless combined with an assay for an intact cell membrane; (3) subcellular fragments that arise from dead cells or from apoptotic bodies can interfere with some assays for apoptosis such as annexin V staining, as they may be close to the size of intact cells, making it difficult to decide where to set the size threshold; (4) irradiated cells display a large increase in nonspecific Ab binding. This may be partly due to an increase in cell size, but, regardless of the cause, it can lead to a mistaken conclusion that there is an increase in a particular antigen if appropriate control reagents are not tested; and (5) experiments utilising Ab crosslinking have neglected the role of cell aggregation, which can cause multiple problems including death from mechanical stress when cells are handled. Consideration of these factors will improve our ability to determine the mode of cell death. PMID- 17342090 TI - The research priorities of patients attending UK cancer treatment centres: findings from a modified nominal group study. AB - Members of the public are increasingly consulted over health care and research priorities. Patient involvement in determining cancer research priorities, however, has remained underdeveloped. This paper presents the findings of the first consultation to be conducted with UK cancer patients concerning research priorities. The study adopted a participatory approach using a collaborative model that sought joint ownership of the study with people affected by cancer. An exploratory, qualitative approach was used. Consultation groups were the main method, combining focus group and nominal group techniques. Seventeen groups were held with a total of 105 patients broadly representative of the UK cancer population. Fifteen areas for research were identified. Top priority areas included the impact cancer has on life, how to live with cancer and related support issues; risk factors and causes of cancer; early detection and prevention. Although biological and treatment related aspects of science were identified as important, patients rated the management of practical, social and emotional issues as a higher priority. There is a mismatch between the research priorities identified by participants and the current UK research portfolio. Current research activity should be broadened to reflect the priorities of people affected by the disease. PMID- 17342091 TI - Variation in the use of chemotherapy in lung cancer. AB - Factors influencing the use of chemotherapy for the initial (6 months) treatment of lung cancer in South East England were investigated. The variables explored as possibly influencing the use of chemotherapy were sex, age, the year of diagnosis, the type of lung cancer, the stage, the index of multiple deprivation and the cancer network of residence. Chi2 analysis and multivariate logistic regression models were used to examine the effect of each of the variables on the use of chemotherapy. The results showed a highly significant trend in use of chemotherapy over time; the adjusted proportion of patients receiving chemotherapy increasing from 13.6% in 1994 to 29.3% in 2003. However, age, cancer network and type of lung cancer had the strongest influence on the use of chemotherapy. This finding is important when we consider that the NHS Cancer Plan aims at improving inequalities in cancer care in the UK. PMID- 17342092 TI - Dual EGFR and mTOR targeting in squamous cell carcinoma models, and development of early markers of efficacy. AB - The epidermal growth factor receptor (EGFR) is a validated target in squamous cell carcinoma (SCC) of the head and neck. Most patients, however, do not respond or develop resistance to this agent. Mammalian target of rapamycin (mTOR) is involved in the pathogenesis of SCC of the head and neck (SCCHN). This study aimed to determine if targeting mTOR in combination with EGFR is effective in SCC, and to develop early pharmacodynamic markers of efficacy. Two SCC cell lines, one resistant (HEP2) and one of intermediate susceptibility (Detroit 562) to EGFR inhibitors, were xenografted in vivo and treated with an mTOR inhibitor (temsirolimus), an EGFR inhibitor (erlotinib) or a combination of both. Temsirolimus exerted superior growth arrest in both cell lines than erlotinib. The combined treatment resulted in synergistic antitumor effects in the Detroit 562 cell line. Immunohistochemical assessment of pharmacodynamic effects in fine needle aspiration (FNA) biopsies early after treatment using phospho MAPK, Phospho-P70 and Ki67 as end points demonstrated pathway abrogation in the Detroit 562 tumours treated with the combination, the only group where regressions were seen. In conclusion, an mTOR inhibitor showed antitumor activity in EGFR resistant SCC cell lines. Marked antitumor effects were associated with dual pathway inhibition, which were detected by early FNA biopsies. PMID- 17342093 TI - Overexpression of HMGA1 promotes anoikis resistance and constitutive Akt activation in pancreatic adenocarcinoma cells. AB - HMGA1 proteins are architectural transcription factors that are overexpressed by pancreatic adenocarcinomas. Roles of HMGA1 in mediating the malignant phenotype of this cancer are poorly understood. We tested the hypothesis that overexpression of HMGA1 promotes resistance to anoikis (apoptosis induced by anchorage deprivation) in pancreatic cancer cells. HMGA1 cDNA was stably transfected into MiaPaCa2 human pancreatic adenocarcinoma cells (which have low baseline expression levels of HMGA1). Cells were grown in suspension on PolyHEMA coated plates and their susceptibility to anoikis was assayed using flow cytometry. Overexpression of HMGA1 was associated with marked reductions in susceptibility to anoikis in concert with increases in Akt phosphorylation (Ser473) and in Akt kinase activity and with reductions in caspase 3 activation. Inhibition of phosphoinositidyl-3 (PI3-K)/Akt pathway with either the small molecule inhibitor LY294002 or dominant-negative Akt resulted in reversal of anoikis resistance induced by HMGA1 overexpression. Further, RNA interference mediated HMGA1 silencing in MiaPaCa2 and BxPC3 (a human pancreatic adenocarcinoma cell line with high baseline levels of HMGA1 expression) cells resulted in significant increases in susceptibility to anoikis. Our findings suggest HMGA1 promotes anoikis resistance through a PI3-K/Akt-dependent mechanism. Given the putative associations between anoikis resistance and metastatic potential, HMGA1 represents a potential therapeutic target in pancreatic adenocarcinoma. PMID- 17342094 TI - High-risk HPV type-specific clearance rates in cervical screening. AB - We assessed clearance rates of 14 high-risk human papillomavirus (hrHPV) types in hrHPV-positive women with normal cytology and borderline/mild dyskaryosis (BMD) in a population-based cervical screening cohort of 44,102 women. The 6-month hrHPV type-specific clearance rates, that is, clearance of the same type as detected at baseline, in women with normal and BMD smears were 43% (95% confidence interval (CI) 39-47) and 29% (95% CI 24-34), respectively. Corresponding 18-month clearance rates were markedly higher, namely 65% (95% CI 60-69) and 41% (95% CI 36-47), respectively. The lowest clearance rates in women with normal cytology were observed for HPV16, HPV18, HPV31, and HPV33. Significantly reduced 18-month clearance rates at a significance level of 1% were observed for HPV16 (49%, 95% CI 41-59) and HPV31 (50%, 95% CI 39-63) in women with normal cytology, and for HPV16 (19%, 95% CI 12-29) in women with BMD. Among women who did not clear hrHPV, women with HPV16 persistence displayed an increased detection rate of >or=CIN3 (normal P<0.0001; BMD, P=0.005). The type specific differences in clearance rates indicate the potential value of hrHPV genotyping in screening programs. Our data support close surveillance (i.e. referral directly, or within 6 months) of women with HPV16 and are inconclusive for surveillance of women with HPV18, HPV31, and HPV33. For the other hrHPV positive women, it seems advisable to adopt a conservative management with a long waiting period, as hrHPV clearance is markedly higher after 18 months than after 6 months and the risk for >or=CIN3 is low. PMID- 17342095 TI - Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma. AB - Glioblastoma multiforme is characterised by invasive growth and frequent recurrence. Here, we have analysed chromosomal changes in comparison to tumour cell aggressiveness and chemosensitivity of three cell lines established from a primary tumour and consecutive recurrences (BTL1 to BTL3) of a long-term surviving glioblastoma patient together with paraffin-embedded materials of five further cases with recurrent disease. Following surgery, the BTL patient progressed under irradiation/ lomustine but responded to temozolomide after re operation to temozolomide. The primary tumour -derived BTL1 cells showed chromosomal imbalances typical of highly aggressive glioblastomas. Interestingly, BTL2 cells established from the first recurrence developed under therapy showed signs of enhanced chromosomal instability. In contrast, BTL3 cells from the second recurrence resembled a less aggressive subclone of the primary tumour. Although BTL2 cells exhibited a highly aggressive phenotype, BTL3 cells were characterised by reduced proliferative and migratory potential. Despite persistent methylation of the O6-methylguanine-DNA methyltransferase promoter, BTL3 cells exhibited the highest temozolomide sensitivity. A comparable situation was found in two out of five glioblastoma patients, both characterised by enhanced survival time, who also relapsed after surgery/chemotherapy with less aggressive recurrences. Taken together, our data suggest that pretreated glioblastoma patients may relapse with highly chemosensitive tumours confirming the feasibility of temozolomide treatment even in case of repeated recurrence. PMID- 17342097 TI - How accurate are formulas that calculate creatinine clearance? PMID- 17342096 TI - Anti-Cripto Mab inhibit tumour growth and overcome MDR in a human leukaemia MDR cell line by inhibition of Akt and activation of JNK/SAPK and bad death pathways. AB - Doxorubicin (DOX) selection of CCRF-CEM leukaemia cell line resulted in multidrug resistance (MDR) CEM/A7R cell line, which overexpresses MDR, 1 coded P glycoprotein (Pgp). Here, we report for the first time that oncoprotein Cripto, a founding member of epidermal growth factor-Cripto-FRL, 1-Criptic family is overexpressed in the CEM/A7R cells, and anti-Cripto monoclonal antibodies (Mab) inhibited CEM/A7R cell growth both in vitro and in an established xenograft tumour in severe combined immunodeficiency mice. Cripto Mab synergistically enhanced sensitivity of the MDR cells to Pgp substrates epirubicin (EPI), daunorubicin (DAU) and non-Pgp substrates nucleoside analogue cytosine arabinoside (AraC). In particular, the combination of anti-Cripto Mab at less than 50% of inhibition concentrations with noncytotoxic concentrations of EPI or DAU inhibited more than 90% of CEM/A7R cell growth. Cripto Mab slightly inhibited Pgp expression, and had little effect on Pgp function, indicating that a mechanism independent of Pgp was involved in overcoming MDR. We demonstrated that anti-Cripto Mab-induced CEM/A7R cell apoptosis, which was associated with an enhanced activity of the c-Jun N-terminal kinase/stress-activated protein kinase and inhibition of Akt phosphorylation, resulting in an activation of mitochondrial apoptosis pathway as evidenced by dephosphorylation of Bad at Ser136, Bcl-2 at Ser70 and a cleaved caspase-9. PMID- 17342098 TI - Is laparoscopic donor nephrectomy the new standard? PMID- 17342099 TI - Too little, too late? AB - To win the fight against bird flu, the World Health Organization must forge partnerships with the governments of developing countries hit hardest by the disease. PMID- 17342101 TI - Biomedical research faces flat budget for 2008. PMID- 17342102 TI - Infrastructure, biotech top African science summit agenda. PMID- 17342103 TI - Activists protest national parks proposal to profit from microbes. PMID- 17342104 TI - AIDS gel's failure calls prevention approach into question. PMID- 17342105 TI - Canceled conference puts conflicts of interest under scrutiny. PMID- 17342106 TI - WikiMedia. PMID- 17342108 TI - Reply to 'Alice Dautry' profile. PMID- 17342109 TI - Do biomarkers trump behavior? PMID- 17342111 TI - The ABCs of beta-cell dysfunction in type 2 diabetes. PMID- 17342112 TI - Cracking the cytokine code in psoriasis. PMID- 17342114 TI - Langerhans cells lap up HIV-1. PMID- 17342115 TI - Long-distance affair with adrenal GRK2 hangs up heart failure. PMID- 17342116 TI - Vaccine leads to memory loss. PMID- 17342117 TI - Regulatory T-cell development: is Foxp3 the decider? PMID- 17342118 TI - A plague upon fibrin. PMID- 17342121 TI - Unlikely partners tackle TB funding woes. PMID- 17342122 TI - After decades of drought, new drug possibilities flood TB pipeline. PMID- 17342123 TI - From TB tests, just a 'yes or no' answer, please. PMID- 17342124 TI - A clash of cultures. PMID- 17342125 TI - Health agency pulls back on 'patronizing' approach to TB treatment. PMID- 17342128 TI - Virtually incurable TB warns of impending disaster. PMID- 17342129 TI - Trials and tribulations. PMID- 17342131 TI - When the vaccine causes disease. PMID- 17342132 TI - A dozen vaccine candidates bring shot of hope to TB epidemic. PMID- 17342133 TI - Profile: Wafaa El-Sadr. PMID- 17342136 TI - The open book of infectious diseases. PMID- 17342137 TI - Defining the 'survivasome' of Mycobacterium tuberculosis. PMID- 17342138 TI - The survival kit of Mycobacterium tuberculosis. PMID- 17342139 TI - Mycobacterium tuberculosis virulence: lipids inside and out. PMID- 17342140 TI - Mycobacterial virulence and specialized secretion: same story, different ending. PMID- 17342142 TI - Challenges in tuberculosis drug research and development. PMID- 17342143 TI - From magic bullets back to the magic mountain: the rise of extensively drug resistant tuberculosis. PMID- 17342144 TI - Changing funding patterns in tuberculosis. PMID- 17342145 TI - Aligning pharmaceutical innovation with medical need. PMID- 17342146 TI - Tuberculosis, a neglected opportunity? PMID- 17342149 TI - Hidden African ancestors: hidden secrets of your ancestors. PMID- 17342150 TI - Comment on 'Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease'. PMID- 17342151 TI - Ring chromosome formation as a novel escape mechanism in patients with inverted duplication and terminal deletion. AB - Ring chromosomes are rare cytogenetic findings and are associated at phenotypic level with mental retardation and congenital abnormalities. Features specific for ring chromosome syndromes often overlap with the features of terminal deletions for the corresponding chromosomes. Here, we report a case of a ring chromosome 14 which was identified by conventional cytogenetics and shown to have a terminal deletion and an additional inverted duplication with a triplication by using large insert clone and oligo array-comparative genomic hybridization (array-CGH), fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA). The combination of an inverted duplication with a terminal deletion in a ring chromosome is of special interest for the described syndromes of chromosome 14. The presented findings might explain partly overlapping clinical features described in terminal deletion, duplication and ring chromosome 14 cases, as these rearrangements can be easily overlooked when performing GTG banding only. Furthermore, we suggest that ring chromosome formation can act as an alternative chromosome rescue next to telomere healing and capture, particularly for acrocentric chromosomes. To our knowledge, this is the first time an inverted duplication with a terminal deletion in a ring chromosome is identified and characterized using high-resolution molecular karyotyping. Systematic evaluation of ring chromosomes by array-CGH might be especially useful in distinguishing cases with a duplication/deletion from those with a deletion only. PMID- 17342152 TI - Diagnostic accuracy of methods for the detection of BRCA1 and BRCA2 mutations: a systematic review. AB - As sequence analysis for BRCA1 and BRCA2 mutations is both time- and cost intensive, current strategies often include scanning techniques to identify fragments containing genetic sequence alterations. However, a systematic assessment of the diagnostic accuracy has been lacking so far. Here, we report on a systematic review to assess the internal and external validity of current scanning techniques. Inclusion criteria were: controlled design, investigators blinded, and tests suitable as a scanning tool for the whole genes BRCA1 and BRCA2. Outcome parameters were sensitivity, specificity, and positive and negative predictive values compared to direct sequencing. Out of 3816 publications, 10 studies reporting on 12 methods met our inclusion criteria. The internal and external validity of most of these studies was limited. Sensitivities were reported to be 100% for enzymatic mutation detection (EMD), multiple-dye cleavase fragment length polymorphism (MD-CFLP), fluorescence-based conformation-sensitive gel electrophoresis (F-CSGE), RNA-based sequencing, restriction endonuclease fingerprinting-single strand conformation polymorphism (REF-SSCP), stop codon (SC) assay, and denaturing high-performance liquid chromatography (DHPLC). Sensitivity was 50-96% for SSCP, 88-91% for two dimensional gene scanning (TDGS), 76% for conformation-sensitive gel electrophoresis (CSGE), 75% for protein truncation test (PTT), and 58% for micronucleus test (MNT). Specificities close to 100% were reported, except for MNT. PTT and SC assay are only able to detect truncating mutations. Most studies were designed to introduce new experimental approaches or modifications of established methods and require further evaluation. F-CSGE, REF-SSCP, RNA-based sequencing, EMD, and MD-CFLP will need further evaluation before their use in a routine setting can be considered. SSCP, MNT, PTT, CSGE, and TDGS cannot be recommended because of their low sensitivity. DHPLC outperforms all other methods studied. However, none of the four studies evaluating DHPLC was performed on BRCA2. PMID- 17342154 TI - Genetic component of identification, intensity and pleasantness of odours: a Finnish family study. AB - Although potential odorant receptor genes have been identified, the precise genetic component of perception of odours is still obscure. Although there is some evidence for heritability of a few olfactory-related traits, no genome-wide search for loci harboring underlying genes has been published to date. We performed a genome-wide scan to identify loci affecting the identification, intensity and pleasantness of 12 odours (cinnamon, turpentine, lemon, smoke, chocolate, rose, paint thinner, banana, pineapple, gasoline, soap, onion) using 146 Finnish adults from 26 families. Several of these traits showed heritable variation in the families. Suggestive evidence of linkage was found for the pleasantness of cinnamon odour (h(2)=61%) on chromosome 4q32.3 (multipoint logarithm of the odds (LOD) score 3.01), as well as for the perceived intensity of paint thinner odour (h(2)=31%) on chromosome 2p14 (multipoint LOD score 2.55). As these loci do not contain any known human odorant receptor genes, they may rather harbor genes that affect the central processing than the peripheral detection of the odour signal. Thus, perception of odours is potentially modified by genes other than those encoding odorant receptors. PMID- 17342155 TI - Relationship between E23K (an established type II diabetes-susceptibility variant within KCNJ11), polycystic ovary syndrome and androgen levels. AB - Polycystic ovary syndrome (PCOS) is strongly associated with hyperinsulinaemia and type II diabetes (T2D). Sequence variation within KCNJ11 (encoding Kir6.2, the beta-cell inwardly rectifying potassium channel) is implicated in the pathogenesis of neonatal diabetes, hyperinsulinaemia of infancy and multifactorial T2D. Comprehensive tagging studies have demonstrated that the KCNJ11 E23K variant (or ABCC8 A1369S in LD>0.9) is responsible for the known association between KCNJ11 and T2D. Given the phenotypic overlap between PCOS and T2D, we investigated whether E23K is involved in susceptibility to PCOS and related traits. Case-control analyses for the KCNJ11 E23K variant were performed in (a) 374 PCOS cases and 2574 controls of UK British/Irish origin, and (b) 550 women with PCOS symptoms and 1114 controls from a Finnish birth cohort. The relationship between E23K genotype and androgen levels (a key intermediate phenotype relevant to PCOS) in 1380 samples was studied. The UK case-control analysis revealed no association between E23K genotypes and PCOS status (P=0.49; Cochran-Armitage test), and no significant relationship between E23K genotype and androgen measures in the samples for which these phenotypes were available (P=0.19). Similarly, the Finnish case-control analysis showed no association between E23K genotypes and PCOS status (P=0.75; Cochran-Armitage test), and no significant relationship between E23K genotype and androgen measures in the samples for which these phenotypes were available (Finnish controls, P=0.25; Finnish cases, P=0.08). In conclusion, these data (involving >4600 subjects) provide no evidence that common variants of the KCNJ11 E23K polymorphism have a major influence on PCOS susceptibility, though modest effect sizes (OR<1.25) cannot be excluded. PMID- 17342156 TI - Angioma serpiginosum with oesophageal papillomatosis is an X-linked dominant condition that maps to Xp11.3-Xq12. AB - We report on a four-generation family with localized subepidermal telangiectasias following Blaschko's lines (angioma serpiginosum). The vascular streaks are present at birth and progress slowly thereafter. In several family members papillomatosis of the entire oesophagus was found to be part of the condition. Mild nail and hair dystrophy added to the resemblance of Goltz-Gorlin syndrome (focal dermal hypoplasia), suggesting that the present condition could be a mild variant. All affected family members are females, there is no increased miscarriage rate, and X-inactivation in affected females is highly skewed, compatible with X-linked dominant inheritance with very early in utero lethality in males. In the family, 11 informative meioses were available to study the segregation of X-chromosome markers. Significant linkage (LOD score 3.31) was found to a region flanked by markers DXS8026 and DXS106 (44-67 Mb from Xpter) that includes the centromere. PMID- 17342157 TI - Heritable skewed X-chromosome inactivation leads to haemophilia A expression in heterozygous females. AB - Factor VIII gene, F8, mutations cause haemophilia A (HA), an X-linked recessive disorder. Expression in heterozygous females has been ascribed to skewed X chromosome inactivation (XCI). To investigate the cause of HA in three heterozygous females within an Atlantic Canadian kindred, the proband (severely affected girl, FVIII activity: 2%) and 17 relatives across three generations were studied. F8 genotype, FVIII activity, XCI ratio (XCIR) (paternal active X: maternal active X), karyotype, submegabase resolution tiling set array competitive genome hybridization (competitive genomic hybridization (SMRT)), and microsatellite analyses were utilized. A positive linear relationship between FVIII activity and percentage-activated normal X-chromosome was found in HA heterozygous females (R(2)=0.87). All affected, but no unaffected females, had an XCIR skewed toward activation of the mutant X-chromosome (proband 92:8, SD 2). Unexpectedly, high numbers of females have dramatically skewed XCIRs (>80:20 or <20:80) (P<0.05). The distribution of XCIR frequencies within this family was significantly different than predicted by normal population data or models of random XCI (P<0.025), with more females having higher degrees of skewing. Known causes of skewing, such as chromosomal abnormalities, selection against deleterious alleles, and X-inactive-specific transcript mutations, are not consistent with our results. This study shows that FVIII activity in HA heterozygous females can be directly related to XCI skewing, and that low FVIII activity in females in this family is due to unfavourable XCI skewing. Further, the findings suggest that these XCI ratios are genetically influenced, consistent with a novel heritable human X controlling element (XCE) functioning similarly to the mouse Xce. PMID- 17342159 TI - Acute renal failure after allogeneic myeloablative stem cell transplantation: retrospective analysis of incidence, risk factors and survival. AB - Acute renal failure (ARF) is an important complication after stem cell transplantation (SCT). We retrospectively analysed ARF in 363 recipients of allogeneic myeloablative SCT to identify incidence, risk factors, associated post transplantation complications and mortality of ARF. ARF was graded as grade 0 (no ARF) to grade 3 (need for dialysis) according to creatinine, estimated glomerular filtration rate and need for dialysis. The incidence of severe renal failure (grades 2 and 3 combined) was 49.6% (180 of 363 patients). Hypertension present at SCT was identified as a risk factor for ARF (P=0.003). Despite this, survival of these patients was not different compared to patients without hypertension. Admission to the intensive care unit (ICU) was a post-transplantation complication significantly associated with ARF (P<0.001). Survival rate was highest in patients with ARF grade 0-1 and lowest in patients with grade 3 (P<0.001). However, after correction for complications associated with high mortality (admission to the ICU, thrombotic thrombocytopenic purpura, sinusoidal occlusion syndrome (SOS) and acute graft-versus-host disease) the significant difference in survival disappeared, showing that ARF without co-morbid conditions has a good prognosis, and ARF with co-morbid conditions has a poor prognosis. This poor prognosis is due to the presence of co-morbid conditions rather than development of ARF itself. PMID- 17342158 TI - High-dose chemotherapy using BEAM without autologous rescue followed by reduced intensity conditioning allogeneic stem-cell transplantation for refractory or relapsing lymphomas: a comparison of delayed versus immediate transplantation. AB - Patients with refractory/relapsing lymphoma are rarely cured by chemotherapy. High-dose chemotherapy (HDC) for tumor debulking followed by reduced-intensity conditioning (RIC) hematopoietic stem-cell transplantation (HSCT) has been advocated as a concept. We previously treated 10 patients (group A) with BEAM chemotherapy followed by delayed RIC HSCT at day 28. We now report on the subsequent 11 patients receiving BEAM followed immediately by fludarabine/total body irradiation and allogeneic HSCT (group B), and compare the outcome to group A patients. Non-hematological toxicity before engraftment was comparable, only gut toxicity was higher in group B. Days in aplasia, days on antibiotics and length of hospital stay were significantly longer in group A. Cumulative incidence of acute (GvHD) >or=grade II and incidence of chronic GvHD were lower in group B. At last follow-up, seven patients in group A were alive, with six of them in complete remission. In group B, nine patients were alive, seven of them in complete remission. No significant difference in estimated 3-year overall survival was seen. These data challenge the initial concept of debulking first and delaying allogeneic RIC HSCT. Allogeneic HSCT with standard BEAM conditioning is a valid alternative for patients with resistant/relapsed lymphoma, which might be considered earlier in the disease course. PMID- 17342160 TI - Coffee consumption, serum gamma-glutamyltransferase and risk of type II diabetes. AB - OBJECTIVES: To study the joint association of coffee consumption and serum gamma glutamyltransferase (GGT) levels on the risk of developing type II diabetes. DESIGN, SETTING AND SUBJECTS: A total of 21,826 Finnish men and women who were 35 74 years of age and without any history of diabetes at baseline (years 1982, 1987, 1992 and 1997) were included in the present analyses. They were prospectively followed up for onset of type II diabetes (n=862 cases), death or until the end of the year 2002. Coffee consumption, serum GGT and other study parameters were determined at baseline using standardized measurements. Analyses were stratified by the serum GGT level classified into two classes using the 75th sex-specific percentiles as the cut point. RESULTS: Coffee consumption was significantly and inversely associated with incident diabetes among both men and women. Serum GGT modified the association between coffee consumption and incident diabetes. Subjects in the high category of coffee consumption with the GGT level > or = 75th percentile showed a significant inverse association for women, and for both sexes combined. The association was not significant in subjects with the GGT level < or = 75th percentile. There was a significant interaction effect of GGT and coffee consumption on risk of type II diabetes in data of women (P=0.05) and in both sexes combined (P=0.02). CONCLUSIONS: Habitual coffee consumption is associated with lower incidence of type II diabetes particularly in those with higher baseline serum GGT levels. PMID- 17342161 TI - High altitude and early childhood growth retardation: new evidence from Tibet. AB - OBJECTIVE: To assess possible effect of high altitude on early childhood growth in Tibet. METHOD: A cross-sectional survey on child health and nutrition was conducted in Tibet with stratified multistage cluster random sampling technique. Height and weight status of Tibetan children <36 months of age was measured. A questionnaire was administered to mothers of children for information on family background, child feeding practice and health care and maternal care. A total of 1458 children with complete information were used for analysis. A logistic regression model was used to control for selected potential confounding factors and then observed altitude effect on growth of Tibetan children. RESULTS: Positive association of stunting with altitude was observed for each age group, even after controlling for selected potential affecting factors. Children above 3500 m had two to six times risk of getting stunting compared with those at 3000 m when socioeconomic and other factors were controlled. Effect of altitude on underweight was observed only among children <24 months old and significant increase in odds ratio appeared only above 4000 m after controlling for those confounding factors. Indicator of wasting was not related to altitude. CONCLUSIONS: Altitude might result in a delay in height of younger Tibetan children, independent of socioeconomic and other factors operating through nutrition and disease, and took adverse effect persistently through birth to 3 years old. Its adverse effect on weight could be limited. For comparison and assessment of nutritional status of Tibetan children, the effect of altitude on growth should be taken into account. PMID- 17342162 TI - Nutritional depletion and its relationship to respiratory impairment in patients with chronic respiratory failure due to COPD or restrictive thoracic diseases. AB - OBJECTIVE: While malnutrition, especially fat-free mass index (FFMI), is a predictor for mortality in chronic obstructive pulmonary disease (COPD), less information on prevalence and mechanisms is available in patients with chronic respiratory failure (CRF) due to restrictive thoracic diseases (RTD). DESIGN AND SETTING: Cross-sectional study of patients consecutively admitted to an in patient primary pulmonary centre. SUBJECTS: One hundred and thirty-two patients (30% RTD; 70% COPD) with CRF and intermittent non-invasive positive pressure ventilation. INTERVENTIONS: Malnutrition was quantified by bioelectrical impedance analysis or body mass index (BMI), and its relationship to laboratory, lung function, inspiratory muscle and blood gas parameters and 6-min walking distance (6-MWD) was assessed. RESULTS: Malnutrition in terms of BMI<20 kg/m(2) occurred in 16.1% of patients with COPD but none of those with RTD. FFMI<17.4 (<15.0 in female patients) kg/m(2) was found in 35.4 and 30.7%, respectively. FFMI was correlated with airway obstruction (sR(aw), r = -0.50; FEV(1)/VC, r = 0.28; P< or = 0.01 each) and lung hyperinflation (intrathoracic gas volume, r = 0.41; total lung capacity (TLC), r = -0.50; P< or = 0.001 each) in COPD, and with lung restriction in RTD (TLC, r=0.40; P=0.011). Furthermore, malnourished patients showed a higher inspiratory load (P (0.1)) and reduced 6-MWD in both groups. In COPD, only hyperinflation and P (0.1) were independently related to FFMI. CONCLUSIONS: Malnutrition as indicated by low FFMI was similarly prevalent in patients with CRF and COPD or RTD, but inadequately represented by BMI. The correlations between lung function impairments specific for the disease and FFMI emphasized the link between malnutrition and respiratory mechanical load irrespective of its aetiology. PMID- 17342163 TI - Holotranscobalamin and methylmalonic acid as prognostic markers following an acute myocardial infarction. AB - OBJECTIVE: To evaluate whether low levels of holotranscobalamin (holoTC) or elevated levels of methylmalonic acid (MMA), both indicators of vitamin B(12) deficiency, might predispose to new cardiovascular events following an acute myocardial infarction (MI). DESIGN: A prospective prognostic study. SETTING: One hospital center in Stavanger, Norway. SUBJECTS: A total of 300 patients admitted with an acute MI. METHODS: Registration of new TnT positive coronary events (defined as TnT>0.05 microg/l and a typical MI pattern) and/or cardiac death during a median follow-up time of 45 months. RESULTS: We compared the recurrence of events in the lowest quartile of holoTC (Q1<73.9 pmol/l) to the event rate above the 25% percentile (Q2-4). For methylmalonic acid (MMA) the same comparison was carried out for the upper quartile (Q4 > or =0.24 micromol/l) as compared with the event rate below the 75% percentile (Q1-3). After 18 and 45 months of follow-up, the odds ratio (OR) for Q1 vs Q2-4 for holoTC was 1.15 (95% confidence interval (CI) 0.91-1.46, P=0.25) and 1.05 (95% CI 0.86-1.29, P=0.64), respectively. For MMA the OR for Q4 vs Q1-3 was 0.95 (95% CI 0.76-1.19, P=0.67) after 18 months and 1.01 (95% CI 0.83-1.23, P=0.90) after 45 months. CONCLUSION: This study showed no increased risk of future cardiovascular events associated with low levels of holoTC or high levels of MMA following an acute MI. PMID- 17342164 TI - How do socio-economic status, perceived economic barriers and nutritional benefits affect quality of dietary intake among US adults? AB - BACKGROUND: Socio-economic factors may affect diet quality, perhaps differentially across gender and ethnicity. The mechanism of this association is still largely unknown. OBJECTIVES: We examined the independent effects of socio economic status (SES), perceived barrier of food price (PBFP) and perceived benefit of diet quality (PBDQ) on diet quality indicators and indices (DQI(j,k)), across gender and ethnicity. Additionally, we estimated the mediation proportion of the effect of SES on DQI(j,k) through PBFP and PBDQ. METHODS: Data from two cross-sectional surveys, the Continuing Survey of Food Intakes by Individuals (CSFII) and Diet and Health Knowledge Survey (DHKS) 1994-96 were used. Our sample consisted of 4356 US adults aged 20-65 years. With principal components analysis, SES (an index) was measured using household income per capita and education, and PBDQ was measured using an 11-item scale. PBFP was defined as the ratio of importance of food price score relative to nutrition. DQI(j,k) were assessed by a set of indicators and two indices including the Healthy Eating Index. RESULTS: The associations between SES, PBFP, PBDQ and DQI(j,k) varied significantly across gender and ethnic groups. PBFP acted as a mediator in the association between SES and selected DQI(j) indicators, namely energy, fat intake, sodium and simple sugar consumption (mediation proportion >10%), but not PBDQ. CONCLUSIONS: SES, PBFP and PBDQ all affect dietary intake, and vary by ethnicity and gender. Positive effect of SES on DQI(j,k) may be mediated by PBFP but not PBDQ which is an independent protective factor. Nutrition education is important to promote healthy eating. PMID- 17342165 TI - Vitamin D status and its association with parathyroid hormone concentrations in women of child-bearing age living in Jakarta and Kuala Lumpur. AB - OBJECTIVE: To describe the vitamin D status of women living in two Asian cities,- Jakarta (6 degrees S) and Kuala-Lumpur (2 degrees N), to examine the association between plasma 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations, and to determine a threshold for plasma 25-hydroxyvitamin D above which there is no further suppression of PTH. Also, to determine whether dietary calcium intake influences the relationship between PTH and 25-hydroxyvitamin D. DESIGN: Cross sectional. SETTING: Jakarta, Indonesia and Kuala Lumpur, Malaysia. PARTICIPANTS: A convenience sample of 504 non-pregnant women 18-40 years. MAIN MEASURES: Plasma 25-hydroxyvitamin D and PTH. RESULTS: The mean 25-hydroxyvitamin D concentration was 48 nmol/l. Less than 1% of women had a 25-hydroxyvitamin D concentration indicative of vitamin D deficiency (<17.5 nmol/l); whereas, over 60% of women had a 25-hydroxyvitamin D concentration indicative of insufficiency (<50 nmol/l). We estimate that 52 nmol/l was the threshold concentration for plasma 25 hydroxyvitamin D above which no further suppression of PTH occurred. Below and above this concentration the slopes of the regression lines were -0.18 (different from 0; P=0.003) and -0.01 (P=0.775), respectively. The relation between vitamin D status and parathyroid hormone concentration did not differ between women with low, medium or high calcium intakes (P=0.611); however, even in the highest tertile of calcium intake, mean calcium intake was only 657 mg/d. CONCLUSION: On the basis of maximal suppression of PTH we estimate an optimal 25-hydroxyvitamin D concentration of approximately 50 nmol/l. Many women had a 25-hydroxyvitamin D below this concentration and may benefit from improved vitamin D status. PMID- 17342166 TI - The associations between current recommendation for physical activity and cardiovascular risks associated with obesity. AB - OBJECTIVE: To examine associations between current recommended physical activity levels and body mass index (BMI) with some cardiovascular disease (CVD) risk factors (total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C), C-reactive protein (CRP), fibrinogen, and blood pressure), general health score (GHQ12) and predicted coronary heart disease (CHD) risk. DESIGN: Further analysis of the cross-sectional Scottish Health Survey 1998 data. SUBJECTS: Five thousand four hundred and sixty adults 16-74 years of age. RESULTS: After controlling for some confounding factors, obesity was significantly associated with higher odds ratio (OR) for elevated cholesterol, CRP, systolic blood pressure, non-HDL-C and lower HDL-C (P<0.001), and with greater predicted CHD risk compared to BMI <25 kg/m(2). Regular self reported physical activity was associated with smaller OR of lower HDL-C and higher CRP, and average predicted 10-year CHD risk in obese subjects, but did not eliminate the higher risk of the measured CVD risk factors in this group. The OR of these two risk factors were still high 4.39 and 2.67, respectively, when compared with those who were inactive with BMI <25 kg/m(2) (P<0.001). Those who reported being physically active had better GHQ scores in all BMI categories (P<0.001). CONCLUSION: Reporting achievement of recommended physical activity levels may reduce some CVD risk factors, predicted CHD risk and improve psychosocial health, but may not eliminate the extra risk imposed by overweight/obesity. Therefore, increasing physical activity and reducing body weight should be considered to tackle CVD risk factors. PMID- 17342167 TI - Association of amphetamine-induced striatal dopamine release and cortisol responses to psychological stress. AB - Preclinical studies have shown that stress and glucocorticoids increase mesolimbic dopamine (DA) and thereby facilitate psychostimulant self administration. The relationship between stress-induced cortisol and mesolimbic DA responses to psychostimulants has not been studied in humans. To test the hypotheses that glucocorticoid responses to psychological stress are correlated with DA and subjective responses to psychostimulants in humans, 25 healthy adults (18-29 years) completed the Trier Social Stress Test (TSST) and two positron emission tomography (PET) scans with high-specific [11C]raclopride. The first scan was preceded by intravenous saline and the second by amphetamine (AMPH). Findings showed that stress-induced cortisol levels were positively associated with AMPH-induced DA release in the ventral striatum and other striatal regions. Subjects with higher cortisol responses to stress also reported more positive subjective drug effects with AMPH than subjects with lower responses. The results are consistent with preclinical findings showing an interrelationship between glucocorticoids and mesolimbic DA dynamics, which may influence psychostimulant self-administration in humans. PMID- 17342168 TI - Aberrant extracellular signal-regulated kinase (ERK) 5 signaling in hippocampus of suicide subjects. AB - Extracellular signal-regulated kinase 5 (ERK5), the newest member of the mitogen activated protein (MAP) kinase family, is regulated differently than the other MAP kinases. Emerging evidence suggest the role of ERK5 signaling in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. The present study investigates whether suicide brain is associated with alterations in components of the ERK5 signaling cascade. In the prefrontal cortex (PFC) and hippocampus of suicide subjects (n=28) and nonpsychiatric control subjects (n=21), we examined the catalytic activities and protein levels of ERK5 and upstream MAP kinase kinase MEK5 in various subcellular fractions; mRNA levels of ERK5 in total RNA; and DNA-binding activity of myocyte enhancer factor (MEF)2C, a substrate of ERK5. In the hippocampus of suicide subjects, we observed that catalytic activity of ERK5 was decreased in cytosolic and nuclear fractions, whereas catalytic activity of MEK5 was decreased in the total fraction. Further, decreased mRNA and protein levels of ERK5, but no change in protein level of MEK5 were noted. A decrease in MEF2C-DNA-binding activity in the nuclear fraction was also observed. No significant alterations were noted in the PFC of suicide subjects. The observed changes were not related to a specific psychiatric diagnosis. Our findings of reduced activation and/or expression of ERK5 and MEK5, and reduced MEF2C-DNA-binding activity demonstrate abnormalities in ERK5 signaling in hippocampus of suicide subjects and suggest possible involvement of this aberrant signaling in pathogenic mechanisms of suicide. PMID- 17342169 TI - Modulation of the acoustic startle response by the level of arousal: comparison of clonidine and modafinil in healthy volunteers. AB - A sudden loud sound evokes an electromyographic (EMG) response from the orbicularis oculi muscle in humans together with an auditory evoked potential (AEP) and an increase in skin conductance (SC). Startle responses are inhibited by weak prepulses (prepulse inhibition, (PPI)) and may also be modified by the level of alertness. We compared the sedative drug clonidine and the alerting drug modafinil on sound-evoked EMG, AEP, and SC responses, on the PPI of these responses and on level of arousal and autonomic functions. Sixteen healthy male volunteers participated in four weekly sessions (clonidine 0.2 mg, modafinil 400 mg, their combination, placebo) in a double-blind, cross-over, balanced design. Responses were evoked by sound pulses of 115 and 85 dB (PPI) for 40 ms and recorded conventionally. Level of alertness, autonomic functions (pupil diameter, blood pressure, heart rate, salivation, temperature) and the plasma levels of the hormones prolactin, thyroid-stimulating hormone and growth hormone were also measured. Data were analyzed with analysis of variance with multiple comparisons. Both prepulses and clonidine attenuated all three startle responses and modafinil antagonized clonidine's effects on the EMG and AEP responses. None of the drugs affected PPI. Clonidine showed sedative and sympatholytic effects, and modafinil showed alerting and sympathomimetic effects. In conclusion, startle responses were susceptible not only to PPI but also to the level of arousal. PMID- 17342170 TI - Nature and nurture predispose to violent behavior: serotonergic genes and adverse childhood environment. AB - Aggressive behavior is influenced by variation in genes of the serotonergic circuitry and early-life experience alike. The present study aimed at investigating the contribution of polymorphisms shown to moderate transcription of two genes involved in serotonergic neurotransmission (serotonin transporter, 5HTT, and monoamine oxidase A, MAOA) to the development of violence and to test for gene-environment interactions relating to adverse childhood environment. A cohort of 184 adult male volunteers referred for forensic assessment participated in the study. Each individual was assigned to either a violent or a nonviolent group. Logistic regression was performed and the best-fitting model, with a predictive power of 74%, revealed independent effects of adverse childhood environment and MAOA genotype. High environmental adversity during childhood was associated significantly with violent behavior. Forty-five percent of violent, but only 30% of nonviolent individuals carried the low-activity, short MAOA allele. Most interestingly, an interaction effect between childhood environment and 5HTT genotype on violent behavior was found in that high adversity during childhood impacted only the later-life violence if the short promoter alleles were present. These findings indicate complex interactions between genetic variation of the serotonergic circuitry and environmental factors arguing against simplistic, mono-causal explanations of violent behavior. PMID- 17342171 TI - Increasing the levels of insulin-like growth factor-I by an IGF binding protein inhibitor produces anxiolytic and antidepressant-like effects. AB - The present studies were conducted to determine if increasing central levels of the neurotrophic factor insulin-like growth factor-1 (IGF-I) either directly or indirectly produces anxiolytic and antidepressant-like effects in the mouse. Central levels of IGF-I can be increased directly, by administering IGF-I, or indirectly by blocking the insulin-like growth factor binding proteins (IGFBPs). The IGFBP family has the unique ability to regulate IGF-I levels by sequestering IGF-I into an inactive complex. Therefore, an IGFBP inhibitor increases the level of IGF-I available to bind to its receptor. Intracerebroventricular (icv) administration of the nonspecific IGFBP inhibitor NBI-31772 (10-30 microg) increases the number of punished crossings in the four-plate test and NBI-31772 (0.3-10 microg) increases time spent in the open quadrant of the elevated zero maze (EZM), indicative of anxiolytic-like effects. NBI-31772 (3-30 microg) also decreases immobility time in the tail suspension test, indicative of antidepressant-like effects. Similarly, icv administration of IGF-I (0.1 microg) produces anxiolytic-like effects in the four-plate test and IGF-1 (0.3-1 microg) produces anxiolytic-like effects in the EZM. IGF-I (10 microg) also produces antidepressant-like effects in the tail suspension test. Coadministration of the IGF-I receptor antagonist JB1 with NBI-31772 or IGF-I blocks the anxiolytic-like and antidepressant-like effects of these compounds. These results suggest that NBI-31772 produces behavioral effects by increasing levels of IGF-I that in turn activate the IGF-I receptor. The present studies demonstrate that an IGFBP inhibitor mimics the behavioral effects of IGF-I and that IGFBP inhibition may represent a novel mechanism by which to increase IGF-I to treat depression and anxiety. PMID- 17342172 TI - Parallel loss of hippocampal LTD and cognitive flexibility in a genetic model of hyperdopaminergia. AB - Dopamine-mediated neurotransmission has been implicated in the modulation of synaptic plasticity and in the mechanisms underlying learning and memory. In the present study, we tested different forms of activity-dependent neuronal and behavioral plasticity in knockout mice for the dopamine transporter (DAT-KO), which constitute a unique genetic model of constitutive hyperdopaminergia. We report that DAT-KO mice exhibit slightly increased long-term potentiation and severely decreased long-term depression at hippocampal CA3-CA1 excitatory synapses. Mutant mice also show impaired adaptation to environmental changes in the Morris watermaze. Both the electrophysiological and behavioral phenotypes are reversed by the dopamine antagonist haloperidol, suggesting that hyperdopaminergia is involved in these deficits. These findings support the modulation by dopamine of synaptic plasticity and cognitive flexibility. The behavioral deficits seen in DAT-KO mice are reminiscent of the deficits in executive functions observed in dopamine-related neuropsychiatric disorders, suggesting that the study of DAT-KO mice can contribute to the understanding of the molecular basis of these disorders. PMID- 17342173 TI - Repair of neural pathways by olfactory ensheathing cells. AB - Damage to nerve fibre pathways results in a devastating loss of function, due to the disconnection of nerve fibres from their targets. However, some recovery does occur and this has been correlated with the formation of new (albeit abnormal) connections. The view that an untapped growth potential resides in the adult CNS has led to various attempts to stimulate the repair of disconnectional injuries. A key factor in the failure of axonal regeneration in the CNS after injury is the loss of the aligned glial pathways that nerve fibres require for their elongation. Transplantation of cultured adult olfactory ensheathing cells into lesions is being investigated as a procedure to re-establish glial pathways permissive for the regeneration of severed axons. PMID- 17342174 TI - Molecular mechanisms of memory reconsolidation. AB - Memory reconsolidation has been argued to be a distinct process that serves to maintain, strengthen or modify memories. Specifically, the retrieval of a previously consolidated memory has been hypothesized to induce an additional activity-dependent labile period during which the memory can be modified. Understanding the molecular mechanisms of reconsolidation could provide crucial insights into the dynamic aspects of normal mnemonic function and psychiatric disorders that are characterized by exceptionally strong and salient emotional memories. PMID- 17342175 TI - Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice. AB - Increased generation of reactive oxygen species (ROS) leads to oxidative stress in diabetes. Catalase is a highly conserved heme-containing protein that reduces hydrogen peroxide to water and oxygen and is an important factor decreasing cellular injury owing to oxidative stress. Hyperglycemic conditions increase oxidative stress and angiotensinogen gene expression. Angiotensinogen conversion to angiotensin II leads to a furtherance in oxidative stress through increased generation of reactive oxygen species. In this study, we utilized mice transgenically overexpressing rat catalase in a kidney-specific manner to determine the impact on ROS, angiotensinogen and apoptotic gene expression in proximal tubule cells of diabetic animals. Proximal tubules isolated from wild type and transgenic animals without or with streptozotocin-induced diabetes were incubated in low glucose media in the absence or presence of angiotensin II or in a high-glucose media. Our results show that the overexpression of catalase prevents the stimulation of ROS and angiotensinogen mRNA in tubules owing to elevated glucose or angiotensin II in vitro. Additionally, overexpression of catalase attenuated ROS generation, angiotensinogen and proapoptotic gene expression and apoptosis in the kidneys of diabetic mice in vivo. Our studies point to an important role of ROS in the pathophysiology of diabetic nephropathy. PMID- 17342176 TI - Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels. AB - Immunoglobulin A (IgA) nephropathy is the most prevalent form of glomerulonephritis worldwide. A renal biopsy is required for an accurate diagnosis, as no convenient biomarker is currently available. We developed a serological test based upon the observation that this nephropathy is characterized by undergalactosylated IgA1 in the circulation and in mesangial immune deposits. In the absence of galactose, the terminal saccharide of O-linked chains in the hinge region of IgA1 is terminal or sialylated N acetylgalactosamine. A lectin from Helix aspersa, recognizing N acetylgalactosamine, was used to develop an enzyme-linked immunosorbent assay that measures galactose-deficient IgA1 in serum. The median serum lectin-binding IgA1 level was significantly higher for 153 Caucasian adult patients with IgA nephropathy without progression to end-stage renal disease as compared with that for 150 healthy Caucasian adult controls. As the lectin-binding IgA1 levels for the controls were not normally distributed, the 90th percentile was used for determination of significant elevation. Using a value of 1076 U/ml as the upper limit of normal, 117 of the 153 patients with IgA nephropathy had an elevated serum lectin-binding IgA1 level. The sensitivity as a diagnostic test was 76.5%, with specificity 94%; the positive predictive value was 88.6% and the negative predictive value was 78.9%. We conclude that this lectin-binding assay may have potential as a noninvasive diagnostic test for IgA nephropathy. PMID- 17342177 TI - Phenotypic transitions and fibrosis in diabetic nephropathy. AB - The cause of renal fibrosis in diabetic nephropathy is widely believed to be phenotypic switching of fibroblasts to an activated state. However, emerging evidence suggests that diabetes also alters the phenotype of normal, non fibroblast kidney cells, such as mesangial cells, tubular epithelial cells, and bone marrow-derived progenitors. Experiments have shown that cytokines, high glucose, and advanced glycation end products induce profibrotic changes in kidney cell phenotype by the processes of myofibroblast transdifferentiation and epithelial-mesenchymal transition. As a result, differentiated kidney cells become reprogrammed to secrete and accumulate extracellular matrix. This revised view implies that inhibiting phenotypic transitions in nonfibroblasts might limit fibrosis in diabetic nephropathy. PMID- 17342178 TI - Association of serum fetuin-A levels with mortality in dialysis patients. AB - Calcifying atherosclerosis is an active process, which is controlled by calcification inhibitors and inducers. Fetuin-A, an acute phase glycoprotein, is one of the more powerful circulating inhibitors of hydroxyapatite formation. A prospective multicenter cohort study was initiated to include both hemodialysis (HD) and peritoneal dialysis (PD) patients in an evaluation of the association of serum fetuin-A levels with both cardiovascular (CV) and non-CV mortality. An increase in the serum fetuin-A concentration of 0.1 g/l was associated with a significant reduction in all-cause mortality of 13%. There was a significant 17% reduction in non-CV mortality and a near significant reduction in CV mortality. This association of fetuin-A and mortality rates was comparable in both HD and PD patients even when corrected for factors, including but not limited to age, gender, primary kidney disease, C-reactive protein levels, and nutritional status. We conclude that serum fetuin-A concentrations may be a general predictor of mortality in dialysis patients. PMID- 17342179 TI - Pathogenesis of poststreptococcal glomerulonephritis a century after Clemens von Pirquet. AB - Considerable insight has been gained into the etiopathogenesis of poststreptococcal glomerulonephritis since the landmark theoretical construct of Clemens von Pirquet postulated that disease-causing immune complexes were responsible for the nephritis that followed scarlet fever. Over the years, molecular mimicry between streptococcal products and renal components, autoimmune reactivity and several streptococcal antigens have been extensively studied. Recent investigations assign a critical role to both in situ formation and deposition of circulating immune complexes that would trigger a variety of effector mechanisms. Glomerular plasmin-binding activity of streptococcal glyceraldehyde-3-phosphate-dehydrogenase may play a role in nephritogenicity and streptococcal pyrogenic exotoxin B and its zymogen precursor may be the long sought nephritogenic antigen. PMID- 17342180 TI - Neutrophil gelatinase-associated lipocalin as the real-time indicator of active kidney damage. AB - Neutrophil gelatinase-associated lipocalin (Ngal, 24p3, SIP24, lipocalin 2, or siderocalin) was originally purified from neutrophils, but with unknown function. Recently, it was identified that Ngal activates nephron formation in the embryonic kidney, is rapidly and massively induced in renal failure and possesses kidney-protective activity. We would like to propose that blood, urine, and kidney Ngal levels are the real-time indicators of active kidney damage, rather than one of many markers of functional nephron number (as Forest Fire Theory). Ngal is a novel iron-carrier protein exerting pleiotropic actions including the upregulation of epithelial marker E-cadherin expression, opening an exciting field in cell biology. PMID- 17342181 TI - Restricted intake of dietary advanced glycation end products retards renal progression in the remnant kidney model. AB - Diet-derived advanced glycation end products (AGEs) contribute significantly to accumulation of AGEs in renal insufficiency. To test whether modulation of dietary AGEs would impact on progression of chronic renal disease, 5/6 nephrectomy rats were randomly placed on three diets that differed only in AGEs content (low AGEs diet (LAD), high AGEs diet (HAD), and standard rodent diet (SRD)) for 5-13 weeks. Compared with SRD- or HAD-fed rats, LAD-treated animals showed decreased proteinuria and retarded decline of creatinine clearance without alteration of blood pressure. Glomerular volume was reduced by 23% compared with HAD-fed rats at week 13 (P<0.001). Renal fibrosis progressed with time in the remnant kidneys from HAD-fed rats. However, LAD-fed animals presented a better preserved structure of the kidneys. LAD-fed rats demonstrated significantly decreased serum and renal AGEs concentration (P<0.01 and P<0.01). This was associated with marked decrease of intrarenal advanced oxidation protein products and thiobarbituric acid reactive substances, as well as increase of glutathione peroxidase activity. LAD treatment also downregulated expression of monocyte chemoattractant protein-1 and transforming growth factor-1 and ameliorated macrophage infiltration in the remnant kidney. These results demonstrated that restriction of dietary AGEs intake retards progression of renal fibrosis and dysfunction in the remnant kidney model. PMID- 17342182 TI - Possible mechanism of efferent arteriole (Ef-Art) tubuloglomerular feedback. AB - Adenosine triphosphate (ATP) is liberated from macula densa cells in response to increased tubular NaCl delivery. However, it is not known whether ATP from the macula densa is broken down to adenosine, or whether this adenosine mediates efferent arteriole (Ef-Art) tubuloglomerular feedback (TGF). We hypothesized that increased macula densa Ca(2+), release of ATP and degradation of ATP to adenosine are necessary for Ef-Art TGF. Rabbit Ef-Arts and adherent tubular segments (with the macula densa) were simultaneously microperfused in vitro while changing the NaCl concentration at the macula densa. The Ef-Art was perfused orthograde through the end of the afferent arteriole (Af-Art). In Ef-Arts preconstricted with norepinephrine (NE), increasing NaCl concentration from 10 to 80 mM at the macula densa dilated Ef-Arts from 7.5+/-0.7 to 11.1+/-0.3 microm. Buffering increases in macula densa Ca(2+) with the cell-permeant Ca(2+) chelator BAPTA-AM diminished Ef-Art TGF from 3.1+/-0.3 to 0.1+/-0.2 microm. Blocking adenosine formation by adding alpha-beta-methyleneadenosine 5'-diphosphate (MADP) blocked Ef-Art TGF from 2.9+/-0.5 to 0.1+/-0.2 microm. Increasing luminal NaCl at the macula densa from 10 to 45 mM caused a moderate Ef-Art TGF response, 1.3+/-0.1 microm. It was potentiated to 4.0+/-0.3 microm by adding hexokinase, which enhances conversion of ATP into adenosine. Our data show that in vitro changes in macula densa Ca(2+) and ATP release are necessary for Ef-Art TGF. ATP is broken down to form adenosine, which mediates signal transmission of Ef-Art TGF. PMID- 17342183 TI - Clinical presentation of myocardial infarction contributes to lower use of coronary angiography in patients with chronic kidney disease. AB - Patients with chronic kidney disease (CKD) have high mortality following myocardial infarction (MI), but are less likely to undergo coronary angiography than those without CKD. Whether this phenomenon is explained by differences in the presentation of MI or by bias against performing coronary angiography in patients with CKD is unclear. We examined the clinical presentation of 1876 elderly patients who presented with MI and categorized them by estimated glomerular filtration rate: >60 ml/min (no/mild CKD), 30-60 ml/min (CKD Stage 3) or <30 ml/min (CKD Stage 4/5). Compared with patients with no/mild CKD, patients with CKD Stage 3 or Stage 4/5 had more comorbidity, greater prior nursing home use, and higher frequency of conduction abnormalities or anterior infarction. By contrast, peak creatinine kinase-MB fraction (CK-MB) concentrations were lower and ST-elevation MI was less common in patients with CKD Stage 3 or Stage 4/5. In univariate analyses, patients with CKD Stage 4/5 (odds ratio (OR)=0.34, 95% confidence interval (CI): 0.23-0.50) or Stage 3 (OR=0.57, 95% CI: 0.45-0.73) were markedly less likely to undergo angiography than subjects with no/mild CKD. After multivariable adjustment, the association of CKD Stage 3 with the use of coronary angiography was attenuated (OR=0.78, 95% CI: 0.60-1.03), but CKD Stage 4/5 remained strongly associated with lower use (OR=0.52, 95% CI: 0.34-0.80). Clinical features of MI are different in patients with and without CKD and may partly explain the low use of angiography in patients with CKD Stage 3. However, the clinical features of MI do not account for its underuse in MI patients with CKD Stages 4/5. Whether reduced use of angiography in patients with advanced CKD is justified must be evaluated in formal risk-benefit analyses. PMID- 17342184 TI - Regulation of histone methylation by demethylimination and demethylation. AB - Histone methylation has important roles in regulating transcription, genome integrity and epigenetic inheritance. Historically, methylated histone arginine and lysine residues have been considered static modifications because of the low levels of methyl-group turnover in chromatin. The recent identification of enzymes that antagonize or remove histone methylation has changed this view and now the dynamic nature of these modifications is being appreciated. Here, we examine the enzymatic and structural basis for the mechanisms that these enzymes use to counteract histone methylation and provide insights into their substrate specificity and biological function. PMID- 17342185 TI - Helping Wingless take flight: how WNT proteins are secreted. AB - How functional WNT proteins are made and how their secretion is regulated is becoming a focal point for the WNT-signalling field. Recently, lipoprotein particles, WNT lipid modifications, the conserved transmembrane protein Wntless (WLS; also known as EVI and SRT) and the retromer complex have been implicated in WNT secretion. Our aim is to synthesize ideas from these new findings for the mechanisms that underlie WNT secretion. PMID- 17342188 TI - Ataxia rating scales in the balance. PMID- 17342189 TI - Shortage of human intravenous immunoglobulin--reasons and possible solutions. PMID- 17342190 TI - X-linked adrenoleukodystrophy. AB - X-linked adrenoleukodystrophy (X-ALD) is caused by a defect in the gene ABCD1, which maps to Xq28 and codes for a peroxisomal membrane protein that is a member of the ATP-binding cassette transporter superfamily. X-ALD is panethnic and affects approximately 1:20,000 males. Phenotypes include the rapidly progressive childhood, adolescent, and adult cerebral forms; adrenomyeloneuropathy, which presents as slowly progressive paraparesis in adults; and Addison disease without neurologic manifestations. These phenotypes are frequently misdiagnosed, respectively, as attention-deficit hyperactivity disorder (ADHD), multiple sclerosis, or idiopathic Addison disease. Approximately 50% of female carriers develop a spastic paraparesis secondary to myelopathic changes similar to adrenomyeloneuropathy. Assays of very long chain fatty acids in plasma, cultured chorion villus cells and amniocytes, and mutation analysis permit presymptomatic and prenatal diagnosis, as well as carrier identification. The timely use of these assays is essential for genetic counseling and therapy. Early diagnosis and treatment can prevent overt Addison disease, and significantly reduce the frequency of the severe childhood cerebral phenotype. A promising new method for mass newborn screening has been developed, the implementation of which will have a profound effect on the diagnosis and therapy of X-ALD. PMID- 17342191 TI - Olfactory ensheathing cell transplantation as a strategy for spinal cord repair- what can it achieve? AB - Restoring function to the injured spinal cord represents one of the most formidable challenges in regenerative medicine. Glial cell transplantation is widely considered to be one of the most promising therapeutic strategies, and several differentiated glial cell types-in particular, Schwann cells and olfactory ensheathing cells (OECs)-have been proposed as transplant candidates. In this Review, we analyze evidence from animal studies for improved functional recovery following transplantation of OECs into spinal cord injuries, and examine the mechanisms by which repair might be achieved. Data obtained using various injury models support the view that OEC transplants can promote functional recovery, but accumulating anatomical evidence indicates that although axons regenerate within a transplant, they do not cross the lesion or reconnect with neurons on the opposite side to any significant extent. Consequently, it is possible that neuroprotection and promotion of sprouting from intact fibers are the main mechanisms that contribute to functional recovery. We conclude that for the foreseeable future the clinical benefits of OEC transplants alone are likely to be modest. The future potential of cell transplantation strategies will probably depend on the success with which the transplants can be combined with other, synergistic, therapies to achieve significant regeneration of axons and re establish functionally useful connections across a spinal cord injury. PMID- 17342192 TI - Mechanisms of disease: DNA repair defects and neurological disease. AB - In this Review, familial and sporadic neurological disorders reported to have an etiological link with DNA repair defects are discussed, with special emphasis placed on the molecular link between the disease phenotype and the precise DNA repair defect. Of the 15 neurological disorders listed, some of which have symptoms of progeria, six--spinocerebellar ataxia with axonal neuropathy-1, Huntington's disease, Alzheimer's disease, Parkinson's disease, Down syndrome and amyotrophic lateral sclerosis--seem to result from increased oxidative stress, and the inability of the base excision repair pathway to handle the damage to DNA that this induces. Five of the conditions (xeroderma pigmentosum, Cockayne's syndrome, trichothiodystrophy, Down syndrome, and triple-A syndrome) display a defect in the nucleotide excision repair pathway, four (Huntington's disease, various spinocerebellar ataxias, Friedreich's ataxia and myotonic dystrophy types 1 and 2) exhibit an unusual expansion of repeat sequences in DNA, and four (ataxia-telangiectasia, ataxia-telangiectasia-like disorder, Nijmegen breakage syndrome and Alzheimer's disease) exhibit defects in genes involved in repairing double-strand breaks. The current overall picture indicates that oxidative stress is a major causative factor in genomic instability in the brain, and that the nature of the resulting neurological phenotype depends on the pathway through which the instability is normally repaired. PMID- 17342193 TI - Urgent intervention to reduce functional deficits after postoperative stroke. AB - BACKGROUND: A 67-year-old right-handed man with a history of atrial fibrillation developed sudden aphasia after urological surgery. Initial diffusion-weighted and perfusion-weighted MRI demonstrated an area of hypoperfusion in Broca's area, with minimal infarction. INVESTIGATIONS: Neurological examination, language testing and brain MRI scans with diffusion-weighted and perfusion-weighted imaging. DIAGNOSIS: Acute cardioembolic stroke with minimal infarction in Broca's area and a surrounding region of potentially salvageable, hypoperfused cortex. MANAGEMENT: Saline-induced hypertension resulting in rapid restoration of cortical perfusion and a resolution of the initial speech and language deficits. The utility of perfusion-weighted imaging in selecting appropriate candidates for urgent treatment of stroke when thrombolysis is contraindicated is discussed. PMID- 17342194 TI - NTP toxicity studies of sodium dichromate dihydrate (CAS No. 7789-12-0) administered in drinking water to male and female F344/N rats and B6C3F1 mice and male BALB/c and am3-C57BL/6 mice. AB - Sodium dichromate dihydrate is one of a number of inorganic compounds containing hexavalent chromium (CR VI) found in drinking water supplies as a contaminant resulting from various industrial processes including electroplating operations, leather tanning, and textile manufacturing. Because of the lack of adequate experimental data on the toxicity and carcinogenicity of hexavalent chromium ingested orally, and because hexavalent chromium has been found in human drinking water supplies, the California Congressional delegation and the California Environmental Protection Agency nominated hexavalent chromium to the NTP for study. In study 1, male and female F344/N rats and B6C3F1 mice were exposed to sodium dichromate dihydrate (greater than 99% pure) in drinking water for 3 months. In study 2, sodium dichromate dihydrate was administered in drinking water to male B6C3F1, BALB/c, and am3-C57BL/6 mice for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. In study 1, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were given drinking water containing 0, 62.5, 125, 250, 500, or 1,000 mg sodium dichromate dihydrate/L for 3 months (equivalent to average daily doses of approximately 5, 10, 17, 32, or 60 mg sodium dichromate dihydrate/kg body weight to rats and 9, 15, 26, 45, or 80 mg/kg to mice). On a molecular weight basis, these doses are equivalent to approximately 1.7, 3.5, 5.9, 11.2, and 20.9 mg hexavalent chromium/kg body weight per day to rats and 3.1, 5.2, 9.1, 15.7, and 27.9 mg/kg per day to mice. Additional groups of 10 rats per sex were exposed to the same concentrations of sodium dichromate dihydrate for 4 weeks. All rats and mice survived to the end of the study. Reduced body weights occurred in 500 and 1,000 mg/L male rats, 1,000 mg/L female rats, and in male and female mice exposed to 125 mg/L or greater. Water consumption by male and female rats exposed to 250 mg/L or greater and male and female mice exposed to 125 mg/L or greater was generally less than that by the control groups, and decreases in urine volume and increases in urine specific gravity in rats were related to reduced water consumption. Exposure to sodium dichromate dihydrate caused a microcytic hypochromic anemia in rats and mice, but the severity was less in mice. Serum cholesterol and triglyceride concentrations were decreased in rats. Increased bile acid concentrations in exposed groups of rats may have been due to altered hepatic function. The incidences of histiocytic cellular infiltration were generally significantly increased in the duodenum of rats and mice, the liver of female rats, and the mesenteric lymph node of mice exposed to 125 mg/L or greater. Significantly increased nonneoplastic lesions (focal ulceration, regenerative epithelial hyperplasia, and squamous epithelial metaplasia) occurred in the glandular stomach of male and female rats exposed to 1,000 mg/L. Incidences of epithelial hyperplasia of the duodenum were significantly increased in all exposed groups of mice. In study 2, sodium dichromate dihydrate was administered in drinking water to groups of 10 male B6C3F1, 10 male BALB/c, and five male am3-C57BL/6 mice for 3 months at exposure concentrations of 0, 62.5, 125, or 250 mg/L (equivalent to average daily doses of approximately 8, 15, or 25 mg/kg sodium dichromate dihydrate or 2.8, 5.2, or 8.7 mg/kg chromium to B6C3F1, BALB/c, and am3-C57BL/6 mice). All mice in study 2 survived until study termination. Mean body weights of 125 and 250 mg/L B6C3F1 and BALB/c mice and all exposed groups of am3-C57BL/6 mice were less than those of the control groups. Mice exposed to 250 mg/L consumed less water than the control groups. Exposure concentration-related decreases in mean red cell volumes and mean red cell hemoglobin values were observed in all three mouse strains. Erythrocyte counts were increased in exposed B6C3F1 and BALB/c mice but not in am3-C57BL/6 mice. Changes in organ weights were generally consistent with reduced body weights in exposed groups in all mouse strains. No biologically significant differences in reproductive parameters were observed in any strain. Histiocytic cellular infiltration and epithelial hyperplasia of the duodenum occurred in most mice exposed to 125 or 250 mg/L, and the incidences of these lesions were increased in the 62.5 mg/L group compared to controls. Secretory depletion was present in the pancreas of most mice exposed to 125 or 250 mg/L. The incidences of glycogen depletion of the liver were significantly increased in male B6C3F1 mice exposed to 125 or 250 mg/L and in all exposed groups of male am3-C57BL/6 mice. The incidence of histiocytic cellular infiltration in the mesenteric lymph node was significantly increased in the 250 mg/L group of male am3-C57BL/6 mice. Sodium dichromate dihydrate was mutagenic in S. typhimurium strains TA100 and TA98 and in E. coli strain WP2 uvrA pKM101 with and without induced rat liver S9 enzymes. The results of four micronucleus tests conducted in the three strains of mice from studies 1 and 2 were mixed. In study 1, no significant increases were seen in micronucleated normochromatic erythrocytes in peripheral blood samples from male or female B6C3F1 mice; there was a decrease in the percentage of polychromatic erythrocytes among total erythrocytes (an indication of bone marrow toxicity), but the changes were small and not well correlated with exposure concentrations. In study 2, a significant exposure concentration-related increase (P<0.001) in micronucleated normochromatic erythrocytes was seen in am3-C57BL/6 male mice. An equivocal increase in micronucleated erythrocytes was noted in male B6C3F1 mice, based on a small increase in micronucleated normochromatic erythrocytes that did not reach statistical significance. No increase in micronucleated normochromatic erythrocytes was observed in male BALB/c mice. No significant effect of sodium dichromate dihydrate exposure on the percentage of polychromatic erythrocytes was observed in any of the three micronucleus tests conducted in study 2. In summary, administration of sodium dichromate dihydrate in the drinking water to F344/N rats and B6C3F1 mice resulted in focal ulceration, hyperplasia, and metaplasia in the glandular stomach at the limiting ridge in rats in the 1,000 mg/L group and evidence of increased histiocytic infiltration in the liver (female), duodenum of the small intestine, and/or pancreatic lymph nodes at concentrations as low as 62.5 mg/L, the lowest concentration studied. In addition, a microcytic, hypochromic anemia occurred at all exposure concentrations and was considered evidence of a toxic response resulting from absorption of Cr VI following oral ingestion in rats. A similar, but less severe, anemia was evident in mice receiving drinking water containing sodium dichromate dihydrate; histiocytic infiltration was noted in the duodenum of all three strains studied (B6C3F1, BALB/c, and am3-C57BL/6) at all concentrations employed, in the mesenteric lymph nodes at 125 mg/L or greater in the B6C3F1 strain, and at 250 mg/L in the am3-C57BL/6 strain. There was no consistent evidence of hepatocyte injury in mice in any of the strains tested. Variations in glycogen content were considered more likely related to diminished food intake than to the toxicity of sodium dichromate dihydrate. Synonyms: Chromic acid; dichromic acid; disodium salt, dihydrate; disodium dichromate dihydrate; chromium VI. PMID- 17342195 TI - Toxicology and carcinogenesis studies of a mixture of 2,3,7,8-tetrachlorodibenzo p-dioxin (TCDD) (Cas No. 1746-01-6), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (Cas No. 57117-31-4), and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) (Cas No. 57465-28-8) in female Harlan Sprague-Dawley rats (gavage studies). AB - DIOXIN TOXIC EQUIVALENCY FACTOR EVALUATION OVERVIEW: Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds" (DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized, they accumulate in body tissues, mainly adipose, resulting in chronic lifetime human exposure. Since human exposure to DLCs always involves a complex mixture, the toxic equivalency factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally related polychlorinated biphenyls (PCBs) and mixtures of these compounds. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 3,3',4,4',5 pentachlorobiphenyl (PCB 126) are not manufactured commercially other than for scientific research purposes. The main sources of TCDD and PeCDF releases into the environment are from metal smelting, refining, and processing; combustion and incineration sources; chemical manufacturing and processing; biological and photochemical processes; and existing reservior sources that reflect past releases. PCB mixtures were commercially produced and used in the electric power industry as dielectric insulating fluids in transformers and capacitors and used in hydraulic fluids, plastics, and paints. TCDD, PeCDF, and PCB 126 were selected for study by the National Toxicology Program as part of the dioxin TEF evaluation to assess the cancer risk posed by complex mixtures of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and PCBs. The dioxin TEF evaluation includes conducting multiple 2-year rat bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLC's, structurally related PCBs, and mixtures of these compounds. Female Harlan Sprague-Dawley rats were administered a mixture of TCDD, PeCDF, and PCB 126 (henceforth referred to as the TEF mixture) in corn oil:acetone (99:1) by gavage for 14, 31, or 53 weeks or 2 years. While one of the aims of the dioxin TEF evaluation was a comparative analysis across studies, in this Technical Report only the results of the present study of the mixture of TCDD, PeCDF, and PCB 126 are presented and discussed. 2 YEAR STUDY: Groups of 81 female rats were administered 10, 22, 46, or 100 ng toxic equivalents (TEQ)/kg body weight in corn oil:acetone (99:1) by gavage, 5 days per week, for up to 105 weeks; a group of 81 vehicle control female rats received the corn oil/acetone vehicle alone. Actual doses used for each compound in the mixture were: for 10 ng TEQ/kg: 3.3 ng/kg TCDD, 6.6 ng/kg PeCDF, and 33.3 ng/kg PCB 126; for 22 ng TEQ/kg: 7.3 ng/kg TCDD, 14.5 ng/kg PeCDF, and 73.3 ng/kg PCB 126; for 46 ng TEQ/kg: 15.2 ng/kg TCDD, 30.4 ng/kg PeCDF, and 153 ng/kg PCB 126; and for 100 ng TEQ/kg: 33 ng/kg TCDD, 66 ng/kg PeCDF, and 333 ng/kg PCB 126. Up to 10 rats per group were evaluated at 14, 31, or 53 weeks. Survival of all dosed groups of rats was similar to that of the vehicle control group. Mean body weights of the 22 and 46 ng TEQ/kg groups were less than those of the vehicle control groups after week 69 of the study. Mean body weights of the 100 ng TEQ/kg group were less than those of the vehicle control group after week 37 of the study. Thyroid Hormone Concentrations: Alterations in serum thyroid hormone concentrations were evaluated at the 14-, 31-, and 53-week interim evaluations. At 14, 31, and 53 weeks, there were dose-dependent reductions in total serum and free thyroxine concentrations. There were dose-dependent increases in serum triiodothyronine concentrations at 14 and 31 weeks. No changes in serum thyroid stimulating hormone concentrations were observed at any time point. Hepatic Cell Proliferation Data: To evaluate hepatocyte replication, analysis of labeling of replicating hepatocytes with 5-bromo-2'-deoxyuridine was conducted at the interim evaluations. At 14 weeks, no effects on the hepatocellular labeling index were observed in the dosed groups compared to the vehicle controls. At 31 and 53 weeks, the hepatocellular labeling index was significantly higher in the 46 and 100 ng TEQ/kg groups compared to the vehicle controls. Cytochrome P450 Enzyme Activities: To evaluate the expression of known dioxin-responsive genes, CYP1A1 associated 7-ethoxyresorufin-O-deethylase (EROD) activity and CYP1A2-associated acetanilide-4-hydroxylase (A4H) activity were evaluated at the interim time points. Liver and lung EROD (CYP1A1) activities and hepatic A4H (CYP1A2) activities were significantly greater in all dosed groups than in the vehicle controls at all interim evaluations (14, 31, and 53 weeks). Determinations of TCDD, PeCDF, and PCB 126 Concentrations in Tissues: Tissue concentrations of TCDD, PeCDF, and PCB 126 were analyzed in the fat, liver, lung, and blood at each interim evaluation and at the end of the 2-year study (105 weeks). The highest concentrations of TCDD, PeCDF, and PCB 126 were observed in the liver followed by fat. Liver and fat concentrations of TCDD, PeCDF, and PCB 126 at each interim evaluation and at 105 weeks were higher in groups with increasing doses of the mixture and generally increased with duration of dosing. In the lung, PeCDF was present at detectable concentrations in the 46 and 100 ng TEQ/kg groups at 14 and 31 weeks. Measurable concentrations of TCDD and PCB 126 were observed at 14 and 31 weeks in the lung of rats in all dosed groups with the highest concentrations observed in the 100 ng TEQ/kg group. At 53 weeks, concentrations of TCDD, PeCDF, and PCB 126 in the lung generally increased with increasing dose. At 105 weeks, detectable concentrations of TCDD, PeCDF, and PCB 126 in the lung were observed in all dosed groups. In blood, TCDD and PCB 126 concentrations at 14 and 31 weeks generally increased with increasing dose. Blood concentrations of PeCDF were detectable in the 46 and 100 ng TEQ/kg groups at 14 weeks and at 22 ng TEQ/kg or greater at 31 weeks. At 53 and 105 weeks, concentrations of TCDD, PeCDF, and PCB 126 in blood generally increased with increasing dose and duration of dosing. Pathology and Statistical Analyses: Relative liver weights were significantly increased in all dosed groups at 14, 31, and 53 weeks and correlated with increased incidences of hepatocellular hypertrophy. Increasing duration of exposure led to an increase in the spectrum, incidence, and severity of nonneoplastic effects. The only significant effect at 14 weeks was increased incidences of hepatocellular hypertrophy. At 53 weeks, there was a significant effect on the incidences of hepatocellular hypertrophy, multinucleated hepatocytes, pigmentation, focal fatty change, bile duct hyperplasia, and toxic hepatopathy. At 2 years, there were significant increases in the incidences of hepatocellular adenoma and cholangiocarcinoma of the liver. There was an increase in hepatic toxicity characterized by increases in the incidences of numerous nonneoplastic lesions including hepatocyte hypertrophy, multinucleated hepatocytes, pigmentation, inflammation, diffuse fatty change, bile duct hyperplasia, oval cell hyperplasia, nodular hyperplasia, eosinophilic focus, cholangiofibrosis, bile duct cysts, necrosis, portal fibrosis, mixed cell focus, and toxic hepatopathy. In the lung, there were dose-dependent increases in the incidences of bronchiolar metaplasia of the alveolar epithelium at 53 weeks and at 2 years and squamous metaplasia at 2 years. At 2 years, there was a dose dependent increase in the incidences of cystic keratinizing epithelioma. In the pancreas, there were increases in the incidences of numerous nonneoplastic lesions including arterial chronic active inflammation, acinar cytoplasmic vacuolization, acinar atrophy, chronic active inflammation, and duct dilatation. At 2 years, incidences of acinar adenoma or acinar carcinoma that exceeded the historical control ranges were seen in all dosed groups except the 100 ng TEQ/kg group. Treatment-related increases in the incidences of nonneoplastic lesions were seen in other organs including hyperplasia, cystic degeneration, atrophy, and cytoplasmic vacuolization of the adrenal cortex; gingival squamous hyperplasia of the oral mucosa; squamous metaplasia of the uterus; atrophy of the thymus (incidence and severity); chronic active inflammation of the ovary; nephropathy of the kidney (incidence and severity); cardiomyopathy; bone marrow hyperplasia; transitional epithelium of the urinary bladder; chronic active inflammation of the mesenteric artery; and follicular cell hypertrophy of the thyroid gland. (ABSTRACT TRUNCATED). PMID- 17342196 TI - Toxicology and carcinogenesis studies of a binary mixture of 3,3',4,4',5 pentachlorobiphenyl (PCB 126) (Cas No. 57465-28-8) and 2,3',4,4',5 pentachlorobiphenyl (PCB 118) (Cas No. 31508-00-6) in female Harlan Sprague Dawley rats (gavage studies). AB - DIOXIN TOXIC EQUIVALENCY FACTOR EVALUATION OVERVIEW: Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds" (DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized they accumulate in body tissue, mainly adipose, resulting in chronic lifetime human exposure. Since human exposure to DLCs always occurs as a complex mixture, the toxic equivalency factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally related polychlorinated biphenyls (PCBs) and mixtures of these compounds. Mixtures of polychlorinated biphenyls (PCBs) including 3,3',4,4',5-pentachlorobiphenyl (PCB 126) and 2,3',4,4',5 pentachlorobiphenyl (PCB 118) were produced commercially before 1977 for the electric industry as dielectric insulating fluids for transformers and capacitors. Manufacture and use of these chemicals were stopped because of increased PCB residues in the environment, but they continue to be released into the environment through the use and disposal of products containing PCBs, as by products during the manufacture of certain organic chemicals, during combustion of some waste materials, and during atmospheric recycling. This PCB mixture study was conducted as part of the dioxin TEF evaluation that includes conducting multiple 2-year rat bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLCs, structurally related PCBs, and mixtures of these compounds. This study was originally a study of PCB 118 alone. However, midway through the study PCB 126 was identified as one of the minor contaminants (0.622%) of the bulk PCB 118 (98.5% pure). Given the 1,000-fold higher potency of PCB 126 for inducing dioxin-like effects (based on the TEFs for PCB 126 and PCB 118 of 0.1 and 0.0001, respectively), it was expected that the effects of administration of this compound would be due to the combined dioxin-like effects of both PCB 126 and PCB 118. Therefore, this study was reclassified as a mixture study of PCB 126 and PCB 118. 2-YEAR STUDY: Groups of female Harlan Sprague Dawley rats were administered the PCB mixture containing PCB 126 and PCB 118 by gavage in corn oil:acetone (99:1) or vehicle alone, 5 days per week for up to 104 weeks. Dose groups are referred to by the total levels of TCDD toxic equivalents (TEQ) provided by the PCBs in the mixture in each dose group. Groups of 81 female rats were administered 7, 22, 72, or 216 ng TEQ/kg; a group of 86 female rats was administered 360 ng TEQ/kg; and a group of 81 female rats was administered the corn oil:acetone vehicle alone. Up to 10 rats per group were evaluated at 14, 31, or 53 weeks. No animals in the 360 ng TEQ/kg group were examined at 53 weeks. A group of 50 female rats was administered 360 ng TEQ/kg for 30 weeks and then the vehicle alone for the remainder of the study. Nominal doses of PCB 118 and levels of PCB 126 in each dose group used were: 7 ng TEQ/kg dose group: 62 ng/kg PCB 126 and 10 microg/kg PCB 118 7 ng TEQ/kg dose group: 62 ng/kg PCB 126 and 10 microg/kg PCB 118 22 ng TEQ/kg dose group: 187 ng/kg PCB 126 and 30 microg/kg PCB 118 72 ng TEQ/kg dose group: 622 ng/kg PCB 126 and 100 microg/kg PCB 118 216 ng TEQ/kg dose group: 1,866 ng/kg PCB 126 and 300 microg/kg PCB 118 360 ng TEQ/kg dose group: 3,110 ng/kg PCB 126 and 500 microg/kg PCB 118 No animals in the 216 or 360 ng TEQ/kg core study groups survived to the end of the study, and survival in the 360 ng TEQ/kg stop-exposure group was significantly less than in the vehicle control group. Mean body weights of 72 ng TEQ/kg rats were less than those of the vehicle controls after week 33 of the study, and mean body weights of the 216 and 360 ng TEQ/kg core study rats and the 360 ng TEQ/kg stop-exposure group rats were less than those of the vehicle controls throughout most of the study. Clinical findings related to the administration of the binary mixture of PCB 126 and PCB 118 included abnormal breathing, thinness, and ruffled hair. Thyroid Hormone Concentrations: Alterations in serum thyroid hormone levels were evaluated at the 14-, 31-, and 53-week interim evaluations. Total thyroxine (T4) and free T4 were significantly lower in most dose groups than in vehicle controls at the 14- and 31-week interim evaluations. Serum T3 was significantly lower in the 360 ng TEQ/kg group compared to vehicle controls at 31 weeks only. TSH levels were higher in the 216 and 360 ng TEQ/kg groups than in vehicle controls at 31 weeks only. Hepatic Cell Proliferation Data To evaluate hepatocyte replication, analysis of labeling of replicating hepatocytes with 5-bromo-2'-deoxyuridine was conducted at the 14-, 31-, and 53-week interim evaluations. Labeling indices were elevated at doses above 216 ng TEQ/kg at 31 weeks and at doses above 72 ng TEQ/kg at 53 weeks. Cytochrome P450 Enzyme Activities: CYP1A1-associated 7 ethoxyresorufin-O-deethylase (EROD) and CYP1A2-associated acetanilide-4 hydroxylase (A4H) activities were evaluated at the 14-, 31-, and 53-week interim evaluations to evaluate the expression of known dioxin-responsive genes. In addition, CYP2B-associated pentoxyresorufin-O-deethylase (PROD) activity was also analyzed. Hepatic and pulmonary EROD (CYP1A1) activity, hepatic A4H (CYP1A2) activity, and hepatic PROD (CYP2B1) activity were significantly greater in all dosed groups compared to the vehicle controls at weeks 14, 31, and 53. Determinations of PCB 126 and PCB 118 Concentrations in Tissues: The tissue disposition of PCB 126 and PCB 118 was analyzed in the liver, lung, fat, and blood of up to 10 rats in each group at the 14-, 31-, and 53-week interim evaluations, except for the 360 ng TEQ/kg group at 53 weeks. The tissue disposition of PCB 126 and PCB 118 was also analyzed in 10 rats per group at the end of the 2-year study in the vehicle control, 7, 22, and 72 ng TEQ/kg core study groups and the 360 ng TEQ/kg stop-exposure group. Detectable concentrations of PCB 126 and PCB 118 were observed in the liver, fat, lung, and blood. The highest levels of PCB 126 were seen in the liver whereas the highest levels of PCB 118 were seen in the fat. In general, tissue concentrations increased with increasing doses of the mixture and increasing duration of exposure. Hepatic levels of PCB 126 and PCB 118 in the 72 ng TEQ/kg group at the end of the 2-year study were 284 ng/g and 3,769 ng/g, respectively. On a TCDD equivalents basis this corresponds to 28 ng TEQ/g and 0.4 ng TEQ/g for PCB 126 and PCB 118, respectively. Cessation of administration of the mixture in the stop-exposure group led to declines in the tissue concentrations of both PCB 126 and PCB 118 to levels comparable to those observed in the 7 ng TEQ/kg group at the end of the 2 year study. Pathology and Statistical Analyses: At 14, 31, and 53 weeks, liver weights were significantly increased in treated groups with more pronounced effects occurring in the higher dose groups. At 14 weeks, hepatocyte hypertrophy and pigmentation were seen at doses less than 72 ng TEQ/kg. Exposure to the PCB mixture led to significant toxicity in the liver. At higher doses, the incidences of toxic hepatopathy were increased as indicated by increased incidences of multinucleated hepatocytes and diffuse fatty change. At 31 weeks, most rats in the 216 and 360 ng TEQ/kg groups had multiple hepatic nonneoplastic lesions. At 53 weeks all animals administered 216 ng TEQ/kg had multiple nonneoplastic lesions. The spectrum of effects and the severity of effects at the interim and 2 year time points increased with dose and duration of exposure. At the end of the 2-year study in all dosed groups, there were significantly increased incidences and severity of toxic hepatopathy characterized by hepatocyte hypertrophy, multinucleated hepatocytes, pigmentation, toxic hepatopathy, diffuse fatty change, nodular hyperplasia, centrilobular fibrosis, cholangiofibrosis, oval cell hyperplasia, bile duct cyst, bile duct hyperplasia, and portal fibrosis. There were also increased incidences of hepatocyte glandular structures, necrosis, centrilobular degeneration, eosinophilic focus, and metaplasia. The incidences of cholangiocarcinoma (multiple and/or single) were significantly increased in groups administered 22 ng TEQ/kg or greater at 2 years. The incidences of hepatocellular adenoma were also significantly increased in the 216 and 360 ng TEQ/kg core study groups. In addition, single occurrences of hepatocholangioma, cholangioma, or hepatocellular carcinoma were observed in some dosed groups administered 72 ng TEQ/kg or greater. In the lung at 53 weeks, the incidences of cystic keratinizing epithelioma and bronchiolar metaplasia were significantly increased in the 216 ng TEQ/kg group. (ABSTRACT TRUNCATED). PMID- 17342197 TI - Toxicology and carcinogenesis studies of divinylbenzene-HP (Cas No. 1321-74-0) in F344/N rats and B6C3F1 mice (inhalation studies). AB - Divinylbenzene-HP is used for producing vinyl polymers. Divinylbenzene-HP was nominated for study by the National Cancer Institute because of the potential for worker exposure and the structural similarity of divinylbenzene to styrene, a potential human carcinogen. Male and female F344/N rats and B6C3F1 mice were exposed to divinylbenzene-HP (80%) by inhalation for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were exposed by whole body inhalation to divinylbenzene-HP at target concentrations of 0, 25, 50, 100, 200, or 400 ppm 6 hours plus T90 (12 minutes) per day, 5 days per week for 16 days. All rats survived to the end of the study. Significant decreases in mean body weights occurred in both male and female rats in the 400 ppm groups. Relative kidney weights of 50 ppm or greater males and relative liver weights of 200 and 400 ppm males were significantly greater than those of the chamber controls. A clear serous nasal/eye discharge was observed in groups of males exposed to 100 ppm or greater and females exposed to 50 ppm or greater. Minimal or mild rhinitis occurred in 400 ppm rats of both sexes. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were exposed by whole body inhalation to divinylbenzene-HP at target concentrations of 0, 25, 50, 100, 200, or 400 ppm for 6 hours plus T90 (12 minutes) per day, 5 days per week for 17 days. All 400 ppm males and females died on or before the second day of the study, and two male and two female 200 ppm mice died early. Mean body weights of 100 and 200 ppm males were significantly less than those of the chamber controls. Thymus weights of exposed groups of males were significantly less than those of the chamber controls, and relative liver weights of 100 and 200 ppm males were significantly increased. Kidney and liver weights of exposed groups of females were significantly greater than those of the chamber controls. Mice exposed to 200 and 400 ppm had liver lesions including degeneration, necrosis, hemorrhage or cytomegaly. Renal tubule necrosis and regeneration occurred at 200 ppm. Necrosis or metaplasia of nasal epithelium and glands occurred in the nose in all exposure groups. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to divinylbenzene-HP at concentrations of 0, 25, 50, 100, 200, or 400 ppm for 6 hours plus T90 (12 minutes) per day, 5 days per week for 14 weeks. All rats survived to the end of the study. There were no biologically significant changes in body weight in either sex. Nasal/eye discharge was noted in 400 ppm males and 100 ppm females. Kidney and liver weights of exposed groups of males and of 400 ppm females were generally greater than those of the chamber controls. In addition, the relative weights of the heart and testis were significantly increased in 200 and 400 ppm males. Incidences of degeneration of the olfactory epithelium in 200 and 400 ppm rats and basal cell hyperplasia of the olfactory epithelium in rats exposed to 100 ppm or greater were significantly increased. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to divinylbenzene-HP at concentrations of 0, 12.5, 25, 50, 100, or 200 ppm for 6 hours plus T90 (12 minutes) per day, 5 days per week for 14 weeks. All 200 ppm males and nine 200 ppm females died early. Final mean body weights were significantly lower in males and females exposed to 25, 50, or 100 ppm when compared with chamber controls. Lethargy or hypoactivity was observed in the higher exposure concentration groups. Exposure to divinylbenzene was associated with necrosis of the liver and kidney in 200 ppm males and females dying early. In all exposed groups of male and female mice, there was necrosis of nasal cavity lateral walls, olfactory epithelium, and glands with resultant atrophy of olfactory epithelium and glands in females. A lower number of animals had necrotic or degenerative changes of the upper respiratory tract. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to divinylbenzene-HP at concentrations of 0, 100, 200, or 400 ppm for 6 hours plus T90 (12 minutes) per day, 5 days per week for up to 105 weeks. Survival of 400 ppm females was significantly less than that of the chamber control group. Survival of all exposed groups of males was similar to that of the chamber control group. Mean body weights of 400 ppm males and females were significantly less than those of the controls during the second half of the study. Renal tubule carcinomas occurred in two of 50 males exposed to 400 ppm in the original kidney sections, an incidence that exceeded the historical control range. In 400 ppm males, the incidence of renal tubule hyperplasia was increased, and the incidence of nephropathy was significantly increased. Following combined analysis of single and step-section data, the incidences of renal tubule adenoma and adenoma or carcinoma (combined) were marginally higher in 200 and 400 ppm males, and the incidence of renal tubule hyperplasia was significantly increased in 400 ppm males. The incidences of malignant glial cell tumors (malignant astrocytoma and oligodendroglioma) in the brain were slightly increased in 100 and 200 ppm males, and the incidence in the 200 ppm group exceeded the historical range for chamber controls. There were increased incidences of degenerative and regenerative changes in the olfactory epithelium in the nose of all exposed groups of rats. The incidence of focal chronic inflammation in the lung of 400 ppm males was significantly greater than in the chamber control group. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to divinylbenzene-HP at concentrations of 0, 10, 30, or 100 ppm for 6 hours plus T90 (12 minutes) per day, 5 days per week for up to 105 weeks. Survival of all exposed groups of male and female mice was similar to that of the chamber controls. Mean body weights were lower relative to chamber controls in 100 ppm males and in 30 and 100 ppm females. The incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined) in 100 ppm males were greater than chamber control incidences, but the incidences of adenoma or carcinoma (combined) were within the historical control range. The incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined) in all exposed groups of females were generally greater than those of the chamber controls; the incidences were at the upper end or exceeded the historical control ranges. There was a greater incidence and severity of alveolar epithelial hyperplasia in 100 ppm females and a greater severity of this lesion in 30 ppm females, when compared to chamber controls. The incidences and/or severities of atypical bronchiole hyperplasia were significantly increased in all exposed groups of mice. Nonneoplastic nasal lesions occurred in most exposed mice. GENETIC TOXICOLOGY: Divinylbenzene-HP was not mutagenic in any of three independent gene mutation assays using Salmonella typhimurium strains TA97, TA98, TA100, TA1535, or TA1537 or Escherichia coli tester strain WP2 uvrA with or without induced hamster or rat liver enzymes. No increases in the frequencies of micronucleated normochromatic erythrocytes or alterations in the percentages of polychromatic erythrocytes were seen in peripheral blood of male or female B6C3F1 mice exposed to divinylbenzene-HP by inhalation for 3 months. CONCLUSIONS: Under the conditions of this 2-year inhalation study, there was equivocal evidence of carcinogenic activity of divinylbenzene-HP in male F344/N rats based upon the occurrence of carcinomas in the kidney and glial tumors in the brain. There was no evidence of carcinogenic activity in female F344/N rats exposed to 100, 200, or 400 ppm divinylbenzene-HP. There was no evidence of carcinogenic activity in male B6C3F1 mice exposed to 10, 30, or 100 ppm divinylbenzene-HP. There was equivocal evidence of carcinogenic activity of divinylbenzene-HP in female B6C3F1 mice based on the incidences of alveolar/bronchiolar adenoma or carcinoma (combined) in the lung. Exposure to divinylbenzene-HP caused nonneoplastic lesions of the nasal cavity in male and female rats and of the lung and nasal cavity in male and female mice. PMID- 17342198 TI - Toxicology and carcinogenesis studies of 4-methylimidazole (Cas No. 822-36-6) in F344/N rats and B6C3F1 mice (feed studies). AB - 4-Methylimidazole is used in the manufacture of pharmaceuticals, photographic chemicals, dyes and pigments, cleaning and agricultural chemicals, and rubber. It has been identified as a by-product of fermentation in foods and has been detected in mainstream and sidestream tobacco smoke. 4-Methylimidazole was nominated by the National Cancer Institute for a long-term study because of the high potential for human exposure. Male and female F344/N rats and B6C3F1 mice were exposed to 4-methylimidazole (99.5% pure) in feed for 2 years. Fifteen-day and 14-week toxicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice are reported in NTP Toxicity Report No. 67. Genetic toxicology studies were conducted in Salmonella typhimurium, rat and mouse bone marrow cells, and mouse peripheral blood. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were fed diets containing 0, 625, 1,250, or 2,500 ppm 4-methylimidazole (males) or 0, 1,250, 2,500, or 5,000 ppm 4-methylimidazole (females) (equivalent to average daily doses of approximately 30, 55, or 115 mg 4-methylimidazole/kg body weight to males and 60, 120, or 260 mg/kg to females) for 106 weeks. Survival of all exposed groups of male and female rats was similar to that of the control groups. Mean body weights of males in the 1,250 and 2,500 ppm groups and females in the 2,500 and 5,000 ppm groups were less than those of the control groups throughout the study; mean body weights of 1,250 ppm females were less after week 41. Feed consumption by 5,000 ppm females was less than that by the controls. Clonic seizures, excitability, hyperactivity, and impaired gait were observed primarily in 2,500 and 5,000 ppm females. The incidence of mononuclear cell leukemia in 5,000 ppm females was significantly greater than that in the controls, and the incidence exceeded the historical range in feed study controls. The incidences of hepatic histiocytosis, chronic inflammation, and focal fatty change were generally significantly increased in all exposed groups of male and female rats. The incidences of hepatocellular eosinophilic and mixed cell focus were significantly increased in 2,500 ppm males and 5,000 ppm females. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were fed diets containing 0, 312, 625, or 1,250 ppm 4-methylimidazole (equivalent to average daily doses of approximately 40, 80, and 170 mg 4-methylimidazole/kg body weight to males and females) for 106 weeks. Survival of all exposed groups of male and female mice was similar to that of the control groups. Mean body weights of males and females in the 1,250 ppm groups were less than those of the control groups after weeks 17 and 12, respectively. Mean body weights of 312 and 625 ppm females were less after weeks 85 and 65, respectively. Feed consumption by exposed groups of male and female mice was generally similar to that by the controls. The incidences of alveolar/bronchiolar adenoma in all exposed groups of females, alveolar/bronchiolar carcinoma in 1,250 ppm males, and alveolar/bronchiolar adenoma or carcinoma (combined) in 1,250 ppm males and 625 and 1,250 ppm females were significantly greater than those in the control groups. The incidence of alveolar epithelium hyperplasia was significantly increased in 1,250 ppm females. GENETIC TOXICOLOGY: 4-Methylimidazole was not mutagenic in the S. typhimurium mutation assay when tested in strains TA97, TA98, TA100, and TA1535, with and without hamster or rat liver metabolic activation enzymes. No consistent or significant increases in the frequencies of micronucleated erythrocytes were seen in the bone marrow of male rats or mice treated with 4-methylimidazole by intraperitoneal injection, or in peripheral blood samples from male and female mice administered the compound in dosed feed for 14 weeks. CONCLUSIONS: Under the conditions of these 2-year studies, there was no evidence of carcinogenic activity of 4-methylimidazole in male F344/N rats exposed to 625, 1,250, or 2,500 ppm. There was equivocal evidence of carcinogenic activity of 4-methylimidazole in female F344/N rats based on increased incidences of mononuclear cell leukemia. There was clear evidence of carcinogenic activity of 4-methylimidazole in male and female B6C3F1 mice based on increased incidences of alveolar/bronchiolar neoplasms. Exposure to 4-methylimidazole resulted in nonneoplastic lesions in the liver of male and female rats and the lung of female mice and in clinical findings of neurotoxicity in female rats. PMID- 17342199 TI - Major flame burn caused by electric fly-swatter. PMID- 17342200 TI - Plasmids and rickettsial evolution: insight from Rickettsia felis. AB - BACKGROUND: The genome sequence of Rickettsia felis revealed a number of rickettsial genetic anomalies that likely contribute not only to a large genome size relative to other rickettsiae, but also to phenotypic oddities that have confounded the categorization of R. felis as either typhus group (TG) or spotted fever group (SFG) rickettsiae. Most intriguing was the first report from rickettsiae of a conjugative plasmid (pRF) that contains 68 putative open reading frames, several of which are predicted to encode proteins with high similarity to conjugative machinery in other plasmid-containing bacteria. METHODOLOGY/PRINCIPAL FINDINGS: Using phylogeny estimation, we determined the mode of inheritance of pRF genes relative to conserved rickettsial chromosomal genes. Phylogenies of chromosomal genes were in agreement with other published rickettsial trees. However, phylogenies including pRF genes yielded different topologies and suggest a close relationship between pRF and ancestral group (AG) rickettsiae, including the recently completed genome of R. bellii str. RML369-C. This relatedness is further supported by the distribution of pRF genes across other rickettsiae, as 10 pRF genes (or inactive derivatives) also occur in AG (but not SFG) rickettsiae, with five of these genes characteristic of typical plasmids. Detailed characterization of pRF genes resulted in two novel findings: the identification of oriV and replication termination regions, and the likelihood that a second proposed plasmid, pRFdelta, is an artifact of the original genome assembly. CONCLUSION/SIGNIFICANCE: Altogether, we propose a new rickettsial classification scheme with the addition of a fourth lineage, transitional group (TRG) rickettsiae, that is unique from TG and SFG rickettsiae and harbors genes from possible exchanges with AG rickettsiae via conjugation. We offer insight into the evolution of a plastic plasmid system in rickettsiae, including the role plasmids may have played in the acquirement of virulence traits in pathogenic strains, and the likely origin of plasmids within the rickettsial tree. PMID- 17342201 TI - Selective alpha-particle mediated depletion of tumor vasculature with vascular normalization. AB - BACKGROUND: Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature. METHODOLOGY AND PRINCIPAL FINDINGS: Actinium-225 ((225)Ac)-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225)Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225)Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225)Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225)Ac-E4G10 therapy. CONCLUSIONS: The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy. PMID- 17342202 TI - Tagging single nucleotide polymorphisms in the BRIP1 gene and susceptibility to breast and ovarian cancer. AB - BACKGROUND: BRIP1 interacts with BRCA1 and functions in regulating DNA double strand break repair pathways. Germline BRIP1 mutations are associated with breast cancer and Fanconi anemia. Thus, common variants in the BRIP1 are candidates for breast and ovarian cancer susceptibility. METHODS: We used a SNP tagging approach to evaluate the association between common variants (minor allele frequency>or=0.05) in BRIP1 and the risks of breast cancer and invasive ovarian cancer. 12 tagging SNPs (tSNPs) in the gene were identified and genotyped in up to 2,270 breast cancer cases and 2,280 controls from the UK and up to 1,513 invasive ovarian cancer cases and 2,515 controls from the UK, Denmark and USA. Genotype frequencies in cases and controls were compared using logistic regression. RESULTS: Two tSNPs showed a marginal significant association with ovarian cancer: Carriers of the minor allele of rs2191249 were at reduced risk compared with the common homozygotes (Odds Ratio (OR) = 0.90 (95% CI, 0.82-1.0), P-trend = 0.045) and the minor allele of rs4988344 was associated with increased risk (OR = 1.15 (95%CI, 1.02-1.30), P-trend = 0.02). When the analyses were restricted to serous ovarian cancers, these effects became slightly stronger. These results were not significant at the 5% level after adjusting for multiple testing. None of the tSNPs was associated with breast cancer. CONCLUSIONS: It is unlikely that common variants in BRIP1 contribute significantly to breast cancer susceptibility. The possible association of rs2191249 and rs4988344 with ovarian cancer risks warrant confirmation in independent case-control studies. PMID- 17342203 TI - Ligand bound beta1 integrins inhibit procaspase-8 for mediating cell adhesion mediated drug and radiation resistance in human leukemia cells. AB - BACKGROUND: Chemo- and radiotherapeutic responses of leukemia cells are modified by integrin-mediated adhesion to extracellular matrix. To further characterize the molecular mechanisms by which beta1 integrins confer radiation and chemoresistance, HL60 human acute promyelocytic leukemia cells stably transfected with beta1 integrin and A3 Jurkat T-lymphoma cells deficient for Fas-associated death domain protein or procaspase-8 were examined. METHODOLOGY/PRINCIPAL FINDINGS: Upon exposure to X-rays, Ara-C or FasL, suspension and adhesion (fibronectin (FN), laminin, collagen-1; 5-100 microg/cm(2) coating concentration) cultures were processed for measurement of apoptosis, mitochondrial transmembrane potential (MTP), caspase activation, and protein analysis. Overexpression of beta1 integrins enhanced the cellular sensitivity to X-rays and Ara-C, which was counteracted by increasing concentrations of matrix proteins in association with reduced caspase-3 and -8 activation and MTP breakdown. Usage of stimulatory or inhibitory anti beta1 integrin antibodies, pharmacological caspase or phosphatidylinositol-3 kinase (PI3K) inhibitors, coprecipitation experiments and siRNA-mediated beta1 integrin silencing provided further data showing an interaction between FN-ligated beta1 integrin and PI3K/Akt for inhibiting procaspase-8 cleavage. CONCLUSIONS/SIGNIFICANCE: The presented data suggest that the ligand status of beta1 integrins is critical for their antiapoptotic effect in leukemia cells treated with Ara-C, FasL or ionizing radiation. The antiapoptotic actions involve formation of a beta1 integrin/Akt complex, which signals to prevent procaspase-8-mediated induction of apoptosis in a PI3K dependent manner. Antagonizing agents targeting beta1 integrin and PI3K/Akt signaling in conjunction with conventional therapies might effectively reduce radiation- and drug-resistant tumor populations and treatment failure in hematological malignancies. PMID- 17342204 TI - Chromodynamics of cooperation in finite populations. AB - BACKGROUND: The basic idea of tag-based models for cooperation is that individuals recognize each other via arbitrary signals, so-called tags. If there are tags of different colors, then cooperators can always establish new signals of recognition. The resulting "chromodynamics" is a mechanism for the evolution of cooperation. Cooperators use a secret tag until they are discovered by defectors who then destroy cooperation based on this tag. Subsequently, a fraction of the population manages to establish cooperation based on a new tag. METHODOLOGY/PRINCIPAL FINDINGS: We derive a mathematical description of stochastic evolutionary dynamics of tag-based cooperation in populations of finite size. Benefit and cost of cooperation are given by b and c. We find that cooperators are more abundant than defectors if b/c > 1+2u/v, where u is the mutation rate changing only the strategy and v is the mutation rate changing strategy and tag. We study specific assumptions for u and v in two genetic models and one cultural model. CONCLUSIONS/SIGNIFICANCE: In a genetic model, tag-based cooperation only evolves if a gene encodes both strategy and tag. In a cultural model with equal mutation rates between all possible phenotypes (tags and behaviors), the crucial condition is b/c > (K+1)/(K-1), where K is the number of tags. A larger number of tags requires a smaller benefit-to-cost ratio. In the limit of many different tags, the condition for cooperators to have a higher average abundance than defectors becomes b > c. PMID- 17342206 TI - DNA extraction from dry museum beetles without conferring external morphological damage. AB - BACKGROUND: A large number of dry-preserved insect specimens exist in collections around the world that might be useful for genetic analyses. However, until now, the recovery of nucleic acids from such specimens has involved at least the partial destruction of the specimen. This is clearly undesirable when dealing with rare species or otherwise important specimens, such as type specimens. METHODOLOGY: We describe a method for the extraction of PCR-amplifiable mitochondrial and nuclear DNA from dry insects without causing external morphological damage. Using PCR to amplify approximately 220 bp of the mitochondrial gene cytochrome c oxidase I, and 250-345 bp fragments of the multi copy, nuclear 28s ribosomal DNA gene, we demonstrate the efficacy of this method on beetles collected up to 50 years ago. CONCLUSIONS: This method offers a means of obtaining useful genetic information from rare insects without conferring external morphological damage. PMID- 17342205 TI - Adaptation of HIV-1 depends on the host-cell environment. AB - Many viruses have the ability to rapidly develop resistance against antiviral drugs and escape from the host immune system. To which extent the host environment affects this adaptive potential of viruses is largely unknown. Here we show that for HIV-1, the host-cell environment is key to the adaptive potential of the virus. We performed a large-scale selection experiment with two HIV-1 strains in two different T-cell lines (MT4 and C8166). Over 110 days of culture, both virus strains adapted rapidly to the MT4 T-cell line. In contrast, when cultured on the C8166 T-cell line, the same strains did not show any increase in fitness. By sequence analyses and infections with viruses expressing either yellow or cyan fluorescent protein, we were able to show that the absence of adaptation was linked to a lower recombination rate in the C8166 T-cell line. Our findings suggest that if we can manipulate the host-cellular factors that mediate viral evolution, we may be able to significantly retard viral adaptability. PMID- 17342207 TI - An assessment of the role of DNA adenine methyltransferase on gene expression regulation in E coli. AB - N6-Adenine methylation is an important epigenetic signal, which regulates various processes, such as DNA replication and repair and transcription. In gamma proteobacteria, Dam is a stand-alone enzyme that methylates GATC sites, which are non-randomly distributed in the genome. Some of these overlap with transcription factor binding sites. This work describes a global computational analysis of a published Dam knockout microarray alongside other publicly available data to throw insights into the extent to which Dam regulates transcription by interfering with protein binding. The results indicate that DNA methylation by DAM may not globally affect gene transcription by physically blocking access of transcription factors to binding sites. Down-regulation of Dam during stationary phase correlates with the activity of TFs whose binding sites are enriched for GATC sites. PMID- 17342208 TI - Evolution of Anolis lizard dewlap diversity. AB - BACKGROUND: The dewlaps of Anolis lizards provide a classic example of a complex signaling system whose function and evolution is poorly understood. Dewlaps are flaps of skin beneath the chin that are extended and combined with head and body movements for visual signals and displays. They exhibit extensive morphological variation and are one of two cladistic features uniting anoles, yet little is known regarding their function and evolution. We quantified the diversity of anole dewlaps, investigated whether dewlap morphology was informative regarding phylogenetic relationships, and tested two separate hypotheses: (A) similar Anolis habitat specialists possess similar dewlap configurations (Ecomorph Convergence hypothesis), and (B) sympatric species differ in their dewlap morphologies to a greater extent than expected by chance (Species Recognition hypothesis). METHODOLOGY/PRINCIPAL FINDINGS: We found that dewlap configurations (sizes, patterns and colors) exhibit substantial diversity, but that most are easily categorized into six patterns that incorporate one to three of 13 recognizable colors. Dewlap morphology is not phylogenetically informative and, like other features of anoles, exhibits convergence in configurations. We found no support for the Ecomorph Convergence hypothesis; species using the same structural habitat were no more similar in dewlap configuration than expected by chance. With one exception, all sympatric species in four communities differ in dewlap configuration. However, this provides only weak support for the Species Recognition hypothesis because, due to the great diversity in dewlap configurations observed across each island, few cases of sympatric species with identical dewlaps would be expected to co-occur by chance alone. CONCLUSIONS/SIGNIFICANCE: Despite previous thought, most dewlaps exhibit easily characterizable patterns and colorations. Nevertheless, dewlap variation is extensive and explanations for the origin and evolution of this diversity are lacking. Our data do not support two hypothesized explanations for this diversity, but others such as sexual selection remain to be tested. PMID- 17342209 TI - In vivo bioluminescence imaging of Ca signalling in the brain of Drosophila. AB - Many different cells' signalling pathways are universally regulated by Ca(2+) concentration [Ca(2+)] rises that have highly variable amplitudes and kinetic properties. Optical imaging can provide the means to characterise both the temporal and spatial aspects of Ca(2+) signals involved in neurophysiological functions. New methods for in vivo imaging of Ca(2+) signalling in the brain of Drosophila are required for probing the different dynamic aspects of this system. In studies here, whole brain Ca(2+) imaging was performed on transgenic flies with targeted expression of the bioluminescent Ca(2+) reporter GFP-aequorin (GA) in different neural structures. A photon counting based technique was used to undertake continuous recordings of cytosolic [Ca(2+)] over hours. Time integrals for reconstructing images and analysis of the data were selected offline according to the signal intensity. This approach allowed a unique Ca(2+) response associated with cholinergic transmission to be identified by whole brain imaging of specific neural structures. Notably, [Ca(2+)] transients in the Mushroom Bodies (MBs) following nicotine stimulation were accompanied by a delayed secondary [Ca(2+)] rise (up to 15 min. later) in the MB lobes. The delayed response was sensitive to thapsigargin, suggesting a role for intra-cellular Ca(2+) stores. Moreover, it was reduced in dunce mutant flies, which are impaired in learning and memory. Bioluminescence imaging is therefore useful for studying Ca(2+) signalling pathways and for functional mapping of neurophysiological processes in the fly brain. PMID- 17342210 TI - TMS-induced cortical potentiation during wakefulness locally increases slow wave activity during sleep. AB - BACKGROUND: Sleep slow wave activity (SWA) is thought to reflect sleep need, increasing in proportion to the length of prior wakefulness and decreasing during sleep. However, the process responsible for SWA regulation is not known. We showed recently that SWA increases locally after a learning task involving a circumscribed brain region, suggesting that SWA may reflect plastic changes triggered by learning. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis directly, we used transcranial magnetic stimulation (TMS) in conjunction with high-density EEG in humans. We show that 5-Hz TMS applied to motor cortex induces a localized potentiation of TMS-evoked cortical EEG responses. We then show that, in the sleep episode following 5-Hz TMS, SWA increases markedly (+39.1+/-17.4%, p<0.01, n = 10). Electrode coregistration with magnetic resonance images localized the increase in SWA to the same premotor site as the maximum TMS induced potentiation during wakefulness. Moreover, the magnitude of potentiation during wakefulness predicts the local increase in SWA during sleep. CONCLUSIONS/SIGNIFICANCE: These results provide direct evidence for a link between plastic changes and the local regulation of sleep need. PMID- 17342212 TI - Physical illness in people with mental disorders. PMID- 17342211 TI - The WPA-WHO Joint Statement on the Role of Psychiatrists in Disasters Response. PMID- 17342213 TI - Mental health care for the elderly in low-income countries: a health systems approach. AB - Future development of services for older people needs to be tailored to suit the health systems context. Low-income countries lack the economic and human capital to contemplate widespread introduction of specialist services. The most cost effective way to manage people with dementia will be through supporting, educating and advising family caregivers. The next level of care to be prioritized would be respite care, both in day centres and in residential or nursing homes. An important prerequisite to improving care for older persons is to create a climate that fosters such advances. Better awareness is a necessary precondition for appropriate help-seeking, and lack of awareness is a public health problem for which population level interventions are needed. PMID- 17342214 TI - A review of compulsive buying disorder. AB - Compulsive buying disorder (CBD) is characterized by excessive shopping cognitions and buying behavior that leads to distress or impairment. Found worldwide, the disorder has a lifetime prevalence of 5.8% in the US general population. Most subjects studied clinically are women (~80%), though this gender difference may be artifactual. Subjects with CBD report a preoccupation with shopping, prepurchase tension or anxiety, and a sense of relief following the purchase. CBD is associated with significant psychiatric comorbidity, particularly mood and anxiety disorders, substance use disorders, eating disorders, and other disorders of impulse control. The majority of persons with CBD appear to meet criteria for an Axis II disorder, although there is no special "shopping" personality. Compulsive shopping tends to run in families, and these families are filled with mood and substance use disorders. There are no standard treatments. Psychopharmacologic treatment studies are being actively pursued, and group cognitive-behavioral models have been developed and are promising. Debtors Anonymous, simplicity circles, bibliotherapy, financial counseling, and marital therapy may also play a role in the management of CBD. PMID- 17342216 TI - Conflicting interests and doing right. PMID- 17342215 TI - Financial conflicts of interest in psychiatry. AB - The issue of conflicts of interest has brought clinical medicine to an unprecedented crisis of credibility. The situation of psychiatry does not appear to be different from other areas of medicine. The problems caused by the increasing financial ties between the pharmaceutical industry and researchers and clinicians can be addressed only by a complex effort encompassing both the establishment of lines of support of independent researchers who are free of substantial conflicts of interest and better disclosure policies and conduct regulations as to financial ties. Such effort requires a bold shift from current, largely inadequate strategies. In the long run it may entail, however, substantial advantages to patients, clinicians, researchers, the health industry and the civil society at large. Psychiatry, in view of its humanistic and social roots, may lead this effort. PMID- 17342217 TI - One flew over the conflict of interest nest. PMID- 17342218 TI - Psychiatry: from interest in conflicts to conflicts of interest. PMID- 17342220 TI - Staying true to mission. PMID- 17342219 TI - On the propriety of collaborations between academicians and the pharmaceutical industry: an alternate viewpoint. PMID- 17342221 TI - Conflicting views on conflicts of interest in medicine. PMID- 17342222 TI - Conflicts of interest and the credibility of psychiatric research. PMID- 17342223 TI - A counter proposal to manage financial conflicts of interest in academic psychiatry. PMID- 17342224 TI - What is the impact of financial conflicts of interest on the development of psychiatry? PMID- 17342225 TI - Premorbid IQ varies across different definitions of schizophrenia. AB - The nature of the association between IQ and schizophrenia is still unclear. So far no study addressed this issue in relation to the breadth or scope of the very concept of schizophrenia. We examined the premorbid IQ in a polydiagnostic study with four classifications of schizophrenia: ICD-8/9, ICD-10, St. Louis and Flexible System-Wide. Only the ICD-10 schizophrenia patients exhibited a significantly lower premorbid IQ. There were suggestive differences between the four examined systems as well as between the ICD-10 paranoid and non-paranoid subtypes. Exploration of crucial diagnostic features of schizophrenia in relation to IQ revealed associations between low premorbid IQ and hallucinations as well as negative symptoms. It is concluded that premorbid IQ varies across different definitions of schizophrenia. PMID- 17342226 TI - Cost-effectiveness of an essential mental health intervention package in Nigeria. AB - The study aimed to describe the cost-effectiveness of a selected list of interventions for common neuropsychiatric disorders in a developing country. Using depression, schizophrenia, epilepsy, and hazardous alcohol use, a sectoral approach to cost-effectiveness analysis developed by the World Health Organization was contextualized to Nigeria. The outcome variable was the disability adjusted life years (DALYs). We found that the most cost-effective intervention for schizophrenia is a community-based treatment with older antipsychotic drugs plus psychosocial support or case management. The most cost effective interventions for depression, epilepsy, and alcohol use disorders are older antidepressants, with or without proactive case management in primary care, older anticonvulsants in primary care, and random breath testing for motor vehicle drivers, respectively. Combined into a package, these selected interventions produce one extra year of healthy life at a cost of less than US $320, which is the average per capita income in Nigeria. PMID- 17342227 TI - Australian and New Zealand contribution to international mental health research publications: a survey of high-impact journals. AB - Most mental health research published in high-impact journals originates from developed countries in North America and Western Europe and from Australia and New Zealand (ANZ), where only a minority of the world's population exists. We examined the contribution of the ANZ research community to the literature on international mental health in regard to countries outside this dominant group. A literature search was conducted with two phases: a PubMed search of mental health articles by ANZ authors in twelve high-impact local and international journals over three years (2001-2003); and a hand search of the Australian and New Zealand Journal of Psychiatry (ANZJP) over ten years (1994-2003). Four percent of mental health articles published by ANZ authors in selected high-impact journals related to international mental health in countries outside ANZ, North America and Western Europe. Six percent of the articles published in the ANZJP represented countries outside this dominant group, and ANZ authors contributed to 30% of those articles. Hong Kong and Singapore were the most frequently represented countries. Sixty-five of 78 selected articles were original research. Descriptive epidemiological studies and case reports were the commonest study designs. Psychotic illness was the most frequently studied mental disorder. Most studies were conducted in specialist mental health services. Thus, relatively little of the work published by the ANZ mental health research community in local and other high-impact journals related to international mental health in countries outside ANZ, North America and Western Europe. Countries with the lowest incomes and highest populations were particularly under-represented, and there was relatively less research in community settings or on mental health problems known to account for the highest global burden of disease. PMID- 17342228 TI - European psychiatry: moving towards integration and harmony. AB - This paper summarizes political and social changes in Europe that directly affect the training of psychiatrists and the provision of mental health services. In Western Europe the demands of service users have led to a closer integration of social and health services, and a closer working and training of health professionals. The European psychiatrist of the future will be an internationalist, familiar with the impact of culture on mental disorders and able to work in a multi-professional team. PMID- 17342229 TI - Regional cooperation in South Asia in the field of mental health. AB - The South Asian region accounts for around one fourth of the world population and one fifth of psychiatrically ill patients in the world. The region lacks mental health policies and infrastructure. Issues like community care, trained manpower, patient satisfaction and better legislation have been a focus of attention in recent years. As this region is fast developing, cooperation is needed in the field of mental health to keep pace with the other areas. Cooperation is needed to develop culturally acceptable forms of psychotherapy and new technologies for delivery of mental health services. Another area of potential cooperation is the development of a classification of mental disorders that is more informative in our setting. The development of a mental health programme and its inclusion at various levels of health care delivery has also gained precedence. As most of countries in the area have limited financial resources, the funds are to be used in the most cost-effective manner, and for this a greater collaboration amongst the countries is needed. New research needs to be undertaken in the area especially to meet the local requirements and to understand diseases in a regional perspective, but research cannot be fruitful if regional cooperation is lacking. To enhance the cooperation in mental health, world bodies like the WPA will need to come forward and bring all the countries at a common platform. The WPA has done commendable work in this regard and has always extended support to the regional bodies to uplift the mental health in this region. PMID- 17342230 TI - Integrating mental health into primary health care: local initiatives from Uganda. AB - Uganda has passed through political and bloody civil strife stretching over 40 years. Since 1987 the HIV/AIDS pandemic has compounded the problems of the country. The present paper describes some initiatives to develop mental health services in one district of the country. A bottom-up approach in the district resulted in the formation of a community-led mental health program with strong support from two self-help groups, district political leaders and district representatives in parliament. Primary health care providers at all levels of health care in the district were trained in order to make services accessible to the rural population. Further plans based on initial exploratory discussions aim to involve the education department, the welfare and probation office, prisons and police, the military, church and cultural leaders and traditional healers. These initiatives show that it is possible to empower communities to participate in the development of mental health programs in a low-income country. PMID- 17342232 TI - The WPA Regional Meeting "Mental Health in Development" (Nairobi, March 21-23, 2007). PMID- 17342231 TI - Letter to the editor. PMID- 17342233 TI - The WPA Regional Meeting "Science and Humanism" (Seoul, April 18-21, 2007). PMID- 17342234 TI - On the Road to an Impact Factor for eCAM. PMID- 17342235 TI - Role of acupuncturists in acupuncture treatment. AB - Traditional Chinese medicine (TCM) is based on a paradigm of the body different to that of modern biomedicine. Inherent characteristics of TCM necessitate an active and central role of acupuncturists in acupuncture treatment. The author looks at acupuncture in the practical context and analyzes the role of acupuncturists in diagnostic process and treatment delivery. Acupuncture as a complex non-pharmacological therapy depends solely on the acupuncturists' skills, competence and understanding of TCM theory to work. More attention should be given to this important role of acupuncturists in either clinical practice or research on acupuncture. PMID- 17342236 TI - Journeys in the country of the blind: entanglement theory and the effects of blinding on trials of homeopathy and homeopathic provings. AB - The idea of quantum entanglement is borrowed from physics and developed into an algebraic argument to explain how double-blinding randomized controlled trials could lead to failure to provide unequivocal evidence for the efficacy of homeopathy, and inability to distinguish proving and placebo groups in homeopathic pathogenic trials. By analogy with the famous double-slit experiment of quantum physics, and more modern notions of quantum information processing, these failings are understood as blinding causing information loss resulting from a kind of quantum superposition between the remedy and placebo. PMID- 17342237 TI - Does the consumption of green tea reduce the risk of lung cancer among smokers? AB - Experimental and epidemiological studies were reviewed to assess whether the consumption of green tea could reduce the risk of lung cancer in smokers. Articles published since 1990 were located by searching electronic databases PubMed, Ovid and Science Direct, using keywords 'lung cancer', 'tea' and 'smoking' without any restriction on language. After relevant articles had been located, further papers were obtained from their reference lists. Evidence from experimental studies (in vitro animal and human trials) suggested that regular intake of green tea may be protective against tobacco carcinogens. However, the mechanism behind the protective effect is only partly understood. In most of the epidemiological studies reviewed, the green tea exposure was within 5 years of the interview or follow-up, which would coincide with the induction period and latent period of lung cancer. Longer term studies are thus needed to further quantify the cancer risk. There is some evidence suggesting regular intake of green tea at high level (>3 cups per day) may reduce the risk of smokers developing lung cancer. Improvement in measuring green tea intake is required in order to confirm the evidence from epidemiological studies. PMID- 17342238 TI - Randomized controlled trials of pediatric massage: a review. AB - The existing reviews of massage therapy (MT) research are either limited to infants, adults, or were conducted prior to the publication of the most recent studies using pediatric samples. Randomized controlled trials (RCTs) of pediatric MT are reviewed. A literature search yielded 24 RCTs of pediatric MT, defined as the manual manipulation of soft tissue intended to promote health and well-being in recipients between 2 and 19 years of age. Because RCTs of pediatric MT varied considerably in the amount and types of data reported, quantitative and narrative review methods were both used. Single-dose and multiple-dose effects were examined separately. Among single-dose effects, significant reductions of state anxiety were observed at the first session (g = 0.59, P < 0.05) and the last session (g = 1.10, P < 0.01) of a course of treatment. Effects for salivary cortisol (g = 0.28), negative mood (g = 0.52) and behavior (g = 0.37) were non significant. Three of eleven multiple-dose effects were statistically significant. These were trait anxiety (g = 0.94, P < 0.05), muscle tone (g = 0.90, P < 0.01) and arthritis pain (g = 1.33, P < 0.01). Results of studies not permitting effect size calculation were judged to be generally consistent with quantitative results. MT benefits pediatric recipients, though not as universally as sometimes reported. Numerous weaknesses endemic to MT research (e.g. low statistical power, frequent failure to report basic descriptive statistics) are identified, and recommendations for future pediatric MT research are discussed. PMID- 17342239 TI - Housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats. AB - The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC) housed in home cage and left in the laboratory; restrained rats (with three subgroups) subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC) having their restrainers kept in the laboratory; restrained pyramid rats (RP) being kept in the pyramid; and restrained square box rats (RS) in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA) and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH) levels, erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats. PMID- 17342240 TI - Benefits of Zataria multiflora Boiss in Experimental Model of Mouse Inflammatory Bowel Disease. AB - Inflammatory bowel disease (IBD) is a chronic condition of the intestine with unknown etiology involving multiple immune, genetic and environmental factors. We were interested to examine the effect of total extract from Zataria multiflora Boiss, a folk medicinal plant on prevention and treatment of experimental IBD. Z. multiflora was administered (400, 600, 900 p.p.m.) through drinking water to IBD mice induced by intrarectal administration of acetic acid. Prednisolone was used as the standard drug for comparison. Biochemical, macroscopic and microscopic examinations of colon were performed. Biochemical evaluation of inflamed colon was done using assay of myeloperoxidase (MPO) activity and thiobarbituric acid reactive substances (TBARS) concentration as indicators of free radical activity and cell lipid peroxidation. The activity of MPO and lipid peroxidation products (TBARS) increased in acetic acid-treated groups while recovered by pretreatment of animals with Z. multiflora (400-900 p.p.m.) and prednisolone. Z. multiflora (600 and 900 p.p.m.) and prednisolone-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared with the acetic acid-treated group. The beneficial effect of Z. multiflora (900 p.p.m.) was comparable with that of prednisolone. The antioxidant, antimicrobial and anti inflammatory potentials of Z. multiflora might be the mechanisms by which this herbal extract protects animals against experimentally induced IBD. Proper clinical investigation should be carried out to confirm the activity in human. PMID- 17342241 TI - Electro-acupuncture at acupoint ST36 reduces inflammation and regulates immune activity in Collagen-Induced Arthritic Mice. AB - This study aimed to investigate the anti-inflammatory, anti-arthritic and immuno regulatory effects of electro-acupuncture (EA) at ST36 on Collagen-induced arthritis (CIA) in mice. Male DBA/1J mice were divided into five groups: Normal, Control, NR (needle retention), EAI and EAII. All mice except those in the normal group were immunized with Collagen II for arthritis induction. Acupuncture needles were inserted into mice ST36 and electrical currents at a frequency of 2 Hz in a continuous rectangular wave form were conducted through the needles for 15 min, 3 times a week. EA treatments were administered for 5 weeks in the EAI group and for 9 weeks in the EAII group. The mice in the NR group were acupunctured in the same manner as the EA groups and the needles were retained for 15 min without electrical stimulation. CIA incidence analysis, ELISA, histological analysis and FACS analysis were performed to evaluate the effect of EA on CIA. EA at ST36 significantly reduced CIA incidence, IL-6, TNF-a, INF gamma, collagen II antibody, IgG and IgM levels in CIA mice serum and prevented knee joint destruction. EA at ST36 also reduced CD69+/CD3e+ cells and CD11a+/CD19+ cells in CIA mice lymph nodes, and CD11b+/Gr1+ cells in CIA mice knee joints. The ratios of CD3e+ cells to CD19+ cells, and CD8+ cells to CD4+ cells were maintained closer to the normal range in the EA groups as compared with the control group or the NR group. EAII was more effective than EAI throughout all the measurements. The NR was effective as well, though less effective than EA. EA at ST36 may have an anti-inflammatory, anti-arthritic and immuno-regulatory effects on CIA in mice. The effectiveness is stronger when EA starts earlier and is applied longer. Needle retention without electrical stimulation may be effective on CIA as well, however less effective than EA. Electrical stimulation and acupoint ST36 may have synergistic effects on CIA. PMID- 17342242 TI - Recovery of small-sized blood vessels in ischemic bone under static magnetic field. AB - Effects of static magnetic field (SMF) on the vascularization in bone were evaluated using an ischemic bone model, where rat femoral artery was ligated. Magnetized and unmagnetized samarium-cobalt rods were implanted transcortically into the middle diaphysis of the ischemic femurs. Collateral circulation was evaluated by injection of microspheres into the abdominal aorta at the third week after ligation. It was found that the bone implanted with a magnetized rod showed a larger amount of trapped microspheres than that with an unmagnetized rod at the proximal and the distal region (P < 0.05 proximal region). There were no significant differences at the middle and the distal region. This tendency was similar to that of the bone mineral density in the SMF-exposed ischemic bone. PMID- 17342243 TI - Repeated 100 Hz TENS for the Treatment of Chronic Inflammatory Hyperalgesia and Suppression of Spinal Release of Substance P in Monoarthritic Rats. AB - Transcutaneous electrical nerve stimulation (TENS) has been shown to be an effective measure for pain relief. The aim of the present study was to determine the optimal intensity and interval of repeated 100 Hz TENS for the treatment of chronic inflammatory hyperalgesia in a monoarthritic pain model of the rat, and to assess the changes of the spinal substance P (SP) release in response to TENS treatment. A reliable, reproducible chronic monoarthritic pain model was produced by intra-articular injection of complete Freund's adjuvant (CFA) at single ankle joint. The efficacy of 100 Hz TENS treatments with different frequencies and intensities was compared. In the acute period (within 3 weeks) of monoarthritis, twice-a-week schedule of TENS reduced the swelling of the inflamed ankle significantly. In the stable period (4-9 weeks), however, once-a-week schedule produced a significantly better therapeutic effect on both inflammation and arthritic hyperalgesia than that of twice- or five-times-a-week schedule. Using three levels of intensity of TENS, we found that the weaker (1-1-2 mA) stimulation produced significantly better therapeutic effects. Repeated TENS produced a reduction of SP content in spinal perfusate in parallel with the progressive reduction of the arthritic pain scores. Our results suggest that (i) consecutive TENS treatments produced cumulative effect for chronic hyperalgesia, (ii) for chronic inflammatory hyperalgesia, a weaker intensity and more sparsely arranged treatment schedule may produce better therapeutic effect and (iii) a decrease in SP release may serve as one of the possible neurochemical mechanisms underlying the therapeutic effects of multiple TENS treatments on chronic inflammatory hyperalgesia. PMID- 17342244 TI - Use of magnetic nanoparticles to visualize threadlike structures inside lymphatic vessels of rats. AB - A novel application of fluorescent magnetic nanoparticles was made to visualize a new tissue which had not been detectable by using simple stereomicroscopes. This unfamiliar threadlike structure inside the lymphatic vessels of rats was demonstrated in vivo by injecting nanoparticles into lymph nodes and applying magnetic fields on the collecting lymph vessels so that the nanoparticles were taken up by the threadlike structures. Confocal laser scanning microscope images of cryosectioned specimens exhibited that the nanoparticles were absorbed more strongly by the threadlike structure than by the lymphatic vessels. Further examination using a transmission electron microscope revealed that the nanoparticles had been captured between the reticular fibers in the extracellular matrix of the threadlike structures. The emerging technology of nanoparticles not only allows the extremely elusive threadlike structures to be visualized but also is expected to provide a magnetically controllable means to investigate their physiological functions. PMID- 17342245 TI - Delayed Cell Cycle Progression and Apoptosis Induced by Hemicellulase-Treated Agaricus blazei. AB - We examined the effects of hemicellulase-treated Agaricus blazei (AB fraction H, ABH) on growth of several tumor cell lines. ABH inhibited the proliferation of some cell lines without cytotoxic effects. It markedly prolonged the S phase of the cell cycle. ABH also induced mitochondria-mediated apoptosis in different cell lines. However, it had no impact on the growth of other cell lines. ABH induced strong activation of p38 mitogen-activated protein kinase (MAPK) in the cells in which it evoked apoptosis. On the other hand, ABH showed only a weak p38 activation effect in those cell lines in which it delayed cell cycle progression with little induction of apoptosis. However, p38 MAPK-specific inhibitor inhibited both ABH-induced effects, and ABH also caused apoptosis in the latter cells under conditions of high p38 MAPK activity induced by combined treatment with TNF-alpha. These results indicate that the responsiveness of p38 MAPK to ABH, which differs between cell lines, determines subsequent cellular responses on cell growth. PMID- 17342246 TI - Chemical Constituents of Dichloromethane Extract of Cultivated Satureja khuzistanica. AB - Four compounds beta-sitosterol, beta-sitosterol-3-O-beta-d-glucopyranoside, ursolic acid and 4',5,6-trihydroxy-3', 7-dimethoxyflavone were characterized from the dichloromethane extract of the aerial parts of Satureja khuzistanica (Lamiaceae), a native medicinal plant growing in Iran, on the basis of spectral analysis and comparing with the data in literature. The natural occurrence of these compounds can be conclusive for the chemotaxonomic characterization of the genus Satureja. PMID- 17342247 TI - Efficacy of static magnetic field for locomotor activity of experimental osteopenia. AB - In order to examine the effectiveness of applying a static magnetic field (SMF) for increasing bone mineral density (BMD), we assessed the degree of osteopenia by dual-energy X-ray absorptiometry (DEXA), the metabolism measuring system, and histological examination of bone tissue in an ovariectomized (OVX) rat model. Thirty-six female Wistar rats (8 weeks old, 160-180 g) were divided into three groups. The rats in the OVX-M group were exposed to SMF for 12 weeks after ovariectomy. The ovariectomized rats in the OVX-D group were not exposed to SMF as a control. The rats in the normal group received neither ovariectomy nor exposure to SMF. Twelve-week exposure to SMF in the OVX-M group inhibited the reduction in BMD that was observed in the OVX-D group. Moreover, in the OVX rats, before exposure to SMF, there was no clear difference in the level of locomotor activity between the active and resting phases, and the pattern of locomotor activity was irregular. After exposure of OVX rats to SMF, the pattern of locomotor activity became diphasic with clear active and resting phases, as was observed in the normal group. In the OVX-M group, the continuity of the trabecular bone was maintained more favorably and bone mass was higher than the respective parameters in the OVX-D group. These results demonstrate that exposure to SMF increased the level of locomotor activity in OVX rats, thereby increasing BMD. PMID- 17342248 TI - A randomized controlled trial of tai chi for tension headaches. AB - This study examined whether a traditional low-impact mind-body exercise, Tai Chi, affects health-related quality-of-life (HRQOL) and headache impact in an adult population suffering from tension-type headaches. Forty-seven participants were randomly assigned to either a 15 week intervention program of Tai Chi instruction or a wait-list control group. HRQOL (SF-36v2) and headache status (HIT-6trade mark) were obtained at baseline and at 5, 10 and 15 weeks post-baseline during the intervention period. Statistically significant (P < 0.05) improvements in favor of the intervention were present for the HIT score and the SF-36 pain, energy/fatigue, social functioning, emotional well-being and mental health summary scores. A 15 week intervention of Tai Chi practice was effective in reducing headache impact and also effective in improving perceptions of some aspects of physical and mental health. PMID- 17342249 TI - Healing by gentle touch ameliorates stress and other symptoms in people suffering with mental health disorders or psychological stress. AB - Previous studies on healing by gentle touch in clients with various illnesses indicated substantial improvements in psychological well-being, suggesting that this form of treatment might be helpful for people with impaired quality of mental health. The purpose of this study was to evaluate the effectiveness and safety of healing by gentle touch in subjects with self-reported impairments in their psychological well-being or mental health. One hundred and forty-seven clients who identified themselves as having psychological problems received four treatment sessions. Pre- to post-treatment changes in psychological and physical functioning were assessed by self-completed questionnaires which included visual analogue scales (VAS) and the EuroQoL (EQ-5D). Participants recorded reductions in stress, anxiety and depression scores and increases in relaxation and ability to cope scores (all P < 0.0004). Improvements were greatest in those with the most severe symptoms initially. This open study provides strong circumstantial evidence that healing by gentle touch is safe and effective in improving psychological well-being in participants with self-reported psychological problems, and also that it safely complements standard medical treatment. Controlled trials are warranted. PMID- 17342251 TI - CAM and Post-Traumatic Stress Disorder. AB - In the form of the Transcendental Meditation program CAM offers a method of eliminating deep-rooted stress, the efficacy of which has been demonstrated in several related studies. Any discussion of CAM and post-traumatic stress disorder should include a study of its application to Vietnam War Veterans in which improvements were observed on all variables, and several participants were able to return to work after several years of being unable to hold a job. The intervention has been studied for its impact on brain and autonomic nervous system function. It has been found to be highly effective against other stress related conditions such as hypertension, and to improve brain coherence-a measure of effective brain function. It should be considered a possible 'new and improved mode of treatment' for PTSD, and further studies of its application made. PMID- 17342250 TI - Electro-acupuncture in relieving labor pain. AB - To study the efficacy of electro-acupuncture for the relief of labor pain, and to build a better understanding of how electro-acupuncture might influence the neuroendocrine system, 36 primiparas were randomly divided into an electro acupuncture group and a control group. Assessments of pain intensity and degree of relaxation during labor were analyzed. The differences between the electro acupuncture group and the control group on the concentration of beta-endorphin (beta-EP) and 5-hydroxytryptamine (5-HT) in the peripheral blood were compared. The electro-acupuncture group was found to exhibit a lower pain intensity and a better degree of relaxation than the control group (p = 0.018; p = 0.031). There existed a significant difference in the concentration of beta-EP and 5-HT in the peripheral blood between the two groups at the end of the first stage (p = 0.037; p = 0.030). Electro-acupuncture was found to be an effective alternative or complementary therapy in the relief of pain during labor. The benefit of electro acupuncture for relieving labor pain may be based on the mechanism of producing a synergism of the central nervous system (CNS) with a direct impact on the uterus through increasing the release of beta-EP and 5-HT into the peripheral blood. PMID- 17342252 TI - Assessment of the impact of implementing the Baby-Friendly Hospital Initiative. AB - OBJECTIVE: To evaluate the impact of the Baby-Friendly Hospital Initiative on the breastfeeding practices of mothers from the urban area of Montes Claros, MG, Brazil. METHODS: A comparative analysis was performed of two cross-sectional breastfeeding indicator studies with randomized samples of children under 2 years of age. One study was carried out before and the other after the Baby-Friendly Hospital Initiative had been implemented throughout all public pregnancy and childbirth care services in the city. Kaplan-Meyer survival curves were constructed for different breastfeeding patterns. Log rank testing was used to calculate the level of significance of differences between curves for before and after the Initiative. RESULTS: The survival curves demonstrate that breastfeeding rates increased during the study period. The log rank test detected significance for increases in all patterns of breastfeeding (p < 0.000). Median overall breastfeeding duration increased from 8.9 to 11.6 months and median duration of exclusive breastfeeding rose from 27 days to 3.5 months. CONCLUSIONS: Implementation of the Baby-Friendly Hospital Initiative in all public maternity units in Montes Claros significantly increased breastfeeding rates in the city. Since the ideal state of affairs has not yet been reached, further strategies must be implemented to promote and support breastfeeding practices. PMID- 17342253 TI - Structure and function of the NS1 protein of influenza A virus. AB - The avian influenza A virus currently prevailing in Asia causes fatal pneumonia and multiple organ failure in birds and humans. Despite intensive research, understanding of the characteristics of influenza A virus that determine its virulence is incomplete. NS1A protein, a non-structural protein of influenza A virus, was reported to contribute to its pathogenicity and virulence. NS1A protein is a multifunctional protein that plays a significant role in resisting the host antiviral response during the influenza infection. This review briefly outlines the current knowledge on the structure and function of the NS1A protein. PMID- 17342254 TI - Lipopolysaccharide enhances the production of nicotine-induced prostaglandin E2 by an increase in cyclooxygenase-2 expression in osteoblasts. AB - Previous studies have indicated that lipopolysaccharide (LPS) from Gram-negative bacteria in plaque induces the release of prostaglandin E(2) (PGE(2)), which promotes alveolar bone resorption in periodontitis, and that tobacco smoking might be an important risk factor for the development and severity of periodontitis. We determined the effect of nicotine and LPS on alkaline phosphatase (ALPase) activity, PGE(2) production, and the expression of cyclooxygenase (COX-1, COX-2), PGE(2) receptors Ep1>4, and macrophage colony stimulating factor (M-CSF) in human osteoblastic Saos-2 cells. The cells were cultured with 10(-3) M nicotine in the presence of 0, 1, or 10 mug/ml LPS, or with LPS alone. ALPase activity decreased in cells cultured with nicotine or LPS alone, and decreased further in those cultured with both nicotine and LPS, whereas PGE(2) production significantly increased in the former and increased further in the latter. By itself, nicotine did not affect expression of COX-1, COX-2, any of the PGE(2) receptors, or M-CSF, but when both nicotine and LPS were present, expression of COX-2, Ep3, Ep4, and M-CSF increased significantly. Simultaneous addition of 10(-4) M indomethacin eliminated the effects of nicotine and LPS on ALPase activity, PGE(2) production, and M-CSF expression. Phosphorylation of protein kinase A was high in cells cultured with nicotine and LPS. These results suggest that LPS enhances the production of nicotine-induced PGE(2) by an increase in COX-2 expression in osteoblasts, that nicotine-LPS induced PGE2 interacts with the osteoblast Ep4 receptor primarily in autocrine or paracrine mode, and that the nicotine-LPS-induced PGE(2) then decreases ALPase activity and increases M-CSF expression. PMID- 17342255 TI - Possible role of histone H1 in the regulation of furin-dependent proprotein processing. AB - Histone H1 and its C-terminal lysine rich fragments were recently found to be potent inhibitors of furin, a mammalian proprotein convertase. However, its role in the regulation of furin-dependent proprotein processing remains unclear. Here we report that histone H1 efficiently blocks furin-dependent pro-von Willebrand factor (pro-vWF) processing in a dose-dependent manner. Coimmunoprecipitation and immunofluorescence studies confirmed that histone H1 could interact with furin, and the interaction mainly took place on the cell surface. We noted that histone H1 was released from cells undergoing necrosis and apoptosis induced by H(2)O(2). Our findings suggested that histone H1 might be involved in extracellular and/or intracellular furin regulation. PMID- 17342256 TI - p53 promoter-based reporter gene in vitro assays for quick assessment of agents with genotoxic potential. AB - The p53 promoter-based green fluorescent protein (GFP) and luciferase reporter gene assays have been established for detecting DNA damage induced by genotoxic agents. To evaluate the system, NIH3T3 cells transfected with either pHP53-GFP or pMP53-GFP construct were treated with mitomycin or 5-fluorouracil. Expression of the GFP reporter gene was significantly and specifically induced in the cells exposed to mitomycin or 5-fluorouracil. Then we treated NIH3T3 cells harboring pHP53-Luc or pMP53-Luc vector with mitomycin, 5-fluorouracil or cisplatin at various concentrations. Similarly, exposure of the cells to these agents with genotoxic potentials resulted in a dose-dependent induction in luciferase reporter gene expression. Thus, these in vitro reporter gene assays could provide an ideal system for quick assessment or screening of agents with genotoxic potential. PMID- 17342257 TI - Cloning and characterization of genes encoded in dTDP-D-mycaminose biosynthetic pathway from a midecamycin-producing strain, Streptomyces mycarofaciens. AB - Two subclusters from Streptomyces mycarofaciens, a midecamycin producer, were cloned and partially sequenced. One region was located at the 5' end of the mid polyketide synthase (PKS) genes and contained the genes midA, midB and midC. The other region was at the 3' end of the PKS genes and contained midK, midI and midH. Analysis of the nucleotide sequence revealed that these genes encode dTDP glucose synthase (midA), dTDP-glucose dehydratase (midB), aminotransferase (midC), methyltransferase (midK), glycosyltransferase (midI) and an assistant gene (midH). All of these genes are involved in the biosynthesis of dTDP-D mycaminose, the first deoxysugar of midecamycin, and in transferring the mycaminose to the midecamycin aglycone in S. mycarofaciens. Similar to gene pairs desVIII/desVII in S. venezuelae and tylMIII/tylMII in S. fradiae, the product of midH probably functions as an auxiliary protein required by the MidI protein for efficient glycosyltransfer in midecamycin biosynthesis. PMID- 17342258 TI - Expression, characterization and immunogenicity of a major outer membrane protein from Vibrio alginolyticus. AB - Vibrio alginolyticus is one of the Vibrio pathogens common to humans and marine animals. During infection and induction of the host immune response, outer membrane proteins of bacteria play an important role. In this study, an outer membrane protein gene (ompW) was cloned from V. alginolyticus and expressed in Escherichia coli. The 645 bp open reading frame (ORF) encodes a protein of 214 amino acid residues with a predicted molecular weight of 23.3 kDa. The amino acid sequence showed a high identity with that of Photobacterium damselae (96.2%) and Vibrio parahaemolyticus (94.4%). The alignment analysis indicated that OmpW was highly conserved. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the gene was over-expressed in E. coli BL21(DE3). Western blot analysis revealed that the expressed protein had immunoreactivity. The recombinant protein was purified by affinity chromatography on Ni-NTA Superflow resin. Large yellow croaker vaccinated with the purified OmpW showed significantly increased antibody to OmpW, which could resist the infection by V. alginolyticus. A specific antibody was detected by enzyme-linked immunosorbent assay. This study suggested that the conserved OmpW could be an effective vaccine candidate against infection by V. alginolyticus. PMID- 17342259 TI - Diverse effects of L-arginine on cardiac function of rats subjected to myocardial ischemia and reperfusion in vivo. AB - In vivo administration of L-arginine at different time points during the course of myocardial ischemia and reperfusion (MI/R) has been shown to differentially regulate postischemic apoptosis. Cardiac function is one of the most important indexes used to judge the degree of myocardial injury. The present study attempted to determine whether in vivo administration of L-arginine at different stages of MI/R has a diverse influence on cardiac function of ischemic reperfused hearts and, if so, to investigate the mechanisms involved. Male adult rats were subjected to 30 min myocardial ischemia followed by 5 h reperfusion. An intravenous L-arginine bolus was given either 10 min before and 50 min after reperfusion (early treatment) or 3 h and 4 h after reperfusion (late treatment). Early treatment with L-arginine markedly increased the left ventricular systolic pressure (LVSP) and dP/dt(max), and decreased myocardial nitrotyrosine content. In strict contrast, late treatment with L-arginine resulted in a significant decrease in LVSP and dP/dt(max) from 4 h to 5 h after reperfusion, and increase in toxic peroxynitrite formation as measured by nitrotyrosine. These results suggest that the administration of L-arginine at different time points during the course of MI/R leads to diverse effects on cardiac dysfunction. Early supplementation decreased the nitrative stress and improved left ventricular function. However, late treatment with L-arginine increased the formation of peroxynitrite and aggravated cardiac functional injury. PMID- 17342260 TI - Construction and functional analysis of a lentiviral expression vector containing a scavenger receptor (SR-PSOX) that binds uniquely phosphatidylserine and oxidized lipoprotein. AB - The aim of this study is to construct a lentiviral expression vector containing a scavenger receptor (SR-PSOX) that binds with uniquely phosphatidylserine and oxidized lipoprotein with six histidine tags and to investigate the function of SR-PSOX in atherosclerosis. We utilize the ViraPower lentiviral expression system which was efficient to deliver in vitro or in vivo the target gene into dividing and non-dividing mammalian cells using an enhanced biosafety replication incompetent lentivirus. The blunt-end sequence was amplified using the reverse transcription-polymerase chain reaction and directional TOPO cloning reaction. Through a pair of the cytomegalovirus forward primer and the reverse primer of SR PSOX, the correct clones were identified by polymerase chain reaction and sequencing. The ViraPower packaging mix and SR-PSOX-pLenti6/V5 TOPO expression plasmid were co-transfected into the 293FT cell line using Lipofectamine 2000. The expression of endogenous and exogenous SR-PSOX as well as tumor necrosis factor (TNF)-alpha protein in various foam cell models at different time points were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot and indirect immunofluorescence assay. Western blot and immunofluorescence analysis confirmed that the expressions of SR-PSOX and TNF alpha protein were upregulated in foam cell models. Our data suggested that the overexpression of recombinant human SR-PSOX protein can promote foam cell formation and upregulate the expression of the inflammatory factor TNF-alpha. PMID- 17342261 TI - Satellite RNA-mediated reduction of cucumber mosaic virus genomic RNAs accumulation in Nicotiana tabacum. AB - Satellite RNAs (satRNAs) are molecular parasites that interfere with the pathogenesis of the helper viruses. In this study, the relative accumulation of cucumber mosaic virus (CMV)-Fny genomic RNAs with or without satRNAs were quantitatively analyzed by real-time RT-PCR. The results showed that satRs apparently attenuated the symptoms of CMV-Fny on Nicotiana tabacum by depressing the accumulation of CMV-Fny genomic RNAs, tested as open reading frames. The accumulation of CMV-Fny 1a, 2a, 2b, 3a, and CP genes was much higher than that of CMV-Fny with satRs added (CMV-Fsat), at different inoculation times. CMV FnyDelta2b, in which the complete 2b gene and 41 amino acids at the C-terminal of the 2a gene were deleted, caused only a slight mosaic effect on N. tabacum seedlings, similar to that of CMV-Fsat, but the addition of satRs to CMV FnyDelta2b showed further decrease in the accumulation of CMV-FnyDelta2b genomic RNAs. Our results indicated that the attenuation of CMV, by adding satRs or deleting the 2b gene, was due to the low accumulation of CMV genomic RNAs, and that satRNA-mediated reduction of CMV genomic RNAs accumulation in N. tabacum was possibly related to the 2b gene. PMID- 17342262 TI - Small interfering RNA-mediated caveolin-1 knockout on plasminogen activator inhibitor-1 expression in insulin-stimulated human vascular endothelial cells. AB - Using human vascular endothelial cells (ECV304) as the target, we studied the effect of caveolin (CAV)-1 in the course of insulin-stimulated expression of plasminogen activator inhibitor (PAI)-1. The appropriate single-stranded oligonucleotides representing the RNAi CAV-1 gene were analyzed by Ambion software. After annealing to generate double-stranded oligonucleotides (ds oligo), it was cloned into the pENTR/U6 entry vector containing RNA polymerase III expression element by T4 DNA ligase. The short hairpin (shRNA) sequences transferred from the pENTR/U6 entry were cloned into the pLenti6/BLOCK-iT-DEST vector with an LR recombination reaction. After identification by sequencing, we successfully constructed the CAV-1 RNAi lentiviral expression system using Gateway technology. Silencing efficiency was assayed by real-time reverse transcription-polymerase chain reaction, immunofluorescence staining and Western blotting. ECV304 cells were cultured in the medium containing different concentrations of insulin (1x10(-9) to 1x10(-7) M) with the CAV-1 gene silenced or not. The expression level and subcellular localization of PAI-1 and CAV-1 were compared using reverse transcription-polymerase chain reaction, immunofluorescence staining and Western blot assay. The results showed that the potent inhibition of CAV-1 expression could reach 85%, and it was specific to the CAV-1-derived shRNA, not the S100A13-derived shRNA. There was no dramatic difference in PAI-1 expression between the RNAi+ and RNAi- ECV304 cells incubated with physiological insulin, but PAI-1 protein did accumulate under the cell membrane. As the concentration of insulin increased, the expression of PAI-1 was up-regulated, whereas the expression of CAV-1 attenuated. Furthermore, PAI-1 clearly augmented after CAV-1 knockdown. These results indicated that hyperinsulinism could promote PAI-1 expression by inhibiting CAV-1, and stabilizing or up-regulating CAV-1 expression in endothelial cells might reduce complications of the great vessels and capillary vessels in diabetes. PMID- 17342263 TI - Equilibrium water sorption characteristics of the human nail. AB - The physical and transport properties of keratinized tissues are closely related to their water content. This report presents water uptake and desorption isotherms for the human nail and compares them with those of wool, horn, hair, and stratum corneum. Nail absorbed a maximum of approximately 0.3 g H(2)O/g dry tissue, with the shape and magnitude of the isotherm most closely resembling horn. Hysteresis between uptake and desorption was observed, similar to that of other keratins. The shape of the isotherms was adequately described by both the D'Arcy-Watt and Guggenheim-Anderson-deBoer (GAB) models; however, small positive deviations from both models were found in the relative humidity range, 30-60%. Directionally better fits to the data were found with the D'Arcy-Watt model. This analysis suggests that most of the water in the tissue was in a strongly bound state, consistent with observations made by other techniques. PMID- 17342264 TI - Structural analysis of the cell membrane complex in the human hair cuticle using microbeam X-ray diffraction: relationship with the effects of hair dyeing. AB - This article deals with the structure of the cell membrane complex (CMC) in the human hair cuticle. The microbeam X-ray provided a pattern of small-angle scattering from the CMC in the cuticle with no sample preparations, including slicing and pre-staining of hair. The thickness of the beta- and delta-layers, substructure in CMC, was estimated by analysis of the scattering pattern. We used hair samples extracted with several solvents, and found that solvent extraction changed the thickness of the beta- and delta-layers in a manner dependent on the type of solvent. Extraction of hair with solvent was also shown to have effects on the extent of dyeing. There was a high correlation between the extent of dyeing and the thickness of the delta-layer, i.e., a thin layer tended to show a high amount of dyeing, whereas there was no significant correlation between the thickness of the beta-layer and the extent of dyeing. PMID- 17342265 TI - Inhibitory effects of natural plants of Jeju Island on elastase and MMP-1 expression. AB - In order to search for new active cosmetic ingredients of natural origin, we screened about 60 plants collected from Jeju Island, which is located in the southernmost part of the Republic of Korea. We investigated their free radical scavenging activity, elastase inhibition activity, and reduction of MMP-1 mRNA expression for the development of anti-aging ingredients as raw materials for use in cosmetics. In the free radical scavenging capacity assay, 12 extracts, including Typha orientalis (seed) and Torreya nucifera (leaf), showed significant free radical scavenging activity (up to SC(50)<30 microg/ml). Among these extracts, Nymphaea tetragona (rhizome) extract showed the highest free radical scavenging activity (SC(50)=4.7 microg/ml). In the anti-elastase inhibition assay, seven extracts, including Typha orientalis (seed) and Persicaria hydropiper (whole plant), showed high inhibitory activity (>50% at 100 mug/ml). Among these extracts, Persicaria hydropiper (whole plant) extract showed the highest elastase inhibition activity (IC(50) = 46.7 mug/ml). In the MMP-1 expression assay using RT-PCR, Typha orientalis (seed), Pyrrosia hastata (root), and Capsicum annum (whole plant) showed slightly lower inhibition activity than EGCG, which was used as a control. Furthermore, four extracts, including Persicaria hydropiper (whole plant), Filipendula glaberrima (root), Nymphaea tetragona (root), and Camellia japonica (leaf), completely inhibited the expression of MMP-1 in human fibroblast cells. The results showed that four of the 60 plant extracts may hold potential for use as natural active ingredients for anti-aging cosmetics. PMID- 17342266 TI - High-performance liquid chromatographic determination of arbutin in skin whitening creams and medicinal plant extracts. AB - A high-performance liquid chromatographic method was developed for quantitative analysis of arbutin. The arbutin was separated on an ODS Hypersil C(18) column with a mobile phase of water:methanol:0.1 M hydrochloric acid (89:10:1, v/v/v). The level of arbutin was measured by means of UV detection at 222 nm. The optimum conditions for arbutin quantitative analysis were investigated. The calibration curve was found to be linear up to 1,000 microg/ml(-1) of arbutin concentration, and the working calibration curve for arbutin determination over the range 0.5 30.0 microg/ml(-1) of arbutin (r(2)=0.9999) was established. The relative standard deviations for intraday and interday were found to be 0.98% and 1.15%, respectively. A detection limit (3sigma) and quantitation limit (10sigma) of 0.02 microg/ml(-1) and 0.2 microg/ml(-1), respectively, and a mean percentage recovery of the spiked arbutin of 99.88 +/- 1.12% were obtained. The proposed method has been applied to the determination of arbutin in commercial skin-whitening creams (Arbuwhite cream, Super Whitening cream, and Shiseido cream) with average contents of 7.60, 5.30, and 57.90 mg/g(-1), respectively. It was also applied to the determination of arbutin in medicinal plant extracts from Betula alnoides Buch. Ham., Clerodendrum petasites S. Moore, Curculigo latifolia Dryand. Var. latifolia, and Hesperethusa crenulata (Roxb.) Roem, levels of which were found to be 3.50, 1.50, 1.10, and 0.12 microg/g(-1), respectively (no article reported in the literature about arbutin analysis). The proposed HPLC method is rapid, simple, and selective for routine analysis. PMID- 17342267 TI - Clay facial masks: physicochemical stability at different storage temperatures. AB - Clay facial masks--formulations that contain a high percentage of solids dispersed in a liquid vehicle--have become of special interest due to specific properties presented by clays, such as particle size, cooling index, high adsorption capacity, and plasticity. Although most of the physicochemical properties of clay dispersions have been studied, specific aspects concerning the physicochemical stability of clay mask products remain unclear. This work aimed at investigating the accelerated physicochemical stability of clay mask formulations stored at different temperatures. Formulations were subjected to centrifuge testing and to thermal treatment for 15 days, during which temperature was varied from -5.0 degrees to 45.0 degrees C. The apparent viscosity and visual aspect (homogeneity) of all formulations were affected by temperature variation, whereas color, odor, and pH value remained unaltered. These results, besides the estimation of physicochemical stability under aging, can be useful in determining the best storage conditions for clay-based formulations. PMID- 17342274 TI - Visual disturbances in dengue fever: an answer at last? AB - Visual disturbances in dengue infection are uncommon but may result in permanent visual impairment. We report a 32-year-old Chinese woman with dengue infection and she developed retinal haemorrhage, retinal vasculitis and macular detachment. Autoimmune screen revealed a low C4 complement level, possibly due to partial C4 complement deficiency. The patient was treated with steroids and there was significant improvement in her vision. Partial C4 deficiency predisposes to autoimmune disease, and patients with pre-existing low C4 levels may be susceptible to ocular complications in dengue infection. Interestingly, previous case reports of ophthalmic complications of dengue infection occurred in young female patients, who are likewise predisposed to autoimmune disease. In conclusion, in individuals predisposed to autoimmune disease (females and patients with partial C4 deficiency), dengue infection may provide the antigenic trigger for immune complex deposition and retinal vasculitis. Steroids may have an important role in the treatment of this condition. PMID- 17342275 TI - Chronic neutrophilic leukaemia. AB - Chronic neutrophilic leukaemia is a rare myeloproliferative disease characterised by splenomegaly, sustained neutrophilia, raised vitamin B12 level and absence of the Philadelphia chromosome. We report a 74-year-old man who presented first with Sweet's syndrome and subsequently leukocytosis. He had splenomegaly, a raised vitamin B12 level, serum uric acid and neutrophil alkaline phosphatase score. Cytogenetic study of the marrow was normal and peripheral blood for BCR-ABL gene transcript was not detectable. He subsequently passed away with bronchopneumonia. PMID- 17342276 TI - Pure choriocarcinoma of testis with rare gingival and skin metastases. AB - A 22-year-old man presented with complaints of gingival and skin lesions. Physical examination revealed the presence of two nodular lesions, one over the sternum, 3 cm in size, and another, on the right side of chin, 1 cm in size. There was another fleshy soft tissue deposit over the left lower gingiva, in the oral cavity. He had noticed these lesions ten days prior to his visit to the hospital. In addition, there was left testicular non-tender swelling which had been present for two months, but was not investigated. Fine-needle aspiration cytology from skin and gingival lesions was suggestive of metastatic deposits. Patient underwent left high orchidectomy, and histopathological examination was consistent with the diagnosis of pure choriocarcinoma. Although rare, cases of testicular neoplasms and especially choriocarcinoma of the testis leading to skin metastases have been reported, but case reports of choriocarcinoma of testis metastatic to gingiva have been reported exceptionally in the English literature. We report this unique case of a young man with pure choricarcinoma of testis with unusual gingival and skin metastases. PMID- 17342277 TI - Intratracheal metastasis secondary to soft tissue liposarcoma. AB - Intratracheal metastasis from non-pulmonary neoplasm is extremely rare. We report a 53-year-old woman presenting with upper airway obstruction and stridor due to intratracheal metastasis from latissimus dorsi liposarcoma. Chest computed tomography revealed an intratracheal mass leading to intralumimal obstruction of the upper airway. At rigid bronchoscopy, a 2-cm intratracheal mass was identified and resected with endobronchial electrosurgery to establish a satisfactory airway with marked symptomatic benefit. We discuss this unusual metastatic presentation. PMID- 17342278 TI - Laryngocoele presenting as acute airway obstruction. AB - A laryngocoele is an abnormal dilatation of the laryngeal saccule. Symptomatic laryngocoeles can present as rapidly developing airway obstruction. In this case report of a 37-year-old man with a laryngocoele, we discuss the management dilemma presented by his repeated flight from the hospital prior to definitive treatment. This resulted in repeated admissions with life-threatening airway symptoms, culminating in emergency tracheostomies. Surgical excision of the laryngocoele was not achieved until the third presentation. We recommend early surgical intervention in patients who are potentially non-compliant to treatment or follow-up. A brief literature review of laryngocoele, as well as management of the difficult airway, are also discussed. PMID- 17342279 TI - Primary splenic flexure volvulus. AB - Primary splenic flexure volvulus is a rare entity. We report an acute presentation of primary splenic flexure volvulus with gangrene in a 24-year-old man. Radiograph showed a massively-dilated large bowel loop with a coffee-bean sign. At emergency laparotomy, a distended and gangrenous splenic flexure was found, with absence of all three ligamentous attachments of the splenic flexure. PMID- 17342280 TI - A persistent left superior vena cava. AB - Persistent left superior vena cava is the most common form of anomalous venous drainage involving the superior vena cava, and represents persistence of the left horn of the embryonic sinus venosus, which normally involutes during normal development to become the coronary sinus. Almost always, a persistent left superior vena cava enters the right atrium through the orifice of an enlarged coronary sinus. In this case report of a 60-year-old male cadaver, we describe a persistent left superior vena cava and discuss its embryology and clinical significance. PMID- 17342281 TI - Compressive femoral neuropathy: a rare complication of anticoagulation. AB - The most common coagulation disorder associated with warfarin use is bleeding, but compressive femoral neuropathy is an unusual presentation. A 63-year-old man with compressive femoral neuropathy from an iliacus haematoma is reported. The diagnosis was confirmed on magnetic resonance imaging and treated conservatively with good clinical response and radiological evidence of resolution. PMID- 17342283 TI - Teaching of anatomy in the new millennium. PMID- 17342282 TI - Laparoscopic management of iatrogenic high rectovaginal fistulas (Type VI). AB - Most rectovaginal fistulas are acquired. Obstetrical trauma and types of surgery such as laparoscopic-assisted vaginal hysterectomy may cause high rectovaginal fistulas. The high fistulas are repaired by abdominal approach, while middle or low fistulas are best approached perineally. There are not many reports of totally-laparoscopic repair available in the literature. We present two patients who had a (Type VI) high rectovaginal fistula following laparoscopicassisted vaginal hysterectomy. Laparoscopic repair was successfully performed by suturing the defects and fixing an omental patch between the rectum and vagina. The postoperative period was uneventful. Diagnosis and exact location of the fistula is critical in the management. Laparoscopic repair of high rectovaginal fistulas is feasible in most patients. Proper identification of tissue planes and good laparoscopic suturing technique is crucial for success. The issue of rectovaginal fistulas needs to be addressed in this era of laparoscopy, with particular reference to laparoscopy-assisted vaginal hysterectomy. PMID- 17342284 TI - Theodor Bilharz (1825-1862): discoverer of schistosomiasis. PMID- 17342285 TI - Risk factors associated with low bone mineral content in very low birth weight infants. AB - INTRODUCTION: We report part of the findings of a study conducted to determine the correlation between bone mineral content (BMC) and biochemical bone markers in very low birth weight (VLBW) infants. METHODS: This was a cross-sectional study, carried out between August 2001 and June 2004 in the neonatal intensive care unit of Hospital Universiti Kebangsaan Malaysia. Whole body BMC was measured by dual energy X-ray absorptiometry in 41 VLBW infants. RESULTS: The mean BMC/kg body weight was 25.8 (standard deviation [SD] 11.2) g per kg. The BMC of these infants had significant negative correlation with their birth weight (r equals 0.31, p-value equals 0.048). There was no significant difference in the mean BMC between different races and gender. The infants were divided into two groups based on the course of prematurity: "non-complicated" and "complicated" groups because of the lack of "healthy reference population" data for normal BMC values in premature infants. The "non-complicated" group (30) had received ventilator assistance for less than seven days, tolerated full enteral nutrition before the age of two weeks, had no sepsis or necrotising enterocolitis and did not receive regular diuretic or steroid treatment. The cut-off level for a desirable BMC per kg in VLBW infants was obtained from a value corresponding to one SD below the mean of the "non-complicated" group, i.e., 17.4 g per kg. Eight (19.6 percent) infants had BMC less than this value. Multilinear regression analysis of demographical characteristics, maternal factors, neonatal complications and nutrition received revealed that heavier birth weight (p-value equals 0.007) and longer duration of parenteral nutrition (p-value equals 0.03) were associated with lower BMC. CONCLUSION: VLBW infants who required parenteral nutrition for longer periods were at higher risk to having poorer bone mineralisation. PMID- 17342287 TI - Reheating of soy oil is detrimental to bone metabolism in oestrogen deficient rats. AB - INTRODUCTION: The short-term and long- term effects of heated soy oil on bone metabolism in ovariectomised Sprague-Dawley rats were studied. METHODS: Three month-old female rats, were divided into five groups: normal control (NC); ovariectomised control (OVXC); ovariectomised and fed rat chow with added fresh soybean oil (SOF) or once-heated soy oil (SO1) or five-times-heated soy oil (SO5). Short-term parameters measured after one month were serum interleukin-6 (IL-6) and osteocalcin. Long-term parameters measured after six months were the structural bone histomorphometrical parameters. Vitamin E content in the soy oil subjected to the different heating treatments were also measured. RESULTS: Rats in the SO5 group had higher levels of IL-6 after one month compared to the other four groups. Osteocalcin levels in the SO1 and SO5 groups remained high after treatment, while those in the NC and SOF groups declined. After six months, bone mass declined in the SO5 group. Vitamin E assay in the oils showed that levels of alpha-tocopherol decreased after heating the oil once and five times, while levels of gamma- and delta-tocopherols only declined after heating five times. CONCLUSION: Repeated heating of soy oil destroyed the tocopherols causing raised serum IL-6 and osteocalcin levels, leading to increased bone resorption and osteoporosis in the long term. PMID- 17342286 TI - Effects of vitamin E supplementation on bone metabolism in nicotine-treated rats. AB - INTRODUCTION: Nicotine has been shown to exert negative effects on bone. This study determined whether vitamin E supplementation is able to repair the nicotine induced adverse effects in bone. METHODS: 24 male rats were divided into three groups. The fi rst group was the baseline control and killed untreated at the beginning of the study. Groups 2 and 3 received nicotine at 7 mg per kg for three months but during the second and third months, group 2 was supplemented with alpha-tocopherol (N+ATF) while group 3 was given palm tocotrienol mixture (N+TT). Serum interleukin-1 (IL-1), serum interleukin-6 (IL-6), serum osteocalcin, urine deoxypyridinoline (DPD) and bone calcium content were measured. RESULTS: Palm tocotrienol mixture was able to prevent the increment of IL-1 and IL- 6 due to nicotine treatment. No changes were seen in the osteocalcin levels, but the N+ATF group had lower urine DPD levels after treatment. However, bone-remodelling index revealed no significant changes. No significant differences were seen in the femoral bone calcium content results, although the fourth lumbar bone calcium content was reduced in both groups with 66.5 percent reduction in the N+ATF group and 59.6 percent reduction in the N+TT group. CONCLUSION: Palm tocotrienol mixture was better than alpha-tocopherol in reversing the effects of nicotine on IL-1 and IL-6. Both forms of vitamin E were not able to restore the nicotine induced bone calcium loss, but the N+ATF group suffered a greater loss. Tocotrienol seemed to be superior to alpha-tocopherol in combating against the adverse effect of nicotine. PMID- 17342288 TI - Vitamin D levels for optimum bone health. AB - INTRODUCTION: Vitamin D deficiency was assessed previously on the basis of rickets and osteomalacia, which represent an extreme end of the spectrum. As a result of this, many clinically-asymptomatic patients go undetected. As vitamin D deficiency results in secondary hyperparathyroidism, we propose to use the normalisation of intact parathyroid hormone (iPTH) as a surrogate marker for assessing the adequacy of vitamin D nutrition. METHODS: A descriptive study was undertaken on 195 premenopausal Pakistani women. 25-hydroxy-cholecalciferol and iPTH levels were measured by standard laboratory techniques. RESULTS: The minimum level of vitamin D required to keep iPTH below 53 pg/dL was found to be 16 ng/ml with a 95 percent confidence interval of 13.8 and 18.2. Existing normal range is 9-36 ng/ml. CONCLUSION: Normalisation of iPTH if taken as a criterion for judging vitamin D deficiency can lead to detection of clinically asymptomatic patients. The simplicity, low cost of correction, and the potential beneficial skeletal and non-skeletal consequences of doing so makes it essential that this criterion be used to redefine the optimal vitamin D levels. This should be internationally standardised and made available to clinicians. PMID- 17342289 TI - Identification of risk factors for urinary retention following total knee arthroplasty: a Singapore hospital experience. AB - INTRODUCTION: Urinary retention is associated with an increased rate of urinary tract infections and deep sepsis following total joint arthroplasty. This study was carried out to investigate the incidence of urinary retention following total knee arthroplasty in a Singapore hospital, and to identify risk factors associated with the development of this complication in our patient population. METHODS: The charts of 125 consecutive patients who underwent primary total knee arthroplasty between January and December 2004 were reviewed. The incidence of postoperative urinary retention was correlated with the following factors: age, gender, choice of anaesthesia, duration of surgery, and analgesic technique. Statistical analysis was performed with univariate and multivariate logistic regression models. There were 109 female and 16 male patients. The mean age of the patients was 67.5 years (range, 50-86 years). RESULTS: Ten patients developed urinary retention, giving an overall rate of 8.0 percent (95 percent confidence interval [CI], 3.9-4.2). Male gender (odds-ratio [OR] is 5.9; 95 percent CI, 1.2 29.5; p-value is 0.03) and epidural analgesia (OR is 7.6; 95 percent CI, 1.7 35.0; p-value is 0.009) were found to be the only factors significantly associated with postoperative urinary retention. Patient age, duration of surgery and choice of anaesthesia were not found to be significantly associated with urinary retention. CONCLUSION: In our patient population, male patients and patients receiving epidural postoperative analgesia are at increased risk of developing urinary retention following total knee arthroplasty. PMID- 17342290 TI - Urological complications of laparoscopic hysterectomy: a four-year review at KK Women's and Children's Hospital, Singapore. AB - INTRODUCTION: This review assessed the incidence, predisposing conditions, and key surgical steps, where urological injuries occurred during laparoscopic hysterectomies at the Minimally Invasive Surgery Unit, KK Women's and Children's Hospital over a four-year period. METHODS: A retrospective review of 495 cases of laparoscopic assisted vaginal hysterectomies (LAVH) and total laparoscopic hysterectomy (TLH) from January 2001 to December 2004 was conducted. RESULTS: A total of eight urological injuries occurred, all within the initial two years of review. There were seven unintentional bladder injuries occurring at LAVH during dissection of the bladder off the uterovaginal attachment. The associated factors included previous caesarean section and fibroids. All bladder injuries were diagnosed and repaired intraoperatively with no long-term complications. A single case of ureteric injury occurred with TLH. The patient presented on the ninth postoperative day with fever and continuous vaginal discharge. The most likely aetiology was thermal damage from electrocautery used to secure haemostasis of the uterine artery pedicle. Ureteric re-implantation was eventually required in the patient. CONCLUSION: Urological injuries occurred in 1.6 percent of laparoscopic hysterectomies in our hospital. The predisposing factors include previous caesarean surgery, multiple fibroids and severe endometriosis. A definite learning curve exists with laparoscopic hysterectomy with a thorough knowledge of pelvic anatomy being an essential prerequisite for advanced pelvic surgery. Similarly, good exposure of the surgical field, vigilant dissection and judicious use of electro-surgery are important practices to adopt to prevent injuries. PMID- 17342291 TI - The pursuit of thinness: an outcome study of anorexia nervosa. AB - INTRODUCTION: Anorexia nervosa (AN) is a growing problem among young female Singaporeans. We studied the demographics and follow-up data of AN patients referred to dietitians for nutritional intervention. METHODS: A retrospective nutritional notes review was done on 94 patients seen from 1992 to 2004. All patients were given nutritional intervention, which included individualised counselling for weight gain, personalised diet plan, correction of poor dietary intake and correction of perception towards healthy eating. We collected data on body mass index (BMI), patient demographics and outcome. RESULTS: 96 percent of the patients were female and 86.2 percent were Chinese. The median BMI at initial consultation was 14.7 kilogramme per square metre (range, 8.6-18.8 kilogramme per square metre). 76 percent were between 13 and 20 years old. 83 percent of the patients came back for follow-up appointments with the dietitians in addition to consultation with the psychiatrist. Overall, there was significant improvement in weight and BMI from an average 37 kg to 41 kg and 14.7 kilogramme per square metre to 16.4 kilogramme per square metre, respectively, between the fi rst and fi nal consultations (p-value is less than 0.001). The average duration of followup was about eight months. Among the patients on follow-up, 68 percent showed improvement with an average weight gain of 6 kg. Patients that improved had more outpatient follow-up sessions with the dietitians (4.2 consultations versus 1.6 consultations; p-value is less than 0.05), lower BMI at presentation (14.2 kilogramme per square metre versus 15.7 kilogramme per square metre; p value is less than 0.01) and shorter duration of disease at presentation (one year versus three years; p-value is less than 0.05) compared with those who did not improve. Seven patients with the disease for more than two years did not show improvement with follow-up. CONCLUSION: We gained valuable understanding of the AN patients referred to our tertiary hospital for treatment, two-thirds of whom improved with adequate follow-up treatment. Patients that had suffered AN longer before seeking help appeared more resistant to improvement. PMID- 17342292 TI - The Bioenteric Intragastric Balloon (BIB) as a treatment for obesity: poor results in Asian patients. AB - INTRODUCTION: The Bioenteric Intragastric Balloon (BIB, Inamed Health, Santa Barbara, CA, USA) is an endoscopic method for achieving restriction of gastric intake in obese patients. It is less invasive and cheaper than bariatric surgery, but can only be left in the stomach for six months. We report our experience with the BIB in Singapore. METHODS: Since its introduction to our hospital in 2004, a prospective database has been kept of all patients undergoing BIB insertion. This database was used to retrieve the information for this study. RESULTS: 20 patients have undergone BIB insertion. Mean patient age was 40 (range, 28-52) years and 85 percent were female. Mean body weight was 79.6 (range, 67.6- 103.7) kg. Mean body mass index (BMI) was 31.5 (range, 27.8-38.8) kilogramme per square metre. Mean excess weight was 21.2 (range, 11.9-37.6) kg. The BIBs were inserted under conscious sedation. BIB intolerance was a major problem and four patients (20 percent) required early BIB removal due to refractive nausea and epigastric discomfort. All remaining BIBs were removed after six months under conscious sedation. The mean maximum weight loss during the six months was 5.9 (range, 1.4 13.4) kg. The mean maximum percentage of excess weight lost was 32.4 (range, 6.7 87). Weight loss was reasonably preserved at the end of the sixmonth period, but by one year, when all the patients had been without BIBs for at least six months, the mean weight loss for the group compared to pre-BIB weight was only 1.5 kg (range, weight gain 5.3 kg to weight loss 9 kg). The mean percentage excess weight loss at one year was 10.9 (range, 15.1 percent weight gain to 31.3 percent weight loss). Only four patients (20 percent) regarded their experience with the BIB as a success. CONCLUSION: The BIB is poorly tolerated by Asian patients, even when lower volumes are inserted into the balloon to compensate for the smaller Asian stature. Although temporary weight loss can be achieved, mandatory removal of the BIB at six months results in regain of the lost weight in the majority of patients. Eligible patients (BMI 32.5 and above) should be encouraged to undergo bariatric surgery rather than BIB to achieve long-term reliable weight loss. Patients who are ineligible for bariatric surgery may benefit from BIB, especially if they have severe comorbidities and have failed to lose weight by any other means in a validated weight management programme, but the chance of long-term success is poor. PMID- 17342293 TI - Comparative evaluation of obesity measures: relationship with blood pressures and hypertension. AB - INTRODUCTION: The purpose of the present study was to compare the relationship of all obesity measures with blood pressures and to fi nd out the best obesity measure, associated with greater risk of hypertension. METHODS: A total of 180 adult Bengalee Hindu men from Hridoypur of 24 Pgs (N), West Bengal, India were evaluated in the present cross-sectional study. Biosocial data (such as age, education, occupation), anthropometry and blood pressure measurements were obtained. Body mass index (BMI), waist hip ratio (WHR), conicity index (CI) and waist stature ratio (WSR) were subsequently derived. Statistical analysis includes linear and logistic regression. RESULTS: The mean age of the studied individuals was 35.7 years (standard deviation, 9.35 years) and the frequency of hypertensive individuals was 11.7 percent. WSR explained 14.3 percent variance of systolic blood pressure (SBP), followed by waist circumference (WC) (13.0 percent) and BMI (13.1 percent). BMI (8.8 percent), WC (8.6 percent) and WSR (8.4 percent) explained closely the same amount of variance of diastolic blood pressure (DBP). All obesity measures were significantly and positively correlated with blood pressures. The odds-ratio (OR) associated with a 1 kilogramme per square metre increase in BMI was 1.17. Comparing values for a 0.1 increase in WSR was 1.22, followed by WHR (OR 1.09). A 1.0 cm increase in WC was associated with OR 1.07 followed by OR 1.06 for a 1.0 increase in CI. In multivariate analysis, significant predictors of hypertension were age and BMI. CONCLUSION: Among all obesity measures, WSR and BMI explained comparatively larger amount of variance of SBP and DBP, respectively. However, the greater risk of developing hypertension was associated with increasing BMI. PMID- 17342294 TI - Immediate food hypersensitivity among adults attending a clinical immunology/allergy centre in Singapore. AB - INTRODUCTION: The patient characteristics, clinical features and causative foods in 74 consecutive adult patients with immediate food hypersensitivity were studied. METHODS: A retrospective review of 74 consecutive adults who presented during the study period from July 1, 1994 to April 30, 2002 was performed. RESULTS: There were 35 male and 39 female patients, with a mean age of 36.3 +/- 10.9 (range, 19-66) years. The most common causative foods were seafood crustaceans, molluscs and bird's nest. Prawn and crab were the most commonly implicated crustacean, and limpet the commonest culprit mollusc. The main symptoms were periorbital angioedema (64.9 percent), dyspnoea/wheezing (44.6 percent) and urticaria (44.6 percent). 66 percent of the patients developed anaphylaxis. 34 (45.9 percent) had concomitant allergic rhinoconjunctivitis, asthma, eczema or combinations of these atopic diseases. Only six (8.1 percent) patients had a family history of food allergy. Skin prick tests (SPT) to commercially-prepared food allergens were positive in 22 of 36 patients (61.1 percent) tested. SPT to the fresh, cooked or canned food products were positive in 11 of 20 (55 percent) cases where the food allergen was not commercially available. Open food challenges were required for diagnosis in two patients who had negative SPT. CONCLUSION: The most common food allergens in our patients were seafood crustaceans, molluscs and bird's nest. More than half of the patients had concomitant allergic rhinitis, asthma and/or eczema. The pattern of food allergy in Singapore differs from Caucasian populations, likely to be because of different regional dietary patterns and methods of food preparation. PMID- 17342295 TI - Comparison of two doses of corticosteroid in epidural steroid injection for lumbar radicular pain. AB - INTRODUCTION: Low back pain and lumbar radicular pain are the leading causes of job loss worldwide. Therapeutic approaches to lumbar radicular pain, including sciatica and spinal canal stenosis, are diverse. Many clinicians use 80 mg long acting glucocorticoids in epidural steroid injections (ESI). The aim of this study is to compare the clinical response of 80 mg versus 40 mg methylprednisolone in ESI. METHODS: 84 patients with newly exacerbated lumbar radicular pain were randomly al located into two groups. 43 patients under went ESI with 80 mg Depo-Medrol and 41 age- and sex-matched cases received 40 mg Depo Medrol as the comparison group. The pain in the second week, and every month thereafter was assessed using a visual analogue scale (VAS). RESULTS: Remarkable improvement in one month VAS occurred in 64 cases (75 percent) from both groups. VAS values between 80 mg and 40 mg groups were comparable in the two-week (p value is 0.827) and three-month (p-value is greater than 0.746) post-injection periods. Slightly better results were shown in patients in the 40 mg group after one month. CONCLUSION: In the case of lumbar radicular pain, ESI with low dose (40 mg) methylprednisolone is as effective as high dose (80 mg) with comparable results and less adverse profile. PMID- 17342296 TI - Does the implementation of radiation oncology outpatient infection control measures adversely affect patient satisfaction with doctor-patient interaction? AB - INTRODUCTION: There are worldwide concerns of an impending avian influenza outbreak, with nations formulating infection control strategies to prepare for such an event. Little evidence exists for how infection control measures impact on the provision of cancer services, or how patient experience would be affected. Our aim was to compare patient satisfaction with doctor-patient interaction, during and following a period of infection control measures. METHODS: We measured patient satisfaction using a validated 29-question instrument for two weeks during the implementation of strict infection control measures as a result of the severe acute respiratory syndrome outbreak (T1), and compared results with a two week period after measures had been lifted (T2). RESULTS: A total of 296 patients were surveyed, 149 at T1 and 147 at T2. Most patients indicated overall satisfaction, with 92.3 percent and 86.9 percent satisfied at T1 and T2, respectively (p-value is not significant). Mean satisfaction index was 3.02 and 3.04 out of 4 at T1 and T2, respectively (p-value is not significant). However, the responses for several individual questions did differ significantly between time points. At T1 more patients indicated satisfaction for understanding the doctor's plans (p-value is 0.001), while at T2, more patients indicated satisfaction for being told how to care for their condition (p-value is 0.04). CONCLUSION: The study demonstrated high patient satisfaction at both time points. Similar levels of satisfaction despite infection control measures may be due to patients being more tolerant of problems in doctor-patient interactions during the outbreak due to media campaigns. This research may facilitate those healthcare services planning to minimise the impact of infection control measures on patient care. PMID- 17342297 TI - Delayed fungal infection following augmentation mammoplasty in an immunocompetent host. AB - We report an unusual case of infection of a breast implant with Trichosporon spp. in an immunocompetent host. There has only been one other reported case in the published literature. The patient was a healthy 27-year-old woman who presented with pain and swelling 17 months after augmentation mammoplasty with a saline implant. Ultrasound-guided aspiration of the effusion surrounding the implant yielded Trichosporon spp. on culture. Oral therapy with fluconazole was commenced, and the implant was salvaged. The nature of this fungi, its mode of transmission and treatment are reviewed. The implications and management of implant infections are also discussed. Physicians should be aware that infection may be delayed, and cultures should be performed for aerobic and anaerobic organisms as well as acid-fast bacilli and fungi. Prompt and appropriate antimicrobial treatment may arrest the infection, sparing the patient the morbidity of a surgical drainage or implant removal. PMID- 17342298 TI - Doubtful descent, dilemma and diagnosis: a case of Kallmann syndrome. AB - A 16-year-old boy with a diagnosis of bilateral cryptorchidism was referred for preoperative evaluation. He had diminished hearing and difficulty in vision since birth, with inattentiveness, poor school performance and delayed milestones. He was previously operated on for cleft lip. General survey revealed bilateral short fourth metacarpals and an operative scar mark over the left nostril and upper lip. He had a micropenis, small soft testes with anosmia, and sensory-motor deafness. The hormonal assay was consistent with hypogonadotrophic hypogonadism. Magnetic resonance imaging of the brain and computed tomography cisternography revealed almost hypoplastic olfactory bulb with an ill-defined olfactory tract and sulci, supporting the clinical diagnosis of Kallmann syndrome. PMID- 17342300 TI - Clinics in diagnostic imaging (114). Rupture of the right testis. AB - A 22-year-old man, who was kicked in the scrotum during Thai kickboxing, presented with a painful swelling of the right hemiscrotum. Scrotal ultrasonography (US) showed an enlarged right testis with heterogeneous echogenicity and irregular contours. Colour Doppler US showed vascularity in the upper pole of the right testis and avascularity in the lower pole. Emergency exploration of the right hemiscrotum revealed laceration of the lower pole of the right testis. Debridement and repair of the right testis were performed. The clinical manifestations, role of US and US findings of scrotal trauma are discussed. PMID- 17342301 TI - Surveillance of antimicrobial susceptibility of urinary pathogens in a tertiary care hospital. PMID- 17342304 TI - Non-invasive screening of lung nodules in mice comparing a novel volumetric computed tomography with a clinical multislice CT. AB - In vivo imaging of small animal models will play an increasingly important role in cancer research, as new imaging systems that employ non-invasive protocols and offer high-resolution capability become available. A flat-panel volumetric computed tomograph (fpvCT) was evaluated to determine if minimally invasive protocols can be used to provide the spatial resolution required for lung imaging in small animals. The detection of small pulmonary nodules in a Lewis carcinoma model was investigated, and fpvCT was compared with a multislice computed tomograph (MSCT). Five C57/BL6 mice with Lewis lung carcinoma were monitored with both modalities over two weeks. Sensitivity of the systems was measured by comparing the results with histology, and the incidence of first visualization of the tumors in the two systems was determined. Compared to MSCT, fpvCT proved its superior sensitivity in detection of lung nodules. Due to its isotropic resolution and a significant reduction of partial volume effects, early detection and reasonable determination of growth in very small tumors was only possible with fpvCT. fpvCT is a high-resolution imaging system that proved its ability to perform in vivo monitoring of a pulmonary lung tumor model in mice. This permits longitudinal investigations in small animals for cancer research. PMID- 17342305 TI - Increased BRCA1 protein in mammary tumours of rats fed marine omega-3 fatty acids. AB - Any factor affecting BRCA gene regulation may be of interest in the prevention of breast tumourigenesis. We studied the influence of dietary docosahexaenoic acid (DHA), a major omega-3 fatty acid present in marine products, on rat autochthonous mammary tumourigenesis. DHA-supplementation significantly reduced the incidence of tumours (30%, P=0.007) and led to a 60% increase (P=0.02) in BRCA1 protein level. Since DHA influences the product of a major tumour suppressor gene, this finding may contribute to the observation that high-fish consumption reduces the risk of breast cancer. PMID- 17342306 TI - Co-expression of gastric and biliary phenotype in pyloric-gland type adenoma of the gallbladder: immunohistochemical analysis of mucin profile and CD10. AB - Pyloric-gland type adenoma of the gallbladder is formed by proliferation of glands resembling pyloric glands, morphologically. No previous report has described the cellular phenotype and differentiation of pyloric-gland type adenoma of the gallbladder, using CD10 as a marker of proper biliary phenotype. Immunostainings were performed for mucin markers such as MUC5AC, human gastric mucin (HGM) for gastric foveolar type epithelium, MUC6, M-GGMC-1 for pyloric gland type and MUC2 for intestinal goblet-cell type, and for CD10 as a proper biliary type marker on 58 pyloric-gland type adenomas of the gallbladder, as well as for p53, Ki-67 and CDX2. The percentage (X) of reactive cells in relation to the total number of tumor cells was estimated semi-quantitatively, and divided into four categories: X=0% (negative), 0%or=30%. CDX2 expression was considered to be positive when the percentage of positively stained cells was >or=10%. Out of the 58 pyloric-gland type adenomas, >or=30% of adenoma cells were positive for MUC5AC in 22 (38%) tumors, HGM in 29 (50%), MUC6 in 58 (100%), M-GGMC-1 in 54 (93%), MUC2 in none (0%), and CD10 in 20 (34%). MUC6 (P<0.001) and M-GGMC-1 (P<0.001) mucins were detected more frequently in pyloric gland type adenomas, and CD10 expression was significantly decreased, compared with normal gallbladder epithelium (P=0.006). P53 overexpression was not found in any of the 58 tumors, including two adenomas with carcinomatous foci. The mean number of Ki-67-positive cells was 10.3+/-5.8%. CDX2 expression was judged as negative in all 58 pyloric-gland type adenomas. In pyloric-gland type adenomas of the gallbladder, expression of pyloric-gland type mucins was observed with a high frequency, whereas intestinal goblet-cell mucins were rarely seen. In addition, co-expression of gastric foveolar type mucins and CD10 was also demonstrated. Pyloric-gland type adenomas of the gallbladder show a differentiation toward pyloric glands in terms of immunohistochemistry, as well as morphology, accompanied by co-expression of gastric foveolar and native biliary phenotypes. PMID- 17342307 TI - Association of extracellular matrix metalloproteinase inducer in endometrial carcinoma with patient outcomes and clinicopathogenesis using monoclonal antibody 12C3. AB - Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin superfamily of adhesion molecules and has a role in the activation of several matrix metalloproteinases (MMPs). We evaluated whether EMMPRIN expression is related to tumor progression and patient outcome in human endometrial carcinoma. Paraffin-embedded surgical tissue samples from 112 patients with endometrial carcinoma were stained with anti-EMMPRIN antibody (monoclonal antibody 12C3:MoAb 12C3) for immunohistochemical analysis. EMMPRIN protein was expressed in cancerous lesions with the incidence of 97.3% (109 of 112 cases), but not in normal lesions. The scores determined by the combination of intensity and pattern of EMMPRIN staining in cancer cells correlated significantly with various histopathological risk factors: advanced stage, P=0.001; poorly differentiated carcinoma, P<0.001; lymph node metastasis, P=0.002; and lymphatic vessel infiltration, P=0.027. More importantly, recurrence free survival was shortened in patients with higher EMMPRIN scores (HR, 3.08; 95% CI, 1.32-7.19; P=0.01). These results suggest that measurement of EMMPRIN expression with simple immunohistochemical staining may enhance the understanding of the pathophysiology of endometrial carcinoma. PMID- 17342308 TI - KL-6 mucin is a useful immunohistochemical marker for cholangiocarcinoma. AB - This study aimed to clarify the clinical significance of the expression of KL-6 mucin, a type of MUC1, in primary liver cancer. Tissue specimens were collected from 21 patients with cholangiocarcinoma (CC), 78 with hepatocellular carcinoma (HCC), and 12 with combined hepatocellular and cholangiocarcinoma (cHCC-CC). Immunohistochemical analysis was done using a monoclonal antibody for KL-6 mucin as well as antibodies for Hep1 or CK7. KL-6 staining was positive in all the CC tissues examined, while it was not positive in any of the HCC tissues. Similar selectivity of KL-6 staining was also observed in the cHCC-CC specimens, and the cholangiocellular tissue could be clearly delineated by KL-6 staining. In contrast, 79.5% of HCC specimens and 25.0% of cHCC-CC specimens were positive for Hep1 in the hepatocellular tissues, while none of the CC or cHCC-CC specimens were positive in the cholangiocellular tissues. Staining for CK7 was positive in 95.2% of CC and 35.9% of HCC specimens, while 58.3 and 25.0% of cHCC-CC specimens displayed positivity for CK7 in the cholangiocellular and hepatocellular tissues, respectively. These results suggest that KL-6 may be a useful tumor marker for distinguishing CC from HCC. In addition, the high selectivity of KL-6 for cholangiocallular tissue may help to provide information for deciding the clinical strategy in cHCC-CC patients. PMID- 17342309 TI - Pelvic recurrence after Miles' operation for anastomotic recurrence in a patient with stage I rectal cancer invading the proper muscle layer: Case report. AB - We performed D2 low anterior resection in a patient with stage I rectal cancer [pathological diagnosis: proper muscle (pm) invasion, n0, lymphatic invasion (ly), (-); venous invasion (v), (-); anal margin, (-)]. The tumor recurred at the anastomotic site approximately one year later and was treated with Miles' operation [pm, n0, ly (+); v (-); deep border of the primary tumor (-)]. The tumor marker CEA increased to 50.4 ng/ml at four months after surgery and pelvic local recurrence was detected. Since then, the patient has been receiving chemoradiotherapy on an out-patient basis. Cytokeratin immunostaining of all the lymph nodes collected during the two operations showed clusters of occult neoplastic cells (ONCs) in the perinodal fat around the nodes harvested at the first operation. These findings suggest that the risk of local recurrence of rectal cancer is increased even in stage I disease if ONCs are found in the perinodal fat. Further studies are required to examine the relationship between local recurrence and extranodal ONCs in patients with primary rectal cancer. PMID- 17342310 TI - Analysis of gene expression in different stages of MeIQx-induced rat hepatocarcinogenesis. AB - To clarify hepatocarcinogenesis by the heterocyclic amine, 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx), we investigated the global expression of genes in rat liver. Rats were continuously fed MeIQx 100 ppm in their diet, and were sacrificed at weeks 4 and 16 for early time points, and week 104 for tumor sampling. Global expression analysis using oligonucleotide microarrays (Affimetrix Gene Chip, Rat Genome 230 2.0 Array) was carried out to detect altered genes in MeIQx-treated liver at 4 and 16 weeks (n=5, each), MeIQx-induced hepatocellular adenomas (HCA; n=3), and hepatocellular carcinomas (HCC; n=3), compared with age-matched normal livers (n=5). To investigate functional networks and gene ontology, two clusters were analyzed by Ingenuity Pathway Analysis. Clustering analysis of global genes demonstrated gene profiles of HCA and HCC to greatly differ from those of age-matched normal liver. However, after treatment with MeIQx for 4 or 16 weeks, no major differences were apparent. Ingenuity Pathway Analysis suggested pathways related to the cell cycle and glutathione metabolism may be involved in MeIQx-induced hepatocarcinogenesis. Real-time PCR analysis confirmed elevation of cyclin B1, cell division cycle 2, glutathione peroxidase 2 and glutathione S-transferase A2 in tumors, but not in early stage livers. In conclusion, molecular signatures of MeIQx-induced tumors clearly vary from that of age-matched normal liver, but no such shift is evident at early stages of hepatocarcinogenesis. PMID- 17342311 TI - Dysregulated expression of HOX and ParaHOX genes in human esophageal squamous cell carcinoma. AB - Homeobox genes function as master regulators in embryonic morphogenesis. We hypothesized that homeobox genes are essential to maintain tissue- or organ specificity even in adult body and that the dysregulated expression of homeobox genes results in tumor development and progression. To better understand the roles of homeobox genes in development and progression of esophageal cancer, we analyzed the expression patterns of 39 HOX genes and 4 ParaHOX (CDX1, CDX2, CDX4 and PDX1) genes in esophageal squamous cell carcinoma (ESCC) and normal esophageal mucosa tissues. A total of 48 primary ESCC tissues and 7 normal esophageal mucosa tissues were resected from patients who underwent radical surgery without any preoperative chemotherapy or radiotherapy. The expression of HOX and ParaHOX genes were analyzed by a quantitative real-time RT-PCR method and immunohistochemistry. The expression levels of 24 HOX genes, CDX1, CDX2 and PDX1 were significantly higher in ESCC compared to normal mucosa (p<0.01, Mann-Whitney U test). The Immunohistochemical study revealed that HOXA5 and D9 proteins were more cytoplasmic in ESCC than normal mucosa cells. Our data indicate that the disordered expression of HOX and ParaHOX genes are involved in the development of ESCC or its malignancy. PMID- 17342312 TI - Low concentrations of the histone deacetylase inhibitor, depsipeptide, enhance the effects of gemcitabine and docetaxel in hormone refractory prostate cancer cells. AB - Histone deacetylase inhibitors (HDACis) have been developed as a new type of drug for cancer treatment. In this study, we examine the augmentation efficacy of depsipeptide (FK228) in combination with gemcitabine (GEM) or docetaxel (DOC) in vitro and in vivo against hormone refractory prostate cancer (HRPC). The anti proliferative effects, cell cycle distribution and apoptotic status were assessed in HRPC DU145 cells treated with these agents. The in vivo anti-tumor effects of the combination therapy with FK228 and GEM were further evaluated in the DU145 xenografts. FK228 induced a substantial acetylation of the histone proteins even at a low concentration of IC20 (0.56 ng/ml for 48 h treatment), while no effects on the cell cycle arrest and apoptosis induction were observed at the low concentration level. The pretreatment of cells with the IC20 dose of FK228 enhanced the cytotoxicity of both chemotherapeutic agents although the augmentation was more profoundly observed in GEM than DOC. The effects of the FK228 pretreatment were also observed in the in vivo experiment. The mean tumor doubling-time in the FK228 pretreatment combined with GEM was two times longer than that of the monotherapy with FK228 or GEM (p<0.001). These results show that pretreatment with low-dose FK228 enhances the chemosensitivity of DU145 tumors to GEM in vivo, suggesting the therapeutic potential of a new combination of HDACis and conventional chemotherapeutic agents. Further studies are required in order to assess the efficacy of this combination regimen in HRPCs in general. PMID- 17342313 TI - Bax gene therapy for human osteosarcoma using cationic liposomes in vivo. AB - The purpose of this study was to evaluate the anti-tumor effect of human osteosarcoma (HOSM-1) tumor xenografts in nude mice via transfer of the Bax gene using cationic liposomes. The HOSM-1 tumors transplanted into nude mice grew to 5 6 mm in diameter. Following growth of the tumor to this size, liposomes with the Bax plasmid were applied locally to the peripheral tumor (day 0) and were applied 3 times per week for 2 weeks (6 times in total). The tumor growth inhibitory effect was evaluated by measuring the tumor volume up to day 40. The expression of Bax was observed by immunohistochemical analysis and apoptosis was detected using the TUNEL assay. Tumor growth increased only slightly during the administration period, and tumor volume on day 50 was 43% of that in the saline control group. In the tumor margin 48 h after the completion of administration, Bax immunoreactivity was detected and apoptotic cells were clearly increased. Since these results suggested that Bax gene therapy using cationic liposome induced apoptosis in HOSM-1 tumor in vivo, we anticipate that this therapy will be useful for the treatment of osteosarcoma. PMID- 17342314 TI - Loss of L-PHA-, PNA-, or ConA-reactive oligosaccharides is associated with a poor prognosis in human Burkitt's lymphoma. AB - The expression of cell surface oligosaccharides is associated with various biological phenomena. To clarify the relationship between lectin binding and the survival of patients with Burkitt's lymphoma, tumor samples from nine patients with Burkitt's lymphoma were analyzed by lectin histochemistry. Kaplan-Meier analysis showed that survival is significantly shorter for patients with negative reactivity for lectins from Phaseolus vulgaris (L-PHA), Arachis hypogaea (PNA), or Canavalia ensiformis (ConA) than for those with positive reactivity for these lectins. Immunohistochemistry for N-acetylglucosaminyltransferase V, which synthesizes beta1,6-branched oligosaccharides such as L-PHA-reactive oligosaccharides, was positive in 8 of 9 patients, but there was no correlation between its expression and that of L-PHA-reactive oligosaccharides. Collectively, a loss of L-PHA-, PNA-, or ConA-reactive oligosaccharides is closely associated with a poor prognosis in patients with Burkitt's lymphoma. PMID- 17342315 TI - Growth inhibition of colon cancer cells by transfection of dominant-negative apoptosis signal-regulating kinase-1. AB - Apoptosis signal-regulating kinase-1 (ASK-1) is an important molecule for the pro apoptotic signaling. ASK-1 also contributes to the cellular survival for many types of cells. Thus, ASK-1 has a broad range of biological activities depending on the cell type. The present study assessed the role(s) of ASK-1 in colorectal cancer cells (HT-29) by using adenovirus vectors expressing wild-type (WT)-ASK-1 or dominant-negative (DN) mutant of ASK-1 and recombinant adenovirus containing the bacterial beta-galactosidase gene (Ad-LacZ), a negative control for Ad-DN-ASK 1. Selective phosphorylation of ASK-1 at Thr 845, a kinase domain site, but not Ser 83 nor 967 sites was induced by serum stimulation in a time-dependent manner. Transfection with Ad-DN-ASK-1 inhibited the serum-induced phosphorylation of p38 mitogen-activated protein kinase, a downstream molecule of ASK-1. Transfection with Ad-DN-ASK-1 diminished the serum-induced cell proliferation in a dose dependent manner, whereas WT-ASK-1 increased it. Apoptosis assessed by Hoechst staining was induced in the Ad-DN-ASK-1 treated cells. In vivo transfection of Ad DN-ASK-1 into tumor xenografts of HT-29 cells in nude mice significantly decreased the tumor volume on day 29. Cleaved caspase-3 was found in the tumors of DN-ASK-1 treated mice. We obtained the first evidence that DN-ASK-1 transfection exerted significant antitumor effects on colon cancer mediated by apoptosis. PMID- 17342316 TI - Novel cell-surface peptides specific to human oral squamous cell carcinoma using an E. coli peptide display library. AB - We attempted to find a specific antigen of oral squamous cell carcinoma (SCC) cells that could be safely applied to gene therapy in the conservative clinical treatment of oral cancer. We performed subtraction using normal human keratinocyte cells, followed by selection using four oral SCC cell lines. We isolated three clones from poorly differentiated SCC cells and four from well differentiated SCC cells. These seven clones adsorbed to the oral SCC cells at rates 10-100 times those of normal human keratinocyte cells. The three clones from the poorly differentiated SCC cells showed the same peptide sequence (LAPRTHP). Of the four clones from the well-differentiated SCC cells, three showed the same peptide sequence (FGTLPGT) and the fourth showed a different one (VTPNSTP). Each peptide sequence may recognize the material that exists specifically on the oral SCC cell cortex. We can expect applications not only for tumor-targeting treatment using a gene therapy virus vector but also for diagnosis using, as a tumor marker, the peculiar SCC surface material that these peptides recognize. PMID- 17342317 TI - Inhibition of hypoxia-induced angiogenesis by sodium butyrate, a histone deacetylase inhibitor, through hypoxia-inducible factor-1alpha suppression. AB - Hypoxia-inducible factor-1 (HIF-1) plays a pivotal role in cellular response to low oxygen concentration, such as angiogenesis in tumors. Here, we found that a histone deacetylase inhibitor, sodium butyrate, inhibits the hypoxia-induced induction and activity of HIF-1alpha in HT1080 human fibrosarcoma cells. Moreover, sodium butyrate also suppressed the hypoxia-stimulated angiogenic effects and downregulated HIF-1alpha and vascular endothelial growth factor expression in vascular endothelial cells. These findings suggest that sodium butyrate may play important roles in tumor suppression via inhibition of HIF 1alpha mediated angiogenesis under hypoxic conditions. PMID- 17342318 TI - Diagnostic utility of dual fusion PML/RARalpha translocation DNA probe (D-FISH) in acute promyelocytic leukemia. AB - Translocation(15;17) leading to the formation of fusion gene PML/RARalpha is the diagnostic hallmark of acute promyelocytic leukemia (APL). Interphase fluorescence in situ hybridization (FISH) is one of the diagnostic tools employed for the detection of PML/RARalpha rearrangement. Using a dual color dual fusion (D-FISH) PML/RARalpha translocation DNA probe which hybridises both to PML/RARalpha and RARalpha/PML fusion genes, we characterised the FISH pattern of 52 APL patients at diagnosis and correlated the findings with conventional cytogenetics and RT-PCR analysis. The diagnostic sensitivity of the probe for PML/RARalpha was 100%. Seven patients had atypical D-FISH patterns; two had a masked PML/RARalpha fusion signal caused by the insertion of PML into RARalpha on 17q; 3 had an extra copy of PML/RARalpha in the form of isochromosome der(17)(q10)t(15;17) and one had duplication of the normal RARalpha gene with an ider(17q) masquerading as i(17)(q10). There was also one case of t(7;17;15) with a typical D-FISH pattern and in which metaphase FISH suggested an unusual 4-point break. In summary, PML/RARalpha D-FISH is a highly sensitive method for confirming diagnosis of APL. However D-FISH cannot be solely relied on for the diagnosis of APL owing to atypical patterns which are infrequently observed in cases with additional 17q structural abnormalities, gene insertion and gene duplication. PMID- 17342319 TI - Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells. AB - Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer. PMID- 17342320 TI - Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion (review). AB - The medicinal properties of extracts from the hemp plant Cannabis sativa have been known for centuries but only in the 90s membrane receptors for the Cannabis major principle were discovered in mammalian cells. Later on the endogenous ligands for the cannabinoid receptors were identified and the term 'endocannabinoid system' was coined to indicate the complex signaling system of cannabinoid receptors, endogenous ligands and the enzymes responsible for their biosynthesis and inactivation. The 'endocannabinoid system' is involved in a broad range of functions and in a growing number of pathological conditions. There is increasing evidence that endocannabinoids are able to inhibit cancer cell growth in culture as well as in animal models. Most work has focused on the role of endocannabinoids in regulating tumor cell growth and apoptosis and ongoing research is addressed to further dissect the precise mechanisms of cannabinoid antitumor action. However, endocannabinoids are now emerging as suppressors of angiogenesis and tumor spreading since they have been reported to inhibit angiogenesis, cell migration and metastasis in different types of cancer, pointing to a potential role of the endocannabinoid system as a target for a therapeutic approach of such malignant diseases. The potential use of cannabinoids to retard tumor growth and spreading is even more appealing considering that they show a good safety profile, regarding toxicity, and are already used in cancer patients as palliatives to stimulate appetite and to prevent devastating effects such as nausea, vomiting and pain. PMID- 17342321 TI - Silencing of O6-methylguanine DNA methyltransferase in the absence of promoter hypermethylation in hepatocellular carcinomas from Australia and South Africa. AB - The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is involved in cellular defences against alkylating agents. Alterations in the MGMT gene may result in an increase in the mutation rate and risk of malignant transformation. We have previously shown that MGMT is implicated in colorectal carcinogenesis particularly in cancers which display microsatellite instability, a marker of impaired DNA repair. The aims of the current study were to assess the roles of MGMT and microsatellite instability in hepatocellular carcinomas (HCCs) from Australia and South Africa. DNA was extracted from malignant and non-malignant liver tissue from 37 Australian and 24 South African patients, and histologically normal liver from 20 transplant donors. MGMT promoter hypermethylation and MGMT protein expression were assessed using methylation specific PCR and immunohistochemistry. Microsatellite instability was examined using a panel of 23 microsatellite markers previously used to detect allelic imbalance and two specific markers for the detection of low levels of microsatellite instability. Methylation specific PCR did not detect any methylation of the MGMT promoter in Australian and South African HCCs. Similarly, no hypermethylation of MGMT was observed in the adjacent non-malignant liver or histologically normal liver. MGMT staining was predominantly nuclear with some cytoplasmic staining. Overexpression of MGMT protein was detected in 14 (39%) HCCs, while a reduction in protein expression was evident in 14 (39%) HCCs. In the remaining 8 cases the expression of MGMT was comparable in HCCs and adjacent non-malignant tissue. Interestingly, MGMT expression decreased relative to adjacent non-malignant liver tissue in patients who had aetiologies other than viral hepatitis for their underlying liver diseases (p<0.02). No microsatellite instability was detected in this series of 61 HCCs. This suggests that epigenetic silencing of MGMT and microsatellite instability does not play an important role in this series of HCCs derived from different populations. PMID- 17342322 TI - Failure of apoptosis and activation on NFkappaB by celecoxib and aspirin in lung cancer cell lines. AB - Recent studies have demonstrated that antineoplastic activity of Cox-2 inhibitors may depend on targets other than Cox: among those, nuclear factor kappaB (NFkappaB) seems the most promising. Although preclinical studies have suggested that aspirin and Cox-2 inhibitors may influence the progression of lung cancer, the molecular mechanisms of these protective effects in this tumor type has not been fully elucidated. We investigated the effects of celecoxib and aspirin in the induction of apoptosis and in the ability to activate NFkappaB in three non small cell lung cancer cell lines. Apoptosis was evaluated by FACS, caspase activation assay and expression of apoptosis-related genes by RT-PCR, while NFkappaB activation was assessed by immunofluorescence. No apoptotic response was observed after treatment with both high and low dose of celecoxib. Nevertheless, celecoxib at both concentrations induced a strong NFkappaB activation, with increased expression of NFkappaB-dependent genes, such as bcl-2, bcl-XL and survivin. Similarly, aspirin at both concentrations did not induce any apoptotic response, but activated NFkappaB in a dose-dependent manner. This study supports the hypothesis that NFkappaB activation is an important effect of NSAIDs in lung cancer, leading to apoptosis resistance. This effect of both aspirin and celecoxib may be considered undesirable in lung cancer chemoprevention. PMID- 17342323 TI - Stomatin-like protein 2 is overexpressed and related to cell growth in human endometrial adenocarcinoma. AB - Stomatin-like protein 2 (SLP-2) is a novel and unusual stomatin homologue of unknown functions. It was first identified to be overexpressed and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma. We show herein the involvement of SLP-2 in human endometrial adenocarcinoma, and the effects of SLP-2 on endometrial adenocarcinoma cell growth. The expression of SLP-2 was evaluated in human endometrial adenocarcinoma by semi-quantitative RT-PCR, Westernblotting and immunohistochemistry. Sense and antisense SLP-2 eukaryotic expression plasmids were transfected into the human endometrial adenocarcinoma cell line HEC-1B. MTT assay and flow cytometry assay were performed to investigate the roles of the SLP-2 gene. SLP-2 was overexpressed in endometrial adenocarcinoma compared with their normal counterparts (P2.5 mm than in those with tumors <1.0 mm, and higher frequency was found in nodular melanoma than in the other tumor types. GSTP1 GG genotype was more often found in the patients with brown and mixed eye color or brown and black hair than those with blue and green eyes or blond hair. It is unlikely that polymorphisms of GSTM1, GSTT1 and GSTP1 are general risk factors for melanoma in the Swedish population. GSTM1 null genotype was correlated with Breslow thickness and tumor type, which might serve as an additional biomarker for a rapid tumor progression. GSTP1 GG increases risk for melanoma in the subgroup of individuals with dark eyes or hair. PMID- 17342329 TI - Telomerase activity in peripheral blood mononuclear cells after whole body irradiation. AB - Telomerase activity in vitro represents a radiation-inducible function. To test this effect after irradiation in vivo, we measured telomerase activity in peripheral blood mononuclear cells (PBMC) of 25 patients with leukemia or lymphoma before and 1 h after whole body irradiation. Telomerase activity of the patients was compared to telomerase activity in PBMC of 15 healthy volunteers. Peripheral blood of the patients was taken before and 1 h after the first fraction of whole body irradiation (2 Gy). Blood samples of the volunteers were irradiated ex vivo with 2 Gy. After Ficoll-Paque density gradient centrifugation telomerase activity of 10(4) PBMC per sample was measured using the telomerase PCR ELISA method. No age-dependence of telomerase activity was detected for both the volunteer and the patient group. Telomerase activity in patients was not statistically significantly increased compared to healthy individuals, and this parameter was also no prognostic factor for patient survival. After whole body irradiation an induction of telomerase activity was observed for only 7 patients (28%), or in PBMC of 2 volunteers (13%), respectively. In patients with radiation inducible telomerase activity, a slightly better survival was indicated, but this difference did not reach statistical significance. The feasibility to assess in vivo radiation-induction of telomerase activity in PBMC of leukemia or lymphoma patients was demonstrated. An unexpectedly low number of whole body irradiated patients displayed this phenotype, and the treatment impact of telomerase upregulation in PBMC upon radiation exposure needs to be further analyzed. PMID- 17342330 TI - Differential regulation of DEC2 among hypoxia-inducible genes in endometrial carcinomas. AB - In this study, we demonstrate an important role of activation of the hypoxia inducible factor-1 (HIF-1) pathway in endometrial carcinogenesis and tumor phenotype development of endometrial carcinoma, and suggest a unique role of the HIF-1-target gene, differentiated embryo chondrocyte 2 (DEC2), in carcinogenesis. Hypoxia caused an increase in HIF-1alpha protein expression in 4 endometrial carcinoma cell lines. The expressions of its 5 target genes - DEC1, DEC2, carbonic anhydrase-9 (CA9), vascular endothelial growth factor (VEGF), and solute carrier family 2, member 1 (SLC2A1) - also reactively increased in most of the cell lines, except for DEC2 in the SNG-M cells. The expression levels of DEC2, CA9, and SLC2A1 were significantly higher in the 4 atypical hyperplasia tissues and 82 endometrial carcinomas compared with those in the 21 normal endometria. Clinicopathological analyses of carcinoma patients revealed a significant correlation of the VEGF and SLC2A1 expression with the status of lymph-vascular involvement and lymph node metastasis. The expression levels of CA9 and VEGF were significantly higher in the tumors of post- as opposed to pre-menopausal patients. The SLC2A1 expression was also related to the FIGO stage, but the DEC2 expression was inversely related to the FIGO grade. The activation of the HIF-1 pathway could be related to endometrial carcinogenesis, and the component, DEC2, could have different expression-regulatory mechanisms and unique roles in carcinogenesis. PMID- 17342331 TI - Chemopreventive effect of fermented brown rice and rice bran on 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats. AB - The preventive effects of the dietary administration of brown rice and rice bran fermented with Aspergillus oryzae (FBRA) on oral carcinogenesis induced by 4 nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. At 7 weeks of age, the animals were given 20 ppm 4-NQO in their drinking water for 8 weeks to induce tongue neoplasms. Groups of rats were fed diets containing 5 or 10% FBRA during the initiation or postinitiation phases of the 4-NQO-induced oral carcinogenesis. The other groups consisted of rats fed 10% FBRA or untreated rats. At the termination of the study (week 32), the incidences, multiplicities of tongue lesions (pre-neoplasms and neoplasms) and the cell proliferation activity estimated by the 5-bromodeoxyuridine (BrdU)-labeling index were compared among the groups. Feeding of 5% FBRA during the initiation phase significantly decreased the incidence (68.2 vs 36.8%; p<0.05) and multiplicity (1.05+/-0.84 vs 0.37+/-0.50; p<0.005) of the tongue carcinoma. When feeding of 10% FBRA occurred after the 4-NQO exposure, the multiplicity of tongue carcinoma was also reduced (1.05+/-0.84 vs 0.52+/-0.60; p<0.05). In addition, the dietary administration of FBRA at both doses significantly decreased the BrdU-labeling index in the oral squamous epithelium (p<0.05). Although a dose-dependent response was not observed, FBRA is effective in suppressing the development of 4-NQO-induced oral carcinogenesis by its concurrent exposure to the carcinogen. The inhibitory effect could be related to the suppression of the hyperproliferation of cells in the tongue epithelium and the radical scavenging activity of FBRA. PMID- 17342332 TI - The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo. AB - The epidermal growth factor receptor (EGFR) is a member of the EGFR family of receptors. EGFR and other members of the EGFR family have been shown to play significant roles in human cancer cell proliferation and therefore present important molecular targets for the treatment of cancer. The purpose of this study was to examine the effect of the pan-erbB tyrosine kinase inhibitor CI-1033 against esophageal squamous cell carcinoma in vitro and in vivo. We selected 4 human esophageal squamous cell carcinoma cell lines (TT, TE2, TE6, and TE10), and determined their expression of EGFR and HER2. We examined the ability of CI-1033 to inhibit cell growth in vitro and in vivo. EGFR and HER2 were overexpressed in all 4 esophageal cancer cells. We found that CI-1033 could inhibit the growth of esophageal cancer cell lines in a dose-dependent manner with the inhibition of phosphorylation of both MAPK and AKT. The oral administration of CI-1033 exerted a significant antitumor effect on esophageal cancer tumors in athymic nude mice. Our results suggest that CI-1033 effectively inhibits the growth of esophageal squamous cell carcinoma which co-expresses both EGFR and HER2 with the inhibition of phosphorylation of both MAPK and AKT. Furthermore, in vivo animal studies of CI-1033 suggest that CI-1033 holds significant clinical potential in esophageal cancer. PMID- 17342333 TI - Preparation of fully activated dendritic cells capable of priming tumor-specific cytotoxic T lymphocytes in patients with metastatic cancer using penicillin killed streptococcus pyogenes (OK432) and anti-CD40 antibody. AB - In order to achieve sufficient therapeutic potency, it has been proposed that vaccine therapy with dendritic cells needs to be combined with manipulation of immunological checkpoints, such as inhibition of regulatory T cells and blockade of negative signals, and enhancement of T cell trafficking to tumor sites. In the combinatorial cancer immunotherapy, use of matured/activated dendritic cells (DCs) with more potent antigen presenting capacity seems to be essential for eliciting anti-tumor immune responses. We herein established an ex vivo induction strategy for activated DCs capable of eliciting efficient tumor antigen-specific cytotoxic T lymphocytes (CTLs) from patients with metastatic cancer as well as healthy donors. Immature DCs were matured by 48-h culture in the presence of anti CD40 antibody and penicillin-killed streptococcus pyogenes (OK432). Supplementation with both anti-CD40 and OK432 resulted in induction of activated DCs with higher surface expression of CD80, CD83, CD86 and major histocompatibility complex class II antigens, compared with other mature DCs that were induced by the combination of anti-CD40 with tumor necrosis factor-alpha or lipopolysaccharide. In analysis of the produced cytokine profiles, the activated DCs produced the highest T-helper 1-type cytokines for at least 72 h. Furthermore, the activated DCs, pulsed with tumor-associated antigen peptide, elicited in vitro tumor-specific CTLs, but DCs activated with other combinations did not in cancer patients. Therefore, we suggest that the activated DCs studied here might be used as a basic element for the combinatorial cancer immunotherapy. PMID- 17342334 TI - Expression of Wnt5A and Wnt10B in non-immortalized breast cancer cells. AB - Wnt signaling is usually divided into two pathways: the 'canonical', acting through beta-catenin, and the 'non-canonical' acting through the Ca2+ and planar cell polarity pathway. Both pathways have been implicated in different types of cancer. Most results obtained with established cell lines have been contradictory. Here, we have investigated the expression of Wnt10B (canonical) and Wnt5A (non-canonical) in a panel of finite life-span and established normal and breast cancer cells using quantitative RT-PCR. It was found that there were both significant overexpression of Wnt5A and underexpression of Wnt10B in the metastasis-derived finite life-span breast cancer cells when they were compared to the finite life-span normal and established normal and breast tumor cells. Since expression profiles of primary breast cancer cultures are closer to the original tumor than the established cell lines, future research in this area should take into consideration these differences. PMID- 17342335 TI - Combinatorial prevention of carcinogenic risk in a model for familial colon cancer. AB - Germ line mutations in the tumor suppressor adenomatous polyposis coli (APC) gene, predispose for the clinical familial adenomatous polyposis (FAP) syndrome, a high risk precursor for early onset colon cancer. Similar mutations in the murine homolog of the APC gene, however, produce adenomas predominantly in the small intestine, rather than in the colon. The objectives of the present study were: i) to develop a preclinical cell culture model for human FAP syndrome and ii) to validate this model as a rapid mechanism-based approach for evaluation of the preventive efficacy of combinations of synthetic pharmacological agents or naturally-occurring phytochemicals, for the risk of colon carcinogenesis. The clonally selected 850Min COL-Cl1 cell line derived from histologically normal colon of ApcMin/+ mouse exhibited aberrant proliferation (64.7% decrease in population doubling time, 820% increase in saturation density, and 81.4% decrease in spontaneous apoptosis), relative to that observed in the colon epithelial cell line C57 COL established from Apc [+/+] C57BL/6J mouse. In addition, unlike the Apc [+/+] C57 COL cells, the Apc mutant cells exhibited enhanced risk for spontaneous carcinogenic transformation as evidenced by 100% increase in anchorage-independent colony formation (C57 COL: 0/12; 850Min COL-Cl1: 12/12, mean colony number 23.6+/-2.7). Treatment of Apc mutant cells with low dose combination of select mechanistically distinct synthetic chemopreventive agents such as celecoxib (CLX) + difluoro methylornithine (DFMO), or naturally-occurring epigallocatechin gallate (EGCG) + curcumin (CUR) produced 160-400% and 220-430% decrease in the viable cell number respectively, relative to these agents used independently. Furthermore, relative to independent agents, CLX+DFMO and EGCG+CUR combinations produced 31.5-82.1% and 45.9-105.4% greater reduction in the number of anchorage-independent colonies. Thus, aberrant proliferation and increased risk for carcinogenesis in the Apc mutant cells, and their susceptibility to low dose combinations of mechanistically distinct chemopreventive agents validate a rapid approach to prioritize efficacious combinations for long-term animal studies and future clinical trials on prevention of colon cancer. PMID- 17342336 TI - Diagnostic accuracy of mammography, ultrasonography and magnetic resonance imaging in the detection of intraductal spread of breast cancer following neoadjuvant chemotherapy. AB - The purpose of this study is to evaluate the accuracy of mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging for the diagnosis of intraductal spread of breast cancer following preoperative neoadjuvant chemotherapy. We evaluated a total of 168 areas of normal breast tissue outside the mass in 42 consecutive female patients with breast cancer using each imaging modality both before and after neoadjuvant chemotherapy. Neoadjuvant chemotherapy comprised two to four cycles of adriamycin-based CAF regimen. Multivariate analysis indicated that calcification on mammography and size of hypoechoic structures on ultrasonography prior to neoadjuvant chemotherapy shows a correlation with intraductal spread on pathologic study. Our study reveals that mammography and ultrasonography are useful in avoiding residual cancer cells caused by intraductal spread following conservative breast surgery. PMID- 17342337 TI - A novel chenodeoxycholic derivative HS-1200 enhances radiation-induced apoptosis in MCF-7 cells. AB - HS-1200, a synthetic chenodeoxycholic acid derivative, has cytotoxic activity in various human cancer cells. The present study was undertaken to examine whether HS-1200 sensitizes radiation-induced apoptosis in MCF-7 human breast carcinoma cells. Clonogenic assay elucidated that the combination treatment with HS-1200 and radiation induced more cytotoxic effects than the radiation treatment alone. Nuclear staining, DNA electrophoresis and Western blot analysis for poly(ADP ribose) polymerase revealed that the increased cytotoxic effect by the combination treatment resulted from the augmentation of apoptosis. There was an increase in the expression level of Bax and its translocation onto the mitochondria, a reduction in the mitochondrial membrane potential in the earlier time-points, and the release of cytochrome c into the cytosol increased in the MCF-7 cells treated with radiation and HS-1200 compared to the cells treated only with radiation. Therefore, the synthetic bile acid derivative, HS-1200, could have the therapeutic potential as a radiosensitizer in MCF-7 cells. PMID- 17342338 TI - E-cadherin mRNA expression analysis in evaluating the natural history of urothelial bladder cell carcinoma: results from a long-term follow-up study. AB - Many studies have indicated that the E-cadherin (E-CAD) expression loss is associated with the loss of cellular differentiation and increased cellular invasiveness and can be correlated with poor prognosis in urothelial carcinoma (UC) of the urinary bladder. The aim of this study was to define the role of E CAD mRNA expression on recurrence, progression and survival in UC of the urinary bladder over a long follow-up period. From 30 patients with bladder UC, enrolled in our previous study, 27 were selected for this study. All patients were re analyzed in terms of clinical and tumor characteristics, tumor pathological analysis and tumor E-CAD mRNA expression. The data were correlated to 12-year follow-up results. Significant correlations between stage (p=0.002), grade (p=0.008) and E-CAD mRNA expression were reported. E-CAD did not show any correlation in predicting recurrence or progression in bladder UC. The survival analysis demonstrated a significant relationship (p=0.019) between patients with expressed E-CAD mRNA levels and cancer-specific survival. Multivariate analysis demonstrated that expression of E-CAD mRNA levels is an independent prognostic factor in terms of cancer-specific survival in UC of the urinary bladder (p=0.002). Our study is the first to demonstrate that mRNA extraction and Northen blot analysis is to be considered a reliable method to evaluate E-CAD mRNA levels for predicting survival rate in patients affected by urothelial bladder cancers. We stress that a long follow-up period is needed to evaluate the role of molecular factors in predicting prognosis in patients affected by bladder UC. PMID- 17342339 TI - Molecular analyses and prognostic relevance of HPV in head and neck tumours. AB - HPV involvement in head and neck (HN) cancer is still under active investigation. Fresh frozen and archival clinical samples from 115 patients affected by HN carcinomas were analysed by PCR-based methods and direct sequencing. HPV types, intra-type variants, physical status, viral load and viral transcript presence were determined. HPV positivity was correlated with the main clinical pathological features, including smoker and drinker status, and the clinical outcome. Twenty-one tumours were HPV positive (18.3%) with HPV16 being the most frequent type (n=14) followed by HPV6 (n=4), HPV33, HPV35, and HPV58 (n=1, each type). Tonsil carcinomas contained more high-risk HPV types (6/8; 75%) than all other sites (p=0.0004). HPV16 genome was integrated in all analysed tumours, as pure integrated form or mixed with concomitant episomal forms (4 cases). The viral load showed a wide variability (range, 0.7-485 copies per cell) with the highest value detected in a larynx tumour and the lowest one in a case of cancer of the oral cavity. In 9 HPV-positive samples where mRNA was available, transcripts of viral early oncogenes originating by integrated, episomal or mixed forms of the viral genome were found. A statistically significant correlation was evidenced between HPV and tumour differentiation, being the virus more associated with tumour grade G3/G4. Multivariate Cox regression analysis revealed that lymph node and grade status were significant independent factors for a worse disease free survival and overall survival, whereas the HPV status was associated with a better overall survival (OR, 0.33; 95% CI, 0.13-0.81; p=0.01). Taken together these results indicate that distinct pathological mechanisms for the malignant transformation in each single HN subsite should be taken in account; HPV molecular analyses should be considered a valid tool to distinguish subsets of oropharyngeal tumours and HPV presence could be useful for the prognostic assessment of HNSCC. PMID- 17342340 TI - The inhibition of proliferation and migration of glioma spheroids exposed to temozolomide is less than additive if combined with irradiation. AB - The aim of this study was to investigate the effect of temozolomide (TZM) in combination with X-rays on proliferation and migration in human glioma spheroids. Multicellular spheroids were derived from GaMg and U87 cell lines. Spheroids were treated with various concentrations of TZM (5 micromol, 0.025 mmol, 0.05 mmol) and irradiation (RT). Proliferation and migration assays were performed. For GaMg spheroids, the proliferation inhibition was 30% (RT), 71%, 79%, 85% (for various TZM concentrations) and 78%, 83%, 90% following RT+TZM. For U87 spheroids, the inhibition of proliferation was 52% (RT), 62%, 78%, 88% (TZM), and 73%, 87%, 92% (RT+TZM). Inhibition of migration for GaMg was 30% (RT), 37%, 63%, 78% (TZM), and 56%, 75%, 84% (RT+TZM). For U87, migration inhibition was 29% (RT), 48%, 52%, 67% (TZM), and 62%, 67%, 73% (RT+TZM). Radiotherapy enhancement ratio (RER) of GaMg/U87 spheroid proliferation was 1.4/1.7 (5 micromol TZM), 1.3/1.8 (0.025 mmol TZM), and 1.4/1.4 (0.05 mmol TZM). RER for migration of GaMg/U87 was 2.2/1.9 (5 micromol TZM), 1.7/1.8 (0.025 mmol TZM), and 1.5/1.4 (0.05 mmol TZM). In terms of inhibition of proliferation and migration, irradiation can lead to an enhancement of the TZM effect in human glioma spheroids, which is less than additive. PMID- 17342341 TI - Effects of MT1 melatonin receptor overexpression on the aromatase-suppressive effect of melatonin in MCF-7 human breast cancer cells. AB - A major mechanism through which melatonin reduces the development of breast cancer is based on its anti-estrogenic actions by interfering at different levels with the estrogen-signalling pathways. Melatonin inhibits both aromatase activity and expression in vitro (MCF-7 cells) as well as in vivo, thus behaving as a selective estrogen enzyme modulator. The objective of this study was to study the effect of MT1 melatonin receptor overexpression in MCF-7 breast cancer cells on the aromatase-suppressive effects of melatonin. Transfection of the MT1 melatonin receptor in MCF-7 cells significantly decreased aromatase activity of the cells and MT1-transfected cells showed a level of aromatase activity that was 50% of vector-transfected MCF-7 cells. The proliferation of estrogen-sensitive MCF-7 cells in an estradiol-free media but in the presence of testosterone (an indirect measure of aromatase activity) was strongly inhibited by melatonin in those cells overexpressing the MT1 receptor. This inhibitory effect of melatonin on cell growth was higher on MT1 transfected cells than in vector transfected ones. In MT1-transfected cells, aromatase activity (measured by the tritiated water release assay) was inhibited by melatonin (20% at 1 nM; 40% at 10 microM concentrations). The same concentrations of melatonin did not significantly influence the aromatase activity of vector-transfected cells. MT1 melatonin receptor transfection also induced a significant 55% inhibition of aromatase steady-state mRNA expression in comparison to vector-transfected MCF-7 cells (p<0.001). In addition, in MT1-transfected cells melatonin treatment inhibited aromatase mRNA expression and 1 nM melatonin induced a higher and significant down-regulation of aromatase mRNA expression (p<0.05) than in vector-transfected cells. The findings presented herein point to the importance of MT1 melatonin receptor in mediating the oncostatic action of melatonin in MCF-7 human breast cancer cells and confirm MT1 melatonin receptor as a major mediator in the melatonin signalling pathway in breast cancer. PMID- 17342342 TI - Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on lung cancer: roles of cyclooxygenase-2. AB - We examined the effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the lung cancer cell lines PC-9, LA-1 and A549. In addition, we examined if the effects of the cytokines on the cell lines are mediated by activation of cyclooxygenase (COX)-2. The three cell lines did not constitutively produce either G-CSF or GM-CSF. G-CSF did not influence cell growth in the three cell lines, while GM-CSF increased cell growth in the A549 and LA-1 lines. G-CSF and GM-CSF dose-dependently decreased cell death in the three cell lines. RT-PCR demonstrated GM-CSF receptor expression in the three lung cancer cell lines, whereas the G-CSF receptor exists only in the PC-9 line. We suggest that G-CSF might rescue the tumor cells from cytotoxicity due to serum deprivation through cellular pathways independent of the G-CSF receptor. G-CSF and GM-CSF increased cyclooxygenase-2 (COX-2) expression in PC-9 and LA-1 cells whereas they decreased COX-2 expression in A549 cells. The COX-2 inhibitor NS-398 increased cell death in PC-9 and LA-1 cells, whereas it decreased cell death in A549 cells. PC-9 and LA-1 clones transfected with sense G-CSF- or GM-CSF showed an increase in COX-2 expression, while COX-2 expression was decreased in transfected A549 clones. COX-2 expression was increased in anti-sense G-CSF- and GM-CSF-transfected A549 clones. Thus, although COX-2 activation seems to induce different biological behavior depending on the cell type, we propose that G-CSF and GM-CSF might accelerate tumor progression by directly regulating COX-2 expression, independently of an autocrine mechanism. PMID- 17342343 TI - Strong association of the tissue inhibitor of metalloproteinase-2 polymorphism with an increased risk of oral squamous cell carcinoma in Europeans. AB - The present study was performed in order to investigate the possible association of the -418 G/C polymorphism in the tissue inhibitor of metalloproteinase-2 (TIMP 2) gene, which affects its expression, with the risk of developing oral cancer. PCR-based restriction analysis was performed in DNA samples from 158 patients with oral squamous cell carcinoma (OSCC) and 168 healthy controls of equivalent sex, age and ethnicity (Greeks and Germans). Statistical analyses were performed with Fisher's exact test and the calculation of odds ratios with a 95% confidence interval (CI). The frequency of the low C allele expression was ten times greater in the patients than the controls (31% vs 2.7%, respectively; P<0.001). The C/C and G/C genotypes were associated with an increased risk of developing OSCC (P<0.001, OR=40.88, 95% CI=2.24-744.40, and P<0.001, OR=21.31, 95%=9.82-46.21, respectively). The same pattern of significant differences with the controls was also observed in the subgroups of patients in regard to the initial or advanced stages of oral cancer, family history of any type of cancer or thrombosis, and smoking habits or alcohol abuse. These findings are consistent with the reduced levels of TIMP-2 in the presence of the low expression C allele, which are insufficient to inhibit the matrix metalloproteinase-driven degradation of the extracellular matrix (leading to cancer invasion) and mitogen-driven neoangiogenesis (leading to tumor growth and metastasis). In conclusion, the studied TIMP-2 polymorphism is strongly associated with an increased risk of OSCC in Europeans carrying the low C allele expression. These results indicate that this polymorphism could serve as a genetic marker for the susceptibility of cancer in the oral cavity. PMID- 17342344 TI - Overexpression of Survivin and XIAP in MDR cancer cells unrelated to P glycoprotein. AB - Cancer cells developing multidrug resistance (MDR) is one of the most serious clinical problems responsible for the failure of cancer chemotherapy. P glycoprotein (P-gp) overexpression and inhibitor of apoptosis proteins (IAPs) overexpression in cancer cells are the two common mechanisms of MDR. However, the relationship between IAPs and P-gp in MDR cancer cells is unknown. We investigated the expression levels of two IAPs, Survivin and XIAP, and their interaction with P-gp in MDR cancer cells. We have found that the human epidermoid carcinoma cells KBv200 and breast cancer cells MCF-7/Adr overexpress not only P-gp but also XIAP and Survivin, and showed high resistance to chemotherapeutic drugs doxorubicin, docetaxel and vincristine, in contrast to their parental cells KB and MCF-7. Furthermore, upregulation of Survivin or XIAP through transfection with the plasmid pECFPN1-Survivin or pcDNA3-6myc-XIAP in these four cell sublines did not affect the P-gp expression. Downregulation of Survivin or XIAP through transfection with the Survivin or XIAP siRNA did not have an effect on the P-gp expression in these resistant cells. Additionally, our immunoprecipitation results showed that Survivin or XIAP did not directly bind to P-gp. In summary, our study suggested that the overexpression of Survivin and XIAP in MDR cancer cells does not directly interact with P-gp. PMID- 17342345 TI - Aquaporins are upregulated in glandular epithelium at the time of implantation in the rat. AB - Regulation of luminal fluid is essential for blastocyst implantation. While it has been known for quite some time that there is a reduction in the amount of luminal fluid at the time of implantation, the mechanisms regulating this process are only just emerging. Previous studies have shown an upregulation of aquaporin (AQP) 5 channels in luminal epithelial cells at the time of implantation providing a mechanism for fluid reabsorption across the surface epithelium. However to date the contribution of fluid reabsorption by glandular epithelial cells has not been established. This study using reverse transcriptase polymerase chain reaction demonstrates the presence of several AQP isoforms in the rat uterus at the time of implantation while immunofluorescence data demonstrates an apical distribution of AQPs5 and 9 in the glandular epithelium at the time of implantation. The presence of AQPs5 and 9 in the apical plasma membrane of the glandular epithelium seen in this study provides a mechanism for transcellular fluid transport across these glandular epithelial cells similar to that seen in luminal epithelial cells. The reabsorption of glandular fluid via AQP channels may also regulate luminal fluid volume and be involved in the reduction in luminal fluid seen at the time of implantation. PMID- 17342346 TI - First report of Anaplasma phagocytophilum and its co-infections with Borrelia burgdorferi sensu lato in Ixodes ricinus ticks (Acari: Ixodidae) from Republic of Moldova. AB - We examined 198 questing Ixodes ricinus ticks collected in Chisinau City, Republic of Moldova by PCR assays for Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato and co-infection of both pathogens, which were detected in 9%, 25.2% and 2.5% of tested ticks, respectively. B. burgdorferi s.l. genotyping revealed the presence of five genospecies with dominance of B. garinii. Our preliminary study provides evidence about occurrence of both pathogens in this populated area, which represent a potential health risk for inhabitants. PMID- 17342347 TI - The effect of orally administered Aloe marlothii leaves on Boophilus decoloratus tick burdens on cattle. AB - The effect of a decoction of pulverized aloe leaves (Aloe marlothii) mixed with tap water and administered orally through a gastric tube was determined against ticks on cattle. The decoction was administered to six randomly selected calves seven times at 3-day intervals while the remaining calves received an equivalent amount of tap water only. Five hours after first treatment the calves were infested with Boophilus decoloratus larvae hatched from one gram of eggs. Resultant engorged female ticks were collected, counted and weighed daily. Fertility estimates were determined for 30 engorged female ticks collected from each calf in both the treated and control groups of calves. The treatment had no significant effect on total or daily numbers of engorged females collected per group, nor on their biomasses. Fertility estimates showed the treatment group to yield a marginally higher, yet insignificant, egg laying response (ELR) and reproductive estimate (RE). PMID- 17342348 TI - Monolayers assembled from a glycolipid biosurfactant from Pseudozyma (Candida) antarctica serve as a high-affinity ligand system for immunoglobulin G and M. AB - A carbohydrate ligand system has been developed which is composed of self assembled monolayers (SAMs) of mannosylerythritol lipid-A (MEL-A) from Pseudozyma antarctica, serving for human immunoglobulin G and M (HIgG and HIgM). The estimated binding constants from surface plasmon resonance (SPR) measurement were Ka = 9.4 x 10(6) M(-1) for HIgG and 5.4 x 10(6) M(-1) for HIgM, respectively. The binding site was not in the Fc region of immunoglobulin but in the Fab region. Large amounts of HIgG and HIgM bound to MEL-A SAMs were directly observed by atomic force microscopy. PMID- 17342349 TI - [Laparoscopic resection with primary anastomosis in Hinchey stages I and II without previous abscess drainage]. AB - INTRODUCTION: Intra-abdominal abscesses in diverticulitis so far have been drained percutaneously until the acute inflammation subsides and colon resection can be carried out for restoration of continence. However this method is successful in only about half of patients and lavage lasts for 2 to 3 weeks. Therefore it has to be decided whether an early operation without prior interventional drainage can attain results similar to those of the elective operation. METHODS: We performed primary laparoscopic surgery without prior interventional drainage or colon lavage in 72 patients in Hinchey stages I and II within 12 h of hospital admission. The peri- and postoperative processes were analyzed prospectively using 115 parameters. RESULTS: There was no difference in the postoperative course of patients receiving elective surgery for recurrent diverticular disease and those undergoing surgery for acute diverticulitis (Hinchey stages I and II). The rates of surgical and general complications were identical (7.7% vs 9.6% and 9% vs 3.6%, respectively). Wound infections were noted in 7.7% and 7.2%, respectively. No case of anastomotic leakage was observed. CONSEQUENCE: Based on our prospective data (grade of evidence II), we consider laparoscopic sigmoid resection with primary anastomosis (in continuity) in Hinchey stages I and II without prior interventional drainage and colon preparation to be justified. PMID- 17342350 TI - [Appendicitis necessitatis: appendicitis perforating the abdominal wall]. AB - Perforation of the appendix through the anterior abdominal wall is a rare complication of a frequent disorder. We report on a 37-year old patient presenting with purulent secretion from the right lower abdomen. The CT scan of the abdomen revealed a perityphlitic abscess with perforation of the anterior abdominal wall. The patient underwent laparotomy with appendectomy and subsequent revision of the abdominal wall. Appendicocutaneous fistula due to perforation through the abdominal wall is a rarity. In analogy to empyema necessitatis, which would require the pleural empyema to penetrate the thoracic wall, the entity was denoted appendicitis necessitatis. PMID- 17342351 TI - [Treatment of high-normal blood pressure with angiotensin receptor blockers. TROPHY Study (Trial of Preventing Hypertension)]. PMID- 17342352 TI - Predation of wild spider monkeys at La Macarena, Colombia. AB - The killing of an adult male spider monkey (Ateles belzebuth ) by a jaguar (Panthera onca) and a predation attempt by a puma (Felis concolor) on an adult female spider monkey have been observed at the CIEM (Centro de Investigaciones Ecologicas La Macarena), La Macarena, Colombia. These incidents occurred directly in front of an observer, even though it is said that predation under direct observation on any type of primate rarely occurs. On the basis of a review of the literature, and the observations reported here, we suggest that jaguars and pumas are likely to be the only significant potential predators on adult spider monkeys, probably because of their large body size. PMID- 17342353 TI - Evolutive radiological changes of the esophagus in patients with achalasia who did not receive treatment. AB - PURPOSE: The radiological features of achalasia of the esophagus are well known and have been described. However, very little is known concerning the natural history of this disease. We aimed to determine the evolutive radiological changes of the esophagus in a group of patients with achalasia who had not previously undergone any treatment. METHODS: We undertook a prospective study of 14 patients with achalasia from a group of 205 patients. They included 9 women and 5 men who did not receive any treatment at the initial diagnosis. Two radiological parameters were evaluated: (a) the maximal internal diameter of the middle third of the thoracic esophagus in millimeters and (b) the internal diameter of the esophagogastric junction in millimeters. RESULTS: At a mean follow-up of 5-years without any treatment, there was a significant increase in the diameter of the thoracic esophagus, with a rate of "dilatation" of 6.1 mm/year. In addition, there was a significant decrease of the internal diameter of the esophagogastric junction, with a rate of "stenosis" of 1 mm/year. The lower esophageal sphincter was hypertensive in all with an incomplete relaxation. CONCLUSION: These results suggest that there is a progressive deterioration in the radiological parameters of the esophagus in patients with achalasia not treated over a 5-year period of observation. PMID- 17342354 TI - Primary closure after a carotid endarterectomy. AB - PURPOSE: The prevalences of restenosis and stroke after a carotid endarterectomy (CEA) tend to differ substantially according to the surgeon. Primary closure after a CEA was the routine procedure in our institute. The primary objectives of this study were to compare the results of patients of a primary arteriotomy closure in CEA between our own and others' results based on the findings in the literature. METHODS: One hundred and sixty-six patients who underwent a primary closure were analyzed. Perioperative neurologic deficits were determined by the neurologist. Restenosis was defined as >50% stenosis on duplex scan. The range of follow-up was 7-112 months. RESULTS: Stroke including transient ischemic attack occurred within 30 postoperative days in 3 patients and after 30 postoperative days in 1 of the 166 patients. Five patients showed >50% asymptomatic restenosis. Two patients were treated with stent insertion and one underwent reoperation. One patient showed total occlusion during the follow-up period without any neurological deficits. One patient showed 50%-70% stenosis, and no intervention was done. CONCLUSIONS: The rates of recurrent stenosis and postoperative stroke were found to be sufficiently low following a primary closure to justify the continued use of this technique. PMID- 17342355 TI - Characteristics of thymoma successfully resected by videothoracoscopic surgery. AB - PURPOSE: The inclusion criteria were established for a videothoracoscopic resection of early-stage thymoma. We retrospectively evaluated the validity of these criteria in the treatment of early-stage thymoma. METHODS: The computed tomography (CT) image characteristics and clinical information comprised these criteria. The image considerations included the location of the tumor in the anterior mediastinum, a distinct fat plane between the tumor and vital organs, unilateral tumor predominance, tumor encapsulation, the existence of residual normal-appearing thymic tissue, and no mass compression effect. All enrollees were expected to be free of pleural effusion, pericardial effusion, paralysis of the hemidiaphragm, and the encasement of great vessels. An elevation of either the serum alpha-fetoprotein or beta-human chorionic gonadotropin levels, severe chest pain, superior vena cava syndrome, hoarseness, and age less than 20 years excluded the patient from enrollment. The heterogeneous content of the tumor was not an exclusion criterion, and the tumor size was not considered important. According to the above criteria, 44 patients were enrolled between November 1999 and November 2005. RESULTS: Twenty-seven patients had stage I thymoma and 17 had stage II thymoma. All patients successfully underwent a complete tumor resection using a three-port endoscopic technique. There was no open conversion. CONCLUSIONS: Based on these criteria, we can select suitable patients to confidently perform a thoracoscopic resection of early-stage thymoma. PMID- 17342356 TI - Corpus sterni reinforcement improves the stability of primary sternal closure in high-risk patients. AB - PURPOSE: To compare standard sternal closure techniques with reinforcement longitudinal wire placement in the corpus sterni in high-risk patients undergoing open-heart surgery via median sternotomy. METHODS: The subjects of this study were 71 high-risk patients, 32 (45%) of whom underwent sternal closure by conventional methods (group 1) and 39 (55%) of whom underwent sternal closure with corpus sterni reinforcement. The patients were followed up for a mean period of 90 days. RESULTS: In group 2, none of the patients had sternal dehiscence and no revision was required, but in group 1, five (15.5%) patients had sternal dehiscence. This difference was significant between the groups (P = 0.024), but there were no significant differences in mediastinitis and mortality (P > 0.05). CONCLUSIONS: Our findings suggest that primary sternal closure with longitudinal wire reinforcement on both sides of the corpus sterni will decrease the risk of infection and improve wound-healing in parallel with a decrease in sternal dehiscence. PMID- 17342357 TI - Selection of pulmonary resection procedures to avoid postoperative complications. AB - PURPOSE: We previously found a potential predictive value in a retrospective analysis of spirometry and an expired gas analysis during the exercise. We sought to reduce postoperative cardiopulmonary complications by selecting lung tumor resection procedures based on a combination of specific preoperative cardiopulmonary function test results. METHODS: Out of the 53 patients requiring a lung tumor resection, five preoperative parameters (forced expiratory volume in 1 s for intact-side, maximal oxygen uptake, ejection fraction, occluded pulmonary artery pressure, and occluded total pulmonary vascular resistant index) were used to assign patients to one of five risk categories in order to select the optimal pulmonary resection procedure. The patients were later grouped according to their postoperative course to test the value of this procedure selection method. RESULTS: No patient died or developed severe complications after surgery. Five patients had mild complications, while 46 had a good postoperative course; the 13 deaths, in the cancer cases, included 11 from primary or metastatic cancer and 2 from other causes. The overall five-year survival was 61.4%. CONCLUSION: This method for determining a pulmonary resection procedure avoided postoperative deaths and severe cardiopulmonary complications, while achieving a good outcome. PMID- 17342358 TI - Candida in acute pancreatitis. AB - PURPOSE: A Candida infection of the pancreas, which previously was considered extremely unusual, has been increasingly reported in recent years. The present study was conducted with the aim of performing a cohort analysis of our patients with acute pancreatitis to find out the incidence, sites, and species of Candida involvement; and to evaluate the risk factors, severity, and course of illness of such patients. METHODS: A total of 335 patients with acute pancreatitis were investigated for a possible Candida infection of the pancreas from January 2000 to May 2003. The clinical records of all those patients who were positive for Candida spp. isolation from pancreatic tissue were analyzed. The clinical records of 32 more cases, randomly selected from the patients who were investigated for candidal pancreatitis but were negative for Candida spp., were also analyzed in order to compare their findings with those patients with a true Candida infection of the pancreas. RESULTS: A true or possible Candida infection was observed in 41 (12.2%) of those 335 patients and Candida tropicalis was the most common isolate (43.9%). Candida spp. were isolated from pancreatic necrotic tissue in 22 (6.6%) patients (true infection). A possible Candida infection (positive drain fluid effluents at least twice, without any Candida isolation from pre/per operative samples from pancreas) was seen in 19 (5.7%) patients. Candida was also isolated exclusively from the blood in another 19 patients with a clinical diagnosis of acute pancreatitis. A risk factor analysis showed that patients with severe injury to the pancreas, on prophylactic fluconazole, and after surgical intervention were significantly more prone to develop a Candida infection. Patients with a Candida superinfection also had a significantly increased hospital stay and higher mortality. CONCLUSION: This study thus emphasizes the important role of Candida infection in patients with acute pancreatitis and demonstrates the need for early attention. PMID- 17342359 TI - Surgical outcomes of Lichtenstein tension-free hernioplasty for acutely incarcerated inguinal hernia. AB - PURPOSE: The purpose of our study was to evaluate the short-term and long-term outcomes of emergency Lichtenstein tension-free hernioplasty for acutely incarcerated inguinal hernia. METHODS: We conducted a retrospective study of patients who underwent emergency Lichtenstein hernioplasty for acutely incarcerated inguinal hernia between September 2002 and January 2006 in a major city hospital in Thailand. We analyzed the early postoperative complications and surgical outcomes. RESULTS: All 24 patients were men, with a mean age of 53.8 +/- 19.2 years (range 19-77). There was no perioperative mortality and only two postoperative complications (8.3%): a subcutaneous fluid collection, which resolved spontaneously within 2 weeks; and a superficial surgical site infection, which was treated successfully by intravenous antibiotics. The hospital stay was 3.8 +/- 2.1 days (range 2-12). All patients attended regular follow-up visits (mean 20.2 +/- 10.7 months, range 3-43). Clinical recurrence was found in one patient (4.2%), 7 months postoperatively. CONCLUSION: Lichtenstein hernioplasty can be used effectively as an emergency operation for incarcerated inguinal hernia with a good outcome and an acceptably low rate of postoperative complications. PMID- 17342360 TI - Effects of hypertension on abdominal wall healing: experimental study in rats. AB - PURPOSE: The aim of this study was to investigate the effects of untreated and treated hypertension on abdominal wall healing. METHODS: Thirty-two spontaneously hypertensive rats (SHR) were randomly allocated into two groups: H (n = 16), untreated and E (n = 16), treated with enalapril (40 mg/kg per day). Group C (n = 16) was a nonhypertensive control group. The animals of each group were submitted to a midline laparotomy and randomly divided, according to the day on which they were killed (7th or 14th postoperative day), into subgroups of 8 animals, as follows: H-7, H-14, E-7, E-14, C-7 and C-14. On the day of their deaths, two strips of the anterior abdominal wall were collected. One strip was submitted to breaking strength measurement and the other to hydroxyproline determination. RESULTS: No mortalities or complications were observed in the six subgroups. The breaking strength in E-7 subgroup was significantly lower than in C-7 (P < 0.05). The tissue hydroxyproline levels were similar in all six subgroups (P > 0.05). CONCLUSIONS: Untreated hypertension had no effect on the abdominal wall healing of rats. Hypertensive animals treated with enalapril showed a significant decrease in abdominal wound-breaking strength on the 7th postoperative day. PMID- 17342361 TI - TIMP-3 and Phosphatidylinositol 3-kinase genes were found to be related to the progression of colon cancer in a comparison of pneumoperitoneum and laparotomy in a murine model. AB - PURPOSE: Laparoscopic surgery has been performed on a wide variety of patients because the clinical benefits of a perioperative recovery result in a better short-time outcome than an open colectomy. However, no basic and molecular biological examinations have yet to elucidate the mechanisms of such an improved outcome. METHOD: To examine the gene expression profiles of mice inoculated with colon cancer cells, the tumors, the livers and the lungs of mice were analyzed using a microarray. RESULTS: In the laparotomy and control group, we observed a significant enhancement of tumor growth in comparison to the laparoscopic group. When analyzing the genes that became more remarkably upregulated or downregulated in the laparoscopic group in comparison to those in the laparotomy or control group, we focused our attention on the TIMP-3 gene and PI3-kinase gene expression. The downregulation of TIMP-3 and the upregulation of PI3-kinase were observed. To confirm the downstream signal of the PI3-kinase gene, we examined the expression of Skp-2 gene and p27 protein. We observed the expression level of the Skp-2 to be upregulated, while the expression level of p27 protein decreased. CONCLUSIONS: The surgical procedures of a laparotomy induced a downregulation of TIMP-3 and an upregulation of PI3-kinase, which together resulted in an enhancement of cancer cell growth thus leading to an increased invasion activity and cell cycle in comparison to treatment using a laparoscopic approach. PMID- 17342362 TI - Thyroid adenoma with extensive extracellular mucin deposition: report of a case. AB - A thyroid tumor with extensive extracellular mucin deposition is extremely rare. We herein describe a case of a thyroid adenoma with prominent myxoid stroma. A 63 year-old man presented with a mass in his right anterior neck. Radiological examinations showed this mass to be a thyroid tumor with a cystic component. The histopathological findings showed the stroma of this tumor to consist of abundant myxoid materials which stained gray-bluish for hematoxylin-eosin. The myxoid material was positive for alcian blue, whereas periodic acid-Schiff did not stain this material. No intracytoplasmic mucin was identified. In an immunohistochemical study, the tumor cells were negative for cytokeratin 19. Furthermore, positive staining was observed for thyroglobulin while a negative finding was seen for calcitonin. PMID- 17342363 TI - Metastatic breast tumor arising from synovial sarcoma: report of a case. AB - We report a case of metastatic breast tumor arising from a synovial sarcoma of the lower limb. A 27-year-old Japanese woman was diagnosed to have synovial sarcoma 14 months prior to finding a mass in her left breast. An excisional biopsy was performed and a metastatic synovial sarcoma to the breast was confirmed. Eight months after the resection of the breast lesion, the patient developed local recurrences in both her knee and breast. A tumor resection of the limb lesion and a simple mastectomy for the huge lesion, which was diagnosed to be a metastatic breast tumor without lymph node metastasis, were performed. After the operation, the patient received adjuvant systemic chemotherapy. To the best of our knowledge, this is only the second reported case of a solitary metastatic breast tumor arising from synovial sarcoma. PMID- 17342364 TI - Aorto-right atrium fistula caused by detachment after Bentall's operation: report of a case. AB - A 70-year-old woman was admitted to our hospital for treatment of right heart failure 16 years after undergoing Bentall's operation with a Cabrol shunt procedure. Various investigations showed detachment of the coronary artery and graft. We surmised that the heart failure was caused by a massive left to right shunt between a pseudoaneurysm of the wrapping aortic wall and the right atrium. Intraoperatively, we found a small fistula between the wrapping aortic wall and the right atrium, with complete closure of Cabrol shunt. We performed regrafting of the ascending aorta and reconstruction of the coronary ostium under cardiopulmonary bypass. The patient had an uneventful postoperative course. Detachment of the coronary ostium is a common long-term complication of Bentall's operation, but a Cabrol shunt between the wrapping aortic wall and the right atrium rarely causes congestive heart failure. A fistula between a pseudoaneurysm and the right atrium is even more unusual. PMID- 17342365 TI - Successful reconstructive surgery for isolated mitral insufficiency associated with Williams syndrome: report of a case. AB - Isolated mitral insufficiency requiring surgical correction is extremely rare in Williams syndrome (WS). We report the case of a 25-year-old man with WS, who suffered congestive heart failure caused by severe mitral insufficiency and atrial fibrillation. We found extensive anterior leaflet prolapse, but no other cardiovascular disorders such as supra-aortic or pulmonary arterial stenosis. He underwent successful radical valve repair with a concomitant Cox-maze procedure. This reconstructive procedure was appropriate and effective surgical treatment for isolated mitral valve disease associated with WS. PMID- 17342366 TI - Out-of-hospital cardiopulmonary arrest due to penetrating cardiac injury treated by percutaneous cardiopulmonary support in the emergency room: report of a case. AB - Penetrating cardiac injury tends to generally be repaired without cardiopulmonary bypass in the operating room. We herein report the case of penetrating cardiac injury repaired using percutaneous cardiopulmonary support in an emergency room. A 57-year-old man attempted suicide by stabbing himself in the left anterior chest with a knife. Although the patient suffered cardiopulmonary arrest for 7 min in the ambulance, spontaneous circulation was restored following pericardiotomy through emergency left thoracotomy in the emergency room. To prevent coronary artery injury and control the massive bleeding, percutaneous cardiopulmonary support was instituted without systemic heparinization and the cardiac injury was repaired in the emergency room. The patient was then transferred to another hospital on day 46 for further rehabilitation. Percutaneous cardiopulmonary support might be helpful for treating critical patients in an emergency room, even in the case of trauma patients. PMID- 17342367 TI - Solitary nodal recurrence in the dorsal area of the thoracic aorta after a curative resection of esophageal cancer: report of two cases. AB - Although locoregional recurrence is often observed in the cervicothoracic area even after an esophagectomy with three-field lymph node dissection (3FL), recurrence in the mediastinal lymph nodes is relatively rare. We experienced two cases of solitary recurrence in a posterior mediastinal node (No 112-ao) after a curative resection for thoracic esophageal cancer. The lymph node recurrence was located in the connective tissue adjacent to the left posterior wall of the thoracic aorta, and thus could not have been removed by the conventional approach of an esophagectomy through a right thoracotomy. These two patients underwent surgical removal of the tumor through left thoracotomy, and survived for 5 years and 1 year without recurrence, respectively. Because the rate of metastasis in this area appears to be low, it is not always necessary to perform complete nodal dissection of the left side of the descending aorta at the initial surgery in cases of thoracic esophageal cancer. However, our experience suggests the importance of periodic computed tomography scans to check for any nodal recurrence in this area, since a surgical resection may be effective when the recurrence is detected as a solitary metastasis. PMID- 17342368 TI - Kidney metastasis of resected early gastric carcinoma: report of a case. AB - We report a rare case of kidney metastasis of resected early gastric cancer in a 67-year-old man. We performed distal gastrectomy with D2 lymph node dissection for early gastric cancer, which was histologically diagnosed as moderately differentiated adenocarcinoma (T1N0M0, stage IA). Preoperatively, his serum carcinoembryonic antigen (CEA) level was 9.5 ng/ml, and this dropped to 7.0 ng/ml postoperatively. However, 1 year 10 months after the operation, we performed partial kidney resection and the lesion was confirmed to be a metastasis of the gastric cancer. Unfortunately, 5 months later, multiple liver metastasis was found, accompanied by a further increase in the serum CEA level to 2 650.8 ng/ml. This case illustrates the poor prognosis associated with a high preoperative serum CEA level, even if early gastric cancer is resected curatively. PMID- 17342369 TI - Prothrombin 20210 G/A defect as a cause of mesenteric venous infarction: report of a case. AB - A 50-year-old man with abdominal pain, nausea, and vomiting presented at our emergency department. Physical examination revealed diffuse abdominal tenderness and absent bowel sounds. Computed tomography showed partial portal vein thrombosis extending to the right portal vein and the superior mesenteric vein, perfusion defects in the liver, and nonopacified intestinal segment after contrast injection. An emergency laparotomy was performed. The wall of the distal jejunum was edematous, congested, and a 10-cm jejunal segment was necrotic. A partial intestinal resection and a primary anastomosis were performed. Screening for thrombophilia revealed a heterozygote 20210 G/A mutation of the prothrombin gene. Anticoagulation was initiated. Computed tomography 45 days after surgery showed a complete dissolution of the thrombi and cavernous transformation in the main portal vein. His subsequent clinical course was uneventful. Mesenteric venous thrombosis which causes an intestinal infarction is rare, and also difficult to diagnose. However, a prothrombin 20210 defect should be considered in the differential diagnosis of patients with unexplained thrombosis. PMID- 17342370 TI - Uncontrollable intra-abdominal bleeding necessitating low anterior resection of the rectum after stapled hemorrhoidopexy: report of a case. AB - Stapled hemorrhoidopexy (SH) has become a widely accepted surgical procedure for hemorrhoids; however, one of the most serious complications of this technique is severe bleeding. We report a case of extensive hemoperitoneum after SH for third degree hemorrhoids. On postoperative day (POD) 1, the patient complained of severe abdominal pain and clinical signs of peritonitis soon became evident. Computed tomography (CT) showed blood in the abdomen. We performed an emergency exploratory laparotomy, which revealed extensive hemoperitoneum, and a devitalized, edematous rectum with a tense hematoma, approximately 1 cm above the staple line and extending up to the level of the peritoneal reflection. We also found a small seromuscular laceration in the anterior aspect of the rectum just above the peritoneal reflection. This small laceration was bleeding actively. Thus, we performed a low anterior resection and the patient was discharged from hospital 10 days later. We report this case to raise awareness of the possibility of life-threatening intra-abdominal complications without evidence of typical rectal bleeding. PMID- 17342371 TI - Abdominal cocoon in an aged man: report of a case. AB - An abdominal cocoon is an extremely rare condition, which has been mainly reported in young adolescent women as a cause of small bowel obstruction. In these patients the small bowel is encased in a fibrous sac called an abdominal cocoon. We herein describe a 74-year-old man who demonstrated an abdominal cocoon without having any history associated with an abdominal cocoon. A laparotomy showed bloody ascites and the entire small bowel was encased in a thin white fibrous membrane like a cocoon. The small intestine entered into a defect of the membrane, thus presenting as an internal hernia with intestinal necrosis. The necrotic intestine and the membrane were removed. A histopathological examination of the membrane showed a few signs of inflammation cells. PMID- 17342373 TI - HER2 expression in gastrointestinal carcinoid tumors: high in intestinal but not in gastric tumors. AB - We investigated HER2 expression immunohistochemically in 12 patients with a gastrointestinal (GI) carcinoid tumor. The tumors were located in the stomach in three patients, the duodenum in four, the vermiform appendix in one, and the rectum in four. HER2 was highly expressed in the nine intestinal, but not in the three gastric carcinoid tumors. These findings suggest that HER2 might be highly expressed in intestinal, but not in gastric, carcinoid tumors. PMID- 17342372 TI - Surgical treatment of patients with wandering spleen: report of six cases with a review of the literature. AB - Wandering spleen, which is defined as a spleen without peritoneal attachments, is a rare disease and a delay in the clinical and/or radiological diagnosis may lead to splenic torsion, infarction, and necrosis. Owing to the physiologic importance of the spleen, especially in children, and the risk of postsplenectomy sepsis, early diagnosis and splenopexy are recommended. In the present article, we describe the results of our management of this rare problem on six patients, and we review all available literature from 1895 to 2005. Briefly, our technique includes flap creation from parietal peritoneum and settlement of spleen in the fossa splenica. Free edges of this flap are stitched to the stomach and the left end of transverse colon and the beginning of the descending colon. The body of the stomach was stitched to the abdominal wall to prevent gastric volvulus, while the fundus region was fixed to the diaphragm to support the spleen. Finally, an omental patch was stitched to the intact abdominal wall above the flap. In conclusion, the procedure of splenopexy without using mesh is considered to be a safe and curative modality for wandering spleen without imposing any undue risk of infection or foreign material reaction. PMID- 17342375 TI - Pressure variation of reentrant transition temperature in liquid crystals. AB - High pressure experimental studies show that in certain mesogenic materials, the nematic-smectic A (N-Sm A) transition temperature T(AN) exhibits nonlinear pressure dependence. As a consequence, the material shows reentrant phenomena that is a phase sequence nematic -- smectic A -- reentrant nematic appears. The characteristic features of this phenomenon have been addressed here within the framework of Landau-de-Gennes theory, where the coupling between nematic and smectic A order parameters (gamma, lambda(eff)) plays an important role. The cubic coupling gamma is chosen to be negative in order to form Sm A phase whereas the biquadratic coupling lambda(eff) is made large and positive to obtain reentrant behaviour. In the present work, we incorporate the pressure dependence in the theory through gamma and lambda(eff) which justifies the experimental pressure dependence in the reentrant transition temperature [Formula: see text]. The pressure dependence of gamma and lambda(eff) are employed in the calculation of excess specific heat capacity near the reentrant transition. The computed heat capacity shows strong pressure dependence near the reentrant transition which can be confirmed from high pressure measurement. PMID- 17342376 TI - On the existence of stationary states during granular compaction. AB - When submitted to gentle mechanical taps a granular packing slowly compacts until it reaches a stationary state that depends on the tap characteristics. The properties of such stationary states are experimentally investigated. The influence of the initial state, taps properties and tapping protocol are studied. The compactivity of the packings is determinated. Our results strongly support the idea that the stationary states are genuine thermodynamic states. PMID- 17342377 TI - Electrogenic kinetics of a mammalian intestinal type IIb Na(+)/P(i) cotransporter. AB - The kinetics of a type IIb Na(+)-coupled inorganic phosphate (Pi) cotransporter (NaPi-IIb) cloned from mouse small intestine were studied using the two-electrode voltage clamp applied to Xenopus oocytes. In the steady state, mouse NaPi-IIb showed a curvilinear I-V relationship, with rate-limiting behavior only for depolarizing potentials. The Pi dose dependence was Michaelian, with an apparent affinity constant for Pi (Km(pi)) of 10 +/- 1 microM: at -60 mV. Unlike for rat NaPi-IIa, (Km(pi)) increased with membrane hyperpolarization, as reported for human NaPi-IIa, flounder NaPi-IIb and zebrafish NaPi-IIb2. The apparent affinity constant for Na(+) (Km(na)) was 23 +/- 1 mM: at -60 mV, and the Na(+) activation was cooperative with a Hill coefficient of approximately 2. Pre-steady-state currents were documented in the absence of Pi and showed a strong dependence on external Na(+). The hyperpolarizing shift of the charge distribution midpoint potential was 65 mV/log[Na]. Approximately half the moveable charge was attributable to the empty carrier. A comparison of the voltage dependence of steady-state Pi-induced current and pre-steady-state charge movement indicated that for -120 mV 0.80). Among several parameters, the T Diam was the best measure to assess the brain shift (ROC analysis) with a cut off value at 14.5 mm (91.7% sensitivity and 93% specificity). VS volume and the ratio VS volume/PF volume were also efficient to predict a brain shift. CONCLUSIONS: Max Diam and T Diam are bedside measured simple data of particular interest to respectively estimate the VS volume and predict the brain shift due to the tumour. The determination of cut-off values correlated to brain shift will provide guidelines at the time of the therapeutic decision between radiosurgical and microsurgical strategy. PMID- 17342380 TI - Detection and prevention of the trigeminocardiac reflex during skull base surgery. PMID- 17342381 TI - Report of the JRAAC on the Situation of the Accreditation Training Programmes in Europe. PMID- 17342384 TI - Small intestinal strangulation due to a primary internal paracecal hernia. AB - The discovery of a paracolic hernia is an unusual event, even for an experienced specialist in colorectal surgery. We report a case of a 59-year-old woman with no previous history of abdominal surgery, who presented to the Emergency Department complaining of episodic abdominal pain and distension accompanied by a palpable mass in the right lower quadrant. At laparotomy, a paracecal hernia with small bowel volvulation was found. The prime objective of this report is to draw the clinician's attention to the necessity of making a rapid diagnosis of internal hernias. PMID- 17342383 TI - A pilot study on the use of a plasma skin regeneration device (Portrait PSR3) in full facial rejuvenation procedures. AB - A new modality, the Portrait plasma skin regeneration (PSR(3)) system, allows precise and rapid treatment of photo-damaged skin, with controlled thermal injury and modification. Radio frequency (RF) energy converts nitrogen gas into plasma within the handpiece. Rapid heating of the skin occurs as the plasma rapidly gives up energy to the skin. This energy transfer is not chromophore dependent. The gold standard, carbon dioxide (CO(2)) laser resurfacing, has decreased in popularity due to high morbidity and downtime. There is demand for a technology that can provide the degree of improvement obtained with resurfacing without the complications associated with its use. This study evaluated the PSR(3) technology in full facial procedures. A two-site prospective study evaluated safety and efficacy for a single pass treatment of the full face using the Portrait PSR(3) system. Improvement in skin texture, tone, fine lines, dyschromia, and rhytides were assessed. Two-millimeter punch biopsy specimens were taken pre- and 90 days post-treatment. Follow-up was performed at days 2, 5, 7, 30, and 90 post treatment to monitor recovery, improvement, and any subsequent sequelae. Patients developed erythema and edema shortly after treatment, with no immediate epidermal loss or charring. Epidermal loss occurred in the subsequent 24-48 h followed by epidermal recovery in approximately 7 days. Histological investigation showed regenerative epidermal and dermal architecture. The Rhytec Portrait PSR(3) system provides an attractive alternative to standard lasers that is well tolerated by patients, stimulates collagen remodeling, and provides excellent clinical outcomes. PMID- 17342385 TI - Right-sided Bochdalek hernia obstructing in an adult: case report and review of the literature. AB - Bochdalek hernias on the right side of the diaphragm are very rarely diagnosed in adults. We review a case of a 35-year-old female who presented acutely with intestinal obstruction. Plain and cross-sectional imaging identified a large right-sided Bochdalek hernia, containing colon, causing a mechanical obstruction and, surprisingly, concurrent appendicitis. The patient underwent an emergency laparotomy. At surgery the colon was reduced and was viable. The diaphragmatic defect was repaired using non-absorbable sutures and an appendicectomy was then performed for purulent appendicitis. She made an uneventful recovery and remains well at 9-month follow-up. We discuss what we believe to be the first reported case of an obstructed right-sided Bochdalek's hernia associated with appendicitis in an adult and review the published literature on this rare condition. PMID- 17342387 TI - Characteristics and quality of randomized controlled trials in the treatment of hepatocellular carcinoma. AB - Although many randomized controlled trials (RCTs) have been performed to date in the field of the treatment for hepatocellular carcinoma (HCC), there has not been any detailed analysis or evaluation of the quality of these RCTs. This study analyzed the characteristics and quality of RCTs investigating the treatment of HCC. A MEDLINE search was performed to identify prospective RCTs investigating HCC treatment published between 1991 and 2005. Eligible RCTs were analyzed by using several items, such as publication year, geographic area, and study theme. Moreover, all RCTs were evaluated by grading five items, including sample size, calculation of sample size, intention-to-treat analysis, mean observational period, loss to follow-up rate, and summing of each point. Seventy-five articles were eligible for review. Geographically, more than half of RCTs (46 RCTs) were performed in Asia, 25 RCTs in Europe, and 3 RCTs in North America. RCTs concerning transarterial chemoembolization were most frequently performed, and RCTs on hormonal therapy, ablation therapy, and chemotherapy follow thereafter in numerical order. The mean total scores were not high, although scores have recently increased. The six high-grade RCTs were all published in the recent 5 years. Many RCTs on the treatment of HCC have been performed all over the world, especially in Asia and Europe. The quality of these RCTs is, however, unsatisfactory and most of the RCTs are still inadequately performed. High quality RCTs are needed to establish common therapeutic guidelines. PMID- 17342386 TI - Down-regulation of PGE2 by physiologic levels of celecoxib is not sufficient to induce apoptosis or inhibit cell proliferation in human colon carcinoma cell lines. AB - This study was performed to evaluate whether down-regulation of prostaglandin E(2) (PGE(2)) synthesis by celecoxib treatment is associated with inhibition of cell growth in human colon carcinoma cell lines. Physiologic concentrations of celecoxib (5-10 microM) inhibited 80% to 90% of PGE(2) production in HT-29 cells that express high levels of COX-2 protein. In these concentrations, celecoxib had a minor inhibitory effect (20-30%) on cell growth. There was a significant change in induction of apoptosis only at higher concentrations of celecoxib (>20 microM). Treatment by low concentrations of celecoxib did not alter the levels of COX-1, beta-catenin, P(27), Bcl-2, and Bcl-x proteins. The effect of celecoxib on cell growth inhibition was higher on the COX-2-positive HT-29 cell line (IC(50)=20 microM) than on the COX-2 deficient SW-480 cell line (IC(50)=35 microM). In conclusion, inhibition of PGE(2) synthesis is an early, but not sufficient, step in the mechanism of celecoxib-mediated cell growth inhibition. These results support the need for additional evaluation of independent COX-2 pathways of celecoxib in chemoprevention of CRC. PMID- 17342388 TI - CA 19-9 to rule out pancreatic or biliary cancer among patients with cholestasis: an unsuitable test? PMID- 17342389 TI - Giant heterotopic pancreas presenting with massive upper gastrointestinal bleeding. AB - Heterotopic pancreas, or pancreatic rest, refers to extra-pancreatic tissue without an obvious vascular or anatomic connection with the pancreas. Although the frequency of heterotopic pancreatic tissue in autopsy series has been reported as high as 14%, clinical manifestations are rare [2]. Although common in the upper gastrointestinal tract, heterotopic pancreatic tissue rarely causes gastrointestinal bleeding. In a large case series following patients with heterotopic pancreatic tissue, only 7 of 212 patients had any evidence of bleeding [3]. We present a patient who presented with massive hematochezia found to have a giant heterotopic pancreas in the duodenum. PMID- 17342390 TI - Cutaneous and colonic metastases after resection of hepatocellular carcinoma. PMID- 17342391 TI - Hepatic glycogenosis: an underrecognized source of abnormal liver function tests? PMID- 17342392 TI - Rebamipide contributes to reducing adverse effects of long-term administration of omeprazole in rats. AB - Proton pump inhibitors (PPIs) have become of great importance for the treatment of peptic ulcer disease and gastroesophageal reflux disease. However, these drugs have several adverse effects, including worsening of corpus atrophic gastritis in patients with H. pylori infection, various histological changes including fundic gland-type polyps, inhibition of glycoprotein production, and hypergastrinemia. On the other hand, it has been reported that rebamipide, a gastroprotective drug, has the potential to increase mucous secretion and basically regulate physiological defensive functions aimed to maintain tissue integrity. In this study, we attempted to clarify whether rebamipide improves morphological changes and hypergastrinemia after administration of omeprazole (OPZ) for 1 year in rats. Eight-week-old male Wistar rats were used. Rats were divided into four groups according to diet as follows: 100 mg/kg body weight OPZ group, 100 mg/kg body weight OPZ and 30 mg/kg body weight rebamipide (OPZ + trebanipide group), 30 mg/kg body weight rebamipide, and normal diet (CRF-1). Morphological changes in gastric mucosa in all groups were studied using hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemical staining for alpha amylase. Serum gastrin level and basal acid secretion were also examined. In the OPZ group, cystic degenerations with amorphous eosinophilic contents, decreased mucous secretion, decreased chief cells, and development of pancreatic acinar cell metaplasia were detected. However, in the OPZ+rebamipide group, these morphological changes were significantly milder than in the OPZ group. Serum gastrin level and basal acid secretion in the OPZ group increased significantly compared to those in the control group. But these factors in the OPZ+rebamipide group were almost normalized (similar to those of control animals). In conclusion, long-term OPZ treatment causes various morphological changes, hypergastrinemia, and basal acid hypersecretion. The present results suggest that rebamipide contributes to reducing these adverse effects caused by long-term OPZ treatment in rats. PMID- 17342393 TI - Metachronous small bowel adenocarcinomas detected by capsule endoscopy in a patient with hereditary nonpolyposis colorectal cancer. PMID- 17342394 TI - Corticosteroid-responsive Cronkhite-Canada syndrome complicated by thrombosis. PMID- 17342395 TI - Video capsule endoscopy to diagnose metastatic melanoma. PMID- 17342397 TI - Collagenous gastritis: endoscopic and pathologic evaluation of the nodularity of gastric mucosa. PMID- 17342396 TI - Total parenteral nutrition leads to alteration of hepatocyte cell cycle gene expression and proliferation in the mouse. AB - Total parenteral nutrition (TPN) is correlated with progressive liver injury. Such injury may be associated with either an increase or decrease in hepatocyte growth. The goal of these experiments was to determine TPN-related alterations in intrahepatic genes, as they relate with the cell cycle, using microarray techniques. After 7 days of infusion of saline or TPN-solution, hepatocyte gene expression was examined with a 5000-cDNA microarray chip. TPN was associated with an up-regulation of the cyclin kinase Cdc25B mRNA, which controls the cell cycle at the G2/M phase. Based on this, our studies were directed at alterations in genes related to mitosis in this phase of the cell cycle. mRNA expression of mitotic phase inducers and inhibitors were examined. Cdc25B1 mRNA expression increased with TPN. TPN also led to additional significant alterations in the expression of other factors which mediate proliferation in this phase of mitosis. Histologically, TPN resulted in a significant decline in hepatocyte proliferation. Coincident with the alteration in cyclin expression was a significant decrease in hepatocytes in the G2/M phase with TPN administration. This study demonstrates significant alterations in cell cycle gene expression with TPN. The findings correlate with a loss of hepatocyte proliferation and may give insight into the potential mechanism of TPN-induced hepatocyte injury. PMID- 17342398 TI - Cellular localization, binding sites, and pharmacologic effects of TFF3 in experimental colitis in mice. AB - Trefoil factors (TFFs) are essential for protection and restitution of the gastrointestinal mucosa but many aspects of TFF biology are unclear. Our aim was to compare the localization of endogenous TFFs and binding sites for injected TFF3 in the colon of healthy and colitic mice and to study the effect of TFF3 on dextrane sulfate sodium (DSS)-induced colitis in mice. Expression of endogenous TFF1-3 was examined by in situ hybridization and immunohistochemistry, and the distribution of intravenously, intraperitoneally, and subcutaneously administered (125)I-TFF3 by autoradiography and gamma-counting. The effect of systemically administered TFF3 on DSS-induced colitis was assessed. We found increased expression of endogenous TFF3 and increased binding of injected (125)I-TFF3 in the colon of animals with DSS-induced colitis. The distribution of intraperitoneally and subcutaneously administered (125)I-TFF3 was comparable. Systemic administration of the peptides reduced the severity of colitis. Expression of endogenous TFF3 and binding of systemically administered TFF3 are increased in DSS-induced colitis. Systemic administration of TFF3 attenuates the disease. These findings suggest a role of TFF3 in mucosal protection. PMID- 17342399 TI - Phlegmonous gastritis in a 32-week pregnant woman managed by conservative surgical treatment and antibiotics. AB - Phlegmonous gastritis is an extremely rare and life-threatening condition. We report the case of a 32-week pregnant women presenting a peritonitis owing to phlegmonous gastritis caused by a group A streptococcus and successfully managed by conservative surgical treatment and antibiotics. Multiple endoscopies with biopsies illustrate progressive and complete gastric recovery. PMID- 17342400 TI - A rare gastric outlet anomaly: pyloric ostium on incissura angularis. AB - Congenital gastric outlet anomalies are rarely seen defects resulting from early embryologic development of foregut. We report a case of congenital pyloric outlet anomaly in a 60-year-old man with mild postprandial epigastric discomfort of approximately 3 months' duration. Endoscopic examination of the stomach showed a pyloric ostium on incissura angularis connecting the stomach to the duodenum. Usual site of pylorus at the end of antrum was closed like a sac. No signs of acute or chronic peptic ulcer were noted. A biopsy was taken from the region showed normal mucosal layers with a mild gastritis. There was no history of surgery, ulcer disease, or use of any medication. The case was considered to be congenital in origin and was successfully treated conservatively with proton-pump inhibitors and gastrokinetics. PMID- 17342401 TI - Morbid obesity causes chronic increase of intraabdominal pressure. AB - Intraabdominal hypertension and the abdominal compartment syndrome are known to deleteriously affect a wide array of organ systems. We retrospectively reviewed 62 women who underwent either laparoscopic gastric bypass surgery or adjustable gastric banding. Their age, body mass index (BMI), and race were known. Their opening abdominal pressure was recorded by connecting a Verress needle to a pressure monitor. Linear regression was used to assess the contribution of age, race, and BMI to the observed variation in opening abdominal pressure. Neither variation in age or race explained the variation in opening pressure (P > .05). By contrast, variation in BMI explained 8% of the observed variation in opening pressure (P < .05). For every 1 kg/mm(2) increase in BMI, there was on average a 0.07 mm Hg increase in opening pressure. Increases in BMI are associated with increases in intraabdominal pressure. PMID- 17342402 TI - Proton pump inhibitors: effective first-line treatment for management of dyspepsia. AB - The aim of this study was to evaluate the reasons for trial exclusion among dyspeptic patients and estimate the proportion that may have benefited from proton pump inhibitor (PPI) therapy. Stringent inclusion criteria for enrollment in two multicenter functional dyspepsia trials included dyspepsia (predominant persistent/recurrent upper abdominal discomfort [UAD] during the prior 3 months) of at least moderate intensity during > or =30% of days during the prior 2 to 3 weeks. Exclusion criteria were mild/infrequent UAD; heartburn and UAD of equal frequency; predominant heartburn with UAD; endoscopic evidence of erosive esophagitis or Barrett's or gastric and/or duodenal erosions (>5) or ulcers; irritable bowel syndrome (IBS); other gastrointestinal diagnoses; or other "non categorized" disorders. Of 2,588 screened patients, 1,667 were excluded. Excluded patients by category had mild/infrequent UAD (12.5%, n=324), heartburn and UAD of equal frequency (1.1%, n=29), predominant heartburn with UAD (11.6%, n=300), endoscopic evidence of erosive esophagitis or Barrett's (6.2%, n=160), gastric and/or duodenal erosions (1.4%, n=36), gastric and/or duodenal ulcers (2.0%, n=53), IBS (7%, n=180), "other" gastrointestinal diagnoses (2.8%, n=73), or other "non-categorized" disorders (19.8%, n=512). Fifty-four percent of patients (902/1,667) had symptoms/diagnoses that would be expected to improve with PPI therapy. Individuals with IBS, "other," or "non-categorized" disorders were considered to have symptoms unlikely to respond to PPI treatment. Empiric PPI treatment would be expected to provide symptom relief to the majority of dyspepsia sufferer who present in clinical practice. PPIs represent the best currently available therapy for acid-related disorders and should be considered the first-line management approach in patients with uninvestigated dyspepsia. PMID- 17342403 TI - Reduced severity of a mouse colitis model with angiotensin converting enzyme inhibition. AB - Ulcerative colitis is characterized by elevated rates of epithelial cell apoptosis, and an up-regulation of pro-apoptotic cytokines including tumor necrosis factor alpha (TNF-alpha). Recently, angiotensin converting enzyme (ACE) has been shown to promote apoptosis. In addition, pharmacologic ACE inhibition (ACE-I) both prevents apoptosis and reduces TNF-alpha expression in vitro. We hypothesized that ACE-I, using enalaprilat, would decrease colonic epithelial cell apoptosis and reduce colitis severity in the dextran sulfate sodium (DSS) induced colitis model in mice. We assessed the severity of colitis, and colonic epithelial cell apoptosis, after administration of DSS. Mice were given either daily ACE-I treatment or daily placebo. ACE-I treatment markedly improved clinical outcomes. In addition, ACE-I treatment significantly reduced the maximum histopathologic colitis grade. ACE-I also dramatically reduced the epithelial apoptotic rate. To investigate the mechanism by which ACE-I reduced apoptosis; we measured TNF-alpha, Bcl-2, and Bax expression. TNF-alpha mRNA was significantly lower with ACE-I treatment compared to placebo at every time point, as was the ratio of Bax to Bcl-2. We conclude that ACE-I reduces the severity of DSS-induced colitis and reduces epithelial cell apoptosis. PMID- 17342404 TI - Successful treatment with corticosteroid and lamivudine for autoimmune hepatitis in a patient with asymptomatic HBV infection. PMID- 17342405 TI - Analysis of the 3' variable region of the cagA gene of Helicobacter pylori isolated in Koreans. AB - CagA protein of Helicobacter pylori is injected into epithelial cells, and it undergoes tyrosine phosphorylation, resulting in inducing cytoskeletal rearrangements. A few studies have suggested that the number of CagA tyrosine phosphorylation motifs (EPIYA) and subtypes of CagA were associated with gastric cancer. This study was performed to characterize the 3' variable regions of the cagA gene of H. pylori and to investigate whether or not there is any relationship between the diversities of cagA and the disease outcome in Korea. Seventy-nine patients (chronic gastritis, 15; duodenal ulcer, 27; benign gastric ulcer, 18; gastric cancer, 19) were enrolled. Biopsy specimens were taken from the antrum for H. pylori culture, and genomic DNA was extracted. PCR and DNA sequence analysis was carried out for the 3' variable region of the cagA gene. Seventy-eight strains (98.8%) contained three EPIYA motifs and one strain (1.2%) isolated from a patient with duodenal ulcer contained four EPIYA motifs. Seventy six strains (96.2%) were the East Asian type. In conclusion, there was no significant difference between the number of EPIYA motifs or CagA subtypes and various gastroduodenal diseases in Korea. PMID- 17342406 TI - Foreword. PMID- 17342407 TI - Gene expression alterations in the sphingolipid metabolism pathways during progression of dementia and Alzheimer's disease: a shift toward ceramide accumulation at the earliest recognizable stages of Alzheimer's disease? AB - There is mounting evidence linking Abeta42 generation in Alzheimer's disease (AD) with sphingomyelin catabolism. Using microarray technology to study 17 brain regions from subjects with varying severity of AD and dementia we detected multiple gene expression abnormalities of the key enzymes that control sphingolipid metabolism. These changes were correlated with the progression of clinical dementia. The upregulation of gene expression of the enzymes controlling synthesis de novo of Cer and the downregulation of the enzymes involved in glycosphingolipid synthesis was evident as early in disease progression as in mild dementia. Together these changes suggest a shift in sphingolipid metabolism towards accumulation of Cer, depletion of glycosphingolipids and the reduction of synthesis of the anti-apoptosis signaling lipid-sphingosine 1-phosphate as a function of disease progression. This disrupted balance within the sphingolipid metabolism may trigger signaling events promoting neurodegeneration across cortical regions. This potential mechanism may provide a link between lipid metabolism disturbance and AD. PMID- 17342408 TI - Indices of metabolic dysfunction and oxidative stress. AB - Metabolic alterations are a key player involved in the onset of Alzheimer disease pathophysiology and, in this review, we focus on diet, metabolic rate, and neuronal size differences that have all been shown to play etiological and pathological roles in Alzheimer disease. Specifically, one of the earliest manifestations of brain metabolic depression in these patients is a sustained high caloric intake meaning that general diet is an important factor to take in account. Moreover, atrophy in the vasculature and a reduced glucose transporter activity for the vessels is also a common feature in Alzheimer disease. Finally, the overall size of neurons is larger in cases of Alzheimer disease than that of age-matched controls and, in individuals with Alzheimer disease, neuronal size inversely correlates with disease duration and positively associates with oxidative stress. Overall, clarifying cellular and molecular manifestations involved in metabolic alterations may contribute to a better understanding of early Alzheimer disease pathophysiology. PMID- 17342409 TI - Brain MR imaging and proton MR spectroscopy in female mice with pyruvate dehydrogenase complex deficiency. AB - Pyruvate dehydrogenase complex (PDC) deficiency is an inborn metabolic disorder that causes neurological abnormalities. In this report, a murine model of PDC deficiency was analyzed using histology, magnetic resonance (MR) imaging and MR spectroscopy (MRS) and the results compared to PDC-deficient female patients. Histological analysis of brains from PDC-deficient mice revealed defects in neuronal cytoarchitecture in grey matter and reduced size of white matter structures. MR results were comparable to previously published clinical MR findings obtained from PDC-deficient female patients. Specifically, a 15.4% increase in relative lactate concentration, 64.4% loss of N-acetylaspartate concentration and a near complete loss of discernable glutamine plus glutamate concentration were observed in a PDC deficient mouse compared to wild-type control. Lower apparent diffusion coefficients (ADCs) were observed within the brain consistent with atrophy. These results demonstrate the usefulness of this murine model to systematically evaluate the beneficial effects of dietary and pharmacological interventions. PMID- 17342410 TI - Branched chain keto-acids exert biphasic effects on alpha-ketoglutarate stimulated respiration in intact rat liver mitochondria. AB - Pathophysiological concentrations of branched chain keto-acids (BCKAs), such as those that occur in maple syrup urine disease, inhibit oxygen consumption in liver homogenates and brain slices and the enzymatic activity of alpha ketoglutarate- and pyruvate dehydrogenase complexes. Consistent with previous work, studies in isolated rat liver mitochondria indicate that three BCKAs, alpha ketoisocaproate (KIC), alpha-keto-beta-methylvalerate (KMV) and alpha ketoisovalerate (KIV), preferentially inhibited State 3 respiration supported by alpha-ketoglutarate relative to succinate or glutamate/malate (KIC, >100-fold; KMV, >10-fold; KIV, >4-fold). KIC was also the most potent inhibitor (K(i,app) 13 +/- 2 muM). Surprisingly, sub-inhibitory concentrations of KIC and KMV can markedly stimulate State 3 respiration of mitochondria utilizing alpha ketoglutarate and glutamate/malate, but not succinate. The data suggest that physiological concentrations of the BCKAs may modulate mitochondrial respiration. PMID- 17342411 TI - Hypoxia inducible factor prolyl 4-hydroxylase enzymes: center stage in the battle against hypoxia, metabolic compromise and oxidative stress. AB - Studies of adaptive mechanisms to hypoxia led to the discovery of the transcription factor called hypoxia inducible factor (HIF). HIF is a ubiquitously expressed, heterodimeric transcription factor that regulates a cassette of genes that can provide compensation for hypoxia, metabolic compromise, and oxidative stress including erythropoietin, vascular endothelial growth factor, or glycolytic enzymes. Diseases associated with oxygen deprivation and consequent metabolic compromise such as stroke or Alzheimer's disease may result from inadequate engagement of adaptive signaling pathways that culminate in HIF activation. The discovery that HIF stability and activation are governed by a family of dioxygenases called HIF prolyl 4 hydroxylases (PHDs) identified a new target to augment the transcriptional activity of HIF and thus the adaptive machinery that governs neuroprotection. PHDs lose activity when cells are deprived of oxygen, iron or 2-oxoglutarate. Inhibition of PHD activity triggers the cellular homeostatic response to oxygen and glucose deprivation by stabilizing HIF and other proteins. Herein, we discuss the possible role of PHDs in regulation of both HIF-dependent and -independent cell survival pathways in the nervous system with particular attention to the co-substrate requirements for these enzymes. The emergence of neuroprotective therapies that modulate genes capable of combating metabolic compromise is an affirmation of elegant studies done by John Blass and colleagues over the past five decades implicating altered metabolism in neurodegeneration. PMID- 17342412 TI - Intersection between mitochondrial permeability pores and mitochondrial fusion/fission. AB - The goal of this review is to highlight recent developments in the field of mitochondrial membrane processes, which provide new insights into the relation between mitochondrial fission/fusion events and the mitochondrial permeability transition (MPT). First, we distinguish between pore opening events at the inner and outer mitochondrial membranes. Inner membrane pore opening, or iMPT, leads to membrane depolarization, release of low molecular weight compounds, cristae reorganization and matrix swelling. Outer membrane pore opening, or oMPT, allows partial release of apoptotic proteins, while complete release requires additional remodeling of inner membrane cristae. Second, we summarize recent data that supports a similar temporal and physical separation between inner and outer mitochondrial membrane fusion events. Finally, we focus on cristae remodeling, which may be the intersection between oMPT and iMPT events. Interestingly, components of fusion machinery, such as mitofusin 2 and OPA1, appear to play a role in cristae remodeling as well. PMID- 17342413 TI - Genetic influences on outcome following traumatic brain injury. AB - Several genes have been implicated as influencing the outcome following traumatic brain injury (TBI). Currently the most extensively studied gene has been APOE. APOE can influence overall and rehabilitation outcome, coma recovery, risk of posttraumatic seizures, as well as cognitive and behavioral functions following TBI. Pathologically, APOE is associated with increased amyloid deposition, amyloid angiopathy, larger intracranial hematomas and more severe contusional injury. The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition, disruption of cytoskeletal stability, cholinergic dysfunction, oxidative stress, neuroprotection and central nervous system plasticity in response to injury. Other putative genes have been less extensively studied and require replication of the clinical findings. The COMT and DRD2 genes may influence dopamine dependent cognitive processes such as executive/frontal lobe functions. Inflammation which is a prominent component in the pathophysiological cascade initiated by TBI, is in part is mediated by the interleukin genes, while apoptosis that occurs as a consequence of TBI may be modulated by polymorphisms of the p53 gene. The ACE gene may affect TBI outcome via mechanisms of cerebral blood flow and/or autoregulation and the CACNA1A gene may exert an influence via the calcium channel and its effect on delayed cerebral edema. Although several potential genes that may influence outcome following TBI have been identified, future investigations are needed to validate these genetic studies and identify new genes that might influence outcome following TBI. PMID- 17342414 TI - The impact of nutrition on cognition in the elderly. AB - The possibility that nutritional manipulation may protect against cognitive decline and dementia is an inviting prospect. However data supporting a beneficial effect of a particular dietary pattern is limited. Although studies have demonstrated a health benefit to dietary plans that are high in fiber, whole grains, natural sugar and fish while maintaining lower intake in meat dairy and poultry, the ability to identify the most salient factors of these diets have been unsuccessful. Several aspects of diet have been studied in detail and provided support for potential mechanisms for improving cognition. Clinical trials have explored these mechanisms through supplementation studies with minimal benefits being observed. Continuing work to hone the mechanisms and refine our knowledge of dietary benefits is described. PMID- 17342415 TI - Enzyme-catalyzed side reactions with molecular oxygen may contribute to cell signaling and neurodegenerative diseases. AB - A link between neurodegeneration and well-characterized enzymatic and non enzymatic reactions that produce reactive oxygen species (ROS) from O(2) is well established. Several enzymes that contain pyridoxal 5'-phosphate (PLP) or thiamine diphosphate (ThDP) catalyze side reactions (paracatalytic reactions) in the presence of ambient O(2). These side reactions produce oxidants such as hydrogen peroxide [H(2)O(2)] or extremely reactive peracids [RC(O)OOH]. We hypothesize that although these enzymes normally produce oxidants at low or undetectable levels, changes in substrate levels or disease-induced structural alterations may enhance interactions with O(2), thereby generating higher levels of reactive oxidants. These oxidants may damage the enzymes producing them, alter nearby macromolecules and/or destroy important metabolites/coenzymes. We propose that paracatalytic reactions with O(2) catalyzed by PLP-dependent decarboxylases and by ThDP-dependent enzymes within the alpha-keto acid dehydrogenase complexes may contribute to normal cellular signaling and to cellular damage in neurodegenerative diseases. PMID- 17342416 TI - Testing for linkage and association across the dihydrolipoyl dehydrogenase gene region with Alzheimer's disease in three sample populations. AB - Prior case-control studies from our laboratory of a population enriched with individuals of Ashkenazi Jewish descent suggested that association exists between Alzheimer's disease (AD) and the chromosomal region near the DLD gene, which encodes the mitochondrial dihydrolipoamide dehydrogenase enzyme. In support of this finding, we found that linkage analysis restricted to autopsy-proven patients in the National Institute of Mental Health-National Cell Repository for Alzheimer's Disease (NIMH-NCRAD) Genetics Initiative pedigree data resulted in point-wise significant evidence for linkage (minimum p-value = 0.024) for a marker position close to the DLD locus. We now report case-control replication studies in two independent Caucasian series from the US and Italy, as well as a linkage analysis from the NIMH-NCRAD Genetics Initiative Database. Pair-wise analysis of the SNPs in the case-control series indicated there was strong linkage disequilibrium across the DLD locus in these populations, as previously reported. These findings suggest that testing for association of complex diseases with DLD locus should have considerable statistical power. Analysis of multi locus genotypes or haplotypes based upon three SNP loci combined with results from our previous report provided trends toward significant evidence of association of DLD with AD, although neither of the present studies' association showed significance at the 0.05 level. Combining linkage and association findings for all AD patients (males and females) results in a p-value that is more significant than any of the individual findings' p-values. Finally, minimum sample size calculations using parameters from the DLD locus suggest that sample sizes on the order of 1,000 total cases and controls are needed to detect association for a wide range of genetic model parameters. PMID- 17342417 TI - The effect of aggressive versus conventional lipid-lowering therapy on markers of inflammatory and oxidative stress. AB - PURPOSE: Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention. It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins. We aimed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress. MATERIALS AND METHODS: This was a multi-centre, double-blind, placebo-controlled trial. Patients with previous cardiovascular disease, who did not achieve low density lipoprotein (LDL) cholesterol levels <2.6 mmol/l on conventional statin therapy (simvastatin 40 mg) were randomized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks (aggressive treatment). Lipids, C-reactive protein, soluble cellular adhesion molecules, neopterin, von Willebrand Factor, and antibodies against oxidized LDL were measured at baseline and after 16 weeks. RESULTS: Lipid levels decreased significantly in the aggressive treatment group (LDL-C reduction 20.8%; P < 0.001), whereas a slight increase was observed in the conventional group (LDL-C increase 3.7%; P = 0.037). A significant reduction in antibodies against oxidized LDL was seen in the aggressive (13.4%; P < 0.001) and the conventional (26.8%; P < 0.001) group, but there was no difference between groups (P = 0.25). Furthermore, no significant differences in change in other biomarkers was observed between both groups. CONCLUSIONS: This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy. PMID- 17342418 TI - LPS suppresses expression of asialoglycoprotein-binding protein through TLR4 in thioglycolate-elicited peritoneal macrophages. AB - Macrophages are known to express various types of endocytosis receptors that mediate the removal of foreign pathogens. Macrophage asialoglycoprotein-binding protein (M-ASGP-BP) is a Gal/GalNAc-specific lectin, which functions as an endocytosis receptor. We found here that LPS is able to down-regulate the mRNA expression of M-ASGP-BP in a time-dependent manner using thioglycolate-elicited rat and mouse peritoneal macrophages. However, LPS does not modulate the mRNA expression of M-ASGP-BP from macrophages of C3H/HeN mice, which have a point mutation of TLR4, the primary LPS receptor. Furthermore, an inhibitor of NF kappaB was observed to efficiently block the suppressive effect of LPS on M-ASGP BP as well as to inhibit the phosphorylated IkappaB. These results demonstrate that the mRNA expression of M-ASGP-BP is down-regulated by the LPS-mediated TLR4 pathway involving NF-kappaB activation, suggesting that engagement of M-ASGP-BP by LPS may yield a negative signal that interferes with the LPS-induced positive signals mediated by proinflammatory cytokines. PMID- 17342419 TI - Genetic differentiation of the giant honey bee (Apis dorsata) in Thailand analyzed by mitochondrial genes and microsatellites. AB - Genetic diversity and population differentiation of the giant honey bee (Apis dorsata) in Thailand were examined. Six PCR-RFLP mitotypes were generated from digestion of the COI-COII, Cytb-tRNA(ser), ATPase6-8, and lrRNA genes with Dra I and Hin fI. Low genetic diversity (h=0.074, pi=0.032%) and a lack of genetic population differentiation between A. dorsata originating from geographically different regions were observed from mtDNA polymorphisms (P > 0.05). In contrast, microsatellite (A14, A24, and A88) polymorphisms revealed a relatively high level of genetic diversity in A. dorsata (H (o)=0.68-0.74, average number of alleles per locus=6.0-9.0). Both A24 and A88 indicated significant population differentiation between bees from the north-to-central region (north, northeast, and central regions), peninsular Thailand, and Samui Island. PMID- 17342420 TI - Prevalence of psychiatric disorders among children of different ethnic origin. AB - The present study assesses the population prevalence of DSM-IV disorders among native and immigrant children living in low socio-economic status (SES) inner city neighborhoods in the Netherlands. In the first phase of a two-phase epidemiological design, teachers screened an ethnically diverse sample of 2041 children aged 6-10 years using the Strengths and Difficulties Questionnaire (SDQ). In the second phase, a subsample of 253 children was psychiatrically examined, while their parents were interviewed. In addition, teachers completed a short questionnaire about 10 DSM-IV items. Prevalence was estimated using the best-estimate diagnosis based on parent, child and teacher information. Projected to the total population, 11% of the children had one or more impairing psychiatric disorders, which did not differ between native and non-native children. In the total group a clear relationship was observed between the prevalence of psychiatric disorders and gender, parental psychopathology, peer problems and school problems, but not among all ethnic groups separately. This study suggests that the prevalence of psychiatric disorders among non-treated minority and native children in low SES inner-city neighborhoods does not materially differ. However, associated mechanisms may be influenced by ethnicity. PMID- 17342421 TI - Comparison of risk factors for small-for-gestational-age and preterm in a Portuguese cohort of newborns. AB - OBJECTIVE: To identify risk factors for small-for-gestational-age and preterm in a Portuguese cohort of newborns. STUDY DESIGN: Socio-demographic, anthropometric, behavioural and obstetrical characteristics were evaluated in 4.193 women consecutively delivered. Term small-for-gestational-age (n = 342) and non-small for-gestational-age preterm (n = 148) were compared to non-small-for-gestational age term births (n = 3538). Adjusted odds ratios and etiologic fractions were calculated. RESULTS: Low height, low weight when entering pregnancy and low weight gain were significantly associated with small-for-gestational-age, but not preterm. These were the factors with the highest etiologic fraction for small-for gestational-age. An increased risk of small-for-gestational-age was found for women who smoked during pregnancy (OR = 2.39; 95% CI: 1.66-3.46) and began antenatal care after pregnancy first trimester (OR = 1.86; 95% CI: 1.32-2.62). Previous abortion was associated with small-for-gestational-age (OR = 1.72; 95% CI: 1.16-2.55) and previous preterm with preterm (OR = 3.20; 95% CI: 1.26-8.14). CONCLUSIONS: Low anthropometrics, smoking and late antenatal care were risk factors for small-for-gestational-age, but not preterm. Maternal anthropometrics were the factors with the highest impact on small-for-gestational-age. No factor showed a great contribution to preterm birth. PMID- 17342422 TI - Application of the method of characteristics for the study of shock waves in models of blood flow in the aorta. AB - Numerical algorithms are presented for the numerical solution of the one dimensional model of blood flow in the aorta. The pertinent hyperbolic equations are written using Riemann invariants, which are integrated along the characteristics using two efficient algorithms. Because of the hyperbolic nature of the equations shock waves are to be expected, and their occurrence is discussed. PMID- 17342423 TI - Lessons from the grey area: a closer inspection of at-risk gamblers. AB - The study takes a closer look at at-risk gamblers, with the objective to see how they differ from no-risk gamblers. The data comes from a national gambling survey in 2002, and the age group is 15-74 years. The sample consists of 4188 current gamblers with no current gambling problems or pathology. The analysis includes cross-tabulations and a logistic regression. The results show that at-risk gamblers differed substantially from no-risk gamblers in terms of demographic characteristics, gambling behaviour and the presence of other assumed risk factors. Demographic segments with a higher risk of falling into the at-risk group are men, young people, divorced or single people, and non-western immigrants. Furthermore, gambling problems in the family, beginners luck and misconceptions about winning chances significantly increased the odds for at-risk gambling. The study concludes that at-risk gamblers deserve more attention from research, that their similarity with problem gamblers increases the likelihood that many of them will eventually develop a gambling problem, and that their tendency to be superstitious about winning chances might be exploited in preventive work. PMID- 17342424 TI - The development of novel quantification assay for mitochondrial DNA heteroplasmy aimed at preimplantation genetic diagnosis of Leigh encephalopathy. AB - PURPOSE: To perform preimplantation genetic diagnosis (PGD) of Leigh encephalopathy, we developed a rapid and reliable quantification assay for the percentage of T8993G mtDNA mutation and analyzed various specimens. METHODS: We prepared the standard curve by measuring serial proportion of 8993T/G cloned plasmid DNA using real-time PCR, and measured (1) mutant DNA (known proportions by PCR-RFLP), (2) single lymphocytes from 46% mutant carrier, (3) 123 blastomeres from 20 abnormal embryos. RESULTS: (1) These were within -5 - +6% error range, (2) mean 44.3%(11-70%), (3) Five embryos harbored T8993G mutation (4-22%). Embryos from same person indicated different degrees of heteroplasmy, and blastomeres from same embryo demonstrated limited dispersion of heteroplasmy (2 11%). CONCLUSIONS: (1) This method provides rapid and reliable PGD for Leigh encephalopathy. (2) The variable heteroplasmy with somatic mitosis was suggested. (3) T8993G mutation was existed in undeveloped embryo, and the bottleneck theory was supported. The limited heteroplasmy dispersion of blastomeres from same embryo also supported reliability of PGD for T8993G mutation. PMID- 17342425 TI - Endometrial thickness and volume by three-dimensional ultrasound one week after embryo transfer to detect pregnancy. AB - PURPOSE: Determine if the evaluation of endometrium one week after embryo transfer can predict pregnancy. METHODS: Endometrial volume and thickness were evaluated by three-dimensional ultrasound in 40 patients one week after embryo transfer. These results were compared to serum pregnancy test performed one week later. RESULTS: Eighteen patients have achieved pregnancy. A significant difference was found for endometrial volume: 6.49+/-1.97 mL versus 3.40+/-1.11 mL (pregnant versus not pregnant); and thickness: 11.15+/-2.75 mm versus 9.77+/-1.85 mm. The ROC curve was used to detect the best cutoff values: endometrial volume of 3.48 mL (sensitivity-100%, specificity-68.2%) and endometrial thickness of 10.3 mm (sensitivity-72.2%, specificity-77.3%). The area under curve was significant higher for endometrial volume (0.909 versus 0.745, p=0.027). No pregnancy was achieved in women who had an endometrial volume <3.8 mL (15 patients) or thickness <7.9 mm (3 patients). CONCLUSIONS: The endometrial volume and thickness were significant higher in pregnant women and this difference was more prominent for endometrial volume. PMID- 17342426 TI - The impact of the depth of embryo replacement on IVF outcome. AB - PURPOSE: To evaluate the effect of the depth of embryo transfer replacement on clinical pregnancy rate. METHODS: Data from a total of 104 consecutive embryo transfers performed on 104 women aged 26-37 years were prospectively collected for this study. All patients underwent a standard down regulation protocol for ovarian stimulation. Oocytes retrieval were performed at 36 h after hCG administration. Embryo transfer took place at 48 h after insemination. The patients were matched in two groups according to the distance between the tip of the catheter and the uterine fundus at transfer (group A > 10 < 15 mm and group B < or = 10 mm). The same method of loading embryos into the embryo transfer catheter was used. RESULTS: Clinical pregnancy rates varied significantly (p < or = 0.05) between the two groups: 27.7% in group A and 14% in group B. The number and quality of embryos transferred did not differ between the groups. CONCLUSIONS: The results suggest that the depth of embryo replacement may be an important variable in embryo transfer technique. PMID- 17342427 TI - Structural sperm and aneuploidies studies in a case of spermatogenesis recovery after the use of androgenic anabolic steroids. AB - PURPOSE: Azoospermia may sometimes be related to the use of androgenic anabolic steroids. We report the case of an azoospermic man who had abused androgenic anabolic steroids and who recovered spermatogenesis six months after cessation of abuse and the administration of hormonal therapy. METHODS: An azoospermic 34-year old man came to Regional Referral Center for Male Infertility. The recovery of spermatogenesis was observed after the cessation of abuse of steroids and the administration of hormonal therapy. Ultrastructural analysis of sperm was carried out by transmission electron microscopy, and the meiotic segregation of chromosomes 1, 9, 18, X, Y was investigated. RESULTS: Mathematically elaborated transmission electron microscopy data highlighted seminal features close to normal fertility. Fluorescence in situ hybridisation showed a high frequency of XY disomy in sperm. CONCLUSIONS: Our findings confirm the recovery of spermatogenesis but suggest a possible relationship between altered meiotic segregation and the abuse of androgenic anabolic steroids. PMID- 17342428 TI - Enhancement of radon exposure in smoking areas. AB - Radium-226 is a significant source of radon-222 which enters buildings through soil, construction materials or water supply. When cigarette smoke is present, the radon daughters attach to smoke particles. Thus, the alpha radiation to a smoker's lungs from the natural radon daughters is increased because of smoking. To investigate whether the cigarette tobacco itself is a potential source of indoor radon, the alpha potential energy exposure level contents of radon ((222)Rn, 3.82d) and Thoron ((220)Rn, 55.60s) were measured in 10 different cigarette tobacco samples using CR-39 solid-state nuclear track detectors (SSNTDs). The results showed that the (222, 220)Rn concentrations in these samples ranged from 128 to 266 and 49 to 148 Bqm(-3), respectively. The radon concentrations emerged from all investigated samples were significantly higher than the background level. Also, the annual equivalent doses from the samples were determined. The mean values of the equivalent dose were 3.51 (0.89) and 1.44 (0.08) mSvy(-1), respectively. Measurement of the average indoor radon concentrations in 20 cafe rooms was, significantly, higher than 20 smoking-free residential houses. The result refers to the dual (chemical and radioactive) effect of smoking as a risk factor for lung cancer. PMID- 17342429 TI - Antioxidant enzyme activities of Microcystis aeruginosa in response to nonylphenols and degradation of nonylphenols by M. aeruginosa. AB - The aim of this study was to examine the effects of chemical nonylphenols (NPs) on the antioxidant system of Microcystis aeruginosa strains. The degradation and sorption of NPs by M. aeruginosa were also evaluated. High concentrations of NPs (1 and 2 mg/l) were found to cause increases in superoxidase dismutase (SOD) and glutathione-S-transferase (GST) activities and in glutathione (GSH) levels. These results suggest that toxic stress manifested by elevated SOD and GST levels and GSH contents may be responsible for the toxicity of NPs to M. aeruginosa and that the algal cells could improve their antioxidant and detoxification ability through the enhancement of enzymatic and nonenzymatic prevention substances. The observed elevations in GSH levels and GST activities were relatively higher than those in SOD activities, indicating that GSH and GST contributed more in eliminating toxic effects than SOD. Low concentrations of NPs (0.05-0.2 mg/l) enhanced cell growth and decreased GST activity in algal cells of M. aeruginosa, suggesting that NPs may have acted as a protecting factor, such as an antioxidant. The larger portion of the NPs (>60%) disappeared after 12 days of incubation, indicating the strong ability of M. aeruginosa to degrade the moderate persistent NP compounds. The sorption ratio of M. aeruginosa after a 12 day exposure to low nominal concentrations of NPs (0.02-0.5 mg/l) was relatively high (>30%). The fact that M. aeruginosa effectively resisted the toxic effects of NPs and strongly degraded these pollutants indicate that M. aeruginosa cells have a strong ability to adapt to variations in environmental conditions and that low and moderate concentrations of organic compounds may favor its survival. Further studies are needed to provide detailed information on the fate of persistent organic pollutants and the survival of algae and to determine the possible role of organic pollutants in the occurrence of water blooms in eutrophic lakes. PMID- 17342430 TI - Determination of heavy metals (Cd, Cr, Cu, Fe, Ni, Pb, Zn) by ICP-OES and their speciation in Algerian Mediterranean Sea sediments after a five-stage sequential extraction procedure. AB - Surface sediment samples (n = 18) were collected from the Algerian Mediterranean coasts and analyzed for seven metals using inductively coupled plasma-optical emission spectrometry in order to asses the distribution and bioavailability of metals and to study the anthropogenic factors affecting their concentrations. Sediment samples were size-fractionated into three sizes: 1,080-500 (coarse), 500 250 (medium), and <250 mm (fine). Bulk sediments were subjected to both sequential extraction and total digestion to evaluate the reliability of the sequential extraction procedure (SEP), while the fractions have been only sequentially extracted for metals speciation. The metals were sequentially extracted into five phases namely exchangeable (P1), carbonates (P2), Fe-Mn oxides (P3), organic (P4) and residual (P5). Metal recoveries in sequential extractions were +/-20% of the independently measured total metal concentrations; the high recovery rates indicate the good reliability of the SEP used in this study. Correlation coefficients indicated that the grain size has an effect on the distribution of metals in the investigated samples. The order of metal levels in the fractions was medium > fine > coarse for all the metals. The average total extractable metal concentrations for Cd, Cr, Cu, Fe, Ni, Pb, and Zn were 1.1, 8.8, 4.7, 1,291.3, 13.9, 5.7 and 20.4 mug/g, respectively. The northeastern shelf had the lowest metal levels while the highest were in northwestern part mainly due to the significant tourism activities in the northwestern part. Comparison of our results to Earth's crust values and to previous studies points out that our samples were relatively unpolluted with respect to the heavy metals investigated; most of the metals are not from anthropogenic sources. Enrichment factors as the criteria for examining the impact of the anthropogenic sources of heavy metals were calculated, and it was observed that the investigated samples were not contaminated with Cr, Cu, and Fe, moderately contaminated with Ni, Pb, and Cd, and contaminated with Cd in some sites. The P5 phase had the highest percents of Cr, Cu, Fe, Ni, and Zn. Cadmium and lead were predominant in the P4 phase, while Cu, Fe and Zn were distributed in the order P5 > P3 > P4 > P2 > P1. The following order of bioavailability was found with the heavy metals Pb > Cr > Cd > Ni > Zn > Cu > Fe. PMID- 17342431 TI - Monitoring, assessment and modelling using water quality data in the Saale River Basin, Germany. AB - The European Water Framework Directive (WFD) is the overall driver for this environmental study and currently requires the identification of patterns and sources of pollution (monitoring) to support objective ecological sound decision making and specific measures to enhance river water quality (modelling). The purpose of this paper is to demonstrate in a case study the interrelationship between (1) hydrologic and water quality monitoring data for river basin characterization and (2) modelling applications to assess resources management alternatives. The study deals with monitoring assessment and modelling of river water quality data of the main stem Saale River and its principal tributaries. For a period of 6 years the data, which was sampled by Environmental Agencies of the German states of Thuringia, Saxony and Saxony-Anhalt, was investigated to assess sources and indicators of pollution. In addition to the assessment a modelling exercise of the routing of different pollutants was carried out in the lower part of the test basin. The modelling is a tool to facilitate the evaluation of alternative measures to reduce contaminant loadings and improve ecological status of a water body as required by WFD. The transport of suspended solids, salts and heavy metals was modelled along a selected Saale reach under strong anthropogenic influence in terms of contaminants and river morphology between the city of Halle and the confluence with the Elbe River. The simulations were carried out with the model WASP5 which is a dynamic flood-routing and water quality model package developed by the US Environmental Protection Agency. PMID- 17342432 TI - Monitoring of coastal and transitional waters under the E.U. Water Framework Directive. AB - A set of guidelines are presented for the definition of monitoring plans in coastal and transitional (estuarine and lagoonal) systems subject to the European Union Water Framework Directive - WFD (2000/60/EC). General principles of best practice in monitoring are outlined, including (a) the definition of three types of broad management objectives: water quality, conservation, and human use, to which the general public may easily relate. These will define the core and research indicators (WFD quality elements) to be used for monitoring; (b) priorities and optimisation in a (financially and logistically) resource constrained environment; (c) quality assurance; and (d) assessment of monitoring success: this should focus on the outputs, i.e. the internal audit of the monitoring activity, and on the outcomes. The latter component assesses programme effectiveness, i.e. environmental success based on a set of clearly-defined targets, and informs management action. The second part of this work discusses the approach and actions to be carried out for implementing WFD surveillance, operational and investigative monitoring. Appropriate spatial and temporal scales for surveillance monitoring of different indicators are suggested, and operational monitoring is classified into either screening or verification procedures, with an emphasis on the relationship between drivers, pressure, state and response. WFD investigative monitoring is interpreted as applied research, and thus guidelines cannot be prescriptive, except insofar as to provide examples of currently acceptable approaches. Specific case studies are presented for both operational (coastal eutrophication control) and investigative monitoring (harmful algal blooms), in order to illustrate the practical application of these monitoring guidelines. Further information is available at http://www.monae.org/ . PMID- 17342433 TI - Spatial distribution and transport of heavy metals in soil, ponded-surface water and grass in a pb-contaminated watershed as related to land-use practices. AB - The aim of this study was to investigate the spatial distribution of heavy metal in soil and evaluate the dissolution of metal from soil to ponded-surface water, leaching through soil profiles and metal uptake in grass as related to different land-use practices. The data provided a scientific basis for best-management practices for land use in Khli Ti watershed. The watershed has a Pb-contamination problem from the previous operation of a Pb-ore concentrator and abandoned Zn-Pb mine. Sampling sites were selected from a land-use map, with land-use types falling into the following four categories: forest, agricultural land, residential area and road. Soil, ponded-surface water, grass samples and soil profiles were collected. The study related soil characteristics from different land-use practices and locations with observed metal concentrations in ponded surface water and soil. High enrichment factors of Pb and As in soil were found. Partitioning coefficient, K(d) values were in the order: Cr > Pb > Ni > Cu > Cd > Zn. Soil disturbance from land-use activities including tillage and traffic increased leaching of trace metal from soils. Pb in soil was significantly taken up by grass even though the Transfer Factor, TF values were rather low. Agricultural activities in the watershed must be limited. Moreover, land encroachments in the upper and middle part of the watershed which have high potential of Pb must be strictly controlled in order to reduce the Pb contamination from non-point sources. PMID- 17342434 TI - Spatial concentration distributions of sulfur dioxide and nitrogen oxides in Patras, Greece, in a winter period. AB - An economic and quick methodology for performing a preliminary spatial assessment of a city air quality with the purpose to identify locations and zones susceptible to high pollution levels is proposed. A Patras case-study is selected, regarding the air pollutants of sulfur dioxide (SO(2)) and oxides of nitrogen (NO(x)). A total number of 451 samples of short duration, of which 225 were randomly picked in morning rush hours and 226 within evening rush hours, were collected from 50 locations of the major Patras area during a year period, when peaks of primary air pollutants usually occur. Concentration measurements at prescribed locations used to statistically calculate spatial average concentrations approximating 1-h mean values with mean probable errors less than 25.9% for SO(2), NO and NO(x) and less than 15.5% for NO(2). Then iso concentration contour diagrams plotted indicate high pollution zones and possibly appropriate locations for continuous or random monitoring according to the European Community (EC) Directives. The 1-h mean concentrations were in good correlation to the corresponding traffic rates and useful relationships are given (0.54 98% of incident light was absorbed within 2 m and zero photosynthetically active radiation (PAR) under 2 m in the estuarine stations during winter. Removal of heavy metals and nutrients by TSS in the water column was evident. Over 80% of the initial concentration of nutrients was removed within 10 min under various concentrations of TSS and also TSS contained significantly higher concentration of heavy metals than surface sediment. The concentration levels of nutrients and chemical oxygen demand in the west coast were comparable with the East and South Sea, even the major rivers in the Korean peninsula flow into the West Sea with major pollutant loadings into the coastal areas. High concentration of TSS is likely to contribute to the removal process of these pollutants, resulting in relatively lower levels of nutrients and organic materials in these coastal waters. PMID- 17342436 TI - Growth and biochemical parameters of Cicer arietinum L. grown on amended fly ash. AB - Growth and metal accumulation were investigated in two Cicer arietinum L. varieties (var. CSG-8962 and var. C-235) when grown in various combinations of fly ash (FA) amended with garden soil (GS), press mud (PM) or saw dust (SD). In addition, the levels of photosynthetic pigments, nitrate reductase (NR) activity, cysteine, non-protein thiols (NP-SH), and ascorbic acid were studied. FA amended with GS or PM led to a 5-10 times increase in biomass compared to FA control and was most pronounced in the less metal tolerant variety CSG-8962. Amendment of FA with either GS or PM only moderately increased the contents of some essential metals whereas the non-essential Cd and Cr remained similar or decreased slightly compared to FA control. FA combined with either GS or PM increased the amount of photosynthetic pigments and was largely absent when SD was added to FA. Improved nitrogen availability led to increased nitrate reductase (NR) activity with all amendments but less so with SD. Metal stress indicating parameters were generally reduced (cysteine and non-protein thiols) or unchanged (ascorbic acid). In conclusion, of the tested ameliorants both GS and PM greatly improved growth of C. arietinum making FA a suitable component of plant growth substrates. PMID- 17342437 TI - Heavy metal concentration in fish tissues inhabiting waters of "Busko Blato" reservoir (Bosnia and Herzegovina). AB - Heavy metals concentration (mercury, lead, cadmium, arsenic, copper, zinc and chromium) in tissues (muscles, liver, kidney and gonads) of Dalmatian barbelgudgeon, the nase, the souffie and brown trout, inhabiting waters of Busko Blato reservoir in Bosnia and Herzegovina, has been determined by atomic absorption spectrophotometry. The meat of the tested fish sorts does not contain elevated concentration of most analyzed heavy metals with exception of lead (higher than MAC in Italy, Germany and Denmark) and mercury (in muscles of brown trout higher than MAC in most countries). The lowest level of all heavy metals is always detected in gonads, with higher values in fry compared to milt for copper, zinc, chromium and arsenic. The highest copper concentration is observed in the liver from the souffie which is suggested as a suitable biomonitor for copper intoxication. In muscles of all fish sorts, lead was always present in much higher concentration than cadmium, while in kidneys of most fish sorts, lead and cadmium concentrations were similar. We showed that bioaccumulation of some heavy metals in the fish sorts analyzed is tissue and sex dependent. Also, we concluded that the small water exchange in reversible shallow reservoir does not induce elevated concentration of heavy metals in fish tissues inhabiting Busko Blato. PMID- 17342438 TI - Factors affecting river health and its assessment over broad geographic ranges: the Western Australian experience. AB - AusRivAS is an Australia-wide program that measures river condition using predictive models to compare the macroinvertebrate families occurring at a river site with those expected if the site were in natural condition. Results of assessment of 685 sites across all major rivers in Western Australia are presented. Most rivers were in relatively natural condition in the northern half of the state where the human population is low and pastoralism is the major land use. In the south, where the human population is higher and agriculture is more intensive, rivers were mostly more disturbed. AusRivAS assessment produced some erroneous results in rivers of the south-west cropping zone because of the lack of appropriate reference site groups and biased distribution of sampling sites. Collecting low numbers of animals from many forested streams, because of low stream productivity and samples that were difficult to sort, also affected assessments. Overall, however, AusRivAs assessment identified catchment processes that were inimical to river health. These processes included salinisation, high nutrient and organic loads, erosion and loss of riparian vegetation. River regulation, channel modification and fire were also associated with river degradation. As is the case with other assessment methods, one-off sampling at individual sites using AusRivAS may be misleading. Seasonal drought, in particular, may make it difficult to relate conditions at the time of sampling to longer-term river health. AusRivAS has shown river condition in Western Australia is not markedly different from other parts of Australia which, as a whole, lacks the substantial segments of severely degraded river systems reported in England. PMID- 17342439 TI - Organochlorine pesticides and polychlorinated biphenyl residues in reared and wild Dicentrarchus labrax from the Mediterranean Sea (Sicily, Italy). AB - The aim of this research was to compare the levels of organochlorine pesticides and PCBs in samples of Dicentrarchus labrax living in the Straits of Messina with samples cultivated in cages in the Mediterranean Sea. Muscles and liver tissues sampled over the months, within the same year, were analyzed. The quantitative determination of the organochlorine compounds was performed by GC-ECD and confirmed with GC-MS. The results showed that the concentrations of DDTs in muscles and livers as such of reared sea bass were in the range 0.2-1.3 microg/kg and 9.6 -48.4 microg/kg, respectively. In wild fish the concentrations of DDTs were very much lower: 0.1 microg/kg in muscles, 5.1-9.0 microg/kg in livers. Total PCBs levels were higher in cultivated sea bass than in wild fish; the concentration ranges were 5.3-59.7 microg/kg and 74.4-267.4 microg/kg in muscle and liver of reared samples, respectively, and 1.1-1.5 microg/kg and 63.2-109.4 microg/kg in muscle and liver of wild samples, respectively. PMID- 17342440 TI - Modified grey model for estimating traffic tunnel air quality. AB - This study compared three forecasting models based on the mean absolute percentage errors (MAPE) of their accuracy in forecasting air pollution in a traffic tunnel: the Grey model (GM), the combination model used four sample point and five sample point prediction with GM (1,1)(GM(1,1)(4 + 5)), and the modified grey model (MGM). An MGM was combined using the four points of the original sequence using the original grey prediction GM (1,1) for short-term forecasting. The proposed method cannot only enhance the prediction accuracy of the original grey model, but can also solve the jump data forecasting problem something for which the original grey model is inappropriate. The MAPE was applied to the models, and the MGM found the proposed method to be simple and efficient. The MAPE of MGM, calculated over 3 h of forecasts, were as follows: 10.12 (Upwind), 10.07 (Middle) and 7.68 (Downwind) for CO; 10.79 (Upwind), 6.05 (Middle) and 5.98 (Downwind) for NOx, and 11.67 (Upwind), 7.32 (Middle) and 4.56 (Downwind) for NMHC. The MGM model results reveal that the combined forecasts can significantly decrease the overall forecasting error. Results of this demonstrate that MGM can accurately forecast air pollution in the Kaohsiung Chung-Cheng Tunnel. PMID- 17342441 TI - Determination of heavy metals in water from boreholes in Dumasi in the Wassa West District of western region of Republic of Ghana. AB - Concentrations of heavy metals in the borehole at Dumasi in the Wassa West District of the Republic of Ghana have been measured in this study. The concentrations of the following metals in the ground water from Dumasi borehole are: Iron (Fe) - 7.52 ppm, Manganese (Mn) - 1.11 ppm, Arsenic (As) - 4.52 ppm, Chromium (Cr) - 0.026 ppm, Cobalt (Co) - 0.01 ppm, Zinc (Zn) - 0.007 ppm, Cadmium (Cd) - 0.002 ppm and Lead (Pb) - 0.005 ppm. The results of the study show that resident adults and children who use water from the boreholes are at serious risk from exposure to health hazards associated with exposure to the above metals in the boreholes in Dumasi. If the results of this study are applied to other mining communities, which lie on the Birimian and Tarkwaian rock system, then the residents are at serious risk from exposure to toxic metals from drinking water from the boreholes dag for them by mining companies operating in their communities. PMID- 17342442 TI - Evidence of chemical exchange in recombinant Major Urinary Protein and quenching thereof upon pheromone binding. AB - The internal dynamics of recombinant Major Urinary Protein (rMUP) have been investigated by monitoring transverse nitrogen-15 relaxation using multiple-echo Carr-Purcell-Meiboom-Gill (CPMG) experiments. While the ligand-free protein (APO rMUP) features extensive evidence of motions on the milliseconds time scale, the complex with 2-methoxy-3-isobutylpyrazine (HOLO-rMUP) appears to be much less mobile on this time scale. At 308 K, exchange rates k (ex) = 500-2000 s(-1) were typically observed in APO-rMUP for residues located adjacent to a beta-turn comprising residues 83-87. These residues occlude an entry to the binding pocket and have been proposed to be a portal for ligand entry in other members of the lipocalin family, such as the retinol binding protein and the human fatty-acid binding protein. Exchange rates and populations are largely uncorrelated, suggesting local 'breathing' motions rather than a concerted global conformational change. PMID- 17342443 TI - Drug information in Zimbabwe: 1990-1999. AB - OBJECTIVE: To assess the utilisation and development of the Zimbabwe Drug And Toxicology Information Service (DATIS) SETTING: The national drug and poisons information centre in Harare, Zimbabwe. METHOD: A survey of records at the Zimbabwe national Drug and Toxicology Information Service (DaTIS) for the period January 1990 to December 1999 was conducted and compared to a previous review. MAIN OUTCOME MEASURES: Average annual reporting rate, distribution of service users and report categories RESULTS: The mean (SD) reporting rate was 142.9 (81.6) p.a. with an increasing trend. Most contacts came from the capital city (67%). Pharmacists (40%) predominated in requests for drug information (DI), which comprised about three-quarters of reports, whereas toxicological enquiries mostly came from physicians (49%). Therapeutic categories mentioned most in DI reports were systemic anti-infective (24%) and nervous system agents (20.4%). Pesticides (28%) predominated in toxicology requests followed by pharmaceuticals (21%), largely nervous system (36%) and antiparasitic agents (23%). CONCLUSION: Compared to the previous decade, use of DaTIS had not grown significantly due to perceived resource constraints, lack of local political and institutional support and divided loyalty of staff. The drug and poison information components serves two distinct user populations with separate needs. Development plans for both DaTIS and other drug information services in Africa need to be realistic taking into account the resource constraints and local political and institutional support. PMID- 17342444 TI - Mifepristone in Italy: the case of a drug trapped between ethics and clinical practice. AB - In Italy mifepristone is not yet marketed. Gynaecologists in our hospital asked to use this medication as a less traumatic method for voluntary abortions. We followed the standard procedure defined by the Italian Health Ministry (IMH) for purchasing drugs from abroad but encountered several unexpected barriers. Starting from this case, this paper is aimed at identifying these barriers which we found to be not only professional, but also ethical, religious and moral. PMID- 17342445 TI - A tribute to Sir Jagadish Chandra Bose (1858-1937). AB - First, we provide a brief description of the life of Sir Jagadish Chandra Bose (1858-1937), his contemporaries, and some of his achievements. He is known for demonstrating the World's first wireless communication link at a wavelength of 5 mm. Then, we describe his contribution to photosynthesis research, as published in one of the earliest books on photosynthesis-a 1924 book entitled "Physiology of Photosynthesis." His pioneering work on photosynthesis preceded much of the future work in this area. In particular, we emphasize his work on Hydrilla that was a precursor to C-4 photosynthesis. PMID- 17342446 TI - Evaluating the relationship between leaf chlorophyll concentration and SPAD-502 chlorophyll meter readings. AB - Relationships between chlorophyll concentration ([chl]) and SPAD values were determined for birch, wheat, and potato. For all three species, the relationships were non-linear with an increasing slope with increasing SPAD. The relationships for birch and wheat were strong (r (2) approximately 0.9), while the potato relationship was comparatively weak (r (2) approximately 0.5). Birch and wheat had very similar relationships when the chlorophyll concentration was expressed per unit leaf area, but diverged when it was expressed per unit fresh weight. Furthermore, wheat showed similar SPAD-[chl] relationships for two different cultivars and during two different growing seasons. The curvilinear shape of the SPAD-[chl] relationships agreed well with the simulated effects of non-uniform chlorophyll distribution across the leaf surface and multiple scattering, causing deviations from linearity in the high and low SPAD range, respectively. The effect of non-uniformly distributed chlorophyll is likely to be more important in explaining the non-linearity in the empirical relationships, since the effect of scattering was predicted to be comparatively weak. The simulations were based on the algorithm for the calculation of SPAD-502 output values. We suggest that SPAD calibration curves should generally be parameterised as non-linear equations, and we hope that the relationships between [chl] and SPAD and the simulations of the present study can facilitate the interpretation of chlorophyll meter calibrations in relation to optical properties of leaves in future studies. PMID- 17342447 TI - A tribute to Per Halldal (1922-1986), a Norwegian photobiologist in Sweden. AB - We present here a tribute to Per Halldal (February 2, 1922-March 26, 1986), a leader, an instrumentalist, an expert on phototaxis in algae, and one whom we remember, even after 20 years of his death, as a person who spread joy, enthusiasm and knowledge wherever he went. PMID- 17342448 TI - Alterations in photosynthesis in Arabidopsis lacking IMMUTANS, a chloroplast terminal oxidase. AB - Green and white variegation in the Arabidopsis immutans (im) mutant is caused by a nuclear recessive gene. The green sectors contain cells with normal-appearing chloroplasts, while cells in the white sectors have photooxidized plastids lacking organized lamellae. In the present experiments, we found that the green im sectors have enhanced rates of carbon assimilation (monitored by (14)CO(2) uptake) and that there are corresponding increases in the activities of Rubisco and SPS, elevated starch and sucrose pool sizes, and an altered pattern of carbohydrate partitioning that favors sucrose over starch. We hypothesize that these increases are due, at least in part, to interactions with white sectors, perhaps to compensate for reductions in total source tissue. Consistent with this idea, the im white sectors accumulate low levels of sucrose and acid invertase activities are markedly increased in the white versus green cells. This suggests that there is a sucrose gradient between the green and white sectors, and that sucrose is transported from the green to white cells in response to sink demand. The expression of photosynthetic genes is not appreciably altered in the green im sectors versus wild type, but rather there is an up-regulation of genes involved in defense against oxidative stress and down-regulation of genes involved in cell wall biosynthesis. We postulate that changes in photosynthesis in the im green cells are driven by a need for photoprotection (especially early in chloroplast biogenesis) and due to source-sink interactions. PMID- 17342449 TI - Patient-reported sleep difficulty and cognitive function during the first year of dialysis. AB - BACKGROUND: Research in the general population indicates that sleep fragmentation is detrimental for cognitive function, but little attention has been given to this issue in dialysis patients. We hypothesized that patients with self-reported persistent sleep difficulty would have an increased risk of scoring lower on a cognitive function measure at follow-up compared to their score at baseline. METHODS: Sleep difficulty and cognitive function were reported by a large national patient cohort near the start of dialysis and at a 9- to 12-month follow up. Logistic regression was used to investigate the risk of scoring lower on a cognitive function measure at follow-up as a function of self-reported sleep difficulty, controlling for patients' sociodemographic, clinical and treatment characteristics, including depressed mood. RESULTS: At follow-up, cognitive function scores were lower among 35.8% of the cohort. Patients with self-reported persistent sleep difficulty had the lowest average cognitive function score. Men with reported persistent sleep difficulty, regardless of presence of depressed mood, had a significantly increased risk of a lower cognitive function score at follow-up. Women with reported persistent sleep difficulty as well as depressed mood had significantly increased risk of a lower cognitive function score. CONCLUSION: The potential impact of sleep difficulty and depressed mood on the cognitive function of dialysis patients emphasizes the importance of evaluating and treating these risks and highlights the value of continued research to improve our understanding and management of these issues. PMID- 17342450 TI - Recent advances in newborn screening. AB - The introduction of tandem mass spectrometry has unquestionably been the most striking recent advance in newborn screening. A single test is applied for the simultaneous diagnosis of a number of disorders, making it possible to screen for some disorders that might otherwise have seemed too rare. Current screening is for disorders of metabolism of amino acids, organic acids and fatty acids. Assay performance for detection of disorders appears very good, but rarity of disorders, varied definitions and systems for follow-up and lack of databases for inborn errors of metabolism diagnosed clinically means that there is as yet insufficient information about most disorders. The technology can be applied to a much wider range of compounds, and the field looks set to expand. A key feature of newborn screening programmes must be the assessment of outcomes, and a major reason for the lack of uniformity in the approach adopted in different countries is the paucity of information on this. The available evidence points to overall advantages flowing from early diagnosis by screening, with reduction in mortality and morbidity. More studies are clearly needed and some are under way. The next new group of disorders already proposed for newborn screening is the lysosomal storage disorders. Attitudes may be changing about what it is desirable to include in a newborn screening programme, and this will indeed pose new ethical dilemmas. PMID- 17342451 TI - Cardiovascular and respiratory hospitalizations and mortality among users of tiotropium in Denmark. AB - Tiotropium (Spiriva is an inhaled, once-daily anticholinergic medication for chronic obstructive pulmonary disease (COPD). We conducted a population-based cohort study to examine the risk of cardiovascular and respiratory hospitalizations and mortality with tiotropium. Using the Danish healthcare registries, we identified persons >/=40 years old in three counties who were hospitalized for COPD from 1/1/1977 to 12/31/2003. Respiratory and cardiovascular medications were assessed from dispensing records. Cox regression was used to compute incidence rate ratios (RR) and 95% confidence intervals (CI) for hospitalization and death between 1/1/2002 and 12/31/2003, associated with periods of tiotropium use compared to non-use, controlling for age, gender, time since COPD, concomitant respiratory and cardiovascular medications, prior hospitalizations and Charlson comorbidity index. Among persons with COPD (10,603), 75% were >/=60 years old. Follow-up was >/=18 months for 64%. Among those exposed to tiotropium compared to periods of non-use, the RR for total and cause-specific hospitalization endpoints were not elevated except for COPD hospitalization (RR = 1.52, 95% CI: 1.29, 1.79). Mortality endpoints included total mortality (RR = 0.77, 95% CI: 0.65, 0.91), respiratory mortality (RR = 0.79, 95% CI: 0.60, 1.04), sudden death (RR = 0.71, 95% CI: 0.21, 2.34), cardiac arrest (RR = 0.74, 95% CI: 0.42, 1.32), heart failure (RR = 0.84, 95% CI: 0.41, 1.75), and myocardial infarction (RR = 1.25, 95% CI: 0.49, 3.17). Compared to periods of non-use, tiotropium was associated with reduced respiratory and overall mortality and was not associated with increased cardiac mortality. An increase in COPD hospitalization is inconsistent with clinical trial data and suggests preferential prescribing due to disease severity. PMID- 17342452 TI - The solution structure of the core of mesoderm development (MESD), a chaperone for members of the LDLR-family. AB - Mesoderm development (MESD) is a 224 amino acid mouse protein that acts as a molecular chaperone for receptors of the low-density lipoprotein receptor (LDLR) family. By recording (15)N-HSQC-NMR spectra of six different MESD constructs, we could determine a highly structured core region corresponding to residues 104 177. Here we firstly present the solution structure of this highly conserved core of MESD. It shows a four-stranded anti-parallel beta-sheet and two alpha-helices situated on one side of the sheet. Although described in the literature as structurally homologues to ferredoxins, the connectivity of secondary structure elements is different in the MESD fold. A structural comparison to entries of the PDB reveals a frequent domain with low sequence homology annotated as HMA and P II domains in Pfam. PMID- 17342453 TI - Structural basis of CoA recognition by the Pyrococcus single-domain CoA-binding proteins. AB - The single-domain coenzyme A (CoA)-binding protein is conserved in bacteria, archaea, and a few eukaryal taxa. It consists of a Rossmann-fold domain, belonging to the FAD/NAD(P)-binding ;superfamily. The crystal structure of the Thermus thermophilus single-domain CoA-binding protein, TTHA1899, has been determined and it has been demonstrated, by isothermal titration calorimetry, that the protein interacts with CoA [Wada T. et al. Acta Crystallogr D Biol Crystallogr 59 (2003) 1213]. In the present study, we determined the crystal structures of an orthologous protein from the archaeon Pyrococcus horikoshii (PH1109), alone and complexed with CoA, at 1.65 A and 1.70 A resolutions, respectively, and that of P. furiosus protein (PF0725) in the CoA-bound form at 1.70 A. The CoA-bound structures are very similar to each other, revealing that the Pyrococcus proteins bind CoA in a 1:1 stoichiometry. Five loop-containing regions form the CoA-binding groove, to which the CoA molecule is docked. A comparison of the structures and the sequences of the Pyrococcus proteins with those of the T. theromphilus orthologue TTHA1899 indicated that archaeal and bacterial single-domain CoA-binding proteins share the same CoA-binding mode. Nevertheless, many of the peripheral residues involved in the hydrogen bonding/electrostatic interactions with CoA are not strictly conserved in the family. The CoA interaction of the single-domain CoA-binding proteins is significantly different and much more extensive than that of the multi subunit/multi-domain CoA-binding protein succinyl-CoA synthetase. PMID- 17342454 TI - Quality-of-life outcome after hallux valgus surgery. AB - OBJECTIVE: To assess the quality of life before and after hallux valgus surgery. METHODS: A longitudinal study with 94 consecutive patients undergoing hallux valgus surgery. Assessments were made preoperatively and at 12 month postoperatively. Measures used were the quality of life (QoL) according to SF-36, a disease specific score (the American Orthopaedic Foot and Ankle Society's clinical rating system for the hallux), the severity of the deformity, the possibility of wearing the preferred choice of shoes and satisfaction with the treatment. The pre- and postoperative QoL scores were compared with the score in the general population. RESULTS: QoL outcomes improved significantly postoperatively regarding bodily pain, vitality, mental health and the mental component summary. The correction of the deformity did not affect the QoL. Regardless of the extent of correction, the choice of shoeware and the degree of satisfaction with surgery were associated with a better QoL. CONCLUSIONS: Hallux valgus patients have worse pain than the general population. Surgery produces a significant improvement in the quality of life. The severity of the deformity did not influence the QoL, however; the free choice of shoeware and the degree of satisfaction with the surgery had a positive effect on the QoL outcome. SF-36 is a relevant tool for evaluating outcome in hallux valgus surgery. PMID- 17342455 TI - Development and evaluation of a computer adaptive test for 'Anxiety' (Anxiety CAT). AB - Within the framework of item response theory (IRT), we developed a German version of an item bank, as well as a software application that can be employed to measure anxiety by means of a computer adaptive test (CAT). A sample of n = 2348 psychiatric and psychosomatic patients answered a set of up to 13 standardized questionnaires. 81 items drawn from these questionnaires were considered pertinent to the anxiety construct. Various tests were conducted to ensure the suitability of these items for an IRT-based assessment. After these tests, 50 items remained in the item bank and were calibrated using the Generalized Partial Credit Model. Simulation studies conducted on an independent sample of n = 1528 respondents indicate that 6-8 items suffice to measure the latent trait with high precision (standard error T), peroxisome proliferator activated receptor, gamma 2 (PPARG Pro12Ala), PPARG-coactivator, 1 alpha (PPARGC1A Gly482Ser), forkhead box C2 (FOXC2 -512C > T) and beta3 adrenergic receptor (ADRB3 Trp64Arg) polymorphisms using TaqMan allelic discrimination assay or RFLP. RESULTS: The CC, CT and TT genotype frequencies of the TCF7L2 rs7903146 variant differed significantly between women with gestational diabetes mellitus and control women (46.3, 43.6 and 10.1% vs 58.5, 35.3 and 6.2%, p = 3.7 x 10(-6), corrected p value [Pc] for multiple testing Pc = 2.2 x 10(-5)). The T-allele was associated with an increased risk of gestational diabetes mellitus (odds ratio 1.49 [95% CI 1.28-1.75], p = 4.9 x 10(-7) [Pc = 2.8 x 10(-6)]). Compared with wild-type CC-genotype carriers, heterozygous (CT genotype) and homozygous (TT-genotype) carriers had a 1.6-fold (95% CI 1.26-1.93, p = 3.7 x 10(-5) [Pc = 0.0002]) and a 2.1-fold (95% CI 1.41-2.99, p = 0.0001 [Pc = 0.0008]) increased risk of gestational diabetes mellitus, respectively. The other polymorphisms studied were not significantly associated with gestational diabetes mellitus (ADIPOQ +276G > T: 1.17 [1.01-1.36], p = 0.039 [Pc = 0.23]; PPARG Pro12Ala: 1.06 [0.87-1.29], p = 0.53; PPARGC1A Gly482Ser: 0.96 [0.83-1.10], p = 0.54; FOXC2 -512C > T: 1.01 [0.87-1.16], p = 0.94; and ADRB3 Trp64Arg: 1.22 [0.95-1.56], p = 0.12). CONCLUSIONS/INTERPRETATION: The TCF7L2 rs7903146 variant is associated with an increased risk of gestational diabetes mellitus in Scandinavian women. PMID- 17342474 TI - A triazolam/amphetamine dose-effect interaction study: dissociation of effects on memory versus arousal. AB - RATIONALE: In addition to producing robust memory impairment, benzodiazepines also induce marked sedation. Thus, it is possible that the observed amnestic effects are secondary to more global sedative effects and do not reflect a specific primary benzodiazepine effect on memory mechanisms. OBJECTIVE: The objective was to use the nonspecific stimulant d-amphetamine to dissociate the sedative and memory-impairing effects of the benzodiazepine triazolam. MATERIALS AND METHODS: Single oral doses of placebo, triazolam alone (0.25, 0.50 mg/70 kg), d-amphetamine sulfate alone (20, 30 mg/70 kg), and triazolam (0.25, 0.50 mg/70 kg) and d-amphetamine sulfate (20, 30 mg/70 kg) conjointly (at all dose combinations) were administered to 18 healthy adult participants across nine sessions in a double-blind, staggered-dosing, crossover design. In addition to standard data analyses, analyses were also conducted on z-score standardized data, enabling effects to be directly compared across measures. RESULTS: Relative to the sedative measures, the memory measures generally exhibited a pattern of less reversal of triazolam's effects by d-amphetamine. The memory measures ranged in degree of reversal such that the most reversal was observed for reaction time on the n-back working memory task, and the least reversal was observed for accuracy on the Sternberg working memory task, with most measures showing an overall pattern of partial reversal. CONCLUSIONS: Benzodiazepines have specific effects on memory that are not merely a by-product of the drugs' sedative effects, and the degree to which sedative effects contribute to the amnestic effects varies as a function of the particular memory process being assessed. PMID- 17342475 TI - Involvement of the head and trunk during gaze reorientation during standing and treadmill walking. AB - As individuals stand or walk in an environment their gaze may be reoriented from one location to another in response to auditory or visual stimuli. In order to reorient gaze, the eyes and/or the head and trunk must rotate. However, what determines the exact degree of rotation of each segment while standing or walking is not fully understood. In the current study we show that when participants were asked to reorient their gaze towards light cues positioned at eccentric locations of up to 90 degrees while standing or walking on a treadmill their eyes and head mainly facilitated the action. Rotations of the head-in-space were similar for both tasks, but the rotation of the shoulders- and hips-in-space were lower for the treadmill walking condition. It is argued that this difference in the level of head-on-trunk rotation during the two tasks is controlled by the vestibular feedback loop. The regulation of this feedback loop is performed by the cerebellum in response to the level of threat to postural stability. PMID- 17342476 TI - Fatigue-induced changes of impedance and performance in target tracking. AB - Kinematic variability is caused, in part, by force fluctuations. It has been shown empirically and numerically that the effects of force fluctuations on kinematics can be suppressed by increasing joint impedance. Given that force variability increases with muscular fatigue, we hypothesized that joint impedance would increase with fatigue to retain a prescribed accuracy level. To test this hypothesis, subjects tracked a target by elbow flexion and extension both with fatigued and unfatigued elbow flexor and extensor muscles. Joint impedance was estimated from controlled perturbations to the elbow. Contrary to the hypothesis, elbow impedance decreased, whereas performance, expressed as the time-on-target, was unaffected by fatigue. Further analysis of the data revealed that subjects changed their control strategy with increasing fatigue. Although their overall kinematic variability increased, task performance was retained by staying closer to the center of the target when fatigued. In conclusion, the present study reveals a limitation of impedance modulation in the control of movement variability. PMID- 17342477 TI - Error correction in bimanual coordination benefits from bilateral muscle activity: evidence from kinesthetic tracking. AB - Although previous studies indicated that the stability properties of interlimb coordination largely result from the integrated timing of efferent signals to both limbs, they also depend on afference-based interactions. In the present study, we examined contributions of afference-based error corrections to rhythmic bimanual coordination using a kinesthetic tracking task. Furthermore, since we found in previous research that subjects activated their muscles in the tracked (motor-driven) arm, we examined the functional significance of this activation to gain more insight into the processes underlying this phenomenon. To these aims, twelve subjects coordinated active movements of the right hand with motor-driven oscillatory movements of the left hand in two coordinative patterns: in-phase (relative phase 0 degrees) and antiphase (relative phase 180 degrees). They were either instructed to activate the muscles in the motor-driven arm as if moving along with the motor (active condition), or to keep these muscles as relaxed as possible (relaxed condition). We found that error corrections were more effective in in-phase than in antiphase coordination, resulting in more adequate adjustments of cycle durations to compensate for timing errors detected at the start of each cycle. In addition, error corrections were generally more pronounced in the active than in the relaxed condition. This activity-related difference was attributed to the associated bilateral neural control signals (as estimated using electromyography), which provided an additional reference (in terms of expected sensory consequences) for afference-based error corrections. An intimate relation was revealed between the (integrated) motor commands to both limbs and the processing of afferent feedback. PMID- 17342478 TI - Perception of limb orientation in the vertical plane depends on center of mass rather than inertial eigenvectors. AB - We performed two experiments to test the hypothesis that the perception of limb orientation depends on inertial eigenvectors (e(i)) against the alternative hypothesis that it depends on the center of mass vector (CM). Whereas e(i) constrains the dynamic torques involved in angular rotation, CM constrains the static torque necessary to keep the limb aloft in the gravitational field. Hence, possible effects of e(i) and CM on kinesthetic judgments must be related to the dynamic and static torques, respectively, involved in moving and positioning a limb. In the first experiment, blindfolded participants matched, with upper arms supported, the orientation of their forearms while the forearms' e(i) and CM were manipulated relative to the elbow. The manipulation of the vector CM alone induced a matching bias, as did the combined manipulation of e(i) and CM, whereas the manipulation of e(i) alone did not. In the second experiment, participants positioned their unseen and unsupported right arm at an indicated spatial configuration while e(i) and CM of the right forearm were manipulated as in Experiment 1. As in the first experiment, forearm positioning was affected by the independent manipulation of CM and the combined manipulation of e(i) and CM, but not by the independent variation of e(i). Moreover, none of the manipulations affected upper arm positioning. These results refute the claim that the perception of limb orientation (in the vertical plane) is based on e(i)and demonstrate, for the first time, the implication of a limb segment's CM in the perception of its orientation. PMID- 17342479 TI - Postural control anomalies in children with Tourette syndrome. AB - The goal of the present study was to determine whether postural control is affected in Gilles-de-la-Tourette syndrome (TS). Center of pressure (COP) displacements were recorded in children with TS and unaffected siblings in three conditions using a force platform: (1) Eyes-Open, (2) Eyes-Closed, (3) One-Leg standing with eyes open. The COP range and velocity were higher in children with TS than in unaffected siblings in all conditions. These differences could not be attributed to age, present tic severity, comorbidities (hyperactivity and compulsions) or medication. The data suggest that sub-clinical postural control anomalies are present in TS. PMID- 17342480 TI - Pharmacokinetic study of the interaction between itraconazole and nevirapine. AB - OBJECTIVE: To investigate the drug interaction potential between itraconazole and nevirapine. METHODS: Our study was conducted in 12 healthy volunteers in two phases. In phase 1 (from days 1-28), all subjects were randomly assigned to a two way crossover study of a nevirapine regimen (nevirapine 200 mg once daily for 7 days) and an itraconazole regimen (itraconazole 200 mg once daily for 7 days) with a 14-day wash-out period between. Phase 2 (from days 43-49) was performed 14 days after phase 1 ended, and all subjects received a combination regimen (nevirapine 200 mg combined with itraconazole 200 mg once daily for 7 days). Nevirapine pharmacokinetic studies were carried out starting with the seventh dose of nevirapine in the nevirapine regimen (on days 7-10 or 28-31) and the combination regimen (on days 49-52). Itraconazole pharmacokinetic studies were carried out starting with the seventh dose of itraconazole in the itraconazole regimen (on days 7-10 or 28-31) and the combination regimen (on days 49-52). RESULTS: There was no significant difference in nevirapine pharmacokinetic parameters between the nevirapine and combination regimens. Itraconazole plasma concentrations were lower when it was administered in the combination regimen than when it was administered in the itraconazole regimen. The mean C(max), AUC(0 96) and t (1/2) of itraconazole were significantly reduced by 38, 61 and 31%, respectively. CONCLUSION: Nevirapine had a strong inducing effect on the metabolism of itraconazole, but there was no significant effect of itraconazole on the pharmacokinetics of nevirapine. However, a higher daily dosage of itraconazole might have an inhibitory effect. PMID- 17342481 TI - Placental transfer of bupivacaine enantiomers in normal pregnant women receiving epidural anesthesia for cesarean section. PMID- 17342482 TI - Accordion effect during carotid artery stenting: report of two cases and review of the literature. AB - INTRODUCTION: The term "accordion effect" is used to describe a mechanical distortion of tortuous arteries mimicking spasm or dissection. This phenomenon has been reported in patients undergoing percutaneous coronary intervention. To our knowledge, this is the first documentation of the accordion effect during carotid artery intervention. METHODS: Two patients who developed the accordion effect during carotid artery stenting (CAS) are described. RESULTS: Angiograms obtained just after CAS showed a stenosing lesion with wall irregularity at the distal part of the stent. This lesion disappeared and tortuosity of the internal carotid artery developed after withdrawing the guidewire until its floppy segment rested equally on the lesion. In another patient, the lesion did not disappear completely until the guiding catheter had been withdrawn to the proximal portion of the common carotid artery. We conclude that these stenosing lesions reflected the accordion effect. CONCLUSION: It is essential to differentiate the accordion effect from dissection, spasm, and thrombosis because the management is importantly different. We report our findings and present a review of the literature. PMID- 17342483 TI - Expression profile of novel members of the rat mast cell protease (rMCP)-2 and (rMCP)-8 families, and functional analyses of mouse mast cell protease (mMCP)-8. AB - Four hematopoietic serine proteases are common to the mast cell chymase locus of all analyzed mammals: alpha-chymase, cathepsin G, granzyme B, and granzyme C/H. Apart from these common genes, the mouse and rat loci hold additional granzyme-, beta-chymase-, and Mcpt8-like genes. To better understand the functional consequences of these additional enzymes and to be able to compare human and rodent immune functions, we have analyzed the expression of novel beta-chymase- and Mcpt8-like genes in the rat. Four novel genes, i.e., Mcpt2-rs2a, Mcpt2-rs2c, Mcpt8-rs1, and Mcpt8-rs4 were transcribed in tissues holding mucosal mast cells (MMC), where also the classical MMC protease Mcpt2 was expressed. We also found transcripts of rat vascular chymase (rVch) in some of these tissues. RVch is a beta-chymase that converts angiotensin I, like the human chymase. Rat MMC may therefore have similar angiotensin-converting properties as chymase-positive human mast cells, although these are mostly regarded the counterpart of rat connective tissue mast cells. The human mast cells that are considered the counterpart of rat MMC express, however, only tryptase, whereas rat MMC express various proteases, but no tryptase. We further studied the proteolytic activity of mMCP-8 as a first representative for the Mcpt8-subfamily. Based on sequence comparison and molecular modeling, mMCP-8 may prefer aspartic acid in substrate P1 position. However, we could not detect hydrolysis of chromogenic substrates or phage-displayed random nonapeptides despite numerous trials. On the other hand, we have obtained evidence that the function of the Mcpt8-like proteases depends on proteolytic activity. Namely, the expression of the only Mcpt8-family member with a mutation in the catalytic triad, Mcpt8-rs3, was strongly reduced. Thus, the substrate specificity of mMCP-8 may be too narrow to be detected with the employed methods, or the enzyme may require a substrate conformation that is not provided by the analyzed peptides. PMID- 17342484 TI - Perfusion scintigraphy: diagnostic utility in pregnant women with suspected pulmonary embolic disease. AB - Pulmonary embolism (PE) is a major preventable cause of maternal mortality during pregnancy and accurate diagnosis is essential. Computed tomography pulmonary angiography (CTPA) is a robust diagnostic test in non-pregnant patients with suspected PE. The potential latent carcinogenic effects of CTPA-related breast irradiation mandates careful use of this technique in young women. The aim of this study was to determine the efficacy of perfusion scintigraphy as the first line investigation in pregnant women with suspected PE. All pregnant women referred for radiological investigation of suspected PE in a 5-year period from January 2001 to December 2005 were included. Demographic data and imaging studies were reviewed. Subsequent pregnancy outcome was determined by case note review. One hundred and five consecutive patients had either perfusion scintigraphy (Q scan) (n = 94), CTPA (n = 9) or both (n = 2), one patient presented twice. Q scans were the first line investigation in 96 (91%) patients. Eighty-nine (92%) scans were normal, seven (7%) were non-diagnostic and one (1%) was high probability. One patient had a thromboembolic event 3 weeks post partum. No adverse events were reported during the follow-up period. Pulmonary embolic disease is uncommon in pregnancy. Perfusion scintigraphy in pregnant patients has an excellent diagnostic yield. The percentage of non-diagnostic scans is much lower than in other patient groups. Scintigraphy imparts a significantly lower breast dose than CTPA and should be used as the first-line investigation in most pregnant patients with suspected PE. PMID- 17342485 TI - Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection. AB - A prospective study was performed to determine the value of sonoelastography (SE) targeted biopsy for prostate cancer (PCa) detection. A series of 230 male screening volunteers was examined. Two independent examiners evaluated each subject. One single investigator performed < or =5 SE targeted biopsies into suspicious regions in the peripheral zone only. The stiffness of the lesion was displayed by SE and color-coded from red (soft) to blue (hard). Hard lesions were considered as malignant and targeted by biopsy. Subsequently, another examiner performed ten systematic biopsies. Cancer detection rates of the two techniques were compared. Cancer was detected in 81 of the 230 patients (35%), including 68 (30%) by SE targeted biopsy and in 58 (25%) by systematic biopsy. Cancer was detected by targeted biopsy alone in 23 patients (10%) and by systematic biopsy alone in 13 patients (6%). The detection rate for SE targeted biopsy cores (12.7% or 135 of 1,109 cores) was significantly better than for systematic biopsy cores (5.6% or 130 of 2,300 cores, P < 0.001). SE targeted biopsy in a patient with cancer was 2.9-fold more likely to detect PCa than systematic biopsy. SE targeted biopsy detected more cases of PCa than systematic biopsy, with fewer than half the number of biopsy cores in this prostate-specific antigen screening population. PMID- 17342486 TI - Investigation of normal organ development with fetal MRI. AB - The understanding of the presentation of normal organ development on fetal MRI forms the basis for recognition of pathological states. During the second and third trimesters, maturational processes include changes in size, shape and signal intensities of organs. Visualization of these developmental processes requires tailored MR protocols. Further prerequisites for recognition of normal maturational states are unequivocal intrauterine orientation with respect to left and right body halves, fetal proportions, and knowledge about the MR presentation of extrafetal/intrauterine organs. Emphasis is laid on the demonstration of normal MR appearance of organs that are frequently involved in malformation syndromes. In addition, examples of time-dependent contrast enhancement of intrauterine structures are given. PMID- 17342487 TI - The role of MR imaging in the diagnostic characterisation of appendicular bone tumours and tumour-like conditions. AB - MRI has an established role in the local staging of primary bone tumours. However, as the majority of tumours have non-specific appearances on MRI, the diagnosis is usually established on the basis of clinical history, plain film findings and biopsy. This article reviews the value of MRI in the further characterisation of appendicular bone tumours and tumour-like lesions, with particular reference to peri-lesional oedema, fluid-fluid levels, flow voids, fat signal, cartilage signal and dedifferentiation. These features are a useful adjunct for distinguishing between benign and malignant disease, pointing towards a more specific diagnosis, and guiding biopsy. PMID- 17342488 TI - Delineation of temporal bone anatomy: feasibility of low-dose 64-row CT in regard to image quality. AB - The aim of our present study was to evaluate the visualization of anatomical landmarks of the temporal bone using a low-dose 64-slice computed tomography (CT) technique. A total of 120 patients were evaluated, 60 patients (mean age 47.1 years; 36 male, 24 female) underwent examination with a 4-slice CT scanner: 180 mAs, 120 kV, 1 s rotation time, 2 x 0.5 mm collimation, 0.5 mm slice thickness. Another 60 consecutive patients (mean age 37.4 years; 43 male, 37 female) were examined using a 64-slice CT low-dose protocol: 140 mAs, 120 kV, 1 s rotation time, 12 x 0.6 mm collimation, 0.6 mm slice thickness. The visibility of 42 landmarks was scored by two blinded radiologists using a five-point quality rating scale. Mean equivalent dose was significantly lower for the 64-slice CT protocol (0.31 mSv +/- 0.12 mSv) compared to the 4-slice CT protocol (0.61 mSv +/ 0.08 mSv). Despite increased image noise, only 19% of the anatomical landmarks were delineated significantly better on the axial sections of the 4-slice CT and only 9.5% of the anatomical landmarks on the reformatted coronal images. The interobserver agreement did not differ significantly between the two modalities. Low-dose 64-slice CT technique facilitates temporal bone imaging with sufficient anatomical detail. PMID- 17342489 TI - Treatment of localized prostate cancer. PMID- 17342490 TI - Biopsy standards for detection of prostate cancer. AB - The widespread use of measurement of prostate-specific antigen for prostate cancer screening has led to a dramatic increase in the number of transrectal biopsies. Although transrectal ultrasound-guided prostate biopsy is the gold standard in the diagnosis of prostate cancer, the strategies for initial and repeat biopsies remain controversial. Over the past decade numerous biopsy protocols have been developed. Several protocols have been established that increase the number of cores by combining sextant and lateral biopsies to increase the cancer detection rate. We review the current methods of prostate biopsies, the indication to perform an initial and repeat biopsy, the impact of prostate volume on the number of cores taken, and the morbidity of the procedure. PMID- 17342491 TI - Efficient inhibition of bursts by bursts in the auditory system of crickets. AB - In crickets, auditory information about ultrasound is carried bilaterally to the brain by the AN2 neurons. The ON1 neuron provides contralateral inhibitory input to AN2, thereby enhancing bilateral contrast between the left and right AN2s, an important cue for sound localization. We examine how the structures of the spike trains of these neurons affect this inhibitory interaction. As previously shown for AN2, ON1 responds to salient peaks in stimulus amplitude with bursts of spikes. Spike bursts, but not isolated spikes, reliably signal the occurrence of specific features of the stimulus. ON1 and AN2 burst at similar times relative to the amplitude envelope of the stimulus, and bursts are more tightly time-locked to stimulus feature than the isolated spikes. As a consequence, spikes that, in the absence of contralateral inhibition, would occur within AN2 bursts are more likely to be preceded by spikes in ON1 (mainly also in bursts) than are isolated AN2 spikes. This leads to a large decrease in the burst rate of the inhibited AN2. We conclude that the match in coding properties of ON1 and AN2 allows contralateral inhibition to be most efficient for those portions of the response that carry the behaviourally relevant information, i.e. for bursts. PMID- 17342492 TI - Mechanisms of vasodilation in the dorsal aorta of the elephant fish, Callorhinchus milii (Chimaeriformes: Holocephali). AB - This study investigated vasodilator mechanisms in the dorsal aorta of the elephant fish, Callorhinchus milii, using anatomical and physiological approaches. Nitric oxide synthase could only be located in the perivascular nerve fibres and not the endothelium of the dorsal aorta, using NADPH histochemistry and immunohistochemistry. In vitro organ bath experiments demonstrated that a NO/soluble guanylyl cyclase (GC) system appeared to be absent in the vascular smooth muscle, since the NO donors SNP (10(-4) mol l(-1)) and SIN-1 (10(-5) mol l(-1)) were without effect. Nicotine (3 x 10(-4) mol l(-1)) mediated a vasodilation that was not affected by ODQ (10(-5) mol l(-1)), L-NNA (10(-4) mol l(-1)), indomethacin (10(-5) mol l(-1)), or removal of the endothelium. In contrast, the voltage-gated sodium channel inhibitor, tetrodotoxin (10(-5) mol l( 1)), significantly decreased the dilation induced by nicotine, suggesting that it contained a neural component. Pre-incubation of the dorsal aorta with the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP(8-37) (10(-6) mol l(-1)) also caused a significant decrease in the nicotine-induced dilation. We propose that nicotine is mediating a neurally-derived vasodilation in the dorsal aorta that is independent of NO, prostaglandins and the endothelium, and partly mediated by CGRP. PMID- 17342494 TI - Transvaginal ultrasound-guided aspiration and instillation of hyperosmolar glucose for treatment of unruptured tubal heterotopic pregnancy. AB - OBJECTIVES: To report a case of tubal heterotopic pregnancy (HP) treated conservatively with transvaginal ultrasound-guided aspiration and instillation of hyperosmolar glucose. METHODS: Aspiration of the tubal ectopic pregnancy and hyperosmolar glucose instillation was performed with a 16-gauge needle under transvaginal ultrasound guidance. RESULTS: Unruptured tubal HP with positive cardiac activity was treated successfully without any further interventions, and intrauterine pregnancy has reached full-term without any complications. CONCLUSIONS: Early diagnosis of this life-threatening condition is the key to its successful treatment. Transvaginal ultrasound-guided aspiration and hyperosmolar glucose injection can be safely performed for the treatment of unruptured tubal HP. PMID- 17342493 TI - High definition mapping of circular and longitudinal motility in the terminal ileum of the brushtail possum Trichosurus vulpecula with watery and viscous perfusates. AB - Longitudinal and radial movements during spontaneous contractions of isolated segments of terminal ileum of the brushtail possum, a species of arboreal folivore, were studied using high definition spatiotemporal maps. Segments obtained from specimens were continuously perfused with solutions of various apparent viscosities at 3 cm and 5 cm hydrostatic pressure. A series of sustained tetrodotoxin-sensitive peristaltic events occurred during perfusion. The leading edge of each peristaltic event progressed by a succession of rhythmic surges of circular contraction with concerted concurrent phasic longitudinal contractions. Three types of peristaltic event were observed, with differing durations of occlusion and patterns of cyclic, in phase, circular and longitudinal contractions. Each peristaltic event was preceded by a change of shade on the D map that indicated circumferential dilatation. Differences in the slopes of these phasic shade changes from those occurring during peristalsis indicate that this distension is passive and likely results from aboral displacement of fluid. Tetradotoxin insensitive longitudinal contraction waves of frequency 9.2 min(-1) occurred during and in the absence of peristalsis, originating at a variety of sites, and propagating either in an orad or aborad direction but predominantly in the latter. Perfusion with 1% guar gum, at 5 cm hydrostatic pressure caused the lumen to become distended and the generation of peristaltic events to cease pending reduction of the hydrostatic head to 3 cm but longitudinal contractile activity was preserved. Neither the frequencies nor the rates of progression of circular and longitudinal contractile events, nor the temporal coordination between these events, varied with the apparent viscosity of the perfusate or altered in a manner that could facilitate mixing. PMID- 17342496 TI - The relationship between fetal gender and pregnancy outcome. AB - BACKGROUND: Genesis 3:16 is the passage usually quoted by those who believe women have been cursed to give birth in pain. God punished Eve that she will have increased (painful) labor, after she was beguiled by the serpent and ate the forbidden fruit of knowledge. The Lord God said "I will greatly multiply your pain in childbearing; in pain you shall bring forth children". Nevertheless, the word translated as "children" is the Hebrew word "banim" which means "boys". Indeed, most interpreters translated boys as children. Yet, there is gaining scientific evidence that the gender does matter. OBJECTIVE: The present Editorial will discuss gender differences in perinatal medicine. CONCLUSIONS: Male gender is an independent risk factor for adverse pregnancy outcome. Further research including endocrine and immunological tests is needed to clarify gender differences in birth outcome. PMID- 17342495 TI - Are nuchal translucency, pregnancy associated plasma protein-A or free-beta-human chorionic gonadotropin depending on maternal age? A multicenter study of 8,116 pregnancies. AB - INTRODUCTION: First-trimester screening according to Nicolaides uses maternal age to obtain a common background risk for trisomy 21. The likelihood ratios by nuchal translucency, free beta-human chorionic gonadotropin and pregnancy associated plasma protein-A are not with respect to maternal age. It was the aim of this study to investigate if likelihood ratios should better take care of it. MATERIALS: Pearson's correlation and different models of regression analysis had been performed on the results of 8,116 first-trimester screenings. The total number of pregnancies was subdivided into three subgroups of healthy fetuses (n = 8,038); fetuses with Down's syndrome (n = 46) and fetuses with other genetic abnormalities (n = 32). Statistical testing was applied to each of the three groups. RESULTS: Strong independence from maternal age could be found for each of the first-trimester screening measurement parameter, as well for healthy and as for affected fetuses. Neither Pearson's test nor nonlinear regression models could detect a correlation. Accordingly significance of Pearson's test is not given. DISCUSSION: First-trimester screening would not be improved by considering the maternal age in the calculation of the likelihood ratios. Therefore the currently used algorithm is adequate. According, to the results, it seems to be proper as well to disregard the maternal age in newer test strategies advanced first-trimester screening (AFS) at all. PMID- 17342497 TI - Modern intrapartum fetal monitoring: room for improvement? PMID- 17342498 TI - Characterization of therapy and costs for patients with uterine fibroids in Utah Medicaid. AB - OBJECTIVES: To determine in an eligible Utah Medicaid population (1) medical and drug costs associated with treating uterine fibroids (UFs) and (2) the cost and incidence of hysterectomy complications. METHODS: Medical and drug cost analyses were based on data from 897 premenopausal patients with UFs included in the Utah Medicaid database from 1996 to 2004. UF-related medical and pharmacy costs were determined from first diagnosis of UFs until a related procedure or until estimated menopause. Outcomes for patients treated with a procedure (hysterectomy, myomectomy, or embolization), medication, and watchful waiting (no procedure, no UF-related drug) were compared. When determining hysterectomy complication rates for the population of women in the Medicaid database, a total of 1,323 pre- or postmenopausal patients with UFs were included. RESULTS: Overall, 20% of patients were treated with medication, 33% with a procedure, and 47% with watchful waiting. Mean total UF costs were: $11,996 (procedure), $2,703 (medication), and $2,118 (watchful waiting). Mean eligibility months were 8.8, 28.8, and 14.1, respectively. Costs/eligible month were: $1,358 (procedure), $151 (watchful waiting), and $94 (medication). The mean hysterectomy cost was $12,107. CONCLUSION: Treatment for UFs is expensive with a mean cost of $5,504 per study patient. The highest costs are seen in patients receiving procedures, which can lead to complications; 15% in this study. Costs for watchful waiting are similar to costs in patients receiving UF-related drugs. Consideration should be given to using non-surgical therapies for the treatment of UFs before procedures are performed. PMID- 17342499 TI - Chemotherapeutic treatment of a pregnant patient with ovarian dysgerminoma. AB - BACKGROUND: Diagnosis of malignant ovarian tumours during pregnancy is uncommon. This report presents a case of a pregnant woman with ovarian dysgerminoma. CASE REPORT: At 24 weeks gestation, a 33-year-old patient was diagnosed with unilateral ovarian dysgerminoma. Because the tumour was considered to be at an advanced stage (FIGO III), she received three cycles of paclitaxel and carboplatin. At 36 weeks gestation, she underwent a caesarean section, abdominal hysterectomy, bilateral salpingovarectomy, omentectomy, and lymphadenectomy. After surgery, she received three additional cycles of chemotherapy in an adjuvant setting. At birth, the infant was responsive to stimuli, and 20 months after delivery, the infant exhibited normal development. CONCLUSION: This case report illustrates the difficulties arising from diagnosis of malignancy during pregnancy. Although combined treatment with paclitaxel and carboplatin is not considered a first-line therapy for ovarian dysgerminoma, in this case report it elicited an excellent response, and there were no adverse effects on the foetus. PMID- 17342500 TI - Advanced first trimester screening (AFS): an improved test strategy for the individual risk assessment of fetal aneuploidies and malformations. AB - OBJECTIVE: First trimester risk assessment for fetal aneuploidies is computed on the base of a general background risk, which is depending on the maternal age. Thereby, the adjusted risk tends to rise with increasing age. Obversely, more unsuspicious fetal parameters [measurement of the nuchal translucency (NT) and biochemical parameters, free beta human chorionic gonadotropine (fbetaB-Hcg) and pregnancy associated plasma protein A (Papp-A)] have to be observed to result in an unsuspicious test at higher age. It was the aim of this study to investigate the potential value of a novel risk assessment algorithm explicitly disregarding the maternal age. METHODS: This was an ultrasound cohort study of 1,463 singleton pregnancies at 11-14 weeks of gestation undergoing a first trimester screening for fetal aneuploidies by measuring the (NT), Papp-A and fbeta-hCG. In each case, the pregnancy outcome was obtained. Regarding either the detection of genetic affections or the combined detection of genetic or somatic anomalies, the test performance parameters (sensitivity, specificity, positive and negative predictive values) were calculated and compared with each other. For risk calculation the standard Fetal Medicine Foundation (FMF)-Software and an alternative software with a similar algorithm (JOY-Software) were utilized. Compared to this, the risk assessment had been modified by implementing a novel calculation algorithm (advanced first trimester screening algorithm, AFS) purposely disregarding the maternal age and again, the test performance parameters had been computed and were compared with the first ones. RESULTS: At the mere genetic analysis, all four test-strategies revealed to have identical sensitivity and negative predictive values. Compared to the standard FMF Software, the JOY-Software showed a reduced false positive rate. In addition, in both softwares, the false positive rate is highly significant-reduced by implementing the AFS-algorithm. At combined genetic and somatic analysis, analogous results on different counts could be found. CONCLUSION: In the effort to create an algorithm characterising somatic and fetal conditions of the fetus most properly, the inclusion of maternal age is not a helpful value and excluding the age from risk calculation leads to a high significant reduction of the false positive rate. Further, a comparable marked increase of both, specificity and positive predictive values, can be achieved for the FMF- and JOY-Software on the background of the generally more favourable JOY test performance. PMID- 17342501 TI - Inner limiting membrane as membranous support in RPE sheet-transplantation. AB - PURPOSE: To investigate the inner limiting membrane as a scaffold for retinal pigment epithelium cells (RPE). METHODS: Human donor eyes (n = 10) from the Eye Bank Tubingen were used to collect the inner limiting membrane (ILM). These human donor eyes and additional porcine eyes (n = 11) served to isolate RPE cells. A human RPE cell line (ARPE-19) was used as control. RPE cells were cultured on ILM for 3 and 7 days. Phase-contrast photographs of the cells in culture were obtained. Morphology and ultrastructural changes were evaluated by light and transmission electron microscopy. RESULTS: Porcine RPE cells adhere and proliferate when seeded on human ILM. The cells maintained their cuboidal morphology, were polarized, disclosed microvilli on the apical surface, formed intercellular junctions and did not dedifferentiate. Human RPE cells obtained from cadaver eyes barely adhered to the ILM and did not form an intact monolayer. ARPE-19 cells formed a dense colony and maintained epithelial features. CONCLUSION: The ILM is an ideal matrix to establish an intact RPE monolayer and has the potential to be used as sheet for subretinal transplantation. PMID- 17342502 TI - Evaluation of phosphenes elicited by extraocular stimulation in normals and by suprachoroidal-transretinal stimulation in patients with retinitis pigmentosa. AB - BACKGROUND: To determine the efficient parameters to evoke electrical phosphenes is essential for the development of a retinal prosthesis. We studied the efficient parameters in normal subjects and investigated if suprachoroidal transretinal stimulation (STS) is effective in patients with advanced retinitis pigmentosa (RP) using these efficient parameters. METHODS: The amplitude of pupillary reflex (PR) evoked by transcorneal electrical stimulation (TcES) was determined at different frequencies in eight normal subjects. The relationship between localized phosphenes elicited by transscleral electrical stimulation (TsES) and the pulse parameters was also examined in six normal subjects. The phosphenes evoked by STS were examined in two patients with RP with bare light perception. Biphasic pulses (cathodic first, duration: 0.5 or 1.0 ms, frequency: 20 Hz) were applied through selected channel(s). The size and shape of the phosphenes perceived by the patients were recorded. RESULTS: The maximum PR was evoked by TcES with a frequency of 20 Hz. The brightest phosphene was elicited by TsES with a pulse train of more than 10 pulses, duration of 0.5-1.0 ms and a frequency of 20 to 50 Hz. In RP patients, localized phosphenes were elicited with a current of 0.3-0.5 mA (0.5 ms) in patient 1 and 0.4 mA (1.0 ms) in patient 2. Two isolated or dumbbell-shaped phosphenes were perceived when the stimulus was delivered through two adjacent channels. CONCLUSION: Biphasic pulse trains (> or =10 pulses) with a duration of 0.5-1.0 ms and a frequency of 20-50 Hz were efficient for evoking phosphenes by localized extraocular stimulation in normal subjects. With these parameters, STS is a feasible method to use with a retinal prosthesis even in advanced stages of RPs. PMID- 17342503 TI - Elevated vascular endothelial growth factor levels in Coats disease: rapid response to pegaptanib sodium. AB - PURPOSE: The purpose was to report a case of elevated intraocular vascular endothelial growth factor (VEGF) levels in a 2-year-old boy with stage 4 Coats disease. DESIGN: Interventional case report. METHODS: A 2-year-old boy with severe Coats disease and complex retinal detachment refractory to surgical intervention underwent two injections of intravitreal pegaptanib sodium in his right eye 8 weeks apart. RESULTS: After intravitreal injection there was a marked reduction in VEGF (908 to 167 pg/ml) levels and improvement of exudation, hemorrhage, and nearly complete reattachment of his retina within 3 weeks of treatment. The patient remains stable 6 months post-treatment. CONCLUSIONS: Coats disease may have a component of dysregulation of VEGF-mediated angiogenesis as evidenced by elevated levels in this patient. PMID- 17342504 TI - A two-year prospective study comparing lidocaine 2% jelly versus peribulbar anaesthesia for 25G and 23G sutureless vitrectomy. AB - PURPOSE: To evaluate the efficacy of topical lidocaine 2% gel with or without peroral preoperative sedation as an alternative anaesthetic method in sutureless vitreoretinal surgery. MATERIAL-METHOD: A prospective study was designed to assess the intraoperative and postoperative pain, using a visual analogue scale (VAS) in three groups of patients, comprised of 23 patients each. The first group included cases that were operated with 25-gauge (25G) instruments under topical anaesthesia with lidocaine jelly, the second group with 23-gauge (23G) under the same topical anaesthesia and finally the third group (control group) with sutureless (23- or 25-gauge) vitrectomy under peribulbar anaesthesia. Mann Whitney U test was used to compare the results. The subjective surgeon's opinion about the difficulty of each procedure was recorded on a 1-5 scale and the results were evaluated with a chi-square test. RESULTS: No statistically significant difference in the level of pain was detected between the three groups. Topical anaesthesia vitrectomy procedures were performed more easily (p = 0.0002) with 23-gauge than with 25-gauge instruments. The painful steps of the surgery that were capable of causing moderate to severe pain were endolaser, scleral indentation and peribulbar injection. The goal of the operations was accomplished in all cases. CONCLUSION: Lidocaine 2% jelly with or without peroral preoperative morphine and dixyrazine offers adequate analgesia to perform sutureless vitrectomy. Lack of akinesia does not prevent a successful surgical result. PMID- 17342505 TI - Mietz H, Krieglstein GK: Postoperative application of mitomycin C improves the complete success rate of primary trabeculectomy: a prospective, randomized trial. Graefes Arch Clin Exp Ophthalmol 2006; 244: 1429-1436. PMID- 17342507 TI - Testing for association based on excess allele sharing in a sample of related cases and controls. AB - Samples consisting of a mix of unrelated cases and controls, small pedigrees, and much larger pedigrees present a unique challenge for association studies. Few methods are available for efficient analysis of such a broad spectrum of data structures. In this paper we introduce a new matching statistic that is well suited to complex data structures and compare it with frequency-based methods available in the literature. To investigate and compare the power of these methods we simulate datasets based on complex pedigrees. We examine the influence of various levels of linkage disequilibrium (LD) of the disease allele with a marker allele (or equivalently a haplotype). For low frequency marker alleles/haplotypes, frequency-based statistics are more powerful in detecting association. In contrast, for high frequency marker alleles, the matching statistic has greater power. The highest power for frequency-based statistics occurs when the disease allele frequency closely matches the frequency of the linked marker allele. In contrast maximum power of the matching statistic always occurs for intermediate marker allele frequency regardless of the disease allele frequency. Moreover, the matching and frequency-based statistics exhibit little correlation. We conclude that these two approaches can be viewed as complementary in finding possible association between a disease and a marker for many different situations. PMID- 17342508 TI - Use of digital webcam images to track spring green-up in a deciduous broadleaf forest. AB - Understanding relationships between canopy structure and the seasonal dynamics of photosynthetic uptake of CO(2) by forest canopies requires improved knowledge of canopy phenology at eddy covariance flux tower sites. We investigated whether digital webcam images could be used to monitor the trajectory of spring green-up in a deciduous northern hardwood forest. A standard, commercially available webcam was mounted at the top of the eddy covariance tower at the Bartlett AmeriFlux site. Images were collected each day around midday. Red, green, and blue color channel brightness data for a 640 x 100-pixel region-of-interest were extracted from each image. We evaluated the green-up signal extracted from webcam images against changes in the fraction of incident photosynthetically active radiation that is absorbed by the canopy (f (APAR)), a broadband normalized difference vegetation index (NDVI), and the light-saturated rate of canopy photosynthesis (A(max)), inferred from eddy flux measurements. The relative brightness of the green channel (green %) was relatively stable through the winter months. A steady rising trend in green % began around day 120 and continued through day 160, at which point a stable plateau was reached. The relative brightness of the blue channel (blue %) also responded to spring green up, although there was more day-to-day variation in the signal because blue % was more sensitive to changes in the quality (spectral distribution) of incident radiation. Seasonal changes in blue % were most similar to those in f (APAR) and broadband NDVI, whereas changes in green % proceeded more slowly, and were drawn out over a longer period of time. Changes in A(max) lagged green-up by at least a week. We conclude that webcams offer an inexpensive means by which phenological changes in the canopy state can be quantified. A network of cameras could offer a novel opportunity to implement a regional or national phenology monitoring program. PMID- 17342509 TI - Sporulation and diversity of arbuscular mycorrhizal fungi in Brazil Pine in the field and in the greenhouse. AB - The aim of this work was to assess the sporulation and diversity of arbuscular mycorrhizal fungi (AMF) at different forest sites with Araucaria angustifolia (Bert.) O. Ktze. (Brazil Pine). In addition, a greenhouse experiment was carried out to test the use of traditional trap plants (maize + peanut) or A. angustifolia to estimate the diversity of AMF at each site. Soil samples were taken in two State Parks at southwestern Brazil: Campos do Jordao (Parque Estadual de Campos do Jordao [PECJ]) and Apiai (Parque Estadual Turistico do Alto Ribeira [PETAR]), Sao Paulo State, in sites of either native or replanted forest. In PECJ, an extra site of replanted forest that was impacted by accidental fire and is now in a state of recuperation was also sampled. The spore densities and their morphological identification were compiled at each site. In the greenhouse, soil samples from each site were used as inoculum to promote spore multiplication on maize + peanut or A. angustifolia grown on a sandy, low-fertility substrate. Plants were harvested, respectively, after 4 months or 1 year of growth and assessed for mycorrhizal root colonization. Spore counts and identification were also performed in the substrate, after the harvest of plants. Twenty-five taxa were identified considering all sites. Species richness and diversity were greater in native forest areas, being Acaulospora, the genus with the most species. Differences in number of spores, diversity, and richness were found at the different sites of each State Park. Differences were also found when maize + peanut or A. angustifolia were used as trap plants. The traditional methodology using trap plants seems to underestimate the diversity of the AMF. The use of A. angustifolia as trap plant showed similar species richness to the field in PECJ, but the identified species were not necessarily the same. Nevertheless, for PETAR, both A. angustifolia and maize + peanut underestimated the species richness. Because the AMF sporulation can be affected by many conditions, it is impossible to draw detailed conclusions from this kind of survey. More precise experiments have to be set up to isolate the different factors that modulate the ecophysiological interactions between host plant and endophyte. PMID- 17342510 TI - Autograft versus interbody fusion cage without plate fixation in the cervical spine: a randomized clinical study using radiostereometry. AB - A primary object with a fusion cage is avoidance of graft collapse with subsequent subsidence and malalignment of the cervical spine that is observed after bone grafting alone. No randomized studies exist that demonstrate the difference between these two methods in terms of graft subsidence and angulation of the fused segment. The size of the study population was calculated to be 24 patients to reach a significant difference at the 95% CI level. Patients with one level cervical radiculopathy scheduled for surgery were randomized to anterior discectomy and fusion (ACDF) with autograft or to fusion cage, both without plate fixation. Tantalum markers were inserted in the two adjacent vertebrae at the end of surgery. Radiostereometry was performed immediately postoperatively and at regular intervals for 2 years. Questionnaires were used to evaluate the clinical outcome and an unbiased observer graded the outcome after 2 years. No significant differences were found between the two methods after 2 years in regard of narrowing of the disc space (mean 1.7 and 1.4 mm, respectively) or deformation of the fused segment into flexion (mean 7.7 degrees and 4.6 degrees , respectively). Patients in the cage group had a significantly better clinical outcome. The findings of subsidence and flexion deformation of the fused segment after 2 years seem to be of no clinical importance after one-level cervical disc surgery. However, in multi-level surgery using the same methods, an additive effect of the deformations of the fused segments may affect the clinical outcome. PMID- 17342511 TI - Non-genetic expression of adolescent idiopathic scoliosis: a case report and review of the literature. AB - Treating children with idiopathic scoliosis can amaze someone at the many different ways in which the deformity can present. Most authors state that genetics stipulates the course of adolescent idiopathic scoliosis. This is mainly based on the high concordance in monozygotic twins. However, there is indication that environmental factors have influences on adolescent idiopathic scoliosis. This is the first report in which a monozygotic twin pair is described concordant for idiopathic scoliosis but with different apical levels, magnitudes and age at detection of scoliosis which stresses the importance of environmental factors. PMID- 17342512 TI - Letter to the Editor concerning "A hypothesis of chronic back pain: ligament subfailure injuries lead to muscle control dysfunction" (M. Panjabi). PMID- 17342513 TI - Deferred consent in emergency intensive care research: what if the patient dies early? Use the data or not? PMID- 17342514 TI - Should dialysis be offered to cancer patients with acute kidney injury? AB - OBJECTIVES: Cancer patients are at high risk for acute kidney injury (AKI), which is associated with high mortality when renal replacement therapy is required. Because physicians might be reluctant to offer dialysis to patients with malignancies, we sought to appraise outcomes in critically ill cancer patients (mainly with hematological malignancies) who received renal replacement therapy for AKI complicating cancer management. DESIGN: Cohort study including consecutive patients who received renal replacement therapy for AKI complicating cancer management, over a 42-month period. Their mortality was compared with that of non-cancer patients who received renal replacement therapy in the same center over the same study period (control group). SETTING: A 12-bed medical intensive care unit in a university hospital. RESULTS: 94 critically-ill cancer patients met the inclusion criteria. Median SAPS II was 53 (IQR 40-75) and median Logistic Organ Dysfunction score was 7 (IQR 5-10). The etiology of AKI was multiple in most patients (248 identified factors in 93 patients). Hospital mortality was 51.1%. Two variables were independently associated with hospital mortality: the severity of associated organ failures at ICU admission (OR, 1.33; 95% CI, 1.11 1.59; per point) and renal function deterioration after ICU admission (OR, 5.42; 95% CI, 1.62-18.11). Characteristics of the malignancy were not associated with hospital mortality. The presence of cancer had no detectable influence on hospital mortality after adjustment for gender, age, acute severity as assessed by the SAPS II score, and chronic health status [OR 1.2, 95% CI 0.63-2.27; p=0.57]. CONCLUSION: ICU admission should be considered in selected critically ill cancer patients with AKI requiring renal replacement therapy. PMID- 17342515 TI - Population pharmacokinetics and pharmacodynamics of cefpirome in critically ill patients against Gram-negative bacteria. AB - OBJECTIVES: To develop a population pharmacokinetics model for cefpirome in ICU patients, to assess pharmacokinetic-pharmacodynamic profiles vs. MIC distribution of likely ICU pathogens, and to assess their expected cumulative fraction of response (CFR). DESIGN AND SETTING: Prospective observational study in a multidisciplinary ICU. MEASUREMENTS AND RESULTS: Twelve patients received 2g cefpirome intravenously over 12h. Thirteen blood samples were taken on two occasions. Demographic and creatinine clearance data were collected. Based on the final covariate model obtained using NONMEM, Monte Carlo simulations were undertaken to simulate free-drug concentrations for two administration methods: intermittent bolus administration (IBA) and continuous infusion (CI) with a loading dose of 0.5 g. Concentration-time profiles were evaluated by the probability of achieving free-drug concentrations above the MIC for more than 65% of dosing interval. Using MIC distributions from the EUCAST programme the CFR for each method was evaluated. A three-compartment model with zero-order input best described the concentration-time data. The CFR for Escherichia coli and Klebsiella spp. was greater than 97% in all IBA and CI doses but for Pseudomonas aeruginosa, and Acinetobacter spp. achieved target concentrations of 56% and 46%, respectively. High-dose CI cefpirome (6g/day) for P. aeruginosa and Acinetobacter spp. was required to achieve CFR of 89%. CONCLUSION: Measured creatinine clearance appears to be a good marker of cefpirome clearance and potentially could be used to individualise cefpirome therapy. When given as IBA or CI for E. coli and Klebsiella spp., cefpirome should be successful. Cefpirome fails to achieve the bactericidal target even when administered at high-doses such as 6g/day for P. aeruginosa and Acinetobacter spp. Prospective clinical studies are needed to conclusively validate these findings. PMID- 17342516 TI - The thin line between life and death. PMID- 17342517 TI - Emergency feasibility in medical intensive care unit of extracorporeal life support for refractory cardiac arrest. AB - OBJECTIVE: To report the feasibility, complications, and outcomes of emergency extracorporeal life support (ECLS) in refractory cardiac arrests in medical intensive care unit (ICU). DESIGN AND SETTING: Prospective cohort study in the medical ICU in a university hospital in collaboration with the cardiosurgical team of a neighboring hospital. PATIENTS: Seventeen patients (poisonings: 12/17) admitted over a 2-year period for cardiac arrest unresponsive to cardiopulmonary resuscitation (CPR) and advanced cardiac life support, without return of spontaneous circulation. INTERVENTIONS: ECLS femoral implantation under continuous cardiac massage, using a centrifugal pump connected to a hollow-fiber membrane oxygenator. MEASUREMENTS AND RESULTS: Stable ECLS was achieved in 14 of 17 patients. Early complications included massive transfusions (n=8) and the need for surgical revision at the cannulation site for bleeding (n=1). Four patients (24%) survived at medical ICU discharge. Deaths resulted from multiorgan failure (n=8), thoracic bleeding(n=2), severe sepsis (n=2), and brain death (n=1). Massive hemorrhagic pulmonary edema during CPR (n=5) and major capillary leak syndrome (n=6) were observed. Three cardiotoxic-poisoned patients (18%, CPR duration: 30, 100, and 180 min) were alive at 1-year follow-up without sequelae. Two of these patients survived despite elevated plasma lactate concentrations before cannulation (39.0 and 20.0 mmol/l). ECLS was associated with a significantly lower ICU mortality rate than that expected from the Simplified Acute Physiology Score II (91.9%) and lower than the maximum Sequential Organ Failure Assessment score (>90%). CONCLUSIONS: Emergency ECLS is feasible in medical ICU and should be considered as a resuscitative tool for selected patients suffering from refractory cardiac arrest. PMID- 17342518 TI - Undergraduate training in the care of the acutely ill patient: a literature review. AB - OBJECTIVE: To characterise the problem of teaching acute care skills to undergraduates and to look for potential solutions. DESIGN: Systematic literature review including Medline, EMBASE, CINAHL. Eligible studies described education and training issues focusing on caring for acutely ill patients. Articles were excluded if they did not address either educational or clinical aspects of acute care and resuscitation. MEASUREMENT AND RESULTS: We identified and reviewed 374 articles focusing on training or clinical aspects of caring for the acutely ill patient. Undergraduates and junior physicians lack knowledge, confidence and competence in all aspects of acute care, including the basic task of recognition and management of the acutely ill patient. There is wide variability both between and within countries regarding the amount of teaching in critical care offered to undergraduate medical students. Many centres are starting to use an integrated approach to acute care teaching, with early exposure to basic life support and clinical skills, coupled with later exposure to more complex acute care topics. Clinical attachments remain a popular method for training in acute care. Acute care courses are increasingly being used to standardise delivery of practical skills and patient management training. CONCLUSION: The training of healthcare staff in the care of acutely ill patients is suboptimal, adding to patient risk. Improvements in training should start at undergraduate level for maximal effect, should be integrated with postgraduate education, and are likely to enhance current efforts to improve patient safety in acute care. PMID- 17342519 TI - Mechanical complications and malpositions of central venous cannulations by experienced operators. A prospective study of 1794 catheterizations in critically ill patients. AB - OBJECTIVE: Incidence of primary mechanical complications and malpositions associated with landmark-guided central venous access procedures (CVAP) performed by experienced operators. DESIGN: Prospective 5-year observational study on two intensive care units. INTERVENTION: Only CVAPs using Seldinger technique were evaluated. Age, gender, puncture site, number of cannulation attempts, and complications within 24 hours and malpositions were recorded. PATIENTS: 782 CVAPs in females aged 9-92 yrs and 1012 CVAPs in males aged 6-89 yrs. RESULTS: We analyzed 1794 (1017 right- and 777 left-sided CVAP), of which 87.7% were accomplished without adverse events. More than one cannulation attempt was a risk factor for failed catheterization, other mechanical complications but not for malposition. Complications/malpositions were encountered in 220 CVAPs.In 51 CVAPs (2.8%) the cannulation failed at the attempted site, here 18 CVAPs were accompanied by further complications (35.3%). Otherwise, the rate for mechanical complications was low (3.3%). The most common mechanical complications (n = 127) were arterial punctures (n = 52; 2.9%), including four arterial cannulations (0.2%), and pneumothorax (n = 9; 0.6%). There was significant risk for arterial puncture with the internal jugular vein approach in comparison to the innominate vein (p = 0.004), but not to the subclavian vein (p = 0.065). Male patients had a lower risk for failure (2.1%) than females (3.8%, p = 0.028). One-hundred-twenty one central venous catheters were malpositioned (6.7%) of which 35 were related to the left internal jugular vein. CONCLUSIONS: Even experienced operators cause a considerable number of early mechanical complications and malpositions. After two unsuccessful cannulation attempts failure and associated complications are very likely. PMID- 17342520 TI - Hypoxemia due to increased venous admixture: influence of cardiac output on oxygenation. PMID- 17342522 TI - Chondromyxoid fibroma: a rare tumor with an unusual location. AB - Chondromyxoid fibroma constitutes a rare benign tumor of the bones, which has a potential of regional enlargement towards the local tissues. An adult male patient at the age of 28 suffered a fracture of the lateral malleolus due to an eccentric, lytic, lobular lesion in the epiphysis, during a basketball match. The differential diagnosis included the chondroblastoma, the aneurysmal cyst and the chondrosarcoma. After the removal of the tumor with curettage, both with curette and with a high-speed burr, osseous cement was placed in the cavity of the lesion. The biopsy of the tumor confirmed the diagnosis of the chondromyxoid fibroma. This is the first unusual location of the tumor in the national bibliography. The patient after 5 years post-operatively does not show either clinical or radiological signs of regional recurrence of the tumor. PMID- 17342523 TI - A case report of firearm bullet settling into the thoracic spinal canal without causing neurological deficit or vertebral bone destruction. AB - OBJECTIVE: The main objective of this study was to present a case of gunshot injury in which a bullet particle settled into the inferior-thoracic epidural canal, which was neurologically intact, without causing any vertebral bone destruction. There has been no previous report in the literature regarding a foreign body settling into the vertebral canal following gunshot injury without causing any bony destruction. CASE REPORT: A 40-year-old male patient was hospitalized in emergency service with the complaints of severe pain in his back and both legs secondary to a gunshot wound. The entrance wound of the traversing projectile was located at the level of the tenth costa at the inferior of the right scapula. Neurological examination revealed no motor deficit. His lung X-ray was normal at radiological examination. Direct radiograph determined a bullet nucleus on the medium line at thoracolumbar level T-12. Intracanalicular bullet nucleus was found at posterior epidural at the T-12 level on thoracic CT, myelography and CT myelography. No vertebral bone destruction was seen in the direct radiograph studies and serial CT. T12 total laminectomy was performed and epidural foreign body removed. The patient, whose pains ameliorated during the postoperative process, was discharged without any neurological deficit. CONCLUSION: We prefer removal of firearm particles settling into the spinal canal in view of possible later complications such as infection and the toxic effect of the metallic particles, unless there appears any risk of neurological detriment to the patient. PMID- 17342521 TI - Fractures in children with Pompe disease: a potential long-term complication. AB - BACKGROUND: Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Classic infantile-onset disease, characterized by cardiomegaly and profound weakness, leads to death in the first year of life from cardiorespiratory failure. Reversal of cardiomyopathy and improved motor function have been shown in clinical trials of rhGAA enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme), recently approved for clinical use. Increased survival potentially unmasks long-term complications of this previously lethal disease, including risk of skeletal fracture, recently identified at our institution and not previously reported in children with Pompe disease. OBJECTIVE: To report the risk of fracture in children with Pompe disease with increased survival with ERT. MATERIALS AND METHODS: We present four cases of fracture in patients with classic infantile Pompe disease treated with ERT at our institution, and review a study database for additional reports of fracture in this population. RESULTS: We review 19 fractures in 14 children with Pompe disease on ERT. CONCLUSION: Radiologists should be familiar with and vigilant for the association of fractures and increased survival on ERT in children with Pompe disease. We discuss potential mechanisms, implications for radiographic surveillance, potential intervention, and needs for further research. PMID- 17342525 TI - [Lateral tube repositioning following a Baerveldt glaucoma implant. An alternative surgical procedure in the case of repeated conjunctival arrosion]. AB - Conjunctival arrosion of the silicone tube following glaucoma implant surgery is a postoperative complication that generally requires surgical revision by means of a sclera or dura patch with mobilization of adjacent conjunctiva. We present a case of repeated conjunctival arrosion following Baerveldt implant surgery, in which successful revision was achieved over the course of a year by changing the insertion site of the silicone tube into the anterior chamber without touching the plate of the glaucoma implant. However, a long enough silicone tube is absolutely essential if this strategy is to work. PMID- 17342524 TI - Conformational studies of the manganese transport regulator (MntR) from Bacillus subtilis using deuterium exchange mass spectrometry. AB - The manganese transport regulator (MntR) of Bacillus subtilis is a metalloregulatory protein responsible for regulation of genes involved in manganese uptake by this organism. MntR belongs to the iron-responsive DtxR family, but is allosterically regulated by manganese and cadmium ions. Having previously characterized the metal binding affinities of this protein as well as the DNA-binding activation profiles for the relevant metal ions, we have focused the current study on investigating the structural changes of MntR in solution upon binding divalent transition metal ions. Deuterium exchange mass spectrometry was utilized to investigate the deuterium exchange dynamics between apo-MntR, Co(2+)-MntR, Cd(2+)-MntR, and Mn(2+)-MntR. Comparing the rates of deuteration of each metal-bound form of MntR reveals that the N-terminal DNA-binding motif is more mobile in solution than the C-terminal dimerization domain. Furthermore, significant protection from deuterium exchange is observed in the helices that contribute metal-chelating amino acids to form the metal binding site of MntR. In contrast, the bulk of the DNA-binding winged helix-turn-helix motif shows no difference in deuterium exchange upon metal binding. Mapping of the deuteration patterns onto the crystal structures of MntR yields insight into how metal binding affects the protein structure and complements earlier studies on the mechanism of MntR. Metal binding acts to rigidify MntR, thereby limiting the mobility of the protein and reducing the entropic cost of DNA binding. PMID- 17342526 TI - [Urticaria]. PMID- 17342527 TI - [National and international information sources for medical personnel and patients]. AB - The Internet sites listed in this article provide patients and physicians with extensive information on urticaria, mastocytosis and allergies in general. They are user-friendly and enable patients to easily acquire information. PMID- 17342528 TI - [Differential diagnosis of urticaria]. AB - Urticaria is usually a straightforward clinical diagnosis because of the distinctive appearance of both hives and angioedema. Because of differences in clinical manifestations, trigger factors, and duration, 12 different types of urticaria have been identified. The clinical appearance of urticaria may also differ over the course of time; an unquestionable case of urticaria may take on another appearance. Furthermore, there are associated diseases, which have to be taken into consideration for chronic urticaria. PMID- 17342529 TI - Characterization of the dszABC genes of Gordonia amicalis F.5.25.8 and identification of conserved protein and DNA sequences. AB - Gordonia amicalis F.5.25.8 has the unique ability to desulfurize dibenzothiophene and to metabolize carbazole [Santos et al., Appl Microbiol Biotechnol 71:355-362, 2006]. Efforts to amplify the dsz genes from G. amicalis F.5.25.8 based on polymerase chain reaction (PCR) primers designed using the dsz gene sequences of Rhodococcus erythropolis IGTS8 were mostly unsuccessful. A comparison of the protein sequences of dissimilar desulfurization enzymes (DszABC, BdsABC, and TdsABC) revealed multiple conserved regions. PCR primers targeting some of the most highly conserved regions of the desulfurization genes allowed us to amplify dsz genes from G. amicalis F.5.25.8. DNA sequence data that include nearly the entirety of the desulfurization operon as well as the promoter region were obtained. The most closely related dsz genes are those of G. alkinovorans strain 1B at 85% identity. The PCR primers reported here should be useful in microbial ecology studies and the amplification of desulfurization genes from previously uncharacterized microbial cultures. PMID- 17342530 TI - Sparks and embers of skeletal muscle: the exciting events of contractile activation. AB - Intracellular calcium concentration ([Ca(2+)](i)) is a key player in a wide range of cellular functions from long-term effects that determine the fate of the cell to immediate responses as secretion and motility. To initiate contraction, calcium ions in skeletal muscle are released into the myoplasm through the calcium channels, the ryanodine receptors, of the sarcoplasmic reticulum. The opening of these channels give rise to localised increases in [Ca(2+)](i), originally termed calcium sparks, that fuse and generate the global calcium transient. Whereas calcium sparks in amphibians are abundant and stereotyped, events in mammalian skeletal muscle are scarce and morphologically diverse. This review compares the different forms of calcium release events, occurring spontaneously or evoked by a depolarising pulse, observed in the different classes of vertebrates. It then addresses the questions whether or not these events can be considered as elementary and how the global calcium transient can be reconstructed from them. PMID- 17342531 TI - Central fatigue explains sex differences in muscle fatigue and contralateral cross-over effects of maximal contractions. AB - A sustained voluntary contraction increases central fatigue and produces a 'cross over' of fatigue during a subsequent contraction of the contralateral limb. These studies compared the magnitude of these changes for men and women. Force and electromyographic responses from dominant (study 1; n = 8 men, 8 women) or non dominant (study 2; n = 7 men, 8 women) leg extensors to nerve stimulation were recorded at rest and during brief maximal voluntary contractions (MVCs), before and after 100-s sustained MVCs performed with the dominant leg. For the dominant leg, force was reduced more for men (by approximately 24%) than women (by approximately 16%, P < 0.05) after the sustained contractions. Similarly, voluntary activation during these contractions was reduced more for men (by approximately 22%) than women (by approximately 9%, P < 0.05). Conversely, resting twitches changed similarly for both sexes (P > 0.05). For the non dominant leg, men experienced a reduction in force (by approximately 13%, P < 0.001) and had greater deficits in activation than women ( approximately 9% vs approximately 3%, P < 0.05), after sustained contractions of the dominant leg. Therefore, sustained MVCs produce greater central fatigue and a more pronounced 'cross-over' of effects to the contralateral limb for men compared to women. These findings demonstrate distinct differences between sexes in the way the nervous system adapts to changes associated with fatigue. PMID- 17342532 TI - Ketamine blocks voltage-gated K(+) channels and causes membrane depolarization in rat mesenteric artery myocytes. AB - Clinical doses of ketamine typically increase blood pressure, heart rate, and cardiac output. However, the precise mechanism by which ketamine produces these cardiovascular effects remains unclear. The voltage-gated K(+) (K(V)) channel is the major regulator of resting membrane potential (E (m)) and vascular tone in many arteries. Therefore, we sought to evaluate the effects of ketamine on K(V) currents using the standard whole-cell patch clamp recordings in single myocytes, enzymatically dispersed from rat mesenteric arteries. Ketamine [(+/-)-racemic mixture] inhibited K(V) currents reversibly and concentration dependently with a K ( d ) of 566.7 +/- 32.3 microM and Hill coefficient of 0.75 +/- 0.03. The inhibition of K(V) currents by ketamine was voltage independent, and the time courses of channel activation and inactivation were little affected. The effects of ketamine on steady-state activation and inactivation curves were also minimal. Use-dependent inhibition was not observed either. S(+)-ketamine inhibited K(V) currents with similar potency and efficacy as the racemic mixture. The average resting E (m) in rat mesenteric artery myocytes was -44.1 +/- 4.2 mV, and both racemic and S(+)-ketamine induced depolarization of E (m) (15.8 +/- 3.6 and 24.3 +/- 5.0 mV at 100 microM, respectively). We conclude that ketamine induces E (m) depolarization in vascular myocytes by blocking K(V) channels in a state independent manner, which may contribute to the increased vascular tone and blood pressure produced by this drug under a clinical setting. PMID- 17342533 TI - Antigiardial activity of Ocimum basilicum essential oil. AB - In this study, we investigated the effects of Ocimum basilicum essential oil on Giardia lamblia and on the modulation of the interaction of these parasites by peritoneal mouse macrophage. The essential oil (2 mg/ml) and its purified substances demonstrated antigiardial activity. Linalool (300 microg/ml), however, was able to kill 100% parasites after 1 h of incubation, which demonstrates its high antigiardial potential. Pretreatment of peritoneal mouse macrophages with 2 mg/ml essential oil dilution reduced in 79% the association index between these macrophages and G. lamblia, with a concomitant increase by 153% on nitric oxide production by the G. lamblia-ingested macrophages. The protein profiles and proteolitic activity of these parasite trophozoites, previously treated or not with 2 mg/ml essential oil or with the purified fractions, were also determined. After 1 and 2 h of incubation, proteins of lysates and culture supernatants revealed significant differences in bands patterns when compared to controls. Besides, the proteolitic activity, mainly of cysteine proteases, was clearly inhibited by the essential oil (2 mg/ml) and the purified linalool (300 microg/ml). These results suggest that, with G. lamblia, the essential oil from O. basilicum and its purified compounds, specially linalool, have a potent antimicrobial activity. PMID- 17342535 TI - Determination of nitrogen in boron carbide by instrumental photon activation analysis. AB - Boron carbide is widely used as industrial material, because of its extreme hardness, and as a neutron absorber. As part of a round-robin exercise leading to certification of a new reference material (ERM-ED102) which was demanded by the industry we analysed nitrogen in boron carbide by inert gas fusion analysis (GFA) and instrumental photon activation analysis (IPAA) using the 14N(gamma,n)13N nuclear reaction. The latter approach is the only non-destructive method among all the methods applied. By using photons with energy below the threshold of the 12C(gamma,n)11C reaction, we hindered activation of matrix and other impurities. A recently installed beam with a very low lateral activating flux gradient enabled us to homogeneously activate sample masses of approximately 1 g. Taking extra precautions, i.e. self-absorption correction and deconvolution of the complex decay curves, we calculated a nitrogen concentration of 2260+/-100 microg g-1, which is in good agreement with our GFA value of 2303+/-64 microg g-1. The values are the second and third highest of a rather atypical (non-S-shape) distribution of data of 14 round-robin participants. It is of utmost importance for the certification process that our IPAA value is the only one not produced by inert gas fusion analysis and, therefore, the only one which is not affected by a possible incomplete release of nitrogen from high-melting boron carbide. PMID- 17342534 TI - Species assignation amongst morphologically cryptic larval Digenea isolated from New Zealand topshells (Gastropoda: Trochidae). AB - In New Zealand, a single morphotype, comprising three genetically distinct opecoelid species, infects four sympatric species of trochid snails. Two species (a and b) are specific to Diloma subrostrata while the third (c) is more general, capable of infecting three species, most commonly D. aethiops but never D. subrostrata. We sampled three D. subrostrata and D. aethiops populations, in which infection levels ranged from 0 to 29.2%, and attempted species assignation based on host information, restriction fragment length polymorphism (RFLP) analysis and morphology. Host information allowed reliable separation of species a and b from species c. Restriction mapping of ribosomal DNA internal transcriber spacer 2 (ITS2) demonstrated that the restriction enzyme SfuI only digested ITS2 from species b and c. Thus, restriction digests + host species information allowed reliable species assignation. Morphological measurements were taken for both sporocysts and cercariae dissected from 83 infected snails. Substantial overlap existed between measurements for the three species, and discriminant analysis showed that parasites could not be unequivocally assigned to a species- error rates ranged from 9 to 58%--despite statistically significant differences among several means. Amongst this group of digeneans, host information + RFLP provide a rapid, unambiguous method of species assignation that host information + morphological measurements cannot. PMID- 17342536 TI - Thiourea catalysis of MeHg ligand exchange between natural dissolved organic matter and a thiol-functionalized resin: a novel method of matrix removal and MeHg preconcentration for ultratrace Hg speciation analysis in freshwaters. AB - Ultratrace analysis of dissolved MeHg in freshwaters requires both dissociation of MeHg from strong ligands in the sample matrix and preconcentration for detection. Existing solid phase extraction methods generally do not efficiently adsorb MeHg from samples containing high concentrations of natural dissolved organic matter. We demonstrate here that the addition of 10-60 mM thiourea (TU) quantitatively releases MeHg from the dissolved matrix of freshwater samples by forming a more labile complex (MeHgTU+) that quantitatively exchanges MeHg with thiol-functionalized resins at pH approximately 3.5 during column loading. The contents of these columns were efficiently eluted with acidified TU and MeHg was analyzed by Hg-TU complex ion chromatography with cold-vapor atomic fluorescence spectrometry detection. Routinely more than 90% of MeHg was recovered with good precision (average relative standard deviation of 6%) from natural waters obtained from pools and saturated sediments of wetlands and from rivers containing up to 68.7 mg C L-1 dissolved organic matter. With the preconcentration step, the method detection limit of 0.29 pg absolute or 0.007 ng L-1 in 40-mL samples is equivalent to that of the current state-of-the- art as practiced by skilled analysts. MeHg in 20-50-mL samples was completely trapped. On the basis of our knowledge of the chemistry of the process, breakthrough volume should depend on the concentrations of TU and H+. At a TU concentration of 12 mM breakthrough occurred between 50 and 100 mL, but overall adsorption efficiency was still 85% at 100 mL. Formation of artifactual MeHg is minimal; only about 0.7% of ambient MeHg is artifactual as estimated from samples spiked with 4 microg L-1 HgII. PMID- 17342537 TI - An electrochemiluminescent sensor for glucose employing a modified carbon nanotube paste electrode. AB - A carbon nanotube paste (CNTP) electrode and a carbon nanotube paste/glucose oxidase (CNTP/GOx) electrode were prepared, and the electrochemiluminescent (ECL) behavior of luminol in the presence of glucose was investigated in detail at each of these electrodes. Compared to the classical carbon paste (CP) electrode, the CNTP electrode incorporating glucose oxidase greatly enhanced the response of the ECL sensor to glucose due to the electrocatalytic activity of the carbon nanotubes, the specificity of the enzymatic reaction, and the sensitivity of the luminol ECL reaction. Under optimal conditions, the electrode was found to respond linearly to glucose in the concentration range 1.0x10(-6) approximately 2.0x10(-3) mol/L, and the detection limit (defined as the concentration that can be detected at a signal-to-noise ratio of 3) was found to be a glucose concentration of 5.0x10(-7) mol/L. The method used to prepare the CNTP/GOx electrode was very convenient, and the electrode surface could be renewed in the case of fouling by simply polishing or cutting it to expose a new and fully active surface. The relative standard deviations (RSD) were found to be 6.8% and 8.9% for the CNTP electrode and the CNTP/GOx electrode (n=6). The electrode retained 95% of its initial response after two weeks. PMID- 17342538 TI - Teaching analytical atomic spectroscopy advances in an environmental chemistry class using a project-based laboratory approach: investigation of lead and arsenic distributions in a lead arsenate contaminated apple orchard. PMID- 17342539 TI - An accurate QSRR model for the prediction of the GCxGC-TOFMS retention time of polychlorinated biphenyl (PCB) congeners. AB - Quantitative structure-retention relationship (QSRR) models were constructed for the GCxGC-TOFMS retention time of 209 polychlorinated biphenyl (PCB) congeners. Principal component analysis (PCA) was used to recognize groups of samples with similar behavior and assist the separation of the data into training and test sets. The best multi-linear regression (BMLR) method was used for the systematic development of multi-linear regression equations; the best regression model involved four descriptors which were related to GCxGC-TOFMS chromatographic retention of PCBs. The obtained model has good predictive ability. For the test set, it gave a predictive correlation coefficient (R) of 0.988 and an average absolute relative deviation (AARD) of 3.08%. Results of a six-fold cross validation procedure, which were in accordance with those from validation of training and test sets, demonstrated that this model was reliable. Additionally, this paper provides a simple, practical, and effective method for analytical chemists to predict the retention times of PCBs in GC. PMID- 17342540 TI - 10th International Symposium on Biological and Environmental Reference Materials (BERM 10). PMID- 17342541 TI - Harmonized internal quality aspects of a multi-residue method for determination of forty-six semivolatile compounds in water by stir-bar-sorptive extraction thermal desorption gas chromatography-mass spectrometry. AB - Three main aspects of internal quality-internal method validation, internal quality control (IQC), and sample result uncertainty-have been established for a multi-residue method for determination of 46 organic micropollutants (pesticides and polycyclic aromatic hydrocarbons) in water by stir-bar-sorptive extraction (SBSE) and thermal desorption (TD) coupled to capillary gas chromatography-mass spectrometry (GC-MS). From data obtained with increasing time, the process mean and standard deviation were used to harmonize the internal quality statistics. The relationship between these statistics and the hydrophobicity of the compounds was evaluated. PMID- 17342542 TI - A re-appraisal of the reliability of the 20 m multi-stage shuttle run test. AB - Most studies that have set out to quantify the test-retest reliability of the multi-stage shuttle run test (MSSRT) have typically used inappropriate statistics (correlation coefficients) and/or one of two possible calculation methods for deriving predictions of maximal oxygen uptake (VO2max), and have not considered the impact of habituation on performance in the MSSRT and whether its reliability improves beyond a single repeat trial. In this context, the aim of this study was to assess the reliability of the MSSRT over three trials. Thirty-five healthy and active university games players (22 males and 13 females) performed the MSSRT on three occasions, 1 week apart. Individual total numbers of completed shuttles were recorded and estimated VO2max values were derived via established equation and table methods. Analysis revealed that the overall mean VO2max score from the equation method (52.5 +/- 7.8 ml kg(-1) min(-1)) was significantly higher than that for the table (46.9 +/- 8.9 ml kg(-1) min(-1)), whilst the mean trial 2 and trial 3 scores were significantly higher than that for trial 1, but not different to each other. The Limits of Agreement for the table method were -1.4 +/- 5.0 (trial 1-trial 2) and 0.0 +/- 5.5 ml kg(-1) min(-1) (trial 2-trial 3), and for the equation method -1.1 +/- 4.7 (trial 1-trial 2) and 0.0 +/- 5.0 ml kg(-1) min( 1) (trial 2-trial 3). These results suggest that systematic bias is eliminated after the first trial (due to habituation), but a considerable amount of random error remains, regardless of the type of score calculated. Hence, among our sample, the MSSRT does not appear to be reliable enough for the purpose of monitoring changes in VO2max due to non-random reasons. PMID- 17342543 TI - Hemodynamic and neurohumoral responses to the restriction of femoral blood flow by KAATSU in healthy subjects. AB - The application of an orthostatic stress such as lower body negative pressure (LBNP) has been proposed to minimize the effects of weightlessness on the cardiovascular system and subsequently to reduce the cardiovascular deconditioning. The KAATSU training is a novel method to induce muscle strength and hypertrophy with blood pooling in capacitance vessels by restricting venous return. Here, we studied the hemodynamic, autonomic nervous and hormonal responses to the restriction of femoral blood flow by KAATSU in healthy male subjects, using the ultrasonography and impedance cardiography. The pressurization on both thighs induced pooling of blood into the legs with pressure-dependent reduction of femoral arterial blood flow. The application of 200 mmHg KAATSU significantly decreased left ventricular diastolic dimension (LVDd), cardiac output (CO) and diameter of inferior vena cava (IVC). Similarly, 200 mmHg KAATSU also decreased stroke volume (SV), which was almost equal to the value in standing. Heart rate (HR) and total peripheral resistance (TPR) increased in a similar manner to standing with slight change of mean blood pressure (mBP). High-frequency power (HF(RR)) decreased during both 200 mmHg KAATSU and standing, while low-frequency/high-frequency power (LF(RR)/HF(RR)) increased significantly. During KAATSU and standing, the concentration of noradrenaline (NA) and vasopressin (ADH) and plasma renin activity (PRA) increased. These results indicate that KAATSU in supine subjects reproduces the effects of standing on HR, SV, TPR, etc., thus stimulating an orthostatic stimulus. And, KAATSU training appears to be a useful method for potential countermeasure like LBNP against orthostatic intolerance after spaceflight. PMID- 17342544 TI - The validity of estimating quadriceps volume from single MRI cross-sections in young men. AB - Muscle size is often reported as a single anatomical cross-sectional area (ACSA), rather than volume measured with contiguous MRI scans. However, a single ACSA may provide an inadequate estimate of muscle mass. Therefore, we investigated whether quadriceps muscle volume can be adequately estimated from a single ACSA. In 18 adult males we derived regression equations from which estimates of volume were made. These equations were based on the direct assessment of volume using 11 transverse-plane MRI scans along the entire length of the femur (the gold standard). We estimated volume based on single scans at 40, 50 and 60% of femur length (from the distal end). All estimates of quadriceps volumes were highly correlated to the measured volume and demonstrated a low level of error. R (2) = 0.84, 0.93, 0.90 (all P < 0.01), standard error of estimate (SEE) = 26.8 +/- 5.2, 12.5 +/- 5.4 and 9.9 +/- 5.7%, for single scans taken at 40, 50 and 60% of femur length respectively. In comparison, when volume was estimated using multiple MRI scans corresponding to the maximum ACSA of each muscle the estimate was even better [R (2) = 0.95 (P < 0.01) and SEE = 4.5 +/- 2.7%]. Substituting ACSA from a single MRI scan at 60% of femur length into a previously determined regression equation allows for an estimation of muscle volume with a 10% error of estimate. PMID- 17342545 TI - Relationships between pulmonary oxygen uptake kinetics and other measures of aerobic fitness in middle- and long-distance runners. AB - The purpose of this study was to assess the relationships between on- and off transient pulmonary oxygen uptake kinetics and other measures of aerobic fitness in middle-distance (MD) and long-distance (LD) runners. 16 MD and 16 LD runners participated and each completed a series of tests to determine their maximal oxygen uptake (VO2max) gas-exchange threshold (GET), running economy (RE) and the primary time-constant for VO2 at the onset (tau(on)) and offset (tau(off)) of moderate-intensity treadmill exercise. Relationships between measures were established using Pearson product moment correlations (r). The relationships between VO2 kinetic parameter and other aerobic measures varied depending on classification of runner (MD or LD runner). There was a significant relationship between (VO2max) and tau(on) and tau(off) in LD runners (tau(on): r = -0.70, P = 0.003; tau(off): r = -0.55, P = 0.029), but not for MD (tau(on): r = 0.24, P = 0.366; tau(off): r = -0.09, P = 0.739). Similar relationships also existed between GET, RE and kinetic parameters for LD but not MD runners. The inconsistent relationships between VO2 kinetic parameters and other measures of aerobic fitness in MD and LD runners is intriguing. Further work is now required to identify how the volume and intensity of training influence peripheral adaptations in Type I and Type II fibres and how these may, or may not influence VO2 kinetic responses in the moderate- and heavy-intensity domain. PMID- 17342546 TI - [Perioperative cardioprotection. Golden standard beta-blockade?]. AB - Myocardial ischemia is a major cause of perioperative morbidity and mortality. Because of a growing expectancy of lives, the prevalence of cardiovascular diseases is increasing, and thus the number of surgical patients presenting with a cardiovascular risk profile. Based upon pathophysiological considerations, different interventions to lower perioperative cardiovascular risk have been evaluated. The mostly discussed intervention believed to prevent cardiovascular complications in the perioperative period is the use of beta-blockers. Although many authors agree that perioperative beta-blockade is effective in high-risk patients, less is known about the optimal timing, dosage and the identification of patients in whom the intervention would be beneficial. Based upon the available data we try to answer questions about timing and dosage, and we discuss possible side effects and economic questions. Another cardioprotective option is the use of statins. Besides their lipid-lowering properties, so called pleiotropic effects are believed to decrease cardiac risk. Furthermore, different interventions can be used in addition to or as an alternative to perioperative beta-blocker therapy, such as alpha-2 agonists, thoracic epidural analgesia or coronary revascularization. PMID- 17342547 TI - Description of light ion production cross sections and fluxes on the Mars surface using the QMSFRG model. AB - The atmosphere of Mars significantly attenuates the heavy ion component of the primary galactic cosmic rays (GCR), however, increases the fluence of secondary light ions (neutrons, and hydrogen and helium isotopes) because of particle production processes. We describe results of the quantum multiple scattering fragmentation (QMSFRG) model for the production of light nuclei through the distinct mechanisms of nuclear abrasion and ablation, coalescence, and cluster knockout. The QMSFRG model is shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections. We use the QMSFRG model and the space radiation transport code, HZETRN to make predictions of the light particle environment on the Martian surface at solar minimum and near maximum. The radiation assessment detector (RAD) experiment will be launched in 2009 as part of the Mars Science Laboratory (MSL). We make predictions of the expected results for time dependent count-rates to be observed by the RAD experiment. Finally, we consider sensitivity assessments of the impact of the Martian atmospheric composition on particle fluxes at the surface. PMID- 17342548 TI - A case of primary extracranial meningioma of the forearm with bone invasion. AB - We report here a rare case of primary extracranial meningioma in a 73-year-old woman with an asymptomatic mass located in the left distal-dorsal forearm. MRI revealed the lesion to be poorly circumscribed and unclear, with iso-signal intensity to muscle on T1 and with a relatively high signal intensity on T2 weighted imaging. The histopathology of the specimen from incision biopsy was typical of meningioma, showing bland spindle cell proliferation with a whorling pattern. Immunohistochemically, the tumor cells were positive for epithelial membrane antigen and vimentin, and negative for S-100 expression. PMID- 17342549 TI - The eligibility of MIVA approach in thyroid surgery. AB - INTRODUCTION: Thyroid size, by preoperative ultrasound evaluation, is a very important criterion of minimally invasive video-assisted thyroidectomy (MIVAT) exclusion because the working space provided by the technique is limited. The aim of this work is to verify the suitability of MIVAT and its applicability in clinical practice in patients with a thyroid volume up to 50 ml. METHODS: From January 2003 to February 2006, 33 patients were selected for MIVAT. A completely gas-less procedure was carried out through a central skin incision performed "high" between the cricoid and jugular notch. RESULTS: The skin incision performed was from 20 to 35 mm (mean 24.88 mm +/- 2.74) for different thyroid sizes. We obtained in all cases excellent results about patients cure rate and comfort, few cases of postoperative pain, and attractive cosmetic results. CONCLUSION: In this study, we demonstrated that the MIVAT, for thyroids up to 50 ml in volume, is feasible and safe. This procedure allows more patients, who would have been excluded before, to take advantage of this minimally invasive approach with good cosmetic results, highly regarded by young female patients, and reduced paresthetic consequences. PMID- 17342550 TI - Patellofemoral contact pressure following high tibial osteotomy: a cadaveric study. AB - Patella infera is a known complication of high tibial osteotomy (HTO) that can cause anterior knee pain due to excessive stresses associated with abnormal patellofemoral (PF) joint biomechanics. However, the translation of these abnormal biomechanics to native cartilage pressure has not been explored. The present study was designed to compare the PF contact pressures of three different HTOs in a human cadaveric model of valgus tibiofemoral correction. Nine fresh cadaveric knees underwent (1) medial opening wedge (OWHTO) with a proximal tuberosity osteotomy (PTO), (2) OWHTO with a distal tuberosity osteotomy (DTO), and (3) a lateral closing wedge (CWHTO). The specimens were mounted in a custom knee simulation rig, with muscle forces being simulated using a pulley system and weights. The PF contact pressure was recorded using an electronic pressure sensor at 15 degrees , 30 degrees , 60 degrees , 90 degrees , and 120 degrees of knee flexion, with results of the intact knees obtained as relative control. Compared to the intact knee, the DTO OWHTO and CWHTO did not significantly (P > 0.05) influence PF pressure at any flexion angle. On the other hand, PTO OWHTO lead to a significant elevation in PF cartilage pressure at 30 degrees (P < 0.05), 60 degrees (P < 0.005), and 90 degrees (P < 0.0005) knee flexion. We conclude from these results that DTO OWHTO maintains normal joint biomechanics and has no significant effect on PF cartilage pressure. In patients who complain of pre existing anterior knee pain, DTO OWHTO or CWHTO should be considered. PMID- 17342551 TI - Experimental evaluation of early and long-term effects of microparticle embolization in two different mini-pig models. Part II: liver. AB - PURPOSE: To evaluate trisacryl-gelatin microspheres (40-120 microm) for acute and chronic tissue embolization in mini-pig livers. METHODS: Thirteen animals were divided into four groups: group 1 (n = 3), total arterial bed occlusion with acute procedure; groups 2 to 4, chronic superselective embolization with follow up of 1 week (group 2, n = 1), 4 weeks (group 3, n = 4) or 14 weeks (group 4, n = 5). Key endpoints were homogeneity and particle distribution in acute embolizations (group 1) and necrosis and inflammation in chronic embolizations (groups 2-4) as assessed microscopically and angiographically. RESULTS: After liver embolization, parenchymal necrosis did not occur; only signs of vessel wall disintegration were evident. The bile ducts remained intact. A distinct foreign body reaction with sparse leukocytic infiltration and giant cells was found at 14 weeks, but no signs of major inflammation were found. Particles were seen at the presinusoidal level, but no particle transportation into the sinusoids was observed. CONCLUSIONS: Embolization in mini-pig livers, using small trisacryl gelatin microspheres, results in vessel fibrosis without parenchymal or bile duct necrosis. The most likely explanation for preservation of the parenchyma is portal inflow. Small trisacryl-gelatin microspheres may be ideal as an adjunct for chemoembolization. PMID- 17342552 TI - Assessment of compliance performance of environmental regulations of industries in Tuzla (Istanbul, Turkey). AB - Although environmental management in Turkey is evolving, its performance needs to be assessed in terms of the extent to which polluters and dischargers are complying with their legal obligations. In spite of this necessity, however, not a single study evaluating the effectiveness of command-and-control strategy of environmental management has been conducted. It is for this reason that it was decided to conduct an analysis of the impact of environmental legislation on a major industrial area in Turkey. Accordingly, Turkish environmental legislation was analyzed, and all relevant obligations and responsibilities of industry are identified. Based upon this appraisal, a questionnaire was prepared and used to conduct interviews in Tuzla, Istanbul. From the results, it can be concluded that environmental compliance performance of industry is low. The total of 92 parameters has been questioned. Fifty-three parameters have been found as satisfactory compliance, whereas 26 parameters have been classified as partial compliance and 13 as unsatisfactory compliance. The most important reason for inadequate performance is the lack of an effective national and local environmental compliance management system. The other leading reasons are found to be low-level environmental consciousness of the people, absence of environmental management system at the sites, inadequacies in environmental subsidies, and insufficiencies in public environmental infrastructure. Four recommendations are made to increase the effectiveness of compliance management: establishing an effective environmental compliance management system, accelerating public investment for environmental infrastructure, developing financial subsidies and incentive schemes for environmental investments, and encouraging voluntary initiatives. PMID- 17342553 TI - Quantitative structure-activity relationships for predicting the joint toxicity of substituted anilines and phenols to algae. PMID- 17342554 TI - Establishment, characterization, and virus susceptibility of a new marine cell line from red spotted grouper (Epinephelus akaara). AB - A marine fish cell line from the snout of red spotted grouper Epinephelus akaara, a protogynous hermaphrodite, was established, characterized, and subcultured with more than 60 passages. The grouper snout cell line (GSC) cells multiplied well in Dulbecco's modified Eagle's medium (DMEM) medium supplemented with 10% fetal bovine serum. The optimal growth temperature was 25 degrees C, and morphologically the cells were fibroblastic. Chromosome analysis revealed that the GSC cell line has a normal diploid karyotype with 2n = 8st + 40t. A virus titration study indicated that the cells were susceptible to turbot Scophthalmus Maximus rhabdovirus (SMRV) (10(8.5) TCID(50) ml(-1)), while the viral titer of frog Rana grylio virus 9807 (RGV(9807)) reached 10(3.5) TCID(50) ml(-1). The infection was confirmed by cytopathic effect (CPE), immunofluorescence, and electron microscopy experiments, which detected the viral particles in the cytoplasm of virus-infected cells, respectively. Further, significant fluorescent signals were observed when the GSC cells were transfected with pEGFP vector DNA, indicating their potential utility for transgenic and genetic manipulation studies. PMID- 17342555 TI - 3D bicipital groove shape analysis and relationship to tendopathy. AB - The bicipital groove of the proximal humerus is formed by the medial and lateral tuberosities and serves to retain the long biceps tendon in its proper place as the arm moves. Bicipital root and proximal tendon disorders are an important symptom generator in the shoulder. The accuracy of the diagnosis of many shoulder disorders visually without quantitative shape analysis is limited, motivating a clinical need for some ancillary method to assess the proximal biceps. In previous studies, measurements of bicipital groove shape were 2-dimensional (2D), taken from a single axial slice. Because of significant variations in groove shape from one axial slice to another in a single patient, such approaches risk overlooking shape features important to long biceps tendon pathology. In this paper, we present a study of the relationship between bicipital groove shape and long biceps tendon pathology using a novel 3-dimensional (3D) shape descriptor for the bicipital groove. In addition to providing quantitative measures of the shape of the groove and its relation to tendopathy, the new descriptor allows for intuitive, descriptive visualization of the shape of the groove. PMID- 17342556 TI - Randomized trial of health-related quality of life after open and laparoscopic surgery for colon cancer. AB - BACKGROUND: Randomized controlled trials (RCTs) have reported improved or unchanged three-year survival following laparoscopic colon resection (LCR) for colon cancer compared with that following open resection (OCR). The aim of this study was to determine health-related quality of life (HRQL) in patients randomized to laparoscopic or open resection for colon cancer. METHODS: In total, 285 patients (130 LCR, 155 OCR) from seven Swedish centers were included. HRQL was assessed preoperatively and at 2, 4, and 12 weeks postoperatively with the EQ 5D and EORTC QLQ-C30 instruments. RESULTS: The LCR patients did significantly better on the social function component of the EORTC QLQ-C30 at two and four weeks and on the role function component at two weeks. CONCLUSION: Laparoscopic resection for colon cancer improved quality of life during the first postoperative month. PMID- 17342557 TI - The preferred choice for radial endosonographic staging of esophageal cancer: standard echoendoscope or nonoptic esophagoprobe? AB - BACKGROUND: The nonoptic esophagoprobe has been reported to be comparable to the standard echoendoscope in esophageal cancer staging, with a superior advantage of traversing more stenotic tumors because of its smaller diameter. The aim of this study was to see whether its use in a general population of esophageal cancer patients confers any significant clinical benefit. METHODS: Five hundred seventy seven consecutive patients referred for initial locoregional staging of esophageal cancer were analyzed retrospectively. Comparisons were made between the standard echoendoscope and the esophagoprobe. RESULTS: Complete staging (95.2% vs 77.5%; p < 0.001) was significantly higher in the esophagoprobe group compared with that of the standard echoendoscope group (315 and 262 patients, respectively). In 146 patients with histopathologic verification without prior chemotherapy or radiotherapy, the esophagoprobe was comparable in T-staging accuracy to the standard echoendoscope in those with traversable tumors (89.2% vs. 82.8%; p = 0.213). However, the presence of a nontraversable stricture significantly decreased standard echoendoscope T-staging accuracy compared with a traversable stricture (33.3% vs. 82.8%, respectively; p < 0.001). The esophagoprobe also picked more advanced tumors and distal nodes. CONCLUSIONS: The esophagoprobe is more accurate than the standard echoendoscope in the T staging of esophageal cancer because of its higher likelihood of traversing tumor stenosis. It can potentially reduce the necessity for dilation in stenotic tumors by four to five times. We propose using the esophagoprobe as the first choice for radial endoscopic ultrasound staging of esophageal cancer. PMID- 17342558 TI - Effect of intercostals neural blockade with Marcaine (bupivacaine) on postoperative pain after laparoscopic cholecystectomy. AB - BACKGROUND: Postoperative pain experienced by patients who undergo laparoscopic cholecystectomy may aggravate surgical complications, prevent early discharge, and cause readmission. This study aimed to evaluate the effectiveness of an intraoperative intercostals neural blockade for the control of postoperative pain after laparoscopic cholecystectomy. METHODS: In a prospective, double-blinded, clinical trial, 61 patients classified as American Society of Anesthesiology (ASA) 1 and 2 undergoing laparoscopic cholecystectomy were randomized to receive only general anesthesia (control group, n = 30) or general anesthesia plus intraoperative intercostals neural blockade using 0.5% bupivacaine-adrenaline at the right side (intercostals group, n = 31). Postoperative pain was assessed according to a pain severity score using a subjective analog visual scale (VAS) 6, 12, and 24 h after the surgery. Systemic narcotic injection was available to all surgically treated patients postoperatively according to their demand. The history, pain severity score, and all postoperative data were recorded for each patient. RESULTS: The pain severity score was significantly higher in control group than in the intercostals group (p < 0.001), suggesting that patients who received intercostals neural blockade had less pain postoperatively than the control group. CONCLUSION: Intercostals neural blockade may safely be used to reduce the postoperative pain after laparoscopic cholecystectomy. PMID- 17342559 TI - A two-center experience with the exclusive use of laparoscopic transperitoneal nephrectomy for benign renal disease in children. AB - BACKGROUND: This study aimed to evaluate a two-center experience with pediatric transperitoneal laparoscopic nephrectomy, specifically focusing on the outcome parameters of operative time, complication, analgesic requirement, and postoperative stay. METHODS: This ambispective study was conducted over a 4-year period between May 2001 and May 2005 in two tertiary pediatric surgical centers. Data were prospectively recorded from an in-house expanded medical audit system (EMAS) and a Microsoft Excel database. Information on patient demographics, operative time, complications, analgesic requirement, and length of hospital stay were retrieved and analyzed. RESULTS: A total of 30 consecutive patients with a mean age of 4.43 years (range, 3 months to 15 years) underwent laparoscopic nephrectomy. All the patients underwent unilateral nephrectomy/nephroureterectomy for multidysplastic kidney (n = 12), reflux nephropathy (n = 13), pelvicoureteric junction obstruction (n = 4), or cystic disease of indeterminate cause (n = 1). The mean operative time was 93 +/- 30 min. The principal hemostatic devices used were the Harmonic Scalpel (20 cases), liga clips (5 cases), and hook diathermy and endoshears exclusively (4 cases). There were no conversions, but the intraoperative complications of bleeding (n = 2), difficult location (n = 1), difficult extraction (n = 1), and requirement for a liver retractor (n = 2) were encountered. An additional five patients had problems in the immediate postoperative period, two of whom went on to have long term difficulties with recurrent urinary tract infections resulting from a residual ureteric stump, which required surgery. Nearly one-third of the patients required morphine for analgesia in the immediate postoperative period, with the figure falling to 20% by day 1. The median postoperative hospital stay was 1 day (range, 0-16 days). At this writing, all the patients remain under surveillance with a mean follow-up period of 2.88 years, and no patients have experienced complications secondary to intraabdominal adhesions. CONCLUSION: Transperitoneal laparoscopic nephrectomy is technically feasible in most cases of benign renal disease. The intraoperative complications are minimal, and recovery for most is robust. Two-thirds of the patients are discharged within 24 h. In this study, narcotic analgesics were prescribed in about a one-third of all the cases for a limited period. Further problems may be seen when refluxing ureters are incompletely excised. However, the transperitoneal approach does not mitigate against complete excision because the exposure to the pelvis is adequate. At the midterm follow-up assessment, adhesive obstruction was not encountered, confirming this approach as a tenable alternative to other laparoscopic approaches for nephrectomy. PMID- 17342560 TI - Laparoscopic segmental colorectal resection for endometriosis: limits and complications. AB - BACKGROUND: Deep pelvic endometriosis with colorectal involvement is a complex disorder often requiring segmental bowel resection. This study investigated the limits and complications of laparoscopic segmental colorectal resection. METHODS: Laparoscopic segmental colorectal resection was performed for 71 women with bowel endometriosis. Intra- and postoperative complications were evaluated, together with symptom outcomes, by means of questionnaires completed before and after surgery. Surgical procedures and complications were compared between the first part of the study (40 cases, previously published) and the second part (31 cases). RESULTS: Of the 71 women, 64 (90%) underwent laparoscopic segmental colorectal resection, with 7 requiring laparoconversion. Major complications occurred in nine cases (12.6%), six with rectovaginal fistulae and three with pelvic abscesses. The mean operating time decreased significantly during the study (p < 0.05). The mean follow-up period after colorectal resection was 24.4 +/- 2.2 months. No differences in the rates of laparoconversion or complications were observed between the two periods, whereas major associated surgical procedures were more frequent during the second period. Dysmenorrhea (p < 0.0001), dyspareunia (p = 0.0001), pain at defecation (p = 0.0004), bowel movement pain or cramping (p < 0.0001), lower back pain (p < 0.0001), and asthenia (p < 0.0001) were improved after the operation, with no difference between the study periods. CONCLUSION: This large series confirms the feasibility and efficacy of laparoscopic segmental colorectal resection. However, women must be informed of the risk for potentially severe complications. PMID- 17342561 TI - Adverse effects of porcine small intestine submucosa implants in experimental ventral hernia repair. PMID- 17342562 TI - The clinical significance of bile duct sludge: is it different from bile duct stones? AB - BACKGROUND: Some patients with suspected common bile duct (CBD) stones are found to have sludge and no stones. Although sludge in the gallbladder is a precursor of gallbladder stones, the significance of bile duct sludge (BDS) is poorly defined. This study aimed to compare BDS with bile duct stones in terms of frequency, associated risk factors, and clinical outcome after endoscopic therapy. METHODS: The study enrolled 228 patients who underwent therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for suspected choledocholithiasis. The patients were divided into two groups: patients with BDS but no stones on ERCP and patients with CBD stones. The presence of risk factors for bile duct stones (age, periampullary diverticulum, ductal dilation or angulation, previous open cholecystectomy) were assessed at ERCP. Follow-up data (36 +/- 19 months) were obtained from medical records and by patient questioning. RESULTS: Bile duct sludge occurred in 14% (31/228) of patients and was more common in females. After endoscopic clearance, CBD stones recurred in 17% (33/197) of the patients with CBD stones, and in 16% (5/31) of the patients with BDS (p = 0.99). Common bile duct dilation was less common in the sludge group. The other known risk factors for recurrent CBD stones (age, previous open cholecystectomy, bile duct angulation, and the presence of a peripampullary diverticulum) were not statistically different between the two groups. CONCLUSIONS: The findings indicate that the clinical significance of symptomatic BDS is similar to that of CBD stones. Bile duct sludge seems to be an early stage of choledocholithiasis. PMID- 17342563 TI - How to avoid intraoperative evaluation of sentinel lymph nodes in breast cancer. PMID- 17342564 TI - Selection of patients with colorectal peritoneal carcinomatosis for cytoreductive surgery and perioperative intraperitoneal chemotherapy. AB - BACKGROUND: Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been suggested as a treatment option for patients with colorectal peritoneal carcinomatosis. However, the survival benefit is achieved at the expense of moderate to high perioperative morbidity and mortality. METHODS: This review summarized the important prognostic factors for survival; outlined the patient selection process from major peritonectomy centers, paying particular attention to preoperative evaluation; and identified areas for potential improvement. Emphasis was placed on a strict patient selection process to avoid futile aggressive treatments. RESULTS: Currently, contrast-enhanced computed tomography, magnetic resonance imaging, positron emission tomography, and laparoscopy have been utilized in the preoperative evaluation process to identify potential surgical candidates. Patients with good performance status, low volume of peritoneal disease, and absence of extra-abdominal metastases are more likely to benefit from the combined treatment. CONCLUSIONS: Quantitative assessment of the extent of disease is possible and should be performed at the time of primary cancer operation. Careful selection of patients to identify surgical candidates with favorable prognostic indicators is important. PMID- 17342565 TI - Lymphedema therapy reduces the volume of edema and pain in patients with breast cancer. AB - BACKGROUND: Despite recent advances in breast-conserving surgery, upper-extremity lymphedema remains a problem for patients after the treatment of breast cancer. This study examines the results of a protocol of therapy for lymphedema in breast cancer patients. METHODS: A total of 135 patients with lymphedema after breast cancer treatment were provided a protocol of complete decongestive therapy (CDT). This involved manual lymphatic drainage, compression garments, skin care, and range-of-motion exercises. Therapy was divided into an induction phase involving twice-weekly therapy for 8 weeks and maintenance therapy individualized to patient needs. Absolute volume and percentage of volume of lymphedema was compared before and after treatment. Also assessed was the degree of chronic pain and the need for pain medication. RESULTS: Mean initial lymphedema volume was 709 mL, and the percentage of lymphedema was 31%. The induction phase of CDT reduced this to 473 mL and 18%, respectively. Before therapy, 76 patients had chronic pain and 41 required oral pain medication. CDT reduced this to 20 and 11, respectively. The degree of pain was also assessed on a numerical scale from 0 to 10. Those patients with chronic pain initially rated their pain at an average of 6.9. After treatment, this was reduced to 1.1. CONCLUSIONS: Lymphedema continues to be a problem for patients with breast cancer. A program of lymphedema therapy can reduce the volume of edema and reduce pain in this population. PMID- 17342566 TI - The pylorus: take it or leave it? Systematic review and meta-analysis of pylorus preserving versus standard whipple pancreaticoduodenectomy for pancreatic or periampullary cancer. AB - BACKGROUND: Our objective was to determine the relative effects of pylorus preserving pancreaticoduodenectomy (PPPD) and standard Whipple pancreaticoduodenectomy (SWPD) in patients with pancreatic or periampullary cancer. METHODS: We searched seven bibliographic databases, conference proceedings, and reference lists of articles and textbooks, and we contacted experts in the field of hepatobiliary surgery. We included published and unpublished randomized controlled trials. We evaluated the methodological quality of trials and, in duplicate, extracted data regarding operative, perioperative, and long-term outcomes. We contacted all authors and asked them to provide additional information regarding the trials. We pooled results from the studies by using a random-effects model, evaluated the degree of heterogeneity, and explored potential explanations for heterogeneity. RESULTS: Six trials that included a total of 574 patients met eligibility criteria. In the pooled analysis, PPPD was 72 minutes faster (P < .001, 95% confidence interval [95% CI], 53-92), with 284 mL less blood loss (P < .001, 95% CI, 176-391) and .66 fewer units of blood transfused (P = .002, 95% CI, .25-1.16). Other perioperative and long-term outcomes did not statistically differ, although the confidence intervals include important differences. CONCLUSIONS: Moderate-quality evidence suggests PPPD is a faster procedure with less blood loss compared with SWPD. Large absolute differences in other key outcomes are unlikely; excluding relatively small differences will, however, require larger, methodologically stronger trials. PMID- 17342567 TI - Teaching palliative care and end-of-life issues: a core curriculum for surgical residents. AB - BACKGROUND: Most surgical training programs have no curriculum to teach palliative care. Programs designed for nonsurgical specialties often do not meet the unique needs of surgeons. With 80-hour workweek limitations on in-hospital teaching, new methods are needed to efficiently teach surgical residents about these problems. METHODS: A pilot curriculum in palliative surgical care designed for residents was presented in three 1-hour sessions. Sessions included group discussion, role-playing exercises, and instruction in advanced clinical decision making. Residents completed pretest, posttest, and 3-month follow-up surveys designed to measure the program's success. RESULTS: Forty-seven general surgery residents from Brown University participated. Most residents (94%) had "discussed palliative care with a patient or patient's family" in the past. Initially, 57% of residents felt "comfortable speaking to patients and patients' families about end-of-life issues," whereas at posttest and at 3-month intervals, 80% and 84%, respectively, felt comfortable (P < .01). Few residents at pretest (9%) thought that they had "received adequate training in palliation during residency," but at posttest and at 3-month follow-up, 86% and 84% of residents agreed with this statement (P < .01). All residents believed that "managing end-of-life issues is a valuable skill for surgeons." Ninety-two percent of residents at 3-month follow up "had been able to use the information learned in clinical practice." CONCLUSIONS: With a reasonable time commitment, surgical residents are capable of learning about palliative and end-of-life care. Surgical residents think that understanding palliative care is a useful part of their training, a sentiment that is still evident 3 months later. PMID- 17342568 TI - Regional lymph node metastases; a singular manifestation of the process of clinical metastases in cancer: contemporary animal research and clinical reports suggest unifying concepts. AB - Research results from laboratory animals and human clinical reports provide insight into cancer cell disseminations and elaborate the complex metastatic cascade of cells into both regional lymph nodes and other distant organs. Critical appraisal of clinical trials indicates that lymph node metastases are themselves non-lethal, but indicate prognosis, confirming laboratory conclusions. Distant vital organ metastases can be resected with long term survival in highly selective situations, demonstrating metastatic specificity in oligometastatic disease. Appreciating lymphatic system embryology, anatomy, and physiology is necessary for understanding lymph node metastases. The primary lymphatic system function was to return interstitial fluid to the circulation. Later evolutionary insertion of lymphocyte collections in lymph nodes interrupting lymph flow completed a system of analyzing external antigens to enable adaptive immunologic responses. Human cancers seldom elicit major immunological responses; they are not generally "foreign" enough. Therefore, lymphatic metastases have little meaning in evolutionary terms. Organ specificity of both lymphatic and distant metastases occurs as metastatic cells lie dormant, but grow selectively only in liver, lung, bone, or lymph nodes. These organ specific metastatic cells have little ability to produce different organ site clinical metastases. Thus, laboratory findings and clinical correlations emphasize that surgical lymph node removal should be de-emphasized or omitted. More physiological approaches to the highly manipulable multi-step processes of clinical metastases arising from host microenvironments will eventually prevail. PMID- 17342569 TI - Impact of induction chemotherapy and preoperative chemoradiotherapy on operative morbidity and mortality in patients with locoregional adenocarcinoma of the stomach or gastroesophageal junction. AB - BACKGROUND: Significant tumor downstaging has been achieved in patients with localized gastric or gastroesophageal adenocarcinoma by induction chemotherapy and preoperative chemoradiotherapy (CTX-CTXRT). However, the influence of CTX CTXRT on operative morbidity and mortality has not yet been clarified. The aim of the present study was to document the frequency and nature of morbidity and mortality after surgery combined with CTX-CTXRT, and identify factors predictive of postoperative complications in patients with localized gastric or gastroesophageal adenocarcinoma. METHODS: A prospectively collected database on 71 consecutive patients who underwent CTX-CTXRT at M.D. Anderson Cancer Center between January 1997 and August 2004 was reviewed. Postoperative morbidity and mortality were investigated, and risk factors for overall complications were identified by multivariate logistic regression analysis. RESULTS: Overall morbidity and mortality rates were 38.0% (27 patients) and 2.8% (2 patients), respectively. Age greater than 60 years [relative risk 11.3 (95% confidence interval 2.50-50.6)] and body mass index (BMI) of 26 kg/m(2) or above [relative risk 4.08 (95% confidence interval 1.08 to 15.4)] were significant risk factors for overall complications. CONCLUSIONS: CTX-CTXRT can be performed safely with an acceptable operative morbidity and a low operative mortality rate in patients with gastric or gastroesophageal cancer, with careful consideration of added risk associated with age and obesity. PMID- 17342570 TI - Morphometric parameters of the radial head: an anatomical study. AB - INTRODUCTION: Exact anatomical description of the proximal radius is imperative for the development of radial head prostheses. The purpose of this study was to measure the anatomical parameters of the radial head. METHODS: Optosil imprints of 18 pairs of proximal radii fixed with formalin were taken. All possessed their native cartilage joint surface free of any arthritic defects. After being cut into 3 mm slices, the diameter of each slice was measured in steps of 30 degrees of rotation with the margo interosseous acting as a reference point. RESULTS: Maximum radial head diameter was seen from the 0 to the 9 mm slice at a rotation of 30 degrees to full supination perpendicular to the proximal radioulnar joint. The diameter increased from the radiocapitular joint surface to the 6 mm slice, and then it decreased (P < 0.001). At the level of 6 mm the maximum radial head diameter was 24.13 mm (range 21.2-27.3 mm). The minimum diameter was seen perpendicular to the maximum; it also increased from the radiocapitular joint surface to the 6 mm slice and then decreased. There was a significant difference between the minimum and maximum diameter of each slice at a P-level of P < 0.001. Left and right sides were not significantly different at a P-level of 0.01. CONCLUSION: Our data show that the radial head is neither round nor conical. It has a complex shape with an increasing size from the radiocapitular joint surface to the middle of the proximal radioulnar joint surface. No statistically significant differences could be observed between right and left radii. PMID- 17342571 TI - The lateral atlantooccipital ligament. AB - INTRODUCTION: Stability of the atlantooccipital joint is of vital importance. The ligaments of this region, for the most part, have been thoroughly investigated, except for the lateral atlantooccipital ligament (LAO), which is not described in most modern texts. MATERIALS AND METHODS: The authors examined 20 adult cadaveric specimens to observe the morphology of the LAO. RESULTS: All specimens were found to have an LAO, bilaterally, immediately posterior to the rectus capitis lateralis muscle with a fiber direction more or less opposite to this muscle. The LAO was found in intimate contact with the vertebral artery posteriorly and with the contents of the jugular foramen anteriorly. In all specimens, the origin of this ligament was from the anterolateral aspect of the transverse process of the atlas and the insertion onto the jugular process of the occipital bone. The fibers of the LAO had a mean angle of 26 degrees from the midline. The mean length and width of this ligament was 2.2 and 0.5 cm, respectively. The mean thickness of the LAO was 2 mm. The average tensile strength of this band was 37.5 degrees N. The LAO remained lax with flexion and extension of the craniocervical junction. With contralateral lateral flexion of the craniocervical junction, the LAO became fully taut at a mean of 8 degrees . Partial, but never complete, tautness was observed with rotation of the occipital on the atlas bilaterally. Following sectioning of the LAO, approximately an additional 3 degrees -5 degrees of contralateral lateral flexion was observed. CONCLUSIONS: The LAO is a constant anatomical structure of the craniocervical junction that might be of concern to the clinician. This ligament inhibits lateral flexion of the atlantooccipital joint and its disruption appears to add to instability at this articulation. PMID- 17342572 TI - [Focus: 125 years after the discovery of the tubercle bacillus by Robert Koch - new problems in the worldwide fight against tuberculosis]. PMID- 17342573 TI - [Pulmonary rehabilitation is up and going]. PMID- 17342574 TI - [Teaching the inhalation manoeuvre to asthmatic children by means of visual feedback]. AB - BACKGROUND: For inhalation as a mainstay of asthma therapy, the correct inhalation technique is of utmost importance. This comprises not only the correct handling of the device but also specific device-dependent requirements concerning the inhalation manoeuvre itself. METHODS: We examined whether totally different inhalation manoeuvres can be educated in parallel in asthmatic children. As target manoeuvres we defined: 1) an inhalation as fast as possible (peak inspiratory flow >or= 60 l/min) with high acceleration in the starting phase as it is normally required for dry powder inhalers. 2) A constant inhalation at a flow between 40 and 90 l/min with a long duration as it is regarded to be optimal for propellant driven systems. As models for dry powder inhalers the Diskus (Accuhaler, a medium resistance device) and the Turbuhaler (high resistance) were chosen. As an example of a propellant-driven we used the Autohaler (breath actuated MDI). A total of 52 outpatients (age 4 to 14 years) with asthma were educated two times. We measured peak inspiratory flow (PIF), duration of inspiration with inspiratory flow >or= 30 l/min (Ti30), inspiratory volume (Vol) and acceleration of inspiratory flow (mPIF) through the devices in random order before and after each training session. Measurements were performed using the inhalation manager, a computer based spirometry system, which allows recording of inspiratory manoeuvres through Placebo inhalers by means of a pneumotachometer. Results are immediately visualized (optical feedback) and evaluated. RESULTS: Training children simultaneously with different inhalation systems appeared to be difficult. Only for the DPIs a significant increase of children inhaling in the pre-given target area could be reached. With Diskus, the rate of correct manoeuvres increased from initially 57.7 % to 88.5 % after training and with Turbohaler from 32.7 % to 65.4 %, respectively. With MDI, this rate increased only from 32.7 % to 42.3 %. This indicates that a high inspiratory flow may be easier to be learned than a constant slow inhalation, at least when training is done simultaneously in children. CONCLUSIONS: Thus, training of the different inhalation manoeuvres for DPI and MDI should be performed separately. When prescribing inhaled drugs for reliever treatment and maintenance therapy for any individual patient, prescribers should select inhalation devices, which can be used in a similar way without clinical disadvantage. PMID- 17342575 TI - [False-positive interferon-gamma test?]. AB - M. tuberculosis specific interferon-gamma tests have been established lately as an important additional instrument in the diagnosis of the latent tuberculosis infection (LTBI). In several studies these tests had a higher specificity compared to the tuberculin skin test (TST). In this report we describe the case of a woman without increased risk for LTBI and with discordant results for the interferon-gamma tests QuantiFERON-TB Gold In-Tube and T-SPOT.TB and for the TST. The findings suggest repeated false-positive results of the QuantiFERON-TB Gold In-Tube test. PMID- 17342576 TI - [Occupational allergies to bromelain]. AB - The protease bromelain originating from the pineapple fruit (Ananas comosus) finds frequent use in industry. Exposure to enzyme dusts has long been known to cause occupational allergies. The present paper reviews the results of the evaluation of literature data concerning occupational airway sensitization due to bromelain. Cases of specific airway sensitization caused by bromelain could be shown clearly by the presented studies. Since the symptoms, results of skin prick tests, detection of specific IgE antibodies and results of specific bronchoprovocation tests are consistent, an immunological mechanism can be assumed. PMID- 17342577 TI - [Lung cancer: targeted therapy]. AB - An increased understanding of the biology of lung cancer has identified biological targets for rationally designed novel therapies. Most of these targets are components of signalling pathways or metabolic processes. EGFR-tyrosinkinase inhibitors have become standard in second- and thirdline therapy of NSCLC, the anti-VEGF-antibody Avastin combined with first-line chemotherapy showed a significant survival benefit over chemotherapy alone. There are ongoing studies with targeted therapies in all stages of lung cancer. Major advances of these new drugs are their low toxicity and, in part, the oral application. PMID- 17342578 TI - [Obituary for Robert Koch]. PMID- 17342579 TI - [Nocardiosis as a differential diagnosis of a PET-positive pulmonary nodule]. AB - We describe the case of a 76-year-old immunocompetent man suspected to have lung cancer in the right upper lobe on the basis of radiographic and clinical findings. The tumour could not be confirmed histologically by transbronchial biopsy. In the fluorodeoxyglucose positron emission tomography (FDG-PET) we found a significantly elevated standard uptake value (SUV) of 13.4. The patient underwent thoracotomy with excision of the tumour, the histological diagnosis was chronic pneumonia. Tissue culture revealed Nocardia spp. Using 16-rDNA-gene sequence analysis the species was identified as Nocardia abscessus. The patient was treated with trimethoprim-sulfamethoxazol regarding the susceptibility profile and improved remarkably both clinically and radiographically. PMID- 17342580 TI - [Diagnosis and treatment of acute pulmonary embolism]. PMID- 17342582 TI - Negative chronotropic and atrioventricular blocking effects of taxine on isolated frog heart and its acute toxicity in mice. AB - The alkaloid mixture of yew ( TAXUS BACCATA) was converted to sulphate salt and this salt form of the drug was used throughout the experiments. The median lethal doses (LD50) and their 19/20 confidence limits of two samples of the drug, the freshly prepared and the stored taxine sulphate, were determined on mice (s. c.) and found as 12.96 (11.37-14.77) and 13.09 (11.73-14.61) mg/kg, respectively. There was no significant difference between these values. Results show that taxine in salt form can be preserved for long periods without loosing its properties. The cardiac actions of the drug (10-100 microg/ml) were determined on isolated frog heart. It was found that the drug slows both atrial and ventricular rate dose-dependently, however, the rate-depressing effect was more prominent on the ventricle, e.g., in the highest concentration, the observed percent changes in cardiac rate (mean +/- S.E.M.) were 38.29 +/- 4.13 for atrium and 1.71 +/- 0.80 for ventricle, indicating that the atrioventricular conduction is more susceptible to the drug. The effect of the drug on the heart could be removed partially by washing. At the end of this procedure, the atrial and ventricular rates reached 56.63 +/- 5.44 and 51.35 +/- 5.54 that of control rates, respectively. From these findings and those observed by previous authors, it is deduced that the actions of taxine on heart might result from its Ca (2+) antagonizing properties, but electrophysiological studies are necessary for a definitive conclusion. PMID- 17342581 TI - [Measuring airway inflammation in clinical practise - application and interpretation]. AB - Airway inflammation plays a major role in the pathology of both asthma and COPD and is the target of corticosteroid treatment. In daily routine practise, however, airway inflammation is still not often considered by pneumologists to support the diagnostic process or to aid in disease management, despite studies showing that patients could benefit. Eosinophilic airway inflammation is of special interest, as it is not restricted to allergen-induced airway diseases, and because it generally responds well to anti-inflammatory treatment with corticosteroids. Therefore, the early detection of this kind of underlying inflammatory process can have a positive impact on finding a diagnosis as well as for disease management. The non-invasive detection of eosinophilic airway inflammation using induced sputum is too time consuming and therefore too expensive in outpatient settings. As sputum eosinophils correlate with the concentration of exhaled nitric oxide (FeNO), its measurement could serve as a more economic alternative, especially as new small handheld analysers are available now, that allow the rapid FeNO analysis, even in children. This review will cover some basics and technical aspects of FeNO measurements, which should be known to correctly interprete results in clinical practise. In the second part, the clinical value and the limits of FeNO measurements, as well as the potential interpretation of results are discussed based on recently published literature. PMID- 17342583 TI - Anti-Anaphylactic Properties of Thonningia sanguinea. AB - The anti-anaphylactic properties of extracts of THONNINGIA SANGUINEA, a plant used prophylactically against asthma were investigated using experimental anaphylaxis in the guinea pig. The results show that when administered orally, aqueous extract of the plant material inhibited anaphylactic contractions in isolated ileal pieces, reduced the sensitivity of ileal pieces to exogenous histamine, reduced the amount of histamine and mepyramine-resistant spasmogens released anaphylactically from lung tissues, and reduced the total histamine content of the lung. These properties could be responsible for the prophylactic action of the plant preparation. PMID- 17342584 TI - Separation and quantitation of protoanemonin in ranunculaceae by normal- and reversed-phase HPLC. AB - A method is described for the extraction and high-performance liquid chromatographic separation and quantitation of the lactone protoanemonin in leaves of Ranunculaceae. For samples with a protoanemonin concentration over 10 microg/g W. W., a reversed-phase technique using a Lichrosorb RP 18 column and a binary solvent system was developed. Alternatively, for samples with a lower lactone concentration, a normal-phase technique with a Lichrosorb Si 60 and quaternary elution system was elaborated. Protoanemonin was detected at 258 nm; its calibration curves were established, and its response factor was calculated using, as standard, the pure compound extracted from HELLEBORUS NIGER. A survey of ten different taxa of Ranunculaceae was performed and it showed the suitability of the method for routine work with high sensitivity limit. PMID- 17342585 TI - Investigations of Medicinal Plants of Euphorbiaceae and Thymelaeaceae Occurring and Used in Thailand; II. Cryptic Irritants of the Diterpene Ester Type from Three Excoecaria species1. AB - From leaves of E. OPPOSITIFOLIA the irritant EXCOECARIA factor O (1) was isolated. Its structure 1 was shown to be identical with that of a factor obtained by transesterification of the cryptic EXCOECARIA factor group O (')(z) from the latex of the plant. From the non-irritant ethyl acetate fractions of the latices of E. AGALLOCHA, E. OPPOSITIFOLIA and E. BICOLOR, three TLC-homogenous non-irritant mixtures A (')(z), O (')(z) and B (')(z) were isolated and shown to represent non-separable cryptic EXCOECARIA factor groups containing 9,13,14 orthoesters of 5beta-hydroxyresiniferonol esterified in 20-position. The mixtures may be activated by mild treatment with sodium methoxide to generate mixtures of highly irritant factor groups A (z), O (z) and B (z) together with mixtures of aliphatic acid methylesters. The former may be separated partially by reversed phase TLC and yielded EXCOECARIA factors O (1), O (2), A (3), B (3) and B (4) together with residual non-separable factor groups. The structures 1-5 of the individual daphnane type irritant EXCOECARIA factors were elucidated by spectroscopic means. Their irritant activities were determined quantitatively on the mouse ear. The mixtures of methyl esters of aliphatic acids were analyzed by GC. Thus the complete structures of the cryptic factor groups from latex were deduced. PMID- 17342586 TI - The Influence of Boron Deficiency on Glandular Scale Development and Structure in Mentha piperita. AB - The influence of boron deficiency on glandular scale development in MENTHA PIPERITA was studied under controlled experimental conditions in solution culture. Young leaves of peppermint were examined by light and electron microscope. The differentiation stages of glands from the initial gland cell up to a 10-cell glandular scale were the same in both control and boron-deficient plants. Boron had no influence on the numer of cells in glandular scale development. During gland development a number of ultrastructural alterations occured. The most striking and earliest ultrastructural response to boron deficiency was thickness and irregularity of cell walls. The ultrastructural changes observed in young glands are believed to be senescing phenomena, which normally appear at the postsecretory stage. The acceleration of cell aging during boron deficiency restricts essential oil secretion to a short period. PMID- 17342587 TI - New Vernolepin Derivatives from Vernonia glabra and Glaucolides from Vernonia scorpioides. AB - The aerial parts of VERNONIA GLABRA afforded in addition to vernolepin, vernodalin and vernomenin, four further sesquiterpene lactones derived from vernolepin ( 1), two germacranolides and together with vernodalol the corresponding lactone 9. From VERNONIA SCORPIOIDES two further glaucolides ( 14) and ( 15) were isolated. The structure of the tiglate ( 16) is revised. The structure were elucidated by spectroscopic methods. PMID- 17342588 TI - Stimulation der Immunantwort durch Inhaltsstoffe aus Baptisia tinctoria. AB - Contents of BAPTISIA TINCTORIA have been evaluated for their immunostimulating capability. Aqueous-ethanolic extracts had a low toxicity in regard to interference with the DNS-metabolism. Fractions of these extracts, which had been purified by column chromatography, exhibited a significant potential for lymphoblastoid transformation. It could also be shown that the production of antibodies against sheep red blood cells was enhanced by polysaccharide fractions from BAPTISIA TINCTORIA. PMID- 17342589 TI - Occurrence of psilocybin in various higher fungi from several European countries. AB - Using high performance liquid and thin-layer chromatographic methods more than 100 species of fungi from Europe belonging to 18 genera were analysed for the hallucinogenic compound psilocybin and for some related tryptamine derivatives. Psilocybin, psilocin and/or baeocystin were found in 3 PSILOCYBE 1 PANAEOLUS, 5 INOCYBES and one PLUTEUS. PSILOCYBE SEMILANCEATA and PANAEOLUS SUBBALTEATUS proved to be the only psilocybin-containing fungi that can be gathered in Middle and Northern Europe in sufficient quantities to permit abuse. PMID- 17342590 TI - Studies on the Turnover of Cardenolides in Convallaria majalis. AB - In leaves of CONVALLARIA MAJALIS L. the cardenolide content is known to decrease towards the end of the vegetation period. However, at this stage the rate of biosynthesis is even higher than at the onset of flowering. This has been revealed by photosynthesis experiments in the presence of (14)CO (2) and the subsequent isolation of 15 labelled cardenolides using PC, TLC and HPLC. IN VITRO and IN VIVO experiments showed that the first step in the degradative pathway of convalloside is deglucosidation yielding convallatoxin, followed by conversion into several yet unidentified degradation products other than known cardenolides of C. MAJALIS. This indicates that the cardenolides of C. MAJALIS are subjected to a turnover at least towards the end of the vegetation period. PMID- 17342591 TI - Iridoid Glucoside of Swertia japonica. AB - The structure of senburiside I, a new iridoid glucoside isolated from SWERTIA JAPONICA, was elucidated to be 7-epi-( M-hydroxybenzoyl)-2'-sinapoyl-loganic acid. PMID- 17342592 TI - Plants as Sources of Antimalarial Drugs Part. 1. In vitro Test Method for the Evaluation of Crude Extracts from Plants. AB - An IN VITRO antimalarial test, utilising the inhibition of uptake of [G- (3)H] hypoxanthine into PLASMODIUM FALCIPARUM cultured in human blood, has been used to assess the activity of crude extracts of ARTEMISIA ANNUA and A. VULGARIS (Compositae) and of BRUCEA JAVANICA, AILANTHUS ALTISSIMA, and SIMABA CEDRON (Simaroubaceae). PMID- 17342593 TI - Sesquiterpenlactone aus Arnica chamissonis IV.1,2 Ivalin und andere Sesquiterpenlactone aus den Blutenkorbchen der Subspecies genuina. AB - The flowers of ARNICA CHAMISSONIS ssp. GENUINA afforded in addition to 8 helenanolides ivalin, the first eudesmanolide found in the genus ARNICA. PMID- 17342594 TI - Effects of Saikosaponins on Liver Tyrosine Aminotransferase Activity induced by Cortisone in Adrenalectomized Rats. AB - Liver tyrosine aminotransferase activity is known to be induced by administration of steroids to adrenalectomized rats. When saikosaponin a, b (1), b (2), b (3), b (4), c, d or f was injected intraperitoneally into adrenalectomized rats, no induction of liver tyrosine aminotransferase activity was observed. Administration of a low dose of cortisone (6.4 micromol/kg) to adrenalectomized rats also did not induce liver tyrosine aminotransferase. But this enzyme was induced on administration of this low dose of cortisone with saikosaponen a (6.4 or 12.8 micromol/kg), d (6.4 or 12.8 micromol/kg) or f (12.8 micromol/kg). The sturcture-activity relationship of the effects of various Saikosaponins on the action of cortisone is discuused. PMID- 17342595 TI - Inhaltsstoffe und Pharmakologie der Okoubaka aubrevillei-Rinde. AB - From the stembark of OKOUBAKA AUBREVILLEI (+)-catechin, (-)-epicatechin, (+) gallocatechin, (-)-epicatechingallate, (-)-epigallocatechingallate, gallic and protocatechuic acid have been isolated. The antimicrobial and immunostimulating activity of the drug extract were assigned to the phenolic compounds. PMID- 17342596 TI - Coumarin Derivatives from Eryngium campestre1. AB - Aegelinol benzoate, a new dihydroxanthyletin ester and the known coumarin esters agasyllin and grandivittin, as well as, aegelinol have been isolated from ERYNGIUM CAMPESTRE roots using column chromatography and subsequent semipreparative HPLC. The structures of the compounds have been elucidated by a combination of spectroscopic methods. PMID- 17342597 TI - Iridoids from Verbascum species. AB - The occurrence of iridoids from 16 VERBASCUM species was investigated. The negative ion mass spectroscopy of the acetylated compounds was very useful concerning the appearance of a molecular ion. The fragmentation behaviour of the iridoids under positive and negative ionization is compared and discussed. PMID- 17342598 TI - Constituents of Essential Oil of Elsholtzia strobilifera1. AB - The composition of the essential oil of ELSHOLTZIA STROBILIFERA, growing around Naini Tal (India) has been investigated by capillary gas-chromatography, gas chromatography-mass spectrometry and (13)C-NMR spectroscopy. Out of about 50 identified mono- and sesquiterpenoids, pinocarvone is the most abundant component, which has not been identified in any species of ELSHOLTZIA before. The acylfuran derivatives reported from other species of ELSHOLTZIA could not be detected. PMID- 17342599 TI - Flavonoids from Inula viscosa. AB - Phytochemical study of the aerial parts of INULA VISCOSA resulted in the isolation of sixteen flavonoids. One of them, 3- O-acetylpadmatin [(2 R,3 R)-3 acetoxy-5,3',4'-trihydroxy-7-methoxyflavanone], was isolated for the first time as a natural compound. Ferulic aldehyde, 2-methylphloroacetophenone, inuviscolide and 2-deacetoxyxanthinin were also isolated. PMID- 17342600 TI - Die Alkaloide von Uncaria tomentosa und ihre Phagozytose-steigernde Wirkung. AB - From the roots of UNCARIA TOMENTOSA six oxindol alkaloids have been isolated and identified as isopteropodin, pteropodin, mitraphyllin, isomitraphyllin, rynchophyllin and isorynchophyllin. By ion pair chromatography on HPLC a fingerprint analysis has been worked out which allowed to differentiate between various UNICARIA-species and drug preparations. With the exception of mitraphyllin and rynchophyllin all alkaloids showed a pronounced enhancement effect on phagozytosis, determined in two IN VITRO tests and the IN VIVO-carbon clearance test. PMID- 17342601 TI - Hypotensive action of 3alpha-dihydrocadambine, an indole alkaloid glycoside of uncaria hooks1. AB - 3alpha-Dihydrocadambine exhibited dose-dependent hypotensive and anti hypertensive effects in anesthetized normotensive rats and in conscious spontaneously hypertensive rats. Its activity was much stronger and longer lasting than that of rhynchophylline. In anesthetized dogs, it caused dilation of the vertebral, femoral and common carotid arteries, and had almost no effect on the coronary artery, whereas it had almost no significant activity in isolated canine arterial strip preparations. PMID- 17342602 TI - Uber 5 neue Umbelliferonether aus Galbanumharz1. AB - From Galbanum beside genuin umbelliferon five umbelliferon ethers are isolated and identified as 7-{[1 R-(1alpha,2beta,4abeta,6alpha,8aalpha)] -2,6-Dihydroxy 2,5,5,8a-tetramethyldecahydronaphthalen-1-ylmethoxy} -2 H-1-benzopyran-2-one, 1, 7-{[1 R-(1alpha,4abeta,8aalpha)]-6-Hydroxy-2,5,5,8a-tetramethyl-1,4,4a,5,6,7,8,8a octahydronaphthalen-4-on-1-ylmethoxy} - 2 H-1-benzopyran-2-one, 2,7-{[1R (1alpha,4abeta,6beta,8aalpha)]-6-Hydroxy-2,5,5,8a -tetramethyl-1,4,4a,5,6,7,8,8a octahydronaphthalen-1-ylmethoxy} - 2 H-1-benzopyran-2-one, 3, 7-{[1R (1alpha,4aalpha,8aalpha)]-6-Hydroxy-2,5,5,8a -tetramethyl-1,4,4a,5,6,7,8,8a octahydronaphthalen-1-ylmethoxy} -2 H-1-benzopyran-2-one, 4, 7-{[1R (1a,4abeta,8abeta)]-2,5,5,8a-Tetramethyl-1,4,4a,5,6,7,8,8a-octahydronaphthalen-4 on-1-ylmethoxy}-2 H-1-benzopyran-2-one, 5. PMID- 17342603 TI - Comparison of chemical and botanical studies of Turkish papaver belonging to the section pilosa. AB - The alkaloidal contents of the Turkish PAPAVER belonging to the section PILOSA have been studied by high performance liquid chromatography. According to the results obtained, the section PILOSA should be divided into two subsections; the first being characterised by the presence of the alkaloids amurine, glaucine and roemerine and the second by protopine and rhoeadine. These conclusions were confirmed by the botanical studies. PMID- 17342604 TI - Hydrogenation of iridoid glucosides with exocyclic double bond. AB - Catalytic hydrogenation of two iridoids of unusual type with an exocyclic double bond, namely serrulatoloside and gardoside methyl ester, over PtO (2) catalyst to give 10-desoxypatrinoside and 8-epiloganin, respectively, is described. PMID- 17342605 TI - Antibiotics from Algae XXXVII. Rhodomelol and Methylrhodomelol from Polysiphonia lanosa1. AB - From the red alga POLYSIPHONIA LANOSA (L.) Tandy two new bromophenols, methylrhodomelol and rhodomelol were isolaed, and after acetylation and methylation their structure elucidated with the aid of spectroscopic methods and an X-ray crystallographic study. PMID- 17342606 TI - Artemisitene, a New Sesquiterpene Lactone Endoperoxide from Artemisia annua. AB - Artemisitene, an endoperoxide closely related to the known antimalarial sesquiterpene artemisinin, has been isolated from ARTEMISIA ANNUA, and its structure has been determined. PMID- 17342607 TI - Structures of crassicauline B and crassicaulidine. AB - Two minor alkaloids, crassicauline B and crassicaulidine, were isolated from the roots of ACONITUM CRASSICAULE (1, 2). The structure of crassicauline B, C (27)H (31)O (4)N, is now deduced as ( 1), while the previously assigned structure of crassicaulidine has been further confirmed as ( 7) on the basis of chemical data and (13)C-NMR spectrum. PMID- 17342608 TI - Reductive electrochemical HPLC assay for artemisinin (qinghaosu). AB - Artemisinin ( QINGHAOSU), a sesquiterpene lactone containing a peroxide bridge, is the known antimalarial constituent of the herb ARTEMISIA ANNUA L. An electrochemical HPLC detection procedure has been developed that provides a sensitive, selective, and rapid assay for artemisinin in crude plant extracts. PMID- 17342609 TI - Isolation and 13C-NMR Studies on Cathovaline, an Alkaloid from the Leaves of Catharanthus roseus. AB - Studies on the alkaloidal constituents of the leaves of CATHARANTHUS ROSEUS have resulted in the isolation of cathovaline. (13)C-NMR studies have been carried out on the alkaloid using ADEPT and APT pulse sequences. Cathovaline has not been previously reported from this plant but has been isolated from the roots of CATHARANTHUS LANCEUS (Boj. ex. A. De) pich (1) and CATHARANTHUS OVALIS Markgraf, sp. nov. (2). PMID- 17342610 TI - Thalivarmine and Thalsivasine: Two New Bisbenzylisoquinoline Alkaloids from Thalictrum minus var. minus. AB - Thalivarmine and thalsivasine, together with the known bases thalmelatidine, thalicberine, O-methylthalicberine, thaliphylline, thalmethine, O methylthalmethine and (-)- N-methylcanadine have been isolated from the above ground parts of THALICTRUM MINUS var. MINUS L. PMID- 17342611 TI - Synthesis of (+/-)-ariensin. AB - Ariensin, a lignan occurring in the exudate of the bark of BURSERA ARIENSIS has been synthesized by a short stereospecific pathway. Dihydrocubebin which occurs in CLEISTANTHUS COLLINUS and PIPER GUINEENSE was also obtained as an intermediate in the reaction sequence. PMID- 17342612 TI - Highly Methylated 6-Hydroxyflavones and Other Flavonoids from Thymus piperella. AB - From the aerial parts of THYMUS PIPERELLA, the free flavone aglycones 5,6 dihydroxy-7,8,4'-trimethoxyflavone ( 1), 5,6-dihydroxy-7,8,3',4' tetramethoxyflavone ( 2), 5,6-dihydroxy-7,3',4'-trimethoxyflavone ( 3), ladanein ( 4) (5,6-dihydroxy-7,4'-dimethoxy-flavone), 5-hydroxy-7,4'-dimethoxyflavone ( 5) and apigenin ( 6), the flavanones naringenin ( 7) and eriodictyol ( 8), and the flavone glycosides vicenin-2 ( 9), apigenin-7- O-beta- D-glucoside (10) and luteolin-7- O-beta- D-glucoside ( 11), have been isolated and identified. This is the first time that 5,6-dihydroxy-7,8,4'-trimethoxyflavone has been found as a natural product. PMID- 17342613 TI - Effect of Hypolaetin-8-Glucoside on Human Platelet Aggregation induced by ADP. AB - Hypolaetin-8-glucoside, a flavonoid isolated from SIDERITIS MUGRONENSIS possessing anti-inflammatory activity inhibited dose-dependently the human PRP aggregation induced by ADP with a IC (50) = 2.4 x 10 (-4) M. This action does not seem to be related to cyclo-oxygenase, as this flavonoid is not an inhibitor and even is able to act as a cofactor for this enzyme. PMID- 17342614 TI - Volatile Constituents of Artemisia nilagirica. AB - The essential oil of ARTEMISIA NILAGIRICA was analysed by capillary gas chromatography, IR, (1)H-NMR, and GC-MS. The main constituents of the oil are camphor, beta-eudesmol, 1,8-cineole, borneol, artemisia alcohol, camphene, alpha gurjunene, P-cymene, terpinene-4-ol and alpha-pinene. PMID- 17342615 TI - Further Flavonoids from Orthosiphon spicatus. PMID- 17342616 TI - Antiviral Properties of Garlic: In vitro Effects on Influenza B, Herpes Simplex and Coxsackie Viruses. PMID- 17342617 TI - Caulogenesis in Rhizome Callus of Costus speciosus1. PMID- 17342618 TI - The Cytotoxic Principle of Scutellariae Radix against L1210 Cell. PMID- 17342619 TI - Isolation of Coronaridine from the Seeds of Tabernaemontana penduliflora. PMID- 17342620 TI - Isolation and Identification of (-)-Olivil and (+)-Cycloolivil from Stereospermum kunthianum. PMID- 17342621 TI - New Sesquiterpene Lactones from Centaurea phrygia. PMID- 17342622 TI - Chemical Constituents of the Leaves of Flueggea microcarpa. PMID- 17342623 TI - Phenolic Constituents of Rhus semialata Leaves. PMID- 17342624 TI - Phyllanthol from Phyllanthus sellowianus (Euphorbiaceae). PMID- 17342626 TI - Influence of fruit size of solanum wrightii on its solasodine content. PMID- 17342625 TI - Alkaloids from the Seeds of Corydalis stricta. PMID- 17342627 TI - A New Eudesmane Acid from Dittrichia (Inula) viscosa. PMID- 17342628 TI - Biosynthesis of Radiolabeled Pyrrolizidine Alkaloids from Senecio jacobaea and Senecio vulgaris. PMID- 17342630 TI - [Integration of simulated patients into the study of human medicine in Germany]. AB - BACKGROUND AND OBJECTIVE: Simulated patients (SPs) internationally teach and assess medical students. SPs are healthy lay people who portray the role of a patient, including symptoms and personality. In Germany the first SP programs were introduced in between 1998 and 2000. This study describes the implementation of SP programs at German medical schools. METHODS: In 2004 we used two separate questionnaires to collect data on the existence, time of implementation and planning of an SP program, number of SPs used, organisational structure, teaching and assessment with SPs, timing of the use of SPs within the curriculum, feedback during teaching sessions and quality management tools for such SP programs. RESULTS: 30 out of 36 medical schools were included in the study (83%). The majority of medical schools used SPs for training in communication skills and also for the assessment of competence. Because of the newness of SP programs in Germany, compared with such programs in Anglo-American countries, SP programs have only rarely been used in Germany in postgraduate training and continuing medical education. Compared to other countries German medical schools have spent few resources on the professional training of SPs and rarely use SP trainers to run these-programs. CONCLUSION: For quality assurance medical schools have to support SP-programs adequately. SP trainers should be introduced into German SP programs to release medical doctors from SP training and organisational tasks. Networking, as carried out internationally, should be introduced to foster collaborative research and effectively use limited resources. PMID- 17342631 TI - [Early warning system for pulmonary fluid status monitoring in terminal heart failure]. AB - HISTORY AND ADMISSION FINDINGS: A 38-year-old man was admitted for increasing dyspnea, nausea and emesis during the preceding year. Clinically he was in heart failure NYHA stage III. He had not been on any regular medication and had no other medical complaints. Physical examination revealed a pulse of 100/min., hypotension (100/60 mmHg) and jugular vein distension. Bilateral pulmonary rales were noted on auscultation. A slight edema of both lower legs was noted. INVESTIGATIONS: A 12-lead electrocardiogram showed complete left bundle branch block with a QRS duration of 160 ms. Chest x-ray revealed cardiomegaly with pulmonary vascular congestion. Transthoracic echocardiography demonstrated reduced left ventricular function with an ejection fraction of 10-15%. Left heart catheterization excluded coronary heart disease and confirmed the decreased left ventricular function. TREATMENT AND COURSE: Medical treatment for heart failure secondary to dilated cardiomyopathy was initiated without significant improvement in clinical status. Cardiac resynchronization therapy (CRT) was therefore performed with implantation of a biventricular pacer with defibrillator (CRT-D) and a fluid status monitoring system (OptiVol). Subsequently the patient was able to increase his physical activity to NYHA class II and was followed in our outpatient clinic. Since initial treatment the patient has been seen twice for clinical signs of pulmonary edema. Both times the fluid monitoring system of the CRT-D gave an alarm signal early enough to allow cardiac re-compensation by expanding the current medication. Both times hospital admission was avoided. CONCLUSIONS: Cardiac resynchronization therapy has been established as an adjunct to optimal pharmacological therapy in eligible patients with severe heart failure. A fluid status monitoring system integrated into the device measures intrathoracic impedance, allowing patients to be alerted before the onset of symptoms of fluid overload. Thus, treatment can be adjusted and hospitalization is avoidable. PMID- 17342632 TI - ["Usual" cannabis abuse producing an unusual incident]. AB - CASE HISTORY: A 17-year-old male presented in an agitated, deranged state with rapidly increasing swelling of the neck. Except for regular abuse of cannabis there was no medical history of note. He had a sinus tachycardia (130 bpm), a slow pupillary reflex, bilateral hyposphagma and subcutaneous emphysema around the neck and shoulders. INVESTIGATIONS AND DIAGNOSIS: Laboratory tests showed elevated inflammatory markers. The chest X-ray demonstrated a bilateral pneumothorax and large subcutaneous emphysema. Subsequent computed tomography of neck and thorax showed an extensive pneumomediastinum and the described subcutaneous emphysema. There was no evidence of a ruptured trachea or esophageal perforation. The underlying cause was presumed to have been a Valsalva maneuver during marijuana smoking. TREATMENT AND COURSE: As the pneumothorax was completely reabsorbed, no chest drains were inserted and the patient was transferred to our toxicological intensive care unit. Recurring drug-induced psychosis had to be treated with repeated doses of haloperidol. The emphysema was slowly reabsorbed without any further complication. The patient was transferred back to a psychiatric ward after five days. CONCLUSION: Although cannabis is thought to be one of the "safe" drugs, its abuse can have life-threatening effects. One complication is the occurrence of a pneumothorax after a Valsalva maneuver. As the rate of cannabis abuse has been increasing during the last few years, the risk of life-threatening complications should be mentioned in relevant publications and as part of drug education. Patients presenting with dyspnea should always be carefully questioned about possible drug abuse. PMID- 17342633 TI - [Superior vena cava compression syndrome caused by mediastinal tumor space infiltration with invasion into the heart atrium and superior vena cava wall infiltration]. PMID- 17342634 TI - [Gene therapy strategies for colorectal cancer]. AB - Current advances in CRC treatment have led to significant but slight improvements in patient survival with curative outcomes only seen in earlier stage cancers. Consequently, much effort is being put into developing completely novel therapies that fulfil a number of criteria including greater efficacy and fewer side effects. Many of these conditions are met by the wide range of gene therapy strategies currently in pre-clinical or clinical trial phases. Gene therapy approaches may be broadly broken down into three main areas: Following a few tragic events in the context of clinical gene therapy studies, safety is currently the prime concern. Further progress in the field is expected from the combination of the described approaches with conventional treatment modalities. PMID- 17342635 TI - [Exenatide--an incretin-mimetic agent for the treatment of type 2 diabetes mellitus]. AB - The incretin hormone glucagon-like peptide 1 (GLP-1) is being synthesized from L cells in the gut and enhances glucose-induced insulin secretion. Metabolic control of type 2 diabetic patients can be markedly improved by additional administration of GLP-1, however, this peptide is almost immediately degraded and therefore has little clinical value. The synthetic GLP-1 agonist exenatide underlies a different metabolism and has recently been approved by the U.S. Food and Drug Administration for the adjunctive treatment of patients with type 2 diabetes who are suboptimally controlled with metformin and/or sulfonylurea. First controlled clinical trials provided evidence that glycaemic control under exenatide administered twice daily in a dose of 5-10 microg was not inferior to conventional insulin therapy. Novel aspects in the treatment of type 2 diabetes by GLP-1 receptor stimulation further include its influence on the insulin secretory pattern, insulin/glucagon ratio, body weight and possibly even pancreatic beta cell mass. However, a general application of exenatide in the treatment of type 2 diabetes will also largely depend on the therapy behavior of patients, a possible immunogenicity and the rate of adverse events. Furthermore, a possible indication for exenatide as first-line therapy of type 2 diabetes and the prognostic relevance of this novel therapeutic approach have yet to be defined. PMID- 17342636 TI - [Effects of LDL-apheresis--more than reduction of cholesterol?]. AB - LDL apheresis is a safe and very effective extracorporeal treatment of refractory hypercholesterolemia. LDL cholesterol levels can be reduced with this procedure by more than 60%. C-reactive protein (CRP) is a known marker of inflammation in atherosclerosis. Interestingly CRP can be effectively removed by a single LDL apheresis, but further studies are needed to substantiate the effect of extracorporeal reduction of CRP on the progression of atherosclerosis. However, adhesion molecules and activities of inflammatory cells were also found to be reduced after a single LDL apheresis. The biochemical composition of newly formed LDL particles after apheresis is altered: LDL particles isolated after LDL apheresis had an increased resistance to oxidative stress in vitro. In addition, antioxidants are not depleted by LDL apheresis. The extracorporal method itself does not have a negative impact on the oxidative/antioxidative balance. A recent investigation showed that LDL-cholesterol had a more pronounced effect on blood rheology than fibrinogen. This observation may explain why a single LDL apheresis leads to better myocardial perfusion, as demonstrated by PET in patients with hypercholesterolemia. These additional effects have so far only been known with statins. Further investigations are needed to substantiate the observed potentially beneficial effects of LDLapheresis beyond its effect of lowering LDL. PMID- 17342637 TI - Reemergence of anaerobic bacteremia. AB - BACKGROUND: During 1974-1988, the incidence of anaerobic bacteremia at the Mayo Clinic (Rochester, MN) decreased. This trend occurred nationally, prompting calls for discontinuation of routine anaerobic blood cultures. However, recently, the sites of anaerobic infection have been shown not to be as predictable as once thought, and since 1993, the incidence of anaerobic bacteremia has increased significantly in our medical center. METHODS: Records from the Mayo Clinic Division of Clinical Microbiology were used to tabulate the number of cases of anaerobic bacteremia in patients at the clinic for the 12-year period from 1993 through 2004. Medical records for patients with anaerobic bacteremia were reviewed from the periods of 1993-1994 and 2004 to identify differences between these 2 patient populations with different rates of bacteremia. RESULTS: The mean incidence of anaerobic bacteremias increased from 53 cases per year during 1993 1996 to 75 cases per year during 1997-2000 to 91 cases per year during 2001-2004 (an overall increase of 74%). The total number of cases of anaerobic bacteremia per 100,000 patient-days increased by 74% (P<.001). The number of anaerobic blood cultures per 1000 cultures performed increased by 30% (P=.002). Organisms from the Bacteroides fragilis group, other species of Bacteroides, and Clostridium species were most commonly isolated. CONCLUSIONS: Anaerobic bacteremia has reemerged as a significant clinical problem. Although there are probably multiple reasons for this change, the increasing number of patients with complex underlying diseases makes the clinical context for anaerobic infections less predictable than it once was. Anaerobic blood cultures should be routinely performed in medical centers with a patient population similar to ours. PMID- 17342638 TI - Routine anaerobic blood cultures: back where we started? PMID- 17342639 TI - Human bocavirus and acute wheezing in children. AB - BACKGROUND: Human bocavirus is a newly discovered parvovirus. It has been detected primarily in children with acute lower respiratory tract infection, but its occurrence, clinical profile, and role as a causative agent of respiratory tract disease are not clear. METHODS: We investigated the presence of human bocavirus by quantitative polymerase chain reaction of nasopharyngeal aspirate specimens and selected serum samples obtained from 259 children (median age, 1.6 years) who had been hospitalized for acute expiratory wheezing. The samples were analyzed for 16 respiratory viruses by polymerase chain reaction, virus culture, antigen detection, and serological assays. RESULTS: At least 1 potential etiologic agent was detected in 95% of children, and >1 agent was detected in 34% of children. Human bocavirus was detected in 49 children (19%). A large proportion of the cases were mixed infections with other viruses, but human bocavirus was the only virus detected in 12 children (5%). High viral loads of human bocavirus were noted mainly in the absence of other viral agents, suggesting a causative role for acute wheezing. In addition, infections that had uncertain clinical relevance and low viral loads were prevalent. Human bocavirus DNA was frequently detected in serum specimens obtained from patients with acute wheezing, suggesting systemic infection. CONCLUSIONS: Human bocavirus is prevalent among children with acute wheezing and can cause systemic infection. Results suggest a model for bocavirus infection in which high viral loads are potentially associated with respiratory symptoms and low viral loads indicate asymptomatic shedding. Therefore, quantitative polymerase chain reaction analysis may be important for additional studies of human bocavirus. PMID- 17342640 TI - Human bocavirus: a new viral pathogen. PMID- 17342641 TI - The management and outcome of spinal implant infections: contemporary retrospective cohort study. AB - BACKGROUND: Spinal implant infections provide unique diagnostic and therapeutic challenges. METHODS: We conducted a retrospective cohort study to evaluate risk factors for treatment failure in patients with early- and late-onset spinal implant infections at the Mayo Clinic (Rochester, MN) during 1994-2002. RESULTS: We identified 30 patients with early-onset spinal implant infection and 51 patients with late-onset spinal implant infection. Twenty-eight of 30 patients with early-onset infection were treated with debridement, implant retention, and antimicrobial therapy. The estimated 2-year cumulative probability of survival free of treatment failure for patients with early-onset infection was 71% (95% confidence interval [CI], 51%-85%). Thirty-two of 51 patients with late-onset infection were treated with implant removal. Their estimated 2-year cumulative probability of survival free of treatment failure was 84% (95% CI, 66%-93%). For patients with early-onset infections, receiving oral antimicrobial suppression therapy was associated with increased cumulative probability of survival (hazard ratio, 0.2; 95% CI, 0.1-0.7). For patients with late-onset infections, implant removal was associated with increased cumulative probability of survival (hazard ratio, 0.3; 95% CI, 0.1-0.7). CONCLUSIONS: Early-onset spinal implant infections are successfully treated with debridement, implant retention, and parenteral followed by oral suppressive antimicrobial therapy. Implant removal is associated with successful outcomes in late-onset infections. PMID- 17342642 TI - Antibiotic prophylaxis and the risk of surgical site infections following total hip arthroplasty: timely administration is the most important factor. AB - BACKGROUND: Surgical site infections (SSIs) following total hip arthroplasty can lead to prolonged hospitalization, increased morbidity and mortality, and high costs. This article analyzes the effect of various parameters of surgical antibiotic prophylaxis on the risk of SSI following total hip arthroplasty. METHODS: Data about SSI and potential prophylaxis-, patient-, and procedure related risk factors were prospectively collected for 1922 patients who underwent elective total hip arthroplasty in 11 hospitals that participated in the Dutch intervention project, Surgical Prophylaxis and Surveillance. Multivariate logistic regression analysis was performed to correct for random variation among hospitals. RESULTS: SSIs (superficial and deep) occurred in 50 patients (2.6%). The highest odds ratios for SSI were found in patients who received prophylaxis after incision (2.8, 95% confidence interval [CI], 0.9-8.6; P=.07), had an American Society of Anesthesiology score that was >2 (2.8, 95% CI, 0.8-9.2; P=.09), and experienced a duration of surgery that was >75th percentile (2.5; 95% CI, 1.1-5.8; P=.04). Prolonged prophylaxis after the end of surgery and the use of antibiotic-impregnated cement did not contribute to fewer SSIs in this study. CONCLUSIONS: This study suggests that intervention programs in search of amendable factors to prevent SSI should focus on timely administration of antibiotic prophylaxis. PMID- 17342643 TI - Prophylactic antibiotics: administration and timing before operation are more important than administration after operation. PMID- 17342644 TI - Tailored interventions to improve antibiotic use for lower respiratory tract infections in hospitals: a cluster-randomized, controlled trial. AB - BACKGROUND: Limited data exist on the most effective approach to increase the quality of antibiotic use for lower respiratory tract infections at hospitals. METHODS: One thousand nine hundred six patients with community-acquired pneumonia or an exacerbation of chronic obstructive pulmonary disease (acute exacerbation of chronic bronchitis) were included in a cluster-randomized, controlled trial at 6 medium-to-large Dutch hospitals. A multifaceted guideline-implementation strategy that was tailored to baseline performance and considered the barriers in the target group was used. Principal outcome measures were (1) guideline-adherent antibiotic prescription, (2) adaptation of dose and dose interval of antibiotics according to renal function, (3) switches in therapy, (4) streamlining of therapy, and (5) Gram staining and culture of sputum samples. Secondary process outcomes were applicable to community-acquired pneumonia (e.g., timely administration of antibiotics) or acute exacerbation of chronic bronchitis (e.g., not prescribing macrolides). RESULTS: The rate of guideline-adherent antibiotic prescription increased from 50.3% to 64.3% in the intervention hospitals (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.57-4.42; P=.0008). The rate of adaptation of antibiotic dose according to renal function increased from 79.4% to 95.1% in the intervention hospitals (OR, 7.32; 95% CI, 2.09-25.7; P=.02). The switch from intravenous to oral therapy improved more in the control hospitals (from 53.3% to 71.9%) than in the intervention hospitals (from 74% to 83.6%). The change from broad-spectrum empirical therapy to pathogen-directed therapy improved by 5.7% in the intervention hospitals (P = not significant). Fewer sputum samples were obtained from both the intervention group (rate of sputum samples obtained decreased from 55.8% to 53.1%) and the control group (rate of sputum samples obtained decreased from 49.6% to 42.7%). Timely administration of antibiotics for community-acquired pneumonia increased significantly in the intervention group (from 55.2% to 62.9%; OR, 2.49; 95% CI, 1.11-5.57; P=.026). CONCLUSIONS: With regard to some important aspects, tailoring interventions to change antibiotic use improved the quality of treatment for patients hospitalized with lower respiratory tract infection. PMID- 17342645 TI - Performance measurement in community-acquired pneumonia: consequences intended and unintended. PMID- 17342646 TI - A novel single-nucleotide polymorphism in the lactoferrin gene is associated with susceptibility to diarrhea in North American travelers to Mexico. AB - BACKGROUND: Diarrhea affects 40%-60% of travelers from industrialized nations who visit developing countries and is due to bacterial, viral, and parasitic agents. Lactoferrin is bactericidal to enteric pathogens, modulates the intestinal immune response, and is excreted in stool in response to infection with intestinal organisms. We investigated the impact that selected single-nucleotide polymorphisms (SNPs) in the human lactoferrin gene have on susceptibility to traveler's diarrhea. METHODS: Adults who had recently arrived in Mexico were studied prospectively for the occurrence and causal agent(s) of traveler's diarrhea, and genotyping was performed for 9 distinct lactoferrin SNPs. RESULTS: Of the 9 SNPs studied, only 1 SNP (located in exon 15) was associated with traveler's diarrhea (P=.004). When compared with healthy travelers, and after adjustment for known risk factors for traveler's diarrhea (such as age and duration and season of travel), subjects with the T/T genotype in amino acid position 632 were more likely to develop traveler's diarrhea (67% vs. 33%; relative risk [RR], 1.4; 95% CI, 1.2-1.7; P<.001), to have diarrhea with a pathogen identified (RR, 1.3; 95% CI, 1.1-1.6; P=.03), and to have a marker of intestinal inflammation in stool specimens (blood, mucus, or white blood cells; 52% vs. 38%; P=.036). The association was also significant when norovirus was not identified in stool samples (RR, 1.34; 95% CI, 1.06-1.34; P=.01). CONCLUSIONS: The T/T genotype in position codon 632 of the lactoferrin gene is associated with susceptibility to diarrhea in North Americans traveling to Mexico. PMID- 17342647 TI - Newest approaches to treatment of pelvic inflammatory disease: a review of recent randomized clinical trials. AB - Treatment of pelvic inflammatory disease (PID) should provide high rates of clinical and microbiological cure for a range of pathogens and should ultimately prevent reproductive morbidity. Between 1992 and 2006, 5 randomized clinical trials of moxifloxacin (1 trial), ofloxacin (1 trial), clindamycin-ciprofloxacin (1 trial), and azithromycin (2 trials) treatment among women with mild to moderate PID were found to have clinical cure rates of 90%-97%. Trials of ofloxacin and clindamycin-ciprofloxacin reported rates of cure of Neisseria gonorrhoeae and Chlamydia trachomatis infection of 100%, although microbiological cure data for other pathogens were not presented. One azithromycin trial reported a 98% eradication of C. trachomatis, N. gonorrhoeae, Mycoplasma hominis, and anaerobes. Moxifloxacin exhibited high eradication rates for N. gonorrhoeae, C. trachomatis, M. hominis, Mycobacterium genitalium, and gram-negative anaerobes. Clinical cure rates from 2 doxycycline-metronidazole trials were low (35% and 55%). Although a handful of studies have shown that monotherapies for PID achieve high rates of clinical cure, the efficacy of these regimens in treating anaerobic PID and in preventing adverse reproductive sequelae is not fully elucidated. PMID- 17342648 TI - Treatment of pelvic inflammatory disease. PMID- 17342649 TI - Neuraminidase inhibitors improve outcome of patients with leukemia and influenza: an observational study. AB - We reviewed the records of 33 patients with leukemia who experienced influenza during the period from October 2000 to March 2004. Three (38%) of the 8 patients who did not receive neuraminidase inhibitor therapy and none of the 25 patients who received it died of influenza pneumonia (P=.001). The use of neuraminidase inhibitor therapy seems to improve the outcome of influenza in patients with leukemia. PMID- 17342651 TI - Detection and spread of Escherichia coli possessing the plasmid-borne carbapenemase KPC-2 in Brooklyn, New York. AB - A carbapenem-resistant isolate of Escherichia coli was identified that possessed a 23-kb plasmid encoding Klebsiella pneumoniae carbapenemase type 2 (KPC-2). A subsequent surveillance study involving hospitals in Brooklyn, New York, revealed that, among 1417 E. coli isolates, 7 isolates (from 3 hospitals) possessed bla(KPC-2). E. coli possessing KPC-2 is emerging in our region, and improved methods for detection are urgently needed. PMID- 17342650 TI - A case of naturally acquired inhalation anthrax: clinical care and analyses of anti-protective antigen immunoglobulin G and lethal factor. AB - This report describes the first case of naturally acquired inhalation anthrax in the United States since 1976. The patient's clinical course included adjunctive treatment with human anthrax immunoglobulin. Clinical correlation of serologic assays for the lethal factor component of lethal toxin and anti-protective antigen immunoglobulin G are also presented. PMID- 17342652 TI - An HIV-positive man with slowly enlarging nodules on the extremities. PMID- 17342653 TI - Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story. AB - Campylobacter species cause 1.4 million infections each year in the United States. Fluoroquinolones (e.g., ciprofloxacin) are commonly used in adults with Campylobacter infection and other infections. Fluoroquinolones (e.g., enrofloxacin) are also used in veterinary medicine. Human infections with fluoroquinolone-resistant Campylobacter species have become increasingly common and are associated with consumption of poultry. These findings, along with other data, prompted the US Food and Drug Administration to propose the withdrawal of fluoroquinolone use in poultry in 2000. A lengthy legal hearing concluded with an order to withdraw enrofloxacin from use in poultry (effective in September 2005). Clinicians are likely to continue to encounter patients with fluoroquinolone resistant Campylobacter infection and other enteric infection because of the continued circulation of fluoroquinolone-resistant Campylobacter species in poultry flocks and in persons returning from foreign travel who have acquired a fluoroquinolone-resistant enteric infection while abroad. Judicious use of fluoroquinolones and other antimicrobial agents in human and veterinary medicine is essential to preserve the efficacy of these important chemotherapeutic agents. PMID- 17342654 TI - HIV epidemiology update and transmission factors: risks and risk contexts--16th International AIDS Conference epidemiology plenary. AB - The contexts in which the human immunodeficiency virus (HIV) pandemic is occurring are increasingly diverse. Individual-level risks for HIV infection are at the core of these epidemics and are powerfully impacted by social, structural, and population-level risks and protections. The emerging epidemics among injection drug users across Eurasia are largely the result of needle sharing, but the drivers of disease spread include increases in opiate availability, limited HIV infection prevention and programs for drug users, and undermining policy environments. An emerging epidemic of HIV infection among men who have sex with men in developing countries is primarily spread through unprotected anal intercourse but is also driven by limited HIV infection prevention services, social stigma, and the lack of human rights protection. The epidemic in southern Africa, which is spreading largely through heterosexual exposure, is driven by high rates of labor migration, concurrent sexual partnerships, gender inequalities, and the limited availability of male condoms. We need to do much more to control HIV infection, and social and structural risks are crucial intervention targets. PMID- 17342656 TI - Do HIV care providers appropriately manage hepatitis B in coinfected patients treated with antiretroviral therapy? AB - BACKGROUND: The common occurrence of hepatitis B virus (HBV) infection in patients who carry the human immunodeficiency virus (HIV) demands that both viruses be recognized, evaluated, and treated when appropriate. METHODS: We identified 357 HIV- and hepatitis B surface antigen-positive patients who underwent testing from 1999 to 2003; 155 patients who were new to our clinic and who initiated therapy for HIV and HBV coinfection were considered for inclusion in the study. The frequency of HIV testing (to determine HIV load and CD4+ cell count) performed during the first year of therapy was compared with the frequency of HBV measurements (to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load), abdominal ultrasound examination, and measurement of levels of alpha-fetoprotein in serum. RESULTS: HBV load data were obtained for only 16% of patients before initiation of antiretroviral therapy (ART), whereas HIV load was determined for 99% of patients before initiation of ART. The total number of HIV load measurements obtained during the first year after ART initiation was 497 (median number of HIV load measurements per patient, 3.0), compared with 85 measurements of HBV load (median number of HBV load measurements per patient, <1; P<.001). The percentage of patients who received any level of HBV monitoring (i.e., tests to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load) after ART initiation increased from 7% in 1999 to 52% in 2001 (P<.001), whereas the percentage of patients who underwent HIV load testing remained at 80%-90% during the same period. CONCLUSIONS: Health care providers treating patients with HIV infection during the period 1999-2003 infrequently monitored HBV response in coinfected patients, but they systematically monitored HIV response after ART initiation. Improved physician adherence to guidelines that better delineate HBV treatment and monitoring for patients with HIV-HBV coinfection is needed. PMID- 17342655 TI - Impact of hepatitis D virus infection on the long-term outcomes of patients with hepatitis B virus and HIV coinfection in the era of highly active antiretroviral therapy: a matched cohort study. AB - BACKGROUND: Triple infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis D virus (HDV) is rare. The influence of HDV infection on the responses to highly active antiretroviral therapy and hepatic complications in patients with HBV-HIV coinfection remains uncertain. METHODS: Twenty-six HDV-infected case patients and 78 HDV-uninfected matched control subjects were identified between 1 January 1995 and 30 June 2003. Clinical and immunologic outcomes were noted, and HBV and HIV loads and genotypic resistance of HBV to lamivudine were determined. RESULTS: Case patients had a higher rate of injection drug use (7.7% vs. 1.3%; P=.05) and lower serum levels of HBV DNA (median level, 4.04 vs. 5.75 log10 copies/mL; P=.07) than control subjects. During a median observation period of 54.7 months, HDV infection did not have an adverse impact on clinical, virological, or immunologic responses to highly active antiretroviral therapy. However, case patients had higher rates of hepatitis flares (57.7% vs. 23.1%; P=.002), hyperbilirubinemia (34.6% vs. 14.1%; P=.04), liver cirrhosis (26.9% vs. 5.1%; P=.009), hepatic decompensation (23.1% vs. 5.1%; P=.007), and death (adjusted hazard ratio, 5.41; 95% confidence interval, 1.39-23.85; P=.02), although these patients had a lower risk of genotypic resistance to lamivudine (0% vs. 57.1%; P=.003). CONCLUSIONS: HDV infection did not affect clinical, virological, or immunologic responses to highly active antiretroviral therapy in patients with HBV-HIV coinfection. HDV infection increased risk of hepatitis flares, liver cirrhosis, hepatic decompensation, and death in patients with HBV-HIV coinfection. PMID- 17342657 TI - Change over time in incidence of ganciclovir resistance in patients with cytomegalovirus retinitis. AB - BACKGROUND: In the mid-1990s, the incidence of cytomegalovirus (CMV) resistance to ganciclovir was estimated to be approximately 25% by 1 year after diagnosis of retinitis in patients with acquired immunodeficiency syndrome. METHODS: Two hundred fifty-seven patients with CMV retinitis were enrolled in a prospective observational study during 1993-2003 and were treated with ganciclovir. Demographic characteristics and data on CMV disease, antiretroviral therapy, and ganciclovir resistance were recorded for all patients. Human immunodeficiency virus (HIV) load and CMV load were measured for patients enrolled in 1996 or later. Kaplan-Meier and Cox proportional hazards regression methods were used to examine incidence of resistance. RESULTS: The 2-year incidence of resistance was 28% among patients enrolled before 1996 and 9% among those enrolled in or after 1996 (P=.001). All cases of resistance occurred among patients with CD4+ T cell counts <50 cells/microL, and positive CMV culture results at baseline were associated with a approximately 4-fold increase in resistance. Among patients whose CMV and HIV loads were measured, a detectable CMV load at baseline and during follow-up was associated with increased risk of resistance, but a detectable HIV load was not. CONCLUSIONS: Rates of resistance have decreased from the high levels seen in the pre-HAART era. Better control of CMV replication may have contributed to this decrease. PMID- 17342659 TI - Gammadelta T cells are associated with different infections and are Vdelta1+ or Vdelta2+ gammadelta T cells. PMID- 17342661 TI - Antiretroviral therapy for patients with HIV-hepatitis B virus coinfection. PMID- 17342663 TI - Management of women with cervicitis. AB - In the past several years, the collective understanding of cervicitis has extended beyond the recognition of Chlamydia trachomatis and Neisseria gonorrhoeae as the prime etiologic suspects. Trichomonas vaginalis and herpes simplex virus cause cervicitis, and both Mycoplasma genitalium and bacterial vaginosis have emerged as new candidate etiologic agents or conditions. However, major gaps in our knowledge of this common condition remain. Putative etiologic agents have not been identified in many women with cervicitis. Moreover, cervicitis occurs in a relatively small proportion of women with chlamydia or gonorrhea. Finally, scant research has addressed the clinical response of nonchlamydial and nongonococcal cervicitis to antibiotic therapy, and there are no data on the benefit of sex partner treatment for such women. New research into the etiology, immunology, and natural history of this common condition is needed, especially in view of the well-established links between cervicitis and an increased risk of upper genital tract infection and human immunodeficiency virus type 1 acquisition. PMID- 17342664 TI - Antibiotic therapy for acute pelvic inflammatory disease: the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. AB - Pelvic inflammatory disease (PID) is a substantial cause of reproductive morbidity in young women. A systematic review of the literature related to PID management was performed in preparation for the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. This search was conducted using PubMed and was limited to articles written in English and published between 1 January 2002 and 31 January 2005 that were related to PID treatment. Studies were evaluated for new data on PID with regard to site, route, and timing of antimicrobial administration; regimen adherence; experience in adolescents and women >35 years of age; coinfection with human immunodeficiency virus; and management of sex partners. Strong evidence suggests that neither site nor route of treatment administration affects the short- or long-term major outcome of women with mild or moderate clinical presentations. Data on these outcomes in women with more severe clinical presentations are inadequate to provide guidance as to the preferred agents or route of administration. Important contributions to the literature that impact the 2006 guidelines are described in this article. PMID- 17342665 TI - Trichomoniasis: challenges to appropriate management. AB - Trichomonas vaginalis infection is a common cause of vaginal irritation in women and is the most common nonviral sexually transmitted disease in the world. It has been associated with serious sequelae, the most notable of which are prematurity, low birth weight, and increases in human immunodeficiency virus transmission. We review advances in diagnosis and treatment and the current controversies regarding management. PMID- 17342666 TI - Current controversies in the management of adult syphilis. AB - Clinical management of patients with syphilis is controversial. This article summarizes recent research on syphilis treatment efficacy and outcomes and is based on a comprehensive systematic review of published literature, relevant abstracts, conference proceedings, technical reports, and guidelines. Penicillin remains the drug of choice for the treatment of syphilis. Although several studies have suggested that azithromycin may have clinical efficacy, macrolide resistance has been widely documented among strains of Treponema pallidum, and treatment failures have been reported. Ceftriaxone is effective for the treatment of syphilis when used in multiple-dose regimens. Lumbar puncture should be performed for human immunodeficiency virus-infected patients with syphilis of >1 year's duration and a serum nontreponemal test titer > or =1 : 32, as well for other patients for whom the clinical suspicion of neurosyphilis is high. Newer laboratory tests for syphilis are undergoing extensive evaluation and may prove to be useful for future clinical care. American and European approaches to syphilis treatment are similar, but they vary across several parameters. PMID- 17342667 TI - Treatment of lymphogranuloma venereum. AB - BACKGROUND: Lymphogranuloma venereum (LGV) classically presents with 1 or more genital ulcers or papules, as well as inguinal lymphadenopathy (buboes). Recently reported cases of LGV proctitis in men who have sex with men, many of whom are coinfected with human immunodeficiency virus (HIV), have highlighted the importance of optimal clinical treatment of LGV. METHODS: A review was conducted of the literature on LGV published between 1998 and 2004, as part of the development of the 2006 sexually transmitted disease treatment guidelines of the Centers for Disease Control and Prevention (CDC). RESULTS: Doxycycline (100 mg orally twice daily for 21 days) remains the treatment of choice for LGV. No controlled trials support the use of azithromycin or the use of alternative treatment regimens for persons with HIV infection. CONCLUSIONS: On the basis of the present literature review, the CDC's treatment recommendations for LGV remain unchanged. LGV clinical care, surveillance, and research are severely hindered by the lack of widely available, rapid, standardized tests for the diagnosis of LGV; therefore, patients with symptoms suggestive of LGV, including LGV proctitis, should be presumptively treated with antibacterial therapy for 3 weeks. PMID- 17342668 TI - Scabies and pediculosis pubis: an update of treatment regimens and general review. AB - Ectoparasites continue to be a common cause of skin disease throughout the world. The present article dissects the epidemiological profile and treatment of both Sarcoptes scabiei variant hominis and pediculosis pubis. PMID- 17342669 TI - Partner notification for sexually transmitted diseases. AB - Partner notification, a principal means of controlling sexually transmitted diseases, has traditionally been performed by public health professionals. They interview infected persons and contact the sex partners of these persons to notify them and convince them of the need to seek evaluation and treatment (known as "provider referral"). This notification method is labor intensive; the typical alternative to provider referral is to leave notification to the infected person (known as "patient referral"). However, innovations in partner notification, often created by public health professionals responsible for the practice, have yielded adjuncts and complements to both provider and patient referral. The present review article covers 4 areas of innovation: (1) enhancements to patient referral instructions and provider interview techniques, (2) use of the Internet in partner notification, (3) the emerging influence of network methods, and (4) expedited partner therapy, principally through patient-delivered medications or prescriptions. Partner notification remains necessary, and flexibility, openness to the use of multiple methods, and collaboration are likely to be helpful. PMID- 17342670 TI - Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. PMID- 17342671 TI - Management of uncomplicated Chlamydia trachomatis infections in adolescents and adults: evidence reviewed for the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. AB - In April 2005, in preparation for the 2006 Centers for Disease Control and Prevention (CDC) sexually transmitted diseases (STD) treatment guidelines, the CDC convened an advisory group to examine recent abstracts and published literature addressing management of Chlamydia trachomatis infections in adolescents and adults. Key questions were posed and answered on the basis of quality of evidence and expert opinion. Clinical trials continue to demonstrate equivalent efficacy and tolerability of azithromycin and doxycycline regimens, and both remain recommended as first-line therapy in nonpregnant individuals. More data and clinical experience are available to support the efficacy, safety, and tolerability of azithromycin in pregnant women, and, in the upcoming guidelines, azithromycin will be recommended as first-line therapy for such patients. Evidence is building that expedited partner therapy (EPT), with provision of treatment or a prescription, may be just as effective as or more effective than standard partner referral in ensuring partner treatment and preventing chlamydia recurrence in women. Although there are more studies needed and barriers to be addressed before its widespread use, EPT will be recommended as an option for partner management. PMID- 17342672 TI - Update on the management of gonorrhea in adults in the United States. AB - Gonorrhea, the second most commonly reported notifiable disease, is an important cause of cervicitis, urethritis, and pelvic inflammatory disease. The selection of appropriate therapy for gonorrhea (i.e., safe, highly effective, single dose, and affordable) is complicated by the ability of Neisseria gonorrhoeae to develop resistance to antimicrobial therapies. This article reviews the key questions and data that informed the 2006 gonorrhea treatment recommendations of the Centers for Disease Control and Prevention. Key areas addressed include the criteria used to select effective treatment for gonorrhea, the level of antimicrobial resistance at which changing treatment regimens is recommended, the epidemiology of resistance, and the use of quinolones, cephalosporins, and other classes of antimicrobials for the treatment of uncomplicated gonorrhea. PMID- 17342673 TI - [Some reflections on stroke treatment in South America]. PMID- 17342674 TI - [Factors associated to the visiting time in patients with ischaemic cerebrovascular disease]. AB - INTRODUCTION: The high prevalence of cerebrovascular disease in underdeveloped countries has made it a public health issue. Establishing therapy within the first three hours in the case of patients with cerebrovascular disease has proved to have beneficial effects on the patient. AIM: To identify the factors associated with the time taken to visit the hospital emergency department by patients with ischaemic cerebrovascular disease in the population of Colombia. PATIENTS AND METHODS: We conducted a cross-sectional analytical study that included patients over 18 years old who had been clinically diagnosed as having an acute ischaemic cerebrovascular disease. The time between onset of symptoms and admission to the emergency department was estimated and then related to sociodemographic and cultural factors and the severity of the clinical features. RESULTS: The mean time taken to visit hospital was 17 hours and 48 minutes (standard deviation: 24 hours and 12 minutes). In 22.8% of cases the patient was admitted within the first three hours. Patients who were covered by the subsidised health care system and came from low socioeconomic classes, together with those from rural areas took longer to visit (p < 0.005). The values on the United States Institute of Health scale did not have any relation to visiting times. CONCLUSIONS: The time that elapses between the presentation of the cerebrovascular disease and visiting the emergency department in the Colombian population is high, especially among the population with lower levels of income and schooling. There is a need to implement models of education targeted towards the community and focused on the early identification of signs, symptoms and impact of cerebrovascular disease, as well as to set up a system of health care that prevents delays by coordinating resources both inside and outside hospitals. PMID- 17342675 TI - [Factors associated with delayed hospital treatment for patients with acute cerebrovascular disease]. AB - INTRODUCTION: Cerebrovascular diseases are an important cause of morbidity and mortality in the world and the effectiveness of thrombolytic therapy depends on early intervention. AIMS: To determine the time taken for patients with acute cerebrovascular events to reach hospital and to observe the variables associated to a longer delay. PATIENTS AND METHODS: We conducted a retrospective, descriptive study of 151 patients treated for acute cerebrovascular events between September 2003 and September 2004 at the Hospital Nacional Cayetano Heredia (Lima, Peru). We searched the records for the time taken to reach hospital, demographic variables and cerebrovascular risk factors, and we observed whether they exerted a significant effect on the arrival time. RESULTS: It was found that 29.8% of patients with an acute cerebrovascular event go to hospital within the first three hours; the mean arrival time is 51.11 hours. In contrast, 51% of patients go to hospital after more than 12 hours. Taking three and six hours as the cut-off points, uni and multivariate analyses showed ischemic stroke to be linked to a longer delay; a diagnosis of atrial fibrillation is associated to a shorter delay in arrival time in the multivariate analysis if a cut-off time of three hours is taken into account. CONCLUSIONS: Despite the high percentage of patients who take a long time to visit hospital following a cerebrovascular event, approximately a third of the patients would benefit from early treatment with thrombolytic therapy. PMID- 17342676 TI - [Primary spinal cord tumours. An analysis of a series of 168 patients]. AB - INTRODUCTION: Primary intraspinal tumours comprise between 10 and 15% of all central nervous system tumours. Classically are classified into three groups, based on its location; namely: extradural, intradural extramedullary, and intramedurally spinal tumours. PATIENTS AND METHODS: We review retrospectively 173 intradural spinal tumours (in 168 patients) operated between 1980-2004. Age, sex, duration and type of symptoms, topographical locations, radiological and surgical results, histological features and outcome are analyzed. RESULTS: We treated 58 intramedullary tumours in 57 patients (34 female and 23 male). The mean age was 61.4 years-old. In 12 cases the tumour was sited in the cervical tract, 33 cases in the dorsal tract, and 13 in the lumbo-sacral tract. The most common histological types were ependimomas (26 cases) and astrocitoma (16 cases). Total removal of the lesion was possible in 36 patients (63.1%). In 111 patients the tumour were extramedullary (64 females and 47 males) with a mean age of 55.2 years-old. The most frequent location was the dorsal tract (63 cases) and the most common histological types were meningiomas (57 cases) and schwannomas (53 cases). Total removal of the lesion was possible in 109 patients (98.1%). CONCLUSIONS: Determinants predictors of a good outcome after surgery for spinal cord tumours are histological type of lesion, complete removal of the lesion, and a satisfactory neurological status before surgery. PMID- 17342677 TI - [Standardisation of a battery of tests to evaluate language comprehension, verbal fluency and naming skills in Brazilian children between 7 and 10 years of age: preliminary findings]. AB - INTRODUCTION: The neuropsychological assessment of language requires instruments that evaluate its receptive and expressive aspects. Due to cultural discrepancies, the use of neuropsychological tests demands normalization studies to the population in which they will be used. AIM: To provide normative data for Brazilian schoolchildren in relation to the Token Test, Semantic Verbal Fluency Test and the Minas Gerais Naming Test (animals, body parts and food categories). SUBJECTS AND METHODS: 101 children (51 males, 50 females) with ages between 7 to 10 years (mean: 8 years and 8 months), with 2 to 4 years of formal education. Exclusion criteria included score below 25 percentile in the Raven Test. RESULTS. There were no differences between male and female performance. Age was significantly related to performance in all tests. CONCLUSION: The results are compatible to the literature and, thought preliminary, they may be used as reference in research and clinical settings in our country. PMID- 17342678 TI - [Pontocerebellar hypoplasia type 1: a case report]. AB - INTRODUCTION: Pontocerebellar hypoplasias constitute a group of hereditary neurodegenerative disorders of uncertain aetiopathogenesis. They have been reported as being associated with deficiencies of complexes in the mitochondrial respiratory chain (MRC) and with congenital disorders of glycosylation. On the basis of clinical and neuropathological criteria, two phenotypes can be distinguished in this condition. Pontocerebellar hypoplasia type 1 is characterised by hypoplasia of the pons and the cerebellum associated with the degeneration of the motor neurons in the anterior horn of the spinal cord. CASE REPORT: A 4-year-old female with symptoms of severe psychomotor retardation associated with microcephaly, important generalised hypotonia, muscle hypotrophy, contractions in the four limbs, absence of stretch reflex and epilepsy with onset in the neonatal period. Magnetic resonance imaging of the brain revealed pontocerebellar hypoplasia. An electroneuromyography showed a trace that was compatible with axonal neuropathy and a biopsy of the deltoid muscle revealed the existence of neurogenic muscular atrophy. In the MRC study conducted in muscle homogenate and in skin fibroblasts, complex IV values were found to be at the lower limits of what could be considered to be normal levels. Results of the genetic study for spinal muscular atrophy were negative. CONCLUSIONS: The case reported here could be included as a case of pontocerebellar hypoplasia type 1. MRC studies can be of interest in cases of pontocerebellar hypoplasia in order to explain the role it plays in this disorder. PMID- 17342679 TI - [Protein arrays: applications and implications in neuroscience]. AB - INTRODUCTION: Genomics is bringing great advances into biomedical research that could help us to understand the physiopathology of diseases, and to find the features that differ disease from health. To understand the development of a given pathology, a global study is necessary that includes apart from the morphological and genomic study, analysis of protein interactions, the modifications that suffer their structure and even the changes in their concentration, as they are key molecules in the structure of the alive beings and in the execution of the biological processes. DEVELOPMENT: With the purpose of studying these aspects different technological boardings have been developed, protein arrays among them. These incorporate different methodologies, many of them are appropriate to detect postranscriptional modifications, and other ones are optimized for protein quantification. In this review different methodological boardings and the possible applications of those arrays are discussed. This tool is adapted for the comparative study of protein expression profiles of different structures and metabolic situations. The aim is to consider protein arrays like a tool to study the proteome in neuroscience. CONCLUSIONS: After validating biomarkers of clinical relevance discovered using protein arrays, this technology is a promising step in the road toward the development of early diagnosis protocols. To be able to validate the results, technological advance must be highlighted and an international consensus must be reached in different methodological aspects. These aspects will include normalisation and quantification of the signal produced. PMID- 17342680 TI - [Attentional impairment after traumatic brain injury: assessment and rehabilitation]. AB - INTRODUCTION: Attention disorders are a major problem after traumatic brain injury underlying deficits in other cognitive functions and in everyday activities, hindering the rehabilitation process and the possibility of return to work. Functional neuroimaging and neuropsychological assessment have depicted theoretical models considering attention as a complex and non-unitary process. DEVELOPMENT: Although there are conceptual difficulties, it seems possible to establish a theoretical background to better define attentional impairments and to guide the rehabilitation process. The aim of the present study is to review some of the most important pieces involved in the assessment and rehabilitation of attentional impairments. We also propose an appropriate model for the design of individualized rehabilitation programs. Lastly, different approaches for the rehabilitation are reviewed. CONCLUSIONS: Neuropsychological assessment should provide valuable strategies to better design the cognitive rehabilitation programs. It is necessary to establish a link between basic and applied neuropsychology, in order to optimize the treatments for traumatic brain injury patients. It is also emphasized that well-defined cognitive targets and skills are required, given that an unspecific stimulation of cognitive processes (pseudorehabilitation) has been shown to be unsuccessful. PMID- 17342681 TI - [The role of the human histocompatibility antigens in the pathogenesis of neurological disorders]. AB - INTRODUCTION: Several studies have been trying to define genetic markers of neurological disorders. Among them, antigens and alleles of the HLA (human leukocyte antigens) system are distinguished. The HLA exerts genetic influence on the susceptibility, clinical aspects and severity of many diseases. The discovery of new molecular methods to typify HLA alleles and the recent nomenclature updates have been contributing to a better understanding of this system. Unfortunately, this information has not been adequately published in the clinical literature. AIM: To review the structure, function, nomenclature and methods of detection of the HLA polymorphism and its associations with common neurological disorders. DEVELOPMENT: Articles that were published between 1990 and 2004 were searched in the MEDLINE and LILACS databases. This review demonstrated that although the HLA association is well established for some neurological disorders (e.g., HLA-DQB1*0602 with multiple sclerosis and narcolepsy; HLA-B7 e HLA-A2 with Alzheimer's disease; HLA-DR3-DR8 with Lamber-Eaton syndrome; and HLA class II Parkinson's disease and amyotrophic lateral sclerosis), these associations are not consistent and vary in different ethnic groups. CONCLUSIONS: It is necessary to study populations from different ethnic backgrounds to identify new associations or to strength the ones already identified. This knowledge will contribute in the evaluation of the risk that a person carrying a particular allele or haplotype has to develop a neurological disease and therefore contribute towards a better understanding of its pathogenesis. PMID- 17342682 TI - [Guidelines for the treatment of child spasticity using botulinum toxin]. AB - AIMS: The introduction of botulinum toxin has been a significant step forward in the treatment of spasticity in children and is now considered to be the preferred treatment in focal spasticity. With the aim of optimising this therapeutic resource, a group of Spanish neurologists and specialists in rehabilitation have drawn up these therapeutic guidelines based on the currently available evidence on its use and indications, and on their own experience. DEVELOPMENT: Spasticity in childhood is mainly caused by infantile cerebral palsy. Its natural history is not favourable due to the negative effect of growth and it should be treated before permanent deformities in bones and joints appear. Treatment with botulinum toxin diminishes hyperactivity and muscle tone, and allows the muscle to grow longitudinally, which prevents permanent contractions. The advantages of botulinum toxin are obvious (ease of use and dosing, long-lasting effects, reversibility in case of adverse responses, and so forth) and outnumber by far the few drawbacks it offers. Before it can be used patients, treatment goals and the muscle areas to be treated must all be selected correctly and, at the same time, a tailored rehabilitation scheme must also be developed. The growing body of experience suggests that its early administration is effective in preventing or reducing the severe complications of spasticity. CONCLUSIONS: Botulinum toxin type A is very effective in the treatment of spasticity. These guidelines offer the well-documented experience gained from its use and our knowledge about its indications, effects and safety in clinical practice. PMID- 17342684 TI - [Transient ischemic attack as an initial manifestation of painless acute aortic dissection]. PMID- 17342685 TI - [Rotavirus and its role in the genesis of afebrile seizures]. PMID- 17342686 TI - [The influence of oral anticoagulants in the natural history of cardioembolic cerebral infarctions]. PMID- 17342687 TI - [The brain mechanisms involved in making decisions: what exactly are we talking about?]. PMID- 17342688 TI - [Management of arteriovenous fistula: anastomosis and more....]. AB - The huge amount of human and economic resources necessary for a vascular access creation in haemodialysis strongly requires a very careful patient assessment and the choice of the most appropriate procedures, both aiming at improving quality of care and optimizing available resources. This review focuses on arteriovenous fistula (AVF) monitoring and surveillance, not only by following current guidelines, but also by exploring the most interesting data of the literature; attention is particularly focused on the haemodynamic aspects of AVF, which play a relevant role not only in himself. the natural history of vascular access, but also of the patient. PMID- 17342689 TI - [Anemia after renal transplantation]. AB - The anemia which commonly accompanies end-stage kidney disease usually remits within 10 - 16 weeks following successful kidney transplantation. However, a significant number of patients remain anemic or become anemic after transplantation. Unlike the great amount of data available on anemia in end-stage renal disease population, much less is known about post-transplant anemia (PTA). Existing literature data indicate that PTA prevalence is high; the findings of a few longitudinal studies showed a very high prevalence of PTA in the early post transplantation period; during the first 5-year post-transplant period, 30-40% of transplant patients are anemic, and PTA increases subsequently after transplantation. Available information suggests that PTA prevalence is higher in pediatric compared to adult patients. A decrease in renal allograft function has been identified in several studies as the most important risk factor for PTA development. Other common causes of PTA include iron deficiency, systemic illnesses, acute and chronic infections, and drug toxicities. Several reports indicate that PTA is associated with an increased cardiovascular disease risk. Although PTA is a frequent problem in transplanted patients, iron and erythropoietin therapy are even underused in this population. Erythropoietinis effective and safe in correcting anemia during both early and late post transplantation period. Prospective interventional studies in anemic kidney transplant recipients are needed to determine the most appropriate hemoglobin target in these patients and the potential beneficial role of erythropoietin therapy for cardiovascular and renal protection. PMID- 17342690 TI - [Hemolytic uremic syndrome]. AB - Hemolytic Uremic Syndrome (HUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytope-nia, and acute renal failure. HUS is most commonly triggered by Shiga-like toxin (Stx)-producing bacteria (Stx HUS). Non-Shiga toxin-associated HUS (non-Stx-HUS) affects a heterogeneous group of patients in whom an infection by Stx-producing bacteria can be excluded as cause of the disease. It can be sporadic or familial. Biochemical evidence suggested that alterations in the complement system play an important role in the pathological mechanisms of non-Stx-HUS. Subsequently, genetic studies have shown that the disease depends on the deficiency or abnormalities in complement regulatory proteins of the alternative pathway. About 30% of the patients have mutations in the gene encoding factor H (CFH); CFH is a protein that inhibits the activation of the alternative pathway of the complement system. More recent observations have also shown the involvement of genes that encode Membrane Cofactor Protein (MCP) and factor I (CFI). Genetic studies can be useful to improve therapeutic approach. Plasma infusion or plasma exchange are helpful treatments for patients with alterations in CFH or CFI, which are plasma proteins. On the other hand, plasma treatment in patients with alterations in MCP, a membrane-bound protein, does not impact the outcome significantly. Kidney transplantation outcome is favorable in patients with MCP mutations, whereas the outcome is poor in patients with CFH and CFI mutations due to disease recurrence. During the last years, genetic studies have allowed a better comprehension of pathological molecular mechanisms. The results will offer the rationale to develop new specific treatments for HUS. PMID- 17342691 TI - [Anticoagulation of extracorporeal circuit in critically ill patients]. AB - Heparin is currently the most popular anticoagulant for extracorporeal circuits in ICUs. Yet, heparin may also be considered as an invasive procedure possibly complicated by bleeding in post-surgical patients who are often septic and with largely exposed skin areas. Over time many alternatives in anticoagulation have been suggested and applied with varying outcomes, including both systemic (heparinoids, thrombin inhibitors, nafamostat, prostacyclin) and regional (saline flushes, protamin coupled heparin, cit-rate). Among all, citrate is emerging as the most promising method with regard to efficacy, safety and feasibility, beside its being more and more used, particularly in North America and northern European countries. Many reasons could explain this success, such as low costs, uncomplicated technology, easy handling and complete reversibility of its anticoagulant activity. Above all, the main advantage of citrate is its capacity to provide anticoagulation specific to the extracorporeal circuit with-out involving the patient. In critically ill patients the bleeding rate is more frequent in continuous than in intermittent treatments, and the bleeding risk is often per se the main factor hindering the practical feasibility of ''continuous'' treatment. PMID- 17342692 TI - [Withdrawing or discontinuing chronic dialysis in adult patients]. AB - Dialysis treatment leads chronic uremic patients to a prolonged survival; incidence and prevalence of dialysis patients are increasing, the population is getting older and many comorbidities coexist, such as diabetes, heart diseases, vasculopathies, neoplasia. The question often arises of whether to start or continue dialysis treatment in compromised patients. Withdrawing and/or discontinuing dialysis represents a therapeutic option with different ratios among countries, due to various cultural, religious, legal and social aspects. Italy shows a low prevalence, but a future increase is likely to appear. The crucial issue is the doctor-patient relationship: thanks to recent legal regulations, the patient has started to play an active role in the therapeutic decision making, by signing or not the informed consent regarding the therapeutic options suggested. In the Piemonte Region we evaluated the behavior of the nephrology operating units, through a consultant- and head nurses team-oriented survey. Most interviewees assert that starting a dialysis treatment is not always mandatory for every patient. The choice of per-forming dialysis should always be based on patient informed consent and in agreement with the physician in charge, the family and the patient himself. It is fundamental to choose to discontinue dialysis consistently with patients' prognosis and their concept of quality of life. It is mostly believed to be a legal and deontological duty to continue dialysis treatment, should any clear patient's will declaration lack. PMID- 17342693 TI - [Hyperhomocysteinemia and alternate vitamin supplementation]. AB - BACKGROUND: Treatment with folic acid and vitamin B 12 appears to be effective in lowering total plasma Homocysteine (tHcy) concentration, but whether vitamin B 12 alone decreases tHcy in patients with normal vitamin B 12 status is still unknown. The aims of the present study were to explore the effect of alternate vitamin supplementation with folic acid or vitamin B 12 on tHcy concentrations in haemodialysis (HD) patients, and to compare changes in tHcy concentrations with MTHFR genotype. METHODS: 74 patients, 44 men and 30 women, were recruited and randomized blindly into two groups of 37 subjects each. The first group was initially treated with vitamin B 12 for two months, and with folic acid for the following two months; the second group was supplemented in the reverse order. In both groups the treatment was followed by a 2-month washout period. tHcy levels were measured at the beginning of treatment (T0), after two months (T1), four months (T2), and at the end of the washout period (T3). Vitamin B 12 and folate were taken at T0 and T3. RESULTS: The genotype frequency was: C/C 37%, C/T 34%, T/T 29%. tHcy decreased in both groups following the alternate vitamins therapy. This decrease was greater for the T/T genotype (p<0.05) and was more significant when the treatment start-ed with folic acid (p<0.01). Moreover, after the washout period, tHcy increased remarkably without significant differences between diffusive and convective techniques. Folate levels at the end of study appeared to be reduced in haemodialysis patients. Vitamin B 12 concentration significantly increased in patients on diffusive haemodialysis, confirming the fundamental role of membrane performance. CONCLUSION: The alternate vitamin treatment demonstrated the importance of folate therapy and the secondary contribution of vitamin B 12 in lowering tHcy in HD patients. PMID- 17342694 TI - [Femoral arteriovenous fistula: a late uncommon complication of central venous catheterization]. AB - A 77-year-old woman was admitted due to AV graft thrombosis; given the technical impossibility of performing other native AV fistulas, we chose to insert a tunnelled central venous catheter. Considering the vascular history of the patient, the central venous catheter could not be placed into the internal jugular vein; it was therefore put into the left femoral vein. Following a 3 month-period of the catheter working properly, the patient was hospitalized due to sudden acute pain in the left thigh. In a few days the patient developed an important haematoma with serious anemization in the left lower limb. Ultrasonography showed the presence of a fistula between the left common femoral artery and the femoral vein, leading to the subsequent successful positioning of a stent into the common femoral artery through right trans-femoral access. Angiography examination showed the femoral vein patency along the proximal stretch with respect to the function of the tunnelled venous catheter. PMID- 17342695 TI - [Confounding and interaction in multiple regression]. AB - In multiple regression the effect of an input (independent) variable on a continuous output (dependent or response) variable can be adjusted for the effect of confounding and modifying variables. This adjustment is useful to obtain either an unbiased estimate of the true association between an exposure and an outcome or to predict the outcome for given inputs after removing the influence of other factors. These factors are defined as confounders if they are associated with the exposure and are independent risk factors for the outcome, without being intermediates on the biological pathway between exposure and outcome. An interaction between exposure and another independent variable is present when the exposure-disease relationship varies across different values of this variable. Multivariable regression modeling removes the association between the confounder and the outcome eliminating the necessary condition for confounding. An interaction term can be also incorporated into the model to quantify any potential modifying effect. PMID- 17342696 TI - [A tricky issue for the ultrasound technician]. AB - A 72-year-old woman presented with chronic renal failure and diffuse abdominal pain. On ultrasonography the right kidney showed an uncommon site, whereas the left kidney presented a pseudo mass on its lower pole. MRI detected a multiple anatomic anomaly: dislocation of the right kidney, renal fusion, malrotation of the left kidney. This anatomic anomaly is called ''sigmoid kidney'': it can be asymptomatic or result in genitourinary diseases. PMID- 17342697 TI - [Urinalysis in Italy in 2006]. AB - Urinalysis and proteinuria testing represent fundamental tests for the clinician, even though they too often lack standardization. Through the Italian Society of Nephrology Mailing List we sent a questionnaire to 282 centers, in order to assess the state of the art in Italy in the year 2006. 82% of the questionnaires were completed (nephrology laboratories: 64%, general laboratories: 36%). The questionnaire dealt with the main steps of preparation, analysis and report of urinalysis, and proteinuria / microalbuminuria measurement. 85% of the centers use first morning urine, and 7% second morning urine; only 57% of the centers supply with written instructions, 189 laboratories (82%) have only one bright field microscope, rate and time of centrifugation are very varied among centers, different units of measurement are used in reports. Few laboratories measure routinely the proteinuria / creatininuria ratio, there is no agreement on the urine sample type for microalbuminuria assay, total urinary proteins are measured through different methods. 92% of the centers is endowed with an internal quality control system, but only 47% participate in an external quality control program. These data confirm the lack of standardization for urine analysis methods and procedures. PMID- 17342699 TI - Three p-value consistent procedures for multiple comparisons with a control in direction-mixed families. AB - In clinical studies, it is common to compare several treatments with a control. In such cases, the most popular statistical technique is the Dunnett procedure. However, the Dunnett procedure is designed to deal with particular families of inferences in which all hypotheses are either one sided or two sided. Recently, based on the minimization of average simultaneous confidence interval width, a single-step procedure was derived to handle more general inferential families that contained a mixture of one- and two-sided inferences. But that single-step procedure is unable to guarantee the condition of p-value consistency which means that when a hypothesis with a certain p-value is rejected, all other hypotheses with smaller p-values are also rejected. In this paper, we present a single-step procedure and two stepwise procedures which are p-value consistent. The two proposed stepwise procedures provide more powerful testing methods when compared with single-step procedures. The extent of their superiority is demonstrated with a simulation study of average power. Selected critical values are tabulated for the implementation of the three proposed procedures. Additional simulation studies provide evidence that the new stepwise procedures are robust to moderate changes in the underlying probability distributions, and the proposed step-up procedure is uniformly more powerful than the resampling-based Hochberg step-up approach in all considered distribution models. Finally, we provide a practical example with sample data extracted from a medical experiment. PMID- 17342698 TI - [MEN type 1 and chronic renal failure: a rarely reported association]. AB - BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1), or Wermer's syndrome, is a rare autosomal dominant genetic syndrome characterized by tumors or hyperplasia involving the pituitary, parathyroid, and pancreatic islet cells. Association between MEN 1 and nephrocalcinosis is well known, though data published in medical literature regarding Wermer's syndrome and chronic renal failure relation are still rare. CASE: A 70-year-old Caucasian female patient had a history of primitive hyperparathyroidism, prolactinoma, glucagonoma, adrenal adenoma and pulmonary neuroendocrine neoplasia. She presented at our clinic first when she was 62 years old because of hypertension, nephrolithiasis (calcium oxalate) and diabetes mellitus treated with oral agents. During the eight-year follow-up she developed chronic renal failure (serum creatinine 1.8 mg/dL, glomerular clearance 35 mL/min) and partial thrombosis of abdominal aortic wall. CONCLUSIONS: Although the association between renal failure and MEN 1 is rarely reported, patients affected by Wermer's syndrome have several risk factors of decreasing renal function such as hypertension, nephrolithiasis and diabetes mellitus. Moreover, hyperparathyroidism in MEN 1 is clinically similar to the kidney failure condition; indeed, diffuse hyper-plasia of more than one gland is common. Vitamin D should not be administered to these patients. Nephrologists should be involved in MEN 1 follow-up, with the aim to prevent kidney failure development by correcting risk factors. PMID- 17342700 TI - Correlation analysis for longitudinal data: applications to HIV and psychosocial research. AB - Correlation analysis is widely used in biomedical and psychosocial research for assessing rater reliability, precision of diagnosis and accuracy of proxy outcomes. The popularity of longitudinal study designs has propelled the proliferation in recent years of new methods for longitudinal and other multi level clustered data designs, such as the mixed-effect models and generalized estimating equations. Despite these advances, research and methodological development on addressing missing data for correlation analysis is woefully lacking. In this paper, we consider non-parametric inference for the product moment correlation within a longitudinal data setting and address missing data under both the missing completely at random and missing at random assumptions. We illustrate the approach with real study data in mental health and HIV prevention research. PMID- 17342701 TI - Origin of intrinsic 3(10)-helix versus strand stability in homopolypeptides and its implications for the accuracy of the Amber force field. AB - Current all-atom force fields often fail to recognize the native structure of a protein as the lowest free energy minimum. One possible cause could be the mathematical form of the potential based on the assumption that the conformation of a residue is independent of its neighbors. Here, using quantum mechanical (QM) methods (MP2/6-31g**//HF/6-31g** and MP2/cc-pVDZ//cc-pVDZ//HF/cc-pVDZ), the intrinsic correctness of the gas phase terms (without solvation) of the Amber ff03 and ff99 potentials are examined by testing their ability to reproduce the relative 3(10)-helix versus extended structure stabilities in the gas phase for 1 7-residue alanine, valine, leucine, and isoleucine homopolypeptides. The 3(10) helix versus extended state stability strongly depends on chain length and less on the amino acid identity. The helical conformation becomes lower in energy than the extended conformation for all tested peptides longer than two residues, and its stability increases with the increase of chain length. The ff03 potential better describes the 3(10)-helix versus extended state energy than ff99 and also reproduces the curvature of the relative helix-extended state energies. Therefore, the mathematical form of the Amber potential is sufficient to describe the local effect of 3(10)-helix versus extended structure stabilization in the gas phase. However, the energy curves are shifted and the backbone geometries differ compared with the QM results. This may cause significant geometric discrepancies between native and predicted structures. Therefore, extant molecular mechanics force fields, such as Amber, need refinement of their parameters to correctly describe helix-extended state energetics and geometry of major conformations. PMID- 17342702 TI - Molecular structures of the two most stable conformers of free glycine. AB - The equilibrium molecular structures of the two lowest-energy conformers of glycine, Gly-Ip and Gly-IIn, have been characterized by high-level ab initio electronic structure computations, including all-electron cc-pVTZ CCSD(T) geometry optimizations and 6-31G* MP2 quartic force fields, the latter to account for anharmonic zero-point vibrational effects to isotopologic rotational constants. Based on experimentally measured vibrationally averaged effective rotational constant sets of several isotopologues and our ab initio data for structural constraints and zero-point vibrational shifts, least-squares structural refinements were performed to determine improved Born-Oppenheimer equilibrium (r(e)) structures of Gly-Ip and Gly-IIn. Without the ab initio constraints even the extensive set of empirical rotational constants available for 5 and 10 isotopologues of Gly-Ip and Gly-IIn, respectively, cannot satisfactorily fix their molecular structure. Excellent agreement between theory and experiment is found for the rotational constants of both conformers, the rms residual of the final fits being 7.8 and 51.6 kHz for Gly-Ip and Gly-IIn, respectively. High-level ab initio computations with focal point extrapolations determine the barrier to planarity separating Gly-IIp and Gly-IIn to be 20.5 +/- 5.0 cm(-1). The equilibrium torsion angle tau(NCCO) of Gly-IIn, characterizing the deviation of its heavy-atom framework from planarity, is (11 +/- 2) degrees. Nevertheless, in the ground vibrational state the effective structure of Gly-IIn has a plane of symmetry. PMID- 17342703 TI - Can an OH radical form a strong hydrogen bond? A theoretical comparison with H2O. AB - In this study, we apply UCCSD/6-31++G** to investigate the ability of an OH radical acting as a hydrogen bond acceptor with HF, HCl, and H(2)O (HO...HX; X=F, Cl, OH) or as a hydrogen bond donor with H(2)O and H(2)S (OH...XH(2); X=O and S). We also replace OH with H(2)O and make a fair comparison between them. Additionally, the counterpoise method (CP) has been used to examine the effect of basis set superposition error (BSSE). Our results reveal that OH is a stronger hydrogen bond donor but a weaker hydrogen bond acceptor than H(2)O. This conclusion is independent of the correction for BSSE and can be rationalized by the NBO analysis, the results of which indicate that OH radical has a lower n(O) and sigma*(O-H) in energy than that of H(2)O. PMID- 17342704 TI - Theoretical studies on farnesyl transferase: evidence for thioether product coordination to the active-site zinc sphere. AB - Farnesyltransferase (FTase), an interesting zinc metaloenzyme, has been the subject of great attention in anticancer research over the last decade. However, despite the major accomplishments in the field, some very pungent questions on the farnesylation mechanism still persist. In this study, the authors have analyzed a mechanistic paradox that arises from the existence of several contradicting and inconclusive experimental evidence regarding the existence of direct coordination between the active-site zinc cation and the thioether from the farnesylated peptide product, which include UV-vis spectroscopy data on a Co(2+)-substituted FTase, two X-ray crystallographic structures of the FTase product complex, and extended X-ray absorption fine structure results. Using high level theoretical calculations on two models of different sizes, and QM/MM calculations on the full enzyme, the authors have shown that the farnesylated product is Zn coordinated, and that a subsequent step where this Zn bond is broken is coherent with the available kinetic results. Furthermore, an explanation for the contradicting experimental evidence is suggested. PMID- 17342705 TI - Vertical excitation energies for ribose and deoxyribose nucleosides. AB - Vertical excitation energies for DNA and RNA nucleosides are determined with electron structure calculations using the time-dependent density functional theory (TDDFT) method at the B3LYP/6-311++G(d,p) level for nucleoside structures optimized at the same level of theory. The excitation energies and state assignments are verified using B3LYP/aug-cc-pVDZ level calculations. The nature of the first four excited states of the nucleosides are studied and compared with those of isolated bases. The lowest npi* and pipi* transitions in the nucleoside remain localized on the aromatic rings of the base moiety. New low-energy npi* and pisigma* transitions are introduced in the nucleosides as a result of bonding to the ribose and deoxyribose molecules. The effect on the low-lying excited state transitions of the binding to phosphate groups at the 5'- and 3',5' hydroxyl sites of the uracil ribose nucleoside are also studied. Some implications of these calculations on the de-excitation dynamics of nucleic acids are discussed. PMID- 17342706 TI - Hybrid molecular dynamics-quantum mechanics simulations of solute spectral properties in the condensed phase: evaluation of simulation parameters. AB - We have explored the impact of a number of basic simulation parameters on the results of a recently developed hybrid molecular dynamics-quantum mechanics (MD QM) method (Mercer et al., J Phys Chem B 1999, 103, 7720). The method utilizes MD simulations to explore the ground-state configuration space of the system and QM evaluation of those structures to yield the time-dependent electronic transition energy, which is transformed into the optical line-broadening function using the second-order cumulant expansion. Both linear and nonlinear optical spectra can then be generated for comparison to experiment. The dependence of the resulting spectra on the length of the MD trajectory, the QM sampling rate, and the QM model chemistry have all been examined. In particular, for the system of oxazine 4 in methanol studied here, at least 20 ps of MD trajectory are needed for qualitative convergence of linear spectral properties, and >100 ps is needed for quantitative convergence. Surprisingly, little difference is found between the 3 21G and 6-31G(d) basis sets, and the CIS and TD-B3LYP methods yield remarkably similar spectra. The semiempirical INDO/s method yields the most accurate results, reproducing the experimental Stokes shift to within 5% and the FWHM to within 20%. Nonlinear 3-pulse photon echo peak shift (3PEPS) decays have also been simulated. Decays are generally poorly reproduced, though the initial peak shift which depends on the overall coupling of motions to the solute transition energy is within 15% of experiment for all model chemistries other than those using the STO-3G basis. PMID- 17342707 TI - Backbone building from quadrilaterals: a fast and accurate algorithm for protein backbone reconstruction from alpha carbon coordinates. AB - In this contribution, we present an algorithm for protein backbone reconstruction that comprises very high computational efficiency with high accuracy. Reconstruction of the main chain atomic coordinates from the alpha carbon trace is a common task in protein modeling, including de novo structure prediction, comparative modeling, and processing experimental data. The method employed in this work follows the main idea of some earlier approaches to the problem. The details and careful design of the present approach are new and lead to the algorithm that outperforms all commonly used earlier applications. BBQ (Backbone Building from Quadrilaterals) program has been extensively tested both on native structures as well as on near-native decoy models and compared with the different available existing methods. Obtained results provide a comprehensive benchmark of existing tools and evaluate their applicability to a large scale modeling using a reduced representation of protein conformational space. The BBQ package is available for downloading from our website at http://biocomp.chem.uw.edu.pl/services/BBQ/. This webpage also provides a user manual that describes BBQ functions in detail. PMID- 17342708 TI - Quick scheme for evaluation of atomic charges in arbitrary aluminophosphate sieves on the basis of electron densities calculated with DFT methods. AB - It is demonstrated that unique and simple analytical functions are justified for the atomic charge dependences q of the T (T = Al, P) and O atoms of aluminophosphates (AlPOs) using DFT calculations with several basis sets, starting from STO-3G to 3-21G and 6-21G**. Three internal (bonds, angles, ...) coordinates for the charge dependences of the T atoms and four coordinates for the O are sufficient to reach a precision of 1.8% for the fitted q(Al), 1.0% for q(P), and 2.5% for q(O) relatively to the values calculated at any basis set level. The proposed strategy consists in an iterative scheme starting from charge dependences based on the neighbor's positions only. Electrostatic potential values are computed to illustrate the differences between the calculated and fitted charges in the considered AlPO models. PMID- 17342709 TI - Protein structure prediction: combining de novo modeling with sparse experimental data. AB - Routine structure prediction of new folds is still a challenging task for computational biology. The challenge is not only in the proper determination of overall fold but also in building models of acceptable resolution, useful for modeling the drug interactions and protein-protein complexes. In this work we propose and test a comprehensive approach to protein structure modeling supported by sparse, and relatively easy to obtain, experimental data. We focus on chemical shift-based restraints from NMR, although other sparse restraints could be easily included. In particular, we demonstrate that combining the typical NMR software with artificial intelligence-based prediction of secondary structure enhances significantly the accuracy of the restraints for molecular modeling. The computational procedure is based on the reduced representation approach implemented in the CABS modeling software, which proved to be a versatile tool for protein structure prediction during the CASP (CASP stands for critical assessment of techniques for protein structure prediction) experiments (see http://predictioncenter/CASP6/org). The method is successfully tested on a small set of representative globular proteins of different size and topology, including the two CASP6 targets, for which the required NMR data already exist. The method is implemented in a semi-automated pipeline applicable to a large scale structural annotation of genomic data. Here, we limit the computations to relatively small set. This enabled, without a loss of generality, a detailed discussion of various factors determining accuracy of the proposed approach to the protein structure prediction. PMID- 17342710 TI - Polarizable model potential function for nucleic acid bases. AB - A polarizable model potential (PMP) function for adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U) is developed on the basis of ab initio molecular orbital calculations at the MP2/6-31+G* level. The PMP function consists of Coulomb, van der Waals, and polarization terms. The permanent atomic charges of the Coulomb term are determined by using electrostatic potential (ESP) optimization. The multicenter polarizabilities of the polarization term are determined by using polarized one-electron potential (POP) optimization in which the electron density changes induced by a test charge are target. Isotropic and anisotropic polarizabilities are adopted as the multicenter polarizabilities. In the PMP calculations using the optimized parameters, the interaction energies of Watson-Crick type A-T and C-G base pairs were -15.6 and -29.4 kcal/mol, respectively. The interaction energy of Hoogsteen type A-T base pair was -17.8 kcal/mol. These results reproduce well the quantum chemistry calculations at the MP2/6-311++G(3df,2pd) level within the differences of 0.6 kcal/mol. The stacking energies of A-T and C-G were -9.7 and -10.9 kcal/mol. These reproduce well the calculation results at the MP2/6-311++G (2d,2p) level within the differences of 1.3 kcal/mol. The potential energy surfaces of the system in which a sodium ion or a chloride ion is adjacent to the nucleic acid base are calculated. The interaction energies of the PMP function reproduced well the calculation results at the MP2/6-31+G* or MP2/6-311++G(2d,2p) level. The reason why the PMP function reproduces well the high-level quantum mechanical interaction energies is addressed from the viewpoint of each energy terms. PMID- 17342712 TI - Chemical graph theory and n-center electron delocalization indices: a study on polycyclic aromatic hydrocarbons. AB - Relations between aromaticity indices derived from chemical graph theory and those based on 6-center electron delocalization are investigated for a series of polybenzenoid hydrocarbons. Aromatic stabilization obtained by means of the effective scaled electron delocalization is highly correlated to the resonance energy, RE, obtained both from SCF MO calculations and conjugated ring circuits model. Local aromaticity of benzene rings is discussed using two different criteria, in one of them aromaticity is just given by the cyclic pi-electron conjugation of the ring, whereas terms involving more than one ring are also considered in the other one. Indices derived from chemical graph theory and those obtained from the 6-center electron delocalization give rise to the same local aromaticity. Moreover, 6-center electron delocalization provides more quantitative information. PMID- 17342711 TI - Energy landscapes of nucleophilic substitution reactions: a comparison of density functional theory and coupled cluster methods. AB - We have carried out a detailed evaluation of the performance of all classes of density functional theory (DFT) for describing the potential energy surface (PES) of a wide range of nucleophilic substitution (SN2) reactions involving, amongst others, nucleophilic attack at carbon, nitrogen, silicon, and sulfur. In particular, we investigate the ability of the local density approximation (LDA), generalized gradient approximation (GGA), meta-GGA as well as hybrid DFT to reproduce high-level coupled cluster (CCSD(T)) benchmarks that are close to the basis set limit. The most accurate GGA, meta-GGA, and hybrid functionals yield mean absolute deviations of about 2 kcal/mol relative to the coupled cluster data, for reactant complexation, central barriers, overall barriers as well as reaction energies. For the three nonlocal DFT classes, the best functionals are found to be OPBE (GGA), OLAP3 (meta-GGA), and mPBE0KCIS (hybrid DFT). The popular B3LYP functional is not bad but performs significantly worse than the best GGA functionals. Furthermore, we have compared the geometries from several density functionals with the reference CCSD(T) data. The same GGA functionals that perform best for the energies (OPBE, OLYP), also perform best for the geometries with average absolute deviations in bond lengths of 0.06 A and 0.6 degrees, even better than the best meta-GGA and hybrid functionals. In view of the reduced computational effort of GGAs with respect to meta-GGAs and hybrid functionals, let alone coupled cluster, we recommend the use of accurate GGAs such as OPBE or OLYP for the study of SN2 reactions. PMID- 17342713 TI - Molecular dynamics simulation of single wall carbon nanotubes polymerization under compression. AB - Single wall carbon nanotubes (SWCNTs) often aggregate into bundles of hundreds of weakly interacting tubes. Their cross-polymerization opens new possibilities for the creation of new super-hard materials. New mechanical and electronic properties are expected from these condensed structures, as well as novel potential applications. Previous theoretical results presented geometric modifications involving changes in the radial section of the compressed tubes as the explanation to the experimental measurements of structural changes during tube compression. We report here results from molecular dynamics simulations of the SWCNTs polymerization for small diameter arm chair tubes under compression. Hydrostatic and piston-type compression of SWCNTs have been simulated for different temperatures and rates of compression. Our results indicate that large diameter tubes (10,10) are unlike to polymerize while small diameter ones (around 5 A) polymerize even at room temperature. Other interesting results are the observation of the appearance of spontaneous scroll-like structures and also the so-called tubulane motifs, which were predicted in the literature more than a decade ago. PMID- 17342714 TI - Finding the transition state without initial guess: the growing string method for Newton trajectory to isomerization and enantiomerization reaction of alanine dipeptide and poly(15)alanine. AB - We report a new, high-dimensional application of a method for finding a transition state (TS) between a reactant and a product on the potential energy surface: the search of a growing string along a reaction path defined by any Newton trajectory in combination with the Berny method (Quapp, J Chem Phys (2005), 122, 174106; we have provided this algorithm on a web page). Two given minima are connected by a one-dimensional, but usually curvilinear reaction coordinate. It leads to the TS region. The application of the method to alanine dipeptide finds the TS of the isomerisation C(7 ax) --> C(5), some TSs of the enantiomerisation of C(7 ax) from L-form to quasi-D-form, and it finds the TS region of a transition of a partly unfolded, bent structure which turns back into a mainly alpha-helix in the Ac(Ala)(15)NHMe polyalanine (all at the quantum mechanical level B3LYP/6-31G: the growing string calculation is interfaced with the Gaussian03 package). The formation or dissolvation of some alpha- or 3(10) hydrogen bonds of the helix are discussed along the TS pathway, as well as the case of an enantiomer at the central residue of the helix. PMID- 17342715 TI - Quantum mechanical charge field molecular dynamics simulation of the TiO2+ ion in aqueous solution. AB - Structural and dynamical properties of the TiO(2+) ion in aqueous solution have been investigated by using the new ab initio quantum mechanical charge field (QMCF) molecular dynamics (MD) formalism, which does not require any other potential functions except those for solvent-solvent interactions. Both first and second hydration shell have been treated at Hartree-Fock (HF) quantum mechanical level. A Ti-O bond distance of 1.5 A was observed for the [Ti=O](2+) ion. The first hydration shell of the ion shows a varying coordination number ranging from 5 to 7, five being the dominant one and representing one axial and four equatorial water molecules directly coordinated to Ti, which are located at 2.3 A and 2.1 A, respectively. The flexibility in the coordination number reflects the fast exchange processes, which occur only at the oxo atom, where water ligands are weakly bound through hydrogen bonds. Considering the first shell hydration, the composition of the TiO(2+) hydrate can be characterized as [(H(2)O)(0.7)(H(2)O)(4) (eq)(H(2)O)(ax)](2+). The second shell consists in average of 12 water molecules located at a mean distance of 4.4 A. Several other structural parameters such as radial and angular distribution functions and coordination number distributions were analyzed to fully characterize the hydration structure of the TiO(2+) ion in aqueous solution. For the dynamics of the TiO(2+) ion, different sets of dynamical parameters such as Ti=O, Ti-O(eq), and Ti-O(ax) stretching frequencies and ligands' mean residence times were evaluated. During the simulation time of 15 ps, 3 water exchange processes in the first shell were observed at the oxo atom, corresponding to a mean residence time of 3.6 ps. The ligands' mean residence time for the second shell was determined as 3.5 ps. PMID- 17342716 TI - Ultrafast shape recognition to search compound databases for similar molecular shapes. AB - Finding a set of molecules, which closely resemble a given lead molecule, from a database containing potentially billions of chemical structures is an important but daunting problem. Similar molecular shapes are particularly important, given that in biology small organic molecules frequently act by binding into a defined and complex site on a macromolecule. Here, we present a new method for molecular shape comparison, named ultrafast shape recognition (USR), capable of screening billions of compounds for similar shapes using a single computer and without the need of aligning the molecules before testing for similarity. Despite its extremely fast comparison rate, USR will be shown to be highly accurate at describing, and hence comparing, molecular shapes. PMID- 17342717 TI - Molecular dynamics simulation in the grand canonical ensemble. AB - An extended system Hamiltonian is proposed to perform molecular dynamics (MD) simulation in the grand canonical ensemble. The Hamiltonian is similar to the one proposed by Lynch and Pettitt (Lynch and Pettitt, J Chem Phys 1997, 107, 8594), which consists of the kinetic and potential energies for real and fractional particles as well as the kinetic and potential energy terms for material and heat reservoirs interacting with the system. We perform a nonlinear scaling of the potential energy parameters of the fractional particle, as well as its mass to vary the number of particles dynamically. On the basis of the equations of motion derived from this Hamiltonian, an algorithm has been proposed for MD simulation at constant chemical potential. The algorithm has been tested for the ideal gas, for the Lennard-Jones fluid over a wide range of temperatures and densities, and for water. The results for the low-density Lennard-Jones fluid are compared with the predictions from a truncated virial equation of state. In the case of the dense Lennard-Jones fluid and water our predicted results are compared with the results reported using other available methods for the calculation of the chemical potential. The method is also applied to the case of vapor-liquid coexistence point predictions. PMID- 17342718 TI - Structural and electronic properties of boron-doped lithium clusters: ab initio and DFT studies. AB - The lowest-energy structures and electronic properties of the BLi(n) (n = 1-7) clusters are reported using the B3LYP, MP2, and CCSD(T) methods with the aug-cc pVDZ basis set. Though the results at the B3LYP level agree well with those at the CCSD(T) level, the MP2 method is rather unsatisfactory. The first three dimensional ground state in the BLi(n) clusters occurs for BLi(4), and the impurity B atom is seen to be trapped in a Li cage from the BLi(6) cluster onwards. The evolution of the binding energies, vertical ionization potentials, and polarizability with size of cluster shows the BLi(5) cluster to be most stable among the BLi(n) clusters. Besides, the BLi(5) cluster is also found to have the largest reaction enthalpy (49.8 kcal/mol) upon losing a Li atom, which is different from the previous prediction. The unique stability of the 8-valence electron BLi(5) can be understood from the cluster electronic shell model (CSM). However, in contradiction to the prediction of the CSM, the 2s level is filled prior to the 1d level in the BLi(n) clusters. PMID- 17342719 TI - A parallel distributed data CPHF algorithm for analytic Hessians. AB - One of the most commonly used means to characterize potential energy surfaces of reactions and chemical systems is the Hessian calculation, whose analytic evaluation is computationally and memory demanding. A new scalable distributed data analytic Hessian algorithm is presented. Features of the distributed data parallel coupled perturbed Hartree-Fock (CPHF) are (a) columns of density-like and Fock-like matrices are distributed among processors, (b) an efficient static load balancing scheme achieves good work load distribution among the processors, (c) network communication time is minimized, and (d) numerous performance improvements in analytic Hessian steps are made. As a result, the new code has good performance which is demonstrated on large biological systems. PMID- 17342720 TI - Role of binding entropy in the refinement of protein-ligand docking predictions: analysis based on the use of 11 scoring functions. AB - We present results of testing the ability of eleven popular scoring functions to predict native docked positions using a recently developed method (Ruvinsky and Kozintsev, J Comput Chem 2005, 26, 1089) for estimation the entropy contributions of relative motions to protein-ligand binding affinity. The method is based on the integration of the configurational integral over clusters obtained from multiple docked positions. We use a test set of 100 PDB protein-ligand complexes and ensembles of 101 docked positions generated by (Wang et al. J Med Chem 2003, 46, 2287) for each ligand in the test set. To test the suggested method we compared the averaged root-mean square deviations (RMSD) of the top-scored ligand docked positions, accounting and not accounting for entropy contributions, relative to the experimentally determined positions. We demonstrate that the method increases docking accuracy by 10-21% when used in conjunction with the AutoDock scoring function, by 2-25% with G-Score, by 7-41% with D-Score, by 0-8% with LigScore, by 1-6% with PLP, by 0-12% with LUDI, by 2-8% with F-Score, by 7 29% with ChemScore, by 0-9% with X-Score, by 2-19% with PMF, and by 1-7% with DrugScore. We also compared the performance of the suggested method with the method based on ranking by cluster occupancy only. We analyze how the choice of a clustering-RMSD and a low bound of dense clusters impacts on docking accuracy of the scoring methods. We derive optimal intervals of the clustering-RMSD for 11 scoring functions. PMID- 17342721 TI - Characterization of conformational equilibria through Hamiltonian and temperature replica-exchange simulations: assessing entropic and environmental effects. AB - Molecular dynamics simulations based on the replica-exchange framework (REMD) are emerging as a useful tool to characterize the conformational variability that is intrinsic to most chemical and biological systems. In this work, it is shown that a simple extension of the replica-exchange method, known as Hamiltonian REMD, greatly facilitates the characterization of conformational equilibria across large energetic barriers, or in the presence of substantial entropic effects, overcoming some of the difficulties of REMD based on temperature alone. In particular, a comparative assessment of the HREMD and TREMD approaches was made, through computation of the gas-phase free-energy difference between the so-called D(2d) and S(4) states of tetrabutylammonium (TBA), an ionic compound of frequently used in biophysical studies of ion channels. Taking advantage of the greater efficiency of the HREMD scheme, the conformational equilibrium of TBA was characterized in a variety of conditions. Simulation of the gas-phase equilibrium in the 100-300 K range allowed us to compute the entropy difference between these states as well as to describe its temperature dependence. Through HREMD simulations of TBA in a water droplet, the effect of solvation on the conformational equilibrium was determined. Finally, the equilibrium of TBA in the context of a simplified model of the binding cavity of the KcsA potassium channel was simulated, and density maps for D(2d) and S(4) states analogous to those derived from X-ray crystallography were constructed. Overall, this work illustrates the potential of the HREMD approach in the context of computational drug design, ligand-receptor structural prediction and more generally, molecular recognition, where one of the most challenging issues remains to account for conformational flexibility as well for the solvation and entropic effects thereon. PMID- 17342722 TI - Theoretical study of the vertical excited states of benzene, pyrimidine, and pyrazine by the symmetry adapted cluster--configuration interaction method. AB - The ground state and the excited states of benzene, pyrimidine, and pyrazine have been examined by using the symmetry adapted cluster-configuration interaction (SAC-CI) method. Detailed characterizations and the structures of the absorption peaks in the vacuum ultraviolet (VUV), low energy electron impact (LEEI), and electron energy loss (EEL) spectra were theoretically clarified by calculating the excitation energy and the oscillator strength for each excited state. We show that SAC-CI has the power to well reproduce the electronic excitation spectra (VUV, LEEI, and EEL) simultaneously to an accuracy for both the singlet and the triplet excited states originated from the low-lying pi --> pi*, n --> pi*, pi - > sigma* and n --> sigma* excited states of the titled compounds. The present results are compared with those of the previous theoretical studies by methods, such as EOM-CCSD(T), STEOM-CCSD, CASPT2 and TD-B3LYP, etc. PMID- 17342723 TI - Transcriptional profiling of lymphoblast lines from subjects with panic disorder. AB - In attempts to isolate genetic vulnerability factors for panic disorder (PD), a number of investigators have used genome-wide linkage or association analyses. But these attempts have been only modestly successful which suggests that alternative approaches may be needed to define the biology of PD. Therefore, using recently developed genome-wide gene expression profiling, we explored whether transcriptional signatures associated with PD are present in lymphoblast cell line. The expression of 2,469 transcripts in lymphoblast cell lines from 16 subjects was arithmetically increased in every line and significantly increased overall and 354 transcripts was arithmetically decreased in every cell line and significantly decreased overall as compared to those lymphoblast lines from 17 subjects without a history of behavioral illness. Further sex specific analyses showed that in those 10 lines derived from female probands, the expression of a further 67 transcripts was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line and significantly decreased. Conversely, in cell lines from the six male probands, the expression of an additional 212 was arithmetically increased in every line and significantly increased overall and a further 332 transcripts was arithmetically decreased in every cell line. We conclude that lymphoblast cell lines derived from subjects with PD have significant, partially sex dependent changes in gene transcription. Further studies are necessary to correlate these changes in these hemopoetically derived cells with those changes postulated to occur in the CNS in association with PD. PMID- 17342724 TI - Transcriptional profiling of subjects from the Iowa adoption studies. AB - Transcriptional profiling has been used to identify gene expression patterns indicative of general medical illnesses such as atherosclerosis. However, whether these methods can identify common psychiatric disorders has not been established. To answer this question with respect to nicotine use, we used genome-wide expression profiling lymphoblast cell lines from six actively smoking Iowa Adoption Studies (IAS) subjects and nine "clean" control subjects, followed by real-time PCR (RT-PCR) of gene expression patterns in lymphoblast derived RNA from 94 subjects in the IAS. As compared to those from controls without a history of smoking (n = 9), the expression levels of 579 of 29,098 genes were significantly up-regulated and expression levels of 584 of 29,098 genes were significantly down-regulated in lymphoblast lines from currently smoking subjects (n = 6). RT-PCR confirmation of four select RNA levels confirmed the validity of the overall profile and revealed highly significant relationships between the expression of some of these transcripts and (1) major depression, (2) antisocial personality, (3) nicotine dependence, and (4) cannabis dependence. We conclude that the use of expression profiling may contribute significant insights into the biology of complex behavioral disorders. PMID- 17342725 TI - Polo-like kinase 1 may regulate G2/M transition of mouse fertilized eggs by means of inhibiting the phosphorylation of Tyr 15 of Cdc2. AB - Polo-like kinase 1(Plk1) has been reported to be a multifunctional kinase that plays pivotal regulatory roles in microtubule assembly during mammalian early embryonic mitosis. In the present study, we examined the expression of Plk1 at protein and mRNA level in mouse fertilized eggs by Western blot and RT-PCR. We also examined the kinase activity of Plk1. At various developmental phases of mouse one-cell stage embryos, both the protein and the mRNA of Plk1 were uniformly distributed; but the kinase activity of Plk1 increased at G2/M phase and decreased at the end of M phase. At the meantime, the phosphorylation of Tyr 15 of Cdc2 was inhibited at M phase. To investigate its function in mammalian fertilized eggs further, we used specific short hairpin RNAs (shRNA) and scytonemin, the putative inhibitor of Plk1 to suppress the activity of Plk1 in mouse fertilized eggs. Upon blockage of the activation of with Plk1 shRNA and scytonemin in mouse one-cell stage embryos, the cleavage rate decreased and the phosphorylation level of Tyr 15 of Cdc2 increased. These results imply that the Plk1 may regulate cell cycle progression of mouse fertilized eggs by means of inhibiting the phosphorylation of Tyr 15 of Cdc2. PMID- 17342726 TI - Identification and characterization of TSAP, a novel gene specifically expressed in testis during spermatogenesis. AB - Through in silico screens, we have identified many previously uncharacterized genes that display similar expression patterns as the mouse Dazl gene, a germ line-specific marker. Here, we report the identification and characterization of one of these novel genes. TSAP gene encodes a protein with 350 amino acids and contains five ankyrin repeats and a PEST sequence motif. Furthermore, we have generated an anti-TSAP antibody and have used three different approaches (RT-PCR, in situ hybridization, and immunohistochemistry) to investigate the expression profiles of TSAP mRNAs and proteins. TSAP is specifically expressed in testis, but not in other tissues such as ovary. Within the testis, TSAP is detected 10 days after birth and is mainly expressed in spermatocytes (ST) and later stage of germ cells, but not in spermatogonia (SG) or sertoli cells. Therefore, TSAP protein likely plays a role in spermatogenesis. PMID- 17342728 TI - A shared promoter region suggests a common ancestor for the human VCX/Y, SPANX, and CSAG gene families and the murine CYPT family. AB - Many testis-specific genes from the sex chromosomes are subject to rapid evolution, which can make it difficult to identify murine genes in the human genome. The murine CYPT gene family includes 15 members, but orthologs were undetectable in the human genome. However, using refined homology search, sequences corresponding to the shared promoter region of the CYPT family were identified at 39 loci. Most loci were located immediately upstream of genes belonging to the VCX/Y, SPANX, or CSAG gene families. Sequence comparison of the loci revealed a conserved CYPT promoter-like (CPL) element featuring TATA and CCAAT boxes. The expression of members of the three families harboring the CPL resembled the murine expression of the CYPT family, with weak expression in late pachytene spermatocytes and predominant expression in spermatids, but some genes were also weakly expressed in somatic cells and in other germ cell types. The genomic regions harboring the gene families were rich in direct and inverted segmental duplications (SD), which may facilitate gene conversion and rapid evolution. The conserved CPL and the common expression profiles suggest that the human VCX/Y, SPANX, and CSAG2 gene families together with the murine SPANX gene and the CYPT family may share a common ancestor. Finally, we present evidence that VCX/Y and SPANX may be paralogs with a similar protein structure consisting of C terminal acidic repeats of variable lengths. PMID- 17342729 TI - Homologous regulation of estrogen receptor subtypes in goldfish (Carassius auratus). AB - While considerable information is available on the physiological effects of estrogen, much less is known about the regulation of estrogen receptor (ER) subtypes, particularly in non-mammalian vertebrates. Using goldfish as primary experimental model, we investigated sex- and tissue-specific homologous regulation of ER subtypes (ERalpha, ERbetaI, and ERbetaII) by estradiol in vivo, in the liver and gonads. Treatment with estradiol, significantly upregulated transcript levels for all three types of ERs (ERalpha, ERbetaI, and ERbetaII) in the goldfish ovary and testis. In the goldfish liver, treatment with estradiol significantly increased ERalpha, ERbetaI transcript levels without affecting ERbetaII. In all cases increased ER transcript level was correlated with increased ER protein level determined by Western blot analysis, although we are not able to distinguish between ER subtypes. The results provide strong support for the hypothesis that homologous regulation of ERs is tissue- and gender specific, and may be a mechanism for estrogen-mediated regulation of reproduction in goldfish. PMID- 17342727 TI - Concentration and composition of free amino acids and osmolalities of porcine oviductal and uterine fluid and their effects on development of porcine IVF embryos. AB - The concentration of free amino acids and the osmolalities in porcine oviductal (OF) and uterine fluids (UFs) on day 3 (D3) and day 5 (D5) were measured by HPLC and Vapor Pressure Osmometer, respectively. Based on these measurements we designed new media based on PZM3 by modifying the amino acid composition and osmolality. The effectiveness of the modified PZM3 on the development of porcine IVF embryos was then investigated. A total of 24 free amino acids were measured, including 20 protein and 4 nonprotein amino acids (beta-alanine, taurine, ornithine, and citrulline). There was no significant difference in the total concentration of amino acids among D3OF (13.06 +/- 3.63 mmol/L), D3UF (10.54 +/- 5.16 mmol/L), or D5UF (10.23 +/- 6.69 mmol/L). But the total concentration of amino acids in D5OF (5.89 +/- 1.47 mmol/L) was significantly lower than the three fluids above. Some individual amino acids varied significantly depending on where they were collected and from which day. The blastocyst rates of porcine IVF embryos were not improved when embryos were cultured in PZM3 with amino acids at D3OF (PZM3-D3OF, 20.3 +/- 7.9%) or D5UF (PZM3-D5UF, 14.3 +/- 10.7%) concentrations or in PZM3-D3OF for the first 48 (20.5 +/- 15.1), 72 (25.6 +/- 10.4), and 96 (18.7 +/- 10.0) hr and then transferred into PZM3-D5UF compared with PZM3 with Sigma amino acid solution (PZM3-SAA) (30.8 +/- 9.1%). However, when IVF embryos were cultured in PZM3-D5UF, the average nuclear number per blastocyst (57.6 +/- 8.3) was increased compared to PZM3-SAA (40.5 +/- 3.5). The osmolalities in D3OF, D3UF, D5OF, and D5UF were 318 +/- 8, 320 +/- 32, 321, and 293 +/- 8 mOsM, respectively. When the IVF embryos were cultured in PZM3-SAA and PZM3-D3OF at a variety of osmolalities (150-360 mOsM), higher blastocyst rates were obtained at 270-300 mOsM in the PZM3-SAA group (24.6-33.9%) and 270-290 mOsM in PZM3-D3OF group (22.4-24.2%). The blastocyst rate gradually decreased when the osmolality was increased or decreased in both groups. When the embryos were cultured in PZM3-SAA at 330 mOsM for the first 72 hr and then transferred to 250 mOsM (33.3 +/- 3.4%), the blastocyst rate was higher than original PZM3 (21.2 +/- 2.2%) (288 mOsM). PMID- 17342730 TI - Developmental arrest induced in cleavage stage porcine embryos following microinjection of mRNA encoding Brahma (Smarca 2), a chromatin remodeling protein. AB - Smarca 2 (Brahma) and Smarca 4 (Brahma related gene 1, BRG1) alternatively occupy the catalytic site of SWI/SNF chromatin remodeling complexes. Mammalian embryos undergo a dramatic amount of epigenetic remodeling during cleavage development, which plays key roles in regulating both gene transcription and the developmental potential of the embryo. In order to understand how the epigenetic state of cleavage stage embryos is regulated, it is important to identify the factors that mediate epigenetic changes during cleavage development. In this study we hypothesized that altered expression of Smarca 2 would have profound effects on embryo development. The objectives of this study were to determine the expression pattern of Smarca 2 and determine the effects of Smarca 2 overexpression in cleavage stage parthenogenetic porcine embryos. Smarca 2 transcripts are most abundant in germinal vesicle (GV) stage oocytes and decline progressively during cleavage development. At the blastocyst stage, Smarca 2 transcripts are reduced by 18-fold (GV stage oocyte vs. blastocyst stage embryo, P < 0.05). Parthenogenetic porcine embryos injected with mRNA encoding wild type human Smarca 2 exhibited a dramatic developmental arrest as compared to noninjected embryos, embryos injected with GFP mRNA, or mRNA encoding a dominant negative version of human Smarca 2 (P < 0.01). This work demonstrates the importance of Smarca 2 containing SWI/SNF chromatin remodeling complexes in preimplantation porcine embryos and how perturbing the amount of Smarca 2 in porcine embryos disrupts cleavage development. PMID- 17342731 TI - Effects of fetal calf serum, phenazine ethosulfate and either glucose or fructose during in vitro culture of bovine embryos on embryonic development after cryopreservation. AB - This study investigated effects of hexoses, fetal calf serum (FCS), and phenazine ethosulfate (PES) during the culture of bovine embryos on blastocyst development and survival after cryopreservation by slow freezing or vitrification. The basal, control medium was chemically defined (CDM) plus 0.5% fatty acid-free BSA. In vitro-produced bovine zygotes were cultured in CDM-1 with 0.5 mM glucose; after 60 hr, 8-cell embryos were cultured 4.5 days in CDM-2. The 8-cell embryos were randomly allocated to a 2 x 3 x 2 x 3 factorial experimental design with two energy substrates (2 mM glucose or fructose); three additives (0.3 microM PES, 10% FCS, and control); two cryopreservation methods using no animal products (conventional slow freezing or vitrification); and semen from three bulls with two replicates for each bull. A total of 1,107 blastocysts were produced. Fructose resulted in 13% more blastocysts per oocyte than glucose (37.2% vs. 32.9%), and per 8-cell embryo (51.3% vs. 45.3%; P < 0.01). No differences were found for additives (P > 0.1) control, FCS, or PES for blastocysts per oocyte or per 8-cell embryo. There was a significant interaction (P < 0.05) between additives and hexoses for blastocyst production; although trends were similar, the benefit of fructose compared to glucose was greater for controls than for FCS or PES. Culture of embryos with PES, which reduces cytoplasmic lipid content, improved cryotolerance of bovine embryos; post-cryopreservation survival of blastocysts averaged over vitrification and slow freezing (between which there was no difference) was 91.9%, 84.9%, and 60.2% of unfrozen controls (P < 0.01) for PES, control, and FCS groups, respectively. PMID- 17342732 TI - Distribution and expression of phosphorylated histone H3 during porcine oocyte maturation. AB - Phosphorylation modification of core histones is correlated well with diverse chromatin-based cell activities. However, its distribution pattern and primary roles during mammalian oocyte meiosis are still in dispute. In this study, by performing immunofluorescence and Western blotting, spatial distribution and temporal expression of phosphorylated serine 10 or 28 on histone H3 during porcine oocyte meiotic maturation were examined and distinct subcellular distribution patterns between them were presented. Low expression of phosphorylated H3/ser10 was detected in germinal vesicle. Importantly, following gradual dephosphorylation from germinal vesicle (GV) to late germinal vesicle (L GV) stage, a transient phosphorylation at the periphery of condensed chromatin was re-established at early germinal vesicle breakdown (E-GVBD) stage, and then the dramatically increased signals covered whole chromosomes from pre-metaphase I (Pre-MI) to metaphase II (MII). Similarly, hypophosphorylation of serine 28 on histone H3 was also monitored from GV to E-GVBD, indicating dephosphorylation of histone H3 maybe involved in the regulation of meiotic resumption. Moreover, the rim staining on the chromosomes and high levels of H3/ser28 phosphorylation were observed in Pre-MI, MI, and MII stage oocytes. Based on above results, such stage dependent dynamics of phosphorylation of H3/ser 10 and 28 may play specific roles during mammalian oocyte maturation. PMID- 17342733 TI - Expression of a novel T-complex testis expressed 5 (Tctex5) in mouse testis, epididymis, and spermatozoa. AB - Expression of T-complex testis expressed 5 (Tctex5), an orthologue of protein phosphatase-1 inhibitor-3 (PPP1R11), was enhanced in mouse testis and was also expressed in epididymis and spermatozoa. There were three transcripts of Tctex5 including one brain specific and two common transcripts dominant in mouse testis. Tctex5 protein isoforms (75, 52, 32, 25, and 14.3 kDa) were identified. Isoforms of 75 and 52 kDa were spermatogenic-specific and were found in protein fraction containing nuclei, mitochondria, and flagellum accessory, and also in protein fraction containing mainly membranes. Tctex5 was localized in nuclei of pachytene spermatocytes, round spermatocytes, cytoplasm of Sertoli cells in testis; cilia, secretion bodies and nuclei of epithelial cells and interstitium smooth muscle cells in epididymis; and head and principal piece of tail in epididymal spermatozoa. The results suggested that Tctex5 might be a specific protein phosphatase-1 inhibitor in sperm; various Tctex5 transcripts and isoforms and cellular locations imply its different roles in spermatogenesis. Nuclei-type isoforms (75 and 52 kDa) might take part in nucleus remodeling during spermatogenesis whilst membrane-type isoform (52 kDa) might be responsible for dephosphorylation of proteins during capacitation. The other isoforms might play general roles for all kinds of cell types. PMID- 17342734 TI - Time course of meiotic progression after transferring primary spermatocyte into ooplasm at different stages. AB - This study attempted to investigate the time course of meiotic progression after transferring primary spermatocyte (PS) into ooplasm at different maturing stages. In present experiments, PSs were introduced into maturing ooplasts or oocytes by electrofusion. Higher fusion rate was obtained by phytohemagglutinin (PHA) agglutination than by perivitelline space (PVS) insertion. When the ooplasms prepared at 0, 2, 5, and 8.5 hr of in vitro maturation (IVM) were used as recipients and PSs were used as donors, the reconstructed cells extruded the first polar body (PB1) approximately 8.5, 7, 5.5, and 3 hr after electrofusion, respectively. Especially, when ooplasm cultured for 8.5 hr in vitro after GV removal was fused with PS, the PB1 was emitted 7-11 hr after electrofusion. Additionally, the PB1 extrusions of GV and pro-MI oocytes fertilized with PSs were 2.5 hr earlier than control oocytes. The results suggest that (1) PSs undergo the first meiosis in different time courses when introduced into ooplasm at different maturing stages; (2) GV material plays an important role in determining the timing of PB1 extrusion; and (3) first meiotic division of GV and pro-MI oocytes can be accelerated by introducing PS. PMID- 17342735 TI - Dax1 suppresses P450arom expression in medaka ovarian follicles. AB - Dax1 is a member of an unusual orphan nuclear receptor family, and is known to regulate P450arom in mammals and is involved in sex differentiation in some vertebrates. To investigate whether Dax1 is involved in the regulation of the steroidogenic pathway for estrogen biosynthesis in medaka ovarian follicles, we isolated Dax1 cDNA from adult medaka ovaries and analyzed its expression pattern in medaka gonads. In adult ovaries, Dax1 mRNA was detected only in postvitellogenic follicles and was not detected in previtellogenic and vitellogenic follicles. In adult testis, Dax1 mRNA was not detected. We compared the expression pattern of Dax1 with that of Foxl2, Ad4BP/Sf-1, P450c17, and P450arom by in situ hybridization using adjacent sections. In contrast to Dax1 expression, these genes were co-expressed in vitellogenic follicles but were not detected in postvitellogenic follicles. Thus, in medaka ovarian follicles, Dax1 did not show any overlapping expression patterns against Foxl2, Ad4BP/Sf-1, P450c17, and P450arom. Moreover, co-transfection experiments demonstrated that Dax1 inhibits Ad4BP/Sf-1- and Foxl2-mediated P450arom expression. On the other hand, during early sex differentiation, Dax1 mRNA was not detected in both males and females. Our results suggest that Dax1 down-regulates Ad4BP/Sf-1- and Foxl2 mediated P450arom expression in medaka ovarian follicles. PMID- 17342736 TI - Size-selective junctional barrier and Ca(2+)-independent cell adhesion in the testis of Cynops pyrrhogaster: expression and function of occludin. AB - In urodeles which has testicular structure different from that in mammals, blood testis barrier was reported to exist like in mammals. However, molecular and functional analyses of the components of the blood-testis barrier in urodeles have not been reported yet. Toward elucidation of the barrier functions and their molecular components in newt testis, we aimed to isolate occludin cDNAs and obtained two kinds of occludin partial cDNAs (occludin 1 and 2) encoding the putative second extracellular loop. Immunoblot and immunofluorescence studies using antibodies against peptides each corresponding to a part of the second extracellular loop of occludin 1 and 2, and those against beta-catenin and zonula occludens-1 (ZO-1) showed that occludin, as well as beta-catenin and ZO-1, was expressed not only in Sertoli cells but also in germ cells throughout all the stages from spermatogonia to elongate spermatids. Tracer experiments revealed a size-selective barrier which allows small molecules ( approximately 500 Da) to get into cysts through Sertoli cells' barrier, but not larger ones (>1.9 kDa) in the stages from spermatogonia to almost mature sperm. No occludin peptides corresponding to a part of the second extracellular loop destroyed the junctional barrier, while both the peptides and antibodies significantly inhibited reaggregation of the dissociated testicular cells which was to a large extent Ca(2+)-independent. These results indicate that the second extracellular loop of occludin is involved in cell adhesion rather than in size-selective barrier in newt testis, though the possibility cannot be excluded that the peptides were not long enough to inhibit the barrier function. PMID- 17342737 TI - Dynamics of vitellogenin mRNA expression during vitellogenesis in the banana shrimp Penaeus (Fenneropenaeus) merguiensis using real-time PCR. AB - An open reading frame (ORF) of vitellogenin (Vg) cDNA was amplified from the ovaries of the banana shrimp, Penaeus merguiensis. An examination of Vg-deduced amino acid sequence revealed the presence of cleavage sites at a consensus motif for subtilisin-like endoproteases prior to the N-terminal sequences of purified vitellin (Vt) subunits. A comparison of the primary structures of Vg molecules in decapod crustacean species revealed the existence of a common characteristic structure, and phylogenetic analysis reflected the current taxonomic classifications of crustaceans. A PCR product of 1.1 kb encoding the 3'-end of Vg cDNA was cloned from the hepatopancreas. Although its sequence was almost identical to that of the same region of the ovarian Vg, with only 18 nucleotide differences, analysis suggests that they have been subjected to natural selection, indicating that there may be two different, tissue-specific Vg genes in P. merguiensis. This is consistent with the different expression patterns of Vg mRNA, as determined by real-time PCR. Vg mRNA levels were maintained at low levels during the previtellogenic stage and they increased as vitellogenesis progressed to reach a peak at the early vitellogenic stage in the ovary or at the vitellogenic stage in the hepatopancreas, and thereafter, levels decreased. Expression of Vg mRNA was much higher in the ovary compared to the hepatopancreas at all stages of ovarian development, implying that the ovary is mainly responsible for Vt synthesis. These indicate that penaeids constitute a unique model for vitellogenesis, showing intraovarian gene expression and synthesis of yolk protein. PMID- 17342738 TI - Selenium improves the developmental ability and reduces the apoptosis in porcine parthenotes. AB - Selenium is an essential trace element in conventional tissue culture media to guarantee adequate biosynthesis of selenoprotein in cellular antioxidant system to protect the cells from oxidative damage and apoptosis. This study investigated the effect of selenium, in the form of sodium selenite (SS), on developmental ability and quality of in vitro produced porcine parthenotes. For this, parthenogenetic presumptive diploid zygotes were produced by electroactivation and cultured in the absence or presence of SS at different concentrations (0, 2.5, 25, 250 ng/ml) in a serum-free defined culture medium supplemented with polyvinyl alcohol (PVA) or bovine serum albumin (BSA). Results showed that, development rate of 2-4 cell stage parthenotes to blastocyst and their cell number was increased while TUNEL index was decreased, in a dose-dependent manner, when SS was supplemented to NCSU23 + PVA. Interestingly, the blastocyst rate and their quality approached to those cultured in NCSU23 + BSA (P < 0.05), thereby suggesting PVA + 25 ng/ml SS to be a partial replacement of BSA. In the presence of PVA, supplementation of SS at a concentration of 25 ng/ml did not improve the cleavage rate of in vitro matured oocytes but there was significant improvement in the blastocyst rate (45.4 +/- 8.8% vs. 12.7 +/- 4.8%), total nuclei number (42.1 +/- 3.5 vs. 31.3 +/- 2.9) and inner cell mass (ICM) rate (29.4 +/- 1.5% vs. 21.3 +/- 1.2%) and decrease in TUNEL index (5.6 +/- 0.5 vs. 12.9 +/- 1.3) compared to nonsupplemented controls. The SS supplementation also decreased the BAX:BCL-xL transcript ratio, increased the expression of ERK1/2 and glutathione peroxidase (GPX) and reduced the level of Caspase 3 proteins (P < 0.05). These data thus suggest that SS improves the development rate and quality of porcine parthenotes by preventing oxidative damage and apoptosis. PMID- 17342739 TI - Apoptotic effects of a progesterone receptor antagonist on rat granulosa cells are not mediated via reduced protein isoprenylation. AB - Progesterone is a survival factor in rat periovulatory granulosa cells. The mechanisms involved are unclear but progesterone receptor (PGR) antagonists have been shown to inhibit cholesterol synthesis and induce apoptosis. Furthermore, reports suggest that statins induce apoptosis by inhibition of protein isoprenylation. Statins inhibit the rate-limiting step of the cholesterol synthesis, thereby reducing availability of intermediates used for the post translational isoprenylation process. It has been suggested that PGR antagonists in a similar manner induce apoptosis by decreasing cholesterol synthesis and thereby protein isoprenylation. In this study we hypothesized that the mechanism by which the nuclear PGR antagonist Org 31,710 induces apoptosis in rat periovulatory granulosa cells, is by decreasing cholesterol synthesis and thereby general cell protein isoprenylation. Incubation of isolated granulosa cells with Org 31,710 or simvastatin for 22 hr resulted in increased apoptosis and reduced cholesterol synthesis. However, simvastatin caused a substantial inhibition of cholesterol synthesis after 6 hr in culture without inducing apoptosis. In contrast, Org 31,710 had only a modest effect on cholesterol synthesis after 6 hr while it significantly induced apoptosis. Addition of isoprenylation substrates partially reversed apoptosis induced by simvastatin and to a lesser extent apoptosis induced by Org 31,710. In addition, and in contrast to Org 31,710, simvastatin caused a decrease in isoprenylation of a selected isoprenylation marker protein, the Ras-related protein RAB11. In conclusion, we demonstrate that the PGR antagonist inhibits cholesterol synthesis in granulosa cells but reduced protein isoprenylation is not the mediating mechanism of increased apoptosis as previously hypothesized. PMID- 17342740 TI - The quiet embryo hypothesis: molecular characteristics favoring viability. AB - It has been proposed that the viability of early mammalian embryos is associated with a metabolism that is "quiet" rather than "active" (Leese HJ, 2002:BioEssays 24:845-849). The data on which this hypothesis was based were largely drawn from measurements on the depletion and appearance of amino acids from the culture medium. Data on the de novo synthesis of protein in in vivo- and in vitro-derived bovine embryos, as determined from the flux of radiolabeled methionine, have provided further support of the hypothesis and are interpreted to provide a new set of testable propositions that could illuminate the molecular basis of the quiet metabolism phenotype. The propositions are based on the premise that the extent of DNA damage, and the RNA and protein content of the immature oocyte, are key factors in determining whether the zygote progresses to the blastocyst stage. We propose that stochastic events and environmental stresses determine whether the condition of the genome, transcriptome, and proteome of the zygote will support development. Several molecular components are identified that may determine the viability of a zygote, and we speculate that the cellular response to unfavorable events or excessive DNA damage may be the premature activation of the embryonic genome and of apoptosis. PMID- 17342741 TI - p19Ink4d and p18Ink4c cyclin-dependent kinase inhibitors in the male reproductive axis. AB - The loss of the cyclin-dependent kinase inhibitors (CKIs) p18(Ink4c) and p19(Ink4d) leads to male reproductive defects (Franklin et al., 1998. Genes Dev 12: 2899-2911; Zindy et al., 2000. Mol Cell Biol 20: 372-378; Zindy et al., 2001. Mol Cell Biol 21: 3244-3255). In order to assess whether these inhibitors directly or indirectly affect male germ cell differentiation, we examined the expression of p18(Ink4c) and p19(Ink4d) in spermatogenic and supporting cells in the testis and in pituitary gonadotropes. Both p18(Ink4c) and p19(Ink4d) are most abundant in the testis after 18 days of age and are expressed in purified populations of spermatogenic and testicular somatic cells. Different p18(Ink4c) mRNAs are expressed in isolated spermatogenic and Leydig cells. Spermatogenic cells also express a novel p19(Ink4d) transcript that is distinct from the smaller transcript expressed in Sertoli cells, Leydig cells and in other tissues. Immunohistochemistry detected significant levels of p19(Ink4d) in preleptotene spermatocytes, pachytene spermatocytes, condensing spermatids, and Sertoli cells. Immunoprecipitation-Western analysis detected both CKI proteins in isolated pachytene spermatocytes and round spermatids. CDK4/6-CKI complexes were detected in germ cells by co-immunoprecipitation, although the composition differed by cell type. p19(Ink4d) was also identified in FSH+ gonadotrophs, suggesting that this CKI may be independently required in the pituitary. Possible cell autonomous and paracrine mechanisms for the spermatogenic defects in mice lacking p18(Ink4c) or p19(Ink4d) are supported by expression of these CKIs in spermatogenic cells and in somatic cells of the testis and pituitary. PMID- 17342742 TI - Effects of either glucose or fructose and metabolic regulators on bovine embryo development and lipid accumulation in vitro. AB - Our objective was to determine if replacing glucose with fructose would decrease cytoplasmic lipid accumulation during culture of embryos with or without regulators of metabolism. In vitro-produced bovine zygotes were cultured 60 hr in chemically defined medium-1 (CDM-1) plus 0.5% BSA and 0.5 mM fructose or glucose in Experiment 1, and glucose in Experiment 2. In both experiments, 8-cell embryos were next cultured 135 hr in CDM-2 plus 2 mM fructose or glucose in factorial combination with five treatments: (Experiment 1: control, 10% fetal calf serum (FCS), 0.3 microM phenazine ethosulfate (PES), 30 microM dinitrophenol (DNP), and PES + DNP), and (Experiment 2: control, PES, PES + DNP, and 1 and 3 microg/ml cerulenin (C1 and C3)). Day 7.5 blastocysts were stained with Sudan Black B to quantify cytoplasmic lipid droplets as small (SD, <2 microm), medium (MD, 2-6 microm), or large (LD, >6 microm). Blastocyst rates per oocyte were 22% (Experiment 1) and 15% (Experiment 2) higher (P < 0.05) for fructose than glucose. For Experiment 1, numbers of MD were lower for PES, DNP, and PES + DNP than control and FCS (P < 0.05). LD were lower for PES and DNP than control, and higher for FCS than all other treatments (P < 0.05). For Experiment 2, MD were lower (P < 0.05) for PES, and PES + DNP than C1, C3, and control. For LD, PES was lower (P < 0.05) than control, C1, and C3, but not different from PES + DNP. The only effect of hexose on lipids was that fructose resulted in fewer MD (P < 0.01) in Experiment 2. In conclusion, fructose produced more blastocysts than glucose, and PES reduced lipid accumulation. PMID- 17342743 TI - Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mouse prostate model (TRAMP). AB - BACKGROUND: Several of the proposed mechanisms for the actions of the liposterolic extract of saw palmetto (SPE) are exerted on known risk factors for prostate cancer (CaP). This study investigated whether SPE could prevent the progression of CaP in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model. METHODS: Two different doses of SPE designed to deliver 50 mg/kg/day SPE and 300 mg/kg/day SPE were administered in a custom diet to TRAMP mice for 12 or 24 weeks. Body and organ weights were used to evaluate toxicity, and radioimmunoassay was used to measure plasma and tissue androgen levels to monitor effects of SPE on 5alpha reductase activity. Prostate tissues were evaluated histologically to determine the effect of treatment on tumor grade, cell proliferation, and apoptosis. RESULTS: Treatment with 300 mg/kg/day SPE from 4 to 24 weeks of age significantly reduced the concentration of 5alpha dihydrotestosterone (DHT) in the prostate and resulted in a significant increase in apoptosis and significant decrease in pathological tumor grade and frank tumor incidence. CONCLUSIONS: Dietary supplementation with SPE may be effective in controlling CaP tumorigenesis. SPE suppression of prostatic DHT levels lends support to the hypothesis that inhibition of the enzyme 5alpha-reductase is a mechanism of action of this substance. PMID- 17342744 TI - HSP27 and HSP70 interact with CD10 in C4-2 prostate cancer cells. AB - BACKGROUND: CD10 is an approximately 100 kDa transmembrane metallo-endopeptidase. CD10 is strongly expressed by normal prostate epithelium. While only 30% of primary prostate tumors express CD10, it is strongly expressed by most lymph node metastases. The function of CD10 and the interaction between CD10 and other cellular proteins in prostate cancer (CaP) is not well defined. Cellular context may ultimately determine its biologic function in CaP. In this study, we compared CD10 mRNA and protein expression between benign and malignant prostate cells and employed proteomic analysis to identify proteins that interact with CD10 in C4-2 prostate cancer cells. METHODS: CD10 mRNA and protein expression was compared using RT-PCR and Western blotting. CD10-protein complexes were isolated by immunoprecipitation using anti-CD10 monoclonal antibodies. Eluted fractions were combined, trypsinized, and the resulting peptides analyzed by microLC-ESI-MS/MS. The parent proteins were identified by searching MS/MS spectra against a human protein database using SEQUEST. RESULTS: There were no differences in CD10 mRNA length or CD10 protein molecular weight between normal tissue and CaP. We identified 75 proteins unique to or heavily enriched in the CD10 immunoprecipitates by proteomic analysis. The 27 kDa heat shock protein (HSP27) and HSP70 were identified in three separate precipitations. Protein identification by proteomics was confirmed by Western blotting. Protein complexes immunopurified from C4-2 protein extracts using anti-HSP27 and anti-HSP70 antibodies were found to contain CD10. CONCLUSIONS: The function of CD10 in prostate cancer is largely unknown. In the C4-2 CaP cell line, CD10 was found to interact with both HSP27 and HSP70. PMID- 17342745 TI - Frequency and number of neuroendocrine tumor cells in prostate cancer: no difference between radical prostatectomy specimens from patients with and without neoadjuvant hormonal therapy. AB - BACKGROUND: Neuroendocrine tumor cells in prostate cancer are thought to increase after hormonal therapy due to neuroendocrine differentiation of tumor cells. This assumption is based on the histological analyses of limited portions of the cancerous lesions examined. METHODS: Radical prostatectomy specimens were obtained from 122 consecutive patients with prostate adenocarcinoma, 70 of whom underwent prostatectomy alone (Group A) and 52 with neoadjuvant hormonal therapy (Group B). Sections from all the 5-mm-thick slices from formalin-fixed specimens were immunostained for chromogranin-A, and the total number of choromogranin-A positive neuroendocrine tumor cells were counted. RESULTS: No difference was found between Groups A and B in the frequency of cancer with neuroendocrine cells. The total number of neuroendocrine cells in cancer varied widely with no difference of median values in the two groups. CONCLUSIONS: These results do not support the assumption that hormonal therapy induces neuroendocrine differentiation, but suggest androgen-independent neuroendocrine cells existed before therapy. PMID- 17342746 TI - External beam radiotherapy (EBRT) suppressed prostate stem cell antigen (PSCA) mRNA expression in clinically localized prostate cancer. AB - BACKGROUND: Prostate stem cell antigen (PSCA), a recently identified glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the Thy-1/Ly-6 family of cell surface antigens, is overexpressed in human prostate cancer (PCa). Our recent data indicated that complete androgen ablation could significantly suppress PSCA mRNA expression in primarily organ-confined PCa. The effect of external beam radiotherapy (EBRT), one of the curative treatment options for localized PCa, on tumor PSCA mRNA expression has not been elucidated. The purpose of the present study was to investigate the variations in the expression levels of PSCA mRNA before and after EBRT, and further evaluate the prognostic value of PSCA in this disease. MATERIALS AND METHODS: Between January 1999 and June 2005, 87 men with clinically localized adenocarcinoma of the prostate received only EBRT with a total dose of 65-70 Gy for 6.5-7 weeks. PSCA in situ hybridization (ISH) was performed on the cancerous pretreatment biopsy or transurethral resection of prostate (TURP) tissue and post-treatment biopsy tissue of all 87 men, respectively. Tumor cytoplasmic staining of PSCA mRNA was evaluated by two independent pathologists and the differences of PSCA mRNA expression levels between the samples before and after EBRT were analyzed using the Student's t-test. Twenty-four to seventy months continuous follow-up studies after treatment were performed and aimed at assessing the correlation of PSCA mRNA expression level with biochemical relapse and/or distant metastases from the cancer. RESULTS: The percent of cells positive for PSCA mRNA by ISH labeling declined from 71.2% (0-93%) +/- 9.7% before EBRT to 30.7% (0-90%) +/- 5.3% after EBRT (P<0.001). Before EBRT, 81 of 87 cases (93.1%) were positive for PSCA mRNA labeling, however, after EBRT the percentage of positive reactivity of PSCA mRNA was decreased to 62 of 81 cases (76.5%), in which 59 men (95.2%) were found without biochemical relapse or distant metastases on follow-up. This decline in PSCA mRNA labeling was directly proportional to higher pretreatment serum PSA level, higher tumor grade (Gleason score), and higher clinical T stage. The rest 19 cases had the increased percentage of cells positive for PSCA mRNA after EBRT, in which 15 cases developed biochemical relapse and/or distant metastases from tumor on follow-up. CONCLUSIONS: We found that EBRT for PCa can significantly suppress PSCA mRNA expression and the elevated PSCA mRNA level after EBRT may be a clinically adverse predictor for tumor progression. PMID- 17342747 TI - Sonic and desert hedgehog signaling in human fetal prostate development. AB - BACKGROUND: Hedgehog signaling is thought to play an important role in rodent prostate organogenesis and morphogenesis. However, the role of this signaling pathway in human fetal prostate development has not been investigated. METHODS: Twenty-five human fetal prostates at various developmental stages (10-39 weeks) were included. Fifteen specimens were processed for H&E and immunohistochemical staining of the Hedgehog signaling components: Sonic Hedgehog (SHH), Desert Hedgehog (DHH), Patched-1(PTC1), Patched-2 (PTC2), Smoothened (SMO), GLI1, and proliferating cell nuclear antigen (PCNA). SHH, DHH, and GLI1 expression was also analyzed in ten snap-frozen specimens by Western blot. RESULTS: SHH, DHH, SMO, PTC1, GLI1, and PCNA expression, assessed by a semi-quantitative immunohistochemical method, was found mainly in the developing prostatic epithelial ducts, beginning at 10 weeks and peaking at 16 and 28 weeks with a dip occurring at 20 weeks, with the exception of PTC2. CONCLUSION: Both SHH and DHH signaling components were detected during human fetal prostate development. Despite the high expression of PTC2 in the epithelium as well as the stroma in the early time of development, the expression of SHH, DHH, SMO, PTC1, and a SHH/DHH target transcription factor, GLI-1, were all largely restricted to epithelium in the developing prostate, suggesting that SHH/DHH signaling is primarily through an autocrine mechanism in human fetal prostate organogenesis. PMID- 17342748 TI - Non-steroidal antiandrogens act as AF-1 agonists under conditions of high androgen-receptor expression. AB - BACKGROUND: The mechanism of resistance acquisition to antiandrogens in prostate cancer is not fully understood. Numerous clinical and basic research studies have shown expression of androgen receptors (ARs) increases in hormone-refractory prostate cancer and therefore we explored possible molecular mechanisms by which prostate cancer acquires resistance to antiandrogens under conditions of increased AR expression. METHODS: In order to study resistance to antiandrogens at the AR transactivation level we used a human AR (hAR) reporter assay system. In addition, we utilized an hAR deletion mutant to determine the functional domain responsible for the acquisition of resistance. RESULTS: Increased hAR protein expression enhanced the sensitivity of AR transactivation to low concentrations of DHT, and also reduced the inhibitory activity of the non steroidal antiandrogens, hydroxyflutamide, and bicalutamide on DHT-induced AR transactivation. Moreover, these antiandrogens acquired agonistic activity under conditions of high hAR protein expression. Such agonistic activity of antiandrogens was not detected in an hAR deletion mutant (hAR-DeltaA/B) that lacked an A/B domain with AF-1 activity. CONCLUSIONS: We found that non-steroidal antiandrogens act as AF-1 agonists under conditions of high AR protein expression. This partial antagonistic property of antiandrogens may be a molecular mechanism by which prostate cancer develops resistance to these drugs. PMID- 17342749 TI - Reactive oxygen species mediate androgen receptor- and serum starvation-elicited downstream signaling of ADAM9 expression in human prostate cancer cells. AB - BACKGROUND: The A Disintegrin And Metalloprotease (ADAM) family is a group of transmembrane proteins containing cell adhesive and proteolytic functional domains. ADAM9 expression was shown to be mediated by androgen receptor (AR) and stress conditions. This study determined a common mediator responsible for ADAM9 protein regulation which supports human prostate cancer (PCa) cell growth and survival. METHODS: ADAM9 protein expression was measured under androgen, anti androgen, hydrogen peroxide, and/or serum starvation conditions in PCa cells. The roles of reactive oxygen species (ROS) were assessed in the presence or absence of recombinant catalase, or in cells stably transfected with either catalase- or a control neo-cDNA expression vector. ROS was assayed by dihydroethidium (DHE) followed by FACS analysis. RESULTS: ADAM9 protein expression was upregulated by androgen in AR-positive but not in AR-negative PCa cells. The anti-androgen bicalutamide effectively blocked this induction. While serum starvation enhanced ADAM9 expression in AR-positive PCa cells, this stress condition did not alter ADAM9 expression in AR-negative PCa cells. Parallel results also showed that androgen treatment or serum starvation enhanced ROS only in AR-positive but not in AR-negative PCa cells. ROS appears to be a common downstream mediator of androgen- or serum starvation-induced ADAM9 expression since addition of hydrogen peroxide or introduction of catalase, either enhanced or abolished respectively ADAM9 protein expression by both AR-positive and -negative PCa cells. CONCLUSIONS: These findings suggest that ROS is: a common mediator responsible for ADAM9 protein induction in human PCa cells, downstream from AR, and stress response signaling. PMID- 17342750 TI - DNA copy number alterations in prostate cancers: a combined analysis of published CGH studies. AB - BACKGROUND: Identifying genomic regions that are commonly deleted or gained in neoplastic cells is an important approach to identify tumor suppressor genes and oncogenes. Studies in the last two decades have identified a number of common DNA copy number alterations in prostate cancer. However, because of various sample sizes, diverse tumor types and sources, as well as a variety of detection methods with various sensitivities and resolutions, it is difficult to summarize and fully interpret the overall results. METHODS: We performed a combined analysis of all published comparative genomic hybridization (CGH) studies of prostate cancer and estimated the frequency of alterations across the genome for all tumors, as well as in advanced and localized tumors separately. A total of 41 studies examining 872 cancers were included in this study. RESULTS: The frequency of deletions and gains were estimated in all tumors, as well as in advanced and localized tumors. Eight deleted and five gained regions were found in more than 10% of the prostate tumors. An additional six regions were commonly deleted and seven were commonly gained in advanced tumors. While 8p was the most common location of deletion, occurring in about a third of all tumors and about half of advanced tumors, 8q was the most commonly gained region, affecting about a quarter of all tumors and about half of all advanced tumors. CONCLUSIONS: The large number of tumors examined in this combined analysis provides better estimates of the frequency of specific alterations in the prostate cancer cell genome, and offers important clues for prioritizing efforts to identify tumor suppressor genes and oncogenes in these altered regions. PMID- 17342751 TI - RASSF1A promoter methylation is frequently detected in both pre-malignant and non malignant microdissected prostatic epithelial tissues. AB - BACKGROUND: The RASSF1A gene is a tumor suppressor gene inactivated by hypermethylation in a very wide variety of malignant tumors including prostate cancer. METHODS: In this study we have used laser capture microdissection to provide pure cell populations to investigate the methylation status of 16 CpG sites in the promoter region of this gene in prostatic intra-epithelial neoplasia, in histologically normal epithelial cells associated with these lesions and in epithelial cells from benign prostatic hyperplasia. RESULTS: Unexpectedly, frequent methylation, detected by sequence analysis following bisulphite treatment, was observed in benign epithelium as well as in the lesions associated with prostatic intra-epithelial neoplasia and at high risk of cancer formation. Fifty percent or more CpG sites were methylated in 7/14 prostatic intra-epithelial neoplasms, 8/11 histologically normal epithelial cells and 8/12 specimens of benign prostatic tissue. CONCLUSION: These observations suggest that methylation of the RASSF1A gene is present in both pre-malignant and benign epithelia and suggests quantitation is required for it to be an effective marker of early prostate cancer. PMID- 17342752 TI - Non-invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model. AB - BACKGROUND: We previously established a bioluminescent transgenic mouse model, sPSA-Luc, with luciferase gene expression restricted to the prostate under the control of the supra prostate-specific antigen (sPSA) promoter. We now assess the feasibility of generating bigenic mice, TRAMP-Luc, with the sPSA-Luc as the founder strain crossbred with TRAMP (transgenic adenocarcinoma mouse prostate) mice, to evaluate non-invasively the metastatic potential of prostate tumors. METHODS: TRAMP-Luc mice were obtained as [C57BL/6 TRAMP x FVB sPSA-Luc] F1 offspring. Tumor development in 10 TRAMP-Luc males was followed by bioluminescence imaging from 8 to 24 weeks of age. Immunohistochemical (IHC) staining for T antigen (Tg), androgen receptor (AR), luciferase and/or pathological analysis verified the tumor distribution in the imaged tissues including prostate gland, lymph node and bone. RESULTS: Group I animals that presented with no grossly visible tumors showed prostate-confined bioluminescence with slightly increased signal intensity with age. Group II animals that developed large tumors displayed a widely distributed and biphasic bioluminescence pattern. The peak was reached between 10 and 14 weeks of age, then markedly decreased or even disappeared beyond week 16, except for one mouse that showed an increased bioluminescence signal at the jaw bone and hind limbs at week 22. These tumors were shown by IHC to contain Tg but lost AR and luciferase beyond week 16 in poorly differentiated prostate tumors. CONCLUSION: A direct correlation between bioluminescence emission and AR expression was found in TRAMP Luc tumor progression model. This model allows non-invasive imaging of prostate cancer metastases to bone and soft tissues. PMID- 17342753 TI - IRL-1620, a tumor selective vasodilator, augments the uptake and efficacy of chemotherapeutic agents in prostate tumor rats. AB - BACKGROUND: IRL-1620, a potent endothelin B receptor agonist, enhanced the efficacy of paclitaxel in a breast tumor model, but its effect in prostate cancer is not known. The present study was conducted to evaluate the effect of IRL-1620 on tumor perfusion, uptake of [(14)C]-doxorubicin in the tumor and efficacy of doxorubicin (DOX), and 5-flurouracil (5-FU) in a rat prostate tumor model. METHODS: JHU-4 (Mat-Lu) cells inoculated prostate tumor model in Copenhagen rats was used for the study. RESULTS: Administration of IRL-1620 (3 nmol/kg, i.v) significantly increased (102.8%) prostate tumor perfusion and tumor uptake of [(14)C]-doxorubicin (115%) compared to vehicle treated rats. Results of the efficacy study demonstrate that IRL-1620 administration 15 min prior to DOX (5 mg/kg) or 5-FU (50 mg/kg) on every third day for a total of four doses significantly reduced tumor volume compared to vehicle treated rats. CONCLUSIONS: IRL-1620 significantly enhanced the uptake and efficacy of anticancer agents in prostate cancer. PMID- 17342754 TI - Parametric survival analysis and taxonomy of hazard functions for the generalized gamma distribution. AB - The widely used Cox proportional hazards regression model for the analysis of censored survival data has limited utility when either hazard functions themselves are of primary interest, or when relative times instead of relative hazards are the relevant measures of association. Parametric regression models are an attractive option in situations such as this, although the choice of a particular model from the available families of distributions can be problematic. The generalized gamma (GG) distribution is an extensive family that contains nearly all of the most commonly used distributions, including the exponential, Weibull, log normal and gamma. More importantly, the GG family includes all four of the most common types of hazard function: monotonically increasing and decreasing, as well as bathtub and arc-shaped hazards. We present here a taxonomy of the hazard functions of the GG family, which includes various special distributions and allows depiction of effects of exposures on hazard functions. We applied the proposed taxonomy to study survival after a diagnosis of clinical AIDS during different eras of HIV therapy, where proportionality of hazard functions was clearly not fulfilled and flexibility in estimating hazards with very different shapes was needed. Comparisons of survival after AIDS in different eras of therapy are presented in terms of both relative times and relative hazards. Standard errors for these and other derived quantities are computed using the delta method and checked using the bootstrap. Description of standard statistical software (Stata, SAS and S-Plus) for the computations is included and available at http://statepi.jhsph.edu/software. PMID- 17342755 TI - Germline transgenesis and insertional mutagenesis in the ascidian Ciona intestinalis. AB - Stable transgenesis is a splendid technique that is applicable to the creation of useful marker lines, enhancer/gene traps, and insertional mutagenesis. Recently, transposon-mediated transformation using a Tc1/mariner transposable element Minos has been reported in two ascidians: Ciona intestinalis and C. savignyi. The transposon derived from an insect, Drosophila hydei, has high activity for excision in Ciona embryos and transposition in their genome. As much as 37% of Minos-injected C. intestinalis transmitted transposon insertions to the subsequent generation. Minos-mediated germline transgenesis has also been achieved by means of electroporation method. Minos techniques have been applied to enhancer traps and insertional mutagenesis in Ciona. For those reasons, Minos offers the high potential for use as a powerful tool for future genetic studies. This review specifically addresses recent achievements of transformation techniques in Ciona, as exemplified using the Minos system. PMID- 17342756 TI - Kidney development and gene expression in the HIF2alpha knockout mouse. AB - The hypoxia-inducible transcription factor-2 (HIF2), a heterodimer composed of HIF2alpha and HIF1beta subunits, drives expression of genes essential for vascularization, including vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2, Flk-1). Here, we used a HIF2alpha/LacZ transgenic mouse to define patterns of HIF2alpha transcription during kidney development and maturation. Our results from embryonic heterozygotes showed HIF2alpha/LacZ expression by apparently all renal endothelial cells. At 4 weeks of age, glomerular mesangial and vascular smooth muscle cells were also positive together with endothelial cells. These expression patterns were confirmed by electron microscopy using Bluo-gal as a beta-galactosidase substrate. Small numbers of glomerular and tubular epithelial cells were also positive at all stages examined. Light and electron microscopic examination of kidneys from HIF2alpha null embryos showed no defects in renal vascular development or nephrogenesis. Similarly, the same amounts of Flk-1 protein were seen on Western blots of kidney extracts from homozygous and heterozygous HIF2alpha mutants. To examine responsiveness of HIF2alpha null kidneys to hypoxia, embryonic day 13.5 metanephroi were cultured in room air or in mild (5% O(2)) hypoxia. For both heterozygous and null samples, VEGF mRNA levels doubled when metanephroi were cultured in mild hypoxia. Anterior chamber grafts of embryonic HIF2alpha knockouts were morphologically indistinguishable from heterozygous grafts. Endothelial markers, platelet endothelial cell adhesion molecule and BsLB4, as well as glomerular epithelial markers, GLEPP1 and WT-1, were all expressed appropriately. Finally, we undertook quantitative real-time polymerase chain reaction of kidneys from HIF2alpha null embryos and wild-type siblings and found no compensatory up-regulation of HIF1alpha or -3alpha. Our results show that, although HIF2alpha was widely transcribed by kidney endothelium and vascular smooth muscle, knockouts displayed no detectable deficits in vessel development or VEGF or Flk-1 expression. PMID- 17342757 TI - Spinal cord dopamine receptor expression and function in mice with 6-OHDA lesion of the A11 nucleus and dietary iron deprivation. AB - It is suggested that dysfunction of the diencephalospinal dopaminergic (DAergic) pathway may cause restless legs syndrome. We examined the mRNA and protein levels as well as DA receptor subtypes function within the lumbar spinal cord of an RLS animal model. C57BL/6 male mice with or without iron deprivation were lesioned with 6-hydroxydopamine (6-OHDA) in the bilateral A11 nuclei. Locomotor behaviors were observed. DA concentration, mRNA, and protein levels of D1, D2, and D3 receptors in the lumbar spinal cords were analyzed, and the specific binding of D1, D2, and D3 receptors was determined using [(3)H]SCH23390, [(3)H]Spiperone, and [(3)H]PD128907 radioligands respectively. The behavioral tests showed that the locomotor activities were increased significantly in the mice treated with iron-deficiency (ID) diet and 6-OHDA lesions, which were reversed by the D2/D3 agonist ropinirole. DA in the spinal cord was decreased significantly by 6-OHDA lesioning in A11. D2/D3 mRNA and protein levels as well as their binding capacity in the spinal cord were decreased significantly by 6-OHDA lesions. ID with 6-OHDA lesions produced a synergistic greater decrease of D2 binding. Although ID increased D1 mRNA and protein expression in the spinal cord, it did not significantly change D1 receptor binding. The present study suggests that ID and 6-OHDA lesions in A11 nuclei differentially altered the D1, D2, and D3 receptors expression and binding capacity in the lumbar spinal cord of RLS animal model, which was accompanied by changes in locomotor activities. PMID- 17342758 TI - Spontaneous lesions in the reproductive tract and mammary gland of female non human primates. AB - Because of their close phylogenic relationship with humans, the use of non-human primates (NHP) as experimental subjects has a long history in biomedical research. Although research topics have shifted focus and species used have changed, NHP remain vital as models in basic and applied research. While there is a wealth of information available on the spontaneous lesions of NHP, most of this information is fragmented, dated, or narrow in focus, often limited to single case reports. This review attempts to integrate this information to illustrate and enumerate the spectrum of spontaneous pathology of the reproductive tract and mammary gland of NHP. Although not the focus of this review, steroid-related changes are inextricably linked to these tissues, and brief consideration is given to this subject as well. PMID- 17342761 TI - Rearrangement of microtubule polarity orientation during conversion of dendrites to axons in cultured pyramidal neurons. AB - Axons and dendrites of neurons differ in the polarity orientation of their microtubules. Whereas the polarity orientation of microtubules in axons is uniform, with all plus ends distal, that in dendrites is nonuniform. The mechanisms responsible for establishment and maintenance of microtubule polarity orientation in neuronal processes remain unclear, however. We previously described a culture system in which dendrites of rat cortical neurons convert to axons. In the present study, we examined changes in microtubule polarity orientation in such dendrites. With the use of the hooking procedure and electron microscopy, we found that microtubule polarity orientation changed from nonuniform to uniform, with a plus end-distal arrangement, in dendrites that gave rise to axons during culture of neurons for 24 h. Microtubule polarity orientation remained nonuniform in dendrites that did not elongate. Axon regeneration at the dendritic tip thus triggered the disappearance of minus end distal microtubules from dendrites. These minus end-distal microtubules also disappeared from dendrites during axon regeneration in the presence of inhibitors of actin polymerization, suggesting that actin-dependent transport of microtubules is not required for this process and implicating a previously unidentified mechanism in the establishment and maintenance of microtubule polarity orientation in neuronal processes. PMID- 17342762 TI - Rho plays a central role in regulating local cell-matrix mechanical interactions in 3D culture. AB - The purpose of this study was to assess quantitatively the role of the small GTPase Rho on cell morphology, f-actin organization, and cell-induced matrix remodeling in 3D culture. Human corneal fibroblasts (HTK) were infected with adenoviruses that express green fluorescent protein (GFP) or GFP-N19Rho (dominant negative Rho). One day later cells were plated inside collagen matrices and allowed to spread for 24 h. Cells were fixed and stained for f-actin. Fluorescent (for f-actin) and reflected light (for collagen fibrils) images were acquired using confocal microscopy. Fourier transform analysis was used to assess local collagen fibril alignment, and changes in cell morphology and collagen density were measured using MetaMorph. The decrease in matrix height was used as an indicator of global matrix contraction. HTK and HTK-GFP cells induced significant global matrix contraction; this was inhibited by N19Rho. HTK and HTK-GFP fibroblasts generally had a bipolar morphology and occasional intracellular stress fibers. Collagen fibrils were compacted and aligned parallel to stress fibers and pseudopodia. In contrast, HTK-GFPN19 cells were elongated, and had a more cortical f-actin distribution. Numerous small extensions were also observed along the cell body. In addition, both local collagen fibril density and alignment were significantly reduced. Rho plays a key role in regulating both the morphology and mechanical behavior of corneal fibroblasts in 3D culture. Overall, the data suggest that Rho-kinase dependent cell contractility contributes to global and local matrix remodeling, whereas Rho dependent activation of mDia and/or other downstream effectors regulates the structure and number of cell processes. PMID- 17342763 TI - Development of micropost force sensor array with culture experiments for determination of cell traction forces. AB - Cell traction forces (CTFs) are critical for cell motility and cell shape maintenance. As such, they play a fundamental role in many biological processes such as angiogenesis, embryogenesis, inflammation, and wound healing. To determine CTFs at the sub-cellular level with high sensitivity, we have developed high density micropost force sensor array (MFSA), which consists of an array of vertically standing poly(dimethylsiloxane) (PDMS) microposts, 2 microm in diameter and 6 microm in height, with a center-to-center distance of 4 microm. In combination with new image analysis algorithms, the MFSA can achieve a spatial resolution of 40 nm and a force sensitivity of 0.5 nN. Culture experiments with various types of cells showed that this MFSA technology can effectively determine CTFs of cells with different sizes and traction force magnitudes. PMID- 17342764 TI - Applications of molecular techniques to fine-needle aspiration biopsy. AB - The effectiveness of fine-needle aspiration biopsy (FNAB) for rendering a specific diagnosis can be improved by applying several ancillary modalities. This review details several applications of molecular techniques using FNAB specimens with an emphasis on those used for patient care. A detailed search of the literature was conducted to collect all reports that used FNAB for different types of molecular tests. Several types of molecular tests, including in-situ hybridization, polymerase chain reaction, Southern blotting, and gene microarrays using FNAB specimens have been reported. These tests have been used with different organ systems and different objectives, including the detection of cancer cells, diagnosis, distinction of benign and malignant disease, prediction of response to chemotherapy, risk assessment, and selection of patients for targeted therapy. Except for a few tests such as assessment of HER2/neu for gene amplification in breast cancer, detection of clonality in hematopoietic neoplasms, and specific chromosomal translocations in the former and in the diagnosis of soft tissue sarcoma, most of the molecular tests using FNAB specimens are currently investigational. The reported literature indicates the excellent potential of using material procured from FNAB for almost any type of molecular test. Whereas few of these tests alone are used for patient care, some of them have the potential for clinical use in the near future. PMID- 17342765 TI - Microtubule-binding proteins CLASP1 and CLASP2 interact with actin filaments. AB - Cell morphogenesis requires dynamic communication between actin filaments and microtubules which is mediated, at least in part, by direct structural links between the two cytoskeletal systems. Here, we examined interaction between the CLIP-associated proteins (CLASP) CLASP1 and CLASP2, and actin filaments. We demonstrate that, in addition to a well-established association with the distal ends of microtubules, CLASP2alpha co-localizes with stress fibers, and that both CLASP1alpha and CLASP2alpha co-immunoprecipitate with actin. GFP-CLASP2alpha exhibits retrograde flow in the lamellipodia of Xenopus primary fibroblasts and in the filopodia of Xenopus spinal cord neurons. A deletion mapping analysis reveals that both the microtubule-binding domain of CLASP2 (which is homologous between all CLASPs) and the N-terminal dis1/TOG domain of CLASP2alpha (which is homologous between alpha isoforms) possess actin-binding activity. Fluorescence resonance energy transfer experiments demonstrate significant energy transfer between YFP-CLASP2alpha and CFP-actin. Our results indicate that CLASPs function as actin/microtubule crosslinkers in interphase cells. We propose that CLASPs facilitate recognition of actin filaments by the plus ends of growing microtubules at the initial stages of actin-microtubule interaction. Cell Motil. PMID- 17342766 TI - Outcome of patients with Philadelphia chromosome-positive chronic myelogenous leukemia post-imatinib mesylate failure. AB - BACKGROUND: The prognosis of patients with chronic myelogenous leukemia (CML) after failure of imatinib mesylate therapy is not well documented. METHODS: The outcome of 420 patients with CML post-imatinib failure (resistance-recurrence in 374; toxicities in 46) were reviewed in relation to survival, overall, and by different therapies. RESULTS: The estimated 3-year survival rates were 72% in 88 patients who progressed in chronic phase, 30% in 130 patients who progressed in accelerated phase, 7% in 156 patients who progressed in blastic phase, and 75% in 37 patients in chronic phase with imatinib intolerance. Survival in chronic phase was better when subsequent therapy was nilotinib or dasatinib vs allogeneic stem cell transplant vs others (estimated 2-year survival rates 100% vs 72% vs 67%; P = .01), but not in accelerated-blastic phase. CONCLUSIONS: Prognosis post imatinib failure in chronic phase is reasonable; it is poor if the CML phase post imatinib failure is accelerated or blastic. PMID- 17342767 TI - Expression of caveolin-1 in mucoepidermoid carcinoma of the salivary glands: correlation with vascular endothelial growth factor, microvessel density, and clinical outcome. AB - BACKGROUND: Caveolin-1, which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. The importance of caveolin 1 in endothelial cells in angiogenesis has been confirmed. The clinicopathologic significance of caveolin-1 expression and its correlation with angiogenesis remains unknown in mucoepidermoid carcinoma (MEC) of the salivary glands. METHODS: Based on an immunohistochemical study, the expression levels of caveolin 1 and vascular endothelial growth factor (VEGF) and the intratumoral microvessel density (MVD) (labeled by CD34) in 75 patients with MEC were investigated, and correlations with clinicopathologic variables were evaluated statistically. RESULTS: The expression rates of both caveolin-1 and VEGF were 54.7% (41 of 75 tumors). MVD varied from 9 to 56 (24.45 +/- 10.72)/x 200. Caveolin-1 expression was correlated inversely with duration of tumor, clinical stage, histologic grade, and MVD (P = .027, P = .011, P = .04, and P = .025; respectively). VEGF expression was associated positively with MVD (P = .000). Advanced clinical stage, higher grade, and tumors that originated from minor salivary glands exhibited higher MVD (P = .029, P = .002, and P = .008, respectively). The presence of clinical symptoms, male gender, advanced clinical stage, higher grade, increased MVD, and down-regulated caveolin-1 were correlated significantly with the development of recurrent disease, as indicated by a shorter disease-free interval (P < .05). Both univariate and multivariate analyses indicated that clinical stage, histologic grade, and MVD were independent prognostic factors (P < .05). The presence of clinical symptoms and the down-regulation of caveolin-1 were identified as negative prognostic predictors in the univariate analysis (P < .05) but did not achieve significance in the multivariate analysis (P > .05). CONCLUSIONS: The current results suggest that caveolin-1 may function as a tumor suppressor in MEC of the salivary glands. Reduced expression of caveolin-1 and increased MVD may indicate a poor prognosis for certain patients. PMID- 17342768 TI - Male breast cancer in the veterans affairs population: a comparative analysis. AB - BACKGROUND: The incidence of male breast cancer (MBC) continues to rise. The Veterans Affairs (VA) Central Cancer Registry (VACCR) provides a unique source for the study of MBC. The objective of this retrospective analysis was to compare the characteristics and outcome of patients with MBC and patients with female breast cancer (FBC) in the VA population. METHODS: VACCR data were used to analyze the database of VA patients who had breast cancer diagnosed between 1995 and 2005. It includes 120 VA medical centers. Primary site codes were identified for breast cancer (500-508). Data were entered and analyzed using biostatistical software. RESULTS: In total, 3025 patients' records were reviewed, and 612 patients who had MBC were compared with 2413 patients who had FBC. The mean age at diagnosis was 67 years for patients with MBC and 57 years for patients with FBC (P < .005). More patients with MBC were black, and patients with MBC presented with higher disease stage and more lymph node-positive disease. The dominant histology in MBC was ductal carcinoma. No difference in grade or laterality was observed. Estrogen and progesterone receptor-positive tumors were more common in MBC compared with FBC. Overall, patients with MBC received less chemotherapy, whereas no statistical difference was observed in the use of hormone treatment. The median overall survival for patients who had MBC was 7 years compared with 9.8 years for patients who had FBC (log-rank test; P < .005). There was no statistically significant difference in median survival for patients with stage III disease and stage IV disease. However, the median survival differed significantly for patients with stage I disease and stage II disease. In lymph node-negative patients, the median survival was 6.1 years for patients with MBC and 14.6 years for patients with FBC (P < .005), whereas the median survival did not differ significantly in lymph node-positive patients. Using Cox regression analysis age, sex, clinical stage, and lymph node status were independent prognostic factors for survival, whereas race, histology, and grade were not. CONCLUSIONS: To the authors' knowledge, this is the largest series of MBC and FBC to date in the veterans population. The results suggested the presence of differences in the biology, pathology, presentation, ethnicity, and survival between patients with MBC and patients with FBC in the VA population. It is noteworthy that the survival of patients with MBC was inferior for those with early-stage disease and lymph node-negative tumors, suggesting that there are differences between the sexes in the pathogenesis and biology of breast cancer. In patients with hormone receptor-positive MBC, survival was inferior despite similar hormone treatment practices between MBC and FBC. This observational study calls for a better understanding of this disease that would allow new opportunities for specific therapeutic intervention. PMID- 17342769 TI - Development of an animal model for ovotoxicity using 4-vinylcyclohexene: a case study. AB - BACKGROUND: The occupational chemical 4-vinylcyclohexene (VCH) has been shown to cause destruction of small pre-antral follicles in ovaries of mice. Further, its monoepoxide metabolites, 1,2-VCH epoxide, 7,8-VCH epoxide, and the diepoxide, VCD, have been shown to cause pre-antral follicle loss in rats as well as mice. Chemicals that destroy small pre-antral follicles are of concern to women because exposure can result in premature ovarian failure (early menopause). METHODS: Studies working with these chemicals over the past decade have determined a number of aspects of the mechanism(s) of small pre-antral destruction, and a variety of questions have been answered. RESULTS: Specifically, it has been determined that the diepoxide (VCD) is the bioactive form and it directly targets the ovary in mice and rats. Mice are more susceptible to VCH than rats because they are capable of its metabolic bioactivation. Follicle destruction by VCD is selective for primordial and primary follicles. Mechanistic studies in rats have determined that VCD causes ovotoxicity by accelerating the natural process of atresia (apoptosis) and this requires repeated exposures. Pro-apoptotic signaling events in the Bcl-2 and mitogen activated protein kinase families have been shown to be selectively activated in fractions of small pre-antral follicles (targets for VCD). Finally, a whole ovarian culture system using neonatal mouse and rat ovaries has been developed to expand the potential for more in depth investigations into ovotoxicity caused by VCD. CONCLUSIONS: This article provides an overview of the questions asked and the approaches taken in studying VCH and VCD to support these conclusions. PMID- 17342770 TI - Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall-cell lung cancer: clinical implications for the subsequent management of the brain. AB - BACKGROUND: The incidence and pattern of brain metastases was analyzed among patients who achieved a pathological complete response (pCR) after neoadjuvant chemotherapy or chemoradiotherapy for locally advanced nonsmall-cell lung cancer (NSCLC). METHODS: Between 1990 and 2004, 211 patients were treated with neoadjuvant therapy before surgical resection for stage III NSCLC. The clinical course of 51 patients who demonstrated a pCR were reviewed. The neoadjuvant regimen consisted of either chemotherapy (29 patients) or chemoradiotherapy (22 patients). Histology was 45% adenocarcinoma, 41% squamous cell, and 14% large cell carcinoma. No patient received prophylactic cranial irradiation (PCI). RESULTS: Overall survival at 1, 3, and 5 years was 82%, 63%, and 42%, respectively. The most common site of initial recurrence was the brain. Twenty two (43%) patients developed brain metastasis as the site of first failure, which represented 71% of all isolated recurrences. Ultimately, 28 (55%) patients developed brain metastases at some point during their clinical course. The 5-year estimates of brain metastasis-free survival for patients with squamous and nonsquamous cancers were 57% and 34%, respectively (P = .02). Median survival from the time of brain metastasis was 10 and 5 months for those with isolated and nonisolated recurrences, respectively. CONCLUSION: Patients with a pCR after multimodality therapy for locally advanced NSCLC are at excessively high risk for the subsequent development of brain metastases. Implications for management strategies including PCI and stereotactic radiosurgery (SRS) are discussed. PMID- 17342771 TI - Evidence for activation of KIT, PDGFRalpha, and PDGFRbeta receptors in the Ewing sarcoma family of tumors. AB - BACKGROUND: The Ewing sarcoma family of tumors (ESFT) is one of the most common malignant neoplasms of children and adolescents, characterized by nonrandom translocations involving the Ewing sarcoma (EWS) gene. Over the years the adoption of intensive multimodality treatment approaches has led to a gradual improvement in the survival of patients with ESFT. The prognosis is still unsatisfactory for high-risk patients, however, and novel therapeutic approaches are desirable. The aim of the study was to investigate the expression/activation of KIT, PDGFRalpha, and PDGFRbeta receptor tyrosine kinases (RTKs) as potential therapeutic targets in ESFT. METHODS: RNA and proteins were extracted from 20 frozen ESFT specimens to ascertain the state activation of KIT, PDGFRalpha, and PDGFRbeta. RESULTS: No mutations were found, whereas the cognate ligands were detected in all cases by polymerase chain reaction (PCR). The expression and activation of KIT, PDGFRalpha, and PDGFRbeta were confirmed by quantitative PCR, immunohistochemistry, and immunoprecipitation and/or Western blot analysis. In particular, when compared with a protein pool obtained from normal adult tissues, PDGFRbeta showed a greater protein expression and/or a stronger phosphorylation signal. CONCLUSIONS: The results are consistent with an autocrine/paracrine loop activation of the KIT, PDGFRalpha, and PDGFRbeta receptors and suggest a rationale for the use of RTK inhibitors, either alone or in combination with chemotherapy. PMID- 17342772 TI - On dichotomizing phenotypes in family-based association tests: quantitative phenotypes are not always the optimal choice. AB - In family-based association studies, quantitative traits are thought to provide higher statistical power than dichotomous traits. Consequently, it is standard practice to collect quantitative traits and to analyze them as such. However, in many situations, continuous measurements are more difficult to obtain and/or need to be adjusted for other factors/confounding variables which also have to be measured. In such scenarios, it can be advantageous to record and analyze a "simplified/dichotomized" version of the original trait. Under fairly general circumstances, we derive here rules for the dichotomization of quantitative traits that maintain power levels that are comparable to the analysis of the original quantitative trait. Using simulation studies, we show that the proposed rules are robust against phenotypic misclassification, making them an ideal tool for inexpensive phenotyping in large-scale studies. The guidelines are illustrated by an application to an asthma study. PMID- 17342773 TI - New method to quantify erythrophagocytosis by autologous monocytes. AB - BACKGROUND: Anemia is the net result of decreased red blood cell (RBC) production and increased removal of RBCs. Replication and maturation of erythroid precursors and RBC lysis can be measured by standardized in vitro methods and surrogate markers, respectively. In contrast, erythrophagocytosis by autologous phagocytes is more difficult to quantify. METHODS: We developed a method to assess erythrophagocytosis by autologous monocytes from 5 ml of whole blood. RBCs were labeled with carboxyfluorescein-diacetate-succinimidyl ester (CFDA-SE) and subsequently coincubated with autologous CD14(+) monocytes. Phagocytosis was quantified using flow cytometry. After standardization, the assay was validated in patients with severe malarial anemia (SMA), a condition that is associated with increased erythrophagocytosis. RESULTS: After labeling, CFDA-SE was stably incorporated into RBCs and no significant leakage leading to contamination of nonlabeled cells was observed. Monocytes ingested opsonized, labeled RBCs seven times more than nonopsonized controls. Erythrophagocytosis was significantly higher in SMA than in healthy controls. CONCLUSIONS: The established assay showed enhanced autoerythrophagocytosis associated with SMA and hence was able to detect clinically relevant erythrophagocytosis. This novel assay is well suited for rapid quantification of in vitro erythrophagocytosis by autologous monocytes. PMID- 17342774 TI - Alterations of centromere positions in nuclei of immortalized and malignant mouse lymphocytes. AB - BACKGROUND: The three-dimensional (3D) positions of centromeres have been studied in several cell systems. However, data on centromere positions during cellular transformation remain elusive. This study has focused on mouse lymphocytes and investigated the centromere positions in primary, immortalized, and tumor cells. METHODS: Eighty-to-ninety z-slices of each mouse lymphocyte nucleus were acquired using a sampling distance of 107 nm in the xy plane and 200 nm along z for each z stack, using an Axioplan 2 microscope, an AxioCam HR CCD, a 63x/1.4 oil objective, and the Axiovision 3.1 software (Carl Zeiss, Canada). A constrained iterative algorithm (Schaefer et al., J Microsc 2001;204:99-107) was used for deconvolution. Centromere positions in 3D images were analyzed using CentroView, a program we developed to measure nuclear centromere positions. RESULTS: Using CentroView we determined the positions of centromeres in primary lymphocytes, immortalized and malignant mouse B cells. We show that centromeres exhibit altered nuclear positions in immortalized and malignant B cells. These changes are independent of previously described cell cycle-dependent centromere dynamics. CONCLUSIONS: The 3D positions of centromeres are altered during cellular transformation. In lymphocytes, centromeres are found in more central nuclear positions following immortalization and transformation. These nuclear changes reflect structural remodeling of mammalian nuclei during oncogenesis and may impact on the structural organization of chromosomes. How centromeric changes are linked to nuclear remodeling can now be quantitatively examined using the tools of this study. PMID- 17342775 TI - Flow analysis and sorting of microchromosomes (<3 Mb). AB - BACKGROUND: The analysis and isolation of high numbers of chromosomes smaller than 3 Mb in size (microchromosomes) with good purity is dependent primarily on the detection sensitivity of the flow cytometer and the precision of the sort unit. The aim of this study was to investigate the capability of using a conventional flow cytometer for the detection and sorting at high purity microchromosomes with an estimated size of 2.7 Mb. METHODS: Chromosomes were isolated from a human cell line containing a pair of X-derived microchromosomes, using a modified polyamine isolation buffer. The chromosome preparation was labeled with Hoechst and Chromomycin and analyzed and purified using a MoFlo sorter (DAKO) configured for high-speed sorting. The purity of the flow-sorted microchromosomes was assessed by reverse chromosome painting. RESULTS: Improved resolution of the peak of microchromosomes in a bivariate plot of Hoechst versus Chromomycin fluorescence was obtainable after discriminating clumps and debris based on gating data within a FSC versus pulse width plot. CONCLUSIONS: Chromosomes of smaller size, less than 3 Mb, can be detected with high resolution and flow-sorted with high purity using a conventional flow sorter. PMID- 17342776 TI - Two-generation reproduction study of di-2-ethylhexyl terephthalate in Crl:CD rats. AB - BACKGROUND: This study was conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) on reproductive capability from exposure of F(0) and F(1) parental animals. METHODS: Four groups of male and female Crl:CD (SD)IGS BR rats (30/gender/group) were exposed to 0, 0.3%, 0.6%, and 1.0% DEHT in the feed for at least 70 consecutive days before mating for the F(0) and F(1) generations. Exposure for the F(0) and F(1) males continued throughout the mating period until euthanasia. Exposure for the F(0) and F(1) females continued throughout mating, gestation, and lactation. The F(1) and F(2) pups were weaned on postnatal day (PND) 21. Assessments included gonadal function, estrous cyclicity, mating behavior, conception rate, gestation, parturition, lactation, and weaning in the F(0) and F(1) generations, and F(1) generation offspring growth and development. RESULTS: DEHT exposure did not affect clinical observations. However, lethality was observed in F(0) and F(1) dams consuming the 1.0% diet during the post-weaning period. No treatment-related mortality occurred in any of the male groups exposed to DEHT or in the female groups exposed to 0.3% or 0.6% DEHT. Male rats consuming the 1.0% diet in both parental generations gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in either the F(0) or F(1) generation. Male and female mating and fertility indices, pre-coital intervals, spermatogenic endpoints, reproductive organ weights, lengths of estrous cycle and gestation, live litter size, developmental landmarks, and postnatal survival were similar in all exposure groups. Additionally, ovarian follicle counts for the F(1) females in the high-exposure group were similar to the control values. No adverse exposure-related macroscopic pathology was noted at any exposure level in the F(0) and F(1) generations. CONCLUSIONS: Increases in liver weights were found in the male and female animals exposed to 0.6% or 1.0% DEHT in the diet. Because there were no accompanying histopathologic changes, this effect was not considered adverse. Significant decreases in feed consumption in the female animals from the groups consuming 1.0% DEHT in the diet during lactation accompanied reduced postnatal pup body weights and rate of weight gain. Reductions in pup body weights later in lactation may also have been due to direct consumption of the treated feed by the pups or taste aversion to the same. Reduced relative spleen weight was found in male weanling pups from the 1.0% group in both generations and reduced relative spleen and thymus weights were found in female pups from the 1.0% group in the F(2) generation at necropsy on PND 21. Therefore, for parental and pup systemic toxicity, 0.3% DEHT in the diet (182 mg/kg/day) was considered no-observed-effect level (NOEL). The 1.0% DEHT (614 mg/kg/day) in the diet exposure concentration was considered a NOEL for F(0) and F(1) reproductive toxicity endpoints. PMID- 17342777 TI - The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies. AB - While an evaluation of the estrous cycle in laboratory rodents can be a useful measure of the integrity of the hypothalamic-pituitary-ovarian reproductive axis, it can also serve as a way of insuring that animals exhibiting abnormal cycling patterns are disincluded from a study prior to exposure to a test compound. Assessment of vaginal cytology in regularly cycling animals also provides a means to establish a comparable endocrine milieu for animals at necropsy. The procedure for obtaining a vaginal smear is relatively non-invasive and is one to which animals can become readily accustomed. It requires few supplies, and with some experience the assessments can be easily performed in fresh, unstained smears, or in fixed, stained ones. When incorporated as an adjunct to other endpoint measures, a determination of a female's cycling status can contribute important information about the nature of a toxicant insult to the reproductive system. In doing so, it can help to integrate the data into a more comprehensive mechanistic portrait of the effect, and in terms of risk assessment, may provide some indication of a toxicant's impact on human reproductive physiology. PMID- 17342779 TI - Interaction between rod and cone inputs in mixed-input bipolar cells in goldfish retina. AB - One class of goldfish bipolar cells, the mixed-input bipolar cell, contacts both rods and cones. Although the morphology of the different mixed-input bipolar cell subtypes has been described, insight into the interaction between rods and cones at the bipolar cell level is scarce. The aim of this study was to characterize this interaction in the different physiological types of mixed-input bipolar cells. We found mixed-input bipolar cells that depolarized, hyperpolarized, or showed a combination of the two types of response after center stimulation. The relative contributions of rod and cone inputs varied strongly in these cell populations. Depolarizing mixed-input bipolar cells are rod-dominated, having the highest sensitivity and the smallest dynamic range. Hyperpolarizing mixed-input bipolar cells, on the other hand, have a more balanced rod-cone input ratio. This extends their dynamic range and decreases their sensitivity. Finally, opponent mixed-input bipolar cells seem to be mostly cone-dominated, although some rod input is present. The antagonistic photoreceptor inputs form a push-pull system that makes these mixed-input bipolar cells very sensitive to changes in light intensity. Our finding that spectral tuning changes with light intensity conflicts with the idea that the separate non-opponent and opponent channels are related to coding of brightness and color, respectively. The organization of mixed-input bipolar cells into various classes with different dynamic ranges and absolute sensitivities might be a strategy to transmit information about all visual aspects most efficiently, given the sustained nature of bipolar cell responses and their limited voltage range. PMID- 17342778 TI - Apoptosis and impairment of neurite network by short exposure of immature rat cortical neurons to unconjugated bilirubin increase with cell differentiation and are additionally enhanced by an inflammatory stimulus. AB - Nerve cell injury induced by unconjugated bilirubin (UCB) has been implicated in brain damage during severe neonatal hyperbilirubinemia, although the molecular mechanisms underlying UCB neurotoxicity are still not clarified. It has been suggested recently that there is an association between hyperbilirubinemia and long-term neurologic dysfunctions. We incubated immature neurons with UCB to evaluate the short- and long-term effects of UCB on apoptotic death and on neuritic outgrowth and ramification. We also evaluated whether mature neurons, exposed previously to UCB in an early stage of differentiation, are more sensitive to apoptosis or to neuritic breakdown when treated with inflammatory agents, such as lipopolysaccharide and tumor necrosis factor-alpha. Results show that exposure of immature neurons to UCB increased apoptosis and provoked a reduction of both neurite extension and number of nodes. These injurious effects observed in immature cells treated with UCB were increasingly perpetuated along cell differentiation, as compared to neurons incubated in the absence of UCB. In addition, neurons that were exposed to UCB when immature showed an increased susceptibility to death by apoptosis, as well as an additional decrease in neurite outgrowth when incubated with an inflammatory agent afterward. This work shows, for the first time, that UCB induces neurite changes consistent with neurodevelopment abnormalities. Furthermore, pre-exposure to UCB followed by an inflammatory stimulus leads to an enhanced susceptibility to long-term apoptosis, as well as a greater neuritic breakdown. These data support the association between neonatal hyperbilirubinemia and the later development of mental illness, such as schizophrenia. PMID- 17342780 TI - Opposing short- and long-term effects on muscarinic M1/4 receptor binding following chronic phencyclidine treatment. AB - Phencyclidine (PCP) is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Several studies have demonstrated that chronic NMDA receptor antagonist treatment in humans and animals can cause long-term behavioral changes that are reminiscent of negative and cognitive schizophrenia-like symptoms. The muscarinic cholinergic system, which is associated with cognitive functions, has been hypothesized to contribute to PCP's mechanism of action. No study, however, has examined the status of M1/4 receptors in the PCP model of schizophrenia. The aim of the present study was to investigate the effects of chronic (14 day) PCP treatment on mouse brain M1/4 receptors in the short term (1 hr and 24 hr) and long term (14 days) after last PCP administration. [(3)H]pirenzepine was used to target M1/4 receptors. In the short term following chronic PCP treatment, M1/4 binding was significantly increased in regions of the limbic system, caudate putamen, cortex, and thalamus (ranging from 56% to 368%), compared with saline treated mice. There were no differences in binding between mice treated with PCP for 14 days and sacrificed 1 hr or 24 hr after the final PCP treatment. In the long term following chronic PCP treatment, M1/4 binding was significantly decreased in all of the above-mentioned brain regions (ranging from 31% to 72%), except in the thalamus, which showed no change. These findings in the long-term group are similar to those reported in post-mortem studies of patients suffering from schizophrenia. PMID- 17342782 TI - Novel approaches to the experimental charge density of vitamin B12. PMID- 17342781 TI - Kainic acid triggers oligodendrocyte precursor cell proliferation and neuronal differentiation from striatal neural stem cells. AB - Glutamate is an excitatory amino acid that serves important functions in mammalian brain development through alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionate (AMPA)/ kainate receptor stimulation. Neural stem cells with self-renewal and multilineage potential are a useful tool to study the signals involved in the regulation of brain development. We have investigated the role played by AMPA/kainate receptors during the differentiation of neural stem cells derived from fetal rat striatum. The application of 1 and 10 microM kainic acid increased significantly the phosphorylation of the cyclic AMP response element binding protein (CREB), raised bromodeoxyuridine incorporation in O4-positive oligodendrocyte precursors, and increased the number of O1-positive cells in the cultures. Increased CREB phosphorylation and proliferation were prevented by the AMPA receptor antagonist 4-4(4-aminophenyl)-1,2-dihydro-1-methyl-2 propylcarbamoyl-6,7-methylenedioxyphthalazine (SYM 2206) and by protein kinase A and protein kinase C inhibitors. Cultures treated with 100 microM kainic acid showed decreased proliferation, a lower proportion of O1-positive cells, and apoptosis of O4-positive cells. None of these effects were prevented by SYM 2206, suggesting that kainate receptors take part in these events. We conclude that AMPA receptor stimulation by kainic acid promotes the proliferation of oligodendrocyte precursors derived from neural stem cells through a mechanism that requires the activation of CREB by protein kinase A and C. In the neurons derived from these cells, either AMPA or kainate receptor stimulation produces neuritic growth and larger cell bodies. PMID- 17342783 TI - Encoding molecular-wire formation within nanoscale sockets. PMID- 17342784 TI - Coexistence of ferroelectricity and ferromagnetism in a rubidium manganese hexacyanoferrate. PMID- 17342785 TI - Ultrasound-induced gelation of organic fluids with metalated peptides. PMID- 17342786 TI - Preparation of a biochip on porous silicon and application for label-free detection of small molecule-protein interactions. AB - A new approach for the preparation of a biochip on porous silicon and the application of the biochip for detection of small molecule-protein interactions with desorption/ionization on porous silicon (DIOS) was demonstrated. The galvanostatically etched porous silicon substrates were chemically modified firstly to yield carboxylic acid terminated surfaces, and then the protein was covalently attached to the surface through amide bonding. By applying a solution of candidate chemicals to the surface and a subsequent wash step, the masses of captured compounds could be analyzed by DIOS. DIOS has advantages of being a direct detection tool compared to the classic fluorescence or chemiluminescence methods, because the process of labeling molecules employed in the fluorescence or chemiluminescence methods can sometimes alert the properties of the labeled molecule. The recognition between proteins and their binding partners is efficient and selective. A good tolerance to disturbance and high enrichment factor of the biochip to the analytes was observed. As an on-chip-based approach, the demonstrated method has a potential to perform in a high-throughput format. PMID- 17342787 TI - Distinction of gaseous soot precursor molecules and soot precursor particles through photoionization mass spectrometry. AB - Samples were drawn from sooting premixed low-pressure ethylene oxygen flames and investigated through photoionization mass spectrometry using either KrF or ArF lasers as the radiation source. With the former, mass spectra were obtained as described in the literature and characterized through a series of signal groups, one for each C-number and extending to about m/z 1000, assigned as a PAH series. When the ArF laser was used the same series was observed with a somewhat higher sensitivity. In addition, a new series was observed overlaid on the PAH series and starting at about m/z 680. The new series exhibited abundant ions and it completely dominated the spectrum beyond m/z 1000. This series was identified as being the spectrum of soot precursor particles. Through measurement of the ionization order it was concluded that at least two photons are needed for ionization of PAHs whereas the particles need only one photon. Consequently, they can be measured with high sensitivity when an ArF laser is used as the radiation source. Furthermore, the discrimination of soot precursor molecules and soot precursor particles becomes possible through photoionization and this enables an improved understanding of the mass spectra. This should allow a particle growth mechanism to be deduced in the near future. PMID- 17342788 TI - Meta-analysis of putative human bornavirus sequences fails to provide evidence implicating Borna disease virus in mental illness. AB - All Borna disease virus (BDV) sequences derived from human specimens published till date were thoroughly analysed and compared to sequences of BDV laboratory strains and to BDV sequences from animals which succumbed to classical Borna disease (BD). Despite high sequence conservation of the BDV genome, animal derived BDV sequences clustered according to their geographic origin. However, in marked contrast, human-derived BDV sequences did not cluster according to their geographic origin but showed high sequence identities to BDV laboratory strains and animal-derived BDVs handled in the laboratories reporting the human strains. Japanese, US, Australian and French human-derived BDV sequences proved to be identical or very similar to animal-derived BDV sequences from Germany, although the human specimens were collected hundreds to thousands of miles away from the central European BD endemic regions. These findings suggest that previous studies linking BDV to human neuropsychiatric disease may have been compromised by inadvertent sample contamination. PMID- 17342789 TI - Assessment is not enough: a randomized controlled trial of the effects of HRQL assessment on quality of life and satisfaction in oncology clinical practice. AB - The potential benefits of health-related quality of life (HRQL) assessment in oncology clinical practice include better detection of problems, enhanced disease and treatment monitoring and improved care. However, few empirical studies have investigated the effects of incorporating such assessments into routine clinical care. Recent randomized studies have reported improved detection of and communication about patients' concerns, but few have found effects on patient HRQL or satisfaction. This study examined whether offering interpretive assistance of HRQL results would improve these patient outcomes. Two hundred and thirteen participants with metastatic breast, lung or colorectal cancer were randomly assigned to one of three conditions: usual care; HRQL assessment or HRQL assessment followed by a structured interview and discussion. Interviews about patients' assessment responses were conducted by a research nurse, who then presented HRQL information to the treating nurse. HRQL and treatment satisfaction outcomes were assessed at 3 and 6 months. No significant differences were found between study conditions in HRQL or satisfaction. Results suggest that routine HRQL assessment, even with description of results, is insufficient to improve patient HRQL and satisfaction. It is suggested that positive effects may require supplementing assessment results with specific suggestions for clinical management changes. PMID- 17342791 TI - The risk for PTSD: new findings. New studies explore the high rate of post traumatic stress disorder (PTSD) in women and an unexpected association between IQ and PTSD risk. PMID- 17342790 TI - Efficacy of aromatherapy (Lavandula angustifolia) as an intervention for agitated behaviours in Chinese older persons with dementia: a cross-over randomized trial. AB - BACKGROUND: Agitated behaviours among persons with dementia are distressing to both patients and their caregivers. As pharmacological interventions may be limited by their potentially adverse effects, the use of complementary therapies for treatment of agitation has become more popular and aromatherapy is the fastest growing one. OBJECTIVES: This study investigates the effectiveness of lavandula angustifolia (lavender) in treating agitated behaviours of demented people in Hong Kong. METHODS: It was a cross-over randomized trial. Seventy Chinese older adults with dementia were recruited; half were randomly assigned to the active group (lavender inhalation) for three weeks and then switched to control group (sunflower inhalation) for another three weeks; the other half did the opposite. Clinical response was evaluated using the Chinese versions of Cohen Mansfield Agitation Inventory (CCMAI) and Neuropsychiatric Inventory (CNPI). RESULTS: The mean CCMAI total scores decreased from 24.68 to 17.77(t=10.79, df=69, p<0.001). The CNPI scores changed from 63.17 (SD=17.81) to 58.77 (SD=16.74) (t=14.59, df=69, p<0.001) after receiving Treatment A (Lavandula Angustifolia). There were no period and sequential effects noted. CONCLUSION: In summary, lavender is effective as an adjunctive therapy in alleviating agitated behaviours in Chinese patients with dementia. In a patient population particularly vulnerable to side effects of psychotropic medications, aromatherapy using lavender may offer an alternative option. PMID- 17342792 TI - Act, don't think, to relieve depression. PMID- 17342794 TI - Blinded side-to-side comparison of topical corticosteroid and tacrolimus ointment in children with moderate to severe atopic dermatitis. AB - There is little information on the relative efficacy of topical tacrolimus and corticosteroids in the treatment of atopic dermatitis (AD) in children. In a single-centre, prospective, observer-blinded, side-to-side comparative study (ISRCTN65507338), 96 children with moderately severe AD were enrolled. The study aimed to compare the relative effectiveness of the child's usual topical corticosteroid with 0.03% tacrolimus ointment applied for 1 week, and if there was no difference, 0.1% tacrolimus ointment applied for a further week. Topical tacrolimus was found to be more effective than topical corticosteroid in 72 of the 93 children (77%) who completed the study. Using multiple-regression analysis with age, gender, pretreatment surface area affected and pretreatment corticosteroid potency as covariants, the only factor that reduced the chance of observing a beneficial effect with tacrolimus was moderate or potent topical corticosteroid use (OR = 0.13; 95% CI 0.02-0.74). PMID- 17342795 TI - [Nicotine substitutes during pregnancy]. PMID- 17342796 TI - Paraneoplastic pemphigus associated with CD20-positive follicular non-Hodgkin's lymphoma treated with rituximab: a third case resistant to rituximab therapy. AB - Paraneoplastic pemphigus is an IgG-mediated disease characterized clinically by a polymorphous blistering eruption with severe mucosal involvement associated with an underlying or occult malignancy. It is associated with high mortality, and response to treatment is generally poor. Potent immunosuppression is often necessary to control progression of the disease. Three case reports have documented successful treatment of paraneoplastic pemphigus with rituximab, an anti-CD20 monoclonal antibody. However, two previous reports have noted that rituximab was unsuccessful in halting progression of PNP. We report a third case of paraneoplastic pemphigus associated with follicular non-Hodgkin's lymphoma in which rituximab was not effective. Whether rituximab is an effective and novel treatment for paraneoplastic pemphigus remains undecided. PMID- 17342797 TI - Novel CDH3 mutations in hypotrichosis with juvenile macular dystrophy. AB - BACKGROUND: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse and short hair, heralding progressive degeneration of the retinal pigment epithelium, which leads to blindness by the second decade of life. The disorder is caused by mutations in CDH3, a gene encoding P-cadherin, a major component of adherens junctions. Most HJMD cases reported to date have been shown to be caused by homozygous CDH3 mutations segregating in consanguineous families. AIM AND METHODS: To elucidate the genetic basis of HJMD in two nonconsanguineous families, we established the coding sequence of CDH3 in four patients and their healthy siblings. RESULTS: The four patients demonstrated markedly variable degrees of visual acuity impairment. Novel biallelic recessive mutations were identified in all affected individuals. One patient in the first family was found to carry two heterozygous mutations, IVS2 + 1G-->A and p.E504K; the other three patients in the second family were compound heterozygous for a missense mutation, p.H575R, and a nonsense mutation, p.R221X. CONCLUSION: This paper expands the spectrum of known mutations in CDH3 and points to the existence of clinical heterogeneity in this syndrome. PMID- 17342798 TI - Variable response of hidradenitis suppurativa to infliximab in four patients. PMID- 17342799 TI - Intravenous immunoglobulin is effective as a sole immunomodulatory agent in pyoderma gangrenosum unresponsive to systemic corticosteroids. PMID- 17342800 TI - Halo phenomenon in neurofibromas and generalized vitiligo in a patient with neurofibromatosis type 1. PMID- 17342801 TI - A case of penile verrucous carcinoma associated with cutaneous horn. PMID- 17342802 TI - Trichoblastoma and syringocystadenoma papilliferum arising in naevus sebaceous in a 4-year-old boy. PMID- 17342803 TI - Painful cutaneous metastasis in a patient with laryngeal adenocarcinoma. PMID- 17342804 TI - Henna causes life-threatening hyperbilirubinaemia in glucose-6-phosphate dehydrogenase deficiency. PMID- 17342805 TI - Humoral hypercalcaemia of malignancy associated with primary cutaneous squamous cell carcinoma. PMID- 17342806 TI - Proceedings of the Bjorntorp Symposium on Stress, Obesity, and Metabolic Syndrome, a satellite symposium to the 39th Annual Scientific Meeting of the European Society of Clinical Investigation. April 9-10, 2005. Athens, Greece. PMID- 17342808 TI - Abstracts of the 9th Congress of the European Society for Sexual Medicine, Vienna, Austria, 3-6 December 2006. PMID- 17342807 TI - Abstracts of the Sexual Medicine Society of North America 2006 Fall Meeting, Las Vegas, Nevada, USA. PMID- 17342809 TI - Reports of the 4th International Workshop on Genotoxicity Testing (IWGT). September 9-10, 2005. San Francisco, California, USA. PMID- 17342810 TI - Major themes in flowering research. Proceedings of a symposium in honor of Georges Bernier. April 2006. Canterbury, United Kingdom. PMID- 17342812 TI - Abstracts from the 2007 Bone Marrow Transplantation Tandem Meetings (ASBMT, CIBMTR), February 8-12, 2007, Keystone, Colorado, USA. PMID- 17342811 TI - Current awareness in prenatal diagnosis. PMID- 17342813 TI - Fostering social work gerontology competence. Proceedings of the First National Gerontological Social Work Conference. March 1, 2003. Atlanta, Georgia, USA. PMID- 17342814 TI - Practice advisory: utility of surgical decompression for treatment of diabetic neuropathy: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. PMID- 17342815 TI - Abstracts of the 58th Annual Conference of the German Society for Hygiene and Microbiology (DGHM), Wurzburg, Germany, 1-4 October 2006. PMID- 17342816 TI - Viewpoint: Kate Brown, MRCP. Interview by Emma Baines. PMID- 17342817 TI - History of cardiology: Defibrillation. PMID- 17342818 TI - In tribute to Luigi Castagnetta-drawings. A narrative approach for children with cancer. AB - In troublesome situations, each of us uses verbal communication carefully, at times diminishing our meaning with words of little significance. However, since the need to communicate remains a part of us, body language or other forms of expression are put into use. Inside a hospital a child is always a stranger with regards to the uneasiness that accompanies his/her experience. Because diagnostic and therapeutic ends are the primary concern of the health care professionals, there is often little sign of affection in their impersonal gestures, glances and body language. Graphic and pictorial communication, therefore, hold great importance for sick children since this is an area they have easier access to, and that they cultivate at school and through play. This activity fulfills their innate need to communicate with themselves and with others. Children express themselves through drawings, using them as a stage to dramatize their needs, wishes anxieties, and joys. When in hospital, children are afraid, and they feel embarrassed around strangers and even parents, especially when the parents are speaking with their caregivers. The children are afraid of making a poor impression and of being rejected by adults, of being considered inadequate and untruthful. Their need for truth and for communication unfolds through artistic expression, and this is the basis of art therapy. The opportunity to express themselves through drawings is what makes the ill child his/her won therapeutic agent through a self-healing mechanism. This may be further guided so as to lead to an increase in self-esteem, which in turn will lead to both enhancement of their full expressive possibilities and to positive feedback of their self-image. In addition to verbal language itself, art therapy is the preferred and ideal means to communicate following the rules of "narrative-based medicine", and to understand children. In this study spontaneous drawings of 50 Italian children affected by leukemia or cancer in different stages were evaluated during 2003 at the outpatient clinic of G. Gaslini Children's Hospital. Ages ranged from 4 to 14 years (median 8 years); 27 were males and 23 females. They drew in three situations: spontaneously when they were alone; with play workers; and with the psychologist. Pictures emerging from these settings have proven to be significant and denote the children's perception of the disease, and of their fears and hopes. The children's drawings allowed them to depict their present and future relationship with the disease, with the hospital, and with the environment in general. Their pictures reflected not only their current state of mind, but also past experiences and future prospects. Art therapy proved to be a vitally important means of "narrative" communication for severely sick children in hospital. Thus, collecting and evaluating drawings in an attempt to establish the intellectual, cultural, and emotional status of each child is of paramount importance. To this end, workers have been trained to carefully observe ech child while drawing. Such extremely important collaboration prevents the loss of relevant and vital details. This research confirms our theory that art therapy has to be included in the total care of a severely ill child while in hospital. Drawings accompanied by comments certainly provide a broader approach to better understanding the child's anxiety and feelings. PMID- 17342821 TI - [Oral care for elderly people]. PMID- 17342822 TI - [Molecular imaging of in-vivo ROS generation in oxidative diseases using ESRI and OMRI]. PMID- 17342823 TI - [Treatment for scabies]. PMID- 17342824 TI - [Guidelines for end-of-life care for older residents living in care facilities]. PMID- 17342825 TI - New skin cancer drug. PMID- 17342826 TI - New treatment for diabetes. PMID- 17342827 TI - First drug to treat irritability associated with autism. PMID- 17342828 TI - Test to help diagnose HIV-1 infection. PMID- 17342829 TI - New hepatitis B treatment. PMID- 17342830 TI - Disability among older Americans continues significant decline. PMID- 17342831 TI - Silicone gel-filled breast implants approved. AB - After rigorous scientific review, the Food and Drug Administration has approved the marketing of silicone gel-filled breast implants made by two companies for breast reconstruction in women of all ages and breast augmentation in women ages 22 and older. The products are manufactured by Allergan Corp. of Irvine, Calif., and Mentor Corp. of Santa Barbara, Calif. PMID- 17342832 TI - Cancer drugs. Weighing the risks and benefits. AB - Few deliberations have greater bearing on human health than when the Food and Drug Administration weighs the risks and benefits of drugs designed to treat life threatening diseases, such as cancer. PMID- 17342833 TI - Bacteria-eating virus approved as food additive. AB - Not all viruses harm people. The Food and Drug Administration has approved a mixture of viruses as a food additive to protect people. The additive can be used in processing plants for spraying onto ready-to-eat meat and poultry products to protect consumers from the potentially life-threatening bacterium Listeria monocytogenes (L. monocytogenes). PMID- 17342834 TI - Keeping up with vaccines. PMID- 17342835 TI - Study: half of people at high risk unaware they need a flu shot. AB - Many people at high risk of flu infection mistakenly believe they're in a low risk group and, as a result, are much less likely to get a flu shot, according to a researcher from the University of North Carolina (UNC) at Chapel Hill School of Public Health. PMID- 17342836 TI - HHS, FDA announce new tools for the nutrition facts label. AB - The U.S. Department of Health and Human Services (HHS) and the Food and Drug Administration's Center for Food Safety and Applied Nutrition (CFSAN) have unveiled two new learning tools to help consumers use the Nutrition Facts label to choose nutritious foods and to achieve healthy weight management. PMID- 17342837 TI - The FDA takes action against unapproved drugs. AB - Most prescription drugs marketed in the United States have been reviewed and approved by the Food and Drug Administration as required by law. Thousands of unapproved prescription drugs, however, are still being prescribed and sold. The FDA, as part of its drug safety efforts, is bolstering its efforts against unapproved drugs in the United States. PMID- 17342838 TI - Warning label added to common blood thinner: how to stay safe. PMID- 17342839 TI - Heart-stopping news. PMID- 17342840 TI - Rehab eases life with low vision. PMID- 17342842 TI - The rise and rise of green chemistry in China. Interview by Nicola Nugent. PMID- 17342841 TI - Boosting desire: what works for women. PMID- 17342843 TI - A natural selection. PMID- 17342844 TI - Developing diagnostics. PMID- 17342845 TI - Dedicated to detection. Interview by Alison Stoddart. PMID- 17342846 TI - Indigenous suicide in New Zealand. AB - This article describes patterns of suicide and attempted suicide among the indigenous (Maori) population of New Zealand using official data from the New Zealand Health Information Service (NZHIS). The majority of Maori suicides (75%) occurr in young people aged <35 years. Rates of suicide are higher among Maori males and females aged <25 than in their non-Maori peers. Rates of hospitalization for attempted suicides are higher amongst Maori males aged 15-24, compared to non-Maori. In contrast, suicide is virtually unknown amongst older Maori (60 years). This article reviews explanations for the observed rates of suicide in Maori, and examines approaches to effective intervention to reduce rates of suicide in young Maori. PMID- 17342847 TI - [It happened... From prebiotic chemistry to human evolution. In Florence, the First Congress of S.I.B.E. September, 4-6, 2006]. PMID- 17342848 TI - A DFT computational study of spin crossover in iron(III) and iron(II) tripodal imidazole complexes. A comparison of experiment with calculations. AB - B3LYP* functionals were used to model the sixteen iron(II) (1A, LS and 5T, HS) and iron(III) (2T, LS and 6A, HS) complexes of the 1 : 3 Schiff base condensate of tris(2-aminoethyl)amine and imidazole-4-carboxaldehyde, H3L1, and its deprotonated forms, [H2L1]1-, [HL1]2-, and [L1]3-. This ligand system is unusual in that [FeH3L1]3+, [FeH3L1]2+ and [FeL1]- all exhibit a spin crossover between 100-300 K. This makes these complexes ideal for a hybrid DFT computational approach and provides an opportunity to refine the value of the exact exchange admixture parameter, c3, and to predict properties of partially protonated complexes that are not experimentally available. The accepted value of 0.20 is larger than the value of approximately 0.13 that was found to best reproduce experimental data in terms of spin state predictions. With iron(III) B3LYP calculations showed that all of the complexes were low spin at 298 K with the exception of [FeH3L1]3+ which is spin crossover in agreement with experimental results. It was also shown for iron(III) that the ligand field increased as the number of protons decreased. In contrast all of the iron(II) complexes were close to the spin crossover region regardless of protonation state. Experimental structures are fairly well modeled by this system in regard to the key structural indicators of spin state, which are the bite and trans angles. The calculated iron to nitrogen atom distances are always larger in the high spin form than the low spin form but all iron to nitrogen bond distances are larger than the experimental values. In general non-bonded interactions are not well modeled by this methodology. PMID- 17342849 TI - Surviving unspeakable trauma: numbing the inner life. PMID- 17342850 TI - Maltreatment, attachment, and resilience in the orphans of Duplessis. PMID- 17342851 TI - Commentary on "Seven institutionalized children and their adaptation in late adulthood: the children of Duplessis". PMID- 17342852 TI - Comentary on "Seven institutionalized children and their adaptation in late adulthood: the children of Duplessis". PMID- 17342853 TI - Case studies of the orphans of Duplessis: the power of stories. PMID- 17342854 TI - Les Enfants de Duplessis: perspectives on trauma and resiliency. PMID- 17342856 TI - Is membrane transport of FFA mediated by lipid, protein, or both? Mechanisms and regulation of protein-mediated cellular fatty acid uptake: molecular, biochemical, and physiological evidence. PMID- 17342855 TI - Commentary on "Seven institutionalized children and their adaptation in late adulthood: the children of Duplessis". PMID- 17342857 TI - Sugar solutions. Interview by James Mitchell Crow. PMID- 17342859 TI - Same old story? PMID- 17342860 TI - 2006 drug approvals: finding the niche. PMID- 17342858 TI - Probing expression. PMID- 17342861 TI - An audience with... Carlo Incerti. Interview by Sabine Louet. PMID- 17342862 TI - Clinical forecasting in drug development. PMID- 17342863 TI - Sitagliptin. PMID- 17342864 TI - [Fertility transition in the industrial basin of the Charleroi area in the 19th century: actors and motivations]. PMID- 17342865 TI - [Woman, a full actor in industrialization: Seraing, 1946-80]. PMID- 17342866 TI - [The Great War for tubercular soldiers: hospitals and sanatoriums]. PMID- 17342867 TI - The London YMCA: a haven of masculine self-improvement and socialization for the late-Victorian and Edwardian clerk. PMID- 17342868 TI - A healthcare legend among legends. Mentor, friend, consummate salesman Charles S. Lauer leaves a large legacy. PMID- 17342869 TI - A review of mortality maps included in the annual reports on vital statistics for Ireland, 1864-1998. AB - Since 1864, some 135 reports have been produced examining marriages, birth and deaths for Ireland. The reports produced during the period prior to World War I are notable for the maps and charts that are included and the level of detail provided. Recent reports have failed to include mortality maps, while those produced since 1950 generally show a declining level of detail. PMID- 17342870 TI - War in the nursery, 1798: the persecuting breast and the melancholy babe in Maria Edgeworth's ennui. PMID- 17342871 TI - The tender mother and the faithful wife: theater, charity, and female subjectivity in eighteenth-century Ireland. PMID- 17342872 TI - The denialists: the dangerous attacks on the consensus about H.I.V. and AIDS. PMID- 17342873 TI - Reviewing peer review: the three reviewers you meet at submission time. PMID- 17342874 TI - Language abilities and nonverbal IQ in children with language impairment: inconsistency across measures. AB - The present study used correlation analyses to examine the extent to which language abilities are associated with nonverbal IQ in 30 children with language impairment, age 4-8 years. After controlling for age, nonverbal IQ demonstrated medium associations with composite measures of both semantic and morphosyntactic abilities (r = .46 and .45 respectively). However when only criterion-referenced measures of language were included in the analyses, no significant associations between language and nonverbal IQ were observed. In addition, individual difference scores between language and nonverbal IQ revealed that discrepancies occurred in both directions--with language exceeding nonverbal IQ in some cases and nonverbal IQ exceeding language in others. In sum, the relatively inconsistent associations between language and nonverbal IQ provided additional reason to question current practices, such as cognitive referencing and the definition of specific language impairment. Implications in regard to theoretical accounts of language impairment are also discussed. PMID- 17342875 TI - Intelligibility in dysarthria: effects of listener familiarity and speaking condition. AB - This study examined the effects of familiarization and speaking condition on sentence intelligibility for a speaker with dysarthria secondary to a traumatic brain injury (TBI). Familiarization procedures included hearing the speaker read a paragraph or a word list comprised of a random ordering of the words in the paragraph. Such an approach allowed for statements concerning the benefit of prior exposure to a sentence-level prosody and word level articulatory-acoustic patterns versus only word-level articulatory-acoustic patterns. Following word list, paragraph, or no familiarization, listeners orthographically transcribed sentences in either a habitual, slow, fast, or loud condition. Listeners receiving either word list or paragraph familiarization accurately transcribed a higher percentage of words in sentences than listeners receiving no familiarization. Intelligibility scores did not differ for word list or paragraph familiarization, however. Listeners also were more accurate transcribing sentences produced in the loud condition compared to habitual and fast conditions. Clinical implications are discussed. PMID- 17342876 TI - Production of /sh/ in trochaic and nontrochaic weak contexts. AB - This study examined whether young children produce an emerging sound (/s/) more accurately in a weak syllable if the syllable is trochaic (i.e., in a strong-weak syllable pattern) than if it is nontrochaic (i.e., either preceding a strong syllable or following another weak syllable). Eight typically-developing 28- to 32-month-old children who sometimes misproduced /s/ imitated three-syllable nonwords with /s/ as the onset in five syllable types: (a) word-medial stressed, (b) word-medial unstressed following a stressed syllable (i.e., trochaic), (c) word-initial nontrochaic, (d) word-medial nontrochaic, and (e) word-final nontrochaic. As predicted, /s/ was more accurate in trochaic than nontrochaic contexts. Among nontrochaic contexts, /s/ was more accurate in word-final position than in word-initial or word-medial positions. Production of /s/ in word final nontrochaic syllables was similar to that in word-medial trochaic syllables. Metrical structure and final syllable prominence together predicted which weak syllables are most likely to contain consonant errors. PMID- 17342877 TI - Volumetric measurements of vocal tracts for male speakers from different races. AB - Research examining physiologic and acoustic characteristics of culturally diverse populations is sorely needed, but rarely reported. The major aim of this study was to quantify vocal tract dimensional parameters (oral length, oral volume, pharyngeal length, pharyngeal volume, total vocal tract length and total vocal tract volume) of adult male speakers from three different racial populations (White American, African American, and Chinese). It also attempted to investigate if volumetric differences in the speakers' vocal tracts, like length differences, would contribute to the acoustic characteristics of these speakers from different races. The findings of this study support the hypothesis that speakers from different races may have morphological differences in their vocal tract dimensions, and these morphological differences (especially volumetric differences) could be partially responsible for the formant frequency differences in a vowel sound void of specific language/dialectal impacts. The study has provided speech scientists, speech-language pathologists, linguists and other health professionals with a new and preliminary acoustic and physiological database for adult male speakers from these three different races. PMID- 17342878 TI - Phonetic difficulty and stuttering in English. AB - Previous work has shown that phonetic difficulty affects older, but not younger, speakers who stutter and that older speakers experience more difficulty on content words than function words. The relationship between stuttering rate and a recently-developed index of phonetic complexity (IPC, Jakielski) was examined in this study separately for function and content words for speakers in 6-11, 11 plus-18 and 18 plus age groups. The hypothesis that stuttering rate on the content words of older speakers, but not younger speakers, would be related to the IPC score was supported. It is argued that the similarity between results using the IPC scores with a previous analysis that looked at late emerging consonants, consonant strings and multiple syllables (also conducted on function and content words separately), validates the former instrument. In further analyses, the factors that are most likely to lead to stuttering in English and their order of importance were established. The order found was consonant by manner, consonant by place, word length and contiguous consonant clusters. As the effects of phonetic difficulty are evident in teenage and adulthood, at least some of the factors may have an acquired influence on stuttering (rather than an innate universal basis, as the theory behind Jakielski's work suggests). This may be established in future work by doing cross-linguistic comparisons to see which factors operate universally. Disfluency on function words in early childhood appears to be responsive to factors other than phonetic complexity. PMID- 17342879 TI - The acute effects of dairy calcium intake on fat metabolism during exercise and endurance exercise performance. AB - The purpose of this study was to test the effect of acute dairy calcium intake on exercise energy metabolism and endurance performance. Trained female runners completed two trials. Each trial consisted of a 90-min glycogen depletion run followed by a self-paced 10K time trial, conducted one hour after consumption of a high dairy (500 mg Ca+2) or low dairy (80 mg Ca+2) meal. During the 90-min run, blood samples and respiratory gases were collected. No treatment main effects of acute dairy intake were found for respiratory exchange ratio (RER), calculated fat oxidation, lactate, glycerol, or 10K time. Following this protocol, acute dairy calcium intake did not alter fat utilization or endurance performance in trained female runners. PMID- 17342880 TI - Effects of an exercise program and a calcium supplementation on bone in children: a randomized control trial. AB - We investigated the effects of calcium supplementation and physical practice on the bone ultrasound properties and trabecular microarchitecture in children. 160 children aged 8-11 were randomly allocated to active or nonactive groups and to receive either a calcium-phosphate or a placebo powder for 6 months. Skeletal status was assessed using an ultrasound technique, which measures the speed of sound (Ad-SoS, m/s) at the phalanx. Bone microarchitecture was characterized by fractal analysis measured on calcaneus radiographs and the result expressed as the Hmean parameter, that has been shown to a good reliability of the bone texture quality. After 6 months, the calcium group had significantly gained Ad SoS compared to the placebo group (P = 0.01) and Hmean increase was greater in the active than the nonactive group (P < 0.05). Exercise and calcium supplementation had a differential effect on the bone tissue, calcium being rather linked to a systemic effect whereas exercise has acted better onto the skeletal stressed site. PMID- 17342881 TI - Effects of a fixed dietary intake on changes in red blood cell delta aminolevulinate dehydratase activity and hemolysis. AB - This study was to assess the effect of a fixed dietary intake on biomarkers of red blood cell (RBC) biosynthesis and degradation. Over a two-year period, eight collegiate rhythmic gymnasts participated in this study. During the first year, they ate self-selected diets. During the second year, a fixed dietary intake involving consumption of common Japanese foods containing 15 mg iron and 1500 kcal energy was maintained for 4 wk at the beginning of the program. Fixed dietary intakes resulted in significantly increased intakes of protein, minerals and vitamins, and significantly decreased fat intake, but total energy and carbohydrate intakes were unchanged. Mean values of RBC, Hb, Ht, or TIBC were not affected by the intervention. A fixed dietary intervention appeared to enhance RBC turnover by increasing the capacity for erythrocyte biosynthesis and degradation, although the prevalence of iron-deficiency anemia remained unchanged. PMID- 17342882 TI - The timing of fluid intake during an Olympic distance triathlon. AB - Seven highly trained male triathletes, aged 18 to 35 years, were tested during two simulated Olympic distance triathlons to determine whether run performance was enhanced when consuming 177 ml of water at 8, 16, 24, and 32 kilometers (Early Trials) compared to consumption at 10, 20, 30, and 40 kilometers (Late Trials), during the cycling segment of the triathlon. Swim times for 1500 m were similar between trials; 40-km cycling times were approximately 10 s faster during the Late Trials; however, 10-km run times were faster during the Early Trials (P < 0.02). No significant differences between run trials were found for the rating of perceived exertion, oxygen uptake, heart rate, and change in urine specific gravity. It was concluded that the consumption of fluids earlier in the cycle phase of the Olympic distance triathlon benefits the run and overall performance time. PMID- 17342883 TI - Effects of amino acid supplementation on muscle soreness and damage. AB - This study investigated the effect of a supplement containing 9 essential and 3 non-essential amino acids on muscle soreness and damage by comparing two endurance exercise bouts of the elbow flexors with amino acid or placebo supplementation in a double blind crossover design. The supplement was ingested 30 min before (10 h post-fasting) and immediately after exercise (Experiment 1), or 30 min before (2-3 h after breakfast), immediately post, and 8 more occasions over 4-day post-exercise (Experiment 2). Changes in muscle soreness and indicators of muscle damage for 4 days following exercise were compared between supplement conditions using two-way ANOVA. No significant differences between conditions were evident for Experiment 1; however, plasma creatine kinase, aldolase, myoglobin, and muscle soreness were significantly lower for the amino acid versus placebo condition in Experiment 2. These results suggest that amino acid supplementation attenuates DOMS and muscle damage when ingested in recovery days. PMID- 17342884 TI - Patterns of ephedra and other stimulant use in collegiate hockey athletes. AB - This study examined trends in stimulant use and attitudes toward use among American collegiate hockey athletes. All 139 players in one college hockey conference completed a comprehensive questionnaire. Over half of the athletes (51.8%) confirmed stimulant use before a hockey game or practice. About half of the respondents (48.5%) reported having used ephedra at least one time to improve athletic performance. Additionally, 17.4% reported using pseudoephedrine to improve performance in the 30 days prior to survey administration. Over half (55.4%) were aware of the recent national ban on ephedra. Fifty-nine percent stated the national ban made them less likely to use ephedra products. The majority of athletes began use prior to college. Coaches, athletic trainers, and team physicians should be aware of athletes' patterns of stimulant use. Improved educational efforts directed at younger athletes are necessary to deter abuse of metabolic stimulants. PMID- 17342885 TI - Fluid guidelines for sport: interview with Professor Tim Noakes. Interview by Louise M. Burke. PMID- 17342886 TI - [Laboratory diagnosis of paraproteinaemia]. AB - The results of laboratory tests carried out in normal hospital practice for the diagnosis of monoclonal hypergammaglobulinaemia (paraproteinaemia) are discussed. PMID- 17342887 TI - [The effect of ionising radiations on human chromosomes]. AB - A brief explanation of the dangers inherent in the indiscriminate use of ionising radiations and a description of the modality of action of cell radiations are followed by an account of the significance of lesions of the genetic inheritance. Data obtained from the irradiation of human chromosomes are also presented. In these experiments, the effects of scalar doses on in vitro peripheral blood cultures and 'in vivo' on patients irradiated in the course of treatment of the lumbosacral area were studied. The radioprotective activity of various pharmacological agents was measured by means of an original method and the results obtained are discussed. PMID- 17342888 TI - [The treatment of severe neonatal icterus]. AB - The aetiopathogenesis of icterus is briefly examined and stress is laid on the immaturity of the neonatal and particularly of the immature infanti liver. A limit is then set between paraphysiological and serious icterus and the symptoms of neonatal hyperbilirubinaemia with or without nuclear icterus are recalled. Attention is drawn to the debated problem of the bilirubin threshold value and the different and often conflicting views of the various schools are cited. Caution is urged since the nervous damage must be evaluated even over periods of years. The techniques employed in the determination of bilirubin values are then discussed and the associated difficulty of settling the threshold level is noted; standardisation of methods is to be hoped for and reference is made to personal experience of considerable differences between venous and capillary blood when the latter is expressed. Treatment of the disease has been attempted with various substances, some (cortisones, albumin) with notable others (triiodothyronine, polyvinylpyrrolidone) with little success; the use of anti-D sera and immunoglobulins in Rh-negative mothers as a means of prevention of neonatal jaundice is also noted. Personal experience (113 subjects) with phototherapy is resorted and the complete absence of short or long term damage is noted. 3 1/2 years experience with exsanguinotransfusion is also presented: 57 cases (0.7% of births; mortality rate 3.5%). In 40% of these cases bilirubin values had passed the 20 mg % threshold (max. 36%); only one patient presented early and late signs of damage. PMID- 17342889 TI - [Crouzon's craniofacial dysostosis]. AB - A brief account of craniofacial synostosis is presented. The cranium is acrocephalic owing to the early closure of the coronal and lambdoid sutures. The crown is typically rudimentary where the anterior fontanel is still open. Cranial radiography shows digitate markings. Skeletal changes lead to hypertelorism, exophthalmos and strabismus. The nose is of the parrot's beak type and the hypoplasic upper jaw is in contrast with the lower jaw, resulting in pseudo prognathism. These basic malformations are accompanied by several other deformities. The disease may appear as a hereditary or as a sporadic occurrence. The cases described in the present paper confirm the hereditary interpretation of the syndrome, since both were accompanied by positive familial histories. In the first case, the signs of the disease were less evident, whereas in the second the picture was complete and both mother and daughter presented impressive examples of the frog face sign. PMID- 17342890 TI - [3 cases of Pierre Robin syndrome]. AB - An account of the main features (micrognathia, glossoptosis and cleft palate) and aetiopathogenetic interpretation of Pierre Robin's syndrome, as well as the various types of treatment that have been employed, is followed by a description of 3 personal cases (all typical examples and without concomitant abnormalities). The presence of cleft palate in the grandmother and mother of one patient is seen as evidence in favour of the hereditary transmission of the disease. The more or less rapidly fatal outcome of all 3 cases, in spite of positional therapy, suggest that the prognosis for this syndrome is very poor, notwithstanding the more favourable opinion expressed by other writers. PMID- 17342891 TI - [A case of Apert's syndrome]. AB - The main features of acrocephalosyndactyly (Apert's syndrome) are described. Early closure of the coronal suture leads to the vertical development of the cranium (turricephaly), with flattening of he frontal and occipital bones. In the neonate. the anterior fontanelle extends from the glabella to the posterior fontanelle. The face takes on a flat appearance, the root of the nose is inset and there are abnormalities of the orbital cavity (hypertelorism, exophthalmos, oculomotor paralysis, optic atrophy). The palate is high and deep. Malformations of the extremities consist primarily in more or less complete syndactyly (usually characterised by the presence of a single ungueal lamina), with spoon-shaped hands and spatulate feet. Impairment of intelligence is often observed. Pathogenetically speaking, the syndrome may be sporadic or familial. Treatment is briefly described and an account of a sporadic-type personal case is given. Reference is also made to the relationship between Apert's and Crouzon's syndrome and to a prior description of two familial cases of the latter disase. PMID- 17342892 TI - [Anatomical, clinical and surgical features of total and partial patellectomy in the treatment of comminuted fractures of the kneecap]. AB - An account of the literature data relating to total and partial patellectomy in the management of comminuted kneecap fractures is followed by a theoretical and practical discussion of the pros and cons of the two techniques. It is shown that total resection does not lead to serious functional disturbances in spite of its alteration of the shape of the knee; on the other hand, partial resection, although more in keeping with the physiological situation, may lay the seeds of femoropatellar arthrosis. PMID- 17342893 TI - [Aetiopathogenetic, clinical and statistical aspects of coccygodynia]. AB - The Protean clinical and aetiopathogenetic features of coccygodynia are discussed. The causes and pathogenetic mechanisms of this disease, together with its dependence on or concomitance with other forms, are not fully understood, with the result that treatment cannot be precisely prescribed. In most cases, indeed, treatment is more often entrusted to the mental attitude and specialist activity of the person whose task it is to handle the particular pathological situation than based on a sound knowledge of the real nature of events of this kind. The study of a meaningfully large case series shows that greater precision is required in reaching a diagnosis in each particular case; it also points to the very limited indications for radical surgery. PMID- 17342895 TI - [Exsanguinotransfusion at the Holy Cross Hospital, Cuneo]. AB - A brief reference to the criteria employed in the selection of candidates for exsanguinotransfusion (bilirubinaemia threshold), and a short account of the medical and physical treatment of serious neonatal icterus are followed by a description of personal exsanguinotransfusion experiences. 57 cases have been treated in this fashion in 3 1/2 years, 20 from centres in the province and 37 (0.72% of births) from children both at the Obstetrics Division of the Cuneo Hospital. 32 patients were born at term, the remainder were immature. The indications for treatment included 4 cases of pathological icterus resulting from the reabsorption of haematoma (3 of these cases presented indirect bilirubin values above the 20 mg % threshold). The mean mortality index was 3.5%. Complications were confined to: (immediate), one case of thromboembolism of a lower limb; (late) frequent chronic exudative-type enteropathy. Of 20 subjects whose indirect bilirubin values had surpassed the 20 mg% threshold (with values as high as 36 mg %) before treatment, one only presented signs of cerebral lesion (aphasia, with intelligence unimpaired). PMID- 17342894 TI - [Serum immunoglobulin behaviour in the immature infant from birth to 2 years]. AB - A brief account of immunity (fundamental stages of the process, part played by the dependent and independent thymus system, importance of the lymphocyte, theories concerning the interpretation of the antibody response) and of the immunoglobulins (the G-A-M-D-E classification and the features and functions of each class), together with a note relating to mother-foetus transmission of immunity) and the autochthonous origin of Ig, are followed by the presentation of data obtained in 28 female and 27 male immature infants (divided into 3 groups on a body weight basis) studied from birth to 2 yr. The results were as follows: IgG behaviour as in the mature child, but low with respect to the adult in proportion to the degree of immaturity. Transient increase (between 10th and 30th day) followed by regular catabolism (min. 4th-6th month). Slow recovery to 50 % and little over 60 % adult values at 1 and 2 yr; IgA - absent at birth, appearing at about 20th day. Rapid increase to 3 months, slight fall to 5th month, with slow recovery to slightly less than 3rd month values (= 31-45% adult) at 1 yr and slightly over the same at 2 yr: this pattern differs from the literature data; IgM--always present at birth, rapid increase in proportion to immaturity during first few days. Decrease from 20th day to 3rd-6th month (only twice reported in the literature) followed by slow recovery to 60% adult values at 1 yr. The overall picture is of precocious antibody (IgM) response broken by a transient fall between the 3rd and 5th due to catabolism of maternal IgG coupled with inadequate autochthonous production of IgG and temporary decrease in autochthonous IgA and IgM values. These findings suggest, inter alia, that the vaccination calendar be shifted to the 6th month to ensure adequate response. PMID- 17342896 TI - [Phototherapy in the treatment and prevention of serious icterus in the neonate]. AB - Ten years ago, treatment of serious icterus in the neonate was made more effective by the addition of a new method: the employment of the hypobilirabinaemising effect of light. The mechanism of degradation lying behind this action is not vet fully clear; there can be no doubt, however, that the method is convenient, practical and harmless. Personal results obtained in 1 yr of work in this field are reported. 113 subjects (77% of whom were immature) were treated. The ratio of treated subjects to number of births was 7% (ratio between exsanguinotransfusion and birth values, 0.7%). The means consecutive exposure time has been 48 hours but they arrived also 7 days exposure and there were no cases of immediate or long-term damage. 25% of the treated subjects presented an almost always slight bilirubinaemic rebound. The normal degradation rhythm was 0.2 mg/hr and 0.1 mg/hr on the first and second day respectively. In cases of icterus due to reabsorption of haematoma, however, a 25% above-average degradation rhythm was observed. PMID- 17342897 TI - [Cytomorphology of the bronchial secretion in hyperplastic, metaplastic and tumoral lesions of the lung]. AB - Cytomorphological examination, following fixing in paraffin and staining with haematoxin-eosin, of expectorated material from 20 cases of suspected pulmonary lesions is reported. 4 cases proved positive for bronchogenic carcinoma, 2 presented flat epithelial cells referable to squamous metaplasia and 1 revealed voluminous cells attributable to bronchial adenoma. Biopsy confirmed the cytological evidence in the positive neoplasia cases while indirect confirmation of the accuracy of the negative findings was given by the clinical course and subsequent follow-up of individual patients. Reference to the literature data concerning cytological pulmonary diagnosis is followed by a discussion of differential diagnosis problems in various bronchial diseases, attention being particularly given to some of the more fundamental biological features connected with the histogenesis of malignant epitelial tumours, especially squamous metaplasia; the latter may be observed in TB, in bronchiectasia, in abscesses and in association with carcinoma. PMID- 17342898 TI - [Vaccination as a prophylactic weapon in the fight against tetanus]. AB - Statistical evidence relating to tetanus morbility and mortality in Italy and in the world as a whole is presented and the essential part played by vaccination in the eradication of this disease is emphasised. A detailed discussion of the recent legislation introducing compulsory vaccination for certain categories of the population is followed by some suggestions for the improvement of the existing measures with a view to carrying of a truly effective campaign against tetanus on the medical and social scale. PMID- 17342899 TI - [Vaginal secretion hyaluronidase activity levels in normal and in some pathological conditions. Physiological pictures in a clinical series]. AB - A viscometric method was used to determine vagina hyaluronidase activity in 82 healthy subjects. Enzyme values (in micrograms) were referred both to a volume unit and to a standard protein unit. Each subject was also examined colposcopically, cytologically, bacteriologically and cytohormonally. Three subject groups (premenopause, menopause, senile) and three subgroups relating to commonly observed cytological pictures in benign lesions of the portio uteri were chosen. The results show a fall in concentration values from the first to the third group; no meaningful differences were observed in either the individual or the overall subgroup values. PMID- 17342900 TI - [Perinatal mortality at the S. Anna Obstetrical-Gynaecological Hospital of Turin. Remarks on the last five year period (1963-1967)]. AB - The perinatal mortality observed at the S. Anna Obstetrical and Gynaecological Hospital of Turin in the five year period (1963-1967) is presented. After a survey of the literature on the subject its causes are examined. A cooperation among specialists of the various medical branches is hoped in view of a solution of this serious problem. PMID- 17342901 TI - [A case of allergy due to the use of an egg yolk vehicle in artificial insemination]. AB - A case of allergy resulting from the employment of citrated homogenized egg yolk in homologous insemination is reported. The allergen was identified with the presence of egg yolk in the insemination vehicle. The various primary and secondary causes of the syndrome are discussed and the medical therapy used is described. It is suggested that intradermal skin reaction test be carried out with the individual components of the vehicle before artificial insemination with egg yolk-based vehicles is performed. PMID- 17342902 TI - [Bronchopulmonary signs in the course of Giardia lamblia infestation in infancy]. AB - Four cases of Giardia lamblia infestation in infants aged between 6 months and 2 years and accompanied by bronchopulmonary signs are presented. Data from the literature are cited and the clinical and therapeutic data from the reported cases are relied upon for the view that this parasite may be responsible for symptoms involving the respiratory apparatus. PMID- 17342903 TI - [A case of swelling of the right breast lasting from birth was observed in a two year-old boy]. AB - A secretion was collected from the nipple and was examined. Hirsutism and abnormal pigmentation were lacking, and the aspect of the external genitalia was normal. The cromatin sex was male. The sella turcica had a normal roentgenologic aspect. The urinary 17-ketosteroid and oestrogen excretion was normal. The swelling was removed surgically. A histologic diagnosis of gynaecomasty was made. The differential diagnosis, classification and physiopathology of gynaecomasty are discussed. PMID- 17342904 TI - [Serum immunoglobulin values in some diseases of infancy]. AB - Serum immunoglobulin behaviour in some infantile diseases of immunological interest has been studied. No differences in Ig class values were observed in cases of rickets. Intestinal malabsorption was accompanied by increased IgA values, whereas other writers have reported steady or even decreased values in this disease. IgG and IgM increases are observed in virus hepatitis. In line with the majority of the literature reports, decreased IgM values were observed in mongolism. PMID- 17342905 TI - [Serum immunoglobulin patterns in some diseases of infancy]. AB - Following a previous note dealing with rickets, intestinal malabsorption, virus hepatitis and mongolism, the present paper deals with serum immunoglobulin behaviour in thymomegaly, nephrosis and response to TAB vaccination. Thymomegaly was accompanied by increases in all three Ig classes, followed by normalisation of values shortly after steroid treatment. in nephrotic proteinuria, determination of glomerular selectivity via the evaluation of IgG and transferrin clearance was of assistance with respect to prognosis and therapy. Artificial antigen stimulation of healthy and mongoloid subjects with TAB vaccine was not followed by differences in Ig class behaviour; similar stimulation of full-term and immature neonates, however, showed a rapid and frank increase in immature IgM values with respect to the non-stimulated immature subject of equal age and weight. PMID- 17342906 TI - [Economic and medicosocial implications of an ageing population]. AB - Reference is made to recent statistics in an analysis of the problems presented by an ageing population, with particular emphasis on the economic and medicosocial consequences. An account is given of the most suitable therapeutic and prophyletic approaches to the question, as well of medicosocial programmes which give due weight to the true meaning of geriatric problems. PMID- 17342907 TI - [The use of artificial pacemakers in medical practice]. AB - Reference is made to personal experience in the treatment of atrioventricular block with asynchronous pacemaker in a consideration of the criteria to be employed in their surgical indication. The results obtained were good, even over a long period of time. It is, however pointed out that, in spite of the improvements that have been made in recent years, breakdowns of the electrostimulator are the most common form of complication; none the less, correction is almost always a matter of little difficulty. PMID- 17342908 TI - [35S investigation of the effect of benzopiperylone on sulphuretted mucopolysaccharides in experimentally induced granuloma]. AB - The influence of a synthetic anti-inflammatory drug, benzipiperylone, on 35S dynamics was studied in experimentally induced (cotton-pellet) granuloma. The anti-inflammatory activity of the drug was confirmed by the demonstration of depressed tracer elimination rates. PMID- 17342909 TI - [Complications of ophthalmic herpes zoster]. PMID- 17342910 TI - [The effect of taurine as a protector of human marrow cells against radiation]. AB - Chromosome fragmentation counts on irradiated human marrow cells were used to determine the radioprotective effect of taurine. The results were unifavourable in the sense that the number of fragmentations observed in cultures to which taurine had been added was only slightly less than that in the control cultures. PMID- 17342911 TI - [Medicosocial aspects of ankylosing spondylitis]. AB - The position of ankylosing spondylitis among rheumo-arthropathies of medicosocial interest is discussed and the elements of the disease anabling an early diagnosis to be made are described, viz. the outstanding clinical and radiological features. Emphasis is placed on the importance of rationally planned pharmacotherapeutic and re-educative treatment in preventing the progress of the disease towards irreversible and highly invaliding pictures. PMID- 17342912 TI - [Some aspects of the rehabilitation and social reinstatement of the amputee]. AB - The problem of the re-education and reinstatement of the amputee is considered. Reference is made to various aspects of cases occurring on account of congenital or acquired abnormalities in children and of those involving the aged. A more detailed account is given of various aspects of amputation carried out in subjects whose capacity for work is otherwise unimpaired. Emphasis is laid on the need for selective evaluation via the collaboration of both medical and paramedical personnel in every attempt to achieve satisfactory social and occupational reinstatement. PMID- 17342913 TI - [Blood and liver fat values in rats kept on a hyperlipid, hypoprotein, steatogenous diet, with or without choline]. AB - Serum and liver tissue fatty acid and lipid fraction values were studied in rats kept for various periods on a hyperlipid, hypoprotein, steatogenous diet, with or witout choline. There was a general increase in liver fats due to an absolute increase in triglycerides, accompanied by changes in the fatty acid methyl ester composition, indicating the storage of lipids of lesser metabolic activity and more similar to those of peripheral fat (palmitic and oleic acid increments; decreases in myristic, stearic, linoleic and arachidonic acid values). These changes were partly reflected in the blood picture: little difference in lipid fraction ratios, coupled with fatty acid gas chromatograms similar to those observed for the liver. The omission of choline aggravated the alterations caused by the experimental diet. PMID- 17342914 TI - [Experimental cirrhosis of the liver obtained with simultaneous carbon tetrachloride and phenobarbital sodium]. AB - Phenobarbital sodium considerably increases the liver toxicity of CCl4. The onset and course of cirrhosis induced by simultaneous oral phenobarbital sodium and inhaled CCl4 were studied in a large number of rats. The apparatus and method used are described. The results observed are expressed in terms of survival, variations in liver and spleen weight, and the gross and microscopic liver picture. The method is considered for optimal for the rapid induction of marked and typical cirrhosis in the rat. PMID- 17342915 TI - [Free aminoacids and cerebral lipids in the rat following porto-cava anastomosis]. AB - Free aminoacids and cerebral lipids were studied in rats following porto-cava anastomosis with total deviation of the portal flow. No difference in lipid pattern with respect to the controls was noted after 1 month. Changes in free aminoacids, however, were observed, including a significant increase in gamma aminobutyric acid (GABA) and a significant decrease in glutamic acid. The meaning of these results with respect to the pathogenesis of porto-cava encephalopathy is discussed. PMID- 17342917 TI - [Notes of some cases of dermatoses observed in the canning industry]. AB - A form of dermatosis noted amongst female workers in the canning industry is described and shown to be a disease of occupational origin, though not classed among the technopathies recognised by the INAIL. PMID- 17342916 TI - [Modern criteria for the choice of dialysis monitors]. AB - The tasks required of a modern dialysis monitor are explained and the parameters that it supervises are described. Ways in which the maximum degree of safety can be assured are discussed and the criteria applicable the choice of equipment for routine hospital, home and research use are indicated. PMID- 17342918 TI - [Anthropological aspects of the foot]. AB - The adoption of an erect posture was an important step in human evolution for its consequent redimensioning of organisms and functions, in addition to its strictly evolutionary results. Formation of the sole to provide three-point support and better support of the front of the body--this being now deprived of direct support and thus compelled to rest on low-set, rear supports--was accompanied by the release and upward shift of the front limbs for use in tasks, such as gripping and carrying, formerly performed by the jaws; the latter, moreover, regressed so as to cause a variation in favour of the neural as opposed to the facial cranium and an increase in brain capacity, available nerve circuits, and so-called "higher faculties". Intelligence, in the classic sense of "Umschaltungsfahigkeit" is included among the latter. The present study sets a more rational background for flat feet and talipes equinus. These ase seen as signs of a single process, flat feet being a form of extreme hypo-evolution in three orthopaedic degrees, and equinus a manifestation of excessive development in the opposite direction. This contention is supported by comparative evidence, using data from other animal species. In man, various stages involve different races and are dependent on both habits and habitat, or indeed on the need for survival. Extensive references are made to the literature and the subject is updated and viewed as an example of "reasoned evolution". PMID- 17342919 TI - [Histochemical methods in the study of normal and tumoral cells in serous effusions]. AB - The behaviour of intracellular lipids (Sudan black B), PAS positivity peroxidase and hydrolytic enzymes (acid and alkaline phosphatase, aspecific esterases) was studied in normal and tumour cells from serous effusions. It is suggested that the practical application of such method to the diagnosis of effusions should be checked over a wider range of case material. PMID- 17342920 TI - [Clonal chromosome abnormalities in a case of pleural mesothelioma]. AB - The results of a chromosome study carried out on direct pleural effusion material cultures in a patient with malignant mesothelioma are reported. Two 50 chromosome cell populations displaying varied signs of karyotype reworking were noted. These had one and two large submetacentric markers respectively. The value of karyotype studies alongside cytological examinations in all instances of suspect effusion. PMID- 17342921 TI - [Two cases of de Morsier's olfactogenital syndrome]. AB - Two cases of De Morsier's olfactogenital syndrome (complex hypogenitalism and anosmia) are presented. The first patient was of eunuchoid build and presented testicle and penile hypotrophy, depressed adrenal activity and gonad-stimulating pituitary function and distinctly below-normal urinary 17-ketosteroid values. The second subject was gynaecoid, menopausal gonadotrophic hormonal values, short urethra with no radiological signs of the prostate, and gynaecoid upper pelvic basin diameters. The karyotype pattern was normal XY in the first case and XX in the second. It is suggested that embryopathic or genetic changes, probably in the rhinencephalon, led to a direct pituitary nervous short-circuit that impeded normal FSH gonadal stimulation and hence gonadal influence on the phenotype throughout both intra- and extrauterine life, particularly at puberty. PMID- 17342922 TI - [Encephalopathy in the rat following partial portosystemic anastomosis]. AB - Gamma-aminobutyric acid (GABA) values were determined in 4 groups of Sprague Dawley rats 45-50 days after end-to-side porto-cava (PC), mesentericosplenic-cava (MSC) and mesenteric-cava (MC) anastomosis, and a false operation (FO) respectively. Values were significantly increased in the anastomosed animals. If, as may be supposed, this finding points to altered cerebral metabolism, its observation in the MSC and MC groups militates against the general view that encephalopathy in the experimental animal only occurs as a result of total deviation of the portal flow. PMID- 17342923 TI - [In vitro antibiotic sensitivity of 43 B and/or C bile strains of E. coli]. AB - 43 strains of E. coli observed in B and/or C bile from patients in the University of Catania Medical Clinic between 1965 and 1970 were subjected to 16 antibiotics in vitro. Sensitivity to streptomycin fell from 55.86% in 1965 to 16% in 1970, whereas a fluctuation from 35 to 55% was observed for kanamycin over the same period; there was a general fall in effectiveness in the case of the other 14 antibiotics. The clinical advantages nd technical simplicity of the antibiogram are noted. PMID- 17342924 TI - [Aminochlorthenoxycycline levels in experimental acute inflammation of the respiratory tree]. AB - A special technique used to obtain acute respiratory inflammation in the rabbit produced a considerable increase in expectorate by comparison with the controls. Bronchial, lung and blood aminochlorthenoxycycline levels were much higher than in the controls, showing that this antibiotic has a marked affinity for inflamed lung tissue. PMID- 17342925 TI - [Bronchopulmonary aminochlorthenoxycycline levels in experimental burns of the respiratory tree]. AB - A special technique was employed to obtain burns of the respiratory tree in 24 male rabbits, Increased bronchial secretion was observed during the burning. Aminochlorthenoxycycline values were higher in the secretion after 90' than in the controls, while blood and lung concentrations displayed a similar pattern. The usefulness of the drug in the prevention and treatment of infectious complications following burns in this area is stressed. PMID- 17342926 TI - [Some rare cases of dislocation and combined fracture and dislocation of the thumb]. AB - Some rare cases of dislocation and combined fracture and dislocation of the thumb are presented. Some brief remarks concerning their importance with respect to normal hand function are followed by an explanation of the relevant anatomical and radiological pictures and a description of the surgical and conservative treatment employed in each case. PMID- 17342927 TI - [Notes on the mode of action of oncogenic viruses]. AB - Certain fundamental notions concerning virus oncogenesis are reviewed. A brief description of the main morphological features of the more common oncogenic viruses is followed by an account of their mechanism of action and cell and organism factors essentially associated with their induction of tumour growth. Recent hypotheses concerning the virus aetiology of tumours in man are discussed. PMID- 17342928 TI - [Notes on the electrolytic composition of haemodialysis solutions]. AB - Changes in haemodialytic technique have been accompanied by variations in electrolyte content: calcium, sodium, potassium and chlorine levels have been decreased, while that of magnesium has been increased. Modern formulae offer optimal electrolyte with drawal from the patient. It has been shown that even minor changes in electrolyte content are followed by immediate (e.g. sodium increase) or delayed (e.g. calcium increase) symptomatologies with well-defined pathological pictures. While a standard formula for safe use in large groups can be defined, it is desirable to look for composition variants so as to obtain less traumatising treatments and, more particularly, to avoid long-term complications. PMID- 17342929 TI - [Electrophoretic behaviour of serum and liver proteins and of some isoenzymes in rats receiving a steatogenous, hyperlipidic, hypoprotein diet, with and without choline]. AB - Albino rats were kept for long periods on a steatogenous, hypoproteic, hyperlipidic diets, either with or without choline. Serum protein and liver soluble protein and enzyme values showed changes that were only partly similar to those observed in human and experimental cirrhosis. The main features, in fact, were an absolute and percent decrease in albumins, an increase in serum alpha1 globulins and alpha proteins generally, and, more particularly, a constant fall in gamma-globulins and enzymes migrating to this site. PMID- 17342930 TI - [Oestrogens in the stimulation of adrenal steroid production in the rat]. AB - Chronic administration of oestradiol has several times been reported as leading to stimulation of in vitro adrenal hydroxylative activity in the rat. It is now shown that acute stimulation is also possible, provided ACTH is present in the system. Synthetic oestrogens with metabolic activity equivalent to that of oestradiol, however, are incapable of stimulating steroid production. It is clear that the mechanism of action of oestrogens is extremely complicated as far as the adrenal glands are concerned. PMID- 17342932 TI - [Dynamic lung volume in the aged and in obstructive ventilatory insufficiency]. AB - Mid-expiratory maximum flow, maximum expiratory flow rate and maximum expiratory volume per sec. were studied in 66 males aged 42 to 88 yr., including 27 normal subjects and 39 with obstructive respiratory insufficiency to determine the importance and significance of these parameters in the evaluation of dynamic resistance to flow and in the study of the senile lung. PMID- 17342931 TI - [Influence of glucose-6-phosphate dehydrogenase on rat adrenal 11-beta hydroxylase]. AB - Previous work has shown NADPH to be a necessary cofactor in adrenal production of steroids. Synthesis is, in effect, a function of dehydrogenase activity and the adrenals are particularly rich in these enzymes. The present paper deals with an appraisal of the importance of G 6-PD as a source of NADPH for mitochondrial hydroxylation. 11-beta-hydroxylation was used as parameter. It was found that the activity of this enzyme, and hence NAPDH production, was stimulated by the administration of ACTH; no parallel increase in 11-beta-hydroxylase activity was noted. PMID- 17342933 TI - [Clinical and aetiopathogenetic notes on 6 cases of acute amentia in patients with gangrene due to obstruction of the lower extremity arteries]. AB - Six cases of acute amentia in a series of 58 subjects with lower extremity artery obstruction are described and their possible pathogenesis is discussed in the light of present biological, physiopathological and psychopharmacological views. Radical surgery brings resolution of amentia syndromes of this type and its desirability in such cases is stressed. PMID- 17342934 TI - [Notes on cases of carcinoma of the uterine body observed in the S. Anna Hospital, Turin, between 1954-1969 and the Piedmont and Aosta Valley areas in the period 1965-1969]. AB - An increase in the frequency of corpus cancer over the period 1954-1969 and 1965 1969 in records for the S. Anna Hospital, Turin, and the Piedmont and Aosta Valley areas respectively is reported. Attention is drawn to the fact that more than 30% of patients were in the 66-80 age group (i.e. over the usual age of 56 to 60). A higher frequency of infertility and delayed menopause in patients with such tumours has been proved statistically significant. Diabetes, obesity and hypertension are pathogenetically linked to adenocarcinoma of the endometrium and not to casual associations. The findings are in line with the view that this neoplasia is hormone-dependent and a public health programme for its prevention is proposed. PMID- 17342935 TI - [Effects of human gamma-globulins upon some biological activities of human histiocytes and granulocytes]. AB - In a "vivo" treatment with human gamma-globulins does not modify the locomotion rate "in vitro" of macrophages obtained from Rebuck's "skin windows". Oppositely, the same treatment reinforced the phagocytosis and intracellular digestion of stafilococci by peripheral blood granucytes "in vitro" possibly through a specific anticorpal mechanism. PMID- 17342936 TI - [Protective effect of cortisone against the anti-cellular action of endotoxins]. AB - In vitro studies with the phase contrast microscope. The protective effect of sodium 6-methyl-prednisolone hemisuccinate against the effects of a purified Salmonella abortus equi lipopolysaccharide were investigated in the rabbit. The intravenous injection of 8 mg of the cortisone derivative simultaneously with the injection of the endotoxin considerably attenuated the febbrile and leukopenic action of the latter. The rate of locomotion of the leukocytes in the peripheral blood in animals treated with endotoxin or with endotoxin plus cortisone was also investigated. In animals protected by sodium 6-methyl-prednisolone hemisuccinate the endotoxin caused a smaller decrease of speed of migration of the leukocytes than that observed in animals treated with the lipopolysaccharide alone. These findings are discussed in the light of present knowledge of the mechanism of the anti-cellular action of endotoxins and of the protective action of cortisone. PMID- 17342937 TI - [A study of vascular stresses and deformations in relation to variations of the tonus and to their geometrical characteristics]. AB - The stresses and deformations which the blood vessels are subjected in relation to variations of their tonus and their geometrical characteristics are considered. The problema is defined from the physical standpoint. PMID- 17342938 TI - [A study of the distribution of the flow in a branched system of vessels. In parallel system of vessels]. AB - A theoretical physical study of the variations of the distribution of the flow in a branched system of vessels is presented. The possible applications are prospected. PMID- 17342939 TI - [Intercellular substance of connective tissue: collagen and mucopolysaccarides]. AB - The paper deals with the more salient data on the principal components of the intercellular substance of connective tissue: collagen and mucopolysaccharides. With regard to collagen, is described the sub-microscopic structure of single units of "tropocollagen" and the interpretation of the periodic structure of fibrils, their organization in tissue as well as the synthesis and reabsorption of collagen itself is discussed. With reference to mucopolyaccharides, their chemical structure, distribution in the tissues and their relation with the protein component of the protein-polysaccharide complex is described. Furthermore the Author points out the quantitative and qualitative changes of the various mucopolysaccharides in connection with age, site and function. Brief reference is also made to the essential characteristics of sialic acid. PMID- 17342940 TI - [Laboratory examinations in cardiorheumatology]. AB - Specific and aspecific laboratory examinations employed in the investigation of cardiorheumatological disease are reviewed. The principles lying at the basis of the various methods are illustrated and the practical applications and limits of each form of examination are discussed. PMID- 17342941 TI - [Chromosome analysis in 2 cases of Marfan's syndrome]. AB - The results of a chromosome study conducted in 2 cases of Marfan's syndrome are reported. In one case, giant satellite corpuscles on one of the four acrocentrics of pair 21-22 were observed in all mitoses studied; in the other case, no morphologically meaningful changes were noted. PMID- 17342942 TI - [A contribution to the treatment of cancer of the cervix]. AB - An account is given of the latest developments in diagnosis of cancer of the cervix in the pre-invasion stage, and the surgical techniques and most commonly used radiotherapy methods are described. Particular attention is given to radiosurgical therapy and, with this in view, a personal method used in a series of 52 patients is presented: Wertheim's operation is associated with the placing of radium pellets in the stripped parametrium. High survival percents obtained for periods of years, particularly in 2nd and 3rd stage cancers, show the positive effectiveness of the method. PMID- 17342943 TI - [A morphologic study of the liver of rats with organic phosphorus ester poisoning]. AB - The liver of rats with acute poinsoning by organic phosphorus esters was examined. The poison used was 98% Parathion injected subcutaneously (500 mg per kg) in rats kept on a normal or high-protein diet. The morphologic changes in the liver tissue, and the diminution of the glycogein content and the variations of the protein content were less severe in the rats given a high-protein diet than in those given a diet with a normal protein content. The mechanisms of this pathogenetic correlation in poisoning by organic phosphorus esters are discussed, also in the light of the data reported in the literature. PMID- 17342944 TI - [Considerations on the Bennett's fracture]. AB - Seven cases of Bennett's fracture are studied. The pathogenesis, pathological anatomy and various therapies are presented and the method of bloodless therapy illustrated. PMID- 17342945 TI - Test for increasing convex order in multivariate response. AB - Trend test based on cross-classified data in dose-response has been a central problem in medicine. Most of existing test methods are known to only fit to binary response variables. However, the approaches for binary response tables may suffer from the lack of a clear choice for dichotomization. For multivariate response with ordered categories, some studies have been done for simple stochastic order, likelihood ratio order and so on. However, methods of statistical inference on increasing convex order for more than two multinomial populations have not been fully developed. For testing the increasing convex order alternative, this article provides a model-free test method which can be used in the case of two-way tables and stratified data. Two real examples will be used to illustrate how to apply our test method. PMID- 17342947 TI - Development of sequential multiple comparison procedure for dose response test. AB - We propose a multiple comparison procedure to identify the minimum effective dose level by sequentially comparing each dose level with the zero dose level in the dose finding test. If we can find the minimum effective dose level at an early stage in the sequential test, it is possible to terminate the procedure in the dose finding test after a few group observations up to the dose level. Thus, the procedure is viable from an economical point of view when high costs are involved in obtaining the observations. In the procedure, we present an integral formula to determine the critical values for satisfying a predefined type I familywise error rate. Furthermore, we show how to determine the required sample size in order to guarantee the power of the test in the procedure. In practice, we compare the power of the test and the required sample size for various configurations of the population means in simulation studies and adopt our sequential procedure to the dose response test in a case study. PMID- 17342946 TI - Step down procedure for comparing several treatments with a control based on multivariate normal response. AB - In this study we consider a multiple comparison of several treatments with a control based on multivariate normal response in clinical trials. Specifically we construct a step down procedure by referring to Dunnett and Tamhane (1991). Furthermore we formulate the all-pairs power by using the recursive formula derived by Hayter and Tamhane (1991) and Dunnett, Horn and Vollandt (2001). Finally we compare the step down procedure with the single step procedure proposed by Nakamura and Imada (2005) in terms of some numerical examples regarding the power of the test. PMID- 17342948 TI - Step-up related simultaneous confidence intervals for MCC and MCB. AB - The derivation of compatible confidence bounds related to stepwise decision procedures is a serious issue. Especially the derivation of step-up related bounds is rather complex. In this article we consider (one-sided) multiple comparisons with a control (MCC) and multiple comparisons with the best (MCB) with the aim of establishing delta-equivalence to the best and derive step-up related confidence bounds by applying the projection method proposed in Finner and Strassburger (2006). Some examples illustrate the resulting procedures. PMID- 17342949 TI - Applying the generalized partitioning principle to control the generalized familywise error rate. AB - In multiple testing, strong control of the familywise error rate (FWER) may be unnecessarily stringent in some situations such as bioinformatic studies. An alternative approach, discussed by Hommel and Hoffmann (1988) and Lehmann and Romano (2005), is to control the generalized familywise error rate (gFWER), the probability of incorrectly rejecting more than m hypotheses. This article presents the generalized Partitioning Principle as a systematic technique of constructing gFWER-controlling tests that can take the joint distribution of test statistics into account. The paper is structured as follows. We first review classical partitioning principle, indicating its conditioning nature. Then the generalized partitioning principle is introduced, with a set of sufficient conditions that allows it to be executed as a computationally more feasible step down test. Finally, we show the importance of having some knowledge of the distribution of the observations in multiple testing. In particular, we show that step-down permutation tests require an assumption on the joint distribution of the observations in order to control the familywise error rate. PMID- 17342951 TI - Duncan's k-ratio Bayes rule approach to multiple comparisons: an overview. AB - An alternative to frequentist approaches to multiple comparisons is Duncan's k ratio Bayes rule approach. The purpose of this paper is to compile key results on k-ratio Bayes rules for a number of multiple comparison problems that heretofore, have only been available in separate papers or doctoral dissertations. Among other problems, multiple comparisons for means in one-way, two-way, and treatments-vs.-control structures will be reviewed. In the k-ratio approach, the optimal joint rule for a multiple comparisons problem is derived under the assumptions of additive losses and prior exchangeability for the component comparisons. In the component loss function for a comparison, a balance is achieved between the decision losses due to Type I and Type II errors by assuming that their ratio is k. The component loss is also linear in the magnitude of the error. Under the assumption of additive losses, the joint Bayes rule for the component comparisons applies to each comparison the Bayes test for that comparison considered alone. That is, a comparisonwise approach is optimal. However, under prior exchangeability of the comparisons, the component test critical regions adapt to omnibus patterns in the data. For example, for a balanced one-way array of normally distributed means, the Bayes critical t value for a difference between means is inversely related to the F ratio measuring heterogeneity among the means, resembling a continuous version of Fisher's F protected least significant difference rule. For more complicated treatment structures, the Bayes critical t value for a difference depends intuitively on multiple F ratios and marginal difference(s) (if applicable), such that the critical t value warranted for the difference can range from being as conservative as that given by a familywise rule to actually being anti conservative relative to that given by the unadjusted 5%-level Student's t test. PMID- 17342950 TI - Empirical Bayes identification [correction of identication] of tumor progression genes from microarray data. AB - The use of microarray data has become quite commonplace in medical and scientific experiments. We focus here on microarray data generated from cancer studies. It is potentially important for the discovery of biomarkers to identify genes whose expression levels correlate with tumor progression. In this article, we propose a simple procedure for the identification of such genes, which we term tumor progression genes. The first stage involves estimation based on the proportional odds model. At the second stage, we calculate two quantities: a q-value, and a shrinkage estimator of the test statistic is constructed to adjust for the multiple testing problem. The relationship between the proposed method with the false discovery rate is studied. The proposed methods are applied to data from a prostate cancer microarray study. PMID- 17342952 TI - Combining adaptive designs with control of the false discovery rate--a generalized definition for a global p-value. AB - When combining adaptive designs with control of the False Discovery Rate one has to keep in mind that the most frequently used procedure for controlling the False Discovery Rate--the explorative Simes procedure--is a stepwise multiple testing procedure. At the interim analysis of an adaptive design it is however not yet known what the boundaries for rejection of hypotheses in the final analysis will be as these boundaries depend on the size of the final p-values. Therefore classical adaptive designs with a predefined stopping criterion for early rejection of hypotheses are not well suited. We propose a generalized definition of a global p-value for a two-stage adaptive design permitting a flexible decision for stopping at the interim analysis. By means of a simulation study in the field of genetic epidemiology we illustrate how applying such a two-stage design can reduce costs. PMID- 17342953 TI - FDR control by the BH procedure for two-sided correlated tests with implications to gene expression data analysis. AB - The multiple testing problem attributed to gene expression analysis is challenging not only by its size, but also by possible dependence between the expression levels of different genes resulting from coregulations of the genes. Furthermore, the measurement errors of these expression levels may be dependent as well since they are subjected to several technical factors. Multiple testing of such data faces the challenge of correlated test statistics. In such a case, the control of the False Discovery Rate (FDR) is not straightforward, and thus demands new approaches and solutions that will address multiplicity while accounting for this dependency. This paper investigates the effects of dependency between bormal test statistics on FDR control in two-sided testing, using the linear step-up procedure (BH) of Benjamini and Hochberg (1995). The case of two multiple hypotheses is examined first. A simulation study offers primary insight into the behavior of the FDR subjected to different levels of correlation and distance between null and alternative means. A theoretical analysis follows in order to obtain explicit upper bounds to the FDR. These results are then extended to more than two multiple tests, thereby offering a better perspective on the effect of the proportion of false null hypotheses, as well as the structure of the test statistics correlation matrix. An example from gene expression data analysis is presented. PMID- 17342954 TI - An adaptive single-step FDR procedure with applications to DNA microarray analysis. AB - The use of multiple hypothesis testing procedures has been receiving a lot of attention recently by statisticians in DNA microarray analysis. The traditional FWER controlling procedures are not very useful in this situation since the experiments are exploratory by nature and researchers are more interested in controlling the rate of false positives rather than controlling the probability of making a single erroneous decision. This has led to increased use of FDR (False Discovery Rate) controlling procedures. Genovese and Wasserman proposed a single-step FDR procedure that is an asymptotic approximation to the original Benjamini and Hochberg stepwise procedure. In this paper, we modify the Genovese Wasserman procedure to force the FDR control closer to the level alpha in the independence setting. Assuming that the data comes from a mixture of two normals, we also propose to make this procedure adaptive by first estimating the parameters using the EM algorithm and then using these estimated parameters into the above modification of the Genovese-Wasserman procedure. We compare this procedure with the original Benjamini-Hochberg and the SAM thresholding procedures. The FDR control and other properties of this adaptive procedure are verified numerically. PMID- 17342955 TI - Controlling the false discovery rate with constraints: the Newman-Keuls test revisited. AB - The Newman-Keuls (NK) procedure for testing all pairwise comparisons among a set of treatment means, introduced by Newman (1939) and in a slightly different form by Keuls (1952) was proposed as a reasonable way to alleviate the inflation of error rates when a large number of means are compared. It was proposed before the concepts of different types of multiple error rates were introduced by Tukey (1952a, b; 1953). Although it was popular in the 1950s and 1960s, once control of the familywise error rate (FWER) was accepted generally as an appropriate criterion in multiple testing, and it was realized that the NK procedure does not control the FWER at the nominal level at which it is performed, the procedure gradually fell out of favor. Recently, a more liberal criterion, control of the false discovery rate (FDR), has been proposed as more appropriate in some situations than FWER control. This paper notes that the NK procedure and a nonparametric extension controls the FWER within any set of homogeneous treatments. It proves that the extended procedure controls the FDR when there are well-separated clusters of homogeneous means and between-cluster test statistics are independent, and extensive simulation provides strong evidence that the original procedure controls the FDR under the same conditions and some dependent conditions when the clusters are not well-separated. Thus, the test has two desirable error-controlling properties, providing a compromise between FDR control with no subgroup FWER control and global FWER control. Yekutieli (2002) developed an FDR-controlling procedure for testing all pairwise differences among means, without any FWER-controlling criteria when there is more than one cluster. The empirica example in Yekutieli's paper was used to compare the Benjamini Hochberg (1995) method with apparent FDR control in this context, Yekutieli's proposed method with proven FDR control, the Newman-Keuls method that controls FWER within equal clusters with apparent FDR control, and several methods that control FWER globally. The Newman-Keuls is shown to be intermediate in number of rejections to the FWER-controlling methods and the FDR-controlling methods in this example, although it is not always more conservative than the other FDR controlling methods. PMID- 17342956 TI - Operability region equivalence: simultaneous confidence bands for the equivalence of two regression models over restricted regions. AB - In many scientific problems the purpose of comparing two linear regression models is to demonstrate that they have only negligible differences and so can be regarded as being practically equivalent. The frequently used statistical approach of testing the homogeneity null hypothesis of the two models by using a partial F test is not appropriate for this purpose. In this paper, a simultaneous confidence band is proposed which provides an upper bound on the largest possible difference between the two models, in units of the standard error of the observations, over a given region of the covariates. This is demonstrated to be a more practical method for assessing the equivalence of the two regression models. PMID- 17342957 TI - Accounting for multiplicity in the evaluation of "signals" obtained by data mining from spontaneous report adverse event databases. AB - Surveillance of drug products in the marketplace continues after approval, to identify rare potential toxicities that are unlikely to have been observed in the clinical trials carried out before approval. This surveillance accumulates large numbers of spontaneous reports of adverse events along with other information in spontaneous report databases. Recently developed empirical Bayes and Bayes methods provide a way to summarize the data in these databases, including a quantitative measure of the strength of the reporting association between the drugs and the events. Determining which of the particular drug-event associations, of which there may be many tens of thousands, are real reporting associations and which random noise presents a substantial problem of multiplicity because the resources available for medical and epidemiologic followup are limited. The issues are similar to those encountered with the evaluation of microarrays, but there are important differences. This report compares the application of a standard empirical Bayes approach with micorarray inspired methods for controlling the False Discovery Rate, and a new Bayesian method for the resolution of the multiplicity problem to a relatively small database containing about 48,000 reports. The Bayesian approach appears to have attractive diagnostic properties in addition to being easy to interpret and implement computationally. PMID- 17342958 TI - Technology assessment for the anesthesiologist. AB - The expense associated with modern heath care in the United States is very high, in excess of 15% of the GDP, continues to grow and has become a significant public policy issue. New technologies, defined as all drugs, devices, procedures, and organizational systems, are major contributors to rising health care costs. The use of health technology assessment tools can assist those in leadership positions in making rational decisions as to which new technologies to adopt. The classical approach is to use data from prospective, randomized, clinical trials that compare the outcomes of those treated with the new technology and the accepted therapy. Using this information and detailed economic data, the cost effectiveness ratio can be determined. The accepted metrics are either dollars per life year saved or dollars per quality-adjusted life year saved. If the new medical intervention costs less than $50,000 to 80,000 dollars per life year saved, it is considered to be cost-effective and worthy of adoption. This kind of analysis is complex and expensive. In addition, the required information is not always available, limiting the applicability of this approach. Finally, the economic analysis often includes down-stream expense and benefit not relevant from a medical center perspective. Another approach is to focus the analysis to what impacts the medical center. This includes determining whether the technology has received the necessary approvals and has been shown to be effective, to improve health outcomes, to be at least as effective as standard therapy, and to be achievable outside the investigative setting. A fiscal analysis also must be done to determine what will it cost to acquire and operate the technology, what are the anticipated patient volumes and payer mix, and what will be the down stream consequences to the medical center. If the process concludes that the technology works, makes a positive difference to patient care, and is fiscally and operationally acceptable, it should be purchased. After the technology has been installed and has been used, a postimplementation review should be done. This review should go over the same attributes that led to the decision to purchase. It should be determined whether the expected patient volumes, outcomes, income, and expenses were seen. If not, the technology assessment process should be refined to make better decisions in the future. Finally, if the results are at a substantial negative variance from what was anticipated, abandoning the technology should be considered. Anesthesiology either directly controls or indirectly influences a significant portion of medical technology in every medical center. Therefore, the processes that have been discussed in this article should be used by the department of anesthesiology to assure optimal patient care and the fiscal stability of the organization. PMID- 17342959 TI - Electrocardiography: the ECG. AB - This article examines the role of electrocardiography in patient monitoring during an operative procedure. In addition to providing a wealth of physiological information, including information on the electrical activity of the heart, the ECG assists in monitoring and detecting a variety of changes, such as cardiac arrhythmias, electrolyte changes, and ischemia. Information presented on an ECG should be analyzed systematically with an understanding of the constituent elements of an ECG, the rate, the rhythm, the morphology, the axis, the presence of conduction abnormalities, electrolyte changes, and ischemic changes. To assess accurately the information presented, hemodynamic information and cardiac-risk analysis should be integrated to have a complete picture. PMID- 17342960 TI - Arterial and central venous pressure monitoring. AB - Pressure monitoring systems influence the contour of the displayed wave-forms and, on occasion, can introduce significant artifact in the pressure traces. It is important to understand the technical details of invasive pressure monitoring to interpret better the information presented. Careful observation of the arterial pressure waveform can provide information about ventricular function, the arterial system, and ventricular preload. In particular, systolic pressure variation during the respiratory cycle in mechanically ventilated patients is a clinically useful indicator of volume status. CVP monitoring is also used to assess intravascular volume, but this measurement is significantly influenced by ventricular compliance and intrathoracic pressure. Under most clinical circumstances, a trend in CVP values or its change with therapeutic maneuvers is more reliable than a single measurement. Like arterial pressure waveforms, CVP waveform morphology can provide important information about clinical pathophysiology. PMID- 17342961 TI - Intraoperative monitoring with transesophageal echocardiography: indications, risks, and training. AB - There are benefits and risks to the use of TEE. The benefits are derived from the physiologic information that TEE provides, which may not be as readily obtained by any other technique. The risks of TEE are those related to mechanical trauma from the probe, as well as those of an incorrect TEE interpretation by the echocardiographer. Intraoperative TEE is a powerful monitoring and diagnostic tool. Performance of TEE requires special skills. As has been discussed, training guidelines exist. As more clinical studies are published, the indications for intraoperative TEE are likely to expand. Class-I recommendations for intraoperative echocardiography have been listed. The authors have discussed some of the issues involved with each class-I indication. Performance of the TEE is not an end in itself and should not distract the anesthesiologist from the primary goal of patient care. With proper training and experience, the anesthesiologist may learn how to use TEE to improve patient care. PMID- 17342962 TI - Assessment of left ventricular global and segmental systolic function with transesophageal echocardiography. AB - The evaluation of LV global and segmental systolic function is a primary application for perioperative TEE. Although the practical techniques customarily used for these applications have limitations, they afford direct measures of function not otherwise available to the clinician in the operating room or intensive care setting. PMID- 17342963 TI - Noninvasive technologies for tissue perfusion. AB - As outlined in Table 1, the nonthermodilution techniques available to measure cardiac output are noninvasive and clinically applicable to a variable degree. The truly noninvasive monitors are bioimpedance and CO2 re-breathing. The latter, however, requires the patient to be intubated, and the former continues to be evaluated with regard to correlation with the thermodilution standard. Esophageal Doppler devices are relatively noninvasive in that they do not require vascular cannulation, but they do require an immobile patient and some user expertise. Pulse contour analysis requires an arterial catheter, and two of the three available monitors require external calibration, while the third has not been validated adequately. The reader can see that all four approaches continue to be refined, with new analysis algorithms and monitors continuing to appear on the market. In the absence of true tissue oxygenation monitors, it seems likely that some or all of these alternatives to thermodilution will play a greater role in the care of patients where measurement of cardiac output is desired. PMID- 17342964 TI - Monitoring of the brain and spinal cord. AB - IOM has become commonly used by many surgeons to enhance their intraoperative decision making and reduce the morbidity and mortality of selected procedures. The ability to perform these tests rests on the anesthesiologist's ability to provide the patient with an anesthetic plan that provides comfort and monitoring. When events occur, the anesthesiologist's knowledge and ability to manipulate the patient's physiologic condition become integral to the decision making. A good understanding of the neural anatomy, impact of physiology, and anesthetic medications can allow effective IOM and good team decision making when changes in IOM occur. PMID- 17342965 TI - Depth of anesthesia monitoring. AB - Depth-of-anesthesia monitoring with EEG or EEG combined with mLAER is becoming widely used in anesthesia practice. Evidence shows that this monitoring improves outcome by reducing the incidence of intra-operative awareness while reducing the average amount of anesthesia that is administered, resulting in faster wake-up and recovery, and perhaps reduced nausea and vomiting. As with any monitoring device, there are limitations in the use of the monitors and the anesthesiologist must be able to interpret the data accordingly. The limitations include the following. The currently available monitoring algorithms do not account for all anesthetic drugs, including ketamine, nitrous oxide and halothane. EMG and other high-frequency electrical artifacts are common and interfere with EEG interpretation. Data processing time produces a lag in the computation of the depth-of-anesthesia monitoring index. Frequently the EEG effects of anesthetic drugs are not good predictors of movement in response to a surgical stimulus because the main site of action for anesthetic drugs to prevent movement is the spinal cord. The use of depth-of-anesthesia monitoring in children is not as well understood as in adults. Several monitoring devices are commercially available. The BIS monitor is the most thoroughly studied and most widely used, but the amount of information about other monitors is growing. In the future, depth-of anesthesia monitoring will probably help in further refining and better understanding the process of administering anesthesia. PMID- 17342966 TI - Perioperative thermoregulation and temperature monitoring. AB - Traditionally, hypothermia has been thought of and used perioperatively as a presumptive strategy to reduce cerebral and myocardial tissue sensitivity to ischemia. Evidence, however, is mounting that maintenance of perioperative normothermia is associated with improved outcomes in patients undergoing all types of surgery, even cardiac surgery. Ambient environmental temperature is sensed by free nerve endings in the dermal and epidermal layers of the skin, which are the axonal extensions of thermosensitive neurons found in the dorsal root ganglia. Free nerve endings in the skin, by means of transient receptor ion channels that are specifically thermosensitive, also may directly sense environmental temperature. This information is transmitted to the preoptic/anterior hypothalamic region of the brainstem, which coordinates efferent responses to abnormal temperature deviation. People have evolved a highly integrated thermoregulatory system that maintains core body temperature in a relatively narrow temperature range. This system, though, is impaired by the stress of regional and general anesthesia, and the added exposure that occurs during the surgical procedure. When combined, these factors can lead to unwanted thermal disturbances. In a cold operating room environment, hypothermia is the usual perioperative consequence; however, hyperthermia is more dangerous and demands immediate diagnosis. Intraoperative hypothermia usually develops in three phases. The first is a rapid decrease in core temperature following anesthetic induction, which mostly results from redistribution of heat from the core thermal compartment to the outer shell of the body. This is followed by a slower, linear reduction in the core temperature that may last several hours. Finally, a core temperature plateau is reached, after which core temperature remains virtually unchanged for the remainder of the procedure. The plateau can be passive or result from re-emergence of thermoregulatory control in patients becoming sufficiently hypothermic. Mild hypothermia in the perioperative period has been associated with adverse outcomes, including impaired drug metabolism, prolonged recovery from anesthesia, cardiac morbidity, coagulopathy, wound infections, and postoperative shivering. Perioperative temperature monitoring devices vary by transducer type and site monitored. More important than the specific device is the site of temperature monitoring. Sites that are accessible during surgery and give an accurate reflection of core temperature include esophageal, nasopharynx, bladder, and rectal sites. Core temperature also may be estimated reasonably using axillary temperature probes except under extreme thermal conditions. Rather than taking a passive approach to thermal management, anesthesiologists need to be proactive in monitoring patients in cold operating rooms and use available technology to prevent gross disturbances in the core temperature. Various methods are available to achieve this. Prewarming patients reduces redistribution hypothermia and is an effective strategy for maintaining intraoperative normothermia. Additionally, forced-air warming and circulating water garments also have been shown to be effective. Heating intravenous fluids does not warm patients, but does prevent fluid-induced hypothermia in patients given large volumes of fluid. This article examined the evolutionary adaptations people possess to combat inadvertent hypothermia and hyperthermia. Because thermal disturbances are associated with severe consequences, the standard of care is to monitor temperature during general anesthesia and to maintain normothermia unless otherwise specifically indicated. PMID- 17342967 TI - Coagulation monitoring. AB - Monitoring hemostasis is now possible by different modalities, of which the point of care devices seem most helpful to the clinician in the operating room. Most of these monitors are being used in the cardiac population, and their significance in other fields remains to be assessed. PMID- 17342968 TI - Monitoring hepatic and renal function. AB - Liver disease represents a serious risk factor for patients requiring anesthesia and surgery. Even subclinical liver disease increases perioperative morbidity and mortality. Perioperative renal dysfunction and failure have similar implications. Thus, detection of early hepatic and renal dysfunction and monitoring of their progress is essential. This article discusses methods for monitoring hepatic and renal function in patients who have high risk for liver or renal injury in the perioperative period. PMID- 17342969 TI - Obtaining leadership support for medical safety programs: a practical approach. PMID- 17342971 TI - Underdeveloped infection control in ambulatory care: impact of an infection control program in primary care centers. PMID- 17342970 TI - Electrocardiograph-based emergency department risk management tool based on the ACI-TIPI: potential impact on care and malpractice claims. PMID- 17342972 TI - Fraud and abuse: scheme may be criminal violation if 'one purpose' is to induce referrals. United States v. LaHue, F.3d, Nos 99-344, 99-347, 99-352 (10th Cir. June 18, 2001). PMID- 17342973 TI - Discrimination: a cause of action for harassment under the ADA. Flowers v. Southern Regional Physician Services, Inc., 247 F.3d 229 (5th Cir. 2001). PMID- 17342974 TI - Ostensible agency: hospital may be liable for actions of physician's independent physician. Goldberg v. Isdaner, 2001 PA Super. 180 (Pa. Super. 2001). PMID- 17342975 TI - Staff privileges: revocation of staff privileges in retaliation for whistleblowing is improper. Clark v. Columbia/HCA Information Services, Inc., 25 P.3d 215 (Nev. 2001). PMID- 17342976 TI - Physician stress management: a new approach to reducing medical errors and liability risk. PMID- 17342977 TI - Shoulder dystocia and fundal pressure: a medical legal dilemma. PMID- 17342978 TI - Potential for risk reduction through ISO 9000-based redesign of emergency triage. PMID- 17342979 TI - Leverage and the hard hospital professional market. PMID- 17342980 TI - Risk management: risk managers need to be political animals. Craven v. University of Colorado Hospital Authority, 260 F. 3d. 1218 (10th Cir. 2001). PMID- 17342981 TI - Sexual harassment: single severe incident can show a hostile environment. Turnbull v. Topeka State Hospital, 255 F. 3d 1238 (10th Cir. 2001). PMID- 17342982 TI - Medical information: cause of action exists for disclosure of medical information. Berger v. Sonneland, 144 Wash. 2d 91, 26 P. 3d 257 (Wash. 2001). PMID- 17342983 TI - Medical staff issues: procedural due process sufficient for HCQIA immunity. Meyer v. Sunrise Hospital, 22 P. 3d 1142 (Nev. 2001). PMID- 17342984 TI - Professional liability: no duty to prevent unforseeable suicide. Lawlor v. Orlando, 795 So. 2d 147 (Ct. App. Fla. 2001). PMID- 17342985 TI - Advance directives: clear and convincing evidence of wish to terminate treatment may be required. Conservatorship of Wendland, 26 Cal. 4th 519, 28 P. 3rd 151, 110 Cal. Rptr. 2nd 412 (Cal. 2001). PMID- 17342986 TI - The case favoring wrong-site labeling. PMID- 17342987 TI - Strategies and tips for maximizing failure mode and effect analysis in an organization. PMID- 17342988 TI - Facing workplace violence in the health care industry. PMID- 17342989 TI - Emergency medicine: EMTALA liability ends with admission. Bryant v. Adventist Health System/West, 289 F. 3d 1162 (9th Cir. 2002). PMID- 17342990 TI - Informed consent: hospital may have duty to obtain informed consent. Rogers v. T.J. Samson Community Hospital, 276 F. 3d 228 (6th Cir. 2002). PMID- 17342991 TI - Medical malpractice: Good Samaritan protection may be difficult to obtain in Texas. Ramirez v. McIntyre, 59 S. 3d 821 (Ct. App. Tex. 2001). PMID- 17342992 TI - [Multicentered, randomized, controlled clinical trial on patients with IgA nephropathy of Qi-yin deficiency syndrome type]. AB - OBJECTIVE: To evaluate the effect and safety of Chinese medicine Compound Shenhua Tablet (SHT) on IgA nephropathy patients of TCM Qi-yin deficiency syndrome type, by using angiotensin-converting enzyme inhibitors (ACEI) fosinopril as the positive control. METHODS: Adopting prospective, multicentered, double-blinded, double-dummy, randomized, controlled trial design, 131 patients with IgA nephropathy of Qi-yin deficiency syndrome type were assigned to two groups, the 65 patients in the treated group (SHG) and the 66 in the control group treated with SHT and fosinopril respectively for 12 weeks. The indexes of efficacy, including TCM syndrome scores, urinary protein, serum creatinine, urea nitrogen and endogenous creatinine clearance rate, as well as the indexes of safety, including liver function and occurrence of adverse events were observed. RESULTS: There was no significant statistical difference between the two groups in aspects of baseline demographic characteristics and clinical figures, including gross hematuria, hypertension, incidence of renal insufficiency, total course of disease, urinary protein, TCM syndrome score, renal pathological Katafuchi score, glomerular score, tubular-interstitial score, vascular score and Lee grading. Afte 12 weeks of treatment, the content of 24-h urinary protein significantly decreased by 0.26 +/- 0.95 g/24 h and 0.26 + 0.92 g/24 h respectively in the two groups, showing significant difference in comparing with baseline, but insignificant difference between the two groups (P > 0.05); the scores of TCM dominant syndromes in them decreased by 2.52 +/- 2.34 scores and 1.74 +/- 2.12 scores respectively with significant difference as compared with baseline (P < 0.01), and in comparison between groups (P < 0.05). No significant change in levels of serum creatinine, urea nitrogen, endogenous creatinine clearance rate in both groups was found (P > 0.05). Scores of TCM accompanied syndromes in the two groups was significantly decreased (P < 0.01), but the difference between them was insignificant (P > 0.05). No severe adverse event occurred during treatment, and the occurrence in the two groups was similar. CONCLUSION: SHT, just like the positive control medicine fosinopril, can effectively decrease the proteinuria and improve clinical syndrome of IgA nephropathy patients of Qi-yin deficiency syndrome type, and shows no serious adverse reaction. PMID- 17342993 TI - [Effect of hemodialysis with Chinese herbs of supplementing qi and activating blood circulation on platelet membranous glycoprotein CD62P in patients with chronic renal failure]. AB - OBJECTIVE: To explore the effects of dialysate contained Chinese herbs for replenishing qi and activating blood circulation on platelet membranous glycoprotein CD62P in patients with chronic renal failure (CRF) undergoing hemodialysis. METHODS: Forty patients underwent maintaining hemodialysis were randomly assigned to two groups, the Western medicated group (WMG) and the Chinese herbs group (CHG). The content of CD62P in all patients was detected by ELISA before and after hemodialysis. RESULTS: The levels of blood urea nitrogen, creatinine, potassium, hematocrit, platelet count and carbon dioxide combining power (CO2CP) as well as the expression of CD62P after treatment were significantly changed in both groups with significant difference as compared with those before treatment (both P < 0.05). And comparison between the two groups in expression of CD62P after treatment also showed significant difference (P < 0.05). But the improvement in TCM syndrome between the two groups was insignificantly different (P > 0.05). CONCLUSION: Hemodialysis with dialysate containing Chinese herbs of replenishing qi and activating blood circulation can decrease the expression of platelet membranous glycoprotein CD62P, which may be associated with the mechanism of Chinese herbs in treating CRF. PMID- 17342994 TI - [Clinical study of Reinhartdt and sea cucumber capsule combined with donepezil in treating Alzheimer's disease]. AB - OBJECTIVE: To study the efficacy and safety of Reinhartdt and sea cucumber capsule (RSC) combined with donepezil in treating Alzheimer's disease (AD), and its effect on thyroid function axis. METHODS: Sixty-eight patients were randomly assigned to the RSC group, the Donepezil group and the combined treatment group, who were treated for 3 and 6 months with RSC, Donepezil and RSC combined with Donepezil, respectively. The curative effect was evaluated by scoring according to Mini-Mental State Examination (MMSE), ADAS-Cog and ADL chart, and the level of thyroid hormones, including TSH, FT3, FT4, TT3 and TT4, were measured with radioimmunoassay before treatment, 3 and 6 months after treatment respectively. RESULTS: As compared with the baseline, MMSE score increased, ADAS-Cog score and ADL score decreased significantly in all the three groups after 3 months and 6 months of treatment (P < 0.05 and P < 0.01), but the improvement in the combined treatment group was more significant than that in the other two groups (P < 0.01). After 6 months of treatment, the levels of FT3 and FT4 in the combined treatment group were significantly changed (P < 0.01), but no significant change in all the thyroid hormones was found in the other two groups. No obvious adverse reaction occurred in all the three groups. CONCLUSION: RSC combined with Donepezil in treating AD is effective and safe with no evident adverse reaction, better than single drug treatment, which may be through influencing the metabolism of thyroid hormones to improve the cognition function of AD patients. PMID- 17342996 TI - [Epidemiological survey on etiology of Gan-qi inversion syndrome and Gan-qi stagnation syndrome and study on the evocative mode of emotional diseases]. AB - OBJECTIVE: To investigate the etiology of Gan-qi inversion syndrome and Gan-qi stagnation syndrome, and to study the evocative mode of emotional diseases. METHODS: One thousand and twenty-six subjects, engaged as workers, cadres, teachers and farmers, come from Qingdao City, Jinan City and Qingyun County were surveyed adopting the on-spot investigation. RESULTS: The percentage of patients with Gan-qi inversion or stagnation syndrome caused by emotional internal injury was 53.9%; the emotional stimulations were primary the angry with compunction and the gloomy angry with grievance, secondly the unacquirable wishes, anxiety and grief. CONCLUSION: Emotional stimulation is the main cause of Gan-qi inversion or stagnation syndromes, cross actions of several emotional factors directly impairing Gan is the main evocative mode of emotional diseases. PMID- 17342995 TI - [Clinical study on Tangweikang in treating diabetic gastroparesis]. AB - OBJECTIVE: To investigate clinical effects and mechanism of Tangweikang (TWK) in treating diabetic gastroparesis. METHODS: Ninety diabetic gastroparesis patients were randomly assigned to 3 groups. Besides conventional hypoglycemic treatment, the 30 patients in the treated group were given TWK and the 30 in the control group were given Domperidone additionally, while to the 30 in the blank group, no additional drug was given. The clinical efficacy and the changes in level of motilin and gastric emptying rate were observed. RESULTS: TWK showed significant effects in improving clinical symptoms of patients, increasing gastric emptying rate, promoting gastrointestinal kinetics, shortening gastric emptying time and was beneficial to the control of blood sugar, including the 2 h post-prandial blood sugar and fructosamine. The curative rate and total effective rate in the treated group were 63.33% (19/30) and 93.33% (29/30) respectively, significantly different to those in the control group 26.67% (8/30) and 63.33%, also different to those in the blank group 23.33% (3/ 30) and 10.00%, respectively (P < 0.01). The clinical efficacy in the treated group was superior to that in the other two groups. CONCLUSION: TWK has favorable therapeutic efficacy in treating DGP. PMID- 17342997 TI - [Effect of Chinese herbs for tonifying Shen on balance of Th1 /Th2 in children with asthma in remission stage]. AB - OBJECTIVE: To explore the molecular mechanism of Chinese herbs for tonifying Shen on asthma by adjusting the imbalance of Th1/Th2. METHODS: Peripheral blood mononuclear cells (PBMC) separated from anticoagulated venous blood of 20 children with asthma in remission stage (3 ml from each) were equally divided into three groups, the blank group and the Chuankezhi (CKZ) groups cultured with media without or with CKZ of different concentrations respectively, for 48 h in vitro. The mRNA expressions of T-bet, GATA-3, IFN-gamma and IL-4 in the sediment collected from the cultures were measured by real-time fluorescence quantitative polymerase chain reaction technology. RESULTS: As compared with those in the blank group, in the CKZ groups, T-bet mRNA expression and IFN-gamma mRNA expression were significantly higher, especially in CKZ II group (P < 0.01 and P < 0.05 resepectively); GATA-3 mRNA expression was insignificantly different (P > 0.05); IL-4 mRNA expression was significantly lower (P < 0.01). Moreover, the ratios of T-bet/GATA-3 and IFN-gamma/IL-4 were higher in the CKZ groups than those in the blank group, respectively, though showing insignificant difference in the former (P > 0.05), the difference in the latter was certainly significant (P < 0.05). CONCLUSION: Chinese herbs for tonifying Shen can adjust the imbalance of Th1/Th2 in multiple layers by enhancing the function of Th1 cells and attenuating the function of Th2 cells, which may be realized through various links as regulating the expression of transcription factors and cytokines. PMID- 17342998 TI - [Comparative study on treatment of somnipathy in patients with hypertension by traditional Chinese medicine and by estazolam]. AB - OBJECTIVE: To study the efficacy of traditional Chinese medicine (TCM) in treating somnipathy in patients with hypertension, and to observe the change of blood pressure after sleep being improved. METHODS: Two hundred and thirty-nine patients with hypertension accompanied somnipathy were randomly assigned to two groups, 123 patients in the treated group were treated with TCM according to syndrome differentiation, and 116 in the control group treated with Estazolam. Changes of blood pressure, scores of sleep dysfunction rating scale (SDRS), Hamilton anxiety rating scale (HAMA) and treatment emergent symptom scale (TESS) before and after treatment were observed. RESULTS: TCM showed a significant effect on hypnagogic disturbance, and significantly reduced the scores of insomnia syndromes in early sleep stage, improve the quality of sleep, prolong the sleeping time to fulfill the physiological requirement, the total effective rate being 80.5% (99/123 cases), with the overall effect higher than that (66.4%, 77/116 cases) in the control group (P < 0.05). Along with the improving of sleep, blood pressure, both systolic and diastolic, reduced in both groups, but with the reduction in the treated group superior to that in the control group (P < 0.01), and the rate of reaching target BP (< 140/90 mmHg) in the former was also significantly higher than that in the latter (39.7%, 46/116 cases, P < 0.05). As compared with those in the control group, the occurence of adverse reaction, were less in the treated group (P < 0.05). CONCLUSION: TCM has better efficacy in treating somnipathy of hypertension patients than Estazolam. And the improvement of somnipathy is favorable for improving the hypertensive condition of patient. PMID- 17342999 TI - [Study on the relationship between vascular endothelial growth factor and syndrome type of traditional Chinese medicine in patients with gastric carcinoma]. AB - OBJECTIVE: By detecting the expression of vascular endothelial growth factor (VEGF) in different syndrome types of traditional Chinese medicine (TCM) in patients with gastric carcinoma (GC) to investigate the correlation of VEGF and TCM syndrome type for exploring the internal relationship between disease and syndrome. METHODS: The correlated clinical manifestations were recorded in detail and patient's syndrome type was differentiated at beside before operation. After operation, pathological examination on the resected specimen was performed routinely. The expression of VEGF in 104 GC patients of three different syndrome types, i.e. Pi-Wei asthenia type (type 1), Gan-Wei disharmony type (type 2) and phlegm-stasis-poisons stagnant type (type 3)and in 30 patients with superficial gastritis (for control) were determined by immunohistochemical method. The expressions of VEGF in different syndrome types were analyzed by combining with correlated clinical pathological characteristics. RESULTS: (1) The VEGF protein positive expression rate in GC patients was 81.7% (85/104), it was significantly higher than that in the control group with positive rate being zero (P < 0.01). (2) The intensity of VEGF expression was positively correlated with the depth of tumor infiltration, the extent of lymph node metastasis and the pathological staging of cancer (P < 0.01), and showed no evident correlation with the size of tumor and its degree of cell differentiation (P > 0.05). (3) Levels of VEGF expression in various syndrome types were significantly different (P < 0.01), the highest expression showed in the type 3, the second in the type 2, and the lowest in the type 1, comparison between them all showed significant difference (P < 0.01 for 3 vs 1, P < 0.05 for 3 vs 2 and 2 vs 1). CONCLUSION: (1) VEGF could be taken as an index for evaluating the infiltration, metastasis and prognosis of GC. (2) The different expressions of VEGF play different roles in the GC metastatic process of patients of different syndrome types, and the pathogenesis of GC metastasis may be probably various in different syndrome types. VEGF is the relevant gene of GC of type 2 and type 3. (3) High VEGF expression shows positive correlation with the GC metastasis of type 2 and 3, suggesting that the higher the intensity of evil excess, the more possibilities of tumor infiltration and metastasis and the worse the prognoses will be. PMID- 17343000 TI - [Influence of different endothelial cells conditioned medium on the function of mitochondria of cortical neurons and the protective effect of Tongluo Jiunao Injection]. AB - OBJECTIVE: To study the influence of conditioned medium of rat brain microvascular endothelial cells on mitochondrial function of cortical neurons and the protective effect of Tongluo Jiunao Injection (TJI) on it. METHODS: Four kinds of conditioned endothelial cell (EC) cultured medium were prepared, i.e. the N-CM medium prepared by EC cultured in the normal conditioned medium without any treatment; the NT-CM prepared by EC cultured in N-CM and treated with TJI 1 microl/ml for 10 h; the I-CM prepared by EC cultured in the non-glucose kreb medium under hypoxia condition; and the IT-CM by EC pre-treatce with TJI 1 microl/ml for 4 h and cultured as that of I-CM. The levels of neuronic mitochondrial activity, membrane potential (MMP) and cytochrome C (Cyt C) were determined before and after the glucose-oxygen deprived model neurons of brain cortex being cultured with different kinds of conditioned EC cultured medium for assessing the effects of these media on mitochondria of injured neuron. RESULTS: As compared with those of the normal neuron, the mitochondrial activity and MMP of all injured neurons decreased and Cyt C level increased significantly. But comparison of these indexes among neurons cultured with different conditioned EC culture media showed that the greatest extent abnormality revealed in the N-CM cultured neurons, which even greater than that in the model neuron; while that was less in the N-CM cutured neuron than in model neuron; as for those cultured in the NT-CM and IT-CM, i.e. the TJI treated cuture medium, the abnormal changes were reduced significantly when compared with those cultured in medium untreated with TJI (N-CM and I-CM), respectively (all P < 0.05). CONCLUSION: The paracrine secretion of the brain microvascular endothelial cells has evident regulatory effect on survival of the injured neurons, which might possibly be related to its protective effect on neuron mitochondrial function, and TJI could enhance the protective effect. PMID- 17343001 TI - [Comparison of gene expression profiles between rats of Shen deficiency syndrome and Shen-yang deficiency syndrome differentiated according to therapeutic efficacy of drugs used]. AB - OBJECTIVE: To explore similarity and difference of connotation between Shen deficiency syndrome (SDS) and Shen-yang deficiency syndrome (SYDS) on the molecular level. METHODS: The senescent SD rats and corticosterone-treated rats were adopted for models of SDS and SYDS respectively, their syndrome was differentiated according to the therapeutic efficacy of treatment with epimedium flavonoids (EF). The gene expression profiles of hypothalamas, pituitary, adrenal gland and lymphocytes (HPAT axis) were detected before and after EF treatment using gene chip provided by Affymetrix company. RESULTS: As compared with the young rats, the ageing rats and corticosterone-treated rats showed a significant down-regulation in highly consistent pattern, of various neurotransmitters of HPAT axis firstly, followed with that of growth and sex hormone related genes. EF could reverse the above genes expression in both models, and for SYDS model rats, it could also significantly up-regulate the gene expressions of heat shock protein, cytochrome P450 and thyroid stimulating hormone (TSH). CONCLUSION: Both SDS and SYDS model rats show connotation of Shen deficiency, and the substantial base of Shen-yang deficiency syndrome resides in the process of oxidative phosphorylation of energy metabolism accelerated by thyroid hormone. PMID- 17343003 TI - [Effect of Qingdu Suppository-containing serum on cervical carcinoma SiHa cell MDM2 gene expression]. AB - OBJECTIVE: To investigate the effect and mechanism of Qingdu Suppository (QDS) in suppressing the growth of SiHa cell of cervical carcinoma on the cytobiologic and molecular biologic level. METHODS: SiHa cells were cultured in media with serum containing different concentrations of QDS and blank serum, as well as serum containing various Chinese herbal or Western drugs as positive control. SiHa cell growth and proliferation was determined by MTT assay, the cell cycle and apoptosis were analyzed by flow cytometry technique, and the expression of proto oncogene MDM2 detected semi-quantitatively by RT-PCR. RESULTS: The amount of cells decreased after cultured with drug-containing serum 8% in concentration, with the highest inhibitory effect shown by drug-containing serum after acting for 72 h, which was significantly different to that in the control group (P < 0.01). Among the various time phases of cell cycle, the percentage of cells in S phase was significantly decreased. Drug-containing serum showed somewhat effect on cell apoptosis, but no obvious regularity could be found. RT-PCR showed significant decrease of MDM2 expression. CONCLUSION: QDS containing serum could not only directly suppress the growth of cervical carcinoma cells, but also inhibit the tumor by the molecular mechanism of down-regulating MDM2 gene expression. PMID- 17343002 TI - [Study on Yiqi Huayu Bushen Recipe and its disassembled recipes in regulating mRNA expression of collagens and metabolic enzymes in extracellular matrix of cervical disc]. AB - OBJECTIVE: To study the effects of Yiqi Huayu Bushen Recipe (YHBR) and its disassembled recipes on mRNA expressions of collagen I, III, X, matrix metalloproteinase (MMPs) and tissue inhibitor of metalloproteinase (TIMP) in extracellular matrix of cervical disc in model rats of cervical vertebral disc degeneration. METHODS: The mRNA expressions of collagens, MMP-13 and TIMP-1 were detected by RT-PCR. The strips were scanned by gel imaging system scanner, and the optical density was autocalculated by computer. RESULTS: Compared with those of the sham-operative group, the mRNA expressions of collagen I , Ill and X and MMP-13 of the model rats increased markedly (P < 0.01), which were lowered by YHBR and its disassembled recipes (P < 0.01 or P < 0.05), and the levels after YHBR treatment were significantly different to those after Western medicine treatment. However, no remarkable change was found in TIMP-1 mRNA expression in the model rats (P > 0.05). CONCLUSION: In the degenerated intervertebral disc the mRNA expressions of collagen I , III, X and MMP-13 increased, TIMP-1 mRNA expression decreased and the proportion of MMPs/TIMP was in imbalance. YHBR and its disassembled recipes could postpone the degeneration of intervertebral disc through regulating mRNA expressions of collagens and their correlated metabolic enzymes. PMID- 17343004 TI - [Effects of Ginkgo biloba extract 50 on hypoxia induced endothelial dysfunction]. AB - OBJECTIVE: To preliminarily investigate the influence of hypoxia on human umbilical vein endothelial cells (HUVECs), and the effect of Ginkgo biloba extract 50 (GBE50) on it. METHODS: Flow cytometry, TUNEL, RT-PCR, Western blot, etc. were applied, to study the effect of hypoxia and GBE50 on endothelial cells. RESULTS: After being interfered by hypoxia for 24 h, the levels of reactive oxygen species (ROS) in HUVECs and the apoptotic rate either in the early or in the late stage significantly increased, and accompanied with the increased levels of endothelin-1 mRNA (ET-1) and endothelial oxide synthase (eNOS) protein. However, when HUVECs were pretreated with GBE50 (25 [microg/ml) 4 h before hypoxia, the apoptotic rate in the early or late stage and expression of ET-1 mRNA significantly decreased (P < 0.05), and the heightened ROS level and eNOS expression partially decreased (P > 0.05). CONCLUSION: Hypoxia can induce endothelial dysfunction, which could be partially or significantly reversed by GBE50, it shows a certain protective effect on hypoxia induced endothelial dysfunction. PMID- 17343005 TI - [Clinical observation on treatment of melancholia by acupuncture following principle of relieving depression and regulating mentality]. AB - OBJECTIVE: To observe the curative effect of acupuncture following principle of relieving depression and regulating mentality (RDRM) in treating patients with melancholia, and compare it with that of Western medicinal treatment. METHODS: Patients in the observed group were treated with needling and electroacupuncture (EA), and those in the control group orally taken Fluoxetine or Paroxetine. The curative effect, Hamilton Depression Scale scores (HAMD), effect initiating time and sustaining time were observed and compared. RESULTS: The total effective rate was 87.5% and 79.1% in the observed group and the control group respectively, showing insignificant difference between them (P > 0.05), but comparison of the initiating time and sustaining time between the two groups did show significant different (P < 0.01). CONCLUSION: Acupuncture with following RDRM principle has definite effect in treating melancholia, which is comparable to Western medicinal treatment, and shows a superiority to the latter in effect initiating and sustaining time. PMID- 17343006 TI - [Effect of Fructus Bruceae oil emulsion on cellular immune function and quality of life in patients with non-small cell lung cancer]. AB - OBJECTIVE: To observe the effect of Fructus Bruceae oil emulsion (FBE) on cellular immune function (CIF) and quality of life (QOF) in patients with non small cell lung cancer (NSCLC) after chemotherapy. METHODS: One hundred and fifteen patients with mid-late stage NSCLC were randomly assigned to two groups, the 57 patients in the control group were only treated with chemotherapy of GP regimen, 58 in the treatment group with the chemotherapy of the same regimen and combined with FBE. The clinical efficacy was evaluated after two cycles of chemotherapy. RESULTS: The effective rate was 51.8% and 47.4% in the treatment group and the control group respectively, the difference between them was insignificant (P > 0.05). CIF and QOF in the treatment group were better than those in the control group after chemotherapy respectively (P < 0.01), in the latter, CIF and QOF were desreased after chemotherapy (P < 0.05). CONCLUSION: FBE combined with chemotherapy can improve the cellular immune function and quality of life in patients with mid-late stage NSCLC. PMID- 17343007 TI - [Effect of Panax notoginseng saponins on serum neuronal specific enolase and rehabilitation in patients with cerebral hemorrhage]. AB - OBJECTIVE: To observe the effect of Panax notoginseng saponins (PNS) on serum content of neuronal specific enolase (NSE) and function recovery in patients with cerebral hemorrhage (CH) for exploring the therapeutic action of PNS in treating CH. METHODS: Fifty CH patients with their course of disease not more than 5 days were randomly assigned to two groups, 27 in the PNS group and 23 in the control group, all were treated with conventional treatment, while PNS was given additionally to the PNS group. The serum levels of NSE before and after treatment were determined by electrochemiluminescence, and the recovery of patients, including their neuro-function deficit and daily living activity, was assessed according to scoring by the National Institute of Health Stroke Scale (NIHSS) and Barthel Index (BI) respectively. RESULTS: Before treatment, the difference between the two groups in serum NSE content and scores of NIHSS and BI was insignificant (P > 0.05). However, after 3 weeks of treatment, the level of NSE and score of NIHSS were significantly lower, while score of BI was significantly higher in the PNS group than those in the control group respectively (all P < 0.01). In the PNS group, the level of NSE showed a positive correlation with the score of NIHSS (r = 0.757, P < 0.05), and a negative correlation with the score of BI (r = - 0.803, P < 0.05). CONCLUSION: PNS can effectively protect the neuron and promote functional rehabilitation in patients after CH. PMID- 17343008 TI - [Yiqi Huoxue Recipe combined with polyene phosphatidycholine capsule in treating 50 patients with non-alcoholic fatty hepatitis]. AB - OBJECTIVE: To observe the clinical effect of Yiqi Huoxue Recipe (YHR) combined with polyene phosphatidycholine capsule (PPC) in treating non-alcoholic fatty hepatitis (NFH). METHODS: Eighty NFH patients were randomly assigned to two groups according to the sequence of their visiting, the 30 in the control group were treated with PPC alone and the 50 in the treated group were given YHR and PPC in combination. The therapeutic course for both groups was 3 months. RESULTS: The improvement of syndrome, liver function, blood lipid and B ultrasonic figure in the treated group was superior to that in the control group, and the clinical efficacies between the two groups were significantly different (P < 0.01). CONCLUSION: YHR combined with PPC has a good effect in treating NFH. PMID- 17343009 TI - [Key points of protocol design on clinical therapeutic research of traditional Chinese medicine]. AB - Therapeutic effect is the core in clinic medicine. Traditional Chinese medicine (TCM) has certain advantages on clinical efficacy, but is still lack of reliable evidence. With the rapid development of evidence based medicine (EBM), more and more attention is paid on scientific evaluation of clinical efficacy increasingly. To carry out TCM clinical therapeutic research and to scientifically evaluate its efficacy has become a very important task for TCM development. Scientific and precise protocol design is the precondition for progressing the research and obtaining high quality evidences. The article puts stress on how to design the clinical therapeutic program of research on TCM in combining with characteristics of TCM. PMID- 17343010 TI - [Exploration on health concept of TCM and the operationalization of its measurement]. AB - Viewing from the concept of health and several basic characteristics of health outlook of traditional Chinese medicine (TCM), assimilating the thinking and procedure of modern scientific research concerning operationalization, in this paper, the TCM concept of health and its measurement operationalization as well as their relevant things were expounded. And the frame, related domain, indexes and items of health assessment scale based upon TCM theory were tried to be established using opertionalization method. PMID- 17343011 TI - [Progress of study on action mechanisms of TCM in anti-tumor and preventing metastasis of tumor]. AB - In this article, the literatures concerning the mechanism of TCM in anti-tumor and tumor metastasis prevention in recent years were reviewed and summarized into categories of effective components, effective portion, extraction of single drug, and TCM compound. PMID- 17343012 TI - [Progress of study on prevention and treatment of xeloda induced hand-foot syndrome by measures of Chinese and Western medicine]. AB - In this article, the mechanism of hand-foot syndrome (HFS) and its prevention and treatment measures with Chinese and modern medicine in recent years were reviewed. Although standard preventive and therapeutic program on HFS is still lack so far, both TCM and modern medicine have achieved certain effects in this aspect, which is of important significance for improving the quality of life and the effect of chemotherapy in patients with HFS. PMID- 17343013 TI - International standards of tuberculosis care. PMID- 17343014 TI - Access to condoms for female sex workers in Andhra Pradesh. AB - BACKGROUND: Condoms are an essential part of comprehensive HIV prevention and care programmes. We report the accessibility of male condoms for female sex workers (FSWs) and the associated characteristics that may play a major role in determining access to condoms for FSWs. METHODS: Confidential interviews of 6509 street- and home-based FSWs in 13 districts of the Indian state of Andhra Pradesh provided data on the number of paying clients and various aspects of access to free condoms and purchase of condoms. Access to condoms was defined as having ever obtained condoms either through free distribution or through purchase. Multivariate analyses were done separately for street- and home-based FSWs to describe correlates of their access to condoms. The requirement of condoms was assessed based on the number of paying clients during the past 15 days. RESULTS: Data on condom access were available for 6465 (99.3%) FSWs. A total of 2850 (44.1%; 95% CI: 36.2%-52.0%) reported accessing free condoms ever and 2336 (36.1%; 95% CI: 30.6%-41.6%) had purchased condoms ever (not mutually exclusive). The primary sources for condoms were non-governmental organization facilities (73.8%) and pharmacies (79.7%) for free and purchased condoms, respectively. A total of 3510 (54.3%; 95% CI: 48.5%-60.1%) FSWs reported no access to free or purchased condoms during the past 15 days, and this no access was significantly higher for those > 30 years of age, with no schooling, street-based FSWs, and with no participation in a FSW support group (p < 0.001 for each in univariate analysis). Participation in a FSW support group was the main predictor of access to free condoms for both types of FSWs during the past 15 days with multivariate analysis. Condom requirements during the past 15 days were met for 67.5% of FSWs who had accessed only free condoms and for 33.8% of those who had accessed only purchased condoms. CONCLUSIONS: One-fourth of FSWs had never accessed condoms, and a little over half of those who had ever accessed reported no access during the past 15 days. Condom requirements were not met for three-fifths of the FSWs. HIV prevention programmes need to Increase access to free condoms for FSWs in Andhra Pradesh as access to condoms is a necessary prerequisite for condom use. PMID- 17343015 TI - Corrosive-like strictures caused by ingestion of aluminium phosphide. AB - Aluminium phosphide ingestion is a major cause of poisoning-related mortality in tropical countries. Local oesophageal complications due to aluminium phosphide have been reported to occur rarely. We describe 3 patients who survived the intake of aluminium phosphide tablets and developed oesophageal strictures. PMID- 17343016 TI - Chikungunya epidemic: an Indian perspective. AB - Chikungunya, caused by the chikungunya virus, recently emerged as an important public health problem in the Indian Ocean Islands and India. In 2006, an estimated 1.38 million people across southern and central India developed symptomatic disease. The incidence of the disease may have been higher but may have been underreported due to lack of accurate reporting. First isolated in Tanzania in 1953, the chikungunya virus belongs to the family Togaviridae (single stranded RNA alphaviruses) and has 3 distinct genotypes: East African, West African and Asian. Previous outbreaks in India (1963 and 1973) were caused by the Asian genotypes, but the 2005 epidemic in the Indian Ocean islands and the 2006 epidemic in India have been attributed to the East African genotype. The virus is transmitted to humans by the bites of mosquitoes of the species Aedes aegypti and A. albopictus. Researchers speculate that mutation of the virus, absence of herd immunity, lack of vector control, and globalization of trade and travel might have contributed to the resurgence of the infection. Chikungunya is characterized by high fever, severe arthralgia and rash. Although viral diagnostics (culture, serological tests and polymerase chain reaction tests) can be used to confirm the infection, these tests are not accessible during outbreaks to the majority of the population. The disease is a self-limiting febrile illness and treatment is symptomatic. As no effective vaccine or antiviral drugs are available, mosquito control by evidence-based interventions is the most appropriate strategy to contain the epidemic and pre-empt future outbreaks. PMID- 17343017 TI - BCG immunization: is it really efficacious and cost-effective? PMID- 17343018 TI - Management of psychosis in primary care. PMID- 17343019 TI - Case detection rate targets under DOTS: the Indian experience. AB - The DOTS programme in India has been recognized as the fastest growing programme in the world. It currently covers more than 1 billion people (90% of the population). In spite of this rapid expansion, the programme has consistently achieved the global target of 85% cure rates. However, improvement in case detection rates has been slow, and the global target of 70% has been achieved only in the last few quarters. Public-private partnerships were initiated at the national and local level with the non-health public sector, corporate sector and non-governmental organizations, private practitioners and medical colleges. The partnerships have significantly contributed to the case detection rates in the country, especially the medical colleges, which have contributed up to 5%-15%. Some areas achieved case detection rates well above 70%. There is a need to forge new initiatives, strengthen existing partnerships and make special efforts to access the poorer, vulnerable and hard-to-reach sections of society more effectively. This would not only increase the numbers of cases but also serve the overarching objective of equity. Disaggregated targets should be set, with much higher ones for selected areas, sectors and institutions. PMID- 17343020 TI - The world: a different view. PMID- 17343021 TI - Patients referred from large public sector corporations: some experiences. PMID- 17343022 TI - Ministerial Annual Reviews of NHS boards. PMID- 17343023 TI - 'Exercising' but not active: implications for physical activity counselling. PMID- 17343024 TI - Attitude, concerns and conduct of research among medical students. PMID- 17343025 TI - Structure of Collagen. 1954, 1955. PMID- 17343026 TI - Growth of hospital-based palliative care programs surges. AB - Palliative care programs can improve quality of care for seriously ill patients in hospitals. Facility notes shortened lengths of stay, improved patient satisfaction. Multidisciplinary teams have greatest success; coordination of care critical. PMID- 17343027 TI - Study shows link between safety and satisfaction. AB - Focus on patient satisfaction does not come at the detriment of focus on safety. Patients notice staff safe practices, such as using computers for prescriptions or washing hands. Hospitals that show transparency are more able to overcome challenges in patient satisfaction. PMID- 17343028 TI - VHA initiates regional RRT collaborative program. AB - Twelve of 188 facilities in Western region earn recognition for high-level performance. Efforts supported with face-to-face and satellite sessions, e-mail, and phone conferences. Programs seek to empower anyone to initiate team call- even patients and family members. PMID- 17343029 TI - Patients view errors more broadly than clinicians. AB - Patients' definition of medical errors include staff not communicating effectively, or not being responsive to patient requests. While 94% of patients believed their medical safety had been good to excellent, 39% experienced at least one error-related concern. "Perception gap" can have a significant impact on efforts to improve patient safety. PMID- 17343030 TI - Balance Center aims to prevent falls. AB - Falls are the leading cause of injury deaths and the most common cause of nonfatal injuries and hospital admissions for trauma among adults 65 years and older. Center is response to physician requests for referrals of patients with balance problems. Hospital's standard nursing assessment includes grading patients on whether they may be a fall risk. PMID- 17343031 TI - [End-stage renal insufficiency concerns the cardiologist]. PMID- 17343032 TI - [Contrast media and percutaneous coronary interventions]. AB - Contrast media are widely used for percutaneous coronary interventions. Currently, about a dozen types of contrast media are available in France. On account of their overall safety, only low osmolar and isosmolar contrast media are used in practice. However, the appropriate use of contrast media remains difficult as accurate recommendations are lacking. Several doubts are still present regarding potential adverse effects of contrast media. Our review summarizes contrast media-related risks (hypersensitivity, arrhythmic risk, effects on coagulation and platelets, contrast media-induced nephrotoxicity) underlying mechanisms, prophylaxis strategies, and differences among contrast media. Many questions remain in this area and we need further prospective randomised trials. PMID- 17343033 TI - [Coronary artery disease and coronary angioplasty in chronic hemodialysis patients]. AB - Chronic renal insufficiency leads to many cardiovascular complications and provide worst prognosis, especially when patients need hemodialysis. The atherosclerosis of chronic hemodialysis patients is qualified as "accelerated" by some authors, because of a very fast and large progression. To improve prognosis, it seems to be very important to detect and treat the frequent and serious underlying cardiovascular disease. Because of the high rate of diabetes mellitus, silent ischemia is a very frequent clinical situation. In the other hand, coronary artery disease in chronic hemodialysis patients is frequently complex, with a large coronary extension and high rate of coronary calcifications. Consequently, this disease needs a specific therapeutic approach. Even though, percutaneous coronary interventions (PCI) are more complex in this population, it provides good results, and improves patient's prognosis. However, the rate of complications of the vascular approach and the rate of restenosis is high. New devices, such as Drug Eluting Stents (DES) can critically decrease restenosis rate, and closure devices for trans-femoral approach, provides very encouraging results in this high risk population. Despite, good results of PCI with DES use, the mortality is still high in this population. To improve our efficiency, we have to progress in our therapeutic strategies and optimize medical approach to treat the important biological perturbations. PMID- 17343034 TI - [Medical liability and coronary artery diseases]. AB - Until recently, for many people dying from a myocardial infarction was an inevitable fate. Myocardial infarction mortality rates have decreased drastically. At the same time, stents have clearly secured coronary angioplasties, removing the problems linked to coronary dissections such as abrupt closure or emergency coronary bypass. The iatrogenic risks have increased on account of the use of sophisticated techniques, powerful medications or the treatment of older patients. On the one hand, the media have informed people about the tremendous improvements in cardiology, however, on the other hand they have also given them over-optimistic expectations leading to an increase in the number of physicians sued. Now, physicians have to master ever more complex parameters such as new examination techniques prescriptions and interpretation (CT-scanner, MRI) and new medications. In order to prevent lawsuits, physicians should educate and inform their patients. To increase their chances in case of a lawsuit, physicians should improve the traceability of the treatment prescribed and information given to patients, but also make patients assume their responsibilities when they are reluctant to follow medical advices or treatments. PMID- 17343035 TI - [Platelet responsiveness to clopidogrel in patients with coronary syndrome. Comparison of platelet aggregation induced by ADP and flow cytometric analysis of intraplatelet VASP phosphorylation]. AB - Although antiplatelet therapy with ASA-clopidogrel reduces the risk of cardiovascular episodes after PCI, a substantial number of events occur during follow-up. Sustained platelet reactivity under dual antiplatelet therapy was recently associated with increased risk of recurrent atherothrombotic events after PCI. Whereas it appears significant to determine clopidogrel responsiveness, the accurate platelet function assay is still under investigation. OBJECTIVES: (i) to determine the proportion of "low-responders" or "resistants" patients during coronary syndrome (ii) to identify determinants of interindividual variability response to clopidogrel (iii) to compare aggregometry and VASP phosphorylation measured by flow cytometry. Patients were treated by clopidogrel (300 mg loading dose and 75 mg maintenance dose) and ASA (160 mg) (N=27). Additional treatment by GPIIbIIIa antagonists was given to high-risk patients (N=9). Platelet function was monitored by ADP aggregometry (5, 10, 20 microM) and VASP phosphorylation before any treatment by clopidogrel (d0) and at least five days after (d5). The platelet reactivity index (PRI), expressed as percentage, is the difference in VASP fluorescence intensity between resting (+ PGE1) and activated (ADP) platelets. At d5, low responsiveness to clopidogrel was defined by either (i) a PRI > 67.3% corresponding to the mean value -2SD measured in untreated patients (dO) (ii) or an absolute change (delta d0-d5) in aggregation (ADP 10 microM) < to 30%. RESULTS: PRI, platelet aggregometry to ADP was significantly reduced following clopidogrel treatment (P < 0.01). A wide inter-individual variability to clopidogrel was observed at d5 (PRI from 11 to 83%). Whatever the platelet function used, a large proportion of patients were detected as "low-responders" (37% by VASP, 44% by ADP aggregometry). Absolute change in ADP aggregation was correlated to the variation of PRI (R = 0.559; P = 0.02). Contrary to ADP aggregometry, PRI was not influenced by GPIIbIIIa antagonists or prior administration of ASA. However, the conformity of the two methods to evaluate clopidogrel responsiveness was only 66%. No differences in platelet aggregometry could be observed at d5 between "low" and "good-responders" defined by VASP analysis. At d5, a higher PRI value could be detected in male and patients with history of dyslipemia. CONCLUSION: During coronary syndrome, impaired platelet responsiveness to clopidogrel was observed in a large proportion of patients whatever the platelet function assay used. VASP analysis was found insensitive to GPIIbIIIa or aspirin administration. Possible mechanisms linking clopidogrel "resistance" measured by VASP assay and enhanced thrombogenicity remain to be characterized. Indeed, clopidogrel "resistance" defined by VASP analysis was not associated with higher platelet aggregation. PMID- 17343036 TI - [Influence of percutaneous coronary intervention in non ST-elevation acute coronary syndromes on prescription of secondary prevention medications. Data from the S-Temoin Registry]. AB - BACKGROUND: The interaction between the use of percutaneous coronary intervention (PCI) for non-ST-elevation acute coronary syndromes and the use of secondary prevention medications was analysed in the French S-Temoin Registry. METHODS: The population consisted of 2433 patients seen by their cardiologists at an outpatient clinic 2-12 months after non ST-elevation ACS; the survey was carried out from September 2004 to April 2005. RESULTS: Overall, patients undergoing PCI (75% of the population) had higher levels of prescription of recommended secondary prevention medications. Multivariate logistic regression analysis showed that the use and type of coronary intervention (drug eluting versus bare metal stents) was an independent correlate of the use of dual antiplatelet therapy. In addition, time from the acute episode was also a strong correlate of dual antiplatelet therapy. Statins were also more often used in patients with PCI. CONCLUSION: Patients not treated with PCI are less likely to receive appropriate secondary prevention medications after non ST-elevation acute coronary syndromes. Specific efforts should be directed towards these patients, in particular as regards the prescription of dual antiplatelet therapy. PMID- 17343037 TI - [Therapeutic management of heart failure and left ventricular dysfunction following acute myocardial infarction in French intensive care units]. AB - OBJECTIVE: To evaluate the therapeutic management of cardiac failure after myocardial infarction (MI) in French intensive cardiac care units (USIC) in 2005. METHOD: French cross-sectional observational study conducted in USIC of University Hospital Centres (CHU), General Hospital Centres (CHG), and private clinics. Included patients were hospitalized for MI, with a systolic ejection fraction < or =40% and "having" or "having had" signs of acute heart failure during the hospitalization or diabetes. RESULTS: Overall, 59 sites, including 10 CHU (16.9%), 37 CHG (62.7%), and 12 private clinics (20.3%) included 447 patients. The majority of patients were male (64.9%), > or =70 years (62.7%), hypertensive (53.5%) and diabetic (40.8%). They presented a class II (22.3%), class III (29.5%) and class IV (38.9%) cardiac failure severity according to NYHA classification and 20.4% had a creatinine clearance <30 ml/min. The most prescribed treatments were statines (75.4%), IEC (73.6%), diuretics (71.8%) and betablockers (66.7%). The least prescribed were aldosterone antagonist (16.3%) and calcium channel blockers (6.5%). Treatments were prescribed according to age, degree of cardiac failure and renal function of the patient. CONCLUSION: The present observational study shows improved compliance with European and international guidelines, as regards the medications prescribed at hospital discharge after myocardial infarctions complicated with left ventricular dysfunction. Unfortunately, recommended medications remained less often prescribed in the patients with the most severe characteristics. PMID- 17343038 TI - [Infarction in the per-operative period: check-up, results, treatment, surveillance]. AB - Peroperative infarction (POI) is a frequent and serious event, which is associated with an increase in morbidity and mortality; the risk is aggravated to varying degrees by the techniques of anaesthesia and surgery used. The preoperative evaluation of risk, which combines clinical and paraclinical criteria is described in the algorithm of the new AHA/ACC guidelines. In order to avert these ischemic episodes, beta-blockers must be continued or introduced during vascular surgery. In other types of surgery, they must be considered. It is difficult to diagnose MI in a per-operative context. The electrocardiogram print out and troponin kinetics will identify patients in the postoperative phase that should be oriented towards cardiovascular evaluation and therapy. PMID- 17343039 TI - [Intracoronary thrombectomy with the Export Aspiration Catheter before angioplasty in patients with ST-segment elevation myocardial infarction]. AB - OBJECTIVES: We aimed to assess the safety and feasibility of thrombectomy with the Export Aspiration Catheter (EAC) before angioplasty, and its ability to improve angiographic results in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Distal embolization of atherothrombotic material often occurs during angioplasty in STEMI, compromising optimal myocardial reperfusion. METHODS: We performed a thrombus-aspiration with EAC prior to angioplasty in 64 consecutive patients with STEMI. Successful thrombectomy was defined as an improvement of TIMI flow grade > or =1. RESULTS: Successful thrombectomy (increase of TIMI flow > or =1) was achieved in 40 patients (62.5%). Mean TIMI flow grade increased from 0.7 +/- 1 to 1.9 +/- 1.2 (P < 0.0001) after thrombectomy. TIMI flow grade 3 was observed more frequently after EAC compared with guidewire alone (51.5 vs. 9%, P = 0.0062). Direct stenting was performed in most of patients (N=41, 64%). Distal embolization and noreflow/slowflow phenomenon occurred in 8 patients (12.5%). No vessel injury after EAC thrombectomy was reported. After treatment with balloon angioplasty and/or stenting, final TIMI flow grade 3 was achieved in 54 patients (84.5%). By multivariate analysis, ischemic time <6 h was a significant independent predictor of successful thrombectomy (P = 0.0437). CONCLUSIONS: Our series suggests that EAC thrombectomy prior to angioplasty in the setting of STEMI is safe and feasible. It might reduce the culprit coronary lesion's thrombus burden, leading to improved flow restoration and myocardial reperfusion. Further large randomized studies are warranted to confirm these preliminary results and to assess the impact of thrombus-aspiration on infarct size as well as on clinical outcomes. PMID- 17343040 TI - [The results of the artificial heart]. AB - The artificial heart is no more a dream but a reality. Over the last 40 years, many circulatory assist devices have been developed. First were the pneumatic devices, external or implantable, providing uni- or biventricular support; next were the partially implantable electromecanical devices. We went from the first generation of devices with all components (pump, energy power, control system) outside of the body to the second generation of devices with the pump and the motor implanted inside the body. Recently, the third generation of artificial hearts appeared with all components implanted inside the body allowing better mobility and quality of life. Results depend on the indication and on the kind of artificial heart implanted: partial (native heart still in place) or total (native heart removed). Essentially developped as a bridge to transplant, the artificial heart is now allowed as destination therapy. PMID- 17343041 TI - [Legislative and legal security of supervisory activities in the sphere of protection of consumers' rights and human well-being]. AB - Sanitary legislation plays an important role in supervisory activities ensuring the protection of consumers' rights and human well-being. The paper considers the basic laws and standard acts allowing for legal regulation in this sphere of activities. PMID- 17343042 TI - [Preventive toxicology and preventive medicine]. PMID- 17343043 TI - [Drinking water supply in the Russian Federation: problems and ways of their solution]. AB - Russia having a fifth of the worldwide drinking water resources is faced with considerable difficulties in solving the problems associated with the safe and rational attitude towards water resources, in improving the technologies of drinking water purification and conditioning, in introducing new universal forms of supplying the population with high-quality portable water. Particular emphasis has been recently placed on the setting-up of an effective legal and normative base for the sanitary protection of water sources and the upgrading of the quality of drinking water. Regional (republican, territorial) drinking water supply programs have been worked out up to the period 2010 in 47 subjects of the Russian Federation, with the participation of sanitary-and-epidemiological surveillance systems and approved in accordance with the established procedures. The majority of administrative areas have district and town programs to implement high-priority measures for improving the water supple system. Safe drinking water supply is one of the major components of Russia's national security. Under the established conditions, even in case of the favorable financial position, this cannot be achieved by only engineering decisions (construction and modernization of water-supply networks, use of new equipment and breakthrough technologies). Water service as a type of water consumption is based on the general principles of natural resource management. Its safety should be combined with the strategic objective of water resources utilization and conservation in the catchment basins in the country as a whole. PMID- 17343044 TI - [Hygienic assessment of the hazard of ambient air carcinogenic factors]. AB - The paper shows an extremely greater danger of aerogenic doses of carcinogenic substances entering with smoking products than that of an aerogenic load in the industrial centers. The individual and population risks of cancer due to smoking of the Ukraine's common cigarettes and the economic damage caused by the treatment of this number of patients to the country have been calculated. For a full assessment of the carcinogenic risk of tobacco smoke, it is necessary to determine all its carcinogenic constituents, their precursors, and possible transformation groups at high temperatures. PMID- 17343045 TI - [Hygienic assessment of the risk of ambient air pollution to human health in the Ukraine's industrial towns]. AB - The paper presents the results of a hygienic analysis of ambient air pollution in 18 industrial cities of the Ukraine in 1990, 1996, and 2003 and the calculations of noncarcinogenic and carcinogenic hazards of ambient air pollutions to human health. According to the calculated complex indices P, the cities were ranked by the magnitude of ambient air pollution (an environmental disaster area; extreme, severe, moderate, weak, and permissible pollution). The non-carcinogenic and (total indices, indices for critical organs and systems) carcinogenic risks were estimated for the populations of the studied cities in relation to the level of atmospheric pollution on their territories. Proposals are given for further development of studies. PMID- 17343046 TI - [Impact of oxidative stress on the prevalence of hypercholesterolemia under the conditions of an industrial town]. AB - The level of cholesterol and its distribution by the fractions of lipoproteins of different classes were studied in the dwellers of an industrial town. The persons living in the residential areas characterized by a high oxidative stress were observed to have higher blood cholesterol levels and dyslipoproteinemia. PMID- 17343047 TI - [Place of environmental factors among external causes of death in Russia]. PMID- 17343048 TI - [Experimental evaluation of the protective properties of some nonwoven materials for respiratory protection means and prospects of their use]. AB - The protective properties of nonwoven materials (Spandbond, SMS) used to manufacture 3-5-layer medical masks, by using model physical and bacterial test aerosols, were experimentally assessed. It was shown that the more layers of the materials, the less permeable they became for test aerosols. Three-five-layer masks made from SMS at a density of 42 g/m2 were found to have higher protective properties for oil mist and fine aerosol than those made from Spandbond at a density of 25 g/m2. Five-layer SMS materials at a density of 42 g/m2 have the highest values of bacterial aerosol retention. PMID- 17343049 TI - [Priorities of health-promoting and medical rehabilitation in railwaymen]. AB - The paper describes the priorities of health-promoting and medical rehabilitation in railwaymen working under adverse industrial conditions. The authors define the priorities of selection of occupational groups to be primarily referred for sanatorium-and-spa treatment (by taking into account the profile of disease or major industry-associated risk factors), which regulate the medical criteria for selection of contingents (apparently healthy individuals having risk factors, with early morbid signs and significant forms of underlying occupational and industry-dependent diseases). The periodicity of referrals for sanatorium-and-spa treatment and health-promotion depends on the intensity of and exposure to occupational factors, as well as the mean time of development of major forms of abnormalities. PMID- 17343050 TI - [The physiological and hygienic bases of traffic control on high-speed transport]. AB - The study of high-speed transport drivers' work has indicated that the latter is characterized by high nervous and emotional stress, the required long forced posture, high attention and monotonicity, as well as the physiologically power intensive algorithm that places stringent requirements for the body's functional state. A combination of the above factors significantly deteriorates the drivers' ability to maintain the required level of vigilance, working capacity, and readiness for emergent actions, which requires the introduction of new security systems and the development of complex measures to minimize the influence of the above negative factors. PMID- 17343051 TI - [Individuality of professional adaptation in females engaged in industry]. AB - Heavy female manual labor at a coal-cleaning plant was found to be under the influence of a complex of unfavorable factors. Nervous and emotional stress was deteriorated by the presence of conflict situations and dissatisfaction with relationships in the collective body. Three groups of patients differing in the health status and physical fitness were identified depending on the level of emotional stability. The latter determined the individual strategy of adaptation of the female circulatory system, the rate of reserves expenditure, and the level of stress. PMID- 17343052 TI - [Influence of occupational factors on sailors' health]. AB - The assessment of sailors' health has led to the conclusion that their health changes may have a diversity of etiology, magnitude, but they are always directly due to the state of the factors forming the environment. PMID- 17343053 TI - [Impact of electromagnetic fields on a computer user]. AB - An uncontrolled rise in computerization has generated a basically new dangerous source of electromagnetic fields, which, with combined deteriorating influence of personal computer-related overloads, acquires great importance and places stringent requirements. At the same time, the adverse impact of electromagnetic fields of video displays terminals (VDT) and personal computers (P') has not thoroughly been studied and therefore its assessment is quite ambiguous. Due to the fact that there are no valid experimental data on the existing problem, the authors show it necessary to give particular attention to the comprehensive assessment of negative factors, to provide a strict regulation of work on VDT and P', and to inform the population of this problem. PMID- 17343054 TI - [Sanitary-and-epidemiological control of the quality of dairy foods]. AB - At the Federal state health facility of the Perm Region--the Center of Hygiene and Epidemiology, the authors have carried out chemical and bacteriological tests (n = 410) of 70 raw milk samples taken at various points of sale to examine for compliance with the standards stimulated in the normative SanPin documents. The conventional methods were used to study a number of chemical, biochemical, and bacteriological parameters that characterized freshness, density, acidity, the content of toxic elements, mycotoxins, antibiotics, pesticides, radionuclides, the total number of microbes, etc. The quality and nutritive value of the test milk were characterized according to the findings. The main conclusion of the study was that in quite a number of cases, analyses of the private farm milk sold by farmers on the municipal markets and unpretested by the specialists of the territorial Russian consumer supervisory boards revealed that it was not up to the standards for the quality of the product itself and the material of its package. Unexposed to heat treatment, raw milk should not be used since it may occasionally adversely affect human health. PMID- 17343055 TI - [Effects of food supplements on the safety and quality of seafoods]. AB - The safety of foodstuffs from the hydrocoles made with food supplements is considered. The use in the seafoods of sodium benzoate (E 211), a preservative, monosodium glutamate (E 621), an agent enhancing the flavor of the food, does not provide safety of products, the use of which negative influences human health. PMID- 17343056 TI - [Principal sources of dietary intake of macronutrients in the adult rural population in the Chuvash Republic]. AB - The paper presents the results of determination of the basic sources of macronutrients and energy in the nutrition of the rural population of the Chuvash Republic. The importance of foodstuffs, the sources of nutrients, was determined by factor mathematical analysis, by estimating the weight factors. All the products used in the daily ration were studied, which permitted elucidation of the importance of individual Russia-specific products. In the rural population of the Chuvash Republic, nutrition is unbalanced and caused by both economic features and lack of knowledge about balanced diet and its value for human health. Bread, bakery goods, domestic baked products, potatoes, pork, whole milk products form the basis of their diet. The consumption of vegetables and fruits is very little and restricted to the crop grown in private farms. Sugar is used in the quantities that are considerably greater than those given in the WHO recommendations. PMID- 17343057 TI - [Influence of dairy food rotavirus contamination on morbidity]. AB - The indirect hemagglutation test (IHT) indicated that rotaantigen infection of dairy foods (DF) selected at the milk processing shop in the year of high morbidity due to rotavirus infection (RVI) averaged 12.4%. Laboratory monitoring of DF sold in the year of relative low morbidity could establish that the rate of their rotaantigen contamination averaged 4.8%, as evidenced by IHT; polymerase chain reaction was positive in 19.3% of cases. Comparison of annual trends in the detection rate of rotaantigen in DF and RVI morbidity revealed that there was an increase in DF rotavirus contamination in the cold period of a year, following the seasonal activation of an epidemic process. PMID- 17343058 TI - [Manganese provision in trained and untrained schoolchildren and students in different seasons]. AB - Examination of trained (43 skiers) and untrained senior schoolchildren (31 senior schoolchildren), low-order students-skiers (n = 110) and untrained (n = 17) students, high-order students-skiers (n = 39) and students not going in for sports (n = 60) established that in schoolchildren and students of both groups, the content of manganese in the blood plasma and corpuscles in the trained and untrained schoolchildren and students largely depended on the pattern of muscle activity rather than a season. In young skiers and high-order athletes, the level of manganese in both blood fractions was much higher almost at all stages of a follow-up, especially in the periods of increased training and race loads than that in the untrained persons of their age. In all the groups of senior schoolchildren and students, the dietary intake of manganese was season independent and less than the recommended values, in schoolchildren in particular. In almost all, manganese balance was negative in both winter and summer. The exception was untrained group of students in whom manganese balance was positive in winter due the higher dietary content of the trace than that in other groups. PMID- 17343059 TI - [Autonomic functional changes in students during adaptation to mental work loads]. AB - Autonomic functions were studied at intensive mental work. There was nervous and psychiatric overstress, asthenia, and impaired cardiovascular adaptive processes. Higher sympathetic influences on the heart and vessels associated with vagal effects are of essential value under emotional stress. The nature of these changes is aimed at maintaining cardiac output and circulation at the microcirculatory level. PMID- 17343060 TI - [Influence of social, hygienic, and environmental factors on the health status and physical development of schoolchildren in the Republic of Tyva]. PMID- 17343061 TI - [Morbidity among schoolchildren and vocational college students upon completion of education]. AB - The health status of adolescent schoolchildren and vocational college (VC) students aged 15-18 years was monitored for 3 years. It was found that morbidity rates increased from the 9th to 11th forms in the schoolchildren and from the 1st to 3rd courses in the VC students, pathology and functional disorders most intensively developed in VC girls. On completion of school education, there was an increase in the prevalence of mainly functional disorders among the girls and in that of chronic diseases among young men. The course of nervous and mental disorders was found to become worse in most VC students. The specific features of the formation and development of pathological processes were identified in relation to the profile of VC and the influence of professional and occupational factors. The results of the study provide a means of developing differential health-promotion measures for pupils and students with consideration of gender, age, the type of an educational establishment, and the profile of a vocational college. PMID- 17343062 TI - [Health and nutrition in adolescents of the Primorye Territory]. AB - The paper presents the results of a study of health status and some factors of nutrition in 1900 adolescents aged 10-17 years from the Primorye Territory. A comprehensive assessment of the height and development established health group 1 only in 4.2%, which is 6.5% less than the initial data of preventive examinations at educational establishments. The implication of the morphofunctional status was underestimated in assessing the health status. The findings of the pattern of nutrition in children adolescents from the Primorye Territory point to its irregularity, unbalanced characteristics in terms of basic ingredients, accompanied by low health indices. Metabolic trophotropicity was revealed in the adolescents of the Primorye Territory at the present stage. These processes were most marked in 13-year-old girls. In the average, in every 7 children protein metabolism tended to decrease with the maximum manifestation of these disorders at the age of 11-12 years. PMID- 17343063 TI - [Regional features of organization of a sociohygienic monitoring system]. PMID- 17343064 TI - [Birth body weight and its use in the sociohygienic monitoring system]. PMID- 17343065 TI - [Some results of sociohygienic monitoring and directions in its improvement]. PMID- 17343066 TI - [Determination of milk penicillin residues by the impedance technique]. PMID- 17343067 TI - [Determination of human urinary uranium by the atomic emission technique]. PMID- 17343069 TI - Flying to the rescue. PMID- 17343070 TI - The quiet servant. PMID- 17343071 TI - Pretibial lacerations: management and treatment in the emergency department. PMID- 17343072 TI - Priapism: diagnosis and early referral in emergency departments. PMID- 17343073 TI - Hand injuries in children: a reflective case study. PMID- 17343074 TI - Satisfaction guaranteed? PMID- 17343075 TI - Relationship between the degree of portal hypertension and the onset of spontaneous bacterial peritonitis in patients with cirrhosis. AB - BACKGROUND/AIM: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis but its exact pathogenesis has not yet been elucidated and the role of portal hypertension in the development of SBP has been suggested. The aim of this study was to test the hypothesis that an association exists between the degree of portal hypertension and the occurrence of SBP. METHODS: 292 patients with cirrhosis who underwent a measurement of the hepatic venous pressure gradient (HVPG) were retrospectively studied. Following their ascites profile, patients were classified in three groups: patients with ascites who suffered from SBP, patients with sterile ascites, and patients who had no ascites. RESULTS: Among the 137 patients with ascites, 24 patients suffered from SBP (17.5%). The mean HVPG was significantly different: 20.7 +/- 6.2 mm Hg in the SBP group, 17.5 +/- 5.1 mm Hg in the sterile ascites group and 14.7 +/- 5.6 mm Hg in the group without ascites (p < 0.05). Patients with the most severe portal hypertension (HVPG > or =30 mm Hg) had the highest risk to suffer from SBP (50%). Using the multivariate analysis, only the serum albumin level (p = 0.004) and the HVPG (p = 0.02) were independently correlated with the occurrence of ascites infection. CONCLUSIONS: This study suggests that in patients with SBP the degree of portal hypertension is greater than in the non infected patients. Ascites infection is independently associated with a low serum albumin level and a high HVPG. PMID- 17343076 TI - Improvement of routine diagnosis of intestinal parasites with multiple sampling and SAF-fixative in the triple-faeces-test. AB - BACKGROUND AND STUDY AIM: To perform optimal laboratory diagnosis of intestinal parasites is demanding. Because intestinal parasites are intermittently shedded, examination of multiple stools is imperative. For reliable detection of vegetative stages of protozoa, fresh stools should be examined direct after production, or stools should be preserved in a fixative. These aspects in routine practice are often neglected with as a result lower sensitivity of the diagnostic procedure. With application of the Triple-Faeces-Test (TFT) protocol, where both multiple sampling and a SAF-fixative are included, these practical problems could be overcome. The aim of this study was to compare the recovery of intestinal parasites in faecal specimens using TFT protocol versus the conventional diagnostic method (ether-sedimentation of one fresh stool sample). METHODS: During a three years period, results obtained in routine practice with the TFT protocol were compared with results from examination of sediment obtained with the ethyl-acetate-sedimentation technique of one unpreserved faeces specimen. RESULTS: From 2776 patients, 28.1% were positive for one or more intestinal parasites after examination of the TFT test, compared to 10.3% positivity with the conventional method (P < 0.05). Pathogenic species and non pathogenic species were observed respectively 191 and 449 times with TFT and 105 and 152 times with conventional method (P < 0.05). CONCLUSIONS: The application of the Triple-Faeces Test in routine clinical practice significantly increased recovery of intestinal parasitic infections. PMID- 17343077 TI - Imatinib for the treatment of patients with unresectable or metastatic malignant KIT-positive gastrointestinal stromal tumours: an open-label Belgian trial. AB - BACKGROUND: Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. They are defined immunohistologically as KIT positive tumours. The only effective treatment for malignant GIST was surgery until 2000. Imatinib mesylate (STI571, Glivec) has shown substantial anticancer activity in patients with metastatic or unresectable GIST. PATIENTS AND METHODS: 57 patients who were diagnosed with unresectable or metastatic malignant GIST were entered into this study. The patients were given 400 mg Glivec orally once daily. The dose could be increased to 600 mg orally once daily and then to 400 mg twice daily if tumour progression was noticed. Daily treatment was interrupted or dose was decreased only in the case of limiting toxicities. We evaluated the tumour response and the safety of the drug. RESULTS: 85% of GIST patients showed a partial response or stable disease after 8 weeks of treatment with imatinib. The main side effects were nausea, vomiting, anorexia, skin rash, periorbital oedema and diarrhea. CONCLUSION: This study confirms that imatinib is an active agent against malignant GIST with manageable toxicities. PMID- 17343079 TI - Leptomeningeal carcinomatosis associated with oesophageal adenocarcinoma: two case reports and review of the literature. AB - Leptomeningeal carcinomatosis (LC) is a rare complication of solid tumours. We report two cases of leptomeningeal carcinomatosis in patients with oesophageal adenocarcinoma. Diagnosis of LC can be overlooked without a high index of suspicion. Multifocality of symptoms and signs is the hallmark of LC. The combination of cerebrospinal fluid cytology and magnetic resonance imaging has a high diagnostic accuracy. The prognosis remains poor and therefore all therapies are still palliative. PMID- 17343078 TI - Effectiveness of bougie dilation for the management of corrosive esophageal strictures. AB - BACKGROUND AND STUDY AIMS: Caustic ingestion caused by swallowing a detergent can produce a progressive and devastating injury in the esophagus and stomach. One of the most important outcomes of the corrosive oesophagitis is the stricture formation, which is resistant to treatment. The aim of this study was firstly to determine the relation between agent, inflammation and stricture, and secondly investigate the efficiency of dilation in patients having esophageal stricture due to corrosive oesophagitis. PATIENTS AND METHODS: In this study, 58 cases with post caustic oesophagitis, which had been admitted to our clinic or emergency department between January 1999 and December 2004, were assessed retrospectively. Dilation of esophageal stricture of the cases was performed by Savary-Gilliard bougies. RESULTS: The most frequently ingested substance was alkaline (48.2%). Concerning all the patients, the most frequent location of caustic injury was upper esophagus (36.2%), and grade I injury was the most frequently encountered one (34.4%). Thirty patients (51.7%) developing stricture were treated by repeated dilations. The most common location of stricture was middle esophagus (50%), and severe stricture was the most common one among all stricture grades (46.7%). Alkaline ingestions yielded more severe stricture than acids. Eight of the patients with stricture (26.6%, 8/30), who didn't respond to periodic esophageal dilation, underwent esophageal resection or bypass surgery. CONCLUSION: Dilation with Savary-Gilliard bougies is a quite effective method for stricture after corrosive oesophagitis. PMID- 17343080 TI - Transient recurrent ascites. AB - Angiotensin-converting enzyme (ACE) inhibitors are widely used in heart diseases. We describe a case of a young woman treated with fosinopril. She started experiencing abdominal pain, vomiting and diarrhoea with peritoneal signs on physical examination three years after her treatment has been initiated. She presented ascites and signs of ileitis on imaging studies. She even underwent surgery. The diagnosis of ACE inhibitor-induced angiooedema of the small bowel was made after the fourth episode. Fosinopril was stopped and the symptoms never recurred. The case we describe illustrates clinical presentation, radiological findings and difficulty of making an accurate diagnosis in such a patient. PMID- 17343081 TI - Protein-losing enteropathy in Crohn's disease. AB - Protein-losing enteropathy (PLE) is a rare but severe complication of Crohn's disease (CD) and hypoalbuminemia can be one of the presenting symptoms of this illness. The diagnosis of PLE can only be made after exclusion of malnutrition and liver or kidney failure. Significant intestinal leakage can be caused by mucosal injury, increased lymphatic pressure or dilated lymphatics and has been reported in a large number of diseases. The protein-losing can be diagnosed by assessing the excretion of different radiolabeled macromolecules in the faeces or by the clearance of alpha-1-antitrypsine in stools. The primary approach should be the optimization of the nutritional status. Medical treatment of the underlying disease is primordial. In other cases surgical resection of the most affected areas is inevitable. We report a case of a 21-year-old male with a 4 year history of CD, who developed significant hypoproteinemia with pitting oedema, initially in the absence of any other sign of severe disease activity. A "Cr-chloride albumin excretion confirmed our hypothesis of protein-losing enteropathy. Because of sub-obstruction signs some months later, a laparotomy was performed which revealed a severely affected loop with dilatation of the proximal jejunum. Interestingly, multiple large lymph nodes and dilated lymphatics were seen. A partial jejunal resection was performed for stricturing Crohn's disease. Histology showed severe mesenteric granulomatosis, dilated lymph vessels and granulomatous vasculitis. After the resection our patient improved without further albumin infusions and the oedema resolved. PMID- 17343082 TI - Pericarditis in exacerbation of ulcerative colitis. AB - Acute pericarditis occurs very rarely in association with inflammatory bowel disease (IBD). It has been described both as an extraintestinal manifestation of IBD and as an adverse drug reaction in IBD treatment. We present a case of a 26 year-old female patient with a severe exacerbation of ulcerative colitis, who was previously under long-term treatment with mesalazine and low-dose prednisone. The literature on pericardial involvement in IBD is reviewed. PMID- 17343083 TI - New insights into the cellular immunology of the intestine in relation to the pathophysiology of inflammatory bowel diseases. AB - The authors review advances about altered immunological cellular mechanisms in inflammatory bowel diseases (IBD). The innate immune response might play a role in the inductive phase : epithelial barrier defect, production of inflammatory cytokines and defective neutrophil function. Dendritic cells have a pivotal role, since they sense the nature of the micro-organisms in the intestine in order to drive either adaptive immune responses through IL-12 or IL-4 and co-stimulatory molecules, or immunotolerance through regulatory T cells (Tr). T helper(Th)1 cytokines (IFNgamma, TNF-alpha, IL-12) are secreted in excess in Crohn's disease (CD) whereas in ulcerative colitis an atypical Th2 immune response (IL-4, TGFbeta) has been reported. However, activation of Th can only lead to effective immune response if co-stimulatory molecules expressed on activated T cells bind to their specific ligands on the antigen-presenting-cells, mesenchymal and endothe-, lial cells. This binding is necessary to generate an effective immune response, to enhance expression of adhesion molecules and T cell recruitment, promoting chronic inflammation in IBD. A defective function of Tr might contribute to excessive T cell response. Innate CD4 + CD25 + Tr derived from the thymus represent 5-10% of T cells in peripheral lymphoid organs. Acquired peripheral Tr downregulate the immune response through IL-10 and TGF-beta production. In IBD effector T cells might downregulate the development of Tr cells in the thymus. Another defective mechanism in CD is T cell resistance to apoptosis, leading to inappropriate immune homeostasis and accumulation of T cells in the tissues. New therapeutic agents have been proposed for correcting deficiencies of innate immunity or reducing excessive immune responses, with promising results confirmed by randomized controlled trials. PMID- 17343084 TI - Apoptosis as a therapeutic paradigm in inflammatory bowel diseases. AB - Evidence is increasing that a defect in apoptosis is involved in the pathogenesis of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). CD seems to be the cause of an intrinsic defect in the apoptotic pathway of (autoreactive) T cells, resulting in excessive T cell responses. In UC, an increased rate of apoptosis of epithelial cells is observed. In this review we will describe apoptotic mechanisms and their association to IBD. In addition, we will review how specific therapeutic approaches interact at different levels with the apoptotic pathway. PMID- 17343085 TI - The hygiene hypothesis and inflammatory bowel diseases: role of helminths. AB - The incidence of atopic and immune diseases has dramatically increased during the second half of the twentieth century. This has been attributed to improved sanitation and hygiene with reduced exposure to infections. The concept of this hygiene hypothesis is not new, and is currently used to explain the increasing incidence of a wide area of diseases. Parasitic helminths are powerful modulators of their host's immune system. It is suggested that the reduced exposure to helminths, due to better hygiene conditions, may predispose to the development of inflammatory bowel diseases. This article reviews the current epidemiological, experimental and clinical data supporting the role of helminths in the hygiene hypothesis in inflammatory bowel diseases. PMID- 17343086 TI - Intestinal helminths: a clue explaining the low incidence of inflammatory bowel diseases in Subsaharan Africa? Potential benefits and hazards of helminth therapy. AB - In their review, the authors state that the very low incidence and prevalence of IBD in sub-Saharan Africa cannot be explained by genetic factors since in Black populations of the U.S.A. and U.K., the incidence of these diseases is approaching that of the white populations. Beside helminths whose intestinal infestation is frequent in sub-Saharan Africa, other micro-organisms such as atypical mycobacteria, lactobacilli, etc, might have been reduced in Western population. This is a new variant of the Hygiene hypothesis. After Rook et al., these micro-organisms were acting as adjuvants for induction of T regulatory cells which, associated with antigen-presenting cells secrete IL-10 and TGF-beta, inhibiting the maturation of CD4 T cells to Th1 and Th2 effector cells, and consequently reducing the occurrence of Th1-mediated diseases like Crohn's disease and Th2-mediated diseases like ulcerative colitis. The effects of intestinal helminths on host immunity have been studied in Ethiopian Jews emigrated to Israel. Thorough studies before and after deworming have demonstrated that chronic helminth infestation provokes a state of chronic immune activation with anergy, reversible after deworming. Administration of ova of Trichuris suis, an helminth non pathogenic in man, has given encouraging results in the treatment o Crohn's disease and ulcerative colitis with a good safety record but long-term trials are needed since the potentially harmful effects of helminths on immunity. PMID- 17343087 TI - The utility of wireless capsule endoscopy, as compared with barium contrast study, in a case of Peutz-Jeghers syndrome. PMID- 17343088 TI - A rare case of pancreatic pseudocyst masquerading as hydrocele. PMID- 17343089 TI - [As a participant in an exchange program in Japan: foreign land with familiar changes]. PMID- 17343090 TI - [The art of making correct decisions: "We must retrieve intuition from the dust bin" (interview by Dorit Kobusch)]. PMID- 17343091 TI - [General practice in the hospice--report of experiences: allowing life to take its course]. PMID- 17343092 TI - ["Fast track" in visceral surgery--3: Postoperative care": the emphasis is on restoring patient activity]. PMID- 17343093 TI - [Problems from general practice--solutions for general practice: managing chronic wounds]. PMID- 17343094 TI - [Kidney transplantation as therapy option--1: A gain in life expectancy and quality of life]. PMID- 17343095 TI - [Redu-Fix--a model for reducing physical restraint: protecting nursing home residence from mobility limitations]. PMID- 17343096 TI - [Protection of patients or deprivation of freedom: assessing each case individually]. PMID- 17343097 TI - [Recognizing and answering ethical questions in routine nursing care: methodological models support decision making]. PMID- 17343098 TI - [Nursing science in the German speaking countries--a position statement]. AB - Based on the definition of the terms "nursing" and "science" nursing science is defined as "the scientific study of situations in which people care for themselves or others". A nursing theory is developed by means of nursing research. The knowledge derived from nursing science is related to nursing diagnoses, interventions and outcomes. Study courses and research programmes with main focus on nursing science are required for the development of nursing science. In German-speaking areas study programmes of nursing management and nursing education are frequently referred to as programmes of nursing science, although their priorities are significantly different. The main focus of both theory and research is rather put on the reference sciences of nursing science than on the actual contents of nursing science. This is quite similar to nursing research. In Germany and Austria as well in Switzerland study courses of nursing science and doctorate programmes are required that put their main emphasis on nursing knowledge. The current stage of development of nursing science has to be critically reviewed to that effect. PMID- 17343099 TI - [Recognizing and understanding diseases: pulse irregularity as guiding symptom]. PMID- 17343100 TI - [Preventing falls by low beds with variable level lateral security rails: combining patient safety and mobility]. PMID- 17343101 TI - Impact of combination medical therapy on mortality in patients with acute coronary syndromes. AB - INTRODUCTION: Conventional risk stratification after acute myocardial infarction is usually based on the extent of myocardial damage and its clinical consequences. However, nowadays, more aggressive therapeutic strategies are used, both pharmacological and invasive, with the aim of changing the course of the disease. OBJECTIVES: To evaluate whether the number of drugs administered can influence survival of these patients, based on recent clinical trials that demonstrated the benefit of each drug for survival after acute coronary events. METHODS: This was a retrospective analysis of 368 consecutive patients admitted to our ICU during 2002 for acute coronary syndrome. A score from 1 to 4 was attributed to each patient according to the number of secondary prevention drugs administered--antiplatelets, beta blockers, angiotensin-converting enzyme inhibitors and statins--independently of the type of association. We evaluated mortality at 30-day follow-up. RESULTS: Mean age was 65 +/- 13 years, 68% were male, and 43% had ST-segment elevation acute myocardial infarction. Thirty-day mortality for score 1 to 4 was 36.8%, 15.6%, 7.8% and 2.5% respectively (p < 0.001). The use of only one or two drugs resulted in a significant increase in the risk of death at 30 days (OR 4.10, 95% CI 1.69-9.93, p = 0.002), when corrected for other variables. There was a 77% risk reduction associated with the use of three or four vs. one or two drugs. The other independent predictors of death were diabetes, Killip class on admission and renal insufficiency. CONCLUSIONS: The use of a greater number of secondary prevention drugs in patients with acute coronary syndromes was associated with improved survival. A score of 4 was a powerful predictor of mortality at 30-day follow-up. PMID- 17343102 TI - Evidence on combined therapy after acute coronary syndrome. PMID- 17343103 TI - Efficacy claims for new drugs without clinical trial outcome data: problems and pitfalls. AB - The definition of efficacy of a cardiovascular treatment is frequently based on its impact on surrogate endpoints. These can be laboratory results, physical signs or images that are used in clinical trials as a substitute for clinically relevant endpoints, representing how patients feel, function or survive and that supposedly predict treatment efficacy. Similar efficacy claims can be made for different drugs, based on their similar effects on the same endpoints. This approach involves generalization from one therapeutic class to another or, within the same class, from one molecule to another, thus implying that the benefits of a non-evaluated drug will be the same as those of another that has been carefully evaluated. Such generalization is more common when dealing with two drugs from the same class that are similar in chemical composition, but is less reliable when the two drugs belong to different classes. In this article we discuss the legitimacy of efficacy and safety claims for new cardiovascular drugs without outcome data from large clinical trials, based on the similarity of effects found with similar drugs that have clinical trial outcome data. PMID- 17343104 TI - Familial apical hypertrophic cardiomyopathy with aneurysmal evolution--an unusual form. AB - The authors present the case of a 76-year-old patient with multiple vascular risk factors, admitted with acute coronary syndrome. The initial electrocardiogram was compatible with evolving anterior wall myocardial infarction and the echocardiogram showed an image interpreted in this context as left apical pseudoaneurysm. Complementary echocardiographic findings of atypical apical hypertrophy and echocardiographic screening performed on close relatives suggested apical hypertrophic cardiomyopathy as the most likely diagnosis, later confirmed by genetic study. This unusual presentation with evolution to ventricular aneurysm is probably due to progressive left ventricular apical remodeling and an echocardiographic image similar to that described points to the diagnosis of this entity. We emphasize the rarity of this phenotypic expression of apical hypertrophic cardiomyopathy, in particular with familial association. PMID- 17343105 TI - Arterial endothelium and atherothrombogenesis II--the role of endothelial dysfunction in atherothrombotic lesions. AB - When cardiovascular risk factors prevail, the endothelial phenotype evolves to a dysfunctional state that is characterized by decreased endothelial-dependent vasodilation and the expression of proinflammatory, procoagulant, pro-oxidant and proliferation signals. Together, these alterations cause perfusion anomalies, promote the development and progression of atherosclerosis, and lead to atherosclerotic cardiovascular events. There is evidence that endothelial dysfunction is a predictor and prognostic risk factor of cardiovascular events, and characterization of the state of endothelial function in all susceptible individuals is strongly recommended as a preventive measure against atherosclerotic disease and to guide and monitor antiatherogenic treatment and atherosclerotic complications. PMID- 17343106 TI - Should the echocardiogram be considered urgent when searching for the source of emboli? PMID- 17343107 TI - Vein of Galen arteriovenous malformation: a rare cause of heart failure. PMID- 17343108 TI - [With much engagement toward personal freedom]. PMID- 17343109 TI - [What is the impact of universal health insurance on nursing?]. PMID- 17343110 TI - [The family suffers as well]. PMID- 17343111 TI - [A Spitex service for Azuga (interview by Margrit Bachl)]. PMID- 17343112 TI - [When words are not the world]. PMID- 17343113 TI - [Much comes together here and I can take it further (interview by Margrit Bachl)]. PMID- 17343114 TI - [Challenging nursing also advances nurses]. PMID- 17343115 TI - [Health--one of China's great deficiencies]. PMID- 17343116 TI - [Descent into hell: a shameful nerve is responsible]. PMID- 17343117 TI - [Reality and challenges of the XXIth century]. PMID- 17343118 TI - [4 generations united]. PMID- 17343119 TI - [The Liege Medical Journal at the crossroads]. PMID- 17343120 TI - [Image of the month. Aortic valve prosthesis: scanner contribution]. PMID- 17343121 TI - [Image of the month. An intrauterine pregnancy after endometrial ablation]. PMID- 17343122 TI - [Rupture of a giant external iliac aneurysm six years after an aorto-bifemoral bypass]. AB - We report the case of a patient operated on for an aorto-iliac aneurysm with an aorto-bifemoral bypass who presented a metachronous iliac aneurysm rupture, six years later, because of aneurysmal degeneration. We performed bipolar ligation of the external iliac artery and an end-to-end anastomosis of the prosthetic limb to the common femoral artery. We discuss aneurysms of the external iliac artery, characterised by their rarity, their specific morbidity and mortality. PMID- 17343123 TI - [Paroxysmal iatrogenic acne and the epidermal growth factor receptor inhibitors (EGFR)]. AB - Paroxysmal drug-induced acne is a peculiar condition recognized for decades in dermatology. It can be induced by a variety of drugs. In recent years, the epidermal growth factor receptor inhibitors used in oncology have shown this type of adverse effects. The pathogenic mechanism is likely related to the EGF implication in the rupture of the microcomedo wall resulting in the perifollicular inflammatory reaction typical for acne. Other cutaneous adverse effects have been reported with anti-EGFR drugs including paronychia and xerosis. The dermatological treatments of these drug-induced disorders must be adequately targeted. PMID- 17343124 TI - [Screening for colorectal cancer]. AB - Colorectal cancer is the second leading cause of death in Northern countries and need a national screening program to reduce mortality and improve quality of life. Screening has to be cost-effective and acceptable for patients. Many screening tools, invasive or not, are existing and often debated: FOBT, sigmoidoscopy and complete colonoscopy. New tools are in development and have to be evaluated in current practice: virtual colonoscopy, new endoscopic technologies, DNA on faeces or proteomics with markers in serum. PMID- 17343125 TI - [Treatment of recurrent pericarditis: case report and review of literature]. AB - Benign acute pericarditis is a common disorder. Recurrence is probably the most troublesome complication, characterized by a return of pericardial pain after recovery from an episode of typical acute pericarditis. Treatment of recurrence is often difficult and the guidelines issued by scientific societies remain vague. A number of investigators published enthusiastic reports on the efficacy of colchicine as adjuvant treatment of recurrent pericarditis and other authors suggested that colchicine should also be used as part of the treatment regimen of acute pericarditis. Colchicine is effective and safe and may be proposed as treatment of choice, especially in the idiopathic form. Treatment with corticosteroids exacerbates and extends the course of recurrent pericarditis and attenuates the efficacy of colchicine. PMID- 17343126 TI - [The ostium primum or partial atrioventricular septal defect]. AB - Often assimilated to simple inter-atrial communication, the ostium primum, or partial atrio-ventricular septal defect, is an entity that is characterized by a different embryological mechanism and requires some specific surgical expertise. Basically, knowledge of the morphology of the common atrioventricular valve with 5 components, the topography of the A-V node and His bundle, and the ventricular consequences of the absence of atrio-ventricular septal structures must be taken into account. PMID- 17343127 TI - [Clinical use of D-dimer testing]. AB - D-dimers are fibrin degradation products which are released during local or systemic activation of coagulation. D-dimer testing is widely used for the work up of patients suspected of deep vein thrombosis or pulmonary embolism. Interpretation of D-dimer levels must take into account the sensitivity and specificity of the assay. The specificity is usually low, and increased D-dimer levels are encountered in many non-thrombotic situations. The sensitivity varies among the different testing methods and is maximal with ELISA assays. Highly sensitive assays allow exclusion of venous thromboembolism when D-dimer levels are normal, without further imaging. However, this diagnostic strategy may only be used safely when the clinical probability of thromboembolism is low to moderate. When combined with other tests of coagulation, D-dimer testing is also useful in the diagnosis of disseminated intravascular coagulation. PMID- 17343128 TI - [Cerebral autosomal dominant arteriolopathy with subcortical infarcts and leucoencephalopathy]. AB - Cerebral Autosomal Dominant Arteriolopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is a recently but increasingly recognized cause of migraine with aura, early and recurrent strokes, and dementia, with an autosomal pattern of transmission. The disease is a widespread vasculopathy, but it is clinically expressed in the CNS only. Cerebral MRI is always abnormal in symptomatic patients, and sometimes in asymptomatic but affected individuals. It shows more or less confluent hypersignals on T2-weighted and flair images. A spectrum of mutations in the Notch3 gene on chromosome 19 are responsible for the disease. There is no specific treatment and the prognosis is poor. We followed three patients from 2 families with genetically confirmed CADASIL and we present their clinical characteristics. We discuss current data on this rare, but non exceptional arteriolopathy. PMID- 17343129 TI - [How I prevent...herpes zoster by vaccination]. AB - Herpes zoster (HZ) results from reactivation of the varicella-zoster virus (VZV), which remains latent in the dorsal root ganglia after varicella. HZ predominantly affects people over 50 years of age without gender distinction, and its incidence increases with age. The most feared complication of HZ is the zoster-associated pains (ZAP), which encompasses the prodromal, concomitant and post-zoster persistent pains. The latter neuralgias are particularly invalidating and notoriously difficult, or even impossible to abate with current therapies. Until now, the best ZAP prevention was achieved by antiviral treatment given during the earliest phase of the eruption. This treatment certainly reduces the duration and intensity of ZAP, but exerts little influence on post-zoster persistent pains. A vaccination boosting the specific anti-VZV immunity in order to decrease the HZ incidence and post-zoster pains appears promising. A recent study performed on 38.546 immunocompetent patients aged over 60 years assessed the efficacy of a single injection of an anti-zoster vaccine (Zostavax). The incidence of HZ and post-zoster pain was decreased by 50% and 66%, respectively. Vaccination could be considered as a valuable option to alleviate the feared complications of HZ. PMID- 17343130 TI - [ADOPT study: which first-line glucose-lowering oral medication in type 2 diabetes?]. AB - ADOPT ("A Diabetes Outcome Progression Trial") is a double-blind, controlled clinical trial that aims at assessing the efficacy of rosiglitazone, as compared to metformin or glibenclamide, in maintaining long-term glycaemic control in patients with recently diagnosed type 2 diabetes. It randomized 4,360 patients who were followed for a median of 4.0 years. The cumulative incidence of monotherapy failure (defined as a confirmed level of fasting plasma glucose level of more than 180 mg/dl) averaged at 5 years 15% with rosiglitazone, 21% with metformin, and 34% with glibenclamide. This represents a risk reduction for rosiglitazone of 32% as compared to metformin and 63% as compared to glibenclamide (P < 0.001 for both comparisons). Rosiglitazone was associated with more weight gain and edema, metformin with a higher incidence of gastrointestinal events and glibenclamide with a higher risk of hypoglycaemia (P < 0.001). In conclusion, ADOPT showed better glycaemic durability with rosiglitazone monotherapy, compared to metformin or glibenclamide. The potential risks and benefits, the profile of adverse events, and the costs of the three drugs should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes. PMID- 17343131 TI - [Reported adverse reactions of veterinary drugs and vaccines in 2005]. AB - We received 105 reports of suspected adverse events (SARs) following the use of veterinary drugs for the year 2005. This corresponds to a 35% increase compared to 2004. Practicing veterinarians sent most of these declarations. 73% of these concerned drugs used on companion animals. Antiparasitic drugs approved for topical use were the most frequently represented group with 48%, followed by drugs used to treat gastrointestinal disorders (11%) and drugs used off-label (14%; other target species or other indication). For the first time 2 declarations concerning the application of permethrin containing spot-on preparations used by mistake on cats were received. An overview of 20 declarations about adverse reactions following application of different vaccines is also presented with emphasis on the problem of fibrosarcoma in cats. We are pleased by the growing interest shown by practicing veterinarians for the vigilance system and hope to further develop this collaboration in the future. PMID- 17343132 TI - Prevalence of heart disease in symptomatic cats: an overview from 1998 to 2005. AB - A total of 408 cats with various cardiovascular problems has been presented to two investigational clinics during the last 8 years. The number of yearly examinations has steadily increased during this period. Definitive cardiovascular disease was diagnosed in 287 cats, whereby hypertrophic cardiomyopathy (HCM) was the most common diagnosis with 67.6%. Congenital cardiovascular malformations were found in 11.8% of the cases. Ventricular septal defect (VSD) was the most frequent anomaly, in contrast to previously published studies. The ECG was found to be relatively non-specific and insensitive for the diagnosis of heart disease: Its usefulness lies in the recognition and diagnosis of cardiac arrhythmias. The radiographically recognized changes were also non-specific for certain heart diseases. Radiographs of the thorax are especially useful in the evaluation of cardiomegaly, and secondary signs of congestion. PMID- 17343133 TI - Echocardiographic screening of purebred cats: an overview from 2002 to 2005. AB - During the last 3 years, a total of 144 cats underwent echocardiographic screening at two investigational clinics before being admitted for breeding. The number of cats presented for that purpose has constantly increased. 8.3% of cats were diagnosed as having hypertrophic cardiomyopathy and 6.9% were diagnosed as suspicious. Male cats were more affected than females (9.4% vs 7.7%). In 4.2 of all presented cats, a congenital cardiac malformation was recognised, most often tricuspid valve dysplasia. PMID- 17343134 TI - [Measurement of the attention time in the horse]. AB - A study carried out on 49 horses showed that it is possible to measure the attention time by operant conditioning. After teaching horses an instrumental task using a signal, we were then able to test their attention time by asking them to prolong it increasingly while setting success and failure criteria. Two tests were performed 3 weeks apart. The 2nd test was feasible without relearning, a proof of memory, and was repeatable, a proof of consistency in the attention time. A significant difference was observed between the 3 age groups. Young horses often performed very well during the 1st test but their attention dropped in the 2nd test while older horses were more stable with respect to attention and even increased it slightly. The study shows that there are individual differences but it was not possible to prove a significant influence of breed, gender and paternal influence. Consequently, learning appears to be one of the most interesting approaches for evaluating the attention of horses and for observing their behaviour. PMID- 17343135 TI - Effect of intravenous calcium on the serum concentration of inorganic phosphorus after oral administration of sodium phosphate. PMID- 17343136 TI - [Pregnancy and the mechanical prosthetic valve: dilemmas about the choice of antithrombotic prophylaxis]. AB - Two pregnant women aged 32 and 34, both of whom had mechanical prosthetic mitral valves, for which they were using low molecular weight heparin. One developed orthopnoea and dyspnoea at 36 weeks amenorrhoea, and the other suffered an acute myocardial infarction at 18 weeks. Both had valvular thrombosis. Following effective treatment, both women delivered at term and one week later after an uncomplicated course, were discharged home from hospital. Clinicians caring for pregnantwomen with mechanical prosthetic valves are faced with a dilemma when trying to provide optimal treatment. Inadequate anticoagulant therapy can result in thrombosis of the mechanical prosthetic valve while, on the other hand, anticoagulant therapy is associated with foetal and maternal bleeding and teratogenic effects. Pregnant women with mechanical prosthetic valves should be thoroughly counselled before or shortly after the confirmation of pregnancy regarding the risks associated with available anticoagulant options, allowing them to make an informed decision concerning the best management plan. This is an algorithm for optimal care of these patients. PMID- 17343137 TI - [Gait disorders due to neurological conditions]. AB - Gait disorders are seen frequently and often have a neurological cause. The clinical management of patients presenting with a gait disorder is often complicated due to the large number of diseases that can cause a gait disorder and to the difficulties in interpreting a specific gait disorder properly. In addition, the currently available classification systems are confusing. Gait disorders can be classified into the following categories: antalgic, paretic hypotonic, spastic, vestibular, ataxic, hypokinetic-rigid, cautious, or functional. A correct interpretation of the gait disorder is important as this determines the diseases to be considered, the auxilliary investigations that have to be carried out, and the selection of rational therapeutic options. PMID- 17343138 TI - [Methicillin-resistant Staphylococcus aureus (MRSA) in the community]. AB - Methicillin-resistant Staphylococcus aureus (MRSA) infections have been confined to healthcare centres for decades. However, MRSA infections are increasingly seen in young healthy individuals with no exposure to healthcare centres. These community-acquired MRSA (CA-MRSA) strains differ from healthcare-associated MRSA (HA-MRSA) strains in various ways. For example, CA-MRSA is strongly associated with the staphylococcal cassette chromosome mec (SCCmec) type IV and the toxin Panton-Valentine leukocidin. CA-MRSA spreads relatively easily but often remains susceptible to non-3-lactam antibiotics. Given the epidemic potential of CA-MRSA strains, there is a high probability that the number of CA-MRSA infections will increase in The Netherlands. In order to prevent and control CA-MRSA outbreaks in the community successfully, the restrictive Dutch antibiotic policy must be followed with strict infection prevention measures. PMID- 17343139 TI - [Diagnostic image (311). A newborn with a strange leg. Congenital knee luxation type I (genu recurvatum)]. AB - A newborn girl's right leg was fixed in hyperextension due to congenital knee luxation type I (genu recurvatum). PMID- 17343140 TI - [No increase in medical consumption in general practice after induced abortion]. AB - OBJECTIVE: To compare medical consumption in general practice between women who underwent an induced abortion and women who did not. DESIGN: Historical cohort study. METHOD: We selected 19o women who underwent an induced abortion in the period 1975-2004 and 145 control patients. Women were selected from the Continuous Morbidity Registration from the University Medical Centre St Radboud in Nijmegen, The Netherlands. Patient records were reviewed to assess socioeconomic background variables and medical consumption in the 3 years before and 3 years after the abortion. Patients were divided into 3 cohorts, based on time period. RESULTS: Patients who underwent an abortion had no increase in medical consumption in general practice after the abortion, compared with before the abortion. They also had no increase in visits to the general practitioner with psychosocial or psychiatric problems after the procedure, nor were they prescribed more medication. Compared with the control group, however, women who elected to have an induced abortion had increased medical consumption and more psychosocial consultations before and after the procedure. During the study period, medical consumption and the number of psychosocial and psychiatric consultations increased in women who had an induced abortion but decreased in those who did not. CONCLUSION: Women who underwent induced abortion had greater medical consumption and more psychosocial problems than those who did not. However, medical consumption and the prevalence of psychosocial problems were similar before and after the procedure. Therefore, induced abortion did not lead to increased medical consumption. PMID- 17343141 TI - [Late postpartum eclampsia]. AB - A 36-year-old woman, who had given birth once before, had an eclamptic epileptic seizure eight days after caesarean delivery of healthy premature twins. Severe headache and loss of vision, leading to blindness, had not been recognised as prodromal signs by the healthcare professionals involved. Thereafter, she suffered a generalised epileptic seizure with tongue bite. She recovered fully after treatment with magnesium sulphate and nifedipine. Eclampsia is a severe condition with high rates of maternal complications, such as abruptio placentae, disseminated intravascular coagulation, neurological problems, pulmonary oedema, acute renal insufficiency and even death. Recognition of prodromal symptoms like headache, visual disturbances and upper abdominal pain is of the utmost importance. Magnesium sulphate intravenously is the treatment of choice. About 25% of the cases of postpartum eclampsia develop 2-28 days after delivery. A history of pre-eclampsia before or during the delivery is often absent. There is a relative increase in the incidence of late postpartum eclampsia, possibly because of misinterpretation ofprodromal symptoms, as illustrated by this case report. Every physician should be able to recognise the symptoms of pre-eclampsia and be aware of the possible consequences. PMID- 17343142 TI - [Pseudomyxoma peritonei; a rare tumour that can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy]. AB - Three patients, men aged 47 and 30 and a woman aged 48 years, presented with appendicitis-like symptoms, progressive abdominal distension, and an ovarian pelvic mass, respectively. All three were diagnosed with pseudomyxoma peritonei. Treatment consisted of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). After a mean follow-up of 64 months (range: 19-89) after initial treatment, the second patient had died of disease progression but the other two were alive and free of disease. Pseudomyxoma peritonei is a rare disease, characterised by progressive intraperitoneal accumulation of mucinous ascites, produced by a mucinous tumour mass on the peritoneal surfaces. The primary tumour is usually a mucinous adenoma of the appendix. Treatment by cytoreductive surgery and HIPEC can result in a 5-year survival rate of more than 80%, depending on the histopathology and the completeness of the cytoreduction. Recognising pseudomyxoma peritonei in an early stage, when complete cytoreduction is still achievable, may result in a considerable improvement in survival. PMID- 17343143 TI - [Fractures in full-term neonates]. AB - It has recently been suggested in the media that fractures in full-term neonates might be caused by non-accidental injury. It is well known that a traumatic birth can result in fractures in the neonate. To evaluate the incidence of unexplained fractures in full-term neonates, we analysed data from the Netherlands Perinatal Registry, containing admission data on neonates from all 10 Neonatal Intensive Care Units and 60% of the level II hospitals. In 1997-2004, 158,035 full-term neonates were admitted. In 1174 of these (0.74%), fractures were demonstrated. In 227 of these 1174 neonates (19%), no cause for the fracture could be found: obvious trauma during birth or congenital bone disease was excluded. In 12 of the 227 full-term infants with an uneventful birth a fracture of the humerus was found, and in 3 a fracture of the femur. In all other cases there was a fracture of the clavicle. The authors conclude that fractures can occur in full-term neonates even after an uneventful vaginal birth or elective caesarean section. A neonate with pain may have a fracture, also after a normal birth. PMID- 17343144 TI - [Celebration speech marking the 150th anniversary of the Vereniging Nederlands Tijdschrift voor Geneeskunde (Association Dutch Journal of Medicine)]. AB - The Nederlands Tijdschrift voor Geneeskunde (NTvG [Dutch Journal of Medicine]) celebrates its 150th anniversary this year. J. van der Meer and S.van 't Hofare the editors of a jubilee book issued to mark the occasion. Two earlier books, issued for the 50th and 100th anniversary of the journal, focused primarily on the history of the association of editors which publishes the NTvG. Unlike these books, a large portion of the current jubilee book is devoted to the history of medicine in the Netherlands in the last 50 years. Of greater importance is that the authors reflect on the relationship between the NTvG, the medical profession and society at large. This relationship has intensified since the 1960's. The NTvG has accomplished its goal of being a general medical journal, but lacks 'the voice of the patient' and editorial comments on current social issues. With respect to the physician-patient relationship, the Netherlands has succeeded more than other countries in diminishing the gap between these two partners. The way the Dutch have dealt with the issue of euthanasia is a clear example. But as to the role of the physician in society, the loss of position and authority, increasing professionalism and specialisation and reluctance to engage in social and ethical debate for fear of losing impartiality have caused the medical profession to assume a marginal position in society, even with respect to its own needs as a group of professionals. At present, there is a clear need for physician citizenship that engages in a broad spectrum of social responsibilities in a professional context. PMID- 17343145 TI - [The cost per year of life gained: trends and internal contradictions]. PMID- 17343146 TI - [The medical curriculum need not take the religious beliefs and cultural background of the students into consideration]. PMID- 17343147 TI - [Bronchial neoplasm in man and women: two distinct illnesses?]. PMID- 17343148 TI - [Spirometry for the primary care physician? For which patient?]. AB - Spirometry is the simplest pulmonary function test and recently became available to all physicians by means of economic and performing devices. Spirometry however requires a good knowledge of indications, realization and interpretation. Expert recommendations, regularly updated by the American and European respiratory societies, specify the necessary conditions for spirometry to provide useful information for the care of patients. PMID- 17343149 TI - [Dyspnea: is medical history still useful for its evaluation?]. AB - Dyspnea is a common symptom and a major cause of medical consultation. Fast and reliable diagnostic work-up warrants minimization of the risks, sometimes vital, incurred by the patient. Despite a growing number of biomarkers including troponins 1, D-dimers, BNP and more recently Apelin, a lung endocrine parenchymal marker, medical history remains the cornerstone of dyspnea clinical work-up. Since the early 90's, clinical investigators have tried to better understand dyspnea by its language. Verbal expressions used by dyspneic patients have been analyzed and progressively linked to given pathophysiological situations. Becoming more fluent with the language of dyspnea would allow physicians to break down any communication barriers and provide the best care possible to patients with dyspnea. PMID- 17343150 TI - [Chronic cough: practical aspects]. AB - A cough is defined as chronic, if it exceeds 8 weeks in length. Post-nasal drip (PND), bronchial asthma and gastro-esophageal reflux (GERD) must be systematically investigated, as these account for 90 percent of chronic cough cases. In addition to medical history and examination which should exclude either a postinfectious cough or coughing related to ACE inhibitor medication, a new evaluation model suggests chest X ray and spirometry as the initial step. A chronic cough is rarely due to one cause as in at least 25% of cases 2 etiologies are present. An effective treatment of chronic cough often relies on several medication trials until its disappearance. After a multidisciplinary approach to chronic cough using this investigative model, the diagnosis of idiopathic or psychogenic cough should remain exceptional. PMID- 17343151 TI - [Passive smoking and respiratory health]. AB - In Switzerland, environmental tobacco smoke (ETS) is widespread and affects 25% of the never smokers. The risk of having lung carcinoma is increased by 23% for never smokers who report exposure to ETS, and women are particularly at risk. Epidemiological surveys diverge on the risk of chronic obstructive pulmonary disease and asthma in adults, but chronic respiratory symptoms are associated with ETS. In children, however, there is increased incidence of asthma when the mother (+36%) or both parents (+50%) are smokers. All-cause mortality (+ 15%) and disease-specific mortality for lung cancer (+65% to + 79%) are increased among ETS exposed never-smokers. PMID- 17343152 TI - [HIV and tuberculosis: new perspectives for diagnosis and treatment]. AB - In developing countries, tuberculosis is the most frequent infectious complication and cause of death of HIV infection and HIV is associated with tuberculosis in a large proportion of patients. Antiretroviral therapy in generic forms at affordable cost have changed the management of both diseases and induced a need for coordination between National AIDS and TB Programmes, training of health care workers and definition of treatment for co-infected patients. For under-funded teams, mastering complex treatment and side effects and long-term monitoring of patients is a challenge. Some national programmes have addressed this challenge with initial success, as demonstrated by Malawi and Benin, this last country with support from Swiss authorities. PMID- 17343153 TI - [Critical approach to the use of blood tests measuring gamma-interferon when suspecting active tuberculosis: clinical cases]. AB - Assays measuring gamma-interferon (INGA) produced by peripheral lymphocytes exposed to antigens specific of Mycobacterium tuberculosis have a very high specificity, thus avoiding false positive results of the tuberculin skin test (TST) such as the BCG or atypical mycobacteria, and allowing a better targeting of treatments for latent tuberculosis infection (LTBI). Their sensitivity is superior to that of the TST in immuno-compromised and elderly subjects, and probably in immuno-competent individuals. They do not allow however to make the distinction between LTBI and active tuberculosis. Furthermore, their sensitivity, although superior to that of the TST, is not sufficient to exclude active TB specially in immuno-compromised subjects. Their main indication remains the detection of LTBI in screening or contact tracing, or in immuno-compromised subjects. PMID- 17343154 TI - [Cervical sprain and chronic disorders: the neurologist's point of view]. AB - The Whiplash Associated Disorders (WAD) are mostly chronic cervical and cephalic pain syndromes. They are often associated with general disorders and with sensorial difficulties. The neurologist evaluates this trouble according to neurochemical and neurophysiological models, hypothesizing a "central hypersensitivity" after a localised peripheral lesion (such as cervical distortion). Other epistemological points of view are certainly legitimate, for example "biopsychosocial" models. From a therapeutic point of view, it seems worth while to try to prevent the development of WAD. When chronic pain is accompanied by difficult life situation, the solution is not simply medical but also social. Faced with a persistent WAD, the therapeutic attitude should be individualised and multidisciplinary, seeking the autonomy of the patient. PMID- 17343155 TI - [Resolvins: new derivates of fatty acids, polyunsaturated (omega-3) with therapeutic potential in inflammatory intestinal diseases]. PMID- 17343156 TI - [Criteria of assessing desire for assisted suicide]. PMID- 17343157 TI - [More than a hundred Nobel price winners face Libyan obscurantism]. PMID- 17343158 TI - [Bad news of anti-obesity vaccine]. PMID- 17343159 TI - [With winter, return of bird flu]. PMID- 17343160 TI - [Jealousy]. PMID- 17343161 TI - [Carcinoids]. PMID- 17343162 TI - [Gastric acid secretion in the rat following end-to-side porto-caval and mesenteric-caval anastomosis]. AB - Marked gastric acid hypersecretion by comparison with a control group was noted following the collection of samples 2 hr after ligation of the pylorus in rats 20 days after subjection to total portosystemic deviation or deviation of the mesenteric flow only into the vena cava. PMID- 17343163 TI - [Modern views concerning the part played by herpes simplex type 2 virus in the pathogenesis of cancer of the cervix]. AB - Recent views on the relationship between carcinoma of the cervix and the herpes virus are presented. While the question is still very open, it can nervetheless be suggested that the type 2 virus plays a part in the pathogenesis of the tumour. Sexual relationships, pregnancy and hormones are important factors in this connection. PMID- 17343164 TI - [Psychological aspects of sexual behaviour in the female]. AB - Various psychological aspects of female sexual behaviour are examined. Certain views relating to psychosexual development during infancy and adolescence are stated and prematrimonial sex is discussed, including questions concerning spontaneous and provoked orgasm. Questions associated with sexuality in married life are also considered. PMID- 17343165 TI - [ASLO levels in 1174 patients admitted to the Turin University Paediatrics Clinic during the period 1996-1972]. AB - Pathological ASLO levels were observed in 1174 patients out of 48,074 admitted to the Turin University Paediatrics Clinic during a four-year period. An analysis is made of this series and the importance of routine determinations as a diagnostic and phophylactic aid is stressed. PMID- 17343166 TI - [Critical appraisal of Jones's criteria in the diagnosis of rheumatism]. AB - Jones's criteria for rheumatism diagnosis are reviewed in the light of clinical and statistical data. Views expressed in the literature are presented, together with a personal case series. It is submitted that no suggestion of absolute value can be admitted for criteria of this type. Complete evaluation of the clinical and, in the case in point, the laboratory data is essential. PMID- 17343167 TI - [ASLO values as a pointer to rheumatism]. AB - Emphasis is laid on the utility of ASLO determination in the detection of rheumatism and reference is made to the 96.5% incidence of above-normal values in a series culled from the University of Turin's Paediatrics Clinic. Pathological values were most commonly in the 333 to 625 U. range and these are proposed as an early warning sign. PMID- 17343168 TI - [The relationship between immunological defence and the development of tumours]. AB - Several of the main features of the relationship between immunological defence and the development of tumours are briefly examined: immunological tolerance, autoimmunisation and the development of reticulum-cell sarcomas in certain mouse strains, and the existence of relationships between pathological proliferation and immunological status abnormalities. The arguments in favour of the existence of immunological tolerance and the meaning of other phenomena relating to immunological status and tumours are briefly discussed. PMID- 17343169 TI - [Histochemical pictures in hamster Pacinian corpuscles in relation to body growth stages]. AB - Morphological and histochemical examination of Pacinian corpuscles (PC) in two batches of 2-3 day-old and 8-month-old hamsters is reported. The method of Gerebtzoff and Koelle was used for AChE and the Goglia modification of Ruffini's auric impregnation technique. AChE in the neonates was either absent or present in the granular centre or a limited area of some CP's, between the capsule and the axial centre. In the adults, a more intense reaction affecting most CP's, particularly high concentrations displayed by the Goglia technique in the granular centre, capsule and the apparatus of Timofeew. Cholinergic fibres were also demonstrated on the CP exterior. These were connected to the capsule and branched with other fibres to form a nervos network that most likely formed the so-called local integrative circuits. It was found that CP's do not reach morphological and functional maturity for some time after birth. Their development is also related to that of their internal and external sensitive and vegetative nerve structures. PMID- 17343170 TI - [Neurochemical and behavioural alterations in animals due to a neurohomologous phospholipids and vitamin B6 association at CNS level]. AB - The effect of a brain cortex phospholipids (BC-PL) and vit. B6 association on animal behaviour and enzymatic activities specific for CNS is studied. The motility and avoidance tests and cerebral L-amino acid aromatic decarboxylase activity were considered. The study was carried out in comparison with methedrine which effects are well known. On the basis of the results the conclusion is drawn that the effects obtained with BC-PL and vit. B6 association are very different from those obtained with methedrine; this suggests a different mecchanism of action at CNS level. PMID- 17343171 TI - [Some points of views on the development of molecular epidemiology]. PMID- 17343172 TI - [Dietary factors and the risk of neural tube defects: a case-control study in Shanxi province, China]. AB - OBJECTIVE: Dietary factors that could potentially be related to the risk of birth defects are still unknown in Shanxi province, a region with high prevalence of neural tube defects(NTDs) in China. The main aim of this study was to evaluate the association between NTDs and local dietary factors. METHODS: A population based case-control study was conducted during 2003-2005 in four selected counties of Shanxi province with 363 NTDs cases ascertained and 523 control babies without any external birth defects. RESULTS: By multivariate logistic regression analysis, we found the NTDs risk was significantly associated with low consumption of meat and legume, high consumption of pickled vegetables, noncentralized supply of drinking water and drinking tea after adjusting for maternal education level and birth defects history. A significant dose response trend was found between the NTDs risk and the lower frequencies of meat and legume consumption and higher frequency of pickled vegetable consumption, with population attributable risks (PAR) of 69.4%, 22.0% and 18.5%, respectively. Mothers who got their drinking water from river or pond during periconceptional period were more likely to have a NTD-affected pregnancy [OR = 3.42, 95% CI: 1.44 8.09, population attributable risk (PAR) = 4.7%] compared with those who utilized tap or well water. Those who drank tea everyday had an elevated risk of having a NTD-affected pregnancy compared with those who didn't (OR = 4.65, 95% CI: 1.41 15.36, PAR = 2.6%). CONCLUSION: Higher intake of meat and legume protects a woman from having a NTD-affected pregnancy, and consumption of pickled vegetables, drinking water from river or pond and drinking tea everyday increase the risk of having such a pregnancy in the study population. PMID- 17343173 TI - [An epidemiological study on degenerated heart valvular diseases among military elderly population in Beijing]. AB - OBJECTIVE: To investigate the prevalence and possible risk factors of senile degenerated heart valvular disease (SDHVD) among military elderly in Beijing. METHODS: 820 individuals, aged 60 or above,are randomly selected from 8202 individuals, in 21 military retirement centers in Beijing. Each individual answers a questionnaire and receives Doppler echocardiographic examination for an observation of the cardiac structure, function and valve condition. A logistic regression analysis is also made to identify possible risk factors and their powers on the prevalence of SDHVD. RESULTS: The prevalence ratio of SDHVD by means of ultrasonic checks among military elderly in Beijing is 13.4%. Among them, the prevalence ratio of SDHVD for age groups of 60-, 70-, and 80 or above are 7.7%, 16.1%, 25.7% respectively. Data from logistic regression shows the following results that SDHVD risk factors include age, hypertention, hyperlipemia, stroke and cadiovascular family history. CONCLUSION: The prevalence of SDHVD among the military elderly in Beijing rises with the increase of age. SDHVD risk factors include age, hypertention, hyperlipemia, stroke and cadiovascular family history. PMID- 17343174 TI - [Studies on the cut-off value of serum pepsinogen abnormality for screening chronic atrophic gastritis and gastric carcinoma]. AB - OBJECTIVE: To evaluate the fast serum pepsinogen level of the healthy adults among local population in areas with high incidence of gastric cancer and to study the suitable cut-off values of serum pepsinogen abnormality for the screen of chronic atrophic gastritis (CAG) and gastric carcinoma (GC) in China. METHODS: Serum PG I and PG II levels were detected with time resolved fluorescence immunoassay (TRFIA). The fast serum PG I and PG I level as well as PG I/PG II ratio of 606 healthy adult residents among local population in Zanhuang county, Hebei province were detected and the normal distribution ranges determined. The relationship between different cut-off values of serum PG I level, PG I/PG II ratio and corresponding pathological changes in gastric mucosae were comparatively analyzed with serum PG detection, endoscopic biopsy and pathological observation in 720 cases of local residents receiving endoscopic examination in the high incidence area of gastric cancer. The efficacy, sensitivity and specificity of different PG I, PG II abnormality cut-off values in the screen p rogram of CAG and GC were statistically analyzed. RESULTS: The serum PG I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. The median level of PG I, PG II and PG I/PG II were 161 microg/L, 14.8 microg/L and 10.5 respectively. Data from comparative studies on serum PG level and pathological changes of gastric mucosae showed that within the serum PG I range from 40 microg/L to 80 microg/L and PG I/PG II ratio range from 3 to 8, sensitivity of the screening program for CAG and GC increased while the specificity decreased along with the increase of cutoff values of serum PG I and PG I/PG II ratio. Results from statistical receiver operator characteristic curve (ROC) analysis suggested that the best cut-off value of PG I and PG I/PG II abnormality for the screening of CAG and GC being PG I < or =60 microg/L,PG I/PG II < or =6 respectively. CONCLUSION: The serum PC I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. Serum PG I < or =60 microg/L and PG I/PG II ratio < or =6 as abnormal cut-off value for the screen of CAG and GC could result relatively good sensitivity and specificity. PMID- 17343175 TI - [Sero-epidemiologic study on the relationship between Chlamydia pneumonia infection and hypertension in Chinese Mongolian population]. AB - OBJECTIVE: To explore the relationship between Chlamydia pneumonia (CP) infection and hypertension as well as the interaction of traditional risk factors and CP infections on hypertension in Chinese Mongolian population. METHODS: 1430 inhabitants living in Tongliao city, Inner Mongolia were selected as research subjects, including 488 hypertensives and 942 normotensives. Enzyme-linked immunoassay technique was used to test CP IgG antibody in the blood serum and SPSS 13.0 Microsoft was used to analyze the data. RESULTS: The prevalence rates of hypertension were significantly different between CP IgG positive and negative groups, However, the trend was attenuated after adjusting age, sex, drinking, smoking, body mass index (BMI) and dyslipidemia. The CP infection rate was significant different in diastolic blood pressure groups, which was significantly higher in 80-84 mm Hg than that in the lowest DBP group. The interaction of chronic CP infection and other traditional risk factors were associated with hypertension in Chinese Mongolian ethnic groups. The ranking with significant sequence from high to low were BMI, dyslipidemia, alcohol intake, sex and age. CONCLUSION: CP infection was not related to hypertension in Chinese Mongolian ethnic groups but the interaction with other traditional risk factors would increase the risk of developing hypertension. PMID- 17343176 TI - [A study on the health status and related influencing factors among 3-year-old children in rural area of Anhui province]. AB - OBJECTIVE: To explore the health status and related influencing factors for 3 year-old children in rural area of Anhui province. METHODS: Clustered random sampling method was used to investigate the general situation of the children and their families as well as to measure height, weight and some other indexes of the children. Health status and its influencing factors were then evaluated. RESULTS: A total number of 418 children were investigated and incidence rates of growth retardation, underweight, overweight, emaciation and obesity appeared to be 4.3%, 1.9%, 0.7%, 0.5% and 14.9% respectively. Z value of development index was high among children with the following situations: heavy birth weight, father was tall, being boys, and having habits as washing hands before meals. However, Z value was low among kids with following characteristics: being the youngest among all the siblings, family income was high, mothers were illiterate as well as taking tocolytic agent and exposure to X-rays during pregnancy, delivered at home, major care taker was mother, mixed feeding in the early 4-month-old, age of supplementary food was less than 3 months, being picky on foods and taking snacks frequently etc. CONCLUSION: Health status of the 3-year-old children in rural area of Anhui province was fine in general, however, more attentionn needs to be paid to pregnant women and child health care takers in the rural areas. PMID- 17343177 TI - [A case-control study on risk factors of drowning among children aged between 1 and 14 in rural areas of Guangxi]. AB - OBJECTIVE: To find out the risk factors of drowning among children aged 1 and 14 in rural areas and to provide evidence for prevention and to reduce such incidents. METHODS: 20 towns being selected as a cluster sampling study and screened out 133 drowning children aged 1-14 from Jan. 1, 2002 to Dec. 31, 2004 were screened. 1:2 matched case-control method was conducted. Data was analyzed with conditional univariate and multivariate logistic regression analysis. RESULTS: Results showed that falling into water took the leading type of drowning among children from the rural areas. The component of drowning displayed that boys was higher than girls. The majority occurred. during the warmer months, in summer and autumn. The places where drowning occurred was mainly at incidence site. Results from single and multiple factors analysis identified four major risk factors as: alcoholic drinking of his/her mother, lack of emergency treatment in the village, the child care-taker did not know what to do when drowning was occurring, the child usually played beside the water site. Factors preventing from drowning were: swimming training, the child caretaker keeping an eye on the child when he/she was swimming, the health condition of the caretaker and the communication with the parents. CONCLUSION: The risk factors of drowning among children aged 1-14 in rural areas were caused by multiple factors. Prevention and control program on drowning should be focusing on supervision, safety water, safety education and teaching swimming. PMID- 17343178 TI - [A cost-effectiveness study on a case-finding program of tuberculosis through screening those suspects with chronic cough symptoms in the rich rural areas]. AB - OBJECTIVE: To study the feasibility and cost-effectiveness of a case-finding program on tuberculosis (TB) in richer rural areas. METHODS: Screening was implemented every three months for a total period of 9 months, in rural areas with high case notification rates. Three villages, each with ten thousand population, were selected to carry out a household screening program. A suspect was defined as who coughed for more than 3 weeks. The suspect was then referred to further diagnosis in county TB dispensary to undergo chest X-ray and sputum test. RESULTS: Of the 86,168 community population screened, 26 TB patients were identified with 7 of them were smear positive. The ratio of effectiveness vs. cost decreased on the second but slightly increased on the third screening program. The direct costs for the 3 screening programs were 6,312,397 and 1637 RMB respectively. Of total direct cost, 5.9% was paid by TB patients, whereas 35.9% was through financing of the county itself. CONCLUSION: The community household screening program could achieve higher case detection rate than passive case-finding approach which could be used in richer areas with low case detection rate in China. PMID- 17343179 TI - [Study on socio-behavioral risk factors of acquired drug resistance of tuberculosis in Sichuan province]. AB - OBJECTIVE: To explore the socio-behavioral risk factors on acquired drug resistance of tuberculosis (ADR-TB). METHODS: Using pair matched case control study, 316 ADR-TB samples from 949 cases and 316 controls (pair matched for age and sex) were selected by systematical sampling method and studied through questionnaires. All the study subjects were selected from outpatients of the institute of TB control and prevention,between June 2002 and June 2005 in Sichuan province. Socio-behavioral risk factors were analyzed with conditional logistic regression and estimated with adjusted odds ratios (OR) and confidence interval (CI). RESULTS: Data showed that the major socio-behavioral risk factors were associated with low economic status, incomplete DOTS, poor compliance and interruption during treatment with adjusted OR and CI as 5.623 (3.462-9.386), 8.875 (6.136-15.442), 6.467(3.942-10.622) and 4.906 (2.477-10.654) respectively. CONCLUSION: ADR-TB could be controlled by taking effective measures against the socio-behavior risk factors. PMID- 17343180 TI - [Study on the genetic diversity among populations of schistosome intermediate hosts within Oncomelania hupensis (Gastropoda: Rissooidea) in Mainland China]. AB - OBJECTIVE: To explore the genetic diversity among populations of Oncomelania hupensis. METHODS: Amplified fragment length polymorphism method was used to amplify the genomic DNA pools of twenty five snail populations from ten provinces, and the genetic diversities among these snail populations were analyzed. RESULTS: The coefficient rates of similarity (GS(DICE)) among twenty five snail populations were ranged was from 0.694 to 0.831 while Nei's unbiased genetic identity was from 0.635 to 0.799. Genetic distance D from 0.169 to 0.306, and Nei's unbiased genetic distance from 0.225 to 0.452. Genetic variation among smooth-shell snail populations was higher than that of ribbed shell snail populations. Twenty five snail populations were divided into three groups: group A including smooth-shell snail from Fuqing of Fujian province and Yizhou of Guangxi province while group B consisted of smooth-shell snail from Dali of Yunnan province and Xichang, Puge, Danleng, Pujiang, Guanghan of Sichuan. Group C was composed of other seventeen snail populations from the Yangtze River drainage below the Three Gorges. CONCLUSION: Big genetic variation was found among these populations of Oncomelania hupensis. The clustering result of snail populations in genomic level was consistent basically with geographical distribution. PMID- 17343181 TI - [Molecular typing of Salmonella paratyphi A isolates from four provinces with pulse-field gel electrophoresis]. AB - OBJECTIVE: To analyze the molecular types of Salmonella paratyphi A strains isolated in the recent years, and to construct the standard S. paratyphi A databank in the laboratory surveillance network PulseNet China. METHODS: S. paratyphi A isolates from 4 provinces were analyzed with the standard pulsed field gel electrophoresis (PFGE) protocol used in PulseNet and their patterns compared. The databank was constructed with BioNumerics. RESULTS: Eleven PFGE patterns were obtained, in which 3 predominant patterns were identifies with a similarity coefficient of 96.3%. The strains of these patterns, accounted for 86.5% of the analyzed strains, appeared in different provinces and years. CONCLUSION: The databank of S. paratyphi A was constructed and could be used in laboratory surveillance of S. paratyphi A in PulseNet China. From the analyses on molecular typing of the isolates, data suggested that the predominant strains might cause the epidemics in different regions. PMID- 17343182 TI - [Development of a model for the diagnosis and risk classification on anthrax through artificial neural network]. AB - OBJECTIVE: Based on data through clinical and epidemiological studies, a model regarding the diagnosis and risk classification on anthrax was developed by artificial neural network (ANN). The model could integrally diagnose anthrax cases, judge the risk tendency in time, and increase the ability of recognizing the anthrax accidents. METHODS: Clinical, laboratory and epidemiological data from anthrax cases was collected and analyzed. The important factors which could greatly influence the results on diagnosis and judgment was chosen and used as the neural units. Through the use of artificial neural network analytic method (back propagation, BP), an intelligent model on the diagnosis and risk classification was developed. RESULTS: Results from the multivariate analysis revealed that: 11 factors including incubation period, chest radiographic and microscopic findings, characteristics on professions etc. were associated with the judgment on the diagnosis and intensity of the epidemics. Through 500 times training on the neural network, the performance error decreased from 6.669 59 to 5.051 19 x 10(-11). The model was then validated. With 100% average correct rate, the predictive value was good. CONCLUSION: It was feasible to use the disease information to develop a diagnosis and risk classification model on anthrax by artificial neural network. With 100% average correct rate, the established model was valuable in practice. PMID- 17343183 TI - [Molecular analysis on the S gene of three Crimean-Congo hemorrhagic fever virus strains in China]. AB - OBJECTIVE: To compare the molecular characteristics of 3 Crimean-Congo hemorrhagic fever viruses(CCHFV) isolated in Xinjiang province. METHODS: YL05035, YT05099 and LT05146 were isolated in 2005 from Hyalomma ticks and viral RNA was extracted from suckling mouse brains infected with these three strains respectively. The polymerase chain reaction(PCR) products of S segments from the 3 strains of CCHFV were directly sequenced. RESULTS: The full-length'S RNA from the 3 strains of CCHFV all comprised 1673 nucleotides with ORF of them including 1449 nucleotides and encoding a protein which comprised 482 amino acids in a viral complementary sense. The sequences indicated that the three strains of CCHFV isolated from ticks in Xinjiang province were highly homologenic. Data from the phylogenetic analysis showed that the obtained sequences were identical. The homology between 3 strains of CCHFV was 99.5%. Their homologies compared with that of the other strains isolated from other region of Xinjiang were also high at nucleotide levels (92.7%-99.8%). The three strains which were clustered together with 7001 strain and 79121 strain (isolated from patient and rat in Xinjiang respectively) was only different by 2%-3%. The genetic difference from the prototype CCHFV Nigerian strain IBAR10200 was 13%. In comparison, the Nigerian CCHFV tick isolate was more divergent when compared with the reference China strains 66019 and with the three variants mentioned above. CONCLUSION: The CCHFV isolated from China comprised a group of genetically high conserved strains. PMID- 17343184 TI - [Study on genetic approach in the detection of Cryptosporidium parvum and Giardia lamblia in acquired immunodeficiency syndrome patients]. AB - OBJECTIVE: To establish genetic method in detecting Cryptosporidium parvum and Giardia lamblia which often coinfected with AIDS patients. METHODS: Cryptosporidium oocysts and Giardia cysts were isolated and purified from fecal samples of the individuals infected with C. parvum and G. lamblia, respectively. Genomic DNAs were extracted. Two pairs of specific primers were designed or synthesized according to the 18S rRNA gene from C. parvum or the triose phosphate isomerase (tim ) gene from G. lamblia. Polymerase chain reaction(PCR) technique was used to amplify the DNA samples from the oocysts and the cysts, and those from the 6 control samples, including Schitosoma japonicum, Toxoplasma gondii , Entamoeba histolytica, Trichinella spiralis, Trichomonas vaginalis and human blood cells. DNA samples from 30 fecal samples of AIDS patients were detected with the same method. RESULTS: One fragment of 500 bp was amplified with the primer of C. parvum, and the other one of 683 bp was amplified with the primer of G. lamblia. Twenty pg and 0.4 pg DNA of C. parvum and G. lamblia could be detected separately. The specificity of these two pairs of PCR primers was confirmed by the failure in the amplification of the control DNA samples. Out of 30 cases of AIDS patients, 7 showed C. parvum positive, while non Giardia was detected. CONCLUSION: Genetic detection method for C. parvum and G. lamblia detection was established which was more sensitive and specific. PMID- 17343185 TI - [Establishment of TaqMan PCR detection method for rabies virus]. AB - OBJECTIVE: To establish a molecular diagnostic method for rabies virus(RV) based on TaqMan PCR. METHODS: BaseD on the rabies virus nucleoprotein gene sequences published in GenBank, RV specific primers and probe were designed by Primer Premier 5.0. The primers and probe were optimized and the sensitivity, specificity,and reproducibility of the system were tested. Quantitative standard curve of RV TaqMan PCR was established. Some RV samples were detected using this system. RESULTS: The optimized primers and probe were 0.6 micromol/L and 0.2 micromol/L. Reproducibility test showed that coefficient variables were all less than 5% in 4 different system. Quantification standard curve based on the genomic copy was drawn. RV detection using the established method proved that TaqMan PCR was more sensitive and easier performed than traditional RT-PCR. CONCLUSION: TaqMan PCR for RV detection had been established, which was more sensitive and specific than the general RT-PCR. PMID- 17343186 TI - [Study on Helicobacter infection in liver tissue from hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the relationship between Helicobacter species and hepatocellular carcinoma(HCC). METHODS: Liver samples resected during operation from 34 patients with HCC diagnosed by histopathology and 20 without primary liver carcinoma as controls were studied. The two groups of sample were cranked out pathologic slice for in situ hybridization of Helicobacter, Helicobacter pylori and Helicobacter hepaticus. Qualitative and quantitative studies were used to assess the correlation of liver tissue Helicobacter infection with HCC. RESULTS: 64.71% (22/34). of the samples of HCC showed positive for Helicobacter specific 16S rRNA-mRNA gene by in situ hybridization, while none was positive in controls (P < 0.01). CONCLUSION: Helicobacter pylori were found in the liver of patients with HCC. PMID- 17343187 TI - [Investigation on levels of serum lipids among 602 patients who had undergone coronary angiography in Zheijian province]. AB - OBJECTIVE: To observe the difference of serum lipid levels between patients with coronary heart disease(CHD) and those without,in Zhejiang province. METHODS: According to coronary angiogram, 602 patients were divided into two groups as group 1 (vessel stenosis > or =50% luminal diameter narrowing of at least one major coronary artery), group 2 (no vessel stenosis or vessel stenosis <50% luminal diameter narrowing ). Their serum triglyceride (TG), total cholesterol (TC), lower density lipoprotein cholesterol (LDL-C), higher density lipoprotein cholesterol (HDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) were measured and analysed. RESULTS: Serum lipid levels of the two groups were all close to the proper scopes of Principles for the prevention of dyslipidemia recommended by dyslipemia group of the editorial board of Chinese Journal of Cardiology. Data also showed that levels of serum TC, LDL-C and non-HDL-C in group 1 were alightly higher than those in group 2 (4.70 mmol/L +/- 1.22 mmol/L vs. 4.49 mmol/L +/- 0.96 mmol/L, 2.63 mmol/L +/- 1.00 mmol/L vs. 2.44 mmol/L+/- 0.77 mmol/L, 3.45 mmol/L+/- 1.14 mmol/L vs. 3.22 mmol/L+/- 0.92 mmol/L, P < 0.05, P< 0.01, respectively). CONCLUSION: Hyperlipidemia was not a inherent characteristic for CHD patients in Zhejiang province. PMID- 17343188 TI - [An intervention study on preventing maternal-fetal transmission of syphilis during pregnancy]. AB - OBJECTIVE: To study the prevalence and principal rules of women with syphilis during pregnancy and to develop relative methods to prevent maternal-fetal transmission. METHODS: A nested case control study on epidemiologic research was used based on review and preview methods on prevention and cure. Targeting pregnant women with syphilis diagnosed during premarital or pregnancy stages and were identified through rapid plasma reagin test (RPR) but confirmed by treponema pallidum test (TP),a total number of 339 women receiving treatment, intervention and being followed throughout the pregnant and neonatal periods. RESULTS: The prevalence of syphilis in pregnancy was 2.33%, and the positive rate in neonatal cord blood was closely associated with the opportunity of getting maternal treatment. The lowest RPR positive rate was among these women who got pregnant after receiving the treatment. The RPR positive rate of neonatal cord blood was positively relative to the mother's RPR titer. The higher was the mother's blood RPR titer, the worse the prenatal prognosis would turn to. CONCLUSION: Mother's blood RPR titer and the opportunity of getting treatment were strongly associated with the positive rate in neonatal cord blood. Pregnancy after receiving the treatment was a powerful measure to prevent the maternal-fetal transmission of syphilis. PMID- 17343189 TI - [Progress on the study of biological characteristic of Rabies virus]. PMID- 17343190 TI - [A survey on HIV/AIDS related discrimination and its influencing factors in a rural community with former commercial blood donors, Shanxi province]. PMID- 17343191 TI - [Investigation on a non-toxigenic cholera outbreak ]. PMID- 17343192 TI - [Surveillance on hemorrhagic fever renal syndrome from 1995 to 2004 in Jinan]. PMID- 17343193 TI - [The clinical features of B cell lymphoblastic lymphoma and outcomes after BFM-90 regimen therapy]. AB - OBJECTIVE: To analyse the clinical features of patients with B cell lymphoblastic lymphoma(BCLL) and the outcomes after modified BFM-90 protocol therapy. METHODS: The clinical features of 14 patients with BCLL were analysed, and compared with that of T cell lymphoblastic lymphoma in the same period. The efficacy and toxicity of modified BFM-90 protocol were analysed. RESULTS: The 14 patients were aged 3 to 18 and diagnosed as BCLL by morphology and immunohistology. One case was in stage I , 2 stage III and 11 stage IV. Most common involved sites were lymph nodes (70% ), skin (50% ) and bone marrow (64% ). One patient received CHOP + HD-MTX, and 13 received modified BFM-90 protocol chemotherapy. Twelve patients (92.3%) achieved complete remission( CR) , 1 patient(7. 7% ) partial remission( PR). The median follow-up duration was 19. 5 months (2 to 44 months). At present 13 patients are alive except one PR patient who gave up treatment and died of disease. The major toxicity of the protocol was myelosuppression, but could be tolerated. CONCLUSIONS: The most common involvement sites of BCLL were lymph nodes, skin and bone marrow. The effectiveness is improved as treated with modified BFM-90 protocol. PMID- 17343194 TI - [Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma]. AB - OBJECTIVE: To investigate the efficacy and toxicity of bortezomib in combination with dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma(MM). METHODS: Sixteen patients(9 males, 7 females, mean age 57. 5 yrs) with refractory or relapsed MM were treated with bortezomib (1. 3 mg/m(2) ) by intravenous bolus twice a week for 2 weeks, or 3. 5 mg once a week in a 21 day cycle, followed by an intravenous injection of dexamethasone 30 - 40 mg. The patients had received one to four courses at least. Response to bortezomib was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation (EBMT) before initiation of each bortezomib chemotherapy course. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3. 0. RESULTS: The median follow-up duration from the beginning of bortezomib treatment was 6 months. Clinical response was observed in 14 patients (87.5%), including near complete response in 6, partial response in 5, minimal response in 3 and no response in 2. The most common adverse events were gastrointestinal symptoms (nausea and vomiting in 12, constipation in 3, severe diarrhea in 3 patients), thrombocytopenia (8 patients) and fatigue(3 patients). The adverse events were subsided on routine supportive care. CONCLUSIONS: Bortezomib in combination with dexamethasone is an effective therapy with a high response rate and manageable toxicities for patients with relapsed or refractory myeloma. PMID- 17343195 TI - [Cytogenetic study on 155 cases of non-Hodgkin' s lymphoma]. AB - OBJECTIVE: To investigate the relationship between histopathological subtype of non-Hodgkin' s lymphoma(NHL) and chromosomal abnormalities, and compare the difference of chromosomal abnormalities between China and the West. METHODS: Routine G banding chromosome analysis and fluorescent in situ hybridization( FISH) were performed on lymph node specimens from 155 NHL patients. RESULTS: Diffuse large B-cell lymphoma( DLBCL) constituted 38.1% of the cases followed by follicular lymphoma(FL) 17.4% , small lymphocytic lymphoma( SLL) 10.3% , peripheral T-cell lymphoma ( PTCL) ( unspecified) 8.4%, and angioimmunoblastic lymphoma 7.1%. One hundred nineteen patients (76. 8%) had clonal chromosomal abnormalities. The incidence of chromosomal abnormalities among FL, SLL, DLBCL, anaplastic large cell lymphoma (ALCL) and precursor T-cell lymphoblastic lymphoma (TLBL) was 96.3% , 87.5% , 86.4%, 83.3% and 83.3%, respectively. Complex karyotype was 86. 3% in DLBCL. The most frequent structural abnormalities in DLBCL involved chromosomes 3, 6, 14 and 1, with had high frequencies of 3q27 (41.2%) and 6q21, 6q23, 6q25 involvement (23.5%). But only 2 cases of DLBCL had classical t( 14; 18) (q32;q21) which was lower than that in the West (20%). The positive rate of IgH rearrangement was 40. 1% in DLBCL by FISH. No 13q14 deletion was found in 16 cases of SLL. Normal karyotype was observed in 8/11 cases with angioimmunoblastic T-cell lymphoma patients. CONCLUSIONS: The distribution of the histopathological subtypes of NHL is different among different geographical areas. The chromosomal abnormalities in DLBCL was comparable between China and the West, but t( 14; 18) was infrequent in the former. The chromosomal abnormalities in SLL was different from the West. The incidence of chromosomal abnormalities in angioimmunoblastic T-cell lymphoma was lower than that in the West. PMID- 17343197 TI - [The effect of cyclin D2 shRNA on the proliferation and apoptosis of LP-1 cell]. AB - OBJECTIVE: To construct cyclin D2 (CCND2) short hairpin RNA ( shRNA) plasmid for repressing the expression of CCND2 in human myeloma cell line LP-1,and to detect its effect on the proliferation and apoptosis of LP-1 cell. METHODS: A CCND2 shRNA model was constructed and cloned into plasmid pGensil-2, then the plasmid was transfected into LP-1 cell in vitro. The CCND2 expression cell proliferation, cell cycle and cell apoptosis of the transfected LP-1 cells were studied by RT PCR, trypanosome staining, flow cytometry and annexin V assay. RESULTS: The transfection efficiency of LP-1 cell was 34. 2%. In the transfected LP-1 cell CCND2 mRNA expression was reduced significantly, the cell growth was inhibited significantly and the cell cycle was partly arrested in G, phase. The apoptosis rate of the transfected LP-1 cell after 72 h was (25.7+/-4.8)%. CONCLUSION: The inhibition of CCND2 in LP-1 cells could inhibit the cell growth and induce cell apoptosis. CCND2 maybe a new therapeutic target. PMID- 17343196 TI - [Expression of CYR61 and VEGF in extranodal nasal-type NK/T cell lymphoma and their significances]. AB - OBJECTIVE: To investigate the expression of CYR61 and VEGF in extranodal nasal type NK/T cell lymphoma and its significance. METHODS: CYR61 mRNA and VEGF mRNA were detected by real-time fluorescence quantitative PCR method in 20 cases of extranodal nasal-type NK/T cell lymphoma. Expressions of CYR61 and VEGF were studied by immunohistochemistry in 40 cases of the tumor. RESULTS: (1) Over expression of CYR61 mRNA and VEGF mRNA was found in 19/20(95.0% ) and 15/20(75.0% ) cases, respectively. (2)Tumor cells expressing CYR61 protein and VEGF protein were detected in 38(95.0% ) and 25 (62. 5% ) of the 40 cases respectively, being no significant difference from the control. Co-expression of CYR61 and VEGF at both the mRNA and protein levels was 95.0% and 65.0% , respectively. Over expression of CYR61 and VEGF at both mRNA and protein levels was found in 8 of the 40 cases. (3) The prognosis of the patients over-expressing CYR61 and VEGF was worse. CONCLUSION: In extranodal nasal-type NK/T cell lymphoma, the expression level of CYR61 and VEGF was changed and it may be of prognostic implication of PMID- 17343198 TI - [SHP-1 gene's methylation status of Daudi lymphoma cell and the demethylation effect of 5-aza-2'-deoxycytidine]. AB - OBJECTIVE: To explore the transcription regulation of 5-aza-2'-deoxycytidine(5 Aza-CdR) on SHP-1 gene and its effects on Daudi cell line growth. METHODS: MTT method and flow cytometry were used to detect the growth and apoptosis of Daudi cells after treated with different dosage of 5-Aza-CdIR. Bisulfite sequencing PCR ( BSP) , T-A cloning and sequence analysis were evaluated for methylation status. The SHP-I mRNA and protein were determined by reverse transcription polymerase chain reaction (RT-PCR) ,immunohistochemistry. RESULTS: (1)After 7 d treatment with 2. 00 micromol/L of 5-Aza-CdR, all cytosines (C) in Daudi cells genome DNA were converted to thymidine, and SHP-1 mRNA and protein expressed again in the cells while those Cs in CpG dinucleotides in untreated Daudi cells remained Cs; (2)5-Aza-CdR inhibited the cell growth,The effects within certain extent were dose and time dependent:after 72 h treatment with 5-Aza-CdR at 200. 00, 20. 00, 2. 00 and 0. 20 micromol/L, the inhibitive rates were 72. 0% , 65. 1%, 51. 5%, 28.8% ,23.4% respectively; (3) 5-Aza-CdR increased apoptosis rate of tumor cells with a dose and times dependent manner within certain extent, too:at the 1,3,5 d treatment with 5-Aza-CdR 2. 00 micromol/L,the apoptosis rates were 2. 3% ,10. 8 % and 17. 1% ; respectively. (4) 5-Aza-CdR also changed cell cycle of tumor cells: at 24 h treatment with 5-Aza-CdR 2.00 micromol/L,92. 7% tumor cells stopped at S phase and G, phase cells were increased gradually with time. CONCLUSION: DNA promoter hypermethylation is associated with SHP-1 gene silence in Daudi lymphoma cell line. 5-Aza-CdR could effectively cause demethylation and inhibit the growth of tumor cell by reactivating the gene transcription. PMID- 17343199 TI - [Study on proliferation inhibiting and apoptosis inducing effects of cerulenin on multiple myeloma cells]. AB - OBJECTIVE: To determine whether fatty acid synthase (FAS) is expressed in human multiple myeloma( MM) cells and investigate the proliferation inhibition effect of fatty acid synthase inhibitor cerulenin on multiple myeloma cell line U266 and its mechanism. METHODS: FAS mRNA expression in human MM cell line U266, RPMI8226 cell was assayed by RT-PCR. The proliferation inhibition rate of U266 cells was assayed by MTr analysis. Cell apoptosis and cycle distribution were evaluated by flow cytometry (FCM). RESULTS: FAS mRNA was highly expressed in human multiple myeloma cell lines as compared with healthy donor PBMNCs. After U266 cells were treated with cerulenin (the concentrations from 5 microg/ml to 640 microg/ ml) for 24 h, the cell proliferation was markedly inhibited with a dose related manner, while the inhibition rate of human skin fibroblast cells were all lower than 30%. When U266 cells were treated with 20 pjg/ml cerulenin for 12 h and 24 h, the early apoptosis rate revealed by Annexin V/PI were 56. 9% and 69. 3% respectively, being higher than that of the blank controls (4. 3% and 1.8%, P < 0. 01). Cell cycle analysis showed it was blocked in S phase. Conclusion FAS is highly expressed in human MM. Cerulenin could induce apoptosis and inhibit proliferation of U266 cells. FAS might be a new potential target for multiple myeloma treatment. PMID- 17343200 TI - [Biodistribution study of 131I-gM-CSF in SCID mice bearing human leukemia]. AB - OBJECTIVE: To investigate the biodistribution of 131I-GM-CSF in SCID mice bearing human AML in vivo. METHODS: The xenograft model of human leukemia was established in SCID mice. In the leukemia mice, the biodistribution of 131I-GM-CSF produced by chlo amine-T method was studied. RESULTS: (1)The inoculated HL-60 cells could grow in SCID mice, which developed leukemia after 4 weeks. (2) 131 I-GM-CSF was concentrated in spleen, bone marrow and tumor tissue of the mice. In spleen and bone marrow, 131 I-GM-CSF was uptaken to peak in 30 minutes after injection, the up taking rate was (442. 9+/-86. 4) % ID/g and (4283. 8+/-252. 8)% ID/g, respectively, and maintained on higher level in 24 hours. The injection of 131I resulted in an even distribution in the whole body. CONCLUSIONS: 131 I-GM-CSF is able to concentrate electively in spleen, bone marrow and organs infiltrated by leukemia cells. The biodistribution of 131I-GM-CSF in the leukemia mice is tissue specific. PMID- 17343201 TI - [Combination of interphase- and metaphase-fluorescence in situ hybridization to identify 11q23/MLL abnormalities in acute leukemia patients]. AB - OBJECTIVE: To explore a rapid, sensitive and effective method for identifying 11 q23/MLL gene rearrangements and investigate the incidence and clinical features of adult acute leukemia (AL) patients with 11 q23/MLL abnormalities. METHODS: Bone marrow samples from 112 adult AL patients were prepared by short-term (24 hours) unstimulated culture, and karyotyped by R-banding. The abnormal signals were screened by interphase- fluorescence in situ hybridization (FISH) with dual color break-apart 11 q23/MLL-specific probe, and the 11 q23/MLL gene rearrangements were determined by metaphase-FISH. RESULTS: Of the 112 patients,9 (8. 0%) with 11q23/MLL translocations were revealed by FISH, among which only 4 (3. 6% ) was revealed by CCA. Three patients were reported by CCA to have del( 11) ( q23) , while by FISH assay two of them were 11 q23/MLL translocation and one was true deletion of I lq23 telomeric terminus. Furthermore by FISH assay II q23/MLL translocations were identified in one each patient with normal karyotype, with 11 q + and without overt 11 q23 abnormality. Eight patients with MLL gene amplification including polysome, homogenous staining region (hsr) and double minute chromosome (dmin) were also disclosed by FISH. AL patients with 11 q23/MLL abnormalities were frequently diagnosed as pro-B acute lymphoblastic leukemia (pro-B ALL) ,acute monocytic leukemia (AMoL) or biphenotypic acute leukemia (BAL). CONCLUSION: FISH with dual-color break-apart I q23/MLL -specific probe is a rapid and sensitive method to detect 11 q23/MLL abnormalities, as compared with CCA. FISH also effectively discloses translocations and amplifications involving 11 q23/MLL,and should be performed in patients diagnosed as pro-B ALL,AMoL or BAL, with CCA normal karyotype. PMID- 17343202 TI - [Identification of fetal nucleated erythrocytes in maternal blood using short tandem repeat typing after primer extension preamplification]. AB - OBJECTIVE: To develop a method for identifying fetal nucleated erythrocytes (NRBCs) in maternal blood. METHODS: NRBCs in maternal blood were detected by benzidine staining and collected by micromanipulation. After primer extension preamplification (PEP) of the entire genome from a single NRBC, short tandem repeat (STR) genotype was analysed after further amplification of this gene. Single NRBC was differentiated as fetal or maternal origin by comparison of STR genotype of NRBC with its corresponding parents. RESULTS: NRBCs were found in all of 28 pregnant women in a range of 4 to 13 per 5 ml venous blood. About 43. 6% of NRBCs were determined to be fetal origin by STR typing. CONCLUSION: This method provides effective identification of fetal NRBCs and allows non-invasive prenatal genetic diagnosis using single fetal NRBC. PMID- 17343203 TI - [The application of single-cell gel electrophoresis to the diagnosis of fanconi anemia]. AB - OBJECTIVE: To explore the feasibility of single-cell gel electrophoresis (SCGE) as one of lab tests to examine DNA breakage for the diagnosis of Fanconi anemia (FA). Case Record A 4-year-and-10-month old boy presented with cryptorchism, deformities of both thumbs and esotropia of right eye. He developed thrombocytopenia and anemia when he was 3 year- and -2-month old. He was clinically diagnosed as FA. METHODS AND RESULTS: DNA breakage of peripheral white blood cells from the patient and his parents was examined with SCGE. The percentages of cells with chromosome breakage (comet-tail positive cells) were 100%, 90% and 52% for the patient,his father and mother, respectively, while that were only 2% and 5% in two normal same-age children (P <0. 001). The micronucleus positive lymphocytes was 6.74% in the patient, being also much higher than normal value (0.40%). CONCLUSION: SCGE disclosed DNA breakage in the patient with FA, suggesting that it could be used as a test for determining DNA breakage of FA. PMID- 17343204 TI - cDNA cloning of hamster angiotensin-converting enzyme and mRNA expression. AB - Angiotensin-converting enzyme (ACE; EC 3.4.15.1), a dipeptidyl carboxypeptidase, converts angiotensin I to angiotensin II, the central product of the renin angiotensin system. We here report molecular cloning of the complete open reading frame (ORF) of hamster somatic-type ACE and its expression in hamster organs. The cloned cDNA comprises an ORF of 3942 bp, which encodes 1314 amino acids of the precursor protein of hamster somatic ACE. On the deduced amino acid sequence a putative signal peptide and a transmembrane segment are predicted at the N terminus and near the C-terminus, respectively. Two homologous domains, referred to as N- and C-domains, are present within somatic ACE, and within each of the homologous domains a putative active center is found, as has been the case in human, mouse, rat and rabbit. The similarity of the hamster sequence with the sequences of these other mammals at both the nucleotide and amino acid levels is high (above 83%). mRNA expression analysis by conventional polymerase chain reaction (PCR) shows wide distribution of the transcript, with dominant expression in lung and kidney. Quantitative analysis of mRNA expression demonstrates that levels in lung and kidney are 100-1000 times higher than in the other organs, suggesting that these organs are important in the hamster renin angiotensin system, as they are for other mammals. PMID- 17343205 TI - Molecular cloning and characterization of Bombyx mori sterol carrier protein x/sterol carrier protein 2 (SCPx/SCP2) gene. AB - Cholesterol transport is a very important process in insect. We have isolated the Bombyx mori sterol carrier protein x (BmSCPx) cDNA and sterol carrier protein 2 (BmSCP2) cDNA: a 1.7 kb clone encoding SCPx, a 3-ketoacyl CoA thiolase, and 0.6 kb clone presumably encoding SCP2, which is thought to be an intracellular lipid transfer protein. Interestingly, the identical gene SCPx/SCP2 encodes the two types of transcripts by alternative splicing mechanism in Bombyx mori. The SCPx mRNA spans two exons in genome, and conceptual translation of the SCPx cDNA encodes a protein of 536 amino acids, which contains a thiolase domain and a SCP2 domain. Whereas the SCP2 mRNA partly lakes the first exon, and the SCP2 is a 146 amino acids containing a SCP2 domain only. Both BmSCPx and BmSCP2 have a putative peroxisomal targeting signal in the C-terminal region. BmSCPx shares 94 and 72% similarity to Spodoptera littoralis SCPx and human SCPx, respectively. RT-PCR analysis reveals that transcripts of BmSCP2 were detected in all tissues analyzed. BmSCPx transcription expressed only in midgut and malpighian tubules. However, the BmSCPx and BmSCP2 express strong in midgut during the last instar larvae. The tissue-specific expression pattern of BmSCPx and BmSCP2 is consistent with a role for these proteins in cholesterol metabolism. The results suggest that SCPx/SCP2 may play a key role in sterol absorption and intracellular carrier in silkworm. PMID- 17343206 TI - Isolation and characterization of a class III homeodomain-leucine zipper-like gene from Gossypium barbadense. AB - Class III homeodomain-leucine zipper (HD-Zip III) genes are important plant specific transcription factors which have key roles in different stages of vascular and interfascicular fiber differentiation. A novel HD-Zip III gene, designated GbHB1, was isolated by suppression subtraction hybridization and RACE (rapid amplification of cDNA ends) from Gossypium barbadense (sea-island cotton). The GbHB1 cDNA has a total length of 3061 bp with an open reading frame of 2508 bp, encoding a predicated polypeptide of 836 amino acids with a molecular weight of 91.6 kDa and a calculated pI of 5.93. The putative polypeptide of GbHB1 is structurally characterized by a homeodomain positioned adjacent to a leucine zipper domain, which shares high identity with other reported HD-Zip III domains. DNA gel blotting analysis shows that GbHB1 is a low-copy gene. Organ expression pattern analysis reveals that GbHB1 expressed highly in ovule and stem, followed by in root, and low in leaf and cotyledon. The result suggests that GbHB1 may play a regulatory role in cotton interfascicular fiber development. PMID- 17343207 TI - Characterization and function analysis of a cold-induced AmCIP gene encoding a dehydrin-like protein in Ammopiptanthus mongolicus. AB - A cDNA clone was isolated after difference screening from cotyledons of two-week cold-treated Ammopiptanthus mongolicus. The full-length cDNA sequence [designated as AmCIP (A. mongolicus cold-induced protein) gene] was 806 bp long and contained a 465 bp open reading frame (ORF) encoding a 16.6 kD protein of 154 amino acids. Bioinformatic analyses indicated that CIP belongs to dehydrin family with the features of high hydrophilicity, a helix K-segment, a long Gly-rich region and a phosphorylatable tract of Ser as well as deficiency in Cys and Trp. The expression of CIP gene increased after two weeks of cold treatment and more expression was detected in radicle than in cotyledon. And PCR amplification of the AmCIP gene from genome of A. mongolicus revealed this gene has no intron. Function prediction suggested this protein seems to protect the stabilization of membrane structure and prevent macromolecular coagulation or sequestrate calcium ions by association or disassociation with membrane under low temperature conditions. PMID- 17343208 TI - Porcine granulin gene (GRN): molecular cloning, polymorphism and chromosomal localization. AB - GRN has been shown to have roles in multiple processes involved in cell growth, development and wound repair in rodents and humans. We have isolated the full length cDNA of GRN gene encoding porcine granulin protein by in silico cloning, RT-PCR and RACE. The deduced amino acid indicated 71.5% identity with the corresponding human sequence and the seven and one-half granulins showed highly conservative between pig, human and murine. A single nucleotide substitution resulting in the amino acid change (ATG/Met --> TTG/Leu) was detected within exon 5. Allele frequencies in six pig breeds showed distinctive differences between those Chinese indigenous pig breeds and European pigs. Using the IMpRH panel, we mapped the porcine GRN gene to porcine chromosome 12p11-p13. Our data provide basic molecular information useful for the further investigation on the function of GRN gene. PMID- 17343209 TI - Cloning and characterization of cotton GhBG gene encoding beta-glucosidase. AB - Beta-1,4-glucosidase (BG, EC3.2.1.21), one of three cellulases, is a widespread family of enzymes involved in the metabolism of cell wall polysaccharides in both prokaryocytes and eukaryotes. Here, we report the isolation of a full-length cDNA encoding beta-1,4-glucosidase protein (designated as GhBG) and its putative function in the process of fiber development and in yeast. Through random sequencing of the cotton fiber cDNA library from 7235 germplasm line, with elite fiber quality in Gossypium hirsutum L. and utilizing the 5' rapid amplification of cDNA ends (RACE) technique, a 2133 bp cDNA clone encoding a cotton fiber specifically expressed protein (accession number: DQ103699) was isolated. GhBG was composed of a 1884 bp open reading frame (ORF) encoding 627 amino acid residues. This putative protein had an isoelectric point of 8.17, a calculated molecular weight of 68.78 KD and a signal peptide with 23 amino acid residues at the N-terminal. RT-PCR analysis indicated GhBG was specifically expressed in fiber cells and was highly abundant in 5-17 day post anthesis (DPA). It was not, however, expressed in root, hypocotyls or leaves. Southern blotting analysis showed there were two copies of GhBG in the upland cotton genome; most likely contained in sub-genome A and sub-genome D. GhBG was then integrated into a yeast expression vector, pREP-5N and electro-transformed into fission yeast Schizosaccharomyces pombe Q-01. The results demonstrated that GhBG led to a significant increase in cell length and width and a remarkable decrease of the length/width ratio. Compared to vector control transformants, cells were significantly larger and rounder and their growth velocity was also reduced. PMID- 17343210 TI - Tandem and single genes of three membrane-bound nitrate transporters in the nar gene cluster of the moderately halophilic denitrifier, Halomonas halodenitrificans. AB - We identified the genes encoding the membrane-bound nitrate reductase (Nar) from the moderate halophile, Halomonas halodenitrificans, and examined the structure of the gene cluster. Screening of a H. halodenitrificans genomic DNA library in lambda EMBL3 phage by chromosome walking revealed that the region adjacent to the nor gene cluster encoding nitric oxide (NO) reductase contains three nitrate transporters: tandem narK2 and narK1.1 genes and a single narK1.2 gene encoded in opposite directions. NarK1.1 and NarK1.2 proteins, which have 12 putative membrane-spanning helices, were classified as type I NarK, whereas NarK2, which has 14 putative membrane-spanning helices, was classified as a type II NarK. NarK1.1 and NarK2 proteins were considered to be functionally and structurally linked in the cytoplasmic membrane. The systems regulating the expression of the tandem narK2K1.1 gene and the single narK1.2 gene were found to be different. Further, binding sites for NarL and Fnr-like proteins are present in the promoter region of the narK2 gene. PMID- 17343211 TI - Identification of two genes encoding the major light-harvesting chlorophyll a/b proteins of photosystem II in green alga Dunaliella salina. AB - Dunaliella salina is a useful model for studying the respective roles of each LHCII protein at the molecular level in extreme environmental conditions. However, information about the LhcII genes in D. salina is very limited. In order to identify more LhcII genes in D. salina, two additional LhcII cDNAs were obtained by screening a cDNA library. The genomic DNA was amplified by PCR using a specific primer set corresponding to the 5' and 3' untranslated regions of each transcript. The untranslated regions of the two additional genes are obviously different from each other; therefore they are two genes. Each gene contains an open reading frame for a protein of 253 amino acids. The two deduced proteins in D. salina are 99% identical at the amino acid sequence level to the previously reported LHCII protein in the same genus D. tertiolecta. Unrooted phylogenetic tree showed that types of LHCII proteins in D. salina did not correspond to any types in C. reinhardtii. PMID- 17343212 TI - Evolutionary divergence of the pre-promotor region of ribosomal DNA in the great apes. AB - The human ribosomal intergenic spacer (rIGS) differs considerably on nucleotide sequence and regulatory elements positioning from their counterparts in the mouse, rat and Xenopus laevis. In the present study, we have PCR amplified, cloned and sequenced the rIGS fragments of about 4.5 kb length, located approximately 2 kb upstream of the rRNA transcription start point for the great apes, Pan paniscus, Pan troglodytes, Gorilla gorilla and Pongo pygmaeus. Alignment of the primates' orthologic nucleotide sequences reveals high extent of similarity, with the exception of highly repetitious region between the two Alu repeats, nearest to the onset of transcription. Data obtained have been analyzed for further understanding of the evolution of repetitive sequences. We have also shown, that MARs/SARs distribution patterns in the pre-promoter rIGSs of the great apes and the mouse are surprisingly similar in spite of an absence of similarity in the primary structure and regulatory elements organization in the region under study. PMID- 17343213 TI - Mutation analysis of the natriuretic peptide precursor B (NPPB) gene in patients with hypertrophic cardiomyopathy. AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetically heterogenous disease caused by mutations in genes that primarily encode sarcomeric proteins. No mutation is identified in up to 40% of HCM patients, suggesting other causative genes exist. Natriuretic peptide precursor B (NPPB; also known as "BNP") is a cardiac hormone involved in body fluid homeostasis and cardiac myocyte growth. NPPB concentrations are markedly increased in patients with ventricular hypertrophy, and it is therefore possible mutations in the NPPB gene could cause HCM. METHODS: Genomic DNA was extracted from peripheral blood in 238 consecutive probands with HCM. The coding regions and intron/exon boundaries in the NPPB gene were amplified by PCR, and products were screened for sequence variants using high-performance liquid chromatography, followed by direct DNA sequencing. RESULTS: Four sequence variants in the NPPB gene were identified in 9 of the 238 probands screened. Two of the variants were intronic, one was a synonymous variant at codon 79, and the final variant resulted in an amino acid substitution from arginine to histidine at codon 47 (Arg47His). The Arg47His variant was identified in a control population consisting of 204 chromosomes at an allelic frequency of 0.5%, and is therefore unlikely to cause disease. CONCLUSION: No disease causing mutations were identified in the NPPB gene in this cohort, indicating that mutations in this gene are unlikely to be responsible for HCM. PMID- 17343214 TI - Single tube genotyping of GSTM1, GSTT1 and TP53 polymorphisms by multiplex PCR. AB - Glutathione S-transferases (GST) are enzymes involved in the conjugation of a number of human carcinogens, while p53 tumour suppressor gene is the most frequently mutated gene identified till now in human neoplasias. Typically, GSTM1 and GSTT1 genotyping are performed together, with several different protocol described and sometimes with the risk of misclassification due to "false negative", depending on the internal positive control employed. Here, we report a modification of the classical multiplex polymerase chain reaction (PCR) method, allowing the genotyping of GSTM1, GSTT1, together with a polymorphism within the intron 3 of TP53 tumour suppressor gene (a 16 base pairs (bp) duplication) in a single tube, with an appropriate internal positive control. To test the applicability of the method, the frequencies of the deleted alleles of GSTM1 and GSTT1 (null genotypes), and the 16 bp duplication of TP53 gene were assayed in a series of Caucasian DNA samples. PMID- 17343215 TI - Current epidemiology of leprosy in India. PMID- 17343216 TI - Global leprosy statistics: a cause for pride, or frustration? PMID- 17343217 TI - Promoting early detection in leprosy--a literature review to identify proven and potential interventions addressing patient-related delay. AB - OBJECTIVES: The objective of the literature review was to identify proven and potential interventions to promote early diagnosis and start of treatment in leprosy, specifically, forms of intervention addressing needs at the local or primary level. DESIGN: Using a structured search procedure, we identified recent leprosy-related publications describing proven interventions. To identify potential interventions the search was extended to publications assessing knowledge and attitudes towards leprosy and extended again to identify publications relating to patient-related delay in the context of other infectious diseases. RESULTS: The review identified just 19 publications reporting leprosy related interventions that included a form of evaluation of which only 10 directly addressed patient-related delay. These included health education interventions focussed on people directly affected by leprosy, their family members and other key individuals or groups within the local community. We identified no reports of interventions focussed specifically on the needs of women. CONCLUSIONS: Our conclusion is that the evidence base available to inform the choice of small-scale interventions to promote early detection at the primary level is extremely limited. There is an urgent need to develop and extend the range of proven interventions, specifically those that address the needs of women, those that explore and develop the health promotion potential of people previously affected by,leprosy and those that exploit the potential of individuals with leadership roles within the community. This will require careful attention to planning, implementation, evaluation and reporting of interventions. PMID- 17343218 TI - Appraisal of skin smear reports of field laboratories. PMID- 17343219 TI - Re-enablement of the neurologically impaired hand--1: terminology, applied anatomy and assessment. Report of a surgical workshop held at Green Pastures Hospital and Rehabilitation Centre, November 2004, Pokhara, Nepal. PMID- 17343220 TI - Re-enablement of the neurologically impaired hand--2: surgical correction. report of a surgical workshop held at Green Pastures Hospital and Rehabilitation Centre, November 2004, Pokhara, Nepal. AB - The last half-century has seen tremendous advances in the surgical treatment of neuropathic conditions of the hand. Many of these procedures give clear benefit to patients and have been established by clinical practice and well-formulated assessment. However, much remains to be discovered, especially with respect to which procedures should be used on which hands, and the impact of various procedures on the ability to carry out activities of daily living. Increased communication between the 'West', where funding is available for well designed trials and where reference textbooks are usually published, and the 'East', where the surgery is most commonly performed, will undoubtedly lead to an even better understanding of the treatment of the neuropathic hand. PMID- 17343221 TI - Association between anti-pGL-I IgM and clinical and demographic parameters in leprosy. AB - OBJECTIVE: To determine the risk factors and clinical significance of anti-PGL-I seropositivity. DESIGN: A large-scale sero-epidemiological study (COLEP) was carried out in northwest Bangladesh. Blood on filter paper from 1025 newly diagnosed patients was collected before treatment was started and tested with an anti-PGL-I ELISA; the relation between patient determinants and seropositivity was calculated using logistic regression. RESULTS: The median age was 30 years and the male:female ratio 1.9. Overall, 342 patients (33.4%) were seropositive. The following determinants showed a significant correlation with seropositivity (P < 0-05) in multivariate analysis: sex, age, disability grade, bacterial index and classification according to the World Health Organization (WHO) system. The number and extent of clinical signs correlated with seropositivity, except for the presence of satellite lesions. People with or without a BCG vaccination scar had a similar risk to be seropositive. CONCLUSION: Serology is a marker for a higher systemic bacterial load and may identify potential infectious sources among patients with few clinical signs. The size of skin lesions was positively correlated with seropositivity. We did not find different levels of seropositivity among patients with one or two skin lesions, neither did we find different levels among patients with or without satellite PMID- 17343222 TI - The relationship between detection delay and impairment in leprosy control: a comparison of patient cohorts from Bangladesh and Ethiopia. AB - INTRODUCTION: It is acknowledged that longer delays between first symptoms and diagnosis result in increased impairment in newly detected leprosy patients. However, it is unclear whether detection delay in relation to impairment can be used as a general or absolute performance indicator of leprosy control programmes. It is unknown whether similar delays always result in similar proportions of impairment. Therefore, the present study examined the quantitative relationship between delay and impairment in two different patient populations. METHODS: Patients from two study cohorts (BANDS and AMFES) who reported voluntarily were included in the analysis. Data on detection delay, WHO impairment status, type of leprosy, age and sex were analysed using descriptive statistics and multivariate logistic regression analysis to identify significant risk factors for impairment and to quantify the relationship between detection delay and impairment status at intake. RESULTS: Detection delay was an independent risk factor for impairment at presentation in multivariate analysis. The AMFES cohort reported more impairment at detection than BANDS. In multivariate analysis, this difference was significant among PB patients (51% in AMFES versus 15% in BANDS), but not in MB patients (56% in AMFES versus 45% in BANDS). In fact, for every delay category PB patients from AMFES had much higher proportions of impairment than PB BANDS patients. Impairment rates in MB patients from AMFES were higher in every delay category, but the differences between the two cohorts were much smaller compared to PB patients. CONCLUSIONS: Our analysis confirms earlier findings that with longer delays, the risk of impairment at presentation increases. With the same reported delay, however, the proportion impaired can vary considerably between different patient populations, in particular for PB leprosy. Delay can therefore not simply be used as a general or absolute performance indicator for programme evaluation. Achieving short delays remains important in general, but understanding and addressing the underlying mechanisms of delay specific to a patient population adds substantially to the effectiveness of leprosy control. PMID- 17343223 TI - Isolation of mycobacterium leprae from untreated borderline tuberculoid, mid borderline and indeterminate cases using the mouse foot pad technique--a study of 209 cases. AB - Using the mouse foot pad (MFP) system, isolation of Mycobacterium leprae was attempted in 209 skin biopsies obtained from 114 borderline tuberculoid (BT), 62 mid borderline (BB) and 33 indeterminate (1) untreated cases. Unequivocal growth in the foot pads of mice was seen in 100 (47.8%) cases. Of these 100 cases that showed growth in the mouse foot pad system, in 20 cases acid fast bacilli (AFB) were detected in small numbers (1 + ) in either smear or homogenate. The remaining 80 (42%) cases were negative for AFB in both smear and homogenate. The occurrence of viable bacilli and percentage take at 12 months was highest in BB (76 and 86%) followed by BT (38 and 75%) and I (30% and 52%) cases. In most of the BT (65%) and I (60%) cases, the first peak was seen only at 12 months. These results confirm that viable bacilli can be isolated and expanded from a good proportion of negative BT-BB cases using immunocompetent Swiss White mice. PMID- 17343224 TI - Inter-observer reliability in assessment of sensation of skin lesion and enlargement of peripheral nerves in leprosy patients. AB - The accurate diagnosis of leprosy is important to both individuals and to the community. The diagnosis of leprosy is based on clinical examination. However, the reliability of clinical assessment of sensation in skin lesions and thickness of peripheral nerves on palpation has not been well studied, due to the lack of a gold standard. We report an inter-tester reliability study of the clinical assessment of skin lesions and thickness of ulnar and popliteal nerves in leprosy patients by different staff. For sensory testing of skin lesions, the agreement between the leprologist and leprosy control staff, and between one student and leprosy control staff, was poor (kappa values < 0-4). The agreement between the leprologist and the two students, between the two students, and between the other student and local leprosy control staff were fair (kappa values > 0.4, but < 0 6). For the palpation of ulnar and popliteal nerves, the agreement ranged from 0.36 to 0.52 and from 0.02 to 0.29 in different pairs of testers, respectively. The reliability of clinical diagnostic skills based on both sensory testing of skin lesions with the cotton wool method and palpation of superficial peripheral nerves was unsatisfactory. PMID- 17343225 TI - Indeterminate leprosy in an infant. AB - An infant, 8 months old having histologically confirmed indeterminate leprosy is reported. The source of infection and possible mode of transmission are discussed. PMID- 17343226 TI - Magnetic resonance imaging of ulnar nerve abscess in leprosy: a case report. AB - A 14-year-old girl on multidrug treatment for borderline tuberculoid leprosy presented with a swelling in her left arm and soon thereafter developed an ulnar claw hand. MRI showed a well-defined ovoid lesion arising from the left ulnar nerve, isointense to muscle on T1W images and hyperintense on T2W and STIR images. On post-gadolinium T1W sequence, the lesion showed peripheral rim enhancement with central necrosis suggestive of abscess. The ulnar nerve proximal and distal to the lesion was thickened and showed mild contrast enhancement. On aspiration the swelling yielded frank pus which was positive for acid-fast bacilli. PMID- 17343227 TI - Iris in an HIV seropositive leprosy patient. PMID- 17343228 TI - Use of virtual reality simulator in the training of postgraduated surgical residents. AB - AIM OF THE STUDY: The purpose of this research project, granted by the Italian University and Scientific Research Ministry (MIUR) and carried on among four Surgical Departments in Padua, Verona, Pisa and Rome-Tor Vergata Universities, is to study the effectiveness of a virtual reality simulator as a tool for surgical residents training and as a method for measuring the surgical skills. MATERIALS AND METHODS: The residents performances on the computer were compared with those obtained by other training groups: medical students with no surgical background, senior surgeons with experience in the laparoscopy field and non medical students with referred ability in videogames. The residents were also sent to a well certified live animal laboratory where they could perform a cholecystectomy in a pig. Their operation was assessed by two independent observers using a new scoring methods for assessing the operative errors. RESULTS: Statistically significant differences among the groups could be seen only after several tasks sessions and in the more surgical specific tasks. The first data analysis shows a fair correlation between the residents rank positions after the training tasks on the simulator and those obtained in the surgical operation. CONCLUSION: Even if the data are not conclusive and the surgical simulators must develop greater levels of fidelity and operational diversity, the potential value of simulation in the educational surgical field appears to be impressive. PMID- 17343229 TI - [Hashimoto thyroiditis. Possible cause or consequence of a malignant thyroid tumor]. AB - AIM OF THE STUDY: The Authors performed a retrospective study on their case records in order to analyze the epidemiological aspects of association between Hashimoto thyroiditis and differentiated thyroid carcinoma. MATERIALS AND METHODS: From January 2004 to December 2005 the Authors performed 282 total thyroidectomy for any thyroid pathology. All patients were studied preoperatively even dosing antithyroid antibodies. In the study are included patients who presented histological finding of both Hashimoto thyroiditis and carcinoma. RESULTS: Eleven patients (23.9%) of 46 patients operated on for differentiated thyroid carcinoma also presented histological finding of thyroiditis. Association of thyroiditis and carcinoma was present in 39.2% of histologically detecied thyroiditis (28 patiems). CONCLUSIONS: Pathophysiological relationship between Hashimoto thyroiditis and DTC are still unclear, although a certain association of theese two anatomo-clinic entity has been demonstrated. We can't yet say if Hashimoto thyroiditis advance and facilitale tumour arising or thyroiditis is a reaction to neoplasia or these two pathologies are indipendeni each other, although both are present in the same patient. PMID- 17343230 TI - [Methods of intraoperative localization in the surgery treatment of persistent and recurrent secondary hyperparathyroidism]. AB - The intraoperative localization of residual parathyroid tissue during re operations for persistent or recurrent secondary hyperparathyroidism (HPT) could have difficult due to cicatricial phenomena, anatomic modifications, ectopic or super-numerous glands. The use of intraoperative localisatin methods, as ultrasonographic and gamm-camera, permits a great level of success in identifying residual gland tissue. The Authors report their experience in the treatment of 5 cases of persisten HPT and 3 cases of recurrent HPT using gamma-camera and ultrasonography intraoperatively. Gamma-camera presented a sensitivity of 88% while ultrasonography did 100%. According to the experience, even numerically limited, of the Authors, intraoperative ultrasonography offers better results than gamma-camera, with less technical complexity. PMID- 17343231 TI - [Esophageal perforation: analysis of seven cases treated by early surgical treatment with good functional results]. AB - INTRODUCTION: Esophageal perforation has been considered a catastrophic and often life-threatening event, with very high mortality rates. Most of the cases are due to a complication in endoscopic manouvers and the best treatment, conservative rather than aggressive, remains a controversial topic. MATERIAL AND METHODS: In 1995-2005 period we observed 7 cases of esophageal perforation, 5 women and 2 men mean age 73.2 y (range 60-87). Three cases are due to foreign body ingestion, 2 cases to endoscopic manoeuvres, 2 cases were spontaneous. In 3 cases the lesion was in the cervical tract of the esophagus, in the thoracic tract the others. All the patients were admitted very early to our Unit and presented disphagia, vomiting and dyspnoea, 2 out of them also a pleural effusion. In iatrogenic perforation we performed a cervicotomy and a drainage of mediastinic abscess, while in spontaneous lesions mono (one case) or bipolar esophageal exclusion (one case) with primary suture, jujunostomy and drainage of pleural effusion were the treatment. In foreign body perforation we performed thoracotomic and cervicotomic esophagotomy, extraction of the foreign body, direct suture with pleural or muscle protection. We didn't observe any intra or post-operative mortality. About the complications, we observed a bilateral pleural empyema, a chylous fistula, a digestive bleeding due to gastric ulcer, a laparotomic infection, a parossistic FA and a persistent esophageal fistula. Mean hospital stay was 24.3 days (range 10-43). All the patients were discharged to the hospital in good conditions. CONCLUSIONS: In conclusion in most of the cases of esophageal perforation the surgical treatment is the treatment of choice for its lower morbidity and mortality and good functional results. PMID- 17343232 TI - [Different approaches for medical or surgical management of Crohn's disease: the importance of the classification of Vienna]. AB - The Vienna classification of Crohn's disease provides defined criteria for a phenotypic classification of the disease, considering that phenotypic parameters reflect the contribution of both genetic and environmental factors to the expression of disease. The classification includes mainly three criteria as part of the natural course of disease: age at the diagnosis, location and behaviour and it provides distinct definitions to categorize Crohn' patients into 24 subgroups. In this study we attempt to define the clinical importance of the Vienna classification and the possibility to optimize medical care of Crohn's disease according to patient subgroups. Early age at the diagnosis is associated with a greater prevalence of a family history, greater small bowel involvement, more complicated stricturing disease and a higher frequency of surgery. Surgery is based on exact knowledge of location: L1 patients might profit the most from resective surgery, L4 patients from strictureplasty. Stricturing behaviour (B2) might be the most appropriate subgroup for surgical treatment. Penetrating behaviour (B3) is confirmed as an important risk for early postoperative recurrence; patients in the penetrating behaviour group (i.e. fistulas) have a specific indication for immunosuppressive or anti-tumour necrosis factor-alpha therapy. PMID- 17343233 TI - [Timing and results of the surgical treatment of the diverticular disease of the colon]. AB - AIMS: To evaluate retrospectively the outcome of the curative open and laparoscopic surgical approach to the diverticular disease according to timed steps based on the pathologic stage. PATIENT AND MATERIAL: From 1989 83 out of 242 outpatients underwent surgery in emergency or after medical failure and at least two acute attacks requiring hospital admittance, or complicated diverticulitis. Modified Hinchey classification staged the disease. Clinic and instrumental criteria, surgical procedures, early and late complications were statistically evaluated (Students t-test and exact Fischer test, p < 0.05) in comparison with the different steps of therapeutic strategy. RESULTS: Twenty nine patients were classified as Hinchey 0, 26 as I, 14 as II, 11 as III, 3 as IV. Clinical characteristics of the lap and open groups overlapped, with higher rate of earlier age in first and advanced stages in the second group. 16 patients (19.3%) underwent surgery at the first attack in emergency or in delayed emergency (5 TC-guided drainages). 30 open and 53 lap procedures were done: 21 two-stage: 18 primary resections + ileostomy and 3 Hartmann; 61 single stage: 49 sigmoidectomy, 12 left colectomy. 4 conversions (7.5%), 12 early (14.5%) and 10 late (12.1%) complications were observed. DISCUSSION: Complications rate was higher in the open group including more advanced stages. Elective surgery performed following conservative therapy, 4 weeks from the first acute attack in younger people (age < 55yrs.) and after two attacks in elder (age > 55yrs.) showed a significant lower complications' incidence (p < 0.05) compared to the 8 weeks delayed operations. CONCLUSION: Surgery of diverticulitis must follow standardized criteria. The laparoscopic approach could be performed in more severe stages, provided that conditions of delayed emergency were achieved. PMID- 17343234 TI - [Effectiveness of contemporary injection of botulinum toxin and topical application of glyceryl trinitrate against postoperative pain after Milligan Morgan haemorrhoidectomy]. AB - PURPOSE: After haemorrhoidectomy the maximum resting pressure (MRP) of the anal canal is significantly increased. This increase play an important role in the making of postoperative pain. Recently, both the topical application of glyceryl trinitrate (GT) and the intrasphincter injection of botulinum toxin (Tox), resulted effective, in reducing temporary the MRP although with different mechanism of action. In this study the effectiveness and safe of contemporary injection of Tox and topical application of 300 mg/die of GT after Milligan Morgan haemorrhoidectomy, were evaluated. MATERIALS AND METHODS: Ten patients, undergoing Milligan-Morgan haemorrhoidectomy for 3rd and 4th degree haemorrhoids are included in this study. In all subjects, preoperatively and after 5 and 40 day following surgery, an ano-rectal manometry was performed. At the end of surgery, in all patients, 0.4 ml of solution containing 20UI of Tox was injected and 100 mg of 0.2% of GT was applied in the anal canal and in the perianal wounds. Afterwards the patients has been instructed to apply 100 mg of GT three times daily, for seven days. Time of perianal wounds healing, of first defecation, to return to work, of duration of surgery, of hospital stay, the complications, postoperative pain either on resting or during defecation, the analgesic consumption and side effects were recordered. RESULTS: On the 5th and 40th postoperative day, the MRP resulted significantly reduced as compared to preoperative values. Postoperative pain either on resting or during defecation was higher on the 1st assessment, afterwards it progressively decreased. Anal incontinence was observed only in two patients, whereas headache only in one case. CONCLUSIONS: The contemporary intrasphincter injection of Tox and perianal application of 300 mg/die of GT is safe and effective, with an incidence of complications similar to those detected when this drugs are given alone. PMID- 17343235 TI - CASTLE tumour of the thyroid. Value of multiplanar imaging acquisition. AB - BACKGROUND AND OBJECTIVE: Thyroid carcinomas thymus-like differentiation (CASTLE) are rare. The aim of this paper is to address a valid diagnostic and therapeutic protocol for these tumours using three exemplary cases and the previously published literature. METHODS: The routine use of Magnetic Resonance Imaging (MRI) in all cases of unclear thyroid fine needle aspiration cytology (FNAC) or in cases of multiple neck masses. RESULTS: Three cases of thyroid CASTLE tumours, finally confirmed by histology, are evaluated. All three patients remain in good conditions after an aggressive surgical approach followed by radiotherapy. CONCLUSIONS: MRI should be routinely used in cases of unclear FNAC or multiple neck masses, Surgery and radiotherapy are effective to manage thyroid CASTLE tumours. PMID- 17343236 TI - [An unusual cause of small bowel obstruction in the elderly]. AB - Paraduodenal hernia is an unusual form of internal hernia that results from a congenital midgut malrotation. It is classified as either right or left, depending on anatomic features, and embryologic origin. Left hernias are three times more common than right. Clinical symptoms may be intermittent and non specific, as nausea, distension and abdominal pain or sometimes acute small bowel obstruction or ischemia. The average age at diagnosis is usually 38 years. We report a case of right paraduodenal hernia in a 79 years old man admitted to the emergency department with an acute small bowel obstruction. PMID- 17343237 TI - A rare case of ectopic pancreas in the ampulla of Vater presented with obstructive jaundice. AB - A rare case of ectopic pancreas in the ampulla of Vater presented with obstructive jaundice. Ectopic pancreas is a common congenital disorder which is referred to as pancreatic rest. The incidence in autopsy series varies from 1 to 2% (range 0.55 to 13%). Most common site of ectopic pancreatic tissue is the stomach, although it can be found anywhere in the foregut and the proximal midgut. Ectopic pancreatic tissue in the ampulla of Vater is a very rare condition. Searching in the literature, using the terms "ectopic pancreas" and "Ampulla of Vater", we found only 10 records. The authors report on a rare case of a 69 years old female with ectopic pancreas in the ampulla of Vater, presented with painless obstructive jaundice, and the diagnostic and therapeutic strategy that followed. PMID- 17343238 TI - [Mesenteric cyst lymphangioma; a case report and literature review]. AB - OBJECTIVE: The Authors report their experience in diagnosis and treatment of one case of mesenteric cystic lymphangioma; recent international literature review. EXPERIMENTAL DESIGN: Complete clinical report. Diagnostic, clinical and prognostic indication, evaluation of effectiveness of radical surgical treatment and follow-up. SETTING: Operative Unit of General and Thoracic Surgery. University "Paolo Giaccone" of Palermo. INTERVENTION: Radical surgical treatment, according to international guide-lines. RESULTS: Complete recovery with "restitutio ad integrum". No relapse were recorded at short follow up. CONCLUSIONS: Even when asymptomatic and discovered incidentally, LCM must be treated surgically because of the potential to grow, invade vital structures, and develop life-threatening complications. The best and only radical treatment is the total removal of the lesions with microscopically clear borders, when it is available. PMID- 17343239 TI - First sternocostal degenerative arthritis with intrarticular fluid collection. A case report. AB - A rare case with clinical condition of first sternocostal degenerative arthritis with intra-articular fluid collection that developed after long-lasting intense exercise (weight-lifting) for twenty years is reported. Imaging findings and differential diagnoses of the case are presented. PMID- 17343240 TI - Osteoid osteoma of the patella. Case report and review of the literature. AB - Osteoid osteoma is a benign, bone-forming tumor. The diaphyses of the long bones are the sites of predilection (at least 50% of all cases occurring in the femur and the tibia). Also this lesion has a male preponderance and the majority of cases present in the second and third decade. We represent an unusual localization of osteoid osteoma in the patella of a 51-year old woman. PMID- 17343241 TI - [Lights and shadows in the radio-television broadcasting on medical informations]. AB - Some actual difficulties in the medical praxis, arising and growing in the social environment, and well known to the operating physicians and surgeons, should stimulate a careful analysis of the situation in search of the more likely causes and to draw the more suitable remedy. One of them certainly is the constant, and sometimes invading, presence of radio-television broadcasting in the all day life of everybody of more o less deepened programs inherent to themes of health. It is of the utmost importance to think over the topic, especially in order to evaluate the positive and negative aspects of the impact of radio and television media on the sensibility of the patients and in order to reflect on their reactions, and as a reflex on the professional behaviour of the physicians and surgeons, with all the lights and shadows. PMID- 17343242 TI - [Multiple trauma complex with abdominal prevalence]. PMID- 17343243 TI - Design of preparations for all-ceramic inlay materials. AB - Because of the developments in the field of all-ceramic materials, which have quite different material properties compared with traditional materials for prosthetic treatment, it was also important to adapt the preparation to the new circumstances. Practiced design guidelines for the restorative treatment of teeth for all-ceramic restoration are illustrated in this article. Based on traditional retentive preparation shapes, modifications of these geometries "designed for ceramics" were developed and postulated. Despite excellent 15-year long-term results, it is important to draw the appropriate conclusions from failures that have occurred. The geometry of the cavities for all-ceramic inlays must be matched much more to the material-specific properties of hard and brittle restoration materials. Cavities designed for ceramics must therefore have the simplest possible basic geometry. Because of adhesive bonding, a retentive shape of the preparation is not necessary. Previous ceramic inlay designs must be redefined to achieve an increase in the fracture resistance of the ceramic. PMID- 17343244 TI - Fast algorithm for real-time detection of root canal orifices in video images. AB - Real-time image analysis in endodontics opens new options of treatment support in dentistry. Imaging software was developed to detect the root canal orifices in video sequences of trepanated teeth acquired by a digital video microscope, the Motic DM 143. The software developed is capable of communicating with any video camera connected to it and can automatically detect almost all root canal orifices in trepanated teeth. To recognize the root canal orifices we used the so called Minimum-Distance Classification. The Minimum-Distance Classification provides a color-based pattern recognition algorithm, which is directly implemented in the function accessing the video stream, and is therefore very fast. Processing speed varied between 30 and 64 ms per image with an input image resolution of 352 x 288 pixels on the Pentium 4 computer (2 GHz). The developed software was tested in this study on 78 trepanated teeth. The mean detection sensitivity of the software found for all 78 teeth is 97.01%. PMID- 17343245 TI - Three-dimensional diagnostics, planning and implementation in implantology. PMID- 17343246 TI - Single-tooth restorative treatment using an immediate-loading CAD/CAM technique. AB - PURPOSE: Definitive restoration of missing tooth 25 in a single visit by positioning a tapered, immediately loaded implant, a titanium/zirconia abutment, and an all-ceramic crown. MATERIALS AND METHODS: Surgery was planned using a software application which processed CT scan images to obtain a 3-D virtual model. With these images, the crest height and axial orientation of the virtual implants can be reproduced from an implant analog on a working cost using the Ray Set Implant Ready-to-Load transfer procedure developed on the Ray-Set device (Biaggini Medical Devices, La Spezia, Italy). A tapered Exaca CV implant with a diameter of 4.0 mm (Biaggini Medical Devices, La Spezia, Italy) was chosen for its primary stability, an essential prerequisite for immediate loading. The all ceramic crown on the Exacta Z CAD abutment was designed and fabricated using a CAD/CAM system. CONCLUSIONS: Using a computerized method, a surgical treatment plan can be defined using a prosthetic approach to implant positioning and pre construction of a mesostructure and superstructure for chairside insertion and immediate loading, requiring only a single surgical session to obtain an excellent functional and esthetic result with superior accuracy and long-term predictability. PMID- 17343247 TI - FGP technique with Cerec 3D. AB - With the presented technique it is possible for the user of the chairside Cerec method to design the functional anatomy of the occlusal surface and the precision of the occlusal level right from the start, so that the restoration fits well in the occlusion ofthe patient without causing interference. PMID- 17343248 TI - Health economic issues in rheumatoid arthritis. AB - The objectives of treatment in rheumatoid arthritis (RA) are to reduce temporary symptoms due to inflammatory activity and, more importantly, to preserve function. The introduction of potent disease-modifying anti-rheumatic drugs (DMARDs) in recent years has increased the opportunities for effective treatment. However, these treatments come at a substantially higher cost than traditional DMARDs and therefore compete with other essential interventions for limited resources. They have triggered a debate on whether they represent an efficient use of resources, which patients should be treated, when, and for how long. Cost effectiveness analysis attempts to estimate the trade-offs involved in these decisions and to provide information that can help in making them. However, in chronic progressive diseases, health gains and any potential associated economic benefits are often most evident in the long-term. As a consequence, the impact of new treatments has to be estimated using models that can project available knowledge, such as results from clinical trials or short-term follow-up studies in clinical practice, into the future. These models also allow scenarios to be explored that provide the best value for money, for example by defining subgroups for which treatment is most effective, or criteria that define when treatment should be stopped. Economic evaluation in RA has a long tradition, with the first study performed about 20 years ago. However, with the recent drug introductions, the field has witnessed an explosion of economic studies. Modelling techniques have become more sophisticated to overcome concerns about their validity. At the same time, they may appear less transparent, making it difficult for non specialists to understand the details. This article, rather than reviewing all published models and comparing them, attempts to illustrate the inputs required for such studies, and the influence that different approaches and datasets can have on the results. PMID- 17343249 TI - Indications, complications, and results of shoulder arthroplasty. AB - OBJECTIVE: To provide estimates of patient outcomes following shoulder arthroplasty using Neer-II type humeral prosthesis and to examine variation in outcomes due to patient and prosthesis characteristics. METHODS: North American and Western European published articles were identified through a computerized literature search and bibliography review. Studies were included if they enrolled 15 or more patients, discriminated between hemi-arthroplasty (HEMI) and total shoulder arthroplasty (TSA) and measured pain relief, gain in range of motion (ROM), radiographic follow-up (> 2 years), short- and long-term complications, and revision surgery. RESULTS: A total of 40 studies satisfied the inclusion criteria. The total number of patients enrolled was 3584. The mean follow-up was 59 months. The mean patient age was 62 years, 65% of patients were women and 73% underwent TSA. All reports showed relevant pain relief, increase in ROM, and high satisfaction rates for HEMI and TSA in both osteoarthritis (OA) and rheumatoid arthritis (RA). The overall rate of revision was 8%. Significant differences between HEMI and TSA for both diagnoses were found for all outcome parameters. CONCLUSION: Shoulder arthroplasty is a safe and effective procedure for OA and RA patients. The diagnosis, shoulder pathology, and prosthesis specifics were significant predictors of outcomes. We therefore emphasize that conclusions on the outcome of shoulder arthroplasty can only be made if differentiated between these patient and prosthesis specifics. Limitations in the reporting style of these articles severely constrain the ability to explore variation in outcomes due to study, patient, or prosthesis characteristics and restrict their generalisability. PMID- 17343250 TI - Tumour necrosis factor (TNF)alpha -308 G/G promoter polymorphism and TNFalpha levels correlate with a better response to adalimumab in patients with rheumatoid arthritis. AB - OBJECTIVE: To investigate the influence of -308 tumour necrosis factor-alpha (TNFalpha) promoter polymorphism and circulating TNFalpha levels in the clinical response to adalimumab treatment in patients with rheumatoid arthritis (RA). METHODS: Eighty-one patients with active RA were genotyped for the -308 TNFalpha polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and subdivided into two groups for each polymorphism (G/A and G/G genotype). All received 40 mg of adalimumab subcutaneously every other week. We compared the groups' clinical responses to adalimumab at 8, 16, and 24 weeks using the Disease Activity Score in 28 joints (DAS28). RESULTS: Both groups showed a significant improvement from baseline. A significant difference between groups was found at week 24. We found that 88.2% of G/G versus 68.4% of G/A for the -308 polymorphism were DAS28 responders (p = 0.05). The score improvement at week 24 was 2.5 +/- 1.3 in the G/G group and 1.8 +/- 1.3 in the G/A group for the -308 polymorphism (p = 0.04). The median of serum TNFalpha levels of the G/A group were lower than those of the G/G group, and statistically different at weeks 8 and 24 (p < 0.039 and p < 0.043). When comparing baseline levels to those achieved at 8, 16, and 24 weeks for the whole group, only responder patients showed a statistically significant overall increase in TNFalpha over time (p < 0.000001). CONCLUSION: A relationship between DAS28 improvement, the -308 G/G polymorphism, and increased circulating TNFalpha levels was found in Chilean RA patients treated with adalimumab. PMID- 17343251 TI - Lack of agreement between patients' and physicians' perspectives of rheumatoid arthritis disease activity changes. AB - OBJECTIVE: To obtain information on changes in patients' satisfaction (PATSAT) and physicians' global assessment (PhGASS) with regard to rheumatoid arthritis (RA) activity fluctuations. METHODS: Eighty-eight RA outpatients out of 207 investigated were assessed for 3 months on average after the initial evaluation. PATSAT (1 = excellent to 5 = unsatisfactory), PhGASS (visual analogue scale 1 100), and the 28-joint Disease Activity Score (DAS28) were assessed as at the first evaluation. The only prerequisite for enrolment was any therapeutic change at the first visit. Changes in PATSAT (SATCH) and PhGASS (PhGACH) were categorized and subsequently related to the DAS28 changes. Statistical evaluation was carried out by the Kruskal-Wallis test, the Mann-Whitney U-test, and by kappa statistics. RESULTS: To achieve a positive SATCH (n = 26/88 patients), a median DAS28 reduction of -1.06 (-25.0%) was necessary, whereas a considerably lower median increase of +0.16 (+10.5%) caused a negative SATCH. PhGASS (n = 38/88 patients) changed positively on a median DAS28 reduction of -0.82 (-16.0%), whereas it worsened at a mean DAS28 increase of +0.55 (+16.5%). Approximately 60% congruence between SATCH and PhGACH could be observed (kappa = 0.139). The DAS28 values preceding a positive SATCH and PhGACH were significantly higher (p < 0.001) than before a negative change. CONCLUSION: The patients' perspective with respect to improvement or worsening of RA is asymmetric. In contrast to the physicians' perspective, patients require greater improvement to be satisfied and less deterioration to be dissatisfied. These results may provide additional guidance in considerations about defining response and non-response in RA. PMID- 17343252 TI - Heat shock protein 70 membrane expression on fibroblast-like synovial cells derived from synovial tissue of patients with rheumatoid and juvenile idiopathic arthritis. AB - OBJECTIVE: To screen fibroblast-like synovial cells derived from synovial tissue of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) patients for the membrane expression of the heat shock protein Hsp70. METHODS: We performed flow cytometric (fluorescence-activated cell sorting, or FACS) analysis on fibroblast-like synovial cells of 15 RA patients and three JIA patients to investigate Hsp70 membrane expression. Skin fibroblasts derived from the operation wound (n = 4) and peripheral blood mononuclear cells (PBMC) of seven RA and three JIA patients were also tested. Peripheral blood lymphocytes (PBL) and skin fibroblasts of 10 healthy individuals were used as negative controls. RESULTS: A significantly higher percentage of Hsp70 membrane expression was found on fibroblast-like synovial cells derived from arthritis-affected joints in RA patients (mean 47.7%) when compared with autologous skin fibroblasts (mean 9.5%, p < 0.001) and control skin fibroblasts (mean 5.6%, p < 0.001) or autologous PBL (mean CD45/Hsp70-positive 10.4%, p < 0.001) and control PBL (mean CD45/Hsp70 positive 7.7%, p < 0.001). A high percentage of Hsp70 membrane expression was also observed on fibroblast-like synovial cells derived from three patients with JIA (mean 35.2%) when compared with autologous PBL (mean CD45/Hsp70-positive 10.4%). Synovial cells derived from non-affected joints in a patient with RA who underwent synovectomy for trauma showed low expression of Hsp70 (10.9%). CONCLUSION: Fibroblast-like synovial cells derived from patients with severe course of RA and JIA are strongly positive for membrane-expressed Hsp70. PMID- 17343253 TI - Ultrasonography and magnetic resonance imaging of heel fat pad inflammatory oedematous lesions in rheumatoid arthritis. AB - OBJECTIVE: To study heel fat pad (HFP) inflammatory-oedematous lesions in selected patients with rheumatoid arthritis (RA) using ultrasonography (US) and power Doppler US (PDUS), to describe and compare US features of these lesions with those obtained with magnetic resonance imaging (MRI), and to describe changes in the lesions after a short-term follow-up with conventional or anti tumour necrosis factor-alpha (TNFalpha) therapy. METHODS: Twelve heels of eight RA outpatients with HFP inflammatory-oedematous lesions were studied by US, PDUS, and unenhanced MRI. All the patients were followed up and US was performed after 3 months. Five patients started on anti-TNFalpha therapy. RESULTS: HFP lesions appeared at US as a heterogeneous and hypoechoic subcalcaneal mass, with loss of normal lobular structure and increased thickness of HFP, because of focal rupture of fibrous septae with oedema and fluid. PDUS showed peripheral vascularization of HFP lesions in 9/12 heels. In 3/12 heels some vascular signals was also detectable inside the lesion, always along the residual echoic septa. No detectable flow was observed within the central fluid-filled spaces. MRI of the HFP lesions showed areas of mean intensity in T1-weighted sequences and high intensity in T2-weighted sequences, with poorly or well-defined margins. After 3 months, PDUS showed reduction in HFP lesion vascularity (associated with reduction in pain) in 10/12 heels, while poor regression of grey-scale US abnormalities was observed. CONCLUSIONS: Both US and MRI are capable of demonstrating structural abnormalities in the HFP. PDUS is useful to assess and monitor inflammatory vascularization of the HFP lesions. PMID- 17343254 TI - Potential triggering infections of reactive arthritis. AB - OBJECTIVES: The aim of the study was to investigate possible triggering infections causing reactive arthritis (ReA) of urogenital origin. METHODS: One hundred and twenty ReA patients, 85 control group patients with other arthritides (61 with rheumatoid arthritis, 13 with osteoarthritis, and 11 with microcrystal arthritis), and 52 healthy persons were tested for urogenital tract inflammation and several infectious agents. Ligase chain reaction was used for detection of Chlamydia trachomatis (CT). Genital mycoplasmas Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) were tested using the Mycoplasma Duo Test (MDT). Only titres greater than 10(4) CCU/mL were accepted as pathogenecity threshold levels for Uu. RESULTS: Inflammation of the urogenital tract (most frequently urethritis in men and cervicitis in women) was found in 95% of patients with acute ReA. Possible causative pathogens were identified in 58% of ReA patients. CT was found in 29%, Uu in 21%, and Mh in 8% of patients with ReA. While CT and Uu were found more often in HLA-B27-positive than in HLA-B27-negative patients, this was statistically proved only for CT. In ReA males Uu was found four times more frequently than in men with other arthritides. CONCLUSIONS: In active ReA of urogenital origin, inflammation of the urogenital tract is found in the majority of patients. Although CT is the main microorganism associated with urethritis in men and cervicitis in women, mycoplasmas, especially Uu, may be possible aetiological factors for ReA. PMID- 17343255 TI - Comparison of the different classification criteria sets for primary Sjogren's syndrome. AB - OBJECTIVE: To assess the comparability of different classification criteria sets for primary Sjogren's syndrome (pSS). METHODS: In a prospective study we examined all patients with suspected pSS who were admitted to our Department of Rheumatology or referred to our outpatient clinic between 1 January 2001 and 31 December 2002. The Copenhagen, Californian, 1996 European, and American-European consensus group (US-EU) criteria sets were used to assess each patient. RESULTS: Ninety out of 222 patients (41%) were diagnosed with pSS by fulfilling at least one classification criteria set. The highest number of patients who were diagnosed with pSS fulfilled the European criteria set (36%), followed by the Copenhagen (28%), the US-EU (26%), and the Californian (9%) criteria sets. On average, the group of patients fulfilling the Californian criteria set were 5.6 years older than the patients in the other three groups (p < 0.05). In addition, the disease duration before diagnosis was 2.6 years longer than in the other three groups. The groups of patients fulfilling either the Californian or the US EU criteria sets had a higher prevalence of leucopaenia (p < 0.05). Those fulfilling the US-EU criteria set also had a higher prevalence of arthritis (p < 0.05). No significant differences were found in the prevalence of the other clinical and laboratory parameters studied. CONCLUSIONS: Different patients are diagnosed with pSS if different classification criteria sets are used. Therefore, studies based on different classification criteria sets for diagnosing pSS are not directly comparable. PMID- 17343256 TI - Hormone replacement therapy may prevent the development of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. AB - BACKGROUND: Isolated pulmonary hypertension (iPHT) is a near-fatal consequence of systemic sclerosis (SSc); in female patients, the risk of its development is increased during the post-menopausal period, when the protective effects of oestrogens on the endothelium decrease. In many animal and human models, hormone replacement therapy (HRT) and oestrogen administration proved efficacious in counteracting many mechanisms that might be implicated in the pathogenesis of iPHT. Accordingly, it has been hypothesized that HRT might help to prevent the development of iPHT. METHODS: A retrospective cohort study was conducted on 61 SSc patients with the limited cutaneous form of the disease and no sign of pulmonary hypertension on echocardiogram (pulmonary artery pressure, PAP > 35 mmHg) at the time of menopause. All the patients had to be stably treated with calcium-channel blockers and not to have risk factors for secondary PHT throughout the duration of the observational period. RESULTS: Twenty patients (32.8%) received HRT for a mean of 6.7 +/- 3.7 years. None of these patients developed iPHT after a mean of 7.2 +/- 3.5 years from menopause, whereas eight out of 41 patients not receiving HRT (19.5%) developed iPHT after a similar time period (7.5 +/- 3.9 years, p = 0.032). These rates were not explained by differences between the two groups with respect to autoantibodies, age, age at onset of SSc, diffusing capacity of the lung for carbon monoxide (DLCO) at menopause, or duration of therapy with calcium-channel blockers. CONCLUSION: HRT administration may be effective in SSc post-menopausal women, preventing the development of iPHT. PMID- 17343257 TI - Expression of cytokines, chemokines, and chemokine receptors in oral ulcers of patients with Behcet's disease (BD) and recurrent aphthous stomatitis is Th1 associated, although Th2-association is also observed in patients with BD. AB - OBJECTIVE: Although the pathogenesis of Behcet's disease (BD) is unknown, immune dysfunction appears to be involved. To improve understanding of the role of T cells and cytokines in BD, the current study analysed the localization and extent of expression of T cell subsets, cytokines, chemokines, and chemokine receptors in oral ulcers from BD patients and for comparison in oral ulcers from patients with recurrent aphthous stomatitis (RAS), as well as in healthy oral mucosa. METHODS: Biopsies from oral ulcers of 25 BD patients and 19 RAS patients and oral mucosa from six healthy volunteers were immunoperoxidase stained. RESULTS: Both CD4- and CD8-positive T cells were present in the oral ulcers of BD and RAS patients. The T helper (Th)1 cytokines interleukin (IL)-12, interferon (IFN) gamma, and tumour necrosis factor (TNF)alpha and the Th1-associated chemokine receptors CCR5 and CXCR3 were increased in both patient groups as compared to normal controls, indicating the involvement of a Th1 immune response in the immunopathology of both BD and RAS. However, the Th2 cytokine IL-4 was only observed in oral ulcers of BD patients but not in RAS patients. CONCLUSION: This is the first study that shows the presence of pro-inflammatory cytokines, as well as Th1-associated chemokine receptors, in the oral ulcers of BD patients, as well as RAS patients, at a protein level. However, the expression of the Th2 cytokine IL-4 within the oral lesions of only BD patients is suggestive of a more complex antigenic stimuli in BD patients compared with RAS patients. PMID- 17343258 TI - Clinical study on the effect of infrared radiation of a tiled stove on patients with hand osteoarthritis. AB - OBJECTIVE: To explore the effect of infrared radiation of a tiled stove on patients with hand osteoarthritis (OA). METHODS: A randomized controlled crossover study was performed with 45 patients with hand OA. This sample was randomly assigned to two groups: group A [first 3 hours spent three times a week during 3 weeks in a heated tiled stove room ('Stove Period') and after 2 weeks without treatment this group was observed for another 3 weeks ('Control Period')]; and group B (first assigned to the control period and the stove period following the treatment-free period). Assessments included the visual analogue scale (VAS) for general pain, pain in the hands, and global hand function, grip strength, the Moberg Picking-up Test (MPUT), the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), and the Medical Outcomes Study (MOS) 36-item Short-Form Health Status Survey (SF-36). RESULTS: Fourteen (31%) patients improved on the VAS for general pain at the end of the tiled stove period as compared to 10 patients (22%) during the control period (p = 0.314, chi2-test). The AUSCAN pain domain showed a significant improvement after the tiled stove period (p = 0.034). Others pain parameters analysed (VAS for pain in hands and SF 36 bodily pain) showed moderate but not significant improvement (p = 0.682 and p = 0.237, respectively) compared to the control period. CONCLUSION: This study did not prove positive effects of the tiled stove exposure, although the numerical improvement in all pain measures suggests some possible positive effects on this symptom of hand OA. PMID- 17343259 TI - Spontaneous retroperitoneal bleeding from renal microaneurysms and pancreatic pseudocyst in a patient with systemic lupus erythematosus. AB - Visceral vasculitis and pancreatic pseudocyst are rare manifestations of systemic lupus erythematosus (SLE). We describe a patient with SLE who presented with spontaneous bilateral perinephric and retroperitoneal haematoma secondary to polyarteritis nodosa (PAN)-like vasculitis of the renal arteries, which subsequently evolved into systemic vasculitis with pancreatic pseudocyst formation. PMID- 17343260 TI - Decrease of proteinuria in a patient with adult-onset Still's disease and glomerulonephritis after anti-TNFalpha therapy. AB - We report the case of a 41-year-old man diagnosed with Still's disease. Multiple disease-modifying anti-rheumatic drug (DMARD) therapies failed to induce disease remission or to prevent progressive joint destruction. The man presented with active arthritis and classical Still's rash accompanied by fever. Anti-tumour necrosis factor-alpha (TNFalpha) therapy was planned but during the medical check up prior to the biological therapy, renal insufficiency with marked proteinuria (PU) was discovered. With PU of 912 mg/24 h a renal biopsy was performed and a histopathological evaluation revealed the diagnosis of a residual mesangio proliferative immunocomplex-based glomerulonephritis (GN). After excluding contraindications, infliximab therapy was initiated and a good response of the arthritis was documented after 6 weeks. A significant decrease in PU (279 mg/24 h) was noted after the third infliximab infusion. Because of an allergic reaction during the fifth dose, the infliximab was discontinued. During the time frame without anti-TNFalpha therapy, active joint disease reoccurred and the proteinuria increased significantly. Because of the active disease entanercept therapy was initiated. The arthritis diminished and the PU was reduced markedly within 4 weeks. In the follow-up period of 12 months a good response to therapy was sustained. As described by other investigators, the joint disease showed a rapid and sustained response to anti-TNFalpha therapy. The decrease in proteinuria during biological therapy was notable. It was concluded that the significant decrease in PU in this patient was achieved by eliminating the inflammatory activity of the underlying kidney disease. PMID- 17343261 TI - Plasma IL-6, plasma VEGF, and serum YKL-40: relationship with disease activity and radiographic progression in rheumatoid arthritis patients treated with infliximab and methotrexate. PMID- 17343262 TI - Severe mesenteric and coronary vasculitis: a late and uncommon complication in a patient with chronic discoid lupus erythematosus. PMID- 17343263 TI - Hypoparathyroidism: a rare cause of spondyloarthropathy. PMID- 17343265 TI - Conduct disorder, war zone stress, and war-related posttraumatic stress disorder symptoms in American Indian Vietnam veterans. AB - This study examined whether conduct disorder (CD) was associated with war zone stress and war-related post-traumatic stress disorder (PTSD) symptoms in American Indian (AI) Vietnam veterans. Cross-sectional lay-interview data was analyzed for 591 male participants from the American Indian Vietnam Veterans Project. Logistic regression evaluated the association of CD with odds of high war zone stress and linear regression evaluated the association of CD and PTSD symptom severity. Childhood CD was not associated with increased odds of high war zone stress. Conduct disorder was associated with elevated war-related PTSD symptoms among male AI Vietnam Veterans independent of war zone stress level and other mediators. Future efforts should examine reasons for this association and if the association exists in other AI populations. PMID- 17343266 TI - The increasing internationalization of mainstream posttraumatic stress disorder research: a bibliometric study. AB - The aim of this study was to quantify changes in the national contributions to research related to posttraumatic stress disorder (PTSD) from 1983 through 2002. Using the Web of Science database (Thomson Scientific, Philadelphia, PA), we classified articles according to the year of publication and the country of the authors. The number of publishing countries increased from 7 between 1983 and 1987 to 39 between 1998 and 2002. Meanwhile, the U.S. output share declined from 87.6% in the first period to 62.4%. Although the number of countries publishing on PTSD has steadily increased, research is still dominated qualitatively and quantitatively by developed countries. These findings suggest a growing international acceptance of this diagnostic category. However, the immaturity of PTSD research is demonstrated by the concentration of publications in a few countries. PMID- 17343267 TI - Apparently novel genetic syndrome of pachygyria, mental retardation, seizure, and arachnoid cysts. AB - We report on an apparently new syndrome in a consanguineous family with seven members, three of whom have cerebral anomalies including pachygyria and arachnoid cysts along with mental retardation and seizures. The two patients with seizure disorders also had multiple enlarged perivascular spaces seen in the white matter of the centrum semiovale. Our data provide a contribution to the accumulating knowledge on familial cerebral anomalies including arachnoid cysts and lissencephaly. Given the lack of mutation in known lissencephaly genes such as LIS1, 14-3-3epsilon, and DCX, this syndrome may constitute a new phenotype with autosomal recessive inheritance. PMID- 17343268 TI - Exclusion of OGDH and BMP4 as candidate genes in two siblings with autosomal recessive DOOR syndrome. PMID- 17343269 TI - Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations. AB - Craniosynostosis, the premature fusion of one or more cranial sutures, affects 1 in 2,500 live births. Isolated single-suture fusion is most prevalent, with sagittal synostosis occurring in 1/5,000 live births. The etiology of isolated (nonsyndromic) single-suture craniosynostosis is largely unknown. In syndromic craniosynostosis, there is a highly nonrandom pattern of causative autosomal dominant mutations involving TWIST1 and fibroblast growth factor receptors (FGFRs). Prior to our study, there were no published TWIST1 mutations in the anti osteogenic C-terminus, recently coined the TWIST Box, which binds and inhibits RUNX2 transactivation. RUNX2 is the principal master switch for osteogenesis. We performed mutational analysis on 164 infants with isolated, single-suture craniosynostosis for mutations in TWIST1, the IgIIIa exon of FGFR1, the IgIIIa and IgIIIc exons of FGFR2, and the Pro250Arg site of FGFR3. We identified two patients with novel TWIST Box mutations: one with isolated sagittal synostosis and one with isolated coronal synostosis. Kress et al. [2006] reported a TWIST Box "nondisease-causing polymorphism" in a patient with isolated sagittal synostosis. However, compelling evidence suggests that their and our sequence alterations are pathogenic: (1) a mouse with a mutation of the same residue as our sagittal synostosis patient developed sagittal synostosis, (2) mutation of the same residue precluded TWIST1 interaction with RUNX2, (3) each mutation involved nonconservative amino acid substitutions in highly conserved residues across species, and (4) control chromosomes lacked TWIST Box sequence alterations. We suggest that genetic testing of patients with isolated sagittal or coronal synostosis should include TWIST1 mutational analysis. PMID- 17343270 TI - Clinical and molecular cytogenetic characterization of two patients with non mutational aberrations of the FMR2 gene. AB - We report on two patients; a female having mild mental retardation (MR) with a balanced translocation, 46,XX,t(X;15)(q28;p11.2), and a male diagnosed as having mucopolysaccharidosis type II (MPS II or Hunter syndrome) with atypical early onset MR and a normal male karyotype. Molecular cytogenetic analyses, including fluorescence in situ hybridization and array-based comparative genomic hybridization using an in-house X-tiling array, revealed that first patient to have a breakpoint at Xq28 lying within the FMR2 gene and the second to have a small deletion at Xq28 including part of FMR2 together with the IDS gene responsible for MPS II. In Patient 1, X-chromosome inactivation predominantly occurred in the normal X in her lymphocytes, suggesting that her MR might be explained by a disruption of the FMR2 gene on der(X) t(X;15) concomitant with the predominant inactivation of the intact FMR2 gene in another allele. We compared phenotypes of Patient 2 with those of MPS II cases with deletion of the IDS gene alone reported previously, suggesting that the early-onset MR might be affected by the additional deletion of FMR2. PMID- 17343271 TI - Depressive and anxiety symptoms in Sydenham's chorea. PMID- 17343272 TI - Parkinson's disease data and organizing center. PMID- 17343273 TI - PRKCG mutation (SCA-14) causing a Ramsay Hunt phenotype. AB - Progressive myoclonic ataxia, also referred to as Ramsay Hunt syndrome, is characterized by a combination of myoclonus and cerebellar ataxia, infrequently accompanied by tonic-clonic seizures. Its differential diagnosis overlaps with progressive myoclonic epilepsy, a syndrome with myoclonus, tonic-clonic seizures, progressive ataxia and dementia. In patients with progressive myoclonic epilepsy, specific diseases can frequently be recognized, but the diagnostic yield in progressive myoclonic ataxia is much lower. We describe a patient who presented with multifocal myoclonus in his thirties and who later developed cerebellar ataxia and focal dystonia. His father was similarly affected. Genetic studies revealed a mutation in the protein kinase C gamma (PRKCG) gene, known to cause spinocerebellar ataxia type 14 (SCA-14). This case illustrates that both myoclonus and dystonia are part of the clinical spectrum in SCA-14 and that myoclonus can even be the presenting symptom. We suggest that SCA-14 should be considered in the differential diagnosis of progressive myoclonic ataxia. PMID- 17343274 TI - Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor. AB - The purpose of this study was to evaluate interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) in essential tremor (ET). Proper treatment of ET is contingent upon correct assessment of the severity, loss of function, and disability related to tremor. Videotape recordings of 17 subjects with ET evaluated with the TRS were produced and sent to 59 raters. Once the raters returned the videotape and completed the score sheet, they were mailed a second tape with the same recordings presented in a different order. In the interrater reliability evaluation, modified Kappa statistics for seven tremor type composites ranged from 0.10 to 0.65 in the first videotape and 0.17 to 0.62 in the second videotape. Interrater reliabilities were greater for Part A items (magnitude of tremor in different body parts) than for Part B items (tremor in writing and drawings) of the TRS. The average Spearman correlation was 0.87, indicating very good consistency between the two videotapes, but correlations for Part A were somewhat better than for Part B. It is best when the same rater performs repeated measures of tremor on a patient, particularly when judging tremor in handwriting and drawings. Training of raters on use of the TRS would help standardize judgement. PMID- 17343275 TI - Effect of medical and surgical interventions on health-related quality of life in Parkinson's disease. AB - Motor-related parameters are the standard outcome parameters for treatment interventions. Nonetheless, subjective appraisals about the consequences of treatment on health-related quality of life (HRQoL) are meanwhile established and may uncover important aspects of interventions. We have reviewed the literature with a defined search strategy and collected 61 clinical trials, which have used HRQoL as a planned outcome parameter. The articles were rated similarly as for the Task Force report of the Movement Disorder Society on interventions for Parkinson's disease (PD), but the relevant outcome parameter was HRQoL. We found that unilateral pallidotomy, deep brain stimulation of the subthalamic nucleus, and rasagiline are efficacious to improve the HRQoL of PD patients. For many other interventions, the efficacy to improve HRQoL in the PD setting cannot be considered to be proven so far. HRQoL should be part of future trial designs and more research is necessary to understand the determinants of QoL in PD. PMID- 17343276 TI - On the selection of patients with developmental delay/mental retardation and autism spectrum disorders for genetic studies. PMID- 17343277 TI - Case completeness and data accuracy in the Centers for Disease Control and Prevention's National Program of Cancer Registries. AB - BACKGROUND: Issues of case completeness (CC) and data quality within the National Program of Cancer Registries (NPCR)-Cancer Surveillance System (NPCR-CSS) are assessed in part by the NPCR Technical Assistance and Audit Program (NPCR-TAA). In addition, the NPCR Annual Program Evaluation Instrument (NPCR-APEI) provides information about NPCR-supported central cancer registries (CCRs). The current report includes a unique, national-level analysis of NPCR-TAA results linked with NPCR-APEI data and other covariates. METHODS: NPCR-TAA results for 34 CCRs were aggregated across diagnosis years 1998 to 2001 for analysis of average CC rates and site-specific data accuracy (DA) rates by covariates obtained from the NPCR APEI, United States Cancer Statistics (USCS) publications, and the North American Association of Central Cancer Registries (NAACCR) Web site. Site-specific DA rates were calculated for the 13 data elements examined in the audit program. Small-sample Student t tests were used to determine statistically significant differences in covariates (alpha = .05). RESULTS: Overall, the average CC and DA rates were 96.4% and 95%, respectively. Both site- and data element-specific DA issues were highlighted. Higher CC and DA rates were observed for CCRs that were staffed with more certified tumor registrars, had supplementary sources reporting, and met USCS publication standards and/or achieved NAACCR certification. CONCLUSIONS: Study findings underscored the importance of CCRs having adequate, well-trained staff, procuring supplemental reporting sources, and attaining compliance with national data standards. The study results also demonstrated the overall high completeness and quality of NPCR-CSS data and provided guidance to users of the data. PMID- 17343278 TI - Effect of dermatan sulfate glycosaminoglycans on the quasi-static material properties of the human medial collateral ligament. AB - The glycosaminoglycan of decorin, dermatan sulfate (DS), has been suggested to contribute to the mechanical properties of soft connective tissues such as ligaments and tendons. This study investigated the mechanical function of DS in human medial collateral ligaments (MCL) using nondestructive shear and tensile material tests performed before and after targeted removal of DS with chondroitinase B (ChB). The quasi-static elastic material properties of human MCL were unchanged after DS removal. At peak deformation, tensile and shear stresses in ChB treated tissue were within 0.5% (p>0.70) and 2.0% (p>0.30) of pre treatment values, respectively. From pre- to post-ChB treatment under tensile loading, the tensile tangent modulus went from 242+/-64 to 233+/-57 MPa (p=0.44), and tissue strain at peak deformation went from 4.3+/-0.3% to 4.4+/-0.3% (p=0.54). Tissue hysteresis was unaffected by DS removal for both tensile and shear loading. Biochemical analysis confirmed that 90% of DS was removed by ChB treatment when compared to control samples, and transmission electron microscopy (TEM) imaging further verified the degradation of DS by showing an 88% reduction (p<.001) of sulfated glycosaminoglycans in ChB treated tissue. These results demonstrate that DS in mature knee MCL tissue does not resist tensile or shear deformation under quasi-static loading conditions, challenging the theory that decorin proteoglycans contribute to the elastic material behavior of ligament. PMID- 17343279 TI - Sagittal pelvic mal-rotation and positioning of the acetabular component in total hip arthroplasty: Three-dimensional computer model analysis. AB - Mal-rotation of pelvis on the sagittal plane, which is common in patients with fixed spinal kyhposis, for example, ankylosing spondylitis, can cause error in cup positioning when hip arthroplasty is performed. The present study was performed to quantify the effects of sagittal pelvic mal-rotation on the final cup position and to evaluate different methods of cup positioning to compensate for the mal-rotation. Three-dimensional reconstruction of computer tomograms of 15 sets of full pelvi was performed. Two methods of cup insertion were simulated and compared: a method mimicking genuine surgery (anatomical positioning) and one that compensates for the sagittal pelvic mal-rotation (functional positioning). Sagittal pelvic mal-rotation of more than 20 degrees , if ignored, resulted in a cup with an anterversion of more than 30 degrees and an inclination of more than 55 degrees. Half of the cup surface was not in contact with host bone when the cup position was maintained at 20 degrees anteversion and 45 degrees inclination in a patient with 50 degrees sagittal pelvic mal-rotation. The usual method of cup positioning may need to be modified in patients with sagittal pelvic mal rotation in order to maintain the desired cup position. For each 10 degrees of sagittal pelvic mal-rotation beyond 20 degrees of mal-rotation, the cup needs to be put in such that it is 5 degrees less inclined and anteverted. PMID- 17343280 TI - Estimation of the mechanical property of meniscus using ultrasound: examinations of native meniscus and effects of enzymatic digestion. AB - We previously developed a novel ultrasound assessment system featuring wavelet transform to evaluate the material properties of articular cartilage. We aimed in this study to demonstrate the feasibility of quantitative evaluation of meniscus using ultrasound and to elucidate the relationships between its acoustic, mechanical, and biochemical properties. Meniscal disc specimens from mature pigs were assessed by ultrasound and compression testing, and their correlation was analyzed. A positive correlation was found between the ultrasound signal intensity and apparent Young's modulus (r=0.61). Subsequently, the porcine meniscal discs were treated with various enzymes and then characterized by ultrasound, by compression tests, by biochemical analyses, and by histology and immunohistochemistry. The signal intensity was decreased not by hyaluronidase but by collagenase treatment. Hyaluronidase-treated menisci showed a discrepancy between acoustic and mechanical properties, suggesting that the ultrasound reflection could not detect a reduction in proteoglycan content. Also, ultrasound signal intensity could only reflect superficial layers of the material. Several limitations exist at present, and further studies and improvements of the device are required. However, given the noninvasive nature and the requirement of only small equipment, this ultrasound assessment system will be an instrumental diagnostic tool for meniscal function in both research and clinical fields. PMID- 17343281 TI - Cartilaginous deposits in subchondral bone in regions of exposed bone in osteoarthritis of the human knee: histomorphometric study of PRG4 distribution in osteoarthritic cartilage. AB - The objective of this study was to identify and characterize cartilaginous deposits aggregates in the subchondral bone in areas of the human osteoarthritic knee with exposed bone. A specific aim was to determine the distribution of the joint lubrication molecule, lubricin/superficial zone protein [referred to by its gene, proteoglycan4 (PRG4)], in these cartilaginous deposits and in osteoarthritic cartilage. This work was carried out in the context of assessing the potential contribution of these chondrocyte aggregates for joint resurfacing in certain cartilage repair procedures. The discarded bone cuts of femoral condyles and tibial plateaus were collected from 11 patients with advanced osteoarthritis (OA) of the knee during total knee arthroplasty; 9 women and 2 men with a mean age of 68 years. Sections of paraffin-embedded tissue were stained with Safranin-O, and with antibodies to type II collagen, alpha-smooth muscle actin (SMA), and PRG4. Chondrocyte aggregates were found in the subchondral bone of regions of exposed bone in sections from five individuals. The average diameter of cartilaginous aggregates was 152 microm, and the average depth of the aggregates below the surface was about 475 microm. Most aggregates were fibrocartilaginous and stained positive for type II collagen. Of interest was the finding that the cartilaginous deposits and osteoarthritic cartilage contained PRG4. Only a small percentage of chondrocytes stained positive for SMA. Cartilaginous deposits containing chondrocyte aggregates exist in subchondral bone in regions of exposed bone in some patients with advanced OA of the knee. These cells may be able to contribute to the resurfacing of the joint in certain cartilage repair procedures. PMID- 17343282 TI - Predicting revision risk for aseptic loosening of femoral components in total hip arthroplasty in individual patients--a finite element study. AB - Advances in surgical procedure, prosthesis design, and biomaterials performance have considerably increased the longevity of total joint replacements. Preoperative planning is another step in joint replacement that may have the potential to improve clinical outcome for the individual patient, but has remained relatively consistent for a long time. One means of advancing this aspect of joint replacement surgery may be to include predictive computer simulation into the planning process. In this article, the potential of patient specific finite element analysis in preoperative assessment is investigated. Seventeen patient-specific finite element models of cemented Charnley reconstructions were created, of which six were early (<10 years) revisions. Creep was simulated using a Maxwell model, and fatigue damage was simulated using an anisotropic continuum damage formulation. Account was taken of the relationship between annual loading cycles and age, and stair-climbing loads were included using a walking to stair-climbing cycle ratio of 9:1. Simulations for the equivalent of 10 years of loading were performed. Accumulated damage, inducible displacement, and migration were computed. Five of the six early revisions had the highest migration indicating that migration could have been used to identify early failures of these prostheses. Resultant migration showed the most significant difference between the early revised and unrevised groups (p = 0.0024). Furthermore, this trend was apparent from 1 year postimplantation (p = 0.0052). This ability to differentiate early revisions shows that computational simulation of aseptic loosening in cemented prostheses could prove clinically useful in helping surgeons optimize the preoperative plan for individual patients. PMID- 17343283 TI - Targeting of cell survival genes using small interfering RNAs (siRNAs) enhances radiosensitivity of Grade II chondrosarcoma cells. AB - The main treatment for chondrosarcoma is surgical resection with a wide margin. However, there are certain chondrosarcomas, such as those found in the pelvis and the spine, which cannot be resected adequately with surgery alone. Unfortunately, most chondrosarcomas are resistant to radiation and chemotherapy. Radiation and chemotherapy are thought to kill chondrosarcoma cells by inducing apoptosis, or programmed cell death. In this article, we hypothesize that antiapoptotic gene silencing enhances radiosensitivity in chondrosarcoma cells by facilitating apoptotic pathways. We knocked down antiapoptotic genes in chondrosarcoma cells using small interfering RNAs (siRNAs). Two well-established Grade II human chondrosarcoma cell lines were pretreated with siRNAs that specifically target mRNAs for Bcl-2, Bcl-xL, or XIAP. The cells were then treated with radiation. Cell death was assessed by flow cytometry. Cell survival and proliferation were measured by clonogenic survival assays. Chondrosarcoma cells exhibited radioresistance and increased the expression of Bcl-2, Bcl-xL, and XIAP in response to radiation. When one of the Bcl-2, Bcl-xL, or XIAP genes was silenced with the corresponding siRNA, radiosensitivity increased up to 9.2-fold (p < 0.05). When two out of the three antiapoptotic mRNAs were knocked down simultaneously, there was an 11.3-fold increase in cell death after radiation (p < 0.05). Our findings support a novel therapeutic concept that gene silencing may be used as a molecular adjuvant therapy for radioresistant sarcomas. PMID- 17343284 TI - Role of neuropeptides in inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is a chronic, relapsing condition involving complex interactions between genes and the environment. The mechanisms triggering the initial attack and relapses, however, are not well understood. In the past several years the enteric nervous system (ENS) has been implicated in the pathophysiology of IBD. Both the ENS and the central nervous system (CNS) can amplify or modulate aspects of intestinal inflammation through secretion of neuropeptides that serve as a link between the ENS and CNS. Neuropeptides are defined as any peptide released from the nervous system that serves as an intercellular signaling molecule. Neuropeptides thought to play a potentially key role in IBD include substance P, corticotropin-releasing hormone, neurotensin, vasoactive intestinal peptide, mu-opioid receptor agonists, and galanin. This review focuses on the role of these neuropeptides in the pathophysiology of IBD and discusses the cell types and mechanisms involved in this process. The available evidence that neuropeptide blockade may be considered a therapeutic approach in both Crohn's disease and ulcerative colitis will also be discussed. PMID- 17343285 TI - Correlation between the knee adduction torque and medial contact force for a variety of gait patterns. AB - The external knee adduction torque has been proposed as a surrogate measure for medial compartment load during gait. However, a direct link between these two quantities has not been demonstrated using in vivo measurement of medial compartment load. This study uses in vivo data collected from a single subject with an instrumented knee implant to evaluate this link. The subject performed five different overground gait motions (normal, fast, slow, wide, and toe-out) with simultaneous collection of instrumented implant, video motion, and ground reaction data. For each trial, the knee adduction torque was measured externally while the total axial force applied to the tibial insert was measured internally. Based on data collected from the same subject performing treadmill gait under fluoroscopic motion analysis, a regression equation was developed to calculate medial contact force from the implant load cell measurements. Correlation analyses were performed for the stance phase and entire gait cycle to quantify the relationship between the knee adduction torque and both the medial contact force and the medial to total contact force ratio. When the entire gait cycle was analyzed, R(2) for medial contact force was 0.77 when all gait trials were analyzed together and between 0.69 and 0.93 when each gait trial was analyzed separately (p < 0.001 in all cases). For medial to total force ratio, R(2) was 0.69 for all trials together and between 0.54 and 0.90 for each trial separately (p < 0.001 in all cases). When only the stance phase was analyzed, R(2) values were slightly lower. These results support the hypothesis that the knee adduction torque is highly correlated with medial compartment contact force and medial to total force ratio during gait. PMID- 17343286 TI - Anteroposterior pelvic radiographs to assess acetabular retroversion: high validity of the "cross-over-sign". AB - Acetabular retroversion has been proposed to contribute to the development of osteoarthritis of the hip. For the diagnosis of this condition, conventional AP pelvic radiographs may represent a reliable, easily available diagnostic modality as they can be obtained with a reproducible technique allowing the anterior and posterior acetabular rims to be visible for assessment. This study was designed to: (i) determine cranial, central, and caudal anatomic acetabular version (AV) from cadaveric specimens; (ii) establish the validity and reliability of the radiographic measurements of central acetabular anteversion; and (iii) determine the validity and reliability of the radiographic "cross-over-sign" to detect acetabular retroversion. Using 43 desiccated pelvises (86 acetabuli) the anatomic AVs were measured at three different transverse planes (cranially, centrally, and caudally). From these pelvises, standardized AP pelvic radiographs were obtained. To directly measure central AV, a modified radiographic method is introduced for the use of AP pelvic radiographs. The validity and reliability of this radiographic method and of the radiographic cross-over-sign to detect cranial acetabular retroversion were determined. The mean central and caudal anatomic AVs were approximately 20 degrees , and the mean cranial AV was 8 degrees . Cranial retroversion (AV < 0 degrees ) was present in 19 of 86 hips (22%). A linear correlation was found between the central and cranial AV. Below 10 degrees of central AV, all acetabuli were cranially retroverted. Between 10 degrees and 20 degrees , 30% of the acetabuli were cranially retroverted, and above 20 degrees , only 1 of 45 acetabuli was cranially retroverted. The radiographic measurement of the central AV (20.3 +/- 6.5 degrees ) correlated strongly with the anatomic AV (20.1 +/- 6.4 degrees ). The sensitivity of the cross-over-sign to detect a cranial acetabular anteversion of less than 4 degrees was 96%, its specificity 95%, and the positive predictive and negative predictive values 90% and 98%, respectively. Both the modified radiographic anteversion measurements and the cross-over-sign demonstrated substantial inter- and intraobserver reliability. Retroversion is almost exclusively a problem of the cranial acetabulum. The cranial AV is on average 12 degrees lower than the central AV, with the latter directly measurable from AP pelvic radiographs. A central AV of less than 10 degrees was associated with cranial retroversion. The presence of a positive cross-over-sign is a highly reliable indicator of cranial AV of <4 degrees. PMID- 17343287 TI - Interplay between kinetically slow thermal spin-crossover and metastable high spin state relaxation in an iron(II) complex with similar T1/2 and T(LIESST). AB - This paper describes the first material to show the well-known light-induced excited spin-state trapping (LIESST) effect, the metastable excited state of which relaxes at a temperature approaching its thermal spin-crossover. Cooling polycrystalline [FeL(2)][BF(4)](2).x H(2)O (L=2,6-bis[3-methylpyrazol-1 yl]pyridine; x=0-1/3) at 1 K min(-1) leads to a cooperative spin transition, taking place in two steps centered at 147 and 105 K, that is only 54 % complete by magnetic susceptibility. Annealing the sample at 100 K for 2 h results in a slow decrease in chi(M)T to zero, showing that the remainder of the spin crossover can proceed, but is kinetically slow. The crystalline high- and fully low-spin phases of [FeL(2)][BF(4)](2).x H(2)O are isostructural (C2/c, Z=8), but the spin-crossover proceeds via a mixed-spin intermediate phase that has a triple unit cell (C2/c, Z=24). The water content of the crystals is slowly lost on exposure to air without causing decomposition. However, the high-spin/mixed-spin transition in the crystal proceeds at 110+/-20 K when x=1/3 and 155+/-5 K when x=0, which correspond to the two spin-crossover steps seen in the bulk material. The high-spin state of the compound is generated quantitatively by irradiation of the low-spin or the mixed-spin phase at 10 K, and in approximately 70 % yield by rapidly quenching the sample to 10 K. This metastable high-spin state relaxes back to the low-spin ground state at 87+/-1 K in one, not two, steps, and without passing through the intermediate phase. This implies that thermal spin-crossover and thermally activated high-spin-low-spin relaxation in this material become decoupled, thus avoiding the physical impossibility of T(LIESST) being greater than T(1/2). PMID- 17343288 TI - Diphenic acid as a general conformational lock in the design of bihelical structures. AB - The bihelical (figure of "infinity") topology was examined from vantages of design, crystal structures, chirality, circular dichroism (CD) studies and molecular-orbital calculations. The minimalistic design envisaged the sequential linking of cystine to the anchor diphenic acid, which proved to be a general conformational lock. The bihelical compound 4 was obtained in two steps from diphenic anhydride 1 and cystine di-OMe. The chirality of 4 arises largely from the L-cystine. The bihelical compound 5 obtained from D-cystine di-OMe was found, by X-ray crystallography, CD studies, and optical rotation, to be the perfect mirror image of 4 prepared from L-cystine. The crystal structure of prototype 8, prepared by protocols used for 4 from the achiral cystine analogue cystamine, had a "U"-shaped conformation held together by intramolecular hydrogen bonds. Analysis of 4 and 5 show that the pairs of nine-membered beta-turn-like constructs made compact through hydrogen bonding with DMSO hold the key for the bihelical conformation. Another factor is the need for the presence of a ligand at the Calpha position. The absence of this, as in 8, allows major flexibility in the torsional angles around this critical region, promoting flexible alternatives. The CD analysis of 4, confirmed to be bihelical by X-ray crystallography, showed a typical negative band at about 210 A attributed to the beta-turn-like motif, and in the positive-band region a peak at about 227 A, generally related to the twist of the biphenyl unit. The cystamine analogue 8, which showed a "U"-type structure, presented a CD spectrum with no typical features. The total energy, derived from theoretical calculations by using the X ray structure data, support the bihelical structure for 4 and a "U"-shaped one for 8. The limited utility of such calculations was tested with composite 9. Composite 9, in which the anchor diphenic acid is linked to cystamine on the one hand and to cystine on the other, showed a CD spectrum similar to that of 4, and this coupled with molecular-orbital calculations, using data from 4 and 8, predict a bihelical structure for this compound. PMID- 17343289 TI - Molecule-responsive block copolymer micelles. AB - Ring-opening metathesis polymerization was used to generate an ABC triblock copolymer, containing complementary diamidopyridine (DAP) and thymine (THY) outer blocks, which assembles into spherical aggregates held together by DAP-THY noncovalent interactions. Addition of THY-containing small guest molecules results in complete opening and deaggregation of the block copolymer micelle. This molecular recognition and macroscopic response shows high selectivity to the guest structure, and tolerates only a small amount of conformational mobility in the THY guest. On the other hand, addition of a small DAP-containing guest does not break the aggregates, but instead, results in new micelles which show a different selectivity profile from the parent morphology. We have examined the effect of a number of structural features in the block copolymers, on both the extent and selectivity of their macroscopic response to guests (that is, opening of the micelle). This study has resulted in a set of structural guidelines, which help in the design of effective molecule-responsive micelles for applications in selective drug delivery, sensing, and surface patterning. PMID- 17343290 TI - Controlling polymer properties through dynamic metal-ligand interactions: supramolecular cruciforms made easy. AB - A straightforward methodology towards the supramolecular synthesis of novel organometallic polymers with attractive optical properties is presented. By coordinating bifunctional fluorescent cruciform molecules through ditopic metalated pincer complexes (Pd or Pt), we have synthesized a new class of well defined coordination polymers that have controllable and tunable physical and photophysical properties. The formation of these new materials by employing metal coordination was monitored by (1)H NMR spectroscopy, the association strength of the metal-ligand interaction was measured by isothermal titration calorimetry, the solution polymeric properties were evaluated by viscometry, and the optical properties were measured and observed by fluorescence spectroscopy. The fast and quantitative synthesis of a wide range of prefabricated monomeric cruciform and metalated-pincer-complex components will allow for the rapid generation, growth, and optimization of this new class of functional polymers, which have potential electronic and optical applications. PMID- 17343292 TI - Comparison of behavioral and psychological symptoms in early-onset and late-onset Alzheimer's disease. AB - BACKGROUND: When comparing with early-onset Alzheimer's disease (EO-AD) and late onset Alzheimer's disease (LO-AD), some symptomatological differences in clinical features can be seen between them. Rapid progression, more severe language problems or visuospatial dysfunction occur more often in EO-AD patients. However, there have been very few reports about the differences in behavioral and psychological symptoms between these two groups. AIM: The aim of this study was to demonstrate the differences in behavioral symptoms between EO-AD and LO-AD groups. METHOD: Three hundred and seven consecutive outpatients with AD were put into an EO-AD group (46 patients) or a LO-AD group (261 patients). Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment. RESULTS: Significant differences were found between the EO-AD and LO-AD groups in terms of NPI total score (EO-AD: 10.3 +/- 10.9, LO-AD: 17.8 +/- 17.0, p = 0.004) and number of patients who experienced each NPI subscale score (delusion; EO-AD: 13.0%, LO-AD: 50.6%, p < 0.001). There were no differences in cognitive functions or dementia severity between two groups. CONCLUSION: In EO-AD, behavioral and psychological symptoms are relatively fewer than LO-AD at the first medical assessment. PMID- 17343293 TI - Markers of inflammation and cognitive decline in an African-Caribbean population. AB - BACKGROUND: Inflammatory processes may play an important role in cognitive decline and dementia. We investigated the prospective association between levels of three markers of inflammation, plasma interleukin-6 (IL-6), serum C-reactive protein (CRP), serum amyloid A (SAA), and cognitive decline in an African Caribbean community population. METHODS: Of 290 participants aged 55-75 years at baseline sampled from Primary Care registration lists in south London, 216 (75%) were re-interviewed after 3 years. Baseline plasma concentrations of IL-6, CRP and SAA were ascertained through immunoassays. A battery of psychometric tests was administered on both occasions and decline in both individual tests and a composite outcome was analysed. RESULTS: After adjustment for potential confounding factors, raised levels of IL-6 (>3.1 pg/ml) were associated with cognitive decline in the total sample (odds ratio 2.9, 95% CI 1.1-7.5), but no associations were found for CRP or SAA. Raised IL-6 was most strongly associated with decline in orientation and immediate verbal recall tasks, with weaker associations for delayed recall and psychomotor speed. CONCLUSIONS: Raised IL-6 but not CRP predicted cognitive decline in this population Inflammatory changes associated with cognitive decline may be specific to particular causal pathways. PMID- 17343294 TI - Fractional anisotropy and mean diffusivity: comparison between 3.0-T and 1.5-T diffusion tensor imaging with parallel imaging using histogram and region of interest analysis. AB - We performed a comparison study focusing on differences in fractional anisotropy (FA) and mean diffusivity (MD) between 3-T and 1.5-T diffusion tensor imaging (DTI) with parallel imaging. Thirty healthy volunteers underwent DTI with an eight-channel phased-array coil at both 3 T and 1.5 T. Histogram and region of interest (ROI) analyses were performed. Paired t tests were applied for statistical analysis. Signal-to-noise ratios of these regions were also measured. For histogram analysis, peak location of FA was significantly lower at 3 T than at 1.5 T (P = 0.04). Mean FA was significantly higher at 3 T than at 1.5 T (P = 0.002). Peak location of MD was significantly lower at 3 T than at 1.5 T (P < 0.001). Mean MD was significantly lower at 3 T than at 1.5 T (P < 0.001). In ROI analysis, FA was significantly larger at 3 T than at 1.5 T in the centrum semiovale (P < 0.001), middle cerebellar peduncle (P < 0.001), cerebral peduncle (P = 0.006), posterior limb of the internal capsule (P = 0.007), genu (P < 0.001) and splenium (P < 0.001). FA was significantly lower at 3 T than at 1.5 T in the globus pallidus (P < 0.001). MD was significantly smaller at 3 T than at 1.5 T in the globus pallidus (P = 0.007), thalamus (P < 0.001), centrum semiovale (P < 0.001), middle cerebellar peduncle (P < 0.001), cerebral peduncle (P = 0.01), posterior limb of the internal capsule (P < 0.001), genu (P = 0.01) and splenium (P < 0.001). Significant differences in FA and MD exist between 3 T and 1.5 T for whole-brain histogram analysis and ROI analysis. PMID- 17343295 TI - Cell-autonomous control of interferon type I expression by indoleamine 2,3 dioxygenase in regulatory CD19+ dendritic cells. AB - Following CD80/86 (B7) and TLR9 ligation, small subsets of splenic dendritic cells expressing CD19 (CD19(+) DC) acquire potent T cell regulatory functions due to induced expression of the intracellular enzyme indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan. In CD19(+) DC, IFN type I (IFN-alpha) is the obligate inducer of IDO. We now report that IFN-alpha production needed to stimulate high-level expression of IDO following B7 ligation is itself dependent on basal levels of IDO activity. Genetic and pharmacologic ablation of IDO completely abrogated IFN-alpha production by CD19(+) DC after B7 ligation. In contrast, IDO ablation did not block IFN-alpha production by CD19(+) DC after TLR9 ligation. IDO-mediated control of IFN-alpha production depended on tryptophan depletion as adding excess tryptophan also blocked IFN-alpha expression after B7 ligation. Consistent with this, DC from mice deficient in general control of non-derepressible-2 (GCN2)-kinase, a component of the cellular stress response to amino acid withdrawal, did not produce IFN-alpha following B7 ligation, but produced IFN-alpha after TLR9 ligation. Thus, B7 and TLR9 ligands stimulate IFN-alpha expression in CD19(+) DC via distinct signaling pathways. In the case of B7 ligation, IDO activates cell-autonomous signals essential for IFN alpha production, most likely by activating the GCN2-kinase-dependent stress response. PMID- 17343296 TI - Education in musculoskeletal health--how can it be improved to meet growing needs? PMID- 17343297 TI - Curriculum design: finding a balance. PMID- 17343298 TI - Rheumatoid arthritis and diabetes mellitus: evidence for an association? PMID- 17343299 TI - Is minimal clinically important difference relevant for the interpretation of clinical trials in pediatric rheumatic diseases? PMID- 17343300 TI - Role of thrombotic and fibrinolytic alterations in the pathogenesis and treatment of osteonecrosis. PMID- 17343301 TI - A model to estimate health utilities index mark 3 utility scores from WOMAC index scores in patients with osteoarthritis of the knee. AB - OBJECTIVE: To develop a formula to translate Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores collected in clinical trials of patients with osteoarthritis (OA) into Health Utilities Index Mark 3 (HUI3) utility scores for application in economic evaluation. METHODS: Data from a previously published open-label randomized controlled trial of appropriate care with hylan G-F 20 versus appropriate care without hylan G-F 20 in 255 outpatients with knee OA. We estimated linear regression models of HUI3 scores using various functions of WOMAC, demographics, and clinical variables. Out-of-sample predictive performance of the models was assessed using the mean absolute error and several other criteria. RESULTS: The preferred formula included WOMAC pain, stiffness, function subscales, demographic variables; it accounted for almost 40% of the variation in the HUI3 utility scores. At the group level, absolute differences between predicted and actual overall HUI3 utility scores were < 0.001 and not statistically significantly different from zero. CONCLUSION: A formula was derived from the WOMAC index to estimate overall utility scores based on the HUI3 for studies of patients with OA for whom utility has not been recorded. Researchers can estimate overall utility scores, compute quality-adjusted life years, and perform cost-utility analyses within a defined range of certainty. PMID- 17343302 TI - Tramadol for osteoarthritis: a systematic review and metaanalysis. AB - OBJECTIVE: Tramadol is increasingly used for the treatment of osteoarthritis (OA) because it does not produce gastrointestinal bleeding or renal problems and does not affect articular cartilage. We sought to determine the analgesic effectiveness, the effect on physical function, the duration of benefit, and the safety of oral tramadol in people with OA. METHODS: We searched the Cochrane Central Register of Controlled Trials (Central), Medline, Embase, and Lilacs databases up to August 2005. We included randomized controlled trials (RCT) that evaluated the effect of tramadol or tramadol plus paracetamol on pain levels and/or physical function. No language restriction was applied. RESULTS: We included 11 RCT with a total of 1019 participants who received tramadol or tramadol/paracetamol and 920 participants who received placebo or active control. Participants who received tramadol reported (1) less pain [-8.5 units on a 0-100 scale; (95% CI -12.0 to -5.0)], a 12% relative decrease in pain intensity; (2) higher degree of global improvement: one of every 6 individuals taking tramadol or tramadol/paracetamol exhibited at least moderate global improvement (95% CI 4 to 9); and (3) improvement in stiffness and function, an 8.5% relative improvement in Western Ontario and McMaster University Osteoarthritis Index score, than patients who received placebo. In terms of adverse events, one of every 5 participants who received tramadol or tramadol/paracetamol experienced minor adverse events and one of every eight stopped taking the medication because of adverse events (95% CI 7 to 12) compared to participants who received placebo. CONCLUSION: Tramadol or tramadol/paracetamol decreases pain intensity, produces symptom relief, and improves function in patients with OA, but these benefits are small. PMID- 17343303 TI - Mycophenolate mofetil and intravenous dexamethasone in the treatment of persistent lupus myelitis. AB - Methylprednisolone and cyclophosphamide pulse therapies are the most commonly used for transverse myelopathy in neuropsychiatric lupus. Little is known about the efficacy of other immunosuppressors. We describe the case of a 33-year-old woman with systemic lupus erythematosus, who developed a tranverse myelopathy, beginning with a hiccup due to involvement of the medulla oblongata; despite pulses of methylprednisolone plus azathioprine and cyclosporine therapy, she developed paraparesis with involvement of the cervical spine cord. After oral cyclophosphamide, the lesion remained active. Subsequent therapy with mycophenolate mofetil and continuous intravenous infusions of dexamethasone resulted in reduction of the lesion's size, disappearance of magnetic resonance imaging enhancement, and a complete recovery. PMID- 17343304 TI - Rapid acetabular osteolysis secondary to subchondral insufficiency fracture. AB - A 93-year-old man presented with a one-month history of persistent left hip pain of sudden onset. At first visit, radiographs revealed a fracture line at the medial portion of the acetabulum with no displacement. Magnetic resonance imaging revealed bone marrow edema in the corresponding medial portion of the acetabulum. Radiographs obtained 2 months later showed rapid acetabular osteolysis with associated prominent migration of the femoral head into the acetabulum. Histology obtained from the hip joint was consistent with a subchondral insufficiency fracture with no evidence of massive chondrolysis. Our case was considered as a subchondral insufficiency fracture of the left acetabulum resulting in rapid acetabular osteolysis (protrusio acetabuli). PMID- 17343305 TI - Joint destruction in septic arthritis. PMID- 17343306 TI - The World Health Organisation International Classification of Functioning, Disability and Health: a conceptual model and interface for the OMERACT process. AB - "What to measure" refers to domains stable over time. "How to measure" is constantly evolving. Lacking a common terminology and common underlying conceptual model of functioning and disability, what and how to measure have been described differently in the various OMERACT Core Sets. With the approval of the International Classification of Functioning, Disability and Health (ICF) by the World Health Assembly in 2001, we now have a universally conceptual model that integrates the biomedical and societal model of functioning and disability. The so-called ICF Core Sets can be used as a basis for the further specification of OMERACT domains addressing aspects of functioning. In line with the successful approach taken by OMERACT, it is suggested to comprehensively specify the domain "function" when defining "what should be measured," and only then to recommend how to measure or which health status measure to use. We recommend comparing the specifications of domains addressing aspects of functioning of OMERACT Core Sets already established with the ICF Core Sets, and examine whether the ICF Core Sets may be useful for the further specification of these domains. PMID- 17343307 TI - Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema. AB - OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. METHODS: After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval. PMID- 17343308 TI - Simulation studies of surrogate endpoint validation using single trial and multitrial statistical approaches. AB - OBJECTIVE: A schema was recently proposed for assessing the levels of evidence for surrogate validity that included 4 domains: Target, Study Design, Statistical Strength, and Penalties. This report examines one component of the schema. It surveys the literature on methods of statistical validation of surrogate markers and compares these methods head-to-head using simulated datasets. METHODS: Simulated datasets (continuous, multivariate normal) were generated to capture 3 possible relationships of surrogate (S) and true (T) outcome (none, weakly positive, strongly positive) each applied to 4 treatment effects (effect on both surrogate and true outcome, effect on neither, effect on surrogate only, and effect on true outcome only). These datasets were analyzed using single and multitrial statistical approaches, and the results were provided to participants for discussion. RESULTS: The multitrial surrogate threshold effect seemed to capture best the requirement that surrogate validation is demonstrated by a treatment-associated change in the surrogate predicting a treatment-associated change in the outcome. CONCLUSION: There was general agreement that neither a single trial nor any of the single trial statistical methods was adequate to establish surrogate validity. These exercises also showed that summary statistics developed specifically to establish surrogate validity, such as the proportion of the effect explained, were problematic. A sizable statistical research agenda remains, which includes investigating the additional advantage obtained with modeling subject-level data compared to modeling with only trial-level data; and developing and testing multitrial statistical approaches robust to settings with only a few trials. PMID- 17343309 TI - Synovial macrophages as a biomarker of response to therapeutic intervention in rheumatoid arthritis: standardization and consistency across centers. AB - Successive studies from one academic center (Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands) have consistently suggested that synovial tissue expression of sublining macrophages may be a biomarker of clinical response to therapeutic intervention in rheumatoid arthritis (RA) clinical trials. A proof-of-concept, randomized clinical trial was completed at a second academic center (St. Vincent's University Hospital, Dublin, Ireland), and the relationship between the change in disease activity and the change in sublining macrophages in distinct treatment cohorts was determined. The preliminary findings were not conclusive, but appeared to support a role for sublining CD68+ macrophages as a biomarker of clinical response to therapeutic intervention in cohorts of patients with RA. PMID- 17343310 TI - Testing of the preliminary OMERACT validation criteria for a biomarker to be regarded as reflecting structural damage endpoints in rheumatoid arthritis clinical trials: the example of C-reactive protein. AB - OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker extensively studied in RA, was then used to test these criteria. Our objectives were: (1) To assess the strength of evidence in support of CRP as a soluble biomarker reflecting structural damage in RA according to the draft validation criteria. (2) To assess the strength of recommendation for inclusion of individual criteria in the draft set. METHODS: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants in a special interest soluble biomarker group at OMERACT 8. Participants at OMERACT 8 were asked to rate the strength of evidence and the strength of the recommendation in support of each individual criterion on a 0-10 numerical rating scale. Working group members not present at OMERACT voted by a Web-based survey. RESULTS: Minimal data were extracted from the literature pertaining to those criteria listed under the category of truth. Ratings for strength of evidence were moderate to low (< 7) for CRP as a biomarker reflecting structural damage in RA; this was true for all criteria except those listed under the category of feasibility and 2 listed under the category of discrimination pertaining to assay reproducibility and evidence regarding sources of variability. Ratings for strength of recommendation for inclusion of each of the 14 criteria in the draft set were high (> 7) except for those criteria listed under the category of truth. CONCLUSION: The draft criteria serve as a useful template in the evaluation of the strength of evidence in support of a particular soluble biomarker as reflecting structural damage in RA. PMID- 17343311 TI - Development of draft validation criteria for a soluble biomarker to be regarded as a valid biomarker reflecting structural damage endpoints in rheumatoid arthritis and spondyloarthritis clinical trials. AB - OBJECTIVE: Recent work has shown that several soluble biomarkers, detectable in peripheral blood, synovial fluid, and/or urine, reflect remodeling of joint tissues and may therefore constitute outcome measures that reflect joint damage. Consequently, it is now desirable to begin the process of developing criteria for validation of a soluble biomarker as an outcome measure reflecting structural damage progression in trials of disease-modifying therapies for rheumatoid arthritis (RA) and spondyloarthritis (SpA). Our objective was to develop validation criteria for a soluble biomarker to be regarded as a valid biomarker reflecting radiological endpoints in RA and SpA clinical trials. METHODS: A special interest group was established comprising investigators with expertise in soluble biomarker assay development as well as in outcomes research. This project was initiated by means of a Delphi consensus exercise. A list of draft criteria was first generated following a review of a US National Institutes of Health (NIH) 2000 white paper (available at: http://www.niams.nih.gov/ne/oi/ oabiomarwhipap.htm) that focused on biomarkers in OA, and these were organized under subject headings relevant to the OMERACT filter: truth, discrimination, and feasibility. Additional criteria were solicited from the working group. This was followed by 3 rounds of voting. RESULTS: A list of 31 criteria was generated prior to voting. The first 2 rounds of voting resulted in cumulative agreement that 19 criteria be retained and 4 discarded, while discrepancies were recorded for 8 criteria. In the third round of voting, cumulative agreement was achieved to retain 5 of the 8 discrepant criteria, so that the final list included 24 criteria. CONCLUSION: A draft set of criteria for validation of a soluble biomarker to be regarded as reflecting radiological damage endpoints in clinical trials has been proposed on the basis of consensus. PMID- 17343312 TI - Assessing single joints in arthritis clinical trials. AB - Endpoints and outcome measurements to detect changes in joint structure for the assessment of single joints are needed to enable rheumatology clinical trials of therapies targeting preservation of joint structure, especially via locally applied therapies. While the assessment of certain aspects of single joint inflammation and function is accepted in the evaluation of osteoarthritis (OA) using the WOMAC, it tends to be limited to the knee and hip. The advent of therapies that are directed toward a single joint in inflammatory arthritis, including intraarticular cytokine antagonists and gene therapeutics, requires reliable measures to assess change over time in single joints and the clinical meaningfulness of such change. Traditionally, clinical trials for inflammatory arthritis have used composite response indices such as American College of Rheumatology response or improvement in Disease Activity Score as outcomes based on multiple joint clinical measures, acute phase reactants, and functional status. However, it is not known whether these will appropriately detect changes referable to single joint intervention. This Special Interest Group was developed to bring together interested individuals to identify and evaluate outcome measurements for single joints. The knee was the initial focus, as clinical, radiographic, and functional assessments have been well developed for knee OA. A PubMed English language review was conducted before OMERACT 8, evaluating existing clinical instruments in the context of the OMERACT filter. At OMERACT 8, the group developed a research agenda to perform additional validation studies of clinical and functional indices, imaging, synovial histopathology, and soluble biomarkers. PMID- 17343313 TI - Sarcoid-like granulomatous disease following etanercept treatment for RA. PMID- 17343314 TI - C-reactive protein in primary antiphospholipid syndrome. PMID- 17343315 TI - Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. AB - OBJECTIVE: Macrophage activation syndrome (MAS) is a well described, but purportedly uncommon manifestation of systemic juvenile idiopathic arthritis (SJIA). There is evidence to suggest that macrophage activation is integral to the pathogenesis of SJIA. Accordingly, many patients with SJIA may have evidence of mild MAS that is not appreciated clinically. We investigated the prevalence of occult MAS in children with SJIA by reviewing bone marrow aspirates (BMA). METHODS: Patients diagnosed with SJIA who underwent bone marrow aspiration were identified retrospectively. Patients admitted with a diagnosis of fever of unknown origin and discharged with a diagnosis other than SJIA or malignancy, and who had a BMA, were identified as controls. The BMA were reviewed by a single hematopathologist for evidence of MAS, ranging from activated macrophages to frank hemophagocytic cells. RESULTS: Eight of 15 (53%) patients with SJIA had BMA suggestive of MAS. Two of 15 patients (13%) were diagnosed clinically with MAS. Three patients (20%) were noted to have frank hemophagocytosis, only one of whom was diagnosed with MAS clinically. There were no statistically significant differences in the laboratory values for the patients with and without evidence of MAS on BMA. There was no evidence of increased macrophage activity or hemophagocytosis in any of the control BMA. CONCLUSION: Occult MAS appears to be common in patients with SJIA who undergo BMA. This suggests that macrophage activation may be integral to the pathogenesis of SJIA, with implications for treatment. PMID- 17343316 TI - Interleukin 18 as a marker of disease activity and severity in patients with juvenile idiopathic arthritis. AB - OBJECTIVE: To verify the importance of interleukin 18 (IL-18) in the pathogenesis of juvenile idiopathic arthritis (JIA). We measured IL-18 levels in synovial fluid (SF) and serum, and determined their correlation with measures of disease activity and severity. METHODS: Fifty patients with JIA (13 systemic, 13 polyarticular, 24 oligoarticular) and 25 matched controls were analyzed. Cytokine levels (IL-1beta, IL-1Ra, IL-6, and IL-18) were quantified in serum and SF by ELISA, and disease activity measures were evaluated immediately after knee articular puncture. Radiological assessment was made according to the Steinbrocker method. Statistical analysis was performed by Spearman's rank-order correlation and Mann-Whitney rank test. RESULTS: All the analyzed cytokine levels (IL-1, IL-1Ra, IL-6, and IL-18) were higher in patients' sera than in controls. Remarkably, in patients with JIA, IL-18 SF levels did not differ from those of serum; they were positively correlated. The levels of IL-18 (SF and serum) were positively correlated with measures of disease activity: C-reactive protein, number of active joints, and radiological score, as well as with levels of IL-1, IL-1Ra, and IL-6. Moreover, IL-18 and IL-6 levels in SF and serum were much higher in patients with systemic disease compared to the other types of disease onset. In contrast, IL-1 and IL-1Ra were not different among JIA subtypes. CONCLUSION: Our results strongly suggest the participation of IL-18 in the pathophysiology of JIA. The positive correlation of this cytokine with several measures of articular inflammation and disease severity suggests that IL-18 could be a better target for the treatment of arthritis. PMID- 17343317 TI - Prevalence and outcome of juvenile idiopathic arthritis-associated uveitis and relation to articular disease. AB - OBJECTIVE: To determine prevalence and complications of juvenile idiopathic arthritis (JIA)-associated uveitis, and to evaluate risk factors for uveitis and its relation to articular disease. METHODS: Records of 309 patients with JIA (244 female, 65 male, mean age at onset 4.9 yrs) were retrospectively reviewed. Occurrence of uveitis and complications were assessed among oligoarticular-onset JIA (193 patients), polyarticular-onset JIA (66 patients), and systemic-onset JIA (50 patients). The presence of antinuclear antibodies (ANA) was determined in patients with oligoarticular-onset JIA. Therapy and relapses of uveitis and arthritis were recorded at each visit during the followup (mean followup 7.6 yrs). RESULTS: Sixty-two patients developed uveitis (20.1%); 57 patients had oligoarticular-, 3 polyarticular-, and 2 systemic-onset JIA. Uveitis was asymptomatic in 56/62 cases. Fifty-five of the 62 patients (88.7%) developed uveitis within 4 years from disease onset. In patients with oligoarticular-onset JIA, an early age at disease onset and the presence of ANA (p < 0.05) and DRB1*11 (p < 0.03) were the best predictors of uveitis, while a polyarticular course was not associated to uveitis (p > 0.05). Active arthritis was present at the first episode of uveitis in 46/62 patients. Forty-four of the 62 patients experienced relapses of uveitis: in 20/62, relapses were concomitant to arthritis relapses; in 24/62 relapses presented without active arthritis. Complications of uveitis developed in 35.5% of the patients (22/62), leading to visual impairment in 13 patients. CONCLUSION: Current guidelines provide early identification of uveitis in 90% of patients. With the exception of the first episode of uveitis, uveitis and arthritis seem to run different courses; close ophthalmologic scrutiny then should also be maintained during arthritis remission. PMID- 17343318 TI - Tumor necrosis factor-alpha blocker in treatment of juvenile idiopathic arthritis associated uveitis refractory to second-line agents: results of a multinational survey. AB - OBJECTIVE: Uveitis occurs in 10%-15% of patients with juvenile idiopathic arthritis (JIA). If topical treatment fails, second-line agents are used to control the disease. However, some patients need the addition of tumor necrosis factor-alpha (TNF-alpha) antagonist (anti-TNF). We organized a cross-sectional cohort to investigate use and efficacy of anti-TNF treatment in patients with JIA associated uveitis. METHODS: The international pediatric rheumatology community was queried about the use and efficacy of anti-TNF in treatment of JIA-associated uveitis using an E-mail survey. RESULTS: Of the 33 responding centers following 884 patients with uveitis, only 15 centers, following 404 patients, were using anti-TNF for this indication. A total of 47 patients with JIA-related uveitis treated with anti-TNF because of an insufficient response to previous therapy were reported. The mean age of the patients was 12.5 years. The mean duration from onset of uveitis to start of anti-TNF treatment was 45.1 months. Three different anti-TNF agents were used: etanercept in 34 cases, infliximab in 25 cases, and adalimumab in 3 cases. In 12 of the 34 patients etanercept was inefficacious and patients were switched to infliximab. The final response was rated according to a composite index as 53%/12%/32%, and according to physician rating as 47%/12%/38% representing good, moderate, and poor, respectively, in the etanercept group; and 70%/30%/0% and 68%/24%/0% in the infliximab group. All 3 patients taking adalimumab were responders. Infliximab was statistically significantly more efficacious for the treatment of JIA-associated uveitis than etanercept (chi-square p = 0.004). CONCLUSION: Anti-TNF seems to be an effective treatment for refractory JIA-associated uveitis. In this cohort infliximab was more efficacious than etanercept. PMID- 17343319 TI - Does self-management lead to sustainable health benefits in people with arthritis? A 2-year transition study of 452 Australians. AB - OBJECTIVE: To evaluate the Arthritis Self-Management Course (ASMC) when applied in a nationwide context. METHODS: Four hundred fifty-two people who participated in the ASMC across Australian states took part in a longitudinal followup study. ASMC is a 6 week, 2 h group educational program designed to assist people with chronic illness to better manage their condition. Measures of program effectiveness included health status and service utilization. Data were collected on 3 occasions: before intervention (baseline) and 6 months and 2 years after the program. RESULTS: Several indicators of health status showed improvement at 6 months following the ASMC. These included reduction in pain (4%; p < 0.001), fatigue (3%; p < 0.01), and health distress (12%; p < 0.001) as well as increase in self-efficacy (6%; p < 0.001). Increased self-efficacy was a significant predictor of positive change in health status. Health-related behaviors such as aerobic exercise also increased, with the proportion of people who did little or no exercise decreasing by up to 8%. These changes were sustained at 2 years. There was an increase in use of analgesics at 6 months and an increase in use of nonsteroidal antiinflammatory drugs at 2 years. No changes in healthcare utilization (physician visits, allied health visits, and hospitalizations) were observed. CONCLUSION: The ASMC is a widely applied program in which participants benefit through a reduction in pain, fatigue, and health distress. Although the absolute changes in health status are small, the low cost and wide application of the intervention suggests the program may have a substantial public health effect. PMID- 17343320 TI - Hand dominance in upper extremity musculoskeletal disorders. AB - OBJECTIVE: To investigate the role of hand dominance in common upper extremity musculoskeletal disorders (UEMSD) in a population study. METHODS: The target population consisted of a representative sample of people aged 30 years or older residing in Finland during 2000-2001. Of the 7977 eligible subjects, 6254 (78.4%) were included in the study. RESULTS: The prevalence of UEMSD was as follows: rotator cuff tendinitis 3.8%, bicipital tendinitis 0.5%, lateral epicondylitis 1.1%, medial epicondylitis 0.3%, carpal tunnel syndrome (CTS) 3.8%, and surgery due to CTS 1.3%. CTS was 2.5 times as prevalent in women as men, whereas the other UEMSD were as common in both sexes. Rotator cuff and bicipital tendinitis and medial epicondylitis were more prevalent in the dominant arm only in women, whereas lateral epicondylitis was more prevalent in the dominant elbow in both sexes. The higher prevalence of rotator cuff and bicipital tendinitis in the dominant side persisted beyond working age. The prevalence of CTS did not differ by hand dominance. Dominant hand had been operated more frequently for CTS in women. CONCLUSION: Our findings show that UEMSD are more prevalent in the dominant than nondominant arm mainly in women. For shoulder tendinitis, the difference persists throughout adult age. Physical load factors may have long lasting effects on the shoulder and they may play a greater role in women than men. PMID- 17343321 TI - Inflammatory and structural evaluation in spondyloarthritis: magnetic resonance imaging analysis of axial and peripheral involvement. AB - OBJECTIVE: To determine the magnetic resonance imaging (MRI) criteria of most value in the assessment of patients with spondyloarthropathy (SpA) with axial or peripheral involvement. METHODS: Fat suppressed (FS)-T2 and pre- and postinjection FS-T1 images were obtained in the most symptomatic region (axial or peripheral) of patients requiring tumor necrosis factor-a blockers. Thirty-eight MRI (21 axial and 17 peripheral) were blindly scored at synovial (S) and entheseal (E) sites by 2 experienced observers screening for 7 inflammatory and 7 structural predefined criteria, which were evaluated for frequency (N) and intra- and interobserver reproducibility. RESULTS: In peripheral regions, synovitis (S; N = 69.4%), ligament inflammation (E; N = 39.7%), bone marrow edema (S; N = 22.1%; E; N = 15%), and tenosynovitis (S; N = 21%) were recorded with good to excellent intraobserver reproducibility [intraclass correlation coefficient (ICC) 0.49-0.93] and moderate to good interobserver reproducibility (ICC 0.49-0.66). With regard to structural criteria, erosions (S; N = 17.1%) and enthesophytes (E; N = 13.9%) exhibited good to excellent intraobserver (ICC 0.71-0.85) and moderate interobserver reproducibility (ICC 0.54-0.49); the reproducibility of fat inflation (N = 1.4%) was good (ICC 0.76-0.78). In axial regions, no inflammatory criteria achieved good interobserver reproducibility. However, fat inflation (S; N = 86%), chondral lesions (S; N = 85.8%), enthesophytes (E; N = 76.7%), fusion (S; N = 41.2%), and erosions (S; N = 25.1%) showed excellent intraobserver reproducibility (ICC 0.81-0.98), and moderate to excellent interobserver reproducibility (ICC 0.50-0.96). CONCLUSION: In terms of intra- and interobserver reproducibility, MRI is a reliable tool with which to assess synovitis, bone edema, ligament inflammation, tenosynovitis, erosion, enthesophytes, and fat inflation in patients with peripheral involvement. In those with axial involvement, inflammatory criteria lack interobserver reproducibility, but chondral lesions, erosion, fat inflation, fusion, and enthesophytes are relevant. PMID- 17343322 TI - The influence of illness and variables associated with functional limitations in Chinese patients with ankylosing spondylitis. AB - OBJECTIVE: To assess the effect of illness and the functional outcome of Chinese patients with ankylosing spondylitis (AS), and to identify variables associated with a poor functional outcome. METHODS: A cross-sectional study was performed in 314 patients with AS who participated in a postal survey on the effects of illness on work capacity, functional limitations, and explanatory variables. Functional limitations were assessed using the Bath AS Functional Index (BASFI). Explanatory variables included sociodemographic characteristics and clinical features. Linear regression analyses were performed to identify variables associated with functional impairment. RESULTS: The mean +/- standard deviation (SD) age of the patients was 44 +/- 11 years, with a mean disease duration of 19 +/- 11 years. The median BASFI was 3 (IQR 1.0-5.3). Twenty-three percent reported AS-related work disability after a median of 11 (IQR 2-17) years. Multivariate analysis identified low family income, education level, disease duration, Bath AS Disease Activity Index (BASDAI) score, and patient's global score as factors associated with functional impairment. In the subgroup of patients with disease duration < 20 years, low monthly income, juvenile onset, and high patient global score were associated with functional impairment; whereas in the subgroup of patients with disease duration > or = 20 years, less education, longer disease duration, and history of peripheral joint pain were associated with functional impairment. BASDAI was associated with functional impairment in both subgroups. CONCLUSION: AS in Chinese patients had significant social and economic impact. Poor socioeconomic background, long disease duration, and high disease activity level were associated with functional impairment. PMID- 17343324 TI - Gene therapy of cancer. AB - The original concept of gene therapy was the introduction of a healthy copy of gene into an ill human cell in order to correct gene defects in monogenic hereditary diseases. Since then the idea of gene therapy was expanded to cure or slow down the progression of numerous inherited and acquired diseases. Presently, there are 918 ongoing gene therapy clinical trials worldwide. The major indication in these trials is cancer (608 trials or 66% of the total number). Gene therapy of cancer can be defined as transfer of nucleic acids into tumor or normal cells aiming at eradicating or reducing the tumor mass by direct killing of cells, immunomodulation or correction of genetic errors and reversion of the malignant status. Initially started with lots of optimism and enthusiasm, cancer genet therapy has shown limited success in the treatment of patients. This lesson highlights current limitations and almost endless possibilities of cancer gene therapy. The major difficulty in advancing gene therapy technology for the lab bench to clinical practice is the problem with gene delivery vehicles (so-called vectors) needed to ferry genetic material into a cell. Despite few reports of therapeutic responses in some patients, there is still no proof of clinical efficacy of most cancer gene therapy approaches, primarily due to very low transduction and expression efficacy in vivo of available vectors. An "ideal" gene therapy vector should: be administered through a noninvasive route; target not only the primary tumor mass but disseminated tumor cells and micrometastases at distant and unreachable sites as well; carry a therapeutic gene with tumor restricted and time-regulated and sustained expression. Current strategies for combating cancer with gene therapy can be subdivided into 4 basic concepts: 1) replacement of missing tumor suppressor gene and/or blocking of oncogenes or proinflammatory genes; 2) suicide gene strategies; 3) induction of immune mediated destruction; and 4) inhibition of tumor angiogenesis. Clinical advance will probably come first from cooperation with standard cancer treatment such as chemotherapy, radiotherapy and immunotherapy. PMID- 17343323 TI - Ligands for programmed cell death 1 gene in patients with systemic lupus erythematosus. AB - OBJECTIVE: To investigate the role of ligands for programmed cell death 1 (PD-L) in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: One hundred sixty-four patients with SLE and 160 healthy controls were enrolled in our study. The PD-L1 and PD-L2 polymorphisms were determined by polymerase chain reaction (PCR)/direct sequencing or restriction fragment length polymorphism (RFLP)-PCR. RESULTS: The genotype distributions of PD-L2 47103 C/T polymorphisms in patients with SLE were significantly different from those of the controls (p = 0.003). The genotype frequency of PD-L2 47103 T/T, in comparison with 47103 C/C, was significantly increased in patients with SLE when compared with that of the controls (odds ratio 2.5, 95% confidence interval 1.4-4.4, p = 0.001). A similar finding could also be found in the allele frequency of PD-L2 47103 T (SLE vs control, OR 1.7, 95% CI 1.3-2.4, p = 0.001). There were no significant differences in the genotype and allele frequencies of PD-L1 polymorphisms between the patients and controls. CONCLUSION: PD-L2 47103 T may be associated with susceptibility to SLE in Taiwan. PMID- 17343325 TI - Adjuvant chemotherapy of breast cancer. AB - Breast cancer is the most common cancer and the second most common cause of cancer-related death in women. The last three decades have yielded marked progress in the diagnosis and management of breast cancer. Not only is the disease being detected at a much earlier stage, but the addition of systemic therapy has also improved survival. Cyclophosphamide (C), methotrexate (M) and 5 fluorouracil (F)(CMF) combination chemotherapy was among the first chemotherapy regimens found to prolong both disease-free survival (DFS) and overall survival (OS) when given in the adjuvant setting. The 2000 Oxford overview confirmed that anthracycline-based chemotherapy offers a survival advantage compared with CMF. Anthracycline-based therapies are better tolerated in terms of acute side effects but long-term sequels (cardiotoxicity, secondary leukaemia) are worrisome. It seems that more intensive three-drug regimens (FE[epirubicin](100)C, CEF, CA[adriamycin]F,) or the combination of E+CMF are more active in reducing the risk of relapse and death in breast cancer patients. The reported trials with taxanes demonstrated comparable reduction in the risk of recurrence and death, although administration of paclitaxel (T)-containing regimens appears to be most effective if administered on an every-2-week schedule with granulocyte colony stimulating factor (G-CSF). The risk of febrile neutropenia is highest for the TAC regimen (~25%), although other trials have demonstrated that use of G-CSF will reduce this complication to about 3%. PMID- 17343326 TI - Cancer cachexia and immunomodulation. AB - Cachexia is derived from the Greek words "kakos" meaning "bad" and "hexis" meaning "condition". Cachexia is a debilitating state of involuntary weight loss complicating malignant, infectious and inflammatory diseases. Several hypotheses for its etiology have been suggested including cytokines, circulating hormones, neuropeptides, neurotransmitters, and tumor-derived factors. Cachexia syndrome is caused predominantly by cytokines either produced by cancer or released by the immune system cells as a response to the presence of cancer, as well as other tumor products that induce profound lipolysis or protein degradation. Several strategies have been applied in the management of cachexia and related immunodeficiency including: 1.hypercaloric feeding;2.administration of glucocorticoids;3.progrestational drugs;4.cyproheptadine and other antiserotonergic drugs;5.branched-chain aminoacids;6.prokinetic agents;7.eicosapentanoic acid (EPA);8.cannabinoids;9.5'-deoxy-5 fluorouridine;10.emerging drugs: melatonin, thalidomide, beta2-agonists, non steroidal anti-inflammatory drugs (NSAIDs);11.others:pentoxifylline, hydrazine sulfate, anabolic steroids. Better understanding of the mechanisms underlying cancer and cachexia leading to immune dysfunction has guided immunomodulatory strategies to reverse cachexia and immunodeficiency. The oncept is that the tumor itself may lead to cachexia and immune dysfunction but also cachexia is related and mediated with immune dysfunction. Thus the purpose is to affect the tumor itself and cachexia immune pathways in order to restore immune efficiency. However, more experimental and clinical studies are needed to evaluate the efficacy of immunomodulatory intervention in cancer cachexia and related immunodeficiency. PMID- 17343327 TI - Colorectal cancer care in the Balkan countries. AB - PURPOSE: The aim of this survey was to assess the status of colorectal cancer (CRC) care in the Balkans by contacting cancer care specialists in the Balkan Union of Oncology (BUON) member states. MATERIALS AND METHODS: The authors searched the 2004 membership directories of the ASCO and ESMO and identified members from the Balkan countries. They then sent them a 3-page questionnaire via e-mail or fax. RESULTS: Fifty-two responses from 8 countries were received and analysed. The response rate varied from 25% (Turkey) to 3% (Bulgaria). No Bosnian (n=13), Croatian (n=16) and Albanian (n=1) participated. The results showed that, despite variations on the state of development among Balkan countries, there were some striking similarities and also some similar difficulties that CRC specialists are facing in their individual countries. CONCLUSION: Combined and coordinated efforts at solving some of these common problems may help CRC patients receive better and higher quality care. PMID- 17343328 TI - Germ cell testicular tumors in clinical stage A and normal values of serum tumor mark-ers post-orchiectomy: the experience in the management of 300 consecutive patients. AB - PURPOSE: To report the outcome and survival of patients with clinical stage A (CS A) testicular seminoma (TS) treated with adjuvant carboplatin (CBDCA), and the value of primary nerve-sparing retroperitoneal lymphadenectomy (RPLA), adjuvant cisplatin and surveillance in the risk-adapted management of CS-A patients with nonseminomatous testicular tumors (NSTT) and normal values of serum tumor markers post-orchiectomy. PATIENTS AND METHODS: From August 1985 to June 2003, 300 patients with CS-A germ cell testicular tumors (GCTT) entered a prospective non randomized study. 163 patients with TS received post-orchiectomy 2 cycles of adjuvant CBDCA (400 mg/m(2) q 3 wks). 137 patients with NSTT were divided into two groups according to risk-adapted management: arm A (n=33)- RPLA in 23 high risk patients (pre-orchiectomy AFP > 80 ng/ml, > 80% embryonal carcinoma, microvascular tumor invasion/VI+), and in 10 low-risk patients; and arm B (n=104) 65 high-risk patients received 2 cycles of cisplatin-based chemotherapy, whereas 39 patients with low risk were put under surveillance. RESULTS: After a median follow-up of 4 years (range 1-9) all patients with TS were alive and disease-free (ADF). Relapses occurred in 3 (1.9%) patients treated with CBDCA, with complete response (CR) following cisplatin-based chemotherapy. Arm A relapses following RPLA in high-risk pathological stage (PS)- A occurred in 3 out of 18 (17%) patients, with CR following chemotherapy in 2 of them, while 5 patients with retroperitoneal lymph node (RPLN) metastasis had universal survival, resulting in 22 (95.6%) patients being ADF after a median follow-up of 9 years (range 8-10.2). Among 10 low-risk patients, 2 (20%) had RPLN metastasis and received cisplatin based chemotherapy without disease relapse. All 10 patients are ADF after a median follow-up of 8.8 years (range 6.7-10.4). In arm B one of 65 high-risk patients (1.5%) treated with cisplatin-based chemotherapy relapsed in the lung at 9 months. Sixty-four (98.5%) patients are ADF after a median follow-up of 4 years (range 1.2-6.5). Six of 39 patients (15.4%) on surveillance relapsed and achieved CR with subsequent chemotherapy alone. All of them are ADF after a median follow up of 5.5 years (range 1-10.2). CONCLUSION: Adjuvant CBDCA chemotherapy is an acceptable approach in CS-A TS, whereas 2 cycles of cisplatin-based chemotherapy compare well with the results taken with RPLA in high-risk CS-A NSTT. Surveillance is an appropriate strategy in strictly selected patients with low risk CS-A NSTT and normal post-orchiectomy values of serum tumor markers. PMID- 17343329 TI - Vinorelbine/VP-16 (etoposide) in metastatic breast cancer: a phase II study. AB - PURPOSE: This phase II study was conducted to evaluate the efficacy and tolerability of vinorelbine (navelbine) and oral VP-16 (etoposide) in pretreated metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Twenty-two female patients with therapy-resistant metastatic breast cancer were treated with vinorelbine 25 mg/m(2) i.v. on days 1 and 8 and oral VP-16 50 mg/m(2)/day for 14 days. Cycles were repeated every 28 days. Treatment was given until clear evidence of disease progression. RESULTS: Complete remission was observed in 3 (14%) patients, and partial remission or stable disease in 10 (45%) patients. Median duration of response was 4 months (range 2-8). Symptomatic improvement, irrespective of imaging methods results, as evaluated through improved performance status (PS), the lack of requirement for urgent palliative radiotherapy, and a decrease in steroids and analgesics doses was demonstrated in 10 (45%) patients through a special questionnaire completed by all patients. Side effects were manageable. Dose modification due to leucopenic fever were necessary in only 3 patients. Previous radiation therapy did not mitigate the application of full doses of chemotherapy. CONCLUSION: Vinorelbine/VP-16 combination is active and tolerable in relapsed and heavily pretreated MBC patients. PMID- 17343330 TI - 5-fluorouracil cardiotoxicity is a rare, dose and schedule-dependent adverse event: a prospective study. AB - PURPOSE: Cardiotoxicity associated with 5-fluorouracil (5FU) administration is infrequently reported in the literature, albeit case reports of acute coronary syndromes have been published. In the present study, patients undergoing 5FU chemotherapy were tested for the development of cardiac-related symptoms during its administration. PATIENTS AND METHODS: Five hundred twenty-two patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion were subjected to electrocardiogram (ECG) and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion was interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >2-fold enzyme elevation were admitted into a coronary care unit for at least 72 hours. Cases with acute myocardial infarction had to discontinue 5FU treatment. RESULTS: Overall 20 (3.8%) patients developed symptoms and/or ECG abnormalities due to 5FU. Patients with continuous 5FU infusion had a trend for higher incidence of cardiotoxicity (13/205, 6.3%) than the remaining (7/317, 2.2%; p=0.067). More specifically, increased toxicity was encountered in patients with continuous 24 h 5FU+ leucovorin (LV) infusion for 5 days compared to patients with the same schedule without LV (p <0.027) and patients with short 5FU+LV administration as well (p=0.024). Seven out of the 20 patients suffered acute myocardial infarction, 6 developed only ischemia, while ECG findings consistent with coronary vasospasm were detected in 4 patients and conduction disturbances in 3 patients (one subsequently died). CONCLUSION: The present study indicates a toxic effect of 5FU on myocardium, which is largely schedule dependent. High level of alert is required when using this drug, while its toxic effect on the coronary endothelium and myocardium merits further investigation. PMID- 17343331 TI - The results of concomitant and sequential chemoradiotherapy with cisplatin and etoposide in patients with locally advanced non-small cell lung cancer. AB - PURPOSE: To report on the treatment results and demographic characteristics of patients with locally advanced non small cell lung carcinoma (NSCLC) who were treated with concomitant or sequential chemoradiotherapy. PATIENTS AND METHODS: 132 patients with locally advanced NSCLC (stage IIIB) were evaluated. Their median age was 60 years (range 33-80). Histopathological diagnosis was epidermoid carcinoma in 96 (73%) patients, adenocarcinoma in 33 (25%) patients and large cell carcinoma in 3 (2%) patients. Karnofsky performance status (KPS) score was >/= 70 in 112 (85%) patients. Weight loss was greater than 5% in 34 (26%) patients at presentation. One hundred and six (80%) patients were treated with sequential chemoradiotherapy which consisted of 3 monthly cycles of cisplatin (100 mg/m(2), day 1) and etoposide (100 mg/m(2)/day, days 1-3) before radiotherapy. Radiotherapy consisted of a total dose of 60 Gy in 30 fractions (2 Gy / fraction), given to a volume including primary tumor and mediastinum. Two to 4 cycles of chemotherapy were administered after completion of radiotherapy to patients whose disease had not progressed after initial chemotherapy. Twenty-six patients were treated with concomitant chemoradiotherapy. The same radiotherapy regimen was started with the 2nd cycle of chemotherapy which consisted of cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2)/day, days 1-3). Chemotherapy was completed after 4 cycles in all patients. RESULTS: Overall survival (OS) was 14.5 months in 106 patients treated with sequential chemoradiotherapy and 14.6 months in 26 patients treated with concomitant chemoradiotherapy (p=0.99). Median time to progression was 9.77 months in the concomitant group and 11.6 months in the sequential group (p=0.47). However, progression-free survival was better in patients of both groups whose KPS was >70 (12.4 months versus 11.5 months, p= 0.02). While presence of anemia was found as an adverse prognostic factor only in univariate analysis, non-epidermoid histology, KPS less than 70 and presence of N2-N3 disease were found as adverse prognostic factors in both univariate and multivariate analysis. CONCLUSION: The addition of chemotherapy to radiation concomitantly or sequentially prolongs survival in locally advanced NSCLC patients with acceptable adverse event profiles in both arms compared with results of the trials in the literature in which radiotherapy is used as single treatment modality. PMID- 17343332 TI - Prostate brachytherapy: a three-year experience from the first 116 patients in Greece. AB - PURPOSE: To present the results from the first 116 patients with localized prostate cancer treated with transperineal ultrasonography-guided permanent brachytherapy, with special emphasis on the complications of this method. PATIENTS AND METHODS: During the last 3 years, 116 patients with localized prostate cancer underwent transperineal ultrasonography-guided permanent implantation with I(125) seeds. Permanent implantation consisted of 21-82 I(125) seeds of 0.529 mCi each, for a total implant dose of 145 Gy. The peripheral loading implant was used and a-blockers preimplantation were administered to most of our patients.The follow-up consisted of clinical examination and serum prostate specific antigen (PSA) estimation every 3 months. Three successive rises of PSA with a 3-month interval inbetween constituted a biochemical failure. RESULTS: No patient was incontinent after treatment. Acute urinary retention was developed in 9 (7.7%) patients. During the first 3 months postimplantation approximately 55% of the patients complained of dysuria, urgency, frequency and nocturia, but their urinary complaints disappeared within one year postimplantion. Three (2.5%) patients developed mild proctitis. Sixty-seven percent of the potent patients remained potent at the end of the first year. Biochemical relapse appeared in 5 (4%) of the 116 patients studied. CONCLUSION: It seems that prostate brachytherapy, a method that is well tolerated and safely administered, can be accomplished with minimal acute and chronic complications. Prostate size is a predictor for acute urinary retention and prophylactic use of a-blockers seems to reduce the incidence of postimplantion acute retention. Also, lower incidence of impotence was found in comparison with the incidence after radical prostatectomy. PMID- 17343333 TI - Microsurgical spinothalamic chordotomy in the treatment of cancer pain. AB - PURPOSE: Advances in cancer treatment continue to lengthen survival among cancer patients. As patients live longer, the need for effective pain control has gained increased importance for improving quality of life. In patients who do not respond to all available conservative methods of therapy for cancer pain, surgical methods have been applied; one of them is the open high thoracic spinothalamic chordotomy. PATIENTS AND METHODS: We present a group of 86 patients suffering from nociceptive cancer pain, caused by compression of lumbosacral plexus. All patients were treated by microsurgical open high thoracic spinothalamic chordotomy. These patients did not respond to any available conservative treatment. RESULTS: Immediately after surgery 68 (79%) patients had total pain relief. Of the remaining 18 (21%) patients, significant pain relief was achieved in 9 (10%), while in the remaining 9 patients this procedure had no effect. After a 6-month follow-up, total pain relief remained in 62 (72%) and significant pain relief in 10 (17%) of the patients. From 62 of patients with well-defined unilateral pain treated by "moderately deep" chordotomy, total pain relief was achieved in 53 (85%), lasting for 6 months in 49 (79%) of them. CONCLUSION: These results show that microsurgical chordotomy can achieve total control of intractable cancer pain in the majority (79%) of patients, especially in those with well-defined unilateral pain (85%), indicating the usefullness of this surgical approach in the treatment of nociceptive cancer pain. PMID- 17343334 TI - A preclinical survey on the efficacy of lactandrate in the treatment of colon carcinoma. AB - PURPOSE: There has been a recent and dramatic increase in the pace of drug development for colorectal cancer which holds promise to further improve curative therapy. We tested lactandrate, an alkylating ester of D-lactam androsterone, for antineoplastic activity against colon adenocarcinoma in vitro and in vivo. MATERIALS AND METHODS: The cytostatic and cytotoxic activity of lactandrate were evaluated in vitro against 9 human colon adenocarcinoma cell lines. The in vitro testing was performed with the sulforhodamine B (SRB) colorimetric assay and the mean concentrations of each drug that generated 50% (GI50) or total (100%) growth inhibition (TGI), as well as the drug concentrations that produced cytotoxicity against 50% of the cultured cells (IC50) were calculated. The in vivo antitumour effect was determined against two rodent colon carcinomas, the Colon 26 and the relatively chemoresistant Colon 38 carcinoma, as well as against the human xenograft CX-1 colon carcinoma. RESULTS: Lactandrate displayed a satisfactory activity against the 9 human colon cancer cell lines, inducing significant growth inhibition and cytotoxicity. Lactandrate induced antiproliferative activity against colon cancer cell lines linearly correlated with the carcinoembryonic antigen (CEA) production. There was a non-linear polynomial correlation between CEA production and the cytotoxic effect of lactandrate. The more differentiated cell lines DLD-1 and HCC2998 appeared more resistant to the cytostatic effect of lactandrate. In vivo, the compound produced a significant antitumour activity against Colon 26 and Colon 38, as well as a moderate antitumour effect against CX 1 colon carcinoma. CONCLUSION: Preclinical research supports the high in vitro and in vivo antitumour potential of lactandrate against colon carcinoma. Therefore, lactandrate represents an important candidate drug for further clinical development. PMID- 17343335 TI - Synergistic interaction between a novel mixed ligand copper(II) chelate complex and a panel of anticancer agents in T47D human breast cancer cells in vitro. AB - PURPOSE: We have developed a novel copper(II) chelate complex with a tridentate ONN-Schiff base ligand and the anion of salicylate, which presented a potent cytotoxic activity against a panel of human and murine cancer cell lines. In this experiment we explored the combined effect between Cu(SalNEt(2))salicylate (Cu Sal) complex and the widely used anticancer drugs carboplatin (CBDCA), cyclophosphamide (CTX) and paclitaxel (TXL) against T47D human breast cancer cells. Theoretical (quantum-chemical) study of this complex and its adducts with biological molecules were carried out, aiming at the elucidation of the underlying mechanism of action. MATERIALS AND METHODS: Cells grown in adherence in 96-well microplates were exposed simultaneously to both agents for 48 h. Drug cytotoxicity was assessed via the XTT colorimetric assay. The combined drug interaction was assessed with the median-effect analysis and the combination index (CI). RESULTS: Copper(II) salicylate complex was proved active against T47D human breast cancer cells. Concurrent treatment of cells with Cu-Sal complex and the chemotherapeutic drugs CBDCA, CTX and TXL, mainly showed a synergistic interaction in most concentration ratios. CONCLUSION: Cu-Sal complex interacts synergistically with tested chemotherapeutic drugs for most schedules of administration, and only occasionally an additive or antagonistic effect was apparent. With the aid of quantum-chemical calculations it was demonstrated that the mechanism of action of this complex involves binding to DNA and RNA. These findings prompt to search for possible interaction of this complex with other cellular elements of fundamental importance in cell proliferation. PMID- 17343336 TI - Radioligand binding assay determination of epidermal growth factor receptor in ovarian tumours. AB - PURPOSE: To introduce a quantitative method for determination of epidermal growth factor receptor (EGFR) expression in tissue samples taken from normal ovaries, benign and malignant ovarian tumours, convenient for routine tests. MATERIALS AND METHODS: About 1g of tissue was taken intraoperatively from 136 patients; 105 of them had histologically verified ovarian tumours (64 malignant, 42 benign) and 30 had normal ovaries. The tissue was frozen, preserved and transported in liquid nitrogen (-196 degrees C). The level and frequency of EGFR expression were determined by radioligand method, utilizing (125)I-labeled epidermal growth factor (EGF) and recombinant human EGF. The results were obtained as fmol bound EGF per mg protein from the membrane fraction. All samples having expression >/=3 fmol/mg were considered as positive. RESULTS: The frequency of EGFR expression was 52% (70/136 patients), with a mean level of expression 45 +/-11 fmol/mg (range 0-1332). From the EGFR-positive patients with malignant ovarian tumours 21 (62%) had progressive disease (PD) while only 4 (13%) patients with negative EGFR had PD (p=0.001). The mean progression-free interval in the first group was 4 months, and in the second group it was 11 months (p=0.0028). CONCLUSION: The proposed quanitative radioligand binding assay is easy to perform, rapid and well reproducible, and we recommend it for routine clinical use. PMID- 17343337 TI - Sialylation and fucosylation of cancer-associated prostate specific antigen. AB - PURPOSE: To examine sialylation and fucosylation of prostate cancer-associated prostate-specific antigen (PCa PSA) from localized prostate cancer and from metastatic prostate cancer, as relevant indicators of tumour stage-dependent microheterogeneity of its oligosaccharide chain. MATERIALS AND METHODS: Sera and urine were collected from a group of consenting patients and used as source of the examined PSA. Lectin-affinity chromatography was performed on the columns with immobilized sialic acid-specific lectins Sambucus nigra agglutinin (SNA) and Maackia amurensis lectin (MAA), and fucose-specific lectins Aleuria aurantia agglutinin (AAA) and Ulex europaeus agglutinin (UEA). PSA elution from the corresponding columns was monitored by measuring immunoreactivity to free (f) PSA form. RESULTS: The results of lectin affinity chromatographies of PCa PSA indicated distinct and high microheterogeneity of its oligosaccharide chain in respect to the presence of glycoforms differing in the position and the type of linkage of sialic acid or fucose, as well as alterations related to the examined PSA source (localized or metastatic prostate cancer). CONCLUSION: The observed decrease in SNA reactivity to metastatic PCa PSA in comparison with PCa PSA from localized prostate cancer may be of interest in the monitoring of response to therapy and scoring of its metastatic potential. PMID- 17343338 TI - Cytological grading of breast carcinoma with histological correlation. AB - PURPOSE: A grading system based on cytology would be helpful in the selection of patients for appropriate therapy. The aim of this study was to devise such a system for grading breast carcinoma based on cytological features alone. MATERIALS AND METHODS: Diagnostic fine needle aspiration (FNA) smears taken from 100 patients with invasive breast carcinoma were studied without knowledge of the subsequent grade and type of the tumors. The technique of aspiration employed a 10 ml syringe and 23 gauge needle. The aspirates were spread onto slides and half of the smears were rapidly air-dried and stained by May-Grunwald-Giemsa, while the rest were alcohol-fixed and stained by Papanicolaou technique. The features assessed were: nuclear pleomorphism, nucleoli, mitoses, nuclear/cytoplasmic ratio, apoptosis, necrosis, cell clustering, cel-lularity and tubular formation. Cytological features were compared to the histological grade of breast carcinomas following excision, and the results were analyzed by the x(2) test (the significance level was set to p<0.05), as well as by the correlation coefficients (ri). Multivariate analysis was carried out by multiple correlation coefficients (Rij) for each pair of significant parameters. RESULTS: Significant association between worsening cytological features and increasing histological grade were found with nuclear pleomorphism, nucleoli, mitoses, apoptosis, cellularity and tubular formation. A scoring system based on these 6 parameters enabled the classification of tumors into low and high cytological grades which showed a close correlation with histological grade with 81% concordance. The best multiple correlations were found for the following pairs of cytological parameters: mitoses-apoptosis (0.603), mitoses-tubular formation (0.572), apoptosis-nuclear pleomorphism (0.550) and mitoses-nuclear pleomorphism (0.545). CONCLUSION: On the basis of this study we conclude that the proposed system of grading breast carcinoma is possible from FNA cytology and it shows a good correlation with histological grade. PMID- 17343339 TI - Oxidative stress in blood in cases of untreated refractory anaemia. AB - PURPOSE: To examine some features of free radical processes in the blood of patients with untreated refractory anaemia (RA) and to interpret their pathogenetic role. MATERIALS AND METHODS: Products of the lipid peroxidation (malondialdehyde-MDA) in whole blood, some antioxidant systems - superoxide dismutase (SOD) in erythrocytes, catalase (CTS) activity and the concentration of sulfhydryl groups (SHG) in whole blood, as well as the spontaneous and stimulated chemiluminescent activity of polymorphonuclear leucocytes (PMNL), reflecting the production of oxygen free radicals, were studied in the blood of 21 patients suffering from untreated RA (study group) and in 45 healthy individuals (control group). RESULTS: Increased content of MDA (p<0.001), lowered level of CTS activity (p<0.001) and concentration of SHG (p<0.05), increased SOD activity (p<0.05) and an increase in the spontaneous PMNL oxidative activity (p<0.05) were found in the study group compared with the control group. CONCLUSION: Strong oxidative stress was recorded in the blood of patients with untreated RA. An assumption was made that the initial iron overload helps the initiation of free radical oxidative processes in blood, accompanied with spontaneous activation of PMNL. Erythrocyte membranes probably are the main target for oxidative attack. PMID- 17343340 TI - Lymphocyte subsets in peripheral blood as prognostic factors in colorectal cancer. AB - PURPOSE: To evaluate changes in different parameters of the immune status of colorectal cancer patients before their surgical treatment and to look for a possible impact these parameters could exert on overall survival. PATIENTS AND METHODS: Forty patients with histologically confirmed colorectal cancer in stage II (n=22), III and IV (n=18) were eligible for inclusion in the present study. Heparinized venous blood (5 ml) of patients was examined 5 days before surgery. Their preoperative white blood cell (WBC) count was >/=3.0*10(9)/l, hemoglobin >/=10 g/l, and platelets >/=180*10(9)/l. The indices of cellular immunity determined for all of the patients were the following: total leukocyte number, absolute number and percents of total lymphocytes, monocytes and neutrophils. The percentage and absolute number of lymphocytes subsets CD3(+), T-helpers (CD4(+)), T-cytotoxic cells (CD8(+)), immunoregulation index (CD4(+)/CD8(+)), B-lymphocytes (CD20(+)), natural killer (NK) cells (CD16(+)) were measured by immunofluorescence methods. RESULTS: Cox regression analysis showed no dependence of the survival on estimated cellular immunity parameters of colorectal cancer patients in stage II. However, the number of circulating lymphocytes and in particular of T cells and NK cells was an independent prognostic variable for overall survival of stage III and IV patients. Analyzing the dependence of survival on immunological indices of colorectal cancer patients, a significant dependence of survival was determined on the absolute preoperative number of total lymphocytes and lymphocyte subsets (total lymphocytes levels >/=1.2*10(9)/l, >/=CD3(+) >/=0.8*10(9)/l, CD4(+) >/=0.3* 10(9)/l, CD8(+) >/=0.3*10(9)/l, and CD16(+)>/=0.25*10(9)/l). Cox regression analysis showed that higher absolute number of lymphocyte subpopulations may be associated with longer survival of colorectal cancer patients in stage III and IV. CONCLUSION: This study suggests total number of lymphocytes >/=1.2*10(9)/l, CD3(+) >/=0.8*10(9)/l, CD4(+) >/=0.3* 10(9)/l, CD8(+) >/=0.3*10(9)/l, and CD16(+) >/=0.25*10(9)/l before surgery have a beneficial effect on overall survival of colorectal cancer patients in advanced stages (III and IV) of the disease. PMID- 17343341 TI - Diagnosis of prostate cancer in Serbia. AB - PURPOSE: A rising incidence of prostate cancer is noticed in USA and Europe, which might be due to better diagnostic procedures and screening programs started in some countries. We still lack epidemiological studies confirming the same trend in our country, but the rising number of patients in whom radical prostatectomy is performed is an indirect proof of bigger recruitment of patients with prostate cancer. The purpose of this study was to establish the most appropriate diagnostic protocol for detection of prostate cancer in our unscreened population. MATERIALS AND METHODS: Transrectal ultrasound (TRUS) guided biopsies of the prostate were performed in 229 patients. Biplanar transrectal probe with needle channel was used. Six to 10 tissue cores were obtained from each patient. RESULTS: The mean patients' age was 67.12 years (range 42-88). All patients had serum prostatic specific antigen (PSA) estimation before biopsy, which ranged from 0.41 to 1550 ng/ml (mean 50.83), with 146 (63.8%) patients having PSA level greater than 10 ng/ml. Free (F) PSA was performed in 120 (52.4%) patients; the range of F to total (T) PSA ratio was 0.02 to 0.74 (mean > 0.13). Digital rectal examination (DRE) was positive in 65% of the patients. The mean prostate volume was 40.5 ml (range 11-140). Cancer was diagnosed in 99 (43.2%) patients, prostate cancer in situ (PIN) alone was diagnosed in 37 (16.2%), chronic prostatitis in 73 (31.9%), while benign prostatic hyperplasia (BPH) was found in 20 (8.7%) patients. CONCLUSION: The cancer detection rate in our patients was high. In a lot of patients the biopsy was needed only for histological proof, not as a staging tool, the intention of which is the selection of patients with localized prostate cancer amenable to curative treatment. There is still reluctance to use PSA as a sole indication for biopsy, positive DRE still being mandatory. With such a policy we are missing a lot of curable prostate cancer cases, thus increasing the cost of treatment. A national policy including screening should be considered. PMID- 17343342 TI - Invasive micropapillary carcinoma of breast: case report with literature review. PMID- 17343343 TI - Acute abdomen as initial manifestation of M4 - acute non-lymphocytic leukemia. AB - Visceral involvement in acute non-lymphocytic leukemia (ANLL) seldom precedes hematological manifestation. We report on a patient with M4 - ANLL presenting with acute abdomen without any evidence of blood disorder. Laparotomy revealed only ileal wall oedema. Postoperative clinical deterioration led to a second-look operation combined with intraoperative endoscopy. Biopsied tissues were diffusely infiltrated by blasts characterised as HLA-DR (+), PGM1 (50% +), MPO (50% +) and CD 34 (-). Bone marrow reconfirmed these findings and showed positivity for CD4 (44%), CD11b (50%), CD11c (42%), CD13 (33%), CD34 (32%), and CD56 (54%). Chemotherapy achieved a complete but short remission. Relapse occurred 7 months later. Immediately after consolidation chemotherapy the profoundly immunosuppressed patient passed away after a lower respiratory tract infection. We discuss the contrast between histology and short disease duration, the unusual presentation and the bad prognosis, and attempt to correlate the clinical course with the coexpression of markers. PMID- 17343344 TI - Epidural metastasis of Ewing's sarcoma: a rare localisation. AB - Epidural spinal metastasis of Ewing's sarcoma is rarely observed. We report on a rare case of purely epidural spinal metastasis of Ewing's sarcoma with pain and paraplegia, and describe the treatment and final outcome of the patient. PMID- 17343345 TI - Anne of Austria (1601-1666), queen of France: died of breast cancer. AB - Anne of Austria ("the Spain's infant"), was married to Louis XIII, on October 25th, 1615. She became queen of France and they had two children: Louis (the future Louis XIV) and Philippe, duke of Orleans. Everybody knows that Anne of Austria died of breast cancer. This is a widely known fact, so we are not going to add anything but some details, which are generally ignored. PMID- 17343346 TI - Variation in organ volumes of matched BALB/c mice by microcomputed tomography analysis. AB - High-resolution microcomputed tomography technology has allowed researchers to use live mice to address questions that previously could be answered only at necropsy. Serial analyses of the same mouse allow tissue changes to be followed over time. The ability to follow a single mouse noninvasively can decrease the total number of mice required for the study. The magnitude of inter-mouse variation for matched mice undergoing microcomputed tomography has not been determined previously. We selected lung and contrast-enhanced stomach as tissues of standard size and anatomical structure that were hypothesized to vary minimally between mice. The analyses of the tissue volumes from matched mice showed considerable variation among mice, among multiple sequential scans of the same mouse, and even among multiple evaluations of the same scan. More variation occurred with repeated scans of the same mouse (intramouse variation) than between mice (intermouse variation). In addition, significant variation and obvious bias was detected between the 2 scan evaluators. These data suggest that to obtain the widest range of possible values, among which the true value would be found, multiple analyses of multiple scans of the same mouse must be performed by multiple scan evaluators. PMID- 17343347 TI - Effect of method of euthanasia on sperm motility of mature Sprague-Dawley rats. AB - Euthanasia is one of the most commonly performed procedures in laboratory animal settings. The method of euthanasia may affect experimental results in studies using animals and must be compatible with research objectives including subsequent tissue analyses. Our present study was performed to evaluate the effects of 7 euthanasia methods on sperm motility in mature rats. Rats were euthanized using CO2, 2 commercially available euthanasia solutions (Beuthanasia D and Sleepaway), and 4 volatile anesthetics (enflurane, halothane, isoflurane, and sevoflurane). Rats euthanized by rapid decapitation alone served as negative controls, and a-chlorohydrin-treated rats euthanized by rapid decapitation were positive controls for sperm impairment. For 5 of these methods, we also measured time to ataxia, recumbency, respiratory arrest, and no auscultable heartbeat. Immediately after euthanasia of each rat, distal caudal epididymides were removed; 1 was processed for automated sperm motility analysis, and the other was frozen for subsequent concentration analysis. Time to all measured parameters was less for volatile anesthetics than for Beuthanasia-D. Times to last respiration and no heartbeat were less for halothane and isoflurane than for enflurane and sevoflurane. Percentage motile sperm did not differ significantly between methods. Percentage progressively motile sperm did not vary significantly between methods except for Beuthanasia-D, for which it was significantly less than the negative control value. Specific sperm motion parameters for each euthanasia method except CO2 and Sleepaway varied significantly from the negative control. Our results indicate that the method of euthanasia is an important consideration when rat sperm motility parameters must be evaluated. PMID- 17343348 TI - Discrimination of C57BL/6J Rj and 129S2/SvPasCrl inbred mouse strains by use of simple sequence length polymorphisms. AB - We present a list of simple sequence length polymorphisms (SSLPs) that was used in a polymerase chain reaction (PCR)-based marker-assisted selection protocol to facilitate the generation of a C57BL/6J Rj congenic strain from a mixed 129S2/SvPasCrlxC57BL/6J Rj background. We chose informative SSLP markers that would permit evaluation of the PCR products on NuSieve agarose or nondenaturing polyacrylamide gels. This list of oligonucleotide pairs is useful for analyzing and backcrossing knockout or transgenic strains derived from 129S2/SvPasCrl or C57BL/6J Rj backgrounds. PMID- 17343349 TI - Genomic comparison of Lewis and Wistar-Furth rat substrains by use of microsatellite markers. AB - Inbred strains of the laboratory rat (Rattus norvegicus) are commonly used models in biomedical and behavioral research. Genetic contamination caused by breeding errors, incomplete inbreeding with residual allogenicity, mutation, and genetic drift all are known to contribute to substrain divergence. Therefore, colonies of inbred strains from various suppliers likely contain differing amounts of genetic variation. We used microsatellite markers to scan the genomes and compare the genetic composition of 3 Lewis substrains and 2 Wistar-Furth substrains obtained from 3 different suppliers. LEW/SsNHsd rats showed approximately 37% genomic difference as compared with LEW/MolTac rats, and 8% difference as compared with LEW/Crl rats. WF/NHsd rats demonstrated a difference of approximately 8% as compared with WF/CrCrl rats. Investigators should consider the background genetics of the particular strains for their research projects and should use strains from a single source when feasible. PMID- 17343350 TI - Anesthesia for cardiovascular interventions and magnetic resonance imaging in pigs. AB - Large animal models are still required for many experimental purposes. The aim of the current study was to define a viable narcotic procedure for experimental cardiovascular interventions and imaging in pigs. A total of 32 domestic pigs were used. Animals received propofol, midazolam, and fentanyl as continuous intravenous infusion anesthesia for complex vascular interventions, angiographic X-ray imaging, and magnetic resonance imaging (MRI). Anesthesia was maintained for 6 to 10 h. The initial hourly doses were 2.29 mg/kg of propofol, 1.14 mg/kg of midazolam, and 0.009 mg/kg of fentanyl, with controlled ventilation. Anesthesia, interventions, imaging, periods of apnea of as long as 2 min, and transportation were well-tolerated. Stress-induced arrhythmias were not noted, and artifact-free imaging was achieved. The combination of propofol, midazolam, and fentanyl is well-suited for experimental angiographic interventional studies, experimental cardiovascular MRI, and MR-guided interventions in pigs. PMID- 17343351 TI - Use of environmentally enriched housing for rats with spinal cord injury: the need for standardization. AB - A variety of rehabilitation methods that increase social interaction and locomotor activity are reported to yield positive benefits in humans and animals with spinal cord injury (SCI). Environmental enrichment often incorporates group housing, increased cage size, and objects to increase social interaction and stimulate locomotor activity of animals. Others have reported that adult rats housed in enriched environments immediately after moderate contusion thoracic SCI show improvements in locomotion, but not in neurotransmission through or anatomy at the SCI site. In the present study, in contrast to previous reports, environmental enrichment did not improve the locomotion of rats with contusion thoracic SCI. Furthermore, as in previous reports, improvements were not observed for either electrophysiologic measures of neurotransmission through (transcranial magnetic motor-evoked potentials) and caudal to (magnetic-evoked interlimb reflex) the injury site or the amount of spared white matter at the epicenter. Determining the effectiveness of environmental enrichment to improve locomotor recovery in the SCI model requires standardization of housing procedures, outcome measures, and analyses. PMID- 17343352 TI - Efficacy of fenbendazole and milbemycin oxime for treating baboons (Papio cynocephalus anubis) infected with Trichuris trichiura. AB - We evaluated the efficacy of fenbendazole (FBZ) and milbemycin oxime (MO) in the treatment of baboons (Papio cynocephalus anubis) with naturally acquired Trichuris trichiura infection by comparing fecal egg count reduction (FECR) tests. We assigned 7 baboons, each singly housed and confirmed infected with T. trichiura, to treatment groups of FBZ (n=3) or MO (n=3), or as a control (n=1). All (100%) baboons that received FBZ stopped shedding T. trichiura eggs within 6 d of treatment, and fecal egg counts remained negative at 65 d after treatment. Although the number of T. trichiura eggs shed per gram of feces from 2 (67%) baboons decreased significantly after the second treatment with MO, this regimen never totally eliminated eggs of T. trichiura. The results of our study indicate that FBZ was more effective for treating baboons with T. trichiura than was MO. PMID- 17343353 TI - Strategies for refinement of abdominal device implantation in mice: strain, carboxymethylcellulose, thermal support, and atipamezole. AB - A widely used in vivo technique in mice and other species is the surgical implantation of transmitters for telemetric monitoring of core body temperature, locomotor activity, and other variables. However, these devices are quite large relative to the size of the mouse abdomen. We report here on the results of several related studies that we conducted to evaluate refinement strategies relevant to implantation of abdominal devices in mice. First, we evaluated survival from surgery as a function of strain and body weight and found that both parameters influence the proportion of mice that survive. Second, we assessed the effect of several interventions on postsurgical recovery of food and water intakes, core temperature, and locomotor activity. Some of the interventions were associated with increased mortality (atipamezole) or were otherwise detrimental (the abdominal lubricant carboxymethylcellulose), whereas others had little or no effect on recovery (thermal support). These findings indicate that interventions presumed to promote recovery from surgery that are based on data from other species may not always have the anticipated positive effect in mice. This study therefore underscores the need to carefully assess the effect of modifications in experimental procedures to avoid causing unexpected complications in mice. PMID- 17343355 TI - Complete blood count, clinical chemistry, and serology profile by using a single tube of whole blood from mice. AB - Clinical pathology is a valuable means for assessing specific organ pathology and a screening tool for general animal health. Routine clinical pathology evaluation in mice usually includes whole blood for a complete blood count (CBC) and a clinical biochemistry analysis. Acquisition and analysis of these samples can be problematic due to the small volumes of blood that can be obtained from a mouse. Typically, a complete blood count requires blood from a tube containing an anticoagulant, whereas a clinical biochemistry profile needs blood from a serum clot tube. Because of the small volume that can be obtained, splitting the blood from a single mouse into 2 different tubes may result in inadequate samples to perform the desired tests or introduce inaccuracies. We explored the feasibility of using a single lithium heparin tube for generation of a CBC, biochemistry profile, and serology profile. We also evaluated the consistency of CBC data, including the quality of a peripheral blood smear taken from a lithium heparin or EDTA tube after various storage times. We found that CBC, biochemistry, and serology profiles could be obtained more readily when blood samples were placed in a single lithium heparin tube than in 2 separate tubes. In addition, the quality of blood smears and CBC results from the lithium heparin tube were comparable (with few exceptions) to those from an EDTA tube after prolonged storage. PMID- 17343354 TI - A specific polymerase chain reaction based on the gyrB gene sequence and subsequent restriction fragment length polymorphism analysis of Pasteurella pneumotropica isolates from laboratory mice. AB - For a molecular identification and typing tool, we developed a specific polymerase chain reaction (PCR) based on the gyrB gene sequence and a subsequent restriction fragment length polymorphism (RFLP) analysis using the products amplified from the specific PCR to facilitate discrimination of biotypes of Pasteurella pneumotropica from laboratory mice. Appropriate PCR products, a 1039 basepair fragment for biotype Jawetz and a 1033-basepair fragment for biotype Heyl, were amplified by use of the primers CZO-1 and NJO-2 from all 105 P. pneumotropica isolates tested and the 2 reference strains but not from other bacterial species tested. MspI digestion of PCR-generated products showed 3 RFLP patterns among the 105 isolates, and these patterns correlated with the biotype of the isolate (RFLP pattern 1, biotype Jawetz; RFLP pattern 2, biotype Heyl; and RFLP pattern 3, biotype Jawetz with Beta-hemolytic activity). Our procedure identifies and biotypes isolates of P. pneumotropica from laboratory mice, using simple PCR and enzymatic restriction techniques. Therefore, this procedure is useful as a rapid identification and biotyping tool for isolates of P. pneumotropica from laboratory mice. PMID- 17343356 TI - Automated mouse euthanasia in an individually ventilated caging system: system development and assessment. AB - We developed a CO2 euthanasia system that functions as an individually ventilated caging system and that accommodates the simultaneous euthanasia of as many as 70 cages of mice. The automated, logic-controlled system allows euthanasia of mice in their home cage, provides consistent and reproducible delivery of CO2, permits visualization of animals during euthanasia, and integrates various safety features. Requirements for the safe use of this system are that all cage locations are to be filled and that engineering controls (that is, a thimble connection) be used to minimize CO2 contamination of the immediate environment. The system was evaluated using mice that were nongravid and greater than 6 d of age. CO2 measurements were made over time to assess the reproducibility of intracage CO2 levels and the effect of 3 supply plenum pressures (0.35, 0.25, and 0.15 in. H2O) on maximal intracage CO2 concentration, CO2 fill slope, time until CO2 detection, and time until maximal CO2 concentration. Results indicate that both supply plenum pressure and cage position on the rack affect intracage CO2 concentrations. We also conducted behavioral assessments of mice undergoing euthanasia to evaluate distress during euthanasia at 2 plenum pressures (0.15 and 0.35 in. H2O). Personnel experienced with laboratory mice did not discern differences in mouse distress associated with either cage location or plenum pressure. This system was safe, effective, and labor-saving for euthanizing large numbers of mice in an aesthetically acceptable and humane manner compatible with recommendations provided in the ACLAM 2005 Report on Euthanasia. PMID- 17343357 TI - Comparison of cardiovascular effects of tiletamine-zolazepam, pentobarbital, and ketamine-xylazine in male rats. AB - We allocated 35 male Sprague-Dawley rats into 7 groups and anesthetized each by using one of the following regimens: ketamine 50 mg+xylaxine 5 mg; ketamine 75 mg+xylazine 5 mg; pentobarbital 45 mg; and Telazol 30, 40, 50, and 60 mg/kg; supplemental doses were used as required. Respiratory rate, heart rate, mean arterial pressure, cardiac index, and stroke index were measured every 30 min for 4 h. The Telazol groups showed a dose-dependent increase in duration of anesthesia. Duration of anesthesia was significantly shorter for the ketamine and pentobarbital groups than for any of the Telazol doses. Heart rate showed a dose dependent decrease among the Telazol groups, but overall heart rate in these groups was higher than in the ketamine and pentobarbital groups. Mean arterial pressure in the Telazol 40 and 50 groups was significantly higher than the pentobarbital and higher ketamine groups yet lower than that of the Telazol 60 group. Overall animals anesthetized with Telazol showed the highest cardiac index, ketamine intermediate, and pentobarbital the lowest; cardiac index was higher in the Telazol 50 group than in either the Telazol 30 or pentobarbital groups. The pentobarbital group exhibited the lowest stroke index, whereas ketamine-treated animals had an intermediate stroke index. These differing effects of anesthetics on cardiovascular parameters must be considered when choosing an anesthesia regimen or comparing data from different studies. In our model, the Telazol 40 and 50 groups appeared to exhibit the fewest adverse cardiovascular effects. PMID- 17343358 TI - The evaluation of whole-body plethysmography as a semiautomated method for analysis of emesis in the house musk shrew (Suncus murinus). AB - We analyzed the cisplatin-induced emetic responses of Suncus murinus by observation of both videorecorded behavior and changes in peak expiratory flow (PEF) as monitored by whole-body plethysmography. Analysis of the PEF data by use of a macro program revealed emesis-related changes in PEF. Cisplatin dose response curves obtained by both methods showed similar emesis profiles. In addition, our PEF-based analytical method could be used to assess emesis changes induced by various other emetogens (veratrine hydrochloride, nicotine bitartrate, and copper sulfate) and confirmed the efficacy of the antiemetic drugs ondansetron, metoclopramide, and GR205171 in the cisplatin-induced emesis model. These results demonstrate that the use of whole-body plethysmography to follow changes in PEF was an effective semiautomated method of assessing emetic responses in Suncus murinus. This novel semiautomated method may provide an objective, sensitive, and efficient way to study emesis in animal models. PMID- 17343359 TI - Epistylididae ectoparasites in a colony of African clawed frogs (Xenopus laevis). AB - This report describes the discovery and treatment of a multiagent infection in a captive colony of adult, female Xenopus laevis. Animals were determined to be infected with Saprolegnia sp, a relatively common fungal parasite in laboratory housed frogs, and a less common ectoparasite, Epistylis sp, that had been described only once before in frogs. We discuss the diagnosis, pathology, and treatment of Epistylis and the importance of water-quality monitoring and husbandry in the care of these research animals. PMID- 17343360 TI - Uterine epithelioid trophoblastic tumor in an African green monkey (Chlorocebus aethiops sabaeus). AB - A uterine mass was detected on physical exam in a multiparous African green monkey as an incidental finding, and the well-circumscribed mass was removed via hysterectomy. Histologically, the mass consisted of sheets, nests, and cords of uniform intermediate trophoblastic cells with eosinophilic or clear cytoplasm. These neoplastic cells aggregated around blood vessels, forming islands of viable tumor cells amid extensive areas of coagulative necrosis with calcification in a 'geographic' pattern of necrosis. Immunohistochemistry of the trophoblastic cells revealed strong and diffuse staining for pancytokeratin AE1/3 and p63, with weak and moderate staining for human placental lactogen and placental alkaline phosphatase, respectively. Immunohistochemical staining for smooth muscle actin, epithelial membrane antigen, and human chorionic gonadotropin was negative. Overall, the histologic and immunohistochemical features of this tumor were consistent with those of epithelioid trophoblastic tumor. This rare tumor type has not been reported previously to occur in African green monkeys. PMID- 17343361 TI - Preparation of homogeneous dispersions of tunicate cellulose whiskers in organic solvents. PMID- 17343362 TI - Analytical developments for high-precision measurements of W isotopes in iron meteorites. AB - A procedure was developed to accurately measure the W isotopic compositions of iron meteorites with a precision of better than +/-0.1 epsilon on epsilon182W and epsilon184W (normalized to 186W/183W). Purification of W was achieved through a two-step, ion-exchange procedure. In most cases, the yield is better than 80%, and purified W solutions are clear of matrix elements and direct isobars of W. The final W solutions were analyzed using a Micromass Isoprobe multicollector inductively coupled plasma mass spectrometer (MC-ICPMS). Tests performed on mixtures of terrestrial standards and meteorite samples demonstrate that the method is accurate and that epsilon182W variations as small as approximately 0.1 epsilon can be detected. Analyses of three different aliquots of the Gibeon (IVA) iron meteorite obtained over a period of 6 months show identical epsilon182W values with a weighted mean of 3.38 +/- 0.05, consistent with literature data for IVA iron meteorites, and indicating that the metal-silicate differentiation event in its parent body was either contemporaneous with or slightly postdated (by up to approximately 2.5 My) the formation of refractory inclusions. We demonstrate our ability to measure epsilon184W accurately and precisely (within +/-0.1 epsilon), which is useful for characterizing cosmogenic and nucleosynthetic effects that may be present in iron meteorites. We also report for the first time measurements of epsilon180W, albeit with large error bars (<+/-4 epsilon, in most cases). PMID- 17343363 TI - Optimized threshold selection for single-molecule two-color fluorescence coincidence spectroscopy. AB - Two-color coincidence detection is a single-molecule fluorescence technique that is capable of resolving subpopulations of biomolecular complexes at very low concentrations. In this paper, we have developed a method that automatically determines appropriate thresholds for the analysis of sets of two-color coincidence data. This has the distinct advantage of allowing the rapid determination of optimized thresholds in a reproducible fashion. The trade-offs involved in such selections are that the thresholds should be high enough both to exceed the background photon count rates and to ensure a low rate of chance coincident events and that they should be low enough to give reasonably high rates of fluorescence events. Previously, thresholds were selected by judgment to balance these various separate considerations. The method reported in this paper incorporates the three factors into the maximization of a single value derived from the data as a function of the thresholds used in the two channels. The value that is maximized is a ratio of event rates, specifically the rate of coincident events above that expected by chance, divided by the total event rate; this is called the association quotient. In this paper, we demonstrate that maximization of the association quotient selects appropriate thresholds for data derived from dual-labeled duplex DNA samples over a range of concentrations and laser powers. This method should allow the application of two-color coincidence detection to more complex biological systems and cells where the sample concentration and background levels are more variable and where it is not possible to run separate control experiments to determine the latter statistics. PMID- 17343364 TI - Chemometric study of Maya Blue from the voltammetry of microparticles approach. AB - The use of the voltammetry of microparticles at paraffin-impregnated graphite electrodes allows for the characterization of different types of Maya Blue (MB) used in wall paintings from different archaeological sites of Campeche and YucatAn (Mexico). Using voltammetric signals for electron-transfer processes involving palygorskite-associated indigo and quinone functionalities generated by scratching the graphite surface, voltammograms provide information on the composition and texture of MB samples. Application of hierarchical cluster analysis and other chemometric methods allows us to characterize samples from different archaeological sites and to distinguish between samples proceeding from different chronological periods. Comparison between microscopic, spectroscopic, and electrochemical examination of genuine MB samples and synthetic specimens indicated that the preparation procedure of the pigment evolved in time via successive steps anticipating modern synthetic procedures, namely, hybrid organic inorganic synthesis, temperature control of chemical reactivity, and template like synthesis. PMID- 17343365 TI - Identification of oxidation products of squalene in solution and in latent fingerprints by ESI-MS and LC/APCI-MS. AB - An investigation was carried out to identify oxidation products of squalene (SQ) in latent fingerprints. Oxidation products of SQ incubated in solution with Rose Bengal as a photooxidizer were isolated by semipreparative HPLC-UV and identified by direct infusion ESI-MS and flow injection APCI-MS. Squalene hydroperoxides ranging from squalene monohydroperoxide (SQ-[OOH]) to SQ-[OOH]5 were identified together with SQ epoxide. SQ-[OOH] was the main oxidation product. An LC/APCI-MS method was developed and used to monitor the fate of SQ in solution and in latent fingerprints and the formation of SQ-[OOH] and SQ epoxide. SQ-[OOH] and SQ epoxide were detected in freshly deposited prints but increased markedly after 1 day and continued to increase up to 5 days after print deposition. By day 7, these substances could no longer be detected in prints. SQ was rapidly depleted from prints such that by day 7 it was no longer detected. A similar pattern was seen for SQ stored in the light in dichloromethane but with a slower formation of SQ-[OOH] and SQ epoxide. The oxidation of SQ in solution in the presence and absence of photooxidizer was shown by TLC to proceed as follows: SQ-->SQ-[OOH]+SQ epoxide. SQ-[OOH]-->SQ-[OOH]2-->SQ-[OOH]3-->SQ-[OOH]4+SQ-[OOH]5, with oxidation being more rapid in the presence of photooxidizer. SQ-[OOH]4 and SQ-[OOH]5 could still be detected at 20 days in a solution of SQ aged in solution in the absence of photooxidizer. The oxidation products of SQ should make suitable targets for development of new reagents for visualizing latent fingerprints in forensic science. PMID- 17343366 TI - Shape-selective extraction of PCBs and dioxins from fish and fish oil using in cell carbon fractionation pressurized liquid extraction. AB - This paper describes a new shape-selective, pressurized liquid extraction (PLE) procedure for extracting polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and PCBs from food and feed samples with an integrated carbon fractionation step. Initially this was done using specially designed inserts for 34-mL cells, but subsequently, large solid cells (66 mL) were machined to increase the capacity and robustness of the system. Depending on the carbon load and extraction solvent strength, the non-ortho PCBs were recovered either with the bulk of the PCBs or with the PCDD/Fs. The former is preferable if PCDD/Fs are the targets. In most cases, however, data are required for all indicator PCBs, WHO-PCBs, and PCDD/Fs. Therefore, further efforts focused on developing, optimizing, and validating a cost- and time-efficient PLE procedure that can extract these targets, separate non-ortho PCBs and PCDD/Fs from the bulk of the PCBs, allow gravimetric fat determinations, and requires a minimum of postextraction cleanup. The performance of the resulting procedure was assessed in experiments with a fish tissue reference material. The trueness of the WHO-PCB TEQ, PCDD/F-TEQ, and total-TEQ data were -8, -5, and -7%, respectively, and the corresponding CVs were 1.5, 0.5, and 1.3%; within the limits set by the European community for gas chromatography-high-resolution mass spectrometry methods for food and feed control. PMID- 17343367 TI - In the presence of phospholipids, glycosaminoglycans potentiate factor Xa mediated protein C activation by modulating factor Xa activity. AB - Although the thrombin/thrombomodulin complex is considered the physiological activator of protein C, factor Xa (f.Xa) can also activate protein C in a reaction that is potentiated by glycosaminoglycans. To explore this phenomenon, we first examined the effect of glycosaminoglycans of varying degrees of sulfation on the kinetics of protein C activation by f.Xa in the presence of Ca2+ and phosphatidylcholine-phosphatidylserine vesicles (PCPS). Heparin increased the rate of protein C activation by f.Xa by 4-fold. In contrast, N-desulfated heparin had no effect on activation, whereas dextran sulfate, which is more sulfated than heparin, increased catalytic efficiency 21-fold. These data suggest that the capacity of glycosaminoglycans to catalyze protein C activation by f.Xa depends on their degree of sulfation. The affinities of individual glycosaminoglycans for protein C and f.Xa were measured in the absence or presence of PCPS by monitoring changes in extrinsic fluorescence when fluorescein-labeled f.Xa or protein C was titrated with the various glycosaminoglycans. Heparin binds protein C with low affinity in the absence or presence of PCPS. In contrast, the affinity of heparin for f.Xa is 86-fold higher in the presence of PCPS compared to that in the absence of PCPS. Similar results were obtained using surface plasmon resonance. These findings suggest that a high affinity glycosaminoglycan binding site is exposed when f.Xa binds to PCPS. The observation that heparin promotes f.Xa mediated activation of prethrombin 1 only in the presence of phospholipid suggests that glycosaminoglycan binding modulates the active site of f.Xa. This study reveals that when f.Xa interacts with anionic phospholipids, glycosaminoglycans bind f.Xa more tightly, allosterically modulate its active site, and enhance its capacity to activate protein C. PMID- 17343368 TI - Mechanism of calmodulin recognition of the binding domain of isoform 1b of the plasma membrane Ca(2+)-ATPase: kinetic pathway and effects of methionine oxidation. AB - Calmodulin (CaM) binds to a domain near the C-terminus of the plasma membrane Ca2+-ATPase (PMCA), causing the release of this domain and relief of its autoinhibitory function. We investigated the kinetics of dissociation and binding of Ca2+-CaM with a 28-residue peptide [C28W(1b)] corresponding to the CaM-binding domain of isoform 1b of PMCA. CaM was labeled with a fluorescent probe on either the N-terminal domain at residue 34 or the C-terminal domain at residue 110. Formation of complexes of CaM with C28W(1b) results in a decrease in the fluorescence yield of the fluorophore, allowing the kinetics of dissociation or binding to be detected. Using a maximum entropy method, we determined the minimum number and magnitudes of rate constants required to fit the data. Comparison of the fluorescence changes for CaM labeled on the C-terminal or N-terminal domain suggests sequential and ordered binding of the C-terminal and N-terminal domains of CaM with C28W(1b). For dissociation of C28W(1b) from CaM labeled on the N terminal domain, we observed three time constants, indicating the presence of two intermediate states in the dissociation pathway. However, for CaM labeled on the C-terminal domain, we observed only two time constants, suggesting that the fluorescence label on the C-terminal domain was not sensitive to one of the kinetic steps. The results were modeled by a kinetic mechanism in which an initial complex forms upon binding of the C-terminal domain of CaM to C28W(1b), followed by binding of the N-terminal domain, and then formation of a tight binding complex. Oxidation of methionine residues in CaM resulted in significant perturbations to the binding kinetics. The rate of formation of a tight binding complex was reduced, consistent with the poorer effectiveness of oxidized CaM in activating the Ca2+ pump. PMID- 17343369 TI - Ovarian cancer activity of cyclic amine and thiaether metal complexes. AB - A thiaether metal complex 1-aza-4,7-dithiacyclononane-RhCl3, 2, and cyclic amine metal complexes tacn-CuBr2, 3, and Me3tacn-RuCl3, 4, have been evaluated for anticancer activity against the ovarian cancer cell line NuTu-19 and for cell toxicity against the noncancerous ovarian tissue cell line OVepi. Specifically, metal complex 2 is active when compared to cisplatin at micromolar concentrations using the MTT and cell invasion assay. The in vitro results reported warrant further evaluation of metal complex 2 in living systems. PMID- 17343370 TI - Quinols as novel therapeutic agents. 7.1 Synthesis of antitumor 4-[1 (arylsulfonyl-1H-indol-2-yl)]-4-hydroxycyclohexa-2,5-dien-1-ones by Sonogashira reactions. AB - Interaction of 2-iodoaniline or 5-fluoro-2-iodoaniline with a range of arylsulfonyl chlorides affords sulfonamides that undergo Sonogashira couplings under thermal or microwave conditions with the alkyne 4-ethynyl-4 hydroxycyclohexa-2,5-dien-1-one followed by cyclization to 4-[1-(arylsulfonyl-1H indol-2-yl)]-4-hydroxycyclo-hexa-2,5-dien-1-ones. This method allows for incorporation of a range of substituents into the arylsulfonyl moiety, and compounds showed selective in vitro inhibition of cancer cell lines of colon and renal origin, a feature of compounds bearing the quinol pharmacophore. PMID- 17343371 TI - Identification and synthesis of a novel selective partial PPARdelta agonist with full efficacy on lipid metabolism in vitro and in vivo. AB - The aim was to identify a novel selective PPARdelta agonist with full efficacy on free fatty acid (FFA) oxidation in vitro and plasma lipid correction in vivo. Using the triple PPARalpha,gamma,delta agonist 1 as the structural starting point, we wanted to investigate the possibility of obtaining selective PPARdelta agonists by modifying only the acidic part of 1, while holding the lipophilic half of the molecule constant. The structure-activity relationship was guided by in vitro transactivation data using the human PPAR receptors, FFA oxidation efficacy performed in the rat muscle L6 cell line, and in vivo rat pharmacokinetic properties. Compound 7 ([4-[3,3-bis-(4-bromo-phenyl)-allylthio]-2 chloro-phenoxy]-acetic acid) was identified as a selective, partial agonist with good oral pharmacokinetic properties in rat. Chronic treatment of high fat fed ApoB100/CETP-Tgn mice with 7 corrected the plasma lipid parameters and improved insulin sensitivity. These data suggest that selective PPARdelta agonists have the potential to become a novel treatment of dyslipidemia. PMID- 17343372 TI - Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5 methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor. AB - In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge binding template for kinase inhibitors. By incorporating an N,N'-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model. In particular, compound 17p (ABT 869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models. PMID- 17343373 TI - Carbonic anhydrase inhibitors: inhibition of isozymes I, II, and IX with triazole linked O-glycosides of benzene sulfonamides. AB - We report the synthesis of a series of benzene sulfonamides containing triazole-O glycoside tails for evaluation as carbonic anhydrase (CA) inhibitors. These glycoconjugates were synthesized by the 1,3-dipolar cycloaddition reaction of 4 azidobenzenesulfonamide with O-propynyl glycosides. Compounds were assessed for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA I and II and the tumor-associated isozyme hCA IX (h = human). Against hCA I these compounds were either micromolar or low-nanomolar inhibitors, while against hCA II and IX inhibition in the range of 6.8-53 and 9.7-107 nM, respectively, was observed. The most potent inhibitor against hCA IX was the galactose derivative 8 (Ki = 9.7 nM); this is so far the most potent glycoconjugate inhibitor reported for the tumor-associated hCA IX. These carbohydrate-tethered sulfonamides may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly. PMID- 17343374 TI - Synthesis, structural characterization, and multifrequency electron paramagnetic resonance studies of mononuclear thiomolybdenyl complexes. AB - Reaction of Tp*MoVSCl2 with a variety of phenols and thiols in the presence of triethylamine produces mononuclear, thiomolybdenyl complexes Tp*MoVSX2 [Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate; X = 2-(ethylthio)phenolate (etp), 2-(n propyl)phenolate (pp), phenolate; X2 = benzene-1,2-dithiolate (bdt), 4 methylbenzene-1,2-dithiolate (tdt), benzene-1,2-diolate (cat)]. The complexes have been characterized by microanalysis, mass spectrometry, IR, EPR, and UV visible spectroscopic data, and X-ray crystallography (for the etp, pp, bdt, and cat derivatives). The mononuclear, six-coordinate, distorted-octahedral Mo centers are coordinated by terminal sulfido (MoS = 2.123(1)-2.1368(8) A), tridentate facial Tp*, and monodentate or bidentate O/S-donor ligands. Multifrequency (S-, X-, Q-band) EPR spectra of the complexes and selected molybdenyl analogues were acquired at 130 K and 295 K and yielded a spin Hamiltonian of Cs symmetry or lower, with gzz < gyy < gxx < ge and Az'z' > Ax'x' approximately Ay'y', and a noncoincidence angle in the range of beta = 24-39 degrees . Multifrequency EPR, especially at S-band, was found to be particularly valuable in the unambiguous assignment of the spin Hamiltonian parameters in these low-symmetry complexes. The weaker pi-donor terminal sulfido ligand yields a smaller SOMO-LUMO gap and reduced g-values for the thiomolybdenyl complexes compared with molybdenyl analogues, supporting existing crystallographic and EPR data for an apically coordinated oxo group in the active site of xanthine oxidase. PMID- 17343375 TI - Induced currents and electron counting in aromatic boron wheels: B8(2-) and B9-). AB - The newly discovered atom-centered polygonal wheels B8(2-) and B9- are predicted to show ring currents characteristic of aromatic systems. Ipsocentric mapping of induced current density for both molecules attributes a pi diatropic current to the four electrons of the doubly degenerate pi HOMO and a sigma diatropic current to the four electrons of the doubly degenerate sigma HOMO, each orbital pair having an available transition to corresponding LUMO orbitals in which the angular node count increases by one. Thus, on the magnetic criterion, B8(2-) and B9- are each both pi- and sigma-aromatic as a consequence of the nodal properties of the frontier orbitals of the pi- and sigma-stacks. PMID- 17343376 TI - Synthesis, crystal structure, and microstructure analysis of perovskite-type compounds LnCo0.95Ni0.05O3 (Ln = La, Pr, Nd, Sm, Gd, and Dy). AB - The crystal structure and the microstructure of LnCo0.95Ni0.05O3 compounds, synthesized by a soft chemistry process, were studied. Synchrotron and laboratory X-ray diffraction data of LnCo0.95Ni0.05O3 (Ln = Pr, Nd, Sm, Gd, and Dy) can be refined in the Pbnm space group (SG). The orthorhombic symmetry has been confirmed by transmission electron microscopy. The X-ray diffraction data of LaCo0.95Ni0.05O3 can be fitted with rhombohedral Rc and monoclinic I2/a SG. The comparison of experimental electron diffraction with theoretical simulation showed the monoclinic symmetry for the La compound has a better match than that of the rhombohedral symmetry. The Pr compound has shown to have a three dimensional microdomain texture in which the orientation of the real unit cell, i.e., approximately radical2ap x radical2ap x 2ap (where ap is the lattice parameter of the aristotype Pm3m perovskite, noted with a "p" subscript), alternates in each domain in one of the three space directions. PMID- 17343377 TI - Synthesis, structure, reactivity, and thermal isomerization of boron-substituted 13-vertex cobaltacarboranes (eta5-Cp)Co(eta6-R2C2B10Me8H2) (R = H, Et). AB - Reduction of boron-substituted carboranes o-R2C2B10Me8H2 (R = H, Et), thermal isomerization, and nucleophilic reaction of the resultant 13-vertex cobaltacarboranes were studied. Reaction of o-C2B10Me8H4 (1) with excess potassium metal in tetrahydrofuran (THF) gave, after recrystallization from a THF solution of 18-crown-6 ether, [[K(18-crown-6)(THF)2][K(18-crown-6)]][[4-(18-crown 6)-2,3,5,8,9,11,12,13-Me8-4,1,6-KC2B10H4]2] (2) in 78% yield. Interaction of 1 with excess sodium or potassium metal in THF, followed by treatment with CoCl2/CpNa and then aerobatic oxidation, afforded two boron-substituted 13-vertex cobaltacarboranes, 4-Cp-2,3,5,8,9,11,12,13-Me8-4,1,6-CoC2B10Me8H4 (3) and 4-Cp 2,3,5,9,10,11,12,13-Me8-4,1,6-CoC2B10Me8H4 (4), in 15% and 8% yield, respectively. Subsequently, thermal isomerization of 3 and 4 yielded another two new isomers, 4-Cp-2,3,5,6,8,11,12,13-Me8-4,1,9-CoC2B10Me8H4 (5) and 4-Cp 2,3,5,6,7,11,12,13-Me8-4,1,9-CoC2B10Me8H4 (6). Treatment of 3 or 4 with strong bases such as nBuLi and MeLi generated unexpected nucleophilic substitution products 4-nBuCp-2,3,5,8,9,11,12,13-Me8-4,1,6-CoC2B10Me8H4 (7), 4-nBuCp 2,3,5,9,10,11,12,13-Me8-4,1,6-CoC2B10Me8H4 (8a), and 4-MeCp-2,3,5,9,10,11,12,13 Me8-4,1,6-CoC2B10Me8H4 (8b) in good yields. Under the same reaction conditions, however, only one 13-vertex cobaltacarborane, 4-Cp-1,9-Et2-2,5,6,7,8,11,12,13-Me8 4,1,9-CoC2B10Me8H4 (10), was isolated when o-Et2C2B10Me8H2 (9) was used as the starting material. Complex 10 is a thermodynamically stable product and has a substitution pattern different from that of 3-6. These results show that the substituents on either the cage carbon or boron atoms have an important effect on the formation and thermal stability of the 13-vertex metallacarboranes. The formation of these complexes can be rationalized by the diamond-square-diamond mechanism. PMID- 17343378 TI - Dynamic docking of cytochrome b5 with myoglobin and alpha-hemoglobin: heme neutralization "squares" and the binding of electron-transfer-reactive configurations. AB - Intracomplex electron transfer (ET) occurs most often in intrinsically transient, low affinity complexes. As a result, the means by which adequate specificity and reactivity are obtained to support effective ET is still poorly understood. We report here on two such ET complexes: cytochrome b5 (cyt b5) in reaction with its physiological partners, myoglobin (Mb) and hemoglobin (Hb). These complexes obey the Dynamic Docking (DD) paradigm: a large ensemble of weakly bound protein protein configurations contribute to binding in the rapid-exchange limit, but only a few are ET-active. We report the ionic-strength dependence of the second order rate constant, k2, for photoinitiated ET from within all four combinations of heme-neutralized Zn deuteroporphyrin-substituted Mb/alphaHb undergoing ET with cyt b5, the four "corners" of a "heme-neutralization square". These experiments provide insights into the relative importance of both global and local electrostatic contributions to the binding of reactive configurations, which are too few to be observed directly. To interpret the variations of k2 arising from heme neutralization, we have developed a procedure by which comparisons of the ET rate constants for a heme-neutralization square permit us to decompose the free energy of reactive binding into individual local electrostatic contributions associated with interactions between (i) the propionates of the two hemes and (ii) the heme of each protein with the polypeptide of its partner. Most notably, we find the contribution from the repulsion between propionates of partner hemes to the reactive binding free energy to be surprisingly small, DeltaG(Hb) approximately +1 kcal/mol at ambient temperature, 18 mM ionic strength, and we speculate about possible causes of this observation. To confirm the fundamental assumption of these studies, that the structure of a heme-neutralized protein is unaltered either by substitution of Zn or by heme neutralization, we have obtained the X-ray structure of ZnMb prepared with the porphyrin dimethyl ester and find it to be nearly isostructural with the native protein. PMID- 17343379 TI - Synthesis, characterization, and photoinduced electron transfer in functionalized single wall carbon nanohorns. AB - Single-wall carbon nanohorns (SWNHs) are a new class of material that is closely related to single-wall carbon nanotubes. Here, we describe the synthesis and characterization of a series of SWNHs functionalized with ethylene glycol chains and porphyrins. Functionalization of carbon nanohorns has been achieved using two different synthetic protocols: (1) direct attack of a free amino group on the nanohorn sidewalls (nucleophilic addition) and (2) amidation reaction of the carboxylic functions in oxidized nanohorns. The nanohorn derivatives have been characterized by a combination of several techniques, and the electronic properties of the porphyrin/nanohorn assemblies (SWNH/H2P) have been investigated by electrochemistry, spectroelectrochemistry, and a series of steady-state and time-resolved spectroscopy. The cyclic voltammetry curve of nanohorn/porphyrin conjugate 6 showed a continuum of faradic and pseudocapacitive behavior, which is associated with multiple-electron transfers to and from the SWNHs. Superimposed on such a pseudocapacitive current, the curve also displays three discrete reduction peaks at -2.26, -2.57, and -2.84 V and an oxidation peak at 1.12 V (all attributed to the porphyrin moiety). Steady-state and time-resolved fluorescence demonstrated a quenching of the fluorescence of the porphyrin in SWNH/H2P conjugates 5 and 6 compared to the reference free base porphyrin. Transient absorption spectra permitted the electron-transfer process between the porphyrins and the carbon nanostructures to be highlighted. PMID- 17343380 TI - Photoinduced superparamagnetism in trimetallic coordination nanoparticles. PMID- 17343381 TI - A direct observation of a concerted two-bond breaking reaction. PMID- 17343382 TI - Nitric oxide-releasing fabrics and other acrylonitrile-based diazeniumdiolates. PMID- 17343383 TI - Supramolecular helical assembly of an achiral cyanine dye in an induced helical amphiphilic poly(phenylacetylene) interior in water. AB - A water-soluble amphiphilic poly(phenylacetylene) bearing the bulky aza-18-crown 6-ether pendants forms a one-handed helix induced by l- or d-amino acids and chiral amino alcohols through specific host-guest interactions in water. We now report that such an induced helical poly(phenylacetylene) with a controlled helix sense can selectively trap an achiral benzoxazole cyanine dye among various structurally similar cyanine dyes within its hydrophobic helical cavity inside the polymer in acidic water, resulting in the formation of supramolecular helical aggregates, which exhibit an induced circular dichroism (ICD) in the cyanine dye chromophore region. The supramolecular chirality induced in the cyanine aggregates could be further memorized when the template helical polymer lost its optical activity and further inverted into the opposite helicity. Thereafter, thermal racemization of the helical aggregates slowly took place. PMID- 17343384 TI - Saccharide-coated M12L24 molecular spheres that form aggregates by multi interaction with proteins. PMID- 17343386 TI - Directed catalytic asymmetric olefin metathesis. Selectivity control by enoate and ynoate groups in Ru-catalyzed asymmetric ring-opening/cross-metathesis. PMID- 17343387 TI - Lysine N(zeta)-decarboxylation in the BlaR1 protein from Staphylococcus aureus at the root of its function as an antibiotic sensor. PMID- 17343388 TI - A diosphenol-based strategy for the total synthesis of (-)-terpestacin. PMID- 17343391 TI - Enantioselective synthesis of C2 -symmetric spirobipyridine ligands through cationic Rh(I)/modified-BINAP- catalyzed double [2 + 2 + 2] cycloaddition. AB - [structure: see text]. Enantioenriched C2-symmetric spirobipyridine ligands were efficiently synthesized through a cationic rhodium(I)/(R)-Segphos or (R)-H8-BINAP complex-catalyzed enantioselective intramolecular double [2 + 2 + 2] cycloaddition of bis-diynenitriles. PMID- 17343390 TI - Model studies for heme oxygenase-catalyzed porphyrin meso hydroxylation. AB - [structure: see text]. Nonenzymatic model studies based on a porphyrin analogue (2,4-diacetyldeuteroporphyrin) that avoid the steric effect complications of the heme oxygenase active site were carried out to determine the polarity of the ferric hydroperoxide attacking species. Mass spectral and deuterium-labeling experiments indicate that the porphyrin meso positions that are at higher pi electron densities in ferric 2,4-diacetyldeuteroporphyrin are selectively attacked. This supports an electrophilic aromatic substitution mechanism for the heme oxygenase-catalyzed porphyrin meso hydroxylation. PMID- 17343392 TI - Ruthenium-catalyzed ring-closing metathesis to form tetrasubstituted olefins. AB - [structure: see text]. Increased efficiency for ring-closing metathesis to form tetrasubstituted olefins using N-heterocyclic carbene ligated ruthenium catalysts was achieved by reducing the size of the substituents at the ortho positions of the N-bound aryl rings. PMID- 17343393 TI - Hydrogen-bonded dimers of tetra-urea calix[4]arenes stable in THF. AB - [structure: see text]. Whereas tetra-urea derivatives of tetra-alkoxy calix[4]arenes 1 exist as single molecules in THF, dimeric hydrogen-bonded capsules are exclusively found for the corresponding calix[4]arene derivatives 3 and 2 with two or four free hydroxyl groups. Comparison with the rigidified tetra urea 5 suggests that this increased stability of the dimers is due to the stabilization of their four-fold symmetry by intramolecular hydrogen bonds between the phenolic hydroxyl groups. PMID- 17343395 TI - Novel polyclonal-monoclonal-based ELISA utilized to examine lupine (Lupinus species) content in food products. AB - Sweet lupines are increasingly used in food production. Cause for concern has been expressed due to the increase in reported lupine-induced allergic incidents and the association between lupine and peanut allergies. In the current study, a polyclonal-monoclonal antibody-based sandwich ELISA for the detection of lupine proteins in foods was developed. The assay was sensitive to both native and processed proteins from Lupinus angustifolius and Lupinus albus and had a detection limit of 1 mug/g. Intra- and interassay coefficients of variation were <5 and <17%, respectively. A selection of 112 food samples, both with and without lupine declaration, was evaluated for their content of lupine. The data showed that the majority were in agreement with the respective labeling. However, some inconsistency was seen, typically in bread/rolls and soy flours. PMID- 17343397 TI - Thermal phase behavior of DMPG: the exclusion of continuous network and dense aggregates. AB - 1,2-Dimyristoyl-sn-glycero-3-phospho-rac-glycerol has been suggested to form at intermediate temperatures and at high concentrations in low-salt solutions as a continuous sponge phase (Heimburg, T.; Biltonen, R. L. Biochemistry 1994, 33, 9477-9488). In the present study, the changes in signals seen for a range of fluorescent probes during phase transformations of this phospholipid indicate continuous melting and a change in lipid packing, in accordance with previous reports. However, in accordance with Lamy-Freund and Riske (Lamy-Freund, M. T.; Riske, K. A. Chem. Phys. Lipids 2003, 122, 19-32), no enhancement of lipid mixing within the putative sponge phase region was seen, suggesting a lack of a connected lipid surface. Accordingly, a typical sponge phase cannot account for the properties of the intermediate phase. The low scattering intensities of the latter have also been taken as evidence for disaggregation. While dynamic light scattering and data for membranes containing poly(ethylene glycol)-ylated lipids could lend credence to disaggregation, the most likely explanation for the scattering data would appear to be a shape transition without significant changes in neither vesicle aggregation nor bilayer connectivity. An abrupt change in light scattering and signals from some of the fluorescent probes used reveals a new transition at Tt approximately 43 degrees C, with the formation of a more ordered interface. PMID- 17343398 TI - Conjugated polyelectrolyte-grafted silica microspheres. AB - A direct method for preparation of conjugated polymer-grafted silica particles is reported. Silica particles (0.3 and 5 mum diameter) are treated with a 3 (trimethoxysilyl)propylamine derivative that is functionalized with an aryl iodide unit. A solution step-growth polymerization reaction is performed in solution that contains a dispersion of the aryl iodide-functionalized particles. The reaction is a Pd(0)-catalyzed (Sonogashira) A-B-type polymerization of an oligo(ethylene glycol)-fuctionalized diiodobenzene and a bis(propyloxy)sulfonate substituted diethynylbenzene. The overall process affords silica particles that feature a surface graft layer of an anionic poly(phenylene ethynylene)-type conjugated polyelectrolyte. The particle surface modification process was monitored by infrared (FTIR) spectroscopy, and the polymer-grafted silica particles were characterized by thermogravimetric analysis, scanning and transmission electron microscopy, confocal fluorescence microscopy, and absorption and fluorescence spectroscopy. The conjugated polyelectrolyte-grafted silica particles are highly fluorescent, and a Stern-Volmer quenching study of the particles' fluorescence with electron-transfer- and energy-transfer-type quenchers shows that the quenching response depends on the type of quenching mechanism. PMID- 17343399 TI - Photoredox chemistry of AOT: electron transfer and hydrogen abstraction in microemulsions involving the surfactant. AB - Time-resolved magnetic resonance experiments (TREPR and CIDNP) are used to investigate previously unobserved redox chemistry of the surfactant dioctyl sulfosuccinate ester (AOT) using the photoexcited triplet state of anthraquinone 2,6-disulfonate (3AQDS*). Several different free radicals resulting from two independent oxidation pathways (electron transfer and hydrogen abstraction) are observed. These include the radical ions of AQDS and sulfite from electron transfer processes, carbon-centered radicals from H-atom abstraction reactions, and an additional carbon-centered radical formed by electron transfer from the AOT sulfonate head group followed by the loss of SO3. The radicals exhibit intense chemically induced dynamic electron spin polarization (CIDEP) in their TREPR spectra. The intensity ratios of the observed TREPR signals for each radical depend on the water pool size and temperature, which in turn affect the predominant CIDEP mechanism. All signal carriers are accounted for by simulation, and CIDNP results provide strong supporting evidence for the assignments. PMID- 17343400 TI - Rigiflex, spontaneously wettable polymeric mold for forming reversibly bonded nanocapillaries. AB - We present a novel ultraviolet (UV)-curable mold that enables the formation of reversibly bonded nanocapillaries (500-50 nm) on a gold or silicon substrate. A sheet-type ( approximately 50 microm) polyethylene diacrylate (PEG-DA) mold was used for its rigiflex nature; it provides rigidity high enough for maintaining nanostructures (elastic modulus >70 MPa) and also flexibility good enough for intimate contact over a large area aided by weak electrostatic forces (zeta potential approximately -113.55 mW). The electrostatic charge is generated on a rigiflex PEG-DA mold upon peeling from an original engraved silicon master by mechanical friction, thereby assisting the formation of spontaneous contact with the gold or silicon substrate. PMID- 17343401 TI - Structure of mixed micelles formed in PEG-lipid/lipid dispersions. AB - Polyethylene glycol (PEG)-conjugated lipids are commonly employed for steric stabilization of liposomes. When added in high concentrations PEG-lipids induce formation of mixed micelles, and depending on the lipid composition of the sample, these may adapt either a discoidal or a long threadlike shape. The factors governing the type of micellar aggregate formed have so far not been investigated in detail. In this study we have systematically varied the lipid composition in lipid/PEG-lipid mixtures and characterized the aggregate structure by means of cryo-transmission electron microscopy (cryo-TEM). The effects caused by adding sterols, phosphatidylethanolamines, and phospholipids with saturated acyl chains to egg phosphatidylcholine/1,2-distearoyl-sn-glycero-3 phosphatidylethanolamine-N-[methoxy(polyethylene glycol)-2000 (EPC/DSPE-PEG2000) mixtures with a fixed amount (25 mol %) of DSPE-PEG2000 was studied. Further, the aggregate structure in 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine/1,2 dimyristoyl-sn-glycero-3-phosphatidylethanolamine-N-[methoxy(polyethylene glycol) 2000] (DMPC/DMPE-PEG2000) samples above and below the gel to liquid crystalline phase transition temperature (TC) was investigated. Our results revealed that lipid components, as well as environmental conditions, that reduce the lipid spontaneous curvature and increase the monolayer bending modulus tend to promote formation of discoidal micelles. At temperatures below the gel-to-liquid crystalline phase transition temperature reduced lipid/PEG-lipid miscibility, furthermore, likely contribute to the observed formation of discoidal rather than threadlike micelles. PMID- 17343403 TI - Proteomics uncovers a role for redox in drought tolerance in wheat. AB - Proteomic analysis offers a new approach to identify a broad spectrum of genes that are expressed in living systems. We applied a proteomic approach to study changes in wheat grain in response to drought, a major environmental parameter adversely affecting development and crop yield. Three wheat genotypes differing in genetic background were cultivated in field under well-watered and drought conditions by following a randomized complete block design with four replications. The overall effect of drought was highly significant as determined by grain yield and total dry matter. About 650 spots were reproducibly detected and analyzed on 2-DE gels. Of these, 121 proteins showed significant change under drought condition in at least one of the genotypes. Mass spectrometry analysis using MALDI-TOF/TOF led to the identification of 57 proteins. Two-thirds of identified proteins were thioredoxin (Trx) targets, in accordance with the link between drought and oxidative stress. Further, because of contrasting changes in the tolerant and susceptible genotypes studied, several proteins emerge as key participants in the drought response. In addition to providing new information on the response to water deprivation, the present study offers opportunities to pursue the breeding of wheat with enhanced drought tolerance using identified candidate genetic markers. The 2-DE database of wheat seed proteins is available for public access at http://www.proteome.ir. PMID- 17343404 TI - Selective metabolite and peptide capture/mass detection using fluorous affinity tags. AB - A new and general methodology is described for the targeted enrichment and subsequent direct mass spectrometric characterization of sample subsets bearing various chemical functionalities from highly complex mixtures of biological origin. Specifically, sample components containing a chemical moiety of interest are first selectively labeled with perfluoroalkyl groups, and the entire sample is then applied to a perfluoroalkyl-silylated porous silicon (pSi) surface. Due to the unique hydrophobic and lipophobic nature of the perfluorinated tags, unlabeled sample components are readily removed using simple surface washes, and the enriched sample fraction can then directly be analyzed by desorption/ionization on silicon mass spectrometry (DIOS-MS). Importantly, this fluorous-based enrichment methodology provides a single platform that is equally applicable to both peptide as well as small molecule focused applications. The utility of this technique is demonstrated by the enrichment and mass spectrometric analysis of both various peptide subsets from protein digests as well as amino acids from serum. PMID- 17343405 TI - Extensive cell envelope modulation is associated with virulence in Brucella abortus. AB - Brucella virulence is linked to components of the cell envelope and tightly connected to the function of the BvrR/BvrS sensory-regulatory system. To quantify the impact of BvrR/BvrS on cell envelope proteins, we performed a label-free mass spectrometry-based proteomic analysis of spontaneously released outer membrane fragments from four strains of Brucella abortus (wild type virulent, avirulent bvrR- and bvrS- mutants as well as reconstituted virulent bvrR+ (bvrR-/pbvrR+)). We identified 167 differentially expressed proteins, of which 25 were assigned to the outer membrane. Approximately half of the outer membrane proteins decreased in abundance, whereas half increased. Notably, expression of five Omp3 family proteins decreased whereas five lipoproteins increased in the mutant strains. In the periplasmic space, by contrast, approximately 80% of the 60 differentially expressed proteins were increased in at least one avirulent mutant. Periplasmic proteins are primarily involved in substrate uptake and transport, and a uniform increase in this class may indicate a nutritional stress response, possibly a consequence of defective outer membrane function. Virtually all proteins reverted to wild type levels in the reconstituted virulent bvrR+ strain. We propose that the wide changes in cell envelope protein expression relate to the markedly avirulent phenotype of bvrR- and bvrS- mutants and that Brucella virulence depends on regulatory networks involving cell envelope and metabolism rather than on discrete virulence factors. This model may be relevant to other alpha Proteobacteria harboring BvrR/BvrS orthologous systems known to be essential for parasitism or endosymbiosis. PMID- 17343406 TI - Designed chain architecture for enhanced migration resistance and property preservation in poly(vinyl chloride)/polyester blends. AB - Blends of poly(vinyl chloride) (PVC) and poly(butylene adipate) (PBA) with varying degrees of branching were analyzed with respect to migration resistance during aging in water, preservation of material properties, and thermal stability. Gas chromatography-mass spectrometry, water absorption, weight loss, thermogravimetric analysis, Fourier transform infrared spectroscopy, contact angle, tensile testing, and differential scanning calorimetry were used to analyze the blends before and after aging in water for 6 weeks. Films plasticized with slightly branched polyester maintained their material and mechanical properties best during aging. High degree of branching was accompanied by poor miscibility, increased hydrophilicity, and polydispersity, and highly branched PBA was not favorable as a plasticizer. Strong intermolecular interactions reduced the water absorption and increased the migration resistance of the blends. Polymeric plasticizers with no, low, or moderate degree of branching improved the thermal stability of films compared to films plasticized with a traditional phthalate plasticizer. Proper design of plasticizer architecture led, thus, to improved migration resistance, long-term properties, and thermal stability in PVC/polyester blends. PMID- 17343407 TI - Mixed lignan-neolignans from Tarenna attenuata. AB - Six new mixed lignan-neolignans and 20 known compounds were isolated from the whole plant of Tarenna attenuata. By analysis of physical and spectroscopic data, the structures of the new compounds were elucidated as (1R,5R,6R)-6-{4-O-[2-(1-(4 hydroxy-3-methoxyphenyl))glycerol]-3,5-dimethoxyphenyl}-3,7 dioxabicyclo[3.3.0]octan-2-one (1), 5' '-methoxyhedyotisol A (2), 4' '-O-(8 guaiacylglycerol)buddlenol A (3), 5' '-methoxy-4' '-O-(8 guaiacylglycerol)buddlenol A (4), 4,6-dimethoxy-5-hydroxy-3-hydroxymethyl-2 (3,4,5-trimethoxyphenyl)-2,3-dihydrobenzofuran (5), and 7-O-ethylguaiacylglycerol (6). Compounds 1, 5, 6, and 8 showed potent antioxidant activities against H2O2 induced impairment in PC12 cells, and compounds 1, 2, 5, and 7 scavenged DPPH radical strongly with IC50 values of 72, 87, 45, and 55 microM, respectively. PMID- 17343408 TI - Triterpene saponins from Bacopa monnieri and their antidepressant effects in two mice models. AB - Three new triterpene glycosides, bacopasides VI-VIII (1-3), together with three known analogues, bacopaside I (4), bacopaside II (5), and bacopasaponsin C (6), were isolated from the whole plant of Bacopa monnieri. Compounds 4, 5, and 6 showed antidepressant activity when tested on forced swimming and tail suspension in mice, respectively. PMID- 17343409 TI - Halogenated monoterpene aldehydes from the South African marine alga Plocamium corallorhiza. AB - Four new halogenated monoterpene aldehydes (1-4) have been isolated from the South African marine red alga Plocamium corallorhiza, along with the known compounds 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2E,7-octadiene (5) and 1,4,8 tribromo-3,7-dichloro-3,7-dimethyl-1E,5E-octadiene (10). The structures of the new compounds were determined by interpretation of their spectroscopic data and synthesis and mass spectrometric analysis of their pentafluorobenzyloxime (PFBO) derivatives. PMID- 17343414 TI - Relative and absolute stereochemistry of secondary/secondary diols: low temperature 1H NMR of their bis-MPA esters. AB - Comparison of the room- and low-temperature 1H NMR spectra of the bis-(R)- or bis (S)-MPA ester derivative of an open chain sec,sec-1,2-diol allows the easy determination of its relative stereochemistry and in some cases absolute configuration. If the diol is anti, its absolute configuration can be directly deduced from the signs of DeltadeltaT1T2 for substituents R1/R2, but if the relative stereochemistry of the diol is syn, the assignment of its absolute configuration requires the preparation of two derivatives (both the bis-(R)- and bis-(S)-MPA esters), comparison of their room-temperature 1H NMR spectra, and calculation of the DeltadeltaRS signs for the methines Halpha(R1) and Halpha(R2) and R1/R2 protons. The reliability of these correlations is validated with 17 diols of known absolute configuration used as model compounds. PMID- 17343415 TI - Synthesis and stacked conformations of symmetrical and unsymmetrical oligo-ureas of metaphenylenediamine. AB - The addition of substituted anilines to nitro-substituted isocyanates followed by reduction generates new aniline-substituted ureas, which can be further extended in a one- or two-directional iterative manner to form oligomeric ureas based on a m-phenylenediamine monomer. Oligo-ureas with up to eight urea linkages are reported. Fully N-substituted oligo-ureas are crystalline, and the X-ray crystal structures display ring-stacked conformations. 1H NMR studies indicate that the stacked conformation persists in solution. PMID- 17343416 TI - Synthesis of the antifungal beta-1,3-glucan synthase inhibitor CANCIDAS (caspofungin acetate) from pneumocandin B0. AB - A novel three-step synthesis of the highly functionalized antifungal agent CANCIDAS (caspofungin acetate, 2) is described, starting from the natural product pneumocandin B0 (1). The highlights of the synthesis include a stereoselective formation of a phenylthioaminal, a remarkable chemoselective, high-yielding, one step borane reduction of a primary amide, and a stereoselective substitution of the phenylthioaminal with ethylenediamine producing 2 in a 45% overall yield. PMID- 17343417 TI - Phenyl-calix[4]arene-based fluorescent sensors: cooperative binding for carboxylates. AB - Tetrakis-(4-carbamoylphenyl)-substituted and tetrakis-(4-amidophenyl)-substituted calix[4]arenes as well as the monomeric biphenylcarbamate have been synthesized as fluorescent receptors for anion sensing. Their binding properties with various anions including F-, CH3COO-, Ph-COO-, and H2PO4- were investigated by fluorescence titrations, Job plot experiments, 1H NMR spectroscopies, and ESI-MS measurements. Importantly, we have found that calix[4]arene-based sensors exhibit greatly enhanced binding affinity and selectivity toward carboxylates. The binding associations of tetrakis-(4-carbamoylphenyl)-substituted calix[4]arene for carboxylates are 1-2 orders of magnitude greater than those of the monomeric biphenylcarbamate sensor. Such an enhancement in the binding affinity and selectivity is attributed to the cooperative binding of the multiple ligating groups as revealed from the ab inito DFT calculations. Although tetrakis-(4 amidophenyl)-substituted calix[4]arene exhibited relatively weaker binding affinity toward anions, its superior binding selectivity for acetate ion over fluoride ion is evident. Our results also suggest that carbamate functionality is a useful H-bond donor for hydrogen-bonding interactions in molecular recognition and supramolecular chemistry. PMID- 17343418 TI - Regioselective palladium-catalyzed formate reduction of N-heterocyclic allylic acetates. AB - The regioselective palladium-catalyzed formate reduction of allylic acetates in five- to eight-membered heterocycles is reported. Reduction of allylic acetates under mild conditions using allylpalladium chloride dimer, phosphines, and formic acid/triethylamine in DMF gives the exo-cyclic olefins in good regioselectivities and high yields. Synthetic application in preparing N-tosyl-3-oxo-piperidine is also reported. PMID- 17343419 TI - Axially chiral 2-arylimino-3-aryl-thiazolidine-4-one derivatives: enantiomeric separation and determination of racemization barriers by chiral HPLC. AB - Axially chiral 2-arylimino-3-aryl-thiazolidine-4-ones have been synthesized as racemic mixtures, and each mixture with the exception of 2-(o-chlorophenyl)imino 3-(o-chlorophenyl)-thiazolidine-4-one has been converted to the corresponding 5 benzylidene-2-arylimino-3-aryl-thiazolidine-4-one racemates by reaction with benzaldehyde. The thermally interconvertible enantiomers of each compound have been obtained by enantioselective HPLC separation on columns Chiralpak AD-H and Chiralcel OD-H, and the barriers to racemization have been found to be 98.1-114.1 kJ/mol. The barriers determined were compared to those of structurally related compounds to provide evidence for the stereochemistry of the aryl imino bond. PMID- 17343420 TI - Synthesis of optically active bifunctional building blocks through enantioselective copper-catalyzed allylic alkylation using Grignard reagents. AB - Enantioselective copper-catalyzed allylic alkylations were performed on allylic bromides with a protected hydroxyl or amine functional group using several Grignard reagents and Taniaphos L1 as a ligand. The terminal olefin moiety in the products was transformed into various functional groups without racemization, providing facile access to a variety of versatile bifunctional chiral building blocks. PMID- 17343421 TI - Photophysical, crystallographic, and electrochemical characterization of symmetric and unsymmetric self-assembled conjugated thiopheno azomethines. AB - Novel conjugated azomethines consisting uniquely of thiophene units are presented. The highly conjugated compounds were synthesized by simple condensation of a stable diamino thiophene (2) with its complementary thiophene aldehydes. These interesting nitrogen-containing thiophene units exhibit variable reactivity leading to controlled aldehyde addition. Because of the different amino reactivity, a one-pot synthesis of unsymmetric and symmetric conjugated azomethines with varying number of thiophene units was possible by judicious choice of solvent and careful control of reagent stoichiometry. The resulting covalent conjugated connections are both reductively and hydrolytically resistant. The thermodynamically E isomer is formed uniquely for all of the azomethines synthesized, which is confirmed by crystallographic studies. These also demonstrated that the azomethine bonds and the thiophene units are highly planar and linear. The fluorescence and phosphorescence of the thiopheno azomethines measured are similar to those of thiophene analogues currently used in functional devices, but with the advantage of low triplet formation and band gaps as low as 1.9 eV. The time-resolved and steady-state temperature-dependent photophysics revealed the thiopheno azomethines do not populate extensively their triplet manifold by intersystem crossing. Rather, their excited-state energy is dissipated predominantly by nonradiative means of internal conversion. Quasi reversible electrochemical radical cation formation of the thiophene units was found. These compounds further undergo electrochemically induced oxidative cross coupling, resulting in conjugated products that also exhibit reversible radical cation formation. PMID- 17343423 TI - Preparation of a 7-arylthieno[3,2-d]pyrimidin-4-amine library. AB - A focused kinase library of 7-arylthieno[3,2-d]pyrimidin-4-amine analogues is readily prepared via solution-phase parallel synthesis. This strategy relies on a key cyclization of a 3-aminothiophene-2-carboxamide with a formamide to construct the thienopyrimidine core. Further elaborations of this core via substitution and Suzuki coupling reactions allow the introduction of other diversity points. This methodology is demonstrated through the preparation of a 72-membered library of 7 arylthieno[3,2-d]pyrimidin-4-amines in good yields and high purities. PMID- 17343424 TI - Nanopin plasmonic resonator array and its optical properties. AB - A one-step electron-beam lithography process for the fabrication of a high-aspect ratio nanopin array is presented. Each nanopin is a metal-capped dielectric pillar upon a ring-shaped metallic disc. Highly tunable optical properties and the electromagnetic interplay between the metallic components were studied by experiment and simulation. The two metallic pieces play asymmetrical roles in their coupling to each other due to their drastic size difference. The structure can lead to ultrasensitive surface-enhanced Raman scattering chemical sensor arrays, etc. PMID- 17343425 TI - Synthesis and optical properties of silver nanobars and nanorice. AB - Silver nanobars with rectangular side facets and an average aspect ratio of 2.7 have been synthesized by modifying the concentration of bromide added to a polyol synthesis. Subsequent rounding of nanobars transformed them into nanorice. Due to their anisotropy, nanobars and nanorice exhibit two plasmon resonance peaks, scattering light both in the visible and in the near-infrared regions. With a combination of discrete-dipole approximation calculations and single-nanoparticle spectroscopy, we explored the effect of nanostructure aspect ratio and corner sharpness on the frequency of plasmon resonance. Near-field calculations and surface-enhanced Raman scattering measurements on single particles were performed to show how local field enhancement changes with both the wavelength and polarization of incident light. PMID- 17343426 TI - The Erice Manifesto: for global reform of the safety of medicines in patient care. AB - The science of pharmacovigilance--monitoring and evaluating drug safety issues and communicating them effectively--is a vital activity of worldwide significance in the safeguarding of patient welfare and public health. Its clinical, public health and economic importance has been demonstrated, but it needs to be better understood and appreciated by politicians, the media and the public. Pharmacovigilance is evolving from being a largely reactive discipline, concentrating on the discovery of harm caused by marketed drugs, to a proactive study of their safety, effectiveness and associated risk factors in normal medical practice and use by patients. The Erice Manifesto specifies the challenges which must be addressed to ensure the continuing development and usefulness of the science, in particular: The active involvement of patients and the public in the core debate about the risks and benefits of medicines, and in decisions about their own treatment and health . The development of new ways of collecting, analysing and communicating information about the safety and effectiveness of medicines; open discussion about it and the decisions which arise from it . The pursuit of learning from other disciplines about how phamacovigilance methods can be improved, alongside wide-ranging professional, official and public collaboration . The creation of purposeful, coordinated, worldwide support amongst politicians, officials, scientists, clinicians, patients and the general public, based on the demonstrable benefits of pharmacovigilance to public health and patient safety. PMID- 17343427 TI - Poisons centres and the reporting of adverse drug events: the case for further development. PMID- 17343428 TI - Psychiatric adverse reactions with statins, fibrates and ezetimibe: implications for the use of lipid-lowering agents. AB - The HMG-CoA reductase inhibitors ('statins') have come into widespread use internationally. There has been a long history of their use in New Zealand and this use has increased in recent years. There has also been an increase in the number of reports to the New Zealand Centre for Adverse Reactions Monitoring (CARM) of suspected psychiatric adverse reactions associated with statins. The reactions mentioned in these reports include depression, memory loss, confusion and aggressive reactions. Convincing reports to CARM of recurrence of these reactions upon rechallenge add weight to recent studies reporting serious psychiatric disturbances in association with statin treatment. Aggressive reactions associated with statins are poorly documented in the literature. These observations emphasise the need to be vigilant in looking for these reactions as they can have a significant personal impact on a patient. The observation that other lipid-lowering agents have similar adverse effects supports the hypothesis that decreased brain cell membrane cholesterol may be important in the aetiology of these psychiatric reactions. PMID- 17343429 TI - Safety of agents used to prevent mother-to-child transmission of HIV: is there any cause for concern? AB - Antiretroviral drugs have been used routinely to reduce the risk of mother-to child transmission of HIV infection since 1994, following the AIDS Clinical Trials Group 076 trial, which demonstrated the efficacy of zidovudine in reducing the risk of in utero and intrapartum transmission. The use of antiretroviral drugs in pregnancy varies geographically, with widespread use of highly active antiretroviral therapy (HAART) in resource-rich settings for delaying maternal HIV disease progression as well as the prevention of mother-to-child transmission; however, in low- and middle-income settings, abbreviated prophylactic regimens focus on the perinatal period, with very limited access to HAART to date. The potential risks associated with antiretroviral exposure for pregnant women, fetuses and infants depend on the duration of this exposure as well as the number and type of drugs. As the benefits of HAART regimens in reducing the risk of mother-to-child transmission and in delaying disease progression are so great, their widespread use has been accepted, despite the relative lack of safety data from human pregnancies. Animal studies have suggested an increased risk of malformations associated with exposure to specific antiretroviral drugs, although evidence to support this from human studies is limited. Trials, cohorts and surveillance studies have shown no evidence of an increased risk of congenital malformations associated with in utero exposure to zidovudine, or other commonly used antiretroviral drugs, with an estimated 2-3% prevalence of birth defects (i.e. similar to that seen in the general population). Exposure to prophylactic zidovudine for prevention of mother-to child transmission is associated with a usually mild and reversible, but rarely severe, anaemia in infants. However, a medium-term impact on haematological parameters of antiretroviral-exposed infants has been reported, with small but persistent reductions in levels of neutrophils, platelets and lymphocytes in children up to 8 years of age; the clinical significance of this remains uncertain. To date, there is no evidence to suggest that exposure to antiretroviral drugs in utero or neonatally is associated with an increased risk of childhood cancer, but the potential for mutagenic and carcinogenic effects at older ages cannot be excluded. Nucleoside analogue-related mitochondrial toxicity is well recognised from studies in non-pregnant individuals, whilst animal studies have provided evidence of mitochondrial toxicity resulting from in utero antiretroviral exposure. Clinically evident mitochondrial disease in children with antiretroviral exposure has only been described in Europe, with an estimated 18-month incidence of 'established' mitochondrial dysfunction of 0.26% among exposed children. Regarding pregnancy-related adverse effects, increased risks of prematurity, pre-eclampsia and gestational diabetes mellitus have been reported by a variety of observational studies with varying strengths of evidence and with conflicting results. Based on current knowledge, the immense benefits of antiretroviral prophylaxis in prevention of mother-to-child transmission far outweigh the potential for adverse effects. However, these potential adverse effects require further and longer term monitoring because they are likely to be rare and to occur later in childhood. PMID- 17343431 TI - Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes. AB - BACKGROUND: A significant number of women of childbearing age have schizophrenia or other psychoses. This means that there is a considerable risk of in utero exposure to risperidone due to maternal use. OBJECTIVE: To determine whether in utero exposure to the atypical antipsychotic risperidone is associated with poor pregnancy and fetal/neonatal outcomes. METHODS: A search of the Benefit Risk Management Worldwide Safety database, using a selection of preferred terms from the Medical Dictionary of Regulatory Activities, was performed to identify all cases of pregnancy or fetal/neonatal outcomes reported in association with risperidone treatment from its first market launch (international birth date, 1 June 1993) to 31 December 2004. The main measures were the patterns and reporting rates of pregnancy (stillbirth and spontaneous and induced abortion) and fetal/neonatal outcomes (congenital abnormalities, perinatal syndromes and withdrawal symptoms) for women administered risperidone during pregnancy. RESULTS: Overall, 713 pregnancies were identified in women who were receiving risperidone. Data were considered prospective in 516 of these, and retrospective in the remaining 197 cases. The majority of the known adverse pregnancy and fetal/neonatal outcomes were retrospectively reported. Of the 68 prospectively reported pregnancies with a known outcome, organ malformations and spontaneous abortions occurred 3.8% and 16.9% (when the 15 induced abortions were excluded from the denominator, as they were predominantly undertaken for nonmedical reasons), respectively, a finding consistent with background rates of the general population. There were 12 retrospectively reported pregnancies involving major organ malformations, the most frequently reported of which affected the heart, brain, lip and/or palate. There were 37 retrospectively reported pregnancies involving perinatal syndromes, of which 21 cases involved behavioural or motor disorders. In particular, there was a cluster of cases reporting tremor, jitteriness, irritability, feeding problems and somnolence, which may represent a withdrawal-emergent syndrome. CONCLUSION: This comprehensive review of the Benefit Risk Management Worldwide Safety database for case reports of risperidone exposure during pregnancy represents the largest ever published dataset documenting pregnancy outcomes for women taking the atypical antipsychotic risperidone. It indicates that in utero exposure to risperidone does not appear to increase the risk of spontaneous abortions, structural malformations and fetal teratogenic risk above that of the general population. Self-limited extrapyramidal effects in neonates were observed after maternal exposure to risperidone during the third trimester of pregnancy. Risperidone should only be used during pregnancy if the benefits outweigh the potential risks. PMID- 17343433 TI - Four-component relativistic theory for nuclear magnetic shielding constants: the orbital decomposition approach. AB - The authors present a scheme to simplify four-component relativistic calculations of nuclear magnetic shielding constants. The central idea is to decompose each first order orbital into two terms, one is magnetically balanced and directly leads to the diamagnetic term, and the other is, to leading order of relativity, kinetically balanced and can therefore simply be represented in the basis of unperturbed positive energy states. As a matrix formulation, the present approach is far simpler than other operator theories. Combined with the Dirac-Kohn-Sham ansatz, the nuclear magnetic shielding constants for the Kr, Xe, and Rn atoms as well as the HBr and HI molecules are calculated, and the results compare favorably with those of other schemes. PMID- 17343432 TI - Survey of forged prescriptions to investigate risk of psychoactive medications abuse in France: results of OSIAP survey. AB - OBJECTIVE: To describe patterns of drug diversion from 2001 to 2004 in France and to define different profiles of forged prescriptions. METHODS: Data from a national cross sectional survey carried out each year since 2001 were analysed. A national network of community pharmacies is requested to collect suspect prescriptions during two periods each year in May and November. Data included were date, age and sex of the patient, type of prescription form, drugs and criteria of suspicion. RESULTS: Between 2001 and 2004, a sample of 1710 abnormal prescription forms were analysed. These concerned women in 54% of cases. The average age of those sampled was 47 years. Sixty-one percent of the 597 varieties of medication belonged to the anatomic therapeutic chemical (ATC) nervous system class. The most frequently involved drugs were benzodiazepines and benzodiazepine analogues (flunitrazepam, zolpidem) or opioids (buprenorphine, morphine). Multiple correspondence analysis underlined two opposite profiles for suspicious prescriptions: (i) specific prescription forms for scheduled drugs presented by men aged <45 years involving drugs for the nervous system and presenting the criteria of stolen, falsified and abnormal prescriptions; and (ii) prescription forms presented by women aged >45 years involving cardiovascular and muscular skeletal system drugs, presenting the criteria of alteration to the prescription. CONCLUSION: Analysis of data collected from community pharmacies in the OSIAP (Ordonnances Suspectes Indicateur d'Abus et de Pharmacodependance) survey gives information about patterns of diversion of medication in France. This system is able to evaluate the impact of measures implemented in order to decrease the misuse of drugs and able to identify new patterns of drug diversion. Identification of profiles of suspicious 'prescription forms' could help pharmacists to better identify abnormal prescriptions. A European project has recently been implemented to extend this kind of survey to other countries in Europe. PMID- 17343434 TI - Multinomial tau-leaping method for stochastic kinetic simulations. AB - We introduce the multinomial tau-leaping (MtauL) method for general reaction networks with multichannel reactant dependencies. The MtauL method is an extension of the binomial tau-leaping method where efficiency is improved in several ways. First, tau-leaping steps are determined simply and efficiently using a priori information and Poisson distribution-based estimates of expectation values for reaction numbers over a tentative tau-leaping step. Second, networks are partitioned into closed groups of reactions and corresponding reactants in which no group reactant set is found in any other group. Third, product formation is factored into upper-bound estimation of the number of times a particular reaction occurs. Together, these features allow larger time steps where the numbers of reactions occurring simultaneously in a multichannel manner are estimated accurately using a multinomial distribution. Furthermore, we develop a simple procedure that places a specific upper bound on the total reaction number to ensure non-negativity of species populations over a single multiple-reaction step. Using two disparate test case problems involving cellular processes--epidermal growth factor receptor signaling and a lactose operon model--we show that the tau-leaping based methods such as the MtauL algorithm can significantly reduce the number of simulation steps thus increasing the numerical efficiency over the exact stochastic simulation algorithm by orders of magnitude. PMID- 17343435 TI - Optimization of quantum Monte Carlo wave functions by energy minimization. AB - We study three wave function optimization methods based on energy minimization in a variational Monte Carlo framework: the Newton, linear, and perturbative methods. In the Newton method, the parameter variations are calculated from the energy gradient and Hessian, using a reduced variance statistical estimator for the latter. In the linear method, the parameter variations are found by diagonalizing a nonsymmetric estimator of the Hamiltonian matrix in the space spanned by the wave function and its derivatives with respect to the parameters, making use of a strong zero-variance principle. In the less computationally expensive perturbative method, the parameter variations are calculated by approximately solving the generalized eigenvalue equation of the linear method by a nonorthogonal perturbation theory. These general methods are illustrated here by the optimization of wave functions consisting of a Jastrow factor multiplied by an expansion in configuration state functions (CSFs) for the C2 molecule, including both valence and core electrons in the calculation. The Newton and linear methods are very efficient for the optimization of the Jastrow, CSF, and orbital parameters. The perturbative method is a good alternative for the optimization of just the CSF and orbital parameters. Although the optimization is performed at the variational Monte Carlo level, we observe for the C2 molecule studied here, and for other systems we have studied, that as more parameters in the trial wave functions are optimized, the diffusion Monte Carlo total energy improves monotonically, implying that the nodal hypersurface also improves monotonically. PMID- 17343430 TI - Drug-induced endocrine and metabolic disorders. AB - Complex interactions exist amongst the various components of the neuroendocrine system in order to maintain homeostasis, energy balance and reproductive function. These components include the hypothalamus-pituitary- adrenal and gonadal axes, the renin-angiotensin-aldosterone system, the sympathetic nervous system and the pancreatic islets. These hormones, peptides and neurotransmitters act in concert to regulate the functions of many organs, notably the liver, muscles, kidneys, thyroid, bone, adrenal glands, adipocytes, vasculature, intestinal tract and gonads, through many intermediary pathways. Endocrine and metabolic disorders can arise from imbalance amongst numerous hormonal factors. These disturbances may be due to endogenous processes, such as increased secretion of hormones from a tumour, as well as exogenous drug administration. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the hormonal axis, effects on hormonal transport, binding, and signalling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can affect the evaluation of endocrine parameters by causing interference with diagnostic tests. Common drug-induced endocrine and metabolic disorders include disorders of carbohydrate metabolism, electrolyte and calcium abnormalities, as well as drug-induced thyroid and gonadal disorders. An understanding of the proposed mechanisms of these drug effects and their evaluation and differential diagnosis may allow for more critical interpretation of the clinical observations associated with such disorders, better prediction of drug-induced adverse effects and better choices of and rationales for treatment. PMID- 17343436 TI - Explicit symplectic integrators of molecular dynamics algorithms for rigid-body molecules in the canonical, isobaric-isothermal, and related ensembles. AB - The authors propose explicit symplectic integrators of molecular dynamics (MD) algorithms for rigid-body molecules in the canonical and isobaric-isothermal ensembles. They also present a symplectic algorithm in the constant normal pressure and lateral surface area ensemble and that combined with the Parrinello Rahman algorithm. Employing the symplectic integrators for MD algorithms, there is a conserved quantity which is close to Hamiltonian. Therefore, they can perform a MD simulation more stably than by conventional nonsymplectic algorithms. They applied this algorithm to a TIP3P pure water system at 300 K and compared the time evolution of the Hamiltonian with those by the nonsymplectic algorithms. They found that the Hamiltonian was conserved well by the symplectic algorithm even for a time step of 4 fs. This time step is longer than typical values of 0.5-2 fs which are used by the conventional nonsymplectic algorithms. PMID- 17343437 TI - Symmetry-adapted-cluster/symmetry-adapted-cluster configuration interaction methodology extended to giant molecular systems: ring molecular crystals. AB - The symmetry adapted cluster (SAC)/symmetry adapted cluster configuration interaction (SAC-CI) methodology for the ground, excited, ionized, and electron attached states of molecules was extended to giant molecular systems. The size extensivity of energy and the size intensivity of excitation energy are very important for doing quantitative chemical studies of giant molecular systems and are designed to be satisfied in the present giant SAC/SAC-CI method. The first extension was made to giant molecular crystals composed of the same molecular species. The reference wave function was defined by introducing monomer-localized canonical molecular orbitals (ml-CMO's), which were obtained from the Hartree Fock orbitals of a tetramer or a larger oligomer within the electrostatic field of the other part of the crystal. In the SAC/SAC-CI calculations, all the necessary integrals were obtained after the integral transformation with the ml CMO's of the neighboring dimer. Only singles and doubles excitations within each neighboring dimer were considered as linked operators, and perturbation selection was done to choose only important operators. Almost all the important unlinked terms generated from the selected linked operators were included: the unlinked terms are important for keeping size extensivity and size intensivity. Some test calculations were carried out for the ring crystals of up to 10 000-mer, confirming the size extensivity and size intensivity of the calculated results and the efficiency of the giant method in comparison with the standard method available in GAUSSIAN 03. Then, the method was applied to the ring crystals of ethylene and water 50-mers, and formaldehyde 50-, 100-, and 500-mers. The potential energy curves of the ground state and the polarization and electron transfer-type excited states were calculated for the intermonomer distances of 2.8-100 A. Several interesting behaviors were reported, showing the potentiality of the present giant SAC/SAC-CI method for molecular engineering. PMID- 17343438 TI - Calculation of highly excited vibrational states using a Richardson-Leja-Davidson scheme. AB - An efficient computational scheme for calculating highly excited vibrational eigenstates is proposed, combining a Richardson-Leja spectral filter with a novel version of the Davidson method [J. Comput. Phys. 17, 87 (1975)]. Highly excited eigenstates of the Rb2 and H2O molecules are computed to test and verify the method. On the average less than 2.5 outer recursions per eigenstate are needed. For each outer Davidson recursion, less than 20 inner filter recursions per eigenstate are needed on the average. PMID- 17343439 TI - On the use of local diffusion models for path ensemble averaging in potential of mean force computations. AB - We use a constant velocity steered molecular dynamics (SMD) simulation of the stretching of deca-alanine in vacuum to demonstrate a technique that can be used to create a surrogate processes approximation (SPA) using the time series that come out of SMD simulations. In this article, the surrogate processes are constructed by first estimating a sequence of local parametric diffusion models along a SMD trajectory and then a single global model is constructed by piecing the local models together through smoothing splines (estimation is made computationally feasible by likelihood function approximations). The SPAs are then "bootstrapped" in order to obtain a plausible range of work values associated with a particular SMD realization. This information is then used to assist in estimating a potential of mean force constructed by appealing to the Jarzynski equality. When this procedure is repeated for a small number of SMD paths, it is shown that the global models appear to come from a single family of closely related diffusion processes. Possible techniques for exploiting this observation are also briefly discussed. The findings of this paper have potential relevance to computationally expensive computer simulations and experimental works involving optical tweezers where it is difficult to collect a large number of samples, but possible to sample accurately and frequently in time. PMID- 17343440 TI - The effective local potential method: implementation for molecules and relation to approximate optimized effective potential techniques. AB - We have recently formulated a new approach, named the effective local potential (ELP) method, for calculating local exchange-correlation potentials for orbital dependent functionals based on minimizing the variance of the difference between a given nonlocal potential and its desired local counterpart [V. N. Staroverov et al., J. Chem. Phys. 125, 081104 (2006)]. Here we show that under a mildly simplifying assumption of frozen molecular orbitals, the equation defining the ELP has a unique analytic solution which is identical with the expression arising in the localized Hartree-Fock (LHF) and common energy denominator approximations (CEDA) to the optimized effective potential. The ELP procedure differs from the CEDA and LHF in that it yields the target potential as an expansion in auxiliary basis functions. We report extensive calculations of atomic and molecular properties using the frozen-orbital ELP method and its iterative generalization to prove that ELP results agree with the corresponding LHF and CEDA values, as they should. Finally, we make the case for extending the iterative frozen-orbital ELP method to full orbital relaxation. PMID- 17343441 TI - Gaussian-4 theory. AB - The Gaussian-4 theory (G4 theory) for the calculation of energies of compounds containing first- (Li-F), second- (Na-Cl), and third-row main group (K, Ca, and Ga-Kr) atoms is presented. This theoretical procedure is the fourth in the Gaussian-n series of quantum chemical methods based on a sequence of single point energy calculations. The G4 theory modifies the Gaussian-3 (G3) theory in five ways. First, an extrapolation procedure is used to obtain the Hartree-Fock limit for inclusion in the total energy calculation. Second, the d-polarization sets are increased to 3d on the first-row atoms and to 4d on the second-row atoms, with reoptimization of the exponents for the latter. Third, the QCISD(T) method is replaced by the CCSD(T) method for the highest level of correlation treatment. Fourth, optimized geometries and zero-point energies are obtained with the B3LYP density functional. Fifth, two new higher level corrections are added to account for deficiencies in the energy calculations. The new method is assessed on the 454 experimental energies in the G305 test set [L. A. Curtiss, P. C. Redfern, and K. Raghavachari, J. Chem. Phys. 123, 124107 (2005)], and the average absolute deviation from experiment shows significant improvement from 1.13 kcal/mol (G3 theory) to 0.83 kcal/mol (G4 theory). The largest improvement is found for 79 nonhydrogen systems (2.10 kcal/mol for G3 versus 1.13 kcal/mol for G4). The contributions of the new features to this improvement are analyzed and the performance on different types of energies is discussed. PMID- 17343442 TI - Dynamics of dissociative recombination versus electron ejection in single rovibronic resonances of BH. AB - Optical-optical-optical triple resonance spectroscopy isolates transitions to vibrationless Rydberg states of BH with principal quantum numbers from n=7 to 50. Corresponding resonances appear in the excitation spectrum of excited boron atoms produced by the dissociative relaxation of these states. The decay to neutral products occurs on a nanosecond time scale. Yet, corresponding resonances show Fano coupling widths that approach 1 cm-1. Above threshold, spontaneous ionization dominates, but line shapes match for resonances with the same electron orbital quantum numbers built on v+=0 and v+=1 cores. This striking feature-for feature similarity in predissociation and autoionization line shapes affirms that inelastic electron-cation scattering pathways leading to electron ejection and dissociative recombination proceed through a common continuum. PMID- 17343443 TI - Oscillator strengths and radiative lifetimes for C2: Swan, Ballik-Ramsay, Phillips, and d 3Pig<--c 3Sigmau+ systems. AB - High level ab initio calculations, using multireference configuration interaction (MRCI) techniques, have been carried out to investigate the spectroscopic properties of the singlet A 1Piu<--X 1Sigmag+ Phillips, the triplet d 3Pig<--a 3Sigmau Swan, the b 3Sigmag-<--a 3Piu Ballik-Ramsay, and the d 3Pig<--c 3Sigmau+ transitions of C2. The MRCI expansions are based on full-valence complete active space self-consistent-field reference states and utilize the aug-cc-pV6Z basis set to resolve valence electron correlation. Core and core-valence correlations and scalar relativistic energy corrections were also incorporated in the computed potential energy surfaces. Nonadiabatic and spin-orbit effects were explored and found to be of negligible importance in the calculations. Harmonic frequencies and rotational constants are typically within 0.1% of experiment. The calculated radiative lifetimes compare very well with the available experimental data. Oscillator strengths are reported for all systems: fv'v", where 0CH3+H2 reaction have been presented. Both the electronic structure calculations and the nuclear dynamics calculations are converged with respect to the basis sets employed. In this paper, the authors apply the same methodology to an isotopic variant of this reaction: D+CH4-->CH3+HD. Accurate rate constants are presented for temperatures between 250 and 400 K. For temperatures between 400 and 800 K, they use a harmonic extrapolation to obtain approximate rate constants for H/D+CH4. The calculations suggest that the experimentally reported rate constants for D+CH4 are about a factor of 10-20 too high. For H+CH4, more accurate experiments are available and agreement is much better: the difference is less than a factor of 2.6. The kinetic isotope effect for the H/D+CH4 reactions is studied and compared with experiment and transition state theory (TST) calculations. Harmonic TST was found to provide a good description of the kinetic isotope effect. PMID- 17343445 TI - Gas phase spectra of all-benzenoid polycyclic aromatic hydrocarbons: triphenylene. AB - The jet-cooled laser-induced fluorescence and dispersed fluorescence spectra of the S1(A1')<--S0(A1') transition of triphenylene are reported. The spectra exhibit false origins of e' symmetry which are modeled by performing calculations of Herzberg-Teller coupling using time-dependent density functional theory. It is found that this level of theory reproduces the main features of the observed spectra. The oscillator strength of the strongest band is calculated to be f=7x10(-4). From a combination of theory and the observed upper state lifetime of 41 ns, an estimate of the fluorescence yield is made of PhiF=0.084, in agreement with previous studies in the condensed phase. PMID- 17343446 TI - Interacting resonances in the F+H2 reaction revisited: complex terms, Riemann surfaces, and angular distributions. AB - We study the effect of overlapping resonances on the angular distributions of the reaction F+H2(v=0,j=0)-->HF(v=2,j=0)+H in the collision energy range from 5 to 65 meV, i.e., under the reaction barrier. Reactive scattering calculations were performed using the hyperquantization algorithm on the potential energy surface of Stark and Werner [J. Chem. Phys. 104, 6515 (1996)]. The positions of the Regge and complex energy poles are obtained by Pade reconstruction of the scattering matrix element. The Sturmian theory is invoked to relate the Regge and complex energy terms. For two interacting resonances, a two-sheet Riemann surface is contracted and inverted. The semiclassical complex angular momentum analysis is used to decompose the scattering amplitude into the direct and resonance contributions. PMID- 17343447 TI - Ground state structures and photoelectron spectroscopy of [Com(coronene)]- complexes. AB - A synergistic approach involving theory and experiment has been used to study the structure and properties of neutral and negatively charged cobalt-coronene [Com(coronene)] complexes. The calculations are based on density functional theory with generalized gradient approximation for exchange and correlation potential, while the experiments are carried out using photoelectron spectroscopy of mass selected anions. The authors show that the geometries of neutral and anionic Co(coronene) and Co2(coronene) are different from those of the corresponding iron-coronene complexes and that both the Co atom and the dimer prefer to occupy eta2-bridge binding sites. However, the magnetic coupling between the Co atoms remains ferromagnetic as it is between iron atoms supported on a coronene molecule. The accuracy of the theoretical results is established by comparing the calculated vertical detachment energies, and adiabatic electron affinities with their experimental data. PMID- 17343448 TI - Femtosecond dynamics of Cu(CD3OD). AB - We report the femtosecond nuclear dynamics of Cu(CD3OD) van der Waals clusters, investigated using photodetachment-photoionization spectroscopy. Photodetachment of an electron from Cu-(CD3OD) with a 150 fs, 398 nm laser pulse produces a vibrationally excited neutral complex that undergoes ligand reorientation and dissociation. The dynamics of Cu(CD3OD) on the neutral surface is interrogated by delayed femtosecond resonant two-photon ionization. Analysis of the resulting time-dependent signals indicates that the nascent Cu(CD3OD) complex dissociates on two distinct time scales of 3 and 30 ps. To understand the origins of the observed time scales, complimentary studies were performed. These included measurement of the photoelectron spectrum of Cu-(CD3OD) as well as a series of calculations of the structure and the electronic and vibrational energies of the anion and neutral complexes. Based on the comparisons of the experimental and calculated results for Cu(CD3OD) with those obtained from earlier studies of Cu(H2O), we conclude that the 3 ps time scale reflects the energy transfer from the rotation of CD3OD in the complex to the dissociation coordinate, while the 30 ps time scale reflects the energy transfer from the excited methyl torsion states to the dissociation coordinate. PMID- 17343449 TI - Dissociative wave packets and dynamic resonances. AB - The authors examine the role of dynamic resonances in laser driven molecular fragmentation. The yields of molecular fragments can undergo dramatic changes as an impulsively excited dissociative wave packet passes through a dynamic resonance. The authors compare three different kinds of dynamic resonances in a series of molecular families and highlight the possibility of characterizing the dissociative wave function as it crosses the resonance location. PMID- 17343450 TI - Fragmentation of methyl chloride studied by partial positive and negative ion yield spectroscopy. AB - The authors present partial-ion-yield experiments on the methyl chloride molecule excited in the vicinity of the Cl2p and C1s inner shells. A large number of fragments, cations produced by dissociation or recombination processes, as well as anionic species, have been detected. Although the spectra exhibit different intensity distributions depending on the core-excited atom, general observations include strong site-selective fragmentation along the C-Cl bond axis and a strong intensity dependence of transitions involving Rydberg series on fragment size. PMID- 17343451 TI - Predissociation of Bi2 A(0u+), v'=21-39. AB - Collisionless lifetimes for Bi2 A(0u+), v'=20-39, J'X) spectrum required both traditional lifetime measurements and synthetic spectrum fits to laser excitation spectra to determine the full range of observed rates. A single, repulsive potential responsible for the observed A-state predissociation could not be identified to adequately describe the vibrational dependence of the predissociation rates. PMID- 17343452 TI - Ionization induced relaxation in solvation structure: a comparison between Na(H2O)n and Na(NH3)n. AB - The constant ionization potential for hydrated sodium clusters Na(H2O)n just beyond n=4, as observed in photoionization experiments, has long been a puzzle in violation of the well-known (n+1)(-1/3) rule that governs the gradual transition in properties from clusters to the bulk. Based on first principles calculations, a link is identified between this puzzle and an important process in solution: the reorganization of the solvation structure after the removal of a charged particle. Na(H2O)n is a prototypical system with a solvated electron coexisting with a solvated sodium ion, and the cluster structure is determined by a balance among three factors: solute-solvent (Na+-H2O), solvent-solvent (H2O-H2O), and electron-solvent (OH{e}HO) interactions. Upon the removal of an electron by photoionization, extensive structural reorganization is induced to reorient OH{e}HO features in the neutral Na(H2O)n for better Na+-H2O and H2O-H2O interactions in the cationic Na+(H2O)n. The large amount of energy released, often reaching 1 eV or more, indicates that experimentally measured ion signals actually come from autoionization via vertical excitation to high Rydberg states below the vertical ionization potential, which induces extensive structural reorganization and the loss of a few solvent molecules. It provides a coherent explanation for all the peculiar features in the ionization experiments, not only for Na(H2O)n but also for Li(H2O)n and Cs(H2O)n. In addition, the contrast between Na(H2O)n and Na(NH3)n experiments is accounted for by the much smaller relaxation energy for Na(NH3)n, for which the structures and energetics are also elucidated. PMID- 17343453 TI - Anomalous nonlinear dielectric and Kerr effect relaxation steady state responses in superimposed ac and dc electric fields. AB - It is shown how the rotational diffusion model of polar molecules (which may be described in microscopic fashion as the diffusion limit of a discrete time random walk on the surface of the unit sphere) may be extended to anomalous nonlinear dielectric relaxation and the dynamic Kerr effect by using a fractional kinetic equation. This fractional kinetic equation (obtained via a generalization of the noninertial kinetic equation of conventional rotational diffusion to fractional kinetics to include anomalous relaxation) is solved using matrix continued fractions yielding the complex nonlinear dielectric susceptibility and the Kerr function of an assembly of rigid dipolar particles acted on by external superimposed dc E0 and ac E1(t)=E1 cos omegat electric fields of arbitrary strengths. In the weak field limit, analytic equations for nonlinear response functions are also derived. PMID- 17343454 TI - Vibrational dynamics and stability of the high-pressure chain and ring phases in S and Se. AB - The high-pressure phases of group-VI elements sulfur and selenium in their spiral chain and ring structures are examined by in situ Raman and x-ray diffraction techniques combined with first principles electronic structure calculations. The S-II, S-III, Se-I, and Se-VII having spiral chain structures and S-VI with a molecular six-member ring structure are studied in a wide P-T range. The square spiral chain structure of S-III and Se-VII is characterized by seven Raman modes that harden with increasing pressure. The calculations reproduce the observed frequencies and allow the authors to make the mode assignment. The "p-S" and "hplt" phases of sulfur reported by previous Raman studies are identified as S-II and S-III with the triangular and square spiral chain structures, respectively. The phase relations obtained by the x-ray and Raman measurements show that the high-pressure high-temperature phases of sulfur, observed by x-ray, can be induced by laser illumination at room temperature. PMID- 17343455 TI - Intermolecular polarizability dynamics of aqueous formamide liquid mixtures studied by molecular dynamics simulations. AB - A molecular dynamics simulation study is presented for the relaxation of the polarizability anisotropy in liquid mixtures of formamide and water, using a dipolar induction scheme that involves the intrinsic polarizability and first hyperpolarizability tensors of the molecules, and the dipole-quadrupole polarizability of water species. The long time diffusive decay of the collective polarizability anisotropy correlations exhibits a substantial slowing down as the formamide mole fraction increases in the mixture. The diffusive times for the polarizability relaxation obtained from the authors' simulations are in good agreement with optical Kerr effect experimental data, and they are found to correlate nearly linearly with the estimated mean lifetimes of the hydrogen bonds within the mixture, suggesting that the relaxation of the hydrogen bond network is responsible to some extent for the collective relaxation of the polarizability anisotropy of the mixture. The short time behavior of the polarizability anisotropy relaxation was investigated by computing the nuclear response function, R(t), which is very rapidly dominated by the formamide contribution as it is added to water, due to the much larger polarizability anisotropy of formamide molecules compared to that of water. Several contributions to the Raman spectrum were also analyzed as a function of composition, and the dynamical origin of the different bands was determined. PMID- 17343456 TI - Size dependence of the structures and energetic and electronic properties of gold clusters. AB - The structures and stabilities of gold clusters with up to 14 atoms have been determined by density-functional theory. The structure optimizations and frequency analysis are performed with the Perdew-Wang 1991 gradient-corrected functional combined with the effective core potential and corresponding valence basis set (LANL2DZ). The turnover point from two-dimensional to three-dimensional geometry for gold clusters occurs at Au12. The energetic and electronic properties of the small gold clusters are strongly dependent on sizes and structures, which are in good agreement with experiment and other theoretical calculations. The even-odd oscillation in cluster stability and electronic properties predicted that the clusters with even numbers of atoms were more stable than the neighboring clusters with odd numbers of atoms. The stability and electronic structure properties of gold clusters are also characterized by the maximum hardness principle of chemical reactivity and minimum polarizability principle. PMID- 17343457 TI - Rigid quantum Monte Carlo simulations of condensed molecular matter: water clusters in the n=2-->8 range. AB - The numerical advantage of quantum Monte Carlo simulations of rigid bodies relative to the flexible simulations is investigated for some simple systems. The results show that if high frequency modes in molecular condensed matter are predominantly in the ground state, the convergence of path integral simulations becomes nonuniform. Rigid body quantum parallel tempering simulations are necessary to accurately capture thermodynamic phenomena in the temperature range where the dynamics are influenced by intermolecular degrees of freedom; the stereographic projection path integral adapted for quantum simulations of asymmetric tops is a significantly more efficient strategy compared with Cartesian coordinate simulations for molecular condensed matter under these conditions. The reweighted random series approach for stereographic path integral Monte Carlo is refined and implemented for the quantum simulation of water clusters treated as an assembly of rigid asymmetric tops. PMID- 17343458 TI - Theoretical prediction of multiple fluid-fluid transitions in monocomponent fluids. AB - The authors use the analytical equation of state obtained by the discrete perturbation theory [A. L. Benavides and A. Gil-Villegas, Mol. Phys. 97, 1225 (1999)] to study the phase diagram of fluids with discrete spherical potentials formed by a repulsive square-shoulder plus an attractive square-well interaction (SS+SW). This interaction is characterized by the usual energy and size parameters plus three dimensionless parameters: two of them measuring the widths of the SS and the SW and the third the relative height of the SS. The matter of interest is that, for certain values of the interaction parameters, the SS+SW systems exhibit more than one first-order fluid-fluid transition. The evidence that several real substances (such as water, phosphorus, carbon, and silica, among others) exhibit an extra liquid-liquid transition has drawn interest into the study of interactions responsible for this behavior. The simple SS+SW fluid is one of the systems that, in spite of being spherically symmetric, shows multiple fluid-fluid transitions. In this work the authors investigate systematically the effect on the phase diagram of varying the interaction parameters. The use of an analytical free-energy equation gives a clear thermodynamic picture of the emergence of different types of critical points, throwing new light on the phase behavior of these fluids and thus clarifying previous results obtained by other techniques. The interplay of attractive and repulsive forces with several scale lengths produces very rich phase diagrams, including cases with three critical points. The region of the interaction parameter space where multiple critical points appear is mapped for various families of interactions. PMID- 17343459 TI - Novel quantum mechanical/molecular mechanical method combined with the theory of energy representation: free energy calculation for the Beckmann rearrangement promoted by proton transfers in the supercritical water. AB - The Beckmann rearrangement of acetone oxime promoted by proton transfers in the supercritical water has been investigated by means of the hybrid quantum mechanical/molecular mechanical approach combined with the theory of energy representation (QM/MM-ER) recently developed. The transition state (TS) structures have been explored by ab initio calculations for the reaction of hydrated acetone oxime on the assumption that the reaction is catalyzed by proton transfers along the hydrogen bonds connecting the solute and the solvent water molecules. Up to two water molecules have been considered as reactants that take part in the proton transfers. As a result of the density functional theory calculations with B3LYP functional and aug-cc-pVDZ basis set, it has been found that participation of two water molecules in the reaction reduces the activation free energy by -12.3 kcal/mol. Furthermore, the QM/MM-ER simulations have revealed that the TS is more stabilized than the reactant state in the supercritical water by 2.7 kcal/mol when two water molecules are involved in the reaction. Solvation free energies of the reactant and the TS have been decomposed into terms due to the electronic polarization of the solute, electron density fluctuation, and others to elucidate the origin of the stabilization of the TS as compared with the reactant. It has been revealed that the promotion of the chemical reaction due to the hydration mainly originates from the interaction between the nonpolarized solute and the solvent water molecules at the supercritical state. PMID- 17343460 TI - Effective method to compute Franck-Condon integrals for optical spectra of large molecules in solution. AB - The authors present a new method for the computation of vibrationally resolved optical spectra of large molecules, including the Duschinsky [Acta Physicochim. URSS 7, 551 (1937)] rotation of the normal modes. The method automatically selects the relevant vibronic contributions to the spectrum, independent of their frequency, and it is able to provide fully converged spectra with a quite modest computational time, both in vacuo and in condensed phase. Starting from the rigorous time-dependent expression they discuss indeed in which limits the spectrum of a molecule embedded in a solvent, described as a polarizable continuum, can be computed in a time-independent formalism, defining both nonequilibrium and equilibrium limits. In these cases the polarizable continuum model provides a suitable description of the solvent field. By computing the absorption spectra of anthracene in gas phase and of coumarin C153 in gas phase and cyclohexane, and the phosphorescence spectrum of the unsubstituted coumarin in ethanol they show that the method is fast and efficient. PMID- 17343461 TI - Stability of separation-shifted Lennard-Jones fluids. AB - Ruelle's thermodynamic stability criteria are applied to the separation-shifted Lennard-Jones (SSLJ) fluid, and the domain of its parameters giving "normal" thermodynamic stability in the thermodynamic limit is established. Fluids interacting with the SSLJ both conforming to and breaking these stability criteria were modeled using molecular dynamics computer simulation. For system sizes typical of most simulations, the transition between the two patterns of behavior was found to be smeared out over a range of parameter values. Thermodynamic instability is marked by a collapse of the system into a small "ball" or volume. The collapsed state nevertheless has some statistical mechanical properties typical of systems exhibiting normal thermodynamics (e.g., the kinetic and configurational temperatures were found to be the same in the collapsed state within statistics). PMID- 17343462 TI - Collective rotational dynamics in ionic liquids: a computational and experimental study of 1-butyl-3-methyl-imidazolium tetrafluoroborate. AB - The aim of this study is the analysis of the rotational motion in ionic liquids, in particular, 1-butyl-3-methyl-imidazolium tetrafluoroborate. By comparing single-particle and collective motion it is found that the Madden-Kivelson relation is fairly fulfilled in long-term simulation studies (>100 ns), i.e., the collective reorientation can be predicted by the corresponding single-particle property and the static dipolar correlation factor, GK. Furthermore, simulated reorientation is in accordance with hydrodynamic theories yielding hydrodynamic radii comparable to van der Waals radii. Since viscosity is the central quantity entering hydrodynamic formulas, we calculated and measured the viscosity of our system in order to have two independent cycles of hydrodynamic evaluation, a computational and an experimental one. While the static dielectric constant agrees with dielectric reflectance experiment, the hydrodynamic radii derived from the experiments are much lower as a consequence of enhanced rotational motion. Even more, a considerable dynamic broadening is observed in the experiments. PMID- 17343463 TI - Dissociative scattering of hyperthermal energy CF3+ ions from modified surfaces. AB - Dissociative scattering of CF3+ ions in collision with a self-assembled monolayer surface of fluorinated alkyl thiol on a gold 111 crystal has been studied at low ion kinetic energies (from 29 to 159 eV) using a custom built tandem mass spectrometer with a rotatable second stage energy analyzer and mass spectrometer detectors. Energy and intensity distributions of the scattered fragment ions were measured as a function of the fragment ion mass and scattering angle. Inelastically scattered CF3+ ions were not observed even at the lowest energy studied here. All fragment ions, CF2+, CF+, F+, and C+, were observed at all energies studied with the relative intensity of the highest energy pathway, C+, increasing and that of the lowest energy pathway, CF2+, decreasing with collision energy. Also, the dissociation efficiency of CF3+ decreased significantly as the collision energy was increased to 159 eV. Energy distributions of all fragment ions from the alkyl thiol surface showed two distinct components, one corresponding to the loss of nearly all of the kinetic energy and scattered over a broad angular range while the other corresponding to smaller kinetic energy losses and scattered closer to the surface parallel. The latter process is due to delayed dissociation of collisionally excited ions after they have passed the collision region as excited parent ions. A similar study performed at 74 eV using a LiF coated surface on a titanium substrate resulted only in one process for all fragment ions; corresponding to the delayed dissociation process. The intensity maxima for these fragmentation processes were shifted farther away from the surface parallel compared to the thiol surface. A new mechanism is proposed for the delayed dissociation process as proceeding via projectile ions' neutralization to long-lived highly excited Rydberg state(s), reionization by the potential field between the collision region and entrance to the energy analyzer, and subsequent dissociation several microseconds after collisional excitation. A kinematic analysis of experimental data plotted as velocity Newton diagrams demonstrates that the delayed dissociation process results from the collisions of the ion with the bulk surface; i.e., the self-assembled monolayer surface acts as a bulk surface. A similar analysis for the highly inelastic collision processes shows that these are due to stronger collisions with a fraction of the thiol molecular chain, varying in length (mass) with the ion energy. PMID- 17343464 TI - Cirrus cloud mimics in the laboratory: an infrared spectroscopy study of thin films of mixed ice of water with organic acids and ammonia. AB - The structures of formic and acetic acids deposited on a thin gold substrate held in vacuum at low temperatures and their related water-ice promoted chemistry have been investigated. The condensed water/guest films were taken to act as cirrus cloud "mimics." Such laboratory representations provide a necessary prelude to understanding how low temperature surfaces can affect chemical composition changes in the upper atmosphere. The systems were characterized by reflection absorption infrared spectroscopy and temperature-programmed desorption spectrometry. The interaction behavior of the binary acid ices was compared to that observed when ternary mixtures of water, formic acid, and ammonia were deposited. Differences in the chemistry were observed depending on deposition method: layering or mixing. The more atmospherically relevant codeposition approach showed that at low temperatures, amorphous formic acid can be ionized to its monodentate form by water ice within the bulk rather than on the surface. In contrast, the introduction of ammonia leads to full bidentate ionization on the ice surface. The thermal desorption profiles of codeposited films of water, ammonia, and formic acid indicate that desorption occurs in three stages. The first is a slow release of ammonia between 120 and 160 K, then the main water desorption event occurs with a maximum rate close to 180 K, followed by a final release of ammonia and formic acid at about 230 K originating from nonhydrous ammonium formate on the surface. The behavior of acetic acid is similar to formic acid but shows lesser propensity to ionize in bulk water ice. PMID- 17343465 TI - Direct and indirect causes of Fermi level pinning at the SiO/GaAs interface. AB - The correlation between atomic bonding sites and the electronic structure of SiO on GaAs(001)-c(2x8)/(2x4) was investigated using scanning tunneling microscopy (STM), scanning tunneling spectroscopy (STS), and density functional theory (DFT). At low coverage, STM images reveal that SiO molecules bond Si end down; this is consistent with Si being undercoordinated and O being fully coordinated in molecular SiO. At approximately 5% ML (monolayer) coverage, multiple bonding geometries were observed. To confirm the site assignments from STM images, DFT calculations were used to estimate the total adsorption energies of the different bonding geometries as a function of SiO coverage. STS measurements indicated that SiO pins the Fermi level midgap at approximately 5% ML coverage. DFT calculations reveal that the direct causes of Fermi level pinning at the SiO GaAs(001)-(2x4) interface are a result of either local charge buildups or the generation of partially filled dangling bonds on Si atoms. PMID- 17343466 TI - Electrochemical interface between an ionic liquid and a model metallic electrode. AB - A molecular dynamics simulation model for an electroactive interface in which a metallic electrode is maintained at a preset electrical potential is described. The model, based on earlier work of Siepmann and Sprik [J. Chem. Phys. 102, 511 (1995)], uses variable charges whose magnitudes are adjusted on-the-fly according to a variational procedure to maintain the constant potential condition. As such, the model also allows for the polarization of the electrode by the electrolyte, sometimes described by the introduction of image charges. The model has been implemented in a description of an electrochemical cell as a pair of parallel planar electrodes separated by the electrolyte using a two-dimensional Ewald summation method. The method has been applied to examine the interfacial structure in two ionic liquids, consisting of binary mixtures of molten salts, chosen to exemplify the influences of dissimilar cation size and charge. The stronger coordination of the smaller and more highly charged cations by the anions prevents them from approaching even the negatively charged electrode closely. This has consequences for the capacitance of the electrode and will also have an impact on the rates of electron transfer processes. The calculated capacitances exhibit qualitatively the same dependence on the applied potential as has been observed in experimental studies. PMID- 17343467 TI - First-principles calculation on the conductance of a single 1,4 diisocyanatobenzene molecule with single-walled carbon nanotubes as the electrodes. AB - The conductance of a single 1,4-diisocyanatobenzene molecule sandwiched between two single-walled carbon nanotube (SWCNT) electrodes are studied using a fully self-consistent ab initio approach which combines nonequilibrium Green's function formalism with density functional theory calculations. Several metallic zigzag and armchair SWCNTs with different diameters are used as electrodes; dangling bonds at their open ends are terminated with hydrogen atoms. Within the energy range of a few eV of the Fermi energy, all the SWCNT electrodes couple strongly only with the frontier molecular orbitals that are related to nonlocal pi bonds. Although the chirality of SWCNT electrodes has significant influences on this coupling and thus the molecular conductance, the diameter of electrodes, the distance, and the torsion angle between electrodes have only minor influences on the conductance, showing the advantage of using SWCNTs as the electrodes for molecular electronic devices. PMID- 17343468 TI - Modeling the selective partitioning of cations into negatively charged nanopores in water. AB - Partitioning and transport of water and small solutes into and through nanopores are important to a variety of chemical and biological processes and applications. Here we study water structure in negatively charged model cylindrical [carbon nanotube (CNT)-like] nanopores, as well as the partitioning of positive ions of increasing size (Na+, K+, and Cs+) into the pore interior using extensive molecular dynamics simulations. Despite the simplicity of the simulation system containing a short CNT-like nanopore in water carrying a uniformly distributed charge of qpore=-ne surrounded by n (=0,...,8) cations, making the overall system charge neutral-the results provide new and useful insights on both the pore hydration and ion partitioning. For n=0, that is, for a neutral nanopore, water molecules partition into the pore and form single-file hydrogen-bonded wire spanning the pore length. With increasing n, water molecules enter the pore from both ends with preferred orientations, resulting in a mutual repulsion between oriented water molecules at the pore center and creating a cavity-like low density region at the center. For low negative charge densities on the pore, the driving force for partitioning of positive ions into the pore is weak, and no partitioning is observed. Increasing the pore charge gradually leads to partitioning of positive ions into the pore. Interestingly, over a range of intermediate negative charge densities, nanopores display both thermodynamic as well as kinetic selectivity toward partitioning of the larger K+ and Cs+ ions into their interior over the smaller Na+ ions. Specifically, the driving force is in the order K+>Cs+>Na+, and K+ and Cs+ ions enter the pore much more rapidly than Na+ ions. At higher charge densities, the driving force for partitioning increases for all cations-it is highest for K+ ions-and becomes similar for Na+ and Cs+ ions. The variation of thermodynamic driving force and the average partitioning time with the pore charge density together suggest the presence of free energy barriers in the partitioning process. We discuss the role of ion hydration in the bulk and in the pore interior as well as of the pore hydration in determining the barrier heights for ion partitioning and the observed thermodynamic and kinetic selectivities. PMID- 17343469 TI - Mesoscopic restructuring and mass transport of metal atoms during reduction of the Ag(111)-p(4x4)-O surface with CO. AB - The reduction of the Ag(111)-p(4x4)-O surface oxide with CO was used to study the restructuring of the surface during reaction. Scanning tunneling microscopy images taken during the reaction show the formation of Ag islands and pits within the reacted areas surrounded by unreacted p(4x4)-O. The number of Ag adatoms incorporated in the Ag(111)-p(4x4)-O structure was determined to be 12 from the areas of these islands and pits. The evolution of the reacted area with exposure to CO indicates that direct reaction with the Ag(111)-p(4x4)-O is not preferred, but that the boundary between the p(4x4) and the freshly created Ag(111) surface is the source of the reactive oxygen. PMID- 17343470 TI - A coarse grain model for DNA. AB - Understanding the behavior of DNA at the molecular level is of considerable fundamental and engineering importance. While adequate representations of DNA exist at the atomic and continuum level, there is a relative lack of models capable of describing the behavior of DNA at mesoscopic length scales. We present a mesoscale model of DNA that reduces the complexity of a nucleotide to three interactions sites, one each for the phosphate, sugar, and base, thereby rendering the investigation of DNA up to a few microns in length computationally tractable. The charges on these sites are considered explicitly. The model is parametrized using thermal denaturation experimental data at a fixed salt concentration. The validity of the model is established by its ability to predict several aspects of DNA behavior, including salt-dependent melting, bubble formation and rehybridization, and the mechanical properties of the molecule as a function of salt concentration. PMID- 17343471 TI - Surface enhanced optical absorption and photoluminescence in nonbonding electrons in small poly(vinylpyrrolidone) molecules. AB - Molecularly dispersed poly(vinylpyrrolidone) (PVP) in water (after mechanochemical stirring in hot condition) absorbs strongly in a triplet band (pi ->pi* electronic transitions) in the 200-400 nm range. Absorption maximum shifts nonlinearly from 222 nm [full width at half maximum (FWHM) approximately 22 nm] in a dilute solution 0.1 g/dl PVP to a value as large as 247 nm (FWHM approximately 55 nm) in 10 g/dl PVP. Disobeying the Beer-Lambert relation, the absorbance increased in dilute samples. Irradiating in this region induces two emission groups; (i) 300-580 nm and (ii) 600-850 nm in six distinct bands in three major PVP conformers. The first band group involves an order of larger intensity in the other group. Strong electron-phonon coupling results in the C=O group of pyrrolidone ring, which governs the conformation, in a vibronic band 1665 cm-1 as intense as the (0,0) band. The group (ii) occurs in part of the energy loss in interactions of excited photons with surrounding in the n<--pi* transition [band group (i)] in the nonbonding C=O (2sp4) electrons. Such transitions may be useful for optical switching and other devices. PMID- 17343472 TI - Coupled-cluster and explicitly correlated perturbation-theory calculations of the uracil anion. AB - A valence-type anion of the canonical tautomer of uracil has been characterized using explicitly correlated second-order Moller-Plesset perturbation theory (RI MP2-R12) in conjunction with conventional coupled-cluster theory with single, double, and perturbative triple excitations. At this level of electron correlation treatment and after inclusion of a zero-point vibrational energy correction, determined in the harmonic approximation at the RI-MP2 level of theory, the valence anion is adiabatically stable with respect to the neutral molecule by 40 meV. The anion is characterized by a vertical detachment energy of 0.60 eV. To obtain accurate estimates of the vertical and adiabatic electron binding energies, a scheme was applied in which electronic energy contributions from various levels of theory were added, each of them extrapolated to the corresponding basis-set limit. The MP2 basis-set limits were also evaluated using an explicitly correlated approach, and the results of these calculations are in agreement with the extrapolated values. A remarkable feature of the valence anionic state is that the adiabatic electron binding energy is positive but smaller than the adiabatic electron binding energy of the dipole-bound state. PMID- 17343475 TI - Photoacoustic imaging of the microvasculature with a high-frequency ultrasound array transducer. AB - Visualization of microvascular networks could provide new information about function and disease. We demonstrate the capabilities of a 30-MHz ultrasound array system for photoacoustic microscopy of small (< or = 300 microm) vessels in a rat. 3D images obtained by translating the array in the elevation direction are compared with photographs of excised skin. The system is shown to have 100-microm lateral resolution, 25-microm axial resolution, and 3-mm imaging depth. To our knowledge this is the first report on photoacoustic microscopy of the microvasculature with a high-frequency array transducer. It is anticipated that the system can be used for studying and diagnosing a number of diseases including cancer, atherosclerosis, dermatological disorders, and peripheral microvascular complications in diabetes. PMID- 17343476 TI - Real-time optoacoustic monitoring of vascular damage during photodynamic therapy treatment of tumor. AB - The optoacoustic technique is a noninvasive imaging method with high spatial resolution. It potentially can be used to monitor anatomical and physiological changes. Photodynamic therapy (PDT)-induced vascular damage is one of the important mechanisms of tumor destruction, and real-time monitoring of vascular changes can have therapeutic significance. A unique optoacoustic system is developed for neovascular imaging during tumor phototherapy. In this system, a single-pulse laser beam is used as the light source for both PDT and for concurrently generating ultrasound signals for optoacoustic imaging. To demonstrate its feasibility, this system is used to observe vascular changes during PDT treatment of chicken chorioallantoic membrane (CAM) tumors. The photosensitizer used in this study is protoporphyrin IX (PpIX) and the laser wavelength is 532 nm. Neovascularization in tumor angiogenesis is visualized by a series of optoacoustic images at different stages of tumor growth. Damage of the vascular structures by PDT is imaged before, during, and after treatment. Rapid, real-time determination of the size of targeted tumor blood vessels is achieved, using the time difference of positive and negative ultrasound peaks during the PDT treatment. The vascular effects of different PDT doses are also studied. The experimental results show that a pulsed laser can be conveniently used to hybridize PDT treatment and optoacoustic imaging and that this integrated system is capable of quantitatively monitoring the structural change of blood vessels during PDT. This method could be potentially used to guide PDT and other phototherapies using vascular changes during treatment to optimize treatment protocols, by choosing appropriate types and doses of photosensitizers and doses of light. PMID- 17343477 TI - In vivo monitoring of singlet oxygen using delayed chemiluminescence during photodynamic therapy. AB - It is known that singlet oxygen ((1)O(2)) is the main factor mediating cytotoxicity in photodynamic therapy (PDT). The effectiveness of a PDT treatment is directly linked to the (1)O(2) produced in the target. Although the luminescence from (1)O(2) is suggested as an indicator for evaluating photodynamic therapy, the inherent disadvantages limit its potential for in vivo applications. We have previously reported that chemiluminescence can be used to detect (1)O(2) production in PDT and have linked the signal to the cytotoxicity. We further our investigation for monitoring (1)O(2) production during PDT. The lifetime of 3,7-dihydro-6-{4-[2-(N(')-(5-fluoresceinyl)thioureido)ethoxy]phenyl} 2-methylimidazo {1,2-a} pyrazin-3-one-chemiluminescence (FCLA-CL) is evaluated, and the results show that it is much longer than that of direct luminescence of (1)O(2). A gated measurement algorithm is developed to fully utilize the longer lifetime for a clean measurement of the CL without the interference from the irradiation light. The results show that it is practically feasible to use the technique to monitor the (1)O(2). Compared to the direct (1)O(2) luminescence measurement, our new technique is sensitive and can be realized with a conventional optical detector with excellent signal-to-noise ratio. It thus provides a means for real-time in vivo monitoring of (1)O(2) production during PDT. PMID- 17343478 TI - Determination of fluence rate and temperature distributions in the rat brain; implications for photodynamic therapy. AB - Light and heat distributions are measured in a rat glioma model used in photodynamic therapy. A fiber delivering 632-nm light is fixed in the brain of anesthetized BDIX rats. Fluence rates are measured using calibrated isotropic probes that are positioned stereotactically. Mathematical models are then used to derive tissue optical properties, enabling calculation of fluence rate distributions for general tumor and light application geometries. The fluence rates in tumor-free brains agree well with the models based on diffusion theory and Monte Carlo simulation. In both cases, the best fit is found for absorption and reduced scattering coefficients of 0.57 and 28 cm(-1), respectively. In brains with implanted BT(4)C tumors, a discrepancy between diffusion and Monte Carlo-derived two-layer models is noted. Both models suggest that tumor tissue has higher absorption and less scattering than normal brain. Temperatures are measured by inserting thermocouples directly into tumor-free brains. A model based on diffusion theory and the bioheat equation is found to be in good agreement with the experimental data and predict a thermal penetration depth of 0.60 cm in normal rat brain. The predicted parameters can be used to estimate the fluences, fluence rates, and temperatures achieved during photodynamic therapy. PMID- 17343479 TI - Hybrid phosphorescence and fluorescence native spectroscopy for breast cancer detection. AB - Fluorescence and phosphorescence measurements are performed on normal and malignant ex vivo human breast tissues using UV LED and xenon lamp excitation. Tryptophan (trp) phosphorescence intensity is higher in both normal glandular and adipose tissue when compared to malignant tissue. An algorithm based on the ratio of trp fluorescence intensity at 345 nm to phosphorescence intensity at 500 nm is successfully used to separate normal from malignant tissue types. Normal specimens consistently exhibited a low I(345)I(500) ratio (<10), while for malignant specimens, the I(345)I(500) ratio is consistently high (>15). The ratio analysis correlates well with histopathology. Intensity ratio maps with a spatial resolution of 0.5 mm are generated in which local regions of malignancy could be identified. PMID- 17343480 TI - Fluorescence polarization of tetracycline derivatives as a technique for mapping nonmelanoma skin cancers. AB - Nonmelanoma skin cancer is the most common form of human cancer, often resulting in high morbidity. Low visual contrast of these tumors makes their delineation a challenging problem. Employing a linearly polarized monochromatic light source and a wide-field CCD camera, we have developed a technique for fluorescence polarization imaging of the nonmelanoma cancers stained using antibiotics from the tetracycline family. To determine the feasibility of the method, fluorescence polarization images of 86 thick, fresh cancer excisions were studied. We found that the level of endogenous fluorescence polarization was much lower than that of exogenous, and that the average values of fluorescence polarization of tetracycline derivatives were significantly higher in cancerous as compared to normal tissue. Out of 86 tumors [54 stained in demeclocycline (DMN) and 32 in tetracycline (TCN)], in 79 cases (51-DMN, 28-TCN) the location, size, and shape of the lesions were identified accurately. The results of this trial indicate that nonmelanoma skin tumors can be distinguished from healthy tissue based on the differences in exogenous fluorescence polarization of TCN and/or DMN. Therefore, the developed technique can provide an important new tool for image guided cancer surgery. PMID- 17343481 TI - Analysis of facial sebum distribution using a digital fluorescent imaging system. AB - Current methods for analysis of sebum excretion have limitations, such as irreproducible results in repeatable measurements due to the point measurement method, user-dependent artifacts due to contact measurement or qualitative evaluation of the image, and long measurement time. A UV-induced fluorescent digital imaging system is developed to acquire facial images so that the distribution of sebum excretion on the face could be analyzed. The imaging system consists of a constant UV-A light source, digital color camera, and head positioning device. The system for acquisition of a fluorescent facial image and the image analysis method is described. The imaging modality provides uniform light distribution and presents a discernible color fluorescent image. Valuable parameters of sebum excretion are obtained after image analysis. The imaging system, which provides a noncontact method, is proved to be a useful tool to evaluate the amount and pattern of sebum excretion. When compared to conventional "Wood's lamp" and "Sebutape" methods that provide similar parameters for sebum excretion, the described method is simpler and more reliable to evaluate the dynamics of sebum excretion in nearly real-time. PMID- 17343482 TI - Laser confocal endomicroscopy as a novel technique for fluorescence diagnostic imaging of the oral cavity. AB - Malignancies of the oral cavity are conventionally diagnosed by white light endoscopy, biopsy, and histopathology. However, it is often difficult to distinguish between benign and premalignant or early lesions. A laser confocal endomicroscope (LCE) offers noninvasive, in vivo surface and subsurface fluorescence imaging of tissue. We investigate the use of an LCE with a rigid probe for diagnostic imaging of the oral cavity. Fluorescein and 5-aminolevulinic acid (ALA) were used to carry out fluorescence imaging in vivo and on resected tissue samples of the oral cavity. In human subjects, ALA-induced protoporphyrin IX (PpIX) fluorescence images from the normal tongue were compared to images obtained from patients with squamous cell carcinoma (SCC) of the tongue. Using rat models, images from normal rat tongues were compared to those from carcinogen induced models of SCC. Good structural images of the oral cavity were obtained using ALA and fluorescein, and morphological differences between normal and lesion tissue can be distinguished. The use of a pharmaceutical-grade solvent Pharmasolve enhanced the subsurface depth from which images can be obtained. Our initial results show that laser confocal fluorescence endomicroscopy has potential as a noninvasive optical imaging method for the diagnosis of oral cavity malignancies. PMID- 17343483 TI - Immunofluorescence detection with quantum dot bioconjugates for hepatoma in vivo. AB - The use of highly specific and highly sensitive immunofluorescent probes is a promising approach for biomedical imaging in living tissue. We focus on immunofluorescence with quantum dot bioconjugates for hepatoma detection in vivo. We synthesized specific immunofluorescent probes by linking quantum dots to AFP (alpha-fetoprotein) antibody for specific binding AFP-an important marker for hepatocellular carcinoma cell lines. In in vivo studies, the characteristic quantum dot (QD) fluorescent property is exhibited by the QDs-Anti-AFP probes in tumor and they demonstrate active tumor targeting and spectroscopic hepatoma imaging with an integrated fluorescence imaging system. We investigate the inhomogeneous distribution of the QDs-Anti-AFP probes in tumor by using a site-by site measurement method to test their ability for distribution studies of cancer cells. These results demonstrate the practicality of QD bioconjugates as attractive fluorescent probes for biomedical detection. PMID- 17343484 TI - Three-dimensional imaging of whole rodent organs using optical computed and emission tomography. AB - We explore the potential of optical computed tomography (optical-CT) and optical emission computed tomography (optical-ECT) in a new area-whole organ imaging. The techniques are implemented on an in-house prototype benchtop system with improved image quality and the capacity to image larger samples (up to 3 cm) than previous systems based on stereo microscopes. Imaging performance tests confirm high geometrical accuracy, accurate relative measurement of linear attenuation coefficients, and the ability to image features at the 50-microm level. Optical labeling of organ microvasculature was achieved using two stains deposited via natural in vivo circulatory processes: a passive absorbing ink-based stain and an active fluorescin FITC-lectin conjugate. The lectin protein binds to the endothelial lining, and FITC fluorescense enables optical-ECT imaging. Three dimensional (3-D) optical-CT images have been acquired of a normal rat heart and left lung and a mouse right lung showing exquisite detail of the functional vasculature and relative perfusion distribution. Coregistered optical-ECT images were also acquired of the mouse lung and kidney. Histological sections confirmed effective labeling of microvasculature throughout the organs. The advantages of optical-CT and optical-ECT include the potential for a unique combination of high resolution and high contrast and compatibility with a wide variety of optical probes, including gene expression labeling fluorescent reporter proteins. PMID- 17343485 TI - Index-of-refraction-dependent subcellular light scattering observed with organelle-specific dyes. AB - Angularly resolved light scattering and wavelength-resolved darkfield scattering spectroscopy measurements were performed on intact, control EMT6 cells and cells stained with high-extinction lysosomal- or mitochondrial-localizing dyes. In the presence of the lysosomal-localizing dye NPe6, we observe changes in the details of light scattering from stained and unstained cells, which have both wavelength- and angular-dependent features. Analysis of measurements performed at several wavelengths reveals a reduced scattering cross section near the absorption maximum of the lysosomal-localizing dye. When identical measurements are made with cells loaded with a similar mitochondrial-localizing dye, HPPH, we find no evidence that staining mitochondria had any effect on the light scattering. Changes in the scattering properties of candidate populations of organelles induced by the addition of an absorber are modeled with Mie theory, and we find that any absorber-induced scattering response is very sensitive to the inherent refractive index of the organelle population. Our measurements and modeling are consistent with EMT6-cell-mitochondria having refractive indices close to those reported in the literature for organelles, approximately 1.4. The reduction in scattering cross section induced by NPe6 constrains the refractive index of lysosomes to be significantly higher. We estimate the refractive index of lysosomes in EMT6 cells to be approximately 1.6. PMID- 17343486 TI - Confocal Raman spectroscopic analysis of cross-linked ultra-high molecular weight polyethylene for application in artificial hip joints. AB - Confocal spectroscopic techniques are applied to selected Raman bands to study the microscopic features of acetabular cups made of ultra-high molecular weight polyethylene (UHMWPE) before and after implantation in vivo. The micrometric lateral resolution of a laser beam focused on the polymeric surface (or subsurface) enables a highly resolved visualization of 2-D conformational population patterns, including crystalline, amorphous, orthorhombic phase fractions, and oxidation index. An optimized confocal probe configuration, aided by a computational deconvolution of the optical probe, allows minimization of the probe size along the in-depth direction and a nondestructive evaluation of microstructural properties along the material subsurface. Computational deconvolution is also attempted, based on an experimental assessment of the probe response function of the polyethylene Raman spectrum, according to a defocusing technique. A statistical set of high-resolution microstructural data are collected on a fully 3-D level on gamma-ray irradiated UHMWPE acetabular cups both as-received from the maker and after retrieval from a human body. Microstructural properties reveal significant gradients along the immediate material subsurface and distinct differences are found due to the loading history in vivo, which cannot be revealed by conventional optical spectroscopy. The applicability of the confocal spectroscopic technique is valid beyond the particular retrieval cases examined in this study, and can be easily extended to evaluate in-vitro tested components or to quality control of new polyethylene brands. Confocal Raman spectroscopy may also contribute to rationalize the complex effects of gamma-ray irradiation on the surface of medical grade UHMWPE for total joint replacement and, ultimately, to predict their actual lifetime in vivo. PMID- 17343487 TI - Integrated multimodal microscopy, time-resolved fluorescence, and optical-trap rheometry: toward single molecule mechanobiology. AB - Cells respond to forces through coordinated biochemical signaling cascades that originate from changes in single-molecule structure and dynamics and proceed to large-scale changes in cellular morphology and protein expression. To enable experiments that determine the molecular basis of mechanotransduction over these large time and length scales, we construct a confocal molecular dynamics microscope (CMDM). This system integrates total-internal-reflection fluorescence (TIRF), epifluorescence, differential interference contrast (DIC), and 3-D deconvolution imaging modalities with time-correlated single-photon counting (TCSPC) instrumentation and an optical trap. Some of the structures hypothesized to be involved in mechanotransduction are the glycocalyx, plasma membrane, actin cytoskeleton, focal adhesions, and cell-cell junctions. Through analysis of fluorescence fluctuations, single-molecule spectroscopic measurements [e.g., fluorescence correlation spectroscopy (FCS) and time-resolved fluorescence] can be correlated with these subcellular structures in adherent endothelial cells subjected to well-defined forces. We describe the construction of our multimodal microscope in detail and the calibrations necessary to define molecular dynamics in cell and model membranes. Finally, we discuss the potential applications of the system and its implications for the field of mechanotransduction. PMID- 17343488 TI - Rotation of actin monomers during isometric contraction of skeletal muscle. AB - Cyclic interactions of myosin and actin are responsible for contraction of muscle. It is not self-evident, however, that the mechanical cycle occurs during steady-state isometric contraction where no work is produced. Studying cross bridge dynamics during isometric steady-state contraction requires an equilibrium time-resolved method (not involving application of a transient). This work introduces such a method, which analyzes fluctuations of anisotropy of a few actin molecules in muscle. Fluorescence anisotropy, indicating orientation of an actin protomer, is collected from a volume of a few attoliters (10(-18) L) by confocal total internal reflection (CTIR) microscopy. In this method, the detection volume is made shallow by TIR illumination, and narrow by confocal aperture inserted in the conjugate image plane. The signal is contributed by approximately 12 labeled actin molecules. Shortening of a myofibril during contraction is prevented by light cross-linking with 1-ethyl-3-[3-dimethylamino) propyl]-carbodiimide. The root mean-squared anisotropy fluctuations are greater in isometrically contracting than in rigor myofibrils. The results support the view that during isometric contraction, cross-bridges undergo a mechanical cycle. PMID- 17343489 TI - Visualization of hepatobiliary excretory function by intravital multiphoton microscopy. AB - Intravital imaging of hepatobiliary excretion is vital for elucidating liver metabolism. In this work, we describe a novel method to observe the intravital dynamics of the uptake, processing, and excretion of an organic anion, 6 carboxyfluorescein diacetate (6-CFDA) in the hepatobiliary system. This is achieved by the use of multiphoton microscopy and an intravital hepatic imaging chamber. The high-quality images show sequential uptake and processing of 6-CFDA from the hepatocytes and the subsequent excretion into bile canaliculi within approximately 50 min. This is a promising technique to study intravital hepatic physiology and metabolism. PMID- 17343490 TI - High-resolution whole organ imaging using two-photon tissue cytometry. AB - Three-dimensional (3-D) tissue imaging offers substantial benefits to a wide range of biomedical investigations from cardiovascular biology, diabetes, Alzheimer's disease to cancer. Two-photon tissue cytometry is a novel technique based on high-speed multiphoton microscopy coupled with automated histological sectioning, which can quantify tissue morphology and physiology throughout entire organs with subcellular resolution. Furthermore, two-photon tissue cytometry offers all the benefits of fluorescence-based approaches including high specificity and sensitivity and appropriateness for molecular imaging of gene and protein expression. We use two-photon tissue cytometry to image an entire mouse heart at subcellular resolution to quantify the 3-D morphology of cardiac microvasculature and myocyte morphology spanning almost five orders of magnitude in length scales. PMID- 17343491 TI - Rapid near-infrared diffuse tomography for hemodynamic imaging using a low coherence wideband light source. AB - Rapid near-infrared (NIR) diffuse optical tomography is implemented using a low coherence source. The spectral bandwidth of the low-coherence source is dispersed and coupled to linearly bundled fibers, such that "spread"-spectral encoding among the bundled fibers is formed, and could be used for parallel source illumination onto tissue. In comparison with a previous spectral-encoding technique that employed multiple laser diodes, the use of a low-coherence source for spread-spectral encoding presents a few unique characteristics: (1) it provides shift-free spectral encoding; (2) it reduces the reconstruction uncertainty significantly owing to the minimization of spontaneous channel-to channel intensity fluctuation; and (3) it enables the implementation of NIR tomography into an endoscopic imaging mode. A 20-mW superluminescent diode centered at 840 nm with a 40-nm bandwidth is used as the source, and a sampling speed of 5 Hz is obtained in a 27-mm imaging array consisting of eight sources and eight detection channels. The principles of using a low-coherence source for spread-spectral encoding are elaborated, the characteristic performances are demonstrated, and the preliminary results of imaging hemoglobin absorption variations during 10 s of voluntary breath-holding are presented. PMID- 17343492 TI - Comparative study of optical sources in the near infrared for optical coherence tomography applications. AB - Optical coherence tomography (OCT) is a powerful, noninvasive biomedical technique that uses low-coherence light sources to obtain in-depth scans of biological tissues. We report results obtained with three different sources emitting at 1570, 1330, and 810 nm, respectively. Attenuation and backscattering measurements are obtained with these sources for several in vitro biological tissues. From these measurements, we use a graphical method to make comparisons of the penetration depth and backscattering intensity of each wavelength for the studied samples. The influence of the coherence length of each source is also taken into account in order to make a more relevant comparison. PMID- 17343493 TI - Frequency tracking in optical Doppler tomography using an adaptive notch filter. AB - Optical Doppler tomography is a valuable functional extension of optical coherence tomography (OCT) that can be used to study subsurface blood flows of biological tissues. We propose a novel frequency estimation technique that uses an adaptive notch filter (ANF) to track the depth-resolved Doppler frequency. This new technique is a minimal-parameter filter and works in the time domain without the need of Fourier transformation. Therefore, the algorithm has a computationally efficient structure that may be well suited for implementation in real-time ODT systems. Our simulations and imaging results also demonstrate that this filter has good performance in terms of noise robustness and estimation accuracy compared with existing estimation algorithms. PMID- 17343494 TI - Investigations of the eye fundus using a simultaneous optical coherence tomography/indocyanine green fluorescence imaging system. AB - We develop a dual-channel optical coherence tomography/indocyanine green (OCT/ICG) fluorescence system based on our previously reported ophthalmic OCT/confocal imaging system. The confocal channel is tuned to the fluorescence wavelength range of the ICG dye and light from the same optical source is used to generate the OCT image and to excite the ICG fluorescence. The system enables the clinician to visualize simultaneously en face OCT slices and corresponding ICG angiograms of the ocular fundus, displayed side by side. C-scan (constant depth) and B-scan (cross section) images are collected by fast en face scanning (T scan). The pixel-to-pixel correspondence between the OCT and angiography images enables the user to precisely capture OCT B-scans at selected points on the ICG confocal images. PMID- 17343495 TI - Time-resolved simultaneous measurement of group index and physical thickness during photopolymerization of resin-based dental composite. AB - Light-activated resin-based dental composites are increasingly replacing dental amalgam. However, these materials are limited by inefficient setting reactions as a function of depth that constrain the maximum extent of cure. Insufficient curing can contribute to an overall reduction in biocompatibility of the material. We demonstrate dynamic refractive index measurements of a commercial dental composite throughout cure using spectral domain low coherence interferometry. Our results show a linear relationship between the change in refractive index and polymerization-induced reduction in physical thickness during light-activated curing. This relationship between the optical and physical density demonstrates the potential of this technique as a unique noninvasive tool for measurement of the conversion degree of curing dental composite materials. PMID- 17343496 TI - Absorption of collagen: effects on the estimate of breast composition and related diagnostic implications. AB - The absorption spectrum of collagen powder is measured between 610 and 1040 nm by time-resolved transmittance spectroscopy. Absorption spectra of breast from healthy volunteers are then interpreted, adding collagen to the other absorbers previously considered (i.e., oxy- and deoxyhemoglobin, water, and lipids). A significant amount of collagen, depending on breast type, is estimated to be present. Adding collagen to the fitting procedure affects remarkably the estimated values of blood content and oxygenation. The quantification of collagen has potential implications for the assessment of breast density and cancer risk. PMID- 17343497 TI - In vivo optical characterization of human prostate tissue using near-infrared time-resolved spectroscopy. AB - The development of photodynamic therapy into a modality for treatment of prostate cancer calls for reliable optical dosimetry. We employ, for the first time, interstitial time-resolved spectroscopy to determine in vivo optical properties of human prostate tissue. Nine patients are included in the study, and measurements are conducted prior to primary brachytherapy treatment of prostate cancer. Intrasubject variability is examined by measuring across three tissue volumes within each prostate. The time-resolved instrumentation proves its usefulness by producing good signal levels in all measurements. We are able to present consistent values on reduced scattering coefficients (mu(s)'), absorption coefficients (mu(a)), and effective attenuation (mu(eff)) at the wavelengths 660, 786, and 916 nm. At 660 nm, mu(s)' is found to be 9+/-2 cm(-1), and mu(a) is 0.5+/-0.1 cm(-1). Derived values of mu(eff) are in the range of 3 to 4 cm(-1) at 660 nm, a result in good agreement with previously published steady state data. Total hemoglobin concentration (THC) and oxygen saturation are spectroscopically determined using derived absorption coefficients. Derived THC values are fairly variable (215+/-65 microM), while derived values of oxygen saturation are gathered around 75% (76+/-4%). Intrasubject variations in derived parameters correlate (qualitatively) with the heterogeneity exhibited in acquired ultrasound images. PMID- 17343498 TI - In vivo spectroscopic ellipsometry measurements on human skin. AB - We study the behavior of optical properties of human skin across its layers. We describe ellipsometric measurements for spectrally resolved in vivo investigations of biological tissue. We show in vivo measurements on human skin of the ellipsometric parameters Psi and Delta, which describe the change in polarization of light on reflection on a sample. A tape-stripping study reveals the depth profile of the ellipsometric parameters into the stratum corneum. The depth profile shows an increase in both quantities with increased depth. Analyzing the development of Psi on the number of strips using an exponential function shows a steady state after approximately 2 microm. The evolution of Psi and Delta can be described using a morphological model containing an effective medium approximation accounting for the water content of the skin, surface roughnesses of the corneocytes, as well as the alternating cell and lipid layers. PMID- 17343499 TI - Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range. AB - The optical parameters absorption coefficient, scattering coefficient, and the anisotropy factor of platelets (PLTs) suspended in plasma and cell-free blood plasma are determined by measuring the diffuse reflectance, total and diffuse transmission, and subsequently by inverse Monte Carlo simulation. Furthermore, the optical behavior of PLTs and red blood cells suspended in plasma are compared with those suspended in saline solution. Cell-free plasma shows a higher scattering coefficient and anisotropy factor than expected for Rayleigh scattering by plasma proteins. The scattering coefficient of PLTs increases linearly with the PLT concentration. The existence of physiological concentrations of leukocytes has no measurable influence on the absorption and scattering properties of whole blood. In summary, red blood cells predominate over the other blood components by two to three orders of magnitude with regard to absorption and effective scattering. However, substituting saline solution for plasma leads to a significant increase in the effective scattering coefficient and therefore should be taken into consideration. PMID- 17343500 TI - Optical properties of adenocarcinoma and squamous cell carcinoma of the gastroesophageal junction. AB - Photodynamic therapy (PDT) is an alternative to radical surgical resection for T1a or nonresectable carcinomas of the gastroesophageal junction. Besides the concentration of the photosensitizer, the light distribution in tissue is responsible for tumor destruction. For this reason, knowledge about the behavior of light in healthy and dysplastic tissue is of great interest for careful irradiation scheduling. The aim of this study is to determine the optical parameters (OP) of healthy and carcinomatous tissue of the gastroesophageal junction in vitro to provide reproducible parameters for optimal dosimetry when applying PDT. A total of 36 tissue samples [adenocarcinoma tissue (n=21), squamous cell tissue (n=15)] are obtained from patients with carcinomas of the gastroesophageal junction. The optical parameters are measured in 10-nm steps using new integrating sphere spectrometers in the PDT-relevant wavelength range of 300 to 1140 nm and evaluated by inverse Monte-Carlo simulation. Additional examinations are done in healthy tissue from the surgical safety margin. In the wavelength range of frequently applied photosensitizers at 330, 630, and 650 nm, the absorption coefficient in tumor tissue (adenocarcinoma 1.22, 0.16, and 0.15 mm(-1); squamous cell carcinoma 1.48, 0.13, and 0.11 mm(-1)) is significantly lower than in healthy tissue (stomach 3.34, 0.26, and 0.20 mm(-1); esophagus 2.47, 0.21, and 0.18 mm(-1)). The scattering coefficient of all tissues decreases continuously with increasing wavelength (adenocarcinoma 22.8, 12.99, and 12.52 mm(-1); squamous cell carcinoma 19.44, 9.35, and 8.98 mm(-1); stomach 20.55, 13.96, and 13.94 mm(-1); esophagus 20.34, 12.56, and 12.22 mm(-1). All tissues show an anisotropy factor between 0.80 and 0.94 over the entire spectrum. The maximum optical penetration depth for all tissues is achieved in the range of 800 to 1100 nm. At the wavelength range of 330, 630, and 650 nm, the optical penetration depth is significantly higher in carcinoma tissue (adenocarcinoma 0.27, 1.54, and 1.66 mm; squamous cell carcinoma 0.23, 1.71, and 1.84 mm) than in healthy tissue (stomach 0.16, 1.10, and 1.26 mm; esophagus 0.17, 1.47, and 1.65 mm; p<0.05). Above 1000 nm, a higher absorption coefficient of tumor tissue results in a lower optical penetration depth than in healthy tissue (p<0.05). The higher absorption and scattering of the tumor tissue in the wavelength range of available photosensitizer is associated with a low optical penetration depth. This necessitates higher energy doses and long application times or repeated applications to effectively treat large tumor volumes. Photosensitizers optimized for larger wavelength range need to be developed to increase the efficacy of PDT. PMID- 17343501 TI - Determination of the optical properties of anisotropic biological media using an isotropic diffusion model. AB - We investigate anisotropic light propagation in biological tissue in steady-state and time domains. Monte Carlo simulations performed for tissue that consists of aligned cylindrical and spherical scatterers show that steady-state and time resolved reflectance depends strongly on the measurement direction relative to the alignment of the cylinder axis. We examine the determination of optical properties using an isotropic diffusion model and find that in the time domain, in contrast to steady-state spatially resolved reflectance measurements, the obtained absorption coefficient does not depend on the measurement direction and is close to the true value. Contrarily, the derived reduced scattering coefficient depends strongly on the measurement direction in both domains. Measurements of the steady-state and time-resolved reflectance from bovine tendon confirm the theoretical findings. PMID- 17343502 TI - Boundary conditions in photoacoustic tomography and image reconstruction. AB - Recently, the field of photoacoustic tomography has experienced considerable growth. Although several commercially available pure optical imaging modalities, including confocal microscopy, two-photon microscopy, and optical coherence tomography, have been highly successful, none of these technologies can penetrate beyond approximately 1 mm into scattering biological tissues because all of them are based on ballistic and quasiballistic photons. Consequently, heretofore there has been a void in high-resolution optical imaging beyond this depth limit. Photoacoustic tomography has filled this void by combining high ultrasonic resolution and strong optical contrast in a single modality. However, it has been assumed in reconstruction of photoacoustic tomography until now that ultrasound propagates in a boundary-free infinite medium. We present the boundary conditions that must be considered in certain imaging configurations; the associated inverse solutions for image reconstruction are provided and validated by numerical simulation and experiment. Partial planar, cylindrical, and spherical detection configurations with a planar boundary are covered, where the boundary can be either hard or soft. Analogously to the method of images of sources, which is commonly used in forward problems, the ultrasonic detectors are imaged about the boundary to satisfy the boundary condition in the inverse problem. PMID- 17343503 TI - Optical pathology using oral tissue fluorescence spectra: classification by principal component analysis and k-means nearest neighbor analysis. AB - The spectral analysis and classification for discrimination of pulsed laser induced autofluorescence spectra of pathologically certified normal, premalignant, and malignant oral tissues recorded at a 325-nm excitation are carried out using MATLAB@R6-based principal component analysis (PCA) and k-means nearest neighbor (k-NN) analysis separately on the same set of spectral data. Six features such as mean, median, maximum intensity, energy, spectral residuals, and standard deviation are extracted from each spectrum of the 60 training samples (spectra) belonging to the normal, premalignant, and malignant groups and they are used to perform PCA on the reference database. Standard calibration models of normal, premalignant, and malignant samples are made using cluster analysis. We show that a feature vector of length 6 could be reduced to three components using the PCA technique. After performing PCA on the feature space, the first three principal component (PC) scores, which contain all the diagnostic information, are retained and the remaining scores containing only noise are discarded. The new feature space is thus constructed using three PC scores only and is used as input database for the k-NN classification. Using this transformed feature space, the centroids for normal, premalignant, and malignant samples are computed and the efficient classification for different classes of oral samples is achieved. A performance evaluation of k-NN classification results is made by calculating the statistical parameters specificity, sensitivity, and accuracy and they are found to be 100, 94.5, and 96.17%, respectively. PMID- 17343504 TI - Polarized light propagation in multiply scattering media exhibiting both linear birefringence and optical activity: Monte Carlo model and experimental methodology. AB - A Monte Carlo model for polarized light propagation in birefringent, optically active, multiply scattering media is developed in an effort to accurately represent the propagation of polarized light in biological tissue. The model employs the Jones N-matrix formalism to combine both linear birefringence and optical activity into a single effect that can be applied to photons as they propagate between scattering events. Polyacrylamide phantoms with strain-induced birefringence, sucrose-induced optical activity, and polystyrene microspheres as scattering particles are used for experimental validation. Measurements are made using a Stokes polarimeter that detects scattered light in different geometries, and compared to the results of Monte Carlo simulations run with similar parameters. The results show close agreement between the experimental measurements and Monte Carlo calculations for phantoms exhibiting turbidity and birefringence, as well as for phantoms exhibiting turbidity, birefringence, and optical activity. Other scattering-independent polarization properties can be incorporated into the developed Jones N-matrix formalism, enabling quantification of the polarization effects via an accurate polarization-sensitive Monte Carlo model. PMID- 17343505 TI - Perturbation and differential Monte Carlo methods for measurement of optical properties in a layered epithelial tissue model. AB - The use of perturbation and differential Monte Carlo (pMC/dMC) methods in conjunction with nonlinear optimization algorithms were proposed recently as a means to solve inverse photon migration problems in regionwise heterogeneous turbid media. We demonstrate the application of pMC/dMC methods for the recovery of optical properties in a two-layer extended epithelial tissue model from experimental measurements of spatially resolved diffuse reflectance. The results demonstrate that pMC/dMC methods provide a rapid and accurate approach to solve two-region inverse photon migration problems in the transport regime, that is, on spatial scales smaller than a transport mean free path and in media where optical scattering need not dominate absorption. The pMC/dMC approach is found to be effective over a broad range of absorption (50 to 400%) and scattering (70 to 130%) perturbations. The recovery of optical properties from spatially resolved diffuse reflectance measurements is examined for different sets of source detector separation. These results provide some guidance for the design of compact fiber-based probes to determine and isolate optical properties from both epithelial and stromal layers of superficial tissues. PMID- 17343506 TI - Experimental and model analysis on the temperature dynamics during diode laser welding of the cornea. AB - Corneal laser welding is a technique used clinically to induce the immediate sealing of corneal wounds. We present an experimental and model analysis of the temperature dynamics during diode laser-induced corneal welding, which is aimed at characterizing the mechanism of tissue fusion. Ex vivo tests were performed on porcine eyes in the typical irradiation conditions used for laser-induced suturing in cornea transplant. Three laser power densities (12.5 W/cm(2), 16.7 W/cm(2), 20.8 W/cm(2)) were tested. The superficial temperature of the cornea was measured by means of an infrared thermocamera. Experimental data were compared with the results of a three-dimensional (3D) model of a laser-welding process in the cornea, solved by the use of the Finite Element Method (FEM). The model solution and experimental results showed good agreement. The model was thus used to estimate the temperature enhancement inside the corneal wound and to calculate the thermal damage inside the tissue. The results indicated a selective, spatially confined heating effect that occurred at operative temperatures (59 to 66 degrees C) close to intermediate denaturation points of the stromal collagen, before its complete disorganization. No significant heat damage to the region of the laser-treated wound was evidenced in the operative irradiation conditions of corneal welding. PMID- 17343507 TI - Diffusion model for iontophoresis measured by laser-Doppler perfusion flowmetry, applied to normal and preeclamptic pregnancies. AB - We present a physical model to describe iontophoresis time recordings. The model is a combination of monodimensional material diffusion and decay, probably due to transport by blood flow. It has four adjustable parameters, the diffusion coefficient, the decay constant, the height of the response, and the shot saturation constant, a parameter representing the relative importance of subsequent shots (in case of saturation). We test the model with measurements of blood perfusion in the capillary bed of the fingers of women who recently had preeclampsia and in women with a history of normal pregnancy. From the fits to the measurements, we conclude that the model provides a useful physical description of the iontophoresis process. PMID- 17343509 TI - Characterization of flow direction in microchannels and zebrafish blood vessels by scanning fluorescence correlation spectroscopy. AB - The investigation of flow profiles in microstructures and tissues by fluorescence correlation spectroscopy (FCS) has been a challenging topic in the past decade. Due to its inherent optical configuration, a circular focused laser beam, FCS is unable to resolve microfluidic flow directions. Earlier schemes reported the use of two laser beams or the use of nonsymmetrical laser foci to break the symmetry of the measurement system. This, however, is difficult to combine with confocal systems since it would require modifications that interfere with the imaging capabilities. We propose a method called line-scan FCS to measure different flow angles in microchannels and tissues. This method is implemented on a combined laser scanning confocal microscopy (LSCM) and FCS system that enables uncompromised imaging and spectroscopy measurements. We demonstrate that by scanning the laser beam with a defined speed and direction we can measure flow direction with the current system at an optimal resolution of at least 3 microm. The combination system is assessed by measuring flow profiles in a microchannel with and without obstruction. To extend the technique to live tissue measurements we demonstrate that line-scan FCS can determine the flow direction in zebrafish small blood vessels in a label-free approach. PMID- 17343508 TI - Near-infrared spectroscopy measurement of the pulsatile component of cerebral blood flow and volume from arterial oscillations. AB - We describe a near-infrared spectroscopy (NIRS) method to noninvasively measure relative changes in the pulsate components of cerebral blood flow (pCBF) and volume (pCBV) from the shape of heartbeat oscillations. We present a model that is used and data to show the feasibility of the method. We use a continuous-wave NIRS system to measure the arterial oscillations originating in the brains of piglets. Changes in the animals' CBF are induced by adding CO(2) to the breathing gas. To study the influence of scalp on our measurements, comparative, invasive measurements are performed on one side of the head simultaneously with noninvasive measurements on the other side. We also did comparative measurements of CBF using a laser Doppler system to validate the results of our method. The results indicate that for sufficient source-detector separation, the signal contribution of the scalp is minimal and the measurements are representative of the cerebral hemodynamics. Moreover, good correlation between the results of the laser Doppler system and the NIRS system indicate that the presented method is capable of measuring relative changes in CBF. Preliminary results show the potential of this NIRS method to measure pCBF and pCBV relative changes in neonatal pigs. PMID- 17343510 TI - Detection of intramyocardial scroll waves using absorptive transillumination imaging. AB - Optical imaging using voltage-sensitive dyes has become an important tool for studying vortex-like electrical waves in the heart. Such waves, known as spiral or scroll waves, can spontaneously form in pathological ventricular myocardium, causing ventricular fibrillation and sudden death. Until recently, observations of scroll waves were limited to their surface manifestations, thus providing little information about the shape and location of their organizing center, the filament. We use computer modeling to assess the feasibility of visualizing filaments using dynamic transillumination imaging in conjunction with near-IR voltage-sensitive absorptive dyes (absorptive transillumination). We simulate transillumination signals produced by the intramural scroll waves in a realistic slab of ventricular tissue with trabeculated endocardial surface. The computations use a detailed ionic model of electrical excitation (LRd) coupled to a photon transport model for cardiac tissue. Our simulations show that dynamic absorptive transillumination data, with subsequent processing involving either amplitude maps, time-space plots, or power-of-the-dominant-frequency maps, can be used to reliably detect intramural scroll waves through the whole thickness (approximately 10 mm) of the ventricular wall. Neither variations in the thickness of the myocardial wall nor noise impeded the detection of intramural filaments. PMID- 17343511 TI - Snapshot hyperspectral imaging in ophthalmology. AB - Retinal imaging spectroscopy can provide functional maps using chromophore spectra. For example, oxygen saturation maps show ischemic areas from diabetes and venous occlusions. Obtaining retinal spatial-spectral data has been difficult due to saccades and long data acquisition times (>5 s). We present a snapshot imaging spectrometer with far-reaching applicability that acquires a complete spatial-spectral image cube in approximately 3 ms from 450 to 700 nm with 50 bands, eliminating motion artifacts and pixel misregistration. Current retinal spectral imaging approaches are incapable of true snapshot operation over a wide spectral range with a large number of spectral bands. Coupled to a fundus camera, the instrument returns true color retinal images for comparison to standard fundus images and for image validation while the patient is still dilated. Oxygen saturation maps were obtained with a three-wavelength algorithm: for healthy subjects arteries were approximately 95% and veins 30 to 35% less. The instrument is now undergoing clinical trials. PMID- 17343512 TI - Efficient compensation of Zernike modes and eye aberration patterns using low cost spatial light modulators. AB - Off-the-shelf spatial light modulators (SLMs) like those commonly included in video projection devices have been seldom used for the compensation of eye aberrations, mainly due to the relatively low dynamic range of the phase retardation that can be introduced at each pixel. They present, however, some interesting features, such as high spatial resolution, easy handling, wide availability, and low cost. We describe an efficient four-level phase encoding scheme that allows us to use conventional SLMs for compensating optical aberrations as those typically found in human eyes. Experimental results are obtained with artificial eyes aberrated by refractive phase plates introducing either single Zernike terms or complex eye aberration patterns. This proof-of concept is a step toward the use of low-cost, general purpose SLMs for the compensation of eye aberrations. PMID- 17343513 TI - Biochip reader with dynamic holographic excitation and hyperspectral fluorescence detection. AB - A highly parallel microarray scanner for functional genomic research using a dynamically reconfigurable holographic excitation and hyperspectral fluorescence detection is described. The light from two laser sources (405 and 532 nm) is split into an arbitrary number of focused spots on the biochip using a pair of spatial light modulators and a novel imaging system. The parallel optical scanner includes a hyperspectral detection unit with a high-sensitivity CCD camera to detect and analyze the emitted fluorescence spectra (from 430 to 800 nm) of all illuminated spots simultaneously. By using an xy scanner, the spectra of all spots on an entire array can be read out line by line. PMID- 17343514 TI - Design and quantitative resolution measurements of an optical virtual sectioning three-dimensional imaging technique for biomedical specimens, featuring two micrometer slicing resolution. AB - Several well-established techniques are available to obtain 3-D image information of biomedical specimens, each with their specific advantages and limitations. Orthogonal plane fluorescence optical sectioning (OPFOS), or selective plane illumination microscopy (SPIM), are additional techniques which, after adequate specimen preparation, produce high quality, autoaligned sectional images in nearly real time, of bone as well as soft tissue. Up until now, slicing resolutions down to 14 microm have been obtained. We present a high resolution (HR) OPFOS method, which delivers images that approach the quality of histological sections. With our HROPFOS technique, we achieve in-plane resolutions of 1 microm and a slicing resolution of 2 microm. A region of interest within an intact and much larger object can be imaged without problems, and as the optical technique is nondestructive, the object can be measured in any slicing direction. We present quantitative measurements of resolution. A 3-D model reconstructed from our HROPFOS data is compared to SEM results, and the technique is demonstrated with section images and 3-D reconstructions of middle ear specimens. PMID- 17343515 TI - Dual-wavelength microarray fluorescence detection system using volume holographic filter. AB - A dual-wavelength microarray scanner based on laser confocal principle is constructed to acquire the laser-induced two-color fluorescence from dyes Cy3 and Cy5. Unlike most commercially available micoarray scanners whose lasers are continuous wave, filters are bandpass and the channels are multiple photomultiplier tubes (PMTs), the system mainly consists of two diode lasers, four volume holographic band-stop filters, and one PMT. The central wavelengths of two kinds of volume holographic band-stop filters are equal to those of the two laser, respectively. The fluorescence beams can pass through the filters, while laser beams are blocked by them because the filters are cut off. The two fluorescences can pass through a common optical path. Thus, only one pinhole and one PMT are required. The two fluorescences are acquired by the PMT with time sharing. The two respective fluorescences can be gathered when two diode lasers work asynchronously. If lasers work synchronously, the two wavelength fluorescences could be acquired simultaneously by the same PMT. A synthesis of a two-color fluorescence image can be realized straightforwardly in this manner. An experiment is conducted and Cy3 and Cy5 fluorescences are captured. Gridding of the fluorescent images based on basic morphological erosion appropriately locates the boundary between adjacent spots. PMID- 17343517 TI - Mixed methods research is an effective method of enquiry for community health research. AB - Rapid social change, the pressure of contemporary living, an aging population and an increase in chronic disease have a significant impact on community health. The complex issues underlying research into community health offer significant challenges to the researcher. The use of mixed methods research is growing in popularity in a range of disciplines, although its application is less well understood. This paper will outline the utility of mixed methods research for community health research and demonstrate how this methodology can be used to enhance the richness of data obtained. PMID- 17343518 TI - The 'good' family syndrome: social and cultural issues in community and family health. PMID- 17343519 TI - Holding it all together: breast cancer and its impact on life for younger women. AB - While breast cancer is often associated with older women, in the year 2000, 25 % of new breast cancer diagnoses in Australia affected young women. An interpretive study using in-depth interviews provided valuable insight into the lived experiences of six young Queensland women living with breast cancer. This paper presents data from the study with a particular focus on young women and the impact it has on their social situation and their family. The young women in this study found a diagnosis of breast cancer traumatic and their responses were heightened as they sought to understand why at such a young age. For the younger woman a diagnosis of breast cancer is likely to cause not only emotional distress but concerns relating to motherhood, family and fertility. In many respects younger women having greater responsibility for the well being of others in their family and in the provision of stability for everyday family life face a tough reality than older women with breast cancer. This study identified that a specialist breast care nurse is an important resource. PMID- 17343520 TI - The role of Indigenous family ethnic schema on well-being among Native Hawaiian families. AB - Despite assertions of the importance of family in Indigenous cultures and its impact on psychological and physical health, there remains a paucity of research and a lack of measurement on Indigenous families' worldviews and their respective impact on well-being. The purpose of this investigation was to determine the relationship between Indigenous family ethnic schema and individual well-being. The sample consisted of 81 older adults (average age was 60.94 years old) with 77 Native Hawaiian and part-Native Hawaiian participants, and two Caucasian and two Asian participants with a Hawaiian partner or spouse. Family ethnic schema focusing on Indigenous values, beliefs, expectations and priorities was found to explain higher levels of individual well-being independent of age, income and gender. Clinical implications of family ethnic schema in terms of help-seeking behavior, treatment and adherence to treatment are discussed. PMID- 17343522 TI - Coronary heart disease in Asian Indians: perspectives of family members. AB - Despite the high prevalence rate and significant mortality and morbidity from coronary heart disease in Asian Indians (irrespective of their religious background), very few studies have reported on family members' experiences of caring for a person with coronary heart disease. This paper reports on family members' experiences of coronary heart disease in Asian Indians residing in Australia, and is part of a larger study that explored the experiences and/or understanding of coronary heart disease in Asian Indians from the perspective of patients, family members and 'healthy' participants. Using a constructivist approach semi-structured in-depth interviews were conducted with five family members. Findings are represented under the following main categories: 1. A period of complexity for family members; 2. Indian Culture: Its influence on health/health behaviour & illness experience; 3. Impact of migration and societal discrimination; 4. Disappointment with health care services and the health system; and 5. Strategies to prevent cardiac illness and attain optimal health. Cultural factors had both positive and negative influences not only on the illness experience but also on health behaviour and attitude. The impact of Indian culture in relation to coronary heart disease needs to be understood not only at the cultural level by providing culturally sensitive health care, but also by educating Asian Indians to change their health attitude and behaviour and improve their lifestyle. Asian Indians need education and advice to become more resilient and adaptable to a Western society and also to become aware of the acculturative effects of a Western lifestyle. PMID- 17343523 TI - Constructions of nutrition for community dwelling people with chronic disease. AB - The purpose of this paper is to explore the issue of nutrition as it relates to people who are living with chronic disease in the community. An examination of the health literature identifies the vulnerability of these people in relation to nutrition, and highlights the need for identifying and providing support to people who are at nutritional risk or undernourished. The aim of this study was to examine the meaning of nutrition for people living with chronic disease in the community, and to understand from the person's perspective the issues surrounding nutrition and how these issues are experienced. Data were generated with men and women learning to live with chronic conditions. Dialogue between participants and the researchers (first and second authors) were exchanged between 2003-2005 via email discussion groups. The findings of this paper reveal that an important aspect of providing support to people around nutrition issues is being overlooked. Participants contend that the biomedical approach with its emphasis on food intake and measurements, overlooks the person's unique historical and socio cultural meanings for food and eating. It is concluded that understanding these meanings are pivotal to creating a realistic and sustainable intervention plan that is meaningful and acceptable to the person. PMID- 17343524 TI - Community nursing in Brazil and child care in the family context. AB - This paper describes the critical elements that characterise current public policy on child and family care in Brazil and discusses the implications of these changes for the practice and teaching of child and family health nursing in Brazil. PMID- 17343525 TI - Parenting in public: 'watching the directives'. PMID- 17343526 TI - Chronic grief: experiences of working parents of children with chronic illness. AB - Parents of children with chronic illness experience multiple stressors associated with their numerous roles. For parents who are working full time and caring for a child with chronic illness, the stressors related to managing work and caring responsibilities are magnified. Although the impact of caring for a child with chronic illness has been widely investigated, the literature reveals a paucity of research on the experiences of parents who are also in full time employment. This paper shares qualitative findings of a study involving interviews of twelve parents who were working full time while caring for a child with chronic illness. Data was collected through in-depth semi structured interviews and thematic analysis was then used to develop and categorise themes. Two intertwined themes are reported: (1) grief and (2) dealing with professionals. In this study, parents revealed the chronic grief they experienced in relation to their child's condition, which often recurred at various stages of the child's illness. The child's initial diagnosis was found to be the most stressful part of the grieving process, with most feeling their voices as parents were not being heard or valued by health professionals at this time. This affected parents' confidence in the health care system and triggered the re-emergence of grief, aggravating an already stressful situation. The findings illustrate that the grief experienced by these parents can be exacerbated by their dealings with health professionals. Implications for various health professionals are drawn from the findings in order to highlight avenues where guidance and support can be provided to these parents. PMID- 17343527 TI - Mother/daughter intergenerational interviews: insights into qualitative interviewing. AB - As part of a larger study examining the social history of the Well Child/Health and Development Record Book in New Zealand, mother-daughter intergenerational dyad interviews were undertaken. The inter-generational dyad interviews were utilised to explore why mothers often keep their children's Well Child/Health and Development Record Books (Plunket Books) well beyond the five years of age that the Well Child Nurse stops visiting. Mother-daughter intergenerational dyad interviews are not a commonly used method of interview but can elicit valuable information that may otherwise be overlooked. This article discusses the method with which the interviews were undertaken and argues that successful construction of mother/daughter intergenerational dyad interviews is the result of a combination of context and the resulting interaction between the mother, daughter and interviewer/researcher. PMID- 17343528 TI - Disrupted relationships: adult daughters and father absence. AB - Changes in family structures have resulted in many children growing up in non traditional families, where their father is not resident in the family home. Father absence that occurs as a result of the breakdown of the parental relationship is associated with life adversity and less than optimal outcomes for children and adolescents. However, little research exists that explores this phenomenon from the perspective of the father absent young person. This phenomenological study was conducted in 2005 and aimed to explore women's perceptions about relationships with their fathers within the context of a father absent childhood. Nine women participated in this study. Findings revealed that growing up without their father present in the family home disrupted the relationship these daughters held with their fathers. Due to the perceived lack of interest these daughters felt from their fathers, they expressed feelings of hurt and diminished respect for their fathers. Furthermore, participants felt that their fathers were unable to provide them with the father-daughter relationship that they sought. The findings of this paper provide insights that can help nurses and other healthcare professionals to recognise the emotional impact that father absence can have on young women. Findings suggest a need for further research to gain greater insights into the experiences of family members who undergo disruption of relationships due to family breakdown. PMID- 17343529 TI - 'My Mom was my left arm': the lived experience of ableism for girls with Spina Bifida. AB - In many cultures, people deemed different, deficient or of lesser value are socially marginalized, disempowered, devalued and face innumerable barriers to health and quality of life. Persons deemed disabled are one such group. Through oppression, discrimination, and constant degradation, marginalized groups are denied the basic human right of dignity. For five girls with Spina Bifida, the experience of societal ableism, i.e. the belief that being able bodied is normal, eroded their sense of self worth, impinged upon their human rights, and isolated them in their own degradation - until they came together and spoke. My Mom Was My Left Arm illuminates the impact of ableism on the health and well-being of girls living with Spina Bifida. Several focus groups with five girls concerning their lives, anger and health yielded compelling reasons for today's contemporary nurse to explicitly practice from a social justice framework. In being deemed other, less than and viewed as their disability, the young women interviewed believed they had never reached their actual life potential. The relationship between health and ableist discrimination as lived by young women with Spina Bifida will be explored. The paper will close with nursing's ethical imperative to advocate for social justice, equity, fairness and dignity. PMID- 17343530 TI - How social myths about childhood, motherhood and medicine affect the detection of subtle developmental problems in young children. AB - Focus by child health professionals on the well-being of young Australian children and their families has intensified in the past decade, with particular attention drawn to the importance of the early detection and intervention of developmental problems. While many children with developmental difficulties are detected in the preschool years, those with more subtle forms of developmental problems are often only noticed by their mothers, passing unnoticed by professionals until the children begin school and fail socially or academically. This study aimed to ascertain ways in which child health professionals may utilise the experience of mothers to improve early recognition and diagnosis of subtle developmental and behavioural problems in children. French philosopher, Roland Barthes (1973) proposed that myths play an important social role in defining underlying social values that affect how people interpret what others say or do. This paper explores how the social myths of childhood, motherhood and medicine impact upon the early detection of children with subtle developmental problems. In particular, it examines how social myths affect when and how mothers become concerned about their children's development, from whom they seek advice, and the responses which mothers receive in regard to their concerns. Mythical notions of the 'blameless child', 'boys will be boys' and 'children who look OK are OK', and the constituted myth of motherhood, are all shown to affect when mothers become concerned about their children's development. What mothers do about their concerns and the responses they receive from child health professionals are also influenced by these myths. The myth of medicine is also examined to determine how it affects communication between mothers and doctors, the roles and responsibilities of doctors, and the value placed on a mother's concerns by doctors. PMID- 17343531 TI - Supporting parents and families: a critical, informed approach. PMID- 17343532 TI - Aunties & Uncles Co-operative Family Project Ltd: volunteers making a difference in the lives of children and parents. AB - This paper reports an evaluation of the Aunties and Uncles Co-operative Family Project Ltd, founded 30 years ago, that connects community volunteers (aunts and uncles) with disadvantaged children in the Sydney area, New South Wales, Australia. A postal survey was used which included both open and closed questions regarding the volunteer aunts, uncles, parents, coordinators, nieces and nephews' satisfaction with the project. Demographic data was also collected. Responses from the survey were statistically analysed using SPSS software. Responses to the open ended questions were transcribed and coded. The findings from the study indicated that the experiences were positive for all stakeholders with volunteers and coordinators finding the project personally rewarding and parents receiving respite and support. The children enjoyed new experiences by going to different places and undertaking activities. Recommendations include increased volunteer training and guidelines for difficult situations, increased support for coordinators and more structured activities for all participants. The findings indicate the reciprocal benefits to all participants. These significant benefits reflect the philosophy of the Aunties & Uncles Co-operative Family Project Ltd. PMID- 17343533 TI - Nursing practice in community child health: developing the nurse-client relationship. AB - Community nursing services to parents with young children have been an established part of child health services in Australia for more than a century. Although the titles vary within states, community child health nurses provide support services for parents with infants and young children and typically their scope of practice includes public health functions such as health surveillance of the developing infant and child up to the age of 5 years and early intervention. More recently state health policies have instituted universal home visiting and emphasized the primacy of psychosocial support for parents. These policies are accompanied by education programs that propose a change in nursing practice to a more egalitarian partnership model of practice. As a consequence greater attention now has to be paid to the processes used in developing a working relationship with the client in the community setting. Whilst there has been little published in the Australian nursing literature on the methods used by community child health nurses to engage their clients, the international literature offers some insights into the nurses' practice. This paper describes the practices of community child health nurses in engaging the parent and developing a complementary and therapeutic relationship that enables the nurse to promote the health of the child and family. Published accounts of community child health nursing practice in the United Kingdom, Scandinavia and northern America are described and compared to the Australian context. PMID- 17343534 TI - Working in partnership in the antenatal period: what do child and family health nurses do? AB - BACKGROUND: There is strong evidence that comprehensive sustained home visiting programs, commencing antenatally can improve child and maternal outcomes for vulnerable families. Community child and family health nurses, who traditionally engage with families post-birth, are well placed to provide interventions in the antenatal period. There is, however, little information on what home visiting nurses do, particularly in the antenatal period. An Australian trial of sustained nurse home visiting provides the opportunity to explore what child and family health nurses actually do in this new area of antenatal intervention. METHOD: Nurses completed a checklist following each home visit detailing the interventions undertaken. Descriptive analysis was undertaken to describe the frequency of each of interventions. Factor analysis was undertaken to group the interventions into clusters. Further analysis was undertaken to determine if the clusters of interventions were associated with the frequency of home visits or characteristics of the mothers/families. RESULT: Four clusters of interventions were identified: comprehensive range of physical and psychosocial care for most families; ongoing management of lower risk needs for mothers who were young, unsupported or had a history of mental health problems; preventive care for first time mothers; and management of high risk needs (drugs and alcohol and domestic violence) in conjunction with other professionals. DISCUSSION AND CONCLUSION: The interventions undertaken reflect the conceptual framework of the program. Nurses are delivering a comprehensive range of physical and psychosocial care to most women and families in the antenatal period, with some groups of women receiving additional support related to differing areas of needs. PMID- 17343535 TI - Fractured families: parental perspectives of the effects of adolescent drug abuse on family life. AB - Drug use in young people has serious ramifications for health and well-being of young people and their families and continues to be an area of major concern for health workers. Though the task of dealing with drug-related problems falls on families, particularly parents, very little literature has explored parental experiences of managing drug use within the context of family life. Eighteen parents of drug-abusing young people were recruited into this qualitative study that aimed to develop understandings into the effects of adolescent drug use on family life. Findings revealed that the experience of having a drug-abusing adolescent family member had a profound effect on other members of the immediate family. Family relationships were fractured and split as a result of the on-going destructive and damaging behaviour of the drug-abusing young person. Five themes were identified that captured the concept of fractured families. These are: betrayal and loss of trust: 'You had to have the doors locked'; abuse, threats and violence: 'there were holes in the wall'; sibling anger and resentment: 'Better off now with him gone'; isolated, disgraced and humiliated: 'You are on your own with it'; and, feeling blamed: 'You are not a good parent'. Implications for practice and further research are drawn from the findings of this paper. PMID- 17343536 TI - Using patterns of knowing in nursing as a possible framework for nursing care of homeless families with children. AB - In developed countries such as Australia, the United Kingdom and the United States of America, homeless families are amongst the fastest growing subpopulations of the homeless. This paper seeks to explore the major issues involved in the health and nursing care of such families, and proposes that the patterns of knowing in nursing offer a pertinent, guiding framework for nurses to understand the phenomenon and to optimize holistic nursing care for homeless families with children. PMID- 17343537 TI - Adolescent health: we have a long way to go. PMID- 17343541 TI - The relationship between periodontal disease, bacterial vaginosis, and preterm birth. AB - Spontaneous preterm labor leading to preterm birth is a major cause of perinatal mortality and morbidity worldwide. The etiology of spontaneous preterm labor is multifactoral but there is overwhelming evidence to implicate infection in up to 40% of cases. Historically, this infective link has focused on the associations between abnormal genital tract flora in pregnancy (diagnosed by the presence of bacterial vaginosis) and preterm birth. Recently, another condition related to abnormal flora (periodontal disease) has been linked with preterm birth. There are microbiological similarities between the oral cavity and the female genital tract giving rise to a possible common pathophysiology. This review records the interrelationship between periodontal disease, bacterial vaginosis, and preterm birth. We postulate on the mechanism linking the three conditions, particularly through microbiology and gene-environmental interactions. Periodontal disease and bacterial vaginosis may be risk factors in their own rights or may be interrelated. We speculate on whether periodontitisis a marker for an immune hyperresponse to abnormal flora which in the oral cavity results in periodontitis and in the case of bacterial vaginosis might result in preterm birth. We also postulate on the risk of preterm birth by periodontitis alone, bacterial vaginosis alone, or both. PMID- 17343542 TI - Uteroplacental circulation, preeclampsia, and maternal abdominal aortic stiffness in normal and compromised pregnancies. AB - A study of 82 normal and 60 compromised pregnant women who were identified by uterine artery Doppler flow waveform systolic/diastolic ratio >95th percentile (increased peripheral resistance) was carried out to examine the elastic properties of the maternal abdominal aorta (AA). An aortic stiffness index (SI) was measured between 18 and 40 weeks at four-weekly intervals with a phase-locked loop ultrasound technique to estimate the aortic systolic and diastolic diameters and their correlation with blood pressure. In the normal group, the aortic systolic and diastolic diameters, as well as the SI, increased with the maternal age. In the compromised group, aortic diameter and blood pressure were normal, but the SI during the early second trimester was increased. Twenty-two women from the compromised group with an SI above the 95th percentile for their age had a significantly higher prevalence of preeclampsia in comparison with women with a normal SI (P<0.001). The aortic SI was significantly higher in severe than in mild preeclampsia. This study demonstrates that stiffness of the AA is increased in pregnant women with preeclampsia and that a progressive increase of the SI in serial studies is associated with severity of the disease. Aberrant hemodynamic adaptation in preeclampsia seems to include increased stiffness of the larger artery besides high resistance in small peripheral arteries. PMID- 17343543 TI - Induction of labor with oral misoprostol for premature rupture of membranes at term in women with unfavorable cervix: a randomized, double-blind, placebo controlled trial. AB - AIM: To evaluate the efficacy and safety of oral misoprostol for labor induction in women with term premature rupture of membranes (PROM) and an unfavorable cervix. METHODS: We randomized 130 women with PROM of < or =4 h to either oral misoprostol, 50 microg, or a placebo given every 4 h for up to three doses. Intravenous oxytocin was initiated if active labor did not begin within 12 h. RESULTS: Sixty-four women received oral misoprostol and 66 received placebo. The PROM-to-delivery interval was shorter with misoprostol than with placebo (13.7+/ 5.8 vs. 20.3+/-6.8 h, respectively, P<0.05). Misoprostol significantly reduced the need for oxytocin (28.1 vs. 72.7%, P<0.001) and antibiotics (25 vs. 69.7%, P<0.001). No significant differences in cesarean section or hyperstimulation rate were noted. CONCLUSION: Oral misoprostol given to women with unfavorable cervix soon after term PROM significantly reduces the induction-to-delivery time and the need for oxytocin and antibiotics. PMID- 17343544 TI - The combined effect of betamethasone and ritodrine on the middle cerebral artery in low risk third trimester pregnancies. AB - AIMS: To evaluate the effect of antenatal betamethasone and ritodrine in third trimester low risk singleton pregnancies by Doppler technology. SUBJECTS AND METHODS: Eighty-four third trimester pregnant women who received a full course of betamethasone and delivering uneventfully were recruited. The Doppler examination included the assessment of the pulsatility index (PI) of the umbilical artery (UA PI) and the middle cerebral artery (MCA PI) prior to treatment (baseline), and 48, 72 and 96 h after the second dose of betamethasone. RESULTS: No significant difference was found in UA PI and UA/MCA values following betamethasone therapy. In contrast, MCA PI decreased significantly 48 h from the last injection of betamethasone in the whole study group (P<0.001), and returned to basal values at 96 h. We also found that MCA PI was reduced significantly at 48 h in the subgroup under tocolysis (n=41) and in the subgroup not receiving tocolysis (n=43). We compared MCA PI values for both subgroups in the four timings, and found a non significant difference comparing baseline and 96 h values. However, when comparing MCA PI values after 48 and 72 h, significantly lower differences in PI values in both subgroups were found. CONCLUSION: In low risk pregnancies, betamethasone therapy in the third trimester is related to a significant but transient reduction of MCA PI, which is more pronounced during tocolytic therapy. Although the physiological basis of this effect is currently unclear, it could be related to the local regulation of intracerebral blood flow. PMID- 17343545 TI - Detection rate of Helicobacter pylori stool antigen in newborn infants and small children. AB - AIMS: To investigate the prevalence of H. pylori antigen in the stools of Norwegian neonates and small children. METHODS: A total of 249 children aged 0 days-3 years were tested for the presence of H. pylori antigen in feces using the HpSA immunoassay. For verification purposes, a selection of samples were analyzed with PCR targeting the 16 S rDNA Helicobacter gene. RESULTS: H. pylori antigen in stool was detected in 52% (36/69) of the neonates, in 15% (7/46) of infants aged 7 days-1 month, and in 5% (7/134) of children aged 1 month-3 years. In neonates, H. pylori antigen detection was significantly associated with mode of delivery: 59% (30/51) with uncomplicated vaginal births were HpSA positive compared to only 10% (1/10) of infants delivered by cesarean section (P=0.02). Positive PCR results were found in 35% (9/26) of HpSA positive samples. Sequencing of PCR products revealed 97-100% homology with gene sequences from both H. pylori and other Helicobacter species. CONCLUSIONS: The low H. pylori antigen detection rate in children >1 month of age is in accordance with previous prevalence studies from Western countries. The unexpected finding of a high H. pylori antigen detection rate in neonates suggests that transient colonization may occur in the neonatal period. PMID- 17343546 TI - Spontaneous twin pregnancy in a 56-year-old primipara. PMID- 17343549 TI - A 26-week open-label study of quetiapine in children with conduct disorder. AB - OBJECTIVE: The aim of this study was to describe the long-term safety and effectiveness of quetiapine in conduct disorder (CD). METHODS: This was an 18 week outpatient follow-up study of an acute trial that enrolled aggressive children ages 6-12 years with a primary diagnosis of CD. To be enrolled into this study, subjects had to have successfully completed participation in the initial 8 week, open-label, outpatient quetiapine trial. Psychometric measures included the Rating of Aggression Against People and/or Property Scale (RAAPP), the Nisonger Child Behavior Rating Form (NCBRF), the Conners' Parent Rating Scale (CPRS-48), the Clinical Global Impressions Scale of Severity (CGI-S), and the Children's Global Assessment Scale. RESULTS: Nine males with a mean age of 8.9 (SD = 1.2) years were treated. The median quetiapine dose at end of study was 150 mg/day (range 75-350). Mean psychometric scores did not change substantively from baseline. No patients experienced extrapyramidal side effects. Three subjects discontinued due to study nonadherence. No patients discontinued treatment due to an adverse event. CONCLUSIONS: These preliminary data suggest that quetiapine might be a generally safe and effective maintenance treatment for aggressive children with CD who initially respond to an acute therapeutic trial of quetiapine. More research is needed to confirm or refute these initial findings. PMID- 17343550 TI - Striatal creatine and glutamate/glutamine in attention-deficit/hyperactivity disorder. AB - OBJECTIVE: The glutamatergic prefrontal-striatal pathway has been implicated previously in the neurobiology of attention-deficit/hyperactivity disorder (ADHD). We used short echo proton magnetic resonance spectroscopy (1H-MRS) to examine glutamate in the prefrontal cortex, left striatum, and, as a control area, the occipital lobe. METHOD: Thirteen treatment-naive ADHD children and 10 healthy comparison subjects participated. All were males between the ages of 6 to 11 years of age. Twelve ADHD subjects were scanned after 8 weeks of treatment. RESULTS: Striatal glutamate, glutamate/glutamine (Glx) and creatine concentrations were greater in the ADHD subjects at baseline as compared to controls. Only striatal creatine, not glutamate or Glx, was reduced after stimulant treatment in the ADHD patients. No significant differences between groups were noted in the remainder of the striatal metabolites or any of the occipital lobe or prefrontal cortex metabolites. CONCLUSIONS: These findings provide initial evidence of a striatal creatine/glutamatergic dysregulation in ADHD. PMID- 17343551 TI - A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention deficit/hyperactivity disorder combined type. AB - BACKGROUND: Disturbances in N-methyl-D-aspartate (NMDA) receptor activity may play a role in attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: This study is a preliminary evaluation of the safety, pharmacokinetics, and effectiveness of the NMDA receptor antagonist memantine in pediatric ADHD. METHODS: An open-label, dose-finding, 8-week, trial in outpatients 6-12 years old with ADHD combined type. Memantine oral solution (2 mg/mL) was titrated to 10 mg/day (n = 8) or 20 mg/day (n = 8). Safety data and blood samples for pharmacokinetic analyses were collected. The ADHD Rating Scale-IV (ADHD-IV) and Clinical Global Impression of Severity (CGI-S) scale measured the effectiveness of memantine. RESULTS: There were no discontinuations due to adverse events (AEs), serious AEs, deaths, or suicides. Most AEs were mild and occurred during the first week of treatment. The 20 mg/day memantine dose was associated with a higher rate of completion and larger mean improvement on the ADHD-IV and CGI-S than 10 mg/day memantine. Pharmacokinetic analyses suggest response to memantine may be dose-dependent beyond an initial threshold concentration. CONCLUSIONS: This pilot study suggests that a memantine dose of 20 mg/day may be a safe and possibly effective treatment for pediatric ADHD. Further investigations of memantine in ADHD appear to be warranted. PMID- 17343552 TI - Preliminary evidence of beneficial effects of methylphenidate on listening comprehension in children with attention-deficit/hyperactivity disorder. AB - OBJECTIVE: The effect of methylphenidate (MPH) on listening comprehension for information passages, and on working memory, was examined in a clinical sample of 16 children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Drug effects on comprehension of spoken language at the levels of single sentences and passages, and on verbal and visual-spatial working memory (WM) skills were assessed over a 4-day placebo-controlled, double-blind, crossover treatment trial of MPH at low, medium, and high doses. Concurrent behavior ratings were also completed. Data were analyzed at both group and individual levels; individual improvements using average change scores were analyzed to explore interrelationships among comprehension, WM, and behavioral responses to MPH. RESULTS: There was a significant effect of drug on comprehension of inferences from challenging listening passages (F = 3.1, p ,0.05), and on visual-spatial working memory performance (F = 3.3, p ,0.05), with significant linear dose response relationships evident for both domains. Individual improvements in comprehension using averaged placebo-dose change scores were not related to improvements in behavior with MPH, or to improvements in WM in this sample. CONCLUSIONS: Findings provide preliminary evidence that MPH affects higher-level language comprehension skills, which require sustained attention and mental effort. If generalizable to classroom listening skills, these findings have implications for clinicians and teachers involved with children with ADHD. PMID- 17343553 TI - Emotional expression during attention-deficit/hyperactivity disorders treatment: initial assessment of treatment effects. AB - OBJECTIVE: The purpose of this research was to provide an initial examination of the effects of atomoxetine and stimulants on emotional expression using a newly developed scale for assessing emotional expression in children with attention deficit/hyperactivity disorder (ADHD). METHOD: The parent-rated Expression and Emotion Scale for Children (EESC) was collected during two studies. During a cross-sectional validation study, the EESC was completed to assess the child's current treatment and retrospectively for previous medication. In a randomized, placebo-controlled trial of atomoxetine, the EESC was collected at baseline and endpoint. RESULTS: In the validation study, no statistically significant differences in EESC scores were found between groups taking atomoxetine (n = 74) and stimulants (n = 105). Patients who switched from a stimulant to atomoxetine (n = 40) had greater improvement in emotional expression than those switched to another stimulant (n = 21) (p = 0.008). In the clinical trial, no difference in rates of worsening of emotional expression were observed (atomoxetine 8.8%, placebo 12.3%; p = 0.440). CONCLUSION: No treatment differences in emotional expression were observed based on current medications. However, stimulant patients needing to switch medications may have greater improvements in emotional expression by switching to atomoxetine. PMID- 17343554 TI - Measurement of the subjective effects of methylphenidate in 11- to 15-year-old children with attention-deficit/hyperactivity disorder. AB - OBJECTIVE: This study examined subjective and other behavioral effects of methylphenidate (MPH) among adolescents. METHODS: Standard abuse liability assessment methods that have been used in adult populations were modified for attention-deficit/hyperactivity disorder (ADHD) adolescents. MPH effects (0, 0.25 mg/kg) were evaluated under randomized, double-blind conditions in two 5-hour laboratory sessions in 24 (13 female) 11-15 year olds diagnosed with ADHD. RESULTS: Repeated measures analysis of covariance indicated significant dose and dose by time interactions on subjective ratings on the modified amphetamine (A) [F (1, 20) = 5.98; p < 0.05; eta2 = 0.36], morphine-benzedrine group (MBG) [F (1, 21) = 8.93 p < 0.01; eta2 = 0.38] and benzedrine group scale (BG) [F (1, 21) + 13.10 p < 0.01; eta2 = 0.37] scales of the Addiction Research Center Inventory; "Hungry" and "How sure are you that you got the medication today?" from the Visual Analogue Scale, the Profile of Mood States Depression scale, performance on the Continuous Performance Task, heart rate and blood pressure, and level of activity. CONCLUSIONS: This is the first study to document subjective effects of stimulants in adolescents with ADHD that have been associated with drug abuse potential in adults. There are increasing concerns about nontherapeutic stimulant use in adolescents and young adults. Assessing subjective effects of pharmacotherapies for ADHD along with other measures of abuse potential such as drug self-administration may aid in assessing the therapeutic effects and/or risk of medications used in the treatment of ADHD. PMID- 17343555 TI - Choosing an attention-deficit/hyperactivity disorder rating scale: is item randomization necessary? AB - OBJECTIVE: Although behavior rating scales are generally considered de riguer for best clinical practices in the diagnosis and medical management of children with attention-deficit/hyperactivity disorder (ADHD), they are often time consuming to score, especially if items are arranged in random order. This study compares two methods of ordering rating scale items; namely, diagnostic-cluster versus randomized-order formats. METHODS: Participants were the parents of 207 consecutive referrals (5-17 years) to a child psychiatry outpatient service who were diagnosed as having a variety of emotional and behavioral disorders. Children were assessed with a battery of standardized assessment instruments and clinical interviews, including the ADHD Symptom Checklist-4. Half completed a diagnostic-cluster version and half completed a randomized-order version. RESULTS: Findings indicated that the internal consistency reliability, clinical utility (for identifying children with ADHD and oppositional defiant disorder), and concurrent validity of the two-item arrangement formats were virtually identical. CONCLUSION: Item arrangement does not appear to impact the reliability or validity of a commonly used ADHD rating scale. PMID- 17343556 TI - Age onset subtypes of obsessive compulsive disorder: differences in clinical response to treatment with clomipramine. AB - An open-label, 8-week, follow-up study was designed to compare subjects with child versus adult onset of obsessive compulsive disorder (OCD) on their clinical characteristics and response to a standardized treatment with clomipramine. The study included 15 children and 13 adults with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of OCD. Children received 50 225 mg/day (3-5 mg/kg day) and adults 150-250 mg/ day of clomipramine. The children's group had a higher number of males and increased comorbidity than the adults' group. A similar dose/kg day of clomipramine was effective in reducing OCD severity and improving the psychosocial functioning in both groups; however, total improvement according to the National Institute of Mental Health-Global Obsessive Compulsive Rating Scale (NIMH-GOCRS) was greater in adults. Adults reported a higher frequency of side effects compared to children, with dry mouth and constipation more common at the end of the study. These data suggest that children with OCD seeking treatment may have differences from adults and support the importance of studying age-of-onset subtypes of OCD. PMID- 17343557 TI - Health-related quality of life in adolescents with bipolar I disorder. AB - OBJECTIVE: To examine abnormalities in health-related quality of life (HRQOL) and to determine whether pharmacological intervention with divalproex or quetiapine alters HRQOL abnormalities in bipolar adolescents. METHOD: Parents of 23 adolescents diagnosed with a manic or mixed episode associated with bipolar I disorder were asked to rate their child's health using the Child Health Questionnaire-Parental Form 50 (CHQ-PF 50) at baseline, prior to receiving medication and then at 28 days later. RESULTS: Manic adolescents exhibited significantly worse HRQOL than national norms at baseline on all subscales of the CHQ-P50 except for those assessing physical well-being. Twenty eight days later, similar results were obtained for the divalproex group. Significant improvements in HRQOL, particularly on the psychosocial subscales, occurred for both groups. CONCLUSIONS: HRQOL for bipolar youth improves following pharmacological treatments. However, distinct effects of specific treatments may exist, and impairment in several domains persists. PMID- 17343558 TI - Manic symptoms and behavioral dysregulation in youth with velocardiofacial syndrome (22q11.2 deletion syndrome). AB - Mania and bipolar disorder have been reported in adolescents and adults with velocardiofacial syndrome (VCFS; also known as 22q11.2 deletion syndrome). Children with VCFS have a high prevalence of attention-deficit/hyperactivity disorder (ADHD), which may constitute a risk factor for the eventual development of bipolar disorder in this population. Therefore, we sought to determine whether children with VCFS exhibit more manic symptoms than community controls that also may have learning disorders and ADHD. The study population consisted of 86 children with VCFS and 36 community controls from ages 9 to 15 years, using measures of Young Mania Rating Scale-Parent Version, Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), Child Behavior Checklist (CBCL), and Wechsler Intelligence Scale for Children-3rd edition (WISC-III). The results indicate that manic symptoms were not more prevalent in VCFS than in a community sample of children with learning disorders and ADHD. However, after accounting for symptoms of depression and ADHD, we found that manic symptoms in VCFS predicted uniquely to scores on four Child Behavior Checklist (CBCL) subscales, including anxiety, somatization, thought, and conduct problems. In contrast, manic symptoms in controls predicted uniquely to conduct problems only. Accordingly, our findings of severe behavioral impairment in youth with VCFS and manic symptoms suggest that these children may warrant more intensive monitoring and treatment relative to youth with VCFS and ADHD only. PMID- 17343560 TI - Duloxetine treatment of pediatric chronic pain and co-morbid major depressive disorder. AB - In the United States, the novel compound duloxetine has been approved for the treatment of major depressive disorder (MDD) and diabetic peripheral neuropathic pain in the adult population. There are currently no published data on the use of duloxetine in children and adolescents. This report describes the successful treatment of 2 adolescent females with chronic pain and co-morbid MDD. Both patients required admission to a tertiary-care pediatric hospital due to the chronicity, severity, and treatment resistance of their pain syndromes. In both cases, duloxetine provided rapid improvement in the experience of pain, as well as mood symptoms, at minimum dosages. Pain symptom reduction and restoration of a euthymic state was maintained at 4- and 3-month follow-up visits, respectively, with minimal to no adverse effects being reported. These cases present preliminary evidence of promising uses for duloxetine in the pediatric population. PMID- 17343559 TI - Metyrosine in psychosis associated with 22q11.2 deletion syndrome: case report. AB - This report describes the use of metyrosine (Demser) in an adolescent male with psychosis associated with the 22q11.2 deletion syndrome (velocardiofacial syndrome; VCFS), diagnosed by fluorescence in situ hybridization (FISH). He presented with multiple features of 22q11.2 deletion syndrome, including ventricular septal defect, palatal abnormalities, speech and motor delays, attention deficits, mood lability, and psychosis. After a failed trial of an atypical antipsychotic to address the psychosis, metyrosine was initiated, with significant reduction of psychotic symptoms and mood lability. Metyrosine treatment allowed this youth to live at home and to attend school, after months of recurrent psychiatric hospitalizations. The successful treatment of metyrosine for psychosis associated with VCFS represents a first in psychiatry, where a known biochemical abnormality in a psychiatric disorder was corrected by a treatment that targets the biochemical pathway, leading to reduction of psychiatric symptoms and improvement of functioning. PMID- 17343561 TI - Topiramate in adolescents with juvenile bipolar disorder presenting weight gain due to atypical antipsychotics or mood stabilizers: an open clinical trial. AB - BACKGROUND: Many children and adolescents with bipolar disorder (BD) do not adhere to the pharmacological treatment due to weight gain. This investigation aims to describe response, side effects, and weight changes in a sample of youths with BPD while receiving topiramate for 11 weeks during the treatment maintenance phase. METHODS: Ten consecutive outpatients with BPD (11-17 years) using a single mood stabilizer and/or an antipsychotic presenting weight gain over 5% of their baseline weight were enrolled in this 11-week protocol. Their medication was switched to topiramate during the first 4 weeks. The Young Mania Rating Scale (Y MRS) was the main outcome measure to assess response to the treatment in a weekly basis. Side effects and weight were also assessed weekly. RESULTS: In repeated measure analysis of variance (ANOVA), we found a significant reduction in both the YMRS scores (F = 10.21; p ,0.01) and in weight (F = 8.04; p ,0.01) during the trial. CONCLUSIONS: These initial findings suggesting antimanic effects for topiramate during the treatment maintenance phase associated with weight reductions indicate the need of randomized clinical trials assessing this clinical relevant issue. PMID- 17343563 TI - Trichotillomania and co-morbid psychiatric disorders in a 10-year-old boy. PMID- 17343564 TI - Consumer-directed health care: not quite the cure yet. PMID- 17343565 TI - Oral candidiasis secondary to adverse anticholinergic effects of psychotropic medications. PMID- 17343566 TI - Comparative analysis of adeno-associated viral vector serotypes 1, 2, 5, 7, and 8 in mouse brain. AB - Recombinant adeno-associated virus serotype 2 (rAAV2) vectors have been shown to deliver genes effectively to neurons in the brain, retina, and spinal cord. The characterization of new AAV serotypes revealed different patterns of transduction in a diverse array of tissues (Gao, G., Vandenberghe, L.H., and Wilson, J.M. [2005]. Curr. Gene Ther. 5, 285-297). Here, we extensively compare the neural tropism of human-derived rAAVs (types 2/1, 2, and 2/5) with nonhuman primate derived rAAVs (types 2/7 and 2/8) in adult mouse brain. Mice were injected with rAAV type 2/1, 2, 2/5, 2/7, or 2/8 via the caudate-putamen and substantia nigra. Intrahippocampal injections were also performed for rAAV2/7 and rAAV2/8. In all regions injected, the vectors transduced neurons almost exclusively. Retrograde transduction of all rAAV pseudotypes was also observed in particular CNS areas. At high titers, all rAAV pseudotypes transduced comparable brain volumes in all targeted regions except for rAAV2, which transduced much smaller brain volumes. A dose-range comparison of intrastriatally injected rAAV types 2/5, 2/7, and 2/8 highlighted that the transduction efficiency, as determined by transduced volume and biophotonic imaging of green fluorescent protein expression intensity, was significantly higher for rAAV2/5 and rAAV2/7 compared with rAAV2/8 at low titers, whereas all three serotypes performed equally well at higher doses. These results demonstrate the use and efficiency of both human- and nonhuman primate-derived rAAV vectors for disease modeling and their potential for gene therapy. PMID- 17343567 TI - The reductase NCB5OR is responsive to the redox status in beta-cells and is not involved in the ER stress response. AB - The novel reductase NCB5OR (NADPH cytochrome b5 oxidoreductase) resides in the ER (endoplasmic reticulum) and may protect cells against ER stress. Levels of BiP (immunoglobulin heavy-chain-binding protein), CHOP (CCAAT/enhancer-binding protein homologous protein) and XBP-1 (X-box-binding protein-1) did not differ in WT (wild-type) and KO (Ncb5or-null) tissues or MEFs (mouse embryonic fibroblasts), and XBP-1 remained unspliced. MEFs treated with inducers of ER stress demonstrated no change in Ncb5or expression and expression of ER-stress induced genes was not enhanced. Induction of ER stress in beta-cell lines did not change Ncb5or expression or promoter activity. Transfection with Ncb5or-specific siRNA (small interfering RNA) yielded similar results. Microarray analysis of mRNA from islets and liver of WT and KO animals revealed no significant changes in ER-stress-response genes. Induction of oxidative stress in betaTC3 cells did not alter Ncb5or mRNA levels or promoter activity. However, KO islets were more sensitive to streptozotocin when compared with WT islets. MEFs incubated with nitric oxide donors showed no difference in cell viability or levels of nitrite produced. No significant differences in mRNA expression of antioxidant enzymes were observed when comparing WT and KO tissues; however, microarray analysis of islets indicated slightly enhanced expression of some antioxidant enzymes in the KO islets. Short-term tBHQ (t-butylhydroquinone) treatment increased Ncb5or promoter activity, although longer incubation times yielded a dose-dependent decrease in activity. This response appears to be due to a consensus ARE (antioxidant-response element) present in the Ncb5or promoter. In summary, NCB5OR does not appear to be involved in ER stress, although it may be involved in maintaining or regulating the redox status in beta-cells. PMID- 17343568 TI - Catalytic mechanism of Zn2+-dependent polyol dehydrogenases: kinetic comparison of sheep liver sorbitol dehydrogenase with wild-type and Glu154-->Cys forms of yeast xylitol dehydrogenase. AB - Co-ordination of catalytic Zn2+ in sorbitol/xylitol dehydrogenases of the medium chain dehydrogenase/reductase superfamily involves direct or water-mediated interactions from a glutamic acid residue, which substitutes a homologous cysteine ligand in alcohol dehydrogenases of the yeast and liver type. Glu154 of xylitol dehydrogenase from the yeast Galactocandida mastotermitis (termed GmXDH) was mutated to a cysteine residue (E154C) to revert this replacement. In spite of their variable Zn2+ content (0.10-0.40 atom/subunit), purified preparations of E154C exhibited a constant catalytic Zn2+ centre activity (kcat) of 1.19+/-0.03 s(-1) and did not require exogenous Zn2+ for activity or stability. E154C retained 0.019+/-0.003% and 0.74+/-0.03% of wild-type catalytic efficiency (kcat/K(sorbitol)=7800+/-700 M(-1) x s(-1)) and kcat (=161+/-4 s(-1)) for NAD+ dependent oxidation of sorbitol at 25 degrees C respectively. The pH profile of kcat/K(sorbitol) for E154C decreased below an apparent pK of 9.1+/-0.3, reflecting a shift in pK by about +1.7-1.9 pH units compared with the corresponding pH profiles for GmXDH and sheep liver sorbitol dehydrogenase (termed slSDH). The difference in pK for profiles determined in 1H2O and 2H2O solvent was similar and unusually small for all three enzymes (approximately +0.2 log units), suggesting that the observed pK in the binary enzyme-NAD+ complexes could be due to Zn2+-bound water. Under conditions eliminating their different pH dependences, wild-type and mutant GmXDH displayed similar primary and solvent deuterium kinetic isotope effects of 1.7+/-0.2 (E154C, 1.7+/-0.1) and 1.9+/-0.3 (E154C, 2.4+/-0.2) on kcat/K(sorbitol) respectively. Transient kinetic studies of NAD+ reduction and proton release during sorbitol oxidation by slSDH at pH 8.2 show that two protons are lost with a rate constant of 687+/-12 s(-1) in the pre steady state, which features a turnover of 0.9+/-0.1 enzyme equivalents as NADH was produced with a rate constant of 409+/-3 s(-1). The results support an auxiliary participation of Glu154 in catalysis, and possible mechanisms of proton transfer in sorbitol/xylitol dehydrogenases are discussed. PMID- 17343569 TI - Utility of sentinel node biopsy in vulvar and vaginal melanoma: report of two cases and review of the literature. AB - Sentinel node (SN) biopsy is widely applied for treatment planning of cutaneous melanoma. However, using this strategy in female lower genital tract tumors has not yet been established. We report two cases, one each of vulvar and vaginal melanoma who underwent SN biopsy and review the available literature. Our experience and available limited evidence suggests that this low morbidity technique can be used for obtaining prognostic information and hence treatment planning for this disease. However, a false negative rate perhaps in the order of 15% suggests that careful consideration is necessary before using sentinel lymph node biopsy in the management of vulvar and vaginal melanoma. PMID- 17343570 TI - Mutation analysis of the tumor suppressor gene PPP2R1B in human cervical cancer. AB - Protein phosphatase 2A (PP2A) holoenzyme plays a critical role in cell cycle control and growth factor signaling. The PPP2R1B gene encodes the beta isoforms of the subunit A of the PP2A. We aimed to evaluate the role of the PPP2R1B gene in the pathogenesis of cervical cancer. Twenty-four women with primary cervical cancer were included. All resected specimens were divided into two groups: (1) cervical cancers (n = 24), (2) nearby noncancerous tissues (n = 24). We performed nested reverse transcriptase-polymerase chain reaction analysis and complementary DNA sequencing on the genomic DNA samples of all specimens. The aberrant transcripts and gene mutation as well as the genotype and allele frequencies of codon 66 CTA/CTG of PPP2R1B genes in both groups were compared. The percentages of aberrant transcripts between both groups were nonsignificantly different (20.8% vs 33.3%). There was no mutation in all specimens. The genotype and allele frequencies between both groups were non-different. Proportions of CTA homozygote/heterozygote/CTG homozygote were (1) 66.7/8.3/25% and (2) 58.3/12.5/29.2%. Proportions of CTA/CTG alleles in both groups were (1) 70.8/29.2% and (2) 64.6/35.4%. We conclude that PPP2R1B genes may not play a role in the carcinogenesis of cervical cancer. Mutations of PPP2R1B gene are not frequent in cervical cancer. PMID- 17343571 TI - The clinical values of squamous cell carcinoma antigen and carcinoembryonic antigen in patients with cervical cancer treated with concurrent chemoradiotherapy. AB - The objective of this study was to determine the prognostic significance of the pre- and posttreatment serum levels of the squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA). From 2001 to 2005, 211 patients were treated with concurrent chemoradiotherapy (CCRT). The SCC-Ag and CEA levels were measured before treatment, 1 month after treatment, and during the follow-up. The association between the pretreatment tumor marker levels and the clinical prognostic factors was evaluated. The frequency of complete remission (CR) and the normalization of the posttreatment tumor marker were also analyzed. The pretreatment serum levels of CEA and SCC-Ag were elevated in 68 (32.2%) and 148 (70.1%) patients, respectively. The number of patients with an elevated pretreatment SCC-Ag level was associated with the FIGO stage, tumor volume, and pelvic lymph node status. The pretreatment CEA was only significantly related to the tumor volume and pelvic lymph node involvement. One month after completing CCRT, the CEA and SCC-Ag levels were normalized in almost all patients with an incidence of 88.2% (60/68) and 93.2% (138/148), respectively. Among the patients who gained CR with a previously elevated pretreatment CEA and SCC-Ag, the values were normalized in 92.1% (58/63) and 96.4% (134/139) at 1 month, respectively. Combination assays of the pre- and posttreatment serum CEA and SCC-Ag levels appear to be useful for both predicting the prognosis and estimating the clinical response in cervical cancer. However, the routine combined measurement with SCC Ag of CEA in all patients had limited additional effect in predicting the prognostic significance. PMID- 17343572 TI - Loss of epithelium cadherin expression is associated with reduced overall survival and disease-free survival in early-stage squamous cell cervical carcinoma. AB - Epithelium cadherin (E-cad) is important for cell-to-cell adhesion of epithelial cells. Impairment of E-cad may have a role in the development and spreading of different malignancies and associated with poor differentiation, increased invasiveness, and poor prognostic factors in nongynecological carcinomas. However, prognostic significance of E-cad expression has not been investigated properly in cervical squamous cell carcinoma (SCC). The objective of this study was to investigate the association between reduced E-cad expression and clinicopathologic variables of cervical carcinoma. Specimens from 53 consecutive patients with stage IB-IIA SCC were evaluated immunohistochemically for E-cad expression, and the results were compared to grade, lymphvascular space invasion (LVSI), deep stromal involvement (DSI), parametrial involvement, lymph node metastasis, recurrences, and survival. Patients were divided into two groups arbitrarily: E-cad expression less than 10% (group 1) and E-cad expression more than 10% (group 2). There was no significant relationship between E-cad expression and DSI, LVSI, lymphatic metastasis. However, there was significant relationship between reduced E-cad expression and parametrial involvement (P= 0.024). Kaplan-Meier survival analysis revealed that reduced E-cad expression is significantly associated with reduced overall survival (OS) and disease-free survival (DFS). Furthermore, Cox regression analysis revealed that reduced E-cad expression is significantly associated with OS (P= 0.004, RR = 6.08, 95% CI: 1.75 21.1) and recurrences (P= 0.027, RR = 1.75, 95% CI: 1.06-2.88). We conclude that loss of E-cad expression is significantly associated with reduced OS and DFS in patients with SCC. Therefore, it might be used as an indicator of aggressive clinical behavior and tailoring aggressive adjuvant therapy in early-stage SCC. Further studies with larger number of patients are needed to evaluate the clinical significance of reduced E-cad expression in SCC. PMID- 17343573 TI - Ovarian tumors of borderline malignancy: a review of 247 patients from 1991 to 2004. AB - Borderline ovarian tumors account for 15% of epithelial ovarian cancers and are different from invasive malignant carcinoma. Majority are early stage, occurring in women in the reproductive age group, where fertility is important. We reviewed retrospectively 247 such cases treated at the Gynaecological-Oncology Unit, KK Women's and Children's Hospital, between January 1991 and December 2004. The mean age was 38 years (16-89 years). Majority of the cases (92%) were FIGO stage I (Ia, 75%; Ib, 1%; and Ic, 16%). Seven (3.5%) patients were diagnosed as having stage II disease, six (2.5%) as stage IIIa, two (1%) as stage IIIb, and four (2%) as stage IIIc. Histological origin was as follows: mucinous (68%), serous (26%), endometrioid (2.6%), and clear cell (1.2%). Primary surgical procedures undertaken were as follows: hysterectomy with bilateral salpingo-oophorectomy (52%), unilateral salpingo-oophorectomy (33%), or ovarian cystectomy (15%). Adjuvant chemotherapy was administered in 13 patients (5.2% of cases), of which 4 patients were given chemotherapy only because of synchronous malignancies. There were six recurrences (2.4% of cases). Overall mean time to recurrence was 59 months. Recurrence rate for patients who underwent a primary pelvic clearance was 1.6% compared to fertility-sparing conservative surgery (3.3%; although P= 0.683). No significant difference was noted in recurrence and mortality between staged versus unstaged procedures. The overall survival rate was 98.0%. There were a total of five deaths (2.8%): three (1.5%) from invasive ovarian/peritoneal carcinoma and two from synchronous uterine malignancies. It appears that surgical resection is the mainstay of treatment, with conservative surgery where fertility is desired or pelvic clearance if the family is complete. Surgical staging is important to identify invasive extraovarian implants that portend an adverse prognosis. The role of adjuvant chemotherapy is not established. PMID- 17343574 TI - Validity of positron emission tomography using fluoro-2-deoxyglucose for the preoperative evaluation of endometrial cancer. AB - To clarify the validity of positron emission tomography using fluoro-2 deoxyglucose (FDG-PET) for the preoperative evaluation of endometrial cancer, we analyzed the preoperative FDG-PET images of both primary and metastatic lesions of 30 patients with endometrial cancer, and compared them with computed tomography (CT) and/or magnetic resonance imaging (MRI) images and the results of postoperative pathologic findings. As to the primary lesions, FDG-PET could easily identify the cancer, and the sensitivity was 96.7%, which tended to be higher than that of 83.3% by CT/MRI. As to the evaluation of retroperitoneal lymph node metastasis, FDG-PET could detect none of five cases of lymph node metastatic lesions of up to 0.6 cm in diameter but had higher specificity (100%) compared with CT/MRI (85.7%). The sensitivity of FDG-PET for detection of extrauterine lesions excluding retroperitoneal lymph nodes was 83.3% and was superior to that of CT/MRI (66.7%), although there was no difference in the specificity between the modalities (100%). The diagnostic ability of FDG-PET was limited if used alone, but FDG-PET gave additional information especially with regard to the extrauterine lesions whose significance could not be determined on CT/MRI. However, we also found that FDG-PET could not identify any lymph node metastasis less than 1 cm in diameter; therefore, a negative finding of lymph node metastasis on FDG-PET should not be interpreted as a reason for omitting retroperitoneal lymph node dissection for the precise surgical staging of endometrial cancer. PMID- 17343575 TI - Decreased prevalence of dysplasia in high-risk population immigrants in a low risk area for cervical cancer. AB - Incidence rates of cervical cancer and its precursors vary considerably, with the highest rates found in developing countries. Differences are influenced by endogenous and exogenous factors. Comparing cytologic abnormality incidence rates from a high-risk population in the original high-risk area, with those of women from this high-risk population who have immigrated to a low-risk area could give insight in the significance of endogenous versus environmental factors. Smears collected from Surinamese women attending the Surinamese screening program and smears collected from immigrant Surinamese women attending the Dutch screening program were cytologically analyzed using the Dutch microscopical coding system KOPAC. Statistical analysis was performed by using logistic regression to calculate (age-adjusted) odds ratios (ORs). The age-adjusted ORs of having dysplasia were higher for Surinamese women living in Suriname versus Surinamese immigrant women and increased with increasing P-scores: 0.77 (0.31-1.91) for borderline changes, 1.62 (0.58-4.57) for mild dysplasia, and 3.20 (1.55-6.60) for moderate to severe dysplasia/neoplasia. We conclude that fewer cases with dysplasia are present in a high-risk population that has immigrated to a low-risk area for cervical cancer than in the high-risk population continuously living in a high-risk area. This finding emphasizes the importance of environmental factors. PMID- 17343576 TI - Calciphylaxis. PMID- 17343577 TI - Under-expression of VHL and over-expression of HDAC-1, HIF-1alpha, LL-37, and IAP 2 in affected skin biopsies of patients with psoriasis. AB - BACKGROUND: A feature of psoriasis is the rapid proliferation of keratinocytes, during which apoptosis is blocked and angiogenesis starts. It is known that tumor hypoxic cells produce histone deacetylase-1 (HDAC-1), which up-regulates hypoxia inducible factor-1alpha (HIF-1alpha) and down-regulates von Hippel-Lindau (VHL) protein by up-regulating vascular endothelial growth factor (VEGF) expression. It has been reported recently that the porcine peptide PR39 (homologous to human LL 37) has angiogenic and antiapoptotic activity. Thus, LL-37, induced by insulin like growth factor-1 (IGF-1), could help in the production of VEGF. PR39 also induces the expression of inhibitor of apoptosis protein-2 (IAP-2), which blocks apoptosis. The purpose of this work was to analyze whether these genes and their proteins are expressed in psoriatic biopsies. METHODS: Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) messenger RNA (mRNA) expression and immunohistochemical staining, we studied VHL, IAP-2, and related genes in skin biopsies from psoriatic patients and healthy subjects. RESULTS: An over-expression of the mRNA for HDAC-1, HIF-1alpha, LL-37, and IGF-1 in psoriatic skin, in comparison with skin from healthy subjects, was found. The antiangiogenic VHL mRNA and protein were under-expressed in psoriatic skin and highly expressed in healthy skin. The antiapoptotic IAP-2 was over-expressed in dermal endothelial cells from psoriatic skin. The pro-apoptotic Bax, Fas, and FasL mRNAs were expressed. CONCLUSIONS: These findings suggest that there could be an association of HDAC-1, HIF-1alpha, LL-37, VHL, and IAP-2 with angiogenic and apoptotic mechanisms in psoriasis. PMID- 17343578 TI - Arabic version of Skindex-16: translation and cultural adaptation, with assessment of reliability and validity. AB - BACKGROUND: Quality-of-life is increasingly recognized as an important measure in dermatology; however, most currently available dermatologic quality-of-life measures were originally created for the English language. Skindex-16 being one, is a self-administered questionnaire covering the symptoms, emotions and functioning aspects. OBJECTIVES: Our aim was to translate into Arabic and culturally adapt Skindex-16 following the international guidelines for cross cultural adaptation of health-related quality-of-life measures. Moreover, its validity and reliability would be assessed. METHODS: Translation and transcultural adaptation of Skindex-16 were performed. Subsequently, a cross sectional study was conducted where 678 persons (338 patients and 340 healthy people) responded to the Arabic version of Skindex-16. Evaluations of the semantic equivalence of back-translated items, reliability, construct validity, and content validity of the Arabic version were the main outcome measures. RESULTS: Two problematic items as well as the introductory (header) statement required a second translation and back-translation to achieve satisfactory agreement with the original instrument. The final Arabic version of Skindex-16 was internally reliable (Cronbach's alpha-range for the scales 0.81-0.92). The instrument demonstrated both construct and content validity. As hypothesized, the scores for dermatologic patients were higher than those for healthy persons (mean 31.5 vs. 21.1, P < 0.001, respectively). Similarly, scores for patients with inflammatory dermatosis were higher than those for patients with isolated skin lesions (mean 32.99 vs. 25.3, P < 0.05), indicating a poorer quality-of-life. However, greater than 63% of the patients' responses to an open-ended question about their skin disease were addressed by items in the instrument. CONCLUSION: We have developed a semantically equivalent translation with cultural adaptation of Skindex-16 into Arabic. The assessment of its measurement properties shows that it is quite reliable and a valid measure of the effects of skin diseases on the quality-of-life in Saudi patients. PMID- 17343579 TI - Epidemiology of pemphigus in Macedonia: a 15-year retrospective study (1990 2004). AB - BACKGROUND: Pemphigus is an autoimmune blistering skin disease mediated by auto antibodies directed against desmoglein proteins. There are only a few epidemiological studies on pemphigus. Our objective was to determine the epidemiological features of pemphigus in Macedonia, and to compare the results with those reported elsewhere. METHODS: Diagnosis in all cases was confirmed by histopathology and direct immunofluorescence. Binomial distribution testing and Fisher's exact-test at the 0.01 level of significance were used to determine if particular demographic groups were over-/ under-represented among the pemphigus patients. RESULTS: One hundred and thirty-three new pemphigus cases were diagnosed in Macedonia from 1990-2004. The average annual incidence was 0.44/100,000 inhabitants (SD = 0.17). The incidence doubled to 0.89 in 2001 during the local armed unrest. The disease did not affect either gender to a greater extent. The average annual incidence was 0.51 for ethnic Macedonians. Roma (Gypsies) had a statistically significantly higher incidence of pemphigus at 2.4 cases/100,000 individuals. Ethnic Albanians had statistically significantly lower incidence of 0.1 cases/100,000 individuals. The most common variant was pemphigus vulgaris (77.4%). CONCLUSIONS: The annual incidence for pemphigus in Macedonia is 0.44 cases/100,000 inhabitants. Most common form was pemphigus vulgaris. An epidemiological peak occurred in 2001 during the local armed conflict. Macedonian Roma had a sixfold higher incidence of pemphigus compared with the overall population; ethnic Albanians had a fourfold lower incidence. PMID- 17343580 TI - Antisense oligonucleotide targeting fibroblast growth factor receptor (FGFR)-1 stimulates cellular activity of hair follicles in an in vitro organ culture system. AB - BACKGROUND: The hair cycle is regulated by various molecules, among which FGF-5 has been shown to promote the transition from anagen to catagen. The FGFR-1, a trans-membrane receptor of FGF-5 with tyrosine kinase activity, is localized in the follicular papilla of hair follicles. OBJECTIVES: In order to apply the antisense oligonucleotides targeting FGFR-1 as a treatment for baldness, we examined the effect of the oligonucleotides on hair follicle growth in a serum free organ culture system. METHODS: Vibrissal hair follicles from C3H/He mice were cultured in the presence of a reagent at 31 degrees C in 95% O(2)-5% CO(2) for 72 h. A 20-mer antisense nucleotide and its randomly arranged counterpart were prepared by predicting the effective target site of FGFR-1 mRNA. Cellular activity in the hair bulb was estimated by measuring the fluorescence intensity (FI) of the medium after incubation with AlamarBlue dye. RESULTS: The addition of 30 microM of the phosphorothioate form of antisense oligonucleotide (A1561TS) to the media increased the FI by 30%, whereas the control produced no detectable change. This effect was reproducible dose-dependent with maximal stimulation at 30 microM. Incorporation of the oligonucleotide into the follicular papilla was histologically confirmed by incubation with FITC-labeled phosphorothioate oligonucleotides, and the intact morphological structure of the hair bulb was maintained intact after a 72-h incubation. CONCLUSIONS: These results suggest the clinical utility of antisense nucleotide targeting FGFR-1 as a treatment for baldness. PMID- 17343581 TI - Kaposi's sarcoma in Nigeria. AB - BACKGROUND: The prevalence of Kaposi's sarcoma (KS) in parts of Africa has been on the increase as a result of the human immunodeficiency virus (HIV) infection pandemic. However, there is a paucity of information for Nigeria. OBJECTIVE: To describe the clinical and epidemiological characteristics of cutaneous KS in patients with HIV-infection in Benin City, Nigeria. METHODS: All patients presenting to the dermatology and infectious diseases clinics of the University of Benin Teaching Hospital, or admitted to its medical wards, within the period July 2000-June 2005 were examined retrospectively in a chart review for KS. Diagnosis of HIV was based upon ELISA testing. The CD4(+) cell counts were performed using the Dyna Bead method and KS was diagnosed histologically. RESULTS: In our survey, 31 patients, representing 0.84% of all new HIV patients seen during the study period, had cutaneous KS. There were 19 males and 12 females, giving a male to female ratio of 1.6 : 1. The mean age was 36.3 +/- 9 years; mean CD4(+) count was 127 +/- 14 cells/dl. The lower limbs (74.2%), trunk (48.4%) and the face (22.6%) were the most frequent sites affected. The lesions were solitary in three patients (9.7%) and multiple in 28 patients (90.3%). CONCLUSION: The prevalence of HIV-related KS is increasing in Nigeria. There is an increase in the number of women being diagnosed with this form of KS, probably owing to more females having HIV disease. PMID- 17343582 TI - Molecular analysis of vitiligo lesions reveals sporadic melanocyte survival. AB - Vitiligo is a depigmenting disease of uncertain aetio-pathogenesis. Although accepted as dogma, the question of whether melanocytes survive in vitiligo lesions has not been adequately resolved. Defining with greater accuracy the melanocyte status of lesions would contribute greatly towards the understanding of the etiology, progression and treatment of this disorder. We have therefore revisited this issue by carrying out a molecular screen for melanocytes in lesional skin using the sensitive and specific technique of reverse transcription PCR (RT-PCR) followed by Southern blotting. Biopsies from vitiligo lesions and normal skin were obtained from 15 patients. The RT-PCR was carried out using primers for tyrosinase and dopa-chrome tautomerase (DCT). To increase the sensitivity of detection, Southern-blot analysis of all PCR products was conducted. Southern-blot analysis indicated that three lesional samples were positive: one for tyrosinase, one for DCT, and one for both. Lesions yielding positive results had been present for between 2-5 years and were inactive, as defined by no disease progression within the last 3 months. Some vitiligo lesions showed evidence of melanocyte survival, even after some years. These results open the way for the possibility of using a range of melanocyte-specific markers for molecular staging of lesional status by quantitative RT-PCR. Such information would be extremely valuable for the appropriate selection and potential success of medical therapies. PMID- 17343583 TI - Diagnostic approach and significance of inducible nitric oxide positivity in human cutaneous leishmaniasis caused by leishmania tropica. AB - AIM: To determine the usefulness of polymerase chain reaction (PCR) in the diagnosis of leishmaniasis and to emphasize the importance of inducible nitric oxide (iNOS). MATERIALS AND METHODS: Twenty-nine patients with cutaneous leishmaniasis diagnosed according to clinical criteria who live in rural areas of Antakya-Hatay/Turkey were included in this study. Twenty-five patients free of leishmaniasis were accepted as a control group. Punch biopsies and smears were obtained from lesions of the patients in the study group. Half of each punch biopsy specimen was processed in routine tissue processing. After routine tissue processing hematoxylin-eosin and iNOS immunohistochemical staining were applied. The remaining half of the biopsy specimens was studied by PCR method. INOS positive stained macrophages were determined. RESULTS: The positive detection rates in 29 cases of cutaneous leishmaniasis (CL) were 96.5% by PCR, 86.2% by direct microscopic evaluation of biopsy and 58.6% by direct visualization of smear in this study. iNOS reaction was mildly positive in three cases, moderately positive in six cases and strongly positive in 20 cases. CONCLUSION: iNOS yielded positive reaction in all cases but this positivity showed differences with respect to the age of the lesions or the effect of iNOS on the immune mechanism. This reveals an inverse correlation between iNOS reactivity and duration of lesion (Spearman correlation r = -0.53, P = 0.003). There was no correlation between iNOS reactivity and patient age (Spearman correlation: r = 0.13, P = 0.5). In terms of gender, there was no association with iNOS. PMID- 17343584 TI - Disseminated pheohyphomycosis. AB - A 40-year-old male agricultural laborer presented to our clinic with asymptomatic swellings on his left hand and left leg of 2 years' duration. A pea-sized swelling was first noticed on the back of the left hand, which was gradual in onset and slowly progressed to its present size. The patient later noticed multiple swellings over his left leg and thigh, with a similar progression. There was no history suggestive of inflammatory changes or discharge from the lesions. There was no previous history of trauma. The patient was an asthmatic and was on long-term oral steroid therapy (10-20 mg/day prednisolone). None of his family members had similar complaints. On physical examination, the patient was febrile. Cutaneous examination showed multiple, circumscribed, lobulated, non-tender, mobile, cystic swellings of various sizes, ranging from less than 2 cm over the left shin to more than 8 cm over the dorsum of the left hand and ankle (Fig. 1a,b). The surface over these swellings was shiny, smooth, and intact. The skin over the swellings was pliable and normal in color. There was no regional lymphadenopathy. The rest of the clinical examination was normal, except for decreased breath sounds over the left mid and lower pulmonary lobes. Routine laboratory tests, including complete blood count and liver and renal function tests, were within normal limits. Random blood glucose was greater than 400 mg%. Histopathologic examination of one of the cysts (from the hand) showed pheohyphomycotic cysts lined by dense fibrous tissue with chronic inflammatory infiltrate admixed with scattered giant cells in the dermis (Fig. 2). No fungal elements were visualized in the hematoxylin and eosin-stained sections. The fungal elements were found within the cystic cavity on special staining with Gomori's methenamine silver (GMS) and Masson-Fontana stains. The hyphae had irregularly placed branches and showed constrictions around their septae, thus resembling pseudohyphae and yeast forms (Fig. 3). Fine needle aspiration cytology from one of the swellings showed the presence of filamentous fungi on KOH examination and brown-pigmented distorted filaments and yeast-like cells on Masson-Fontana staining (Fig. 4a,b). The positive Masson-Fontana stain was indicative of the presence of melanin in the fungal hyphae, even when the fungal hyphae were not pigmented in the hematoxylin and eosin-stained section. Periodic acid-Schiff reagent also stained the fungal elements, thus confirming our diagnosis of pheohyphomycosis and ruling out the possibility of hyalohyphomycosis. The culture for fungus from the swelling aspirate grew contaminants. The chest X-ray showed dense nodular shadows in the left lower and mid pulmonary lobes. Sputum for acid-fast bacilli and Mantoux test were negative. During the hospital stay, the patient developed high fever and showed altered behavior, for which a computed tomography scan of the brain was performed; this showed evidence of multiple ring enhancing lesions in both frontal lobes. Ultrasound of the abdomen was normal. On the basis of the above findings, a diagnosis of disseminated subcutaneous pheohyphomycosis was made. The patient was given itraconazole, 100 mg twice daily, and his diabetes was managed with insulin. The fever stopped within a week and the altered behavior also started to show an improvement. There was obvious improvement in neurologic signs and symptoms. His skin lesions, however, responded slowly to the treatment. The patient did not report for further follow-up after 1 month. PMID- 17343585 TI - Trichosporon inkin subcutaneous infection in a rheumatoid arthritis patient. AB - A 74-year-old woman presented with painful ulcerative nodules on the left forearm. She had received systemic steroid therapy for rheumatoid arthritis for several years. On physical examination, there were four hemorrhagic ulcerative nodules with a linear distribution on the left forearm (Fig. 1A). These nodules had developed over the course of 2 months, and the number of lesions had increased despite systemic antibiotic therapy. There was no sign of systemic dissemination of the disease. Biopsy of a nodule demonstrated suppurative granulomatous infiltration (Fig. 1B); the hyphae stained positive with periodic acid-Schiff (data is not shown) and Gomori-methenamine silver stains in the dermis (Fig. 1C). The biopsy specimen was cultured in Sabouraud's dextrose agar supplemented with cycloheximide with incubation at 26 degrees C. A yeast-like creamy colony grew in 1 week. The colony became yellowish gray in color and the surface folded radially after 4 weeks of incubation (Fig. 2A). Microscopic examination revealed arthroconidia and blastoconidia (Fig. 2B), and urease activity was positive. The fungus was identified as Trichosporon beigelii by yeast biochemical card (YBC, Biomerieux Vitek, Inc., Hazelwood, MO, USA). The sequences of rDNA obtained from the colony were amplified using polymerase chain reaction (PCR) primer, analyzing the sequences of the 5.8S and 28S rDNA regions for the genetic identification of the Trichosporon species. The sequences of the PCR product matched the corresponding sequences of the T. inkin strain with 99% accuracy (Fig. 2C). The patient was given oral itraconazole for 8 weeks with good clinical results. PMID- 17343586 TI - Bullous amyloidosis presenting as naproxen-induced photosensitivity. PMID- 17343587 TI - Facial peeling skin syndrome: a case report and a brief review. AB - Peeling skin syndrome is an extremely rare genodermatosis of possible autosomal recessive inheritance, characterized by asymptomatic spontaneous exfoliation of the stratum corneum at a subcorneal or intracorneal level. It usually presents at birth or appears later in early childhood. The condition may be generalized or localized. Here we describe a case of localized continual skin peeling limited to the facial skin in a 6-month-old infant, with two other members of the family affected with the same condition. A few cases of localized skin peeling limited to the acral surfaces have been described in the literature, but a familial case of localized skin peeling limited to the facial skin has not been described before. We believe that our patient represents a new subtype of peeling skin syndrome, limited to the skin of the face. PMID- 17343588 TI - Netherton syndrome: successful use of topical tacrolimus and pimecrolimus in four siblings. AB - Netherton's syndrome (NS) is a rare autosomal recessive disease comprised of ichthyosis in the form of ichthyosis linearis circumflexa, hair shaft defects and atopic manifestations with an elevated IgE level. Various therapeutic options have been used in NS with variable success. Tacrolimus and pimecrolimus belong to the family of calcineurin inhibitors. They bind cytoplasmic proteins and the resulting complex binds calcineurin, inhibiting its ability to dephosphorylate the nuclear factor of activated T cells, thus suppressing gene transcription. There have been conflicting reports of the usefulness of tacrolimus in NS patients, with systemic absorption being the main adverse outcome. Here we report four Saudi siblings (two boys and two girls) with NS who were treated with topical tacrolimus and pimecrolimus with good control of their skin disease without any toxic effect. To our knowledge, this is the second report of the use of topical pimecrolimus in NS in the English literature. PMID- 17343589 TI - Case of concurrent epidermolysis bullosa acquisita and anti-p200 pemphigoid--how to treat it? PMID- 17343590 TI - Cicatricial pemphigoid vegetans. AB - A 58-year-old woman with ulcerative colitis of 5 years' duration was first seen in March 2002 with a 5-month history of widespread erosions on the palate and gingiva, subtle scarring of the conjunctiva, and xerostomia accompanying a flare of ulcerative colitis. No skin lesions were observed. Direct immunofluorescence study performed on the oral mucosa showed a linear distribution of immunoglobulin G (IgG) and immunoglobulin A (IgA) at the dermal-epidermal junction. Indirect immunofluorescence demonstrated the presence of circulating IgG anti-basement membrane zone antibody. This patient was successfully treated with sulfasalazine 3 g/day. Two years later, however, she developed extensive, well-defined pustules and vegetating erosions on the skin, symmetrically localized in the inguinal and axillary folds and on the upper inner thighs (Fig. 1). At that time, mucous membrane involvement, except for subtle scarring conjunctivitis, was not observed. Laboratory findings were normal, except for colonoscopy, which disclosed cobblestoning and histologically well-circumscribed granulomas, confirming the diagnosis of ulcerative colitis. On the basis of the clinical features and the flare of coexistent ulcerative colitis, this patient was suspected of having pyoderma gangrenosum. Skin biopsy specimens showed acanthosis, papillomatosis, pseudo-carcinomatous hyperplasia, and subepidermal blisters overlying an infiltrate of leukocytes and eosinophils, which also extended into the lower epidermis (Fig. 2). Direct immunofluorescence of the perilesional skin demonstrated a linear distribution of IgG and IgA at the dermal epidermal junction. In vivo-bound IgG within the basement membrane zone was documented using laser scanning confocal microscopy, which disclosed the presence of immunoglobulins above collagen type IV and below laminin-5 (Fig. 3). Indirect immunofluorescence study showed the presence of circulating IgG anti-basement membrane zone antibody reacting with the roof and floor of salt-split skin. Characterization of the target antigen (courtesy of Professor Hashimoto of Kurume University, Kurume, Japan) was unsuccessful, as Western immunoblot study on both epidermal and dermal extracts was negative, as was immunoblot with purified laminin-5 and enzyme-linked immunosorbent assay with the NC16a epitope of BP180. Laser scanning confocal microscopy confirmed the diagnosis of cicatricial pemphigoid. Therapy consisting of prednisone 40 mg each morning and sulfasalazine 1.0 g three times daily led to rapid improvement of the skin lesions, but did not affect the conjunctival lesions. After 4 weeks, prednisone was tapered and sulfasalazine was continued at a reduced dose of 0.5 g three times daily. At that time, only post-inflammatory hyperpigmentation and atrophic scars were evident. PMID- 17343591 TI - Metastatic esophageal carcinoma masquerading as inflammatory breast carcinoma. AB - A 50-year-old Caucasian woman with a history of esophageal adenocarcinoma presented with a 3-week history of right breast swelling and progressive erythema. Twenty-two months prior to presentation, she had been diagnosed with adenocarcinoma of the esophagus (T3,N1,M1a) and underwent neoadjuvant chemoradiotherapy followed by surgical resection. On physical examination, the right breast was red, swollen (40% larger than the contralateral breast), tender to palpation, and warm to the touch (Fig. 1). No mass was palpable. On the basis of the clinical findings, inflammatory breast carcinoma was suspected. A punch biopsy revealed a poorly differentiated adenocarcinoma with extensive involvement of dermal lymphatics (Fig. 2). The clinical and histologic differential diagnosis included inflammatory breast carcinoma vs. metastatic esophageal adenocarcinoma to the skin of the breast. To resolve this question, immunohistochemical stains for estrogen and progesterone receptors and CDX-2 (BioGenex, San Ramon, CA, USA) were performed. CDX-2 is an intestinal homeobox gene expressed in gastrointestinal epithelium and gastrointestinal tumors. The tumor nuclei were positive for CDX-2 but negative for both steroid receptors (Fig. 3), confirming the diagnosis of metastatic esophageal adenocarcinoma. PMID- 17343592 TI - Cutaneous leiomyosarcoma, trichoblastoma, and syringocystadenoma papilliferum arising from nevus sebaceus. AB - A 54-year-old man presented with a recurrent swelling on the right occipital region of the scalp. Two months earlier, the patient had undergone an initial local excision of the lesion which had enlarged progressively over the previous 2 years on a hairless patch which had been present since birth. On examination, a 5 x 4-cm, pinkish, firm, ulcerated swelling was seen on the right occipital region with a scar running over it. The lesion was not fixed to the underlying bone and there was no regional lymphadenopathy. X-Ray of the skull was normal and no evidence of metastatic disease was identified. Wide local excision of the tumor was performed and it was sent for histopathologic examination. Specimens and slides of the earlier surgery performed elsewhere were also studied. The specimen of the initial surgery consisted of skin-covered tissue with an exophytic firm growth measuring 6 x 5 x 4 cm. The skin surface was rough with areas of ulceration. No necrosis was noted grossly. Microscopically, three distinct lesions were seen. One was a well-circumscribed tumor located in the superficial dermis with lobules of basaloid cell aggregates with peripheral palisading and with no epidermal connection. The lobules were surrounded by cellular fibrous tissue (Fig. 1). Unlike basal cell carcinoma, however, no cleft between the cellular aggregates and stroma was noted. Foci of pigmentation were seen within cellular lobules and these features were consistent with a diagnosis of tricho blastoma. The second tumor was seen adjacent to the first, and consisted of duct like structures and cystic spaces with papillary projections. These were lined by double-layered epithelium with stromal infiltration by plasma cells, which are features of syringocystadenoma papilliferum (Fig. 2). The third lesion was a spindle cell sarcoma which formed the major part of the lesion, diffusely infiltrating the dermis and subcutaneous tissue, elevating and ulcerating the overlying skin. The tumor consisted of interlacing fascicles of spindle cells with oval to elongated nuclei having finely dispersed chromatin and inconspicuous nucleoli. The tumor cells were seen encircling the sweat glands, without destroying them (Fig. 3). Nuclear pleomorphism was minimal, with a mitotic rate of 9-10 per high-power field. A small area of epidermal hyperplasia with acanthosis and papillomatosis overlying malformed highly placed sebaceous glands was the only evidence of a pre-existing nevus sebaceus. The status of the surgical margins was not clearly discernible. The wide excision specimen of the recurrent swelling consisted of a skin-covered nodule with ulceration, measuring 3 x 4 x 3 cm, with a gray-white whorled cut surface. No necrosis was noted grossly. Multiple sections showed only spindle cell sarcoma infiltrating the skin and subcutaneous tissue, morphologically similar to the earlier tumor, with ulceration of the overlying skin. The surgical margins were free from tumor. Immunohistochemical stains on the spindle cell sarcoma showed positive staining for smooth muscle actin (SMA) (Fig. 4), vimentin, epithelial membrane antigen (EMA), and S100. The tumor cells were negative for cytokeratin (CK), HMB45, desmin, glial fibrillary acidic protein (GFAP), CD34, and CD68. Correlating the histomorphology and immunohistochemical findings, a diagnosis of cutaneous leiomyosarcoma with tricho-blastoma and syringocystadenoma papilliferum arising on nevus sebaceus was made. The patient received postoperative radiotherapy and is disease free 8 months after diagnosis. PMID- 17343593 TI - Bacterial pyoderma in children and therapeutic options including management of community-acquired methicillin resistant Staphylococcus aureus. PMID- 17343594 TI - Pressure ulcers: a pilot study for treatment with collagen polyvinylpyrrolidone. AB - BACKGROUND: Chronic ulcers owing to pressure cause complications with respect to immobilization and develop through limited blood circulation. There are different treatments for these ulcers; nonetheless, the search for an efficient and economical option continues. One choice could be collagen-polyvinylpyrrolidone (clg-pvp). Presence of pressure ulcers in hospitalized patients constitutes a frequent medical problem which is difficult to manage and can be an entry route for infection. Also, restoring the dermic continuity offers a means of improving a patient's quality-of-life. OBJECTIVE: The aim of the study was to analyze whether cicatrization on pressure ulcers presents more rapidly with local cleaning with soap, application of zinc oxide paste and clg-pvp compared with local cleaning with soap, application of zinc oxide paste and placebo (saline solution with polyvinylpyrrolidone). METHODOLOGY: From July 2002 to April 2003 the authors conducted a clinical, comparative, prospective, longitudinal, randomized study. Coded flasks containing either clg-pvp or placebo were designated for patients according to a table of random numbers. The clg-pvp or placebo was applied to each patient's ulcers at a rate of 1.5 ml intradermically at the four equi-spaced points around the ulcer. The nominal diameter of each ulcer was measured at the start of the study and then weekly over a 3-week period. Statistical analysis was carried out using the SPSS (version 10; SPSS Inc., Chicago, IL) software program. RESULTS: The group treated with clg-pvp experienced a reduction in mean ulcer size from 3.4 to 1.41 cm in diameter, whereas in the placebo group the reduction was from 2.9 to 1.58 cm in diameter. Despite the greater diameter reduction in the first group, the lack of a statistically significant difference could have resulted from the short follow-up period and small sample size. PMID- 17343595 TI - Successful treatment of perianal Bowen's disease with imiquimod. AB - Although perianal Bowen's disease (BD) is a relatively uncommon malignancy, it is being detected with increasing frequency. It has a strong tendency for local recurrence and treatment remains controversial. The effectiveness of different treatment modalities, ranging from aggressive wide local excision with skin grafting to the application of a topical immune response modifier, remains uncertain. To our knowledge only two cases of perianal BD, successfully treated with imiquimod, have been reported. We wish to present the third case, effectively treated with imiquimod. PMID- 17343596 TI - Narrow-band UV-B phototherapy in childhood psoriasis. PMID- 17343597 TI - You're in the army now. World War II flame-thrower research at Fort Knox. PMID- 17343599 TI - Hidradenitis suppurativa is acne inversa. PMID- 17343600 TI - An example of photo-aggravated lichen sclerosus. PMID- 17343601 TI - Association of Behcet's disease with hematologic malignancies. PMID- 17343602 TI - Acne treated successfully with azithromycin? PMID- 17343605 TI - A phase II study of outpatient first-line paclitaxel, carboplatin, and bevacizumab for advanced-stage epithelial ovarian, peritoneal, and fallopian tube cancer. AB - The purpose of this study was to assess the response rate and toxicity of paclitaxel, carboplatin, and bevacizumab (PCB) primary induction therapy for the treatment of advanced-stage ovarian carcinoma. Twenty patients were treated with paclitaxel (175 mg/m(2)), carboplatin (AUC of 5 IV), and bevacizumab (15 mg/kg) of body weight; q21 days for six cycles. Bevacizumab was administered at cycles two through six. Patients received 116 cycles of PCB chemotherapy (median = 6, range 2-6) and were evaluable for toxicity assessment. Grade 3 and 4 neutropenia developed in 23.3% and 25% of cycles, with no incidence of grades 3/4 thrombocytopenia or anemia. Prior to cycle six, one patient was removed from the study due to grade 3 neuropathy and another patient was excluded due to clinical deterioration. There was no incidence of gastrointestinal perforations, and only two patients demonstrated grade 3 hypertension (HTN). No grade 4 HTN was observed. Eighteen patients were evaluated for response following induction therapy. Six demonstrated a complete response (30%) and ten exhibited a partial response (50%), resulting in a total response rate of 80%. One patient exhibited stable disease (5%), and one demonstrated disease progression (5%). The lack of bowel perforations and wound complications should mitigate some concerns regarding these side effects. This study suggests that first-line treatment with PCB can be safely administered to previously untreated advanced-stage ovarian carcinoma patients. The favorable toxicity results and reasonable response rate warrant additional study in a larger patient population. PMID- 17343606 TI - Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix. AB - Cervical cancer develops from the preneoplastic cervical intraepithelial neoplasia (CIN). Host factors are critical in regulating tumor growth and cytokines, which modulate immunologic control may be of particular importance. The objective of this study was to assess the production of cytokines by peripheral blood mononuclear cells (PBMCs) in Indian women with cancer cervix and CIN. Sixty patients with cancer cervix (including all FIGO stage I-IV), 35 patients with CIN, and 30 healthy controls were enrolled in this study. The human papillomavirus (HPV) 16 and 18 status was determined in all the study groups. The PBMC culture supernatant was collected for cytokine estimations by enzyme-linked immunosorbent assay (interleukin-2 [IL-2], interferon-gamma [IFN-gamma], interleukin-4 [IL-4], and interleukin-10 [IL-10]). IL-2 levels showed a significant decline in high-grade CIN and cancer patients, whereas IFN-gamma levels were decreased only in patients with advanced cancer cervix. An increase in the levels of IL-4 and IL-10 was found in all cancer cervix and CIN grade III patients, as compared to those with early CIN grades and healthy controls. The cytokine ratios decreased significantly (P < 0.001 for all the ratios), when cervical cancer patients were compared with controls and CIN cases. The type 2 and type 1 cytokine levels were significantly correlated (P < 0.000) with HPV status. We conclude that a pronounced shift from type 1 to type 2 cytokine production is associated with more severe disease. These data reinforce the need for detailed analysis of immune dysregulation in CIN and cancer cervix patients. PMID- 17343608 TI - Placental site trophoblastic tumor with an ovarian metastasis. AB - Placental site trophoblastic tumors (PSTT) are the rarest form of gestational trophoblastic disease (GTD). The clinical management of PSTT differs from the other forms of GTD as surgery plays a more important role. The most common metastatic sites are the lung, liver, and vagina while spread to the adnexa is relatively unusual. We describe a case of a 35-year-old woman presenting with PSTT and ovarian metastasis who was successfully treated with radical hysterectomy, bilateral oophorectomy, pelvic lymph node dissection, and postoperative chemotherapy. The case highlights the possibility of ovarian metastases despite normal preoperative imaging and confirms the value of multidisciplinary management of this rare illness. PMID- 17343607 TI - Phase II trial of imatinib mesylate in recurrent, biomarker positive, ovarian cancer (Southwest Oncology Group Protocol S0211). AB - Platinum-resistant ovarian cancer continues to be a difficult therapeutic problem. Clearly, molecularly targeted agents should be evaluated in this patient population. Patients were eligible for this phase II study with stage III or IV ovarian cancer, whose tumor expressed Kit (CD117) or platelet-derived growth factor receptor (PDGFR) and with relapse of measurable disease within 6 months of completing frontline, platinum- and taxane-based chemotherapy. Patients were treated daily with 400 mg of imatinib mesylate orally. It was assumed that the agent would be of no further interest if the population response rate was less than 10%. A two-stage design was used for patient accrual. A total of 34 patients were registered to the study. Of these, 15 were found to be ineligible or not evaluable (8 because their tumor samples were negative for both DC117 and PDGFR). Of 19 evaluable patients, 2 (11%) tested positively for c-Kit and 17 (89%) tested positively for PDGFR. There were no objective responders. Thirteen patients (68%) had increasing disease or symptomatic deterioration, and six (32%) went off protocol during the first month due to adverse events. Median progression-free survival was 2 months (95% CI 1-3 months) and median overall survival was 10 months (95% CI 6-18 months). Eleven percent of patients experienced grade 4 hematologic/metabolic toxicity and 37% experienced grade 3 nonhematologic toxicity. We conclude that imatinib mesylate as a single agent does not appear to have useful clinical activity in c-Kit and/or PDGFR positive, recurrent ovarian cancer in heavily pretreated patients with ovarian cancer. PMID- 17343610 TI - Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian cancer before age 40. AB - At least one of ten patients with ovarian cancer is estimated to develop their tumor because of heredity with the breast and ovarian cancer syndrome due to mutations in the BRCA1 and BRCA2 genes and hereditary nonpolyposis colorectal cancer (HNPCC) being the major genetic causes. Cancer at young age is a hallmark of heredity, and ovarian cancers associated with HNPCC have been demonstrated to develop at a particularly early age. We used the Swedish Cancer Registry to identify a population-based series of 98 invasive epithelial ovarian cancers that developed before 40 years. Mucinous and endometrioid cancers were overrepresented and were diagnosed in 27% and 16% of the tumors, respectively. Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of MSH2/MSH6 in one case, and loss of MSH6 only in three tumors. A microsatellite instability-high phenotype was verified in five of six tumors. Based on the identified mutations and family history of cancer, several of these individuals are likely to be affected by HNPCC. We conclude that although the causes of the vast majority of epithelial ovarian cancer at young age are unknown, HNPCC should be considered because of the high risk of metachronous colorectal cancer in the individual and the possibility of preventing additional cancers in the family through control programs. PMID- 17343611 TI - Response to the letter of Dr Thomas. PMID- 17343612 TI - Up-regulation of Fas (CD95) expression in tumour cells in vivo. AB - Both the function and regulation of Fas expression in tumours is poorly understood. Our laboratory has reported that cultured, low Fas-expressing tumours undergo massive, yet reversible, up-regulation of cell surface Fas expression when injected into mice. The present study was aimed at determining what causes this enhanced Fas expression and whether the newly expressed Fas functions as a death receptor. Newly expressed Fas is indeed capable of inducing apoptosis. Based on our observation that Fas induction is reduced when tumour cells are injected into immune-deficient mice, we propose that Fas up-regulation in vivo involves the host's immune system. Accordingly, Fas up-regulation occurs in vitro when low Fas-expressing tumour cells are cocultured with lymphoid cells. Furthermore ascitic fluid extracted from tumour-bearing mice trigger Fas up regulation in low Fas expressing tumours. This last finding suggests that a soluble factor(s) mediates induction of Fas expression. The best candidate for this soluble factor is nitric oxide (NO) based on the following observations: the factor in the ascites is unstable; Fas expression is induced to a lesser degree after injection into inducible NO synthase (NOS)-deficient (iNOS(-/-)) mice when compared to control mice; similarly, coculture with iNOS(-/-) splenocytes induces Fas less effectively than coculture with control splenocytes; and finally, the NO donor SNAP induces considerable Fas up-regulation in tumours in vitro. Our model is that host lymphoid cells in response to a tumour increase NO synthesis, which in turn causes enhanced Fas expression in the tumour. PMID- 17343613 TI - Development and characterization of novel photosensitizer : scFv conjugates for use in photodynamic therapy of cancer. AB - Photodynamic therapy (PDT) is becoming an evermore useful tool in oncology but is frequently limited by side-effects caused by a lack of targeting of the photosensitizer. This problem can often be circumvented by the conjugation of photosensitizers to tumour-specific monoclonal antibodies. An alternative is the use of single chain (sc) Fv fragments which, whilst retaining the same binding specificity, are more efficient at penetrating tumour masses because of their smaller size; and are more effectively cleared from the circulation because of the lack of an Fc domain. Here we describe the conjugation of two isothiocyanato porphyrins to colorectal tumour-specific scFv, derived from an antibody phage display library. The conjugation procedure was successfully optimized and the resulting immunoconjugates showed no loss of cell binding. In vitro assays against colorectal cell lines showed these conjugates had a selective photocytotoxic effect on cells. Annexin V and propidium iodide staining of treated cells confirmed cell death was mediated principally via an apoptotic pathway. This work suggests that scFv : porphyrin conjugates prepared using isothiocyanato porphyrins show promise for use as targeted PDT agents. PMID- 17343614 TI - Regulation of human T-cell homing receptor expression in cutaneous bacterial infection. AB - We investigated the regulation of T-cell homing receptors in infectious disease by evaluating the cutaneous lymphocyte antigen (CLA) in human leprosy. We found that CLA-positive cells were enriched in the infectious lesions associated with restricting the growth of the pathogen Mycobacterium leprae, as assessed by the clinical course of infection. Moreover, CLA expression on T cells isolated from the peripheral blood of antigen-responsive tuberculoid leprosy patients increased in the presence of M. leprae (2.4-fold median increase; range 0.8-6.1, n = 17), but not in unresponsive lepromatous leprosy patients (1.0-fold median increase; range 0.1-2.2, n = 10; P < 0.005). Mycobacterium leprae specifically up-regulated the skin homing receptor, CLA, but not alpha(4)/beta(7), the intestinal homing receptor, which decreased on T cells of patients with tuberculoid leprosy after antigen stimulation (2.2-fold median decrease; range 1.6-3.4, n = 3). Our data indicate that CLA expression is regulated during the course of leprosy infection and suggest that T-cell responsiveness to a microbial antigen directs antigen specific T cells to the site of infection. PMID- 17343615 TI - Impact of class A, B and C CpG-oligodeoxynucleotides on in vitro activation of innate immune cells in human immunodeficiency virus-1 infected individuals. AB - Oligodeoxynucleotides (ODN) with unmethylated deoxycytidyl-deoxyguanosine dinucleotides (CpG-ODNs) stimulate Toll-like receptor 9 (TLR9) in plasmacytoid dendritic cells (pDC) and B cells and activate innate and adaptive immunity. Three classes of synthetic CpG-ODNs, class A, B and C, activate cells through TLR9; our goal was to evaluate their effect on cells from human immunodeficiency virus (HIV)-1(+) individuals. We compared the frequencies and the unstimulated activation status of immune effector cells in HIV-1(+) and HIV-1(-) individuals. Fewer pDC, myeloid dendritic cells (mDC), B cells, natural killer (NK) cells and invariant natural killer T cells (iNKT) were present in HIV-1(+) peripheral blood mononuclear cells (PBMC) and their baseline activation status was higher than HIV 1(-) PBMC. Exposure of HIV-1(+) PBMC to all classes of CpG-ODNs led to activation and maturation of pDC based on CD86, CD80, and CD83 expression similar to that of cells from HIV-1(-) individuals. The percentage of CpG-ODN stimulated pDC that express CD40 was dramatically higher when cells were obtained from HIV-1(+) than from HIV-1(-) individuals. B-lymphocytes were activated similarly in HIV-1(+) and HIV-1(-) individuals. mDC, NK and iNKT cell, which lack TLR9, were indirectly activated. Interferon-alpha (IFN-alpha) and interferon inducible protein 10 (IP 10) secretion was induced by class A or C but not class B CpG-ODN, but the concentrations were less than those produced by HIV-1(-) PBMC. HIV-1 infected individuals have fewer innate effector cells that are chronically activated, but these cells can be further activated by CpG-ODN, which suggests that synthetic CpG-ODNs could be used to enhance the immune system in HIV-1 infected individuals. PMID- 17343616 TI - Interleukin-4 inhibition of osteoclast differentiation is stronger than that of interleukin-13 and they are equivalent for induction of osteoprotegerin production from osteoblasts. AB - Interleukin (IL)-4 and IL-13 are closely related cytokines known to inhibit osteoclast formation by targeting osteoblasts to produce an inhibitor, osteoprotegerin (OPG), as well as by directly targeting osteoclast precursors. However, whether their inhibitory actions are the same remains unclear. The inhibitory effect of IL-4 was stronger than that of IL-13 in an osteoclast differentiation culture system containing mouse osteoblasts and osteoclast precursors. Both cytokines induced OPG production by osteoblasts in similar time- and dose-dependent manners. However, IL-4 was stronger in direct inhibition that targeted osteoclast precursors. Furthermore, IL-4 induced phosphorylation of signal transducer and activator of transcription-6 (STAT6) at lower concentrations than those of IL-13 in osteoclast precursors. IL-4 but not IL-13 strongly inhibited the expression of nuclear factor of activated T-cells, cytoplasmic 1 (nuclear factor-ATc1), a key factor of osteoclast differentiation, by those precursors. Thus, the activities of IL-4 and IL-13 toward osteoclast precursors were shown to be different in regards to inhibition of osteoclast differentiation, whereas those toward osteoblasts for inducing OPG expression were equivalent. PMID- 17343617 TI - Contact allergy epidemics and their controls. AB - Contact dermatitis can be severe and lead to sick leave as well as significant healthcare expenses. The aim of this review is to present the published knowledge on 6 historical epidemics of contact allergy to apply this knowledge on the prevention and control of future contact allergy epidemics. A historical review is performed on nickel, chromium, methyl-chloro-iso-thiazolinone/methyl-iso thiazolinone, methyl-di-bromo glucaro-nitrile, formaldehyde, and para phenylenediamine. The first cases of contact dermatitis are mostly occupational, whereas consumer cases appear later. There is often a latency period from the first cases are observed until an epidemic occurs, and the problem is recognized. Finally, no one seems to take responsibility of dealing with the situation, and there are no attempts of regulation until an epidemic is consolidated among consumers for many years. Steps should be taken to prevent contact allergy epidemics. It is essential that dermatologist, scientists, administrators, and consumers organize and structure known methods to accelerate the control of emerging contact allergens. PMID- 17343618 TI - The skin sensitization potential of resorcinol: experience with the local lymph node assay. AB - Resorcinol is a simple aromatic chemical (1,3-benzenediol) that has found widespread use, particularly as a coupler in hair dyes. Clinical experience clearly shows that resorcinol is a (albeit uncommon) skin sensitizer. By contrast, predictive methods, both animal and human, have previously failed to identify resorcinol as such. Here, we describe the outcome of a recent local lymph node assay performed in accordance with Organisation for Economic Co operation and Development guideline 429, which correctly identified resorcinol as a skin sensitizer. Clear evidence of a dose response was apparent, and an EC3 value of approximately 6% was calculated. This suggests that the skin-sensitizing potency of resorcinol is approximately 2 orders of magnitude lower than that of p phenylenediamine but similar to that of hexyl cinnamic aldehyde. These data show the importance of adherence to test guidelines and aligns the clinical experience with resorcinol with that obtained in predictive animal methods. PMID- 17343619 TI - Selected important fragrance sensitizers in perfumes--current exposures. AB - Contact allergy to fragrance ingredients is frequent. Recommendations and regulations of some of the most frequent and potent fragrance allergens have recently been introduced. To investigate current exposures to 4 important fragrance allergens in hydroalcoholic cosmetic products. 25 popular perfume products of Danish as well as international brands were purchased from the Danish retail market. Contents of 4 important fragrance allergens, isoeugenol, hydroxy iso-hexyl 3-cyclohexene carboxaldehyde (HICC, Lyral), were determined by gas chromatography-mass spectrometry, and atranol and chloro-atranol were determined by liquid chromatography-tandem mass spectrometry. Isoeugenol was found in 56%, HICC in 72%, atranol in 59%, and chloro-atranol in 36% of the 22 eau de toilette/eau de parfum products. The concentrations of isoeugenol were, in all products, below the recommended maximum concentration of 0.02%. HICC reached a maximum of 0.2%, which is 10-fold higher than maximum tolerable concentration considered safe by the EU Scientific Committee. The median concentrations of atranol and chloro-atranol in the investigated products were similar to those found in similar products in 2003. A significant decrease in the frequency of presence of chloro-atranol in the products was observed. There is still a wide spread exposure to potent fragrance allergens in perfumes. PMID- 17343620 TI - Time trends in Swedish patch test data from 1992 to 2000. A multi-centre study based on age- and sex-adjusted results of the Swedish standard series. AB - Allergic contact dermatitis is recognized as a public health problem and some major allergens have been subject to intervention aiming at lowering skin exposure. There is an obvious interest in evaluating the effect of such interventions. Population studies are difficult to perform and epidemiological studies based on clinical data from testing patients with contact dermatitis are common surrogates. Our objective was to gather Swedish clinical standard series test data on two occasions in order to monitor trends in sensitization rates. Consecutive patch test results from the Swedish standard series were collected from 9 centres from 1991 to 1993 and from 1999 to 2001. In total, 3680 and 3790 patients, respectively, were included. Crude, age-adjusted and age-stratified prevalence are given separately for women and men. Our top 10 allergens are much in line with newly published European test data. Significant changes among those allergens are increasing sensitization rates for Myroxylon pereirae and decreasing rates for colophony, 5-chloro-2-methyl-4-iso-thi-azo-lin-3-one, Amerchol L 101 and thiuram mix. Nickel allergy is decreasing among young women. Among less common allergens, a noteworthy increase of sensitization to 4-phenyl en-diamine is found. In conclusion, significant trends in sensitization rates of important allergen, reflecting changes in exposure, have been found. PMID- 17343621 TI - Frequency of dermatoses associated with cosmetics. AB - The objectives of this study were (i) to determine the frequency of dermatoses caused by use of cosmetics in patients with specific complaints of reaction to cosmetic products, and (ii) to observe the main skin conditions frequently misunderstood by users as cosmetic reactions. 176 patients seen in a private office from 1999 to 2006, with complaint of dermatoses caused by cosmetics were examined. The clinical history, physical examination, relation between site of reaction and use of cosmetics were assessed. Of the patients examined, 154 (87.5%) were women and 22 (12.5%) men. About 90 (52%) patients had no skin condition related to cosmetics, 80 (45%) had dermatoses associated with cosmetics, and 6 patients (3%) had inconclusive results. Melasma, contact dermatitis to other products, and acne were the conditions that users associated more often to cosmetics. 14% of patients had skin lesions caused by inappropriate cosmetic use. To conclude, the true adverse reaction to cosmetics was not very common. In this study, dermatitis was associated with cosmetics in only 31% of patients with specific complaint of dermatitis caused by cosmetics. Therefore, 52% of patients misdiagnosed the condition and had other dermatoses, and 14% made inappropriate use of cosmetics. PMID- 17343622 TI - Long-lasting patch reactions to gold sodium thiosulfate occurs frequently in healthy volunteers. AB - In a skin irritancy study in healthy volunteers with 3 metal salts, aqueous gold sodium thiosulfate (GSTS) in a dilution series caused unexpectedly frequent and strong patch test reactions on volar forearm skin in 22 of 31 participants (71%). The reactions showed morphological features consistent with a contact allergic reaction, and the crescendo type of the response speaks in favour of an allergic nature. Further, 8 of the 31 (26%) developed long-lasting test reactions. A follow-up interview among 28/31 participants 10 years later showed that none had experienced long-term consequences in the form of skin and/or mucosal complaints related to exposure to gold items. The results indicate that inclusion of GSTS in routine patch testing may cause problems regarding interpretation and clinical relevance of positive GSTS patch tests, which fulfil the clinical criteria of a contact allergy. PMID- 17343623 TI - Identification of subjects with atopic dermatitis in questionnaire studies. AB - The performances of 3 different atopic dermatitis questions from the Danish translation of the Nordic Occupational Skin Questionnaire (NOSQ-2002) were compared with respect to their ability to identify subjects with atopic dermatitis in workplace studies. The wording of the questions were: 'Have you ever had an itchy rash that has been coming and going for at least 6 months, and at sometime has affected skin creases?' (UK question), 'Have you ever had eczema on the fronts of the elbows or behind the knees?' (Nordic-S5a) and 'Have you ever had childhood eczema?' (Nordic-S5b). In a group with occupational exposure including the forearms (gut cleaners) twice as many (44%) answered 'Yes' to the UK question compared with 2 other studies on dairy workers and hospital employees. The question Nordic-S5b gave rise to less positive answers than expected. The Nordic-S5a question gave rise to 15%, 10% and 15% positive answers, respectively, and these frequencies seemed to be independent of the workplace exposure. In conclusion, we recommend the Nordic-S5a question as the question to be used for identification of subjects with atopic dermatitis in adult workplace populations. Furthermore, we found that the UK question led to over-reporting in an adult workplace population with occupational exposure including the forearms. PMID- 17343624 TI - Airborne contact dermatitis due to Japanese cedar pollen. AB - Contact dermatitis caused by airborne antigen is a well-recognized problem. Previously, airborne contact dermatitis after contact with Japanese cedar pollen [Japanese cedar pollen dermatitis (JCPD)] has been reported in Japan. However, there is still no diagnostic test to evaluate contact dermatitis due to Japanese cedar pollen. Skin tests with Japanese cedar pollen have been used to investigate these patients. A histological analysis was also conducted to clarify the mechanism of JCPD. We performed a scratch-patch test, scratch test and assays for total immunoglobulin E (IgE) and specific IgE in 13 patients suspected to have skin symptoms from Japanese cedar pollen, 5 patients with Japanese cedar pollinosis and 15 control normal subjects. All subjects were tested with Japanese cedar pollen allergen extract. A skin biopsy was performed from a Japanese cedar pollen-scratch-patch-test positive in patients with JCPD. The result after 48 hr of scratch-patch test was compared with the patient's history and the findings of corresponding scratch test and specific IgE. 100% of the 13 patients with JCPD showed a positive scratch-patch-test reaction to Japanese cedar pollen extract. However, 20% of the patients with the Japanese cedar pollinosis without any eruptions showed a positive scratch-patch-test reaction. The percentage of positive results for specific IgE and the scratch test did not differ substantially between Japanese cedar pollionosis patients with a history of chronic erythema after contact with Japanese cedar pollen and those without such a history. No side-effects were observed regarding the scratch-patch test. Control subjects showed 7% positive reaction. Histological examination showed that eczematous change (spongiosis, intracellular oedema and acanthosis), and infiltration of lymphocytes and eosinophils were all observed at the scratch patch-test-positive sites. We therefore concluded that the use of the scratch patch test with Japanese cedar pollen extract was useful for accurately diagnosing JCPD. PMID- 17343625 TI - Contact allergy to topical medicaments becomes more common with advancing age: an age-stratified study. AB - Eczema is common in the elderly people who often use topical medicaments. Previous studies in the elderly people have noted allergic positive patch tests in between 43% and 64% of those tested. We set out to assess whether medicament contact allergies are more common in elderly patients. We undertook a retrospective age-stratified study of all patients patch tested at the Royal Hallamshire Hospital, Sheffield, between January 1994 and July 2005. We confirmed that contact allergy to topical medicaments is more common in those aged more than 70 years compared with the younger age groups. There was no sex difference. The commonest problematic allergen types found in medicaments were fragrances and preservatives. The most frequent individual allergens were fragrance mix, Myroxylon pereirae, lanolins, local anaesthetic agents, neomycin and gentamicin, and tixocortol pivolate. The pattern of medicament contact allergens was similar to that of the younger age groups except that multiple allergic positives were more frequent and sensitivities to local anaesthetics and Myroxylon pereirae were proportionally more common. Elderly patients were more likely to have multiple contact allergies than the younger ones. Care needs to be taken when prescribing topical medicaments to elderly patients with eczema, especially for preparations that contain perfumes, lanolins, and local anaesthetics. PMID- 17343626 TI - Contact allergy in male construction workers in Sao Paulo, Brazil, 2000-2005. AB - There are no recent data on allergens in the construction industry in Brazil; apparently there were no changes in allergenic substances. The objective of this study was to identify sensitization to allergens in adult males working in the construction industry. A cross-sectional study with adult males submitted to patch tests from May 2000 to December 2005. Out of 169 male patients, 83 were construction workers. The five most frequent allergens among the construction workers were potassium dichromate (57%), carba-mix (34.9%), cobalt chloride (30.2%), thiuram-mix (27.9%) and neomycin (19.8%). There is a significant sensitization to potassium dichromate, cobalt, carba-mix, and thiuram-mix, demonstrating that cement and rubber gloves of personal protection equipment still account for allergic contact dermatitis in construction industry workers. PMID- 17343627 TI - The biocide polyhexamethylene biguanide remains an uncommon contact allergen. AB - Polyhexamethylene biguanide (PHMB) is used as a preservative in cosmetics and personal care products. Previous studies had shown a frequency of sensitization to PHMB of 0.5% and 0.4% in unselected dermatitis patients. The objective of this study was to determine the current frequency of sensitization to PHMB. From July 2005 until December 2005, a total of 1975 consecutive patients were patch tested with PHMB. 10 patients (0.5%) had positive patch test reactions to PHMB 2.5% aq. (9+ and 1++) and 16 patients (0.8%) to PHMB 5.0% aq. (12 +, and 4 ++). The test reaction pattern (reaction index and positivity ratio) of both preparations and a limited concordance between results from both concentrations (Cohen's kappa = 0.35) are probably indicative of a substantial number of false positive reactions. Potential causal exposures were assessed by a case by case analysis and by referring to surrogate markers of exposure in terms of concomitant reactions. Occupational exposures were identified as a probable cause of sensitization. Further risk factors included leg dermatitis and old age. The frequency of sensitization remains low. It is very unlikely that exposure to cosmetics or personal care products may have played a role in the few cases sensitized. PMID- 17343628 TI - Amalgam-tattoo-associated oral lichenoid lesion. AB - We report on a lichenoid reaction that developed in association with amalgam particles within an amalgam tattoo of the oral mucosa. PMID- 17343629 TI - Immediate hypersensitivity to paraphenylenediamine. PMID- 17343630 TI - Sodium metabisulfite--a marker for cosmetic allergy? AB - A 45-year-old woman developed dermatitis of the face after she applied a cosmetic package comprising day and night creams. Patch tests were performed with the British Contact Dermatitis Society (BCDS) standard, bases + preservatives, and cosmetic series in addition to samples of both creams and the individual constituents. She had positive tests to both cosmetic creams, sodium sulfite from the manufacturer's samples (5% white soft paraffin (WSP)), and sodium metabisulfite (1% pet) in our bases + preservatives battery. Sodium sulfite is a constituent of both cosmetic creams. We assume that the positive test to sodium metabisulfite is a cross-reaction. We hypothesize that a reaction to sodium metabisulfite may be a marker for sulfite allergy in cosmetics and might account for some of the unexplained positives in previous reports. PMID- 17343631 TI - Allergic contact cheilitis due to geraniol in food. AB - Fragrance materials are present in many foods and are referred to as flavours and spices. However, despite their widespread use, there are few reports of allergic contact dermatitis caused by these additives. Here, we report contact allergy to geraniol in a patient who developed cheilitis on exposure to certain foods. PMID- 17343632 TI - Clarinetist's cheilitis caused by immediate-type allergy to cane reed. PMID- 17343633 TI - Allergic contact dermatitis to purpleheart and padauk wood (Pterocarpus dalbergiodes). PMID- 17343635 TI - Designing out vulnerability, building in respect: violence, safety and sex work policy. AB - One recent finding about the prostitution market is the differences in the extent and nature of violence experienced between women who work on the street and those who work from indoor sex work venues. This paper brings together extensive qualitative fieldwork from two cities in the UK to unpack the intricacies in relation to violence and safety for indoor workers. Firstly, we document the types of violence women experience in indoor venues noting how the vulnerabilities surrounding work-based hazards are dependent on the environment in which sex is sold. Secondly, we highlight the protection strategies that indoor workers and management develop to maintain safety and order in the establishment. Thirdly, we use these empirical findings to suggest that violence should be a high priority on the policy agenda. Here we contend that the organizational and cultural conditions that seem to offer some protection from violence in indoor settings could be useful for informing the management of street sex work. Finally, drawing on the crime prevention literature, we argue that it is possible to go a considerable way to designing out vulnerability in sex work, but not only through physical and organizational change but building in respect for sex workers rights by developing policies that promote the employment/human rights and citizenship for sex workers. This argument is made in light of the Coordinated Prostitution Strategy. PMID- 17343636 TI - Connecting the gendered door: women, violence and doorwork. AB - This paper explores the emerging role of women who work as 'bouncers', or doorstaff, in the night-time economy and examines how the cultural capital of the female bouncer is connected to the methods utilized to control licensed premises. It is drawn from a study that combined ethnographic observations and interviews in five major UK cities which explored a diverse range of issues such as gendered bodies, femininities and violence; the changing needs of the night-time economy in the UK and the experiences of women engaged in 'non-traditional' occupations. In this paper, we draw on interview data with one particular category of female door staff; women who share similar histories of exposure to violence and violent cultures, and we examine how their experiential knowledge of violence equips them with the resources to 'work the doors'. Our attention focuses on this group of women, who we refer to as 'The Connected', and examine how they are 'doing gender' when they negotiate violence 'on the door' PMID- 17343637 TI - The changing practice of eating: evidence from UK time diaries, 1975 and 2000. AB - This paper examines some central themes about change in consumption behaviour through an empirical investigation of the practice of eating. It analyses patterns of food consumption in the UK using time diary data from 1975 and 2000. The practice of eating is decomposed into four component activities which are used to explore systematically the inter-relationships between social processes - such as commodification and temporal fragmentation - and ways of providing and consuming food. It charts the expansion of eating out, the degree to which it substitutes for other eating activities, and the implications of its development for social relations and the temporal organization of daily life. Analysis reveals that food consumption continues to be differentiated along established lines of social division, although the content of those divisions has changed and varies across components of the practice. Increasing commodification of the food chain is documented, but without appearing to have a corrosive impact on household organization or social relationships. While tendencies indicative of temporal fragmentation are revealed, counter-tendencies exist which suggest that the practice of eating is resilient to many forms of external pressure. Finally, the application of a practice-based analytical approach permits critical evaluation of theories of social transformation. PMID- 17343638 TI - Ordering competition: the interactional accomplishment of the sale of art and antiques at auction. AB - Auctions provide an institutional solution to a social problem; they enable the legitimate pricing and exchange of goods where those goods are of uncertain value. In turn, auctions raise a number of social and organizational issues that are resolved within the interaction that arise in sales by auction. In this paper, we examine sales of fine art, antiques and objets d'art and explore the ways in which auctioneers mediate competition between buyers and establish a value for goods. In particular, we explore how bids are elicited, co-ordinated and revealed so as to rapidly escalate the price of goods in a transparent manner that enables the legitimate valuation and exchange of goods. In directing attention towards the significance of the social interaction, including talk, visual and material conduct, the paper contributes to the growing corpus of ethnographic studies of markets. It suggests that to understand the operation of markets and their outcomes, and to unpack issues of agency, trust and practice, we need to place the 'interaction order' at the heart of analytic agenda. PMID- 17343639 TI - Operationalizing Max Weber's probability concept of class situation: the concept of social class. AB - In this essay I take seriously Max Weber's astonishingly neglected claim that class situation may be defined, not in categorial terms, but probabilistically. I then apply this idea to another equally neglected claim made by Weber that the boundaries of social classes may be determined by the degree of social mobility within such classes. Taking these two ideas together I develop the idea of a non categorial boundary 'surface' between classes and of a social class 'corridor' made up of all those people who are still to be found within the boundaries of the social class into which they were born. I call social mobility within a social class 'intra-class social mobility' and social mobility between classes 'inter-class social mobility'. I also claim that this distinction resolves the dispute between those sociologists who claim that late industrial societies are still highly class bound and those who think that this is no longer the case. Both schools are right I think, but one is referring to a high degree of intra class social mobility and the other to an equally high degree of inter-class mobility. Finally I claim that this essay provides sociology with only one example among many other possible applications of how probability theory might usefully be used to overcome boundary problems generally in sociology. PMID- 17343640 TI - Putting Adam Ferguson in his place. AB - This paper re-conceptualizes the relationship between Ferguson's life and work by locating him in his biographical and geographical context for the purposes of better understanding his proto-sociological writings. Ferguson's work is relatively unknown outside limited sets of literature and current representations of the link between his life and work risk misplacing him as both Scotsman and sociologist. The popular portrayal suggests there is a strong connection between his Highland background and his famous book An Essay on the History of Civil Society. It will be argued that this claim reproduces the social construction of space in Scottish society and is based on stereotypical views of his birthplace and upbringing. Ferguson did not construct an autobiographical narrative to offer his own understanding of the link between his life and work. This reflects the strengths and weaknesses of sociology as it was developing in the eighteenth century. The 'self' was not recognized as an object of intention or symbolic construction. Ferguson's writings analysed modernity as it was emerging in eighteenth-century Lowland Scotland and contrary to common opinion, there was no self-identity as a Highlander to shape his understanding of that social process. PMID- 17343641 TI - Dancing with the Devil? Essentialism and other feminist heresies. PMID- 17343657 TI - Association between diabetic microangiopathy and vascular endothelial function evaluated by flow-mediated vasodilatation in patients with type 2 diabetes. AB - The main purpose of the study was to investigate the association between vascular endothelial function and diabetic microangiopathy (nephropathy, retinopathy and neuropathy) in patients with type 2 diabetes. In addition, the association between endothelial function and macroangiopathy evaluated by intimal-medial complex thickness (IMT) was also investigated. Endothelial function was evaluated non-invasively by the measurement of flow-mediated vasodilatation (FMD) of the brachial artery. Diabetic nephropathy and neuropathy were assessed by urinary albumin excretion (UAE) and motor or sensory nerve conduction velocity (MCV, SCV), respectively, and retinopathy was evaluated by an ophthalmologist using the Davis classification. FMD was measured in 102 patients with type 2 diabetes and in 20 control subjects, and showed a tendency to be lower in the diabetic patients. There was a significant decrease in FMD in patients with proliferative diabetic retinopathy, compared with those in patients with no diabetic retinopathy. FMD showed significant positive correlations with MCV and SCV, and significant negative correlations with log UAE, systolic blood pressure and diabetic duration, but no correlation was obtained between FMD and IMT. In stepwise regression analysis, MCV alone showed a significant association with FMD. In conclusion, our results show that in patients with type 2 diabetes FMD is closely associated with all types of microangiopathy, with neuropathy being most strongly associated with FMD; however, FMD is not associated with macroangiopathy evaluated by IMT. PMID- 17343658 TI - Transcatheter arterial embolisation in anticoagulant-related haematoma--a current therapeutic option: a report of four patients and review of the literature. AB - The aim of this study is to present the computed tomography (CT) and angiographic findings of life-threatening extraperitoneal haemorrhage complicating anticoagulant therapy, treated with transcatheter arterial embolisation (TAE). CT and angiographic studies of four consecutive patients with large, extraperitoneal anticoagulant-related haematomas (ACH) treated by TAE were retrospectively reviewed. Attention was directed to the location of the haematoma and to the possible presence of active arterial extravasation on CT. Four women (mean age 70 years) with large extraperitoneal ACH's demonstrated on CT as extended rectus sheath haematoma in three and expanding iliopsoas haematoma in one, were successfully treated by TAE of the inferior epigastric (n=3) and lumbar artery (n=1). Two patients were diagnosed by contrast-enhanced CT as having active arterial bleeding within the haematoma requiring TAE. The other two were referred to angiography because of haemodynamic instability. We also reviewed the imaging findings of 26 patients with extraperitoneal ACH's requiring TAE described in the literature. In the reviewed cases, a female predominance was found, the retroperitoneum was the most frequent site and most patients recovered. To conclude, unenhanced CT has proved an excellent modality for the diagnosis of ACH's. TAE has been shown to be an effective and safe method for managing such haematomas when conservative treatment is insufficient. We suggest that whenever a large extraperitoneal ACH is seen on unenhanced CT, a subsequent contrast enhanced dynamic scan should be performed, unless contraindicated. Enhanced CT has a supplementary role in detecting active bleeding that provides an indication for angiographic therapy. Awareness of this optional treatment improve patient's outcome. PMID- 17343659 TI - Expression of the triggering receptor expressed on myeloid cells-1 mRNA in a heterogeneous infected population. AB - This study is to investigate the clinical utility of detection of peripheral blood triggering receptor expressed on myeloid cells (TREM)-1 mRNA as an early indicator of sepsis among critically ill patients and to compare the results of TREM-1 with those of C-reactive protein (CRP). A prospective, non-interventional study of 127 patients with at least two criteria of the systemic inflammatory response (SIRS) was performed. TREM-1 was assessed by real-time quantitative reverse transcription-polymerase chain reaction. The diagnosis of SIRS only was made in 41 patients (32%), and the diagnosis of sepsis was made in other 86 patients (68%). TREM-1 mRNA expression had the comparably discriminative value to differentiate the presence from the absence of infection, with an area under the receiver-operating characteristic curve (AUC) of 0.75 [95% confidence interval (95% CI), 0.67-0.84] than CRP [AUC, 0.72 (95% CI, 0.62-0.81)]. As an indicator of sepsis, a TREM-1 mRNA expression ratio cutoff value of 58.8 had a sensitivity of 72%, a specificity of 71%, a positive likelihood ratio of 2.5 and a negative likelihood ratio of 0.39. Furthermore, TREM-1 mRNA expression was selectively higher in septic patients caused by extracellular bacteria or fungi [112.4 (19.3 680.1)], than in those caused by intracellular bacteria or viruses [18.8 (7.6 53.0), p < 0.001]. There was no difference in plasma CRP levels between both septic groups (p = 0.782). TREM-1 and CRP are similar diagnostic markers of sepsis. The different ability of extracellular and intracellular pathogens to induce TREM-1 expression may provide a potential marker for differential diagnosis. PMID- 17343660 TI - Paliperidone: quo vadis? AB - Paliperidone, the 9-hydroxy metabolite of risperidone, was approved on 20 December, 2006 by the US Food and Drug Administration for the treatment of schizophrenia. It is also being tested for the treatment of bipolar mania. An on line query of http://www.pubmed.gov and http://www.clinicaltrials.gov for 'paliperidone' and '9-hydroxy-risperidone' was done, along with an examination of poster presentations at scientific meetings held in 2006. Three 6-week pivotal clinical trials of paliperidone extended-release at fixed doses ranging from 3 to 15 mg administered orally once daily in the treatment of acute schizophrenia demonstrated superior efficacy to placebo. A favourable tolerability profile was also evidenced, except for prolactin elevation and dose-related extra-pyramidal effects. A relapse prevention study provides evidence of superiority of paliperidone over placebo in the maintenance of response. Safety has also been assessed in patients with schizophrenia who are 65 years or older. At present there are no studies available that are powered to directly compare paliperidone to other second-generation antipsychotics, including risperidone. With the impending availability of oral risperidone as a generic medication, cost of oral paliperidone will likely become a significant obstacle to its use. PMID- 17343661 TI - Perceptions of service quality and sacrifice in patients with minor medical conditions using emergency care. AB - This study investigated the role of perceptions of service quality and sacrifice in patients attending the accident and emergency (A&E) departments with minor medical conditions that can be treated by their general practitioner (GP). Perceptions of service quality were measured using modified service quality performance indicators. Perceptions of monetary and non-monetary sacrifice were also captured. Questionnaire-based data were gathered prospectively through a random sample of adult patients who exhibited minor medical conditions at a UK teaching hospital A&E department. Service quality perceptions played a major part in the decision to attend A&E, whereas sacrifice perceptions did not. Perceptions of competence and credibility were the most important quality determinants and were rated higher for A&E than GP. Given that there were some misconceptions about the quality and nature of services each setting provides, recent reforms bringing about an ever-expanding range of healthcare service options may cause further confusion in patient decision-making. PMID- 17343662 TI - Does off-pump coronary artery bypass surgery reduce secretion of plasminogen activator inhibitor-1? AB - Prior studies showed that postoperative increase in plasminogen activator inhibitor-1 (PAI-1) levels is associated with an increased risk of graft occlusion after coronary artery bypass surgery (CABG). This prospective study aimed to compare the changes of PAI-1 antigen levels after off-pump and on-pump CABG. Forty-four patients admitted for elective CABG were randomised to on-pump (n=22) or off-pump (n=22) surgery. Serum samples were collected for estimation of PAI-1 and tissue plasminogen activator (t-PA) antigen levels preoperatively and 2 h after the operation. The groups were similar in terms of age, weight, gender ratio and extent of coronary disease, left ventricular function and number of grafts per patient. Fibrinogen and t-PA levels increased postoperatively in both the groups when compared with baseline values. After operation, statistical analysis revealed that increase of PAI-1 values was higher in off-pump group (44.1+/-9.1 vs. 25.3+/-6.9) than on-pump group (37.2+/-5.5 vs. 27.3+/-7.8, p=0.002). This study shows that increase in PAI-1 antigen values in patients who undergo off-pump (beating heart) CABG is significantly higher than in those who undergo conventional CABG with cardiopulmonary bypass. PMID- 17343663 TI - Caecal volvulus. PMID- 17343664 TI - Testosterone and ageing: what have we learned since the Institute of Medicine report and what lies ahead? AB - A 2003 report by the Institute of Medicine (IOM) surveyed the literature on the benefits and risks of testosterone replacement therapy in older men and identified knowledge gaps and research needs. This review summarises some key studies published since the IOM report. The possible relationship of testosterone to risk of prostate cancer remains a concern; however, no new evidence has emerged to suggest that testosterone replacement therapy increases the risk. Recent studies have demonstrated that hypogonadism in men may be more prevalent than previously thought, is strongly associated with metabolic syndrome, and may be a risk factor for type 2 diabetes and cardiovascular disease. Clinical studies have shown that testosterone replacement therapy in hypogonadal men improves metabolic syndrome indicators and cardiovascular risk factors. Maintaining testosterone concentrations in the normal range has been shown to contribute to bone health, lean muscle mass, and physical and sexual function, suggesting that testosterone replacement therapy may help to prevent frailty in older men. Based on current knowledge, testosterone replacement therapy is unlikely to pose major health risks in patients without prostate cancer and may offer substantial health benefits. Larger, longer-term randomised studies are needed to fully establish the effects of testosterone replacement therapy. PMID- 17343665 TI - Analysis of adrenal masses by 18F-FDG positron emission tomography scanning. AB - This study aimed to analyse the characteristics of adrenal masses visible in the computerised tomography (CT) scans which have been also evaluated by 2 [18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET), and to characterise the features of 18F-FDG PET scans associated with various adrenal endocrine tumours, especially benign functional tumours. 18F-FDG PET scans of 105 patients with adrenal masses on the CT scan were analysed. Positive uptakes in the 18F-FDG PET scans were seen in 60 malignant tumours (54 metastasic lesions, six primary adrenal cancers) and seven benign tumours. The positive predictive value of 18F-FDG PET imaging to characterise an adrenal mass as a malignant tumour was 90%; the corresponding negative predictive value to rule out malignancy was also 90%. Benign adrenal tumours were smaller than that of malignant lesions (p<0.05). The mean standardised uptake value max (SUVmax) of the metastatic lesions [8.4+/-6.5 (microCi/g)/microCi/kg] was significantly higher than that of the benign adrenal tumours [2.4+/-1.2 (microCi/g)/microCi/kg, p<0.001]. Examination of only the primary adrenal lesions revealed that all adrenocortical carcinomas, two of three cases of pheochromocytomas, three of five neuroblastomas and two of four cases of primary aldosteronism showed positive 18F FDG uptake. In conclusion, for patients presenting adrenal masses with a high probability of malignancy, 18F-FDG PET can be used to differentiate malignant from benign adrenal lesions. However, the 18F-FDG PET uptake did not show an always consistent pattern for endocrine tumours, which was probably due to the variability inherent in 18F-FDG uptake. This study suggests that 18F-FDG PET scanning can offer supporting data to localise and characterise adrenal tumours. PMID- 17343666 TI - Prognostic predictors of technique and patient survival in elderly Southeast Asian patients undergoing continuous ambulatory peritoneal dialysis. AB - The population of elderly patients entering chronic dialysis programmes is increasing. Elderly patients are susceptible to malnutrition and have multiple complicating disorders in addition to uraemia. Selecting appropriate dialysis modality is particularly critical in elderly patients. Continuous ambulatory peritoneal dialysis (CAPD) has many advantages to elderly patients; however, the clinical outcome varies for elderly CAPD patients. In comparison with Westerners, Southeast Asians have a small body mass index and may be more suited to CAPD therapy. To identify the prognostic predictors in elderly Southeast Asian patients, this historical cohort study analysed 144 patients aged > or = 65 years at initiation of CAPD. A group of haemodialysis (HD) patients aged > or = 65 years was utilised as the control group. Survival curves for patient and technique were derived from Kaplan-Meier analysis and were further analysed by Cox-Mantel log-rank test. To elucidate the impact of individual factors on patient survival, various significant univariables were further subjected to multivariate analysis. No significant increase existed for relative risk of technique failure in elderly patients compared with younger patients. This analytical data indicates that CAPD was as good as HD for elderly uraemic patients regarding to the patient survival. Diabetes, dependent patients, low albumin levels and previous HD history were significant poor prognostic factors for survival of elderly CAPD patients. In conclusion, CAPD is an effective modality of renal replacement therapy for Southeast Asian elderly patients. The technique survival was not affected by patient age. PMID- 17343667 TI - Helicobacter pylori-associated atrophic gastritis and carotid intima-media thickness: is there a link? AB - Chronic infections are associated with cardiovascular diseases. Helicobacter pylori-induced chronic active gastritis results in atrophic gastritis. In this study, we attempted to determine carotid intima-media thickness in patients with and individuals without H. pylori-induced atrophic gastritis. Oesophagogastroduodenoscopy was performed on 123 patients for various reasons. Helicobacter pylori were considered positive when histological examination and rapid urease test showed H. pylori. Helicobacter pylori-positive cases were divided into two groups, namely atrophic gastritis and non-atrophic gastritis. Of 123 patients, 92 patients had H. pylori-positive non-atrophic gastritis and 31 had H. pylori-positive atrophic gastritis. There was no significant difference in carotid intima-media thickness between the two groups. Carotid intima-media thickness is not associated with H. pylori-induced atrophic gastritis. PMID- 17343668 TI - Retrobulbar haemodynamic effects of the latanoprost/timolol and the dorzolamide/timolol fixed combinations in newly diagnosed glaucoma patients. AB - The objective of this study was to compare the effect of the latanoprost/timolol fixed combination (LTFC) and the dorzolamide/timolol fixed combination (DTFC) on the retrobulbar haemodynamic and intraocular pressure (IOP) in patents with open angle glaucoma (OAG). This was a prospective, examiner masked, randomised and crossover study. Participants were 32 consecutive subjects, who met the inclusion/exclusion criteria, with newly diagnosed OAG. Patients were randomised to either LTFC or DTFC for the first 1-month treatment phase after a 1-month washout period, without medical treatment, patients began with the opposite treatment for the second 1-month treatment period. Colour Doppler parameters in ophthalmic artery (OA) and posterior ciliary arteries (PCA), ocular perfusion pressure, IOP and systemic haemodynamics were assessed at each baseline and at the end of each treatment period. The main outcomes include peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) in OA and PCA. DTFC significantly increased EDV in OA from 7.55 (1.16) to 9.32 (1.22), p<0.0001, and in the PCA from 4.41 (0.70) to 5.36 (0.60), p<0.0001, and significantly decreased RI in OA from 0.775 (0.036) to 0.725 (0.032), p<0.0001, and in the PCA from 0.694 (0.045) to 0.634 (0.034). LTFC significantly decreased the EDV and significantly increased RI in PCA, p=0.0076 and p=0.0009, respectively. There were no statistical significant differences in the IOP lowering effect between both treatments. DTFC seems to have a beneficial vascular effect on retrobulbar vessels in OAG patients. PMID- 17343669 TI - Positioning a safe gastric puncture point before percutaneous endoscopic gastrostomy. AB - To position a safe gastric puncture point prior to the percutaneous endoscopic gastrostomy (PEG) a technique using an abdominal plain film with a gastric insufflation was assessed. After insufflated with 500 ml of air, an abdominal plain film was obtained before PEG in 84 patients. The body of the stomach near the angularis, equidistant from the greater and lesser curves, was defined as the optimal gastric puncture point. The location of the puncture points varied greatly, being situated over the right upper quadrant in 31% of patients, left upper in 59%, right lower in 5% and left lower quadrant in 5% of patients. The marked puncture points on abdominal film in some patients were shown to be partially covered by colon or small bowel loop, lie high under the costal margin, or low beneath the umbilicus. An abdominal plain film utilising a gastric insufflation technique prior to PEG may help to determine optimal gastric puncture site selection. Use this technique in clinical practice might hasten procedural time, provide better assurance to the clinical doctor, and provide an added margin of safety for the patient. PMID- 17343670 TI - Effect of Helicobacter pylori infection and eradication therapy on interleukin-6 levels in patients with Familial Mediterranean Fever. AB - It is being questioned if Helicobacter pylori infection, which causes a chronic inflammatory response, can increase the frequency and severity of attacks in patients with Familial Mediterranean Fever (FMF) and if the impact of inflammatory response can be diminished by eradication of the infection. To evaluate if there is difference in interleukin (IL)-6 levels of H. pylori positive and -negative patients both before and during FMF attacks; if there is a change in IL-6 levels following successful eradication treatment; and if MEFV gene mutations have an effect on IL-6 levels. IL-6 levels were evaluated in 47 FMF patients before and during FMF attacks. Genetic testing to determine M694V, M694I, E148Q, V726V, M680I mutations was also performed in all patients. IL-6 levels were also determined after successful eradication of the infection in H. pylori-positive patients. IL-6 levels were compared in H. pylori-positive and negative patients, and before and after eradication treatment in patients who cleared the infection. Number of patients in tested mutation groups was not enough to compare IL-6 levels in these groups. Thirty-four patients (73.9%) were H. pylori-positive. Before FMF attack there was no statistically significant difference in IL-6 levels of H. pylori-positive and -negative groups. IL-6 levels were significantly higher in both groups during the attacks than before the attacks (p < 0.05). There was a statistically significant decline in IL-6 levels both before and during FMF attacks, following eradication therapy in patients who cleared the infection (p < 0.05). In patients with homozygous M694V mutation, IL 6 levels before and during the FMF attacks were not significantly different in H. pylori-positive and -negative groups, despite a much lower level found in H. pylori-negative group (p > 0.05). Comparisons were not performed in other mutation groups because of small number of patients in each group. C-reactive protein (CRP) and fibrinogen levels were not significantly different between the groups (p > 0.05). We believe that the observation of IL-6 levels are lower both before and during FMF attacks both in H. pylori-negative patients and in patients who cleared the infection after eradication therapy is very important in the determination of the role of eradication of H. pylori on decreasing the frequency and severity of FMF attacks. As for today, the correlation between H. pylori infection and FMF seems unlikely; however, studies evaluating the interaction of cytokines in both diseases and their relations and roles will be needed to reach better conclusions. PMID- 17343671 TI - Brucella melitensis in the aetiology of febrile neutropenia: report of two cases brucellosis and febrile neutropenia. PMID- 17343672 TI - Effects of music on gastric myoelectrical activity in healthy humans. AB - The aim was to study the effects of listening to music on gastric myoelectrical activity in healthy humans. Gastric myoelectrical activity was recorded using surface electrogastrography from 17 healthy volunteers before and for 30 min after they listened to music. All subjects listened to the same music. Ten perceived the music as enjoyable and seven did not. The percentages of normal slow wave, dominant frequency and dominant power did not differ significantly between baseline and during music intervention. An analysis of covariance model that included the subjects' feelings about the music and dominant power showed significantly higher dominant power during music intervention in subjects who enjoyed the music (p < 0.01). In the individuals who enjoyed the music, dominant power (55.0 +/- 9.2 dB) was significantly higher during music intervention than at baseline (49.5 +/- 6.8 dB, p = 0.03). In the subjects who did not enjoy the music, dominant power was significantly lower during music intervention than at baseline (48.8 +/- 6.8 and 55.7 +/- 6.2 dB, respectively; p < 0.01). Listening to enjoyable music increases the amplitude of gastric myoelectrical activity in healthy humans. Music therapy may improve gastric motility and may be used to stimulate gastric emptying. PMID- 17343673 TI - Bartonella henselae lymphadenitis progressing to hepatosplenic disease with slow clinical response despite early diagnosis and treatment. PMID- 17343674 TI - Acute myocardial infarction in young patients: the culprit is not always a ruptured atherosclerotic plaque. PMID- 17343675 TI - Avirulence proteins from haustoria-forming pathogens. AB - A major insight that has emerged in the study of haustoria-forming plant pathogens over the last few years is that these eukaryotic biotrophs deliver suites of secreted proteins into host cells during infection. This insight has largely derived from successful efforts to identify avirulence (Avr) genes and their products from these pathogens. These Avr genes, identified from a rust and a powdery mildew fungus and three oomycete species, encode small proteins that are recognized by resistance proteins in the host plant cytoplasm, suggesting that they are transported inside plant cells during infection. These Avr proteins probably represent examples of fungal and oomycete effector proteins with important roles in subverting host cell biology during infection. In this respect, they represent a new opportunity to understand the basis of disease caused by these biotrophic pathogens. Elucidating how these pathogen proteins gain entry into plant cells and their biological function will be key questions for future research. PMID- 17343676 TI - Efficient downregulation of alb1 gene using an AMA1-based episomal expression of RNAi construct in Aspergillus fumigatus. AB - An episomal RNAi silencing construct containing the inducible cbhB promoter and a hairpin structure has been made to downregulate the alb1 gene in the human pathogen Aspergillus fumigatus. Transformation of fungal protoplasts resulted in a high number of transformants with an inducible silenced phenotype (white spores). Efficient downregulation of the alb1 gene using this system suggests that this approach may overcome the variable downregulation observed with integrative constructs. PMID- 17343677 TI - Efficient silencing of the gene coding for the epsilon subunit of DNA polymerase III in Escherichia coli is triggered by antisense RNAs featuring stability in vivo. AB - The Escherichia coli gene dnaQ coding for the epsilon subunit of DNA polymerase III was suppressed in vivo via antisense RNAs. To this aim, different fragments of dnaQ were cloned in reverse orientation into the pBAD-HisB vector or into pT3T7, and the corresponding antisense RNAs were conditionally expressed in vivo. Antisense transcripts featuring fast hybridization in vitro with dnaQ mRNA but lacking stability in vivo did not suppress the target gene. Moreover, the in vivo concentration of an antisense transcript was positively correlated to its silencing effectiveness. PMID- 17343678 TI - The contribution of induction of temperate phages to the numbers of free somatic coliphages in waters is not significant. AB - Somatic coliphages have been proposed as indicators of water quality. But several factors have been considered a drawback for their use as indicators. We evaluated the contribution of temperate phages to the numbers of somatic coliphages detected in water by ISO (International Standards Organization) standardised methods. Prophage induction from naturally occurring bacteria was assayed with mitomycin C, ciprofloxacin and UV irradiation. Results indicate that the presence of prophages will not influence the determinations of somatic coliphages in water. PMID- 17343679 TI - Effect of primer mismatch, annealing temperature and PCR cycle number on 16S rRNA gene-targetting bacterial community analysis. AB - In the attempt to explore complex bacterial communities of environmental samples, primers hybridizing to phylogenetically highly conserved regions of 16S rRNA genes are widely used, but differential amplification is a recognized problem. The biases associated with preferential amplification of multitemplate PCR were investigated using 'universal' bacteria-specific primers, focusing on the effect of primer mismatch, annealing temperature and PCR cycle number. The distortion of the template-to-product ratio was measured using predefined template mixtures and environmental samples by terminal restriction fragment length polymorphism analysis. When a 1 : 1 genomic DNA template mixture of two strains was used, primer mismatches inherent in the 63F primer presented a serious bias, showing preferential amplification of the template containing the perfectly matching sequence. The extent of the preferential amplification showed an almost exponential relation with increasing annealing temperature from 47 to 61 degrees C. No negative effect of the various annealing temperatures was observed with the 27F primer, with no mismatches with the target sequences. The number of PCR cycles had little influence on the template-to-product ratios. As a result of additional tests on environmental samples, the use of a low annealing temperature is recommended in order to significantly reduce preferential amplification while maintaining the specificity of PCR. PMID- 17343680 TI - The plasma membrane calcium ATPase MCA-3 is required for clathrin-mediated endocytosis in scavenger cells of Caenorhabditis elegans. AB - Plasma membrane Ca2+ ATPases (PMCAs) maintain proper intracellular Ca2+ levels by extruding Ca2+ from the cytosol. PMCA genes and splice forms are expressed in tissue-specific patterns in vertebrates, suggesting that these isoforms may regulate specific biological processes. However, knockout mutants die as embryos or undergo cell death; thus, it is unclear whether other cell processes utilize PMCAs or whether these pumps are largely committed to the control of toxic levels of calcium. Here, we analyze the role of the PMCA gene, mca-3, in Caenorhabditis elegans. We report that partial loss-of-function mutations disrupt clathrin mediated endocytosis in a class of scavenger cells called coelomocytes. Moreover, components of early endocytic machinery are mislocalized in mca-3 mutants, including phosphatidylinositol-4,5-bisphosphate, clathrin and the Eps15 homology (EH) domain protein RME-1. This defect in endocytosis in the coelomocytes can be reversed by lowering calcium. Together, these data support a function for PMCAs in the regulation of endocytosis in the C. elegans coelomocytes. In addition, they suggest that endocytosis can be blocked by high calcium levels. PMID- 17343681 TI - Regulation of phagocytosis in Dictyostelium by the inositol 5-phosphatase OCRL homolog Dd5P4. AB - Phosphoinositides are involved in endocytosis in both mammalian cells and the amoeba Dictyostelium discoideum. Dd5P4 is the Dictyostelium homolog of human OCRL (oculocerebrorenal syndrome of Lowe); both have a RhoGAP domain and a 5 phosphatase domain that acts on phosphatidylinositol 4,5 bisphosphate/phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). Inactivation of Dd5P4 inhibits growth on liquid medium and on bacteria. Dd5p4-null cells are impaired in phagocytosis of yeast cells. In wild-type cells, PI(3,4,5)P3 is formed and converted to PI(3,4)P2 just before closure of the phagocytic cup. In dd5p4-null cells, a phagocytic cup is formed upon contact with the yeast cell, and PI(3,4,5)P3 is still produced, but the phagocytic cup does not close. We suggest that Dd5P4 regulates the conversion of PI(3,4,5)P3 to PI(3,4)P2 and that this conversion is essential for closure of the phagocytic cup. Phylogenetic analysis of OCRL-like 5-phosphatases with RhoGAP domains reveal that D. discoideum Dd5P4 is a surprisingly close homolog of human OCRL, the protein responsible for Lowe syndrome. We expressed human OCRL in dd5p4-null cells. Growth on bacteria and axenic medium is largely restored, whereas the rate of phagocytosis of yeast cells is partly restored, indicating that human OCRL can functionally replace Dictyostelium Dd5P4. PMID- 17343682 TI - Interaction of Arcobacter spp. with human and porcine intestinal epithelial cells. AB - Little is known about the pathogenic mechanisms or potential virulence factors of Arcobacter spp. The aim of the study described here was to obtain more insights in the pathogenicity mechanisms of Arcobacter spp. by testing their ability to adhere to, invade and induce interleukin-8 expression in human Caco-2 and porcine IPI-2I cell lines. Eight Arcobacter strains were tested. Four strains were obtained from a culture collection, and represent the four Arcobacter spp. known to be associated with animals and humans. The other four strains were field isolates from the amniotic fluid of sows and from newborn piglets. All eight Arcobacter strains were able to adhere to both cell lines, and induced interleukin-8 production as early as 2 h after a 1h incubation period. This production was still increased 6 h postinfection. Differences in the cell association of the eight strains were obvious, with A. cibarius showing the highest adhesion ability. Invasion of intestinal epithelial cells was only observed for A. cryaerophilus strains. No correlation between invasiveness or strong adhesion of the tested strains and the level of interleukin-8 induction was observed. PMID- 17343683 TI - T-cell signaling pathways inhibited by the tick saliva immunosuppressor, Salp15. AB - The Ixodes scapularis salivary protein Salp15 inhibits the activation of T cells through its interaction with the coreceptor CD4. Salp15 prevents the activation of Lck upon TCR engagement and the formation of lipid rafts. We have now analyzed the signaling pathways that are inhibited by the tick salivary protein in CD4(+) T cells. Salp15 affects tyrosine phosphorylation of several early signal components downstream of Lck, including LAT and Vav1, which results in improper actin polymerization. The effect of Salp15 is due to its interaction with CD4, as no effect was observed in CD4-negative T cells. Finally, we demonstrate that the peptide that mediates the interaction of Salp15 with CD4, P11, is able to recapitulate the immunosuppressive activity of the whole protein. These results clarify the molecular mechanisms of action of Salp15 on T cells and suggest that binding to CD4 is sufficient to elicit its immunosuppressive effect. PMID- 17343685 TI - Malignancies of the colorectum and anus in solid organ recipients. AB - Patients undergoing solid organ transplantation (SOT) are at increased risk for developing malignancies due to the long term immunosuppression. Data on malignancies of the large intestine after various types of SOT are rare. A total of 3595 SOTs were performed between 1986 and 2005 at our center and retrospectively analyzed with regard to the incidence and course of malignancies of the colon, rectum, and anus. Standard immunosuppression consisted of calcineurin inhibitors in combination with azathioprine or mycophenolate mofetil and steroids with or without antithymocyte globulin or IL-2 receptor antagonist induction. A total of 206 patients (5.7%) developed malignancies. Colorectal adenocarcinoma was diagnosed in nine patients (0.25%; mean age at diagnosis 65 years) at a mean of 5.3 years after transplantation. Five patients (55%) died 7.2 years post-transplant due to cardiovascular disease (n = 4) and tumor progression (n = 1). Four patients developed anal neoplasia (0.11%) 7 years post-transplant with 100% 1-year survival. Five patients showed post-transplant lymphoproliferative disorders (PTLD) with intestinal involvement. The incidence of anal but not of colorectal cancers in our transplant recipients differed from that of immunocompetent individuals of corresponding age (0.11% vs. 0.002% and 0.25% vs. 0.3%). PTLD may involve the colon. PMID- 17343684 TI - Inactivation of a subpopulation of human neutrophils by exposure to ultrahigh molecular-weight polyethylene wear debris. AB - Polymorphonuclear neutrophils, a first line of defence against invading microbial pathogens, may be attracted by inflammatory mediators triggered by ultrahigh molecular-weight polyethylene (UHMWPE) wear particles released from orthopaedic prostheses. Phagocytosis of UHMWPE particles by neutrophils may indirectly compromise their phagocytic-bactericidal mechanisms, thus enhancing host susceptibility to microbial infections. In an in vitro assay, pre-exposure of purified human neutrophils to UHMWPE micrometre- and submicrometre-sized wear particles interfered with subsequent Staphylococcos aureus uptake in a heterogeneous way, as assessed by a dual label fluorescence microscopic assay that discriminated intracellular rhodamine-labelled UHMWPE particles from fluorescein isothiocyanate-labelled S. aureus. Indeed, a higher percentage (44%) of neutrophils having engulfed UHMWPE particles lost the ability to phagocytize S. aureus, compared with UHMWPE-free neutrophils (<3%). Pre-exposure of neutrophils to UHMWPE wear particles did not impair but rather stimulated their oxidative burst response in a chemoluminescence assay. The presence of UHMWPE wear particles did not lead to significant overall consumption of complement mediated opsonic factors nor decreased surface membrane display of neutrophil complement receptors. In conclusion, engulfment of UHMWPE wear particles led to inactivation of S. aureus uptake in nearly half of the neutrophil population, which may potentially impair host clearance mechanisms against pyogenic infections. PMID- 17343686 TI - Short-term versus long-term induction therapy with antithymocyte globulin in orthotopic liver transplantation. AB - T-cell depletion is an essential aspect of clinical immunosuppression. The aim of the present study was to compare the efficacy of two dosage regimens in this setting. We retrospectively compared 246 patients (group 1) who received a 10-day antithymocyte globulin (ATG) induction protocol with 226 patients (group 2) who received a 3-day protocol. The 6-month rejection rate was 22.3% in group 1 and 12.7% in group 2 (P = 0.03). The sub-analysis showed a higher rejection rate in patients with cholestatic disease (P = 0.01), who were more numerous in group 1. This resulted in an overall difference between the groups. Rates of de novo malignancies and recurrent hepatocellular carcinoma were identical. Viral infection rates were 16% and 18%, respectively (P > 0.5). The rates of bacterial and fungal infection were also similar (37% vs. 42%, P > 0.1). However, infection and ATG administration are independent risk factors for survival. A lower rate of fatal infection was observed in group 2 (P = 0.01), while the 10-day ATG regimen had a detrimental effect on patients who had infection (P < 0.0001). Our results strongly support the application of 3-day ATG induction therapy regimen after orthotopic liver transplantation, as it is associated with the same rejection rate as long-term ATG induction therapy, without the negative survival effect of the latter due to lethal infection. PMID- 17343687 TI - Outcomes after identical and compatible orthotopic liver transplantation for fulminant hepatic failure: a single center experience in UK. AB - To analyze the outcomes between identical and compatible liver transplantation (OLT) for fulminant hepatic failure (FHF) from September 1984 to November 2005. The patients were divided in three groups; group 1 (identical), group 2 (compatible) and group 3 (incompatible), according to the donor-recipient blood type matching. We analyzed several outcomes regarding mortality, patient and graft survival, incidence of acute graft rejection during the first postoperative month (30 days), incidence of biliary complications and indications of re transplantation. We also analyzed the relationship of Coomb's positive test with postoperative hemolysis to all the above mentioned factors. During the study period, 168 males and 112 females underwent their first OLT for FHF, with 37.1% overall mortality and 42.1% overall graft failure rate. The results between group 1 (203 patients) and group 2 (73 patients) were comparable. A statistically significant difference was recorded in 1 year and overall graft survival between group 1 and group 2 (P = 0.049 and log-rank = 0.035 respectively). Coomb's positive test did not influence the outcomes. OLT in FHF can be safely carried out whether the donor organs are identical or compatible. Hemolysis (Coomb's positive test) after identical or compatible OLT does not influence the outcomes. PMID- 17343688 TI - The genus Lactobacillus--a genomic basis for understanding its diversity. AB - The genus Lactobacillus is a diverse group that includes many species used in food production and preservation. Some lactobacilli are considered probiotic, conferring health benefits upon the host. The heterogeneity of this genus poses challenges and opportunities when characterizing or exploiting individual strains. To date, 10 Lactobacillus genome sequences have been published, and at least 11 more sequencing projects are ongoing. These studies will dramatically improve one's understanding of metabolic processes, bioprocessing capabilities and potential roles in health and well-being of the Lactobacilli. This review describes the current status of Lactobacillus genome sequence projects, highlights the major findings and summarizes functional genomics or comparative genomics studies. The genomic basis for the unusual diversity of this genus is discussed, and the potential for comparative genomics to rigorously extend phylogenetic analysis of the Lactobacilli is described. PMID- 17343689 TI - Rapid identification of Escherichia coli safety and laboratory strain lineages based on Multiplex-PCR. AB - Escherichia coli K-12, B, C and W strains are the most frequently used bacterial safety and laboratory strains. Lineage-specific DNA fragments were detected by microplate subtractive hybridization and utilized to create a fast differentiation method using a single PCR reaction to differentiate clearly the four lineages and separate them from pathogenic variants. The method has been evaluated on a comprehensive selection of widely used laboratory strains and a variety of pathogenic E. coli representatives. In addition, in silico analysis on all available E. coli genomes and the genomes of the close relatives Shigella and Salmonella confirmed the reliability of the proposed method. A fast identification and differentiation of E. coli safety strains by Multiplex-PCR is a useful tool for researchers and companies to check and monitor their reference stocks. PMID- 17343690 TI - Glaucoma detection using different Stratus optical coherence tomography protocols. AB - PURPOSE: To examine and compare the diagnostic accuracy of retinal nerve fibre layer (RNFL) thickness measurements using different Stratus optical coherence tomography (OCT) scanning protocols. METHODS: Stratus OCT data for 90 healthy subjects and 62 glaucoma patients with mild or moderate visual field loss were prospectively collected and analysed using four RNFL thickness protocols that differed in terms of image resolution and number of scans. Cut-off levels corrected for age and refractive error were defined by reference values derived from an independent normal database. Sensitivity and specificity were calculated for average RNFL thickness for the full circle scan, and for the quadrant and clock hour circle scan sectors at p < 5% and p < 1% cut-off values. RESULTS: Regular- and high-resolution images performed equally well, and single best quality scans were as good as the average of three scans to distinguish between healthy and glaucomatous eyes. Full circle RNFL thickness yielded similar or better diagnostic accuracy than that of sectors. Sensitivities ranged from 84% to 87% and specificities from 89% to 93% for full circle RNFL thickness at the p < 5% cut-off level. CONCLUSIONS: The abilities of four different Stratus OCT RNFL thickness protocols to distinguish between eyes with predominantly mild glaucomatous field loss and healthy eyes were very similar. Thus diagnostic accuracy did not differ between high- and regular-resolution protocols, nor between global (full circle) and localized (sector) OCT parameters, which suggests a diffuse component in early glaucomatous RNFL damage. PMID- 17343692 TI - Recognition of pixelized Chinese characters using simulated prosthetic vision. AB - The rehabilitation of the reading ability of the blind with a limited number of stimulating electrodes is regarded as one of the major functions of the envisioned visual prosthesis. This article systematically studied how many pixels of individual Chinese characters should be needed for correct and economic recognition by blind Chinese subjects. In this study, 40 normal-sighted subjects were tested on a self-developed platform HanziConvertor (Institute for Laser Medicine & Bio-photonics, Shanghai Jiaotong University, China) with digital imaging processing capacities to convert images of printed text into various pixelized patterns made up of discrete dots, and present them orderly on a computer screen. It was found that various complicated factors such as pixel number, character typeface, stroke number, etc., can obviously affect the recognition accuracy. It was also found that optimal recognition accuracy occurs at a specific size of binary pixel array, due to a trade-off between a strictly limited number of stimulation electrodes and character sampling resolution. The results showed that (i) recognition accuracy of pixelized characters is optimal with at least 12 x 12 binary pixels, and therefore it is recommended to apply a minimum of 150 discrete and functioning electrodes for restoring the reading ability of blind Chinese individuals in the visual prosthesis; (ii) fonts of Song Ti and Hei Ti are clearer and more effective than other typefaces; and (iii) characters with fewer strokes lead to better accuracy. PMID- 17343693 TI - In vivo cartilage tissue engineering using a cell-derived extracellular matrix scaffold. AB - We have observed in our previous study that a cell-derived extracellular matrix (ECM) scaffold could assure the growth of a cartilage tissue construct in vitro. The purpose of the present study was to evaluate the feasibility of a chondrocyte seeded cell-derived ECM scaffold by implanting it in vivo in nude mouse. A porous cell-derived ECM scaffold was prepared with a freeze-drying protocol using porcine chondrocytes. Rabbit articular chondrocytes were seeded onto the scaffold and cultured for 2 days in vitro, and then implanted into the nude mouse subcutaneously. They were retrieved at 1, 2, and 3 weeks postimplantation. Under macroscopic analysis, the cartilage-like tissue formation matured with time and developed a smooth, white surface. Contrary to the control (in which no cells were seeded), the size of the neocartilage tissue increased slightly by the third week and remained more stable. Total glycosaminoglycan (GAG) content and the GAG/DNA ratio increased significantly with time in the chemical analysis. The histology exhibited a sustained accumulation of newly synthesized sulfated proteoglycans. Immunohistochemistry, Western blot, and reverse transcriptase polymerase chain reaction (RT-PCR) clearly identified type II collagen at all time points. Compressive strength of in vivo neocartilage increased from 0.45 +/- 0.06 MPa at 1 week to 1.18 +/- 0.17 MPa at 3 weeks. In conclusion, this study demonstrated that the cell-derived ECM scaffold could provide chondrocytes with favorable in vivo environment to produce a hyaline-like cartilage tissue. PMID- 17343694 TI - Anticoagulation minimization is safe and effective in albumin liver dialysis using the molecular adsorbent recirculating system. AB - The molecular adsorbent recirculating system (MARS) is a blood purification device with renal and hepatic dialytic effects. This study examined the use of low-dose unfractionated heparin in MARS. This was a prospective, observational study of 15 MARS treatment sessions (mean duration per treatment cycle = 12.2 +/- 4.5 h) in four patients with severe acute decompensation of chronic liver disease (n = 3) and fulminant hepatic failure (n = 1) treated with intermittent MARS. All patients were critically ill (APACHE II 24.8 +/- 3.3). Renal dialysis was with continuous hemofiltration and/or slow low-efficiency dialysis. One MARS session was terminated because of vascular access occlusion (1/15; 6.7%). Bleeding was noted in two sessions (2/15; 13%). Twelve MARS sessions were heparin-free and three treatments were with mean heparin dose of 833 +/- 382 IU. Serum biochemical parameters pre- and post-MARS were total bilirubin (micromol/L): 409.4 +/- 141.6 versus 282.9 +/- 90, P < 0.05; plasma ammonia (micromol/L): 44.3 +/- 21.2 versus 28.8 +/- 20.2, P = 0.002; urea (mmol/L): 15.9 +/- 11.8 versus 7.9 +/- 6.6, P = 0.002; creatinine (micromol/L): 252.4 +/- 151.9 versus 150.1 +/- 96.6, P = 0.003. Pre-MARS versus post-MARS systolic (SBPs) and diastolic (DBPs) blood pressures (mm Hg) were SBP = 129.2 +/- 27.7 versus 124 +/- 25, P = 0.838; and DBP = 60.7 +/ 15.3 versus 56 +/- 13, P = 0.595. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count (Plt) pre- and post-MARS were PT(s): 22 +/- 7.9 versus 23.8 +/- 10.2, P = 0.116; aPTT (s): 64.5 +/- 40.9 versus 85.5 +/- 50.6, P = 0.092; and Plt (x10(3)/mm(3)): 87 +/- 67.6 versus 68.8 +/- 39, P = 0.098. MARS priming with heparin saline was safe. Heparin-minimized MARS did not compromise circuit function and longevity in extended intermittent MARS. PMID- 17343695 TI - Citrate anticoagulation control by ionized calcium levels does not prevent hemostasis and complement activation during hemodialysis. AB - The purpose of this study was to determine whether or not regional citrate anticoagulation (RCA) controlled by ionized calcium (iCa(2+)) would overcome thrombogenicity, prevent hemostasis, and complement activation during hemodialysis (HD). RCA was performed in 10 patients during 10 HD sessions using a polysulfone membrane in an effort to keep iCa(2+) at dialyzer outlet at < or =0.4 mmol/L. Compared to baseline, plasma levels of thrombin-antithrombin III complexes rose significantly at 240 min, and tissue factor and complement C5a component levels at 30 and 240 min of the procedure. Thrombocyte count declined significantly at 30 and 240 min, while activated clotting time (ACT) did not increase significantly, and platelet factor 4 as well as von Willebrand factor levels did not alter significantly. While ACT correlated significantly with some thrombogenicity markers, iCa(2+) did not correlate with ACT, changes in hemostasis, or C5a. We conclude the usually recommended iCa(2+) levels in the HD extracorporeal circuit did not guarantee the complete overcoming of thrombogenicity, prevention of hemostasis, and complement activation. PMID- 17343696 TI - Biocompatibility of a novel avidin-agarose adsorbent for extracorporeal removal of redundant radiopharmaceutical from the blood. AB - The use of monoclonal antibodies (MAbs) in cytotoxic conjugates (radionuclides, toxins, or drugs) for targeting tumor cells is restricted due to toxicity in vital organs. Through improved tumor targeting, it is possible to administer larger amounts of such labeled MAbs, thus improving the ability to eradicate tumor cells without increased normal organ toxicity. Extracorporeal affinity adsorption treatment (ECAT) has therefore been developed using an avidin-agarose (AA) adsorbent with high binding affinity for the biotinylated radiolabeled MAb, rituximab. During ECAT, excess radioimmunoconjugates, not bound to the tumor cells, can be removed improving tumor targeting. The present study was performed to estimate the biocompatibility of the AA adsorber. Seven patients with B-cell lymphoma not responding to conventional treatment were studied. During the ECAT procedure, blood (B) components, plasma (P) complement fragments C3a, C5a, and P bradykinin were analyzed, and other laboratory tests were carried out. Slight decreases in B-hemoglobin (8.3%), B-thrombocytes (11.4%), and P-albumin (14.3%) were observed, and could be explained by the dilution of the blood with normal saline and acid citrate dextrose. The AA adsorbent had no effect on the blood cells, immunological status or P-bradykinin level. The AA adsorber demonstrated good hemocompatibility and biocompatibility, without any side effects in the patients. PMID- 17343697 TI - A new minimized perfusion circuit provides highly effective ultrasound controlled deairing. AB - Minimized perfusion circuits (MPCs) have been criticized for insufficient air elimination. The deairing capabilities of a new MPC, including an ultrasound controlled deairing unit, were compared to a standard extracorporeal circuit (ECC) in a laboratory setup. During blood flow of 4.0l/min, we injected 30-cc air over a period of 30 s into the venous line of both systems (n = 10 measurements/15-min intervals). Air was detected during the first 2 min post injection using a dual-channel ultrasound bubble counter. Venous air bubble measurements were made after the MPC bubble trap and the ECC hard-shell reservoir, respectively. Arterial air bubble data were obtained after the arterial filters (40 microm). Venous bubble count was significantly (P < 0.01) reduced in the MPC group (5-250 microm, 681 +/- 177; >40 microm, 288 +/- 92) compared with the ECC group (5-250 microm, 19 272 +/- 682; >40 microm, 7642 +/- 520). After the arterial filter, minimal numbers of air bubbles (5-250 microm, 172 +/- 59; >40 microm, 0) could be detected in the MPC group, but large amounts of air (5-250 microm, 16 194 +/- 1072; >40 microm, 3732 +/- 997) were measured in the ECC group. The air elimination of the modern MPC is superior to conventional ECC, which may result in a reduction of neurological complications. PMID- 17343698 TI - A hydrodynamically suspended, magnetically sealed mechanically noncontact axial flow blood pump: design of a hydrodynamic bearing. AB - To overcome the drive shaft seal and bearing problem in rotary blood pumps, a hydrodynamic bearing, a magnetic fluid seal, and a brushless direct current (DC) motor were employed in an axial flow pump. This enabled contact-free rotation of the impeller without material wear. The axial flow pump consisted of a brushless DC motor, an impeller, and a guide vane. The motor rotor was directly connected to the impeller by a motor shaft. A hydrodynamic bearing was installed on the motor shaft. The motor and the hydrodynamic bearing were housed in a cylindrical casing and were waterproofed by a magnetic fluid seal, a mechanically noncontact seal. Impeller shaft displacement was measured using a laser sensor. Axial and radial displacements of the shaft were only a few micrometers for motor speed up to 8500 rpm. The shaft did not make contact with the bearing housing. A flow of 5 L/min was obtained at 8000 rpm at a pressure difference of 100 mm Hg. In conclusion, the axial flow blood pump consisting of a hydrodynamic bearing, a magnetic fluid seal, and a brushless DC motor provided contact-free rotation of the impeller without material wear. PMID- 17343699 TI - Artificial Organs 2006: a year in review. PMID- 17343701 TI - Chest pain is inversely associated with blood pressure during exercise among individuals being assessed for coronary heart disease. AB - Acute and chronic increases in blood pressure have been related to decreases in pain perception. This phenomenon has been studied primarily using acute experimental pain stimuli. To extend the literature to naturalistic pain and in particular the problem of silent cardiac ischemia, this study examined the relationship between blood pressure and chest pain during exercise stress testing. Nine hundred seven (425 men, 482 women) individuals undergoing exercise stress testing for diagnosis of possible myocardial ischemia completed the McGill Pain Questionnaire (MPQ) immediately afterward and other questionnaires before and after testing. Blood pressure was measured before, during, and after exercise. Systolic blood pressure at the end of exercise was inversely related to a number of measures of pain such as total score on the MPQ. The relationship could not be explained by individual differences in exercise duration, medication use, sex, or other measured variable. In sum, the inverse relationship between blood pressure and sensitivity to pain that has been observed in other populations in experimental and naturalistic conditions was observed for chest pain during exercise. Blood pressure may contribute to episodes of silent ischemia. PMID- 17343702 TI - Validation of sternal skin conductance for detection of hot flashes in prostate cancer survivors. AB - The gold standard for objectively measuring hot flashes in women is an increased sternal skin conductance level (SCL), but validation studies in prostate cancer patients are lacking. In the laboratory, an SCL increase of > or = 1.78 micro-mho in 45 s had a sensitivity of 68% and a positive predictive value of 100% in detecting self-reported hot flashes among prostate cancer patients. Outside the laboratory, 71% of the objective markers of hot flashes were accompanied by a subjective report of a hot flash, and 65% of subjective reports occurred in the absence of an objective criterion. This study demonstrates that sternal skin conductance can be used to detect hot flashes in men in a manner analogous to its utilization among women. Such use would improve outcome analysis of treatment studies. PMID- 17343703 TI - Interoceptive sensitivity and physical effort: implications for the self-control of physical load in everyday life. AB - This study examined the relationship between interoceptive sensitivity and the behavioral self-regulation of physical load. According to their performance in a heartbeat detection task, 34 participants were classified as good or poor heartbeat perceivers. Participants pedaled on a bicycle ergometer for 15 min and were free to choose the tempo of their cycling. Good heartbeat perceivers covered a significantly shorter distance and showed a significantly smaller increase in mean heart rate, stroke volume, and cardiac output. There were significant negative correlations between heartbeat perception score and covered distance, changes in heart rate, changes in stroke volume, and changes in cardiac output. These results were not explained by differences in physical fitness level (PWC150). The findings suggest that good heartbeat perceivers show a more finely tuned behavioral self-regulation of physical load than poor heartbeat perceivers. PMID- 17343704 TI - Comparison of time and frequency domain measures of RSA in ambulatory recordings. AB - The extent to which various measures of ambulatory respiratory sinus arrhythmia (RSA) capture the same information across conditions in different subjects remains unclear. In this study the root mean square of successive differences (RMSSD), peak valley RSA (pvRSA), and high frequency power (HF power) were assessed during ambulatory recording in 84 subjects, of which 64 were retested after about 3 years. We used covariance structure modeling to test the equality of the correlations among three RSA measures over two test days and three conditions (daytime sitting or walking and nighttime sleep) and in groups with low, medium, and high mean heart rate (HR), or low, medium, and high mean respiration rate (RR). Results showed that ambulatory RMSSD, pvRSA, and HF power are highly correlated and that their correlation is stable across time, ambulatory conditions, and a wide range of resting HR and RR values. RMSSD appears to be the most cost-efficient measure of RSA. PMID- 17343705 TI - Reliability of cardiovascular reactivity to stress: internal consistency. AB - Research on the reliability of cardiovascular reactivity has focused on temporal stability and intertask consistency with only modest results. The present study evaluated the internal consistency reliability of cardiovascular reactivity in three large samples of adolescents and young adults (N=326, 136, and 142). Impedance cardiographic and blood pressure measures were recorded at rest and during standard laboratory stress tasks (math, video game, cold pressor). The reliability of cardiovascular reactivity within tasks, as assessed by Cronbach's alpha coefficient of internal consistency, ranged from alpha=.83 to .96 for 4-min to 5-min math tasks, and alpha=.65 to .94 for 3-min video game and cold pressor tasks. Although highly reliable within tasks, cardiovascular reactivity was less reliable across tasks, even within a single testing session. Possible reasons for the discrepancy between internal consistency and intertask consistency are discussed. PMID- 17343706 TI - Cerebral blood flow in essential hypotension during emotional activation. AB - Variations of blood flow velocity in the left and right middle cerebral arteries (MCA) were measured in 20 hypotensive women and 20 normotensive control subjects during emotional stimulation using functional transcranial Doppler sonography (fTDS). The emotional stimuli were composed of three series (neutral, pleasant, and unpleasant) of 20 pictures from the International Affective Picture System (IAPS). Both groups exhibited greater increases in right than left MCA blood flow during emotional stimulation. However hypotensive subjects showed smaller increases in blood flow than did normotensive controls. Furthermore hypotensives exhibited lower MCA blood flow velocity in both hemispheres at rest than did normotensives. Nevertheless the hypotensive group rated the emotional pictures as more arousing than did the control group. Results suggest a decreased blood flow, in addition to peripheral, in the central nervous system (CNS) of hypotensives, which was associated with normal emotional responses for both valence and hemispherical asymmetry, but also with a general increase of arousal levels. This dissociation might be related to an increase in anterior cerebral arteries (ACA) blood flow and/or to hypotension-mediated baroreceptors' up-regulation to the reticular system. PMID- 17343707 TI - Decomposition of the ERP late posterior negativity: effects of retrieval and response fluency. AB - Negativity elicited by recognized items over posterior sites--the late posterior negativity (LPN)--has been linked to action monitoring, task "uncertainty," and contextual retrieval. Four recognition tests required retrieval of encoding operations. Task fluency was assumed to increase with each block. The responses assigned to the episodic sources were reversed in Block 3 to reduce response fluency. Dissociable LPNs were identified; the 1200-1900-ms LPN was insensitive to task and response fluency and may reflect the maintenance of a retrieved episode. The 600-1200-ms LPN was sensitive to task fluency and may index the search for episodic information. A response-related LPN was sensitive to response fluency and was consistent with an action monitoring role. The findings confirm that the LPN is functionally heterogeneous, and comprises subcomponents sensitive to retrieval fluency, action monitoring, and postretrieval processing respectively. PMID- 17343708 TI - Target-to-target interval, intensity, and P300 from an auditory single-stimulus task. AB - Target-to-target interval (TTI) is a primary determinant of P300 amplitude, such that longer TTIs yield larger components than shorter intervals. Systematic manipulations of TTI affect component amplitude, latency, and associated response time in a fashion that suggests that the template update hypothesis can account for these outcomes. The present study examines whether manipulations of TTI (from 1 to 16 s) and stimulus intensity (soft and loud tones) produce outcomes consistent with this hypothesis. A single-stimulus task was employed in which only target stimuli were presented. P300 amplitude increased, peak latency decreased, and response time increased as TTI became longer, with less effect for soft compared to loud stimulus conditions on P300 amplitude at Pz. TTI increases also augmented N100 amplitude, with consistently smaller amplitudes obtained for soft relative to loud stimuli. Overall, P300 measures are sensitive to both temporal and physical stimulus factors. Theoretical implications are discussed. PMID- 17343709 TI - Surprise, surprise: two distinct components in the visually evoked distractor effect. AB - The distractor effect is an inhibition of saccades shortly after a sudden visual event. It has been explained both as an oculomotor reflex and as a manifestation of the orienting response. To clarify which explanation is more appropriate, we investigated a possible habituation of this effect. Visual and auditory distractors were presented at gaze-contingent intervals during the perception of meaningful pictures. Both reflexlike and modifiable components were present in the visual distractor effect, with latencies of about 110 and 180 ms, respectively. The influence of visual and auditory distractors on saccades preceded the earliest changes in cortical ERPs. Only for long-term habituation in the visual modality was a correlation with ERPs (N1) found. PMID- 17343710 TI - Memory-related ERP components for experimentally learned faces and names: characteristics and parallel-test reliabilities. AB - Previous research with preexperimentally familiar faces and names has identified several memory-related components in the event-related potential (ERP). Here we aimed to characterize these components while controlling the quality of long-term memory with a standardized learning procedure for unfamiliar faces and names. After 1 week, recognition was tested in a repetition priming paradigm. Both early repetition effects (ERE/N250r) and old/new effects had very similar time course and domain-related scalp topographies as has been reported for preexperimentally familiar stimuli. The late repetition effects (LRE/N400) showed domain-specific scalp topographies, possibly reflecting the greater ease of deriving semantic codes from faces. Importantly, parallel-test reliabilities of performance and memory-related ERP components were high, thus demonstrating the utility of face learning for formal assessment procedures in person recognition. PMID- 17343711 TI - Brain electrical correlates of dimensional weighting: an ERP study. AB - In visual search, there is a reaction time (RT) cost for targets on a given trial if the previous target was defined in a different dimension. According to the "dimension-weighting" account (Muller, Heller, & Ziegler, 1995), limited attentional weight needs to be shifted to the new dimension, resulting in slower RTs. The present study aimed at identifying brain electrical correlates associated with the weight shift. Analyses of ERPs revealed several components to reflect dimension changes whether the task was to detect the target or to identify its defining dimension. N2 amplitudes were more negative whenever the dimension changed. The P3 exhibited latency differences that mirrored RTs in both tasks, but the amplitudes showed no direct relation to stimulus- or response related processes. Finally, slow-wave amplitudes were enhanced for dimension changes. Taken together, the results provide support for relatively early, perceptual processes underlying dimension change costs. PMID- 17343712 TI - Music and emotion: electrophysiological correlates of the processing of pleasant and unpleasant music. AB - Human emotion and its electrophysiological correlates are still poorly understood. The present study examined whether the valence of perceived emotions would differentially influence EEG power spectra and heart rate (HR). Pleasant and unpleasant emotions were induced by consonant and dissonant music. Unpleasant (compared to pleasant) music evoked a significant decrease of HR, replicating the pattern of HR responses previously described for the processing of emotional pictures, sounds, and films. In the EEG, pleasant (contrasted to unpleasant) music was associated with an increase of frontal midline (Fm) theta power. This effect is taken to reflect emotional processing in close interaction with attentional functions. These findings show that Fm theta is modulated by emotion more strongly than previously believed. PMID- 17343713 TI - The electrophysiological correlate of contour integration is similar for color and luminance mechanisms. AB - Contour integration perceptually links together similarly oriented line elements hidden between randomly oriented distracters. To investigate how contour integration depends on early sensory processing, we compared the electrophysiological correlate of contour integration of elements defined by luminance (black-and-white) or isoluminant color (red-and-green) contrasts. Detection performance for color- and luminance-defined contours (both open and closed) was matched. Detectable contours elicited a negative shift over posterior electrodes starting 220 ms after stimulus onset. The shift occurred for both color and luminance contrasts, even when possible luminance artifacts in red-and green stimuli were masked. This indicates a common physiological processing stream for orientation-based contour integration of red-and-green and black-and white elements. PMID- 17343714 TI - A psychological refractory period in access to visual short-term memory and the deployment of visual-spatial attention: multitasking processing deficits revealed by event-related potentials. AB - In this psychological refractory period (PRP) experiment, a tone (T1) was presented, followed by a visual target (T2) embedded in a bilateral display, and a speeded response was required for each target. The T1-T2 stimulus onset asynchrony (SOA) was 300, 650, or 1000 ms. Mean response time to T2 increased as SOA was reduced, replicating the well-known PRP effect. Importantly, the N2pc component of the event-related potential was progressively attenuated as SOA was reduced, and the onset latency of the sustained posterior contralateral negativity (SPCN) that follows the N2pc was progressively lengthened. Conditional analysis based on Task1 difficulty corroborated the analyses based on effects of SOA. The results suggest that central processing leading to the PRP effect interferes with the deployment of visual-spatial attention (as indexed by the N2pc) and delays encoding into visual short-term memory (as indexed by the SPCN onset latency). PMID- 17343715 TI - Localization of temporal preparation effects via trisected reaction time. AB - Previous research using nonchronometric measures in humans and animals has shown that warning signals can influence stages of processing throughout the reaction time (RT) interval. However, latency measures indicate that warning effects on RT are not due to the speeding of motor processes, at least not late ones. To better isolate the chronometric effects of temporal preparation, we used lateralized event-related potentials to divide mean RT into three time segments. Foreperiod duration had only a small, nonsignificant influence on the first and last segments (early visual and late motor processes, respectively). The chronometric effect was mainly restricted to the middle interval, which extended from onset of the N2pc component to onset of the lateralized readiness potential. The results imply that temporal preparation primarily speeds late perception, response selection or early motor processes. PMID- 17343716 TI - Impact of stimulus signal-to-noise ratio on prepulse inhibition of acoustic startle. AB - Prepulse inhibition (PPI) of the human acoustic startle response is reduced in the presence of background noise of a sufficient intensity, possibly due to a reduction in signal-to-noise ratio (prepulse intensity relative to background noise). We examined this hypothesis by varying prepulse intensity and background noise intensity in order to hold three different signal-to-noise ratios constant (5, 15, and 25 dB(A) above background noise intensity). The results showed that signal-to-noise ratio proved to be a more important factor than absolute stimulus intensity in determining the degree of PPI of startle eyeblink response magnitude. Therefore, the effectiveness of a prepulse is determined by prepulse salience, not intensity, and this effectiveness is equivalent across a range of physical intensities. PMID- 17343717 TI - Defibrillator therapies in hypertrophic cardiomyopathy: too many swings at bad pitches? PMID- 17343718 TI - Sustained right ventricular tachycardia originating close to defibrillator lead tip in hypertrophic cardiomyopathy. AB - The case of a 57-year-old woman with a longstanding history of obstructive hypertrophic cardiomyopathy in dilatative phase and incessant monomorphic ventricular tachycardia is reported. Endocardial recordings and electroanatomic mapping suggested local reentry involving right ventricular apical septum, close to a pacing/defibrillation lead tip. Radiofrequency pulses delivered at this site resulted in definite cure of the arrhythmia. It is possible that fibrotic reaction around pacing/defibrillation lead in a diseased myocardium substrate has contributed to the creation of a reentry circuit. PMID- 17343719 TI - Serious complications from dislocation of a Watchman left atrial appendage occluder. AB - Left atrial appendage (LAA) elimination is regarded to protect patients with atrial fibrillation (AF) from stroke or embolism. The Watchman occluder is a device for percutaneous LAA occlusion and is at present investigated in the PROTECT AF trial. In a 78-year-old man, embolization of the Watchman device occurred 10 minutes after implantation. At emergency cardiac surgery, the device was removed from the aortic valve and an aortic bioprosthesis and a pacemaker had to be implanted. One year postoperatively, he still suffers from heart failure. This case shows that percutaneous LAA occlusion may result in serious complications. PMID- 17343720 TI - Magnetic navigation in left-sided AV reentrant tachycardias: preliminary results of a retrograde approach. AB - INTRODUCTION: A novel magnetic navigation system allows remote guidance of floppy radiofrequency (RF) ablation catheters. We evaluated the feasibility of mapping and ablation of left-sided accessory pathways (APs) using the retrograde transaortic approach with this system. This might open the gate to retrograde ablation of left atrial arrhythmias. METHODS AND RESULTS: Twenty consecutive patients were included. A Helios II was used in five and in 15 a Celsius RMT RF catheter with higher magnetic mass and different flexibility was used. Mapping and ablation were attempted. The learning curve was analyzed. Ablation was acutely successful in 60% of the patients using the Helios II and in 80% using the Celsius RMT. Median procedure time was 158 minutes, with median patient and physician fluoroscopy times of 26 and 4 minutes. In the last 10 patients, procedure times became significantly shorter (median 122 minutes, only Celsius RMT catheters) and standard catheters had to be used only twice. No complications occurred. CONCLUSIONS: Remote retrograde transaortic RF ablation of left-sided APs is feasible, safe, and reduces the physician's fluoroscopy exposure. There is a very steep initial learning curve, with the success rate increasing from 50% in the first 10 cases to 80% in the last 10 cases. Different catheter configurations may influence the outcome. PMID- 17343721 TI - Laser lead extraction in adult congenital heart disease. AB - BACKGROUND: In adults with congenital heart disease (ACHD), lead extraction procedures are expected to parallel increasing transvenous pacemaker and defibrillator implantations. We sought to assess the safety and feasibility of laser lead extraction in ACHD. METHODS AND RESULTS: All laser lead extractions (Spectranectics, Colorado Springs, CO, USA) performed at the Montreal Heart Institute between September 2000 and August 2005 were prospectively registered. Efficacy and complications in patients with ACHD were compared to the larger cohort. Laser lead extraction was attempted on 270 leads in 175 patients. In ACHD, 23 (five atrial, 15 ventricular pacing, and three defibrillator) leads were targeted in 16 patients. Indications were: infection 44%, dysfunction 25%, upgrade 25%, and pain 6%. Patients with ACHD were younger (43.0 +/- 13.5 vs 63.7 +/- 14.7 years, P < 0.0001) and had a higher proportion of active fixation leads (74% vs 37%, P = 0.0013). Lead age in patients with and without ACHD was 9.0 +/- 5.2 vs 7.7 +/- 5.2 years (P = 0.2713). Overall, 21 of 23 leads (91%) were successfully extracted in ACHD compared with 220 of 247 leads (89%) (P = 0.7405). One major complication (6.3%) occurred in ACHD (tricuspid valve laceration) compared with five major (3.0%) and eight minor (5.0%) complications in patients without ACHD. Presence of ACHD did not modulate procedural success (OR 1.3, 95% CI [0.3, 5.8]) or complications (OR 1.0, 95% CI [0.2, 4.4]). Median procedural time was 27 minutes longer in ACHD (127 vs 100 minutes, P = 0.0595). CONCLUSION: In selected patients with ACHD, laser lead extraction may be performed with a safety and efficacy profile comparable to patients without ACHD. PMID- 17343722 TI - Effects of aging and ouabain on left atrial arrhythmogenicity. AB - OBJECTIVES: Aging increases atrial fibrillation (AF) vulnerability. The left atrium (LA) is important for the generation of AF. However, the effect of aging on the electrophysiological properties of the LA in general, on the specific LA sites, and of possible accentuation of regional differences between the LA sites with aging is not clear. The purpose of this study was to evaluate the effects of aging on the LA electrophysiological heterogeneity and ouabain-induced arrhythmogenicity. METHODS: We used conventional microelectrodes to record the action potentials (APs) in isolated young (age, 3 months) and aged (age, 3 years) rabbit LA posterior wall (LAPW) and LA appendage (LAA) tissue specimens before and after the administration of ouabain. RESULTS: Young LAPWs (n = 10) had larger AP amplitudes than young LAAs (n = 10, P < 0.05), and aged LAPWs (n = 9) had longer AP durations than aged LAAs (n = 9, P < 0.05). Ouabain (1 microM) induced a higher incidence (80% vs 30%, P < 0.05) of delayed afterdepolarizations (DADs) and spontaneous activity (60% vs 10%, P < 0.05) in the young LAPWs than in the young LAAs. Compared with the young group, the aged LAs had a higher incidence of DADs with a less negative resting membrane potential and smaller maximum upstroke velocity. After the ouabain (1 microM) administration, the aged LAPWs had a greater shortening of the AP duration. Ouabain-induced spontaneous activity was similar between the young and aged groups. CONCLUSIONS: Aging enhanced the LA regional electrical heterogeneity and LAPW arrhythmogenesis. PMID- 17343723 TI - Electrophysiologic manifestations of ventricular tachyarrhythmias provoking appropriate defibrillator interventions in high-risk patients with hypertrophic cardiomyopathy. AB - INTRODUCTION: Our objective was to determine features of ventricular tachyarrhythmias triggering appropriate implantable cardioverter-defibrillator (ICD) interventions in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: The study cohort was 68 high-risk HCM patients who received ICDs for primary sudden cardiac death prevention from 1995 to 2003. All episodes of sustained ventricular tachyarrhythmias identified by stored intracardiac electrograms were analyzed. Nine patients had 51 episodes of sustained ventricular tachyarrhythmic events that required device therapy (mean follow-up, 3.4 +/- 2.2 years; cumulative event rate, 3.2% per year): five had 47 episodes of monomorphic ventricular tachycardia (VT); four each had one episode of ventricular fibrillation (VF). Sinus tachycardia or atrial fibrillation was the initiating rhythm in five of nine patients and in 43 of 51 episodes of events. Of the 17 episodes of monomorphic VT detected in the VT zone, 16 (94%) were terminated by antitachycardia pacing. Thirty episodes of monomorphic VT were detected in the VF zone and were terminated by defibrillation. CONCLUSION: Sustained monomorphic VT is common in a high-risk cohort with HCM. Sinus tachycardia is often the initiating rhythm, suggesting that high sympathetic drive may be proarrhythmic when a susceptible substrate is present. Antitachycardia pacing is highly effective in terminating VT in this patient population. PMID- 17343724 TI - Utility of mobile cardiac outpatient telemetry for the diagnosis of palpitations, presyncope, syncope, and the assessment of therapy efficacy. AB - INTRODUCTION: Continuous mobile cardiac outpatient telemetry (MCOT) may have several advantages over traditional ambulatory monitoring systems in the diagnostic evaluation of symptoms such as palpitations, dizziness, and syncope. However, only limited published data are available showing its advantages. METHODS AND RESULTS: We reviewed the records of 122 consecutive patients evaluated using MCOT for palpitations, presyncope/syncope, or to monitor the efficacy of a specific antiarrhythmic therapy. Ten of 17 patients (59%) studied for presyncope/syncope had a diagnosis made with MCOT. Eight of these 17 patients had a previous negative evaluation for presyncope/syncope and five had an event correlated with the heart rhythm during the monitoring period. Nineteen patients monitored for palpitations or presyncope/syncope were asymptomatic during monitoring but had a prespecified arrhythmia detected. When MCOT was used as the first ambulatory monitoring system to evaluate palpitations (n = 18), 73% of patients correlated their symptoms with the underlying cardiac rhythm. Seven of 21 patients monitored for medication titration had dosage adjustments during outpatient monitoring. CONCLUSIONS: MCOT can detect asymptomatic clinically significant arrhythmias, and was especially useful to identify the cause of presyncope/syncope, even in patients with a previous negative workup. This outpatient monitoring system allows patients to undergo daily medication dose titration in the outpatient setting, thus avoiding hospitalization. PMID- 17343725 TI - Does respiratory health contribute to the effects of long-term air pollution exposure on cardiovascular mortality? AB - BACKGROUND: There is growing epidemiological evidence that short-term and long term exposure to high levels of air pollution may increase cardiovascular morbidity and mortality. In addition, epidemiological studies have shown an association between air pollution exposure and respiratory health. To what extent the association between cardiovascular mortality and air pollution is driven by the impact of air pollution on respiratory health is unknown. The aim of this study was to investigate whether respiratory health at baseline contributes to the effects of long-term exposure to high levels of air pollution on cardiovascular mortality in a cohort of elderly women. METHOD: We analyzed data from 4750 women, aged 55 at the baseline investigation in the years 1985-1994. 2593 of these women had their lung function tested by spirometry. Respiratory diseases and symptoms were asked by questionnaire. Ambient air pollution exposure was assessed by the concentrations of NO2 and total suspended particles at fixed monitoring sites and by the distance of residency to a major road. A mortality follow-up of these women was conducted between 2001 and 2003. For the statistical analysis, Cox' regression was used. RESULTS: Women with impaired lung function or pre-existing respiratory diseases had a higher risk of dying from cardiovascular causes. The impact of impaired lung function declined over time. The risk ratio (RR) of women with forced expiratory volume in one second (FEV1) of less than 80% predicted to die from cardiovascular causes was RR = 3.79 (95%CI: 1.64-8.74) at 5 years survival time and RR = 1.35 (95%CI: 0.66-2.77) at 12 years. The association between air pollution levels and cardiovascular death rate was strong and statistically significant. However, this association did only change marginally when including indicators of respiratory health into the regression analysis. Furthermore, no interaction between air pollution and respiratory health on cardiovascular mortality indicating a higher risk of those with impaired respiratory health could be detected. CONCLUSION: Respiratory health is a predictor for cardiovascular mortality. In women followed about 15 years after the baseline investigation at age 55 years long-term air pollution exposure and impaired respiratory health were independently associated with increased cardiovascular mortality. PMID- 17343726 TI - HIV-1 integrase inhibitors are substrates for the multidrug transporter MDR1-P glycoprotein. AB - BACKGROUND: The discovery of diketoacid-containing derivatives as inhibitors of HIV-1 Integrase (IN) (IN inhibitors, IINs) has played a major role in validating this enzyme as an important target for antiretroviral therapy. Since the in vivo efficacy depends on access of these drugs to intracellular sites where HIV-1 replicates, we determined whether the IINs are recognized by the multidrug transporter MDR1-P-glycoprotein (P-gp) thereby reducing their intracellular accumulation. To address the effect of IINs on drug transport, nine quinolonyl diketo acid (DKA) derivatives active on the HIV-1 IN strand transfer (ST) step and with EC50 ranging from 1.83 to >50 mum in cell-based assays were tested for their in vitro interaction with P-gp in the CEM-MDR cell system. IINs were investigated for the inhibition and induction of the P-gp function and expression as well as for multidrug resistance (MDR) reversing ability. RESULTS: The HIV-1 IINs act as genuine P-gp substrates by inhibiting doxorubicin efflux and inducing P-gp functional conformation changes as evaluated by the modulation of UIC2 mAb epitope. Further, IINs chemosensitize MDR cells to vinblastine and induce P-gp expression in drug sensitive revertants of CEM-MDR cells. CONCLUSION: To our knowledge, this is the first demonstration that HIV-1 IINs are P-gp substrates. This biological property may influence the absorption, distribution and elimination of these novels anti HIV-1 compounds. PMID- 17343727 TI - Automated array-CGH optimized for archival formalin-fixed, paraffin-embedded tumor material. AB - BACKGROUND: Array Comparative Genomic Hybridization (aCGH) is a rapidly evolving technology that still lacks complete standardization. Yet, it is of great importance to obtain robust and reproducible data to enable meaningful multiple hybridization comparisons. Special difficulties arise when aCGH is performed on archival formalin-fixed, paraffin-embedded (FFPE) tissue due to its variable DNA quality. Recently, we have developed an effective DNA quality test that predicts suitability of archival samples for BAC aCGH. METHODS: In this report, we first used DNA from a cancer cell-line (SKBR3) to optimize the aCGH protocol for automated hybridization, and subsequently optimized and validated the procedure for FFPE breast cancer samples. We aimed for highest throughput, accuracy, and reproducibility applicable to FFPE samples, which can also be important in future diagnostic use. RESULTS: Our protocol of automated array-CGH on archival FFPE ULS labeled DNA showed very similar results compared with published data and our previous manual hybridization method. CONCLUSION: This report combines automated aCGH on unamplified archival FFPE DNA using non-enzymatic ULS labeling, and describes an optimized protocol for this combination resulting in improved quality and reproducibility. PMID- 17343728 TI - Habitat suitability mapping of Anopheles darlingi in the surroundings of the Manso hydropower plant reservoir, Mato Grosso, Central Brazil. AB - BACKGROUND: Hydropower plants provide more than 78 % of Brazil's electricity generation, but the country's reservoirs are potential new habitats for main vectors of malaria. In a case study in the surroundings of the Manso hydropower plant in Mato Grosso state, Central Brazil, habitat suitability of Anopheles darlingi was studied. Habitat profile was characterized by collecting environmental data. Remote sensing and GIS techniques were applied to extract additional spatial layers of land use, distance maps, and relief characteristics for spatial model building. RESULTS: Logistic regression analysis and ROC curves indicate significant relationships between the environment and presence of An. darlingi. Probabilities of presence strongly vary as a function of land cover and distance from the lake shoreline. Vector presence was associated with spatial proximity to reservoir and semi-deciduous forests followed by Cerrado woodland. Vector absence was associated with open vegetation formations such as grasslands and agricultural areas. We suppose that non-significant differences of vector incidences between rainy and dry seasons are associated with the availability of anthropogenic breeding habitat of the reservoir throughout the year. CONCLUSION: Satellite image classification and multitemporal shoreline simulations through DEM-based GIS-analyses consist in a valuable tool for spatial modeling of A. darlingi habitats in the studied hydropower reservoir area. Vector presence is significantly increased in forested areas near reservoirs in bays protected from wind and wave action. Construction of new reservoirs under the tropical, sub humid climatic conditions should therefore be accompanied by entomologic studies to predict the risk of malaria epidemics. PMID- 17343729 TI - Trends in the HIV related hospital admissions in the HAART era in Barbados, 2004 2006. AB - BACKGROUND: To investigate the reasons for hospitalizations and its outcome in the era of HAART in Barbados. This report also describes the profile of the HIV infected persons who are hospitalized in the HAART era. METHODS: This is a retrospective study of HIV related admissions in this country. We examined the admission case notes of all the adult admissions to the Queen Elizabeth Hospital where one of the discharge diagnosis was HIV infection during the April 2004 through March 2006. Data collected included patients' profile, including the date of diagnosis of HIV infection, outcome of the current admission in term of discharge or death and the final diagnosis at the time of discharge or death. RESULTS: Over the 24 months period there were 431 adult admissions to the medical wards of the Queen Elizabeth Hospital where one of the discharge diagnosis was HIV infection and this accounted for 5.9% of all medical admissions. 258(60%) admissions were in persons who were known to be HIV infected prior to the current admission, where as diagnosis of HIV infection was made for the first time during the current admission in case of remaining 76(47.5%) cases. Nearly half of those hospitalized, had a CD 4 cell counts of < 200/microL. Over all, opportunistic infection was the commonest (35%) discharge diagnosis, followed by serious bacterial infections, anemia and HIV nephropathy. The outcome of these admissions was death in 30 (14.2%) cases where as patient was discharged out in the remaining 181 (85.8%) cases. Of the medical admissions with HIV as one of the discharge diagnosis during the period April 04 through March 05, 43% were newly diagnosed HIV infection and the corresponding figure for the period April 05 through March 06 was 35% (P = 0.54). During the April 05 through March 04 significantly higher proportion of HIV infected adults had Anemia with a Hemoglobin less than 10 g/dL (P = 0.044), HIV related nephropathy (P = 0.0003), HAART toxicity (P = < 0.0001) and a Non-AIDS related conditions (P = 0.043) as one of the final discharge diagnosis. CONCLUSION: A significant proportion of patients admitted with HIV infection were the newly diagnosed and severely immuno suppressed. An opportunistic infection continues to be the commonest discharge diagnosis, although there was a growing trend in the proportion of the discharge diagnosis being HAART toxicity and Non-AIDS related conditions. Over all hospitalization of HIV infected persons still carries a significant risk of mortality. PMID- 17343730 TI - Structure and characterization of a novel chicken biotin-binding protein A (BBP A). AB - BACKGROUND: The chicken genome contains a BBP-A gene showing similar characteristics to avidin family genes. In a previous study we reported that the BBP-A gene may encode a biotin-binding protein due to the high sequence similarity with chicken avidin, especially at regions encoding residues known to be located at the ligand-binding site of avidin. RESULTS: Here, we expand the repertoire of known macromolecular biotin binders by reporting a novel biotin binding protein A (BBP-A) from chicken. The BBP-A recombinant protein was expressed using two different expression systems and purified with affinity chromatography, biochemically characterized and two X-ray structures were solved in complex with D-biotin (BTN) and in complex with D-biotin D-sulfoxide (BSO). The BBP-A protein binds free biotin with high, "streptavidin-like" affinity (Kd ~ 10-13 M), which is about 50 times lower than that of chicken avidin. Surprisingly, the affinity of BBP-A for BSO is even higher than the affinity for BTN. Furthermore, the solved structures of the BBP-A--BTN and BBP-A--BSO complexes, which share the fold with the members of the avidin and lipocalin protein families, are extremely similar to each other. CONCLUSION: BBP-A is an avidin-like protein having a beta-barrel fold and high affinity towards BTN. However, BBP-A differs from the other known members of the avidin protein family in thermal stability and immunological properties. BBP-A also has a unique ligand binding property, the ability to bind BTN and BSO at comparable affinities. BBP-A may have use as a novel material in, e.g. modern bio(nano)technological applications. PMID- 17343732 TI - Is abdominal wall contraction important for normal voiding in the female rat? AB - BACKGROUND: Normal voiding behavior in urethane-anesthetized rats includes contraction of the abdominal wall striated muscle, similar to the visceromotor response (VMR) to noxious bladder distension. Normal rat voiding requires pulsatile release of urine from a pressurized bladder. The abdominal wall contraction accompanying urine flow may provide a necessary pressure increment for normal efficient pulsatile voiding. This study aimed to evaluate the occurrence and necessity of the voiding-associated abdominal wall activity in urethane-anesthetized female rats METHODS: A free-voiding model was designed to allow assessment of abdominal wall activity during voiding resulting from physiologic bladder filling, in the absence of bladder or urethral instrumentation. Physiologic diuresis was promoted by rapid intravascular hydration. Intercontraction interval (ICI), voided volumes and EMG activity of the rectus abdominis were quantified. The contribution of abdominal wall contraction to voiding was eliminated in a second group of rats by injecting botulinum-A (BTX, 5 U) into each rectus abdominis to induce local paralysis. Uroflow parameters were compared between intact free-voiding and BTX-prepared animals. RESULTS: Abdominal wall response is present in free voiding. BTX preparation eliminated the voiding-associated EMG activity. Average per-void volume decreased from 1.8 ml to 1.1 ml (p < 0.05), and reduced average flow from 0.17 ml/sec to 0.11 ml/sec (p < 0.05). Intercontraction interval (ICI) was not changed by BTX pretreatment. CONCLUSION: The voiding-associated abdominal wall response is a necessary component of normal voiding in urethane anesthetized female rats. As the proximal urethra may be the origin of the afferent signaling which results in the abdominal wall response, the importance of the bladder pressure increment due to this response may be in maintaining a normal duration intermittent pulsatile high frequency oscillatory (IPHFO)/flow phase and thus efficient voiding. We propose the term Voiding-associated Abdominal Response (VAR) for the physiologic voiding-associated EMG/abdominal wall response, to distinguish it from the visceromotor response (VMR) to noxious bladder distension. PMID- 17343731 TI - The association between patellar alignment on magnetic resonance imaging and radiographic manifestations of knee osteoarthritis. AB - The aim of our study was to evaluate the association between patellar alignment by using magnetic resonance imaging images and radiographic manifestations of patello-femoral osteoarthritis (OA). Subjects were recruited to participate in a natural history study of symptomatic knee OA. We examined the relation of patellar alignment in the sagittal plane (patellar length ratio (PLR)) and the transverse plane (sulcus angle (SA), lateral patellar tilt angle (LPTA), and bisect offset (BO)) to radiographic features of patello-femoral OA, namely joint space narrowing and patellar osteophytes, using a proportional odds logistic regression model while adjusting for age, sex, and bone mass index (BMI). The study sample consisted of 126 males (average age 68.0 years, BMI 31.2) and 87 females (average age 64.7 years, BMI 31.6), 75% of whom had tibiofemoral OA (a Kellgren-Lawrence score of 2 or more). PLR showed a statistically significant association with joint space narrowing and osteophytosis in the lateral compartment. SA showed significant association with medial joint space narrowing and with lateral and medial patellar osteophytosis. LPTA and BO showed significant association with both radiographic indices of the lateral compartment. Clear linear trends were found in association between PLR, LPTA and BO, and with outcomes associated with lateral patello-femoral OA. SA, LPTA, and BO showed linear trends of association with medial joint space narrowing. Results of our study clearly suggest the association between indices of patellar alignment and such features of patello-femoral OA as osteophytosis and joint space narrowing. Additional studies will be required to establish the normal and abnormal ranges of patellar alignment indices and their longitudinal relation to patello-femoral OA. PMID- 17343733 TI - Modelling the spatial distribution of five natural hazards in the context of the WHO/EMRO Atlas of Disaster Risk as a step towards the reduction of the health impact related to disasters. AB - BACKGROUND: Reducing the potential for large scale loss of life, large numbers of casualties, and widespread displacement of populations that can result from natural disasters is a difficult challenge for the individuals, communities and governments that need to respond to such events. While it is extremely difficult, if not impossible, to predict the occurrence of most natural hazards; it is possible to take action before emergency events happen to plan for their occurrence when possible and to mitigate their potential effects. In this context, an Atlas of Disaster Risk is under development for the 21 Member States that constitute the World Health Organization's (WHO) Eastern Mediterranean (EM) Region and the West Bank and Gaza Strip territory. METHODS AND RESULTS: This paper describes the Geographic Information System (GIS) based methods that have been used in order to create the first volume of the Atlas which looks at the spatial distribution of 5 natural hazards (flood, landslide, wind speed, heat and seismic hazard). It also presents the results obtained through the application of these methods on a set of countries part of the EM Region before illustrating how this type of information can be aggregated for decision making. DISCUSSION AND CONCLUSION: The methods presented in this paper aim at providing a new set of tools for GIS practitioners to refine their analytical capabilities when examining natural hazards, and at the same time allowing users to create more specific and meaningful local analyses. The maps resulting from the application of these methods provides decision makers with information to strengthen their disaster management capacity. It also represents the basis for the reflection that needs to take place regarding populations' vulnerability towards natural hazards from a health perspective. PMID- 17343734 TI - Does the DNA barcoding gap exist? - a case study in blue butterflies (Lepidoptera: Lycaenidae). AB - BACKGROUND: DNA barcoding, i.e. the use of a 648 bp section of the mitochondrial gene cytochrome c oxidase I, has recently been promoted as useful for the rapid identification and discovery of species. Its success is dependent either on the strength of the claim that interspecific variation exceeds intraspecific variation by one order of magnitude, thus establishing a "barcoding gap", or on the reciprocal monophyly of species. RESULTS: We present an analysis of intra- and interspecific variation in the butterfly family Lycaenidae which includes a well-sampled clade (genus Agrodiaetus) with a peculiar characteristic: most of its members are karyologically differentiated from each other which facilitates the recognition of species as reproductively isolated units even in allopatric populations. The analysis shows that there is an 18% overlap in the range of intra- and interspecific COI sequence divergence due to low interspecific divergence between many closely related species. In a Neighbour-Joining tree profile approach which does not depend on a barcoding gap, but on comprehensive sampling of taxa and the reciprocal monophyly of species, at least 16% of specimens with conspecific sequences in the profile were misidentified. This is due to paraphyly or polyphyly of conspecific DNA sequences probably caused by incomplete lineage sorting. CONCLUSION: Our results indicate that the "barcoding gap" is an artifact of insufficient sampling across taxa. Although DNA barcodes can help to identify and distinguish species, we advocate using them in combination with other data, since otherwise there would be a high probability that sequences are misidentified. Although high differences in DNA sequences can help to identify cryptic species, a high percentage of well-differentiated species has similar or even identical COI sequences and would be overlooked in an isolated DNA barcoding approach. PMID- 17343735 TI - Unofficial policy: access to housing, housing information and social services among homeless drug users in Hartford, Connecticut. AB - BACKGROUND: Much research has shown that the homeless have higher rates of substance abuse problems than housed populations and that substance abuse increases individuals' vulnerability to homelessness. However, the effects of housing policies on drug users' access to housing have been understudied to date. This paper will look at the "unofficial" housing policies that affect drug users' access to housing. METHODS: Qualitative interviews were conducted with 65 active users of heroin and cocaine at baseline, 3 and 6 months. Participants were purposively sampled to reflect a variety of housing statuses including homeless on the streets, in shelters, "doubled-up" with family or friends, or permanently housed in subsidized, unsubsidized or supportive housing. Key informant interviews and two focus group interviews were conducted with 15 housing caseworkers. Data were analyzed to explore the processes by which drug users receive information about different housing subsidies and welfare benefits, and their experiences in applying for these. RESULTS: A number of unofficial policy mechanisms limit drug users' access to housing, information and services, including limited outreach to non-shelter using homeless regarding housing programs, service provider priorities, and service provider discretion in processing applications and providing services. CONCLUSION: Unofficial policy, i.e. the mechanisms used by caseworkers to ration scarce housing resources, is as important as official housing policies in limiting drug users' access to housing. Drug users' descriptions of their experiences working with caseworkers to obtain permanent, affordable housing, provide insights as to how access to supportive and subsidized housing can be improved for this population. PMID- 17343736 TI - Sp1/Sp3 and DNA-methylation contribute to basal transcriptional activation of human podoplanin in MG63 versus Saos-2 osteoblastic cells. AB - BACKGROUND: Podoplanin is a membrane mucin that, among a series of tissues, is expressed on late osteoblasts and osteocytes. Since recent findings have focussed on podoplanin's potential role as a tumour progression factor, we aimed at identifying regulatory elements conferring PDPN promoter activity. Here, we characterized the molecular mechanism controlling basal PDPN transcription in human osteoblast-like MG63 versus Saos-2 cells. RESULTS: We cloned and sequenced 2056 nucleotides from the 5'-flanking region of the PDPN gene and a computational search revealed that the TATA and CAAT box-lacking promoter possesses features of a growth-related gene, such as a GC-rich 5' region and the presence of multiple putative Sp1, AP-4 and NF-1 sites. Reporter gene assays demonstrated a functional promoter in MG63 cells exhibiting 30-fold more activity than in Saos-2 cells. In vitro DNase I footprinting revealed eight protected regions flanked by DNaseI hypersensitive sites within the region bp -728 to -39 present in MG63, but not in Saos-2 cells. Among these regions, mutation and supershift electrophoretic mobility shift assays (EMSA) identified four Sp1/Sp3 binding sites and two binding sites for yet unknown transcription factors. Deletion studies demonstrated the functional importance of two Sp1/Sp3 sites for PDPN promoter activity. Overexpression of Sp1 and Sp3 independently increased the stimulatory effect of the promoter and podoplanin mRNA levels in MG63 and Saos-2 cells. In SL2 cells, Sp3 functioned as a repressor, while Sp1 and Sp3 acted positively synergistic. Weak PDPN promoter activity of Saos-2 cells correlated with low Sp1/Sp3 nuclear levels, which was confirmed by Sp1/Sp3 chromatin immunoprecipitations in vivo. Moreover, methylation-sensitive Southern blot analyses and bisulfite sequencing detected strong methylation of CpG sites upstream of bp -464 in MG63 cells, but hypomethylation of these sites in Saos-2 cells. Concomitantly, treatment with the DNA methyltransferase inhibitor 5-azaCdR in combination with trichostatin A (TSA) downregulated podoplanin mRNA levels in MG63 cells, and region-specific in vitro methylation of the distal promoter suggested that DNA methylation rather enhanced than hindered PDPN transcription in both cell types. CONCLUSION: These data establish that in human osteoblast like MG63 cells, Sp1 and Sp3 stimulate basal PDPN transcription in a concerted, yet independent manner, whereas Saos-2 cells lack sufficient nuclear Sp protein amounts for transcriptional activation. Moreover, a highly methylated chromatin conformation of the distal promoter region confers cell-type specific podoplanin upregulation versus Saos-2 cells. PMID- 17343737 TI - Calcium sulfate and platelet-rich plasma make a novel osteoinductive biomaterial for bone regeneration. AB - BACKGROUND: With the present study we introduce a novel and simple biomaterial able to induce regeneration of bone. We theorized that nourishing a bone defect with calcium and with a large amount of activated platelets may initiate a series of biological processes that culminate in bone regeneration. Thus, we engineered CS-Platelet, a biomaterial based on the combination of Calcium Sulfate and Platelet-Rich Plasma in which Calcium Sulfate also acts as an activator of the platelets, therefore avoiding the need to activate the platelets with an agonist. METHODS: First, we tested CS-Platelet in heterotopic (muscle) and orthotopic (bone) bone regeneration bioassays. We then utilized CS-Platelet in a variety of dental and craniofacial clinical cases, where regeneration of bone was needed. RESULTS: The heterotopic bioassay showed formation of bone within the muscular tissue at the site of the implantation of CS-Platelet. Results of a quantitative orthotopic bioassay based on the rat calvaria critical size defect showed that only CS-Platelet and recombinant human BMP2 were able to induce a significant regeneration of bone. A non-human primate orthotopic bioassay also showed that CS Platelet is completely resorbable. In all human clinical cases where CS-Platelet was used, a complete bone repair was achieved. CONCLUSION: This study showed that CS-Platelet is a novel biomaterial able to induce formation of bone in heterotopic and orthotopic sites, in orthotopic critical size bone defects, and in various clinical situations. The discovery of CS-Platelet may represent a cost effective breakthrough in bone regenerative therapy and an alternative or an adjuvant to the current treatments. PMID- 17343738 TI - Home-based exercise rehabilitation in addition to specialist heart failure nurse care: design, rationale and recruitment to the Birmingham Rehabilitation Uptake Maximisation study for patients with congestive heart failure (BRUM-CHF): a randomised controlled trial. AB - BACKGROUND: Exercise has been shown to be beneficial for selected patients with heart failure, but questions remain over its effectiveness, cost-effectiveness and uptake in a real world setting. This paper describes the design, rationale and recruitment for a randomised controlled trial that will explore the effectiveness and uptake of a predominantly home-based exercise rehabilitation programme, as well as its cost-effectiveness and patient acceptability. METHODS/DESIGN: Randomised controlled trial comparing specialist heart failure nurse care plus a nurse-led predominantly home-based exercise intervention against specialist heart failure nurse care alone in a multiethnic city population, served by two NHS Trusts and one primary care setting, in the United Kingdom.169 English speaking patients with stable heart failure, defined as systolic impairment (ejection fraction < or = 40%). with one or more hospital admissions with clinical heart failure or New York Heart Association (NYHA) II/III within previous 24-months were recruited.Main outcome measures at 1 year: Minnesota Living with Heart Failure Questionnaire, incremental shuttle walk test, death or admission with heart failure or myocardial infarction, health care utilisation and costs. Interviews with purposive samples of patients to gain qualitative information about acceptability and adherence to exercise, views about their treatment, self-management of their heart failure and reasons why some patients declined to participate. The records of 1639 patients managed by specialist heart failure services were screened, of which 997 (61%) were ineligible, due to ejection fraction>40%, current NYHA IV, no admission or NYHA II or more within the previous 2 years, or serious co-morbidities preventing physical activity. 642 patients were contacted: 289 (45%) declined to participate, 183 (39%) had an exclusion criterion and 169 (26%) agreed to randomisation. DISCUSSION: Due to safety considerations for home-exercise less than half of patients treated by specialist heart failure services were eligible for the study. Many patients had co-morbidities preventing exercise and others had concerns about undertaking an exercise programme. PMID- 17343739 TI - Theoretical framework and methodological development of common subjective health outcome measures in osteoarthritis: a critical review. AB - Subjective measures involving clinician ratings or patient self-assessments have become recognised as an important tool for the assessment of health outcome. The value of a health outcome measure is usually assessed by a psychometric evaluation of its reliability, validity and responsiveness. However, psychometric testing involves an accumulation of evidence and has recognised limitations. It has been suggested that an evaluation of how well a measure has been developed would be a useful additional criteria in assessing the value of a measure. This paper explored the theoretical background and methodological development of subjective health status measures commonly used in osteoarthritis research. Fourteen subjective health outcome measures commonly used in osteoarthritis research were examined. Each measure was explored on the basis of their i) theoretical framework (was there a definition of what was being assessed and was it part of a theoretical model?) and ii) methodological development (what was the scaling strategy, how were the items generated and reduced, what was the response format and what was the scoring method?). Only the AIMS, SF-36 and WHOQOL defined what they were assessing (i.e. the construct of interest) and no measure assessed was part of a theoretical model. None of the clinician report measures appeared to have implemented a scaling procedure or described the rationale for the items selected or scoring system. Of the patient self-report measures, the AIMS, MPQ, OXFORD, SF-36, WHOQOL and WOMAC appeared to follow a standard psychometric scaling method. The DRP and EuroQol used alternative scaling methods. The review highlighted the general lack of theoretical framework for both clinician report and patient self-report measures. This review also drew attention to the wide variation in the methodological development of commonly used measures in OA. While, in general the patient self-report measures had good methodological development, the clinician report measures appeared less well developed. It would be of value if new measures defined the construct of interest and, that the construct, be part of theoretical model. By ensuring measures are both theoretically and empirically valid then improvements in subjective health outcome measures should be possible. PMID- 17343740 TI - Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells. AB - BACKGROUND: The expression level of osteopontin correlates with the metastatic potential of several tumors. Osteopontin is a well-characterized ligand for the alphavbeta3 integrin. The present study was undertaken to elucidate the possible role of osteopontin/alphavbeta3 signaling in prostate cancer cell migration. RESULTS: We generated stable prostate cancer cell (PC3) lines that over-express osteopontin (PC3/OPN), mutant OPN in the integrin binding-site (PC3/RGDDeltaRGA), and null for OPN (PC3/SiRNA). The following observations were made in PC3/OPN cells as compared with PC3 cells: 1) an increase in multinucleated giant cells and RANKL expression; 2) an increase in CD44 surface expression, interaction of CD44/MMP-9 on the cell surface, MMP-9 activity in the conditioned medium, and cell migration; 3) western blot analysis of concentrated conditioned medium exhibited equal levels of MMP-9 protein in all PC3 cells. However, zymography analysis demonstrated that the levels of MMP-9 activity in the conditioned media reflect the CD44 surface expression pattern of the PC3 cell lines; 4) although MMP-9 and MMP-2 are secreted by PC3 cells, only the secretion of MMP-9 is regulated by OPN expression. A strong down regulation of the above-mentioned processes was observed in PC3/OPN (RGA) and PC3/SiRNA cells. PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. CONCLUSION: Rho signaling plays a crucial role in CD44 surface expression. BPs inhibits the mevalonate pathway, which in turn, prevents the prenylation of a number of small GTPases. Attenuation of Rho GTPase activation by BPs may have contributed to the down regulation of cell surface CD44/MMP-9 interaction, MMP-9 activation/secretion, and cell migration. Taken together, these observations suggest that CD44 surface expression is an important event in the activation of MMP-9 and migration of prostate cancer cells. The various steps involved in the above mentioned signaling pathway and/or the molecules regulating the activation of MMP-9 are potential therapeutic target. PMID- 17343741 TI - Studies of a co-chaperone of the androgen receptor, FKBP52, as candidate for hypospadias. AB - BACKGROUND: Hypospadias is a common inborn error of the male urethral development, for which the aetiology is still elusive. Polymorphic variants in genes involved in the masculinisation of male genitalia, such as the androgen receptor, have been associated with some cases of hypospadias. Co-regulators of the androgen receptor start being acknowledged as possible candidates for hormone resistance instances, which could account for hypospadias. One such molecule, the protein FKBP52, coded by the FKBP4 gene, has an important physiological role in up-regulating androgen receptor activity, an essential step in the development of the male external genitalia. The presence of hypospadias in mice lacking fkbp52 encouraged us to study the sequence and the expression of FKBP4 in boys with isolated hypospadias. PATIENTS AND METHODS: The expression of FKBP52 in the genital skin of boys with hypospadias and in healthy controls was tested by immunohistochemistry. Mutation screening in the FKBF4 gene was performed in ninety-one boys with non syndromic hypospadias. Additionally, two polymorphisms were typed in a larger cohort. RESULTS: Immunohistochemistry shows epithelial expression of FKBP52 in the epidermis of the penile skin. No apparent difference in the FKBP52 expression was detected in healthy controls, mild or severe hypospadias patients. No sequence variants in the FKBP4 gene have implicated in hypospadias in our study. CONCLUSION: FKBP52 is likely to play a role in growth and development of the male genitalia, since it is expressed in the genital skin of prepubertal boys; however alterations in the sequence and in the expression of the FKBP4 gene are not a common cause of non-syndromic hypospadias. PMID- 17343742 TI - Hedgehog pathway activity in the LADY prostate tumor model. AB - BACKGROUND: Robust Hedgehog (Hh) signaling has been implicated as a common feature of human prostate cancer and an important stimulus of tumor growth. The role of Hh signaling has been studied in several xenograft tumor models, however, the role of Hh in tumor development in a transgenic prostate cancer model has never been examined. RESULTS: We analyzed expression of Hh pathway components and conserved Hh target genes along with progenitor cell markers and selected markers of epithelial differentiation during tumor development in the LADY transgenic mouse model. Tumor development was associated with a selective increase in Ihh expression. In contrast Shh expression was decreased. Expression of the Hh target Patched (Ptc) was significantly decreased while Gli1 expression was not significantly altered. A survey of other relevant genes revealed significant increases in expression of Notch-1 and Nestin together with decreased expression of HNF3a/FoxA1, NPDC-1 and probasin. CONCLUSION: Our study shows no evidence for a generalized increase in Hh signaling during tumor development in the LADY mouse. It does reveal a selective increase in Ihh expression that is associated with increased expression of progenitor cell markers and decreased expression of terminal differentiation markers. These data suggest that Ihh expression may be a feature of a progenitor cell population that is involved in tumor development. PMID- 17343743 TI - The role of gamma delta T cells in airway epithelial injury and bronchial responsiveness after chlorine gas exposure in mice. AB - BACKGROUND: Acute exposure to chlorine (Cl2) gas causes epithelial injury and airway dysfunction. gammadelta T cells are present in the mucosal surface of the airways and may contribute to the injury/repair response of the epithelium. METHODS: C57Bl/6J (wild type) and TCR-delta-/- mice exposed to Cl2 (400 ppm) for 5 minutes underwent measurements of airway responses to i.v. methacholine (MCh) at 1, 3, and 5 days after exposure. Bronchoalveolar lavage was performed to determine epithelial and leukocyte counts, and protein content. Tissue repair was assessed by proliferating cell nuclear antigen (PCNA) immunoreactivity and by expression of keratinocyte growth factor (KGF) mRNA by real-time PCR. RESULTS: Wild type mice developed a greater degree of airway hyperresponsiveness to MCh at 1 day post exposure to Cl2 compared with TCR-delta-/- mice. Epithelial cell counts in BAL after Cl2 exposure were greater in TCR-delta-/- mice, but macrophages showed a later peak and granulocyte numbers were lower in TCR-delta-/ than in wild type mice. Both groups had increased levels of total protein content in BAL after Cl2 exposure that resolved after 3 and 5 days, respectively. Epithelial proliferating cell nuclear antigen staining was increased at 1 and 3 days post exposure and was similar in the two groups. KGF mRNA was constitutively expressed in both groups and did not increase significantly after Cl2 but expression was lower in TCR-delta-/- mice. CONCLUSION: The severity of airway epithelial injury after Cl2 is greater in TCR-delta-/- mice but the inflammatory response and the change in airway responsiveness to methacholine are reduced. The rates of epithelial regeneration are comparable in both groups. PMID- 17343744 TI - Different rates of (non-)synonymous mutations in astrovirus genes; correlation with gene function. AB - BACKGROUND: Complete genome sequences of the Astroviridae include human, non human mammalian and avian species. A consensus topology of astroviruses has been derived from nucleotide substitutions in the full-length genomes and from non synonymous nucleotide substitutions in each of the three ORFs. Analyses of synonymous substitutions displayed a loss of tree structure, suggesting either saturation of the substitution model or a deviant pattern of synonymous substitutions in certain virus species. RESULTS: We analyzed the complete Astroviridae family for the inference of adaptive molecular evolution at sites and in branches. High rates of synonymous mutations are observed among the non human virus species. Deviant patterns of synonymous substitutions are found in the capsid structural genes. Purifying selection is a dominant force among all astrovirus genes and only few codon sites showed values for the dN/dS ratio that may indicate site-specific molecular adaptation during virus evolution. One of these sites is the glycine residue of a RGD motif in ORF2 of human astrovirus serotype 1. RGD or similar integrin recognition motifs are present in nearly all astrovirus species. CONCLUSION: Phylogenetic analysis directed by maximum likelihood approximation allows the inclusion of significantly more evolutionary history and thereby, improves the estimation of dN and dS. Sites with enhanced values for dN/dS are prominent at domains in charge of environmental communication (f.i. VP27 and domain 4 in ORF1a) more than at domains dedicated to intrinsic virus functions (f.i. VP34 and ORF1b (the virus polymerase)). Integrin recognition may play a key role in astrovirus to target cell attachment. PMID- 17343745 TI - Bayesian meta-analysis models for microarray data: a comparative study. AB - BACKGROUND: With the growing abundance of microarray data, statistical methods are increasingly needed to integrate results across studies. Two common approaches for meta-analysis of microarrays include either combining gene expression measures across studies or combining summaries such as p-values, probabilities or ranks. Here, we compare two Bayesian meta-analysis models that are analogous to these methods. RESULTS: Two Bayesian meta-analysis models for microarray data have recently been introduced. The first model combines standardized gene expression measures across studies into an overall mean, accounting for inter-study variability, while the second combines probabilities of differential expression without combining expression values. Both models produce the gene-specific posterior probability of differential expression, which is the basis for inference. Since the standardized expression integration model includes inter-study variability, it may improve accuracy of results versus the probability integration model. However, due to the small number of studies typical in microarray meta-analyses, the variability between studies is challenging to estimate. The probability integration model eliminates the need to model variability between studies, and thus its implementation is more straightforward. We found in simulations of two and five studies that combining probabilities outperformed combining standardized gene expression measures for three comparison values: the percent of true discovered genes in meta-analysis versus individual studies; the percent of true genes omitted in meta-analysis versus separate studies, and the number of true discovered genes for fixed levels of Bayesian false discovery. We identified similar results when pooling two independent studies of Bacillus subtilis. We assumed that each study was produced from the same microarray platform with only two conditions: a treatment and control, and that the data sets were pre-scaled. CONCLUSION: The Bayesian meta analysis model that combines probabilities across studies does not aggregate gene expression measures, thus an inter-study variability parameter is not included in the model. This results in a simpler modeling approach than aggregating expression measures, which accounts for variability across studies. The probability integration model identified more true discovered genes and fewer true omitted genes than combining expression measures, for our data sets. PMID- 17343747 TI - Nasal septal perforation 1981-2005: changes in etiology, gender and size. AB - BACKGROUND: Septal perforation is an uncommon but very bothersome illness and treatment is difficult particularly with large perforations. We wanted to establish the etiology and size of nasal septal perforations in an attempt to implement preventive measures. METHODS: This is an open, prospective clinical study of patients seen at our hospital from 1981 to 2005. The clinical data of size, gender and etiology have been recorded consecutively. RESULTS: One hundred and ninety seven patients (100 male, 97 female) were evaluated. Between 1981 and 1995 nasal septal perforation was caused by surgery in 40 of 102 (39.2 %). In the period 1995 to and inclusive of 2005 this percentage decreased as septal resection has been replaced by septo/septorhinoplasty. The latter was the cause for septal perforation in 14.7% in the last period. Nasal steroid and decongestive sprays have emerged as an important cause (28.4 %) during the last ten years particularly in females. In the first period 44 (43.1 %) and in the last 53 (55.7 %) patients were females. There was a noticeable reduction in the number of septal perforations 15 mm or larger in the last period. CONCLUSION: Nasal steroid and decongestive sprays are now important causes for septal perforation. Information about this complication should be given with an advice to immediately report increasing and bothersome crusting and bleeding. Warning of the simultaneous use of nasal steroid and decongestive sprays should be addressed particularly to females. All patients with symptoms of septal perforation should promptly be referred to otolaryngologists for treatment. PMID- 17343748 TI - Alternative ion channel splicing in mesial temporal lobe epilepsy and Alzheimer's disease. AB - BACKGROUND: Alternative gene transcript splicing permits a single gene to produce multiple proteins with varied functions. Bioinformatic investigations have identified numerous splice variants, but whether these transcripts are translated to functional proteins and the physiological significance of these alternative proteins are largely unknown. Through direct identification of splice variants associated with disease states, we can begin to address these questions and to elucidate their roles in disease predisposition and pathophysiology. This work specifically sought to identify disease-associated alternative splicing patterns in ion channel genes by comprehensively screening affected brain tissue collected from patients with mesial temporal lobe epilepsy and Alzheimer's disease. New technology permitting the screening of alternative splice variants in microarray format was employed. Real time quantitative PCR was used to verify observed splice variant patterns. RESULTS: This work shows for the first time that two common neurological conditions are associated with extensive changes in gene splicing, with 25% and 12% of the genes considered having significant changes in splicing patterns associated with mesial temporal lobe epilepsy and Alzheimer's disease, respectively. Furthermore, these changes were found to exhibit unique and consistent patterns within the disease groups. CONCLUSION: This work has identified a set of disease-associated, alternatively spliced gene products that represent high priorities for detailed functional investigations into how these changes impact the pathophysiology of mesial temporal lobe epilepsy and Alzheimer's disease. PMID- 17343749 TI - Pair of lice lost or parasites regained: the evolutionary history of anthropoid primate lice. AB - BACKGROUND: The parasitic sucking lice of primates are known to have undergone at least 25 million years of coevolution with their hosts. For example, chimpanzee lice and human head/body lice last shared a common ancestor roughly six million years ago, a divergence that is contemporaneous with their hosts. In an assemblage where lice are often highly host specific, humans host two different genera of lice, one that is shared with chimpanzees and another that is shared with gorillas. In this study, we reconstruct the evolutionary history of primate lice and infer the historical events that explain the current distribution of these lice on their primate hosts. RESULTS: Phylogenetic and cophylogenetic analyses suggest that the louse genera Pediculus and Pthirus are each monophyletic, and are sister taxa to one another. The age of the most recent common ancestor of the two Pediculus species studied matches the age predicted by host divergence (ca. 6 million years), whereas the age of the ancestor of Pthirus does not. The two species of Pthirus (Pthirus gorillae and Pthirus pubis) last shared a common ancestor ca. 3-4 million years ago, which is considerably younger than the divergence between their hosts (gorillas and humans, respectively), of approximately 7 million years ago. CONCLUSION: Reconciliation analysis determines that there are two alternative explanations that account for the current distribution of anthropoid primate lice. The more parsimonious of the two solutions suggests that a Pthirus species switched from gorillas to humans. This analysis assumes that the divergence between Pediculus and Pthirus was contemporaneous with the split (i.e., a node of cospeciation) between gorillas and the lineage leading to chimpanzees and humans. Divergence date estimates, however, show that the nodes in the host and parasite trees are not contemporaneous. Rather, the shared coevolutionary history of the anthropoid primates and their lice contains a mixture of evolutionary events including cospeciation, parasite duplication, parasite extinction, and host switching. Based on these data, the coevolutionary history of primates and their lice has been anything but parsimonious. PMID- 17343750 TI - TAMEE: data management and analysis for tissue microarrays. AB - BACKGROUND: With the introduction of tissue microarrays (TMAs) researchers can investigate gene and protein expression in tissues on a high-throughput scale. TMAs generate a wealth of data calling for extended, high level data management. Enhanced data analysis and systematic data management are required for traceability and reproducibility of experiments and provision of results in a timely and reliable fashion. Robust and scalable applications have to be utilized, which allow secure data access, manipulation and evaluation for researchers from different laboratories. RESULTS: TAMEE (Tissue Array Management and Evaluation Environment) is a web-based database application for the management and analysis of data resulting from the production and application of TMAs. It facilitates storage of production and experimental parameters, of images generated throughout the TMA workflow, and of results from core evaluation. Database content consistency is achieved using structured classifications of parameters. This allows the extraction of high quality results for subsequent biologically-relevant data analyses. Tissue cores in the images of stained tissue sections are automatically located and extracted and can be evaluated using a set of predefined analysis algorithms. Additional evaluation algorithms can be easily integrated into the application via a plug-in interface. Downstream analysis of results is facilitated via a flexible query generator. CONCLUSION: We have developed an integrated system tailored to the specific needs of research projects using high density TMAs. It covers the complete workflow of TMA production, experimental use and subsequent analysis. The system is freely available for academic and non-profit institutions from http://genome.tugraz.at/Software/TAMEE. PMID- 17343751 TI - The impact of radiotherapy in the treatment of desmoid tumours. An international survey of 110 patients. A study of the Rare Cancer Network. AB - PURPOSE: A multi-centre study to assess the value of combined surgical resection and radiotherapy for the treatment of desmoid tumours. PATIENTS AND METHODS: One hundred and ten patients from several European countries qualified for this study. Pathology slides of all patients were reviewed by an independent pathologist. Sixty-eight patients received post-operative radiotherapy and 42 surgery only. Median follow-up was 6 years (1 to 44). The progression-free survival time (PFS) and prognostic factors were analysed. RESULTS: The combined treatment with radiotherapy showed a significantly longer progression-free survival than surgical resection alone (p smaller than 0.001). Extremities could be preserved in all patients treated with combined surgery and radiotherapy for tumours located in the limb, whereas amputation was necessary for 23% of patients treated with surgery alone. A comparison of PFS for tumour locations proved the abdominal wall to be a positive prognostic factor and a localization in the extremities to be a negative prognostic factor. Additional irradiation, a fraction size larger than or equal to 2 Gy and a total dose larger than 50 Gy to the tumour were found to be positive prognostic factors with a significantly lower risk for a recurrence in the univariate analysis. This analysis revealed radiotherapy at recurrence as a significantly worse prognostic factor compared with adjuvant radiotherapy. The addition of radiotherapy to the treatment concept was a positive prognostic factor in the multivariate analysis. CONCLUSION: Postoperative radiotherapy significantly improved the PFS compared to surgery alone. Therefore it should always be considered after a non-radical tumour resection and should be given preferably in an adjuvant setting. It is effective in limb preservation and for preserving the function of joints in situations where surgery alone would result in deficits, which is especially important in young patients. PMID- 17343752 TI - Africa and the global carbon cycle. AB - The African continent has a large and growing role in the global carbon cycle, with potentially important climate change implications. However, the sparse observation network in and around the African continent means that Africa is one of the weakest links in our understanding of the global carbon cycle. Here, we combine data from regional and global inventories as well as forward and inverse model analyses to appraise what is known about Africa's continental-scale carbon dynamics. With low fossil emissions and productivity that largely compensates respiration, land conversion is Africa's primary net carbon release, much of it through burning of forests. Savanna fire emissions, though large, represent a short-term source that is offset by ensuing regrowth. While current data suggest a near zero decadal-scale carbon balance, interannual climate fluctuations (especially drought) induce sizeable variability in net ecosystem productivity and savanna fire emissions such that Africa is a major source of interannual variability in global atmospheric CO2. Considering the continent's sizeable carbon stocks, their seemingly high vulnerability to anticipated climate and land use change, as well as growing populations and industrialization, Africa's carbon emissions and their interannual variability are likely to undergo substantial increases through the 21st century. PMID- 17343753 TI - Tissue Harvester with Functional Valve (THFV): Shidham's device for reproducibly higher specimen yield by fine needle aspiration biopsy with easy to perform steps. AB - BACKGROUND: Fine needle aspiration biopsy (FNAB) cytology has been a highly effective methodology for tissue diagnosis and for various ancillary studies including molecular tests. In addition to other benefits, FNAB predominantly retrieves the diagnostic loosely cohesive cells in the lesion as compared to the adjacent supporting stroma with relatively higher cohesiveness. However, FNAB procedure performed with currently available resources is highly skill dependent with inter-performer variability, which compromises its full potential as a diagnostic tool. In this study we report a device overcoming these limitations. METHODS: 'Tissue Harvester with Functional Valve' (THFV) was evaluated as part of a phase 1 National Institute of Health (NIH) research grant under Small Business Technology Transfer (STTR) Program. Working prototypes of the device were prepared. Each of the four cytopathologists with previous cytopathology fellowship training and experience in performing FNAB evaluated 5 THFV and 5 hypodermic needles resulting in 40 specimens (20 with THFV, 20 with hypodermic needles). A piece of fresh cattle liver stuffed in latex glove was used as the specimen. Based on these results a finished design was finalized. RESULTS: The smears and cell blocks prepared from the specimens obtained by THFV were superior in terms of cellularity to specimens obtained with hypodermic needles. The tissuecrit of specimens obtained with THFV ranged from 70 to 100 microl (mean 87, SD 10), compared to 17 to 30 microl (mean 24, SD 4) with conventional hypodermic needles (p < .0001, Student t-test). The technical ease [on a scale of 1 (easy) to 5 (difficult)] with THFV ranged from 1 to 2 as compared to 2 to 3 with hypodermic needles. CONCLUSION: The specimen yield with the new THFV was significantly higher when compared to hypodermic needles. Also, the FNAB procedure with THFV was relatively easier in comparison with hypodermic needles. The final version of Shidham's THFV device would improve the FNAB specimen yield by eliminating the skill factor. The increased specimen yield by this device would also facilitate wider application of FNAB specimens for various ancillary tests, including molecular tests. PMID- 17343754 TI - Adverse childhood experiences and mental health in young adults: a longitudinal survey. AB - BACKGROUND: Adverse childhood experiences (ACEs) have been consistently linked to psychiatric difficulties in children and adults. However, the long-term effects of ACEs on mental health during the early adult years have been understudied. In addition, many studies are methodologically limited by use of non-representative samples, and few studies have investigated gender and racial differences. The current study relates self-reported lifetime exposure to a range of ACEs in a community sample of high school seniors to three mental health outcomes depressive symptoms, drug abuse, and antisocial behavior-two years later during the transition to adulthood. METHODS: The study has a two-wave, prospective design. A systematic probability sample of high school seniors (N = 1093) was taken from communities of diverse socioeconomic status. They were interviewed in person in 1998 and over the telephone two years later. Gender and racial differences in ACE prevalence were tested with chi-square tests. Each mental health outcome was regressed on one ACE, controlling for gender, race/ethnicity, and SES to obtain partially standardized regression coefficients. RESULTS: Most ACEs were strongly associated with all three outcomes. The cumulative effect of ACEs was significant and of similar magnitude for all three outcomes. Except for sex abuse/assault, significant gender differences in the effects of single ACEs on depression and drug use were not observed. However, boys who experienced ACEs were more likely to engage in antisocial behavior early in young adulthood than girls who experienced similar ACEs. Where racial/ethnic differences existed, the adverse mental health impact of ACEs on Whites was consistently greater than on Blacks and Hispanics. CONCLUSION: Our sample of young adults from urban, socio economically disadvantaged communities reported high rates of adverse childhood experiences. The public health impact of childhood adversity is evident in the very strong association between childhood adversity and depressive symptoms, antisocial behavior, and drug use during the early transition to adulthood. These findings, coupled with evidence that the impact of major childhood adversities persists well into adulthood, indicate the critical need for prevention and intervention strategies targeting early adverse experiences and their mental health consequences. PMID- 17343755 TI - Radiation of the Tnt1 retrotransposon superfamily in three Solanaceae genera. AB - BACKGROUND: Tnt1 was the first active plant retrotransposon identified in tobacco after nitrate reductase gene disruption. The Tnt1 superfamily comprises elements from Nicotiana (Tnt1 and Tto1) and Lycopersicon (Retrolyc1 and Tlc1) species. The study presented here was conducted to characterise Tnt1-related sequences in 20 wild species of Solanum and five cultivars of Solanum tuberosum. RESULTS: Tnt1 related sequences were amplified from total genomic DNA using a PCR-based approach. Purified fragments were cloned and sequenced, and clustering analysis revealed three groups that differ in their U3 region. Using a network approach with a total of 453 non-redundant sequences isolated from Solanum (197), Nicotiana (140) and Lycopersicon (116) species, it is demonstrated that the Tnt1 superfamily can be treated as a population to resolve previous phylogenetic multifurcations. The resulting RNAseH network revealed that sequences group according to the Solanaceae genus, supporting a strong association with the host genome, whereas tracing the U3 region sequence association characterises the modular evolutionary pattern within the Tnt1 superfamily. Within each genus, and irrespective of species, nearly 20% of Tnt1 sequences analysed are identical, indicative of being part of an active copy. The network approach enabled the identification of putative "master" sequences and provided evidence that within a genus these master sequences are associated with distinct U3 regions. CONCLUSION: The results presented here support the hypothesis that the Tnt1 superfamily was present early in the evolution of Solanaceae. The evidence also suggests that the RNAseH region of Tnt1 became fixed at the host genus level whereas, within each genus, propagation was ensured by the diversification of the U3 region. Different selection pressures seemed to have acted on the U3 and RNAseH modules of ancestral Tnt1 elements, probably due to the distinct functions of these regions in the retrotransposon life cycle, resulting in both co evolution and adaptation of the element population with its host. PMID- 17343757 TI - Lack of influence of GTP cyclohydrolase gene (GCH1) variations on pain sensitivity in humans. AB - OBJECTIVES: To assess the effect of variations in GTP cyclohydrolase gene (GCH1) on pain sensitivity in humans. METHODS: Thermal and cold pain sensitivity were evaluated in a cohort of 735 healthy volunteers. Among this cohort, the clinical pain responses of 221 subjects after the surgical removal of impacted third molars were evaluated. Genotyping was done for 38 single nucleotide polymorphisms (SNPs) whose heterozygosity > 0.2 in GCH1. Influence of the genetic variations including SNPs and haplotypes on pain sensitivity were analyzed. RESULTS: Minor allele frequencies and linkage disequilibrium show significant differences in European Americans, African Americans, Hispanic Americans and Asian Americans. Association analyses in European Americans do not replicate the previously reported important influence of GCH1 variations on pain sensitivity. CONCLUSION: Considering population stratification, previously reported associations between GCH1 genetic variations and pain sensitivity appear weak or negligible in this well characterized model of pain. PMID- 17343756 TI - Developmental expression of the receptor for advanced glycation end-products (RAGE) and its response to hyperoxia in the neonatal rat lung. AB - BACKGROUND: The receptor for advanced glycation end products (mRAGE) is associated with pathology in most tissues, while its soluble form (sRAGE) acts as a decoy receptor. The adult lung is unique in that it expresses high amounts of RAGE under normal conditions while other tissues express low amounts normally and up-regulate RAGE during pathologic processes. We sought to determine the regulation of the soluble and membrane isoforms of RAGE in the developing lung, and its expression under hyperoxic conditions in the neonatal lung. RESULTS: Fetal (E19), term, 4 day, 8 day and adult rat lung protein and mRNA were analyzed, as well as lungs from neonatal (0-24 hrs) 2 day and 8 day hyperoxic (95% O2) exposed animals. mRAGE transcripts in the adult rat lung were 23% greater than in neonatal (0-24 hrs) lungs. On the protein level, rat adult mRAGE expression was 2.2-fold higher relative to neonatal mRAGE expression, and adult sRAGE protein expression was 2-fold higher compared to neonatal sRAGE. Fetal, term, 4 day and 8 day old rats had a steady increase in both membrane and sRAGE protein expression evaluated by Western Blot and immunohistochemistry. Newborn rats exposed to chronic hyperoxia showed significantly decreased total RAGE expression compared to room air controls. CONCLUSION: Taken together, these data show that rat pulmonary RAGE expression increases with age beginning from birth, and interestingly, this increase is counteracted under hyperoxic conditions. These results support the emerging concept that RAGE plays a novel and homeostatic role in lung physiology. PMID- 17343758 TI - Slum health: diseases of neglected populations. AB - BACKGROUND: Urban slums, like refugee communities, comprise a social cluster that engenders a distinct set of health problems. With 1 billion people currently estimated to live in such communities, this neglected population has become a major reservoir for a wide spectrum of health conditions that the formal health sector must deal with. DISCUSSION: Unlike what occurs with refugee populations, the formal health sector becomes aware of the health problems of slum populations relatively late in the course of their illnesses. As such, the formal health sector inevitably deals with the severe and end-stage complications of these diseases at a substantially greater cost than what it costs to manage non-slum community populations. Because of the informal nature of slum settlements, and cultural, social, and behavioral factors unique to the slum populations, little is known about the spectrum, burden, and determinants of illnesses in these communities that give rise to these complications, especially of those diseases that are chronic but preventable. In this article, we discuss observations made in one slum community of 58,000 people in Salvador, the third largest city in Brazil, to highlight the existence of a spectrum and burden of chronic illnesses not likely to be detected by the formal sector health services until they result in complications or death. Lack of health-related data from slums could lead to inappropriate and unrealistic allocation of health care resources by the public and private providers. Similar misassumptions and misallocations are likely to exist in other nations with large urban slum populations. SUMMARY: Continued neglect of ever-expanding urban slum populations in the world could inevitably lead to greater expenditure and diversion of health care resources to the management of end-stage complications of diseases that are preventable. A new approach to health assessment and characterization of social-cluster determinants of health in urban slums is urgently needed. PMID- 17343759 TI - Microneurolysis and decompression of long thoracic nerve injury are effective in reversing scapular winging: long-term results in 50 cases. AB - BACKGROUND: Long thoracic nerve injury leading to scapular winging is common, often caused by closed trauma through compression, stretching, traction, direct extrinsic force, penetrating injury, or neuritides such as Parsonage-Turner syndrome. We undertook the largest series of long thoracic nerve decompression and neurolysis yet reported to demonstrate the usefulness of long thoracic nerve decompression. METHODS: Winging was bilateral in 3 of the 47 patients (26 male, 21 female), yielding a total of 50 procedures. The mean age of the patients was 33.4 years, ranging from 24-57. Causation included heavy weight-lifting (31 patients), repetitive throwing (5 patients), deep massage (2 patients), repetitive overhead movement (1 patient), direct trauma (1 patient), motor bike accident (1 patient), and idiopathic causes (9 patients). Decompression and microneurolysis of the long thoracic nerve were performed in the supraclavicular space. Follow-up (average of 25.7 months) consisted of physical examination and phone conversations. The degree of winging was measured by the operating surgeon (RKN). Patients also answered questions covering 11 quality-of-life facets spanning four domains of the World Health Organization Quality of Life questionnaire. RESULTS: Thoracic nerve decompression and neurolysis improved scapular winging in 49 (98%) of the 50 cases, producing "good" or "excellent" results in 46 cases (92%). At least some improvement occurred in 98% of cases that were less than 10 years old. Pain reduction through surgery was good or excellent in 43 (86%) cases. Shoulder instability affected 21 patients preoperatively and persisted in 5 of these patients after surgery, even in the 5 patients with persistent instability who experienced some relief from the winging itself. CONCLUSION: Surgical decompression and neurolysis of the long thoracic nerve significantly improve scapular winging in appropriate patients, for whom these techniques should be considered a primary modality of functional restoration. PMID- 17343760 TI - Soluble RAGE but not endogenous secretory RAGE is associated with albuminuria in patients with type 2 diabetes. AB - BACKGROUND: Total circulating soluble receptor for advanced glycation endproducts (sRAGE) and a more defined endogenous secretory splice variant of the receptor (esRAGE) were shown to be associated with different markers of cardiovascular risk in patients with diabetes. Since previous data were partly divergent, the aim of this study was to compare sRAGE and esRAGE in a head-to-head analysis in patients with type 2 diabetes (T2DM) with albuminuria. METHODS: sRAGE and esRAGE were studied in plasma of 110 T2DM patients using enzyme-linked immunosorbant assays (ELISA) detecting either sRAGE or esRAGE only. Both sRAGE and esRAGE were compared with regard to applicability as markers for vascular disease and glucose control in T2DM. RESULTS: In bivariate analysis, sRAGE correlated with age (R = 0.22, p = 0.02) and the 24 hour albumin excretion rate (R = 0.18, p = 0.05), while esRAGE correlated positively with age only (R = 0.23, p = 0.02). In contrast to previous reports, neither sRAGE nor esRAGE correlated with glucose control or intima-media-thickness (IMT) as a predictor of macrovascular disease. In multivariate regression models, the associations between sRAGE and albuminuria as well as esRAGE and age were shown to be independent of glucose control, diabetes duration, body-mass index, glomerular filtration rate, blood pressure and gender. CONCLUSION: This is the first study comparing sRAGE and esRAGE as markers of vascular complications in patients with T2DM. sRAGE but not esRAGE is independently associated with albuminuria in these patients while neither sRAGE nor esRAGE are associated with markers of glucose control or macrovascular disease. PMID- 17343761 TI - Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle control. AB - The retinoblastoma (Rb) tumor suppressor gene product, pRb, has an established role in the implementation of cellular senescence, the state of irreversible G1 cell cycle arrest provoked by diverse oncogenic stresses. In murine cells, senescence cell cycle arrest can be reversed by subsequent inactivation of pRb, indicating that pRb is required not only for the onset of cellular senescence, but also for the maintenance of senescence program in murine cells. However, in human cells, once pRb is fully activated by p16INK4a, senescence cell cycle arrest becomes irreversible and is no longer revoked by subsequent inactivation of pRb, suggesting that p16INK4a/Rb-pathway activates an alternative mechanism to irreversibly block the cell cycle in human senescent cells. Here, we discuss the molecular mechanism underlying the irreversibility of senescence cell cycle arrest and its potential towards tumor suppression. PMID- 17343762 TI - Characterization of Escherichia coli MG1655 grown in a low-shear modeled microgravity environment. AB - BACKGROUND: Extra-cellular shear force is an important environmental parameter that is significant both medically and in the space environment. Escherichia coli cells grown in a low-shear modeled microgravity (LSMMG) environment produced in a high aspect rotating vessel (HARV) were subjected to transcriptional and physiological analysis. RESULTS: Aerobic LSMMG cultures were grown in rich (LB) and minimal (MOPS + glucose) medium with a normal gravity vector HARV control. Reproducible changes in transcription were seen, but no specific LSMMG responsive genes were identified. Instead, absence of shear and a randomized gravity vector appears to cause local extra-cellular environmental changes, which elicit reproducible cellular responses. In minimal media, the majority of the significantly up- or down-regulated genes of known function were associated with the cell envelope. In rich medium, most LSMMG down-regulated genes were involved in translation. No observable changes in post-culture stress responses and antibiotic sensitivity were seen in cells immediately after exposure to LSMMG. Comparison with earlier studies of Salmonella enterica serovar Typhimurium conducted under similar growth conditions, revealed essentially no similarity in the genes that were significantly up- or down-regulated. CONCLUSION: Comparison of these results to previous studies suggests that different organisms may dramatically differ in their responses to medically significant low-shear and space environments. Depending on their specific response, some organisms, such as Salmonella, may become preadapted in a manner that predisposes them to increased virulence. PMID- 17343763 TI - Vascular endothelial growth factor as a non-invasive marker of pulmonary vascular remodeling in patients with bronchitis-type of COPD. AB - BACKGROUND: Several studies have indicated that one of the most potent mediators involved in pulmonary vascular remodeling is vascular endothelial growth factor (VEGF). This study was designed to determine whether airway VEGF level reflects pulmonary vascular remodeling in patients with bronchitis-type of COPD. METHODS: VEGF levels in induced sputum were examined in 23 control subjects (12 non smokers and 11 ex-smokers) and 29 patients with bronchitis-type of COPD. All bronchitis-type patients performed exercise testing with right heart catheterization. RESULTS: The mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) after exercise were markedly increased in all bronchitis-type patients. However, both parameters after exercise with breathing of oxygen was significantly lower than in those with breathing of room air. To attenuate the effect of hypoxia-induced pulmonary vasoconstriction during exercise, we used the change in mPAP or PVR during exercise with breathing of oxygen as a parameter of pulmonary vascular remodeling. Change in mPAP was significantly correlated with VEGF level in induced sputum from patients with chronic bronchitis (r = 0.73, p = 0.0001). Moreover, change in PVR was also correlated with VEGF level in those patients (r = 0.57, p = 0.003). CONCLUSION: A close correlation between magnitude of pulmonary hypertension with exercise and VEGF level in bronchitis-type patients could be observed. Therefore, these findings suggest the possibility that VEGF level in induced sputum is a non invasive marker of pulmonary vascular remodeling in patients with bronchitis-type of COPD. PMID- 17343764 TI - Virtual Interactive Musculoskeletal System (VIMS) in orthopaedic research, education and clinical patient care. AB - The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the "Virtual Human" reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of these unique database and simulation technology. This integrated system, model library and database will impact on orthopaedic education, basic research, device development and application, and clinical patient care related to musculoskeletal joint system reconstruction, trauma management, and rehabilitation. PMID- 17343765 TI - Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms. AB - BACKGROUND: Identifying syntenic regions, i.e., blocks of genes or other markers with evolutionary conserved order, and quantifying evolutionary relatedness between genomes in terms of chromosomal rearrangements is one of the central goals in comparative genomics. However, the analysis of synteny and the resulting assessment of genome rearrangements are sensitive to the choice of a number of arbitrary parameters that affect the detection of synteny blocks. In particular, the choice of a set of markers and the effect of different aggregation strategies, which enable coarse graining of synteny blocks and exclusion of micro rearrangements, need to be assessed. Therefore, existing tools and resources that facilitate identification, visualization and analysis of synteny need to be further improved to provide a flexible platform for such analysis, especially in the context of multiple genomes. RESULTS: We present a new tool, Cinteny, for fast identification and analysis of synteny with different sets of markers and various levels of coarse graining of syntenic blocks. Using Hannenhalli-Pevzner approach and its extensions, Cinteny also enables interactive determination of evolutionary relationships between genomes in terms of the number of rearrangements (the reversal distance). In particular, Cinteny provides: i) integration of synteny browsing with assessment of evolutionary distances for multiple genomes; ii) flexibility to adjust the parameters and re-compute the results on-the-fly; iii) ability to work with user provided data, such as orthologous genes, sequence tags or other conserved markers. In addition, Cinteny provides many annotated mammalian, invertebrate and fungal genomes that are pre loaded and available for analysis at http://cinteny.cchmc.org. CONCLUSION: Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances. Cinteny can also be used to interactively browse syntenic blocks conserved in multiple genomes, to facilitate genome annotation and validation of assemblies for newly sequenced genomes, and to construct and assess phylogenomic trees. PMID- 17343766 TI - Extra-adrenal regeneration of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1: physiological regulator and pharmacological target for energy partitioning. AB - The major glucocorticoid in man, cortisol, plays important roles in regulating fuel metabolism, energy partitioning and body fat distribution. In addition to the control of cortisol levels in blood by the hypothalamic-pituitary-adrenal axis, intracellular cortisol levels within target tissues can be controlled by local enzymes. 11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyses the regeneration of active cortisol from inert cortisone, thereby amplifying cortisol levels and glucocorticoid receptor activation in adipose tissue, liver and other tissues. 11Beta-HSD1 is under complex tissue-specific regulation and there is evidence that it adjusts local cortisol concentrations independently of the plasma cortisol concentrations, e.g. in response to changes in diet. In obesity 11beta-HSD1 mRNA and activity in adipose tissue are increased. The mechanism of this up-regulation remains uncertain; polymorphisms in the HSD11B1 gene have been associated with metabolic complications of obesity, including hypertension and type 2 diabetes, but not with obesity per se. Extensive data have been obtained in mice with transgenic over-expression of 11beta-HSD1 in liver and adipocytes, targeted deletion of 11beta-HSD1, and using novel selective 11beta-HSD1 inhibitors; these data support the use of 11beta-HSD1 inhibitors to lower intracellular glucocorticoid levels and treat both obesity and its metabolic complications. Moreover, in human subjects the non-selective 'prototype' inhibitor carbenoxolone enhances insulin sensitivity. Results of clinical studies with novel potent selective 11beta-HSD1 inhibitors are therefore eagerly awaited. The present article focuses on the physiological role of glucocorticoids in regulating energy partitioning, and the evidence that this process is modulated by 11beta-HSD1 in human subjects. PMID- 17343767 TI - Secondary prevention of CHD in UK men: the Diet and Reinfarction Trial and its sequel. AB - The Diet and Reinfarction Trial (DART) involved 2033 men (mean age 56.5 years) recovering from myocardial infarction. They were randomly allocated to receive advice or to receive no advice on each of three dietary factors: an increase in fatty fish intake; a reduction in fat intake with an increase in polyunsaturated fat:saturated fat; an increased intake of cereal fibre. Compliance was satisfactory with the fish and fibre advice, but less so with the fat advice. The men given fish advice had 29% lower 2-year all-cause mortality; the other forms of advice did not have any significant effects. The Diet and Angina Randomized Trial (DART-2) involved 3114 men (mean age 61.1 years) with stable angina, who were followed up for 3-9 years. Advice to eat oily fish or take fish oil did not affect all-cause mortality, but it was associated with a significant increase in sudden cardiac death (P=0.018), and this effect was largely confined to the subgroup given fish oil capsules. Advice to eat more fruit and vegetables had no effect, probably because of poor compliance. The outcome of DART-2 appears to conflict with that of DART and some other studies; various possible explanations are considered. Nutritional interventions are not equally acceptable and should be tailored to the individuals for whom they are intended. Various distinct groups have a raised risk of CHD, and it cannot be assumed that the same nutritional interventions are appropriate to them all. Nutritional supplements do not necessarily have the same effects as the foods from which they are derived. PMID- 17343768 TI - Nutritional interventions in critical illness. AB - The metabolism of critical illness is characterised by a combination of starvation and stress. There is increased production of cortisol, catecholamines, glucagon and growth hormone and increased insulin-like growth factor-binding protein-1. Phagocytic, epithelial and endothelial cells elaborate reactive oxygen and nitrogen species, chemokines, pro-inflammatory cytokines and lipid mediators, and antioxidant depletion ensues. There is hyperglycaemia, hyperinsulinaemia, hyperlactataemia, increased gluconeogenesis and decreased glycogen production. Insulin resistance, particularly in relation to the liver, is marked. The purpose of nutritional support is primarily to save life and secondarily to speed recovery by reducing neuropathy and maintaining muscle mass and function. There is debate about the optimal timing of nutritional support for the patient in the intensive care unit. It is generally agreed that the enteral route is preferable if possible, but the dangers of the parenteral route, a route of feeding that remains important in the context of critical illness, may have been over emphasised. Control of hyperglycaemia is beneficial, and avoidance of overfeeding is emphasised. Growth hormone is harmful. The refeeding syndrome needs to be considered, although it has been little studied in the context of critical illness. Achieving energy balance may not be necessary in the early stages of critical illness, particularly in patients who are overweight or obese. Protein turnover is increased and N balance is often negative in the face of normal nutrient intake; optimal N intakes are the subject of some debate. Supplementation of particular amino acids able to support or regulate the immune response, such as glutamine, may have a role not only for their potential metabolic effect but also for their potential antioxidant role. Doubt remains in relation to arginine supplementation. High-dose mineral and vitamin antioxidant therapy may have a place. PMID- 17343769 TI - Nutrition interventions in women in low-income groups in the UK. AB - In the UK the mental and physical health and well-being of millions of women are influenced by living in poverty. Low educational attainment, unemployment, low pay and poor areas of residence exacerbate the challenges of obtaining optimal food choices, dietary intake and healthy eating patterns. Poorer women are more likely to eat low amounts of fruits and vegetables, whole grains and fish, and higher amounts of sugar and sweetened drinks compared with more affluent women. Diet contributes to the health inequalities evident in high rates of diet-related morbidity (including obesity) and mortality (including IHD and stroke) and in maternal and child health considerations (including breast-feeding and family diet practices). There is a dearth of research on effective interventions undertaken with low-income women, reflecting some of the challenges of engaging and evaluating programmes with this 'hard to reach' subpopulation. Intervention programmes from the USA, including WISEWOMAN, the Women's Health Initiative, the American Special Supplemental Food Program for Women, Infants and Children and the Expanded Food and Nutrition Education Program provide models for changing behaviour amongst women in the UK, although overall effects of such programmes are fairly modest. Lack of evidence does not mean that that policy work should be not be undertaken, but it is essential that policy work should be evaluated for its ability to engage with target groups as well as for the behavioural change and health outcomes. PMID- 17343770 TI - High-fat diet, muscular lipotoxicity and insulin resistance. AB - A high dietary fat intake and low physical activity characterize the current Western lifestyle. Dietary fatty acids do not stimulate their own oxidation and a surplus of fat is stored in white adipose tissue, liver, heart and muscle. In these organs intracellular lipids serve as a rapidly-available energy source during, for example, physical activity. However, under conditions of elevated plasma fatty acid levels and high dietary fat intake, conditions implicated in the development of modern diseases such as obesity and type 2 diabetes mellitus, fat accumulation in liver and muscle (intramyocellular lipids; IMCL) is associated with the development of insulin resistance. Recent data suggest that IMCL are specifically harmful when combined with reduced mitochondrial function, both conditions that characterize type 2 diabetes. In the (pre)diabetic state reduced expression of the transcription factor PPARgamma co-activator-1alpha (PGC 1alpha), which is involved in mitochondrial biogenesis, has been suggested to underlie the reduced mitochondrial function. Importantly, the reduction in PGC 1alpha may be a result of low physical activity, consumption of high-fat diets and high plasma fatty acid levels. Mitochondrial function can also be impaired as a result of enhanced mitochondrial damage by reactive oxygen species. Fatty acids in the vicinity of mitochondria are particularly prone to lipid peroxidation. In turn, lipid peroxides can induce oxidative damage to mitochondrial RNA, DNA and proteins. The mitochondrial protein uncoupling protein 3, which is induced under high-fat conditions, may serve to protect mitochondria against lipid-induced oxidative damage, but is reduced in the prediabetic state. Thus, muscular lipotoxicity may impair mitochondrial function and may be central to insulin resistance and type 2 diabetes mellitus. PMID- 17343771 TI - Dietary and genetic modulation of DNA repair in healthy human adults. AB - The DNA in all cells of the human body is subject to damage continuously from exogenous agents, internal cellular processes and spontaneous decomposition. Failure to repair such damage is fundamental to the development of many diseases and to ageing. Fortunately, the vast majority of DNA damage is detected and repaired by one of five complementary DNA repair systems. However, recent studies have shown that even in healthy individuals there is a wide inter-individual variation in DNA repair capacity. Part of this variation can be accounted for by polymorphisms in the genes encoding DNA repair proteins. However, it is probable that environmental factors, including dietary exposure as well as diet-gene interactions, are also responsible for much of the difference in repair capacity between individuals. Whilst there is some evidence from human studies that generalised malnutrition or low intakes of specific nutrients may affect DNA repair, as yet there is limited understanding of the molecular mechanisms through which nutrients can modulate this key cellular process. PMID- 17343772 TI - Metabolic interaction of dietary sugars and plasma lipids with a focus on mechanisms and de novo lipogenesis. AB - The elevation of blood lipid concentrations in response to the consumption of low fat high-carbohydrate diets is known as carbohydrate-induced hypertriacylglycerolaemia (HPTG). An understanding of the mechanisms involved in the interaction between carbohydrates and plasma lipids may help determine whether carbohydrate-induced HPTG would increase cardiovascular risk. There is growing evidence to suggest that the sugar component of the diet may be largely responsible, rather than the total carbohydrate. In most studies designed to investigate the mechanisms of carbohydrate-induced HPTG, the amounts and types of sugars and starches used in the diets are not specified. Findings have been mixed and inconsistent. It is proposed that the elucidation of mechanisms from current studies could have been confounded by the different ways in which sugars are metabolized in the body. At present, there are few studies that have evaluated the independent effects of dietary sugars. Interest has been focused on de novo lipogenesis (DNL), as it has recently been found to be positively correlated with increases in fasting TAG levels produced on high-carbohydrate diets, indicating that DNL may contribute to carbohydrate-induced HPTG. DNL has been found to be determined by starch:sugar in a high-carbohydrate diet and affected by different types of sugars. The presence of DNL in adipose tissue is supported by emerging gene-expression studies in human subjects. In the wake of rising intakes of sugars, further research is needed to investigate the mechanisms associated with different sugars, so that appropriate therapeutic strategies can be adopted. PMID- 17343773 TI - The impact of EPA and DHA on blood lipids and lipoprotein metabolism: influence of apoE genotype. AB - Fish and fish oil-rich sources of long-chain n-3 fatty acids have been shown to be cardio-protective, through a multitude of different pathways including effects on arrhythmias, endothelial function, inflammation and thrombosis, as well as modulation of both the fasting and postprandial blood lipid profile. To date the majority of studies have examined the impact of EPA and DHA fed simultaneously as fish or fish oil supplements. However, a number of recent studies have compared the relative biopotency of EPA v. DHA in relation to their effect on blood lipid levels. Although many beneficial effects of fish oils have been demonstrated, concern exists about the potential deleterious impact of EPA and DHA on LDL cholesterol, with a highly-heterogenous response of this lipid fraction reported in the literature. Recent evidence suggests that apoE genotype may be in part responsible. In the present review the impact of EPA and DHA on cardiovascular risk and the blood lipoprotein profile will be considered, with a focus on the apoE gene locus as a possible determinant of lipid responsiveness to fish oil intervention. PMID- 17343774 TI - Effect of cooking brassica vegetables on the subsequent hydrolysis and metabolic fate of glucosinolates. AB - The protective effects of brassica vegetables against cancer may be partly related to their glucosinolate content. Glucosinolates are hydrolysed by plant myrosinase following damage of plant tissue. Isothiocyanates are one of the main groups of metabolites of glucosinolates and are implicated in the preventive effect against cancer. During cooking of brassica the glucosinolate-myrosinase system may be modified as a result of inactivation of plant myrosinase, loss of enzymic cofactors such as epithiospecifier protein, thermal breakdown and/or leaching of glucosinolates and their metabolites or volatilisation of metabolites. Cooking brassica affects the site of release of breakdown products of glucosinolates, which is the upper gastrointestinal tract following consumption of raw brassica containing active plant myrosinase. After consumption of cooked brassica devoid of plant myrosinase glucosinolates are hydrolysed in the colon under the action of the resident microflora. Feeding trials with human subjects have shown that hydrolysis of glucosinolates and absorption of isothiocyanates are greater following ingestion of raw brassica with active plant myrosinase than after consumption of the cooked plant with denatured myrosinase. The digestive fate of glucosinolates may be further influenced by the extent of cell rupture during ingestion, gastrointestinal transit time, meal composition, individual genotype and differences in colonic microflora. These sources of variation may partly explain the weak epidemiological evidence relating consumption of brassica to prevention against cancer. An understanding of the biochemical changes occurring during cooking and ingestion of brassica may help in the design of more robust epidemiological studies to better evaluate the protective effects of brassica against cancer. PMID- 17343775 TI - Mechanisms of the components of the metabolic syndrome that predispose to diabetes and atherosclerotic CVD. AB - The metabolic syndrome represents a summation of obesity-driven risk factors for atherosclerotic CVD and type 2 diabetes. Definitions of the syndrome vary but in general agree closely in identifying subjects. The relationships between the metabolic syndrome and atherosclerotic CVD and diabetes also vary, with relative risks of approximately 1.5-3.0 and approximately 3.0-5.0 respectively. Insulin resistance appears to explain much of the pathophysiology of the syndrome. Both increased fatty acid flux and an excess of circulating pro-inflammatory cytokines are likely mediators. With increased waist circumference, increases in fatty acid delivery to the liver result in higher rates of hepatic glucose production and increases in the secretion of apoB-containing lipoproteins. Concomitant changes in HDL ensue, including a replacement of the cholesterol content with TAG, an accelerated clearance from the plasma and thus a reduced number of HDL particles. Typically also present are increases in small dense LDL. Hypertension in part relates to the insulin resistance, but may involve other mechanisms. Impaired fasting glucose often relates to defects in insulin secretion in addition to insulin resistance, and probably more than any other component of the syndrome predicts the increased incidence of type 2 diabetes. Although not included in the diagnostic criteria, increases in pro-inflammatory cytokines and pro-thrombotic factors, in addition to decreases in plasma adiponectin, may also contribute to the increased incidence of atherosclerotic CVD and diabetes. In general, the greater the number of metabolic syndrome components, the greater the risk for these outcomes. The cytokines and pro-thrombotic factors also appear to contribute. PMID- 17343776 TI - Sensory processing in the brain related to the control of food intake. AB - Complementary neurophysiological recordings in rhesus macaques (Macaca mulatta) and functional neuroimaging in human subjects show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs. Different neurons respond to different combinations, providing a rich representation of the sensory properties of food. In the orbitofrontal cortex feeding to satiety with one food decreases the responses of these neurons to that food, but not to other foods, showing that sensory-specific satiety is computed in the primate (including the human) orbitofrontal cortex. Consistently, activation of parts of the human orbitofrontal cortex correlates with subjective ratings of the pleasantness of the taste and smell of food. Cognitive factors, such as a word label presented with an odour, influence the pleasantness of the odour, and the activation produced by the odour in the orbitofrontal cortex. Food intake is thus controlled by building a multimodal representation of the sensory properties of food in the orbitofrontal cortex and gating this representation by satiety signals to produce a representation of the pleasantness or reward value of food that drives food intake. Factors that lead this system to become unbalanced and contribute to overeating and obesity are described. PMID- 17343777 TI - Cues to overeat: psychological factors influencing overconsumption. AB - Human food intake is driven by necessity, but modern industrialized societies are characterized by food surfeit and an increasingly 'obesogenic' environment. This environment tends to discourage energy expenditure and to facilitate energy intake. The amount eaten in any given eating episode depends less on internal need state and more on environmental contextual factors such as the availability of highly-palatable energy-dense foods. In addition, the process of satiation can easily be disrupted by the introduction within a meal of different foods (variety effect), the presence of others (social context) and competing tasks (distraction). Properties of ingestants such as alcohol promote food intake and characteristics of individuals make them more or less susceptible to situational cues to overeat. In the present review the role of each of these environmental factors in promoting overconsumption are considered and the extent to which these factors might contribute to long-term weight regulation is discussed. PMID- 17343778 TI - Brain responses to obesogenic diets and diet-induced obesity. AB - Rodent models of diet-induced obesity (DIO) mimic common human obesity more accurately than obese single-gene mutation lines, such as the ob/ob mouse. Sprague-Dawley rats sourced in the UK develop obesity when fed a high-energy diet, but susceptibility to DIO is normally distributed, as might be anticipated for a polygenic trait in an outbred population, in contrast to reports in the literature using ostensibly the same strain of rats sourced in the USA. Nevertheless, the responses of these rats to solid and liquid obesogenic diets are very similar to those reported elsewhere, and this model of DIO has much to commend it as a vehicle for the mechanistic study of susceptibility to DIO, development and reversal of obesity on solid and liquid diets and the response of peripheral and central energy balance systems to the development of obesity and to the obesogenic diets themselves. In general, hypothalamic energy-balance related systems respond to obesogenic diets and developing obesity with activity changes that appear designed to counter the further development of the obese state. However, these hypothalamic changes are apparently unable to maintain body weight and composition within normal limits, suggesting that attributes of the obesogenic diets either evade the normal regulatory systems and/or engage with reward pathways that override the homeostatic systems. Since diets are a risk factor in the development of obesity, it will be important to establish how obesogenic diets interact with energy-balance pathways and whether there is potential for diets to be manipulated with therapeutic benefit. PMID- 17343779 TI - Peripheral tissue-brain interactions in the regulation of food intake. AB - More than 70 years ago the glucostatic, lipostatic and aminostatic hypotheses proposed that the central nervous system sensed circulating levels of different metabolites, changing feeding behaviour in response to the levels of those molecules. In the last 20 years the rapid increase in obesity and associated pathologies in developed countries has involved a substantial increase in the knowledge of the physiological and molecular mechanism regulating body mass. This effort has resulted in the recent discovery of new peripheral signals, such as leptin and ghrelin, as well as new neuropeptides, such as orexins, involved in body-weight homeostasis. The present review summarises research into energy balance, starting from the original classical hypotheses proposing metabolite sensing, through peripheral tissue-brain interactions and coming full circle to the recently-discovered role of hypothalamic fatty acid synthase in feeding regulation. Understanding these molecular mechanisms will provide new pharmacological targets for the treatment of obesity and appetite disorders. PMID- 17343780 TI - [Inhibitory effects of RNA interference on MyD88 expression and biological activity in murine myeloid dendritic cells]. AB - AIM: To investigate inhibitory effects of RNA interference on MyD88 expression in murine myeloid dendritic cells(DCs) and detect the biological activity of DCs. METHODS: Three pairs of myeloid differentiation factor 88(MyD88) siRNA were synthesized and transfected into DCs by RNAi-mate. The mRNA and protein expression of MyD88 were analyzed by semi-quantified RT-PCR and Western blot. Mouse DCs were divided into control group and RNA interference group. One of the highest effective siRNA was transfected into RNA interference group. 12 hours later, LPS of the final concentrations of 1.0 mg/L was added in two groups and continued to culture for 3 days. The phenotype and functional properties of DCs were detected by flow cytometry and mixed lymphocyte reaction (MLR). The concentration of TNF-alpha, IFN-gamma and IL-12 in the supernatant was detected by ELISA, and the concentration of NF-kappaB was detected by immunochemistry. RESULTS: mRNA and protein expression were reduced 90% and 85% in sequence2 siRNA, 92% and 88% in sequence3 siRNA respectively but no change was found in other groups. LPS stimulation increased the expression of CD80, CD86 and MHC-II in the cytomembrane of DCs, the concentration of TNF-alpha, IFN-gamma and IL-12 in the supernatant in control group. Besides, LPS stimulation promoted the shift of NF kappaB to karyon and the proliferation of allogeneic T cells in control group. RNA interference inhibited these effects induced by LPS. CONCLUSION: RNA interference can reduce MyD88 expression in murine myeloid dendritic cells and inhibit the maturation of DCs, which may provide a new strategy of gene therapy for related diseases. PMID- 17343781 TI - [The effect of morin on activation, proliferation and cell-cycle of murine T lymphocytes in vitro]. AB - AIM: To discover the effects of morin on the activation, proliferation and cell cycle of murine T lymphocytes in vitro. METHODS: Murine lymph node-derived T lymphocytes were separated and stimulated with concanavalin A (ConA) and different experimental groups were set by co-cultured with morin of different final concentration. Flow cytometry (FCM) was used to detect the activation, proliferation [carboxylfluorescein diacetate, succinimide ester (CFDA-SE) staining] and cell-cycle [propidium iodide(PI) staining] of T cells. RESULTS: After 6 h time of culture in vitro, the rate of CD69(+) T cells in control group was (2.97+/-0.12)%, while it was significant higher in ConA group [(72.52+/ 0.66)% (P<0.01)]. Morin could down-regulate this rate at final concentration being 25, 50 and 100 micromol/L, with a peak at 100 micromol/L morin [(48.95+/ 0.81)% (P<0.01)]. CFDA-SE staining showed that at 48 h and 72 h, the proliferation indexes (PI) of T cells in ConA group were (1.58+/-0.04) and (1.95+/-0.02), respectively. Morin could significantly decrease the PI value at all experimental concentration, with the peak effect at 100 micromol/L morin, which the PI for 48 h was (1.02+/-0.02) and (1.03+/-0.01) for 72 h (P<0.01). FCM analysis of PI staining implied that the percentage of S phase cells in ConA group was (27.05+/-0.39)%, significantly higher than that in control group (5.10+/-0.07)%; and the 25 and 50 micromol/L morin groups showed higher S phase cell rates. CONCLUSION: Morin can significantly inhibit ConA stimulated activation and proliferation of murine T lymphocytes, in which the S phase lagging may serve as one of the major mechanisms. PMID- 17343782 TI - [Establishment of cell line transfected with human BTLA gene and preliminary study on its biological function]. AB - AIM: To establish 293T cells expressing human BTLA gene, a novel attenuator for B and T lymphocyte. METHODS: The gene encoding human BTLA was amplified by RT-PCR from PHA activated T cells, and then the target gene fragment was inserted into retrovirus vector pEGZ-Term after being digested with EcoR I and BamH I. The recombinant vector was transfected into 293T cells with LipfectAMINE 2000, and the cells was further selected with Zeocin. Effect of 293T/BTLA cells on T cells proliferation and activation in vitro was been studied by methods of MTT and cytometry. RESULTS: The stable expression of human BTLA on the transfected cell line was identified by flow cytometry analysis. In vitro, 293T/BTLA cells had an inhibitory effect on the proliferation of T cells stimulated by anti-CD3 mAb and down-regulated the expression of activation marker CD25 on the surface of T cells and decreased the secretion of IFN-gamma and IL-10. CONCLUSION: A cell line 293T/BTLA stably expressing the human BTLA protein has been obtained and it can partially inhibit the proliferation and activation of T cells in vitro. PMID- 17343783 TI - [Experimental study of IFN-alpha and IFN-gamma on reversing ATRA-resistance in MR2 cell line]. AB - AIM: To explore the possibility and the possible mechanism of reversing ATRA resistance in MR2 cells by using IFN-alpha and IFN-gamma in combination with all trans retinoic acid (ATRA). METHODS: After MR2 cells(ATRA-resistance cell line) were treated with IFN-alpha, IFN-gamma and ATRA alone or IFN-alpha and IFN-gamma in combination with ATRA respectively, the cell proliferation was tested by MTT colorimetry, the cell differentiation was tested through light microscope, by NBT test and flow cytometry (FCM). The expression of promyelocytic leukemia (PML) protein was observed by indirect immunofluorescence staining. RESULTS: Both IFN alpha and IFN-gamma could inhibit the proliferation of MR2 cells. The effects were more obviously in both IFN-alpha+ATRA group and IFN-gamma+ATRA group. But there were no significant difference between either IFN-alpha group and IFN-gamma group or IFN-alpha+ATRA group and IFN-gamma+ATRA group (P>0.05). Both IFN could also induce the differentiation of MR2 cells. The effects of IFN-alpha+ATRA group and IFN-gamma+ATRA group were more obvious. However, the differentiation of MR2 cells induced by IFN-gamma+ATRA group was more higher than that by IFN-alpha+ATRA group (P<0.05). Both IFN could induce the expression of PML protein. CONCLUSION: The reversing effcet of IFN-gamma+ATRA group on ATRA-resistence in MR2 cells are more powerful than that of IFN-alpha+ATRA group, which may be related to the different signal transduction pathway of IFN-alpha and IFN-gamma. PMID- 17343784 TI - [Immune response and protective efficacy in BALB/c mice induced by DNA vaccine encoding immunogenic protein of Legionella pneumophila]. AB - AIM: To study the immune response in mice induced by DNA vaccine encoding immunogenic protein of Lgeionella pneumophila (LP) and to examine its protective efficacy against LP in mice. METHODS: The eukaryotic expression recombinant plasmid of LP immunogenic protein gene (pcDNA3.1-ip) was constructed and used to immunize BALB/c female mice intramuscularly, and antigen specific antibodies, lymphocyte proliferative response, IFN-gamma production and cytotoxic T lymphocyte response of the immunized mice were detected. The BALB/c mice immunized by the pcDNA3.1-ip repeatedly were then challenged with LP (10 LD(50)), and the number of survivors in each group was quantitated. Then the mice were sacrificed and lung tissue were harvested for quantitative culture of LP and observation of the pathologic changes. RESULTS: The DNA vaccine pcDNA3.1-ip could induce specific humoral and cellular immunity in the immunized mice. The results indicated that the immunogenicity of pcDNA3.1-ip was higher than that of pcDNA3.1(+) (P<0.01). The vaccine was effective in protecting mice against infection after LP (10 LD(50)) challenge. CONCLUSION: The DNA vaccine encoding immunogenic protein of LP can be used as a candidate for novel vaccine design. PMID- 17343785 TI - [Development of recombinant HEK293-16 cell strain expressing chimera receptor EpoR/LR-F3/HAb18GEF with site-specific integration expression system]. AB - AIM: To establish recombinant HEK293-16 cell strain expressing chimera receptor EpoR/LR-F3/HAb18GEF via site-specific integration expression system. METHODS: The HAb18GEF gene fragment was amplified by PCR and digested with Sac I/Not I, and then cloned into the multiple clone site downstream of EpoR/LR-F3 gene of eukaryotic expression vector pCEL2f. The obtained pCEL2f/HAb18GEF vector, checked by partial nucleotide sequencing and restriction endonuclease digestion, was co transfected with POG44 vector into HEK293-16 cells by mixing with Lipofect AMINE2000 reagent. After selection with hygromycin B for one month, transient and stable expression of EpoR/LR-F3/HAb18GEF were detected by indirect immunofluorescence staining, flow cytometry assay, and Zeocin test. RESULTS: The recombinant pCEL2f/HAb18GEF vector, containing fused EpoR/LR-F3/HAb18GEF gene with correct open reading frame, was successfully constructed. It was confirmed that both EpoR and HAb18GEF were expressed efficiently on the membrane of co transfeced HEK293-16 cells. 12 stably-expressed clones, sensitive to Zeocin, were finally obtained, which presented 99.93% EpoR-positive cells with strong immunofluorescence intensity of 1036.39, and simultaneously presented 99.51% HAb18GEF-positive cells with strong immunofluorescence intensity of 652.72. CONCLUSION: HEK293-16 cell strains stably expressing EpoR/LR-F3/HAb18GEF chimera receptor have been developed successfully, which lays foundation for MAPPIT (Mammalian protein-protein interaction trap) screening of binding molecule of hepatoma associated antigen HAb18G/CD147. PMID- 17343786 TI - [Construction and expression of recombinant eucaryotic expression plasmid of amastin gene of Leishmania Donovani]. AB - AIM: To construct recombinant eukaryotic expression plasmid of amastin gene of Leishmania Donovani and detect expression of the gene in NIH3T3 cells. METHODS: Amastin gene was amplified from nuclear DNA of Leishmania Donovani isolates and cloned into an eukaryotic expression vector pcDNA3.1(+). The recombinant plasmid was named pcDNA3.1-amastin. NIH3T3 cell was transfected by pcDNA3.1-amastin. Transient and stable expression of amastin gene were detected by immunofluoresence and RT-PCR. RESULTS: It was found that there was high green fluorescence on the cell membrane and inside the cell. It showed that NIH3T3 cell was transfected by pcDNA3.1-amastin successfully. CONCLUSION: A recombinant eukaryotic expression plasmid of amastin gene of Leishmania Donovani was successfully constructed, and can be expressed stably in the NIH3T3 cells. PMID- 17343787 TI - [Cloning, expression and identification of human interleukin-10 gene]. AB - AIM: To construct a prokaryotic expression vector containing human interleukin-10 (IL-10) gene, express and identify the protein. METHODS: Human IL-10 gene from HepG2 was isolated and identified by DNA sequencing, and then cloned into the expression vector PET-28 a (+) to construct prokaryotic expression vector. The recombinant protein was expressed in BL21(DE3) and identified by Western blot and ELISA. RESULTS: The expressed protein was mainly located in the inclusion body. The relative molecular mass of the expressed product was identical to that of prediction. The expressed protein had binding activity with specific antibody. CONCLUSION: The human IL-10 gene was successfully cloned and expressed in E.coli. The expressed product had antigenicity which provides foundation for preparation of monoclonal antibodies against IL-10. PMID- 17343788 TI - [Promotion of the activity of Akt in CD8+ T cells by the crosslink of 3H3, an agonist antibody of 4-1BB]. AB - AIM: To investigate whether 4-1BB could promote the proliferation and survival of CD8(+) T cells proliferation, and the activity of protein kinase B (Akt). METHODS: Highly purified CD8(+) T cells were separated and stimulated by CD3 antibody. The crosslink of 3H3 and the proliferation and antiapoptosis of CD8(+) T cells were examined. RESULTS: The crosslink of 3H3 promoted the proliferation and survival of CD8(+) T cells. 4-1BB induced by 3H3 promoted the phosphorylated level and kinase activity of Akt. CONCLUSION: Akt pathway might participate in 4 1BB which promoted the proliferation and survival of CD8(+) T cells induced by 3H3. PMID- 17343789 TI - [Single nucleotide polymorphisms study of surfactant protein A gene between Tibet Sherpas and Guangdong Chinese Hans]. AB - AIM: To investigate the relationship between single nucleotide polymorphisms(SNPs) of surfactant protein A(SP-A) gene of Chinese Han and Sherpas and their adaptation to high altitude hypoxia. METHODS: The genotypes of 90 Chinese Han in Guangdong and 104 Sherpas in Tibet were analyzed by sequence special primer polymerase chain reaction(SSP-PCR) sequencing the surfactant protein A gene. RESULTS: The frequencies of genotypes and alleles at SP-A1 1544 locus showed no difference between the Sherpas and the Chinese Han (P>0.05). However, the frequencies of genotypes C/C, C/T and T/T at SP-A1 3241 locus were 75.0%, 22.1% and 2.9%, respectively in Sherpas, difference to Han population, they were 50.0%, 35.6% and 14.4%, respectirely(P<0.05). Whilst in Sherpas allele frequencies of C and T were 86.1% and 13.9% respectively but they were 67.8% and 32.2% respectively in the Chinese Han(P<0.05); The frequencies of C/C, A/C and A/A at SP-A2 3265 locus were 37.5%, 53.8%, and 8.7%, respectively in the Sherpas were also difference to Chinese Han, they were 63.3%, 30.0%, and 6.7%, respectively. Whilst allele frequencies of C and A were 64.4% and 35.6% in Sherpas but 78.3% and 21.7% in Chinese Han, which showed statistically difference between two groups(P<0.05). CONCLUSION: There were statistically differences of genotypes and alleles at SP-A2 3265 locus in Hans and Sherpas. SNP in SP-A2 at 3265 may be related to the adaptation of Sherpas to high altitude hypoxia. PMID- 17343790 TI - [Primary study of the recombinant immunotoxin DT390-mRantes in EAE therapy]. AB - AIM: To construct a novel eukaryotic expression plasmid including the recombinant immunotoxin DT390-mRantes and treat experimental autoimmune encephalomyelitis (EAE) in mice. METHODS: EAE in C57BL/6 mice were induced by the extracted MBP. The mRantes fragment was inserted into the eukaryotic expression plasmid SRalpha containing DT390. Then cationic liposome-embedded plasmid DNA was injected into the muscles of the hind-limbs in mice. The effect of DT390-mRantes was evaluated by observing clinical symptoms, pathological changes of brain, relative cytokine of peripheral blood, and the proportion of T cells and B cells. RESULTS: The recombinant immunotoxin DT390-mRantes was successfully constructed. Compared the mice in treated group with those in untreated group the clinical symptoms of EAE were alleviated, the infiltration of inflammatory cells were decreased, the IFN gamma level was fallen, and the ratio of T/B cells was decreased. CONCLUSION: The recombinant immunotoxin DT390-mRantes has distinct effects on EAE in mice, which may be used for beneficial reference to the therapy of MS. PMID- 17343791 TI - [The effects of sinomenine on the expresssion of ICAM-1 and IL-2 during the rejection of rat cardiac allograft]. AB - AIM: To observe the pathological characteristics of the rejection of rat cardiac allograft, study the effects and mechanisms of sinomenine on the rejection of rat cardiac allograft. METHODS: The rat model of heterotopic cardiac allograft was established. The rats were randomly divided into four groups: Group A(control group of healthy SD rats), Group B (cardiac allograft of SD to SD rats), Group C (cardiac allograft of SD to Wistar rats) and Group D (sinomenine treated group of cardiac allograft of SD to Wistar rats). ELISA and immunohistochemical staining were carried out to estimate the expression level of IL-2 and ICAM-1 in the grafts. RESULTS: Little ICAM-1 and IL-2 was observed in both Group A and Group B and the infiltration of lymphocytes was not so obvious. In group C, ICAM-1 and IL 2 were increased significantly and the infiltration of lymphocytes was obviously. In group D, inflammatory reaction and infiltration of lymphocytes were much less than those in group C, and ICAM-1 and IL-2 is expressed weakly. CONCLUSION: The expression level of ICAM-1 and IL-2 was relevant to the occurrence and development of graft rejection. Sinomenine could obviously reduce the expression of intercellular adhesion molecule and the infiltration of lymphocytes in the grafts and prolong grafts survival significantly. PMID- 17343792 TI - [Expression and biological function of ULBP4 in Rosetta-gamiTMB(DE3) and mAb preparation]. AB - AIM: To express human ULBP4 in Rosetta-gami(TM) B(DE3) and to prepare monoclonal antibody against ULBP4 for the research of gamma deltaT cells recognition mechanism. METHODS: DNA fragments of ULBP4 were derived from HO-8910 RNA by reverse-transcriptase polymerase chain reaction(RT-PCR). The fragments encoding the former 225 amino acids of ULBP4 were cloned into Histag fusion protein expression vector pET22b(+). The C-Histag fusion ULBP4(225a) protein was expressed in inclusion body and purified step by step according to manufactory's protocol and renatured in bag filter. It's functional effect on NK cells was evaluated by NKG2D binding assay and IFN-gamma secretion experiments. Prokaryotic expressed human ULBP4 was used as an antigen to prepare monoclonal antibodies by means of the B lymphocyte hybridoma technique. RESULTS: ULBP4 recombinant protein can stimulate NK cells to secrete IFN-gamma. Through PEG fusion and screening by limited dilution, we obtained four strains of hybridoma cells secreting anti ULBP4 antibodies. CONCLUSION: The fusion protein was expressed successfully and functional. At the same time, the anti-ULBP4 mAbs were prepared successfully. Both of them provide a platform for further research. PMID- 17343793 TI - [Preparation and characterization of the monoclonal antibody against human soluble mesothelin-related proteins]. AB - AIM: To prepare the monoclonal antibody (mAb) against human soluble mesothelin related proteins (SMR) and identify its properties. METHODS: The B-cell epitopes of mesothelin (MSLN) were predicted by multi-parameter prediction method. Then BALB/c mice were immunized with compound MSLN polypeptide prepare the mAb by hybridoma technique. The specificity of antibody was evaluated by immuocytochemistry and Western blot respectively. RESULTS: Using the multi parameter prediction of B-cell epitopes, the 471-481 epitope domain was selected and synthesized. Then the mice were immunized and mAb against human SMR was prepared and designated 2H10. The specificity of mAb 2H10 was evaluated to be high by using immuocytochemistry and Western blot. CONCLUSION: The successful preparation of the mAb against SMR will provide efficient reagent for further detection of SMR by ELISA. PMID- 17343794 TI - [Preparation and immunological characterization of monoclonal antibodies against VP22 carboxyl terminus of Marek's disease virus serotype 1]. AB - AIM: To prepare and characterize monoclonal antibodies (mAb) against VP22 carboxyl terminus of CVI988/Rispens strain of Marek's disease virus serotype 1. METHODS: Carboxyl terminus of CVI988 VP22 (94aa-243aa) was expressed in prokaryotic system. mAbs against VP22 were prepared by hybridoma technology from BALB/c mice immunized with the fusion protein GST-VP22C and characterized by ELISA, indirect fluorescence assay (IFA) and Western blot. RESULTS: Two hybridoma cell lines stably secreting mAb against VP22C were obtained and designated as 3F7 and 4E4. mAb 3F7 could react with VP22 expressed in all the plaques, while mAb 4E4 stained all the cells nuclei in MDV-infected CEF cells. It was also found that 3F7 could react with VP22 expressed in Sf9 cells and denatured VP22 by Western blot analysis. In addition, it was further showed that the epitope of mAb 3F7 was located within the domain between 94aa and 193aa, the predicted site of protein transduction domain of VP22. CONCLUSION: The preparation of the mAb is very important to further research in protein transduction domain of MDV-1 VP22. PMID- 17343795 TI - [Preparation and primary application of monoclonal antibody against benzylpenicillin]. AB - AIM: To develop monoclonal antibody(mAb) against benzylpenicillin and to establish a Sandwich ELISA method for relative quantitative analysis of the allergen which induced penicillin allergy commonly in clinic. METHODS: Penicillin, as a kind of hapten, was conjugated with carrier protein to form complete antigen and then was used to immunize BALB/c mice. Hybridoma cells secrecting mAb against penicillin were developed. Ascites from the immunized mice were purified by caprylic acid-ammonium sulfate precipitation. The specificity of the purified antibodies was detected and the suitable antibodies were used for establishing Sandwich ELISA. RESULTS: Nine hybridoma cells stably secrecting mAb were prepared through cell fusion, screening and cloning, and five of these purified mAb had relative high affinity. The double-antibody Sandwich ELISA for relative quantitative analysis of benzylpenicilloyl protein was established with a sensitivity of 870 U/L.The average recovery rate was 107.81% and the average intra- and inter-coefficient of varitation (CV) was 6.7% and 9.3% respectively. The method was applied for relative quantitative analysis of benzylpenicilloyl protein from Group A Streptococcus Preparation. CONCLUSION: Nine hybridoma cell strains stably secreting mAb against benzylpenicillin were obtained. The double antibody Sandwich ELISA for relative quantitative analysis of benzylpenicilloyl protein was established. PMID- 17343796 TI - [Apoptotic effect of the combined treatment of engineered antibody with paclitaxel on BT474 cells]. AB - AIM: To explore the apoptotic effect of the combined treatment of anti-p185(c erbB-2/neu) engineered antibody with paclitaxel on p185-overexpressing human malignant breast cancer cell lines BT474 and to study its emerging mechanism. METHODS: The prohibitory effect of engineeded antibody plus paclitaxel on BT474 cells was assessed by MTS assay. The number of apoptotic cells was detected by Annexin V-FITC/PI. DNA content and cell cycle distribution were determined by FCM; DNA-binding activity of NF-kappaB was demonstrated by EMSA. RESULTS: Anti p185(c-erbB-2/neu) engineered antibody plus paclitaxel resulted in synergistic effect on proliferative inhibiton of BT474 cells, which was mediated via apoptotic induction and caused cell cycle to arrest at G1 phase remarkably. Furthermore, the combined treatment of the engineered antibody with paclitaxel effectively suppressed the activation of NF-kappaB in BT474 cells. CONCLUSION: The combined treatment of anti-p185(c-erbB-2/neu) engineered antibody with paclitaxel rendered p185-overexpressing human malignant breast cancer cells BT474 more susceptible to paclitaxel-induced apoptosis by the effective suppression of NF-kappaB activation. PMID- 17343797 TI - [Construction, expression and identification of a single chain antibody variable (scFv) against human CD25 molecule]. AB - AIM: To construct and express a single chain fragment variable (scFv) fragment against human CD25 molecule and identify its bioactivity. METHODS: V(H) and V(L) genes of anti-murine CD25 monoclonal antibody were cloned by RT-PCR from hybridoma cell WuTac secreting anti-CD25 mAb. scFv gene was spliced by sequence overlap extending (SOE) PCR, and then it was ligated into pMD18T vector to be identified by endonuclease digestion, PCR and sequencing. scFv gene was cloned into pBAD/gIIIA expression vector and transformed into TOP10 E.coli. After positive clones were induced by L-arabinose for 4 hours, the purity of protein was detected by SDS-PAGE and its bioactivity was identified by competitive inhibition ELISA test. RESULTS: scFv genes of V(L)-(GGGGSGGGGSSGGGS)-V(H) was constructed successfully. The V(H) chain consisted of 351 bp and encoded 117 amino acids, which belonged to heavy chain subgroup III (C) of mouse immunoglobulin variable region. The V(L) chain consisted of 318 bp and encoded 106 amino acids, which belonged to light chain subgroup IV of mouse immunoglobulin variable region. The scFv antibody expressed by TOP10 fused with 6xHis and C-myc tag protein and the relative molecular mass of fusion protein was about 31,000. Competitive inhibition ELISA test indicated the scFv antibody had specific activity. CONCLUSION: The expressed product of the single-chain antibody shows some specific binding capacity, which provides a basis for the clinical application of anti-CD25 single-chain antibody. PMID- 17343798 TI - [Knockout serum replacement improves establishment efficiency of C57BL/6J mouse embryonic stem cell line]. AB - AIM: To eliminate the influence of serum on self-renewal of embryonic stem cells (ESCs), knockout serum replacement (KSR), a defined formulation, was used to replace serum for the establishment of C57BL/6J mouse ESC line. METHODS: C57BL/6J mouse blastocysts collected at 3.5 days post coitum (d.p.c.) were cultured in the medium supplemented with KSR. In control experiment, KSR was substituted by fetal bovine serum (FBS). When ESC line was established, the morphology of ESCs, the expression of alkaline phosphatase and oct-4, and the karyotype and differentiating ability of ESCs were analyzed. RESULTS: 13 blastocysts were cultured in the medium supplemented with KSR and one ESC line (MES-1) was established with a normal and stable XX karyotype after cultured for more than 20 passages, and then the high expression of alkaline phosphatase and oct-4 was detected. When cultured in suspension, MES-1 formed embryoid bodies. When inoculated subcutaneously into nude mice, MES-1 formed teratoma. After injected into ICR mouse blastocysts collected at 3.5 d.p.c., MES-1 incorporated into the inner cell mass of the host blastocyst and contributed to the development of a chimera. In control experiment, no ESC lines were cultured for more than 3 passages. CONCLUSION: KSR can be efficiently used to isolate and culture C57BL/6J mouse ESCs, which can eliminate traditional prescreening of FBS suitable for isolation and culture of ESCs. PMID- 17343799 TI - A blood-based DNA test for colorectal cancer screening. AB - Early detection of colorectal tumors through the identification of mutant DNA in serum or plasma could have a substantial impact on morbidity and mortality. Somatic mutations are specific biomarkers for neoplastic cells, but their detection requires sensitive assays, as the number of circulating mutant molecules is small compared to the number of normal DNA molecules. A newly developed method can provide this sensitivity and at the same time precisely quantify the fraction of mutant molecules present in the clinical sample. Using this technology, it has been found that more than half of patients with early stage disease contain mutant DNA in their circulation. PMID- 17343800 TI - Genome-wide mutational analyses of breast and colorectal cancers. AB - With the human genome sequence at hand, it is now possible to sequence coding regions of cancer cell genomes to identify the mutated genes that drive tumor formation. The clinical importance of breast and colorectal cancer, together causing 14% of yearly cancer deaths, make these two tumor types suitable initial candidates for cancer genome sequencing. We recently surveyed more than half of the known human genes for somatic mutations in eleven breast and eleven colorectal cancers, and defined 122 and 69 genes, respectively, as candidate cancer genes in these two diseases. The study design provides a blueprint for future cancer genome sequencing efforts, validated by its ability to detect known and novel cancer genes. The findings shed light on heterogeneity between and within tumor types and provide novel research avenues for cancer biology. PMID- 17343801 TI - Targeting stromal cells in chronic inflammation. AB - Why chronic inflammatory reactions persist in specific sites, such as rheumatoid arthritis in the joints, remains a mystery. Current models of inflammation have concentrated upon the responses of lymphocytes such as B and T cells to specific antigens, and have attempted, often unsuccessfully, to address the causative agent. However recent studies have shown that stromal cells such as macrophages, endothelial cells, and fibroblasts play important roles in the switch that turns a spontaneously resolving acute inflammatory response within a tissue into chronic and persistent disease. Therapeutic manipulation of the stromal microenvironment has been particularly effective in treating cancer and is likely to provide novel therapies to achieve improved control of chronic inflammatory disease. PMID- 17343802 TI - Updates on antiviral therapy for chronic hepatitis C. AB - Hepatitis C virus (HCV) infection is a major public health problem around the world and it is estimated that there are about 200 million infections globally. The majority of HCV infected patients develop chronic infection, which can progress to liver cirrhosis, hepatocellular carcinoma, and liver failure. Since the discovery of the virus in 1989, impressive progress has been made in the treatment of HCV hepatitis. However, the actual standard of care in treating HCV infection, represented by the combination therapy of pegylated interferon alpha 2a or 2b with ribavirin, fails to cure near half of treated patients. This paper aimed to trace a brief overview of the progress made by interferon-based treatments for HCV hepatitis since their introduction in the early 1990s, and to highlight the results of recent clinical studies concerning new and emerging drugs. PMID- 17343803 TI - Dietary agents/supplements hit the clinic for prostate cancer chemoprevention. AB - Dietary studies of men throughout the world have identified certain foods/food derived substances that are correlated to prostate cancer risk. While radical modification of cultural dietary habits with the goal of preventing prostate cancer remains challenging, supplementation with certain foods and/or food derived substances identified as having potential chemopreventative properties may be a feasible approach, particularly for Western cultures. Before such chemopreventative strategies can be recommended to patients, their benefits must be rigorously demonstrated in appropriately designed clinical trials. This paper discusses several agents currently under scientific scrutiny for prostate cancer chemopreventative activities and the data available, thus far. PMID- 17343805 TI - Immunological tolerance in the therapy of rheumatoid arthritis. AB - Dramatic progress in the treatment of Rheumatoid Arthritis (RA) has led to an early and aggressive treatment strategy, combining DMARDS with biological agents. Since these therapies are able to induce initial clinical control, attention has shifted toward the maintenance of this state. Tools to maintain long-term remission are still lacking but may be found in the ability to establish immunological tolerance. Tolerance can be induced in several specific and nonspecific ways, including manipulation of costimulatory signals, induction of regulatory T cells, and tolerization to heat shock proteins. Induction of disease control with the current combination therapies, followed by progressive withdrawal in parallel with re-establishing immunological tolerance, may be an attractive approach in the near future. PMID- 17343804 TI - Targeted, gene-directed enzyme prodrug therapies to tackle diversity and aggression of late stage prostate cancer. AB - Late stage hormone refractory prostate cancer (HRPC) is presently incurable. Novel alternatives such as cytoreductive Gene Directed Enzyme Prodrug Therapy (GDEPT) offer great hope: The potential for in situ amplification of cytotoxicity due to GDEPT-associated "bystander effects" has special appeal for patients with prostate cancer, the prostate being dispensable. In this overview, recent developments in various GDEPT systems for treating prostate cancer are described. Research related to the enhancement of in situ GDEPT delivery and prostate cancer targeting of viral vectors, is reviewed. The scope and progress of synergies between GDEPT and other treatment modalities, traditional and alternate, are discussed. PMID- 17343806 TI - Updates on the management of upper gastrointestinal disorders in the primary care setting: NSAID-related gastropathies and pediatric reflux diseases. PMID- 17343807 TI - Virtual colonoscopy: what is its role in cancer screening? PMID- 17343808 TI - Who should get the HPV vaccine? PMID- 17343809 TI - Footprints. PMID- 17343810 TI - Nudulo-cystic eruption with musculoskeletal pain. PMID- 17343811 TI - Diabetes drug update: how 4 new options stack up. PMID- 17343812 TI - Clinical inquiries. Which tests are most useful for diagnosing PID? PMID- 17343813 TI - Clinical inquiries. What's the best test for HSV-2 after exposure? PMID- 17343814 TI - Clinical inquiries. Which UTI therapies are safe and effective during breastfeeding? PMID- 17343815 TI - Clinical inquiries. How effective are hypertension self-care interventions? PMID- 17343816 TI - Clinical inquiries. What's the best treatment for cradle cap? PMID- 17343817 TI - Clinical inquiries. Should you treat a symptomatic patient by phone when his child has confirmed strep throat? PMID- 17343819 TI - A PCR-based technique to construct T-vectors for high-throughput cloning of PCR products. PMID- 17343818 TI - Analysis of read length limiting factors in Pyrosequencing chemistry. AB - Pyrosequencing is a bioluminometric DNA sequencing technique that measures the release of pyrophosphate during DNA synthesis. The amount of pyrophosphate is proportionally converted into visible light by a cascade of enzymatic reactions. Pyrosequencing has heretofore been used for generating short sequence reads (1 100 nucleotides) because certain factors limit the system's ability to perform longer reads accurately. In this study, we have characterized the main read length limiting factors in both three-enzyme and four-enzyme Pyrosequencing systems. A new simulation model was developed to simulate the read length of both systems based on the inhibitory factors in the chemical equations governing each enzymatic cascade. Our results indicate that nonsynchronized extension limits the obtained read length, albeit to a different extent for each system. In the four enzyme system, nonsynchronized extension due mainly to a decrease in apyrase's efficiency in degrading excess nucleotides proves to be the main limiting factor of read length. Replacing apyrase with a washing step for removal of excess nucleotide proves to be essential in improving the read length of Pyrosequencing. The main limiting factor of the three-enzyme system is shown to be loss of DNA fragments during the washing step. If this loss is minimized to 0.1% per washing cycle, the read length of Pyrosequencing would be well beyond 300 bases. PMID- 17343820 TI - Photochemical internalization enhances silencing of epidermal growth factor receptor through improved endosomal escape of siRNA. AB - Photochemical internalization (PCI) has been employed as a tool for site-specific intracellular delivery of a variety of molecules. In this study, for the first time, PCI has been employed to facilitate the endosomal escape of small interfering RNA (siRNA) molecules, which are the functional mediators of RNA interference (RNAi). In order to interact with the machinery that will induce post-transcriptional gene silencing, siRNA molecules need to enter the cytoplasm of the cells. This study shows that one of the important rate-limiting steps of siRNA silencing efficiency is the ability of siRNA molecules and/or complexes to escape from the endosomes into the cytosol of the cells. The target of this study, the epidermal growth factor receptor (EGFR), is known as an attractive target for cancer therapy. In this study, a 10-fold increased efficiency in knockdown of the EGFR protein was obtained when anti-EGFR siRNA treatment was combined with PCI as compared to siRNA treatment alone. The fact that this combined treatment resulted in a stronger silencing efficiency indicates that lower doses of siRNA can be used when PCI is employed to augment siRNA delivery. Lowering doses of siRNA would prevent saturation of the RNAi machinery and reduce off-target effects. In addition, local illumination of target tissue would only induce PCI in the desired cells, which can further increase the specificity of the treatment, supporting PCI as an attractive strategy to improve siRNA silencing efficiency. PMID- 17343821 TI - Implications of naturalistic use of pharmacotherapy in CBT treatment for panic disorder. AB - This study examined naturalistic medication use and cognitive behavioral therapy (CBT) treatment outcomes in 105 patients meeting DSM-IV criteria for panic disorder (PD), assessed by structured clinical interview. The association between pre- and post-treatment use of SSRIs, benzodiazepines (BZs), and any anti-anxiety or anti-depressant (A/D) medication were investigated for three indicators of treatment outcome (PD severity, presence of agoraphobia (AG), anxiety sensitivity) at post-treatment and 6-month follow-up. Controlling for pre treatment severity, pre-treatment SSRI use was associated with worse outcomes for AG (p=.04) and anxiety sensitivity (p=.047); post-treatment SSRI use was associated with delayed improvements in PD severity (p=.05). Pre-treatment use of A/D was associated with poorer PD severity outcomes (p=.04). Post-treatment use of A/D was associated with higher anxiety sensitivity scores across post treatment and 6-month follow-up (p=.03). BZ use was not associated with significantly worse outcomes. However, there was a decrease in the number of patients using BZs from pre-treatment to post-treatment (p=.06) and follow-up (p=.006). In conclusion, controlling for pre-treatment severity, pre- and post treatment use of SSRIs and A/D was associated with poorer outcomes, particularly for PD severity and anxiety sensitivity. PMID- 17343822 TI - Implicit but not explicit self-esteem predicts future depressive symptomatology. AB - To date, research on the predictive validity of implicit self-esteem for depressive relapse is very sparse. In the present study, we assessed implicit self-esteem using the Name Letter Preference Task and explicit self-esteem using the Rosenberg self-esteem scale in a group of currently depressed patients, formerly depressed individuals, and never depressed controls. In addition, we examined the predictive validity of explicit, implicit, and the interaction of explicit and implicit self-esteem in predicting future symptoms of depression in formerly depressed individuals and never depressed controls. The results showed that currently depressed individuals reported a lower explicit self-esteem as compared to formerly depressed individuals and never depressed controls. In line with previous research, all groups showed a positive implicit self-esteem not different from each other. Furthermore, after controlling for initial depressive symptomatology, implicit but not explicit self-esteem significantly predicted depressive symptoms at six months follow-up. Although implicit self-esteem assessed with the Name Letter Preference Test was not different between formerly depressed individuals and never depressed controls, the findings suggest it is an interesting variable in the study of vulnerability for depression relapse. PMID- 17343823 TI - Essential role of the N-terminus of murine Orai1 in store-operated Ca2+ entry. AB - Store-operated Ca(2+) entry (SOCE) is a physiologically important process that is triggered by intracellular Ca(2+) depletion. Recently, human Orai1 (the channel forming subunit) and STIM1 (the calcium sensor) were identified as essential molecules for SOCE. Here, we report the cloning and functional analysis of three murine orthologs of Orai1, termed Orai1, 2, and 3. Among the genes identified, Orai1 contains a distinctive proline- and arginine-rich N-terminal cytoplasmic sequence. Co-expression of STIM1 with Orai1 produced a marked effect on SOCE, while co-expression with Orai2 or Orai3 had little effect. Expression of Orai1 without its N-terminal tail had a marginal effect on SOCE, while chimeric Orai2 containing the Orai1 N-terminus produced a marked increase in SOCE. In addition, a truncated version of Orai1 containing the N-terminus without the pore-forming transmembrane domain had a dominant negative effect on SOCE. These results reveal the essential role of Orai1 and its N-terminal sequence in SOCE. PMID- 17343824 TI - SATB1 regulates SPARC expression in K562 cell line through binding to a specific sequence in the third intron. AB - Special AT-rich binding protein 1 (SATB1), a cell type-specific nuclear matrix attachment region (MAR) DNA-binding protein, tethers to a specific DNA sequence and regulates gene expression through chromatin remodeling and HDAC (histone deacetylase complex) recruitment. In this study, a SATB1 eukaryotic expression plasmid was transfected into the human erythroleukemia K562 cell line and individual clones that stably over-expressed the SATB1 protein were isolated. Microarray analysis revealed that hundreds of genes were either up- or down regulated in the SATB1 over-expressing K562 cell lines. One of these was the extra-cellular matrix glycoprotein, SPARC (human secreted protein acidic and rich in cysteine). siRNA knock-down of SATB1 also reduced SPARC expression, which was consistent with elevated SPARC levels in the SATB1 over-expressing cell line. Bioinformatics software Mat-inspector showed that a 17bp DNA sequence in the third intron of SPARC possessed a high potential for SATB1 binding; a finding confirmed by Chromatin immunoprecipitation (ChIP) with anti-SATB1 antibody. Our results show for the first time that forced-expression of SATB1 in K562 cells triggers SPARC up-regulation by binding to a 17bp DNA sequence in the third intron. PMID- 17343825 TI - Geranylgeranylacetone inhibits ovarian cancer progression in vitro and in vivo. AB - Geranylgeranylacetone (GGA), an isoprenoid compound, is an anti-ulcer drug developed in Japan. In our previous study, GGA was shown to inhibit ovarian cancer invasion by attenuating Rho activation [K. Hashimoto, K. Morishige, K. Sawada, M. Tahara, S. Shimizu, M. Sakata, K. Tasaka, Y. Murata, Geranylgeranylacetone inhibits lysophosphatidic acid-induced invasion of human ovarian carcinoma cells in vitro. Cancer 103 (2005) 1529-1536.]. In the present study, GGA treatment inhibited ovarian cancer progression in vitro and suppressed the tumor growth and ascites in the in vivo ovarian cancer model. In vitro analysis, treatment of cancer cells by GGA resulted in the inhibition of cancer cell proliferation, the inactivation of Ras, and the suppression of tyrosine phosphorylation of mitogen-activated protein kinase (MAPK). In conclusion, this is the first report that GGA inhibited ovarian cancer progression and the anti tumor effect by GGA is, at least in part, derived not only from the suppression of Rho activation but also Ras-MAPK activation. PMID- 17343826 TI - The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF 4alpha. AB - The cytosolic human intestinal fatty acid binding protein (hFABP2) is proposed to be involved in intestinal absorption of long-chain fatty acids. The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4alpha (HNF-4alpha), involved in regulation of genes of fatty acid metabolism and differentiation. Electromobility shift assays demonstrated that HNF-4alpha binds at position -324 to -336 within the hFABP2 promoter. Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4alpha by about 50%. Thus, binding element at position -336/-324 essentially determines the transcriptional activity of promoter and may be important in control of hFABP2 expression by dietary lipids and differentiation. Studying genotype interactions of hFABP2 and HNF-4alpha, that are both candidate genes for diabetes type 2, may be a powerful approach. PMID- 17343827 TI - Oxidation of calmodulin alters activation and regulation of CaMKII. AB - Increases in reactive oxygen species and mis-regulation of calcium homeostasis are associated with various physiological conditions and disease states including aging, ischemia, exposure to drugs of abuse, and neurodegenerative diseases. In aged animals, this is accompanied by a reduction in oxidative repair mechanisms resulting in increased methionine oxidation of the calcium signaling protein calmodulin in the brain. Here, we show that oxidation of calmodulin results in an inability to: (1) activate CaMKII; (2) support Thr(286) autophosphorylation of CaMKII; (3) prevent Thr(305/6) autophosphorylation of CaMKII; (4) support binding of CaMKII to the NR2B subunit of the NMDA receptor; and (5) compete with alpha actinin for binding to CaMKII. Moreover, oxidized calmodulin does not efficiently bind calcium/calmodulin-dependent protein kinase II (CaMKII) in rat brain lysates or in vitro. These observations contrast from past experiments performed with oxidized calmodulin and the plasma membrane calcium ATPase, where oxidized calmodulin binds to, and partially activates the PMCA. When taken together, these data suggest that oxidative stress may perturb neuronal and cardiac function via a decreased ability of oxidized calmodulin to bind, activate, and regulate the interactions of CaMKII. PMID- 17343828 TI - Phylogenomics of caspase-activated DNA fragmentation factor. AB - The degradation of nuclear DNA by DNA fragmentation factor (DFF) is a key step in apoptosis of mammalian cells. Using comparative genomics, we have here determined the evolutionary history of the genes encoding the two DFF subunits, DFFA (also known as ICAD) and DFFB (CAD). Orthologs of DFFA and DFFB were identified in Nematostella vectensis, a representative of the primitive metazoan clade cnidarians, and in various vertebrates and insects, but not in representatives of urochordates, echinoderms, and nematodes. The domains mediating the interaction of DFFA and DFFB, a caspase cleavage site in DFFA, and the amino acid residues critical for endonuclease activity of DFFB were conserved in Nematostella. These findings suggest that DFF has been a part of the primordial apoptosis system of the eumetazoan common ancestor and that the ancient cell death machinery has degenerated in several evolutionary lineages, including the one leading to the prototypical apoptosis model, Caenorhabditis elegans. PMID- 17343829 TI - Glucuronidation of fenamates: kinetic studies using human kidney cortical microsomes and recombinant UDP-glucuronosyltransferase (UGT) 1A9 and 2B7. AB - Mefenamic acid, a non-steroidal anti-inflammatory drug (NSAID), is used commonly to treat menorrhagia. This study investigated the glucuronidation kinetics of flufenamic, mefenamic and niflumic acid using human kidney cortical microsomes (HKCM) and recombinant UGT1A9 and UGT2B7. Using HKCM Michaelis-Menten (MM) kinetics were observed for mefenamic (K(m)(app) 23 microM) and niflumic acid (K(m)(app) 123 microM) glucuronidation, while flufenamic acid exhibited non hyperbolic (atypical) glucuronidation kinetics. Notably, the intrinsic renal clearance of mefenamic acid (CL(int) 17+/-5.5 microL/minmg protein) was fifteen fold higher than that of niflumic acid (CL(int) 1.1+/-0.8 microL/minmg protein). These data suggest that renal glucuronidation of mefenamic acid may result in high intrarenal exposure to mefenamic acyl-glucuronide and subsequent binding to renal proteins. Diverse kinetics were observed for fenamate glucuronidation by UGT2B7 and UGT1A9. Using UGT2B7 MM kinetics were observed for flufenamic (K(m)(app) 48 microM) and niflumic acid (K(m)(app) 135 microM) glucuronidation and atypical kinetics with mefenamic acid. Similarity in K(m)(app) between HKCM and UGT2B7 suggests that UGT2B7 may be the predominant renal UGT isoform catalysing niflumic acid glucuronidation. In contrast, UGT1A9 glucuronidation kinetics were characterised by negative cooperativity with mefenamic (S(50) 449 microM, h 0.4) and niflumic acid (S(50) 7344 microM, h 0.4) while atypical kinetics were observed with flufenamic acid. Additionally, potent inhibition of the renal glucuronidation of the UGT substrate 'probe' 4-methylumbelliferone by flufenamic, mefenamic and niflumic acid was observed. These data suggest that inhibitory metabolic interactions may occur between fenamates and other substrates metabolised by UGT2B7 and UGT1A9 in human kidney. PMID- 17343830 TI - Inhibition of G1/S transition potentiates oxaliplatin-induced cell death in colon cancer cell lines. AB - In a series of colorectal cancer cell lines, both necrosis and apoptosis were induced upon exposure to oxaliplatin, and enhanced by co-administration of the Hsp90 inhibitor 17-AAG. We analyzed the effects of these interventions on the cell cycle, and found that oxaliplatin treatment caused G1 and G2 arrest in HCT116 cells, and S-phase accumulation in two p53-deficient cell lines (HT29 and DLD1). Addition of 17-AAG enhanced cell cycle effects of oxaliplatin in HCT116, and induced G1 arrest and decrease in S-phase population in the other cell lines. Analysis of cell cycle proteins revealed that the major difference between the cell lines was that in HCT116, 17-AAG resulted in profound inhibition of expression and phosphorylation of late G1 proteins cyclin E and cdk2, with no effect on p21/WAF1 induction. Consistent with these, an HCT116 p53(-/-) line, lacking p21, showed resistance to oxaliplatin, failure to enter apoptosis, and an accumulation of cells in S-phase. Introduction of p21 in these cells caused reversal of that phenotype, including restoration of the G1 block and re sensitization to oxaliplatin. Inhibition of G1/S progression using cdk2 inhibitor also enhanced oxaliplatin cytotoxicity. We conclude that in colon cancer cells with impaired p53 function, interventions directed to cycle arrest in G1 may potentiate oxaliplatin activity. PMID- 17343831 TI - Brain histamine and schizophrenia: potential therapeutic applications of H3 receptor inverse agonists studied with BF2.649. AB - BF2.649, a high affinity and selective non-imidazole histamine H(3)-receptor antagonist/inverse agonist, was found to easily enter the brain after oral administration to mice: it displayed a ratio of brain/plasma levels of about 25 when considering either C(max) or AUC values. At low oral doses (2.5-20mg/kg), it elicited in mice a dose-dependent wakening effect accompanied with a shift towards high frequency waves of the EEG, a sign of cortical activation. DOPAC/dopamine ratios were enhanced in the prefrontal cortex but not in the striatum, indicating a selective activation of a sub-population of dopaminergic neurons. BF2.649 showed significant inhibitory activity in several mouse models of schizophrenia. It reduced locomotor hyperactivity elicited by methamphetamine or dizolcipine without significantly affecting spontaneous locomotor activity when administered alone. It also abolished the apomorphine-induced deficit in prepulse inhibition. These observations suggest that H(3)-receptor inverse agonists/antagonists deserve attention as a novel class of antipsychotic drugs endowed with pro-cognitive properties. PMID- 17343832 TI - Glutathione depletion and recovery after acute ethanol administration in the aging mouse. AB - Glutathione (GSH) plays an important role in the detoxification of ethanol (EtOH) and acute EtOH administration leads to GSH depletion in the liver and other tissues. Aging is also associated with a progressive decline in GSH levels and impairment in GSH biosynthesis in many tissues. Thus, the present study was designed to examine the effects of aging on EtOH-induced depletion and recovery of GSH in different tissues of the C57Bl/6NNIA mouse. EtOH (2-5 g/kg) or saline was administered i.p. to mice of ages 6 months (young), 12 months (mature), and 24 months (old); and GSH and cyst(e)ine concentrations were measured 0-24h thereafter. EtOH administration (5 g/kg) depleted hepatic GSH levels >50% by 6h in all animals. By 24h, levels remained low in both young and old mice, but recovered to baseline levels in mature mice. At 6h, the decrease in hepatic GSH was dose-dependent up to 3g/kg EtOH, but not at higher doses. The extent of depletion at the 3g/kg dose was dependent upon age, with old mice demonstrating significantly lower GSH levels than mature mice (P<0.001). Altogether these results indicate that aging was associated with a greater degree of EtOH and fasting-induced GSH depletion and subsequent impaired recovery in liver. An impaired ability to recover was also observed in young animals. Further studies are required to determine if an inability to recover from GSH depletion by EtOH is associated with enhanced toxicity. PMID- 17343833 TI - Effects of chronic opioid exposure on guinea pig mu opioid receptor in Chinese hamster ovary cells: comparison with human and rat receptor. AB - Chronic opioid treatment leads to agonist-specific effects at the mu opioid receptor. The molecular mechanisms resulting from chronic opioid exposure include desensitization, internalization and down-regulation of membrane-bound mu opioid receptors (MOP). The purpose of this study was to compare the cellular regulation of guinea pig, human and rat MOP expressed in Chinese hamster ovary (CHO) cells, following exposure to two clinically important opioids, morphine and methadone. MOP expressing CHO cells were treated in culture with methadone or morphine for up to 48 h. Radioligand diprenorphine and [D-AIa(2),N-Me-Phe(4),Gly(5)-ol] enkephalin (DAMGO)-stimulated GTP gamma S binding assays were carried out using paired control and opioid-exposed CHO cells. Methadone induced downregulation of the mu opioid receptor, while morphine induced desensitization of the receptor for all three species. Furthermore, morphine predominantly decreased the potency of DAMGO to stimulate GTP gamma S binding, whereas methadone primarily reduced its efficacy. Changes in DAMGO potency and efficacy differed among species and depended on the opioid used to treat the cells. Our results showed similarities between guinea pig and human MOP for morphine-induced desensitization, but identified differences between the two for methadone-induced desensitization. In contrast, human and rat MOP differed in response to morphine treatment, but were not distinct in their response to methadone treatment. The guinea pig is an excellent and established animal model to study opioid effects, but its molecular opioid pharmacology has not been investigated thus far. These results can assist in understanding species differences in the effects of opioid ligands activating the mu opioid receptor. PMID- 17343834 TI - Sensitivity of the five-choice serial reaction time task to the effects of various psychotropic drugs in Sprague-Dawley rats. AB - BACKGROUND: Attentional deficits accompany many psychiatric disorders, underscoring the need for rodent models of attention to screen novel therapeutic agents and characterize the biological basis of attention. The five-choice serial reaction time task (5CSRTT) is one such model. Here, we characterized the effects of four standard psychotropic agents on performance in the 5CSRTT. METHODS: Male Sprague-Dawley rats were trained in the 5CSRTT (5-sec inter-trial interval and .5 sec stimulus duration) until they reliably performed at > 60% accuracy and < 20% omissions. They were then treated systemically with the stimulant methylphenidate (MPH) (.063-2.0 mg/kg), the N-methyl-D-aspartate antagonist dizocilpine (MK-801) (.008-.25 mg/kg), the norepinephrine reuptake inhibitor desipramine (DMI) (.63-10 mg/kg), or the kappa-receptor agonist U69,593 (.25-2.0 mg/kg) 30 min before testing. RESULTS: Methylphenidate (.5 mg/kg) increased accuracy. Dizocilpine impaired accuracy (.25 mg/kg), increased premature responses (.063-.25 mg/kg), and increased omissions (.25 mg/kg). Desipramine decreased premature responses (5.0 mg/kg) but increased omissions (10 mg/kg), correct response latencies (5.0 10.0 mg/kg), and reward latencies (5.0-10.0 mg/kg). The kappa-opioid agonist U69,593 (1.0-2.0 mg/kg) increased omissions and correct response latencies. CONCLUSIONS: In Sprague-Dawley rats, psychotropic drugs with distinct pharmacological profiles produced distinguishable effects in the 5CSRTT. The effects of these classes of drugs under our testing conditions are qualitatively similar to their effects in humans. PMID- 17343835 TI - Preferred transport of O-(2-[18F]fluoroethyl)-D-tyrosine (D-FET) into the porcine brain. AB - Amino acids are valuable tracers for brain tumor imaging with positron emission tomography (PET). In this study the transport of O-(2-[(18)F]fluoroethyl)-D tyrosine (D-FET) across the blood-brain barrier (BBB) was studied with PET in anesthetized piglets and patients after subtotal resection of brain tumors and compared with O-(2-[(18)F]fluoroethyl)-L-tyrosine (L-FET) and 3-O-methyl-6 [(18)F]fluoro-L-DOPA (L-OMFD). In piglets, compartmental modeling of PET data was used to calculate the rate constants for the blood-brain (K(1)) and the brain blood (k(2)) transfer of D-FET, L-FET and L-OMFD. In patients standardized uptake values (SUVs) were calculated in brain cortex and lesions. Additionally, affinity determinations on various amino acid transporters (LAT1, LAT2, PAT1, XPCT) were performed in vitro using unlabeled D-FET, L-FET and L-OMFD. The initial brain uptake of D-FET in piglets was more than two-fold higher than that of l-FET, whereas the initial brain uptake of D-FET in patients was similar to that of L FET. Calculation of K(1) and k(2) from the brain uptake curves and the plasma input data in piglets revealed about 4- and 2-fold higher values for D-FET compared to L-FET and L-OMFD, respectively. The distribution volume of D-FET in the piglet brain was slightly higher than that of L-FET as it was also found for most other organs. In brain tumor patients, initial D-FET uptake in the brain was similar to that of L-FET but showed faster tracer washout. L-FET uptake remained rather constant and provided a better delineation of residual tumor than D-FET. In conclusion, our data indicate considerable differences of stereoselective amino acid transport at the BBB in different species. Therefore, the results from animal experiments concerning BBB amino acid transport may not be transferable to humans. PMID- 17343836 TI - Adrenergic control of a constitutively active acetylcholine-regulated potassium current in canine atrial cardiomyocytes. AB - OBJECTIVES: Canine atrial cardiomyocytes display a constitutively active, acetylcholine-regulated, time-dependent K+ current (IKH) that contributes to atrial repolarization and atrial tachycardia-induced atrial-fibrillation promotion. Adrenergic stimulation favors atrial arrhythmogenesis but its effects on IKH are poorly understood. METHODS AND RESULTS: Adrenergic modulation of IKH was studied in isolated canine atrial cardiomyocytes with whole-cell patch clamping, and action-potential consequences were assessed in multicellular preparations with fine-tipped microelectrodes. Isoproterenol increased IKH in a concentration-dependent manner (maximum 103+/-22% increase), an effect mimicked by forskolin and 8-bromo-cyclic AMP. Isoproterenol effects were prevented by propranolol and the selective beta1-adrenoceptor blocker CGP-20712A, but not the beta2-blocker ICI-118551. Isoproterenol enhancement was prevented by pipette administered protein kinase A (PKA) inhibitor peptide or by superfusion of H89 (PKA blocker). Phenylephrine decreased IKH in a reversible, concentration dependent way. This effect was blocked by the alpha-antagonist prazosin and the selective alpha1A-blocker niguldipine, but not the alpha1B-blocker chloroethylclonidine or the alpha1D inhibitor BMY-7378. Phenylephrine effects were prevented by the phospholipase C (PLC) inhibitor U73122 and the protein kinase C (PKC) inhibitor bisindolylmaleimide. The PKC-activating phorbol ester PDD (but not its inactive analogue alpha-PDD) mimicked phenylephrine effects. Action potential recordings in the presence and absence of the selective IKH blocker tertiapin indicated a functional role of alpha- and beta-adrenergic actions on IKH. Adrenergic regulation of cholinergic agonist-induced K+ current paralleled that of IKH. CONCLUSIONS: IKH is under dual regulation by the adrenergic system: beta1-adrenergic stimulation enhances IKH via cAMP-dependent PKA pathways, whereas alpha1A-adrenergic stimulation inhibits IKH via PLC mediated PKC activation. Modulation of constitutive acetylcholine-regulated K+ current is a novel potential mechanism for adrenergic control of atrial repolarization. PMID- 17343837 TI - Future directions in butadiene risk assessment and the role of cross-species internal dosimetry. AB - The 2005 International Symposium on the evaluation of butadiene and chloroprene health risks provided the opportunity to consider the past, present and future state of research issues for 1,3-butadiene. Considerable advancements have been made in our knowledge of exposure, metabolism, biomarkers of exposure and effect, and epidemiology. Despite this, uncertainties remain which will impact the human health risk assessment for current worker and environmental exposures. This paper reviews key aspects of recent studies and the role that biomarkers of internal dosimetry can play in addressing low to high exposure, gender, and cross-species differences in butadiene toxicity and metabolism. Considerable information is now available on the detection and quantification of protein adducts formed from the mono-, di- and dihydroxy-epoxide metabolites of butadiene. The diepoxide metabolite appears to play a key role in mutagenesis. Species differences in production of this critical metabolite are reflected by the diepoxybutane specific hemoglobin adduct, pry-Val. To date, the pry-Val adduct has not been quantifiable in human blood samples from workers with cumulative occupational exposures up to 6.3 ppm-weeks; whereas, the pry-Val was quantifiable in the blood of mice and rats with similar cumulative exposures. Levels in mice were much higher than in rats. Further improvements in analytical sensitivity for the pyr Val adduct are on the horizon. Epidemiology studies are also described and ongoing efforts promise to help bridge our understanding of past and future risks. PMID- 17343839 TI - Learning non-local dependencies. AB - This paper addresses the nature of the temporary storage buffer used in implicit or statistical learning. Kuhn and Dienes [Kuhn, G., and Dienes, Z. (2005). Implicit learning of nonlocal musical rules: implicitly learning more than chunks. Journal of Experimental Psychology-Learning Memory and Cognition, 31(6) 1417-1432] showed that people could implicitly learn a musical rule that was solely based on non-local dependencies. These results seriously challenge models of implicit learning that assume knowledge merely takes the form of linking adjacent elements (chunking). We compare two models that use a buffer to allow learning of long distance dependencies, the Simple Recurrent Network (SRN) and the memory buffer model. We argue that these models - as models of the mind - should not be evaluated simply by fitting them to human data but by determining the characteristic behaviour of each model. Simulations showed for the first time that the SRN could rapidly learn non-local dependencies. However, the characteristic performance of the memory buffer model rather than SRN more closely matched how people came to like different musical structures. We conclude that the SRN is more powerful than previous demonstrations have shown, but it's flexible learned buffer does not explain people's implicit learning (at least, the affective learning of musical structures) as well as fixed memory buffer models do. PMID- 17343838 TI - Adiponectin as an anti-inflammatory factor. AB - Obesity is characterized by low-grade systemic inflammation. Adiponectin is an adipose tissue-derived hormone, which is downregulated in obesity. Adiponectin displays protective actions on the development of various obesity-linked diseases. Several clinical studies demonstrate the inverse relationship between plasma adiponectin levels and several inflammatory markers including C-reactive protein. Adiponectin attenuates inflammatory responses to multiple stimuli by modulating signaling pathways in a variety of cell types. The anti-inflammatory properties of adiponectin may be a major component of its beneficial effects on cardiovascular and metabolic disorders including atherosclerosis and insulin resistance. In this review, we focus on the role of adiponectin in regulation of inflammatory response and discuss its potential as an anti-inflammatory marker. PMID- 17343841 TI - Effect of matrine on HeLa cell adhesion and migration. AB - This study sought to explore the role of matrine in the metastasis of cancer cells and to gain insight into the possible mechanism of matrine's ability to inhibit cancer metastasis. Accordingly, changes in vasodilator-stimulated phosphoprotein (VASP) phosphorylation and in cAMP-dependent protein kinase (PKA) activity during cell detachment and reattachment were first investigated. After administration of matrine (50 microg/ml), the decrease in VASP phosphorylation paralleled the decrease in PKA activity. Matrine was found to significantly inhibit HeLa cell adhesion to collagen I. To determine the effect of matrine on the migration of HeLa cells, we analysed the migratory behaviour of HeLa cells in a two and three-dimensional cell migration assay. In a two-dimensional cell migration assay, the average cell migration velocity was significantly reduced by matrine compared with the control. Moreover, in a three-dimensional cell migration assay performed with the Transwell system, HeLa cells treated with matrine (50 microg/ml) were found to migrate less than the control cells. These data suggest that the inhibitory effect of matrine may be produced by decreased phosphorylation of VASP due to inhibition of the activity of PKA during HeLa cell adhesion and migration. PMID- 17343842 TI - Omapatrilat enhances adrenomedullin's reduction of cardiomyocyte cell death. AB - The objective of this study was to determine whether adrenomedullin, a vasodilator peptide, modulates the process of cell death in cardiomyocytes and whether its effect would be enhanced by the endopeptidase inhibitor omapatrilat, which reduces adrenomedullin degradation. Further, we sought to determine whether the effect of adrenomedullin involved an action to preserve mitochondrial transmembrane potential (DeltaPsi(m)). Cardiomyocytes in culture were treated with agents that interrupted the mitochondrial electron transport chain, inhibiting glycolysis and oxidative phosphorylation. Cell death was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and DeltaPsi(m) was assessed by fluorescent microscopy. Cytochrome c loss from mitochondria and appearance in cytosol was determined by Western blotting. Potassium cyanide (KCN) plus deoxyglucose or antimycin A, for 24 h, produced significant (p<0.01) concentration-dependent reductions in cell viability or increases in cell death. Adrenomedullin reduced cell death produced in this manner and the effect of adrenomedullin was enhanced by treatment with omapatrilat. In contrast, there was no additional reduction in cell death by lisinopril treatment. Omapatrilat plus adrenomedullin reduced the KCN plus deoxyglucose-induced increase in cytosolic cytochrome c. A likely mechanism centers on the ability of adrenomedullin plus omapatrilat to prevent the decline in mitochondrial DeltaPsi(m) produced by KCN plus deoxyglucose treatment. In summary, adrenomedullin plus omapatrilat limited the decline in mitochondrial DeltaPsi(m) that accompanies interruption of mitochondrial metabolism and limited the extent of cell death in cardiomyocytes treated with KCN plus deoxyglucose or antimycin. Adrenomedullin plus the endopeptidase inhibitor omapatrilat may be a useful strategy to protect cardiomyocytes from cell death, in conditions associated with impairment of mitochondrial function. PMID- 17343843 TI - Novel neuroprotective compound SCH-20148 rescues thymocytes and SH-SY5Y cells from thapsigargin-induced mitochondrial membrane potential reduction and cell death. AB - Mitochondrial membrane potential plays an important role in cell survival. Transitions in mitochondrial permeability, which indicate the imminent destruction of the organelles, have been observed in damaged neuronal cells both in vitro and in vivo. In this study, C57/BL6n mouse thymocytes were put under stress using thapsigargin, a Ca2+ ATP-ase inhibitor, after which the change in mitochondrial membrane potential was monitored with a JC-1 dual-emission probe. This was done in an attempt to identify a novel compound that can suppress mitochondrial membrane potential reduction and cell death. In this assay system, the novel compound SCH-20148 [2,3-dihydroxypropyl-5-bromo-N-(2-methyl-3 trifluoromethylphenyl)anthranilate] was found to protect mouse thymocytes against thapsigargin (3 nM)-induced mitochondrial membrane potential reduction (IC50=42 nM). SCH-20148 also prevented A23187- or ionomycin-induced shifts in mitochondrial membrane potential but it did not have any effect on the changes induced by tunicamycin, staurosporine, or dexamethasone. The potent immunosuppressants tacrolimus and cyclosporine A prevented the effect of thapsigargin, but did not prevent the A23187- or ionomycin-induced changes. Calcium-modulating agents, an anti-oxidant, a protein kinase C inhibitor, and anti-inflammatory agents were not effective against thapsigargin-induced mitochondrial permeability transition which implies that SCH-20148 exerts a protective effect via its specific mechanism. In addition, SH-20148 demonstrated a neuroprotective effect against thapsigargin-induced neuronal cell death in neuroblastoma SH-SY5Y cells. Taken together, these results suggest the potential of SCH-20148 as novel neuroprotective drug. PMID- 17343844 TI - The role of cycloxygenase-2 in the rodent kidney following ischaemia/reperfusion injury in vivo. AB - The role of cyclooxygenase-2 (COX-2) in the pathophysiology of renal ischaemia/reperfusion injury is still not fully understood. In order to elucidate the role of COX-2 in ischaemia/reperfusion injury of the kidney, we have evaluated the effects of ischaemia/reperfusion on renal dysfunction and injury in (i) rats treated with either vehicle or the selective COX-2 inhibitor parecoxib, and (ii) wild-type mice or mice in which the gene for COX-2 has been deleted (COX 2 knock-out mice or COX-2(-/-)). Rats were subjected to bilateral renal ischaemia (45 min) and reperfusion (6 h), and received parecoxib (20 mg/kg, i.v.) 30 min prior to ischaemia and 3 h after the commencement of reperfusion. Serum urea, serum creatinine, serum aspartate aminotransferase, creatinine clearance and fractional excretion of sodium were all used as indicators of renal dysfunction and injury. Mice (wild-type and COX-2(-/-)) were subjected to bilateral renal ischaemia (30 min) and reperfusion (24 h) after which renal dysfunction (serum urea and creatinine) and renal injury was assessed by histological analysis. Parecoxib significantly augmented the degree of renal dysfunction and injury caused by ischaemia/reperfusion in the rat. In addition, the degree of renal injury and dysfunction caused by ischaemia/reperfusion was also significantly augmented in COX-2(-/-) mice when compared to their wild-type littermates. These findings support the view that metabolites of COX-2 protect the kidney against ischaemia/reperfusion injury, and (ii) that selective inhibitors of COX-2 may worsen renal dysfunction and injury in conditions associated with renal ischaemia. PMID- 17343845 TI - A Tyr-W-MIF-1 analog containing D-Pro2 discriminates among antinociception in mice mediated by different classes of mu-opioid receptors. AB - The antagonism by Tyr-D-Pro-Trp-Gly-NH2 (D-Pro2-Tyr-W-MIF-1), a Tyr-Pro-Trp-Gly NH2 (Tyr-W-MIF-1) analog, of the antinociception induced by the mu-opioid receptor agonists Tyr-W-MIF-1, [D-Ala2,NMePhe4,Gly(ol)5]-enkephalin (DAMGO), Tyr Pro-Trp-Phe-NH2 (endomorphin-1), and Tyr-Pro-Phe-Phe-NH2 (endomorphin-2) was studied with the mouse tail-flick test. D-Pro2-Tyr-W-MIF-1 (0.5-3 nmol) given intracerebroventricularly (i.c.v.) had no effect on the thermal nociceptive threshold. High doses of D-Pro2-Tyr-W-MIF-1 (4-16 nmol) administered i.c.v. produced antinociception with a low intrinsic activity of about 30% of the maximal possible effect. D-Pro2-Tyr-W-MIF-1 (0.25-2 nmol) co-administered i.c.v. showed a dose-dependent attenuation of the antinociception induced by Tyr-W-MIF-1 or DAMGO without affecting endomorphin-2-induced antinociception. A 0.5 nmol dose of D-Pro2-Tyr-W-MIF-1 significantly attenuated Tyr-W-MIF-1-induced antinociception but not DAMGO- or endomorphin-1-induced antinociception. The highest dose (2 nmol) of D-Pro2-Tyr-W-MIF-1 almost completely attenuated Tyr-W MIF-1-induced antinociception. However, that dose of D-Pro2-Tyr-W-MIF-1 significantly but not completely attenuated endomorphin-1 or DAMGO-induced antinociception, whereas the antinociception induced by endomorphin-2 was still not affected by D-Pro2-Tyr-W-MIF-1. Pretreatment i.c.v. with various doses of naloxonazine, a mu1-opioid receptor antagonist, attenuated the antinociception induced by Tyr-W-MIF-1, endomorphin-1, endomorphin-2, or DAMGO. Judging from the ID50 values for naloxonazine against the antinociception induced by the mu-opioid receptor agonists, the antinociceptive effect of Tyr-W-MIF-1 is extremely less sensitive to naloxonazine than that of endomorphin-1 or DAMGO. In contrast, endomorphin-2-induced antinociception is extremely sensitive to naloxonazine. The present results clearly suggest that D-Pro2-Tyr-W-MIF-1 is a selective antagonist for the mu2-opioid receptor in the mouse brain. D-Pro2-Tyr-W-MIF-1 may also discriminate between Tyr-W-MIF-1-induced antinociception and the antinociception induced by endomorphin-1 or DAMGO, which both show a preference for the mu2 opioid receptor in the brain. PMID- 17343846 TI - Rosiglitazone, a PPARgamma ligand, modulates signal transduction pathways during the development of acute TNBS-induced colitis in rats. AB - Recent studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma), a highly nuclear receptor expressed in the colon, may participate in the control of inflammation, especially in regulating the production of immunomodulatory and inflammatory mediators, cellular proliferation and apoptosis. In order to delve into the anti-inflammatory mechanisms and signalling pathways of PPARgamma agonists, we have studied the effects of rosiglitazone, a PPARgamma agonist on the extent and severity of acute ulcerative colitis caused by intracolonic administration of 2,4,6-trinitribenzene sulfonic acid (TNBS) in rats. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumour necrosis factor alpha (TNF-alpha) levels and a histological study of the lesions. We determined prostaglandin E2 production as well as the cyclooxygenases (COX)-1 and -2 expressions by immunohistochemistry and Western blotting. The nuclear factor kappa (NF-kappaB) p65 and p38 mitogen activated protein kinase (MAPK) expression levels were also measured by Western blotting. Finally, since PPARgamma agonists modulate apoptosis, we tried to clarify its effects under early acute inflammatory conditions. Inflammation following TNBS induction was characterized by increased colonic wall thickness, edema, diffuse inflammatory cells infiltration, necrosis reaching an ulcer index (UI) of 9.66+/-0.66 cm(2) and increased MPO activity and TNF-alpha colonic levels. Rosiglitazone treatment significantly reduced the morphological alteration associated with TNBS administration and the UI with the highest dose. In addition, the degree of neutrophil infiltration and the cytokine levels were significantly ameliorated. Rosiglitazone significantly reduced the rise in the prostaglandin (PG) E(2) generation compared with TNBS group. The COX-1 levels remained stable throughout the treatment in all groups. The COX-2 expression was elevated in TNBS group; however rosiglitazone administration reduced the COX-2 overexpression. A high expression of NF-kappaB p65 and p38 MAPK proteins appeared in colon mucosa from control TNBS-treated rats; nevertheless, PPARgamma agonist treatment drastically decreased them. There were no significant changes in apoptosis after rosiglitazone treatment when compared to TNBS group. In conclusion, rosiglitazone seems to modulate the acute colitis through NF-kappaB p65 and p38 MAPK signalling pathways. PMID- 17343847 TI - Antinociceptive and antiedematogenic activities of fenofibrate, an agonist of PPAR alpha, and pioglitazone, an agonist of PPAR gamma. AB - Peroxisome proliferator activated receptors (PPAR) are ligand-regulated transcription factors that control the expression of many genes. The antiinflammatory activity of fibrates, PPARalpha agonists, and thiazolidinediones, PPARgamma agonists, has been demonstrated in many in vitro and a few in vivo studies. In the present study, we evaluated the effect of acute (100 or 300 mg/kg, p.o.) or prolonged (100 or 300 mg/kg day, 7 days, p.o.) treatment with fenofibrate and acute treatment with pioglitazone (doses ranging from 1 to 50 mg/kg, i.p.), PPARalpha and PPARgamma agonists, respectively, on experimental models of nociception and edema, in order to expand the knowledge of their potential antiinflammatory activities. Fenofibrate and pioglitazone did not inhibit the nociceptive response in the hot-plate model and the first phase of formaldehyde induced nociceptive response in mice. However, treatment with pioglitazone and prolonged treatment with fenofibrate inhibited the second phase of this response. Mechanical allodynia induced by carrageenan in rats was inhibited by prolonged treatment with fenofibrate, but not by acute treatment with pioglitazone or fenofibrate. Both drugs inhibited paw edema induced by carrageenan in rats. Fenofibrate did not inhibit mechanical allodynia or paw edema induced by phorbol-12,13-didecanoate (PDD), a protein kinase C activator, in rats. Pioglitazone inhibited paw edema, but not mechanical allodynia, induced by PDD. The results represent the first demonstration of the antinociceptive and antiedematogenic activities of fenofibrate and pioglitazone and give further support to the potential use of PPAR agonists in the treatment of different inflammatory diseases. PMID- 17343848 TI - RNA interference for HIF-1alpha inhibits foam cells formation in vitro. AB - Macrophage-derived foam cells in atherosclerotic lesions are generally thought to play a major role in the pathology of the disease. Hypoxia-inducible factor 1alpha (HIF-1alpha) was recently found to play an important role in atherosclerosis. Here we applied RNA interference to study the role of HIF-1alpha in foam cell formation in vitro. Transfection of HIF-1alpha-siRNA reduced HIF 1alpha synthesis as measured on mRNA and protein level by real-time RT-PCR, Western blot. It was found that RNA interference for HIF-1alpha with small interfering RNAs (HIF-1alpha-siRNA) inhibits foam cell formation by the human monoblastic cell line (U937) which was treated with oxidized low-density lipoprotein (ox-LDL) while the majority of atherosclerosis-related genes, such as cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1), interleukin 1beta (IL-1beta), and so on, were down-regulated, through large scale gene expression analysis using DNA microarrays. These data demonstrate that induction of HIF-1alpha by atherogenic factors may be a key step in coordinating the cellular events that result in atherosclerotic lesions. PMID- 17343850 TI - GAP-43 expression is upregulated in retinal ganglion cells after ischemia/reperfusion-induced damage. AB - In response to injury, the adult mammalian retina shows signs of structural remodeling, possibly in an attempt to preserve or regain some of its functional neural connections. In order to study the mechanisms involved in injury-induced plasticity, we have studied changes in growth associated protein 43 (GAP-43) after retinal ischemia/reperfusion in the rat. GAP-43 is a marker for neuronal remodeling and is involved in synapse formation. Ischemic injury of the rat retina was induced by 60 min of ischemia followed by reperfusion times varying from 2h up to 4 weeks. GAP-43 mRNA levels were significantly increased between 12h and 72 h reperfusion with a peak around 24h. GAP-43 specific antibodies showed that the total amount of GAP-43 labeling in the inner plexiform layer was diminished after 12h of reperfusion by approximately 35% and remained at this level up to 1 week postischemia despite the reduction in thickness of this layer during this period resulting from the ischemia-induced cell loss. At 2 and 4 weeks reperfusion, the amount of labeling was reduced by 70%, simultaneously with a decrease of GAP-43 transcript level. Between 72 h up to 2 weeks postischemia, the induction of intense GAP-43 labeling was observed in NeuN- and beta-tubulin positive ganglion cell somata and in horizontally and vertically oriented processes in the inner plexiform layer. Ischemia also induced GAP-43 expression in some GFAP-positive Muller cells. Double-labeling showed that in controls and after ischemia GAP-43 was expressed by some amacrine cells of the glycinergic (glycine transporter 1), calretinin-positive, and dopaminergic (tyrosine hydroxylase) subpopulations. No increase of GAP-43 expression levels was found in these amacrine cells. The results demonstrate that ganglion cells show an elevated expression of GAP-43 after ischemia-inflicted damage. These findings suggest a temporal window during which ganglion cells may remodel their neuronal network in the damaged retina. PMID- 17343851 TI - Proteomic surveillance of autoimmunity in Behcet's disease with uveitis: selenium binding protein is a novel autoantigen in Behcet's disease. AB - Autoimmune response to retinal antigens is considered to be one of the pathogenesis of uveitis in Behcet's disease (BD). In the present study, we comprehensively compared retinal autoantigens recognized by sera from BD patients with uveitis or healthy donors using proteomic technique, 2-dimensional electrophoresis (2DE) followed by Western blotting (WB). Six protein spots showing high reactivity with the serum from the BD patients were detected as candidate retinal autoantigens, and three of them were identified by mass spectrometry. Two of them were previously reported BD autoantigens, S-antigen and alpha-enolase, whereas the third one was selenium binding protein (SBP), a new candidate retinal autoantigen. Autoantigenicity of SBP was examined by WB and enzyme-linked immunosorbent assay (ELISA) using a recombinant protein. We found that 20 and 16% of the BD patients with uveitis were positive for the anti-SBP antibody by WB and ELISA, respectively. Comparison of clinical parameters between anti-SBP antibody-positive and -negative patients revealed that the anti-SBP antibody-positive patient group showed more frequent ocular inflammation than the antibody-negative patient group. Autoimmunity against the retinal SBP may contribute to the pathogenesis of uveitis in BD patients. PMID- 17343849 TI - Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus. AB - In rats, the pharmacological (interoceptive) effects of 0.4 mg/kg nicotine can serve as a conditional stimulus in a Pavlovian conditioning task. Nicotine administration is paired with intermittent access to a liquid sucrose unconditional stimulus; sucrose is withheld on saline sessions. An increase in sucrose receptacle entries (goal tracking) on nicotine sessions indicates conditioning. Rats were trained on a nicotine dose ((-)-1-Methyl-2-(3 pyridyl)pyrrolidine; 0.1, 0.2, or 0.4 mg base/kg, s.c.). Generalization was examined using 0.025, 0.05, 0.1, 0.2, and 0.4 mg/kg nicotine and saline. Some behavioral effects of nicotine have been attributed to dopamine and glutamate. Accordingly, potential blockade of the nicotine cue via the dopamine system was examined by administering (R)-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5 tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390; 0.005, 0.01, and 0.03 mg/kg), 3-Chloro-5-ethyl-N-[[(2S)-1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2 methoxy-benzamide hydrochloride (eticlopride; 0.01, 0.03, 0.1, and 0.3 mg/kg), or N-[(1-Butyl-2-pyrrolidinyl)methyl]-4-cyano-1-methoxy-2-naphthalenecarboxamide (nafadotride; 0.03, 0.1, 0.3, 1, and 3 mg/kg) before nicotine. 2-Methyl-6 (phenylethynyl)pyridine hydrochloride (MPEP; 0.3, 1, and 3 mg/kg) and (5S,10R) (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801; 0.01, 0.03, 0.1, and 0.2 mg/kg; dizocilpine) were used to examine possible glutamatergic components. Substitution tests were conducted with MPEP and nafadotride. Differential conditioned responding was acquired in the 3 groups. Conditioned responding generally decreased as the nicotine test dose moved away from the training dose; responding increased when 0.4 mg/kg trained rats were tested with 0.2 mg/kg. SCH-23390, eticlopride, nafadotride, and MPEP decreased conditioned responding on nicotine at doses that also decreased chamber activity. In contrast, MK-801 decreased goal tracking on nicotine without decreasing chamber activity, indicating a role for N-methyl-D-aspartate receptors in expression of nicotine-evoked conditioned responding. PMID- 17343852 TI - Nuclear kinesis, neurite sprouting and abnormal axonal projections of cone photoreceptors in the aged and AMD-afflicted human retina. AB - Tissues often respond to damage by recapitulating developmental programs. We have investigated whether anatomical signs of developmental recapitulation are evident in cone photoreceptors of the aged and AMD-afflicted human retina. Radial migration of cell nuclei mediated by microtubules is a characteristic feature of cells in the developing retina. Similarly, neurite outgrowth is a feature of developing neurons. We have examined whether nuclear kinesis and neurite outgrowth from cone photoreceptors is evident. Calbindin-positive cone photoreceptor nuclei are normally positioned as a single layer of somata at the outer border of the outer nuclear layer. In AMD-afflicted retinae, many nuclei are translocated, with some somata abutting the outer plexiform layer (OPL) and others outside the outer limiting membrane whilst many nuclei are present at intermediate levels. The axonal processes of many cones were also aberrant, displaying tortuous pathways as they projected to the OPL, with occasional evidence for bifurcation at points where the axon changed direction. We suggest that tangential extension of collateral neurites and the rapid retraction of the original process may give rise to the tortuous axonal projections observed. Since microtubules are key mediators of both neurite extension and nuclear kinesis we examined expression of microtubule associated protein 2 (MAP2) which is an important regulator of neurite extension. The strong expression of MAP2 observed in those cells with aberrant morphologies supports the notion that abnormal microtubule-mediated remodelling events are present in the AMD retina and to a lesser extent in normal aged retinas, allowing cone photoreceptors to recapitulate two key features of development. PMID- 17343854 TI - Molecular dynamics simulations of palmitate entry into the hydrophobic pocket of the fatty acid binding protein. AB - The entry of substrate into the active site is the first event in any enzymatic reaction. However, due to the short time interval between the encounter and the formation of the stable complex, the detailed steps are experimentally unobserved. In the present study, we report a molecular dynamics simulation of the encounter between palmitate molecule and the Toad Liver fatty acid binding protein, ending with the formation of a stable complex resemblance in structure of other proteins of this family. The forces operating on the system leading to the formation of the tight complex are discussed. PMID- 17343853 TI - Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway. AB - Fenofibrate, a widely used hypolipidemic drug, has anti-inflammatory and anti atherosclerotic effects in the vessel wall. In the present study, we report an anti-apoptotic property of fenofibrate in human retinal endothelial cells (HRECs) and describe an underlying molecular mechanism. Treatment with fenofibrate protected HRECs from apoptosis in response to serum deprivation in a dose dependent manner. This inhibition of apoptosis by fenofibrate was not altered by peroxisome proliferator-activated receptor alpha (PPARalpha) antagonist MK 886, and selective agonist for PPARalpha, WY-14643 had no beneficial effects on serum deprivation-induced cell death. Fenofibrate potently induced a sustained activation of AMP-activated protein kinase (AMPK) and vascular endothelial growth factor (VEGF) mRNA expression. Furthermore, compound C, a specific AMPK inhibitor, almost completely blocked the fenofibrate-induced survival effect as well as VEGF mRNA expression. Taken together, these results suggest that fenofibrate prevents apoptotic cell death induced by serum deprivation through PPARalpha-independent, but AMPK-dependent pathway. Thus fenofibrate may have a novel therapeutic property that can control unwanted cell death found in diabetic retinopathy. PMID- 17343855 TI - Toward gene therapy of endometriosis: adenovirus-mediated delivery of dominant negative estrogen receptor genes inhibits cell proliferation, reduces cytokine production, and induces apoptosis of endometriotic cells. AB - OBJECTIVE: To use dominant negative mutants of estrogen receptor genes delivered to endometriosis cells via an adenovirus vector (Ad-DN-ER) to abrogate estrogen action on these cells. DESIGN: Experimental in vitro study. SETTING: University research laboratory. PATIENT(S): Patients with ovarian endometriomas provided endometriotic cells, and patients with uterine prolapse or subserous leiomyoma provided control endometrial cells. INTERVENTION(S): Transfection of endometriotic cells by dominant negative estrogen receptor genes via adenovirus vector (Ad-DN-ER). MAIN OUTCOME MEASURE(S): The main outcome measures were cellular proliferation, cytokine production, and induction of apoptosis in endometriotic cells. RESULT(S): Coxsackievirus-adenovirus receptor mRNA expression and adenovirus transduction efficiency were significantly higher in endometriotic than normal endometrial cells. Ad-DN-ER-treated endometriotic cells, as compared with control virus-treated cells, showed cell rounding and detachment (cell death), a 72% reduction in the number of viable cells 5 days after transduction, significantly less production of monocyte chemotactic protein 1 (7.8 +/- 0.5 vs. 152.8 +/- 1.9 pg/mL, respectively), vascular endothelial growth factor (356.2 +/- 11.6 vs. 997.3 +/- 16.5 pg/mL, respectively), and interleukin-6 (268.7 +/- 2.6 vs. 414.5 +/- 3.6 pg/mL, respectively), and a significantly higher percentage of apoptotic cells (51.2 +/- 7.8 vs. 23.8 +/- 1.7, respectively). CONCLUSION(S): An adenovirus can effectively transfect endometriotic cells in vitro. The DN-ER delivered to endometriotic cells via an adenovirus decreases cell proliferation, induces apoptosis, and decreases cytokine production. Adenovirus-mediated gene therapy may represent a potential therapeutic option for endometriosis in the future. PMID- 17343856 TI - Retrograde ejaculation: simpler treatment. AB - OBJECTIVE: To report a case of successful treatment of complete retrograde ejaculation by use of a novel, simple, and noninvasive home-based protocol. DESIGN: Case report. SETTING: Private family medicine clinic. PATIENT(S): A couple with primary infertility due to the male's complete retrograde ejaculation due to childhood's bladder surgery. The woman was healthy with normal menstrual cycles. INTERVENTION(S): After intercourse, the male patient voided a urine-semen mixture from a previously alkalinized urine and proceeded to inseminate it intravaginally into his wife. Determination of best time for intercourse was done by use of the ovulation (Billings) method. RESULT(S): This protocol has been used successfully by this couple to conceive two healthy children. CONCLUSION(S): To our knowledge, this is the second reported case of successful management of infertility through this protocol. It might be appropriate to try this method first on select patients with retrograde ejaculation. PMID- 17343857 TI - Successful pregnancy outcome with the use of in vitro fertilization after Essure hysteroscopic sterilization. AB - OBJECTIVE: To assess the compatibility of pregnancy after IVF and ET procedures with the presence of the Essure microinsert. DESIGN: Prospective, single-arm, clinical study (Canadian Task Force classification III). SETTING: Clinical research center. PATIENT(S): Two women requesting IVF and ET procedures after Essure microinsert sterilization. INTERVENTION(S): Hysteroscopic sterilization, followed by IVF and ET procedures. MAIN OUTCOME MEASURE(S): Successful implantation and pregnancy outcomes after IVF procedures. RESULT(S): Both patients underwent a second-look hysteroscopy within 3 months of an IVF procedure. Device encapsulation by tissue ingrowth reduced the average number of coils trailing into the uterine cavity from four to one, with no evidence of inflammation or any other abnormality. One woman conceived in her second IVF cycle after the transfer of two embryos, and the second woman conceived in her first cycle after the transfer of 1 embryo. Ultrasound showed that the proximal echogenic segments of the microinserts remained > or =10 mm distant from the pregnancy sac. Both women had spontaneous vaginal deliveries of healthy female infants. Postpartum ultrasound demonstrated that the microinserts maintained their prepregnancy utero-tubal locations. CONCLUSION(S): The Essure microinsert used for hysteroscopic sterilization may be compatible with implantation and successful pregnancy outcomes after IVF. PMID- 17343858 TI - Risk of monozygotic twinning with blastocyst transfer decreases over time: an 8 year experience. AB - OBJECTIVE: The purpose of our study is to compare the occurrence of monozygotic twinning (MZT) from blastocyst transfer (BT) in our program between an earlier and more recent time period. DESIGN: Retrospective. SETTING: Academic IVF practice. PATIENT(S): All pregnancies conceived between March 2002 and December 2005 (N = 932) in our program were compared to pregnancies conceived before March 2002 (N = 554), which were the subject of a previous study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The incidence of MZT with day 3 embryo transfer and BT were compared between the study and control groups. RESULT(S): During the study period, the rate of MZT was not significantly different for BT at 2.3% (9/385) compared to day 3 embryo transfer at 1.8% (10/547). This rate of 2.3% for BT was significantly lower than the rate of 5.6% (11/197) reported at our institution for BT before March 2002. CONCLUSION(S): Our study suggests that the risk of MZT with BT is significantly lower in the more recent time period and is in the range of what is seen with cleavage stage transfer. It is likely that improvements in culture systems as experience is gained with BT played a role. PMID- 17343859 TI - Ureteral suspension facilitates surgery for deep pelvic endometriosis. AB - This study describes a technique that facilitates the identification of the ureter during radical excision of endometriosis. After dissection of the ureter, a biocompatible silicone sling is introduced into the pelvis through the trocar; the sling is applied around the ureter and the two ends of the sling are pulled until adequate traction on the ureter is obtained. Ureteral suspension was performed in 126 consecutive women with endometriotic lesions involving the ovarian fossa and/or the uterosacral ligaments. This surgical technique facilitated the identification of the ureter, preventing injuries. PMID- 17343860 TI - Improvement on an inverted decoupling technique for a class of stable linear multivariable processes. AB - This paper improves an inverted decoupling technique for a class of stable linear multivariable processes with multiple time delays and nonminimum-phase zeros. Two decoupling schemes are proposed based on the inverted decoupling technique. One is a developed inverted decoupling scheme. In this scheme, the decoupler is designed such that the inverted decoupling technique accommodates a wider field than the one introduced in the published literature. However, due to the stability issue, some multivariable processes still cannot be decoupled by the inverted decoupling structure. To solve this problem, another modified decoupling scheme with unity feedback structure is suggested for implementation. The Internal Model Control (IMC) theory is applied here to design PI/PID controllers for the decoupled processes. Furthermore, in the presence of multiplicative input uncertainty, low bounds of the control parameters are derived quantitatively for guaranteeing robust stability of the system. Simulations are illustrated for demonstrating the validity of the proposed control schemes. PMID- 17343861 TI - Dyslipidaemia and cardiorenal disease: mechanisms, therapeutic opportunities and clinical trials. AB - Dyslipidaemia is an important risk factor for the development of chronic kidney disease (CKD) and cardiovascular disease (CVD). CKD generates an atherogenic lipid profile, characterised by high triglycerides, low high-density lipoprotein (HDL) cholesterol and accumulation of small dense low-density lipoprotein (LDL) particles, comparable to that in the metabolic syndrome. These changes are due specifically to the effects of CKD on key enzymes, transfer proteins and receptors involved in lipid metabolism. Dyslipidaemia is further compounded by dialysis, immunosuppressive drugs, and concomitant diseases such as diabetes mellitus. Post hoc analyses from large intervention trials suggest the benefit of statins in patients with early CKD, but prospective clinical trials in haemodialysis (HD) and renal transplant recipients have not conclusively shown improvements in hard cardiovascular end-points. The lack of efficacy of statins in late-stage CKD could be a consequence of other disease processes, such as calcific arteriopathy and insulin resistance, which are not modified by lipid lowering agents. Despite uncertainty and pending the results of ongoing statin trials such as Study of Heart and Renal Protection (SHARP) and AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events), major international guidelines continue to support statin therapy in CKD and renal transplant patients to reduce cardiovascular risk burden. Because of increased risk of toxicity, particularly myopathy, statins and other lipid-regulating agents should be used cautiously in CKD and renal transplant recipients. PMID- 17343863 TI - Validation of analytical methods based on accuracy profiles. AB - Validation is a very living field in analytical chemistry as illustrated by the numerous publications addressing this topic. But, there is some ambiguity in this concept and the abundant vocabulary often does not help the analytical chemist. This paper presents a new method based on the fitness-for-purpose approach of the validation. It consists in building a graphical decision-making tool, called the accuracy profile. Using measurements collected under reproducibility or intermediate precision condition, it allows computing an interval where a known proportion of future measurements will be located. When comparing this interval to an acceptability interval defined by the result end-user it is possible to simply decide whether a method is valid or not. The fundamentals of this method are presented starting from an accepted definition of validation. An example of application illustrates how validation can be experimentally organized and conclusion made. PMID- 17343862 TI - Identification of a locus modulating serum C-reactive protein levels on chromosome 5p15. AB - OBJECTIVE: Individual propensity to chronic, low-grade inflammation--a determinant of atherosclerosis-is in part under the control of genetic factors. To identify genes involved in this modulation, we performed a 10cM genome screen for linkage with plasma C-reactive protein in 38 extended families including 317 non-diabetic and 177 type 2 diabetic family members (2547 relative pairs). METHODS AND RESULTS: In a variance component analysis, heritability of CRP values was significant (h(2)=0.39, p<0.0001). This effect was independent of BMI and was present in both diabetic (h(2)=0.42, p=0.003) and non-diabetic (h(2)=0.34, p=0.0015) relatives. The strongest evidence of linkage with CRP was on chromosome 5p15, where the LOD score reached genome-wide significance (LOD=3.41, genome-wide p=0.013). Both diabetic and non-diabetic family members contributed to linkage at this location. Smaller linkage peaks were detected on chromosomes 5q35 (LOD=1.35) and 17p11 (LOD=1.33). When the analysis was restricted to diabetic family members, another peak of moderate intensity (LOD=2.17) was evident at 3p21. CONCLUSIONS: A major gene influencing CRP levels appears to be located on chromosome 5p15, with an effect that is independent of diabetes. Another gene on 3p21 may control CRP variation but only in the presence of a diabetic or insulin resistant environment. PMID- 17343864 TI - Characterization of functionalized styrene-butadiene rubber by flow field-flow fractionation/light scattering in organic solvent. AB - Flow field-flow fractionation (FlFFF) using an organic solvent as mobile phase has been effectively utilized for the separation and characterization of functionalized styrene-butadiene rubbers (SBR) that are polymerized and followed by coupling reaction in solution. Separation of broad molecular weight SBR was accomplished by an asymmetrical FlFFF channel in THF under field programming and the molecular weight distribution (MWD) of the SBR sample was determined by on line measurement of light scattering. In this study, FlFFF has been utilized to characterize high-MW functionalized SBR from the low-MW non-functionalized molecules which were used for coupling reaction to produce high-MW functionalized SBRs, and to determine the coupling number of the functionalized SBRs depending on the type of the coupling reagents. The resulting MWD of the SBR samples prepared by the different coupling reagents (SnCl(4) and a polydimethylsiloxane compound) were compared. PMID- 17343865 TI - Analysis of sulfur compounds from the in-oven roast beef aroma by comprehensive two-dimensional gas chromatography. AB - After a previous investigation of carbonyl compounds in the in-oven top note of roast beef [S. Rochat, A. Chaintreau, J. Agric. Food Chem. 53 (2005) 9578], this paper focuses on the role of sulfur compounds. Because of the complexity of the roast beef headspace where sulfur compounds occur in trace amounts, a high resolution and sensitive technique, comprehensive two-dimensional gas chromatography (GC x GC), was chosen, that allowed the detection of thousands of compounds in the oven headspace. As identifying all of them would be too time consuming, a strategy had to be developed to extract the pertinent information. More than 70 sulfur compounds were found by GC x GC hyphenated to time-of-flight mass spectrometry (TOF-MS), and the identity of 50 of them was confirmed. To overcome the absence of many retention indices in databanks, the missing values were simulated using a multiple linear regression to help the peak identification. The selection of the most important sulfur odorants from this list was achieved by GC-olfactometry, using the GC-"SNIF" technique. Seven compounds have been found for the first time in beef aroma, of which only one has been previously found in nature. PMID- 17343866 TI - Use of a cell model for the evaluation of the dynamic mobility of spherical silica suspensions. AB - In this paper we evaluate the validity of a cell model for the calculation of the dynamic mobility of concentrated suspensions of spheres. The key point is the consideration of the boundary conditions (electrical and hydrodynamic) at the boundary of the fluid cell surrounding a single probe particle. The model proposed is based on a universal criterion for the averages of fluid velocity, electric potential, pressure field or electrochemical properties in the cell. The calculations are checked against a wide set of experimental data on the dynamic mobility of silica suspensions with two different radii, several ionic strengths, and two particle concentrations. The comparison reveals an excellent agreement between theory and experiment, and the model appears to be extremely suitable for correctly predicting the behavior of the dynamic mobility, including the changes in the zeta potential, zeta, with ionic strength, the frequency and amplitude of the Maxwell-Wagner-O'Konski relaxation, and the inertial relaxation occurring at the top of the frequency range accessible to our experimental device. PMID- 17343867 TI - Comparative study for the removal of methylene blue via adsorption and photocatalytic degradation. AB - Physically and chemically activated carbons were prepared from date pits and olive stones. Titania and WO(x)-TiO(2)/MCM-41 were prepared as photoactive catalysts. Surface characterizations were investigated from ash content, pH, base neutralization capacities and FT-IR techniques. The textural characteristics, namely specific surface area (S(BET)) and pore texture, were determined from low temperature adsorption of N(2) at 77 K. The decolorization of aqueous solution of methylene blue was performed by means of two alternative methods. Steam-activated carbons own higher surface area compared with ZnCl(2)-activated carbons, and the micropore surface area represents the major contribution of the total area. Steam activated carbons were the most efficient decolorizing adsorbents owing to its higher surface area, total pore volume and the basic nature of the surface. The calculated values of DeltaG(0), DeltaH(0) and DeltaS(0) indicate the spontaneous behavior of adsorption. The photocatalytic degradation is more convenient method in decolorizing of methylene blue compared with the adsorption process onto activated carbons. PMID- 17343868 TI - Surface treatment and characterization of ITO thin films using atmospheric pressure plasma for organic light emitting diodes. AB - Ar atmospheric pressure plasma (APP) was used to treat indium-tin-oxide (ITO). The plasma conditions were varied to treat the ITO surface, e.g., plasma treatment time, RF power, flow rate, and the plasma outlet-to-sample distance. The plasma effectiveness was measured by the contact angle. The change in the surface energy calculated with the Owens-Wendt method mainly arises from the polar component. The dynamic contact angle measurements show that APP-treated surface showed considerably lower hysteresis in the water and ethylene glycol but there was no change in hysteresis in methylene iodide compared with the untreated ITO. Atomic force microscopy showed that the Ar APP-treated surface sharply decreased the surface roughness and showed a similar morphology as the untreated ITO. X-ray photoelectron spectroscopy showed that the Ar APP treatment not only effectively removed carbon contamination from the surface but also introduced oxygen. Therefore, it is believed that the APP treatment modifies the physico chemical properties of ITO, which can in turn improve the performance of the organic light-emitting diodes. PMID- 17343869 TI - The role of polymer compatibility in the adhesion between surfaces saturated with modified dextrans. AB - Wet and dry adhesion between dextran-coated surfaces were measured aiming to understand the influence of polymer compatibility. The wet adhesion measurements were performed using the atomic force microscope (AFM) colloidal probe technique whereas the dry adhesion measurements were performed using the micro adhesion measurement apparatus (MAMA). Two types of dextrans were used, one cationically modified dextran (DEX) and one that was both cationically and hydrophobically modified (HDEX), leading to three different combinations of polymer-coated surfaces; (1) DEX:DEX, (2) HDEX:DEX, and (3) HDEX:HDEX. DEX increased dry adhesion more than HDEX did, which likely is due to differences in the ability to form specific interactions, especially hydrogen bonding. HDEX gave strong wet adhesion, probably due to its poorer solvency, while DEX contributed to reducing the wet adhesion due to its hydrophilicity. All combinations showed a steric repulsion on approach in aqueous media. Furthermore, when HDEX was adsorbed on either or both surfaces a long range attractive force between the surfaces was detected outside this steric regime. PMID- 17343870 TI - Deformation and motion of a charged conducting drop in a dielectric liquid under a nonuniform electric field. AB - As a tool for transporting a drop inside another fluid, a charged conducting drop driven by Coulombic force is considered. Specifically, deformation and motion of a charged conducting drop under nonuniform electric fields are studied using the perturbation method. For simplicity in analysis, the applied electric field is assumed to be expressed as the sum of a uniform field and a linear field and the flow is assumed to be in the Stokes flow range. The deformed drop shape due to electrical stress is computed to the first order of the electrical Weber number (W). Then the electric force and the hydrodynamic drag are computed to derive the formula of the translation velocity, which is valid up to O(W). Several important results have also been obtained for the effect of drop deformation on the electric and hydrodynamic forces exerted on the drop. PMID- 17343871 TI - Adsorption of phenol and benzyl alcohol onto surfactant modified silica. AB - The adsorption of the surfactant, dodecyltrimethylammonium bromide, DTAB, and the co-adsorption of the additives phenol and benzyl alcohol, onto silica from aqueous solutions are investigated. The adsorption of DTAB is found to increase with increasing alcohol concentration in solutions where the DTAB concentration is below the cmc. Moreover, the corresponding adsorption of DTAB decreases when the DTAB concentration is above the cmc. The co-adsorption of the alcohol is found to increase with increasing alcohol concentration, and benzyl alcohol co adsorbs more strongly than phenol. The surfactant modified silica shows a very high ability to incorporate phenol and benzyl alcohol. The results are discussed in relation to solubilization site and surfactant aggregate shape. PMID- 17343872 TI - School-aged children with SLI: the ICF as a framework for collaborative service delivery. AB - Reports of associated disabilities among children with specific language impairment (SLI) and children with other developmental disabilities are widespread. Clinicians require a broader definition of SLI that recognizes associated disabilities because it is their goal to impact children's everyday functioning. In this paper, we explore SLI from a broader perspective in which consideration is given to features known to be common across different developmental disabilities. The World Health Organization's (2001) International Classification of Functioning, Disability and Health (ICF) is utilized as an organizational and conceptual framework for considering how knowledge of commonalities across developmental disabilities may be used to promote collaborative service delivery in an educational setting. This framework can potentially provide a coherent and comprehensive approach to treating SLI and its associated disabilities without overburdening clinical services. LEARNING OUTCOMES: As a result of this activity, the reader will be able to: (1) describe the potential role of the ICF in facilitating collaborative service delivery in the school setting; (2) identify and describe the commonalities among SLI and its associated disabilities; and (3) describe how knowledge of commonalities may inform approaches to service delivery. PMID- 17343873 TI - Novel microneutralization assay for HCMV using automated data collection and analysis. AB - In addition to being sensitive and specific, an assay for the assessment of neutralizing antibody activity from clinical trial samples must be amenable to automation for use in high-volume screening. To that effect, we developed a 96 well microplate assay for the measurement of HCMV-neutralizing activity in human sera using the HCMV-permissive human cell line HEL-299 and the laboratory strain of HCMV AD169. The degree to which neutralizing antibodies diminish HCMV infection of cells in the assay is determined by quantifying the nuclei of infected cells based on expression of the 72 kDa IE1 viral protein. Nuclear IE1 is visualized using a highly sensitive immunoperoxidase staining and the stained nuclei are counted using an automated ELISPOT analyzer. The use of Half Area 96 well microplates, with wells in which the surface area of the well bottom is half the area of a standard 96-well microplate plate, improves signal detection compared with standard microplates and economizes on the usage of indicator cells, virus, and reagents. The staining process was also streamlined by using a microplate washer and data analysis was simplified and accelerated by employing a software program that automatically plots neutralization curves and determines NT(50) values using 4-PL curve fitting. The optimized assay is not only fast and convenient, but also specific, sensitive, precise and reproducible and thus has the characteristics necessary for use in measuring HCMV-neutralizing activity in the sera of vaccine trial subjects such as the recipients of Vical's HCMV pDNA vaccine candidates. PMID- 17343874 TI - Generation and sustained expansion of mouse spleen invariant NKT cell lines with preserved cytokine releasing capacity. AB - Invariant Natural Killer T (iNKT) cells are CD1d restricted innate lymphoid cells with an invariant T cell receptor (TCR) alpha chain gene rearrangement (Valpha24 Jalpha18 in human and Valpha14-Jalpha18 in mouse). iNKT cells play a pivotal role in anti-tumor immune responses via cytokine mediated transactivation of various cells which mediate innate and adaptive immune responses. Here we describe, to our knowledge for the first time, the generation of long-term mouse spleen derived iNKT cell lines. We found that dendritic cells (DC) derived from the D1 line, but not Mf4/4 macrophages, loaded with the artificial iNKT cell ligand alpha-Galactosylceramide (alphaGalCer) could be employed to expand iNKT cells in vitro. Furthermore, exogenously added IL-7, but not IL-2 or IL-15 had a pronounced additive effect on iNKT cell expansion. Using this method up to 10(8) iNKT cells could be obtained from one spleen within 12 to 14 weeks, and cell lines could be continued for up to 24 months. Importantly, the iNKT cell lines had retained the capacity to swiftly secrete substantial amounts of both T helper (Th) 1 and Th2 cytokines upon activation. In conclusion we have generated iNKT cell lines with high yields that can be maintained for up to 24 months, by repeated stimulation using alpha-GalCer loaded D1.DC and IL-7. These in vitro expanded iNKT cells preserved the capacity to swiftly produce both Th1 and Th2 type cytokines and are currently being utilized in pre-clinical adoptive transfer models to identify and optimize the characteristics of therapeutically effective iNKT cells in an anti-tumor setting. PMID- 17343875 TI - Gene expression signals involved in ischemic injury, extracellular matrix composition and fibrosis defined by global mRNA profiling of the human left ventricular myocardium. AB - Gene expression signals involved in ischemic injury, extracellular matrix composition and fibrosis defined by global mRNA profiling of the human left ventricular myocardium. The mechanism(s) by which acute and chronic myocardial ischemia translate into the characteristic features of ischemic cardiomyopathy is unresolved at present. We hypothesized that such translation relates to modification of specific gene expression programs during acute and chronic ischemic insults to the myocardium. Global mRNA expression profiles by Affymetrix HG_U133A GeneChip analysis on 33 samples was performed on non-failing human left ventricular myocardium during acute and chronic ischemia in 6 patients undergoing coronary artery by-pass grafting. Results were confirmed by real-time quantitative RT-PCR in 14 patients and supported by histology and immunohistochemistry analyses. Acute ischemia elicited an acute inflammatory response including IL-6, IL-8, MCP-1, VCAM-1 and CYR-61 with an attenuated increase of IL-6 and IL-8 in chronic ischemic myocardium compared to normal myocardium. High mRNA expression of connective tissue growth factor (CTGF) was present in chronic ischemic myocardium with a high degree of correlation between CTGF and mRNA expression of specific genes (e.g. thrombospondin 4, collagen type Ialpha2, versican, adlican, latent transforming growth factor beta binding protein 2 and fibronectin) involved in extracellular matrix remodelling. In conclusion, acute inflammatory induction (e.g. IL-8, IL-6, VCAM-1 and MCP-1) and an acute phase CCN family gene with effects on matrix interactions (CYR-61) might play important roles in the coupling between acute ischemic episodes and chronic myocardial remodelling. In addition, the findings support an important role of CTGF signalling in chronic extracellular matrix remodelling in chronic coronary artery disease. PMID- 17343876 TI - Dynamical properties of autoimmune disease models: tolerance, flare-up, dormancy. AB - The mechanisms of autoimmune disease have remained puzzling for a long time. Here we construct a simple mathematical model for autoimmune disease based on the personal immune response function and the target cell growth function. We show that these two functions are sufficient to capture the essence of autoimmune disease and can explain characteristic symptom phases such as tolerance, repeated flare-ups and dormancy. Our results strongly suggest that a more complete understanding of these two functions will underlie the development of an effective therapy for autoimmune disease. PMID- 17343877 TI - Microarray analysis reveals influence of the sesquiterpene lactone parthenolide on gene transcription profiles in human epithelial cells. AB - Sesquiterpene lactones are known for their anti-inflammatory activity which has been proven in various assays on DNA, mRNA and protein level. Here we report on the change in the gene expression profile in TNF-alpha stimulated human 293 cells after treatment with parthenolide using a cDNA microarray analysis. Twenty-one of 7028 genes were found to be up- and 18 down-regulated. They encode for chemoattractants, immune system proteins, glycoproteins, metabolism, serine proteinases, and transcription factors. Confirmatory analyses were carried out using quantitative real-time RT-PCR (TaqMan). Additional studies with selected genes revealed the concentration-dependent influence of parthenolide on the expression of these genes. PMID- 17343879 TI - Retinal arteriolar hemodynamic response to an acute hyperglycemic provocation in early and sight-threatening diabetic retinopathy. AB - The aim was to quantify the magnitude of retinal arteriolar vascular reactivity to a hyperglycemic provocation in diabetic patients stratified by severity of retinopathy and in age-matched controls. The sample comprised 20 non-diabetic controls (Group 1), 19 patients with no clinically visible DR (Group 2), 18 patients with mild-to-moderate non-proliferative DR (Group 3) and 18 patients with diabetic macular edema (Group 4). Retinal hemodynamic measurements using the Canon Laser Blood Flowmeter (CLBF-100) were acquired before and 1 h after drinking a standardized oral glucose load drink. The magnitude of the retinal vascular response, as well as max:min velocity ratio and wall shear rate (WSR), was calculated and compared across groups. A significant change in blood glucose level was observed for all groups (p<0.05). The change in blood glucose elevation was significantly less in Group 1 compared to the other groups. No significant change in arteriolar diameter, blood velocity, blood flow, max:min velocity ratio and WSR was found in patients with diabetes and in age-matched subjects without diabetes. The results of this study indicate that retinal arteriolar blood flow is unaffected by acute elevation of blood glucose using an oral glucose load drink in patients with diabetes and in age-matched controls. This lack of a blood flow response to acute hyperglycemia in patients with early sight-threatening DR may be explained by a loss of retinal vascular reactivity. PMID- 17343880 TI - Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure. AB - Micro RNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. They play a crucial role in the regulation of genes involved in the control of development, cell proliferation, apoptosis, and stress response. Although miRNA levels are substantially altered in tumors, their role in carcinogenesis, specifically at the early pre-cancerous stages, has not been established. Here we report that exposure of Fisher 344 rats to tamoxifen, a potent hepatocarcinogen in rats, for 24 weeks leads to substantial changes in the expression of miRNA genes in the liver. We noted a significant up-regulation of known oncogenic miRNAs, such as the 17-92 cluster, miR-106a, and miR-34. Furthermore, we confirmed the corresponding changes in the expression of proteins targeted by these miRNAs, which include important cell cycle regulators, chromatin modifiers, and expression regulators implicated in carcinogenesis. All these miRNA changes correspond to previously reported alterations in full-fledged tumors, including hepatocellular carcinomas. Thus, our findings indicate that miRNA changes occur prior to tumor formation and are not merely a consequence of a transformed state. PMID- 17343882 TI - Characteristics of ejaculated rat semen after lesion of scrotal nerves. AB - The scrotum, representing the pouch surrounding the testes and their associated structures, plays a significant role in maintaining the gonad at a temperature lower than that of the body. Although thermoregulation of the testes has been ascribed as a main function of the scrotum, here we found that mechanical stimulation of the scrotum is important during mating to facilitate the appropriate expulsion of semen during ejaculation. Previously we showed that the scrotal skin area is innervated by two nerve branches, the proximal (Psb) and distal (Dsb) scrotal branches which supply the proximal or distal half of the scrotum, respectively. The sensory field of each nerve is testosterone-dependent. The decreased androgen levels following castration reduce the sensitive area to mechanical stimuli that can be restored following exogenous administration of the hormone. Here, we tested the effect of scrotal nerve transection on sexual parameters of experienced male rats. Data show that lesion of PSb or DSb alone or combined did not affect the execution of sexual behavior. However, these lesions significantly reduced the proportion of males that expelled semen during ejaculation, with that semen showing a reduced quantity of sperm. Thus, scrotal nerves are important in reproduction not for the appropriate display of sexual behavior, but for the expulsion of a normal quantity of semen and number of sperm during ejaculation. Our suggestion is that scrotal afferents trigger spinal reflexes to activate autonomic efferents supplying the male reproductive tract for the control of seminal emission. PMID- 17343883 TI - Memory enhancing activity of Anwala churna (Emblica officinalis Gaertn.): an Ayurvedic preparation. AB - Ayurveda means "the science of life". Ayur means "life" and Veda means "knowledge or science". It is the oldest medical system in the world. Its origins can be traced as far back as 4500 BC, to four ancient books of knowledge, (the "Vedas") and it is still officially recognized by the government of India. The present study was aimed at investigating the effects of Anwala churna (Emblica officinalis Gaertn.), an Ayurvedic preparation on memory, total serum cholesterol levels and brain cholinesterase activity in mice. Anwala churna was administered orally in three doses (50, 100 and 200 mg/kg) for fifteen days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. Total serum cholesterol levels and brain cholinesterase activity also estimated. Anwala churna (50, 100 and 200 mg/kg, p.o.) produced a dose-dependent improvement in memory scores of young and aged mice. Furthermore, it reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Interestingly, brain cholinesterase activity and total cholesterol levels were reduced by Anwala churna administered orally for 15 days. Anwala churna may prove to be a useful remedy for the management of Alzheimer's disease on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity. PMID- 17343884 TI - Capsaicin treatment differentially affects feeding suppression by bombesin-like peptides. AB - Peripheral administration of bombesin (BN) and the related mammalian peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), suppress food intake in rats. To examine whether all BN-like peptides utilize the same neural pathways to reduce feeding, rats were treated on postnatal day 2 with the injection vehicle or capsaicin, a neurotoxin that damages a subset of visceral afferent fibers. When rats reached adulthood, we compared the ability of a dose range of systemically administered BN, GRP18-27 and NMB to reduce intake of a 0.5 kcal/ml glucose solution in a short-term feeding test. Our results demonstrate that capsaicin treatment abolished or attenuated the suppression of glucose intake produced by BN and NMB but had no effect on the ability of GRP to reduce feeding. These results suggest that different neural substrates underlie the anorexic effects of peripherally administered BN-like peptides. PMID- 17343885 TI - Chemistry and pharmacology of oxyprenylated secondary plant metabolites. AB - Oxyprenylated natural products (isopentenyloxy-, geranyloxy- and the less spread farnesyloxy- compounds and their biosynthetic derivatives) represent a family of secondary metabolites that have been considered for years just as biosynthetic intermediates of C-prenylated derivatives. Only in the last decade these natural products have been recognized as interesting and valuable biologically active phytochemicals. Up to now about 300 molecules have been isolated from plants mainly belonging to the families of Rutaceae and Compositae, comprising common edible vegetables and fruits. A wide variety of compounds containing a prenyloxy side chain have been isolated and these comprise alkaloids, coumarins, flavonoids, cinnamic acids, benzoic acids, phenols, alcohols, aldehydes, anthraquinones, chalcones, lignans, xanthones, aceto- and benzophenones and other more uncommon skeletons. Many of the isolated oxyprenylated natural products and their semisynthetic derivatives were shown to exert in vitro and in vivo remarkable anti-cancer, anti-inflammatory, anti-microbial and anti-fungal effects. The aim of this review is to examine in detail the different types of oxyprenylated natural compounds from a phytochemical and pharmacological point of view. PMID- 17343886 TI - Secondary metabolites from Commiphora opobalsamum and their antiproliferative effect on human prostate cancer cells. AB - A cycloartane-type triterpenoid (1), an aliphatic alcohol glycoside (2), an eudesmane-type sesquiterpenoid (3), and a guaiane-type sesquiterpenoid (4) were isolated from the resinous exudates of Commiphora opobalsamum along with six known sesquiterpenoids (5-10). Their structures were established by extensive analysis of their 1D and 2D NMR spectroscopic data and chemical methods. The isolated compounds 1-3 and 5-9 were tested against human prostate cancer cell PC 3 and LNCaP. Among them, 1 and 2 showed moderate antiproliferative effects on human prostate cancer cell lines with IC50 values ranging from 5.7 to 23.6 microM; they were also able to inhibit the expression of androgen receptor (AR) in LNCaP cells. The six sesquiterpenoids were inactive in the bioassays. PMID- 17343887 TI - The effects of 10% hypertonic saline, 0.9% saline and hydroxy ethyl starch infusions on hydro-electrolyte status and adrenal function in healthy conscious dogs. AB - The purpose of this study was to investigate the influence of different saline and colloid solutions on adrenal steroid secretion in dogs. Six healthy male Beagles underwent three infusion cycles: 10 min infusion of 30 ml/kg of NaCl 0.9%, 5 ml/kg of hydroxy ethyl starch, or 5 ml/kg of NaCl 10%. Plasma osmolality, hematocrit, total solids, cortisol and aldosterone levels were measured at 0, 5, 15, 30, 60, 120, 180 and 240 min after beginning infusion. Plasma ACTH levels were measured at 0, 15 and 240 min. An identical timing of sampling was applied during a control session omitting the fluid infusion. Osmolality, sodium, chloride and cortisol levels were found to be significantly higher with hypertonic saline solute compared to control. All fluid infusions lead to lowered plasma potassium, hematocrit, total solids and aldosterone values. ACTH concentrations did not show significant changes with any of the infusion cycles. The increase in cortisol levels suggests that hypertonic saline infusion could be interesting in critical care resuscitation, particularly in patients who are suffering from relative adrenal insufficiency. PMID- 17343888 TI - Pharmacokinetics after intravenous, intramuscular and subcutaneous administration of difloxacin in sheep. AB - The disposition kinetics of difloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration were determined in sheep at a single dose of 5mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental pharmacokinetics method (after IV, IM and SC administration). Plasma concentrations of difloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (V(ss)) and clearance (Cl) of difloxacin after IV administration were 1.68+/-0.21L/kg and 0.21+/-0.03L/hkg, respectively. Following IM and SC administration difloxacin achieved maximum plasma concentration of 1.89+/-0.55 and 1.39+/-0.14mg/L at 2.42+/-1.28 and 5.33+/ 1.03h, respectively. The absolute bioavailabilities after IM and SC routes were 99.92+/-26.50 and 82.35+/-25.65%, respectively. Based on these kinetic parameters, difloxacin is likely to be effective in sheep. PMID- 17343889 TI - Complex determinants within the Moloney murine leukemia virus capsid modulate susceptibility of the virus to Fv1 and Ref1-mediated restriction. AB - Two of the most well-known genetic mechanisms in mammalian cells which control the susceptibility of cells to productive infection by retroviruses and lentiviruses rely on the cellular Fv1 and Ref1 restriction factors, which act, after viral entry, to prevent productive infection through their interactions with viral capsid (CA) sequences. While previous studies of Fv1 restriction involving N- and B-tropic murine leukemia viruses (MLVs) had demonstrated that the identity of a single amino acid residue at CA110 (arginine vs. glutamic acid) determines whether the resulting virus is N (arg) or B-tropic (glu), analogous studies of dual-tropic MLVs, such as Moloney MLV (Mo-MLV), have shown that additional residues other than CA110 are also involved in the specification of dual-tropic host range. Here we have further studied the CA determinants of Mo MLV host range, with an emphasis on identifying additional CA residues and unique combinations of CA residues which differentially influence the ability of the resulting virus to infect murine and human cells. First, we show that CA82, a residue previously identified to affect the pattern of Fv1 restriction of different MLV viruses in murine cells, is a particularly strong potentiator of B tropism in an Mo-MLV background carrying a glutamic acid residue at CA110 (A110E substitution), and that interestingly, different residues at CA82 lead to distinct patterns of restriction in human but not in murine cells. We also identify another CA residue, CA214, as a similarly potent potentiator of B tropism, in the context of the A110E substitution. While another substitution at CA110, A110R, leads to strong potentiation of N-tropism in murine cells, in the absence of additional mutations, we found that A110R alone was not sufficient to confer appreciable restriction in Ref1-expressing cells, despite the fact that authentic N-MLV shows strong restriction in those cells. In conjunction with the A110R substitution, substitutions at CA82, but not at CA214, do lead to significant restriction in human cells, thus demonstrating a distinction between the interactions between those two determinants of restriction and CA110. Finally, using cell lines engineered to express the TRIM5alpha(hu) gene product, recently identified as the Ref1 restriction factor, and RNAi technology to knock down expression of TRIM5alpha(hu) in human cells, we directly demonstrate that the unique patterns of restriction observed in human cells with the different mutants are consistent with a TRIM5alpha(hu)-mediated restriction. These studies shed further light on the complex determinants within the viral CA gene product which control the susceptibility of murine and human cells to retroviral infection. PMID- 17343890 TI - S-cone contributions to linear and non-linear motion processing. AB - We investigated the characteristics of mechanisms mediating motion discrimination of S-cone isolating stimuli and found a double dissociation between the effects of luminance noise, which masks linear but not non-linear motion, and chromatic noise, which masks non-linear but not linear motion. We conclude that S-cones contribute to motion via two different pathways: a non-linear motion mechanism via a chromatic pathway and a linear motion mechanism via a luminance pathway. Additionally, motion discrimination and detection thresholds for drifting, S-cone isolating Gabors are unaffected by luminance noise, indicating that grating motion is mediated via chromatic mechanisms and based on higher-order motion processing. PMID- 17343891 TI - Colour-luminance interactions in binocular summation. AB - Using a noise-masking paradigm we test the notion of binocular detection mechanisms that combine luminance and colour contrast. Binocular summation was measured for achromatic and red-green isoluminant Gabor stimuli over a range of temporal frequencies and was compared with and without the presence of a two dimensional, dynamic, luminance noise mask (correlated). While we found that luminance noise reduced binocular luminance summation at all temporal frequencies, binocular red-green summation was reduced only at frequencies of 8 Hz and above. Our results suggest the existence of binocular colour-luminance interactions restricted to high temporal frequencies. PMID- 17343892 TI - The economic impact of restricted water supply: a computable general equilibrium analysis. AB - Water problems are typically studied at the level of the river catchment. About 70% of all water is used for agriculture, and agricultural products are traded internationally. A full understanding of water use is impossible without understanding the international market for food and related products, such as textiles. The water embedded in commodities is called virtual water. Based on a general equilibrium model, we offer a method for investigating the role of water resources and water scarcity in the context of international trade. We run five alternative scenarios, analyzing the effects of water scarcity due to reduced availability of groundwater. This can be a consequence of physical constraints, and of policies curbing water demand. Four scenarios are based on a "market solution", where water owners can capitalize their water rent or taxes are recycled. In the fifth "non-market" scenario, this is not the case; supply restrictions imply productivity losses. Restrictions in water supply would shift trade patterns of agriculture and virtual water. These shifts are larger if the restriction is larger, and if the use of water in production is more rigid. Welfare losses are substantially larger in the non-market situation. Water constrained agricultural producers lose, but unconstrained agricultural produces gain; industry gains as well. As a result, there are regional winners and losers from water supply constraints. Because of the current distortions of agricultural markets, water supply constraints could improve allocative efficiency; this welfare gain may more than offset the welfare losses due to the resource constraint. PMID- 17343893 TI - Rapid and direct estimation of active biomass on granular activated carbon through adenosine tri-phosphate (ATP) determination. AB - Granular activated carbon (GAC) filtration is used during drinking water treatment for the removal of micropollutants such as taste and odour compounds, halogenated hydrocarbons, pesticides and pharmaceuticals. In addition, the active microbial biomass established on GAC is responsible for the removal of biodegradable dissolved organic carbon compounds present in water or formed during oxidation (e.g., ozonation and chlorination) processes. In order to conduct correct kinetic evaluations of DOC removal during drinking water treatment, and to assess the state and performance of full-scale GAC filter installations, an accurate and sensitive method for active biomass determination on GAC is required. We have developed a straight-forward method based on direct measurement of the total adenosine tri-phosphate (ATP) content of a GAC sample and other support media. In this method, we have combined flow-cytometric absolute cell counting and ATP analysis to derive case-specific ATP/cell conversion values. In this study, we present the detailed standardisation of the ATP method. An uncertainty assessment has shown that heterogeneous colonisation of the GAC particles makes the largest contribution to the combined standard uncertainty of the method. The method was applied for the investigation of biofilm formation during the start-up period of a GAC pilot-scale plant treating Lake Zurich water. A rapid increase in the biomass of up to 1.1 x 10(10)cells/g GAC dry weight (DW) within the first 33 days was observed, followed by a slight decrease to an average steady-state concentration of 7.9 x 10(9)cells/g GAC DW. It was shown that the method can be used to determine the biomass attached to the GAC for both stable and developing biofilms. PMID- 17343894 TI - Performance of single chamber biocatalyzed electrolysis with different types of ion exchange membranes. AB - In this paper hydrogen production through biocatalyzed electrolysis was studied for the first time in a single chamber configuration. Single chamber biocatalyzed electrolysis was tested in two configurations: (i) with a cation exchange membrane (CEM) and (ii) with an anion exchange membrane (AEM). Both configurations performed comparably and produced over 0.3 m3 H2/m3 reactor liquid volume/day at 1.0 V applied voltage (overall hydrogen efficiencies around 23%). Analysis of the water that permeated through the membrane revealed that a large part of potential losses in the system were associated with a pH gradient across the membrane (CEM DeltapH=6.4; AEM DeltapH=4.4). These pH gradient associated potential losses were lower in the AEM configuration (CEM 0.38 V; AEM 0.26 V) as a result of its alternative ion transport properties. This benefit of the AEM, however, was counteracted by the higher cathode overpotentials occurring in the AEM configuration (CEM 0.12 V at 2.39 A/m2; AEM 0.27 V at 2.15 A/m2) as a result of a less effective electroless plating method for the AEM membrane electrode assembly (MEA). PMID- 17343895 TI - Henry's law constants of phenol and mononitrophenols in water and aqueous sulfuric acid. AB - Phenols are widely present in the atmosphere and nitration probably in the aerosol phase leads to nitrophenols. Nitration by nitric acid in sulfuric acid can be rapid, but little is known of the process under atmospheric conditions. The Henry's law constants K(H)(dagger) of phenol and 2-, 3- and 4-nitrophenol were all measured by a bubble stripping method as: 2820mol kg(-1) atm(-1) (at 298K), 147mol kg(-1) atm(-1) (at 298K), 1.6x10(4)mol kg(-1)atm(-1) (at 308K) and 2.1x10(4)mol kg(-1) atm(-1) (at 308K), respectively. The Henry's law constant of phenol in sulfuric acid systems is lower by more than a factor of two at 1020mol kg(-1) atm(-1) (at 298K) in 40wt% sulfuric acid, which is in line with salting out of oxygen-containing aromatic compounds in water-sulfuric acid systems. The Henry's law constants of 2- and 4-nitrophenol behave differently and are almost independent of sulfuric acid concentration. The variation of K(H)(dagger) with temperature (T) described in terms of -dln(K(H)(dagger))/d(1/T) does not to vary with sulfuric acid concentration, suggesting enthalpy of dissolution for phenol is independent of sulfuric acid. The series of Henry's law constants measured here can describe the equilibrium situation for phenols in careful determinations of phase partitioning in the atmosphere. PMID- 17343896 TI - Effect of physical forms of soil organic matter on phenanthrene sorption. AB - The sorption coefficient, K(OC), of phenanthrene (PHE) has been reported to vary with different types of organic matter, leading to uncertainties in predicting the environmental behavior of PHE. Among the studies that relate organic matter properties to their sorption characteristics, physical conformation of organic matter is often neglected. In this work, organic matter samples of different physical forms were examined for their sorption characteristics. Dissolved humic acids (DHA) showed significantly higher K(OC) than the corresponding solid humic acids (SHA) from which the DHAs were made. The K(OC) of DHAs was found to be related to polarity, whereas K(OC) of SHAs increased with aliphatic carbon content. Soil particles were treated with H(2)O(2) to remove organic matter, and humic acid was coated on H(2)O(2)-treated soil particles to make organo-mineral complexes at pH 4, 7 and 10. Although the nonlinear sorption was apparent for SHAs and H(2)O(2)-treated soil particles, the organo-mineral complexes formed using these two components at pH 4, 7 and 10 exhibited relatively linear sorption at organic carbon content, f(OC)>0.5%. These results indicate that organic matter of the same composition may have different sorption properties due to different physical forms (or conformations). Nonlinear sorption for the complexes formed at pH 4 with lower f(OC) (<0.5%) was also discussed. PMID- 17343897 TI - Radioactivity levels in aerosol particles surrounding a large TENORM waste repository after application of preliminary restoration work. AB - In this paper, (238)U-series radionuclides have been analysed in particulate matter samples collected at a phosphogypsum stack system located near the city of Huelva (SW Spain) during the course of 1 year. The results have been compared to those collected at a reference (background) site located a few km away, in order to establish if the stack system provokes an increase in radionuclide exposure due to inhalation with particulate matter. The (222)Rn progeny, which is considered a very important contributor to the internal dose rate received by the population, was collected for 6 months. The results indicate that for several types of radionuclides there is a significant increase in the radioactivity adsorbed by the aerosol particles collected at phosphogypsum stacks. The isotope analysis indicates that this increment could be affected by the water vapour emissions from the factory, which contain high concentrations of these radionuclides. However, the majority of these radionuclides could not be detected at the background location. The corresponding dose increment estimated at the sampling point is, however, negligible. This fact is a consequence of the very small radionuclide concentration increment, together with relatively conservative nature of the occupational factor applied. Regarding the Rn progeny, no significant differences between either the collecting sites has been registered due to of the dominant wind regime at the sampling locations. PMID- 17343898 TI - Urban and rural exposure to indoor air pollution from domestic biomass and coal burning across China. AB - Although indoor air pollution (IAP) from solid fuel use in the households of the developing countries is estimated to be one of the main health risks worldwide, there is little knowledge of the actual exposure experienced by large populations. We have developed a method to estimate exposure to PM(10) from IAP for large populations, applied to different demographic groups in China. On a national basis we find that 80%-90% of exposure in the rural population results from IAP. For the urban population the contribution is somewhat lower, about 50% 60%. Average exposure is estimated at 340 microg/m(3) (SD 55) in southern cities, and 440 microg/m(3) (SD 40) in northern cities. For the rural population we find average exposure to be 750 microg/m(3) (SD 100) and 680 microg/m(3) (SD 65) in the south and north respectively. Quite surprisingly our results indicate that the heavily polluted northern provinces, largely dependent on coal and believed to have the population with the largest exposure burden, turn out to have medium exposure when IAP is included. We find that the largest exposure burden is in counties relying heavily on biomass, and that there are only small gender differences in exposure. PMID- 17343899 TI - Effects of environmental stress on the condition of Littorina littorea along the Scheldt estuary (The Netherlands). AB - The condition of the periwinkle Littorina littorea, expressed in terms of its shell morphology, reproductive impairment (i.e. female sterility/intersex, male penis shedding), trematode infestation load, lipid reserves and dry/wet weight ratio, was determined in function of environmental stress along the polluted Western and relatively clean Eastern Scheldt estuary (The Netherlands). The upstream increasing pollution and decreasing salinity levels along the Western Scheldt estuary (Fig. 1) are reflected in the dry/wet weight ratio and lipid content of the periwinkles. Compared to the Eastern Scheldt, female intersex (i.e. indicator of TBT pollution) and sterility occurred more frequently in the Western Scheldt estuary, while male penis shedding was even restricted to the latter estuary. The highest population intersex and sterility incidence was found near the harbour of Vlissingen and reflects potential nautical activities. The number of trematode infested periwinkles did not differ between both estuaries, although local sampling site differences were detected within each estuary, reflecting the complex interactions that exist among parasites, hosts and the local environment. Finally, both estuaries were maximally discriminated from each other based on the shell weight of the periwinkles using a canonical discriminant analysis. Periwinkles with the heaviest shells were found in the Western Scheldt estuary and may reflect growth rate or structural population differences caused by the less favourable living conditions in the Western Scheldt estuary. PMID- 17343900 TI - The effects of angiotensin II and genetic hypertension upon extracellular nucleotide hydrolysis by rat platelet ectoenzymes. AB - The extracellular nucleotides, ATP and ADP, as well as adenosine have been implicated in a great number of physiological functions. ADP is one of the major platelet recruiting factors, whereas ATP is considered to be a competitive inhibitor of ADP-induced platelet aggregation and adenosine is able to induce vasodilatation and to inhibit platelet aggregation. The di- and triphosphate nucleosides can be hydrolyzed by members of several families of ectonucleotidases, including ecto-nucleoside triphosphate diphosphohydrolases (E NTPDases) and ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPPs) that, together with an ecto-5'-nucleotidase, catalyze adenosine formation. The renin angiotensin system is the most important regulator of renal and cardiovascular functions and angiotensin II induces, physiologically, platelet activation. The aim of this study was to clarify the effects of ANGII and genetic hypertension upon extracellular nucleotide hydrolysis by rat platelet ectoenzymes. ANGII, in all tested doses (5, 50, 500 and 5000 pmol), was able to increase ATP (21, 31, 44 and 27%, respectively), ADP (22, 28, 78 and 37%, respectively) and AMP (40, 64, 60 and 64%, respectively) hydrolysis by rat platelets. Furthermore, losartan, a specific antagonist of the AT1 angiotensin-receptor, prevented the nucleotide hydrolysis effects. Additionally, an increase in AMP (about 144%) hydrolysis and a decrease in p-Nph-5'TMP (about 27%) hydrolysis were observed in platelets from spontaneously hypertensive rats (SHR) when compared to Wistar normotensive rats. We, herein, present data to demonstrate interactions between rat platelet angiotensinergic and adenosinergic systems that could contribute to the understanding and treatment of cardiovascular diseases such as hypertension, thrombosis and arteriosclerosis. PMID- 17343901 TI - Stimulation of PI 3-kinase signaling via inhibition of the tumor suppressor phosphatase, PTEN. PMID- 17343902 TI - Chemotherapeutic agents and gene expression in cardiac myocytes. PMID- 17343904 TI - Expression of beta-tubulin isotypes in human primary ovarian carcinoma. AB - OBJECTIVE: Selective expression of beta-tubulin isotypes has been reported to be one of the important mechanisms of taxane resistance. The purpose of this study was to evaluate the immunohistochemical expression of beta-tubulin isotypes using clinical samples of ovarian carcinoma treated by taxanes and to examine whether the protein levels of each of the beta-tubulin isotypes were correlated with the clinical features. EXPERIMENTAL DESIGN: We examined tumor samples taken from 77 ovarian carcinoma patients (54 patients treated with a taxane-based regimen and 23 treated with a taxane-free regimen), for the intrinsic protein level of beta tubulin isotype (classes I, II, III and IV) expression using immunohistochemistry, and we evaluated the correlation of this protein level with the clinical features. The expression levels were scored by the proportion and intensity of the immunoreactive tumor cells. RESULTS: High protein levels of classes I and IV beta-tubulin, and very low protein levels of class II beta tubulin, and intermediate protein levels of class III beta-tubulin expression were demonstrated in a total of 77 ovarian carcinomas. As for the samples taken from the 54 patients treated with the taxane-based regimen, 40 samples demonstrated undetectable levels of class II beta-tubulin protein. The class II beta-tubulin expression-absent group was significantly correlated with advanced stage (p=0.024) and with a short period of progression-free survival (log-rank test, p=0.022). Multivariate analyses demonstrated that the only significant independent prognostic indicator of a short period of progression-free survival was advanced stage, although a high expression of class III beta-tubulin was also prone to be associated with a short period of progression-free survival, but not significantly so (p=0.081). No such correlations or propensities were demonstrated in the 23 patients treated with the taxane-free regimen. CONCLUSIONS: In cases of ovarian carcinoma treated by taxanes, high expression of class III beta-tubulin seems to be associated with earlier recurrence, which is believed likely to be resistant relapse. In addition, loss of class II beta tubulin expression is correlated with advanced stage, which may represent aggressive tumor progression. PMID- 17343903 TI - Overexpression of mammaglobin B in epithelial ovarian carcinomas. AB - OBJECTIVE: Mammaglobin B is a uteroglobin gene family member recently found highly differentially expressed in serous papillary ovarian cancer by gene expression profiling. In order to evaluate its potential as a novel ovarian cancer biomarker, in this study we quantified and compared Mammaglobin B expression in various histologic types of epithelial ovarian carcinomas (EOC). METHODS: Mammaglobin B expression was evaluated by real-time PCR and/or immunohistochemistry in fresh-frozen biopsies and paraffin-embedded tissues derived from a total of 137 patients including 69 primary EOC with different histologies, 28 serous papillary omental metastasis, 8 borderline tumors, 26 benign cystadenomas and 14 normal ovaries. RESULTS: High levels of Mammaglobin B gene expression were detected in 100% (68 out of 68) of the ovarian cancer biopsies tested by real-time PCR. In contrast, normal human ovarian surface epithelium (HOSE) expressed negligible levels of Mammaglobin B mRNA (EOC versus HOSE, p<0.01). Although Mammaglobin B gene expression levels were higher in endometrioid, mucinous and undifferentiated tumors when compared to serous papillary tumors, clear cell tumors and those with mixed histology, these differences were not statistically significant. In agreement with real-time PCR results, EOC were found to express significantly higher levels of Mammaglobin B protein when compared to normal ovaries and benign cystadenomas (p<0.01). However, only 29 out of 68 (42%) of the EOC samples found positive for Mammaglobin B by real-time PCR showed immunoreactivity by IHC. CONCLUSIONS: Mammaglobin B gene is highly expressed in EOC and may represent a novel molecular marker for multiple histological types of ovarian cancer. Additional studies to evaluate the clinical utility of Mammaglobin B as a diagnostic and/or therapeutic target in ovarian cancer are warranted. PMID- 17343905 TI - Morphine-3-glucuronide inhibits morphine induced, but enhances morphine-6 glucuronide induced locomotor activity in mice. AB - The main metabolite of morphine, morphine-3-glucuronide (M3G) has no opioid effects. Some studies have rather indicated that it antagonizes the antinociceptive and respiratory depressive effects of both morphine and the active metabolite morphine-6-glucuronide (M6G). We studied the possible influence of M3G on the psychostimulant properties of morphine and M6G measured by locomotor activity. Mice were given two injections, one with either 80, 240 or 500 micromol/kg M3G or saline followed by an injection of 20 or 30 micromol/kg morphine or M6G. M3G influenced the locomotor activity induced by both morphine and M6G, but in opposite directions. M3G reduced the morphine induced locomotor activity during the first hour following morphine injection in a concentration dependent manner. M3G pretreatment did not significantly influence brain concentrations of morphine indicating that the interaction was of a pharmacodynamic type. In contrast M3G pretreatment increased the M6G induced locomotor activity. M3G pretreatment increased serum and brain M6G concentrations to an extent indicating that this interaction was mainly of a pharmacokinetic type. In conclusion our results disclose complicated interactions between morphine and its two metabolites with respect to induction of locomotor activity and possibly also with respect to mechanisms related to drug reward. PMID- 17343906 TI - Prazosin administered prior to inescapable stressor blocks subsequent exaggeration of acoustic startle response in rats. AB - Exposure to traumatic stress can result in a number of pathophysiological conditions, including post-traumatic stress disorder (PTSD). PTSD is characterized by a number of persistently heightened physiological and behavioral indicators, including increased sensory arousal and increased startle response. Similar effects can be seen in an animal model of PTSD in which stress results from restraint and inescapable tailshocks to rats. The present study used this animal model to investigate the effects of prazosin, an alpha(1) adrenoceptor antagonist, on stress-induced elevation of acoustic startle response (ASR). To investigate this, male Sprague-Dawley rats were injected with 0.5 mg/kg of prazosin 30 min before restraint and inescapable tail shock on three consecutive days. ASR testing was performed 1, 4, 7 and 10 days post-stress and compared to baseline and control values. Results show a significant reduction of ASR hyperarousal in the group treated with prazosin prior to stress compared to vehicle treated stressed animals and controls. Pre-stress treatment with lower levels of prazosin (0.25, 0.1 and 0.05 mg/kg) showed similar results. These findings further implicate an alpha(1) adrenoceptor role in the pathophysiological response to traumatic stress and suggest a potential preventative role for prazosin. PMID- 17343907 TI - A polymerase chain reaction for the detection of Brucella canis in semen of naturally infected dogs. AB - The objective was to evaluate a PCR assay for the detection of Brucella canis in canine semen, comparing its performance with that of bacterial isolation, serological tests and PCR assay of blood. Fifty-two male dogs were examined clinically to detect reproductive abnormalities and their serum was tested by the rapid slide agglutination test, with and without 2-mercaptoethanol (2ME-RSAT and RSAT, respectively). In addition, microbiological culture and PCR assays were performed on blood and semen samples. The findings of the semen PCR were compared (Kappa coefficient and McNemar test) to those of blood PCR, culture of blood and semen, RSAT, and 2ME-RSAT. Nucleic acid extracts from semen collected from dogs not infected with B. canis were spiked with decreasing amounts of B. canis RM6/66 DNA and the resulting samples subjected to PCR. In addition, semen samples of non infected dogs were spiked with decreasing amounts of B. canis CFU and the resulting suspensions were used for DNA extraction and amplification. Of the 52 dogs that were examined, the following tests were positive: RSAT, 16 (30.7%); 2ME RSAT, 5 (9.6%); blood culture, 14 (26.9%); semen culture, 11 (21.1%); blood PCR, 18 (34.6%); semen PCR, 18 (34.6%). The PCR assay detected as few as 3.8 fg of B. canis DNA experimentally diluted in 444.9 ng of canine DNA (extracted from semen samples of non-infected dogs). In addition, the PCR assay amplified B. canis genetic sequences from semen samples containing as little as 1.0 x 10(0) cfu/mL. We concluded that PCR assay of semen was a good candidate as a confirmatory test for the diagnosis of brucellosis in dogs; its diagnostic performance was similar to blood culture or blood PCR. Furthermore, the PCR assay of semen was more sensitive than the 2ME-RSAT or semen culture. Examination of semen by PCR should be included for diagnosis of brucellosis prior to natural mating or AI; in that regard, some dogs that were negative on serological and microbiological examinations as well as blood PCR were positive on PCR of semen. PMID- 17343908 TI - Interaction of an Fe derivative of TMAP (Fe(TMAP)OAc) with DNA in comparison with free-base TMAP. AB - We investigated the interaction of meso-tetrakis (N-para-methylanilium) porphyrin (TMAP) in its free base and Fe(II) form (Fe(TMAP)OAc) as a new derivative, with high molecular weight DNA at different ionic strengths, using various spectroscopic methods and microcalorimetry. The data obtained by spectrophotometery, circular dichroism (CD), fluorescence quenching and resonance light scattering (RLS) have demonstrated that TMAP association with DNA is via outside binding with self-stacking manner, which is accompanied with the "end-on" type complex formation in low ionic strength. However, in the case of Fe(TMAP)OAc, predominant mode of interaction is groove binding and after increasing in DNA concentration, unstable stacking-type aggregates are formed. In addition, isothermal titration calorimetric measurements have indicated the exothermic process of porphyrins binding to DNA, but the exothermisity in metal derivative of porphyrin is less than the free base. It confirmed the formation of a more organized aggregate of TMAP on DNA surface. Interactions of both porphyrins with DNA show high sensitivity to ionic strength. By addition of salt, the downfield CD signal of TMAP aggregates is shifted to a higher wavelength, which indicates some changes in the aggregates position. In the case of Fe(TMAP)OAc, addition of salt leads to changes in the mode of binding from groove binding to outside binding with self-stacking, which is accompanied with major changes in CD spectra, possibly indicating the formation of "face-on" type complex. PMID- 17343910 TI - On the use of fluorescent probes to distinguish Ca2+ from Zn2+ in models of excitotoxicity. PMID- 17343909 TI - BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential. AB - The specific role played by NCX1, NCX2, and NCX3, the three isoforms of the Na+/Ca2+ exchanger (NCX), has been explored during hypoxic conditions in BHK cells stably transfected with each of these isoforms. Six major findings emerged from the present study: (1) all the three isoforms were highly expressed on the plasma membranes of BHK cells; (2) under physiological conditions, the three NCX isoforms showed similar functional activity; (3) hypoxia plus reoxygenation induced a lower increase of [Ca2+]i in BHK-NCX3-transfected cells than in BHK NCX1- and BHK-NCX2-transfected cells; (4) NCX3-transfected cells were more resistant to chemical hypoxia plus reoxygenation than NCX1- and NCX2-transfected cells. Interestingly, such augmented resistance was eliminated by CBDMD (10 microM), an inhibitor of NCX and by the specific silencing of the NCX3 isoform; (5) chemical hypoxia plus reoxygenation produced a loss of mitochondrial membrane potential in NCX1- and NCX2-transfected cells, but not in NCX3-transfected cells; (6) the forward mode of operation in NCX3-transfected cells was not affected by ATP depletion, as it occurred in NCX1- and NCX2-transfected cells. Altogether, these results indicate that the brain specifically expressed NCX3 isoform more significantly contributes to the maintenance of [Ca2+]i homeostasis during experimental conditions mimicking ischemia, thereby preventing mitochondrial delta psi collapses and cell death. PMID- 17343911 TI - Voltage-dependent Ba2+ permeation through store-operated CRAC channels: implications for channel selectivity. AB - Store-operated Ca2+ entry through CRAC channels is a major route for Ca2+ influx in non-excitable cells. Studies on store-operated channel selectivity using fluorescent dyes have found that the channels are impermeable to Ba2+. Furthermore, in such studies, agonists have been reported to increase Ba2+ influx, leading to the conclusion that additional Ca2+ entry pathways (permeable to Ba2+) co-exist with the Ba2+-impermeable store-operated channels. However, patch clamp experiments demonstrate that CRAC channels are permeable to Ba2+. We have addressed this paradox using fluorescence measurements and whole cell patch clamp recordings of ICRAC. In store-depleted cells loaded with fura 2, Ba2+ application results in a slower and smaller rise in fluorescence than is the case with Ca2+. Ba2+, unlike Ca2+, depolarises the membrane potential by approximately 40 mV, due to rapid block of an inwardly rectifying K+ current. Although Ba2+ permeates CRAC channels at very negative potentials in patch clamp recordings, Ba2+ permeation is steeply voltage-dependent. This combination of Ba2+-dependent depolarisation and voltage-dependent Ba2+ permeation accounts for the apparent lack of Ba2+ permeation through store-operated channels seen in fluorescence experiments. Our findings identify major limitations with the use of Ba2+ as a surrogate for Ca2+ in probing Ca2+ entry pathways and raise the possibility that some of the previous reports proposing multiple Ca2+ entry pathways based on Ba2+ entry into fura 2-loaded cells could be explained by voltage-dependent Ba2+ permeation through CRAC channels. PMID- 17343912 TI - Iap2 is required for a sustained response in the Drosophila Imd pathway. AB - Fruit flies have effective immune response against Gram-negative bacteria. Upon infection, early JNK-signaling pathway mediated response is followed by the action of the Immune deficiency (Imd) signaling cascade, a Drosophila equivalent of mammalian TNF-receptor pathway, leading to the release of antimicrobial peptides. Recently, Tak1-binding protein 2 (Tab2) and Inhibitor of apoptosis 2 (Iap2) were identified as components of the Imd pathway. In this study, we carried out a genome-wide kinetic analysis of the role of Tab2 and Iap2 for immune response in Drosophila S2 cells using oligonucleotide microarrays. Tab2 RNAi abolished the induction of all immune response genes in S2 cells indicating its requirement for signaling both via the Imd and the JNK pathway. The role of Iap2 was more specific. Kinetic analysis indicated that Iap2 is required to sustain antimicrobial peptide gene expression in S2 cells. Furthermore, inactivation of Iap2 by RNAi resulted in impaired microbial resistance in Drosophila in vivo. PMID- 17343913 TI - Profile of acute immune response in Chinese amphioxus upon Staphylococcus aureus and Vibrio parahaemolyticus infection. AB - Amphioxus is traditionally considered as the living invertebrate most closely related to vertebrate. However, no systematic study was performed about how the amphioxus defends against the microbial invasion. Here we reported a profile of gene transcription after Staphylococcus aureus (S.c) and Vibrio parahaemolyticus (V.p) challenged by suppression subtractive hybridization (SSH). When compared with mammals, amphioxus has the same acute immune defense genes (lectins, metalloproteinase, lysozymes and antimicrobial peptide, etc.) as well as a similar pattern and level of temporal gene expression. In contrast, amphioxus was demonstrated to have some novel acute immune response genes in response to the microbial challenge, such as apextrin and dermatopontin, which have a 3500-fold and 900-fold induction after the V.p infection, respectively, suggesting new functions in early immune system for these two genes. Our results reported for the first time a profile of primitive immune system defense against infection in protochordate. PMID- 17343914 TI - Naturally occurring cobalamins have antimalarial activity. AB - The acquisition of resistance by malaria parasites towards existing antimalarials has necessitated the development of new chemotherapeutic agents. The effect of vitamin B(12) derivatives on the formation of beta-haematin (synthetic haemozoin) was determined under conditions similar to those in the parasitic food vacuole (using chloroquine, a known inhibitor of haemozoin formation for comparison). Adenosylcobalamin (Ado-cbl), methylcobalamin (CH(3)-cbl) and aquocobalamin (H(2)O cbl) were approximately forty times more effective inhibitors of beta-haematin formation than chloroquine, cyanocobalamin (CN-cbl) was slightly more inhibitory than chloroquine, while dicyanocobinamide had no effect. It is proposed that the cobalamins exert their inhibitory effect on beta-haematin formation by pi interactions of their corrin ring with the Fe(III)-protoporphyrin ring and by hydrogen-bonding using their 5,6-dimethylbenzimidazole/ribose/sugar side-chain. The antimalarial activity for the cobalamins (Ado-cbl>CH(3)-cbl>H(2)O-cbl>CN-cbl) was found to be less than that for chloroquine or quinine. Ado-cbl, CH(3)-cbl and CN-cbl do not accumulate in the parasite food vacuole by pH trapping, but H(2)O cbl does. Unlike humans, the malaria parasite has only one enzyme that uses cobalamin as a cofactor, namely methionine synthase, which is important for growth and metabolism. Thus cobalamins in very small amounts are necessary for Plasmodium falciparum growth but in larger amounts they display antimalarial properties. PMID- 17343915 TI - A large outbreak of tinea capitis in a primary school. PMID- 17343916 TI - Guiding empirical antibiotic therapy in orthopaedics: The microbiology of prosthetic joint infection managed by debridement, irrigation and prosthesis retention. AB - OBJECTIVES: This study describes the microbiological spectrum of prosthetic joint infection (PJI) managed by debridement, washout and retention and so guides the choice of empirical antibiotics within this patient group. METHODS: We performed a retrospective review of all patients admitted to our specialist tertiary unit for PJI who were managed with debridement and irrigation or arthroscopic washout of infected prosthetic joints between 1st January 1998 and 30th April 2003. Clinical and microbiological data sets were analysed using the Access database. RESULTS: One hundred and twelve patients met the criteria for inclusion. 69% received their surgical intervention in the first three months after implantation ('early') and 21% after 12 months. Overall the most frequently isolated organisms were coagulase negative staphylococci (47% patients) and methicillin-sensitive Staphylococcus aureus (MSSA, 44% patients). 8% grew methicillin-resistant Staphylococcus aureus (MRSA) and 7% grew anaerobes. Most Gram-negative isolates were resistant to cefuroxime; all were sensitive to meropenem. Eighty-six percent of polymicrobial cultures occurred in early infections when 47% of patients grew more than one organism. MSSA was the most frequently isolated organism at all time points. CONCLUSIONS: Most infections involved staphylococci. MRSA was infrequently isolated. Most polymicrobial infections occurred in early infection. A high rate of resistance to cephalosporins among Gram-negative organisms justifies the use of a broader agent such as a carbapenem in the early empirical antibiotic regime for PJI. PMID- 17343917 TI - Soluble triggering receptor expressed on myeloid cells-1 is not a sufficient biological marker for infection of the urinary tract. PMID- 17343918 TI - Cortical electrode localization from X-rays and simple mapping for electrocorticographic research: The "Location on Cortex" (LOC) package for MATLAB. AB - Medically refractory epilepsy accounts for more than 30% of the epilepsy population. Scalp EEG electrodes have limited ability to localize seizure onset from deep structures and implantation of subdural electrodes with long term monitoring provides additional information. Apart from clinical application, this patient population provides a unique opportunity for acquiring electrocorticography data in research paradigms. We present a method for rapid localization of electrodes using lateral and anterior-posterior X-rays. Skull landmarks and proportions are used for co-registration with the standardized Talairach coordinate system. This MATLAB-based "Location on Cortex" (LOC) package facilitates rapid visualization of clinical and experimental data in a user friendly manner. PMID- 17343919 TI - Antioxidant activity of N-acetylcysteine, flavonoids and alpha-tocopherol on endometrial cells in culture. AB - An appropriate local environment is necessary for successful implantation. Oxidative stress is implicated in the pathogenesis of several pathologies, and may contribute to early pregnancy failure. Antioxidant therapies have been studied in infertility. In this study, we have assessed the antioxidant activity of N-acetylcysteine (NAC), flavonoids (quercetin, catechin) and alpha-tocopherol in an oxidative model of endometrial cells (RL95). Endometrial cells were incubated at several hydrogen peroxide concentrations. Antioxidant effects of NAC (15 mM), quercetin (150 microM), catechin (150 microM) and alpha-tocopherol included in liposomes (1.6 microg) were assessed by measuring cell viability by the MTT assay. Alpha-tocopherol-liposomes taken up by endometrial cells were assessed by HPLC. All liposomes used were able to introduce alpha-tocopherol into cells. The antioxidant effect of NAC and quercetin improved the viability of oxidised cells, and this effect was observed when the oxidant and antioxidant were coincubated. No viability change occurred when the antioxidant was added before or after the oxidant. The antioxidant effect of NAC was better than that of quercetin. When catechin or alpha-tocopherol were used in the same conditions, no antioxidant effect was detected in cells in culture. These results demonstrate that NAC and quercetin are good H2O2 scavengers. PMID- 17343920 TI - Are self-reports valid for schizophrenia patients with poor insight? Relationship of unawareness of illness to psychological self-report instruments. AB - This investigation aimed to determine whether impaired insight influences the validity of self-report test scores in schizophrenia and schizoaffective disorder. 274 outpatients enrolled in work rehabilitation completed the Beck Depression Inventory (BDI), Eysenck Personality Questionnaire (EPQ), Bell Object Relations and Reality Testing Inventory (BORRTI), and NEO-Five Factor Inventory (NEO-FFI). Self-report scores were compared to clinician's ratings on comparable personality and symptom dimensions on the Positive and Negative Syndrome Scale (PANSS), the Work Behavior Inventory (WBI), and the Quality of Life Scale (QLS). The influence of insight was determined using the Scale for Unawareness of Mental Disorder (SUMD). In the first analysis, clinician SUMD ratings of patient insight were associated with self-report accuracy. In a second analysis, patients were categorized into good and poor insight groups based on SUMD ratings and compared on self-report and clinician report variables. Results suggest that poor insight patients accurately report less Neuroticism and Agreeableness, and more Psychoticism than good insight patients, but individuals with poor insight wish to present themselves as more extraverted than they actually are, and they are likely to be more certain of their perceptions than they should be. It appears that self-report measures may be valid for most personality and symptom domains. PMID- 17343921 TI - The impaired response of NK cells from HIV-infected progressor patients to A class CpG oligodeoxynucleotides is largely dependent of a decreased production of IL-12. AB - We have reported that NK cells from HIV-infected progressors showed a markedly lower IFN-gamma production in response to an A-class CpG oligodeoxynucleotide as compared to LTNP subjects and healthy HIV-negative individuals. This functional defect was not related to the number of circulating plasmacytoid dendritic cells, nor to the alpha-interferon secreted. In contrast, defective response correlated negatively with the frequency of myeloid dendritic cells. Furthermore, peripheral blood mononuclear cells from LTNPs as well as those from some healthy HIV negative donors secreted large amounts of IL-12 in unstimulated cultures and in response to the CpG-ODN whereas, HIV-progressor cells showed impaired responses and low level of spontaneous secretion. The addition of a monoclonal anti-IL-12 reduced the response to the CpG-ODN in a dose-dependent manner. These results suggest that the impaired response of NK cells to the CpG-ODN in HIV-progressors is largely dependent on a decreased production of IL-12. PMID- 17343922 TI - Intrathecal antibody production in an animal model of multiple sclerosis. AB - Although the central nervous system (CNS) is thought to be immunoprivileged, under special circumstances it can produce antibody. Antibody production within the CNS, called intrathecal antibody production (ITAbP), is a prominent feature of neurological infections and inflammatory diseases, and is thought to possibly contribute to disease in multiple sclerosis (MS), but it has not been extensively studied. We investigated ITAbP in a viral model of MS. ELISpot, real-time RT-PCR for IgG mRNA in CNS tissue, and CSF analysis were used to assess ITAbP in two types of SJL mice infected with one of two strains of Theiler's murine encephalomyelitis virus (TMEV). The amplitude of ITAbP increased during the first 4 months of infection. TMEV viral load remained high during the course of the infection, which likely was the main stimulus for ITAbP, since within samples of infected CNS tissues, levels of IgG gene expression were highly correlated with viral RNA levels, and a large percentage of intrathecally produced antibody was directed against TMEV. This study provides the first extensive analysis of ITAbP in TMEV infection, and demonstrates that, in this animal model of MS, antibody production within the CNS is likely driven by the presence of the causative pathogen. PMID- 17343923 TI - Time course of tissue remodelling and electrophysiology in the rat sciatic nerve after spiral cuff electrode implantation. AB - Implantation of nerve cuff electrodes induces inflammatory cell infiltration and loose connective tissue accumulation. Along with time, morphological changes evolve towards a thicker epi/perineurium as part of mechanisms that protect nerve functionality when a foreign body is wrapped around it. The rise in electrode impedance is linked to the nature of the epineurial tissue. Changes involve an increased expression of neuroprotective factors that is stronger in the endoneurium with axonal degeneration. Our data indicate that epineurial and endoneurial changes after electrode cuff implantation are part of axonal protection mechanisms. Their control is important to improve the yield of FES applications. PMID- 17343924 TI - Scarf pins sharp metallic tracheobronchial foreign bodies: presentation and management. AB - OBJECTIVES: Scarf pin inhalation is a cultural hazard in the Middle East young girls. So the aim of this work is to study the presentation of inhaled sharp airway foreign bodies (AFB) and its management. METHODS: Clinical and radiological presentation of inhaled sharp AFB was studied prospectively in 20 young females. All the sharp pins was extracted using rigid bronchoscopes with grasping forceps in 11 and magnetic extractor in 9. RESULTS: The most common presentation after inhalation was penetration syndrome (70%) (sudden onset of chocking and intractable cough). The distribution of AFBs was more significantly in the proximal 90% than the distal (p<0.05). It was significantly more in the left side (65%) than in the right side bronchial tree (5%) (p<0.05). The delay in diagnosis ranged from 6h to 1 week, with no complications on extraction. CONCLUSION: Scarf pins aspiration in females can be mainly presented with penetration syndrome. The site at presentation is mainly in left main bronchus. Early intervention, using rigid bronchoscopes with extraction using grasping forceps or magnetic extractor allowed easy and safe removal. Careful handling of these potentially sharp objects away from the mouth can prevent this critical problem. PMID- 17343925 TI - Influence of smoking on developing cochlea. Does smoking during pregnancy affect the amplitudes of transient evoked otoacoustic emissions in newborns? AB - OBJECTIVE: Maternal tobacco smoking has negative effects on fetal growth. The influence of smoking during pregnancy on the developing cochlea has not been estimated, although smoking has been positively associated with hearing loss in adults. The objective of this study was to determine the effects of maternal smoking on transient evoked otoacoustic emissions (TEOAEs) of healthy neonates. METHODS: This study was undertaken as part of neonatal screening for hearing impairment and involved both ears of 200 newborns. Newborns whose mothers reported smoking during pregnancy (n=200 ears) were compared to a control group of newborns (n=200 ears), whose mothers were non-smokers. Exposure to tobacco was characterized as low (<5 cigarettes per day, n=88 ears), moderate (5< or =cigarettes per day<10, n=76) or high (> or =10 cigarettes per day, n=36). RESULTS: In exposed neonates, TEOAEs mean response (across frequency) and mean amplitude at 4000Hz was significantly lower than in non-exposed neonates. Comparisons between exposed newborns' subgroups revealed no significant differences. However, by comparing each subgroup to control group, we found statistically significant decreases of TEOAEs amplitudes at 4000Hz for all three groups. Mean TEOAEs responses of highly exposed newborns were also significantly lower in comparison to our control group. CONCLUSION: In utero, exposure to tobacco smoking seems to have a small impact on outer hair cells. These effects seem to be equally true for all exposed newborns, regardless of the degree of exposure. Further studies are needed in order to establish a potential negative effect of maternal smoking on the neonate's hearing acuity. PMID- 17343926 TI - Cerclage sphincter pharyngoplasty: a new technique for velopharyngeal insufficiency. AB - OBJECTIVES: Several surgical techniques are available for the treatment of velopharyngeal insufficiency (VFI). Each method has its own complications and non dynamic roles. So the aim of this study was to present a novel physiological surgical technique designed by the author for reconstruction of the velopharyngeal sphincter in VFI. METHODS: This prospective study included six patients with VFI (two males and four females) with ages from 5 to 20 years (mean: 12.50 years). Speeches, nasopharyngeal and oral endoscopies for velopharyngeal valve closure were measured according to a 5-point scale where 0 was equivalent to normal and 4 meant a severe (constant) deviation. They were scheduled for cerclage sphincter pharyngoplasty after failure of appropriate speech therapy. Under general anaesthesia and the patient in semiflower's position; two level cerclages (1-0 polypropylene suture materials) were inserted behind the muscles of the velopharynx. The first at the level of junction of posterior and middle one-thirds of the soft palate passing through soft palate, left lateral pharyngeal wall, posterior pharyngeal wall, right lateral pharyngeal wall and the soft palate. The second was at 3mm in front of the latter. The surgical technique was described in details. RESULTS: Before surgery five patients (83.3%) had sever hypernasality (rating scale 3). After the cerclage operation and speech therapy four patients (66.6%) significantly improved to normal nasality (rating scale 0) and the remaining two patients improved to mild and moderate hypernasality (rating scale 1 and 2), respectively (p<0.05). By endoscopy the closing activity was (rating scale 3) in five patients (83.3%) and (rating scale 2) in one patient (18%). After the cerclage operation and speech therapy five patients (83.3%) changed significantly to complete closure (rating scale 0) and to (rating scale 1) in one patient (p<0.05). CONCLUSIONS: Cerclage sphincter pharyngoplasty is a new procedure designed by the author in VFI. It helps the velopharynx to function physiologically in three-dimensional patterns without dependency on the type of closure. Also it is an easy technique; without tissue flaps transfer, upper airway obstruction or hyponasality. PMID- 17343927 TI - Detection of enteroviruses by reverse-transcriptase polymerase chain reaction in cell culture negative stool specimens of patients with acute flaccid paralysis. AB - The aim of this study was the detection of a 114 base pairs amplicon in 5' non translated region of enterovirus genome in stool specimens of patients with acute flaccid paralysis (AFP) which were negative on cell culture. One hundred and twenty stool specimens were collected from AFP cases and tested with cell culture (RD, L20B and Hep2 cell lines). RT-PCR was carried out for the specimens with negative cell culture result. A 10% raise in enterovirus detection was observed with RT-PCR. This increased sensitivity can improve the detection of enterovirus serotypes which grow poorly in cell culture, and can thus alter significantly the medical care of patients with acute flaccid paralysis. PMID- 17343928 TI - Human monoclonal antibody against Hepatitis B virus surface antigen (HBsAg). AB - Hepatitis B virus (HBV) is one of the main pathogens responsible for hepatitis and hepatocellular carcinoma. Human plasma-derived Hepatitis B immune globulin (HBIG) is being used for prophylactic and liver transplantation currently. However, it may be necessary to replace a HBIG with a recombinant one because of limited availability of human plasma with high anti-HBsAg antibody titer and possible contamination of human pathogens. A Chinese hamster ovary (CHO) cell line, HB-C7A, was established which produces a fully human IgG1 that binds HBsAg. The HB-C7A exhibits approximately 2600 units/mg of antibody. The affinity (K(a)) of HB-C7A is 1.1 x 10(8) M(-1) by Biacore analysis and estimated 6.7-fold higher than that of Hepabig (a plasma-derived HBIG from Green Cross Corp., Yongin, Korea) by competition ELISA. The HB-C7A recognizes the conformational "a" determinant of HBsAg and binds HBV particle more efficiently than the Hepabig. The HB-C7A binds to HBV-infected human liver tissue but does not bind to normal human tissues. This HB-C7A has several advantages compared to plasma-derived Hepabig such as activity, safety and availability. PMID- 17343929 TI - Toxicity of single walled carbon nanotubes to rainbow trout, (Oncorhynchus mykiss): respiratory toxicity, organ pathologies, and other physiological effects. AB - Mammalian studies have raised concerns about the toxicity of carbon nanotubes (CNTs), but there is very limited data on ecotoxicity to aquatic life. We describe the first detailed report on the toxicity of single walled carbon nanotubes (SWCNT) to rainbow trout, using a body systems approach. Stock solutions of dispersed SWCNT were prepared using a combination of solvent (sodium dodecyl sulphate, SDS) and sonication. A semi-static test system was used to expose rainbow trout to either a freshwater control, solvent control, 0.1, 0.25 or 0.5 mgl(-1) SWCNT for up to 10 days. SWCNT exposure caused a dose-dependent rise in ventilation rate, gill pathologies (oedema, altered mucocytes, hyperplasia), and mucus secretion with SWCNT precipitation on the gill mucus. No major haematological or blood disturbances were observed in terms of red and white blood cell counts, haematocrits, whole blood haemoglobin, and plasma Na(+) or K(+). Tissue metal levels (Na(+), K(+), Ca(2+), Cu, Zn and Co) were generally unaffected. However some dose-dependent changes in brain and gill Zn or Cu were observed (but not tissue Ca(2+)), that were also partly attributed to the solvent. SWCNT exposure caused statistically significant increases in Na(+)K(+) ATPase activity in the gills and intestine, but not in the brain. Thiobarbituric acid reactive substances (TBARS) showed dose-dependent and statistically significant decreases especially in the gill, brain and liver during SWCNT exposure compared to controls. SWCNT exposure caused statistically significant increases in the total glutathione levels in the gills (28%) and livers (18%), compared to the solvent control. Total glutathione in the brain and intestine remained stable in all treatments. Pathologies in the brain included possible aneurisms or swellings on the ventral surface of the cerebellum. Liver cells exposed to SWCNT showed condensed nuclear bodies (apoptotic bodies) and cells in abnormal nuclear division. Overt fatty change or wide spread lipidosis was absent in the liver. Fish ingested water containing SWCNT during exposure (presumably stress-induced drinking) which resulted in precipitated SWCNT in the gut lumen and intestinal pathology. Aggressive behaviour and fin nipping caused some mortalities at the end of the experiment, which may be associated with the gill irritation and brain injury, although the solvent may also partly contributed to aggression. Overall we conclude that SWCNTs are a respiratory toxicant in trout, the fish are able to manage oxidative stress and osmoregulatory disturbances, but other cellular pathologies raise concerns about cell cycle defects, neurotoxicity, and as yet unidentified blood borne factors that possibly mediate systemic pathologies. PMID- 17343930 TI - Structural studies on Plasmodium vivax merozoite surface protein-1. AB - Plasmodium vivax infection is the second most common cause of malaria throughout the world. Like other Plasmodium species, P. vivax has a large protein complex, MSP-1, located on the merozoite surface. The C-terminal MSP-1 sub-unit, MSP 1(42), is cleaved during red blood cell invasion, causing the majority of the complex to be shed and leaving only a small 15kDa sub-unit, MSP-1(19), on the merozite surface. MSP-1(19) is considered a strong vaccine candidate. We have determined the solution structure of MSP-1(19) from P. vivax using nuclear magnetic resonance (NMR) and show that, like in other Plasmodium species, it consists of two EGF-like domains that are oriented head-to-tail. The protein has a flat, disk-like shape with a highly charged surface. When MSP-1(19) is part of the larger MSP-1(42) precursor it exists as an independent domain with no stable contacts to the rest of the sub-unit. Gel filtration and analytical ultracentrifugation experiments indicate that P. vivax MSP-1(42) exists as a dimer in solution. MSP-1(19) itself is a monomer, however, 35 amino-acids immediately upstream of its N-terminus are sufficient to cause dimerization. Our data suggest that if MSP-1(42) exists as a dimer in vivo, secondary processing would cause the dissociation of two tightly linked MSP-1(19) proteins on the merozoite surface just prior to invasion. PMID- 17343931 TI - Cognitive function and its effects on the quality of life status in the patients with chronic obstructive pulmonary disease (COPD). AB - The objective of the present study was to determine the relationships between the cognitive function and quality of life in the patients with chronic obstructive pulmonary disease (COPD). Thirty-two patients with stable COPD (mean age 66.7+/ 2.5 years) and 26 healthy community residents (mean age 65.7+/-7.3 years) were included in the present study. Cognitive status was measured using a modified mini mental state examination (MMSE) and quality of life status using the health survey questionnaire short form-36 (SF-36). The patients with COPD were mildly hypoxemic and their lung function was significantly poorer than in the healthy group (p=0.001). The quality of life scores were lower in the patients with COPD than in the healthy subjects (p=0.01). Impaired cognitive function in the patients with COPD and healthy subjects was not found (the mean MMSE scores 24.8+/-2.0 versus 25.4+/-3.2 for COPD and healthy groups, respectively, p=0.49). No correlation was found between the SF-36 and MMSE and spirometric values in either of groups (p>0.05). In conclusion, the cognitive function of COPD patients with mild hypoxemia may not be impaired in spite of their poor quality of life status. PMID- 17343932 TI - Tako-Tsubo cardiomyopathy: NT-proBNP as a reliable parameter of a favourable prognosis? PMID- 17343933 TI - Association between decreased intra-thoracic impedance and ventricular tachyarrhythmias. PMID- 17343934 TI - Effects of irbesartan and perindopril on forearm reactive hyperemia and inflammatory process, in normotensive patients with coronary artery disease. PMID- 17343935 TI - Angioplasty for the late stent thrombosis, the new technical challenge: a single centre experience. AB - Late Angiographic Stent Thrombosis (LAST) following drug-eluting stent is quite a well recognised entity today with most reported cases having occurred following antiplatelet therapy withdrawal late after stent implantation. Angioplasty of these late thrombotic stent occlusions poses a new technical challenge quite different from usual native vessel thrombotic occlusions, an issue that has not been addressed at length primarily due to the limited numbers and stray nature of the reports. We herein report our experience with percutaneous intervention in five such cases of late stent thrombosis >2 years following drug-eluting stent implantation from a single centre. PMID- 17343936 TI - Soil microbial community analysis using two-dimensional polyacrylamide gel electrophoresis of the bacterial ribosomal internal transcribed spacer regions. AB - Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of digested genomic DNA has been previously used in comparative genomics studies of closely related bacteria species. However, a two-dimensional gel electrophoresis approach for examining microbial community structures in environmental samples has not yet been developed. We determined that it is theoretically possible to separate internal transcribed spacer regions (ITS) of bacterial communities into hundreds of operational taxonomic units (OTUs) using 2D-PAGE. Application of 2D-PAGE for separating Bacterial ITS sequences that have been PCR-amplified from replicate soil samples taken from along a Zn gradient resulted in reproducible gels containing hundreds of spots. Clear differences in spot patterns were observed between soil samples that differed in both sampling location and Zn content. The number of OTUs detected using 2D-PAGE of ITS regions was much greater than that observed using Automated Ribosomal Internal Transcribed Spacer Analysis (ARISA), Terminal Restriction Fragment Length Polymorphism (T-RFLP), or Denaturing Gradient Gel Electrophoresis (DGGE). Principal Component Analysis (PCA) of community spot patterns resulted in similar groupings of samples as those obtained using other molecular methods, however, excised spots were found to contain a far lower diversity of different sequences than excised ITS bands of the same length, as determined by RFLP analysis of excision clone libraries and subsequent sequencing of DNA eluted from excised spots. This increase in resolution makes 2D-PAGE of Bacteria ITS fragments from complex microbial communities a viable method for detecting differences between highly similar communities, as well as in streamlining follow-on sequencing efforts by reducing the level of homoplasy (co-migration of heterogeneous sequences) often seen in band-based community fingerprinting methods. PMID- 17343937 TI - Prostate brachytherapy in Europe: growth, practice and guidelines. PMID- 17343938 TI - Results of a prospective randomised trial comparing conventional radiotherapy to split course bifractionated radiation therapy in patients with nasopharyngeal carcinoma. AB - BACKGROUND AND PURPOSE: Nasopharyngeal carcinoma (NPC) is generally responsive to radiation therapy. However therapeutic results after conventional radiotherapy remain relatively poor especially for patients with locoregional advanced NPC. The aim of this study was to evaluate the impact of a split course bifractionated radiotherapy regimen in a phase III randomised trial. PATIENTS AND METHODS: From January 1997 to September 2003, 154 patients with M0 histologically proven NPC were treated in our institution. They were staged according to the American Joint Committee on Cancer - International Union Against Cancer (AJCC-UICC) 1986 TNM classification. Patients with locally advanced nodal disease (N2-N3) received induction chemotherapy. All patients were randomised to receive either conventional radiotherapy at 2 Gy/fraction/day, 5 days/week to 70 Gy/7 weeks or split course bifractionated radiotherapy at 1.6 Gy/fraction, twice daily, 5 days/week to 70.4 Gy/6 weeks. Response and toxicity were evaluated according to the WHO and RTOG criteria. RESULTS: Patients were well balanced between the two arms. The complete remission rate was 91% in conventional radiotherapy arm and 93% in bifractionated radiotherapy arm (p=0.3). There was more grade II-III skin fibrosis in experimental arm with a 5 year actuarial probability of 66% vs 52% (p=0.04). Locoregional and distant relapses occurred in 34% of cases in conventional arm and 38% in experimental arm (p=0.28). With a median follow-up of 56 months, the 5 year overall survival and the disease free survival rates were, respectively (71% and 61%), in conventional arm and (62% and 60%) in bifractionated arm, the difference being statistically non significant. COMMENTS: The present trial comparing conventional radiotherapy to a split course bifractionated radiation therapy failed to demonstrate significant improvement in locoregional control and survival in experimental arm which was associated with more grade II-III skin fibrosis. PMID- 17343939 TI - Contraindications to cisplatin based chemoradiotherapy in the treatment of cervical cancer in Sub-Saharan Africa. AB - BACKGROUND AND PURPOSE: We conducted a prospective study to assess the eligibility of patients presenting with cervical cancer in the developing world for chemoradiotherapy. MATERIAL AND METHODS: Patients with biopsy proven cervical cancer were eligible. Workup included history, examination, pre-treatment Karnofsky performance score, evaluation under anaesthesia to establish FIGO stage, complete blood count, renal and liver functions tests, HIV test and ultrasound of the abdomen and pelvis. EXCLUSION CRITERIA: stage IA, stage IV, HIV status positive, Karnofsky performance score <60, age >70 years, hydronephrosis, haemoglobin <8 g/dL, white cell count <2,000/microL, platelets <100,000/microL, creatinine >97 micromol/L. RESULTS: 314 patients were included. After workup, 47 patients (15.1%) were eligible for combined modality treatment and 190 (60.5%) were not eligible. Eligibility could not be established in 77 cases (24.4%). 37 (11.6%) of the group were HIV positive, HIV status was not established in 38.4% of cases. The most frequently encountered exclusion criteria were hydronephrosis and anaemia. Application of a haemoglobin cut off point of 8 g/dL for cisplatin based chemotherapy resulted in the exclusion of 55 (17.4%) patients. A limit of 10 g/dL excluded an additional 11 patients. Hydronephrosis was diagnosed on ultrasound in 99 (31.4%) patients. 56% had unilateral hydronephrosis, 44% had bilateral hydronephrosis. CONCLUSIONS: A small proportion of our patients with cervical cancer would benefit from chemoradiotherapy with concomitant cisplatin, illustrating the difficulties of applying "standard" treatment to the developing world. The introduction of national screening programmes and the provision of accessible radiotherapy facilities should be the major priorities in the developing world setting. PMID- 17343940 TI - Retrospective attenuation correction of PET data for radiotherapy planning using a free breathing CT. AB - PURPOSE: To evaluate the image quality of retrospectively attenuation corrected Positron Emission Tomography (PET) scans used for gross tumor volume (GTV) delineation in lung cancer patients. MATERIALS AND METHODS: Data of 13 lymph node positive lung cancer patients were acquired on separate CT and PET scanners under free breathing conditions (for radiotherapy planning). First we determined a protocol for CT/PET registration. Second, we compared the image quality of attenuation-corrected PET images using positron transmission images and CT images, in terms of signal-to-noise ratio (SNR) and lesion-to-background ratio (contrast). RESULTS: The largest differences between manual and automatic CT/PET registration were found in the anterior-posterior direction with a mean of 1.8 mm (SD 1.0 mm). Differences in rotations were always smaller than 1.0 degrees . The attenuation-corrected images using CT showed a larger SNR (mean 30%, SD 17%) and larger contrast (mean 14.0%, SD 8.5%) compared to attenuation-corrected images using positron transmission. For lymph nodes, the mean contrast was 16% (SD 6.4%) larger. CONCLUSIONS: This study demonstrated that attenuation correction based on CT provides a better image quality for GTV delineation than when using positron transmission for attenuation correction. Retrospective attenuation correction of PET scans based on registered CT is a good alternative for a dedicated PET/CT scanner if a free-breathing CT is available, e.g., for radiotherapy planning, and allows the use of CT with diagnostic quality for attenuation correction. PMID- 17343941 TI - Vertical asymmetries in pre-attentive detection of changes in motion direction. AB - Stimulus localization affects visual motion processing. Vertical asymmetries favouring lower visual field have been reported in event-related potentials (ERPs) and behavioural studies under different attention conditions. However, there are no studies examining such asymmetries to non-attended motion changes. The present study investigated whether the asymmetry in processing information from the upper and lower visual fields also affects the automatic detection of motion-direction changes as indexed by visual Mismatch Negativity (vMMN). We recorded vMMN to changes in sinusoidal gratings differing in motion direction presented in the periphery of visual field in three different locations: upper and lower (ULVF), upper (UVF) and lower (LVF) along the vertical meridian. The N2 component elicited to peripheral motion presented lower amplitudes when the UVF was stimulated. The vMMN elicited to infrequent motion-direction changes was present in all stimulation conditions. However, it was reduced to UVF stimulation. These results suggest that the visual system automatically detects motion-direction changes presented at both upper-lower visual fields; however they also indicate that the process is favoured when stimuli are presented in the LVF alone. PMID- 17343942 TI - The temporal representation of in-phase and anti-phase movements. AB - We have proposed that the stability of bimanual coordination is influenced by the complexity of the representation of the task goals. Here, we present two experiments to explore this hypothesis. First, we examined whether a temporal event structure is present in continuous movements by having participants vocalize while producing bimanual circling movements. Participants tended to vocalize once per movement cycle when moving in-phase. In contrast, vocalizations were not synchronized with anti-phase movements. While the in-phase result is unexpected, the latter would suggest anti-phase continuous movements lack an event structure. Second, we examined the event structure of movements marked by salient turn-around points. Participants made bimanual wrist flexion movements and were instructed to move 'in synchrony' with a metronome, without specifying how they should couple the movements to the metronome. During in-phase movements, participants synchronized one hand cycle with every metronome beat; during anti phase movements, participants synchronized flexion of one hand with one metronome beat and extension of the other hand with the next beat. The results are consistent with the hypothesis that the instability of anti-phase movements is related to their more complex (or absent) event representation relative to that associated with in-phase movements. PMID- 17343943 TI - Trunk and center of mass movements during gait in children with juvenile idiopathic arthritis. AB - Motion of the body center of mass (CoM) can often indicate the overall effect of the strategy of forward progression used. In the present study, focus is placed on trunk movements in the sagittal, coronal, and transverse/rotation plane, as well as placement of the CoM, during gait in children with juvenile idiopathic arthritis (JIA). Seventeen children with JIA, all with polyarticular lower extremity involvement were examined before and approximately two weeks after treatment with intra-articular cortico-steroid injections. Movement was recorded with a 6-camera 3D motion analysis system in both the children with JIA and in 21 healthy controls. Trunk and center of mass movements were compared between JIA and controls, and effects of intra-articular cortico-steroid treatment were evaluated. Children with JIA were more posteriorly tilted in the trunk, contrary to the common clinical impression, and had their CoM placed more posterior and off-centred, which may have been a result of pain. With such knowledge, it might be possible to better understand the effects of their pain and involvement, and ultimately to plan a treatment strategy for improving their gait patterns. PMID- 17343944 TI - Non-declarative sequence learning does not show savings in relearning. AB - Researchers have utilized the savings in relearning paradigm in a variety of settings since Ebbinghaus developed the tool over a century ago. In spite of its widespread use, we do not yet understand what type(s) of memory are measurable by savings. Specifically, can savings measure both declarative and non-declarative memories? The lack of conscious recollection of the encoded material in some studies indicates that non-declarative memories may show savings effects, but as all studies to date have used declarative tasks, we cannot be certain. Here, we administer a non-declarative task and then measure savings in relearning the material declaratively. Our results show that while material outside of awareness may show savings effects, non-declarative sequence memory does not. These data highlight the important distinction between memory without awareness and non declarative memory. PMID- 17343945 TI - Sensitivity of muscle force estimates to variations in muscle-tendon properties. AB - The aim of this study was to determine the sensitivity of muscle force estimates to changes in some of the parameters which are commonly used to describe models of muscle-tendon actuation. The sensitivity analysis was performed on three parameters: optimal muscle-fiber length, muscle physiological cross-sectional area (PCSA), and tendon rest length. The muscles selected for the analysis were posterior gluteus medius/minimus, vasti, soleus, and sartorius. Each parameter was perturbed from its nominal value, and an optimization problem was solved to determine the relative influence of each parameter on the calculated values of muscle force. Muscle forces were calculated for a simulated cycle of normal walking. Parameter sensitivity was quantified using two new metrics: an integrated sensitivity ratio, which quantified the effect of changing a single parameter for any muscle on the time history of force developed by that muscle; and a summed cross-sensitivity ratio, which quantified the effect of changing one parameter for any muscle on the time histories of forces developed by all of the other muscles. The results showed that muscle force estimates for walking are most sensitive to changes in tendon rest length and least sensitive to changes in muscle PCSA. For soleus, for example, the integrated sensitivity ratios for tendon rest length were an order of magnitude greater than those for muscle-fiber length and PCSA. For vasti, the integrated sensitivity ratios for tendon rest length were twice as large as those for muscle-fiber length and nearly an order of magnitude greater than those for PCSA. Overall, changes in the tendon rest lengths of vasti and soleus and changes in the fiber length of vasti were most critical to model estimates of muscle force. Our results emphasize the importance of obtaining accurate estimates of tendon rest length and muscle-fiber length, particularly for those actuators that function as prime movers during locomotion (gluteus maximus, gluteus medius/minimus, vasti, soleus, and gastrocnemius). PMID- 17343946 TI - Re-examining structural constraints on the initiation of bimanual movements: the role of starting locations, movement amplitudes, and target locations. AB - Structural constraints affect the coordination of bimanual movements in ways that have been taken to suggest that the specification of different movement amplitudes is subject to strong intermanual interference effects. Most experiments taken to support this notion, however, confounded variations of movement amplitudes with symmetry in starting locations and variations in target location. The present experiment was designed to further investigate the relative influence of the parameters starting location, movement amplitude, and target location on bimanual movement coordination. Participants performed simultaneous reaching movements with the left and right hand from same and different starting locations to same and different target locations. On each trial, two movements could match on none, one, or all of the parameters. We assessed the influence of each parameter by comparing conditions in which only a single parameter matched between the two hands with conditions in which all parameters differed. The reaction-time data revealed some challenging results for previous studies: (1) same starting locations significantly delayed movement initiation; (2) specifying movement amplitudes had virtually no effect on movement initiation, whereas (3) selecting same target locations significantly benefited the bimanual responses. These findings cannot be taken to support the notion that amplitude specification affects the initiation of bimanual movements. Rather, they support the notion that the initial starting locations of the two hands and the selection of target locations decide about the ease with which we perform bimanual reaching movements. PMID- 17343947 TI - Human lumbar cord circuitries can be activated by extrinsic tonic input to generate locomotor-like activity. AB - We have demonstrated that non-patterned electrical stimulation of the lumbar cord can induce stepping-like activity in the lower limbs of complete spinal cord injured individuals. This result suggested the existence of a human lumbar locomotor pattern generator, which can convert a tonic input to a rhythmic motor output. We have studied the human lumbar cord in isolation from supraspinal input but under extrinsic tonic input delivered by spinal cord stimulation. Large diameter afferents within the posterior roots are directly depolarized by the electrical stimulation. These afferents project to motoneurons as well as to lumbar interneurons involved in the motor control of lower limbs. Stimulation at 25-50 Hz can elicit rhythmic alternating flexion/extension movements of the lower limbs in supine individuals. Reducing the tonic input frequency to 5-15 Hz initiates lower limb extension. Epidural stimulation applied during manually assisted treadmill stepping in complete spinal cord injured persons immediately increases the central state of excitability of lumbar cord networks and enhances stepping-like functional motor outputs. Sustained, non-patterned tonic input via the posterior roots can activate human lumbar cord networks. Pattern generating configurations of these multifunctional circuitries can be set-up depending on the stimulation parameters and particularly on the input frequency. PMID- 17343948 TI - Preface to the EWOMS special issue of Human Movement Science. PMID- 17343949 TI - Motor imagery: the relation between age and imagery capacity. AB - The imagination of motor actions forms not only a theoretical challenge for cognitive neuroscience but may also be seen as a novel therapeutic tool in neurological rehabilitation, in that it can be used for relearning motor control after damage to the motor system. However, since the majority of rehabilitation patients consist of older individuals it is relevant to know whether the capacity of mental imaging is compromised by age. Scores on the vividness of movement imagery questionnaire were obtained for 333 participants, divided in three age groups. Results showed that elderly participants were slightly worse in motor imagery capacity than younger participants, particularly in relation to motor imagery from an internal (first person) perspective. Furthermore, a possible relation between the level of physical activities and motor imagery capacity is discussed. PMID- 17343950 TI - An improved method to determine neuromuscular properties using force laws - From single muscle to applications in human movements. AB - We evaluate an improved method for individually determining neuromuscular properties in vivo. The method is based on Hill's equation used as a force law combined with Newton's equation of motion. To ensure the range of validity of Hill's equation, we first perform detailed investigations on in vitro single muscles. The force-velocity relation determined with the model coincides well with results obtained by standard methods (r=.99) above 20% of the isometric force. In addition, the model-predicted force curves during work loop contractions very well agree with measurements (mean difference: 2-3%). Subsequently, we deduce theoretically under which conditions it is possible to combine several muscles of the human body to model muscles. This leads to a model equation for human leg extension movements containing parameters for the muscle properties and for the activation. To numerically determine these invariant neuromuscular properties we devise an experimental method based on concentric and isometric leg extensions. With this method we determine individual muscle parameters from experiments such that the simulated curves agree well with experiments (r=.99). A reliability test with 12 participants revealed correlations r=.72-.91 for the neuromuscular parameters (p<.01). Predictions of similar movements under different conditions show mean errors of about 5%. In addition, we present applications in sports practise and theory. PMID- 17343951 TI - REMOVED: SARS Epidemiology From descriptive to mechanistic analyses. AB - This article has been removed, consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause. PMID- 17343952 TI - [Patient re-education before hip or knee arthroplasty]. PMID- 17343953 TI - Could preoperative rehabilitation modify postoperative outcomes after total hip and knee arthroplasty? Elaboration of French clinical practice guidelines. AB - OBJECTIVE: To develop clinical practice guidelines concerning preoperative rehabilitation for hip and knee total arthroplasty. METHOD: We used the SOFMER (French Physical Medicine and Rehabilitation Society) methodology, combining systematic literature review, collection of everyday clinical practice, and external review by a multidisciplinary expert panel, to develop the guidelines. Main outcomes considered in the recommendations were impairment, disability, medico-economic implications and postoperative complications. RESULTS: A preoperative rehabilitation program, comprising at least physical therapy and education, is recommended before total hip and knee arthroplasty. Occupational therapy could be combined with patient home visits. Isolated physical therapy before total knee arthroplasty (TKA) is not recommended. Multidisciplinary rehabilitation comprising at least occupational therapy and education is desirable for the most fragile patients because of major disability, co-morbidity or social problems. Complementary studies are required to confirm the impact of pre-operative rehabilitation before total hip and knee arthroplasty, to define components of rehabilitation and the patients most likely to benefit. CONCLUSION: Rehabilitation before total hip and knee arthroplasty contributes to reduced hospital length of and modifying discharge conditions. This rehabilitation necessitates the collaboration of qualified health care professionals in the educational topic and return-home preparation. Preoperative patient assessment is important. PMID- 17343954 TI - The burden of diabetes and its complications: trends and implications for intervention. AB - Much of the burden of diabetes is due to the development of vascular complications, including cardiovascular diseases, retinopathy and nephropathy. Improvements in patient management to promote tight control of glycaemia have helped to reduce the prevalence of microvascular complications, but cardiovascular diseases continue to be the leading cause of death in patients with type 2 diabetes. Globally, the number of people with diabetes is predicted to almost double over the next 30 years, with much of this increase occurring in developing countries. The growing prevalence of obesity is the major factor driving the increasing prevalence of type 2 diabetes, and the increase in obesity in adolescents is of particular concern. Consequently, the overall number of people with the vascular complications of diabetes is also predicted to increase. Prevention of diabetes is the best strategy for reducing the risk of complications, and screening of high-risk individuals is already being promoted in some countries. Lifestyle changes, focusing on diet, exercise and weight loss are effective in preventing diabetes in such people. However, more information is required about the long-term sustainability of these changes, and programmes also need to be adapted to meet the needs of developing countries. PMID- 17343955 TI - Dissecting the functional domain requirements of cortactin in invadopodia formation. AB - Cells degrade extracellular matrix (ECM) barriers at focal locations by the formation of membrane protrusions called invadopodia. Polymerization of the actin cytoskeleton is critical to the extension of these processes into the ECM. We used a short interference RNA/rescue strategy to investigate the role of cortactin in the formation of Src-induced invadopodia in 3T3 fibroblasts, and subsequent degradation of the ECM. Cortactin-depleted cells did not form invadopodia or degrade the ECM. Functional invadopodia were restored in cortactin depleted cells by expression of full-length cortactin, and fragments that contained the intact actin-binding repeats. Mutation of the three Src-targeted Tyr sites to Phe caused a loss in its rescuing ability, while mutation of the Erk phosphorylation sites had little effect on invadopodia formation. Interestingly, knock-down of cortactin did not affect the formation of lamellipodia and only slightly attenuated random cell motility. Our data shows that formation of functional invadopodia requires interaction between cortactin and filamentous actin, while interaction with SH3- and NTA-binding partners plays a less significant role. Furthermore, phosphorylation of cortactin by Src, but not by Erk, is essential for functional invadopodia formation. These results also suggest that cortactin plays a different role in invadopodia-dependent ECM degradation and lamellipodia formation in cell movement. PMID- 17343956 TI - Hedonic responses as predictors of food choice: flexibility and self-prediction. AB - The association between liking and choices of six cheeses was examined. Particular attention was in hedonic flexibility, i.e. the range of liking ratings, within an individual, leading to a choice. Second, the ability of respondents to predict their future liking and choices was studied. Respondents (62 females, 20-64 years) initially tasted and rated the cheeses blind and then chose three cheeses, 150 g piece of each, for home-use during the following week. They also predicted how their ratings of liking and choices would be next time, after a week. They returned to the laboratory to repeat the tasks twice, with one week intervals, thus a total of nine choices were made. Expectedly, the association between initial liking and frequencies of choice was strong (aggregate level correlation 0.70). Self-prediction of liking was less successful initially (r=0.56) than in the second session (r=0.68). In the first session, three choices were made within 1.3 points (mean) at the upper end of a 7-point scale, while nine choices were made within 2.7 points of initial ratings. Thus, the choices extended towards the initially less-liked cheeses in the second and third session. Although poor at precise prediction of their choices, the respondents fairly accurately knew which cheeses they would not choose. Hence, an important strategy in food choice may be to screen out unacceptable options and then alternate among the acceptable ones. PMID- 17343957 TI - In vivo insulin-mimetic activity of [N,N'-1,3-propyl bis(salicyladimine)]oxovanadium(IV). AB - [N,N'-1,3-Propyl-bis(salicyladimine)]oxovanadium(IV) - an oxovanadium complex has been tested for bioactivity as an insulin-enhancing agent. Its structure reveals that the vanadium(IV) ion is hexacoordinated and situated in a distorted octahedral environment. The complex was administered intragastrically to both normal and streptozotocin (STZ)-diabetic rats for two weeks. The results showed that the complex, at a dose of 10.0 and 20.0mgV.kg(-1), could lower the blood glucose level in STZ-diabetic rats and improve the response to an oral glucose challenge. This complex did not alter these parameters in normal rats. It was suggested that the complex exerted an antidiabetic effect in STZ-diabetic rats. PMID- 17343958 TI - Rationalization of physicochemical characters of oxazolyl thiosemicarbazone analogs towards multi-drug resistant tuberculosis: a QSAR approach. AB - The emergence of multi-drug resistant (MDR) strains of Mycobacterium tuberculosis and the continuing pandemic of tuberculosis emphasizes the urgent need for the development of new and potent anti-tubercular agents. In an effort to develop new and more effective agents to treat tuberculosis emphasis was focused on quantification of structure-activity relationship of oxazolyl thiosemicarbazone derivatives. The de novo analysis gave insight to some important structural features i.e. nitro group on phenyl ring at R(1) position is optimal for the activity and might be responsible for electronic interaction, while phenyl ring at R position interact with the hydrophobic pocket more effectively as compared to unsubstituted or methyl substituted analogs. Hansch approach offered the understanding and parameterization of interactions of the inhibitor with receptor. Similarly QSAR analysis gave some important physicochemical properties, i.e. empirical aromatic index (ARR) and 3D-MoRSE code value of scattering angle at 8A(-1). These two physicochemical properties shall be helpful in the development of more potent analogs. PMID- 17343959 TI - [Sequelae and quality of life in young adult survivors of childhood cancer]. AB - PURPOSE: The long-term survival rate of childhood cancer is around 70%, but cancer- and treatment-related sequelae and the risk of a second malignancy may impair the survivors' quality of life. METHODS: Fifty-four patients older than 18 years, treated for a cancer between 1988 and 1996, and considered as cured for at least 5 years, were asked to participate. Data on cancer, treatment and sequelae were extracted from the Rhone-Alpes childhood cancer registry and from the medical charts. Health-related quality of life was assessed with the SF-36 scale. Lifestyle, educational level, present occupation, subjective health, and worries were assessed with a detailed questionnaire. RESULTS: Forty-three young adult patients participated (16 female, 27 male, mean age 23 [range: 18-32]). Primary cancers were leukaemias (35%), lymphomas (19%), solid tumors (34%) and central nervous system tumors (12%). Nine percent of the subjects had received cranio spinal radiotherapy, and 14% a total body irradiation followed by bone marrow transplantation. Two patients (5%) had developed a second malignancy, 30% have an endocrine insufficiency, 14% have neurological or psychological impairment, and 21% have orthopaedic sequelae. Health-related quality of life of the population as a whole, as assessed by SF-36, is close to normative data published for healthy population of that age. Female gender, certain types of cancer (neuroblastoma, bone tumors and carcinomas), and the presence of endocrine sequelae are predictors of a worse quality of life. Only 3 patients (7%) declared having had to shorten their education because of their cancer; 63% are currently employed, 25% are students or apprentices. Worries about fertility are often mentioned; half of the subjects declare having received no formal instruction about their medical follow-up in adult age. CONCLUSION: Although the quality of life of young adult survivors of childhood cancer as a whole does not seem very much altered, many of these survivors experience adverse sequelae warranting medical and psychological attention. Some of their preoccupations, such as worries about reproductive capacity and inheritability of their cancer, are often ignored. PMID- 17343960 TI - Enhancement of intranasal vaccination with recombinant chain A ricin vaccine (rRV) in mice by the mucosal adjuvants LTK63 and LTR72. AB - Intranasal (i.n.) vaccination of mice with three doses of 40 microg of rRV stimulated low anti-ricin ELISA and neutralizing antibody responses, which were only marginally protective against aerosol-delivered 5-10 LD(50) of ricin toxin. To enhance the protection, and to reduce the lung injury of vaccinated mice that survived ricin toxin challenge, the mucosal adjuvant LTK63 or LTR72, two mutants of Escherichia coli LT enterotoxin adjuvant was administered with rRV. The safety of intranasally administered LTR63 was assessed as well. With 4, 2, or l microg of LTR63, the anti-ricin ELISA serum immunoglobulin geometric mean titer (GMT) increased up to 147-, 356-, 493-, and 17-fold for IgG, IgG1, IgG2a, and IgA, respectively. The comparable increases for GMTs of IgG and IgG1 in the presence LTR72 were up to 147-, and 617-fold, respectively. All three dose levels of LTK63 enhanced the ELISA GMTs in the lung lavage up to 192-, 22-, 4-, and 5-fold for IgG, IgG1, IgG2a, and IgA, respectively. Compared to GMT of rRV alone, the serum neutralizing antibody GMTs for the three dose levels were enhanced up to 11-fold with LTK63. LTK63 augmented the ricin-related lymphoproliferative response of the cultured spleen lymphocytes and of the isolated CD4+ T lymphocytes. In the cultured lymphocytes, LTK63 stimulated predominantly TH1 cytokines. While only 10% of the mice that were vaccinated with rRV survived lethal challenge, in the presence of LTK63 or LTR72, the respective survival rates were augmented to 100%. Compared to the surviving mice vaccinated with rRV alone, the vaccine with LTK63 or LTR72 did not attenuate the extent of the ricin-related lung injury at a single or two time-points, respectively. Safety of LTK63 administration was indicated by the absence of histopathological changes in every organ, including the lungs and in the central nervous systems (CNS) of the mice during the entire 92 days of the study. In the nasal passages of the mice that received LTK63, a transient inflammation occurred without permanent epithelial changes. Administration of three dose levels of the adjuvant in the presence of rRV caused no additional changes. LTK63 and LTR72 both were very effective and safe mucosal adjuvants at all three dose levels employed in these studies. Both significantly enhanced the protection of a marginally effective dose of rRV against aerosol delivered ricin challenge. LTK63 stimulated cytokines, which could be surrogate markers of efficacy, with human relevance potential. In spite of the better efficacy, rRV with LTK63, or with LTR72, failed to reduce the ricin-related lung injury. Most likely, a larger than suboptimal dose could resolve the lung injury of the vaccinated mice in the presence of a larger dose of the mucosal adjuvant. PMID- 17343961 TI - (238)U, (234)U, (226)Ra, (210)Po concentrations of bottled mineral waters in Italy and their dose contribution. AB - Due to the importance of bottled mineral water in human diet with special regard to children in lactation period, a monitoring of natural radioactivity in some bottled mineral waters produced in Italy was performed. Gross alpha and beta activities and (226)Ra, (238)U, (234)U, and (210)Po concentrations were measured. Gross alpha and beta activities were determined by standards ISO 9696 and ISO 9697; for (226)Ra determination liquid scintillation was used. The (238)U and (234)U concentrations were determined by alpha spectrometry after their separation from matrix by extraction chromatography and electroplating. (210)Po was measured by alpha spectrometry. The results revealed that the concentrations (mBqL(-1)) of (226)Ra, (238)U, (234)U, and (210)Po ranged from <10.00 to 52.50, from <0.17 to 89.00, from <0.17 to 79.00, and from <0.04 to 21.01, respectively. Uranium and radium concentrations do not reach the relevant recommended derived activity concentration (DWC). For polonium concentration, none of the samples reaches the relevant DWC in the case of adults and children, but one sample exceeds this value for infants. The dose contribution for different classes of age was calculated using the dose coefficient factors reported by EC Directive 96/29 EURATOM and certain annual intake. For children and adult age class, the calculated doses are quite similar and lower than 0.1mSvy(-1); for infants (<1y) in three cases the calculated dose ranges from 0.11 to 0.17mSvy(-1). PMID- 17343962 TI - Long-term investigations of radiocaesium activity concentrations in carp in North Croatia after the Chernobyl accident. AB - Long-term investigations of radiocaesium activity concentrations in carp in the Republic of Croatia are presented. The radiocaesium levels in carp decreased exponentially and the effective ecological half-life of (137)Cs was estimated to be about 1 year during 1987-2002 and 5 years during 1993-2005. The observed (134)Cs:(137)Cs activity ratio in carp was found to be similar to the ratio observed in other environmental samples. The concentration factor for carp (wet weight) was estimated to be 128+/-74 Lkg(-1), which is in reasonable agreement with model prediction based on K(+) concentrations in water. Estimated annual effective dose received by adult members of the Croatian population due to consumption of carp contaminated with (134)Cs and (137)Cs are small: per capita dose from this source during 1987-2005 was estimated to be 0.5+/-0.2 microSv. Due to minor freshwater fish consumption in Croatia and low radiocaesium activity concentrations in carp, it can be concluded that carp consumption was not a critical pathway for the transfer of radiocaesium from fallout to humans after the Chernobyl accident. PMID- 17343963 TI - Quality of life in the anxiety disorders: a meta-analytic review. AB - There has been significant interest in the impact of anxiety disorders on quality of life. In this meta-analytic review, we empirically evaluate differences in quality of life between patients with anxiety disorders and nonclinical controls. Thirty-two patient samples from 23 separate studies (N=2892) were included in the analysis. The results yielded a large effect size indicating poorer quality of life among anxiety disorder patients vs. controls and this effect was observed across all anxiety disorders. Compared to control samples, no anxiety disorder diagnosis was associated with significantly poorer overall quality of life than was any other anxiety disorder diagnosis. Examination of specific domains of QOL suggests that impairments may be particularly prominent among patients with post traumatic stress disorder. QOL domains of mental health and social functioning were associated with the highest levels of impairment among anxiety disorder patients. These findings are discussed in the context of future research on the assessment of quality of life in the anxiety disorders. PMID- 17343965 TI - Emotional deficits in psychopathy and sexual sadism: implications for violent and sadistic behavior. AB - While both psychopaths and sexual sadists engage in acts of predatory violence, little empirical work has examined the relationship between the two disorders. This paper outlines the constructs of psychopathy and sexual sadism and reviews the literature investigating the emotional lives of individuals with these disorders, paying particular attention to how emotional deficits might facilitate instrumental violence. Specifically, it is hypothesized that the emotion recognition and emotional experience deficits found among psychopaths, and perhaps present in sexual sadists, may lead to deficits in their ability to empathize with others, resulting in an increased likelihood for perpetrating instrumental violence. The relationship between empathy and aggression in psychopaths and sexual sadists is discussed, and distinctions are drawn between the two disorders with respect to their capacities to experience cognitive and affective empathy on a global level. Gaps in the literature are identified and additional areas of inquiry are suggested. PMID- 17343964 TI - Identifying mechanisms of treatment effects and recovery in rehabilitation of schizophrenia: longitudinal analytic methods. AB - The longitudinal dimension of schizophrenia and related severe mental illness is a key component of theoretical models of recovery. However, empirical longitudinal investigations have been underrepresented in the psychopathology of schizophrenia. Similarly, traditional approaches to longitudinal analysis of psychopathological data have had serious limitations. The utilization of modern longitudinal methods is necessary to capture the complexity of biopsychosocial models of treatment and recovery in schizophrenia. The present paper summarizes empirical data from traditional longitudinal research investigating recovery in symptoms, neurocognition, and social functioning. Studies conducted under treatment as usual conditions are compared to psychosocial intervention studies and potential treatment mechanisms of psychosocial interventions are discussed. Investigations of rehabilitation for schizophrenia using the longitudinal analytic strategies of growth curve and time series analysis are demonstrated. The respective advantages and disadvantages of these modern methods are highlighted. Their potential use for future research of treatment effects and recovery in schizophrenia is also discussed. PMID- 17343966 TI - The effect of Parkinson's disease on time estimation as a function of stimulus duration range and modality. AB - The present research sought to investigate the role of the basal ganglia in timing of sub- and supra-second intervals via an examination of the ability of people with Parkinson's disease (PD) to make temporal judgments in two ranges, 100-500 ms, and 1-5 s. Eighteen non-demented medicated patients with PD were compared with 14 matched controls on a duration-bisection task in which participants were required to discriminate auditory and visual signal durations within each time range. Results showed that patients with PD exhibited more variable duration judgments across both signal modality and duration range than controls, although closer analyses confirmed a timing deficit in the longer duration range only. The findings presented here suggest the bisection procedure may be a useful tool in identifying timing impairments in PD and, more generally, reaffirm the hypothesised role of the basal ganglia in temporal perception at the level of the attentionally mediated internal clock as well as memory retrieval and/or decision-making processes. PMID- 17343967 TI - Ziprasidone-induced acute laryngeal dystonia. PMID- 17343968 TI - Hazard characterisation in food allergen risk assessment: the application of statistical approaches and the use of clinical data. AB - A structured approach to assess the risk to allergic individuals from food allergens requires as a first step the experimental measurement of minimum eliciting doses in a population that is as representative as possible of the relevant allergic population, using a standardised protocol. These doses are established in controlled challenge studies, but logistical and statistical constraints mean that a proportion of the allergic population may still be at risk of reacting at doses below those which have been or could feasibly be tested. However, statistical modelling of the dose distribution resulting from such challenges permits inferences to be drawn about the proportion of allergic individuals that are likely to react to specified (low) amounts of residual allergen in food. However, different statistical models, which all provide good fits to the experimental data yield different values outside the experimental range. Consequently, the outputs from these models require a form of validation, which demonstrates how close the predictions are to reality. In addition to characterisation of the hazard, for each allergenic food this validation requires information about exposure to undeclared allergen, the actual number of reactions taking place in the wider allergic population, and the prevalence of allergy to that food. PMID- 17343969 TI - Risk and benefits from consuming salmon and trout: a Canadian perspective. AB - Recent reports on the presence of persistent organic chemicals in wild and farmed salmon have left consumers and health professionals confused regarding the safety of regular fish consumption. The objectives of this study were (1) to compare concentrations of key contaminants and the essential nutrients omega-3 fatty acids between farmed and wild salmon and trout, and (2) to balance risks and benefits from regularly consuming these species. Concentrations of mercury, polychlorinated biphenyls, dioxins and furans as well as omega-3 fatty acids were determined in fillets from farmed salmon and trout bought in various markets located in Quebec, Canada, as well as in fillets from wild salmonids obtained from fishermen and various Canadian agencies. While differences were observed between market (farmed) and wild fish with regard to the concentrations of mercury and polychlorinated biphenyls, overall the concentrations of contaminants were low, such that the regular consumption of these fish would not cause tolerable daily intakes to be exceeded. Our results indicate that salmon and trout sold in Quebec markets, which as in markets located elsewhere in North America originate for the most part from Chilean farms, can be consumed regularly to achieve optimal nutritional benefits from omega-3 fatty acids, without incurring significant contaminant related health risks. PMID- 17343970 TI - Study on developmental abnormalities in hypospadiac male rats induced by maternal exposure to di-n-butyl phthalate (DBP). AB - The objective of this study was to establish a hypospadiac rat model by maternal exposure to di-n-butyl phthalate (DBP) and to evaluate the developmental abnormalities of hypospadiac male rats. Timed-pregnant rats were given DBP by gastric intubation at doses of 0, 250, 500, 750 or 1000 mg/kg body weight (bw)/day from gestation day (GD) 14 to 18 to establish a hypospadiac rat model. The hypospadias was observed in the 500 and 750 mg/kg bw/day groups, the incidence of which was 6.8 and 41.3%, respectively. Transverse serial histological analysis of genitalia of hypospadiac male rats confirmed the malformation. With exposed dose increasing, the serum testosterone (T) levels of male rats inversely decreased, and in the same dosage group the serum T levels of hypospadiac rats were significantly lower than the levels of nonhypospadiac counterparts. The other reproductive lesions such as cryptorchidism and decreased ratio of anogenital distance/body weight (AGD/bw) were also observed. Autopsy analysis revealed the development of reproductive organs (prostate, testes, epididymis, pituitary gland) and nonreproductive organs (adrenal gland, liver, kidney, heart, spleen) of hypospadiac rats and nonhypospadiac counterparts. The results indicated that the reproductive system and developmental condition of hypospadiac male offspring were damaged severely by DBP. PMID- 17343972 TI - Laryngoscopic versus intubating LMA guided tracheal intubation by novice users--a manikin study. AB - AIM OF THE STUDY: Airway control is a potentially lifesaving procedure but tracheal intubation by direct laryngoscopy is difficult. This pilot study was conducted to determine whether tracheal intubation was more rapid and the success rate higher using an intubating laryngeal mask airway. MATERIAL AND METHODS: The success rates of 119 medical students without prior airway management experience in ventilating and then intubating the trachea of a Laerdal Airway Management Trainer with two different methods were compared. The methods were bag-mask ventilation (BM-V) followed by laryngoscopic intubation (LG-TI), and intubating laryngeal mask ventilation (ILMA-V) followed by ILMA-guided tracheal intubation (ILMA-TI). After an introductory lecture and demonstration, each student was allowed three attempts to intubate using each method in random order. RESULTS: All participants were successful with BM-V and ILMA-V on the first attempt. Laryngoscopic tracheal intubation was achieved by 60 (50.4%), 31 (26.1%) and 12 (10.1%) participants on the first, second and third attempt, respectively, while 16 (13.4%) failed in all three attempts. In the ILMA-TI group, 107 (90.0%), 10 (8.4%) and 2 (1.6%) succeeded on the first, second and third attempt, respectively. None failed. The intergroup difference is highly significant (p<0.001). Male participants were more successful with LG-TI than female (p<0.01), but not with ILMA-TI. CONCLUSION: Laryngoscopic orotracheal intubation is difficult for the untrained, but all participants were successful with ILMA TI. These data suggest that alternative devices such as the ILMA should be included in the medical school curriculum for airway management. PMID- 17343971 TI - PML and PML nuclear bodies: implications in antiviral defence. AB - The establishment of an intracellular antiviral state is the defining activity of interferons (IFNs) as well as the property that permitted their discovery. Several pathways have been implicated in resistance to viral infection in IFN treated cells, one of which implicates the ProMyelocytic Leukaemia (PML) protein and PML nuclear bodies (NBs, also known as ND10). PML NBs are dynamic intranuclear structures that require PML for their formation and which harbour numerous other transiently or permanently localised proteins. PML is expressed as a family of isoforms (PML I-VII) as a result of alternative splicing, most of which are found in the nucleus. IFN treatment directly induces transcription of the genes encoding both PML and Sp100, (another major component of PML NBs), resulting in higher levels of expression of these proteins and increases in both the size and number of PML NBs. These and other observations have encouraged the hypothesis that PML, PML NBs and a number of other constituents of these structures are involved in host antiviral defences. For example, exogenous expression of PML III or PML VI can impede infection by a number of RNA and DNA viruses, and certain viral proteins accumulate in PML NBs then cause their disruption by a variety of mechanisms. Although there are many other functions of PML NBs in a wide range of cellular pathways, there is accumulating evidence that they represent preferential targets for viral infections and that PML plays a role in the mechanism of the antiviral action of IFN. This article reviews the potential antiviral activities of PML NB constituent proteins, how RNA and DNA viruses overcome these defences, and the connections between these events and IFN pathways. PMID- 17343973 TI - Basic cardiopulmonary resuscitation skills of nurses at a teaching hospital in Southeast Iran in 2006. PMID- 17343974 TI - Associations between iris characteristics and personality in adulthood. AB - Variable and person-oriented analyses were used to explore the associations between personality and three previously untested general iris characteristics: crypts, pigment dots and contraction furrows. Personality data, as measured by the NEO PI-R and ratings of iris characteristics from 428 undergraduate students were collected. Crypts were significantly associated with five approach-related behaviors, i.e., feelings, tendermindedness, warmth, trust and positive emotions, whereas furrows were associated with impulsiveness. These findings suggest that because Pax6 induces tissue deficiencies in both the iris and the left anterior cingulate cortex, Pax6 may influence the extent people engage in approach-related behaviors. The results from using a person-oriented analysis suggested that people with different iris configurations tend to develop along different personality trajectories. Future longitudinal studies, twin-studies and genetic association studies, may benefit from collecting iris data and testing candidate genes for crypts and furrows. PMID- 17343975 TI - Response to "Anoscopy could be beneficial for women with external anogenital condyloma". PMID- 17343977 TI - Modelling the response of surface water quality to the urbanization in Xi'an, China. AB - The study investigated the response of surface water quality to urbanization in Xi'an, China. We qualitatively described the change in urban land use from 1996 to 2003, analyzed the status of the surface water environment, and constructed a model of urban expansion to simulate the water environment's response to urbanization. Our results revealed that patterns of land use changed dramatically, the rate of economic growth exceeded that of urbanization during the study period, and increasing urban land use was correlated with fluctuations in water quality. The simulated results suggested that urbanization had reached the environmental carrying capacity based on the average land utility and the marginal costs of pollution. PMID- 17343976 TI - The effect of retained embryos on pregnancy outcome in an in vitro fertilization and embryo transfer program. AB - OBJECTIVE: The purpose of this study was to determine the incidence of retained embryos and its impact on pregnancy outcome in the absence of known risk factors like blood and mucus in the transfer catheter. The factors that could be associated with embryo retention were also investigated. STUDY DESIGN: The results of all embryo transfer procedures performed at Ankara IVF Center between January 2003 and December 2005 were analyzed retrospectively. Three hundred and five embryo transfers, in which the transfer catheter was contaminated with blood or mucus, were excluded and the remaining 1,454 embryo transfers, with clean catheter, were enrolled into the study. Both fresh (n=1,422) and frozen (n=32) embryo transfers were included. RESULTS: The overall incidence of retained embryos during study period was 2.8% (41/1,454) following a clean initial embryo transfer. The mean age of the female partner, mean number of retrieved oocytes, MII oocytes, fertilized oocytes and the embryos transferred were similar in patients with and without retained embryos. The 1,454 embryo transfers performed during the study period resulted in 712 pregnancies (49%), of which 639 proved to be clinical pregnancies with a rate of 44%. The implantation rate was 22.8%. Pregnancy outcomes including positive beta-hCG (58.5% versus 48.7%), biochemical (4.7% versus 5.1%) and clinical pregnancy rates (53.6% versus 43.6%), implantation rate (24% versus 22.7%) and multiple pregnancy rate (36.3% versus 44.7%) were not significantly different between patients with and without retained embryos. An influence of individual physicians and embryologists on the frequency of retained embryos was not detected. The type of embryo transfer catheter used did not show any difference in terms of embryo retention. The cleavage stages of embryos were not different between groups. Although it was not statistically significant, the number of embryos transferred appeared to be a potentially confounding factor for retained embryos (p=0.053) and it might be significant in a slightly larger sample. When transfer of one or two embryos was compared to three or more embryos, the likelihood of retained embryos increased from 1.2% (4/321) to 3.2% (37/1,133). CONCLUSION: Retained embryos in the transfer catheter and immediate retransfer of them have no adverse impact on clinical pregnancy and implantation rates unless other previously reported signs of difficult transfer are also observed. PMID- 17343978 TI - Future directions for therapeutic ultrasound. PMID- 17343979 TI - Imaging local scatterer concentrations by the Nakagami statistical model. AB - The ultrasonic B-mode image is an important clinical tool used to examine the internal structures of the biological tissue. Due to the fact that the conventional B-scans cannot fully reflect the nature of the tissue, some useful quantitative parameters have been applied to quantify the properties of the tissue. Among various possibilities, the Nakagami parameter was demonstrated to have an outstanding ability to detect the variation of the scatterer concentration. This study is aimed to develop a scatterer concentration image based on the Nakagami parameter map to assist in the B-mode image for tissue characterization. In particular, computer simulations are carried out to generate phantoms of different scatterer concentrations and echogenicity coefficients and their B-mode and Nakagami parametric images are compared to evaluate the performance of the Nakagami image in differentiating the properties of the scatterers. The simulated results show that the B-mode image would be affected by the system settings and user operations, whereas the Nakagami parametric image provides a comparatively consistent image result when different diagnosticians use different dynamic ranges and system gains. This is largely because the Nakagami image formation is only based on the backscattered statistics of the ultrasonic signals in local tissues. Such an imaging principle allows the Nakagami image to quantify the local scatterer concentrations in the tissue and to extract the backscattering information from the regions of the weaker echoes that may be lost in the B-mode image. These findings suggest that the Nakagami image can be combined with the use of the B-mode image simultaneously to visualize the tissue structures and the scatterer properties for a better medical diagnosis. PMID- 17343980 TI - Finite amplitude measurements of the nonlinear parameter B/A for liquid mixtures spanning a range relevant to tissue harmonic mode. AB - The objective of this investigation was to measure the nonlinear parameter B/A using an enhanced finite amplitude distortion technique, based on nonlinear propagation effects analogous to those associated with tissue harmonic imaging. These measurements validate an improved method for measuring the nonlinear parameter B/A, the small-signal speed of sound, and the attenuation coefficient from a single set of ultrasonic measurements. To test the method, measurements were performed on 11 different mixtures of isopropyl alcohol (isopropanol) and water that span the range of concentrations from 0% to 100% isopropanol. Results for B/A ranging from approximately five to 11 were found to be reproducible and in good agreement with previously published values obtained using a thermodynamic method. PMID- 17343981 TI - Atorvastatin treatment for men with lower urinary tract symptoms and benign prostatic enlargement. AB - OBJECTIVE: To evaluate the effects of atorvastatin in men with lower urinary tract symptoms (LUTS) and prostatic enlargement due to presumed BPH. METHODS: This was a phase 2, double-blind, randomised, placebo-controlled clinical study. Eligible patients were aged > or =50 yr, with International Prostate Symptom Score (IPSS) > or = 13, total prostate volume (TPV) > or = 30 ml, and maximum urinary flow rate 5-15 ml/s. All patients had serum low-density lipoprotein (LDL) 100-190 mg/dl at baseline. Patients received either atorvastatin 80 mg daily (n=176) or placebo (n=174) for 26 wk. End points included IPSS, TPV, transition zone volume (TZV), maximum urinary flow rate (Q(max)), serum PSA, and lipids. RESULTS: There was no difference between the effects of atorvastatin and placebo on the primary end point of mean change from baseline in IPSS after 26 wk of double-blind treatment (-4.5 vs. -4.3; p=0.263). Similarly, no effect was seen on the lower urinary tract secondary end points including TPV (-1.6 vs. -1.9 ml; p=0.654), TZV (-0.0 vs. -0.8 ml; p=0.421), Q(max) (+1.1 vs. +0.7 ml/s; p=0.612), and PSA (-0.24 vs. -0.14 ng/ml; p=0.235). Atorvastatin had a significant effect on serum lipid levels compared with placebo (eg, LDL: -75.6 vs. -6.1 mg/dl; p<0.001). CONCLUSIONS: Atorvastatin is not effective over 6 mo in the treatment of men with LUTS and prostatic enlargement due to presumed BPH who have serum LDL in the range 100-190 mg/dl. PMID- 17343982 TI - Negative growth control of osteosarcoma cell by Bowman-Birk protease inhibitor from soybean; involvement of connexin 43. AB - Bowman-Birk protease inhibitor (BBI) from soybean acts as a potential chemopreventive agent in several types of tumors. However, the mechanism is still unclear. The present study was undertaken to estimate a mechanism of BBI dependent negative growth control of human osteosarcoma cell (U2OS cell). BBI had negative growth control of the cells via induction of connexin (Cx) 43, a tumor suppressor gene in U2OS cells. This negative growth control by BBI was abrogated under down-regulation of Cx43 induced by a Cx43 antisense nucleotide treatment. It was also found that the BBI-dependent induction of Cx43 was due to elevation of Cx43 mRNA and stabilization of Cx43 protein. Especially, BBI-dependent inhibition of chymotrypsin-like activity in proteasome contributed to stabilization of Cx43 protein. These results suggest that a major negative growth effect of BBI is based on the restoration of Cx43 expression in U2OS cells. PMID- 17343983 TI - Suppression of tumor-induced angiogenesis by Brazilian propolis: major component artepillin C inhibits in vitro tube formation and endothelial cell proliferation. AB - Propolis, a resinous substance collected by honeybees from various plant sources, possesses various physiological activities such as antitumor effects. We have previously shown that propolis of Brazilian origin was composed mainly of artepillin C and that its constituents were quite different from those of propolis of European origin. In this report, we examined an antiangiogenic effects of Brazilian propolis and investigated whether artepillin C was responsible for such effects. In an in vivo angiogenesis assay using ICR mice, we found that the ethanol extract of Brazilian propolis (EEBP) significantly reduced the number of newly formed vessels. EEBP also showed antiangiogenic effects in an in vitro tube formation assay. When compared with other constituents of EEBP, only artepillin C was found to significantly inhibit the tube formation of HUVECs in a concentration-dependent manner (3.13-50microg/ml). In addition, artepillin C significantly suppressed the proliferation of HUVECs in a concentration-dependent manner (3.13-50microg/ml). Furthermore, artepillin C significantly reduced the number of newly formed vessels in an in vivo angiogenesis assay. Judging from its antiangiogenic activity in vitro and in vivo, we concluded that artepillin C at least in part is responsible for the antiangiogenic activity of EEBP in vivo. Artepillin C may prove useful in the development of agents and foods with therapeutic or preventive activity against tumor angiogenesis. PMID- 17343984 TI - Effect of Pb toxicity on root morphology, physiology and ultrastructure in the two ecotypes of Elsholtzia argyi. AB - Seed germination and hydroponics experiments were conducted to underpin the effects of Pb on mined ecotype (ME) and non-mined ecotype (NME) of Elsholtzia argyi from Pb/Cu mining areas and the non-contaminated agricultural areas, respectively. In both experiments, ME exhibited higher tolerance to excessive levels of Pb in the growth medium. Various Pb treatments caused a stimulatory effect on seed germination of both the ecotypes. Concentrations of Pb in the leaves and the stem of the ME were 2.6 and 4.5 times respectively higher than those of the NME when plants were supplied with Pb level of 200microM. Pb posed adverse effects on root morphological organization and root activity of both the ecotypes but decrease was not sharp and root activity was recovered in ME plants. Root ultrastructural studies revealed that in ME, Pb was detected as fine particles dispersed throughout the cell membrane and cell wall fraction, whereas most of the Pb was found as large aggregates deposited in the cell walls of NME plants. Comparatively better growth, higher tolerance and accumulation of Pb expressed by ME plants is mainly attributed to the maintenance of its root growth and activity as well as integrity of cell organelles. PMID- 17343985 TI - Protein glycosylation in pmt mutants of Saccharomyces cerevisiae. Influence of heterologously expressed cellobiohydrolase II of Trichoderma reesei and elevated levels of GDP-mannose and cis-prenyltransferase activity. AB - Protein O-mannosylation has been postulated to be critical for production and secretion of glycoproteins in fungi. Therefore, understanding the regulation of this process and the influence of heterologous expression of glycoproteins on the activity of enzymes engaged in O-glycosylation are of considerable interest. In this study we expressed cellobiohydrolase II (CBHII) of T. reesei, which is normally highly O-mannosylated, in Saccharomyces cerevisiae pmt mutants partially blocked in O-mannosylation. We found that the lack of Pmt1 or Pmt2 protein O mannosyltransferase activity limited the glycosylation of CBHII, but it did not affect its secretion. The S. cerevisiae pmt1Delta and pmt2Delta mutants expressing T. reesei cbh2 gene showed a decrease of GDP-mannose level and a very high activity of cis-prenyltransferase compared to untransformed strains. On the other hand, elevation of cis-prenyltransferase activity by overexpression of the S. cerevisiae RER2 gene in these mutants led to an increase of dolichyl phosphate mannose synthase activity, but it did not influence the activity of O mannosyltransferases. Overexpression of the MPG1 gene increased the level of GDP mannose and stimulated the activity of mannosyltransferases elongating O-linked sugar chains, leading to partial restoration of CBHII glycosylation. PMID- 17343986 TI - Novel therapeutic approaches in the treatment of advanced pancreatic carcinoma. AB - Pancreatic cancer is still a malignant disease of grim prognosis despite all therapeutic efforts. Because clinical symptoms in the early stage are usually absent or aspecific, it is frequently discovered at advanced or metastatic stage, only around 15-20% of tumors are resectable. In the majority of patients only the chemotherapy offers a prolongation of life, but even the first-line chemotherapeutic agent, the gemcitabine has a modest survival benefit, and objective tumor response is rarely achieved. Combination of various cytostatics did not produce a significant improvement either. For that reason, continuous search for other agents is mandatory. Nowadays, in the era of molecular-targeted oncotherapeutic approaches, pancreatic cancer is also a subject such trials: epidermal growth factor receptor blockade, inhibition of angiogenesis, modulation of tumor response through the extracellular matrix, inhibition of cyclooxygenase 2, farnesyl transferase inhibitors, signal transduction inhibitors, ablation of the hormonal influence and some other aspects have all been studies, but to date, no breakthrough in the treatment of pancreatic carcinoma is proven. In several Phase II-III studies these compounds given alone displayed marginal effects, but when combined with the standard cytostatics, some beneficial effects were observed, however, some of them displayed a severe (sometimes fatal) toxicity. To date, the role of the molecular targeted therapy in pancreatic carcinoma is promising, but the results are not convincingly superior to the standard chemotherapeutic treatments. Pancreatic adenocarcinoma remains a great challenge for the oncologists, and continuous search for better molecules and/or combinations is inevitable. PMID- 17343987 TI - Inhibition of cyclin-dependent kinases is neuroprotective in 1-methyl-4 phenylpyridinium-induced apoptosis in neurons. AB - The biochemical pathways involved in neuronal cell death in Parkinson's disease are not completely characterized. Mitochondrial dysfunction, specifically alteration of the mitochondrial complex I, is the primary target of the parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP+) induced apoptosis in neurons. In the present study, we examine the role of caspase-dependent and independent routes in MPP+-induced apoptosis in rat cerebellar granule neurons (CGNs). We show a distinct increase in the expression of the cell cycle proteins cyclin D, cyclin E, cdk2, cdk4 and the transcription factor E2F-1 following a MPP+ treatment of CGNs. Flavopiridol (FLAV), a broad inhibitor of cyclin dependent kinases (CDKs), attenuated the neurotoxic effects of MPP+ and significantly attenuates apoptosis mediated by MPP+ 200 microM. Likewise, the antioxidant vitamin E (vit E) increases neuronal cell viability and attenuates apoptosis induced by MPP+. Moreover, the expression levels of cyclin D and E2F-1 induced by this parkinsonian neurotoxin were also attenuated by vit E. Since, the broad-spectrum caspase inhibitor zVAD-fmk did not attenuate MPP+-induced apoptosis in CGNs, our data provide a caspase-independent mechanism mediated by neuronal reentry in the cell cycle and increased expression of the pro-apoptotic transcription factor E2F-1. Our results also suggest a potential role of oxidative stress in neuronal reentry in the cell cycle mediated by MPP+. Finally, our data further support the therapeutic potential of flavopiridol, for the treatment of Parkinson's disease. PMID- 17343988 TI - Coronary hemodynamics and atherosclerotic wall stiffness: a vicious cycle. AB - Local hemodynamic environment, including low shear stress and increased tensile stress, determines the localization, growth and progression of coronary atherosclerosis. As atherosclerotic lesions evolve, the diseased coronary arteries undergo local quantitative and qualitative changes in their wall, and progressively become stiff. Arterial stiffening amplifies the atherogenic local hemodynamic environment, initiating a self-perpetuating vicious cycle, which drives the progression of atherosclerosis and the formation of atherosclerotic plaque. In vivo evidence indicates that endothelial dysfunction is associated with arterial stiffness, an association that creates a challenging perspective of utilizing stiffness as an early marker of endothelial dysfunction and future atherosclerosis. Coronary stiffening is also associated with vascular remodeling, which is a major determinant of the natural history of atherosclerotic plaques. Thus, arterial stiffness may constitute a useful marker for the identification of the remodeling pattern, in particular expansive remodeling, which is closely associated with high-risk plaques. The early identification of endothelial dysfunction, or a high-risk plaque may enable the early adoption of preventive measures to improve endothelial function, or justify pre-emptive local interventions in high-risk regions to prevent future acute coronary syndromes. Further experimental and perspective clinical studies are needed for the investigation of these perspectives, whereas the development of new modalities for non-invasive and reliable assessment of coronary stiffness is anticipated to serve these studies. PMID- 17343989 TI - Cardiovascular effects of Hyptis fruticosa essential oil in rats. AB - In non-anesthetized normotensive rats, Hyptis fruticosa essential oil (HFEO, 5, 10, 20 and 40 mg/kg; i.v.) induced hypotension associated with tachycardia. In intact and isolated rings of rat superior mesenteric artery (control), HFEO (1 1000 microg/ml, n=6, cumulatively) induced concentration-dependent relaxations of tonus induced by 10 microM phenylephrine (Phe) (pD(2)=2.6+/-0.27; E(max)=64+/ 8.3%). In denuded endothelium pre-contracted rings with Phe or K(+)-depolarizing solution (80 mM), the concentration-response curves to HFEO were not shifted (pD(2)=2.3+/-0.25 and 2.3+/-0.28, respectively), but their maximal responses were significantly (P<0.05 vs control) increased (E(max)=122.3+/-18.2% and 92+/-3.6%, respectively). HFEO was also capable of antagonizing the concentration-response curves to CaCl(2) (3 microM-30 mM) in a dose-dependent manner. PMID- 17343990 TI - Millaurine A, a new guanidine alkaloid from seeds of Millettia laurentii. AB - A new guanidine alkaloid, millaurine A (1), was isolated from the methanol extract of the seeds of Millettia laurentii. The structure of the new compound was elucidated on the basis of spectral analysis. PMID- 17343991 TI - Isolation of six isoflavones from Semen sojae praeparatum by preparative HPLC. AB - A method for the isolation of six isoflavones (genistein, genistin, daidzein, daidzin, glycitein and glycitin) with high purity from Semen sojae praeparatum, a famous traditional Chinese medicine, by preparative HPLC is described. PMID- 17343992 TI - Sesquiterpenes from Ulmus davidiana var. japonica with the inhibitory effects on lipopolysaccharide-induced nitric oxide production. AB - Investigation of antiinflammatory constituents of the stem and root barks of Ulmus davidiana var. japonica resulted in the isolation of three guaiane type sesquiterpenes, torilin, 1-hydroxytorilin, together with a new derivative, (1beta, 7beta, 8beta, 10beta)-1,8,11-trihydroxy-4-guaien-8-angeloyl-3-one named 1 hydroxytorilin A. All the three sesquiterpenes inhibited lipopolysaccharide induced nitric oxide production in murine microglial BV2 cells. PMID- 17343993 TI - Do rats time filled and empty intervals of equal duration differently? AB - The goal was to determine whether rats time filled and empty intervals of equal duration differently. Each of five rats was trained for 50 sessions on an instrumental appetitive head entry procedure in which food was available (primed) every 120 s. On "empty" cycles, 30s prior to the next food prime, a 0.5-s pulse of white noise was presented. On "filled" cycles, 30s prior to the next food prime, white noise came on and stayed on until food was delivered. The two types of cycles were presented with equal probability. The results showed that the rats timed both the food-to-food interval and the stimulus-to-food interval. A comparison of the response gradients on filled and empty cycles following stimulus presentation showed better temporal discrimination on filled cycles. The results were modeled using a Packet theory of timing, with a linear averaging rule to combine the temporal information provided by the stimulus and food. The model fits to the individual response gradients were evaluated with a Turing test. PMID- 17343994 TI - Species differences between rats and pigeons in choices with probabilistic and delayed reinforcers. AB - An adjusting-delay procedure was used to study rats' choices with probabilistic and delayed reinforcers, and to compare them with previous results from pigeons. A left lever press led to a 5-s delay signaled by a light and a tone, followed by a food pellet on 50% of the trials. A right lever press led to an adjusting delay signaled by a light followed by a food pellet on 100% of the trials. In some conditions, the light and tone for the probabilistic reinforcer were present only on trials that delivered food. In other conditions, the light and tone were present on all trials that the left lever was chosen. Similar studies with pigeons [Mazur, J.E., 1989. Theories of probabilistic reinforcement. J. Exp. Anal. Behav. 51, 87-99; Mazur, J.E., 1991. Conditioned reinforcement and choice with delayed and uncertain primary reinforcers. J. Exp. Anal. Behav. 63, 139-150] found that choice of the probabilistic reinforcer increased dramatically when the delay-interval stimuli were omitted on no-food trials, but this study found no such effect with the rats. In other conditions, the probability of food was varied, and comparisons to previous studies with pigeons indicated that rats showed greater sensitivity to decreasing reinforcer probabilities. The results support the hypothesis that rats' choices in these situations depend on the total time between a choice response and a reinforcer, whereas pigeons' choices are strongly influenced by the presence of delay-interval stimuli. PMID- 17343995 TI - Characterization of the promoter of the gene encoding human tripeptidyl-peptidase II and identification of upstream silencer elements. AB - Tripeptidyl-peptidase II (TPP II) is one of the many proteases involved in the important process of intracellular proteolysis. The widespread distribution and broad substrate specificity suggest that TPP II is encoded by a "house-keeping gene". However, both TPP II protein and mRNA levels vary in different cells. To investigate whether these variations are due to regulation on a genetic level, the promoter of the TPP2 gene has previously been identified. The promoter contains two inverted CCAAT-boxes and an E-box. By means of reporter assays and electrophoretic mobility shift assays the promoter has now been further characterized. It could be concluded that USF-1 (upstream stimulatory factor-1) binds to the E-box in the promoter. The transcription factors NF-Y and USF-1 are present in protein-DNA complexes of different sizes. Mutation of the E-box had no effect, indicating that only binding of NF-Y to the two CCAAT-boxes was important for activation of transcription. However, this does not exclude the possibility that USF-1 can play an important role in transcription in other types of cells. Furthermore, the region upstream of the promoter was investigated due to its ability to inhibit transcription. Several silencer elements were identified and we also showed that Oct-1 binds to one of these elements. Thus, this investigation reveals that TPP II expression could be regulated through both positive and negative regulatory elements. Further studies are required to establish the involvement of different genetic elements, and how the interplay between different transcription factors will affect the transcriptional rate in vivo. PMID- 17343996 TI - Heterochromatin protein 1 interacts with 5'UTR of transposable element ZAM in a sequence-specific fashion. AB - The realization of cross talks between transposable elements of class I and their host genome involves non-histonic chromatin proteins. These interactions have been widely analyzed through the characterization of the gypsy retrotransposon leader region, which holds a particularly strong insulator element, and the proteins required for its function, Su(Hw), Mod(mdg4), and Cp190. Here we provide evidence that a similar interaction should occur between ZAM, a gypsy-like element, and HP1, one of the most extensively studied chromatin proteins. We first assayed the existence of this binding using the yeast cells one-hybrid system and then we verified it in vivo by ChIP assay. In order to characterize the interaction between HP1 and the ZAM 5' untranslated region we performed a series of gel shift analyses. Our observations confirm an HP1 co-operative DNA binding and display for the first time the HP1 DNA target motif that, we hypothesize, should be one of its nucleation sites. PMID- 17343998 TI - Alcohol dehydrogenase and catalase content in perinatal infant and adult livers: potential influence on neonatal alcohol metabolism. AB - Methanol and ethanol are primarily metabolized through the alcohol dehydrogenase (ADH) system in adults. Under saturating substrate concentrations, blood alcohol concentrations decline at a constant rate (i.e., zero-order kinetics). Minor metabolic alcohol pathways include oxidation through the cytochrome P450 system and catalase. We previously reported a 5-week-old infant that survived intoxication at an exceptional methanol concentration (1148 mg/dL). As the rate of elimination followed first-order kinetics, we proposed that an alternate non saturating alcohol metabolizing enzyme system such as catalase was responsible for this observation. In this study, we developed and optimized enzyme immunoassays for tissue ADH and catalase, and measured the concentration of these enzymes in the livers of 18 adults and 7 perinatal infants obtained from autopsies. The mean ADH content of perinatal infants was approximately 10-fold lower than adults (0.11+/-0.09 g/kg versus 1.00+/-0.37 g/kg liver wet weight, respectively). The alphaalpha isoenzyme of ADH was the predominant isoform in perinatal infants, while there were several isoenzymes found in adult livers. For catalase, half of the perinatal infants (n=4) had roughly equal amounts as adults (0.32+/-0.03 g/kg versus 0.37+/-0.20 g/kg wet weight, p=NS), while three other perinatal infants had significantly higher concentrations (1.55+/-0.48 g/kg versus 0.37+/-0.02 g/kg wet weight, p<0.05). In the perinatal infants, these results suggest that catalase may play a more prominent role in the metabolism of alcohols than does the ADH system and may explain the finding of first-order kinetics in case reports of high methanol and ethanol intoxication. PMID- 17343997 TI - Krox20 is down-regulated following triazole in vitro embryonic exposure: a polycompetitor-based assay. AB - This study was conducted in order to analyse gene-expression alterations in rat embryos following exposure to triazoles, using an easy-handling approach. Triazole derivatives have been shown to alter the morphology of cranio-facial structures and to induce abnormalities in hindbrain patterning and neural crest cell migration. Specification of hindbrain segments is regulated by retinoic acid and the hox code. Krox20 was chosen as molecular marker for its specific distribution in the anterior neural tube. In fact, this zinc-finger protein is expressed in rhombomere 3 and 5. Mis-regulation of Krox20 levels have shown to induce severe alterations in the correct patterning of the rhomboencephalon and the derived structures. In order to analyse Krox20 mRNA levels in rat embryos exposed in vitro to the triazole derivative triadimefon, a semi-quantitative approach utilising the competitive RT-PCR was chosen. A lambda phage-based plasmid construct that could compete with target and internal standard gene at the same time during enzymatic reaction was generated. Results were confirmed by real-time RT-PCR analysis on the same samples. Our data show a down-regulation of Krox20 transcript levels after exposure to the triazole derivative, implying a key role of this molecule in the pathogenic pathway induced by triazole exposure. PMID- 17343999 TI - Development and validation of dissolution test for ritonavir soft gelatin capsules based on in vivo data. AB - The purpose of the study was to develop and validate a dissolution procedure for ritonavir soft gelatin capsules (Norvir) based on in vivo data. Several conditions such as medium composition, pH, surfactant concentration and rotation speed were evaluated. The method was carried out using the same batch of Norvir used in a bioequivalence study and the in vivo data were used to select the best dissolution test conditions based on in vitro-in vivo correlation (IVIVC). The dissolution test was validated using a high-performance liquid chromatographic method (HPLC). For this formulation, the best dissolution conditions were achieved using paddle, 900ml of medium containing water with 0.7% (w/v) of sodium lauryl sulfate at a rotation speed of 25rpm. Under these conditions a significant linear relationship between fraction of ritonavir absorbed and dissolved was obtained (R(2)=0.993) and a level A IVIVC was established. In the HPLC method a relative standard deviation for intra-day precision was <1.6% and for inter-day precision was <1.4%. Accuracy was from 98.5% to 101.6% over the concentration range required for the dissolution test (4.0-124.0microg/ml). Both the HPLC method and the dissolution test are validated and could be used to evaluate the dissolution profile of ritonavir soft gelatin capsules. PMID- 17344000 TI - Biocompatible, biodegradable and sterically stabilized phospholipid nanomicelles improve cryopreservation of oral keratinocytes: a preliminary investigation. AB - In this proof-of principle study, we determined whether biocompatible, biodegradable and sterically stabilized phospholipid nanomicelles (SSNMs) improve viability and membrane integrity of cryopreserved oral keratinocytes. Cultured chemically transformed hamster oral keratinocytes were frozen gradually with and stored in liquid nitrogen in the presence of 10% dimethylsulfoxide (DMSO) or SSNMs composed of distearoylphosphatidyl-ethanolamine-N-poly(ethylene glycol) 2000 (size, 17+/-1nm; 0.1 and 1.0nmol). Forty-eight hours later, cells were thawed and their viability was determined. Lactate dehydrogenase (LDH) activity in cell lysates and supernatants was quantified as well. SSNMs evoked a significant, concentration-dependant increase in cell viability in comparison to 10% DMSO (p<0.05). There was also a significant decrease in LDH activity in the supernatant of cells cryopreserved with SSNMs in comparison to 10% DMSO (p<0.05). These data indicate that SSNMs improve cryopreservation of oral keratinocyte by promoting cell viability and plasma membrane integrity. We suggest that SSNMs should be further developed as a novel nanocryopreservative for keratinocytes. PMID- 17344001 TI - Electrophysiologic correlates of intensity discrimination in cortical evoked potentials of younger and older adults. AB - When measured behaviorally, older adults with normal hearing have poorer intensity discrimination thresholds than younger adults, but only at lower frequencies. Poor intensity discrimination at lower but not higher frequencies for older adults can be associated with an age-related decline in temporal processing. The current study was designed to assess age-related effects on intensity discrimination at 500 and 3000 Hz using the cortical auditory evoked potential, N1--P2. Subjects were 10 younger and 10 older adults with normal hearing. The N1--P2 was elicited by an intensity increase in an otherwise continuous pure tone presented at 70 dB SPL. Intensity increments ranged from 0 dB to 5 dB at 500 Hz and from 0 d B to 8 d B at 3000 Hz in 1-dB steps. Intensity discrimination threshold was defined as the smallest intensity change needed to evoke an N1-P2 response. Consistent with behavioral measures, N1-P2 response thresholds were significantly higher for older subjects than younger subjects at 500 Hz but did not differ significantly at 3000 Hz. In addition, N1 and P2 latencies for older subjects were significantly prolonged at 500 Hz, but not at 3000 Hz. As intensity increments increased above threshold, amplitudes tended to be larger in older than in younger subjects, however, these differences were not statistically significant. In older subjects, response latencies and amplitudes were significantly larger at 500 Hz than at 3000 Hz. In younger subjects, response latencies and amplitudes were similar across frequency. Similar intensity discrimination thresholds and age-related differences for behavioral measures and evoked potentials support the notion that the N1-P2 measures reflect the physiological detection of intensity change which in turn relates to intensity discrimination. A possible explanation for the decreased intensity discrimination at low frequencies, and enhanced amplitudes with prolonged latencies in older subjects is an age-related decline in inhibitory control within the central auditory nervous system. PMID- 17344002 TI - Auditory associative memory and representational plasticity in the primary auditory cortex. AB - Historically, the primary auditory cortex has been largely ignored as a substrate of auditory memory, perhaps because studies of associative learning could not reveal the plasticity of receptive fields (RFs). The use of a unified experimental design, in which RFs are obtained before and after standard training (e.g., classical and instrumental conditioning) revealed associative representational plasticity, characterized by facilitation of responses to tonal conditioned stimuli (CSs) at the expense of other frequencies, producing CS specific tuning shifts. Associative representational plasticity (ARP) possesses the major attributes of associative memory: it is highly specific, discriminative, rapidly acquired, consolidates over hours and days and can be retained indefinitely. The nucleus basalis cholinergic system is sufficient both for the induction of ARP and for the induction of specific auditory memory, including control of the amount of remembered acoustic details. Extant controversies regarding the form, function and neural substrates of ARP appear largely to reflect different assumptions, which are explicitly discussed. The view that the forms of plasticity are task dependent is supported by ongoing studies in which auditory learning involves CS-specific decreases in threshold or bandwidth without affecting frequency tuning. Future research needs to focus on the factors that determine ARP and their functions in hearing and in auditory memory. PMID- 17344003 TI - Lateral medullary syndrome in a woman after ovulation induction. AB - Although atherothrombotic complications due to ovulation induction are well known in the literature, there is no previous report specifically on the presentation of a lateral medullary infarction. Recently, we have encountered a 36 years old woman with primary infertility having acute vertiginous attack after ovulation induction. Audiovestibular test battery revealed bilateral normal hearing, bilateral gaze nystagmus, rebound nystagmus beating toward the right side, loss of visual suppression with augmentation of caloric nystagmus in light on the left side, and delayed vestibular evoked myogenic potentials on the left side, which was subsequently confirmed as lateral medullary syndrome by MRI scan. In this patient, polycystic ovary syndrome plus high levels of follicle stimulating hormone (FSH) and estrogen, together with S protein deficiency may precipitate the occurrence of lateral medullary infarct after ovulation induction. Thus, in vitro fertilization treatment protocol has been terminated. PMID- 17344004 TI - B cells and aging: balancing the homeostatic equation. AB - The interplay of selective and homeostatic processes dominates the behavior of B lineage subsets following B cell antigen receptor (BCR) expression, and extends to determinants of immune response quality and the persistence of immunologic memory. A key concept emerging from these considerations is that primary events acting upstream of mature B lymphocyte pools can profoundly impact downstream populations as the system attempts homeostatic adjustments. Since, advancing age is accompanied by profound changes in B cell generation and homeostasis, establishing the relative contributions of primary lesions versus compensatory homeostatic processes is critical to understanding these perturbations. Exploration of this problem requires an understanding of: (1) the identity, dynamics, and progenitor/successor relationships of marrow and peripheral B cell subsets; (2) the nature and interactions of selective and homeostatic processes acting in these subsets; (3) how these change with age. Our data show that BLyS and its receptors mediate peripheral B cell homeostasis, and that the size, dynamics and behavior of all B cell subsets influenced by B Lymphocyte Stimulator change with age. These findings suggest that homeostatic processes mediated through B Lymphocyte Stimulator are altered with age, and that these perturbations may primarily reflect compensatory homeostatic adjustments to upstream reductions in B cell generation. PMID- 17344005 TI - A shift in the diagnostics of the small intestine tumors. AB - Primary, secondary, benign or malignant tumorous diseases of the small intestine are rare. They are very often diagnosed by accident or as a cause of acute abdomen. This work should answer the question, whether there is a method of making the diagnosis earlier when the disease is limited and easy to cure. METHODOLOGY: A retrospective study comprising 96 patients having undergone surgery for a small intestine tumor in our hospital from 1996 to 2005 is presented. An analysis of first symptoms, diagnostic methods and number of patients admitted during the years was made. In the year 1998 we changed our philosophy in trying to directly detect the small intestine pathology and not making the diagnosis by the exclusion only. Intestinal ultrasound was performed on the Ultramark 3000 HDI device with autofocussable convex 5 MHz and linear 7.5 MHz probes or nowadays ATL 5000 HDI, 7-12 MHz linear probe. No contrast enhancement was used. Abdominal CT engaged Somatom Plus appliance by Siemens, single detector with our conventional abdominal CT protocol. Enteroclysis was done with Micropaque suspension diluted 1:1 with HP-7000 300 ml with its application rate of 75 ml/min followed by HP-7000 solution 2000 ml, application rate of 120 ml/min. RESULTS: We treated surgically 96 patients with the small intestine tumor. A shift in the diagnostic algorithm was noticed in the bowel ultrasound now taking the lead. An enlarged portion of patients diagnosed by means of capsule endoscopy was also seen. An increase of surgically treated patients after 1998 was recorded and the majority of them could be offered an elective laparoscopic surgery in contrast to before 1998 when the majority of them had undergone surgery for an acute abdomen. CONCLUSION: The small bowel ultrasound can be recommended as the first choice method. All patients with even very moderate abdominal symptoms ought to be examined for the small intestine pathology. As a result one can get higher rate of elective surgery, if possible laparoscopic and higher number of R0 resections accompanied by longer survival. PMID- 17344006 TI - Amyloidosis of the small intestine. AB - Amyloidosis is a rare disease characterized by forming pathological protein deposits - amyloid - in many organs and tissues. This decreases their functionality. The aim of this small study was to determine, whether the radiological picture of the small intestine involvement in amyloidosis is in some sense specific as sometimes described in literature giving rise to high suspicion for the disease in symptomatic patients. MATERIAL AND METHODS: The prospective study comprising seven patients hospitalized in surgical department is presented together with a survey on the disease, its appearance in radiological imaging. All patients underwent abdominal ultrasound (ATL 5000 HDI, 7-12MHz linear probe, no contrast enhancement, supine position), abdominal CT (Somatom Plus, Siemens, single detector, conventional abdominal CT protocol) and enteroclysis (Micropaque suspension 300ml, application rate of 75ml/min, dilution with HP-7000 being 1:1 and HP-7000 solution 2000ml, application rate of 120ml/min.). RESULTS: The amyloid deposits in the small intestine could be visualized in five of seven patients with the disease. Enteroclysis revealed a diffuse slowed down intestinal motility with an obstruction-like picture in all of our seven patients. The intestinal secretion was normal, plicae were getting polyp-like shape in five of them forming so called "thumb printing" picture. CT showed thickening of the intestinal wall due to deposits with poor blood supply and contrast retention in five of seven patients. Ultrasound visualized thickened, hypoechoic nodular plicae and slowed down motility in these five patients. The most striking finding was the pathological deposits in the intestinal wall were highly hypo-vascular. However, this picture is very similar to that of ischemic enteritis. All seven patients had proven amyloid deposits from bioptic specimens. CONCLUSION: The diagnosis of amyloidosis must be supported by bioptic examination as it has no pathognomic radiological picture. Nevertheless, it allows usually to rise a high suspicion for this and sometimes even guess the type of the pathological protein involved. This can start a search for the primary reason of possible amyloidosis and thus perhaps spear the patients quality of life. PMID- 17344007 TI - The role of CT and endoscopic ultrasound in pre-operative staging of pancreatic cancer. AB - PURPOSE: The aim of our study was to compare the accuracy of computed tomography and endoscopic ultrasound (EUS) in pre-operative staging of pancreatic cancer. METHODS: Comparative retrospective study of 86 patients with pancreatic cancer. CT was done in 55 patients, 41 patients were examined by EUS. Each patient underwent surgery and had proven pancreatic cancer by histology. CT and EUS results were correlated to per-operative and histological findings. The main attention was paid to the description of peri-pancreatic lymphadenopathy, para aortic lymphadenopathy, peri-coeliac lymphadenopathy and tumor relationship to superior mesenteric vein, superior mesenteric artery, portal vein, inferior caval vein and common hepatic artery. A description rate was defined as number of pre operative findings where the structures and relationships mentioned above were described. RESULTS: The description rates of peri-pancreatic lymph nodes were 11 (20%) at CT and 36 (88.0%) at EUS. Para-aortic lymphadenopathy was described in 9 (16.0%) cases at CT and none at EUS. Peri-coeliac lymphadenopathy was mentioned only one time (2.0%) at CT contrary to 12 (29.0%) at EUS. Relationship of the tumor to the mesenteric vessels was well depicted in nine (16.0%) at CT versus nine (22.0%) at EUS. Portal vein relationship was well described in two (4.0%) at CT and seven (17%) cases at EUS. This description rate in vena cava inferior was one (2%) at CT and three (7.0%) at EUS, in hepatic artery it was one (2%) at CT and six (15%) at EUS. In the group of CT, resectability or non-resectability were well predicted in 33 (60%) patients and wrong predicted in 22 (40%) patients. In the group of EUS, resectability or non-resectability were well predicted in 34 (83%) patients and wrong predicted in 7 (17%) patients. CONCLUSION: According to our study, EUS is more accurate in prediction of local PC resectability than CT. PMID- 17344008 TI - Brachytherapy and percutaneous stenting in the treatment of cholangiocarcinoma: a prospective randomised study. AB - PURPOSE: To evaluate the effect of radiation therapy including intraluminal brachytherapy with iridium-192 on survival of patients with malignant biliary strictures (cholangiocarcinoma, histologically improved) treated with metallic stent in a prospective randomised study. METHOD AND MATERIALS: In the prospective randomised study, 21 patients with cholangiocarcinoma were treated with implantation of percutaneous stents followed with intraluminal Ir-192 brachytherapy (mean dose 30 Gy) and external radiotherapy (mean dose 50 Gy) and 21 patients were treated only with stents insertion. We did not find any statistically significant differences in age and tumor localization between these two groups of patients. RESULTS: All the patients died. In the group of patients treated with brachytherapy and with stent implantation, the mean survival time was 387.9 days. In the group of patients treated only with stent insertion the mean survival was 298 days. In effort to eliminate possible effect of external radiotherapy we treated the control group of eight patients with cholangiocarcinoma by stent insertion and brachytherapy only. CONCLUSION: Our results show that combined radiation therapy could extend the survival in the patients with cholangiocarcinoma obstruction. PMID- 17344009 TI - Analysis of the Spanish-speaking mailing list RADIOLOGIA. AB - The objective of this study was to analyse the mailing list RADIOLOGIA during its first 5 years of operation (from 1998 to 2003). A survey questionnaire was sent to evaluate the characteristics of subscribers and to score (from 0 to 9) the functionality, usefulness and quality of the mailing list. All messages sent to the list during the evaluated period were classified and quantified. A social network analysis was performed from all messages replied to during 2001 and 2002 with the option "reply to" included in the subject. One hundred and forty (36.8%) responses were collected from 380 subscribers, mainly radiologists (90.0%). 80% of responders were located in Spain, 16% in Latin America, and 4% in other places. The obtained scores (mean+/-standard deviation) were: functionality 7.4+/ 1.3; usefulness 7.0+/-1.4; and quality of e-mail contents 6.0+/-1.4. During the evaluated period 2700 e-mail messages were sent to the list, with a monthly distribution of 44.3+/-26.0. The list functioning has been based on an active minority of subscribers that provided information and responses to the rest of the subscribers, a ring of active members that participated in discussions, and about 50% of passive members. PMID- 17344010 TI - US and MR imaging of the postoperative knee. AB - Constantly increasing number of surgical procedures on the soft tissues of and around the knee generates the need for postoperative soft tissue assessment. Sports medicine is constantly seeking new--faster, better, more efficient--ways to help patients, especially competitive athletes to come back to their full activity as soon as possible. One of the important factors in that acceleration is postoperative tissue assessment. It helps the clinician making better decisions in terms of the rehabilitation stages, come back to basic and sport specific training and finally in letting the patient put a full load on the operated structure. The healing of the collagen structure cannot only be guided by patient's pain. Diagnostic imaging methods such as US and MRI, which focus on the soft tissue assessment are best fitted to do the job. They also help in the diagnostics of the reinjuries of operated structures. Often criteria used for basic diagnostics do not fit the need of assessment of the structure which underwent an initial injury, was operated, healed and often reinjured again. Criteria used for regular injury diagnostics are in most cases seriously modified. Moreover the whole matter of structure evaluation after an injury and medical intervention leaves a lot of slippery ground and should be carefully studied before taking the challenge of judging the surgeon and the natural healing processes. Diagnostic judgment has much more impact on the operated patient than the primary injury diagnosis. Depending on the author both MRI and US are pointed out as the best imaging methods in terms of postoperative knee assessment. In fact both methods can be complementarily used in the postoperative follow up. Depending on the operated structure the choice of methods usually depends on local equipment availability and personal doctor's experience. MRI is probably best fitted for evaluation of the internal knee structures such as cruciate ligaments and hyaline cartilage on the tibia and patella. US is my choice always in the evaluation of the superficially located connective tissue structures, femoral cartilage and menisci. In both cases the learning curve is nearly flat, frustrating and dedicated to only those radiologist who know how their surgeon looks like with and without a surgical mask. Tight surgeon radiologist cooperation and information exchange is essential in this kind of diagnostics. PMID- 17344011 TI - Relationship between the arterial calcification detected in mammography and coronary artery disease. AB - OBJECTIVE: Arterial calcification is frequently encountered in mammography. The frequency of breast arterial calcification (BAC) increases with increasing age. Studies have shown that BAC is seen more frequently among the people who are under the risk of coronary artery diseases (CAD) such as diabetes and hypertension. The objective of this study is to investigate the relationship between the arterial calcification detected in mammography and the CAD. MATERIAL AND METHODS: Screening mammography was performed in 123 women above the age of 40 years who had been examined with coronary angiography for the evaluation of CAD. The presence of BAC, number of affected vessels, and the distribution of calcification in the vessel wall were evaluated in the mammography. Subjects were questioned in terms of the cardiovasculary risk factors. The severity of CAD was evaluated according to the Gensini scoring. In addition, the number of blood vessels with stenosis of more than 50% was used as the vascular score. The correlation between Gensini and the vascular scores, and BAC was statistically evaluated using Mann-Whitney U and Kruskal-Wallis tests. RESULTS: Eighty (65%) of 123 patients had CAD. BAC was detected in the mammography of 49 (39.8%) subjects. The ages and duration of menopause of the cases with BAC were significantly higher than those without BAC (p<0.001). There was an almost significant correlation between the BAC and Gensini scores (p=0.059). There was a significant increase in the frequency of BAC among subjects with more than two vessels with stenosis (p=0.033). CONCLUSION: Frequency of BAC increases with increasing age. BAC is also frequently seen in subjects having severe coronary artery disease. Although increasing age may be a factor increasing the frequency of BAC, BAC may also be an indicator of CAD. Therefore, the mentioning of arterial calcification in mammography reports may be important in warning the clinician in terms of CAD. PMID- 17344012 TI - Crohn's disease at the small bowel imaging by the ultrasound-enteroclysis. AB - Crohn's disease is more likely a systemic disease governed by a shift in the immune response, thus affecting the whole MALT system. Its treatment should be as conservative as possible and surgery is usually taking place after complications like indolent fistulations, stenoses, bleeding, or bowel perforation started. Standard radiological methods to check the extent of the disease are loaded either with certain radiation exposure (enteroclysis, CT) or lack standardization (ultrasound). The aim of this small study was to evaluate the worth of ultrasound enteroclysis in detecting the extent and complications of the Crohn's disease in surgically treated patients. MATERIAL AND METHODS: Since 1997, when we started with the ultrasound-enteroclysis, 246 surgical performances were involved into our study. Out of them, 181 had conventional abdominal intestinal ultrasound as well as conventional enteroclysis within 1 week. Remaining 65 cases were diagnosed by the ultrasound-enteroclysis. Intestinal ultrasound was performed on the Ultramark 3000 HDI device with autofocussable convex 5 MHz and linear 7.5 MHz probes or nowadays ATL 5000 HDI, 7-12 MHz linear probe. No contrast enhancement was used. Enteroclysis was done with the Micropaque suspension diluted 1:1 with HP-7000 300 ml with its application rate up to 75 ml/min followed by HP-7000 solution 2000 ml, application rate of 120 ml/min. The patients with ultrasound enteroclysis were applied HP 7000 solution only (2000 ml, rate 100ml/s) via an enteroclysis catheter. All investigations were video-recorded. RESULTS: Consent with the per-operative finding was reached in 162 from 181 enteroclyses and in 169 of 181 ultrasounds. Ultrasound-enteroclysis was precise in 61 cases from 65. Among these, 60 patients had the recurrence during the treatment proved by clinical and laboratory results. This re-activation was clearly revealed in 38 from 43 cases by enteroclysis, 41 from 43 by US and in 16 from 17 by ultrasound enteroclysis. From 30 patients that developed acute complication non-responding to the conservative therapy (abscesses, fistulas and intestinal obstructions) there were 18 from 20 accurately diagnosed by enteroclysis, only 12 from 20 by US and 9 from 10 by US-enteroclysis. The differences were either statistically non significant or there were too small numbers to give sensible statistical results, but low sensitivity of ultrasound in complications (p=0.05). CONCLUSION: US enteroclysis seems to became the standard examination of patients with Crohn's disease mainly in those with unclear conventional ultrasound. The most important fact is that this examination significantly decreases the radiation load when maintaining high sensitivity. This is very important namely in patients with Crohn's disease that require life-long observation and repeated examinations. This examination is much more easy to standardize than the conventional US. PMID- 17344013 TI - Cleaning validation 2: development and validation of an ion chromatographic method for the detection of traces of CIP-100 detergent. AB - A cleaning validation method, ion chromatographic method with conductivity detection was developed and validated for the determination of traces of a clean in-place (CIP) detergent. It was shown to be linear with a squared correlation coefficient (r(2)) of 0.9999 and average recoveries of 71.4% (area response factor) from stainless steel surfaces and 101% from cotton. The repeatability was found to be 2.17% and an intermediate precision of 1.88% across the range. The method was also shown to be sensitive with a detection limit (DL) of 0.13 ppm and a quantitation limit (QL) of 0.39 ppm for EDTA, which translates to less than 1 microL of CIP diluted in 100mL of diluent in both cases. The EDTA signal was well resolved from typical ions encountered in water samples or any other interference presented from swabs and surfaces. The method could be applied to cleaning validation samples. The validated method could be included as a suitable one for rapid and reliable cleaning validation program. PMID- 17344014 TI - High-performance liquid chromatographic method for the determination and pharmacokinetic study of oxypeucedanin hydrate and byak-angelicin after oral administration of Angelica dahurica extracts in mongrel dog plasma. AB - A high-performance liquid chromatographic method was developed and validated for the determination and pharmacokinetic study of oxypeucedanin hydrate and byak angelicin after oral administration of Angelica dahurica extracts in mongrel dog plasma. The coumarin components and the internal standard isopsoralen were extracted from plasma samples with the mixture of tert-butyl methyl ether and n hexane (4:1, v/v). Chromatographic separation was performed on a C(18) column (200 mm x 4.6mm, 5 microm) with the mobile phase acetonitrile-methanol-water acetic acid (20:15:65:2, v/v/v/v) at a flow-rate of 1.0 ml/min. Only the peak of oxypeucedanin hydrate and byak-angelicin could be detected in dog plasma after oral administration of ethanol extracts of A. dahurica mainly containing xanthotoxol, osthenol, imperatorin, oxypeucedanin hydrate and byak-angelicin. The calibration curves of oxypeucedanin hydrate and byak-angelicin were linear over a range of 22.08-8830.00 and 6.08-2430.00 ng/ml in dog plasma, respectively. The quantification limit of oxypeucedanin hydrate and byak-angelicin in dog plasma was 22.08 and 6.08 ng/ml, respectively. The intra- and inter-day precision was less than 7.6% and 8.5% and the accuracy was from 91.9% to 106.1%. The lowest absolute recoveries of oxypeucedanin hydrate and byak-angelicin were 85.7% and 87.0%, respectively. The method was successfully applied to the pharmacokinetic studies of oxypeucedanin hydrate and byak-angelicin in dog plasma after oral administration of ethanol extracts from A. dahurica. PMID- 17344015 TI - Development of an illustrated medication schedule as a low-literacy patient education tool. AB - OBJECTIVE: Patients with low health literacy have difficulty understanding prescription drug labels and other medication instructions. This article describes the development, implementation, and preliminary evaluation of an illustrated medication schedule (a "pill card") that depicts a patient's daily medication regimen using pill images and icons. METHODS: Participants in a randomized controlled trial who were assigned to receive the pill card intervention described their use of the card and its perceived effectiveness. Responses were analyzed by level of patient literacy and other characteristics. RESULTS: Among the 209 respondents, 173 (83%) reported using the pill card when they initially received it, though use declined to 60% approximately 3 months later. Patients with inadequate or marginal literacy skills, less than high school education, or cognitive impairment were most likely to refer to the card on a regular basis initially and at 3 months (p<0.05). Most pill card users (92%) rated the tool as very easy to understand, and 94% found it helpful for remembering important medication information, such as the name, purpose, or time of administration. CONCLUSION: Nearly all patients considered an illustrated medication schedule to be a useful and easily understood tool to assist with medication management. Patients with limited literacy skills, educational attainment, or cognitive function referred to the aid with greater frequency. PRACTICE IMPLICATIONS: Picture-based instructions promote better understanding of prescription medications, particularly among patients with limited literacy skills or cognitive impairment, and should be used more widely in practice. PMID- 17344016 TI - Comment on "Blue-dye technique complements four-node sampling for early breast cancer". PMID- 17344017 TI - The role of staging laparoscopy in oesophagogastric cancers. AB - AIMS: Selection of patients for treatment of oesophagogastric cancers rests on accurate staging. Laparoscopy has become a safe and effective staging tool in upper gastrointestinal cancers because of its ability to detect small peritoneal and liver metastases missed by imaging techniques. The aim of this study was to evaluate the role of staging laparoscopy (SL) in determining resectability of oesophagogastric cancers. METHODS: A review of 511 patients with oesophagogastric cancers referred to our centre during a 7-year period was performed. Four hundred and sixteen of them assessed to have resectable tumours after preoperative staging with CT and/or ultrasound underwent SL. The main outcome measure was the number of patients in whom laparoscopy changed treatment decision. RESULTS: Staging laparoscopy changed treatment decision in 84 cases (20.2%): locally advanced disease in 17, extensive lymph node disease in four and distant metastases (liver and peritoneum) in 63 cases. The sensitivity of laparoscopy for resectability was 88%. Eighty-one percent of patients who had combined CT scan and EUS were resectable at surgery compared with 65% of those who had CT scan alone (statistically significant with P-value<0.05). Of those patients deemed resectable by SL 8.1% were found to be unresectable at laparotomy, 16 with locally advanced disease and 11 with metastases. CONCLUSION: Staging laparoscopy avoided unnecessary laparotomy in 20.2% of our patients and was most useful in adenocarcinoma, distal oesophageal, GOJ and gastric cancers and probably not necessary in lesions of the upper two-third of the oesophagus. PMID- 17344018 TI - Use of preoperative lymphoscintigraphy and intraoperative gamma-probe detection for identification of the sentinel lymph node in patients with papillary thyroid carcinoma. AB - AIMS: Lymph node metastases for papillary thyroid carcinoma are associated with an increased incidence of locoregional recurrence. The use of preoperative lymphoscintigraphy and intraoperative gamma probe detection to localize the sentinel lymph node in papillary thyroid carcinoma was investigated. METHODS: From February 2004 to December 2005 the sentinel lymph node technique was studied in 64 consecutive patients with cytological evidence of papillary thyroid carcinoma. The day before surgery, patients were submitted to US-guided peri tumoural injection of the radiotracer and a lymphoscintigraphy was performed. In the operating room a total thyroidectomy was done, and thanks to a hand-held gamma probe the sentinel lymph node and all lymph nodes, belonging to the sentinel node compartment, were removed. RESULTS: The gamma probe identified the sentinel lymph node in 62 patients (96.8%). We found 48 (77.5%) sentinel lymph node without metastases; 12 (19.3%) with metastases and 2 (3.2%) with micrometastases. In 7 cases (11.3%), with a negative sentinel lymph node, metastases in other nodes of the same region were recorded. In 22 cases (34.3%) the ultrasound give an erroneous indication (P=0.004). Five patients (8.0%), 4 with multifocal cancer, had a positive postoperative lymphoscintigraphy. CONCLUSION: This study shows that the sentinel lymph node technique for papillary thyroid carcinoma is feasible, repeatable, and more accurate than preoperative ultrasound. In cases of multifocal thyroid lesions more patients should be enrolled to establish the utility of the radio-guided technique. PMID- 17344019 TI - [Anaesthetic management with spontaneous breathing for cardiac tamponade]. PMID- 17344020 TI - AIDS: the genomic hole. PMID- 17344021 TI - Effects of bromodichloromethane on ex vivo and in vitro luteal function and bromodichloromethane tissue dosimetry in the pregnant F344 rat. AB - Bromodichloromethane (BDCM), a drinking water disinfection by-product, causes pregnancy loss, i.e. full-litter resorption, in F344 rats when treated during the luteinizing hormone (LH)-dependent period. This effect is associated with reduced maternal serum progesterone (P) and LH levels, suggesting that BDCM disrupts secretion of LH. To test the hypothesis that BDCM also affects luteal responsiveness to LH, we used ex vivo and in vitro approaches. For the ex vivo study (i.e., in vivo exposure followed by in vitro assessment), dams were dosed by gavage on gestation days (GD) 6-9 (plug day=GD 0) at 0 or 100 mg/kg/d. One hour after the GD-9 dose, rats were killed, blood was collected, and tissue concentrations of BDCM were assessed. Corpora lutea (CL) were incubated with or without hCG, an LH agonist, to stimulate P secretion. For the in vitro study, CL were pooled from untreated F344 rats on GD 9 and cultured with BDCM at 0, 0.01, 0.10 or 3.0 mM. BDCM was found at highest concentrations in adrenal, ovarian, adipose, and hypothalamic tissues. BDCM treatment decreased serum P and LH levels in vivo. Ex vivo, however, BDCM-exposed CL showed >2-fold increases in P secretion relative to controls. Both control and BDCM-exposed CL displayed a 2.4 fold increase in P secretion in response to hCG challenge. In contrast, in vitro exposures reduced CL responsiveness in a dose-related fashion while baseline levels were unaffected. It is unclear if the ex vivo 'rebound' reflects the removal of the CL from a possible direct inhibitory influence of BDCM, or a response to diminished LH stimulation in vivo. Thus, these data suggest that BDCM disrupts pregnancy in F344 rats via two modes: disruption of LH secretion, and disruption of the CL's ability to respond to LH. PMID- 17344022 TI - Restraint stress impairs early wound healing in mice via alpha-adrenergic but not beta-adrenergic receptors. AB - Stress negatively influences wound healing in a clinically relevant manner. In an animal model, repeated restraint stress (RST) impairs wound healing in mice, partially through stress-induced glucocorticoid (GC) release. However, the role of stress-induced catecholamines (i.e., (nor)epinephrine) in healing has not been elucidated. In the present study, two 3.5mm round dermal wounds were placed on the backs of mice. Animals were restrained overnight for 3 days prior to and 5 days post-wounding. Prior to RST, mice were injected with either phentolamine or nadolol: non-specific alpha- and beta-adrenergic receptor antagonists, respectively. Pictures were taken daily to measure the rates of wound closure and contraction. Blockade of alpha-adrenergic, but not beta-adrenergic receptors, attenuated impairments in wound closure and contraction, and normalized edema, in RST mice. Thus, although stress impairment in wound healing clearly involves GCs, catecholamines play an important role via alpha-adrenergic receptor stimulation. PMID- 17344023 TI - Unilateral, clinically T2N0, squamous cell carcinoma of the tongue: surgical outcome analysis. AB - To determine the survival rate and analyse the predicting factors of recurrence in patients with unilateral, clinically T2N0 squamous cell carcinoma (SCC) of the tongue which does not cross the midline, a retrospective analysis of 32 such consecutive, previously untreated, cases was performed. All patients were initially treated by surgery between January 1992 and May 2004. All patients had neck dissections: 12 continuous, 20 discontinuous, 24 bilateral and 8 unilateral. Fourteen patients (44%) received adjunctive postoperative radiotherapy. Occult metastatic rates were 34% and 4% in ipsilateral and contralateral neck, respectively. Patients with pN0 cancer had a better 5-year disease-specific survival rate than those with pN+ cancer (85% versus 41%, P=0.005). Twelve patients (38%) had recurrences after the initial treatment. The recurrence rate was significantly higher in patients with pathologic nodal metastasis, peroral resection of the primary tumour or discontinuous neck dissection. The results suggest that the most effective surgical methods for treating unilateral T2N0 SCC of the tongue which does not cross the midline are: pull-through approach for primary lesion instead of peroral approach; continuous rather than discontinuous neck dissection and ipsilateral elective rather than bilateral routine elective neck dissection. PMID- 17344024 TI - Increased NKCC1 expression in refractory human epilepsy. AB - Cation-chloride co-transporters (CCTs), particularly NKCC1, may be important in epileptogenesis. We have performed a detailed histological examination of NKCC1 in large samples of patients with hippocampal sclerosis (HS) or focal cortical dysplasia (FCD), pathologies both commonly associated with pharmacoresistant epilepsy. We consistently found increased immunoreactivity for NKCC1 in HS and FCD, but not in adjacent histologically normal cortex. Our results suggest that NKCC1 might contribute to the pathogenesis or pathophysiology of HS and FCD, thereby potentially offering a new therapeutic target in the treatment of pharmacoresistant epilepsy. PMID- 17344025 TI - Cognitive function in childhood and early adulthood and hospital admission for schizophrenia and bipolar disorders in Danish men born in 1953. AB - OBJECTIVE: This study examines the influence of cognitive function and change in cognitive function during adolescence on schizophrenia and bipolar disorders in adulthood and explores possible mechanisms for any associations. METHOD: A cohort of 6923 men born in Copenhagen, Denmark in 1953, who had completed assessments of cognitive performance (measured by a total test score that combines verbal, arithmetic and spatial functions) at ages 12 and 18, were followed from 1972 until 2002. Psychiatric outcomes (hospital admissions for schizophrenia and bipolar disorders) were obtained from the Danish Psychiatric Register. RESULTS: During the follow-up period 133 of the men had a discharge diagnosis of schizophrenia or schizophrenia spectrum disorder. Cognitive function measured at both ages 12 and 18 years was inversely associated with these disorders (unadjusted hazard ratio (HR) per SD of cognitive function at age 12: 0.87 (95% CI: 0.75,1.05) and at age 18: 0.72 (95% CI: 0.60,0.86)). Adjustment for birth weight, social circumstances during childhood, indicators of social integration and educational attainment at age 18 years changed these associations only slightly. When cognitive function measured at ages 12 and 18 were entered in the same model only the latter was inversely associated with risk of schizophrenia or spectrum disorder. Decline in cognitive function between ages 12 and 18 was associated with an increased risk of schizophrenia spectrum disorder (HR: 1.32 (95% CI: 1.01,1.75)). Cognitive function at both ages also showed an inverse association with bipolar disorders, though the association was imprecisely estimated due to small numbers (N=16). CONCLUSIONS: Low cognitive function at ages 12 and 18 years and cognitive decline between these two ages were associated with increased risk of schizophrenic disorders. This suggests that reduction in cognitive function during childhood may be an early symptom of these outcomes. PMID- 17344026 TI - Effects of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on executive function in schizophrenia. AB - BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been associated with both overall schizophrenia risk and severity of negative symptoms. This study examined whether schizophrenia patients homozygous for the risk allele (T/T) exhibit greater impairment in executive function, and determined the extent to which MTHFR's effects on negative symptoms underlie this relationship. METHODS: 200 outpatients with chronic schizophrenia were evaluated with the Verbal Fluency Test (VFT), Wisconsin Card Sort Test (WCST), and California Verbal Learning Test (CVLT). Performance was stratified by MTHFR C667T genotype. Path analysis determined the extent to which MTHFR effects on negative symptoms mediated the relationship between genotype and cognitive measures. RESULTS: T/T subjects exhibited significantly greater deficits on the VFT and had more difficulty achieving the first category on the WCST. Genotype groups did not differ in CVLT performance. C677T effects on negative symptoms contributed to, but did not fully account for, genotype effects on VFT. Negative symptoms did not mediate WCST performance. CONCLUSIONS: MTHFR C677T genotype contributes to certain executive function deficits in schizophrenia. These deficits remained significant when taking into account mediating effects of negative symptoms. Although the intermediate mechanisms for C677T effects remain uncertain, these results suggest that MTHFR-related cognitive impairment and negative symptoms reflect differing neural substrates. PMID- 17344027 TI - Impaired executive performance in healthy siblings of schizophrenia patients in a population-based study. AB - There is increasing evidence that healthy siblings of schizophrenia patients have similar, although milder, neuropsychological deficits than their affected family members. However, the interpretation of these findings has been complicated by methodological differences, for example the selection of relatives studied and the sensitivity of tests used. We studied neuropsychological functioning in schizophrenia families in representative, population-based samples of schizophrenia patients (n=81) and healthy siblings (n=78) from 58 families, and control subjects (n=70). We found that the healthy sibling group was impaired in tests measuring performance speed and executive functions. The patients were significantly impaired in all neuropsychological variables studied when compared with the control subjects, and also when compared with the healthy siblings. The effects of age, sex and education were controlled for. In conclusion, in a study of representative, population-based sample the healthy siblings of schizophrenia patients demonstrated deficits in processing speed and executive functions. PMID- 17344028 TI - Neurocognitive indicators for a conversion to psychosis: comparison of patients in a potentially initial prodromal state who did or did not convert to a psychosis. AB - The study aims to identify potential neurocognitive indicators of an enhanced risk for developing psychosis. N=44 patients meeting clinical inclusion criteria for initial prodromal states (IPS) who developed psychosis within a median interval of 10 months were compared to N=39 IPS patients not developing psychosis within a minimum interval of 1 year (median 36 months), and to N=44 healthy controls on a comprehensive neuropsychological test battery (pattern recognition, divided and sustained attention, spatial and verbal working memory, verbal/visual memory, speed of processing, executive and intellectual functions). IPS patients who converted to psychosis performed worse than healthy controls on all broad neurocognitive domains. They were more impaired than IPS patients not developing psychosis on the Subject Ordered Pointing Task (SOPT; working memory), verbal memory functions, verbal executive, verbal IQ and speed of processing tests. After a Bonferroni-Holms adjustment for multiple testing differences on SOPT, Digit-Symbol Test, and verbal IQ remained significant (effect sizes d=0.54-0.88). Neurocognitive predictors had a sensitivity of 0.75 and a specificity of 0.79. Results support several cognitive domains as indicators of vulnerability to psychosis, and additionally suggest that subtle deficits in verbal abilities (working and long-term memory, executive and intellectual functions) and decreased speed of processing may help to predict conversion to psychosis in a clinically defined IPS group. PMID- 17344029 TI - Antimicrobial susceptibility of Bordetella pertussis isolates in the state of Washington. PMID- 17344030 TI - The Ham D(6) is more homogenous and as sensitive as the Ham D(17). AB - OBJECTIVE: Using the data of a positive d.b.c.t. comparing an hypericum extract (W55570) to placebo in depressed patients we explored whether the Ham D(6) was unidimentional and in case of a positive answer whether the total score was as sensitive as the total score of the Ham D(17). METHODS: The study was a 6 weeks double blind placebo controlled trial comparing 300 mg of hypericum t.i.d (n=186), to placebo (n=189), in patients with a single or recurrent depression according to DSM-IV. Superiority of hypericum versus placebo on the main outcome criterion (HDRS 17) was already published. The unidimensionality of the Hamilton depression scale 6 and 17 items were tested using a Mokken scale analysis. The effect size according to the initial severity of depression was calculated on the ITT last observation carried forward population. RESULTS: The Ham D(6), covering the core symptoms of depression was unidimensional, implying that improving this score reflects a true antidepressant effect. The Ham D(17) was not unidimensional. Hypericum was an effective antidepressant in patients with a pre treatment score of 12 or more (n=208) on the Ham D(6), the effect size was 0.46. No difference with placebo was observed for those with a score of less than 12 (n=167). CONCLUSIONS: For the evaluation of an antidepressant effect, because of its specificity and sensitivity, the Ham D(6) should be used as a primary outcome measure rather than the Ham D(17). PMID- 17344031 TI - Sexual differences in the completed suicides in Turkey. AB - The aim of this study was to determine whether there is a difference between men and women in terms of suicide age, suicide method and suicide reason in Turkey. This study recruited 17,327 cases that had committed suicide between 1990 and 2000. Of all the cases who committed suicide during a period of 11 years, 61.1% were men, 38.9% women. The highest suicide score fell into the age group 15-24 (P<0.001). The most frequently used methods for suicide were self-hanging (48.2%) and use of firearms (19.2%) (P<0.001). The proportion of those committing suicide taking chemicals (drugs, etc.) was higher in women than in men (P<0.001). The most frequently seen reasons for suicide were illness and (33.8%) unsatisfactory relationships (33.0%) (P<0.001, each one). Women committed suicide much more because of unsatisfactory relationships, whereas for men it was due to illness (20.8% and 14.6%, respectively). There were significant differences between men and women in terms of suicide age, suicide method and suicide reason in Turkey. When evaluating suicide cases it is essential that the differences between sexes be taken into consideration. PMID- 17344032 TI - Sexual dysfunction in patients with schizophrenia on antipsychotic medication. AB - OBJECTIVE: The objective of this study was to determine the prevalence of sexual dysfunction in patients with schizophrenia under antipsychotic therapy and to investigate the effect of various parameters on sexual dysfunction. METHOD: A total of 827 stabilized outpatients who met DSM-IV criteria for schizophrenia, were recruited in the study. Arizona Sexual Experience Scale (ASEX) and the subscale on sexual function of the UKU Side Effects Rating Scale were applied at a single interview. RESULTS: In total, 52.6% of the patients had sexual dysfunction, 54.2% reported a low sexual desire and 41.7% reported problems in having an orgasm. Erectile dysfunction and ejaculation problems were seen in 48.1% and 64.2% of the men, respectively; amenorrhea was seen in 24.9% of the women. ASEX score and severity of disease were found to be correlated (p=0.02). Higher ASEX scores were observed in patients who smoked (p=0.01). Men receiving atypical monotherapy had lower ASEX scores than those receiving a combination of atypical and conventional antipsychotics (p=0.017). Patients on combination therapy had more ejaculation problems than the atypical group (p=0.001). Low sexual desire was more prevalent among women using conventional drugs than those on atypical drugs (p=0.004). In linear regression analyses, ASEX was affected significantly and independently by the severity of the disease only in men (p=0.005). CONCLUSION: Our results show that sexual dysfunction is widespread among patients with schizophrenia on antipsychotic medications. PMID- 17344033 TI - Reduced platelet vesicular monoamine transporter density in Tourette's syndrome pediatric male patients. AB - The vesicular monoamine transporter (VMAT2) plays a major role in the synaptic accumulation and quantal release of monoamines. In this study, we assessed high affinity [(3)H]dihydrotetrabenazine binding to platelet VMAT2, in a group of untreated male Tourette's syndrome (TS) patients (age: 8-17.5 years, n=9) and in a group of age- and sex-matched healthy controls (age: 9-16 years, n=16). Significantly decreased platelet VMAT2 density (B(max)) (-23%, p=0.016) was observed in the TS patients. The affinity (K(d)) of the ligand to platelet VMAT2 was similar in both groups. If the lower platelet VMAT2 density also occurred in the brain, it may have serve as an adaptive mechanism geared to decrease dopamine storage in the presynaptic neurons and thereby to attenuate the dopaminergic overactivity and ameliorate the movement disorder. PMID- 17344034 TI - Additional support for linkage of schizophrenia and bipolar disorder to chromosome 3q29. AB - After publishing a genome scan and follow-up fine mapping, suggesting schizophrenia and bipolar disorder linkage to chromosome 3q29, we now genotyped 11 additional SNPs (single nucleotide polymorphisms), in order to narrow down a potential candidate region. Linkage was performed using the GENEHUNTER program version 2.1r3. A NPL score Z(all) of 3.891 (p=0.000156) was observed with SNP rs225. In short, we found significant linkage scores most telomeric on chromosome 3q29, spanning 3.46 Mbp (7 SNPs). PMID- 17344035 TI - Segregation of postembryonic neuronal and glial lineages inferred from a mosaic analysis of the Drosophila larval brain. AB - Due to its intermediate complexity and its sophisticated genetic tools, the larval brain of Drosophila is a useful experimental system to study the mechanisms that control the generation of cell diversity in the CNS. In order to gain insight into the neuronal and glial lineage specificity of neural progenitor cells during postembryonic brain development, we have carried an extensive mosaic analysis throughout larval brain development. In contrast to embryonic CNS development, we have found that most postembryonic neurons and glial cells of the optic lobe and central brain originate from segregated progenitors. Our analysis also provides relevant information about the origin and proliferation patterns of several postembryonic lineages such as the superficial glia and the medial anterior Medulla neuropile glia. Additionally, we have studied the spatio temporal relationship between gcm expression and gliogenesis. We found that gcm expression is restricted to the post-mitotic cells of a few neuronal and glial lineages and it is mostly absent from postembryonic progenitors. Thus, in contrast to its major gliogenic role in the embryo, the function of gcm during postembryonic brain development seems to have evolved to the specification and differentiation of certain neuronal and glial lineages. PMID- 17344036 TI - Physiological changes in barley plants under combined toxicity of aluminum, copper and cadmium. AB - Crop production on acid soil is markedly reduced, further, a multiple heavy metal pollution except Al on acid soil is detected in many areas. The present study was undertaken to assess the toxicities of Al, Cd, and Cu separately and in combinations, three heavy metals very often coexisting on acid soil, and to identify their interactions in two kinds of barley seedlings differing in Al tolerance. The plant growth, metals accumulations, total soluble protein and sugar contents, MDA contents and the activities of SOD and POD were estimated in roots and leaves after 5-week supply of the heavy metals excess in the nutrient solution. The results indicated that the stress treatments including low pH (pH 4.5) alone all adversely affected plant growth and disturbed the cell metabolism seriously. The development of toxic symptoms corresponded to a high accumulation of Al, Cd, Cu and to a poor increase in soluble sugar contents but to a high increase in MDA contents, to the decrease in soluble protein contents and to the much elevated SOD and POD activities in both roots and leaves. In addition, binary metal combinations of Al+Cd and Al+Cu both produced the synergistic response for the growth of barley seedlings, in particular for Shang 70-119, while, ternary metal combination of Al+Cu+Cd produced different interactions in two kinds of genotypes, thus, the significant synergistic response was seen in Shang 70-119, but the antagonistic response was detected in Gebeina. The different responses to ternary metal combination of two genotypes may result from the different metal bioaccumulation patterns, hence, the existence of Cd and Cu promoted Al accumulation in Shang 70-119 but inhibited Al accumulation in Gebeina. PMID- 17344037 TI - Photochemical control of network structure in gels and photo-induced changes in their viscoelastic properties. AB - Poly(amide acid) gels containing photosensitive azobenzene groups in the main chain have been synthesized and their viscoelastic properties before and after light irradiation have been investigated by dynamic viscoelasticity measurements. It was found that 405 nm light induced a local volume change and a two-fold increase in the storage modulus of the gels. We discuss the change in storage modulus upon light irradiation quite simply in terms of classical rubber elasticity theory, which cannot explain this large increase in storage modulus. The photo-induced increase in storage modulus may result from an increase in entanglement interactions of topological constraints fixed in the network structure, caused by photoisomerization of the azobenzene moieties. We suggest that topological constraints in the network structure of the gels were realized by light irradiation and calculate the resulting slip link ratio (index of the topological constraints) in the gel network. PMID- 17344038 TI - Exploring large-scale brain networks in functional MRI. AB - Increasing emphasis has been recently put on large-scale network processing of brain functions. To explore these networks, many approaches have been proposed in functional magnetic resonance imaging (fMRI). Their objective is to answer the following two questions: (1) what brain regions are involved in the functional process under investigation? and (2) how do these regions interact? We review some of the key concepts and corresponding methods to cope with both issues. PMID- 17344039 TI - [Ibuprofen in childhood: evidence-based review of efficacy and safety]. AB - Ibuprofen is the non-steroidal anti-inflammatory drug most prescribed for the treatment of fever and moderate pain in childhood. Its analgesic and antipyretic efficacy is now well documented: at equal doses ibuprofen appears slightly more effective than acetaminophen in the treatment of fever and is equivalent for analgesia. However, adverse effects should be taken into account in the choice between ibuprofen and acetaminophen. Lot of studies (case reports, cohort studies, case-control studies and one multicenter double-blind randomized control trial) have reported ibuprofen adverse effects at therapeutics doses. These data suggest there is an increased risk of invasive group A streptococcal infection after chickenpox and of acute renal failure in case of hypovolemia after a treatment by ibuprofen. Gastroduodenal and hemorrhagic adverse events could also happen, but the causality with ibuprofen is not demonstrated. Therefore, ibuprofen is not recommended for the treatment of fever or moderate pain during chickenpox or during a disease with a risk of dehydration, until other pharmacoepidemiology studies more accurately quantify the risk of adverse events of ibuprofen in children. PMID- 17344040 TI - [A large improvement in prescription of oral rehydration therapy in infants with acute diarrhoea]. PMID- 17344041 TI - The uPA receptor and the somatomedin B region of vitronectin direct the localization of uPA to focal adhesions in microvessel endothelial cells. AB - Vitronectin is a plasma protein which can deposit into the extracellular matrix where it supports integrin and uPA dependent cell migration. In earlier studies, we have shown that the plasma protein, vitronectin, stimulates focal adhesion remodeling by recruiting urokinase-type plasminogen activator (uPA) to focal adhesion sites [Wilcox-Adelman, S. A., Wilkins-Port, C. E., McKeown-Longo, P. J., 2000. Localization of urokinase-type plasminogen activator to focal adhesions requires ligation of vitronectin integrin receptors. Cell. Adhes. Commun.7, 477 490]. In the present study, we used a variety of vitronectin constructs to demonstrate that the localization of uPA to adhesion sites requires the binding of both vitronectin integrin receptors and the uPA receptor (uPAR) to vitronectin. A recombinant fragment of vitronectin containing the connecting sequence (VN(CS)) was able to support integrin-dependent adhesion, spreading and focal adhesion assembly by human microvessel endothelial cells. Cells adherent to this fragment were not able to localize uPA to focal adhesions. A second recombinant fragment containing both the amino-terminal SMB domain and the CS domain was able to restore the localization of uPA to adhesion sites. This fragment, which contains a uPAR binding site, also resulted in the localization of uPAR to adhesion sites. uPAR blocking antibodies as well as phospholipase C treatment of cells inhibited uPA localization to adhesion sites confirming a role for uPAR in this process. The SMB domain alone was unable to direct either uPAR or uPA to adhesion sites in the absence of the CS domain. Our results indicate that vitronectin-dependent localization of uPA to adhesion sites requires the sequential binding of vitronectin integrins and uPAR to vitronectin. PMID- 17344042 TI - Pressure sensing using a completely flexible organic transistor. AB - In this paper, we report on pressure sensors based on completely flexible organic thin film transistors (OTFTs). A flexible and transparent plastic foil (Mylar) is employed both as substrate and gate dielectric. Gold source and drain electrodes are patterned on the upper side of the foil while the gate electrode lies on the opposite side; a vacuum-sublimed pentacene film is used as active layer. The pressure dependence of the output current has been investigated by applying to the gate side of the device a mechanical stimulus by means of a pressurized airflow. Experimental results show a reversible dependence of the current on the pressure. The data analysis suggests that the current variations are due to pressure-induced variations of mobility, threshold voltage and possibly contact resistance. The drain current variation is reproducible, linear and reversible even though it displays a hysteresis. Moreover, the sensor responds very fast to the mechanical stimulus (i.e. within tens-hundreds of milliseconds) but the time required to reach the steady state is much higher (tens-hundreds of seconds). Electrical characteristics with and without applied pressure have been carried out in air without any extra ad hoc read-out circuit or equipment. The reported devices show potential advantages of flexibility of the structure, low cost and versatility of the device structure for sensor technologies. Many innovative and attractive applications as wearable electronics, e-textiles, e-skin for robots can be considered. PMID- 17344043 TI - Use of municipal solid waste compost (MSWC) as a growing medium in the nursery production of tomato plants. AB - Five media prepared from old peat (OP), white peat (WP) and municipal solid waste compost (MSWC) were used to determine optimum growing media for tomatoes (Lycopersicum esculentum Mill. cv "Atletico"). The mixtures of substrates used were: OP (65%)+WP (30%)+perlite (5%), OP (65%)+MSWC (30%)+perlite (5%), WP (65%)+OP (30%)+perlite (5%), WP (65%)+MSWC (30%)+perlite (5%), MSWC (65%)+WP (30%)+perlite (5%). Various seedling indices were measured in order to assess the quality of the nursery-produced plant. Nursery-produced tomato seedlings grown in WP (65%)+MSWC (30%) displayed quality indices similar to those recorded for conventional mixtures of old and white peat sphagnum, due to a correct balance between the compost nutrient supply and the porosity and aeration provided by white peat. PMID- 17344044 TI - Changes in gait while backward counting in demented older adults with frontal lobe dysfunction. AB - BACKGROUND: Gait disorders caused by dementia have been associated with frontal lobe dysfunction. Dual-tasking is used to explore the involvement of cortical level in gait control. It has been shown that dual-task induced gait changes that could be related to (1) the efficiency of executive function, (2) the level of difficulty involved in the walking-associated task, or (3) the articulo-motor components comprised in the walking-associated task. A better understanding of dual-task related changes in demented subjects with frontal lobe dysfunction could help us to clarify the role of the frontal lobe in motor gait control. OBJECTIVE: To assess and compare the effects of two mental arithmetic tasks involving similar articulo-motor components but different level of difficulty on the mean values and coefficient of variation (CV) of stride time among demented older adults with impaired executive function. METHODS: The mean values and coefficients of variation of stride time were measured using a GAITRite-System among 16 demented older adults with impaired executive function while walking with and without forward counting (FC) and backward counting (BC). RESULTS: The mean values and CV of stride time were significantly higher under both dual-task conditions than during a simple walking task (p<0.05). The change in CV of stride time during BC was significantly higher when compared with the change during FC (p=0.015), whereas the change in mean value was not significant (p=0.056). There was no difference between the dual-task and single task condition as far the number of enumerated figures were concerned (p=0.678 for FC and p=0.069 for BC), but significantly fewer figures were enumerated while BC compared with FC (p<0.001). CONCLUSION: BC provoked more changes in gait parameters than FC with major modification in gait variability related to an inappropriate focusing of attention. These findings suggest that the CV may be a suitable criterion for the assessment of gait control. PMID- 17344045 TI - Salvage of a failed odontoid screw. AB - Complications associated with anterior odontoid screw fixation, although not very common can be quite troublesome. We report a patient with early back-out of the implanted screw and its salvage with re-implantation of a longer screw. PMID- 17344046 TI - Effects of patellar resurfacing on contact area and contact stress in total knee arthroplasty. AB - The objective of this study was to examine the effects of patellar resurfacing on patellofemoral joint contact pressure and contact area in total knee arthroplasty. We tested seven fresh-frozen cadaveric knees using a custom knee jig which permits the simulation of physiologic quadriceps loading. Before patellar resurfacing, the mean peak contact pressure of medial and lateral patellofemoral joints was less than 10 MPa at knee flexion angles of 30 degrees, 60 degrees and 90 degrees, that of medial and lateral patellofemoral joints were 11.63 MPa and 11.42 MPa at a knee flexion angle of 120 degrees respectively, and the mean contact area of patellofemoral joint ranged from 70 to 150 mm2. After patellar resurfacing, the mean peak contact pressure of medial and lateral patellofemoral joints ranged from 50 to 100 Mpa (P<0.05), which exceeds the yield strength of ultrahigh molecular weight polyethylene, and the mean contact area of patellofemoral joint reduced to 10-15 mm2 (P<0.05). The contact pressure of patellofemoral joint was lower than the yield strength of articular cartilage before patellar resurfacing. Our results indicate that the yield stress of UHMWPE is exceeded after patellar resurfacing. PMID- 17344047 TI - Does arthroplasty type influence knee joint proprioception? A longitudinal prospective study comparing total and unicompartmental arthroplasty. AB - Proprioception was assessed after knee replacement to compare total (TKA) to unicompartmental (UKA) knee arthroplasty. Thirty-four patients were recruited; seventeen patients underwent TKA and seventeen patients underwent UKA. The patient's age was similar in both groups. Two measures of proprioception, joint position sense (JPS) and postural sway (PS) were measured. Function was assessed using the Oxford Knee Score (OKS). Measurements were taken pre-operatively and 6 months post-operatively on both the operated and contralateral leg. Pre operatively, no differences in JPS or PS were found between groups or between limbs in either group. Post-operatively, both groups had significant improvement of JPS in the operated limb only (20% increase). The improvement in JPS was similar in both groups. PS also improved significantly in both groups although the improvement of PS in the UKA group was twice that for the TKA group. The OKS improved by a similar amount in both groups. Both UKA and TKA result in a significant improvement in proprioception. Dynamic aspects of proprioception improve more after UKA than TKA, which may explain, in part, why UKA patients have superior functional outcome to that of TKA patients. PMID- 17344048 TI - A novel noninvasive method for assessing glutathione-conjugate efflux systems in the brain. AB - Brain efflux systems export such conjugated metabolites as glutathione (GSH) and glucuronate conjugates, generated by the detoxification process, from the brain and serve to protect the brain from harmful metabolites. The intracerebral injection of a radiolabeled conjugate is a useful technique to assess brain efflux systems; however, this technique is not applicable to humans. Hence, we devised a novel noninvasive approach for assessing GSH-conjugate efflux systems using positron emission tomography. Here, we investigated whether or not a designed proprobe can deliver its GSH conjugate into the brain. Radiolabeled 6 chloro-7-methylpurine (7m6CP) was designed as the proprobe, and [(14)C]7m6CP was prepared by the reaction of 6-chloropurine with [(14)C]CH(3)I as a model of [(11)C]CH(3)I. The radiochemical yield and purity of [(14)C]7m6CP were 10-20% and greater than 99%, respectively. High brain uptake (0.8% ID/g) at 1 min was observed, followed by gradual radioactivity clearance from the brain for 5-60 min after the injection of [(14)C]7m6CP into rats. Analysis of metabolites confirmed that the presence of [(14)C]7m6CP was hardly observed, and 80% of the radioactivity was identical to its GSH conjugate for 15-60 min. The brain radioactivity was single-exponentially decreased during the period of 15-60 min post-injection of [(14)C]7m6CP, and the first-order efflux rate constant of the conjugate, estimated from the slope, was 0.0253 min(-1). These results showed that (1) [(14)C]7m6CP readily entered the brain, (2) it efficiently and specifically transformed to the GSH conjugate within the brain, and (3) after [(14)C]7m6CP disappearance, the clearance of radioactivity represented the only efflux of GSH conjugate. We conclude that 7m6CP can deliver the GSH conjugate into the brain and would be useful for assessing GSH-conjugate efflux systems noninvasively. PMID- 17344050 TI - Electrochemical transfer of (18)F from (18)O water to aprotic polar solvent. AB - Electrochemical transfer of (18)F(-) from enriched [(18)O]-water to pure acetonitrile was investigated to develop a simple and effective synthesis of (18)F-radiopharmaceuticals. The transfer of (18)F is composed of two steps: first step is electro-deposition on a graphite anode and the next step is electro emission into pure acetonitrile by inversing the polarity of the electric tension. A sufficiently high fraction of the electro-emission, 73%, was achieved. The electrochemical transfer of (18)F to aprotic polar solvents without any additives, such as phase transfer catalysis, will make the synthesis of diverse (18)F-radiopharamceuticals simple and easy. PMID- 17344051 TI - Excitation functions of (alpha,xn) reactions on (nat)Rb and (nat)Sr from threshold up to 26 MeV: possibility of production of (87)Y, (88)Y and (89)Zr. AB - Excitation functions were measured by the stacked-foil technique for (nat)Rb(alpha,xn)(87m,87m+g,88)Y and (nat)Sr(alpha,xn)(86,88,89)Zr reactions from their respective thresholds up to 26 MeV. The samples for irradiation were prepared by sedimentation and pellet pressing techniques. The measured data were compared with those available in the literature. From the excitation functions, integral yields of the products were calculated. The suitable energy ranges for the production of (87)Y and (88)Y via (nat)Rb(alpha,xn) processes and of (89)Zr via the (nat)Sr(alpha,xn) process are E(alpha)=26-->20 MeV, E(alpha)=26-->5 MeV and E(alpha)=20-->8.5 MeV, respectively. The respective yields amount to 8.2, 0.08 and 0.9 MBq/microA h. Production of (88)Y is feasible if a waiting time of about 2 months is allowed to let the impurities decay out. Also, (87)Y can be produced with a relatively low impurity of (88)Y. The yields of both (88)Y and (87)Y via the present routes are, however, appreciably lower than those via the (nat)Sr(p,xn) processes. There is a possibility to produce (89)Zr via the alpha particle irradiation of (nat)Sr. The yield is rather low but would be considerably increased if enriched (86)Sr would be used as target material. The radionuclidic impurity levels in all the three products are discussed. PMID- 17344052 TI - Beta-amyloid causes downregulation of calcineurin in neurons through induction of oxidative stress. AB - Calcineurin is an abundant cytosolic protein that is implicated in the modulation of glutamate release. Here we show that the expression level of this enzyme is reduced in primary neuronal cultures treated with beta-amyloid. Parallel experiments in ETNA cell lines expressing SOD1 suggested that the effect of beta amyloid on calcineurin expression is mediated by oxidative stress. The relevance of the in vitro experiments was assessed by analysis of tissue from patients with Alzheimer's disease (AD) and tissue from two strains of transgenic mice that mimic aspects of AD. The tissue from the AD brains displayed a pronounced downregulation of calcineurin immunoreactivity in profiles that were negative for glial fibrillary acidic protein (GFAP). In the hippocampus of the transgenic animals (which were analyzed in an early stage of the disease) the downregulation of calcineurin was restricted to mossy fiber terminals. A downregulation of the presynaptic pool of calcineurin may contribute to the dysregulation of glutamate release that is considered a hallmark of AD. PMID- 17344053 TI - The elongation factor 1A: a novel regulator in the DNA replication/repair protein network in wheat cells? AB - Proliferating cell nuclear antigen (PCNA) is a DNA sliding clamp interacting with multiple partners in DNA transactions such as DNA replication/repair and recombination as well as chromatin assembly. We previously detected and purified by chromatographic procedures a 31 kDa PCNA from cultured wheat cells (Triticum monococcum L). Here we report the complete sequence of the wheat 31 kDa PCNA showing a very high aminoacid identity with its plant counterparts (maize and rice). This recombinant PCNA has been used as a bait in an affinity chromatography procedure, in order to capture PCNA interacting proteins. We detected by liquid chromatography, tandem mass spectrometry and search in plant protein databases, several specific bands from wheat cell lysates in fractions bound to wheat PCNA-affinity column. One of them is the wheat elongation factor 1A. Its putative regulatory role in DNA replication/repair is discussed. PMID- 17344054 TI - A novel gene, screened by cDNA-AFLP approach, contributes to lowering the acidity of fruit in apple. AB - cDNA-AFLP, coupled with bulked segregant analysis (BSA), was used to screen genes expressed differently between low- and high-acid apple fruits from hybrids of 'Toko' x 'Fuji' (Malus x domestica Borkh.). Sixty-four combinations of AFLP primers produced 2240 fragments, of which only one showed different expression between low- and high-acid fruits. The specific fragment was cloned and sequenced, and the complete cDNA was achieved by 3' and 5' rapid amplification of cDNA ends (RACE). The screened gene, designated as Mal-DDNA (GenBank accession no. DQ417661), showed no significant homology to clones in GenBank. The relatedness between fruit acidity and the transcription level of Mal-DDNA was identified by RT-PCR analysis on 30 hybrids. RT-PCR analysis indicated that Mal DDNA transcripted in low-acid fruits at both early and ripe stages whereas in high- and mid-acid fruits, it did not transcript at the early stage. RNA gel-blot hybridization indicated that Mal-DDNA transcripted only in fruits and had clear difference between low- and high/mid-acid fruits. There was a good indication that Mal-DDNA existed as one copy in apple genome by Southern blot. Possible regulation of Mal-DDNA in apple fruit acidity is also discussed in the paper. PMID- 17344055 TI - Regulation of the Arabidopsis thaliana vitamin B6 biosynthesis genes by abiotic stress. AB - Vitamin B(6) (pyridoxine and its vitamers) plays an essential role as a co-factor for enzymatic reactions and has also recently been implicated in defense against cellular oxidative stress. The biosynthetic pathway was thoroughly characterized in Escherichia coli, however most organisms, including plants, utilize an alternate pathway involving two genes, PDX1 and PDX2. Arabidopsis thaliana contains one copy of PDX2, but three full-length copies of PDX1, one each on chromosomes 2, 3, and 5 (referred to as PDX1.1, PDX1.2, and PDX1.3, respectively). Phylogenetic analysis of the PDX1 homologues in A. thaliana showed that PDX1.1 and PDX1.3 clustered with the homologues from the other dicots, whereas PDX1.2 was more divergent, and did not cluster with either the dicots or monocots. Expression analysis using quantitative PCR showed that PDX1.1 and PDX1.3 were highly expressed in A. thaliana rosettes, while PDX1.2 showed only low level expression. All three PDX1 genes and PDX2 were responsive to abiotic stressors including high light, chilling, drought, and ozone, however, the response of PDX1.2 was disparate from that of the other PDX genes, showing a lessened response to high light, chilling, and drought, but an increased response to ozone. Green fluorescent protein fusion studies demonstrated that PDX2 localizes in the nucleus and membranes of cells, consistent with recent published data for PDX1. Insight into regulation of the biosynthetic genes during abiotic stress could have important applications in the development of stress-tolerant crops. PMID- 17344056 TI - Evaluation of the 1-methyl-2-phenylindole colorimetric assay for aldehydic lipid peroxidation products in plants: malondialdehyde and 4-hydroxynonenal. AB - The 1-methyl-2-phenylindole colorimetric assay is considered specific for malondialdehyde (MDA) and 4-hydroxynonenal (HNE) in mammalian systems, but its specificity in plant tissues is unknown. This study demonstrates that the assay produces a purple/blue chromophore with an absorbance peak at 586 nm for a malondialdehyde standard, while aqueous extractions from Ribes spp. Beta vulgaris, and Lycopersicon esculentum tissues produce an orange chromophore with an absorbance maximum at 450 nm and a large shoulder that extends to 700 nm. No distinctive MDA peak was discernable in plant samples at lambda=586 nm and absorbance was attributed to background interference. The reaction between sucrose and 1-methyl-2-phenylindole produced an orange chromophore with a spectrum similar to those obtained from plant extractions, suggesting that simple sugars are the likely source of background interference. This study demonstrates that the 1-methyl-2-phenylindole colorimetric assay is non-specific for detecting MDA and HNE in plants and its use is cautioned due to interference, particularly from sugars. PMID- 17344057 TI - Alterations in secondary metabolism of aposymbiotically grown mycobionts of Xanthoria elegans and cultured resynthesis stages. AB - HPLC analyses of Xanthoria elegans cultivated on different media and either aposymbiontically or with its photobiont revealed that the carbon source and the presence of the algal partner have an impact on the secondary metabolism of the mycobiont. The aposymbiotically (without photobiont) grown mycobiont contained up to 70% more of the main compounds in its thallus than in resynthesis stage. Although this is speculative, the induction of the polyketide pathway may be a feedback mechanism to the absence of the photobiont. All cultures produce a variety of substances which were not detectable in the voucher specimen. Besides physcion (the major substance), we were able to identify emodin as well as physcion-bisanthrone, teloschistin monoacetate and derivatives. A strong inducible effect on the production of physcion, physcion-bisanthrone and on their precursors and derivatives was found for mannitol. By contrast, supplementation of ribitol had negligible effects, if any, on polyketide quantities although it is the main carbon source for the mycobiont in free-living lichens with Trebouxia photobiont. PMID- 17344058 TI - Characterisation of recombinant Hevea brasiliensis allene oxide synthase: effects of cycloxygenase inhibitors, lipoxygenase inhibitors and salicylates on enzyme activity. AB - Mechanical wounding and jasmonic acid (JA) treatment have been shown to be important factors in controlling laticifer differentiation in Hevea brasiliensis (rubber tree). With the long-term aim of potentially modifying the endogenous levels of JA in H. brasiliensis by gene transfer, we describe in this paper the molecular cloning of a H. brasiliensis allene oxide synthase (AOS) cDNA and biochemical characterisation of the recombinant AOS (His(6)-HbAOS) enzyme. The AOS cDNA encodes a protein with the expected motifs present in CYP74A sub-group of the cytochrome P450 super-family of enzymes that metabolise 13 hydroperoxylinolenic acid (13-HPOT), the intermediate involved in JA synthesis. The recombinant H. brasiliensis AOS enzyme was estimated to have a high binding affinity for 13-HPOT with a K(m) value of 4.02+/-0.64 microM. Consistent with previous studies, mammalian cycloxygenase (COX) and lipoxygenase (LOX) inhibitors were shown to significantly reduce His(6)-HbAOS enzyme activity. Although JA had no effect on His(6)-HbAOS, salicylic acid (SA) was shown to significantly inhibit the recombinant AOS enzyme activity in a dose dependent manner. Moreover, it was demonstrated that SA, and various analogues of SA, acted as competitive inhibitors of His(6)-HbAOS when 13-HPOT was used as substrate. We speculate that this effect of salicylates on AOS activity may be important in cross-talking between the SA and JA signalling pathways in plants during biotic/abiotic stress. PMID- 17344059 TI - Combined effects of selenium and drought on photosynthesis and mitochondrial respiration in potato. AB - The possible effects of selenium (Se) foliar spraying and drought were studied for 3 months in potato (Solanum tuberosum L.) cultivar Desiree in Ljubljana, Slovenia. Four combinations of treatments were conducted: well-watered plants with and without Se foliar spraying, and drought exposed plants with and without Se foliar spraying. The following parameters were monitored 2 and 4 weeks after treatments: net photosynthesis, transpiration rate, quantum yield of photosystem II (PSII), and respiratory potential measured by electron transport system activity. After 3 months of treatments, leaf water potential and tuber yield were determined. The content of Se in tubers was measured after harvesting time. Several effects of drought and Se foliar spraying and their combinations were found. Net photosynthesis and respiratory potential were lower in drought exposed plants 4 weeks after treatments. Se induced higher respiratory potential in the leaves 4 weeks after treatments. Higher efficiency of energy conversion in PSII, expressed by a higher effective quantum yield, was observed in Se treated plants 2 weeks after treatments. Foliarly applied Se was efficiently absorbed by plant leaves and transported to the tubers. PMID- 17344060 TI - Late coronary artery lesions after neonatal arterial switch operation: results of surgical coronary revascularization. AB - OBJECTIVE: To evaluate the results of surgical revascularization in children with coronary artery lesions following neonatal arterial switch operation (ASO). METHODS: Among 755 neonates who underwent ASO, there were 713 late survivors (94%). Coronary lesions were detected in 34 patients (5%). Coronary revascularization was carried out in 19 children (mean age: 5.6+/-3.2 years) in whom myocardial ischemia was demonstrated by myocardial perfusion imaging studies. Coronary lesions involved the left main coronary artery in 14 cases, the left anterior descending artery in 3, and the right coronary artery in 2. Sixteen patients had coronary angioplasty (left main coronary artery in 11, left anterior descending artery in 3, right coronary artery in 2). Two patients underwent a mammary bypass and one had a saphenous vein proximal bypass. RESULTS: There was no mortality or coronary event. Mean follow-up was 6.3+/-2.8 years. Patency of coronary repair was demonstrated in all patients; however, in one child with angioplasty of the left main coronary artery, there was a residual stenosis of the left anterior descending artery, and reoperation with a mammary bypass was required. Myocardial perfusion imaging was performed in 18 patients; myocardial perfusion was normal in 16 and 2 had minimal residual perfusion defects. Treadmill exercise testing was performed in 11 patients and was normal in all. CONCLUSIONS: (1) Following ASO, coronary lesions are not uncommon and they are progressive. Routine and sequential coronary evaluation is necessary. (2) Coronary revascularization can be achieved using coronary angioplasty in most cases. Mammary bypass may be used in selected circumstances. Normal myocardial perfusion is restored in most patients. PMID- 17344061 TI - Clinical characteristics and feasibility of thoracoscopic approach for congenital cystic adenomatoid malformation in adults. AB - OBJECTIVE: Congenital cystic adenomatoid malformation (CCAM) in adults is very rare, and surgical resection is the treatment of choice. We evaluated the clinical characteristics and feasibility and safety of video-assisted thoracic surgery (VATS) in adult patients with CCAM. METHODS: Retrospective analysis of nine consecutive adult patients with CCAM treated surgically between January 1995 and April 2006 at a single center. The clinical characteristics and surgical outcome were evaluated retrospectively. RESULTS: The records of five men and four women were examined. The median age at diagnosis was 30.5 years (range 16-44 years). The most frequent symptoms were cough (n=4) and hemoptysis (n=2). Three patients had recurrent respiratory infections. Chest computed tomography (CT) was reviewed in all cases. The lesions were on the right side in six patients and on the left in three. All patients had lesions in a single lobe, except one patient who had multi-lobar lesions. The CCAM appeared as thin-walled multi-septated cystic lesions in six patients and as parenchymal consolidations in three patients. Four patients underwent VATS lobectomy and four underwent lobectomy through a conventional open thoracotomy. One patient had open pneumonectomy. The median operating time (160 min in VATS lobectomy and 165 min in open lobectomy), median duration of chest tube drainage (4 days in VATS lobectomy and 6.5 days in open lobectomy), and postoperative complications (one patient in each treatment group) were similar between the VATS and open lobectomy groups. The hospital stay was shorter in the VATS lobectomy group (median 5 days) than in the open lobectomy group (median 7.5 days). No postoperative or procedure-related mortality occurred. CONCLUSIONS: CCAM is rare in adults. Patients usually present with recurrent respiratory infections and thin-walled multi-septated cystic lesions. VATS is a feasible and safe technique to treat adult patients with CCAM. PMID- 17344062 TI - Changes in body composition after childhood cancer treatment: impact on future health status--a review. AB - PURPOSE: To describe data on changes in body composition in childhood cancer survivors. Underlying mechanisms in development of obesity are addressed, in order to discuss intervention strategies. METHODS: A systematic literature search was undertaken with a number of search terms. RESULTS: Female survivors of ALL and brain tumours, especially if treated with cranial irradiation, showed a higher prevalence of obesity compared with the general population, while survivors of other malignancies had a higher prevalence of underweight. Influences of corticosteroid treatment and cytostatics on body composition are uncertain. Diminished physical activity, early adiposity rebound (<5 years of age) and/or hypothalamic involvement of tumour or treatment, and subsequent growth hormone deficiency, may play a role in the development of obesity in childhood cancer survivors. CONCLUSION: Longitudinal prospective studies in more extensive cohorts are necessary to estimate actual prevalence and facilitate the unravelling of the underlying mechanisms in change of body composition. PMID- 17344064 TI - Cellular sites of Drosophila NinaB and NinaD activity in vitamin A metabolism. AB - The Drosophila genes ninaB and ninaD, encoding a beta-carotene oxygenase and a type B scavenger receptor respectively, are essential for the biosynthesis of the 3-hydroxyretinal chromophore of rhodopsin. We analyzed transgenic reporter strains and performed in situ hybridization to show that both ninaB and ninaD are expressed in the adult brain but not retinal tissues. Developmental RT-PCR and tissue expression studies showed that ninaB is only expressed in the adult brain, while ninaD is expressed in the adult brain, the adult body, and many larval tissues. The data support a model in which NinaD is required for uptake and storage of dietary carotenoids throughout the larval and adult stages of development. Beta-carotene is transported to the adult brain, where cellular uptake by NinaD allows cleavage by the NinaB enzyme to produce retinal. Retinal is then transported to the retina for rhodopsin biogenesis. PMID- 17344063 TI - Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease. AB - Recessive mutations in GJA12/Cx47, the gene encoding the gap junction protein connexin47 (Cx47), cause Pelizaeus-Merzbacher-like disease (PMLD), which is characterized by severe CNS dysmyelination. Three missense PMLD mutations, P87S, Y269D and M283T, were expressed in communication-incompetent HeLa cells, and in each case the mutant proteins appeared to at least partially accumulate in the ER. Cells expressing each mutant did not pass Lucifer Yellow or neurobiotin in scrape loading assays, in contrast to robust transfer in cells expressing wild type Cx47. Dual whole-cell patch clamping of transfected Neuro2A cells demonstrated that none of the mutants formed functional channels, in contrast to wild type Cx47. Immunostaining sections of primate brains demonstrated that oligodendrocytes express Cx47, which is primarily localized to their cell bodies. Thus, the Cx47 mutants associated with PMLD likely disrupt the gap junction coupling between astrocytes and oligodendrocytes. PMID- 17344065 TI - In vivo exposure of clearnose skates, Raja eglanteria, to ionising X-radiation: acute effects on the peripheral blood, spleen, and epigonal and Leydig organs. AB - The effects of ionising radiation on the peripheral blood, spleen, and epigonal and Leydig organs of cartilaginous fishes were investigated using juvenile clearnose skates, Raja eglanteria. Skates (N = 80) were sacrificed 12 days after exposure to 0-75 Gy of X-radiation, and morphometrics (body mass, disc width, total length), mass of spleens and epigonal organs, and peripheral blood leucocyte (PBL) counts were compared to controls using ANOVA. Spleen and epigonal organ mass and PBL counts declined logarithmically as a function of radiation dose. To assess recovery from X-radiation, skates (N = 40) were exposed to 0, 9 or 18 Gy and sacrificed when moribund or on days 10, 20, 30 and 40 post irradiation. Partial recovery of Leydig organ and splenic red pulp was evident after 40 days in skates exposed to 9 Gy, but no indication of recovery was apparent at higher doses. Median lethal dose by 30 days (LD50/30) was calculated to be 9-18 Gy, similar to that determined for other fishes. PMID- 17344066 TI - Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants. AB - Infants born preterm have a high incidence of neurodevelopmental impairment in later childhood, often associated with poorly defined cerebral white matter abnormalities. Diffusion tensor imaging quantifies the diffusion of water within tissues and can assess microstructural abnormalities in the developing preterm brain. Tract-based spatial statistics (TBSS) is an automated observer-independent method of aligning fractional anisotropy (FA) images from multiple subjects to allow groupwise comparisons of diffusion tensor imaging data. We applied TBSS to test the hypothesis that preterm infants have reduced fractional anisotropy in specific regions of white matter compared to term-born controls. We studied 26 preterm infants with no evidence of focal lesions on conventional magnetic resonance imaging (MRI) at term equivalent age and 6 healthy term-born control infants. We found that the centrum semiovale, frontal white matter and the genu of the corpus callosum showed significantly lower FA in the preterm group. Infants born at less than or equal to 28 weeks gestational age (n=11) displayed additional reductions in FA in the external capsule, the posterior aspect of the posterior limb of the internal capsule and the isthmus and middle portion of the body of the corpus callosum. This study demonstrates that TBSS provides an observer-independent method of identifying white matter abnormalities in the preterm brain at term equivalent age in the absence of focal lesions. PMID- 17344067 TI - Quality of life among Brazilian children with epilepsy: validation of a parent proxy instrument (QVCE-50). AB - PURPOSE: To analyze the validity and reliability of an epilepsy specific health related quality of life (HRQL) instrument (QVCE-50), constructed for Brazilians. The QVCE-50 comprises the following domains: physical (9 items), psychological (18 items), social/familial (7 items), and cognitive/educational (16 items). Items were scored on a four point scale. Domains were equally weighted using percent scores. The questionnaire ends with a quality of life scale scored 0-10 and a space for free observations. METHODS: A total of 77 children with epilepsy were consecutively seen in a neuropaediatric ambulatory unit. Parents or caregivers responded to the QVCE-50 and a Portuguese version of ICIS (Impact of Childhood Illness Scale). QVCE-50 was analyzed for internal consistency, reliability, content and concurrent validity. Clinical and socio-demographic variables were also analyzed. RESULTS: Socio-demographic and clinical variables that differed in at least one domain were age, sex, time since diagnosis, epilepsy family history, and antiepileptic drug used. Internal consistency, analyzed by Cronbach's alpha, showed good results for total and domain scores: physical (0.68), psychological (0.86), socio-familiar (0.70) and cognitive educational (0.91). Total scores on the QVCE-50 and ICIS are inversely correlated (Pearson's r=-0.74, p<0.0001). The Intraclass Correlation Coefficients for test retest reliability were acceptable: physical (0.51), psychological (0.62), socio familiar (0.66), cognitive-educational (0.85) and total (0.77), p<0.0001. CONCLUSIONS: QVCE-50 has good psychometric properties. It is a useful tool for analyzing HRQL in children with epilepsy for Portuguese speakers, especially Brazilians. Other properties should be further tested, such as responsiveness to drug and surgical treatment, capacity of distinguishing among seizure control categories and etiology (with a larger sample) and impact of psychiatric and cognitive co-morbidities. PMID- 17344068 TI - The ratio of type II collagen breakdown to synthesis and its relationship with the progression of knee osteoarthritis. AB - OBJECTIVE: To examine whether the baseline ratio of a type II collagen breakdown marker to a synthesis marker, or the level of these markers individually, is associated with the likelihood of knee osteoarthritis (OA) progression between baseline and 18 months. METHODS: Participants were recruited from community sources and had knee OA. Blood was drawn at baseline. Collagen synthesis was measured by commercial enzyme-linked immunosorbent assay (ELISA) assay that detects c-propeptide of type II procollagen (CPII). Serum markers of collagenase cleavage of cartilage type II collagen [C2C epitope (COL2-3/4Clong mono) and C1,2C epitope (COL2-3/4Cshort)] were also assayed. Knee radiographs (semi-flexed with fluoro confirmation) were obtained at baseline and 18 months. OA progression was examined using worsening of joint space grade and worsening of Kellgren/Lawrence grade. The relationship between baseline serum markers and subsequent progression was analyzed from logistic regression. RESULTS: Baseline levels of these markers, considered individually, were not associated with a change in the odds of progression. Belonging to the low synthesis tertile was associated with a greater likelihood of progression, approaching significance (adjusted odds ratio [OR] 1.86, 95% confidence interval [CI] 0.96, 3.63). A greater C2C:CPII ratio and C1,2C:CPII ratio were each associated with an increase in the odds of joint space grade progression, which approached significance (e.g., adjusted OR of C2C:CPII ratio was 3.15, 95% CI 0.91, 10.85). CONCLUSION: While the degradation markers individually, considered as continuous variables, did not predict OA progression, belonging to the lower synthesis marker tertile and greater degradation/synthesis marker ratios were associated with an elevation in the odds of progression albeit not achieving significance. PMID- 17344069 TI - Changes in pain, stiffness and physical function in patients with osteoarthritis waiting for hip or knee joint replacement surgery. AB - OBJECTIVE: Little has been reported on changes in health status in patients with osteoarthritis (OA) while waiting for hip or knee replacement surgery. In this study we assessed (1) changes in self-reported pain, stiffness and physical function in patients with OA of the hip or knee, from the decision to undergo surgery to 14 days prior to surgery, and (2) the determinants of these changes. METHODS: Among 353 baseline respondents, 170 waited >30 days for surgery, completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) before surgery and were included in the analysis of changes; 120 with OA of the hip and 50 of the knee. We analyzed changes in WOMAC scores using the paired t test and determinants of the changes using multiple linear regression. RESULTS: Patients with OA of the hip did not change on any WOMAC scale before surgery. Knee patients deteriorated with time on the WOMAC stiffness and total scales, but not on the pain or physical function subscales. In both patient categories, higher baseline WOMAC scores were associated with smaller changes on all subscales and the total score, and female sex was associated with deterioration on the pain subscale. CONCLUSIONS: Patients with OA of the hip reported no change in pain, stiffness or physical function while waiting for joint replacement surgery, whereas patients with OA of the knee deteriorated on the stiffness and total scales of the WOMAC. This suggests a difference in patient selection, referral pattern or disease development between the patient categories. PMID- 17344070 TI - Human insulin receptor juxtamembrane domain independent insulin signaling. AB - The exon 16-encoded juxtamembrane (JM) domain of human insulin receptor (hIR) harbors the NPEY motif which couples the insulin-activated hIR kinase to downstream signal transduction molecules. We sought to determine if signal transduction requires the entire exon 16-encoded 22-amino acid JM domain. Transfected CHO cells were generated stably expressing either the wild-type hIR (hIR-WT) or two mutant hIRs (hIRDeltaEx16 in which the JM domain was deleted, and hIRrosJM in which the deleted segment was replaced by the corresponding domain of v-ros protein). The mutant hIRDeltaEx16 and hIRrosJM exhibited similar insulin binding as the hIRWT. Insulin internalization and insulin dose-response experiments toward activation of downstream signal transduction molecules demonstrated that: i) the presence of intact hIR-JM domain which harbors the NPEY motif is essential for Shc phosphorylation but not for IRS-1 phosphorylation; ii) insulin signal transduction can occur independent of the JM domain of hIR and without participation of the NPEY motif; iii) engagement of this putative alternative downstream signal transduction is Shc independent and is dependent on insulin concentration; and iv) insulin internalization does not necessarily require the hIR specific aa sequence of the JM domain which can be partially substituted by the JM domain of the v-ros tyrosine kinase. PMID- 17344071 TI - A polysaccharide of the marine alga Capsosiphon fulvescens induces apoptosis in AGS gastric cancer cells via an IGF-IR-mediated PI3K/Akt pathway. AB - Because seaweed extracts have recently been found to have antioxidant and anti tumor activities, we analyzed a hot-water-soluble polysaccharide (PS) of the marine alga Capsosiphon fulvescens for its potential as a functional foodstuff by determining its effects on cell growth and DNA synthesis. MTS assays showed that the C. fulvescens PS (Cf-PS) significantly inhibited the proliferation of cultured human cancer cells in a dose-dependent manner. Cf-PS-treated AGS cells exhibited a marked increase in caspase-3 activation and a decrease in Bcl-2 expression. In addition, phosphorylation of insulin-like growth factor-I receptor (IGF-IR) was decreased in Cf-PS-treated AGS cells as compared to non-treated control cells, which is consistent with PI3-kinase (PI3K)/Akt activation. Cf-PS also decreased IGF-I-stimulated recruitment of p85 to IGF-IR and IRS-1. These results indicate that Cf-PS inhibits cell proliferation and induces apoptosis by inhibiting IGF-IR signaling and the PI3K/Akt pathway. PMID- 17344072 TI - Lipopolysaccharide regulates toll-like receptor 4 expression in human aortic smooth muscle cells. AB - Lipopolysaccharide (LPS) is a potent activator of cells of the immune and inflammatory systems, including macrophages, monocytes, and endothelial cells (EC). Toll-like receptor 4 (TLR4) has been identified as the primary receptor for LPS. Vascular smooth muscle cells (VSMCs) likely contribute significantly to the inflammation induced by low-level LPS in patients who are at risk for atherosclerosis. Previous study indicated that functional TLR4 was present in VSMCs. However, it remains unclear whether low levels of commercial LPS preparations can affect TLR4 expression in early stage. Here Real-time quantitative PCR analysis was used to detect TLR4 mRNA expression; Immunofluorescence, Western blot analysis and flow cytometry were used to examine TLR4 protein expression. It was shown that TLR4 was present in Human Aortic Smooth Muscle Cells (HASMCs). LPS can up-regulate TLR4 mRNA and protein expression in HASMCs in dose- and time-dependent manner. These data indicate that LPS regulate TLR4 expression in HASMCs. PMID- 17344073 TI - Trauma to erythrocytes induced by long term in vitro pumping using a roller pump. AB - The objective of this study is to investigate the impact of trauma on erythrocyte caused by long term in vitro pumping using roller pump. Ten bags of human blood (400 ml each) were provided by a local blood bank and they were divided into two groups with five bags in each group. Each blood bag was subject to pumping in a closed circuit, which was composed of silica gel tubes and a roller pump. Polystan and COBE pumps were used for the two groups, respectively. The blood was pumped for 16 h in vitro. Free hemoglobin (FHb), platelets (PLT), erythrocyte fragility (EF), and morphological analysis of erythrocytes observed under scanning electron microscope were measured to evaluate the impact of trauma on erythrocytes. A small amount of blood was collected for analysis before pumping, at the end of the 4th hour and then every 2 h till the end of the 16th hour. Some blood samples were also collected for electron microscope scanning before pumping and every 4 h during pumping. It was found that FHb and PLT linearly increased with the pumping time. There was a significant correlation between the two parameters (r=0.7745, p<0.001). The hemolysis indexes of the two groups were 0.296 and 0.3993 mg/L/h, respectively, with no significant difference. During the pumping process, EF changed slightly. The observation of scanning electron microscopy showed various deformed erythrocytes after pumping, including the distortion of cell membrane and the appearance of echinocytes, which increased with pumping time. This study demonstrated that long term pumping using roller pump not only caused the immediate rupture of red blood cells, i.e. the immediate hemolysis, but also caused sub-trauma to a large number of erythrocytes, which led to the delayed hemolysis. The change of erythrocyte morphology was the basis of the delayed hemolysis. PMID- 17344074 TI - Significance of IgG4 in the diagnosis of mucous membrane pemphigoid. AB - OBJECTIVE: To determine the diagnostic value and frequency of tissue deposition of IgG4 in comparison to polyclonal IgG, IgA, IgM, and C3. STUDY DESIGN: Oral mucosal biopsies of 82 patients clinically suspected to have mucous membrane pemphigoid (MMP) were analyzed by direct immunofluorescence (IF) using polyclonal anti-human IgG, IgM, IgA, fibrin, complement C3, and anti-human IgG4 subclass monoclonal antibodies. RESULTS: Based on clinical, hematoxylin and eosin (H & E), and direct IF studies, 34 cases were diagnosed as MMP. The most common antibody deposited was IgG (90%), followed by C3 (82%), and IgG4 (71%). In more than half the cases of MMP, IgG4 deposition was seen in combination with IgG and or C3. Strikingly, IgG4 was the sole antibody detected in 2 cases (6%). CONCLUSION: Our results suggest that the use of monoclonal IgG4 is important in the diagnosis of MMP. We suggest adding monoclonal IgG4 to the routine panel of antibodies used in studies of cases suspected to have MMP to avoid false-negatives. PMID- 17344075 TI - Erythema multiforme and related disorders. AB - Erythema multiforme (EM) and related disorders comprise a group of mucocutaneous disorders characterized by variable degrees of mucosal and cutaneous blistering and ulceration that occasionally can give rise to systemic upset and possibly compromise life. The clinical classification of these disorders has often been variable, thus making definitive diagnosis sometimes difficult. Despite being often caused by, or at least associated with, infection or drug therapy, the pathogenic mechanisms of these disorders remain unclear, and as a consequence, there are no evidence-based, reliably effective therapies. The present article reviews aspects of EM and related disorders of relevance to oral medicine clinical practice and highlights the associated potential etiologic agents, pathogenic mechanisms and therapies. PMID- 17344076 TI - Vascular endothelial growth factor family of ligands and receptors: review. AB - VEGF signaling often represents a critical rate-limiting step in physiological angiogenesis. The VEGF family comprises seven secreted glycoproteins that are designated VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, placental growth factor (PlGF) and VEGF-F. The VEGF family members bind their cognate receptors. The receptors identified so far are designated VEGFR-1, VEGFR-2, VEGFR-3 and the neuropilins (NP-1 and NP-2). We review in this article the biology of the VEGF ligands and the receptors. PMID- 17344077 TI - Bio-control by wildlife vaccination: a unique set of opportunities and challenges. PMID- 17344078 TI - Cancer--blame it all on viruses! Bladder tumours in cattle and sarcoids in horses may help us understand the relationship between some cancers and viruses. PMID- 17344079 TI - Surgical treatment of capillary hemangiomas causing amblyopia. AB - BACKGROUND: Capillary hemangiomas of the eyelids and orbit can cause refractive and occlusive amblyopia. Although oral and intralesional steroid injections are the most common treatment modalities, sometimes they are not successful. There is a paucity of information in the literature on the success of eliminating amblyogenic factors by treating these lesions with surgical resection. METHODS: Retrospective chart review of 10 patients in two pediatric ophthalmology practices who underwent surgical excision of a capillary hemangioma that was causing amblyopia and that had failed to regress with other treatment. RESULTS: Two patients had surgery secondary to pupillary occlusion, which was successful in relieving occlusion. Eight patients had surgery secondary to significant astigmatism. The average preoperative astigmatic difference between the affected and unaffected eye in five of these patients undergoing surgery before the age of 21 months was 2.15 D. The average postoperative astigmatic difference was 0.1 D. The average preoperative astigmatic difference between the affected and unaffected eye in three patients undergoing surgery after 21 months of age was 1.6 D. Surgery completely failed to reduce the astigmatism in two of these patients. The third patient had a decrease of 0.75 D of cylinder but still had a difference of 1.75 D between the two eyes postoperatively. Postoperative complications in this study included wound infection in one patient. CONCLUSIONS: Surgical excision of capillary hemangiomas that were resistant to other modes of treatment was useful in relieving pupillary occlusion and in decreasing the amount of astigmatism if performed before the age of 21 months in our series of patients. Our cases as well as the literature suggest that surgery should be performed at 13 months or earlier to reduce the amount of astigmatism. PMID- 17344080 TI - Cost of venom regeneration in Parabuthus transvaalicus (Arachnida: Buthidae). AB - Scorpion venom has many components, but is mainly made up of water, salts, small molecules, peptides, and proteins. One can reasonably assume that the production and storage of this complex secretion is an expensive metabolic investment. However, to date, no study has addressed the costs associated with the regeneration of venom by scorpions. Using a closed-system respirometer, we examined the difference in oxygen consumption between milked and unmilked scorpions to determine the metabolic costs associated with the first 72 h of subsequent venom synthesis. During this time period, milked scorpions had a significantly higher (39%) metabolic rate than unmilked scorpions. The regenerated venom from a second milking had significantly lower (74%) protein concentration, suggesting that venom regeneration was incomplete after 72 h. The protein content in the regenerated venom was not correlated with oxygen consumption. The significant increase in oxygen consumption after milking supports existing hypotheses about the metabolic cost associated with venom regeneration and provides further insight on why scorpions appear to be judicious in their stinger use. PMID- 17344081 TI - Chloride inhibition of nitrite uptake for non-teleost Actinopterygiian fishes. AB - Fish that transport environmental chloride with a gill uptake mechanism (gill epithelial Cl(-)/HCO(3)(-)cotransport exchange system), also transport nitrite into plasma through the same mechanism. Because of the relationship between nitrite uptake and the gill chloride uptake mechanism, nitrite uptake can provide insight regarding the method of chloride uptake for fish. This study was designed to determine if non-teleost fishes concentrate nitrite in their plasma, and to determine if chloride inhibits nitrite uptake in non-teleost fish. To determine if bowfin Amia calva, spotted gar Lepisosteus oculatus, alligator gar Atractosteus spatula, and paddlefish Polyodon spathula concentrate environmental nitrite in their plasma, individuals were exposed to concentrations of 0, 1, 10, or 100 mg/L nitrite-N. After exposure, all species had plasma nitrite-N concentrations greater than environmental levels. To determine if chloride inhibits nitrite uptake for spotted gar, alligator gar, and paddlefish, fish were exposed to 1 mg/L nitrite-N and 20 mg/L chloride as calcium chloride, or to 1 mg/L nitrite-N only. Chloride effectively prevented nitrite from being concentrated in the plasma of all species. It appears that non-teleost fish concentrate nitrite in their plasma via their chloride uptake mechanism and that this is an ancestral characteristic for teleost. PMID- 17344082 TI - Recombinant eggshell ovocalyxin-32: expression, purification and biological activity of the glutathione S-transferase fusion protein. AB - The avian eggshell is a highly ordered biomineral composed mainly of calcium carbonate associated with an organic matrix composed of proteins, glycoproteins and proteoglycans. This structure provides the developing embryo with protection from physical damage and microbial invasion. Ovocalyxin-32 (OCX-32) is a 32 kDa eggshell-specific matrix protein which has been cloned and demonstrates 30% identity with the mammalian carboxypeptidase inhibitor, latexin. In order to further study its function, recombinant OCX-32 protein was expressed in E. coli. The protein was extracted from inclusion bodies and purified by sequential DEAE Sepharose and Ni2+ metal ion affinity chromatographies as a 58 kDa GST-fusion protein. The refolded GST-OCX-32 significantly inhibited bovine carboxypeptidase and also inhibited the growth of Bacillus subtilis. The results suggest that OCX 32 may show similar activity to the fusion protein and reinforce the antimicrobial properties of the eggshell by providing protection to the developing avian embryo. OCX-32 is the first example of an eggshell specific protein to be successfully cloned and expressed in a prokaryotic system. The association of an antimicrobial protease inhibitor with the outer eggshell and cuticle of the table egg may enhance the food safety of this product. PMID- 17344083 TI - Serum alpha1-acid glycoprotein (AGP) concentration in non-symptomatic cats with feline coronavirus (FCoV) infection. AB - Previous studies have demonstrated that the concentration of alpha1-acid glycoprotein (AGP) transiently increases in asymptomatic cats infected with feline coronavirus (FCoV). In order to establish whether these fluctuations depend on the FCoV status, the serum concentration of AGP and anti-FCoV antibody titres and/or faecal shedding of FCoVs in clinically healthy cats from catteries with different levels of prevalence of FCoV infection were monitored over time. Serum AGP concentrations fluctuated over time in clinically healthy cats from the cattery with the highest prevalence of feline infectious peritonitis (FIP) and significantly increased just before an outbreak of FIP. Further studies are required to clarify whether the observed increase of AGP concentration is a consequence of the increased viral burden or a protective response against mutated viral strains. Nevertheless, the results of the present study suggest that AGP might be useful in monitoring FCoV-host interactions in FCoV-endemic catteries. PMID- 17344084 TI - Osteoarticular complications of brucellosis in Hamedan, an endemic area in the west of Iran. AB - OBJECTIVE: To determine the frequency and clinical characteristics of osteoarticular complications of brucellosis in an endemic region in Iran. METHODS: In a prospective study we evaluated 245 patients with brucellosis diagnosed between January 2004 and December 2005. Patients included were those older than 8 years of age and who had clinical features suggestive of brucellosis and specific antibodies at significant titers, and/or positive blood or body fluid culture for Brucella species. A bone scan was performed in those with a clinical suspicion of osteoarticular involvement. RESULTS: Seventy patients (28.6%) had osteoarticular complications. Sacroiliitis was the most common complication (75.7%), followed by spondylitis (21.4%) and peripheral arthritis (8.6%). Spondylitis was the most common osteoarticular complication in the elderly. Relapses occurred in five (2%) patients, three of them with spondylitis. CONCLUSIONS: Osteoarticular disease is the most common complication of brucellosis in Western Iran. Sacroiliitis is the most common form of osteoarticular complication. With the use of a proper treatment regimen, the prospect for recovery is good. PMID- 17344085 TI - Radiculopathy as a manifestation of Langerhans' cell histiocytosis. AB - Langerhans' cell histiocytosis (LCH) is a rare condition of children and young adults in which Langerhans' cells proliferate. The clinical spectrum ranges from solitary or few focal lesions to multisystem involvement mimicking vasculitis or hematological malignancy. Focal bone lesions, known as eosinophilic granulomas, are the most common manifestations. Eosinophilic granuloma usually presents with a variable combination of pain, swelling, fracture, and fever. Facial bone involvement may manifest as an ear discharge, hearing loss, or exophthalmos. Nerve root pain is rarely reported, even in patients with lesions in the axial skeleton. We report four cases of nerve root pain caused by LCH. Two male patients aged 25 and 34 years, respectively, presented with truncated femoral neuralgia related to acetabular granulomas. A 25-year-old woman with involvement of the L5 vertebral body and a 41-year-old man with a sacral lesion presented with sciatica. PMID- 17344086 TI - [Risk factors for group B streptococcal colonization in pregnant women at term: prospective study of 294 cases]. AB - OBJECTIVE: To determine the rate and risk factors for group B streptococcus (GBS) colonization in term pregnancies. PATIENTS AND METHODS: Vaginal and anal cultures were prospectively conducted in 294 parturient on admission for term vaginal delivery. RESULTS: Thirty-eight (12.92%) parturient had positive GBS cultures. None of the studied risk factors (age, education status, nulliparity, previous obstetric problem, twin pregnancy and diabetes) was statistically predictive of maternal colonization. All the isolated GBS were sensitive to the penicillin G. DISCUSSION AND CONCLUSION: Systematic screening strategy of GBS close to the delivery on all pregnant women is desirable. PMID- 17344087 TI - [Ductal carcinoma in situ of the breast with microinvasion. Role of sentinel lymph node biopsy]. AB - OBJECTIVES: To investigate the role of sentinel lymph node biopsy for microinvasive ductal carcinoma in situ of the breast. PATIENTS AND METHODS: From January 2001 to January 2006, lymphatic mapping was performed using radiocolloid and/or blue dye technique. Full axillary lymph node dissection was accomplished systematically in 10 instances at the beginning of the study, and furthermore when the sentinel node was involved (macrometastatic or micrometastatic disease). RESULTS: Identification rate was 98% (40/41), the unsuccessful procedure occurred after incisional biopsy for diagnosis. The number of sentinel nodes removed was 2 in average (1-5). Sentinel node involvement was found in 10% of cases (4/40): 1 sentinel node macrometastasis pN1, 2 sentinel node micrometastases determined by hematoxylin and eosin staining pN1 (mi), 1 sentinel node micrometastasis detected only by immunohistochemical staining pN0 (mi). DISCUSSION AND CONCLUSION: Sentinel lymph node sampling should not be currently applied for management of every ductal carcinoma in situ of the breast but a selective utilization is proposed in documented high risk subset of patients according to clinical, mammographic, and histologic features obtained by percutaneous biopsies. Ductal carcinoma in situ (DCIS) with proved or suspected microinvasion could be scheduled for sentinel node procedure a fortiori in cases undergoing mastectomy because of extensive DCIS before the occurrence of disturbances of lymphatic drainage induced by surgical breast dissection. PMID- 17344088 TI - Characterisation of a bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) from Drosophila melanogaster. AB - The intracellular functions of diadenosine polyphosphates are still poorly defined. To understand these better, we have expressed and characterized a heat stable, 16.6kDa Nudix hydrolase (Apf) that specifically metabolizes these nucleotides from a Drosophila melanogaster cDNA. Apf always produces an NTP product, with substrate preference depending on pH and divalent ion (Zn(2+) or Mg(2+)). For example, diadenosine tetraphosphate is hydrolysed to ATP and AMP with K(m), k(cat) and k(cat)/K(m) values 9microM, 43s(-1) and 4.8microM(-1)s(-1) (pH 6.5, 0.1mMZn(2+)) and 12microM, 13s(-1) and 1.1microM(-1)s(-1) (pH 7.5, 20mMMg(2+)), respectively. However, diadenosine hexaphosphate is efficiently hydrolysed to ATP only at pH 7.5 with 20mMMg(2+) (K(m), k(cat) and k(cat)/K(m) values of 15microM 4.0s(-1), and 0.27microM(-1)s(-1)). Fluoride potently inhibits diadenosine tetraphosphate hydrolysis in the presence of Mg(2+) (IC(50)=20microM), whereas it is ineffective in the presence of Zn(2+), supporting the view that inhibition involves a specific, MgF(3)(-)-containing transition state analogue complex. Patterns of Apf expression in Drosophila tissues show Apf mRNA levels to be highest in embryos and adult females. Subcellular localization with Apf-EGFP fusion constructs reveals Apf to be predominantly nuclear, having an apparent preferential association with euchromatin and facultative heterochromatin. This supports a nuclear function for diadenosine tetraphosphate. Our results show Apf to be a fairly typical member of the bis (5'-nucleosyl)-tetraphosphatase subfamily of Nudix hydrolases with features that distinguish it from a previously reported bis (5'-nucleosyl) tetraphosphatase hydrolase activity from Drosophila embryos. PMID- 17344089 TI - Modulation of immunological synapse by membrane-bound and soluble ligands. AB - An efficient adaptive immune response should prevent pathogen infections and tumor growth without causing significant damage to host constituents. A crucial event determining the balance between tolerance and immunity is antigen recognition by T cells on the surface of antigen presenting cells (APC). Several molecular contacts at the interface between T cells and APCs contribute to define the nature of the adaptive immune response against a particular antigen. Upon TCR engagement by a peptide-MHC complex (pMHC) on the surface of an APC, a specialized supra-molecular structure known as immunological synapse (IS) assembles at the interface between these two cells. This structure involves massive re-distribution of membrane proteins, including TCR and pMHC complexes, as well as co-stimulatory and adhesion molecules. Furthermore, IS assembly leads to several important intracellular events necessary for T cell activation, such as recruitment of signaling molecules and cytoskeleton rearrangements. Because IS assembly leads to major consequences on the function of T cells, several studies have attempted to identify both soluble and membrane-bound molecules that could contribute to modulate the IS function. Here we describe recent literature on the regulation of IS assembly and modulation by TCR/pMHC binding kinetics, chemokines and cytokines focusing on their role at controlling the balance between adaptive immunity and tolerance. PMID- 17344090 TI - Integrating simulation and theory of mind: from self to social cognition. PMID- 17344091 TI - Assessment of the genotoxicity in toad Bufo raddei exposed to petrochemical contaminants in Lanzhou Region, China. AB - Single cell gel electrophoresis or comet assay, micronucleus (MN) test and global DNA methylation detection were used to assess the genotoxicity in toad Bufo raddei exposed to the petrochemical (mainly oil and phenol) polluted area in Lanzhou Region (LZR) comparing with a relatively unpolluted area in Liujiaxia Region (LJXR). The results from the present study indicated that DNA damage and MN frequency in toad from LZR were significantly higher than those from LJXR at the same sampling month, whereas the degree of global DNA methylation was lower, which implies that the petrochemical contaminants at environmental level in LZR were genotoxic to B. raddei. The degree of genotoxic damage was obviously related with the extent of pollution among the three sampling months in LZR. The significantly positive correlations between DNA damage and concentrations of oil and/or phenol existed in liver cells but erythrocytes, implying that liver is more suitable as a sentinel tissue for the assessment of genotoxic impact of low level contamination. The results from both comet assay and global DNA methylation detection on liver cells showed that the genotoxicity varied significantly with oil and/or phenol concentrations, suggesting that these two methods are relatively sensitive and suitable for monitoring the genotoxicity of petrochemical pollutants on amphibians. PMID- 17344092 TI - An Internet supported workflow for the publication process in UMVF (French Virtual Medical University). AB - The " Universite Medicale Virtuelle Francophone" (UMVF) is a federation of French medical schools. Its main goal is to share the production and use of pedagogic medical resources generated by academic medical teachers. We developed an Open Source application based upon a workflow system, which provides an improved publication process for the UMVF. For teachers, the tool permits easy and efficient upload of new educational resources. For web masters it provides a mechanism to easily locate and validate the resources. For librarian it provide a way to improve the efficiency of indexation. For all, the utility provides a workflow system to control the publication process. On the students side, the application improves the value of the UMVF repository by facilitating the publication of new resources and by providing an easy way to find a detailed description of a resource and to check any resource from the UMVF to ascertain its quality and integrity, even if the resource is an old deprecated version. The server tier of the application is used to implement the main workflow functionalities and is deployed on certified UMVF servers using the PHP language, an LDAP directory and an SQL database. The client tier of the application provides both the workflow and the search and check functionalities. A unique signature for each resource, was needed to provide security functionality and is implemented using a Digest algorithm. The testing performed by Rennes and Lille verified the functionality and conformity with our specifications. PMID- 17344093 TI - Fully automated quantification of hepatitis C virus (HCV) RNA in human plasma and human serum by the COBAS AmpliPrep/COBAS TaqMan system. AB - BACKGROUND: HCV RNA is commonly recognized as key parameter for reliable diagnosis and treatment monitoring of HCV infection. Determination of blood HCV RNA concentrations reduces the pre-seroconversion period in the diagnosis of HCV infection and supports management of interferon alpha-based therapies of chronic HCV infection. OBJECTIVES AND STUDY DESIGN: The COBAS AmpliPrep/COBAS TaqMan HCV Test combines automated extraction of nucleic acids on the COBAS AmpliPrep Instrument with real-time PCR on the COBAS TaqMan Analyzer, thus greatly reducing hands-on time during sample preparation and amplification/detection. The test, which is calibrated to the 1st International HCV WHO Standard, was evaluated for sensitivity, dynamic range, precision, matrix equivalence, genotype inclusivity, interfering substances, diagnostic and analytical specificity, as well as for correlation with two other commercial tests for HCV RNA quantification. RESULTS: The COBAS AmpliPrep/COBAS TaqMan HCV Test demonstrated a >6-log dynamic range of 43-6.90 E+7 IU/mL, a sensitivity (95% hit rate) of at least 15 IU/mL for HCV WHO Standard and a comparable quantification of genotypes 1-6. HCV quantification results were in good correlation with those obtained by the COBAS AMPLICOR HCV MONITOR Test v2.0 and the VERSANT HCV RNA 3.0 test. CONCLUSIONS: The fully automated COBAS AmpliPrep/COBAS TaqMan HCV Test excellently accomplishes the requirements for highly sensitive detection and reliable quantification of HCV in clinical samples and thus improves therapy monitoring and management of HCV infection. PMID- 17344095 TI - Online integrated solution to collect data, generate information and manage events in the human biomonitoring field. AB - In the ambit of Work Package 1 of the ESBIO Project, an online integrated solution to collect data, to generate information, and to manage mainly information-sharing events related with human biomonitoring within Europe has been designed and is being implemented. The present paper summarises the methodological approaches used by the authors as proposers, general promoters and disseminators of this strategic concept, as well as the first outcomes and future actions to be taken, in the short and longer term, to face present and future challenges to make this innovative solution happen. PMID- 17344094 TI - Activation of cytosolic phospholipase A2 and 15-lipoxygenase by oxidized low density lipoproteins in cultured human lung fibroblasts. AB - In cell cultures of human lung fibroblasts, we found that oxidized LDL (oxLDL), after 24-h treatment, stimulated arachidonic acid release. A putative role for phospholipases A(2) and MAPK activities in this process was postulated. Consequently, we studied the contribution of either Ca(2+)-dependent, cytosolic phospholipase A(2) (cPLA(2)) or Ca(2+)-independent phospholipase A(2) (iPLA(2)), and the role of the MAP kinase family in oxLDL toxicity to fibroblastic cells in vitro. Activation of extracellular signal-regulated kinases ERK1/2, p38 and c-Jun NH(2)-terminal kinase (JNK) was also assessed with Western blotting. Compared with cellular samples untreated or treated with native LDL, treatment with oxLDL (50-100 microM hydroperoxides) for 24 h significantly increased the levels of either cPLA(2) protein expression or constitutively phosphorylated cPLA(2) protein; in addition we observed enzyme translocation to membranes. iPLA(2) activity was not stimulated by oxLDL. Arachidonic acid release appeared to be associated with phosphorylation of ERK1/2 which was significantly enhanced in a dose-dependent manner whereas no activation of p38 and JNKs was found, indicating that these MAPKs are not involved in mediating the maximal oxLDL response. Western blotting on subcellular fractions and confocal microscopy analyses confirmed an increase in 15-lipoxygenase (15-LO) protein expression and translocation upon activation. A significant increase of cyclooxygenase-2 expression into membrane fraction was also found. Collectively, the data presented link the stimulation of ERK-cPLA(2)-15-LO pathway by oxLDL to the prooxidant mechanism of the lipoprotein complex. It may initially stimulate the fibroblast reaction against the oxidation challenge as well as metabolic repair, such as during lung inflammation and pulmonary fibrosis. PMID- 17344096 TI - Abeta, tau and ApoE4 in Alzheimer's disease: the axonal connection. AB - Mutations in amyloid precursor protein (APP), tau and apolipoprotein E4 (ApoE4) lead to Alzheimer's disease (AD) or related pathologies. Pathogenesis and interactions between these pathways have been studied in mouse models. Here, we highlight the fact that axons are important sites of cellular pathology in each pathway and propose that pathway convergence at the molecular level might occur in axons. Recent developments suggest that axonal transport of APP influences beta-amyloid deposition and that tau regulates axonal transport. ApoE4 influences both axonal tau phosphorylation and amyloid-induced neurite pathology. Thus, a better understanding of axonal events in AD might help connect the pathogenic mechanisms of beta-amyloid, ApoE4 and tau, indicating the most important steps for therapeutic targeting. PMID- 17344097 TI - Novel aspects of vitamin C: how important is glypican-1 recycling? AB - The reduced form of vitamin C, ascorbic acid, is well known for its function as an antioxidant and as a protective agent against scurvy. However, many recent studies indicate other functions for vitamin C in mammalian cells. Novel findings provide possible explanations for observed beneficial effects of a high intake of vitamin C on cell growth, gene transcription, host resistance to infection, uptake of polyamines and clearance of misfolded proteins. Vitamin C exerts its effects indirectly via hypoxia-inducible factor, nitric oxide synthase and the heparan sulfate proteoglycan glypican-1, which is deglycanated in a vitamin C- and copper-dependent reaction. PMID- 17344098 TI - Intracardiac metastasis of malignant melanoma. AB - Aim To report a case of intracardiac metastasis of malignant melanoma with multiple mobile, large masses in left atrium (LA), left ventricle (LV) and right atrium (RA). PMID- 17344099 TI - A dancing thrombus in the right atrium going hand-in-hand with the electrocardiogram. AB - A 69-year old male with a large pulmonary embolism is described before and after thrombolytic treatment. The echocardiographic and electrocardiographic hallmarks of right ventricular pressure overload and dilatation are illustrated. PMID- 17344100 TI - The classification of neuropsychiatric disorders in epilepsy: a proposal by the ILAE Commission on Psychobiology of Epilepsy. AB - The classification of psychiatric disorders in epilepsy has evolved considerably from the first attempts in the 19th century. A dedicated subcommission of the ILAE Commission on Psychobiology of Epilepsy (now the Commission on Neuropsychiatric Aspects) has developed this classification proposal. The aim of this proposal is to separate disorders comorbid with epilepsy and those that reflect ongoing epileptiform activity from epilepsy-specific disorders, and to attempt to subclassify the epilepsy-specific disorders alone. Further, the classification of epilepsy-specific psychiatric disorders has largely followed their relationship to the ictus, with factors such as relationship to antiepileptic drug (AED) change being coded as additional information. Finally, this proposal presents a clinical and descriptive system of classification rather than an etiological classification on the grounds that there is currently inadequate information for the latter approach to be employed globally. PMID- 17344101 TI - Modulation of xenobiotic biotransformation system and hormonal responses in Atlantic salmon (Salmo salar) after exposure to tributyltin (TBT). AB - Multiple biological effects of tributyltin (TBT) on juvenile salmon have been investigated. Fish were exposed for 7 days to waterborne TBT at nominal concentrations of 50 and 250 microg/L dissolved in dimethyl sulfoxide (DMSO). Hepatic samples were analyzed for gene expression patterns in the hormonal and xenobiotic biotransformation pathways using validated real-time PCR method. Immunochemical and several cytochrome P450 (CYP)-mediated enzyme activity (ethoxyresorufin: EROD, benzyloxyresorufin: BROD, methoxyresorufin: MROD and pentoxyresorufin: PROD) assays were analyzed. Our data show that TBT produced concentration-specific decrease of estrogen receptor-alpha (ERalpha), vitellogenin (Vtg), zona radiata protein (Zr-protein) and increase of estrogen receptor-beta (ERbeta) and androgen receptor-beta (ARbeta) in the hormonal pathway. In the xenobiotic biotransformation pathway, TBT produced apparent increase and decrease at respective low and high concentration, on aryl hydrocarbon receptor-alpha (AhRalpha), AhR nuclear translocator (ARNT) and AhR repressor (AhRR) mRNA. The expression of CYP1A1 and GST showed a TBT concentration-dependent decrease. The AhRbeta, CYP3A and uridine diphosphoglucuronosyl transferase (UGT) mRNA expressions were significantly induced after exposure to TBT. Immunochemical analysis of CYP3A and CYP1A1 protein levels confirmed the TBT effects observed at the transcriptional levels. The effect of TBT on the biotransformation enzyme gene expressions partially co related but did not directly parallel enzyme activity levels for EROD, BROD, MROD and PROD. In general, these findings confirm previous reports on the endocrine effects of TBT, in addition to effects on hepatic CYP1A isoenzyme at the transcriptional level that transcends to protein and enzymatic levels. The induced expression patterns of CYP3A and UGT mRNA after TBT exposure, suggest the involvement of CYP3A and UGT in TBT metabolism in fish. The effect of TBT on CYP3A is proposed to represent another hormonal effect of TBT not previously reported in any fish or lower vertebrate. The proposed androgenic effect is supported by the observation that TBT also induced ARbeta mRNA expression in a concentration-specific manner. To our knowledge, this is the first study that has simultaneously studied multiple responses after exposure to TBT in fish. PMID- 17344102 TI - Effects of alkylphenols on glycerophospholipids and cholesterol in liver and brain from female Atlantic cod (Gadus morhua). AB - Offshore oil production releases large amounts of lipophilic compounds in produced water into the ocean. In 2004, 143 million m(3) produced water, containing approximately 13 tons of long-chain (>C(4)) alkylphenols (AP), was discharged from installations in the Norwegian sector of the North Sea. Long chain APs are known to cause endocrine disruption in a number of species. However, relatively little is known about their long-term effects in the marine environment. In the present study, Atlantic cod (Gadus morhua) were exposed (0.02 to 80 mg AP/kg) to a mixture (1:1:1:1) of APs (4-tert-butylphenol, 4-n pentylphenol, 4-n-hexylphenol and 4-n-heptylphenol) or 17 beta-estradiol (5 mg E2/kg) for 5 weeks and the effect on the fatty acid profile and cholesterol content in the membrane lipids from the liver and the brain was studied. We also determined the interaction between different para-substituted APs and glycerophospholipids (native phospholipids extracted from cod liver and brain) and model phosphatidylcholine (PC 16:0/22:6 n-3) in monolayers with the Langmuir Blodget technique. The study demonstrated that APs and E2 alter the fatty acid profile in the polar lipids (PL) from the liver to contain more saturated fatty acids (SFA) and less n-3 polyunsaturated fatty acids (n-3 PUFA) compared with control. In the brain of the exposed groups a similar effect was demonstrated, although with higher saturation of the fatty acids found in the neutral lipids (mainly cholesterol ester), but not in the polar lipids. The AP and E2 exposure also gave a decline in the cholesterol levels in the brain. The in vitro studies showed that APs increased the mean molecular areas of the PLs in the monolayers at concentrations down to 5 microM, most likely due to intercalation of the APs between PL molecules. The increase in molecular area increased with the length of the alkyl side chain. PMID- 17344103 TI - Characterization of Bcor expression in mouse development. AB - Mutation of the gene encoding the transcriptional corepressor BCOR results in the X-linked disorder Oculofaciocardiodental syndrome (OFCD or MCOPS2). Female OFCD patients suffer from severe ocular, craniofacial, cardiac, and digital developmental defects and males do not survive through gestation. BCOR can mediate transcriptional repression by the oncoprotein BCL6 and has the ability to reduce transcriptional activation by AF9, a known mixed-lineage leukemia (MLL) fusion partner. The essential role of BCOR in development and its ability to modulate activity of known oncogenic proteins prompted us to determine the expression profile of Bcor during mouse development. Identification of independently transcribed exons in the 5' untranslated region of Bcor suggests that three independent promoters control the expression of Bcor in mice. Although Bcor is widely expressed in adult mouse tissues, analysis of known spliced isoforms in the coding region of Bcor reveals differential isoform usage. Whole mount in situ hybridization of mouse embryos shows that Bcor is strongly expressed in the extraembryonic tissue during gastrulation and expression significantly increases throughout the embryo after embryonic turning. During organogenesis and fetal stages Bcor is differentially expressed in multiple tissue lineages, with a notable presence in the developing nervous system. Strikingly, we observed that Bcor expression in the eye, brain, neural tube, and branchial arches correlates with tissues affected in OFCD patients. PMID- 17344104 TI - Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS. AB - A robust and validated liquid-liquid extraction LC-MS/MS method was developed for population pharmacokinetic analysis and therapeutic drug monitoring of risperidone and the enantiomers of its major active metabolite (+)-and (-)9 hydroxyrisperidone in pediatric patients. The method was rapid, sensitive and used a low sample amount (200 microL), which is very desirable for the pediatric population. The assay was validated from 0.2 to 50 ng/mL in plasma for all analytes. LLOQ for all analytes was 0.2 ng/mL. The extracts were analyzed by normal phase LC-MS/MS. The sample run time was 8 min. Intra- and interday precision for all analytes was < or =6%; method accuracy was between 89 and 99%. Additional experiments were performed to analyze matrix effects and identify a proper internal standard for each analyte. The validated method was used to study risperidone and its enantiomer metabolites in plasma as part of a population pharmacokinetic study in pediatric patients with pervasive developmental disorder (PDD). PMID- 17344105 TI - Chromatographic and mass spectrometric methods for quantitative determination of 3-nitrotyrosine in biological samples and their application to human samples. AB - The permanent modification of soluble and protein-associated tyrosine by nitration results in the formation of 3-nitrotyrosine, which can be used as a marker of "nitro-oxidative" damage to proteins. Based on the analysis of patient materials, over 40 different diseases and/or conditions have been linked to increased nitration of tyrosine. They include many cardiovascular diseases, conditions associated with immunological reactions and neurological diseases. In this article we review the existing chromatographic and mass spectrometric methods for quantitative measurements of 3-nitrotyrosine in different human biological samples including plasma, either from the free amino acid pool or from hydrolyzed proteins from different matrices. PMID- 17344106 TI - Micro-thermal field-flow fractionation of bacteria. AB - The retention of Staphylococcus epidermidis bacteria cells, achieved with the use of micro-thermal field-flow fractionation and described in this paper, represents the first experimental proof that the separation and characterization of the bio macromolecules and biological particles is possible by exploiting Ludwig-Soret effect of thermal diffusion. The experiments were carried out under gentle experimental conditions preventing the denaturation of the bacteria. Lift forces, appearing at high linear velocities of the carrier liquid, generated the focusing mechanism of the retention which resulted in high-speed and high-performance separation performed in less than 10 min. PMID- 17344107 TI - Recent methodological advances in the analysis of nitrite in the human circulation: nitrite as a biochemical parameter of the L-arginine/NO pathway. AB - Nitric oxide (NO) plays a pivotal role in the modulation of multiple physiological processes. It acts as a messenger molecule within the cardiovascular system. NO is a highly unstable free radical in circulating blood and is oxidized rapidly to nitrite and nitrate. Recent studies suggest that nitrite has the potential to function as a surrogate of NO production under physiological and pathophysiological conditions and could therefore be of high relevance as a biochemical parameter in experimental and clinical studies. Under hypoxic conditions nitrite is reduced to bioactive NO by deoxyhemoglobin. This mechanism may represent a dynamic cycle of NO generation to adapt the demand and supply for the vascular system. Because of these potential biological functions the concentration of nitrite in blood is thought to be of particular importance. The determination of nitrite in biological matrices represents a considerable analytical challenge. Methodological problems often arise from pre-analytical sample preparation, sample contamination due to the ubiquity of nitrite, and from lack of selectivity and sensitivity. These analytical difficulties may be a plausible explanation for reported highly diverging concentrations of nitrite in the human circulation. The aim of this article is to review the methods of quantitative analysis of nitrite in the human circulation, notably in plasma and blood, and to discuss pre-analytical and analytical factors potentially affecting accurate quantification of nitrite in these human fluids. PMID- 17344108 TI - Developing primary and secondary services for drug and alcohol dependent mothers. AB - Since the 1980s there has been a gradual introduction of women-centred programmes to address the needs of women who use legal and illegal drugs. But questions related to pregnancy and birth in relation to maternal drug use have proved more difficult to address and, in the USA in particular, policy and practice remains quite punitive. This article explores contemporary moral concerns and the practices related to drugs, pregnancy and mothering. It considers how sociohistoric factors have contributed to the development, or not, of women centred harm-reduction services for pregnant women and their infants. British programmes are seen to offer public health and harm-reduction initiatives rather than just crime control. To demonstrate this, an overview of the role of a consultant midwife in providing comprehensive primary and secondary services for drug and alcohol dependent mothers in Manchester, UK is given and compared with Canadian programmes. Finally, the possible ways forward will also be explored. PMID- 17344109 TI - Effects of surgical holes in mouse tibiae on bone formation induced by knee loading. AB - Loads applied directly to the knee (knee loading) have recently been demonstrated to induce anabolic responses in femoral and tibial cortical bone. In order to examine the potential role of intramedullary pressure in generating those knee loading responses, we investigated the effects of drilling surgical holes that penetrated into the tibial medullary cavity and thereby modulated pressure alteration. Thirty-nine C57/BL/6 female mice in total were used with and without surgical holes, and the surgical holes were monitored with micro CT and histology. The left knee was loaded for 3 days, and the contralateral limb was treated as a sham-loaded control. Mice were sacrificed for bone histomorphometry 2 weeks after the last loading. Although the surgical hole induced bone formation in both loaded and non-loaded tibiae, due to regional and systemic acceleratory phenomenon the anabolic effect of knee loading was substantially diminished. Without the holes, knee loading significantly elevated cross-sectional cortical area, cortical thickness, mineralizing surface, mineral apposition rate, and bone formation rate on the periosteal surface. For example, the rate of bone formation was elevated 2.1 fold (p<0.001; middle diaphysis--50% site from the knee along the length of tibiae) and 2.7 fold (p<0.01; distal diaphysis--75% site). With the surgical holes, however, knee loading did not provide significant enhancement either at the 50% or 75% site in any of the histomorphometric measurements (p>0.05). The results support the idea that alteration of intramedullary pressure is necessary for knee loading to induce bone formation in the diaphysis. PMID- 17344111 TI - [Surgery of the mitral valve--in the work of Jozsef Kudasz]. AB - The author described his results of surgical treatment of mitral valve disease. Of 57 patients, the isolated mitral procedure was performed in 72%, and the combined (valve and coronary) in 28% of the cases. In 75% of the patients valve repair, and in 25% valve replacement were performed. There were 2 cases (3.5%) of early mortality after combined surgery where patients had also ischaemic heart disease. All the replaced valve prostheses and 84% of repaired mitral valve had a normal function. The mitral regurgitation was moderate in 14%, of cases and mild in 2% of cases at the follow up, but no reoperation was needed. After the surgery 85% of patients had sinus rhythm, 13% had atrial arrhythmia and in 2% the pacemaker was needed. Attempt of valve repair had to be made in all patients with mitral valve disease which can be performed in almost every case of degenerative valve prolapse and the rupture of chordae tendineae. PMID- 17344112 TI - [Hepatitis C viral infection and depression]. AB - About 170 million individuals can be found with chronic hepatitis C viral infection all over the world. The occurrence of depression is more frequent among the persons than in the healthy population, this depression can be found in 58 per cent of patients with chronic hepatitis C. On the basis of the literature the authors review the aetiology of depression in liver diseases, examining the neuropathogenic effect of HCV. They demonstrate the scientific results which are evidences of hepatitis C viral infection for the alterations in the central nerve system. The depression is one of the side effects of the alpha-interferon treatment used in the therapy of HCV. The authors demonstrate the biological basis, development, consequences of depression produced by interferon and they give a review of the protocol in the diagnostic procedure of a patient with depression. They summarize the steps of psychiatric drug therapy in chronic liver diseases. That is also important whether the chronic HCV infected patient with depression can be treated with interferon. The loss of interferon treatment can lead to the fatal outcome of liver disease. In order to have the correct decision a collaboration between internist and psychiatric specialist is necessary. PMID- 17344113 TI - [Glycaemic control and macrovascular complications in patients with diabetes mellitus]. AB - According to a recent meta-analysis, proper glycaemic control due to intensive antidiabetic treatment could result in a decrease of cardiovascular complications in patients with diabetes mellitus. In comparison to conventional treatment, the relative risk reduction proved to be higher in type 2 than in type 1 diabetic patients. Although a decrease in incidence rate of cardiovascular complications could be documented in different areas (coronary, carotid and peripheral arteries), the decrease was different in terms of numerical changes. Comparing intensive and conventional treatment, no difference in mortality rate could be observed. PMID- 17344114 TI - [Adulthood atopic dermatitis: epidemiology, clinical symptoms, provoking and prognostic factors]. AB - The prevalence of atopic diseases, including allergic rhinitis, asthma bronchiale and atopic dermatitis is increasing both in children and adults at different parts of the world. Atopic dermatitis is a chronic inflammatory skin disease affecting mostly children, but the atopic trait continues, not only for later respiratory allergies, but also for skin symptoms in adulthood. In this form dry skin, flexural lichenification, head and neck dermatitis, hand dermatitis are typical. The exact etiology of atopic dermatitis is unknown, in the background interactions of genetical predisposition, skin barrier defects and immunological and environmental factors can be verified. In the complex approach of atopic dermatitis, a pivotal role is ascribed to the evaluation and possibly the elimination of provoking factors, like gender, family structure, clothing, aero-, alimentary and contact allergens, psychosocial stress, migration, infections, and personal home environment. Authors review clinical manifestations, triggering and prognostic factors of the adulthood atopic dermatitis. PMID- 17344115 TI - [Features of publications of Hungarian medical universities as reflected in numbers]. AB - INTRODUCTION: The majority of scientific results from Hungarian Medical Universities are published in international periodicals in foreign languages. AIM: This study shows that in what numbers, with what kind of impact factors and where the results of the scientific work in the Hungarian Medical Universities are published. METHODS: The examined period is between 2000 and 2003. These scientific publications were explored by two methods based on the own assembled bibliographies of the Hungarian medical universities - University of Debrecen Medical and Health Science Center, University of Pecs Medical School, University of Semmelweis and University of Szeged Albert Szent-Gyorgyi Medical and Pharmaceutical Center - and the Web of Science's recording. RESULTS: The scientific publications from our medical universities are published in great number and generally with increasing impact factors to guarantee the international publicity for the Hungarian researches. The 90-95 percent of publications which are intended for international publicity is published in those international journals which have impact factor. Among these journals there are many prestigious ones. CONCLUSIONS: Neither of the two methods which were used for exploring of publishing activity has decisive validity. The institutional reason for this is the insufficiency and the lack of precision of the bibliographies of the universities. In the authors' opinion it would be necessary to develop a uniform, electronic processing and take it over in each universities. So a national scientific database of medical universities would be created by joining these universities' databases. PMID- 17344119 TI - [Injection sclerotherapy for varicosities of the lower limb: 25 years of experience with 115000 injections]. AB - INTRODUCTION: The author began to deal with injection sclerotherapy 25 years ago, which is still being practised by him to this day. PATIENTS: Experience is drawn from 115 000 injections given to 4025 limbs of 3107 patients. The mean age is 41.7 years, 80.3% of patients were women. METHOD: For decades, medicines necessary for sclerotherapy (polidocanol, tetradecylsulphate) have been available in Hungary. At the same time diagnosis and method have developed both abroad and in Hungary. Instead of the previously used standard standing position, the patient is either sitting or lying during the puncture. The diameter of the needle used is smaller than earlier. Previously at the injection the patient was lying and her leg was raised, but now usually she is in the same position as during the puncture. The amount of given medicine at one session was 1 x 0.2 ml, later 4 and 6 x 0.5 ml, but now the allowed maximal dosage is 28 ml 0.5%. RESULTS: Treatments were successful in every case and there were not any serious complications. This method has an outstanding importance in the treatment of intracutaneous venectases and reticular varicosis but side branches and perforators can be cured as well. As is well known, varicosity is a progressive disease and the sclerotherapy can be repeated unrestricted. It is therefore suitable for its treatment in the long run. Strong reactions and complications: The most common strong reactions are fainting, suffusion, phlebitis and pigmentation at the site of the injection. COMPLICATIONS: Very rarely blistering, allergic reaction and deep venous thrombosis. The latter is highly focused, therefore the patient's thrombophilic history is revealed. The authors' results and the survey in Hungary showed 1.5% complication in treated patients including one non serious deep venous thrombosis. The recently introduced ultrasound-guided foam sclerotherapy of the leg is suitable for the injection of stem varicosities. Successful treatments were carried out not only in the lower leg but also in upper limb varicosities, vascular malformations, venous lake of the lip and hemorrhoidal nodes. The sclerotherapy and operation rather supplement each other than compete. CONCLUSION: Sclerotherapy has proved to be suitable for the therapy of lower limb varicosity and some other venous dilatations. PMID- 17344120 TI - [Role of transoesophageal echocardiography in bacteremia caused by Staphylococcus aureus]. AB - Treatment and prognosis of bacteremias caused by Staphylococcus aureus is different, whether only bacteremia is present or it is complicated with endocarditis. Transoesophageal echocardiography may have a role in evaluation of bacteremias caused by Staphylococcus aureus to confirm or exclude infective endocarditis. The aim of this study was to characterize patients with infective endocarditis. PATIENTS AND METHOD: We reviewed the patients studied with transoesophageal echocardiography at our institute between October 1988 and March 2002. The reason for transoesophageal echocardiography was bacteremia caused by Staphylococcus aureus. A total of 24 patients data were analyzed, 15 male and 9 female. Suspicion of infective endocarditis was in 11 patients with native valves, in 8 patients early after prosthetic valve implantation, in 2 patients late after prosthetic valve implantation and in 3 patients after pacemaker implantation. Patient's data were analyzed retrospectively. RESULTS: Thirteen patients had infective endocarditis and 7 of them had community acquired infection. Native valve, prosthetic valve and left ventricular thrombus were the infected tissues. Vegetation was present in 11 patients, one of them was infection of the left ventricular thrombus. Paravalvular leak was found in 3 patients and abscess in 2. Three out of 7 patients with native valve infective endocarditis presented on a structurally normal valve. Eleven patients had no infective endocarditis, in 9 of them there was nosocomial bacteremia. Surgery was performed in 8 patients with infective endocarditis: 3 with acute, 3 with subacute and 2 with late infection. Two patients died after surgery, one of them had acute infection. Four medically treated patients were cured and one died. From the 11 patients without infective endocarditis 7 were cured and 4 died. At the autopsy infective endocarditis was diagnosed in one out of 4 patients. Transoesophageal echocardiography was performed in this patient 4 weeks before death. CONCLUSION: The authors' date suggest, that transoesophageal echocardiography is the diagnostic tool for differentiation between bacteremia and infective endocarditis. The infective endocarditis in both community acquired and nosocomial Staphylococcus aureus bacteremia can cause infective endocarditis on native valves, in thrombus and on intracardiac materials. PMID- 17344122 TI - [The health care system as a new factor of competitiveness and the convergence program]. AB - The new governmental and convergence programs have given a new impulse to the transformation of the health care system in Hungary. It is important how are the financial conditions of the ambulatory and hospital treatment assuring the medical attendance of the Hungarian population. The paper defines the health care system as a new factor of the national competitiveness, the functioning of which is widely affected by the fiscal-financial situation related to the new convergence program. The study demonstrates with empirical methods that the health care and the social security system can also face problems and difficulties if the budget deficit persists. The planned rationalisation measures in the health care system make difficult the reintegration of the socially marginalized people who do not participate to the division of labour. Due to the financial problems of the health care system, the medical prevention and the stable participation of the active labour force in the division of labour can not be assured, so the health care system as a new factor of competitiveness has to be developed. In the coming years it is reasonable to calculate with increasing tasks in the health care system, which does not mean more austerity, but more resources, since the health care system creates value and so it represents a new type of competitiveness. PMID- 17344121 TI - [Effect of healthy life style in overweight and obese patients]. AB - Obesity is an important risk factor for cardiovascular diseases. Change of life style plays very important role for the management of overweight and obesity and related cardiovascular risk factors. Patients need to acquire and adopt these changes. The aim of this study was to screen practices for overweight and obese patients, to decrease their cardiovascular risk and prevent development of cardiovascular diseases. 2489 overweight patients were screened from 29 general practices since April of 2001. The authors surveyed their characteristics of life style: eating and exercise habits, body mass index, waist line, resting blood pressure, heart rate and plasma glucose, total cholesterin, triglyceride, HDL after a 12-hour fasting. A team, which consisted of an internist, a dietician and a physical instructor dealt with the patients. After ruling out secondary obesity the team tailored an individual life-style which focused on dietary interventions (low calorie diet) and increased physical activity. 12 months later the body mass index decreased significantly by 0.56 kg/m 2 on average and further 0.088 kg/m 2 by the end of the second year, the waist line first did not change significantly then decreased 0.04 cm. The rest systolic blood pressure cut down significantly on average 5.9 Hg mm in the first year, and more 0.11 Hg mm by the end of second year. The metabolic parameters also decreased significantly: total cholesterin 0.23 mmol/l in the first year, 0.07 mmol/l in the second year, triglyceride: 0.18 mmol/l; 0.08 mmol/l, blood glucose: 0.15 mmol/l; 0.19 mmol/l. The level of HDL did not change. It is very important for management of overweight and obesity that patients adopt changes of life style. The authors' results show that these patients must be followed very strictly. PMID- 17344123 TI - [Unusual case of orthostatic tachycardia]. AB - Orthostatic intolerance and postural tachycardia are common complaints, often caused by hypovolemia, antihypertensive medications, diuretics or alcohol. These symptoms could also be related to autonomic failure. Although upright posture renders patients more susceptible to provocation of supraventricular tachyarrhythmias in the electrophysiologic laboratory, orthostasis by itself seldom enough for the induction of such arrhythmias. The authors hereby present a patient, whose AV nodal reentry tachycardia could be provoked by head-upright tilting. Vagal maneuvers could terminate the tachycardia by decreasing the conduction in the slow anterograde pathway, however these maneuvers were successful only after assuming supine posture. The authors' report illustrates the role of autonomic influences, and the mechanism of vagal maneuvers in terminating this common arrhythmia. PMID- 17344124 TI - [Hungarian Medical Journal hundred years ago]. PMID- 17344126 TI - [Re: Changes in the perinatal management of congenital diaphragmatic hernia in the last 15 years' experience of our institute]. PMID- 17344128 TI - [Genetic background of multifactorial liver and bile duct diseases]. AB - The majority of liver diseases, are complex. They are the results of interactions between several genes and environmental factors. Familial aggregation and higher concordance rate of monozygotic twins compared to those of dizygotic twins provide evidence for the importance of genetic factors in the pathogenesis. There are only limited data in connection with the genetic background of multifactorial liver diseases. In the future, the genetic background may permit prevention, early, accurate diagnosis, prediction of disease course, complications, prognosis, as well as treatment response. PMID- 17344129 TI - [Applicability of the abbreviated version of the World Health Organization's quality of life questionnaire in Hungary]. AB - INTRODUCTION: Quality of life, as a subjective parameter of the general condition, is suitable for characterization of the health status of populations or patient groups, and for studying the effects of therapeutic or preventive interventions. AIMS: To test the applicability and reliability in Hungary of the abbreviated form of the quality of life questionnaire developed by WHO, one of several ways to measure the quality of life. METHODS: Questionnaire-based cross sectional investigation was performed among altogether 814 persons, in small settlements of population under 1000 and 2000, and in a small town for control, in Csongrad county, Hungary. The reliability and validity of the quality of life questionnaire was tested, within each group of questions, by means of Cronbach's alpha, ANOVA and Kruskal-Wallis tests, and by Spearman's rho correlation coefficient. RESULTS: The mean values of the four domains of quality of life - physical, psychological, social and environmental - showed no noteworthy differences. The Cronbach's alpha figures of the internal consistency test on separate groups of questions and on all questions were in all cases above the expected minimum of 0.7. The means calculated for each domain of quality of life were decreasing with increasing age. Healthy people estimated each aspect of quality of life as significantly better, compared to the sick. Correlation tests showed that all dimensions of the quality of life were in close positive correlation with the general quality of life, with the level of satisfaction with the own health, with the self-assessed health, and with the responses given on other questions related to the social or health situation of the questioned. CONCLUSION: The variation of the questionnaire, adapted to Hungarian conditions, proved to be suitable for testing the quality of life of persons with various demographical, social and health conditions, and for distinction between the healthy and the sick. The sheet, which can be filled in quickly and easily, enables the measurement of quality of life in the Hungarian population, and the comparison of that with international data. PMID- 17344130 TI - [Transgastric gastro-jejunal anastomosis with flexible endoscope on a biosynthetic model]. AB - INTRODUCTION: In the last few years the rapid development of flexible endoscopies has opened new possibilities in minimal invasive procedures. With the help of these techniques the exposure, the risk of complications and the healing period of the patient might be reduced. One of these procedures is the transgastric intervention. Through an incision on the wall of the stomach, the endoscope could be led into the abdominal cavity, where several interventions can be performed. The aim of the study was to examine the technical feasibility and the success of the formation of gastro-jejunal anastomosis. Meanwhile the difficulties of the method could be explored in order to introduce this method in human use. METHOD: A lifelike biosynthetic model was made from a slaughtered domestic pig's gastrointestinal tract (stomach and the first few jejunum loops) which was fixed onto a plastic frame. Two single-channel gastroscopes were inserted into the stomach. On the wall of the stomach an approximately 2 centimetres wide incision was made by the electrocoagulator with a needle-knife. Through it the first jejunum loop was grasped by a foreign-body forceps and then was retracted into the stomach. Subsequently the jejunum loop was held safely with the first endoscope. Parallel to it an incision was made on the jejunum by the electrocoagulator. The authors managed to securely unite the open edges of the gastric wall and the jejunum with endoclips. RESULT: The model was good for practising. The anastomosis is technically feasible and was successfully made on biosynthetic porcine model using the transgastric route. Although the incisions both on the gastric wall and on the jejunum loop were made easily, the fixing of the anastomosis might be questionable. CONCLUSION: It was revealed that more experiments and the development of new, special instruments are needed in order to conduct the anastomosis safely. PMID- 17344131 TI - [The unknown acquaintance, or the impact factor and others]. AB - Nobody doubts the importance of the scientific performance's evaluation. At the same time its way divides the group of experts. The present study mostly deals with the models of citation-analysis based evaluation. The aim of the authors is to present the background of the best known tool - Impact factor - since, according to the authors' experience, to the many people use without knowing it well. In addition to the "non-official impact factor" and Euro-factor, the most promising index-number, h-index is presented. Finally new initiation - Index Copernicus Master List - is delineated, which is suitable to rank journals. Studying different indexes the authors make a proposal and complete the method of long standing for the evaluation of scientific performance. PMID- 17344132 TI - [Recommendation of the Health Sciences Council's Presidency regarding the legal prerequisites for the legal use of AVEMAR dietary supplement as a neoplastic agent]. PMID- 17344133 TI - [In memoriam: Kalman Rak (1929-2005) - Imre Hirschler (1906-1989)]. PMID- 17344134 TI - [Bacteriology--in memory of it's most avid master, Jozsef Fodor]. PMID- 17344136 TI - [Celiac disease relatively frequently associated with sex chromosome aberrations]. PMID- 17344137 TI - [Champix has become a registered drug]. PMID- 17344138 TI - [24th Congress of the International Association of Hepatic Research]. PMID- 17344139 TI - [Treatment of iatrogenic Cushing syndrome: questions of glucocorticoid withdrawal]. AB - Iatrogenic Cushing's syndrome is the most common form of hypercortisolism. Glucocorticoids are widely used for the treatment of various diseases, often in high doses that may lead to the development of severe hypercortisolism. Iatrogenic hypercortisolism is unique, as the application of exogenous glucocorticoids leads to the simultaneous presence of symptoms specific for hypercortisolism and the suppression of the endogenous hypothalamic-pituitary adrenal axis. The principal question of its therapy is related to the problem of glucocorticoid withdrawal. There is considerable interindividual variability in the suppression and recovery of the hypothalamic-pituitary-adrenal axis, therefore, glucocorticoid withdrawal and substitution can only be conducted in a stepwise manner with careful clinical follow-up and regular laboratory examinations regarding endogenous hypothalamic-pituitary-adrenal axis activity. Three major complications which can be associated with glucocorticoid withdrawal are: i. reactivation of the underlying disease, ii. secondary adrenal insufficiency, iii. steroid withdrawal syndrome. Here, the authors summarize the most important aspects of this area based on their clinical experience and the available literature data. PMID- 17344140 TI - [Role of the activating mutation Val617Phe of Janus kinase 2 gene in myeloproliferative diseases and significance of its detection]. AB - The Val617Phe point mutation of Janus kinase 2 gene is believed to participate in the pathogenesis of myeloproliferative syndrome characterised by the clonal alteration of hematopoietic stem cells. According to current results, the frequency of Val617Phe activating mutation is around 80% in polycythaemia vera, 35% in essential thrombocythemia, and 50% in chronic idiopathic myelofibrosis. The diagnoses of polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis were so far based on the exclusion of secondary factors as well as bone marrow biopsy histology. The goal of the present work was to establish simple molecular genetic techniques for the routine testing of Janus kinase 2 gene Val617Phe mutation, and to compare the clinical phenotypes of Val617Phe mutation positive and negative myeloproliferative syndromes. We employed the allele specific polymerase chain technique for detection of Val617Phe mutation in 252 patients with myeloproliferative syndrome. We measured Val617Phe frequency as 85,4% (117/137) in polycythemia vera, 56,6% (56/99) in essential thrombocythemia, and 87,5% (14/16) in idiopathic myelofibrosis. We found significantly elevated hemoglobin levels and white blood cell counts (measured at the time of diagnosis) in Val617Phe-positive polycythemia vera and essential thrombocythemia patient groups compared to Val617Phe-negative patients. However, the frequencies of splenomegaly and other complications (thrombosis, bleeding, transformation to acute leukemia) were not significantly different between the mutation-positive and negative groups. In conclusion, the non-invasive mutation analysis of the Janus kinase 2 Val617Phe is suitable for routine laboratory application and helps the differential diagnosis of myeloproliferative syndrome. Although the exact role of Val617Phe mutation testing has not yet been identified on the basis of a broad professional consensus, the testing is suggested in cases of erythrocytoses and thrombocytoses of unknown origin. PMID- 17344141 TI - [Increase in prevalence of childhood asthma in Budapest between 1995 and 2003: correlation with air pollution data and total pollen count]. AB - INTRODUCTION: According to the data of the Hungarian pulmonological network, the prevalence of asthma in the last 15 years has increased (almost linearly) in Hungary. In 2004 it was 1.8%. There are only a few data about the prevalence of childhood asthma. AIMS: The aim of the authors was to measure the prevalence of bronchial asthma in childhood in Budapest in 1995, 1999 and 2003, using questionnaires directed to district pediatricians. METHODS: There were only two questions in these questionnaires: how many children are in their districts, and how many are suffering from asthma? Besides of this survey the dust, CO, NO(2) and SO(2) concentrations in the air were measured on-line at 8 points in Budapest, while ozone level measurements were also made at 2 stations. The counts of pollen and of fungal elements in the air were calculated separately for Buda and for Pest. RESULTS: In 1995, replies were received from 118 pediatricians in 11 districts, who were responsible for the supervision of 104,060 children, out of these 1.88+/-0.87% had been diagnosed as having asthma. In 1999 replies were sent by 153 physicians in 22 of the 23 districts, who had a total of 142,679 children under their care. These included 3228 asthmatics, i.e. a prevalence of 2.26+/-0.95%. In 2003 the authors received answers from all of the 23 districts of Budapest. The 204 pediatricians were responsible for the supervision of 176 049 children. The number of patients with the diagnosis of asthma was 4712 (corresponding for a prevalence of 2.68+/-1.3%). The increase between 1995 and 1999, and between 1999 and 2003 was highly significant (p < 0.0001). This significant increase was valid even when the authors analysed only those 11 districts, which answered already in 1995. The level of air pollution in Budapest did not deteriorate in the period in question, and the concentration of pollen grains of plants causing allergy did not increase compared to previous years. CONCLUSIONS: On the basis of the results of more than 100 thousand children, the authors conclude that between 1995 and 2003 the proportion of asthmatic children increased by 50% in Budapest, while the air pollution did not deteriorate and the pollen concentration from sensitizing plants did not increase. PMID- 17344142 TI - [B-type natriuretic hormone--diagnostic and prognostic cardiovascular biomarker]. AB - Brain natriuretic hormone and N-terminal-probrain natriuretic hormone are equally important cardiovascular biomarkers. Moderately increased brain natriuretic hormone level is a reliable predictor of preclinical, asymptomatic left ventricular dysfunction. Low brain natriuretic hormone levels are extensively used to rule out acute heart failure. Increased brain natriuretic hormone is associated to age, left ventricular hypertrophy, left atrial volume, atrial fibrillation, myocardial ischemia, renal failure, pulmonary hypertension, acute pulmonary embolism and progressive aortic stenosis. In chronic heart failure only high brain natriuretic hormone values support the diagnosis. High brain natriuretic hormone level, however, is an important overall cardiovascular prognostic biomarker. In the near future brain natriuretic hormone appears to be an interesting new therapeutic modality. PMID- 17344143 TI - [Changes in the epidemiology of inflammatory bowel diseases]. AB - Significant changes have been observed in the epidemiology of inflammatory bowel diseases (IBD) in the last two decades. Traditionally, the incidence of IBD was higher in the developed, industrialized countries, in contrast, nowadays it became more prevalent in the previously low incidence areas. In particular, the incidence of ulcerative colitis (UC) is similar to that observed in North America and Western Europe, while the incidence of Crohn's disease (CD) in developing countries is still low, suggesting that the environmental factors may act faster or differently in UC than in CD. In Europe, the North to South gradient disappeared, and also the West to East gradient is diminishing. Smoking and appendectomy may be considered as important environmental factors in both UC and CD, however, with opposite effects. In addition, the use of oral contraceptives is associated to disease susceptibility in both diseases. The role of diet, perinatal events, stress and nonsteroidal anti-inflammatory drugs in the pathogenesis is still controversial. PMID- 17344144 TI - [Hospital-acquired pneumonia]. PMID- 17344148 TI - [Medicating outside the consulting room]. AB - INTRODUCTION: Self-medication is a means, besides changing one's lifestyle, of buying and taking non-prescription medicaments. This practice has several advantages. People save time and energy by not sitting for hours in the consulting room of the doctor with a simple ailment, and the doctors also have more time to deal with those requiring more serious treatment. Moreover, the expenditures of the state also decrease, as patients do not visit the doctor but buy non-prescription, i.e. non-supported, medicaments. AIMS: The authors surveyed the habits and demands of a survey population concerning non-prescription medicaments, primarily in the pharmacies of Fejer county. A marketing research programme was completed in order to establish better co-operation between patients and pharmacists, within the framework of which 1450 questionnaires were distributed from March to June in 2005, 743 of which were completed and evaluated. METHOD: The authors examined, whether there were differences within the answers given to professional questions (questions 1-25 of the questionnaire) through sex, age, qualifications and earning power. Answers were analyzed by statistical methods. Statistical analyses were carried out with the SPSS 13.0 program group. Those results were published, where significant differences were found. RESULTS: Half of the respondents take medicaments regularly, 65% of them watch advertisements about medicaments several times a day. 40% of those surveyed consult a professionally-qualified person about their decision before buying non prescription medicaments. The population obtains much information from the brochures enclosed with medicaments, and almost 70% of them read these brochures. According to their opinions, when buying non-prescription products, pharmacists always recommend other possibilities as well, and they give details about the information concerning the application of the medicaments. CONCLUSIONS: In order for people to use non-prescription products properly, it would be definitely necessary to elaborate a successful national education strategy. The population expects information concerning medicaments to be communicated in the pharmacies in an understandable way. It should be in the pharmacy where patients learn about the medicaments they take, where the pharmacist knows what other medicines have been prescribed by a doctor, and whether patients have any illnesses whereby they should not take other products. PMID- 17344149 TI - [The laboratory diagnosis of food allergies]. AB - This paper summarizes the most common allergens in Hungary, the various forms of food allergies, the tools of their diagnosis, with special respect to the possibilities of in vitro laboratory tests. These thoughts are in accordance with the position papers of European Academy of Allergology and Clinical Immunology and Hungarian College of Clinical Immunology and Allergology. PMID- 17344150 TI - [Some neurologic and psychiatric complications in endocrine disorders: the thyroid gland]. AB - Thyroid hormones are of primary importance for the perinatal development of the central nervous system, and for normal function of the adult brain. These hormones primarily regulate the transcription of specific target genes. They increase the cortical serotonergic neurotransmission, and play an important role in regulating central noradrenergic and GABA function. Thyroid deficiency during the perinatal period results in mental retardation. Hypothyroidism of the adults causes most frequently dementia and depression. Other less common clinical pictures include myxoedema coma, dysfunction of cerebellum and cranial nerves. Hypothyroidism also increases predisposition of stroke. Peripheral diseases frequently include polyneuropathy, carpal tunnel syndrome, myalgic state, and rarely myokymia. Nearly all the hyperthyroid patients show minor psychiatric signs, and infrequently psychosis, dementia, confusion state, depression, apathetic thyrotoxicosis, thyrotoxic crisis, seizures, pyramidal signs, or chorea occur. The peripheral complications may be indicated by chronic thyrotoxic myopathy, infiltrative ophthalmopathy, myasthenia gravis, periodic hypokalemic paralysis and polyneuropathy. Generalized resistance to thyroid hormone was confirmed in a number of patients with attention deficit-hyperactivity disorder. Significantly elevated antithyroid antibody titers characterize Hashimoto's encephalopathy. This condition is a rare, acute - subacute, serious, life threatening, but steroid-responsive, relapsing-remitting, autoimmune disease. PMID- 17344151 TI - [Secondary IgA-nephropathy in gastroenterological diseases]. AB - IgA-nephropathy is the most common primary chronic glomerulonephritis worldwide. Beside the primary IgA-nephropathy (IgA-nephropathy with an unknown origin), there are more and more cases, which are associated with diseases of other organs. Although the causality is often not obvious, these forms are called secondary IgA-nephropathy. In this study, the authors cover only the secondary forms of IgA-nephropathy with relation to gastroenterology in a broader sense that includes the liver. They would like to draw the attention to the necessity of analyzing also the associate occurrence of gastrointestinal diseases (principally liver diseases, coeliac disease, Crohn's disease, ulcerative colitis) in patients with IgA-nephropathy, as well. They think that it would be expedient to organize a nationwide clinical analysis that would search the frequency of occurrence of IgA-nephropathy in the above mentioned gastrointestinal diseases. PMID- 17344152 TI - [Vitamin D forming effectiveness of ultraviolet radiation from sunlight in different months in Budapest, Hungary]. AB - INTRODUCTION: The vitamin D3 formation in skin is the most important natural source of vitamin D demands of humans. The key step of the phototransformation of provitamin D into previtamin D from which the vitamin D3 is formed by thermal conversion. According to studies run at the latitudes of Hungary the UV-B radiation in winter time is not satisfactory to ensure the need of the vitamin D, which can result in vitamin D 3 deficiency and increases risk of osteoporosis. AIMS: The aim of this study was to verify whether in the Hungarian population the UV radiation from the Sun ensures the daily synthesis of 1000 IU vitamin D3, or Vitamin D deficiency could occur in the winter and spring months which are less favourable in terms of UV exposure. METHODS: The data of UV-B radiation reaching the Earth's surface were used for the evaluation. These data based on regular measurements in Budapest. According to the average of UV-B radiation of each months the "best case scenario" of vitamin D3 production was estimated by using the most optimal conditions of vitamin D synthesis. RESULTS: It was calculated, that the effective UV irradiance reaching the Earth's surface at noon in Budapest is the highest in July, while the lowest is in December. The difference between these two months is more than 35-fold for July. In the period between November and March more than 200 minutes have to be spent outdoor to ensure the production of satisfactory amount of vitamin D in skin. On one hand, it is irrealistically long time because it exceeds the duration of maximum irradiation around noon which was the basis of our calculation. On the other hand, if only the face and hands are uncovered then the required radiant exposure exceeds the 1 minimal erythemal dose, i.e. the skin would be burnt. CONCLUSIONS: Based on our calculations it was found, that in Budapest more than 95% of yearly effective UV B radiation is measurable in the period between March and October. Therefore it can be assumed that the UV-B radiation would not be sufficient in the period between November and February, even if its efficacy would not be limited by clothing and less time spent outdoor which are anyway characteristic and necessary in that part of the year. PMID- 17344156 TI - [Micro-epidemic due to a new Mycobacterium tuberculosis strain among the homeless in Budapest, Hungary]. AB - In a retrospective study that included 66 homeless tuberculosis patients a local micro-epidemic was identified in the VIIIth district of Budapest with the highest tuberculosis incidence of the capital. Further molecular genetic characterization by IS 6110 fingerprinting, spoligotyping and mycobacterial inter-spread repetitive unit (MIRU) typing has shown that the observed micro-epidemic was due to a locally emerged, Budapest-specific lineage. The absence of infections with the more virulent Beijing genotype is also noteworthy. The findings indicate that tuberculosis control and prevention steps among the homeless need to be strengthened in Hungary. PMID- 17344157 TI - [Valsalva maneuver, Muller maneuver: hemodynamic and reflex mechanisms, relevance]. AB - The time honored ancient reflex tests, the Valsalva and Muller maneuvers are still popular in the everyday clinical practice. These maneuvers are capable of imitating both trivial situations and significant pathological conditions. The Valsalva maneuver is still frequently used for the assessment of autonomic neuropathy. Addition of continuous noninvasive blood pressure monitoring allows assessment of both cardiac vagal and sympathetic driven peripheral vasomotor responses. The Muller maneuver has recently gained renewed popularity in simulating episodes of obstructive sleep apnea (OSA). Continuous monitoring of arterial pressure and muscle sympathetic nerve activity (MSNA) casts light on the close relationship between OSA and circulatory abnormalities. PMID- 17344158 TI - [Dynamic tissue organizational view of the formation of functional immune system and medical perspectives of its research]. AB - Advances in molecular biological procedures, bioinformatics and transgenic technology and their rapidly broadening use have led to an immense increase of data concerning the cells comprising the immune system at molecular level. This new knowledge is mostly relevant to the hemopoietic components of structured lymphoid tissues, while similar research efforts aimed at investigating the non hemopoietic stromal parts have until recently been rather neglected. However, the results of recent investigations have established the importance of tissue differentiation and functional maturation of these latter components within the lymphoid organs during the embryonic development for achieving the individual's immunological competence, as manifested in various forms of immune responses. Research performed on murine embryos have revealed the origin and developmental pathways of these less investigated stromal components, identified the molecular participants involved in their interactions with lymphoid cells, and determined the anatomic location of lymphoid-stromal domains and the sequence of interactions between the two tissue partners. In addition to the obvious theoretical importance of the above events, their resemblance to the occurrence of certain pathological conditions with inflammatory origin has also become apparent, where the course of the disease is characterized by the formation of "tertiary lymphoid tissue" in the affected organ. A more detailed understanding of the dependence of hemopoietic cells on their stromal environment in the lymphoid tissues may offer support for establishing a more efficient causal therapy for chronic inflammations. The purpose of the present account is to report these developmental events, and to emphasize the importance of the stromal development and functional dynamics during the interpretation of immune functions and place them at least as important a diagnostic and therapeutic target as the current clinical evaluation hitherto mainly focussed on lymphoid cells. Familiarity with this aspect of lymphoid tissue formation through the appreciation of the roles played by stromal mesenchyma may also arouse interest for exploring more efficient treatment modalities for diseases with relevant immunopathogenesis. PMID- 17344159 TI - [Comparing the young asthmatics running fitness]. AB - INTRODUCTION: Nowadays, doctors strongly recommend physical activity for asthmatic children, since the resulting improved physical fitness and psychological change also raise the quality of life. AIMS: The aim of this study was to compare the physical fitness of asthmatic children who regularly participate in therapeutic swimming, with asthmatic children who do not participate in this training and with non-swimming, healthy children using the 12 minute free running, Cooper test. METHOD: The children from the swimmer asthmatic group (n= 51, age = 9-22 yrs) took part in a special, long term, swimming exercise program (Gyene method). Whereas, the non-swimmer asthmatics (n = 28, age = 8-22 yrs) and the healthy children (n: 179, age: 9-22 yrs) only took part in the normal school physical education classes. Fitness was measured using the Cooper test. RESULTS: Data was collected from 258 subjects and showed that the fitness of swimmer asthmatics is significantly better than that of the non swimmer asthmatics and even better than that of the healthy subjects (swimmer/ non swimmer asthmatic p = 0.01; swimmer asthmatic/ healthy p < 0.0001 Chi(2) test). The difference in the fitness acquired from swimming was the most pronounced for the 8-11 years old asthmatics, presumably because of greater motivational factors. No differences were found between genders for the two asthmatic groups, whereas healthy boys were found to have significantly greater levels of fitness than healthy girls. CONCLUSIONS: Fitness is substantially increased with regular swimming. The favourable effects of swimming are expressed not only in comparison with the non-swimmer asthmatics but with the healthy subjects too. The regular therapeutic swimming program helps the formation of running fitness too. PMID- 17344160 TI - [A simple surgical method for removing a large floating thrombus from the ascending aorta]. AB - We report the successful surgical removal of a large floating thrombus from the ascending aorta causing systemic embolization. It was diagnosed by transesophageal echocardiography (TEE), CT scan, aortography and Cardiovascular Magnetic Resonance Imaging (CMR). The free-floating, highly embolic source 2 cm distal to the left coronary sinus was removed from the ascending aorta using a simple surgical technique. Isolated cerebral perfusion with circulatory arrest on normothermia provided a simple and safe access to the thrombus attached to a ruptured atherosclerotic plaque. The patient was discharged on the 7 th postoperative day after an uneventful recovery. PMID- 17344161 TI - [Autoimmune hepatitis]. PMID- 17344162 TI - [Gynecology and pediatrics (1864-1865)--supplement of the (Hungarian) Medical Journal]. PMID- 17344163 TI - ["Public Health and Legal Medicine" (1865-1897)--an important supplement to the (Hungarian) Medical Journal]. PMID- 17344166 TI - [Bacterial infections in liver cirrhosis]. AB - Bacterial infections are well described complications of cirrhosis that greatly increase mortality rates. Two factors play important roles in the development of bacterial infections in these patients: the severity of liver disease and gastrointestinal haemorrhage. The most common infections are spontaneous bacterial peritonitis, urinary tract infections, pneumonia and sepsis. Gram negative and gram-positive bacteria are equal causative organisms. For primary prophylaxis, short-term antibiotic treatment (oral norfloxacin or ciprofloxacin) is indicated in cirrhotic patients (with or without ascites) admitted with gastrointestinal haemorrhage (variceal or non-variceal). Administration of norfloxacin is advisable for hospitalized patients with low ascitic protein even without gastrointestinal haemorrhage. The first choice in empirical treatment of spontaneous bacterial peritonitis is the iv. III. generation cephalosporin; which can be switched for a targeted antibiotic regime based on the result of the culture. The duration of therapy is 5-8 days. Amoxicillin/clavulanic acid and fluoroquinolones--patients not on prior quinolone prophylaxis--were shown to be as effective and safe as cefotaxime. In patients with evidence of improvement, iv. antibiotics can be switched safely to oral antibiotics after 2 days. In case of renal dysfunction, iv albumin should also be administered. Long-term antibiotic prophylaxis is recommended in patients who have recovered from an episode of spontaneous bacterial peritonitis (secondary prevention). For "selective intestinal decontamination", poorly absorbed oral norfloxacin is the preferred schedule. Oral ciprofloxacin or levofloxacin (added gram positive spectrum) all the more are reasonable alternatives. Trimethoprim/sulfamethoxazole is only for patients who are intolerant to quinolones. Prophylaxis is indefinite until disappearance of ascites, transplant or death. Long-term prophylaxis is currently not recommended for patients without previous spontaneous bacterial peritonitis episode, not even when refractory ascites or low ascites protein content is present. PMID- 17344167 TI - [Pathogenesis and treatment of pain in chronic pancreatitis]. AB - Chronic pancreatitis is an inflammatory, usually painful disease characterized by progressive fibrosis and the loss of exocrine and endocrine functions. Pain influences the quality of life of patients and may lead to inability to work and frequent hospitalisation. The pathogenesis of pain in chronic pancreatitis is still unclear. Several different mechanisms of pain have been proposed, but pain in chronic pancreatitis is most probably multifactorial. Pain management in chronic pancreatitis is difficult. This is due to the multifactorial origin, there are no standardized methods to quantify pain and patients are often addicted to alcohol in chronic pancreatitis. This review summarises the different hypotheses of pain and the possibilities of pain management in chronic pancreatitis. PMID- 17344168 TI - [Medical complications of anorexia nervosa in children and adolescents]. AB - Anorexia nervosa in children and adolescents is still a serious cause of morbidity and mortality which may result in premature death or life-long medical and psychosocial morbidity. This condition can cause significant medical complications in every organ system of the growing and developing body. Although many of these medical complications improve with nutritional rehabilitation and recovery from the disorder some are potentially irreversible. This article summarizes the evidence based literature on medical complications that has been specially studied in child and adolescent population with anorexia nervosa over the past two decades. This review of the literature focuses on the acute symptoms of anorexia nervosa with special emphasis on the fluid and electrolyte levels and refeeding syndrome, and details the cardiovascular complications. Summarizes the special alterations in childhood and adolescent anorexia nervosa such as impaired bone mineral accretion and the possible therapeutic interventions of osteopenia and alterations in linear growth. The reviewed literature suggests that the medical complications in adolescents with anorexia nervosa are different from those reported in the adult population. The unique clinical presentation, the early onset and the unknown impact of these complications underline the need for early identification and early efficient treatment of anorexia nervosa in adolescents. There is an increasing number of evidence that highlight the importance of interdisciplinary teams of healthcare providers in the identification and in the therapy of adolescent anorexia nervosa as well. PMID- 17344169 TI - [General symptoms of cornea Salzmann-type degeneration]. AB - After a brief review of the symptoms of Salzmann's nodular corneal dystrophy the authors report on 28 patients. As found by radiological examination, arthrosis deformans was present in all of the patients and, in nearly all cases, osteoporosis has been diagnosed. Histological examination revealed a regressive change in 3 patients' costal cartilage of identical macular character. 22 patients had cataracta and 20 an impaired hearing. Therefore, the disease belongs to the keratochondrosises. CONCLUSIONS: 1. The regressive change of the corneal stroma, the hyaline cartilage and the bones relies assumably on an abnormality of their mutual component, the mucopolysaccharides. 2. Experimental and therapeutic experiences have shown that prolonged mucopolysaccharide administration (heparin) will induce osteoporosis. This explains the relationship between osteoporosis and metabolic disorder of mucopolysaccharides. 3. The remarkably high occurrence of cataracta, in comparison to a normal population of the same age, is presumably related to the metabolic disorder of mucopolysaccharides. 4. The aforesaid seem to confirm that Salzmann's nodular corneal dystrophy, corneal dystrophy is not induced by repeated inflammations but conversely, pathological metabolism of the cornea in consequence of dystrophy is responsible for serial keratitis. PMID- 17344170 TI - [Acute renal failure caused by plant extract]. AB - The authors review the case of a 30 years old female patient presenting with a 48 hours-standing anuria, who permanently used products of grist of a virtuous plant, Guarana and occasionally used a parenteral non-steroid painkiller. The clinical history and laboratory results showed acute renal and hepatic failure. The histological picture of the renal biopsy specimen verified an acute tubular necrosis. After temporary dialysis treatment, her renal function recovered progressively with compensatory polyuria. The authors would like to draw the attention to the risks of the use of over-the-counter marketed paramedicinal products, per se or in combination with pharmaceutically registered products, sold in pharmacies and nutrition supplement stores. PMID- 17344171 TI - [Osteoporosis]. PMID- 17344174 TI - [Effects of autologous bone marrow derived CD34+ stem cells on the left ventricular function following myocardial infarction]. AB - Both experimental and human clinical studies executed in the last 5 years suggested that bone marrow derived cells may participate in the healing process after myocardial infarction. A number of small clinical trials indicated mild or moderate beneficial effect of intracoronary administration of bone marrow derived stem cells after myocardial infarction. Most of the studies used mononuclear cell fraction; due to the cellular heterogeneity of this cell population the type of the effective subpopulation was not known. We investigated the safety and functional effects of the autologous bone marrow CD34+ stem cells after intracoronary administration in patients with recent myocardial infarction. 8 patients with impaired left ventricular function were transplanted with CD34+ bone marrow stem cells 12 +/- 1 day after the acute coronary event. 2D echocardiography, FDG-PET and MIBI-SPECT were performed before transplantation and 6 month later. During the 6-month follow-up the global left ventricular function (basal EF 37.3 +/- 2.9%, after cell therapy 44.8 +/- 4.1%) and regional viability / metabolism increased significantly (17.6 +/- 13.5%). The increase of myocardial perfusion in the infarct region was tendentious but not significant. Our results demonstrate for the first time that the CD34+ subpopulation of bone marrow derived stem cells improves left ventricular function and viability after myocardial infarction. PMID- 17344175 TI - [The prompt effect of emedastine eye drop and the safety of its permanent use in children suffering from acute seasonal allergic conjunctivitis]. AB - INTRODUCTION: In the treatment of any disease, it is advantageous if the concentration of the administered drug is highest in the target organ. It follows that, if possible, diseases of the conjunctiva should primarily be treated with eye drops. AIMS: The author investigated the effect of an eye drop with selective H1-receptor antagonist properties, on children suffering from acute seasonal conjunctivitis. METHOD: During the first experiment 20 children (suffering from acute seasonal allergic conjunctivitis) had received Emadine eye drop (containing emedastine difumarate, an H1 antihistamine agent). The severity of the itching of the eye and the grade of hyperemia of the conjunctiva were scored on scales ranging 0 to 4 (score 4 representing the most severe symptoms). In the second experiment 232 other children had received this eye drop during two pollen seasons and the author investigated its effectiveness and side effects. RESULTS: The conjunctival itching decreased within less than 3 minutes significantly, and the redness was also reduced in an average of 8 minutes. In the second experiment none of the 232 children had to change this drug because of its ineffectiveness or side effects. CONCLUSIONS: Emadine eye drop decreases the itching and the redness of the conjunctiva very quickly and effectively. It is usable even for three-year-old patients, and it keeps its effectiveness during the long-term treatment, too. PMID- 17344176 TI - [Family study in Peutz-Jeghers syndrome]. AB - BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant hereditary disease characterized by mucocutaneous pigmentation, gastrointestinal hamartomatous polyposis and an increased risk for the development of gastrointestinal and extra-gastrointestinal malignancies. AIM AND METHODS: Five generations of two PJS families (21-21 patients) were analyzed to summarize the clinical appearance of the disorder by interview, physical examination, laboratory and imaging studies. RESULTS: Phenotypic variability was observed in PJS both in and between families. In family "A" 13 people were diagnosed as being affected, all of them had melanin spots at birth and the first presenting clinical symptom was colicky abdominal pain (median age 12 years, range: 2-35) resulting in 14 laparotomies in 9 of the affected persons. 4/13 patients died from small-bowel ileus (median age 7 years, range 2-31), 2/13 from GI cancer (median age 54 years). In family "B" 7 patients were documented as being affected. The first features were also abdominal cramps (at age 22). The main causes of death were gynaecological (1/5) and GI malignancies (4/5) at advanced age, no one died in ileus. CONCLUSIONS: The results based on the analysis of the two families suggest that PJS is not a benign disease. It is difficult to predict the outcome of the disorder regarding the variable expression and incomplete penetrance. Therefore we emphasize the importance of checking the pedigree, finding out the leading symptom in the family; hemoccult test and routine lab studies should be carried out at every affected individual. If clinical signs and symptoms are present we recommend to perform the complete diagnostic protocol and a yearly follow-up by a gastroenterologist familiar with PJS focusing on the leading symptoms. PMID- 17344177 TI - [Kinesiological examination in AIS]. AB - AIM: To define the shape of the scoliotic spine by the CMS-system, to analyze the changes of the scoliotic spine as compared to that of non-scoliotic patients and to study the effect of loading on the deformed spine in AIS. The aim of the authors was to find a connection between the progression of scoliosis and the changes of movements of the deformed spine. They also analyse the effect of loading on the deformed spine and reach conclusions with regard to the progression of the spine deformity. PATIENTS AND METHOD: In a prospective study 25 scoliotic patients with type King 1-2-3 scoliosis were examined. Mean Cobb grades were dorsal 27 degrees (min. 15, max. 42), lumbal 25 degrees (min. 14, max. 43). RESULTS: The significant increase of extension seems to be in connection with increased lordosis in scoliosis. The significant increase of right rotation in AIS emphasizes that very often the first sign is the increased rotation on the thoracic spine, which could be larger than the right curve on the spine itself. However, the significant decrease of left and right bending is not in correlation with the severity of the spine deformities. Up to 30 degrees Cobb grades the pp angle is in significant correlation with the Cobb grade, but over 30 Cobb grade this correlation is weak. CONCLUSION: During the clinical examination of the patient's spine only the "processus spinosus angle" may be observed, not the so-called Cobb angle, that is why we cannot leave out of consideration the X-ray analysis during the follow-up of the patients. The loading has a great influence on the degree of the gibbus and the severity of the thoracic curve. PMID- 17344178 TI - [Utility of B-type natriuretic peptide in children]. AB - Serum brain natriuretic peptide (BNP) has been reported to indicate ventricular dysfunction, however, in children it has not been studied yet in our country. PURPOSE: 157 BNP tests were performed in 107 children, on the one hand, to evaluate its clinical value, to assess LV or systemic RV function in patients with transposition of great arteries after Senning operation, on the other hand, to prove the relation between BNP, MRI and echocardiographic ventricular function parameters. PATIENTS' AGE: 4 months-20 years, mean 12.5 yrs. Group I: Senning patients, Groups II and III: patients with dilated or hypertrophic cardiomyopathy, Group IV: patients with aortic insufficiency. METHODS: BNP was determined using the electrochemiluminesce method (Elycsys-10 Roche). During the functional MRI Mass- Medis software RV LV EF, end-diastolic, end-systolic volumes were calculated. Echo M-mode, TEI index were calculated. RESULTS: BNPs were significantly as higher compared to normal in each group of patients. Group I: 318 +/- 285 pg/ml, p < 0.01, Group II: 7262 +/- 10970 pg/ml, p < 0.01, Group III: 1558 +/- 2765 pg/ml, p < 0.01, Group IV: 1076 +/- 2791 pg/ml, p < 0.00l, vs 58 +/ 31 pg/ml. BNP were negatively correlated with MRI RV EF (r: -0.51, p < 0.05) and showed good correlation with TEI index (0.43 +/- 0.18, p < 0.05). After 3 weeks of medical or surgical treatment BNP decreased significantly. 4 patients died during the follow-up period, these had the highest BNP levels in each patients group. CONCLUSIONS: BNP is a useful, prognostically valuable method in children to monitor ventricular function. BNP levels reflect the severity of the impairment of systemic RV function in Senning patients in whom a complex RV geometry is present causing the assessment of RV function more difficult, so we recommend BNP measurements as a longitudinal test in this patient group. PMID- 17344179 TI - [Brown's incitability study on the faculty of medicine in Pest--Samuel Racz and the Hungarian Brownists]. PMID- 17344181 TI - [International Society of Travel Medicine (ISTM), Northern-European Regional Conference, Edinburgh, June 7-10, 2006]. PMID- 17344183 TI - The nuclear import of the human T lymphotropic virus type I (HTLV-1) tax protein is carrier- and energy-independent. AB - HTLV-1 is the etiologic agent of the adult T cell leukemialymphoma (ATLL). The viral regulatory protein Tax plays a central role in leukemogenesis as a transcriptional transactivator of both viral and cellular gene expression, and this requires Tax activity in both the cytoplasm and the nucleus. In the present study, we have investigated the mechanisms involved in the nuclear localization of Tax. Employing a GFP fusion expression system and a range of Tax mutants, we could confirm that the N-terminal 60 amino acids, and specifically residues within the zinc finger motif in this region, are important for nuclear localization. Using an in vitro nuclear import assay, it could be demonstrated that the transportation of Tax to the nucleus required neither energy nor carrier proteins. Specific and direct binding between Tax and p62, a nucleoporin with which the importin beta family of proteins have been known to interact was also observed. The nuclear import activity of wild type Tax and its mutants and their binding affinity for p62 were also clearly correlated, suggesting that the entry of Tax into the nucleus involves a direct interaction with nucleoporins within the nuclear pore complex (NPC). The nuclear export of Tax was also shown to be carrier independent. It could be also demonstrated that Tax it self may have a carrier function and that the NF-kappaB subunit p65 could be imported into the nucleus by Tax. These studies suggest that Tax could alter the nucleocytoplasmic distribution of cellular proteins, and this could contribute to the deregulation of cellular processes observed in HTLV-1 infection. PMID- 17344184 TI - Losartan-hydrochlorothiazide association promotes lasting blood pressure normalization and completely arrests long-term renal injury in the 5/6 ablation model. AB - The possible long-term renoprotective effects of treatment with thiazides, either as monotherapy or associated with renin-angiotensin suppressors, have not been assessed. We investigated the effect of hydrochlorothiazide (H), alone or combined with losartan (L), in the 5/6 renal ablation model (Nx). Adult male Munich-Wistar rats underwent Nx, remaining untreated for 1 mo. At this time, functional and morphological studies were performed in 21 rats (group Nx(pre)). The remaining rats were distributed among groups: Nx, no treatment; Nx+L, receiving L, 50 mg kg(-1) day(-1) in the drinking water; Nx+H, receiving H, 6 mg kg(-1) day(-1) in drinking water; and Nx+L+H, receiving both L and H as described. At 30 days of treatment, systemic and glomerular pressures were markedly elevated in group Nx. Both H and L attenuated hypertension, whereas combined L+H treatment completely normalized both pressures. Eight months after Nx, mortality approached 70% in untreated rats, whereas severe albuminuria, hypertension, glomerulosclerosis, and interstitial expansion were observed. H and L attenuated, but did not prevent, mortality, hypertension, and renal injury. Combined L+H treatment completely prevented mortality, normalized albuminuria and blood pressure, and arrested renal injury at levels found 1 mo after ablation, despite the unusually long period of observation. Combined L+H treatment may represent an effective therapeutic alternative to prevent progression of chronic nephropathies. PMID- 17344185 TI - Depolarization of the macula densa induces superoxide production via NAD(P)H oxidase. AB - Superoxide (O(2)(-)) enhances tubuloglomerular feedback by scavenging nitric oxide at the macula densa. However, the singling pathway of O(2)(-) production in the macula densa is not known. We hypothesized that the increase in tubular NaCl concentration that initiates tubuloglomerular feedback induces O(2)(-) production by the macula densa via NAD(P)H oxidase, which is activated by macula densa depolarization. We isolated and microperfused the thick ascending limb of the loop of Henle and attached macula densa in rabbits. A fluorescent dye, dihydroethidium, was used to detect O(2)(-) production at the macula densa. When luminal NaCl was switched from 10 to 80 mM, a situation of initiating maximum tubuloglomerular feedback response, O(2)(-) production significantly increased. To make sure that the shifts in the oxyethidium/dihydroethidium ratio were due to changes in O(2)(-), we used tempol (10(-4) M), a stable membrane-permeant superoxide dismutase mimetic. With tempol present, when we switched from 10 to 80 mM NaCl, the increase in oxyethidium/dihydroethidium ratio was blocked. To determine the source of O(2)(-), we used the NAD(P)H oxidase inhibitor apocynin. When luminal NaCl was switched from 10 to 80 mM in the presence of apocynin, O(2)(-) production was inhibited by 80%. To see whether the effect of increasing luminal NaCl involves Na-K-2Cl cotransporters, we inhibited them with furosemide. When luminal NaCl was switched from 10 to 80 mM in the presence of furosemide, O(2)(-) production was blocked. To test whether depolarization of the macula densa induces O(2)(-) production, we artificially induced depolarization by adding valinomycin (10(-6) M) and 25 mM KCl to the luminal perfusate. Depolarization alone significantly increases O(2)(-) production. We conclude that increasing luminal NaCl induces O(2)(-) production during tubuloglomerular feedback. O(2)(-) generated by the macula densa is primarily derived from NAD(P)H oxidase and is induced by depolarization. PMID- 17344186 TI - Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1 Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension. AB - Transgenic rats with inducible ANG II-dependent malignant hypertension [TGR(Cyp1a1Ren2)] were generated by inserting the mouse Ren2 renin gene into the genome of the rat. The present study was performed to assess renal morphological changes occurring during the development of ANG II-dependent malignant hypertension in these rats. Male Cyp1a1-Ren2 rats (n = 10) were fed normal rat food containing indole-3-carbinol (I3C; 0.3%) for 10 days to induce malignant hypertension. Rats induced with I3C had higher mean arterial pressures (173 +/- 9 vs. 112 +/- 11 mmHg, P < 0.01) than noninduced normotensive rats (n = 9). Glomerular damage was evaluated by determination of the glomerulosclerosis index (GSI) in tissue sections stained with periodic acid-Schiff. Kidneys of hypertensive rats had a higher GSI than normotensive rats (21.3 +/- 5.6 vs. 3.5 +/- 1.31 units). Quantitative analysis of macrophage ED-1-positive cells and proliferating cell nuclear antigen using immunohistochemistry demonstrated increased macrophage numbers in the renal interstitium (106.4 +/- 11.4 vs. 58.7 +/- 5.0 cells/mm(2)) and increased proliferating cell number in cortical tubules (37.8 +/- 5.7 vs. 24.2 +/- 2.1 cells/mm(2)), renal cortical vessels (2.2 +/- 0.5 vs. 0.13 +/- 0.07 cells/vessel), and the cortical interstitium (33.6 +/- 5.7 vs. 4.2 +/- 1.4 cells/mm(2)) of hypertensive rat kidneys. These findings demonstrate that the renal pathological changes that occur during the development of malignant hypertension in Cyp1a1-Ren2 rats are characterized by inflammation and cellular proliferation in cortical vessels and tubulointerstitium. PMID- 17344187 TI - Selective basolateral localization of overexpressed Na-K-ATPase beta1- and beta2- subunits is disrupted by butryate treatment of MDCK cells. AB - The exclusive basolateral localization of the Na-K-ATPase in kidney epithelium is a critical aspect of nephron function. It has been suggested that mislocalized delivery of the Na-K-ATPase to the apical surface in autosomal dominant polycystic kidney disease (ADPKD) is due to the inappropriate expression of an alternative isoform of the beta-subunit, the beta(2)-isoform. It has been reported that heterologous expression of this beta(2)-isoform in Madin-Darby canine kidney (MDCK) cells results in apical delivery of the Na-K-ATPase. We created a MDCK cell line containing a tetracycline-inducible promoter and expressed either myc-tagged beta(2)- or flag-tagged beta(1)-subunits to study the surface localization of these beta-subunit isoforms in polarized monolayers. We find that the beta(2)-isoform is targeted to the basolateral surface of the plasma membrane in a polarization pattern indistinguishable from the beta(1) isoform. However, inclusion of butyrate in the growth medium leads to upregulation of overexpressed beta(1)- or beta(2)-subunits and to their appearance at the apical surface. The beta(2)-isoform expressed in MDCK cells does not assemble into alpha(1)beta(2) heterodimers with the endogenous alpha(1). Our findings demonstrate that expression of the beta(2)-isoform does not lead to apical localization of the Na-K-ATPase in MDCK cells and provides evidence for an unexpected effect of butyrate on the trafficking of Na pump subunits. PMID- 17344188 TI - Role of peroxynitrite on cytoskeleton alterations and apoptosis in renal ischemia reperfusion. AB - During renal ischemia-reperfusion (I/R) injury, apoptosis has been reported as a very important contributor to final kidney damage. The determinant role of cytoskeleton derangement in the development of apoptosis has been previously reported, but a clear description of the different mechanisms involved in this process has not been yet provided. The aim of our study was to know the role of peroxynitrite as an inductor of cytoskeleton derangement and apoptosis during renal I/R. Based on a rat kidney I/R model, using experiments in which both the actin cytoskeleton and peroxynitrite generation were pharmacologically manipulated, results indicate that the peroxynitrite produced during the I/R derived oxidative stress state is able to provoke cytoskeleton derangement and apoptosis development. Thus control of peroxynitrite generation during I/R could be an effective tool for the improvement of cytoskeleton damage and reduction of apoptosis incidence in renal I/R injury. PMID- 17344189 TI - Adult-onset calorie restriction delays the accumulation of mitochondrial enzyme abnormalities in aging rat kidney tubular epithelial cells. AB - Adult-onset calorie restriction (A-CR) is an experimental model of life extension and healthy aging less explored, compared with calorie restriction begun at early ages, but one more realistic for human application. We examined the effect of A CR on the aging rat kidney with respect to common structural age-dependent changes and the accumulation of mitochondrial enzyme abnormalities in tubular epithelial cells. A 40% calorie restriction was initiated in middle-aged rats, before the onset of significant age-related changes in the Fischer x Brown Norway rat kidney. This dietary intervention effectively reduced glomerulosclerosis and tubular atrophy within 6 mo and changed the rate of interstitial fibrosis formation within 1 yr and vascular wall thickening and the expression cytochrome c oxidase (COX)-deficient tubular epithelial cells in 18 mo compared with age matched ad libitum-fed rats. Our histological approach (histochemical staining for mitochondrial enzyme activity and laser capture microdissection) coupled with mitochondrial DNA (mtDNA) PCR analyses demonstrated that COX-deficient renal tubular epithelial cells accumulated mtDNA deletion mutations and that these cells contained unique, clonally expanded mtDNA deletion mutations. Renal tubular epithelial cells with mitochondrial abnormalities presented cellular characteristics indicative of physiological dysfunction. PMID- 17344191 TI - Hepatocyte nuclear factor-4{alpha} regulates the human organic anion transporter 1 gene in the kidney. AB - Human organic anion transporter 1 (OAT1, SLC22A6), which is localized to the basolateral membranes of renal tubular epithelial cells, plays a critical role in the excretion of anionic compounds. OAT1 is regulated by various pathophysiological conditions, but little is known about the molecular mechanisms regulating the expression of OAT1. In the present study, we investigated the transcriptional regulation of OAT1 and found that hepatocyte nuclear factor (HNF) 4alpha markedly transactivated the OAT1 promoter. A deletion analysis of the OAT1 promoter suggested that the regions spanning -1191 to -700 base pairs (bp) and 140 to -79 bp were essential for the transactivation by HNF-4alpha. These regions contained a direct repeat separated by two nucleotides (DR-2), which is one of the consensus sequences binding to HNF-4alpha, and an inverted repeat separated by eight nucleotides (IR-8), which was recently identified as a novel element for HNF-4alpha, respectively. An electrophoretic mobility shift assay showed that HNF 4alpha bound to DR-2 and IR-8 under the conditions of HNF-4alpha overexpression. Furthermore, under normal conditions, HNF-4alpha bound to IR-8, and a mutation in IR-8 markedly reduced the OAT1 promoter activity, indicating that HNF-4alpha regulates the basal transcription of OAT1 via IR-8. This paper reports the first characterization of the human OAT1 promoter and the first gene in the kidney whose promoter activity is regulated by HNF-4alpha. PMID- 17344194 TI - Developing guidelines in the absence of traditional research evidence: an example from the Lymphoedema Framework Project. PMID- 17344190 TI - Neoangiogenesis and the presence of progenitor cells in the venous limb of an arteriovenous fistula in the rat. AB - Venous injury and attendant venous stenosis are major contributors to the failure of hemodialysis vascular accesses. This report describes the presence of neoangiogenesis in the intima and adventitia of the venous limb of an arteriovenous (AV) fistula in the rat, the latter induced by creating an aortocaval fistula. Immunohistochemistry of the venous limb demonstrated the presence of c-Kit-positive cells lining new microvessels with lumen formation and that these c-Kit-positive cells exhibited either a smooth muscle phenotype as reflected by concomitant expression of calponin, or an endothelial phenotype as reflected by expression of endothelial nitric oxide synthase (eNOS). Western analysis confirmed upregulation of eNOS in the venous limb of the AV fistula. Measurement of systemic concentrations of angiogenic cytokines, namely, monocyte chemotactic protein-1, stromal cell-derived factor-1 (SDF-1), cytokine-induced neutrophil chemoattractant, and VEGF, failed to reveal an increase in these cytokines either at 3 or 10 wk after creation of the AV fistula. The angiogenic cytokines VEGF and SDF-1 were not upregulated in the venous limb of the AV fistula either at 2 or 16 wk. We conclude that in this model of an AV fistula in the rat, neoangiogenesis occurs and is constituted, at least in part, by bone marrow-derived cells, the latter differentiating to exhibit either an endothelial or smooth muscle phenotype. In view of these findings, we suggest that this model may offer an experimental approach by which to explore the evolution and significance of neoangiogenesis in the formation and pathobiology of vascular plaques, and the mechanisms that promote dysfunction of hemodialysis AV fistulas. PMID- 17344192 TI - Hypotonicity stimulates renal epithelial sodium transport by activating JNK via receptor tyrosine kinases. AB - We previously reported that hypotonic stress stimulated transepithelial Na(+) transport via a pathway dependent on protein tyrosine kinase (PTK; Niisato N, Van Driessche W, Liu M, Marunaka Y. J Membr Biol 175: 63-77, 2000). However, it is still unknown what type of PTK mediates this stimulation. In the present study, we investigated the role of receptor tyrosine kinase (RTK) in the hypotonic stimulation of Na(+) transport. In renal epithelial A6 cells, we observed inhibitory effects of AG1478 [an inhibitor of the EGF receptor (EGFR)] and AG1296 [an inhibitor of the PDGF receptor (PDGFR)] on both the hypotonic stress-induced stimulation of Na(+) transport and the hypotonic stress-induced ligand independent activation of EGFR. We further studied whether hypotonic stress activates members of the MAP kinase family, ERK1/2, p38 MAPK, and JNK/SAPK, via an RTK-dependent pathway. The present study indicates that hypotonic stress induced phosphorylation of ERK1/2 and JNK/SAPK, but not p38 MAPK, that the hypotonic stress-induced phosphorylation of ERK1/2 and JNK/SAPK was diminished by coapplication of AG1478 and AG1296, and that only JNK/SAPK was involved in the hypotonic stimulation of Na(+) transport. A further study using cyclohexamide (a protein synthesis inhibitor) suggests that both RTK and JNK/SAPK contributed to the protein synthesis-independent early phase in hypotonic stress-induced Na(+) transport, but not to the protein synthesis-dependent late phase. The present study also suggests involvement of phosphatidylinositol 3-kinase (PI3-kinase) in RTK-JNK/SAPK cascade-mediated Na(+) transport. These observations indicate that 1) hypotonic stress activates JNK/SAPK via RTKs in a ligand-independent pathway, 2) the RTK-JNK/SAPK cascade acts as a mediator of hypotonic stress for stimulation of Na(+) transport, and 3) PI3-kinase is involved in the RTK-JNK/SAPK cascade for the hypotonic stress-induced stimulation of Na(+) transport. PMID- 17344195 TI - Growth factors: the promise and the problems. PMID- 17344196 TI - Optimal organization of health care in diabetic foot disease: introduction to the Eurodiale study. AB - This article describes the rationale and protocol of a large data collection study in patients with new diabetic foot ulcers by the Eurodiale study group, a consortium of centers of expertise in the field of diabetic foot disease within Europe. This study is a multicenter, observational, prospective data collection study. Its main aim is to determine the major factors determining clinical outcome and outcome in terms of health-related quality of life and health care consumption. Between September 1, 2003, and October 1, 2004, in 14 European centers, all consecutive patients with diabetes and a new foot ulcer were included in the study and followed until the end point or for a maximum of 1 year. End points were healing of the foot, major amputation, or death. Data were collected on patient, foot, and ulcer characteristics and on diagnostic and management procedures. Furthermore, data were collected on health care organization, quality of life, and resource use. A total of 1232 patients were included in the study. Sixty-three percent of the patients were referred by their general practitioner or were self-referrals. Twenty-seven percent of the patients were admitted at the time of inclusion; 1088 patients were followed until the end point. "Optimal Organization of Health Care in Diabetic Foot Disease" is one of the first large multicenter studies in the field of diabetic foot disease on clinical presentation, clinical outcome, quality of life, resource utilization, and health care organization and their interrelationships. These data will provide us with new insights that enable us to improve care for these patients and guide the development of new studies in this area. The results of this study are the subject of a separate presentation. PMID- 17344197 TI - The development and application of diabetic foot protocol in Chiang Mai University Hospital with an aim to reduce lower extremity amputation in Thai population: a preliminary communication. AB - Lower extremity amputation is a frequent complication of diabetes, and the authors' region did not have effective strategies to minimize it. From August 2005 to July 2006, a diabetic foot protocol (DFP) for out-patient management based on a multidisciplinary team approach was tried at the local teaching hospital. There are devices to reduce pressure and educate. After healing, there are custom fabricated orthoses and footwear, and monitoring of progressive ambulation. This report compares the amputation rate in patients receiving DFP care from August 2005 to July 2006 with those who had standard care from August 2003 to July 2005. Sixty-one and 110 diabetic foot ulcer patients received DFP and standard foot care, respectively. Their sex distribution and mean age were similar. The incidence of major amputations in the DFP and standard care groups was 3.3% and 13.6%, respectively (P = .03). The incidence of minor amputations in the DFP and standard care groups was 3.4% and 15.8%, respectively (P = .02). DFP was associated with improved diabetic foot care outcomes. It may be used by clinical teams with a view to improve outcomes for patients with diabetes. PMID- 17344198 TI - Clinical outcomes of wide postsurgical lesions in the infected diabetic foot managed with 2 different local treatment regimes compared using a quasi experimental study design: a preliminary communication. AB - The safety and efficacy of a novel superoxidized solution (Dermacyn Wound Care [DWC], Oculus Innovative Sciences, Petaluma, Calif) was evaluated for the treatment of wide postsurgical infected ulcers of the diabetic foot. A group (group A, n = 18) of patients with diabetes mellitus who had postsurgical lesions > 5 cm(2) without ischemia or infection were recruited consecutively and treated with DWC-saturated dressings. These dressings were renewed once daily and were compared with a group of patients that had been previously treated with diluted povidone iodine (group B, n = 15) using a quasi-experimental study design. Both sets of patients also received standard systemic antibiotic therapy, as per the practice in this center, and local surgical debridement. Patients had weekly assessments until wounds had re-epithelialized completely. Patients in group A had statistically significant shorter healing time and duration of antibiotic therapy and a higher healing rate at 6 months compared with those in group B (p < .01). Recurrence of infection, requirement for debridement procedures, and requirement for minor amputations were significantly less frequent during follow up in group A patients (p < .05) when compared with those in group B. These preliminary data suggest that DWC used as a wound dressing together with other local and systemic therapies may have a role in reducing healing time as well as complications in patients with diabetes who have postsurgical lesions of the diabetic foot. These data propose the need for a robust controlled study of DWC saturated dressings to explore its full potential. PMID- 17344199 TI - An evaluation of the value of group education in recently diagnosed diabetes mellitus. AB - Diabetic patients have a 12% to 25% lifetime risk of developing foot complications leading to significant morbidity and mortality. The objective of this study was to assess the effectiveness of group education in improving patient awareness of foot care. The authors evaluated the effect of group size and areas in which knowledge seemed to be most affected. Patients attending a 2 hour teaching session between November 2005 and March 2006 were recruited. Patients filled in an 18-part questionnaire before and after the teaching session to assess knowledge. Fifty-nine patients recently diagnosed with diabetes mellitus or foot complications were recruited for 7 sessions. Analysis of the data showed a statistically significant improvement in foot care knowledge after the teaching session compared with before (69% to 85%, P < .001). Patients in the smaller group (n < 10) had significantly higher scores compared with the bigger groups (n > 10; P < .025). These data show the benefit of group education about foot care for patients with diabetes. Smaller groups benefited more than larger ones did, which could be attributed to the sizes allowing for better interaction between the tutor and patient. As patient knowledge is variable from individual to individual, smaller teaching sessions may allow patients to address specific concerns. PMID- 17344200 TI - The diabetic foot: perspectives from Chennai, South India. AB - Foot ulcers are a significant complication of diabetes mellitus and often precede lower extremity amputation. The most frequent underlying etiologies are neuropathy, trauma, deformity, high plantar pressures, and peripheral arterial disease. Loss of protective sensation is the primary factor in foot ulceration in diabetics. Mechanical stresses resulting from joint deformity, limited joint mobility, and poor foot care/footwear are important in the causal pathway of both neuropathic and ischemic ulcers. It was shown that the recurrence of foot infection was common among Indian diabetic patients (52%). A lesser prevalence of peripheral vascular disease (13%) among Indians was noted when compared with those in Western countries (48%). Smoking increases the risk by reducing blood circulation in the legs and reducing sensation in the feet. Prompt and aggressive treatment of diabetic foot ulcers can often prevent exacerbation of the problem and eliminate the potential for amputation. The aim of the therapy should be early intervention to allow prompt healing of the lesion and prevent recurrence once it is healed. Multidisciplinary management programs that focus on prevention, education, regular foot examinations, aggressive intervention, and optimal use of therapeutic footwear have demonstrated significant reductions in the history of lower extremity amputations. PMID- 17344201 TI - Growth factors in the treatment of diabetic foot ulcers: new technologies, any promises? AB - Foot ulcers remain a common problem, leading to increased morbidity in patients with diabetes. Despite the progress that has been achieved in revascularization techniques as well as in off-loading to relieve high-pressure areas, diabetic foot wounds remain a clinical challenge. Growth factors are a major technological advance that promised to change the face of wound healing. The most important of growth factors are recombinant human platelet-derived growth factor-BB and granulocyte colony-stimulating factor. The former has been approved by the FDA for the treatment of neuropathic ulcers when there is adequate blood supply. The latter is less demonstrably useful. Advances include methods of delivering growth factors. PMID- 17344202 TI - Splenic dendritic cells pulsed with Ixodes ricinus tick saliva prime naive CD4+T to induce Th2 cell differentiation in vitro and in vivo. AB - Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) in priming naive T cells. Using an in vitro priming system, we show that DCs incubated with Ixodes ricinus tick saliva initiate the T(h)2 differentiation of CD4(+)T cells. As determined with reverse transcription-PCR, the expression of IL 4 mRNA by these cells is higher than IFN-gamma mRNA. Early endogenous production of IL-4 is thought to be important during the in vitro interaction of saliva pulsed DCs with CD4(+)T cells. Its neutralization with specific mAbs inhibits the development of IL-4-secreting T(h)2 cells. Moreover, differentiated T(h)2 cells proliferate only when saliva-pulsed DCs and IL-1beta are added together early in the primary culture. As demonstrated by FACS analysis, the treatment in vitro of saliva-pulsed DCs by IL-1beta enhanced the expression of B7 and mainly CD40 co stimulatory molecules, which provide sufficient signals to stimulate sensitized CD4(+)T cell proliferation. On the other hand, DCs treated with tick saliva only up-regulated mostly B7-2 co-stimulator expression and this was associated with differentiation of naive CD4(+)T cells into T(h)2 type of cells. The in vitro priming system is suitable to investigate the major elements implicated in the anti-tick immune response such as naive CD4(+)T cells, whole DCs population and tick saliva, and it can provide the possibility to delimit further the saliva molecules, the DC subsets and the type of host cells involved in the T(h)2 polarization. Corresponding in vivo experiments involving subcutaneous injection of tick saliva-pulsed DCs into BALB/c mice also elicited a T(h)2 immune response. Ex vivo cultures of draining lymph node T cells stimulated with tick saliva produced higher IL-4 : IFN-gamma ratios compared with controls, confirming the relevance obtained in the in vitro priming model. These experiments demonstrate the importance of tick saliva in priming DCs to initiate a T(h)2-biased immune response in vitro and in vivo. PMID- 17344203 TI - Human sexual size dimorphism in early pregnancy. AB - Sexual size dimorphism is thought to contribute to the greater mortality and morbidity of men compared with women. However, the timing of onset of sexual size dimorphism remains uncertain. The authors determined whether human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy. Using a prospective cohort study, conducted in 1999-2002 in the United States, they identified 27,655 women who conceived spontaneously and 1,008 whose conception was assisted by in vitro fertilization or intrauterine insemination and for whom a first-trimester measurement of fetal crown-rump length was available. First trimester size was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. The authors evaluated the association between fetal sex, first-trimester size, and birth weight. Eight to 12 weeks after conception, males were larger than females (mean difference: assisted conception = 0.4 days, 95% confidence interval (CI): 0.1, 0.7, p = 0.008; spontaneous conception = 0.3 days, 95% CI: 0.2, 0.4, p < 0.00001). The size discrepancy remained significant at birth (mean birth weight difference: assisted conception = 90 g, 95% CI: 22, 159, p = 0.009; spontaneous conception = 120 g, 95% CI: 107, 132, p < 0.00001). These data demonstrate that human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy. PMID- 17344204 TI - The impact of highly active antiretroviral therapy on non-AIDS-defining cancers among adults with AIDS. AB - Highly active antiretroviral therapy (HAART) has dramatically reduced the incidence of acquired immunodeficiency syndrome (AIDS) and increased AIDS survival time, but little is known about its impact on cancer. Data from adults in the San Francisco, California, AIDS surveillance registry were computer matched with the California Cancer Registry. Age-, sex-, and race-adjusted standardized incidence ratios (SIRs) were computed, and proportional hazards models evaluated the effect of HAART use on cancer incidence and cancer survival time. Among 14,210 adults with AIDS diagnosed in 1990-2000, 482 non-AIDS-defining cancers were diagnosed. Compared with rates for the general population, significantly increased cancer incidence rates were observed for anal (SIR = 13.4), Hodgkin's lymphoma (SIR = 11.5), liver (SIR = 3.6), oral cavity and pharynx (SIR = 2.6), respiratory (SIR = 2.6), leukemia (SIR = 2.4), skin melanoma (SIR = 2.4), and prostate (SIR = 1.7) cancers. Risk of liver cancer was lower with HAART use (relative hazard (RH) = 0.32). Risk of anal cancer increased after 1995 (RH = 2.9). Respiratory cancer (RH = 0.40) and Hodgkin's lymphoma (RH = 0.17) showed increased cancer survival time with HAART use, while anal cancer survival may have been slightly decreased (RH = 1.4). The impact of HAART on non AIDS-defining cancer incidence rates and survival is not uniform, and the mechanism(s) responsible for these differences should be investigated further. PMID- 17344205 TI - Patterns of alcohol drinking and all-cause mortality: results from a large-scale population-based cohort study in Japan. AB - To evaluate the hypothesis that, in terms of all-cause death, drinking alcohol 1 4 days per week is less harmful than daily (5-7 days/week) drinking of the same quantity of alcohol, a prospective cohort study using a self-administered questionnaire was conducted in Japan between 1990 and 2003 of 88,746 subjects (41,702 men and 47,044 women) aged 40-69 years at baseline. Among male regular drinkers consuming alcohol more than 1 day per week, light drinkers (<300 g/week) showed no increase in all-cause mortality irrespective of frequency of alcohol intake. Heavy drinkers (> or = 300 g/week), however, showed an increased risk of all-cause mortality among those who consumed alcohol 5-7 days per week, while no obvious increase was observed among those who consumed alcohol less than 4 days per week. Hazard ratios for drinkers who consumed alcohol 5-7 days per week were 1.29 (95% confidence interval: 1.12, 1.50) for 300-449 g per week and 1.55 (95% confidence interval: 1.32, 1.81) for > or = 450 g per week when compared with those for occasional drinkers who consumed alcohol 1-3 days per month. These findings support the Japanese social belief that "liver holidays," abstaining from alcohol for more than 2 days per week, are important for heavy drinkers. PMID- 17344206 TI - Anatomical physiology of spatial extinction. AB - Neurologically intact volunteers participated in a functional magnetic resonance imaging experiment that simulated the unilateral (focal) and bilateral (global) stimulations used to elicit extinction in patients with hemispatial neglect. In peristriate areas, attentional modulations were selectively sensitive to contralaterally directed attention. A higher level of mapping was observed in the intraparietal sulcus (IPS), inferior parietal lobule (IPL), and inferior frontal gyrus (IFG). In these areas, there was no distinction between contralateral and ipsilateral focal attention, and the need to distribute attention globally led to greater activity than either focal condition. These physiological characteristics were symmetrically distributed in the IPS and IFG, suggesting that the effects of unilateral lesions in these 2 areas can be compensated by the contralateral hemisphere. In the IPL, the greater activation by the bilateral attentional mode was seen only in the right hemisphere. Its contralateral counterpart displayed equivalent activations when attention was distributed to the right, to the left, or bilaterally. Within the context of this experiment, the IPL of the right hemisphere emerged as the one area where unilateral lesions can cause the most uncompensated and selective impairment of global attention (without interfering with unilateral attention to either side), giving rise to the phenomenon of extinction. PMID- 17344207 TI - Multiple evolutionary mechanisms drive papillomavirus diversification. AB - The circular, double-stranded 8-kb DNA genome of papillomaviruses (PVes) consists mainly of 4 large genes, E1, E2, L2, and L1. Approximately 150 papillomavirus genomes have been sequenced to date. We analyzed a representative sample of 53 PVes genomes using maximum likelihood, Bayesian inference, maximum parsimony, and distance-based methods both on nucleotide (nt) and on amino acid (aa) alignments. When the 4 genes were analyzed separately, aa-inferred phylogenies contradicted each other less than nt-inferred trees (judged by partition homogeneity tests). In particular, gene combinations including the L2 gene generated significant incongruence (P < 0.001). Combined analyses of the remaining genes E1-E2-L1 produced a well-supported phylogeny including supertaxon beta + gamma + pi + xi PVes (infecting Artiodactyla, Carnivora, Primates, and Rodentia) and supertaxon kappa + lambda + mu + nu + sigma-PVes (infecting Carnivora, Lagomorpha, Primates, and Rodentia). Based on the tree topology, host-linked evolution appears plausible at shallow, rather than deeper, taxonomic levels. Diversification within PVes may also involve adaptive radiation establishing different niches (within a single-host species) and recombination events (within single-host cells). Heterogeneous groups of closely related PVes infecting, for example, humans and domestic animals such as hamster, dog, and cattle suggest multiple infections across species borders. Additional evolutionary phenomena such as strong codon usage preferences, and computational biases including reconstruction artifacts and insufficient taxon sampling, may contribute to the incomplete resolution of deep phylogenetic nodes. The molecular data globally supports a complex evolutionary scenario for PVes, which is driven by multiple mechanisms but not exclusively by coevolution with corresponding hosts. PMID- 17344208 TI - Structure and kinetics of monofunctional proline dehydrogenase from Thermus thermophilus. AB - Proline dehydrogenase (PRODH) and Delta(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH) catalyze the two-step oxidation of proline to glutamate. They are distinct monofunctional enzymes in all eukaryotes and some bacteria but are fused into bifunctional enzymes known as proline utilization A (PutA) in other bacteria. Here we report the first structure and biochemical data for a monofunctional PRODH. The 2.0-A resolution structure of Thermus thermophilus PRODH reveals a distorted (betaalpha)(8) barrel catalytic core domain and a hydrophobic alpha-helical domain located above the carboxyl-terminal ends of the strands of the barrel. Although the catalytic core is similar to that of the PutA PRODH domain, the FAD conformation of T. thermophilus PRODH is remarkably different and likely reflects unique requirements for membrane association and communication with P5CDH. Also, the FAD of T. thermophilus PRODH is highly solvent-exposed compared with PutA due to a 4-A shift of helix 8. Structure-based sequence analysis of the PutA/PRODH family led us to identify nine conserved motifs involved in cofactor and substrate recognition. Biochemical studies show that the midpoint potential of the FAD is -75 mV and the kinetic parameters for proline are K(m) = 27 mm and k(cat) = 13 s(-1). 3,4-Dehydro-l-proline was found to be an efficient substrate, and l-tetrahydro-2-furoic acid is a competitive inhibitor (K(I) = 1.0 mm). Finally, we demonstrate that T. thermophilus PRODH reacts with O(2) producing superoxide. This is significant because superoxide production underlies the role of human PRODH in p53-mediated apoptosis, implying commonalities between eukaryotic and bacterial monofunctional PRODHs. PMID- 17344209 TI - The contribution of conformational adjustments and long-range electrostatic forces to the CD2/CD58 interaction. AB - CD2 is a T cell surface molecule that enhances T and natural killer cell function by binding its ligands CD58 (humans) and CD48 (rodents) on antigen-presenting or target cells. Here we show that the CD2/CD58 interaction is enthalpically driven and accompanied by unfavorable entropic changes. Taken together with structural studies, this indicates that binding is accompanied by energetically significant conformational adjustments. Despite having a highly charged binding interface, neither the affinity nor the rate constants of the CD2/CD58 interaction were affected by changes in ionic strength, indicating that long-range electrostatic forces make no net contribution to binding. PMID- 17344210 TI - The chromatin remodeling factor Mi-2alpha acts as a novel co-activator for human c-Myb. AB - The c-Myb protein belongs to a group of early hematopoietic transcription factors that are important for progenitor generation and proliferation. These factors have been hypothesized to participate in establishing chromatin patterns specific for hematopoietic genes. In a two-hybrid screening we identified the chromatin remodeling factor Mi-2alpha as an interaction partner for human c-Myb. The main interacting domains were mapped to the N-terminal region of Mi-2alpha and the DNA binding domain of c-Myb. Surprisingly, functional analysis revealed that Mi 2alpha, previously studied as a subunit in the NuRD co-repressor complex, enhanced c-Myb-dependent reporter activation. Consistently, knock-down of endogenous Mi-2alpha in c-Myb-expressing K562 cells, led to down-regulation of the c-Myb target genes NMU and ADA. When wild-type and helicase-dead Mi-2alpha were compared, the Myb-Mi-2alpha co-activation appeared to be independent of the ATPase/DNA helicase activity of Mi-2alpha. The rationale for the unexpected co activator function seems to lie in a dual function of Mi-2alpha, by which this factor is able to repress transcription in a helicase-dependent and activate in a helicase-independent fashion, as revealed by Gal4-tethering experiments. Interestingly, desumoylation of c-Myb potentiated the Myb-Mi-2alpha transactivational co-operation, as did co-transfection with p300. PMID- 17344211 TI - Oct4 and Sox2 directly regulate expression of another pluripotency transcription factor, Zfp206, in embryonic stem cells. AB - It is well known that Oct4 and Sox2 play an important role in the maintenance of embryonic stem cell pluripotency. These transcription factors bind to regulatory regions within hundreds of target genes to control their expression. Zfp206 is a recently characterized transcription factor that has a role in maintaining stem cell pluripotency. We have demonstrated here that Zfp206 is a direct downstream target of Oct4 and Sox2. Two composite sox-oct binding sites have been identified within the first intron of Zfp206. We have demonstrated binding of Oct4 and Sox2 to this region. In addition, we have shown that Oct4 or Sox2 alone can activate transcription via one of these sox-oct elements, although the presence of both Oct4 and Sox2 gave rise to a synergistic effect. These studies extend our understanding of the transcriptional network that operates to regulate the differentiation potential of embryonic stem cells. PMID- 17344212 TI - Shedding of syndecan-1 by stromal fibroblasts stimulates human breast cancer cell proliferation via FGF2 activation. AB - The cell surface heparan sulfate proteoglycan syndecan-1 is induced in stromal fibroblasts of breast carcinomas and participates in a reciprocal feedback loop, which stimulates carcinoma cell growth in vitro and in vivo. To define the molecular mechanism of carcinoma growth stimulation, a three-dimensional co culture model was developed that combines T47D breast carcinoma cells with immortalized human mammary fibroblasts in collagen gels. By silencing endogenous syndecan-1 induction with short interfering RNA and expressing mutant murine syndecan-1 constructs, it was determined that carcinoma cell mitogenesis required proteolytic shedding of syndecan-1 from the fibroblast surface. The paracrine growth signal was mediated by the syndecan-1 heparan lfate chains rather than the ectodomain of the core protein and required fibroblast growth factor 2 and stroma derived factor 1. This paracrine pathway may provide an opportunity for the therapeutic disruption of stromaepithelial signaling. PMID- 17344213 TI - Desmoglein versus non-desmoglein signaling in pemphigus acantholysis: characterization of novel signaling pathways downstream of pemphigus vulgaris antigens. AB - Although it is accepted that pemphigus antibody binding to keratinocytes (KCs) evokes an array of intracellular biochemical events resulting in cell detachment and death, the triggering events remain obscure. It has been postulated that the binding of pemphigus vulgaris IgG (PVIgG) to KCs induces "desmosomal" signaling. Because in contrast to integrins and classical cadherins, desmoglein (Dsg) molecules are not known to elicit intracellular signaling, and because PV patients also produce non-Dsg autoantibodies, we investigated the roles of both Dsg and non-desmoglein PV antigens. The time course studies of KCs treated with PVIgG demonstrated that the activity of Src peaked at 30 min, EGF receptor kinase (EGFRK) at 60 min, and p38 MAPK at 240 min. The Src inhibitor PP2 decreased EGFRK and p38 activities by approximately 45 and 30%, respectively, indicating that in addition to Src, PVIgG evokes other triggering events. The shrinkage of KCs (cell volume reduction) became significant at 120 min, keratin aggregation at 240 min, and an increase of TUNEL positivity at 360 min. Pretreatment of KCs with PP2 blocked PVIgG-dependent cell shrinkage and keratin aggregation by approximately 50% and TUNEL positivity by approximately 25%. The p38 MAPK inhibitor PD169316 inhibited these effects by approximately 15, 20, and 70%, respectively. Transfection of KCs with small interfering RNAs that silenced expression of Dsg1 and/or Dsg3 proteins, blocked approximately 50% of p38 MAPK activity but did not significantly alter the PVIgG-dependent rise in Src and EGFRK activities. These results indicate that activation of p38 MAPK is a late signaling step associated with collapse of the cytoskeleton and disassembly of desmosomes caused by upstream events involving Src and EGFRK. Therefore, the early acantholytic events are triggered by non-Dsg antibodies. PMID- 17344215 TI - The role of disulfide bonds and alpha-helical coiled-coils in the biosynthesis of type XIII collagen and other collagenous transmembrane proteins. AB - Type XIII collagen is a type II transmembrane protein with three collagenous (COL1-3) and four noncollagenous domains (NC1-4). The human alpha1(XIII) chain contains altogether eight cysteine residues. We introduced point mutations to six of the most N-terminal cysteine residues, and we show here that the two cysteines 117 and 119 at the end of the N-terminal noncollagenous domain (NC1) are responsible for linking the three alpha1(XIII) chains together by means of interchain disulfide bonds. In addition, the intracellular and transmembrane domains have an impact on trimer formation, whereas the cysteines in the transmembrane domain and the COL1, the NC2, and the C-terminal NC4 domains do not affect trimer formation. We also suggest that the first three noncollagenous domains (NC1-3) harbor repeating heptad sequences typical of alpha-helical coiled coils, whereas the conserved NC4 lacks a coiled-coil probability. Prevention of the coiled-coil conformation in the NC3 domain is shown here to result in labile type XIII collagen molecules. Furthermore, a new subgroup of collagenous transmembrane proteins, the Rattus norvegicus, Drosophila melanogaster, and Caenorhabditis elegans colmedins, is enlarged to contain also Homo sapiens collomin, and Pan troglodytes, Mus musculus, Tetraodon nigroviridis, and Dano rerio proteins. We suggest that there is a structurally varied group of collagenous transmembrane proteins whose biosynthesis is characterized by a coiled-coil motif following the transmembrane domain, and that these trimerization domains appear to be associated with each of the collagenous domains. In the case of type XIII collagen, the trimeric molecule has disulfide bonds at the junction of the NC1 and COL1 domains, and the type XIII collagen like molecules (collagen types XXIII and XXV) and the colmedins are similar in that they all have a pair of cysteines in the same location. Moreover, furin cleavage at the NC1 domain can be expected in most of the proteins. PMID- 17344214 TI - leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3. AB - Numerous epidemiological studies documented that obesity is a risk factor for breast cancer development in postmenopausal women. Leptin, the key player in the regulation of energy balance and body weight control also acts as a growth factor on certain organs in both normal and disease state. In this study, we analyzed the role of leptin and the molecular mechanism(s) underlying its action in breast cancer cells that express both short and long isoforms of leptin receptor. Leptin increased MCF7 cell population in the S-phase of the cell cycle along with a robust increase in CYCLIN D1 expression. Also, leptin induced Stat3 phosphorylation-dependent proliferation of MCF7 cells as blocking Stat3 phosphorylation with a specific inhibitor, AG490, abolished leptin-induced proliferation. Using deletion constructs of CYCLIN D1 promoter and chromatin immunoprecipitation assay, we show that leptin induced increase in CYCLIN D1 promoter activity is mediated through binding of activated Stat3 at the Stat binding sites and changes in histone acetylation and methylation. We also show specific involvement of coactivator molecules, histone acetyltransferase SRC1, and mediator complex in leptin-mediated regulation of CYCLIN D1 promoter. Importantly, silencing of SRC1 and Med1 abolished the leptin induced increase in CYCLIN D1 expression and MCF7 cell proliferation. Intriguingly, recruitment of both SRC1 and Med1 was dependent on phosphorylated Stat3 as AG490 treatment inhibited leptin-induced recruitment of these coactivators to CYCLIN D1 promoter. Our data suggest that CYCLIN D1 may be a target gene for leptin mediated growth stimulation of breast cancer cells and molecular mechanisms involve activated Stat3-mediated recruitment of distinct coactivator complexes. PMID- 17344216 TI - Transcription factor PHOX2A regulates the human alpha3 nicotinic receptor subunit gene promoter. AB - PHOX2A is a paired-like homeodomain transcription factor that participates in specifying the autonomic nervous system. It is also involved in the transcriptional control of the noradrenergic neurotransmitter phenotype as it regulates the gene expression of tyrosine hydroxylase and dopamine-beta hydroxylase. The results of this study show that the human orthologue of PHOX2A is also capable of regulating the transcription of the human alpha3 nicotinic acetylcholine receptor gene, which encodes the ligand-binding subunit of the ganglionic type nicotinic receptor. In particular, we demonstrated by chromatin immunoprecipitation and DNA pulldown assays that PHOX2A assembles on the SacI NcoI region of alpha3 promoter and, by co-transfection experiments, that it exerts its transcriptional effects by acting through the 60-bp minimal promoter. PHOX2A does not seem to bind to DNA directly, and its DNA binding domain seems to be partially dispensable for the regulation of alpha3 gene transcription. However, as suggested by the findings of our co-immunoprecipitation assays, it may establish direct or indirect protein-protein interactions with Sp1, thus regulating the expression of alpha3 through a DNA-independent mechanism. As the alpha3 subunit is expressed in every terminally differentiated ganglionic cell, this is the first example of a "pan-autonomic" gene whose expression is regulated by PHOX2 proteins. PMID- 17344217 TI - MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts. AB - We have previously found that the ether-a-go-go related gene (ERG), a long QT syndrome gene encoding a key K(+) channel (I(Kr)) in cardiac cells, is severely depressed in its expression at the protein level but not at the mRNA level in diabetic subjects. The mechanisms underlying the disparate alterations of ERG protein and mRNA, however, remained unknown. We report here a remarkable overexpression of miR-133 in hearts from a rabbit model of diabetes, and in parallel the expression of serum response factor (SRF), which is known to be a transactivator of miR-133, was also robustly increased. Delivery of exogenous miR 133 into the rabbit myocytes and cell lines produced post-transcriptional repression of ERG, down-regulating ERG protein level without altering its transcript level and caused substantial depression of I(Kr), an effect abrogated by the miR-133 antisense inhibitor. Functional inhibition or gene silencing of SRF down-regulated miR-133 expression and increased I(Kr) density. Repression of ERG by miR-133 likely underlies the differential changes of ERG protein and transcript thereby depression of I(Kr), and contributes to repolarization slowing thereby QT prolongation and the associated arrhythmias, in diabetic hearts. Our study provided the first evidence for the pathological role of miR-133 in adult hearts and thus expanded our understanding of the cellular function and pathophysiological roles of miRNAs. PMID- 17344218 TI - Vps75, a new yeast member of the NAP histone chaperone family. AB - Homologues of nucleosome assembly protein 1 (NAP1) are found throughout eukaryotes. Here we identify and characterize a new NAP family histone chaperone from budding yeast, named Vps75. Purified Vps75 preferentially binds histone H3/H4 tetramers and is capable of assembling nucleosomes in vitro. In vivo, Vps75 is associated with the chromatin of both active and inactive genes and telomeres. Others have previously reported that Vps75 forms a complex with Rtt109, required for acetylation of histone H3 lysine 56 (H3 Lys-56). Cells lacking RTT109 are sensitive to hydroxyurea, pointing to a role in replication. We show that VPS75 is not required for H3 Lys-56 acetylation and that vps75Delta cells are insensitive to hydroxyurea, suggesting that although Rtt109 and Vps75 associate and are likely to be functionally connected, they also have separate roles. PMID- 17344219 TI - Clathrin adaptor GGA1 polymerizes clathrin into tubules. AB - GGAs, a class of monomeric clathrin adaptors, are involved in the sorting of cargo at the trans-Golgi network of eukaryotic cells. They are modular structures consisting of the VHS, the GAT, hinge, and GAE domains, which have been shown to interact directly with cargo, ARF, clathrin, and accessory proteins, respectively. Previous studies have shown that GGAs interact with clathrin both in solution and in the cell, but it has yet been shown whether they assemble clathrin. We find that GGA1 promoted assembly of clathrin with complete assembly achieved when one GGA1 molecule is bound per heavy chain. In the presence of excess GGA1, we obtained the unusual stoichiometry of five GGA1s per heavy chain, and even at this stoichiometry the binding was not saturated. The assembled structures were mostly baskets, but approximately 10% of the structures were tubular with an average length of 180 +/- 40 nm and width of approximately 50 nm. The truncated GGA1 fragment consisting of the hinge+GAE domains bound to clathrin with similar affinity as the full-length molecule and polymerized clathrin into baskets. Unlike the full-length molecule, this fragment saturated the lattices at one molecule per heavy chain and assembled clathrin only into baskets. The separated hinge and GAE domains bound much weaker to clathrin than the intact molecule, and these domains do not significantly polymerize clathrin into baskets. We conclude that clathrin adaptor GGA1 is a clathrin assembly protein, but it is unique in its ability to polymerize clathrin into tubules. PMID- 17344220 TI - Functional and structural characterization of the first prokaryotic member of the L-amino acid transporter (LAT) family: a model for APC transporters. AB - We have identified YkbA from Bacillus subtilis as a novel member of the L-amino acid transporter (LAT) family of amino acid transporters. The protein is approximately 30% identical in amino acid sequence to the light subunits of human heteromeric amino acid transporters. Purified His-tagged YkbA from Escherichia coli membranes reconstituted in proteoliposomes exhibited sodium-independent, obligatory exchange activity for L-serine and L-threonine and also for aromatic amino acids, albeit with less activity. Thus, we propose that YkbA be renamed SteT (Ser/Thr exchanger transporter). Kinetic analysis supports a sequential mechanism of exchange for SteT. Freeze-fracture analysis of purified, functionally active SteT in proteoliposomes, together with blue native polyacrylamide gel electrophoresis and transmission electron microscopy of detergent-solubilized purified SteT, suggest that the transporter exists in a monomeric form. Freeze-fracture analysis showed spherical particles with a diameter of 7.4 nm. Transmission electron microscopy revealed elliptical particles (diameters 6 x 7 nm) with a distinct central depression. To our knowledge, this is the first functional characterization of a prokaryotic member of the LAT family and the first structural data on an APC (amino acids, polyamines, and choline for organocations) transporter. SteT represents an excellent model to study the molecular architecture of the light subunits of heteromeric amino acid transporters and other APC transporters. PMID- 17344221 TI - ATP binding to the KTN/RCK subunit KtrA from the K+ -uptake system KtrAB of Vibrio alginolyticus: its role in the formation of the KtrAB complex and its requirement in vivo. AB - Subunit KtrA of the bacterial Na(+)-dependent K(+)-translocating KtrAB systems belongs to the KTN/RCK family of regulatory proteins and protein domains. They are located at the cytoplasmic side of the cell membrane. By binding ligands they regulate the activity of a number of K(+) transporters and K(+) channels. To investigate the function of KtrA from the bacterium Vibrio alginolyticus (VaKtrA), the protein was overproduced in His-tagged form (His(10)-VaKtrA) and isolated by affinity chromatography. VaKtrA contains a G-rich, ADP-moiety binding beta-alpha-beta-fold ("Rossman fold"). Photocross-linking and flow dialysis were used to determine the binding of [(32)P]ATP and [(32)P]NAD(+) to His(10)-VaKtrA. Binding of other nucleotides was estimated from the competition by these compounds of the binding of the (32)P-labeled nucleotides to the protein. [gamma (32)P]ATP bound with high affinity to His(10)-VaKtrA (K(D) of 9 microm). All other nucleotides tested exhibited K(D) (K(i)) values of 30 microm or higher. Limited proteolysis with trypsin showed that ATP was the only nucleotide that changed the conformation of VaKtrA. ATP specifically promoted complex formation of VaKtrA with the His-tagged form of its K(+)-translocating partner, VaKtrB His(6), as detected both in an overlay experiment and in an experiment in which VaKtrA was added to VaKtrB-His(6) bound to Ni(2+)-agarose. In intact cells of Escherichia coli both a high of membrane potential and a high cytoplasmic ATP concentration were required for VaKtrAB activity. C-terminal deletions in VaKtrA showed that for in vivo activity at least 169 N-terminal amino acid residues of its total of 220 are required and that its 40 C-terminal residues are dispensable. PMID- 17344222 TI - EGLN3 prolyl hydroxylase regulates skeletal muscle differentiation and myogenin protein stability. AB - EGLN3, a member of the EGLN family of prolyl hydroxylases, has been shown to catalyze hydroxylation of the alpha subunit of hypoxia-inducible factor-alpha, which targets hypoxia-inducible factor-alpha for ubiquitination by a ubiquitin ligase complex containing the von Hippel-Lindau (VHL) tumor suppressor. We now report that EGLN3 levels increase during C2C12 skeletal myoblast differentiation. EGLN3 small interference RNAs and EGLN3 antisense oligonucleotides blocked C2C12 differentiation and decreased levels of myogenin, a member of the MyoD family of myogenic regulatory factors, which plays a critical role in myogenic differentiation. We also report that EGLN3 interacts with and stabilizes myogenin protein, whereas VHL associates with and destabilizes myogenin via the ubiquitin proteasome system. The effect of VHL on myogenin stability and ubiquitination can be reversed, at least in part, by overexpression of EGLN3, suggesting that its binding to myogenin may prevent VHL-mediated degradation. These data demonstrate a novel role for EGLN3 in regulating skeletal muscle differentiation and gene expression. In addition, this report provides evidence for a novel pathway that regulates myogenin expression and skeletal muscle differentiation. PMID- 17344223 TI - Ochratoxin A: 13-week oral toxicity and cell proliferation in male F344/n rats. AB - Ochratoxin A (OTA) is nephrotoxic and a potent renal carcinogen. Male rats are most susceptible to OTA toxicity, and chronic administration of OTA (70 and 210 microg/kg bw) for 2 years has been shown to induce high incidences of adenomas and carcinomas arising from the straight segment of the proximal tubule epithelium. In contrast, treatment with a lower dose of 21 microg/kg bw did not result in increased tumor rates, suggesting a nonlinear dose response for renal tumor formation by OTA. Since the mechanism of OTA carcinogenicity is still largely unknown, this study was conducted to investigate early functional and pathological effects of OTA and to determine if sustained stimulation of renal cell proliferation plays a role. Male F344/N rats were treated with OTA for up to 13 weeks under conditions of the National Toxicology Program (NTP) bioassay. Cell proliferation in the renal cortex and outer stripe of the outer medulla (OSOM) was determined using bromodeoxyuridine incorporation and immunohistochemistry. Histopathological examination showed renal alterations in mid- and high-dose treated animals involving single-cell death and prominent nuclear enlargement within the straight proximal tubules. Treatment with OTA at doses of 70 and 210 microg/kg bw led to a marked dose- and time-dependent increase in renal cell proliferation, extending from the medullary rays into the OSOM. No effects were evident in kidneys of low-dose-treated animals or in the liver, which is not a target for OTA carcinogenicity. A no observed effect level in this study was established at 21 microg/kg bw, correlating with the dose in the NTP 2-year bioassay that did not produce renal tumors. The apparent correlation between enhanced cell turnover and tumor formation induced by OTA indicates that stimulation of cell proliferation may play an important role in OTA carcinogenicity and provides further evidence for an epigenetic, thresholded mechanism. PMID- 17344224 TI - Subfecundity in overweight and obese couples. AB - BACKGROUND: Recent studies indicate that not only women's but also men's obesity has adverse effects on fecundity and since fecundity is a couple concept, we examined fecundity in relation to overweight and obesity of the couple. We also examined the association between weight changes and fecundity over time. METHODS: Between 1996 and 2002, 64 167 pregnant women enrolled in the Danish National Birth Cohort were interviewed during and 18 months after pregnancy. Information on body mass index (BMI) and waiting time to pregnancy (TTP) was available for 47 835 couples. RESULTS: Among men and women with a BMI of 18.5 kg/m(2) or more, we found a dose-response relationship between increasing BMI group and subfecundity (a TTP of more than 12 months): Odds ratio (OR) = 1.32 (95% CI: 1.26-1.37) for women and OR = 1.19 (95% CI: 1.14-1.24) for men. Among 2374 women with an initial BMI of 18.5 kg/m(2) or more, who participated more than once in the Danish National Birth Cohort, each kilogram increment in weight between the two pregnancies was associated with a 2.84 (95% CI: 1.33-4.35) days longer TTP. CONCLUSIONS: Couples have a high risk of being subfecund if they are both obese. PMID- 17344225 TI - Ephrin-Eph signalling drives the asymmetric division of notochord/neural precursors in Ciona embryos. AB - Asymmetric cell divisions produce two sibling cells with distinct fates, providing an important means of generating cell diversity in developing embryos. Many examples of such cell divisions have been described, but so far only a limited number of the underlying mechanisms have been elucidated. Here, we have uncovered a novel mechanism controlling an asymmetric cell division in the ascidian embryo. This division produces one notochord and one neural precursor. Differential activation of extracellular-signal-regulated kinase (ERK) between the sibling cells determines their distinct fates, with ERK activation promoting notochord fate. We first demonstrate that the segregation of notochord and neural fates is an autonomous property of the mother cell and that the mother cell acquires this functional polarity via interactions with neighbouring ectoderm precursors. We show that these cellular interactions are mediated by the ephrin Eph signalling system, previously implicated in controlling cell movement and adhesion. Disruption of contacts with the signalling cells or inhibition of the ephrin-Eph signal results in the symmetric division of the mother cell, generating two notochord precursors. Finally, we demonstrate that the ephrin-Eph signal acts via attenuation of ERK activation in the neural-fated daughter cell. We propose a model whereby directional ephrin-Eph signals functionally polarise the notochord/neural mother cell, leading to asymmetric modulation of the FGF-Ras ERK pathway between the daughter cells and, thus, to their differential fate specification. PMID- 17344226 TI - Synthesis of the sulfate donor PAPS in either the Drosophila germline or somatic follicle cells can support embryonic dorsal-ventral axis formation. AB - The establishment of dorsal-ventral (DV) polarity in the Drosophila embryo depends upon a localized signal that is generated in the perivitelline space of the egg through the action of a serine proteolytic cascade. Spatial regulation of this pathway is determined by the expression of the pipe gene in a subpopulation of ventral follicle cells in the developing egg chamber. The Pipe protein exhibits homology to vertebrate glycosaminoglycan sulfotransferases. In a previous study, we demonstrated that embryonic DV polarity depends upon the sulfotransferase activity of Pipe. Surprisingly, however, our results also indicated that formation of the embryonic DV axis does not require the synthesis of the high-energy sulfate donor, 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in the follicle cells in which Pipe is presumed to function. Here, we resolve this apparent paradox by demonstrating that dorsalized embryos are only produced by egg chambers in which both germline and follicle cells lack PAPS synthetase activity. Thus, PAPS produced either in the germline or in the follicular epithelium can support the requirement for Pipe sulfotransferase activity in embryonic DV patterning. This finding indicates the existence of a conduit for the movement of PAPS between the germline and the follicle cells, which highlights a previously unappreciated mechanism of soma/germline cooperation affecting pattern formation. PMID- 17344228 TI - Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development. AB - Cardiac outflow tract (OFT) septation is crucial to the formation of the aortic and pulmonary arteries. Defects in the formation of the OFT can result in serious congenital heart defects. Two cell populations, the anterior heart field (AHF) and cardiac neural crest cells (CNCCs), are crucial for OFT development and septation. In this study, we use a series of tissue-specific genetic manipulations to define the crucial role of the Hedgehog pathway in these two fields of cells during OFT development. These data indicate that endodermally produced SHH ligand is crucial for several distinct processes, all of which are required for normal OFT septation. First, SHH is required for CNCCs to survive and populate the OFT cushions. Second, SHH mediates signaling to myocardial cells derived from the AHF to complete septation after cushion formation. Finally, endodermal SHH signaling is required in an autocrine manner for the survival of the pharyngeal endoderm, which probably produces a secondary signal required for AHF survival and for OFT lengthening. Disruption of any of these steps can result in a single OFT phenotype. PMID- 17344227 TI - Snail2 directly represses cadherin6B during epithelial-to-mesenchymal transitions of the neural crest. AB - The neural crest, a transient population of migratory cells, forms the craniofacial skeleton and peripheral nervous system, among other derivatives in vertebrate embryos. The transcriptional repressor Snail2 is thought to be crucial for the epithelial-to-mesenchymal transition (EMT) that promotes neural crest delamination from the neural tube; however, little is known about its downstream targets. To this end, we depleted avian Snail2 in the premigratory neural crest using morpholino antisense oligonucleotides and examined effects on potential targets by quantitative PCR. Several dorsal neural tube genes were upregulated by alleviating Snail2 repression; moreover, the cell adhesion molecule cadherin6B was derepressed within 30 minutes of blocking Snail2 translation. Examination of the chick cadherin6B genomic sequence reveals that the regulatory region contains three pairs of clustered E boxes, representing putative Snail2 binding sites. Furthermore, in vivo and in vitro biochemical analyses demonstrate that Snail2 directly binds to these sites and regulates cadherin6B transcription. These results are the first to describe a direct target of Snail2 repression in vivo and in the context of the EMT that characterizes neural crest development. PMID- 17344229 TI - Stonewalling Drosophila stem cell differentiation by epigenetic controls. AB - During Drosophila oogenesis, germline stem cell (GSC) identity is maintained largely by preventing the expression of factors that promote differentiation. This is accomplished via the activity of several genes acting either in the GSC or in its niche. The translational repressors Nanos and Pumilio act in GSCs to prevent differentiation, probably by inhibiting the translation of early differentiation factors, whereas niche signals prevent differentiation by silencing transcription of the differentiation factor Bam. We have found that the DNA-associated protein Stonewall (Stwl) is also required for GSC maintenance. stwl is required cell-autonomously; clones of stwl(-) germ cells were lost by differentiation, and ectopic Stwl caused an expansion of GSCs. stwl mutants acted as Suppressors of variegation, indicating that stwl normally acts in chromatin dependent gene repression. In contrast to several previously described GSC maintenance factors, Stwl probably functions epigenetically to prevent GSC differentiation. Stwl-dependent transcriptional repression does not target bam, but rather Stwl represses the expression of many genes, including those that may be targeted by Nanos and Pumilio translational inhibition. PMID- 17344230 TI - Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord. AB - During development, the three major neural cell lineages, neurons, oligodendrocytes and astrocytes, differentiate in specific temporal orders at topologically defined positions. How the timing and position of their generation are coordinately regulated remains poorly understood. Here, we provide evidence that the transcription factors Pax6, Olig2 and Nkx2.2 (Nkx2-2), which define the positional identity of multipotent progenitors early in development, also play crucial roles in controlling the timing of neurogenesis and gliogenesis in the developing ventral spinal cord. We show that each of these factors has a unique ability to either enhance or inhibit the activities of the proneural helix-loop helix (HLH) factors Ngn1 (Neurog1), Ngn2 (Neurog2), Ngn3 (Neurog3) and Mash1 (Ascl1), and the inhibitory HLH factors Id1 and Hes1, thereby regulating both the timing of differentiation of multipotent progenitors and their fate. Consistent with this, dynamic changes in their co-expression pattern in vivo are closely correlated to stage- and domain-specific generation of three neural cell lineages. We also show that genetic manipulations of their temporal expression patterns in mice alter the timing of differentiation of neurons and glia. We propose a molecular code model whereby the combinatorial actions of two classes of transcription factors coordinately regulate the domain-specific temporal sequence of neurogenesis and gliogenesis in the developing spinal cord. PMID- 17344231 TI - Foxe view of lens development and disease. AB - The recent identification of a mutation in Foxe3 that causes congenital primary aphakia in humans marks an important milestone. Congenital primary aphakia is a rare developmental disease in which the lens does not form. Previously, Foxe3 had been shown to play a crucial role in vertebrate lens formation and this gene is one of the earliest integrators of several signaling pathways that cooperate to form a lens. In this review, we highlight recent advances that have led to a better understanding of the developmental processes and gene regulatory networks involved in lens development and disease. PMID- 17344232 TI - Glycan classification with tree kernels. AB - MOTIVATION: Glycans are covalent assemblies of sugar that play crucial roles in many cellular processes. Recently, comprehensive data about the structure and function of glycans have been accumulated, therefore the need for methods and algorithms to analyze these data is growing fast. RESULTS: This article presents novel methods for classifying glycans and detecting discriminative glycan motifs with support vector machines (SVM). We propose a new class of tree kernels to measure the similarity between glycans. These kernels are based on the comparison of tree substructures, and take into account several glycan features such as the sugar type, the sugar bound type or layer depth. The proposed methods are tested on their ability to classify human glycans into four blood components: leukemia cells, erythrocytes, plasma and serum. They are shown to outperform a previously published method. We also applied a feature selection approach to extract glycan motifs which are characteristic of each blood component. We confirmed that some leukemia-specific glycan motifs detected by our method corresponded to several results in the literature. AVAILABILITY: Softwares are available upon request. SUPPLEMENTARY INFORMATION: Datasets are available at the following website: http://web.kuicr.kyoto-u.ac.jp/supp/yoshi/glycankernel/ PMID- 17344233 TI - BioGuideSRS: querying multiple sources with a user-centric perspective. AB - Biologists are frequently faced with the problem of integrating information from multiple heterogeneous sources with their own experimental data. Given the large number of public sources, it is difficult to choose which sources to integrate without assistance. When doing this manually, biologists differ in their preferences concerning the sources to be queried as well as the strategies, i.e. the querying process they follow for navigating through the sources. In response to these findings, we have developed BioGuide to assist scientists search for relevant data within external sources while taking their preferences and strategies into account. In this article, we present BioGuideSRS, a user-friendly system which automatically retrieves instances of data by using BioGuide on top of the sequence retrieval system (SRS). BioGuideSRS is an Applet that can be run from its web page on any system with Java 5.0. AVAILABILITY: http://www.bioguide project.net. PMID- 17344234 TI - A new method to measure the semantic similarity of GO terms. AB - MOTIVATION: Although controlled biochemical or biological vocabularies, such as Gene Ontology (GO) (http://www.geneontology.org), address the need for consistent descriptions of genes in different data sources, there is still no effective method to determine the functional similarities of genes based on gene annotation information from heterogeneous data sources. RESULTS: To address this critical need, we proposed a novel method to encode a GO term's semantics (biological meanings) into a numeric value by aggregating the semantic contributions of their ancestor terms (including this specific term) in the GO graph and, in turn, designed an algorithm to measure the semantic similarity of GO terms. Based on the semantic similarities of GO terms used for gene annotation, we designed a new algorithm to measure the functional similarity of genes. The results of using our algorithm to measure the functional similarities of genes in pathways retrieved from the saccharomyces genome database (SGD), and the outcomes of clustering these genes based on the similarity values obtained by our algorithm are shown to be consistent with human perspectives. Furthermore, we developed a set of online tools for gene similarity measurement and knowledge discovery. AVAILABILITY: The online tools are available at: http://bioinformatics.clemson.edu/G-SESAME. SUPPLEMENTARY INFORMATION: http://bioinformatics.clemson.edu/Publication/Supplement/gsp.htm. PMID- 17344235 TI - ABCGrid: Application for Bioinformatics Computing Grid. AB - We have developed a package named Application for Bioinformatics Computing Grid (ABCGrid). ABCGrid was designed for biology laboratories to use heterogeneous computing resources and access bioinformatics applications from one master node. ABCGrid is very easy to install and maintain at the premise of robustness and high performance. We implement a mechanism to install and update all applications and databases in worker nodes automatically to reduce the workload of manual maintenance. We use a backup task method and self-adaptive job dispatch approach to improve performance. Currently, ABCGrid integrates NCBI_BLAST, Hmmpfam and CE, running on a number of computing platforms including UNIX/Linux, Windows and Mac OS X. AVAILABILITY: The source code, executables and documents can be downloaded from http://abcgrid.cbi.pku.edu.cn PMID- 17344236 TI - EuSplice: a unified resource for the analysis of splice signals and alternative splicing in eukaryotic genes. AB - MOTIVATION: Despite increased availability of genome annotation data, a comprehensive resource for in-depth analysis of splice signal distributions and alternative splicing (AS) patterns in eukaryote genomes is still lacking. To meet this need, we have developed EuSplice--a unique splice-centric database which provides reliable splice signal and AS information for 23 eukaryotes. RESULTS: The EuSplice database contains 95,822 AS events and 2.1 million splice signals associated with over 270,000 protein-coding genes. The intuitive, user-friendly EuSplice web interface has powerful data mining and graphics capabilities for inter-genomic comparative analysis of splice signals, putative cryptic splice sites and AS events. Moreover, the seamless integration of splicing data to extensive gene-specific annotations, such as homolog annotations, functional information, mutations and sequence details makes EuSplice a powerful one-stop information resource for investigating the molecular mechanisms of complex splicing events, disease associations and the evolution of splicing in eukaryotes. AVAILABILITY: http://66.170.16.154/EuSplice. SUPPLEMENTARY INFORMATION: Supplementary tables and figures at Bioinfo online. PMID- 17344237 TI - Metabolic systems cost-benefit analysis for interpreting network structure and regulation. AB - MOTIVATION: Interpretation of bioinformatics data in terms of cellular function is a major challenge facing systems biology. This question is complicated by robust metabolic networks filled with structural features like parallel pathways and isozymes. Under conditions of nutrient sufficiency, metabolic networks are well known to be regulated for thermodynamic efficiency however; efficient biochemical pathways are anabolically expensive to construct. While parameters like thermodynamic efficiency have been extensively studied, a systems-based analysis of anabolic proteome synthesis 'costs' and the cellular function implications of these costs has not been reported. RESULTS: A cost-benefit analysis of an in silico Escherichia coli network revealed the relationship between metabolic pathway proteome synthesis requirements, DNA-coding sequence length, thermodynamic efficiency and substrate affinity. The results highlight basic metabolic network design principles. Pathway proteome synthesis requirements appear to have shaped biochemical network structure and regulation. Under conditions of nutrient scarcity and other general stresses, E. coli expresses pathways with relatively inexpensive proteome synthesis requirements instead of more efficient but also anabolically more expensive pathways. This evolutionary strategy provides a cellular function-based explanation for common network motifs like isozymes and parallel pathways and possibly explains 'overflow' metabolisms observed during nutrient scarcity. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 17344238 TI - Pooling mRNA in microarray experiments and its effect on power. AB - MOTIVATION: Microarrays can simultaneously measure the expression levels of many genes and are widely applied to study complex biological problems at the genetic level. To contain costs, instead of obtaining a microarray on each individual, mRNA from several subjects can be first pooled and then measured with a single array. mRNA pooling is also necessary when there is not enough mRNA from each subject. Several studies have investigated the impact of pooling mRNA on inferences about gene expression, but have typically modeled the process of pooling as if it occurred in some transformed scale. This assumption is unrealistic. RESULTS: We propose modeling the gene expression levels in a pool as a weighted average of mRNA expression of all individuals in the pool on the original measurement scale, where the weights correspond to individual sample contributions to the pool. Based on these improved statistical models, we develop the appropriate F statistics to test for differentially expressed genes. We present formulae to calculate the power of various statistical tests under different strategies for pooling mRNA and compare resulting power estimates to those that would be obtained by following the approach proposed by Kendziorski et al. (2003). We find that the Kendziorski estimate tends to exceed true power and that the estimate we propose, while somewhat conservative, is less biased. We argue that it is possible to design a study that includes mRNA pooling at a significantly reduced cost but with little loss of information. PMID- 17344239 TI - Analyzing microarray data using CLANS. AB - Analysis of microarray experiments is complicated by the huge amount of data involved. Searching for groups of co-expressed genes is akin to searching for protein families in a database as, in both cases, small subsets of genes with similar features are to be found within vast quantities of data. CLANS was originally developed to find protein families in large sets of amino acid sequences where the amount of data involved made phylogenetic approaches overly cumbersome. We present a number of improvements that greatly extend the previous version of CLANS and show its application to microarray data as well as its ability of incorporating additional information to facilitate interactive analysis. AVAILABILITY: The program is available for download from: http://bioinfoserver.rsbs.anu.edu.au/downloads/clans/ PMID- 17344240 TI - Codelink: an R package for analysis of GE healthcare gene expression bioarrays. AB - MOTIVATION: Microarray-based expression profiles have become a standard methodology in any high-throughput analysis. Several commercial platforms are available, each with its strengths and weaknesses. The R platform for statistical analysis and graphics is a powerful environment for the analysis of microarray data, because it has many integrated statistical methods available as well as the specialized microarray analysis project Bioconductor. Many packages have been added in the last few years increasing the range of possible analysis. Here, we report the availability of a package for reading and analyzing data from GE Healthcare Gene Expression Bioarrays within the R environment. AVAILABILITY: The software is implemented in the R language, is open source and available for download free of charge through the Bioconductor (http://www.bioconductor.org) project. PMID- 17344241 TI - pcaMethods--a bioconductor package providing PCA methods for incomplete data. AB - pcaMethods is a Bioconductor compliant library for computing principal component analysis (PCA) on incomplete data sets. The results can be analyzed directly or used to estimate missing values to enable the use of missing value sensitive statistical methods. The package was mainly developed with microarray and metabolite data sets in mind, but can be applied to any other incomplete data set as well. AVAILABILITY: http://www.bioconductor.org PMID- 17344242 TI - From structure to dynamics of metabolic pathways: application to the plant mitochondrial TCA cycle. AB - MOTIVATION: Mitochondrial metabolism, dominated by the reactions of the tricarboxylic acid (TCA) cycle, is of vital importance for a wide range of metabolic processes. In particular for autotrophic tissue, such as plant leaves, the TCA cycle marks the point of divergence of anabolic pathways and plays an essential role in biosynthesis. However, despite extensive knowledge about its stoichiometric properties, the function and the dynamical capabilities of the TCA cycle remain largely unknown. METHODS AND RESULTS: Based on a recently proposed formalism, we investigate the dynamic and functional properties of the mitochondrial TCA cycle of plants. Starting with the structural properties, as described by the elementary flux modes of the system, we aim for the transition from structure to the dynamics of the TCA cycle. Using a parametric description of the system, encompassing all possible differential equations and parameter values, we detect and quantify regimes of different dynamic behavior. Optimizing the system with respect to dynamic stability, we demonstrate that maximal stability is associated with specific (relative) metabolite concentrations and flux values that are subsequently compared to the experimental literature. Our analysis also serves as a general example how to elucidate the transition from the structure to the dynamics of metabolic pathways. PMID- 17344243 TI - MedicCyc: a biochemical pathway database for Medicago truncatula. AB - MOTIVATION: There is an imperative need to integrate functional genomics data to obtain a more comprehensive systems-biology view of the results. We believe that this is best achieved through the visualization of data within the biological context of metabolic pathways. Accordingly, metabolic pathway reconstruction was used to predict the metabolic composition for Medicago truncatula and these pathways were engineered to enable the correlated visualization of integrated functional genomics data. RESULTS: Metabolic pathway reconstruction was used to generate a pathway database for M. truncatula (MedicCyc), which currently features more than 250 pathways with related genes, enzymes and metabolites. MedicCyc was assembled from more than 225,000 M. truncatula ESTs (MtGI Release 8.0) and available genomic sequences using the Pathway Tools software and the MetaCyc database. The predicted pathways in MedicCyc were verified through comparison with other plant databases such as AraCyc and RiceCyc. The comparison with other plant databases provided crucial information concerning enzymes still missing from the ongoing, but currently incomplete M. truncatula genome sequencing project. MedicCyc was further manually curated to remove non-plant pathways, and Medicago-specific pathways including isoflavonoid, lignin and triterpene saponin biosynthesis were modified or added based upon available literature and in-house expertise. Additional metabolites identified in metabolic profiling experiments were also used for pathway predictions. Once the metabolic reconstruction was completed, MedicCyc was engineered to visualize M. truncatula functional genomics datasets within the biological context of metabolic pathways. AVAILABILITY: freely accessible at http://www.noble.org/MedicCyc/ PMID- 17344244 TI - Intravenous immunoglobulins improve the function and ameliorate joint involvement in systemic sclerosis: a pilot study. AB - BACKGROUND: In systemic sclerosis (SSc), joint involvement may reduce the functional capacity of the hands. Intravenous immunoglobulins have previously been shown to benefit patients with SSc. AIM: To verify the efficacy of intravenous immunoglobulins on joint involvement and function in SSc. PATIENTS AND METHODS: 7 women with SSc, 5 with limited and 2 with diffuse SSc, with a severe and refractory joint involvement were enrolled in the study. Methotrexate and cyclophosphamide pulse therapy did not ameliorate joint symptoms. Hence, intravenous immunoglobulins therapy was prescribed at a dosage of 2 g/kg body weight during 4 days/month for six consecutive courses. The presence of joint tenderness and swelling, and articular deformities (due to primary joint involvement and not due to skin and subcutaneous changes) were evaluated. Before and after 6 months of treatment, patients were subjected to (1) Ritchie Index (RI) evaluation of joint involvement; (2) Dreiser Algo-Functional Index (IAFD) evaluation of hand joint function; (3) pain visual analogue scale (VAS) to measure joint pain; (4) Health Assessment Questionnaire (HAQ) to evaluate the limitations in everyday living and physical disability; and (5) modified Rodnan Skin Score for skin involvement. RESULTS: After 6 months of intravenous immunoglobulins therapy, joint pain and tenderness, measured with the VAS, decreased significantly (p<0.03), and hand function (IAFD) improved significantly (p<0.02), together with the quality of life (HAQ; p<0.03). All patients significantly improved, except for one. The skin score after 6 months of intravenous immunoglobulins therapy was significantly reduced (p<0.003). CONCLUSION: This pilot study suggests that intravenous immunoglobulins may reduce joint pain and tenderness, with a significant recovery of joint function in patients with SSc with severe and refractory joint involvement. The cost of intravenous immunoglobulins might limit their use only to patients who failed disease-modifying antirheumatic drugs. PMID- 17344245 TI - Genetic variations of Toll-like receptor 9 predispose to systemic lupus erythematosus in Japanese population. AB - BACKGROUND: Systemic lupus erythematosus (SLE) is characterised by dysregulation of autoreactive lymphocytes and antigen-presenting cells. Signalling through Toll like receptor 9 (TLR9), a mediator of innate immune responses, has a role in activation of dendritic cells and autoreactive B cells. OBJECTIVE: To investigate whether TLR9 polymorphisms are associated with an increased risk of SLE. METHODS: DNA samples were obtained from 220 Japanese patients with SLE (with >4 American College of Rheumatology criteria for SLE) and 203 controls. The genetic variations of TLR9 were detected by PCR, followed by DNA sequencing. The promoter and enhancer activities of TLR9 were measured by luciferase reporter gene assay. The titres of anti-dsDNA antibodies in sera from control or TLR9-deficient mice were analysed by ELISA. RESULTS: The G allele at position +1174 (located in intron 1 of TLR9) is closely associated with an increased risk of SLE (p = 0.029). Furthermore, patients with SLE tend to have C allele at position -1486 (p = 0.11). Both alleles down regulate TLR9 expression by reporter gene assay. TLR9 deficient mice under a C57BL/6 background possess higher titres of anti-dsDNA serum antibodies than control C57BL/6 mice. CONCLUSIONS: These results indicate that the presence of the G allele at position +1174 of TLR9 predisposes humans to an increased risk of SLE. It is speculated that TLR9 normally prevents the development of human SLE. PMID- 17344247 TI - What can be gained from comprehensive disaggregate surveillance? The Avon Surveillance System for Sexually Transmitted Infections. AB - OBJECTIVE: To describe a new disaggregate surveillance system covering key diagnosed sexually transmitted infections in a UK locality. METHODS: The Avon System for Surveillance of Sexually Transmitted Infections (ASSIST) collects computerised person- and episode-based information about laboratory-diagnosed sexually transmitted infections from genitourinary medicine (GUM) clinics, the Avon Brook Clinic, and the Health Protection Agency and trust laboratories in primary care trusts in Avon. The features of the system are illustrated here, by describing chlamydia-testing patterns according to the source of test, age and sex, and by mapping the distribution of chlamydia across Bristol, UK. RESULTS: Between 2000 and 2004, there were 821,685 records of tests for sexually transmitted infections, with 23,542 positive results. The proportion of tests and positive results for chlamydia and gonorrhoea sent from general practice increased over time. Most chlamydia tests in both GUM and non-specialist settings were performed on women aged >25 years, but positivity rates were highest in women aged <25 years. The positivity rate remained stable between 2000 and 2004. Including data from all diagnostic settings, chlamydia rates were about twice as high as those estimated only from genitourinary clinic cases. CONCLUSIONS: The ASSIST model could be a promising new tool for planning and measuring sexual health services in England if it can become sustainable and provide more timely data using fewer resources. Collecting denominator data and including infections diagnosed in primary care are essential for meaningful surveillance. PMID- 17344246 TI - Non-steroidal anti-inflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials. AB - OBJECTIVE: The comparative risk of myocardial infarction (MI) with cyclo oxygenase-2-specific drugs and traditional non-steroidal anti-inflammatory drugs (NSAIDs) was determined. METHODS: The results of studies of a suitable size in colonic adenoma and arthritis-that had been published in English and from which crude data about MIs could be extracted-were evaluated. Medline, Embase and Cinahl (2000-2006) databases, as well as published bibliographies, were used as data sources. Systematic reviews examined MI risks in case-control and cohort studies, as well as in randomised controlled trials (RCTs). RESULTS: 14 case control studies (74 673 MI patients, 368 968 controls) showed no significant association of NSAIDs with MI in a random-effects model (OR 1.17; 95% CI 0.99 to 1.37) and a small risk of MI in a fixed-effects model (OR 1.32; 95% CI 1.29 to 1.35). Sensitivity analyses showed higher risks of MI in large European studies involving matched controls. Six cohort studies (387 983 patient years, 1 120 812 control years) showed no significant risk of MI with NSAIDs (RR 1.03; 95% CI 1.00 to 1.07); the risk was higher with rofecoxib (RR 1.25; 95% CI 1.17 to 1.34) but not with any other NSAIDs. Four RCTs of NSAIDs in colonic adenoma (6000 patients) showed an increased risk of MI (RR 2.68; 95% CI 1.43 to 5.01). Fourteen RCTs in arthritis (45 425 patients) showed more MIs with cyclo-oxygenase-2-specific drugs (Peto OR 1.6; 95% CI 1.1 to 2.4), but fewer serious upper gastrointestinal events (Peto OR 0.40; 95% CI 0.31 to 0.53). CONCLUSION: The overall risk of MI with NSAIDs and cyclo-oxygenase-2-specific drugs was small; rofecoxib showed the highest risk. There was an increased MI risk with cyclo-oxygenase-2-specific drugs compared with NSAIDs, but less serious upper gastrointestinal toxicity. PMID- 17344248 TI - "But there are no snakes in the wood": risk mapping as an outcome measure in evaluating complex interventions. AB - OBJECTIVES: To complement biological and social behavioural markers in evaluating the complex intervention of sexual and reproductive health among adolescents in rural Zimbabwe, community-derived markers of effectiveness were sought. Through a participatory workshop with adolescent boys and girls, an innovative "risk map research workshop" was developed to be conducted throughout the study sites. METHODS: 78 gender-specific standardised workshops were conducted among secondary school students. Participants drew risk maps of their community. Focus group discussions explored each risk area identified on the map. Grounded Theory was used to create "categories" and "subcategories." Workshops continued to be held until "saturation", whereby no new categories emerged. "Axial coding" identified the inter-relationship between categories and subcategories according to their relevance to sexual and reproductive health risk. RESULTS: Six "risk area" Grounded Theory categories emerged from the data: bush/rural terrain, commercial centres, homes, school environs, religious and spiritual venues, and roadsides. 17 subcategories emerged, grouped under each of the risk area categories, such as riverbeds, growth points, homesteads, classrooms, all-night prayer meetings and truck stops. Risks and the consequences of risks included sexually transmitted infections (including HIV), violence, sexual abuse, expulsion from school and illegal abortion. CONCLUSIONS: Risk maps provide unique data that can be used to measure more subtle changes that occur as a result of social behavioural interventions aimed at addressing reproductive and sexual health. Another round of risk map research workshops will be held towards the end of the study to explore changes in milieu, behaviour and experiences, and will complement and triangulate the biological and other social behavioural outcome measures. PMID- 17344249 TI - Pregnancy outcomes in women infected with Chlamydia trachomatis: a population based cohort study in Washington State. AB - OBJECTIVES: To measure the risk of preterm delivery, premature rupture of membranes, infant low birth weight and infant mortality, by a population-based retrospective cohort study using Washington State birth certificate data. METHODS: All women diagnosed with Chlamydia trachomatis infection (n = 851), noted with a check box on the birth certificate from 2003, and a randomly selected sample of women not diagnosed with C trachomatis (n = 3404) were identified. To assess the RR between chlamydia infection and pregnancy outcomes, multivariable logistic regression analysis was used. RESULTS: Women with chlamydia infection were younger, more likely to be non-white and had less years of education compared with women without chlamydia. Additionally, they were more likely to have inadequate prenatal care and coinfections with other sexually transmitted infections. After adjusting for age and education, chlamydia-infected women were at an increased risk of preterm delivery (RR 1.46, 95% CI 1.08 to 1.99) and premature rupture of membranes (RR 1.50, 95% CI 1.03 to 2.17) compared with non-infected women. However, no increased risk of infant death (RR 1.02, 95% CI 0.37 to 2.80) or low birth weight (RR 1.12, 95% CI 0.74 to 1.68) associated with chlamydia infection was observed. CONCLUSION: This study suggests that C trachomatis is associated with an increased risk of preterm delivery and premature rupture of membranes, but not with infant death and low birth weight. Routine screening and opportune treatment for C trachomatis should be considered a necessary part of prenatal care to reduce these adverse pregnancy outcomes. PMID- 17344250 TI - Inequalities in provision of the Disability Living Allowance for Down syndrome. AB - OBJECTIVES: To assess factors associated with granting of the Disability Living Allowance (DLA) for Down syndrome. DESIGN: Cross-sectional survey. SETTING: Families with a child with Down syndrome enrolled in a community-based trial of vitamin supplementation. PARTICIPANTS: 156 children with trisomy 21 (59% male, 20% non-white) were enrolled before 7 months of age and 138 completed follow-up. MAIN OUTCOME MEASURES: Before the child was 2 years old, we surveyed parents about applications for the DLA and socioeconomic factors, and assessed the child's development. RESULTS: Application for the DLA was not associated with ethnicity or speaking English. Significantly fewer ethnic minority parents (OR = 0.10; 95% CI 0.03 to 0.35; 69% vs 96%, risk difference 27%) and parents with English as a second language (OR = 0.15: 95% CI 0.04 to 0.62; 67% vs 93%, risk difference 26%) were granted the DLA. Amongst those granted the DLA, ethnic minority families were significantly less likely to be granted a higher monetary award (OR = 0.19; 95% CI 0.06 to 0.55). Severity of disability, reflected by quartile of Griffiths Developmental Quotient or the presence of severe cardiac disease requiring surgery, was not associated with application, granting or level of the DLA award. CONCLUSIONS: Although all children with Down syndrome meet some of the criteria for the DLA, only 80% were receiving this benefit. The decision to award the DLA and the monetary level of the award favoured white, English speaking parents and was not related to severity of disability. Routine monitoring of awards by ethnicity and language spoken is needed. TRIAL REGISTRATION NUMBER: NCT00378456. PMID- 17344251 TI - Randomised controlled trial of nasal continuous positive airways pressure (CPAP) in bronchiolitis. AB - AIMS: To compare continuous positive airways pressure (CPAP) with standard treatment (ST) in the management of bronchiolitis. METHODS: Children <1 year of age with bronchiolitis and capillary PCO2 >6 kPa were recruited and randomised to CPAP or ST and then crossed over to the alternative treatment after 12 h. ST was intravenous fluids and supplemental oxygen by nasal prongs or face mask. The change in PCO2 was compared between the groups after 12 and 24 h. Secondary outcomes were change in capillary pH, respiratory rate, pulse rate and the need for invasive ventilatory support. RESULTS: 29 of 31 children completed the study. PCO2 after 12 h fell by 0.92 kPa in children treated with CPAP compared with a rise of 0.04 kPa in those on ST (p<0.015). If CPAP was used first, there was a significantly better reduction in PCO2 than if it was used second. There were no differences in secondary outcome measures. CPAP was well tolerated with no complications identified. CONCLUSIONS: This study suggests that CPAP compared with ST improves ventilation in children with bronchiolitis and hypercapnoea. PMID- 17344252 TI - Posture and movement in healthy preterm infants in supine position in and outside the nest. AB - OBJECTIVE: To evaluate whether lying in a nest affects the posture and spontaneous movements of healthy preterm infants. METHOD: 10 healthy preterm infants underwent serial video recording in the supine position, when lying in a nest and outside it, at three ages: 30-33 weeks postmenstrual age (PMA) (early preterm), 34-36 weeks PMA (late preterm) and 37-40 weeks PMA (term). The nest was shell-shaped, made by putting two rolled blankets in a form of an oval. Posture was assessed both before and after general movements by scoring the predominant postural pattern. Movements towards and across the midline, elegant wrist movements, abrupt hand and/or limb movements, rolling to side, and frozen postures of the arms and legs were assessed during four general movements. All data relating to motor and postural items were normalised into frequencies of events per minute because the general movements varied in duration. RESULTS: When lying in the nest, the infants more often displayed a flexed posture with shoulder adduction and elbow, and hip and knee flexion, and the head was frequently in the midline. The nest was also associated with an increase in elegant wrist movements and movements towards and across the midline and a reduction in abrupt movements and frozen postures of the limbs. The nest did not affect the occurrence of asymmetrical tonic neck posture. CONCLUSIONS: A nest promotes a flexed posture of the limbs with adduction of shoulders, facilitates elegant wrist movements and movements towards and across the midline and reduces abrupt movements and frozen postures of the arms and legs. PMID- 17344253 TI - Accuracy of pulse oximetry in screening for congenital heart disease in asymptomatic newborns: a systematic review. AB - OBJECTIVE: To evaluate the accuracy of pulse oximetry as a screening tool for congenital heart disease in asymptomatic newborns. DESIGN, DATA SOURCES AND METHODS: Systematic review of relevant studies identified through MEDLINE, EMBASE, Cochrane Library, MEDION, and bibliographies of retrieved primary and review articles. Two reviewers independently extracted data on study characteristics, quality and results to construct 2x2 tables with congenital heart disease as the reference standard. A random-effects bivariate model was used to meta-analyse estimates of sensitivity and specificity. Logit pairs of sensitivity and specificity of each study were analysed in a single model, accounting for their correlation due to differences in threshold between studies. RESULTS: Eight studies were included with a total of 35 960 newborns. Pulse oximetry was performed on asymptomatic newborns in all studies; three studies excluding newborns with an antenatal diagnosis of congenital heart disease. Either functional or fractional oxygen saturation was measured by pulse oximetry with oxygen saturation below 95% as the cut-off level in most studies. On the basis of the eight studies, the summary estimates of sensitivity and specificity were 63% (95% CI 39% to 83%) and 99.8% (95% CI 99% to 100%), respectively, yielding a false positive rate of 0.2% (95% CI 0% to 1%). CONCLUSION: Pulse oximetry was found to be highly specific tool with very low false positive rates to detect congenital heart disease. Large, well-conducted prospective studies are needed to assess its sensitivity with higher precision. PMID- 17344254 TI - Lethal opioids or dangerous prescribers? PMID- 17344255 TI - Respiratory function during parenteral opioid titration for cancer pain. AB - BACKGROUND: Respiratory depression is the most feared opioid-related side-effect yet research on the topic is sparse. We evaluated changes in respiratory parameters during parenteral opioid titration for cancer pain to determine if opioid titration was associated with evidence of hypoventilation. The primary outcome measure was to measure changes in end-tidal CO(2) (ET-CO(2)) during opioid titration to pain control. METHODS: Subjects with severe cancer pain admitted for parenteral opioid titration for poorly controlled pain were eligible. Those who were oxygen dependent were excluded. ET-CO(2), O(2) saturation, respiratory rate (RR), and vital signs were monitored daily until pain control was achieved. RESULTS: 30 patients completed the study of which 29 are reported. The mean ET-CO(2) at initial evaluation was 33.39 -/+ 5.0 and 34.79 -/+ 5.7 mmHg at pain control (P =0.14, 95% CI -0.5 to 3.3). None had an ET-CO(2) > or =50 mmHg. All maintained O(2) saturation > or = 92%. RR dropped transiently below 10/minute in two subjects. CONCLUSIONS: Parenteral opioid titration for relief of cancer pain was not associated with respiratory depression as demonstrated by significant changes in ET-CO(2) or oxygen saturation in non oxygen dependent cancer patients. PMID- 17344256 TI - The value of cognitive interviewing techniques in palliative care research. AB - BACKGROUND: In answering questionnaires, research participants undertake complex cognitive processes, including understanding/interpreting questions, retrieval of information from memory, decision processes to estimate answers and response formulation. Cognitive interviewing techniques are widely used in large surveys, to improve questionnaires by understanding these processes, but their use is less familiar in other areas of palliative research. AIM: This study applied cognitive interviewing techniques, alongside standard piloting, to refine a questionnaire for survey of symptoms in end-stage renal disease patients. METHODS: Ten consecutive renal patients were invited to undertake a cognitive interview, while completing a questionnaire comprised of the Memorial Symptom Assessment, Geriatric Depression and Palliative Care Outcomes Scales. Interviews were conducted using 'think-aloud' and concurrent probing techniques, and recorded, transcribed and analysed using content analysis. RESULTS: Nine interviews were completed. A variety of cognitive problems were identified, including legibility/format, comprehension of specific words/phrases, inapplicability of some questions, response estimation and difficulties caused by combining instruments. These were categorized, using Tourangeau's information processing model, and used to refine the symptom questionnaire. CONCLUSION: Cognitive interviewing was able to helpfully identify the range and depth of difficulties with questions, to a greater degree than with standard piloting. It may be of particular benefit when instruments are used in different combinations, or applied to new study populations. Wider use of these techniques in palliative research is recommended. PMID- 17344258 TI - Loss and change: experiences of people severely affected by multiple sclerosis. AB - This study aimed to explore important issues for people severely affected by multiple sclerosis (MS). Individual interviews were conducted with 23 people with MS (PwMS) and 17 informal carers, the data relating to 32 PwMS. Information was obtained about 19 females and 13 males, with a mean age of 55, median time from diagnosis was 14.5 years, and physical disabilities ranged from mild to severe, although fifteen patients had severe disabilities. Twenty-six of the 32 individuals were unable to walk, 24 were catheterised, and 18 had considerably impaired or no upper limb function. Personal issues in relation to loss and change, particularly in terms of losses of or changes in physical abilities, including maintaining mobility, independence, relationships and social role were raised commonly in response to an open-ended question about what issues were important in living with MS. Coping with MS requires individuals to deal with the losses and changes brought about by their illness. Our study suggests that even patients who have had MS for many years and are now severely affected continue to experience loss and change. We recommend that attention be given to emotional support which specifically addresses three main areas of dealing with loss and change for people that are severely affected--physical issues, independence and relationships. Palliative care providers may have expertise in managing loss that could be useful for these patients in partnership with neurological services. PMID- 17344257 TI - Dying trajectories in heart failure. AB - OBJECTIVES: To explore dying trajectories in heart failure. DESIGN: Prospective, longitudinal study. SETTING: Sixteen GP surgeries in four demographically contrasting areas of the UK. PARTICIPANTS: A total of 27 heart failure patients, >60 years of age, who completed questionnaires for at least five time-points before death. MAIN OUTCOME MEASURES: Kansas City Cardiomyopathy Questionnaire Physical Limitation Scale. RESULTS: No 'typical' dying trajectory could be identified, and only a minority of patients conformed to the theoretical trajectory of dying in heart failure. CONCLUSIONS: This study provides the first prospective data regarding physical decline prior to death in heart failure. Findings challenge current efforts to plan and deliver palliative care services on the basis of the theoretical heart failure dying trajectory. PMID- 17344259 TI - Palliative care in patients with severe multiple sclerosis: two case reports and a survey among German MS neurologists. AB - Due to its chronic and fluctuating time course, multiple sclerosis (MS), thus far, has not been regarded as a focus of palliative care. However, sometimes we are confronted with severely affected MS patients, who suffer from complex medical, physical and psychosocial problems, which are not fully covered by the current health care services. We present two cases of severely affected MS patients we saw in our outpatient MS clinic, and who, we believe, are candidates for palliative care. The first patient, with primary chronic progressive (pcP) MS for many years (Expanded Disability Status Scale (EDSS): 8.0) presented with complex painful dysaesthesias and a depressive syndrome. He refused any treatment, and finally committed suicide with the help of a euthanasia group in Switzerland. The second patient was also severely affected by a secondary chronic progressive (scP) MS (EDSS: 9.0) and was finally admitted to our palliative care unit due to a complex pain syndrome associated with panic attacks and anxiety. She spent three weeks on the palliative care unit and her symptoms improved gradually after changing and optimising her pain medication. The patient was discharged with home care and is seen regularly on the palliative care unit. Additionally, as a first step, a questionnaire was sent to 53 German MS specialists regarding their general view on the needs for palliative care in MS. Our two cases and the results of the questionnaire demonstrated that MS patients and their caregivers are confronted with a variety of symptoms which are difficult to treat, and are a cause of great suffering for the patients, including ataxia, depression and fatigue. The data of the questionnaire also showed that neurologists usually do not deal with end-of-life care issues in MS.More research is needed to define the role of palliative care in MS and establish appropriate interventions to improve the quality of life in advanced stage MS patients and their relatives. PMID- 17344260 TI - Feeling like a burden to others: a systematic review focusing on the end of life. AB - Research into the burden of illness has focused predominantly on family caregivers, with little consideration of the other side of the caregiving relationship-care recipients' perspectives on having become a 'burden to others'. However, there is now a small but growing body of evidence to suggest that worry about creating burden to others is a common and troubling concern for people who are nearing the end of their lives. This concern is referred to as 'self perceived burden'. The present study provides a systematic review of the literature, addressing self-perceived burden at the end of life. Using standard methods, literature was searched for relevant studies in palliative care and related fields. The review revealed that self-perceived burden is reported as a significant problem by 19- 65% of terminally ill patients. It is correlated with loss of dignity, suffering, and a 'bad death'. Self-perceived burden has also been identified as a relevant factor in death-hastening acts among patients with life-threatening illness, as well as in clinical decisions, such as the choice of place of care at the end of life, advance directives, and acceptance of treatment. Given the unique challenges faced by patients with advanced disease and their families, there is a need for further investigation into this under researched area. PMID- 17344261 TI - Fighting a losing battle: eating-related distress of men with advanced cancer and their female partners. A mixed-methods study. AB - BACKGROUND: Anorexia/cachexia is a frequent complication of advanced cancer with poorly understood psychosocial impact or eating-related distress (ERD) on both patients and family members. To assist palliative care practitioners manage this important psychosocial aspect of care, we aimed to discover and describe elements of ERD, focusing on male patients with advanced cancer and their female partners. METHODS: Nineteen male patients and their partners were systematically investigated by (1) focus group interviews and data analysis inspired by Grounded Theory, and (2) a comparative survey with categorical questions. RESULTS: For patients, eating-related distress was characterised by obstruction to eating, poor and capricious appetite, a disconnection of oral intake and ability to gain weight, and continuous efforts to eat. Partners expressed feelings of deep concern, frustration, and insufficiency in their loving and innovative efforts to prepare appealing food. Partners were more concerned about patients' weight loss than patients themselves (P =0.002). Patients felt more pressure to eat from partners than they estimated (P =0.007). CONCLUSION: Anorexia/cachexia of male cancer patients affects the cooking at home, a couple's daily eating routines, and their spousal relationship. Identification of ERD may trigger targeted psychosocial interventions. PMID- 17344262 TI - Views of oncology patients, their relatives and oncologists on cardiopulmonary resuscitation (CPR): questionnaire-based study. AB - BACKGROUND: Doctors are justified withholding a treatment, such as cardiopulmonary resuscitation (CPR), if it is unlikely to benefit a patient. The success rates for CPR in patients with cancer is <1%. Guidelines produced in 2001 recommended that CPR should be discussed with patients, even when it is unlikely to be successful. Therefore, should oncologists always discuss resuscitation, even when it is likely to be futile? METHOD: Sixty oncology in-patients and 32 of their relatives were asked their views on CPR, and their views were compared with the oncologist involved in their care. RESULTS: Some 58% of patients wanted to be resuscitated. There was a moderate-strong correlation between patients and their next of kin and the desire for resuscitation. There was also a positive correlation between the doctor's views on suitability for resuscitation, patient's prognostic score, and World Health Organisation (WHO) performance score. CONCLUSION: Most patients wanted to be resuscitated despite being given the likely poor survival rates from CPR. They also wanted to be involved in the decision-making process, and wanted their next of kin involved, even when, medically, the procedure was unlikely to be successful. The findings that patient and next of kin views correlated well shows that relatives' views are a good representation of patient views. In contrast, consultant's decisions were strongly correlated with the patient's performance status and clinical state. No patients were upset by the study, although nine patients declined to participate. PMID- 17344263 TI - Demographic factors and awareness of palliative care and related services. AB - BACKGROUND: Palliative care is not accessed by all those who can benefit from it. Survey aim: To explore awareness of palliative care and related services among UK oncology out-patients, and to analyse the relationship between demographic characteristics and knowledge. DESIGN: Cross-sectional interview-based survey. Analysis comprised univariate and multiple logistic regression. PARTICIPANTS AND SETTINGS: Oncology out-patients receiving curative treatments at two district general hospitals in north-west London between December 2004 and April 2005. RESULTS: A total of 252 (94%) eligible clinic patients were interviewed. Only 47 (18.7%) patients recognised the term 'palliative care', but 135 (67.8%) understood the role of the hospice, and 164 (66.7%) understood the role of Macmillan nurses. Age-adjusted multiple logistic regression showed that recognizing the term 'palliative care' was more likely among the most socially and materially affluent patients than those who were the poorest (OR: 8.4, CI: 2.17-31.01, p =0.002). Understanding the role of Macmillan nurses was also more likely among the most socially and materially affluent patients compared with the poorest patients (OR: 7.0, CI: 2.41-18.52, p <0.0001), and was independently less likely among patients from black and minority ethnic groups than those who were classified as being white British (OR=0.5, CI:0.25-0.96, p =0.04). CONCLUSIONS: Awareness of palliative care and related services was low among black and minority ethnic groups, and the least affluent. PMID- 17344264 TI - Undergraduate training in palliative medicine in Germany: what effect does a curriculum without compulsory palliative care have on medical students' knowledge, skills and attitudes? AB - INTRODUCTION: The effect of a curriculum without compulsory courses in palliative medicine on students' knowledge, kills and attitudes towards the care of dying patients and decisions at the end of life was investigated. METHODS: In a cross sectional, questionnaire based survey at the medical school of Bonn 1st, 3rd and 5th year students had to grade their knowledge and skills in items concerning palliative medicine. Attitudes towards end of life decisions were queried. RESULTS: The return rate was 78%. Significant increase in self estimation of certainty comparing 1st to 5th year students were detected for the items distinction between palliative and curative medicine (p <0.001), symptom control (p <0.001), pain management (p =0.001) and communication (p =0.036). No significant differences were recorded for the items accompaniment of dying patients, breaking bad news and integration of spiritual aspects. The low overall certainty is reflected in poor knowledge. A significant decrease of the approval for euthanasia by request was evident (p =0.012). DISCUSSION: A medical curriculum without compulsory course does increase confidence in some of the core competencies in palliative care, but the overall results at the end of the training are poor. The WHO claims that palliative care has to be "compulsory in courses leading to a basic professional qualification" has still to be fulfilled in Germany. This study can serve as a baseline to evaluate the effect of mandatory courses in palliative care. PMID- 17344265 TI - Symptom scores, serotonin and 5-hydroxyindole acetic acid levels in cancer patients with and without bowel obstruction. PMID- 17344268 TI - Eliot Freidson's revolution in medical sociology. PMID- 17344269 TI - The bioethics of medical research in very poor countries. AB - Sociologists have had only a marginal effect on the development of bioethical principles for medical research despite their interest in the effects of social and economic inequality on health and its implications for issues of social and individual justice. In this article we review existing bioethical standards for conducting medical research in very poor countries. Given the substantial differences in individual exposure to health risks and the availability of health protective resources as well as differences in the disease burden and mortality and morbidity at the population level, it is clear that illness in poor countries can be better understood using a social causation of illness perspective. In turn we suggest that such a perspective can be useful for identifying bioethical standards that better apply in this context. PMID- 17344270 TI - Maintaining face in the presentation of depression: constraining the therapeutic potential of the consultation. AB - This article discusses the concerns of patients diagnosed with depression to preserve 'face' in social and medical encounters. The findings are from a qualitative study of patient and GP accounts of the presentation, recognition and treatment of depression. Medical consultations are difficult encounters to accomplish successfully, especially for patients, who often strive to protect their privacy and personal integrity through the maintenance of face. Face work reveals the concern of participants to contribute to the success of the consultation as a social interaction. Patients' strategy of maintaining face helps to account for the commonly reported underdetection of psychosocial distress in general practice consultations. Many people do not regard the experience of psychosocial distress as an appropriate topic for medical consultation or scrutiny. In this case, face work can function as a means of maintaining privacy and resisting medical diagnosis and intervention. The concept of face has relevance in other areas of clinical care, including chronic and enduring pain, functional disorders, medically unexplained symptoms and even terminal illness. Consideration of face work reveals the extent to which the pressure to contribute to the success of the consultation as a social encounter may constrain participants' capacity to realize its therapeutic potential. The extent to which clinical interactions are governed by social etiquette also helps to explain the continuing inertia of the formal health care system and the difficulty of changing the ways that patients and doctors communicate with each other, and of increasing patients' involvement in medical consultations. PMID- 17344271 TI - Prescribing benzodiazepines in general practice: a new view of an old problem. AB - General practitioner (GP) prescribing has been identified as an arena that has broad social and political implications, which stretch beyond individual outcomes for patients. This article revisits aspects of the controversy about prescribing benzodiazepines (or 'minor tranquillizers') through an exploration of contemporary views of GPs. In the 1980s the prescribing of these drugs was considered to be both a clinical and social problem, which brought medical decision making under public scrutiny. The legacy of this controversy for recent GPs remains a relatively under-explored topic. This article describes a qualitative study of GPs practising in the north-west of England about their views of prescribing benzodiazepines. The accounts of the respondents highlight a number of points about: blame allocation, past and present; clinical challenges about risk management; and deserving and undeserving patients. These GP views are then discussed in the wider context of psychotropic drug use. It is concluded that, while there has been a recent consensus that the benzodiazepines have been problematic, when they are placed in a longer historical context, a different picture is apparent because other psychotropic drugs have raised similar problems. PMID- 17344272 TI - Does money buy better health? Unpacking the income to health association after midlife. AB - This article estimates the effect of household financial resources on health after midlife using models that minimize health-related selectivity and unobserved heterogeneity bias. I focus on the self-rated health and mobility limitations of adults transitioning into retirement over six panels of the Health and Retirement Study (1992-2002; age 51-61 at wave one; N = 7602). Standard regression models that adjust for health-related selection with prospective and retrospective controls suggest a significant influence of long-term income on health, but an insignificant influence of short-term income. Further adjustment for unobserved fixed effects also suggests that short-term income is insignificant. Sizable recent and long-term health feedbacks to income for a portion of the HRS respondents underscore the need to control for the confounding influence of health over the lifecourse. Together these results suggest that adults after midlife are heterogeneous with respect to the causal and selective processes generating the observed association between income and health. PMID- 17344273 TI - lIlness as argumentation: a prolegomenon to the rhetorical study of contestable complaints. AB - The resources of rhetorical theory, the classical theory of persuasion, can be marshaled to help physicians evaluate patient complaints for which there is no corresponding objective evidence and which rely, therefore, on the persuasiveness of patients to be taken seriously (contestable complaints). An appropriate focus for the evaluation of such complaints is argumentation itself: what, in the absence of objective evidence of disease, counts as a good argument for a patient to be eligible for medical attention? How do patients convince physicians that they are ill and in need of care - and, conversely, how do physicians convince patients, when the need arises, that they are well and not good candidates for medical intervention? Two rhetorical concepts are especially productive for the analysis of argumentation. One is kairos, the Sophistic notion of contingency, and the other is pisteis, the Aristotelian catalogue of persuasive appeals. A focus on types of arguments directs attention away from types of patients (difficult, suspect, malingering and so on), and provides a more neutral means of judging claims to illness. PMID- 17344274 TI - Clinical life: expectation and the double edge of medical promise. AB - This article introduces the concept of clinical life to capture a form of life produced in the pursuit and wake of medically achieved longevity. Relying on the retrospective accounts of 28 individuals over age 70 who have undergone cardiac bypass surgery, angioplasty or a stent procedure, as well as interviews with their families and with clinicians, we examine three features of clinical life. First, patients do not distinguish between clinical possibility and clinical promise, and thus assume that life can and will be improved by medical intervention in late life. Rather than anticipating a range of potential treatment outcomes, patients therefore expect the best-case scenario: that medical procedures will reverse aging, disease and the march of time. Second, patients then assess the value of their post-procedure lives in accordance with that expectation. Norms regarding what life 'should be like' at particular ages are continually recalibrated to the horizon of what is clinically possible. And third, the price of living longer entails a double-edged relationship with the clinic--it generates opportunities for bodily restoration and increased self worth but also creates ambivalence about the value of life. This latter feature of clinical life is rarely publicly acknowledged in an environment that emphasizes medical promise. PMID- 17344276 TI - Infliximab and adalimumab-induced thrombocytopenia in a woman with colonic Crohn's disease. PMID- 17344277 TI - Excess mortality rates in a cohort of patients infected with the hepatitis C virus: a prospective study. AB - OBJECTIVE: We analysed the Trent Hepatitis C cohort to determine standardised mortality ratios in patients infected with hepatitis C virus (HCV), and to identify risk factors and associations with all-cause and liver-related mortality. DESIGN: Cohort study. SETTING: Patients with HCV infection attending secondary care within the Trent region of England. PATIENTS: 2285 patients with hepatitis C, followed for 1 year or more. MAIN OUTCOME MEASURES: The death rate in the cohort was compared to that seen in an age- and sex-matched English population. We performed Cox regression analyses to identify factors predictive of all-cause mortality and deaths from liver disease. RESULTS: Standardised mortality ratios in the cohort were three times higher than those expected in the general population of England. The excess deaths were due to liver-related causes and those associated with a drug-using lifestyle. Significant independent predictors of all-cause mortality were age, sex, treatment (protective) and liver biopsy fibrosis. Age, treatment, liver biopsy fibrosis and mean alcohol consumption were predictors of liver-related mortality. HCV was mentioned on 23% of death certificates overall, and on 52% of those of patients dying from a liver related cause. CONCLUSIONS: Our findings demonstrate that the death rate in patients infected with hepatitis C is three times higher than expected. Severity of disease is associated with a worse prognosis, whilst treatment improves outcome, particularly in those who respond. Use of death certificate data on HCV infection for planning purposes will result in considerable under-estimation of the HCV-related disease burden. PMID- 17344278 TI - Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. AB - BACKGROUND AND AIMS: During the long-term treatment of patients with hereditary haemochromatosis (HH) the authors observed that proton pump inhibitors (PPI) reduced the requirement for maintenance phlebotomy. Gastric acid plays a crucial role in non-haem iron absorption and the authors performed a case review and intervention study to investigate if PPI-induced suppression of gastric acid would reduce dietary iron absorption in C282Y homozygous patients. METHODS: Phlebotomy requirements to keep serum ferritin approximately 50 microg/l before (mean 6.1 (SE 0.6) years) and during (3.8 (0.9) years) administration of a PPI were evaluated in seven patients and a post-prandial study was performed to determine whether PPIs reduce absorption of non-haem iron (14.5 mg) from a test meal in a further 14 phlebotomised patients with normal iron stores. RESULTS: There was a significant reduction (p<0.001) in the volume of blood removed annually before (2.5 (0.25) l) and while taking (0.5 (0.25) l) a PPI. Administration of a PPI for 7d suppressed absorption of non-haem iron from the meal as shown by a significant reduction (all p<0.01) in: area under the serum curve (2145 (374) versus 1059 (219)), % recovery of administered iron at peak serum iron (20.5 (3.2) versus 11.0 (2.0)%) and peak serum iron (13.6 (2.4) vs 6.1 (1.2) micromol/l) (all values are before vs during PPI). CONCLUSIONS: Administration of a PPI to patients with HH can inhibit the absorption of non haem iron from a test meal and the habitual diet. PMID- 17344279 TI - HLA related genetic risk for coeliac disease. AB - BACKGROUND: Several studies have shown an elevated prevalence of coeliac disease (CD) in sibs of coeliac patients (risk 8-12%). AIM AND METHOD: We evaluated the risk that sibs of children with CD will also develop CD. This cohort of 188 Italian families was composed of probands with CD, at least one sib and both parents. CD status was determined and human leucocyte antigen (HLA)-DQ genotyping performed in all family members. The study also used a dataset of Italian triads (127 probands and both their parents) also genotyped for HLA-DQ. RESULTS: The overall risk that a sib of a CD patient will develop the disease was estimated at 10% in this sample. The risk estimate ranged from 0.1% to 29% when HLA-DQ information of the proband, parents and sib was considered. We found a negligible risk (lower than 1%) for 40% of the sibs of probands, a risk greater than 1% but less than 10% for 30%, and finally a high or very high risk (above 25%) in one third of families. CONCLUSION: These results make it possible to provide more accurate information to parents with a child with CD about the real risk for another child. An antenatal estimate of the order of risk of CD is now possible. Specific follow-up can thus be offered for babies at high risk. PMID- 17344280 TI - Amino acid 226 in the hemagglutinin of H9N2 influenza viruses determines cell tropism and replication in human airway epithelial cells. AB - Influenza A viruses of the H9N2 subtype are endemic in poultry in many Eurasian countries and have occasionally caused clinical respiratory diseases in humans. While some avian H9N2 viruses have glutamine (Q) at amino acid position 226 of the hemagglutinin (HA) receptor-binding site, an increasing number of isolates have leucine (L) at this position, which has been associated with the establishment of stable lineages of the H2 and H3 subtypes of viruses in humans. Little is known about the importance of this molecular trait in the infection of H9N2 viruses in humans. We show here that during the course of a single cycle of infection in human airway epithelial (HAE) cells cultured in vitro, the L-226 containing H9N2 viruses displayed human virus-like cell tropisms (preferentially infecting nonciliated cells) different from the tropisms showed by Q-226 containing H9N2 isolates (which infect both ciliated and nonciliated cells at ratios of 1:1 to 3:2) or other waterfowl viruses (which preferentially infect ciliated cells). During multiple cycles of replication in HAE cultures, L-226 containing H9N2 isolates grew consistently more efficiently and reached approximately 100-fold-higher peak titers than those containing Q-226, although peak titers were significantly lower than those induced by human H3N2 viruses. Our results suggest that the variation in residue 226 in the HA affects both cell tropism and replication of H9N2 viruses in HAE cells and may have implications for the abilities of these viruses to infect humans. PMID- 17344281 TI - Mitogen-activated protein kinases activate the nuclear localization sequence of human papillomavirus type 11 E1 DNA helicase to promote efficient nuclear import. AB - Human and animal papillomavirus DNA replicates as multicopy nuclear plasmids. Replication requires two viral proteins, the origin-recognition protein E2 and the replicative DNA helicase E1. Using genetic, biochemical, and immunofluorescence assays, we demonstrated that efficient nuclear import of the human papillomavirus (HPV) type 11 E1 protein depends on a codominant bipartite nuclear localization sequence (NLS) and on phosphorylation of the serine residues S89 and S93 by the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase, and c-Jun N-terminal protein kinase. The NLS and the MAPK substrates are located within a 50-amino-acid-long peptide near the amino terminus, previously designated the localization regulatory region (LRR). The downstream NLS overlaps the cyclin-binding motif RRL, which is necessary for phosphorylation by the cyclin-dependent kinases to inactivate a dominant nuclear export sequence, also in the LRR. Alanine mutations of the MAPK substrates significantly impaired nuclear import, whereas phospho-mimetic mutations partially restored nuclear import. We further identified two MAPK docking motifs near the C terminus of E1 that are conserved among E1 proteins of many HPVs and bovine papillomavirus type 1. Mutations of these MAPK docking motifs or addition of specific MAPK inhibitors significantly reduced nuclear import. Interestingly, a fraction of the NLS-minus E1 protein was cotransported with the E2 protein into the nucleus and supported transient viral DNA replication. In contrast, E1 proteins mutated in the MAPK docking motifs were completely inactive in transient replication, an indication that additional properties were adversely affected by those changes. PMID- 17344282 TI - The human cytomegalovirus virion possesses an activated casein kinase II that allows for the rapid phosphorylation of the inhibitor of NF-kappaB, IkappaBalpha. AB - We documented that the NF-kappaB signaling pathway was rapidly induced following human cytomegalovirus (HCMV) infection of human fibroblasts and that this induced NF-kappaB activity promoted efficient transactivation of the major immediate early promoter (MIEP). Previously, we showed that the major HCMV envelope glycoproteins, gB and gH, initiated this NF-kappaB signaling event. However, we also hypothesized that there were additional mechanisms utilized by the virus to rapidly upregulate NF-kappaB. In this light, we specifically hypothesized that the HCMV virion contained IkappaBalpha kinase activity, allowing for direct phosphorylation of IkappaBalpha following virion entry into infected cells. In vitro kinase assays performed on purified HCMV virion extract identified bona fide IkappaBalpha kinase activity in the virion. The enzyme responsible for this kinase activity was identified as casein kinase II (CKII), a cellular serine threonine protein kinase. CKII activity was necessary for efficient transactivation of the MIEP and IE gene expression. CKII is generally considered to be a constitutively active kinase. We suggest that this molecular characteristic of CKII represents the biologic rationale for the viral capture and utilization of this kinase early after infection. The packaging of CKII into the HCMV virion identifies that diverse molecular mechanisms are utilized by HCMV for rapid NF-kappaB activation. We propose that HCMV possesses multiple pathways to increase NF-kappaB activity to ensure that the correct temporal regulation of NF-kappaB occurs following infection and that sufficient threshold levels of NF kappaB are reached in the diverse array of cells, including monocytes and endothelial cells, infected in vivo. PMID- 17344283 TI - Role of the foamy virus Pol cleavage site in viral replication. AB - Foamy virus Pol precursor protein processing by the viral protease occurs at only one site, releasing a protease-reverse transcriptase and an integrase protein. To examine whether the cleavage of the Pol precursor protein is necessary for enzymatic activities and efficient viral replication, several mutations were generated around the cleavage site. All cleavage site mutants synthesize wild type levels of Pol precursor protein. Mutants containing more than two amino acid substitutions around the cleavage site exhibit no detectable Pol processing. The Pol cleavage site is not required for the production of infectious particles in a single round of infection, but is important for subsequent rounds of viral infection. Mutations around the cleavage site affected the enzymatic activities of the protease and reverse transcriptase and prevented replication after two rounds of infection. Interestingly, Pol encapsidation is significantly reduced in some of the mutants. PMID- 17344284 TI - Human cytomegalovirus downregulates expression of receptors for platelet-derived growth factor by smooth muscle cells. AB - Infection by human cytomegalovirus (HCMV) is associated with the development of vascular diseases and may cause severe brain damage in infected fetuses. Platelet derived growth factor receptors alpha and beta (PDGFR-alpha and -beta) control important cellular processes associated with atherosclerosis and fetal development. In the present investigation, our goal was to determine whether infection by HCMV can influence the expression of PDGFR-alpha and -beta in human smooth muscle cells (SMCs). In connection with HCMV infection in vitro the levels of PDGFR-alpha and -beta at the cell surface and in the total cellular protein of SMCs were reduced in parallel with decreases in the levels of the corresponding mRNAs. These effects were dependent on immediate-early (IE) or early (E) HCMV gene products, since inhibition of late genes did not prevent HCMV from affecting the expression of PDGFR-alpha and -beta. The downregulation of PDGFR caused by HCMV was dose dependent. Furthermore, confocal microscopy revealed that the localization of PDGFR-beta was altered in HCMV-infected cells, in which this protein colocalized with proteins associated with endosomes (Rab4 and -5) and lysosomes (Lamp1 and -2), indicating entrance into pathways for protein degradation. Altogether these observations indicate that an IE and/or E HCMV protein(s) downregulates the expression of PDGFR-alpha and -beta in SMCs. This phenomenon may disrupt cellular processes of importance in connection with cellular differentiation, migration, and/or proliferation. These observations may explain why congenital infection with HCMV can cause fetal brain damage. PMID- 17344285 TI - Biologic, antigenic, and full-length genomic characterization of a bovine-like coronavirus isolated from a giraffe. AB - Coronaviruses (CoVs) possess large RNA genomes and exist as quasispecies, which increases the possibility of adaptive mutations and interspecies transmission. Recently, CoVs were recognized as important pathogens in captive wild ruminants. This is the first report of the isolation and detailed genetic, biologic, and antigenic characterization of a bovine-like CoV from a giraffe (Giraffa camelopardalis) in a wild-animal park in the United States. CoV particles were detected by immune electron microscopy in fecal samples from three giraffes with mild-to-severe diarrhea. From one of the three giraffe samples, a CoV (GiCoV-OH3) was isolated and successfully adapted to serial passage in human rectal tumor 18 cell cultures. Hemagglutination assays, receptor-destroying enzyme activity, hemagglutination inhibition, and fluorescence focus neutralization tests revealed close biological and antigenic relationships between the GiCoV-OH3 isolate and selected respiratory and enteric bovine CoV (BCoV) strains. When orally inoculated into a BCoV-seronegative gnotobiotic calf, GiCoV-OH3 caused severe diarrhea and virus shedding within 2 to 3 days. Sequence comparisons and phylogenetic analyses were performed to assess its genetic relatedness to other CoVs. Molecular characterization confirmed that the new isolate belongs to group 2a of the mammalian CoVs and revealed closer genetic relatedness between GiCoV OH3 and the enteric BCoVs BCoV-ENT and BCoV-DB2, whereas BCoV-Mebus was more distantly related. Detailed sequence analysis of the GiCoV-OH3 spike gene demonstrated the presence of a deletion in the variable region of the S1 subunit (from amino acid 543 to amino acid 547), which is a region associated with pathogenicity and tissue tropism for other CoVs. The point mutations identified in the structural proteins (by comparing GiCoV-OH3, BCoV-ENT, BCoV-DB2, and BCoV Mebus) were most conserved among GiCoV-OH3, BCoV-ENT, and BCoV-DB2, whereas most of the point mutations in the nonstructural proteins were unique to GiCoV-OH3. Our results confirm the existence of a bovine-like CoV transmissible to cattle from wild ruminants, namely, giraffes, but with certain genetic properties different from those of BCoVs. PMID- 17344286 TI - Severe acute respiratory syndrome coronavirus accessory protein 6 is a virion associated protein and is released from 6 protein-expressing cells. AB - Analysis of severe acute respiratory syndrome coronavirus (SCoV) by either sucrose gradient equilibrium centrifugation or a virus capture assay using an anti-SCoV S protein antibody demonstrated that the SCoV 6 protein, which is one of the accessory proteins of SCoV, was incorporated into virus particles. Coexpression of the SCoV S, M, E, and 6 proteins was sufficient for incorporation of the 6 protein into virus-like particles. Cells transfected with plasmid expressing the 6 protein released SCoV 6 protein; however, infected cells released SCoV 6 protein only in association with SCoV particles. PMID- 17344287 TI - Antiviral effects of antisense morpholino oligomers in murine coronavirus infection models. AB - The recent emergence of novel pathogenic human and animal coronaviruses has highlighted the need for antiviral therapies that are effective against a spectrum of these viruses. We have used several strains of murine hepatitis virus (MHV) in cell culture and in vivo in mouse models to investigate the antiviral characteristics of peptide-conjugated antisense phosphorodiamidate morpholino oligomers (P-PMOs). Ten P-PMOs directed against various target sites in the viral genome were tested in cell culture, and one of these (5TERM), which was complementary to the 5' terminus of the genomic RNA, was effective against six strains of MHV. Further studies were carried out with various arginine-rich peptides conjugated to the 5TERM PMO sequence in order to evaluate efficacy and toxicity and thereby select candidates for in vivo testing. In uninfected mice, prolonged P-PMO treatment did not result in weight loss or detectable histopathologic changes. 5TERM P-PMO treatment reduced viral titers in target organs and protected mice against virus-induced tissue damage. Prophylactic 5TERM P-PMO treatment decreased the amount of weight loss associated with infection under most experimental conditions. Treatment also prolonged survival in two lethal challenge models. In some cases of high-dose viral inoculation followed by delayed treatment, 5TERM P-PMO treatment was not protective and increased morbidity in the treated group, suggesting that P-PMO may cause toxic effects in diseased mice that were not apparent in the uninfected animals. However, the strong antiviral effect observed suggests that with further development, P-PMO may provide an effective therapeutic approach against a broad range of coronavirus infections. PMID- 17344288 TI - Influenza virus infection causes specific degradation of the largest subunit of cellular RNA polymerase II. AB - It has been described that influenza virus polymerase associates with RNA polymerase II (RNAP II). To gain information about the role of this interaction, we explored if changes in RNAP II occur during infection. Here we show that influenza virus causes the specific degradation of the hypophosphorylated form of the largest subunit of RNAP II without affecting the accumulation of its hyperphosphorylated forms. This effect is independent of the viral strain and the origin of the cells used. Analysis of synthesized mRNAs in isolated nuclei of infected cells indicated that transcription decreases concomitantly with RNAP II degradation. Moreover, this degradation correlated with the onset of viral transcription and replication. The ubiquitin-mediated proteasome pathway is not involved in virally induced RNAP II proteolysis. The expression of viral polymerase from its cloned cDNAs was sufficient to cause the degradation. Since the PA polymerase subunit has proteolytic activity, we tested its participation in the process. A recombinant virus that encodes a PA point mutant with decreased proteolytic activity and that has defects in replication delayed the effect, suggesting that PA's contribution to RNAP II degradation occurs during infection. PMID- 17344289 TI - Herpes simplex virus immediate-early protein ICP22 triggers loss of serine 2 phosphorylated RNA polymerase II. AB - During eukaryotic mRNA transcription, the synthetic activity and mRNA processing factor interactions of RNA polymerase II (RNAP II) are regulated by phosphorylation of its carboxyl-terminal domain (CTD), with modification occurring primarily on serines 2 and 5 of the CTD. We previously showed that herpes simplex virus type 1 (HSV-1) infection rapidly triggers the loss of RNAP II forms bearing serine 2 phosphorylation (Ser-2P RNAP II). Here we show that the HSV-1 immediate-early (IE) protein ICP22 is responsible for this effect during the IE phase of infection. This activity does not require the viral UL13 protein kinase, which is required for several other regulatory functions of ICP22. Additionally, we show that transient expression of ICP22 can trigger the loss of Ser-2P RNAP II in transfected cells. Thus, the ability of ICP22 to cause the loss of Ser-2 RNAP II does not require other viral factors or the context of the infected cell. Expression of the HSV-1 ICP22-related protein US1.5, which corresponds to residues 147 to 420 of ICP22, also triggers a loss of Ser-2P RNAP II in transfected cells, whereas expression of the varicella-zoster virus ICP22 homolog, ORF63, does not. Our study also provides evidence for a second, viral late gene-dependent pathway that triggers loss of Ser-2P RNAP II in infected cells, consistent with the recent work of Dai-Ju et al. (J. Q. Dai-Ju, L. Li, L. A. Johnson, and R. M. Sandri-Goldin, J. Virol. 80:3567-3581, 2006). Therefore, it appears that HSV-1 has evolved redundant mechanisms for triggering the loss of a specific phosphorylated form of RNAP II. PMID- 17344290 TI - N-terminal mutants of herpes simplex virus type 2 gH are transported without gL but require gL for function. AB - Glycoprotein H (gH) is conserved among all herpesviruses and is essential for virus entry and cell fusion along with gL, gB, and, in most alphaherpesviruses, gD. Within the gH/gL heterodimer, it is thought that gH accounts for the fusion function and gL acts as a chaperone for the folding and transport of gH. Here, we found that the N terminus of gH2 contains important elements involved in both its folding and its transport. Our conclusions are based on the phenotypes of a series of gH deletion mutants in which the signal sequence (residues 1 to 18) was retained and N-terminal residues were removed up to the number indicated. The first mutant, gH2Delta29 (deletion of residues 19 to 28), like wild-type (WT) gH, required gL for both transport and function. To our surprise, two other mutants (gH2Delta64 and gH2Delta72) were transported to the cell surface independent of gL but were nonfunctional, even when complexed with gL. Importantly, a fourth mutant (gH2Delta48) was transported independent of gL but was functional only when complexed with gL. Using a panel of monoclonal antibodies against gH2, we found that when gH2Delta48 was expressed alone, its antigenic structure differed from that of gH2Delta48/gL or gH2-WT/gL. Mutation of gH2 residue R39, Y41, W42, or D44 allowed gL-independent transport of gH. Our results also show that gL is not merely required for gH transport but is also necessary for the folding and function of the complex. Since gH2Delta64/gL and gH2Delta72/gL were nonfunctional, we hypothesized that residues critical for gH/gL function lie within this deleted region. Additional mutagenesis identified L66 and L72 as important for function. Together, our results highlight several key gH residues: R39, Y41, W42, and D44 for gH transport and L66 and L72 for gH/gL structure and function. PMID- 17344291 TI - Preferential selection of human T-cell leukemia virus type 1 provirus lacking the 5' long terminal repeat during oncogenesis. AB - In adult T-cell leukemia (ATL) cells, a defective human T-cell leukemia virus type 1 (HTLV-1) provirus lacking the 5' long terminal repeat (LTR), designated type 2 defective provirus, is frequently observed. To investigate the mechanism underlying the generation of the defective provirus, we sequenced HTLV-1 provirus integration sites from cases of ATL. In HTLV-1 proviruses retaining both LTRs, 6 bp repeat sequences were adjacent to the 5' and 3' LTRs. In 8 of 12 cases with type 2 defective provirus, 6-bp repeats were identified at both ends. In five of these cases, a short repeat was bound to CA dinucleotides of the pol and env genes at the 5' end, suggesting that these type 2 defective proviruses were formed before integration. In four cases lacking the 6-bp repeat, short (6- to 26 bp) deletions in the host genome were identified, indicating that these defective proviruses were generated after integration. Quantification indicated frequencies of type 2 defective provirus of less than 3.9% for two carriers, which are much lower than those seen for ATL cases (27.8%). In type 2 defective proviruses, the second exons of the tax, rex, and p30 genes were frequently deleted, leaving Tax unable to activate NF-kappaB and CREB pathways. The HTLV-1 bZIP factor gene, located on the minus strand, is expressed in ATL cells with this defective provirus, and its coding sequences are intact, suggesting its significance in oncogenesis. PMID- 17344292 TI - Epigenetic status of an adenovirus type 12 transgenome upon long-term cultivation in hamster cells. AB - The epigenetic status of integrated adenovirus type 12 (Ad12) DNA in hamster cells cultivated for about 4 decades has been investigated. Cell line TR12, a fibroblastic revertant of the Ad12-transformed epitheloid hamster cell line T637 with 15 copies of integrated Ad12 DNA, carries one Ad12 DNA copy plus a 3.9-kbp fragment from a second copy. The cellular insertion site for the Ad12 integrate, identical in both cell lines, is a >5.2-kbp inverted DNA repeat. The Ad12 transgenome is packaged around nucleosomes. The cellular junction is more sensitive to micrococcal nuclease at Ad12-occupied sites than at unoccupied sites. Bisulfite sequencing reveals complete de novo methylation in most of the 1,634 CpGs of the integrated viral DNA, except for its termini. Isolated unmethylated CpGs extend over the entire Ad12 integrate. The fully methylated transgenome segments are characterized by promoter silencing and histone H3 and H4 hypoacetylation. Nevertheless, there is minimal transcriptional activity of the late viral genes controlled by the fully methylated major late promoter of Ad12 DNA. PMID- 17344293 TI - Demonstration of coinfection with and recombination by caprine arthritis encephalitis virus and maedi-visna virus in naturally infected goats. AB - Recombination of different strains and subtypes is a hallmark of lentivirus infections, particularly for human immunodeficiency virus, and contributes significantly to viral diversity and evolution both within individual hosts and within populations. Recombinant viruses are generated in individuals coinfected or superinfected with more than one lentiviral strain or subtype. This, however, has never been described in vivo for the prototype lentivirus maedi-visna virus of sheep and its closely related caprine counterpart, the caprine arthritis encephalitis virus. Cross-species infections occur in animals living under natural conditions, which suggests that dual infections with small-ruminant lentiviruses (SRLVs) are possible. In this paper we describe the first documented case of coinfection and viral recombination in two naturally infected goats. DNA fragments encompassing a variable region of the envelope glycoprotein were obtained from these two animals by end-limiting dilution PCR of peripheral blood mononuclear cells or infected cocultures. Genetic analyses, including nucleotide sequencing and heteroduplex mobility assays, showed that these goats harbored two distinct populations of SRLVs. Phylogenetic analysis permitted us to assign these sequences to the maedi-visna virus group (SRLV group A) or the caprine arthritis encephalitis virus group (SRLV group B). SimPlot analysis showed clear evidence of A/B recombination within the env gene segment of a virus detected in one of the two goats. This case provides conclusive evidence that coinfection by different strains of SRLVs of groups A and B can indeed occur and that these viruses actually recombine in vivo. PMID- 17344294 TI - Identification of determinants involved in initiation of hepatitis C virus RNA synthesis by using intergenotypic replicase chimeras. AB - The 5' nontranslated region (NTR) and the X tail in the 3' NTR are the least variable parts of the hepatitis C virus (HCV) genome and play an important role in the initiation of RNA synthesis. By using subgenomic replicons of the HCV isolates Con1 (genotype 1) and JFH1 (genotype 2), we characterized the genotype specificities of the replication signals contained in the NTRs. The replacement of the JFH1 5' NTR and X tail with the corresponding Con1 sequence resulted in a significant decrease in replication efficiency. Exchange of the X tail specifically reduced negative-strand synthesis, whereas substitution of the 5' NTR impaired the generation of progeny positive strands. In search for the proteins involved in the recognition of genotype-specific initiation signals, we analyzed recombinant nonstructural protein 5B (NS5B) RNA polymerases of both isolates and found some genotype-specific template preference for the 3' end of positive-strand RNA in vitro. To further address genotype specificity, we constructed a series of intergenotypic replicon chimeras. When combining NS3 to NS5A of Con1 with NS5B of JFH1, we observed more-efficient replication with the genotype 2a X tail, indicating that NS5B recognizes genotype-specific signals in this region. In contrast, a combination of the NS3 helicase with NS5A and NS5B was required to confer genotype specificity to the 5' NTR. These results present the first genetic evidence for an interaction between helicase, NS5A, and NS5B required for the initiation of RNA synthesis and provide a system for the specific analysis of HCV positive- and negative-strand syntheses. PMID- 17344295 TI - APOBEC3G multimers are recruited to the plasma membrane for packaging into human immunodeficiency virus type 1 virus-like particles in an RNA-dependent process requiring the NC basic linker. AB - APOBEC3G is an endogenous host restriction factor that inhibits human immunodeficiency virus (HIV) replication. The antiviral activity of APOBEC3G is dependent upon its incorporation into the virus particle. The mechanisms governing incorporation of APOBEC3G into virus particles are not completely understood. In particular, some investigators have reported that APOBEC3G interacts directly with the nucleocapsid (NC) subunit of Gag, while others have found that an RNA intermediate is required for Gag-APOBEC3G interactions. In this study, we confirmed the RNA dependence of APOBEC3G packaging and performed detailed mapping of the determinants within NC that are required for virion incorporation. Surprisingly, APOBEC3G packaging did not correlate well with the presence of the N-terminal "I," or interaction, domain within NC. Specifically, Gag constructs containing only the N-terminal region of NC packaged minimal amounts of APOBEC3G, while significant levels of APOBEC3G packaging were achieved with Gag constructs containing the basic linker region of NC. Furthermore, membrane-binding experiments revealed that the basic linker region was essential for the membrane association of APOBEC3G in a Gag-APOBEC3G complex. Fluorescence resonance energy transfer was detected between labeled APOBEC3G in cells and in particles, indicating that APOBEC3G is packaged as a multimer that is bound to packaged RNA. Regions of APOBEC3G-Gag colocalization at the plasma membrane were detected that were distinct from the punctate cytoplasmic bodies where APOBEC3G accumulates within the cell. Together, our results indicate that APOBEC3G multimerizes in an RNA-dependent fashion and that RNA-APOBEC3G multimers are recruited to the plasma membrane and subsequently into virion particles by Gag. PMID- 17344296 TI - Long-term control of simian immunodeficiency virus replication with central memory CD4+ T-cell preservation after nonsterile protection by a cytotoxic T lymphocyte-based vaccine. AB - Induction of virus-specific CD8(+) cytotoxic T-lymphocyte (CTL) responses is a promising strategy for AIDS vaccine development. However, it has remained unclear if or how long-term viral containment and disease control are attainable by CTL based nonsterile protection. Here, we present three rhesus macaques that successfully maintained Env-independent vaccine-based control of simian immunodeficiency virus (SIV) mac239 replication without disease progression for more than 3 years. SIV-specific neutralizing antibody induction was inefficient in these controllers. Vaccine-induced Gag-specific CTLs were crucial for the chronic as well as the primary viral control in one of them, whereas those Gag specific CTL responses became undetectable and CTLs specific for SIV antigens other than Gag, instead, became predominant in the chronic phase in the other two controllers. A transient CD8(+) cell depletion experiment 3 years postinfection resulted in transient reappearance of plasma viremia in these two animals, suggesting involvement of the SIV non-Gag-specific CTLs in the chronic SIV control. This sustained, neutralizing antibody-independent viral control was accompanied with preservation of central memory CD4(+) T cells in the chronic phase. Our results suggest that prophylactic CTL vaccine-based nonsterile protection can result in long-term viral containment by adapted CTL responses for AIDS prevention. PMID- 17344297 TI - A phylogenetically conserved RNA structure in the poliovirus open reading frame inhibits the antiviral endoribonuclease RNase L. AB - RNase L is an antiviral endoribonuclease that cleaves viral mRNAs after single stranded UA and UU dinucleotides. Poliovirus (PV) mRNA is surprisingly resistant to cleavage by RNase L due to an RNA structure in the 3C(Pro) open reading frame (ORF). The RNA structure associated with the inhibition of RNase L is phylogenetically conserved in group C enteroviruses, including PV type 1 (PV1), PV2, PV3, coxsackie A virus 11 (CAV11), CAV13, CAV17, CAV20, CAV21, and CAV24. The RNA structure is not present in other human enteroviruses (group A, B, or D enteroviruses). Coxsackievirus B3 mRNA and hepatitis C virus mRNA were fully sensitive to cleavage by RNase L. HeLa cells expressing either wild-type RNase L or a dominant-negative mutant RNase L were used to examine the effects of RNase L on PV replication. PV replication was not inhibited by RNase L activity, but rRNA cleavage characteristic of RNase L activity was detected late during the course of PV infection, after assembly of intracellular virus. Rather than inhibiting PV replication, RNase L activity was associated with larger plaques and better cell to-cell spread. Mutations in the RNA structure associated with the inhibition of RNase L did not affect the magnitude of PV replication in HeLa cells expressing RNase L, consistent with the absence of observed RNase L activity until after virus assembly. Thus, PV carries an RNA structure in the 3C protease ORF that potently inhibits the endonuclease activity of RNase L, but this RNA structure does not prevent RNase L activity late during the course of infection, as virus assembly nears completion. PMID- 17344298 TI - La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts. AB - La Crosse virus (LACV) is a mosquito-transmitted member of the Bunyaviridae family that causes severe encephalitis in children. For the LACV nonstructural protein NSs, previous overexpression studies with mammalian cells had suggested two different functions, namely induction of apoptosis and inhibition of RNA interference (RNAi). Here, we demonstrate that mosquito cells persistently infected with LACV do not undergo apoptosis and mount a specific RNAi response. Recombinant viruses that either express (rLACV) or lack (rLACVdelNSs) the NSs gene similarly persisted and were prone to the RNAi-mediated resistance to superinfection. Furthermore, in mosquito cells overexpressed LACV NSs was unable to inhibit RNAi against Semliki Forest virus. In mammalian cells, however, the rLACVdelNSs mutant virus strongly activated the antiviral type I interferon (IFN) system, whereas rLACV as well as overexpressed NSs suppressed IFN induction. Consequently, rLACVdelNSs was attenuated in IFN-competent mouse embryo fibroblasts and animals but not in systems lacking the type I IFN receptor. In situ analyses of mouse brains demonstrated that wild-type and mutant LACV mainly infect neuronal cells and that NSs is able to suppress IFN induction in the central nervous system. Thus, our data suggest little relevance of the NSs induced apoptosis or RNAi inhibition for growth or pathogenesis of LACV in the mammalian host and indicate that NSs has no function in the insect vector. Since deletion of the viral NSs gene can be fully complemented by inactivation of the host's IFN system, we propose that the major biological function of NSs is suppression of the mammalian innate immune response. PMID- 17344299 TI - In vivo fitness costs of different Gag CD8 T-cell escape mutant simian-human immunodeficiency viruses for macaques. AB - The kinetics of immune escape and reversion depend upon the efficiency of CD8 cytotoxic T lymphocytes (CTL) and the fitness cost of escape mutations. Escape kinetics of three simian immunodeficiency virus Gag CTL epitopes in pigtail macaques were variable; those of KP9 and AF9 were faster than those of KW9. Kinetics of reversion of escape mutant virus to wild type upon passage to naive major histocompatibility complex-mismatched macaques also varied. Rapid reversion occurred at KP9, gradual biphasic reversion occurred at AF9, and escape mutant KW9 virus failed to revert. The fitness impact of these mutations is KP9 > AF9 > KW9. These data provide insights into the differential utility of CTL in controlling viremia. PMID- 17344300 TI - Role of the sonchus yellow net virus N protein in formation of nuclear viroplasms. AB - Sonchus yellow net virus is a plant nucleorhabdovirus whose nucleocapsid (N), phosphoprotein (P), and polymerase (L) proteins form large viroplasms in the nuclei of infected plants (C. R. F. Martins, J. A. Johnson, D. M. Lawrence, T. J. Choi, A. Pisi, S. L. Tobin, D. Lapidus, J. D. O. Wagner, S. Ruzin, K. McDonald, and A. O. Jackson, J. Virol. 72:5669-5679, 1998). When expressed alone, the N protein localizes to the nuclei of plant and yeast (Saccharomyces cerevisiae) cells and the P protein is distributed throughout the cells, but coexpression of N and P results in formation of subnuclear viroplasm-like foci (M. M. Goodin, J. Austin, R. Tobias, M. Fujita, C. Morales, and A. O. Jackson, J. Virol. 75:9393 9406, 2001; M. M. Goodin, R. G. Dietzgen, D. Schichnes, S. Ruzin, and A. O. Jackson, Plant J. 31:375-383, 2002). We now show that the N protein and various fluorescent derivatives form similar subnuclear foci in plant cells and that homologous interactions mediated by a helix-loop-helix region near the amino terminus are required for formation of the foci. Mutations within the helix-loop helix region also interfere with N- and P-protein interactions that are required for N and P colocalization in the subnuclear foci. Affinity purification of N proteins harboring single mutations within the motif revealed that Tyr40 is critical for N-N and N-P interactions. Additional in vitro binding assays also indicated that the N protein binds to yeast and plant importin alpha homologues, whereas mutations in the carboxy-terminal nuclear localization signal abrogate importin alpha binding. The P protein did not bind to the importin alpha homologues, suggesting that the N and P proteins use different pathways for nuclear entry. Our results in toto support a model suggesting that during infection, the N and P proteins enter the nucleus independently, that viroplasm formation requires homologous N-protein interactions, and that P protein targeting to the viroplasm requires N-P protein interactions that occur after N and P protein import into the nucleus. PMID- 17344301 TI - Novel nuclear import of Vpr promoted by importin alpha is crucial for human immunodeficiency virus type 1 replication in macrophages. AB - Monocytes/macrophages are major targets of human immunodeficiency virus type 1 (HIV-1) infection. The viral preintegration complex (PIC) of HIV-1 enters the nuclei of monocyte-derived macrophages, but very little PIC migrates into the nuclei of immature monocytes. Vpr, one of the accessory gene products of HIV-1, is essential for the nuclear import of PIC in these cells, although the role of Vpr in the entry mechanism of PIC remains to be clarified. We have shown previously that Vpr is targeted to the nuclear envelope and then transported into the nucleus by importin alpha alone, in an importin beta-independent manner. Here we demonstrate that the nuclear import of Vpr is strongly promoted by the addition of cytoplasmic extract from macrophages but not of that from monocytes and that the nuclear import activity is lost with immunodepletion of importin alpha from the cytoplasmic extract. Immunoblot analysis and real-time PCR demonstrate that immature monocytes express importin alpha at low levels, whereas the expression of three major importin alpha isoforms markedly increases upon their differentiation into macrophages, indicating that the expression of importin alpha is required for nuclear import of Vpr. Furthermore, interaction between importin alpha and the N-terminal alpha-helical domain of Vpr is indispensable, not only for the nuclear import of Vpr but also for HIV-1 replication in macrophages. This study suggests the possibility that the binding of Vpr to importin alpha, preceding a novel nuclear import process, is a potential target for therapeutic intervention. PMID- 17344302 TI - Multifunctional human immunodeficiency virus (HIV) gag-specific CD8+ T-cell responses in rectal mucosa and peripheral blood mononuclear cells during chronic HIV type 1 infection. AB - The intestinal tract is a lymphocyte-rich site that undergoes severe depletion of memory CD4(+) T cells within days of simian immunodeficiency virus or human immunodeficiency virus type 1 (HIV-1) infection. An ensuing influx of virus specific CD8(+) T cells, which persist throughout the chronic phase of infection, has also been documented in the gastrointestinal tract. However, little is known of the functionality of these effector cells or their relationship to the disease course. In this study, we measured CD8(+) T-cell responses to HIV-1 peptides in paired rectal and blood samples from chronically infected patients. In both blood and rectum, there was an immunodominant CD8(+) T-cell response to HIV Gag compared to Pol and Env (P < 0.01). In contrast, cytomegalovirus pp65 peptides elicited gamma interferon (IFN-gamma) secretion strongly in peripheral blood mononuclear cells (PBMC) but weakly in rectal CD8(+) T cells (P = 0.015). Upon stimulation with HIV peptides, CD8(+) T cells from both sites were capable of mounting complex responses including degranulation (CD107 expression) and IFN gamma and tumor necrosis factor alpha (TNF-alpha) production. In rectal tissue, CD107 release was frequently coupled with production of IFN-gamma or TNF-alpha. In patients not on antiretroviral therapy, the magnitude of Gag-specific responses, as a percentage of CD8(+) T cells, was greater in the rectal mucosa than in PBMC (P = 0.054); however, the breakdown of responding cells into specific functional categories was similar in both sites. These findings demonstrate that rectal CD8(+) T cells are capable of robust and varied HIV-1 specific responses and therefore likely play an active role in eliminating infected cells during chronic infection. PMID- 17344303 TI - Sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion. AB - Previously, we reported that treatment of cells with sphingomyelinase inhibits human immunodeficiency virus type 1 (HIV-1) entry. Here, we determined by measuring fluorescence recovery after photobleaching that the lateral diffusion of CD4 decreased 4-fold following sphingomyelinase treatment, while the effective diffusion rate of CCR5 remained unchanged. Notably, sphingomyelinase treatment of cells did not influence gp120 binding, HIV-1 attachment, or fluid-phase and receptor-mediated endocytosis. Furthermore, sphingomyelinase treatment did not affect the membrane disposition of the HIV receptor proteins CD4, CXCR4, and CCR5, as determined by Triton X-100 extraction. Restriction of CD4 diffusion by antibody cross-linking also inhibited HIV infection. We therefore interpret the decrease in CD4 lateral mobility following sphingomyelinase treatment in terms of clustering of CD4 molecules. Examination of fusion intermediates indicated that sphingomyelinase treatment inhibited HIV at a step in the fusion process after CD4 engagement. Maximal inhibition of fusion was observed following short coculture times and with target cells that express low levels of CD4. As HIV entry into cells requires the sequential engagement of viral envelope protein with CD4 and coreceptor, we propose that sphingomyelinase inhibits HIV infection by inducing CD4 clustering that prevents coreceptor engagement and HIV fusion. PMID- 17344304 TI - Artificial microRNA-mediated virus resistance in plants. AB - RNA silencing in plants is a natural defense system against foreign genetic elements including viruses. This natural antiviral mechanism has been adopted to develop virus-resistant plants through expression of virus-derived double stranded RNAs or hairpin RNAs, which in turn are processed into small interfering RNAs (siRNAs) by the host's RNA silencing machinery. While these virus-specific siRNAs were shown to be a hallmark of the acquired virus resistance, the functionality of another set of the RNA silencing-related small RNAs, microRNAs (miRNAs), in engineering plant virus resistance has not been extensively explored. Here we show that expression of an artificial miRNA, targeting sequences encoding the silencing suppressor 2b of Cucumber mosaic virus (CMV), can efficiently inhibit 2b gene expression and protein suppressor function in transient expression assays and confer on transgenic tobacco plants effective resistance to CMV infection. Moreover, the resistance level conferred by the transgenic miRNA is well correlated to the miRNA expression level. Comparison of the anti-CMV effect of the artificial miRNA to that of a short hairpin RNA derived small RNA targeting the same site revealed that the miRNA approach is superior to the approach using short hairpin RNA both in transient assays and in transgenic plants. Together, our data demonstrate that expression of virus specific artificial miRNAs is an effective and predictable new approach to engineering resistance to CMV and, possibly, to other plant viruses as well. PMID- 17344305 TI - Fitness declines in Tobacco etch virus upon serial bottleneck transfers. AB - It has been well established that populations of RNA viruses transmitted throughout serial bottlenecks suffer from significant fitness declines as a consequence of the accumulation of deleterious mutations by the onset of Muller's ratchet. Bottlenecks are unavoidably linked to different steps of the infectious cycle of most plant RNA viruses, such as vector-mediated transmissions and systemic colonization of new leaves. Here we report evidence for fitness declines by the accumulation of deleterious mutations in the potyvirus Tobacco etch virus (TEV). TEV was inoculated into the nonsystemic host Chenopodium quinoa, and local lesions were isolated and used to initiate 20 independent mutation accumulation lineages. Weekly, a random lesion from each lineage was isolated and used to inoculate the next set of plants. At each transfer, the Malthusian growth rate was estimated. After 11 consecutive transfers, all lineages suffered significant fitness losses, and one even became extinct. The average rate of fitness decline was 5% per day. The average pattern of fitness decline was consistent with antagonistic epistasis between deleterious mutations, as postulated for antiredundant genomes. Temporal fitness fluctuations were not explained by random noise but reflected more complex underlying processes related to emergence and self-organization phenomena. PMID- 17344307 TI - Brugada-like electrocardiographic pattern and ventricular fibrillation in a patient with primary hyperparathyroidism. AB - There are several causes for ST segment abnormalities in leads V1 to V3. Hypercalcaemia and Brugada syndrome are among them. Both are known to produce ventricular arrhythmia, albeit only rare cases have been reported with documented evidence of ventricular arrhythmias in association with a hypercalcaemic crisis but none when hypercalcaemic coexists with Brugada syndrome. We describe a patient with primary hyperparathyroidism who presented with ventricular fibrillation, and the ECG showed changes similar to Brugada syndrome. The provocation test with flecainide was conducted twice. This was positive, both before and after parathyroidectomy when serum calcium and parathormone levels had normalized. The patient was treated for hypercalcaemia and underwent parathyroidectomy. This is the first report of oral flecainide test unmasking the diagnostic coved Brugada ECG pattern in a patient with primary hyperparathyroidism and raising attention to hypercalcaemia as a potential trigger for life-threatening arrhythmia in Brugada syndrome. PMID- 17344306 TI - Incorporation of human immunodeficiency virus type 1 reverse transcriptase into virus-like particles. AB - We demonstrate that a genetically engineered human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) composed mainly of p66 or p51 subunits can be incorporated into virus-like particles (VLPs) when coexpressed with HIV-1 Pr55(gag). VLP-associated RT exhibited a detergent-resistant association with immature cores during sucrose gradient equilibrium centrifugation, suggesting that RT is incorporated into VLPs. However, RT that retains downstream integrase (IN) is severely inhibited in terms of incorporation into VLPs. Results from immunofluorescence tests reveal that RT-IN is primarily localized at the perinuclear area and exhibits poor colocalization with Gag. IN removal leads to a redistribution of RT throughout the cytoplasm and improved RT incorporation into VLPs. Similar results were observed for RT-IN in which alanine was substituted for 186-Lys-Arg-Lys-188 residues of the IN putative nuclear localization signal, suggesting that IN karyophilic properties may partly account for the inhibitory effect of IN on RT incorporation. Although the membrane-binding capacity of RT was markedly reduced compared to that of wild-type Gag or Gag-Pol, the correlation of membrane-binding ability with particle incorporation efficiency was incomplete. Furthermore, we observed that membrane-binding-defective myristylation-minus RT can be packaged into VLPs at the same level as its normal myristylated counterpart. This suggests that the incorporation of RT into VLPs is independent of membrane affinity but very dependent on RT-Gag interaction. Results from a genetic analysis suggest that the Gag-interacting regions of RT mainly reside in the thumb subdomain and that the RT-binding domains of Gag are located in the matrix (MA) and p6 regions. PMID- 17344308 TI - Attenuation of ECG voltage in cirrhotic patients. AB - Two patients with cirrhosis (CIR), ascites (ASC), and peripheral oedema (PEROD) are presented. They were followed for many years, had multiple hospital admissions and clinic evaluations, had repeated laboratory testing, and many ECGs recorded. As their condition worsened, they developed attenuation of the ECG voltage (ATTECGV), which was more pronounced during intervals of increased fluid overload. Attenuation of the ECG voltage was decreased at times of successful diuresis and amelioration of PEROD, while abdominal paracenteses for ASC did not have any influence on the ATTECGV, suggesting that ATTECGV in patients with CIR is due to the associated PEROD, and not to ASC. PMID- 17344309 TI - Upregulation of gamma-glutamate-cysteine ligase as part of the long-term adaptation process to iron accumulation in neuronal SH-SY5Y cells. AB - Reactive iron is an important prooxidant factor, whereas GSH is a crucial component of a long-term adaptive system that allows cells to function during extended periods of high oxidative stress. In this work, the adaptive response of the GSH system to prolonged iron loads was characterized in human dopaminergic SH SY5Y neuroblastoma cells. After the initial death of a substantial portion of the cell population, the surviving cells increased their GSH content by up to fivefold. This increase was traced to increased expression of the catalytic and modulatory subunits of gamma-glutamate-cysteine ligase. Under conditions of high iron load, cells maintained a low GSSG content through two mechanisms: 1) GSSG reductase-mediated recycling of GSSG to GSH and 2) multidrug resistant protein 1 mediated extrusion of GSSG. Increased GSH synthesis and low GSSG levels contributed to recover the cell reduction potential from -290 mV at the time of cell death to about -320 mV. These results highlight the fundamental role of GSH homeostasis in the antioxidant response to cellular iron accumulation and provide novel insights into the adaptive mechanisms of neurons subjected to increased iron loads, such as those observed in Parkinson's disease. PMID- 17344310 TI - Autoactivation of matriptase in vitro: requirement for biomembrane and LDL receptor domain. AB - In live cells, autoactivation of matriptase, a membrane-bound serine protease, can be induced by lysophospholipids, androgens, and the polyanionic compound suramin. These structurally distinct chemicals induce different signaling pathways and cellular events that somehow, in a cell type-specific manner, lead to activation of matriptase immediately followed by inhibition of matriptase by hepatocyte growth factor activator inhibitor 1 (HAI-1). In the current study, we established an analogous matriptase autoactivation system in an in vitro cell free setting and showed that a burst of matriptase activation and HAI-1-mediated inhibition spontaneously occurred in the insoluble fractions of cell homogenates and that this in vitro activation could be attenuated by a soluble suppressive factor(s) in cytosolic fractions. Immunofluorescence staining and subcellular fractionation studies revealed that matriptase activation occurred in the perinuclear regions. Solubilization of matriptase from cell homogenates by Triton X-100 or sonication of cell homogenates completely inhibited the effect, suggesting that matriptase activation requires proper lipid bilayer microenvironments, potentially allowing appropriate interactions of matriptase zymogens with HAI-1 and other components. Matriptase activation occurred in a narrow pH range (from pH 5.2 to 7.2), with a sharp increase in activation at the transition from pH 5.2 to 5.4, and could be completely suppressed by moderately increased ionic strength. Protease inhibitors only modestly affected activation, whereas 30 nM (5 microg/ml) of anti-matriptase LDL receptor domain 3 monoclonal antibodies completely blocked activation. These atypical biochemical features are consistent with a mechanism for autoactivation of matriptase that requires protein-protein interactions but not active proteases. PMID- 17344311 TI - Role of glycolytically generated ATP for CaMKII-mediated regulation of intracellular Ca2+ signaling in bovine vascular endothelial cells. AB - The role of glycolytically generated ATP in Ca(2+)/calmodulin-dependent kinase II (CaMKII)-mediated regulation of intracellular Ca(2+) signaling was examined in cultured calf pulmonary artery endothelial (CPAE) cells. Exposure of cells (extracellular Ca(2+) concentration = 2 mM) to glycolytic inhibitors 2-deoxy-D glucose (2-DG), pyruvate (pyr) + beta-hydroxybutyrate (beta-HB), or iodoacetic acid (IAA) caused an increase of intracellular Ca(2+) concentration ([Ca(2+)](i)). CaMKII inhibitors (KN-93, W-7) triggered a similar increase of [Ca(2+)](i). The rise of [Ca(2+)](i) was characterized by a transient spike followed by a small sustained plateau of elevated [Ca(2+)](i). In the absence of extracellular Ca(2+) 2-DG caused an increase in [Ca(2+)](i), suggesting that inhibition of glycolysis directly triggered release of Ca(2+) from intracellular endoplasmic reticulum (ER) Ca(2+) stores. The inositol-1,4,5-trisphosphate receptor (IP(3)R) inhibitor 2-aminoethoxydiphenyl borate abolished the KN-93- and 2-DG-induced Ca(2+) response. Ca(2+) release was initiated in peripheral cytoplasmic processes from which activation propagated as a [Ca(2+)](i) wave toward the central region of the cell. Focal application of 2-DG resulted in spatially confined elevations of [Ca(2+)](i). Propagating [Ca(2+)](i) waves were preceded by [Ca(2+)](i) oscillations and small, highly localized elevations of [Ca(2+)](i) (Ca(2+) puffs). Inhibition of glycolysis with 2-DG reduced the KN-93 induced Ca(2+) response, and vice versa during inhibition of CaMKII 2-DG-induced Ca(2+) release was attenuated. Similar results were obtained with pyr + beta-HB and W-7. Furthermore, 2-DG and IAA caused a rapid increase of intracellular Mg(2+) concentration, indicating a concomitant drop of cellular ATP levels. In conclusion, CaMKII exerts a profound inhibition of ER Ca(2+) release in CPAE cells, which is mediated by glycolytically generated ATP, possibly through ATP dependent phosphorylation of the IP(3)R. PMID- 17344312 TI - S-acylation regulates Kv1.5 channel surface expression. AB - The number of ion channels expressed on the cell surface shapes the complex electrical response of excitable cells. An imbalance in the ratio of inward and outward conducting channels is unfavorable and often detrimental. For example, over- or underexpression of voltage-gated K(+) (Kv) channels can be cytotoxic and in some cases lead to disease. In this study, we demonstrated a novel role for S acylation in Kv1.5 cell surface expression. In transfected fibroblasts, biochemical evidence showed that Kv1.5 is posttranslationally modified on both the NH(2) and COOH termini via hydroxylamine-sensitive thioester bonds. Pharmacological inhibition of S-acylation, but not myristoylation, significantly decreased Kv1.5 expression and resulted in accumulation of channel protein in intracellular compartments and targeting for degradation. Channel protein degradation was rescued by treatment with proteasome inhibitors. Time course experiments revealed that S-acylation occurred in the biosynthetic pathway of nascent channel protein and showed that newly synthesized Kv1.5 protein, but not protein expressed on the cell surface, is sensitive to inhibitors of thioacylation. Sensitivity to inhibitors of S-acylation was governed by COOH terminal, but not NH(2)-terminal, cysteines. Surprisingly, although intracellular cysteines were required for S-acylation, mutation of these residues resulted in an increase in Kv1.5 cell surface channel expression, suggesting that screening of free cysteines by fatty acylation is an important regulatory step in the quality control pathway. Together, these results show that S-acylation can regulate steady-state expression of Kv1.5. PMID- 17344313 TI - Cardiac mitochondrial bioenergetics, oxidative stress, and aging. AB - Mitochondria have been a central focus of several theories of aging as a result of their critical role in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function coupled with the accumulation of oxidative damage to macromolecules may be causal to the decline in cardiac performance with age. In contrast, regular physical activity and lifelong caloric restriction can prevent oxidative stress, delay the onset of morbidity, increase life span, and reduce the risk of developing several pathological conditions. The health benefits of life long exercise and caloric restriction may be, at least partially, due to a reduction in the chronic amount of mitochondrial oxidant production. In addition, the available data suggest that chronic exercise may serve to enhance antioxidant enzyme activities, and augment certain repair/removal pathways, thereby reducing the amount of oxidative tissue damage. However, the characterization of age-related changes to cardiac mitochondria has been complicated by the fact that two distinct populations of mitochondria exist in the myocardium: subsarcolemmal mitochondria and interfibrillar mitochondria. Several studies now suggest the importance of studying both mitochondrial populations when attempting to elucidate the contribution of mitochondrial dysfunction to myocardial aging. The role that mitochondrial dysfunction and oxidative stress play in contributing to cardiac aging will be discussed along with the use of lifelong exercise and calorie restriction as countermeasures to aging. PMID- 17344314 TI - Molecular mechanism of rat NHE3 gene promoter regulation by sodium butyrate. AB - Sodium butyrate (NaB) stimulates sodium and water absorption by inducing colonic Na(+)/H(+) exchange. NaB induces Na(+)/H(+) exchanger (NHE)3 activity and protein and mRNA expression both in vivo and in vitro. Our previously published observations indicated that this induction is Ser/Thr kinase dependent and that NaB-responsive elements were localized within -320/-34 bp of the rat NHE3 promoter. Here we further delineate the mechanism of NaB-mediated NHE3 gene transcription. Transient and stable transfection of Caco-2 cells with NHE3 gene reporter constructs identified Sp binding site SpB at position -58/-55 nt as critical for NaB-mediated induction. Gel mobility shift (GMSA) and DNA affinity precipitation assays indicated NaB-induced binding of Sp3 and decreased binding of Sp1 to SpB element. While no changes in expression of Sp1 or Sp3 were noted, NaB induced phosphorylation of Sp1 and acetylation of Sp3. Sp3 was a more potent inducer of NHE3 gene transcription, which suggested that change in balance, favoring binding of Sp3 to the SpB site, would result in significant increase in NHE3 promoter activity. Small interfering RNA studies in Caco-2 cells and data from NaB-treated SL2 cells used as a reconstitution model confirmed this hypothesis. In addition to the SpB site, which played a permissive role, an upstream novel butyrate response element located at -196/-175 nt was necessary for maximal induction. GMSA identified a protein-DNA complex with a -196/-175 nt probe; this interaction was not affected by NaB treatment, thus suggesting that in response to NaB Sp3 binding to site SpB precedes and results in recruitment of the putative factor to this upstream site. PMID- 17344315 TI - Effect of Ca2+ on cardiac mitochondrial energy production is modulated by Na+ and H+ dynamics. AB - The energy production of mitochondria in heart increases during exercise. Several works have suggested that calcium acts at multiple control points to activate net ATP production in what is termed "parallel activation". To study this, a computational model of mitochondrial energy metabolism in the heart has been developed that integrates the Dudycha-Jafri model for the tricarboxylic acid cycle with the Magnus-Keizer model for mitochondrial energy metabolism and calcium dynamics. The model improves upon the previous formulation by including an updated formulation for calcium dynamics, and new descriptions of sodium, hydrogen, phosphate, and ATP balance. To this end, it incorporates new formulations for the calcium uniporter, sodium-calcium exchange, sodium-hydrogen exchange, the F(1)F(0)-ATPase, and potassium-hydrogen exchange. The model simulates a wide range of experimental data, including steady-state and simulated pacing protocols. The model suggests that calcium is a potent activator of net ATP production and that as pacing increases energy production due to calcium goes up almost linearly. Furthermore, it suggests that during an extramitochondrial calcium transient, calcium entry and extrusion cause a transient depolarization that serve to increase NADH production by the tricarboxylic acid cycle and NADH consumption by the respiration driven proton pumps. The model suggests that activation of the F(1)F(0)-ATPase by calcium is essential to increase ATP production. In mitochondria very close to the release sites, the depolarization is more severe causing a temporary loss of ATP production. However, due to the short duration of the depolarization the net ATP production is also increased. PMID- 17344316 TI - Effects of elevated physiological temperatures on sarcoplasmic reticulum function in mechanically skinned muscle fibers of the rat. AB - Properties of the sarcoplasmic reticulum (SR) with respect to Ca(2+) loading and release were measured in mechanically skinned fiber preparations from isolated extensor digitorum longus (EDL) muscles of the rat that were either kept at room temperature (23 degrees C) or exposed to temperatures in the upper physiological range for mammalian skeletal muscle (30 min at 40 or 43 degrees C). The ability of the SR to accumulate Ca(2+) was significantly reduced by a factor of 1.9-2.1 after the temperature treatments due to a marked increase in SR Ca(2+) leak, which persisted for at least 3 h after treatment. Results with blockers of Ca(2+) release channels (ruthenium red) and SR Ca(2+) pumps [2,5-di(tert-butyl)-1,4 hydroquinone] indicate that the increased Ca(2+) leak was not through the SR Ca(2+) release channel or the SR Ca(2+) pump, although it is possible that the leak pathway was via oligomerized Ca(2+) pump molecules. No significant change in the maximum SR Ca(2+)-ATPase activity was observed after the temperature treatment, although there was a tendency for a decrease in the SR Ca(2+)-ATPase. The observed changes in SR properties were fully prevented by the superoxide (O(2)(*-)) scavenger Tiron (20 mM), indicating that the production of O(2)(*-) at elevated temperatures is responsible for the increase in SR Ca(2+) leak. Results show that physiologically relevant elevated temperatures 1) induce lasting changes in SR properties with respect to Ca(2+) handling that contribute to a marked increase in the SR Ca(2+) leak and, consequently, to the reduction in the average coupling ratio between Ca(2+) transport and SR Ca(2+)-ATPase and muscle performance, and 2) that these changes are mediated by temperature-induced O(2)(* ) production. PMID- 17344317 TI - Cancer-derived p53 mutants suppress p53-target gene expression--potential mechanism for gain of function of mutant p53. AB - Tumour-derived p53 mutants are thought to have acquired 'gain-of-function' properties that contribute to oncogenicity. We have tested the hypothesis that p53 mutants suppress p53-target gene expression, leading to enhanced cellular growth. Silencing of mutant p53 expression in several human cell lines was found to lead to the upregulation of wild-type p53-target genes such as p21, gadd45, PERP and PTEN. The expression of these genes was also suppressed in H1299-based isogenic cell lines expressing various hot-spot p53 mutants, and silencing of mutant p53, but not TAp73, abrogated the suppression. Consistently, these hot spot p53 mutants were able to suppress a variety of p53-target gene promoters. Analysis using the proto-type p21 promoter construct indicated that the p53 binding sites are dispensable for mutant p53-mediated suppression. However, treatment with the histone deacetylase inhibitor trichostatin-A resulted in relief of mutant p53-mediated suppression, suggesting that mutant p53 may induce hypo-acetylation of target gene promoters leading to the suppressive effects. Finally, we show that stable down-regulation of mutant p53 expression resulted in reduced cellular colony growth in human cancer cells, which was found to be due to the induction of apoptosis. Together, the results demonstrate another mechanism through which p53 mutants could promote cellular growth. PMID- 17344318 TI - Role of GAC63 in transcriptional activation mediated by beta-catenin. AB - Beta-catenin is a key mediator in the canonical Wnt signaling pathway, which plays important roles in multiple developmental processes. Inappropriate activation of this pathway leads to developmental defects and development of certain cancers. Upon Wnt signaling, beta-catenin binds TCF/LEF transcription factors. The TCF/LEF-beta-catenin complex then recruits a variety of transcriptional coactivators to the promoter/enhancer region of Wnt-responsive genes and activates target gene transcription. In this article, we demonstrate that GRIP1-associated coactivator 63 (GAC63), a recently identified nuclear receptor (NR) coactivator, interacts with beta-catenin. The N-terminus of GAC63 is the binding site for beta-catenin, whereas a C-terminal fragment of beta catenin including armadillo repeats 10-12 binds to GAC63. Over-expression of GAC63 enhanced the transcriptional activity of beta-catenin, and also greatly enhanced TCF/LEF-regulated reporter gene activity in a beta-catenin-dependent manner. Endogenous GAC63 was recruited to TCF/LEF-responsive enhancer elements when beta-catenin levels were induced by LiCl. In addition, reduction of endogenous GAC63 level by small interfering RNA (siRNA) inhibited TCF/LEF mediated gene transcription. Our findings reveal a new function of GAC63 in transcriptional activation of Wnt-responsive genes. PMID- 17344319 TI - Array-based profiling of reference-independent methylation status (aPRIMES) identifies frequent promoter methylation and consecutive downregulation of ZIC2 in pediatric medulloblastoma. AB - Existing microarray-based approaches for screening of DNA methylation are hampered by a number of shortcomings, such as the introduction of bias by DNA copy-number imbalances in the test genome and negligence of tissue-specific methylation patterns. We developed a method designated array-based profiling of reference-independent methylation status (aPRIMES) that allows the detection of direct methylation status rather than relative methylation. Array-PRIMES is based on the differential restriction and competitive hybridization of methylated and unmethylated DNA by methylation-specific and methylation-sensitive restriction enzymes, respectively. We demonstrate the accuracy of aPRIMES in detecting the methylation status of CpG islands for different states of methylation. Application of aPRIMES to the DNA from desmoplastic medulloblastomas of monozygotic twins showed strikingly similar methylation profiles. Additional analysis of 18 sporadic medulloblastomas revealed an overall correlation between highly methylated tumors and poor clinical outcome and identified ZIC2 as a frequently methylated gene in pediatric medulloblastoma. PMID- 17344320 TI - Site-directed transposon integration in human cells. AB - The Sleeping Beauty (SB) transposon is a promising gene transfer vector that integrates nonspecifically into host cell genomes. Herein, we attempt to direct transposon integration into predetermined DNA sites by coupling a site-specific DNA-binding domain (DBD) to the SB transposase. We engineered fusion proteins comprised of a hyperactive SB transposase (HSB5) joined via a variable-length linker to either end of the polydactyl zinc-finger protein E2C, which binds a unique sequence on human chromosome 17. Although DBD linkage to the C-terminus of SB abolished activity in a human cell transposition assay, the N-terminal addition of the E2C or Gal4 DBD did not. Molecular analyses indicated that these DBD-SB fusion proteins retained DNA-binding specificity for their respective substrate molecules and were capable of mediating bona fide transposition reactions. We also characterized transposon integrations in the presence of the E2C-SB fusion protein to determine its potential to target predefined DNA sites. Our results indicate that fusion protein-mediated tethering can effectively redirect transposon insertion site selection in human cells, but suggest that stable docking of integration complexes may also partially interfere with the cut and-paste mechanism. These findings illustrate the feasibility of directed transposon integration and highlight potential means for future development. PMID- 17344321 TI - Mg2+-dependent folding of a Diels-Alderase ribozyme probed by single-molecule FRET analysis. AB - Here, we report a single-molecule fluorescence resonance energy transfer (FRET) study of a Diels-Alderase (DAse) ribozyme, a 49-mer RNA with true catalytic properties. The DAse ribozyme was labeled with Cy3 and Cy5 as a FRET pair of dyes to observe intramolecular folding, which is a prerequisite for its recognition and turnover of two organic substrate molecules. FRET efficiency histograms and kinetic data were taken on a large number of surface-immobilized ribozyme molecules as a function of the Mg(2+) concentration in the buffer solution. From these data, three separate states of the DAse ribozyme can be distinguished, the unfolded (U), intermediate (I) and folded (F) states. A thermodynamic model was developed to quantitatively analyze the dependence of these states on the Mg(2+) concentration. The FRET data also provide information on structural properties. The I state shows a strongly cooperative compaction with increasing Mg(2+) concentration that arises from association with several Mg(2+) ions. This transition is followed by a second Mg(2+)-dependent cooperative transition to the F state. The observation of conformational heterogeneity and continuous fluctuations between the I and F states on the approximately 100 ms timescale offers insight into the folding dynamics of this ribozyme. PMID- 17344322 TI - Restriction endonuclease MvaI is a monomer that recognizes its target sequence asymmetrically. AB - Restriction endonuclease MvaI recognizes the sequence CC/WGG (W stands for A or T, '/' designates the cleavage site) and generates products with single nucleotide 5'-overhangs. The enzyme has been noted for its tolerance towards DNA modifications. Here, we report a biochemical characterization and crystal structures of MvaI in an apo-form and in a complex with target DNA at 1.5 A resolution. Our results show that MvaI is a monomer and recognizes its pseudosymmetric target sequence asymmetrically. The enzyme consists of two lobes. The catalytic lobe anchors the active site residues Glu36, Asp50, Glu55 and Lys57 and contacts the bases from the minor grove side. The recognition lobe mediates all major grove interactions with the bases. The enzyme in the crystal is bound to the strand with T at the center of the recognition sequence. The crystal structure with calcium ions and DNA mimics the prereactive state. MvaI shows structural similarities to BcnI, which cleaves the related sequence CC/SGG and to MutH enzyme, which is a component of the DNA repair machinery, and nicks one DNA strand instead of making a double-strand break. PMID- 17344323 TI - Are drug-eluting stents associated with a higher rate of late thrombosis than bare metal stents? Late stent thrombosis: a nuisance in both bare metal and drug eluting stents. PMID- 17344324 TI - Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. PMID- 17344325 TI - Comparison of intensive and low-dose atorvastatin therapy in the reduction of carotid intimal-medial thickness in patients with coronary heart disease. AB - BACKGROUND: Intensive statin therapy has been shown to improve prognosis in patients with coronary heart disease (CHD). It is unknown whether such benefit is mediated through the reduction of atherosclerotic plaque burden. AIM: To examine the efficacy of high-dose atorvastatin in the reduction of carotid intimal-medial thickness (IMT) and inflammatory markers in patients with CHD. DESIGN: Randomised trial. SETTING: Single centre. PATIENTS: 112 patients with angiographic evidence of CHD. INTERVENTIONS: A high dose (80 mg daily) or low dose (10 mg daily) of atorvastatin was given for 26 weeks. MAIN OUTCOME MEASURES: Carotid IMT, C reactive protein (CRP) and proinflammatory cytokine levels were assessed before and after therapy. RESULTS: The carotid IMT was reduced significantly in the high dose group (left: mean (SD), 1.24 (0.48) vs 1.15 (0.35) mm, p = 0.02; right: 1.12 (0.41) vs 1.01 (0.26) mm, p = 0.01), but was unchanged in the low-dose group (left: 1.25 (0.55) vs 1.20 (0.51) mm, p = NS; right: 1.18 (0.54) vs 1.15 (0.41) mm, p = NS). The CRP levels were reduced only in the high-dose group (from 3.92 (6.59) to 1.35 (1.83) mg/l, p = 0.01), but not in the low-dose group (from 2.25 (1.84) to 3.36 (6.15) mg/l, p = NS). A modest correlation was observed between the changes in carotid IMT and CRP (r = 0.21, p = 0.03). CONCLUSIONS: In patients with CHD, intensive atorvastatin therapy results in regression of carotid atherosclerotic disease, which is associated with reduction in CRP levels. On the other hand, a low-dose regimen only prevents progression of the disease. PMID- 17344326 TI - Measurement of left ventricular dyssynchrony in patients with ischaemic cardiomyopathy: a comparison of real-time three-dimensional and tissue Doppler echocardiography. AB - BACKGROUND: Real-time three-dimensional echocardiography (RT3DE) is an alternative modality to tissue Doppler imaging (TDI) for assessment of intraventricular dyssynchrony but its role is yet to be defined. OBJECTIVES: To (1) compare RT3DE and TDI for assessment of intraventricular dyssynchrony; (2) determine whether the two techniques agreed regarding the magnitude of dyssynchrony and identification of the site of maximal mechanical delay; and (3) investigate the reason for disagreement. PATIENTS: 100 patients with ischaemic cardiomyopathy. SETTING: Tertiary referral cardiac unit. MAIN OUTCOME MEASURES: Dispersion in time interval from QRS onset to peak sustained systolic tissue velocity by TDI (SD-T(TV)) and to minimal systolic volume by RT3DE (SD-T(3D)) between 12 ventricular segments. RESULTS: RT3DE image quality was adequate for measurement of SD-T3D in 77 (77%) patients. In the whole population, SD-T(TV) was 40 (20) ms and SD-T3D was 8.3% (3.4%). RT3DE identified a smaller proportion of patients as having significant dyssynchrony than TDI (49 (64%) patients vs 32 (42%) patients; p<0.01). The correlation between SD-T(TV) and SD-T3D was poor (r = 0.11, p = NS). There was concordance between TDI and RT3DE in identifying the site of maximal mechanical delay in 12 (16%) patients. Validating the two techniques with anatomical M-mode (AMM) as a parameter of radial timing revealed better agreement with RT3DE than with TDI (chi2 = 11.8, p = 0.001). CONCLUSION: In patients with ischaemic cardiomyopathy, TDI and RT3DE show poor agreement for evaluating the magnitude of intraventricular dyssynchrony and the site of maximal mechanical delay. This may partly relate to their respective assessment of longitudinal versus radial timing. PMID- 17344327 TI - Prediction of sudden death in patients with mild-to-moderate chronic heart failure by using cardiac iodine-123 metaiodobenzylguanidine imaging. AB - OBJECTIVE: To evaluate the usefulness of cardiac iodine-123 (123I) metaiodobenzylguanidine (MIBG) imaging as a predictor of sudden death in patients with chronic heart failure (CHF). DESIGN AND SETTING: Prospective cohort study in a tertiary referral centre. PATIENTS: 97 outpatients with CHF with a radionuclide left ventricular ejection fraction <40% (mean (SD) 29% (7.5%)). INTERVENTIONS: At study entry, cardiac I-123 MIBG imaging was performed. The cardiac MIBG heart-to mediastinum ratio (H/M) and washout rate (WR) were obtained from MIBG imaging. MAIN OUTCOME MEASURES: Patients were assigned to two groups based upon 27% of WR, which was the mean (2SD) control WR. 48 of 97 patients with CHF had abnormal WR (> or =27%), whereas the remaining 49 patients had normal WR (<27%). All the study patients were then followed up. RESULTS: During the mean (SD) follow-up period of 65 (29) months, 12 (25%) patients in the abnormal WR group and 2 (4%) patients in the normal WR group died suddenly. Kaplan-Meier analysis revealed that sudden death was more often observed in patients with abnormal WR than those with normal WR (p = 0.001). On Cox regression analysis, MIBG WR, H/M on the delayed image and H/M on the early image were significantly associated with sudden death. CONCLUSION: Cardiac MIBG imaging would be useful for predicting sudden death in patients with CHF. PMID- 17344328 TI - The delay of contrast arrival in magnetic resonance first-pass perfusion imaging: a novel non-invasive parameter detecting collateral-dependent myocardium. AB - AIM: To establish the regional delay of contrast arrival in magnetic resonance perfusion imaging (MRPI) for the detection of collateral-dependent myocardium in patients with coronary artery disease. DESIGN AND SETTING: Observational study, case series; single centre, university hospital. PATIENTS: 30 patients with coronary artery disease and collateral-dependent myocardium and 17 healthy volunteers. METHODS: Resting and hyperaemic (adenosine) MRPI was used to determine the delay time (Deltat(d)) of contrast arrival between the left ventricle and collateral-dependent or antegradely perfused myocardium, and myocardial perfusion (MP, ml/min/g). RESULTS: In healthy volunteers, mean (SD) Deltat(d) at rest and during hyperaemia were 0.8 (0.4) and 0.3 (0.3) s, and MP was 1.14 (0.21) and 4.23 (1.12) ml/min/g. In patients Deltat(d) in antegradely perfused vs collateral-dependent myocardium was 0.9 (0.7) vs 1.7 (1.0) s at rest (p<0.001), and 0.4 (0.3) vs 1.1 (0.6) s (p<0.001) during hyperaemia. MP was 1.12 (0.11) and 0.98 (0.28) ml/min/g (p = NS) at rest and 2.46 (0.85) vs 1.86 (0.91) ml/min/g (p<0.01) during hyperaemia. Receiver operating characteristics analysis showed the best sensitivity and specificity of 90% and 83% for hyperaemic Deltat(d) of >0.6 s (area under the curve (AUC) = 0.89) to detect collateral dependent myocardium, while resting Deltat(d) (AUC = 0.77) and perfusion (AUC = 0.69 at rest or 0.70 during hyperaemia) were less accurate. CONCLUSIONS: MRPI derived hyperaemic delay of contrast arrival detects collateral-dependent myocardium with high sensitivity and specificity. Perfusion was less sensitive, emphasising the clinical role of Deltat(d) in non-invasive detection of collateral-dependent myocardium. PMID- 17344329 TI - Failure to consult for symptoms of heart failure in patients with a type-D personality. AB - BACKGROUND: Self-management and adequate consultation behaviour are essential for the successful treatment of chronic heart failure (CHF). Patients with a type-D personality, characterised by high social inhibition and negative affectivity, may delay medical consultation despite increased symptom levels and may be at an increased risk for adverse clinical outcomes. AIM: To examine whether type-D personality predicts poor self-management and failure to consult for evident cardiac symptoms in patients with CHF. Design/methods/ PATIENTS: 178 outpatients with CHF (aged < or =80 years) completed the type-D Personality Scale at baseline, and the Health Complaints Scale (symptoms) and European Heart Failure Self-care Behaviour Scale (self-management) at 2 months of follow-up. Medical information was obtained from the patients' medical records. RESULTS: At follow up, patients with a type-D personality experienced more cardiac symptoms (OR 6.4; 95% CI 2.5 to 16.3, p<0.001) and more often appraised these symptoms as worrisome (OR 2.9; 95% CI 1.3 to 6.6, p<0.01) compared with patients with a non-type-D personality. Paradoxically, patients with a type-D personality were less likely to report these symptoms to their cardiologist/nurse, as indicated by an increased risk for inadequate consultation behaviour (OR 2.7; 95% CI 1.2 to 6.0, p<0.05), adjusting for demographics, CHF severity/aetiology, time since diagnosis and medication. Accordingly, of 61 patients with CHF who failed to consult for evident cardiac symptoms, 43% had a type-D personality (n = 26). Of the remaining 108 patients with CHF, only 14% (n = 16) had a type-D personality. CONCLUSION: Patients with CHF with a type-D personality display inadequate self-management. Failure to consult for increased symptom levels may partially explain the adverse effect of type-D personality on cardiac prognosis. PMID- 17344330 TI - Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen. AB - BACKGROUND: Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too many episodes of syncope to illicit drug use and thereby underestimate the incidence of TdP in this special population, and the high mortality in this population may, in part, be caused by the proarrhythmic effect of methadone. METHODS: In this cross sectional study interview, ECGs and blood samples were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 (approximately 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed about any experience of syncope. The association between opioid dose and QT, and methadone dose and reporting of syncope was assessed using multivariate linear regression and logistic regression, respectively. RESULTS: Methadone dose was associated with longer QT interval of 0.140 ms/mg (p = 0.002). No association between buprenorphine and QTc was found. Among the subjects treated with methadone, 28% men and 32% women had prolonged QTc interval. None of the subjects treated with buprenorphine had QTc interval >0.440 s((1/2)). A 50 mg higher methadone dose was associated with a 1.2 (95% CI 1.1 to 1.4) times higher odds for syncope. CONCLUSIONS: Methadone is associated with QT prolongation and higher reporting of syncope in a population of heroin addicts. PMID- 17344331 TI - The significance of circulating levels of both cardiac troponin I and high sensitivity C reactive protein for the prediction of intravenous thrombolysis outcome in patients with ST-segment elevation myocardial infarction. AB - OBJECTIVES: To evaluate, using continuous 12-lead ECG ST-segment monitoring, the role of circulating levels of both cardiac troponin I (cTnI) and high-sensitivity C reactive protein (hs-CRP), on presentation, in the prediction of intravenous thrombolysis outcome in patients with ST-segment elevation myocardial infarction (STEMI). DESIGN AND SETTING: Prospective observational study in a tertiary referral centre. PATIENTS: 786 consecutive patients with STEMI, who received intravenous thrombolysis in the first 6 h from index pain. MAIN OUTCOME MEASURES: The incidence of failed thrombolysis and of cardiac death by 30 days. Failed thrombolysis was defined as the absence of abrupt and sustained > or =50% ST segment recovery in the first 90 min after the initiation of intravenous thrombolysis. RESULTS: The incidence of failed thrombolysis and 30-day cardiac death was 57.4% and 11.8%, respectively. By multivariate logistic regression analysis according to tertiles of both cTnI (RR, 1.5; 95% CI 1.1 to 1.8, p = 0.004 for highest vs middle third; 2.2, 1.9 to 3.5, p<0.001 for highest vs lowest third; 1.5, 1.2 to 1.8, p = 0.001 for middle vs lowest third) and hs-CRP (RR, 2.0, 95% CI, 1.6 to 2.2; p<0.001 for highest vs middle third; 2.6, 2.1 to 3.5, p<0.001 for highest vs lowest third; 1.3, 1.2 to 1.7, p = 0.02 for middle vs lowest third), were independently associated with failed thrombolysis. Moreover, by multivariate Cox regression analysis according to tertiles of both cTnI (HR 1.2, 95% CI 1.1 to 1.8, p = 0.03 for highest vs middle third; 1.5, 1.2 to 2.2, p = 0.004 for highest vs lowest third; 1.1, 0.6 to 1.4, p = 0.6 for middle vs lowest third) and hs-CRP (HR1.2, 95% CI 1.1 to 1.6, p = 0.04 for highest vs middle third; 1.7, 1.3 to 2.6, p = 0.001 for highest vs lowest third; 1.1, 0.9 to 2.1, p = 0.1 for middle vs lowest third), were independently related with an increased risk of 30-day cardiac death. CONCLUSIONS: High circulating levels of both cTnI and hs-CRP are related with an independent increased risk of intravenous thrombolysis failure and 30-day cardiac death in patients who received intravenous thrombolysis in the first 6 h of STEMI. PMID- 17344332 TI - 64-Slice CT coronary angiography in patients with non-ST elevation acute coronary syndrome. AB - BACKGROUND: A high diagnostic accuracy of 64-slice CT coronary angiography (CTCA) has been reported in selected patients with stable angina pectoris, but only scant information is available in patients with non-ST elevation acute coronary syndrome (ACS). OBJECTIVES: To study the diagnostic performance of 64-slice CTCA in patients with non-ST elevation ACS. PATIENTS AND METHODS: 64-slice CTCA was performed in 104 patients (mean (SD) age 59 (9) years) with non-ST elevation ACS. Two independent, blinded observers assessed all coronary arteries for stenosis, using conventional quantitative angiography as a reference. Coronary lesions with >or=50% luminal narrowing were classified as significant. RESULTS: Conventional coronary angiography demonstrated the absence of significant disease in 15% (16/104) of patients, and the presence of single-vessel disease in 40% (42/104) and multivessel disease in 44% (46/104) of patients. Sensitivity for detecting significant coronary stenoses on a patient-by-patient analysis was 100% (88/88; 95% CI 95 to 100), specificity 75% (12/16; 95% CI 47 to 92), and positive and negative predictive values were 96% (88/92; 95% CI 89 to 99) and 100% (12/12; 95% CI 70 to 100), respectively. CONCLUSION: 64-slice CTCA has a high sensitivity to detect significant coronary stenoses, and is reliable to exclude the presence of significant coronary artery disease in patients who present with a non-ST elevation ACS. PMID- 17344333 TI - Inequalities in the primary care of patients with coronary heart disease and serious mental health problems: a cross-sectional study. AB - OBJECTIVE: To determine whether UK patients with coronary heart disease (CHD) who also have schizophrenia or bipolar disorder are less likely to receive primary care in accordance with the agreed national standards of the UK than patients without these mental health problems. DESIGN: Cross-sectional study. SETTING: 485 UK general practices contributing anonymised medical records of over 3.26 million patients to the QRESEARCH database. PARTICIPANTS: 127,932 patients with CHD of whom 701 had a diagnosis of schizophrenia or bipolar disorder. MAIN OUTCOME MEASURES: The relative risks of receiving statin medication and each of the CHD care indicators defined in the UK General Medical Services contract, for patients with schizophrenia or bipolar disorder compared with patients with neither condition. The results were adjusted for age, sex, deprivation, diabetes, stroke and smoking status, and allowed for clustering by practice. RESULTS: Patients with schizophrenia were 15% less likely to have a recent prescription for a statin (95% CI 8% to 20%) and 7% less likely to have a recent record of cholesterol level (95% CI 3% to 11%). There were no significant differences in the adjusted analyses between mental health groups on recording smoking status, advising on smoking cessation, recording blood pressure, achieving target blood pressure or cholesterol values, or prescribing aspirin, antiplatelets, anticoagulants or beta blockers. CONCLUSIONS: Although the majority of CHD care indicators are achieved equally for patients who also have a serious mental health problem, there is a shortfall in identifying and treating raised cholesterol among patients with schizophrenia, despite their higher level of risk factors. PMID- 17344334 TI - Statins in elderly patients with acute coronary syndrome: an analysis of dose and class effects in typical practice. AB - OBJECTIVE: To compare the effectiveness of statins of different treatment intensity used to treat elderly patients with acute coronary syndrome (ACS) in typical care settings. DESIGN: Retrospective cohort study using linked hospital and pharmacy claims data. SETTING: Statewide pharmacy benefits programmes in Pennsylvania and New Jersey. PARTICIPANTS: 18,311 Medicare patients discharged alive after ACS who received a prescription for a statin within 90 days of hospital discharge. MAIN OUTCOME MEASURES: Using multivariable and propensity matched Cox proportional hazards regression models, patients who were prescribed high-intensity and moderate-intensity statins were compared based on the drug dose combination that they initially received. Individual drug-dose combinations were also compared. Our primary outcome was the composite of all-cause death or recurrent ACS. RESULTS: Patients who received moderate-intensity statins were as likely to experience a primary outcome as patients treated with high-intensity statins (adjusted HR 1.02, 95% CI 0.96 to 1.08). Propensity matching did not change the results. Individually, all moderate-intensity statins were as effective as high-intensity atorvastatin with the exception of lovastatin (adjusted HR 1.22, 95% CI 1.09 to 1.36). Similarly, all high-intensity statins seem as effective as high-intensity atorvastatin but the CIs surrounding these estimates were wide. CONCLUSIONS: This analysis of elderly patients with ACS treated in typical care settings does not demonstrate the superiority of high intensity over moderate-intensity statin treatment or significant differences among individual statins. PMID- 17344335 TI - A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity. AB - Human carbonyl reductase 1 (CBR1) metabolizes endogenous and xenobiotic substrates such as the fever mediator, prostaglandin E2 (PGE2), and the anticancer anthracycline drug, daunorubicin. We screened 33 CBR1 full-length cDNA samples from white and black liver donors and performed database analyses to identify genetic determinants of CBR1 activity. We pinpointed a single nucleotide polymorphism on CBR1 (CBR1 V88I) that encodes for a valine-to-isoleucine substitution for further characterization. We detected the CBR1 V88I polymorphism in DNA samples from individuals with African ancestry (p = 0.986, q = 0.014). Kinetic studies revealed that the CBR1 V88 and CBR1 I88 isoforms have different maximal velocities for daunorubicin (V(max) CBR1 V88, 181 +/- 13 versus V(max) CBR1 I88, 121 +/- 12 nmol/min . mg, p < 0.05) and PGE2 (V(max) CBR1 V88, 53 +/- 7 versus V(max) CBR1 I88, 35 +/- 4 nmol/min . mg, p < 0.01). Concomitantly, CBR1 V88 produced higher levels of the cardiotoxic metabolite daunorubicinol compared with CBR1 I88 (1.7-fold, p < 0.0001). Inhibition studies demonstrated that CBR1 V88 and CBR1 I88 are distinctively inhibited by the flavonoid, rutin (IC50 CBR1 V88, 54.0 +/- 0.4 microM versus IC50 CBR1 I88, 15.0 +/- 0.1 microM, p < 0.001). Furthermore, isothermal titration calorimetry analyses together with molecular modeling studies showed that CBR1 V88I results in CBR1 isoforms with different binding affinities for the cofactor NADPH (K(d) CBR1 V88, 6.3 +/- 0.6 microM versus K(d) CBR1 I88, 3.8 +/- 0.5 microM). These studies characterize the first functional genetic determinant of CBR1 activity toward relevant physiological and pharmacological substrates. PMID- 17344336 TI - Induction of phase I and II drug metabolism in rat small intestine and colon in vitro. AB - The aim of this study was to evaluate drug metabolism in rat small intestinal and colon precision-cut slices during 24 h of incubation and the applicability of these slices for enzyme induction studies. Various parameters were evaluated: intracellular levels of ATP (general viability marker), alkaline phosphatase activity (specific epithelial marker), villin expression (specific epithelial marker), and metabolic rates of 7-ethoxycoumarin (CYP1A), testosterone (CYP3A and CYP2B), and 7-hydroxycoumarin (glucuronide and sulfate conjugation) conversions. ATP and villin remained constant up to, respectively, 5 and 8 h in small intestine and up to 24 h in colon. The metabolic rate remained constant in small intestinal slices up to 8 h and decreased afterward to 24 to 92%, depending on the substrate studied. The inducibility of metabolism in small intestinal and colon slices was tested with several inducers at various concentrations and incubation times. The following inducers were used: 3-methylcholanthrene, beta naphthoflavone, indirubin, and tert-butylhydroquinone (aryl hydrocarbon receptor ligands), dexamethasone (glucocorticoid receptor/pregnane X receptor ligand) and phenobarbital (constitutive androstane receptor ligand). After incubation with inducers, metabolic rates were evaluated with 7-ethoxycoumarin and testosterone (phase I) and 7-hydroxycoumarin (phase II) as substrate. All inducers elevated the metabolic rates consistent with the available published in vivo induction data. Induction of enzyme activity was already detectable after 5 h (small intestine) and after 8 h (colon) for 3-methylcholanthrene and beta-naphthoflavone and was clearly detectable for all tested inducers after 24 h (up to 20-fold compared with noninduced controls). In conclusion, small intestinal and colon precision-cut slices are useful for metabolism and enzyme induction studies. PMID- 17344337 TI - Use of hepatocytes to assess the contribution of hepatic uptake to clearance in vivo. AB - The wealth of information that has emerged in recent years detailing the substrate specificity of hepatic transporters necessitates an investigation into their potential role in drug elimination. Therefore, an assay in which the loss of parent compound from the incubation medium into hepatocytes ("media loss" assay) was developed to assess the impact of hepatic uptake on unbound drug intrinsic clearance in vivo (CL(int ub in vivo)). Studies using conventional hepatocyte incubations for a subset of 36 AstraZeneca new chemical entities (NCEs) resulted in a poor projection of CL(int ub in vivo) (r2 = 0.25, p = 0.002, average fold error = 57). This significant underestimation of CL(int ub in vivo) suggested that metabolism was not the dominant clearance mechanism for the majority of compounds examined. However, CL(int ub in vivo) was described well for this dataset using an initial compound "disappearance" CL(int) obtained from media loss assays (r2 = 0.72, p = 6.3 x 10(-11), average fold error = 3). Subsequent studies, using this method for the same 36 NCEs, suggested that the active uptake into human hepatocytes was generally slower (3-fold on average) than that observed with rat hepatocytes. The accurate prediction of human CL(int ub in vivo) (within 4-fold) for the marketed drug transporter substrates montelukast, bosentan, atorvastatin, and pravastatin confirmed further the utility of this assay. This work has described a simple method, amenable for use within a drug discovery setting, for predicting the in vivo clearance of drugs with significant hepatic uptake. PMID- 17344338 TI - Investigation of the metabolism and reductive activation of carcinogenic aristolochic acids in rats. AB - The metabolic activation of aristolochic acids (AAs) that have been demonstrated to be mutagenic and carcinogenic was investigated. In vitro metabolism study indicated that AAs were metabolized to N-hydroxyaristolactam, which could be either reduced to aristolactams or rearranged to 7-hydroxyaristolactams via the Bamberger rearrangement. In vivo metabolism study is important because the intermediates (aristolactam-nitriumion) of the nitroreduction process are thought to be responsible for the carcinogenicity of AAs. Liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (MS/MS) were applied to the analyses of a series of positional isomers of hydroxyaristolactams in rat urine samples after the in vivo study of AAs. Three hydroxylated metabolites of aristolactam II and two hydroxylated metabolites of aristolactam I were identified. The structures of the positional isomers were elucidated from the interpretation of MS/MS spectra and theoretical calculations. In addition, several new metabolites were detected in the rat urine by high-resolution mass spectrometry and MS/MS, including those from the decarboxylation of AAs and the conjugations of acetylation, glucuronidation, and sulfation of aristolochic acid Ia. PMID- 17344339 TI - Genotoxicity of 2-(3-chlorobenzyloxy)-6-(piperazinyl)pyrazine, a novel 5 hydroxytryptamine2c receptor agonist for the treatment of obesity: role of metabolic activation. AB - 2-(3-Chlorobenzyloxy)-6-(piperazin-1-yl)pyrazine (3) is a potent and selective 5 HT(2C) agonist that exhibits dose-dependent inhibition of food intake and reduction in body weight in rats, making it an attractive candidate for treatment of obesity. However, examination of the genotoxicity potential of 3 in the Salmonella Ames assay using tester strains TA98, TA100, TA1535, and TA1537 revealed a metabolism (rat S9/NADPH)- and dose-dependent increase of reverse mutations in strains TA100 and TA1537. The increase in reverse mutations was attenuated upon coincubation with methoxylamine and glutathione. The irreversible and concentration-dependent incorporation of radioactivity in calf thymus DNA after incubations with [14C]3 in the presence of rat S9/NADPH suggested that 3 was bioactivated to a reactive intermediate that covalently bound DNA. In vitro metabolism studies on 3 with rat S9/NADPH in the presence of methoxylamine and cyanide led to the detection of amine and cyano conjugates of 3. The mass spectrum of the amine conjugate was consistent with condensation of amine with an aldehyde metabolite derived from hydroxylation of the secondary piperazine nitrogen-alpha-carbon bond. The mass spectrum of the cyano conjugate suggested a bioactivation pathway involving N-hydroxylation of the secondary piperazine nitrogen followed by two-electron oxidation to generate an electrophilic nitrone, which reacted with cyanide. The 3-chlorobenzyl motif in 3 was also bioactivated via initial aromatic ring hydroxylation followed by elimination to a quinone methide species that reacted with glutathione or with the secondary piperazine ring nitrogen in 3 and its monohydroxylated metabolite(s). The metabolism studies described herein provide a mechanistic basis for the mutagenicity of 3. PMID- 17344340 TI - Molecular mechanism of basal CYP3A4 regulation by hepatocyte nuclear factor 4alpha: evidence for direct regulation in the intestine. AB - Cytochrome P450 3A4 plays an outstanding role in the metabolism of clinically used drugs and shows a marked interindividual variability in expression even in the absence of inducing agents. Thus, regulation of basal expression contributes considerably to variability. The nuclear receptor hepatocyte nuclear factor 4alpha (HNF4alpha) was previously shown to be associated with basal hepatic CYP3A4 expression. As how HNF4alpha regulates basal expression of CYP3A4 still remains elusive, we systematically screened 12.5 kilobase pairs (kb) of the CYP3A4 5' upstream region for activation by the receptor in the human intestinal cell line LS174T. In this study, we newly identified two widely separated regions mediating the activation by HNF4alpha: a far distal region at -9.0 kb and the proximal promoter region at approximately -0.2 kb. By gel shift experiments and transient transfections, we characterized direct repeat (DR) 1-type motifs in both regions as functional HNF4alpha response elements. Cooperation of the two regions was shown to be required for maximal activation by HNF4alpha. The effect of HNF4alpha was antagonized by chicken ovalbumin upstream promoter transcription factor II, which was shown to bind to one of the DR1 motifs. Furthermore, activation of CYP3A4 via the DR1 element in the proximal promoter depends on an additional, yet unknown, factor, which is binding at approximately -189 base pairs. Physiological relevance of this position for activation by HNF4alpha in vivo is suggested by the presence of a binding activity in small intestine similar to that in LS174T cells. In summary, we here have elucidated a molecular mechanism of direct regulation of CYP3A4 by HNF4alpha, which is probably specific for the intestine. PMID- 17344341 TI - Pharmacokinetics of ML3403 ({4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4 yl]-pyridin-2-yl}-(1-phenylethyl)-amine), a 4-Pyridinylimidazole-type p38 mitogen activated protein kinase inhibitor. AB - The p38 mitogen-activated protein kinase (MAPK) is a key mediator in cytokine induced signaling events that are activated in response to a variety of extracellular stimuli such as stress factors, apoptosis, and proliferation. Therefore, the MAPK family plays an integral role in disease states including oncogenesis, autoimmune diseases, and inflammatory processes. Inhibition of these protein kinases represents an attractive strategy for therapeutic intervention. In particular, one class of p38 MAP kinase inhibitors, the pyridinyl imidazole derivatives, is intensely investigated by several industrial groups, but so far no studies concerning the metabolism of these structurally related substances seem to be available. The objective of our examinations was the preclinical characterization of ML3403, {4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4 yl]-pyridin-2-yl}-(1-phenylethyl)-amine, a potent inhibitor of p38 MAP kinase, comprising the basic pyridinyl imidazole structure. In human hepatic microsomal incubations, the sulfoxidation to ML3603 ({4-[5-(4-fluorophenyl)-2-methylsulfinyl 3H-imidazol-4-yl]-pyridin-2-yl}-(1-phenylethyl)-amine) and M-sulfone ({4-[5-(4 fluorophenyl)-2-methylsulfonyl-3H-imidazol-4-yl]-pyridin-2-yl}-(1-phenylethyl) amine) was found to be the predominant metabolic transformation. In addition, oxidative removal of the phenylethyl moiety, pyridine N-oxidation, and hydroxylation reactions were observed. Incubations were carried out with hepatic microsomes from various species and with recombinant human cytochrome P450 isoenzymes, showing that CYP1A2, CYP2C19, CYP2D6, and CYP3A4 are the prominent enzymes in the metabolism of ML3403. Michaelis-Menten kinetics of ML3603 formation by these recombinant isoenzymes showed that CYP3A4 plays a pivotal role in the sulfoxidation reaction. In addition, pharmacokinetics of ML3403 were evaluated in male and female Wistar rats after oral gavage, showing a fast and high conversion to its active sulfoxide metabolite ML3603. A remarkable gender specific difference in the systemic exposure to ML3403 and ML3603 was found in rats. No gender-specific difference was detected in incubations with human liver microsomes. PMID- 17344342 TI - Humoral immune response after primary rubella virus infection and after vaccination. AB - We measured rubella virus immunoglobulin G (IgG) and IgM levels, as well as IgG avidity indexes, in serum samples taken before or after 6 months either after infection or after vaccination. The results obtained indicate that humoral immune responses are different after primary infection and after vaccination. This may have important consequences on the serological diagnosis of rubella virus infection. PMID- 17344343 TI - Use of serum or buffer-changed EDTA-plasma in a rapid, inexpensive, and easy-to perform hemolytic complement assay for differential diagnosis of systemic lupus erythematosus and monitoring of patients with the disease. AB - We previously described a simplified quantitative hemolytic assay for classical pathway (CP) hemolytic function in serum that has been shown to correlate with the 50% hemolytic complement (CH50) assay. In the present study, we used this assay to compare CP functions; plasma levels of C3, C4, and C3dg; and ratios of C3dg to C3 in healthy individuals and patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) with different degrees of complement activation. A significant depression in CP function and levels of C4 and C3 and increased C3dg levels and C3dg/C3 ratios were observed in the SLE patients. In patients with RA, CP function was normal, whereas C3, C4, and C3dg levels and the C3dg/C3 ratio were elevated. The SLE results are compatible with systemic complement consumption, whereas the RA data suggest an acute-phase reaction with a normal C3 catabolic rate. To facilitate the handling of patient samples, we also developed a method to restore the hemolytic function of EDTA-plasma by transferring it to Veronal-buffered saline containing the thrombin inhibitor lepirudin. This process inhibits coagulation and enables complement activation, allowing a longer time lag between sample harvesting and testing. These results, combined with previous correlation studies, suggest that the CP hemolytic assay can effectively replace the CH50 assay for routine SLE differential diagnosis and monitoring of disease activity. PMID- 17344344 TI - Inadequacy of colominic acid as an absorbent intended to facilitate use of complement-preserved baby rabbit serum in the Neisseria meningitidis serogroup B serum bactericidal antibody assay. AB - The surrogate of protection against Neisseria meningitidis serogroup B (MenB) is the serum bactericidal antibody (SBA) assay, which measures the functional activity of antibody by using an exogenous complement source. Despite baby rabbit complement having been used in meningococcal serogroup A, C, Y, and W135 SBA assays, it is not recommended for use in the MenB SBA assay due to elevated SBA titers caused by low-avidity anti-MenB capsular antibody in test sera. Therefore, the possibility of absorbing anti-MenB capsular antibody from test sera to enable the use of baby rabbit complement in the MenB SBA assay was investigated by comparing the results with those gained using human complement. Colominic acid from Escherichia coli K1, which shares the same linkage residue as MenB polysaccharide, was used as an absorbent due to the commercial unavailability of purified MenB polysaccharide. Inclusion of soluble colominic acid as an absorbent with baby rabbit complement resulted in a general reduction in SBA titers compared with those obtained using baby rabbit complement alone. However, these were not comparable to human SBA titers for all samples. Further optimization and investigations demonstrated that for some samples, colominic acid reduced titers to less than those achieved with human complement, and for others, it was not possible to inhibit titers by using colominic acid. The results suggested that the use of colominic acid will not result in the ability to use baby rabbit complement in the MenB SBA assay, thus not alleviating the difficulties in procuring human complement. However, alternative absorbents, such as purified MenB polysaccharide, may warrant further evaluation. PMID- 17344345 TI - Detection of H5 avian influenza viruses by antigen-capture enzyme-linked immunosorbent assay using H5-specific monoclonal antibody. AB - The unprecedented spread of highly pathogenic avian influenza virus subtype H5N1 in Asia and Europe is threatening animals and public health systems. Effective diagnosis and control management are needed to control the disease. To this end, we developed a panel of monoclonal antibodies (MAbs) against the H5N1 avian influenza virus (AIV) and implemented an antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) to detect the H5 viral antigen. Mice immunized with denatured hemagglutinin (HA) from A/goose/Guangdong/97 (H5N1) expressed in bacteria or immunized with concentrated H5N2 virus yielded a panel of hybridomas secreting MAbs specific for influenza virus HA. The reactivity of each MAb with several subtypes of influenza virus revealed that hybridomas 3D4 and 8B6 specifically recognized H5 HA. Therefore, purified antibodies from hybridomas 3D4 and 8B6, which secrete immunoglobulin G (IgG) and IgM, respectively, were used as the capture antibodies and pooled hyperimmune guinea pig serum IgG served as the detector antibody. The specificity of the optimized AC-ELISA was evaluated by using AIV subtypes H5 H3, H4, H7, H9, and H10. Specimens containing AIV subtype H5 subtype yielded a specific and strong signal above the background, whereas specimens containing all other subtypes yielded background signals. The detection limits of the AC-ELISA were 62.5 ng of bacterium-expressed H5N1 HA1 protein and 124, 62, and 31 50% tissue culture infective doses of influenza virus subtypes H5N1/PR8, H5N2, and H5N3, respectively. Reconstituted clinical samples consisting of H5 AIVs mixed with pharyngeal-tracheal mucus from healthy chickens also yielded positive signals in the AC-ELISA, and the results were confirmed by reverse transcription-PCR. The tracheal swab samples from H9N2-infected chickens did not give positive signals. Taken together, the newly developed MAb-based AC ELISA offers an attractive alternative to other diagnostic approaches for the specific detection of H5 AIV. PMID- 17344346 TI - Borreliacidal OspC antibody response of canines with Lyme disease differs significantly from that of humans with Lyme disease. AB - Humans reliably produce high concentrations of borreliacidal OspC antibodies specific for the seven C-terminal amino acids shortly after infection with Borrelia burgdorferi. We show that dogs also produce OspC borreliacidal antibodies but that their frequencies, intensities, and antigenicities differ significantly. The findings therefore confirm a major difference between the borreliacidal antibody responses of humans and canines with Lyme disease. PMID- 17344347 TI - Social mixing with other children during infancy enhances antibody response to a pneumococcal conjugate vaccine in early childhood. AB - Children who have siblings and/or who attend day care have higher rates of nasopharyngeal colonization with pneumococci than lone children do. Pneumococcal colonization is usually asymptomatic but is a prerequisite for invasive disease. We studied the effect of social mixing with other children on immunity to a pneumococcal vaccine. One hundred sixty children aged 1 year were immunized with a 7-valent conjugate pneumococcal vaccine. A blood sample was obtained before and 9 to 11 days after the vaccine. The concentration and avidity of antibody against vaccine pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) were studied in relation to pneumococcal carriage rate and measures of social mixing. Children with increased social mixing had higher antibody concentrations against serotypes 4, 9V, 14, and 23F than lone children did. The least-carried serotype, serotype 4, was the one of the most immunogenic. This contrasts with serotype 6B, the most common nasopharyngeal isolate but the least immunogenic. Social mixing in infancy enhances the immune response to a Streptococcus pneumoniae polysaccharide-protein conjugate vaccine at 1 year of age. Exposure to pneumococci in the first year of life may induce immunological priming. An alternative explanation is that differences in immunological experience, such as increased exposure to respiratory viral infections in early childhood, alters the response to vaccines perhaps by affecting the balance between Th1 and Th2 cytokines. The low immunogenicity of serotype 6B polysaccharide might make conditions more favorable for carriage of the 6B organism and explain why 6B pneumococci were more frequently isolated than other serotypes. PMID- 17344348 TI - Development of a simple latex agglutination assay for detection of shiga toxin producing Escherichia coli (STEC) by using polyclonal antibody against STEC. AB - Rabbit antiserum raised against the whole-cell antigen of Shiga toxin-producing Escherichia coli (STEC) strain VT3 (stx1+ stx2+ eae+) was repeatedly adsorbed with heat-killed cells of different non-STEC strains and other enteric bacteria. Thus, the antiserum obtained was designated VT3 antiserum. VT3 antiserum reacted with intimin type gamma. We assessed the reactivity of VT3 antiserum to whole cell lysates of 87 strains of E. coli and other enteric bacteria by immunoblotting. The antiserum recognized the 97-kDa protein in whole-cell lysate from strain VT3, and 36 (83.7%) of the 43 STEC strains were positive for the STEC antigen. None of the non-STEC strains or strains of other species examined tested positive by immunoblotting. Based on this result, we developed a latex agglutination assay for the detection of STEC strains. Thirty-five (81.4%) of the 43 STEC strains tested positive for the STEC antigen by the latex agglutination assay. One (3.3%) of the 30 non-STEC strains and none of the strains of the other enteric bacteria included in this study tested positive by the latex agglutination assay. The corresponding specificity of the latex agglutination assay was approximately 98%. Results of this study showed the production of STEC antiserum and the generation of a simple, cost-effective, sensitive, and specific latex agglutination assay for establishing an etiological diagnosis of STEC. PMID- 17344349 TI - Immune modulator adamantylamide dipeptide stimulates efficient major histocompatibility complex class I-restricted responses in mice. AB - Adamantylamide L-alanyl-D-isoglutamine (AdDP) is a synthetic adjuvant which belongs to the family of the desmuramyl peptides. AdDP exerts its adjuvant properties when it is administered either by the parenteral or by the mucosal route, leading to the elicitation of strong humoral responses at both the systemic and the mucosal levels. However, very little is known about the effect of AdDP on cellular immunity. Here we demonstrate that AdDP is able to stimulate cellular responses, which are characterized by the release of gamma interferon by CD8+ T cells when they are restimulated with a major histocompatibility complex class I-restricted peptide and strong in vivo lymphocyte-mediated cytotoxic activity. The capacity of AdDP to stimulate the elicitation of both cellular and humoral adaptive responses makes this adjuvant a promising tool for the development of mucosal vaccine formulations. PMID- 17344350 TI - Development and characterization of monoclonal antibodies and aptamers against major antigens of Mycobacterium avium subsp. paratuberculosis. AB - Specific antibodies, available in unlimited quantities, have not been produced against Mycobacterium avium subsp. paratuberculosis, the bacterium that causes Johne's disease (JD). To fill this gap in JD research, monoclonal antibodies (MAbs) against M. avium subsp. paratuberculosis were produced from BALB/c mice immunized with a whole-cell extract of M. avium subsp. paratuberculosis. A total of 10 hybridomas producing MAbs to proteins ranging from 25 to 85 kDa were obtained. All MAbs showed some degree of cross-reactivity when they were analyzed against a panel of whole-cell protein lysates comprising seven different mycobacterial species. The MAbs were characterized by several methods, which included isotype analysis, specificity analysis, epitope analysis, reactivity in immunoblot assays, and electron microscopy. The identities of the antigens that bound to two selected MAbs were determined by screening an M. avium subsp. paratuberculosis lambda phage expression library. This approach revealed that MAb 9G10 detects MAP1643 (isocitrate lyase) and that MAb 11G4 detects MAP3840 (a 70 kDa heat shock protein), two proteins present in high relative abundance in M. avium subsp. paratuberculosis. The epitopes for MAb 11G4 were mapped to the N terminal half of MAP3840, whereas MAb 9G10 bound to the C-terminal half of MAP1643. Aptamers, nucleic acids that bind to specific protein sequences, against the hypothetical protein encoded by MAP0105c were also generated and tested for their binding to M. avium subsp. paratuberculosis as well as other mycobacteria. These detection reagents may be beneficial in many JD research applications. PMID- 17344351 TI - Maternal milk contains antimicrobial factors that protect young rabbits from enteropathogenic Escherichia coli infection. AB - Enteropathogenic Escherichia coli (EPEC) colibacillosis represents a major cause of lethal diarrhea in young children in developing countries. EPEC strains also infect numerous mammal species and represent a major economical problem in rabbit industry. Protection against this pathogen is a challenging goal both in humans and in other mammal species. Despite a good knowledge of the pathogenicity mechanisms of EPEC, the intrinsic and environmental factors that control the expression of EPEC virulence in mammals remain unknown. For instance, the exacerbated sensitivity of young mammals to EPEC infection is still unexplained. Our goal was to investigate if age or other factors, like milk consumption, could be determinants that trigger the disease. We used rabbits as an animal model to study the role of milk in the sensitivity to an EPEC infection. Weaned and suckling rabbits were orally inoculated with EPEC strain E22 (O103:H2:K-) at 28 days of age, and the evolution of the disease was investigated in the two groups. In addition, in order to better characterize the interactions between milk and EPEC, we determined in vitro bacterial growth and the abilities of EPEC cells to adhere to epithelial cells in the presence of milk. Our results demonstrate a protective role of milk in vivo in association with in vitro antibacterial activity. These effects are independent of the presence of specific anti-EPEC antibodies. PMID- 17344352 TI - Histoplasmosis-associated cross-reactivity in the BioRad Platelia Aspergillus enzyme immunoassay. AB - We observed false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA) for specimens from patients with histoplasmosis and mice with experimental infection. Platelia Aspergillus EIA-positive specimens were negative in the second-generation Histoplasma antigen EIA. Care must be taken to exclude histoplasmosis for patients with positive Platelia Aspergillus EIA results. PMID- 17344354 TI - Involvement of MRP4 (ABCC4) in the luminal efflux of ceftizoxime and cefazolin in the kidney. AB - The purpose of the present study was to investigate the role of multidrug resistance-associated protein 4 (MRP4) in the tubular secretion of cephalosporin antibiotics. Most of the injectable cephalosporins have an inhibitory effect on the ATP-dependent uptake of [(3)H]dehydroepiandrosterone sulfate by membrane vesicles expressing hMRP4, whereas cephaloridine, cefsulodin, and cefepime do not. Aminocephalosporins have a weak inhibitory effect. Significant ATP-dependent transport of ceftizoxime (K(m), 18 microM), cefazolin (K(m), 80 microM), cefotaxime, and cefmetazole has been observed only in the membrane vesicles expressing hMRP4. Ceftizoxime and cefazolin were given by a constant intravenous infusion to wild-type and Mrp4(-/-) mice. The steady-state plasma concentrations of ceftizoxime and cefazolin were unchanged in Mrp4(-)(/)(-) mice. The urinary recovery of ceftizoxime was significantly reduced in Mrp4(-/-) mice, whereas it was unchanged for cefazolin. The kidney-to-plasma concentration ratio of ceftizoxime and cefazolin was increased 2.0- and 2.7-fold in Mrp4(-/-) mice, respectively; thus, the renal clearance with regard to the kidney concentration was reduced in Mrp4(-/-) mice, to 7.5 and 34% of the corresponding control values, respectively. These results suggest that Mrp4 is involved in the tubular secretion of ceftizoxime and cefazolin, in concert with basolateral uptake transporters. PMID- 17344353 TI - Involvement of a dysfunctional dopamine-D1/N-methyl-d-aspartate-NR1 and Ca2+/calmodulin-dependent protein kinase II pathway in the impairment of latent learning in a model of schizophrenia induced by phencyclidine. AB - Continuous ingestion of phencyclidine (PCP) in humans produces long-lasting schizophrenic-like cognitive dysfunction. Although a malfunction of dopaminergic and/or glutamatergic neurotransmission is implicated in the etiology of schizophrenia, involvement of the dopaminergic-glutamatergic neurotransmission in the cognitive dysfunction induced by repeated PCP treatment is minor. We demonstrated that mice treated with PCP (10 mg/kg/day s.c.) for 14 days displayed an impairment of latent learning in a water-finding task and of learning associated phosphorylation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and NR1 in the prefrontal cortex even after drug withdrawal. The infusion of a CaMKII inhibitor and NR1 antisense oligonucleotide into the prefrontal cortex produced an impairment of latent learning and decrease of learning-associated phosphorylation of CaMKII, which were observed in the PCP treated mice. Exogenous NMDA-induced CaMKII activation was not observed in slices of the prefrontal cortex prepared from mice treated repeatedly with PCP. The potentiation of NMDA receptor function by the infusion of glycine into the prefrontal cortex ameliorated these impairments in mice treated repeatedly with PCP. The high potassium-stimulated release of dopamine from the prefrontal cortex was less extensive in the PCP-treated than saline-treated mice. The infusion of a dopamine-D1 receptor agonist into the prefrontal cortex attenuated the impairment of latent learning and decrease of learning-associated NR1 phosphorylation in the PCP-treated mice, suggesting a functional linkage between glutamatergic and dopaminergic signaling. These findings indicate that repeated PCP treatment impairs latent learning through a prefrontal cortical dysfunction of NMDA-CaMKII signaling, which is associated with dopaminergic hypofunction. PMID- 17344355 TI - Corynebacterium accolens isolated from breast abscess: possible association with granulomatous mastitis. AB - Corynebacterium accolens is rarely isolated as a human pathogen. We describe here a case of C. accolens isolated from a breast abscess in a patient previously diagnosed with granulomatous mastitis. The possible association of Corynebacterium accolens and granulomatous mastitis in this patient is discussed. PMID- 17344356 TI - Molecular epidemiology of Staphylococcus saprophyticus isolated from women with uncomplicated community-acquired urinary tract infection. AB - Staphylococcus saprophyticus is a common cause of urinary tract infections (UTIs) in women. Little is known about the molecular epidemiology of S. saprophyticus UTIs. In the current study, we compared 76 isolates of S. saprophyticus prospectively isolated from women with uncomplicated UTI participating in a randomized placebo-controlled treatment trial performed in northern Sweden from 1995 to 1997 with 50 strains obtained in 2006 from five different locations in northern Europe with pulsed-field gel electrophoresis (PFGE). The aim was to elucidate the molecular epidemiology of this uropathogenic species and to investigate whether specific clones are associated with UTI in women. A total of 47 different PFGE profiles were detected among the 126 analyzed isolates. Ten clusters consisting of 5 to 12 isolates each showing PFGE DNA similarity of >85% were identified. Several clusters of genetically highly related isolates were detected in the original trial as well as among isolates obtained during 2006 from different locations. In the original trial, clonal persistence was found among 16 of 21 (76%) patients examined in the placebo group at follow-up 8 to 10 days after inclusion, indicating a low spontaneous short-time bacteriological cure rate. We conclude that multiple clones of S. saprophyticus were causing lower UTIs in women. The result suggests that some human-pathogenic clones of S. saprophyticus are spread over large geographical distances and that such clones may persist over long periods of time. PMID- 17344357 TI - Variability of properties of Vibrio parahaemolyticus strains isolated from individual patients. AB - Infections by strains belonging to the O3:K6 pandemic clone of Vibrio parahaemolyticus are prevalent in southern Thailand, and serovariants of these strains have also been detected. V. parahaemolyticus strains lacking important virulence genes (tdh and trh) were isolated from 6.5 to 10.9% of clinical specimens during the period from 2000 to 2003. In order to understand whether changes to the characteristics of V. parahaemolyticus occur during infection, 10 isolates collected from each of 63 patients who presented with diarrhea at the Hat Yai hospital from 2003 to 2004 were examined for the presence of the tdh and trh genes, the O:K serotype, and genetic markers for the pandemic clone. A total of 42 patients (66.7%) yielded identical isolates (homogeneous populations), and 21 of the patients (33.3%) yielded isolates that differed in at least one character from the other isolates (heterogeneous populations). The DNA fingerprints (examined by arbitrarily primed PCR and pulsed-field gel electrophoresis) of some, but not all, of the heterogeneous populations from single patients were indistinguishable. The results indicated that some patients were infected with a unique strain and that in vivo changes (tdh deletion or serotype conversion) might have occurred in certain individuals. It is therefore important to bear in mind that epidemiological studies based on the analysis of a single colony from a single patient might lead to misleading conclusions. Finally, the present study did not rule out the possibility that isolates lacking tdh and trh have unknown virulence mechanisms other than the tdh and trh genes. PMID- 17344358 TI - Variation in the number of tandem repeats and profile of surface protein genes among invasive group B Streptococci correlates with patient age. AB - The average number of tandem repeats of the rib gene (which encodes the Rib surface protein) in invasive group B streptococci from 29 neonates was smaller than that from 20 adults (6.8 and 8.6, respectively; P<0.05), implying a distinct contribution of immunity toward this age-related variation. PMID- 17344359 TI - Posaconazole treatment for Apophysomyces elegans rhino-orbital zygomycosis following trauma for a male with well-controlled diabetes. AB - We report a case of rhino-orbital zygomycosis in a 43-year-old male with well controlled diabetes mellitus. The patient initially received liposomal amphotericin B, but the infection continued to progress, so posaconazole treatment was begun and eventually led to the cure of his infection. The causative agent was identified as Apophysomyces elegans, an emerging cause of zygomycosis in immunocompetent hosts. PMID- 17344360 TI - Early identification of seronegative human immunodeficiency virus type 1 infection with severe presentation. AB - Specific antibodies against human immunodeficiency virus (HIV), usually used for diagnosis, almost invariably become detectable within 3 months of exposure. We report on a patient whose HIV infection was identified early by a combined antigen/antibody test, but seroconversion did not occur for 7 months, until the implementation of antiretroviral therapy. PMID- 17344361 TI - Comparison of the SPF10-LiPA system to the Hybrid Capture 2 Assay for detection of carcinogenic human papillomavirus genotypes among 5,683 young women in Guanacaste, Costa Rica. AB - The objective of this analysis was to compare the performance characteristics of two human papillomavirus (HPV) DNA detections assays, the Hybrid Capture 2 assay (HC2) and the SPF(10) assay, for the detection of carcinogenic HPV. Data are from the enrollment visits of women who participated in the randomized, double-blind, placebo-controlled phase III HPV16/18 Vaccine Trial in Guanacaste, Costa Rica. We compared the results of HC2 and SPF(10) testing of cervical specimens. Since the line probe assay (LiPA) detection system does not distinguish between HPV type 68 (HPV68; which is targeted by HC2) and HPV73 (which is not targeted by HC2), for SPF(10)-LiPA, we defined the carcinogenic HPV types as the 12 HC2-targeted types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), HPV68/73, and the HC2 cross-reactive, carcinogenic type HPV66. The kappa values and the performance characteristics for the detection of cervical abnormalities were ascertained. Paired observations were available for 5,683 sexually active, young women (median age, 21 years). The prevalence of carcinogenic HPV types was 35% (n=1,962) by HC2 and 35% (n=2,003) by SPF(10)-LiPA. There were no differences in the prevalence of carcinogenic HPV types by HC2 and SPF(10)-LiPA among women with normal, atypical squamous cells of undetermined significance and high-grade squamous intraepithelial lesion cytology. Among women with low-grade squamous intraepithelial lesion cytology, HC2 was more likely to test positive than SPF(10)-LiPA for the carcinogenic HPV types (87% and 79%, respectively; P=0.001) as a result of HC2 cross-reactivity with HPV types 40, 43, 44, 53, 54, 60, 70, and 74. The crude agreement between the two assays was 88%, with a kappa value of 0.75 (95% confidence limits, 0.73 to 0.76). We observed very good agreement between HC2 and SPF(10)-LiPA for carcinogenic HPV type detection. PMID- 17344362 TI - Genotypes and related factors reflecting macrolide resistance in pneumococcal pneumonia infections in Japan. AB - Although macrolide-resistant Streptococcus pneumoniae strains possessing either the ermB or mefA gene are very common in Japan, clinical and microbial factors in community-acquired pneumonia (CAP) caused by different macrolide resistance genotypes have not been evaluated. A multicenter study of CAP caused by S. pneumoniae was performed in Japan from 2003 to 2005. A total of 156 isolates were tested for susceptibility to antibiotics correlated with ermB and mefA genotyping. Independent relationships between tested variables and possession of either the ermB or the mefA gene were identified. Of 156 isolates, 127 (81.4%) were resistant to erythromycin, with the following distribution of resistance genotypes: ermB alone (50.0%), mefA alone (23.7%), and both ermB and mefA (7.1%). All isolates were susceptible to telithromycin. By multivariate analysis, oxygen saturation of <90% on admission increased the risk for ermB-positive pneumococcal pneumonia (odds ratio [OR]=11.1; 95% confidence interval [CI]=1.30 to 95.0; P=0.03), but there were no associations with mefA or with ermB mefA positivity. Penicillin nonsusceptibility was associated with mefA-positive and with ermB- and mefA-positive isolates (OR=14.2; 95% CI=4.27 to 46.9; P<0.0001 and P<0.0001, respectively) but not with ermB-positive isolates. The overall patient mortality was 5.1%. Mortality, the duration of hospitalization, and the resolution of several clinical markers were not associated with the different erythromycin resistance genotypes. In Japan, S. pneumoniae with erythromycin resistance or possession of ermB, mefA, or both genes was highly prevalent in patients with CAP. The risk factors for ermB-positive, mefA-positive, and double ermB-mefA positive pneumococcal pneumonia were different, but the clinical outcomes did not differ. PMID- 17344363 TI - Prevalence and characteristics of heteroresistant vancomycin-intermediate Staphylococcus aureus bacteremia in a tertiary care center. AB - Infections with S. aureus with heterogeneous intermediate resistance to vancomycin (hVISA) are occurring more frequently. The detection of these infections, their prevalence, clinical characteristics, and significance are controversial. During 2003 and 2004, all blood culture isolates of methicillin resistant Staphylococcus aureus (264 patients) at the Sheba Medical Center, Tel Hashomer, Israel, were assessed for hVISA by using the Etest macromethod. A total of 16 patients (6%) were positive for hVISA. Resistance to teicoplanin alone and to vancomycin alone using the Etest macromethod was found in 14 and 10 patients, respectively. Standard MICs to vancomycin were between 1 to 4 mg/ml. Most of these isolates (12 of 16 [75%]) would have been missed without specific testing. The median number of bacteremic days was 4. Seven patients had positive blood cultures for more than 5 days. Twelve patients died, and for eight of these the deaths were directly related to hVISA sepsis. We found that hVISA bacteremia was prevalent in our institution, and we suggest seeking hVISA in patients with persistent S. aureus bacteremia. PMID- 17344364 TI - Clostridium glycolicum bacteremia in a bone marrow transplant patient. AB - We describe a case of Clostridium glycolicum bacteremia and septic shock in an adult woman with a recent bone marrow transplant for relapsed Hodgkin's disease. The bacterium was identified by 16S rRNA gene sequencing. This is the first published report of the recovery of this organism from human clinical material. PMID- 17344366 TI - Evaluation of the AdvanDx VRE EVIGENE assay for detection of vanA in vancomycin resistant Staphylococcus aureus. AB - AdvanDx VRE EVIGENE, a commercial vanA/vanB DNA hybridization assay to identify vancomycin-resistant enterococci (VRE), was evaluated for the detection of vanA in Staphylococcus aureus. Performance was assessed using S. aureus, VRE, and vancomycin-intermediate and -susceptible isolates. The assay demonstrated 100% sensitivity and specificity when analyzed visually and by optical density. PMID- 17344365 TI - Characterization of the epidemic European fusidic acid-resistant impetigo clone of Staphylococcus aureus. AB - Resistance to the antibiotic fusidic acid in European strains of Staphylococcus aureus causing impetigo has increased in recent years. This increase appears to have resulted from clonal expansion of a strain we have designated the epidemic European fusidic acid-resistant impetigo clone (EEFIC), which carries the fusidic acid resistance determinant fusB on its chromosome. To understand better the properties of the EEFIC responsible for its success, we have performed detailed phenotypic and genotypic characterization of this clone. Molecular typing revealed the EEFIC to be ST123, spa type t171, and agr type IV and therefore unrelated to earlier prevalent fusB(+) strains found in the United Kingdom. EEFIC strains exhibited resistance to fusidic acid, penicillin, and, in some cases, erythromycin, which are all used in the treatment of impetigo. PCR analysis of the EEFIC and complete DNA sequencing of the 39.3 Kb plasmid it harbors identified genes encoding several toxins previously implicated in impetigo (exfoliative toxins A and B and EDIN-C). The location of fusB was mapped on the chromosome and found to be associated with a novel 16.6-kb genomic island integrated downstream of groEL. Although this element is related to classical staphylococcal pathogenicity islands, it does not encode any known virulence factors and consequently has been designated SaRI(fusB) (for "S. aureus resistance island carrying fusB"). PMID- 17344367 TI - Prevalence and significance of a negative extended-spectrum beta-lactamase (ESBL) confirmation test result after a positive ESBL screening test result for isolates of Escherichia coli and Klebsiella pneumoniae: results from the SENTRY Asia Pacific Surveillance Program. AB - A negative extended-spectrum beta-lactamase (ESBL) confirmation test result obtained after a positive ESBL screening test result using Clinical and Laboratory Standards Institute methods has been a common occurrence among isolates of Escherichia coli and Klebsiella pneumoniae in the SENTRY Antimicrobial Surveillance Program in the Asia-Pacific region. Among isolates collected between 1998 and 2004 this screen-positive, nonconfirmed profile (failed to show clavulanate synergy) was observed in 8.9% of 4,515 E. coli isolates and 20.3% of 2,303 K. pneumoniae isolates. We then selected 52 E. coli isolates and 68 K. pneumoniae isolates with a negative ESBL confirmation test, as well as comparable number of isolates with confirmed ESBL-positive tests, and examined them for the presence of TEM, SHV, plasmid-borne ampC, and CTX-M genes. We found that 62% of nonconfirming E. coli isolates and 75% of nonconfirming K. pneumoniae harbored a plasmid-borne AmpC enzyme of the CIT or DHA type. The majority of nonconfirming E. coli and K. pneumoniae from the Asia-Pacific region harbor important beta-lactamases, and a positive screening test alone should be sufficient grounds to report resistance to extended-spectrum cephalosporins in this region. PMID- 17344368 TI - Desynchronization of glutamate release prolongs synchronous CA3 network activity. AB - Periodic bursts of activity in the disinhibited in vitro hippocampal CA3 network spread through the neural population by the glutamatergic recurrent collateral axons that link CA3 pyramidal cells. It was previously proposed that these bursts of activity are terminated by exhaustion of releasable glutamate at the recurrent collateral synapses so that the next periodic burst of network activity cannot occur until the supply of glutamate has been replenished. As a test of this hypothesis, the rate of glutamate release at CA3 axon terminals was reduced by substitution of extracellular Ca(2+) with Sr(2+). Reduction of the rate of glutamate release reduces the rate of depletion and should thereby prolong bursts. Here we demonstrate that Sr(2+) substitution prolongs spontaneous bursts in the disinhibited adult CA3 hippocampal slices to 37.2 +/- 7.6 (SE) times the duration in control conditions. Sr(2+) also decreased the probability of burst initiation and the rate of burst onset, consistent with reduced synchrony of glutamate release and a consequent reduced rate of spread of excitation through the slice. These findings support the supply of releasable glutamate as an important determinant of the probability and duration of synchronous CA3 network activity. PMID- 17344369 TI - Illusions of force perception: the role of sensori-motor predictions, visual information, and motor errors. AB - Internal predictions influence the perception of force. When we support an object with one hand and lift it up with the other, we expect the force to disappear from the first, postural hand. In a virtual reality system, we violated this prediction by maintaining the force on the postural hand, whereas the object was still seen and felt to be lifted by the lifting hand. In this situation, participants perceived an illusionary increase in force on the postural hand, which was, in reality, constant. We test three possible mechanisms of how force perception may be influenced in this context. First, we showed that part of the illusion can be linked to a sensorimotor prediction--the predicted sensory consequences based on an efference copy of the lifting action. The illusion is reduced when the object is lifted by an external force. We also showed that the illusion changes on a trial-by-trial basis, paralleling the fast adaptation of the postural response. Second, motor errors that arise from a miscalibrated forward model do not contribute to the illusion; the illusion was unchanged even when we prevented motor errors by supporting the postural hand. Finally, visual information signaling the removal of the object is sufficient to elicit part of the illusion. These results argue that both sensorimotor predictions and visual object information, but not motor errors, influence force perception. PMID- 17344370 TI - Repetition suppression in monkey inferotemporal cortex: relation to behavioral priming. AB - In tasks requiring judgments about visual stimuli, humans exhibit repetition priming, responding with increased speed when a stimulus is repeated. Repetition priming might depend on repetition suppression, a phenomenon first observed in monkey inferotemporal cortex (IT) whereby, when a stimulus is repeated, the strength of the neuronal visual response is reduced. If the reduction resulted in sharpening of the cortical representation of the stimulus, and did not just scale it down, then speeded processing might result. To explore the relation between repetition priming and repetition suppression, we monitored neuronal activity in IT while monkeys performed a symmetry decision task. We found 1) that monkeys exhibit repetition priming, 2) that IT neurons simultaneously exhibit repetition suppression, 3) that repetition priming and repetition suppression do not vary in a significantly correlated fashion across trials, and 4) that repetition suppression scales down the representation of the stimulus without sharpening it. We conclude that repetition suppression accompanies repetition priming but is unlikely to be its cause. PMID- 17344372 TI - Riluzole-induced oscillations in spinal networks. AB - We previously showed in dissociated cultures of fetal rat spinal cord that disinhibition-induced bursting is based on intrinsic spiking, network recruitment, and a network refractory period after the bursts. A persistent sodium current (I(NaP)) underlies intrinsic spiking, which, by recurrent excitation, generates the bursting activity. Although full blockade of I(NaP) with riluzole disrupts such bursting, the present study shows that partial blockade of I(NaP) with low doses of riluzole maintains bursting activity with unchanged burst rate and burst duration. More important, low doses of riluzole turned bursts composed of persistent activity into bursts composed of oscillatory activity at around 5 Hz. In a search for the mechanisms underlying the generation of such intraburst oscillations, we found that activity-dependent synaptic depression was not changed with low doses of riluzole. On the other hand, low doses of riluzole strongly increased spike-frequency adaptation and led to early depolarization block when bursts were simulated by injecting long current pulses into single neurons in the absence of fast synaptic transmission. Phenytoin is another I(NaP) blocker. When applied in doses that reduced intrinsic activity by 80-90%, as did low doses of riluzole, it had no effect either on spike-frequency adaptation or on depolarization block. Nor did phenytoin induce intraburst oscillations after disinhibition. A theoretical model incorporating a depolarization block mechanism could reproduce the generation of intraburst oscillations at the network level. From these findings we conclude that riluzole induced intraburst oscillations are a network-driven phenomenon whose major accommodation mechanism is depolarization block arising from strong sodium channel inactivation. PMID- 17344371 TI - Muscarinic receptor activation elicits sustained, recurring depolarizations in reticulospinal neurons. AB - In lampreys, brain stem reticulospinal (RS) neurons constitute the main descending input to the spinal cord and activate the spinal locomotor central pattern generators. Cholinergic nicotinic inputs activate RS neurons, and consequently, induce locomotion. Cholinergic muscarinic agonists also induce locomotion when applied to the brain stem of birds. This study examined whether bath applications of muscarinic agonists could activate RS neurons and initiate motor output in lampreys. Bath applications of 25 microM muscarine elicited sustained, recurring depolarizations (mean duration of 5.0 +/- 0.5 s recurring with a mean period of 55.5 +/- 10.3 s) in intracellularly recorded rhombencephalic RS neurons. Calcium imaging experiments revealed that muscarine induced oscillations in calcium levels that occurred synchronously within the RS neuron population. Bath application of TTX abolished the muscarine effect, suggesting the sustained depolarizations in RS neurons are driven by other neurons. A series of lesion experiments suggested the caudal half of the rhombencephalon was necessary. Microinjections of muscarine (75 microM) or the muscarinic receptor (mAchR) antagonist atropine (1 mM) lateral to the rostral pole of the posterior rhombencephalic reticular nucleus induced or prevented, respectively, the muscarinic RS neuron response. Cells immunoreactive for muscarinic receptors were found in this region and could mediate this response. Bath application of glutamatergic antagonists (6-cyano-7-nitroquinoxaline-2,3 dione/D-2-amino-5-phosphonovaleric acid) abolished the muscarine effect, suggesting that glutamatergic transmission is needed for the effect. Ventral root recordings showed spinal motor output coincides with RS neuron sustained depolarizations. We propose that unilateral mAchR activation on specific cells in the caudal rhombencephalon activates a circuit that generates synchronous sustained, recurring depolarizations in bilateral populations of RS neurons. PMID- 17344373 TI - Eye position compensation improves estimates of response magnitude and receptive field geometry in alert monkeys. AB - Studies of visual function in behaving subjects require that stimuli be positioned reliably on the retina in the presence of eye movements. Fixational eye movements scatter stimuli about the retina, inflating estimates of receptive field dimensions, reducing estimates of peak responses, and blurring maps of receptive field subregions. Scleral search coils are frequently used to measure eye position, but their utility for correcting the effects of fixational eye movements on receptive field maps has been questioned. Using eye coils sutured to the sclera and preamplifiers configured to minimize cable artifacts, we reexamined this issue in two rhesus monkeys. During repeated fixation trials, the eye position signal was used to adjust the stimulus position, compensating for eye movements and correcting the stimulus position to place it at the desired location on the retina. Estimates of response magnitudes and receptive field characteristics in V1 and in LGN were obtained in both compensated and uncompensated conditions. Receptive fields were narrower, with steeper borders, and response amplitudes were higher when eye movement compensation was used. In sum, compensating for eye movements facilitated more precise definition of the receptive field. We also monitored horizontal vergence over long sequences of fixation trials and found the variability to be low, as expected for this precise behavior. Our results imply that eye coil signals can be highly accurate and useful for optimizing visual physiology when rigorous precautions are observed. PMID- 17344374 TI - Variability and corresponding amplitude-velocity relation of activity propagating in one-dimensional neural cultures. AB - We investigate the propagation of neural activity along one-dimensional rat hippocampal cultures patterned in lines over multielectrode arrays. Activity occurs spontaneously or is evoked by local electrical or chemical stimuli, with different resulting propagation velocities and firing rate amplitudes. A variability of an order of magnitude in velocity and amplitude is observed in spontaneous activity. A linear relation between velocity and amplitude is identified. We define a measure for neuron activation synchrony and find that it correlates with front velocity and is higher for electrically evoked fronts. We present a model that explains the linear relation between amplitude and velocity, which highlights the role of synchrony. The relation to current models for signal propagation in neural media is discussed. PMID- 17344375 TI - Cortical involvement in the generation of essential tremor. AB - Conflicting results on the existence of tremor-related cortical activity in essential tremor (ET) have raised questions on the role of the cortex in tremor generation. Here we attempt to address these issues. We recorded 64 channel surface EEGs and EMGs from forearm muscles in 15 patients with definite ET. EEG and EMG power spectra, relative power of the rhythmic EMG activity, relative EEG power at the tremor frequency, and EEG-EMG and EEG-EEG coherence were calculated and their dynamics over time explored. Corticomuscular delay was studied using a new method for narrow-band coherent signals. Corticomuscular coherence in the contralateral central region at the tremor frequency was present in all patients in recordings with a relative tremor EMG power exceeding a certain level. However, the coherence was lost intermittently even with tremors far above this level. Physiological 15- to 30-Hz coherence was found consistently in 11 patients with significantly weaker EMG activity in this frequency range. A more frontal (mesial) hot spot was also intermittently coupled with the tremor and the central hot spot in five patients. Corticomuscular delays were compatible with transmission in fast corticospinal pathways and feedback of the tremor signal. Thus the tremor rhythm is intermittently relayed only in different cortical motor areas. We hypothesize that tremor oscillations build up in different subcortical and subcortico-cortical circuits only temporarily entraining each other. PMID- 17344376 TI - Precise alignment of micromachined electrode arrays with V1 functional maps. AB - Recent theoretical models of primary visual cortex predict a relationship between receptive field properties and the location of the neuron within the orientation maps. Testing these predictions requires the development of new methods that allow the recording of single units at various locations across the orientation map. Here we present a novel technique for the precise alignment of functional maps and array recordings. Our strategy consists of first measuring the orientation maps in V1 using intrinsic optical imaging. A micromachined electrode array is subsequently implanted in the same patch of cortex for electrophysiological recordings, including the measurement of orientation tuning curves. The location of the array within the map is obtained by finding the position that maximizes the agreement between the preferred orientations measured electrically and optically. Experimental results of the alignment procedure from two implementations in monkey V1 are presented. The estimated accuracy of the procedure is evaluated using computer simulations. The methodology should prove useful in studying how signals from the local neighborhood of a neuron, thought to provide a dominant feedback signal, shape the receptive field properties in V1. PMID- 17344377 TI - Visual adaptation: physiology, mechanisms, and functional benefits. AB - Recent sensory experience affects both perception and the response properties of visual neurons. Here I review a rapid form of experience-dependent plasticity that follows adaptation, the presentation of a particular stimulus or ensemble of stimuli for periods ranging from tens of milliseconds to minutes. Adaptation has a rich history in psychophysics, where it is often used as a tool for dissecting the perceptual mechanisms of vision. Although we know comparatively little about the neurophysiological effects of adaptation, work in the last decade has revealed a rich repertoire of effects. This review focuses on this recent physiological work, the cellular and biophysical mechanisms that may underlie the observed effects, and the functional benefit that they may afford. I conclude with a brief discussion of some important open questions in the field. PMID- 17344378 TI - A novel effect of cochlear efferents: in vivo response enhancement does not require alpha9 cholinergic receptors. AB - Outer hair cells in the mammalian cochlea receive a cholinergic efferent innervation that constitutes the effector arm of a sound-evoked negative feedback loop. The well-studied suppressive effects of acetylcholine (ACh) release from efferent terminals are mediated by alpha9/alpha10 ACh receptors and are potently blocked by strychnine. Here, we report a novel, efferent-mediated enhancement of cochlear sound-evoked neural responses and otoacoustic emissions in mice. In controls, a slow enhancement of response amplitude to supranormal levels appears after recovery from the classic suppressive effects seen during a 70-s epoch of efferent shocks. The magnitude of post-shock enhancement can be as great as 10 dB and tends to be greater for high-frequency acoustic stimuli. Systemic strychnine at 10 mg/kg eliminates efferent-induced suppression, revealing a purely enhancing effect of efferent shocks, which peaks within 5 s after efferent-stimulation onset, maintains a constant level through the stimulation epoch, and slowly decays back to baseline with a time constant of approximately 100 s. In mice with targeted deletion of the alpha9 ACh receptor subunit, efferent-evoked effects resemble those in wild types with strychnine blockade, further showing that this novel efferent effect is fundamentally different from all cholinergic effects previously reported. PMID- 17344379 TI - In vitro properties of neurons in the rat pretectal nucleus of the optic tract. AB - The nucleus of the optic tract (NOT) has been implicated in the initiation of the optokinetic reflex (OKR) and in the modulation of visual activity during saccades. The present experiments demonstrate that these two functions are served by separate cell populations that can be distinguished by differences in both their cellular physiology and their efferent projections. We compared the response properties of NOT cells in rats using target-directed whole cell patch clamp recording in vitro. To identify the cells at the time of the recording experiments, they were prelabeled by retrograde axonal transport of WGA-apo-HRP gold (15 nm), which was injected into their primary projection targets, either the ipsilateral superior colliculus (iSC), or the contralateral NOT (cNOT), or the ipsilateral inferior olive (iIO). Retrograde labeling after injections in single animals of either WGA-apo-HRP-gold with different particle sizes (10 and 20 nm) or two different fluorescent dyes distinguished two NOT cell populations. One projects to both the iSC and cNOT. These cells are spontaneously active in vitro and respond to intracellular depolarizations with temporally regular tonic firing. The other population projects to the iIO and consists of cells that show no spontaneous activity, respond phasically to intracellular depolarization, and show irregular firing patterns. We propose that the spontaneously active pathway to iSC and cNOT is involved in modulating the level of visual activity during saccades and that the phasically active pathway to iIO provides a short-latency relay from the retina to premotor mechanisms involved in reducing retinal slip. PMID- 17344380 TI - Prime time for alpha-synuclein. PMID- 17344381 TI - Emergence of functional sensory subtypes as defined by transient receptor potential channel expression. AB - The existence of heterogeneous populations of dorsal root ganglion (DRG) neurons conveying different somatosensory information is the basis for the perception of touch, temperature, and pain. A differential expression of transient receptor potential (TRP) cation channels contributes to this functional heterogeneity. However, little is known about the development of functionally diverse neuronal subpopulations. Here, we use calcium imaging of acutely dissociated mouse sensory neurons and quantitative reverse transcription PCR to show that TRP cation channels emerge in waves, with the diversification of functional groups starting at embryonic day 12.5 (E12.5) and extending well into the postnatal life. Functional responses of voltage-gated calcium channels were present in DRG neurons at E11.5 and reached adult levels by E14.5. Responses to capsaicin, menthol, and cinnamaldehyde were first seen at E12.5, E16.5, and postnatal day 0 (P0), when the mRNA for TRP cation channel, subfamily V, member 1 (TRPV1), TRP cation channel, subfamily M, member 8 (TRPM8), and TRP cation channel, subfamily A, member 1 (TRPA1), respectively, was first detected. Cold-sensitive neurons were present before the expression or functional responses of TRPM8 or TRPA1. Our data support a lineage relationship in which TRPM8- and TRPA1-expressing sensory neurons derive from the population of TRPV1-expressing neurons. The TRPA1 subpopulation of neurons emerges independently in two distinct classes of nociceptors: around birth in the peptidergic population and after P14 in the nonpeptidergic class. This indicates that neurons with similar receptive properties can be generated in different sublineages at different developmental stages. This study describes for the first time the emergence of functional subtypes of sensory neurons, providing new insight into the development of nociception and thermoreception. PMID- 17344382 TI - Cell-autonomous TrkB signaling in presynaptic retinal ganglion cells mediates axon arbor growth and synapse maturation during the establishment of retinotectal synaptic connectivity. AB - BDNF contributes to the activity-dependent establishment and refinement of visual connectivity. In Xenopus, BDNF applications in the optic tectum influence retinal ganglion cell (RGC) axon branching and promote synapse formation and stabilization. The expression patterns of BDNF and TrkB suggest that BDNF specifically regulates the maturation of RGC axons at the target. It is possible, however, that BDNF modulates retinotectal synaptic connectivity by differentially influencing presynaptic RGC axons and postsynaptic tectal cells. Here, we combined single-cell expression of a dominant-negative TrkB-enhanced green fluorescent protein (GFP) fusion protein with confocal microscopy imaging in live Xenopus tadpoles to differentiate between presynaptic and postsynaptic actions of BDNF. Disruption of TrkB signaling in individual RGCs influenced the branching and synaptic maturation of presynaptic axon arbors. Specifically, GFP-TrkB.T1 overexpression increased the proportion of axons with immature, growth cone-like morphology, decreased axon branch stability, and increased axon arbor degeneration. In addition, GFP-TrkB.T1 overexpression reduced the number of red fluorescent protein-synaptobrevin-labeled presynaptic specializations per axon terminal. In contrast, overexpression of GFP-TrkB.T1 in tectal neurons did not alter synaptic number or the morphology or dynamic behavior of their dendritic arbors. Electron microscopy analysis revealed a significant decrease in the number of mature synaptic profiles and in the number of docked synaptic vesicles at retinotectal synapses made by RGC axons expressing GFP-TrkB.T1. Together, our results demonstrate that presynaptic TrkB signaling in RGCs is a key determinant in the establishment of visual connectivity and indicate that changes in tectal neuron synaptic connectivity are secondary to the BDNF-elicited enhanced stability and growth of presynaptic RGCs. PMID- 17344383 TI - Interaction of genetic and environmental factors in a Drosophila parkinsonism model. AB - Catastrophic loss of dopaminergic neurons is a hallmark of Parkinson's disease. Despite the recent identification of genes associated with familial parkinsonism, the etiology of most Parkinson's disease cases is not understood. Environmental toxins, such as the herbicide paraquat, appear to be risk factors, and it has been proposed that susceptibility is influenced by genetic background. The genetic model organism Drosophila is an advantageous system for the identification of genetic susceptibility factors. Genes that affect dopamine homeostasis are candidate susceptibility factors, because dopamine itself has been implicated in neuron damage. We find that paraquat can replicate a broad spectrum of parkinsonian behavioral symptoms in Drosophila that are associated with loss of specific subsets of dopaminergic neurons. In parallel with epidemiological studies that show an increased incidence of Parkinson's disease in males, male Drosophila exhibit paraquat symptoms earlier than females. We then tested the hypothesis that variation in dopamine-regulating genes, including those that regulate tetrahydrobiopterin, a requisite cofactor in dopamine synthesis, can alter susceptibility to paraquat-induced oxidative damage. Drosophila mutant strains that have increased or decreased dopamine and tetrahydrobiopterin production exhibit variation in susceptibility to paraquat. Surprisingly, protection against the neurotoxicity of paraquat is conferred by mutations that elevate dopamine pathway function, whereas mutations that diminish dopamine pools increase susceptibility. We also find that loss-of-function mutations in a negative regulator of dopamine production, Catecholamines-up, delay the onset of neurological symptoms, dopaminergic neuron death, and morbidity during paraquat exposure but confer sensitivity to hydrogen peroxide. PMID- 17344384 TI - Neurovascular coupling is not mediated by potassium siphoning from glial cells. AB - Neuronal activity evokes localized changes in blood flow, a response termed neurovascular coupling. One widely recognized hypothesis of neurovascular coupling holds that glial cell depolarization evoked by neuronal activity leads to the release of K+ onto blood vessels (K+ siphoning) and to vessel relaxation. We now present two direct tests of this glial cell-K+ siphoning hypothesis of neurovascular coupling. Potassium efflux was evoked from glial cells in the rat retina by applying depolarizing current pulses to individual cells. Glial depolarizations as large as 100 mV produced no change in the diameter of adjacent arterioles. We also monitored light-evoked vascular responses in Kir4.1 knock-out mice, where functional Kir K+ channels are absent from retinal glial cells. The magnitude of light-evoked vasodilations was identical in Kir4.1 knock-out and wild-type animals. Contrary to the hypothesis, the results demonstrate that glial K+ siphoning in the retina does not contribute significantly to neurovascular coupling. PMID- 17344385 TI - Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release. AB - Ca2+-dependent activator protein for secretion 2 (CAPS2/CADPS2) is a secretory granule-associated protein that is abundant at the parallel fiber terminals of granule cells in the mouse cerebellum and is involved in the release of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF), both of which are required for cerebellar development. The human homolog gene on chromosome 7 is located within susceptibility locus 1 of autism, a disease characterized by several cerebellar morphological abnormalities. Here we report that CAPS2 knock out mice are deficient in the release of NT-3 and BDNF, and they consequently exhibit suppressed phosphorylation of Trk receptors in the cerebellum; these mice exhibit pronounced impairments in cerebellar development and functions, including neuronal survival, differentiation and migration of postmitotic granule cells, dendritogenesis of Purkinje cells, lobulation between lobules VI and VII, structure and vesicular distribution of parallel fiber-Purkinje cell synapses, paired-pulse facilitation at parallel fiber-Purkinje cell synapses, rotarod motor coordination, and eye movement plasticity in optokinetic training. Increased granule cell death of the external granular layer was noted in lobules VI-VII and IX, in which high BDNF and NT-3 levels are specifically localized during cerebellar development. Therefore, the deficiency of CAPS2 indicates that CAPS2 mediated neurotrophin release is indispensable for normal cerebellar development and functions, including neuronal differentiation and survival, morphogenesis, synaptic function, and motor learning/control. The possible involvement of the CAPS2 gene in the cerebellar deficits of autistic patients is discussed. PMID- 17344386 TI - A conditional pan-neuronal Drosophila model of spinocerebellar ataxia 7 with a reversible adult phenotype suitable for identifying modifier genes. AB - Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the ataxin 7 (ATXN7) protein, a member of a multiprotein complex involved in histone acetylation. We have created a conditional Drosophila model of SCA7 in which expression of truncated ATXN7 (ATXN7T) with a pathogenic polyQ expansion is induced in neurons in adult flies. In this model, mutant ATXN7T accumulated in neuronal intranuclear inclusions containing ubiquitin, the 19S proteasome subunit, and HSP70 (heat shock protein 70), as in patients. Aggregation was accompanied by a decrease in locomotion and lifespan but limited neuronal death. Disaggregation of the inclusions, when expression of expanded ATXN7T was stopped, correlated with improved locomotor function and increased lifespan, suggesting that the pathology may respond to treatment. Lifespan was then used as a quantitative marker in a candidate gene approach to validate the interest of the model and to identify generic modulators of polyQ toxicity and specific modifiers of SCA7. Several molecular pathways identified in this focused screen (proteasome function, unfolded protein stress, caspase-dependent apoptosis, and histone acetylation) were further studied in primary neuronal cultures. Sodium butyrate, a histone deacetylase inhibitor, improved the survival time of the neurons. This model is therefore a powerful tool for studying SCA7 and for the development of potential therapies for polyQ diseases. PMID- 17344387 TI - Acquisition, extinction, and reacquisition of a cerebellar cortical memory trace. AB - Associative learning in the cerebellum underlies motor memories and probably also cognitive associations. Pavlovian eyeblink conditioning, a widely used experimental model of such learning, depends on the cerebellum, but the memory locus within the cerebellum as well as the underlying mechanisms have remained controversial. To date, crucial information on how cerebellar Purkinje cells change their activity during learning has been ambiguous and contradictory, and there is no information at all about how they behave during extinction and reacquisition. We have now tracked the activity of single Purkinje cells with microelectrodes for up to 16 h in decerebrate ferrets during learning, extinction, and relearning. We demonstrate that paired peripheral forelimb and periocular stimulation, as well as paired direct stimulation of cerebellar afferent pathways (mossy and climbing fibers) consistently causes a gradual acquisition of an inhibitory response in Purkinje cell simple spike firing. This conditioned cell response has several properties that matches known features of the behavioral conditioned response. The response latency varies with the interstimulus interval, and the response maximum is adaptively timed to precede the unconditioned stimulus. Across training trials, it matches behavioral extinction to unpaired stimulation and also the substantial savings that occur when paired stimulation is reinstated. These data suggest that many of the basic behavioral phenomena in eyeblink conditioning can be explained at the level of the single Purkinje cell. PMID- 17344388 TI - Activation of epidermal growth factor receptor inhibits KCNQ2/3 current through two distinct pathways: membrane PtdIns(4,5)P2 hydrolysis and channel phosphorylation. AB - KCNQ2/3 currents are the molecular basis of the neuronal M currents that play a critical role in neuron excitability. Many neurotransmitters modulate M/KCNQ currents through their G-protein-coupled receptors. Membrane PtdIns(4,5)P2 hydrolysis and channel phosphorylation are two mechanisms that have been proposed for modulation of KCNQ2/3 currents. In this study, we studied regulation of KCNQ2/3 currents by the epidermal growth factor (EGF) receptor, a member of another family of membrane receptors, receptor tyrosine kinases. We demonstrate here that EGF induces biphasic inhibition of KCNQ2/3 currents in human embryonic kidney 293 cells and in rat superior cervical ganglia neurons, an initial fast inhibition and a later slow inhibition. Additional studies indicate that the early and late inhibitions resulted from PtdIns(4,5)P2 hydrolysis and tyrosine phosphorylation, respectively. We further demonstrate that these two processes are mutually dependent. This study indicates that EGF is a potent modulator of M/KCNQ currents and provides a new dimension to the understanding of the modulation of these channels. PMID- 17344389 TI - Mice deficient in collapsin response mediator protein-1 exhibit impaired long term potentiation and impaired spatial learning and memory. AB - Collapsing response mediator protein-1 (CRMP-1) was initially identified in brain and has been implicated in plexin-dependent neuronal function. The high amino acid sequence identity among the five CRMPs has hindered determination of the functions of each individual CRMP. We generated viable and fertile CRMP-1 knock out (CRMP-1(-/-)) mice with no evidence of gross abnormality in the major organs. CRMP-1(-/-) mice exhibited intense microtubule-associated protein 2 (MAP2) staining in the proximal portion of the dendrites, but reduced and disorganized MAP2 staining in the distal dendrites of hippocampal CA1 pyramidal cells. Immunoreactivity to GAP-43 (growth-associated protein-43) and PSD95 (postsynaptic density-95) (a postsynaptic membrane adherent cytoskeletal protein) was also decreased in the CA1 region of the knock-out mice. These changes were consistent with the mutant mice showing a reduction in long-term potentiation (LTP) in the CA1 region and impaired performance in hippocampal-dependent spatial learning and memory tests. CRMP-1(-/-) mice showed a normal synapsin I labeling pattern in CA1 and normal paired-pulse facilitation. These findings provide the first evidence suggesting that CRMP-1 may be involved in proper neurite outgrowth in the adult hippocampus and that loss of CRMP-1 may affect LTP maintenance and spatial learning and memory. PMID- 17344390 TI - Statistical properties of pauses of the high-frequency discharge neurons in the external segment of the globus pallidus. AB - The neurons of many basal ganglia nuclei, including the external and internal globus pallidus (GPe and GPi, respectively) and the substantia nigra pars reticulata (SNr) are characterized by their high-frequency (50-100 spikes/s) tonic discharge (HFD). However, the high firing rate of GPe neurons is interrupted by long pauses. We studied the extracellularly recorded spiking activity of 212 well-isolated HFD GPe and 52 GPi/SNr neurons from five monkeys during different states of behavioral activity. An algorithm that maximizes the surprise function was used to detect pauses and pauser cells ("pausers"). Only 6% of the GPi/SNr neurons versus as many as 56% of the GPe neurons were classified as pausers. The GPe average pause duration equals 0.62 s. The interpause intervals follow a Poissonian distribution with a frequency of 13 pauses/minute. No linear relationship was found between pause parameters (duration or frequency) and the firing rate of the cell. Pauses were preceded by various changes in firing rate but not dominantly by a decrease. The average amplitude and duration of the spike waveform was modulated only after the pause but not before it. Pauses of pairs of cells that were recorded simultaneously were not correlated. The probability of GPe cells to pause spontaneously was extremely variable among monkeys (30-90%) and inversely related to the degree of the monkey's motor activity. These findings suggest that spontaneous GPe pauses are related to low arousal periods and are generated by a process that is independent of the discharge properties of the cells. PMID- 17344391 TI - PDP1epsilon functions downstream of the circadian oscillator to mediate behavioral rhythms. AB - The Drosophila circadian oscillator is composed of autoregulatory period/timeless (per/tim) and Clock (Clk) feedback loops that control rhythmic transcription. In the Clk loop, CLOCK-CYCLE heterodimers activate vrille (vri) and PAR domain protein 1epsilon (Pdp1epsilon) transcription, then sequential repression by VRI and activation by PDP1epsilon mediate rhythms in Clk transcription. Because VRI and PDP1epsilon bind the same regulatory element, the VRI/PDP1epsilon ratio is thought to control the level of Clk transcription. Thus, constant high or low PDP1epsilon levels in clock cells should eliminate Clk mRNA cycling and disrupt circadian oscillator function. Here we show that reducing PDP1epsilon levels in clock cells by approximately 70% via RNA interference or increasing PDP1epsilon levels by approximately 10-fold in clock cells does not alter Clk mRNA cycling or circadian oscillator function. However, constant low or high PDP1epsilon levels in clock cells disrupt locomotor activity rhythms despite persistent circadian oscillator function in brain pacemaker neurons that extend morphologically normal projections into the dorsal brain. These results demonstrate that the VRI/PDP1epsilon ratio neither controls Clk mRNA cycling nor circadian oscillator function and argue that PDP1epsilon is not essential for Clk activation. PDP1epsilon is nevertheless required for behavioral rhythmicity, which suggests that it functions to regulate oscillator output. PMID- 17344392 TI - Perceptual functions of perirhinal cortex in rats: zero-delay object recognition and simultaneous oddity discriminations. AB - The perirhinal cortex (PRh) is widely accepted as having an important role in object recognition memory in humans and animals. Contrary to claims that PRh mediates declarative memory exclusively, previous evidence suggests that PRh has a role in the perceptual processing of complex objects. In the present study, we conducted an examination of the possible role of PRh in perceptual function in rats. We examined whether bilateral excitotoxic lesions of PRh or PPRh (perirhinal plus postrhinal cortices) in the rat would cause deficits in a zero delay object-recognition task and a simultaneous oddity discrimination task. Both of these tasks measured spontaneous (untrained, unrewarded) behavior, and the stimuli in these experiments were manipulated to produce varying levels of perceptual difficulty. As predicted by simulations using a computational model, rats with PPRh lesions were impaired in object recognition when the stimuli to be discriminated were manipulated to share many features in common. Furthermore, rats with PPRh and PRh lesions were impaired in a simultaneous oddity discrimination task when the stimuli to be discriminated were manipulated explicitly to be more perceptually similar. These findings provide support for the idea that PRh in the rat is important for the perceptual processing of complex objects, in addition to its well established role in memory. PMID- 17344393 TI - Synaptic release generates a tonic GABA(A) receptor-mediated conductance that modulates burst precision in thalamic relay neurons. AB - Tonic inhibition has emerged as a key regulator of neuronal excitability in the CNS. Thalamic relay neurons of the dorsal lateral geniculate nucleus (dLGN) exhibit a tonic GABA(A) receptor (GABA(A)R)-mediated conductance that is correlated with delta-subunit expression. Indeed, consistent with the absence of delta-subunit expression, no tonic conductance is found in the adjacent ventral LGN. We show that, in contrast to the situation in cerebellar granule cells, thalamic delta-subunit-containing GABA(A)Rs (delta-GABA(A)Rs) do not contribute to a spillover component of IPSCs in dLGN. However, tonic activation of thalamic delta-GABA(A)Rs is sensitive to the global level of inhibition, showing an absolute requirement on the synaptic release of GABA. Thus, the tonic conductance is abolished when transmitter release probability is reduced or action potential evoked release is blocked. We further show that continuous activation of delta GABA(A)Rs introduces variability into the timing of low-threshold rebound bursts. Hence, activation of delta-GABA(A)Rs could act to destabilize thalamocortical oscillations and therefore have an important impact on behavioral state. PMID- 17344395 TI - Translation speed compensation in the dorsal aspect of the medial superior temporal area. AB - The dorsal aspect of the medial superior temporal area (MSTd) is involved in the computation of heading direction from the focus of expansion (FOE) of the visual image. Our laboratory previously found that MSTd neurons adjust their focus tuning curves to compensate for shifts in the FOE produced by eye rotation (Bradley et al., 1996) as well as for changes in pursuit speed (Shenoy et al., 2002). The translation speed of an observer also affects the shift of the FOE. To investigate whether MSTd neurons can adjust their focus tuning curves to compensate for varying translation speeds, we recorded extracellular responses from 93 focus-tuned MSTd neurons in two rhesus monkeys (Macaca mulatta) performing pursuit eye movements across displays of varying translation speeds. We found that MSTd neurons had larger shifts in their tuning curves for slow translation speeds and smaller shifts for fast translation speeds. These shifts aligned the focus tuning curves with the true heading direction and not with the retinal position of the FOE. Because the eye was pursuing at the same rate for varying translation speeds, these results indicate that retinal cues related both to translation speed and extraretinal signals from pursuit eye movements are used by MSTd neurons to compute heading direction. PMID- 17344394 TI - Sciatic nerve ligation-induced proliferation of spinal cord astrocytes is mediated by kappa opioid activation of p38 mitogen-activated protein kinase. AB - Partial sciatic nerve ligation (pSNL) markedly increased glial fibrillary acidic protein immunoreactivity (GFAP-IR) 1 week after lesion in the L4-L5 spinal dorsal horn of wild-type, but not in dynorphin knock-out, mice lacking kappa opioid receptors (KOR-/-) or in wild-type mice pretreated with the KOR antagonist nor binaltorphimine (norBNI). A direct effect of KOR on glial cell proliferation was suggested by the findings that primary cultures of type II GFAP-immunoreactive astrocytes isolated from mouse spinal cord express KOR. Sustained treatment with the kappa agonist U50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrolytinil) cyclohexyl]-benzeneacetamide methane sulfonate) significantly increased the proliferation rate of GFAP-immunoreactive astrocytes isolated from wild-type mice, and this effect was blocked by norBNI pretreatment. Proliferation of cultured type II astrocytes may have been stimulated by mitogen-activated protein kinase (MAPK) activation by KOR because (1) U50,488 treatment increased phospho p38 MAPK-immunoreactivity 247 +/- 44% over untreated cells, (2) the increase in phospho-p38 induced by U50,488 was blocked by norBNI and not evident in KOR-/- cultures, and (3) GFAP-immunoreactive astrocyte proliferation induced by U50,488 was blocked by the p38 MAPK inhibitor SB 203580 [4-(4-fluorophenyl)-2-(4 methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole]. Similar mechanisms of astrocyte activation may also be responsible in vivo because intrathecal injection of SB 203580 blocked the increased GFAP-IR in lumbar spinal cord induced by pSNL. Although the relationship between kappa-stimulated astrocyte proliferation and neuropathic pain mechanisms was not directly established in these studies, the results support the hypothesis that KOR activation induces spinal astrocyte proliferation, which may contribute to cellular reorganization after sciatic nerve damage. PMID- 17344396 TI - Maternal care modulates the relationship between prenatal risk and hippocampal volume in women but not in men. AB - Smaller hippocampal volume is associated with psychiatric disorders. Variations in hippocampal volume are discussed as both a consequence of the neurotoxic effects of stress and as a pre-existing condition leading to increased vulnerability for cognitive and emotional impairments. To investigate whether early experience can account for variability in hippocampal volume in adulthood (vulnerability hypothesis), we assessed the relationship between birth weight and hippocampal volume in 44 subjects. The reported quality of maternal care in early childhood, as evaluated by the Parental Bonding Inventory, was used as index of the quality of the postnatal environment. Hippocampal volume was assessed from magnetic resonance images using a manual segmentation protocol. We show that birth weight significantly predicts hippocampal volume in adulthood only in female subjects reporting low maternal care. The results suggest that the postnatal environment modulates the neurodevelopmental consequences of prenatal risk and that this effect is sex-specific. PMID- 17344397 TI - Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. AB - Here we report in vivo evidence of a neuroprotective role of proliferating microglial cells in cerebral ischemia. Using transgenic mice expressing a mutant thymidine kinase form of herpes simplex virus driven by myeloid-specific CD11b promoter and ganciclovir treatment as a tool, we selectively ablated proliferating (Mac-2 positive) microglia after transient middle cerebral artery occlusion. The series of experiments using green fluorescent protein-chimeric mice demonstrated that within the first 72 h after ischemic injury, the Mac-2 marker [unlike Iba1 (ionized calcium-binding adapter molecule 1)] was preferentially expressed by the resident microglia. Selective ablation of proliferating resident microglia was associated with a marked alteration in the temporal dynamics of proinflammatory cytokine expression, a significant increase in the size of infarction associated with a 2.7-fold increase in the number of apoptotic cells, predominantly neurons, and a 1.8-fold decrease in the levels of IGF-1. A double-immunofluorescence analysis revealed a approximately 100% colocalization between IGF-1 positive cells and Mac-2, a marker of activated/proliferating resident microglia. Conversely, stimulation of microglial proliferation after cerebral ischemia by M-CSF (macrophage colony stimulating factor) resulted in a 1.9-fold increase in IGF-1 levels and a significant increase of Mac2+ cells. Our findings suggest that a postischemic proliferation of the resident microglial cells may serve as an important modulator of a brain inflammatory response. More importantly, our results revealed a marked neuroprotective potential of proliferating microglia serving as an endogenous pool of neurotrophic molecules such as IGF-1, which may open new therapeutic avenues in the treatment of stroke and other neurological disorders. PMID- 17344398 TI - Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating alpha-tubulin. AB - Silent information regulator-2 (SIR2) proteins regulate lifespan of diverse organisms, but their distribution and roles in the CNS remain unclear. Here, we show that sirtuin 2 (SIRT2), a mammalian SIR2 homolog, is an oligodendroglial cytoplasmic protein and localized to the outer and juxtanodal loops in the myelin sheath. Among cytoplasmic proteins of OLN-93 oligodendrocytes, alpha-tubulin was the main substrate of SIRT2 deacetylase. In cultured primary oligodendrocyte precursors (OLPs), SIRT2 emergence accompanied elevated alpha-tubulin acetylation and OLP differentiation into the prematurity stage. Small interfering RNA knockdown of SIRT2 increased the alpha-tubulin acetylation, myelin basic protein expression, and cell arbor complexity of OLPs. SIRT2 overexpression had the opposite effects, and counteracted the cell arborization-promoting effect of overexpressed juxtanodin. SIRT2 mutation concomitantly reduced its deacetylase activity and its impeding effect on OLP arborization. These results demonstrated a counterbalancing role of SIRT2 against a facilitatory effect of tubulin acetylation on oligodendroglial differentiation. Selective SIRT2 availability to oligodendroglia may have important implications for myelinogenesis, myelin-axon interaction, and brain aging. PMID- 17344399 TI - Slack and Slick K(Na) channels regulate the accuracy of timing of auditory neurons. AB - The Slack (sequence like a calcium-activated K channel) and Slick (sequence like an intermediate conductance K channel) genes, which encode sodium-activated K+ (K(Na)) channels, are expressed at high levels in neurons of the medial nucleus of the trapezoid body (MNTB) in the auditory brainstem. These neurons lock their action potentials to incoming stimuli with a high degree of temporal precision. Channels with unitary properties similar to those of Slack and/or Slick channels, which are gated by [Na+]i and [Cl-]i and by changes in cytoplasmic ATP levels, are present in MNTB neurons. Manipulations of the level of K(Na) current in MNTB neurons, either by increasing levels of internal Na+ or by exposure to a pharmacological activator of Slack channels, significantly enhance the accuracy of timing of action potentials at high frequencies of stimulation. These findings suggest that such fidelity of timing at high frequencies may be attributed in part to high-conductance K(Na) channels. PMID- 17344400 TI - Oligomeric amyloid decreases basal levels of brain-derived neurotrophic factor (BDNF) mRNA via specific downregulation of BDNF transcripts IV and V in differentiated human neuroblastoma cells. AB - Alzheimer's disease (AD) is a senile dementia characterized by amyloid plaques, neurofibrillary tangles, and synaptic and cell loss. The "amyloid cascade" hypothesis suggests that amyloid-beta (Abeta), the peptide deposited as amyloid plaques, is the primary insult in AD. However, debate continues over the mechanism of Abeta toxicity and whether fibrillar or oligomeric Abeta is the active species of the peptide that ultimately causes the synaptic loss and dementia associated with AD. Brain-derived neurotrophic factor (BDNF) is required for survival and function of cells compromised in AD. Decreased BDNF causes defects in long-term potentiation and memory and correlates with cognitive decline. We previously demonstrated that BDNF reduction occurs early in the course of AD, suggesting that decreased BDNF may promote neuronal dysfunction in AD. We also demonstrated that three of seven human BDNF transcripts are specifically downregulated in AD. What pathological feature(s) of AD leads to the decreased BDNF is unknown. In this study, we administered both fibrillar and oligomeric conformations of Abeta(1-42) to differentiated SH-SY5Y, a human neuroblastoma cell line, and measured both phosphorylated cAMP response element binding protein (CREB), a regulator of BDNF transcription, and BDNF total mRNA. We found that oligomeric but not fibrillar preparations of Abeta(1-42) significantly decrease both phosphorylated CREB and total BDNF mRNA. Furthermore, oligomeric Abeta(1-42) decreases BDNF transcripts IV and V in these cells, demonstrating that Abeta(1-42) downregulates the major BDNF transcript decreased in vivo in the AD brain. Thus, oligomeric Abeta(1-42) could compromise neuronal function, causing memory loss and cognitive dysfunction by downregulation of BDNF in AD. PMID- 17344401 TI - Cellular basis for contrast gain control over the receptive field center of mammalian retinal ganglion cells. AB - Retinal ganglion cells fire spikes to an appropriate contrast presented over their receptive field center. These center responses undergo dynamic changes in sensitivity depending on the ongoing level of contrast, a process known as "contrast gain control." Extracellular recordings suggested that gain control is driven by a single wide-field mechanism, extending across the center and beyond, that depends on inhibitory interneurons: amacrine cells. However, recordings in salamander suggested that the excitatory bipolar cells, which drive the center, may themselves show gain control independently of amacrine cell mechanisms. Here, we tested in mammalian ganglion cells whether amacrine cells are critical for gain control over the receptive field center. We made extracellular and whole cell recordings of guinea pig Y-type cells in vitro and quantified the gain change between contrasts using a linear-nonlinear analysis. For spikes, tripling contrast reduced gain by approximately 40%. With spikes blocked, ganglion cells showed similar levels of gain control in membrane currents and voltages and under conditions of low and high calcium buffering: tripling contrast reduced gain by approximately 20-25%. Gain control persisted under voltage-clamp conditions that minimize inhibitory conductances and pharmacological conditions that block inhibitory neurotransmitter receptors. Gain control depended on adequate stimulation, not of ganglion cells but of presynaptic bipolar cells. Furthermore, horizontal cell measurements showed a lack of gain control in photoreceptor synaptic release. Thus, the mechanism for gain control over the ganglion cell receptive field center, as measured in the subthreshold response, originates in the presynaptic bipolar cells and does not require amacrine cell signaling. PMID- 17344402 TI - Microcircuitry for two types of achromatic ganglion cell in primate fovea. AB - Synaptic circuits in primate fovea have been quantified for midget/parvocellular ganglion cells. Here, based on partial reconstructions from serial electron micrographs, we quantify synaptic circuits for two other types of ganglion cell: the familiar parasol/magnocellular cell and a smaller type, termed "garland." The excitatory circuits both derive from two types of OFF diffuse cone bipolar cell, DB3 and DB2, which collected unselectively from at least 6 +/- 1 cones, including the S type. Cone contacts to DB3 dendrites were usually located between neighboring triads, whereas half of the cone contacts to DB2 were triad associated. Ribbon outputs were as follows: DB3, 69 +/- 5; DB2, 48 +/- 4. A complete parasol cell (30 microm dendritic field diameter) would collect from approximately 50 cones via approximately 120 bipolar and approximately 85 amacrine contacts; a complete garland cell (25 microm dendritic field) would collect from approximately 40 cones via approximately 75 bipolar and approximately 145 amacrine contacts. The bipolar types contributed differently: the parasol cell received most contacts (60%) from DB3, whereas the garland cell received most contacts (67%) from DB2. We hypothesize that DB3 is a transient bipolar cell and that DB2 is sustained. This would be consistent with their relative inputs to the brisk-transient (parasol) ganglion cell. The garland cell, with its high proportion of DB2 inputs plus its high proportion of amacrine synapses (70%) and dense mosaic, might correspond to the local-edge cell in nonprimate retinas, which serves finer acuity at low temporal frequencies. The convergence of S cones onto both types could contribute S-cone input for cortical areas primary visual cortex and the middle temporal area. PMID- 17344403 TI - Active beta-amyloid immunization restores spatial learning in PDAPP mice displaying very low levels of beta-amyloid. AB - The behavioral and biochemical impact of active immunization against human beta amyloid (Abeta) was assessed using male transgenic (Tg) mice overexpressing a human mutant amyloid precursor protein (heterozygous PDAPP mice) and littermate controls. Administration of aggregated Abeta42 occurred at monthly intervals from 7 months ("prevention") or 11 months ("reversal"), followed by double-blind behavioral training at 16 months on a cued task, then serial spatial learning in a water maze. Using a 2 x 2 design, with Abeta42 adjuvanted with MPL-AF (adjuvant formulation of monophosphoryl lipid A) or MPL-AF alone, PDAPP mice were impaired compared with non-Tg littermates on two separate measures of serial spatial learning. Immunization caused no overall rescue of learning but limited the accumulation of total Abeta and Abeta42 levels in cortex and hippocampus by up to 60%. In immunized PDAPP mice, significant negative correlations were observed between hippocampal and cortical Abeta levels and learning capacity, particularly in the prevention study, and correlations between learning capacity and antibody titer. Moreover, a subset of PDAPP mice with very low Abeta levels (hippocampal Abeta levels of <6000 ng/g or cortical Abeta levels of <1000 ng/g) was indistinguishable from non-Tg controls. Mice in the prevention study were also rescued from cognitive impairment more effectively than those in the reversal study. The combination of variability in antibody response and differential levels of Abeta accumulation across the population of immunized PDAPP mice may be responsible for success in cognitive protection with only a subset of these animals, but the similarity to the findings of certain human vaccination trials is noteworthy. PMID- 17344404 TI - Auditory cortical plasticity in learning to discriminate modulation rate. AB - The discrimination of temporal information in acoustic inputs is a crucial aspect of auditory perception, yet very few studies have focused on auditory perceptual learning of timing properties and associated plasticity in adult auditory cortex. Here, we trained participants on a temporal discrimination task. The main task used a base stimulus (four tones separated by intervals of 200 ms) that had to be distinguished from a target stimulus (four tones with intervals down to approximately 180 ms). We show that participants' auditory temporal sensitivity improves with a short amount of training (3 d, 1 h/d). Learning to discriminate temporal modulation rates was accompanied by a systematic amplitude increase of the early auditory evoked responses to trained stimuli, as measured by magnetoencephalography. Additionally, learning and auditory cortex plasticity partially generalized to interval discrimination but not to frequency discrimination. Auditory cortex plasticity associated with short-term perceptual learning was manifested as an enhancement of auditory cortical responses to trained acoustic features only in the trained task. Plasticity was also manifested as induced non-phase-locked high gamma-band power increases in inferior frontal cortex during performance in the trained task. Functional plasticity in auditory cortex is here interpreted as the product of bottom-up and top-down modulations. PMID- 17344405 TI - Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies. AB - Understanding the mechanisms whereby information encoded within patterns of action potentials is deciphered by neurons is central to cognitive psychology. The multiprotein complexes formed by NMDA receptors linked to synaptic membrane associated guanylate kinase (MAGUK) proteins including synapse-associated protein 102 (SAP102) and other associated proteins are instrumental in these processes. Although humans with mutations in SAP102 show mental retardation, the physiological and biochemical mechanisms involved are unknown. Using SAP102 knock out mice, we found specific impairments in synaptic plasticity induced by selective frequencies of stimulation that also required extracellular signal regulated kinase signaling. This was paralleled by inflexibility and impairment in spatial learning. Improvement in spatial learning performance occurred with extra training despite continued use of a suboptimal search strategy, and, in a separate nonspatial task, the mutants again deployed a different strategy. Double mutant analysis of postsynaptic density-95 and SAP102 mutants indicate overlapping and specific functions of the two MAGUKs. These in vivo data support the model that specific MAGUK proteins couple the NMDA receptor to distinct downstream signaling pathways. This provides a mechanism for discriminating patterns of synaptic activity that lead to long-lasting changes in synaptic strength as well as distinct aspects of cognition in the mammalian nervous system. PMID- 17344406 TI - Transmission of spike trains at the retinogeniculate synapse. AB - Retinal spikes impinging on relay neurons in the lateral geniculate nucleus (LGN) generate synaptic potentials, which sometimes produce spikes sent to visual cortex. We examined how signal transmission is regulated in the macaque LGN by recording the retinal input to a single LGN neuron while stimulating the receptive field center with a naturalistic luminance sequence. After extracting the EPSPs, which are often partially merged with spike waveforms, we found that >95% of spikes were associated with an EPSP from a single retinal ganglion cell. Each spike within a "burst" train was generated by an EPSP, indicating that LGN bursts are inherited from retinal bursts. LGN neurons rarely fired unless at least two EPSPs summated within 40 ms. This facilitation in EPSP efficacy was followed by depression. If a spike was generated by the first EPSP in a pair, it did not alter the efficacy of the second EPSP. Hence, the timing of EPSPs arising from the primary retinal driver governs synaptic efficacy and provides the basis for successful retinogeniculate transmission. PMID- 17344407 TI - Sensitization of calcitonin gene-related peptide receptors by receptor activity modifying protein-1 in the trigeminal ganglion. AB - The neuropeptide calcitonin gene-related peptide (CGRP) from the trigeminal ganglion has been established as a key player in the pathogenesis of migraine. In this study, we provide evidence that the responsiveness of neuronal CGRP receptors is strongly enhanced in vitro and in vivo by expression of human receptor activity-modifying protein-1 (hRAMP1), an obligatory subunit of the CGRP receptor. We first demonstrated that activation of CGRP receptors on cultured trigeminal ganglion neurons increased endogenous CGRP mRNA levels and promoter activity. The promoter activation was cAMP dependent and blocked by the antagonist BIBN4096BS [1-piperidinecarboxamide, N-[2-[[5-amino-l-[[4-(4 pyridinyl)-l-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4 hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)], a new antimigraine drug. Gene transfer using an adenoviral hRAMP1 expression vector increased the maximal production of cAMP by 1.8 +/- 0.2-fold and decreased the EC50 to 2.3 +/- 0.8 nM from 9.0 +/- 5.9 nM and 15.6 +/- 5.2 nM in uninfected and control-infected cultures, respectively. To establish whether RAMP1 is limiting in vivo as indicated from the culture studies, a transgenic mouse expressing hRAMP1 in the nervous system was generated. After CGRP injection into the whiskerpad, the hRAMP1 transgenic mice displayed 2.2 +/- 0.2-fold greater plasma extravasation, which is a measure of neurogenic inflammation. These results demonstrate that RAMP1 is functionally rate limiting for CGRP receptor activity in the trigeminal ganglion, which raises the possibility that elevated RAMP1 might sensitize some individuals to CGRP actions in migraine. PMID- 17344408 TI - Beta1 integrins control the formation of cell chains in the adult rostral migratory stream. AB - The subventricular zone (SVZ) of the lateral ventricle is the major site of neurogenesis in the adult brain. Neuroblasts that are born in the SVZ migrate as chains along the rostral migratory stream (RMS) to the olfactory bulb. Little is known about the mechanisms that control interactions between neuroblasts during their migration. Here we show that migrating neuroblasts express beta1 integrins and that the integrin ligand laminin is localized to cell chains. Using genetically modified mice and time-lapse video recordings of SVZ explants, we demonstrate that beta1 integrins and laminin promote the formation of cell chains. Laminin also induces the aggregation of purified neuroblasts. We conclude that the formation of cell chains in the RMS is controlled in part by beta1 integrins via binding to laminin. In addition, we provide evidence that beta1 class integrins are required for the maintenance of the glial tubes and that defects in the glial tubes lead to the ectopic migration of neuroblasts into the surrounding tissue. PMID- 17344409 TI - 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl imidazo[1,2-b]pyridazine: a novel brain-penetrant, orally available corticotropin releasing factor receptor 1 antagonist with efficacy in animal models of alcoholism. AB - We describe a novel corticotropin-releasing factor receptor 1 (CRF1) antagonist with advantageous properties for clinical development, and its in vivo activity in preclinical alcoholism models. 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1 ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP) inhibited 125I sauvagine binding to rat pituitary membranes and cloned human CRF1 with subnanomolar affinities, with no detectable activity at the CRF2 receptor or other common drug targets. After oral administration to rats, MTIP inhibited 125I sauvagine binding to rat cerebellar membranes ex vivo with an ED50 of approximately 1.3 mg/kg and an oral bioavailability of 91.1%. Compared with R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino pyrazolo[1,5-a]pyrimidine) and CP154526 (N-butyl-N-ethyl-4,9-dimethyl-7-(2,4,6 trimethylphenyl)-3,5,7-triazabicyclo[4.3.0]nona-2,4,8,10-tetraen-2-amine), MTIP had a markedly reduced volume of distribution and clearance. Neither open-field activity nor baseline exploration of an elevated plus-maze was affected by MTIP (1-10 mg/kg). In contrast, MTIP dose-dependently reversed anxiogenic effects of withdrawal from a 3 g/kg alcohol dose. Similarly, MTIP blocked excessive alcohol self-administration in Wistar rats with a history of dependence, and in a genetic model of high alcohol preference, the msP rat, at doses that had no effect in nondependent Wistar rats. Also, MTIP blocked reinstatement of stress-induced alcohol seeking both in postdependent and in genetically selected msP animals, again at doses that were ineffective in nondependent Wistar rats. Based on these findings, MTIP is a promising candidate for treatment of alcohol dependence. PMID- 17344411 TI - Microtubule-induced cortical cell polarity. AB - Most cells are polarized. Embryonic and stem cells can use their polarity to generate cell diversity by asymmetric cell division, whereas differentiated cells use their polarity to execute specific functions. For example, fibroblasts form an actin-rich leading edge required for cell migration, neurons form distinctive axonal and dendritic compartments important for directional signaling, and epithelial cells have apical and basolateral cortical domains necessary for maintaining tissue impermeability. It is well established that actin and actin associated proteins are essential for generating molecular and morphological cell polarity, but only recently has it become accepted that microtubules can induce and/or maintain polarity. One common feature among different cell types is that microtubules can establish the position of cortical polarity, but are not required for cortical polarity per se. In this review, we discuss how different cell types utilize microtubules and microtubule-associated signaling pathways to generate cortical cell polarity, highlight common mechanisms, and discuss open questions for directing future research. PMID- 17344412 TI - Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. AB - In eukaryotic cells, prereplication complexes (pre-RCs) are assembled on chromatin in the G1 phase, rendering origins of DNA replication competent to initiate DNA synthesis. When DNA replication commences in S phase, pre-RCs are disassembled, and multiple initiations from the same origin do not occur because new rounds of pre-RC assembly are inhibited. In most experimental organisms, multiple mechanisms that prevent pre-RC assembly have now been identified, and rereplication within the same cell cycle can be induced through defined perturbations of these mechanisms. This review summarizes the diverse array of inhibitory pathways used by different organisms to prevent pre-RC assembly, and focuses on the challenge of understanding how in any one cell type, various mechanisms cooperate to strictly enforce once per cell cycle regulation of DNA replication. PMID- 17344413 TI - Translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization by proteasome in yeast. AB - mRNA surveillance system represses the expression of nonstop mRNA by rapid mRNA degradation and translation repression. Here we show that the level of protein product of nonstop mRNA containing a poly(A) tail was reduced 100-fold, and this reduction was due to rapid mRNA degradation, translation repression, and protein destabilization, at least in part, by the proteasome. Insertion of a poly(A) tract upstream of a termination codon resulted in translation repression and protein destabilization, but not rapid mRNA decay. We propose that translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization. PMID- 17344414 TI - The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. AB - The p16INK4A and p14ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence, yet the mechanisms triggering their up regulation are not well understood. Here, we show that the ability of the oncogene BMI1 to repress the INK4A-ARF locus requires its direct association and is dependent on the continued presence of the EZH2-containing Polycomb-Repressive Complex 2 (PRC2) complex. Significantly, EZH2 is down-regulated in stressed and senescing populations of cells, coinciding with decreased levels of associated H3K27me3, displacement of BMI1, and activation of transcription. These results provide a model for how the INK4A-ARF locus is activated and how Polycombs contribute to cancer. PMID- 17344415 TI - A functional study of miR-124 in the developing neural tube. AB - Neural development is a highly orchestrated process that entails precise control of gene expression. Although microRNAs (miRNAs) have been implicated in fine tuning gene networks, the roles of individual miRNAs in vertebrate neural development have not been studied in vivo. We investigated the function of the most abundant neuronal miRNA, miR-124, during spinal cord development. Neither inhibition nor overexpression of miR-124 significantly altered the acquisition of neuronal fate, suggesting that miR-124 is unlikely to act as a primary determinant of neuronal differentiation. Two endogenous targets of miR-124, laminin gamma 1 and integrin beta1, were identified, both of which are highly expressed by neural progenitors but repressed upon neuronal differentiation. Thus miR-124 appears to ensure that progenitor genes are post-transcriptionally inhibited in neurons. PMID- 17344416 TI - Drosophila GAGA factor directs histone H3.3 replacement that prevents the heterochromatin spreading. AB - Epigenetic maintenance of the expression state of the genome is critical for development. Drosophila GAGA factor interacts with FACT and modulates chromatin structure for the maintenance of gene expression. Here we show that the GAGA factor-FACT complex and its binding site just downstream from the white gene are crucial for position effect variegation. Interestingly there is a dip of histone H3 Lys 9 methylation and a peak of H3 Lys 4 methylation at this site. The GAGA factor and FACT direct replacement of histone H3 by H3.3 through association of HIRA at this site, and maintain white expression under the heterochromatin environment. Based on these findings we propose that the GAGA factor and FACT dependent replacement of Lys 9-methylated histone H3 by H3.3 counteracts the spreading of silent chromatin. PMID- 17344417 TI - Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases. AB - Little is known about the regulation and function of the Notch1 gene in negative control of human tumors. Here we show that Notch1 gene expression and activity are substantially down-modulated in keratinocyte cancer cell lines and tumors, with expression of this gene being under p53 control in these cells. Genetic suppression of Notch signaling in primary human keratinocytes is sufficient, together with activated ras, to cause aggressive squamous cell carcinoma formation. Similar tumor-promoting effects are also caused by in vivo treatment of mice, grafted with keratinocytes expressing oncogenic ras alone, with a pharmacological inhibitor of endogenous Notch signaling. These effects are linked with a lesser commitment of keratinocytes to differentiation, an expansion of stem cell populations, and a mechanism involving up-regulation of ROCK1/2 and MRCKalpha kinases, two key effectors of small Rho GTPases previously implicated in neoplastic progression. Thus, the Notch1 gene is a p53 target with a role in human tumor suppression through negative regulation of Rho effectors. PMID- 17344418 TI - Dynamic regulation of miRNA expression in ordered stages of cellular development. AB - Short RNA expression in several distinct stages of T-lymphocyte development was comprehensively profiled. The total number of microRNAs (miRNAs) expressed per cell at different stages of development varies over nearly an order of magnitude in parallel with changes in total cellular RNA content, suggesting that global miRNA levels are coregulated with the translational capacity of the cell. However, individual miRNAs were dynamically regulated during T-cell development, with at least one miRNA or miRNA family overrepresented at each developmental stage. miRNA regulation in this developmental pathway is characterized by analog rather than switch-like behavior, with temporal enrichments at distinct stages of development observed against a background of constant, basal expression of the miRNA. Enrichments of these miRNAs are temporally correlated with depletions of the transcript levels of targets containing seed matches to the specific miRNAs, and may have specific functional consequences. miR-181a, which is specifically enriched at the CD4(+)CD8(+) (DP) stage of thymocyte development, can repress the expression of Bcl-2, CD69, and the T-cell receptor, all of which are coordinately involved in positive selection. PMID- 17344419 TI - New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis. AB - Acinetobacter baumannii has emerged as an important and problematic human pathogen as it is the causative agent of several types of infections including pneumonia, meningitis, septicemia, and urinary tract infections. We explored the pathogenic content of this harmful pathogen using a combination of DNA sequencing and insertional mutagenesis. The genome of this organism was sequenced using a strategy involving high-density pyrosequencing, a novel, rapid method of high throughput sequencing. Excluding the rDNA repeats, the assembled genome is 3,976,746 base pairs (bp) and has 3830 ORFs. A significant fraction of ORFs (17.2%) are located in 28 putative alien islands, indicating that the genome has acquired a large amount of foreign DNA. Consistent with its role in pathogenesis, a remarkable number of the islands (16) contain genes implicated in virulence, indicating the organism devotes a considerable portion of its genes to pathogenesis. The largest island contains elements homologous to the Legionella/Coxiella Type IV secretion apparatus. Type IV secretion systems have been demonstrated to be important for virulence in other organisms and thus are likely to help mediate pathogenesis of A. baumannii. Insertional mutagenesis generated avirulent isolates of A. baumannii and verified that six of the islands contain virulence genes, including two novel islands containing genes that lacked homology with others in the databases. The DNA sequencing approach described in this study allows the rapid elucidation of the DNA sequence of any microbe and, when combined with genetic screens, can identify many novel genes important for microbial pathogenesis. PMID- 17344420 TI - Cytosolic signaling protein Ecsit also localizes to mitochondria where it interacts with chaperone NDUFAF1 and functions in complex I assembly. AB - Ecsit is a cytosolic adaptor protein essential for inflammatory response and embryonic development via the Toll-like and BMP (bone morphogenetic protein) signal transduction pathways, respectively. Here, we demonstrate a mitochondrial function for Ecsit (an evolutionary conserved signaling intermediate in Toll pathways) in the assembly of mitochondrial complex I (NADH:ubiquinone oxidoreductase). An N-terminal targeting signal directs Ecsit to mitochondria, where it interacts with assembly chaperone NDUFAF1 in 500- to 850-kDa complexes as demonstrated by affinity purification and vice versa RNA interference (RNAi) knockdowns. In addition, Ecsit knockdown results in severely impaired complex I assembly and disturbed mitochondrial function. These findings support a function for Ecsit in the assembly or stability of mitochondrial complex I, possibly linking assembly of oxidative phosphorylation complexes to inflammatory response and embryonic development. PMID- 17344421 TI - Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study. AB - Reduced kidney function is a risk factor for cardiovascular morbidity and mortality, and both heart failure (HF) and kidney failure incidences are increasing. This study therefore sought to determine the effect of decreased kidney function on HF incidence in a population-based study of middle-aged adults. From 1987 through 2002, 14,857 participants of the Atherosclerosis Risk in Communities (ARIC) study who were free of prevalent HF at baseline were followed for incident HF hospitalization or death (International Classification of Diseases, Ninth Revision/10th Revision 428/I50). Estimated GFR (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) Study equation, and kidney function was categorized as normal (eGFR > or =90 ml/min per 1.73 m(2); n = 7143), mildly reduced (eGFR 60 to 89 ml/min per 1.73 m(2); n = 7311), and moderately/severely reduced (eGFR <60 ml/min per 1.73 m(2); n = 403). Cox proportional hazards models were used to control for demographic and cardiovascular risk factors; analyses were stratified by the presence of coronary heart disease at baseline. During a mean follow-up of 13.2 yr, 1193 participants developed HF. The incidence of HF was three-fold higher for individuals with eGFR <60 ml/min per 1.73 m(2) compared to the reference group with eGFR > or =90 ml/min per 1.73 m(2) (18 versus 6 per 1000 person-years). The overall adjusted relative hazard of developing HF was 1.94 (1.49 to 2.53) for individuals with eGFR <60 ml/min per 1.73 m(2) compared to the reference group and was significantly increased for individuals with and without prevalent coronary heart disease at baseline. A substantially greater decline in kidney function occurred in individuals concomitant with HF hospitalization/death compared to those who did not develop HF. In summary, middle-aged adults with moderately/severely reduced kidney function are at high risk for developing HF. PMID- 17344422 TI - The Bradykinin B2 receptor gene is a target of angiotensin II type 1 receptor signaling. AB - Cross-talk between G protein-coupled receptors (GPCR) is known to occur at multiple levels, including receptor heterodimerization and intracellular signaling. This study tested the hypothesis that GPCR cross-talk occurs at the transcriptional level. It was demonstrated that the bradykinin B2 receptor gene (BdkrB2) is a direct transcriptional target of the angiotensin II (AngII) type 1 receptor (AT(1)R) in collecting duct cells. AngII induced BdkrB2 mRNA expression in mouse inner medullary collecting duct cells, and this effect was abrogated by AT(1)R blockade; in contrast, AT(2)R blockade was ineffective. Actinomycin D, an inhibitor of gene transcription, abrogated AngII-stimulated BdkrB2 expression. In addition, AngII produced dosage- and time-dependent increases in B2 receptor protein levels (2.9 +/- 0.4 fold; P < 0.05). AngII stimulated phosphorylation of cAMP response element binding protein (CREB) on Ser-133 and assembly of p-CREB on the BdkrB2 promoter in vivo. Moreover, AngII induced hyperacetylation of BdkrB2 promoter-associated H4 histones, a chromatin modification that is associated with gene activation. Mutations of the CRE abrogated AngII-induced activation of the BdkrB2 promoter. AngII-treated inner medullary collecting duct cells exhibited augmented intracellular calcium signaling in response to bradykinin, confirming the functional relevance of AT(1)-B2 receptor signaling. Finally, studies that were conducted in angiotensin type 1 receptor (Agtr1)-null mice revealed that BdkrB2 mRNA levels were significantly lower in the renal medulla of Agtr1(A)(-/-) and Agtr1(A/B)(-/-) than in Agtr1(+/+) and Agtr1(B)(-/-) mice. It is concluded that BdkrB2 is a downstream target of the AT(1)R-CREB signaling pathway. Transcriptional regulation represents a novel form of cross-talk between GPCR that link the renin-angiotensin and kallikrein-kinin systems. PMID- 17344423 TI - Mouse podocyte complement factor H: the functional analog to human complement receptor 1. AB - Complement factor H (Cfh) is a key plasma protein in humans and animals that serves to limit alternative pathway complement activation in plasma, as well as in local sites such as capillaries of the glomerulus and eye. It was shown that rodent Cfh on platelets is the functional analogue to human erythrocyte complement receptor 1 with a role that is distinct from plasma Cfh and that Cfh is also on cultured rodent podocytes. For investigation of the role of Cfh in the kidney, renal transplants were performed between wild-type (WT) and Cfh(-/-) C57BL/6 mice. For these studies, bilateral native nephrectomies were done so that renal function was dependent solely on the transplanted kidney. Chronic serum sickness was induced by active immunization with apoferritin. Diffuse proliferative glomerulonephritis (GN) occurred in WT kidneys that were transplanted into Cfh(-/-) recipients (n = 8) but not into WT recipients (n = 14), consistent with the importance of plasma Cfh to dictate outcome in this disease model. Relative to the WT recipients of WT kidneys, WT mice with Cfh(-/-) kidneys (n = 12) developed glomerular disease features, including increased albuminuria (82.8 +/- 7.0 versus 45.1 +/- 3.6 microg/mg creatinine; P < 0.001) and blood urea nitrogen levels (54.4 +/- 6.1 versus 44.2 +/- 3.7 mg/dl; P < 0.01). In addition, they had substantial glomerular capillary wall deposits of IgG and C3, which by electron microscopy were present in subendothelial and subepithelial immune deposits, whereas WT kidneys in WT hosts had almost exclusive mesangial deposits. The IgG deposits in Cfh(-/-) kidneys were adjacent to Cfh-deficient podocytes, whereas WT kidneys in a Cfh(-/-) host had podocyte associated Cfh with absent IgG deposits. These data suggest that locally produced podocyte Cfh is important to process immune complexes in the subepithelial space, where it also limits complement activation. Just as in platelets, rodent podocytes seem to use Cfh as the functional surrogate for human complement receptor 1. PMID- 17344424 TI - Simvastatin prevents coronary microvascular remodeling in renovascular hypertensive pigs. AB - Patients with hypertension and chronic kidney disease are at risk for cardiovascular diseases, possibly related to inflammation. Statins have beneficial anti-inflammatory effects on vascular structure regardless of cholesterol reduction. It was hypothesized that alterations in myocardial microvascular structure in swine renovascular hypertension (RVH) would be improved by simvastatin treatment. Three groups of pigs were studied after 12 wk: normal (n = 7), RVH (n = 7), or RVH+simvastatin (RVH+S; 80 mg/d; n = 6). Left ventricular muscle mass and myocardial perfusion were determined in vivo using electron beam computed tomography, and myocardial samples then were scanned ex vivo using micro-computed tomography for measurement of the spatial density of myocardial microvessels (80 to 500 microm) in situ. Capillary density and myocardial expression of inflammatory and growth factors were determined in myocardial tissue. The effects of simvastatin on inflammation-induced tube formation were evaluated in vitro in human umbilical vein endothelial cells that were exposed to TNF-alpha. RVH and RVH+S had similarly increased arterial pressure and serum creatinine. However, left ventricular hypertrophy was prevented by simvastatin, and myocardial perfusion was increased. Compared with normal, RVH showed increased spatial density of microvessels (169.6 +/- 21 versus 107.7 +/- 15.2 vessels/cm(2); P < 0.05), which was decreased in RVH+S (72.5 +/- 14.9 vessels/cm(2)), whereas capillary density remained similar to normal. RVH also increased myocardial expression of inflammatory and growth factors, which were reversed by simvastatin. Furthermore, simvastatin attenuated TNF-alpha induced angiogenesis in vitro. Simvastatin prevents myocardial microvascular remodeling and hypertrophy in experimental RVH independent of lipid lowering. This protective effect is partly mediated by blunted expression as well as angiogenic activity of inflammatory cytokines. PMID- 17344425 TI - Prevalence and characteristics of a family history of end-stage renal disease among adults in the United States population: Reasons for Geographic and Racial Differences in Stroke (REGARDS) renal cohort study. AB - This report describes the prevalence and characteristics of people with a family history of ESRD in a first-degree relative (FH-ESRD). This is a cross-sectional study of individuals in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, a population-based sample of US residents who are 45 yr and older. FH-ESRD was ascertained at baseline among 12,030 participants of the cohort, and multivariate logistic regression was used to identify characteristics that were independently associated with FH-ESRD. FH-ESRD was reported by 9.5% of participants. Individual characteristics that were independently associated with FH-ESRD included black race (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.82 to 2.53); female gender (OR 1.28; 95% CI 1.08 to 1.51); a history of diabetes (OR 1.22; 95% CI 1.02 to 1.47); a 1-SD change in the log of the C reactive protein level (OR 1.10; 95% CI 1.01 to 1.19); and World Health Organization body mass index weight categories normal (OR 2.11; 95% CI 0.66 to 6.79), overweight (OR 2.64; 95% CI 0.82 to 8.42), and obese (OR 3.48; 95% CI 1.09 to 11.1) compared with underweight. Black but not white individuals with FH-ESRD were more likely to have an estimated GFR <60 ml/min per 1.73 m(2). There is a high prevalence of FH-ESRD among US adults, and the prevalence of FH-ESRD was higher among lack individuals. Individuals with a positive family history were more likely to have diabetes and to be obese. If confirmed, then these findings suggest that individuals with FH-ESRD may benefit from interventions to improve the detection and treatment of chronic kidney disease risk factors such as diabetes and obesity. PMID- 17344426 TI - Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation. AB - The mineralocorticoid hormone aldosterone controls sodium reabsorption and BP largely by regulating the cell-surface expression and function of the epithelial sodium channel (ENaC) in target kidney tubules. Part of the stimulatory effect of aldosterone on ENaC is mediated by the induction of serum- and glucocorticoid regulated kinase 1 (Sgk1), a kinase that interferes with the ubiquitylation of ENaC by ubiquitin-protein ligase Nedd4-2. In vivo early aldosterone-regulated mRNA now has been identified in microselected mouse distal nephron by microarray. From 22 mRNA that displayed a two-fold or more change, 13 were downregulated and nine were upregulated. Besides Sgk1, the induced mRNA include Grem2 (protein related to DAN and cerebrus [PRDC]), activating transcription factor 3, cAMP responsive element modulator, and the ubiquitin-specific protease Usp2-45. The induction of this last enzyme isoform was verified in mouse distal nephron tubule at the protein level. With the use of Hek293 cells, Xenopus oocytes, and mpkCCD(c14) cells as expression systems, it was shown that Usp2-45 deubiquitylates ENaC and stimulates ENaC-mediated sodium transport, an effect that is not additive to that of Sgk1. A deubiquitylating enzyme that targets ENaC in vitro and thus may play a role in sodium transport regulation was identified within a series of new in vivo early aldosterone-regulated gene products. PMID- 17344427 TI - Protective role of hypoxia-inducible factor-2alpha against ischemic damage and oxidative stress in the kidney. AB - Central to cellular responses to hypoxic environment is the hypoxia-inducible factor (HIF) transcriptional control system. A role for HIF-2alpha was investigated in a model of renal ischemia-reperfusion injury (IRI) associated with oxidative stress using HIF-2alpha knockdown mice. In these mice, HIF-2alpha expression was approximately one half that of wild-type mice, whereas HIF-1alpha expression was equivalent. HIF-2alpha knockdown mice were more susceptible to renal IRI, as indicated by elevated blood urea nitrogen levels and semiquantitative histologic analysis. Immunostaining with markers of oxidative stress showed enhanced oxidative stress in the kidney of HIF-2alpha knockdown mice, which was associated with peritubular capillary loss. Real-time quantitative PCR analysis showed decreased expression of antioxidative stress genes in the HIF-2alpha knockdown kidneys. Studies that used small interference RNA confirmed regulation of the antioxidative stress genes in cultured endothelial cells. Although HIF-2alpha knockdown mice were anemic, serum erythropoietin levels were not significantly increased, reflecting inappropriate response to anemia as a result of HIF-2alpha knockdown. Experiments that used hemodiluted mice with renal ischemia demonstrated that anemia of this degree did not affect susceptibility to ischemia. Knockdown of HIF-2alpha in inflammatory cells by bone marrow transplantation experiments demonstrated that HIF-2alpha in inflammatory cells did not contribute to susceptibility to renal IRI. Restoration of HIF-2alpha in endothelium by intercrossing with Tie1-Cre mice ameliorated renal injury by IRI, demonstrating a specific role of endothelial HIF-2alpha. These results suggest that HIF-2alpha in the endothelium has a protective role against ischemia of the kidney via amelioration of oxidative stress. PMID- 17344429 TI - Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer. AB - Protease-activated receptors (PARs) are G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. PARs play crucial roles in hemostasis and thrombosis, as well as in inflammation and vascular development. Coagulant proteases, which are generated at sites of vascular injury, act mainly through PARs to elicit signalling in a variety of cell types. Since PARs are irreversibly activated signalling must be tightly regulated. Desensitization and trafficking of proteolytically activated PARs control the magnitude, duration and spatial aspects of receptor signalling. Recent studies have revealed novel endocytic sorting mechanisms that regulate PAR signalling. PARs have also been implicated in tumor progression. PARs are overexpressed in several types of malignant cancer, transmit signals in response to tumor-generated proteases and promote tumor growth, invasion and metastasis. Recent work also indicates that matrix metalloprotease 1 (MMP-1) signals through PAR1 to promote tumor growth and invasion. In addition to PAR overexpression, tumor cells display aberrant PAR1 trafficking, which causes persistent signalling and cellular invasion. Thus, a novel type of gain-of-function in GPCR signalling in cancer can be acquired through dysregulation of receptor trafficking. PMID- 17344430 TI - Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19. AB - Kit ligand (Kitl), the ligand for the Kit receptor tyrosine kinase, plays important roles in hematopoiesis, gametogenesis and melanogenesis. Kitl is synthesized as a membrane-anchored precursor that can be processed to produce the soluble growth factor. Here, we evaluated the role of ADAM (a disintegrin and metalloprotease) metalloproteases in ectodomain shedding of Kitl. We found that both ADAM17 and ADAM19 affect Kitl1 shedding, albeit in different ways. Overexpression of ADAM19 resulted in decreased levels of Endo-H-resistant mature Kitl1, thereby reducing the amount of Kitl that is shed from cells following stimulation with phorbol esters. ADAM17 was identified as the major phorbol-ester stimulated sheddase of Kitl1, whereas ADAMs 8, 9, 10, 12 and 15 were not required for this process. ADAM17 also emerged as the major constitutive and phorbol-ester stimulated sheddase of Kitl2 in mouse embryonic fibroblasts. Mutagenesis of the juxtamembrane domain of Kitl2 showed no stringent sequence requirement for cleavage by ADAM17, although two nonadjacent stretches of four amino acid residues were identified that are required for Kitl2 shedding. Taken together, this study identifies a novel sheddase, ADAM17, for Kitl1 and Kitl2, and demonstrates that ADAM19 can reduce ADAM17-dependent phorbol-ester-stimulated Kitl1 ectodomain shedding. PMID- 17344431 TI - Initiation and resolution of interhomolog connections: crossover and non crossover sites along mouse synaptonemal complexes. AB - Programmed double-strand breaks at prophase of meiosis acquire immunologically detectable RAD51-DMC1 foci or early nodules (ENs) that are associated with developing chromosome core segments; each focus is surrounded by a gammaH2AX modified chromosome domain. The 250-300 ENs per nucleus decline in numbers during the development of full-length cores and the remaining foci are relatively evenly distributed along the mature cores (gamma distribution of nu=2.97). The ENs become transformed nodules (TNs) by the acquisition of RPA, BLM, MSH4 and topoisomerases that function in repair and Holliday junction resolution. At the leptotene-zygotene transition, TNs orient to positions between the aligned cores where they initiate structural interhomolog contacts prior to synaptonemal complex (SC) formation, possibly future crossover sites. Subsequently, TNs are associated with SC extension at the synaptic forks. Dephosphorylation of TN associated histone gammaH2AX chromatin suggests annealing of single strands or repair of double-strand breaks DSBs at this time. Some 200 TNs per pachytene nucleus are distributed proportional to SC length and are evenly distributed along the SCs (nu= approximately 4). At this stage, gammaH2AX-modified chromatin domains are associated with transcriptionally silenced sex chromosomes and autosomal sites. Immunogold electron microscope evidence shows that one or two TNs of the 10-15 TNs per SC acquire MLH1 protein, the hallmark of reciprocal recombination, whereas the TNs that do not acquire MLH1 protein relocate from their positions along the midline of the SCs to the periphery of the SCs. Relocation of TNs may be associated with the conversion of potential crossovers into non-crossovers. PMID- 17344432 TI - MAPK interacts with XGef and is required for CPEB activation during meiosis in Xenopus oocytes. AB - Meiotic progression in Xenopus oocytes, and all other oocytes investigated, is dependent on polyadenylation-induced translation of stockpiled maternal mRNAs. Early during meiotic resumption, phosphorylation of CPE-binding protein (CPEB) is required for polyadenylation-induced translation of mRNAs encoding cell cycle regulators. Xenopus Gef (XGef), a Rho-family guanine-exchange factor, influences the activating phosphorylation of CPEB. An exchange-deficient version of XGef does not, therefore implicating Rho-family GTPase function in early meiosis. We show here that Clostridium difficile Toxin B, a Rho-family GTPase inhibitor, does not impair early CPEB phosphorylation or progression to germinal vesicle breakdown, indicating that XGef does not influence these events through activation of a Toxin-B-sensitive GTPase. Using the inhibitors U0126 for mitogen activated protein kinase (MAPK), and ZM447439 for Aurora kinase A and Aurora kinase B, we found that MAPK is required for phosphorylation of CPEB, whereas Aurora kinases are not. Furthermore, we do not detect active Aurora kinase A in early meiosis. By contrast, we observe an early, transient activation of MAPK, independent of Mos protein expression. MAPK directly phosphorylates CPEB on four residues (T22, T164, S184, S248), but not on S174, a key residue for activating CPEB function. Notably, XGef immunoprecipitates contain MAPK, and this complex can phosphorylate CPEB. MAPK may prime CPEB for phosphorylation on S174 by an as yet-unidentified kinase or may activate this kinase. PMID- 17344433 TI - Lipid rafts in plants. PMID- 17344435 TI - Psychiatric organizations: influencing professional development. PMID- 17344434 TI - Is ozone flux inside leaves only a damage indicator? Clues from volatile isoprenoid studies. PMID- 17344436 TI - The role of professional societies in career development in academic medicine. PMID- 17344437 TI - Why join a subspecialty organization? Membership in the Academy of Psychosomatic Medicine. PMID- 17344439 TI - How the AACDP helped me professionally and personally. PMID- 17344438 TI - The history of the American Association of Chairs of Departments of Psychiatry. PMID- 17344440 TI - Cultivating careers in the American Association of Directors of Psychiatric Residency Training. PMID- 17344441 TI - The American Association for Geriatric Psychiatry: my professional family. PMID- 17344442 TI - Career development in old-age psychiatry: opportunities through the American Association for Geriatric Psychiatry. PMID- 17344443 TI - The Association of Directors of Medical Student Education in Psychiatry. PMID- 17344444 TI - Professional development in forensic psychiatry: the role of the American Academy of Psychiatry and the Law. PMID- 17344445 TI - The unique role of psychiatric organizations and societies in professional development. PMID- 17344446 TI - The Association for Academic Psychiatry. PMID- 17344447 TI - International professional development: the World Psychiatric Association. PMID- 17344448 TI - The American Academy of Child and Adolescent Psychiatry. PMID- 17344449 TI - About the American College of Neuropsychopharmacology. PMID- 17344450 TI - The ACNP and me. PMID- 17344451 TI - Setting a trajectory for career-long professional development. PMID- 17344452 TI - Balancing the personal and the professional: should and can we teach this? PMID- 17344453 TI - The two-physician family: a balancing act of work and love. PMID- 17344454 TI - Life as a balance beam: practical ideas for balancing work and home. PMID- 17344455 TI - Balancing act: a work in progress notes. PMID- 17344456 TI - Child planning required: a father's perspective on balancing career and family within academic psychiatry. PMID- 17344457 TI - Educating, training, and mentoring minority faculty and other trainees in mental health services research. AB - OBJECTIVE: The authors describe the evolution of a novel national training program to develop minority faculty for mental health services research careers. Recruiting, training, and sustaining minority health professionals for academic research careers in mental health services research have proven challenging. METHOD: Over the past 8 years the authors developed NIMH-funded programs to educate, train, and mentor minority psychiatrists and other junior faculty and graduate and post-graduate students. Their areas of academic interest focus primarily on minority mental health issues in primary care and community settings. RESULTS: The authors began with a program that targeted local trainees from the University of New Mexico and expanded to regional and national programs offering weeklong institutes, on-site and distance mentoring by experts, and supportive peer interactions that addressed the considerable challenges affecting trainee career decisions and paths. CONCLUSIONS: Early outcomes support the value of these programs. PMID- 17344458 TI - Training future generations of mental health researchers: devising strategies for tough times. AB - OBJECTIVE: The authors describe a junior faculty scholars program in a large academic department of psychiatry, designed to reduce attrition during the high risk period of transition from post-doctoral fellowship to receipt of the first extramural research award. METHOD: Scholars receive 25% salary support for two years to enable their participation in a research survival skills practicum, mentored collection of pilot data, preparation of manuscripts for peer-reviewed publication, and submission of K23 and K01 proposals. RESULTS: Of 22 junior faculty scholars appointed during the period of 1999-2004, 17 have submitted K award proposals. All were funded on either the first or second submission CONCLUSIONS: A program for junior faculty scholars can provide support for successfully navigating the critical and often difficult transition from post doctoral fellowship to junior faculty. The program is expanding its efforts to assist K awardees in moving successfully along the developmental continuum (e.g., successful submission of R01, development of mentoring skills). PMID- 17344459 TI - UCSD's short-term research training programs for trainees at different levels of career development. AB - OBJECTIVE: There is a critical need for new researchers in psychiatry, including subspecialties such as geriatric psychiatry. Many existing research training programs focus on post-doctoral-level trainees and involve several years of hands on research with experienced mentors at major universities. Although valuable, such programs have some limitations in expanding the pool of investigators in specific areas. In this article, the authors describe several successful short term research training programs. METHOD: The authors, at the University of California, San Diego, coordinate three federally funded programs that take place during the summer and include trainees at different levels from across the United States. These programs are 1) Summer Training on Aging Research Topics-Mental Health (START-MH) for undergraduate, graduate, and medical students; 2) Stein Institute for Research on Aging (SIRA) Medical Student Training In Aging Research (MSTAR); and 3) Summer Research Institute (SRI) in Geriatric Psychiatry for postdoctoral fellows and junior faculty. The authors compare salient characteristics of these programs, illustrating similarities as well as differences. RESULTS: The authors' experience to date suggests that these initiatives have been highly successful in attracting talented trainees at various levels, and the participants have found these experiences useful. The available follow-up suggests positive effects on research career development of the trainees, at least in the shorter run. CONCLUSIONS: There are several possible models that seem to have considerable promise for expanding the pool of scientists in a given field. Limitations of this approach as well as plans for the future are discussed. PMID- 17344460 TI - Teaching interested clinicians how to develop research projects. AB - OBJECTIVE: The authors discuss teaching clinicians about research by generating projects from clinical practice, expertise, and interest. METHOD: Classes were co taught by the hospital biostatistician and clinical nurse specialist in consultation with one of the authors. Hospital clinicians were taught how to initiate and design their study as a follow-up to a Basic Research Skills course previously co-taught by one of the authors. RESULTS: After an early attrition of four, 14 remaining clinicians attended 10 weekly one-hour classes with an average overall attendance rate of 79.5%. Eight of 14 (57%) completed pre- and posttests, with significant improvement in scores from 51% pre-test to 75% posttest. Six research projects were generated from the 14 clinicians. CONCLUSIONS: The authors demonstrated that even busy clinicians can be engaged in the process of developing research projects. An unexpected benefit was the demonstration of mutual respect when sources of expertise taught and learned together. PMID- 17344461 TI - Research during psychiatry residency: a case for IMGs on visas. PMID- 17344463 TI - Environmental and behavioral factors and the risk of non-Hodgkin lymphoma. PMID- 17344464 TI - Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia. AB - A 10-year-old girl with steroid-resistant Diamond-Blackfan anemia (DBA) developed agranulocytosis 9 weeks after chelation with deferiprone was initiated (45 mg/kg daily, 60% of recommended dose) in addition to her ordinary deferoxamine therapy. The blood counts, checked weekly, dropped markedly between weeks 8 and 9. She rapidly developed a septicemia and was admitted with high fever (40.9 degrees C), white blood cell count 0.4 x 10(9)/L, absolute neutrophil count 0.1 x 10(9)/L and platelets 114 x 10(9)/L. She was administered broad spectrum antibiotics, G-CSF (10 microgram/kg daily) and corticosteroids but remained neutropenic and died 6 weeks after admission. Bone marrow examination day 23 revealed areas with low cellularity (around 30%), but also areas with infiltrates of T cells; granulopoiesis and erythropoiesis were scarce. We conclude that weekly neutrophil monitoring is not sufficient to avoid fatal agranulocytosis. We suggest that deferiprone not be prescribed to DBA patients unless the clinical indications are particularly strong, and that the risk of agranulocytosis in thalassemia patients be carefully considered. PMID- 17344465 TI - Direct inhibition of CD40L expression can contribute to the clinical efficacy of daclizumab independently of its effects on cell division and Th1/Th2 cytokine production. AB - Humanized anti-CD25 antibodies (eg, daclizumab) have been successfully used to treat several autoimmune diseases. Paradoxically, IL-2 blockade in mice can induce autoimmunity. An interspecies difference in the relative contribution of IL-2 to CD25(+) T regulatory cell (CD25(+)Treg) versus CD25(+) effector cell function might explain this conundrum. Consistent with this are reports that daclizumab inhibits human CD25(+) effector cell cytokine production by blocking the expression of CD40L. However, in mice, IL-4 and IL-12 regulate CD40L expression. As human Th1/Th2 cytokine production is also dependent on IL-2, daclizumab's inhibition of CD40L expression could be due to an indirect, rather than a direct, effect of IL-2. Here, we clarify the mechanisms underlying CD40L expression. In contrast to the mouse, human CD40L is regulated by CD28 signaling and IL-2, not the principal Th1/Th2-polarizing cytokines. We find that CD40L is expressed on naive and memory cells and inhibited by daclizumab independently of cell division. Collectively, our results indicate that daclizumab could inhibit CD25(+) effector T-cell function in vivo by directly blocking CD40L expression. This difference between mice and human may help explain the paradoxical effects of IL-2R blockade in the 2 species. PMID- 17344466 TI - Nelarabine induces complete remissions in adults with relapsed or refractory T lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. AB - Nelarabine (506U78) is a soluble pro-drug of 9-beta-D-arabinofuranosylguanine (ara-G), a deoxyguanosine derivative. We treated 26 patients with T-cell acute lymphoblastic leukemia (T-ALL) and 13 with T-cell lymphoblastic lymphoma (T-LBL) with nelarabine. All patients were refractory to at least one multiagent regimen or had relapsed after achieving a complete remission. Nelarabine was administered on an alternate day schedule (days 1, 3, and 5) at 1.5 g/m(2)/day. Cycles were repeated every 22 days. The median age was 34 years (range, 16-66 years); 32 (82%) patients were male. The rate of complete remission was 31% (95% confidence interval [CI], 17%, 48%) and the overall response rate was 41% (95% CI, 26%, 58%). The principal toxicity was grade 3 or 4 neutropenia and thrombocytopenia, occurring in 37% and 26% of patients, respectively. There was only one grade 4 adverse event of the nervous system, which was a reversible depressed level of consciousness. The median disease-free survival (DFS) was 20 weeks (95% CI, 11, 56), and the median overall survival was 20 weeks (95% CI, 13, 36). The 1-year overall survival was 28% (95% CI, 15%, 43%). Nelarabine is well tolerated and has significant antitumor activity in relapsed or refractory T-ALL and T-LBL. PMID- 17344467 TI - A CD99-related antigen on endothelial cells mediates neutrophil but not lymphocyte extravasation in vivo. AB - CD99 is a long-known leukocyte antigen that does not belong to any of the known protein families. It was recently found on endothelial cells, where it mediates transendothelial migration of human monocytes and lymphocyte recruitment into inflamed skin in the mouse. Here, we show that CD99L2, a recently cloned, widely expressed antigen of unknown function with moderate sequence homology to CD99, is expressed on mouse leukocytes and endothelial cells. Using antibodies, we found that CD99L2 and CD99 are involved in transendothelial migration of neutrophils in vitro and in the recruitment of neutrophils into inflamed peritoneum. Intravital and electron microscopy of cremaster venules revealed that blocking CD99L2 inhibited leukocyte transmigration through the vessel wall (diapedesis) at the level of the perivascular basement membrane. We were surprised to find that, in contrast to CD99, CD99L2 was not relevant for the extravasation of lymphocytes into inflamed tissue. Although each protein promoted cell aggregation of transfected cells, endothelial CD99 and CD99L2 participated in neutrophil extravasation independent of these proteins on neutrophils. Our results establish CD99L2 as a new endothelial surface protein involved in neutrophil extravasation. In addition, this is the first evidence for a role of CD99 and CD99L2 in the process of leukocyte diapedesis in vivo. PMID- 17344468 TI - Catsper3 and Catsper4 are essential for sperm hyperactivated motility and male fertility in the mouse. AB - Catsper3 and Catsper4 are two recently identified testis-specific genes homologous to Catsper1 and Catsper2 that have been shown to play an essential role in sperm hyperactivated motility and male fertility in mice. Here we report that Catsper3 and Catsper4 knockout male mice are completely infertile due to a quick loss of motility and a lack of hyperactivated motility under capacitating conditions. Our data demonstrate that both CATSPER3 and CATSPER4 are required for hyperactivated sperm motility during capacitation and for male fertility. The present study also demands a revisit to the idiopathic male infertility patients who show normal sperm counts and normal initial motility for defects in sperm hyperactivated motility and for potential CATSPER gene mutations. The CATSPER channel also may be an excellent drug target for male contraceptives. PMID- 17344469 TI - Novel aspects of the sperm-associated antigen 11 (SPAG11) gene organization and expression in cattle (Bos taurus). AB - Beta-defensins are small cationic peptides exhibiting broad spectrum antimicrobial properties. In humans, many beta-defensin genes are located within a cluster on chromosome 8p23. The sperm associated antigen 11 (SPAG11) gene is contained in this cluster and is unusual among the human beta-defensins due to its complex genomic structure and mRNA splicing pattern. Here we report the genomic organization of the Bos taurus SPAG11 gene located on chromosome 27q1.2, within a cluster of beta-defensin genes. The exon structures of the fused bovine SPAG11 gene and of the mosaic transcripts initiated at both A and B promoters were established, including identification of novel exons and transcripts not previously found in primate or rodent. Evolutionary analysis against primate, rodent, canine, and porcine orthologs was performed. In adult bulls SPAG11C, SPAG11E, and SPAG11U mRNAs were detected predominantly in the male reproductive tract, while SPAG11D transcript was detected in reproductive and nonreproductive tissues and SPAG11V and SPAG11W mRNAs were confined to testis. Differential expression of all six transcripts was observed in tissues from fetal and adult bulls, suggesting that similar mRNA splicing mechanisms govern SPAG11 gene expression during pre- and postnatal development. Immunolocalization of SPAG11C and SPAG11D/E was demonstrated in the epithelium of the epididymis and testis, and SPAG11D in association with epididymal spermatozoa. Recombinant full-length SPAG11D protein was strongly antibacterial, while the SPAG11E C-terminal peptide that contains the beta-defensin motif in its structure was somewhat less potent. Taken together, the results suggest that SPAG11 isoforms perform both immune and reproductive functions in cattle. PMID- 17344470 TI - Impact of dietary fatty acids on oocyte quality and development in lactating dairy cows. AB - The purpose of this study was to examine the effects of level of rumen inert fatty acids on developmental competence of oocytes in lactating dairy cows. Estrous cycles were synchronized in 22 cows on a silage-based diet supplemented with either low (200 g/day) or high (800 g/day) fat. A total of 1051 oocytes were collected by ultrasound-guided ovum pickup (OPU) in seven sessions/cow at 3-4 day intervals. Oocytes were matured, fertilized, and cultured to the blastocyst stage in vitro. Embryo quality was assessed by differential staining of Day 8 blastocysts. The high-fat diet reduced numbers of small and medium follicles. There was no effect on the quality of oocytes (grades 1-4) or cleavage rate. However, high fat significantly improved blastocyst production from matured (P < 0.005) and cleaved (P < 0.05) oocytes. Blastocysts from the high-fat group had significantly more total, inner cell mass and trophectoderm cells than the low fat group (P < 0.05). Regression analysis showed negative effects of milk yield (P < 0.001), dry matter intake (P < 0.001), metabolizable energy intake (P < 0.005), and starch intake (P < 0.001) on blastocyst production in the low-fat group but not in the high-fat group. Within the low-fat group, blastocyst production was negatively related to growth hormone (P < 0.05) and positively related to leptin (P < 0.05). The low-fat group had higher nonesterified fatty acids than the high-fat group (P < 0.05). In conclusion, higher milk yields were associated with reduced developmental potential of oocytes in cows given a low fat diet. Provision of a high-fat diet buffered oocytes against these effects, resulting in significantly improved developmental potential. PMID- 17344471 TI - Anterior pituitary gene expression with reproductive aging in the female rat. AB - Although reproductive aging in women is classically attributed to loss of ovarian follicles, recent data have suggested that the entire hypothalamic-pituitary ovarian axis undergoes functional changes with time. The aim of this study was to characterize age-related changes in pituitary gene expression for factors with known importance for gonadotroph function, including 1) steroid hormone receptors (Esr and Pgr), 2) orphan nuclear receptors [Nr5a1 (steroidogenic factor-1) and Nr5a2 (liver receptor homologue-1)], and 3) pituitary-derived polypeptides (activin, inhibin, and follistatin), as well as 4) gonadotropin subunits and 5) GnRH receptors. We chose to utilize a middle-aged rat model for these studies. Young (Y; 3-mo-old) and middle-aged (MA; 9- to 12-mo-old) rats were ovariectomized, primed with estradiol, and injected with progesterone to induce an LH surge. The mRNA levels for the gonadotropin subunits and GnRH receptors were decreased in middle-aged females relative to young animals. Nr5a1 and follistatin mRNA levels were significantly greater in Y versus MA animals following ovariectomy. Furthermore, steroid-induced regulation of these genes was lost in the MA animals. Regulation of the Nr5a2, Inhba, and Inhbb transcripts was also limited to the young animals. In contrast, there were no significant differences in the mRNA levels of Esr or Pgr family members between age groups at any time point. Although this in vivo model normalizes ovarian steroid levels, it does not control for potential differences in GnRH stimulation with aging. Therefore, in a second set of experiments, we used an in vitro perifusion system to compare the effects of pulsatile GnRH in the two age groups. Nr5a1 mRNA expression was greater in Y than MA animals and was significantly decreased by GnRH pulses in both age groups. Follistatin mRNA levels increased significantly with GnRH treatment in Y animals but were not significantly changed in the MA females. Taken together, these data demonstrate gene-specific blunting of pituitary gene expression postovariectomy and during the steroid-induced surge in middle-aged rats. We propose that age-related changes in pituitary physiology may contribute to reproductive senescence. PMID- 17344472 TI - Interphase-specific phosphorylation-mediated regulation of tubulin dimer partitioning in human cells. AB - The microtubule cytoskeleton is differentially regulated by a diverse array of proteins during interphase and mitosis. Op18/stathmin (Op18) and microtubule associated protein (MAP)4 have been ascribed opposite general microtubule directed activities, namely, microtubule destabilization and stabilization, respectively, both of which can be inhibited by phosphorylation. Here, using three human cell models, we depleted cells of Op18 and/or MAP4 by expression of interfering hairpin RNAs and we analyzed the resulting phenotypes. We found that the endogenous levels of Op18 and MAP4 have opposite and counteractive activities that largely govern the partitioning of tubulin dimers in the microtubule array at interphase. Op18 and MAP4 were also found to be the downstream targets of Ca(2+)- and calmodulin-dependent protein kinase IV and PAR-1/MARK2 kinase, respectively, that control the demonstrated counteractive phosphorylation mediated regulation of tubulin dimer partitioning. Furthermore, to address mechanisms regulating microtubule polymerization in response to cell signals, we developed a system for inducible gene product replacement. This approach revealed that site-specific phosphorylation of Op18 is both necessary and sufficient for polymerization of microtubules in response to the multifaceted signaling event of stimulation of the T cell antigen receptor complex, which activates several signal transduction pathways. PMID- 17344474 TI - Conformational dynamics of the major yeast phosphatidylinositol transfer protein sec14p: insight into the mechanisms of phospholipid exchange and diseases of sec14p-like protein deficiencies. AB - Molecular dynamics simulations coupled with functional analyses of the major yeast phosphatidylinositol/phosphatidylcholine transfer protein Sec14p identify structural elements involved in regulating the ability of Sec14p to execute phospholipid exchange. The molecular dynamics simulations suggest large rigid body motions within the Sec14p molecule accompany closing and opening of an A(10)/T(4)/A(11) helical gate, and that "state-of-closure" of this helical gate determines access to the Sec14p phospholipid binding cavity. The data also project that conformational dynamics of the helical gate are controlled by a hinge unit (residues F(212), Y(213), K(239), I(240), and I(242)) that links to the N- and C-terminal ends of the helical gate, and by a novel gating module (composed of the B(1)LB(2) and A(12)LT(5) substructures) through which conformational information is transduced to the hinge. The (114)TDKDGR(119) motif of B(1)LB(2) plays an important role in that transduction process. These simulations offer new mechanistic possibilities for an important half-reaction of the Sec14p phospholipid exchange cycle that occurs on membrane surfaces after Sec14p has ejected bound ligand, and is reloading with another phospholipid molecule. These conformational transitions further suggest structural rationales for known disease missense mutations that functionally compromise mammalian members of the Sec14-protein superfamily. PMID- 17344473 TI - Specialized roles of the two mitotic cyclins in somatic cells: cyclin A as an activator of M phase-promoting factor. AB - The role of cyclin B-CDC2 as M phase-promoting factor (MPF) is well established, but the precise functions of cyclin A remain a crucial outstanding issue. Here we show that down-regulation of cyclin A induces a G2 phase arrest through a checkpoint-independent inactivation of cyclin B-CDC2 by inhibitory phosphorylation. The phenotype is rescued by expressing cyclin A resistant to the RNA interference. In contrast, down-regulation of cyclin B disrupts mitosis without inactivating cyclin A-CDK, indicating that cyclin A-CDK acts upstream of cyclin B-CDC2. Even when ectopically expressed, cyclin A cannot replace cyclin B in driving mitosis, indicating the specific role of cyclin B as a component of MPF. Deregulation of WEE1, but not the PLK1-CDC25 axis, can override the arrest caused by cyclin A knockdown, suggesting that cyclin A-CDK may tip the balance of the cyclin B-CDC2 bistable system by initiating the inactivation of WEE1. These observations show that cyclin A cannot form MPF independent of cyclin B and underscore a critical role of cyclin A as a trigger for MPF activation. PMID- 17344475 TI - Ent3p and Ent5p exhibit cargo-specific functions in trafficking proteins between the trans-Golgi network and the endosomes in yeast. AB - The phosphoinositide-binding proteins Ent3p and Ent5p are required for protein transport from the trans-Golgi network (TGN) to the vacuole in Saccharomyces cerevisiae. Both proteins interact with the monomeric clathrin adaptor Gga2p, but Ent5p also interacts with the clathrin adaptor protein 1 (AP-1) complex, which facilitates retention of proteins such as Chs3p at the TGN. When both ENT3 and ENT5 are mutated, Chs3p is diverted from an intracellular reservoir to the cell surface. However, Ent3p and Ent5p are not required for the function of AP-1, but rather they seem to act in parallel with AP-1 to retain proteins such as Chs3p at the TGN. They have all the properties of clathrin adaptors, because they can both bind to clathrin and to cargo proteins. Like AP-1, Ent5p binds to Chs3p, whereas Ent3p facilitates the interaction between Gga2p and the endosomal syntaxin Pep12p. Thus, Ent3p has an additional function in Gga-dependent transport to the late endosome. Ent3p also facilitates the association between Gga2p and clathrin; however, Ent5p can partially substitute for this function. We conclude that the clathrin adaptors AP-1, Ent3p, Ent5p, and the Ggas cooperate in different ways to sort proteins between the TGN and the endosomes. PMID- 17344476 TI - The transcriptional repressor Glis2 is a novel binding partner for p120 catenin. AB - In epithelial cells, p120 catenin (p120) localizes at cell-cell contacts and regulates adhesive function of the cadherin complex. In addition, p120 has been reported to localize in the nucleus, although the nuclear function of p120 is not fully understood. Here, we report the identification of Gli-similar 2 (Glis2) as a novel binding protein for p120. Glis2 is a Kruppel-like transcriptional repressor with homology to the Gli family, but its physiological function has not been well characterized. In this study, we show that coexpression of Glis2 and Src induces nuclear translocation of p120. Furthermore, p120 induces the C terminal cleavage of Glis2, and this cleavage is further enhanced by Src. The cleaved form of Glis2 loses one of its five zinc finger domains, but it is still able to bind DNA. Functional studies in chick neural tube indicate that full length Glis2 can affect neuronal differentiation, whereas the cleaved form requires coexpression of p120 to have a similar effect. These data indicate that p120 has additional novel functions in the nucleus together with Glis2. PMID- 17344477 TI - Oxa1 directly interacts with Atp9 and mediates its assembly into the mitochondrial F1Fo-ATP synthase complex. AB - The yeast Oxa1 protein is involved in the biogenesis of the mitochondrial oxidative phosphorylation (OXPHOS) machinery. The involvement of Oxa1 in the assembly of the cytochrome oxidase (COX) complex, where it facilitates the cotranslational membrane insertion of mitochondrially encoded COX subunits, is well documented. In this study we have addressed the role of Oxa1, and its sequence-related protein Cox18/Oxa2, in the biogenesis of the F(1)F(o)-ATP synthase complex. We demonstrate that Oxa1, but not Cox18/Oxa2, directly supports the assembly of the membrane embedded F(o)-sector of the ATP synthase. Oxa1 was found to physically interact with newly synthesized mitochondrially encoded Atp9 protein in a posttranslational manner and in a manner that is not dependent on the C-terminal, matrix-localized region of Oxa1. The stable manner of the Atp9 Oxa1 interaction is in contrast to the cotranslational and transient interaction previously observed for the mitochondrially encoded COX subunits with Oxa1. In the absence of Oxa1, Atp9 was observed to assemble into an oligomeric complex containing F(1)-subunits, but its further assembly with subunit 6 (Atp6) of the F(o)-sector was perturbed. We propose that by directly interacting with newly synthesized Atp9 in a posttranslational manner, Oxa1 is required to maintain the assembly competence of the Atp9-F(1)-subcomplex for its association with Atp6. PMID- 17344478 TI - GGA2- and ubiquitin-dependent trafficking of Arn1, the ferrichrome transporter of Saccharomyces cerevisiae. AB - The intracellular trafficking of Arn1, a ferrichrome transporter in Saccharomyces cerevisiae, is controlled in part by the binding of ferrichrome to the transporter. In the absence of ferrichrome, Arn1 is sorted directly from the Golgi to endosomes. Ferrichrome binding triggers the redistribution of Arn1 to the plasma membrane, whereas ferrichrome transport is associated with the cycling of Arn1 between the plasma membrane and endosomes. Here, we report that the clathrin adaptor Gga2 and ubiquitination by the Rsp5 ubiquitin ligase are required for trafficking of Arn1. Gga2 was required for Golgi-to-endosomal trafficking of Arn1, which was sorted from endosomes to the vacuole for degradation. Trafficking into the vacuolar lumen was dependent on ubiquitination by Rsp5, but ubiquitination was not required for plasma membrane accumulation of Arn1 in the presence of ferrichrome. Retrograde trafficking via the retromer complex or Snx4 was also not required for plasma membrane accumulation. High concentrations of ferrichrome led to higher levels of ubiquitination of Arn1, but they did not induce degradation. Without this ubiquitination, Arn1 remained on the plasma membrane, where it was active for transport. Arn1 was preferentially modified with polyubiquitin chains on a cluster of lysine residues at the amino terminus of the transporter. PMID- 17344479 TI - Slug is required for cell survival during partial epithelial-mesenchymal transition of HGF-induced tubulogenesis. AB - Transcription factors of the Snail family are key regulators of epithelial mesenchymal transition (EMT). In many processes during development or disease, cells do not acquire all the characteristics associated with EMT, leading to what we refer to as partial EMT (p-EMT). However, little is known of the implications of the Snail transcription factors in processes that only involve a p-EMT. To assess this, we used the hepatocyte growth factor (HGF)-induced Madin-Darby canine kidney tubulogenesis system, which provides a three-dimensional culture model of a morphogenetic process including a p-EMT. We found that although Slug (Snail2) is highly and transitory up-regulated during the p-EMT phase of tubulogenesis, it is not a repressor of E-cadherin during this process. Using inducible knockdown of Slug, we demonstrate that Slug is not an inducer of cell movement and instead is required for survival during p-EMT. We conclude that in epithelial cells, promoting cell survival can be a primary function of Slug, rather than being acquired concomitantly with EMT. PMID- 17344480 TI - Yeast formins Bni1 and Bnr1 utilize different modes of cortical interaction during the assembly of actin cables. AB - The budding yeast formins Bni1 and Bnr1 control the assembly of actin cables. These formins exhibit distinct patterns of localization and polymerize two different populations of cables: Bni1 in the bud and Bnr1 in the mother cell. We generated a functional Bni1-3GFP that improved the visualization of Bni1 in vivo at endogenous levels. Bni1 exists as speckles in the cytoplasm, some of which colocalize on actin cables. These Bni1 speckles display linear, retrograde directed movements. Loss of polymerized actin or specifically actin cables abolished retrograde movement, and resulted in depletion of Bni1 speckles from the cytoplasm, with enhanced targeting of Bni1 to the bud tip. Mutations that impair the actin assembly activity of Bni1 abolished the movement of Bni1 speckles, even when actin cables were present. In contrast, Bnr1-GFP or 3GFP-Bnr1 did not detectably associate with actin cables and was not observed as cytoplasmic speckles. Finally, fluorescence recovery after photobleaching demonstrated that Bni1 was very dynamic, exchanging between polarized sites and the cytoplasm, whereas Bnr1 was confined to the bud neck and did not exchange with a cytoplasmic pool. In summary, our results indicate that formins can have distinct modes of cortical interaction during actin cable assembly. PMID- 17344482 TI - A Ser/Thr kinase required for membrane-associated assembly of the major sperm protein motility apparatus in the amoeboid sperm of Ascaris. AB - Leading edge protrusion in the amoeboid sperm of Ascaris suum is driven by the localized assembly of the major sperm protein (MSP) cytoskeleton in the same way that actin assembly powers protrusion in other types of crawling cell. Reconstitution of this process in vitro led to the identification of two accessory proteins required for MSP polymerization: an integral membrane phosphoprotein, MSP polymerization-organizing protein (MPOP), and a cytosolic component, MSP fiber protein 2 (MFP2). Here, we identify and characterize a 34 kDa cytosolic protein, MSP polymerization-activating kinase (MPAK) that links the activities of MPOP and MFP2. Depletion/add-back assays of sperm extracts showed that MPAK, which is a member of the casein kinase 1 family of Ser/Thr protein kinases, is required for motility. MPOP and MPAK comigrated by native gel electrophoresis, coimmunoprecipitated, and colocalized by immunofluorescence, indicating that MPOP binds to and recruits MPAK to the membrane surface. MPAK, in turn, phosphorylated MFP2 on threonine residues, resulting in incorporation of MFP2 into the cytoskeleton. Beads coated with MPAK assembled a surrounding cloud of MSP filaments when incubated in MPAK-depleted sperm extract, but only when supplemented with detergent-solubilized MPOP. Our results suggest that interactions involving MPOP, MPAK, and MFP2 focus MSP polymerization to the plasma membrane at the leading edge of the cell thereby generating protrusion and minimizing nonproductive filament formation elsewhere. PMID- 17344481 TI - R-Ras regulates exocytosis by Rgl2/Rlf-mediated activation of RalA on endosomes. AB - R-Ras is a Ras-family small GTPase that regulates various cellular functions such as apoptosis and cell adhesion. Here, we demonstrate a role of R-Ras in exocytosis. By the use of specific anti-R-Ras antibody, we found that R-Ras was enriched on both early and recycling endosomes in a wide range of cell lines. Using a fluorescence resonance energy transfer-based probe for R-Ras activity, R Ras activity was found to be higher on endosomes than on the plasma membrane. This high R-Ras activity on the endosomes correlated with the accumulation of an R-Ras effector, the Rgl2/Rlf guanine nucleotide exchange factor for RalA, and also with high RalA activity. The essential role played by R-Ras in inducing high levels of RalA activity on the endosomes was evidenced by the short hairpin RNA (shRNA)-mediated suppression of R-Ras and by the expression of R-Ras GAP. In agreement with the reported role of RalA in exocytosis, the shRNA of either R-Ras or RalA was found to suppress calcium-triggered exocytosis in PC12 pheochromocytoma cells. These data revealed that R-Ras activates RalA on endosomes and that it thereby positively regulates exocytosis. PMID- 17344483 TI - Do n-3 fatty acids prevent osteoporosis? PMID- 17344484 TI - The urgent need to recommend an intake of vitamin D that is effective. PMID- 17344485 TI - Liquid calories, sugar, and body weight. AB - The consumption of sugar-sweetened beverages has been linked to rising rates of obesity in the United States. The standard explanation is that energy-containing liquids are less satiating than are solid foods. However, purely physiologic mechanisms do not fully account for the proposed links between liquid sugar energy and body weight change. First, a reevaluation of published epidemiologic studies of consumption of sweetened beverages and overweight shows that most such studies either are cross-sectional or are based on passive surveillance of temporal trends and thus permit no conclusions about causal links. Second, research evidence comparing the short-term satiating power of different types of liquids and of solids remains inconclusive. Numerous clinical studies have shown that sugar-containing liquids, when consumed in place of usual meals, can lead to a significant and sustained weight loss. The principal ingredient of liquid meal replacement shakes is sugar, often high-fructose corn syrup, which is present in amounts comparable to those in soft drinks. Far from suppressing satiety, one such liquid shake is marketed on the grounds that it helps control hunger and prevents hunger longer when consumed for the purpose of weight loss. These inconsistencies raise the question whether the issue of sugars and body weight should continue to be framed purely in metabolic or physiologic terms. The effect of sugar consumption on body weight can also depend on behavioral intent, context, and the mode of use, availability, and cost of sweetened liquids. PMID- 17344486 TI - Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise. AB - Mounting evidence indicates that elevated intramyocellular triacylglycerol concentrations are associated with diminished insulin sensitivity in skeletal muscle. This lipid accumulation is most likely due to enhanced fatty acid uptake into the muscle coupled with diminished mitochondrial lipid oxidation. The excess fatty acids are esterified and either stored or metabolized to various molecules that may participate or interfere with normal cellular signaling, particularly insulin-mediated signal transduction, thus altering cellular and, subsequently, whole-body glucose metabolism. Impaired insulin responsiveness, if not managed, can further progress to type 2 diabetes mellitus, an all too common condition. For most of the human population this is avoidable, given that causes of intramyocellular lipid deposition are predominantly lifestyle-mediated. Chronic overconsumption of calories coupled with deleterious intakes of saturated or trans-unsaturated fatty acids inconsistent with the recommendations outlined in the Dietary Guidelines for Americans have been shown to increase the risk of insulin resistance. Furthermore, lack of exercise, which can have a profound effect on skeletal muscle lipid turnover, is implicated in this lipid-induced insulin resistance. This review summarizes the current understanding of the effects of elevated intramyocellular lipids on insulin signaling and how these effects may be altered by varying dietary fat composition and exercise. PMID- 17344487 TI - Effect of dairy calcium or supplementary calcium intake on postprandial fat metabolism, appetite, and subsequent energy intake. AB - BACKGROUND: High calcium intake has been shown to increase fecal fat excretion. OBJECTIVE: Our aim was to examine whether a high calcium intake from dairy products or from supplements affects postprandial fat metabolism and appetite through fat malabsorption. DESIGN: Four different isocaloric meals were tested in 18 subjects according to a randomized crossover design. The test meals contained high (HC meal: 172 mg/MJ), medium (MC meal: 84 mg/MJ), or low (LC meal: 15 mg/MJ) amounts of calcium from dairy products or a high amount of calcium given as a calcium carbonate supplement (Suppl meal: 183 mg/MJ). Concentrations of plasma total triacylglycerol, chylomicron triacylglycerol, serum total cholesterol, HDL cholesterol, cholecystokinin, glucagon-like peptide 1, ghrelin, peptide YY, glucose, and insulin and appetite sensation were measured before and at regular intervals until 420 min postprandially. RESULTS: Dairy calcium significantly diminished the postprandial lipid response. The baseline adjusted area under the curve for chylomicron triacylglycerol was approximately 17% lower after the MC meal (P = 0.02) and approximately 19% lower after the HC meal (P = 0.007) than after the LC meal and approximately 15% lower after the MC meal (P = 0.0495) and approximately 17% lower after the HC meal (P = 0.02) than after the Suppl meal. No consistent effects of calcium on appetite sensation, or on energy intake at the subsequent meal, or on the postprandial responses of cholecystokinin, glucagon-like peptide 1, ghrelin, peptide YY, insulin, or glucose were observed. CONCLUSIONS: Increased calcium intakes from dairy products attenuate postprandial lipidemia, most probably because of reduced fat absorption, whereas supplementary calcium carbonate does not exert such an effect. This may be due to differences in the chemical form of calcium or to cofactors in dairy products. Calcium did not affect appetite sensation, glucose metabolism, or gut hormone secretion. PMID- 17344488 TI - Relation of nutrients and hormones in polycystic ovary syndrome. AB - BACKGROUND: Insulin resistance, infertility, and hirsutism, common characteristics of polycystic ovary syndrome (PCOS), improve with even modest weight loss. Optimal dietary treatment for PCOS is not known. OBJECTIVE: We compared the effects of acute protein administration with those of glucose challenges on hormones related to obesity and insulin resistance (ie, cortisol and insulin), hirsutism [ie, dehydroepiandosterone (DHEA) and androstenedione], and hunger (ie, ghrelin). DESIGN: Patients with PCOS (n = 28; aged 26 +/- 2 y) were tested with a 5-h oral-glucose-tolerance test (OGTT) and a euvolemic, euenergetic protein challenge. RESULTS: Glucose ingestion caused larger fluctuations in blood glucose and more hyperinsulinemia than did protein (P < 0.01, overall treatment-by-time interaction). During the protein challenge, cortisol and DHEA declined over 5 h. During OGTT, cortisol and DHEA increased after the third hour and began to show significant divergence from protein from the fourth hour (P 10 mg/L (2.39; 1.34, 4.11). Finally, appetite loss was associated with worse clinical outcome even after adjustment for age, sex, inflammation, dialysis vintage, and comorbidity (likelihood ratio = 44.3; P < 0.0001). CONCLUSIONS: These results show a close association among appetite, malnutrition, inflammation, and outcome in patients undergoing prevalent hemodialysis. Moreover, our data suggest that uremic men may be more susceptible than are women to inflammation-induced anorexia. PMID- 17344490 TI - Choline-related supplements improve abnormal plasma methionine-homocysteine metabolites and glutathione status in children with cystic fibrosis. AB - BACKGROUND: Liver triacylglycerol accumulation and oxidative stress are common in cystic fibrosis (CF) and also occur in choline deficiency. Previously, we showed an association between elevated plasma homocysteine, reduced ratios of S adenosylmethionine to S-adenosylhomocysteine (SAM:SAH) and of phosphatidylcholine to phosphatidylethanolamine, and phospholipid malabsorption in children with CF. OBJECTIVE: The objective was to address a possible relation between altered methionine-homocysteine metabolism and choline metabolism in children with CF. DESIGN: Children with CF were assigned without bias to supplementation with 2 g lecithin/d (n = 13), 2 g choline/d (n = 12), or 3 g betaine/d (n = 10) for 14 d. Plasma concentrations of methionine, adenosine, cysteine, cysteinyl-glycine, glutathione, glutathione disulfide (GSSG), and fatty acids; SAM:SAH; and red blood cell phospholipids were measured within each group of children with CF before and after supplementation. Plasma from healthy children without CF (n = 15) was analyzed to obtain reference data. RESULTS: Children with CF had higher plasma homocysteine, SAH, and adenosine and lower methionine, SAM:SAH, and glutathione:GSSG than did children without CF. Supplementation with lecithin, choline, or betaine resulted in a significant increase in plasma methionine, SAM, SAM:SAH, and glutathione:GSSG and a decrease in SAH (n = 35). Supplementation with choline or betaine was associated with a significant decrease in plasma SAH and an increase in SAM:SAH, methionine, and glutathione:GSSG. Supplementation with lecithin or choline also increased plasma methionine and SAM. CONCLUSION: We showed that dietary supplementation with choline-related compounds improves the low SAM:SAH and glutathione redox balance in children with CF. PMID- 17344491 TI - Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. AB - BACKGROUND: Cocoa powder is rich in polyphenols such as catechins and procyanidins and has been shown in various models to inhibit LDL oxidation and atherogenesis. OBJECTIVE: We examined whether long-term intake of cocoa powder alters plasma lipid profiles in normocholesterolemic and mildly hypercholesterolemic human subjects. DESIGN: Twenty-five subjects were randomly assigned to ingest either 12 g sugar/d (control group) or 26 g cocoa powder and 12 g sugar/d (cocoa group) for 12 wk. Blood samples were collected before the study and 12 wk after intake of the test drinks. Plasma lipids, LDL oxidative susceptibility, and urinary oxidative stress markers were measured. RESULTS: At 12 wk, we measured a 9% prolongation from baseline levels in the lag time of LDL oxidation in the cocoa group. This prolongation in the cocoa group was significantly greater than the reduction measured in the control group (-13%). A significantly greater increase in plasma HDL cholesterol (24%) was observed in the cocoa group than in the control group (5%). A negative correlation was observed between plasma concentrations of HDL cholesterol and oxidized LDL. At 12 wk, there was a 24% reduction in dityrosine from baseline concentrations in the cocoa group. This reduction in the cocoa group was significantly greater than the reduction in the control group (-1%). CONCLUSION: It is possible that increases in HDL-cholesterol concentrations may contribute to the suppression of LDL oxidation and that polyphenolic substances derived from cocoa powder may contribute to an elevation in HDL cholesterol. PMID- 17344492 TI - Coffee intake and incidence of hypertension. AB - BACKGROUND: The long-term longitudinal evidence for a relation between coffee intake and hypertension is relatively scarce. OBJECTIVE: The objective was to assess whether coffee intake is associated with the incidence of hypertension. DESIGN: This study was conducted on a cohort of 2985 men and 3383 women who had a baseline visit and follow-up visits after 6 and 11 y. Baseline coffee intake was ascertained with questionnaires and categorized into 0, >0-3, >3-6, and >6 cups/d. Hypertension was defined as a mean systolic blood pressure (SBP) >or=140 mm Hg over both follow-up measurements, a mean diastolic blood pressure (DBP) >or=90 mm Hg over both follow-up measurements, or the use of antihypertensive medication at any follow-up measurement. RESULTS: Coffee abstainers at baseline had a lower risk of hypertension than did those with a coffee intake of >0-3 cups/d [odds ratio (OR): 0.54; 95% CI: 0.31, 0.92]. Women who drank >6 cups/d had a lower risk than did women who drank >0-3 cups/d (OR: 0.67; 95% CI: 0.46, 0.98). Subjects aged >or=39 y at baseline had 0.35 mm Hg (95% CI: -0.59, -0.11 mm Hg) lower SBP per cup intake/d and 0.11 mm Hg lower DBP (95% CI: -0.26, 0.03 mm Hg) than did those aged <39 y at baseline, although the difference in DBP was not statistically significant. CONCLUSIONS: Coffee abstinence is associated with a lower hypertension risk than is low coffee consumption. An inverse U-shaped relation between coffee intake and risk of hypertension was observed in the women. PMID- 17344493 TI - Effects of a reduced-glycemic-load diet on body weight, body composition, and cardiovascular disease risk markers in overweight and obese adults. AB - BACKGROUND: Lowering the dietary glycemic load and increasing protein intake may be advantageous for weight management. OBJECTIVE: This randomized controlled trial was designed to evaluate the effects of an ad libitum reduced-glycemic-load (RGL) diet on body weight, body composition, and cardiovascular disease (CVD) risk markers in overweight and obese adults during an initial weight-loss phase (12 wk) and a weight-loss maintenance phase (weeks 24-36). DESIGN: Subjects were assigned to RGL (n = 43) or low-fat, portion-controlled (control; n = 43) diet groups. The RGL group was instructed to eat until satisfied, maintaining a low carbohydrate intake during weeks 0-2 and adding low-glycemic-index carbohydrate thereafter. Control subjects were instructed to reduce fat intake and decrease portion sizes, with a targeted energy deficit of 500 to 800 kcal/d. RESULTS: The RGL group had lost significantly more weight than did the control group at week 12 (-4.9 and -2.5 kg, respectively; P = 0.002), but the 2 groups did not differ significantly at week 36 (-4.5 and -2.6 kg, respectively; P = 0.085). Changes in fat mass differed between the groups at week 12 (-1.9 and -0.9 kg, respectively; P = 0.016) but not at week 36 (-2.0 and -1.3 kg, respectively; P = 0.333). At the end of the study, no differences were found in responses for CVD risk markers except a larger mean change in HDL cholesterol in the RGL group than in the control group (3.8 and 1.9 mg/dL, respectively; P = 0.037). CONCLUSION: These findings provide evidence that an ad libitum RGL diet is a reasonable alternative to a low-fat, portion-controlled eating plan for weight management. PMID- 17344494 TI - Soy inclusion in the diet improves features of the metabolic syndrome: a randomized crossover study in postmenopausal women. AB - BACKGROUND: Little evidence exists regarding the effects of soy consumption on the metabolic syndrome in humans. OBJECTIVE: We aimed to determine the effects of soy consumption on components of the metabolic syndrome, plasma lipids, lipoproteins, insulin resistance, and glycemic control in postmenopausal women with the metabolic syndrome. DESIGN: This randomized crossover clinical trial was undertaken in 42 postmenopausal women with the metabolic syndrome. Participants were randomly assigned to consume a control diet (Dietary Approaches to Stop Hypertension, DASH), a soy-protein diet, or a soy-nut diet, each for 8 wk. Red meat in the DASH period was replaced by soy-protein in the soy-protein period and by soy-nut in the soy-nut period. RESULTS: The soy-nut regimen decreased the homeostasis model of assessment-insulin resistance score significantly compared with the soy-protein (difference in percentage change: -7.4 +/- 0.8; P < 0.01) or control (-12.9 +/- 0.9; P < 0.01) diets. Consumption of soy-nut also reduced fasting plasma glucose more significantly than did the soy-protein (-5.3 +/- 0.5%; P < 0.01) or control (-5.1 +/- 0.6%; P < 0.01) diet. The soy-nut regimen decreased LDL cholesterol more than did the soy-protein period (-5.0 +/- 0.6%; P < 0.01) and the control (-9.5 +/- 0.6%; P < 0.01) diet. Soy-nut consumption significantly reduced serum C-peptide concentrations compared with control diet ( 8.0 +/- 2.1; P < 0.01), but consumption of soy-protein did not. CONCLUSION: Short term soy-nut consumption improved glycemic control and lipid profiles in postmenopausal women with the metabolic syndrome. PMID- 17344495 TI - Evaluation of a portable device to measure daily energy expenditure in free living adults. AB - BACKGROUND: Increasing daily energy expenditure (EE) plays an important role in the prevention or treatment of several lifestyle-related diseases; however, its measurement remains problematic. OBJECTIVE: The objective was to evaluate a portable armband device for measuring daily and physical activity EE compared with doubly labeled water (DLW) in free-living individuals. DESIGN: Daily EE and physical activity EE were measured in 45 subjects over a 10-d period simultaneously with 2 techniques: a portable armband and DLW. Resting metabolic rate was measured by indirect calorimetry, and the thermic effect of a meal was estimated (10% of daily EE). Physical activity EE was obtained by subtracting the values for resting metabolic rate and thermic effect of a meal measured with DLW from those measured with the armband. Body composition was measured with dual energy X-ray absorptiometry. Concordance between measures was evaluated by intraclass correlation, SEE, regression analysis, and Bland-Altman plots. RESULTS: Mean estimated daily EE measured with the armband was 117 kcal/d lower (2375 +/- 366 kcal/d) than that measured with DLW (2492 +/- 444 kcal/d; P < 0.01). Despite this group difference, individual comparisons between the armband and DLW were close, as evidenced by an intraclass correlation of 0.81 (P < 0.01). CONCLUSIONS: The portable armband shows reasonable concordance with DLW for measuring daily EE in free-living adults. The armband may therefore be useful to estimate daily EE. PMID- 17344496 TI - Calcium balance in 1-4-y-old children. AB - BACKGROUND: Few calcium balance data are available from young children on which to base dietary recommendations. OBJECTIVE: The objective of the study was to evaluate the relation between calcium intake and balance in healthy children aged 1-4 y consuming typical American diets. DESIGN: Subjects were assigned to a diet with nutrient intakes similar to those of their usual diet. Calcium absorption was assessed by using a dual-tracer stable-isotope technique. Endogenous fecal excretion was measured in a subset of children, and net calcium balance was calculated. RESULTS: Mean calcium intake was 551 mg/d (range: 124-983 mg/d), and mean (+/-SEM) calcium retention was 161 +/- 17 mg/d. Both linear and nonlinear modeling of balance data showed that a calcium intake of approximately 470 mg/d led to calcium retention of 140 mg/d, which is the amount that meets expected bone growth needs in children of this age. No evidence was found that calcium intakes of 800 to 900 mg/d reached the threshold intake beyond which no additional increase in calcium retention would occur. CONCLUSIONS: Bone growth needs in 1-4-y-old children following American diets are met by a daily calcium intake of approximately 470 mg/d, which suggests that the current Adequate Intake of 500 mg/d is close to the actual Estimated Average Requirement. The benefits and risks of higher calcium intakes consistent with threshold values should be evaluated in a controlled trial before those intakes could be used as a basis for dietary recommendations. PMID- 17344497 TI - Potentially modifiable determinants of vitamin D status in an older population in the Netherlands: the Hoorn Study. AB - BACKGROUND: Inadequate vitamin D status is common in many populations around the world. OBJECTIVE: The aim was to evaluate potentially modifiable determinants of vitamin D status in an older population. DESIGN: This was a cross-sectional study from a population-based cohort including 538 white Dutch men and women aged 60-87 y. Vitamin D status was assessed by plasma 25-hydroxyvitamin D [25(OH)D] concentrations. RESULTS: In the winter period, 51% of the subjects had 25(OH)D concentrations <50.0 nmol/L. Greater body fatness and less time spent on outdoor physical activity were associated with worse vitamin D status. Regular use of vitamin D-fortified margarine products [odds ratio (OR) in a comparison of intake of >or=20 g/d with none: 0.41; 95% CI: 0.20, 0.86; P for trend < 0.001], fatty fish (OR for servings of >or=2/mo versus none: 0.41; 95% CI: 0.16, 1.04; P for trend = 0.01), and vitamin D-containing supplements (OR for >or= 1/d versus none: 0.33; 95% CI: 0.17, 0.63; P for trend < 0.001) were inversely associated with vitamin D inadequacy [25(OH)D <50.0 nmol/L]. We estimated that combined use of margarine products (20 g/d), fatty fish (100 g/wk), and vitamin D supplements (>or=1/d) was associated with a 16.8 nmol/L higher 25(OH)D concentration than was the use of none of these. However, none of the participants reached these intakes for all 3 factors. CONCLUSION: Because few foods are vitamin D-fortified and the amounts of vitamin D in supplements are low, it is difficult to achieve adequate vitamin D status through increasing intakes in the Netherlands and in countries with similar policies. PMID- 17344498 TI - Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age-related macular degeneration. AB - BACKGROUND: Low dietary intakes and low plasma concentrations of lutein and zeaxanthin are associated with an increased risk of age-related macular degeneration (AMD). No studies have challenged AMD patients with a diet high in lutein and zeaxanthin. OBJECTIVE: The objective was to examine the effect of diets low or high in lutein and zeaxanthin on plasma carotenoids and their transport in AMD patients. DESIGN: Seven AMD patients and 5 control subjects were fed a low-lutein, low-zeaxanthin diet ( approximately 1.1 mg/d) for 2 wk, which was followed by a high-lutein, high-zeaxanthin diet ( approximately 11 mg/d) for 4 wk. Ten subjects continued the diet for 8 wk. Plasma and lipoprotein carotenoids were measured by HPLC. RESULTS: The high-lutein, high-zeaxanthin diet resulted in 2- to 3-fold increases in plasma concentrations of lutein and zeaxanthin and other carotenoids, except lycopene, in the AMD patients and the control subjects. With this diet, 52% of the lutein and 44% of the zeaxanthin were transported by HDL; approximately 22% of lutein and zeaxanthin was transported by LDL. Only 20-25% of alpha-carotene, beta-carotene, and lycopene was transported by HDL; 50-57% was transported by LDL. CONCLUSIONS: The AMD patients and control subjects responded similarly to a diet high in lutein and zeaxanthin; plasma carotenoid concentrations increased greatly in both groups, and the transport of carotenoids by lipoproteins was not significantly different between the groups. This finding suggests that abnormalities in the metabolism of lutein and zeaxanthin in AMD may reside in the uptake of lutein and zeaxanthin from the plasma and transport into the retina. PMID- 17344499 TI - Excentral cleavage of beta-carotene in vivo in a healthy man. AB - BACKGROUND: Excentral cleavage of beta-carotene to retinoids and apocarotenoids occurs in vitro and in animal models. Whether it occurs in humans is unclear. OBJECTIVE: We tested the hypothesis of whether humans can cleave beta-carotene excentrally. DESIGN: A healthy man was given an oral dose of all-trans [10,10',11,11'-(14)C]-beta-carotene (1.01 nmol; 100 nCi). Its fate and that of its metabolites were measured in serial plasma samples. Its fate in feces and urine was also measured over time. Selected plasma samples were spiked with reference standards of retinol, beta-apo-12'-carotenal, beta-apo-8'-carotenal, 13 cis-retinoic acid, all-trans-retinoic acid, beta-carotene-5,6-epoxide, all-trans beta-carotene, and retinyl palmitate and subjected to reverse-phase HPLC fractionation. The plasma, plasma fractions, urine, and feces were measured for (14)C with the use of accelerator mass spectrometry. RESULTS: Sixty-five percent of administered (14)C was absorbed, and 15.7% was eliminated in urine during the first 21 d after dosing. (14)C-beta-carotene and (14)C-retinyl palmitate appeared in plasma 0.25 d after the dose. (14)C-beta-carotene and (14)C-retinol both appeared at 0.5 d only. On day 3 after the dose, 2 large (14)C peaks appeared in plasma: one matched the retention time of beta-apo-8'-carotenal, and the other did not match any of the reference standards used. The delayed appearance of (14)C-beta-apo-8'-carotenal in plasma suggests that the excentral cleavage occurred after the (14)C-beta-apo-8'-carotene was absorbed into the body. CONCLUSION: These data suggest that excentral cleavage of ingested beta-carotene occurs in vivo in humans. Confirmation of that possibility and further study to identify and characterize additional metabolites are needed. PMID- 17344500 TI - Iron treatment normalizes cognitive functioning in young women. AB - BACKGROUND: Evidence suggests that brain iron deficiency at any time in life may disrupt metabolic processes and subsequently change cognitive and behavioral functioning. Women of reproductive age are among those most vulnerable to iron deficiency and may be at high risk for cognitive alterations due to iron deficiency. OBJECTIVE: We aimed to examine the relation between iron status and cognitive abilities in young women. DESIGN: A blinded, placebo-controlled, stratified intervention study was conducted in women aged 18-35 y of varied iron status who were randomly assigned to receive iron supplements or a placebo. Cognition was assessed by using 8 cognitive performance tasks (from Detterman's Cognitive Abilities Test) at baseline (n = 149) and after 16 wk of treatment (n = 113). RESULTS: At baseline, the iron-sufficient women (n = 42) performed better on cognitive tasks (P = 0.011) and completed them faster (P = 0.038) than did the women with iron deficiency anemia (n = 34). Factors representing performance accuracy and the time needed to complete the tasks by the iron-deficient but nonanemic women (n = 73) were intermediate between the 2 extremes of iron status. After treatment, a significant improvement in serum ferritin was associated with a 5-7-fold improvement in cognitive performance, whereas a significant improvement in hemoglobin was related to improved speed in completing the cognitive tasks. CONCLUSIONS: Iron status is a significant factor in cognitive performance in women of reproductive age. Severity of anemia primarily affects processing speed, and severity of iron deficiency affects accuracy of cognitive function over a broad range of tasks. Thus, the effects of iron deficiency on cognition are not limited to the developing brain. PMID- 17344501 TI - Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. AB - BACKGROUND: Vitamin D deficiency and asthma are common at higher latitudes. Although vitamin D has important immunologic effects, its relation with asthma is unknown. OBJECTIVE: We hypothesized that a higher maternal intake of vitamin D during pregnancy is associated with a lower risk of recurrent wheeze in children at 3 y of age. DESIGN: The participants were 1194 mother-child pairs in Project Viva-a prospective prebirth cohort study in Massachusetts. We assessed the maternal intake of vitamin D during pregnancy from a validated food-frequency questionnaire. The primary outcome was recurrent wheeze, ie, a positive asthma predictive index (>or=2 wheezing attacks among children with a personal diagnosis of eczema or a parental history of asthma). RESULTS: The mean (+/-SD) total vitamin D intake during pregnancy was 548 +/- 167 IU/d. By age 3 y, 186 children (16%) had recurrent wheeze. Compared with mothers in the lowest quartile of daily intake (median: 356 IU), those in the highest quartile (724 IU) had a lower risk of having a child with recurrent wheeze [odds ratio (OR): 0.39; 95% CI: 0.25, 0.62; P for trend < 0.001]. A 100-IU increase in vitamin D intake was associated with lower risk (OR: 0.81; 95% CI: 0.74, 0.89), regardless of whether vitamin D was from the diet (OR: 0.81; 95% CI: 0.69, 0.96) or supplements (OR: 0.82; 95% CI: 0.73, 0.92). Adjustment for 12 potential confounders, including maternal intake of other dietary factors, did not change the results. CONCLUSION: In the northeastern United States, a higher maternal intake of vitamin D during pregnancy may decrease the risk of recurrent wheeze in early childhood. PMID- 17344502 TI - Maternal smoking is associated with decreased 5-methyltetrahydrofolate in cord plasma. AB - BACKGROUND: Maternal-fetal folate transport via the placenta has been shown to be concentrative. Exposure to cigarette smoke is associated with decreased maternal folate status through altered dietary intakes and possibly through nondietary mechanisms such as increased folate turnover. The effect of maternal smoking on fetal folate status has not been documented. OBJECTIVE: The objective was to determine the effect of maternal smoking on plasma 5-methyltetrahydrofolic acid (5-MTHFA) concentrations in umbilical cord blood. DESIGN: African American women were recruited from an antenatal clinic in Detroit, MI. Plasma 5-MTHFA concentrations were measured in maternal-umbilical cord pairings (n = 58). The participants completed a structured interview to determine demographic characteristics, including smoking. RESULTS: Concentrations of 5-MTHFA were significantly higher in venous cord plasma (16.8 +/- 7.5 ng/mL) than in maternal plasma (13.0 +/- 7.5 ng/mL) but remained associated (r = 0.60, P < 0.001) with each other. Cigarettes smoked by the mothers was negatively associated (r = 0.31, P = 0.019) with venous cord 5-MTHFA concentrations and remained so after control for maternal plasma 5-MTHFA and other variables. Venous cord plasma 5 MTHFA was significantly lower in smoking (15.1 +/- 7.6 ng/mL; n = 32) than in nonsmoking (19.0 +/- 7.0 ng/mL; n = 26) mothers. CONCLUSIONS: Cord plasma 5-MTHFA concentrations were elevated relative to maternal blood, as expected, because the placenta is capable of concentrative folate transport to the fetus. The negative effect of maternal smoking on infant, but not on maternal, 5-MTHFA status indicates that maternal smoking may impair folate transport to the fetus. PMID- 17344503 TI - n-3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO2 Study. AB - BACKGROUND: Knowledge of the influence of nutritional intake on bone health is limited. Polyunsaturated fatty acids have been suggested to influence bone growth and modeling in humans, although data are sparse. OBJECTIVE: The objective was to investigate the role of fatty acids in bone accumulation and the attainment of peak bone mass in young men. DESIGN: The cohort studied consisted of 78 healthy young men with a mean age of 16.7 y at baseline. Bone mineral density (BMD; in g/cm(2)) of total body, hip, and spine was measured at baseline and at 22 and 24 y of age. Fatty acid concentrations were measured in the phospholipid fraction in serum at 22 y of age. RESULTS: Concentrations of n-3 fatty acids were positively associated with total BMD (r = 0.27, P = 0.02) and spine BMD (r = 0.25, P = 0.02) at 22 y of age. A positive correlation between n-3 fatty acid concentrations and the changes in BMD at the spine (r = 0.26, P = 0.02) was found between 16 and 22 y of age. Concentrations of docosahexaenoic acid (DHA, 22:6n-3) were positively associated with total BMD (r = 0.32, P = 0.004) and BMD at the spine (r = 0.30, P = 0.008) at 22 y of age. A positive correlation was also found between DHA concentrations and the changes in BMD at the spine (r = 0.26, P = 0.02) between 16 and 22 y of age. CONCLUSION: The results showed that n-3 fatty acids, especially DHA, are positively associated with bone mineral accrual and, thus, with peak BMD in young men. PMID- 17344504 TI - Altered postprandial glucose, insulin, leptin, and ghrelin in liver cirrhosis: correlations with energy intake and resting energy expenditure. AB - BACKGROUND: Liver cirrhosis is associated with reduced energy intake and increased resting energy expenditure. OBJECTIVE: We aimed to investigate the possible role of glucose, insulin, leptin, and ghrelin in the pathogenesis of these alterations. DESIGN: Nutritional status, energy intake, resting energy expenditure, and fasting glucose, insulin, and leptin were assessed in 31 patients with cirrhosis. Postprandial glucose, insulin, C-peptide, leptin, and ghrelin responses were studied in a subgroup of patients after a standard meal. Ten healthy subjects served as controls. RESULTS: Patients with cirrhosis had a lower energy intake (P < 0.05), higher resting energy expenditure (P < 0.05), higher fasting leptin (P < 0.05), and higher insulin resistance (P < 0.001) than did the healthy control subjects. In the patients with cirrhosis, fasting leptin was negatively correlated with resting energy expenditure (r = -0.38, P < 0.05) but not with energy intake. In control subjects, leptin was negatively correlated with energy intake (r = -0.72, P < 0.05) but not with resting energy expenditure. The patients with cirrhosis had higher postprandial glucose (P < 0.001) and lower ghrelin (P < 0.05) concentrations at 4 h postprandially than did the control subjects. The increase in ghrelin from its minimal postmeal value to 4 h postmeal was negatively correlated (r = -0.66, P = 0.014) with weight loss in the patients with cirrhosis. Energy intake was negatively correlated (r = -0.42, P < 0.01) with the postprandial increase in glucose. CONCLUSIONS: In cirrhosis, altered postprandial glucose and ghrelin are associated with reduced energy intake and weight loss, respectively, and the effects of leptin on energy intake and expenditure seem to be altered. Insulin resistance might be involved in these altered postprandial responses. PMID- 17344505 TI - Effects of probiotic therapy in critically ill patients: a randomized, double blind, placebo-controlled trial. AB - BACKGROUND: Multiple organ dysfunction syndrome (MODS) is a major cause of mortality in intensive care units. A breakdown in gut barrier function and immune dysfunction are associated with the onset of MODS. Probiotic bacteria have been shown to modulate intestinal barrier and immune function. OBJECTIVE: This study assessed the efficacy of a probiotic compound in a viable and nonviable formulation in modulating intestinal permeability and immune function and preventing the onset of MODS in patients in the intensive care unit. DESIGN: A double-blind, randomized controlled trial was conducted in the intensive care unit of a tertiary care teaching hospital. Twenty-eight critically ill patients admitted to the intensive care unit were randomly assigned to receive 1 of 3 treatments daily for 7 d: 1) placebo, 2) viable probiotics, or 3) equivalent probiotic sonicates. MODS scores and systemic concentrations of immunoglobulin (Ig) A and IgG were measured on days -1, 4, and 7, and intestinal permeability measurements were taken daily. RESULTS: The patients responded to viable probiotics with a significantly larger increase in systemic IgA and IgG concentrations than in the patients who received placebo or sonicates (P < 0.05). MODS scores were not significantly affected by probiotic treatment. Over the study period, intestinal permeability decreased in most patients. CONCLUSION: Patients receiving viable probiotics show a greater enhancement in immune activity than do patients receiving either placebo or probiotic bacterial sonicates. PMID- 17344506 TI - Arachidonic acid-and docosahexaenoic acid-enriched formulas modulate antigen specific T cell responses to influenza virus in neonatal piglets. AB - BACKGROUND: Whereas the immunomodulatory effects of feeding either arachidonic acid (AA) or docosahexaenoic acid (DHA) separately have been previously investigated, little is known about the immunomodulatory efficacy of AA or DHA when they are fed in combination as infant formula ingredients. OBJECTIVE: The objective of this study was to investigate the ability of AA- and DHA(AA/DHA) enriched infant formula to modulate immune responses in the neonate in response to an inactivated influenza virus vaccine. DESIGN: Neonatal piglets (n = 48) were weaned on day 2 of age and distributed into 16 blocks of 3 littermate piglets each. Within each block, piglets were randomly assigned to a control formula, AA/DHA-enriched formula (0.63% AA and 0.34% DHA), or sow milk for 30 d. On day 9, 8 blocks of piglets were immunized with an inactivated influenza virus vaccine. On days 0, 9, 16, 23, and 30 after weaning, we measured influenza virus-specific T cell proliferation and phenotype of T subsets in peripheral blood. A delayed type hypersensitivity reaction test was administered on day 28. Cytokine messenger RNA expression was determined by quantitative real time reverse transcriptase-polymerase chain reaction on day 30. RESULTS: The influenza virus specific CD4(+) and CD8(+) T cell ex vivo lymphoproliferative responses were significantly lower on day 23 after immunization in piglets receiving dietary AA/DHA supplementation and sow milk than in those receiving the unsupplemented control formula. The immunomodulatory effects of AA/DHA-enriched formulas were consistent with up-regulation of interleukin 10 in peripheral blood mononuclear cells. CONCLUSION: Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism. PMID- 17344507 TI - Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. AB - BACKGROUND: Zinc deficiency, cell-mediated immune dysfunction, susceptibility to infections, and increased oxidative stress have been observed in elderly subjects (ie, those >55 y old). Zinc is an effective antiinflammatory and antioxidant agent. OBJECTIVES: The primary objective was to determine the effect of zinc on the incidence of total infections in healthy elderly subjects. The secondary objective was to determine the effect of zinc on cytokines and oxidative stress markers. DESIGN: A randomized, double-blind, placebo-controlled trial of zinc supplementation was conducted in elderly subjects. Fifty healthy subjects of both sexes aged 55-87 y and inclusive of all ethnic groups were recruited for this study from a senior center. The zinc-supplemented group received zinc gluconate (45 mg elemental Zn/d) orally for 12 mo. Incidence of infections during the supplementation period was documented. The generation of inflammatory cytokines, T helper 1 and T helper 2 cytokines, and oxidative stress markers and the plasma concentrations of zinc were measured at baseline and after supplementation. RESULTS: Compared with a group of younger adults, at baseline the older subjects had significantly lower plasma zinc, higher ex vivo generation of inflammatory cytokines and interleukin 10, and higher plasma oxidative stress markers and endothelial cell adhesion molecules. The incidence of infections and ex vivo generation of tumor necrosis factor alpha and plasma oxidative stress markers were significantly lower in the zinc-supplemented than in the placebo group. Plasma zinc and phytohemagglutin-induced interleukin 2 mRNA in isolated mononuclear cells were significantly higher in the zinc-supplemented than in the placebo group. CONCLUSIONS: After zinc supplementation, the incidence of infections was significantly lower, plasma zinc was significantly higher, and generation of tumor necrosis factor alpha and oxidative stress markers was significantly lower in the zinc-supplemented than in the placebo group. PMID- 17344508 TI - Low birth weight is associated with altered immune function in rural Bangladeshi children: a birth cohort study. AB - BACKGROUND: Low birth weight is generally an outcome of a fetal insult or nutritional insufficiency. Recent studies have shown that such exposure early in life may have long-term implications for later immunocompetence and susceptibility to infectious diseases. OBJECTIVE: We aimed to investigate the effect of birth weight on immune function in preschool-age children. DESIGN: A birth cohort cross-sectional study was conducted in children (n = 132) aged 60.8 +/- 0.32 mo who were born in Matlab, a rural area of Bangladesh, and whose weight and length were measured within 72 h of birth. The outcome measures were thymopoiesis, T cell turnover, acute phase response, and percentage of lymphocytes. RESULTS: Children born with low birth weight (<2500 g; LBW group, n = 66) had significantly higher concentrations of T cell receptor excision circles in peripheral blood mononuclear cells-a biomarker for thymopoiesis-and significantly higher serum bactericidal activity and C-reactive protein concentrations than did children born with normal birth weight (>or=2500 g; NBW group, n = 66) (P < 0.05 for both). The LBW group children had significantly lower concentrations of interleukin 7 in plasma (P = 0.02), shorter telomere length in peripheral blood mononuclear cells (P = 0.02), and a lower percentage of CD3 T cells (P = 0.06) than did the NBW group children. CONCLUSIONS: Greater peripheral T cell turnover (shorter telomeres and lower CD3 concentrations) due to immune activation (elevated C-reactive protein concentrations and bactericidal activity) may have resulted in a greater need for replenishment from the thymus (higher T cell receptor excision circles); these events may cause lower immune functional reserve in preschool-age children born with LBW. Thus, LBW has implications for immunocompetence and increased vulnerability to infectious diseases in later life. PMID- 17344509 TI - Maternal vitamin D intake during pregnancy and early childhood wheezing. AB - BACKGROUND: Maternal intake of vitamin D in pregnancy is a potentially modifiable but understudied risk factor for the development of asthma in children. OBJECTIVE: We investigated whether maternal vitamin D intake in pregnancy is associated with decreased risks of wheezing symptoms in young children. DESIGN: Subjects were from a birth cohort recruited in utero with the primary objective of identifying associations between maternal diet during pregnancy and asthma and allergies in children. A random sample of 2000 healthy pregnant women was recruited while attending antenatal clinics at the Aberdeen Maternity Hospital, Scotland, at approximately 12 wk gestation. Maternal vitamin D intake was ascertained from a food-frequency questionnaire completed at 32 wk of gestation. The main outcome measures were wheezing symptoms, spirometry, bronchodilator response, atopic sensitization, and exhaled nitric oxide at 5 y. RESULTS: Respiratory details through 5 y and maternal food-frequency-questionnaire data were available for 1212 children. In models adjusted for potential confounders, including the children's vitamin D intake, a comparison of the highest and lowest quintiles of maternal total vitamin D intake conferred lower risks for ever wheeze [odds ratio (OR): 0.48; 95% CI: 0.25, 0.91], wheeze in the previous year (OR: 0.35; 95% CI: 0.15, 0.83), and persistent wheeze (OR: 0.33; 95% CI: 0.11, 0.98) in 5-y-old children. In addition, lower maternal total vitamin D intakes in pregnancy were also associated with decreased bronchodilator response (P = 0.04). No associations were observed between maternal vitamin D intakes and spirometry or exhaled nitric oxide concentrations. CONCLUSION: Increasing maternal vitamin D intakes during pregnancy may decrease the risk of wheeze symptoms in early childhood. PMID- 17344510 TI - Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. AB - BACKGROUND: Increased awareness of the importance of vitamin D to health has led to concerns about the prevalence of hypovitaminosis D in many parts of the world. OBJECTIVES: We aimed to determine the prevalence of hypovitaminosis D in the white British population and to evaluate the influence of key dietary and lifestyle risk factors. DESIGN: We measured 25-hydroxyvitamin D [25(OH)D] in 7437 whites from the 1958 British birth cohort when they were 45 y old. RESULTS: The prevalence of hypovitaminosis D was highest during the winter and spring, when 25(OH)D concentrations <25, <40, and <75 nmol/L were found in 15.5%, 46.6%, and 87.1% of participants, respectively; the proportions were 3.2%, 15.4%, and 60.9%, respectively, during the summer and fall. Men had higher 25(OH)D concentrations, on average, than did women during the summer and fall but not during the winter and spring (P = 0.006, likelihood ratio test for interaction). 25(OH)D concentrations were significantly higher in participants who used vitamin D supplements or oily fish than in those who did not (P < 0.0001 for both) but were not significantly higher in participants who consumed vitamin D-fortified margarine than in those who did not (P = 0.10). 25(OH)D concentrations <40 nmol/L were twice as likely in the obese as in the nonobese and in Scottish participants as in those from other parts of Great Britain (ie, England and Wales) (P < 0.0001 for both). CONCLUSION: Prevalence of hypovitaminosis D in the general population was alarmingly high during the winter and spring, which warrants action at a population level rather than at a risk group level. PMID- 17344511 TI - Anthropometric measures in middle age after exposure to famine during gestation: evidence from the Dutch famine. AB - BACKGROUND: Few studies in humans have related maternal undernutrition to the size of the adult offspring. OBJECTIVE: The objective was to assess whether reductions in food intake by pregnant women during the Dutch famine of 1944-1945 were related to offspring length, weight, and indexes of adiposity in middle age. DESIGN: We recruited 1) exposed persons born in western Netherlands between January 1945 and March 1946 whose mothers experienced famine during or immediately preceding pregnancy, 2) unexposed persons born in the same 3 institutions during 1943 or 1947 whose mothers did not experience famine during this pregnancy, and 3) unexposed same-sex siblings of persons in series 1 or 2. Anthropometric measurements (n = 427 males and 529 females) were obtained between 2003 and 2005. We defined 4 windows of gestational exposure (by ordinal weeks 1 10, 11-20, 21-30, and 31 through delivery) on the basis of exposure to a ration of <900 kcal/d during the whole 10-wk interval. RESULTS: Exposure to reduced rations was associated with increased weight and greater indexes of fat deposition at several tissue sites in women but not in men (P for interaction <0.01). Measures of length and linear proportion were not associated with exposure to famine. CONCLUSION: Reduced food availability may lead to increased adiposity later in life in female offspring. PMID- 17344512 TI - Prospective study of intake of fruit, vegetables, and carotenoids and the risk of adult glioma. AB - BACKGROUND: Nutrients in dietary fruit and vegetables have been hypothesized to lower the risk of glioma by reducing the endogenous formation of N-nitroso compounds. Studies examining fruit and vegetable consumption and brain tumors have relied on case-control study designs, with one exception, and results have been inconsistent. OBJECTIVE: We prospectively examined the relation between consumption of fruit and vegetables (and specifically carotenoids) and the risk of glioma among men and women in 3 large US cohort studies: the Health Professionals Follow-Up Study (HPFS), the Nurses' Health Study I (NHS I), and NHS II. DESIGN: Dietary intake was assessed by food-frequency questionnaires obtained at baseline and updated every 4 y through 2002 (HPFS and NHS I) or 2003 (NHS II). We identified 296 incident adult gliomas during 3 669 589 person-years of follow up. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% CIs between intake of fruit, vegetables, and carotenoids and glioma risk, with adjustment for age and total caloric intake. RESULTS: Updated average consumption of total fruit and vegetables was not significantly associated with glioma risk in the men and women (pooled multivariate RR in a comparison of the highest with the lowest quintile: 1.12; 95% CI: 0.74, 1.69). Other fruit and vegetable subgroups, individual fruit and vegetables, and 5 major carotenoids were not significantly associated with risk of glioma. CONCLUSION: Our findings suggest that fruit, vegetable, and carotenoid consumption is not likely associated strongly with the risk of adult glioma. PMID- 17344513 TI - Zinc during and in convalescence from diarrhea has no demonstrable effect on subsequent morbidity and anthropometric status among infants <6 mo of age. AB - BACKGROUND: Preventing illness and improving growth in the first 6 mo of life is critical to reducing infant mortality. Zinc given for 14 d at the start of diarrhea has been shown to decrease the incidence and prevalence of diarrhea and pneumonia and improve growth in the 2-3 mo after, but no trial has been done in infants <6 mo of age. OBJECTIVE: This study sought to assess the effect of 14 d of zinc supplementation on subsequent morbidity and growth among infants 1-5 mo of age living in Pakistan, India, and Ethiopia. DESIGN: Infants with acute diarrhea were randomly assigned to receive zinc (10 mg/d; n = 538) or placebo (n = 536) for 2 wk. Weekly follow-up visits were conducted for 8 wk after the diarrhea episode. Incidence and prevalence of diarrhea and prevalence of respiratory infections including pneumonia were compared between the groups. Changes in weight, length, and corresponding z scores during the 8 wk of follow up were also compared. RESULTS: One thousand seventy-four infants were enrolled at the start of follow-up. The groups did not differ significantly in the proportion of infants with at least one episode of diarrhea or respiratory infections. Infants who received zinc had more days of diarrhea (rate ratio = 1.20) than did the infants who received placebo. The groups had similar prevalences of pneumonia and overall respiratory infections. No significant differences in the mean changes in weight-for-age, length-for-age, and weight-for length z scores were observed between the groups overall or in stratified analyses. CONCLUSION: Young infants do not appear to benefit from 2 wk of zinc, unlike what has been observed among older children. PMID- 17344514 TI - Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. AB - BACKGROUND: Dietary flavonoids may have beneficial cardiovascular effects in human populations, but epidemiologic study results have not been conclusive. OBJECTIVE: We used flavonoid food composition data from 3 recently available US Department of Agriculture databases to improve estimates of dietary flavonoid intake and to evaluate the association between flavonoid intake and cardiovascular disease (CVD) mortality. DESIGN: Study participants were 34 489 postmenopausal women in the Iowa Women's Health Study who were free of CVD and had complete food-frequency questionnaire information at baseline. Intakes of total flavonoids and 7 subclasses were categorized into quintiles, and food sources were grouped into frequency categories. Proportional hazards rate ratios (RR) were computed for CVD, coronary heart disease (CHD), stroke, and total mortality after 16 y of follow-up. RESULTS: After multivariate adjustment, significant inverse associations were observed between anthocyanidins and CHD, CVD, and total mortality [RR (95% CI) for any versus no intake: 0.88 (0.78, 0.99), 0.91 (0.83, 0.99), and 0.90 (0.86, 0.95)]; between flavanones and CHD [RR for highest quintile versus lowest: 0.78 (0.65, 0.94)]; and between flavones and total mortality [RR for highest quintile versus lowest: 0.88 (0.82, 0.96)]. No association was found between flavonoid intake and stroke mortality. Individual flavonoid-rich foods associated with significant mortality reduction included bran (added to foods; associated with stroke and CVD); apples or pears or both and red wine (associated with CHD and CVD); grapefruit (associated with CHD); strawberries (associated with CVD); and chocolate (associated with CVD). CONCLUSION: Dietary intakes of flavanones, anthocyanidins, and certain foods rich in flavonoids were associated with reduced risk of death due to CHD, CVD, and all causes. PMID- 17344515 TI - Dietary patterns, insulin resistance, and prevalence of the metabolic syndrome in women. AB - BACKGROUND: Although individual foods and nutrients have been associated with the metabolic syndrome, whether dietary patterns identified by factor analysis are also associated with this syndrome is not known. OBJECTIVE: We aimed to evaluate the association of major dietary patterns characterized by factor analysis with insulin resistance and the metabolic syndrome among women. DESIGN: Usual dietary intakes were assessed in a cross-sectional study of 486 Tehrani female teachers aged 40-60 y. Anthropometric and blood pressure measurements were performed, and fasting blood samples were taken for biomarker assessment. The metabolic syndrome was defined according to Adult Treatment Panel III guidelines, and insulin resistance was defined as the highest quartile of the homeostasis model assessment scores. RESULTS: We identified 3 major dietary patterns by factor analysis: the healthy dietary pattern, the Western dietary pattern, and the traditional dietary pattern. After control for potential confounders, subjects in the highest quintile of healthy dietary pattern scores had a lower odds ratio for the metabolic syndrome (odds ratio: 0.61; 95% CI: 0.30, 0.79; P for trend < 0.01) and insulin resistance (0.51; 0.24, 0.88; P for trend < 0.01) than did those in the lowest quintile. Compared with those in the lowest quintile, women in the highest quintile of Western dietary pattern scores had greater odds for the metabolic syndrome (1.68; 1.10, 1.95; P for trend < 0.01) and insulin resistance (1.26; 1.00, 1.78; P for trend < 0.01). Higher consumption of traditional dietary pattern was significantly associated only with abnormal glucose homeostasis (1.19; 1.04, 1.59; P < 0.05). CONCLUSION: Significant associations exist between dietary patterns identified by factor analysis, the metabolic syndrome, and insulin resistance. PMID- 17344516 TI - n-3 Fatty acids and the endocannabinoid system. PMID- 17344517 TI - alpha-Linolenic acid and fish oil n-3 fatty acids and cardiovascular disease risk. PMID- 17344518 TI - New horizons for glycemic index research. PMID- 17344519 TI - Uterine contractility evaluated on cine magnetic resonance imaging. AB - The inherent contractility of the uterus has attracted concern of researchers and exhibits two known patterns of contraction. One is focal and sporadic bulging of the myometrium, and the other is rhythmic and subtle stripping movement in the subendometrial myometrium, known as uterine peristalsis. Recent development in the ultrafast magnetic resonance imaging (MRI) techniques has enabled us to observe these uterine contractions directly and noninvasively. Although the mechanisms and relationship of these two kinds of myometrial contractions and their relations to age, pharmaceutical administration such as oral contraceptives (OCs), and a variety of gynecologic and obstetrical problems are still under debate, cine MRI can be applied for directly monitoring changes of the uterus related to important uterine functions such as fertility and menstrual problems. PMID- 17344520 TI - Nuclear labeling of Coccidioides posadasii with green fluorescent protein. AB - Coccidioidomycosis is a mild to life-threatening disease in otherwise healthy humans and other mammals caused by the fungus Coccidioides spp. Understanding the development of the unique dimorphic life cycle of Coccidioides spp. and its role in pathogenesis has been an area of research focus. However, nuclear behavior during the saprobic and parasitic life cycle has not been studied intensively. In this study, green fluorescent protein (GFP) was fused to histone H1 and introduced into Coccidioides posadasii (C. posadasii) strain Silveira to monitor the nuclear behavior of the fungus during the saprobic and parasitic stages of the life cycle. We constructed an Agrobacterium tumefaciens-mediated transformation (ATMT) vector that had in its T-DNA region a hygromycin-resistance gene as well as the fused histone H1-GFP gene under the control of the histone H3 promoter of C. posadasii. More than 30 hygromycin-resistant transformants were obtained and 23 were purified to homozygosity through multiple passages of the original transformants on hygromycin-containing media. One strain (VFC1420) transformed with a single copy of the fusion histone H1-GFP gene was selected for cytological studies. Strong nuclear-localized GFP signals were observed in arthroconidia, hyphae, as well as in spherules and endospores developed in vitro. Thus GFP can be used to study the expression pattern of potential virulence genes identified in serial analysis of gene expression (SAGE) or expressed sequence tags (EST) libraries, and could be a useful tool to monitor disease development in the murine model. PMID- 17344521 TI - Deep solitary brain mass in a four-month-old male with disseminated coccidioidomycosis: case report. AB - Parenchymal brain involvement from disseminated coccidioidomycosis occurs rarely and there are few documented pediatric cases. We report a four-month-old male infant with a cerebellar lesion seen in the brain on computed tomography (CT). Coccidioides immitis (C. immitis) grew on bronchoscopic fluid samples and serum titers to C. immitis were 1:1024. Antifungal treatment was initiated and after 3 months, CT scans demonstrated brain mass resolution and serum titers were decreased. PMID- 17344522 TI - Reward-related responses in the human striatum. AB - Much of our knowledge of how reward information is processed in the brain comes from a rich animal literature. Recently, the advancement of neuroimaging techniques has allowed researchers to extend such investigations to the human brain. A common finding across species and methodologies is the involvement of the striatum, the input structure of the basal ganglia, in a circuit responsible for mediating goal-directed behavior. Central to this idea is the role of the striatum in the processing of affective stimuli, such as rewards and punishments. The goal of this article is to probe the human reward circuit, specifically the striatum and its subdivisions, with an emphasis on how the affective properties of outcomes or feedback influence the underlying neural activity and subsequent decision making. Discussion will first focus on anatomical and functional considerations regarding the striatum that have emerged from animal models. The rest of the article will center on how human neuroimaging studies map to findings from the animal literature, and how more recently, this research can be extended into the social and economic domains. PMID- 17344523 TI - Molecular cloning and expression of a cDNA encoding a Coccidioides posadasii Cu,Zn superoxide dismutase identified by proteomic analysis of the coccidioidal T27K vaccine. AB - Previous studies have demonstrated that the coccidioidal T27K vaccine preparation is protective in mice against respiratory challenge using Coccidioides posadasii (C. posadasii) arthroconidia. Proteomic methods have been employed to define the molecular components within the vaccine. This method has led to the identification of novel and previously uncharacterized coccidioidal proteins including a Cu,Zn superoxide dismutase. A two-dimensional gel of the T27K vaccine was run and spots were excised for mass spectrometric analysis. One peptide was obtained from the T27K gel that matched a TIGR C. posadasii 2.0 gene index tentative consensus sequence, TC1072, which is similar to fungal Cu,Zn superoxide dismutase. Activity assays performed with native PAGE gels of the T27K vaccine showed that the vaccine contains superoxide dismutase. The cDNA encoding the enzyme has been cloned and sequenced and expressed as a recombinant protein. PMID- 17344524 TI - Experimental animal models of coccidioidomycosis. AB - Experimental models of coccidioidomycosis performed using various laboratory animals have been, and remain, a critical component of elucidation and understanding of the pathogenesis and host resistance to infection with Coccidioides spp., as well as to development of more efficacious antifungal therapies. The general availability of genetically defined strains, immunological reagents, ease of handling, and costs all contribute to the use of mice as the primary laboratory animal species for models of this disease. Five types of murine models are studied and include primary pulmonary disease, intraperitoneal with dissemination, intravenous infection emulating systemic disease, and intracranial or intrathecal infection emulating meningeal disease. Each of these models has been used to examine various aspects of host resistance, pathogenesis, or antifungal therapy. Other rodent species, such as rat, have been used much less frequently. A rabbit model of meningeal disease, established by intracisternal infection, has proven to model human meningitis well. This model is useful in studies of host response, as well as in therapy studies. A variety of other animal species including dogs, primates, and guinea pigs have been used to study host response and vaccine efficacy. However, cost and increased needs of animal care and husbandry are limitations that influence the use of the larger animal species. PMID- 17344525 TI - Coccidioidomycosis infection in a predominantly Hispanic population. AB - In Texas there are limited data on the epidemiology of coccidioidomycosis. Our goal is to determine the prevalence of coccidioidomycosis in a county hospital in El Paso, Texas. The charts of all patients with coccidioidomycosis admitted to the hospital in the past 9 years was retrospectively reviewed statistical analysis performed. Forty-one cases were identified, giving a prevalence of 3.2 cases per 10,000 discharges. Pneumonic consolidation occurred in 14 (44%), miliary pattern in 6 (19%) and cavitation in 6 (19%) cases. Pulmonary involvement occurred in 32 patients (78%) and meningeal involvement in 3 patients. Six patients had disseminated disease. The mortality rate was higher with disseminated disease (50% compared to 3.6%, P = 0.04). Four had concomitant pulmonary tuberculosis. Diabetes mellitus was found in 17 patients (41.4%), followed by HIV infection in 15 (36.5%). Patients with HIV had a higher incidence of disseminated disease (36.4% vs. 0%, P = 0.01). Four patients died, and the risk of death was increased in disseminated disease (P < 0.05). Coccidioiomycosis is not as frequent in El Paso, and for that matter in Texas, as in other states, but still has to be taken into consideration both in HIV and in diabetic patients. PMID- 17344526 TI - Adding prediction risk to the theory of reward learning. AB - This article analyzes the simple Rescorla-Wagner learning rule from the vantage point of least squares learning theory. In particular, it suggests how measures of risk, such as prediction risk, can be used to adjust the learning constant in reinforcement learning. It argues that prediction risk is most effectively incorporated by scaling the prediction errors. This way, the learning rate needs adjusting only when the covariance between optimal predictions and past (scaled) prediction errors changes. Evidence is discussed that suggests that the dopaminergic system in the (human and nonhuman) primate brain encodes prediction risk, and that prediction errors are indeed scaled with prediction risk (adaptive encoding). PMID- 17344527 TI - Coccidioides niches and habitat parameters in the southwestern United States: a matter of scale. AB - To determine habitat attributes and processes suitable for the growth of Coccidioides, soils were collected from sites in Arizona, California, and Utah where Coccidioides is known to have been present. Humans or animals or both have been infected by Coccidioides at all of the sites. Soil variables considered in the upper 20 cm of the soil profile included pH, electrical conductivity, salinity, selected anions, texture, mineralogy, vegetation types and density, and the overall geomorphologic and ecological settings. Thermometers were buried to determine the temperature range in the upper part of the soil where Coccidioides is often found. With the exception of temperature regimes and soil textures, it is striking that none of the other variables or group of variables that might be definitive are indicative of the presence of Coccidioides. Vegetation ranges from sparse to relatively thick cover in lower Sonoran deserts, Chaparral-upper Sonoran brush and grasslands, and Mediterranean savannas and forested foothills. No particular grass, shrub, or forb is definitive. Material classified as very fine sand and silt is abundant in all of the Coccidioides-bearing soils and may be their most common shared feature. Clays are not abundant (less than 10%). All of the examined soil locations are noteworthy as generally 50% of the individuals who were exposed to the dust or were excavating dirt at the sites were infected. Coccidioides has persisted in the soil at a site in Dinosaur National Monument, Utah for 37 years and at a Tucson, Arizona site for 41 years. PMID- 17344528 TI - Contextual control of choice performance: behavioral, neurobiological, and neurochemical influences. AB - An important aspect of decision making is the ability of responses to be controlled by different cues in different situations or contexts, especially when there is conflict between alternative responses or actions.Recently, a context dependent biconditional task has been developed for rats that mimic some aspects of response conflict seen in human cognitive paradigms, such as the Stroop task. In this task, contextual cues are used to disambiguate conflicting response information provided by audiovisual compound stimuli. Here we review current findings that investigate some of the behavioral, neurobiological, and neurochemical mechanisms that underlie this use of contextual or task-setting information to resolve response conflict, and discuss future ways in which this research can be extended. PMID- 17344529 TI - The public health need and present status of a vaccine for the prevention of coccidioidomycosis. AB - Although the epidemiology of coccidioidomycosis has been well described, there is a paucity of recent data on the public health burden associated with this disease. Accordingly, California's Inpatient Hospital Discharge Data Set from 1997 to 2002 was used to calculate the incidence of hospitalization for coccidioidomycosis by county, year, age, race, ethnicity, and gender. The overall finding that coccidioidomycosis has a significant impact in endemic areas supports the conclusion that the need for a preventive vaccine is great. Investigators of the Valley Fever Vaccine Project (VFVP) have successfully identified a number of recombinant coccidioidal protein antigens and two attenuated mutant strains that have been evaluated as vaccines, demonstrating protective responses in murine models. Efforts to select and develop a vaccine for human clinical trials are in progress. PMID- 17344530 TI - Coccidioidomycosis: changing perceptions and creating opportunities for its control. AB - The perceptions of coccidioidomycosis as a medical problem has undergone sequential and dramatic metamorphoses since its first description more than a century ago. First thought to be rare and lethal, coccidioidomycosis was subsequently found to be common and often mild. During World War II, its overall impact upon large populations came sharply into focus and the consequences for public health became clearer. Early treatments had significant limitations and toxicities, and therefore treatment of coccidioidomycosis was reserved for only the sickest patients. Since then, safer oral therapies have become commonplace. Despite their availability, there has been no investigation of their use in the less severe and much more common early infections. Even newer drugs such as nikkomycin Z, which might actually cure infections, until very recently have had trouble finding a sponsor to move it through clinical trials. Perceptions once formed by the understanding of coccidioidomycosis as a medical problem now appear to hinder the future study of newer therapeutic opportunities. It is suggested in this review that it is time to revisit and possibly change these perceptions if we are to improve our care of patients. PMID- 17344531 TI - The application of proteomic techniques to fungal protein identification and quantification. AB - The number of sequenced genomes has increased rapidly in the last few years, supporting a revolution in bioinformatics that has been leveraged by scientists seeking to analyze the proteomes of numerous biological systems. The primary technique employed for the identification of peptides and proteins from biological sources is mass spectrometry (MS). This analytical process is usually in the form of whole-protein analysis (termed "top-down" proteomics) or analysis of enzymatically produced peptides (known as the "bottom-up" approach). This article will focus primarily on the more common bottom-up proteomics to include topics such as sample preparation, separation strategies, MS instrumentation, data analysis, and techniques for protein quantification. Strategies for preparation of samples for proteomic analysis, as well as tools for protein and peptide separation will be discussed. A general description of common MS instruments along with tandem mass spectrometry (MS/MS) will be given. Different methodologies of sample ionization including matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) will be discussed. Data analysis methods including database search algorithms and tools for protein sequence analysis will be introduced. We will also discuss experimental strategies for MS protein quantification using stable isotope labeling techniques and fluorescent labeling. We will introduce several fungal proteomic studies to illustrate the use of these methods. This article will allow investigators to gain a working knowledge of proteomics along with some strengths and weaknesses associated with the techniques presented. PMID- 17344532 TI - Utero-tubal sperm transport and its impairment in endometriosis and adenomyosis. AB - The uterus is composed of different smooth muscle layers that serve various functions. First, menstrual debris is expulsed at the time of the menses. Second, sperm is transported in the preovulatory phase to maximize fertility, and third, the human embryo is placed in an adequate setting during implantation. Endometriosis is a gynecologic disorder leading to severe pain symptoms such as severe pain during menstruation (dysmenorrhea), chronic pelvic pain, pain during sexual intercourse (dyspareunia), and abnormal uterine bleeding. Besides, endometriosis is often associated with female infertility and exhibits a massive impairment in the physiology of uterine contractility that can be documented by the in vivo examination method of hysterosalpingoscintigraphy (HSSG). In addition, endometriosis is associated in 80-90% of subjects with adenomyosis and our data clearly indicate that sperm transport is disturbed by hyperperistalsis when at least one focus of adenomyosis can be detected via magnetic resonance imaging (MRI) and turns into dysperistalsis (a complete failure in sperm transport capacity) when diffuse adenomyosis affecting all myometrial uterine muscle layers is detected. Hence, dysperistalsis is significantly associated with reduced spontaneous pregnancy rates. We therefore recommend MRI and HSSG in every sterility workup. PMID- 17344533 TI - Should I stay or should I go? Transformation of time-discounted rewards in orbitofrontal cortex and associated brain circuits. AB - Animals prefer a small, immediate reward over a larger delayed reward (time discounting). Lesions of the orbitofrontal cortex (OFC) can either increase or decrease the breakpoint at which animals abandon the large delayed reward for the more immediate reward as the delay becomes longer. Here we argue that the varied effects of OFC lesions on delayed discounting reflect two different patterns of activity in OFC; one that bridges the gap between a response and an outcome and another that discounts delayed reward. These signals appear to reflect the spatial location of the reward and/or the action taken to obtain it, and are encoded independently from representations of absolute value. We suggest a dual role for output from OFC in both discounting delayed reward, while at the same time supporting new learning for them. PMID- 17344534 TI - Fluid dynamic models of flagellar and ciliary beating. AB - We have developed a fluid-mechanical model of a eucaryotic axoneme that couples the internal force generation of dynein molecular motors, the passive elastic mechanics of microtubules, and forces due to nexin links with a surrounding incompressible fluid. This model has been used to examine both ciliary beating and flagellar motility. In this article, we show preliminary simulation results for sperm motility in both viscous and viscoelastic fluids, as well as multiciliary interaction with a mucus layer. PMID- 17344535 TI - Azole therapy of clinical and experimental coccidioidomycosis. AB - The therapy of coccidioidomycosis has been an early target, both experimentally and clinically, for study of new members of the azole class of drugs, because of the recognition that coccidioidomycosis is one of the most difficult mycoses to treat, and because our research group and our collaborators have been eager to pioneer new therapies for this problem pathogen. There have been steady advances in the pharmacologic and antimicrobial properties of this class since the initial introduction of miconazole, and many patients with coccidioidomycosis have benefited. Perhaps the greatest contribution has been the development of well tolerated oral drugs that make possible prolonged courses of a conveniently administered agent, and perhaps the most impressive advance has been the utility of the agents in coccidioidal meningitis, at least as an adjunct to the polyenes. More potent agents are still required, so that complete biological cure can be attained in meningeal and nonmeningeal coccidioidomycosis. PMID- 17344536 TI - Mechanobiology of embryonic limb development. AB - Considerable evidence exists to support the hypothesis that mechanical forces have an essential role in healthy embryonic skeletal development. Clinical observations and experimental data indicate the importance of muscle contractions for limb development. However, the influence of these forces is seldom referred to in biological descriptions of bone development, and perhaps this is due to the fact that the hypothesis that mechanical forces are essential for normal embryonic skeletal development is difficult to test and elaborate experimentally in vivo, particularly in humans. Computational modeling has the potential to address this issue by simulating embryonic growth under a range of loading conditions but the potential of such models has yet to be fully exploited. In this article, we review the literature on mechanobiology of limb development in three main sections: (a) experimental alteration of the mechanical environment, (b) mechanical properties of embryonic tissues, and (c) the use of computational models. Then we analyze the main issues, and suggest how experimental and computational fields could work closer together to enhance our understanding of mechanobiology of the embryonic skeleton. PMID- 17344537 TI - The population biology of coccidioides: epidemiologic implications for disease outbreaks. AB - Studies of field- and patient-derived isolates conducted over the past 75 years have provided a general picture of the population structure of Coccidioides, the cause of coccidioidomycosis. Premolecular studies provided a general outline of the geographical range, epidemiology and distribution of the fungus. Recent studies based on molecular markers have demonstrated that the genus is comprised of two genetically diverse, and genetically isolated, species: Coccidioides immitis and C. posadasii. Both species are composed of biogeographically distinct populations. Structure for two of these populations (C. immitis from central California, and C. posadasii from southern Arizona) indicates that frequent genetic recombination occurs within the entire geographic range of each population, even though sex has never been observed in the genus. Outbreaks of coccidioidomycosis are not the result of the spread of a single clonal isolate, but are caused by a diversity of genotypes. Although it is now possible to match patient isolates to populations, the lack of apparent structure within each population and the current paucity of environmental isolates limit map-based epidemiological approaches to understanding outbreaks. Therefore, a comprehensive database comprised of soil-derived isolates from across the biogeographic range of Coccidioides will improve the utility of this approach. Appropriate collection of environmental isolates will assist the investigation of remaining questions regarding the population biology of Coccidioides. The comparative genomics of representative genotypes from both species and all populations of Coccidioides will provide a thorough set of genetic markers in order to resolve the population genetics of this pathogenic fungus. PMID- 17344538 TI - Molecular identification of coccidioides isolates from Mexican patients. AB - Molecular studies of the genome of the fungus Coccidioides have demonstrated two nearly identical, but well-identified species, Coccidioides immitis and C. posadasii, known as "California" and "non-California" species, respectively. The objective of this study was to determine, through molecular methods, whether both species of Coccidioides are present in Mexican patients with coccidioidomycosis and to estimate, their geographical distribution in Mexico. We analyzed 56 clinical isolates of Coccidioides spp. from Mexican patients. Molecular identification of each strain was done by means of real time PCR using TaqMan(R) probes to amplify single nucleotide polymorphisms (SNPs) in four target sequences, loci, named proline 157, proline 174, hexokinase 149 and glucose synthase 192. SNP analysis identified two of the 56 isolates as Coccidioides immitis and the remaining 54 as C. posadasii. The dual probe assay that included proline 157, proline 174 and glucose-synthase 192 gave consistent results on SNP differentiation between the two species. In contrast, the template matching hexokinase 149 gave negative results for any species in 34 samples. Our results did not show geographical overlap of the species, and they also confirmed that C. posadasii is the most frequent species in Mexico. A vast majority of C. posadasii strains were localized in the north-central region of the country. PMID- 17344539 TI - Modeling acardiac twin pregnancies. AB - Acardiac twin pregnancies are a rare but severe complication of monochorionic twinning, where the acardiac twin lacks cardiac function but nevertheless grows during pregnancy because it is perfused by the pump twin through a set of placental arterioarterial and venovenous anastomoses. Because the acardiac twin's body is only perfused by the pump twin's arterial blood, acardiac twins have reduced blood oxygen saturation (SO(2)) levels. Furthermore, the pump twin has reduced blood oxygen saturation because the anastomoses merge the blood of the two twins. We suggested that angiogenesis from hypoxia mediated neovascularization increases the capillary density in the acardiac twin and causes a continuously decreasing vascular resistance of the acardiac body. The pump twin therefore has a continuously increasing cardiac output and decreasing oxygen saturation, which may cause a vicious circle of increasing levels of pump twin complications, often leading to intrauterine fetal death. Our aim in this article was twofold. First, to summarize our previous modeling work of acardiac twin pregnancies, and add an estimate of the capillary density in mammals at different levels of SO(2) from a literature search on angiogenesis related to SO(2), Hypoxia Inducible Factor, and Vascular Endothelial Growth Factor. Second, to speculate that combination of these efforts and our most recent model of monochorionic twin pregnancies and twin-twin transfusion syndrome may result in an improved computational model for acardiac twin pregnancies, aimed at identifying early clinical prognostic markers for pump twin complications. PMID- 17344540 TI - Assessment of climate-coccidioidomycosis model: model sensitivity for assessing climatologic effects on the risk of acquiring coccidioidomycosis. AB - Understanding the predictive relationships between climate variability and coccidioidomycosis is of great importance for the development of an effective public health decision-support system. Preliminary regression-based climate modeling studies have shown that about 80% of the variance in seasonal coccidioidomycosis incidence for southern Arizona can be explained by precipitation and dust-related climate scenarios prior to and concurrent with outbreaks. In earlier studies, precipitation during the normally arid foresummer 1.5-2 years prior to the season of exposure was found to be the dominant predictor. Here, the sensitivity of the seasonal modeling approach is examined as it relates to data quality control (QC), data trends, and exposure adjustment methodologies. Sensitivity analysis is based on both the original period of record, 1992-2003, and updated coccidioidomycosis incidence and climate data extending the period of record through 2005. Results indicate that models using case-level data exposure adjustment do not suffer significantly if individual case report data are used "as is." Results also show that the overall increasing trend in incidence is beyond explanation through climate variability alone. However, results also confirm that climate accounts for much of the coccidioidomycosis incidence variability about the trend from 1992 to 2005. These strongly significant relationships between climate conditions and coccidioidomycosis incidence obtained through regression modeling further support the dual "grow and blow" hypothesis for climate-related coccidioidomycosis incidence risk. PMID- 17344541 TI - Reward prediction error computation in the pedunculopontine tegmental nucleus neurons. AB - In this article, we address the role of neuronal activity in the pathways of the brainstem-midbrain circuit in reward and the basis for believing that this circuit provides advantages over previous reinforcement learning theory. Several lines of evidence support the reward-based learning theory proposing that midbrain dopamine (DA) neurons send a teaching signal (the reward prediction error signal) to control synaptic plasticity of the projection area. However, the underlying mechanism of where and how the reward prediction error signal is computed still remains unclear. Since the pedunculopontine tegmental nucleus (PPTN) in the brainstem is one of the strongest excitatory input sources to DA neurons, we hypothesized that the PPTN may play an important role in activating DA neurons and reinforcement learning by relaying necessary signals for reward prediction error computation to DA neurons. To investigate the involvement of the PPTN neurons in computation of reward prediction error, we used a visually guided saccade task (VGST) during recording of neuronal activity in monkeys. Here, we predict that PPTN neurons may relay the excitatory component of tonic reward prediction and phasic primary reward signals, and derive a new computational theory of the reward prediction error in DA neurons. PMID- 17344542 TI - Learning about multiple attributes of reward in Pavlovian conditioning. AB - The nature of the reward representation in Pavlovian conditioning has been of perennial interest to students of associative learning theory. We consider the view that it consists of a range of different attributes, each of which may be governed by different learning rules. We investigated this issue through a series of experiments using a time-sensitive Pavlovian-to-instrumental transfer procedure, aiming to dissociate learning about temporal and specific sensory features of a reward. Our results successfully demonstrated that learning about these different features appears to be dissociable, with learning about the specific sensory features of a Pavlovian unconditioned stimulus (US) occurring very rapidly across a wide range of experimental procedures, while learning about the temporal features of the US occurred slightly less quickly and was more sensitive to parametric disruption. These results are discussed with regard to the potential independence or interdependence of the relevant learning processes, and to some recent neurophysiological recording and brain lesion work, which provide additional means to investigate these dissociations. PMID- 17344543 TI - Resisting the power of temptations: the right prefrontal cortex and self-control. AB - Imagine you are overweight and you spot your favorite pastry in the storefront of a bakery. How do you manage to resist this temptation? Or to give other examples, how do you manage to restrain yourself from overspending or succumbing to sexual temptations? The present article summarizes two recent studies stressing the fundamental importance of inhibition in the process of decision making. Based on the results of these studies, we dare to claim that the capacity to resist temptation depends on the activity level of the right prefrontal cortex (PFC). PMID- 17344544 TI - On the structure of phoneme categories in listeners with cochlear implants. AB - PURPOSE: To describe cochlear implant users' phoneme labeling, discrimination, and prototypes for a vowel and a sibilant contrast, and to assess the effects of 1 year's experience with prosthetic hearing. METHOD: Based on naturally produced clear examples of "boot," "beet," "said," and "shed" by 1 male and 1 female speaker, continua with 13 stimuli were synthesized for each contrast. Seven hearing controls labeled those stimuli and assigned them goodness ratings, as did 7 implant users at 1-month postimplant. One year later, these measures were repeated, and within category discrimination, d', was assessed. RESULTS: Compared with controls, implant users' vowel and sibilant labeling slopes were substantially shallower but improved over 1 year of prosthesis use. Their sensitivity to phonetic differences within phoneme categories was about half that of controls. The slopes of their goodness rating functions were shallower and did not improve. Their prototypes for the sibilant contrast (but not the vowels) were closer to one another and did not improve by moving apart. CONCLUSIONS: Implant users' phoneme labeling and within-category perceptual structure were anomalous at 1-month postimplant. After 1 year of prosthesis use, phoneme labeling categories had sharpened but within category discrimination was well below that of hearing controls. PMID- 17344545 TI - The objective and subjective evaluation of multichannel expansion in wide dynamic range compression hearing instruments. AB - PURPOSE: The effects of multichannel expansion on the objective and subjective evaluation of 20 listeners fitted binaurally with 4-channel, digital in-the-ear hearing instruments were investigated. METHOD: Objective evaluations were conducted in quiet using the Connected Speech Test (CST) and in noise using the Hearing in Noise Test (HINT) at 40, 50, and 60 dB SPL. Subjective evaluations were conducted by having each participant (a) rate their satisfaction regarding the amount of noise reduction they perceived daily and (b) indicate which expansion condition they preferred overall after a 2-week trial. Three expansion settings were programmed into the hearing aids: 4-channel expansion, expansion restricted to Channels 1 and 2 only, and expansion off. RESULTS: Listeners performed significantly better in quiet (CST) and in noise (HINT) for the off condition than for either multichannel condition; however, restricting expansion to Channels 1 and 2 improved objective performance in quiet and in noise relative to the 4-channel condition. Conversely, satisfaction ratings were significantly greater for both multichannel conditions than for the off condition; however, satisfaction ratings were similar for the restricted and the 4-channel conditions. Overall, listeners preferred any form of multichannel expansion to no expansion; however, overall preference was similar for the restricted and the 4 channel conditions. CONCLUSIONS: Hearing instrument users prefer the use of multichannel expansion despite the fact multichannel expansion may significantly reduce the recognition of low-level speech in quiet and in noise. Although restricting expansion to Channels 1 and 2 (i.e., 2000 Hz and below) maintained subjective benefit for wide dynamic range compression hearing instrument users, the recognition of low-level speech was not completely preserved. PMID- 17344546 TI - Effects of training on speech recognition performance in noise using lexically hard words. AB - PURPOSE: This study examined how repeated presentations of lexically difficult words within a background noise affect a listener's ability to understand both trained (lexically difficult) and untrained (lexically easy) words in isolation and within sentences. METHOD: In the 1st experiment, 9 young listeners with normal hearing completed a short-term auditory training protocol (5 hr) while 8 other young listeners with normal hearing completed a similar protocol lasting about 15 hr in the 2nd experiment. All training made use of multiple talkers and was in a closed-set condition. Feedback was provided on a trial-to-trial basis and consisted of either orthographic or orthographic and auditory feedback. Performance on both the trained and untrained words in isolation and within sentences was measured pre- and posttraining. RESULTS: Listeners' performance improved significantly for the trained words in an open and closed-set condition, as well as the untrained words in the closed-set condition. Although there was no mean improvement in the number of keywords identified within sentences posttraining, 50% of the listeners who completed the long-term training showed improvement beyond the 95% critical difference. CONCLUSIONS: With enough training on isolated words, individual listeners can generalize knowledge gained through isolated word training to the recognition of lexically similar words in running speech. PMID- 17344548 TI - Children's weighting strategies for word-final stop voicing are not explained by auditory sensitivities. AB - PURPOSE: It has been reported that children and adults weight differently the various acoustic properties of the speech signal that support phonetic decisions. This finding is generally attributed to the fact that the amount of weight assigned to various acoustic properties by adults varies across languages, and that children have not yet discovered the mature weighting strategies of their own native languages. But an alternative explanation exists: Perhaps children's auditory sensitivities for some acoustic properties of speech are poorer than those of adults, and children cannot categorize stimuli based on properties to which they are not keenly sensitive. The purpose of the current study was to test that hypothesis. METHOD: Edited-natural, synthetic-formant, and sine wave stimuli were all used, and all were modeled after words with voiced and voiceless final stops. Adults and children (5 and 7 years of age) listened to pairs of stimuli in 5 conditions: 2 involving a temporal property (1 with speech and 1 with nonspeech stimuli) and 3 involving a spectral property (1 with speech and 2 with nonspeech stimuli). An AX discrimination task was used in which a standard stimulus (A) was compared with all other stimuli (X) equal numbers of times (method of constant stimuli). RESULTS: Adults and children had similar difference thresholds (i.e., 50% point on the discrimination function) for 2 of the 3 sets of nonspeech stimuli (1 temporal and 1 spectral), but children's thresholds were greater for both sets of speech stimuli. CONCLUSION: Results are interpreted as evidence that children's auditory sensitivities are adequate to support weighting strategies similar to those of adults, and so observed differences between children and adults in speech perception cannot be explained by differences in auditory perception. Furthermore, it is concluded that listeners bring expectations to the listening task about the nature of the signals they are hearing based on their experiences with those signals. PMID- 17344547 TI - Children with specific language impairments perceive speech most categorically when tokens are natural and meaningful. AB - PURPOSE: To examine perceptual deficits as a potential underlying cause of specific language impairments (SLI). METHOD: Twenty-one children with SLI (8;7 11;11 [years;months]) and 21 age-matched controls participated in categorical perception tasks using four series of syllables for which perceived syllable initial voicing varied. Series were either words or abstract nonword syllables and either synthesized or high-quality edited natural utterances. Children identified and discriminated (a) digitally edited tokens of naturally spoken "bowl"-"pole", (b) synthesized renditions of "bowl"-"pole", (c) natural "ba" "pa", and (d) synthetic "ba"-"pa". RESULTS: Identification crossover locations were the same for both groups of children, but there was modestly less accuracy on unambiguous endpoints for children with SLI. Planned comparisons revealed these effects to be limited to synthesized speech. Children with SLI showed overall reduced discrimination, but these effects were limited to abstract nonword syllables. CONCLUSION: Overall, children with SLI perceived naturally spoken real words comparably to age-matched peers but showed impaired identification and discrimination of synthetic speech and of abstract syllables. Poor performance on speech perception tasks may result from task demands and stimulus properties, not perceptual deficits. PMID- 17344549 TI - The relationship between nonverbal cognitive functions and hearing loss. AB - PURPOSE: This study investigated the relationship between hearing loss and memory and attention when nonverbal, visually presented cognitive tests are used. METHOD: Hearing loss (pure-tone audiometry) and IQ were measured in 30 participants with mild to severe hearing loss. Participants performed cognitive tests of pattern recognition memory, sustained visual attention, and spatial working memory. All cognitive tests were selected from the Cambridge Neuropsychological Test Automated Battery (CANTAB expedio; Cambridge Cognition Ltd., 2002). Regression analyses were performed to examine the relationship between hearing loss and these cognitive measures of memory and attention when controlling for age and IQ. RESULTS: The data indicate that hearing loss was not associated with decreased performance on the memory and attention tests. In contrast, participants with more severe hearing loss made more use of an efficient strategy during performance on the spatial working memory subtest. This result might reflect the more extensive use of working memory in daily life to compensate for the loss of speech information. CONCLUSIONS: The authors conclude that the use of nonverbal tests is essential when testing cognitive functions of individuals with hearing loss. PMID- 17344550 TI - Effects of elicitation task variables on speech production by children with cochlear implants. AB - Given the interest in comparing speech production development in children with normal hearing and hearing impairment, it is important to evaluate how variables within speech elicitation tasks can differentially affect the acoustics of speech production for these groups. In a first experiment, children (6-14 years old) with cochlear implants produced a set of monosyllabic words either in isolation or while simultaneously signing the word. Acoustical analyses indicated no change in word duration, voice onset time, intensity, or fundamental frequency between isolated and simultaneous signing conditions. In a second experiment, the same children verbally repeated words that were signed by a video model. The model either signed with inflection or without. Words repeated after inflected models were higher in fundamental frequency and intensity and were more intelligible. In addition, children with poorer speech perception skills sometimes produced the monosyllables as 2 syllables, but this only occurred for words that had multiple sign movements. The results have implications for the comparison of speech development between children with normal hearing and those with hearing impairment. PMID- 17344551 TI - F2 locus equations: phonetic descriptors of coarticulation in 17- to 22-month-old children. AB - The general purpose of this research was to describe coarticulation across voiced stop consonant place of articulation in 10 children younger than 2 years of age. A total of 1,182 voiced stop CV productions was analyzed using the locus equation metric, which yielded 3 regression lines that described the relation of F2 onset and F2 vowel for /bV/, /dV/, and /gV/ productions. The results revealed significant differential effects for slope and y-intercept as a function of stop consonant place of articulation. The ordering of the mean slope values for stop consonant place of articulation was /g/>/b/ and /d/, indicating that /g/ was produced with significantly greater coarticulation than /b/ or /d/. However, the unique vowel allophonic pattern of [g] coarticulation reported in the literature for English-speaking adults was generally not learned by these young children. Group and individual coarticulation trends are described in relation to developmental theories of sound acquisition. Results suggest that early coarticulation patterns are phoneme specific. PMID- 17344552 TI - Chest wall motion during speech production in patients with advanced ankylosing spondylitis. AB - PURPOSE: To test the hypothesis that ankylosing spondylitis (AS) alters the pattern of chest wall motion during speech production. METHOD: The pattern of chest wall motion during speech was measured with respiratory inductive plethysmography in 6 participants with advanced AS (5 men, 1 woman, age 45+/-8 years, Schober test 1.45+/-1.5 cm, Bath Ankylosing Spondylitis Functional Index [BASFI] score 6+/-1.7) and 6 healthy volunteers, matched for age and gender. Measurements were made with participants in the upright seated and upright standing body position. RESULTS: During reading in the seated and standing body positions, the rib cage wall volume displacements were smaller and abdominal wall volume displacements were larger in participants with AS than in healthy controls. There were no differences in the overall lung volume displacements recorded during the expiratory limb of reading in either body position. In the participants with AS, the rib cage remained near the end-expiratory level in both the seated and standing body position, differing from that for the control group. CONCLUSION: In individuals with advanced AS, the abdomen is the primary contributor to volume displacement. In the absence of speech impairment in participants with AS, the data show the capacity of the abdomen to compensate for the decreased compliance of the rib cage. PMID- 17344553 TI - Articulator movement associated with the development of prosodic control in children. AB - This study explored the relationship between articulator movement and prosody in children at different developmental ages. Jaw, lower lip, and upper lip kinematics were examined in 4-, 7-, and 11-year-old children as they produced the declarative and interrogative forms of utterances "Show Bob a bot" and "Show Pop a pot." Articulator movement differences were found between declaratives and interrogatives during the production of vowel and consonant targets. The 7- and 11-year-olds differentiated the duration and displacement of their articulator movements to distinguish between declaratives and interrogatives. Several age related differences in movement duration between the 4-year-olds and the older participants were associated with the production of these targets. Productions of declaratives and interrogatives were not associated with any significant differences in articulator movement variability, although variability did decrease significantly with maturation. The results suggest that children modify their articulator movements to meet the prosodic and linguistic demands of the task. While 4-year-olds appear to be able to modify lip and jaw movement to mark the declarative-interrogative contrast, refinement of these movements continues throughout childhood. PMID- 17344554 TI - Internal versus external: oral-motor performance as a function of attentional focus. AB - PURPOSE: Previous studies (e.g., G. Wulf, M. Hoss, & W. Prinz, 1998; G. Wulf, B. Lauterbach, & T. Toole, 1999; for a review, see G. Wulf & W. Prinz, 2001) have reported that limb motor performance is enhanced when individuals adopt an external focus (focusing on the effect of the movement) versus an internal focus of attention (focusing on body parts such as the muscles of the hand). This study tested the hypothesis that the effects of attentional focus on limb performance would also occur in the oral-facial system. METHOD: Two groups of 23 participants were administered both hand and tongue impulse force control tasks in which each group was randomly assigned either an internal or an external focus of attention. Participants were required to exert rapid pressure bursts to achieve a target force level of 20% of their maximal strength. RESULTS: Consistent with limb studies, findings revealed a significant advantage of an external focus (greater accuracy, less variability) for both the hand and tongue control tasks, as opposed to an internal focus of attention. CONCLUSIONS: Results are discussed relative to a constrained-action theory of motor control and future application to speech motor learning. PMID- 17344555 TI - The effect of temporal adverbials on past tense production by children with specific language impairment. AB - PURPOSE: Children with specific language impairment (SLI) often fail to produce past tense forms in obligatory contexts, although the factors affecting such inconsistency are not well understood. This study examined the influence of accompanying temporal adverbials (e.g., just, already) on the past tense production of these children. METHOD: Fifteen preschool-aged children with SLI, 15 typically developing children matched for age (TD-A) and 15 younger typically developing children matched for mean length of utterance (TD-MLU) participated in the study. The children responded to probes that obligated the use of past tense forms. The verbal context provided by the experimenter for half of the items included a temporal adverbial. RESULTS: Overall, the SLI and TD-MLU groups produced past tense less frequently than the children in the TD-A group, and there were no significant differences between the SLI and the TD-MLU groups. However, both the SLI and the TD-MLU participants produced past tense forms less frequently when temporal adverbials were included than when they were absent. CONCLUSIONS: These findings suggest that the tendency to use past tense by the children with SLI and their younger MLU-matched peers may not have been independent of other types of temporal information. PMID- 17344556 TI - Predictors of expressive vocabulary growth in children with autism. AB - PURPOSE: The purpose of this exploratory study was to examine the variability and predictors of expressive vocabulary development in children with autism and very delayed language. METHOD: This study involved 35 children with autism whose initial chronological ages were between 20 and 71 months and whose initial expressive vocabularies were less than 60 words. Their expressive vocabularies were measured at baseline and at 6, 12, and 24 months following the start of intervention using the MacArthur-Bates Communicative Developmental Inventory (L. Fenson et al., 1993). RESULTS: A cluster analysis revealed 4 distinct patterns of expressive vocabulary development over 2 years. The number of words said, the presence of verbal imitation skills and pretend play skills with objects, and the number of gestures to initiate joint attention at baseline were all associated with the cluster of children who demonstrated the most rapid expressive vocabulary growth over time. The 2 clusters of children who demonstrated the least vocabulary growth had the most significant developmental delays and autism severity at 6 months, but not at baseline. CONCLUSIONS: This study confirms the heterogeneity in language development in young children with autism and, consistent with other reports, confirms that specific prelinguistic skills are predictive of development. PMID- 17344557 TI - Conceptual organization at 6 and 8 years of age: evidence from the semantic priming of object decisions. AB - PURPOSE: The purpose of this study was to examine children's knowledge of semantic relations. METHOD: In Experiment 1, the 6-year-olds, 8-year-olds, and adults participated in an object decision task. Participants in the primed group made object decisions in response to primes that were related taxonomically, thematically, or perceptually to the target objects. Those in the unprimed group made decisions about the same stimuli without the benefit of primes. In Experiment 2, the children in the primed group explained the taxonomic and thematic relations between the prime-target pairs used in Experiment 1. RESULTS: In Experiment 1, the strength of semantic relations did not vary with type or age, as taxonomic priming was as strong as thematic priming and the degree of priming did not reliably differentiate the 3 age groups. Differential priming effects between taxonomic and perceptual conditions, the former hastening and the latter slowing responses, suggested that the relation binding object concepts into taxonomies was not reducible to common physical features. In Experiment 2, the 6-year-olds had more difficulty describing taxonomic than thematic relations, whereas the 8-year-olds described both with ease. CONCLUSIONS: Contrary to the shift hypothesis, taxonomic and thematic relationsstructure concepts in children as young as 6 and into adulthood. In accord with the performance hypothesis, 6 year-olds' representations of taxonomic relations are fragile and vulnerable to high task demands. PMID- 17344558 TI - Differences in the nonword repetition performance of children with and without specific language impairment: a meta-analysis. AB - PURPOSE: This study presents a meta-analysis of the difference in nonword repetition performance between children with and without specific language impairment (SLI). The authors investigated variability in the effect sizes (i.e., the magnitude of the difference between children with and without SLI) across studies and its relation to several factors: type of nonword repetition task, age of SLI sample, and nonword length. METHOD: The authors searched computerized databases and reference sections and requested unpublished data to find reports of nonword repetition tasks comparing children with and without SLI. RESULTS: Children with SLI exhibited very large impairments in nonword repetition, performing an average (across 23 studies) of 1.27 standard deviations below children without SLI. A moderator analysis revealed that different versions of the nonword repetition task yielded significantly different effect sizes, indicating that the measures are not interchangeable. The second moderator analysis found no association between effect size and the age of children with SLI. Finally, an exploratory meta-analysis found that children with SLI displayed difficulty repeating even short nonwords, with greater difficulty for long nonwords. CONCLUSIONS: These findings have potential to affect how nonword repetition tasks are used and interpreted, and suggest several directions for future research. PMID- 17344559 TI - The role of selected lexical factors on confrontation naming accuracy, speed, and fluency in adults who do and do not stutter. AB - PURPOSE: The purpose of this study was to investigate whether lexical access in adults who stutter (AWS) differs from that in people who do not stutter. Specifically, the authors examined the role of 3 lexical factors on naming speed, accuracy, and fluency: word frequency, neighborhood density, and neighborhood frequency. If stuttering results from an impairment in lexical access, these factors were hypothesized to differentially affect AWS performance on a confrontation naming task. METHOD: Twenty-five AWS and 25 normally fluent comparison speakers, matched for age and education, participated in a confrontation naming task designed to explore within-speaker performance on naming accuracy, speed, and fluency based on stimulus word frequency and neighborhood characteristics. Accuracy, fluency, and reaction time (from acoustic waveform analysis) were computed. RESULTS: In general, AWS demonstrated the same effects of lexical factors on their naming as did adults who do not stutter. However, accuracy of naming was reduced for AWS. Stuttering rate was influenced by word frequency but not other factors. CONCLUSIONS: Results suggest that AWS could have a fundamental deficit in lexical retrieval, but this deficit is unlikely to be at the level of the word's abstract phonological representation. Implications for further research are discussed. PMID- 17344560 TI - The language use inventory for young children: a parent-report measure of pragmatic language development for 18- to 47-month-old children. AB - PURPOSE: To demonstrate the internal reliability and discriminative validity of the Language Use Inventory for Young Children (LUI; D. K. O'Neill, 2002), a newly developed parent-report measure designed to assess pragmatic language development in 18-47-month-olds. METHOD: To examine internal reliability, the LUI was completed by mail by 177 parents recruited from the University of Waterloo's Centre for Child Studies database, 175 of whom completed the LUI again within 4 weeks to assess test-retest reliability. To examine discriminative validity, 49 parents of children awaiting assessment at a local speech-language clinic and 49 parents of typically developing children recruited from the Centre for Child Studies database and matched in age and sex to the clinic group completed the LUI. RESULTS: Alpha values for the subscales of the LUI were at or above acceptable levels (.80-.98), and steady growth in children's pragmatic language development was demonstrated. The study of discriminant validity revealed sensitivity and specificity levels over 95%. CONCLUSIONS: The LUI's internal reliability and stability were strongly supported and its sensitivity and specificity in distinguishing between typically developing and language-delayed children exceeded even the most stringent criteria of 90% accuracy. PMID- 17344562 TI - Organ transplantation and the Human Tissue Act. PMID- 17344561 TI - Phonological neighborhood and word frequency effects in the stuttered disfluencies of children who stutter. AB - PURPOSE: The purpose of this study was to examine (a) the role of neighborhood density (number of words that are phonologically similar to a target word) and frequency variables on the stuttering-like disfluencies of preschool children who stutter, and (b) whether these variables have an effect on the type of stuttering like disfluency produced. METHOD: A 500+ word speech sample was obtained from each participant (N = 15). Each stuttered word was randomly paired with the firstly produced word that closely matched it in grammatical class, familiarity, and number of syllables/phonemes. Frequency, neighborhood density, and neighborhood frequency values were obtained for the stuttered and fluent words from an online database. RESULTS: Findings revealed that stuttered words were lower in frequency and neighborhood frequency than fluent words. Words containing part-word repetitions and sound prolongations were also lower in frequency and/or neighborhood frequency than fluent words, but these frequency variables did not have an effect on single-syllable word repetitions. Neighborhood density failed to influence the susceptibility of words to stuttering, as well as the type of stuttering-like disfluency produced. CONCLUSIONS: In general, findings suggest that neighborhood and frequency variables not only influence the fluency with which words are produced in speech, but also have an impact on the type of stuttering-like disfluency produced. PMID- 17344563 TI - Teaching in the healthcare setting. PMID- 17344564 TI - Developing your teaching style: increasing effectiveness in healthcare teaching. AB - This paper reports the first stage in the development of a tool, the Six Staffordshire Teaching Styles Questionnaire, designed to raise awareness in teachers about their teaching style. Effective teachers are adaptable and flexible in providing variety in their teaching activities, aiming to match their manipulation of the teaching and learning environment to the needs of the learner, but teachers should also know what type of activities they are most effective at delivering. Just as mismatched learning styles can cause dysfunctional learning situations, one of the causes of stress in teachers can be an incongruency between the type of activities they believe are effective, or feel they are good at carrying out, and external expectations of "good teaching". PMID- 17344565 TI - Heights and haematology: the story of haemoglobin at altitude. AB - In order to compensate for the low partial pressure of oxygen at altitude, the human body undergoes a number of physiological changes. A vital component in this process is the increase in the concentration of circulating haemoglobin. The role of HIF-1alpha, erythropoietin and red blood cells in this acclimatisation process is described, together with the fall in plasma volume that increases the concentration of haemoglobin in the early stages of hypoxic exposure. PMID- 17344566 TI - Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism. AB - A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients. PMID- 17344567 TI - A second corneal arcus? PMID- 17344568 TI - Coronary artery bypass surgery in elderly people. AB - An increasing number of elderly individuals are now undergoing coronary artery bypass surgery. Elderly patients, compared with patients of a younger age group, present for surgery with a greater burden of risk factors and reduced functional levels. Short-term outcomes are hence poorer in them. But symptom relief occurs in most survivors and is accompanied by excellent rates of long-term survival and a good quality of life. Therefore, an individualised risk-benefit profile must be carefully constructed by clinicians, taking into account several different factors and not just age alone. This review summarises the current concepts of coronary artery bypass surgery from the perspective of the very old. PMID- 17344569 TI - How do you treat bleeding disorders with desmopressin? AB - Desmopressin is an analog of vasopressin that exerts a substantial haemostatic effect by inducing the release of von Willebrand factor from its storage sites in endothelial cells. It has proved useful in treating or preventing bleeding episodes in patients with von Willebrand disease, haemophilia A and platelet function defects. Its efficacy in achieving a satisfactory level of haemostasis has reduced the use of blood products to treat bleeding episodes. Clinicians need to become familiar with the use of this drug that has become a home medication for many patients with inherited bleeding disorders. PMID- 17344570 TI - Paradoxical vocal cord motion disorder: past, present and future. AB - Paradoxical vocal cord motion disorder (PVCM), also called vocal cord dysfunction, is an important differential diagnosis for asthma. The disorder is often misdiagnosed as asthma leading to unnecessary drug use, very high medical utilisation and occasionally tracheal intubation or tracheostomy. Laryngoscopy is the gold standard for diagnosis of PVCM. Speech therapy and psychotherapy are considered the cornerstone of management of this disorder. The aim of this article is to increase the awareness of PVCM among doctors, highlighting the main characteristics that distinguish it from asthma and discuss the recent medical achievements and the possible future perspectives related to this disorder. PMID- 17344571 TI - Patent foramen ovale and atrial septal aneurysm in cryptogenic stroke. AB - Up to 40% of acute ischaemic strokes in young adults are cryptogenic in nature, that is, no cause is determined. In more than half of these patients, patent foramen ovale (PFO) is seen along with an increased incidence of atrial septal aneurysm. The commonest method of investigation is echocardiography (preferably transoesophageal echocardiography). On the basis of available evidence, low risk patients are treated with antiplatelet agents and high risk patients with warfarin. There are inconclusive data on the efficacy of PFO closure to prevent stroke recurrence. However, if there is recurrent stroke or intolerance to medical therapy, percutaneous closure is carried out. PMID- 17344572 TI - Inhaled insulins. AB - As a result of knowledge gained from the management of asthma with inhalers and nebulisers, pulmonary delivery devices for insulin have been developed. Particle size of the aerosol particularly influences drug delivery. Although several pharmaceutical companies are developing different systems, Pfizer have launched the first inhaled insulin (Exubera). Clinical trials have taken place in patients with both type 1 and type 2 diabetes, but have shown similar glucose control as subcutaneous insulin delivery. However, patient satisfaction does seem to be increased in patients taking inhaled insulins. Further studies are needed to investigate compliance, side-effect profiles, quality of life, long-term glycaemia control and cost effectiveness. PMID- 17344573 TI - Increased prevalence of gastrointestinal symptoms in patients with allergic disease. AB - BACKGROUND: Children with allergic diseases such as asthma and atopic dermatitis experience increased gastrointestinal symptoms. Further, physiological and histological abnormalities of the gastrointestinal tract in patients with allergic diseases have been reported. It is not certain whether adult patients experience increased gastrointestinal symptoms. METHODS: A retrospective, case control study of 7235 adult (> or =20 years old) primary care patients was conducted. A general practitioner diagnosis of irritable bowel syndrome was used to serve as a marker of lower gastrointestinal symptoms. The prevalence of lower gastrointestinal symptoms was calculated in patients with asthma or allergic rhinitis and compared with that in patients with other chronic diseases (insulin dependent diabetes mellitus, osteoarthritis and rheumatoid arthritis) and with the remaining population. RESULTS: Gastrointestinal symptoms were significantly more common in patients with asthma (9.9%) as compared with patients with chronic diseases (4.9%; odds ratio (OR) 2.13, 95% confidence interval (CI) 1.39 to 2.56; p<0.002) or the remaining non-asthmatic population (5.5%; OR 1.89, 95% CI 1.39 to 2.56; p<0.001). Gastrointestinal symptoms were also significantly more common in patients with allergic rhinitis (7.9%) as compared with patients with chronic diseases (4.9%; OR 1.66, 95% CI 1.02 to 2.7; p<0.05) and the remaining population (5.5%; OR 1.47, 95% CI 1.04 to 2.1; p<0.02). This phenomenon was independent of age, sex and inhaled asthma therapy in the case of patients with asthma. CONCLUSIONS: Our findings support the hypothesis that lower gastrointestinal symptoms are more common in patients with allergic diseases such as asthma and allergic rhinitis. PMID- 17344574 TI - Early percutaneous transhepatic gallbladder drainage compared with endoscopic retrograde cholangiopancreatography and papillotomy treatment for severe gallstone associated acute pancreatitis. AB - OBJECTIVE: Percutaneous transhepatic gallbladder drainage (PTGD) was compared with endoscopic treatment (within 72 hours after the onset of symptoms) in patients with severe biliary pancreatitis to evaluate the curative effect of PTGD in preventing bile track complications in these patients. METHODS: Eligible patients were randomised to receive early treatment with PTGD or endoscopic treatment. If the initial emergency endoscopic or PTGD treatment failed, patients received another drainage treatment within 24 hours. From November 2001 to August 2005, 101 patients were randomly assigned to early PTGD (n = 51) or endoscopic retrograde cholangiopancreatography (ERCP) (n = 50). Overall mortality, mortality due to pancreatitis and complications were compared in these two groups. RESULTS: 48 of 52 patients were successfully treated with ERCP and 53 of 55 with PTGD. Seven patients (6.9%; three in the endoscopic treatment group and four in the PTGD group) died within four months after the onset of pancreatitis (p = 0.798); three patients in the endoscopic group and three in the PTGD group died from acute biliary pancreatitis. The overall rate of complications was similar in the two groups and there were no major differences in the incidence of local or systemic complications. CONCLUSIONS: PTGD treatment is a simple, convenient and effective treatment of severe gallstone associated acute pancreatitis when endoscopic treatment fails. PMID- 17344576 TI - Clinical attachments: fond farewell or new beginning? A survey of the attitudes and practice of medical consultants and international medical graduates. AB - OBJECTIVES: To analyse the experience of clinical attachment (CA) of international medical graduates (IMGs) and consultants. DESIGN: Analysis of questionnaires and CVs. SETTING AND PARTICIPANTS: 573 IMGs applying for a house officer post and 102 consultant physicians working in North East England. RESULTS: IMGs had spent a mean of 16 months unemployed, of which 3.8 months was spent on CAs. The median number of CAs was two and the average number of applications sent before obtaining a CA was 73. 90% of IMGs found their CA helpful and 57% would not take up a post without a CA first. Criticisms related to lack of responsibility, isolation and poor job prospects. 90% would apply for honorary posts if advertised. 73% had received induction at the onset of placement, but only 32% had been assessed at the end. 50% of consultants took CAs and only 4% were thinking of stopping doing so. Those without CAs blamed work pressure (43%) and pressure from their employer (23%). CONCLUSIONS: There are deficiencies in pastoral care, the application process and assessment, but CAs are valued by IMGs and offered by half the consultants surveyed. New immigration rules will mean fewer IMGs will come to the UK, but CAs will be needed by those that do, as well by refugees and European Economic Area (EEA) graduates. The tradition of CAs for international graduates could be used to accommodate those coming to the UK on exchanges and scholarships and form part of the recently announced Medical Training Initiative for IMGs. PMID- 17344575 TI - Prevalence and risk factors of fatty liver disease in the Shuiguohu district of Wuhan city, central China. AB - BACKGROUND: Fatty liver disease (FLD) is highly prevalent in Western countries, but recent data have shown that FLD is also emerging in China. AIM: To investigate the prevalence and risk factors of FLD in the Shuiguohu district of Wuhan city, central China, during 1995-2004. METHODS: 12247 individuals (7179 men and 5068 women) over 18 years of age who were living in the area were investigated for FLD in the Zhongnan Hospital of Wuhan University from 1995 to 2004. FLD was determined by the ultrasonographic method. Height, weight, blood pressure, fasting blood sugar, alanine aminotransferase, total cholesterol and triglyceride were determined by routine laboratory methods. RESULTS: The prevalence of FLD was 12.5% in 1995, and rose gradually to 24.5% by 2003-4. The prevalence was twice as high in men (28.1%) as in women (13.8%), and increased with age in females, and males <60 years of age. Multivariate analysis showed that several risk factors were profoundly associated with the prevalence of FLD, including male sex, old age, obesity, hyperlipidaemia (cholesterol or triglyceride), fasting hyperglycemia and hypertension. CONCLUSION: The prevalence of FLD in the Shuiguohu district of Wuhan city, central China, was shown to have increased during the 10-year period, 1995 to 2004. The FLD was found to be closely associated with sex, age, obesity and other metabolic syndrome features. PMID- 17344577 TI - Raised cardiac troponin T levels in patients without acute coronary syndrome. AB - OBJECTIVE: To investigate the frequency, diagnosis and outcome of patients admitted to hospital with acute coronary syndrome (ACS) or other conditions associated with raised levels of cardiac troponin T. DESIGN: Observational study. SETTING: A large university hospital. PATIENTS: Consecutive patients admitted over an 8-week period who had a serum troponin T test as part of their clinical assessment were included. Patients were separated into those with raised (> or =0.01 microg/l) or normal (<0.01 microg/l) troponin T levels, and further categorised into those with or without a diagnosis of ACS. MAIN OUTCOME MEASURES: In-hospital mortality in all patients; and 6-month hospital re-admissions and all cause mortality in patients without or with ACS and raised levels of troponin T. RESULTS: Of 1021 patients, 118 patients had no ACS but raised troponin T levels, 195 had ACS with raised troponin T, 80 had ACS with normal troponin T and 628 had no ACS with normal troponin T. Their in-hospital all-cause mortalities were 36%, 18%, 0% and 3%, respectively (p<0.001, highest mortality v other groups). 6-month all-cause mortality remained higher in patients without ACS and with raised levels of troponin T than in those with ACS and raised troponin T (42% v 29%; p = 0.020). CONCLUSIONS: Patients without ACS but with raised levels of troponin T comprised 38% of all hospitalised patients found to have raised troponin T. These patients had worse in-hospital and 6-month outcome than those having ACS with raised levels of troponin T. PMID- 17344578 TI - NT-proBNP and the diagnosis of left ventricular systolic dysfunction within two acute NHS trust catchment areas: the initial Teesside experience. AB - PURPOSE: To evaluate the predictive value of N-terminal pro B-type natiuretic peptide (NT-proBNP) reference cut-off values as diagnostic markers for left ventricular systolic dysfunction (LVSD). STUDY DESIGN: A retrospective study assessing the use of NT-proBNP in the diagnostic algorithm for the investigation of patients with suspected signs and symptoms of LVSD presenting to primary care. RESULTS: A generic NT-proBNP cut-off (150 ng/l) value has similar negative and positive predictive valves, specificity and sensitivity compared to age and sex specific cut-off values. CONCLUSION: When using NT-proBNP as a triage tool for screening patients with signs and symptoms suggestive of LVSD, a simple generic cut-off level is as effective as more complex age sex specific cut-off values. PMID- 17344579 TI - Diagnostic greed: using pictures to highlight diagnostic errors. PMID- 17344580 TI - p38 mitogen-activated protein kinase plays a critical role in the control of energy metabolism and development of cardiovascular diseases. AB - p38 mitogen-activated protein kinase (p38) is a member of MAP kinase family. Its wide-spectrum roles in the control of energy metabolism have been indicated in numerous studies. p38 participates in the energy metabolism in all major tissues/organs involved in the control of energy metabolism, including adipose tissue, skeletal muscles, islet cells, and liver. In white adipose tissue, p38 plays an important role in adipose differentiation and glucose uptake although it is still inconclusive whether this role of p38 is stimulatory or inhibitory. The stimulatory role of p38 in transcription of the uncoupling protein 1 (UCP1) gene in brown adipose tissue is relatively clear. A fundamental role for p38 in the differentiation of skeletal muscles and mitochondrial biogenesis in skeletal muscles is rather definitive although the role of p38 in glucose uptake of skeletal muscles remains controversial. In islet cells, p38 appears to be involved in beta-cell apoptosis. p38 has been indicated in the control of preproinsulin gene transcription, but remains controversial. However, it seems clear that p38 does not play a significant role in insulin secretion. In the liver, p38 plays a central role in hepatic glucose and lipid metabolism. Activation of p38 participates in the processes to increase blood glucose levels through reducing glycogen synthesis and increasing hepatic gluconeogenesis. p38 appears to prevent fat storage by inhibiting hepatic lipogenesis and promoting fatty acid oxidation in the liver. Additionally, p38 may play a critical role in cholesterol metabolism by regulating expression of the LDLR gene and bile metabolism. p38 does not only participate in various physiological and pathophysiological processes in cardiomyocytes, but also is heavily involved in the development of atherosclerotic lessions through its influences on monocytes/macrophages, vascular endothelial cells, and vascular smooth muscle cells. PMID- 17344581 TI - [Research progress of H5N1 influenza viruses and the threat to human]. AB - Human, birds and other mammals can be infected by avian influenza A (H5N1) virus. Bird infections spread among continents in the last 2 years. Human infections become endemic in certain areas, characterized with young patients and high mortality. An unprecedented epizootic avian influenza A (H5N1) virus that is highly pathogenic has crossed the species barrier in Asia to cause many human fatalities and poses an increasing pandemic threat. This summary describes the features of human infection with influenza A (H5N1) in epidemiology and etiology and reviews recommendations for prevention. PMID- 17344582 TI - Prospects of using organs and cells from pigs for transplantation into humans. AB - Once pig organs can be transplanted into humans, transplantation will move into a new era. There will be unlimited access to undamaged organs, and cells for transplantation and, eventually, donation from deceased or live human beings will become obsolete. Furthermore, it will be possible to alleviate graft rejection, at least in part, by genetic modification of the source animal. Currently, there are three major obstacles to performing transplantations from pig to man: a powerful immune barrier, a potential risk of transmitting microorganisms, particularly endogenous retrovirus, and ethical issues related to the future recipients and to society at large. This article will first discuss the ongoing work with regards to overcoming the current obstacles. Also, the many potential advantages of using pig organs will be discussed in some detail. Furthermore, lessons learned from attempts at transplanting porcine cells to patients will be reviewed. PMID- 17344583 TI - Association between islet xenograft rejection mediated by activated macrophages and upregulated chemokines. AB - OBJECTIVE: Our previous study has shown that porcine antigen-primed and CD4+ T cells activated macrophages are capable of the Recognition and rejection of porcine xenografts but not mouse allografts, and therefore suggested the involvement of signaling between the graft and macrophages in this specific graft recognition and destruction. METHODS: NOD-SCID mice were transplanted with fetal pig pancreatic fragment (FPP) before adoptive transfer with exogenous macrophages isolated from rejecting FPP xenografts of BALB/c recipient mice. The exogenous macrophages were tracked by Ly5.1 surface antigen or via CSFE staining. Gene expression of CCR2 and CCR5 and their chemokines in transplanted FPP xenografts was evaluated by real-time PCR. RESULTS: After the adoptive transfer, recently transplanted but not established FPP xenografts were rejected by exogenous activated macrophages. In the meantime, greater level of chemokine gene expression was detected in recently-transplanted compared with the established xenografts. Furthermore, expression of both CCR2 and CCR5 genes was enhanced significantly in activated macrophages when compared with non-activated macrophages. CONCLUSION: Upregulated chemokines were associated with macrophage recruitment and destruction of islet xenografts. PMID- 17344584 TI - [Expression of hCTLA4-Ig mediated by adeno-associated virus in porcine islets and their biological activity]. AB - OBJECTIVE: To evaluate the expression of hCTLA4-Ig and their biological function in newborn porcine islets (NPIs) transfected with AAV-hCTLA4-Ig. METHODS: Cultured NPIs were transfected with AAV-hCTLA4-Ig. The expression of CTLA4-Ig in these NPIs was assayed by RT-PCR and immunocytochemistry. The levels of IL-2, IFN gamma, and TNF-alpha in the culture medium were assayed by ELISA after these cells the co-cultured with human. The response of glucose-stimulated insulin secretion was observed in the transgene group and the control group. RESULTS: The expressions of CTLA4-Ig mRNA and protein were detected in the transgene group. The levels of cytokines were obviously lower in the transgene group than those in the control group (P<0.01). There was no significant difference in the response of glucose-stimulated insulin release between the transgene group and the control group (P>0.05). CONCLUSION: AAV mediated hCTLA4-Ig expression in NPIs could inhibit T lymphocyte to produce cytokines, while the endocrine functions of the NPIs were not significantly affected. PMID- 17344585 TI - [Effect of mono and combination therapy with FTY720 and ICAM-1 mAb for mouse-to rat cardiac xenotransplantation]. AB - OBJECTIVE: To observe the effect of FTY720 and ICAM-1 mAb mono and combination therapy in mouse-to-rat cardiac xenotransplantation. METHODS: Cardiac xenotransplantation was performed in abdominal site with micro-surgical technique. Recipients with xenografts were treated with different doses of FTY720 and/or ICAM-1 mAb. Graft survival, histopathology, infiltration of CD4+, and CD8+ T cells and levels of serum IL-2, IFN-gamma, IL-4, and IgM were investigated. RESULTS: Survival time of xenografts was (2.75+/- 0.43)d in the controls, survival of grafts treated with ICAM-1 mAb did not significantly improve. Treatment with large dose FTY720 led to a survival of (4.25+/- 0.71)d (P<0.01). Combination therapy with large dose FTY720 and ICAM-1 mAb achieved a significant prolongation of graft survival with (10.25+/- 2.12)d (P<0.01). Levels of serum IL 2, IFN-gamma and rat-anti-mouse IgM decreased in the combined therapy group. Pathologic lesion and infiltration of T cells in xenografts showed mitigated in the large dose combined therapy group. There was a significant negative correlation between the antibody level and the graft survival time (R=-0.754, P<0.01). CONCLUSION: The combined therapy of FTY720 and ICAM-1 mAb can achieve a significant effect in the prolongation of heart xenograft survival and inhibition of xenoantibodies. PMID- 17344586 TI - [Immune tolerance induced by combined heart-thymus transplantation for heart allograft in rats]. AB - OBJECTIVE: To explore the role of combined heart-thymus transplantation for heart allograft in rats. METHODS: Vascularized heart-thymus combined transplantation was performed with microsurgical technique. Graft survival, histopathology, infiltration of CD4+, CD8+ T cells, level and mRNA expressions of IL-2 and IL-4 in the serum and cardiac grafts were investigated. RESULTS: Heart allograft in the controls had a survival time of (6.0+/-0.76) d. heart-thymus combined transplantation in non-thymectomized rats had a survival time of (6.88+/-0.64)d (P<0.05). Heart-thymus combined transplantation in thymectomized rats led to an evident survival time of (14.13+/-5.82)d (P<0.01) for cardiac graft, which further obtained long term survival after short course of treatment with cyclosporine. Pathologic lesion and infiltration of CD4+ and CD8+ T cells in cardiac grafts showed mitigated in the long term survival group. IL-2 level in the serum and cardiac grafts maintained low level in the long term survival group, whereas IL-4 maintained high level. CONCLUSION: Whether thymectomized or not in recipient rats, heart-thymus combined transplantation has a positive effect to protect cardiac graft. Furthermore, in thymectomized rats heart-thymus combined transplantation may lead to evident survival prolongation of the heart grafts, which induces immune tolerance in short course of treatment with cyclosporine. PMID- 17344587 TI - [Effect of extract of ginkgo biloba leaves on the precondition of liver graft in rat liver transplantation]. AB - OBJECTIVE: To explore the effect of extract of ginkgo biloba leaves on the precondition of liver graft in rat liver transplantation. METHODS: Male Sprague Dawley rats were used as donors and recipients of orthotopic liver transplantation (OLT), and were randomly divided into extract of ginkgo biloba leaves group (Egb), NS control group (NS), and sham operation group (SO) according to whether the extract of ginkgo biloba leaves was injected by the venous (40 mg/kg) 1 h before the liver grafts harvesting. The rats were killed at 2 h, 6 h, and 24 h after the ischemia/reperfusion. The serum concentrations of ALT and AST were determined and the liver tissue were sampled to observe the expression of TNF-alpha and IL-1. RESULTS: After the ischemia/reperfusion the serum concentration of ALT and AST and expressions of TNF-alpha and IL-1 in the hepatic tissue in the NS group significantly increased (p<0.01), and the hepatocytic morphologic change was obvious compared with the SO group. The treatment of ginkgo biloba extract significantly decreased the serum concentration of ALT and AST and the expressions of TNF-alpha and IL-1 in the hepatic tissue in EGb group compared with the NS group (p<0.01), and relieved the hepatocyte swelling and necrosis. CONCLUSION: Ginkgo bilobA extract may decrease the release of TNF-alpha and IL-1 by inhibiting activation of kuffer cells and regulate the cell factors to protect the live. PMID- 17344588 TI - [Slowing progression of chronic allograft nephropathy by conversion from cyclosporin A to tacrolimus]. AB - OBJECTIVE: To investigate the feasibility and safety of substituting tacrolimus(FK506) for cyclosporin A(CsA) on delaying the pace of renal dysfunction in patients with biopsy-proven chronic allograft nephropathy(CAN). METHODS: Seventy-three renal transplantation patients with CAN proved by allograft biopsy were collected in this study. Patients were randomly divided into 2 groups. Patients were either converted to FK506(FK506 group, n=43) or remained on their initial CsA-based immunosuppression(CsA group, n=30). The clinical data at study entry and after 12 months including blood urea nitrogen(BUN), serum creatinine(SCr), glomerular filtration rate(GFR), 24-hour urine protein excretion, serum total cholesterol(TC), triglyceride(TG), low density lipoprotein(LDL) and the side effects of calcineurin inhibitors were monitored during a follow-up of over 12 months. RESULTS: Twelve months later, the level of SCr was statistically reduced and GFR levels were obviously elevated in the FK506 group as compared with CsA group [(194.8+/-42.5)micromol/L vs. (245.4+/ 52.8)micromol/L and (50.14+/-3.92)mL/(min.1.73 m(2)) vs. (40.58+/ 2.49)mL/(min.1.73 m2), P<0.01]. Quantity of 24-hour urine protein excretion in the FK506 group was (2.0+/-0.5)g which is significantly lower than (3.9+/-0.7)g in the CsA group(P<0.01). TC, TG, and LDL levels remained unchanged in the CsA group, while those were statistically reduced in the FK506 group respectively [(5.19+/-0.73)mmol/L vs. (6.94+/-1.37)mmol/L, (1.86+/-0.84)mmol/L vs. (3.14+/ 1.38)mmol/L, (3.03+/-0.71)mmol/L vs. (3.82+/-0.89)mmol/L, P<0.01]. Tremor obviously increased (P<0.01) and hypertension obviously decreased (P<0.05) in the FK506 group compared with the CsA group. CONCLUSION: FK506 treatment can greatly improve the proteinuria and hyperlipidemia. Conversion from CsA to FK506 is an effective and safe alternative therapy for delaying the progression of renal dysfunction induced by CAN. PMID- 17344589 TI - Two conditional media promoting the differentiation murine embryonic stem cells into hematopoietic stem cells. AB - OBJECTIVE: To derive hematopoietic stem cells with functional properties of hematopoietic reconstitution from murine embryonic stem (ES) cells. METHODS: ES D3 cells by formation of the day-4 embryoid bodies (4dEBs) were induced into hematopoietic stem cells by co-culture with murine bone marrow endothelial cell conditional medium (mBMEC-CM) and the fetal liver stromal cell-conditional medium (FLSC-CM). This experiment was designed to 4 groups (mBMEC-CM + FLSC-CM group, mBMEC-CM group, FLSC-CM group, and the control group). RESULTS: The total cell numbers, CD34+ cell numbers, and colony numbers formed in the mBMEC-CM+FLSC-CM group were the highest among the 4 groups. The cells in the mBMEC-CM + FLSC-CM group resumed the hematopoietic system of the mice after being transplanted with the inducing cells. CONCLUSION: The culture condition combing mBMEC-CM with FLSC CM can promote murine ES cells differentiating into hematopoietic stem cells with functional properties of hematopoietic reconstitution. PMID- 17344590 TI - [Protective effect of abnormal savda munzip on radiation-induced damage in mice]. AB - OBJECTIVE: To investigate the protective effect of abnormal savda munzip on the radiation-induced damaged in mice. METHODS: The mice were randomly divided into 2 groups: a control group and a drug group; the latter was again divided into a low dosage group (6.25%), a moderate dosage group (12.5%) and a high dosage group (25%) according to the drug concentration. All mice were given general radiation emitted by 6 Gy MV-X liner accelerator once, which resulted in the acute radiation damage. The different administrations of abnormal savda munzip were fed to the mice in the drug group orally for 7 days consecutively before and after the radiation. On the day of the last administration, 10 mice were sacrificed, and white blood cells, red cells and blood plates of the peripheral blood, spleen index, and spleen SOD were detected; while the 20 remaining mice were fed continually till 30 days, and the 30 day survival ratio of the mice was calculate. RESULTS: (1) Although the mice weight in the drug groups was higher than that in the control group, no significant difference existed (P>0.05). Spleen index in the control group was higher than that in the drug group. (2) Spleen SOD was significantly increased by the drugs compared with that of the control group (P<0.01), which was positively related to the drug concentration. (3) Pre-treatment of mice with the extract of abnormal savda munzip significantly increased the white cells and red cells in the peripheral blood compared with the control group (P<0.05). The blood cells were positively related to the drug concentration (P<0.05). Although the counts of blood plates in all drug groups were higher than those in the control group, no significant difference existed (P>0.05). (4) Compared with the control group, a marked improvement of 30 day survival rate in all drug groups was observed (P<0.0001). Both the concentration and the survival rate were increased (P<0.01). (5) The SOD level and leukocyte counts in the irradiated mice were positively related to the survival ratio (r=0.612, P<0.005; r=0.32, P<0.05, respectively). CONCLUSION: The abnormal savda munzip has significant protective function on the mice irradiated by 7 Gy MV-X liner accelerator. PMID- 17344591 TI - [Sequence polymorphism of the promoter region of gene STK11 in patients with Peutz-Jeghers syndrome]. AB - OBJECTIVE: To explore the relationship between the sequence variation of the promoter region (-1543 approximately -1160) of STK11 gene and the risk of developing Peutz-Jeghers syndrome (PJS). METHODS: The sequences of the promoter region of 14 PJS patients (7 patients are inherited and the other 7 patients are sporadic) and 42 normal individuals were PCR amplified and then sequenced. RESULTS: A new single nucleotide polymorphism (SNP) G/T (-1275) in STK11 promoter region was identified. The frequency of genotype GG, GT, and TT was 53.3%, 26.7%, and 20%, respectively among PJS patients and 33.3%, 64.3%, and 2.4%, respectively among the normal individuals. The frequency of genotype GG and TT among patients was significantly higher than that among the normal individuals, and the frequency of genotype GT among patients was significantly lower than that among the normal individuals (chi(2)=8.521, P<0.05). CONCLUSION: G/T(-1275) in STK11 promoter region is a new SNP. The genotype of this new SNP may relate to the risk of developing Peutz-Jeghers syndrome (PJS) deserve further research. PMID- 17344592 TI - [Experimental study of acute lung injury induced by glutamate in vivo]. AB - OBJECTIVE: To investigate the possible injury induced by glutamate in the lung. METHODS: The lung wet weight/body weight (LW/BW), lung wet/dry weight (W/D), the content of cells and the total protein (TP) in bronchoalveolar lavage fluid (BALF) were determined together with the micromorphology observation. RESULTS: (1) The LW/BW, W/D, the content of white blood cells, red blood cells and TP in BALF increased in a dose dependent manner 2 hours after the administration of the glutamate (0.50 - 0.75 g/kg). (2) Examination of histological sections showed the presence of lung inflammation charactered by neutrophils recruitment 2 hours after the glutamate administration. (3) The increase of W/D caused by glutamate (0.50 g/kg) was nearly abolished by pre-treatment with MK801 (a specific blocker of NMDA receptor, 0.1 mg/kg) for 30 minutes (P<0.05). CONCLUSION: Glutamate can cause the acute lung injury through the activation of NMDA receptor in vivo. PMID- 17344593 TI - [Effect of catechin microcapsule on the repair of DNA damage in glomerular mesangial cells induced by H2O2]. AB - OBJECTIVE: To explore the effect and possible mechanism of catechin microcapsulation on the repair of DNA damage in glumreular mesangial cells (GMCs) induced by H2O2. METHODS: According to H2O2 concentration, the experiment GMCs were divided into 6 groups: a control group, 50 micromol/L group, 100 micromol/L group, 150 micromol/L group, 200 micromol/L group and 250 micromol/L group. Each group was sub-divided into 3 groups: 6 h group, 12 h group and 24 h group, in order to determining the optimum dose and the best time of detecting the DNA damage in GMCs. The cultured cells were divided into 8 groups as follows: the NS control group, the H2O2 group, the catechin groups (the final concentrations were 10.0, 15.0, and 20.0 mg/L respectively) and the various catechin microcapsulation groups (the final concentrations were 10.0, 15.0, and 20.0 mg/L respectively). At the end of the experiment, hydroxy radical (OH), malonydialdehyde (MDA) and total superoxide dismutase (tSOD) concentration of supernadant in GMCs were determined by biochemistry assay, the repair of DNA damage in GMCs were detected by single cell gel electrophoresis assay. RESULTS: (1)At 6th h, H2O2 of 100 micromoL/L could cause the DNA damage of GMCs, and H2O2 of 150 micromol/L could result in DNA damage significantly. (2) No difference was found in the comet span of GMCs DNA in the catechin group and catechin microcapsulation group of different concentrations, while the DNA comet tail-long in the catechin microcapsulation group was shorter than that of the catechin group(all P(s)<0.05), and the fluorescence intensity of tail in the catechin microcapsulation group was lower than that of the catechin group(all P(s)<0.01). (3)When the concentration of catechin was 10.0 mg/L, no statistical significance was obtained in the concentration of dOH-, MDA and tSOD between the catechin microcapsulation group and the catechin group; while dOH- and MDA concentrations were lower, and the tSOD was higher in the catechin microcapsulation group than that in the catechin group when the concentration of catechin was 15.0 mg/L and 20.0 mg/L(all P(s)<0.05). CONCLUSION: Catechin microcapsulation can enhance the GMCs ability of repairing DNA damage,which may be due to elevating the capacity of its anti oxidation by catechin microcapsulation. PMID- 17344594 TI - [Effects of Fuzhengyangying granules on the bone marrow proliferation and bcl-2 expression in mice with immune mediated aplastic anemia]. AB - OBJECTIVE: To explore the effect of Fuzhengyangying granules (FZYYG) on the expression of the bone marrow proliferation and bcl-2 in mice with immune mediated aplastic anemia. METHODS: Forty BALB/c mice were randomly allocated to 4 groups: a normal control group, a model group, cyclosporine A (CSA) group and FZYYG group. The model group was fed with physical salt, while the CSA and FZYYG group were fed with CSA and FZYYG respectively, and then the changes of peripheral hemoglobin (Hb), platelet, bone marrow nucleus cell (BMNC), bone marrow hematopoiesis tissue volume and bcl-2 expression were examined. RESULTS: The count of Hb, the platelet, BMNC, the bone marrow hematopoiesis tissue volume and the bcl-2 positive rate in the model group were lower than those in the normal group (P<0.05), whereas the count of Hb, the platelet, BMNC, the bone marrow hematopoiesis tissue volume and the bcl-2 positive rate in both CAS and FZYYG groups were significantly higher than those in the model group (P<0.05). CONCLUSION: FZYYG can induce the bcl-2 antigen expression and postpone the haematogenous cells apoptosis, and it is effective for mice with immune mediated aplastic anemia. PMID- 17344595 TI - [Differentiation of QY1 bone marrow pluripotential mesenchymal stem cell line cells into cardiomyocytes and vascular endothelial cells in vitro]. AB - OBJECTIVE: To explore the differentiation potential of QY1 bone marrow mesenchymal stem cell (MSCs) line cells into cardiacmyocytes and vascular endothelial cells in vitro, to optimize the suitable conditions of MSCs differentiating into cardiomyocytes in vitro, and to examine the potentials of MSCs differentiating into cardiomyogenesis and vasculogenesis. METHODS: Specifically committed differentiation inductive medium was employed, including 5 azacytidine for cardiomyogenesis and vascular endothelial growth factor for vasculogenesis in culture respectively in vitro. The differentiated cells were identified by immunohistochemistry and molecular biology. RESULTS: MSCs line cells had been cultured in the normal culture medium for 72 hours, then the differentiation inductive medium including 10 micromol/L 5-azacytidine was added into the normal culture dishes for 24 hours only. After that the culture medium was changed back to the normal culture medium. Normal culture medium was changed every 7 days. The second induction was performed after 14 days. The differentiated cells treated with 5-azacytidine could beat spontaneously and formed myotube structures in the optimal induction conditions, and the differentiation rate was (39.47+/-0.56)%. The differentiated cells expressed specific cardiomyocytic proteins identified by the positive immunohistochemistry staining with anti-alpha-sarcomeric antibody and anti-Cx-43 antibody, and also expressed the alpha-myosin heavy chain examined by RT-PCR. The differentiated cells began to appear as the lined up vascular endothelial cells after 48 hour treatment with vascular endothelial growth factor. Some of the differentiated cells connected each other to form vascular endothelial web-like structure after 7 day treatment with vascular endothelial growth factor. On 14 d after treating with vascular endothelial growth factor, the differentiated cells were identified by immunohistochemistry staining. The expressions of both specific surface antibody CD31 and factor VIII for vascular endothelial cells were positive. CONCLUSION: The cells of QY1 bone marrow mesenchymal stem cell line may differentiate into cardiomyocytes or vascular endothelial cells in vitro under specific condition. PMID- 17344596 TI - [Inhibition of cell growth and induction of apoptosis in human hepatoma cell line HepG2 by tanshione IIA]. AB - OBJECTIVE: To determine the effect of tanshinone IIA on the growth and apoptosis in human hepatoma cell line HepG2. METHODS: The human hepatoma cell line HepG2 was treated with tanshinone IIA at various concentrations for 72 h. The inhibition of proliferation was measured by MTT assay and apoptosis-related alterations in morphology measured by cytochemical staining (HT33258). DNA fragmentation was evaluated by agarose gel electrophoresis. Apoptotic rate and cell arrest were quantified by flow cytometry (FCM). RESULTS: Tanshinone IIA inhibited the growth of HepG2 in a time- and dose- dependent manner. The semi inhibitory concentration (IC50) value after the treatment with tanshinone IIA on HepG2 for 24, 48 and 72 h were 14.7, 7.4, and 3.9 microg/ mL, respectively. After the treatment with 0.5 - 10 microg/mL tanshinone IIA for 72 h, the formation of apoptotic bodies was observed. DNA ladder was shown in agarose gel electrophoresis, in addition to the cells treated by 1.0 microg/mL tanshinone IIA . The apoptotic rates at 0.5, 1.0, 2.0, 5.0, and 10.0 microg/mL for 72 h were 20.32%+/-2.16%, 28.0%+/-2.35%, 33.87%+/-3.43%, 46.73%+/-4.08% and 57.85%+/-3.74%, respectively, which were all significantly higher than those of the control group (P<0.05). CONCLUSION: Tanshinone IIA can inhibit the proliferation of human hepatoma cell line HepG2 in a time- and dose- dependent manner, and the mechanism of growth inhibition of human hepatoma cells may be related to the induction of apoptosis. PMID- 17344597 TI - [Effect of integrin-linked kinase on renal tubular epithelial cell transdifferentiation in diabetic rats]. AB - OBJECTIVE: To determine the effect of integrin-linked kinase(ILK) in renal tubular epithelial cells and its relation to tubular epithelial-myofibroblast transdifferentiation. METHODS: Wistar rats were randomly divided into 3 groups, Group normal control (n=10), Group diabetic without therapy(n=10) and Group diabetic with Losartan 20mg/(kg . d)(n=10). Five rats were killed in each group at the 8th and 16th week. The left kidneys were kept for HE and Masson staining to observe the pathological variations in the renal interstitium. ILK, alpha-SMA and Vimentin in renal tubular epithelial cells were detected by immunohistochemistry analysis. RESULTS: Compared with the control group, ILK, alpha-SMA and Vimentin in renal tubular epithelial cells in Group diabetes gradually increased in immunohistochemistry (P<0.01); ILK was consistent with the pathological variation of renal interstitium and was positively correlated to alpha-SMA(rs=0.621, P<0.05). In comparison with the Group diabetes, the expression of ILK, alpha-SMA and Vimentin in renal tubular epithelial cells was apparently declined (P<0.01) in Group diabetes with Losartan. CONCLUSION: Tubular epithelial myofibroblast transdifferentiation and the over-expression of ILK, between which there may be significant connections, are important events in the progression of diabetic nephropathy. Losartan, a blocker of angiotension II type I receptor, which may down-regulate the expression of ILK in diabetic renal tubular epithelial cells, can restrain the procession of epithelial-myofibroblast transdifferentiation. PMID- 17344598 TI - [Expression of KiSS-1mRNA in pancreatic ductal adenocarcinoma and non-cancerous pancreatic tissues in SD rats]. AB - OBJECTIVE: To establish a model of pancreatic cancer in Spragu-Dawely (SD) rats, and to examine the expression level of KiSS-1mRNA in pancreatic cancer and non cancerous pancreatic tissues in SD rats. METHODS: Dimethylbenzanthracene (DMBA) was directly implanted into the parenchyma of pancreas in SD rats (Group A), and DMBA combined with trichostatin (TSA) was implanted in the intervention group (Group B). The carcinogenesis of rats executed within 3 - 5 months in Group A and Group B were observed by HE staining and macrography. Meanwhile, the rats in the control (Group C) were executed in 5 months. The expression of KiSS-1mRNA was assayed by in situ hybridization. RESULTS: (1) The incidence of pancreatic cancer in Group A within 3 - 5 months was 48.7% (18/37), including 17 cases of pancreatic ductal adenocarcinoma and 1 case of fibrosarcoma. The incidence of pancreatic cancer in Group B was 33.3% (12/36), including 11 pancreatic ductal adenocarcinoma and 1 fibrosarcoma. The maxial diameter of tumor mass in Group A was higher than that in Group B (P<0.05). (2) The positive rates of KiSS-1 mRNA in pancreatic cancer in Group A and Group B were significantly lower than those in non cancerous pancreatic tissues in Group A and Group B (P<0.01). The positive rates of KiSS-1mRNA in Group A or Group B with ductal adenocarcinoma were significantly lower than those in Group A or Group B without ductal adenocarcinoma (P<0.01). The middle or severely atypical ductal hyperplasia was observed in non-cancerous pancreatic tissues with the negative KiSS-1mRNA. CONCLUSION: DMBA directly implanted into the parenchyma of pancreas can obtain an ideal pancreatic cancer model with high incidence in a short time. TSA may have an inhibitive effect on the carcinogenesis and the growth of pancreatic ductal adenocarcinoma in rats, and KiSS-1 may play an important role in inhibiting the invasion and metastasis of pancreatic cancer. PMID- 17344599 TI - [Rat dental papilla cell culture with nanometer-HAP in vitro]. AB - OBJECTIVE: To determine the effects of nano-hydroxyapatite(nano-HAP)on the proliferation and activity of rat dental papilla cells(RDPCs)in vitro, and to evaluate the feasibility of using nano-hydroxyapatite(nano-HAP)as dental papilla cell scaffold in dental tissue engineering. METHODS: RDPCs cultured with the porous nano-HAP in vitro served as the experimental group, and the routine culture of RDPCs in flasks served as the control. Scanning electronic microscope was used to observe the growth and adherence of the RDPCs to nano-HAP. Cell proliferation, cellular protein content, and alkaline phosphatase(ALP) were detected to assess the cellular activities. RESULTS: RDPCs proliferated well, and adhered to the outer and inner surface of the nano-HAP scaffold. Compared with the control group, cells in the experimental group presented higher proliferation on 6 d and 8 d and higher cellular protein content on 6 d and 9 d. No significant difference was detected in the ALP activity in the 2 groups. CONCLUSION: RDPCs seeded into nano-HAP grow better and have more vigorous cellular activity, suggesting that nano-HAP has excellent biocompatibility with dental papilla cells, and it can serve as a promising scaffold for dental tissue engineering. PMID- 17344600 TI - [Effect of Th1/Th2 cytokine immune imbalance on the expression of nerve growth factors in asthma]. AB - OBJECTIVE: To explore the effect of Th1/Th2 cytokines on the expression of nerve growth factor(NGF)in splenic lymphocytes in asthmatic model. METHODS: Four SD rats were sensitized and challenged with ovalbumin to establish an asthmatic model, and the rat splenic lymphocytes were isolated and cultured with ConA. The expressions of NGF mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and were observed after the lymphocytes were exogenously added with interferon-gamma(IFN-gamma) or interleukin-4 (IL-4). RESULTS: The lymphocytes of the asthmatic model stimulated by ConA in vitro expressed NGF mRNA in a time-dependent manner. After the lymphocytes had been cultured with IL-4 for 12 h, 24 h, 36 h, and 48 h, 50 microg/L IL-4 upregulated the expressions of NGF mRNA in a time-dependent manner and all the NGF mRNA expressions were significantly higher than the basal values at the same time(all Ps<0.01). After 0, 10, 50, and 100 microg/L IL-4 had been added for 24 h, IL-4 upregulated the expressions of NGF mRNA in a dose-dependent manner and the NGF mRNA expressions were all significantly higher than the values of the lower dose IL-4(all Ps<0.05). After the lymphocytes had been cultured with 10 mug/L IFN-gamma for 0 h, 12 h, 24 h, 36 h, and 48 h, IFN-gamma downregulated the expressions of NGF mRNA in a time-dependent manner and all the NGF mRNA expressions were significantly lower than the basal values at the same time(all Ps<0.01). After 0, 1, 10, and 50 microg/L IFN-gamma have been added for 24 h, IFN-gamma downregulated the expressions of NGF mRNA in a dose-dependent manner and all the NGF mRNA expressions were significantly lower than the values of the lower IFN gamma dose(all Ps<0.05). CONCLUSION: In the splenic lymphocytes of asthmatic rats, IL-4, one of the Th2 cytokines, can upregulate the expressions of NGF; IFN gamma, one of the Th1 cytokines, can downregulate the expressions of NGF both in a time-dependent manner and in a dose-dependent manner. Th1/Th2 cytokine immune imbalance may indirectly induce the airway neurogenic inflammation by regulating the NGF mRNA expression. PMID- 17344601 TI - [Microsurgical treatment of giant epidermoid cysts in the central region of the skull base]. AB - OBJECTIVE: To explore microsurgical treatment of giant epidermoid cysts in the central region of the skull base in 36 cases. METHODS: The clinic characteristics and the operation experience about the microsurgical treatment of giant epidermoid cysts in the central region of the skull base were retrospectively analyzed. RESULTS: In the 36 cases, 32 had total removal of the tumor, and the other 4 experienced subtotal removal. Thirteen presented nerve system damage or nerve damage aggravation, but there was no operative mortality. CONCLUSION: According to the epidermoid cyst area, the ratio of total resection can be elevated and the complication can be lowered by suitable approach and microneurosurgical technique. PMID- 17344602 TI - [Effects of BIS and AEPindex monitoring on the depth of anesthesia in in intravenous-inhalational anesthesia anesthesia]. AB - OBJECTIVE: To evaluate the effects of bispectral index(BIS) and auditory evoked potentials index(AEPindex) monitoring on the depth of anesthesia in inhalation of isoflurane and target-controlled infusion(TCI) of propofol, and to observe the changes of BIS and AEPindex. METHODS: Fourty ASA physical status I - II patients undergoing selective abdominal operations were divided into 2 groups randomly: Group I1(the end-tidal isoflurane concentration was 0.6 MAC, n=20) and Group I2(the end-tidal isoflurane concentration was 1.0 MAC, n=20). Anesthesia was induced with proprofol and vecuroninm. After the tracheal intubation, the patients were ventilated with 0.6/1.0 MAC isoflurane in pure oxygen, and after 20 minutes, propofol was administered with TCI according to the different target plasma concentrations from 1.0 g/mL to 3.0 g/mL(increasing 0.5 g/mL each time). The changes of MAP, HR, BIS and AEPindex were recorded simultaneously. RESULTS: There was no close correlation between MAP, HR and the end-tidal isoflurane concentration, target plasma concentration of propofol. The correlation coefficiencies between BIS, AEPindex and the end-tidal isoflurane concentration were -0.757, -0.819 and -0.832, -0.878 (P<0.001), respectively; those between BIS, AEPindex and the target plasma concentration of propofol were -0.932, -0.888 and -0.920, -0.923 (P<0.001). The correlation coefficiencies between BIS, AEPindex and the stimulation of endotracheal intubation were -0.728 and 0.544, respectively; however, there was no close correlation between BIS , AEPindex and the stimulation of skin incision, and exploration. CONCLUSION: BIS and AEPindex are reliable parameters to monitor the depth of anesthesia of isoflurane and propofol combined anesthesia; and in response to the stimulation of tracheal intubation, AEPindex is better than BIS, but BIS and AEPindex can not be used to predict the cardiovascular reaction of skin incision and exploration. PMID- 17344603 TI - [Antisense c-fos oligonucleotides-induced myopia in guinea pigs]. AB - OBJECTIVE: To characterize the antisense c-fos oligonucleotides that control the expression of immediate-early gene c-fos in retina in order to better understand the mechanism by which antisense c-fos oligonucleotides induced myopia. In this study the signal transduction in the pathway linking visual experience and the regulation of the eye's growth was investigated. METHODS: Thirty-one 3-week guinea pigs were assigned into 3 groups: antisense and sense c-fos oligonucleotides were intravitreally injected every 3 days to the eyes of the experimental guinea pigs at different concentrations; and saline vehicle to control guinea pigs in the same way. The refraction and axial length of the eyes were measured before and after the treatment, and the immediate-early gene c-fos expression in the retina was quantified by immunohistochemistry and RT-PCR. RESULTS: The moderate myopia was induced in high (1 nmol) and low (0.1 nmol) level of antisense c-fos oligonucleotide intravitreous injection (-5.425 D and 5.575 D, respectively) compared with the control ateral eyes. The refraction and axial length of the treated eyes increased, and the expression of immediate-early gene c-fos decreased significantly in the antisense c-fos oligonucleotides intravitreously injected eyes compared with the sense c-fos oligonucleotide intravitreously and saline vehicle injected eyes (P<0.01). The refraction and axial length were of no statistically significant differences among the sense c fos oligonucleotides-treated eyes and saline-treated eyes and non-treated eyes (P>0.05). CONCLUSION: The obvious myopia can be induced by antisense c-fos oligonucleotides in guinea pigs; antisense c-fos oligonucleotides inhibit c-fos expression in the retina. Immediate-early gene c-fos may be a potential factor in the prevention of myopia and plays an important role in the signal transduction of the retina. PMID- 17344604 TI - [New classification for adenocarcinoma of the esophagogastric junction in China]. AB - OBJECTIVE: To determine the clinical application of the new classification of adenocarcinoma of esophagogastric junction (AEG). METHODS: The data of cancer of distal esophagus, cancer of cardia, and proximal gastric cancer were reviewed. Clinicopathologic characteristics, surgical modes and survival were analyzed according to Siewert's standards. RESULTS: Among the 203 patients that were up to the standard, 29 had adenocarcinoma of the distal esophagus (Type I), 80 had true carcinoma of cardia (Type II), and 94 had subcardial carcinoma (Type III). The 5 year survival rates of the 3 types of patients after the operation were 34% for Type I, 27.5% for Type II, and 24.5% for Type III (P<0.05). Further analysis of the patients with curative resection suggested there was no significant difference in the 5-year survival rates, with 37.5% for Type I, 34.5% for Type II, and 33.3% for Type III (P>0.05). CONCLUSION: Difference has been found in the clinicopathologic characteristics of the 3 types of adenocarcinoma of the esophagogastric junction. The exact relation of the 3 types is still unknown. The TNM classification, complete tumor resection and the extent of lymph node metastasis are critical for the prognosis of the patients. PMID- 17344605 TI - [Therapeutic effect of compositive rehabilitation on lumber disc herniation]. AB - OBJECTIVE: To observe the curative effect of different physical rehabilitation techniques on patients with lumbar disc herniation. METHODS: Eighty-four patients were randomly divided into Group A, Group B and Group C. Group A were treated with the computerized pelvis traction and ultrashort wave, Group B were treated with the computerized pelvis traction only, while Groups C were treated with the computerized pelvis traction, the ultrashort wave and the traditional Chinese medicine iontophoresis. The outcome was measured with the Japanese Orthopaedics Association Score (JOA score) about lower back pain (LBP). RESULTS: Compared with before the treatment, the JOA score of all the 3 groups increase markedly after the treatment (P<0.001). Compared with group B, the JOA score of Groups A and Group C significantly increased (P<0.05). Compared with Group A, the JOA score in Group C significantly increased (P<0.05). CONCLUSION: The curative effect of comprehensive rehabilitation on lumbar disc herniation is better than that of the single rehabilitation. PMID- 17344606 TI - [Operative strategy of the thoracolumbar fracture dislocation]. AB - OBJECTIVE: To explore the operative strategy and clinical outcome of the thoracolumbar fracture dislocation. METHODS: Forty-two patients with the thoracolumbar fracture dislocation were treated with anterior approach (10 patients), posterior approach (28 patients), and anterior combined with posterior approach (4 patients) in order to construct the stabilities of the spine. The ASIA grades were used to evaluate the recovery of the neurological function, and the improvement of the kyphosis deformities was evaluated by the cobb's angle post-operation. RESULTS: All the patients had no complications of injury in the vascular and neurological system. The ASIA grades after the operation were superior to those of pre-operation, and the cobb's angle was rectified distinctly. CONCLUSION: When appropriate operative strategies are adopted, thoracolumbar fracture dislocation can be treated with satisfactory outcome. PMID- 17344607 TI - [Mechanical valve replacement in children with heart valve diseases]. AB - OBJECTIVE: To determine the surgical point and technique of artificial mechanical valve replacement in children with heart valve diseases. METHODS: From Jan. 1989 to Oct. 2005, 63 children under 15 years received mechanical cardiac valve replacement with cardiopulmonary bypass (CPB). RESULTS: The valve replacement included aortic valve replacement in 20 children, mitral valve replacement in 37 children and combined aortic valve and mitral valve replacement in 6 children. CONCLUSION: The operation mortality was 7.94%(5/63). The follow-up periods were from 4 months to 204 months. The late mortality was 10.34%(6/58). All the other children were in NYHA class I - II. The operation mortality of children with heart valve replacement is higher than that of adults, but it was very effective. PMID- 17344608 TI - [Peripheral vascular complications after the cardiac catheterization]. AB - OBJECTIVE: To explore the cause, the clinical manifestation and the management of peripheral vascular complications after cardiac catheterization. METHODS: Clinical data of patients with peripheral vascular complications were analyzed retrospectively. RESULTS: Of the 4,531 patients, 122 (2.7%) had peripheral vascular complications, including local hematoma (86 cases, 1.90%), pseudoaneurysm (15 cases, 0.33%), arteriovenous fistula (8 cases, 0.18%), femoral venous thrombosis (5 cases, 0.11%), excessive hemorrhage (5 cases, 0.11%), femoral arterial thrombosis (2 cases, 0.04%), and femoral nerve malfunction (1 case, 0.02%). All complications were relieved after conservative therapy except that one case needed surgery. CONCLUSION: Peripheral vascular complications are associated with anticoagulation, diabetes, and hypertension. Prognosis of overwhelming complications is good, as long as patients are treated timely and appropriately. PMID- 17344609 TI - [Medical thoracoscopy in the diagnosis of complicate pleural effusion]. AB - OBJECTIVE: To evaluate the role of medical thoracoscopy in the diagnosis of the pleural effusion of unknown etiology. METHODS: The results of 36 patients with the pleural disease of unknown etiology diagnosed by medical thoracoscopy were retrospectively analyzed, including the pathologic results and the complications. RESULTS: Among the 36 patients, 35 were determined with positive rate of 97.2%, and no serious complications was found. CONCLUSION: Medical thoracoscopy is an important method of diagnosing complicate pleural effusion, and has high positive rate. It is a simple operation, with no serious complication, and fast recovery. PMID- 17344610 TI - [Immediate or elective PCI after coronary angiography]. AB - OBJECTIVE: To compare the success rate and the complication rate of immediate percutaneous coronary intervention (PCI) and elective PCI after coronary angiography(CAG), and to estimate the clinical value of immediate PCI. METHODS: One-hundred fifteen patients who underwent immediate PCI after CAG were enrolled into the immediate group, and 172 patients on whom PCI and CAG were performed on 2 days were enrolled into the elective group in Second Xiangya Hospital of Central South University during 2005. The clinical manifestations, lesion vessel characteristics, and length and diameter of stents in the 2 groups were similar. Lesion vessels were defined as Type A, B, and C according to the standard of ACC/AHA in 1988. RESULTS: The success rate and the complication rate of Type A and B lesion were not significantly different in the 2 groups (P>0.05). The success rate of Type C lesion in the immediate group was lower than that in the elective group (P<0.01). The complication rate of Type C lesion in the immediate group was higher than that in the elective group (P<0.05). CONCLUSION: Type A and B lesions may undergo immediate PCI, while Type C lesion is not suitable to be performed immediately PCI after CAG. Immediate PCI after CAG has some clinical value. PMID- 17344611 TI - [Measurement of activated clotting time during cardiopulmonary bypass in infective endocarditis patients]. AB - OBJECTIVE: To investigate the proper dosage of heparin and protamin in treating the patients with infective endocarditis (IE) during the operation. METHODS: Activated clotting time (ACT) was measured during and after cardiopulmonary bypass (CPB) in 30 patients with IE and 30 patients with rheumatic heart disease (RHD) respectively. RESULTS: The dosage of heparin before bypass in IE group was significantly higher than that of RHD group (P<0.05); the dosage of protamin for neutralization after bypass in IE group was significantly higher than that of RHD group (P<0.05); the ratio of protamin and heparin were 0.76 +/-0.23 in IE group and 0.74 +/-0.12 in RHD group (P>0.05). CONCLUSION: The dosage of protamin should be increased to 3 mg/kg as the heparin is over 400 U/kg before CPB in the patient with IE, but the ratio of protamin and heparin will not be obviously changed. PMID- 17344612 TI - [Color Doppler flow image of Budd-Chiari syndrome]. AB - OBJECTIVE: To evaluate the diagnostic value of color Doppler flow image (CDFI) for the diagnosis of Budd-Chiari syndrome (B-CS). METHODS: CDFI findings of 35 patients with B-CS were retrospectively analyzed and compared with the findings of venography of inferior vena cava (IVC). RESULTS: Thirty-four patients were diagnosed as B-CS by CDFI, while one patient with local tunica stenosis was misdiagnosed. The correct diagnostic rate was 97.1%. In the 34 patients, CDFI displayed stenosis or occlusion in the hepatic vein and IVC in 24 patients, IVC only in 8,and hepatic vein only in 2. CONCLUSION: CDFI may be a principal non invasive technique to diagnose B-CS. PMID- 17344613 TI - [Analysis of 94 cases of IgA nephropathy in children]. AB - OBJECTIVE: To evaluate the clinical and pathological features of 94 children suffering from IgA nephropathy (IgAN) while estimating the prevalent situation in Hunan province. METHODS: To summarize the annual number of hospitalized children, those with kidney diseases, those accepted biopsy, and those confirmed as IgAN in both Xiangya Hospital and Second Xiangya Hospital undertaking kidney biopsy in Hunan province during 1995 and 2004. RESULTS: In the past 10 years, as the hospitalized population in both hospitals accrued to 9.98% each year. The rate of 7.5% was seen in those with kidney diseases. Among whom 56.3% accepted kidney biopsy and 94 of them were confirmed as IgAN. Hematuria was the main clinical presentation, seen in 71 cases, accounting to 76%, and even to 98% after excluding those with nephrotic syndrome and isolating proteinuria type of IgAN. Inflammation infiltration (91%), renal tubule degeneration (81%), and renal interstitial fibrosis (31%) were the major pathological features of 94 children, especially in nephrotic syndrome IgAN. CONCLUSION: The number of children with IgAN synchronously accrues as hospitalized population, those with kidney diseases, and those by kidney biopsy. Hematuria is the major symptom. To routinely perform urine analysis and kidney biopsy in asymptomatic hematuria may improve the diagnosis. Inflammation infiltration, renal tubule degeneration, and renal interstitial fibrosis are the major pathological features in IgAN children, especially in nephrotic syndrome IgAN, probably relating to continuous proteinuria. Early control of proteinuria may delay or decrease renal tubule fibrosis. PMID- 17344614 TI - [Cefoxitin disk diffusion test in the detection of MRS heterogenic drug-resistant strains]. AB - OBJECTIVE: To evaluate the reliability and clinical practicability of cefoxitin disk diffusion test in the detection of methicillin-resistant staphylococcus (MRS) heterogenic drug-resistant strains. METHODS: Three hundred and ten strains of staphylococcus isolated from clinics were detected by the oxacillin disk diffusion test, the cefoxitin disk diffusion test as well as the oxacillin agar dilution test according to the standard operation procedures of NCCLS, and the detection of mecA gene of staphylococcus was used as a criterion. The sensitivities and specitivities of the 4 methods were compared. RESULTS: By the detection of mecA gene, the ratio for MRSA was 57.1%(113/198) and the ratio for MRCNS was 62.5%(70/112). Both the sensitivity and specificity of cefoxitin disk diffusion test in the detection of MRS were 100%, and those in the detection of MRCNS were 98.6% and 100%. CONCLUSION: Cefoxitin disk diffusion test is reliable, simple and convenient, and it can be used as a conventional method for the detection of MRS in clinical laboratories. PMID- 17344615 TI - [Function and gene expression of the active efflux transporters in drug-resistant Candida albicans]. AB - OBJECTIVE: To investigate the function and gene expression of active efflux transporters in drug-resistant candida albicans. METHODS: The broth microdilution method was performed to determined the minimal inhibitory concentration of 4 antifungal drugs to 20 candida albicans. We compared the efflux of Rhodamine 6G between sensitive and some of fluconazole-resistant candida albicans, and screened out the resistant strains with significantly increased efflux of Rhodamine 6G. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure the mRNA levels of active efflux gene CDR1 and CDR2. RESULTS: The efflux of Rhodamine 6G was significantly increased in some fluconazole-resistant strains when glucose was added, and the gene expressions of CDR1 and CDR2 were also obviously increased, compared with those in the sensitive strains. CONCLUSION: The excessive expression of active efflux pump gene is related to the resistance to fluconazole in candida albicans. The measurement of Rhodamine 6G efflux is a useful method for the identification of drug-resistant strains induced by the excessive expression of active efflux pump. PMID- 17344616 TI - [A case of sulpiride induced rhabdomyolysis and acute renal failure]. PMID- 17344617 TI - [A case of pregnancy complicated with rheumatic heart disease, cerebral embolism and rheumatic sacroilioarthritis]. PMID- 17344618 TI - Reliability of linear distance measurement for dental implant length with standardized periapical radiographs. AB - The purpose of this study was to investigate the accuracy of distance measurements of implant length based on periapical radiographs compared with that of other modalities. We carried out an experimental trial to compare precision in distance measurement. Dental implant fixtures were buried in the canine and first molar regions. These were then subjected to periapical (PE) radiography, panoramic (PA) radiography, conventional (CV) and medical computed (CT) tomography. The length of the implant fixture on each film was measured by nine observers and degree of precision was statistically analyzed. The precision of both PE radiographs and CT tomograms was closest at the highest level. Standardized PE radiography, in particular, was superior to CT tomography in the first molar region. This suggests that standardized PE radiographs should be utilized as a reliable modality for longitudinal and linear distance measurement, depending on implant length at local implantation site. PMID- 17344619 TI - Morphohistological change and expression of HSP70, osteopontin and osteocalcin mRNAs in rat dental pulp cells with orthodontic tooth movement. AB - Morphological change and expression of osteopontin, osteocalcin, and HSP70 mRNAs in rat dental pulp cells with experimental orthodontic tooth movement were investigated. Elastic rubber blocks, 0.65 mm in thickness, were inserted between the maxillary first and second molars in rats. In addition to morphological observations of HE staining and TUNEL staining at days 3, 7, 14 and 28 after insertion of elastic rubber blocks, expression of HSP70, osteopontin and osteocalcin mRNAs was also analyzed using quantitative RT-PCR with a LightCycler. Morphologically, proliferation and vasodilation of capillaries was evident in the pulp at days 3 and 7, and a sparse odontoblast layer and apoptosis in the pulp were observed at days 7 and 14 after rubber block insertion. Expression of HSP70, osteopontin and osteocalcin mRNAs in the experimental groups was higher than that in the control group at all time points. This suggests that orthodontic tooth movement causes degenerative changes and apoptosis in pulp cells, while pulp homeostasis is maintained at the genetic level. PMID- 17344620 TI - Detection of tumor DNA in plasma using whole genome amplification. AB - Altered microsatellite DNA in the blood of cancer patients may provide a novel means for tumor detection. Such alterations are a major characteristic of many types of tumor especially those associated with head or neck cancer. Moreover, recent evidence suggests that senescent tumor cells release DNA into the circulation, which is subsequently carried by the blood and thus enriched in the serum and plasma. We tested 10 head and neck cancer patients (5 with malignant melanomas (MM) and 5 with adenoid cystic carcinomas (ACC)) by polymerase chain reaction (PCR)-based microsatellite analysis of DNA from white blood cells and paired plasma samples. Our goal was to amplify two microsatellite markers, D1S243 and D19S246, which sometimes show microsatellite alterations in head and neck cancer patients. However amplification of fragments from three loci in the plasma samples proved impossible, probably due to the small amounts of DNA isolated. We used multiple displacement amplification (MDA) to amplify genomic DNA from the plasma samples. Two microsatellite fragments were amplified from whole genome amplified DNA. Among 5 heterozygote samples, 3 showed the same pattern in DNA samples from both blood cells and plasma but 2 showed loss of heterozygosity (LOH). Although further study is necessary to confirm whether the LOH found in this study reflects alteration in circulating tumor cell DNA, application of whole genome amplification may allow DNA analysis from limited amounts of such DNA and provide a minimally invasive diagnostic procedure and useful aid in therapy. PMID- 17344621 TI - Cone-beam CT (CB Throne) applied to dentomaxillofacial region. AB - Cone-beam CT (CBCT) systems specifically designed for hard-tissue imaging of the maxillofacial region have recently become commercially available. The newly developed CBCT system, CB Throne (Hitachi Medical Corp., Tokyo), is characterized by a number of features such as low dose, sub-millimeter spatial resolution, and a small footprint. This system has been clinically applied at Chiba Hospital, Tokyo Dental College, since April 2005. This article reports the characteristics of this system, and its diagnostic power for maxillofacial lesions and the pre operative planning dental implants. PMID- 17344622 TI - [Expert technologist and super technologist system: Aiming for the future radiological technologist (discussion)]. PMID- 17344624 TI - [Symposium. Determining the best methods of PET study from the technical point of view for the standardization of PET imaging protocols. 1. Influence on an image quality difference of transmission method]. PMID- 17344625 TI - [Symposium. Determining the best methods of PET study from the technical point of view for the standardization of PET imaging protocols. 2. Quantitative accuracy of three-dimensional PET acquisition]. PMID- 17344626 TI - [Symposium. Determining the best methods of PET study from the technical point of view for the standardization of PET imaging protocols. 3. PET acquisition conditions regarding specifications of a PET detector]. PMID- 17344627 TI - [Symposium. Determining the best methods of PET study from the technical point of view for the standardization of PET imaging protocols. 4. Examination of the optical acquisition time]. PMID- 17344628 TI - [Introduction and explanation of the JESRA X-0093(-2005): quality assurance (QA) guideline for medical imaging display systems]. PMID- 17344629 TI - [Overview and implementation of the revision of the law concerning the prevention of radiation hazard due to radioisotopes and others]. PMID- 17344631 TI - [Patent licensing (2)]. PMID- 17344630 TI - [Standards of X-ray examination for gastric mass survey]. PMID- 17344632 TI - [3D US imaging]. PMID- 17344633 TI - [Investigation of risk management for radiological technologists]. PMID- 17344634 TI - [Current status and problems concerning electronic storage and e-signature of official medical documents: Is electronic storage of the irradiation records possible?]. PMID- 17344635 TI - [Questions and answers for PET facilities: part 5]. PMID- 17344636 TI - [Development and evaluation of the medical imaging distribution system with dynamic web application and clustering technology]. AB - It has been noted that the downtime of medical informatics systems is often long. Many systems encounter downtimes of hours or even days, which can have a critical effect on daily operations. Such systems remain especially weak in the areas of database and medical imaging data. The scheme design shows the three-layer architecture of the system: application, database, and storage layers. The application layer uses the DICOM protocol (Digital Imaging and Communication in Medicine) and HTTP (Hyper Text Transport Protocol) with AJAX (Asynchronous JavaScript+XML). The database is designed to decentralize in parallel using cluster technology. Consequently, restoration of the database can be done not only with ease but also with improved retrieval speed. In the storage layer, a network RAID (Redundant Array of Independent Disks) system, it is possible to construct exabyte-scale parallel file systems that exploit storage spread. Development and evaluation of the test-bed has been successful in medical information data backup and recovery in a network environment. This paper presents a schematic design of the new medical informatics system that can be accommodated from a recovery and the dynamic Web application for medical imaging distribution using AJAX. PMID- 17344637 TI - [Influence of different movement systems on image quality: comparison of the sliding gantry CT system and the sliding table CT system]. AB - The combination of angiography and CT angiography (CTA) is increasingly being used for the diagnosis and treatment of hepatic cancer. Recently, a CT system with sliding gantry was developed to optimize patient safety and to shorten transfer time between the angiography and CTA tables. As the CT gantry itself undergoes considerable movement in sliding over the patient table, it was considered necessary to evaluate this system regarding the precision of movement and any possible effect on image quality. Therefore, in this preliminary study, we compared image quality between the sliding gantry CT (SGCT) system and the sliding table CT (STCT) system. Comparative analysis revealed that there was no significant difference in image noise, low contrast resolution, modulation transfer function (MTF) , or precision in gantry or table movement. It was also noted that although the effective slice thickness for the SGCT system was 1-4% thinner than the STCT system it had no influence on image quality. It was thus concluded that the sliding movement of the gantry does not influence the quality of images obtained with this CT system. PMID- 17344638 TI - [Examination of imaging parameter influence on image distortion in EPI]. AB - Echo planar imaging (EPI) is highly sensitive to static magnetic field inhomogeneities. The degree of local image compression and stretching is a function of the static field gradient in the phase-encoding direction. This is caused by the accumulation of a phase shift. Any static field shift will lead to a position shift in the image, and it is the regions with large static fields that are the most difficult to correct. We reduce image distortion by SENSE with an array coil. However, we often use a surface coil because we cannot use an array coil in clinical studies. In this case, image distortion becomes greater, and reduction of distortion is very important. For the purpose of this study, we examined the relation between imaging parameters and image distortion. Image distortion of EPI is unrelated to the following parameters: number of phase encodings, half scan, echo time, and diffusion b-value. However, the following parameters influenced image distortion: FOV, number of frequency encodings, rectangle FOV, and multi-shot imaging. Image distortion of EPI is decided by the area of the phase-encoding gradient and the interval of readout gradients. We hope that many institutions will find these data useful. PMID- 17344639 TI - [Survey of the current state of order-entry systems in the nuclear medicine field]. AB - BACKGROUND AND OBJECTIVES: In the "Grand Design for Computerization of the Medical Field" of December, 2001, the Ministry of Health, Labour and Welfare set a numerical target for the adoption of electronic medical charts nationwide in at least 60% hospitals with 400 or more beds. Therefore, the introduction and operation of an order-entry system, which is necessary for establishing electronic medical charts, became essential for each of these medical facilities. We surveyed the current state of order-entry systems for nuclear medicine, which are considered difficult to introduce owing to the particulars of their operation, and herewith report the results. METHODS: Questionnaires with a request for cooperation were sent by mail to 119 facilities nationwide that are engaged in nuclear medicine. The questionnaire surveyed 21 items, including operational status and restrictions of the order-entry system. RESULTS: The absolutely essential restriction settings for the introduction and operation of an order-entry system were not being used, and the scheduling of tests was being conducted on the basis of human judgment. CONCLUSION: The development of an order entry system that includes standardization of basic specifications (restrictions) according to the content and work are necessary for nuclear scans, for which the introduction and operation of an order-entry system can cause concern owing to the particulars of operation in the field of radiation. PMID- 17344640 TI - [Medical imaging: its medical economics and recent situation in Japan.]. AB - Two fields of radiology, medical imaging and radiation therapy, are coded separately in medical fee system, and the health care statistics of 2003 shows that expenditure on the former was 5.2% of the whole medical cost and the latter 0.28%. Introduction of DPC, an abbreviation of Diagnostic Procedure Combination, was carried out in 2003, which was an essential reform of medical fee payment system that have been managed on fee-for-service base throughout, and 22% of beds for acute patients care are under the control of DPC payment in 2006. As medical imaging procedures are basically classified in inclusive payment in DPC system, their accurate statistics cannot be figured out because of the lack of description of individual procedures in DPC bills. Policy-making of medical economics will suffer a great loss from the deficiency of detailed data in published statistics. Important role in clinical diagnoses of CT and MR results an increase of fee paid for them up to more than half of total expenditure on medical imaging. So, dominant reduction of examination fee has been done for MR imaging, especially in 2002, to reduce the total cost of medical imaging. Follows could be featured as major topics of medical imaging in health insurance system, (a) fee is newly assigned for electronic handling of CT-and-MR images, and nuclear medicine, and (b) there is still a mismatch between actual payment and quality of medical facilities. As matters related to medical imaging, the followings should be stressed; (a) numbers of CT and MR units per population are dominantly high among OECD countries, but, those controlled by qualified radiologists are at the average level of those countries, (b) there is a big difference of MR examination quality among medical facilities, and (c) 76% of newly-installed high-end MR units are supplied by foreign industries. Hopefully, there will be an increase in the concern to medical fee payment system and health care cost because they possibly influence patient care, personnel affairs in clinical facilities, technological development of medical devices, and so on. PMID- 17344641 TI - [Impact of optimization algorithms on the intensity map in IMRT treatment planning.]. AB - In inverse planning of IMRT, optimum intensity maps are generated using an optimization algorithm. In this paper, impacts of two different optimization algorithms on the intensity map in IMRT treatment planning were evaluated. These were from the steepest descent (SD) and simulated annealing (SA) methods. The following five patterns were compared: [1] SD with calculation time of 5 min; [2] SD with the terminal criterion based on cost function; [3] SA with calculation time of 5 min; [4] SA with the terminal criterion; and [5] SA with the terminal criterion using a smoothing filter. Differences of D(95%) for the planning target volume, V(70Gy) for the rectum wall and the bladder wall were up to 0.5, 1.8 and 3.2 %, respectively in all patterns. The dosimetric impact was negligible. In contrast, generated intensity maps were sensitive to the algorithms. Intensity maps generated by SA tended to have much fluctuation due to numerical artifacts compared to those generated by SD. The difference in the profile was over 7 % between the algorithms. The smoothing filter decreased the fluctuation in intensity maps of SA. In conclusion, it is important to understand impacts of optimization algorithms on the intensity map and the dose distribution. PMID- 17344642 TI - Performance of model observers for lesion detection in SPECT imaging. AB - We investigated the performance of model observers (the channelized Hotelling observer (CHO), channelized non-prewhitening observer (CNPWO) and non prewhitening observer (NPWO)) for lesion detection in single photon emission computed tomography (SPECT) imaging. METHODS: Using a simulation tool, we generated the numerical phantom with a hot lesion for cases having various contrasts and sizes and projection data including photon attenuation, scatter and distance-dependent collimator-detector response. The SPECT images were reconstructed using the filtered back-projection method and the ordered-subsets expectation-maximization method. Fifty lesion-absent and lesion-present images were generated and the detectability indices derived from CHO (d(CHO)), CNPWO (d(CNPWO)) and NPWO (d(NPWO)) were calculated from a total of 100 images. These procedures were repeated 5 times for each condition. The relationships among these detectability indices were investigated for various projection counts, lesion contrasts and lesion sizes. RESULTS: All detectability indices increased with increases of projection count, lesion contrast and lesion size. Although there were good correlations among them, the relationships between d(CHO) and d(NPWO) and between d(CNPWO) and d(NPWO) were not linear. The coefficient of variation of d(CHO) tended to be significantly greater than that of d(CNPWO) and d(NPWO). CONCLUSION: This study will be useful for understanding the performance of model observers when evaluating lesion detection in SPECT imaging. PMID- 17344643 TI - An inter-crystal scatter correction method for DOI PET image reconstruction. AB - New PET scanners utilize depth-of-interaction (DOI) information to improve image resolution, particularly at the edge of field-of-view while maintaining high detector sensitivity. However, the inter-crystal scatter (ICS) effect cannot be neglected in DOI scanners due to the use of smaller crystals. ICS is the phenomenon wherein there are multiple scintillations for irradiation of a gamma photon due to Compton scatter in detecting crystals. In the case of ICS, only one scintillation position is approximated for detectors with Anger-type logic calculation. This causes an error in position detection and ICS worsens the image contrast, particularly for smaller hotspots. In this study, we propose to model an ICS probability by using a Monte Carlo simulator. The probability is given as a statistical relationship between the gamma photon first interaction crystal pair and the detected crystal pair. It is then used to improve the system matrix of a statistical image reconstruction algorithm, such as ML-EM in order to correct for the position error caused by ICS. We apply the proposed method to simulated data of the jPET-D4, which is a four-layer DOI PET being developed at the National Institute of Radiological Sciences. Our computer simulations show that image contrast is recovered successfully by the proposed method. PMID- 17344644 TI - Design and inital evaluation of a 4-layer DOI-PET system: the jPET-D4. AB - PET scanners are an important component in functional brain imaging devices. Several PET scanners have been developed during the last two decades for brain research studies. We are developing a high-performance brain PET scanner, jPET D4. This scanner is designed to achieve not only high spatial resolution but also high sensitivity using four-layered depth-of-interaction (DOI) detectors. The scanner has five block detector rings with the ring diameter of 390 mm and each block detector ring consists of 24 DOI detectors. In previous work, we have demonstrated that 3 mm FWHM uniform spatial resolution within the field-of-view could be realized. In this paper, we describe the jPET-D4 system and evaluate its performance. The average energy resolution for 120 DOI detectors is optimized to 16 % +/- 1.0 %. The scatter fraction for this system is 40 % with an energy window of 400-600 keV. The sensitivity for the point source is 102 kcps/MBq (10.2 %) with a 400 keV LLD. Maximum noise equivalent count rate (NECR) is 154 kcps at 11 kBq/ml with a 10 ns coincidence time window. We evaluated scatter fraction and NECR following procedures based on NEMA NU2-1994. These first evaluation measurements indicate the jPET-D4 has good performance. PMID- 17344645 TI - SREBP-1c transcription factor and lipid homeostasis: clinical perspective. AB - Insulin has long-term effects on glucose and lipid metabolism through its control on the expression of specific genes. In insulin sensitive tissues and particularly in the liver, the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) transduces the insulin signal. SREBP-1c is a transcription factor which is synthetized as a precursor in the membranes of the endoplasmic reticulum and which requires post-translational modification to yield its transcriptionally active nuclear form. Insulin activates the transcription and the proteolytic maturation of SREBP-1c. SREBP-1c induces the expression of a family of genes involved in glucose utilization and fatty acid synthesis and can be considered as a thrifty gene. Since a high lipid availability is deleterious for insulin sensitivity and secretion, a role for SREBP-1c in dyslipidaemia and type 2 diabetes has been considered in genetic studies and some association demonstrated. Finally, SREBP-1c could also participate to the hepatic steatosis observed in humans and related to alcohol consumption and hyperhomocysteinaemia, two pathologies which are concomitant with a stress of the endoplasmic reticulum and an insulin-independent SREBP-1c activation. PMID- 17344646 TI - Quantitative ultrasound assessment of bone health in the neonate. AB - For a number of reasons there is a need to explore reliable non-invasive methods for assessing bone health in neonates and young infants. Epidemiological studies suggest that early events in life may predispose the adult to degenerative diseases such as osteoporosis. Preterm infants have an increased risk of low bone mass because of limited bone mass accretion in utero and a greater need for bone nutrients. Despite improvements in neonatal care fractures still occur. The diagnosis of osteopaenia of prematurity remains difficult as there is no screening test which is both sensitive and specific. Biochemical indices are non diagnostic, and plain X-rays in the absence of fractures are poor at diagnosing bone disease. Although dual energy X-ray absorptiometry is increasingly used to assess bone mineral status in newborn infants, the size and immobility of the scanner, the length of time to perform the scan and use of ionising radiation make it unsuitable for routine use in the setting of the fragile very low birth weight infant. Quantitative ultrasound (QUS) was first developed in 1984, as a non-ionising, portable and low cost method of assessing bone health. The measurements obtained from QUS are thought to be related not only to the mineral density of the bone but also to reflect parameters of bone quality and strength. Preliminary studies suggest that this technique may be a useful method of assessing changes in bone health in preterm infants, but the data need to be interpreted carefully. This review will concentrate on the methodology of QUS and the studies that have already been performed in neonates. PMID- 17344647 TI - Glucocorticoid receptor expression in the cortex of the neonatal rat brain with and without focal cerebral ischemia. AB - BACKGROUND/AIMS: Glucocorticoid receptors (GR) mediate cellular processes which may be neuroprotective and/or neurotoxic to the neonatal rat brain. Our aim was to describe GR ontogeny in the developing rat brain cortex and changes in GR expression after permanent neonatal focal cerebral ischemia (FCI). METHODS: GR Western blots and immunohistochemical stains were performed on neonatal rat cortices on P1, P3, P7, P10, P15, and P30 and on P7 at 1 h, 3 h, 6 h, 12 h, 24 h, and 72 h after FCI or sham-operation (S-O), 8 per group. Nissl staining was performed on FCI or S-O P7 cortical samples. RESULTS: Cortical GR expression was increased by 65.2% at P7, 110.1% at P15, and 87.0% at P30, compared to P1. On P7, GR expression decreased in the ischemic cortex after 6 h and in the non-ischemic cortex after 24 h of FCI (p < 0.05). Cortical GR expression was not altered in S O P7 rats. Immunohistochemistry supported Western blot findings. Nissl staining revealed no gross decrease in neuronal number in non-ischemic cortices after 24 h of FCI, compared to baseline. CONCLUSIONS: Neonatal rat cortical GR expression increases during P1 to P30, peaking at P15. At P7, cortical GR expression appears downregulated in the ischemic cortex after 6 h and in the non-ischemic cortex after 24 h of FCI. Thus, cortical GR may play important roles in normal brain development and neonatal brain injury responses. PMID- 17344648 TI - Effects of severe hypocapnia on expression of bax and bcl-2 proteins, DNA fragmentation, and membrane peroxidation products in cerebral cortical mitochondria of newborn piglets. AB - BACKGROUND: Hypocapnia occurs in the newborn infant inadvertently or as a therapeutic modality and may result in neuronal and mitochondrial alterations in the newborn brain. Since mitochondria regulate apoptosis, these alterations may initiate a cascade of reactions that lead to apoptotic cell death. OBJECTIVES: This study tests the hypothesis that hypocapnia results in increased expression of the pro-apoptotic protein Bax, fragmentation of DNA and membrane lipid peroxidation in cerebral cortical mitochondria (mt) of newborn piglets. METHODS: Studies were performed in three groups of anesthetized normoxic newborn piglets: hypocapnic (H, n = 5), ventilated at a PaCO(2) of 11-15 mm Hg; normocapnic (N, n = 5), ventilated at a PaCO(2) of 40 mm Hg; and corrected normocapnic (CN, n = 4), ventilated as H with CO(2) added to maintain normocapnia. Tissue ATP and phosphocreatine levels were determined. Mitochondrial membrane proteins were separated, transblotted and probed with antibodies to Bax and Bcl-2. Bands were detected by enhanced chemiluminescence and analyzed by imaging densitometry. mtDNA was isolated. Cell and mitochondrial membrane lipid peroxidation products were measured spectrofluorometrically. RESULTS: ATP and PCr concentrations were similar in the 3 groups. The ratio of Bax/Bcl-2 increased significantly in H compared to N and CN. mtDNA fragmentation was also significantly greater in H compared to N or CN. Membrane lipid peroxidation was higher in H than in N or CN; and in CN compared to N. CONCLUSIONS: The data demonstrate that severe hypocapnia results in increased Bax expression, DNA fragmentation, and membrane lipid peroxidation in mitochondria of cerebral cortical neurons of newborn piglets, and may result in apoptotic cell death. PMID- 17344649 TI - Growth and development in a heliox incubator environment: a long-term safety study. AB - BACKGROUND: Neonates exposed to mechanical ventilation may develop bronchopulmonary dysplasia (BPD). BPD neonates exhibit a 25-30% increase in energy expenditure which may decrease the rate of growth and development. Heliox has been shown to improve pulmonary function and may decrease energy expenditure. We hypothesized that heliox would provide a safe environment for sustained growth and development. OBJECTIVE: To assess the safety of the heliox environment we observed developmental milestones; recorded changes in weight, total length, limb length and head circumference; measured blood chemistries; compared primary organ and muscle weights, and analyzed muscle enzymatic activity. DESIGN/METHODS: Four day-old rabbit pups (n = 27) were randomized into control (21% O(2); 79% N(2)) or heliox (21% O(2); 79% He) groups, then raised for 14 days at 26.7 degrees C and 50% relative humidity. Pups were euthanized on day 14, blood drawn and primary organs, diaphragm and gastrocnemius weighed and snap-frozen. RESULTS: All pups thrived in both environments, achieving expected developmental milestones. There were no physiologically significant group differences in weight, growth factors, tissue weight, blood chemistry or muscle enzyme activity. CONCLUSIONS: No observed long-term differences in growth or development. RESULTS demonstrated that long-term heliox exposure is safe in this rabbit model. These data suggest that heliox administration may provide time for pulmonary improvement in the BPD population, warranting appropriate clinical trials. PMID- 17344650 TI - Safety of high-dose recombinant erythropoietin in a neonatal rat model. AB - BACKGROUND: High-dose recombinant erythropoietin (rEpo) is neuroprotective in neonatal animal models of brain injury, but the long-term consequences of neonatal exposure have not been studied. OBJECTIVES: We hypothesized that multiple injections of high-dose rEpo during the neonatal period would be safe, and would improve neurologic outcomes after exposure to neonatal hypoxia or hypoxic-ischemic injury. METHODS: Three experimental groups of Sprague-Dawley rats were assessed: (1) normoxia, (2) hypoxia and (3) hypoxia-ischemia. Groups 1 and 2 were given 0, 2,500 or 5,000 U/kg rEpo subcutaneously for the first 5 days of life (P1-P5). Group 2 animals also underwent 2 h of hypoxia (8% O(2)) daily from P1-P3. Group 3 animals underwent right carotid artery ligation followed by hypoxia (8% O(2) x 90 min) on P7, followed by either vehicle or rEpo (2,500 U/kg subcutaneously QD x3). We evaluated short- and long-term physiologic and behavioral outcomes. Major organs were evaluated grossly and histologically. RESULTS: rEpo treatment transiently raised hematocrit, prevented hypoxia-induced delays in geotaxis and growth, improved forelimb strength, promoted liver growth in males, lowered the adult platelet count, but did not alter other CBC indices or histology. rEpo prevented hypoxia-ischemia-induced learning impairment and substantia nigra neuron loss. CONCLUSIONS: Repeated treatment of newborn rats with high-dose rEpo was safe under all conditions tested. rEpo treatment improved the development of hypoxia-exposed newborns and prevented the learning impairment and dopamine neuron loss due to unilateral hypoxic-ischemic brain injury. PMID- 17344651 TI - Age-related changes in pro-inflammatory cytokines, acute phase proteins and cortisol concentrations in neonatal piglets. AB - Age-related changes have been described in the resting levels of cortisol and acute phase proteins in the neonatal pig. This study evaluated the plasma concentrations of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), the acute phase proteins C-reactive protein (CRP), serum amyloid A (SAA) and haptoglobin (Hp), as well as cortisol during the first week of postnatal life in piglets. The influence of invasive managerial practices such as teeth clipping, ear notching and tail docking on possible age-related changes in the production of these inflammatory mediators was also assessed. A total of 96 piglets were selected from 24 litters at birth, and were randomly assigned to one of four sampling times over the first week of life and one of two treatments. Blood samples were taken at 1, 3, 5 or 7 days of age. Piglets were ear notched, teeth clipped and tail docked (NCD), or were left untreated (CON). Significant effects of age were found in plasma concentrations of TNF-alpha, SAA, Hp and cortisol (p < 0.001). Concentrations of TNF-alpha and Hp increased with age, and peak concentrations were found on day 5. SAA and cortisol levels were highest on day 1, decreasing gradually with age. NCD piglets tended to have higher levels of plasma Hp than CON animals (p = 0.066). However, no differences between NCD and CON piglets were found in any other parameter measured. Furthermore, age effects were not affected by these husbandry practices. These results indicate that age-related changes exist in several inflammatory mediators, and suggest that these managerial practices do not result in systemic inflammation in early postnatal life of piglets. PMID- 17344652 TI - Glucagon-like peptide-2 in umbilical cord blood from mature infants. AB - BACKGROUND: Glucagon-like peptide-2 (GLP-2) seems to be a highly specific intestinotrophic mediator. From animal studies, GLP-2 is known to increase in the early neonatal period before it falls to adult level. No studies in newborn infants addressing this specific subject have been published so far. OBJECTIVES: To measure GLP-2 concentrations in umbilical cord blood from healthy mature infants and to assess any influence from the processes associated with spontaneous birth to GLP-2 production. SUBJECTS: Twenty-one children delivered by elective cesarean section for maternal reasons and 18 children delivered spontaneously vaginally and without complications were included. Gestational age (GA) was median (range) 38.7 (40.7-37.1) weeks and 40.2 (41.9-38) weeks, and birth weight was median (range) 3,210 (4,820-2,100) g and 3,396 (4,225-3,050) g, respectively. The infants had no diagnosed diseases or malformations. METHODS: Umbilical cord blood was collected shortly after birth. Plasma was separated and GLP-2 immunoreactivity was measured with a specific NH(2)-terminal radioimmunoassay. RESULTS: GLP-2 was detected in all samples. Mean values +/-SD were 16.7 +/- 3.9 pmol/l and range was 32-11 pmol/l, which is comparable to adult fasting levels. No significant correlation to birth weight (p = 0.087) or to cesarean section (p = 0.059) was found. In multiple linear regression analysis (GLP-2 vs. GA + cesarean section), neither vaginal delivery nor GA were statistically significantly related to the level of GLP-2 (p = 0.28 and 0.18), respectively. CONCLUSIONS: GLP-2 is present in human cord blood by the time of birth. The level of GLP-2 is comparable to adult fasting levels. Spontaneous birth at most induces a minor increase in GLP-2 in term infants. In the narrow age interval studied, no significant effect of maturation was seen. PMID- 17344653 TI - Immunomodulatory effect of vitamin C on intracytoplasmic cytokine production in neonatal cord blood cells. AB - BACKGROUND: Vitamin C (ascorbic acid) is an essential water-soluble antioxidant in cells and plasma. Besides metabolic functions, vitamin C is also known to contribute to immune homeostasis. Recently, it has been demonstrated that vitamin C has an inhibitory effect on the expression of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in adult whole blood cells in vitro. It has been postulated that vitamin C might be an interesting compound for modulation of an over-exuberant immune response, e.g., in patient cohorts susceptible for the development of systemic inflammatory response syndrome such as neonates. It was the aim of this study to investigate the modulatory effects of vitamin C on the production of inflammatory mediators in neonatal cord blood cells. METHODS: The intracytoplasmic production of pro inflammatory cytokines in neonatal cord blood cells stimulated with lipopolysaccharide or phorbol 12-myristate 13-acetate/ionomycin was assessed by flow-cytometry. RESULTS: In contrast to our previous observations from adult whole blood cells, 20 mM vitamin C mildly stimulated the percentage of neonatal monocytes producing IL-6 after lipopolysaccharide stimulation (e.g., 11.3% increase compared to control, p = 0.005). In the presence of 20 mM vitamin C, even a stronger stimulatory effect was noted for the percentage of IL-8 (e.g., 46.7% increase, p < 0.001) and TNF-alpha producing neonatal monocytes (e.g., 69.2% increase, p = 0.004; n = 20). In accordance with adult data, the percentage of neonatal lymphocytes producing IL-2 after phorbol 12-myristate 13 acetate/ionomycin stimulation was dose-dependently reduced (e.g., 41.3% inhibition, p = 0.001, 20 mM vitamin C), while the percentage of TNF-alpha producing lymphocytes was mildly stimulated (e.g., 20.8% increase, p = 0.003, 20 mM vitamin C). CONCLUSIONS: Interestingly, vitamin C was demonstrated to enhance pro-inflammatory responses in CD14(+) cord blood cells while only intracellular IL-2 production in CD3(+) cells was diminished. These data suggest that vitamin C differentially influences intracytoplasmic cytokine production in adults and neonates, and further studies are needed to elucidate the underlying mechanisms of this selective immunomodulation. PMID- 17344654 TI - Hemoglobin switch in the newborn: a flow cytometry analysis. AB - BACKGROUND: Hemoglobin (Hb) production switches upon birth from fetal Hb (HbF) to adult Hbs. HbF production is reactivated in sickle cell anemia and beta thalassemia, where increased HbF ameliorates clinical symptoms and HbF stimulating drugs are used for treatment. Understanding of the switch is therefore of basic interest and important for rational drug design. We studied the switch by determining changes after birth in the frequency and HbF-content of HbF-containing red blood cells (F-RBC) and reticulocytes (F-retics). METHODS: Blood samples of neonatal cord, babies in their first year and adults were stained with both phycoerythrin-conjugated anti-human HbF antibodies and the nucleic acid dye thiazol-orange, and analyzed by flow-cytometry. RBC and retics were distinguished by their different thiazol orange-derived fluorescence and their HbF content was determined by the intensity of phycoerythrin-derived fluorescence. RESULTS: The frequency of both F-RBC and F-retics decreases with time after birth. In most cases, the percentage of F-RBC was higher, but their HbF-content was lower than that of retics. The HbF content of the F-RBC and the F retics showed a gradual decrease with age. CONCLUSIONS: The results can be explained by two models: (A) A pool of homogenous stem cells that undergo gradual changes in their globin transcription pattern. (B) A pool of heterogeneous stem cells with varying HbF potentials that become active in an age-dependent manner: first, cells with a high HbF potential and then cells with a gradually lower HbF potential. In both models, these changes are induced by a biological clock and environmental factors. PMID- 17344655 TI - Oropharyngeal tumor in the newborn: a case report. AB - BACKGROUND: An oropharyngeal tumor presenting as a protruding mass from the mouth of the newborn infant is very rare. This mass has the potential to obstruct the airway and requires urgent medical management, diagnosis and appropriate surgical management. OBJECTIVES: To report a case of a newborn with an oropharyngeal mass presenting at birth and focus on key clinical issues for the physician faced with the care of such an infant. METHODS AND RESULTS: We describe a newborn infant who was born with a large mass protruding from the oral cavity at birth, without respiratory distress. The mass was surgically removed with no complications. The histology of the mass revealed it to be a pharyngeal dermoid polyp, also called 'hairy polyp'. The infant did well after tumor removal and was discharged home within a couple of days. CONCLUSIONS: We report a case of a newborn with a pharyngeal dermoid polyp presenting as an oropharyngeal mass. PMID- 17344656 TI - Neonatal ventilation with inhaled nitric oxide vs. ventilatory support without inhaled nitric oxide for infants with severe respiratory failure born at or near term: the INNOVO multicentre randomised controlled trial. AB - BACKGROUND: Evidence from European centres to support the use of nitric oxide (NO) in mature newborns with evidence of severe respiratory failure is sparse. METHODS: Infants of >33 weeks' gestation, <28 days old, and with severe respiratory failure requiring ventilatory support were randomised to receive or not to receive inhaled NO (iNO). The study was not blinded. RESULTS: Sixty infants were recruited (29 allocated iNO, 31 no iNO) from 15 neonatal units in the UK, Finland, Belgium and the Republic of Ireland. 15/60 recruited babies died, and 8.1% of the survivors (4/45) were classified as severely disabled at 1 year. There was no statistically significant difference between the randomised groups in terms of the primary outcome of death or severe disability by the corrected age of 1 year (relative risk = 0.96 (95% confidence interval = 0.46 2.03); p = 0.86) (Fisher's exact p = 1.00). The costs of NO were outweighed by reduced extra corporeal membrane oxygenation costs in the iNO group. The mean total hospitalisation costs were lower in the iNO group, although the mean difference (1,697 pounds) was not statistically significant (95% confidence interval = -14,472 to 11,478). CONCLUSIONS: The results complement those of previous studies that suggest NO is cost-effective and reduces the need for extra corporeal membrane oxygenation in this group of babies. Overall survival rates compare unfavourably with results of US trials. PMID- 17344657 TI - Prolonged dynamic changes in autonomic heart rate modulation induced by acid laryngeal stimulation in non-sedated lambs. AB - BACKGROUND: Exaggerated laryngeal chemoreflexes (LCR) have been implicated in the occurrence and prolongation of apnea in premature and term neonates. OBJECTIVES: To test the hypothesis that the cardiovascular component of the LCR can occur and be prolonged in the absence of apnea. METHODS: Bolus injections of 0.5 ml of citric acid (CitAc) and serum saline were administered onto the larynx in seven non-sedated lambs, aged 4-5 days, during quiet sleep. Blood pressure (BP) and heart rate (HR) variability measurements were taken and compared with results obtained prior to stimulation and with saline. RESULTS: Apneas were rare and occurred consistently in the 32-beat period (10 s) following stimulation. The increase in BP and decrease in HR were consistent after CitAc and saline. All the studied components of HR variability significantly increased after CitAc, but not after saline. The low frequency estimates were significantly increased during a 480-beat period (133 +/- 6.6 s) following CitAc stimulation. Analysis of gains and respiration showed that bradycardia and HR variability changes were neither related to an apnea nor a vagal arterial baroreflex. CONCLUSION: This long lasting increase in HR variability indicates a prolonged disturbance of the cardiovascular regulatory systems, consisting in increased sympathetic and parasympathetic tones following CitAc stimulation. PMID- 17344658 TI - Cardiovascular effects of sildenafil in neonates and infants with congenital diaphragmatic hernia and pulmonary hypertension. AB - BACKGROUND: Pulmonary hypertension is a common problem in patients with congenital diaphragmatic hernia (CDH). In a subset of these patients, pulmonary hypertension persists despite optimized ventilatory management and supportive care. Sildenafil, a phosphodiestrase V inhibitor, has been used in the treatment of pulmonary hypertension in adults and children. Cardiovascular effects of sildenafil in patients with CDH and pulmonary hypertension are not known. OBJECTIVE: To describe the changes in cardiovascular and respiratory parameters in newborn infants with CDH and persistent pulmonary hypertension refractory to inhaled nitric oxide (iNO) during the first 2 weeks of sildenafil administration. METHODS: Retrospective data analysis of seven patients with CDH (birth weight = 2,573 +/- 1,019 g; gestational age = 35.6 +/- 4.3 weeks) receiving oral sildenafil for pulmonary hypertension refractory to iNO. Findings of serial echocardiograms and data on cardiovascular and respiratory status were assessed. RESULTS: Right cardiac output increased and left cardiac output tended to increase 1.5-4 h after initiation of sildenafil and the increase was sustained throughout the study. Echocardiographic indices of pulmonary hypertension showed an apparent reduction in abnormally high pulmonary vascular resistance. Systemic blood pressure tended to decrease. Shortening fraction did not change. Ventilatory index and the need for iNO tended to decrease in the five surviving infants. CONCLUSIONS: These preliminary findings suggest that sildenafil may improve cardiac output by reducing pulmonary hypertension refractory to iNO in patients with CDH. PMID- 17344659 TI - The relationship between birth weight leptin and bone mineral status in newborn infants. AB - BACKGROUND: The positive relationship between fat mass, bone mass and leptin has been shown in fetal mouse cartilage/bone. It has been shown that umbilical venous leptin predicts both the size of the neonatal skeleton and its estimated volumetric mineral density. AIMS: This study investigates how birth weight and bone mineralization correlate with leptin levels. In addition, we aimed to determine the predictive value of anthropometrics measurements and gender on variability in bone mineral status. METHODS: Umbilical cord venous blood samples were obtained at the delivery from 100 term newborn infants. Forty of the newborn infants had birth weights appropriate for gestational age (AGA), 30 were small for gestational age (SGA) and 30 were large for gestational age (LGA). Data were acquired using the whole body dual energy X-ray obsorptiometry scanner in the first 24 h after birth. RESULTS: Leptin concentrations were higher in LGA (36.6 +/-12.0 ng/ml; p < 0.0001), but lower in SGA (11.7 +/- 5.6 ng/ml; p < 0.001) than in AGA infants (20.3 +/- 7.6 ng/ml). Whole body bone mineral density and whole body bone mineral content were higher in LGA babies (0.442 +/- 0.025 g/cm(2), 71.6 +/- 9.0 g, p < 0.01, p < 0.001, respectively) but lower in SGA (0.381 +/- 0.027 g/cm(2), 29.1 +/- 9.1 g, p < 0.001, p < 0.001, respectively) than in AGA babies (0.426 +/- 0.022 g/cm(2), 53.7 +/- 9.6 g, respectively). The percentage of whole body bone mineral content was lower in SGA (1.3 +/- 0.3) than in AGA (1.6 +/- 0.2, p < 0.001) and LGA (1.7 +/- 0.2, p < 0.001). In stepwise linear regression analyses models; leptin is not found related to the bone indices. CONCLUSION: Our study does not provide support for the hypothesis that leptin may play a major role in the regulation of bone metabolism in the developing skeleton. PMID- 17344660 TI - Interleukin-8 and monocyte chemotactic protein-1 mRNA expression in perinatally infected and asphyxiated preterm neonates. AB - BACKGROUND: Inflammation due to perinatal infection (PI) and perinatal asphyxia (PA) may cause damage to various tissues and very often to the immature brain of the fetus and the newborn. Previously, we have shown that the neonatal immune system has the ability to produce increased chemokine protein levels in the serum during the inflammatory response caused by PI and PA. AIM: The aim of our present study was to investigate mRNA levels of the proinflammatory chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in peripheral blood leukocytes from infected and asphyxiated neonates. METHODS: Forty-two premature neonates were studied; 11 with PI, 16 with PA and 15 without PA and PI, were used as controls. IL-8 and MCP-1 mRNA levels were investigated in whole blood and in phytohemagglutinin-activated lymphocytes using semi-quantitative polymerase chain reaction and real-time polymerase chain reaction, respectively. RESULTS: IL-8 mRNA levels were significantly increased in whole blood both during PA and PI, while MCP-1 mRNA levels were not. In vitro activated lymphocytes expressed significantly increased IL-8 mRNA levels during PI, whereas no increase was observed during PA. MCP-1 mRNA levels were significantly increased in activated lymphocytes during PA, while no increase was observed during PI. CONCLUSIONS: Our data show that chemokine mRNA levels expressed by activated lymphocytes during inflammation caused by PIs are different to those expressed during PAs. These findings might have important implications during the administration of specific chemokine antagonists in order to prevent or reduce tissue damage caused by inflammation. PMID- 17344661 TI - The potential Salmonella aroA- vaccine strain is safe and effective in young BALB/c mice. AB - BACKGROUND: Due to the increased susceptibility of neonates to pathogens including those with mutations, the use of live vaccine strategies in the human population may present a potential risk to the young. OBJECTIVES: The specific aim of this study was to assess the risk that prospective Salmonella enterica serovar Typhimurium vaccine strains pose for the neonate and determine whether the strains are an effective vaccine by assessing the adaptive immune response. METHODS: To evaluate the susceptibility of young mice to potential vaccine strains, S. typhimuriumaroA(-) and Delta phoP mutant strains were labeled by chromosomal insertion of the lux operon--this serves as a readily traceable marker of infection using noninvasive imaging methods. BALB/c mice ages 1, 2, 4, and 6 weeks of age were fed the bioluminescent aroA(-) or Delta phoP strains and the course of infection was monitored by in vivobioluminescence imaging. In addition, blood samples were collected post-inoculation to assess the IgG response of mice to S. typhimurium LPS. RESULTS: Young BALB/c mice were not susceptible to the aroA(-) strain in contrast to their susceptibility to the Delta phoP strain at a dose of 10(9) colony forming units. Delivery by oral feeding of the aroA(-) and Delta phoP strains in young mice also produced a robust IgG anti-LPS response. CONCLUSION: Here, we report that young 2-week-old mice orally fed the bioluminescent aroA(-) S. typhimurium strain were not susceptible to infection and elicited a protective immune response. PMID- 17344662 TI - Blood galactose and glucose levels in mothers, cord blood, and 48-hour-old breast fed full-term infants. AB - BACKGROUND: Although galactose is an important component in human lactose, there are few reports of its role in the newborn metabolism. OBJECTIVE: To determine the relationship of blood galactose and glucose levels in mothers, cord blood, and breast-fed full-term newborn infants. METHODS: Maternal and cord vein blood samples were obtained from 27 pregnant women at delivery, and from their breast fed, full-term newborns 48 h later. Galactose and glucose were determined by HPLC. Statistical analysis used ANOVA and Pearson correlation with p < 0.05. RESULTS: Maternal galactose concentrations (0.08 +/- 0.03 mmol/l) were similar to cord blood galactose (0.07 +/- 0.03 mmol/l; p = 0.129). However, newborn blood galactose (0.05 +/- 0.02 mmol/l) was significantly lower than both cord (p = 0.042) and maternal blood (p = 0.002). Maternal blood glucose levels (4.72 +/- 0.86 mmol/l) were higher than cord blood (3.98 +/- 0.57 mmol/l; p < 0.001), and cord blood concentrations were higher than newborn blood levels (3.00 +/- 0.56 mmol/l; p < 0.001); all values expressed as mean +/- SD. Significant correlation was only seen between maternal and cord blood galactose levels (r = 0.67; p < 0.001) and glucose levels (r = 0.38; p = 0.047). CONCLUSION: The association and similarity between maternal and cord blood galactose levels suggest that the fetus is dependent on maternal galactose. In contrast, the lower galactose levels in newborn infants and a lack of association between both suggest self-regulation and a dependence on galactose ingestion. PMID- 17344663 TI - Perfluorocarbon suppresses lipopolysaccharide- and alpha-toxin-induced interleukin-8 release from alveolar epithelial cells. AB - BACKGROUND/AIMS: Human pulmonary alveolar epithelial (A549) cells release interleukin-8 (IL-8) on stimulation by lipopolysaccharide (LPS) and alpha-toxin. We hypothesised that the perfluorocarbons (PFCs), perflubron and FC-84, would block stimulation of A549 cells by these toxins. METHODS: The levels of IL-8 production in A549 cells were measured following exposure to toxins for 24 h with or without PFC. The amount of IL-8 released from A549 cells was measured by enzyme-linked immunosorbent assay, and the level of IL-8 mRNA was measured by real-time RT-PCR. RESULTS: When stimulated with LPS or alpha-toxin, IL-8 release from A549 cells increased. There were no significant differences in level of IL-8 release between cells pre-incubated for 24 h with or without PFC after toxin stimulation for 24 h. When PFC was administered along with LPS stimulation, the level of IL-8 release was decreased (LPS control, 1,398 +/- 110 pg/well; FC-84, 686 +/- 50 pg/well; perflubron, 749 +/- 137 pg/well; p < 0.05). Levels of IL-8 mRNA expression were significantly higher with than without LPS, and those with LPS and perflubron were significantly lower than those with LPS alone. CONCLUSIONS: The results show that PFCs block stimulation of A549 cells by LPS or alpha-toxin. PFC may be useful clinically in treatment of pulmonary inflammation in the alveolar space. PMID- 17344664 TI - Near-infrared spectroscopy as a screening tool for patent ductus arteriosus in extremely low birth weight infants. AB - BACKGROUND: Patent ductus arteriosus (PDA) is frequent and potentially pathologic in preterm infants. A simple bedside tool to screen for ductal patency would assist in the care of extremely low birth weight (ELBW) infants. OBJECTIVE: To investigate the utility of near-infrared spectroscopy (NIRS) in identifying ELBW infants who would benefit from early echocardiography. METHODS: Tissue oxygen saturation (S(t)O(2)) was measured by NIRS in the lungs, brain, skeletal muscle and kidney of 20 ELBW infants. Comparisons were made between the S(t)O(2) in these organs and the need for intervention for a PDA. All studies were performed within the first 4 days of life. Similar measurements were performed following treatment with indomethacin in nine of the patients. RESULTS: The S(t)O(2) of skeletal muscle (left deltoid) and kidney differed between the infants who were treated for PDA and those who were not (p = 0.01 for both). As a screen for a PDA requiring intervention, deltoid S(t)O(2) had sensitivity 77% and specificity 83%, and kidney S(t)O(2) had sensitivity 85% and specificity 83%. Following treatment with indomethacin, the low S(t)O(2) in the deltoid and kidney increased toward the range seen in patients who did not require treatment of a PDA. Inter- and intra-observer variability ranged from minimal to high. CONCLUSION: This pilot study of a portable NIRS device shows encouraging efficacy in identifying ELBW infants who were likely to benefit from early echocardiography and subsequent intervention to close a PDA. Further study is warranted. PMID- 17344665 TI - Tubular disorders in low birth weight neonates after prolonged antibiotic treatment. AB - BACKGROUND: Aminoglycosides (AGs) and vancomycin (VM) are potentially nephrotoxic antibiotics and their co-administration increases the incidence of nephrotoxicity in adult patients. Their combined effects on renal function in extremely low birth weight (ELBW) infants (<1,000 g) have not been previously reported. OBJECTIVES: Investigation of tubular disturbances in five ELBW neonates following repeated and prolonged treatment with a variety of AGs combined with VM. RESULTS: The drug levels were maintained in the neonatal therapeutic range. Renal tubular wasting of potassium, phosphate, and calcium, along with hypokalemia, was documented in all neonates studied while associated hypophosphatemia was observed in three of the five neonates and a transient rise in serum creatinine in four. The renal disturbances resolved completely 1-2 weeks after cessation of treatment. CONCLUSION: Renal tubular disturbances due to AG and VM treatment in ELBW neonates may be more common than they are diagnosed. Early detection and appropriate electrolyte supplementation may help to normalize serum electrolyte levels in these infants. PMID- 17344666 TI - Adherence to endocrine therapy for breast cancer. AB - PURPOSE: Despite the demonstrated efficacy of long-duration adjuvant tamoxifen and aromatase inhibitor use in breast cancer management, information on adherence to such therapy is limited. Therefore, we reviewed the published literature regarding hormonal therapy adherence in clinical trial and practice settings. METHODS: A systematic search of the PubMed database, augmented by a review of manuscript references and conference proceedings, commonly identified adherence reports in clinical trials but identified only 9 adherence reports in clinical practice settings. RESULTS: In adjuvant breast cancer clinical trials with longer (> or =4 years) follow-up, hormonal therapy (tamoxifen or aromatase inhibitors) was prematurely discontinued by about 23-28% of the study participants. Adherence to aromatase inhibitors did not differ from adherence to tamoxifen in this setting. In breast cancer prevention trials, tamoxifen was prematurely discontinued by 20-46% of the participants. In clinical practice settings, only 2 reports addressed longer-duration (>4 years) adherence to adjuvant tamoxifen use. In these, tamoxifen was prematurely discontinued by 30-50% of the patients. CONCLUSION: Adherence to prescribed breast cancer hormone therapy has not received concerted attention. Current, albeit limited, evidence suggests long term hormone therapy adherence may represent an area limiting optimal breast cancer patient treatment. PMID- 17344667 TI - The dual role of saliva in oral carcinogenesis. AB - Oral squamous cell carcinoma (OSCC), the most common head and neck malignancy, represents a serious public health problem. Exposure to cigarette smoke (CS)/tobacco is considered responsible for up to 90% of cases of this cancer worldwide. Free radicals, which often originate in CS and reactive nitrogen species, are frequently considered to be the reagents capable of triggering the process leading to malignant transformation. Initially dysplastic lesions of the mucosa are transformed into in situ carcinoma lesions, eventually resulting in a full-blown infiltrating and metastasizing OSCC. A synergistic, deleterious interaction between CS and saliva has been reported, which may result in the rapid destruction of biological macromolecules such as enzymes and proteins, giving it a possible pivotal role in the pathogenesis of OSCC. This lethal synergistic effect of CS and saliva is probably based on the reaction between redox-active metals in saliva and low reactive free radicals in CS. This is a novel concept recognizing that when exposed to CS, salivary behavior is reversed and saliva loses its antioxidant capacity, becoming a potent pro-oxidant milieu. PMID- 17344668 TI - Blood tests for asbestos-related mesothelioma. AB - Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30-40 years, and the prognosis is dismal. Recently, serum markers for the diagnosis of mesothelioma have been reported as candidates. In this paper, we mini-reviewed the potential utility of ELISA systems as serum diagnostic markers for asbestos-related mesothelioma. PMID- 17344669 TI - Efficacy of consolidation high-dose chemotherapy with ifosfamide, carboplatin and etoposide (HD-ICE) followed by autologous peripheral blood stem cell rescue in chemosensitive patients with metastatic soft tissue sarcomas. AB - BACKGROUND: Prognosis of patients with metastatic soft tissue sarcomas (MSTS) is poor even after response to doxorubicin-based chemotherapy. We report phase II data of high-dose chemotherapy and peripheral blood stem cell (PBSC) rescue in patients with MSTS responding to AI-G chemotherapy. PATIENTS AND METHODS: From 1997 to 2002, 55 patients with MSTS were prospectively treated with 4 cycles of AI-G (doxorubicin 75 mg/m(2), ifosfamide 6 g/m(2) with G-CSF support). Responders received 2 further cycles of AI-G with collection of PBSCs. High-dose chemotherapy consisted of ifosfamide 12 g/m(2), carboplatin 1.2 g/m(2) and etoposide 1.2 g/m(2) (HD-ICE) followed by reinfusion of PBSCs. RESULTS: Twenty one of 55 patients (38%) were assessed as responders (3 complete response, 18 partial response). All but 2 patients refusing treatment received high-dose chemotherapy with PBSC rescue leading to grade IV hematologic toxicity without severe infections in all patients. No toxic death occurred. After a median follow up time of 30 months, the median progression-free time was 12 months and survival time was 22 months for the entire group. By intent-to-treat analysis the probability of 5-year progression-free survival was significantly higher for patients allocated to HD-ICE compared to patients receiving second-line chemotherapy after failure of AI-G (14 vs. 3%; p = 0.003). The estimated 5-year overall survival between the 2 groups was different (27% vs. not reached) but did not reach significance (p = 0.08). CONCLUSION: HD-ICE is feasible and promising in patients with chemosensitive MSTS. A randomized phase III trial is warranted to further define the role of HD-ICE as consolidation treatment in these patients. PMID- 17344670 TI - Cost-effectiveness analysis of first-line chemotherapies in metastatic colorectal cancer. Results of the Federation Francophone de Cancerologie Digestive (FFCD) 9601 randomized trial. AB - BACKGROUND: The De Gramont regimen (or high-dose LV5FU2, HD-LV5FU2) is considered a standard treatment for metastatic colorectal cancer. The aim of the study was to evaluate the efficacy and the costs of three regimens as compared to HD LV5FU2: raltitrexed (R), LV5FU2 with a lower dose of folinic acid (LD-LV5FU2), and weekly infusional 5FU (WI-FU). METHODS: An economic analysis was performed prospectively as part of a randomized trial comparing first-line chemotherapy regimens in 294 patients with unresectable metastatic colorectal cancer. The primary endpoint was event-free survival (EFS). Direct medical costs were computed from the health system viewpoint using 2001 unit costs. RESULTS: None of the three regimens improved EFS as compared to HD-LV5FU2. R was less effective and more toxic. The mean total cost per patient was euro 15,970 for HD-LV5FU2. The cost of R (10,687 euro) was lower than that of HD-LV5FU2 (p = 0.008). The cost of LD-LV5FU2 (14,888 euro) and of WI-FU (13,760 euro) was not significantly different from that of HD-LV5FU2. CONCLUSION: The lower efficacy and increased toxicity of R made it a clinically inferior regimen despite its easy administration and lower cost. The HD-LV5FU2 protocol remains a better treatment. LD-LV5FU2 appeared a good alternative regimen because it reduced costs without jeopardizing its efficacy. The WI-FU regimen did not show a significant difference in terms of efficacy, but suggested toxicity to be slightly increased. PMID- 17344671 TI - Efficacy and tolerability of capecitabine with weekly paclitaxel for patients with metastatic breast cancer: a phase II report of the SAKK. AB - BACKGROUND: Paclitaxel and capecitabine have proven activity in the treatment of metastatic breast cancer (MBC). Paclitaxel increases the expression of thymidine phosphorylase, the enzyme that activates capecitabine. The purpose of this study was to evaluate the efficacy and tolerability of capecitabine in combination with weekly paclitaxel largely as first-line therapy in patients with MBC. PATIENTS AND METHODS: From April 2002 to September 2004, 19 patients with MBC received oral capecitabine (1,000 mg/m(2) twice daily on days 1-14) plus i.v. paclitaxel (80 mg/m(2) on days 1, 8 and 15) in a 21-day cycle for a maximum of 6 cycles. RESULTS: After a median follow-up of 19.3 months the overall response rate was 63% with 1 complete response (5%) and 11 partial responses (58%). Disease was stabilized in 1 patient (5%) and 3 patients had progressive disease (16%). Three patients were unable to be assessed for response to treatment. Median time to progression was 3.3 months, median time to treatment failure 3.0 months and median overall survival 13.8 months. A substantial number of patients experienced major side effects. The most common treatment-related adverse events were hand foot syndrome (53%; grade 3: 37%), alopecia (42%; grade 3: 26%), diarrhea (32%; grade 3: 11%) and neurotoxicity (32%; grade 3: 16%). Hematologic toxicities were uncommon. CONCLUSION: The combination of capecitabine and paclitaxel appears to be active in MBC but the safety profile with the dosages used in this trial was unacceptably high and led to a short time to treatment failure. However, based on the efficacy data alternative schedules deserve further evaluation. PMID- 17344673 TI - Sickle cell disease in the Kingdom of Saudi Arabia: East and west. PMID- 17344672 TI - Symptoms in the lives of terminal cancer patients: which is the most important? AB - OBJECTIVES: Symptoms other than their primary disease can interfere in the lives of terminal cancer patients. We sought to identify which of these symptoms is most important. METHODS: We administered a questionnaire, including the M.D. Anderson Symptom Inventory (MDASI), to 142 terminal cancer patients at the National Cancer Center, Korea. The validity of the MDASI was tested by principal axis factor analysis and Cronbach's alpha coefficient. Stepwise multiple regression analysis was used to determine the symptoms that interfered most in terminal cancer patients' lives. RESULTS: Factor analysis showed that it was composed of two factors (symptom and interference scales). Cronbach's alpha coefficients of symptom and interference scales were each >0.70. The patients had an average of 11 of 13 symptoms of the MDASI. Pain was the most common and severe, followed by feelings of distress and fatigue. Fatigue was the most highly correlated with interference sum. In stepwise multiple regression analysis, the most interfering symptom was fatigue. CONCLUSIONS: Although pain was the most common and severe symptom, fatigue was the most important symptom interfering in the lives of terminal cancer patients. In treating terminal cancer patients, healthcare providers should actively intervene to reduce both fatigue and pain. PMID- 17344674 TI - Neonatal screening for sickle cell disease, glucose-6-phosphate dehydrogenase deficiency and a-thalassemia in Qatif and Al Hasa. AB - BACKGROUND: Screening programs to determine the frequency of sickle cell, glucose 6-phosphate dehydrogenase deficiency and alpha-thalassemia gene are available in Saudi Arabia, although not used frequently. Greater use of these programs will decrease the morbidity and mortality of Saudi children affected by these disorders. PATIENTS AND METHODS: Neonatal hemoglobin electrophoresis and glucose 6-dehydrogenase fluorescent spot tests were performed on newborn babies delivered between December 1992 and December 1993 at the Qatif Central Hospital and at the King Fahad Hospital in Al Hasa. Cord blood samples were collected from babies born in these two hospitals. Babies born in other hospitals had blood collected in their first visit to Qatif primary care centers at the time of vaccination. All specimens were sent to Dammam Central Laboratory. The diagnosis of sickle cell and alpha-thalassemia was based on cellulose acetate electrophoresis and confirmed by agar gel electrophoresis, and glucose-6-phosphate dehydrogenase was confirmed by fluorescent spot test. RESULTS: A total of 12,220 infants, including 11,313 Saudis (92.6%), were screened over a 12-month period. The common phenotypes detected in these infants included AF, AF Bartas, SFA, SFA Bartas, FS and FS Bartas. In the Saudi infants, homozygous sickle cell disease was detected in 2.35% and 1.08% in Qatif and Al Hasa, respectively. The frequencies of sickle cell gene were 0.1545% and 0.1109% in Qatif and Al Hasa. alphathalassemia gene based on an elevated level of Hb Bartas were 28% and 16.3% in Qatif and Al Hasa. The screening for G6PD deficiency revealed a high prevalence of 30.6% and 14.7% in Qatif and Al Hasa. In the non-Saudi infants, the frequencies were low. CONCLUSION: The outcome of this study indicates that the Saudi populations in Qatif and Al Hasa are at risk for hemoglobinopathies and G6PD. Neonatal screening programs are essential and cost effective and should be maintained as a routine practice. PMID- 17344675 TI - Sickle cell disease in childhood in Madina. AB - BACKGROUND: Sickle cell disease (SCD) is a common disease in Saudi Arabia, with a high prevalence in the Eastern and Southern regions. This study reports on 53 cases of SCD encountered in the Madina area. PATIENTS AND METHODS: In a retrospective study of 6000 pediatric patients, 53 children (0.88%) with sickle cell disease were admitted in the Maternity and Childrenas Hospital at Madina, between November 1990 and October 1991. Of these, 39 patients (73.58%) were Saudis and 14 (26.41%) were non-Saudis. RESULTS: Thirty-six patients were homozygous SS and 17 were sickle thalassemic. The main causes of admission were vaso-occlusive crisis (77.35%), infection (67.92%), acute chest syndrome (22.64%), anemia (12.6%), and cerebrovascular accident (9.43%). The lowest and highest age groups recorded in this study were six months and 12 years, respectively. About 70% of the patients are still being followed up, and none of the patients has died. CONCLUSION: . This disease is one of the major causes of morbidity in this region of Saudi Arabia. Measures required include neonatal screening programs for the early detection of the disease, as well as research into new drugs to counter the disease. PMID- 17344676 TI - Epstein-Barr virus expression in Hodgkin's disease: Correlation with histologic subtypes and T and B lymphocyte distribution. AB - BACKGROUND: The pathogenesis of Hodgkinas disease (HD) has been linked to Epstein Barr virus (EBV). Some histologic subtypes show a high level of viral expression. These include mixed cellularity (MCHD) and nodular sclerosis (NSHD) subtypes. Grade II NSHD is a more aggressive variant of HD. Lymphocyte predominant (LPHD) is a B cell lymphoproliferative disorder that has not been associated with EBV expression. Infiltrating lymphocytes in HD are predominantly T lymphocytes, with a minor component of B lymphocytes. In the current study, EBV expression was tested in cases of HD in relation to histologic subtypes. An attempt was made at correlating EBV expression with T and B lymphocyte distribution in lymph nodes involved by HD. METHOD: Formalin-fixed paraffin-embedded tissue from 62 cases of HD were tested for EBV mRNA expression, using the EBER-1 probe and in situ hybridization. T and B lymphocyte distribution and their ratios were evaluated using antibodies to T and B lymphocytes (UCHL-1 [CD45 RO] and CD 20, respectively), and the immunoperoxidase technique. RESULTS: The cases were seen in 38 male and 24 female patients, with an age range of 3 to 72 years (median 25 years). There were 30 cases of grade I and 15 cases of grade II NSHD, 9 cases of MCHD and 8 cases of LPHD. EBV mRNA expression was seen in 29 cases (46%). This expression was seen in 8 cases of grade I NSHD (26%), 13 cases of grade II NSHD (86%) and 8 cases of MCHD (88%). None of the cases of LPHD showed viral expression. T to B lymphocyte ratios in EBV-positive cases ranged from 1/6 to 8/1, and ranged from 2/1 to 20/1 in EBV-negative cases (P=0.06). Nine of the 29 positive cases (31%) showed equal T/B lymphocyte ratios (n=4), or predominance of B lymphocytes (n=5). None of the EBV-negative cases showed predominance of B lymphocytes. CONCLUSION: Our study confirms previously reported findings of the prevalence of EBV expression in MCHD and NSHD. Our findings also suggest that EBV expression may be more commonly seen in aggressive forms of HD. Decreased numbers of T lymphocytes in these aggressive subtypes may suggest that a process of more profound T lymphocyte depletion is occurring in these cases, leading to uncontrolled EBV replication and more aggressive disease. PMID- 17344677 TI - Thrombolytic therapy in acute myocardial infarction: Experience at a university hospital in Kuwait. AB - BACKGROUND: There is conclusive evidence from large clinical trials that thrombolytic therapy reduces mortality and morbidity in acute myocardial infarction (AMI). However, only a small proportion of patients receive thrombolytic treatment. Estimates have varied from 20%-50% in North America and Europe. Data from the Arab Middle East is sparse. The purpose of our study was to determine the use of thrombolytic therapy in our hospital. METHODS: We conducted a retrospective analysis of 343 patients (358 incidents of AMI), who were either discharged from or died at the coronary care unit of the Mubarak Al-Kabeer Hospital during the one-year period between June 1994 and May 1995. RESULTS: Our patients were relatively younger (63% were 7lt;55 years) and had a much higher prevalence (44%) of diabetes compared to European patients. We observed a high rate (62%) of thrombolysis and a lesser shortfall (8%) when compared to that reported for European patients. The main reason for withholding thrombolytic therapy was non-diagnostic electrocardiogram (ECG) on initial presentation. Women were less likely to be thrombolyzed than men (38% vs. 66%, P=0.0001). Older patients (aged >65 years) were also less likely to be thrombolyzed than younger patients (42% vs. 66%; P=0.0006). CONCLUSION: We conclude that the use of thrombolytic therapy in this university hospital in Kuwait is appropriate. However, as observed in other reports as well, the underutilization of thrombolytic therapy in women and the elderly needs to be addressed in future studies. PMID- 17344678 TI - S-100 protein in the diagnosis of tuberculoid/borderline tuberculoid leprosy. AB - BACKGROUND: A definitive diagnosis of tuberculoid and borderline tuberculoid leprosy is based on a demonstration of either acid-fast bacilli or nerve elements within the granulomas. On routine hematoxylin and eosin stains, the nerve fibers are not easily identifiable. In this study, we used S-100 protein to highlight the nerve elements and to count their numbers in leprosy and non-leprosy granulomas. MATERIALS AND METHODS: Skin biopsy specimens from 15 cases of tuberculoid/borderline tuberculoid leprosy and 14 cases belonging to other granulomatous diseases of the skin were stained with S-100 protein. The surface area of all the biopsies was calculated and the number of nerve bundles stained with S-100 protein were counted in each specimen. RESULTS: The nerve bundles were 15 per cm 2 in leprosy cases, and 9.2 per cm2 in non-leprosy cases. In addition, the leprosy cases showed longer nerve twigs that were perpendicularly oriented to the skin surface. CONCLUSION: Immunostaining with S-100 facilitated detection of nerve elements in tuberculoid/borderline tuberculoid leprosy. Also, an increased number of nerve elements were found in leprosy granulomas when compared with non leprosy granulomas (P=<0.05). PMID- 17344679 TI - The Arabic self-reporting questionnaire (SRQ) as a psychiatric screening instrument in medical patients. AB - BACKGROUND: The self-reporting questionnaire was originally developed by the WHO in order to screen for psychiatic disorders. To assess the validity of the Arabic self-reporting questionnaire (SRQ) as a screening instrument for psychiatric morbidity in a sample of Saudi medical patients. METHODS: All patients referred for endoscopy underwent a semi-structured interview, and were then asked to fill out the SRQ. One hundred and sixty-six males and 126 females were included in the study. RESULTS: Sixty percent of the subjects were identified by the SRQ as psychiatric cases, compared to 48.6% identified using the psychiatric interview. A cut-off point between six and seven, was found to yield a sensitivity of 93%, a specificity of 70%, and a misclassification rate of 19%. Females had more psychiatric morbidity than males. CONCLUSION: The validity indices and receiver operating characteristic (ROC) analysis support the usefulness of the SRQ as a cost-effective screening instrument for psychiatric morbidity in a two-stage large population research. PMID- 17344680 TI - Genetics of small round cell tumors of children. PMID- 17344681 TI - Acute liver failure. PMID- 17344683 TI - Starting a liver transplantation program: Experience at King Fahad National Guard Hospital in Riyadh. PMID- 17344682 TI - What's your diagnosis: Homocysteinuria. PMID- 17344684 TI - Indinavir-induced diabetes mellitus. PMID- 17344685 TI - Imaging findings of spontaneous perforation of common bile duct in an infant. PMID- 17344686 TI - Left paraduodenal mesocolic hernia. PMID- 17344687 TI - The Hair-An sydnrome: A report of a misdiagnosed case with unfortunate outcome. PMID- 17344688 TI - Superficial femoral artery pseudoaneurysm secondary to bone exostoses. PMID- 17344689 TI - Atypical Kawasaki disease with coronary artery involvement. PMID- 17344690 TI - Permanent pacing of the heart via a coronary sinus branch. PMID- 17344691 TI - Road traffic accident admissions in the United Arab Emirates. PMID- 17344692 TI - Psychosocial impact on mothers of Saudi diabetic children in Riyadh, Saudi Arabia. PMID- 17344693 TI - Teratomas in infancy and childhood: A 10-year experience. PMID- 17344694 TI - Detection of b-thalassemia carriers in Jordan. PMID- 17344695 TI - Bactericidal activity of polymorphonuclear neutrophils in individuals severely deficient in glucose-6-phosphate dehydrogenase. PMID- 17344696 TI - Seroepidemiological prevalence of human T-cell lymphotropic virus type I (HTLV-I) among healthy blood donors in Eastern Saudi Arabia. PMID- 17344698 TI - Reply: Sacroliitis causing Salmonella typhi. PMID- 17344697 TI - Tuberculosis arthritis: A review of 27 cases. PMID- 17344699 TI - Varicella vaccine: A new era of live herpes vaccine. PMID- 17344700 TI - Sacroiliitis causing Salmonella typhi. PMID- 17344703 TI - Can breast cancer be prevented? PMID- 17344701 TI - Reply: Varicella vaccine: A new era of live herpes vaccine. PMID- 17344705 TI - The angiotensin-converting enzyme (ACE) gene insertion/deletion dimorphism tracks with higher serum ace activities in both younger and older subjects. AB - BACKGROUND: The absence of a 287 base pair alu sequence in the ACE gene (D allele) is associated with higher ACE levels than its presence (I allele) in adults. We carried out a case-control study of the ACE*I/D dimorphism in relation to circulating ACE activities to evaluate associations between the two variables in adults, compared to younger (18 years or less) individuals. MATERIALS AND METHODS: Genotypes of the ACE*I/D dimorphism were determined on DNA samples from a population of 164 random (unrelated) Emirate nationals, composed of two groups: 112 subjects above 18 years of age (range=20-77 years), and 52 subjects of 18 years or less (range=1-18), and analyzed for putative associations with serum ACE activities. ACE*I/D genotypes of the 164 individuals were determined by assays based on polymerase chain reaction. ACE activities were determined on serum samples of these subjects by colorimetric assays. RESULTS: The D allele was associated with increased ACE values in both adult and younger individuals. Mean ACE activity levels associated with II, ID and DD genotypes, however, were 42% 61% higher in the 18 years and under group of subjects. The ACE*I/D marker accounted for 28% of the variance of the phenomenon determining ACE levels in adults, and for 30% among youngsters. CONCLUSION: The ACE*I/D dimorphism correlated strongly with circulating ACE activities in both adult and young Emirati subjects, and the corresponding mean ACE activities were significantly higher among the youngsters. PMID- 17344707 TI - Pattern of congenital heart disease in the Southwestern region of Saudi Arabia. AB - BACKGROUND: The aim of this study was to assess the frequency of various forms of congenital heart disease (CHD) among affected children in the Southwestern region of Saudi Arabia. PATIENTS AND METHODS: During the study period (July 1994 to June 1996), 608 children were referred to Asir Central Hospital as having CHD. All the children were evaluated by a pediatric cardiologist and had electrocardiogram and echocardiogram. RESULTS: Of the 608 patients, only 335, comprising 162 males and 173 females, had CHD. The male to female ratio was 0.9:1. The frequency of various forms of CHD was as follows: ventricular septal defect (VSD) 32.5%; patent ductus arteriosus 15.8%; atrial septal defect 10.4%; pulmonary stenosis 10.1%; atrioventricular septal defect and mitral valve prolapse, 3.6% each; aortic coarctation/interruption 3.3%; obstructive aortic valve lesions 2.7%; tetralogy of Fallot 4.5%; common ventricle 2.7%; pulmonary atresia (PA) with VSD 1.8%; D-transposition of the great arteries 1.5%; Ebstein anomaly 1.5%; and isolated PA 1.2%. Other lesions were extremely rare. CONCLUSION: The distribution in this study is similar to that reported in previous studies from other parts of the world, except for the lower incidence of obstructive aortic valve lesions. PMID- 17344708 TI - The prevalence of rheumatoid arthritis in the Qassim region of Saudi Arabia. AB - BACKGROUND: Although rheumatoid arthritis (RA) of varying degrees of severity has been seen in our clinics, there is no statistical evidence of the magnitude of the problem in Saudi nationals. We conducted this study to determine the prevalence of RA in the Al Qassim Region of Saudi Arabia. PATIENTS AND METHODS: Five thousand eight hundred and ninety-one Saudi adults, aged 16 years and over, were studied in a house-to-house survey in the Al Qassim Region. RESULTS: Of the 5891 adults studied, 13 cases of RA were identified, using the criteria set for the diagnosis of RA by the American College of Rheumatology. Thirty-five percent of our patients showed positive rheumatoid factor. CONCLUSION: The prevalence of RA in Al Qassim was estimated at 2.2 per thousand people. It was also noted that the prevalence of the disease increased with age, and that it was more common in females. PMID- 17344709 TI - Peripartum hysterectomy: 10-year experience in two manitoba tertiary centers. AB - BACKGROUND: The aim of the study was to review the incidence, associated risk factors, indications and complications of peripartum hysterectomy in the two teaching hospitals of the University of Manitoba, Canada. PATIENTS AND METHODS: We conducted a retrospective study of all cases of peripartum hysterectomy that occurred over a 10-year period at the Health Sciences Centre (HSC), and over a five-year period at St. Boniface General Hospital (SBGH), the two tertiary centers in Winnipeg, Manitoba. RESULTS: Twenty-five peripartum hysterectomies were identified among 59,839 deliveries at both HSC and SBGH, for an overall incidence of 0.4/1000 births. Twenty-three hysterectomies (92%) were performed as emergency procedures, 19 (76%) followed a cesarean section (relative risk = 15), and 15 patients had single or multiple prior cesarean section scars (relative risk = 14.2). The indications for hysterectomy were: hemorrhage due to placenta/accreta (n=9); uterine atony (n=6); uterine rupture (n=5); retroperitoneal hematoma (n=2); and cervical laceration (n=1). Two cases were performed electively for cervical and ovarian cancer, respectively. Twenty-three women (92%) required blood transfusion, five (20%) had coagulopathy, four (16%) had bladder injuries, and three (12%) required salpingo-oophorectomy for uncontrolled adnexal bleeding. CONCLUSION: Our reported incidence for peripartum hysterectomy is lower than that reported elsewhere in the recent literature, while the risk factors for hysterectomy were similar to those reported. Although the maternal mortality was nil in this study, morbidity was high. PMID- 17344710 TI - The prevalence of hypertension in different geographical regions of Saudi Arabia. AB - BACKGROUND: The results of the National Nutrition Survey of the people of the Kingdom of Saudi Arabia showed that the prevalence of arterial hypertension (BP >/= 160/95 mmHg) among the adult population is 5.3% and 7.3% for systolic and diastolic hypertension, respectively. The objective of this study, which is part of the Survey, was to investigate if the diversified ecological nature of the life of the people of the Kingdom has an effect on the prevalence of arterial hypertension in the adult population in the different geographical regions of the Kingdom. MATERIALS AND METHODS: The Survey was population-based, employing cluster sampling methods and household visits by health teams trained by the same investigators to avoid individual variations and ensure data validity. 2,556 families with 17,892 individuals of all ages were randomly selected from 12 areas according to the population distribution all over the Kingdom. The total number examined for BP with complete data amounted to 13,700 individuals, of whom 6,260 were adults (over 18 years of age). The WHO definition of arterial hypertension was used. Also used was the definition of 140/90 mmHg. RESULTS: Systolic blood pressure hypertension (SBPH) showed a statistically significant difference (P<0.001) among the regions. The highest prevalence was found in Farasan (8.9%) and the lowest was reported from Asir (2.2%). There was a higher prevalence among females compared to males in the 40-75 year age group in all regions, except in the highlands of Al Taif and Asir. However, the difference was not statistically significant, except in Makkah (25.9%, P<0.001) and Al Sharikia (22%, P<0.03). Diastolic blood pressure hypert ension (DBPH) prevalence increased with age in all regions, except in males of Farasan, Makkah, and in females of Asir. The difference in the prevalence between regions was statistically significant (P<0.001). The highest DBPH prevalence (sexes combined) was reported from Al Qassim (10.6%) and the lowest from Makkah (4.2%). Using the definition of hypertension as 140/90 mmHg, the highest SBPH prevalence was reported from Makkah (sexes combined) (27.9%), while the lowest was from Makkah and Asir (22% each). The prevalence of SBPH and DBPH was insignificantly higher among females than males in eight and seven of the 12 regions, respectively. CONCLUSION: There is a statistically significant difference in the prevalence of SBPH and DBPH in the different regions of the Kingdom (P<0.001). The prevalence pattern tends to be fairly similar to that found in the affluent societies in the Western countries. PMID- 17344711 TI - Chromosome telomeres: The aging clock. PMID- 17344712 TI - Failure of fertilization following intracytoplasmic injection of round-headed sperm. AB - BACKGROUND: Intracytoplasmic sperm injection (ICSI) is a very effective technique for the treatment of male factor infertility, even in severe cases. An exception to this rule is round-headed acrosomeless sperm, for which there is an extremely low success rate. The objective of this study was to report our first experience with ICSI using round-headed spermatozoa. MATERIALS AND METHODS: A total of four infertile males with globozoospermia underwent the conventional ICSI program during the period from 1995 to 1997. Semen parameters were evaluated according to the WHO criteria. Twenty-eight oocytes were collected following conventional ovarian superovulation. RESULTS: Volume, pH, and viscosity of the semen were within normal range. Sperm counts and progressive motility were from >1 to 90x10 6 mL, and from 0% to 60%, respectively. Distinct 100% acrosomeless morphology was observed with Giemsa staining. Twenty-two metaphase II oocytes (78.6% of the total) from four ICSI cases were injected with the husbandas round-headed spermatozoa. Total fertilization failure was observed in all these cases. CONCLUSION: The results clearly demonstrate the important role of normal head morphology in activating the oocytes, as well as the need to develop a modified but safe ICSI technique, which will be effective in overcoming this severe type of male infertility. PMID- 17344713 TI - Recent trends in the treatment of cutaneous leishmaniasis. PMID- 17344714 TI - What's your diagnosis: Tumoral calcinosis. PMID- 17344715 TI - Airborne Alternaria spores: Potential allergic sensitizers in Saudi Arabia. AB - BACKGROUND: In order to investigate the role of airborne Alternaria spp. in the sensitization of individuals having respiratory allergy symptoms, particularly bronchial asthma, an aerobiologic and clinical (diagnostic) study was conducted at several centers in Saudi Arabia. MATERIALS AND METHODS: Airborne Alternaria spores were studied at four different centers in Riyadh, Jeddah and Al-Khobar, including three years at one site. Skin prick tests (SPT) were conducted on a total of 616 allergic individuals attending allergy clinics at six different hospitals in Abha, Qassim, Gizan, Jeddah, Hofuf and Makkah regions. RESULTS: Alternaria spores constituted between 1.9%-9.6% of the total fungal air spora, and the maximum concentration exceeded 5x10 2 spores per m3 of air in Jeddah, followed by 4.9x102 spores per m3 in Al-Khobar. Mean weekly and monthly concentration of Alternaria fluctuated, reaching up to 150 spores per m 3 and 60 spores per m 3, respectively. Quantitative regional variations were also recorded. IgE-mediated SPT reactivities conducted on allergic patients resulted in an overall 21.6% positive reactions, showing mild, moderate and strong wheal and erythema. CONCLUSION: The findings reveal that Alternaria spores are prevalent as a major component in the outdoor environment of the Kingdom, with peaks in April and October. The overall 21.6% positive SPT reactions indicate the sensitization level or cross-reactive sensitivity to Alternaria allergens. The study suggests that airborne Alternaria can be a potential allergic sensitizer in susceptible individuals and can be a risk factor in sensitized individuals with symptoms of bronchial asthma and allergic rhinitis in the Kingdom of Saudi Arabia. PMID- 17344716 TI - Factors affecting patient's choice of hospitals. AB - BACKGROUND: This study was conducted to determine the factors that influence a patient's choice of hospitals. PATIENTS AND METHODS: Through the use of a self administered questionnaire, data were collected from a random sample of 541 patients in two government and two private hospitals in Riyadh. Factor analysis was used to determine the underlying hospital-related and attitudinal dimensions that influence a patient's choice of hospital. Stepwise discriminant analysis was used to determine the factors that discriminate between patients who would prefer to seek treatment in a government hospital, and those who would prefer to be treated in a private hospital. RESULTS: The factor analysis revealed five underlying dimensions that influence a patient's choice of a hospital: convenient administrative procedures, quality of services, hospital image, cost of treatment, and health insurance coverage. After conducting stepwise discriminant analysis, eight variables appeared to be statistically significant in discriminating between patients who prefer government hospitals and those who prefer private hospitals. These variables were: cost of treatment, employment, quality of services, convenient administrative procedures, perceived state of health, health insurance coverage, age and sex. CONCLUSIONS: The results of this study indicate that the choice of hospital is influenced by sociodemographic variables as well as hospital attributes. This implies that the government should give more effective support for the continued growth of the private healthcare sector, and also encourage further development of private health insurance. PMID- 17344717 TI - Massive systemic air embolism following a blunt chest injury. PMID- 17344718 TI - Cutaneous zygomycosis due to Saksenaea vasiformis: Case report and literature review. PMID- 17344720 TI - Multiple myeloma with bone marrow crystal deposition and marrow fibrosis. PMID- 17344719 TI - Dyspepsia and Helicobacter pylori infection: Analysis of 200 Kuwaiti patients referred for endoscopy. AB - BACKGROUND: Dyspepsia is a very common symptom, and is the reason for most referrals for esophagogastroduodenoscopy (EGD). Peptic ulcer disease (PUD), gastroesophageal reflux and gastric cancer account for a minority of such patients. However, the majority have no significant endoscopic abnormalities (non ulcer dyspepsia). Recently, infection with Helicobacter pylori (HP) has been implicated in the pathogenesis of PUD and gastric cancer. Since HP can be diagnosed by noninvasive techniques, it has been suggested that endoscopy should be restricted to HP-positive patients who do not respond to empirical therapy with antimicrobials. The aim of this study was to establish the prevalence of HP among Kuwaiti dyspeptic patients referred for endoscopy and to determine whether demographic and clinical screening, or the presence of HP, can help distinguish groups of patients with significant gastroduodenal pathology from those with non ulcer dyspepsia. PATIENTS AND METHODS: Two hundred randomly selected Kuwaiti patients referred for endoscopy were evaluated prospectively. A detailed personal interview was conducted to establish the demographic and clinical profile of each patient and a diagnostic EGD was performed after the interview. Finally, antral mucosal biopsies were taken to determine the presence of HP. The pre-coded data were analyzed. RESULTS: The main endoscopic findings were normal (32%), non erosive antral gastritis (26%), duodenitis (17.5%), duodenal ulcer (11.5%), deformed bulb (4%), esophagitis (7%), and erosive gastritis (2%). The demographic and clinical characteristics of patients did not correlate with endoscopic findings. The overall prevalence of HP infection was 88.5%. There were no statistically significant differences in the prevalence of HP among patients with various endoscopic findings. CONCLUSION: HP infection is common in Kuwaiti dyspeptic patients referred for endoscopy, irrespective of their demographic and clinical features or the underlying cause of dyspepsia. Noninvasive methods to detect HP are not valid alternatives to endoscopy in the work-up of dyspeptic patients. PMID- 17344721 TI - Cytogenetic evaluation of 1000 cases of chorionic villus sampling. AB - BACKGROUND: Chorionic villus sampling (CVS) is used routinely as a first trimester diagnostic procedure for fetal karyotyping in at-risk pregnancies. The success of the procedure is dependent on the experience of the operator performing it. The objective of this study was to determine the relationship between an operatorcontrolled clinical and laboratory setting and the safety and reliability of CVS service. PATIENTS AND METHODS: One thousand patients had a CVS procedure for a variety of indications, such as advanced maternal age, previous child with chromosome abnormality, etc. Both transcervical and transabdominal procedures were performed, according to placental location and uterine environment. For cytogenetic diagnosis, direct and short-term cultures were set up according to standard laboratory protocol. RESULT: Cytogenetic results were obtained in 99.6% of studies with 94.5% normal (46,XX or 46,XY), with the remaining having a variety of numerical and structural chromosomal abnormalities. Maternal cell contamination was found in 2% of the first 262 cases, while the overall rate observed in the 1000 samples was 0.5%. Level II mosaicism was observed in 0.8% and level III mosaicism observed in 0.9% of cases, respectively. The overall rate of pregnancy loss of chromosomally normal pregnancies within 28 weeks of gestation was 2.8%. No limb reduction defects were seen in any infant post-CVS. CONCLUSION: Our record demonstrates that experienced operators can deliver a safe and reliable CVS service. PMID- 17344722 TI - Pulmonary histiocytosis X. PMID- 17344724 TI - Cardiac tamponade complicating spontaneous esophageal rupture. PMID- 17344723 TI - Assessment of indicators for predicting choledocholithiasis before laparoscopic cholecystectomy. AB - BACKGROUND: The objective of this report was to study the sensitivity of indicators used for predicting bile duct stones and their endoscopic removal before laparoscopic cholecystectomy. PATIENTS AND METHODS: A retrospective study was conducted on 104 patients who successfully underwent endoscopic retrograde cholangiopancreatogram (ERCP) before laparoscopic cholecystectomy at Riyadh Medical Complex between 1992 and 1994 (1412H-1414H). Six indicatorsajaundice, biliary pancreatitis, stones in bile duct on sonography, dilated bile duct (>7 mm) on ultrasonography, dilated bile duct with deranged liver function test, and deranged liver function test without jaundiceawere used for suspecting choledocholithiasis and endoscopic removal before laparoscopic cholecystectomy. RESULTS: Ultrasound correctly predicted bile duct stone in 75%, followed by dilated bile duct with deranged liver function test (46%). Clinical jaundice and biliary pancreatitis were equally sensitive indicators (42% each). Sensitivity of only dilated bile duct on ultrasonography in predicting duct stone was 36%. Deranged liver function without jaundice was the least sensitive (22%) of the predictors. Overall, these indicators correctly diagnosed bile duct stones in 34% of patients. CONCLUSION: Until laparoscopic exploration of bile duct or a noninvasive technique, such as magnetic resonance cholangiopancreatogram (MRCP), is widely available, these predictors will help in selecting patients with bile duct stones for preoperative removal. Other workers have suggested combining these indicators to improve the predictive value. PMID- 17344725 TI - Alkaptonuria: Case report and review of the literature. PMID- 17344726 TI - Coarctation of the aorta: A call for early detection. AB - BACKGROUND: Early repair of coarctation of the aorta (COA) is associated with few perioperative complications and better long-term outcome. Therefore, early detection and treatment of COA patients is extremely desirable. The aim of this study was to review our referral system, the effectiveness of neonatal screening examination, and orient physicians about this abnormality, the mode and age of presentation, differences in presentation between cases with isolated COA, and cases associated with other cardiac lesions. PATIENTS AND METHODS: This was a retrospective study of 61 inpatients admitted to our hospital between January 1989 and December 1996, who were found to have COA. Referral data was analyzed and compared to hospital cardiac evaluation findings. RESULTS: All the patients were referred after being symptomatic, but there was no suspicion of COA in any of the cases. One of the patients was referred by a pediatrician from a private clinic, and the rest by hospital pediatricians. Femoral pulse and cardiac murmur were commented upon in only three of the referral letters. Systolic pressure gradient (SPG) between upper and lower limbs and systolic hypertension were not commented on in any of the referral letters. SPG >/=10 mm Hg and systolic hypertension were found in 100% and 58% of the patients, respectively, upon evaluation in our center. SPG in patients with COA associated with other cardiac lesions was significantly lower than in patients with isolated COA (P=0.02). CONCLUSION: Increased awareness in our primary health physicians of the importance of the neonatal screening examination and of measuring blood pressure in the limbs to detect COA early is needed. Timing of the neonatal screening examination between the third day and the third week is recommended. Systolic pressure gradient is a reliable method to detect COA, and in the lower significant range (>/=10 mm Hg) is associated with complex cardiac lesion rather than isolated COA. PMID- 17344727 TI - Group a streptococcus osteomyelitis and septic arthritis following varicella: Case report and review of the literature. PMID- 17344728 TI - A logistic regression model to predict nodal malignancy among cases with lymphadenopahty. AB - BACKGROUND: Peripheral lymphadenopathy can be caused by benign and malignant diseases. In this logistic regression model, we attempted to identify the clinical findings predicting high probability of nodal malignancy. MATERIALS AND METHODS: Two hundred and twenty cases diagnosed by peripheral lymph node biopsy were studied. Of these, 164 had benign lymph node pathology, while the other 56 were malignant. The patientsa medical charts were reviewed and a logistic regression model used to identify physical signs and simple investigations that will predict nodal malignancy. RESULTS: Hard lymph node consistency, negative Mantoux test and positive abdominal ultrasound (showing hepatosplenomegaly with or without lymphadenopathy) were found to correlate with a higher probability of nodal malignancy. CONCLUSION: A logistic regression model is proposed to calculate the probability of lymph node malignancy at different ages and both sexes in relation to lymph node consistency, Mantoux test and abdominal ultrasound results. PMID- 17344729 TI - Prevalence of headache and migraine in schoolchildren in the United Arab Emirates. AB - BACKGROUND: The aim of this report was to study the prevalence of headache and migraine among schoolchildren in the United Arab Emirates, and to determine the relationship between headache and various factors, with special emphasis on migraine, and the impact of headache on school attendance. MATERIALS AND METHODS: A cross-section population study was performed over a period between October 1995 and June 1996. Subjects were selected by multistage stratified sampling procedure. Data was collected by screening questionnaires followed by clinical interviews. This involved children of 12 primary schools in AlAin, Dubai, and Sharjah Emirates, for a total of 1159 schoolchildren. RESULTS: The prevalence rate of headache was estimated to be 36.9%, and for migraine 3.8%. The study showed that the prevalence of headache increases with age, the highest rate being among 13-year-olds (17.5%). CONCLUSION: The prevalence rate of headache and migraine in our study was similar to that found in other parts of the world. However, cultural and social factors may play a role in determining the incidence rate in this region. PMID- 17344730 TI - Renal cysts and associated malformations in pediatric autopsy material. PMID- 17344731 TI - Drug-induced rhabdomyolysis. PMID- 17344732 TI - Tissue expansion: King Khalid University experience. PMID- 17344733 TI - Surgical management of breast cancer in Saudi Arabia: A call for improvement. PMID- 17344734 TI - Patterns of accidental poisoning in children in Jeddah, Saudi Arabia. PMID- 17344735 TI - Poisoning problem in Jeddah region. PMID- 17344736 TI - Role of Wallstent(R) in urethral stricture. PMID- 17344737 TI - Tyrosinemia type II: Report of the first four cases in Saudi Arabia. PMID- 17344738 TI - Atypical scabies in systemic lupus erythematosus. PMID- 17344739 TI - Pseudomonas aeruginosa in hospitalized patients with infective exacerbations of bronchiectasis: Clinical and research implications. PMID- 17344740 TI - Impetigo herpetiformis: An obstetric concern. PMID- 17344741 TI - Stroke among sickle cell disease patients in Madina Maternity and Children's Hospital. PMID- 17344742 TI - Pulmonary hemosiderosis in an infant with psoriasis. PMID- 17344743 TI - Sirenomelia without vitelline artery steal. PMID- 17344745 TI - Clinical profile of Bell's palsy in the Qassim region. PMID- 17344744 TI - Bowel intussusception in a patient with human immunodeficiency virus infection. PMID- 17344746 TI - A rare case of neonatal alloimmune thrombocytopenia due to ANTI-HPA-2b. PMID- 17344747 TI - Ruptured hepatocellular carcinoma. PMID- 17344748 TI - Malignant chylothorax treated by talc pleurodesis: A case report and review of the literature. PMID- 17344749 TI - Intravascular large-cell lymphoma: Report of an unusual case. PMID- 17344750 TI - Anorexia nervosa with pancytopenia. PMID- 17344752 TI - Effects of fasting during Ramadan on compliance with medical treatment. PMID- 17344751 TI - Acute leukemia in King Fahad General Hospital, Jeddah. PMID- 17344753 TI - The pattern of skin diseases in Hail Region, Saudi Arabia. PMID- 17344755 TI - Profile of chronic headache patients in the Asir Region: A three-year study in Asir Central Hospital, Abha. PMID- 17344757 TI - Pattern of referrals from a general hospital to a regional tertiary health institutions: Samtah experience. PMID- 17344759 TI - Reply: Methemoglobenemia induced by accidental ingestion of nitrite. PMID- 17344760 TI - Methemoglobinemia induced by accidental ingestion of nitrite. PMID- 17344761 TI - Reply: Genotyping of hepatitis C virus isolates from Saudi patients. PMID- 17344762 TI - A late presentation of postpneumonectomy pleural empyema and bronchopleural fistula. PMID- 17344763 TI - Genotyping of hepatitis C virus isolates from Saudis patients. PMID- 17344769 TI - Prevalence and predictors of poor antihypertensive medication adherence in an urban health clinic setting. AB - Poor medication adherence may contribute to low hypertension control rates. In 2005, 295 hypertensive patients who reported taking antihypertensive medication were administered a telephone questionnaire including an 8-item scale assessing medication adherence. Overall, 35.6%, 36.0%, and 28.4% of patients were determined to have good, medium, and poor medication adherence, respectively. After multivariable adjustment, adults younger than 50 years and 51 to 60 years were 1.39 (95% confidence interval [CI], 0.56-3.42) and 1.53 (95% CI, 0.64-3.66), respectively, times more likely to be less adherent when compared with their counterparts who were older than 60 years. Black adults and men were 4.30 (95% CI, 1.06-17.5) and 2.45 (95% CI, 1.04-5.78) times more likely to be less adherent, respectively. Additionally, caring for dependents, an initial diagnosis of hypertension within 10 years, being uncomfortable about asking the doctor questions, and wanting to spend more time with the doctor if possible were associated with poor medication adherence. The current study identified a set of risk factors for poor antihypertensive medication adherence in the urban setting. PMID- 17344770 TI - Relation between insulin secretory capacity and microangiopathy in young diabetic patients in Bangladesh. AB - The pathogenesis of diabetic retinopathy is still unclear. The relative role of duration of diabetes, glycemic and insulinemic status in the etiopathogenesis of retinopathy is to be clearly understood. Hypertension, hyperlipidemia, pregnancy and age at diagnosis have been thought to be factors associated with diabetic retinopathy. Taking advantage of the availability of a group of young lean, normotensive and generally normolipidemic subjects in Bangladeshi population, the present study was undertaken to investigate the relationship between insulin secretory capacity and microvascular damage in the pathogenesis of diabetic retinopathy. A total number of 91 diabetic subjects, diabetes diagnosed before the age of 30 years, were recruited form the out-patient Department, BIRDEM Hospital. Diabetic subjects recruited were new- to previously diagnosed cases with duration of diabetes around 8 years. Insulin secretory capacity was assessed by C-peptide and C-peptide was estimated by ELISA method. Urinary albumin was measured by Immunoturbidetric methods. The subjects were grouped on the basis of duration of diabetes and presence (DR) and absence (NDR) of diabetic retinopathy. Subjects were also divided on the basis of albumin-creatinine ratio (ACR) level. ACR level was observed sharply increased with the duration of diabetes and showed a peak after 8 years. In the ACR positive cases 95.25% of diabetic patient had retinopathy. Both retinopathic and ACR positive subjects had low insulin secretory capacity as evident by absolute C-peptide level and C-peptide glucose ratio. Retinopathy was found increased with generalized vasculopathy. Both microvasculopathy and retinopathy seemed to occur at around 8 years. Insulin secretory capacity in particular seemed to have predominant determinant effect in the etiopathogenesis of diabetic retinopathy. PMID- 17344771 TI - Evaluation of objective structured practical examination and traditional practical examination. AB - To evaluate the competency of Objective Structured Practical Examination (OSPE) as an assessment technique compared to Traditional Practical Examination (TDPE) in assessment of laboratory component of physiology, the results of Physiology practical examination of 400 students from 4 Medical Colleges, two Government and two non Government (Dhaka Medical College, Mymensingh Medical College, Bangladesh Medical College, Uttara Women's Medical College) under Dhaka University were studied. Students' performance in OSPE and TDPE was compared. Mean score obtained in OSPE was 77.72+/-0.66 and found significantly higher than that for TDPE (64.44+/-0.61). Again mean scores achieved in OSPE were compared among different Medical Colleges and significant difference was noted. In OSPE, male students achieved significantly higher score than that of female students, especially in responding question station. The outcome of the present study thus indicates that OSPE is a better choice as an assessment technique over the Traditional method measuring wide range of practical skill. It may be concluded that it is important for competency based performance discrimination and it also helps improving students performance quality in laboratory exercise. PMID- 17344772 TI - Role of cardiac troponin I in staging and prognosis of congestive heart failure subjects. AB - Congestive heart failure is the one of the major cardiovascular disorder that is increasing in incidence and cause of death globally. Mortality rate has increased 40%-50% in advanced cardiac failure and 15%-25% in mild to moderate cardiac failure within one year of diagnosis. There is no established biochemical marker for the diagnosis, prognosis and staging of heart failure. Cardiac Troponin I may be a novel useful tool in identifying patients with Heart failure who are at increased risk for progressive ventricular dysfunction and death. Thirty six congestive heart failure cases and thirty six healthy controls were included in this study and serum cardiac troponin I and Ejection fraction were measured. All the study subjects were grouped according to the NYHA class they belong. Cardiac troponin I was significantly higher in CHF cases than the controls. Troponin I also significantly differed among groups. EF of cases was significantly lower than the controls and also differed among groups. A significant negative correlation between cardiac troponin I and progressive decline of ejection fraction was evident in this study. Cardiac troponin I increased progressively with progression of heart failure. Thus, Cardiac troponin I could be used to stratify patients undergoing heart failure in to high and low risk groups for future cardiac events. Cardiac troponin I could also be used as a very important marker for the prognosis of the patients with congestive heart failure. PMID- 17344773 TI - Effects of substance P on spontaneous contraction in the flexure region of the guinea pig colon. AB - Effects of Substance P on spontaneous contractions of the circular muscle of the flexure region of guinea pig colon were studied by mechanical tension recording. Substance P (3 nM-10 nM) produced tonic contraction associated with phasic activities but the contraction was found stronger at higher concentration. Verapamil (3 microM), a voltage dependent L-type Ca(2+) channel blocker completely blocked the spontaneous activities and also Substance P induced contraction. These results suggest that Substance P produce contraction by Ca(2+) influx and the Ca(2+) influx occurs by activating verapamil sensitive Ca(2+) channel. PMID- 17344774 TI - Characteristics of patients admitted with stroke. AB - Population based study on stroke morbidity and mortality is lacking in our country. We described the clinical pattern of patients with stroke admitted in Neuromedicine Unit, Chittagong Medical College Hospital, Bangladesh. One hundred and six consecutive patients were included in the study. Clinical diagnosis of stroke, initial assessment, and assessment of outcome of stroke were performed by the neurologists. On admission blood glucose, and creatinine level was estimated, and an electrocardiogram was recorded. Fasting lipid level estimation and CT-scan of brain were performed for patients who could afford the cost. The mean age of the patients was 60.0 +/-13.7 years and the highest occurrence of stroke was found in the age group of 61 - 70 years. The proportions of rural, semiurban and urban patients were 46.2%, 27.4% and 26.4% respectively. A large portion of the patients were found illiterate (47.2%), and only one patient had postgraduate education. The average per capita income was found 1159 +/-762 taka per month. About one-fourth of the patients had diabetes (21.7%). Hypertension, ischemic heart disease and dyslipidemia were found in 59.4%, 18.9% and 11.3% respectively. The cause of hospitalization was altered consciousness (58.5%), right hemiplegia (32.1%), and left hemiplegia (31.1%) either alone or in combination. The mean duration of hospital stay was 5.25 +/-2.19 days. Fifty percent partially and 35% satisfactorily recovered, and 7 (6.6%) patients expired. Patients from lower socioeconomic group were admitted in the hospital. A considerable number of stroke patients had hypertension and diabetes. PMID- 17344775 TI - Comparative study of radical neck dissection vs. modified radical neck dissection in metastatic neck gland. AB - Treatment of metastatic neck gland is an integral part of management of Head and Neck cancers, because this is the single most important prognostic determining factor. Although surgery and radio therapy with or without chemotherapy are the modalities available for treating neck gland, wide surgical excision of the whole regional lymphatic chain enblock is mostly favored. Radical Neck dissection is the operation for such disease, designed in the early part of twentieth century, still has got the validity, but a modification of that (modified radical neck dissection) is becoming popular for last few decades to reduce morbidity. In this study we compared 15 cases of radical neck dissection and equal number of modified radical neck dissection to observe the selection criteria of these two types of operations, their complications and therapeutic success. Neck deformity, shoulder pain and restricted shoulder movement are the major morbidities which are less in modified radical neck dissection. The oncologic efficacy appears as same in both procedures. PMID- 17344776 TI - Wilson's disease with hepatic presentation in childhood. AB - Diagnosis of Wilson's disease with hepatic presentation in childhood using clinical and common laboratory parameters is still challenging and is often missed or delayed. The aim of the study was to document the clinical and laboratory parameters of hepatic presentation of Wilson's disease in children. The study was conducted at a tertiary-care hospital in a developing country. Clinical and common laboratory parameters were recorded in 32 Wilson's disease children with hepatic presentation. The diagnosis was based on positive family history, Kayser-Fleischer ring, low serum ceruloplasmin level, elevated basal urinary copper excretion and favorable response to therapy with D-penicillamine. Mean age+/-SD at presentation was 9+/-2.97 years and 21 (65.6%) were boys. Chronic liver disease (21; 65.6%) followed by fulminant hepatic failure 1(6; 18.8%) were the commonest presentation. In the whole group, Kayser-Fleischer ring was found in 21 (65.6%), low serum ceruloplasmin in 16 (50%) and elevated basal urinary copper excretion in all 32 (100%) children. Diagnosis of Wilson's disease was made at presentation on the basis of i) Kayser-Fleischer ring, low serum ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 11 (34.4%), ii) Kayser-Fleischer ring, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 10 (31.2%), iii) elevated basal urinary copper excretion and favorable response to D penicillamine therapy in 6 (18.8%) and iv) low ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 5 (15.6%) children. Wilson's disease can not be excluded in children presenting with hepatic involvement using the commonly practiced clinical and laboratory parameters. A combination of various clinical and laboratory parameters were used for the diagnosis of Wilson's disease in the studied children with hepatic presentation. PMID- 17344777 TI - Effect of therapeutic ultrasound on calcific supraspinatus tendinitis. AB - Calcific tendinitis is an important cause of shoulder pain. There are various modalities used to treat calcific tendinitis. Ultra-Sound therapy (UST) is a non invasive modality of treatment. It is not costly. The aims of the present study were to see the efficacy of UST on calcific tendonitis. This was a prospective study done at BSMMU, BIRDEM and Rangpur Medical College Hospital. All the cases with duration of illness more than three months, and diameter of stones more than 5mm were included in this study. Out of 26 cases 10(38%) were male, 14(54%) were housewife, 8(31%) were businessmen. UST were given to all cases for 10 minute with 1 to 1.5 W/sq cm for 12 doses. After 12 doses of UST all the patients became free from pain and restriction of movements. Radiographs of 24(92%) cases showed no calculi. Only two patients showed clinical improvement only but radiographs showed no change in caiculi and symptoms returned after one and two months respectively. PMID- 17344778 TI - Histomorphometric study of thyroid gland of Bangladeshi people. AB - To study the histomorphological features of thyroid gland of Bangladeshi people in different age groups, thirty postmortem thyroid glands were collected and fixed in Bouin's fluid. For histological examination specimens were processed and stained following standard procedure and studied under low and high magnifications. Diameter of thyroid follicle and number of follicles per square millimeter were measured. Values were noted in a tabulated form and analyzed by SPSS program and findings were compared with the other studies of Western and Bangladeshi researchers and of standard textbooks. In this study it was observed that diameter of follicles were widely variable. The highest mean diameter of the follicles was found in 19 to 45 years age group and thyroids of this age group had fewer follicles per unit area of thyroid section than the two other groups. This difference was statistically significant with above 45 years age group (p=.001) and upto 18 years age group (p=.01) of the study. It was observed that all these findings of this geographical area were conformed to the findings of the other studies. PMID- 17344779 TI - Clinico-pathological study in large posterior fossa midline tumors. AB - This cross sectional analytic study was carried out among the admitted patients of the department of Neurosurgery, Bangabandhu Sheikh Mujib Medical University, Dhaka during the period of 1st July 2002 to 31st December 2004. The age ranged from 2.5 years to 70 years. The size of all posterior fossa tumors at presentation were more than 3 cm and the mean size of posterior fossa tumor was 4.38 cm. 62% of posterior fossa mid-line tumors were mixed density in NECT (non contrast CT). Regarding enhancement characteristics, mild-moderate enhancement and marked heterogeneous enhancement was equally distributed 46% followed by marked homogeneous enhancement only 08%.. The calcification was present only in 07 (14%) patients and most of them were ependymoma. Histopathologically, medulloblastoma was the common variety (32%). The CT scan diagnostic modality sensitivity, accuracy and positive predictive value were 100%, 84.78% and 84.78% respectively but in MRI diagnostic modality 100%, 91.30% and 91.30% respectively. PMID- 17344780 TI - High resolution ultrasound of ophthalmic patients in a tertiary hospital. AB - The study was done to find out pathologic processes in ophthalmic patients in different age group to understand the use, role and limitations of ultrasonography in the diagnosis of ocular pathology in this locality. A prospective study was done on total 143 patients from September 2004 to January 2006 who attended Centre for Nuclear Medicine & Ultrasound, Mymensingh for ultrasound evaluation of eye. Total 100 (69.93%, n=100) cases were male and 43 (30.06%, n=43) cases were female. The age ranges were 2 months to 80 years. A variety of ocular pathology was diagnosed with the help of high resolution ultrasound (HRUS) with unique ultrasound appearance. Bulk of the referral patients had history of ocular trauma (38.46 %, n= 38) and most commonly detected pathology in these group are vitreous hemorrhage (34.44%, n=34) and cataract formation (28.28%, n=28). Almost all of the patients did not have conclusive diagnosis clinically and by conventional means available before ultrasonography were performed. High resolution sonography may be used as a valuable tool for evaluation of ophthalmic pathology as a well suited, noninvasive method, and only practical imaging modality for assessing those cases particularly when light conducting media are opaque. PMID- 17344781 TI - Effects of long term iodized table salt consumption on serum T3, T4 and TSH in an iodine deficient area of Bangladesh. AB - The effect of iodized and non-iodized table salt in goiter hyper-endemic area on the thyroid gland and its hormones T3, T4 and Thyroid Stimulating Hormone (TSH) were studied in two hundred subjects from the Center for Nuclear Medicine and Ultrasound, Mymensingh. Iodized and non-iodized salt users were called study and control groups respectively. The mean concentration of T3 were 2.38 nmol/L and 2.22 nmol/L & T4 concentration were 128.67 and 123.72 nmol/L in the study and control group respectively. The mean TSH concentration was 1.52 mIU/L and 1.62 mIU/L in study and control group. The data indicated that continuous and long term use of iodized salt increased both T3, T4 and decreased TSH in such a limit which was not statistically deferent at P< 0.05 level as compared to the control group. There was no significant change in occurrence of (hypo and hyper thyroidism or iodinated salt induced thyrotoxicosis) adverse effect, following iodine supplementation. The study shows that, mandatory mass iodination of table salt consumption in a hyper-endemic iodine deficient area is safe and does not cause any side effect. We suggest close regular monitoring of T3, T4, and TSH and further evaluation by specifically designed studies for any probable link between iodine induced hypo or hyperthyroidism and mass iodination of table salt consumption. PMID- 17344782 TI - Healthy aged persons had a better adrenocortical function. AB - The present study was carried out in the department of physiology, Mymensingh Medical College, Mymensingh, Bangladesh during the period of July 2004 to June 2005 to estimate basal cortisol level in healthy aged persons and to explore association between aging and antiaging and adreno cortical status. A total number of 60 healthy subjects aged 60 and above 60 years old were included in this study. Twenty three (23) normal healthy subjects of aged 20-30 years were taken as control group. Estimation of serum cortisol level of both study and control group was done by radioimmunoassay (RIA) in centre for nuclear medicine and ultrasound, Mymensingh Medical College Hospital, Mymensingh, Bangladesh. Statistical analysis was done by SPSS program using unpaired students't' test between two groups. The results showed that there is no statistically significant difference in mean serum cortisol level of study group when compare to control group. The study depicts that subjects possessed better adrenocortical function and seems to be associated with good health and a high level of function despite advancing age. PMID- 17344783 TI - Summative assessment of under graduate medical student's performance in physiology by structured oral examination. AB - To evaluate the importance and efficiency of structured oral examination (SOE). This is a retrospective study, has been designed to compare the newly adopted structured oral examination (SOE) with that of the traditional oral examination (TOE). This study was conducted at the department of physiology during the year 2006, on 607 2nd year medical students of Mymensingh Medical College and 106 students from some other medical colleges who appeared in the first professional examination under Dhaka University from 2003-2006. For this purpose, scores achieved by the students in physiology in first professional examination for 4 successive years (2003-2006) were analyzed. The examinations in (2003-2004) and (2005-2006) were conducted under TOE and SOE respectively. Mean score achieved in SOE and TOE was 67+/-.02 and 57+/-.003 respectively. The difference is statistically significant. The pass percentage in SOE is 94.70% and 90.3% in TOE and the difference is significant. Maximum number of students in SOE attained score in the range of 60-69 but in TOE scores attained by maximum frequency fall in the range of 50-59. This observation indicates improvement in student's performance by quality and success rate in SOE. Therefore SOE is a more effective, skill full technique and superior to TOE in assessing student's competency and cognitive ability. The need and skill of SOE over the TOE in assessing oral part of examination has been proved. PMID- 17344784 TI - Studies on serum lipid profile in hypertensive patient. AB - The study was carried out to appraise the serum total cholesterol, triglyceride, HDL-C and LDL-C values in hypertensive patients for providing information to the health-policy planners and also to the clinical practitioners about the importance of routine monitoring of lipid profile in hypertensive patients for prevention of coronary heart disease and other consequences to combat morbidity and mortality and to reinforce the need to consider these parameters in daily clinical practice. It was a cross-sectional study. The study was conducted at Department of Physiology and Biochemistry of Mymensingh Medical College, Medicine Unit of Mymensingh Medical College Hospital and in the community of Sadar, Mymensingh District. The period of the study was January 2005 to December 2005. A total number of seventy subjects were included in this study. Out of them 40 (forty) were hypertensive patients and 30 (thirty) were normotensive & healthy controls. Most of the hypertensive patients (65%) were taking treatment irregularly. Serum total cholesterol, serum triglyceride and serum LDL cholesterol were greater in hypertensive than those of normotensive . The differences of mean of serum total cholesterol, serum LDL cholesterol in between two groups were statistically significant and in case of serum triglyceride it was statistically highly significant. Serum HDL cholesterol was less in hypertensive than those of normotensive. The differences of mean of serum HDL cholesterol in between two groups were statistically highly significant. Among 40 hypertensives the number of "Getting treatment- regular" & "Getting treatment irregular" was 14 (35%) & 26 (65%) respectively and the values are not statistically significant. Similarly in patients "suffering less than 5 years" and "suffering 5 years & above" the differences are also not statistically significant. CONCLUSION: The observations of this study has revealed that most of the hypertensive patients are taking treatment irregularly and there was significant alteration of serum cholesterol, triglyceride, HDL-C and LDL-C in hypertensive patients. Therefore, for routine monitoring of hypertensive patients to prevent the coronary heart disease (CHD) and other consequences, the reinforcement of the investigations of these parameters may be recommended in daily clinical practice. PMID- 17344785 TI - Evaluation of total hip replacement. AB - This prospective study was made to asses the results of total hip replacement done primarily at Dhaka Medical College Hospital by the surgical team from its orthopaedic department. Eight patients were selected randomly from April/2005 to December/2005. Six patients were male and two females. Age of the patients was ranging from 22 to 67 years with average of 37.4+/-5.12 (mean+/-SE) years. Majority of the patients (75%) were diagnosed as Aseptic necrosis of femoral head with secondary osteoarthritis. The femoral head was replaced by metallic component with C-stem and the acetabular cup made up of Ultra-High density Polyethylene. Both the components were cemented (methylmethacrylate) by hand packing. The patients were followed-up for 7.75+/-6.1 months (mean+/-SE) ranging from 4 months to 1 year. The results were evaluated on the basis of Harris Hip Score(2). 75 % had good to excellent and 12.5% had fair results. One patient complicated with dislocation and ultimately had poor result. The quality of life in seven patients (87.5%) improved much for which they were grateful. PMID- 17344786 TI - Histopathological analysis of hysterectomy specimens. AB - The objective of this study was to explore the histopathological findings and the rate of removal of ovaries in hysterectomy specimens. This study took into account 328 hysterectomy specimens examined in the Department of Pathology, Mymensingh Medical College and in one private Pathology Laboratory in Mymensingh town from March to August, 2005. Formalin fixed paraffin embedded tissue sections stained with haematoxylin and eosin were examined under light microscope. Patients' age, parts of uterus examined and their histopathological findings were retrieved from laboratory records. The common histopathological findings were: chronic cervicitis (87.80%), leiomyoma (17.07%), uterine prolapse (16.72%), adenomyosis (3.96), non-specific endometritis (3.35%), squamous cell carcinoma of cervix (2.44%), endometrial polyp (2.44%), serous cystadenoma of ovary (2.44%) and endometrial hyperplasia (1.83%). Some of the specimens show more than one lesions in the body of uterus, of which coexistence of adenomyosis and leiomyoma was the most common. Neoplastic lesions in cervix were 4.27%, in body 16.92% and in ovaries 5.06%. Malignant neoplasms were found in cervix 71.43%, in uterine corpus 3.03% and in ovaries 25%. Ovaries of both sides were removed in 48.17% of total cases. Their median age was 45 years, lowest age 23 years and maximum age was 82. The rate of removal of both ovaries was found to be increasing with the increase of age. Only one case was found to be subtotal hysterectomy and others were total hysterectomy. The present study revealed that the most common histopathological cause of hysterectomy is chronic cervicitis. Most common neoplastic cause of hysterectomy is leiomyoma. The rationalities and the possible after effect of hysterectomy in sexual functions and other physiological impairment should be followed up. PMID- 17344787 TI - Study on 40 cases of rickettsia. AB - Rickettsia is emerging in the subcontinent and clinically presents as non specific febrile illness. At present there is no cheap & easily available diagnostic tool in our hand. Beside this, Weil-Felix test is becoming abandoned. So, high index of clinical suspicions is essential to diagnose rickettsia at early stage and to prevent mortality & morbidity. 40 cases were recorded among the admitted febrile patients in MMCH since 2003 to 2005. Cases were selected by clinical suspicions; exclusions of other common febrile illness & thereafter supported by lab. Investigations, specially by positive Weil-felix test. Cases were distributed through out the year but 19 (47.5%) cases were detected in March to May. 12 (30%) cases were found in August to October. The remaining 9 cases were detected in the rest 6 months. All (40) cases were presented with fever (100%), headache was present in 33 (82.5%) cases, rashes were present in 15 (37.5%) cases, isolated splenomegaly was found in 15 (37.5%) cases & hepatosplenomegaly in 12 (30%) cases, arthralgia in 13 (32.5%) cases, lymphadenopathy in 5 (12.5%) cases; 2 (5%) cases attended with unconsciousness & epistaxis in 1 (2.25%) case. Scrub typhus were 19 (47.5%), Indian tick typhus 16 (40%), 5 (12.5%) cases were with dual pathology and were associated with enteric fever. 15 (37.5%) cases were treated with tetracycline only. 20 (50%) cases with only doxyclycline & 5 (12.5%) cases with tetracycline and ceftriaxone as these cases were associated with enteric fever. All patients (100%) cured with treatment. PMID- 17344788 TI - Alteration of serum copper in Kala-azar patients during SAG therapy. AB - We conducted an analytic case-control study in Kala-azar patients during Sodium Antimony Gluconate (SAG) therapy to assess the changes in serum copper. A total of 89 subjects were included in the study. Diagnosed patients of Kala-azar with parasitological evidence of Leishmania Donovani (LD) bodies in bone marrow, were selected as cases (n=54). They were selected from Medicine and Paediatric wards of Mymensingh Medical College Hospital, Mymensingh and nearby Fulbaria upazila of Mymensingh district. Physically healthy volunteers of similar age, sex and body mass index (BMI) as cases, were included in control group (n=35). The study period was from July 2003 to June 2004. SAG was given intramuscularly (20 mg/kg/day) to Kala-azar patients for 30 days. Blood samples were collected from controls, Kala-azar cases before therapy and same cases during 15-20 days of SAG therapy. Serum copper was higher in cases before therapy than those of controls (p<0.001). However, serum copper reduced significantly (p<0.001) during SAG therapy. So biochemical monitoring may be considered in the management of the disease. PMID- 17344789 TI - Oyster mushroom reduced blood glucose and cholesterol in diabetic subjects. AB - It has been postulated that mushroom has beneficial effect of lowering blood glucose and cholesterol in diabetic subjects. The literature so far searched and found that there was no published data in this regard. This study was undertaken to assess the effect of reducing blood glucose, cholesterol and triglycerides in diabetic patients. Additionally, this study addressed whether there was any hepatic and renal toxicity of mushroom. This clinical investigation was conducted in BIRDEM hospital from July 2005 to January 2006. Eighty-nine subjects were recruited. Baseline investigations included height, weight, blood pressure (SBP, DBP), plasma glucose for fasting (FPG) and 2-h after-breakfast (2hPG), total cholesterol (T-chol), triglycerides (TG) and high-density lipoprotein (HDL-c). Twenty- four days' study constitutes 7-days mushroom, 7-days no mushroom and then 7-days mushroom. Investigations were done at the start and each after every 7 days. Thirty subjects (M / F = 17 / 13) followed to ensure full compliance with the designed protocol for 24 days. The mean (SD) age of the participants was 46.3 (10) years. Mushroom significantly reduced systolic and diastolic blood pressure (SBP, p<0.01; DBP, p<0.05). It also lowered both plasma glucose significantly (FPG & 2-hPG, p<0.001). Mushroom also lowered total cholesterol and TG significantly; whereas, there was no significant change in weight and HDL-c. When mushroom was withdrawn, there were significant increases of DBP, FPG, 2hPG, T cholesterol and TG, whereas, no significant change was observed in weight, SBP and HDL-c. Restarting mushroom there was again significant reduction of blood glucose, TG and cholesterol. We conclude that mushroom significantly reduced blood glucose, blood pressure, TG and cholesterol of diabetic subjects without any deleterious effect on liver and kidney. The effect of mushroom may be investigated in a large sample for a longer duration to evaluate its efficacy and toxicity. PMID- 17344790 TI - Olmsted syndrome. AB - Olmsted syndrome is a rare disorder characterized by symmetrical sharply marginated mutilating keratoderma of palms & soles & hyperkeratotic plaques around the body orifices, onychodystrophy, ainhum & amputation of digital phalanges, flextion deformities of the fingers, localized alopecia, leukokeratosis of the tongue, shortness of stature & laxity of large joints. Inheritance is autosomal dominant, although sporadic cases have been reported. Here we describe two cases of this rare disorder with thickened hyperkeratotic lesion over palm & soles & along with amputation of 3rd , 4th & 5th toes in one case. In one of our case (case no. 2) the immediate younger brother has got the same disease. Both of them were treated with tab. Neotegason 25 mg orally daily for 3 months & there was significant improvement after treatment. PMID- 17344791 TI - Male urethral cancer. AB - A 55 years old man presented with long standing voiding obstructive symptoms like poor stream, frequency of micturition, straining at micturition and a sense of incomplete evaluation since 2002. He was clinically diagnosed a case of stricture urethra. Later he developed a swelling in the penoscrotal region with retention of urine in March 2005 and was treated by dilatation. But on removal of the catheter he developed retention again for several times and ultimately for gross periurethral sepsis, urinary diversion was required in May 2005. In October 2005, biopsy from the scrotal abscess wall established the diagnosis of urethral carcinoma. In November 2005 extensive penoscrotectomy was done followed by chemo radiotherapy. But the prognosis was so bad that the patient died in November 2006. Urethral carcinoma is a rare disease diagnosed in the department of urology, Mymensingh Medical College Hospital, the prognosis of which is also poor even after extensive operations. PMID- 17344792 TI - Simultaneous occurrence of multiple types of cutaneous tuberculosis (TVC and PNT) with internal organ tuberculosis (PTB). AB - A 40 years old male patient of poor socioeconomic condition presented with a well circumscribed rough surfaced and fissured, verrucous plaque on left axilla and a similar lesion on right foot- which were clinically diagnosed as tuberculosis verrucosa cutis. He also had necrotic papular eruption with varioliform scarring in some lesions on upper back clinically diagnosed as papulonecrotic tuberculid. He had fever and cough and mild weight loss suspicious of pulmonary tuberculosis. On investigation ESR was raised, mild anaemia was present, MT was strongly positive, chest x-ray was suggestive of tuberculosis. So, he was diagnosed as a case of simultaneous occurrence of tuberculosis verrucosa cutis (TVC) with papulonecrotic tuberculid (PNT) with pulmonary tuberculosis (PTB). Standard anti tuberculosis chemotherapy already started to offer cure of all lesions. PMID- 17344793 TI - Choledochal cyst. AB - Choledochal cyst, a congenital anomaly, is a premalignant condition. Progressive damage to the bile ducts and to the liver parenchyma may also have association with the condition. Subsequent risk of developing cholangiocarcinoma may be lessen by early diagnosis and prompt definitive surgical treatment, that may even permanently correct the condition. A young lady was admitted into Mymensingh Medical College Hospital and was presented with pain in the upper abdomen associated with intermittent vomiting for several months. Her per abdominal examination revealed an ill defined mass in the epigastrium and right hypogastrium with diffuse tenderness. Patients may also present with attacks of jaundice of obstructive type, but this was absent in this particular case. Diagnosis of choledochal cyst was confirmed by the ultrasound. On exploration, the cyst was excised and Hepatico-jejunostomy and jejuno-jejunostomy was done by Roux-en-Y method. Her post operative period was uneventful and followed up till to date. Purpose of this presentation is to emphasize early diagnosis and definitive treatment of this developmental anomaly that may predispose to malignancy. PMID- 17344794 TI - Insulin analogues: new dimension of management of diabetes mellitus. AB - Insulin is one of the fundamental tools for the management of diabetes mellitus. All type 1 diabetic patients and most of the type 2 require the appropriate support of insulin for good glycemic control, long term healthy outcome and also to overcome the acute crisis. It is almost impossible to mimic the endogenous physiological insulin secretion curve by external administration of short acting human insulin and conventional intermediate acting insulin, neutral protamin Hagedorn (NPH), the so called basal insulin. Short acting human insulin has got a delayed onset of action, late peak and a long tail leading to postprandial hyperglycemia and late hypoglycemia. The so called basal insulin (NPH) is not truly a basal or peakless insulin. Its onset of action takes about 2 - 4 hours with a peak action and a tail. It can not maintain a constant basal level leading to premeal and fasting hyperglycemia and chance of hypoglycemia during peak action, particularly after night injection. To overcome the limitations of human insulin, during the last decade, three ultrashort acting and two long acting basal analogues have been developed by modifications of primary molecule of human insulin. The ultrashort acting analogue insulins are insulin lispro, insulin aspart and insulin glulisine. The basal analogues are insulin glargin and insulin detemir. The pharmacokinetic profiles of novel analogue molecules provide a better opportunity to mimic a physiological pattern of insulin administration, better glycemic control, less chance of hypoglycemia, greater flexibility and a healthy longterm outcome. PMID- 17344795 TI - RTOG 0522: a randomized phase III trial of concurrent accelerated radiation and cisplatin versus concurrent accelerated radiation, cisplatin, and cetuximab [followed by surgery for selected patients] for Stage III and IV head and neck carcinomas. PMID- 17344796 TI - What is the significance of molecular remission in multiple myeloma? AB - The present definition of complete remission (CR) in myeloma is not adequate. The definition is mainly based on measuring the secreted product of myeloma cells (M protein), which has a high interpatient and intrapatient variability, rather than on direct measurement of the remaining tumor load. Polymerase chain reaction (PCR) techniques are very sensitive to measure minimal residual disease, but in myeloma such a technique is very costly and labor intensive because a specific probe needs to be generated for each patient. There is preliminary evidence, based on a limited number of patients analyzed, that specific PCRs are better predictors of outcome in myeloma than the presently used definition of hematologic CR. Our limited experience indicates that with intensive therapy, including tandem transplants, a high percentage of patients in hematologic CR also achieve a molecular CR. The time to disease progression of such patients appears to be significantly longer compared to that of patients not achieving a molecular CR. PMID- 17344797 TI - The Development of rapamycin as an orphan drug. PMID- 17344798 TI - The current status of vaccine development in colorectal cancer. PMID- 17344799 TI - The recent advances in classic BCR-ABL-negative myeloproliferative disorders. PMID- 17344800 TI - The NCCN guidelines on venous thromboembolism. PMID- 17344801 TI - Advances in the diagnosis and treatment of malignant childhood brain tumors. PMID- 17344802 TI - Mobilization and collection of autologous hematopoietic progenitor/stem cells. AB - Autologous hematopoietic progenitor/stem cell (HPC) transplantation has become a standard treatment for a wide variety of malignancies. Most HPCs at present are collected from the peripheral blood via leukapheresis following chemotherapy and/or growth factor-mediated mobilization. Several commercial platforms are available to enumerate the circulating levels of CD34+ HPCs. These values can then be used to guide the timing of leukapheresis as well as to measure the success of daily collections. Most mobilization regimens consist of chemotherapy followed by one or more growth factors such as granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, erythropoietin, or AMD3100. Occasionally a subset of patients will prove unable to mobilize effectively enough to collect at least 2 x 106 CD34+ cells/kg, the number of HPCs currently considered to be appropriate for timely engraftment and recovery of hematopoiesis. In this subset of patients, repeat HPC collection or marrow harvest with or without growth factor stimulation may be tried. The importance of the stem cell niche in mobilization, in particular the relationship of osteoblasts and the sympathetic nervous system in the release of HPCs and other cells from the marrow stroma, may lead to entirely different or improved methods of mobilization in the future. Recent research has explored the benefits of using HPCs outside of the oncology arena, notably in the area of cardiac myocyte regeneration following infarction, making the subject of mobilization potentially important to physicians in many areas of medicine. PMID- 17344803 TI - Recent experience with decitabine in MDS. PMID- 17344804 TI - Recent degeneration of an old duplicated flowering time gene in Brassica nigra. AB - Gene and genome duplications play a major role in the evolution of plant species. The Brassica nigra genome is highly replicated as a result of ancient polyploidization events. Two copies of the flowering time gene CONSTANS (COa and COb) have been identified in B. nigra, and previous studies showed that COa is functional. In the present study, the polymorphism of 92 COb alleles sampled in seven populations was analyzed. Both polymorphism and recombination levels were elevated and varied strongly among populations and 8% of COb alleles exhibit apparently disabling mutations. Sequence data, however, do not provide unambiguous support for the presence of relaxed selective constraint on COb as compared to known functional CO genes. On the one hand, some of the disabling mutations reached high-frequency arguing for a loss of function but, on the other hand, the ratio of nonsynonymous to synonymous nucleotide polymorphism and diversity is low and similar to that observed in other B. nigra CO and CO-like genes, supporting the conservation of some function. We also showed that COb is still transcribed. Finally, the flowering time of Arabidopsis thaliana co mutant plants transformed with COb alleles with and without apparent disabling mutations was similar. We propose that COb was retained for a long period after duplication, but a recent fixation of a detrimental mutation, possibly as an effect of a bottleneck, resulted in its nonfunctionalization. We also speculate as to the presence of subsequent selection for rapid degeneration of the gene. PMID- 17344805 TI - Dos and don'ts of testing the geographic mosaic theory of coevolution. AB - The geographic mosaic theory of coevolution is stimulating much new research on interspecific interactions. We provide a guide to the fundamental components of the theory, its processes and main predictions. Our primary objectives are to clarify misconceptions regarding the geographic mosaic theory of coevolution and to describe how empiricists can test the theory rigorously. In particular, we explain why confirming the three main predicted empirical patterns (spatial variation in traits mediating interactions among species, trait mismatching among interacting species and few species-level coevolved traits) does not provide unequivocal support for the theory. We suggest that strong empirical tests of the geographic mosaic theory of coevolution should focus on its underlying processes: coevolutionary hot and cold spots, selection mosaics and trait remixing. We describe these processes and discuss potential ways each can be tested. PMID- 17344807 TI - Scanning-tunnelling spectra of cuprates. AB - The study of bosonic modes that couple to the charge carriers is a key element in understanding superconductivity. Using atomic-resolution scanning-tunnelling microscopy (STM) to extract the spectrum of these modes in the high-temperature superconductor Bi2Sr2CaCu2O(8+delta), Lee et al. find a mode whose frequency does not depend on doping but that changes on isotopic substitution of 16O with 18O. From this, they infer a role for lattice modes (phonons). However, examination of their data reveals a weaker, but distinct, feature that has all the characteristics of the magnetic excitation identified as the bosonic mode in other competing experiments. We therefore suggest that the lattice mode seen by Lee et al. is not relevant to superconductivity and is due to inelastic tunnelling through the insulating oxide layer. PMID- 17344812 TI - No more hot air. PMID- 17344806 TI - Selective induction of human hepatic cytochromes P450 2B6 and 3A4 by metamizole. AB - The pyrazolone drug metamizole is a widely used analgesic. Analysis of liver microsomes from patients treated with metamizole revealed selectively higher expression of cytochromes P450, CYP2B6 and CYP3A4 (3.8- and 2.8-fold, respectively), and 2.9-fold higher bupropion hydroxylase activity compared with untreated subjects. Further investigation of metamizole and various derivatives on different potential target genes in human primary hepatocytes demonstrated time- and concentration-dependent induction by metamizole of CYP2B6 (7.8- and 3.1 fold for mRNA and protein, respectively, at 100 muM) and CYP3A4 (2.4- and 2.9 fold, respectively), whereas other genes (CYP2C9, CYP2C19, CYP2D6, NADPH:cytochrome P450 reductase, ABCB1, constitutive androstane receptor (CAR), pregnane X receptor (PXR)) were not substantially altered. Using reporter gene assays, we show that metamizole is not acting as a direct ligand to either PXR or CAR, suggesting a phenobarbital-like mechanism of induction. These data warrant further studies to elucidate the drug-interaction potential of metamizole, especially in patients with long-term treatment. PMID- 17344811 TI - Tackling tuberculosis. PMID- 17344813 TI - The ends of the Earth. PMID- 17344815 TI - Scriptural violence can foster aggression. PMID- 17344816 TI - Western states launch carbon scheme. PMID- 17344817 TI - Our Solar System last week. PMID- 17344820 TI - Superconductivity two decades on. PMID- 17344819 TI - Biobank provides leads for selecting guide dogs. PMID- 17344821 TI - Design chosen for nuclear warheads. PMID- 17344823 TI - A place in the sun. PMID- 17344826 TI - Polar research: buried treasure. PMID- 17344827 TI - Polar research: polar year projects. PMID- 17344828 TI - Polar research: school of rock. PMID- 17344829 TI - Polar research: the new face of the Arctic. PMID- 17344830 TI - Fossils: new journal will oppose illegal trade. PMID- 17344831 TI - A Moon base offers more than just a good view. PMID- 17344832 TI - Abderhalden's fraud still wins him some supporters. PMID- 17344833 TI - Keeping faith with trial volunteers. PMID- 17344838 TI - Control without hierarchy. PMID- 17344839 TI - Cancer: drivers and passengers. PMID- 17344840 TI - Materials science: silicon life forms. PMID- 17344841 TI - Evolutionary biology: the Elvis paradox. PMID- 17344842 TI - Planetary science: water cycling on Mars. PMID- 17344844 TI - Plant biology: the force from without. PMID- 17344847 TI - An ancient nova shell around the dwarf nova Z Camelopardalis. AB - Cataclysmic variables (classical novae and dwarf novae) are binary star systems in which a red dwarf transfers hydrogen-rich matter, by way of an accretion disk, to its white dwarf companion. In dwarf novae, an instability is believed to episodically dump much of the accretion disk onto the white dwarf. The liberation of gravitational potential energy then brightens these systems by up to 100-fold every few weeks or months. Thermonuclear-powered eruptions thousands of times more luminous occur in classical novae, accompanied by significant mass ejection and formation of clearly visible shells from the ejected material. Theory predicts that the white dwarfs in all dwarf novae must eventually accrete enough mass to undergo classical nova eruptions. Here we report a shell, an order of magnitude more extended than those detected around many classical novae, surrounding the prototypical dwarf nova Z Camelopardalis. The derived shell mass matches that of classical novae, and is inconsistent with the mass expected from a dwarf nova wind or a planetary nebula. The shell observationally links the prototypical dwarf nova Z Camelopardalis with an ancient nova eruption and the classical nova process. PMID- 17344846 TI - Patterns of somatic mutation in human cancer genomes. AB - Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated. PMID- 17344848 TI - Meridiani Planum and the global hydrology of Mars. AB - The Opportunity Mars Exploration Rover found evidence for groundwater activity in the Meridiani Planum region of Mars in the form of aeolian and fluvial sediments composed of sulphate-rich grains. These sediments appear to have experienced diagenetic modification in the presence of a fluctuating water table. In addition to the extensive secondary aqueous alteration, the primary grains themselves probably derive from earlier playa evaporites. Little is known, however, about the hydrologic processes responsible for this environmental history-particularly how such extensive evaporite deposits formed in the absence of a topographic basin. Here we investigate the origin of these deposits, in the context of the global hydrology of early Mars, using numerical simulations, and demonstrate that Meridiani is one of the few regions of currently exposed ancient crust predicted to have experienced significant groundwater upwelling and evaporation. The global groundwater flow would have been driven primarily by precipitation-induced recharge and evaporative loss, with the formation of the Tharsis volcanic rise possibly playing a role through the burial of aquifers and induced global deformation. These results suggest that the deposits formed as a result of sustained groundwater upwelling and evaporation, rather than ponding within an enclosed basin. The evaporite formation coincided with a transition to more arid conditions that increased the relative impact of a deep-seated, global-scale hydrology on the surface evolution. PMID- 17344849 TI - Observation of the two-channel Kondo effect. AB - Some of the most intriguing problems in solid-state physics arise when the motion of one electron dramatically affects the motion of surrounding electrons. Traditionally, such highly correlated electron systems have been studied mainly in materials with complex transition metal chemistry. Over the past decade, researchers have learned to confine one or a few electrons within a nanometre scale semiconductor 'artificial atom', and to understand and control this simple system in detail(3). Here we combine artificial atoms to create a highly correlated electron system within a nano-engineered semiconductor structure. We tune the system in situ through a quantum phase transition between two distinct states, each a version of the Kondo state, in which a bound electron interacts with surrounding mobile electrons. The boundary between these competing Kondo states is a quantum critical point-namely, the exotic and previously elusive two channel Kondo state, in which electrons in two reservoirs are entangled through their interaction with a single localized spin. PMID- 17344850 TI - Chemical reduction of three-dimensional silica micro-assemblies into microporous silicon replicas. AB - The carbothermal reduction of silica into silicon requires the use of temperatures well above the silicon melting point (> or =2,000 degrees C). Solid silicon has recently been generated directly from silica at much lower temperatures (< or =850 degrees C) via electrochemical reduction in molten salts. However, the silicon products of such electrochemical reduction did not retain the microscale morphology of the starting silica reactants. Here we demonstrate a low-temperature (650 degrees C) magnesiothermic reduction process for converting three-dimensional nanostructured silica micro-assemblies into microporous nanocrystalline silicon replicas. The intricate nanostructured silica microshells (frustules) of diatoms (unicellular algae) were converted into co-continuous, nanocrystalline mixtures of silicon and magnesia by reaction with magnesium gas. Selective magnesia dissolution then yielded an interconnected network of silicon nanocrystals that retained the starting three-dimensional frustule morphology. The silicon replicas possessed a high specific surface area (>500 m(2) g(-1)), and contained a significant population of micropores (< or =20 A). The silicon replicas were photoluminescent, and exhibited rapid changes in impedance upon exposure to gaseous nitric oxide (suggesting a possible application in microscale gas sensing). This process enables the syntheses of microporous nanocrystalline silicon micro-assemblies with multifarious three-dimensional shapes inherited from biological or synthetic silica templates for sensor, electronic, optical or biomedical applications. PMID- 17344851 TI - Origin of avian genome size and structure in non-avian dinosaurs. AB - Avian genomes are small and streamlined compared with those of other amniotes by virtue of having fewer repetitive elements and less non-coding DNA. This condition has been suggested to represent a key adaptation for flight in birds, by reducing the metabolic costs associated with having large genome and cell sizes. However, the evolution of genome architecture in birds, or any other lineage, is difficult to study because genomic information is often absent for long-extinct relatives. Here we use a novel bayesian comparative method to show that bone-cell size correlates well with genome size in extant vertebrates, and hence use this relationship to estimate the genome sizes of 31 species of extinct dinosaur, including several species of extinct birds. Our results indicate that the small genomes typically associated with avian flight evolved in the saurischian dinosaur lineage between 230 and 250 million years ago, long before this lineage gave rise to the first birds. By comparison, ornithischian dinosaurs are inferred to have had much larger genomes, which were probably typical for ancestral Dinosauria. Using comparative genomic data, we estimate that genome wide interspersed mobile elements, a class of repetitive DNA, comprised 5-12% of the total genome size in the saurischian dinosaur lineage, but was 7-19% of total genome size in ornithischian dinosaurs, suggesting that repetitive elements became less active in the saurischian lineage. These genomic characteristics should be added to the list of attributes previously considered avian but now thought to have arisen in non-avian dinosaurs, such as feathers, pulmonary innovations, and parental care and nesting. PMID- 17344852 TI - The epidermis both drives and restricts plant shoot growth. AB - The size of an organism is genetically determined, yet how a plant or animal achieves its final size is largely unknown. The shoot of higher plants has a simple conserved body plan based on three major tissue systems: the epidermal (L1), sub-epidermal (L2) and inner ground and vascular (L3) tissues. Which tissue system drives or restricts growth has been a subject of debate for over a century. Here, we use dwarf, brassinosteroid biosynthesis and brassinosteroid response mutants in conjunction with tissue-specific expression of these components as tools to examine the role of the epidermis in shoot growth. We show that expression of the brassinosteroid receptor or a brassinosteroid biosynthetic enzyme in the epidermis, but not in the vasculature, of null mutants is sufficient to rescue their dwarf phenotypes. Brassinosteroid signalling from the epidermis is not sufficient to establish normal vascular organization. Moreover, shoot growth is restricted when brassinosteroids are depleted from the epidermis and brassinosteroids act locally within a leaf. We conclude that the epidermis both promotes and restricts shoot growth by providing a non-autonomous signal to the ground tissues. PMID- 17344853 TI - Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres. AB - Long interspersed element-1 (LINE-1 or L1) elements are abundant, non-long terminal-repeat (non-LTR) retrotransposons that comprise approximately 17% of human DNA. The average human genome contains approximately 80-100 retrotransposition-competent L1s (ref. 2), and they mobilize by a process that uses both the L1 endonuclease and reverse transcriptase, termed target-site primed reverse transcription. We have previously reported an efficient, endonuclease-independent L1 retrotransposition pathway (EN(i)) in certain Chinese hamster ovary (CHO) cell lines that are defective in the non-homologous end joining (NHEJ) pathway of DNA double-strand-break repair. Here we have characterized EN(i) retrotransposition events generated in V3 CHO cells, which are deficient in DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity and have both dysfunctional telomeres and an NHEJ defect. Notably, approximately 30% of EN(i) retrotransposition events insert in an orientation specific manner adjacent to a perfect telomere repeat (5'-TTAGGG-3'). Similar insertions were not detected among EN(i) retrotransposition events generated in controls or in XR-1 CHO cells deficient for XRCC4, an NHEJ factor that is required for DNA ligation but has no known function in telomere maintenance. Furthermore, transient expression of a dominant-negative allele of human TRF2 (also called TERF2) in XRCC4-deficient XR-1 cells, which disrupts telomere capping, enables telomere-associated EN(i) retrotransposition events. These data indicate that L1s containing a disabled endonuclease can use dysfunctional telomeres as an integration substrate. The findings highlight similarities between the mechanism of EN(i) retrotransposition and the action of telomerase, because both processes can use a 3' OH for priming reverse transcription at either internal DNA lesions or chromosome ends. Thus, we propose that EN(i) retrotransposition is an ancestral mechanism of RNA-mediated DNA repair associated with non-LTR retrotransposons that may have been used before the acquisition of an endonuclease domain. PMID- 17344855 TI - Tools for drug discovery: tools of the trade. PMID- 17344858 TI - Asteroids: spun in the sun. PMID- 17344859 TI - Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. AB - Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAX5 gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAX5 mutations resulted in reduced levels of PAX5 protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer. PMID- 17344860 TI - Strain-resolved community proteomics reveals recombining genomes of acidophilic bacteria. AB - Microbes comprise the majority of extant organisms, yet much remains to be learned about the nature and driving forces of microbial diversification. Our understanding of how microorganisms adapt and evolve can be advanced by genome wide documentation of the patterns of genetic exchange, particularly if analyses target coexisting members of natural communities. Here we use community genomic data sets to identify, with strain specificity, expressed proteins from the dominant member of a genomically uncharacterized, natural, acidophilic biofilm. Proteomics results reveal a genome shaped by recombination involving chromosomal regions of tens to hundreds of kilobases long that are derived from two closely related bacterial populations. Inter-population genetic exchange was confirmed by multilocus sequence typing of isolates and of uncultivated natural consortia. The findings suggest that exchange of large blocks of gene variants is crucial for the adaptation to specific ecological niches within the very acidic, metal-rich environment. Mass-spectrometry-based discrimination of expressed protein products that differ by as little as a single amino acid enables us to distinguish the behaviour of closely related coexisting organisms. This is important, given that microorganisms grouped together as a single species may have quite distinct roles in natural systems and their interactions might be key to ecosystem optimization. Because proteomic data simultaneously convey information about genome type and activity, strain-resolved community proteomics is an important complement to cultivation-independent genomic (metagenomic) analysis of microorganisms in the natural environment. PMID- 17344861 TI - Acceleration of the rotation of asteroid 1862 Apollo by radiation torques. AB - The anisotropic reflection and thermal re-emission of sunlight from an asteroid's surface acts as a propulsion engine. The net propulsion force (Yarkovsky effect) changes the orbital dynamics of the body at a rate that depends on its physical properties; for irregularly shaped bodies, the propulsion causes a net torque (the Yarkovsky-O'Keefe-Radzievskii-Paddack or YORP effect) that can change the object's rotation period and the direction of its rotation axis. The Yarkovsky effect has been observed directly, and there is also indirect evidence of its role in the orbital evolution of asteroids over long time intervals. So far, however, only indirect evidence exists for the YORP effect through the clustering of the directions of rotation axes in asteroid families. Here we report a change in the rotation rate of the asteroid 1862 Apollo, which is best explained by the YORP mechanism. The change is fairly large and clearly visible in photometric lightcurves, amounting to one extra rotation cycle in just 40 years even though Apollo's size is well over one kilometre. This confirms the prediction that the YORP effect plays a significant part in the dynamical evolution of asteroids. PMID- 17344862 TI - Flogging gardasil. PMID- 17344863 TI - Democratizing proteomics data. PMID- 17344864 TI - Messing with home brews. PMID- 17344865 TI - Incretin mimetics vie for slice of type 2 diabetes market. PMID- 17344866 TI - Supreme Court boosts licensees in biotech patent battles. PMID- 17344867 TI - Public sector seeks to bridge 'valley of death'. PMID- 17344868 TI - US aims to tighten rules on direct-to-consumer drug ads. PMID- 17344870 TI - Agbiotech booms in emerging nations. PMID- 17344871 TI - Negotiating the RNAi patent thicket. PMID- 17344872 TI - Two views of the emperor's new clones. PMID- 17344873 TI - Two views of the emperor's new clones. PMID- 17344874 TI - Biofuels and biocontainment. PMID- 17344875 TI - A curated compendium of phosphorylation motifs. PMID- 17344876 TI - Overhauling clinical trials. PMID- 17344877 TI - The threat from within: trade secret theft by employees. PMID- 17344878 TI - Recent patent applications in RNA interference. PMID- 17344879 TI - Sequence-activity relationships guide directed evolution. PMID- 17344880 TI - Towards quantitative analysis of proteome dynamics. PMID- 17344881 TI - Promoting angiogenesis to a fault. PMID- 17344882 TI - RNA interference has second helpings. PMID- 17344883 TI - Toll-free vaccines? PMID- 17344885 TI - A human phenome-interactome network of protein complexes implicated in genetic disorders. AB - We performed a systematic, large-scale analysis of human protein complexes comprising gene products implicated in many different categories of human disease to create a phenome-interactome network. This was done by integrating quality controlled interactions of human proteins with a validated, computationally derived phenotype similarity score, permitting identification of previously unknown complexes likely to be associated with disease. Using a phenomic ranking of protein complexes linked to human disease, we developed a Bayesian predictor that in 298 of 669 linkage intervals correctly ranks the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type 2 diabetes and coronary heart disease. Our publicly available draft of protein complexes associated with pathology comprises 506 complexes, which reveal functional relationships between disease promoting genes that will inform future experimentation. PMID- 17344886 TI - Research training and academic disciplines at the convergence of nanotechnology and biomedicine in the United States. PMID- 17344888 TI - Splenic and immune alterations of the Sparc-null mouse accompany a lack of immune response. AB - Sparc-null mice have been used as models to assess tumor-host immune cell interactions. However, it is not known if they have a competent immune system. In this study, the immune systems of Sparc wild-type and null mice were compared. Mice were assessed for differences in total body weight, spleen weight and spleen to-body weight ratios. Spleens were compared with respect to morphology, and Sparc, Ki-67, MOMA-1 and IgM expression. Immune cells in blood, bone marrow and spleen were assessed by blood smears, automated blood panel, and flow cytometry. Additionally, the ability of Sparc-null mice to respond to immune challenge was evaluated using a footpad model. The morphological and immunohistochemical results indicated that Sparc-null spleens had more white pulp, hyperproliferative B cells in the germinal centers, and decreased marginal zones. Sparc-null spleens lacked normal Sparc expression in red and white pulp, marginal zones, endothelial and sinusoidal cells. By flow analysis, B cells were decreased and T cells were increased in the bone marrow. Finally, Sparc-null mice were unable to mount an immune response following footpad lipopolysaccharide challenge. These data confirm that Sparc-null mice have an impaired immune system. PMID- 17344889 TI - Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort. AB - We evaluated the roles of five single-nucleotide polymorphisms (SNPs) within PDCD1, and haplotypes defined by these SNPs, for the development of systemic lupus erythematosus (SLE) and specific sub-phenotypes (nephritis, antiphospholipid antibody positive, arthritis and double-stranded DNA positive) within a multiethnic US cohort of 1036 patients. Family based analyses were performed using 844 simplex families from four ethnic groups (Caucasian, Asian, Hispanic and African American). Subjects were genotyped for five 'tag' SNPs (selected from 15) to provide complete genetic information in all main ethnic groups. We employed transmission disequilibrium testing to assess risk for SLE by allele or haplotype, and multiple logistic regression analysis of SLE cases to examine associations with specific sub-phenotypes. In family based analyses, a haplotype containing the PD1.3A allele was significantly associated with SLE susceptibility among Caucasian families (P=0.01). Among Hispanic families, two novel SNPs were associated with SLE risk (P=0.005 and 0.01). In multivariate logistic regression analyses, five haplotypes were associated with specific sub phenotypes among the different ethnic groups. These results suggest that PDCD1 genetic variation influences the risk and expression of SLE and that these associations vary according to ethnic background. PMID- 17344890 TI - A CD40 Kozak sequence polymorphism and susceptibility to antibody-mediated autoimmune conditions: the role of CD40 tissue-specific expression. AB - Previously, we and others have demonstrated the association of a C/T single nucleotide polymorphism (SNP), in the Kozak sequence of CD40, with Graves' disease (GD). Here, using an expanded data set of patients, we confirm the association of the CD40 SNP with GD (n=210, P=0.002, odds ratio (OR)=1.8). Subset analysis of patients with persistently elevated thyroid peroxidase (TPO) and/or thyroglobulin (Tg) antibodies (Abs), (TPO/Tg Abs), after treatment (n=126), revealed a significantly stronger association of the SNP with disease (P=5.2 x 10(-5), OR=2.5) than in GD patients who were thyroid antibody-negative. However, the CD40 SNP was not associated with TPO/Tg Abs in healthy individuals. Next, we tested the CD40 SNP for association with Myasthenia Gravis (MG), which, like GD is an antibody-mediated autoimmune condition. Analysis of 81 MG patients found no association of the SNP with disease. Functional studies revealed significant expression of CD40 mRNA and protein in the thyroid (target tissue in GD) but not in skeletal muscle (target tissue in MG). Combined, our genetic and tissue expression data suggest that the CD40 Kozak SNP is specific for thyroid antibody production involved in the etiology of GD. Increased thyroidal expression of CD40 driven by the SNP may contribute to this disease specificity. PMID- 17344892 TI - Kidney disease: wherefore, whence, and whereto? PMID- 17344893 TI - Sirolimus-associated chronic pyogenic periungual infection. PMID- 17344894 TI - Renal response to repeated exposure to endotoxin: implications for acute kidney injury. AB - Zager and colleagues demonstrate that endotoxin tolerance is accompanied by an augmented inflammatory response in the kidney, the latter also exhibiting cholesterol-dependent cytoresistance. These novel findings are discussed mainly from the perspective of acute kidney injury and its prevention by preconditioning and the elicitation of cytoprotective pathways. PMID- 17344895 TI - Renal albumin handling: a look at the dark side of the filter. AB - Renal albumin handling is of major interest because albuminuria is an important risk factor for reno-cardiovascular diseases. In this issue a challenging study attempts to shift the paradigm of very low fractional albumin filtration and degradation in proximal tubule cells. The conclusions are of great potential relevance but require urgent validation so that we gain a clearer view of the dark side of the glomerular filter. PMID- 17344896 TI - Measuring risk in end-stage renal disease: is N-terminal pro brain natriuretic peptide a useful marker? AB - Natriuretic peptides are important in the maintenance of body volume homeostasis. There has been interest in utilizing the levels of these peptides to diagnose and prognosticate cardiovascular disease. In end-stage renal disease, the diagnostic utility of these peptides is limited. Madsen et al. report that levels of N terminal pro brain natriuretic peptide (NT-proBNP) levels offer important information on the risk of mortality in patients undergoing hemodialysis. PMID- 17344898 TI - Response to 'The low-calcium concentration of dialysate induced a marked increase of serum parathyroid hormone level in a continuous ambulatory peritoneal dialysis patient'. PMID- 17344900 TI - Injection of IL-12 gene-transduced dendritic cells into mouse liver tumor lesions activates both innate and acquired immunity. AB - Dendritic cell (DC)-based vaccines have been applied clinically in the setting of advanced-stage cancer. To date, the clinical efficacy of these vaccines has been limited, possibly owing to the impairment of transferred DC function in cancer bearing patients. In this study, we examined the therapeutic efficacy of interleukin-12 (IL-12) gene-transfected DCs isolated from tumor-bearing hosts against liver tumor. The endogenous DCs isolated from subcutaneous (s.c.) CMS4 tumor-bearing mice (CMS4DC) exhibited decreased expression levels of antigen presenting molecules and low-allostimulatory capacity. CMS4DC produced less IL 12p70 than DCs isolated from normal mice. Adenoviral transfection of IL-12 gene into CMS4DC (AdIL12DC) restored the expression of antigen-presenting molecules and allostimulatory capacity. Intratumoral (i.t.) delivery of AdIL12DC resulted in complete rejection of intrahepatic CMS4 tumors and activation of innate and acquired immune cells. Antibody depletion studies revealed that both CD4(+) and CD8(+) T cells as well as natural killer cells play critical roles in mediating liver tumor rejection. I.t. treatment of AdIL12DC resulted in long-term protection against s.c. rechallenge with CMS4 tumor cells. These results revealed that IL-12 gene transfer is capable of improving the impaired functions of DC isolated from tumor-bearing hosts, and support the preclinical therapeutic efficacy of intrahepatic injection of AdIL12DC. PMID- 17344901 TI - Localized viral vector delivery to enhance in situ regenerative gene therapy. AB - A lyophilization method was developed to locally release adenoviral vectors directly from biomaterials for in situ regenerative gene therapy. Adenovirus expressing a beta-galactosidase reporter gene (AdLacZ) was mixed with different excipient formulations and lyophilized on hydroxyapatite (HA) disks followed by fibroblasts culturing and 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X gal) staining, suggesting 1 M sucrose in phosphate-buffered saline had best viability. Adenovirus release studies showed that greater than 30% virus remained on the material surface up to 16 h. Lyophilized adenovirus could be precisely localized in defined patterns and the transduction efficiency was also improved. To determine if the lyophilization formulations could preserve viral bioactivity, the lyophilized AdLacZ was tested after being stored at varying temperatures. Bioactivity of adenovirus lyophilized on HA was maintained for greater than 6 months when stored at -80 degrees C. In vivo studies were performed using an adenovirus encoding BMP-2 (AdBMP-2). AdBMP-2 was lyophilized in gelatin sponges and placed into rat critical-size calvarial defects for 5 weeks. Micro-computed tomography (micro-CT) analysis demonstrated that free-form delivery of AdBMP-2 had only modest effects on bone formation. In contrast, AdBMP-2 lyophilized in gelatin sponges led to more than 80% regeneration of critical-size calvarial defects. PMID- 17344902 TI - Adeno-associated viral gene transfer of transforming growth factor-beta1 to human mesenchymal stem cells improves cartilage repair. AB - Bone marrow cells are routinely accessed clinically for cartilage repair. This study was performed to determine whether adeno-associated virus (AAV) effectively transduces human bone marrow-derived mesenchymal stem cells (hMSC) in vitro, whether AAV infection interferes with hMSC chondrogenesis and whether AAV transforming growth factor-beta-1 (TGF-beta1)-transduced hMSC can improve cartilage repair in vivo. Adult hMSC were transduced with AAV-green fluorescent protein (GFP) or AAV-transforming growth factor beta1 (TGF beta1) and studied in pellet cultures. For in vivo studies, AAV-GFP and AAV-TGF-beta1-transduced hMSCs were implanted into osteochondral defects of 21 athymic rats. GFP was detected using fluorescent microscopy. Cartilage repair was assessed using gross and histological analysis at 4, 8 and 12 weeks. In pellet culture, GFP expression was visualized in situ through 21 days in vitro. In vivo GFP transgene expression was observed by in situ fluorescent surface imaging in 100% of GFP implanted defects at 2 , 67% at 8 and 17% at 12 weeks. Improved cartilage repair was observed in osteochondral defects implanted with AAV-TGF-beta1-transduced hMSC at 12 weeks (P=0.0047). These results show that AAV is a suitable vector for gene delivery to improve the cartilage repair potential of human mesenchymal stem cells. PMID- 17344903 TI - Nanosized bioceramic particles could function as efficient gene delivery vehicles with target specificity for the spleen. AB - We have compared the ability of several nanosized bioceramic particles including negatively charged silica (SiO(2)), neutrally charged hydroxyapatite (HA) and positively charged zirconia (ZrO(2)) nanoparticles as non-viral vectors for efficient in vivo gene delivery. A mixture of highly monodispersed aqueous suspension of HA or SiO(2) nanoparticles, coated with protamine sulfate (PS), complexed efficiently with plasmid DNA and significantly enhanced transgene expression in vitro. In comparison, ZrO(2) nanoparticles gave poor transfection efficiency under similar conditions tested. It was also determined that, under the same conditions, PS-SiO(2)-DNA, but not PS-HA-DNA-nanoplexes, were able to mediate efficient transgene expression in vitro in the presence of 50% serum. Intraperitoneal injections of PS-SiO(2)-luciferase DNA nanoplexes targeted the highest level of transgene expression in the spleen of recipient mice that lasted for more than 48 h. Injection of PS-SiO(2)-pNGVL-hFLex-MUC-1 nanoplexes was able to mediate the production of Flt-3L in the sera of recipient mice. Simultaneously, the production of Flt-3L was accompanied by the stimulation of IL 2 and interferon-gamma (IFN-gamma). Most importantly, the injection of PS-SiO(2) pNGVL-hFLex-MUC-1 nanoplexes could mount potent anti-tumour specific immune responses that led to the subsequent regression of parental tumor cells containing the muc-1 determinant. PMID- 17344904 TI - Electroporation-mediated transfer of plasmids to the lung results in reduced TLR9 signaling and inflammation. AB - Electroporation can deliver DNA efficiently and safely to tissues in live animals, including the lung where it causes little inflammation or lung injury. In contrast, cationic lipid-mediated gene transfer has been shown to induce an inflammatory response caused by unmethylated plasmid CpG residues, which activate the toll-like receptor (TLR9) signaling pathway. As TLR9 is located in the endosomal/lysosomal compartment, we hypothesized that plasmids do not activate TLR9 during electroporation because they enter the cytoplasm directly through transient pores in the plasma membrane. To test this, plasmids were transfected into kidney epithelial cells overexpressing TLR9 (HEK293-TLR9+) and cells lacking TLR9 (HEK293-TLR9-null). Interleukin (IL)-8 expression, an indicator of TLR9 activation, increased more than 10-fold at 24 h post-liposome transfection in HEK293-TLR9+ cells, but showed no significant increase in electroporated cells, compared with untransfected cells. In vivo liposome-mediated gene transfer caused increases in IL-6, IL-12, tumor necrosis factor alpha and interferon gamma in mouse bronchial alveolar lavage fluid, whereas the levels of these cytokines were more than 10-fold lower by comparison following electroporation. Depletion of alveolar macrophages suggested that this inflammatory response is mediated by resident pulmonary epithelial cells. These results suggest that electroporation mediated gene transfer bypasses the TLR-9 pathway, thus accounting for the low levels of inflammation seen with this approach. PMID- 17344905 TI - siRNA-mediated knockdown of connective tissue growth factor prevents N nitrosodimethylamine-induced hepatic fibrosis in rats. AB - Hepatic fibrosis is a dynamic process that involves the interplay of different cell types in the hepatic tissue. Connective tissue growth factor (CTGF) is a highly profibrogenic molecule and plays a crucial role in the pathogenesis of hepatic fibrosis. The aim of the present investigation was three-fold. First, we studied the expression of CTGF in the cultured hepatic stellate cells using immunohistochemical technique. Second, we induced hepatic fibrosis in rats through serial intraperitoneal injections of N-nitrosodimethylamine (NDMA; dimethylnitrosamine, DMN) and studied the upregulation of CTGF and TGF-beta1 during hepatic fibrogenesis. Third, we downregulated CTGF expression using CTGF siRNA and examined the role of CTGF siRNA to prevent the progression of NDMA induced hepatic fibrosis. The results depicted strong staining of CTGF in the transformed hepatic stellate cells in culture. Serial administrations of NDMA resulted in activation of hepatic stellate cells, upregulation of CTGF and TGF beta1 both at mRNA and protein levels and well-developed fibrosis in the liver. Immunostaining, Western blot analysis, semiquantitative and real-time RT-PCR studies showed downregulation of CTGF and TGF-beta1 after treatment with CTGF siRNA. The results of the present study demonstrated that CTGF gene silencing through siRNA reduces activation of hepatic stellate cells, prevents the upregulation of CTGF and TGF-beta1 gene expression and inhibits accumulation of connective tissue proteins in the liver. The data further suggest that knockdown of CTGF upregulation using siRNA has potential therapeutic application to prevent hepatic fibrogenesis. PMID- 17344906 TI - In vivo gene silencing in solid tumors by targeted electrically mediated siRNA delivery. AB - RNA interference (RNAi)-mediated gene silencing approaches appear very promising for therapies based on the targeted inhibition of disease-relevant genes. The major hurdle to the therapeutic development of RNAi strategies remains, however, the efficient delivery of the RNAi-inducing molecules, the short interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs), to the target tissue. With respect to cancer treatment the development of efficient delivery methods into solid tumors appears as a critical issue. However, very few studies have addressed this problem. In this study we have investigated the contribution of electrically mediated delivery of siRNA into murine tumors stably expressing an enhanced green fluorescent protein (EGFP) target reporter gene. The silencing of EGFP gene expression was quantified over time by fluorescence imaging in the living animal. Our study indicates that electric field can be used as an efficient method for siRNA delivery and associated gene silencing into cells of solid tumors in vivo. PMID- 17344907 TI - Intravascular infiltrates and organ-specific inflammation in malaria pathogenesis. AB - Malaria infects 5-10% of humanity and causes around two million deaths annually, mostly in children. The disease is of significant interest to immunologists, as acquired host immunity can limit the clinical impact of infection and partially reduces parasite replication; however, immunological reactions also contribute significantly to pathogenesis and fatalities. This review addresses the view that immunopathology in severe malaria arises predominantly from intravascular lesions resulting from a pathogen-initiated cascade of activated immune effector and regulatory cells infiltrating the vascular beds of diverse target organs, including bone marrow, spleen, brain, placenta and lungs. The main feature distinguishing these processes from classical cellular inflammation is the absence of extravasation, resulting from the intravascular location of the pathogen. Clinical and epidemiological observations combined with experimental infections in animal models suggest that parasite 'molecular patterns' or toxins cause cytokine and chemokine enhancement of infiltrates, composed of macrophages, neutrophils, natural killer (NK) cells, invariant natural killer T (iNKT) cells, gamma/delta T cells and both CD4(+) and CD8(+) effector T cells, leading to local vascular and organ derangement. Diverse pattern recognition and NK receptors crucially regulate these responding cell populations. Thus, innate immune mechanisms lie at the heart of this massive global public health problem. PMID- 17344908 TI - Acute water ingestion increases arterial blood pressure in hypertensive and normotensive subjects. AB - In patients with severe autonomic dysfunction, water ingestion elicits an acute pressor response. Hypertension may be associated with changes in cardiovascular autonomic modulation, but there is no information on the acute effects of water ingestion in patients with hypertension. In this study, we compared the effect of acute water ingestion on haemodynamic and autonomic responses of hypertensive and normotensive individuals. Eight patients with mild hypertension were compared to 10 normotensive individuals. After 30 min resting in the supine position all subjects ingested 500 ml of water. At baseline and after water ingestion, venous blood samples for plasma volume determination were collected, and electrocardiographic tracings, finger blood pressure, forearm blood flow and muscle sympathetic nerve activity (MSNA) were obtained. Water ingestion resulted in similar and minor reduction in plasma volume. Systolic and diastolic blood pressure increased in both hypertensive (mean+/-s.d.: 19/14+/-6/3 mm Hg) and normotensive subjects (17/14+/-6/3 mm Hg). There was an increase in forearm vascular resistance and in MSNA. Heart rate was reduced (hypertensive: 5+/-1 beats/min, normotensive: 5+/-6 beats/min) and the high-frequency component of heart rate and systolic blood pressure variability was increased. In hypertensive and normotensive individuals, acute water ingestion elicits a pressor response, an effect that is most likely determined by an increased vasoconstrictor sympathetic activity, and is counterbalanced by an increase in blood pressure and heart rate vagal modulation. PMID- 17344909 TI - Risk factors of peripheral arterial disease and relationship between low ankle brachial index and mortality from all-cause and cardiovascular disease in Chinese patients with hypertension. AB - The aim of this study was to evaluate the risk factors of peripheral arterial disease (PAD) and the relationship between ankle brachial index (ABI) and mortality from all-cause and cardiovascular disease (CVD) in Chinese patients with hypertension. The ABI cohort Study was designed to investigate risk factors of PAD and the relationship between ABI and mortality from all-cause and CVD in Chinese patients. ABI was identified at baseline by measuring systolic pressure at bilateral brachial and tibial arteries. Mortality surveillance was completed from November 2005 to January 2006. Among 3047 participants with hypertension at baseline, 839 (27.5%) were in the low-ABI group. Older age, female gender, higher serum level of triglycerides, lower serum level of high-density lipoprotein, a history of diabetes and a history of smoking were associated with low ABI. During the 13-month follow-up, there were 252 deaths, of which 100 died of CVD. Low ABI was associated with mortality from all-cause and CVD, whose adjusted relative risk was 1.619 (95% confidence interval 1.190-2.203) and 2.454 (1.531-3.933), respectively, in Cox regression models. The survival rate was significantly lower in the low-ABI group than in the normal-ABI group. This study demonstrated that low ABI was independently associated with a high risk of all-cause and CVD mortality in Chinese patients with hypertension. ABI should be promoted as an ideal tool to predict mortality in diabetic patients. PMID- 17344910 TI - Acute exercise-induced nitric oxide production contributes to upregulation of circulating endothelial progenitor cells in healthy subjects. AB - Exercise has been proved to promote the number and activity of circulating endothelial progenitor cells (EPCs) in humans, which contributes to improvement in endothelial function and maintenance of cardiovascular homoeostasis. However, the mechanism underlying the effect of exercise on circulating EPCs in healthy subjects is not completely understood. Here, we investigated whether the regulation of acute exercise on circulating EPCs is associated with nitric oxide (NO), vascular endothelial growth factors (VEGF) and granulocyte macrophage colony stimulating factor (GM-CSF) known to modulate circulating EPCs in healthy subjects. A total of 16 healthy male volunteers underwent a modified Bruce treadmill acute exercise protocol. The number and activity of circulating EPCs, as well as the levels of NO-VEGF and GM-CSF in plasma and culture medium before and after exercise in healthy subjects were measured. The number and activity of circulating EPCs after acute exercise were significantly higher than those before exercise in healthy subjects. In parallel, acute exercise significantly enhanced plasma NO level in healthy subjects. There is a significant linear regression relationship between the enhanced plasma NO level and increased number or activity of circulating EPCs. However, no change of plasma VEGF and GM-CSF level was observed after acute exercise. The secretion of NO-VEGF and GM-CSF by cultured EPCs remained unchanged in response to acute exercise. The present study demonstrates for the first time that acute exercise-induced NO production contributes to upregulation of circulating EPCs in healthy subjects, which suggests that NO plays an important role in the regulation of exercise on circulating EPCs. PMID- 17344911 TI - The outcome of intensive induction therapy in patients >or=70 years with acute myeloid leukemia. PMID- 17344912 TI - JAK2 V617F due to a novel TG --> CT mutation at nucleotides 1848-1849: diagnostic implication. PMID- 17344913 TI - Maintenance therapy in multiple myeloma. AB - Therapeutic advances in the treatment of multiple myeloma have significantly improved remission duration and overall survival (OS). These strategies have included the use of immunotherapy (interferon), novel agents (bortezomib, thalidomide, and lenalidomide), corticosteroids, and chemotherapy. While novel agents have had a major impact on response rates with initial therapy, most patients with multiple myeloma will eventually relapse. In the setting of minimal residual disease following standard dose or high-dose therapy, a number of different 'maintenance' strategies have emerged to prolong the duration of initial or subsequent remissions. The impact of these strategies on OS and event free survival (EFS) is critically important, as the use of ineffective maintenance therapy adds the burden of additional cost, morbidity, and may reduce quality of life. Truly successful maintenance therapy will be effective in the setting of minimal residual disease, and will improve not only EFS, but also OS. This review summarizes the currently available data in the maintenance setting for multiple myeloma, and will discuss potential future trials to further address this important issue. PMID- 17344914 TI - Telomere length of cord blood-derived CD34(+) progenitors predicts erythroid proliferative potential. AB - Excessive telomere shortening has been demonstrated in inherited and acquired blood disorders, including aplastic anemia and myelodysplastic syndromes. It is possible that replicative exhaustion, owing to critical telomere shortening in hematopoietic progenitor cells (HPCs), contributes to the development of cytopenias in these disorders. However to date, a direct link between the telomere length (TL) of human HPCs and their proliferative potential has not been demonstrated. In the present investigation, the TL and level of telomerase enzyme activity (TA) detected in cord blood (CB)-derived HPCs was found to predict erythroid expansion (P<0.01 and P=0.01 respectively). These results were corroborated by a correlation between proliferation of erythroid cells and telomere loss (P=0.01). In contrast, no correlations were found between initial TL, telomere loss or TA and the expansion of other myeloid lineage-committed cells. There was also no correlation between TL or TA and the number of clonogenic progenitors, including primitive progenitors derived from long-term culture. Our investigations revealed upregulation of telomerase to tumor cell levels in CD34- cells undergoing erythroid differentiation. Together, these results provide new insight into the regulation of TL and TA during myeloid cell expansion and demonstrate that TL is an important determinant of CB-derived erythroid cell proliferation. PMID- 17344915 TI - A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues. AB - Accumulating evidence demonstrates that adult tissues contain a population of stem cells that express early developmental markers such as stage-specific embryonic antigen and transcription factors Oct-4 and Nanog. These are the markers characteristic for embryonic stem cells, epiblast stem cells and primordial germ cells. The presence of these stem cells in adult tissues including bone marrow, epidermis, bronchial epithelium, myocardium, pancreas and testes supports the concept that adult tissues contain some population of pluripotent stem cells that is deposited in embryogenesis during early gastrulation. In this review we will discuss these data and present a hypothesis that these cells could be direct descendants of the germ lineage. The germ lineage in order to pass genes on to the next generations creates soma and thus becomes a 'mother lineage' for all somatic cell lineages present in the adult body. PMID- 17344916 TI - Expression of the JAK2 V617F mutation is not found in de novo AML and MDS but is detected in MDS-derived leukemia of megakaryoblastic nature. PMID- 17344917 TI - Fludarabine induces apoptosis of human T-cell leukemia virus type 1-infected T cells via inhibition of the nuclear factor-kappaB signal pathway. AB - Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive disease in which the human T-cell lymphotropic virus type I (HTLV-I) has been recognized as the etiologic agent. Fludarabine is a purine analog that has demonstrated significant activity in B-cell malignancies, including chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma. This study explored the effects of fludarabine on HTLV-1-infected T cells (MT-1, -2, -4 and HUT102). Fludarabine induced growth arrest and apoptosis of these cells, as measured by 3-(4,5-dimethylithiazol-2-yl) 2,5-diphenyl tetrazolium bromide assay, cell cycle analysis and annexin V staining. Moreover, exposure of HTLV-1-infected T cells to fludarabine decreased the levels of X-inhibitor of apoptosis protein in conjunction with inhibition of nuclear factor kappaB (NF-kappaB)/DNA-binding activity, as measured by Western blot analysis and electrophoretic mobility shift and reporter gene assays, respectively. Further studies found that fludarabine accumulated NF-kappaB and inhibitory subunit of NF-kappaB in cytosole in conjunction with downregulation of NF-kappaB in nucleus, suggesting that fludarabine blocked nuclear translocation of NF-kappaB. Taken together, fludarabine may be useful for treatment of individuals with ATL and other types of cancer in which NF-kappaB plays a role. PMID- 17344918 TI - Bone marrow mesenchymal stem cells are abnormal in multiple myeloma. AB - Recent literature suggested that cells of the microenvironment of tumors could be abnormal as well. To address this hypothesis in multiple myeloma (MM), we studied bone marrow mesenchymal stem cells (BMMSCs), the only long-lived cells of the bone marrow microenvironment, by gene expression profiling and phenotypic and functional studies in three groups of individuals: patients with MM, patients with monoclonal gamopathy of undefined significance (MGUS) and healthy age matched subjects. Gene expression profile independently classified the BMMSCs of these individuals in a normal and in an MM group. MGUS BMMSCs were interspersed between these two groups. Among the 145 distinct genes differentially expressed in MM and normal BMMSCs, 46% may account for a tumor-microenvironment cross-talk. Known soluble factors implicated in MM pathophysiologic features (i.e. IL (interleukin)-6, DKK1) were revealed and new ones were found which are involved in angiogenesis, osteogenic differentiation or tumor growth. In particular, GDF15 was found to induce dose-dependent growth of MOLP-6, a stromal cell-dependent myeloma cell line. Functionally, MM BMMSCs induced an overgrowth of MOLP-6, and their capacity to differentiate into an osteoblastic lineage was impaired. Thus, MM BMMSCs are abnormal and could create a very efficient niche to support the survival and proliferation of the myeloma cells. PMID- 17344919 TI - Aberrant DNA methylation of the Src kinase Hck, but not of Lyn, in Philadelphia chromosome negative acute lymphocytic leukemia. AB - Hck and Lyn are required in Philadelphia chromosome (Ph) positive acute lymphocytic leukemia (ALL). Here, we present evidence that the promoter CpG island of Hck, but not of Lyn, is aberrantly methylated in leukemia. Hck promoter DNA methylation was detected in 13 out of 23 (56.5%) hematopoietic and eight out of 10 (80%) non-hematopoietic cell lines, but not in normal controls. Treatment with 5-aza-2'-deoxycytidine induced demethylation and restoration of Hck mRNA and protein expression. Hck methylation (> or =15%) was detected in nine out of 44 (20%) patients with Ph negative ALL, and in one out 16 (6%) patients with Ph positive ALL, but not in patients with AML or chronic myelogenous leukemia. In this subset of patients, low levels of Hck methylation (10-15%) were observed in 26-30% of patients. Lyn methylation was observed in three out of 28 (10.7%) cell lines, but only in one out of 71 (1.4%) patients. Patients with Ph negative ALL and Hck methylation had a poorer prognosis. These data indicate that Hck may have tumor suppressor properties in BCR-ABL negative leukemia. PMID- 17344920 TI - Expression and mutation status of candidate kinases in multiple myeloma. PMID- 17344921 TI - Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome. AB - Activation of telomerase reverse transcriptase (hTERT) is essential for unlimited cell growth and plays a critical role in tumorigenesis. We investigated hTERT gene expression in 134 B-cell chronic lymphocytic leukemia (B-CLL) cases and evaluated its prognostic value with other prognostic markers (IgVH mutation status, CD38 and ZAP-70 expression). Real-time PCR assays to quantify either all hTERT transcripts (AT) or only the full length (FL) transcript encoding the functional protein were developed. hTERT-AT levels strongly correlated with hTERT FT levels (r=0.743, P<0.0001); both inversely correlated with the percentage of IgVH mutation (P<0.005) and were significantly higher in unmutated than in mutated cases (P=0.004 and P=0.001, respectively). The hTERT values which best discriminated between the unmutated and mutated IgVH cases were 150 and 40 copies for hTERT-AT and hTERT-FL, respectively. Using these cut-off values, there was a significant difference in the survival of patients with high or low hTERT levels (P<0.0001). Unmutated cases with low hTERT levels had an overall survival close to mutated cases with high hTERT levels. Thus, this work identifies hTERT-RNA level as a new prognostic marker in B-CLL, and may be used to identify previously unrecognized patient groups with the same IgVH mutation status and different disease outcomes. PMID- 17344922 TI - Treatment of low-risk myelodysplastic syndromes with high-dose daily oral cholecalciferol (2000-4000 IU vitamin D(3)). PMID- 17344923 TI - Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease. AB - BACKGROUND: Prolonged use of parenteral nutrition (PN) in neonates can lead to parenteral nutrition-associated liver disease (PNALD), manifested by elevated direct bilirubin concentrations, and in some cases progressing to hepatic failure. When new potential means of preventing PNALD in the neonatal intensive care unit (NICU), such as Omegaven usage, are tested in clinical trials, the studies should enroll neonates at a very high risk of developing PNALD. However, it is not always clear, in the first days of life, which neonates are most likely to develop PNALD. Therefore, preparatory to devising studies of prophylaxis against PNALD, we conducted an evaluation of all NICU patients who received PN for >or=14 day, assessing their likelihood of developing PNALD. METHODS: We performed an historic cohort analysis of all neonates in the Intermountain Healthcare system, receiving PN for 14 days or more during their stay, with dates of birth between 1 January, 2002 and 30 June, 2006. RESULTS: During the 4(1/2) year period, 9861 neonates were cared for in the Intermountain Healthcare NICUs. Of these, 9547 (96.8%) survived for at least 28 days, and of these 6543 (68.5%) received PN. Twenty-one percent (1366 patients) of those receiving PN, received it for >or=14 days. PNALD was ascertained in this group by a direct bilirubin >or=2.0 mg/dl. Neonates receiving PN for 14-28 days had a 14% incidence of PNALD, those receiving PN for 29-56 days had a 43% incidence, those receiving PN for 57 100 days had a 72% incidence and those receiving PN for >100 days had a 85% incidence. Groups of patients identifiable on the first day of life as having the highest risk of developing PNALD were birth weight <500 g (odds ratio (OR), 30.7), birth weight 500-749 g (OR, 13.1), gastrochisis (OR, 20.3) and jejunal atresia (OR, 24.0). Among 357 patients who developed PNALD, the highest direct bilirubin concentrations correlated with the highest serum alkaline phosphatase and transaminase concentrations. Deaths after 28 days were much more common in those with the highest direct bilirubin and transaminase concentrations (P<0.0001). CONCLUSIONS: In the first days of life, certain NICU patients can be identified as being at very high risk for developing PNALD. These are patients <750 g birth weight, those with gastrochisis and those with jejunal atresia. We speculate that these groups would be reasonable subjects for including in a PNALD prophylaxis trial, testing new preventative strategies such as Omegaven usage. PMID- 17344924 TI - Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis. AB - OBJECTIVES: To evaluate the accuracy of serum amyloid A (SAA), an acute phase protein in the detection of neonatal early-onset sepsis, by means of a fast automated SAA kit. STUDY DESIGN: Full-term infants <72 h of age, who had risk factors and/or were suspected of having sepsis, were eligible for study. The levels of SAA were taken at 0, 24 and 48 h post sepsis evaluation. Thirty matched infants served as a control group for comparing SAA concentrations. RESULTS: Of 104 infants eligible for entry to the study, 23 had sepsis and 81 had not sepsis. The SAA levels of the septic group were significantly higher than those of the nonseptic group at 0, 24 and 48 h (P<0.01 for all time points). In comparison with C-reactive protein (CRP), SAA levels rose earlier and in a sharper manner, had higher levels and returned faster to normal values in infants with early onset sepsis. At 0 h post-sepsis evaluation, serum SAA had an overall better diagnostic accuracy for predicting early onset sepsis than CRP (sensitivity (96 vs 30%), specificity (95 vs 98%), positive predictive value (85 vs 78%), negative predictive value (99 vs 83%), positive likelihood ratio (19 vs 12), and negative likelihood ratio (0.05 vs 0.71). CONCLUSIONS: SSA is advocated as an inflammatory marker of neonatal early-onset sepsis. PMID- 17344925 TI - Practice ordering guidance for neonatal parenteral nutrition. AB - OBJECTIVE: Neonatal parenteral nutrition (PN) is designed for very low birth weight infants (BW < or = 1500 g) for whom enteral feedings are inadequate. Evaluating the clinical practice guidance (CPG) content of printed paper order forms could provide a baseline for comparison and serve as a reference for electronic neonatal nutrition order design systems. METHODS: A scoring system for clinical practice guidance was developed and applied to nine institutions printed paper PN order forms. CPG scores were assigned as: (1) generic reminder only, (2) prompt with order entry space, (3) patient specific reminder only, (4) patient specific recommendation with order entry space. User-friendliness and form completion time were also recorded. RESULTS: The overall CPG score for the six most common PN components was 1.85+/-0.68 (mean+/-1s.d.), consistent with a generic reminder, but short of a specific nutrient dose order field. Amino acid received the highest CPG score, 2.05+/-0.64; vitamins rated the lowest. The institution of origin was an independent predictor of the CPG score. CONCLUSIONS: Paper neonatal PN order forms offer relatively little CPG. Significant form variation and format reflects the need to standardize neonatal PN design as the neonatal PN design moves from paper to electronic ordering systems. PMID- 17344927 TI - Retrospective diagnosis of fatal BP180-deficient non-Herlitz junctional epidermolysis bullosa suggested by immunofluorescence (IF) antigen-mapping of parental carriers bearing enamel defects. PMID- 17344928 TI - Regulation of MMP-2 gene transcription in dermal wounds. AB - Matrix metalloproteinase-2 (MMP-2, gelatinase A) plays an essential role in angiogenesis, inflammation, and fibrosis. These processes are critical for wound healing and accordingly elevated levels of MMP-2 expression have been detected after skin injury. Our goal was to investigate the transcriptional activation of the MMP-2 gene in a model of skin injury by using two different MMP-2/LacZ reporter mice. Upon skin injury MMP-2 expression was upregulated, whereas tissue from normal skin stained negative except for occasional macrophages, sweat glands, and hair follicles. Skin injury also activated MMP-2 proteolytic activity and reporter gene expression. We demonstrate that MMP-2 regulatory sequences 1686/+423 drive appropriate injury-induced MMP-2-promoter activation. Reporter gene expression was predominantly detectable in endothelial cells and in macrophages. Deletion of the 5' responsive element, denoted RE-1, residing at 1241/+423 bp of the regulatory sequence led to abrogated MMP-2 transcription in vivo. The findings define a crucial role for the enhancer element RE-1 in injury induced MMP-2 transcription of the skin. PMID- 17344929 TI - Sun-protective behaviors in families at increased risk of melanoma. AB - The aim of this study was to compare reported behavior in the sun in melanoma families with that of geographical healthy controls and to determine the predictors of that behavior to inform the process of counseling melanoma families. One hundred and seventy individuals with a family history of melanoma and 140 controls completed a postal questionnaire. Thirty-one percent of relatives reported sunburn in the previous summer, compared with 41% of controls. Fifty-five percent of relatives had acquired a suntan so that adherence to health education advice was disappointing. Male relatives were particularly likely to report sunburn. Higher knowledge scores correlated well with greater belief in ability to prevent melanoma, less desire for a tan, and more protective behaviors in relatives only (not in controls). We have shown that some psychological characteristics, sex, and age have an effect on behavior, so that the educational approaches needed will vary. "Better" behaviors were reported by melanoma cases than other relatives and by members of families with larger numbers of cases, which suggests that a belief that an individual is at particular risk of melanoma is important for compliance with preventive behaviors. PMID- 17344930 TI - Requirement of dynactin p150(Glued) subunit for the functional integrity of the keratinocyte microparasol. AB - The keratinocyte microparasol, composed of a perinuclear microtubular/melano phagolysosomal complex, protects the nucleus from UV-induced DNA damage. We have previously demonstrated that cytoplasmic dynein is the motor involved in the perinuclear-directed aggregation of phagocytosed melanosomes. Dynactin, of which p150(Glued) is the major subunit, can link directly to microtubules and links organelles to dynein at different domains. To further define the mechanism of the microparasol, we transfected siRNA targeted against p150(Glued) into human keratinocytes cultured with 0.5 mm fluorescent microspheres and performed time lapse analysis, confocal immunolocalization, and Western immunoblotting after 24 and 48 hours. Western blots revealed a significant knockdown of the p150(Glued) subunit. The knockdown decreased p150(Glued) colocalization with microtubules and decreased perinuclear positioning of the convergent microtubular framework. It also inhibited perinuclear aggregation of phagocytosed fluorescent microspheres and reduced mean centripetal microsphere displacement. The findings provide evidence that dynactin p150(Glued) plays an important role in the functional integrity of the keratinocyte microparasol. PMID- 17344931 TI - Molecular analysis of DNA polymerase eta gene in Japanese patients diagnosed as xeroderma pigmentosum variant type. AB - POLH mutations were identified in 16 Japanese patients, who were diagnosed, both clinically and at a cellular level, as being of the xeroderma pigmentosum variant type (XPV). While all the patients developed skin cancer with an average onset of the cancer at 45 years, in non-XP Japanese the onset was at over 70 years. All the cell strains from the patients were normal or slightly hypersensitive to UV and most of these showed enhanced UV sensitivity when the post-UV colony formation was performed in the presence of caffeine. Immunoprecipitation analysis with two kinds of anti-POLH protein antibodies revealed that cells from 13 patients did not show the 83 kDa POLH band and that cells from one patient had a faint 83 kDa band. All of these 14 cell strains, without a POLH band or with a weak POLH band, had mutations in the POLH gene. The IP analysis of the POLH protein revealed a very useful method for screening the patients suspected of XPV. Seven mutations in the POLH gene including three novel mutations were identified. Among the mutations detected, 11 alleles out of 28 (39%) were G490T mutations. PMID- 17344932 TI - Confirmation of psoriasis susceptibility loci on chromosome 6p21 and 20p13 in French families. AB - Plaque psoriasis is a chronic inflammatory disorder of the skin. It is inherited as a multifactorial trait, with a strong genetic component. Linkage studies have identified a large number of disease loci, but very few could be replicated in independent family sets. In this study, we present the results of a genome-wide scan carried out in 14 French extended families. Candidate regions were then tested in a second set of 32 families. Analysis of the pooled samples confirmed linkage to chromosomes 6p21 (Z(MLB) score=3.5, P=0.0002) and 20p13 (Z(MLB) score=2.9, P=0.002), although there was little contribution of the second family set to the 20p13 linkage signal. Moreover, we identified four additional loci potentially linked to psoriasis. The major histocompatibility complex region on 6p21 is a major susceptibility locus, referred to as PSORS1, which has been found in most of the studies published to date. The 20p13 locus segregates independently of PSORS1 in psoriasis families. It has previously been thought to be involved in the predisposition to psoriasis and other inflammatory disorders such as atopic dermatitis (AD) and asthma. Although psoriasis and AD rarely occur together, this reinforces the hypothesis that psoriasis is influenced by genes with general effects on inflammation and immunity. PMID- 17344933 TI - Upregulation of cytokine expression in fibroblasts exposed to loxosceles sphingomyelinase D: what is the trigger? PMID- 17344934 TI - Increased blood levels of IgG reactive with secreted Streptococcus pyogenes proteins in chronic plaque psoriasis. AB - A pathogenic role for Streptococcus (S) pyogenes infections in chronic plaque psoriasis is suspected but poorly defined. We separated cellular and supernatant proteins from S. pyogenes cultures by high-resolution two-dimensional gel electrophoresis, and used immunoblotting to demonstrate the diversity of serum or plasma IgGs that react with elements of the proteome of this bacterium. We have shown that a substantial proportion of IgG-reactive proteins from cultured S. pyogenes are secreted. The total secreted protein fraction, including diverse IgG binding elements, was subsequently used in an ELISA to measure blood titers of reactive IgG. This ELISA showed that blood samples from patients with chronic plaque psoriasis contained significantly higher titers of reactive IgG than samples from age- and sex-matched healthy controls (P=0.0009). In contrast, neither a standard assay measuring antistreptolysin O titers nor ELISAs measuring titers of IgG reactive with protein fractions from Staphylococcus aureus and Staphylococcus epidermidis, were able to distinguish between blood samples from the two groups. These findings justify the hypothesis that S. pyogenes infections are more important in the pathogenesis of chronic plaque psoriasis than has previously been recognized, and indicate the need for further controlled therapeutic trials of antibacterial measures in this common skin disease. PMID- 17344935 TI - Korean Translation of the AANCART Questionnaire. AB - The project described herein is the preparation of a culturally and linguistically appropriate Korean version of a core questionnaire developed by the Asian American Network for Cancer Awareness, Research and Training. This version will assist in the design of interventions related to cancer for the Korean American population in the future. Following an extensive literature search, procedures recommended by various studies were incorporated into the translation process. Two final Korean versions were pilot tested to evaluate which way of asking a particular question was better, as perceived by respondents. The findings from this project helped enhance the linguistic and cultural competencies in both instruments. A cognitive walk-through interview achieved by probing after each question led respondents to offer feedback about the questions, resulting in a further review and revision of the questionnaire. The next step will be to administer the final Korean version of the two instruments to a large random sample. PMID- 17344936 TI - A Cancer Pioneer's Personal and Professional Journey: A Korean American Cancer Researcher Discusses His Life's Journey and the Passion That Spurred His Success. PMID- 17344937 TI - The Birth of Korean American Cancer Control. PMID- 17344938 TI - Genetic polymorphisms of the urea transporter gene are associated with antihypertensive response to nifedipine GITS. AB - Nifedipine GITS has diuretic and natriuretic properties, which may enhance its antihypertensive efficacy. We assessed contributions of polymorphisms in the urea transporter-A gene (SLC14A2) to interindividual variations in blood pressure (BP) response to nifedipine treatment. 405 subjects from a single Chinese county received a single oral dose of 30 mg nifedipine GITS (gastrointestinal therapeutic system) daily for 16 days. We genotyped two SNPs in SLC14A2 and found significant associations for the Val227Ile (rs1123617) and Ala357Thr (rs3745009) polymorphisms with BP response to nifedipine treatment. After treatment, subjects with either Ala357/Thr357 or Thr357/Thr357 genotypes had significantly smaller mean changes in systolic BP (SBP) (beta +/- SE = -2.87 +/- 1.24 mmHg, p = 0.020) and diastolic BP (DBP) (beta +/- SE = -1.69 +/- 0.62 mmHg, p = 0.006) compared to those with the Ala357/Ala357 genotype. Subjects with either Val227/Ile227 or Ile227/Ile227 genotypes had significantly larger mean changes in SBP (beta +/- SE = 3.13 +/- 1.19, p = 0.009) and DBP (beta +/- SE = 1.50 +/- 0.60 mmHg, p = 0.013) compared with those with the Val227/Val227 genotype after treatment. Subjects carrying both the Ala357/Ala357 genotype in the Ala357Thr polymorphism and either Val227/Ile227 or Ile227/Ile227 genotypes in the Val227Ile polymorphism had the highest mean change in SBP and DBP. Our study supports the conclusion that polymorphisms in the SLC14A2 gene can predict the antihypertensive efficacy of nifedipine GITS. PMID- 17344939 TI - Evaluation of the modulatory role of nimodipine in seizures induced by kainic acid and pentylenetetrazole in mice. AB - The present study aimed at establishing the CD50 and CD99 doses along with complete dose-response profile of two convulsants, namely, kainic acid and pentylenetetrazole (PTZ), in mice and evaluating the modulatory role of the cerebroselective dihydropyridine calcium channel blocker nimodipine. Kainic acid and PTZ were administered intraperitoneally in a dose range of 1-30 mg kg(-1) and 35-75 mg kg(-1), respectively. Nimodipine was administered in graded doses (1-8 mg kg(-1), i.p.) with 15 min pretreatment time against CD99 doses of both kainic acid and PTZ. The effect of nimodipine in treated groups was compared with that of vehicle in control group. The CD50 and CD99 doses for kainic acid was found to be 2.5 and 7.5 mg kg(-1), while those of PTZ were found to be 50 and 75 mg kg( 1), respectively. Pretreatment with nimodipine inhibited seizures in a dose dependent manner, in terms of both percentage of positive responders and seizure scores against CD99 doses of both kainic acid and PTZ. The results established the protective efficacy of nimodipine against both kainic acid and PTZ-induced seizures, suggesting the role of calcium ion as a common mediator for both the types of seizures. However, further studies are necessary to ascertain the exact molecular mechanism of nimodipine. PMID- 17344940 TI - Possible neuroprotective mechanisms of curcumin in attenuating 3-nitropropionic acid-induced neurotoxicity. AB - 3-Nitropropionic acid (3-NP) is a well known fungic toxin causing neurotoxicity. Systemic administration of 3-NP causes motor and cognitive deficits that are associated with excessive free radical generation. Recently, curcumin has been implicated as a neuroprotectant in the treatment of various neurological disorders. The present study was designed to investigate the effects of curcumin in 3-NP-induced cognitive impairment and oxidative stress in rats. Curcumin, a potent antioxidant of dietary polyphenol, containing a standardized extract of Curcuma longa root (Zingiberaceae), has been reported to possess free radical scavenging, iron chelating and antiinflammatory activities. Intraperitoneal administration of 3-NP (20 mg/kg for 4 days) showed loss in body weight, declined motor function, poor retention of memory and changes in oxidative stress (lipid peroxidation, reduced glutathione and nitrite level) parameters in brain. Chronic treatment with curcumin (10, 20 and 50 mg/kg, p.o.) once daily for a period of 8 days beginning 4 days prior to 3-NP administration dose-dependently improved the 3-NP-induced motor and cognitive impairment. Biochemical analysis revealed that curcumin administration significantly attenuated 3-NP-induced oxidative stress (lipid peroxidation estimation, reduced glutathione and nitrite activity) in the brains of rats. It also significantly restored the decreased succinate dehydrogenase activity. The results of the present study clearly indicate that curcumin by its antioxidant activity showed neuroprotection against 3-NP-induced behavioral and biochemical alteration. PMID- 17344941 TI - Differential alteration of drug-metabolizing enzyme activities after cyclophosphamide/adriamycin administration in breast cancer patients. AB - Cyclophosphamide (CPA) and adriamycin (ADR) are widely used drugs for cancer chemotherapy. It has been reported that CPA and ADR singly or in combination could alter activities of a variety of drug-metabolizing enzymes in animals via multiple mechanisms. However, the effects of CPA/ADR on drug metabolism are largely unknown in human beings. Losartan metabolism has been suggested as a marker for determination of CYP2C9 activity. Caffeine is a commonly used probe to assess the metabolic activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO). The present study was designed to analyze the effects of CPA/ADR on these drug-metabolizing enzymes by using losartan and caffeine as probe drugs. A single oral dose of 25 mg losartan and a cup of instant coffee was given to 15 breast cancer patients on three occasions (before, and 2-4 h and 3 weeks after the adjuvant CPA/ADR chemotherapy [600 mg CPA/m2/day, 60 mg ADR/m2/day]). Losartan, caffeine and their metabolites were analyzed by using high-pressure liquid chromatography. When compared with baseline, CYP1A2 activity was increased by 20% and CYP2C9 activity was decreased by 315% 3 weeks after the administration of CPA/ADR chemotherapy (p = 0.05). The chemotherapy did not change the activities of CYP2A6, NAT2 or XO. CPA/ADR treatment caused a differential effect on drug-metabolizing enzyme activities, and this may contribute to predicting the efficacy and toxicity of chemotherapeutics, as well as understanding the drug-drug interactions. PMID- 17344942 TI - Calcium and survivin are involved in the induction of apoptosis by dihydroartemisinin in human lung cancer SPC-A-1 cells. AB - Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua, is an effective novel antimalarial drug. Recent studies suggest that it also has anticancer effects. The present study investigated the apoptosis activity of DHA in cultured human lung cancer cells by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay and flow cytometry. Intracellular free calcium concentrations in the lung cancer cells were evaluated by laser scanning confocal microscopy using Fura-3/AM as probe. The observations also indicated that DHA downregulated the mRNA and protein expression level of survivin in the lung cancer cell line SPC-A-1 cells, whereas it did not affect those of caspase-4. These results demonstrated that DHA can induce apoptosis of lung cancer cell line SPC-A-1 cells and that calcium and survivin participated in the apoptotic signalling pathways. PMID- 17344943 TI - Mesenteric ischemia/reperfusion-induced intestinal and vascular damage: effect of stobadine. AB - This study examined the effects of the pyridoindole compound stobadine on intestinal and vascular injury following mesenteric ischemia/reperfusion (I/R) in rats. Ischemia was induced by occlusion of the superior mesenteric artery (SMA) for 60 min, followed by 30 min reperfusion. To characterize gut impairment, some parameters of intestinal damage and biochemical variables, such as GSH content, activity of a lysosomal enzyme N-acetyl-beta-D-glucuronidase and activity of gamma-glutamyl transpeptidase, were determined. Vascular I/R-induced damage was evaluated as changes in acetylcholine evoked relaxation of mesenteric artery rings under isometric conditions. A method of amplified chemiluminescence (CL) was used to detect production of reactive oxygen species (ROS). Following I/R, pronounced intestinal injury of various intensities was observed, with maximal changes occurring in the terminal ileum. The effect of I/R was expressed mainly as increased vascular permeability, with protein leakage and subsequent hemorrhagic injury of the intestine as well as impaired endothelium-dependent SMA relaxation. Vessel dysfunction was manifested by a decrease of the maximal relaxation response to acetylcholine. An increase of CL, indicative of increased ROS production, was observed in both intestinal and vascular tissue. A novel antioxidant, stobadine, was found to reduce the increased vascular permeability and the extent of small intestine injury caused by I/R, to improve biochemical alterations accompanying I/R, to protect endothelial-dependent relaxation of mesenteric arteries, and to attenuate the CL response. The observed beneficial effect of stobadine indicates its possible application in the preventive and/or therapeutic approach to I/R-induced pathologies. PMID- 17344944 TI - Effects of methylphenidate on leptin and appetite in children with attention deficit hyperactivity disorder: an open label trial. AB - Appetite suppression is one of the most common side effects of methylphenidate (MPH), which is used for treatment of attention-deficit hyperactivity disorder (ADHD). Relation of appetite and leptin is well known but there is no report regarding MPH use and leptin. In this study we compared the baseline leptin levels of ADHD children with the controls and studied the interaction between MPH and leptin-insulin level in ADHD children under MPH treatment. The major finding of this study is that at a total daily dose of 0.6 mg/kg short-acting MPH treatment, one does not observe significant side effects related to appetite suppression and metabolic features as measured via body mass index, insulin and leptin levels. Thus this range seems to be safe in developing ADHD children with minimum side effects regarding appetite for short-term treatment. PMID- 17344945 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 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 issues focuses on the following selection of drugs: 4'-Thio-ara-C, 5 methyltetrahydrofolate; ABT-089, AD-237, AF-37702, alvocidib hydrochloride, apricitabine, armodafinil, atrasentan, AVE-5883, avian influenza vaccine, azimilide hydrochloride; Banoxantrone, BIBF-1120; CD34+ cells, certolizumab pegol, CHIR-258, cilansetron, CoFactor, CX-3543, cystemustine; D-003, dexloxiglumide, DMXB-anabaseine; Ecogramostim, elcometrine, elcometrine/ethinylestradiol, etravirine; Fenretinide, fingolimod hydrochloride, fospropofol disodium; Gaboxadol, gestodene, glutamine; Human insulin, hyaluronic acid; Incyclinide, indacaterol, ispronicline, istradefylline; Labradimil, lamifiban, lapatinib, L-arginine hydrochloride, liposomal cisplatin, liposome encapsulated paclitaxel, LY-517717; Manidipine hydrochloride/delapril hydrochloride, maraviroc, MBP(82-98), MD-0727, MDX-214, melanotan I, MMR vaccine; Nacystelyn, nalfurafine hydrochloride, nibentan, nilotinib, NK-105; OBI-1, oblimersen sodium, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, oregovomab; Pexelizumab, PG-116800, PG-CPT, PHA 794428, prasugrel; RC-3095, rDNA insulin, RFB4(dsFv)-PE38, rhEndostatin, rhenium Re-186 etidronate, rhGM-CSF, roflumilast, romidepsin; Sarcosine, SGLU1, SGN-40, succinobucol; TAU, teduglutide, telatinib, tesofensine, tipifarnib, tirapazamine, TKA-731, tolvaptan, trabectedin; Vaccimel, vatalanib succinate, velafermin, vildagliptin, vinflunine; XP-19986; YM-155. PMID- 17344947 TI - Effects of moisture damage and renovation on microbial conditions and pupils' health in two schools--a longitudinal analysis of five years. AB - Airborne microbes and pupils' symptoms were monitored in a moisture-damaged (index) school and a reference school for five consecutive years. These surveys were carried out in two separate years before the renovation of the index school, during the renovation, and one and two years after the renovation. Microbial concentrations were higher in the index school than those in the reference school before and during renovation, but afterwards, the levels decreased to the level of the reference school. The effect of remediation was seen as an altered mycobiota in the index school. Year-to-year variation of microbial concentrations, probably due to climatic factors, caused a peak in both schools but their difference remained. Several symptoms were more prevalent in the moisture-damaged school than in the reference school, but the differences disappeared during the renovations. These results emphasize the importance of using a reference building in assessing the microbial conditions of a moisture damaged building. Furthermore, microbial concentrations reflected well the technical condition of the construction, but the reported symptoms of the occupants did not strictly follow the timely fluctuation in microbial conditions. PMID- 17344948 TI - Henry's Law constants or air to water partition coefficients for 1,3,5-triazines by an LFER method. AB - Solvation descriptors have been obtained for 19 substituted 1,3,5-triazines, using literature data on water to solvent partitions, and our own experimental determinations of water to solvent partition coefficients and micellar electrokinetic chromatography (MEKC) retention factors. The solvation descriptors can then be used to predict environmentally important air to water partition coefficients, K(w), which are the reciprocal of Henry's Law constants, with due regard to units. For this class of chemistry it is shown that the values of log K(w) so obtained are generally in good agreement with the experimental values compiled in this work and also compare well with the calculated values from the established bond contribution method of Meylan and Howard as implemented in the EPI Suite, but not with calculated values from the semi-empirical quantum chemical solvation models, SM2 and SM3, recently reported by Delgado and Alderete (J. Chem. Inf. Comput. Sci., 2003, 41, 1226-1230). PMID- 17344949 TI - Volatile organic compounds (VOCs) emitted from materials collected from buildings affected by microorganisms. AB - In this study mould damaged materials, including carpet, concrete, gypsum board, insulation, plastic, sand and wood, from 20 different buildings with moisture problems were collected. To study emissions from these materials both conventional methods for sampling, such as collection on Tenax TA, were used as well as complementary methods for sampling a wider spectrum of compounds, such as more volatile VOCs, amines and aldehydes. Analysis was carried out using gas chromatography and high-performance liquid chromatography. Mass spectrometry was used for identification of compounds. Alcohols and ketones were almost exclusively emitted from the materials after they had been wet for a week. Acids were also emitted in large quantities from wet gypsum board and plastic. No primary or secondary amines could be identified, but two tertiary amines, trimethylamine and triethylamine, were emitted from sand contaminated by Bacillus. The most common moulds found were Penicillium and Aspergillus. A multivariate method (partial least squares, PLS) was used to investigate the emission patterns from the materials. Materials with bacterial growth had a different VOC profile to those with only mould growth. PMID- 17344950 TI - A land use regression model for predicting ambient fine particulate matter across Los Angeles, CA. AB - Land use regression (LUR) models have been used successfully for predicting local variation in traffic pollution, but few studies have explored this method for deriving fine particle exposure surfaces. The primary purpose of this method is to develop a LUR model for predicting fine particle or PM(2.5) mass over the five county metropolitan statistical area (MSA) of Los Angeles. PM(2.5) includes all particles with diameter less than or equal to 2.5 microns. In the Los Angeles MSA, 23 monitors of PM(2.5) were available in the year 2000. This study uses GIS to integrate data regarding land use, transportation and physical geography to derive a PM(2.5) dataset covering Los Angeles. Multiple linear regression was used to create the model for predicting the PM(2.5) surface. Our parsimonious model explained 69% of the variance in PM(2.5) with three predictors: (1) traffic density within 300 m, (2) industrial land area within 5000 m, and (3) government land area within 5000 m of the monitoring site. These results suggest the LUR method can refine exposure models for epidemiologic studies in a North American context. PMID- 17344952 TI - Challenges in the application of conventional PCB quantitation methods to studies of "invasive" freshwater organisms. AB - We describe significant and unexpected errors in application of a conventional method for the quantitative determination of polychlorinated biphenyls (PCBs) in unusual biological tissue samples. A standard method based upon microwave assisted extraction (MAE) and gas chromatography tandem mass spectrometry (GC MS/MS) was applied to a variety of "invasive" freshwater organisms, representing a variety of genera. The 12 "co-planar" PCBs (co-PCBs) were determined at ng g( 1) levels in small samples (ca. 750-1000 mg) of eight freshwater species (n = 172). We found that the conventional method could lead to random and relatively large changes in retention times. A nearly five-fold increase in retention variability was observed for "lower" organisms compared to that observed in the analysis of predatory fish tissue. These unexpected retention time changes would result in misidentifications, and become problematic not only for non-selective detectors such as electron capture but also for MS-based approaches. That is, for electron impact (EI) ionization methods, molecular ions (M(+)) are produced by loss of Cl not only for congeners in the same homolog class but also for fragments of higher homologs (e.g. M - 35 and M - 37), thereby yielding false positive measurement of the target congener when the retention time windows overlap. PMID- 17344951 TI - Occupational exposure to NDMA and NMor in the European rubber industry. AB - Many nitrosamines are suspected of being human carcinogens, with the highest concentrations in the environment being measured in the rubber industry. Time trends of personal exposure to N-nitrosodimethylamine (NDMA) and to N nitrosomorpholine (NMor) during the past two decades in the German rubber industry were analysed and compared with cross-sectional studies in the same period in the Netherlands, Poland, the UK and Sweden. In the majority of the surveyed departments exposures reduced over time, but considerable heterogeneity was present between departments and sectors. Significant reductions were primarily found in curing and post-treating departments and ranged from -3% year( 1) to -19% year(-1). In contrast, NDMA levels increased (+13% year(-1)) in maintenance and engineering in the tyres industry. Average NDMA-levels in general rubber goods (GRG) and NMor-levels in tyre production in Germany did not decrease significantly in the past two decades, whereas NDMA-levels in tyre production ( 10% year(-1)) and NMor-levels in GRG (-7% year(-1)) declined significantly after the introduction of an exposure limit for total nitrosamines in Germany in 1988. Confidence intervals of average exposures in other studied countries largely overlap trends observed in Germany. Exposure to N-nitrosamines decreased on average two-to-five fold in the German rubber industry with comparable concentration levels in other European countries. Although average levels are well below the current limits exposure has not been eliminated, and incidental high exposures do still occur. PMID- 17344953 TI - Estimating contaminant attenuation half-lives in alluvial groundwater systems. AB - One aspect of describing contamination in an alluvial aquifer is estimating changes in concentrations over time. A variety of statistical methods are available for assessing trends in contaminant concentrations. We present a method that extends trend analysis to include estimating the coefficients for the exponential decay equation and calculating contaminant attenuation half-lives. The conceptual model for this approach assumes that the rate of decline is proportional to the contaminant concentration in an aquifer. Consequently, the amount of time to remove a unit quantity of the contaminant inventory from an aquifer lengthens as the concentration decreases. Support for this conceptual model is demonstrated empirically with log-transformed time series of contaminant data. Equations are provided for calculating system attenuation half-lives for non-radioactive contaminants. For radioactive contaminants, the system attenuation half-life is partitioned into the intrinsic radioactive decay and the concentration reduction caused by aquifer processes. Examples are presented that provide the details of this approach. In addition to gaining an understanding of aquifer characteristics and changes in constituent concentrations, this method can be used to assess compliance with regulatory standards and to estimate the time to compliance when natural attenuation is being considered as a remediation strategy. A special application of this method is also provided that estimates the half-life of the residence time for groundwater in the aquifer by estimating the half life for a conservative contaminant that is no longer being released into the aquifer. Finally, the ratio of the half-life for groundwater residence time to the attenuation half-life for a contaminant is discussed as a system scale retardation factor which can be used in analytical and numerical modeling. PMID- 17344954 TI - Air pollutants and the characterization of the organic content of aerosol particles in a mixed industrial/semi-rural area in central Italy. AB - Both regulated and unregulated air pollutants were detected during an intensive seasonal sampling campaign in a mixed industrial/semi-rural area on the outskirts of Rome, Italy, at two sites located opposite a hospital waste incinerator, downwind according to the direction of the prevailing local winds. Concentrations of pollutants were significantly lower than in urban atmospheres. The composition of particulate organic material indicated a heavy biogenic impact, accompanied by a lower contribution from petroleum-related processes. Both PAH and nitro-PAH group compositions of particulates were used to assess the nature and relative importance of sources. Both sites showed that different and diffuse sources contributed to local pollution with a significant contribution from traffic, proving that the hospital waste incinerator was not the main pollution source in this area. Among unregulated compounds, a series of positional isomers of nitro PAHs and other organic compounds associated with particulate matter were investigated. In particular, 1- and 3-nitrophenanthrene identification was carried out, and they proved to be the most abundant nitro-PAHs. PMID- 17344958 TI - Environmental effects of ozone depletion: 2006 assessment: interactions of ozone depletion and climate change. Executive summary. PMID- 17344959 TI - Changes in biologically-active ultraviolet radiation reaching the Earth's surface. AB - The Montreal Protocol is working. Concentrations of major ozone-depleting substances in the atmosphere are now decreasing, and the decline in total column amounts seen in the 1980s and 1990s at mid-latitudes has not continued. In polar regions, there is much greater natural variability. Each spring, large ozone holes continue to occur in Antarctica and less severe regions of depleted ozone continue to occur in the Arctic. There is evidence that some of these changes are driven by changes in atmospheric circulation rather than being solely attributable to reductions in ozone-depleting substances, which may indicate a linkage to climate change. Global ozone is still lower than in the 1970s and a return to that state is not expected for several decades. As changes in ozone impinge directly on UV radiation, elevated UV radiation due to reduced ozone is expected to continue over that period. Long-term changes in UV-B due to ozone depletion are difficult to verify through direct measurement, but there is strong evidence that UV-B irradiance increased over the period of ozone depletion. At unpolluted sites in the southern hemisphere, there is some evidence that UV-B irradiance has diminished since the late 1990s. The availability and temporal extent of UV data have improved, and we are now able to evaluate the changes in recent times compared with those estimated since the late 1920s, when ozone measurements first became available. The increases in UV-B irradiance over the latter part of the 20th century have been larger than the natural variability. There is increased evidence that aerosols have a larger effect on surface UV-B radiation than previously thought. At some sites in the Northern Hemisphere, UV-B irradiance may continue to increase because of continuing reductions in aerosol extinctions since the 1990s. Interactions between ozone depletion and climate change are complex and can be mediated through changes in chemistry, radiation, and atmospheric circulation patterns. The changes can be in both directions: ozone changes can affect climate, and climate change can affect ozone. The observational evidence suggests that stratospheric ozone (and therefore UV-B) has responded relatively quickly to changes in ozone-depleting substances, implying that climate interactions have not delayed this process. Model calculations predict that at mid-latitudes a return of ozone to pre-1980 levels is expected by the mid 21st century. However, it may take a decade or two longer in polar regions. Climate change can also affect UV radiation through changes in cloudiness and albedo, without involving ozone and since temperature changes over the 21st century are likely to be about 5 times greater than in the past century. This is likely to have significant effects on future cloud, aerosol and surface reflectivity. Consequently, unless strong mitigation measures are undertaken with respect to climate change, profound effects on the biosphere and on the solar UV radiation received at the Earth's surface can be anticipated. The future remains uncertain. Ozone is expected to increase slowly over the decades ahead, but it is not known whether ozone will return to higher levels, or lower levels, than those present prior to the onset of ozone depletion in the 1970s. There is even greater uncertainty about future UV radiation, since it will be additionally influenced by changes in aerosols and clouds. PMID- 17344960 TI - The effects on human health from stratospheric ozone depletion and its interactions with climate change. AB - Ozone depletion leads to an increase in the ultraviolet-B (UV-B) component (280 315 nm) of solar ultraviolet radiation (UVR) reaching the surface of the Earth with important consequences for human health. Solar UVR has many harmful and some beneficial effects on individuals and, in this review, information mainly published since the previous report in 2003 (F. R. de Gruijl, J. Longstreth, M. Norval, A. P. Cullen, H. Slaper, M. L. Kripke, Y. Takizawa and J. C. van der Leun, Photochem. Photobiol. Sci., 2003, 2, pp. 16-28) is discussed. The eye is exposed directly to sunlight and this can result in acute or long-term damage. Studying how UV-B interacts with the surface and internal structures of the eye has led to a further understanding of the location and pathogenesis of a number of ocular diseases, including pterygium and cataract. The skin is also exposed directly to solar UVR, and the development of skin cancer is the main adverse health outcome of excessive UVR exposure. Skin cancer is the most common form of malignancy amongst fair-skinned people, and its incidence has increased markedly in recent decades. Projections consistently indicate a further doubling in the next ten years. It is recognised that genetic factors in addition to those controlling pigment variation can modulate the response of an individual to UVR. Several of the genetic factors affecting susceptibility to the development of squamous cell carcinoma, basal cell carcinoma and melanoma have been identified. Exposure to solar UVR down-regulates immune responses, in the skin and systemically, by a combination of mechanisms including the generation of particularly potent subsets of T regulatory cells. Such immunosuppression is known to be a crucial factor in the generation of skin cancers. Apart from a detrimental effect on infections caused by some members of the herpesvirus and papillomavirus families, the impact of UV-induced immunosuppression on other microbial diseases and vaccination efficacy is not clear. One important beneficial effect of solar UV-B is its contribution to the cutaneous synthesis of vitamin D, recognised to be a crucial hormone for bone health and for other aspects of general health. There is accumulating evidence that UVR exposure, either directly or via stimulation of vitamin D production, has protective effects on the development of some autoimmune diseases, including multiple sclerosis and type 1 diabetes. Adequate vitamin D may also be protective for the development of several internal cancers and infections. Difficulties associated with balancing the positive effects of vitamin D with the negative effects of too much exposure to solar UV-B are considered. Various strategies that can be adopted by the individual to protect against excessive exposure of the eye or the skin to sunlight are suggested. Finally, possible interactions between ozone depletion and climate warming are outlined briefly, as well as how these might influence human behaviour with regard to sun exposure. PMID- 17344961 TI - Terrestrial ecosystems, increased solar ultraviolet radiation, and interactions with other climate change factors. AB - There have been significant advances in our understanding of the effects of UV-B radiation on terrestrial ecosystems, especially in the description of mechanisms of plant response. A further area of highly interesting research emphasizes the importance of indirect UV radiation effects on plants, pathogens, herbivores, soil microbes and ecosystem processes below the surface. Although photosynthesis of higher plants and mosses is seldom affected by enhanced or reduced UV-B radiation in most field studies, effects on growth and morphology (form) of higher plants and mosses are often manifested. This can lead to small reductions in shoot production and changes in the competitive balance of different species. Fungi and bacteria are generally more sensitive to damage by UV-B radiation than are higher plants. However, the species differ in their UV-B radiation sensitivity to damage, some being affected while others may be very tolerant. This can lead to changes in species composition of microbial communities with subsequent influences on processes such as litter decomposition. Changes in plant chemical composition are commonly reported due to UV-B manipulations (either enhancement or attenuation of UV-B in sunlight) and may lead to substantial reductions in consumption of plant tissues by insects. Although sunlight does not penetrate significantly into soils, the biomass and morphology of plant root systems of plants can be modified to a much greater degree than plant shoots. Root mass can exhibit sizeable declines with more UV-B. Also, UV-B-induced changes in soil microbial communities and biomass, as well as altered populations of small invertebrates have been reported and these changes have important implications for mineral nutrient cycling in the soil. Many new developments in understanding the underlying mechanisms mediating plant response to UV-B radiation have emerged. This new information is helpful in understanding common responses of plants to UV-B radiation, such as diminished growth, acclimation responses of plants to UV-B radiation and interactions of plants with consumer organisms such as insects and plant pathogens. The response to UV-B radiation involves both the initial stimulus by solar radiation and transmission of signals within the plants. Resulting changes in gene expression induced by these signals may have elements in common with those elicited by other environmental factors, and generate overlapping functional (including acclimation) responses. Concurrent responses of terrestrial systems to the combination of enhanced UV-B radiation and other global change factors (increased temperature, CO2, available nitrogen and altered precipitation) are less well understood. Studies of individual plant responses to combinations of factors indicate that plant growth can be augmented by higher CO2 levels, yet many of the effects of UV-B radiation are usually not ameliorated by the elevated CO2. UV-B radiation often increases both plant frost tolerance and survival under extreme high temperature conditions. Conversely, extreme temperatures sometimes influence the UV-B radiation sensitivity of plants directly. Plants that endure water deficit stress effectively are also likely to be tolerant of high UV-B flux. Biologically available nitrogen is exceeding historical levels in many regions due to human activities. Studies show that plants well supplied with nitrogen are generally more sensitive to UV-B radiation. Technical issues concerning the use of biological spectral weighting functions (BSWFs) have been further elucidated. The BSWFs, which are multiplication factors assigned to different wavelengths giving an indication of their relative biological effectiveness, are critical to the proper conduct and interpretation of experiments in which organisms are exposed to UV radiation, both in the field and in controlled environment facilities. The characteristics of BSWFs vary considerably among different plant processes, such as growth, DNA damage, oxidative damage and induction of changes in secondary chemicals. Thus, use of a single BSWF for plant or ecosystem response is not appropriate. This brief review emphasizes progress since the previous report toward the understanding of solar ultraviolet radiation effects on terrestrial systems as it relates to ozone column reduction and the interaction of climate change factors. PMID- 17344962 TI - Effects of solar UV radiation on aquatic ecosystems and interactions with climate change. AB - Recent results continue to show the general consensus that ozone-related increases in UV-B radiation can negatively influence many aquatic species and aquatic ecosystems (e.g., lakes, rivers, marshes, oceans). Solar UV radiation penetrates to ecological significant depths in aquatic systems and can affect both marine and freshwater systems from major biomass producers (phytoplankton) to consumers (e.g., zooplankton, fish, etc.) higher in the food web. Many factors influence the depth of penetration of radiation into natural waters including dissolved organic compounds whose concentration and chemical composition are likely to be influenced by future climate and UV radiation variability. There is also considerable evidence that aquatic species utilize many mechanisms for photoprotection against excessive radiation. Often, these protective mechanisms pose conflicting selection pressures on species making UV radiation an additional stressor on the organism. It is at the ecosystem level where assessments of anthropogenic climate change and UV-related effects are interrelated and where much recent research has been directed. Several studies suggest that the influence of UV-B at the ecosystem level may be more pronounced on community and trophic level structure, and hence on subsequent biogeochemical cycles, than on biomass levels per se. PMID- 17344963 TI - Interactive effects of solar UV radiation and climate change on biogeochemical cycling. AB - This report assesses research on the interactions of UV radiation (280-400 nm) and global climate change with global biogeochemical cycles at the Earth's surface. The effects of UV-B (280-315 nm), which are dependent on the stratospheric ozone layer, on biogeochemical cycles are often linked to concurrent exposure to UV-A radiation (315-400 nm), which is influenced by global climate change. These interactions involving UV radiation (the combination of UV B and UV-A) are central to the prediction and evaluation of future Earth environmental conditions. There is increasing evidence that elevated UV-B radiation has significant effects on the terrestrial biosphere with implications for the cycling of carbon, nitrogen and other elements. The cycling of carbon and inorganic nutrients such as nitrogen can be affected by UV-B-mediated changes in communities of soil organisms, probably due to the effects of UV-B radiation on plant root exudation and/or the chemistry of dead plant material falling to the soil. In arid environments direct photodegradation can play a major role in the decay of plant litter, and UV-B radiation is responsible for a significant part of this photodegradation. UV-B radiation strongly influences aquatic carbon, nitrogen, sulfur and metals cycling that affect a wide range of life processes. UV-B radiation changes the biological availability of dissolved organic matter to microorganisms, and accelerates its transformation into dissolved inorganic carbon and nitrogen, including carbon dioxide and ammonium. The coloured part of dissolved organic matter (CDOM) controls the penetration of UV radiation into water bodies, but CDOM is also photodegraded by solar UV radiation. Changes in CDOM influence the penetration of UV radiation into water bodies with major consequences for aquatic biogeochemical processes. Changes in aquatic primary productivity and decomposition due to climate-related changes in circulation and nutrient supply occur concurrently with exposure to increased UV-B radiation, and have synergistic effects on the penetration of light into aquatic ecosystems. Future changes in climate will enhance stratification of lakes and the ocean, which will intensify photodegradation of CDOM by UV radiation. The resultant increase in the transparency of water bodies may increase UV-B effects on aquatic biogeochemistry in the surface layer. Changing solar UV radiation and climate also interact to influence exchanges of trace gases, such as halocarbons (e.g., methyl bromide) which influence ozone depletion, and sulfur gases (e.g., dimethylsulfide) that oxidize to produce sulfate aerosols that cool the marine atmosphere. UV radiation affects the biological availability of iron, copper and other trace metals in aquatic environments thus potentially affecting metal toxicity and the growth of phytoplankton and other microorganisms that are involved in carbon and nitrogen cycling. Future changes in ecosystem distribution due to alterations in the physical and chemical climate interact with ozone modulated changes in UV-B radiation. These interactions between the effects of climate change and UV-B radiation on biogeochemical cycles in terrestrial and aquatic systems may partially offset the beneficial effects of an ozone recovery. PMID- 17344964 TI - Changes in tropospheric composition and air quality due to stratospheric ozone depletion and climate change. AB - It is well-understood that reductions in air quality play a significant role in both environmental and human health. Interactions between ozone depletion and global climate change will significantly alter atmospheric chemistry which, in turn, will cause changes in concentrations of natural and human-made gases and aerosols. Models predict that tropospheric ozone near the surface will increase globally by up to 10 to 30 ppbv (33 to 100% increase) during the period 2000 to 2100. With the increase in the amount of the stratospheric ozone, increased transport from the stratosphere to the troposphere will result in different responses in polluted and unpolluted areas. In contrast, global changes in tropospheric hydroxyl radical (OH) are not predicted to be large, except where influenced by the presence of oxidizable organic matter, such as from large-scale forest fires. Recent measurements in a relatively clean location over 5 years showed that OH concentrations can be predicted by the intensity of solar ultraviolet radiation. If this relationship is confirmed by further observations, this approach could be used to simplify assessments of air quality. Analysis of surface-level ozone observations in Antarctica suggests that there has been a significant change in the chemistry of the boundary layer of the atmosphere in this region as a result of stratospheric ozone depletion. The oxidation potential of the Antarctic boundary layer is estimated to be greater now than before the development of the ozone hole. Recent modeling studies have suggested that iodine and iodine-containing substances from natural sources, such as the ocean, may increase stratospheric ozone depletion significantly in polar regions during spring. Given the uncertainty of the fate of iodine in the stratosphere, the results may also be relevant for stratospheric ozone depletion and measurements of the influence of these substances on ozone depletion should be considered in the future. In agreement with known usage and atmospheric loss processes, tropospheric concentrations of HFC-134a, the main human-made source of trifluoroacetic acid (TFA), is increasing rapidly. As HFC-134a is a potent greenhouse gas, this increasing concentration has implications for climate change. However, the risks to humans and the environment from substances, such as TFA, produced by atmospheric degradation of hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) are considered minimal. Perfluoropolyethers, commonly used as industrial heat transfer fluids and proposed as chlorohydrofluorocarbon (CHFC) substitutes, show great stability to chemical degradation in the atmosphere. These substances have been suggested as substitutes for CHFCs but, as they are very persistent in the atmosphere, they may be important contributors to global warming. It is not known whether these substances will contribute significantly to global warming and its interaction with ozone depletion but they should be considered for further evaluation. PMID- 17344965 TI - Effects of stratospheric ozone depletion and climate change on materials damage. AB - Nanoscale inorganic fillers with average particle sizes smaller by an order of magnitude or more compared to those of conventional fillers are becoming commercially available. The efficacy of these fillers used in polymer formulations and particularly their effect as photostabilizers are beginning to be investigated. These may enhance or retard photodegradation depending on the surface coating of the particles or their chemical nature. Some recent data indicate their use as effective photostabilizers in some common polymers. However, the potential deleterious interaction of the nanoscale fillers with other additives in the formulation has also been pointed out. Depending on the efficiency of stabilization and the economics of their use nanofillers may provide a useful route to UV-stabilization of plastics and rubber used outdoors. Insufficient data are available at this time to assess their potential impact on material and coatings stabilization. Organic fillers such as lignocellulose continue to be investigated for outdoor applications. Their cost advantage makes them attractive despite the somewhat reduced engineering properties of their composites. Recent reports, however, suggest the photostability of these composites to depend on the source of fiber as well as the processing techniques employed in fabricating products from them. Identification of the key determinants in terms of species, isolation and processing of polymer-wood composites is critical to developing them for long-term outdoor use. Efforts are continuing on the synthesis of new light stabilizers, particularly those based on a hindered amine light stabilizers (HALS), and on identifying synergistic combinations of known stabilizers for common thermoplastics. Variants of HALS type stabilizers that reduce the loss of stabilizer via leaching or migration were recently reported. Studies on the permanence of the stabilizers themselves when exposed to solar UV wavelengths have also been reported in recent work. Identification of relevant mechanisms is important not only to understand the interactions of climate changes and higher UV solar environments with materials damage, but also to guide future design of light-stabilizers. PMID- 17344966 TI - Questions and answers about the effects of the depletion of the ozone layer on humans and the environment. AB - The ozone molecule contains three atoms of oxygen and is mainly formed by the action of the ultraviolet rays of the sun on the diatomic oxygen molecules in the upper part of the Earth's atmosphere (called the stratosphere). Atmospheric pollution near the Earth's surface can form localized areas of ozone. The stratospheric ozone layer protects life on Earth by absorbing most of the harmful ultraviolet radiation from the sun. In the mid 1970s it was discovered that some manmade products destroy ozone molecules in the stratosphere. This destruction can result in damage to ecosystems and to materials such as plastics. It may cause an increase in human diseases such as skin cancers and cataracts. The discovery of the role of the synthetic ozone-depleting chemicals such as chlorofluorocarbons (CFCs) stimulated increased research and monitoring in this field. Computer models predicted a disaster if no action was taken to protect the ozone layer. Based on this research and monitoring, the nations of the world took action in 1985 with the Vienna Convention for the Protection of the Ozone Layer followed by the Montreal Protocol on Substances that Deplete the Ozone Layer in 1987. The Convention and Protocol were amended and adjusted several times as new knowledge was obtained. The Meetings of the Parties to the Montreal Protocol appointed three Assessment Panels to review the progress in scientific knowledge on their behalf. These panels are the Scientific Assessment Panel, the Technological and Economic Assessment Panel and the Environmental Effects Assessment Panel. Each panel covers a designated area and there is a natural level of overlap. The main reports of the Panels are published every four years as required by the Meeting of the Parties. All the reports have an executive summary that is distributed more widely than the main report itself. It became customary to add a set of questions and answers--mainly for non-expert readers- to the executive summaries. This document contains the questions and answers prepared by experts who comprise the Environmental Assessment Panel. It is based mainly on the 2006 report of the Panel but also contains information from previous assessments. Readers who need detailed information on any question should consult the full reports for a more complete scientific discussion. This set of questions refers mainly to the environmental effects of ozone depletion and climate change. The report of the Scientific Assessment Panel contains questions and answers related to the other scientific issues addressed by that Panel. All these reports can be found on the UNEP website (http://ozone.unep.org). PMID- 17344970 TI - [Transconjunctival vitrectomy: preliminary data using the TSV-25 Millennium System]. AB - PURPOSE: To report the preliminary surgical results of pars plana vitrectomy with a transconjunctival technique using the TSV-25 Millennium system. METHODS: Twenty consecutive patients (20 eyes) that underwent transconjunctival vitrectomy with the TSV-25 Millennium system, between July 2003 and January 2004, were prospectively postoperatively followed for a minimum period of one month. Eyes with macular hole, epiretinal membrane, macular edema, rhegmatogenous retinal detachment, endophthalmitis, and vitreous hemorrhage with or without tractional retinal detachment were included. Intra and post-operative complications and difficulties were recorded. RESULTS: All 20 patients completed at least one month postoperative follow-up. There were 4 macular holes, 2 epiretinal membranes, 2 cystoid macular edemas post-cataract surgery, 1 diabetic macular edema, 5 rhegmatogenous retinal detachments, 5 vitreous hemorrhages (2 associated with tractional retinal detachment), and 1 endophthalmitis. Mean postoperative day one intraocular pressure was 15.7 mmHg (6-46 mmHg) and at one postoperative month it was 14.2 mmHg (8-22 mmHg). There were no cases of sclerotomy-related retinal breaks, postoperative endophthalmitis, or ocular hypotony. Three of 5 eyes (60%) with retinal detachment needed further surgical intervention (all pseudophakic) and 4 of 5 eyes (80%) with vitreous hemorrhage had postoperative residual hemorrhage. All cases with macular diseases and phakic retinal detachments were successful with one surgery. CONCLUSION: This transconjunctival vitrectomy technique showed as its main benefits the low incidence of sclerotomy-related breaks and postoperative ocular hypertension. An adequate case selection seems to be crucial. PMID- 17344971 TI - [First Brazilian refractive surgery survey]. AB - PURPOSE: To perform the first Brazilian refractive surgery survey. METHODS: Between August 2001 and February 2002, a questionnaire was mailed to 7890 Brazilian ophthalmologists. The questionnaire presented questions about demographic aspects, technology, instruments, market, trends, practice patterns and cost of refractive surgery. RESULTS: Nine hundred and twenty questionnaires (11.67%) were answered. LASIK is the preferred technique for correction between +5.00 and -7.00 D. The mostly used excimer laser is Nidek EC 5000, and Hansatome is the mostly used microkeratome. Others aspects like: demographic, techniques, practice patterns, trends, market, and pre-, intra- and postoperative care, were analyzed. CONCLUSION: With this survey, the Brazilian ophthalmologists can observe and monitor these aspects of refractive surgery in Brazil, and compare them with others surveys. PMID- 17344972 TI - [Efficacy of pediatric cataract extraction with intraocular lens implantation]. AB - PURPOSE: To evaluate the efficacy of the use of intraocular lenses in the treatment of pediatric aphakia, according to postoperative visual acuity and refraction change. METHODS: A total of 33 eyes in 27 children were studied. Children with either unilateral or bilateral cataracts were submitted to lensectomy surgery via pars plana, with intraocular lens implant, associated with primary posterior capsulectomy and anterior vitrectomy. The intraocular lenses were calculated for emmetropia in the first postoperative month. All children were less than six years old at the time of the surgery and had a 2.9 year average follow-up. They were divided into 3 groups. Group I (10 eyes), children with unilateral cataracts and under three years old at the time of the surgery; group II (11 eyes), children with unilateral cataracts and above three years old; group III (12 eyes), children with bilateral cataracts and above three years old at the time of the surgery. RESULTS: On the last follow-up examination recorded visual acuity was equal to or above 20/40 in 85% of the eyes. A spherical equivalent close to emmetropia in the first postoperative month was obtained in 70% of the children of group III but only in 30% of group I. Regarding postoperative refraction variation, myopic shift was detected in 81.81% of the cases. The younger the children were when undergoing surgery, the greater the refractional alteration. CONCLUSION: Despite the myopic shift that happens with the use of intraocular lenses in the treatment of pediatric aphakia in children under six years old, the visual result is very good and the residual refraction correction is easily performed. A more prolonged postoperative follow-up would be necessary for long-term evaluation of the results. PMID- 17344973 TI - [A study of the applicability of biological adhesives to the insertion of an external ocular muscle in rabbits--II. Experiment II--Measurement of the distances from the nasal and temporal muscles to the limbus and of the extent of tissue adhesion]. AB - PURPOSE: Measure the extent of mioscleral adhesion on the fortieth postoperative day. METHODS: Fifteen New Zealand rabbits were divided into three groups of five rabbits. They were operated on to server the insertion of the rectus muscle in the eye and then to reinsert it. Group SP, polyglactin (Vicryl) was used as control. In group AF, fibrin adhesive (Beriplast-P) was used, and in group AC, cyanoacrylate adhesive (Histoacryl). Before severing muscle insertion, the distances between the muscle attachments of the limbus to the medial and lateral borders were measured. After forty-five days, the operation was again performed and the measurements were taken once more. RESULTS: There was no significant difference between the studied adhesives in terms of tissue adhesion and of the distances from the muscle to the limbus before and after surgery. CONCLUSION: The found tissue adhesion was probably due to the scarring process and was not dependent on the studied materials. PMID- 17344974 TI - [Focal electroretinography in normal young adults]. AB - PURPOSE: To determine normative values for focal electroretinography in normal young adults, according to the standard protocol recommended by the International Society for Clinical Electrophysiology of Vision-IsCEV. METHODS: 33 normal volunteers aged from 14 to 38 years (mean 22.96+/-5.73) were included in this study. Focal electroretinography was recorded by corneal electrode after white flicker light stimulation in the macula at high temporal frequencies -42Hz and 31.25Hz. Focal electroretinography parameters as amplitude (nanovolts) and latency (milliseconds) were extracted and analyzed after discrete Fourier transformation. Median, values below 95% and above 95%; maximum; minimum and percentiles were calculated for both parameters; a t test was calculated between amplitudes and latencies for both frequencies. RESULTS: For 42Hz. Amplitude: median 614nV; below 95% 529nV; above 95% 650nV; minimum 370 nV; maximum 794 nV; 2.5th percentile 378.8nV; 97.5th percentile 779.6nV. Latency: median 26.4ms; below 95% 25.4ms; above 95% 26.8ms; minimum 23.4ms; maximum 28.2ms; 2.5th percentile 23.8ms; 97.5th percentile 27.88ms. For 31.25Hz. Amplitude: median 632nV; below 95% 429nV; above 95% 750nV; minimum 364nV; maximum 1036nV; 2.5th percentile 364.8nV; 97.5th percentile 1018.4nV. Latency: median 30.1ms; below 95% 29.3ms; above 95% 31.2ms; minimum 25.9ms; maximum 33.9ms; 2.5th percentile 27.18ms; 97.5th percentile 33.34ms. CONCLUSIONS: Normal limits for focal electroretinography according to the International Society for Clinical Electrophysiology of Vision, guidelines were established in a cohort of young adults. Comparable amplitude values were found for both 42 Hz and 31.25 Hz temporal frequencies. However, latencies was significantly faster for 42 Hz stimuli. PMID- 17344975 TI - [Ocular manifestations in patients who had malnutrition in the first six months of life]. AB - PURPOSE: To investigate possible ophthalmologic alterations in patients who had severe malnutrition during the first six months of life. METHODS: 182 eyes of 91, 2 to 11-year-old, children who had had severe malnutrition during the first six months of life (study group) were analyzed. As a control group 88 children selected according to similar characteristics of age, gender, demographic and economic conditions were included. RESULTS: In the study group, a higher frequency of children with visual acuity from 0.3 to 0.1 and less than 0.1 (11.5% versus 0.7% - p< 0.0001) was observed. There was a higher frequency of astigmatism and myopia in the study group. A higher frequency of astigmatism of one diopter or more in the study group (p< 0.0001) was also observed. The fundoscopic alterations were pale optic nerve (2.2%), increased disc cup (4.4%), increased vascular tortuosity (6.6%), alteration of retina color (13.2%) and retinal pigment epithelium cell atrophy (12.0%). CONCLUSIONS: The present data support the concept that early malnutrition interferes in the individual's visual health. Further studies are necessary to establish a more precise cause-effect relationship. PMID- 17344976 TI - [Study of the impact of a MBA Administration in Health course on the organizational modernity of ophthalmologic clinics]. AB - PURPOSE: Investigations in the field of the learning competence that investigate the impact of the acquisition of new individual competence of those responsible for ophthalmologic clinics, by means of a MBA Administration in Health course, on the organizational modernity of ophthalmologic clinics. METHODS: Survey using questionnaires applied to students and former students of the course and to managers of ophthalmologic clinics not linked to the course (n=30 each one). The analysis was made by means of statistical methods: r of Pearson and Q of Yule; Student's t test, sum of series test, median test and U test of Mann-Whitney. RESULTS: Linear and positive correlation was observed between excellency of MBA Administration in Health and the development of the veteran students' capacities (rho correlation of Spearman at the level of 0.01); there is a significant difference (0.0364, by the Mann-Whitney test), between veteran students and freshmen regarding the need to extend the individual capacities provided by the MBA Administration in Health course, to the other operational employees of the ophthalmologic clinics; and there is a significant difference (0.0057, for the Mann-Whitney test), among veteran students of the MBA Administration in Health course and freshmen regarding the importance of the organizational modernity for the ophthalmologic clinics. CONCLUSIONS: The obtained results are consistent, in a general way, with the proposed model: MBA Administration's excellence in Health contributes significantly to the organizational modernity, to the development of competence of the veteran students, and, also in substantial way to the perception of organizational hiatuses. PMID- 17344977 TI - [Study of torsional movements in refractive surgery]. AB - PURPOSE: To observe torsional movements of the eye in refractive surgery, and their possible consequences in the surgery outcome. METHODS: In a prospective study, 49 eyes of 40 patients were submitted to surgical correction of astigmatism, by the LASIK technique. Patients were divided in two groups based on the cylindric power. Group A from -0.25 to -2.00D; group B from -2.25 to -6.00D. The occurrence of torsional movements was recorded in all patients, and based on this, the axis of treatment was corrected. RESULTS: Mean torsion was 3.5 masculine +/- in group A; and 4.5 masculine+/- in group B. There was no statistical difference between the two groups. CONCLUSION: Torsional movements occurred in almost all cases, and therefore should be corrected if one desires best results. This is specially important in matching personalized data captured in wave front analyzers for the eye at the time of surgery. PMID- 17344978 TI - [Ocular involvement in AIDS patients with central nervous system toxoplasmosis: before and after HAART]. AB - PURPOSE: To describe the ophthalmologic involvement in patients with Acquired Immunodeficiency Syndrome-AIDS and central nervous system toxoplasmosis comparing the period before and after highly active antiretroviral therapy (HAART). METHODS: In a retrospective study, we compared 118 Acquired Immunodeficiency Syndrome patients with central nervous system toxoplasmosis who were examined at our institution before highly active antiretroviral therapy (from 1994-1996) with 24 patients with Acquired Immunodeficiency Syndrome and central nervous system toxoplasmosis who were being treated with highly active antiretroviral therapy (from 1996-1999). All patients were submitted to a complete ophthalmological examination as well as specific tests to confirm the diagnosis and there was no intersection between the groups. RESULTS: In the pre-highly active antiretroviral therapy group, it was found that 23% of the patients with central nervous system toxoplasmosis had also ocular toxoplasmosis. Ocular involvement was bilateral in 37.2% of the cases. In the group of patients receiving highly active antiretroviral therapy, who had an average CD4 of 256 cells/mm(3) and average of viral load of 52,620 copies, 16.6% had concomitant ocular and central nervous system toxoplasmosis. Ocular involvement was bilateral in 50% of the cases. CONCLUSIONS: Acquired Immunodeficiency Syndrome patients with central nervous system toxoplasmosis have a frequent association with ocular toxoplasmosis. Although the incidence of opportunistic infections has decreased since the introduction of recent antiretroviral therapeutic strategies ocular toxoplasmosis continues to be frequent in patients with cen.ral nervous system toxoplasmosis. PMID- 17344979 TI - [Development and validation of the MNREAD reading acuity chart in Portuguese]. AB - PURPOSE: To create and to validate a version of the Minnesota Low Vision Reading Test (MNREAD) acuity chart for the Portuguese language. METHODS: The Minnesota Low Vision Reading Test acuity chart contain 19 sentences (logMAR 0.5 to 1.3) with 60 characters printed on three lines. All the sentences must have the same length with simple vocabulary. A total of 110 sentences were generated. The sentences were presented to 36 subjects (20 adults and 16 children) and mistakes and reading time were marked. 38 sentences were selected for a prototype (MNREAD P). Sentences with extreme high and low mean reading time, large standard deviation, and with persistent mistakes by subjects were excluded. VALIDATION: Twenty subjects with normal vision (logMAR 0 or 20/20 or better, with best refractive correction) were tested with the MNREAD-P and read a passage of text, representing normal, day-to-day reading. Reading speeds in words per minute were recorded for both the MNREAD and the text passage. RESULTS: Sentences in the MNREAD Portuguese chart are sufficiently consistent to provide reliable measures of reading abilities. Reading speeds for the passage (logMar = 0.6) were 197.8 words/minute and the maximum reading speeds calculated by the MNREAD-P were 200.1 words/minute. The correlation between the two measures was r = 0.82. CONCLUSION: The MNREAD-P was tested on normal vision subjects and the results were the same from the original Minnesota Low Vision Reading Test. The reading speed measured on the MNREAD-P was statistically equivalent to the reading speed of the passage. PMID- 17344980 TI - [A comparative study of the manual and digital measurements of the palpebral fissure]. AB - PURPOSE: To compare the measurement of the palpebral fissure done either manually and by computer analysis of image of individuals without lid alterations. METHODS: One hundred two palpebral fissures from 51 normal subjects have been analyzed. The patients' age ranged from 17 to 84 years, with 25 (49%) males and 26 (51%) females. RESULTS: There was no statistically significant difference between the measurements done either manually or by computer analysis of images, neither, when we grouped the patients by sex or age. Also we did not observe difference between males and females, and regarding age. CONCLUSIONS: The results obtained by both methods are comparable and reliable due to the statistical equivalence of the obtained measurements. PMID- 17344981 TI - [Evaluation of the impact of refractive surgery on quality of life using the NEI RQL (National Eye Institute Refractive Error Quality of Life) instrument]. AB - PURPOSE: To assess the impact of refractive surgery on quality of life using the National Eye Institute Refractive Error Quality of Life instrument (NEI-RQL) and to evaluate the responsiveness of our Portuguese version of the NEI-RQL instrument to surgical correction of refractive error. METHODS: In this prospective study, the NEI-RQL, a 42-item questionnaire with 13 scales, was self administered by 96 patients of the Federal University of Sao Paulo-UNIFESP, between March 2002 and April 2003, before and after undergoing surgical correction of refractive error. An overall scale score was determined by calculating the mean of the 13 scale scores. Differences between preoperative and postoperative NEI-RQL scores were examined. Responsiveness was assessed by calculating the size of effect for each scale of the instrument. RESULTS: Refractive surgery was associated with statistically significant improvements in scores for all the scales of the NEI-RQL. The NEI-RQL has shown to be responsive to surgical correction of refractive error, and the calculated effect sizes ranged from 0.4 ("glare") to 4.19 ("expectations"). CONCLUSIONS: The NEI-RQL is highly responsive to changes in vision-related quality of life resulting from keratorefractive surgery. We observed improvements in all the scales of the NEI RQL, after surgery. PMID- 17344982 TI - [Different techniques for Placido image analysis may improve precision of videokeratography]. AB - PURPOSE: Videokeratography (VK) has been a widespread technology for corneal surface analysis since the mid-80s. The objective of this study was to develop different techniques for Placido image edge detection and compare the results of each algorithm in terms of the consequences for axial curvature computations. METHODS: Placido images from an Eyesys system 2000 were captured for 4 different spherical surfaces. Each image was saved in bitmap format at the hard disk of an IBM computer. Six different image-processing algorithms were developed using different techniques well-documented in the literature. The six methods were as follows: (1) First order numerical derivative, (2) First and (3) Second order Fourier derivative, (4) the Marr-Hildreth filter, (5) Canny's Method, (6) Mathematical morphology. Each algorithm was tested on each of the Placido images. RESULTS: Edge radial distance from center of Placido image was compared for each algorithm and a computer simulation of the videokeratography system. Mean deviation in terms of pixels/millimeters/dioptric power for all spheres for methods (1)-(6) were, respectively: (1) 33.1695/0.7961/0.79, (2) 32.79/0.7870/0.7724, (3) 60.7150/1.4572/1.4192, (4)18.97/0.4553/0.4572, (5) 46.33/1.1119/1.0917, (6) 20.55/0.4932/0.48. CONCLUSION: Researchers and clinical ophthalmologists should be more careful when choosing commercial videokeratographs and also when comparing measurements of different instruments, given that there may be differences associated with the image processing technique. We have shown here that the Marr/Hildreth (method (4)) image processing method is more precise than other methods such as Fourier or first order numerical methods. PMID- 17344983 TI - [Organizational ethics: a study in ophthalmologic clinics]. AB - PURPOSE: Research on the field of organizational ethics to investigate to which extent ophthalmologic clinics, inserted in the competitive atmosphere, in the condition of organizations in search of survival, subordinate ethics to competitiveness in the managerial praxis, that is, in the administrative sphere. METHODS: Kohlberg is taken as theoretical reference, approaching the theme of ethical subordination to competitiveness. The instrument to evaluate moral behaviors of organizations, elaborated by Licht, is applied. The quantitative method is used, adopting analytic instruments, such as Q of Yule and non parametric tests, when dealing with the data of 41 ophthalmologic clinics. RESULTS: The results of the research seem to indicate that administrators of ophthalmologic clinics of greater performance subordinate ethical principles to competitiveness, seeking to assure the survival of the company and, when confronted with the instrument to evaluate their moral behavior, proposed by Kohlberg, have a significantly smaller presence in the postconventional stage than administrators of ophthalmologic clinics with a smaller performance. One may affirm, according to non parametric tests, at the level of significance of 0.05, that the levels of moral development of the two groups differ significantly. CONCLUSIONS: The obtained results are according to the literature, especially concerning the "paradox of the ethical subordination and competitiveness". They also suggest that the warrant of the survival of the company tends to reduce the perception of the groups in power regarding the problems that happen in the community, and that a reduction of the ethical values subordinated to competition occurs, and such reduction provokes growing feelings of economical disputes in the social sphere. PMID- 17344984 TI - [Critical analysis of the progressive performance of low vision in Benjamin Constant Institute]. AB - PURPOSE: To evaluate effectiveness of the Low Vision the Benjamin Constant Institute (BCI) and confirm the real necessity of an Institute like BCI in the present inclusion policy. METHODS: Ecological study, analyzing 3 periods of Low Vision Assistance at the Benjamin Constant Institute from October 1, 1990 to December 20, 2002: a) 1991--starting assistance; b) 1995--medical pedagogic integration; c) 2002--present-day situation. We considered in this analysis as indicators: I--Low Vision Assistance, II--Low Vision sector in the Benjamin Constant Institute, III--Associates. RESULTS: This study demonstrated an increase in assistance, reaching a wider spectrum of patients after medical-pedagogic integration. Other indicators, such as physician capacitation, participation in Benjamin Constant Capacitation Courses, increase in orientation to institutions, schools and others and referrals to the Benjamin Constant Institute, and Rehabilitation also attest the effectiveness of the Low Vision sector of the Benjamin Constant Institute. CONCLUSIONS: The Low Vision sector proved to be the interface between the Medical and Pedagogic Departments, and later on the Rehabilitation and Physical Education Coordination sectors. This has implied alterations in the way to manage the low-vision patient, not only regarding the regular Benjamin Constant Institute student as well as any other patient in the community. The Benjamin Constant Institute proved its importance as regards inclusion policy. PMID- 17344985 TI - Superficial corneal foreign body: laboratory and epidemiologic aspects. AB - PURPOSE: To determine by bacterioscopy and culture the microorganisms carried by corneal foreign body and their sensitivity to antibiotics by antibiotic sensitivity test. METHODS: A prospective study was carried out and information was collected on 101 patients who presented with corneal foreign body at the Sao Paulo Hospital Eye Emergency Service. Prior to any treatment, a sample of the ipsilateral inferior conjunctival fornix and the foreign body were collected and immersed in thioglycolate broth. Samples were sown on solid culture media including blood, chocolate and Sabouraud agar. Bacterioscopic examination using Gram and Giemsa staining and sensitivity test were performed. Positive foreign body culture results were compared to ipsilateral conjunctival fornix culture to exclude possible normal flora growth. RESULTS: Approximately 92% of patients were males with a mean age of 35 years and in 62.4% (95% confidence interval: 52.2 71.8%) had the right eye was affected. Foreign body positive cultures were achieved in 32.7% (95% confidence interval: 23.7-42.7%) of the cases. The microorganisms isolated from the foreign body culture were identified as: Streptococcus, alpha-hemolytic (n=4), Staphylococcus aureus (n=4), Staphylococcus, coagulase-negative (n=4), Corynebacterium xerosis (n=3), unidentified Gram-positive bacillus (n=2), Moraxella sp (n=1), Serratia sp (n=1), Acynetobacter sp (n=1). The microbial sensitivity test showed that 95% of the cases were sensitive to chloramphenicol and 90% were sensitive to ciprofloxacin, these being antibiotics used in our routine service. CONCLUSION: Superficial corneal foreign body acts as important contaminant vector and the great majority of isolated bacteria were sensitive to the antibiotic prophylaxis used in the treatment. PMID- 17344986 TI - [Conjunctival microbiota in patients with ocular allergy]. AB - PURPOSE: To evaluate de presence of conjunctival aerobic microbiota in patients with ocular allergy as compared to a control group. METHODS: One hundred and thirty-three patients were evaluated from April to June 2001 and divided into 2 groups. Sixty-three patients with allergic conjunctivitis (without medication) were in group A and 70 patients from the general outpatient clinic were in group B (control group). Samples from the conjunctival sac of the right eye were collected and cultured in solid media (blood, chocolate and Sabouraud agar). RESULTS: In group A, 30 cultures (47.7%) were positive and 6 (8.6%) in group B. Seven bacteria were isolated from group A and 4 from group B. Statistical analysis revealed significant association between positive cultures and allergic conjunctivitis. CONCLUSION: Bacterial microbiota was more frequently found in patients with ocular allergy. PMID- 17344987 TI - [Infectious keratitis in children: an epidemiological and microbiological study in a university hospital in Asuncion-Paraguay]. AB - PURPOSE: To describe the microbiologic aspects of infectious keratitis in children (0-18 years old) examined at the Department of Ophthalmology of the National University of Asuncion-Paraguay, during a 14-year period (1988-2002). METHODS: The authors retrospectively studied 146 children, under 18 years old, with infectious keratitis at the Department of Ophthalmology of the National University of Asuncion-Paraguay, from 1988 to 2002. RESULTS: The cultures were positive in 113 patients (77%) with 70% of bacterial and 30% of fungal etiology. Coagulase-negative Staphylococcus (23.1%), Staphylococcus aureus (19.2%), Pseudomonas aeruginosa (12.8%) and Streptococcus pneumoniae (12.8%) were the most common microorganisms isolated. Acremonium ssp (25%), Fusarium ssp (14%) and Aspergillus fumigatus (14%) were the fungi isolated. CONCLUSIONS: Ulcerative keratitis in children examined at the Department of Ophthalmology of the National University of Asuncion-Paraguay is of bacterial origin in most of the cases. PMID- 17344988 TI - [Atypical presentation of pellucid marginal degeneration: case report]. AB - The authors report an unusual clinical presentation of pellucid marginal degeneration with 360 masculine peripheral corneal thinning diagnosed in a younger male patient. We discuss the findings of topographic maps, ultrasound pachymetry and the proposed treatment. PMID- 17344989 TI - [Macular infarction after intravitreal injection of amikacin: case report]. AB - The authors report a case of a patient who underwent cataract surgery with implantation of a posterior chamber intraocular lens and presented endophthalmitis on the second postoperative day. She was treated with intravitreal injection of amikacin, vancomycin and dexamethasone. After resolution of the infection the patient presented macular infarction and important loss of visual acuity due to amikacin toxicity. PMID- 17344990 TI - [Ectopia lentis et pupillae: case report]. AB - The main purpose of this report is to describe a case of ectopia lentis et pupillae syndrome, highlighting the secondary ocular complications and their differential diagnoses. A 27-year-old man presented with complaint of low visual acuity. No evidence of the syndrome was found at presentation. The results of supplementary tests were normal. On ophthalmologic examination, visual acuity was finger count at 2 meters in the right eye and finger count at 1 meter in the left eye. Exotropia of 25 dioptrics. Corneal diameters of 10 mm and 9 mm in the horizontal and vertical meridians, respectively. Keratometry readings of 39.00 at 178 x 43.87 at 88 for the right eye and 37.64 at 22 x 42.75 at 122 for the left eye. The biomicroscopic examination revealed iris atrophy in both eyes, absence of crypt and absent iris transillumination. Centralized right pupil with regular form and left pupil with inferior-temporal dislocation. Opaque lenses with reduced sizes and superior-nasal dislocation. Normal intraocular pressure. Axial length of 26 mm and 30 mm and crystalline axial diameter of 5.4 and 4.5 mm in right and left eyes, respectively, as revealed by ultrasonography. The differential diagnosis encompasses exclusively ocular abnormalities, syndromes and metabolic disorders. Diagnosis of the ectopia lentis et pupillae is fundamental not only to evaluate the risk, prognosis and treatment, but also to assist in differentiating other syndromes with systemic impairment. A visual acuity reduction is normally caused by severe myopia development, cataract, corneal astigmatism, retinal detachment and glaucoma, justifying regular ophthalmologic support for these patients. PMID- 17344991 TI - [Idiopathic vasoproliferative tumor of the retina associated with macular edema: case report]. AB - Retinal vasoproliferative tumor is a rare and benign disease that presents with an exsudative lesion in the retinal periphery. The lesion can be classified as primary (idiopathic) or secondary to a number of previous retinal injuries. Diagnosis is based on a careful ophthalmic examination. Therapeutic options include observation, cryotherapy, laser photocoagulation and brachytherapy. We present a case of idiopathic retinal vasoproliferative tumor associated with macular edema. The aspects of the tumor on fundus examination, fluorescent angiography, echography and optic coherence tomography are discussed. PMID- 17344992 TI - [Cogan's Syndrome: case report]. AB - Non-luetic interstitial keratitis, deafness and vertigo characterize Cogan's syndrome. The most common ocular findings in early Cogan's syndrome are bilateral, peripheral, subepithelial numular corneal opacities. The report presents a patient with the evolution of the classic form of Cogan's syndrome. PMID- 17344993 TI - [Ocular alterations associated with bungee jumping: case report]. AB - The popularization of bungee jumping is causing an increase in occurrences of lesions associated with its practice, including ocular lesions. The purpose of this study is to describe a case of acute decrease in vision and visual field defects following a bungee jump. The authors present a case of a 48-year-old woman, without history of systemic or ocular disorders, seen at an ophthalmologic emergency service with visual loss complaint following a bungee jump. On initial ophthalmologic evaluation, hemorrhages in the posterior pole of both eyes were found. Fluorescein angiography showed hypofluorescent areas, without other vascular alterations. The patient was evaluated after 14 weeks, the hemorrhages cleared up and there was atrophy of the pigmented epithelium of the retina in the posterior pole, but the patient remained with complaint of scotoma and visual field defects even 5 months after the initial event. The occurrence of body lesions, including ocular lesions, with risk of decrease in visual acuity should be informed to candidates for the practice of this sport, and the ophthalmologist would do well to provide information to the population about possible ocular disorders, in this sport and in daily life. PMID- 17344994 TI - [Congenital corneal anesthesia related to trigeminal anesthesia: case report]. AB - Corneal anesthesia is a rare condition, therefore its diagnosis is frequently impaired or it is not noticed during the anterior segment examination. Case report of a 18-year-old patient referred to our Corneal and External Disease Department who complained of dry eye symptoms and with a suspicion of Sjogren's syndrome. She had amblyopia of the right eye, consequence of corneal leucoma over the visual axis secondary to a fingernail traumatism inflicted by herself in childhood. On the ophthalmologic examination corneal sensitivity was absent in both eyes. Severe dry eye and breakup time less than four seconds. Diagnosis of congenital corneal anesthesia was established, secondary to trigeminal anesthesia found on neurological evaluation of facial sensitivity. She also showed sudden movements of the chin which evidenced sensorial pathology of the trigeminal nerve. The general ophthalmologist and specially anterior segment specialists must perform tests for corneal sensitivity during the routine eye examination. PMID- 17344995 TI - [Geniculate hemianopia. Diagnostic importance of retinal nerve fiber layer analysis using optical coherence tomography: case report]. AB - Lesions of the lateral geniculate body (LGB) are the most unusual lesions of the visual pathways. Imaging studies are very important in establishing the correct diagnosis. However, due to its small size and particular location, the lateral geniculate body and its lesions are sometimes difficult to detect in imaging studies possibly causing diagnostic confusion. The purpose of this paper is to document an unusual case of a lesion of the lateral geniculate body for which an optical coherence tomography study was very important in confirming the anatomic diagnosis of a lateral geniculate body lesion. A 39-year-old woman with a previous diagnosis of uveitis and central nervous system vasculitis was referred for investigation of a right temporal quadrantanopia. She had already been submitted to a magnetic resonance imaging (MRI) that did not show any lesion along the visual pathway. Ophthalmoscopy revealed retinal nerve fiber layer (RNFL) loss that was confirmed by optical coherence tomography. Such finding associated with the observations on the neurological examination strongly suggested a lateral geniculate body lesion. The patient was submitted to another new magnetic resonance imaging obtained with especially oriented thin sections and an ischemic lesion of the lateral geniculate body was observed establishing the correct diagnosis. This case serves to confirm the importance of optical coherence tomography in determining the pattern of retinal nerve fiber layer loss in neuro-ophthalmic diseases and therefore to help in locating a lesion along the visual pathway. PMID- 17344996 TI - Spontaneous late in-the-bag intraocular lens dislocation after can-opener capsulotomy: case report. AB - We report a case of a 58-year-old man presenting with a spontaneous and late in the-bag intraocular lens dislocation to the vitreous. A previous uneventful extracapsular cataract extraction with can-opener style capsulotomy and implantation of a polymethylmethacrylate three-piece lens was performed and, two years after the surgery, the patient developed capsule contraction syndrome with a fibrotic ring formation and dislocation of the intraocular lens. Although uncommon and related mainly to continuous curvilinear capsulorhexis, capsule contraction syndrome occurs in patients undergoing extracapsular cataract surgery with can-opener style and polymethylmethacrylate lens implantation, and can be the causative factor of intraocular lens dislocation. PMID- 17344997 TI - [Mitomycin C and excimer laser]. AB - Mitomycin C is an antimetabolite agent that blocks DNA and RNA replication and protein synthesis. It has been used in several ophthalmologic areas, and recently as a modulator of corneal wound healing in excimer laser surgeries. A single application of mitomycin C during surface corneal photoablative surgery seems a safe and efficient therapeutic option for eyes with corneal opacity and/or as prophylaxis in eyes with high risk for corneal opacity development. The use of this drug in photoablative surgery should be cautious until long-term safety results have been reported. The present text presents a review about corneal wound healing with the use of mitomycin C. PMID- 17344998 TI - Cadavers as teachers in medical education: knowledge is the ultimate gift of body donors. AB - In most of the medical colleges in India, unclaimed bodies from various mortuaries reach the dissection hall; and here, the body donors club has yet to gain the desired dimensions. In spite of all the adverse circumstances, the cadaver and the dissection both have survived the most rigorous test of pedagological fitness--the test of time. Today, many of the Western countries have long donor waiting lists where cadavers are acquired as anatomical gifts or through body donor programmes. Thailand's approach to body donors offers a role model for resolving the present situation. The spirit of volunteerism reflects the drastic shift in public perception and a global change in approach is needed in the present time. PMID- 17344999 TI - [Innovative wound therapy and skin substitutes for burns]. AB - The success of modern burn therapy is based mainly on special burn intensive care, topical treatment, early eschar excision, and wound closure by immediate skin grafting or skin substitutes. This paper describes the current state of wound care and skin substitutes in burn therapy. PMID- 17345000 TI - [Crossover extremity transfers. Limb salvage in amputations with segmental defects]. AB - Clinical conditions in which crossover extremity transfer should be considered are rare. In the case of bilateral amputation associated with extensive proximal segmental injury, ectopic implantation could be an additional concept for two stage limb salvage. If replantation is impossible due to segmental damage of the amputated part, at least uninvolved tissue should be harvested for stump lengthening or improving soft-tissue at the ends. The case of a 34-year-old man with segmental amputation of the left forearm and left lower leg and mutilated amputation of the right hand caused by a train accident is presented. Limb salvage was performed by cross-hand replantation and modified rotationplasty of the left foot as a stump lengthening procedure. PMID- 17345001 TI - Eosinophilic fasciitis: report of two cases and a systematic review of the literature dealing with clinical variables that predict outcome. AB - We reported two patients with refractory eosinophilic fasciitis (EF) and provided a systematic review of the literature to determine the clinical variables associated with prognosis of EF. We enrolled 88 cases, whose clinical characteristics were analyzed by separating the patients into two or three groups based on outcome. The incidence of certain clinical and pathological features differed among the groups. In particular, the incidence of morphea-like skin lesions in patients with refractory fibrosis was significantly higher than in patients without refractory fibrosis (p = 0.003). Patients with morphea-like skin lesions were 1.9 times more likely to develop persistent fibrosis than patients without these lesions (95% confidence intervals, 1.5-2.5). A younger age (under 12 years) at onset was associated with a 1.6 times greater risk of residual fibrosis (95% confidence interval, 1.1-2.2). Trunk involvement was associated with a 1.4 times greater risk of residual fibrosis (95% confidence interval, 1.0 2.0). Histopathologically, the presence of dermal fibrosclerosis was associated with a 1.4 times greater risk of refractory fibrosis (95% confidence interval, 1.0-2.1). We consider these clinical characteristics, notably the presence of morphea-like skin lesions may be an important risk factor for developing residual fibrosis in EF patients. PMID- 17345002 TI - Peri-operative morbidity and early results of a randomised trial comparing TVT and TVT-O. AB - The aim of this study was to compare the morbidity and short-term efficacy of retro-pubic (TVT) and inside-out trans-obturator (TVT-O) sub-urethral sling in the treatment of stress urinary incontinence. This was a prospective multi-centre randomised trial; 231 women with primary stress urinary incontinence were randomised to TVT (114) or TVT-O (117). The International Consultation on Incontinence-Short Form (ICIQ-SF), Women Irritative Prostate Symptoms Score (W IPSS) and Patient Global Impression of Severity (PGI-S) questionnaires were used to evaluate the impact of incontinence and voiding dysfunction on QoL and to measure the patient's perception of incontinence severity. The primary and secondary outcome measures were rates of success and complications. The SPSS software was used for data analysis. The TVT-O procedure was associated with significantly shorter operation time and with a more extensive use of general anaesthesia when compared with TVT. There were 5 (4%) bladder perforations in the TVT group compared with none in the TVT-O group. Rates of early post-operative urinary retention and voiding difficulty were similar for both groups and no difference was found in the average hospital stay. Six patients (5%) in the TVT-O group complained of thigh pain in the post-operative course. The median follow-up time was 6 months. Two hundred eighteen patients were available for the analysis of outcomes. Subjective and objective cure rates were 92% and 92% in the TVT group and 87% and 89% in the TVT-O group. The ICIQ-SF questionnaire symptoms score showed a highly statistical decrease in both groups, the W-IPSS on the contrary was unchanged. Our data show that both procedures were equally effective in the short-term for the treatment of stress urinary incontinence with a highly significant improvement in incontinence-related QoL. PMID- 17345003 TI - A computer-aided multidisease diagnostic system using MRCP. AB - Automated computer analysis of magnetic resonance cholangiopancreatography (MRCP) (a focused magnetic resonance imaging sequence for the pancreatobiliary region of the abdomen) images for biliary diseases is a difficult problem because of the large inter- and intrapatient variations in the images, varying acquisition settings, and characteristics of the images, defeating most attempts to produce computer-aided diagnosis systems. This paper proposes a system capable of automated preliminary diagnosis of several diseases affecting the bile ducts in the liver, namely, dilation, stones, tumor, and cyst. The system first identifies the biliary ductal structure present in the MRCP images, and then proceeds to determine the presence or absence of the diseases. Tested on a database of 593 clinical images, the system, which uses visual-based features, has shown to be successful in delivering good performance of 70-90% even in the presence of multiple diseases, and may be useful in aiding medical practitioners in routine MRCP examinations. PMID- 17345004 TI - Phase II study of CT-2103 as first- or second-line chemotherapy in patients with metastatic breast cancer: unexpected incidence of hypersensitivity reactions. AB - This study evaluated the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamate, in patients with HER2-negative, metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy. Although CT 2103 had activity in this small study, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected, and led to early termination of the trial. PURPOSE: To evaluate the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamate, in patients with metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy. PATIENTS AND METHODS: Eighteen women with HER2-negative breast cancer were enrolled. Patients received intravenous CT-2103 at a dose of 175 mg/m2 of conjugated paclitaxel over 10 min every 3 weeks, without routine premedication. Eighty-three percent of women had received prior chemotherapy as part of adjuvant (39%), metastatic (17%), or both adjuvant and metastatic (28%) treatment. Three patients (17%) had previously received a taxane in the adjuvant setting. RESULTS: Objective responses were observed in 4 of 18 patients (overall response rate, 22%, 95% confidence interval, 6 to 48%). Grade 3 or 4 neuropathy was observed in four patients. Grade 3 or 4 hypersensitivity reactions (HSR) were observed in four patients; none occurred prior to cycle 4 of therapy. Because of the higher than-expected rate of HSR, the study was terminated early. CONCLUSION: Although CT-2103 had activity in this small study of women with HER2-negative metastatic breast cancer, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected. Hypersensitivity reactions were most likely to occur in later cycles of treatment, suggesting a true drug allergy, distinct from the HSR typically seen with standard paclitaxel. PMID- 17345005 TI - Spatial patterns of tungsten and cobalt in surface dust of Fallon, Nevada. AB - Spatial patterns of tungsten and cobalt are described for surface dust of Fallon, Nevada, where a cluster of childhood leukemia has been ongoing since 1997. In earlier research, airborne tungsten and cobalt was shown to be elevated in total suspended particulates in Fallon. To fine-tune the spatial patterns of tungsten and cobalt deposition in Fallon, surface dust was collected in a grid pattern within as well as outside of Fallon to establish background concentrations of metals. In surface dust, tungsten and cobalt show sharp peaks (934 ppm and 98 ppm, respectively) within Fallon just north of highway 50 and west of highway 95. These two peaks overlap spatially, and given the grid pattern used for collecting surface dust, the source area of these two airborne metals can be pinpointed to the vicinity of hard-metal industry located north of highway 50 and west of highway 95. Fallon is distinctive in west central Nevada because of high airborne tungsten and cobalt particulates, and given its cluster of childhood leukemia, it stands to reason that additional biomedical research is in order to test directly the leukogenicity of combined airborne tungsten and cobalt particulates. PMID- 17345006 TI - Water quality assessment at Omerli Dam using remote sensing techniques. AB - Water quality at Omerli Dam, which is a vital potable water resource of Istanbul City, Turkey was assessed using the first four bands of Landsat 7-ETM satellite data, acquired in May 2001 and water quality parameters, such as chlorophyll-a, suspended solid matter, secchi disk and total phosphate measured at several measurement stations at Omerli Dam during satellite image acquisition time and archived at the Marine Pollution and Ecotoxicology laboratory of the Marmara Research Center, where this study was carried out. Establishing a relationship between this data, and the pixel reflectance values in the satellite image, chlorophyll-a, suspended solid matter, secchi disk and total phosphate maps were produced for the Omerli Dam. PMID- 17345007 TI - Assessment of farmland sediments after flooding in Ubeji Land in Niger Delta of Nigeria. AB - A study was conducted to evaluate ten heavy metals in dry sediment samples used to assess the contamination of farmland in Niger Delta after a protracted flooding. Eighteen sediment samples in six locations were collected. Niger Delta is a major industrial area where Nigeria petrochemical company is located. These sediments were subjected to analysis using standard methods for the examination of the soil samples. Results showed a trend toward induction of environmental contamination with Zn, Cu, Fe, Hg and Pb on the farmland. Mercury and Lead are disproportionately higher than other sediment elements. Concentrations of these sediment elements are above compliance limit for Nigeria and these may have long term adverse effects on soil and vegetation. PMID- 17345008 TI - The effects of landscape-level disturbance on the composition of Minnesota caddisfly (Insecta: Trichoptera) trophic functional groups: evidence for ecosystem homogenization. AB - Over 300,000 caddisfly specimens representing 249 species were collected from nearly 250 sites throughout Minnesota during 2000 and 2001 to determine the effects of human disturbance on the composition of caddisfly trophic functional groups at the landscape level. Canonical correspondence analysis determined that stream width was the most important variable influencing functional group composition in regions of the state with relatively low disturbance, and that differences in the caddisfly fauna between sizes of streams generally followed trends predicted by the river continuum concept. In regions of the state with moderate disturbance, both stream width and the percentage of disturbed habitat upstream of a site were important variables influencing functional group composition. In highly disturbed regions, no variables corresponded to changes in the composition of caddisfly functional groups. Instead, ecosystems were homogeneous: fine-particle filtering collectors dominated in all sizes of streams. The observed aquatic ecosystem homogenization is attributed mostly to input of fine-particle organic and inorganic sediment from extensive agriculture. PMID- 17345009 TI - Eutrophication conditions and ecological status in typical bays of Lake Taihu in China. AB - Sampling was conducted at three site groups, group E (in East Taihu Bay), G (in Gonghu Bay) and M (in Meiliang Bay) in Lake Taihu. TN and TP concentrations among site groups was in the increasing order of E < G < M. TP level at G sites is at the critical threshold for loss of submersed macrophytes. Mean values of DO and Transparence showed different trend, i.e., E > G > M. The mean phytoplankton fresh-weight biomass at M sites was 5.81 mg/l, higher than that at E sites (4.96 mg/l) and G sites (5.18 mg/l). Mean zooplankton fresh-weight biomass was in the decreasing order of M (6.4 mg/l) > G (4.9 mg/l) > E (2.7 mg/l). However, Rotifera density was in the sequence of E > G > M. Both zooplankton biomass and phytoplankton biomass increased with the rise of TN and TP concentrations. Relationships between zooplankton biomass and phytoplankton biomass showed that zooplankton played a limited role in the control of algae in eutrophic lakes. Nutrient availability is much more important than zooplankton grazing pressure in controlling phytoplankton growth in lakes. For most sites in Lake Taihu, reduction of nutrient loading, as well as macrophyte conservation, zappears to be especially important in maintaining high water quality and regulating lake biological structure, but for M sites, it's urgent to control nutrient inputs rather than to restore macrophyte community. PMID- 17345010 TI - The application of satellite data for the quantification of mangrove loss and coastal management in the Godavari estuary, East Coast of India. AB - The mangrove formations of Godavari estuary are due to silting over many centuries. The estuary covers an area of 62,000 ha of which dense Coringa mangrove forest spread in 6,600 ha. Satellite sensor data was used to detect change in the mangrove cover for a period of 12 years (1992-2004). It was found that an area of about 1,250 ha of mangroves was destroyed by anthropogenic interference like aquaculture, and tree felling etc. It was found that mangrove's spectral response/digital number (DN) value is much lower than non-mangrove vegetation such as plantation and paddy fields in SWIR band. By taking this as an advantage, spectral data was utilized for clear demarcation of mangroves from nearby paddy fields and other vegetation. Simpson's diversity index, which is a measure of biodiversity, was found to be 0.09, showing mangroves dominance. Ecological parameters like mud-flats/swamps, mangrove cover alterations, and biodiversity status are studied in detail for a period of 12 years. The increase in mangrove front towards coast was delineated using remote sensing data. The major advantages of remote sensing data is monitoring of change periodically. The combination of moderate and high-resolution data provided detailed coastal land use maps for implementing coastal regulation measures. The classification accuracy has been achieved is 90%. Overall, simple and viable measures are suggested based on multi-spectral data to sustain this sensitive coastal ecology. PMID- 17345011 TI - Seasonal variation of some heavy metal pollution with environmental and microbiological parameters in sub-basin of Kocabas Stream (Biga, Canakkale, Turkey) by ICP-AES. AB - Waste water pollution in industrial areas is one of the most important environmental problems. Heavy metal pollution, especially chromium species in waste water sources from tannery affects our lives. Kocabas Stream is located in south-west Marmara region and Biga town is positioned in the sub basin on the stream. This water source functions as the water for irrigation in agriculture, drinking water for animals and for human use. Thus, this study is of great importance. Waste water pollution can affect all ecosystems and human health by directly or indirectly as in food chain. The concentration of heavy metals (Pb, Cd, Cu, Zn and Cr) were pre-analysed by ICP-AES method in water samples taken from sub-basin of Kocabas stream. In the results of these analyses, concentrations of the metals except chromium were founded at the limit value. But the total concentration of the Cr was found at high levels of between 0.0082 +/- 0.0001 and 5.7231 +/- 0.0921 mg l(-1) over the limit value (0.05 mg l(-1); WHO, EPA, TSE 266 and inland water quality classification) at sampling points very close to tannery factories. Also physicochemical and microbiological parameters of Kocabas Stream were determined. The effects of the experimental results on environment were investigated. PMID- 17345012 TI - Water quality assessment of Ogun river, South West Nigeria. AB - The quality of Ogun river in South-West, Nigeria was studied by a field survey for a period of 1 year (covering dry season and rainy season). Water samples were collected from thirteen sites and analysed for physico-chemical and bacteriological parameters as well as heavy metals using standard methods. Generally, the values obtained for turbidity, phosphate, oil and grease, iron and faecal coliform from all the sites in both seasons were above the maximum acceptable limit set by the World Health Organization (WHO) for drinking water. Also, the manganese content from all the sites in the dry season, lead concentrations from three sites in the dry season and cadmium concentrations from some sites in both seasons were above the WHO limit. The values obtained for total dissolved solids, dissolved oxygen and chloride at site M in the dry season and nitrate at site J in the rainy season were also above the WHO limit. Pollution of Ogun river water along its course is evidenced by the high concentrations of pollution indicators, nutrients and trace metals above the acceptable limit. This poses a health risk to several rural communities who rely on the river primarily as their source of domestic water. The study showed a need for continuous pollution monitoring programme of surface waters in Nigeria. PMID- 17345013 TI - Generation and quantification of hazardous dusts from coal mining in the Indian context. AB - The increasing trend of opencast coal mining in India tends to release huge amounts of dust. But there is no well-defined method of estimating dust emission due to different coal mining activities. This paper examines the sources of dust emission due to coal mining activities, and focuses on the quantification of dust emission with the development and use of emission factors. Because of their site specific nature, emission factors developed for one site may not give the correct results for another site. In the present investigation, prediction equations are utilized for the development of emission factors. For the applications of this concept, one large opencast coal project of Bharat Coking Coal Ltd. (BCCL) was investigated, and the total amount of dust emitted due to different mining activities was calculated by the utilization of emission factor data, which was estimated to be 9368.2 kg/day. This paper also focuses on the significance of this study in the field of environmental protection and likely impacts of such study. The paper concludes that once the amount of dust generation is estimated, the impact on air quality can be assessed appropriately and a proper air pollution control strategy can be developed. PMID- 17345014 TI - Sensitivity-optimized experiment for the measurement of residual dipolar couplings between amide protons. AB - High signal to noise is a necessity for the quantification of NMR spectral parameters to be translated into accurate and precise restraints on protein structure and dynamics. An important source of long-range structural information is obtained from (1)H-(1)H residual dipolar couplings (RDCs) measured for weakly aligned molecules. For sensitivity reasons, such measurements are generally performed on highly deuterated protein samples. Here we show that high sensitivity is also obtained for protonated protein samples if the pulse schemes are optimized in terms of longitudinal relaxation efficiency and J-mismatch compensated coherence transfer. The new sensitivity-optimized quantitative J correlation experiment yields important signal gains reaching factors of 1.5 to 8 for individual correlation peaks when compared to previously proposed pulse schemes. PMID- 17345015 TI - [Epidemiology of severe sepsis at a German university hospital]. AB - BACKGROUND AND PURPOSE: Sepsis still represents a major medical challenge despite several advances in therapy. Most published data on sepsis have been derived from clinical trials evaluating new drugs and from international cohort studies. The aim of this study was to analyze risk factors, mortality and causative pathogens in a cohort of unselected patients with severe sepsis at a German university hospital and to compare the data with international cohorts and recently published therapeutic trials. PATIENTS AND METHODS: Between May 1999 and December 2002, all patients of the surgical and internal medicine intensive care units of a university medical center with newly manifested severe sepsis and at least one organ failure were recruited into the prospective observational study "Unicenter Sepsis Survey Regensburg" (USSR). RESULTS: 182 patients were included. The median age of the patients studied was 58 years, the median SAPS II amounted to 42, mortality at day 14 and day 30 was 25% and 34%, respectively. 48% of the patients developed sepsis due to an internal disease, 33% after surgical emergency interventions, and 19% after planned surgical interventions. Patients with surgical emergencies had higher SAPS II values and a worse outcome. 35% of all patients developed acute renal failure. 85% of the patients were treated with vasopressors, and 90% had to be ventilated mechanically. 58% of the patients had a probable and 38% a confirmed focal infection; in the final retrospective analysis, an infectious genesis proved to be unlikely in 4% of the patients. CONCLUSION: The characteristics of unselected patients with severe sepsis at the authors' institution are comparable to data from recently published sepsis studies with respect to mortality, severity of disease, and range of causative pathogens. PMID- 17345017 TI - [Therapeutic management of acral manifestations of systemic sclerosis]. AB - Acral manifestations of systemic sclerosis include Raynaud's phenomenon, calcinosis cutis, and sclerodactyly. In the later stages of the disease, contractures of the skin and joints as well as obliterative vasculopathy leading to digital ulcers and necrotic lesions may occur. Patients with acral manifestations of systemic sclerosis are ideally treated by a team that includes a rheumatologist, dermatologist, hand surgeon, physiotherapist, and, eventually, a psychologist. Calcium channel antagonists, alpha(1)-adrenergic blockade with prazosin, and prostacyclin analogs were proven to be effective in the treatment of scleroderma-related Raynaud's phenomenon. Losartan, an angiotensin II receptor inhibitor, and fluoxetine, a selective serotonin reuptake inhibitor, have been beneficial for systemic sclerosis-associated Raynaud's phenomenon in pilot studies. Parenteral prostacyclin analogs, e. g., iloprost, can be recommended as first-line treatment of ischemic digital ulcers. When prostacyclin analogs fail, the phosphodiesterase type 5 inhibitor sildenafil can be tried to improve ulcer healing. Bosentan, an endothelin receptor antagonist, may prevent new digital ulcers. At present, there are no medical agents agreed to be generally effective in the reduction of calcinotic deposits or cutaneous fibrosis, although some drugs have been identified as potentially beneficial. Surgical treatment of acral manifestations consists of excision or curettage of symptomatic calcific deposits, digital sympathectomy, arterial reconstruction, and amputation in rare cases. Flexion contractures of the proximal interphalangeal joints, with secondary hyperextension of the metacarpophalangeal joints, can be treated by arthrodesis of the proximal interphalangeal joints and resection arthroplasty or prostheses at the metacarpophalangeal joints to improve hand function. PMID- 17345016 TI - [Hepatorenal syndrome. What's new in 2007?]. AB - BACKGROUND: Hepatorenal syndrome (HRS) is a serious complication of end-stage liver disease that was associated with a fatal prognosis in the past. A clear definition of HRS and increased understanding of the pathogenesis have led to considerable progress in therapy outcome. PATHOGENESIS: The major pathogenetic factor is vasodilation of the mesenteric circulation with arterial underfilling and consecutive renal vasoconstriction. THERAPY AND CONCLUSION: Restoration of an effective arterial blood volume can be achieved by the combination of vasopressor therapy (terlipressin, norepinephrine), in combination with volume expansion (albumin) with a success rate of up to 75%. Restoration of the effective arterial blood volume may also be achieved by implantation of a transjugular intrahepatic portosystemic stent (TIPS). This has also been successful in up to 50% of patients in selected cohorts. Finally, extracorporeal liver support systems based on exchange or detoxification of albumin have been successfully employed in a number of patients. Liver transplantation remains the only principal therapy of HRS as this is the single measure with a curative intent. All other forms of therapy are palliative but may serve as a bridge to liver transplantation. PMID- 17345018 TI - [Nephrology: renal transplantation]. AB - Renal transplantation is currently the best option for renal replacement therapy. Quality of life will improve and lifetime will extend compared to patients staying on dialysis. New findings in the fields of pathogenesis, diagnostics and treatment make renal transplantation an effective standard procedure. In Germany, there is an imbalance between available donor kidneys and recipients. The increasing waiting time is a challenge in the treatment of patients suffering from end-stage renal disease. In the last few years great efforts were undertaken to expand the donor pool. Problems are the unreadiness for organ donation on the one hand and extended indication for renal transplantation on the other hand. Transplantation of so-called marginal organs will implicate new problems. A main focus of further research is the chronic allograft nephropathy. Advances in the field of immunosuppressive treatment lead to better results in organ and patient survival. Individualization of immunosuppression becomes one of the most important points. New markers are necessary for monitoring. The aftercare in the transplant center in close collaboration with nephrologists and family doctors is essential for a successful transplantation. PMID- 17345019 TI - [IDEFICS: a multicenter European project on diet- and lifestyle-related disorders in children]. AB - The environment of children has drastically changed in Europe during the last decades as reflected in unhealthy dietary habits and a sedentary lifestyle. Nutrition obviously plays a part in the development of overweight and obesity in childhood. However, dietary factors and physical activity are also involved in the development of metabolic syndrome, diabetes, cardiovascular diseases, osteoporosis, and postural deformities like scoliosis. To stop the resulting epidemic of diet- and lifestyle-induced morbidity, efficient evidence-based approaches are needed. These issues are the focus of IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants), an Integrated Project within the 6th framework program of the European Commission. The IDEFICS consortium comprises 24 research centers and small or medium enterprises across Europe. One part of IDEFICS will investigate the etiology of selected diet- and lifestyle-related diseases in 2- to 10-year-old children. The impact of sensory perception and other internal and external triggers of children's food choices and consumer behavior will be studied in this context. Another part of IDEFICS will develop and evaluate strategies for the primary prevention of diet- and lifestyle-related diseases. The results of the project shall contribute to the development of harmonized European guidelines on diet and lifestyle for health promotion and disease prevention in children. PMID- 17345020 TI - [A problem of differential diagnosis: anemia of unknown origin]. PMID- 17345021 TI - [The German Program for Disease Management Guidelines Type 2 Diabetes - Diabetic Foot Guideline 2006. Short review]. AB - In Germany, the first national consensus between 14 medical scientific associations on evidence-based recommendations for prevention and therapy of foot problems in type 2 diabetes was reached in fall 2006. The recommendations' main sources are the NICE Guideline 2003 on foot problems in type 2 diabetes, as well as existing German guidelines and reviews of recent scientific evidence. The article gives an overview on authors, sources, and key recommendations of the German National Disease Management Guideline Type 2 Diabetes - Diabetic Foot 2006 (www.diabetes.versorgungsleitlinien.de). PMID- 17345022 TI - [Extraordinary manifestation of a gastric carcinoma by leptomeningeal carcinomatosis and spinal metastasis]. AB - BACKGROUND: Leptomeningeal carcinomatosis is a rare complication of solid tumors, e. g., breast, lung and gastrointestinal carcinomas. Clinical manifestations are variable with radicular pains with or without neurologic deficiencies as well as headache and hallucinations. CASE REPORT: The rare case of a 57-year-old patient with neurologic symptoms caused by a leptomeningeal carcinomatosis and a spinal metastasis of an asymptomatic signet-ring cell gastric carcinoma is reported. In spite of combined radiochemotherapy the patient died already 4 weeks after discharge from hospital due to an intracerebral hemorrhage. CONCLUSION: Until today, prognosis of leptomeningeal carcinomatosis is poor with a median survival between 3-4 months independently of the primary tumor. PMID- 17345023 TI - [Leydig cell tumor as a cause of hirsutism in a postmenopausal woman]. AB - BACKGROUND: Hirsutism or virilization in postmenopausal women may be due to increased testosterone levels caused by an androgen-secreting tumor. The preoperative localization of small ovarian or adrenal androgen-secreting tumors is difficult. CASE REPORT: A 61-year-old, postmenopausal woman presented with progressive hirsutism and deepening of voice over the last 9 years. Serum testosterone was very high (almost 30 nmol/l). Computed tomographic (CT) scans of the adrenals and ultrasonography of the pelvis were negative. Selective catheterization and [(18)F]FDG-PET/CT investigation raised the suspicion of an androgen-secreting tumor of the right ovary. Oophorectomy was performed, and a Leydig cell tumor of the right ovary was confirmed on histological examination. CONCLUSION: Selective catheterization and [(18)F]FDG-PET investigation may aid the detection of androgen-secreting tumors. PMID- 17345024 TI - Proximal interphalangeal joint replacement with pyrolytic carbon prostheses. AB - OBJECTIVE: Prosthetic joint replacement to reduce pain and maintain function of the proximal interphalangeal joint. INDICATIONS: Symptomatic arthritis of the proximal interphalangeal joint with preservation of the collateral ligaments, sufficient bone support, and intact or at least reconstructable extensor tendons. CONTRAINDICATIONS: Lack of stability, e. g., as a result of rheumatoid arthritis or destruction of the ligaments caused by an accident. Nonreconstructable extensor tendons. Florid or chronic infection. Lack of patient compliance. SURGICAL TECHNIQUE: Dorsal approach to the proximal interphalangeal joint. A triangular tendinous flap with pedicle, based distally on the insertion of the medial band, is lifted up, leaving the lateral bands intact. The joint surfaces are resected while maintaining the palmar plate and the collateral ligaments. The trial prosthesis is fitted, its position is checked, and the final unconstrained prosthetic components are inserted using a press-fit technique. The dorsal aponeurosis is reapproximated. RESULTS: 20 patients were treated for posttraumatic or idiopathic arthritis with 24 pyrolytic carbon PIP prostheses, and a follow-up examination was carried out after an average of 15 months (6-30 months). Surgical management was changed from arthroplasty to arthrodesis in three cases. For the remaining prostheses, an average range of motion of 50 degrees was achieved for the proximal interphalangeal joint. On the visual analog scale (VAS; 0: no pain, 10: incapacitating pain), the patients suffered few symptoms (VAS: 0-3). 80% of patients said they were satisfied with the outcome of the operation. In three cases (one infection, two dislocations) the prostheses had to be removed and arthrodesis performed. Migration of the distal components was observed on the radiographs in five cases, and of the proximal components in four cases, although this did not have any effect on the functional parameters. The development of a painless noise ("squeaking") was noticed in nine out of 21 prostheses. However, as with prosthetic migration, this did not cause any functional deficits. PMID- 17345025 TI - Stabilization of the posterior pelvic ring with a slide-insertion plate. AB - OBJECTIVE: Minimally invasive stabilization of the posterior pelvic ring in type C injuries. INDICATIONS: Unstable type C injuries of the pelvic ring, uni- or bilateral. - Transsymphyseal-transsacral instability. - Transpubic-transsacral instability. - Transsymphyseal-transsacroiliac instability. - Transpubic transsacroiliac instability. CONTRAINDICATIONS: Fractures in childhood. Comminuted fractures of the ilium. Patients with skin and soft tissues in a poor condition and/or local infection. Sacral fractures with a neurologic deficit are not a contraindication because they can be decompressed by distraction and stabilized in a neutral position by plate fixation. SURGICAL TECHNIQUE: Nut shaped osteotomy of the posterior superior iliac spine bilaterally through two short, vertical skin incisions. Tunneling through the muscles of the back to the opposite side. Length measurement for a 4.5-mm pelvic reconstruction plate. The plate is bent by about 70 degrees over the fourth lateral hole. Slide-insertion of the plate and bending of the free plate end for close fit. Cancellous bone screws are inserted into the plate holes. Refixation of the osteotomized bone fragments over the plate with small-fragment, cancellous bone screws. RESULTS: 34 patients with an average age of 42.6 years were treated according to the described method from 1998 to 2005; 18 were polytraumatized. The anterior pelvic ring was also stabilized by surgery in 28 patients for eleven of whom it was the first intervention in a two-stage procedure. 25 patients were available for clinical and radiologic follow-up at 17 months, on average. The plain radiographs after 1 year showed a very good outcome in 16 patients (maximal displacement of the posterior pelvic ring < 5 mm) and a good outcome in eight patients (displacement of 5-10 mm). In two patients there was loss of reduction in the 1st postoperative year despite a very good reduction result immediately postoperatively (dislocation < 5 mm), whereby the dislocation for one patient was < 10 mm on the final radiograph and 19 mm for the other. One patient presented with a late infection 11 weeks postoperatively that healed after implant removal and wound debridement. In two other patients, prominent screw heads, which were used for refixation of the osteotomized posterior superior iliac spine, had to be removed under local anesthesia in the 10th postoperative week. The further course for these two patients was uneventful. In one patient the implants were retrieved in the 5th postoperative month because the patient complained of internal hot and cold sensations although the soft tissue was not irritated. The plates were removed in six other cases after the fracture/instability had healed, i. e., after 9-12 months, on average; in all other cases the implants were left in situ. PMID- 17345026 TI - Modified transfemoral approach to revision arthroplasty with uncemented modular revision stems. AB - OBJECTIVE: Removal of a loose or fractured stem in total hip arthroplasty. Implantation and secure fixation of a modular uncemented revision stem to restore painless joint function. INDICATIONS: Loose and/or broken prosthetic stem. Risk of intraoperative fracture or perforation of the femur when stem revision becomes unavoidable. Periprosthetic fracture. CONTRAINDICATIONS: Loose prosthetic stems that can be revised without the risk of perforation or fracture of the femur. Interprosthetic femoral fractures between the ends of hip and knee prosthetic stems that require total replacement of the femur. SURGICAL TECHNIQUE: Exposure of the femur anterior to the lateral lip of the linea aspera in the lateral intermuscular septum. 3.2-mm drill holes are made at the anterior and posterior ends of the planned bone flap. Osteotomy of the femur anterior to the junction of the vastus lateralis and the gluteus medius muscles. Posterior osteotomy as well as distal transverse osteotomy between the drill holes and distal anterior osteotomy. The anterior osteotomy is performed using a chisel passed under the vastus lateralis from distal to proximal at the anterior aspect. The osteotomized lateral femoral bone flap with muscle attachment is folded back. Implantation of a modular uncemented revision stem and fixation of the bone flap with double cerclage. POSTOPERATIVE MANAGEMENT: Thrombosis prophylaxis, physiotherapy, gait training with partial loading of the limb at 10 kg for a period of 6 weeks with hip flexion limited to 70 degrees. Then, free range of movement and increased loading by 10 kg per week. RESULTS: 74 modular uncemented revision stems were implanted in transfemoral technique and the outcomes clinically and radiologically analyzed over an average follow-up period of 20.2 +/- 12.1 months (10-43 months). The Harris Hip Score increased from a preoperative value of 42.21 to 85.97 points after 2 years. Subsidence was observed for four stems and early loosening for two stems. The press-fit anchorage of these latter two stems was < 3 cm. PMID- 17345028 TI - Two-stage reimplantation with an application spacer and combined with delivery of antibiotics in the management of prosthetic joint infection. AB - OBJECTIVE: Management of a periprosthetic bacterial infection by two-stage revision of the prosthesis with implantation of an application spacer to maintain mobility and soft-tissue balance, and simultaneous delivery of antibiotics. INDICATIONS: Periprosthetic infection, acute and chronic infection caused by a spectrum of pathogens that are often resistant to treatment. Chronic course with fistula formation. Imminent loss of mobility due to protracted immobilization after implant removal. CONTRAINDICATIONS: Relative: acute infection caused by a known spectrum of pathogens that can be brought under control by synovectomy and antibiotic treatment or by one-stage revision. SURGICAL TECHNIQUE: First, a complete synovectomy is performed, and the implant components and all foreign material are removed. The implant bed is then prepared for implantation of the application spacer for antibiotics. Silicone catheters are advanced through two separate drill holes into the intramedullary canal and then inserted into the perforated implant stems. After the application spacer for antibiotics has been implanted, the wound is closed. POSTOPERATIVE MANAGEMENT: Daily doses of antibiotics are delivered through the percutaneous silicone catheters directly into the intramedullary canal at the site of the infection. The application spacer for antibiotics allows daily physiotherapy and mobilization on a continuous passive motion device. Partial weight bearing may even be allowed, if there is sufficient stability. TWO-STAGE, DEFINITIVE MANAGEMENT: Definitive treatment by implantation of the prosthesis is performed once the CRP (C-reactive protein) values have decreased to normal levels. RESULTS: 36 patients have been treated with this method since 1992. A two-stage revision procedure on a total knee was performed in 20 patients, and revision of a total hip 16 times. The longest postoperative follow-up period is now 10 years. To date, none of the joints treated according to this method have required revision surgery. After 6.1 years, range of motion at the knee joint is 0/0/106 degrees (Hospital of Special Surgery [HSS Score] 79.5); after 6.3 years, range of motion at the hip is 10/0/110 degrees (Harris Score 81.3). PMID- 17345027 TI - Uncemented femoral revision arthroplasty using the modular revision prosthesis MRP-TITAN revision stem. AB - OBJECTIVE: Restoration of a painless hip joint capable of bearing weight by uncemented implantation of a rotationally stable, modular revision stem anchored in the diaphysis. INDICATIONS: Prosthetic stem loosening with osteolytic bone defects (defect classification types I-III according to Paprosky). Material failure with broken prosthesis. Sub- and/or periprosthetic femoral fractures. Tumors. CONTRAINDICATIONS: Extensive osteolysis preventing diaphyseal anchorage of the prosthesis. SURGICAL TECHNIQUE: Transgluteal approach to the hip joint. Removal of the loose prosthetic stem and, if cemented, the bone cement as well. Excision of intramedullary granulation tissue. Reaming of the medullary cavity with flexible reaming shafts and form-fit, uncemented implantation of the star shaped modular revision stem with diaphyseal press fit. If there is extensive loss of metaphyseal bone stock, augmentation with autogenous/allogenic bone should be performed. POSTOPERATIVE MANAGEMENT: Mobilization on two underarm crutches from the 1st postoperative day. Removal of the Redon drains after 48 h. Partial loading with 20 kg for 6 weeks postoperatively. If plain radiographs show unchanged seating of the prosthesis after 6 weeks, loading can be increased by 10 kg per week until full weight bearing is achieved; thrombosis prophylaxis is continued throughout. Radiologic checkups after 3, 6, and 12 months. After that, the patient should be checked annually. RESULTS: 45 patients (n = 48 prostheses) with an average age of 67.2 years (min.-max. 42.4-87.4 years) were investigated. The average implantation time of the Modular Revision Prosthesis MRP-TITAN revision stem was 4.7 years (min.-max. 1.0-9.0 years). The Harris Hip Score for Paprosky bone defect types I-III had increased from 25.6 preoperatively to 71.4 postoperatively at the time of the final follow-up (< or = 0.05). Extensively defective bone was diagnosed preoperatively in 32 patients (> or = Paprosky IIB). Plain radiographs showed stable anchorage without migration in 44 patients. In one case, the stem (implantation time 2.36 years) was replaced due to increasing axial subsidence (> or = 5 mm). Good integration of bone graft with subsequent defect regeneration was seen in all patients with bone transplant (n = 30). Postoperative dislocation occurred in six patients and required closed reduction in four cases. Open reduction was performed in two patients, whereby the external rotation angle of the prosthetic neck was corrected without dismantling the distally anchored prosthetic stem components. The mechanical failure rate over the follow-up period of 9 years was one out of the 48 prospectively investigated prostheses. Rate of survival according to Kaplan-Meier was 97%. PMID- 17345029 TI - Correction of lateral tibial plateau depression and valgus malunion of the proximal tibia. AB - OBJECTIVE: Improvement of joint congruency in malunited lateral tibial plateau fractures, reduction of pain, prevention of osteoarthritis. INDICATIONS: Valgus malalignment of the proximal tibia combined with intraarticular depression of the tibial plateau. CONTRAINDICATIONS: Patients in poor general condition. Severe loss of knee function Elderly patients (> 65 years). Chronic infection. Soft tissue problems, Inability to perform non-weight bearing after the operation SURGICAL TECHNIQUE: Oblique osteotomy of the middle third of the fibula. Straight lateral or parapatellar approach to the lateral proximal tibia. Lateral arthrotomy of the knee joint. Proximal open wedge osteotomy of the tibia. Intraarticular correction of the depressed lateral tibial plateau through subchondral impaction of cancellous bone grafts. Evaluation of leg alignment. Interposition of bicorticocancellous bone grafts to maintain the open wedge osteotomy. Internal fixation, if necessary. POSTOPERATIVE MANAGEMENT: Continuous passive motion to 90 degrees of flexion from the 1st postoperative day. After application of a stabilizing brace, patients are allowed toe-touch weight bearing for 8 weeks. After radiologic bony healing has occurred, patients are allowed to increase weight bearing stepwise. RESULTS: Between 1977 and 1998, 23 patients were operated on. There were two failures resulting in one arthrodesis and one total knee arthroplasty. After an average of 14 years (5-26 years) 21 patients were followed up. Two patients suffered from severe progression of osteoarthritis after the osteotomy, four had some progression of cartilage degeneration, and 15 presented without changes in osteoarthritis. Mean difference in pre- and postoperative tibiofemoral angle was 8.6 degrees (range 13-4.4 degrees), mean difference in pre- and postoperative depression 6 mm (range 4-9 mm), and mean difference in pre- and postoperative range of motion 12 degrees (range 0-20 degrees). There were no nonunions. PMID- 17345032 TI - Strategies for achieving and monitoring myelin repair. AB - A number of factors more or less unique to multiple sclerosis have suggested that this disease may be particularly amenable to cell-based reparative therapies. The relatively focussed damage to oligodendrocytes and myelin at least in early disease implies that only a single population of cells need be replaced-and that the daunting problem of re-establishing connectivity does not apply. The presence of significant though partial spontaneous myelin repair in multiple sclerosis proves there to be no insurmountable barrier to remyelination intrinsic to the CNS: the therapeutic challenge becomes that of supplementing this spontaneous process, rather than creating repair de novo. Finally, the large body of available knowledge concerning the biology of oligodendrocytes, and the success of experimental myelin repair, have allowed cautious optimism that future prospects for such therapies are not unrealistic. Nonetheless, particular and significant problems are not hard to list: the occurrence of innumerable lesions scattered throughout the CNS, axon loss, astrocytosis, and a continuing inflammatory process, to name but a few. Here we review the progress and the areas where difficulties have yet to be resolved in efforts to develop remyelinating therapies for multiple sclerosis. PMID- 17345033 TI - Luigi Rolando (1773-1831). PMID- 17345034 TI - Posterior horn varicella-zoster virus myelitis. PMID- 17345035 TI - Polymorphisms in the neuromyelitis optica auto-antigen AQP4 and susceptibility to multiple sclerosis. PMID- 17345036 TI - Parietal proprioceptive loss with pseudoathetosis. PMID- 17345038 TI - Clinical and magnetic resonance imaging findings of HIV-negative patients with neurosyphilis. AB - There have been no serial studies about neuroradiological findings of neurosyphilis in the literature. There have been only case reports concerning HIV negative patients with neurosyphilis. We present 8 HIV negative neurosyphilis patients two of whom are women. The mean age of the patients was 48 years+/ 12.37. Five of the 8 patients had general paresis, two optic atrophy and one multiple cranial neuropathies. The CSF findings were quite similar in 6 of 8 patients. In half of the patients cranial MRI showed mild cerebral atrophy. Nonspecific hyperintense small foci in 3 patients are thought to be related to syphilis. Hyperintensity involving bilateral medial and anterior temporal regions more prominent on the left side was seen in one of the patients with general paresis. This finding may be due to cytotoxic edema associated with status epilepticus and may mimic herpes simplex and other limbic encephalitides. Though not typical, certain MRI findings guides for the diagnosis of neurosyphilis. PMID- 17345037 TI - Evolution of the diffusion-weighted signal and the apparent diffusion coefficient in the late phase after minor stroke: a follow-up study. AB - INTRODUCTION: Diffusion-weighted imaging (DWI) is mainly used in acute stroke, and signal evolution in the acute phase has been studied extensively. However, patients with a minor stroke frequently present late. Recent studies suggest that DWI may be helpful at this stage, but only very few published data exist on the evolution of the DW-signal in the weeks and months after a stroke. We performed a follow-up study of DWI in the late stages after a minor stroke. METHODS: 28 patients who presented 48 hours to 14 days after a minor stroke underwent serial MRI at baseline, 4 weeks, 8 weeks, 12 weeks, 6 months and>or=9 months after their event. Signal intensity within the lesion was determined on T2-weighted images, DW-images and the Apparent Diffusion Coefficient (ADC) map at each time-point, and ratios were calculated with contralateral normal values (T2r, DWIr, ADCr). RESULTS: T2r was increased in all patients from the beginning, and showed no clear temporal evolution. ADCr normalized within 8 weeks in 83% of patients, but still continued to increase for up to 6 months after the event. The DW-signal decreased over time, but was still elevated in 6 patients after>or=6 months. The evolution of ADCr and DWIr showed statistically highly significant inter individual variation (p<0.0001), which was not accounted for by age, sex, infarct size or infarct location. CONCLUSION: The ADC and the DW-signal may continue to evolve for several months after a minor ischaemic stroke. Signal evolution is highly variable between individuals. Further studies are required to determine which factors influence the evolution of the ADC and the DW-signal. PMID- 17345039 TI - Hyperhomocysteinemia is a risk factor of middle cerebral artery stenosis. AB - PURPOSE: Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for atherosclerosis. We aimed to determine the relation between Hcy and cerebral artery stenosis in a large Chinese population. METHODS: We present data concerning 2,500 residents. Plasma was saved from 1,020 residents who were asymptomatic. Hcy concentration was measured by fluorescence ration biochemical assay kit, and middle cerebral artery (MCA) was assessed by Transcranial Doppler in these subjects. RESULTS: Fifty-six residents with MCA stenosis were included in this study. The remained 964 residents without stenosis were control. Analysis of the data revealed that the plasma concentration of Hcy (18.33+/-5.34 micromol/L), age (63.9+/-12.9) and systolic pressure (142.6+/-22.6 mmHg) in the stenotic group were increased (p<0.0001) compared with the control group (Hcy12.95+/-4.57 micromol/L, age 55.8+/-10.9, systolic pressure 126.3+/-20.3 mmHg). Based on logistic regression, 5 factors emerged as independent predictors of MCA stenosis: Hcy (OR=1.16, 95%confidence interval 1.14-1.26), male (OR=2.63, 95%CI 1.49-4.66), age (OR=1.04, 95%CI 1.01-1.07), hypertension (OR=9.16, 95%CI 4.57-18.35), diabetes mellitus (OR=5.90, 95%CI 3.09-11.29). CONCLUSION: Hyperhomocysteinemia might be one of the risk factors for cerebral artery stenosis. It may play a role in atherosclerosis and thrombosis. PMID- 17345040 TI - Right temporal cerebral dysfunction heralds symptoms of acute mountain sickness. AB - Acute mountain sickness (AMS) can occur during climbs to high altitudes and may seriously disturb the behavioral and intellectual capacities of susceptible subjects. During a Himalayan expedition 32 mountaineers were examined with electroencephalography (EEG) and transcranial doppler sonography (TCD) to assess relative changes of middle cerebral artery velocity in relation to end-expiratory CO2 (EtCO2), peripheral saturation (SaO2), and symptoms of AMS. We tested the hypothesis that O2 desaturation and EtCO2 changes precede the development of AMS and result in brain dysfunction and compensatory mechanisms which can be measured by EEG and TCD, respectively. Contrary to our hypothesis, we found that subjects who later developed symptoms of AMS between 3,440 m and 5,050 m altitude exhibited an increase of slow cerebral activity in the right temporal region already at 3,440 m. Cerebral blood flow increased in these mountaineers in the right middle cerebral artery at 5,050 m. These findings indicate that regional brain dysfunction, which can be documented by EEG, heralds the appearance of clinical symptoms of AMS. PMID- 17345041 TI - APOE genotypes in Greek multiple sclerosis patients: no effect on the MS Severity Score. PMID- 17345042 TI - Open label, multicenter, 28-week extension study of the safety and tolerability of memantine in patients with mild to moderate Alzheimer's disease. AB - BACKGROUND: Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be safe and to have beneficial effects on cognition, function, behavior, and global patient status in patients with Alzheimer's disease (AD) in studies lasting 3-6 months. It is approved in the U.S. and Europe for the treatment of moderate to severe AD and is currently under investigation for mild to moderate AD. OBJECTIVE: To evaluate the long-term safety of memantine in patients with mild to moderate AD and to investigate the tolerability of once daily dose administration. METHODS: This 28-week study enrolled 314 patients with mild to moderate AD who had completed a 24-week, double-blind, placebo-controlled lead-in clinical trial of memantine in AD. Following an 8-week double-blind dose titration phase (used to assess the tolerability of different dosing regimens), subjects were assigned to continuous open label memantine (10 mg, bi.d.) treatment for 20 weeks. Safety outcome measures included treatment-emergent adverse events (AEs), deaths, vital signs, electrocardiograms, and laboratory parameters. RESULTS: During the 28-week study (Phase A+Phase B), the most common AEs were falls and other injuries (both 10.8%). AEs resulted in treatment discontinuation in 6.7% of patients. Discontinuations due to AEs were similar in the once-daily dosing groups compared to the twice-daily dosing groups. During dose titration, completion rates were greater than 90% for both groups. Conversion to once-daily dosing in patients already receiving twice-daily doses of memantine was also well tolerated. CONCLUSIONS: Memantine monotherapy in patients with mild to moderate AD is safe and well tolerated for at least one year. Once-daily dosing during titration and short-term maintenance therapy is safe and well tolerated. PMID- 17345043 TI - Presenilin 2 Ser130Leu mutation in a case of late-onset "sporadic" Alzheimer's disease. PMID- 17345044 TI - Increased sensory thresholds in a patient with Ross syndrome: a case report. PMID- 17345045 TI - Clinical-diffusion mismatch defined by NIHSS and ASPECTS in non-lacunar anterior circulation infarction. AB - OBJECTIVES: Instead of the mismatch in MRI between the perfusion-weighted imaging (PWI) lesion and the smaller diffusion-weighted imaging (DWI) lesion (PWI-DWI mismatch), clinical-DWI mismatch (CDM) has been proposed as a new diagnostic marker of brain tissue at risk of infarction in acute ischemic stroke. The Alberta Stroke Program Early CT Score (ASPECTS) has recently been applied to detect early ischemic change of acute ischemic stroke. The present study applies the CDM concept to DWI data and investigated the utility of the CDM defined by the NIH Stroke Scale (NIHSS) and ASPECTS in patients with non-lacunar anterior circulation infarction. METHODS: Eighty-seven patients with first ever ischemic stroke within 24 hours of onset with symptoms of non-lacunar anterior circulation infarction with the NIHSS score>or=8 were enrolled. Initial lesion extent was measured by the ASPECTS on DWI within 24 hours, and initial neurological score was measured by the NIHSS. As NIHSS>or=8 has been suggested as a clinical indicator of a large volume of ischemic brain tissue, and the majority of patients with non-lacunar anterior infarction with score of NIHSS<8 had lesions with ASPECTS>or=8 on DWI, so CDM was defined as NIHSS>or=8 and DWI-ASPECTS 8>or=. We divided patients into matched and mismatched patient groups, and compared them with respect to background characteristics, neurological findings, laboratory data, radiological findings and outcome. RESULTS: There were 35 CDM-positive patients (P group, 40.2%) and 52 CDM-negative patients (N group , 59.8%). P group patients had a higher risk of early neurological deterioration (END) than N group patients (37.1% vs 13.5%, p<0.05), which were always accompanied by lesion growth defined by 2 or more points decrease on ASPECTS (36 to 72 hours after onset on CT). The NIHSS at entry were significantly lower in the P group, but there was no difference in the outcome at three months measured by the modified Rankin Scale. However, CDM was not an independent predictor of END by multiple logistic regression analysis. CONCLUSIONS: Patients with CDM had high rate of early neurological deterioration and lesion growth. CDM defined as NIHSS>or=8 and DWI ASPECTS>or=8 can be another marker for detecting patients with tissue at risk of infarction, but more work is needed to clarify whether this CDM method is useful in acute stroke management. PMID- 17345046 TI - Detailed electroencephalographic long-term follow-up study in Lewy body dementia with periodic sharp wave complexes. PMID- 17345047 TI - Effects of somatosensory stimulation on motor function in chronic cortico subcortical strokes. AB - Somatosensory stimulation enhances aspects of motor function in patients with chronic, predominantly subcortical infarcts. We investigated the effects of somatosensory stimulation on motor function in stroke patients with predominantly cortical involvement in the middle cerebral artery territory in a double-blind, pseudorandomized crossover trial. Motor performance was evaluated with the Jebsen Taylor test before, after 2-hour somatosensory stimulation, and after subsequent motor training (n=11). In one experimental session, patients were submitted to median nerve stimulation (MNS) and in the other session, to control stimulation (CS). The order of the sessions was counterbalanced across patients. Improvement in performance in the Jebsen-Taylor test after somatosensory stimulation and after motor training was significantly greater in the MNS session than in the CS session. Additionally, patients who received MNS in the second session maintained the beneficial effects of training 30 days later. A single MNS session improves hand motor function in patients with chronic cortico-subcortical strokes and appears to favor consolidation of training effects. Somatosensory stimulation may be an adjuvant tool for stroke rehabilitation in patients with cortical lesions. PMID- 17345048 TI - Neurological and functional recovery in human stroke are associated with peripheral blood CD34+ cell mobilization. AB - BACKGROUND: A spontaneous mobilization of Peripheral Blood-Mononuclear CD34+ Cells (PB-MNC-CD34+) has recently been reported in human myocardial infarction and found to be related to improved heart function and survival. However, nothing is known regarding a possible relation between PB-MNC-CD34+ mobilization and neurological recovery in human acute cerebral ischemia. METHODS AND RESULTS: PB MNC-CD34+ were determined daily after an acute cerebral ischemic attack for 14 days in 25 patients with acute ischemic stroke and compared with controls. Results indicated that stroke was followed by large and bursting mobilizations of PB-MNC-CD34+. The amplitude of the mobilizations was similar to those observed in Granulocyte Colony Stimulating Factor (G-CSF) conditioned aplastic patients following myeloablative therapy before leukapheresis and autologous bone graft. The extent of PB-MNC-CD34+ mobilization in each patient was directly related to neurological and functional recoveries as assessed by NIH Stroke Scale, and modified Rankin Scale respectively. CONCLUSIONS: The mobilization of PB-MNC-CD34+ cells might be predictive of neurological and functional recovery. PMID- 17345049 TI - Study of cerebral cavernous malformation in Spain and Portugal: high prevalence of a 14 bp deletion in exon 5 of MGC4607 (CCM2 gene). AB - OBJECTIVE: We aimed to study clinical, radiological and molecular genetic features of patients with cerebral cavernous malformations (CCMs) from the Iberian Peninsula. METHODS: We screened Krit1(CCM1), MGC4607(CCM2), and PDCD10(CCM3) by systematic SSCP and direct sequencing of coding exons in 48 nuclear families and 30 sporadic cases of CCM from Spain and Portugal. RESULTS: Screening of CCM patients detected nine different mutations in 19 families. We found four new mutations in Krit1. Three of them were caused by either a small insertion or deletion, which lead to frameshift and premature termination codons. We also found a missense L308H mutation located in a highly conserved sequence within the ankyrin domain of Krit1. In CCM2, we found a redundant 14 bp deletion in exon 5 of MGC4607 which predicts a truncated protein at residue 230. We did not find mutations in CCM3. CONCLUSIONS: Finding that the 14 bp deletion was present in eleven families from the Iberian Peninsula indicates a high prevalence of this mutation. This redundant CCM2 mutation is worth considering in molecular diagnosis and genetic counselling of cerebral cavernous malformations. PMID- 17345050 TI - Joint effects of risk factors for stroke and transient ischemic attack in a German population: the EPIC Potsdam Study. AB - BACKGROUND: Single, modifiable risk factors for stroke have extensively been studied. In contrast, differences of their combined effects among stroke and transitoy ischemic attack (TIA) have been rarely investigated. The aim of the present study was to assess single and joint effects of risk factors on the incidence of stroke and TIA and to compare their magnitudes in a large population based German cohort. METHODS: Incident cases of stroke and TIA were identified among 25,538 participants (aged 35-65 at baseline) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Relative risks for stroke and TIA related to modifiable risk factors were estimated using Cox proportional hazard models. RESULTS: During 4.3 years of follow-up 100 stroke cases and 112 TIA cases occurred. Incidences of stroke and TIA were 91.7 and 102.7 per 100,000 person-years, respectively. Relative risks for ischemic stroke (RR 5.12, 95% CI 1.49-17.6, p for trend<0.0001) and for TIA (RR 3.08, 95% CI 1.00 9.44, p for trend<0.024) were highest among participants having 4 or 5 modifiable risk factors. 58.5% of ischemic strokes and 26.2% of TIA cases were attributable to the 5 risk factors hypertension, diabetes mellitus, high alcohol consumption, hyperlipidemia, and smoking. CONCLUSION: Our data indicate that classical risk factors may explain almost 60% of ischemic stroke but only one in four TIA cases. Analysing potential differences of known risk factors between ischemic stroke and TIAs and the identification of other determinants of ischemic attacks are important steps to better explain the burden of stroke. PMID- 17345052 TI - Neck pain in chronic whiplash syndrome treated with botulinum toxin. A double blind, placebo-controlled clinical trial. AB - OBJECTIVES: Neck pain in chronic whiplash syndrome is a major burden for patients, healthcare providers and insurance companies. Randomized data on treatment of botulinum toxin in chronic whiplash syndrome are scarce. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin for neck pain in chronic whiplash syndrome. METHODS: 40 patients with chronic whiplash syndrome (whiplash associated disorders grade 1 and 2) were randomly assigned to receive botulinum toxin (maximum 100 units) or placebo (saline) in muscles with increased tenderness. RESULTS: After 12 weeks there was no significant difference between the two treatment groups in decrease of neck pain intensity on VAS (-7.0 mm, 95% confidence interval (CI) [-20.7 to +6.7]), mean number of neck pain days (-1%; 95% CI [-15% to +13%]), neck pain hours per day (-0.14; 95% CI [-3.0 to +2.7]), days on which symptomatic treatment was taken (-0.7%; 95% CI [-15% to +13%]) number of analgesics taken per day (-0.14; 95% CI [-0.6 to +0.4]) and total cervical range of motion (-11 degrees; 95% CI [-40 to +17]). There also was no significant difference in patient's assessment of improvement after week 4, 8 and 12. CONCLUSIONS: Botulinum toxin was not proven effective in treatment of neck pain in chronic whiplash syndrome. Increased muscle tenderness alone might not be the major cause of neck pain in whiplash syndrome. PMID- 17345051 TI - Outcome prediction in acute monohemispheric stroke via magnetoencephalography. AB - BACKGROUND: Following an ischemic stroke a highly variable clinical outcome is commonly evident despite similar onset symptoms as well as lesion characteristics. The aim of this study was to identify indexes providing early prediction of functional recovery, in addition to clinical severity and lesion dimension at onset of stroke. METHODS: In 32 patients, magnetoencephalographic (MEG) parameters collected in the acute phase (<10 days from symptoms onset, T0) from affected (AH) and unaffected (UH) hemispheres at rest and evoked by sensory stimuli were evaluated in association with the clinical outcome in a stabilized phase (T1, median 7.8 months) classified with three levels: worsening, partial and full recovery. RESULTS: Multiple multinomial logistic regression indicated AH gamma and UH delta band powers able to prognosticate clinical outcome at T1. After inclusion in this analysis, lesion volume had the strongest predictive ability, and UH delta band power remained as a predictive factor with a measurable cut-off, maximizing both sensitivity and specificity of the prediction: a patient with UH delta below cut-off would recover to some extent; a patient with UH delta above cut-off would have a probability of about 70% to worsen. CONCLUSIONS: MEG UH delta and AH gamma band powers were found to provide useful information about long-term outcome prognosis. Only the increase of delta band activity in the unaffected hemisphere contains information about the outcome in addition to the lesion volume. PMID- 17345053 TI - is leukoaraiosis on CT an accurate surrogate marker for the presence of microbleeds in acute stroke patients? AB - Microbleeds (MB) detected on gradient echo magnetic resonance images (GRE) are a potential risk factor for intracerebral hemorrhage after thrombolysis or oral anticoagulation. We assessed whether the presence of MB could be predicted from the extent of white matter disease (WMD) on computed tomography (CT). METHODS: We studied consecutive TIA or ischemic stroke patients who presented to the ER and who underwent both CT and GRE. WMD was rated on CT using a three point scale by two independent observers. The presence of MB was assessed on GRE. Logistic regression was used to predict the presence of MB on GRE. RESULTS: 199 consecutive patients underwent both CT and GRE. MB were identified on GRE in 56 patients (28.1%). After adjustment for age and sex, MB were more frequent in patients with leukoaraiosis (OR 2.8 per 1-point increase on the Van Swieten scale, p<0.001) and in patients presenting with a lacunar or posterior circulation syndrome (OR 2.0, p=0.048). The area under the ROC-curve derived from the logistic model was 0.70 (95% CI 0.61-0.79). Age, sex, hypertension, diabetes or the presence of left ventricular hypertrophy on ECG were not different in patients with or without MB. CONCLUSION: White matter disease on CT is associated with the presence of microbleeds on GRE. However, leukoaraiosis does not detect the presence of MB accurately enough to be considered a surrogate marker. PMID- 17345054 TI - Leg blood flow measurements using venous occlusion plethysmography during head-up tilt. AB - We tested whether venous occlusion plethysmography (VOP) is an appropriate method to measure calf blood flow (CBF) during head-up tilt (HUT). CBF measured with VOP was compared with superficial femoral artery blood flow as measured by Doppler ultrasound during incremental tilt angles. Measurements of both methods correlated well (r = 0.86). Reproducibility of VOP was fair in supine position and 30 degrees HUT (CV: 11%-15%). This indicates that VOP is an applicable tool to measure leg blood flow during HUT, especially up to 30 degrees HUT. PMID- 17345056 TI - Token mediated tool exchange between tufted capuchin monkeys (Cebus apella). AB - Three experiments were conducted to test whether a pair of tufted capuchin monkeys (Cebus apella) could generalize their ability to exchange tokens and tool objects with a human experimenter to similar exchanges with a conspecific partner. Monkeys were tested in side-by-side enclosures, one enclosure containing a tool-use apparatus and one or more token(s), and the other enclosure containing one or more tool object(s). The monkeys willingly transferred tokens and tools to a conspecific with little practice. Following a small amount of training, we also found that the monkeys would select situation-appropriate tokens to exchange for specific tools, but did not select appropriate tool objects in response to another monkey's token transfers. Implications regarding role reversal are discussed. PMID- 17345055 TI - [Steroids for reduction of morbidity following tonsillectomy]. AB - BACKGROUND: Of the morbidities that follow tonsillectomy, nausea and vomiting, fever, pain and inadequate oral intake are the most commonly encountered. The incidence of postoperative nausea and vomiting (PONV) has been reported as between 40% and 85%. In children, the risk of dehydration is increased owing to the delay in oral intake of fluids in the early postoperative period. In efforts to reduce postoperative morbidity, numerous modifications and adjuncts to the surgical procedure have been suggested, including the use of steroids. PATIENTS AND METHODS: Reduction in PONV, pain and early return to a normal diet were studied as separate end-points in a review of the current literature. RESULTS: A total of 31 studies matched our search criteria and involved paediatric and adult patient populations. Only 15 studies evaluated pain, PONV and diet. The lack of standardised surgical and anaesthetic techniques and the variations in length of follow-up, concentration of steroids administered and patient age distribution weaken the impact of the results recorded in several studies. However, two-thirds show that a single intravenous dose of dexamethasone reduces pain, although this was limited to the early postoperative period. Moreover, 15 studies confirmed a beneficial effect of dexamethasone on both PONV and early oral intake. CONCLUSIONS: Preoperative administration of a single dose of dexamethasone to reduce postoperative morbidity resulting from tonsillectomy is supported by several studies. Adverse events have never been reported. However, further studies are warranted to determine the optimum dose required and the effect in adult tonsillectomy patients. In addition, the data should be based on standardised surgical and anaesthetic techniques to allow reliable evaluation of the significance of all outcome measures. PMID- 17345057 TI - High frequency of Panton-Valentine leukocidin genes in invasive methicillin susceptible Staphylococcus aureus strains and the relationship with methicillin resistant Staphylococcus aureus in Cordoba, Argentina. AB - In the study presented here, the genetic characteristics of methicillin susceptible Staphylococcus aureus (MSSA) strains isolated from patients attending hospitals in the city of Cordoba, Argentina, during 1999-2002 were evaluated to determine their genetic relationship with methicillin-resistant S. aureus (MRSA) clones as part of an effort to control the potential emergence of new epidemic MRSA strains. The results showed there is a high frequency of MSSA strains carrying Panton-Valentine leukocidin genes in invasive infections in Cordoba, Argentina, particularly in those occurring in hospital settings. Panton-Valentine leukocidin genes were found in the genomic background of one clone (ST30-N pulsotype) belonging to a successful internationally distributed MSSA lineage (clonal complex 30), which is closely related to the EMRSA-16 pandemic clone. These genes were also detected in the ancestral clone (ST5-M pulsotype) of the most prevalent MRSA epidemic clone causing healthcare-associated infections in this region, known as the Cordobes/Chilean clone. The molecular characterization of circulating MSSA strains, including the detection of Panton-Valentine leukocidin genes, is thus a useful marker for investigating the evolving epidemiology of hospital- and community-acquired MRSA clones. PMID- 17345058 TI - Conditions controlling the onset of breeding migration of the Japanese mountain stream frog, Rana sakuraii. AB - I studied the conditions controlling the timing of breeding migration of the Japanese mountain stream frog Rana sakuraii, an explosive breeder, over 9 years (1992, 1993 and 1999-2005). I analysed two factors: the daily cumulative temperature (DCT) during hibernation and the triggering temperature on the day of migration onset. Frogs hibernated in shallow running water in streams in December. A total of 53,155 breeding migrating adults were captured by traps. Every year, breeding migration was induced by a rise in daily maximum water temperature to about 5 degrees C. However, its date was limited to 1 February at the earliest, and the onset needed a DCT (from 20 January, using 3 degrees C as the threshold for daily effective temperature) of at least about 15 degrees C. Earlier (e.g. in mid- or late January), even if the maximum temperature rose to 5 8 degrees C, migration did not begin. Moreover, even in early February, if the maximum temperature rose to 5 degrees C, if it had been too cold in January and the DCT was low, migration would not begin until mid- or late February. Thus, the earliest date of readiness for migration varied from 1 February to mid-February, depending on the winter DCT. Logistic regression analyses showed that both factors, the DCT and the daily temperature, were significant. I propose that in temperate-zone amphibian explosive breeders, both the passing of an essential number of days and an essential DCT during hibernation are prerequisites for the onset of breeding migration before the daily temperature rises to the threshold. PMID- 17345059 TI - Single nucleotide polymorphisms in rye (Secale cereale L.): discovery, frequency, and applications for genome mapping and diversity studies. AB - To elucidate the potential of single nucleotide polymorphism (SNP) markers in rye, a set of 48 barley EST (expressed sequence tag) primer pairs was employed to amplify from DNA prepared from five rye inbred lines. A total of 96 SNPs and 26 indels (insertion-deletions) were defined from the sequences of 14 of the resulting amplicons, giving an estimated frequency of 1 SNP per 58 bp and 1 indel per 214 bp in the rye transcriptome. A mean of 3.4 haplotypes per marker with a mean expected heterozygosity of 0.66 were observed. The nucleotide diversity index (pi) was estimated to be in the range 0.0059-0.0530. To improve assay cost effectiveness, 12 of the 14 SNPs were converted to a cleaved amplified polymorphic sequence (CAPS) format. The resulting 12 SNP loci mapped to chromosomes 1R, 3R, 4R, 5R, 6R, and 7R, at locations consistent with their known map positions in barley. SNP genotypic data were compared with genomic simple sequence repeat (SSR) and EST-derived SSR genotypic data collected from the same templates. This showed a broad equivalence with respect to genetic diversity between these different data types. PMID- 17345060 TI - A high density barley microsatellite consensus map with 775 SSR loci. AB - A microsatellite or simple sequence repeat (SSR) consensus map of barley was constructed by joining six independent genetic maps based on the mapping populations 'Igri x Franka', 'Steptoe x Morex', 'OWB(Rec) x OWB(Dom)', 'Lina x Canada Park', 'L94 x Vada' and 'SusPtrit x Vada'. Segregation data for microsatellite markers from different research groups including SCRI (Bmac, Bmag, EBmac, EBmag, HVGeneName, scsssr), IPK (GBM, GBMS), WUR (GBM), Virginia Polytechnic Institute (HVM), and MPI for Plant Breeding (HVGeneName), generated in above mapping populations, were used in the computer program RECORD to order the markers of the individual linkage data sets. Subsequently, a framework map was constructed for each chromosome by integrating the 496 "bridge markers" common to two or more individual maps with the help of the computer programme JoinMap 3.0. The final map was calculated by following a "neighbours" map approach. The integrated map contained 775 unique microsatellite loci, from 688 primer pairs, ranging from 93 (6H) to 132 (2H) and with an average of 111 markers per linkage group. The genomic DNA-derived SSR marker loci had a higher polymorphism information content value (average 0.61) as compared to the EST/gene derived SSR loci (average 0.48). The consensus map spans 1,068 cM providing an average density of one SSR marker every 1.38 cM. Such a high-density consensus SSR map provides barley molecular breeding programmes with a better choice regarding the quality of markers and a higher probability of polymorphic markers in an important chromosomal interval. This map also offers the possibilities of thorough alignment for the (future) physical map and implementation in haplotype diversity studies of barley. PMID- 17345061 TI - Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach. AB - AIMS/HYPOTHESIS: In the present study we investigated potential associations of a set of 45 single nucleotide polymorphisms (SNP) in 20 candidate genes on eight chromosomes with diabetic nephropathy (DN) in type 2 diabetes mellitus. We aimed to compare two methodological approaches suitable for analysing susceptibility to complex traits: single- and multi-locus analyses. MATERIALS AND METHODS: The study comprised a total of 647 subjects in one of three groups: diabetes with or without DN, or no diabetes. Genotypes were detected by PCR-based methodology (PCR only, PCR plus RFLP, or allele-specific PCR). Haplotypes were inferred in silico. Set association (tested using SUMSTAT software) was used for multilocus analysis. RESULTS: After correction for multiple comparisons, only one SNP, in the gene encoding the receptor of advanced glycation end products, AGER 2184A/G (gene symbol formerly known as RAGE) showed a significant association with DN (p = 0.0006) in single-locus analysis. In multi-locus analysis, six SNPs exhibited a significant association with DN: four SNPs on chromosome 6p (AGER 2184A/G, LTA 252A/G, EDN1 8002G/A and AGER -429T/C) and two SNPs on chromosome 7q (NOS3 774C/T and NOS3 E298D), omnibus p = 0.033. Haplotype analysis revealed significant differences between DN and control groups in haplotype frequencies on chromosome 6 (p = 0.0002); however, there were no significant difference in the frequencies of the NOS3 haplotypes on chromosome 7. Logistic regression analysis identified SNPs AGER 2184A/G and NOS3 774C/T, together with diabetes duration and HbA1c, as significant predictors of DN. Testing for interactions between SNPs on chromosomes 6 and 7 did not provide significant evidence for epistatic interaction. CONCLUSIONS/INTERPRETATION: Using the set-association approach we identified significant associations of several SNPs on chromosomes 6 and 7 with DN. The single- and multi-locus analyses represent complementary methods. PMID- 17345062 TI - Phosphylated tyrosine in albumin as a biomarker of exposure to organophosphorus nerve agents. AB - The organophosphorus nerve agents sarin, soman, cyclosarin and tabun phosphylate a tyrosine residue on albumin in human blood. These adducts may offer relatively long-lived biological markers of nerve agent exposure that do not 'age' rapidly, and which are not degraded by therapy with oximes. Sensitive methods for the detection of these adducts have been developed using liquid chromatography-tandem mass spectrometry. Adducts of all four nerve agents were detected in the blood of exposed guinea pigs being used in studies to improve medical countermeasures. The tyrosine adducts with soman and tabun were detected in guinea pigs receiving therapy 7 days following subcutaneous administration of five times the LD(50) dose of the respective nerve agent. VX also forms a tyrosine adduct in human blood in vitro but only at high concentrations. PMID- 17345063 TI - Protective effects of ibuprofen on testicular torsion/detorsion-induced ischemia/reperfusion injury in rats. AB - The aim of this study was to investigate the protective effect of ibuprofen on testicular torsion/detorsion-induced ischemia/reperfusion (I/R) injury. A total of 48 prepubertal male Wistar albino rats were divided into two models: early and late orchiectomy. Testicular torsion was created by rotating the right testis 720 degrees in a clockwise direction. The ischemia period was 5 h and orchiectomy was performed after 5 h of detorsion in the early orchiectomy model (EOM). In the late orchiectomy model (LOM), the ischemia period was 5 h and orchiectomy was performed after 7 days of detorsion. In the EOM, ibuprofen (70 mg/kg, po) was administrated only once, 40 min prior to detorsion. In the LOM, ibuprofen (70 mg/kg, po) was administered 40 min before detorsion, once daily for 7 days. Bilateral orchiectomy was performed in all groups to measure the tissue levels of malondialdehyde (MDA) and to microscopically investigate light and electrons. The presence of endothelial nitric oxide synthase (eNOS) activity was shown with immunohistochemical studies. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in ipsilateral and contralateral testis when both early and late I/R groups were compared to the sham groups. Furthermore, ibuprofen-treated animals showed an improved histological appearance in both models of testicular torsion. Ibuprofen treatment prevented lipid peroxidation resulting in decreased MDA accumulation in the testes of both models. After I/R, eNOS immunoreactivity was increased in the testicular tissues. Ibuprofen treatment decreased eNOS immunoreactivity in the germ cells of the tubules in the contralateral testes, but intense eNOS immunoreactivity was shown in the ipsilateral testes of the LOM. Electron microscopy of the testes of rats demonstrated that ibuprofen pretreatment was particularly effective in preventing the mitochondrial degeneration in both Sertoli and spermatid cells in the LOM. Because of its anti-inflammatory and antioxidant effects, ibuprofen pretreatment may have protective effects in the experimental testicular torsion/detorsion model in rats. PMID- 17345064 TI - Effects of topiramate on cue-induced cigarette craving and the response to a smoked cigarette in briefly abstinent smokers. AB - RATIONALE: Clinical studies have shown that topiramate, an anticonvulsant medication, may be effective as a treatment for smoking cessation. However, less is known about topiramate effects on nicotine withdrawal and craving and its interactions with a smoked cigarette. OBJECTIVES: The objective of this study was to investigate the effects of topiramate treatment on abstinence-related nicotine withdrawal, cue-induced cigarette craving, and the acute effects of a smoked cigarette. MATERIALS AND METHODS: Fifteen female and 25 male cigarette smokers were randomly assigned to 9-day treatment with topiramate (final titration dose, 75 mg/day) or placebo. On the last day of treatment, after a 3-h smoke-free abstinence period, participants were evaluated for symptoms of nicotine withdrawal and then underwent cigarette and neutral cue reactivity testing. Thirty minutes after completing cue exposure testing, participants were then evaluated for the acute effects of a smoked cigarette. Cue reactivity and acute smoking measures included subjective ratings of cigarette craving and withdrawal and physiological measures of skin conductance and temperature, heart rate, and blood pressure. In addition, smoking topography was measured using a puff volume apparatus. RESULTS: Topiramate treatment enhanced subjective ratings of withdrawal after the 3-h abstinence period and reduced pre-cue skin conductance levels. Cigarette cue exposure resulted in a moderate increase in craving, which was unaffected by treatment. Topiramate treatment enhanced the rewarding effects of a smoked cigarette, even while participants smoked less per puff and achieved lower plasma nicotine levels. CONCLUSION: Results suggest that topiramate enhances both nicotine withdrawal and reward. These findings question the utility of topiramate treatment for smoking cessation. PMID- 17345067 TI - Assessment of chemical purity of 10B-enriched p-boronophenylalanine by high performance liquid chromatography coupled on-line with inductively coupled plasma optical emission spectrometry. AB - A dual-detection technique, consisting of a combination of reversed-phase high performance liquid chromatography and on-line detection of elemental boron in the column effluents by inductively coupled plasma optical emission spectrometry, was tested for drug analysis. The method was applied to assessing the chemical purity of p-boronophenylalanine (BPA), isotopically enriched in 10B. This compound is employed as a fructose complex solution for biodistribution studies in laboratory and clinical trials of boron neutron capture therapy. Besides the determination of the content of BPA, required for chemical quality controls of solutions of the complex used for infusions, resolution of mixtures of BPA and two usually accompanying residual impurities (phenylalanine and tyrosine) was achieved with UV detection. The limits of detection (in solution) were 1.5 and 0.6 ng ml-1, respectively. In addition, by monitoring a sensitive-element emission wavelength it was possible to jointly observe the elution of boron-containing compounds that may be transparent to UV radiation or to confirm the presence of boron in potential impurities accompanying the drug. Those impurities may arise from the BPA synthesis or may be produced by degradation during the aging of the solutions. Chromatographic peaks corresponding to the amino acids and also to a related inorganic compound were detected in BPA-fructose complex solutions that were stored for different times and under different conditions. An increase in the areas of the peaks attributed to tyrosine and phenylalanine was observed for BPA-fructose solutions stored refrigerated for 1 month to 1 year, suggesting that degradation processes able to reduce the amount of bioavailable BPA could be active. PMID- 17345065 TI - Ethanol-MDMA interactions in rats: the importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination. AB - RATIONALE: In our previous work, we showed that ethanol (EtOH) potentiates 3,4 methylenedioxymethamphetamine (MDMA)-induced hyperlocomotion while protecting against its hyperthermic effects. Whereas the effect on activity were found on all days (although declining over the three first days), the protection against hyperthermia completely disappeared on the second day. The latter effect was previously thought to reflect tolerance to ethanol or the combination, per se. OBJECTIVE: In the present study, we changed the treatment regimen to irregular and longer intervals between treatments (48, 120, and again 48 h) to check if tolerance was still observed. RESULTS: We found progressive sensitization of locomotor activity to EtOH (1.5 g/kg, i.p.)+MDMA (6.6 mg/kg, i.p.), and a partial EtOH protection against MDMA-induced hyperthermia that persisted after the first drug challenge day. When the monoamine neurotransmitters, dopamine, and serotonin were assessed 2 weeks after treatment, we found no consistent effect on the concentration of any of these neurotransmitters, whatever the treatment. Similarly, we found that regional brain concentrations of MDMA were not significantly affected by EtOH at a 45-min post-treatment delay; however, the overall ratio of the metabolite 3,4-methylenedioxyamphetamine (MDA) to MDMA was lower (overall, -16%) in animals treated with the combination compared to MDMA alone, indicating possible contribution of pharmacokinetic factors. This difference was especially marked in the striatum (-25%). CONCLUSIONS: These findings shed new light on the consequences of EtOH-MDMA, taken together at a nearly normal ambient temperature, both in terms of motivation and potential risks for recreational drug users. PMID- 17345066 TI - 14-Methoxymetopon, a highly potent mu opioid agonist, biphasically affects ethanol intake in Sardinian alcohol-preferring rats. AB - RATIONALE: Increased opioidergic activity is thought to increase the propensity to consume ethanol. However, the dose monotonicity and receptor subtype for this effect remain uncertain. 14-methoxymetopon is a centrally acting, selective micro opioid receptor agonist with greater systemic antinociceptive potency than morphine and a putatively improved therapeutic index. OBJECTIVE: To determine whether 14-methoxymetopon influenced voluntary ethanol intake in Sardinian alcohol-preferring (sP) rats. METHODS: Male sP rats with continuous 2-bottle choice access to ethanol (10% v/v) or water were subjects. The effects of systemic 14-methoxymetopon administration (2, 5, 12.25, 30 micro/kg, s.c.) on 4-h ethanol intake were determined. The ability of naltrexone (50 micro/kg, s.c.), an opioid antagonist, to block actions of 14-methoxymetopon (12.25, 30 micro/kg, s.c.) was examined as were the effects of 14-methoxymetopon (12.25 micro/kg, s.c.) on self-administered blood alcohol levels (BALs) and clearance of a passive ethanol bolus (1 g/kg). Finally, the effects of central 14-methoxymetopon administration (0.0003-100 ng, i.c.v.) on 4-h ethanol intake were evaluated. RESULTS: Systemic 14-methoxymetopon very potently and dose-dependently suppressed ethanol and food intake for 30 min, followed by a greater, longer-lasting, and behaviorally specific increase in ethanol intake. The increased ethanol intake led to threefold higher BALs, was naltrexone-reversible, and not due to altered ethanol clearance. Intracerebroventricular 14-methoxymetopon administration rapidly altered ethanol intake per an inverted U-shaped dose-response function, increasing it at a 10 pg dose, while suppressing it at a 10,000-fold higher dose. CONCLUSIONS: The novel mu analgesic increases ethanol intake, a potential therapeutic liability, and results suggest a non-monotonic influence of brain mu opioid receptor stimulation on ethanol intake. PMID- 17345068 TI - Integrated microfluidic device with an electroplated palladium decoupler for more sensitive amperometric detection of the 8-hydroxy-deoxyguanosine (8-OH-dG) DNA adduct. AB - 8-hydroxy-deoxyguanosine (8-OH-dG) DNA adduct is one of the most frequently used biomarkers reporting on the oxidative stress that leads to DNA damage. More sensitive and reliable microfluidic devices are needed for the detection of these biomarkers of interest. We have developed a capillary electrophoresis (CE)-based microfluidic device with an electroplated palladium decoupler that provides significantly improved detection limit, separation efficiency, and resolving power. The poly(dimethylsiloxane) (PDMS)/glass hybrid device has fully integrated gold microelectrodes covered in situ with palladium nanoparticles using an electroplating technique. The performance and coverage of the electrodes electroplated with palladium particles were evaluated electrochemically and via scanning electron microscope (SEM) imaging, respectively. The performance of the device was tested and evaluated with different buffer systems, pH values, and electric field strengths. The results showed that this device has significantly improved resolving power, even at separation electric field strengths as high as 600 V cm-1. The detection limit for the 8-OH-dG adduct is about 20 attomoles; the concentration limit is on the order of 100 nM (S/N=3). A linear response is reported for both 8-OH-dG and dG in the range from 100 nM to 150 microM (approximately 100 pA microM-1) with separation efficiencies of approximately 120,000-170,000 plates m-1. PMID- 17345069 TI - Navigating a scientific job market and how the library can help. PMID- 17345070 TI - Mechanical ion gate for electrospray-ionization ion-mobility spectrometry. AB - A novel ion gate for electrospray-ionization atmospheric-pressure ion-mobility spectrometry (ESI-IMS) has been constructed and evaluated. The ion gate consisted of a chopper wheel with two windows--one for periodic ion passage from the ESI source into the drift region and the other for timing and synchronization purposes. The instrument contained a 45.0 cm long drift tube comprising 78 stainless steel rings (0.12 cm thick, 4.90 cm o.d., 2.55 cm i.d.). The rings were connected together in series with 3.34-MOmega resistors. The interface plate and the back plate were also connected with the first and the last rings, respectively, of the drift tube with 3.34-MOmega resistors. A potential of -20.0 kV was applied to the back plate and the interface plate was grounded. The drift tube was maintained at an electric field strength of approximately 400 V cm-1. An aperture grid was attached to the last ring in front of a Faraday plate detector, center-to-center. Several sample solutions were electrosprayed at +5.0 kV with +500 V applied to the ion gate. Baseline separations of selected benzodiazepines, antidepressants, and antibiotics were observed with moderate experimental resolution of approximately 70. PMID- 17345072 TI - No effect of the CYP1A2*1F genotype on thioridazine, mesoridazine, sulforidazine plasma concentrations in psychiatric patients. PMID- 17345071 TI - Dopaminergic influences on changes in human tactile acuity induced by tactile coactivation. AB - As shown in animal experiments, dopaminergic mechanisms participate in N-methyl-D aspartate (NMDA) receptor-dependent neuroplasticity. Dopamine is thought to play a similar role in humans, where it influences learning and memory. Here, we tested the dopaminergic action on learning in the tactile domain. To induce tactile non-associative learning, we applied a tactile coactivation protocol, which is known to improve tactile two-point discrimination of the stimulated finger. We studied the influence of a single oral dose of levodopa (25, 50, 100, 250 or 350 mg) administered preceding the coactivation protocol on changes in tactile performance in different groups of subjects. In addition, 3 x 100 mg levodopa was administered over a time period of 3 h in another group. Under placebo conditions, tactile two-point discrimination was improved on the coactivated index finger. Similar improvement was found when 25, 50 and 250 mg levodopa was applied. On the contrary, tactile improvement was completely eliminated by 1 x 100 and 3 x 100 mg levodopa. No drug effects were found on the left index finger indicating that the drug had no effect on performance per se. In contrast to previous findings in the motor and speech domain, we found that the administration of levodopa exerts either no or even negative effects on non associative learning in the human somatosensory system. Whenever levodopa is used in neurorehabilitative context, it has to be kept in mind that beneficial effects in the motor or speech domain cannot be easily generalized to other systems. PMID- 17345073 TI - Effect of efavirenz on the pharmacokinetics of ketoconazole in HIV-infected patients. AB - OBJECTIVE: To investigate the effect of efavirenz on the ketoconazole pharmacokinetics in HIV-infected patients. METHODS: Twelve HIV-infected patients were assigned into a one-sequence, two-period pharmacokinetic interaction study. In phase one, the patients received 400 mg of ketoconazole as a single oral dose on day 1; in phase two, they received 600 mg of efavirenz once daily in combination with 150 mg of lamivudine and 30 or 40 mg of stavudine twice daily on days 2 to 16. On day 16, 400 mg of ketoconazole was added to the regimen as a single oral dose. Ketoconazole pharmacokinetics were studied on days 1 and 16. RESULTS: Pretreatment with efavirenz significantly increased the clearance of ketoconazole by 201%. C(max) and AUC(0-24) were significantly decreased by 44 and 72%, respectively. The T ((1/2)) was significantly shorter by 58%. CONCLUSION: Efavirenz has a strong inducing effect on the metabolism of ketoconazole. PMID- 17345074 TI - Linking preclinical and clinical whole-body physiologically based pharmacokinetic models with prior distributions in NONMEM. AB - PURPOSE: The aim of this study was to evaluate the performance of the NONMEM prior functionality compared to a full Bayesian method when applied to population physiological models using diazepam as a case study. METHODS: Whole-body physiologically based pharmacokinetic (WBPBPK) models for diazepam were initially developed, tested and calibrated for rats and man using a full Bayesian analysis as implemented in WINBUGS: . The final models were implemented in NONMEM and the results from the two analyses compared in terms of parameter estimates, measures of parameter precision and run times. RESULTS: NONMEM population parameter estimates were in close agreement with those produced by the Bayesian analysis although there was a substantial shortening of run time for both the animal WBPBPK model (4.5 vs. 21 h) and human WBPBPK models (2 vs. 167 h). The adequacy of the model and the final parameter estimates were judged to be sufficient by the model's ability to describe individual tissue concentration-time profiles. The model provided a good overall description of the plasma concentration-time data in both rat and man with comparable parameter precision. A limited nonparametric bootstrap (n = 50) was performed to assess parameter sensitivity, bias and imprecision. No systematic bias was seen when comparing bootstrap means to final parameter estimates. CONCLUSIONS: The ease of implementation and reductions in run time hopefully provide a further step forward in allowing the wider use of these complex and information-rich models together with clinical data in the future. PMID- 17345075 TI - Cerebral vasculitis: imaging signs revisited. AB - Inflammatory stenoses of cerebral blood vessels, although rare in general, are an important cause of cerebral ischemia in younger patients. The diagnosis is often difficult. The first step in the diagnostic process is the identification of brain lesions consistent with cerebral vasculitis. Brain lesions are frequently found in this patient group, especially if modern imaging tools such as diffusion and perfusion-weighted imaging are employed. Although no specific pattern for this entity exists, multiple infarcts of various ages in more than one vascular territory should raise this suspicion. The next step in the imaging of patients with suspected vasculitis is the demonstration of the underlying vascular pathology. MR angiography is the mainstay of investigating patients for intracranial vascular stenoses. However, at 1.5 T it is only diagnostic for stenoses of large brain arteries. Hence, conventional angiography is still required to investigate stenoses of medium and small-sized brain arteries. Recent work suggests that MRI can directly demonstrate mural thickening and contrast enhancement in basal brain arteries, rendering biopsy obsolete in this patient group. A classification for cerebral vasculitis is proposed according to the size of the affected brain vessels, analogous to the pertinent nomenclature of primary systemic vasculitis. PMID- 17345076 TI - MR-based imaging of neural stem cells. AB - The efficacy of therapies based on neural stem cells (NSC) has been demonstrated in preclinical models of several central nervous system (CNS) diseases. Before any potential human application of such promising therapies can be envisaged, there are some important issues that need to be solved. The most relevant one is the requirement for a noninvasive technique capable of monitoring NSC delivery, homing to target sites and trafficking. Knowledge of the location and temporospatial migration of either transplanted or genetically modified NSC is of the utmost importance in analyzing mechanisms of correction and cell distribution. Further, such a technique may represent a crucial step toward clinical application of NSC-based approaches in humans, for both designing successful protocols and monitoring their outcome. Among the diverse imaging approaches available for noninvasive cell tracking, such as nuclear medicine techniques, fluorescence and bioluminescence, magnetic resonance imaging (MRI) has unique advantages. Its high temporospatial resolution, high sensitivity and specificity render MRI one of the most promising imaging modalities available, since it allows dynamic visualization of migration of transplanted cells in animal models and patients during clinically useful time periods. Different cellular and molecular labeling approaches for MRI depiction of NSC are described and discussed in this review, as well as the most relevant issues to be considered in optimizing molecular imaging techniques for clinical application. PMID- 17345077 TI - Tamm-Horsfall protein in recurrent calcium kidney stone formers with positive family history: abnormalities in urinary excretion, molecular structure and function. AB - Tamm-Horsfall protein (THP) powerfully inhibits calcium oxalate crystal aggregation, but structurally abnormal THPs from recurrent calcium stone formers may promote crystal aggregation. Therefore, increased urinary excretion of abnormal THP might be of relevance in nephrolithiasis. We studied 44 recurrent idiopathic calcium stone formers with a positive family history of stone disease (RCSF(fam)) and 34 age- and sex-matched healthy controls (C). Twenty-four-hour urinary THP excretion was measured by enzyme linked immunosorbent assay. Structural properties of individually purified THPs were obtained from analysis of elution patterns from a Sepharose 4B column. Sialic acid (SA) contents of native whole 24-h urines, crude salt precipitates of native urines and individually purified THPs were measured. THP function was studied by measuring inhibition of CaOx crystal aggregation in vitro (pH 5.7, 200 mM sodium chloride). Twenty-four-hour urine excretion of THP was higher in RCSF(fam) (44.0 +/- 4.0 mg/day) than in C (30.9 +/- 2.2 mg/day, P = 0.015). Upon salt precipitation and lyophilization, elution from a Sepharose 4B column revealed one major peak (peak A, cross-reacting with polyclonal anti-THP antibody) and a second minor peak (peak B, not cross-reacting). THPs from RCSF(fam) eluted later than those from C (P = 0.021), and maximum width of THP peaks was higher in RCSF(fam )than in C (P = 0.024). SA content was higher in specimens from RCSF(fam) than from C, in native 24-h urines (207.5 +/- 20.4 mg vs. 135.2 +/- 16.1 mg, P = 0.013) as well as in crude salt precipitates of 24-h urines (10.4 +/- 0.5 mg vs. 7.4 +/- 0.9 mg, P = 0.002) and in purified THPs (75.3 +/- 9.3 microg/mg vs. 48.8 +/- 9.8 microg/mg THP, P = 0.043). Finally, inhibition of calcium oxalate monohydrate crystal aggregation by 40 mg/L of THP was lower in RCSF(fam) (6.1 +/- 5.5%, range -62.0 to +84.2%) than in C (24.9 +/- 6.0%, range -39.8 to +82.7%), P = 0.022, and only 25 out of 44 (57%) THPs from RCSF(fam )were inhibitory (positive inhibition value) vs. 25 out of 34 (74%) THPs from C, P < 0.05. In conclusion, severely recurrent calcium stone formers with a positive family history excrete more THP than healthy controls, and their THP molecules elute later from an analytical column and contain more SA. Such increasingly aggregated THP molecules predispose to exaggerated calcium oxalate crystal aggregation, an important prerequisite for urinary stone formation. PMID- 17345078 TI - Imaging features of posterior mediastinal chordoma in a child. AB - A 5 1/2-year-old boy presented with repeated episodes of stridor and cough. Chest radiography demonstrated a widened mediastinum. Evaluation by CT revealed a low density posterior mediastinal mass initially diagnosed as benign tumor. Histopathological analysis of the resected mass disclosed a malignant chordoma. Our radiological results are described with an analysis of the imaging findings in the medical literature. We present our suggestions for preoperative evaluation of posterior mediastinal tumors. PMID- 17345079 TI - Model-free analysis of binding at lipid membranes employing micro-calorimetric measurements. AB - Based on universal thermodynamic principles (Schwarz in Biophys Chem 86:119-129, 2000) it is shown how measured enthalpy changes can be utilized to determine the relevant binding isotherm as well as the variation of the molar enthalpy change. This is carried out in a novel way involving multiple titration experiments whose evaluation requires no beforehand assumptions or models whatever. An appropriate specific model mechanism may be discussed afterwards and developed in view of the given experimental results. The pertinent procedure is demonstrated using micro calorimetric data obtained in the case of the local anesthetic dibucaine as it associates with POPC liposomes. Mutual interactions of the bound ligand molecules could be described in terms of repulsive enthalpic and entropic activity coefficients. Apparently these are induced by electrostatic forces and by the finite size of binding sites, respectively. PMID- 17345080 TI - Cofactor regeneration in phototrophic cyanobacteria applied for asymmetric reduction of ketones. AB - The obligate photoautotrophic cyanobacterium Synechococcus PCC7942 and the photoheterotrophic heterocystous cyanobacterium Noctoc muscorum are able to reduce prochiral ketones asymmetrically to optical pure chiral alcohols without light. An example is the synthesis of S-pentafluoro(phenyl-)ethanol with an enantiomeric excess >99% if 2'-3'-4'-5'-6'-pentafluoroacetophenone is used as substrate. If no light is available for regeneration of the cofactor nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH), glucose is used as cosubstrate. Membrane disintegration during asymmetric reduction promotes cytosolic energy generating metabolic pathways. Observed regulatory effects depicted by an adenosine triphosphate (ATP) to nicotinamide adenine dinucleotide phosphate (oxidized form) (NADP(+)) ratio of 3:1 for efficient cofactor recycling indicate a metabolization via glycolisis. The stoichiometric formation of the by product acetate (1 mol acetate/1 mol chiral alcohol) indicates homoacetic acid fermentation for cofactor regeneration including the obligate photoautotrophic cyanobacterium Synechococcus PCC7942. PMID- 17345081 TI - Plant-growth-promoting compounds produced by two agronomically important strains of Azospirillum brasilense, and implications for inoculant formulation. AB - We evaluated phytohormone and polyamine biosynthesis, siderophore production, and phosphate solubilization in two strains (Cd and Az39) of Azospirillum brasilense used for inoculant formulation in Argentina during the last 20 years. Siderophore production and phosphate solubilization were evaluated in a chemically defined medium, with negative results. Indole 3-acetic acid (IAA), gibberellic acid (GA(3)), and abscisic acid (ABA) production were analyzed by gas chromatography mass spectrometry. Ethylene, polyamine, and zeatin (Z) biosynthesis were determined by gas chromatography-flame ionization detector and high performance liquid chromatography (HPLC-fluorescence and -UV), respectively. Phytohormones IAA, Z, GA(3), ABA, ethylene, and growth regulators putrescine, spermine, spermidine, and cadaverine (CAD) were found in culture supernatant of both strains. IAA, Z, and GA(3) were found in all two strains; however, their levels were significantly higher (p < 0.01) in Cd (10.8, 2.32, 0.66 microg ml(-1)). ABA biosynthesis was significantly higher (p < 0.01) in Az39 (0.077 microg ml(-1)). Ethylene and polyamine CAD were found in all two strains, with highest production in Cd cultured in NFb plus L-methionine (3.94 ng ml(-1) h(-1)) and Az39 cultured in NFb plus L-lysine (36.55 ng ml(-1) h(-1)). This is the first report on the evaluation of important bioactive molecules in strains of A. brasilense as potentially capable of direct plant growth promotion or agronomic yield increase. Az39 and Cd showed differential capability to produce the five major phytohormones and CAD in chemically defined medium. This fact has important technological implications for inoculant formulation as different concentrations of growth regulators are produced by different strains or culture conditions. PMID- 17345082 TI - Construction of a novel synergistic system for production and recovery of secreted recombinant proteins by the cell surface engineering. AB - We determined whether the cocultivation of yeast cells displaying a ZZ-domain and secreting an Fc fusion protein can be a novel tool for the recovery of secreted recombinant proteins. The ZZ-domain from Staphylococcus aureus protein A was displayed on the cell surface of Saccharomyces cerevisiae under the control of the GAL1 promoter. Strain S. cerevisiae BY4742 cells displaying the ZZ-domain on their surface were used for cocultivation with cells that produce a target protein fused to the Fc fragment as an affinity tag. The enhanced green fluorescent protein or Rhizopus oryzae lipase was genetically fused to the N and C termini of the Fc fragment of human immunoglobulin G, respectively. Through analysis by fluorescence-activated cell sorting and enzymatic assay, it was demonstrated that these fusion proteins are successfully produced in the medium and recovered by affinity binding with the cell surface displaying the ZZ-domain. These results suggest that the ZZ-domain-displaying cell and Fc fusion protein secreting cell can be applied to use in synergistic process of production and recovery of secreted recombinant proteins. PMID- 17345083 TI - Large scale deletions in the Saccharomyces cerevisiae genome create strains with altered regulation of carbon metabolism. AB - Saccharomyces cerevisiae, for centuries the yeast that has been the workhorse for the fermentative production of ethanol, is now also a model system for biological research. The recent development of chromosome-splitting techniques has enabled the manipulation of the yeast genome on a large scale, and this has allowed us to explore questions with both biological and industrial relevance, the number of genes required for growth and the genome organization responsible for the ethanol production. To approach these questions, we successively deleted portions of the yeast genome and constructed a mutant that had lost about 5% of the genome and that gave an increased yield of ethanol and glycerol while showing levels of resistance to various stresses nearly equivalent to those of the parental strain. Further systematic deletion could lead to the formation of a eukaryotic cell with a minimum set of genes exhibiting appropriately altered regulation for enhanced metabolite production. PMID- 17345084 TI - Murine toxicology and pharmacokinetics of novel retinoic acid metabolism blocking agents. AB - PURPOSE: Novel potent C-4 azolyl retinoic acid metabolism blocking agents (RAMBAs)-VN/14-1, VN/50-1, VN/66-1, VN/67-1, and VN/69-1, have been synthesized and investigated for their in vitro and in vivo effects against breast and prostate cancers. These RAMBAs, in addition to being potent inhibitors of all trans-retinoic acid (ATRA) metabolism have potent anti-cancer properties and in vivo anti-tumor efficacies as characterized in breast and prostate cancer models. Here we determined the toxicity and pharmacokinetics (PK) of these various RAMBAs. METHODS: Preliminary acute toxicity studies of these RAMBAs were carried out using Swiss NIH mice. The toxicity profile of the RAMBAs was evaluated relative to ATRA. Three different doses (8.3, 33, and 100 micromol/kg/day) of ATRA and RAMBAs were administered on a daily basis subcutaneously for 14 days to the mice. Clinical signs of toxicity alopecia, scaly skin, and loss of body weight in the mice were observed during the study and the maximum tolerated dose was determined. PK of selected agents (VN/14-1, VN/50-1, and VN/66-1) was studied in Balb/C mice after a single dose subcutaneous administration. Plasma concentrations of the agents were quantitatively determined using a high performance liquid chromatographic method with ultraviolet detection. Plasma concentration versus time profiles were fit to various PK structural models and relevant PK parameters were estimated. RESULTS: VN/66-1 and VN/69-1 were found to be the least toxic even at the highest doses when compared to the other RAMBAs and ATRA. VN/66-1 had the longest half-life, the slowest clearance, and the greatest exposure. CONCLUSIONS: Based on PK characteristics and toxicity studies, VN/66-1 appeared to be the most favorable agent. However, both VN/14-1 and VN/66 1 are our leads based on the fact that VN/14-1 has been found to be highly effective in endocrine-sensitive and -resistant breast cancer cells and tumors with little toxicity. Our findings provide valuable information that will be used to select RAMBAs and establish therapeutic regimens that provide optimal efficacy with minimal toxicity. PMID- 17345085 TI - A phase I study of bi-weekly administration of 24-h gemcitabine followed by 24-h irinotecan in patients with solid tumors. AB - PURPOSE: To determine the maximal tolerated doses (MTD) and dose-limiting toxicities (DLT) of combination of 24-h infusions of gemcitabine and irinotecan in patients with advanced solid tumors. PATIENTS AND METHODS: Twenty-four patients with advanced solid tumors received gemcitabine as a 24-h IV infusion followed by a 24-h infusion of irinotecan every 2 weeks. Pharmacokinetic parameters of both drugs and their metabolites were estimated by using non compartmental methods. RESULTS: Twenty-four patients were fully evaluable for toxicity. DLT was observed in two of six patients at irinotecan/gemcitabine 110/150 mg/m(2) (grade 3 diarrhea and grade 3 GI bleeding). No patient developed acute cholinergic symptoms at any dose. Other toxicities were < or =grade 2 nausea, vomiting, and fatigue. Tumor responses were observed in three patients (one CR: cholangiocarcinoma; two PR: SCLC, gastric neuroendocrine tumor). Stable disease >3 months was found in six patients including five patients who had failed short infusions of either drug. Pharmacokinetic analysis showed that C (max) of each drug and active metabolites were dose-dependent. High dose of gemcitabine increased C (max), AUC, and T(1/2) of irinotecan. However, gemcitabine had minimal effects on SN-38. CONCLUSIONS: The recommended dose for Phase II studies is gemcitabine 125 mg/m(2) given as a 24-h IV infusion on D1 and D15, followed by a 24-h IV infusion of irinotecan 110 mg/m(2) on D2 and D16. Both pretreated patients and chemo-naive patients seem to tolerate higher doses of this combination without significant toxicities. Objective responses among patients with solid tumors, in particular cholangiocarcinoma and small cell lung cancer merits further investigation. PMID- 17345086 TI - Flavonoids inhibit breast cancer resistance protein-mediated drug resistance: transporter specificity and structure-activity relationship. AB - PURPOSE: ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-related protein 1 (MRP1), confer resistance to various anticancer agents. We previously reported that some flavonoids have BCRP-inhibitory activity. Here we show the reversal effects of an extensive panel of flavonoids upon BCRP-, P-gp-, and MRP1-mediated drug resistance. METHODS: Reversal effects of flavonoids upon BCRP-, P-gp-, or MRP1-mediated drug resistance were examined in the BCRP- or MDR1-transduced human leukemia K562 cells or in the MRP1-transfected human epidermoid carcinoma KB-3-1 cells using cell growth inhibition assays. The IC(50) values were determined from the growth inhibition curves. The RI(50) values were then determined as the concentration of inhibitor that causes a twofold reduction of the IC(50) in each transfectant. The reversal of BCRP activity was tested by measuring the fluorescence of intracellular topotecan. RESULTS: The BCRP-inhibitory activity of 32 compounds was screened, and 20 were found to be active. Among these active compounds, 3',4',7-trimethoxyflavone showed the strongest anti-BCRP activity with RI(50) values of 0.012 microM for SN-38 and 0.044 muM for mitoxantrone. We next examined the effects of a panel of 11 compounds on P-gp- and MRP1-mediated drug resistance. Two of the flavones, 3',4',7-trimethoxyflavone and acacetin, showed only low anti-P-gp activity, with the remainder displaying no suppressive effects against P-gp. None of the flavonoids that we tested inhibited MRP1. CONCLUSION: Our present results thus indicate that many flavonoids selectively inhibit BCRP only. Moreover, we examined the structure-BCRP inhibitory activity relationship from our current study. PMID- 17345087 TI - Circulating biomarkers for prostate cancer. AB - Due to its significant applicability for early detection, risk prediction and follow-up evaluation, prostate specific antigen (PSA) has revolutionized our ability to treat prostate cancer patients. With the prevalent use of PSA for early detection during the last two decades, disease characteristics have been altered towards early detected, localized tumors with a high chance of cure following local therapy. This advantage faces the risk of overdetection and overtreatment. In addition, PSA lacks both, sensitivity and specificity to accurately detect patients at risk of prostate cancer. Therefore, novel biomarkers are urgently needed to improve identification of men at risk of having the disease and to predict the natural behaviour of the tumor. Recent advances in the evaluation of high-throughput technologies have led to the discovery of novel candidate markers for prostate cancer. This article will briefly discuss current PSA-based strategies and review several novel biomarkers for prostate cancer, detectable in blood. PMID- 17345088 TI - Re-oxygenation of haemoglobin in livores after post-mortem exposure to a cold environment. AB - When a body is exposed to a cold environment, the livid colour of livor mortis changes to cherry red. This colour change is due to an increase in the concentration of oxygenated haemoglobin. The chronological course and the extent of haemoglobin re-oxygenation associated with the exposure to low ambient temperatures have not been understood so far. The relations between refrigeration time under a constant ambient temperature (5 degrees C), skin temperature, body mass index (BMI), spectral reflectance curve and O2-Hb concentration in livor mortis were systematically investigated in 84 bodies brought to the Institute of Legal Medicine of the Freiburg University Hospital shortly after death. In the first measurements performed shortly after death, the reflectance curves of the livores of all bodies showed a broad minimum at 555 nm. After a refrigeration time of 44.9 +/- 17.9 h, the spectrum changed to the typical picture of O2-rich blood with 2 minima at 541 and 576 nm and a maximum at 560 nm in between. This qualitative change of the reflectance spectra was observed for a skin temperature of 10.3 +/- 2.7 degrees C. With the help of a physical skin model it was possible to calculate that due to the post-mortem exposure to cold the O2-Hb concentration in the livores rose from 0-1% to a value of up to 89.3%. The change in the reflectance curve was discernible from an oxygen saturation of 25 +/- 13.8%. PMID- 17345089 TI - Effect of shortening the barrel in contact shots from rifles and shotguns. AB - In a suicidal gunshot fired to the chest from a carbine, the barrel of which had been shortened to half its original length, an unexpectedly large degree of destruction of the anterior thoracic wall with extensive undermining of the subcutis was found. This phenomenon was investigated for reconstructive purposes by firing test shots from two different long guns (caliber 7.92 x 57 repeating rifle with full-jacketed pointed bullet and caliber 12/70 single-barreled shotgun with shotgun slug) into blocks of soap (38 x 25 x 25 cm). The contact shots were fired before and after shortening the barrels (repeating rifle from 60 to 30 cm and single-barreled shotgun from 72 to 36 cm). The volume of the cavities in the simulant was visualized three-dimensionally with the help of a multislice computed tomography (CT) scanner and calculated sectionally. With the repeating rifle and the single-barreled shotgun, the shots from the sawed-off barrels produced significantly larger cavity diameters in the first section of the bullet track. This effect is attributable to the fact that, with a shortened barrel, the gas pressure at the muzzle is higher, thus, leading to increased expansion in the initial part of the wound track in contact shots. PMID- 17345090 TI - Intravitreal bevacizumab (Avastin) for subretinal neovascularization secondary to type 2A idiopathic juxtafoveal telangiectasia. AB - BACKGROUND: To evaluate the efficacy and safety of intravitreal bevacizumab (Avastin) in the treatment of subretinal neovascularization (SRNV) secondary to type 2A idiopathic juxtafoveal telangiectasia (IJT). METHODS: Intravitreal bevacizumab (1.25 mg/0.05 ml) was injected as primary treatment into six eyes of six patients with SRNV due to IJT in this nonrandomized, interventional case series. The best-corrected visual acuity (BCVA) was measured and the optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) findings were examined before and after treatment. The patients were followed up for 3-6 months. RESULTS: Pre-injection BCVA measured 20/400 to 20/120 (mean 20/200). After a mean follow-up of 4.2 months, post-injection BCVA measured 20/200 to 20/50 (mean 20/100). At last visit BCVA improved two or more lines in five eyes (83%) and remained the same in one eye (17%). The mean central foveal thickness improved from 263 microm (range, 165 to 393 microm) to 201 microm (range, 126 to 351 microm), representing an average reduction of 62 mum. Only one eye received more than one (2) bevacizumab injections. No significant complications were observed. CONCLUSIONS: In this small series, intravitreal bevacizumab appears to be a safe and effective treatment for SRNV secondary to type 2A IJT. PMID- 17345091 TI - The effects of the phosphodiesterase type V inhibitor sildenafil on human and bovine retinal function in vitro. AB - BACKGROUND: After the ingestion of sildenafil (Viagra), visual adverse events have been reported, possibly caused by an inhibition of the phototransduction cascade by sildenafil via phosphodiesterase (PDE 6). Therefore, we investigated the effects of sildenafil on photoreceptors and postsynaptic neurons of human and bovine retinas using the isolated superfused vertebrate retina technique. METHODS: Human and bovine retina preparations were perfused with an oxygen preequilibrated standard solution. The electroretinogram (ERG) was recorded using Ag/AgCl electrodes. After recording stable ERG amplitudes, sildenafil was added to the solution for 45 min. Thereupon, the preparations were reperfused with standard solution for 240 min. RESULTS: Following the application of sildenafil (3 microMol/l), the b-wave amplitude of bovine and human preparations was reduced continuously and disappeared completely. After reperfusion with the standard solution for 4 h, the b-wave amplitude did not recover completely. Using the same sildenafil concentration (3 microMol/l), the a-wave amplitude of the human retina was not totally abolished, but reduced to 21% of the initial amplitude and remained reduced at washout. For all retinal preparations, the implicit time of the ERG amplitudes remained significantly extended at the end of the washout. CONCLUSIONS: Strong similarities were detected in the drug-induced changes of the ERG when comparing human and bovine retinas. The results suggest that sildenafil impairs retinal function at not only the level of the photoreceptors, but it also affects the neuronal network of the inner retina at concentrations of approximately 30-fold higher than at therapeutic plasma concentrations. PMID- 17345092 TI - Treatment of basal cell carcinoma of the eyelids with 5% topical imiquimod: a 3 year follow-up study. AB - BACKGROUND: The aim of this study was to determine the efficacy and safety of 5% topical imiquimod, and the long-term results following its use, in the treatment of nodular basal cell carcinoma (BCC) of the eyelid. METHODS: Imiquimod cream (5%) was applied topically to five individuals affected by nodular BCC of the eyelid. The patients were followed up during the 6 weeks of treatment and for another 3 years after treatment. Local side effects and evidence of tumour regression or recurrence were noted. RESULTS: Complete clinical clearance of the tumour was obtained in four patients, with no response in the fifth patient. Therapy was typically accompanied by significant discomfort due to local side effects, which disappeared following completion of the treatment. None of these patients showed any local recurrence after 3 years. CONCLUSIONS: Topical imiquimod applied in the form of a 5% cream proved to be a safe, efficacious and sustainable treatment option for nodular BCC of the eyelid in our selected cases. PMID- 17345093 TI - Transmural variations in gene expression of stretch-modulated proteins in the rat left ventricle. AB - The properties of left ventricular cardiac myocytes vary transmurally. This may be related to the gradients of stress and strain experienced in vivo across the ventricular wall. We tested the hypothesis that within the rat left ventricle there are transmural differences in the expression of genes for proteins that are involved in mechanosensitive pathways and in associated physiological responses. Real time reverse transcription polymerase chain reaction was used to measure messenger RNA (mRNA) levels of selected targets in sub-epicardial (EPI) and sub endocardial (ENDO) myocardium. Carbon fibres were attached to single myocytes to stretch them and to record contractility. We observed that the slow positive inotropic response to stretch was not different between EPI and ENDO myocytes and consistent with this, that the mRNA expression of two proteins implicated in the slow response, non-specific cationic mechanosensitive channels (TRPC-1) and Na/H exchanger, were not different. However, mRNA levels of other targets, e.g. the mechanosensitive K(+) channel TREK-1, Brain Natriuretic Peptide and Endothelin-1 receptor B, were significantly greater in ENDO than EPI. No targets had significantly greater mRNA levels in EPI than ENDO. On the basis of these findings, we suggest that the response of the ventricle to stretch will depend upon both the regional differences in stimuli and the relative expression of the mechanosensitive targets and that generally, stretch sensitivity is predicted to be greater in ENDO. PMID- 17345094 TI - Endothelial dysfunction in adult patients with a history of Kawasaki disease. AB - To assess the existence of endothelial dysfunction and the possibility of the early onset of atherosclerosis in the chronic stage of Kawasaki disease (KD), we examined endothelial function in adult patients late after the onset of KD. We evaluated two age-matched groups: 35 adult KD patients (KD group) (mean age, 27.0 years; mean interval time, 24.1 years), and 36 healthy adults (control group). To assess vascular endothelial function, flow-mediated dilatation (%FMD) of the brachial artery and urinary nitrites and nitrates (NOx) were examined. We also measured adhesion molecules and several coagulation-fibrinolysis markers. In addition, we measured high-sensitive C-reactive protein (hs-CRP) as a chronic inflammatory marker, and brachial-ankle pulse wave velocity (baPWV) as a marker for arterial stiffness. %FMD was significantly reduced in the KD group when compared with that of the control group (KD group, 10.4 +/- 2.6%; control group, 14.4 +/- 3.2%, p<0.05), particularly in patients with coronary artery lesions. Thrombin-antithrombin III complex values were higher in the KD group, although no significant differences were observed in the other markers for endothelial function. Hs-CRP was significantly elevated only in the patients with coronary aneurysms. Furthermore, in the male KD patients, the baPWV values were significantly higher than those in the control subjects. This study revealed that the adult patients with a history of KD had systemic vascular endothelial dysfunction, and also suggested that a history of KD was possibly one of the risk factors for early onset of atherosclerosis. PMID- 17345095 TI - Myocardial scintigraphy after pacemaker implantation for congenital complete atrioventricular block. AB - Patients with isolated congenital complete atrioventricular block (CCAVB) occasionally develop dilated cardiomyopathy (DCM), despite early pacemaker implantation. However, the etiology of the DCM and its relationship to permanent ventricular pacing are not fully understood. Twenty-five patients with CCAVB underwent (99m) technetium (Tc) myocardial perfusion scintigraphy. Five patients were studied before and after pacing, providing a total of 30 image sets, which were divided into three groups; group 1: CCAVB before pacemaker implantation (PMI) (n = 11); group 2: CCAVB after PMI who did not subsequently develop DCM (n = 13); group 3: CCAVB after PMI who subsequently developed DCM (n = 6). Perfusion defects on single-photon-emission computed tomography (SPECT) were identified in group 1, 0 of 11 patients; group 2, 85% of patients; and group 3, 100% of patients. In groups 2 and 3, in patients with right ventricular pacing, the perfusion defects were mainly in the septum or between the apex and septum. On 20 segments' polar maps, the distribution of %uptake showed a similar pattern in groups 2 and 3, the degree of decreased %uptake and the number of segments with decreased %uptake being more severe in group 3. "Artificial" left bundle branch block (LBBB) pattern myocardial contraction induced by right ventricular pacing decreased myocardial perfusion around the apex and septum. Some patients with CCAVB will develop left ventricular dysfunction caused by artificial LBBB-induced interventricular asynchrony. PMID- 17345096 TI - Scimitar syndrome: incidence, treatment, and prognosis. AB - This study is based on a database of 16 years; we sought to define the incidence and outcome of scimitar syndrome. Of 8,771 patients, 5 (0.057%) with scimitar syndrome were identified and constituted the study population. Follow-up ranged from 1 to 16 years (median: 10 years). Diagnosis was assured by computed tomography in four patients and by cardiac catheterization in one. Two patients presented with respiratory distress soon after birth and required early pneumonectomy in one case and coil embolization of the abnormal feeding arteries to the right lower lung followed by surgical rerouting of the abnormal pulmonary vein and repair of the atrial septal defect in the other case. The former was supported by ventilator therapy for 3 years after pneumonectomy, but was finally weaned from the ventilator. Among the other three, two had repeated pneumonia that resolved after rerouting of the abnormal right pulmonary vein and cardiac repair. The asymptomatic child did not receive any intervention. In spite of the abnormal orientation of the airways, none of the four patients with detailed computed tomography imaging showed any significant compression of the airways. All five patients were doing well as of the last follow-up. In conclusion, scimitar syndrome is a very rare disease in this Asian country and the varied symptoms, such as tachypnea and repeated infection, could be improved after interventions. PMID- 17345097 TI - Characterization of irritable bowel syndrome and constipation in children with allergic diseases. AB - Allergy is believed to play a role in the pathogenesis of irritable bowel syndrome (IBS) and constipation. We investigated whether allergic patients are more prone to constipation or IBS. In a multicenter study, two groups of outpatient children aged 3-13 years were included. In group 1, children with allergic symptoms were enrolled. Group 2 consisted of nonallergic children. In both groups, the assessment of IBS and constipation was carried out using a questionnaire based on the Rome criteria for functional gastrointestinal disorders. All children were examined and underwent skin prick tests (SPT) to foods and aeroallergens. The allergic group (n=196) and controls (n=127) were comparable with respect to sex, age, and anthropometric parameters. IBS was found in 6.6% of the allergic children and in 6.3% of the controls (p=0.581). The frequency of constipation was similar in the two groups. In allergic children, positive SPTs to food and self-reported reactions to food were associated with IBS. Our results show that evaluation of constipation comorbidity is not required in allergic children. In allergic children with positive SPT to foods attention may be paid to IBS symptoms. PMID- 17345098 TI - Medication use during pregnancy and the risk of childhood cancer in the offspring. AB - The young age at onset of many cancers in childhood has led to investigations on maternal exposures during pregnancy. Data from a population-based case-control study in Germany (1992-1997) that included 1,867 cases and 2,057 controls was used to investigate this question. Maternal use of vitamin, folate or iron supplementation was associated with a reduced risk of non-Hodgkin lymphoma and tumors and, less clearly, with leukemia, but not with CNS tumors. An increased risk of neuroblastoma was associated most markedly with diuretics and other antihypertensives, but also with vitamin, folate or iron supplementation. No associations were seen with pain relievers, antinauseants or cold medications, nor with delivery by Caesarian section. The strengths of this study are its population base, the large number of cases and the inclusion of different case groups to identify disease specificity of associations. The limitation of this study is an exposure assessment relying on maternal self-reports. In conclusion, these data indicate a potential influence of some maternal medication during pregnancy on the risk of childhood cancer in the offspring; however, no clear picture is seen. PMID- 17345099 TI - Distribution of TRPC4 in developing and adult murine brain. AB - The transient receptor potential (TRP) superfamily comprises of a group of non selective cation channels that have been implicated in both receptor and store operated channel functions. The family of classical TRPs (TRPCs) consists of seven members (TRPC1-7), with TRPC4 possibly playing a role in neuronal signaling. We have examined the distribution pattern of TRPC4 mRNA and protein in the developing and postnatal murine brain by using in situ hybridization, Western blotting, and immunocytochemistry. Expression of TRPC4 mRNA starts at embryonic day 14.5 (E14.5) in the developing septal area and cerebellar anlagen. At E16.5, prominent expression is additionally seen in the hippocampal formation and cortical plate. High densities of cells expressing TRPC4 mRNA occur in the adult olfactory bulb and hippocampus, whereas the cortex and septum display lower densities of cells positive for TRPC4 mRNA. Analysis of the adult hippocampal formation has revealed TRPC4 immunoreactivity in hippocampal areas CA1 to CA3 and in the dentate gyrus. Functions consistent with this spatially restricted pattern of expression remain to be revealed. PMID- 17345100 TI - STAT3 and COX-2 activation in the guinea-pig brain during fever induced by the Toll-like receptor-3 agonist polyinosinic:polycytidylic acid. AB - Intra-arterial injections of synthetic double-stranded RNA (polyinosinic:polycytidylic acid, PIPC) at a dose of 500 microg/kg evoked pronounced fever in guinea-pigs. PIPC-induced fever could be antagonized by treatment with the non-selective cyclooxygenase (COX) inhibitor diclofenac and was, in part, attenuated by the administration of the selective COX-2-inhibitor nimesulide (dose: 5 mg/kg for both COX inhibitors). We further investigated whether direct activation of brain cells during PIPC-induced fever could be demonstrated. Using radioactive in situ hybridization, we demonstrated that treatment with PIPC resulted in an upregulation of COX-2 and interleukin-1 beta mRNA in the guinea-pig brain. Thus, COX-2-specific hybridization signals seemed to be mainly associated with brain blood vessels. Intra-arterial injections of PIPC further induced the pronounced nuclear translocation of the transcription factor STAT3 in the endothelium of various fore- and hindbrain areas and in the meninges. In brain structures that lacked a tight blood-brain barrier, i.e. the sensory circumventricular organs (area postrema, vascular organ of laminae terminalis, subfornical organ), the astrocytes and a population of still undetermined cellular phenotype also showed marked STAT3 activation in response to PIPC. The Toll-like receptor-3 agonist PIPC therefore caused a similar activation of brain cells as that reported for other experimental models of systemic inflammation. PMID- 17345101 TI - The allometry of echolocation call frequencies of insectivorous bats: why do some species deviate from the pattern? AB - The peak echolocation frequency of insectivorous bats generally declines as body size increases. However, there are notable exceptions to this rule, with some species, such as Rhinolophus clivosus, having a higher than expected peak frequency for their body size. Such deviations from allometry may be associated with partitioning of foraging habitat (the foraging habitat hypothesis) or insect prey (the prey detection hypothesis). Alternatively, the deviations may be associated with the partitioning of sonar frequency bands to allow effective communication in a social context (the acoustic communication hypothesis). We tested the predictions of these hypotheses through comparisons at the family, clade and species level, using species of rhinolophids in general and R. clivosus, a species with a wide distribution, as a specific test case. We compared the wing parameters, echolocation frequency and ecology of R. clivosus to those of the sympatric R. capensis. Rhinolophus clivosus has a much higher echolocation frequency than predicted from its wing loading or body mass. Furthermore, contrary to the predictions of the foraging habitat hypothesis, we found no difference in foraging habitat between R. clivosus and R. capensis. The size range of insect prey taken by the two species also overlapped almost completely, contrary to the prey detection hypothesis. On the other hand, the variation of echolocation frequencies around the allometric relationship for rhinolophids was smaller than that for Myotis spp., supporting the prediction of the acoustic communication hypothesis. We thus propose that the relatively high peak frequency of R. clivosus is the result of partitioning of sonar frequency bands to minimize the ambiguity of echolocation calls during social interactions. PMID- 17345102 TI - Soil microorganisms control plant ectoparasitic nematodes in natural coastal foredunes. AB - Belowground herbivores can exert important controls on the composition of natural plant communities. Until now, relatively few studies have investigated which factors may control the abundance of belowground herbivores. In Dutch coastal foredunes, the root-feeding nematode Tylenchorhynchus ventralis is capable of reducing the performance of the dominant grass Ammophila arenaria (Marram grass). However, field surveys show that populations of this nematode usually are controlled to nondamaging densities, but the control mechanism is unknown. In the present study, we first established that T. ventralis populations are top-down controlled by soil biota. Then, selective removal of soil fauna suggested that soil microorganisms play an important role in controlling T. ventralis. This result was confirmed by an experiment where selective inoculation of microarthropods, nematodes and microbes together with T. ventralis into sterilized dune soil resulted in nematode control when microbes were present. Adding nematodes had some effect, whereas microarthropods did not have a significant effect on T. ventralis. Our results have important implications for the appreciation of herbivore controls in natural soils. Soil food web models assume that herbivorous nematodes are controlled by predaceous invertebrates, whereas many biological control studies focus on managing nematode abundance by soil microorganisms. We propose that soil microorganisms play a more important role than do carnivorous soil invertebrates in the top-down control of herbivorous ectoparasitic nematodes in natural ecosystems. This is opposite to many studies on factors controlling root-feeding insects, which are supposed to be controlled by carnivorous invertebrates, parasitoids, or entomopathogenic nematodes. Our conclusion is that the ectoparasitic nematode T. ventralis is potentially able to limit productivity of the dune grass A. arenaria but that soil organisms, mostly microorganisms, usually prevent the development of growth reducing population densities. PMID- 17345103 TI - Manipulation of parasitoid size using the temperature-size rule: fitness consequences. AB - The phenotypic effects of rearing temperature on several fitness components of the koinobiont parasitoid, Aphidius colemani, were examined. Temperatures experienced during development induced a plastic linear response in the dry and fat masses of the immature stage and a non-linear response in the growth rate as well as in the size of adults. We investigated if the phenotypic morphometrical plasticity exhibited by parasitoids reared at different temperatures can induce variations in fitness-related traits in females. We did not find any difference in immature (pupal) mortality in accordance to rearing temperature. However, when examining adult longevity, we found an inverse linear relation with developmental temperature, confirming the usual rule that larger and fatter wasps live longer than smaller ones. The pattern of female fecundity was non-linear; wasps that developed at high and low temperatures were less productive. We suggest that when development is short, the accumulated reserves are not adequate to support both fecundity and survival. By manipulating adult size through changes in the rearing temperature, we showed that the usual shape of the size/fitness function is not always linear as expected. Developmental temperature induced a plasticity in energy reserves which affected the functional constraints between survival and reproduction. PMID- 17345104 TI - The disruption of dominance hierarchies by a non-native species: an individual based analysis. AB - We studied the effects of the exotic rainbow trout (Oncorhynchus mykiss) on the performance and the dominance hierarchy of native Atlantic salmon (Salmo salar) at the group and individual level using laboratory and semi-natural experiments. At the group level, we compared the effects of interspecific and intraspecific competition (substitutive and additive design) on behavioural responses and growth of young-of-the-year Atlantic salmon. At the individual level, the same design was used to evaluate: (1) the temporal consistency of behavioural responses, dominance hierarchy and growth rate of Atlantic salmon; (2) the pattern of correlations between behaviours; and (3) the relationship between individual growth rate and behaviour. In the laboratory, group-level analyses revealed a weak but similar effect of rainbow trout and intraspecific competition on the behaviour and growth of Atlantic salmon. In contrast, individual-based analyses demonstrated that rainbow trout (but not intraspecific competition) strongly affected behavioural strategy, dominance hierarchy and growth trajectory of individual Atlantic salmon. Specifically, behaviours, dominance status and growth rate of salmon were temporally consistent in the intraspecific environment, while these patterns were disrupted when rainbow trout were present. Similarly, we found that rainbow trout strongly affected behavioural correlations and the relationships between individual growth rate and behaviour. The semi natural experiments confirmed these results as interspecific competition affected relationships between individual growth rate of salmon, initial weight and activity index. Overall, individual-based analyses highlighted important mechanisms that were concealed at the group level, and that may be crucial to understand ecological and evolutionary consequences of exotic species. Moreover, these results demonstrated that competition with an exotic species disrupts the hierarchical relationship among native individuals and may therefore represent a potential for a shift in selective pressure. PMID- 17345105 TI - Ectomycorrhizal fungi associated with ponderosa pine and Douglas-fir: a comparison of species richness in native western North American forests and Patagonian plantations from Argentina. AB - The putative ectomycorrhizal fungal species registered from sporocarps associated with ponderosa pine and Douglas-fir forests in their natural range distribution (i.e., western Canada, USA, and Mexico) and from plantations in south Argentina and other parts of the world are listed. One hundred and fifty seven taxa are reported for native ponderosa pine forests and 514 taxa for native Douglas-fir forests based on available literature and databases. A small group of genera comprises a high proportion of the species richness for native Douglas-fir (i.e., Cortinarius, Inocybe, and Russula), whereas in native ponderosa pine, the species richness is more evenly distributed among several genera. The comparison between ectomycorrhizal species richness associated with both trees in native forests and in Patagonia (Argentina) shows far fewer species in the latter, with 18 taxa for the ponderosa pine and 15 for the Douglas-fir. Epigeous species richness is clearly dominant in native Douglas-fir, whereas a more balanced relation epigeous/hypogeous richness is observed for native ponderosa pine; a similar trend was observed for Patagonian plantations. Most fungi in Patagonian Douglas fir plantations have not been recorded in plantations elsewhere, except Suillus lakei and Thelephora terrestris, and only 56% of the fungal taxa recorded in Douglas-fir plantations around the world are known from native forests, the other taxa being new associations for this host, suggesting that new tree + ectomycorrhizal fungal taxa associations are favored in artificial situations as plantations. PMID- 17345107 TI - Towards superconductivity in hydrides: computational studies of two hypothetical ternary compounds, Yb(II)BeH4 and Cs3Yb(III)H6. AB - Two examples of novel, as yet unsynthesized ternary lanthanide hydrides- Yb(II)BeH4 and Cs3Yb(III)H6--are investigated computationally. Their unprecedented electronic structure is discussed and the potential superconductivity of Cs3Yb(III)H6 explored. Methods of synthesis are postulated for both compounds. PMID- 17345106 TI - Real-time kinetics of discontinuous and highly conformational metal-ion binding sites of prion protein. AB - The prion protein (PrP) is a metalloprotein with an unstructured region covering residues 60-91 that bind two to six Cu(II) ions cooperatively. Cu can bind to PrP regions C-terminally to the octarepeat region involving residues His111 and/or His96. In addition to Cu(II), PrP binds Zn(II), Mn(II) and Ni(II) with binding constants several orders of magnitudes lower than those determined for Cu. We used for the first time surface plasmon resonance (SPR) analysis to dissect metal binding to specific sites of PrP domains and to determine binding kinetics in real time. A biosensor assay was established to measure the binding of PrP derived synthetic peptides and recombinant PrP to nitrilotriacetic acid chelated divalent metal ions. We have identified two separate binding regions for binding of Cu to PrP by SPR, one in the octarepeat region and the second provided by His96 and His111, of which His96 is more essential for Cu coordination. The octarepeat region at the N-terminus of PrP increases the affinity for Cu of the full-length protein by a factor of 2, indicating a cooperative effect. Since none of the synthetic peptides covering the octarepeat region bound to Mn and recombinant PrP lacking this sequence were able to bind Mn, we propose a conformational binding site for Mn involving residues 91-230. A novel low affinity binding site for Co(II) was discovered between PrP residues 104 and 114, with residue His111 being the key amino acid for coordinating Co(II). His111 is essential for Co(II) binding, whereas His96 is more important than His111 for binding of Cu(II). PMID- 17345108 TI - 3D-QSAR studies of substituted 1-(3, 3-diphenylpropyl)-piperidinyl amides and ureas as CCR5 receptor antagonists. AB - 3D-QSAR studies on the derivatives of 1-(3,3-diphenylpropyl)-piperidinyl amide and urea as CCR5 receptor antagonists were performed by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA) methods to rationalize the structural requirements responsible for the inhibitory activity of these compounds. The global minimum energy conformer of the template molecule, the most active and pharmacokinetically stable molecule of the series, was obtained by systematic search and used to build structures of the molecules in the dataset. The best predictions for the CCR5-receptor were obtained with the CoMFA standard model (q (2) = 0.787, r (2) = 0.962) and CoMSIA model combined steric, electrostatic and hydrophobic fields (q (2) = 0.809, r (2) = 0.951). The predictive ability of CoMFA and CoMSIA were determined using a test set of 12 compounds giving predictive correlation coefficients of 0.855 and 0.83, respectively, indicating good predictive power. Further, the robustness of the model was verified by bootstrapping analysis. The contour maps produced by the CoMFA and CoMSIA models were used to identify the structural features relevant to the biological activity in this series. Based on the CoMFA and CoMSIA analysis, we have identified some key features in the series that are responsible for CCR5 antagonistic activity which may be used to design more potent 1-(3,3 diphenylpropyl)-piperidinyl derivatives and predict their activity prior to synthesis. PMID- 17345109 TI - [Dimensional ridge alterations following tooth extraction. An experimental study in the dog]. AB - The aim of the present study was to histologically evaluate extraction wound healing after socket preservation using a beta-TCP root taper.Ten dogs were used in the study. Immediately following careful extraction of the first premolar of the lower jaw the extraction sockets were filled using a chair-side thermically formed polylactide-linked root taper (RT). To avoid contamination, a further polylactide barrier covered the crestal surface of the taper. Untreated extraction sites of the opposite side served as control. After three and six months of healing, the animals were sacrified and dissected blocks were prepared for histomorphometrical analysis. Following parameters were evaluated: difference between lingual and buccal bone height, lingual and buccal alveolar wall and total bone width 1, 3 and 5mm underneath the top of the respective crest. During the entire study period healing was uneventful for all animals. Histological analysis of three months specimens revealed a definable area of minor mineralized bone within the former extraction sockets in both RT and control group. In the test group small areas of material organized by connective tissue but no remnants of the bone substitute material could be observed. After six months the borderline between new and pre-existing bone had disappeared. Histomorphometric analysis revealed no statistically significant differences between test and control group after three or six months (p>0.05, paired T-test). Within the limits of the present study it was concluded that the application of polylactide stabilized RT does not improve the dimensional ridge alterations after tooth extraction. PMID- 17345110 TI - [The impact of radiotherapy on quality of life -- a survey of 1411 patients with oral cancer]. AB - PURPOSE: The therapy of patients with oral cancer often requires a combination of surgery and radiotherapy. This leads to trauma of healthy tissue. The impact of this side effect on quality of life was investigated. Additionally the impairment of 19 factors was determined (comprehension of speech for unknown others, comprehension of speech for familiar others, eating/swallowing, mobility of the tongue, opening range of the mouth, mobility of lower jaw, mobility of neck, mobility of arms and shoulders, sense of taste, sense of smell, appearance, strength, appetite, respiration, pain, swelling, xerostomia, halitosis). METHODS: This retrospective multicenter study was conducted under the auspices of DOESAK (a German, Austrian and Swiss cooperative group on tumors of the maxillofacial region). The Bochum Questionnaire on Rehabilitation was used to determine 147 items. 3894 questionnaires where sent to 43 clinics in Germany, Austria and Switzerland. 1761 questionnaires where returned, while 1411 of them included all of the answers necessary for this study. RESULTS: 686 of 1411 patients where irradiated. Before the beginning of therapy the impairment of the 19 factors was not significantly higher in the group that later received radiotherapy. After therapy there is a significantly higher impairment of the irradiated patients. The factors that are especially worse are xerostomia, swallowing and understanding of speech. The quality of life was not significantly lower. CONCLUSIONS: Although radiotherapy leads to trauma of healthy tissue this method is indicated as it has no significant impact on quality of life. During the rehabilitation physiotherapists should relieve the impairment of speech, eating and swallowing. PMID- 17345111 TI - [History and use of fillers for treating wrinkles]. AB - The development of injectable fillers for filling in depressions or wrinkles in the face is reviewed. After the hesitant interest on fillers to correct scars and depressions which started at the end of the 19th century, the development of new substances continued at a dizzying pace when public demand to treat the signs of aging increased dramatically starting in the mid 1980s. This led to a countless number of different substances. To obtain an optimal result in treating facial wrinkles or depressions the appropriate filler must be injected with a technique that suits best the individual indication. Fillers are classified in resorbable and non-resorbable permanent fillers. With resorbable fillers only a temporary result can be obtained, which means that the patient has to undergo repetitive treatments. With permanent, non-resorbable fillers long lasting results can be obtained that may last for years and even decades. All fillers may have side effects like swelling, erythema, nodules right after treatment and in very rare cases years after the injection foreign body granulomas may develop that may be resistant to treatment. PMID- 17345112 TI - Rebleeding of ruptured cerebral aneurysms during three-dimensional computed tomographic angiography: report of two cases and literature review. AB - Although three-dimensional computed tomographic angiography (3D-CTA) is less complicated and time-consuming than conventional cerebral angiography (CCA) and represents a reliable alternative for evaluating cerebral aneurysms, some patients experience aneurysmal rerupture during 3D-CTA. Two women, 79 and 71 years old, who presented with severe subarachnoid hemorrhage (SAH) underwent 3D CTA within 3 h after SAH onset. Their images clearly indicated extravasation from their aneurysms. Neither patient recovered from deep coma, and both died within 2 days. We reviewed the literature with special reference to the condition of SAH patients at admission and the interval between SAH onset and 3D-CTA, and discuss serious complications of 3D-CTA study. Although aneurysmal rerupture may reflect the natural course, rerupture during 3D-CTA, especially in SAH patients who are in poor clinical condition during the acute stage, should be recognized as a potentially fatal complication. Their blood pressure must be strictly controlled and factors such as their clinical condition and the interval from the ictus must be considered. PMID- 17345113 TI - Effects of magnesium sulfate on dynamic changes of brain glucose and its metabolites during a short-term forced swimming in gerbils. AB - This investigation examined the acute effects of magnesium on the dynamic changes of brain glucose, lactate, pyruvate and magnesium levels in conscious gerbils during forced swimming. Gerbils were pretreated with saline (control group) and magnesium sulfate (90 mg kg(-1), intraperitoneal injection) before a 15 min forced swimming period. The basal levels of glucose, pyruvate, lactate, and magnesium in brain dialysates were 338 +/- 18, 21 +/- 2, 450 +/- 39, and 2.1 +/- 0.1 microM, respectively, with no significant difference between groups. Magnesium levels were found slightly higher (but not significant) in the magnesium-treated group. However, brain glucose and pyruvate levels in the control group decreased to about 50 and 60% of the basal level (P = 0.01) after swimming, respectively. Pretreatment with magnesium sulfate immediately increased glucose levels to about 140% of the basal level, and increased pyruvate levels to about 150% of the basal level during forced swimming (P = 0.01). Both glucose and pyruvate levels returned to the basal level after 30 min of the recovery. The lactate levels of the control group increased to about 160% of the basal level (P = 0.01) during swimming, whereas pretreatment with magnesium sulfate attenuated lactate levels to 130% of the basal level (P = 0.01). Magnesium supplementation may be beneficial because it provides an additional glucose source and may also promote the recovery of energy substrates in the brain during and after forced exercise. In order to achieve optimal physical performance, further investigation as to dosage of magnesium supplementation is needed. PMID- 17345114 TI - Full-length sequence analysis of the HLA-DRB1 locus suggests a recent origin of alleles. AB - The HLA region harbors some of the most polymorphic loci in the human genome. Among them is the class II locus HLA-DRB1, with more than 400 known alleles. The age of the polymorphism and the rate at which new alleles are generated at HLA loci has caused much controversy over the years. Previous studies have mostly been restricted to the 270 base pairs that constitute the second exon and represent the most variable part of the gene. Here, we investigate the evolutionary history of the HLA-DRB1 locus on the basis of an analysis of 15 genomic full-length alleles (10-15 kb). In addition, the variation in 49 complete coding sequences and 322 exon 2 sequences were analyzed. When excluding exon 2 from the analysis, the diversity at the synonymous sites was found to be similar to the intron diversity. The overall diversity in noncoding region was also similar to the genome average. The DRB1*03 lineage has been found in human, chimpanzee, bonobo, gorilla, and orangutan. An ancestral "proto HLA-DRB1*03 lineage" appeared to have diverged in the last 5 million years into the human specific lineages *08, *11, *13, and *14. With exception to exon 2, both the coding- and the noncoding diversity suggests a recent origin (<1 million years ago) for most of the alleles at the HLA-DRB1 locus. Sites encoding for amino acids involved in antigen binding [antigen recognizing sites (ARS)] appear to have a more ancient origin. Taken together, the recent origin of most alleles, the high diversity between allelic lineages, and the ancient origin of sequence motifs in exon 2, is consistent with a relatively rapid generation of novel alleles by gene conversion like events. PMID- 17345115 TI - Two variable lymphocyte receptor genes of the inshore hagfish are located far apart on the same chromosome. AB - Variable lymphocyte receptors (VLR) generate enormous diversity through assembling highly diverse leucine-rich repeat (LRR) modules and presumably function as antigen receptors in jawless vertebrates. The hagfish, which constitute major extant members of jawless vertebrates along with lampreys, have two VLR genes designated VLRA and VLRB, whereas only a single VLR gene has been identified in the lamprey. In the present study, we show by fluorescence in situ hybridization (FISH) that hagfish VLRA and VLRB are located on the same chromosome, but are far apart from each other. Analysis of available inshore hagfish complementary DNA sequences indicates that VLRA and VLRB do not share a LRR module with an identical nucleotide sequence. Physical separation of VLRA and VLRB is consistent with this observation and indicates that the two VLR genes function as separate units. The FISH protocol developed in this study should be useful for the analysis of the agnathan genome. PMID- 17345116 TI - Purification and characterization of an alkaline protease from the marine yeast Aureobasidium pullulans for bioactive peptide production from different sources. AB - The extracellular alkaline protease in the supernatant of cell culture of the marine yeast Aureobasidium pullulans 10 was purified to homogeneity with a 2.1 fold increase in specific protease activity as compared to that in the supernatant by ammonium sulfate fractionation, gel filtration chromatography (Sephadex G-75), and anion-exchange chromatography (DEAE Sepharose Fast Flow). According to the sodium dodecyl sulfate-polyacrylamide gel electrophoresis data, the molecular mass of the purified enzyme was estimated to be 32.0 kDa. The optimal pH and temperature of the purified enzyme were 9.0 and 45 degrees C, respectively. The enzyme was activated by Cu(2+) (at a concentration of 1.0 mM) and Mn(2+) and inhibited by Hg(2+), Fe(2+), Fe(3+), Zn(2+), and Co(2+). The enzyme was strongly inhibited by phenylmethylsulfonyl fluoride, but weakly inhibited by EDTA, 1-10-phenanthroline, and iodoacetic acid. The K(m) and V(max) values of the purified enzyme for casein were 0.25 mg/ml and 0.0286 micromol/min/mg of protein, respectively. After digestion of shrimp protein, spirulina (Arthospira platensis) protein, proteins of marine yeast strains N3C (Yarrowia lipolytica) and YA03a (Hanseniaspora uvarum), milk protein, and casein with the purified alkaline protease, angiotensin I converting enzyme (ACE) inhibitory activities of the resulting peptides reached 85.3%, 12.1%, 29.8%, 22.8%, 14.1%, and 15.5%, respectively, while the antioxidant activities of these were 52.1%. 54.6%, 25.1%, 35%, 12.5%, and 24.2%, respectively, indicating that ACE inhibitory activity of the resulting peptides from the shrimp protein and antioxidant activity of those produced from the spirulina protein were the highest, respectively. These results suggest that the bioactive peptides produced by digestion of the shrimp protein with the purified alkaline protease have potential applications in the food and pharmaceutical industries. PMID- 17345117 TI - Surgical outcome of elderly patients 75 years of age and older with thoracic esophageal carcinoma. AB - BACKGROUND: This study aimed to evaluate the surgical outcome of esophagectomy in patients 75 years of age and older with thoracic esophageal carcinoma. PATIENTS AND METHODS: Between 1980 and 2002, 55 (46%) of 120 patients 75 years of age and older with thoracic esophageal carcinoma underwent an esophagectomy. The risk factors that resulted in decreased survival were analyzed by both univariate and multivariate analyses. Differences in surgical outcome and long-term survival between the earlier time period (1980-1989) and later time period (1990-2002) were analyzed separately. RESULTS: Overall resection rate in elderly patients in both periods was similar (44%, earlier period; 46%, later period). Postoperative complications significantly reduced long-term survival [adjusted hazard ratio for death, 4.05; 95% confidence interval (CI), 1.70-9.62; P < 0.01). Surgical blood loss greater than 1,000 ml was less frequently observed in the later period than in the earlier period (19% vs. 54%, P = 0.01). The postoperative morbidity rate was lower in the later than in the earlier period (29% vs. 63%, P = 0.02). Overall 5-year survival rate was significantly higher in the later period than in the earlier period (57% vs. 18%, P < 0.01). CONCLUSIONS: Elderly patients who underwent an esophagectomy in the later period appeared to manifest less neoadjuvant treatment, less surgical stress, fewer postoperative complications, and a better long-term survival than those treated in the earlier period. PMID- 17345118 TI - Crossing boundaries. PMID- 17345120 TI - Special variants of differentiated thyroid cancer: does it alter the extent of surgery versus well-differentiated thyroid cancer? AB - INTRODUCTION: Recently, more aggressive variants of so-called well-differentiated thyroid carcinomas have been identified such as the tall cell variant, columnar cell variant, diffuse sclerosing variant, insular carcinoma, and Hurthle cell (oncocytic, oxyphilic) carcinomas. METHODS: An evidence-based review was performed to identify the optimal treatment recommendations for these thyroid cancers of intermediate differentiation. CONCLUSIONS: Although some variation exists within the group, aggressive surgical and medical management are recommended for these neoplasias. Any such recommendations should, however, be viewed in the light of the fact that the current literature mainly consists of case reports, case series, and limited reviews. The clinical presentation, pathophysiology, diagnosis, and surgical and medical management for these thyroid cancers with intermediate differentiation are discussed. PMID- 17345121 TI - Comparison of AngioJet rheolytic pharmacomechanical thrombectomy versus AngioJet rheolytic thrombectomy in a porcine peripheral arterial model. AB - INTRODUCTION: Rheolytic thrombectomy using the AngioJet catheter for arterial thrombosis has been shown to be effective in restoring blood flow. Additional infusion of thrombolytic agents via the AngioJet catheter results in combined rheolytic pharmacomechanical thrombolysis (PMT), which further enhances thrombectomy efficacy. However, the histologic response to rheolytic PMT therapy remains unclear. This study compares the acute and chronic vessel wall response and hemolysis due to conventional AngioJet rheolytic thrombectomy (RT) and AngioJet PMT in the porcine peripheral arterial model. METHODS: A total of 19 juvenile pigs were divided into acute and chronic groups. In the acute group (n = 6), bilateral common carotid, femoral, and iliac arteries ranging from 3 to 6 mm in diameter were randomized to the control RT group or to PMT therapy. Vessels were analyzed 4 days following interventions. In the chronic group (n = 5), bilateral common carotid, femoral, and iliac arteries ranging from 3 to 6 mm in diameter were randomized to the control RT group or to PMT therapy. Vessels were analyzed at 30 days following interventions. Hemolytic evaluation was performed in additional eight pigs, which were randomized to either RT or PMT intervention. RESULTS: In the acute group, similar histologic injury grades were noted between the RT- and PMT-treated femoral and iliac vessels. Endothelial denudation in the RT and PMT vessels were 43% and 39% (NS), respectively. Vessels with intact internal elastic lamina (IEL) in the RT and PMT groups were 54% and 57% (NS), respectively. In vessels < 4 mm in diameter, fractured IEL in the AT and PMT groups occurred in 23% and 27% (NS), respectively. The degrees of smooth muscle cell (SMC) loss were similar for the RT- and PMT-treated vessels (45% and 40%, respectively; NS). In the chronic group, no differences were seen between the RT and PMT groups with respect to endothelial denudation, IEL fracture rate, or SMC loss. Similar degrees of medial thickening or intimal hyperplasia were noted in the RT and PMT groups (49% and 43%, respectively; NS). No difference in hemolytic effect was noted in the treatment groups. CONCLUSIONS: AngioJet rheolytic pharmacomechanical thrombectomy treatment incurs an equivalent safety profile in medium-caliber peripheral arteries when compared to rheolytic thrombectomy treatment. No difference in hemolytic reaction occurred in either group. The observed clinical efficacy of rheolytic pharmacomechanical thrombectomy does not result in untoward vessel injury compared to conventional rheolytic thrombectomy therapy. PMID- 17345122 TI - Peripheral arterial occlusive disease: magnetic resonance imaging and the role of aggressive medical management. AB - Atherosclerosis accounts for most peripheral arterial occlusive disease (PAD). Although many of the risk factors for atherosclerotic coronary artery disease (CAD) such as hyperlipidemia have been identified as risk factors for peripheral arterial disease, strong evidence is lacking that risk factor modification is effective in halting progression or improving outcomes. A better understanding is needed regarding the clinical and pathophysiologic responses to risk factor modification. This review describes current advances in the medical management for PAD including lipid modification antiplatelet therapy, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, exercise, and endovascular intervention. In addition, we discuss our active ELIMIT Trial (Effect of Lipid Modification on Peripheral Arterial Disease after Endovascular Intervention). We test the hypothesis that an aggressive regimen of serum lipid modification will inhibit the progression of atherosclerosis in femoral arteries and reduce the incidence of restenosis of femoral arteries following endovascular stenting by decreasing thrombosis and inflammation. This study will provide a novel strategy for retarding or preventing progression of atherosclerosis and re-stenosis of peripheral arterial disease following arterial revascularization procedures. Importantly, our magnetic resonance imaging studies will provide quantitative data on the vascular lesions in PAD. These studies will advance our understanding of the molecular mechanisms of inflammation and thrombosis associated with aggressive lipid modification. PMID- 17345123 TI - Development of small-diameter vascular grafts. AB - INTRODUCTION: Cardiovascular disease, including coronary artery and peripheral vascular pathologies, is the leading cause of mortality in the United States and Western countries. There is a pressing need to develop small-diameter vascular vessels for bypass surgery and other vascular reconstructive procedures. Tissue engineering offers the prospect of being able to meet the demand for replacement of diseased vessels. Significant advances have been made in recent studies and provide confidence that success is attainable. For instance, a completely cellular approach culturing cells into tissue sheets and wrapping these layers was able to form a layered cellular vascular graft with impressive strength. METHODS/RESULTS: In our experiments, decellularization and heparin immobilization grafts from porcine tissues implanted in a canine model could be repopulated from the host cells, indicating the grafts' potential to develop into living tissues that can adapt and respond to changes in the body. CONCLUSIONS: This review summarizes the current status of vascular grafts used clinically, updates the most recent developments on vascular tissue engineering, and discusses the challenges for the future. PMID- 17345124 TI - Giant retroperitoneal sarcomas: a single institution experience. AB - BACKGROUND: Retroperitoneal sarcomas (RS) are a rare group of malignant soft tissue tumors; due to the flexibility of the retroperitoneum, they generally grow to a large size before becoming symptomatic, often involving surrounding structures. Therefore, the surgeon is frequently compelled to perform large excisions. The aim of this study is to assess clinical and pathological factors affecting prognosis in patients with RS who underwent surgical treatment, comparing giant forms (size > or = 25 cm) with smaller ones (size < 25 cm). METHODS: The hospital records of 73 consecutive patients who underwent surgical exploration for primary RS at our unit between 1984 and 2003 were reviewed. Statistical analysis of factors influencing overall and disease-free survival was performed including both the whole group of patients and only those who underwent complete surgical resection. RESULTS: Giant RS showed a lower resectability rate than smaller forms (54.2% vs. 84.2%, P = 0.005). In the group with complete surgical excision (51 out of 73), patients with giant RS had a higher rate of adjacent organ resection compared with the smaller ones (84.2% vs. 53.1%, P = 0.023). Tumor size did not influence prognosis: after complete resection, 5-year overall survival was 60.9% and 56.3% for giant RS and smaller forms respectively, while 5-year disease-free survival was 54.3% and 48.3% for the two groups respectively. Advanced stage, incomplete gross surgical resection, higher tumor grade, non-liposarcoma histology and microscopic infiltration of margins were found to be significantly negative prognostic factors. CONCLUSIONS: The present study confirms the importance of aggressive surgical management for RS, in order to offer these patients the best chance of long-term survival. PMID- 17345125 TI - Outcomes of hepatic resection for a single large hepatocellular carcinoma. AB - BACKGROUND: The proper role of surgical resection, given the various treatment modalities available, needs to be further clarified in patients with a single large hepatocellular carcinoma (HCC). To evaluate the role of surgical resection in this group of patients, we studied the long-term outcomes of patients that received hepatic resection for a single large (> 5-10 cm in diameter) HCC. METHODS: The clinicopathologic data and long-term outcomes of 61 patients with a single large HCC (> 5-10 cm in diameter; L group) were compared with those of 169 patients with a single small HCC (< or = 5 cm; S group). Prognostic factors were evaluated by univariate and multivariate analysis. RESULTS: Operative mortality rates were low in both groups (0.6% in group S and 1.6% in group L), and the incidence of postoperative hepatic failure was rare even in group L (1.6%). The cumulative 5-year overall survival rate in group S was 59.0%, whereas in group L it was 52.9% (p = 0.385), and the corresponding cumulative 5-year disease-free survival rates were 44.1% and 31.7%, respectively (p = 0.063). Child class B was found to predict poor overall and disease-free survival by multivariate analysis versus Child class A in both groups. The presence of microvascular invasion was also identified as a significant prognostic factor, but it only affected disease free survival in the two groups. CONCLUSIONS: Single large HCCs do not require a large extent of hepatic resection and the associated increased risk of postoperative liver failure. The long-term survival of patients with a single large HCC is as good as that of patients with a single small HCC. We conclude that hepatic resection is a safe and effective therapy for single large HCCs. PMID- 17345126 TI - Transient bloodletting of the short gastric vein in the reconstructed gastric tube improves gastric microcirculation during esophagectomy. AB - BACKGROUND: The reasons for anastomotic leakage in esophago-gastrostomy have been proposed to be poor arterial inflow and insufficient venous drainage at the anastomotic site. In order to improve the congestive status, we developed a novel and easy surgical procedure of transient bloodletting from the short gastric vein after making a gastric tube during esophagectomy, and evaluated tissue blood flow. METHODS: Patients with esophageal cancer, who had received transthoracic esophagectomy and gastric tube reconstruction with intrathoracic anastomosis, were enrolled. After making a slender gastric tube, transient bloodletting from the short gastric vein at the most cardiac site was performed for 30 minutes. The tissue blood flow of the proximal end of the gastric tube was measured using a laser Doppler flowmeter, and was compared in the bloodletting group (n = 68) and the control group without bloodletting (n = 8). RESULTS: In the bloodletting group, tissue blood flow 5 minutes after the start of bloodletting was markedly increased in comparison to that before bloodletting (9.5 +/- 4.9 ml/min/100 g vs. 24.1 +/- 5.9 ml/min/100 g). The elevated levels of tissue blood flow remained at almost constant levels after ceasing bloodletting and lasted until esophago gastrostomy (20.1 +/- 3.9 ml/min/100 g). On the contrary, in the control group without bloodletting, tissue blood flows were marginally increased following construction of a gastric tube, but the changes did not reach significant levels. When the tissue blood flow just before esophago-gastrostomy was compared in the bloodletting and control groups, the flows in the bloodletting group were significantly more elevated than those in the control group (20.1 +/- 3.9 vs. 15.2 +/- 4.9 ml/min/100 g). CONCLUSIONS: Transient bloodletting of the short gastric vein in the gastric tube during esophagectomy may improve the microcirculation of the oral side of the gastric tube. PMID- 17345127 TI - Grayanotoxin poisoning from flower of Rhododendron mucronulatum in humans. PMID- 17345128 TI - Inulinase-producing marine yeasts: evaluation of their diversity and inulin hydrolysis by their crude enzymes. AB - Total 427 yeast strains from seawater, sediments, mud of salterns, guts of the marine fish, and marine algae were obtained. After inulinase activity of the yeast cultures was estimated, we found that four strains (OUC1, G7a, OUC2, and G7a1) of the marine yeasts grown in the medium with inulin could secrete a large amount of inulinase into the medium. The results of routine identification and molecular methods show that they belong to Pichia guilliermondii OUC1, Cryptococcus aureus G7a, Yarrowia lipolytica OUC2, and Debaryomyces hansenii G7a1, respectively. The optimal pHs of inulinase activity produced by them were 6.0, 5.0, 5.0, and 5.0, respectively, while the optimal temperatures of inulinase activity produced by them were 60 degrees , 50 degrees , 60 degrees , and 50 degrees C, respectively. A large amount of monosaccharides and a trace amount of oligosaccharides were detected after the hydrolysis by the crude inulinase produced by P. guilliermondii OUC1, indicating that the crude inulinase had a high exoinulinase activity while a large amount of monosaccharides and oligosaccharides were detected after inulin hydrolysis by the crude inulinase produced both by C. aureus G7a and D. hansenii G7a1. However, no monosaccharides and disaccharides were detected after inulin hydrolysis by the crude inulinase produced by Y. lipolytica OUC2, suggesting that the crude inulinase had no exoinulinase activity. PMID- 17345129 TI - Spatial and temporal distribution of the vibrionaceae in coastal waters of Hawaii, Australia, and France. AB - Relatively little is known about large-scale spatial and temporal fluctuations in bacterioplankton, especially within the bacterial families. In general, however, a number of abiotic factors (namely, nutrients and temperature) appear to influence distribution. Community dynamics within the Vibrionaceae are of particular interest to biologists because this family contains a number of important pathogenic, commensal, and mutualist species. Of special interest to this study is the mutualism between sepiolid squids and Vibrio fischeri and Vibrio logei, where host squids seed surrounding waters daily with their bacterial partners. This study seeks to examine the spatial and temporal distribution of the Vibrionaceae with respect to V. fischeri and V. logei in Hawaii, southeastern Australia, and southern France sampling sites. In particular, we examine how the presence of sepiolid squid hosts influences community population structure within the Vibrionaceae. We found that abiotic (temperature) and biotic (host distribution) factors both influence population dynamics. In Hawaii, three sites within squid host habitat contained communities of Vibrionaceae with higher proportions of V. fischeri. In Australia, V. fischeri numbers at host collection sites were greater than other populations; however, there were no spatial or temporal patterns seen at other sample sites. In France, host presence did not appear to influence Vibrio communities, although sampled populations were significantly greater in the winter than summer sampling periods. Results of this study demonstrate the importance of understanding how both abiotic and biotic factors interact to influence bacterial community structure within the Vibrionaceae. PMID- 17345130 TI - Trichoderma harzianum Rifai 1295-22 mediates growth promotion of crack willow (Salix fragilis) saplings in both clean and metal-contaminated soil. AB - We investigated if the plant growth promoting fungus Trichoderma harzianum Rifai 1295-22 (also known as "T22") could be used to enhance the establishment and growth of crack willow (Salix fragilis) in a soil containing no organic or metal pollutants and in a metal-contaminated soil by comparing this fungus with noninoculated controls and an ectomycorrhizal formulation commercially used to enhance the establishment of tree saplings. Crack willow saplings were grown in a temperature-controlled growth room over a period of 5 weeks' in a garden center topsoil and over 12 weeks in a soil which had been used for disposal of building materials and sewage sludge containing elevated levels of heavy metals including cadmium (30 mg kg(-1)), lead (350 mg kg(-1)), manganese (210 mg kg(-1)), nickel (210 mg kg(-1)), and zinc (1,100 mg kg(-1)). After 5 weeks' growth in clean soil, saplings grown with T. harzianum T22 produced shoots and roots that were 40% longer than those of the controls and shoots that were 20% longer than those of saplings grown with ectomycorrhiza (ECM). T. harzianum T22 saplings produced more than double the dry biomass of controls and more than 50% extra biomass than the ECM-treated saplings. After 12 weeks' growth, saplings grown with T. harzianum T22 in the metal-contaminated soil produced 39% more dry weight biomass and were 16% taller than the noninoculated controls. This is the first report of tree growth stimulation by application of Trichoderma to roots, and is especially important as willow is a major source of wood fuel in the quest for renewable energy. These results also suggest willow trees inoculated with T. harzianum T22 could be used to increase the rate of revegetation and phytostabilization of metal-contaminated sites, a property of the fungus never previously demonstrated. PMID- 17345131 TI - Genetic variation among Penicillium crustosum isolates from arctic and other ecological niches. AB - Penicillium crustosum is an important and panglobal contaminant of lipid- and protein-rich foods and feeds. Although it is infrequent in extremely cold environments, we isolated a high number of P. crustosum strains from Arctic coastal, but particularly, subglacial environments in Svalbard, Norway. P. crustosum is extremely consistent in its phenotypic properties, including morphology, physiology, and secondary metabolite production. However, some Arctic isolates differed from other Arctic and non-Arctic strains in their weak growth on creatine and in the production of the secondary metabolite andrastin A. In this study, we characterized genetic variability of P. crustosum strains originating from different Arctic and non-Arctic environments using amplified fragment length polymorphism (AFLP) and, in addition, M13 minisatellite fingerprinting and partial beta-tubulin gene sequencing. Most of the Arctic strains (85%) showed a relatively low variability and polymorphism level. They produced nine different AFLP genotypes grouped into two clusters in accordance with glacier origin and creatine utilization. The rest of the Arctic isolates and isolates from various non-Arctic environments displayed a much greater degree of genetic variability. It seems that in stressful glacial environment low microbial genetic variation is represented by only a few adapted genotypes that were not recovered from nonpolar environments. PMID- 17345132 TI - Finding the needles in the metagenome haystack. AB - In the collective genomes (the metagenome) of the microorganisms inhabiting the Earth's diverse environments is written the history of life on this planet. New molecular tools developed and used for the past 15 years by microbial ecologists are facilitating the extraction, cloning, screening, and sequencing of these genomes. This approach allows microbial ecologists to access and study the full range of microbial diversity, regardless of our ability to culture organisms, and provides an unprecedented access to the breadth of natural products that these genomes encode. However, there is no way that the mere collection of sequences, no matter how expansive, can provide full coverage of the complex world of microbial metagenomes within the foreseeable future. Furthermore, although it is possible to fish out highly informative and useful genes from the sea of gene diversity in the environment, this can be a highly tedious and inefficient procedure. Microbial ecologists must be clever in their pursuit of ecologically relevant, valuable, and niche-defining genomic information within the vast haystack of microbial diversity. In this report, we seek to describe advances and prospects that will help microbial ecologists glean more knowledge from investigations into metagenomes. These include technological advances in sequencing and cloning methodologies, as well as improvements in annotation and comparative sequence analysis. More significant, however, will be ways to focus in on various subsets of the metagenome that may be of particular relevance, either by limiting the target community under study or improving the focus or speed of screening procedures. Lastly, given the cost and infrastructure necessary for large metagenome projects, and the almost inexhaustible amount of data they can produce, trends toward broader use of metagenome data across the research community coupled with the needed investment in bioinformatics infrastructure devoted to metagenomics will no doubt further increase the value of metagenomic studies in various environments. PMID- 17345133 TI - Genotypic microbial community profiling: a critical technical review. AB - Microbial ecology has undergone a profound change in the last two decades with regard to methods employed for the analysis of natural communities. Emphasis has shifted from culturing to the analysis of signature molecules including molecular DNA-based approaches that rely either on direct cloning and sequencing of DNA fragments (shotgun cloning) or often rely on prior amplification of target sequences by use of the polymerase chain reaction (PCR). The pool of PCR products can again be either cloned and sequenced or can be subjected to an increasing variety of genetic profiling methods, including amplified ribosomal DNA restriction analysis, automated ribosomal intergenic spacer analysis, terminal restriction fragment length polymorphism, denaturing gradient gel electrophoresis, temperature gradient gel electrophoresis, single strand conformation polymorphism, and denaturing high-performance liquid chromatography. In this document, we present and critically compare these methods commonly used for the study of microbial diversity. PMID- 17345134 TI - Molecular characterization of sheep ruminal enrichments that detoxify pyrrolizidine alkaloids by denaturing gradient gel electrophoresis and cloning. AB - An enrichment of strictly anaerobic bacteria from ovine rumen fluid, which has previously been named L4M2, is known to detoxify animal hepatotoxins from the pyrrolizidine alkaloid family. These toxins are present in the tansy ragwort plant (Senecio jacobaea). These plants have been described in livestock animals' range forages in regions of the world such as the Northwest United States and South Africa. The bacterial enrichment was characterized by molecular cloning techniques and by the molecular fingerprinting technique of denaturing gradient gel electrophoresis (DGGE). Phylogenetic analysis of the enrichment revealed that the consortium is composed of no more than five putative bacterial species which associated to the Anaerovibrio, Desulfovibrio, Megasphaera, Prevotella, and Synergistes generas. These are all known to exist in the upper gastrointestinal tract of ruminant animals. This work improved upon previous attempts to characterize the consortium by obtaining nearly full-length ribosomal 16S rDNA sequences through cloning. The DGGE results were directly compared to the cloning data by polymerase chain reaction (PCR) amplifying eight phylogenetically representative clones and analyzing them by DGGE. Direct DGGE analysis of the enrichment displayed greater 16S diversity than the clone library used in this study, suggesting that at least one of the organisms present in the enrichment comprises less than 1% of the total cell population. These data will be used to further refine the enrichment in hopes of future use as a probiotic, which could be administered to animals challenged by the presence of tansy ragwort in their forage. PMID- 17345135 TI - Unravelling microbial communities with DNA-microarrays: challenges and future directions. AB - High-throughput technologies are urgently needed for monitoring the formidable biodiversity and functional capabilities of microorganisms in the environment. Ten years ago, DNA microarrays, miniaturized platforms for highly parallel hybridization reactions, found their way into environmental microbiology and raised great expectations among researchers in the field. In this article, we briefly summarize the state-of-the-art of microarray approaches in microbial ecology research and discuss in more detail crucial problems and promising solutions. Finally, we outline scenarios for an innovative combination of microarrays with other molecular tools for structure-function analysis of complex microbial communities. PMID- 17345136 TI - Molecular evidence for polyphyletic origin of the primary symbionts of sucking lice (phthiraptera, anoplura). AB - Based on 16S rDNA analyses, the primary symbionts of sucking lice were found to form a polyphyletic assemblage of several distant lineages that have arisen several times within Enterobacteriaceae and at least once within Legionellaceae. Another independent lineage of endosymbiotic enterobacteria inhabits a sister group of the sucking lice, Rhynchophthirina. The inspection of 16S rDNA supports the symbiotic nature of the investigated bacteria; they display a typical trait of degenerative processes, an increased AT content (Adenine-Thymine content) in comparison with free-living bacteria. The calculation of divergence time between the closest anopluran and rhynchophthirine symbionts further support their independent origin. The results shown here, together with evidence from other groups, indicate that the significance of primary symbionts for blood-feeding insects should be reconsidered. PMID- 17345137 TI - Effects of experimental lead pollution on the microbial communities associated with Sphagnum fallax (Bryophyta). AB - Ecotoxicological studies usually focus on single microbial species under controlled conditions. As a result, little is known about the responses of different microbial functional groups or individual species to stresses. In an aim to assess the response of complex microbial communities to pollution in their natural habitat, we studied the effect of a simulated lead pollution on the microbial community (bacteria, cyanobacteria, protists, fungi, and micrometazoa) living on Sphagnum fallax. Mosses were grown in the laboratory with 0 (control), 625, and 2,500 microg L(-1) of Pb(2+) diluted in a standard nutrient solution and were sampled after 0, 6, 12, and 20 weeks. The biomasses of bacteria, microalgae, testate amoebae, and ciliates were dramatically and significantly decreased in both Pb addition treatments after 6, 12, and 20 weeks in comparison with the control. The biomass of cyanobacteria declined after 6 and 12 weeks in the highest Pb treatment. The biomasses of fungi, rotifers, and nematodes decreased along the duration of the experiment but were not significantly affected by lead addition. Consequently, the total microbial biomass was lower for both Pb addition treatments after 12 and 20 weeks than in the controls. The community structure was strongly modified due to changes in the densities of testate amoebae and ciliates, whereas the relative contribution of bacteria to the microbial biomass was stable. Differences in responses among the microbial groups suggest changes in the trophic links among them. The correlation between the biomass of bacteria and that of ciliates or testate amoebae increased with increasing Pb loading. We interpret this result as an effect on the grazing pathways of these predators and by the Pb effect on other potential prey (i.e., smaller protists). The community approach used here complements classical ecotoxicological studies by providing clues to the complex effect of pollutant affecting organisms both directly and indirectly through trophic effects and could potentially find applications for pollution monitoring. PMID- 17345138 TI - Pseudomonas fluorescens SBW25 biofilm and planktonic cells have differentiable Raman spectral profiles. AB - Biofilms, and other bacterial aggregations, are of significance in both environmental microbiology and in plant and human pathogenesis. Comparative single-cell Raman spectral analysis can differentiate between planktonic bacteria and those recovered from biofilms and appears to offer a new means by which to investigate bacterial cell physiology, metabolic status, and stress under different environmental conditions. PMID- 17345139 TI - Diel and seasonal variations in abundance, activity, and community structure of particle-attached and free-living bacteria in NW Mediterranean Sea. AB - Diel and seasonal variations in abundance, activity, and structure of particle attached vs free-living bacterial communities were investigated in offshore NW Mediterranean Sea (0-1000 m). Attached bacteria were always less abundant and less diverse but generally more active than free-living bacteria. The most important finding of this study was that the activity of attached bacteria showed pronounced diel variations in the upper mixed water column with higher activities at night. Under mesotrophic conditions, the contribution of attached bacteria to total bacterial activity increased from less than 10% at day time to 83% at night time. At high chlorophyll a concentration, the highest cell-specific activities and contribution to total bacterial activity were due to free-living bacteria at day and to attached bacteria at night. Under summer oligotrophic conditions, free living bacteria dominated and contributed to the most important part of the bacterial activity at both day and night, whereas attached bacteria were much less abundant but presented the highest cell-specific activities. These diel and seasonal variations in activities were concomitant to changes in bacterial community structure, mainly in the upper layer. The number of attached ribotypes was fairly constant suggesting that particles are colonized by a relatively limited number of ubiquitous ribotypes. Most of these ribotypes were also free living ribotypes suggesting that attached bacteria probably originate from colonization of newly formed particles by free-living bacteria in the upper layer. These results reinforce the biogeochemical role of attached bacteria in the cycling of particulate organic carbon in the NW Mediterranean Sea and the importance of diel variability in these processes. PMID- 17345140 TI - Allelopathic effects of toxic haptophyte Prymnesium parvum lead to release of dissolved organic carbon and increase in bacterial biomass. AB - The haptophyte Prymnesium parvum has lytic properties, and it affects coexisting phytoplankton species through allelopathy. We studied the effect of P. parvum allelochemicals on the lysis of the nontoxic and nonaxenic cryptomonad Rhodomonas salina and the consequent release of dissolved organic carbon (DOC). Changes in production, cell density, and biomass of associated bacteria were measured over 12 h. Six different combinations of P. parvum and R. salina cultures, their cell- and bacteria-free filtrates, and growth media as controls were used in the experiments. When P. parvum and R. salina cells were mixed, a significant increase in DOC concentration was measured within 30 min. Bacterial biomass increased significantly during the next 6 to 12 h when R. salina was mixed either with the P. parvum culture or the cell-free P. parvum filtrates (allelochemicals only). In contrast, bacterial biomass did not change in the treatments without the allelopathic action (without R. salina cells). Blooms of P. parvum alter the functioning of the planktonic food web by increasing carbon transfer through the microbial loop. In addition, P. parvum may indirectly benefit from the release of DOC as a result of its ability to ingest bacteria, by which it can acquire nutrients during limiting conditions. PMID- 17345141 TI - Characterization of lysogens in bacterioplankton assemblages of the southern California borderland. AB - Viruses cause significant mortality of marine microorganisms; however, their role in shaping the composition of microbial assemblages has not been fully elucidated. Because viruses may form lysogenic relationships with their hosts, temperate viruses may influence bacterial assemblage structures through direct lysis of hosts when induced by environmental stimuli or by homoimmunity (i.e., immunity to closely related viruses). We investigated the components of bacterioplankton assemblages that bore prophage using the lysogenic induction agent mitomycin C. Seawater was collected at two locations (the San Pedro Ocean Time Series Station and in the Santa Barbara Channel) in the Southern California Borderland and amended with mitomycin C. After 24-h incubation, the community structure of bacterioplankton was compared with unamended controls using automated rRNA intergenic spacer analysis. The addition of mitomycin C to seawater had effects on the community structure of bacterioplankton, stimulating detectable overall diversity and richness of fingerprints and causing the assemblages within incubations to become different to control assemblages. Most negatively impacted operational taxonomic units (OTU) in mitomycin C-amended incubations individually comprised a large fraction of total amplified DNA in initial seawater (5.3-23.3% of amplified DNA fluorescence) fingerprints, and data suggest that these include organisms putatively classified as members of the gamma-Proteobacteria, SAR11 cluster, and Synechococcus groups. The stimulation of assemblage richness by induction of lysogens, and the reduction in the contribution to total DNA of common OTU (and concomitant increase in rare OTU), suggests that temperate phage have the potential to strongly influence the diversity of bacterioplankton assemblages. Because lysogenic OTU may also be resistant to closely related lytic (i.e., free-living) viruses, the impact of lytic virioplankton on assemblages may only be pronounced transiently or when conditions causing lysogenic induction arise. PMID- 17345142 TI - Pilot series of robot-assisted laparoscopic subtotal gastrectomy with extended lymphadenectomy for gastric cancer. AB - BACKGROUND: Robotic surgery is evolving as a therapeutic tool for thoracic and urologic applications; however, its use in gastric cancer surgery has not been extensively reported. The objective of this pilot series was to assess the feasibility of using robotic surgery in performing an extended lymphadenectomy for gastric cancer. METHODS: Between June 2005 and July 2006, seven patients (3 female, 4 male) underwent combined laparoscopic subtotal gastrectomy with omentectomy and robot-assisted extended lymphadenectomy using the da Vinci Surgical System for early distal gastric tumors. The mean age of the patients was 64 years. Tumor staging ranged from 0 to II. Six patients had adenocarcinoma and one patient had a high-grade dysplastic adenoma. RESULTS: All procedures were completed successfully without conversion. The median operating time was 420 min. There was one intraoperative complication requiring a colon resection for a devascularized segment. The median number of nodes harvested was 24 (range = 17 30). Resection margins were negative in all specimens. Patients were hospitalized a median of 4 days (range = 3-9). Thirty-day mortality was 0%. Patients resumed a solid diet a median of 4 days postoperatively. Median followup was 9 (range = 0 10) months. There have been no tumor recurrences to date. CONCLUSION: Extended lymphadenectomy for gastric cancer using robotic surgery is safe and allows for an adequate lymph node retrieval. Our preliminary results suggest that this novel technique offers short hospital stays and low morbidity for patients undergoing surgical resection of distal gastric malignancies. Future studies will be necessary to better define the role of robotic surgery in gastric cancer treatment. PMID- 17345143 TI - Endoscopic ultrasound for the evaluation of Nissen fundoplication integrity: a blinded comparison with conventional testing. AB - BACKGROUND: For patients whose symptoms develop after Nissen fundoplication, the precise mechanism of anatomic failure can be difficult to determine. The authors have previously reported the endosonographic hallmarks defining an intact Nissen fundoplication in swine and the known causes of failure. The current clinical trial tested the hypothesis that a defined set of endosonographic criteria can be applied to determine fundoplication integrity in humans. METHODS: The study enrolled seven symptomatic and nine asymptomatic subjects at a mean of 6 years (range, 1-30 years) after Nissen fundoplication. A validated gastroesophageal reflux disease (GERD)-specific questionnaire and medication history were completed. Before endoscopic ultrasound (EUS), all the patients underwent complete conventional testing (upper endoscopy, esophagram, manometry, 24-h pH). A diagnosis was rendered on the basis of combined test results. Then EUS was performed by an observer blinded to symptoms, medication use, and conventional testing diagnoses. Because EUS and esophagogastroduodenoscopy (EGD) are uniformly performed in combination, the EUS diagnosis was rendered on the basis of previously established criteria combined with the EGD interpretation. The diagnoses then were compared to examine the contribution of EUS in this setting. RESULTS: The technique and defined criteria were easily applied to all subjects. All symptomatic patients had heartburn and were taking proton pump inhibitors (PPI). No asymptomatic patients were taking PPI. All diagnoses established with combined conventional testing were detected on EUS with upper endoscopy. Additionally, EUS resolved the etiology of a low lower esophageal sphincter pressure in two symptomatic patients and detected the additional diagnoses of slippage in two subjects. Among asymptomatic subjects, EUS identified additional diagnoses in two subjects considered to be normal by conventional testing methods. CONCLUSION: According to the findings, EUS is a feasible method for evaluating post-Nissen fundoplication hiatal anatomic relationships. The combination of EUS and EGD allows the mechanism of failure to be detected in patients presenting with postoperative symptoms after Nissen fundoplication. PMID- 17345144 TI - Substance use and sexual behavior during incarceration among 18- to 29-year old men: prevalence and correlates. AB - An A-CASI survey of 197 men with a history of incarceration, ages 18-29, revealed that 50% and 17% of participants, respectively, had used substances or had sex while confined. Univariate regression analyses indicated that these two behaviors were correlated and both were associated with being older, having spent more years incarcerated, being sexual abused, and being involved with gangs and violence during incarceration. Multiple regression analyses showed that the likelihood of any substance use during incarceration was higher for men who were affiliated with a gang. Men were more likely to have had sex during incarceration if they reported having had a male sex partner in the community. The prevalence of sexual behavior also differed across sites. Findings document the occurrence of substance use and sexual behavior among incarcerated men, and highlight the need for continued research into the context of these behaviors. PMID- 17345145 TI - Male circumcision to prevent HIV transmission and acquisition: what else do we need to know? AB - There is growing interest and controversy regarding the promotion of male circumcision (MC) for the prevention of HIV transmission in Africa. Three randomized controlled studies has so far been stopped prematurely as evidence accumulated that showed that circumcision was superior to no circumcision in preventing HIV acquisition among sexually active men in Africa. To some people, the evidence is overwhelming and MC should be promoted aggressively. Others suggest cautious decision making. This paper attempts to review a continuum of perceptions and suggest that the decision to scale-up male circumcision cannot just bebased on randomized controlled trial results. PMID- 17345146 TI - The role of nucleoside transporters in cancer chemotherapy with nucleoside drugs. AB - Nucleoside analogs are important components of treatment regimens for various malignancies. Nucleoside-specific membrane transporters mediate plasma membrane permeation of physiologic nucleosides and most nucleoside analogs, for which the initial event is cellular conversion of nucleosides to active agents. Understanding of the roles of nucleoside transporters in nucleoside drug toxicity and resistance will provide opportunities for potentiating anticancer efficacy and avoiding resistance. Because transportability is a possible determinant of toxicity and resistance of many nucleoside analogs, nucleoside transporter abundance might be a prognostic marker to assess drug resistance. Elucidation of the structural determinants of nucleoside analogs for interaction with transporter proteins as well as the structural features of transporter proteins required for permeant interaction and translocation will lead to "transportability guidelines" for the rational design and therapeutic application of nucleoside analogs as anticancer drugs. It should eventually be possible to develop clinical assays that predict sensitivity and/or resistance to nucleoside anti-cancer drugs and thus to identify those patient populations that will most likely benefit from optimal nucleoside analog treatments. This review discusses recent results from structure/function studies of human nucleoside transporters, the role of nucleoside transport processes in the cytotoxicity and resistance of several anticancer nucleoside analogs and strategies to improve the nucleoside transporter-related anticancer effects of nucleoside analogs. PMID- 17345147 TI - Mental health of rural young adults: prevalence of psychiatric disorders, comorbidity, and service utilization. AB - Few studies estimate rural psychiatric disorder rates. No study has reported either DSM-III-R or DSM IV disorder prevalence and mental health service use among US rural young adults. This paper reports psychiatric disorder prevalence, comorbidity, service utilization, and disorder correlates in a community sample of 536 young adults, aged 19 to 23 years, living in the rural Midwestern US. More than 60% of the sample met criteria for a lifetime disorder. Substance use disorders were most prevalent. Results indicate that young adults living in the rural Midwest demonstrate substantial rates of psychiatric disorder that are comparable to other population groups. PMID- 17345148 TI - Evaluation of a treatment manual for risperidone long-acting injectable. AB - We evaluated the usefulness of a treatment manual to facilitate the use of long acting injectable risperidone in community mental health centers (CMHCs) during an open-label observational study. Perceived clinical utility and clinician adherence to the manual were evaluated. Patient adherence to treatment satisfaction, Clinical Global Impression of Severity (CGI-S) and the Schizophrenia Quality-of-Life Scale (SQLS) were assessed. Mean score for overall utility of the guidebook was 4.2 +/- .6 (scale ratings ranged from 1 = not at all to 5 = extremely). Most clinicians (89-100%) found the guidebook useful, and were adherent to key aspects of appropriate treatment use including concomitant oral risperidone use and injection and dosing parameters for long-acting risperidone. Most patients were adherent to treatment (86.7%), preferred long-acting risperidone over oral risperidone (72.6%) or other oral antipsychotics (78.4%) and were satisfied with long-acting risperidone (90.1%). The open-label observational design limits interpretation of these data. However, in this study manual-supported use of long-acting risperidone was associated with successful implementation of this pharmacologic treatment in the CMHC setting. PMID- 17345149 TI - Achieving global access to heart rhythm therapies in the next decade: a tangible goal. AB - Heart rhythm disorders are a major global public health challenge. This review highlights worldwide inequalities, access to care issues, early experiences with pilot projects, and promotion of global access to modern heart rhythm therapy. PMID- 17345151 TI - Immunogenicity of influenza vaccination in patients with non-Hodgkin lymphoma. AB - PURPOSE: The purpose of this study was to assess humoral response to influenza vaccine in patients (pts) with non-Hodgkin lymphoma (NHL) as compared to healthy subjects (ctrl). PATIENTS AND METHODS: In two epidemic seasons, 2003/2004 and 2004/2005, 163 pts and 92 ctrl were vaccinated. Antibody titers to hemagglutinin (HA) and neuraminidase (NA) were measured in serum samples collected before vaccination, and 1 and 6 months apart. Changes in antibody titers were assessed by comparing geometric mean titers (GMT), mean fold increases (MFI), and seroprotection and seroresponse rates to baseline values. RESULTS: Pts vaccinated in 2003/2004 had, after 1 month, increase in GMT by a factor of 8.64-26.60 for antihemagglutinin antibodies (HI) and 6.93-12.66 for antineuraminidase antibodies (NI), as compared to factor of 9.12-24.41 for HI and 4.83-10.31 for NI in ctrl. At 1 month after vaccination, seroprotection and seroresponse rates were similar in both groups, ranging from 68.42 to 84.21% and 71.93 to 94.74% in NHL, and 66.67-82.22% and 62.22-86.67% in ctrl, respectively. Pts vaccinated in 2004/2005 had increase in the GMT by a factor of 38.76-41.49 for HI and 26.59-30.31 for NI, as compared to factor of 81.19-104.32 for HI and 52.16-54.52 for NI in ctrl. Seroprotection and seroresponse rates were lower in the former group, ranging from 62.11 to 65.26% and 74.47 to 77.66%, respectively. In both seasons, pts achieved titres of antibodies greater than the protective threshold, irrespective of the previous chemotherapy administration. CONCLUSIONS: The results indicate that influenza vaccination induces sufficient immune response in pts with NHL, irrespective of previous chemotherapy. PMID- 17345152 TI - Cervical cancer screening by immigrant and minority women in Canada. AB - Cervical cancer is one of the most preventable forms of cancer and the Pap smear test is one of the most widely accessible forms of cancer screening. An important public health issue is the extent to which Canadian women are engaging in regular screening for cervical cancer, particularly potentially at-risk groups such as recent immigrants and women from minority ethnic backgrounds. We use recent population health surveys to analyze immigrant and native-born women's use of Pap smear testing, with a focus on how screening rates differ by ethnic background and characteristics of immigration. We find that almost all recent immigrant women have markedly lower use of Pap smear testing than comparable Canadian-born women, but these rates slowly increase with years in Canada. However, we find wide variation in rates of screening by ethnic background. Screening rates for White immigrant women from countries where the official language is neither English nor French approach Canadian-born women's utilization rates after 15-20 years in Canada, as do the screening rates of Black and Hispanic women. Screening rates for those from Asian backgrounds remain significantly below native-born Canadian levels even after many years in Canada. As well, immigrant women of Asian background who arrived as children and second-generation Asian Canadians both exhibit significantly lower rates of Pap smear testing than Canadian-born White women. PMID- 17345153 TI - Punjabi immigrant women's breast cancer stories. AB - The breast cancer experiences of Punjabi immigrant women, who represent the most populace group of South Asians in Canada, need to be understood in order to inform culturally appropriate cancer services. The purpose of this qualitative study was to explore women's stories of breast cancer in order to uncover how they made sense of their experiences. Interviews with twelve Punjabi immigrant women who had breast cancer within the last 8 years were available for this study. The four storylines that emerged from the ethnographic narrative analysis were: getting through a family crisis, dealing with just another health problem, living with never-ending fear and suffering, and learning a "lesson from God." A minor theme, "being part of a close-knit family," highlighted the family context as the most pronounced influence on the women's experiences. These findings provide valuable insights into how women's experiences of breast cancer were shaped by the intersections of culture, family, community, cancer treatments, and interactions with health care professionals. PMID- 17345154 TI - A population-based study of maternal and perinatal outcomes associated with assisted reproductive technology in Massachusetts. AB - OBJECTIVE: To assess associations between assisted reproductive technology (ART) and adverse maternal and infant outcomes, with an emphasis on singletons. METHODS: We linked data from the US ART surveillance system with Massachusetts live birth-infant death records data for resident births in 1997-1998 and compared births conceived with ART (N = 3316) with births not conceived with ART or infertility medications (N = 157,066) on: maternal chronic conditions, pregnancy complications, labor and delivery complications, and perinatal and infant outcomes. RESULTS: Overall, ART was strongly associated with numerous adverse outcomes. The magnitude was reduced for several outcomes when analyses were limited to singletons. After further exclusion of maternal subsets with rare ART births (maternal age <20; education 4) and (1-->6)-glycosidic bonds. Thus, the main chain of the galactomannan was found to consist of (1-->4)-linked mannoypyranosyl units having beta-glycosidic bonds while (1-->6)-linked alpha-glycosidically bonded galactopyranosyl units form the branching points. PMID- 17345317 TI - Structural characterization of anti-complementary polysaccharides from the leaves of Artemisia princeps. AB - Structural characterizations of the anti-complementary acidic heteroglycans, AAF IIb-2 and IIb-3, obtained from the leaves of Artemisia princeps pamp have been studied. AAF IIb-2 consists of rhamnose, xylose, arabinose, galactose, glucose and uronic acids (glucuronic acid and galacturonic acid) in the molar ratio of 7.6:7.6:13.0:10.9:3.0:57.9, and AAF IIb-3 consists of the same sugars in the ratio of 3.9:2.6:24.7:19.7:2.6:46.5. Methylation analysis including carboxyl reduction and also selective enzymolysis using EXO-alpha- L-arabinofuranosidase suggested that AAF IIb-3 has a main chain consisting of (1-->4)-linked galacturonic acid and (1-->2)-linked rhamnose mostly substituted at the O-4 position. AAF IIb-3 also contained arabino-3,6-galactan moiety and most of the arabinose was present as an alpha- L-furanosyl residue in the non-reducing terminals and highly branched side chains which mostly attached to the O-3 position of (1-->6)-linked galactopyranosyl residue. The basic structure of AAF IIb-2 is similar to that of AAF IIb-3, but IIb-3 has a higher arabinogalactan content than IIb-2. PMID- 17345318 TI - Macrocarposide, a new isoflavanone c-glucoside from Pterocarpus macrocarpus heart wood. AB - Macrocarposide has been isolated for the first time as a natural product from the heartwood of Pterocarpus macrocarpus along with some known compounds. Based on its spectral and chemical evidence, it has been assigned the structure dalbergioidin-6- C-glucoside ( 1). PMID- 17345319 TI - Constituents of Shashen (Adenophora axilliflora). AB - From the ethyl acetate extract of the Chinese drug "Shashen", the root of Adenophora axilliflora Borb., three triterpenoids, cycloartenol acetate ( 1), lupenone ( 2) and beta-sitosterol ( 3), two triterpenoid derivatives, beta- D glucopyranosyl-(1-->3)-beta-sitosterol ( 7) and its 6- O-palmitoyl ester ( 6), along with two coumarins, (+)-praeruptorin A ( 4) and 3'-angeloyl-4'-isovaleryl (3' S, 4' S) CIS-khellactone ( 5) have been isolated. A detailed (1)H-NMR analysis of compounds 6, 7 and their acetates is reported. The structure of the partial hydrolysis product of 5 is revised on the basis of spectroscopic evidences and mechanistic considerations. PMID- 17345320 TI - Studies on the tissue culture of Stevia rebaudiana and its components; (II). Induction of shoot primordia. AB - Shoot primordia, which were able to propagate vegetatively with a very high rate and to redifferentiate easily to new plants, were induced from shoot tips of Stevia rebaudiana Bertoni on Gamborg B5 medium containing 6-benzylaminopurine (BAP) and alpha-naphthaleneacetic acid (NAA) under light. The propagation of the shoot primordia of Stevia rebaudiana is rapid, and they are highly stable in chromosome number and karyotype. The shoot primordia can propagate at a high rate for a long time without differentiation. At any time, the shoot primordia readily developed into plantlets with shoots and roots within 2 or 3 weeks in static culture on B5 medium containing 0.02 mg/l BAP and 2% sucrose. The plantlets were transplanted to sterilized soil to grow to normal adult plants. PMID- 17345322 TI - Isolation and 1H/13C-NMR Studies on 19,20-Dihydrocondylocarpine: An Alkaloid from the Leaves of Ervatamia coronaria and Alstonia scholaris. AB - Studies on the alkaloidal constituents of the leaves of Ervatamia coronaria Stapf and Alstonia scholaris have resulted in the isolation of (20 S)-19,20 dihydrocondylocarpine which has not been previously reported from these plants. The stereochemistry at C-20 was established with the help of n. O. e. difference measurements. (13)C-NMR assignments have been made by polarisation transfer techniques. PMID- 17345323 TI - Loganin and new iridoid glucosides in Gentiana pedicellata. AB - 2'- P-Coumaroyl-loganin, 2'-feruloyl-loganin, 2'-caffeoyl-loganin, and the known iridoid loganin have been isolated from flowers and leaves of Gentiana pedicellata (Gentianaceae). This is the first occurrence of iridoid glucosides being reported in this species. PMID- 17345324 TI - A new triterpene ester, an anthraquinone and other constituents of the fern Lygodium flexuosum. AB - Lygodium flexuosum, a fern reported to exhibit antifertility activity, has been found to contain a new compound characterized as O- P-coumaryl-dryocrassol, besides dryocrassol itself, tectoquinone, kaempferol, kaempferol-3-beta- D glucoside, beta-sitosterol, and stigmasterol. PMID- 17345325 TI - New pseudoguaianolides from Gaillardia megapotamica var. scabiosoides. AB - The aerial parts of Gaillardia megapotamica var. scabiosoides afforded known pseudoguaianolides and three new ones. Furthermore, a new guaianolide and an acetylenic sulfoxide were isolated. PMID- 17345326 TI - The essential oil in lamina and petiole of Heracleum dissectum leaves. AB - The essential oils of lamina and petiole of Heracleum dissectum are described. Fifty-seven compounds have been identified by mass spectrometry and retention indices. Differences between the oils of the two organs were mainly quantitative. PMID- 17345327 TI - Contribution to the study of the essential oil from Thymus tosevii growing wild in Greece. AB - The essential oil of Thymus tosevii Velen. (Lamiaceae) growing wild in Greece was investigated by means of GLC, GC-MS, and the physico-chemical constants were determined. The essential oil content was 0.9%. As main constituents resulted linalool 35.5% and geraniol 27.5%. In addition twelve monoterpene hydrocarbons, nine oxygen containing compounds, one sesquiterpene, and two terpene esters were identified, making up about 98% of the oil. PMID- 17345331 TI - The volatile oils of some endemic thymus species growing in southern anatolia. PMID- 17345330 TI - Two new pseudobenzylisoquinoline alkaloids: berbithine and dihydrotaxilamine. PMID- 17345332 TI - Erythrina Studies; Part 3. Isolation of an isoflavone from Erythrina senegalensis and Erythrina excelsa. PMID- 17345333 TI - Chemical constituents of the stem heart wood of Stereospermum kunthianum. PMID- 17345336 TI - [Demethoxyencecalin and Thymol derivatives from Arnica sachalinensis1.]. AB - From the flowers of ARNICA SACHALINENSIS the chromene desmethoxyencecalin, 10 acetoxy-8,9-epoxy-3- O-isobutyrylthymol, and 10-acetoxy-8-hydroxy-9 isobutyryloxythymol were isolated and their structures established by mass spectrometry (13)C-, and (1)H-NMR spectroscopy. PMID- 17345337 TI - Ehrenoside, a New Phenylpropanoid Glycoside from Veronica bellidioides1. AB - From the methanolic extract of the whole plant of VERONICA BELLIDIOIDES L., ehrenoside, a new phenylpropanoid glycoside has been isolated. The structure of this compound has been elucidated on the basis of chemical and spectral data as 3, 4-dihydroxy-beta-phenylethoxy- O-alpha- L-arabinopyranosyl-(1 --> 2)-alpha- L rhamnopyranosyl-(l --> 3)-4- O-caffeoyl-beta D-glucopyranoside ( 1). PMID- 17345338 TI - [Dihydropenstemide from Penstemon confertus and the Preparation of epi Dihydropenstemide from Penstemide.]. AB - From leaves of PENSTEMON CONFERTUS Dougl. a valeriana-type ester iridoid has been isolated and structurally elucidated as dihydropenstemide by spectroscopic methods. Catalytic hydrogenation of penstemide provides a new compound, identified as 8- EPI-dihydropenstemide. PMID- 17345339 TI - Structure of Undulatin: A New Iridoid Glucoside from Tecomella undulata. AB - Undulatin ( 1), a new iridoid glucoside isolated from the TECOMELLA UNDULATA Seem. (Bignoniaceae), has been assigned the structure 4'- O-P-coumaroyl-7,8 dihydro-8-dehydroxymethylbartsioside by chemical and spectroscopic analysis. PMID- 17345340 TI - The structure and the stereochemistry of atractyliretin. AB - The nor-kaurane diterpene Atractyliretin was obtained by acid hydrolysis of Atractyloside, a toxic substance isolated from ATRACTYLIS GUMMIFERA L (Compositae). On the basis of spectral (IR, (1)H-NMR, (13)C-NMR and MS) analysis and chemical degradation its structure and stereochemistry was identified as 4. PMID- 17345341 TI - New Guaianolides and Farnesol Derivatives from Arctotis arctotoides1. AB - The aerial parts of ARCTOTIS ARCTOTOIDES afforded eight known sesquiterpene lactones and three new ones, the 11beta,13-dihydroguaianolides 9 and 10 as well as the chlorohydrine 8. Furthermore two 2Z-farnesol derivatives 12 and 13 were isolated. The structures were elucidated by highfield (1)H-NMR. The stereochemistry of several compounds has been revised. PMID- 17345342 TI - The Essential Oil of Salvia lavandulifolia Subspecies Oxyodon. A Study of its Vegetative Cycle. AB - The qualitative and quantitative variations in the essential oil of the OXYODON subspecies of SALVIA LAVANDULIFOLIA Vahl were studied - throughout its complete vegetative cycle (March 1983 to February 1984). Spasmolytic activity of the essential oil was selected as a characteristic warrenting more in depth study. Major components of the essential oil were found to be camphor and 1, 8-cineole, whereas only trace quantities of thujones could be detected at any time in the plant's vegetative cycle. Spasmolytic activity was most intense in May (the flowering period) and lowest in July. PMID- 17345345 TI - [Cardiotonically Active Principles from Spigelia anthelmia1.]. AB - From the upper parts of SPIGELIA ANTHELMIA L. besides some widely distributed phenolcarboxylic acids and flavonoids two volatile alkaloids have been isolated and identified as isoquinoline and an iridoid compound of the actinidine type. In the water extract choline, benzoylcholine and 3,3-dimethyl-acryloylcholine could be identified. Preliminary pharmacological investigations revealed that the alkaloids are involved in the cardiotonic activity of the plant. PMID- 17345346 TI - Molluscicidal Saponins of Xeromphis spinosa. AB - From the ethanolic extract of the defatted leaves of XEROMPHIS SPINOSA (Thunb.) Keay two new oleanolic acid based glycosides have been isolated and characterized with the help of FABMS, (13)C-NMR and chemical studies. PMID- 17345347 TI - Fast and Selective Assay of l-Ascorbic Acid in Rose Hips by RP-HPLC Coupled with Electrochemical and/or Spectrophotometric Detection. AB - A simple, fast, and selective method for the assay of L-ascorbic acid in rose hips was developed using RP-HPLC. Ascorbic acid was extracted with 2% metaphosphoric acid and sample clean-up was optimized with C18 disposal extraction cartridges. Use of 0.5% metaphosphoric acid as the mobile phase completely suppressed the dissociation of ascorbic acid. Sufficient retention was achieved so that the addition of ion-pairing agents was not necessary. The column effluent was monitored by spectrophotometric (242 nm) and electrochemical detectors (550 mV vs Ag/AgCl); the electrochemical detector was found to be both more selective and more sensitive. By coup-ling the two detectors in series, a true two channel detection with on-line validation was achieved. Reproducible results (r.s.d. 1-4%) were obtained from assays of several commercially available products, as well as from fresh rose hips, and revealed considerable differences in ascorbic acid content, ranging from 0.03 to 1.3%. PMID- 17345348 TI - Formation of Artemisinin in Artemisia annua During One Vegetation Period*,1. AB - In order to investigate the possibility of isolating greater amounts of the antimalarial compound artemisinin (quinghaosu), plants of ARTEMISIA ANNUA were cultivated and analysed at different stages of development. We found the highest content just before flowering. It was also possible to correlate development of the plants with the maximum content of artemisinin. ARTEMISIA ANNUA plants cultivated from various other sources were also examine for artemisinin content. According to our results, none of these plants contained sufficient amounts of artemisinin to justify an isolation on a technical scale. Furthermore other Artemisia species were tested. We found artemisinin in only one other species. To possibly increase the amount of artemisinin during the growth period of the plant, we tested two hormone-type growth regulators on A. ANNUA strain 811. The results showed that one of them, chlormequat, was able to increase the artemisinin content by 30% over untreated plants. We also found some slight effects of the growth regulators on morphological criteria of glandular trichomes. PMID- 17345349 TI - Reinvestigation of the Alkaloid Composition of Atropa belladonna Plants, Root Cultures, and Cell Suspension Cultures. AB - The alkaloid composition of ATROPA BELLADONNA was analyzed by high resolution GLC and GLC-MS. A total of 13 alkaloids, most new for ATROPA, were identified from roots. The aboveground parts of the plant revealed 7 alkaloids; the hygrines were completely absent. The alkaloid pattern of root cultures was almost identical with the pattern of roots from intact plants. The patterns differed only quantitatively. Scopolamine which in A. BELLADONNA seems to be synthesized in the roots only, was preferably excreted into the culture medium. Norhyoscyamine was found frequently in plant shoots. The occurrence of hyoscyamine N-oxide in various plant organs could be confirmed. Cell suspension cultures produced trace amounts of hyoscyamine, 3alpha-acetoxytropane and 3alpha-tigloyloxytropane. The last two ester alkaloids were not detectable in intact plants. PMID- 17345350 TI - Biosynthesis of phenylalanine and tyrosine in claviceps. AB - Some enzymes of the terminal steps of phenylalanine and tyrosine biosyntheses were investigated in various alkaloid-forming ergot strains. All strains studied utilize both arogenate and phenylpyruvate as an intermediate in L-phenylalanine synthesis. L-Tyrosine is preferentially or exclusively synthesized via the arogenate pathway. No feedback inhibition of arogenate pathway enzymes by aromatic amino acids was observed. PMID- 17345351 TI - [Further Compounds from Centaurea stoebe.]. AB - From CENTAUREA STOEBE the following compounds have been isolated: cnicin, salonitenolide, salonitenolid-8- O-(4'-acetoxy-5'-hydroxyangelate), stoebenolide, 3-hydroxy-2-methylbutyrolactone, and 3-(3, 4-dihydroxy-5-methoxyphenyl)-prop-1-yl 3-hydroxy-11-methyloctadecanoate. PMID- 17345352 TI - Bisabolone derivatives and sesquiterpene lactones from centaurea species. AB - The investigation of three CENTAUREA species collected in Argentina afforded, in addition to several known sesquiterpene lactones, a new guaianolide, a germacranolide, and two bisabolone derivatives. The structures were elucidated by highfield (1)H-NMR spectroscopy. PMID- 17345353 TI - Methylated Flavones from Teucrium polium. AB - The following four methylated flavones were obtained from the leaves of TEUCRIUM POLIUM L. (Labiatae). 4', 5-dihydroxy-6,7-dimethoxyflavone (cirsimaritin); 3', 5 dihydroxy-4',6,7-trimethoxyflavone (eupatorin); 5-hydroxy-4',7-dimethoxyflavone (apigenin-4', 7-dimethylether); 4', 5, 3'-trihydroxy-6,7-dimethoxyflavone (cirsiliol). One of these (4', 5-dihydroxy- 6,7-dimethoxyflavone) has been already reported in the same plant by Brieskorn and Biechele (1). PMID- 17345354 TI - Isolation of a Highly Sweet Constituent from Cinnamomum osmophloeum Leaves1. AB - The sweetness of the leaf sample of the Taiwanese species, CINNAMOMUM OSMOPHLOEUM, was traced by activity-guided fractionation to its major volatile oil constituent, TRANS-cinnamaldehyde. Cinnamaldehyde represents a further class of intensely sweet compounds of plant origin. PMID- 17345355 TI - Molluscicidal and antifungal activity of diterpenoids from brown algae of the family dictyotaceae. AB - 17 diterpenoids isolated from brown algae of the family DICTYOTACEAE have been evaluated for molluscicidal and antifungal activity. Significant molluscicidal activity is exhibited by the two geometrical isomers 9 and 10. The assessment of structure-activity relationships has been considered. PMID- 17345357 TI - A Novel Phenalenone from Salvia moorcraftiana. PMID- 17345358 TI - Aesculuside-A, A New Triterpene Glycoside from Aesculus indica. PMID- 17345359 TI - Further Dibenzocyclooctadiene Lignans from Roots and Stems of Kadsura longipedunculata. PMID- 17345360 TI - Further beta-Cyperone Derivatives from Haplopappus freemontii. AB - The roots of HAPLOPAPPUS FREEMONTII afforded in addition to the known 8-oxo-beta cyperone two further derivatives. The structures were elucidated by highfield (1)H-NMR spectroscopy. PMID- 17345361 TI - Nebenalkaloide aus Aconitum longtounense. PMID- 17345362 TI - Struktur des Helicidols, eines weiteren beta-Allopyranosids aus Helicia erratica. PMID- 17345363 TI - Sterols in Callus Cultures of Solanum mammosum. PMID- 17345364 TI - Alkaloids of Fumaria bracteosa. PMID- 17345365 TI - Optimizing the mobile phase for separation of phosphatidylcholine and phosphatidylethanolamine in soybean lecithin. PMID- 17345366 TI - Lecithin of Glycine max: Dietary Source of Balanced Essential Fatty Acids. PMID- 17345367 TI - Lecithin as medicinal substance and adjuvant in pharmacy. PMID- 17345368 TI - Interactions of liposomal drug carriers with cells. PMID- 17345369 TI - Pilot scale axenic mass cultivation of microalgae I. Development of the biotechnology. PMID- 17345370 TI - Elicitor-Induction of Sanguinarine Formation in Papaver somniferum Cell Cultures and Semicontinuous Sanguinarine Production by Re-Elicitation. PMID- 17345371 TI - [A Useful Aid for Isolation of Enzymes and other Biopolymers from Brown Algae.]. PMID- 17345372 TI - Pilot Scale Axenic Mass Cultivation of Microalgae II. Sterols of Blue-Green Algae (Cyanobacteria). PMID- 17345373 TI - Highly Efficient 12beta-Hydroxylation of Digitoxin in Digitalis lanata Cell Suspensions Using a Two-staged Culture Method. PMID- 17345374 TI - Hemimycin, a New Antibiotic from two Hemimycena Species (Basidiomycetes). PMID- 17345375 TI - Metabolism of C-21 Steroids in Urginea maritima. PMID- 17345376 TI - Metabolism and Enzymology of Isoflavone Malonylglucosides and Pterocarpan Phytoalexins in Cicer arietinum. PMID- 17345377 TI - Effect of Trace Elements on Cardiac Glycosides Accumulation in Digitalis grandiflora. PMID- 17345378 TI - Bioconversion of Chromene Derivatives in Seedlings of Ageratina adenophora. PMID- 17345379 TI - Geraniol-10-hydroxylase of Catharanthus roseus and its Correlation with Indole Alkaloid Biosynthesis. PMID- 17345380 TI - Derivation of Diagnostic 1H-NMR Parameters Applicable to the Structure Elucidation of Procyanidins. PMID- 17345381 TI - Mass Spectrometric Identification of Olefinic Terpene Hydrocarbons by Derivatization and GC/MS Analysis. PMID- 17345382 TI - HPLC-Screening of Naturally Occurring Salicylates. PMID- 17345383 TI - Isolation, Structure Elucidation and Analysis of New Acetylenic Constituents from Echinacea angustifolia. PMID- 17345384 TI - Rotachrom new possibilities for analytical separation techniques. PMID- 17345385 TI - Herbal medicine in america. PMID- 17345386 TI - The Aklaloid Content of Senecio nemorensis, ssp. nemorensis and Senecio nemorensis, ssp. fuchsii. PMID- 17345387 TI - Topical antiphlogistic activity of the saponin quercilicoside-a and its genin. PMID- 17345388 TI - Flavonol Glycosides of Arnicae Flos DAB 9. PMID- 17345389 TI - Investigation of Pyrrolizidine Alkaloids in Plant Material by Means of Positive Ion and Negative Ion Chemical Ionization GC-MS. PMID- 17345390 TI - Immunomodulatory Activity of an Aqueous Extract of the Stem Bark of Azadirachta indica. PMID- 17345391 TI - Immunologically Active Polysaccharides from Tissue Cultures of Echinacea purpurea. PMID- 17345392 TI - A New Antifungal Chromene and a Related Di-chromene from Hypericum revolutum. PMID- 17345393 TI - Metabolism of C-9-14C-Rhein. PMID- 17345394 TI - Antiinflammatory Activity of Conyza canadensis. PMID- 17345395 TI - Irritant and antineoplastic principles of some species of the genus jatropha (euphorbiaceae). PMID- 17345396 TI - Anti-Tumor Properties of Eupatoriopicrin; in vivo Test Models and Results. PMID- 17345397 TI - Anti-sickling Properties of Cajanus cajan: Effect on Haemoglobin Gelation and Oxygen Affinity. PMID- 17345398 TI - Eugenol and analogues as antiplatelet compounds. PMID- 17345399 TI - Larvicidal Effects of Six Amide Alkaloids from Piper guineense. PMID- 17345400 TI - Interceptive plants. PMID- 17345408 TI - Complex Acetylenes from the Roots of Ferula communis. AB - The benzene extract from the roots of FERULA COMMUNIS afforded the coumarin ferulenol ( 1) and the structurally related acetylenes named ferulinolone [3-(1,2 dihydrofalcarinolonyl)-ferulenol] ( 4) and decarboxyferulinolone [2-nor-3-(1,2 dihydrofal-carinolonyl-ferulenol] ( 7). The structures of these substances were deduced from their spectral data and those of their derivatives, mainly from the (1)H- and (13)C-NMR 1D and 2D spectra (one bond and long-range correlations). Methoxylatifolone ( 10) was also isolated from this extract. PMID- 17345409 TI - Oxypeucedanin, a Major Furocoumarin in Parsley, Petroselinum crispum. AB - Fresh parsley leaves and roots were analyzed by HPLC and photobiological assay for photoactive furocoumarins. Oxypeucedanin ( 7), not previously reported from parsley, was found to be the major component (70-100 ppm wet weight). Although only moderately photoactive, its high concentration in parsley may be partially responsible for contact photodermatitis. Other photoactive compounds, namely 5 MOP ( 2), 8-MOP ( 3), psoralen ( 1), isopimpinellin ( 4) and imperatorin ( 5) were also present and quantified. PMID- 17345412 TI - Improvement of Diosgenin Yield from Dioscorea deltoidea Plant Cell Cultures by Use of a Non-Traditional Hydrolysis Method. AB - The attractiveness of fermentor cultures of DIOSCOREA DELTOIDEA Wall. (Dioscoreaceae) as a source of diosgenin has been greatly improved by switching away from the traditional product recovery method that has been used in all previous studies. By using a known but little-used hydrolysis method involving 2N H (2)SO (4) in 70% isopropanol rather than using 2N aqueous HCl, diosgenin was found to be a growth-associated product instead of a non-growth-associated product as was formerly thought. This is an important improvement from a biotechnological standpoint because it means that diosgenin can be obtained directly from growth-phase tissue and that a non-growth phase is unnecessary. The reason that switching hydrolysis methods has this impact is that the non traditional method gives high diosgenin yields from a broader group of steroidal glycosides. During the non-growth phase, steroidal glycosides were found to spontaneously change from furostanol saponins to spirostanol saponins. Whereas the nontraditional hydrolysis method gives high diosgenin yields from both types, the traditional method gives high yields only from the latter type. PMID- 17345413 TI - Long-Term Cultivation of Digitalis lanata Clones Propagated in Vitro: Cardenolide Content of the Regenerated Plants1. AB - Shoot cultures of DIGITALIS LANATA Ehrh. (Scrophulariaceae) were established by inoculating meristem explants from axillary buds in a halfstrength liquid Murashige and Skoog medium. After short- and long-term cultivation IN VITRO, the shoots were rooted on a solid medium, transferred into soil, and grown in the greenhouse. The cardenolide content of the regenerated plants was determined by HPLC. The vegetatively propagated plants showed good homogeneity and are identical with the parent plant in terms of their digoxigenin-glycoside content. Long-term cultivation IN VITRO had no negative influence on the homogeneity and digoxigenin-glycoside content of the propagated plants. With this method, valuable genotypes can be preserved for a longer time than the natural vegetation period. PMID- 17345415 TI - [Pyrrolizidine Alkaloids from Emilia sonchifolia.]. AB - The pyrrolizidine alkaloids, senkirkine ( 1) and doronine ( 2) were isolated from the aerial parts of EMILIA SONCHIFOLIA. PMID- 17345416 TI - Contribution to the Study of Plectranthus fruticosus Leaf Essential Oil. AB - The essential oil of PLECTRANTHUS FRUTICOSUS L'Herit. (Labiatae) is shown to contain at least fifty components, among which the major one, i.e. sabinyl acetate, accounts for more than 60% of the total. To our knowledge, this compound is described in Labiatae at such a high concentration for the first time. A preliminary study on rats reveals that this essential oil is teratogenic and/or highly foetotoxic. PMID- 17345417 TI - Composition of Aloysia gratissima Flower Essential Oil1. AB - Globulol, sabinene, caryophyllene, and caryophyllene epoxide have been isolated and identified in the essential oil of A. GRATISSIMA flowers from plants growing in Uruguay. PMID- 17345419 TI - Triterpenoids from Roots and Stems of Kadsura coccinea. AB - 24-Methylenecycloartenone ( 1), kadsuric acid ( 2) and a new triterpenoid acid named coccinic acid ( 3A) were isolated from the ether soluble fraction of the dried roots and stems of KADSURA COCCINEA. PMID- 17345420 TI - Henricine, a New Tetrahydrofuran Lignan from Schisandra henryi. AB - A new tetrahydrofuran lignan, named henricine ( 1), was isolated from the stems of SCHISANDRA HENRYI. High resolution COSY spectrum was used in the structural elucidation. PMID- 17345421 TI - 3beta, 22-Dihydroxylanosta-7,9(11), 24-triene: A New, Minor Compound from Inonotus obliquus. AB - The present paper deals with the isolation and structural elucidation of a new triterpene diol with the lanostane skeleton. The structure of the compound was confirmed to be 3beta, 22-dihydroxylanosta-7,9(11), 24-triene on the basis of spectroscopic data. PMID- 17345422 TI - Two New Steroidal Glucuronides from Solanum lyratum, II1. AB - Two new steroidal glucuronides of a furostanol and of a spirostanol derivative along with two known glycosides, SL-a and tigogenin 3- O-beta- D-glucopyranoside, were isolated from the aerial parts of SOLANUM LYRATUM. PMID- 17345424 TI - Sativanine-H: A New Alkaloid from the Bark of Zizyphus sativa. PMID- 17345426 TI - A New Flavone from Sapium insigne. PMID- 17345425 TI - A New Neo-Lignan, A Prostaglandin I2 Inducer from the Leaves of Zizyphus jujuba. PMID- 17345427 TI - Neosenkirkine from Senecio leptolobus. PMID- 17345428 TI - Flavonoids and Alkaloids from Chamaecytisus eriocarpus. PMID- 17345429 TI - Constituents of the Essential Oil of Clausena anisata Leaves. PMID- 17345430 TI - The Essential Oil of Dorystoechas hastata. PMID- 17345432 TI - An inducible saponine cleaving glycosidase from fusarium and its application to the production of solasodine. PMID- 17345431 TI - Experiments on Cultures of Inonotus obliquus. PMID- 17345433 TI - 9-hydroxymarasmic Acid, a new natural occurring sesquiterpene. PMID- 17345434 TI - Defence Mechanisms of Tomato Plants (Lycopersicon spp.) against Botrytis cinerea Involving Volatiles with Morphogenetic Activity. PMID- 17345435 TI - Variation of Fumarprotocetraric and Protocetraric Acids in Cetraria islandica and C. ericetorum. PMID- 17345436 TI - Effects of Plant Bioregulators on Valepotriate Production of Cell Suspension Cultures of Valeriana wallichii and Fedia cornucopiae. PMID- 17345437 TI - Va-Mycorrhiza in Gentiana lutea, the Importance of Cultivation and Influence on Constituents. PMID- 17345438 TI - Production of beta-Methyldiginatin by Digitalis Cell Cultures. PMID- 17345439 TI - In Vitro-Cultures of Arctostaphylos-Species. III: Phytochemical Comparison of in Vitro-Cultures and Outdoor Plants. PMID- 17345440 TI - Fructan-Synthesis in Cell Cultures of Symphytum officinale. PMID- 17345441 TI - Co-Cultivation of Digitalis purpurea and Digitalis lanata Cell Cultures. PMID- 17345442 TI - Reinvestigation of the Alkaloid Composition of Atropa belladonna Plants, Root Cultures and Suspension Cultures. PMID- 17345443 TI - Optimization of some Parameters in Cultivating Scopolamine-producing Cells of Hyoscyamus muticus. PMID- 17345445 TI - The N-oxides of pyrrolizidine alkaloids: specific uptake by cells, protoplasts and vacuoles from senecio cell cultures. PMID- 17345444 TI - Alkaloid Production by Hordeum vulgare Cell Cultures. PMID- 17345446 TI - Bioconversion of Morphine by Cell Suspensions of Ginkgo biloba Growing in vitro. PMID- 17345447 TI - Effects of m-Fluorotyrosine on Growth and Betacyanin Levels of Betalain Forming Plant Cells. PMID- 17345448 TI - Chemotypes of tansy in Finland. PMID- 17345449 TI - Long-Term-Storage of Coleus blumei Suspension Cultures and Cryopreservation of Callus. PMID- 17345451 TI - Bioynthesis of Vitexin and Isovitexin: C-Glycoxylation of Flavonoid Intermediates with Cell Free Preparation from Fagopyrum esculentum. PMID- 17345450 TI - Variation of Flavonoids in Allium cepa. PMID- 17345452 TI - Influence of Sulfur and Nitrogen Fertilization on Alkaloid Content of Atropa belladonna. PMID- 17345453 TI - Pyrrolizidine Alkaloids of Senecio vulgaris are Synthesized as N-Oxides in the Roots. PMID- 17345454 TI - Yield, Yield Components and Seed Quality of Linum Mutants under Constant Environmental Conditions in Phytotron. PMID- 17345455 TI - Results of the Analysis of the Thebaine Contents of Capsules and Roots from Different Clones of Papaver bracteatum. PMID- 17345457 TI - Schwermetallbelastung von Arzneidrogen und deren Zubereitungen. PMID- 17345456 TI - Investigations in Cultivation Abilities and Seed Quality of Oenothera biennis. PMID- 17345458 TI - Micropropagation of Coluria geoides by Axillary Shoots. PMID- 17345459 TI - Isolation and Characterization of Lenticellarine, a Novel Alkaloid from Dysozylum lenticellare. PMID- 17345460 TI - Ipobscurines, Non-ergoline Type Indole Compounds from the Seeds of Ipomoea obscura. PMID- 17345461 TI - New Alkaloids from Crinum asiaticum. PMID- 17345462 TI - A New Alkaloid from Psychotria forsteriana. PMID- 17345463 TI - Synthesis of acridonderivatives as biological active substances and natural occuring alkaloids in rutaceae species. PMID- 17345464 TI - A New Alkaloid from the Bark of Zizyphus sativa. PMID- 17345465 TI - Some Flavonoid Compounds of Salvia candelabrum. PMID- 17345466 TI - Flavone Glycosides of Sideritis incana. PMID- 17345467 TI - 4', 4'''-Dimethoxy Cupressuflavanone, a New Biflavanone from Eupatorium subhastatum. PMID- 17345468 TI - Flavonoid Aglycones of Thymus moroderi. PMID- 17345470 TI - Methylated Flavonoids in the Leaf Resin of Cistus albanicus and C. parviflorus. PMID- 17345469 TI - A New Neolignan Glycoside from Sambucus racemosa. PMID- 17345471 TI - Flavonoids and Sesquiterpene Lactones, Constituents of Centaurea alexandrina. PMID- 17345472 TI - Spectroscopic Study of Caffeoylquinic Acid Derivatives of Cynara scolymus. PMID- 17345473 TI - Characterization of tannins from rhatany root. PMID- 17345474 TI - The first Naturally Occuring Esters in Aloin-type Glycosyls. PMID- 17345476 TI - Essential Oil from Sideritis funkiana. PMID- 17345475 TI - Content of Phenolic Acids in Leaves of Menyanthes trifoliata. PMID- 17345477 TI - Composition of the Volatile Oils from the Roots, Leaves and Fruits of Different Taxa of Apium graveolens. PMID- 17345478 TI - Analysis of the Essential Compounds of Hypericum perforatum. PMID- 17345479 TI - HPLC screening of constituents from eupatorium species by diode array detection. PMID- 17345480 TI - Prefractionation of Essential Oils using Silica Gel "Mini Extraction Columns". PMID- 17345481 TI - Composition of the Essential Oil of Polylophium involucratum. PMID- 17345482 TI - OPLC Analysis of Closely Related Furocoumarins. PMID- 17345483 TI - A Comparison of Circular and Linear OPLC Separations of Naturally-Occurring Compounds. PMID- 17345484 TI - Rotachrom-analytical separations of naturally occuring compounds. PMID- 17345485 TI - [(Rapid and reproducable isolation of natural procyanidins by droplet counter current chromatography).]. PMID- 17345486 TI - Phototoxic furanocoumarins. PMID- 17345487 TI - New Perceptions of PMR Measurements of the Peracetates of 4-R-Configurated 4 to 6 Linked Procyanidins. PMID- 17345488 TI - Spectrophotometric Determination of Sesquiterpenlactone (S1) in "Arnicae flos DAB 9" with m-Dinitrobenzene. PMID- 17345489 TI - A convenient method for the quantitative determination of mucilage polysaccharides in althaeae radix. PMID- 17345490 TI - Structure and anti-hypertensive properties of nitidine chloride from fagara species. PMID- 17345491 TI - Assay of Total Vitamin C in Rose Hips by RP-HPLC using a Post-Column Reduction System for the Determination of Dehydroascorbic Acid. PMID- 17345492 TI - Some Pharmacological Actions of Mikania cordata. PMID- 17345493 TI - Effect of the quality of dietary fat on the hypertensive effect of salt and on tissue Fatty Acid composition in spontaneously hypertensive rats. PMID- 17345494 TI - Pharmacological Study of Santolina chamaecyparissus. I. Acute Toxicity, Antiinflammatory and Antiulcer Activity. PMID- 17345495 TI - Anti-Inflammatory and Antipyretic Activities of Syzygium cuminii. PMID- 17345496 TI - Anti-Inflammatory Activity of a Flavone from Sideritis leucantha. PMID- 17345497 TI - Antidepressant activity of selected natural products. PMID- 17345498 TI - First data on the percutaneous absorption of a topically active antiphlogistic flavonoid. PMID- 17345499 TI - Pharmacological Activity of Mentha piperita, Salvia officinalis and Rosmarinus officinalis Essences on Oddi's sphincter. PMID- 17345500 TI - Application of in vitro Enzyme Study (PDE) in Forecasting the Biological Activity of Plants. PMID- 17345501 TI - Utero-Contracting Triterpene Saponins from Ardisia crispa. PMID- 17345502 TI - Studies on the Acivity of Crataegus Compounds upon the Isolated Guinea Pig Heart. PMID- 17345503 TI - The effect of different combinations of extracts from plants on the lithogenic properties of rat bile. PMID- 17345504 TI - Neuropharmacological Studies on Pluchea indica. PMID- 17345505 TI - Phytochemical- and Pharmacological Investigation of the Biologically Active Fraction from the Flowers of Vernonia amygdalina. PMID- 17345506 TI - Preliminary Report on the Bronchodilator Properties of the Aqueous Stem Bark Extract of Sterculia foetida. PMID- 17345507 TI - Cytotoxic Activity of some Derivatives of Grosheimia macrocephala. PMID- 17345508 TI - The Examining of Isolated Tannins and their Astringent Effect. PMID- 17345509 TI - 5-lipoxygenase-inhibitors from medicinal plants. PMID- 17345510 TI - Screening of Essential Oils and Phenolic Compounds for in vitro- Inhibition of Prostaglandin Biosynthesis. PMID- 17345511 TI - The Calcium Antagonistic Activity of Peucedanum palustre. PMID- 17345512 TI - Inhibition of TSH-effects by Plant Extracts and Phenolic Plant Constituents - in vitro Studies. PMID- 17345513 TI - Immunomodulation of human complement system by plant extracts and isolated pure compounds. PMID- 17345514 TI - Immunological Investigations of Naphthaquinone-containing Plant Extracts, Isolated Quinones and other Cytostatic Compounds in Cellular Immunosystems. PMID- 17345515 TI - Inhibition of Different Gonadotropins by Plant Extracts and Phenolic Plant Constituents - in vitro Studies. PMID- 17345516 TI - Investigations on the antigonadotropic activity of caffeic Acid esters. PMID- 17345517 TI - Fertility Regulation through Indigenous Plants and their Mode of Action. PMID- 17345519 TI - Screening of thymelaeaceae species for irritant, cocarcinogenic and antineoplastic activity. PMID- 17345518 TI - Ethnopharmacological Study of Azadirachta indica. A Conceptual Evaluation. PMID- 17345520 TI - Investigation of Medicinal Plants for their Antiproliferative Activities Against a Human Tumour Cell Line. PMID- 17345521 TI - Preparation of 14C-Spiro Ethers by Chamomile and their Use by an Investigation of Absorption. PMID- 17345522 TI - Antitumor Activity of Triterpenes in Inonotus obliquus. PMID- 17345523 TI - Purification and Biological Characterization of Antiviral Substances from Thuja occidentalis. PMID- 17345524 TI - Antitumor Activity of the Hot Water Extract of Lobelia chinensis. PMID- 17345525 TI - Antimicrobial Activity of Benzylisoquinoline Alkaloids. II. Relation Between Chemical Composition and Antimicrobial Activity. PMID- 17345526 TI - Mechanism of antimicrobial activity of essential oils. PMID- 17345527 TI - Further Saponins from Phytolacca dodecandra: their Molluscicidal and Spermicidal Properties. PMID- 17345528 TI - Volatile oil of Pernettya mucronata and its Antischistosomal Activity. PMID- 17345529 TI - Insecticidal chromenes from desert sunflowers. PMID- 17345530 TI - Insecticidal Activity of Monadenium lugardae Latex. PMID- 17345531 TI - [Non-infective inflammations of the vertebral spine]. AB - Non-infective inflammations of the vertebral spine can be caused by seronegative spondylarthropathies or rheumatoid arthritis, respectively. Seronegative spondylarthropathies include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel diseases and undifferentiated arthritis. This review discusses etiology and pathogenesis, epidemiology, clinical features, diagnosis and differential diagnoses of these chronic inflammatory diseases with a special focus on vertebral involvement. PMID- 17345532 TI - [Time interval between accident and operation in relation to long-term outcome]. PMID- 17345533 TI - [Global symposium on motion preservation technology in Berlin]. PMID- 17345534 TI - [47th Congress of the German Society of Hand Surgery in Heidelberg]. PMID- 17345536 TI - [Guidelines in orthopedics and trauma surgery]. PMID- 17345537 TI - [Support project of the International Charite Organization in Vietnam]. PMID- 17345540 TI - [Stress on the knee joint by knee bending as prearthrosis]. AB - AIM: Purpose of our study was to prove from the orthopaedic point of view whether or not osteoarthrosis of the knee joint may be regarded as an occupational disease under certain physical loads. METHOD: A review and meta-analysis of occupational medicine literature was undertaken, which was reported as a scientific background for the planned occupational disease study "gonarthrose" in Germany. RESULTS: There exist only four relevant epidemiological studies, showing a correlation between osteoarthrosis of the knee joint and knee flexion under conditions of physiological stress. None of them proves that knee flexion causes osteoarthrosis. It may be only concluded with some restriction that occupations involving extensive kneeling or squatting influence the progress and course of osteoarthrosis of the knee--together with other pathogenetic and aetiological factors. CONCLUSION: It cannot be concluded from occupational studies that kneeling and squatting or similar physical strains during work cause osteoarthrosis of the tibio-femural or patello-femoral joint. On the basis of methodical epidemiological and biomechanical considerations a causative correlation as described before cannot be expected. Nevertheless, in the occupational literature one can find some circumstantial evidence which may show whether mechanical functional stress influences the course of knee arthropathy (such as early patella osteophytes, osteoarthrosis of ankle joints) or not (early tibio-femural osteoarthrosis, lack of osteophytes in the elderly). PMID- 17345541 TI - [The prognostic influence of primary tumour and region of the affected spinal segment in 217 surgical patients with spinal metastases of different entities]. AB - AIM: A retrospective study to evaluate the prognostic influence of the primary tumour and the anatomic level of spinal metastases was carried out. MATERIAL AND METHODS: Between January 1984 and May 2005, 217 patients were surgically treated because of spinal metastases. The prognostic influence for the survival was analysed for the entity of the primary tumour and the localisation of the spinal metastases. RESULTS: The median survival of the study group was 8.0 months (range: 0-191.5 months). Mamma carcinoma was the most frequent primary tumour with 62 cases (28.6 %). The spinal level of the metastases did not influence the postoperative survival (p = 0.9058). The entity of the primary tumour showed a significant influence for the postoperative survival (p < 0.0001). CONCLUSION: In spinal metastases, the entity of the primary tumour was of prognostic value; the localisation of the spinal metastases at different spinal levels did not influence the postoperative survival. Therefore, the evaluation of the primary tumour is mandatory for an estimation of the expected survival. PMID- 17345542 TI - [A prospective two-year follow-up of thoracic and lumbar osteolytic vertebral fractures caused by multiple myeloma treated with balloon kyphoplasty]. AB - PURPOSE: Balloon kyphoplasty is a minimally invasive procedure for the stabilization of osteoporotic and osteolytic vertebral fractures. The purpose of this prospective study was to evaluate this operative procedure in the treatment of osteolytic vertebral fractures with regard to the reduction of pain and functional improvement of the patients and further to evaluate the restoration of vertebral height postoperatively. MATERIALS AND METHODS: In this study 26 patients (21 male, 5 female) with osteolytic vertebral fractures were treated with balloon kyphoplasty. In total, 59 vertebral fractures were treated with balloon kyphoplasty. Preoperatively conventional radiographs in lateral and a. p. views, CT and/or MRI were preformed. Pre- and postoperatively the clinical parameters using VAS (visual analogue scale) and the Oswestry score were evaluated. Radiographic scans were performed pre- and postoperatively and after 3, 6, 12 and 24 months. The vertebral height and endplate angles were measured. RESULTS: The median pain scores (VAS) decreased from pre- to post-treatment significantly (p < 0.05) as also did the Oswestry score (p < 0.05). Balloon kyphoplasty led to a significant and sustained reduction of pain resulting in a significant functional improvement for the patients. A significant restoration of vertebral height and reduction of the kyphotic angle could be achieved with the balloon technique (p < 0.05). Furthermore, the minimal-invasive procedure was able to stabilize the spine also over a longer period of 24 months. A radiation therapy and/or chemotherapy could be performed without loss of time. CONCLUSION: In the treatment of osteolytic vertebral fractures balloon kyphoplasty led to a quick and sustained reduction of pain and as well as a functional improvement for the patients. A restoration of the vertebral height and reduction of the kyphotic angle was especially attributable to the balloon technique. The balloon kyphoplasty was able to stabilize the fractured vertebrae in the long-term and was able to prevent an increase of kyphotic deformity. Balloon kyphoplasty is an outstanding alternative in comparison to the established therapeutic concepts in the treatment of osteolytic vertebral fractures. PMID- 17345543 TI - [PLIF and ALIF for the degenerative spondylolisthesis of the lumbar spine]. AB - AIM: The aim of this study is to compare the course of disease of patients with a degenerative instability of the lumbar spine after PLIF or ALIF. MATERIALS AND METHODS: Between October 1995 and January 2000 115 patients underwent a ventral or dorsal spondylodesis due to a degenerative instability in the Department of Neurosurgery of the Unfallkrankenhaus Berlin Hospital and in the Department of Neurosurgery of the Friedrichshain Hospital in Berlin. At an average of 25 (13 64) months after surgery these patients were followed up in a clinical examination and a questionnaire concerning their sense of pain and quality of life. RESULTS: Significant improvement after surgery has been shown in both groups. The recovery rate was 52 % which is a beneficial result. The fusion rate was 91 %. The postoperative sense of pain declined with regard to the visual pain scale. The intake of analgetics decreased in a quantitative as well as in a qualitative way. With 94 % the acceptance of the operation was comparatively high. The number of complications was low in comparison with the literature (4 %). There was no operative lethality. CONCLUSIONS: With regard to the indications and contraindications the PLIF as well as the ALIF is accepted unquestioningly as an up-to-date method. PMID- 17345544 TI - [Epidural varicosis as a rare cause of acute radiculopathy with complete foot paresis--case report and literature review]. AB - INTRODUCTION: Lumbar epidural varicosis presenting with radiculopathy is a seldom anticipated condition. An uncommon case of symptomatic enlargement of epidural veins mimicking lumbar disc herniation led us to perform a literature review to elucidate aetiopathological and diagnostic considerations as well as treatment options of this intraspinal pathology. METHODS: The case of a 40-year-old woman with acute sciatia accompanied by a complete paresis of foot elevation and extension caused by enlarged epidural veins is described. A literature survey (Medline 1960-2005) was conducted to uncover further cases of symptomatic epidural varicosis. RESULTS: The literature review revealed only 75 published cases of symptomatic epidural varices which is generally judged as a rare cause of radiculopathy. Different models for the origin of enlarged epidural veins have been proposed. Enlargement may occur primary or secondary to a herniated disc or compressive lesions in the spinal cord. In some cases obstruction or occlusion of the inferior vena cava due to pregnancy or deep vein thrombosis are suspected to increase the pressure of the epidural venous plexi via collateral pathways. MRI has been reported to be of high value in demonstrating the dilated epidural vein, but the findings might be misinterpreted as herniated nucleus pulposus material. Coagulative ablation and/or excision of enlarged epidural veins is recommended and produces good long-term results in cases without extraspinal vessel pathology. CONCLUSION: Enlargement of epidural veins with compression of lumbar nerve roots can mimic the clinical signs of disc herniation or spinal stenosis, even when accompanied by neurological disorders. Although rare, lumbar epidural varicosis should be appreciated as a possible cause of radiculopathy and diagnosed before surgery. Apart from intraspinal abnormalities causing dilatation of epidural veins, stenosis or occlusion of the extraspinal venous drainage system should be considered. PMID- 17345545 TI - [Total hip replacement in the G-DRG-system]. AB - AIM: Due to the continuing increase in life expectancy, the ageing process of the German population in general and the high demands placed on activity levels and quality of life today, the demand for primary and secondary joint replacement surgery continues to increase. To distribute the economic and medical resources properly, while still making technical and surgical innovations available to a broad public, hospitals must be able to adequately finance these procedures with the help of the proper diagnosis related groups. METHOD: The development of the German DRG-system over the past years, as well as the new calculation for the year 2006 are to be reviewed and analysed in this article with this in mind. RESULTS: An improvement in the degree of differentiation between the individual procedures can be documented. CONCLUSION: Whether or not these changes will ensure the long-term financial survival of the German health care system will remain to be seen. PMID- 17345546 TI - [Total hip replacement in high total hip dislocation by performing a Z-shaped shortening osteotomy]. AB - AIM: Total hip arthroplasty for severe chronic proximal femoral migration, most commonly seen in congenital dislocation of the hip, has been associated with high rates of complications. Placement of the acetabular component in the true acetabulum has yielded the most durable results, but leads to significant limb lengthening. In this paper six cases of a total hip arthroplasty combined with a Z-shaped osteotomy of the proximal femur are described. METHOD: All patients presented with a complete congenital dislocation of the hip. In all procedures the acetabular component was placed in the true acetabulum and the proximal femur was shortened according to a preoperative drawing in a Z-shaped manner. RESULTS: The clinical and radiological results of the patient collective are presented in this study, the mean follow-up period was 60 months. At the last follow-up no nerve palsy, osteotomy pseudarthrosis or dislocation were detected objectively. CONCLUSION: The performed procedure seems to be a viable technique in the treatment of coxarthritis in high total hip dislocation. PMID- 17345547 TI - [Measurement of ground reaction forces after total hip arthroplasty using different surgical approaches]. AB - AIM: Benefits of less damage of soft tissues and muscles in minimally invasive hip replacement lead to expectations of better results in gait rehabilitation. The aim of the study is to evaluate post-operative walking ability in terms of different surgical approaches. METHOD: 16 patients underwent a minimally invasive total hip replacement (MIS group) and 16 other patients got a THA using a transgluteal approach (standard group). Differences in functional indices of ground reaction forces and symmetry indices were measured one day pre-operatively as well as 8, 14 and 28 weeks post-operatively. The results were compared between the surgical approaches and to an age-matched healthy control group. RESULTS: There are significantly reduced pain symptoms and a higher functional ability in both surgical groups 8 weeks post-operatively. There are no differences in gait parameters between the surgical groups after 28 weeks. Trends in gait velocity, temporal parameters and in functional indices of ground reaction forces show advantages for the minimally invasive group 8 and 14 weeks post-operatively. Patients do not reach the age-matched control group. CONCLUSION: Obviously the immediate post-operative advantages of minimally invasive hip replacement provide better chances for gait rehabilitation compared to the transgluteal approach. Due to the complexity of the problem clinical and gait analysis studies should be linked more closely. PMID- 17345548 TI - [Photoelastic stress analysis of human femurs before and after implantation of different models of femur neck prostheses]. AB - AIM: The aim of this study was the detection of areas at risk at the proximal femur after implantation of different femur neck prostheses using the photoelastic stress analysis. METHODS: Twelve pairs of human femurs were used as examination material. The analysis of the stress pattern was done with a stepwise increasing load up to the quadruple of body weight before and after implantation of three models of femur neck prostheses which were implanted cementless. The "CUT" and "Cigar" models are coated with a tripod structure. The "Cigar" model has a lateral thrust plate. The lateral end of the "CUT" model is curved and this end is attached to the lateral corticalis. The third model, the "rip prosthesis" has two layers for rotational stability. Subsequently, the micromotions of the implanted prosthesis in the femural neck were examined with alternating weight loads (1000 +/- 700 N). RESULTS: The Cigar prosthesis showed the most changes of stress distribution because of the lateral thrust plate with concentration of isochromatic lines to the lateral boring. In the region of the oseotomy an increase of strain up 1440 microm/m could be detected for the Cigar and up to 1000 microm/m for the rib prosthesis. The stress pattern after implantation of the CUT prosthesis remained very similar apart from a slight increase of stress values (720 microm/m). Only for the Cigar prostheses were the measured micromotions below the critical value for a possible osteointegration with a mean value of 134 microm/m. CONCLUSION: The stress pattern after implantation of the CUT prosthesis remained most similar to the preinterventional stress distribution. Because of this, it is to be expected that the osseous modification would stay at a low level. The question of osteointegration can only be answered in long-term in-vivo studies. PMID- 17345549 TI - [Bilateral fracture of the femoral neck following transient osteoporosis in pregnancy]. AB - During pregnancy changes of the bone metabolism can occur. Femoral neck fractures are known as a very rare consequence of transient osteoporosis in pregnancy. In a case report we present the clinical, radiological and histological features of a bilateral fracture of the femoral neck. A 29-year-old woman presented with pain in the right hip, which occurred in the 34 (th) week of pregnancy. The symptoms were initially interpreted as a sacroiliac joint affection and consequently a conservative treatment was initiated. Five days after a Caesarean section a dislocated fracture of the femoral neck was diagnosed on the left side. On the contralateral side the fracture was not dislocated. For therapy this patient underwent a total hip replacement on the left hand side and an internal fixation on the other side. Especially during pregnancy changes of the bone are diagnosed late due to the side effects of radiation. This case report indicates that MR imaging and other non-ionising techniques should be considered if such symptoms persist in spite of therapy. PMID- 17345550 TI - [Predictive factors of perioperative morbidity in revision total hip arthroplasty]. AB - AIM: The awareness and prevention of perioperative morbidity are essential in revision total hip arthroplasty [THA]. Therefore, it was the purpose of this study to assess the rate of perioperative complications following revision THA in order to evaluate the impact of patient- and procedure-related variables. METHODS: 169 consecutive patients with a mean age of 71.7 years suffering from aseptic loosening of their THA were included in this retrospective study. Multivariate logistic regression models with estimation of the odds ratio [OR] and 95% confidence interval [CI] served to analyze the influence of operation duration, gender, revision status, ASA classification, and type of fixation of the primary implant on the perioperative morbidity. RESULTS: 68.6% of the cases were primary revisions, and 31.4% secondary or multiple revisions. 49.7% of the operations involved exchange of the complete implant whereas 39.1% comprised exchange of the cup and 11.2% exchange of the stem only. Mean operation duration was 130 minutes [min] (range: 40-260 min), and mean intraoperative blood loss was 2.6 L (0.5 to 12 L). The rate of intraoperative complications was 10.1 % with a 6.5 % fracture rate. Postoperatively the complication rate was 25.4% with an 8.3% rate of luxations. 11.8% of the patients had revision within the first three weeks after surgery. Regression models showed the significant impact of revision status (primary vs. secondary or multiple: OR 2.90, 95% CI 1.42-5.92) and operation duration (per min starting from the mean operation time: OR 1.01, 95% CI 1.00-1.02) on the resulting complication rate. Analysis of the perioperative complication rate following primary revisions revealed a significant difference (p = 0.03) between patients with cemented (15/36, 41.7%) and non-cemented (8/45, 17.8%) implants. CONCLUSIONS: Revision status with a three-fold increase in patients with multiple revisions as well as operation duration with a 1 % increase per min starting from the mean operation time significantly influence the perioperative morbidity. Patients with a first revision, furthermore, seem to be at greater risk for an adverse event perioperatively if their implant is fully cemented. These findings should be taken into account prior to initiating surgery. PMID- 17345551 TI - [Knowledge transfer and student's satisfaction in orthopaedics--a survey of 476 students]. AB - AIM: The aim of the current study was to find out about the student's growth of knowledge and satisfaction in orthopaedics. We performed a survey among 476 students of one faculty. METHOD: We performed an anonymous survey in which the students had to answer a questionnaire which consisted of items according to knowledge in orthopaedics, subjective satisfaction and according to the difficulty of the asked questions. RESULTS: 74% of students disliked the so called "hammerexam." 56% believe that the transfer of knowledge is good in lectures and bedside teaching courses. 20% prefer to cancel the "hammerexam," 30% would prefer to spend more time for important sections such as surgery and internal medicine and 20% would prefer it if the practical aspects of medicine were placed in the foreground. During the third and fourth semesters, the increase of knowledge is at its highest but is reduced later. 4% of all asked students are planning to become orthopaedic surgeons. CONCLUSION: Our study demonstrates that good knowledge transfer within the modified lectures and bedside teaching lessons is achieved. Student satisfaction is high. Only very few students are critical about their current situation. PMID- 17345552 TI - [Differential behaviour of human adult arthrotic chondrocytes under 2D- and 3D cultivation set-ups in a collagen I gel]. AB - AIM: The aim of this study was to assess the influence of culture conditions on the differentiation of human chondrocytes expanded in monolayer (2 D) or a three dimensional (3 D) biodegradable collagen type I matrix, with regard to chondrocyte-specific markers. METHOD: Human arthrotic chondrocytes were taken from nine adult donors (average age 72.1 years) undergoing knee replacement. The isolated cell suspensions were split and cultivated either in a 3-dimensional collagen gel (3 D) or in a monolayer (2 D). The amounts of mRNA for collagen I and II, aggrecan and melanoma inhibitory activity (MIA) were quantified by means of real-time PCR at different times. RESULTS: The 2 D-passaged cells showed a significant increase of collagen I between P 00 and P 01 (p = 0.009), whereas the expression of collagen II decreased significantly (p = 0.022). There was no significant change for collagen I in 3 D-cultivation, whereas the collagen II expression decreased significantly after 2 to 4 weeks (p = 0.001). CONCLUSION: Human adult chondrocytes obtained from elderly patients showed a decreased expression of collagen II with increased passaging in the monolayer (2 D). The decrease was delayed in 3 D-cultivation. We thus question the assumption that the dedifferentiation of chondrocytes can be prevented or reversed by 3 D cultivation. Based on our results, we recommend the use of freshly isolated and therefore sparsely dedifferentiated chondrocytes for transplantation. PMID- 17345553 TI - [Clinical update on Hunter syndrome (MPS II). Introduction]. PMID- 17345554 TI - [Follow-up of patients with Hunter syndrome: the Hunter Outcome Survey (HOS) registry]. AB - INTRODUCTION: Hunter syndrome, or mucopolysaccharidosis type II, is an inherited disease linked to the X chromosome that is caused by a deficit of the enzyme iduronate-2-sulfatase and its main symptoms affect the bones, neurological system and the viscera. In order to further our knowledge of its natural history, a registry containing data about patients' clinical histories was compiled. The purpose of this review is to describe how the registry works and to present the initial data concerning Spanish patients with Hunter syndrome included in it. DEVELOPMENT: The Hunter Outcome Survey (HOS) registry is a multi-centre, world wide, observational, long-term follow-up study that is open to all patients diagnosed with the disease. The registry includes clinical data and information from the complementary examinations that are commonly performed as usual practice while attending these patients. Its main aims are to describe the population of patients with the disease, to further our knowledge of its natural history, to keep a check on the safety and effectiveness of enzyme replacement therapy in patients who are candidates for such treatment and to create a database that makes it possible to draw up a set of guidelines for clinical practice. CONCLUSIONS: Specific registries of low-prevalence diseases, such as the HOS registry for patients with Hunter syndrome, are important to improve the follow up of patients and to determine the impact of new treatments. The Spanish HOS registry is an important step forward in furthering our knowledge of the current situation of the patients registered throughout the country. PMID- 17345555 TI - [Clinical aspects of mucopolysaccharidosis type II]. AB - AIM: To review the clinical and diagnostic aspects of mucopolysaccharidosis type II (Hunter syndrome). DEVELOPMENT: The different phenotypes are described and the multisystem clinical symptoms are considered, with special emphasis on skeletal deformities and cardiorespiratory and neurological complications. CONCLUSIONS: Paediatricians and certain specialists (in neurology, ORL, rheumatology and cardiology) must be aware of the need to increase the clinical suspicion of this condition, which can nowadays be treated using enzyme replacement therapy. PMID- 17345556 TI - [Clinical study of enzyme replacement therapy with idursulfase]. AB - INTRODUCTION: Important advances have been made in enzyme replacement therapy in the treatment of lysosomal diseases over the last two decades. Here we review the initial ERT trial using idursulfase in Hunter syndrome (mucopolysaccharidosis type II) and we also examine relevant aspects of the use of this enzyme. DEVELOPMENT: A preclinical trial in a knockout mouse showed a decrease in glycosaminoglycans, both in urine and in tissues, following treatment with idursulfase. In a randomised, double-blind, placebo-controlled clinical study in phase I/II conducted in 12 patients with Hunter syndrome, treatment with idursulfase displayed a good safety profile and also a decrease in the excretion of glycosaminoglycans and cases of visceromegaly. The 12 patients continued the study in an open manner for two years and favourable outcomes were also obtained. A recent randomised, double-blind, placebo-controlled, multi-centre and multinational study in phase II/III conducted with 96 patients with Hunter syndrome over one year showed that the administration of 0.5 mg/kg doses of idursulfase significantly improved the final 'combined' score, which was the sum of the changes in the percentage of predicted forced vital capacity and in the 6 minute walk test, in comparison to the response obtained with a placebo. This result was the same for the weekly treatment group (p = 0.0049) and the fortnightly group (p = 0.0416). Many of the secondary effectiveness parameters also improved significantly, especially in the weekly treatment group. Treatment with idursulfase was well tolerated, with side effects that were, generally speaking, mild or moderate. IgG antibodies were detected in up to 46.9% of the patients treated in the two groups, but no apparent relation with the side effects or the clinical response was observed. CONCLUSIONS: Treatment with 0.5 mg/kg of idursulfase in weekly intravenous infusions is usually well tolerated and seems to improve the somatic symptoms in patients with mucopolysaccharidosis type II. PMID- 17345557 TI - Exploring the economic impact of breast cancers during the 18 months following diagnosis. AB - The economic impact on individuals with breast cancer is not well understood. We sought to identify and describe the direct and indirect economic losses to breast cancer survivors in Australia. A longitudinal, population-based study of 287 women was used to explore economic outcomes (costs and lost income) for women with breast cancer 0-18 months post-diagnosis. Survey methods collected data on out-of-pocket costs, care-giving support, paid and unpaid work reductions, and perceptions from participants on these financial impacts. Bootstrapping was used to estimate 95% confidence intervals around means. Data were sub-grouped by cost type, age category and disease severity. Lost income, health service expenditures and lost unpaid work were the greatest sources of economic burden. Women with positive lymph nodes reported significantly higher costs than those with negative lymph nodes (US$6674 versus US$3533, p<0.001), and younger women (< or =50 years) with positive lymph nodes experienced costs 80% greater than older women (US$8880 versus US$4937, p<0.001). Economic costs related to breast cancer may continue to affect women 18 months post-diagnosis. Economic research adds an important dimension for understanding the impact of breast cancer, and findings may be used to help improve supportive care services for women and families confronted by this disease. PMID- 17345558 TI - Monitoring and blunting in palliative and curative radiotherapy consultations. AB - OBJECTIVE: The present research paper investigates how cancer patients' monitoring and blunting coping styles are reflected in their communications during their initial radiotherapy consultations and in their evaluations of the consultation. Additionally, it is explored how a patient's disease status (curative versus palliative) influences the effects of his or her cognitive styles. METHODS: The study included 116 oncology patients receiving treatment from eight radiation oncologists. For 56 patients treatment intent was palliative and for the remaining 60 curative. The patients' communicative behaviors were assessed using the Roter Interaction Analysis System (RIAS). Within three days the patients completed a monitoring and blunting inventory and after another six weeks they evaluated the treatment decision and treatment information by postal questionnaire. RESULTS: Monitoring was positively and blunting negatively related to the patient's expression of questions, emotions and decision-making issues. After six weeks 'high monitors' as opposed to 'low monitors' reported having more doubts about the treatment decision and being less satisfied with the information received while 'high blunters' expressed fewer doubts and more satisfaction than 'low blunters' did. Significant associations were all attributable to the palliative treatment group. CONCLUSION: Cancer patients' communicative behaviors vis-a-vis their oncologist hinge on their cognitive styles and an unfavorable disease status enhances the effects. PMID- 17345559 TI - The correlation between coping strategies, doctor-patient/spouse relationships and psychological distress among women cancer patients and their spouses. AB - OBJECTIVES: The objectives of the study were (1) to assess similarities and differences between women cancer patients and their spouses in terms of coping strategies, psychological distress and doctor-patient/spouse relationships; and (2) to investigate the impact of formal social support, namely the doctor-patient relationship and coping strategies, on patients' and spouses' psychological distress. METHOD: Fifty-seven women with cancer, and their spouses, completed questionnaires that measured distress (BSI), coping strategies (PF, EF) and doctor-patient relationships (Pat, Md). RESULTS: Patient distress was greater than that of spouses. Patients used more strategies involving problem-focused coping than spouses. A positive relationship was found between patients and spouses in terms of psychological distress, paternalism and emotion-focused strategies. Emotion-focused strategies were found to impact patient psychological distress, as indicated in a hierarchical regression model. CONCLUSION: The paternalism relationship model is an important factor in patient psychological distress but not in spousal psychological distress. PMID- 17345560 TI - Enantioselective and diastereoselective Michael addition of ketone/aldehyde to trans-nitroolefins catalyzed by a novel chiral pyrrolidine-thiourea. AB - The direct Michael addition reaction of cyclohexanone/aliphatic aldehydes with nitroolefins, catalyzed by a novel chiral pyrrolidine-thiourea catalyst 1a, is described. The desired 1,4-adducts were obtained in moderate yields with enantioselectivities up to 99% ee and dr up to 99:1 of the syn product. PMID- 17345561 TI - Stereoselective degradation of fungicide benalaxyl in soils and cucumber plants. AB - The enantioselective degradation of benalaxyl has been investigated to elucidate its behavior in several agricultural soils and plants (cucumber). Racemic benalaxyl was fortified into five types of agricultural soils and sprayed leaves of cucumber plants, respectively. The degradation kinetics and the enantiomer fraction (EF) were determined by normal-phase high-performance liquid chromatography (HPLC) with diode array detection (DAD) on the chiral column filled cellulose-tri-(3,5-dimethylphenylcarbamate)-based chiral stationary phase (CDMPC-CSP). The process of the degradation of benalaxyl enantiomers followed pseudo-first-order kinetics in cucumber plant. However, the dissipation phases of benalaxyl enantiomers in soils were biphasic ("slow-fast-slow" process). It has been shown that the degradation of benalaxyl was stereoselective. The results indicated that the (+)-S-benalaxyl showed a faster degradation in plants, while the (-)-R-benalaxyl showed a faster degradation in Soils 3, 4, and 5. No stereoselective degradation was observed in other soils. PMID- 17345562 TI - Effect of surface coverage of gold(111) electrode with cysteine on the chiral discrimination of DOPA. AB - The enantioselectivity imparted to a gold electrode by modifying its surface with a self-assembled monolayer (SAM) of cysteine (Cys) was investigated for the electrochemical redox reaction of 3,4-dihydroxyphenylalanine (DOPA). A cyclic voltammetric study of the redox reaction revealed that the enantioselectivity was determined by the surface coverage of the gold electrode with Cys molecules. The electrode modified with approximately 1.8 x 10(14) Cys molecules cm(-2) exhibited enantioselectivity in the voltammogram for the oxidation and reduction of DOPA, while the voltammograms obtained by the electrodes with either more or less surface coverages did not exhibit significant enantioselectivity. It is suggested that the accessibility of DOPA to that area of the gold surface which is not blocked by Cys molecules at an optimum surface coverage, is required for the enantioselective redox reaction of DOPA to proceed. PMID- 17345563 TI - Chirality as a tool in nucleic acid recognition: principles and relevance in biotechnology and in medicinal chemistry. AB - The understanding of the interaction of chiral species with DNA or RNA is very important for the development of new tools in biology and of new drugs. Several cases in which chirality is a crucial point in determining the DNA binding mode are reviewed and discussed, with the aim of illustrating how chirality can be considered as a tool for improving the understanding of mechanisms and the effectiveness of nucleic acid recognition. The review is divided into two parts: the former describes examples of chiral species interacting with DNA: intercalators, metal complexes, and groove binders; the latter part is dedicated to chirality in DNA analogs, with discussion of phosphate stereochemistry and chirality of ribose substitutes, in particular of peptide nucleic acids (PNAs) for which a number of works have been published recently dealing with the effect of chirality in DNA recognition. The discussion is intended to show how enantiomeric recognition originates at the molecular level, by exploiting the enormous progresses recently achieved in the field of structural characterization of complexes formed by nucleic acid with their ligands by crystallographic and spectroscopic methods. Examples of application of the DNA binding molecules described and the role of chirality in DNA recognition relevant for biotechnology or medicinal chemistry are reported. PMID- 17345564 TI - Application of mixtures of tartaric acid derivatives in resolution via supercritical fluid extraction. AB - Racemic N-methylamphetamine (rac-MA) was resolved with 2R,3R-tartaric acid (TA) and its derivatives (O,O'-dibenzoyl-(2R,3R)-tartaric acid monohydrate (DBTA) and O,O'-di-p-toluoyl-(2R,3R)-tartaric acid (DPTTA)), individually and using them in different combinations. After partial diastereomeric salt formation, the free enantiomers were extracted by supercritical fluid extraction using carbon dioxide as solvent. DBTA and DPTTA are efficient resolving agents for rac-MA, the best chiral separation being obtained at a molar ratio of 0.25 resolving agent to racemic compound for both resolving agents (ee(E) = 82.5% and ee(E) = 57.9%, respectively). Compared with the two other acids, TA is practically unsuitable for enantiomer separation (ee(E) < 5%). Applying a mixture of one individually active and one ineffective acid in half the equivalent molar ratio, when the acids are in 1:1 ratio in the mixture, the resolution efficiency values obtained exceeded those obtained by using the components individually. Decreasing the molar ratio of resolving agent mixture to 0.25, at which the individual resolving agents give the best chiral separation, the obtained resolution efficiency values did not differ significantly from those expected. The outcome of the resolution process depended only on the amount of the individually active resolving agents in the mixture. PMID- 17345565 TI - Retraction. "Protective Effects of Isothiocyanates towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay". PMID- 17345567 TI - 'Mycotoxin identification in moldy dwellings'. PMID- 17345568 TI - Early stopping designs based on progression-free survival at an early time point in the initial cohort. AB - We introduce a new study design in which patients are evaluated early in their treatment for disease progression. Our design is appropriate when lack of progression, both early and late, is the criterion for treatment success. An initial cohort of n(1) patients is followed until the last one has been evaluated. If enough of these patients are progression free (PF) at an early time point, t(1) after arrival, a second cohort is recruited until n(2) total patients are evaluable for PF survival at the final time t(2). Otherwise, the trial is terminated for futility both early in time and with a minimal number of patients. Patients in the initial cohort who are PF at t(1) continue on study and are again evaluated at t(2). The design permits early stopping for rapid progression of disease, an indication of futility both for cytotoxic and newer non-cytotoxic targeted therapies. The design tests the composite hypothesis of a probability p(1) of being PF at t(1) and p(2) of being PF at t(2) given PF at t(1). Power and type I error are maintained at design point levels over a wide range of parameters p(1) and p(2). No distributional assumptions are needed other than the binomial, so the design provides rigorous power analysis for this type of study. Tables of optimal designs are supplied for a broad range of requirements. PMID- 17345569 TI - High-performance liquid chromatography/electrospray ionization tandem mass spectrometry of hydroxylated uroporphyrin and urochlorin derivatives formed by photochemical oxidation of uroporphyrinogen I. AB - Hydroxylated uroporphyrin I and urochlorin I derivatives formed by photochemical oxidation of uroporphyrinogen I were separated by high-performance liquid chromatography and fully characterized by electrospray ionization tandem mass spectrometry. The porphyrins and chlorins were identified by analysis of their product ion spectra with each hydroxylated derivative giving a characteristic collision-induced dissociation fragmentation pattern. The porphyrins and chlorins characterized were meso-hydroxyuroporphyrin I, alpha-hydroxypropionic acid uroporphyrin I, beta-hydroxypropionic acid uroporphyrin I, hydroxyacetic acid uroporphyrin I, trans-7-hydroxy-8-spirolactoneurochlorin I, cis-7-hydroxy-8 spirolactoneurochlorin I and trans- and cis-7,8-dihydroxyurochlorins I. PMID- 17345570 TI - Methods for the characterization of Jet Propellent-8: vapor and aerosol. AB - Jet Propellant-8 (JP-8) has been responsible for the majority of reported chemical exposures by the US Department of Defense. Concerns related to human exposure to JP-8 are relatively new; therefore, there is a lack of literature data. Additionally, health effects related to the composition of the exposure have only recently been considered. Two major questions exist: (1) what is the compositional difference between the aerosol and vapor portions of JP-8 under controlled conditions and (2) what is the most representative method to sample JP 8 aerosol and vapor? Thirty-seven standards, representing more than 40% of the mass of JP-8, were used for characterization of the neat fuel, vapor and aerosol portions. JP-8 vapor samples at a concentration of 1600 mg/m(3) were prepared in Tedlar bags. A portion of the vapor samples was adsorbed on charcoal, Tenax and custom mixed phase sorbents. These samples were then extracted using organic solvent and analyzed using gas chromatography/mass spectrometry. The vapor samples extracted from the sorbent tubes were directly compared with a vapor bag. The samples collected using Tenax sorbent tubes were found to be most representative of the composition of the vapor bags. In another set of experiments, aerosolized JP-8 was generated using a collision nebulizer. Aerosol samples were collected and the chemical composition was characterized. The entire aerosol distribution was collected on a glass filter, extracted into solvent, and analyzed by GC-MS. Finally, the composition of the vapor and aerosol was compared. The vapor was found to represent the lower molecular weight components of JP-8, while the aerosol was composed of higher molecular weight components. Therefore, the vapor and aerosol should be treated as two discrete forms of exposure to JP-8. PMID- 17345571 TI - Theoretical study of the role of solvent H2O in neopentyl and pinacol rearrangements. AB - The neopentyl and the pinacol rearrangements as examples of Wagner-Meerwein rearrangements were investigated by the use of DFT calculations. As the first reaction, a model of neopentyl chloride (1b) and (H2O)12 was employed. In the reaction, the patterns of C--Cl scission, methyl migration, and C--OH formation were analyzed. The calculations have shown that the 2-methyl-2-butanol (6) is formed in two steps with the transient intermediate, neopentyl alcohol (3). The first step is the nucleophilic substitution reaction and is the rate-determining one. The second step is the dual migration of methyl and OH2 groups. The primary and tertiary carbocations were calculated to be absent in the neopentyl rearrangement starting from the hydrolysis. As the second reaction, the pinacol rearrangement of two substrates 2,3-dimethyl-2,3-butanediol (7) and 2,3-diphenyl 2,3-butanediol (12) was investigated. Acidic aqueous solvent was modeled by H3O+ and 12H2O. The reaction paths were promoted by a hydrogen-bond circuit of H3O+(H2O)2 and were determined as completely concerted processes. Protonated species and carbocations as intermediates also do not intervene during the pinacol rearrangement. Active functions of proton relays along the hydrogen bonds in the two rearrangements were demonstrated. PMID- 17345572 TI - Quantitative LC/MS/MS method and pharmacokinetic studies of columbin, an anti inflammation furanoditerpen isolated from Radix Tinosporae. AB - Columbin is an important component isolated from Radix Tinosporae. It has been demonstrated to possess many pharmacological activities, including anti inflammation, antitumor and inhibition of enzyme activity in vivo. The purpose of the present study was to examine in vivo pharmacokinetics and bioavailability of columbin in rats using a high-performance liquid chromatography coupled with tandem mass spectrometry quantitative detection method. The columbin was extracted from rat plasma samples by methyl tert-butyl ether, evaporated and reconstituted in 100 microL methanol prior to analysis. The separation was performed using a Luna reversed-phase analytical column (5 microm, 100 x 2.0 mm) and an SB-C18 guard column (5 microm, 20 x 4.0 mm). The mobile phase was a mixture of methanol and water containing 25 mmoL/L NH(4)Ac (80:20, v/v). The method was validated within the concentration range of 5-5000 ng/mL, and the calibration curves were linear with correlation coefficients (r) >0.999. It was further applied to assess pharmacokinetics and oral bioavailability of columbin after i.v. and oral administration to rats. The oral bioavailability of columbin was only 3.18%, which indicated that columbin had poor absorption or underwent extensive first-pass metabolism. PMID- 17345573 TI - Evaluation of GSH adducts of adrenaline in biological samples. AB - The sustained high release of catecholamines to circulation is a deleterious condition that may induce toxicity, which seems to be partially related to the products formed by oxidation of catecholamines that can be further conjugated with glutathione (GSH). The aim of the present study was to develop a method for the determination of GSH adducts of adrenaline in biological samples. Two position isomers of the glutathion-S-yl-adrenaline were synthesized and characterized by HPLC using diode array, coulometric and mass detectors. A method for the extraction of these adducts from human plasma was also developed, based on adsorption to activated alumina, which showed adequate recoveries and proved to be crucial in removing interferences from plasma. The selectivity, precision and linearity of the method were all within the accepted values for these parameters. Furthermore, the sensitivity of this method allows the detection of adduct amounts that are within the range of the expected concentrations for these adducts under certain pathophysiological conditions and/or drug treatments. In conclusion, the development of this method allows the direct analysis of GSH adducts of adrenaline in human plasma, providing a valuable tool for the study of the catecholamine oxidation process and its related toxicity. PMID- 17345574 TI - Rodlet cells and the sensory systems in zebrafish (Danio rerio). AB - This preliminary work was designed to study, using routine procedures for light and transmission electron microscopy, the presence of rodlet cells (RCs) in or near the sensory systems of 12 adult specimens (4.0 +/- 1.2 cm, LT +/- SD) of zebrafish, Danio rerio Hamilton, 1822. Rodlet cells, characterized by a distinctive cell cortex (range, 0.4-1.5 microm in thickness) and conspicuous inclusions named "rodlets," have a round to ovoid nucleus with irregular outline. Mature RCs are 11.5 +/- 1.2 microm (mean +/- SD) long and 7.8 +/- 1.1 microm (mean +/- SD) wide. These cells are more numerous near neuromasts enclosed by an epithelial roof and/or ossified canal wall. In contrast, very few RCs were noticed near superficial neuromasts. Based on the presence of RCs around the two cranial neuromasts of each fish, a variable number from 1 to 15 rodlet cells was found (10.4 +/- 3.6, mean +/- SD). The RCs were located 1.5 microm (minimal) to 73.3 microm (maximal) from the neuromast (27.9 +/- 17.2, mean +/- SD). Moreover, RCs were found in olfactory epithelium and in proximity to some taste buds. Interestingly, RCs were absent in the inner ear, eye, and brain. PMID- 17345575 TI - Masticatory muscles of the great-gray kangaroo (Macropus giganteus). AB - The great-gray kangaroo (Macropus giganteus) belongs to the Diprotodontia suborder (herbivorous marsupials of Australia) of the order of marsupials. We dissected the masticatory muscles in the great-gray kangaroo and classified them based on their innervation. Three (two male and one female) adult great-gray kangaroos (M. giganteus), fixed with 10% formalin, were examined. The masseter muscle of the great-gray kangaroo was classified into four layers (superficial layers 1, 2, 3, and a deep layer), all innervated by masseteric nerves. Layer 1 of the masseter muscle was well developed and the deep layer inserted into the masseteric canal. The zygomaticomandibular muscle, which belongs to both the masseter and temporalis muscles, was innervated by both the masseteric nerve and posterior deep temporal nerve, and the temporalis muscle was innervated by the anterior and posterior deep temporal nerves. The medial pterygoid muscle, which was innervated by the medial pterygoid nerve, was divided into superficial and deep portions. The lateral pterygoid muscle was divided into superior and inferior heads by the buccal nerve. We propose that the relationship of the masticatory muscles in the kangaroo has evolved by passive anterior invasion of the deep layer of the masseter by the medial pterygoid muscle via the masseteric canal, associated with the development of an anteroposterior mode of mastication. PMID- 17345576 TI - Production of polyvinyl alcohol-degrading enzyme with Janthinobacterium sp. and its application in cotton fabric desizing. AB - A strain capable of using polyvinyl alcohol (PVA) as sole carbon source was isolated from soil samples of a textile factory. The 16S rDNA sequence analysis cell morphology, physiology and biochemistry showed that it belonged to Janthinobacterium sp. This is the first report to show that the screened Janthinobacterium sp. could degrade PVA. The optimum nutritional and environmental conditions for PVA-degrading enzyme production by Janthinobacterium sp. were investigated by single-factor tests. Under optimized nutritional and environmental condition in shake flasks, PVA-degrading enzyme reached 5.12 U/mL at 21 h. With PVA-degrading enzyme produced by Janthinobacterium sp. WSH04-01, 80% of PVA could be degraded from cotton fabrics in 3 h. PMID- 17345577 TI - A multikinetic model approach to predict gluconic acid production in an airlift bioreactor. AB - This paper uses a multikinetic approach to predict gluconic acid (GA) production performance in a 4.5 L airlift bioreactor (ALBR). The mathematical model consists of a set of simultaneous firstorder ordinary differential equations obtained from material balances of cell biomass, GA, glucose, and dissolved oxygen. Multikinetic models, namely, logistic and contois equations constitute kinetic part of the main model. The main model also takes into account the hydrodynamic and mass transfer parameters. These equations were solved using ODE solver of MATLAB v6.5 software. The mathematical model was validated with the experimental data available in the literature and is used to predict the effect of change in initial biomass and air sparging rate on the GA production. It is concluded that the mathematical model incorporated with multikinetic approach would be more efficient to predict the change in operating parameters on overall bioprocess of GA production in an ALBR. PMID- 17345578 TI - Differential response to ischemia in adjacent hippocampalsectors: neuronal death in CA1 versus neurogenesis in dentate gyrus. AB - Two hippocampal sectors show distinct responses to transient ischemia: the cornu Ammonis (CA)1 sector undergoes a delayed neuronal death followed by a lack of neuronal generation, while the dentate gyrus (DG) shows slight postischemic damage followed by an increased neurogenesis. Using the monkey experimental paradigm of transient whole brain global ischemia, the 'calpain-cathepsin hypothesis' was formulated in 1998. This hypothesis proposes that following ischemia calpain compromises the integrity of lysosomal membrane, causing a leakage of degrading hydrolytic enzymes--cathepsins--into the cytoplasm. Ischemia induces Ca(2+) mobilization, calpain activation, lysosomal membrane disruption, and cathepsin release, which all occur specifically in the CA1 sector and cause neuronal death. In the postischemic DG, a vascular niche has been implicated in adult neurogenesis, in that adventitial cells of the DG microvascular environment provoke postischemic up-reguation of neurogenesis with the aid of brain-derived neurotrophic factor and polysialylated form of the neural cell adhesion molecule. In parallel, Down's syndrome cell adhesion molecule has recently been shown to be expressed specifically in the neural progenitor cells of DG. In this review, we focus on the monkey experimental paradigm to reveal the remarkable contrasts between CA1 and DG in response to the ischemic insult. PMID- 17345579 TI - Amyotrophic lateral sclerosis--the tools of the trait. AB - The aim of this review is to analyze how our knowledge on the etiology, pathology, and treatment of amyotrophic lateral sclerosis (ALS) has profited from the application of biotechnology tools for the identification of disease markers, the development of animal disease models, and the design of innovative therapeutics. In humans, ALS-specific clinical, genetic or protein biomarkers, or panels of biomarkers stemming from genomics and proteomics analyses can be critical for early diagnosis, monitoring of disease progression, drug validation in clinical trials, and identification of therapeutic targets for subsequent drug development. At the same time, animal models representing a number of human superoxide dismutase 1 mutations, intermediate-filament disorganization or axonal transport defects have been invaluable in unraveling aspects of the pathophysiology of the disease; in each case, these only represent a small proportion of all ALS patients. Preclinical and clinical trials, although at present heavily concentrating on pharmacological approaches, are embracing the emerging alternative strategies of stem-cell and gene therapy. In combination with a further subcategorization of patients and the development of corresponding model systems for functional analyses, they will significantly influence the already changing face of ALS therapy. PMID- 17345581 TI - Induction of organ-selective CD4+ regulatory T cell homing. AB - Compelling evidence suggests that Foxp3(+)CD25(+)CD4(+) Treg play a fundamental role in immunoregulation. We have previously demonstrated that Treg have to enter peripheral tissues to suppress ongoing inflammation. However, relatively little is known about how Treg acquire the expression of homing receptors required for tissue- or inflammation-specific migration. Migratory properties of conventional naive T cells are shaped by the tissue microenvironment and organ-specific dendritic cells during priming. Here, we show that this basic concept also holds true for CD25(+)CD4(+) Treg: Priming of Treg within peripheral LN led to the expression of selectin ligands, which facilitate migration into inflamed skin, whereas activation within mesenteric LN led to induction of the integrin alpha(4)beta(7), which is required for migration into mucosal tissues. Furthermore, we could establish in vitro culture systems containing either dendritic cells from mesenteric and peripheral LN, or retinoic acid and IL-12 as polarizing compounds to induce mucosa- and skin-seeking Treg, respectively. Together, our results demonstrate that Treg, similarly to conventional T cells, can be configured with organ-selective homing properties allowing efficient targeting into distinct tissues. PMID- 17345582 TI - An evolvable oestrogen receptor activity sensor: development of a modular system for integrating multiple genes into the yeast genome. AB - To study a gene interaction network, we developed a gene-targeting strategy that allows efficient and stable genomic integration of multiple genetic constructs at distinct target loci in the yeast genome. This gene-targeting strategy uses a modular plasmid with a recyclable selectable marker and a multiple cloning site into which the gene of interest is cloned, flanked by two long regions of homology to the target genomic locus that are generated using adaptamer primers. We used this strategy to integrate into a single yeast strain components of the oestrogen receptor (ER) signalling network, comprising the human ERalpha and three reporter genes driven by oestrogen response elements (EREs). The engineered strain contains multiple reporters of ligand-dependent receptor signalling, providing sensitive, reproducible, rapid, low-cost quantitative assays of ERalpha activity in order to screen potential receptor agonists. Further, because two of the ERE-driven reporter genes are required for growth in deficient media, the strain's growth rate-and therefore its fitness-depends on ligand-induced ERalpha activity. This evolvable oestrogen receptor activity sensor (EERAS) can therefore provide the foundation of a long-term experimental evolution strategy to elucidate ER structure-function relations and ligand-receptor evolution. PMID- 17345583 TI - Role in anaerobiosis of the isoenzymes for Saccharomyces cerevisiae fumarate reductase encoded by OSM1 and FRDS1. AB - Saccharomyces cerevisiae possesses both a cytoplasmic and a mitochondrial fumarate reductase, encoded by FRDS1 and OSM1, respectively. While previous studies have shown that mutants lacking FRDS1 and OSM1 cannot grow under anaerobiosis (Arikawa et al., 1998), the physiological role of fumarate reductase (FR) remains poorly understood. Here, we report that an osm1 frds1 mutant is unable to grow anaerobically, even with glutamate as a sole nitrogen source, when succinate can be produced by the TCA oxidative branch. We also show that the growth of the mutant is not restored by adding acetoin, an alternative sink for NADH oxidation, but it is at least partly restored by the addition of oxygen or menadione, which can oxidize FADH(2) in addition to NADH. These data indicate that the growth inhibition of the mutant is due to an inability to reoxidize FAD, rather than an indirect effect on NADH or an inability to produce succinate per se. During anaerobic growth, FRDS1 expression was two to eight times higher than that of OSM1, and fumarate reductase activity was higher in the osm1 mutant than in the frds1 mutant. FRDS1 expression was induced by anaerobiosis, and this induction was abolished in a rox1 mutant. We conclude that the formation of succinate is strictly required for the reoxidation of FADH(2) during anaerobiosis, and that it is regulated through the control of FRDS1 expression when oxygen is limiting. Based on these data, we discuss the potential role of fumarate reductase in the regeneration of the FAD-prosthetic group of essential flavoproteins. PMID- 17345580 TI - Categorical selection of the antibody repertoire in splenic B cells. AB - In the bone marrow, the passage of developing B cells through critical checkpoints of differentiation is associated with a reduction of specific categories of CDR3 of the Ig heavy chain (CDR-H3), particularly those with excessive hydrophobic or charged amino acids and those with a length of eight or fewer residues. To gain insight into the role of CDR-H3 content in the development of B cells in the spleen, we compared the sequences of V(H)7183DJCmu transcripts from sorted transitional T1, marginal zone, and follicular B cell subsets to those expressed by immature IgM(+)IgD(-) and mature IgM(lo)IgD(hi) B cells in the bone marrow. Although differences in V(H) utilization were noted, the T1 CDR-H3 repertoire showed extensive similarity to that of immature bone marrow B cells, and the follicular CDR-H3 repertoire most resembled that of mature bone marrow B cells. Unlike the splenic follicular and bone marrow mature B cell CDR-H3 repertoires, the marginal zone B cell CDR-H3 repertoire retained both short and highly charged amino acid motifs, including those with two arginines. Our findings suggest that antigen binding sites containing specific categories of CDR-H3 sequence content may inhibit, permit, or even facilitate passage of the host B cell through critical checkpoints in peripheral as well as central development. PMID- 17345584 TI - Prenatal diagnosis in monozygotic twins with Down syndrome who had different phenotypes. AB - We report the case of monozygotic (MZ) male twin fetuses with different Down syndrome (DS) phenotypes. Prenatal fetal sonography showed a bichorial biamniotic pregnancy with increased nuchal translucency in twin A and a cervical cystic hygroma and heart defect in twin B. Cytogenetic analysis performed after double amniocentesis showed free and homogeneous trisomy 21 in both twins. Monozygosity was confirmed by molecular analysis. The pregnancy was terminated at 17 weeks of gestation (WG). Postmortem analysis confirmed the phenotypic discordance. To our knowledge, this is the first reported prenatal diagnosis of MZ male twins with different Down syndrome phenotypes but identical karyotypes. We discuss the mechanisms involved in phenotypic discordance of monozygotic twins and particularly the role of environmental factors. PMID- 17345585 TI - Health literacy and patient understanding of screening tests for aneuploidy and neural tube defects. AB - OBJECTIVE: To determine if health literacy is associated with patient understanding of prenatal screening tests for fetal aneuploidy and neural tube defects. METHODS: We performed a prospective observational study on a cohort of English-speaking patients receiving prenatal care in two resident-staffed ambulatory clinics. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine-7. Understanding of the prenatal screening tests was assessed using a modified Maternal Serum Screening Knowledge Questionnaire. RESULTS: Over an 8-month period, 125 patients were approached, and 101 (81%) consented to the study. Thirty-eight (38%) women demonstrated low health literacy. Patients with low health literacy were more likely to demonstrate inadequate understanding when compared to those with adequate health literacy (97% versus 11%, respectively; P < 0.01). Similarly, patients with < 12th grade education were more likely to have inadequate understanding when compared to patients with > 12th grade education (53% versus 30%, respectively; P = 0.02). Health literacy is a more sensitive and specific predictor of inadequate understanding than education (sensitivity 84% versus 70%, respectively, P < 0.05; specificity 98% versus 47%, respectively, P < 0.05). CONCLUSION: Patients with low health literacy are more likely to demonstrate inadequate understanding of these prenatal screening tests than women with adequate health literacy. PMID- 17345586 TI - Prenatal sonographic findings and hematological abnormalities in fetuses with transient abnormal myelopoiesis with Down syndrome. AB - OBJECTIVES: To determine relevant prenatal findings of transient abnormal myelopoiesis (TAM) that have important prognostic implications. METHODS: The prenatal and postnatal medical records of all cases with confirmed TAM associated with Down syndrome were reviewed retrospectively, with emphasis on prenatal sonographic findings, fetal blood analysis, neonatal outcomes, and causes of death. RESULTS: From January 1992 to December 2005, seven cases were confirmed postnatally as having TAM associated with Down syndrome. Sonography demonstrated hydrops with hepatomegaly in four, and isolated hepatomegaly in two of these seven cases. There were no findings suggestive of cardiac failure in cases of hydrops. Fetal blood analysis revealed elevated liver enzyme levels in six cases and hypoalbuminemia in four cases. Comparison of sonographic findings with fetal blood findings demonstrated an association between hydrops and hypoalbuminemia. Four of the seven cases were fatal. All fatal cases were associated with hydrops and the main cause of death was coagulopathy due to liver failure, which may have resulted from infiltration of the liver by blast cells. CONCLUSIONS: Fetal TAM is associated with hepatomegaly and elevated liver enzyme levels. The prenatal finding with prognostic implications is hydrops, which may result from hypoalbuminemia due to liver failure. PMID- 17345587 TI - Acute oral toxicity of colchicine in rats: effects of gender, vehicle matrix and pre-exposure to lipopolysaccharide. AB - The oral toxicity of a single administration by gavage (10, 20 or 30 mg kg(-1) body weight) of colchicine (COL) was determined in young, mature male and female Sprague-Dawley rats. The effect of COL was evaluated in the presence or absence of additional treatment variables that included vehicle and lipopolysaccharide (LPS) pre-exposure. The vehicle for COL was either Half and Half cream (H & H) or saline, and each group included pretreatment with either saline or a low, minimally toxic dose (83 microg kg(-1) body weight) of LPS. Colchicine toxicity in both male and female age-matched rats was characterized by progressively more severe dose-related clinical signs of toxicity. These included mortality, decreased body weight and feed intake during the first several days after dosing, with recovery thereafter in surviving animals. There were differences in the severity of the toxic response to COL between male and female rats. The most notable sex-related difference was in COL lethality. Female rats were two times more susceptible to the lethal effects of COL than male rats. Saline or H & H delivery vehicles did not result in any apparent qualitative or quantitative differences in COL toxicity. LPS pretreatment significantly potentiated COL lethality in both males and females, although the potentiation in males was greater than in females. LPS pretreatment modestly increased the COL induced anorexic effect in surviving males, but not in surviving female animals. LPS did not appear to modulate either the body weights or clinical signs of COL induced toxicity in surviving males or females. PMID- 17345588 TI - Rehabilitation of surgical cancer patients at University of Texas M. D. Anderson Cancer Center. AB - With early detection and treatment, survival rates for many types of cancer have improved. Long term survivors have number of issues, which can include functional deficits, pain, fatigue, lymphedema and altered bowel and bladder function. Simple activities such as mobility and the ability to perform self care can be limited. In addition, re-integration into society with activities such as driving, social interaction and return to work are often problematic. The goal of cancer rehabilitation is to improve quality of life by minimizing disability and handicap caused by cancer and associated treatments. Initial rehabilitation interventions usually occur in an inpatient setting as patients often experience a decline in functional status due to cancer progression and or surgical treatment. Rehabilitation interventions reduce the debility and functional deficits and add to the quality of life for cancer patients undergoing surgical treatments. The rehabilitation team can assist not only with acute decline in functional status but also with re-integration back in society. Both general and specific rehabilitation interventions based on diagnoses are reviewed. PMID- 17345589 TI - Linkage to a known gene but no mutation identified: comprehensive reanalysis of SPG4 HSP pedigrees reveals large deletions as the sole cause. PMID- 17345590 TI - Modified radiofrequency-assisted liver resection: a new device. AB - BACKGROUND: Radiofrequency ablation (RF) is emerging as new therapeutic method for the management of hepatic tumors. So far the RF-assisted hepatectomy has been described using an electrode initially designed for ablation of unresectable tumors. Herein, we describe a new technique for liver resection using a bipolar radiofrequency device. METHOD: Ten patients undergo liver resection using a bipolar radiofrequency device. A minimal zone of desiccation around the tumor is created between pairs of opposing electrodes as a result of a minimum amount of energy released. This coagulated plane can be divided with a scalpel. RESULTS: The liver parenchyma was divided with minimal blood loss. No intensive care unit admission was needed. There was no postoperative biliary leak or any other septic complication. CONCLUSION: The technique is safe and feasible, simplifies liver resection and appears to be associated with minimal morbidity and maximum liver parenchyma preservation. PMID- 17345591 TI - MR-guided ablation of hepatocellular carcinoma aided by gadoxetic acid. AB - Local recurrences are problematic following radiofrequency ablation (RFA) of hepatocellular carcinoma. Intraoperative magnetic resonance imaging (iMRI) is a potentially useful tool for the assessment of the extent of the thermal injury produced by RFA. The use of gadoxetic acid disodium, a hepatocyte-specific contrast agent with prolonged retention, is described as a method of improved assessment of the ablative margins relative to the tumor margins. PMID- 17345592 TI - A simple nerve dissecting technique for identification of marginal mandibular nerve in radical neck dissection. PMID- 17345593 TI - Serum insulin-like growth factor I/free prostate specific antigen (IGF-I/fPSA) ratio enhances prostate cancer detection in men with total PSA 4.0-10.0 ng/ml. AB - BACKGROUND: Recent studies have suggested that IGF-I and IGFBP-3, in combination with PSA, may enhance PCa detection. This study was to investigate the use of serum IGF-I and IGFBP-3, and their combinations with prostate volume and fPSA in enhancing the discriminatory diagnosis of PCa in men with tPSA of 4.0-10.0 ng/ml. METHODS: Serum IGF-I and IGFBP-3 were determined by ELISA from 586 men with tPSA between 4.0 and 10.0 ng/ml. Of them, 281 were diagnosed with PCa and 305 without. ROC, univariate and multivariate logistic regression analyses were performed to evaluate the predictive performance of those parameters. RESULTS: IGF-I, IGFD, IGF-I/fPSA, and IGFBP-3/fPSA were significantly higher in PCa cases than benign controls, whereas the differences of IGFBP-3 and IGFBPD were statistically insignificant between the two groups, respectively. The AUC values indicated enhanced performance of IGF-I/fPSA ratio (AUC = 0.753) in PCa detection compared with the currently used f/tPSA (AUC = 0.689). Multivariate logistic regression confirmed the observed relationships and identified IGF-I/fPSA as independent factor in PCa presence. CONCLUSION: Our data show that IGF-I/fPSA as a promising marker can enhance PCa detection in ambiguous cases often found in the tPSA between 4.0 and 10.0 ng/ml. PMID- 17345594 TI - High operative risk of cool-tip radiofrequency ablation for unresectable pancreatic head cancer. PMID- 17345595 TI - Barriers to rehabilitation of patients with extremity sarcomas. AB - The treatment of most extremity bone or soft tissue sarcomas involves either limb salvage surgery with adjuvant chemoradiation therapy or amputation. The rehabilitation of patients with extremity sarcomas is challenging, and the approach differs depending on the choice of surgical procedure as well as potential-associated medical complications. Early, interdisciplinary rehabilitation involvement is helpful in lessening the impact of expected impairments and disability. There is a lack of evidence examining specific rehabilitation interventions in this patient population. Functional outcomes and quality of life studies suggest overall similar findings between limb salvage patients and amputees, but with differences in various subscales. Rehabilitation interventions are therefore individualized; based on the assessment of medical limitations, functional goals and expectations, and modification of environmental factors. Overcoming medical and oncologic barriers to rehabilitation; as well as psychological, structural, cultural, political, and economic barriers; can serve to lessen the degree of disability. PMID- 17345596 TI - What is the best treatment modality for adrenal metastasis from hepatocellular carcinoma? AB - PURPOSE: This study aimed to analyze the effect of each therapeutic modality to clarify the treatment strategy for adrenal metastases from hepatocellular carcinoma (HCC). METHODS: Adrenal metastasis from HCC was observed in 45 patients. Fifteen patients who were determined to have multi-organ metastasis including the adrenal glands were excluded, and the remaining 30 patients were reviewed. RESULTS: The location of adrenal metastasis was right side, left side, and both in 17, 9, and 4 patients, respectively. Treatment for adrenal metastasis consisted of adrenalectomy in 5 patients, non-surgical treatment such as TACE, or chemotherapy and radiotherapy in 19 patients, while 6 patients received no treatment. The median survival duration was 11.05 months in the 30 patients with adrenal metastasis. In the 25 patients with well-controlled intrahepatic lesions, the median survival time of those patients who received adrenalectomy, non surgical treatment, and no treatment was 21.41, 11.05, and 5.64 months, respectively. The difference in cumulative survival according to mode of treatment of adrenal metastasis in the well-controlled intrahepatic lesion group was statistically significant. CONCLUSION: We envisage increased benefit after adrenalectomy in terms of survival in patients with well controlled intrahepatic lesions at the time of adrenal metastasis and good general medical condition. PMID- 17345597 TI - Incidence and prognostic values of lymph node metastasis in operable hepatocellular carcinoma and evaluation of routine complete lymphadenectomy. AB - BACKGROUND: To study lymph node metastasis (LNM) and prognosis in patients with operable hepatocellular carcinoma (HCC) as well as the value of routine complete lymphadenectomy. Few studies have been reported on LNM in patients with operable HCC. METHODS: Lymph node enlargement of 968 patients with operable HCC was carefully explored and LNM was diagnosed by typical intraoperative findings or pathology. RESULTS: Forty-nine (5.1%) patients had LNM, which was associated with advanced tumor properties. The 1-, 3-, and 5-year overall survival in patients with LNM was poorer than those without LNM (62.0%, 31.0%, and 26.0% vs. 81.0%, 62.0%, and 47.0%, P = 0.000). The 1-, 3-, and 5-year overall survival in patients who received complete lymphadenectomy (n = 26) was poorer than those without LNM (68.0%, 31.0%, and 31.0% vs. 81.0%, 62.0%, and 47.0%, P = 0.017), and was not better than patients who received chemotherapy or radiotherapy (P = 0.944). CONCLUSION: The incidence of LNM in operable HCC patients was low, and patients with LNM had a poorer prognosis. LNM status determined the disease-free survival but not the overall survival of HCC. The complete lymphadenectomy did not improve overall survival, as compared with chemotherapy or radiotherapy. PMID- 17345598 TI - Barriers to rehabilitation of colorectal cancer patients. AB - BACKGROUND: Colorectal cancer is one of the most common cancers in the United States. Since 1993 there has been a decrease in colorectal cancer mortality. Thus, there are more cancer survivors. In this manuscript potential barriers encountered during the rehabilitation of the colorectal cancer patient will be discussed. METHODS: A literature review of manuscripts dealing with the rehabilitation and quality of life of the colorectal cancer patient was performed with specific emphasis on barriers for rehabilitation. RESULTS: There is not much literature regarding barriers to the rehabilitation of the colorectal cancer patient. The rehabilitation of the colorectal cancer patient is a complex continuum. In order to maximize the potential for rehabilitation a team approach where the patient, family, friends and health care providers participate actively should be undertaken. The most common barriers are in the domains of knowledge, patient, health care system, and therapy. The impact of these barriers will vary from patient to patient. CONCLUSIONS: There is a paucity of literature regarding barriers to the rehabilitation of the colorectal cancer patient. Prospective databases as well as prospective longitudinal studies need to be established so that the barriers that colorectal cancer patients encounter during their rehabilitation are more clearly identified and understood. PMID- 17345599 TI - Chest wall defect reconstruction with cotranlateral breast. PMID- 17345600 TI - Obsessive-compulsive disorder in youth with and without a chronic tic disorder. AB - The goal of this study was to discriminate subtypes of pediatric obsessive compulsive disorder (OCD) among youth with and without a comorbid tic disorder. Seventy-four youth (M(age)=9.7+/-2.3 years) with a principal diagnosis of OCD, with (n=46) or without (n=28) a comorbid tic disorder, were assessed with a semi structured diagnostic interview and the Children's Yale Brown Obsessive Compulsive Scale (CY-BOCS). The CY-BOCS Symptom Checklist was used to categorize obsessions and compulsions. Group differences were analyzed by t tests, chi(2), and discriminant function analyses. Results suggested that subjects without tics had significantly more contamination obsessions, sexual obsessions, and counting compulsions than youth with comorbid tics. Generally speaking, however, youth with and without tics had similar symptom presentations. These data suggest that pediatric OCD patients with and without comorbid tics may have some aspects of symptom presentation that differ, but generally have more OCD symptoms in common than different. Implications of these findings on clinical presentation and treatment efficacy are highlighted. PMID- 17345601 TI - Major depression: the relative contribution of gender, MDMA, and cannabis use. AB - Previous research has suggested that 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) users have elevated depressive symptomatology, although it is not clear whether this is due to MDMA or other drug use. This study aimed to investigate the contributions of MDMA and cannabis use to Major Depressive Disorder in MDMA users. A total of 226 MDMA users were studied. Participants (65% male) reported an average number of 35.8 uses of MDMA (SD = 45.6, range = 2-400). Participants were administered a Structured Clinical Interview for DSM-IV. Twenty-six individuals (11.5%) met lifetime criteria for Major Depressive Disorder. High rates of lifetime Cannabis Abuse (30.1%) and Cannabis Dependence (12.4%) were reported. No association was found between number of uses of MDMA and Major Depressive Disorder. Those with lifetime major depression were found, however, to have higher rates of lifetime cannabis use disorder (adjusted OR = 2.40). A logistic regression indicated that lifetime cannabis use disorder, but not MDMA use, was significantly associated with lifetime Major Depressive Disorder. Stratified analyses suggested that for males, neither drug use variable was associated with major depression. For females, a lifetime cannabis use disorder (adjusted OR = 4.99), but not MDMA use, was associated with lifetime Major Depressive Disorder. Results of this study suggest that although MDMA use was not found to be significantly associated with major depression for either gender, a lifetime cannabis use disorder was significantly associated with lifetime major depression for female, but not male, users of MDMA. PMID- 17345602 TI - Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia. AB - Null mutations in the progranulin gene (GRN, PGRN) were recently identified as the causal mechanism underlying frontotemporal dementia (FTD) with ubiquitin positive brain pathology linked to chromosome 17 (FTDU-17). In a Belgian and French FTD series comprising 332 patients, we reported 13 PGRN null mutations which were mainly nonsense and frameshift mutations resulting in premature stop codons. Here we report in the same patient series three missense mutations of which two (c.743C>T, p.Pro248Leu and c.1294C>T, p.Arg432Cys) were predicted in silico to severely affect protein folding and/or processing leading to PGRN protein haploinsufficiency. In addition, we observed three sequence variations in the 5' regulatory region that might potentially affect PGRN transcription activity. Our findings extend the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for FTD. PMID- 17345604 TI - Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. AB - Leber congenital amaurosis (LCA) is the earliest and most severe retinal degeneration responsible for congenital blindness. Hitherto, 13 LCA genes have been mapped, nine of which have been identified. Recently, mutations in the NPHP6/CEP290 gene were shown to account for Joubert and Senior-Loken syndromes and to represent a frequent cause of isolated LCA. All LCA patients shared an intronic mutation resulting in an aberrantly spliced transcript and low levels of wild-type transcript that was believed to explain the absence of cerebellar and renal involvement in these patients. Here, we confirm the high frequency of NPHP6/CEP290 mutations in our series of LCA families hailing worldwide (22%). However, we show that conversely to other LCA genes, NPHP6 is involved in families of European descent only (38/38). A total of 24 different mutations were found, 23 of which are novel (one founder mutation in the North region of France). All mutations but two were either nonsense, frameshift, or splice-site changes. The common NPHP6/CEP290 intronic mutation accounted for 43% (33/76) of all disease alleles. Twelve families did not carry this common intronic mutation. At least 10 out of them harboured two mutations expected to truncate the protein questioning the relevance of the assumption according to which the retinal restricted phenotype in LCA patient could be due to a residual NPHP6/CEP290 activity. Finally, we show that all patients were affected with the cone-rod subtype of the disease whatever their NPHP6/CEP290 genotype. PMID- 17345603 TI - Demographic and clinical characteristics associated with treatment status in family members with obsessive-compulsive disorder. AB - This study investigated the demographic and clinical factors that influence treatment status in family members with obsessive compulsive disorder (OCD). Six hundred and two subjects from the OCD Collaborative Genetics Study were interviewed using the Structured Clinical Interview for DSM-IV (SCID) to diagnose Axis I disorders, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for assessment of OCD symptoms. The demographic and clinical data were compared between subjects who had received treatment and those who had not. A precipitous onset of symptoms, severe illness, multiple obsessions and compulsions, and co morbid affective disorders were all positively associated with receiving treatment. Older age and the presence of obsessive compulsive personality disorder (OCPD) or OCPD traits were negatively associated with treatment. Gender and age at onset of symptoms did not predict treatment history. The mean duration from onset of symptoms to receiving treatment was 13.8+/-SD 11.9 years, but there was a direct relationship between current age and time to treatment, with younger subjects receiving treatment sooner. Clinical factors are predominant in predicting treatment status in family members with OCD. Although the mean duration from onset of symptoms to treatment was long, younger family members appear to receive treatment sooner. PMID- 17345605 TI - Infliximab and the risk of latent viruses reactivation in active Crohn's disease. AB - BACKGROUND: Infliximab is used for refractory Crohn's disease but there are concerns regarding long-term safety. Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses. METHODS: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein-Barr virus (EBV), human herpes virus-6, (HHV-6), -7, -8, and cytomegalovirus (CMV). RESULTS: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV-positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV-PCR tests were transiently positive (>40 copies/10(5) Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV-6, -7, and -8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV-PCR-positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. CONCLUSIONS: Our results support the safety of short-term infliximab treatment with respect to latent virus reactivation. The long-term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring. PMID- 17345607 TI - Spondylodiscitis representing as the very first sign of Crohn's disease. PMID- 17345608 TI - Complications in Crohn's disease: right-sided ureteric stenosis and hydronephrosis. PMID- 17345609 TI - Smoking and inflammatory bowel disease: trends in familial and sporadic cohorts. AB - BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) result from genetic and environmental factors. Never smoking and formerly smoking increase the risk of UC, whereas smoking exacerbates the course of CD. We sought to define the age dependent effects of smoking on the development of UC and CD in familial and sporadic cohorts. METHODS: University of Chicago patients diagnosed with UC or CD between 1990 and 2002 were surveyed about their tobacco use relative to their diagnosis. Smoking trends were used to estimate age-dependent odds ratios and the attributable risks of smoking in the IBD cohort compared to in the general population. RESULTS: One thousands and thirteen patients were included in the study: 245 with sporadic UC; 216 with sporadic CD; 249 with familial UC; and 303 with familial CD. Being an ex-smoker conferred an increased risk for UC in the 25 44 age group in both the sporadic and familial cohorts, but not in the 45-64 age group in the familial UC cohort. Furthermore, there was no difference in tobacco use between patients with sporadic CD and the general population, although there was a significant increase in smoking in younger patients with familial CD. CONCLUSIONS: Ex-smokers make up an increasing percentage of older patients diagnosed with UC, accounting for more than 35% of the attributable risk of late onset (>45 years) UC and a large component of the second peak in diagnosis. Current smokers account for a large percentage of patients diagnosed at a younger age with familial CD but not with sporadic CD. Families with IBD should be counseled that early tobacco use significantly increases the risk of developing CD or, if an ex-smoker, UC at a young age. PMID- 17345610 TI - What is a sentinel node? Re-evaluating the 10% rule for sentinel lymph node biopsy in melanoma. AB - INTRODUCTION: Many surgeons use the "10% rule" to define whether a lymph node is a sentinel node (SLN) when staging malignant melanoma. However, this increases the number of SLN removed and the time and cost of the procedure. We examined the impact of raising this threshold on the accuracy of the procedure. METHODS: We reviewed the records of 561 patients with melanoma (624 basins) who underwent SLN with technetium Tc99 labeled sulfur colloid using a definition of a SLN as 10% of that of the node with the highest counts per minute (CPM). RESULTS: Of the 624 basins, 154 (25%) were positive for metastases. An average of 1.9 nodes per basin were removed (range 1-6). Metastases were found in the hottest node in 137 cases (89% of positive basins, 97% of basins overall). Increasing the threshold above 10% decreased the number of nodes excised and the costs involved, but incrementally raised the number of false negative cases above baseline (a 4% increase for a "20% rule," 5% for a "30% rule," 6% for a "40% rule," and 7% for a "50% rule"). Taking only the hottest node would raise the false negative rate by 11%. CONCLUSIONS: Although using thresholds higher than 10% for the definition of a SLN will minimize the extent of surgery and decrease the costs associated with the procedure, it will compromise the accuracy of the procedure and is not recommended. PMID- 17345611 TI - Local and distant control in non-metastatic pelvic Ewing's sarcoma patients. AB - BACKGROUND AND OBJECTIVES: Due to possible complication and loss of function, surgery is not often indicated in pelvic Ewing's sarcoma (ES). The purpose of this study was to review our experience and evaluate the role of different local treatment in non-metastatic pelvic ES patients. METHODS: One hundred twenty-nine patients with pelvic ES were treated at our institution between 1975 and 1999. We excluded patients presenting metastases, patients who had died of other causes, or those with incomplete clinical documentation. Among the 73 eligible patients, 17 (23%) with progression of tumor growth during induction chemotherapy eventually died. The analysis was focused on the remaining 56 patients with good or stable clinical response to the chemotherapy. RESULTS: Patients treated with surgery, with or without radiation therapy, had a better local control (82.6% vs. 66.7%) and a significantly higher rate of 5-year EFS (73.9% vs. 30.3%, P = 0.036) than those who were only treated with local radiation therapy. CONCLUSION: Chemotherapy is the key factor in the treatment of pelvic ES. In our series, surgical treatment was associated with good prognosis for pelvic ES. The use of radiotherapy alone was less effective and should be only used in non-operable patients. Radiotherapy after surgery as a rescue method might not act effectively, while preoperative radiotherapy was associated with good clinical response and should be recommended. PMID- 17345612 TI - Myelodysplastic syndromes: incidence and survival in the United States. AB - BACKGROUND: Myelodysplastic syndromes (MDS) became reportable to the Surveillance, Epidemiology, and End Results (SEER) Program (the United States cancer surveillance program) in 2001. This provided the first opportunity to examine the incidence and survival of patients with MDS in the United States using a large, population-based database. METHODS: The SEER 17 regions public-use database (November 2005 submission) was accessed to obtain data on the frequency, incidence, and survival of patients with MDS. Geographic areas were selected for inclusion in the SEER Program based on their ability to operate and maintain a high-quality, population-based cancer reporting system and for their epidemiologically significant population subgroups. RESULTS: SEER data from 2001 through 2003 indicated that the risk of MDS increased with age, and approximately 86% of MDS cases were diagnosed in individuals aged > or =60 years (median age at diagnosis = 76 years). Men had a significantly higher incidence rate than women (4.5 vs 2.7 per 100,000 per year). Among racial groups, white individuals had the highest incidence rate. In 2003, approximately 10,300 incident cases of MDS were diagnosed in the United States. The survival of MDS patients was poor, with an observed 3-year survival rate of only 35% (5-year survival data were not available at the time of the current report). Male patients and patients who were diagnosed at an older age had significantly worse survival. MDS survival also varied by clinical subtype, and the survival of patients who had refractory anemia was somewhat worse than reported previously. The availability of descriptive epidemiologic data on MDS can be used now to facilitate much needed research on the etiology and outcome of MDS. CONCLUSIONS: The current results indicated that >10,000 incident cases of MDS are diagnosed annually in the United States, and the survival of patients with MDS is poor. The availability of descriptive epidemiologic data on MDS can be used now to facilitate much needed research on the etiology and outcomes of MDS. PMID- 17345613 TI - Prophylaxis of Pneumocystis carinii pneumonia with atovaquone in children with leukemia. AB - BACKGROUND: Despite extensive studies of atovaquone in human immunodeficiency virus (HIV)-infected patients, there is little information about its efficacy as a prophylactic agent for Pneumocystis carinii pneumonia (PCP) in pediatric patients with cancer. Therefore, a retrospective analysis was conducted to determine the incidence of PCP in pediatric patients who received prophylactic atovaquone during treatment for acute leukemia. METHODS: We reviewed the medical records of all patients treated at our institution for acute lymphoblastic leukemia or acute myeloid leukemia between 1994 and 2004. Only patients who were intolerant of trimethoprim-sulfamethoxazole (TMP-SMZ) and received atovaquone prophylaxis were included in the analysis. RESULTS: Eighty-six patients were unable to tolerate TMP-SMZ and received daily atovaquone for PCP prophylaxis. PCP was not diagnosed in any patient who received atovaquone prophylaxis: the upper limit of the 95% confidence interval (CI) was 1.74 per 100 person-years. CONCLUSIONS: Atovaquone is an efficacious alternative for PCP prophylaxis in pediatric patients who have leukemia and are intolerant of TMP-SMZ. PMID- 17345614 TI - Preoperative interleukin-6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma. AB - BACKGROUND: Colorectal cancer is one of the most common forms of cancer in the Western world. Staging based on histopathology is currently the most accurate predictor of outcome after surgery. Colorectal cancer is curable if treated at an early stage (stage I-III). However, for tumors in stages II and III there is a great need for tests giving more accurate prognostic information defining the patient population in need of closer follow-up and/or adjuvant therapy. Furthermore, tests that provide prognostic information preoperatively could provide a guide both for preoperative oncologic treatment and the surgical procedure. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated preoperatively, within a week before primary surgery, from 39 patients undergoing surgery for colorectal cancer. The PBMCs were cultured in vitro for 24 hours in the presence of autologous serum and lipopolysaccharide (LPS). Interleukin-6 (IL 6) production was measured with enzyme-linked immunosorbent assay (ELISA). Staging based on histopathology was performed in all patients. Patients were followed for at least 54 months. RESULTS: A production of >5000 pg/mL of IL-6 identified colorectal cancer patients with a poor prognosis. Eight out of 13 patients with >5000 pg/mL IL-6 died from cancer within the follow-up period, whereas no cancer-related deaths were recorded among 21 patients with 5000 pg/mL IL-6 or less. A multivariate Cox regression analysis, stratified for T- and N stage, identified IL-6 production as an independent prognostic factor. CONCLUSIONS: IL-6 production in vitro by PBMC can predict survival after radical surgery for colorectal cancer. PMID- 17345615 TI - Resection and reconstruction of retrohepatic vena cava without venous graft during major hepatectomies. AB - BACKGROUND: Progress in liver surgery has enabled hepatectomy with concomitant venous resection for liver malignancies involving the inferior vena cava (IVC). The authors describe an alternative technique for IVC reconstruction without the need of graft. METHODS: Parenchymal transection is performed from anterior surface of the liver down to the anterior or left lateral surface of the IVC using combination of two techniques reported elsewhere. IVC is clamped above and below the tumor and the liver in continuity with an invaded segment of IVC is removed en bloc. A transverse anastomosis of IVC is performed starting with running suture on the posterior wall followed by the anterior wall. RESULTS: This approach has been successfully employed in eight consecutive patients with IVC involvement. The procedures performed were 5 right hepatectomies, 1 right posterior sectionectomy, 1 right trisectionectomy, and 1 left trisectionectomy. Two patients needed total vascular exclusion (TVE) for 11 and 10 min, respectively. Blood transfusion was necessary in three patients. Pathologic surgical margins were free in all cases. No postoperative mortality was observed. CONCLUSION: This technique of IVC reconstruction precludes the use of graft and minimizes the use of TVE decreasing ischemic damage to the remnant liver. PMID- 17345616 TI - Occult pancreaticobiliary reflux in gallbladder cancer and benign gallbladder diseases. AB - BACKGROUND AND OBJECTIVES: It was proposed that occult pancreaticobiliary reflux (OPBR) was associated with precancerous mucosal changes in the gallbladder, hence the importance of this disorder. There are no published reports investigating the incidence of OPBR in patients operated on for the entire spectrum of benign gallbladder diseases and gallbladder cancer. Our aim was to determine the incidence of OPBR and measure the levels of active pancreatic enzymes (amylase and lipase) in gallbladder bile of patients undergoing cholecystectomy for benign and malignant gallbladder diseases. METHODS: One hundred eight patients with normal pancreaticobiliary junction evidenced by operative cholangiography were included in the study. RESULTS: According to gallbladder bile amylase and lipase levels, 84.2% and 89% patients respectively had OPBR. OPBR was present in all gallbladder cancer patients; in these patients the biliary levels of amylase and lipase were significantly higher than the levels found in patients with benign gallbladder pathology (P < 0.0001). CONCLUSIONS: OPBR could lead to inflammatory changes of the biliary epithelium and progress towards the development of precancerous mucosal changes and gallbladder cancer. The reason why such high levels of pancreatic enzymes are regurgitated into the biliary tree of patients with gallbladder cancer should be clarified. PMID- 17345617 TI - Prognostic value of tumor thickness in patients with Merkel cell carcinoma. AB - BACKGROUND AND OBJECTIVES: Merkel cell carcinoma is an aggressive skin malignancy that often presents with tumor metastases. We hypothesized that tumor thickness might correlate with both regional and metastatic tumor spread and could, therefore, be used as an independent prognostic variable. The purpose of this study was to see if depth of tumor invasion would predict prognosis independent of tumor stage. METHODS: Data pertaining to clinical presentation, pathology, treatment, and survival were collected for patients diagnosed with Merkel cell carcinoma from 1972 to 2005. Patients were staged according to AJCC guidelines. Pathologic specimens were evaluated for tumor thickness. The relationship between tumor thickness and disease-free survival or overall survival was analyzed using Kaplan-Meier survival analyses. RESULTS: Sixty patients were identified. Five year disease-free survivals for Stages 1, 2, and 3 patients were 20%, 33%, and 0%, respectively. Five-year overall survivals for Stages 1, 2, and 3 patients were 33.3%, 60%, and 16.7%, respectively. There was no correlation between tumor thickness and either disease-free survival or overall survival. CONCLUSIONS: This study suggests that tumor thickness is not an independent risk factor for survival. Mean tumor thickness did increase with the AJCC stages, but this most likely represents more advanced stage of disease. PMID- 17345618 TI - Epstein-Barr virus-associated B-cell lymphoma in a patient with DNA ligase IV (LIG4) syndrome. AB - A 14-year-old Japanese girl with a progressing combined immunodeficiency had developed non-Hodgkin's diffuse large B cell lymphoma. Her molecular analysis showed a compound heterozygote of novel mutations in the LIG4 gene, M249V substitution and a five nucleotides deletion from nucleotide position 1,270 1,274. She had also a set of characteristic clinical features of LIG4 syndrome. Mutations in the LIG4 gene, which plays a critical role in the repair of DNA double-strand breaks, imply a correlation with malignancies and several cases with leukemia or lymphoma have already been reported. We report here on a case of LIG4 syndrome complicated with distinct EBV-associated B-cell lymphoma. PMID- 17345619 TI - Barriers to rehabilitation of the neurosurgical spine cancer patient. AB - The treatment of metastatic spine tumors has evolved significantly over the past 20 years due largely to improvements in magnetic resonance imaging; decompressive surgical techniques, spinal instrumentation, and high-dose conformal radiation. These advances have improved our ability to provide meaningful palliation for patients who often have significant medical and cancer-related issues. Despite technical advances that have improved our ability to maintain neurologic function, stabilize the spine, and prevent local tumor recurrences, significant barriers to rehabilitation remain. This article reviews these primary barriers to rehabilitation of the cancer patient following spine surgery and emphasizes the importance of diagnostic accuracy and a comprehensive team approach to the treatment of pain and other disorders in this population. PMID- 17345620 TI - Microarray comparative genomic hybridization and FISH studies of an unbalanced cryptic telomeric 2p deletion/16q duplication in a patient with mental retardation and behavioral problems. AB - We describe a 7-year-old patient with pervasive developmental disorder and behavioral problems who has a de novo cryptic unbalanced der(2)t(2;16)(p25.3;q24.3) chromosome resulting in deletion of distal 2p and duplication of distal 16q. These segmental aneusomies were detected by microarray comparative genomic hybridization analysis, as was a distal 17p13.3 duplication that was inherited from her father. FISH analysis using bacterial artificial chromosomes confirmed a deletion of approximately 1,700 kbp of DNA from 2pter (containing at least six complete genes or transcription units) and a duplication of approximately 500 kbp from 16qter (including up to ten genes or transcription units). Several genes in these regions are plausible candidates for contributing to the patient's phenotype. PMID- 17345621 TI - Monozygotic twins of Smith-Magenis syndrome. PMID- 17345622 TI - Alternative denervation using laser irradiation in lumbar facet syndrome. AB - BACKGROUND AND OBJECTIVE: Facet syndrome is persistent low back pain that might be treated with some surgical interventions. The target of surgical techniques is the transverse process bases where the medial nerve branches innervated the facet. However, highly variable success rates have been demonstrated in different series. STUDY DESIGN/MATERIALS AND METHODS: We carried out laser denervation to the dorsal surface of the facet capsule, where it is richly innervated with medial nerve branches. RESULTS: One year after laser denervation, 17 patients (81%) experienced complete or greater than 70% pain reduction in all 21 patients. Among the six patients who had previously undergone spinal surgery, two (33.3%) experienced successful pain relief. Overall, in four patients (19%), the response to laser denervation at 1-year follow-ups was not successful. CONCLUSION: The dorsal surface of the facet capsule might be a more preferable target for facet denervation. PMID- 17345623 TI - Correlation of photodynamic activity and fluorescence signaling for free and pegylated mTHPC in mesothelioma xenografts. AB - BACKGROUND/OBJECTIVES: Correlation of photodynamic activity (PDT) and fluorescence signaling for free and pegylated meta-tetrahydroxyphenylchlorin (mTHPC) in nude mice with mesothelioma xenografts. STUDY DESIGN/MATERIALS AND METHODS: Twelve animals received light delivery (20 J/cm(2), 150 mW/cm(2), spot size 1.2 cm) on the tumor and the hind leg 3 days after sensitization with 0.15 mg/kg free mTHPC (n = 6) or equimolar-dosed pegylated mTHPC (n = 6). Groups of three animals each were sensitized with 0.15 and 0.5 mg/kg free mTHPC or equimolar dosed pegylated mTHPC followed after 3 days by fluorescence microscopy measurements. RESULTS: Pegylated mTHPC resulted in a similar extent of PDT related tumor necrosis but in lower skin phototoxicity than free mTHPC. Both mTHPC formulations were heterogeneously distributed in the tumor and were mainly localized in perivascular areas. Pegylated mTHPC revealed a higher tumor to skin fluorescence intensity ratio than free mTHPC (P<0.001). CONCLUSIONS: Fluorescence signaling measurement has the potential to predict the photodynamic activity for both mTHPC formulations in mesothelioma xenografts. PMID- 17345625 TI - Laser-assisted straightening of deformed cartilage: numerical model. AB - BACKGROUND AND OBJECTIVES: The potential application of laser cartilage reshaping (LCR) for correction of septal deviations has generated increasing clinical interest, because septoplasty is among the top five most common operations performed. However, few studies have investigated stress fields existing in the nasal septal cartilage during LCR of septal deviations. The objectives of this study were to: (1) formulate a finite-element model describing stress fields in mechanically straightened septal cartilage, (2) calculate stress fields in the septum after a given pattern of laser irradiation produced thermally induced stress relaxation in selected sites, and (3) investigate the dependence of the overall stress relaxation in a straightened septum as a function of the number, location, and size of laser irradiation sites. STUDY DESIGN/MATERIALS AND METHODS: The cartilagenous nasal septum was modeled as 24 x 24 x 2-mm slab. The deviation was represented as a bulge running along the center of the septum with a maximum elevation of 2 mm above the surface. A straightening deformation was represented in form of displacement boundary condition applied to the bulge convex surface with maximum displacement amplitude at center of the septum. Laser irradiation applied in a pattern of one, two, and three lines parallel to the bulge was assumed. The effect of thermally induced stress relaxation was modeled as a simultaneous change in the cartilage mechanical properties and reduction of strain to zero occurring inside the laser heated zone. The finite-element method was used to calculate stress fields within cross-section of the straightened septum and the force of reaction to the straightening deformation before and after laser irradiation. Calculations were performed for the width and depth of thermally modified zones varying from 0.5 to 3 mm and from 0.5 to 2 mm, respectively. Irradiation of convex and concave sides of the deviation was studied. RESULTS: The straightening deformation produced a stress field with both regions of tension and compression present. Maximum stress values were obtained on the surface where the straightening deformation was applied. Reaction force decreased with increasing width and depth of the relaxation zones and depends on location and number of these zones. The maximum reduction of reaction force obtained with three zones (3 mm wide and 2 mm deep) optimally placed in regions of stress concentration was 98%. However, using the same pattern of stress relaxation zones but with a depth of only 1 mm produces a reaction force reaction of 91%. Irradiation of convex side of the deviation reduced reaction force approximately twice as much as irradiation of the concave side. CONCLUSIONS: The present numerical simulation of the stress field in laser-reshaped deviated septum shows highly non-homogeneous stress distributions before and after laser treatment. Using reasonable assumptions on how the mechanical behavior of cartilage changes after heating, the model allows estimation reaction force and its reduction following localized laser irradiation as a function of size and location of laser heated zones. PMID- 17345626 TI - Pulmonary disease is a component of distal arthrogryposis type 5. AB - We report on a three-generation family with distal arthrogryposis type 5 (DA5). The family has four affected members in three generations with an apparent autosomal dominant pattern of inheritance. Three affected individuals were examined. All have distal joint contractures with absent flexion creases, limited mobility of all small and large joints, unusual stance with shortened heel cords and pes cavus, firm muscles, short stature, decreased extraocular movements, and pectus excavatum. The propositus has pulmonary hypertension secondary to chronic hypoxia from restrictive chest disease, alveolar hypoventilation, and residence at 7,000 feet above sea level. Cardiac catheterization documented pulmonary artery pressure of 54 mmHg and a pulmonary capillary wedge pressure of 10 mmHg. Pulmonary function tests showed severe chest restriction (forced vital capacity 30% of predicted; total lung capacity 51% predicted); and reduction of maximal inspiratory and expiratory pressures. Arterial blood gases documented alveolar hypoventilation. Restrictive chest disease is a component of DA5. This implies involvement of the skeletal, and/or respiratory muscles. All individuals diagnosed with DA5 should be evaluated for chest disease, alveolar hypoventilation, as treatment of chronic hypoxia may delay or reverse pulmonary hypertension. PMID- 17345627 TI - Over-expression of BMP4 and BMP5 in a child with axial skeletal malformations and heterotopic ossification: a new syndrome. AB - Bone morphogenetic proteins (BMPs) are a highly conserved class of signaling molecules that induce ectopic cartilage and bone formation in vivo. Dysregulated expression of bone morphogenetic protein 4 (BMP4) is found in the cells of patients who have fibrodysplasia ossificans progressiva (FOP), a genetic disorder of axial and appendicular skeletal malformation and progressive heterotopic ossification. Loss of function mutations in the bone morphogenetic protein 5 (bmp5) gene leading to under-expression of BMP5 cause the murine short ear syndrome, characterized by small malformed ears and a broad range of axial skeletal malformations. We found features reminiscent of both the short ear mouse and FOP in a child with malformed external ears, multiple malformations of the axial skeleton, and progressive heterotopic ossification in the neck and back. We examined BMP mRNA expression in transformed lymphocytes by semi-quantitative RT PCR and protein expression by ELISA assays and immunohistochemistry. Elevated levels of BMP4 and BMP5 mRNA and protein were detected in the patient's cells while levels of BMP2 mRNA were unchanged. Our data suggest that dysregulated expression of BMP4 and BMP5 genes is associated with an array of human axial skeletal abnormalities similar to the short ear mouse and FOP. PMID- 17345628 TI - Health insurance and chronic illness: is anything helping? PMID- 17345629 TI - Nuclear magnetic relaxation dispersion study of the dynamics in solid homopolypeptides. AB - The (1)H nuclear magnetic relaxation dispersion profiles were measured from 10 kHz to 30 MHz as a function of temperature for polyglycine, polyalanine, polyvaline, and polyphenylalanine to examine the contributions of different side chain motions to the polypeptide proton relaxation rate constants. The spin fracton theory for (1)H relaxation is modified to account for high frequency motions of side chains that are dynamically connected to the linear polymer backbone. The (1)H relaxation is dominated by propagation of rare disturbances along the backbone of the polymer. The side-chain dynamics cause an off-set in the field dependence of the (1)H spin-lattice relaxation rate constants which obey a power law in the Larmor frequency in the limit of low and high magnetic field strength. PMID- 17345630 TI - Precise bacterial polyprenol length control fails in Saccharomyces cerevisiae. AB - A comparison of amino acid sequences of yeast Rer2p and Srt1p Z prenyltransferases shows that the spatial organization of their substrate tunnels agrees with that determined by X-ray for the E. coli undecaprenyl diphosphate synthase (UPPs). The observed trend in the maxima of product length distribution shifted from C(55) in UPPs to C(80) in Rer2p and to C(110) in Srt1p. This suggests a significant increase in the size of the enzyme hydrophobic tunnel from approximately 1000 A(3) of E. coli UPPs to approximately 1300 A(3) required to accommodate C(80) in Rer2p and to 1700 A(3) for C(110) in Srt1p. Moreover, Srt1p products reaching C(290) indicate the failure of a strict bacterial-like chain length control. On the basis of E. coli UPPs crystallographic structure the yeast Rer2p model was constructed. In the model three amino acid residues inserted into the sequence corresponding to the "floor" region of the tunnel extends the bottom loop what results in the required increase of the tunnel volume. Moreover, thermal fluctuations of this loop occasionally create a hole in the tunnel floor, making escape of polyprenol omega end out of the tunnel possible what switches off the control mechanism of product length thereby allowing a practically unlimited elongation process leading to an exponential distribution of longer chain polyprenols. PMID- 17345631 TI - Structure, stability, and chaperone function of alphaA-crystallin: role of N terminal region. AB - Small heat shock protein alphaA-crystallin, the major protein of the eye lens, is a molecular chaperone. It consists of a highly conserved central domain flanked by the N-terminal and C-terminal regions. In this article we studied the role of the N-terminal domain in the structure and chaperone function of alphaA crystallin. Using site directed truncation we raised several deletion mutants of alphaA-crystallin and their protein products were expressed in Escherichia coli. Size exclusion chromatography of these purified proteins showed that deletion from the N-terminal beyond the first 20 residues drastically reduced the oligomeric association of alphaA-crystallin and its complete removal resulted in a tetramer. Chaperone activity of alphaA-crystallin, determined by thermal and nonthermal aggregation and refolding assay, decreased with increasing length of deletion and little activity was observed for the tetramer. However it was revealed that N-terminal regions were not responsible for specific recognition of natural substrates and that low affinity substrate binding sites existed in other part of the molecule. The number of exposed hydrophobic sites and the affinity of binding hydrophobic probe bis-ANS as well as protein substrates decreased with N terminal deletion. The stability of the mutant proteins decreased with increase in the length of deletion. The role of thermodynamic stability, oligomeric size, and surface hydrophobicity in chaperone function is discussed. Detailed analysis showed that the most important role of N-terminal region is to control the oligomerization, which is crucial for the stability and in vivo survival of this protein molecule. PMID- 17345632 TI - PFG-NMR diffusometry: a tool for investigating the structure and dynamics of noncommercial purified pig gastric mucin in a wide range of concentrations. AB - For the first time, Pulsed Field Gradient-Nuclear Magnetic Resonance, a powerful noninvasive tool for studying the dynamics and structure of complex gels, has been used to measure diffusion of probe molecules in aqueous solutions/gels of noncommercial purified pig gastric mucin (PGM), in a concentration range up to 5 wt %. Complementary data were obtained from rheology measurements. The combination of techniques revealed a strong pH dependency of the structure of the PGM samples while changes in concentration, ionic strength, and temperature appeared to induce less pronounced alterations. Viscosity was found to vary in a nonmonotonous way with pH, with the more viscous solutions found at intermediate pH. We propose that this finding is due to a reduced charge density at lower pH, which is expected to continuously increase the relative importance of hydrophobic associations. The results suggest a loose network of expanded fully charged PGM molecules with considerable mobility at neutral pH (pH 7.4). At intermediate pH (pH 4), a three-dimensional expanded network is favored. At pH 1, the charge density is low and microphase separation occurs since hydrophobic associations prevail. This leads to the formation of clusters concentrated in PGM molecules separated by regions depleted in PGM. The results obtained increase our knowledge about the gastric mucosal layer, which in vivo contains mucin in the same concentration range as that of the samples investigated here. PMID- 17345633 TI - Time-resolved, high-resolution contrast-enhanced MR angiography of dialysis shunts using the CENTRA keyhole technique with parallel imaging. AB - PURPOSE: To evaluate the use of a dynamic keyhole magnetic resonance angiography (MRA) sequence combined with sensitivity encoding (SENSE) for hemodialysis shunts, because surveillance with conventional contrast-enhanced MRA (CE-MRA) is limited by its low temporal resolution, resulting in arteriovenous overlay. MATERIALS AND METHODS: A total of 12 patients with Brescia-Cimino shunts were investigated prospectively using the new technique. During the contrast passage (gadoterate, Gd-DOTA) a series of five to nine dynamic central k-space measurements (10% for upper-arm shunt, 25% for lower-arm shunt) followed by a full reference data set were acquired. The outer k-space data of the single reference scan were used to complete the dynamic data sets. RESULTS: All studies were diagnostic (17 stenoses, three aneurysms) without complications. The acquisition times for a single dynamic scan of the upper- and lower-arm shunts were 2.2 and 3.2 seconds, respectively, while the reference scan needed 13 and 22.4 seconds, respectively. The dynamic angiograms allowed the differentiation of arterial and venous filling despite a mean peak delay time of only 4.2 seconds in the shoulder region. Image quality qualified in consensus by two experienced readers was rated "good" in 19 cases and "intermediate" in five cases with high mean values for signal-to-noise ratios (SNRs) and contrast-to-noise-ratios (CNRs). CONCLUSION: We have successfully implemented a fast, dynamic, CE-MRA technique with CE timing robust angiography (CENTRA) keyhole and SENSE in clinical routine. High spatial and temporal resolution improve the diagnostics of dialysis shunts and allow the assessment of detailed, dynamic, four-dimensional (4D) information. PMID- 17345634 TI - Differentiation of fibroblastic meningiomas from other benign subtypes using diffusion tensor imaging. AB - PURPOSE: To differentiate fibroblastic meningiomas, usually considered to be of a hard consistency, from other benign subtypes using diffusion tensor imaging (DTI). MATERIALS AND METHODS: From DTI data sets of 30 patients with benign meningiomas, we calculated diffusion tensors and mean diffusivity (MD) and fractional anisotropy (FA) maps as well as barycentric maps representing the geometrical shape of the tensors. The findings were compared to postoperative histology. The study was approved by the local ethics committee, and informed consent was given by the patients. RESULTS: According to one-way analysis of variance (ANOVA), FA was the best parameter to differentiate between the subtypes (F=32.2; p<0.0001). Regarding tensor shape, endothelial meningiomas were represented by spherical tensors (80%) corresponding to isotropic diffusion, whereas the fibroblastic meningiomas showed a high percentage (43%) of nonspherical tensors, indicating planar or longitudinal diffusion. The difference was highly significant (F=28.4; p<0.0001) and may be due to the fascicular arrangement of long spindle-shaped tumor cells and the high content of intra- and interfascicular fibers as shown in the histology. In addition, a capsule-like rim of the in-plane diffusion surrounded most meningiomas irrespective of their histological type. CONCLUSION: If these results correlate to the intraoperative findings of meningioma consistency, DTI-based measurement of FA and analysis of the shape of the diffusion tensor is a promising method to differentiate between fibroblastic and other subtypes of benign meningiomas in order to get information about their "hard" or "soft" consistency prior to removal. PMID- 17345635 TI - Time-resolved 3D MR velocity mapping at 3T: improved navigator-gated assessment of vascular anatomy and blood flow. AB - PURPOSE: To evaluate an improved image acquisition and data-processing strategy for assessing aortic vascular geometry and 3D blood flow at 3T. MATERIALS AND METHODS: In a study with five normal volunteers and seven patients with known aortic pathology, prospectively ECG-gated cine three-dimensional (3D) MR velocity mapping with improved navigator gating, real-time adaptive k-space ordering and dynamic adjustment of the navigator acceptance criteria was performed. In addition to morphological information and three-directional blood flow velocities, phase-contrast (PC)-MRA images were derived from the same data set, which permitted 3D isosurface rendering of vascular boundaries in combination with visualization of blood-flow patterns. RESULTS: Analysis of navigator performance and image quality revealed improved scan efficiencies of 63.6%+/ 10.5% and temporal resolution (<50 msec) compared to previous implementations. Semiquantitative evaluation of image quality by three independent observers demonstrated excellent general image appearance with moderate blurring and minor ghosting artifacts. Results from volunteer and patient examinations illustrate the potential of the improved image acquisition and data-processing strategy for identifying normal and pathological blood-flow characteristics. CONCLUSION: Navigator-gated time-resolved 3D MR velocity mapping at 3T in combination with advanced data processing is a powerful tool for performing detailed assessments of global and local blood-flow characteristics in the aorta to describe or exclude vascular alterations. PMID- 17345636 TI - MR compatibility of EEG scalp electrodes at 4 tesla. AB - PURPOSE: To design and apply a method to quantitatively evaluate the MR compatibility of electroencephalographic (EEG) scalp electrodes based on pulse sequence-independent metrics. MATERIALS AND METHODS: Three types of electrodes (constructed primarily of brass, silver, and conductive plastic, respectively) were tested. B0 field distortions, B1 shielding, and heat induction was measured in adjacent agarose and oil phantoms at 4 T. B0 field maps were corrected for distortions caused by the measurement apparatus and passive shim heating, and projections perpendicular to the surfaces of the electrodes were fit, generating cubic coefficients representing the electrode distortion severity. Signal loss in T2-weighted images was used to determine B1 shielding by the electrodes. Temperature measurements were recorded during the application of a high-power pulse sequence. RESULTS: Significantly different B0 distortions were observed in the three types of electrodes. The B1 shielding detected in all three electrodes is minimal for most human MRI, and no significant heating was detected in the electrodes or adjacent phantom. CONCLUSION: The three types of electrodes were successfully differentiated in terms of MR compatibility based on pulse sequence independent B0 field distortions. PMID- 17345637 TI - Submillimeter isotropic resolution carotid wall MRI with swallowing compensation: imaging results and semiautomated wall morphometry. AB - PURPOSE: To assess a swallowing-compensated, three-dimensional (3D) diffusion prepared segmented steady-state free precession (3D Nav-D-SSFP) technique for carotid wall MRI with 0.6-mm isotropic spatial resolution, and its utility for semiautomated carotid wall morphometry. MATERIALS AND METHODS: The carotid arteries of seven healthy volunteers (N=14) were imaged with 3D Nav-D-SSFP and black-blood T2-weighted (T2w) two-dimensional (2D) fast spin-echo (FSE). Carotid wall-lumen contrast-to-noise ratio (CNR) was measured with both sequences. Measurement of carotid wall area (WA) and lumen area (LA) made in a semiautomated manner off of the 3D Nav-D-SSFP images were compared to those made manually. RESULTS: Adjusted for voxel volume and number of slices, a near six-fold improvement in CNR per unit time was achieved with 3D Nav-D-SSFP relative to 2D T2w FSE (P<0.001). Manual and semiautomated measurements of carotid WA and LA on the 3D Nav-D-SSFP images were highly correlated (intraclass correlation coefficient (ICC)=0.961 and 0.996, respectively; P<0.001). CONCLUSION: 3D Nav-D SSFP is a time-efficient, swallowing-compensated, black-blood technique that lends itself for semiautomated measurements of carotid WA and LA that are in good agreement with manual measurements. PMID- 17345639 TI - Ultrastructural observations of previtellogenic ovarian follicles of the caecilians Ichthyophis tricolor and Gegeneophis ramaswamii. AB - The ultrastructural organization of the previtellogenic follicles of the caecilians Ichthyophis tricolor and Gegeneophis ramaswamii, of the Western Ghats of India, were observed. Both species follow a similar seasonal reproductive pattern. The ovaries contain primordial follicles throughout the year with previtellogenic, vitellogenic, or postvitellogenic follicles, depending upon the reproductive status. The just-recruited primordial follicle includes an oocyte surrounded by a single layer of follicle and thecal cells. The differentiation of the theca into externa and interna layers, the follicle cells into dark and light variants, and the appearance of primordial yolk platelets and mitochondrial clouds in the ooplasm mark the transition of the primordial follicle into a previtellogenic follicle. During further development of the previtellogenic follicle the following changes occur: i) the theca loses distinction as externa and interna; ii) all the follicle cells become the dark variant and increase in the complexity of ultrastructural organization; iii) the nucleus of the oocyte transforms into the germinal vesicle and there is amplification of the nucleoli; iv) the primordial yolk platelets of the cortical cytoplasm of the oocyte increase in abundance; v) the mitochondrial clouds fragment and the mitochondria move away from the clouds, leaving behind the cementing matrix, which contains membrane-bound vesicles of various sizes, either empty or filled with a lipid material; vi) the perivitelline space appears first as troughs at the junctional points between the follicle cells and oocyte, which subsequently spread all around to become continuous; vii) macrovilli and microvilli develop from the follicle cells and oocyte, respectively; and viii) the precursor material of the vitelline envelop arrives at the perivitelline space. The sequential changes in the previtellogenic follicles of two species of caecilians are described. PMID- 17345640 TI - A dendrimer-based nanosized contrast agent dual-labeled for magnetic resonance and optical fluorescence imaging to localize the sentinel lymph node in mice. AB - PURPOSE: To preoperatively and intraoperatively localize the sentinel lymph node (SLN), a single hybrid probe for MR and near infrared (NIR) optical imaging was synthesized and tested. MATERIALS AND METHODS: A macromolecular MR/NIR optical contrast agent was synthesized based on a approximately 191 gadolinium-labeled contrast agent using generation-6 polyamidoamine dendrimer (G6), which is also labeled with 2 Cy5.5, an NIR fluorophore. After establishing the optimal dose, the agent was injected into mammary glands of 10 normal mice to examine the lymphatic drainage from the breast using a 3T clinical scanner. Immediately after the MRI scan, NIR optical imaging and image-guided surgery were performed to compare the two imaging modalities. RESULTS: To consistently identify the SLNs, we needed to inject 25 microL of 30 mM [Gd] G6-Cy5.5. All SLNs could be easily identified and resected under NIR optical imaging-guided surgery. Although external NIR optical imaging failed to identify SLNs close to the injection site due to shinethrough, MR lymphography (MRL) consistently identified all SLNs regardless of their location. CONCLUSION: We have successfully synthesized and tested a dual labeled MR/NIR optical hybrid contrast agent, G6-Cy5.5 for reoperative and intraoperative localization of SLNs. PMID- 17345638 TI - Race and ethnicity in genetic research. AB - Use of race and ethnicity terms in genetic research continues to generate controversy. Despite differing opinions about their basis or relevance, there is some agreement that investigators using these terms should: explain why the terms or categories were used, define them carefully, and apply them consistently. An important question is whether these recommendations are reflected in practice. Here we addressed this question based on 330 randomly selected articles published between 2001 and 2004 that reported on genetic research and used one or more words from a defined list of race, ethnicity, or population terms. The recommendation that authors using race or ethnicity terms explain the basis for assigning them to study populations was met infrequently (9.1%), and articles that used race and ethnicity as variables were no more likely than those that used them only to label a sample to provide these details. No article defined or discussed the concepts of race or ethnicity. With limited exceptions, current practice does not reflect repeated recommendations for using race or ethnicity terms in genetic research. This study provides a baseline against which to measure future trends. PMID- 17345641 TI - Distinction of reactive joint fluid from pyogenic abscess by diffusion-weighted imaging. AB - It is difficult to distinguish reactive joint fluid from infectious joint fluid by conventional MR images. In this presented case, we successfully distinguished these two conditions using diffusion-weighted imaging. PMID- 17345642 TI - Effect of bolus length of intraarterial injections on contrast-enhanced MR angiography in patients. AB - PURPOSE: To perform MR-guided interventions, repetitive injections of contrast agent in the arterial system are necessary. By reducing the intraarterial bolus length during image acquisition and consecutively reducing the gadolinium-chelate based contrast agent dose, we focus on a comparable vascular depiction. The tradeoff in reducing bolus length is vascular depiction. MATERIALS AND METHODS: Intraarterial gadolinium-chelate injection was performed to depict the femoropopliteal artery and infrapopliteal arteries in six patients. Six measurements with a bolus length of 20% to 100% of the total acquisition time were performed (three-dimensional [3D] Turbo-fast low-angle shot (FLASH) sequence, 1.5 T). Contrast-to-noise ratio (CNR) was determined and a consensus reading of vascular depiction was performed. RESULTS: CNR values comparable 100% of bolus length were obtained for the femoropopliteal artery at >or=40% and for the infrapopliteal arteries at >or=60%. Qualitative analysis demonstrated that a bolus length of >or=60% is necessary to reveal a good diagnostic vascular depiction. CONCLUSION: Quantitatively, a reduction of intraarterial gadolinium chelate dosage in patients is possible down to 40% in the femoropopliteal artery and to 60% in the infrapopliteal arteries to acquire a CNR comparable to 100% of bolus length. Qualitatively, however, the bolus length can only be reduced down to 60% for both level to produce a good diagnostic vascular depiction and is, for diagnostic purposes, the limiting factor. PMID- 17345643 TI - FBN2, FBN1, TGFBR1, and TGFBR2 analyses in congenital contractural arachnodactyly. AB - FBN2, FBN1, TGFBR1, and TGFBR2 were analyzed by direct sequencing in 15 probands with suspected congenital contractural arachnodactyly (CCA). A total of four novel FBN2 mutations were found in four probands (27%, 4/15), but remaining the 11 did not show any abnormality in either of the genes. This study indicated that FBN2 mutations were major abnormality in CCA, and TGFBR and FBN1 defects may not be responsible for the disorder. FBN2 mutations were only found at introns 30, 31, and 35 in this study. Thus analysis of a mutational hotspot from exons 22 to 36 (a middle part) of FBN2 should be prioritized in CCA as previously suggested. PMID- 17345644 TI - The consistency of combat exposure reporting and course of PTSD in Vietnam War veterans. AB - Self-reports of traumatic events are often used in clinical and epidemiologic studies. Nevertheless, research suggests combat exposure reports may be biased by posttraumatic stress disorder (PTSD) symptom severity, leading to an inflated dose-response relation between combat exposure and PTSD. The authors examined the consistency in combat exposure reports and their relation to PTSD symptoms in Vietnam Veteran American Legionnaires who responded to two mailed surveys (1984, 1998; N = 1,462). Combat exposure reports were highly reliable (test-retest correlation = 0.87). However, changes in exposure reporting were related to changes in PTSD symptoms, specifically reexperiencing symptoms. The effect size of the dose-response relation attributable to changes in reporting was smaller for continuous than categorical measures. Findings are discussed in relation to recent controversies over veterans' combat exposure reports. PMID- 17345645 TI - Risk and resilience factors for posttraumatic stress symptomatology in Gulf War I veterans. AB - What factors distinguish war-exposed veterans who experience posttraumatic stress symptomatology (PTSS) from those who do not? This study used structural equation modeling procedures to examine the complex interplay among predeployment, war zone, and postdeployment factors as they relate to PTSS in a sample of Gulf War I veterans. A primary goal was to determine to what extent previously documented associations among Vietnam veterans would replicate in this more contemporary veteran cohort. Results supported a multivariate etiological perspective on PTSS, with war-zone factors accounting for the largest proportion of variance in PTSS. The majority of hypothesized associations held, suggesting that the mechanisms underlying PTSS may be similar across veteran cohorts. PMID- 17345646 TI - Primary skeletal muscle involvement in chorea-acanthocytosis. AB - Chorea-acanthocytosis (ChAc) is a hereditary disease characterized by involuntary movements and amyotrophy with elevation of serum creatine kinase. Although skeletal muscle involvement in ChAc has been suggested, the mechanism remains unclear. To investigate chorein abnormalities of the skeletal muscles of ChAc patients with an apparently heterozygous VPS13A mutation compared with those of other hereditary choreic diseases, we performed histological and immunohistochemical studies of the skeletal muscles from 3 ChAc, 1 Huntington's disease (HD), 1 McLeod syndrome (MLS), and 1 normal control (NC) with 2 originally generated anti-chorein antibodies. Chorein immunoreactivities in HD, MLS, and NC were found linearly along the sarcolemma and appeared as speckles in the sarcoplasma, but those in ChAc were uneven and discontinuous along the sarcolemmas and increased in the sarcoplasma especially in type I fibers. This histological observation suggests chorein abnormalities of skeletal muscles might be associated with primary involvement of skeletal muscles in this disorder. PMID- 17345647 TI - Intergenerational transmission of trauma: exploring mother-infant prenatal attachment. AB - Early childhood attachment and bonding and the intergenerational transmission of trauma are two key areas to address to understand the connection between parental trauma and the parent-child relationship. The purpose of the current study was to explore the relationship between trauma and past parental attachment behaviors of 41 expectant mothers and the subsequent development of attachment and bonding with their unborn child. Results of the current study suggest that trauma history, in general, does not negatively impact expectant mothers' current prenatal attachment with their unborn child. However, interpersonal trauma history does appear to have negative effects on prenatal attachment. These results point to the importance of understanding the role of interpersonal trauma exposure on prenatal attachment. PMID- 17345648 TI - The effects of childhood trauma on daily mood lability and comorbid psychopathology in bulimia nervosa. AB - A study of bulimic women examined the relationship between histories of childhood trauma and psychiatric disorders, as well as daily measures of mood and behavior. One hundred twenty-three women with bulimia nervosa were assessed with interviews and completed an Ecological Momentary Assessment (EMA) protocol in which they carried a palmtop computer for 2 weeks. Sexual abuse was associated with a history of mood and anxiety disorders, and emotional abuse with eating disorder psychopathology. In the EMA assessment, sexual abuse was associated with daily purging frequency and self-destructive behavior. Emotional abuse was associated with average daily mood and mood lability. These findings support the idea that child maltreatment may be associated with various aspects of bulimia-related psychopathology. PMID- 17345649 TI - Intimate partner psychological aggression and child behavior problems. AB - The present study examined the relationship between intimate partner psychological aggression and children's behavior problems in a community sample of families (N = 470 children). The results showed that psychological aggression experienced by the mother has adverse effects on children's externalizing and internalizing behavior problems over and above the effects of physical aggression. The association between psychological aggression and child behavior problems was partially mediated by maternal distress. Exposure to psychological aggression appears to have unique direct and indirect adverse effects on children. PMID- 17345650 TI - Use of mental health treatment among veterans filing claims for posttraumatic stress disorder. AB - This study examines predictors of current mental health service use in a sample of 154 veterans filing claims for Veterans Affairs (VA) disability benefits based on Posttraumatic Stress Disorder (PTSD). Our conceptual framework was the behavioral model that classifies predictors of service utilization into predisposing (background), enabling (e.g., insurance) and need (e.g., symptoms) factors. Slightly more than half of the PTSD claimants were receiving mental health treatment at the time of claim initiation. Mean symptom levels were clinically significant in both users and nonusers of mental health treatment. In a multivariate logistic regression analysis, mental health treatment use was associated with younger age, marriage, and dependence on public insurance. Implications for future research are discussed. PMID- 17345651 TI - Factors affecting burnout and compassion fatigue in psychotherapists treating torture survivors: is the therapist's attitude to working through trauma relevant? AB - In this study, a group of trauma therapists (N = 100) working with torture survivors was investigated with respect to the extent to which they advocated and practiced working through traumatic events as well as levels of symptomatology including compassion fatigue, burnout, and distress. Results showed that a combination of high advocacy and low degree of working through traumatic events was related to high symptomatology. Therapists with this combination showed more compassion fatigue, burnout, and distress than therapists who advocated and practiced working through traumatic events, as well as therapists who neither advocated nor practiced it. Results are discussed with respect to the pathogenic role of fear avoidance in therapists. PMID- 17345653 TI - Ailing healthcare in India. PMID- 17345654 TI - [Health institutions and power in Latin America]. PMID- 17345655 TI - [Historical sketch of state medicine in Central America]. AB - This essay sketches the fundamental characteristics of state medicine and public health in Central America, with an emphasis on the 20th century. The picture is variable, given the distinct configurations of political regime, ethnic division, and social conflict, some of them quite extreme. A high degree of historical continuity is noted in the way these factors have influenced the formation or deformation of public health and state medicine systems. Although external agents have had a strong presence in the health sector of most Central American countries, the paper argues that the historical forces that determine the nature of state medical systems in the isthmus are internal rather than external. Despite the historically weak development of state medicine in most countries, the question of public access to medicine has played an important and often highly charged role in the political life of most Central American countries. PMID- 17345656 TI - [The shaping of the Argentina health system: the case of Cordoba province, 1917 1926]. AB - This article describes the construction of the health system in Cordoba province between the end of the 19th century and the second half of the 1920s, placing particular emphasis in the national institutions and private charity associations created during this period. The hypothesis of this article is that the Cordoba health system was developed from the initiative of private charity associations and at the level of the nation or municipality, whereas the provincial state had a limited role. These developments occurred despite the hegemony of a liberal discourse that reinforced the role of the state as the main agent in public health care. PMID- 17345657 TI - [Health dictatorship, education and hygiene promotion in Revolutionary Mexico, 1917-1934]. AB - This work aims to study the so-called Mexican "health dictatorship", whose legal basis was established with the promulgation of the Political Constitution in 1917, but which maintained itself more as a discourse than as a practice. Instead of authoritarian politics, hygiene education and promotion were used as means of "regenerating" the Mexican people and leading the nation along the path of progress and civilization. This paper intends to show the importance given to hygiene campaign between 1917 and 1934 by the regime that emerged from the Mexican Revolution (1910-1917). PMID- 17345658 TI - [Public health and power in Mexico during Cardenism: 1934-1940]. AB - Historians have identified three stages in the government of Lazaro Cardenas (1934-1940): consolidation of the power of Cardenas; a nationalist and reformist policy (including agrarian reform and nationalisation of the railway system and oil industry); and withdrawal of the reforms due to the reaction of conservative sectors and imperialist countries. This article attempts to reveal the impact of each stage on the Mexican public health system and to demonstrate that the first systematic attempt to establish permanent rural health units was developed during this period. PMID- 17345659 TI - [Images of public health: the institutionalisation of the Instituto Oswaldo Cruz in Brazil]. AB - In this article, the authors uncover the key role of photographic activity in the institutionalizing and validating of the Instituto Oswaldo Cruz (IOC) during the first half of the twentieth century. Photographic images not only increasingly accompanied their scientific work, but also became a central tool for promoting the activities of the IOC. The images included in this article reveal the importance of photographic activity in the institutional construction of the IOC. PMID- 17345660 TI - [Political changes and public health reforms in Brazil. The first Vargas government (1930-1945)]. AB - The goal of this article is to describe and analyze the institutional and public health policy changes produced in Brazil during the government of Getulio Vargas between 1930 and 1945. This article intends to cover a regrettable historiographical void regarding public health policies during this crucial period of 20th century Brazilian history. A key tissue of this article is the relation established between the public health reforms and the political and ideological changes that occurred under the political regime installed in 1930, signalling both the transformations and the continuities with past regimes and the impact of these transformations in the contemporary Brazilian public health system. PMID- 17345661 TI - [Expansion of state authority and the Special Public Health Service in Brazil, 1942-1960]. AB - The Special Public Health Service (Servicio Especial de Salud Publica-SESP) was created in 1942 as a bilateral agency between Brazil and the United States, thanks to an agreement signed by the Brazilian Ministry of Education and Health and the Institute for Inter-American Affairs. Although it was originally conceived by the Americans as a temporary agency with the military purposes of "cleaning the Amazon" and stimulating rubber production, the SESP contributed from its beginningS to an expansion of the presence of the Brazilian state. In the context of the "Cold War" and the "discovery of underdevelopment", the SESP reoriented its goals towards the formation of a district model of healthcare, based on the construction of a horizontal and permanent network of sanitary units. Despite its international constitution and its inspiration on a American model, the health policies of the SESP in Brazil never resulted from a one-way process. On the contrary, they were the result of a process of conflict, negotiation, resistance and adaptation. The combination of American influences and local responses shaped the history of the SESP in Brazil. PMID- 17345662 TI - [Change and revolution: the rise of the National Health System in Cuba, 1959 1970]. AB - This article studies the impact on the Cuban public health system of the political, economical and social changes that occurred after the 1959 Revolution, and the main transformations that occurred in the Cuban public health system during the 1960s, such as the creation of a new public health ministry, the nationalization of the pharmaceutical industry, the massive emigration of health professionals, a reform of medical studies, the creation of a Medical Rural Service, the incorporation of socialist principles in public health and the development of primary health care. As this article intends to demonstrate, these measures guided Cuban public health reform towards the construction of a state monopolized National Health System in 1970. PMID- 17345663 TI - [Desperately seeking decentralisation: Mexican health policies in two periods of reform: the 1920s-30s and the 1980s]. AB - This article compares public health policy reforms in Mexico during the 1920s and 1930s with subsequent reforms initiated in the 1980s. The attempts at decentralization in the 1920s-30s were supported by the Rockefeller Foundation, which was interested in the formation of local cooperative health units. In the 1980s, the aim of the Mexican government and international financial agencies, such as the Inter-American Development Bank, was to reduce public spending (as part of "structural adjustment" policies). One of the hypotheses of this article is that, in the end, the public health reforms were unable to overcome the limitations imposed by Mexico's political centralization and longstanding inequities in public spending. At the same time, one of the unforeseen achievements of these reforms was an increase in local capabilities to demand a better distribution of social services. PMID- 17345664 TI - [Effects of arsenic trioxide on the autoimmunity and survival time in BXSB lupus mice]. AB - OBJECTIVE: To investigate the effect of arsenic trioxide (ATO) on the autoimmunity and survival time in BXSB lupus mice. METHODS: The model BXSB lupus mice were randomly divided into two groups equally, the ATO treated group and the control group, 17 in each group. Mice in the ATO group were given intraperitoneal injection of ATO at the daily dose of 0.4 mg/kg, once every other day for 105 days or 90 days, respectively, and the observation lasted for 210 days. The survival time between the two groups was compared; the serum levels of anti-dsDNA and IgG were detected by enzyme-linked immunosorbent assay (ELISA), and the interferon-gamma (IFN-gamma) mRNA expression in renal and spleen tissue were measured by reverse transcriptase polymerase chain reaction (RT-PCR) technique. RESULTS: Till the 210th day, the total number of death was 8 in the ATO treated group and 13 in the control group, comparison between the two groups showed significantly different (chi2 = 4.20, P < 0.05). The mean OD value of serum anti dsDNA antibody was lower in the ATO group (0.392 +/- 0.087) than that in the control group (0.566 +/- 0.080, P < 0.001). The serum level of IgG on day 105 in the ATO group was significantly lower than that in the control group and before treatment (P < 0.05). The expression of IFN-gamma mRNA in spleen tissue and renal tissue in the ATO group and the control group was 0.540 +/- 0.300 and 0.338 +/- 0.163, 2.320 +/- 0.522 and 0.588 +/- 0.104 (P < 0.05 and P < 0.01 respectively). CONCLUSION: ATO can prolong the survival time of BXSB lupus mice, decrease the peripheral level of anti-dsDNA antibody and IgG expression, inhibit the over expression of IFN-gamma mRNA in spleen and kidney tissues. PMID- 17345665 TI - Palestinians: the crisis in medical care. PMID- 17345667 TI - Abstracts of the NAASO, The Obesity Society Annual Meeting, October 20-24, 2006, Boston, Massachusetts, USA. PMID- 17345666 TI - How to inherit IQ: an exchange. PMID- 17345668 TI - Phthisical insanity. PMID- 17345669 TI - Exploring frontiers in the DNA landscape: an introduction to the symposium "Genome Analysis and the Molecular Systematics of Retroelements". AB - The emerging field of phylogenomics is influencing both the amount and type of characters being brought to bear on long-standing problems in systematic biology. Moreover, the proliferation of sequence information from genome projects in concert with the development of new informatics tools is widening access to comparative data on retroelements to a broad cross section of investigators. Motivated by this, the Society of Systematic Biologists sponsored a symposium entitled "Genome Analysis and the Molecular Systematics of Retroelements," and the resulting papers illustrate this theme of new discoveries and cover three basic areas of research: (i) the taxonomic distribution and phylogenetic structure of families of retroelements; (II) the use of SINE and LINE insertions for phylogenetic inference; and (III) the informatics and classification of repetitive elements. Contributions of each article are briefly discussed in this context and particularly fruitful directions for future research illuminated by results of this symposium are reviewed. PMID- 17345670 TI - Distribution and phylogeny of Penelope-like elements in eukaryotes. AB - Penelope-like elements (PLEs) are a relatively little studied class of eukaryotic retroelements, distinguished by the presence of the GIY-YIG endonuclease domain, the ability of some representatives to retain introns, and the similarity of PLE encoded reverse transcriptases to telomerases. Although these retrotransposons are abundant in many animal genomes, the reverse transcriptase moiety can also be found in several protists, fungi, and plants, indicating its ancient origin. A comprehensive phylogenetic analysis of PLEs was conducted, based on extended sequence alignments and a considerably expanded data set. PLEs exhibit the pattern of evolution similar to that of non-LTR retrotransposons, which form deep branching clades dating back to the Precambrian era. However, PLEs seem to have experienced a much higher degree of lineage losses than non-LTR retrotransposons. It is suggested that PLEs and non-LTR retrotransposons are included into a larger eTPRT (eukaryotic target-primed) group of retroelements, characterized by 5' truncation, variable target-site duplication, and the potential of the 3' end to participate in formation of non-autonomous derivatives. PMID- 17345671 TI - Phylogenomic analysis of the L1 retrotransposons in Deuterostomia. AB - L1 retrotransposons constitute the largest single component of mammalian genomes. In contrast to the single remaining lineage of L1 retrotransposons in mammalian genomes, some teleost fishes contain a highly diverse L1 retrotransposon repertoire. Major evolutionary changes in L1 retrotransposon repertoires have therefore taken place in the land vertebrates (Tetrapoda). The lack of sequence data for L1 retrotransposons in the basal living Tetrapoda lineages prompted an investigation of their distribution and evolution in the genomes of the key tetrapod lineages, amphibians and reptiles, and in lungfishes. In this study, we combined genome database searches with PCR analysis to demonstrate that L1 retrotransposons are present in the genomes of lungfishes, amphibians, and lepidosaurs. Phylogenomic analysis shows that the genomes of Deuterostomia possess three highly divergent groups of L1 retrotransposons, with distinct distribution patterns. The analysis of L1 diversity shows the presence of a very large number of diverse L1 families, each with very low copy numbers, at the time of the origin of tetrapods. During the evolution of synapsids, all but one L1 lineage have been lost. This study establishes that the loss of L1 diversity and explosion in copy numbers occurred in the synapsid ancestors of mammals, and was most probably caused by severe population bottlenecks. PMID- 17345672 TI - Phylogenomic investigation of CR1 LINE diversity in reptiles. AB - It is unlikely that taxonomically diverse phylogenetic studies will be completed rapidly in the near future for nonmodel organisms on a whole-genome basis. However, one approach to advancing the field of "phylogenomics" is to estimate the structure of poorly known genomes by mining libraries of clones from suites of taxa, rather than from single species. The present analysis adopts this approach by taking advantage of megabase-scale end-sequence scanning of reptilian genomic clones to characterize diversity of CR1-like LINEs, the dominant family of transposable elements (TEs) in the sister group of mammals. As such, it helps close an important gap in the literature on the molecular systematics and evolution of retroelements in nonavian reptiles. Results from aligning more than 14 Mb of sequence from the American alligator (Alligator mississippiensis), painted turtle (Chrysemys picta), Bahamian green anole (Anolis smaragdinus), Tuatara (Sphenodon punctatus), Emu (Dromaius novaehollandiae), and Zebra Finch (Taeniopygia guttata) against a comprehensive library approximately 3000 TE encoding peptides reflect an increasing abundance of LINE and non-long-terminal repeat (non-LTR) retrotransposon repeat types with the age of common ancestry among exemplar reptilian clades. The hypothesis that repeat diversity is correlated with basal metabolic rate was tested using comparative methods and a significant nonlinear relationship was indicated. This analysis suggests that the age of divergence between an exemplary clade and its sister group as well as metabolic correlates should be considered in addition to genome size in explaining patterns of retroelement diversity. The first phylogenetic analysis of the largely unexplored chicken repeat 1 (CR1) 3' reverse transcriptase (RT) conserved domains 8 and 9 in nonavian reptiles reveals a pattern of multiple lineages with variable branch lengths, suggesting presence of both old and young elements and the existence of several distinct well-supported clades not apparent from previous characterization of CR1 subfamily structure in birds and the turtle. This mode of CR1 evolution contrasts with historical patterns of LINE 1 diversification in mammals and hints toward the existence of a rich but still largely unexplored diversity of nonavian retroelements of importance to advancing both comparative vertebrate genomics and amniote systematics. PMID- 17345673 TI - Extensive morphological convergence and rapid radiation in the evolutionary history of the family Geoemydidae (old world pond turtles) revealed by SINE insertion analysis. AB - The family Geoemydidae is one of three in the superfamily Testudinoidea and is the most diversified family of extant turtle species. The phylogenetic relationships in this family and among related families have been vigorously investigated from both morphological and molecular viewpoints. The evolutionary history of Geoemydidae, however, remains controversial. Therefore, to elucidate the phylogenetic relationships of Geoemydidae and related species, we applied the SINE insertion method to investigate 49 informative SINE loci in 28 species. We detected four major evolutionary lineages (Testudinidae, Batagur group, Siebenrockiella group, and Geoemyda group) in the clade Testuguria (a clade of Geoemydidae + Testudinidae). All five specimens of Testudinidae form a monophyletic clade. The Batagur group comprises five batagurines. The Siebenrockiella group has one species, Siebenrockiella crassicollis. The Geoemyda group comprises 15 geoemydines (including three former batagurines, Mauremys reevesii, Mauremys sinensis, and Heosemys annandalii). Among these four groups, the SINE insertion patterns were inconsistent at four loci, suggesting that an ancestral species of Testuguria radiated and rapidly diverged into the four lineages during the initial stage of its evolution. Furthermore, within the Geoemyda group we identified three evolutionary lineages, namely Mauremys, Cuora, and Heosemys. The Heosemys lineage comprises Heosemys, Sacalia, Notochelys, and Melanochelys species, and its monophyly is a novel assemblage in Geoemydidae. Our SINE phylogenetic tree demonstrates extensive convergent morphological evolution between the Batagur group and the three species of the Geoemyda group, M. reevesii, M. sinensis, and H. annandalii. PMID- 17345674 TI - SINEs of a nearly perfect character. AB - Mobile elements have been recognized as powerful tools for phylogenetic and population-level analyses. However, issues regarding potential sources of homoplasy and other misleading events have been raised. We have collected available data for all phylogenetic and population level studies of primates utilizing Alu insertion data and examined them for potentially homoplasious and other misleading events. Very low levels of each potential confounding factor in a phylogenetic or population analysis (i.e., lineage sorting, parallel insertions, and precise excision) were found. Although taxa known to be subject to high levels of these types of events may indeed be subject to problems when using SINE analysis, we propose that most taxa will respond as the order Primates has--by the resolution of several long-standing problems observed using sequence based methods. PMID- 17345675 TI - Automated scanning for phylogenetically informative transposed elements in rodents. AB - Transposed elements constitute an attractive, useful source of phylogenetic markers to elucidate the evolutionary history of their hosts. Frequent and successive amplifications over evolutionary time are important requirements for utilizing their presence or absence as landmarks of evolution. Although transposed elements are well distributed in rodent taxa, the generally high degree of genomic sequence divergence among species complicates our access to presence/absence data. With this in mind we developed a novel, high-throughput computational strategy, called CPAL (Conserved Presence/Absence Locus-finder), to identify genome-wide distributed, phylogenetically informative transposed elements flanked by highly conserved regions. From a total of 232 extracted chromosomal mouse loci we randomly selected 14 of these plus 2 others from previous test screens and attempted to amplify them via PCR in representative rodent species. All loci were amplifiable and ultimately contributed 31 phylogenetically informative markers distributed throughout the major groups of Rodentia. PMID- 17345676 TI - Short interspersed elements (SINEs) in plants: origin, classification, and use as phylogenetic markers. AB - Short interspersed elements (SINEs) are a class of dispersed mobile sequences that use RNA as an intermediate in an amplification process called retroposition. The presence-absence of a SINE at a given locus has been used as a meaningful classification criterion to evaluate phylogenetic relations among species. We review here recent developments in the characterisation of plant SINEs and their use as molecular makers to retrace phylogenetic relations among wild and cultivated Oryza and Brassica species. In Brassicaceae, further use of SINE markers is limited by our partial knowledge of endogenous SINE families (their origin and evolution histories) and by the absence of a clear classification. To solve this problem, phylogenetic relations among all known Brassicaceae SINEs were analyzed and a new classification, grouping SINEs in 15 different families, is proposed. The relative age and size of each Brassicaceae SINE family was evaluated and new phylogenetically supported subfamilies were described. We also present evidence suggesting that new potentially active SINEs recently emerged in Brassica oleracea from the shuffling of preexisting SINE portions. Finally, the comparative evolution history of SINE families present in Arabidopsis thaliana and Brassica oleracea revealed that SINEs were in general more active in the Brassica lineage. The importance of these new data for the use of Brassicaceae SINEs as molecular markers in future applications is discussed. PMID- 17345677 TI - Mapping uncertainty and phylogenetic uncertainty in ancestral character state reconstruction: an example in the moss genus Brachytheciastrum. AB - The evolution of species traits along a phylogeny can be examined through an increasing number of possible, but not necessarily complementary, approaches. In this paper, we assess whether deriving ancestral states of discrete morphological characters from a model whose parameters are (i) optimized by ML on a most likely tree; (II) optimized by ML onto each of a Bayesian sample of trees; and (III) sampled by a MCMC visiting the space of a Bayesian sample of trees affects the reconstruction of ancestral states in the moss genus Brachytheciastrum. In the first two methods, the choice of a single- or two-rate model and of a genetic distance (wherein branch lengths are used to determine the probabilities of change) or speciational (wherein changes are only driven by speciation events) model based upon a likelihood-ratio test strongly depended on the sampled trees. Despite these differences in model selection, reconstructions of ancestral character states were strongly correlated to each others across nodes, often at r > 0.9, for all the characters. The Bayesian approach of ancestral character state reconstruction offers, however, a series of advantages over the single-tree approach or the ML model optimization on a Bayesian sample of trees because it does not involve restricting model parameters prior to reconstructing ancestral states, but rather allows a range of model parameters and ancestral character states to be sampled according to their posterior probabilities. From the distribution of the latter, conclusions on trait evolution can be made in a more satisfactorily way than when a substantial part of the uncertainty of the results is obscured by the focus on a single set of model parameters and associated ancestral states. The reconstructions of ancestral character states in Brachytheciastrum reveal rampant parallel morphological evolution. Most species previously described based on phenetic grounds are thus resolved of polyphyletic origin. Species polyphylly has been increasingly reported among mosses, raising severe reservations regarding current species definition. PMID- 17345678 TI - Nematode small subunit phylogeny correlates with alignment parameters. AB - The number of nuclear small subunit (SSU) ribosomal RNA (rRNA) sequences for Nematoda has increased dramatically in recent years, and although their use in constructing phylogenies has also increased, relatively little attention has been given to their alignment. Here we examined the sensitivity of the nematode SSU data set to different alignment parameters and to the removal of alignment ambiguous regions. Ten alignments were created with CLUSTAL W using different sets of alignment parameters (10 full alignments), and each alignment was examined by eye and alignment ambiguous regions were removed (creating 10 reduced alignments). These alignment ambiguous regions were analyzed as a third type of data set, culled alignments. Maximum parsimony, neighbor-joining, and parsimony bootstrap analyses were performed. The resulting phylogenies were compared to each other by the symmetric difference distance tree comparison metric (SymD). The correlation of the phylogenies with the alignment parameters was tested by comparing matrices from SymD with corresponding matrices of Manhattan distances representing the alignment parameters. Differences among individual parsimony trees from the full alignments were frequently correlated with the differences among alignment parameters (580/1000 tests), as were trees from the culled alignments (403/1000 tests). Differences among individual parsimony trees from the reduced alignments were less frequently correlated with the differences among alignment parameters (230/1000 tests). Differences among majority-rule consensus trees (50%) from the parsimony analysis of the full alignments were significantly correlated with the differences among alignment parameters, whereas consensus trees from the reduced and culled analyses were not correlated with the alignment parameters. These patterns of correlation confirm that choice of alignment parameters has the potential to bias the resultant phylogenies for the nematode SSU data set, and suggest that the removal of alignment ambiguous regions reduces this effect. Finally, we discuss the implications of conservative phylogenetic hypotheses for Nematoda produced by exploring alignment space and removing alignment ambiguous regions for SSU rDNA. PMID- 17345679 TI - Accurate branch length estimation in partitioned Bayesian analyses requires accommodation of among-partition rate variation and attention to branch length priors. PMID- 17345680 TI - Why U.S. health care costs aren't too high. PMID- 17345681 TI - How Managers' everyday decisions create or destroy your company's strategy. AB - Senior executives have long been frustrated by the disconnection between the plans and strategies they devise and the actual behavior of the managers throughout the company. This article approaches the problem from the ground up, recognizing that every time a manager allocates resources, that decision moves the company either into or out of alignment with its announced strategy. A well known story--Intel's exit from the memory business--illustrates this point. When discussing what businesses Intel should be in, Andy Grove asked Gordon Moore what they would do if Intel were a company that they had just acquired. When Moore answered, "Get out of memory," they decided to do just that. It turned out, though, that Intel's revenues from memory were by this time only 4% of total sales. Intel's lower-level managers had already exited the business. What Intel hadn't done was to shut down the flow of research funding into memory (which was still eating up one-third of all research expenditures); nor had the company announced its exit to the outside world. Because divisional and operating managers-as well as customers and capital markets-have such a powerful impact on the realized strategy of the firm, senior management might consider focusing less on the company's formal strategy and more on the processes by which the company allocates resources. Top managers must know the track record of the people who are making resource allocation proposals; recognize the strategic issues at stake; reach down to operational managers to work across division lines; frame resource questions to reflect the corporate perspective, especially when large sums of money are involved and conditions are highly uncertain; and create a new context that allows top executives to circumvent the regular resource allocation process when necessary. PMID- 17345682 TI - Cocreating business's new social compact. AB - Moving beyond decades of mutual distrust and animosity, corporations and nongovernmental organizations (NGOs) are learning to cooperate with each other. Realizing that their interests are converging, the two sides are working together to create innovative business models that are helping to grow new markets and accelerate the eradication of poverty. The path to convergence has proceeded in three stages. In the initial be-responsible stage, companies and NGOs, realizing that they had to coexist, started to look for ways to influence each other through joint social responsibility projects. This experience paved the way for the get-into-business stage, in which NGOs and companies sought to serve the poor by setting up successful businesses. In the process, NGOs learned business discipline from the private sector, while corporations gained an appreciation for the local knowledge, low-cost business models, and community-based marketing techniques that the NGOs have mastered. Increased success on both sides has laid the foundation for the cocreate-business stage, in which companies and NGOs become key parts of each other's capacity to deliver value. When BP sought to market a duel-fuel portable stove in India, it set up one such cocreation system with three Indian NGOs. The system allowed BP to bring the innovative stove to a geographically dispersed market through myriad local distributors without incurring distribution costs so high that the product would become unaffordable. The company sold its stoves profitably, the NGOs gained access to a lucrative revenue stream that could fund other projects, and consumers got more than the ability to sit down to a hot meal-they got the opportunity to earn incomes as the local distributors and thus to gain economic and social influence. PMID- 17345683 TI - In praise of the incomplete leader. AB - Today's top executives are expected to do everything right, from coming up with solutions to unfathomably complex problems to having the charisma and prescience to rally stakeholders around a perfect vision of the future. But no one leader can be all things to all people. It's time to end the myth of the complete leader, say the authors. Those at the top must come to understand their weaknesses as well as their strengths. Only by embracing the ways in which they are incomplete can leaders fill in the gaps in their knowledge with others' skills. The incomplete leader has the confidence and humility to recognize unique talents and perspectives throughout the organization--and to let those qualities shine. The authors' work studying leadership over the past six years has led them to develop a framework of distributed leadership. Within that model, leadership consists of four capabilities: sensemaking, relating, "visioning," and inventing. Sensemaking involves understanding and mapping the context in which a company and its people operate. A leader skilled in this area can quickly identify the complexities of a given situation and explain them to others. The second capability, relating, means being able to build trusting relationships with others through inquiring (listening with intention), advocating (explaining one's own point of view), and connecting (establishing a network of allies who can help a leader accomplish his or her goals). Visioning, the third capability, means coming up with a compelling image of the future. It is a collaborative process that articulates what the members of an organization want to create. Finally, inventing involves developing new ways to bring that vision to life. Rarely will a single person be skilled in all four areas. That's why it's critical that leaders find others who can offset their limitations and complement their strengths. Those who don't will not only bear the burden of leadership alone but will find themselves at the helm of an unbalanced ship. PMID- 17345684 TI - Reputation and its risks. AB - Regulators, industry groups, consultants, and individual companies have developed elaborate guidelines over the years for assessing and managing risks in a wide range of areas, from commodity prices to natural disasters. Yet they have all but ignored reputational risk, mostly because they aren't sure how to define or measure it. That's a big problem, say the authors. Because so much market value comes from hard-to-assess intangible assets like brand equity and intellectual capital, organizations are especially vulnerable to anything that damages their reputations. Moreover, companies with strong positive reputations attract better talent and are perceived as providing more value in their products and services, which often allows them to charge a premium. Their customers are more loyal and buy broader ranges of products and services. Since the market believes that such companies will deliver sustained earnings and future growth, they have higher price-earnings multiples and market values and lower costs of capital. Most companies, however, do an inadequate job of managing their reputations in general and the risks to their reputations in particular. They tend to focus their energies on handling the threats to their reputations that have already surfaced. That is not risk management; it is crisis management--a reactive approach aimed at limiting the damage. The authors provide a framework for actively managing reputational risk. They introduce three factors (the reputation-reality gap, changing beliefs and expectations, and weak internal coordination) that affect the level of such risks and then explore several ways to sufficiently quantify and control those factors. The process outlined in this article will help managers do a better job of assessing existing and potential threats to their companies' reputations and deciding whether to accept a particular risk or take actions to avoid or mitigate it. PMID- 17345685 TI - Understanding customer experience. AB - Anyone who has signed up for cell phone service, attempted to claim a rebate, or navigated a call center has probably suffered from a company's apparent indifference to what should be its first concern: the customer experiences that culminate in either satisfaction or disappointment and defection. Customer experience is the subjective response customers have to direct or indirect contact with a company. It encompasses every aspect of an offering: customer care, advertising, packaging, features, ease of use, reliability. Customer experience is shaped by customers' expectations, which largely reflect previous experiences. Few CEOs would argue against the significance of customer experience or against measuring and analyzing it. But many don't appreciate how those activities differ from CRM or just how illuminating the data can be. For instance, the majority of the companies in a recent survey believed they have been providing "superior" experiences to customers, but most customers disagreed. The authors describe a customer experience management (CEM) process that involves three kinds of monitoring: past patterns (evaluating completed transactions), present patterns (tracking current relationships), and potential patterns (conducting inquiries in the hope of unveiling future opportunities). Data are collected at or about touch points through such methods as surveys, interviews, focus groups, and online forums. Companies need to involve every function in the effort, not just a single customer-facing group. The authors go on to illustrate how a cross-functional CEM system is created. With such a system, companies can discover which customers are prospects for growth and which require immediate intervention. PMID- 17345686 TI - Discovering your authentic leadership. AB - The ongoing problems in business leadership over the past five years have underscored the need for a new kind of leader in the twenty-first century: the authentic leader. Author Bill George, a Harvard Business School professor and the former chairman and CEO of Medtronic, and his colleagues, conducted the largest leadership development study ever undertaken. They interviewed 125 business leaders from different racial, religious, national, and socioeconomic backgrounds to understand how leaders become and remain authentic. Their interviews showed that you do not have to be born with any particular characteristics or traits to lead. You also do not have to be at the top of your organization. Anyone can learn to be an authentic leader. The journey begins with leaders understanding their life stories. Authentic leaders frame their stories in ways that allow them to see themselves not as passive observers but as individuals who learn from their experiences. These leaders make time to examine their experiences and to reflect on them, and in doing so they grow as individuals and as leaders. Authentic leaders also work hard at developing self-awareness through persistent and often courageous self-exploration. Denial can be the greatest hurdle that leaders face in becoming self-aware, but authentic leaders ask for, and listen to, honest feedback. They also use formal and informal support networks to help them stay grounded and lead integrated lives. The authors argue that achieving business results over a sustained period of time is the ultimate mark of authentic leadership. It may be possible to drive short-term outcomes without being authentic, but authentic leadership is the only way to create long-term results. PMID- 17345687 TI - Healthy work environment standards: is your unit up to par? AB - Every RN should be able to work in a safe and healthy environment. Certainly, much of the foundation for such an environment rests with an organization's leadership. But it takes the commitment of every RN to make it happen 24/7. If you did a mini-assessment on your current work environment using the questions above and found it wanting, you have choices to make. First, do you stay silent or do you move the issue forward and seek change? Second, if you advocate for and try to drive change and it doesn't work, do you stay or do you go? Healthy work environments for nurses will only become the norm if nurses refuse to settle for less. PMID- 17345688 TI - Healthy work environments. PMID- 17345689 TI - Flash pulmonary edema in patients with chronic kidney disease and end stage renal disease. AB - Flash pulmonary edema, also termed acute onset pulmonary edema, is characterized by the sudden onset of respiratory distress related to accumulation of fluid in the lung interstitium over a matter of minutes or hours. Chronic kidney disease is often associated with predisposing cardiac risk factors that make patients susceptible to development of flash pulmonary edema. This article highlights the connection between cardiac pathologies found in chronic kidney disease and development of flash pulmonary edema. Nephrology nurses may be instrumental in reducing the risk of flash pulmonary edema by recognizing symptoms of heart failure and need for treatment of acute elevations in blood pressure. PMID- 17345690 TI - The multidimensional characteristics of symptoms reported by patients on hemodialysis. AB - Contemporary theoretical models conceptualize symptoms as multidimensional interactive phenomena. This research examined the symptoms experienced by patients on hemodialysis within this paradigm. The intensity (severity), timing (frequency and duration), distress (bother), and concurrence (co-occurring symptoms) associated with symptoms were explored. A multidimensional profile constructed for each of the symptoms demonstrated that those rated as the most severe were not necessarily the most frequently occurring, longest lasting, or most distressing to patients. Symptoms also occurred in groups. Patients reported individual symptoms as increasingly troublesome and quality of life progressively lower as they experienced more of the symptoms in a grouping. These findings suggest the need to view patients' symptom experiences more broadly. Symptom assessment should include the full complement of symptoms patients experience and move beyond the current practice of assessment of severity alone to include all symptom dimensions. PMID- 17345691 TI - Feasibility of using a personal digital assistant to self-monitor diet and fluid intake: a pilot study. AB - The feasibility of using an electronic device to self-monitor diet and fluid intake was assessed using the treatment implementation model. The three patients on hemodialysis who participated in this pilot study were asked to self-monitor diet and fluid intake for 12 weeks with a personal digital assistant. The intervention was delivered as intended; however, participants reported problems with usability, and compliance to self-monitoring was lower than desirable. Further adjustments to the intervention will be made before testing efficacy. PMID- 17345692 TI - Chronic kidney disease and cardiovascular disease: pathophysiologic links. AB - This is the second in a series of three articles about the risk factors and complications related to chronic kidney disease and their impact on cardiovascular disease. This article focuses on identifying pathophysiologic mechanisms by which two traditional risk factors of cardiovascular disease (hypertension and dyslipidemia), and two nontraditional risk factors associated with chronic kidney disease (anemia and abnormalities in bone and mineral metabolism) contribute to the markedly increased cardiovascular morbidity and mortality seen in individuals with chronic kidney disease. PMID- 17345693 TI - Development of a donor driven assessment protocol in Western Australia based on experiences of living renal donors. AB - A new protocol for the selection and work-up of living renal donors has been developed in response to recent findings from a grounded theory study that explored the experiences of 18 donors in Western Australia. This protocol is designed to enhance the feelings of personal control by the donor over participation in the process and the potential outcome. It includes the coordination of the work-up process by a Clinical Nurse Consultant. PMID- 17345694 TI - Comorbid diseases in patients on dialysis: the impact on anemia. AB - Patients on dialysis frequently present with a multitude of comorbid diseases. Many of these conditions can either directly aggravate preexisting anemia, or lead to acute or chronic inflammatory or infectious conditions that can lower hemoglobin levels. Awareness of these conditions and their compounding effect on anemia can help nurses when interpreting the results of longitudinal trends in hemoglobin and enable them to intervene proactively to minimize the effect of these conditions on hematological parameters. PMID- 17345695 TI - Patients helping patients: the Renal Support Network. PMID- 17345696 TI - The enigma of nephrogenic systemic fibrosis. AB - Nephrogenic systemic fibrosis is a severely physically disabling phenomenon experienced by a specific subset of patients with renal disease. Several of the 200 reported cases worldwide are currently treated within the author's facility. My colleagues and I have witnessed first-hand the life altering effects of NSF on our patients' physical, psychological, and social health, not to mention the unseen effects on family dynamics and changes in the interpretation and function of individual roles. Outside of the ESRD community, NSF is a largely unknown entity, likely due to the infrequency of incidence and relatively cohorted population. Despite the infrequency, we in the nephrology specialty must spread awareness of this condition and share our common knowledge and experiences to help those suffering from NSF to maintain their quality of life. In collaboration with the Centers for Disease Control (CDC), the Yale University International Center for NSF Research has established a website (www.icnfdr.org) for reporting of new cases of NSF/NFD. Until a causative agent is irrefutably identified, it is of the utmost importance that new cases be reported immediately. We expend a great deal of effort and gain valuable experience in helping our patients live their lives as richly as possible. If we as professional nurses share our knowledge and experience in managing the life-altering effects of NSF, our patients as a collective whole will benefit. It is, therefore, our responsibility to collaborate within and outside of the profession to reduce the number of new cases of NSF and help existing patients live their lives with the highest quality standard possible. PMID- 17345697 TI - Disaster readiness: lessons from Katrina. PMID- 17345698 TI - Nutrition and the pediatric patient with CKD. PMID- 17345699 TI - [The emerging field of cochlear implantation in China]. PMID- 17345700 TI - [Forum on cochlear implantation]. PMID- 17345701 TI - [Cochlear implantation in patients with ossified cochleas]. AB - OBJECTIVE: The ossified cochlea was no longer an absolute contra-indication to cochlear implantation but it was still a challenge even for the experienced otologist. To report the condition of cochlear implantation and the hearing results of 31 cases of cochlear ossification. METHODS: Retrospective analysis of cochlear implantation of 720 cases of cochlear implantation from May 1995 to July 2005 in Peking Union Medical College Hospital. RESULTS: Thirty-one cochlear ossification patients was found from all the 720 surgeries which included 27 mild cases and 4 severe ones, 14 males, 17 females. And the age of operation was 1. 4 59. 0 years old , mean age was 13. 2 years old. All of them had cochlear implanted through mastoid-facial recess. There was no complications during or post the operations. And the hearing threshold was about 40 dB in the sound field, the results were similar to those without cochlear ossification. CONCLUSIONS: Although it was difficult of cochlear implantation in cochlear ossification patients, but in most cases especially mild ones all the electrodes could be implanted after clearing the ossified tissue, and had few damage to the electrodes. Now it was possible to practice in the partial cochlea ossification. PMID- 17345702 TI - [Cochlear implantation in patients with otitis media-related diseases]. AB - OBJECTIVE: To evaluate the indications, surgical techniques and complications of cochlear implantation in patients with otitis media-related diseases. METHODS: Retrospective study of the data collected from patients receiving cochlear implantation. Totally 866 cases of cochlear implantation were performed in Peking Union Medical College Hospital from May 1995 to February 2006. Among which, 41 patients with otitis media-related diseases were grouped into 5 types: chronic secretory otitis media (13 cases), silent (subclinical) otitis media (18 cases), dry eardrum perforation (1 case), bilateral cholesteatoma of middle ear (2 cases) and middle ear granuloma (7 cases). Seven cases were accompanied with deformities of middle ear and (or) inner ear. Pedicled aponeurosis of occipitofrontalis muscle was transplanted to cover and protect the inserted electrodes and facial nerve in a patient with bilateral cholesteatoma after radical mastoidectomy. RESULTS: All the 41 patients with otitis media-related diseases were successfully implanted in one stage or staged operations and followed up uneventfully for 5 months to 6 years and 11 months. All implant devices had worked normally and all patients had performed well. CONCLUSIONS: Patients with chronic secretory otitis media, silent (subclinical) otitis media, middle ear granuloma or dry ear-drum perforation could be operated in one stage or staged procedures safely and effectively. Patients with bilateral cholesteatoma could be implanted after radical removal of related lesions. Pedicled aponeurosis of occipitofrontalis muscle could be transplanted in cases of mastoid bowl to cover and protect the inserted electrodes and the exposed facial nerve and with easy access to observe the mastoid cavity. Active suppurative otitis media was contraindicated for cochlear implantation. Long-term following-up was essential for better evaluation of the outcomes of cochlear implantation in patients with otitis media-related diseases. PMID- 17345703 TI - [Summary of forum on cochlear implantation]. PMID- 17345704 TI - [Quality of life for adolescents and children with chronic sinusitis and its influencing factors]. AB - OBJECTIVE: To investigate the status of the quality of life for adolescents and children with chronic sinusitis and its influencing factors. METHODS: Eighty-six patients were measured with the General Information Questionnaire and Chronic Sinusitis Quality of Life Scale. Six months after operation, the Chronic Sinusitis Quality of Life Scale was retested. T-test and stepwise regression were used to study the improvement and influencing factors of quality of life. RESULTS: The preoperative and postoperative quality of life scores showed a significant difference ( all P < 0. 01 ). The main factors influencing the quality of life included symptom scores (P = 0. 003) , family economic status(P = 0. 003) , parents' attitude(P = 0. 009) , extents of pathological changes(P = 0. 019) , regional disparity ( P = 0. 010) and parents' educational level (P = 0. 048). CONCLUSION: The children's subjective symptoms should be viewed as an important aspect for surgery selection. The quality of life in adolescent and children was influenced significantly by family economic status, their parents' attitude and the difference of education. PMID- 17345705 TI - [Diagnosis and surgical management of carotid body tumor as well as blood vessel prosthesis' role]. AB - OBJECTIVE: To analyse the diagnostic and therapeutic aspects of carotid body tumor (CBT). METHODS: Seven patients with CBT had been hospitalized between 2003 and 2006. The clinical data was analyzed retrospectively. The preoperative evaluation included angiography in 7 patients. Most of them had an asymptomatic cervical lateral mass. Only one patient had the hoarseness and buckling and was given radiation therapy alone. Six of seven patients with carotid body tumour underwent surgery. Simple tumor excision was accomplished in 4. Carotid artery resection with the tumor was required in 2 patients and in the both, interposition of a 7 mm polytetrafluoroethylene graft was performed . During the resection, temporary carotid shunt was required in the two patients. RESULTS: All tumors by surgery were identified as carotid paragangliomas without evidence of malignancy. There was no mortality and no hemiplegia. After surgery, temporary cranial nerve dysfunction was noted in one case. In the follow-up period of 2 months to 2 years, no recurrent disease occurred. The patient's tumor who accepted radiotherapy was in the stable stage under the half year follow up, and the follow up would be further continued. CONCLUSIONS: With non-invasive investigation and arteriography it was possible to obtain an early and precise diagnosis. The surgical management was the major treatment of these tumors. The pattern of operation should be chosen according to the relation of tumor and carotid. The decision to perform simple tumor excision or additional arterial resection was based on diagnostic preoperative and after the arterial resection the polytetrafluoroethylene graft would be used for carotid reconstruction. PMID- 17345706 TI - [Exploration of the auditory effects of diabetes mellitus using distortion product otoacoustic emissions]. AB - OBJECTIVE: To investigate the effects of diabetes mellitus on amplitude of distortion product otoacoustic emissions ( DPOAE) and whether streptozotocin has ototoxicity or not. METHODS: Twenty-four SD rats were divided into diabetes mellitus group, insulin therapy group and control group. Diabetes was induced by streptozotocin. The blood glucose of insulin group was controlled by insulin. The amplitude of DPOAE was tested before streptozotocin injection and 3 months, 5 months after injection, respectively. RESULTS: The amplitude of DPOAE in diabetes rats was decreased in 3 months and there was statistical significance (P <0. 05) in 1038, 4126 and 5200 Hz, while obviously reduced in 5 months in all frequencies and there was also statistical significance (P <0. 01). The amplitude of DPOAE in all frequencies lacked of any significance between insulin therapy group and control group. CONCLUSIONS: Diabetes mellitus could induce the amplitude of DPOAE decreasing. Streptozotocin had not evident toxicity for inner ear. PMID- 17345707 TI - [MRNA expression of complement C3 and C4 in rat nasal mucosa with allergic rhinitis]. AB - OBJECTIVE: To investigate the level of mRNA expression of complement C3 and C4 in rat nasal mucosa and to reveal the relationship with the pathogenesis of allergic rhinitis (AR) . METHODS: Twenty healthy SD rats were randomly divided into AR group and control group, 10 rats for each group. Ten rats was sensitized and intranasally challenged by ovalbumin and Al (OH)3 (as supplement) as allergic rhinitis models, and the control group was treated by saline. RT-PCR was performed to investigate the level of mRNA expression of complement C3 and C4 in nasal mucosa of both groups. RESULTS: C3 and C4 mRNA were detected in both groups. The relative intensity of gene expression was measured. The relative intensity of C3 mRNA expression was 6183+/-1376 in AR group, 4444+/-989 in control group, C4 mRNA was 4398 +/-948 in AR group, and 2771+/-407 in control group. Expression of C3 and C4 in AR group was higher than that of the controls ( P < 0. 05) . CONCLUSION: The high level of C3 and C4 mRNA expression in nasal mucosa of rats with allergic rhinitis suggests that C3 and C4 are involved in the immunopathology of allergic rhinitis. The result implies that complement system involved in the rat's allergic rhinitis is possibly activated through the classical pathway. PMID- 17345708 TI - [Application of detecting gene rearrangement in diagnosing and typing of primary non-Hodgkin's lymphoma in nasal cavity]. AB - OBJECTIVE: To evaluate the significance of immunoglobulin heavy chain (IgH) gene rearrangement for B-cell lymphoma and T-cell receptor (TCR) gene rearrangement for T-cell lymphoma and NK/T-cell lymphoma in diagnosing and typing of primary non-Hodgkin's lymphoma (NHL) in nasal cavity. METHODS: Semi-nested polymerase chain reaction ( PCR) with two pairs of primers was used to detect monoclonal IgH gene rearrangement in paraffin-embedded tissues from 11 patients with B-cell lymphoma, and one-stepped PCR with two pairs of primers was used to detect T-cell receptor gene rearrangement from 23 patients with NK/T-cell lymphoma and 20 patients with T-cell lymphoma. Ten patients with nasal polyp were detected with all the primers by PCR respectively. RESULTS: Among the 54 patients with an evaluable PCR results, 10 of 11 (90. 9% ) B-cell lymphomas were positive for monoclonal IgH gene rearrangement, 17 of 20 (85. 0% ) T-cell lymphomas and 10 of 23 (43. 5% ) NK/T-cell lymphomas were positive for monoclonal TCR gene rearrangement. Ten patients with nasal polyp were negative for all detection. CONCLUSIONS: Detecting gene rearrangement was an efficient method in auxiliary diagnosing and typing of primary NHL in nasal cavity; Using semi-nested PCR or one-stepped PCR with two pairs of primers can enhance the positive rate of gene rearrangement detection. PMID- 17345709 TI - [Microsurgical anatomy of epiglottic artery and its clinical implications]. AB - OBJECTIVE: To study the microsurgical anatomy of human epiglottic blood vessel to provide exact and reliable data and morphological properties for further studies of laryngeal transplantation, reconstruction and other epiglottis-related diseases. METHODS: Thirty Chinese adult cadavers (27 males and 3 females) were examined for the present study. The cadavers were dissected under magnification along the anatomic planes from skin down to vertebral column. The anterior neck was exposed by a midline incision and extended laterally along the angle of mandible superiorly, and on clavicle inferiorly. After the visualization of laryngeal prominence of thyroid cartilage, strap muscles were resected and superior laryngeal artery and epiglottic blood vessel were exposed under an operating microscope ( original magnification 7 -30). The epiglottic artery was named for the first time. RESULTS: The diameter of superior laryngeal artery was (1. 06+/-0. 16) mm( male: 1. 09 mm+/-0. 12 mm). The diameter of origin epiglottic artery was (0. 79+/-0. 13) mm (male: 0. 81 mm+/-0. 11 mm). The vertical distance between origin epiglottic artery and superior horn of thyroid cartilage was (27. 16+/-3. 85) mm. Epiglottic artery loop was observed in all the cadavers, which could be M-, N-, omega-, or U-shaped and mixed under the thyrohyoid membrane or in the epiglottic vallecula. CONCLUSIONS: These findings could improve the application of epiglottis in laryngeal functional reconstruction after partial laryngectomy, as well as in the prevention of epiglottic artery loop injuries during the operation. PMID- 17345710 TI - [Experimental investigation of CD133 as a putative marker of tumor-initiating cell in laryngeal carcinoma]. AB - OBJECTIVE: To detect the expression of CD133 in human larynx tumor cell line, Hep 2 cell line and observe proliferation and differentiation ability of CD133+ groups in vitro. METHODS: Immunocytochemical staining and flow cytometry were used to detect the expression of putative tumor-initiating cell marker CD133 in Hep-2 cell line, and the selective technique of immunomagnetic beads was applied to purify CD133 positive cells. CD133+ tumor cells were cultured and their ability of proliferation and differentiation were observed in vitro. RESULTS: Only 3. 22% of cells in Hep-2 cell line expressed CD133. In serum-free RPMI1640, On days 3, 5 and 7, their UV absorption were 0. 320,0. 370 and 0. 558 respectively. Compared with CD133 - cells and control Hep-2 cells, CD133 + cells demonstrated increased proliferation capacity. The proportion of CD133+ cells decreased in culture as days passed. In twelve days of culture, the percentage of CD133+ cells decreased from 90. 88% to 4. 53 %. CONCLUSIONS: CD133 was one of makers for tumor-initiating cell of human laryngeal carcinoma, Hep-2 cell line. Its identification would provide a helpful tool to investigate the tumorigenic process of human laryngeal carcinoma and to develop targeted therapies. PMID- 17345711 TI - [Expression of two kinds of tumor correlation protein in laryngeal carcinoma and precancerous lesions]. AB - OBJECTIVE: To study the expression of S phase kinase associated protein 2 (Skp2), phosphatase and tensin homolog deleted on chromosome ten (PTEN) in human laryngeal carcinoma and precancerous lesions, to explore their relations and clinical significance. METHODS: Formalin-fixed and paraffin-embedded tissues from 79 cases of laryngeal carcinoma, 16 cases of atypical hyperplasia of vocal fold,14 cases of adult laryngeal papillomas and 27 cases of vocal cord polyps were evaluated for the expression of Skp2, PTEN by SP immunohistochemistry, the levels of these proteins in tissues with the different types of lesion and their correlation with clinicopathological parameters of laryngeal carcinoma were analyzed. RESULTS: The expression rates of Skp2 in vocal cord polyps, adult laryngeal papillomas, atypical hyperplasia of vocal cord and laryngeal carcinoma were 11. 11% ,14. 29% ,37. 50% ,39. 24% respectively. There was significant difference among them( Hc = 11. 57, P <0. 01). The expression rates of PTEN protein in vocal cord polyps,adult laryngeal papillomas, atypical hyperplasia of vocal cord and laryngeal carcinoma were 100% ,92. 86% ,75. 00%, 56. 96% respectively . There was significant difference among them (Hc = 62. 86, P<0. 05). There was a negative correlation between the expression of Skp2 and PTEN,and their correlation coefficient was r = -0. 4512(P <0. 01). Patients with Skp2 expression in laryngeal carcinoma revealed poorer five yeas survival rate than patients with negative expression of Skp2 (x2 = 21. 46, P = 0. 000). CONCLUSIONS: The expression of Skp2 and PTEN took important roles in the tumorigenesis, aggressiveness, metastases of laryngeal carcinoma. The high expression of Skp2 was negative correlation with the lower PTEN in laryngeal carcinoma, which suggested that PTEN may regulate the expression of Skp2. PMID- 17345712 TI - [The application of GlideScope videolaryngoscope in head neck tumor operations with difficult tracheal intubation]. PMID- 17345713 TI - [Observation on three kinds of virus infection of the patients suffering from nasopharyngeal carcinoma and heroin addicts]. PMID- 17345714 TI - [Analysis of the causes of postoperative hemorrhage of tracheotomy in patients with liver transplantation]. PMID- 17345715 TI - [Cochlear implantation for Meniere's disease with profond sensorineural hearing loss]. PMID- 17345716 TI - [Pre-operative electrophysiological evaluation for pediatric cochlear implant recipients with auditory neuropathy or auditory dys-synchrony]. PMID- 17345717 TI - [Endoscopic frontal sinus surgery]. PMID- 17345718 TI - The epidemiology of non-fatal injuries among 11-, 13- and 15-year old youth in 11 countries: findings from the 1998 WHO-HBSC cross national survey. AB - The primary objective was to present a cross-country comparison of injury rates, contexts and consequences. The research design was the analysis of data from the 1998 cross-national Health Behaviour in School-aged Children survey and 52955 schoolchildren from 11 countries, aged 11, 13 and 15 years, completed a self administrated questionnaire. A total of 41.3% of all children were injured and needed medical treatment in the past 12 months. Injury rates among boys were higher than among girls, 13.3% reported activity loss due to injury and 6.9% reported severe injury consequences. Most injuries occurred at home and at a sport facility, mainly during sport activity. Fighting accounted for 4.1% of injuries. This paper presents the first cross-national comparison of injury rates and patterns by external cause and context. Findings present cross-country similarities in injury distribution by setting and activity. These findings emphasize the importance of the development of global prevention programmes designed to address injuries among youth. PMID- 17345719 TI - Drownings in Scotland: the real story. AB - The Scottish Accident Prevention Council is responsible for promoting water safety in Scotland. It has long expressed concern that the number of reported drownings in Scotland underestimates the actual figures. The key aims of this study were to establish a valid database of water-based incidents in Scotland and test the under-reporting proposition. A survey involving interviews and correspondence was undertaken to establish the sources of information on drownings. Once identified, a database was established and data for a 7-year period acquired. The study identified the organizations essential to the establishment of a complete database. It also established protocols for gaining annual information. Data analysis confirmed a significant under-reporting of accident data and signalled a number of areas of concern with regard to those most at risk. The study produced, for the first time, a mechanism for recording complete details of drownings in Scotland. PMID- 17345720 TI - Pattern of traffic injuries in Shanghai: implications for control. AB - In China, traffic-related injuries are often treated as transportation issues, called 'accidents'. The objectives of the research are to analyse traffic injury patterns, estimate costs of traffic injuries and provide evidence to develop effective prevention strategies. There were over 1 500 deaths due to traffic related injuries annually in Shanghai from 1987 to 2003, and it is rising year by year with the rate of growth in motorization. The rates of annual increase are 3.59% in fatalities (from 7.78 to 14.18 per 100000 population) and 10.46% in non fatalities (from 53.93 to 264.98 per 100000 population) respectively during the period. The analysis of the geographic information system showed that the geographic distribution of traffic injuries in the countryside regions of Shanghai had the highest rates. Labour force groups represented the majority of fatalities (70.97%) and serious traffic injuries (90.51%). The mortality rates were 18.40 per 100000 population and 10.02 per 100000 population in 45-65 year age group and 15-44 year age group respectively; the morbidity rates of serious traffic injuries were 121.60 per 100000 population and 70.46 per 100000 population in the same groups respectively. And females generally showed a lower incidence than males. In general, fatalities and injuries were higher for drivers, bicyclists and pedestrians. Among road traffic injury-related fatalities, 66.8% were attributed to head injuries. Of those with fatal head injuries, bicyclists accounted for 29.8% of the total; pedestrians accounted for 28.3%; motorcyclists accounted for 25.5%. Total traffic injury cost was estimated at least US $645989580 in Shanghai in 2003. Good injury intervention programmes need to be done as soon as possible to effectively reduce traffic injury burden in Shanghai, China. PMID- 17345721 TI - The neighbourhood socio-demographic context of teenage girls' deliberate self harm. AB - This study investigates whether living area characteristics relate to the commission of self-inflicted injuries and to psychiatric consultation among teenage girls. An ecological study was conducted at the parish level. Seven descriptors of the population's sociodemographic composition were selected and psychiatric health care seeking and hospitalization for deliberate self-harm (DSH) among girls aged 12-19 years were considered (years 1999-2003). For each parish characteristic, three levels of concentration were determined and health outcomes were compared between levels using rate ratios (RR). Acute psychiatric consultation was strongly associated with all parish characteristics, particularly with the concentration of female-headed households. For hospitalization for DSH, RR were significantly higher in parishes with higher concentrations of female-headed poor families, social welfare recipients and low income people. Teenage girls' acute psychiatric consultations more than their rate of DSH injuries are affected by parish compositional characteristics. The contextual, family-related and individual mechanisms lying behind this deserve further investigation. This may have implications for prevention strategies and for the allocation of care. PMID- 17345722 TI - Adolescent injuries in Canada: findings from the Canadian community health survey, 2000-2001. AB - This article presents a description of injuries among 24312 Canadian adolescents, aged 12-24 years, based on the Canadian Community Health Survey, 2000-2001. A total of 3214 (25.6%) males and 2227 (16.5%) females reported having at least one serious injury in the past year. The leading causes of injury in adolescents were: falls; overexertion or strenuous movement; accidentally bumped, pushed or bitten; and accidentally struck or crushed by objects. The parts of the body most often affected were the ankles/feet, wrists/ hands and knees/lower legs. The most frequent locations of injuries were: sports or athletic areas; home; school, college or university areas; and the street, highway or pavement. Injuries were more often reported to have occurred during the summer months. Low socio-economic status was inversely associated with the occurrence of injury in the past year whereas risk-taking behaviour in the form of cigarette smoking and drinking alcohol was positively associated with injury occurrence. PMID- 17345723 TI - Trauma epidemiology and outcome in a developing country: perspectives from a university teaching hospital in Beirut. AB - This study aims at evaluating trauma care at the American University of Beirut Medical Centre (AUB-MC) and comparing it to the norms established by the Major Trauma Outcome Study (MTOS). From January 2001 until January 2003, data necessary to calculate probability of survival using the Trauma Injury Severity Score methodology were collected. M, W, Z, Ws and Zs statistics were calculated to compare outcome at AUB-MC to the MTOS dataset. A total of 873 patients were included in the study. W statistics was calculated at 0.35 with Z score for the overall sample of 0.081 indicating that there was no statistically significant difference in survival between this group and the MTOS group. In a developing country a hospital achieves trauma outcomes similar to the MTOS dataset. Further studies looking at trauma care in Lebanon as a whole are needed. PMID- 17345724 TI - Road traffic accident trends in Nigeria. PMID- 17345725 TI - Toddler drowning prevention: teaching parents about water safety in conjunction with their child's in-water lessons. AB - The primary objective of the study was to develop a parent education programme that addressed parental misconceptions of toddler water safety previously identified by the authors. Parents (n = 106) of 2-4-year-old toddlers enrolled in swim school lessons completed a self-directed questionnaire before and after a 10 week poolside water safety programme. Differences in pre- and post-programme knowledge and beliefs were measured by frequency and chi-square tested to identify significant changes in parental comprehension of toddler water safety after the programme. Statistically significant improvements in parental understanding were evident after the programme. More parents were aware of the family or friend's swimming pool as the primary site of toddler drowning (59% vs. 78%). More parents agreed that their toddler required more, not less, adult supervision after swimming lessons (85% vs. 97%) and more disagreed that swimming lessons were the best way to prevent toddler drowning (65% vs. 74%). Parental understanding of child cardiopulmonary resuscitation (CPR), however, did not improve after the programme. This study suggests that toddler lessons in swim schools provide a valuable opportunity to address parental misconceptions about toddler water safety. Further research is required to determine how parents whose toddlers do not attend swimming lessons might similarly benefit from such a programme. PMID- 17345726 TI - Pattern of paediatric injuries in Jos, Nigeria. PMID- 17345727 TI - Correct and incorrect use of child restraints: results from an urban survey in New Zealand. AB - This study describes the incorrect use of child restraints among car drivers with young children and examines factors that may influence their misuse. A cross sectional survey was undertaken in supermarket car parks with car drivers travelling with children under the age of 8 years. The main measure was errors in child restraint use. Short interviews were conducted with 1113 drivers with a close inspection of the child restraints used in the vehicles. Only 4% of children were unrestrained but 64% of drivers made at least one error in restraint use. Most respondents thought using a restraint was easy, but 65% of these drivers made at least one error. Child restraints are used, but many are incorrectly fitted and/or have the child incorrectly placed in them. Correct use is a moderately complex task. Restraint systems need to be designed to minimize the opportunity for error and maximize safety. PMID- 17345728 TI - Evaluation of school safety in Riyadh. PMID- 17345729 TI - Record linkage: a tool for injury prevention research. PMID- 17345730 TI - Approaches to crystallization from ionic liquids: complex solvents-complex results, or, a strategy for controlled formation of new supramolecular architectures? AB - There are now more than 1200 papers a year describing research results using the 'neoteric' solvents, known as ionic liquids (ILs). If ILs are such highly studied solvents, why has there been so comparatively little research in their use in crystallization? Here we explore this question and discuss possible strategies for utilization of the mundane and the unique aspects of ILs for novel crystallization strategies including crystallization of high and low melting solids using thermal shifts; "solvothermal" techniques; slow diffusion; electrocrystallization; and use of a co-solvent. The results presented here and those appearing in the literature indicate both the complex nature of these solvents and their promise in delivering unique solvation, metal ion coordination numbers, coordination polymer motifs, and metal-anion interactions, to name but a few. These complex, but fascinating, results and the promise of much more intimate control over crystallization processes will drive a growing interest in using ILs as crystallization solvents. PMID- 17345731 TI - Structural diversity and chemical trends in hybrid inorganic-organic framework materials. AB - Hybrid framework compounds, including both metal-organic coordination polymers and systems that contain extended inorganic connectivity (extended inorganic hybrids), have recently developed into an important new class of solid-state materials. We examine the diversity of this complex class of materials, propose a simple but systematic classification, and explore the chemical and geometrical factors that influence their formation. We also discuss the growing evidence that many hybrid frameworks tend to form under thermodynamic rather than kinetic control when the synthesis is carried out under hydrothermal conditions. Finally, we explore the potential applications of hybrid frameworks in areas such as gas separations and storage, heterogeneous catalysis, and photoluminescence. PMID- 17345732 TI - Fine-tuning of optical properties with salts of discrete or polymeric, heterobimetallic telluride anions [M4micro4-Te)(SnTe4)4](10-) (M = Mn, Zn, Cd, Hg) and 3{[Hg4(micro4-Te)(SnTe4)3](6-)}. AB - Compounds with first discrete M/Sn/Te anions--exhibiting a series of optical absorption energies in the semiconductor range-are obtained by reactions of K+ or Rb+ salts of [SnTe4](4-) with MCl2 (M = Mn, Zn, Cd, Hg) in H2O or H2O-MeOH; larger Cs+ cations provoke the formation of a polymeric derivative of the ternary anionic structure. PMID- 17345733 TI - Binary inorganic salt mixtures as high conductivity liquid electrolytes for >100 degrees C fuel cells. AB - We report the successful application of low-melting inorganic salts with protonated cations (e.g. ammonium) as electrolytes in fuel cells operating in the temperature range 100-200 degrees C, where even with unoptimized electrodes, cell performance is comparable to that of the phosphoric acid fuel cell operating with optimized electrodes in the same temperature range, while open circuit voltages, and efficiencies at low current densities, can be much better--and there is no need for humidification or pressure to sustain performance. PMID- 17345734 TI - Investigation of laser induced photocurrent generation experiments. AB - Current signals produced by the laser-illumination of bare and non-chromophore containing peptide modified gold electrodes were investigated, and we suggest that these current signals which are due to the interfacial potential drop induced by laser heating, may have been mistakenly assigned to molecular-based photocurrents in several recent publications. PMID- 17345735 TI - A highly water-soluble C60-NVP copolymer: a potential material for photodynamic therapy. AB - Water-soluble C60 polymers, which have the highest solubility of fullerene reported to date (7.8 mM of C60 in water), were prepared via copolymerization, and showed significant visible light-induced O2*- generation and DNA cleavage, indicating the potential of these water-soluble fullerene derivatives as agents for photodynamic therapy. PMID- 17345736 TI - Metal-organic frameworks exhibiting strong anion-pi interactions. AB - Coordination polymers offer a significant potential for applications in adsorption, guest and anion recognition and sensing. Their structure commonly provides binding sites for such specific interactions as pi-pi stacking and XH...pi hydrogen bonding. The latter reflects the ability of the pi-cloud to interact with positively polarized atoms. An electrostatic interaction between anionic species and electron deficient heterocycles, which parallels the above binding scheme, is also possible and very recently the existence of anion-pi interactions was proved in the solid state and in solution. This effect may be significant also for biomolecule/solution interfaces, as it occurs in protein structures. In fact, such interactions could be especially relevant for host guest chemistry of coordination polymers, particularly for functionalization of hydrophobic crystal cavities and for the design of geometrically rigid anion receptors. However, typical electron deficient heterocycles such as 1,3,5 triazines and 1,2,4,5-tetrazines are very weak donors and they are hardly suitable for bridging metal ions and the generation of coordination frameworks. As a system that combines efficient donor properties towards transition metal ions and a pronounced ability for anion-pi interactions we have developed unsubstituted pyridazino[4,5-d]pyridazine, which was readily accessible by a novel one-pot synthesis involving inverse electron demand Diels-Alder cycloaddition (Scheme 1). Unusual anion binding properties of the ligand may be clearly related to its electron-deficiency (LUMO energy -1.591 vs. -0.288 eV for the parent pyridazine), influenced also by N-coordination to such Lewis acids as metal ions. PMID- 17345737 TI - InAs(x)Sb(1-x) alloy nanocrystals for use in the near infrared. AB - InAs(x)Sb(1-x) alloy nanocrystals for the near-infrared, which have quite a monodisperse crystalline structure of 2.5-3.0 nm and are of a zinc blend structure, are developed. PMID- 17345738 TI - Microwave enhanced palladium catalysed coupling reactions: a diversity-oriented synthesis approach to functionalised flavones. AB - Microwave enhanced diversity-oriented synthesis (MEDOS) using palladium catalysed protocols is introduced as a powerful new strategy for the synthesis of systematically modified small molecules and is highlighted by application to functionalised flavones. PMID- 17345739 TI - A new consecutive three-component oxazole synthesis by an amidation-coupling cycloisomerization (ACCI) sequence. AB - A novel consecutive three-component synthesis of 1-(hetero)-aryl-2-(2 (hetero)aryl-oxazol-5-yl) ethanones starting from propargyl amine and acid chlorides, both for amidation and cross-coupling, is based upon an amidation coupling-cycloisomerization (ACCI) sequence. PMID- 17345740 TI - Temperature, ionic strength and pH induced electrochemical switching of smart polymer interfaces. AB - A reversible electrochemical switching has been displayed at smart polymer brush interfaces, which was responsive to temperature, ionic strength and pH stimuli, independently or simultaneously. PMID- 17345741 TI - Cytochrome P-450 model compound catalyzed selective hydroxylation of C-H bonds: dramatic solvent effect. AB - Selective hydroxylation of cyclohexane and cyclohexene by t-BuOOH in presence of F2oTPPFe(III)Cl as the catalyst has been achieved at room temparature in high yields. PMID- 17345742 TI - The use of calcium carbide in one-pot synthesis of symmetric diaryl ethynes. AB - An efficient Pd-catalyzed copper and amine free coupling reaction of acetylene and aryl bromides was achieved with calcium carbide as an acetylene source, using inorganic base and easily prepared, air-stable aminophosphine ligand in common organic solvents, providing symmetric diaryl ethynes in one-pot with yields ranged from moderate to excellent. PMID- 17345743 TI - Water-soluble diruthenium complexes bearing acetate and carbonate bridges: highly efficient catalysts for aerobic oxidation of alcohols in water. AB - The aerobic oxidation of alcohols in water can be performed efficiently in the presence of a catalytic amount of the water-soluble diruthenium complex Ru2(micro OAc)3(micro-CO3) under an atmospheric pressure (1 atm) of O2. PMID- 17345744 TI - Watson-Crick pairing of nucleobases functionalized with open-shell molecular entities in crystalline solids. AB - A Watson-Crick type molecular complex of adenine and thymine bases substituted with the stable radical of nitronylnitroxide has been synthesized, which forms a double-chain spin system in the crystal. PMID- 17345745 TI - A flow reactor process for the synthesis of peptides utilizing immobilized reagents, scavengers and catch and release protocols. AB - A general flow process for the multi-step assembly of peptides has been developed and this procedure has been used to successfully construct a series of Boc, Cbz and Fmoc N-protected dipeptides in excellent yields and purities, including an extension of the method to enable the preparation of a tripeptide derivative. PMID- 17345746 TI - A new asymmetric organocatalytic nitrocyclopropanation reaction. AB - Using 5-(pyrrolidin-2-yl)-1H-tetrazole as an organic catalyst, the nitrocyclopropanation of 2-cyclohexen-1-one has been achieved, proceeding in high yield and with good enantioselective control. PMID- 17345747 TI - Stereoselective formation of a single-stranded helicate: structure of a bis(palladium-allyl)quaterpyridine complex and its use in catalytic enantioselective allylic substitution. AB - Chiral C2-symmetric quaterpyridine L reacts with [Pd(eta3-C3H5)Cl]2 to form a chiral single-stranded helical binuclear palladium complex of formula [Pd2(eta3 C3H5)2(L)]2+; the complex can efficiently catalyze allylic substitution of 1,3 diphenylprop-2-enyl acetate with dimethyl malonate with enantioselectivity up to 85%. PMID- 17345748 TI - Facile preparation of fluorovinylene aryl ether telechelic polymers with dual functionality for thermal chain extension and tandem crosslinking. AB - New fluorovinylene aromatic ether polymers, possessing dual reactivity, have been successfully prepared via the step-growth polymerization of commercial bis(trifluorovinyl) aromatic ethers and bisphenols. PMID- 17345749 TI - Self-assembly of cyclic homo- and hetero-beta-peptides with cis- furanoid sugar amino acid and beta-hGly as building blocks. AB - The design, synthesis and characterization of a new class of peptide nanotubes, self-assembled from cyclic homo- and hetero-beta-peptides based on cis-furanoid sugar amino acid and beta-hGly residues are described; these results represent the expansion of the conformational pool of cis beta-sugar amino acids in the design of peptide nanotubes. PMID- 17345750 TI - Phosphazene base-promoted functionalization of aryltrimethylsilanes. AB - The activation of Ar-Si bonds in aryltrimethylsilane was investigated using a catalytic amount of t-Bu-P4 base and selective functionalizations of aryltrimethylsilanes in the absence of strong electron withdrawing groups on the aromatic rings were accomplished. PMID- 17345751 TI - Reductive disproportionation of carbon dioxide by a sm(II) complex: unprecedented f-block element reactivity giving a carbonate complex. AB - A macrocyclic organosamarium(II) complex has been shown to provide the first example of the reductive disproportionation of carbon dioxide, giving a bimetallic carbonate complex and carbon monoxide in a facile reaction under ambient conditions. PMID- 17345752 TI - Direct reactions of tellurium tetrahalides with chelating nitrogen ligands. Trapping of TeL2 by a 1,2-bis(arylimino)acenaphthene (aryl-BIAN) ligand and C-H activation of an alpha,alpha'-diiminopyridine (DIMPY) ligand. AB - The reaction of TeI4 with the 2,6-diisopropylphenyl-substituted 1,2 bis(arylimino)acenaphthene ligand dpp-BIAN results in two-electron reduction of tellurium and formation of the complex (dpp-BIAN)TeI2, while treatment of TeCl4 with the alpha,alpha'-diiminopyridine ligand dpp-DIMPY causes C-H activation of an imino methyl group. PMID- 17345753 TI - Nitrogen-containing carbon nanotubes as solid base catalysts. AB - Nitrogen-containing carbon nanotubes (NCNT) are effective re-usable solid base catalysts, their activity for a Knoevenagel condensation being related to the amount of pyridinic nitrogen incorporated in the NCNT structure, which could be tuned by the synthesis parameters of the catalyst. PMID- 17345754 TI - Care needs and level of care difficulty related to hip fractures in geriatric populations during the post-discharge transition period. AB - The objective of this study was to understand the following: (1) the specific care needs of geriatric hip fracture patients; (2) the level of care difficulty during the transition period following discharge; and (3) the correlation amongst demographics, the physical function status of the elderly, and care needs. Purposive sampling was used, and a total of 71 hip fracture cases and their caregivers were selected. A survey was carried out to collect data just before discharge and one week following discharge. Statistical methods included descriptive statistics, correlation analysis, one-way ANOVA, and a paired t-test. Results were as follows: Most geriatric patients depended upon care from family members before discharge, with an average physical function status score of 6.99 (0 to 18) that improved significantly after one week to 10.27; paired t = -7.956 (p < .000). The mean age of primary caregivers was 51.72 years old (SD = 14.05). Most caregivers (47, or 66.2%) were female. The relationship between elderly participants and their primary caregiver was predominantly that of husband and wife (22 people; 31.0%). Participant care needs identified included return visit assistance, awareness of safety at all times, assistance with cleaning and maintaining living quarters, and so on. Caring tasks that were identified as more difficult for the primary caregivers includes providing stair climbing assistance, emotional problems management assistance, walking training assistance, rehabilitation assistance, and emergency disease management assistance. The care needs of the elderly in this study and level of execution difficulty for caregivers was found to be negatively related to the physical function status of the elderly. The study results suggest that providing patient related home care knowledge to primary caregivers prior to discharge from the hospital and enhancement of the social support system are both needed. PMID- 17345755 TI - Exploring health behavior determinants for people with chronic illness using the constructs of planned behavior theory. AB - The theory of planned behavior (TPB) has been successfully applied to various health behaviors. Previous research using this theory has not described the health behaviors of Taiwanese people diagnosed with various different chronic illnesses. Because TPB constructs and determinants are abstract, qualitative interviews were conducted with 36 people with various chronic illness diagnoses to identify such determinants and establish measurement indicators for further quantitative study. Content analysis of responses identified the determinants of attitude affecting adoption of health behaviors, both in terms of encouraging and discouraging adoption. The major referents that influenced health behavior adoption included family members, social networks, and health professionals. The determinants of perceived behavioral control included making health behavior easy and hindering health behavior. These findings provide a new glimpse into the application of the theory of planned behavior on the health behavior of the chronically ill population. PMID- 17345756 TI - Cross-mapping ICNP terms with Taiwanese gynecological nursing records. AB - Cross-mapping the terms of International Classification for Nursing Practice (ICNP) with the handwritten nursing records of gynecological patients at one district of private teaching hospital in the south of Taiwan was conducted in July and August, 2004. The purpose of this study was to validate the applicability of ICNP for electronic nursing records in a gynecological setting. A Chinese version of the ICNP beta 2 browser was used to code nursing record sentences. Medical charts were reviewed until data were saturated. A total of sixty-two patient records were analyzed, producing 6,327 sentences, this included 1,918 sentences on nursing phenomena (30.3%) and 4,409 sentences on nursing action (69.7%). The ratio between the two was about 1:2.3. Coded sentences were compared according to the four levels of applicability with the original records, each was identified as a "perfect fit", "conceptual fit", "partial fit", or "unable to fit". Of the 6,327 sentences, 2,041 (32.3%) were designated as "perfect fit", 2,457 (38.8%) as "conceptual fit", 1,663 (26.3%) as "partial fit", and 166 (2.6%) as "unable to fit". The top ten most described nursing phenomena included: acute pain, high temperature, conscious change, potential infection risk, state of mind change, potential risk patient's mobility change endurance level, gastrointestinal function obstacles, changes in urination, anxiety, and diarrhea. The top ten most described nursing actions included: observe surgical wounds, monitor vital signs, changes of mentality, instruction on medication, arranging clinical check ups, wound infection prevention, urinary drainage tube and urine nature observation, checking for vaginal drainage, pre/post-operative healthcare, and discharge planning. Study results indicated that 71.1% of sentences could be cross-mapped. Further validation is suggested to validate ICNP in other gynecological hospitals. PMID- 17345757 TI - The grief reactions of nursing students related to the sudden death of a classmate. AB - More than one-thousand adolescents are killed in accidents in Taiwan every year. Developmental factors shape young people's various reactions and responses to the death of their peers. While counseling research has been conducted in a few studies to address this issue of general bereavement, there remains a need for more knowledge on the grieving process and the needs of undergraduate nurse students who experience the loss of a classmate. The purpose of this study was to explore nursing student fears of death and their grief reactions in such a situation. The phenomenological method was used to uncover the meanings of eleven 19-year-old female nursing students' feelings and narratives about their grieving process in relation to the loss of a classmate, who died in a car accident. All interviews were tape recorded and then transcribed. Descriptions were analyzed using Colaizzi's phenomenological methodology (Colaizzi, 1978). The following core themes emerged from the data: morbid anxiety, helplessness after death, fear of disappearance, and thinking of one's own future. The study also found that, while nursing students could cope with their grief, they rarely shared their feeling with others. Young nursing students require careful step-by-step caring to pass successfully through the grieving process. In view of this gap, this study aspires to serve as a useful reference in understanding the sense of loss felt by grieving young people and providing effective and individualized bereavement counseling to nursing students. PMID- 17345758 TI - Using the Minimum Data Set to determine predictors of terminal restlessness among nursing home residents. AB - The aim of this study was to determine predictive variables of terminal restlessness that were selected from the Minimum Data Set (MDS) among nursing home residents. A descriptive, cross-sectional design was used to retrospectively review decedents' Minimum Data Set records. Four independent variables from the MDS (distressed mood, problem conditions, pain, and medications) were examined as to whether they were predictive variables of terminal restlessness by utilizing path analysis statistical method. Residents from a nursing home located in the northwestern United States who died during 2000 and 2001, had at least one MDS record and no comatose in their MDS cognitive patterns were selected. A total of 84 decedents' records were consequently recruited for use in this study. A path analysis result showed (a) 44.6% of the variance in distressed mood is predicted by two variables: problem conditions (beta = .557) and pain (beta = .193) and (b) 34% of the variance in terminal restlessness is predicted by two variables: pain (beta = .370) and distressed mood (beta = .313). Results indicate that residents who (a) had more problem conditions and more pain are more likely to have distressed moods and (b) experienced more pain and had more distressed moods have a higher incidence of terminal restlessness. These findings provide important and valuable clinical implications. A careful evaluation of pain is necessary, especially as many elders are not able to communicate well during the terminal phase of their lives. How to access residents' moods and provide appropriate and immediate interventions, comfort, and even just being there for them are imperative for nursing home care providers. PMID- 17345759 TI - Effects of tub bathing procedures on preterm infants' behavior. AB - Although medical advances have increased the survival rate of preterm infants, morbidity in terms of neurodevelopmental impairment has not decreased for this population. This results in caregivers having to reconsider how neonatal intensive care unit (NICU) caregiving impacts on preterm infants. The purpose of this study was to examine the effects of different phases of a routine tub bath on preterm infants' distress and state behavior in the NICU. The study used an exploratory repeated measures design that focused on preterm infants' distress and state behavior, and evaluated the effects of three phases of a routine tub bath, which were performed according to standard unit practice in the NICU. Thirteen nurses repeatedly bathed 12 infants on different days, and 64 baths were videotaped for the purpose of assessing the variety of distress behavior. The procedures of one bath could be categorized into three phases designated to Phases I, II, and III. The variables were measured by a preterm infant behavioral coding scheme developed for this research. The inter-rater reliability of the instrument ranged from .82 to .99. Mixed effects analysis of variance was used to analyze the differences among the bath phases in the occurrences of distress and state behavior. The results showed significant statistical difference among most distress behaviors during the three phases (e.g. "startle, jerk, tremor" F ratio = 25.62, p < .001; "finger splay, grasping, fisting" F ratio = 49.99, p < .001; "grimace" F ratio = 36.55, p < .001; "fussing or crying" F ratio = 25.27, p < .001), with the exception of "extension, arching and squirming". In particular, the occurrence of distress and state behavior increased significantly in phase II. Routine tub bathing not only disrupts preterm infants' sleep but also causes an increase in distress behavior. Preterm infants' stress increases with the intrusiveness of nursing procedures. NICU caregivers should consider the effects of routine nursing activities that influence the infants, and modify handling to promote techniques to promote preterm infants' recovery, growth and development. PMID- 17345760 TI - A comparison of MICU survival prediction using the logistic regression model and artificial neural network model. AB - Under the policy of restraint in medical expenditure and with the dual pressures of medical technology development and population aging, the critical care services will exert even greater pressure on the limited medical resources. Therefore, the objective of this study is to compare the abilities of two models, the Logistic Regression Model and the Neural Network Model, to predict the survival of critical care patients, in order to provide a more ethical and objective survival prediction system, as well as to promote more effective management of the resources of the medical intensive care unit (MICU). The two models use the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) and Glasgow Coma Scale (GCS) scores of 1,496 patients stayed who in the MICU of a Taiwan medical center during January 2002-January 2004 to conduct the survival prediction. The study results show that the Neural Network Model has a better predictive ability than the Logistic Regression Model both with regard to the survivors (86.7%, n = 361) and with regard to the entire population of patients studied (74.7%, n = 498). PMID- 17345761 TI - Significant experiences of token therapy from the perspective of psychotic patients. AB - The purpose of this study was to explore the perceived the significant experiences of psychiatric patients related to token therapy. A qualitative in depth interview was applied to collect individual opinions and perceptions. The 13 patients included in this study, all of whom had been diagnosed with mental disorders, received a six-month program of token therapy. Semi-structured interviews of approximately 40 minutes each were held with each participant and transcribed for further analysis in accordance with the principals of content analysis. The three significant domains of experience of participants receiving token therapy included: (1) acknowledgement of token therapy significance, (2) appreciation of each step in terms of personal achievement, and (3) reinforcement from personal changes and family support. Findings support the application of token therapy in psychiatric rehabilitation settings using the strategy of applying appropriate positive or negative logos to communicate reinforcement in an immediate manner that is further enhanced by the public tracking of accumulated patient scores on an evaluation board. In this manner, the therapeutic environment is imbued with a critical empowerment function. The effective application in the future of token therapy in mental health rehabilitation programs is recommended. PMID- 17345762 TI - [Assessment of human sperm function and clinical management of male infertility]. AB - In this article, we provide an update review on the implication of the assessment of human sperm function and the management of male infertility in clinical assisted reproductive technology (ART) known as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). In most ART clinics, the assessment of male fertility is still mainly based on routine semen analysis but it is inaccurate in predicting sperm fertilizing ability. Thus it is often difficult to determine if IVF or ICSI will be an optimal treatment for patients in the initial cycle. Before introduction of ICSI, frequency of low ( <30%) fertilization rate in IVF was very high (20-35% of patients). Evidence suggests that sperm defects are the major contributors to complete failure of fertilization in IVF. Most common sperm defects are oligozoospermia, asthenozoospermia and teratozoospermia though many of the patients are shown to be normal in routine semen analysis. In the literature, many new sperm function tests have been developed, including sperm DNA normalities assessed by Acridine Orange (AO), sperm-zona pellucida (ZP) binding, the ZP-induced acrosome reaction (AR) , sperm-ZP penetration and recently hyaluronan binding assay (HBA). For routine semen analysis, sperm morphology is one of the most useful values for the prediction of sperm function but is also the most difficult test to perform accurately and consistently. Oocytes that failed to fertilize in clinical IVF/ICSI are valuable biological materials for testing sperm function. The human ZP selectively binds sperm with normal morphology and an intact acrosome. The ZP-induced AR is highly correlated with sperm-ZP penetration and disordered ZP-induced AR causes infertility in about 25% men with unexplained infertility with normal semen analysis. Both oligozoospermic (sperm count < 20 x 10(6) /ml) and severe teratozoospermia (strict normal sperm morphology < or =5%) men have a very high ( >70%) frequency of defective sperm-ZP interaction. Thus patients with defects of sperm-ZP interaction should be identified and treated with ICSI since they have high risk of low or zero fertilization rate in IVF. HBA test highly correlates with sperm motility and normal morphology but provides no additional information about sperm fertility. Clinical value of sperm DNA normalities detected by AO for the prediction of ART outcomes is currently still inconclusive and requires further investigation. In conclusion, addition of some of these new sperm tests to routine semen analysis could significantly improve the management of male infertility in clinical ART. PMID- 17345763 TI - [Cell apoptosis and proliferation in the transition and peripheral zones in human prostate]. AB - OBJECTIVE: To determine and compare the difference of cell apoptosis and proliferation in the transition and peripheral zones in the human prostate. METHODS: Seventeen normal prostate glands from organ donors were sampled from normal men according to McNeal/s zonal anatomy, and 20 hyperplastic transition zones obtained from prostatectomy specimens of BPH patients. Cell proliferation and Bcl-2 expression were assessed by immunostaining using PCNA and anti-Bcl-2 antibodies, while apoptotic bodies were specifically stained using TUNEL. Bcl-2 mRNA expression was detected by RT-PCR. RESULTS: In the normal epithelium, the rates of cell proliferation and apoptosis were markedly decreased in the transition zone as compared with the peripheral zone. The proliferation index was significantly increased in the hyperplastic transition zone in BPH, while the apoptosis index significantly decreased in comparison with the normal prostate. Bcl-2 was significantly greater in the normal transition epithelium than in the peripheral zone, and over-expressed in the hyperplastic transition zone. There was a significant negative correlation between the Bcl-2 expression and the apoptosis of the epithelial cells in the hyperplastic transition zone (r(s) = 0.867, P < 0.01). CONCLUSION: The hyperplastic transition zone may result from both an increase of cell proliferation and a failure of cell apoptosis. Increased expression of Bcl-2 may participate in the BPH process by blocking cell apoptosis. PMID- 17345764 TI - [Radioligand binding assay of progesterone receptors on normal fertile human sperm membrane]. AB - OBJECTIVE: To investigate the progesterone-binding site on the normal fertile human sperm membrane after 2 hours of in vitro capacitation. METHODS: Viable spermatozoa were selected by a swim-up method. After 2 hours of in vitro capacitation, multipoint saturation binding experiments were performed. Sperm suspension and increasing concentrations of progesterone-11alpha-glucuronide [125I] iodotyramine (125I-P) were added to 7 total binding tubes respectively, and equal amounts of sperm suspension and 125I-P were added to another 7 corresponding non-specific binding tubes in the presence of 10 micromol/L progesterone. After incubation for 1 hour at 4 degrees C, the radioactivity of both the tubes and the pellets after centrifugation was measured respectively. The equilibrium dissociation constant (Kd) and maximum binding capacity (Bmax) were calculated using the mathematical model of single site multi-point saturation method of Scatchard function and least-squares regression. RESULTS: Kd was (0.61 +/- 0.04) nmol/L and Bmax was (830 +/- 344) sites/cell. The significance test of the regression equation indicated that r = -0.980, P < 0.01. CONCLUSION: There is a high affinity and low capacity binding site for the progesterone (progesterone receptor) on the normal fertile human sperm membrane. PMID- 17345765 TI - [IIEF-5 cannot be used as a tool for differential diagnosis of vasculogenic erectile dysfunction]. AB - OBJECTIVE: To evaluate the 5-item version of the international index of erectile function (IIEF-5) as a method to differentiate the causes of vasculogenic erectile dysfunction (ED). METHODS: In all, 103 ED patients (mean age 46.8 +/- 18.7) were reviewed by IIEF-5. Penile blood flow was also assessed in each patient after an intracavernosal injection (ICI) and audio-visual sex stimulation by duplex Doppler ultrasonography. The 99mTc-(113m)In dual radioisotope test was performed to confirm specific vascular causes in the vasculogenic ED cases. Kruskal-Wallis TEST was employed to compare the scores of IIEF-5 with the results of ICI, duplex Doppler ultrasonography and the 99mTC-(113m)In dual radioisotope test. RESULTS: Of the total number of ED cases, 37 (37/103, 35.9%) were nonvasculogenic, 18 (18/103, 17.5%) arteriogenic, 35 (35/103, 34.0%) venogenic and 13 (13/103, 12.6%) combined vasculogenic. There was no significant difference in the IIEF-5 scores either between the vasculogenic group and the non vasculogenic one (P = 0.253) or among different groups of the vasculogenic ED patients. CONCLUSION: IIEF-5 cannot be used as a tool for differential diagnosis of vasculogenic ED, or to compare its specific vascular causes, nor can the scores of IIEF-5 reflect penile vascular conditions. PMID- 17345766 TI - [Comparison of sperm parameters between male adults at different altitudes]. AB - OBJECTIVE: To investigate the influence of long-term anoxic exposure on the sperm function of male adults at different altitudes. METHODS: A total of 28 male adults that had stayed at the altitude of 5 340 m for 1-3 years were included as a high-altitude group (HAG), 34 at the mean altitude of 3 800 m for 2-5 years as a middle-altitude group (MAG) and 31 permanently at the altitude of 1 300 m as controls. Semen specimens were collected and the real-time semen analysis was performed by using computer-assisted semen analysis (CASA) system. RESULTS: The sperm density, VCL, VSL, VAP and LIN in the HAG were (51.12 +/- 14.61) x 10(6)/ ml, (48.17 +/- 13. 52) microm/s, (32.64 +/- 6.70) microm/s, (41.21 +/- 9.32) microm/s and 52.24 +/- 8.14, respectively, significantly lower than those of the control (P < 0.01 or P < 0.05). Compared with the control group, there was a progressive decrease in sperm concentration, sperm motility rate, VSL, VCL, LIN, VAP and ALH in the MAG. CONCLUSION: The higher the altitude, the more obvious was the negative effect of anoxic exposure on the sperm function of male adults. PMID- 17345767 TI - [Making of the animal model with sterilized testes]. AB - OBJECTIVE: To explore the methods of making an animal model with sterilized testes. METHODS: (1) X-ray local irradiation. Seventy 8-10-week-old male mice were equally divided into 6 experiment groups and a control group. The testes of the mice in the 6 experiment groups were irradiated sequentially by 1000, 1200, 1400, 1600, 1800 and 2000 cGy X-ray for 10 minutes, while those in the control group remained untreated. And then the pregnancy test was performed. (2) Cyclophosphamide injection. Forty 4-5-week-old male mice were divided into 3 experiment groups and a control group, the former treated with different doses of Cyclophosphamide via ip and the latter Natiichloridi Saline (N.S.) via i.p., followed by the pregnancy test. (3) Diphereline injection. Twenty 8-10-week-old male mice were equally divided into an experiment group and a control group, the former treated with Diphereline via ip and the latter N.S. via i.p., followed by the pregnancy test. (4) Identification by such pathologic examinations as TUNE1. technology, HE staining and immunohistochemical staining. RESULTS: (1) X-ray local irradiation. The male mice of Group 1 and 2 made their female partners pregnant respectively 10 and 15 days after the X-ray irradiation, but not those of Group 3 and 4 in our 3-month observation, and those of Group 5 and 6 died respectively 2 and 5 days after the X-ray irradiation. By comparison, the controls got their female partners pregnant within 3 days after placed together. (2) Cyclophosphamide injection. The male mice of Group 1 gained weight about 7 g and achieved pregnancy 9-14 days after drug termination, those of Group 2 gained around 4 g but failed to effect pregnancy, and those in Group 3 lost weight and died respective at 3, 4 and 5 weeks during the medication, while the controls all got their female partners pregnant within 3 days after put together. (3) Diphereline injection. The 10 male mice of the experiment group effected pregnancy 3 weeks after drug termination, while the 10 controls achieved the same result with 3 days after placed together. (4) Pathologic identification: TUNEL technology showed that apoptotic cells were occasionally seen (0.71 +/- 0.12)% in the testis tissue of the control group and remarkably increased (10.36 +/- 1.48)% in the model group, with significant difference between the two groups (P < 0.05). HE staining revealed normal testis tissues and convoluted seminiferous tubules with large numbers of germ cells in the control group, but atrophied convoluted seminiferous tubules and estranged cell linkage with only Ledig's cells but no germ cells in the model group. Immunohistochemical staining showed that the positive expression rates of CD29, Hsp90alpha and CD117 were respectively (50.30 +/- 5.2)%, (41.6 +/- 3.5)% and (73.6 +/- 3.7)% in the control group, as compared with (1.3 +/- 0.2)%, 0% and (1.6 +/- 0.3)% in the model group, with significant difference (P < 0.01). The positive expression rate of p53 was (19.7 +/- 0.8)% in the control group, significantly different from that of the model group, which was (39.4 +/- 2.9)% (P < 0.01). CONCLUSION: The animal model with sterilized testes can be made either by X-ray local irradiation of the testis or by Cyclophosphamide injection via i.p.. PMID- 17345768 TI - [Quantitative detection of DD3 mRNA in prostate cancer tissues by real-time fluorescent quantitative reverse transcription polymerase chain reaction]. AB - OBJECTIVE: To analyze the expression of DD3 mRNA in the prostate tissues. METHODS: DD3 mRNA was detected by realtime fluorescent quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR) based on the Taqman technique in the tissues of 27 patients with non-prostate cancer( NPCa), 21 prostate cancer( PCa), 39 benign prostatic hyperplasia (BPH) and 15 normal prostate (NP). The ROC curve was used to evaluate the diagnostic value of DD3 mRNA. RESULTS: DD3 mRNA expression was not detected in the NPCa tissues. The median expressions of DD3 mRNA in PCa, BPH and NP tissues were 7. 2 x 10(6), 2. 5 x 10(4) and 1.5 x 10(4) copies/mg tissue, respectively. The DD3 mRNA expression levels were significantly different between nonmalignant and malignant tissues (P < 0.01). No significant differences in DD3 mRNA expression were detected between the NP and BPH tissues and no significant correlation was found between the DD3 mRNA expression and clinical pathological parameters. The AUC-ROC was 0.937 (95% CI: 0.879 - 0.995) at cutoff value 1.4 x 10(5) copies/mg tissue. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio for DD3 were 90.5%, 85.0%, 86.7%, 76.0%, 94.3%, 6.03 and 0.11 respectively. CONCLUSION: The DD3 mRNA expression is confined to prostate tissues and highly upregulated in PCa tissues. It has a potential application value in the early diagnosis of prostate cancer and the follow-up of the patient. PMID- 17345769 TI - [Investigation of semen quality of 18-35 year old Chinese army men]. AB - OBJECTIVE: To investigate the semen quality of the Chinese army men. METHODS: Ten item sperm quality analyses were made by manual methods and the computer assisted sperm analysis system in 1054 young Chinese army men. The subjects were divided into 4 age groups (18-20 yrs., 21-25 yrs., 26-30 yrs and 31-35 yrs.), and the results of the analyses were compared. RESULTS: Among the 1 054 young males investigated, the semen volume was (2.6 +/- 1.4) ml, sperm density (55.9 +/- 46.5) x 10(6)/ml, sperm grade a + b motility (47.1 +/- 19.0)%, sperm viability (70.6 +/- 22.1)%, morphologically normal sperm (84.7 +/- 10.2)%, and acrosomal integrity (86.1 +/- 7.2)%. As for the percentages of the quality indexes that met WHO standards, the sperm volume was 73.5%, liquefaction time 91.1%, pH 93.0%, grade a + b motility 45.5%, viability 86.7%, sperm density 80.4%, morphologically normal sperm 98.2%, and the sperm total number 78.0%. Those who accorded with all the WHO standards accounted for 40.2%. CONCLUSION: The semen quality of the 18-35 year old army men was better than previously reported in the similar literature. And that of the 26-30 yrs. group was the best among all the age groups. PMID- 17345770 TI - [Potassium channel blocker regulates the proliferation of prostatic epithelial cells in SD rats]. AB - OBJECTIVE: To investigate the regulatory effect of potassium channel blocker (tetraethylammonium [TEA], aminopyridine [4-AP], glibenclamide [Glib]) on the proliferation of SD rat prostatic epithelial cells in vitro. METHODS: The primary culture was prepared by collagenase dissociation of minced prostatic tissues. Cells were cultured in serum-free prostate epithelial cell growth media and identified by immunocytochemical studies. TEA and 4-AP at the concentration of 1, 5 and 10 mmol/L and Glib at the concentration of 10, 50 and 100 mol/L were added, and after 24, 48 and 72 hours of culturing, a cell column diagram was drawn and the cell number counted. The post-passage cell growth was observed by MTT assay and Hoechst33258 nucleus staining. RESULTS: The cultured cells showed the typical morphological features of epithelia, with positive stain. MTT assay and Hoechst33258 staining showed that TEA, 4-AP and Glib at the increasing concentration effected different degrees of proliferation of prostatic epithelial cells after 24, 48 and 72 h (P < 0.01). CONCLUSION: The potassium channel blocker is a direct physiological regulator of the proliferation of SD rat prostatic epithelial cells. PMID- 17345771 TI - [Level of free L-carnitine in human seminal plasma and its correlation with semen quality]. AB - OBJECTIVE: To evaluate the difference of the free L-carnitine level in seminal plasma between fertile and infertile men and the correlation of free L-carnitine with semen quality, and to study the effect of L-carnitine on male fertility and its role in the evaluation and treatment of male infertility. METHODS: Semen samples of 230 infertile (normozoospermia, n=117, oligozoospermia, n=81, azoospermia, n=32) and 30 fertile men were collected and the level of free L carnitine in seminal plasma and such sperm parameters as sperm concentration, motility and vitality, were determined by high performance liquid chromatography and computer-assisted semen analysis system, respectively. The results were analyzed with the SPSS 12.0 software. RESULTS: The level of free L-carnitine in the seminal plasma of the fertile men was significantly higher than that of the infertile (P < 0.01). The lower the sperm concentration, the weaker the sperm vitality, the more significant the difference. The level of free L-carnitine in the semen was positively correlated with sperm concentration (r = 0.521, P < 0.001), and sperm motility (r = 0.319, P < 0.001) and vitality (r = 0.251, P < 0.001). CONCLUSION: The level of free L-carnitine in seminal plasma, significantly correlated with sperm concentration, motility and vitality, can be taken as a biochemical index used as a guidance for the clinical treatment of male infertility as well as for the study on the mechanisms of male reproduction. PMID- 17345772 TI - [Establishment of an animal model of azoospermia in male mice]. AB - OBJECTIVE: To establish a stable animal model of azoospermia in male mice. METHODS: Two groups of mice, with 30 in each, were intervened respectively by chemotherapy (intraperitoneal injection of Busulfan and Cyclophosphamide) and subcutaneous injection of Estradiol. At different times after the injection, the microscopic structures of the seminiferous tubules of both groups were observed and compared. The recovery of the germ cells in the seminiferous tubules was also evaluated after the termination of the intervention. RESULTS: A stable animal model was established by chemotherapeutic method with Busulfan and cyclophosphamide, while the model constructed by muscle injection of Estradiol was not stable. CONCLUSION: Compared with estrogen injection, chemotherapeutic intervention is a reliable method for constructing an animal model of azoospermia in male mice. PMID- 17345773 TI - [Comparison of transurethral surgical methods for treating small-size prostate hyperplasia]. AB - OBJECTIVE: To analyze different transurethral surgical methods for the treatment of small-size benign prostate hyperplasia (BPH) in order to improve the curative effect. METHODS: The clinical data of 52 cases of small-size BPH treated by transurethral surgery were reviewed and analyzed. Of the total number, 12 underwent transurethral prostate resection (TURP), 18 TURP plus transurethral incision of the bladder neck (TUIBN) and 22 TURP plus transurethral resection of the bladder neck (TURBN). The curative effect of the three different surgical methods was evaluated by international prostate symptom score (IPSS), maximum flow rate (Qmax) and post-voiding residual urine volume (PVR). RESULTS: In the TURP group, 3 cases were complicated with contracture of the bladder neck, and the IPSS, Qmax and PVR were (12.2 +/- 3.2), (11.7 +/- 2.6) ml/s and (27.6 +/- 13.0) ml, respectively. In the TURP + TUIBN group, there was only 1 case of the complication and the three indices were respectively (8.6 +/- 3.2), (16.7 +/- 3.0) ml/s and (20.0 +/- 8.0) ml. No complication was observed in the TURP + TURBN group and the three indices were (6.2 +/- 3.0), (22.7 +/- 3.1) ml/s and (8.0 +/- 4.0) ml, respectively. No statistical difference (P > 0.05) was found in IPSS, Qmax and PVR among the three groups before the operation, but significant difference (P < 0.01) was observed after it. The curative effect was better in the TURP + TUIBN group than in the TURP, but was the best in the TURP + TURBN. CONCLUSIONS: TURP + TURBN, being more effective than TURP + TUIBN, should be used as the first option for the surgical treatment of small-size BPH. The key to the operation is to thoroughly remove not only the hyperplastic gland but also the pathological changes of the bladder neck. PMID- 17345774 TI - [Interns' knowledge on male reproductive health: a comparison between pre- and post-training in the department of urology]. AB - OBJECTIVE: To investigate whether training in the department of urology will help interns acquire more knowledge on male reproductive health in such aspects as male erectile dysfunction (ED), premature ejaculation, male infertility (PE), male contraception, and so on. METHODS: Sixty interns receiving rotatory training in the Department of Urology of the Peking University Third Hospital were recruited to complete a questionnaire designed by ourselves. A comparison was made of their knowledge on male reproductive health before and after their training in the department by using the chi-square statistical test in SPSS 11.0 software. RESULTS: With regard to ED in such questions as "Do you regard ED as a disease affecting the aging male?" and "Do you regard ED as a local symptom of some male systemic disease?", all the interns knew significantly better after trained in the department of urology. Concerning the definition of ED and the effect of sildenafil citrate on ED, no significant difference was found in their knowledge between pre-training and post-training. As to patients' questions about ED, most of them showed interest but rarely made any initiative inquiries, which was not significantly changed after the training. Regarding PE, most of them knew very little even after trained, but they all thought of it as a disease affecting life quality. As regards male infertility, although some knew something about its definition and the normal parameters of semen routine analyses, others remained quite ignorant. As for male contraception, most of them knew little even after trained in the department. CONCLUSION: Interns generally acquire more knowledge on male reproductive health after trained in the department of urology. However, in regard to male infertility and male contraception, their knowledge is quite insufficient, which implies the need for strengthening the training in the related aspects. PMID- 17345775 TI - [Clinicopathological study of primary carcinoid tumor of the testis]. AB - OBJECTIVE: To study the clinicopathological characteristics, immunohistochemical features and histogenesis of primary testicular carcinoid tumor and its differential diagnosis. METHODS: Light microscopy and immunohistochemical stains were performed in 4 cases of primary testicular carcinoid tumor. RESULTS: The patients sought care for scrotum mass presented from 2 to 36 years, 2 cases accompanied with tender swelling of the testis. The tumors were described as nodular, yellowish-gray in color, 3.0-4.0 cm in the greatest dimensions, and well circumscribed, focal necrosis seen in 1 case. Histologically, they showed insular and trabecular patterns separated by fine fibrous bands. The tumor cells were round or polygonal with regular monomorphic nuclei, stippling chromatin and eosinophilic granular cytoplasm. There were rosette-like and tubuloglandular patterns with eosinophilic secretion in the cavity. Immunohistochemical staining for synaptophysin, chromogranin A, NSE and cytokeratin showed diffusely positive expression in the tumor cells. CONCLUSION: Primary testicular carcinoid tumor is extremely rare with good prognosis and its histogenesis remains controversial. Diagnostically it has to be differentiated from seminoma, metastatic carcinoid tumor, Sertoli cell tumor and granulosa cell tumor. PMID- 17345776 TI - [Percutaneous epididymal sperm aspiration: an effective diagnostic method for azoospermia]. AB - OBJECTIVE: To introduce the application of percutaneous epididymal sperm aspiration (PESA) in the differential diagnosis between obstructive and non obstructive azoospermia, and to investigate the association of the results of PESA with testis volume and the level of serum follicle stimulating hormone (FSH). METHODS: A total of 118 patients with diagnosed azoospermia were included. Their testis volume was measured by model method, the serum gonadal hormone level examined by chemoluminescence assay, and the epididymal fluid obtained by puncturing the head of the epididymis with a size-7 butterfly needle. RESULTS: Sperm was found in the epididymal fluid in 60 of the patients, 56 with normal and 4 with smaller testis volume, and 55 with normal and 5 with higher FSH level. No sperm was detected in the other 58 cases, 34 with normal and 24 with smaller testis volume, and 38 with normal and 20 with higher serum FSH level. The rate of successful PESA was significantly higher in patients with normal testis volume or normal serum FSH level than in those with smaller testis volume (P < 0.05) or higher serum FSH level (P < 0.05). CONCLUSION: PESA is a quick, convenient and effective method for the differential diagnosis between obstructive and non obstructive azoospermia. PMID- 17345777 TI - [CatSper and sperm hyperactivation]. AB - Elevation of sperm Ca2+ seems to be responsible for an asymmetric form of motility called hyperactivation, which is first seen near the time of fertilization. CatSper family proteins are putative cation channels expressed exclusively in the membranes of the sperm flagellum. Hyperactivation requires CatSper proteins, which presumably serve as the route of entry for Ca2+ that operates directly on the flagellar axoneme to increase waveform asymmetry. In this article, the structure of mouse CatSper, the role it plays in sperm hyperactivation and the unsolved problems are described. PMID- 17345778 TI - [Advances in the studies of epididymal protease inhibitor--Eppin]. AB - The epididymal protease inhibitor (Eppin) abounds in human semen and on the surface of human spermatozoa, specifically produced by the testis and epididymis. Recombinant Eppin has effected infertility in the immunized monkey and promises to be an effective vaccine for human immunocontraception. This article reviews the advances in the studies of Eppin gene and protein construction and its molecular mechanism of causing immunologic infertility and regulating PSA hydrolysis of Semenogelin. PMID- 17345779 TI - [Effects of insulin-like growth factor-1 on the regulation of hypothalamus hypophysis-testis axis]. AB - It has been demonstrated that insulin-like growth factor-1 (IGF-1) stimulates the proliferation and division of cells, facilitates the individual growth and development and regulates the material metabolism. Furthermore, it regulates male reproductive development and testicular endocrine functions. IGF-1 can stimulate the expression of GnRH gene in the hypothalamus of prepubertal male mice. However, it has no effect on or even inhibits GnRH gene expression in adult mice. IGF-1 may influence the growth, maturation and differentiation of GnRH neurons. It also accelerates LH and FSH secretion in hypophysis. IGF-1, produced locally in the testis and combined with its specific receptor, can regulate the proliferation and differentiation of adult Leydig cells, cause Sertoli cells to play different functions and control the biosynthesis of testicular hormones. PMID- 17345780 TI - [Correlation between traditional chinese medicine syndrome differentiation and urodynamic parameters in benign prostate hyperplasia]. AB - OBJECTIVE: To explore the correlation between the Traditional Chinese Medicine (TCM) syndrome differentiation and urodynamic parameters in benign prostate hyperplasia (BPH). METHODS: Urodynamic examination was conducted for 152 BPH patients, who were divided by TCM syndrome differentiation into seven types, namely, kidney-yin deficiency, kidney-yang deficiency, aqueduct stagnancy, spleen qi deficiency, lung-heat and qi stagnancy, wetness-heat down-flow and phlegm wetness stagnancy. RESULTS: Of the total number of the BPH cases, 71 (46.71%) were differentiated as the type of kidney-yang deficiency, 40 (26.31%) as aqueduct stagnancy, and 14 (9.21%) as kidney-yin deficiency. Fifty-eight cases of Grade III-IV bladder outflow obstruction fell into the type of kidney-yang deficiency, and another 38 cases of the same grade along with 26 cases of Grade V VI came under the type of aqueduct stagnancy. Of the 12 patients with very weak contractility of detrusor urine, 4 (33.33%) were attributed to the type of kidney yang deficiency and 7 (58.33%) the type of aqueduct stagnancy. Among the 48 with weak contractility of detrusor urine, 27 (56.25%) fell under the type of kidney yang deficiency and 17 (35.42%) the type of aqueduct stagnancy. CONCLUSION: The TCM syndrome differentiation of BPH is correlated with bladder outflow obstruction and detrusor urine contractility, which has provided corresponding evidence for the quantization and objectification of the TCM syndrome differentiation of BPH. PMID- 17345781 TI - Diuretics usage and future issues. PMID- 17345782 TI - ARBs or ACEIs, that is the question. PMID- 17345783 TI - Sympathetic overdrive and cardiovascular risk in the metabolic syndrome. AB - Sympathetic neural factors are involved in energy balance as well as in blood pressure control. This represents the background for the hypothesis that an adrenergic overdrive may be implicated in the development and/or progression of the metabolic syndrome. Indirect and direct markers of sympathetic drive have confirmed this hypothesis, by showing the occurrence of an adrenergic activation both at the cardiac and peripheral vascular level. It is likely that this sympathetic dysfunction is triggered by reflex mechanisms (arterial baroreceptor impairment), metabolic factors (insulin resistance), and humoral agents (angiotensin II, leptin). The adrenergic overdrive exerts a number of adverse effects on the cardiovascular system, by favoring the genesis of cardiac hypertrophy, vascular hypertrophy, arterial remodeling and endothelial dysfunction and thereby aggravating the already elevated cardiovascular risk profile of the patient. This carries obvious clinical and therapeutic implications, including the suggestion that sympathetic inhibition should be included among the goals of both pharmacological and non-pharmacological interventions employed in the treatment of the metabolic syndrome. PMID- 17345784 TI - Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor alpha. AB - The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes. PMID- 17345785 TI - Current usage of diuretics among hypertensive patients in Japan: the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study. AB - In the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study, we examined the current situation with respect to the prescription of diuretics, including the prevalence of diuretic treatment and the dosages used for patients with essential hypertension in primary care settings. Of the 3,400 hypertensive patients included in the study, 315 (9.3%) patients (mean age: 66.9+/-10.4 years; males: 43.5%) were prescribed diuretics. Compared with patients who were not using diuretics, those who were using diuretics were more obese and had more complications. The most commonly prescribed diuretic among the 331 prescriptions in the 315 diuretic users was trichlormethiazide (44%), followed by indapamide (15%) and spironolactone (14%). Among patients being treated with diuretics, monotherapy was used in only 5% of patients; in the majority of patients combination therapy including diuretics (95%) was used. Relatively low dosages of diuretics were generally used. There was a difference between the actual dosages prescribed and those recommended by the Japanese Society of Hypertension (JSH) guidelines or the product information approved in Japan. Compared with previous estimates of the prevalence of diuretic use in hypertensives in Japan (4.0-5.4%), the rate in the J-HOME study (9.3%) was higher. This may be attributable at least in part to the results of the many published, large-scale intervention trials confirming the clinical significance of diuretics. Although a relatively high dosage is recommended in the diuretic product information and in the JSH guidelines, dosages of diuretics should be reconsidered in Japan. PMID- 17345786 TI - Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. AB - Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2. PMID- 17345787 TI - Genetic influences of beta-adrenoceptor polymorphisms on arterial functional changes and cardiac remodeling in hypertensive patients. AB - Three subtypes of beta-adrenoceptor, beta1, beta2 and beta3, are involved in the sympathetic nervous system, which plays an important role in the development of hypertension and hypertensive complications. These complications can include left ventricular hypertrophy and arterial stiffness, which are reported risk factors for cardiovascular diseases. We designed clinical trials to clarify the association between hypertensive complications and beta-adrenoceptor single nucleotide polymorphisms in essential hypertension. Using Taqman PCR methods, we detected five polymorphisms of three beta-adrenoceptors: Ser49Gly and Arg389Gly for the beta1-adrenoceptor; Gly16Arg and Glu27Gln for the beta2-adrenoceptor; and Trp64Arg for the beta3-adrenoceptor. We included 300 subjects and measured pulse wave velocity, vasodilator response to hyperemia, left ventricular hypertrophy (by electrocardiogram and echocardiography), and cardiac enlargement (by chest X ray). We found that pulse wave velocity and nitroglycerin-induced hyperemia were both closely associated with the Ser49Gly polymorphism (p<0.05), and Glu27Gln was found by both electrocardiogram and echocardiography to be significantly associated with left ventricular hypertrophy (p<0.05). These data suggested that two polymorphisms of different beta-adrenoreceptor subtypes are the genetic influences on the development of arterial stiffness and left ventricular hypertrophy in essential hypertension. PMID- 17345788 TI - Clinical characteristics of aldosterone-producing microadenoma, macroadenoma, and idiopathic hyperaldosteronism in 93 patients with primary aldosteronism. AB - Primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is a form of surgically curable secondary hypertension, and distinguishing APA from idiopathic hyperaldosteronism (IHA) is important for treatment. We made a differential diagnosis between APA and IHA using imaging tests such as adrenal CT and MRI as well as adrenal venous sampling (AVS) in all 93 cases of PA presenting at our institutions over the last decade. We identified 27 patients with aldosterone-producing microadenoma (APmicroA), all of whom could be diagnosed by AVS but not by the imaging tests. Then, we compared the clinical and roent genological findings of these 27 patients with those of 42 patients with aldosterone-producing macroadenoma (APmacroA) and of 24 patients with IHA. Using surgically removed adrenal tissues, histopathological examinations and immunohistochemical analyses of steroidogenic enzymes were conducted. The findings for APmicroA were similar to those for APmacroA, except with respect to the diameter of the adrenal adenomas. Endocrinological and roentgenological findings for APmicroA were similar to those for IHA, but not to those for APmacroA. The rate of cure of hypertension was much greater in patients with APmicroA than in patients with APmacroA after the unilateral adrenalectomy (odds ratio, 4.0; p=0.028). In conclusion, it is important to accurately diagnose APmicroA, in which the laterality of the hyperproduction of aldosterone is only detectable by AVS, and to treat these patients by unilateral adrenalectomy in order to avoid long-term medical treatment and prevent hypertensive vascular complications. PMID- 17345789 TI - Relationship between metabolic syndrome and Trp64arg polymorphism of the beta adrenergic receptor gene in a general sample: the Shigaraki study. AB - It has been reported that the beta3-adrenergic receptor gene (ADRB3) is associated with abnormal metabolic risk factors. Therefore, we examined whether the Trp64Arg polymorphism of ADRB3 affects the occurrence of metabolic syndrome (MS). The participants were 2,395 subjects who underwent a medical examination in Shigaraki in Shiga, Japan. Among them, 1,416 subjects who gave informed consent for genetic analysis and were not receiving treatment for hypertension, diabetes, or hyperlipidemia were enrolled in this study. MS was diagnosed in 86 (16.0%) of 537 men, and 8 (0.9%) of 879 women. There was no significant relationship between ADRB3 polymorphism and the frequency of MS. Multiple logistic regression analysis including smoking, sex, and age as confounding factors showed no interaction between MS and ADRB3 polymorphism (odds ratio: 0.94; 95% confidence interval: 0.59-1.49; p=0.78). Subjects were also analyzed according to differences in the number of abnormal metabolic risk factors. However, there was no significant relationship between ADRB3 polymorphism and the number of such factors. In conclusion, in a general sample, the frequency of MS was 16.0% in men, and 0.9% in women. There was no relationship between ADRB3 polymorphism and MS. PMID- 17345790 TI - Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome. AB - The purpose of the present study was to elucidate the cardiac structure and function in patients who have metabolic syndrome but no history of cardiovascular disease by analyzing echocardiographic findings. Echocardiographic examination was performed to screen for cardiovascular disease in 135 patients who were in their sixties. Patients were divided into metabolic syndrome (n=65, age: 65+/-2.7 years) and non-metabolic syndrome (n=70, age: 66+/-2.5 years) groups based on the criteria for metabolic syndrome proposed by the Japanese Society of Hypertension and seven other societies in 2005. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial filling (A velocity), and the ratio of E to A (E/A) was assessed by the transmitral flow. The Tei index, which reflects both LV diastolic and systolic function, was also calculated. There were no differences in relative wall thickness, LV mass index, or LVEF between the two groups. However, both the EIA and Tei index were significantly different between the metabolic syndrome (0.66+/-0.14 and 0.36+/-0.07, respectively) and non-metabolic syndrome (0.88+/-0.25 and 0.29+/-0.09) groups (p<0.001). These results indicate that patients with metabolic syndrome can have cardiac diastolic dysfunction even if they have neither LV hypertrophy nor systolic dysfunction. PMID- 17345791 TI - Oral pretreatment with ebselen enhances heat shock protein 72 expression and reduces myocardial infarct size. AB - Reactive oxygen species (ROS) enhance myocardial ischemia-reperfusion (I/R) injury. Ebselen, a seleno-organic glutathione peroxidase (GPx) mimetic, has a protective effect against tissue injury induced by ROS. However, the cardio protective effect of orally administered ebselen has never been investigated in cardiac I/R injury. We investigated the effects and mechanisms of orally administered ebselen on experimental myocardial infarction. Isolated perfused rabbit hearts underwent 30 min of global ischemia and 60 min of reperfusion, with or without oral administration of ebselen 24 h before I/R, with or without enhanced oxidative stress by H202 infusion for the first 1 min of reperfusion. The recovery of left ventricular developed pressure (LVDP) was significantly improved, and the myocardial infarct size was significantly reduced by ebselen. The recovery of LVDP and the myocardial infarct size were markedly aggravated by H202 infusion. These enhancements by H202 were dose-dependently suppressed by ebselen, along with a reduction in myocardial 8-hydroxydeoxyguanosine levels, a marker for oxidative DNA damage. The myocardial reduced glutathione (GSH) level was preserved by ebselen. Ebselen markedly enhanced myocardial heat shock protein (HSP) 72 expression. The cardioprotective effect of ebselen-induced HSP72 was confirmed by MTT assay in isolated cardiomyocytes using KNK437, a novel HSP inhibitor. In conclusion, an oral administration of ebselen 24 h before I/R provided excellent cardioprotective effects, at least in part through HSP72 induction and GSH preservation. PMID- 17345792 TI - Allopurinol reduces neointimal hyperplasia in the carotid artery ligation model in spontaneously hypertensive rats. AB - Uric acid and oxidative stress promote cardiovascular diseases, including atherosclerosis and hypertension. Xanthine oxidase, through which uric acid is generated, is a free-radical generating enzyme. The aim of the current study was to investigate whether allopurinol, an inhibitor of xanthine oxidase activity, affects vascular remodeling and vascular smooth muscle cell (VSMC) proliferation. In the carotid artery ligation model using spontaneously hypertensive rats (SHR), treatment with allopurinol induced a reduction in the neointima/media ratio by 27% (38.5+/-34.3% in the control group and 28.1 20.8% in the allopurinol-treated group, respectively, p<0.01) without alterations in vascular circumference at 3 weeks after ligation when compared to the control. Allopurinol lowered the serum uric acid concentration (147.0+/-3.6 micromol/l in the control group and 16.1+/ 3.6 micromol/l in the allopurinol-treated group, respectively p<0.01) and xanthine oxidase activity, but not the blood pressure. In an in vitro study, high concentrations of uric acid (100 and 200 micromol/l) stimulated VSMC growth, but there was no stimulation of these cells by a low concentration of uric acid (50 micromol/I) or by any of three concentrations of xanthine (50, 100 and 200 micromol/l). In addition, allopurinol (5 micromol/I) had no effect on the cell growth. In conclusion, uric acid is a potent stimulator of VSMC proliferation, and allopurinol prevented vascular remodeling in SHR at least in part by inhibiting uric acid concentration. PMID- 17345793 TI - Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats. AB - We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells. PMID- 17345794 TI - [Choroidal neovascularization---physiopathologic theories]. AB - The Age-Related Macular Degeneration is an extremely serious health problem for the elderly people. The therapeutic options are not so effective, but there are a plenty of physiopathologic theories and hypothesis for logical epidemiology and etiology. We are looking through this theoretical aspects and try to identify what is necessary for clinical practice. PMID- 17345795 TI - [Aqueous humour elimination, uveoscleral pathway--morphologic and morpho pathologic considerations]. PMID- 17345796 TI - [Retinal vasculitis]. AB - Inflammation involving the retinal vasculature may occur as an isolated finding unrelated to an identifiable underlying diagnosis, termed primary retinal vasculitis, or may be associated with a myriad of both ocular and systemic pathology. Retinal vasculitis is most accurately defined as vascular leakage and staining of vessel walls on fluorescein angiography, with or without the clinical appearance of fluffy, white perivascular infiltrates in the eye with evidence of inflammatory cells in the vitreous body or aqueous humor. Management of retinal vasculitis requires a dualistic approach: one, to control ocular inflammation and reverse a potentially sight-threatening condition, and two, to spare no effort in identifying and treating concomitant, and in many cases, life- threatening systemic disease. PMID- 17345797 TI - [Choroidal melanoma in a patient with type I neurofibromatosis]. AB - The authors present the case of a male patient with neurofibromatosis type 1 associated with choroidal malignant melanoma. We present the difficulties of the differential diagnosis and the rapid and aggressive evolution of the intraocular tumor. PMID- 17345798 TI - [Toxic anterior segment syndrome]. AB - The authors present two cases of TASS which occurred consequent upon anterior chamber administration of cefuroxime(Axetin). The ESCRS guidelines on prevention, investigation and management of postoperative endophthalmitis recommends intracameral injection of an antibiotic agent (cephalosporin) at the conclusion of surgery. In our group of patients TASS occurred. Elements of diagnosis and treatment in TASS are discussed. As a conclusion to our study we decided to discontinue cefuroxime administration. PMID- 17345799 TI - [The value of angiofluorography in serous central retinopathy diagnosis]. AB - Central serous retinopathy is a disease of young and middle-age male in which the fluorescein angiography (FA) can be useful for the diagnosis of certainty, especially for the cases with chronic evolution. The method can be used for the exclusion of other diseases with similar clinical appearance. This work shows a few cases of disease for that the FA was performed to certificate the diagnosis. PMID- 17345800 TI - [Fungal keratitis--diagnostic and therapeutic approach]. AB - INTRODUCTION: Fungal keratitis is one of the most difficult corneal infections to be properly diagnosed and treated. PURPOSE: Diagnostic and therapeutic approaches in atypical keratitis, regarding a case. MATERIAL AND METHOD: The paper presents a case of stromal fungal keratitis successfully treated with topical amphotericin B 0,2% and natamycin 5%. The clinical appearance and the indolent course directed the diagnosis, the micro-biological analysis of corneal scrapings being negative. Further on, there are presented the laboratory investigations and the available antifungal agents, because proper therapy early in the course of the disease can be crucial to a successful outcome. CONCLUSIONS: Clinical suspicion of fungal keratitis is essential to diagnosis, but once the diagnosis is made, the treatment remains difficult. Direct microscopic examination of corneal tissues using specific stains is a very useful and inexpensive method of diagnosis, being conclusive in 80% of cases. PMID- 17345801 TI - [Kerato-mycosis--case report]. AB - The authors present the case of mycotic keratitis caused by Candida spp. PMID- 17345802 TI - [Correction of myopia with excimer laser Carl Zeiss Meditec MEL 70--Lasik technique]. PMID- 17345803 TI - [Comparative results of nonpenetrante profound sclerectomy converted in trabeculectomy with standard trabeculectomy]. PMID- 17345804 TI - [Amniotic membrane transplantation in palliative treatment of bullous keratopathy]. AB - PURPOSE: To assess the efficacy of amniotic membrane transplantation for the improvement of symptoms in bullous keratopathy. MATERIAL AND METHOD: Prospective study. 14 patients were operated between 01.02.2003 - 01.02.2006. the follow-up period: between 6 and 42 months with an average of 18 months. The following parameters were evaluated: corneal re-epithelialisation appearance of epithelial bullae, pain, photophobia. RESULTS: In 11 cases there was an improvement of the symptomatology: complete in 8 cases and partial in 3 cases. CONCLUSIONS: Amniotic membrane transplantation is an efficient palliative treatment for bullous keratopathy. PMID- 17345805 TI - [The tear crystallization test in sicca syndrome]. AB - The tear crystallization test permits an easy and quick identification of the lacrimal film alterations existent in the Sicca syndrome. From the 29 crystallization tests done on patients suffering from Sicca syndrome medium and severe form the most frequent was type III crystallization (21 cases-73%), type IV (4 cases-14%) and type I (1 case-3%). Type III and type IV of crystallization occurs in 87% of patients with Sicca syndrome in correspondence with the intensity of the dry-eye symptoms and with the objective qualitative and quantitative tests of the lacrimal film and corneo-conjunctival surface examination (Schirmer test I, BUT, rose bengal 1%, fluorescein 19%). The correlation between subjective and objective modifications is necessary in the Sicca syndrome. Although 26% of the patients diagnosed with Sicca syndrome accused severe dry eye symptoms, only 14% presented type IV crystallization. The absence of crystallizations has been revealed in superficial punctate keratitis (1 case), Sicca keratoconjunctivitis (1 case), filamentary keratitis (1 case), superficial punctate keratitis and corneal ulcus (1 case). PMID- 17345806 TI - [Lacrimal proteins electrophoretic analysis--diagnostic method in secondary Sjogren syndrome]. AB - PURPOSE: We analysed and compared electrophoretic tear protein patterns of healthy subjects and patients with different autoimmune diseases associated with secondary Sjogren's syndrome. MATERIALS AND METHODS: Tears were collected using the Schirmer's method. Proteins were separated by sodium-dodecyl sulfate poliacrylamide gel electrophoresis. The lanes were stained by Coomassie blue and/or silver. RESULTS: Lactoferrin, albumin, lipocalin and lysozyme were found to be the main components being identified using molecular weight markers. CONCLUSIONS: Electrophoretic analysis of tear proteins patterns is a fast, reproducible and simple method which provides information about the possibility of lacrimal gland involvement in autoimmmune diseases. PMID- 17345807 TI - [Intraorbital tumoral pathology in adults--5 years of experience in Bagdasar Arseni Hospital Bucharest]. AB - The purpose of this issue is a retrospective analysis of the intraorbital tumoral pathology at adults, who were hospitalised, investigated and treated during 5 years, 1999-2004, in neurosurgery departments of the Clinical Emergency Hospital "Bagdasar-Arseni", Bucharest. The authors wish to point out the importance and usefulness of interdisciplinary co-operation, where the ophthalmologist succeed to harmonize the professional contribution of neuro-radiologist, neurosurgeon and pathologist for the sake and benefit of the patient. PMID- 17345808 TI - [Intraocular irrigating solutions during phacoemulsification and corneal changes]. AB - This study evaluate the number, density and quality of endothelial cells of the cornea during phacoemulsification when several sterile intraocular irrigating solutions are used. PMID- 17345809 TI - [Matrix-metalloproteinases and glaucoma]. AB - PURPOSE: To analyze the matrix-metalloproteinases' activity (MMP-2 and MMP-9) in primary open angle glaucoma patients with indication for filtrating surgery. METHODS: A prospective study, 8 months, in the Ophthalmology Department of the Central Military Hospital, with the collaboration of "Victor Babes" Institute. The study was conducted on 27 eyes with primary open glaucoma and that have underwent filtrating surgery. Patients with other ocular or systemic associated conditions were excluded. Patients were distributed in 3 groups, according to their topical treatment with prostaglandin analogs: Group A: 11 eyes with travoprost 0,004%. Group B: 9 eyes with latanoprost 0,005%. Group C: 7 eyes without prostaglandin analogs. The fragments collected during surgery were processed for imunohistochimical analysis for MMPs. It has used the indirect tristadial method: streptavidine-biotin-peroxidase. PMID- 17345810 TI - [Protein C reactive and glaucoma]. AB - PURPOSE: To observe the possible implications of the C reactive protein in pathogenesis of the glaucoma. METHODS: A clinical observational prospective study on 2 groups: group A 14 glaucomatous patients and group B--control (12 normal subjects) without history of ocular pathology or general pathology known to be associated with high plasma levels of CRP. The groups were homogeneous about the age and sex distribution. CRP levels were evaluated by tests with high specificity. RESULTS: The plasma CRP level reveals important differences (p < 0,0001) on the two groups: 3,87 +/- 0,8 mg/dl in the group A and 0,68 +/- 0,13 mg/dl in the control group. CONCLUSIONS: Glaucoma is associated with high plasma levels of CRP. In the complex pathogenesis of glaucoma, in which the vascular factor has his well known place, the inflammatory vascular modifications may represent an important component. PMID- 17345811 TI - [Refractive stability of foldable intraocular lenses]. AB - PURPOSE: To compare the refractive stability of different kind of foldable intraocular lenses. METHOD: There was performed a two years (mean follow-up 7,4 +/- 1,2 months) prospective interventional case series study on 108 with senile cataract, without another ocular pathology which underwent cataract surgery by phacoemulsification and implantation of foldable intraocular lens (the same surgeon). Each patient had their refractive status measured at the 1-month postoperative visit, 3-months and at the 6-months follow-up visit. The results have been statistically analyzed using the Wilcoxon test. RESULTS: The postoperative refractive results were correlated with IOL design and material. The acrylic hydrophobic foldable intraocular lens with rigid haptics was more likely to move to hypermetropia and the acrylic hydrophobic foldable intraocular lens with pliable haptics showed minimal myopic movement. CONCLUSIONS: On long term, the 1-piece acrylic hydrophobic IOL with soft acrylic loops had the most stable refractive results. PMID- 17345812 TI - Intraocular foreign bodies associated with traumatic cataract. AB - OBJECTIVE: To determine prognostic factors and visual outcomes in patients with intraocular foreign bodies (IOFBs) associated with traumatic cataract. PARTICIPANTS: 19 patients undergoing surgical removal of IOFB and cataract extraction with a minimum of 6-months follow-up. OUTCOME MEASURES: Final best corrected visual acuity was the main outcome where ocular findings at presentation were compared with final visual acuity to determine prognostic factors for visual outcome. RESULTS: Final best corrected visual acuity of > 6/30 was obtained in 12 patients (63.2%) and functional vision (> 1.5/60) was achieved in five patients (26.3%). CONCLUSION: Final visual outcomes were found in 63.2% of patients. Initial visual acuity was the strongest predictor of final visual outcome in this study. Additional predictive factors included the mechanism of injury and the presence of vitreous hemorrhage. PMID- 17345813 TI - [Neovascularization in rat optic nerve]. AB - The study aims at assessing possible age-induced alterations in the nervous vascular network by examining the microcirculation of the optic nerve in rats grouped by age. Histological specimens were stained with hematoxiline-eosine, the Romhany-Barzu dye staining and the Gomory tri-chromic dye staining. The volume, section surface and total surface of 2-6 micro and 7-14 micro vessels were determined on a total of 960 vessels of this group, over a five square millimeter area. The tables show the increase of vascular parameters from birth to adulthood, and the fact that not all the vessels were injected in old animals. The density of the vessels per square millimeter, their average length and average diameters, error calculus, variation coefficient, Student test and chi2 allow assessing the differences between animals belonging to the same species but to different age groups, or under the influence of medication. PMID- 17345814 TI - [Viruses and the immune system (editorial)]. PMID- 17345815 TI - [Quality of life in patients with chronic renal failure]. AB - INTRODUCTION: Hemodialysis and transplantation are performed not only to replace renal function, but also to improve patients' quality of life. The aim of our investigation was to compare the quality of life in patients with chronic renal failure (CRF) before and after the introduction of active therapy. MATERIAL AND METHODS: We tested 76 patients (pts): 20 pts on conservative therapy (CT), 21 pts on chronic hemodialysis and 35 pts with renal transplantation. A questionnaire (combining two questionnaires) was used to investigate the physical, emotional and social aspects of health. RESULTS: In regard to physical health of transplantation patients (TP) it was established that work capacity and activities were less damaged, whereas physical activity was highest in pts on CT. Social activity was limited in a higher percentage in TP (40%) than in hemodialysis patients (HD) (19%), while family relationships were most damaged in pts on HD (28.57%). Discomforts were most common in pts on HD. The highest percentage of pts estimated their health status as good or average, but their health status improved after transplantation in 82.86% that is in 57.14% after HD. It was similar with the quality of life: 28.57% of kidney transplant patients rated their quality of life as very good, and 54.28% rated it as good: 38.09% of HD patients rated their quality of life as very good, whereas only 5% of CT patients rated it as very good, and 20% as good. PMID- 17345816 TI - [Efficacy and safety of peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C virus infection]. AB - INTRODUCTION: Chronic hepatitis C remains a formidable threat to world health. Progression of chronic hepatitis C is associated with significant morbidity: cirrhosis, hepatic failure and hepatocellular carcinoma. The introduction of combined therapy with pegylated interferons and ribavirin has increased the sustained virologic response (SVR) in the much higher percentage than with previous treatment options, while the level of adverse effects has not changed significantely. The aim of this study was to assess the efficacy and safety of combined therapy (peginterferon alfa-2a + ribavirin) in Serbian population. MATERIAL AND METHODS: Patients with genotypes 1 and 4 received a 48-week course of therapy of peginterferon alfa-2a (180 microg/week) and ribavirin (1000-1200 mg/day). Patients with genotypes 2 and 3 received the same doses of both drugs, but during 24 weeks. All patients were scheduled for follow-up visit 24 weeks after the end of treatment. Physicians were instructed to adjust the dose of both drugs if adverse events occurred. Standard PCR tests were used for qualitative and quantitative detection of viral RNA, as well as for determination of patients' genotypes. RESULTS AND DISCUSSION: A total of 95 patients were enrolled in the sutdy. The majority of patients were male (65.26%), aged 40 or under (52.63%), with genotype 1 (63.15%). The average duration of infection was 2.81 + 4.89 years, but still, the majority of patients (51.58%) had HCV infection for less than 2 years. Fibrosis was present in 69.47 % of patients, and cirrhosis in 21.06%. The most common mode of infection was through i.v. drug use (29.48%), but it was unknown in 32.63% of patients. The mean ALT value was 100.44 + 70.26, with the total of 93.68% of patients having elevated ALT level. At the end of treatment (EoT) time point, data were collected from 66 patients (69.47%), while at the end of follow-up (EoFU), data were collected from 68 patients (71.58%). This unusuall drop-out rate of 28.42% was mainly caused by losing contact with patients (14.74%) and premature termination of therapy (13.68%). The primary parameter of efficacy SVR at the EoFU was achieved in 59 out of 68 patients (86.76%), while the secondary efficacy parameter (SVR at the EoT) was achieved in 77.27% of patients. Multiple regression anlysis has established the initial level of ALT, patient's age and fibrosis level as main parameters statistically significantely impacting the outcome of treatment. Although without statistical significance, the trend of better outcomes was associated with early therapy (within 2 years from infection), and while the disease has not progressed (patients with fibrosis achieved SVR at the EoFU in 89.19% vs. 75.00% in patients with cirrhosis). The safety record was good, the most common adverse effects including cytopenia, rash and local reactions at the site of administration. CONCLUSION: Combination therapy with peginterferon alfa-2a and ribavirin is safe and well tolerated, with SVR achieved in 86.76% of patients. PMID- 17345817 TI - [Correlation between radiological and clinical findings after anterior cruciate ligament reconstruction]. AB - INTRODUCTION: In the last two decades, the gold standard for anterior cruciate ligament reconstruction is the bone-patellar tendon-bone graft procedure. Correct position of the bone-patellar tendon-bone graft significantly affects the postoperative knee stability. The aim of this study was to establish if and how clinically measured knee stability is associated with radiographic position of bone-patellar tendon-bone graft in the femoral and tibial bones. MATERIAL AND METHODS: The prospective study included 39 patients, 30 men and 9 women. We analyzed and compared results of clinical and radiographic examinations prior to and 2 years following surgery. RESULTS: The mean arthrometric difference between the anterior tibial movement prior to surgery was 11.2 mm and 2.4 mm (p < 0.05) after surgery. The preoperative Tegner and Lysholm score was 1.49, and postoperative 8.23 (p < 0.05). The preoperative Lysholm-Gillquist scale was 51.56 and postoperative 97.74 (p < 0.05). The International Knee Documentation Committee (IKDC) scores were as follows: grade A in 32 patients (84.6%), grade B in 5 patients (12.8%), and grade C in 1 patient (2.6%). By comparison of IKDC scores and radiographic parameters (M1-M10) of anterior-posterior and profile views, a statistical significance was found only between IKDC and M9 index (sagittal femoral index OR'/RR' x 100). DISCUSSION: By using bone-patellar tendon bone grafts, it is not possible to entirely achieve anatomical positions. Correct graft position within the bone tunnels is of great significance concerning knee stability after anterior cruciate ligament reconstruction. CONCLUSION: Correlation between radiological and clinical findings after anterior cruciate ligament reconstruction in our 39 patients shows that only the position of the graft affects the clinical outcome. Posterior graft location provides better clinical outcome and knee stability. On the other hand, anterior location is associated with worse postoperative IKDC scores, unstable knee and worse clinical outcome. PMID- 17345818 TI - Effects of Alendronate on bone mass in women with osteoporosis. AB - This paper presents the results of a two-year study of the effects of alendronate (Fosamax) on bone mass in 187 women with osteoporosis, mean age 57.68 years. Bone mass, i.e. bone mineral density (BMD) was measured at the lumbar spine. Measurements were performed prior to treatment, one year and two years after treatment using the DEXA method. The BMD was examined in 65 women, mean age 54.02, taking calcium and vitamin D, and in 75 women mean age 57.16, without any therapy. The baseline BMD (T score) in the alendronate group was -2.87 SD, whereas in the two control groups it measured -1.86 SD and -2.02 SD, respectively. A significant improvement of bone mass, by 5.8%, was registered after a year of treatment with alendronate, and by 8.3% after two years. In patients receiving calcium and vitamin D, a significant increase of bone mass was established as well: by 2.9% after a year, but the values declined back to the baseline after the second year. In patients without any treatment the bone mass decreased by 0.6% after a year, and by 0.9% after the second year. PMID- 17345819 TI - [Effects of new nitric oxide synthase inhibitors on spontaneous locomotor activity]. AB - INTRODUCTION: New nitric oxide synthase (NOS) inhibitors: 3-bromo-7-nitroindazole (3-Br-7-NI), 1-(2-trifluoromethylphenyl) imidazole (TRIM), S-methyl-L thiocitrulline (S-Me-TC) and 7-nitroindazole (7-NI) reduce spontaneous locomotor activity in mice. MATERIAL AND METHODS: In order to elucidate central effects of NOS inhibitors on locomotor activity, the influence of 7-NI on electroencephalographic (EEG) power spectrum in rats was investigated. RESULTS: 7 NI reduced the EEG power density in all frequency bands in rats, suggesting a depression of the central neuronal activity. The electrophysiologic power was most reduced in the range of 7-9 Hz of the rhythmic slow activity (theta rhythm), which is in accordance with decreased locomotor activity observed following administration of NOS inhibitors. CONCLUSION: The present results indicate that nitric oxide exerts an excitatory effect on central neuronal structures involved in regulation of locomotion. PMID- 17345820 TI - [Epistaxis in patients with hereditary hemorrhagic teleangiectasia]. AB - INTRODUCTION: Spontaneous recurrent epistaxis is the most common clinical manifestation of hereditary hemorrhagic teleangiectasia (HHT). It occurs in more than 90% of HHT patients and is the most distressing symptom. Nasal teleangiectasias tend to increase with age both in size and number, so epistaxis is heavier and more frequent. For patients with mild to moderate disease, there are many adequate treatment options. For those with severe disease, most treatments offer just a hemorrhage-free interval. Experienced otorhinolaryngologists who treat epistaxis in these patients often use the adage "to do as little as possible for as long as possible". MANAGEMENT OF ACUTE EPISTAXIS: The recommendations for the management of acute epistaxis include: compression, use of topical antifibrinolytics, laser therapy, argon plasma coagulation therapy, fibrin sealant spray or gelatin sponge soaked in adrenaline. In cases of heavy acute epistaxis, an epistaxis balloon combined with artery ligation and/or embolization is the most effective treatment. Nasal packing and electrocauterisation should be avoided to prevent further trauma to the blood vessels. TREATMENT OF RECURRENT EPISTAXIS: Management of recurrent epistaxis includes topical application of laser energy (argon, Nd:YAG, KTP/532 and diode, not CO2), argon plasma coagulation in combination with 0.1% estriol ointment, caustics, antifibrinolytics, bleomycin and sclerosing substances. Systemic estrogen-progesterone at doses used for oral contraception may eliminate bleeding in women with heavy epistaxis. Systemic antifibrinolitics (used with extreme precaution) and septal dermoplasty give good results. The only method which successfully and permanently solves the problem of severe refractory epistaxis in hereditary hemorrhagic teleangiectasia is closure of the nasal cavities. PMID- 17345821 TI - [Neurosurgical treatment of pain]. AB - INTRODUCTION: Surgical treatment of chronic pain includes destructive procedures (neurectomy, rhizotomy, sympathectomy), often referred to as ablative, and accompanied by high morbidity and mortality rates. SURGICAL TREATMENT OF PAIN: During the past three decades, thanks to current knowledge on chronic pain mechanisms and technological developments, such as improved microsurgical and stereotactic techniques, guided by computerized tomography, magnetic resonance imaging and neural tissue impendance monitoring, the majority of ablative procedures have been replaced by new methods. Among them, a few can be considered as selectively and minimally ablative (microsurgical spinothalamic cordotomy, dorsal root entry zone lesions, limited midline myelotomy) and others as neuroaugumentative procedures for neuromodulatory proceses (deep brain structures and spinal cord stimulation, drug-delivery systems). NEUROSURGICAL PROCEDURES: Cordotomy is very effective in pain treatment and it may produce complete abolishment of pain, especially in patients suffering from neoplastic invasion of the brachial plexus (Pancoast's syndrome) or lumbosacral plexus. Dorsal root entry zone operation is generally the only treatment option for pain due to root avulsion and segmental pain in spinal cord injury. Spinal cord stimulation is useful in management of pain following peripheral nerve injury. Deep brain stimulation is a promising treatment of central pain. CONCLUSION: The purpose of this review is to draw attention to neurosurgical approaches to treatment of chronic and opioid-resistant pain. PMID- 17345822 TI - [Low back pain and degenerative disc disease]. AB - INTRODUCTION: Various clinical conditions can cause low back pain, and in most cases it is of a degenerative origin. Degenerative disc disease is a common condition which affects young to middle-aged men and women equally. Changes in the mechanical properties of the disc lead to degenerative arthritis in the intervertebral joints, osteophytes, and narrowing the intervertebral foramen or the spinal canal. PATHOPHYSIOLOGY: Degenerative cascade, described by Kirkaldy Willis, is the widely accepted pathophysiologic model describing the degenerative process as it affects the lumbar spine in 3 phases. DIAGNOSIS: There are two forms of low back pain secondary to degenerative disc disease: a) lumbalgia and b) lumbar radiculopathy. Limitation of movement, problems with balance, pain, loss of reflexes in the extremities, muscle weakness, loss of sensation or other signs of neurological damage can be found on physical examination. For accurate diagnosis, it is often necessary to combine clinical examination and sophisticated technology. TREATMENT: Coservative treatment consists of rest, physical therapy, pharmacological therapy and injection therapy. Physical rehabilitation with active patient participation is a key approach to treatment of patients with discogenic pain. Physical therapy, occupational therapy and kinesitherapy are important for improving muscle strength, endurance, and flexibility. Disc surgery is performed if surgical intervention is required. PMID- 17345823 TI - Tension-free vaginal tape obturator system in the treatment of stress urinary incontinence. AB - Surgical approach to the treatment of female stress urinary incontinence has changed significantly since 1995, when Ulmsten first described the procedure providing tension-free support in the middle part of urethra. Although retropubic placement of TVT tapes seemed to meet all the standards of minimally invasive surgical procedures, the occurrence of complications (bleeding, hematomas, and bladder, urethral of intestinal injuries) necessitated a new obturator approach. This study presents a transobturator approach to TVT tapes placement (Gynecare, Johnson-Johnson Company) with "inside-out" technique, first shown by De Leval in 2003. During 2005, 6 TVT tapes for stress urinary incontinence treatment were placed at the Clinic of Gynecology and Obstetrics in Novi Sad without any intra or post-operative complications. PMID- 17345824 TI - [Learning curve in performing radiofrequency ablation of accessory pathways in patients with Wolf-Parkinson-White syndrome]. AB - INTRODUCTION: This study examines the effect of operator experience on radiofrequency ablation (RFA) of accessory pathways success rate in patients with Wolff-Parkinson-White (WPW) syndrome. MATERIAL AND METHODS: The first 100 consecutive patients with WPW syndrome treated by radiofrequency ablation at our Clinic, were divided into group A (first 50 patients) and group B (the following 50 patients). Various parameters were compared between these 2 groups. RESULTS: The success rate in group A was 69% and in group B 92%, p < 0.01. There were 6 patients with recurrent WPW syndrome, after 3 months of follow-up, 5 were from group A and 1 from group B, p < 0.05. Significantly more applications of radiofrequency energy were delivered in group A (10.0 +/- 4.8 in group A and 6.2 +/- 3.1 in group B, p < 0.05). Two patients from group A presented with complications: one had intermittent complete AV-block, and the other pericardial effusion. CONCLUSION: This study shows a clear learning curve in performing RFA of accessory pathways in patients with WPW syndrome. PMID- 17345825 TI - [Results of autovenous femoro-distal bypass procedures in the type III peripheral obliterative arterial disease of the extremities in diabetic and nondiabetic patients]. AB - INTRODUCTION: It has been established that infrainguinal occlusive disease, type III peripheral obliterative arterial disease (POAD), is more common in diabetics than in non-diabetics. It is presumeable that after surgical treatment of this arterial segment diabetics develop more complications and higher mortality rate than non-diabetics. The aim of this study was to analyze the results of reconstructive surgical treatment of diabetic and non-diabetic patients with type III PAOD. MATERIAL AND METHODS: In the period 1999-2003, 118 patients with Type III PAOD underwent surgery at the Vascular Surgery Clinic in Novi Sad. They were divided into two groups: group I included 51 nondiabetic patients, and group II 67 diabetic patients. Subgroups were formed based on the clinical status. Differencies were established in IVa, (46 diabetics and 4 non-diabetics) and IVb stage (11 diabetic and 30 non-diabetic patients). RESULTS: Statistical data analysis using X2 test showed a stastical difference in complications rates, number of salvaged limbs and finally, in the mortality rates between diabetic and non-diabetic patients. CONCLUSION: Diabetic patients presented with significantly more trophic lesions (IVa stage). The overall complication rate was significantly higher in diabetics, as well as the amputation rate. Finally, the mortality rate was also significantly higher in diabetics than in nondiabetic patients. PMID- 17345826 TI - [The use of low molecular weight heparins in patients with acute ST-elevated myocardial infarction]. AB - INTRODUCTION According to the published guidelines for the management of acute coronary syndromes (ACS), treatment of acute ST-elevated myocardial infarction is based on rapid revascularization, either mechanical or pharmacological. Pharmacological revascularization consists of fibrinolytic therapy with antiplatelet and anticoagulant therapy. In regard to the anticoagulant therapy, low molecular weight heparins (LMWHs) are of special importance. LMWHs cause less complications (bleeding, thrombocytopenia, better bioviability) in comparison with unfractionated heparin (UFH). Some studies on use of LMWHs in ACS, show that LMWHs are equally efficient and safe as UFH, causing less complications (different types of hemorrhagic complications) (ESSENCE, TIMI 11B (enoxaparin), FRAXIS-fraxiparin), whereas some studies show better efficacy and safety of enoxaparin in therapy of acute ST-elevated myocardial infarction (ASSENT 3, ASSENT 3 PLUS, HART II, AMI-SK). MATERIAL AND METHODS: INCLUSION CRITERIA: acute anterior myocardial infarction with ST-elevation, first myocardial infarction, no other structural heart defects, no signs of cardiogenic shock. Our study included 30 patients receiving fibrinolytic therapy with streptokinase, antiplatelet therapy and LMWH during 6 days, and 30 patients receiving UFH instead of LMWH. The follow-up period lasted for 6 months. RESULTS: Significantly more patients receiving unfractionated heparin presented with major adverse cardiac events (73.3%) in regard to patients in the study group (44.2% nadroparin, 39.8% enoxaparin) (p = 0.025). In the group receiving UFH, 6.7% patients had hemorrhagic complications, while none of patients receiving LMWHs. An equal number of patients died. CONCLUSION: Patients who were treated with LMWHs experienced less major adverse cardiac events and lower mortality. None suffered from hemorrhagic complications. PMID- 17345827 TI - [Effects of interferons on hepatitis C virus infection]. AB - INTRODUCTION: The consequences of hepatitis C virus infections (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma) are one of the major problems in clinical medicine. The persistence of infection in spite of high specific antibody titre suggests that the virus has the abillity to "escape" the immunological response. INTERFERON THERAPY: Interferons are important components of the early host response to infection. They have antiviral, antiproliferative, and immunomodulatory activities. Many viruses have developed the ability to "annul" or alleviate the action of interferon by preventing its synthesis or by interfering with signaling pathways in the cells. During acute infection some of the non-structural proteins of HCV block regulatory factors that are responsible for the synthesis of endogenous infection. Within a cell, interferon induces a number of genes to produce proteins that prevent virus replication. Among them, the most important are RNA-dependent protein kinase and the eukaryotic initiation factor. However, viral proteins, especially viral envelope proteins and nonstructural protein 5A, prevent their phosphorylation and activation which enhance virus replication. These are the facts that have to be considered when using IFN in chronic hepatitis C patients. PMID- 17345828 TI - [A gastrointestinal stromal tumor--case report]. AB - INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. They frequently occur in the stomach and small intestine, but they rarely occur in the colon and rectum. CASE REPORT: This is a case report of a patient with a GIST involving the cecum, and acute obstruction of the small intestine. A 47-year-old male patient was admitted to the emergency surgery department with abdominal pain and distension lasting for a few days. Clinical examination revealed tenderness in the right iliac fossa. Routine hematologic testing revealed anemia, and abdominal x-ray multiple air-fluid levels in the small intestine. Based on the clinical findings, we decided to perform an explorative laparotomy. A large cecal tumor was detected. The proximal parts of the small intestine were severely distended. DISCUSSION AND CONCLUSION: GISTs are more common in the stomach (60-70%) and the small intestine (25-35%), than in the colon, rectum and esophagus. The most frequent complications associated with GISTs are obstructions and hemorrhages. Surgical resection is the primary treatment of GISTs. Radiotherapy and chemotherapy are generally ineffective. Continuous postoperative follow-up is necessary, because most recurrences occur within the first 2 years after complete surgical resection. In the past few years, surgical resection was followed by adjuvant tyrosine kinase inhibitor therapy. PMID- 17345829 TI - [Myopericarditis during acute Epstein-Barr virus infection: a case report]. AB - INTRODUCTION: Complications associated with infectious mononucleosis are rare, but occasionally they can occur involving hematological, neurological, cardiological and pulmological complications, as well as liver and spleen disorders, sometimes with lethal outcome. The most important cardiac complications are myocarditis and pericarditis. CASE REPORT: An 18-year-old male patient was admitted to the Departement of Infectious Diseasees with clinical picture of infectious mononucelosis, while symptoms appeared 7 days before admission. He was under observation and treatment for nineteen days when clinical, radiographic and echocardiographic findings revealed development of myopericarditis and he was transferred to the Cardiology Department. He was treated with non-steroidal antiinflammatory drugs, beta-blockers, antibiotics and other symptomatic therapy. He became afebrile 35 days after admission, and was discharged on the 50th day in good condition. DISCUSSION: Myocarditis may develop as a complication of an infectious disease, and is usually caused by a direct viral infection, as well as, toxic and autoimmune mechanisms. Myocarditis attributed to Epstein-Barr virus infection is probably caused by autoimmune mechanisms: autoantibodies activate the complement or cause cellular cytotoxicity. CONCLUSION: Myopericarditis is not a common complication of acute Epstein-Barr virus infection. Transvenous endomyocardial biopsy is an established method required for exact diagnosis. In this case it was not done, due to some technical reasons. Thus, there is a high probalitiy that this patient had myopericarditis. PMID- 17345830 TI - [Microbiological diagnosis of tuberculosis in Serbia in the period 2001-2003]. AB - INTRODUCTION: The National tuberculosis Reference Laboratory (NTRL) and the National TB Laboratory Network in Serbia, provided data on drug susceptibility profiles of M. tuberculosis, incidence of TB among laboratory workers and on protective measures. MATERIAL AND METHODS: The TB laboratory network in Serbia comprises 46 laboratories. 11 laboratories perform acid fast microscopy only, 24 perform microscopic and culture examinations, and complete identification and drug susceptibility testing (DST) is performed in 11 laboratories. Protective measures for laboratory workers are mostly inadequate. Four cases of occupational TB were reported over the study period. RESULTS: DST was performed in 61.8% to 62.8% of bacteriologically proven TB cases. Isolates of M. tuberculosis strains showing drug-resistance ranged from 7.9% to 8.9%, while multidrug resistant (MDR) isolates varied from 2.2% to 2.5%. In order to determine the accuracy of DST in 6 local laboratories, NTRL carried out a quality assurance program for DST. Four laboratories reached 100% agreement with NTRL for rifampicin. At least 90% agreement with NTRL for isoniazid was achieved in three tested laboratories. CONCLUSION: A relatively low and stable rates of drug-resistant and MDR TB in our study indicate that the situation in Serbia is still satisfactory. However, a reliable surveillance of drug-resistant TB in the region requires routine DST of all patients with culture confirmed TB. This is one of the goals included in the new National TB Program. In summary, all laboratories in Serbia should be included in the quality assurance program and their number should be reduced in accordance with the annual number of analyses performed, geographical location and results of proficiency testing. PMID- 17345831 TI - [Haemorrhagic fever with renal syndrome (HFRS)--Hantavirus infection disease appearing in Poland]. AB - Authors take up the problem of occurrence of the haemorrhagic fever with renal syndrome in Poland and present the measures undertaken by Chief Sanitary Inspectorate, which brought to detection of the first, serologically confirmed case of HFRS in May 2005. They strongly emphasize the existence of the disease on Polish territory despite the poor epidemiological recognition, an possibility of its testing. PMID- 17345832 TI - [Estimation of clinical reliability and diagnostic usefulness of human fatty acid binding protein in acute coronary syndromes]. AB - Human fatty acid-binding protein (h-FABP) is an early marker of myocardial ischemia. It has high sensitivity and specificity comparing with conventional biomarkers such as troponin or creatine kinase. MATERIAL AND METHODS: The examinated group consisted of 83 patients, 31 (37,3%) women and 52 (62,7%) men. Every patient with chest pain typical for acute coronary syndrome was diagnosed from May until September 2005 in the emergency room of the Clinic of Cardiology. Every blood sample was tested for h-FABP with Cardio Detect med. test. RESULTS: Sensitivity for h-FABP at STEMI patients was: during first 3h - 95, 83%, 3-6h - 100%, 6-12h - 100%, over 12h - 100%. Sensitivity for h-FABP at NSTEMI patients was: 100%, 100%, 83% and 71,4%. CONCLUSIONS: H-FABP is an early diagnostic marker. Its sensitivity and specificity during first 6h from the beginning of chest pain comparing to troponin T and CK-MB is very high. Fast results given by measurements of h-FABP allow to make an early decision about further invasive treatment of patients. PMID- 17345833 TI - [Etiological factors of vascular grafts infections and their resistance to antibiotics]. AB - THE AIM: of our study was the identification of microorganisms causing vascular graft infections and the evaluation of their antimicrobial susceptibility. MATERIAL AND METHODS: 25 patients with infected vascular graft, took part in our research. In 19 patients late type of infection was recognized, in 6 the infection was qualified as early. Purulent discharge obtained from the fistula was inoculated on the bacteriological media. Antimicrobial susceptibility was assessed by disc-diffusion method. RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa proved to be the most frequently isolated microorganisms. Mixed infection, caused by two distinct bacteria, occurred in 5 patients; in all cases one species belonged to Gram-positive, and the second one to Gram-negative bacteria. In 50% of patients with early type infection different species of Gram negative rods were present, in 37,5% of them S. aureus and S. epidermidis were isolated. In late type infection Gram-negative rods were isolated from 54,5% of patients and Gram-positive bacteria from 31,5% of patients. The most frequently isolated species appeared to be Pseudomonas aeruginosa. The isolated species of bacteria varied depending on the degree of infection (according to Shilagy and Samson). CONCLUSIONS: A diversity of isolated species, the presence of mixed infections and resistance patterns typical for hospital flora among bacteria infecting vascular grafts cause that antibiotic therapy should always be based on the results of microbiological examination. PMID- 17345834 TI - [Hemostatic markers of endothelial injury in ischaemic stroke caused by large or small vessel disease]. AB - THE AIM: of the study was to compare hemostatic markers of endothelial injury in patients with ischaemic stroke caused by large vessel disease (LVD) or small vessel disease (SVD). MATERIAL AND METHODS: We studied 30 patients with LVD and 41 patients with SVD (recruited out of 585 patients with ischaemic stroke) as well as 30 control subjects. Etiology of ischaemic stroke was established according to the TOAST criteria. In patients being 3-12 months after stroke we registered age, sex and the presence of common risk factors for stroke. We measured serum concentration of fibrinogen and plasminogen activator inhibitor 1 (PAI-1), activity of von Willebrand factor (vWF) and the level of beta thromboglobulin (beta-TG). RESULTS: The concentration of fibrinogen was greater in patients with LVD (3.56 +/-0.88 g/L) when compared to patients with SVD (2.78 +/-0.69 g/L, psmallest): levocetirizine > cetirizine > fexofenadine 180mg = fexofenadine 120mg > loratadine = desloratadine. CONCLUSIONS: Following the end of the treatment, the effect of the antihistamines on skin reaction was subsiding in such an order: after 24 hours in case of loratadine and desloratadine, after two days for both doses of fexofenadine, and 3-4 days for cetirizine and levocetirizine. PMID- 17345840 TI - [Concentrations of soluble forms of adhesive particles: sVCAM-1, sPECAM-1, sVAP in early localized and late disseminated borreliosis]. AB - OBJECTIVE: Serum concentration of sVCAM-1, sPECAM- i sVAP in Lyme borreliosis patients with early localized-erythema migrans (EM) and disseminated Lyme arthritis (LA), before and after treatment were estimated. MATERIAL AND METHODS: Twenty subjects with EM, and 20 persons with LA were enrolled to examinations. Control group consisted of 10 healthy blood donors. Concentrations of sVCAM-1, sPECAM- and sVAP were performed with ELISA kits (Bender Med. System) Statistic analysis were performer with ANSTAT i Statistica PI, programs as well ROC curves. RESULTS: In group of early localized Lyme borreliosis essentially increase of serum concentrations of sVCAM and sPECAM were stated, in late, disseminated (LA), essentially increase of sVAP concentration was stated. CONCLUSION: Measurement of serum concentrations of soluble forms some adhesion molecules In liquid compartments can be a potential marker of disease activity, and differentiation among Early localized and late disseminated stages of Lyme borreliosis. PMID- 17345841 TI - [The plasma levels and diagnostic utility of granulocyte colony stimulating factor (G-CSF) and macrophage - colony stimulating factor (M-CSF) in ovarian cancer patients]. AB - G-CSF and M-CSF are of the glycoproteins called colony-stimulating factors (CSFs). Some clinical investigations have shown an autologous production of G-CSF and M-CSF in various human cell lines in vitro and by tumors in vivo. AIM OF STUDY: We have investigated the plasma levels and diagnostic utility of G-CSF M CSF and commonly accepted tumor marker, such as CA 125 in ovarian cancer patients before surgery and healthy subjects. MATERIAL AND METHODS: We tested 30 patients with ovarian cancer and 30 healthy women (control group). G-CSF and M-CSF were determined using enzyme-linked immunosorbent assay (ELISA), CA 125 was measured by microparticle enzyme immunoassay (MEIA). RESULTS: G-CSF, M-CSF and CA 125 plasma levels were significantly higher in ovarian cancer patients compared to the control group. The diagnostic sensitivity of M-CSF was higher than for G-CSF and CA 125 (57%, 50% i 53%, respectively). The diagnostic specificity was high and equal for all tested parameters (93%). Positive predictive value was higher for M-CSF and CA 125 (equal 89%). Negative predictive value was the highest for M CSF in comparison to G-C.SF and CA 125 (68%, 65%, 66,7%, respectively). CONCLUSIONS: Our study suggests that especially M-CSF can be clinically useful in diagnostic ovarian cancer, but further investigation and confirmation by a prospective study is necessary. PMID- 17345842 TI - [Prospective study on incidence of primary hyperparathyroidism in patients with goiter]. AB - Primary hyperparathyroidismus (PHPT) may coexist with goitre. Measurement of calcium concentration in blood serum is recommended before goiter operation. However, because of subclinical PHPT with normocalcemia this screening is insufficient for diagnosis of all PHPT cases. THE AIM: of the study is prospective evaluation of PHPT incidence in patients operated because of goitre. MATERIAL AND METHODS: The study was performed in group of 158 patients (145 women, 13 men) operated because of non-toxic goitre --115 patients--(SNN) and toxic--43 patients--(SNT). Calcium concentration (Ca), phosphorus concentration (P) and alkaline phosphatase activity (ALP) have been measured in all patients a day before operation. When this parameters has been out of normal range, parathormone concentration (PTH) was measured. PHPT was diagnosed, when PTH has been higher then normal range. Following Ca, P, ALP and PTH measurement was performed 3 months after operation to confirm or exclude the diagnosis of PHPT RESULTS: Values of Ca, P and ALP was out of normal range in 47 (37 with SNN and 10 with SNT) of 158 patients (29,7%). Higher PTH concentration (average 101,5 pg/ml) was in 16 of 47 patients (10, 1% of 158 patients). There was no hypercalcemia in any patient with PHPT PHPT was diagnosed in 12 (10,4%) patients with SNN and 4 (9,3%) with SNT. 12 patients were applied to following screening 3 months after operation. Among this patients value of Ca, P and ALP out of normal range was ascertained in 8 patients (66,7%). In 4 patients was higher PTH concentration. Increased PTH concentration and CA, P ALP concentration in normal range was observed in 1 patient three months after operation. In 5 of 12 (41,7%) patients was confirmed remaining PHPT although operation (average PTH 87,1 pg/ml). CONCLUSIONS: Primary hyperparathyroidismus coexist with similar incidence in patients with SNN and SNT Standard PHPT screening is proper because of PHPT incidence in up to 10% thyroid operated patients. PMID- 17345843 TI - [A case of haemorrhagic fever with renal syndrome (HFRS)]. AB - In our article we describe clinical and epidemiological analysis of the first case of haemorrhagic fever with renal syndrome (HFRS)--with serological confirmation--in Poland. PMID- 17345844 TI - [Tuberculosis ulcerosa of the anus and anal fissure accompanied by pulmonary tuberculosis]. AB - Dermal tuberculosis is being rarely diagnosed and its incidence in Poland is less than I % of all registered cases of this disease. A case of the alcohol abusing patient with diagnosed tuberculosis ulcerosa of the anal fissure and pulmonary tuberculosis has been described. Bacteriological confirmation has been achieved using PCR and Bactec 460 methods. Complete healing of the cutaneous lesions and regression of radiological titers in lungs has been achieved as a result of applied typical antituberculotic treatment. Delayed diagnostics of the patient (6 months from occurrence of the cutaneous lesions) endangered other persons, including healthcare employees' health to infection with tubercle bacillus. This speaks for a need of continuous reminding physicians that infection with tuberculosis may manifest itself from various organs. PMID- 17345845 TI - [Overlap syndrome autoimmune hepatitis and primary biliary cirrhosis associated with antiphospholipid syndrome]. AB - The paper presents diagnostic problems and therapeutic management in a case of 34 year old woman with antiphospholipid syndrome (APS) connected with overlap syndrome: autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). Life threatening cardiac arrhythmia was the first clinical manifestation of the disease. Pulmonary embolism occurred a few months later, with the presence of antiphospholipid antibodies. The diagnosis of AlH and PBC was made as a result of further research of complex immunological disturbances observed in the patient and after liver biopsy. PMID- 17345846 TI - [The chosen aspects of hospital infections]. AB - The paper presents some basic data on hospital infections and their influence in evaluation of hospital functioning. The most common infections, microorganism which are the cause of them, the role of patient immunological state, ways of spreading infections and ways of preventing them have been presented. PMID- 17345847 TI - [The role of tumor necrosis factor and interleukin-6 in polycystic ovary syndrome]. AB - Polycystic ovary syndrome (PCOS), which was described for the first time 70 years ago, is a frequent endocrinopathy. It is assessed that PCOS occurs in 6-10% women at reproductive age. However, the pathogenesis of this syndrome is still not clear. Recently it was observed that it is possible that proinflammatory cytokines participate in the development of PCO syndrome. Therefore the aim of present study is to review the current literature on a role of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) in the pathogenesis of polycystic ovary syndrome. TNF-alpa and IL-6 are recognized mediators of insulin resistance, which is the best examined link in the pathogenesis of PCO syndrome, these cytokines can also directly increase the activity of hypothalamic - pituitary - ovarian axis and hypothalamic - pituitary - adrenal axis. CONCLUSIONS: 1. Tumor necrosis factor-alpha and interleukin-6 participate in the pathogenesis of PCO syndrome through very complex mechanisms, but further study are necessary to explain them more precisely. 2. It seems that described cytokines may be the links that connect obesity and the development of PCO syndrome. PMID- 17345848 TI - [Prolactin receptors in the prostate]. AB - Following article describes available information presenting current knowledge on prolactin receptors expression and prolactin actions in the prostate gland. Prostate is strongly androgen dependent gland, however poseses receptors for other ligands including hypophyseal hormones and growth factors. More over prolactin is also locally produced and secreted acting also in paracrine way on the prostate. Prolactin alone and in cooperation with these hormones and growth factors plays essential role in regulation morphology and function of prostate gland, takes part in embryonic development, secretory function and pathological stages in prostate. Studies carried out in the human and animals in vivo and in vitro revealed presence of prolactin receptors in normal, benign and malignant prostate tissues. PMID- 17345849 TI - [Diabetic complications within ocular surface]. AB - Authors present one of the ocular diabetic complications--diabetic keratoepitheliopathy. The aim of this article is to summarize the knowledge about diabetic keratoepitheliopathy, its causes, manifestations and treatment options. Diabetes mellitus is associated with structural and functional disturbances in eyelids, conjunctiva and cornea. There are also changes in tear film present. Diabetic neuropathy resulting from the biochemical poor control of diabetes is the probable basic cause of the pathology. Mechanisms responsible for these changes are still not well understood. The corneal and conjunctival complications may occur spontaneously. But more often they arise from undue stress of intraocular surgery procedures. The incidence of diabetic keratoepitheliopathy in diabetic patients is high. However, it is rarely diagnosed. Effectiveness of symptomatic treatment with use of common medications is not satisfactory and it needs further investigation. PMID- 17345850 TI - [Spondylarthrosis etiopathogenesis]. AB - Spinal pain syndrome is a fast growing "pandemic" disease in highly civilised communities. Dealing with the etiopathogenesis of its most popular cause- spondylarthrosis--requires the knowledge of anatomy and physiology of the spine, and the explanation of biomechanic phenomena occurring in it. Many theories explaining the progress of spondylarthrosis are based on the assumption that the primary reason for pathology is degeneration of intervertebral discs, caused mainly by forced changes of spatial geometry of the spine; namely prolonged sitting or carrying weights in a bent position. The work presents Kapandji's hypothesis, attractive, among others, for its simplicity; explaining pathological mechanisms occurring within intervertebral disc. The hypothesis has also been advanced that the initiator of the process are degenerative changes in intervertebral joints, resulting from the so - called muscle dysbalance. They may occur earlier and only secondarily lead to disorders within the disc. The dynamics of progress of the disease varies, and the progression of pathological disorders is connected with the above - mentioned improper motor activity; first of all with the cumulation of effects of microtraumas, resulting from excessive sitting and bending, which may considerably accelerate this process, especially in patients genetically predisposed. In the work the progress of pathological process was presented from the stage of primary changes in nucleus pulposus to the phase of advanced adaptive--compensatory productive reactions in developed spondylosis. PMID- 17345851 TI - An Unlikely Vision. Defying scientific dogma, blind kids in India are learning to see. PMID- 17345852 TI - [Transformation of steroids by actinobacteria: a review]. AB - Development of pharmaceutical industry is currently aimed at introducing biotechnological processes on a large-scale and thereby replacing multiple-stage chemical syntheses. Actinobacteria are efficient biocatalysts of many processes involving steroid bioconversion, which hold considerable importance for the synthesis of hormonal drugs. The potential to catalyze the conversion of a broad spectrum of steroid substrates makes it possible to expect efficient utilization of these microorganisms in development of new technologies of manufacturing steroid pharmaceutical substances. The review is a first attempt to systematize data on the potential of actinobacteria to catalyze diverse reactions of steroid transformation (such as hydroxylation, introduction and reduction of double bonds, oxidation of steroid alcohols, reduction of ketones, side chain de esterification and degradation, etc.), with emphasis on processes of practical biotechnological importance and progress in steroid bioconversion over the last ten years. PMID- 17345853 TI - [Oxygen can be replaced by artificial electron acceptors in reactions catalyzed by alcohol oxidase]. AB - For the first time, spectrometric and electrochemical studies demonstrated the possibility of using artificial electron acceptors in reactions catalyzed by alcohol oxidase. We report kinetic parameters of homogenous catalytic oxidation of formaldehyde by organic redox compounds belonging to different structural classes (toluidine blue, methylene blue, 2,6-dichlorophenolindo-phenol, and p benzoquinone) and replacing dioxygen in these reactions. p-Benzoquinone, having the highest redox potential, proved to be the most efficient artificial electron acceptor of all compounds studied. PMID- 17345854 TI - [Regulation of phenol oxidase activity with sulfur dioxide as the base for production of high-quality instant green tea]. AB - The possibility to regulate phenoloxidase activity with sulfur dioxide was studied. It was found that this compound is a potent inhibitor of phenoloxidase of the reversible and mixed type. The inhibitory effect of sulfur dioxide on phenoloxidase provided grounds for a new biotechnological approach to the production of instant green tea. This approach allows increasing the yield of the extractive and the proportion of phenolics in the extractive, thereby improving the organoleptic quality of the product. PMID- 17345855 TI - [Oxidation of luminol with peroxidase from royal palm leaves]. AB - We optimized the conditions for luminol oxidation by hydrogen peroxide in the presence of peroxidase (EC 1.11.1.7) from royal palm leaves (Roystonea regia). The pH range (8.3-8.6) corresponding to maximum chemiluminescence was similar for palm tree peroxidase and horseradish peroxidase. Variations in the concentration of the Tris buffer were accompanied by changes in chemiluminescence. Note that maximum chemiluminescence was observed in the 30 mM solution. The detection limit of the enzyme assay during luminol oxidation by hydrogen peroxide was 1 pM. The specific feature of palm tree peroxidase was the generation of a long-term chemiluminescent signal. In combination with the data on the high stability of palm tree peroxidase, our results indicate that this enzyme is promising for its use in analytical studies. PMID- 17345856 TI - Simultaneous co-immobilization of glucose oxidase and catalase in their substrates. AB - Glucose oxidase (GOD) and catalase (CAT) were simultaneously co-immobilized onto magnesium silicate (florisil) by covalent coupling. Glucose was added in immobilization mixture and hydrogen peroxide which is the substrate of CAT was produced in coupling mixture during immobilization time. Therefore, co immobilization of GOD and CAT was carried out in presence of both their substrate: glucose and hydrogen peroxide, respectively. The effect of glucose concentration in immobilization mixture on activities of GOD and CAT of co immobilized samples were investigated. Maximum GOD and CAT activities were determined for samples co-immobilized in presence of 15 and 20 mM glucose, respectively. Co-immobilization of GOD and CAT in presence of their substrates highly improved the activity and reusability of both enzymes. PMID- 17345857 TI - [Transglycosylation of L-ascorbic acid]. AB - Cyclodextrin glucanotransferases (CGTase, EC 2.4.1.19) produced by mesophilic, thermophilic, and halophilic bacilli, as well as maltase (EC 3.2.1.20) produced by various strains of Saccharomyces cerevisiae have been applied for transglycosylation of L-ascorbic acid using starch, maltodextrin, gamma cyclodextrin, and maltose as donors of glucosyl residue. The CGTases produced by thermophilic strains are the most efficient. The degree of transglucosylation is more than 60%. PMID- 17345858 TI - [The effect of liposomes on the growth and sensitivity of Mycobacterium smegmatis to isoniazide]. AB - The effects of the liposome form of isoniazide (IN) and liposomes without IN on the growth of Mycobacterium smegmatis were studied. Fluorescent assay demonstrated that the fraction of liposomes that interacted with M. smegmatis amounted to 1-3%. It was shown that the IN efficiency in a liposomal form decreased depending on the liposome composition and concentration as compared with the IN in water solution. A preincubation of mycobacteria with liposomes led to a decrease in their sensitivity to IN. An analogous effect was observed when incubating M. smegmatis with oleic acid. It was postulated that the relative resistance of M. smegmatis to the antibiotic when using lipids as a carbon substrate appeared due to a change in the agent's metabolism and should be taken into account when testing in vitro the liposomal forms of antibiotics. PMID- 17345859 TI - [Adaptation of aerobic methylobacteria to dichloromethane degradation]. AB - A shortening of the lag phase in dichloromethane (DCM) consumption was observed in the methylobacteria Methylopila helvetica DM6 and Albibacter methylovorans DM10 after prior growth on methanol with the presence of 1.5% NaCI. Neither heat nor acid stress accelerated methylobacterium adaptation to DCM consumption. Sodium azide (1 mM) and potassium cyanide (1 mM) inhibited consumption of DCM by these degraders but not by transconjugants Methylobacterium extorquens AM1, expressing DCM dehalogenase but unable to grow on DCM. This indicates that the degrader strains possess energy-dependent systems of transport of DCM or chloride anions produced during DCM dehalogenation. Inducible proteins were found in the membrane fraction of A. methylovorans DM10 cells adapted to DCM and elevated NaCl concentration. PMID- 17345860 TI - [Features of the toxic action of 2,4,6-trinitrotoluene on Escherichia coli K12]. AB - 2,4,6-Trinitrotoluene present in a culture of Escherichia coli K12, at a concentration of 200 mg/l, caused a decrease in the total cell population and the population of colony-forming units, increased permeability of the external lipoprotein envelope, and increased the refractive index of cells. The shape of some cells changed from rod-like to coccoid, and cell size decreased. The specific rate of glucose consumption and the content of NADH (NADPH) in cells decreased. The changes of these morphological and physiological features were reversible, tending to normalize after reduction of 2,4,6-trinitrotoluene concentration in the course of cultivation. PMID- 17345861 TI - Temperature cycling to improve the ethanol production with solid state simultaneous saccharification and fermentation. AB - Simultaneous saccharification and fermentation (SSF) widely used in submerged state could be effective in solid state. Solid state SSF was first compared with solid state separate hydrolysis and fermentation on ethanol production. Ethanol yield using solid state separate hydrolysis and fermentation (SHF) in 5 days was only half of that in solid state SSF in 3 days. In solid state SSF, the ethanol concentration using temperature cycling (10 h at 37 degrees C followed by 15 min at 42 degrees C) was 2 times that using constant 37 degrees C within 72 h, reached 5.2%. PMID- 17345862 TI - [A comparative characterization of fungal melanin and the humin-like substances synthesized by Cerrena maxima 0275]. AB - Comparative studies of fungal melanin and two preparations of the high-molecular weight humin-like substances formed during a solid-phase cultivation of the basidiomycete Cerrena maxima 0275 for 45 and 70 days were performed. The fungal melanin from Aspergillus niger and the humin-like substances synthesized by the basidiomycete C. maxima 0275 are similar in their physicochemical properties (elemental composition and behavior in acids and alkalis) and auxin-like activities. However, these biopolymers differ, essentially, at the structural level. According to IR spectroscopy data, the obtained humin-like substances display a higher similarity to natural humic acids and are more diverse in their functional groups compared with fungal melanins. Presumably, this is connected with the fact that laccase is involved in formation of humin-like substances; moreover, this enzyme is involved not only in the synthesis of these polymers, but also in their modification and degradation. PMID- 17345863 TI - [The correlation between the synthesis of beta-carotene and zygote formation by Blakeslea trispora heterothallic strains]. AB - It was demonstrated for the first time that the level of carotenogenesis by the heterothallic Blakeslea trispora strains intensively forming zygospores decreased under conditions of a surface cocultivation during their sexual interaction as compared with the strains grown separately. On the contrary, carotenogenesis was stimulated during a sexual interaction of the strains incapable of forming zygotes. In a submerged culture, the zygote-forming pairs of strains synthesized a considerably larger amount of trisporic acids but a smaller amount of carotenoids than the strains not forming zygospores. The discovered inverse dependence between zygote formation and carotenogenesis allowed us to suggest the inability to form zygotes as a criterion for selecting carotenogenic strain pairs. PMID- 17345864 TI - [Galactosylated derivatives of low-molecular-weight chitosan: production and properties]. AB - Chitosan, a binary heteropolysaccharide consisting of 2-acetamide-2-deoxy-beta-D glucopyranose and 2-amino-2-deoxy-beta-D-glucopyranose residues linked in different proportions via beta-glycosidic bonds. The presence of a primary amino group in the chitosan structure allows for the synthesis of various derivatives. The procedure of obtaining activated N-hydroxysuccinimide esters with the use of lactobionic acid was applied to obtain galactosylated derivatives of low molecular-weight chitosan with a substitution degree varying from 8 to 23%. The properties of these derivatives (viscosity, solubility, and biodegradability) were studied. These derivatives are well soluble at pH values greater than the acidity constant of amino groups of chitosan (6.5). Broadening the pH range towards increase and the presence of galactose residues allows these derivatives to be used in working with biological objects. PMID- 17345865 TI - [A highly branched storage polyglucan in the thermoacidophilic red microalga Galdieria maxima cells]. AB - The thermoacidophilic red alga Galdieria maxima is capable of heterotrophic growth. The content of carbohydrates in H. maxima grown heterotrophically increases by a factor of 4, reaching as much as 60% of cell dry weight. The increase in the level of carbohydrates in cells is due to accumulation of a storage alpha-glycan. According to a specific cleavage to glucose catalyzed by amyloglucosidase and the high positive specific optical rotation characteristic of polyglucans, this polysaccharide can be classified as a floridean starch. The data of 1H NMR spectroscopy and the results of methylation showed that the average length of the unbranched regions of the polysaccharide molecule is six to seven glucose residues. The degree of branching of the starch molecule of G. maxima is greater than that of storage polysaccharides of other red algae, glycogens of yeast, and phytoglycogens of cyanobacteria. PMID- 17345866 TI - [Polysaccharides of cell cultures of Silene vulgaris]. AB - Callus and suspension cultures of campion (Silene vulgaris) produced pectin polysaccharides, similar in structure to the polysaccharides of intact plants. The major components of the pectins were D-galacturonic acid, galactose, arabinose, and rhamnose residues. The maximum content of pectins was found in callus. The monosaccharide composition of arabinogalactans isolated from cells and a culture medium of callus cultures were similar, with the ratio between arabinose and galactose of 1: (2.3-6.5) being retained. The arabinogalactans from the cells and culture medium of the suspension cultures also had a similar structure, and the arabinose to galactose ratio was 1: (1.5-1.8). In contrast to the callus cultures, the suspension cultures produced arabinogalactans with an increased content of arabinose residues and a decreased content of galactose residues. The greatest content of arabinogalactan was detected in the culture medium of the suspension cultures. PMID- 17345867 TI - [The effect of intercultivar substitution of wheat Triticum aestivum L. chromosomes on lipoxygenase activity and its correlation with the technological properties of flour]. AB - The effects of intercultivar substitution of individual chromosome pairs (except for 1B, 6D, and 7A) in the wheat cultivars Saratovskaya 29 and Janetzkis Probat, differing in quality, on specific lipoxygenase activity, the grain yield per spike, and the main technological properties of flour and dough were studied. It was demonstrated that the substitution of individual chromosomes of the recipient cultivar Saratovskaya 29 with the homologous chromosomes of the donor cultivar Janetzkis Probat caused significant changes in lipoxygenase activity and several other quality characteristics. The correlations between the lipoxygenase activity and the parameters of physical dough properties were determined. Three molecular forms of lipoxygenase (Lpx-1, Lpx-2, and Lpx-3), differing in the value of surface charge and enzymatic activity, were detected by native PAGE. PMID- 17345868 TI - [Use of monoclonal antibodies against horse immunoglobulin in an enzyme immunoassay of bacterial toxins and anatoxins]. AB - Immunization of BALB/c mice by horse antiserum against diphtheria made it possible to obtain IgG1 monoclonal antibodies (MoAbs) 2B7E4 specific for light chains of horse immunoglobulin (Ig). Unlike commercial preparations of anti-horse immunoglobulin antibodies, which are specific for the whole Ig molecule or its Fc fragment, the peroxidase (HRP) conjugate of the MoAb, 2B7E4-HRP did not interact with human, mouse, rabbit, and sheep Igs, or horse albumin. The conjugate obtained was used with MoAbs against bacterial toxins and commercial horse anatoxins, as a universal reagent in sandwich enzyme immunoassay (ELISA) for bacterial toxins and anatoxins. The detection sensitivity of diphtheria toxin/anatoxin equaled 0.0005 Lf/ml; tetanus toxin and anatoxin were detected with sensitivities of 20 LD50/ml and 0.005 UI/ml, respectively. A similar sandwich ELISA for botulinum anatoxins (group measurement) allowed types A, B, and E to be detected at 0.02, 0.002, and 0.001 UI/ml, respectively; selective measurement was only possible in the case of type E anatoxin (0.001 UI/ml). PMID- 17345869 TI - [Oral administration of protein solutions]. AB - Experiments on animals showed that native proteins may diffuse into the blood flow after oral administration of diluted protein solutions. An in vitro study led us to hypothesize that treatment with diluted solutions is accompanied by a decrease in the rate of protein proteolysis and accelerated protein diffusion through the intestinal mucosa. PMID- 17345870 TI - [An improved method of photometric determination of cyclodextrin glucanotransferase activity]. AB - The method of spectrophotometric determination of cyclodextrin glucanotransferase (CGTase, EC 2.4.1.19) activity with the use of phenolphthalein as a colored reagent has been improved. This technique includes an enzymatic reaction at 40 degrees C for 60 min in 2% starch, with subsequent supplementation of the reaction mixture (0.5 ml) with the phenolphthalein reagent (3.0 ml) prepared in 0.1 M potassium carbonate buffer (pH 11.0) according to a special procedure, and measurement of the optical density of the obtained mixture at 553 nm. The activity was calculated using the exponential growth equation that connects a drop in the optical density and the degree of dilution of the enzyme. The described technique is suitable for working in a sufficiently broad range of specific activity of beta-CGTase and does not require precise adjustment of the degree of dilution of solutions analyzed. PMID- 17345871 TI - The communicative functions of touch in humans, nonhuman primates, and rats: a review and synthesis of the empirical research. AB - Although touch is one of the most neglected modalities of communication, several lines of research bear on the important communicative functions served by the modality. The authors highlighted the importance of touch by reviewing and synthesizing the literatures pertaining to the communicative functions served by touch among humans, nonhuman primates, and rats. In humans, the authors focused on the role that touch plays in emotional communication, attachment, bonding, compliance, power, intimacy, hedonics, and liking. In nonhuman primates, the authors examined the relations among touch and status, stress, reconciliation, sexual relations, and attachment. In rats, the authors focused on the role that touch plays in emotion, learning and memory, novelty seeking, stress, and attachment. The authors also highlighted the potential phylogenetic and ontogenetic continuities and discussed suggestions for future research. PMID- 17345872 TI - [Mechanisms of regulation of the food intake: recent advances]. AB - The mechanisms deputed to energetic control have been selected by ancestral diets resulting from the nutrient disposal during the evolution. Discovery of the leptin and its downstream peptidergic pathways has increased our understanding of the physiological system that regulate food intake in the last decade. Hypothalamus plays a key role in the regulation of the peripheral and central signals of energy requirements. Insulin and leptin, that reflect the adipose status, are able to long term influence these circuits. Gut hormones acutely modulated the pathways, resulting in a stimulation effects by ghreline, or in a inhibition effects by PYY and oxintomoduline. Moreover, brain centres signal energy homeostasis by monoamine release and endocannabinoid system. This review discusses the network of neuronal and hormonal signals, which contribute to the energetic control. PMID- 17345873 TI - [Post-partum hemorrhage: new therapeutic options]. AB - Bleeding remains a major cause of morbidity and mortality in obstetrics. Recombinant activated factor VII (rFVIIa), which was originally developed for the treatment of bleeding in hemophilic patients with inhibitors, has been recently employed to prevent or control bleeding in several other non-hemophilic bleeding conditions. Among the newer, "off-label" clinical applications of rFVIIa, its use in the treatment of obstetrical bleeding unresponsive to conventional therapy has generated intense interest. The existing literature on the use of rFVIIa in post partum hemorrhage (PPH) is analysed in this review. Although supported by few and uncontrolled studies, on the whole the published data suggest a potential role of rFVIIa in the management of PPH. However, further evidences are needed in order to better assess the optimal dose, the effectiveness and the safety of rFVI-Ia in such critical bleeding conditions. PMID- 17345874 TI - [Cost analysis of tumor-induced osteolysis treated with intravenous zoledronic acid and pamidronate: a time-motion study]. AB - A time-motion study was performed by evaluating time and use of medical supply resources in the administration of zoledronic acid and pamidronate as palliative care of tumor-induced osteolysis within the clinical setting of three Italian oncology day-hospital sites. The direct medical costs were similar for both treatments (Euro 226 for zoledronic acid versus Euro 231 for pamidronate). With the exclusion of the pharmacological therapy, most of the difference in costs derives from nurses' labor costs, which is related to the longer infusion time for pamidronate (1 h, 47 min versus 28 min for zoledronic acid). PMID- 17345875 TI - [Secondary amyloidosis complicated rheumatoid arthritis, prevalence study in Italian population]. AB - Amyloidosis refers to the extracellular deposition of proteinaceous insoluble fibrils in various tissues, resulting in organ compromise. The most common form of amyloidosis occurs secondary to chronic inflammatory disease, in which AA fibrils, derived from the acute phase protein, serum amyloid-A (SAA). We evaluated the prevalence of AA with lip biopsy on 106 rheumatoid arthritis patients (according to 1988 ARA criteria), asymptomaticwith regard to amyloidosis (90 females, 16 males). On histological salivary gland samples we evaluated the presence of AA by an immunohistochemical method [Anti Human Amiloid clone MC-1 (DAKO, Italy)]. We observed a positivity of AA on 8/106 patients (5 F/3 M) 7.54%. When the total data were divided into three groups considering the different lenght of the disease (number of years) we observed the following prevalence data: group A, years of disease < 3, 2/45, 4.44% (F 1/M 1), group B, years of disease 3-5, 2/26, 7.69% (F 1/M 1), group C, years of disease > 5, 4/35, 11.42%. The statistical analysis showed a significative difference between group A and B (p < 0.025), between group B and C (p < 0.025) and between group A and C (p < 0.01). The 8 patients with AA positivity showed also an high disease activity in comparison with 98 negative patients: DAS 5.62 +/- 0.48 vs 4.36 +/- 0.79, DAS28 5.84 +/- 0.76 vs 4.48 +/- 0.87 (p < 0.05). Our data showed that secondary AA amyloidosis prevalence in asymptomatic Italian rheumatoid arthritis patients was 7.54%; moreover this complication was present in 4.44% of early rheumatoid arthritis patients. PMID- 17345876 TI - [Dermatomyositis and hypokalemia: a difficult diagnosis]. AB - The idiopathic inflammatory myopathies are systemic autoimmune diseases characterizes by chronic muscle inflammation. The frequent extramuscolar manifestations contribute to the morbidity and mortality of the disease. The goal of medical therapy is based on immune suppression with first-line agent glucocorticoids and additional immunosuppressants can be used when severe side effects occur or glucocorticoids are considered to be ineffective. We report the case of a female patient with dermatomyositis and reduced potassium levels. This case illustrates the difficulty of establishing the differential diagnosis of hypokalemia. PMID- 17345877 TI - [Hepatocellular carcinoma: tumoral or peritumoral disease?]. AB - Hepatocellular carcinoma (HCC) is a highly malignant cancer with prognosis and survival still poor mainly because of HCC reoccurrence and cancer metastasis. No drugs are so far available to reduce or block HCC progression, likely because the molecular mechanisms involved in cancer proliferation and spread are mainly unknown. In this review, we will discuss the role of the tissue microenvironment in affecting HCC clinical outcome. Therefore, based on new pathogenetic findings, tissue microenvironment will be considered as potential target for new therapeutic approaches. The aim of this review is to stimulate the debate on the translational research in the HCC field. PMID- 17345878 TI - [Antidepressant drugs and breastfeeding]. AB - The post-partum period, as well as pregnancy, is associated with an increased risk of anxiety and/or affective disorders. Postnatal depression, frequently in co-morbidity with anxiety symptoms, is recognised as the most frequent form of maternal morbidity after delivery, with a prevalence rate estimated between 5% to 15%. Among antidepressant drugs, the SSRIs are considered the drugs of choice in the treatment of post-partum affective disorders, particularly in the major depression. It is, thus, crucial from a clinical standpoint to establish, in the newborn whose mother needs to be treated with an SSRI, the safety profile of these drugs during breastfeeding. The benefits of breastfeeding, on the other hand, both for the nursing mother and the infant, are in fact very well documented. Unfortunately, all antidepressant drugs, including SSRIs, cross into breast milk and the milk-to-plasma ratio, a measure proposed to establish the amount of drug transferred to maternal milk, does not seem to be a reliable parameter to predict the safety of these drugs. From the available literature, however, it seems that among SSRIs, paroxetina and sertralina offer the best safety profile, as these drugs has never been associated with unsafe reports in suckling infants. Despite these reassuring but preliminary data, more studies are needed to better assess the safety of the antidepressant drugs in the infants exposed during breastfeeding. As general rule, it is important to recommend if the mother wishes to breastfeed her infant while taking an antidepressant, that the baby should be closely monitored in order to detect, as soon as possible, any unwanted drug-related side effect. PMID- 17345879 TI - [Depression in old age: a diagnostic and therapeutic challenge]. AB - In old age, depression mainly affects those with chronic medical illness, severe disability or mental decline. Depression in elderly worsens the outcomes of many medical illness and increases mortality. Age-related processes, including arteriosclerosis, inflammatory and degenerative diseases, may compromise the integrity of prefrontostriatal pathways and amygdala leading to increased vulnerability to depression. Environmental factors, such as impoverishment, isolation, relocation, caregiving and bereavement, contribute to further increase susceptibility to depression or triggering depression in already vulnerable elderly people. Suitable treatment of depression in elderly reduces the symptoms, prevents suicidal ideation, improves cognitive and functional status and helps patients to develop the skills needed to cope with their disability or psychosocial adversity. Prevention of depression in given pathological conditions may greatly improve the outcomes, mostly the recovery of function and quality of life, as well as the mortality risk. Therefore, it should be considered the opportunity of a depression prophylaxis, particularly in those circumstances in which the risk of depression is noteworthy increased, such as stroke, cancer, institutionalization, etc. PMID- 17345880 TI - Reflections on the cot death cases. AB - Sally Clark, Angela Cannings and Trupti Patel not only suffered the tragic sudden deaths of two or more babies. They were then accused, and in the first two cases convicted, of their murder. The misuse of statistics at Sally Clark's trial had profound consequences, especially for her, but also for the subsequent cases. Ray Hill reflects on the statistical issues involved. PMID- 17345881 TI - Misleading statistics within criminal trials. AB - Richard Nobles and David Schiff revisit the Sally Clark case and consider the presentation by nonstatisticians of statistical evidence in court. PMID- 17345882 TI - Statistics on trial. AB - Although the concerns of Statistics and the Law might seem to have little to do with one other, they do share some fundamental common interests, such as interpretation of evidence, hypothesis testing and decision-making under uncertainty. Philip Dawid takes up questions that, though long of interest to a few scholars, have only recently become the focus of much attention. PMID- 17345883 TI - Appealing statistics. AB - In the case of Regina v. Adams [1996], DNA evidence seemed to suggest that there was a 1 in 200 million chance that an innocent person would match the DNA found at the crime scene. Peter Donnelly explains how he subsequently became involved in the case and found himself trying to explain Bayes' theorem to judge and jury. (See p.18 for an explanation). PMID- 17345884 TI - Bayes' theorem, and its role in the law. PMID- 17345885 TI - Patient perceptions of medium secure care. AB - Research into patients' experience of medium secure psychiatric services is in its infancy despite growing interest in user involvement in mental health care as a whole. The work reported here aimed to provide an opportunity for patients to reflect upon their understanding of their route into secure psychiatric provision and their time spent in one large unit in the West Midlands. Most (65%) of the patients taking part were admitted to medium security through the criminal justice system. The average length of stay was 18 months (range, two months to two years six months). The experience of being admitted to secure care was generally described as frightening though many patients expressed relief that they were now receiving help. Half of those interviewed thought they had no choice about treatment. Nevertheless, eight said they trusted their doctors to make the right decision about medication. Generally patients thought their relationships with multi-disciplinary team members were positive and felt able to approach them with any concerns. Overall, patients who participated in this study were optimistic about their experience of medium secure care. They felt the advantages of hospital care compensated for the disadvantages, particularly as their mental state stabilised and they gained insight into their illness. Areas of concern for patients were lack of privacy and uncertainty about how long they were likely to remain in hospital. PMID- 17345886 TI - Healthcare law in France: towards healthcare emancipation for minors. AB - In France, since 1974 the rights of minors have been gaining ground. The first provisions to this end concerned medical acts in relation to the minor's sexuality (contraceptives and pregnancy termination). The law dated March 4, 2002, relating to patients' rights, gave more scope to this movement, by widening minors' rights so that they could demand confidentiality with regard to their parents. The minor's exercising of these rights can pose a lot of problems. In French law, parental authority is the main representation of the minor. The medical doctor treating a minor must obtain parental authorization. However, the public healthcare code provides that the doctor can override parental wishes during some situations (emergency; parents refuse). But these situations are exceptional. Since 2002, the legislator has gone further, by allowing the doctor to grant requests for care by the minor without parental authorization. However, parental authority remains the normal framework for the protection of a minor. The doctor will have to judge the reasoning and motives of a minor requesting confidentiality regarding their parents in order to decide whether he should grant or refuse care in such conditions. PMID- 17345887 TI - Gender identity disorder and its medico-legal considerations. AB - The general belief among behavioural scientists and physicians is that gender identity disorder or transsexualism is an identifiable and incapacitating disease which can be diagnosed and successfully treated by reassignment surgery in carefully selected patients. Although many advances have been made in the reassignment surgery techniques, phalloplasty still remains a major challenge; to date, no ideal technique has been developed. The new gender created by the reassignment surgery has, in turn, led to many legal complications for post operative transsexuals because, in many developed and the developing countries, transsexuals are not given a legal identity, thereby adding to their agonies and miseries. This article examines the historical perspective, genesis and management of gender identity disorder, or transsexualism, and draws attention to the medico-legal considerations. PMID- 17345888 TI - Widening the scope of the hybrid order. AB - Hybrid orders under section 45A of the Mental Health Act allow for convicted mentally disordered offenders to be given a sentence of imprisonment and simultaneously transferred to hospital for psychiatric treatment. In England and Wales their use is limited to patients with psychopathic disorder and the order has been little used. Two recent judgments by the House of Lords and the Court of Appeal have interpreted the law in a manner which widens its scope, allowing treatment of a greater range of offenders under the order, including offenders with co-morbid mental illness. PMID- 17345889 TI - Medical liabilities of the French physician passenger during a commercial air flight. AB - Nearly two billion passengers travel each year on commercial air flights. More elderly people and/or people with a pre-existing condition are taking to the air and with the anticipated growth of air travel, in-flight illnesses and injuries are expected to increase as well. Even if in-flight medical events and deaths are still uncommon, physician passengers are occasionally called upon to render assistance. Although no case law exists as yet in France, physicians who often travel on commercial flights should be aware of the risks they run if they do not respond to the well-known call, 'Is there a doctor on board?', or if they assist a sick passenger. This paper describes in-flight resources available to a physician who is called upon to treat an ill or injured passenger. Two questions concerning the French physician passenger are discussed: What are the liabilities of the physician who does not respond to the call of a medical event aboard an aircraft? What are the liabilities of the physician providing assistance to a sick passenger? The different liabilities and also the legal status of the French physician passenger are examined. PMID- 17345890 TI - A post-mortem study of the upper gastro-intestinal tract in head injury cases. AB - A post-mortem study was conducted to find the incidence, morphological changes and distribution of lesions in the upper gastro-intestinal tract (GIT) in victims of head injury who had survived for 24 hours or longer. The study involved naked eye and microscopic examination of the mucosa of the upper gastro-intestinal tract. In this study all the victims of head injury who had survived one or more days showed definite evidence of damage to the lining of the stomach wall. The severity of the damage increased with survival time. The damage observed was in the form of congestion, mucosal haemorrhage, superficial erosions, and superficial ulcerations accompanied by frank haemorrhage. PMID- 17345891 TI - Elderly suicide rates in the United Kingdom: trends from 1979 to 2002. AB - The proportion of elderly in the population is increasing due to a falling birth rate and increased life expectancy, and suicide rates increase with age. Trends in elderly suicide rates over a 24-year period, 1979 to 2002, were examined. Differences in suicide rates between elderly men and women and between the age bands 65 to 74 years and 75+ years were examined. Data was ascertained from the WHO website. Suicide rates for men and women for the age-bands 65 to 74 years and 75+ years declined over the 24-year study period. Suicide rates were higher in men than women for both the age bands. In men, suicide rates were higher in the 75+ age-band than in the 65 to 74 years age-band. Various national initiatives may have contributed to the decline in suicide rates. The challenge will be to sustain the decline, given that the population is ageing and suicide rates generally increase with age. PMID- 17345892 TI - Claims made by children in Japan for injuries caused before birth. AB - In Japan, under Article 721 of the Civil Law 1896, a child who is born disabled is able to file a claim against the person who injured him or her in the mother's womb. On the other hand, there are no legal rights for a stillborn child who died in the mother's womb as it is traditionally considered that a foetus is not a person. Consequently, the parents of a stillborn child are not able to recover damages as administrators for the wrongful death of their child. They are only able to recover damages for pain and suffering related to the stillbirth of their child. This study compares the legal status of a disabled live-birth child and a stillborn child in Japan with those in a similar situation in the U.K. and U.S.A. PMID- 17345893 TI - Trends in fatal motor vehicle accidents in Transkei region of South Africa. AB - This paper aims to estimate the incidence of motor vehicle accident (MVA) related deaths and identify the factors associated with the causes of the high road death toll in Transkei region. A retrospective review and analysis was performed of all medico-legal autopsies (n=6181) between January 1993 and December 1999, of which 39% (1778/4525) were deaths as a result of MVAs. During the seven-year period (January 1993-December 1999), MVA deaths in Transkei region accounted for an average of 63 deaths per 100,000 population per year. It reached a peak of 80 deaths per 100,000 in 1997, and then slowly came down to 48 deaths per 100,000 in 1999. MVA deaths have come down from 39% (248) of all trauma-related deaths in 1993 to 29% (193) in 1999. The male/female ratio is 3.3:1; and 50% of victims were between 21 and 40 years of age. In conclusion, there are high motor vehicle accident-related deaths in Transkei region of South Africa. PMID- 17345894 TI - Autopsy study of fatal deliberate self harm. AB - A retrospective autopsy study of fatal deliberate self harm (FDSH) was undertaken in the mortuary of Kasturba Hospital, Manipal, Southern India over a period of 12 years (1993-2004). Out of 1917 cases autopsied, 21.2% were deaths due to deliberate self harm (DSH). The male sex (66.1%) and victims in the third decade of life (35.9%) predominated. More than two-thirds of the decedents were married. More fatalities were observed during the winter season (35.8%) and in the day time (62.2%). Dispair with life (61.9%) was the most common motive for FDSH. The majority of fatalities were due to poisoning (73.5%), where organophosphorous compounds topped the list (71.9%). About one-third of the victims survived for 18 to 24 hours after DSH. PMID- 17345895 TI - Post-anaesthetic maternal death in a patient with mediastinal large B-cell lymphoma: a case report. AB - A 32-year-old female underwent laparoscopic salpingectomy of an ectopic (third) pregnancy under general anaesthesia, at approximately six weeks' amenorrhoea. She developed severe respiratory distress after extubation and died on the second postoperative day. It appears that she had a history of a mild, persistent productive cough for a period of about a month prior to the operation that was attributed to an upper respiratory tract infection. Autopsy demonstrated the presence of a large mediastinal tumour, whose existence was apparently unsuspected preoperatively, encasing the ascending thoracic aorta, aortic arch and the proximal segments of the brachiocephalic and subclavian arteries, and causing extrinsic airway compression. Subsequent microscopic examination showed histological and immunohistochemical features of a mediastinal large B-cell lymphoma. It is thought that the mechanical effects exerted by the advanced mediastinal tumour upon the airways and the thoracic cage, coupled with the pathophysiological effects of general anaesthesia on respiratory movement and airway patency, had led to the patient's unfortunate demise in early pregnancy. PMID- 17345896 TI - Sudden death during worker transportation due to massive pulmonary thromboembolism: a case report. AB - This is a report on a 30-year-old black man who suddenly died in the worker transportation vehicle in which he had been quietly sitting for thirty minutes. No information about his medical or surgical history or any family history has been obtained. This case is intended to highlight the fact that forensic autopsy is a valuable tool to recognize the cause of death and that fatal pulmonary thromboembolism still remains a post-mortem diagnosis. In this case report, the autopsy found a fresh saddle pulmonary thromboembolus associated with partially organized thrombi of the inferior vena cava. Can a prolonged seated position encourage thrombus formation? We think that seat-related factors and especially patient-related factors intervene together in the development of thromboembolic events. In our medico-legal unit, having no means to search for these factors, we speculated on the various causes that could be involved in the occurrence of venous thromboembolism in our subject. We emphasize the importance of focusing research on genetic factors and the impact of traditional medicine in African people. PMID- 17345897 TI - Skeleton used for anatomical study brought for medico-legal autopsy: a case report. AB - Knowledge of human anatomy is essential for all those practising medicine. The human skeleton is invariably used to study the anatomy of body structures. For this, many human skeletons are obtained from the market by students and teachers and are kept at home or in hostel rooms. However, after use the skeleton has to be disposed off properly. In the present case, a human skeleton used for study purposes was thrown away in garbage and someone informed the police about presence of skeletal remains in the garbage. The case was registered by the police and the skeletal remains were brought for medico-legal autopsy. PMID- 17345899 TI - Assisted dying for the terminally ill. PMID- 17345900 TI - Action over nurses' pay. PMID- 17345901 TI - Courage under fire. PMID- 17345902 TI - When might is right. AB - As bodyguard to the Dalai Lama and European royalty, Zeb Glover knows all about self-defence and martial arts--skills he is keen to share with nurses. PMID- 17345903 TI - It's all in the timing. AB - Specialist nurses are helping to promote the Parkinson's Disease Society's Get it on Time campaign to ensure patients do not suffer delays in the administration of their crucial drugs. PMID- 17345904 TI - A financial hangover. AB - As the Christmas and new year credit card bills thud through the letterbox, the extent of your overspending can become all too obvious. But there are sources of help. PMID- 17345905 TI - Forgotten specialty. PMID- 17345906 TI - Responding appropriately to patients with chronic illnesses. AB - A significant proportion of the population lives with chronic illness and nurses are likely to come into contact with these patients on a regular basis. However, health professionals do not always recognise or respond supportively to such patients. This article explores some of the negative responses that occur and suggests more appropriate ways to work with this group of patients. PMID- 17345907 TI - The importance of adequate fluid and fibre intake during pregnancy. AB - Dietary advice about fluid and fibre for pregnant women is limited in comparison to information on folic acid. Low intakes of these nutrients can affect the health status of pregnant women. Research indicates that pregnant women consume fibre at lower levels than the recommended intake for the non-pregnant population (Anderson 1986, Derbyshire et al 2006). Low fluid intake has been linked to constipation in pregnancy, particularly in the third trimester. This article provides information for health professionals about how much fibre and fluid should be consumed during pregnancy. PMID- 17345908 TI - Menorrhagia: causes, diagnosis and treatment options. AB - This article examines the causes of menorrhagia and outlines approaches to diagnosis and treatment. It includes a description of the normal menstrual cycle and the clotting cascade. The research findings suggest that inherited bleeding disorders account for many cases of menorrhagia. PMID- 17345909 TI - Cardiovascular system. PMID- 17345910 TI - Care of patients with fungating malignant wounds. AB - Any nurse who has cared for a patient with a fungating malignant wound will know that this is a challenging aspect of the care provided to patients with advanced cancer. This article examines the aetiology of fungating wounds and three core principles of fungating wound management and patient care. This is an under researched area of clinical care and the literature that guides malignant wound care is drawn from disciplines such as oncology, chronic wound care and palliative care. PMID- 17345911 TI - Effective wound management: identifying criteria for infection. AB - This article provides an overview of the European Wound Management Association's (2005) position document Identifying Criteria for Wound Infection and outlines its relevance and clinical applicability. The document is divided into four parts: understanding wound infection; clinical identification of wound infection- a Delphi approach; identifying criteria for pressure ulcer infection; and identifying surgical site infection in wounds healing by primary intention. Each part is discussed separately. PMID- 17345912 TI - Freedom to learn. PMID- 17345913 TI - Nurses need the law. PMID- 17345914 TI - Alcohol abuse as a rite of passage: the effect of beliefs about alcohol and the college experience on undergraduates' drinking behaviors. AB - Qualitative studies of alcohol's ritual influences indicate that college undergraduates who drink heavily tend to view alcohol use as integral to the student role and feel entitled to drink irresponsibly. Our analyses, based on a standardized measure of these beliefs administered to approximately 300 students, confirmed these findings. Among our sample, beliefs about alcohol and the college experience had an effect on levels of alcohol consumption similar in magnitude to that of other variables commonly associated with a risk for heavy drinking. Moreover, the alcohol beliefs index moderated the effects of three risk factors- gender, high school drinking, and friends' use of alcohol--on respondents' drinking behaviors. These findings are discussed within the context of the anthropological literature on liminality and rites of passage and with regard to strategies for intervention that address the structural roots of the widespread abuse of alcohol on college campuses. PMID- 17345915 TI - Cigarette smoking, friendship factors, and social norm perceptions among central and Eastern European high school students. AB - Studies investigating smoking behavior among adolescents living in post communistic Central-European countries are sparse. This study focused on the relationship between cigarette smoking, certain friendship factors, and social norm perceptions among 1,886 Central-Eastern European adolescents from high schools in Hungary, Slovakia, Czech Republic, and Romania. Smoking behavior was related to having friends who smoke, ease or difficulty making new friends, time spent with friends after school and during evenings, and estimations of the prevalence of smoking by schoolmates. Because these youth appear to overestimate the prevalence of smoking by schoolmates, the use of a norms-correction strategy may have potential merit in smoking prevention efforts targeting these adolescents. Smoking prevention and reduction are critical issues for Central Eastern European youth because they appear to smoke cigarettes at a high rate. PMID- 17345916 TI - A randomized trial of motivational interviewing and feedback with heavy drinking college students. AB - Motivational interviewing (MI) is a brief intervention that has been shown to reduce heavy drinking among college students. Because all college studies of MI to date have included a personalized feedback report, it remains unclear which of the components is necessary to produce behavior change. This study evaluated the separate and collective effects of MI and feedback among 122 "binge" drinking college students. Participants were randomized to: (1) MI with feedback, (2) MI without feedback, (3) Mailed feedback only, (4) MI with mailed feedback, or (5) Assessment only control. At an eight-week follow-up, all groups reduced their consumption, peak BAC, consequences, and dependence symptoms. For females, there were reductions in consequences and dependence symptoms in groups that received feedback, as compared to groups that did not receive feedback. For females, there was an effect of the feedback on consequences and dependence symptoms, but was no overall effect of MI on any outcome measure. PMID- 17345917 TI - Authoritative parenting and sensation seeking as predictors of adolescent cigarette and marijuana use. AB - Adolescents with high sensation-seeking tendencies often seek out thrill seeking experiences to satisfy their need for stimulation and sensation. In many cases, sensation-seeking adolescents fulfill their need for stimulation and sensation by using illicit substances. However, not all high sensation seekers use drugs, although the factors that prevent or buffer sensation seeking remain unexplored. This study fills this gap in extant research by examining the role of authoritative parenting as a protective factor that prevents or buffers cigarette and marijuana use by adolescents with high sensation-seeking tendencies. Data from 1461 adolescents attending 6th through 8th grades in central Colorado were gathered during a semester-long classroom-based intervention to prevent the onset or further use of cigarettes. Results indicate that authoritative parenting moderated the effect of sensation seeking on adolescent marijuana attitudes, intentions, and peer influence but not behaviors. Further, authoritative parenting was a stronger influence than sensation seeking on cigarette-related outcomes with just the opposite effect observed for marijuana-related outcomes. PMID- 17345918 TI - An evolutionary psychology perspective on sex differences in exercise behaviors and motivations. AB - Researchers have found that men and women pursue sex-appropriate strategies to attract mates. On the basis of intrasexual competition, men should be more likely to enact behaviors to look larger, whereas women should be more likely to enact behaviors to look smaller. The types of exercises that each performs should reflect this expectation. The present study replicates and extends work by L. Mealey (1997) on sex differences in exercise behavior. In the present study, male participants focused their energy on gaining muscle mass and enhancing their upper body definition, whereas female participants focused their energy on losing weight with emphasis on their lower body. Both sexes reported efforts to improve their abdominal region. It appears that men and women adopt sex-appropriate exercise behavior as a method of self-enhancement for intrasexual competition. PMID- 17345919 TI - Male physical attractiveness in Britain and Greece: a cross-cultural study. AB - The waist-to-chest ratio (WCR), body mass index (BMI), and waist-to-hip ratio (WHR) are the major cues to women's ratings of men's bodily attractiveness (J. T. Fan, W. Dai, F. Liu, & J. Wu, 2005; D. M. Maisey, E. L. E. Vale, P. L. Cornelissen, & M. J. Tovee, 1999; V. Swami & M. J. Tovee, 2005b). The authors examined the relative importance of each of these cues cross-culturally in Greece and Britain. Participants were 36 British and 40 Greek women who rated a set of images of real men with known WCR, BMI, and WHR. The results showed that, regardless of the cultural setting, WCR was the primary determinant of men's physical attractiveness to women, with BMI playing a minor role. However, there were also cross-cultural differences: The Greek women showed a stronger preference for a lower WCR and smaller overall body weight than did the British women. The authors considered possible explanations of these findings. PMID- 17345920 TI - Does substance use affect reliabilities of the Implicit Association Test? AB - The authors examined whether use of alcohol or marijuana affected reliability of the Implicit Association Test (IAT; A. G. Greenwald, D. E. McGhee, & J. L. K. Schwartz, 1998). Consistent with research indicating the possibility that marijuana use depletes cognitive resources, the authors found worse reliabilities for participants who recently used marijuana than for those who had not. Recent alcohol users and nonusers demonstrated similar IAT reliability. Subsequent analyses indicated that reliability differences between marijuana users and nonusers were most pronounced when participants began with incongruous tasks and then switched to congruous tasks. Results were consistent with work on the residual costs of task switching that indicates that effortful tasks promote interference with tasks that follow. The authors discussed results in terms of IAT scoring procedures and the prevalence of use of alcohol and marijuana on university campuses. PMID- 17345921 TI - The moderating role of ambivalent sexism: the influence of power status on perception of rape victim and rapist. AB - The authors examined the effect of ambivalent sexism on others' perceptions of alleged-rape incidents, in which there are socioeconomic status differences between the victims and their perpetrators. The dependent variables included measures of minimizing rape, blaming the victim, excusing the perpetrator, and determining the length of the recommended sentence. The results indicated 4 noteworthy findings: First, individuals who scored high on the hostile power relation (HPR) measure tended to minimize the seriousness of rape incidents. Second, the HPR measure moderated victim blame only in the powerful-man scenario. Third, participants who scored high on the HPR measure tended to believe that the alleged rapist held less responsibility. Fourth, female participants tended to give longer sentences. PMID- 17345922 TI - Pizza and pop and the student identity: the role of referent group norms in healthy and unhealthy eating. AB - Using the Theory of Planned Behavior (I. Ajzen, 1985, 1991) and referent group (student) norms and identification (D. J. Terry & M. A. Hogg, 1996), the authors longitudinally predicted healthy eating intentions and behavior in a sample of 137 university students. Specifically, attitudes, subjective norms, and perceived control predicted intentions at Time 1, which predicted self-reported behavior at Time 2. There was also a link between intentions and observed behavior at Time 2. Beyond the planned behavior variables, referent group norms for university students' eating behavior interacted with participants' identification as students to predict healthy eating intentions. The authors discussed implications for researcher's conceptualization of normative influence and for interventions into this group's eating behavior. PMID- 17345923 TI - Ethnic differences in endorsement of the Protestant work ethic: the role of ethnic identity and perceptions of social class. AB - The authors examined ethnic differences in endorsement of the Protestant work ethic (PWE; M. Weber, 1905) among Black (n = 96) and White (n = 149) college students and tested whether differences in ethnic identity and perceptions of social class mediated the relationship between ethnicity and the endorsement of PWE values. Blacks were higher in levels of ethnic identity, more likely to see themselves as working or middle class, and less likely to endorse the PWE. Only perceptions of social class partially mediated the relationship between ethnicity and PWE values. The authors concluded that perception of social class is an important construct that might influence the cultural psychology of different ethnic groups. The authors recommended further research involving PWE and other cultural variables. PMID- 17345924 TI - Need for closure, the Big Five, and public self-consciousness. PMID- 17345925 TI - Pathophysiology of gastro-oesophageal reflux disease. AB - Gastro-oesophageal reflux disease is a condition in which the reflux of gastric contents into the oesophagus provokes symptoms or complications and impairs quality of life. Typical symptoms of gastro-oesophageal reflux disease are heartburn and regurgitation but gastro-oesophageal reflux disease has also been related to extra-oesophageal manifestations, such as asthma, chronic cough and laryngitis. The pathogenesis of gastro-oesophageal reflux disease is multifactorial, involving transient lower oesophageal sphincter relaxations and other lower oesophageal sphincter pressure abnormalities. As a result, reflux of acid, bile, pepsin and pancreatic enzymes occurs, leading to oesophageal mucosal injury. Other factors contributing to the pathophysiology of gastro-oesophageal reflux disease include hiatal hernia, impaired oesophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. Hiatal hernia contributes to gastro-oesophageal reflux disease by promoting lower oesophageal sphincter dysfunction. Impaired oesophageal clearance is responsible for prolonged acid exposure of the mucosa. Delayed gastric emptying, resulting in gastric distension, can significantly increase the rate of transient lower oesophageal sphincter relaxations, contributing to postprandial gastro oesophageal reflux disease. The mucosal defensive factors play an important role against development of gastro-oesophageal reflux disease, by neutralizing the backdiffusion of hydrogen ion into the oesophageal tissue. While the pathogenesis of oesophageal symptoms is now well known, the mechanisms underlying extra oesophageal airway manifestations are still poorly understood. Two hypotheses have been proposed: direct contact of gastric acid with the upper airway and a vago-vagal reflex elicited by acidification of the distal oesophagus, leading to bronchospasm. In conclusion, gastro-oesophageal reflux disease can be considered as the result of a complex interplay of factors, all promoting the contact of gastric acidic contents with the oesophageal mucosa, leading to different degrees of oesophageal damage. PMID- 17345926 TI - Manifestations of gastro-pharyngo-laryngeal reflux disease. AB - In the last few years, gastro-oesophageal reflux disease has received renewed interest from the ENT specialists. The symptomatology can vary on account of the differences between the gastro-oesophageal reflux and the laryngo-pharyngeal reflux as far as concerns both symptomatology and clinical-pathogenic aspects. The symptoms and the clinical laryngoscopic aspects are discussed. PMID- 17345927 TI - ENT manifestations of gastro-oesophageal reflux in children. AB - Gastro-oesophageal reflux is common in children and is associated with morbidity rates that justify increasing interest in early diagnosis and appropriate medical or surgical treatment. In children ENT manifestations of gastro-oesophageal reflux mainly affect the larynx, ears, nose, paranasal sinuses and oral cavity. Main manifestations are laryngo-tracheal stenosis, laryngomalacia, otitis media with effusion, rhinosinusitis. PMID- 17345928 TI - Extra-laryngeal manifestations of gastro-oesophageal reflux. AB - Of the various otorhinolaryngological disorders for which it has been recognized that gastro-oesophageal reflux is a possible causal or associated aetiological factor, those manifestations localized in the rhino-sinus and auricular district are certainly the "least studied". Herein, therefore, these manifestations are described, focusing on the physio-pathological aspects and the more important pathogenic hypotheses of the cough, as well as other lung manifestations. PMID- 17345929 TI - Laryngeal carcinoma and laryngo-pharyngeal reflux disease. AB - A correlation between laryngo-pharyngeal reflux and laryngeal carcinoma is currently debated. Chronic inflammation is a mutagen factor confirmed in the cancerogenesis of various tumours. Aim of the present study was to evaluate, in an objective and consecutive way, with 24h multi-electrode pH-metry the presence of proximal and distal oesophageal reflux in patients presenting pre-cancerosis or squamous cell laryngeal and/or pharyngeal carcinomas. From our data, a strict correlation emerged between laryngo-pharyngeal reflux and neoplasias of the upper airways, documented through multi-electrode pH-metry. Data emerging from this study would seem to support the theory that the protracted exposure (> 20 years) to biliary reflux would represent a statistically significant added risk factor in the precancerous lesions and squamous pharyngo-laryngeal carcinoma as it occurs at oesophageal level. Moreover, a significant statistical association (p < 0.0001) emerged between laryngeal carcinoma and previous gastro-resection (odds ratio 3.8). PMID- 17345930 TI - Multicentric study: statistical correlation between clinical data and instrumental findings in laryngo-pharyngeal reflux: proposal for a new ENT classification of reflux. AB - Clinical pictures of laryngopharyngeal reflux, described in the literature, often differ considerably and are described with wide severity. Some classifications employ a total score i.e., addition of the assigned scores to single aspects of video-laryngoscopy. These classifications have the disadvantage of being complex, not reproducible and, in part, subjective. In this study, an original video laryngoscopic classification is proposed, based on a topographic criterion with distinction of anterior, from posterior and lateral, lesions and an anatomo pathological criterion that assigns a marked severity to the granulomatous and erosive lesions, in comparison with the erythematous and oedematous lesions. Four classes are proposed or grades of patients (A, B, C, D). The study was multicentric on 178 patients. Results were considered estimating the clinical parameters and the symptoms, correlating them at the stages of the classification proposed. The data obtained indicate that our classification presents an indicative distribution as far as concerns severity and it seems acceptable for efficacy and simplicity: no significant correlation emerged between the single manifestations and the severity of the objective picture; in the majority of cases, the most constant symptomatological triad was globus, cough and dysphonia. PMID- 17345931 TI - Management of gastro-oesophageal reflux disease: role of proton pump inhibitor test and upper gastro-intestinal endoscopy. AB - Authors report the available scientific evidence on the role of proton pump inhibitors and upper gastro-intestinal endoscopy in the management of patients with gastro-oesophageal reflux disease. Relative indications, advantages and pitfalls of various diagnostic and therapeutic strategies for cost-effective management of this condition are discussed. The most recent evidence-based guidelines are outlined. PMID- 17345932 TI - Medical treatment of gastro-oesophageal reflux disease. AB - The introduction, in the last two decades, of strongly effective acid suppressant drugs, such as proton pump inhibitors has radically modified the way of treating gastro-oesophageal reflux disease. In clinical trials, these agents have constantly been demonostrated to be more effective than other acid-suppressant agents such as H2-receptor antagonists in relief of symptoms and healing of oesophagitis, the two main goals of gastro-oesophageal reflux disease treatment. They provide a prompt clinical benefit to most patients and can be safely used in long-term gastro-oesophageal reflux disease management for maintenance of clinical and endoscopic remission, because of their negligible adverse-events profile. Therapeutic protocols vary depending on the severity of symptoms and the degree of oesophageal injury. In patients with mild symptoms and with minimal lesions at endoscopy, a "step-down" therapy, in the short-term, is considered the best medical strategy, while in the long-term the therapy "on-demand" appears to be a reasonable approach. Patients with non-erosive disease seem to have a lower response rate to proton pump inhibitor treatment. More severe grades of oesophagitis must be treated with full-dose proton pump inhibitors without withdrawal. Data on the treatment of extra-oesophageal manifestations of gastro oesophageal reflux disease are few and controversial. Overall, it appears that patients with extra-oesophageal symptoms of gastro-oesophageal reflux disease must be treated with higher doses of pharmacological treatment, principally with proton pump inhibitors, and with longer periods of treatment to achieve complete relief of symptoms, as compared with patients with typical symptoms of gastro oesophageal reflux disease and erosive oesophagitis. PMID- 17345933 TI - Endoscopic treatment of gastro-oesophageal reflux disease. AB - Gastro-oesophageal reflux disease is a common chronic disorder which has a severe effect on the patient's quality of life. In view of the high cost of medical therapy and the limitations of surgery, a variety of endoscopic techniques have been developed for the treatment of this condition, and these have shown apparently encouraging results, at least in the short- term. However, several inconsistencies have emerged between the efficacy of endoscopic treatment in improving symptoms and quality of life and a lack of improvement of objective parameters. Controlled studies are urgently needed in order to clarify the potential of endoscopic therapy. Currently, the use of endoscopic treatment should be limited to clinical trials. PMID- 17345934 TI - Laparoscopic Nissen-Rossetti fundoplication is effective to control gastro oesophageal and pharyngeal reflux detected using 24-hour oesophageal impedance and pH monitoring (MII-pH). AB - The study aims to evaluate, at medium- and long-term follow-up, the efficacy of Nissen-Rossetti fundoplication to control both gastro-oesophageal and pharyngeal reflux, detected with the use of 24-hour pH-multi-channel intra-luminal impedance. Of the 1000 patients who underwent Nissen-Rossetti fundoplication in our Division since 1972, the laparoscopic approach was adopted in 428 consecutive patients with gastro-oesophageal reflux disease. The study population consisted of patients from this group with one-year follow-up. Thirty-one patients had undergone pre-operative evaluation with pH-multi-channel intra-luminal impedance and were classified on the basis of clinical assessment into gastro-oesophageal, or pharyngeal reflux disease group. Pre-operative data are reported. Comparison between gastro-oesophageal reflux and pharyngeal reflux are extrapolated from pH multi-channel intra-luminal impedance. No conversion to open surgery and no mortality occurred. A major complication occurred in 4 patients (1.1%) and led to a re-intervention in 3. An excellent outcome was reported in 92.9% of the patients at mean follow-up of 83.2 +/- 7 months. Instrumental outcomes are discussed. In conclusion, Nissen-Rossetti fundoplication provides excellent protection from gastro-oesophgeal and pharyngeal reflux. The use of pH-multi channel intra-luminal impedance is suitable in patients candidate to anti-reflux surgery to detect non-acid reflux. PMID- 17345935 TI - Non-linear associations between laryngo-pharyngeal symptoms of gastro-oesophageal reflux disease: clues from artificial intelligence analysis. AB - The relationship between the different symptoms of gastro-oesophageal reflux disease remain markedly obscure due to the high underlying non-linearity and the lack of studies focusing on the problem. Aim of this study was to evaluate the hidden relationships between the triad of symptoms related to gastro-oesophageal reflux disease using advanced mathematical techniques, borrowed from the artificial intelligence field, in a cohort of patients with oesophagitis. A total of 388 patients (from 60 centres) with endoscopic evidence of oesophagitis were recruited. The severity of oesophagitis was scored by means of the Savary-Miller classification. PST algorithm was employed. This study shows that laryngo pharyngeal symptoms related to gastro-oesophageal reflux disease are correlated even if in a non-linear way. PMID- 17345936 TI - Laryngo-pharyngeal reflux: final remarks. PMID- 17345937 TI - Financial management: never a dull moment. PMID- 17345938 TI - Outsourcing transcription. PMID- 17345939 TI - Recent activity in managed-care litigation. What your practice needs to know to dispute insurer compliance. PMID- 17345940 TI - Managing costs. PMID- 17345941 TI - The urge to merge. Implementing a physician office EMR and integrating it with a hospital EHR. PMID- 17345942 TI - Payer negotiations. You have more power than you think. PMID- 17345943 TI - Double exposure. Higher deductibles, uninsured patients add to administrator's challenges. AB - The spread of high-deductible health plans and a rising number of medically uninsured patients could quickly unravel your practice's cash collection and accounts receivable performance. It could even undermine your reputation as a savvy manager of the practice's finances. To prevent that calamity, shift into preparation mode. Plan now to reduce collection delays and eliminate confusion as more patients move into consumer-directed health plans that combine high deductibles and out-of-pocket expenses with options such as health savings accounts that encourage patients to spend less, not more, for health care. PMID- 17345944 TI - Balancing act. Using the clinic scorecard to improve practice performance. AB - The balanced scorecard is a strategic management system that impels managers to focus on the performance metrics that drive success. It measures the business process and links a management method for process improvement to strategic goals. A medical practice can use a balanced scorecard to improve operational performance and quality or service, which generates higher levels of patient satisfaction and better financial management. PMID- 17345945 TI - Cause and effect. Understanding the production-profit relationship. AB - Regardless of administrative performance in managing reimbursement and overhead, income will fall below expectations if physician productivity fails to reach key thresholds. How do group practice administrators "manage" physician production levels when the owners can frequently undervalue the relationship between compensation levels and their own productivity? ANSWER: carefully and indirectly. PMID- 17345946 TI - Locks of love. PMID- 17345947 TI - James A. Dinsmoor (1921-2005): questions of science and life. PMID- 17345948 TI - Resurgence of integrated behavioral units. AB - Two experiments with rats examined the dynamics of well-learned response sequences when reinforcement contingencies were changed. Both experiments contained four phases, each of which reinforced a 2-response sequence of lever presses until responding was stable. The contingencies then were shifted to a new reinforced sequence until responding was again stable. Extinction-induced resurgence of previously reinforced, and then extinguished, heterogeneous response sequences was observed in all subjects in both experiments. These sequences were demonstrated to be integrated behavioral units, controlled by processes acting at the level of the entire sequence. Response-level processes were also simultaneously operative. Errors in sequence production were strongly influenced by the terminal, not the initial, response in the currently reinforced sequence, but not by the previously reinforced sequence. These studies demonstrate that sequence-level and response-level processes can operate simultaneously in integrated behavioral units. Resurgence and the development of integrated behavioral units may be dissociated; thus the observation of one does not necessarily imply the other. PMID- 17345949 TI - Timing, remembering, and discrimination. AB - Four pigeons were first trained in a timing procedure. In one condition, each trial began with the presentation of an X on the center key, followed by a delay (short or long), after which two side keys were lit. If the delay was short, pecks to the red side key were reinforced. If the delay was long, pecks to the green side key were reinforced. In a second condition, the opposite contingencies applied following presentation of a square on the center key. Choice responses were then tested at 10 time intervals ranging from short to long (1 to 4 s and 4 to 7 s in different conditions). The two timing conditions were combined to create a remembering condition in which correct responding depended upon discrimination of both the sample stimulus (X or square) and the delay interval (short or long). Choices varied systematically across delay in timing conditions, but in remembering conditions, accurate choice at the training delays did not initially generalize to intermediate delays. However, with prolonged training in the remembering task, the response pattern began to resemble that of the timing conditions. Generalization gradients were asymmetrical, in accordance with Weber's Law, in that greater generalization occurred with longer delays than with shorter delays. PMID- 17345950 TI - European starlings are capable of discriminating subtle size asymmetries in paired stimuli. AB - Small deviations from bilateral symmetry (fluctuating asymmetries) are cues to fitness differences in some animals. Therefore, researchers have considered whether animals use these small asymmetries as visual cues to determine appropriate behavioral responses (e.g., mate preferences). However, there have been few systematic studies of animals' abilities to visually discriminate such minor asymmetries. If the asymmetries cannot be discriminated, fluctuating asymmetry can not be a visual cue. Here, we report an investigation of European starlings' (Sturnus vulgaris) abilities to discriminate small size asymmetries. We trained starlings, through operant conditioning in a free-flight aviary, to discriminate achromatic, symmetric paired stimuli from size-matched asymmetric stimuli. By starting the learning process with a large asymmetry and progressing through sequential trials of decreasing asymmetry, we elucidated a behavioral limit to asymmetry discrimination. We found that starlings are capable of discriminating a 10% size asymmetry. There was weaker evidence for discrimination of 5% asymmetry but no evidence for signal discrimination at 2.5% size asymmetry. This level of asymmetry discrimination suggests that many size asymmetry cues in nature can be discriminated by birds. At each level of asymmetry discrimination, we also tested whether starlings could generalize their learned symmetry preference to unreinforced novel images. Consistent with previous findings, we found that starlings could generalize their symmetry preferences. PMID- 17345951 TI - Maternal nutrition and four-alternative choice. AB - Two groups of 10 male rats were trained to nose poke for food pellets at four alternatives that provided differing rates of pellet delivery on aperiodic schedules. After a fixed number of pellets had been delivered, 5, 10 or 20 in different conditions of the experiment, a 10-s blackout occurred, and the locations of the differing rates of pellet delivery were randomized for the next component. Two groups of rats were used: The AD group consisted of 10 rats born to dams that had normal (ad libitum) nutrition during pregnancy, whereas the 10 rats in the UN group were from dams exposed to reduced food availability during pregnancy. All pups received normal nutrition after birth. Choice between the nose-poke alternatives quickly adapted when the rates of pellet delivery were changed in both groups, but there were no consistent differences in the speed of adaptation between the two groups. The generalized matching relation failed to describe the allocation of responses among alternatives, but the contingency discriminability model provided a precise description of performance. PMID- 17345952 TI - Do infants show generalized imitation of gestures? AB - Two experiments were conducted to investigate generalized imitation of manual gestures in 1- to 2-year-old infants. In Experiment 1, 6 infants were first trained four baseline matching relations (e.g., when instructed "Do this", to raise their arms after they saw the experimenter do so). Next, four novel gestures that the infants did not match in probe trials were selected as target behaviors during generalized imitation Test 1; models of these gestures were presented on unreinforced matching trials interspersed with intermittently reinforced baseline matching trials. None of the infants matched the target behaviors. To ensure that these behaviors were in the infants' motor skills repertoires, the infants were next trained to produce them, at least once, under stimulus control that did not include an antecedent model of the target behavior. In repeat generalized imitation trials (Test 2), the infants again failed to match the target behaviors. Five infants (3 from Experiment 1) participated in Experiment 2, which was identical to Experiment 1 except that, following generalized imitation Test 1, the motor-skills training was implemented to a higher criterion (21 responses per target behavior), and in a multiple-baseline, across-target-behaviors procedure. In the final generalized imitation test, 1 infant matched one, and another infant matched two target behaviors; the remaining 17 target behaviors still were not matched. The results did not provide convincing evidence of generalized imitation, even though baseline matching was well maintained and the target behaviors were in the infants' motor skills repertoires, raising the question of what are the conditions that reliably give rise to generalized imitation. PMID- 17345953 TI - Conditional relations with compound abstract stimuli using a go/no-go procedure. AB - The aim of this study was to evaluate whether emergent conditional relations could be established with a go/no-go procedure using compound abstract stimuli. The procedure was conducted with 6 adult humans. During training, responses emitted in the presence of certain stimulus compounds (A1B1, A2B2, A3B3, B1C1, B2C2, and B3C3) were followed by reinforcing consequences (points); responses emitted in the presence of other compounds (A1B2, A1B3, A2B1, A2B3, A3B1, A3B2, B1C2, B1C3, B2C1, B2C3, B3C1 and B3C2) were not (i.e., extinction). During subsequent tests of emergent relations, new configurations (BA, CB, AC, and CA relations) were presented, formed by the recombination of training stimuli and structurally resembling tests usually employed in stimulus equivalence studies. Results showed that all 6 participants displayed immediate emergence of relations consistent with symmetry. Four participants exhibited emergent relations consistent with both transitivity and equivalence. These results indicate that a go/no-go procedure with compound stimuli can establish emergent conditional relations, thus providing a procedural alternative to the matching-to-sample procedures commonly used in studies of stimulus equivalence. PMID- 17345954 TI - The effects of differential training procedures on linked perceptual class formation. AB - When the stimuli in one perceptual class (A') become related to the stimuli in another perceptual class (B'), the two are functioning as a single linked perceptual class. A common linked perceptual class would be the sounds of a person's voice (class A') and the pictures of that person (class B'). Such classes are ubiquitous in real world settings. We describe the effects of a variety of training procedures on the formation of these classes. The results could account for the development of naturally occurring linked perceptual classes. Two perceptual classes (A' and B') were formed in Experiment 1. The endpoints of the A' class were called anchor (Aa) and boundary (Ab) stimuli. Likewise, the anchor and boundary stimuli in the B' class were represented as Ba and Bb. In Experiment 2, the A' and B' classes were linked by the establishment of one of four cross-class conditional discriminations: Aa-->Ba, Aa-->Bb, Ab- >Ba, or Ab-->Bb. Results were greatest after Aa-->Bb training, intermediate after Aa-->Ba and Ab-->Ba training, and lowest after Ab-->Bb training. Class formation was influenced by the interaction of the anchor/boundary values and the sample/comparison functions of the stimuli used in training. Experiment 3 determined whether class formation was influenced by different sets of two cross class conditional discriminations: Aa-->Ba and Ab-->Bb, or Aa-->Bb and Ab-->Ba. Both conditions produced equivalent results. Similarities were attributable to the use of anchor stimuli as samples and boundary stimuli as comparisons in each training condition. Finally, the results afterjoint Aa-->Ba and Ab-->Bb training were much greater than those produced by summing the results of Aa-->Ba training alone and Ab-->Bb training alone. This same synergy was not observed after joint Aa-->Bb and Ab-->Ba training or either alone. PMID- 17345955 TI - A model for residence time in concurrent variable interval performance. AB - A component-functions model of choice behavior is proposed for performance on interdependent concurrent variable-interval (VI) variable-interval schedules based on the product of two component functions, one that enhances behavior and one that reduces behavior. The model is the solution to the symmetrical pair of differential equations describing behavioral changes with respect to two categories of reinforcers: enhancing and reducing, or excitatory and inhibitory. The model describes residence time in interdependent concurrent VI VI schedules constructed from arithmetic and exponential distributions. The model describes the data reported by Alsop and Elliffe (1988) and Elliffe and Alsop (1996) with a variance accounted for of 87% compared to 64% accounted for by the Davison and Hunter (1976) model and 42% by Herrnstein's (1970) hyperbola. The model can explain matching, undermatching, and overmatching in the same subject under different procedures and has the potential to be extended to performance on concurrent schedules with more than two alternatives, multiple schedules, and single schedules. Thus, it can be considered as an alternative to Herrnstein's quantitative law of effect. PMID- 17345956 TI - Cui bono? A review of breaking the spell: religion as a natural phenomenon by Daniel C. Dennett. AB - The three requirements for a Darwinian evolutionary process are replication, variation and selection. Dennett (2006) discusses various theories of how these three processes, especially selection, may have operated in the evolution of religion. He believes that the origins of religion, like the origins of language and music, may be approached scientifically. He hopes that such investigations will open a dialog between science and religion leading to moderation of current religious extremism. One problem with Dennett's program, illustrating the difficulty of breaking away from creationist thinking, is Dennett's own failure to consider how Darwinian methods may be used to study evolution of behavioral patterns over the lifetime of individual organisms. PMID- 17345957 TI - A sensitive, reliable inexpensive touch detector. PMID- 17345958 TI - Influence of dietary fiber on inflammatory bowel disease and colon cancer: importance of fermentation pattern. AB - The benefits of dietary fiber on inflammatory bowel disease may be related to the fermentative production of butyrate in the colon, which appears to decrease the inflammatory response. The benefits of dietary fiber against colon cancer may be related to both fermentative and non-fermentative processes, although poorly fermentable fibers appear more influential. Dietary fiber fermentation profiles are important in determining optimal fibers for colonic health, and may be a function of structure, processing conditions, and other food components. A greater understanding of the relationships between fermentation rate and dietary fiber structure would allow for development of dietary fibers for optimum colonic health. PMID- 17345959 TI - Krill for human consumption: nutritional value and potential health benefits. AB - The marine crustacean krill (order Euphausiacea) has not been a traditional food in the human diet. Public acceptance of krill for human consumption will depend partly on its nutritive value. The aim of this article is to assess the nutritive value and potential health benefits of krill, an abundant food source with high nutritional value and a variety of compounds relevant to human health. Krill is a rich source of high-quality protein, with the advantage over other animal proteins of being low in fat and a rich source of omega-3 fatty acids. Antioxidant levels in krill are higher than in fish, suggesting benefits against oxidative damage. Finally, the waste generated by the processing of krill into edible products can be developed into value-added products. PMID- 17345960 TI - Supplemental calcium and risk reduction of hypertension, pregnancy-induced hypertension, and preeclampsia: an evidence-based review by the US Food and Drug Administration. AB - The labeling of health claims that meet the significant scientific agreement (SSA) standard (authorized health claims) and qualified health claims on conventional foods and dietary supplements requires premarket approval by the US Food and Drug Administration (FDA). FDA conducts an evidence-based review to determine whether there is sufficient evidence to support an authorized or qualified health claim. An evidence-based review was conducted on the human intervention and observational studies evaluating the role of supplemental calcium in reducing the risk of hypertension, pregnancy-induced hypertension, and preeclampsia. This review provides FDA's evaluation of the current scientific evidence on the role of supplemental calcium in reducing the risk of these three end points. Based on this evidence-based review, the agency concluded that the relationship between calcium and risk of hypertension is inconsistent and inconclusive, and the relationship between calcium and risk of pregnancy-induced hypertension and preeclampsia is highly unlikely. PMID- 17345961 TI - Dietary components impact histone modifications and cancer risk. AB - Epigenetics refers to the study of heritable changes in gene expression that occur without a change in the DNA sequence and constitute an important mechanism by which dietary components can selectively activate or inactivate gene expression. Alterations in histone acetylation and methylation are a common hallmark of human cancer. This review focuses on several histone-modifying enzymes that are associated with cancer development and their modification by bioactive food components. PMID- 17345962 TI - Molecular differentiation of congenital lactase deficiency from adult-type hypolactasia. AB - A limited fraction of the human adult population retains intestinal lactase phlorizin hydrolase (LPH) activity during adulthood, and this is called the lactase persistence phenotype. However, 95% of all adults have adult-type hypolactasia (ATH) and have difficulty digesting milk sugar. Rarely, some infants are born with an inability to digest lactase (congenital lactase deficiency or CLD) due to low levels of LPH activity, which results in severe clinical consequences if not properly diagnosed and treated by lactose avoidance. Recently, it has been shown that both recessive LPH deficiencies, CLD and ATH, are related to DNA variants affecting the lactase (LCT) gene, but they are mediated through very different molecular mechanisms. The LCT mutations resulting in childhood CLD lead to low LPH activity through nonsense-mediated LCT mRNA decay, whereas the critical nucleotide variants for the ATH phenotype represent distal enhancer polymorphisms, which regulate developmentally LCT transcript levels in intestinal cells. PMID- 17345963 TI - The myth of the gendered chromosome: sex selection and the social interest. PMID- 17345964 TI - Right problem, wrong solution: a pro-choice response to "expressivist" concerns about preimplantation genetic diagnosis. PMID- 17345965 TI - Compensation for gamete donation: the analogy with jury duty. PMID- 17345966 TI - The patient's work. PMID- 17345967 TI - Morality, prudential rationality, and cheating. PMID- 17345968 TI - Causation and intent: persistent conundrums in end-of-life care. PMID- 17345969 TI - Bioethics consultation and patient advocacy organizations: expanding the dialogue about professional conflicts of interest. PMID- 17345970 TI - Four paradigms of clinical research and research oversight. PMID- 17345971 TI - Montreal Statement on the Human Right to Essential Medicines. PMID- 17345972 TI - From patient to consumer in the medical marketplace. PMID- 17345973 TI - Tuberculosis in haemodialysis: a problem making a comeback. AB - Tuberculosis (TB) accounts for a significant proportion of all deaths by infectious diseases. Controlling tuberculosis is a major public health issue especially in the developing nations, where the rise of the disease's incidence varies between 5-30% and the rise reaches reduplication every 5-10 years. The consequences of the disease in renal dialysis patients vary between 3.7-6%, thus being 12-15 times higher than the rest of the population. PMID- 17345974 TI - Enhancing lifestyle through home haemodialysis. AB - The Sydney Dialysis Centre (SDC) supports 150 patients who dialyze in the home environment. Since its inception SDC has been assisting patients to modify their dialysis regime according to individual needs. In 2003-2004 a postal survey was sent to SDC patients who had changed their dialysis regime to ascertain the effect of this change on lifestyle. This article will present the results of the survey with regard to patients who dialyze nocturnally (LND) and for longer hours (LH). The patients experience will be presented in relation to their reason for modifying treatment, resultant changes in diet and medication prescription and their subjective experience of wellbeing. Findings indicate that patients who dialyse nocturnally and for longer hours experience improved sense of wellbeing, diet control and increased energy levels. While nocturnal dialysis does not suit all patients, the respondents in this survey reported benefits such as: increased opportunity for employment; less restrictions on free time; improved blood results and better lifestyle. PMID- 17345975 TI - Patient's sexual health: do we care enough? AB - It is well documented that sexual problems often accompany chronic health conditions, for example: chronic renal failure, hypertension and diabetes mellitus. One of the responsibilities of a nurse is to provide patients with information concerning their health and treatment to achieve optimum outcomes, thus enhancing patients' quality of life. However, the authors observed that the nursing clinical pathways in their practice seldom reflect the attention given to patient's sexuality. This paper aims to confirm the hypothesis that health professionals do not give sufficient care to patient's sexual health and to define the causes. A descriptive study consisted of close-ended questionnaire was employed. The medical and nursing staff of a Nephrology Department were included in the study (92.6% response rate). Professionals' opinions on the importance of patient's sexual health, difficulty in addressing this issue and attitude were explored. Staff's opinion on the importance of patient's sexual health is moderately high. However, 86% admit that they do not give sufficient attention and 92% never initiate to address sexual issues to patients. The results reveal the impediment being in relation to awkwardness and deficient sex education in dealing with this subject. Some staff have expressed other deterring factors. This study confirms that professionals do not render sufficient care to patient's sexual health due to their conservative attitude and lack of skill in addressing sexuality. The authors therefore suggest some ways in helping to bridge this gap. PMID- 17345976 TI - Multidisciplinary approach for prescriptive management of mineral and bone metabolism in chronic kidney disease: development of a dietetic led protocol. AB - BACKGROUND: A number of mineral metabolism abnormalities occur as kidney function declines, these include hyperphosphatemia, hyperparathyroidism and altered vitamin D metabolism. These derangements are associated with increased morbidity and mortality amongst the chronic kidney disease patient group. Treatment requires a multidisciplinary team approach in which the dietitian plays a pivotal role. OBJECTIVES: The development of protocols to aid implementation of various international, national and local treatment strategies is described. Audit the protocol to evaluate their clinical effectiveness. RESULTS: A prescriptive Protocol for the management of mineral and bone metabolism abnormalities in chronic kidney disease was developed and implemented. Initial audit findings suggest the protocol has had a positive effect on the control of phosphate, corrected calcium and parathyroid (PTH) levels. CONCLUSION: The development and implementation of a dietetic-led prescriptive therapy protocol allows dietitians and clinicians to adopt an integrated approach for the diagnosis and timely management of these complicated conditions. PMID- 17345977 TI - Dietary strategies to halt the progression of chronic kidney disease. AB - Chronic kidney disease is fast becoming a worldwide epidemic. There is an estimated annual increase of 8% with an associated economical and clinical burden. Recent research into lifestyle factors has confirmed different dietary attributes play a part in slowing the progression of chronic nephropathies. This has important implications and a potentially cost-saving way, to help reduce the progression of the disease. The roles of obesity, lipids, protein, diabetes and blood pressure are discussed to show how the current literature reflects how to modify the dietary aspects of these. The mechanisms behind these are not fully understood, but the message remains the same that there is an increased need for dietary advice in the pre-dialysis population. PMID- 17345978 TI - Re-training and switching of PD system to reduce recurrent gram-positive PD peritonitis. AB - Intensive training and re-education of peritoneal dialysis (PD) exchange technique has been advocated to minimize peritonitis rate. However, re-education of patients that are established on PD for some years can be difficult and a minority of patients on PD remain susceptible to repeated episodes of peritonitis. The UV Flash Compact system (Baxter Healthcare) automates patient connection and disconnection during the PD exchange procedure and uses bactericidal UV irradiation to minimise the effects of touch contamination. We have explored the efficacy of retraining patients using this system for reducing peritonitis rates in a cohort of 10 patients in who repeated episodes of peritonitis due to gram +ve organisms suggest irrevocable breaches in sterile technique. These patients were converted from their existing PD system (6 Staysafe [Fresenius Medical Care], 4 Mini-solo [Baxter]). Mean follow up post conversion was 10 months. There was a striking reduction in peritonitis caused by gram +ve pathogens from 1 in 8.5 to 1 in 50.5 months. Although it is not possible in this study to differentiate the impact of the UV Flash Compact as opposed to the effect of re-training, we advocate that patients with a high peritonitis burden from gram +ve organisms should be considered for conversion to the UV Compact system. PMID- 17345979 TI - Managing peritoneal dialysis (PD)--factors that influence patients' modification of their recommended dialysis regimen. A European study of 376 patients. AB - OBJECTIVES: The purpose of the study was to assess the prevalence and extent of missed peritoneal dialysis (PD) exchanges and to identify possible predictors for regimen modification. DESIGN: The study was a cross sectional postal survey of PD patients. Patients were asked to complete a single questionnaire looking at factors that influenced their management of the prescribed regimen. PATIENTS: 551 patients were invited to participate in the study from 17 centres across three European countries; 10 centres from Belgium, 5 from Italy and 2 from the UK. Patients on continuous ambulatory peritoneal dialysis (CAPD), CAPD and Quantum, or automated peritoneal dialysis (APD) for more than three months and at least 18 years old were included in the study. 376 out of 551 questionnaires were completed; a response rate of 68%. RESULTS: 20% (n=67) of those who responded to the questionnaire admitted to modifying their treatment in the previous month. Those who were more likely to modify their treatment were younger, employed, had greater contact with the PD team, were on APD 10 hours or longer and were less satisfied with their APD treatment. CONCLUSION: Many of the patients self reported modifying their dialysis regimen and possible predictors were highlighted from this study. By trying to identifying individual patients who do modify treatment healthcare professionals can target information that can support the patient in making safer treatment modification choices. PMID- 17345980 TI - Plasmapheresis in the treatment of acute vascular rejection: an experience on a dialysis unit. AB - Despite numerous the advances made in transplantation, acute rejection remains a major complication. Recent studies have shown that the use of plasmapheresis in the treatment of acute vascular rejection improves the chances of graft survival. In 1997 the plasmapheresis was transferred to the management of the renal unit, because we could offer a 24-hour service for all acute cases in our hospital. The number of cases has steadily increased, incorporating not only plasmapheresis, but also stemcellpheresis and red blood cell exchanges. Since July 2003, we have started using plasmapheresis in the treatment of acute vascular rejection in renal transplants. When a biopsy shows acute vascular rejection (A.V.R), combined with a decreased urine production, the patient commences therapy. Treatment consists of consecutive sessions, alternating between two sessions using saline/ albumin followed by one session using fresh frozen plasma. Depending on the lymphocyte count, therapy is carried out in conjunction with a course of Antithymocyte globulin (A.T.G.) between July 2003 and October 2004, 124 transplants were carried out, 15 suffered from acute rejection. Six were diagnosed with A.V.R, of these six; five were successfully treated with plasmapheresis and A.T.G. One patient only needed plasmapheresis to ensure a reversal of acute vascular rejection. We encountered no problem with the technique itself and although plasmapheresis seems to improve the outcome of graft survival, we need to ask ourselves, as demand increases: "Do we have the capacity to treat these patients on our unit in the future and is it our domain?" PMID- 17345981 TI - Blood pressure measurement. AB - Blood pressure measurement is the basis for the diagnosis, management, treatment, epidemiology and research of hypertension and the decisions affecting these aspects of hypertension will be influenced by the accuracy of measurement. Although blood pressure measurement is one of the most common clinical techniques, there are some factors affecting it, such as blood pressure variability or blood pressure measuring devices. Blood pressure can be measured in different ways: Clinic blood pressure measurement is taken in physician's office. The accurate measurement of blood pressure in clinical practice is dependent on the individual, the equipment used and the observer; this is the most common when considering therapeutic decisions. Self blood pressure measurement provides us with values on different days, in settings as close to daily life conditions as possible, having no white-coat effect. Ambulatory blood pressure measurement. With this method, using devices that permit the automatic monitoring of blood pressure in a patients normal life, health professionals are able to have blood pressure values over 24 hours, as well as the possibility of average blood pressure values over a requested period, such as the day or the night. PMID- 17345982 TI - Pre-dialysis education and patient choice. AB - The discussion was initiated by a paper on the influence of a pre-dialysis education programme on the mode of renal replacement therapy by Goovaerts et al (NDT 2005). Barriers to the uptake of self-care treatment modalities, including late referral, limited availability of treatment options, reimbursement, support from staff and families, the requirement for a helper and the length of the training programmes for home haemodialysis (HD) were discussed by 21 participants from 12 countries. The 'take-home' messages from the discussion were that to optimise the uptake of self-care modalities, renal units should try to ensure the all patients who are able to choose are fully informed before starting dialysis, even if they are referred to the unit very late. Offering a wide range of treatment options to new patients, and allowing (or encouraging) home HD without a helper, may also increase the number of patients who start and stay on a self care modality. It should be possible to provide an acceptable level of training, without compromising on safety, within 3 weeks if the patient is confident with needling. PMID- 17345983 TI - [Laparoscopy in emergency room: a new frontier?]. PMID- 17345984 TI - Sternal fracture with or without associated injuries. Assessment of the difference in the diagnosis, management and complications. Eighteen years of experience. AB - AIM OF THE STUDY: To determine the incidence of sternal fracture as an isolated injury as well as those which presented with concomitant injuries, and compare them in order to manage them more effectively. The Greek and International Literature related to the subject was also reviewed. MATERIAL AND METHODS: From 1984 to 2002 the Authors treated 134 patients with sternal fracture in the Department of Thoracic Surgery of their hospital, 59 males and 45 females, age from 17 to 84 years. Ninety patients had isolated sternal fracture and 44 sustained in addition fractured ribs, flail chest, pneumo-haemothorax, pneumo haemomediastinum, some of them experienced respiratory failure, vertebral fractures, myocardial infarction, heart contusion, pericarditis, head injuries, fractures of upper lower limbs and intraperitoneal bleeding. Twelve patients were admitted in ITU and 4 with multiple trauma were fatally injured. Aortic tears or ruptures didn't occur in any of our patients. Sternal fracture as an isolated injury has a better prognosis compared to those with associated injuries. CONCLUSIONS: The management of sternal fracture is usually conservative with a good outcome, provided early diagnosis and treatment of concomitant injuries is offered from a well-trained and experienced medical team. PMID- 17345985 TI - [Diaphragmatic traumas. Personal experience]. AB - OBJECTIVE: Diaphraghmatic injuries are rare (5-7%), usually secondary to blunt, or more rarely penetrating, thoracic or abdominal trauma. The most frequent site of trauma is the left postero-lateral region. We'll try to review this pathology in all its aspects. MATERIALS AND METHOD: We report our personal experience from January 2002 to December 2004 on 280 thoraco-abdominal trauma, 262 (93.5%) blunt and 18 (6.5%) penetrating, of which 5 (3.7%) interested the diaphragm. 4 following a blunt trauma and 1 an open trauma (gunshot) Each trauma was evaluated for possible associated injuries and for the type of symptoms at the admission and during the hospitalization. Preoperative diagnosis has been obtained only in 3 patients, haemodynamically stable. In the other 2 cases an emergency laparotomy was carried out because of their critic conditions and the diaphragmatic injuries were recognized during the procedure. Two patients died. CONCLUSIONS: We remark as during the acute phase the diaphragmatic rupture may be missed because of shock, respiratory insufficiency or coma of the patient; however, it's mandatory that the right diagnosis is reached as soon as possible in order that mortality is mostly influenced by the time elapsing between trauma and diagnosis. PMID- 17345986 TI - [Conservative and surgical treatment of esophago-gastric anastomotic leaks]. AB - OBJECTIVE: To evaluate the results of conservative and surgical management of esophago-gastric anastomotic leaks after esophagectomy for carcinoma. MATERIALS AND METHODS: A retrospective analysis of 510 patients subjected to esophagectomy and gastric pull-up with intra-thoracic or cervical anastomosis was performed. RESULTS: Twenty four cases (6.1%) of intra-thoracic anastomotic leaks and 17 (13.9%) cervical leaks were observed and treated. The conservative treatment was adopted in 19 intra-thoracic leakages (79%) and in 10 cervical leakages (59%). The leak-related mortality rate was 16.6% in patients with intra-thoracic leaks and 11.7% in those with cervical leaks. DISCUSSION: The introduction of staplers has dramatically decreased, but not eliminated, the risk of intra-thoracic and cervical anastomotic leaks. In our series the choice of the therapeutic approach was based on clinical and endoscopic findings. Patients with anastomotic dehiscence and gastric graft ischemia required reoperation, whereas conservative treatment was possible in the majority of cases. CONCLUSION: The treatment of esophago-gastric anastomotic leaks must be tailored to the individual patient. Early endoscopy is crucial for recognition of ischemia of the transposed stomach. PMID- 17345987 TI - Adjustable gastric banding for morbid obesity. Our experience. AB - BACKGROUND: The adjustable gastric banding is considered the most common procedure in Europe for the treatment of morbid obesity. We report our experience with this procedure, that was introduced in our Departments of Surgery since 1993. METHODS: From December 1993 to December 2004, 684 morbid obese patients (139 males and 545 females) underwent adjustable gastric banding (AGB) in our departments of Surgery. The first 323 patients were operated with perigastric procedure, the following 361 patients with pars flaccida technique. 601 patients were operated with laparoscopic approach, 83 with open approach. The average follow-up is 5 years. RESULTS: Mean BMI decreased from 42.2 to 34 Kg/m2 five years after the operation, with an EWL of 54 %. The main early complications were: intraoperative gastric perforation (5 patients, 1 of which repaired in laparoscopy); hemorrhage from short gastric vessels (3 patient, repaired in laparotomy). The major late complications were: intragastric band migration (7 patients); irreversible dilatation of the gastric pouch (42 patients, treated surgically with band removal or repositioning). CONCLUSION: In our experience laparoscopic adjustable gastric banding is a safe and effective procedure, suitable to most patients, and should be considered as the first choice in the surgical treatment of morbid obesity. PMID- 17345988 TI - [Laparoscopy in patients with colonic diverticulitis. Results of a prospectic data base]. AB - AIM OF STUDY: To evaluate the outcome of laparoscopic surgery in patients affected by colonic diverticulitis. MATERIALS AND METHODS: A prospective database was established in 1998 at our department to evaluate the results of laparoscopic treatment for diverticular disease. Contraindications to laparoscopic approach were: intestinal obstruction, faecal peritonitis, previuos major abdominal operations, presence of abdominal mass. Parameters evaluated were: indications to operation, age, sex, weight, type of operation, associated operations, operation time, conversion rate, mortality, post-operative complications, postoperative hospital stay, return to normal bowel function, time of removing nasogastric tube and time of restarting oral feeding. RESULTS: From 1998 to 2005, 109 patients operated for diverticular disease were registered. The operation was performed in 17 cases (15.5%) with open technique, in 20 cases (18.5%) throught video-assisted approach with extracorporeal anastomosis and in 72 cases (66%) with laparoscopic approach making intracorporeal anastomosis. The conversion rate was 10.8%. Mortality was 0%. In videolaparoscopic group mean operating time was 177 minutes, major complications were 4 (6.3%), minor complications were 6 (9.5%) and mean hospital stay was 7.8 days. In videoassisted group minor operation time was 158 minutes, complications were 9 (47.3%) and mean hospital stay was 10.1 days. CONCLUSIONS: Laparoscopic approach to diverticular disease of the colon is, in selected cases, a safe, feasible and effective procedure. PMID- 17345989 TI - [Diagnosis and treatment of retroperitoneal traumatic injuries. Our experience on 221 patients]. AB - BACKGROUND: The management of traumatic retroperitoneal injuries is still confusing to many surgeons. The presence of injuries of retroperitoneum generally worsens the prognosis in trauma patients and need more attention both the diagnosis and treatment and mortality is high comparated to abdominal traumati injuries. METHOD: A retrospective review was conducted of 221 patients with retroperitoneal injuries admitted to the Ospedale Maggiore Trauma Center in Bologna from 1989 to March 2005. RESULTS: Two hundred seven were blunt traumas and 14 penetrating. Mean age was 40.3; 25 patients died in operating room and 25 were treated with Damage Control Surgery for both abdominal and retroperitoenal injuries. The mortality rate was 15%. Data about surgical treatments, associate treatments for abdominal injuries, and need of reoperation are reported. CONCLUSION: Retroperitoneal traumatic injuries are challenging emergencies and need of attention and expertise by the suorgeon. Only with a careful judgement on the tactics and the procedure to carry on it is possible to gain valid results, which often means to safe the patients life. PMID- 17345990 TI - [The ultrasound microbubble contrast in the diagnosis and the decisional iter of the treatment of the traumatic spleen lesions]. AB - AIM OF THE STUDY: To estimate our 3-year experience on the diagnosis and monitoring of the spleen traumatic lesions with the employment of ultrasound microbubbles contrast. METHOD: From the 174 patients who were joints to our department in regimen of urgency for abdominal traumatic lesions, we have estimated 24 patiens including our criteria. The selected patients have been subordinate to the echographic examination with microbubbles contrast and to TC multi-detector (MDCT) with contrast with multiphasic technique. RESULTS: The echographic examination has evidenced 4 patients with abdominal fluid deposit without spleen parenchimal damage and 8 patients with morphofunctional alterations of the spleen. After the introduction of the contrast in 12 patients it has been evidenced a homogenous enhancement of the spleen parenchyma and in the remaining 12 patients the enhancement has turned out dishomogenous. From 24 patients examinated with CT with contrast, the traumatic breach of the spleen was demonstrated in same the 12 patients. CONCLUSION: It comes noticed the increased sensibility of the methodical CT with contrast and microbubbles contrast, that reaches up the 100% respect of the traditional echography whose sensibility turns out 66%. The CT remains the methodical gold-standard for the spleen traumatic lesions. Our experience suggests that the microbubbles contrast introduces the same one sensibility and it is preferred for follow-up and the corrected management of the patient. PMID- 17345991 TI - [Pathophysiological and clinical trials of the abdominal compartment syndrome]. AB - The abdominal compartment syndrome (ACS) is defined a situation of high degrade abdominal hypertension (IAH) with clinicals signs of multiorganic dysfunction. It's observed like in the intensive care, in particular surgycals and postraumatics, there is ever a bigger frequence of complications presented by criticals patients. The various trials remark a changeable incidence, but the common factor is characterized by a particular severity of scores. All the possibles mechanicals, haemorragicals, infiammatories, and postraumatics causes act, but don't enable the stability among abdominal content, abdominal compliance and parietal tension. The initial triad of effects is constitued by the elevation of diaphragm and the visceral and vascular compression; after this triad provoke a pathophysiologic system that, through various levels, bring to a respiratory, renal and cardiocirculatory dysfunction and to a parietal, hepatic and intestinal ischemia with consequent bacterical translation: sepsis and MOF. The Burch's classification (1996) report four levels of gravity by the slight (< 15 mmHg) to the heavyest (> 35 mmHg): the firsts two levels are of intensivistic competence and for the detention are used conservatives metodics and pharmacological approach; instead in the lasts two levels it's necessary to foresee a surgycal treatment of laparotomy, washing and drainage with following temporary paret's closure. The mortality is now very elevated (29-62%) especially when it's already established a multiorganical dysfunction; therefore it's necessary forward its appearance through the monitorization of abdominal pression (IAP) with the measurement of vescical pression in alls criticals patients at the aim to treat immediately the firsts signs of IAH. PMID- 17345992 TI - [Emergency thyroidectomy for primitive lymphoma of thyroid. Case report and diagnostic and therapeutic guidelines]. AB - OBJECTIVE: A case of acute wheezing causing primitive thyroid lymphoma observed ay the Operative Unit of General and Thoracic Surgery of the University "P Giaccone" of Palermo, Italy, is reported. EXPERIMENTAL DESIGN: Diagnostic, clinical and prognostic indication, evaluation of effectveness of radical surgical treatment and follow-up. INTERVENTION: Emergency radical surgical treatment (debulking) and surgical tracheostomy (tracheal infiltration). RESULTS: Complete recovery with "restitutio ad integrum". No relapse were recorded ad short follow-up. CONCLUSIONS: Total thyroidectomy in front of uncertain cytology with the suspect of Hashimoto' s treatment or acute wheezing or localized neoplasm (IE or IIE) is feasible and rationale. If possible, this treatment of choice must observe standard technique, with visualization and respect of four parathyroid glands and recurrent laryngeal nerves. This intervention has good prognosis and low morbidity and mortality in well experiences surgical teams of thyroid surgery. PMID- 17345993 TI - [Traditional techniques and experimental therapeutic approach for the restore of degenerate cartilages]. AB - Cartilage is unable to repair itself. The actual treatments for cartilage lesions primarily cover up symptoms only and this had led to develop alternative means to restore degenerated cartilage, above all by using cell therapy. The therapeutic approaches initially focused on the implantation of autologous chondrocytes, but this technique proved unsatisfactory. The discovery that several adult human tissues contain mesenchymal stem cells (MSCs) capable of differentiating into chondrocytes raised the possibility of using MSCs to repair cartilages. In the present study we investigated whether mesenchymal stem cells from adipose tissue (hADAS) are able to differentiate into cartilage cells. We isolated cells from lipoaspirates, characterized them detecting specific surface markers by FACS analysis and immunofluorescence. We differentiate hADAS towards condrogenic line in a culture media supplemented with some specific factors and in a specific condition called pellet culture. The isolation of hADAS cells is reproducible and characterized by an high reproductivity, non dependent from the donor age. The expression of surface markers suits with the literature data. The cells differentiated towards chondrogenic line in pellet culture show a different morphology from the undifferentiated cells. The potential application of MSC therapy provides new hope for the development of innovative treatments for the repair of cartilage lesions and disorders. PMID- 17345994 TI - [Post-traumatic acute appendicitis. A case report]. AB - Acute appendicitis is a frequent abdominal pathology, more frequent in the childhood. The pathophysiology of acute appendicitis is obstruction of the appendix lumen and distension due to continued mucosal secretion. The second step is a rapid multiplication of resident bacteria, excretion of toxine and wall inflammation. Causes of this processes are different: in most of cases there is an hyperplasia of intrinsic lymphoid tissue (60%) or hard stool. Another cause may be foreign body. But is there a relationship between abdominal trauma and appendicitis? PMID- 17345995 TI - Giant epidermoid cyst of the spleen with carbohydrate and cancer antigen production managed laparoscopically. AB - True cysts of the spleen are rare; in a few cases, high serum levels of carbohydrate and cancer antigen have been reported. In such instances, cyst resection or splenectomy is indicated to rule out malignant lesions and to remove the cancer antigen producing epithelium. We report the case of a young woman with a symptomatic giant epidermoid cyst of the spleen. Due to the secreting epithelium lining the cyst, serum levels of CA 19-9 and CA 125 were elevated. Laparoscopic splenectomy achieved symptoms relief and and long-term normalization of serum tumor markers. PMID- 17345996 TI - [Late cutaneous fistula after inguinal hernia repair. A case report]. AB - A late inflammatory reaction and the formation of fistula after prostetic implant for primitive hernia of the abdominal wall are recent clinical events. The Authors describe a case of inguinal cutaneous fistula verified after 6 years from the execution of an prostetic hernioplasty with polypropylene. The possible etiology and the therapeutic options are discussed. PMID- 17345997 TI - [The formation of an emergency service surgeon]. PMID- 17345998 TI - [Enamel fluoride uptake following fluoride application and fluoride precipitation]. AB - This study is on fluoride uptake into enamel following fluoride precipitation with calcium hydroxide. Five specimens each from 12 bovine incisors were polished, covered with a salivary pellicle, and distributed into five groups (n=12). A fluoride solution (43,500 ppm F from magnesiumfluorosilicate, copper (II)-fluorosilicate and sodium-fluoride, pH 2; Tiefenfluorid Touchierlosung, Humanchemie) and Ca(OH)2-solution (Tiefenfluorid Nachtouchierlosung) were applied subsequently in group TN. "Touchierlosung" only was used in group T, sodium fluoride (43,500 ppm F, pH 2) in group NaF, and aminefluoride (Elmex fluid, 10,000 ppm F, pH 4) in group EF. No fluoride was used in group NK (negative control). Following rinsing and 24 h storage in artificial saliva surface KOH soluble fluoride content (KOHF), and structurally bound fluoride content (SBF) from three layers (0-33, 33-66 and 66-99 pm) was determined by fluoride electrode procedures. KOHF (median in microg/cm2) of NK was below the lower limit of quantification of the fluoride electrode. The other group values were significantly higher (Mann-Whitney test, p < or = 0.05). TN (1.6), T (1.4) and NaF (1.1) did not differ significantly. EF (0.6) was significantly smaller than TN and T but not smaller than NaF. SBF (0-33, 33-66, 66-99 pm; median in microg/cm3) of TN (445, 341, 275), T (644, 481, 360), NaF (804, 480, 307) and EF (449, 346, 280) did not differ significantly but, with the exception of TN, were significantly higher as compared to NK. A precipitation reaction with Ca(OH)2 following fluoridation did not increase enamel fluoride uptake. PMID- 17345999 TI - Subjectivity and examiner experience in diagnosis of residual caries--an in vitro study. AB - The aim was to evaluate subjectivity (using inter- and intraexaminer repeatability), the effect of examiner experience, and residual caries diagnostic accuracy with visual tactile (VT) criteria and using a caries disclosing agent (CD). Thirty teeth with occlusal caries were excavated by a single operator not involved in the diagnostic part of the study. A test area was marked in each cavity. Four dentists with more than five and five dentists with less than five years' experience rated the marked area twice (a week apart) using VT criteria. A week later, the samples were stained using Caries Detector. The same examiners rated the presence or absence of stain in the marked area twice (a week apart). Undecalcified thin slices were examined for bacteria using light microscopy. Overall kappa for inter-examiner repeatability was higher for CD (0.45) than VT (0.31). In the less experienced group the kappa value was higher for CD (0.41) than for VT (0.23). In the experienced group kappa was lower for CD (0.43) than for VT (0.46). Median kappa for intra-examiner repeatability was higher for caries detector (0.77, 0.53) compared to visual tactile (0.52, 0.34) for the more and less experienced examiners respectively. There was no significant difference between the experienced and the inexperienced group in combined sensitivity and specificity (mean) for VT (0.52, 0.53) or CD (0.60, 0.58). IN CONCLUSION: VT was more subjective than CD, except for experienced examiners who had a higher inter examiner repeatability for VT than CD. Diagnostic accuracy for residual caries does not increase with experience. PMID- 17346000 TI - [Injuries to permanent teeth. Part 3: Therapy of root fractures]. AB - Diagnostic and therapeutic interventions following dental injuries are not part of the routine practice in the dental office. Quite often, these patients are emergency cases who seek treatment after normal office hours. The objective of this and the future papers is to present the current treatment concepts in dental traumatology at the School of Dental Medicine, University of Berne. The fruitful cooperation in the field of dental traumatology between the Department of Oral Surgery and Stomatology, and the Department of Conservative Dentistry (including pediatric dentistry and endodontology), is based on the interdisciplinary approach that has been established four years ago. Following discussion and evaluation of such treated cases, and considering current clinical and experimental studies, the said concepts have been worked out. The present paper describes the therapeutic approach for root fractures. PMID- 17346001 TI - [Impact of tobacco use on the periodontium--an update. Part 2: Clinical and radiographic changes in the periodontium and effects on periodontal and implant therapy]. AB - This third part of a series of publications from the Swiss task force "Smoking- Intervention in the private dental office" on the topic "tobacco use and dental medicine" describes the clinical and radiographic changes of the periodontium within smokers as well as the consequences of tobacco use on periodontal and implant therapy. With increased use of tobacco, patients show higher periodontal probing depths, increased clinical attachment loss, more alveolar bone resorption, a higher prevalence of gingival recessions, and a higher risk for tooth loss. In contrast to this, with smokers, the clinical characteristics of gingival inflammation or bleeding on periodontal probing are less established. Smokers show less positive results after conventional, surgical and regenerative periodontal therapy. The benefits of mucogingval surgery are reduced and less successful in smokers. Moreover, smoking impairs the osseointegration of oral implants and is at least partly responsible for a majority of biological complications in implant dentistry, such as periimplantitis. Based on the present understanding of periodontal diseases, the clinical findings, and the specific therapeutic outcomes with smokers, it appears to be reasonable, next to the current classification of periodontal diseases, to use the term "smokers periodontitis". PMID- 17346002 TI - Waste management and recycling practices of the urban poor: a case study in Kuala lumpur city, Malaysia. AB - This study assesses waste management and recycling practices of the urban poor households residing as squatters and in low-cost flats of Kuala Lumpur city, Malaysia. To attain the objective, the study employed some statistical techniques such as t-tests of equality of means, one-way analysis of variance, chi-squared 'likelihood ratio' tests, and simple descriptive statistics. The statistical techniques were used to determine and analyse the factors that significantly influence the environmental behaviour of the urban poor concerning solid waste management, particularly their recycling practices. The findings of the study show that the urban poor and low-income communities have been proved to behave in ways that are consistent with and conducive to environmentally friendly solid waste management. This study provides evidence that the urban poor and low-income communities are the main recyclers, re-users, and source-reducers of their household solid waste. The study, however, suggests that policies should be formulated to focus on promoting knowledge, education, and the skills of the urban poor and, in addition, to empower them as a means of improving their quality of life. PMID- 17346003 TI - Interaction of potato production systems and the environment: a case of waste water irrigation in central Washington. AB - Potato production and processing are very important activities in the agricultural economy of the Pacific Northwest. Part of the reason for the development of this industry has been the availability of water for both growing and processing. A great amount of water is used in processing potato products, such as frozen French fries, and the waste water is a pollutant because it contains high levels of nitrate and other nutrients. Using this waste water to irrigate the fields can be a suitable disposal method. Field application will reduce potato fertilizer costs, but it can also cause underground water contamination if over-applied to the field. In this econometric study, we used field data associated with current waste water applications in central Washington to examine the yield response as well as the soil nitrogen content response to waste water applications. Our results from the production model show that both water and nitrogen positively affect crop yields at the current levels of application, but potassium has been over applied. This implies that replacing some waste water with fresh water and nitrogen fertilizer will increase production. The environmental model results show that applying more nitrogen to the soil leads to more movement below the root zone. The results also suggest that higher crop yields lead to less nitrogen in the soil, and applying more water increases crop yields, which can reduce the nitrogen left in the soil. Therefore, relative to the current practice, waste water application rates should be reduced and supplemented with fresh water to enhance nitrogen use by plants and reduce residual nitrogen in the soil. PMID- 17346004 TI - Microbial C and N dynamics during composting process of urban solid waste. AB - Microbial characterization of composting is of importance for the optimization of the process and the quality of the end product. The aim of this work was to follow microbial biomass C and N dynamics during the composting process of urban solid waste. Microbial biomass C (B(C)) ranged from 4.06 to 1 microg kg(-1) of dry compost from day 5 to day 62 and decreased to reach 0.44 mg kg(-1) in mature compost. Microbial biomass N (B(N)) showed the same trend as B(C), ranging from 1.472 to 0.443 microg kg(-1) of dry compost from day 5 to day 62. This behaviour is probably related to the decreasing availability of readily decomposable substrates with the ongoing of the process. B(C) and B(N) showed a strong correlation (r = 0.78). The dynamics of the B(C)/B(N) ratio, index of the chemical composition of the whole microbial population suggested a shift in the composition of microbial populations during the process from prevailing bacteria and actinomycetes to prevailing fungi. PMID- 17346005 TI - Optimization of anaerobic digestion of municipal solid waste in combined process and sequential staging. AB - The optimization of anaerobic digestion aims to maximize organic waste stabilization after a short digestion period. This paper presents the optimization performance of the combined anaerobic digestion and sequential staging concept in a thermophilic, solid-state batch system as a treatment technology prior to landfill. The former involves enhanced pre-stage flushing with the addition of microaeration and inoculum in the methane phase. The latter involves leachate cross-recirculation between the mature and fresh waste reactors without conducting a pre-stage operation. The optimized process for combined anaerobic digestion showed that reducing the pre-stage operation with the maximum removal of organics from the waste bed is beneficial. Moreover, the sequential staging concept offers an improved process over the combined anaerobic digestion wherein the specific methane yield of 11.9 and 7.2 L CH4 kg(-1) volatile solids (VS) per day was achieved, respectively. After 28 days of operation, the sequential staging process showed an improved waste stabilization with 86 and 79% mass and volume reduction, respectively. A higher methane yield of 334 L CH4 kg( 1) VS with 86% VS reduction, which is equivalent to 84% process efficiency was obtained. PMID- 17346006 TI - Emissions from baled municipal solid waste: I. Methodological approach for investigation of gaseous emissions. AB - This paper presents a methodological approach for the study of volatile organic compounds (VOCs) in air, emitted during storage of municipal solid waste in bales. Determination of VOCs was based on sampling with adsorbent tubes followed by automated analysis using on-line work-up with a thermal desorption unit directly connected to a gas chromatograph-mass spectrometer. Using calculation algorithms and multidimensional statistical analysis of large amounts of data collected, the information was compressed and visualized. The approach was applied to initial measurements of emissions of VOCs from 24 bales composed of municipal solid waste, each bale stored in a wooden box. These bales were produced using the two types of baling equipment available, resulting in cylindrical or rectangular bales, with different densities. Hundreds of different VOCs emitted from these bales sorted out into groups with different chemical structure. Differences in VOC concentrations in air were found between wastes stored in cylindrical or rectangular bales. For instance, it was found that the concentration of VOCs (relative to the concentration of toluene), in the first experiment after storing, for cylindrical bales with six layers of LDPE was 115 +/- 10 microg m(-3), while for rectangular bales it was only 64 +/- 8 microg m( 3). The procedure used for data interpretation suggested different degradation mechanisms in different types of bales. The use of multiple data interfaces, multidimensional statistics and automated chemical analysis methods are likely to be more and more common for waste companies and waste research in the near future. This is due to the interdisciplinary nature of the subject that relies heavily on various areas of science and information technology. PMID- 17346007 TI - Dense resistivity and induced polarization profiling for a landfill restoration project at Harlov, Southern Sweden. AB - A resistivity and time-domain induced polarization (IP) survey was conducted at a landfill site under restoration at Harlov in Southern Sweden. The covering of the landfill had begun some years ago, without keeping precise records of the work done, as is usual in such procedures. The survey was conducted in two steps, on two adjacent areas. First, a number of geoelectrical sections were made on a partly covered area that had been investigated earlier by auger drilling, in order to assist restoration. Then, a second area that should have received its final cover was imaged, and some defects in the cover could be detected and repaired. The resistivity and time-domain IP results were consistent with the results of the geotechnical drillings, and they enabled quasi-continuous mapping along the profiles. Three-dimensional visualization showed the overall consistency of the two-dimensional lines, and helped to generate a global view of the site. In spite of some ambiguities, cover and waste could be distinguished in most cases. In particular, fine-grained cover materials could be clearly distinguished from other cover materials. PMID- 17346008 TI - The controlling of landfill leachate evapotranspiration from soil-plant systems with willow: Salix amygdalina L. AB - The use of willows (Salix amygdalina L) to manage landfill leachate disposal is an effective and cost-effective method due to the high transpiration ability of the willow plants. A 2-year lysimetric experiment was performed to determine an optimum leachate hydraulic loading rate to achieve high evapotranspiration but exert no harmful influence on the plants. The evapotranspiration rate of a soil plant system planted with the willow was 1.28-5.12-fold higher than the rate measured on a soil surface lacking vegetation, suggesting that soil-willow systems with high volatilization rates are a viable landfill leachate treatment method. Of the soil-willow systems, the one with willow growing on sand amended with sewage sludge soil at an hydraulic loading rate of 1 mm day(-1) performed best, with evapotranspiration ranging from 2.25 to 3.02 mm day(-1) and a biomass yield of 8.0-9.85 Mg dry matter ha(-1). The organic fraction of the soil increased as much as 2.5% of dry matter, due to the sewage sludge input, which exerted a positive effect on the biomass yield as well as on transpiration and evaporation. It was observed that the plants in the sand-and-sewage sludge soil systems displayed higher resistance to toxic effects from the applied landfill leachate relative to plants in the sand-soil systems. PMID- 17346009 TI - Use of waste rubber as concrete additive. AB - For resource reutilization, scrap tyres have long been investigated as an additive to concrete to form 'Rubcrete' for various applications and have shown promising results. However, the addition of rubber particles leads to the degradation of physical properties, particularly, the compressive strength of the concrete. In this study, a theoretical model was proposed to shed light on the mechanisms of decrease in compressive strength due to the addition of rubber particles as well as improvement in compressive strength through modification of particle surfaces. The literature suggests that the compressive strength can be improved by soaking the rubber particles in alkaline solution first to increase the inter-phase bonding between the rubber particles and cement. Instead, we discovered that the loss in compressive strength was due to local imperfections in the hydration of cement, induced by the addition of heterogeneous and hydrophobic rubber particles. Microscopic studies showed that the rubber particles disturbed the water transfer to create channels, which were prone to cracking and led to a loss in the compressive strength. Unexpectedly, no cracking was found along the surfaces of the rubber particles, indicating that the bonding strength between the rubber particles and cement phases was not the critical factor in determining the compressive strength. Therefore, a theoretical model was proposed to describe the water transfer in the Rubcrete specimens to explain the experimental data. In the model, the local water available for hydration (Q) is: Q = -A(slv)/6piv, where Q, A(slv), and v are mass flow rate (kg s(-1)), Hamaker constant (J), and dynamic viscosity (m2 s(-1)), respectively. By maximizing the quantity Q and, in turn, the Hamaker constant A(slv), the compressive strength could be improved. The Hamaker constant A(slv) for water film on rubber particle surfaces was smaller than that for the hydrated cement particles; the water transfer rate was lower in the presence of rubber particles because the Hamaker constant A(slv) for water film on rubber particle surfaces was smaller than that on the hydrated cement particles. Thus, the compressive strength of Rubcrete could be improved by increasing the Hamaker constant of the system. This was achieved by increasing the refractive indices of the solids (n(s)). The refractive indices of materials increase with increases in functional groups, such as OH and SH on the surface. The model provided a possible mechanism for the efficacy of treating rubber particles with NaOH in improving the compressive strength. By using NaOH solution treatment, an oxygen-containing OH group was formed on the rubber surface to increase the Hamaker constant of the system, leading to higher compressive strength. Based on this mechanism, a novel method for modification of the rubber particles was also proposed. In this process, the rubber particles were partially oxidized with hot air/steam in a fluidized bed reactor to produce the hydrophilic groups on the surface of the particles. Preliminary results obtained so far are promising in accordance with the theory. PMID- 17346010 TI - Sinterability study of ceramic bodies made from a mixture of mineral coal bottom ash and soda-lime glass cullet. AB - The aim of this study was to investigate the sinterability to improve the technical properties of ceramic bodies made from coal bottom ash and soda-lime glass cullet. Different mixtures of bottom ash and glass cullet were formulated. The amount of bottom ash was 100, 70, 50 and 30 wt.%. The particle size distribution was the same for all formulations. The mixture containing 50 wt.% bottom ash also had its particle size distribution changed. Samples were formed by dry pressing and then fired at 950, 1050 and 1150 degrees C. Samples were evaluated for linear shrinkage, water absorption, flexural mechanical resistance, scanning electronic microscopy, pyroplastic deformation and thermodilatometric analysis. The higher firing temperature led to a decrease in water absorption and increased linear shrinkage, mechanical resistance and pyroplastic deformation. This effect was also observed for addition of glass up to 50 wt.%. The effect of smaller particles of bottom ash was more significant for linear shrinkage and mechanical resistance of ceramic bodies fired at 1150 degrees C. The use of a finer powder contributed to increase these properties. The influence of finer particles on water absorption and mechanical resistance of ceramic bodies fired at 950 and 1050 degrees C was not significant. PMID- 17346011 TI - Treatment and disposal alternatives for health-care waste in developing countries -a case study in Istanbul, Turkey. AB - Efficient health-care waste management is crucial for the prevention of the exposure of health-care workers, patients, and the community to infections, toxic wastes and injuries as well as the protection of the environment (Safe Management of Wastes from Health-care Activities. World Health Organization, Geneva). The amount of health-care waste produced in the Istanbul Metropolitan City in Turkey is 30 ton day(-1) in total. The method used for the final disposal of most of the health-care waste of Istanbul is incineration. However, a great portion of the infectious waste is disposed of with the domestic waste into the sanitary landfill because of improper segregation practices applied in the health-care institutions. Therefore the alternatives for the treatment and disposal of health care waste were evaluated. The technical information related to the available treatment technologies including incineration, microwave irradiation, mobile or stationary sterilization, etc. were also investigated. The capital investment cost, transportation/operational costs for each alternative method and the different locations for installation were compared. When the data collected were evaluated, it was found that separate handling and disposal of health-care waste generated on the European and the Asian sides of the city was the most economic and practicable solution. As a result, it was concluded that the capacity of the Kemerburgaz-Odayeri incineration plant is enough to incinerate the health-care waste generated on the European side of Istanbul, the construction of a new incineration plant or a stationary sterilization unit for the disposal of health care waste generated on the Asian side was the most effective alternative. PMID- 17346012 TI - Characterization of a thermal power plant air heater washing waste: a case study from Iran. AB - In Iran most of the electricity is generated by thermal power plants. As a result of fuel oil burning in winter time, the air heaters of the boilers have to be washed and cleaned frequently. The wastewater originating from air heater washing is then treated in an effluent treatment plant by chemical precipitation followed by dewatering of the sludge produced. The resulting waste is classified as specific industrial waste that should be characterized in detail under the Waste Management Act of Iran. The quantity of this waste produced in the studied power plant is about 20 tonnes year(-1). In the present investigation, the first to be carried out in Iran, seven composite samples of dewatered sludge from air heater washing wastewater treatment were subjected to investigation of the physical properties, chemical composition and leaching properties. The most likely pollutants that were of concern in this study were heavy and other hazardous metals (Cd, Co, Cr, Mn, Ni, Pb, Zn and V). The results revealed that mean pH, wet and dry density and moisture content of the waste were 6.31, 1532 kg m(-30, 1879 kg m(-3) and 15.35%, respectively. Magnetite, SiO2, P2O5, CaO, Al2O3 and MgO were the main constituents of the waste with a weight percentage order of 68.88, 5.91, 3.39, 2.64, 2.59 and 1.76%, respectively. The toxicity characteristic leaching procedure test results for some heavy and other hazardous metals showed that mean elemental concentrations of Cd, Co, Cr, Mn, Ni, Pb, V and Zn in leachate were 0.06, 1.55, 5.49, 36.32, 209.10, 0.58, 314.06 and 24.84 mg L(-1), respectively. According to the Waste Management Act of Iran this waste should be classified as hazardous and should be disposed of in accordance with hazardous waste disposal regulations. PMID- 17346014 TI - Not hungry? No problem. PMID- 17346013 TI - The stage of grief no one admits to: relief. PMID- 17346015 TI - Patients need specialist, sponsored nursing posts. PMID- 17346016 TI - Are specialist nurses in wound care corrupt? PMID- 17346018 TI - Survey of student nurses and midwives: smoking and alcohol use. AB - This article presents findings from a survey of 186 first year nursing and midwifery students that relate to their smoking and alcohol consumption. Of the students sampled, 28% were cigarette smokers. This is higher than the smoking rate of 25% for the adult population in the UK. The majority of the students who smoked said that they would like to stop smoking. Most of the students (86.5%) reported having drunk alcohol on at least one occasion during the previous week, with 26.5% having had a drink on three or four days. The amount consumed over the week ranged from no drinks to 90, with the mean being 13.72.Worryingly, 74% had exceeded the daily benchmarks for low-risk drinking on at least one occasion during the week for which consumption was reported, and 55% were drinking at binge levels. The findings raise concerns for the future health of many of our students and for their roles as health promoters. PMID- 17346019 TI - Part 1: nurses' guide to alcohol and promoting healthy lifestyle changes. AB - In the first of three articles we consider the mechanisms by which alcohol affects the human body and mind. In subsequent articles we will examine the impact of alcohol on health and social wellbeing and the support and health promotion measures that the nurse might use to assist patients. Alcohol has distinctive effects on physiology that are mediated by gender and the level of exposure to the drug over time. In this article we consider the ways in which alcohol acts as a mental stimulant and then as a depressant, and we examine how exposure reinforces further alcohol consumption. Consideration is given to how alcohol is metabolized and how it may then interact with other drugs within the body. PMID- 17346020 TI - Prontosan wound irrigation and gel: management of chronic wounds. AB - Chronic wounds present a challenge that is costly in terms of quality of life to the patient and in financial terms for the NHS. Several factors contribute to the development of a chronic wound, in particular the influence of bacteria as a biofilm within the wound environment. Irrigating a wound with normal saline has long been advocated as the most appropriate method of wound irrigation but biofilms are now known to be resistant to this method of cleansing. A small (10 patient) evaluation of the use of Prontosan in patients whose duration of chronic wounds exceeded 1 year has demonstrated that Prontosan wound irrigation and Prontosan gel are an appropriate alternative for cleaning, moistening and decontaminating encrusted, contaminated and chronic skin wounds, and can have a dramatic influence of the quality of life for such patients. This article discusses the cause of chronicity within a wound and discusses in depth three of the ten patients in the evaluation. PMID- 17346021 TI - How accurate are RGNs in grading pressure ulcers? AB - This study investigated the level of accuracy with which qualified nurses grade pressure ulcers. The sample of the study was 52 registered general nurses (RGNs) who worked at an acute NHS Trust. The study was conducted as a series of workshops in which questionnaires were administered before and after an educational programme on the theory and practice of grading pressure ulcers. The instrument of measure was a set of 20 photographs of various grades of pressure ulcers and incontinence lesions. At the end of the data collection process 52 sets of data were available and included for analysis (n=52). The level of accuracy of the RGNs in grading pressure ulcers was poor in the pre-test. Although it improved markedly at the post-test, the overall performance of the group remained less than satisfactory (between 80-100% correct answers). In the post-test, only 4 out of the 52 (7.7%) RGNs achieved a level of accuracy between 75% to 95%. The limitation of the study means that caution is needed in making inferences of the findings beyond this sample of nurses. However, the study's findings do give some indication of the level of accuracy of pressure ulcer grading within the Trust concerned. A larger scale study is needed if a more reliable picture on the accuracy of pressure ulcer grading by RGNs is to be achieved. PMID- 17346022 TI - Developing a perspective on restraint and the least intrusive intervention. AB - This article explores contemporary practice in the use of restraint in the light of recent European Council Guidance endorsing the principles of least restrictive environment/least intrusive intervention. Violence is a source of concern in many European mental health services but approaches to its immediate management continue to display remarkable diversity reflecting the adoption of differing perspectives on what constitutes 'least intrusiveness'. This article examines the basis for practice in terms of the range of procedures available, reviews the literature on restraint safety and presents a model based on the concept of reasonableness which can be used to evaluate whether a given intervention meets the European guidance. Current practice across Europe is largely a function of tradition and local values rather then evidence based. Collaborative large-scale studies are required to determine the relative risks of the range of interventions in use such that practice is informed by evidence rather than opinion. PMID- 17346023 TI - Pressure ulcer care: making and handling a complaint in the NHS. AB - This article considers a case where a patient is suffering from a pressure ulcer and there is a dispute between hospital and care home as to its cause. It looks at the handling of a complaint under the new NHS Regulations and in a care home. PMID- 17346024 TI - Audit of peripheral venous cannulae by members of an i.v. therapy forum. AB - This article describes a clinical audit of peripheral venous cannulae (PVC) undertaken by members of a national intravenous therapy forum. PVC care was reviewed using the RCN 'Standards for Infusion Therapy' and the Department of Healh's 'Winning Ways' report, action area 2 (DH, 2003; RCN, 2003) to define best practice. Data were collected by members of the forum and submitted for analysis by the members' coordinator. The findings of the audit highlighted several areas for improvement in PVC care. The most significant finding was poor documentation of the insertion of the cannula. An additional concern was that the person who performed the cannulation could not be identified for 236 (37.7%) of PVC audited. Draft recommendations with strategies for implementation have been proposed and feedback sought from participants with plans to re-audit in 2007. PMID- 17346025 TI - Preparing for practice: how well are practitioners prepared for teamwork. AB - This article reports on the findings of a study that aimed to explore how relevant initial training is in relation to teamwork, and to explore the perceptions of newly qualified practitioners about their confidence to work as a member of a team. A cross-sectional postal survey was used to ascertain the views of nurses, social workers, occupational therapists and physiotherapists who had been qualified between six months and two years prior to the survey, and had qualified at one of three London universities. Fifty questionnaires were sent out to each professional group (a sample of 200 overall) and there was a 43% response rate. Findings revealed that respondents reported positive experiences of team working, with only one area--equality of status within teams--being highlighted as problematic. While no other area generated this level of disagreement, there were two other areas in which respondents felt unsure: cooperation within the team and conflict resolution within the team. PMID- 17346026 TI - Assessment of altered conscious level in clinical practice. AB - This article will critically appraise the literature focusing on the use and application of the Glasgow Coma Scale (GCS). Historically the GCS tool was created in a 14-point format and later revised to a 15-point format. Critical analysis of this potentially confusing aspect will be explored. The GCS tool enables the healthcare practitioner to effectively monitor the level of consciousness. The authors believe that anatomical and physiological knowledge is required to competently interpret assessment of level of consciousness. The article will review the anatomical basis of consciousness and consider some of the issues of application of GCS in practice, including painful stimuli. PMID- 17346027 TI - Preserving sexuality in mixed-sex wards. PMID- 17346028 TI - Preclinical evaluation of MORAb-003, a humanized monoclonal antibody antagonizing folate receptor-alpha. AB - The highly restricted distribution of human folate receptor-alpha (FRalpha) in normal tissues and its high expression in some tumors, along with its putative role in tumor cell transformation, make this antigen a suitable target for antigen-specific, monoclonal antibody-based immunotherapy for oncology indications. We have developed a therapeutic humanized monoclonal antibody with high affinity for FRalpha, named MORAb-003, which was derived from the optimization of the LK26 antibody using a whole cell genetic evolution platform. Here we show that MORAb-003 possesses novel, growth-inhibitory functions on cells overexpressing FRalpha. In addition, MORAb-003 elicited robust antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in vitro, and inhibited growth of human ovarian tumor xenografts in nude mice. Because of its multimodal activity in vitro and its safe toxicology profile in non-human primates, MORAb-003 development has recently been advanced to clinical trials involving ovarian cancer patients. PMID- 17346029 TI - Highly efficient synthesis of azabicyclo[x.y.0]alkane amino acids and congeners by means of Rh-catalyzed cyclohydrocarbonylation. AB - A highly efficient method for the synthesis of 1-azabicyclo[x.y.0]alkane amino acid derivatives and their congeners by means of extremely regioselective cyclohydrocarbonylation (CHC) is described. The CHC reactions are catalyzed by Rh BIPHEPHOS complex under mild conditions. These CHC reaction processes involve (i) an extremely linear-selective hydroformylation of the terminal alkene moiety of a dehydrodipeptide substrate, (ii) intramolecular condensation to form cyclic N acyliminium key intermediate, and (iii) the second cyclization through intramolecular nucleophilic addition of a heteoatom nucleophile to the cyclic N acyliminium moiety to afford the corresponding 1-azabicyclo[x.y.0] system. This consecutive double cyclization process proceeds with extremely high diastereoselectivity in most cases. This method has been successfully applied to the syntheses of 1-azabicyclo[4.4.0], -[5.4.0], and -[4.3.0] systems. The mechanisms of the reactions and the rationale for the observed extremely high diastereoselectivity are presented. This Rh-catalyzed CHC process would serve as a highly efficient and versatile method for the syntheses of a variety of conformationally restrained dipeptides, peptidomimetics, alkaloids, and other biologically active natural or unnatural products. PMID- 17346030 TI - Releasable PEGylation of mesothelin targeted immunotoxin SS1P achieves single dosage complete regression of a human carcinoma in mice. AB - Recombinant immunotoxins exhibit targeting and cytotoxic functions needed for cell-specific destruction. However, antitumor efficacy, safety, and pharmacokinetics of these therapeutics might be improved by further macromolecular engineering. SS1P is a recombinant anti-mesothelin immunotoxin in clinical trials in patients with mesothelin-expressing tumors. We have modified this immunotoxin using several PEGylation strategies employing releasable linkages between the protein and the PEG polymers, and observed superior performance of these bioconjugates when compared to similar PEG derivatives bearing permanent linkages to the polymers. PEGylated derivatives displayed markedly diminished cytotoxicity on cultured mesothelin-overexpressing A431-K5 cells; however, the releasable PEGylated immunotoxins exhibited increased antitumor activity in A431-K5 xenografts in mice, with a diminished animal toxicity. Most significantly, complete tumor regressions were achievable with single dose administration of the bioconjugates but not the native immunotoxin. Pharmacokinetic analysis of the releasable PEGylated derivatives in mice demonstrated an over 80-fold expansion of the area under the curve exposure of bioactive protein when compared to native immunotoxin. A correlation in degree of derivatization, release kinetics, and polymer size with potency was observed in vivo, whereas in vitro cytotoxicity was not predictive of efficacy in animal models. The potent antitumor efficacy of the releasable PEGylated mesothelin targeted immunotoxins was not exhibited by similar untargeted PEG immunotoxins in this model. Since the bioconjugates can also exhibit the attributes of passive targeting via enhanced permeability and retention, this is the first demonstration of a pivotal role of active targeting for immunotoxin bioconjugate efficacy. PMID- 17346031 TI - General in vivo assay for the study of integrin cell membrane receptor microclustering. AB - A method for measuring the microclustering of a class of cell surface receptors called integrins is reported. Integrins are proteins involved in bidirectional signaling across the cell membrane and are important in cell adhesion, growth, and survival. Their activity is regulated by changes in protein conformation and protein clustering. The developed in vivo clustering assay uses fluorescence resonance energy transfer (FRET) and has the benefit of requiring a single cloning step to generate FRET donors and acceptors that can be used to measure the clustering of a series of integrin mutants. The FRET reporters contain extracellular donor or acceptor fluorescent protein attached to native integrin cytoplasmic and transmembrane domains, and these are expressed along with wild type or mutant integrins. Expression of the FRET reporters has no affect on the ligand binding properties of coexpressed integrins. FRET values are calculated for cell lines spreading on ligand coated surfaces, and these values are independent of fluorescent protein expression. No FRET is observed in cell lines expressing the reporters in the absence of integrins. Integrin-dependent FRET values increase approximately 2-3-fold when the integrins contain mutations that result in increased ligand binding affinities. PMID- 17346032 TI - Synthesis of proteins containing modified arginine residues. AB - Unnatural amino acid mutagenesis provides the wherewithal to study protein function in great detail. To extend the repertoire of functionalized amino acids available for study by this technique, seven structural analogues of arginine were prepared and used to activate a suppressor tRNACUA. These included Ngamma methylarginine, Ngamma-nitroarginine, citrulline, homoarginine, and three conformationally constrained analogues based on proline. These misacylated tRNAs were shown to be capable of introducing the arginine analogues into dihydrofolate reductase (position 22) and Photinus pyralis luciferase (positions 218 and 437). Most of the modified luciferases containing arginine analogues at position 218 emitted light with less efficiency and at longer wavelength than the wild type. This is consistent with the postulated role of this residue as essential for maintaining the polarity and rigidity of the luciferin-binding site. Interestingly, the luciferase containing Ngamma-methylarginine at position 218 emitted light at the same wavelength as the wild type and was at least as efficient. Alteration of the arginine residue at position 437 had no effect on the wavelength of emitted light but afforded analogues, all of which emitted light less efficiently than the wild type. This is altogether consistent with the putative role of Arg437, which is an invariant residue within the superfamily of enzymes that includes P. pyralis luciferase. This amino acid is part of the linker between the two structural domains of luciferase that is believed to be essential for efficient enzyme function but not part of the substrate-binding site. PMID- 17346033 TI - Characterization and analysis of early enzymes for petrobactin biosynthesis in Bacillus anthracis. AB - Recently, iron acquisition and, more specifically, enzymes involved in siderophore biosynthesis have become attractive targets for discovery of new antibiotics. Accordingly, targeted inhibition of the biosynthesis of petrobactin, a virulence-associated siderophore encoded by the asb locus in Bacillus anthracis, may hold promise as a potential therapy against anthrax. This study describes the biochemical characterization of AsbC, the first reported 3,4 dihydroxybenzoic acid-AMP ligase, and a key component in the biosynthesis of DHB spermidine (DHB-SP), the first isolable intermediate in petrobactin biosynthesis. AsbC catalyzes adenylation to the corresponding AMP ester of the unusual precursor 3,4-dihydroxybenzoate, in addition to benzoate substrates bearing hydrogen bond-donating substituents at the para and meta positions on the phenyl ring. In a second reaction, AsbC catalyzes transfer of the activated starter unit to AsbD, an aryl carrier protein similar to acyl and peptidyl carrier proteins that function in fatty acid, polyketide, and nonribosomal peptide biosynthesis. A third protein, AsbE, is shown to be responsible for condensation of 3,4 dihydroxybenzoyl-AsbD with spermidine, providing the DHB-spermidine arms that are linked to citrate for assembly of petrobactin. On the basis of the selective substrate profile of AsbC, a nonhydrolyzable analogue of 3,4-DHB-AMP was synthesized and shown to effectively inhibit AsbC function in vitro. PMID- 17346034 TI - Stabilization of G-quadruplex DNA and down-regulation of oncogene c-myc by quindoline derivatives. AB - Stabilization of G-quadruplex structures in the promoter region of certain oncogenes is an emerging field in anticancer drug design. Human c-myc gene is one of these oncogenes, and G-quadruplexes have been proven to be the transcriptional controller of this gene. In the present study, the interaction of quindoline derivatives with G-quadruplexes in c-myc was investigated. The experimental results indicated that these derivatives have the ability to induce/stabilize the G-quadruplexes in c-myc, which lead to down-regulation of the c-myc in the Hep G2 cell line. It was found that derivatives with terminal amino groups in their side chains would selectively bind to the isomers with the double nucleotide loops in the absence of K+. Molecular modeling studies revealed the binding mode between the derivatives and the G-quadruplexes is end-stacking at the 3'-position, and the positively charged side chain on the quindoline derivatives may contribute to the selectivity to certain loop isomers of topological quadruplexes as well as the improved stabilization action. PMID- 17346035 TI - Synthesis, critical micelle concentrations, and antimycobacterial properties of homologous, dendritic amphiphiles. Probing intrinsic activity and the "cutoff" effect. AB - Newkome-type, 1-->3 C-branched dendrons make an excellent headgroup for amphiphiles with ultralong, saturated, linear alkyl chains. Synthesis of a homologous series of five such amphiphiles from 14 to 22 carbons RNHCONHC(CH2CH2CO2H)3, R = n-CnH2n+1, n = 14, 16, 18, 20, 22-proceeds readily. These amphiphiles are soluble in aqueous solutions of triethanolamine. Surface tension measurements on this homologous series reveal an unusually gradual decrease in log critical micelle concentration (CMC) as the chain length increases. In fact, the tetradecyl homologue does not appear to form micelles. Further, measurements of minimal inhibitory concentration (MIC) by broth microdilution against Mycobacterium smegmatis as a function of the initial cell density provide a direct measure of the intrinsic activity (MIC0) of each homologue. The hexadecyl homologue is the most active at inhibiting growth with an MIC0 equal to 3.5 x 10-5 M, which is 100-fold below the CMC. PMID- 17346037 TI - Information content in organic molecules: Brownian processing at low levels. AB - The informatic properties of organic molecules have been the subject of our research during the past several years. In the present study, we investigate the lower levels wherein information is expressed via Brownian processing. Organic molecules are like other electronic devices in that their informatic details depend on the operating level in question. The low and high levels are distinguished (among other ways) by the amount of work they require for processing. In this work, a Brownian model is developed by which the low-level content of a chemical system can be quantified. The model is demonstrated for diverse organic molecules. In so doing, several scaling properties of low-level information are illustrated. In addition, the correspondence traits regarding the different levels are examined. Molecular information represents a capacity for work control such as during chemical reactions. Thus, the information expressed at low levels is examined in connection with the reaction pathway selectivity of organic compounds. PMID- 17346038 TI - On the cycle-dependence of topological resonance energy. AB - The topological resonance energy (TRE) was conceived in the 1970s. From the very beginning, it was known that TRE is equal to the collective energy-effect of all cycles present in a conjugated molecule. Also in the 1970s a theory of cyclic conjugation was elaborated, by means of which it was possible to compute the energy-effect ef(Z) of each individual cycle Z present in a conjugated molecule. Yet, the connection between TRE and the ef(Z)-values was, until now, not studied. We now show that TRE and the sum of the ef(Z)-values are closely correlated but that a certain correction needs to be made by taking into account the energy effects of pairs, triplets, quartets, etc. of cycles. PMID- 17346039 TI - Synthesis and voltammetry of [bmim]4[alpha-S2W18O62] and related compounds: rapid precipitation and dissolution of reduced surface films. AB - 1-n-Butyl-3-methylimidazolium (bmim) salts of [alpha-SiM12O40]4- and [alpha S2M18O62]4- (M = Mo, W) were synthesized and characterized. In sharp contrast to the multiple one-electron diffusion-controlled reduction processes expected in solution at a glassy carbon electrode, reduction of these salts beyond the one electron level in CH3CN (0.1 M [bmim][PF6]) led to rapid precipitation of arrays of microdroplets or microcrystals onto the surface. Upon oxidation these arrays dissolved on the electrochemical time scale, resulting in voltammograms displaying both diffusion-controlled and surface-confined behavior. These novel observations appear to be related to the ability of the [bmim]+ cations and polyoxometalate anions to form ion clusters in solution and to the lower solubilities of the reduced salts. PMID- 17346040 TI - Sulfur ligand substitution at the nickel(II) sites of cubane-type and cubanoid NiFe3S4 clusters relevant to the C-clusters of carbon monoxide dehydrogenase. AB - Substitution reactions at the nickel site of the cubane-type cluster [(Ph3P)NiFe3S4(LS3)]2- (2) have been investigated in the course of a synthetic approach to the C-clusters of CODH. Reaction of 2 with RS- or toluene-3,4 dithiolate affords [(RS)NiFe3S4(LS3)]3- (R = Et (5), H (6)) or [(tdt)NiFe3S4(LS3)]3- (7), demonstrating that anionic sulfur ligands can be bound at the NiII site. Clusters 5 and 6 contain tetrahedral Ni(micro3-S)3(SR) sites. Cluster 7 is of particular interest because it includes a cubanoid NiFe3(micro2 S)(micro3-S)3 core and an approximately planar Ni(tdt)(micro3-S)2 unit. The cubanoid structure is found in all C-clusters, and an NiS4-type unit has been reported in C. hydrogenoformans CODH. Clusters 5/6 are formulated to contain the core [NiFe3S4]1+ identical with Ni2+ (S = 1) + [Fe3S4]1- (S = 5/2) and 7 the core [NiFe3S4]2+ identical with Ni2+ (S = 0) + [Fe3S4]0 (S = 2) on the basis of structure, 57Fe isomer shifts, and 1H NMR isotropic shifts. Also reported are [(EtS)CuFe3S4(LS3)]3- (9) and [Fe4S4(LS3)(tdt)]3- (11). The structures of 5-7, 9, and 11 are presented. Cluster 11, with a five-coordinate Fe(tdt)(micro3-S)3 site, provides a clear structural contrast with 7, which is currently the closest approach to a C-cluster but lacks the exo iron atom found in the NiFe4S4,5 cores of the native clusters. (CODH = carbon monoxide dehydrogenase, LS3 = 1,3,5 tris((4,6-dimethyl-3-mercaptophenyl)thio)-2,4,6-tris(p-tolylthio)benzene(3-), tdt = toluene-3,4-dithiolate). PMID- 17346041 TI - Stabilization of acepentalene by coordination to transition metals: a DFT investigation. AB - The possibility of stabilizing the unstable acepentalene (acp) molecule through coordination to transition metals is investigated by means of DFT calculations. Comparison with related experimentally known pentalene complexes indicate that their acp homologues are just slightly less stable, suggesting that they could be synthesized and isolated. Other original mono- and trinuclear species, such as M(acp)2 (M = Zr, Hf), Co3(acp)2-, and Nb3(acp)2+, are also predicted to be stable. PMID- 17346042 TI - Quasi chiral phase separation in a two-dimensional orientationally disordered system: 6-nitrospiropyran on Au(111). AB - The adsorption and chiral expression of 6-nitrospiropyran (SP6) molecules on a Au(111) surface are studied by scanning tunneling microscopy (STM) in combination with density functional theory (DFT) calculations. Both the chirality and the adsorption orientation of each adsorbed SP6 molecule are determined. The racemic mixture of SP6 enantiomers forms two-dimensional (2D) domains with same close packed positional orders but different internal orientational structures due to the random distribution of two adsorption orientations in each domain. However, all these orientationally disordered 2D domains undergo spontaneous quasi chiral phase separation; the 2D SP6 domains separate into 1D homochiral chains in which the SP6 molecules adopt two orientations randomly. This novel phenomenon is attributed to the preferential formation of the energetic favorable configurations with both the C-H...O weak hydrogen bonds and the pi-stacking of the two moieties of each SP6 molecule. PMID- 17346043 TI - Atomic layer deposition of TiO2 from TiI4 and H2O onto SiO2 surfaces: ab initio calculations of the initial reaction mechanisms. AB - The initial surface reactions involved in the atomic layer deposition (ALD) of TiO2 from TiI4 and H2O onto a SiO2 substrate have been investigated using electronic structure calculations based on cluster models. The detailed atomic growth mechanisms on different types of functionalities on the SiO2 substrate have been proposed. The effects of quantum tunneling and hindered rotations of adsorbates on the rate of surface reactions have been investigated. The effects of tunneling were found to be negligible for all reactions, because typical ALD temperatures range from 150 to 450 degrees C. However, the rotational contributions to the rate constants must be taken into account in certain cases. All of the three surface functionalities investigated exhibit high chemical reactivity toward TiI4 precursors at typical ALD temperatures. The rate constants of the second half-reactions between Ti intermediates and H2O are 5-8 orders of magnitude smaller than the first half-reactions between TiI4 and the surface functionalities. Although the iodine release reaction has been used to explain previous experimental measurements, it is predicted to be unfavorable (kinetically and thermodynamically) and is unlikely to occur at typical ALD temperatures. Substitution of TiI4 with TiCl4 as the metal precursor can increase the binding energies of the absorbates onto the surface due to the high electronegativity of the Cl ligands. However, the activation barriers are not significantly different between these two metal precursors. More importantly, our calculations predict that TiI4 precursors tend to produce TiO2 films with fewer impurities than the TiCl4 precursors. PMID- 17346044 TI - Formation of helical mesopores in organic polymer matrices. PMID- 17346045 TI - Multi-oxygenase complexes of the gilvocarcin and jadomycin biosyntheses. PMID- 17346046 TI - Mechanistic studies of platinum(II)-catalyzed ethylene dimerization: determination of barriers to migratory insertion in diimine Pt(II) hydrido ethylene and ethyl ethylene intermediates. AB - The diimine platinum(II) ethylene hydride complex [(N/?N)Pt(H)(ethylene)][BAr'4] (1, N/?N = [(2,6-Me2C6H3)N=C(An)-C(An)=N(2,6-Me2C6H3)], An = 1,8-naphthalenediyl, Ar' = 3,5-(CF3)2C6H3) was prepared by protonation of the diethyl complex (N/?N)PtEt2 with [H(OEt2)2][BAr'4]. The energy barrier to interchange of the platinum hydride with the olefinic hydrogens in 1 was determined to be 19.2 kcal/mol by spin saturation transfer experiments. Complex 1 initiates ethylene dimerization; the ethyl ethylene complex (N/?N)Pt(Et)(ethylene)+ (2) has been identified as the catalyst resting state. Trapping of 1 by ethylene to yield 2 is a second-order process; kinetic studies suggest this occurs via trapping of a reversibly formed beta-agostic ethyl complex. Complex 2 has been isolated and characterized by X-ray crystallography. The barrier to migratory insertion of 2, the turnover-limiting step in catalysis, was determined to be 29.8 kcal/mol. The 1-butene hydride complex, (N/?N)Pt(H)(1-butene)+ (3), is a key intermediate in the dimerization cycle and has also been isolated and characterized. Surprisingly rapid rates of degenerate associative exchange of free ethylene with bound ethylene in complexes 1 and 2 as well as the rate of degenerate exchange of free nitrile with bound nitrile in (N/?N)Pt(Et)(CH3CN)+ are reported. PMID- 17346047 TI - Assembly of metallic carbon nanodots aligned on a vicinal Si(111)-7x7 surface. PMID- 17346048 TI - Structural and photophysical properties of adducts of [Ru(bipy)(CN)4]2- with different metal cations: metallochromism and its use in switching photoinduced energy transfer. AB - We show in this paper how the 3MLCT luminescence of [Ru(bipy)(CN)4]2-, which is known to be highly solvent-dependent, may be varied over a much wider range than can be achieved by solvent effects, by interaction of the externally directed cyanide ligands with additional metal cations both in the solid state and in solution. A series of crystallographic studies of [Ru(bipy)(CN)4]2- salts with different metal cations Mn+ (Li+, Na+, K+, mixed Li+/K+, Cs+, and Ba2+) shows how the cyanide/Mn+ interaction varies from the conventional "end-on" with the more Lewis-acidic cations (Li+, Ba2+) to the more unusual "side-on" interaction with the softer metal cations (K+, Cs+). The solid-state luminescence intensity and lifetime of these salts is highly dependent on the nature of the cation, with Cs+ affording the weakest luminescence and Ba2+ the strongest. A series of titrations of the more soluble derivative [Ru(tBu2bipy)(CN)4]2- in MeCN with a range of metal salts showed how the cyanide/Mn+ association results in a substantial blue shift of the 1MLCT absorptions, and 3MLCT energies, intensities, and lifetimes, with the complex varying from essentially non-luminescent in the absence of metal cation to showing strong (phi = 0.07), long-lived (1.4 micros), and high-energy (583 nm) luminescence in the presence of Ba2+. This modulation of the 3MLCT energy, over a range of about 6000 cm-1 depending on the added cation, could be used to reverse the direction of photoinduced energy transfer in a dyad containing covalently linked [Ru(bipy)3]2+ and [Ru(bipy)(CN)4]2- termini. In the absence of a metal cation, the [Ru(bipy)(CN)4]2- terminus has the lower 3MLCT energy and thereby quenches the [Ru(bipy)3]2+-based luminescence; in the presence of Ba2+ ions, the 3MLCT energy of the [Ru(bipy)(CN)4]2- terminus is raised above that of the [Ru(bipy)3]2+ terminus, resulting in energy transfer to and sensitized emission from the latter. PMID- 17346049 TI - Site-specific incorporation of allosteric-inhibition sites in a protein tyrosine phosphatase. PMID- 17346052 TI - Evidence for a plasma core during multibubble sonoluminescence in sulfuric acid. PMID- 17346053 TI - Regioselective ring-opening metathesis-cross metathesis of bridgehead-substituted 7-azanorbornene. AB - [structure: see text]. In this paper we describe a highly regioselective ring opening metathesis-cross metathesis (ROM-CM) process between methyl N-Boc-7 azabicyclo[2.2.1]hept-2-en-1-carboxylate, a bridgehead-substituted 7 azanorbornene system, and electron-poor olefins. The reaction opens the way to the synthesis of interesting alpha-amino diacids and pyrrolizinone derivatives that incorporate quaternary stereocenters. PMID- 17346054 TI - Diastereoselective self-assembly of double-stranded helicates from Troger's base derivatives. AB - [structure: see text]. Several ligands based on the rigid, V-shaped structure of Troger's base bearing 2,2'-bipyridine and 2-pyridylmethanimine moieties have been synthesized. These ligands undergo diastereoselective self-assembly to dinuclear double-stranded D2d-symmetric helicates upon coordination to copper(I) and silver(I) ions as elucidated by NMR techniques and ESI mass spectrometric methods. PMID- 17346055 TI - A new molecular scaffold for the formation of supramolecular peptide double helices: the crystallographic insight. AB - [structure: see text]. A series of water-soluble synthetic dipeptides (1-3) with an N-terminally located beta-alanine residue, beta-alanyl-l-valine (1), beta alanyl-l-isoleucine (2), and beta-alanyl-l-phenylalanine (3), form hydrogen bonded supramolecular double helices with a pitch length of 1 nm, whereas the C terminally positioned beta-alanine containing dipeptide (4), l-phenylalanyl-beta alanine, does not form a supramolecular double helical structure. beta-Ala-Xaa (Xaa = Val/Ile/Phe) can be regarded as a new motif for the formation of supramolecular double helical structures in the solid state. PMID- 17346056 TI - Remarkably mild and efficient intramolecular Friedel-Crafts cyclization catalyzed by In(III). AB - [structure: see text]. Indium(III) salts were found to be highly effective catalysts for the intramolecular Friedel-Crafts reaction of simple allylic bromides and arenes. In(III) salts appear to be the most general and possess unique halophilic properties as a Lewis acid for this reaction among the catalysts evaluated to date. Deactivated arenes possessing chloride, bromide, and fluoride underwent smooth reaction when activated by InCl3. PMID- 17346057 TI - The first 5,6-dihydroxyindole tetramer by oxidation of 5,5',6,6'-tetrahydroxy- 2,4'-biindolyl and an unexpected issue of positional reactivity en route to eumelanin-related polymers. AB - [structure: see text]. The first tetramer of the eumelanin precursor 5,6 dihydroxyindole has been obtained, as the acetyl derivative, by peroxidase/H2O2 induced oxidative coupling of 5,5',6,6'-tetrahydroxy-2,4'-biindolyl (2) in the presence of Zn2+ ions. The tetramer, 5,5',5'',5''',6,6',6'',6'''-octaacetoxy 2,4':2',3'':2'',4'''-tetraindolyl (acetylated 7), incorporates an unprecedented 2,3'-biindolyl substructure suggestive of a different positional reactivity of the 5,6-dihydroxyindole system when framed into a dimeric scaffold. PMID- 17346058 TI - Highly convergent route to cyclopeptide alkaloids: total synthesis of ziziphine N. AB - [structure: see text]. A highly convergent protocol to cyclopeptide alkaloids, as demonstrated by the first total synthesis of antiplasmodial agent ziziphine N, is developed. The key elements include construction of its aryl ether unit via Mitsunobu reaction, installation of its enamide part via CuI/N,N-dimethylglycine catalyzed coupling reaction, and ring closure with coupling agents such as FDDP and DPPA. PMID- 17346059 TI - Organocatalytic asymmetric Friedel-Crafts alkylation of indoles with simple alpha,beta-unsaturated ketones. AB - [structure: see text]. The first general and highly enantioselective organocatalytic Friedel-Crafts alkylation of indoles with simple alpha,beta unsaturated ketones has been accomplished. Central to these studies has been the identification of a new catalyst amine salt, in which both the cation and the anion are chiral, that exhibits high reactivity and selectivity for iminium ion catalysis. PMID- 17346060 TI - An efficient waste-free oxidative coupling via regioselective C-H bond cleavage: Rh/Cu-catalyzed reaction of benzoic acids with alkynes and acrylates under air. AB - [structure: see text]. The direct oxidative coupling of benzoic acids with internal alkynes proceeds efficiently in the presence of a rhodium/copper catalyst system under air to afford the corresponding isocoumarin derivatives. The reaction forms no wastes except for water. Under similar conditions, the aerobic coupling with acrylates also takes place smoothly to produce 7 vinylphthalide derivatives via divinylation and subsequent cyclization. PMID- 17346061 TI - Stereocontrolled glycoside and glycosyl ester synthesis. neighboring group participation and hydrogenolysis of 3-(2'-benzyloxyphenyl)-3,3 dimethylpropanoates. AB - [reaction: see text] The 2-O-[3-(2'-benzyloxyphenyl)-3,3-dimethylpropanoate] and 2-O-[3-(2'-benzyloxy-4',6'-dimethylphenyl)-3,3-dimethylpropanoate] esters enable the synthesis of a range of beta-glucosides and alpha-mannosides through neighboring participation in excellent yield, and are removed by hydrogenolysis in concert with the cleavage of benzyl esters in the presence of other esters making them particularly well suited to the stereocontrolled synthesis of glycosyl esters. PMID- 17346062 TI - Sampling strategies and variability in fruit pulp micronutrient contents of west and central african bananas and plantains (Musa species). AB - The variability in fruit micronutrient contents in a selection of Central and West African Musa varieties cultivated under standardized field conditions was studied. Analysis of the within-fruit, within-hand, and within-plant as well as the between-plant variations demonstrated that both provitamin A carotenoids (pVACs) and mineral micronutrient (Fe, Zn) contents vary significantly across all sample groups. The variations in pVACs contents appear to be at least partly related to differences in the developmental status of the fruit, but the observed trends were genotype-specific. The mean pVACs concentrations per genotype indicated that there is substantial genetic variation in the fruit pVACs contents between Musa cultivars, with orange-fleshed plantain varieties (AAB) having generally higher fruit pVACs contents than dessert bananas (AAA). It was not possible to identify consistent trends between the sampling position and fruit Fe/Zn contents. Once the within-bunch micronutrient variability has been accounted for, the mean variations in fruit micronutrient contents between individual plants of a variety generally fell to within acceptable limits. Results are discussed within the framework of standardizing sampling and developing strategies to screen for the nutritional values of new and existing Musa varieties. PMID- 17346063 TI - pH-Activated fusogenic transmembrane LV-peptides. AB - LV-peptides mimic the in vitro fusogenicity of synthetic fusion protein transmembrane domains. The original versions of these peptides consist of a variable hydrophobic core (containing leucine and/or valine residues (LV)) that is flanked by invariant lysine triplets at both termini. Previously, peptide fusogenicity was correlated with the structural plasticity of their hydrophobic cores. Here, we examined the functional importance of positively charged flanking residues. To this end, we determined the fusogenicities of peptide variants that contain terminal His and/or Lys triplets. Interestingly, liposome fusion by peptides with His triplets was triggered by acidic pH. The pH dependence of fusion is reflected by a sigmoidal titration curve whose midpoint is close to the pKa value of histidine. Thus, only peptides with positively charged residues at both termini are fusogenic. The previously established dependence of fusogenicity on the sequence of the hydrophobic peptide core of Lys-flanked LV-peptides was preserved with the His-flanked versions at low pH. We propose that the structural flexibility of the core region as well as positive terminal charges are required for LV-peptide function in lipid mixing. In a potential practical application, the pH-dependent LV-peptides might prove to be useful in the lipofection of eukaryotic cells. PMID- 17346064 TI - Investigation of the effects of the local environment on the surface-enhanced Raman spectra of striped gold/silver nanorod arrays. AB - The effects of the local environment on surface-enhanced Raman scattering (SERS) spectra utilizing gold, silver, and gold/silver striped nanorod array substrates was investigated. The arrays were fabricated using an electrochemical metal deposition into an anodic aluminum oxide template. The analyte chosen for this study was p-nitroso-N,N-dimethylaniline (p-NDMA), which has an electronic structure that is highly sensitive to its surrounding environment. Changes in the peak positions and peak ratios were used to probe the influence of water and the striping pattern on the SERS signal of p-NDMA. We present the results of the fabrication and characterization of the nanorod array substrates, as well as SERS spectra of p-NDMA in both polar and nonpolar environments and SERS spectra on a variety of striped nanorod arrays. The Raman data suggests that the p-NDMA molecule exists in a more polarized state when bound to the gold as compared to the silver rods. We have attempted to use these differences to determine whether the SERS signal predominantly arises from the tips of the rods or from the interior of the array. PMID- 17346065 TI - Controlling interfacial curvature in nanoporous silica films formed by evaporation-induced self-assembly from nonionic surfactants. I. Evolution of nanoscale structures in coating solutions. AB - The double-gyroid phase of nanoporous silica films formed by evaporation-induced self-assembly (EISA) has been shown to possess facile mass-transport properties and may be used as a robust template for the nanofabrication of metal and semiconductor nanostructures. Recently, we developed a new synthesis of double gyroid nanoporous silica films where the aging time of the coating solution prior to EISA was the key parameter required to control the interfacial curvature that results upon self-assembly of the film. Here, we use 29Si nuclear magnetic resonance (NMR) and small-angle X-ray scattering (SAXS) to investigate the nanoscale structure of the coating solutions used to obtain double-gyroid nanoporous silica films. NMR and SAXS were carried out on the water, ethanol, silica, and poly(ethylene oxide)-b-poly(propylene oxide)-b-alkyl (EO17-PO12-C14) surfactant coating solutions as well as similar solutions that excluded either the silica or the surfactant. NMR data reveal that the silica monomers in the coating solution condense very rapidly to form rings and connected ring species. After 1 day of aging, all monomers and dimers have disappeared, and the distribution is dominated by Q2 and Q3 species, where the superscript in Qn describes the number of silicon atoms in the second coordination shell of the central silicon. Over the course of the next 9 days, the Q3 population slowly rises at the expense of the Q2 and Q3t populations. Absolute intensity SAXS measurements reveal that the size of the silica clusters increases steadily during this aging period, reaching an average radius of gyration of 9.0 A after 9 days of aging. Longer aging results in the continued growth of clusters with a mass fractal dimension of 1.8. Absolute intensity SAXS data also reveals that micelles are not present in the coating solution. At 9% volume fraction of surfactant, the coating solution is far above the aqueous critical micellar concentration. However, even a small amount of ethanol inhibits micellization. SAXS data also shows that when surfactant is present the radius of gyration is larger but increases more slowly. This indicates that there are weak associative interactions between the silica clusters and surfactant in solution that reduce the cluster-cluster growth rate. In part II of this work, we use the results discovered here to interpret the effects of aging on interfacial curvature in the nanostructured films that self-assemble from these solutions. PMID- 17346066 TI - Controlling interfacial curvature in nanoporous silica films formed by evaporation-induced self-assembly from nonionic surfactants. II. Effect of processing parameters on film structure. AB - The double-gyroid phase of nanoporous silica films has been shown to possess facile mass-transport properties and may be used as a mold to fabricate a variety of highly ordered inverse double-gyroid metal and semiconductor films. This phase exists only over a very small region of the binary phase diagram for most surfactants, and it has been very difficult to synthesize metal oxide films with this structure by evaporation-induced self-assembly (EISA). Here, we show the interplay of the key parameters needed to synthesize these structures reproducibly and show that the interfacial curvature may be systematically controlled. Grazing angle of incidence small-angle X-ray scattering (GISAXS) is used to determine the structure and orientation of nanostructured silica films formed by EISA from dilute silica/(poly(ethylene oxide)-b-poly(propylene oxide)-b alkyl) surfactant solutions. Four different highly ordered film structures are observed by changing only the concentration of the surfactant, the relative humidity during dip-coating, and the aging time of the solution prior to coating. The highly ordered films progress from rhombohedral (Rm) to 2D rectangular (c2m) to double-gyroid (distorted Iad) to lamellar systematically as interfacial curvature decreases. Under all experimental conditions investigated, increasing the aging time of the coating solution was found to decrease the interfacial curvature. In particular, this parameter was critical to being able to synthesize highly ordered, pure-phase double-gyroid films. The key role of the aging time is shown via processing diagrams that map out the interplay between the aging time, composition, and relative humidity. 29Si nuclear magnetic resonance (NMR) spectroscopy and solution-phase small-angle X-ray scattering (SAXS) of the aged coating solutions presented in part I of this series are then used to interpret the effects of aging prior to dip-coating. Specifically, it was found that a predictive model based on volume fractions and the silica cluster stoichiometry obtained from 29Si NMR qualitatively explains the trends observed with composition and aging. However, apart from the effects of relative humidity, a quantitative comparison of the predicted phase with the experimental processing diagram suggests that less-condensed silica clusters are more effective at swelling the EO blocks at early aging times. This enhanced swelling decreases with aging time and results in lower-curvature nanostructures such as the double gyroid. The decrease in swelling is attributed to the decreased thermodynamic driving force for the more-condensed silica clusters to mix with the EO block of the surfactant. PMID- 17346067 TI - Surface characterizations of spin-coated films of ethylcellulose and hydroxypropyl methylcellulose blends. AB - Films of pure ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) polymers and EC/HPMC blends were prepared from solutions by spin coating where isopropyl alcohol (IPA), water, and IPA/water cosolvent were used as solvents. Surface structures of the films were investigated using optical microscopy, atomic force microscopy (AFM), and Raman mapping and spectroscopy. For the films prepared from EC/HPMC blend solutions using the IPA/water cosolvent, different domain structures such as islands or pits and phase separation between EC and HPMC were observed by optical microscopy and AFM. The nature of the polymer components on the surface of the films was identified by Raman mapping and spectroscopy. Experimental results also indicated that polymer composition, solvent, and temperature during spin coating had significant impacts on surface structures of the films. PMID- 17346068 TI - Underpotential deposition of thallium, lead, and cadmium at silver electrodes modified with self-assembled monolayers of (3-mercaptopropyl)trimethoxysilane. AB - Investigation of the underpotential deposition (UPD) of three metals-Tl, Pb, and Cd-on Ag surfaces modified with self-assembled monolayers (SAMs) of (3 mercaptopropyl)trimethoxysilane (3MPT) is reported. On the basis of the observation of negative potential shifts for their UPD processes, Tl and Pb undergo UPD directly on the underlying Ag surface by insertion between the Ag-S bond. This process is proposed to occur by penetration of the 3MPT monolayer by hydrated metal ions through spaces in six-membered siloxane rings that form at the terminus of the 3MPT layer after hydrolysis and condensation. In contrast, Cd does not undergo similarly facile UPD at 3MPT-modified Ag electrodes due to a hydrated ion size too large to fit through these openings. The voltammetric evidence that suggests that the hydrated metal cation size, as described by the Stokes diameter, is the primary determinant of Ag electrode accessibility for UPD through the cross-linked 3MPT layer is further supported by molecular mechanics energy minimization computations of six-membered siloxane rings on each of the three low-index faces of Ag. Finally, the 3MPT monolayer is shown to be exceptionally stable to repeated UPD/stripping cycles of Tl and Pb in contrast to SAMs of similar thickness formed from normal alkanethiols. PMID- 17346069 TI - Surface adsorption and micelle formation of surface active ionic liquids in aqueous solution. AB - Aqueous solutions of three kinds of surface active ionic liquids composed of the 1-alkyl-3-methylimidazolium cation have been investigated by means of surface tension and electrical conductivity measurements at room temperature (298 K). The surface tension measurements provided a series of parameters, including critical micelle concentration (cmc), surface tension at the cmc (gammacmc), adsorption efficiency (pC20), and effectiveness of surface tension reduction (Picmc). In addition, with application of the Gibbs adsorption isotherm, maximum surface excess concentration (Gammamax) and minimum surface area/molecule (Amin) at the air-water interface were estimated. The effect of sodium halides, NaCl, NaBr, and NaI, on the surface activity was also investigated. It was found that both the pC20 and the Picmc were rather larger than those reported for traditional ionic surfactants and the cmc values were somewhat lower than those for typical cationic surfactants, alkyltrimethylammonium bromides, and comparable to typical anionic surfactants, sodium alkyl sulfates. These results demonstrate that the surface activity of long-chained imidazolium IL is somewhat superior to that of conventional ionic surfactants. PMID- 17346070 TI - Substrate- and time-dependent photoluminescence of quantum dots inside the ultrathin polymer LbL film. AB - The photoluminescence of CdSe/ZnS quantum dots (QDs) in different configurations at solid surfaces (glass, silicon, PDMS, and metals) is considered for three types of organization: QDs directly adsorbed on solid surfaces, separated from the solid surface by a nanoscale polymer film with different thickness, and encapsulated into a polymer film. The complete suppression of photoluminescence for QDs on conductive metal surfaces (copper, gold) indicated a strong quenching effect. The temporal variation of the photoluminescent intensity on other substrates (glass, silicon, and PDMS) can be tuned by placing the nanoscale (3-50 nm) LbL polymer film between QDs and the substrate. The photooxidation and photobleaching processes of QD nanoparticles in the vicinity of the solid surface can be tuned by proper selection of the substrate and the dielectric nanoscale polymer film placed between the substrate and QDs. Moreover, the encapsulation of QD nanoparticles into the polymer film resulted in a dramatic initial increase in the photoemission intensity due to the accelerated photooxidation process. The phenomenon of enhanced photoemission of QDs encapsulated into the ultrathin polymer film provides not only the opportunity for making flexible, ultrathin, QD containing polymer films, transferable to any microfabricated substrate, but also improved light emitting properties. PMID- 17346071 TI - Altered proteome in Burkholderia pseudomallei rpoE operon knockout mutant: insights into mechanisms of rpoE operon in stress tolerance, survival, and virulence. AB - We have previously shown that the alternative sigma factor sigmaE (RpoE), encoded by rpoE, is involved in stress tolerance and survival of Burkholderia pseudomallei. However, its molecular and pathogenic mechanisms remain unclear. In the present study, we applied gel-based, differential proteomics to compare the cellular proteome of an rpoE operon knockout mutant (RpoE Mut) to that of wild type (K96243 WT) B. pseudomallei. Quantitative intensity analysis (n = 5 gels from 5 individual culture flasks in each group) revealed significantly differential expression of 52 proteins, which were subsequently identified by Q TOF MS/MS. These included oxidative, osmotic, and other stress response proteins; chaperones; transcriptional/translational regulators; metabolic enzymes; proteins involved in cell wall synthesis, fatty synthesis, glycogen synthesis, and storage; exported proteins; secreted proteins; adhesion molecule; protease/peptidase; protease inhibitor; signaling proteins; and other miscellaneous proteins. The down-regulation of several stress response proteins, chaperones, transcriptional/translational regulators, and proteins involved in cell wall synthesis in RpoE Mut provided some new insights into the mechanisms of the rpoE operon for the stress tolerance and survival of B. pseudomallei. In addition, the proteomic data and in vivo study indicated that the rpoE operon is also involved in the virulence of B. pseudomallei. Our findings underscore the usefulness of proteomics for unraveling pathogenic mechanisms of diseases at the molecular level. PMID- 17346072 TI - Polyelectrolyte microstructure in chitosan aqueous and alcohol solutions. AB - This work deals with chain ordering in aqueous and water-alcohol solutions of chitosan. The so-called polyelectrolyte peak is investigated by small-angle synchrotron X-ray scattering. The polyelectrolyte microstructure was characterized by the position of the maximum of the polyelectrolyte scattering peak qmax, which scales with the polymer concentration cp as qmax approximately cp alpha. An evolution of the power law exponent alpha is observed as a function of the degree of acetylation (DA) of chitosan, which is responsible for changes of both the charge density (f) and the hydrophobicity of the polymer chains. The results highlighted the two organization regimes of the theory of Dobrynin and Rubinstein, investigated here for the first time for a natural polymer. At low DAs, alpha approximately 1/2, in agreement with a pearl necklace organization where the structure is controlled by the string between pearls. For higher DA, alpha approximately 1/3, and the correlation revealed by the polyelectrolyte peak is controlled by the pearls. This analysis offers a way to study quantitatively the balance between solvophobic-solvophilic interactions that play an important role in the solution properties of natural polymers. In addition, the role of several parameters acting on the interaction balance were evidenced, such as the nature of the counterion, the composition of the solvent (amount of alcohol in the aqueous solution), and the screening of Coulombic forces by salt addition. Finally, the nanostructure transition from a polyelectrolyte solution to a physical gel is discussed. The gel state is reached when the solvophobic interactions are favored, but depending on the gelation route the polyelectrolyte ordering could be preserved or not. PMID- 17346073 TI - Cytotoxic alkylpiperidine alkaloids from the Brazilian marine sponge Pachychalina alcaloidifera. AB - Four bis-piperidine alkaloids, madangamine F (1), haliclonacyclamine F (2). and arenosclerins D (3) and E (4), have been isolated from the marine sponge Pachychalina alcaloidifera and have been identified by analysis of spectroscopic data. The alkaloids displayed cytotoxic activity against different cancer cell lines. These results support the hypothesis of a common biogenetic origin for the Haplosclerida bis-piperidine and bis-pyridine alkaloids. PMID- 17346074 TI - Coniothyrione, a chlorocyclopentandienylbenzopyrone as a bacterial protein synthesis inhibitor discovered by antisense technology. AB - Bacterial protein synthesis inhibitors interact mainly with rRNA and to some extent ribosomal proteins, which are potential targets for developing new antibacterial agents. Specifically, the ribosomal protein S4 of the 30s ribosomal subunit known as ribosomal protein small-subunit D (rpsD) may be useful as a target. The antisense-rpsD gene-sensitized two-plate assay led to the discovery of a novel chlorinated cyclopentandienylbenzopyrone antibiotic, coniothyrione, C14H9ClO6, isolated from Coniothyrium cerealis MF7209. It exhibited liquid MICs of 16-32 microg/mL against Staphylococcus aureus, Bacillus subtilis, Haemophilus influenzae, Streptococcus pneumoniae, and Enterococcus faecalis and >64 microg/mL against Escherichia coli. Isolation, structure elucidation, and antibacterial activity of coniothyrione are described. PMID- 17346075 TI - Pycnanthuquinone C, an unusual 6,6,5-tricyclic Geranyltoluquinone from the Western Australian brown alga Cystophora harveyi. AB - Chemical investigation of the Western Australian marine brown alga Cystophora harveyi resulted in the isolation of the new linearly fused 6,6,5-tricyclic compound pycnanthuquinone C (1), in addition to four previously reported geranyltoluquinol derivatives. Structures were elucidated by interpretation of spectrometric data. Compounds with the same cyclic skeleton as 1 have been reported to be useful drug leads for the treatment of type 2 diabetes, while compounds 4 and 7 are known constituents of Chinese medicinal herbs. A biosynthetic scheme encompassing all of the geranyltoluquinol derivatives isolated from C. harveyi is proposed. PMID- 17346076 TI - Triterpenoids from the floral spikes of Betula platyphylla var. japonica and their reversing activity against multidrug-resistant cancer cells. AB - Four new triterpenes, together with 16 known triterpenes, were isolated from the floral spikes of Betula platyphylla var. japonica in a search for compounds capable of reversing multidrug resistance in cancer cells. The structures of the new triterpenes were elucidated as 3,4-seco-olean-4(23),13(18)-dien-3-oic acid (1), 3,4-seco-urs-4(23),20(30)-dien-3-oic acid (2), 3-O-methylmalonylepiocotillol II (6), and 3-O-methylmalonylcabraleahydroxylactone (16) by spectroscopic examination. The cytotoxicity of the isolated triterpenes against human cancer cell lines as well as multidrug-resistant cancer cell lines was evaluated. Most of the isolated triterpenes showed very weak cellular toxicities. Although no discernible differences were found in the cytotoxicities for the tested compounds against sensitive and resistant cell lines, the cytotoxicities for several triterpenes against multidrug-resistant cancer cell lines (KB-C2 or K562/Adr) were enhanced in the presence of nontoxic concentrations of colchicine or doxorubicin. Compound 10 reversed the cytotoxicity of colchicine against KB-C2 cells at 8.1 microM and showed comparable potency to 5 microM verapamil. PMID- 17346077 TI - Extending the record of meroditerpenes from Cacospongia marine sponges. AB - A new meroditerpene, (+)-isojaspic acid (1), along with two known meroditerpenes, cacospongin D (2) and jaspaquinol (3), have been isolated from a marine sponge Cacospongia. Comprehensive taxonomic identification distinguished this Cacospongia apart from morphologically similar Psammocinia. The absolute stereochemistry of 1 was elucidated on the basis of extensive 1D and 2D NMR techniques and analysis of the optical rotation versus (+)-zonarol (8), (+) isozonarol (9), (-)-dactylosponol (10), and (+)-hyatellaquinone (11). Furthermore, bioactivity evaluation showed that the meroditerpenes isolated significantly inhibited Staphylococcus epidermidis. PMID- 17346078 TI - Antineoplastic agents. 550. Synthesis of 10b(s)-epipancratistatin from (+) narciclasine. AB - By means of a five-step reaction sequence, narciclasine (2a), isolated from Narcissus sp., was converted to 10b(S)-epipancratistatin (3a) in 5.7% overall yield. The key step entailed a radical-initiated 10b,1 C-O cleavage employing tributyltin hydride to yield a B/C cis ring juncture (3b). Biological evaluation of 10b(S)-epipancratistatin (3a) provided evidence that antineoplastic activity was reduced by a factor of 10 when the B/C trans juncture was replaced with a B/C cis ring juncture. PMID- 17346079 TI - Synthesis of valiolamine and some precursors for bioactive carbaglycosylamines from (-)-vibo-quercitol produced by biogenesis of myo-inositol. AB - A convenient and practical synthesis of valiolamine (4) and its related carbaglycosylamine glycosidase inhibitors from (-)-vibo-quercitol (13), a compound readily produced by biogenesis of myo-inositol (9), is described. PMID- 17346080 TI - Total synthesis and correct absolute configuration of malyngamide U. AB - The enantioselective synthesis of the previously proposed structure of malyngamide U (1) was accomplished in 18 steps from (S)-(+)-carvone. The key steps involved a hydroxymethylation of (S)-(+)-carvone and an asymmetric Henry reaction of aldehyde (+)-5, as well as condensation with the acid 3. The 1H and 13C NMR data of the synthetic compound 1 were not consistent with the data of the reported malyngamide U. The C-2' epimer of compound 1 was therefore synthesized by a similar reaction sequence. While the NMR data of C-2' epimer 23 were in full agreement with those of the reported product, the discrepancy in the specific rotation data suggested the correct structure of malyngamide U should be structure 2, in which the absolute configuration of the amine part was enantiomeric with that in compound 23. Then the correct absolute configuration of revised malyngamide U (2) was confirmed by the similar synthesis from (R)-(-) carvone. PMID- 17346081 TI - Compared behavior of 5-deoxy-5-iodo-D-xylo- and L-arabinofuranosides in the reductive elimination reaction: a strong dependence on structural parameters and on the presence of Zn2+. A combined experimental and theoretical investigation. AB - In the framework of a project devoted to the chemical transformation of monosaccharides from hemicelluloses into higher added value materials, the zinc induced reductive elimination from 5-deoxy-5-iodo derivatives of D-xylose and L arabinose was carried out. This study gave us the opportunity to observe surprising behaviors. In particular, the reaction strongly depends on structural parameters (protecting group pattern, configuration at C-4) and on the presence of Zn2+ ions. Collaterally with the experimental work, water solvent PCM HF-DFT (MPW1K/LANL2DZ) computations were performed to obtain insight into the mechanism for the reductive part of the reaction sequence. Without Zn2+, the zinc insertion reaction was found to proceed through a concerted but non-synchronous process involving a relatively large energy barrier (32 kcal mol-1) that directly leads to the presumed organozinc intermediate. In the presence of Zn2+, a three-step mechanism was identified in which the cation coordinates the anomeric and ring oxygen atoms and also the sugar iodine atom, causing an activating effect on the zinc insertion process by facilitating the homolytic rupture of the C-I bond. Complexes between zinc and Zn2+ bound carbohydrates were characterized with large stabilization energies, suggesting that Zn2+ might enhance the affinity of the organic compound with the zinc metal surface. PMID- 17346082 TI - A simple method for measuring long-range 1H-13C coupling constants in organic molecules. AB - This study presents a simple method for measuring long-range heteronuclear coupling constants between protons and proton-bearing carbons. The approach involves recording two conventional 1D-TOCSY experiments in which the offset of the selective proton pulse is set on the low- and high-frequency 13C satellites of an isolated proton signal, Hi. Long-range heteronuclear coupling values between the 13Ci bonded to Hi and the protons Hj,k...n that belong to the same spin system were easily determined from the relative displacement of the relayed Hj,k...n signals in the satellite-selective TOCSY spectra. The sense of the displacement indicated the sign of the coupling constants. PMID- 17346083 TI - Expedient synthesis of substituted (diphenylphosphinoylmethyl)benzenes. AB - An efficient protocol for the synthesis of structurally diverse (diphenylphosphinoylmethyl)benzenes is described. The reaction employs readily available carboxylic acids, chlorodiphenylphosphine, and water as the reagents. A 97% reduction in the reaction times and substantially higher yields of products result, up to a 60% increase, if the reactions are performed under microwave irradiation. The first examples of transition-metal-catalyzed reactions applied to 4-bromo-1,3-bis(diphenylphosphinoylmethyl)benzene are also reported. PMID- 17346084 TI - Cross-Diels-Alder reactions of 6-oxo-1-sulfonyl-1,6-dihydropyridine-3 carboxylates. AB - Electron-poor 6-oxo-1-sulfonyl-1,6-dihydropyridine-3-carboxylates 1b-d undergo cross-Diels-Alder reactions with electron-rich dienes 4a-f under hyperbaric conditions, reacting either as dienophiles to yield normal-electron-demand (NED) cycloadducts 10 and/or 11 or as dienes to give inverse-electron-demand (IED) cycloadducts 12 and/or 13. The latter are converted into 14 and/or 15 through an NED cycloaddition with a second equivalent of electron-rich diene. Acyclic dienes display a propensity to yield NED products, whereas cyclic dienes tend to favor IED cycloadducts. High-pressure activation compares favorably with thermal or microwave activation in terms of both yields and suppression of the transformation of 1 into unreactive pyridines 3. Whereas the Cope rearrangement from IED to NED occurs under thermal conditions, no evidence of its involvement under high pressure could be detected. These and other data point to similar activation energies for the NED and IED processes under these conditions. PMID- 17346085 TI - Synthesis of upper-rim allyl- and p-methoxyphenylazocalix[4]arenes and their efficiencies in chromogenic sensing of Hg2+ ion. AB - A series of upper-rim p-allyl and p-methoxyphenylazocalix[4]arenes (6, 8, 9a,b, and 10a,b) were synthesized and shown to exhibit substantial color changes upon complexation with Hg2+ ion. Both the upper-rim p-allyl- and p-methoxyphenylazo groups on calix[4]arenes are proven to be key components in the recognition of Hg2+ ion. Job's plots revealed 1:1 binding stoichiometry for all these p-allyl- and p-arylazo-coupled calix[4]arenes with Hg2+ ions and Benesi-Hilderbrand plots were used for determination of their association constants. Our results also demonstrated that two p-methoxyphenylazo groups prefer to bind Hg2+ in a distal orientation rather than a proximal one, and if there are three p-methoxyphenylazo groups, the third flanking p-methoxyphenylazo group plays a role in disturbing the binding of the two distal diazo groups. Furthermore, it should be noted that triazocalix[4]arenes (6, 9a, and 9b) responded to all 14 metal ions without showing much preference among the eight transition-metal ions screened in this work (Cr3+, Ni2+, Cu2+, Ag+, Cd2+, Hg+, Hg2+, and Pb2+). PMID- 17346086 TI - Assessing the suitability of 1,2,3-triazole linkers for covalent immobilization of chiral ligands: application to enantioselective phenylation of aldehydes. AB - Alkynyl-functionalized amino alcohols have been covalently supported on azidomethylpolystyrene resins with different levels of functionalization through Cu(I)-catalyzed 1,3-dipolar cycloadditions ("click chemistry"). The resulting 1,2,3-triazole-substituted resins, characterized by different levels of ligand loading and, depending on the nature of the alkynyl-functionalized amino alcohol, the presence of a one-carbon, four-carbon, or eight-carbon linear spacer, have been tested as catalysts in the enantioselective phenyl transfer from zinc to aldehydes. High catalytic activities and enantioselectivities (up to 82% ee) have been recorded. The influence of structural characteristics of the resin on enantioselectivity are discussed, and the limitations in enantiocontrol inherent to the use of a 1,2,3-triazole linker have been rationalized with the help of DFT calculations on model systems. PMID- 17346087 TI - A reductive cyclization approach to attenol A. AB - A reductive cyclization strategy was applied to the synthesis of attenol A. This nontraditional approach to the spiroacetal structure illustrated several advantages of the reductive cyclization methodology. The attenol A core was formed in a carbon-carbon bond coupling that gave rise to a previously inaccessible spiroacetal epimer, a new method to synthesize thioketene acetals from a phenyl sulfone was realized, and the configurational stability of a nonanomeric spiroacetal was evaluated. A minor byproduct in the reductive cyclization reaction was identified that for the first time allowed direct evaluation of the stereoselectivity in a reductive cyclization of a dialkyloxy alkyllithium reagent. PMID- 17346088 TI - Polyhydroxylated indolines and oxindoles from C-glycosides via sequential Henry reaction, Michael addition, and reductive amination/amidation. AB - 6-nitro-2'-carbonyl-C-glycofuranosides synthesized via Henry reaction from 1-C allyl 5-aldo-C-glycoside underwent an intramolecular Michael addition to afford nitrocyclohexanol derivatives in good to excellent yield. Reduction of the nitro group followed by intramolecular amination with ketone and aldehyde and amidation with ester produced indoline and oxindole derivatives, respectively, in excellent yield. PMID- 17346089 TI - The first asymmetric total syntheses and determination of absolute configurations of xestodecalactones B and C. AB - The first efficient asymmetric total syntheses of xestodecalactones B and C have been accomplished in 10 steps with an overall yield of 22 and 20.2%, respectively. The key steps involve the utility of Evans oxazolidinone-mediated syn-aldol condensations to establish the C-9 configuration and the macrolide ring formation by intramolecular acylation. The absolute configurations of xestodecalactones B and C have been determined via these syntheses. PMID- 17346090 TI - Random-telegraph-signal noise and device variability in ballistic nanotube transistors. AB - In field-effect transistors (FETs), charge trapping in the gate oxide is known to cause low-frequency noise and threshold shifts. Here we calculate the effect of single trapped charges in a carbon nanotube FET, using the nonequilibrium Greens function method in a tight-binding approximation. We find that a single charge can shift and even rescale the entire transfer characteristic of the device. This can explain both the large "random telegraph signal" noise and the large variations between nominally identical devices. We examine the dependence on both the thickness and dielectric constant of the gate dielectric, suggesting routes to reduce electrical noise. PMID- 17346091 TI - Voltage regulation of fluorescence emission of single dyes bound to gold nanoparticles. AB - An organic dye, SAMSA, bound to gold nanoparticles, displays random photoactivated fluorescence blinking whose rate depends on the size of the nanoparticles. We report experiments indicating that (1) the dye emission wavelength is red-shifted (10-30 nm) by applying an external low voltage (1-10 V) and that (2) the fluorescence emission of single dyes can be resonantly driven by tuning the alternating external bias frequency from 1 to 3 Hz, depending on the nanoparticle size. These properties appear highly valuable and promising for devising light emitting nanostructures. PMID- 17346093 TI - Approach to AF in older adults on target. PMID- 17346094 TI - Appropriate use of NSAIDs: considering cardiovascular risk in the elderly. AB - In the first of this two-part article, we reviewed essential gastrointestinal (GI) data necessary for choosing selective COX-2 inhibitors (coxibs) versus nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), as well as other NSAID-related GI issues. Although GI considerations are critical to appropriate NSAID selection, the worldwide withdrawal of rofecoxib because of adverse cardiovascular (CV) events has changed the focus of appropriate NSAID selection. In part 2, we discuss relevant CV adverse effects related to NSAID use. Based upon data reviewed, we believe there are differences between coxibs and that all NSAIDs, including nonselective agents, have some degree of CV risk. Their use should be based upon patient's risks and benefits. Our clinical use pathway or algorithm will continue to frame the ongoing discussion and guide clinicians along what has become a difficult decision in daily practice. PMID- 17346095 TI - Confronting atrial fibrillation in the elderly: stroke risk stratification and emerging antithrombotic therapies. AB - As many as one in four patients over age 40 will develop atrial fibrillation (AF), a significant risk factor for stroke. Although most clinicians are aware of the benefits of antithrombotic therapy, especially warfarin, for prevention of stroke, current guidelines for selection of antithrombotic therapy are confusing and inconsistently applied. The CHADS2 risk-stratification scheme, based on a clinical history of heart failure, hypertension, age >75, diabetes, or prior stroke, is a useful clinical tool to identify patients likely to benefit from warfarin, distinguishing these patients from patients at lower risk for whom aspirin is sufficient. Risk factors for intracerebral hemorrhage include anticoagulation intensity, hypertension, age, and previous stroke or cerebrovascular disease. Cerebral amyloid angiopathy and leukoaraiosis identified by high-resolution brain imaging are under investigation, but better schemes for stratifying bleeding risk are needed. In the future, new anticoagulants that are safer and easier to administer than warfarin will improve the benefit/risk burden for elderly patients with AF. PMID- 17346096 TI - Skin ulceration on a burn scar. PMID- 17346097 TI - Long-Term toxicity studies in Canine of E10A, an adenoviral vector for human endostatin gene. AB - E10A, a recombinant adenovirus type 5 vector carrying the human endostatin gene, may be a promising gene therapy drug in the treatment of solid tumors by antiangiogenesis, but a preclinical safety evaluation of E10A has not yet been performed. With high and low doses equivalent to 30 and 7.5 times the human curative dose, respectively, intramuscular injections of E10A were given once daily, 6 days/week, for 3 months, followed by a 1-month recovery period. As of 4 months, all experimental animals appeared generally healthy: normal behavior and eating habits, no nausea, vomiting, or salivation, no abnormal changes in urination or defecation, and increased body weight with the time of experiment. Urinalysis, hemogram, blood biochemistry, electrocardiogram, macroscopic and microscopic studies of organs and tissues were done before treatment, at month 3 of treatment, and 1 month posttreatment. At all time points, no significant abnormal toxic effects were noted. Preliminary investigation of E10A immunotoxicity in dogs indicated that anti-adenoviral antibodies were generated, in a dose- and time-independent manner, after E10A injection. Our data demonstrated that, long term, high-dose intramuscular administration of recombinant human endostatin-carrying adenovirus (E10A) was not notably toxic and might be safe for clinical therapeutic use, although additional long-term toxicity studies by other administration routes are still necessary. PMID- 17346099 TI - Differential effects of EGF and TGF-beta1 on fibroblast activity in fibrin-based tissue equivalents. AB - Transforming growth factor-beta1 (TGF-beta1) is commonly used to promote matrix production for engineered tissues in vitro, yet it also enhances fibroblast contractility. For applications where contraction is undesirable, we hypothesized that epidermal growth factor (EGF) would yield equivalent mechanical properties without enhancing contractility. In this study, the response of human dermal fibroblasts to EGF (5 ng/mL) and TGF-beta1 (5 ng/mL) was determined within hemispheric fibrin-based gels by assessing matrix compaction and strength, cell number, collagen production, and contractility. After 3 weeks, both cytokines enhanced compaction relative to controls, and EGF roughly doubled matrix strength over controls and TGF-beta1-treated samples. TGF-beta1 induced alpha-smooth muscle actin (alphaSMA) expression whereas EGF did not. TGF-beta1 also increased retraction following substrate release while EGF reduced retraction. Treatment with cytochalasin D revealed that, regardless of growth factor, approximately 10% of the total retraction was due to residual matrix stress accumulated during cell mediated remodeling. EGF increased the cell number by 17%, whereas TGF-beta1 decreased the cell number by 63% relative to controls. EGF and TGF-beta1 stimulated greater collagen content than controls by 49% and 33%, respectively. These data suggest that EGF may be an attractive alternative to TGF-beta1 for engineering fibrin-based connective tissue substitutes with adequate strength and minimal tissue contractility. PMID- 17346100 TI - Reengineering salivary gland cells to enhance protein secretion for use in developing artificial salivary gland device. AB - Salivary glands (SGs) are considered exocrine glands, which mainly secrete water into the oral cavity. Nevertheless, they also exhibit a smaller endocrine secretory pathway toward the bloodstream. The concept of an artificial SG device for exocrine fluid secretion into the oral region in xerostomic patients has been previously studied. The purpose of the current study was to examine the potential of such a device for enhancing bioactive protein secretion. We engineered a plasmid encoding a SG-specific signal peptide sequence adjacent to a normally nonsecreted encoded reporter gene creating a chimera protein, and examined if this construct can enhance secretion from salivary epithelial cells. An N terminal encoding epidermal growth factor (EGF) sequence was synthesized and inserted into a pGL3 control vector 5' of a firefly luciferase gene, creating a pGL3-EGF signal peptide (pGL3-EGFSP) fused vector. This vector was cotransfected with a pRL-CMV vector containing a Renilla luciferase gene, in 293 cells (serving as controls), and human submandibular gland ductal epithelial (HSG), rat submandibular gland acinar epithelial (SMIE), and rat submandibular gland ductal epithelial (A5) salivary cell lines. The transfected 293, SMIE, and HSG cells showed 8-, 18-, and 40-fold higher luciferase activity, respectively. These observations lead to the concept of an envisioned secretory device, which can serve as a potential biological pump for bioactive proteins. PMID- 17346102 TI - Oncolytic virus therapy--foreword. AB - We are very pleased and proud to be able to publish this special issue of Current Cancer Drug Targets devoted to oncolytic virus therapy covering basic and clinical research on adenovirus, vaccinia virus, herpes virus, and Newcastle disease virus. In these papers, we welcome the world's top authorities in the field who have generously contributed their latest review articles for exclusive publication in this special issue. Moreover, this issue also includes a range of opinion from government drug organizations. Here we simply wish to bring together the newest knowledge and experience in the field of cutting-edge oncolytic virus therapy for researchers and every kind of cancer therapist. The Foreword presents a historical perspective on the development of oncolytic virus together with the encouraging results of recent clinical trials (e.g., H101 has been tested in clinical trial of nearly 250 patients and approved for human use by the Chinese FDA, while PV701 has been tried in over 110 patients, as described in our special issue). PMID- 17346103 TI - Oncolytic viruses: what's next? AB - Cancer is a complex disease that often eludes successful treatment due to its propensity to evolve or adapt in the face of current therapeutic regimes. It is reasonable to suggest that sophisticated therapeutics that can attack cancers in multiple, but targeted ways, will be necessary in order to improve current success rates. It is the thesis of this article that Oncolytic Viruses (OVs), are a new generation of "smart therapeutics" for cancer with tremendous potential to revolutionize the management of what has become one of mankind's scourges. A number of viruses are being developed around the world for this purpose (one has already been approved for human use in China [1]) and I propose that it is now essential to embrace the technology and use our recent and evolving understanding of the molecular biology of cancer to fully exploit the oncolytic virus platform. In the remainder of this article I speculate on some of the next important steps in OV development and directions the platform may be headed in the future. PMID- 17346104 TI - From ONYX-015 to armed vaccinia viruses: the education and evolution of oncolytic virus development. AB - The current field of oncolytic virus development has evolved from, and been educated by, the route adenoviruses have taken to Phase III development in the United States (Onyx-015) and commercial approval in China (H101). Clinical development of these E1B-deleted viruses showed that a staged approach, from single-agent intratumoral injections to trials testing intravenous delivery and trials in combination with approved therapies is judicious and can be successful. Additional oncolytic products are in development, including andenovirus plus other promising platforms such as herpes simplex virus, Newcastle disease virus, reovirus and vaccinia virus. These second-generation products seek to expand clinical utility beyond the modest local efficacy of Onyx-015/H101 to potent systemic delivery and efficacy. Improvement of efficacy in metastatic cancer will depend not only on enhanced killing of tumor cells, but also on achieving intravenous delivery and better intratumoral dissemination. Many viruses inherently replicate preferentially in tumors, and engineering can increase this therapeutic index by targeting genetic features of cancers. However, both viruses and cancer cells have complex biologies. Therefore, research may reveal that there is not a single predictive factor for tumor specificity. For example, the Onyx-015 mechanism-of-selectivity has proved to be complex. Further research regarding pathway dependence for other oncolytic viruses may also reveal multiple influences on their tumor tropism. PMID- 17346105 TI - Clinical trials with oncolytic adenovirus in China. AB - Since the 1990s, oncolytic viruses were utilized to treat cancer patients from phase I to phase III. Oncolytic virus development in China has been keeping in step with that in other countries and even accelerated the process in some fields, especially in conducting clinical trials. H101 is one kind of oncolytic adenovirus with E1B-55KD and partial E3 deleted developed by Shanghai Sunwaybio. From 2000-2004, phase I to phase III clinical trials for treating head and neck cancer were conducted in China. Clinical data show that H101 is well tolerable and has good efficacy when combined with chemotherapy in some cancer treatment modalities. We review the clinical results and relative issues of H101 in treating cancer and discuss approaches and possible improvements for the future. Information on other oncolytic viruses developing in China is also provided. PMID- 17346106 TI - Oncolytic herpes simplex virus type 1 and host immune responses. AB - The use of oncolytic herpes simplex virus type 1 (HSV-1) is a promising strategy for cancer treatment. Accumulating evidence indicates that, aside from the extent of replication capability within the tumor, the efficacy of an oncolytic HSV-1 depends on the extent of induction of host antitumor immune responses. Ways to modify the host immune responses toward viral oncolysis include expression of immunostimulatory molecules using oncolytic HSV-1 as a vector and co administration of reagents that modulate immune reactions. Viral propagation may be enhanced via temporary suppression of innate immune responses. Elucidation of the role of the host immune system in oncolytic HSV-1 therapy is the key to establishing the approach as a useful clinical means for cancer treatment. PMID- 17346107 TI - Phase 1 clinical experience using intravenous administration of PV701, an oncolytic Newcastle disease virus. AB - PV701 is a naturally-attenuated, non-recombinant, oncolytic strain of Newcastle disease virus that displays preclinical intravenous (IV) efficacy. PV701 is selective at killing human cancer cells versus normal human cells based on tumor specific defects in the interferon (IFN)-mediated antiviral response. This oncolytic virus displays a broad spectrum of antitumor activity in vitro and in vivo. Preclinical models successfully predicted key clinical parameters including the mechanism of toxicity, two complementary strategies (desensitization and slow infusion) to reduce toxicity, and the starting dose for phase 1 trials. In three phase 1 trials of 114 patients using IV administration of PV701, Wellstat Biologics Corporation has evaluated the effects of dose, schedule, and infusion rate for PV701. Three general classes of side effects were seen: flu-like symptoms; tumor-site-specific adverse events (AEs); and infusion reactions. The first PV701 dose desensitized the patient to the side effects of further doses, allowing a marked increase in the maximum tolerated dose for subsequent doses compared to the first dose. Tumor responses were first noted at the higher doses achieved using desensitization. In the most recent phase 1 trial of 19 patients at Hamilton, Ontario, that employed desensitization, high repeat doses, and a slower infusion rate (Hamilton Regimen), there were six responses (4 major; 2 minor) and a total of six patients with survival for at least 2 years. In addition, patient tolerability improved using the Hamilton Regimen compared to IV bolus dosing used previously. Phase 2 studies of this novel biologic agent are about to begin. PMID- 17346108 TI - Clinical experiment of mutant herpes simplex virus HF10 therapy for cancer. AB - We reviewed our clinical trial using mutant herpes simplex virus "HF10". We have evaluated the safety and effect of HF10 against recurrent breast cancer since 2003 and also applied HF10 to non-resectable pancreatic cancer since 2005. An oncolytic herpes simplex virus type 1, mutant HF10, has been isolated and evaluated for anti-tumor efficacy in syngeneic immunocompetent mouse models. From long time before clinical trial, we have found that the mutant virus can have remarkable potential to effectively treat cancer in experimental studies using animals, and that all of the surviving mice acquire resistance to rechallenge of the tumor cells. A number of studies have shown that HF10 is effective and safe for use in localized or peritoneally disseminated malignant tumors of non neuronal origin in animals. Pilot studies using HF10 have been initiated in patients with metastatic breast cancer. For each patient, 0.5 ml HF10 diluents at various doses were injected into test nodule, and 0.5 ml sterile saline was injected into a second nodule. All patients were monitored for local and systemic adverse effects, and the nodules were excised 14 days after viral injection for histopathological studies. All patients tolerated the clinical trial well. While no adverse effects occurred, there was cancer cell death and 30-100% regression histopathologically in recurrent breast cancer. As mentioned above, intratumoral injection of mutant herpes simplex virus HF10 for recurrent metastatic breast cancer was safe and effective. Also a trial for non-resectable pancreatic cancer being carried out on the basis of the above result has proved to be innocuous and has been in progress to assess the clinical benefit and enhance the potentiality of HF10 against cancer. PMID- 17346109 TI - HSV-1 viral oncolysis and molecular imaging with PET. AB - Viral oncolysis, the destruction of cancer cells by replicating viruses, is a new modality of cancer therapy. This strategy involves use of viruses that are either genetically engineered to replicate preferentially in neoplastic cells, or use of viruses that display innate tropism for neoplastic cells. These viruses may also be modified to deliver transgenes to destroy cancer cells. While numerous viruses may be used for this form of cancer therapy, HSV-1 is an attractive vector for viral oncolysis due to several characteristics including its high infectivity, ease of genetic engineering, large transgene capacity, and the availability of an effective medical treatment for Herpes simplex virus infections. The HSV-1 viral genome has been manipulated to generate replication conditional viruses which target cancer cells. Although these viruses are programmed to replicate preferentially in cancer cells, there is some unintended replication in normal cells. Currently, biopsy is the gold standard for monitoring the therapeutic effects of viral oncolysis. However, a non-invasive test capable of serial monitoring of therapy during the treatment period is required for both preclinical and clinical studies. Positron emission tomography (PET) using HSV thymidine kinase as the PET reporter gene offers the desired qualities of a non invasive test which can be easily repeated to determine the location and magnitude of viral replication and tumor lysis. We review viral oncolysis, focusing on HSV-1 viral oncolysis and therapeutic monitoring by PET. PMID- 17346110 TI - Oncolytic viruses driven by tumor-specific promoters. AB - Oncolytic viruses can selectively replicate in and lead to tumor cell lysis with minimal infection/replication potential in adjoining non-neoplastic tissue. Because of paramount safety concerns, first-generation oncolytic viruses were designed to be significantly attenuated in their lytic potential. Results from recent clinical trials have revealed the safety of this approach, but have underscored the urgency for design and testing of more tumor-selective and potent viruses to realize the full therapeutic potential of this revolutionary treatment modality. With the discovery of various molecular/genetic changes associated with neoplasia, tumor-specific transcriptional targeting of viral virulence is being tapped to generate tumor- and tissue-specific variants. This review will focus on the various strategies exploited to generate viruses whose virulence is governed by tumor-specific transcriptional events. PMID- 17346111 TI - Telomerase-specific oncolytic virotherapy for human cancer with the hTERT promoter. AB - Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus mediated lysis of tumor cells after selective viral propagation within the tumor. For targeting cancer cells, there is a need for tissue- or cell-specific promoters that can express in diverse tumor types and are silent in normal cells. Recent advances in molecular biology have fostered remarkable insights into the molecular basis of neoplasm. Telomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site (IRES). Telomelysin replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human cells lacking telomerase activity. Thus, the hTERT promoter confers competence for selective replication of Telomelysin in human cancer cells, an outcome that has important implications for the treatment of human cancers. This article reviews recent findings in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the hTERT promoter. PMID- 17346112 TI - Regulatory aspects of oncolytic virus products. AB - Many types of oncolytic viruses, wild-type virus, attenuated viruses and genetically-modified viruses, have been developed as an innovative cancer therapy. The strategies, nature, and technologies of oncolytic virus products are different from the conventional gene therapy products or cancer therapy products. From the regulatory aspects to ensure the safety, efficacy and quality of oncolytic viruses, there are several major points during the development, manufacturing, characterization, non-clinical study and clinical study of oncolytic viruses. The major issues include 1) virus design (wild-type, attenuated, and genetically engineered strains), 2) poof of concept in development of oncolytic virus products, 3) selectivity of oncolytic virus replication and targeting to cancer cells, 4) relevant animal models in non clinical studies, 5) clinical safety, 6) evaluation of virus shedding. Until now, the accumulation of the information about oncolytic viruses is not enough, it may require the unique approach to ensure the safety and the development of new technology to characterize oncolytic viruses. PMID- 17346115 TI - Reproducibility and scalability of solvent-free microwave-assisted reactions: from domestic ovens to controllable parallel applications. AB - The heating of different parallel arrays in domestic ovens offers the possibility to perform multiple reactions in one irradiation experiment, blending the advantages of microwave heating technology and parallel chemistry. However, they are usually performed without an appropriate temperature control; thus, reproducibility becomes a major issue limiting the application of such reactions. This is exemplified when working at a different scales or using different instruments. For the first time a typical solvent-free reaction described in a domestic oven has been reproduced in monomode reactor, scaled up in a controlled multimode oven and reproduced in parallel, 24 reactions were carried out in a well plate. Parallel reactions were performed in a Weflon multiwell plate to assure identical conditions for each individual reaction. As many reactions under microwave irradiation have been performed in solvent-free conditions, this result opens new possibilities in reproducibility, scalability and combinatorial chemistry and permits to take advantage of many synthetic procedures described in domestic ovens. PMID- 17346116 TI - Selection of new chromogenic substrates of serine proteinases using combinatorial chemistry methods. AB - Chemical synthesis, physicochemical characterization and kinetic investigations of a tetrapeptide library of chromogenic substrates containing the amide of 5 amino-2-nitrobenzoic acid (Anb(5,2)-NH(2)) at their C-termini are reported. Anb(5,2)-NH(2) served as a chromophore released upon enzymatic action. The library consisting of 9567 peptides was synthesized using the portioning-mixing method and was screened against bovine a-chymotrypsin and human leukocyte elastase in solution applying an iterative approach. The selected chromogenic substrates were resynthesized and further modified at their N- and C-termini. Finally, two sequences, Z-Phe-Ala-Thr-Tyr-Anb(5,2)-NH(2) and Z-Phe-Phe-Pro-Val Anb(5,2)-NH(2), were obtained as highly specific substrates for bovine alpha chymotrypsin and human leukocyte elastase, respectively. The method of synthesis and selection of chromogenic substrates of serine proteinases described herein is straightforward and can be applied to design substrates for other proteases. PMID- 17346117 TI - Homogenous time resolved fluorescence assay to identify modulators of cap dependent translation initiation. AB - Eukaryotic initiation factor (eIF) 4F plays a key role in recruiting 40S ribosomes and associated factors to mRNA templates during translation initiation. The function of this heterotrimeric complex is to deliver an RNA helicase to the 5' cap proximal region of mRNAs in preparation for ribosome binding. To study the interaction between subunits of this complex, as well as identify small molecules that could interfere with their association, we developed a time resolved fluorescence assay that allows monitoring of interactions between two subunits of eIF4F. We have performed a small molecule chemical screen of >73,000 compounds using this assay. PMID- 17346118 TI - Target specific compound identification using a support vector machine. AB - In many cases at the beginning of an HTS-campaign, some information about active molecules is already available. Often known active compounds (such as substrate analogues, natural products, inhibitors of a related protein or ligands published by a pharmaceutical company) are identified in low-throughput validation studies of the biochemical target. In this study we evaluate the effectiveness of a support vector machine applied for those compounds and used to classify a collection with unknown activity. This approach was aimed at reducing the number of compounds to be tested against the given target. Our method predicts the biological activity of chemical compounds based on only the atom pairs (AP) two dimensional topological descriptors. The supervised support vector machine (SVM) method herein is trained on compounds from the MDL drug data report (MDDR) known to be active for specific protein target. For detailed analysis, five different biological targets were selected including cyclooxygenase-2, dihydrofolate reductase, thrombin, HIV-reverse transcriptase and antagonists of the estrogen receptor. The accuracy of compound identification was estimated using the recall and precision values. The sensitivities for all protein targets exceeded 80% and the classification performance reached 100% for selected targets. In another application of the method, we addressed the absence of an initial set of active compounds for a selected protein target at the beginning of an HTS-campaign. In such a case, virtual high-throughput screening (vHTS) is usually applied by using a flexible docking procedure. However, the vHTS experiment typically contains a large percentage of false positives that should be verified by costly and time consuming experimental follow-up assays. The subsequent use of our machine learning method was found to improve the speed (since the docking procedure was not required for all compounds from the database) and also the accuracy of the HTS hit lists (the enrichment factor). PMID- 17346119 TI - Directed evolution of oxygenases: screening systems, success stories and challenges. AB - The field of directed evolution of oxygenases (mono-, di- and epoxygenases) is rapidly advancing as an increasing number of success stories indicate. A significant number of screening systems have been developed to specifically improve oxygenase properties. Oxygenases will become very valuable biocatalysts for synthetic applications in industry when stability, cofactor and activity properties match industrial demands. This review summarizes screening systems and principles of screening systems that have been used for directed evolution of oxygenases. Sections on mutagenic conditions, mutant library size and property improvements provide a comprehensive picture on performance and limitations of current directed evolution methodologies for oxygenases. A discussion of challenges in the directed evolution of oxygenases for industrial exploitation concludes this review. PMID- 17346120 TI - Fluorous-enhanced multicomponent reactions for making drug-like library scaffolds. AB - Multicomponent reactions (MCRs) generate multiple bonds in a single reaction process, which is highly efficient to construct relatively complex molecules. Conducting post-MCR modification reactions further increases the molecular complexity and diversity. MCR has become a powerful approach to make drug-like molecules in lead generation chemistry. In fluorous MCR (F-MCR), one of the starting materials is attached to a fluorous tag and used as the limiting agent. After the MCR, the fluorous component is fished out from the reaction mixture and used for post-MCR modifications. The fluorous tag can be finally removed in traceless fashion by displacement or cyclization reactions. Unique fluorous technology such as fluorous solid-phase extraction (F-SPE) facilitates the separation process. Other techniques such as microwave irradiation and plate-to plate SPE can also be used to make the F-MCR even more efficient. Syntheses of unique heterocyclic and natural product-like library scaffolds using Ugi/de Boc/cyclization, MCR/Suzuki coupling, and [3+2] cycloaddition/de-tag/cyclization protocols are described in this paper. PMID- 17346121 TI - Analysis of similarity/dissimilarity of long DNA sequences based on three 2DD curves. AB - Some 2D graphical representations of DNA sequences have been reported by several authors, which give visual characterizations of DNA sequences. In this paper, we present a new 2D graphical representation of DNA sequences without degeneracy. Furthermore, we propose two methods for the visualization and analysis of long DNA sequences. PMID- 17346122 TI - Medial vascular calcification in diabetes mellitus and chronic kidney disease: the role of inflammation. AB - Medial vascular calcification in an increasingly recognized problem in patients with diabetes and patients with chronic kidney disease. Calcification of the media is associated with significant morbidity and mortality. The phenotypic and the molecular fingerprints of medial calcification in patients with diabetes and patients with chronic kidney disease are strikingly similar. While disturbances in divalent ion homeostasis have been proposed to play a role in calcification of the media in patients with chronic kidney disease, patients with diabetes have an apparently intact bone and mineral metabolism. Chronic kidney disease as well as diabetes are now recognized as pro-inflammatory states. This review will explore the pathobiology of medial vascular calcification, review the evidence for diabetes and chronic kidney disease as pro-inflammatory states, and discuss the role of inflammation as a mechanistic link that explains the similarities in phenotypic and molecular characteristics of medial calcification in patients with chronic kidney disease and patients with diabetes mellitus. PMID- 17346123 TI - Statins in the prevention of cardiovascular events in patients with renal failure. AB - HMG-CoA reductase inhibitors (statins) are among the most widely used hypolypemizing drugs with a pleiotropic activity. Numerous clinical trials have demonstrated that statins can have a significant effect in the prevention of cardiovascular diseases in the general population. In patients with renal failure, this drug preserves the hypolypemizing efficacy found in the general population without increasing their unwanted side-effects. The re-analysis of data from epidemiological studies conducted on the general population has confirmed that statins provide cardiovascular protection also in subjects with renal failure. These data have been partly confirmed by the findings made by 4D (Die Deutsche Diabetes Dialyse Studie) and Alert studies, conducted on diabetic patients on dialysis and patients with renal transplants, respectively. The results of other studies, such as AURORA, SHARP, REnal and Vascular End stage Disease, and ESPLANADE, clearly indicate that statins prevent cardiovascular disease in patients with renal insufficiency, just as they do in the general population. PMID- 17346124 TI - The role of coronary angioplasty in the management of patients with stable coronary artery disease. AB - A review of the existing evidence on the impact of percutaneous coronary intervention (PCI) in the setting of stable coronary artery disease (CAD) indicates that in patients with chronic coronary artery disease and good left ventricular function, PCI does not confer any clear benefit in terms of hard long term clinical outcomes, such as mortality, myocardial infarction or the need for subsequent revascularization, as compared with medical conservative treatment. By comparing the benefits against cost considerations, it seems that many percutaneous interventions that are currently performed in patients with non acute CAD are probably not justified. Determination of the functional significance of coronary artery disease can often be a challenge. Conventional coronary angiography and imaging tests, although suitable for risk stratification, may not be satisfactory as independent guides for specific decision-making regarding the optimum management of these patients. The development of more efficient methods for the identification of coronary lesions that should be the target of coronary intervention is certainly needed. PMID- 17346125 TI - Potential therapeutic targets in cirrhotic cardiomyopathy. AB - Cirrhotic cardiomyopathy is a recently identified pathological condition defined as "a chronic cardiac dysfunction in patients with cirrhosis characterized by blunted contractile responsiveness to stress and/or altered diastolic relaxation with electrophysiological abnormalities, in the absence of known cardiac disease". Overall there seems to be a link between the progression of liver function impairment, the development of portal hypertension and the degree of hyperdynamic circulation, the hallmark of the deranged cardiovascular function in advanced liver diseases. Although mechanical factors contribute to much of the increased resistance within the liver in portal hypertension, there is clearly a vasculogenic component to the development, perpetuation and progression of this syndrome as well. The vascular component of portal hypertension includes an increase in splanchnic blood flow, as well as an increase in intrahepatic vascular resistance. Dysregulation of the nitric oxide system appears to play a key role in both these processes with a paradoxical reduction of intrahepatic availability despite increased disposal in the splanchnic and other vascular districts with adverse effects on cardiac function and structure. Nevertheless, other putative mediators of cardiac damage in cirrhosis have been proposed and their role in the pathogenesis of cirrhotic cardiomyopathy investigated. This review involves a discussion of data achieved on pathogenesis and clinical features of cirrhotic cardiomyopathy but mainly focuses on considerations on potential therapeutic targets, in the light of the evidence that this mainly subclinical condition merges to clinical relevance when challenged with those therapeutic interventions and procedures currently employed to treat the major complications of cirrhosis that might produce a negative impact on the cardiovascular system. PMID- 17346126 TI - The role of catecholamines in formation and resolution of pulmonary oedema. AB - Pulmonary oedema (PO) can emerge from mechanical disorders in pulmonary circulation leading to elevated fluid filtration in the lung, or from increased vascular permeability due to inflammatory or toxic injury of the alveolar capillary barrier. A number of these disorders causing PO is associated with increased catecholamine (CA) levels in plasma and lung tissue and/or increased sympathetic activation such as neurogenic PO, high-altitude PO or PO in patients with phaeochromocytoma. Experimental CA stimulation in animals induced PO after less than one hour of infusion. Both alpha- and beta-adrenergic mechanisms are involved in the pathogenesis but also in the resolution of PO. CAs increase pulmonary capillary pressure and thus, enhance fluid filtration into the pulmonary interstitium. Additionally, by activation of proinflammatory cytokines, they induce pulmonary inflammation that may lead to capillary leak. Finally, they play an important role in the regulation of alveolar fluid clearance. The present paper considers the pathways by which CAs contribute to the development of PO of various origin. PMID- 17346127 TI - Neural control of blood pressure: focusing on capsaicin-sensitive sensory nerves. AB - Hypertension is a major risk factor leading to devastating cardiovascular events such as myocardial infarction, stroke, heart failure, and renal failure. Despite intensive research in this area, mechanisms underlying essential hypertension remain to be defined. Accumulating evidence indicates that neural components including both sympathetic and sensory nerves innervating the cardiovascular and renal tissues play a key role in regulating water and sodium homeostasis and blood pressure, and that abnormalities in these nervous systems contribute to increased salt sensitivity and development of hypertension. In contrast to relatively well-defined sympathetic nervous system, the role of sensory nerves in the control of cardiovascular homeostasis is largely unknown. Data from our laboratory show that degeneration of capsaicin-sensitive sensory nerves renders a rat salt sensitive in terms of blood pressure regulation. Evidence is also available indicating that sensory nerves, in interacting with other neurohormonal systems including the sympathetic nervous system, the renin-angiotensin aldosterone system, the endothelin system, and superoxide, regulate cardiovascular and renal function in such that they play a counter-balancing role in preventing salt-induced increases in blood pressure under pathophysiological conditions. Altered activity of the sensory nervous system, a condition existed in both genetic and experimental models of hypertension, contributes to the development of hypertension. This article focuses on reviewing the current knowledge regarding the possible role of sensory nerves in regulating blood pressure homeostasis as well as the function and regulation of novel molecules expressed in sensory nerves. PMID- 17346128 TI - Discovery of new cardiovascular hormones for the treatment of congestive heart failure. AB - In 1628, Harvey first correctly described the heart as a pump. It was another 350 years before the heart was established as an endocrine gland that synthesized a family of peptide hormones that regulate blood volume and blood pressure. There are now five peptide hormones made in the heart which have been demonstrated to have beneficial effects in persons with congestive heart failure. One of these peptide hormones i.e. brain natriuretic peptide (BNP) is commercially available and has been widely used in the United States for the treatment of acute congestive heart failure under the name Nesiritide/Natrecor. Nesiritide has one serious side effect, i.e. it may worsen renal function in persons with acute decompensated cardiac failure. The best of these peptide hormones for the treatment of chronic heart failure is a cardiac hormone named vessel dilator which enhances sodium and water excretion 4- to 5-fold in persons with congestive heart failure but vessel dilator's biologic effects lasts six hours compared to less than 30 minutes for BNP, without the deleterious effects of BNP on renal function. This review will focus on six cardiac hormones' discovery, identification and comparison of their beneficial effects and side effects in humans with congestive heart failure. PMID- 17346129 TI - Orthostatic hypotension: evaluation and treatment. AB - Orthostatic hypotension (OH) may be dependent upon various neurogenic and non neurogenic disorders and conditions. Neurogenic causes include the main autonomic failure syndromes, primary (multiple system atrophy, pure autonomic failure, and autonomic failure associated with Parkinson's disease) and secondary (central nervous system diseases, peripheral neuropathies and systemic diseases). Non neurogenic causes of OH include cardiac impairment, fluid and electrolyte loss, vasodilatation, and old age. A number of drugs may also cause OH, through their vasoactive action or by interfering with the autonomic nervous system. Symptoms of OH are debilitating, often confining patients to bed, and longitudinal studies have shown that OH increases the risk of stroke, myocardial ischemia and mortality. The therapeutic goal is to decrease the incidence and severity of postural symptoms, rather than restore normotension. In non-neurogenic OH, treatment of the underlying cause may be curative. In neurogenic OH a combination of non-pharmacological and pharmacological measures is often needed. Patient education and non-pharmacological measures represent the first step; among these interventions, fluid repletion and physical countermanoeuvres have been proven very effective. Pharmacological treatment comprises a number of agents acting on blood vessels, on blood volume or with other pressor mechanisms. The drugs most currently used are fludrocortisone and midodrine. Fludrocortisone expands the extravascular body fluid volume and improves alpha-adrenergic sensitivity. Midodrine is a peripheral, selective alpha1-adrenergic agonist that causes arterial and venous vasoconstriction. Despite the wide use of these drugs, multicentre, randomised and controlled studies for the treatment of OH are still scarce and limited to few agents and groups of patients. Pharmacological management of OH substantially improves the quality of life of patients, although it may be problematic. The development of supine hypertension and subsequent congestive heart failure should be avoided, especially in those patients with a pre-existing cardiovascular risk, such as in diabetes or ischemic heart disease. PMID- 17346130 TI - Peptides derived from platelet non-integrin collagen-receptors or types I and III collagen inhibit collagen-platelet interaction. AB - Platelet-collagen interaction plays an important role in hemostasis and pathological thrombosis. Upon an injury to the subendothelium of a blood vessel wall, platelets adhere to the denuded substrate, aggregate, and release biological substances. Many investigators have explored the use of blocking agents to interrupt the final step of binding fibrinogen on glycoprotein (GP) IIb/IIIa of activated platelets. A potent peptide is Arg-Gly-Asp-Ser (RGDS) and its derivatives in various forms. Results from many clinical trials show that the efficacy of these antagonists does not lie in blocking the adhesion of platelets to the distal site(s) of the injury as expected. Because type I and type III collagens are predominant components of blood vessel walls, other laboratories and ours have defined various active peptides from either collagen molecules or platelets as useful for blocking collagen-platelet interaction. An active hybrid peptide derived from both platelet types I and type III collagen receptors that abolishes type I and type III collagen-induced platelet aggregation has been obtained. The hybrid peptide inhibits the binding of type I and type III collagens to washed human platelets, platelet aggregation, and the adhesion of washed platelets to rabbit aortic segments. However, the usefulness of the defined hybrid peptide in preventing thrombi formation in vivo requires further investigation. PMID- 17346131 TI - Disease progression in children with vertically-acquired HIV infection in sub Saharan Africa: reviewing the need for HIV treatment. AB - Approximately 700,000 children become newly infected with HIV annually, mainly through mother-to-child transmission (MTCT), making paediatric HIV a leading cause of morbidity and mortality worldwide. The substantial interest in preventing MTCT (PMTCT) has generated information on rates of transmission and associated factors, but there is a lack of information on disease progression and mortality in vertically-infected children, especially from resource-poor settings. Peer-review journals with titles or abstracts containing reference to the review's themes were selected using widely available search engines. We review relevant literature on mortality in children born to HIV infected mothers; morbidity and mortality associated with paediatric HIV infections; eligibility to and efficacy of antiretroviral therapy (ART). Child mortality is independently associated with maternal HIV status and maternal death, with paediatric infection resulting in approximately 4 fold increase in mortality by age 2 years. Morbidities seen in infected children were similar to those seen in uninfected children, although the rates and recurrences of illness were greater. There is some evidence that progression to AIDS may be more rapid in resource poor settings, although data on this are very limited. PMTCT and paediatric ART have been shown to be highly successful in resource-limited settings, but are not universally applied. Further efforts to increase coverage of both PMTCT and paediatric ART could substantially reduce the numbers of children becoming infected and improve survival of those infected. Additionally, improvements in health infrastructures could improve care provision, not only through improved detection and monitoring but also through treatment of co-morbidities and nutritional support. PMID- 17346132 TI - What strategies to boost production of affordable fixed-dose anti-retroviral drug combinations for children in the developing world? AB - BACKGROUND: No more than 8% of HIV positive children needing treatment in low- and middle-income countries have access to antiretroviral drugs (ARVs). Children presently account for about 4% of all treated patients, while for equitable access they should make up at least 13%. AIMS: This study explores key issues, implications and interaction dynamics to boost production of easy-to-use and affordable fixed-dose combination (FDC) ARVs for children in the developing world. Potentials for equitable solutions are examined including priority steps and actions, appropriate treatment options and reliable forecasting methods for paediatric ARVs, as well as combination incentives to generic companies against market unattractiveness and enforced intellectual property (IP) rights. Moreover, implementation strategies to enhance the development and production of affordable ARV paediatric formulations and appropriate supply systems to ensure availability are investigated. RESULTS: The current market for FDC paediatric ARVs is already substantial and will only grow with improved and scaled up diagnosis and monitoring of children. This provides an argument for immediate increase of production and development of FDC ARVs for children. These formulations must be low cost and included in the list of Essential Medicines to avoid children continuing to lag behind in access to treatment. Access-oriented, long-term drug policy strategies with the ability to pass muster of governments, the UN system, as well as generic and research-based enterprises are needed to let children gain expanded and sustained access to FDC ARVs. Under the requirements listed above, IP-bound Voluntary License (VL) flexibilities do appear, if coupled with substantial combination incentives to generic firms, as a fitting tool into the needs. Policies must consider enhancing human resource capacity in the area of caregivers and social and health workers aiming to spread correct information and awareness on effectiveness and rationale of FDC ARVs for children. Policies should urge that paediatric ARV treatment programmes entwine with extant interventions on prevention of mother-to-child transmission, as well as with HIV treatment initiatives focused on mothers and household members. Policies, again, should consider centralising functions and pooling resources to help overcome drug supply barriers. WHO's brokering role in VL-based agreements between wealthy and developing country industries, as well as its technical guidance in setting international standards should not be waived while looking for sustained access to optimised ARV treatments for children. Strategies discussed in this paper, while taking unavoidability of marketing and profit rules into account, look closely into the trade and drug policy directions of China and India according to frontier crossing implications of their IP management trends as well as their multi-faceted penetration strategies of both the wealthy and under-served markets the world over. PMID- 17346133 TI - Cloning and characterization of functional subtype A HIV-1 envelope variants transmitted through breastfeeding. AB - Previous studies of HIV-1 variants transmitted from mother-to-infant have focused primarily on computational analyses of partial envelope gene sequences, rather than analyses of functional envelope variants. There are very few examples of well-characterized functional envelope clones from mother-infant pairs, especially from envelope variants representing the most prevalent subtypes worldwide. To address this, we amplified the envelope variants present in 4 mother-infant transmission pairs, all of whom were infected with subtype A and three of whom presumably transmitted HIV-1 during the breastfeeding period. Functional envelope clones were constructed, either encoding full-length envelope sequences from the mother and baby or by making chimeric envelope clones in a common backbone sequence. The infant envelope sequences were genetically homogeneous compared to the maternal viruses, and pseudoviruses bearing these envelopes all used CCR5 as a coreceptor. The infant viruses were generally resistant to neutralization by maternal antibodies present near the time of transmission. There were no notable differences in sensitivity of the mother and infant envelope variants to neutralization by heterologous plasma or monoclonal antibodies 2G12 and b12, or to inhibition by sCD4, PSC-RANTES or TAK779. This collection of viral envelopes, which can be used for making pseudotyped viruses, may be useful for examining the efficacy of interventions to block mother-infant transmission, including sera from vaccine candidates, purified antibodies under consideration for passive immunization and viral entry inhibitors. PMID- 17346134 TI - Reduction of anti-HIV-1 Gag immune responses during co-immunization: immune interference by the HIV-1 envelope. AB - Immunization with more than one immunogen (co-immunization) is an efficient regimen to induce immunity to multiple antigens. However, immune interference has been reported using multi-plasmid DNA immunizations. HIV-1 envelope (Env) and Gag gene products are the predominant immunogens used in current AIDS vaccines, although, few studies have evaluated possible immune interference when these two antigens are co-administered. Therefore, in this study, immune interference during co-inoculation was examined using DNA vaccines expressing lentiviral Envs and Gag from gene sequences optimized for efficient expression in mammalian cells (codon-optimized). BALB/c mice vaccinated in separate hind legs with each plasmid individually elicited high titer immune responses, however, when HIV-1 Env(gp120) and HIV-1 Gag(p55) DNA plasmids were co-inoculated, there was a reduction in the immune responses elicited to HIV-1 Gag(p55). To determine if the anti-HIV-1 Gag(p55) immune interference was specific to HIV-1 Env(gp120), mice were co immunized with plasmids expressing the surface envelope protein from two additional lentiviruses, Env(gp130)-SIV or Env(gp90)-EIAV, or a soluble form of hemagglutinin (sHA) from influenza virus and HIV-1 Gag(p55)- or SIV Gag(p55)-DNA. Interestingly, there was no reduction in anti-HIV-1 Gag(p55) immune responses using other lentiviral envelopes or the influenza sHA. Also, none of the lentiviral envelopes reduced anti-SIV Gag(p55) immune responses during co immunization. Therefore, anti-HIV-1 Gag immune interference appears specific to co-immunizations with HIV-1 Env(gp120) and may involve a yet undefined immunological mechanism(s). PMID- 17346135 TI - Synergistic effect of combined HIV/HCV immunogens: a combined HIV-1/HCV candidate vaccine induces a higher level of CD8+ T cell-immune responses in HLA-A2.1 mice. AB - Dual infections with HIV-1 and Hepatitis C virus (HCV) may proceed in concert to cause severe disease. HIV positive individuals that become infected with HCV advance more rapidly to AIDS than those that are infected with HIV-1 alone. In this study, HLA-A2.1 mice were immunized with a combination vaccine including HIV and HCV immunogens (polycistronic DNA + proteins) or vaccine containing either HIV or HCV immunogens. Mice immunized with the combined HIV/HCV regimen had similar antibody titers as the group receiving either the HIV-1 or HCV only regimen. Proliferative immune responses showed that mice receiving the combined HIV/HCV vaccine exhibited a three fold higher stimulation index (SI) to gp120 than mice immunized with the vaccine containing HIV alone. To determine whether our vaccine strategy induced Th1 or Th2 immune responses, IFN-gamma and IL-4/IL-5 were measured. The combined HIV/HCV vaccine induced a higher level of Th1 responses to HIV-1 gag protein compared with the other groups, as measured by IFN gamma production. Interestingly, detection of IFN-gamma by ELISPOT assay demonstrated that the combined HIV/HCV vaccine group had increased numbers of spot forming cells (SFC) to HIV-gp120 peptides when compared to that of the HIV-1 only vaccine group. The combined HIV/HCV vaccine group also showed an increase in SFC to HCV-core peptides in comparison with the group receiving the HCV only vaccine. Intracellular IFN-gamma staining confirmed the ELISPOT results and demonstrated that the combined HIV/HCV group had significantly higher percentages of HIV and HCV-specific CD8+ T cells in comparison to the groups receiving the HIV or HCV vaccines. These results suggest a new approach to maximize vaccine efficacy against HIV and HCV. PMID- 17346136 TI - Evidence for predominance of CCR5-using HIV-1 strains during highly active antiretroviral therapy. AB - BACKGROUND: Very little is known about the influence of Highly Active Antiretroviral Therapy (HAART) on the surface expression of CCR5 and CXCR4 with respect to receptor tropism and replication kinetics of autologous HIV strains, during continuous therapy and structured treatment interruption (STI) regimens. OBJECTIVES: The main objectives of this study were to assess whether continuous therapy and STI regimens had any modulatory effects on expression of CCR5 and CXCR4 on T lymphocytes. STUDY DESIGN: We studied 6 patients on continuous HAART, 4 patients on STI and 1 treatment-naive patient. Sequential peripheral blood mononuclear cells (PBMC) samples were analyzed to determine viral replication kinetics, the genotype influencing tropism of the autologous strain, in vitro co receptor usage patterns in relation to the surface expression of each co receptor. RESULTS: Our data suggest that predominant CCR5 expression and tropism, during therapy, but significant down-modulation of CXCR4 expression. During the off-therapy phases of STI, CXCR4 expression increased, which correlated with increased CXCR4 tropism of isolates from these time points. In-vitro tropism during therapy was consistent with the HIV-1 V3 genotype, which was characteristic of CCR5 using strains. CONCLUSIONS: These results suggest that certain HAART regimens influence the surface expression of CXCR4, which may have profound implications for antiretroviral treatment. PMID- 17346138 TI - Inter-clade cross-reactivity of HIV-1-specific T cell responses in human immunodeficiency virus type 1 infection in China. AB - To determine the degree of HIV-1-specific cytotoxic-T-lymphocyte (CTL) cross responses to the clade B and C consensus sequences at the single peptide level. We assessed CTL responses in 46 HIV-1 clade B chronically infected individuals using an interferon-gamma Elispot assay with a total of 826 overlapping peptides spanning HIV-1 clade B and C consensus sequences. In general, 583 peptides were recognized by HIV-1-specific T cells in the study subjects (292 clade B, 291 clade C respectively), of which 204 peptides in both clades were recognized simultaneously. The HIV-1-specific CTL responses to both clade peptides contributed 54.23% (954/1759) to the total responses. No significant difference was observed between the overall magnitude or frequency of CTL responses to clade B proteins and those to clade C proteins. According to the profiles of CTL magnitude and CTL frequency, the top 44 and 35 synthetic peptides were identified as immunodominant regions in the clade B and C consensus sequences respectively and 27 corresponding peptides in two immunodominant regions were cross-reactive. These peptides with cross-reactivity had a significantly higher ability to elicit CTL responses (P< 0.01) and preferentially had a trend of lower entropy and higher inter-clade homology. A wide degree of cross-clade reactivity of HIV-1 specific T cells exist in clade B and clade C variants. Most of immunodominant peptides with cross-reactivity are vigorous to elicit CTL responses and preferentially be conservative. This result may make future HIV-1 vaccines including multiple copies of CTL epitopes in these immunodominant peptides effective for this population. PMID- 17346137 TI - Drug resistance and viral evolution in plasma and peripheral blood cells during structured treatment interruption (STI) and non-interrupted HAART. AB - BACKGROUND: Highly active antiretroviral therapy (HAART) can successfully reduce plasma and tissue levels of HIV-1 RNA and results in reductions in HIV-related morbidity and mortality, but the slow viral evolution during therapy in cellular reservoirs is a continuing problem. In addition, little remains known how viral evolutionary process may differ between cell-free and cell-associated compartments, over time, in vivo in patients receiving HAART or STI. OBJECTIVES: The main objectives of this study were to assess viral replication kinetics, drug resistance and viral evolution during HAART and STI. STUDY DESIGN: We have conducted a longitudinal study of virus culture kinetics in vitro, molecular analysis of uncultured HIV-1 variants from plasma and PBMC of 6 patients on HAART, 4 patients on STI, and 6 from treatment-naive patients. RESULTS: Our data suggest that drug resistance mutations remained compartmentalized between plasma and PBMC. The divergent distribution of resistance mutations between plasma and PBMC coincided with divergent env gene evolution in these compartments. In contrast, the HIV strains from therapy-naive patients showed tight genetic and phylogenetic concordance between plasma and PBMC. Both STI and non-STI groups showed the presence of resistance mutations to both RT and protease inhibitors, which correlated with inadequate suppression of viremia and partially with the virus culture isolation in vitro. CONCLUSIONS: Overall, STI for HIV patients has no added advantage over regular HAART at the virologic level and in the diminution of resistance mutations that result in therapy failure. Under both forms of anti-retroviral therapies, virus could be isolated in vitro from the PBMC showing continuing low-level viral replication under suppressive therapy. Overall, these data may be useful in predicting the late emergence of drug resistance mutations via the latent integrated provirus. PMID- 17346139 TI - Anti-IgG antibodies from sera of healthy individuals neutralize HIV-1 primary isolates. AB - Immunoglobulins (Ig) of pooled healthy human sera were purified by affinity chromatography based on their reactivity with human IgG. This Ig fraction represent connected, natural antibodies (NAbs) and here are denoted as anti-IgG antibodies. The data revealed that IgG, IgA and IgM isotypes are constituents of anti-IgG fraction. The ability of anti-IgG antibodies to prevent infection of PBMC by HIV-1 was demonstrated. They exhibited different neutralizing activity depending on the phenotype of the tested virus. The efficacy of neutralization was comparable to monoclonal antibodies (MAbs) IgG1b12 at least for the HIV-1 (92HT593B) strain. These studies suggest that connected antibodies thus, constituents of immune network, could prevent infection by HIV-1. NAbs as essential components of therapeutic molecules of intravenous Ig (IVIg) have a beneficial effect on variety of immunological disorders by affecting the structure, function and dynamics of the immune network. Since, hallmark of HIV-1 infection are immunological disorders we hypothesizes that they might be corrected to some extend by anti-IgG antibodies. PMID- 17346140 TI - A study of tryptophan metabolism via serotonin in ventricular cerebrospinal fluid in HIV-1 infection using a neuroendoscopic technique. AB - In this paper we report the study of tryptophan metabolism via serotonin in ventricular CSF in HIV-1 infection in order to investigate the origin of tryptophan metabolites in the human brain. The patients (n=4) were affected with non-communicating hydrocephalus. One of these also was suffering from HIV-1 infection. The CSF was withdrawn from different sites of the cerebral cavity with a neuroendoscopic procedure which allows an accurate exploration of all the cerebral ventricles. The measurement of tryptophan, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, and melatonin was carried out by HPLC with fluorometric detection. In HIV-1 infection the highest concentration of tryptophan is present in the CSF of the choroid plexus; however, the levels are markedly lower than those in hydrocephalic individuals (control group). 5 Hydroxytryptophan CSF content is higher in HIV-1 infection than in hydrocephalic controls in all districts examined. Regarding serotonin, a great difference appears in the choroid plexus and in the pituitary recess between the HIV-1 infected patient and the control group. The values of 5-hydroxyindoleacetic acid are much lower in the CSF of the HIV-1 infected patient than in hydrocephalic controls. Melatonin levels appear to fluctuate largely but, in the HIV-1 infection, a great variability is present among the sites of CSF withdrawal. The third ventricle contains the highest concentration of melatonin and the choroid plexus and the pituitary recess the lowest. All the melatonin concentrations in HIV-1 infection are largely different than in hydrocephalic controls. This is the first report on the measurement of tryptophan metabolites via serotonin in ventricular CSF in HIV-1 infection. PMID- 17346141 TI - Fatal disseminated toxoplasmosis during primary HIV infection. AB - Toxoplasmosis is a well recognized manifestation of AIDS, but the disseminated disease is a rare condition and it has not been associated to HIV seroconversion to our knowledge. We describe a fatal episode of disseminated T. gondii acute infection with massive organ involvement during primary HIV infection. The serological data demonstrate primary T. gondii infection. The avidity index for HIV antibodies supports recent HIV-1 infection. PMID- 17346142 TI - Epicardial adipose tissue is related to carotid intima-media thickness and visceral adiposity in HIV-infected patients with highly active antiretroviral therapy-associated metabolic syndrome. AB - BACKGROUND: High cardiovascular risk and accelerated atherosclerosis are associated with human immunodeficiency virus (HIV). Recently, the use of highly active antiretroviral therapy (HAART) for the treatment of HIV infection is correlated with the development of HAART-associated metabolic syndrome and lipodystrophy (LDS). Detection of epicardial fat thickness, new index of visceral adiposity in non HIV-infected patients, might be important as diagnostic tool in HIV-infected patients on HAART. OBJECTIVE: Primary objective of this study was to evaluate whether echocardiographic epicardial adipose tissue is related to visceral adipose tissue (VAT) and Carotid Intima-Media Thickness (IMT), index of atherosclerosis in HIV-infected patients on HAART with LDS. DESIGN: We studied 60 consecutive HIV-infected subjects with HAART-associated metabolic syndrome and LDS and 45 HIV-infected subjects on HAART without LDS. MAIN OUTCOMES MEASURES: Epicardial fat thickness and IMT were measured by ultrasonography in both study and control groups. Magnetic resonance imaging (MRI) was used to calculate VAT in HIV-infected subjects on HAART with LDS. RESULTS: Epicardial adipose tissue thickness showed an excellent correlation with MRI-VAT (r=0.85; P<0.001) and IMT (r=0.78;P<0.001) in HIV-infected patients on HAART-with LDS. Multiple regression analysis showed that epicardial fat thickness was best predicted by MRI-VAT and IMT (R2=0.57, p<0.001 and p<0.01, respectively). HIV-infected patients with HAART associated metabolic syndrome and LDS showed higher epicardial fat thickness and IMT (8 vs 6.5 mm; 0.71 vs 0.66 mm, respectively, p<0.01 for both) than HIV infected subjects on HAART without LDS. CONCLUSION: Echocardiographic assessment of epicardial fat may have the potential to be a simple and reliable marker of visceral adiposity and increased cardiovascular risk in HIV-infected patients with HAART-associated metabolic syndrome and LDS. PMID- 17346143 TI - DNA repair helicases as targets for anti-cancer therapy. AB - The genetic complexity of cancer has posed a formidable challenge to devising successful therapeutic treatments. Tumor resistance to cytotoxic chemotherapy drugs and radiation which induce DNA damage has limited their effectiveness. Targeting the DNA damage response is a strategy for combating cancer. The prospect for success of chemotherapy treatment may be improved by the selective inactivation of a DNA repair pathway. A key class of proteins involved in various DNA repair pathways is comprised of energy-driven nucleic acid unwinding enzymes known as helicases. DNA helicases have been either implicated or have proposed roles in nucleotide excision repair, mismatch repair, base excision repair, double strand break repair, and most recently cross-link repair. In addition to DNA repair, helicases have been implicated in the cellular processes of replication, recombination, transcription, and RNA stability/processing. The emerging evidence indicates that helicases have vital roles in pathways necessary for the maintenance of genomic stability. In support of this, a growing number of human genetic disorders are attributed to mutations in helicase genes. Because of their essential roles in nucleic acid metabolism, and more specifically the DNA damage response, helicases may be a suitable target of chemotherapy. In this review, we have explored this hypothesis and provided a conceptual framework for combinatorial treatments that might be used for combating cancer by inhibiting helicase function in tumor cells that already have compromised DNA repair and/or DNA damage signaling. This review is focused on helicase pathways, with a special emphasis on DNA cross-link repair and double strand break repair, that impact cancer biology and how cancer cells may be chemosensitized through the impairment of helicase function. PMID- 17346144 TI - Pgp and FLT3: identification and modulation of two proteins that lead to chemotherapy resistance in acute myeloid leukemia. AB - Acute myeloid leukaemia (AML) comprises 80% of acute adult leukaemias and the disease has mostly an unfavourable outcome. Diagnostic criteria rely primarily on morphological classification, while prognostic evaluation is determined by cytogenetic methods. Survival is highly variable and it is a matter of debate, whether alternative therapeutic approaches may improve the effectiveness of conventional cytotoxic drug treatment. Two transmembrane proteins undoubtedly contribute to worse prognosis: P-glycoprotein (Pgp) and FLT3. Pgp is a transmembrane, ATP-cassette binding efflux pump that efficiently removes structurally unrelated xenobiotics from leukaemic blasts. This leads to inefficiency towards several cytotoxic drugs, hence the phenomenon is called multidrug resistance. FLT3 is a transmembrane tyrosine kinase and an internal tandem duplication can considerably augment its kinase activity. Both mechanisms lead to chemotherapy resistance and significantly shorter survival; thus several studies have been designed to treat patients via therapeutic measures that neutralize these proteins. This review focuses on the pathophysiological phenomena and the detection methods of Pgp and FLT3 as well as on novel therapeutic strategies that are offered by their inhibition. PMID- 17346145 TI - Synthetic peptides for the immunodiagnosis of human diseases. AB - Synthetic peptides have been shown to be valuable tools for viral laboratory diagnosis and can provide uniform, chemically well-defined antigens for antibody analysis, reducing inter- and intra-assay variation. The main aim in the development of peptide-based diagnostic tests is to recognise specific antibodies induced by the whole viral proteins but using selected short fragments containing the most potent antigenic determinants. The success of this approach depends on the extent to which synthetic peptides are able to mimic the immunodominant epitopes of antigens. In recent years, synthetic peptides that mimic specific epitopes of infectious agents' proteins have been used in diagnostic systems for various human diseases. The present review summarizes some of the drawbacks of the use of relatively short linear peptides as antigenic substrates and the subsequent chemical strategies developed in order to overcome the low peptide reactivity against specific antibodies. Moreover, it outlines the most significant bibliography published in the last five years which provides validated peptide based tests potentially useful for diagnosis of viral, bacterial, parasitic and autoimmune diseases. PMID- 17346146 TI - Chronic HCV-related autoimmunity: a consequence of viral persistence and lymphotropism. AB - Hepatitis C virus (HCV)-host interaction, namely the host immune reaction against various viral proteins, determines viral persistency and the severity of liver damage. The strong lymphotropism of HCV has been proven to be responsible in part for its ability to evade the peripheral immune response and possibly the frequency of HCV-related autoimmunity. Various mechanisms were reported to be responsible for HCV persistency and its association with autoimmunity. Of these, enhanced T cell apoptosis was reported to contribute to viral persistency and disease severity. The issue of HCV-related autoimmunity has partly been shown to be related to the resistance of CD5+ B cell subpopulation to apoptosis. Autoimmunity has been reported by many to include a wide range of autoantibodies such as rheumatoid factor, ani-cardiolipin and smooth muscle antibodies. In this review our aim is to summarize the data on the mechanisms responsible for HCV persistence and HCV-related autoimmunity. We will try to determine the importance of autoimmunity in the evaluation of chronic HCV infected patients. PMID- 17346147 TI - Building a bridge between clinical and basic research: the phenotypic elements of familial predisposition to type 1 diabetes. AB - Familial aggregation has been shown for type 1 diabetes (T1D) although the nature of the factors (environment and/or genetics) responsible remains unclear. Familial clustering of diabetic nephropathy as well as of increased cardiovascular morbidity and early mortality has also been observed. This review describes the nearly 20 years history of our investigation in parallel with contemporary literature. The story is presented from the early years' strong focus on possible markers of T1D nephropathy (urinary albumin, urinary enzymes, erythrocyte Na/Li countertransport, and erythrocyte Na/H exchange) to the last clinical investigations to determine relevant biological markers of familial predisposition to T1D. Our studies of case-families recruited unaffected first degree relatives of sporadic T1D cases and population-based controls. Unlike multiple-case families, these families are those less likely to carry a strong genetic predisposition. Participants were both interviewed and provided biological material for a detailed functional characterisation of their biochemical phenotype. These studies have initially excluded that the erythrocyte Na/H exchange could be a marker of diabetic nephropathy. On the contrary, NHE activity was significantly higher in T1D family members independently of the presence of renal disease. Basic science knowledge of NHE and its functional implications have also been reviewed. Unexpectedly, we found evidence of increased oxidative stress in nondiabetic normotensive relatives of T1D patients, apart from soluble markers of autoimmunity and despite seemingly intact antioxidant defences. Markers of oxidation were associated with markers of inflammation and we concluded that the familial increase in NHE activity could be ascribed to the direct stimulatory effect of oxidative stress. Relatives showed also immunological hallmarks and cardiovascular abnormalities that were related to indices of oxidative stress and metabolic syndrome. Other peculiarities emerged from measuring the erythrocytes redox system that exports electrons across the cell membrane to external oxidants as a function of cytoplasmic electron donor concentration. This electron transfer might reflect the functional state of membrane proton pumps that modulate intracellular redox levels. The transport system contributed to oxidation in T1D families, whereas in healthy people it protected from oxidation. Furthermore, dietary intake of vitamin C and sporting activities modulated erythrocyte electron transfer efficiency. The contribution of environmental factors was investigated using the European Prospective Investigation of Cancer and Nutrition questionnaires that provided evidence of common unhealthy dietary behaviours, which could even predispose to the development of diabetes and cardiovascular complications, in subjects living in Pisa. However, lifestyle of T1D relatives was indistinguishable from those of controls, except for the higher daily intake of niacin and the lower physical activity levels. No difference in smoking or alcohol consumption emerged among families and controls. The oxidative stress is a non-specific though certain component of pathogenesis at numerous diseases states of aerobic organisms. Although molecular genetic analysis has produced significant progress in T1D phenotype, much remains to be learned about the molecular sequence of events leading from a generic familial pro-oxidant background to a sporadic form of T1D (where oxidative damage targets the insulin-secreting cells). PMID- 17346148 TI - Genetics of gestational diabetes mellitus. AB - About 2-5% of all pregnant women develop gestational diabetes mellitus (GDM) during their pregnancies and the prevalence has increased considerably during the last decade. GDM is a heterogeneous disorder that is defined as carbohydrate intolerance with onset or first recognition during pregnancy. It is manifested when pancreatic beta cells are no longer able to compensate for the increased insulin resistance during pregnancy, but the pathogenesis of the disease is still largely unknown. GDM is considered to result from interaction between genetic and environmental risk factors. Genetic predisposition to GDM has been suggested since GDM clusters in families. Also, women with mutations in MODY (Maturity onset diabetes of the young) genes often present with GDM. In addition, common variants in several candidate genes (e.g. potassium inwardly rectifying channel subfamily J, member 11 [KCNJ11], Glucokinase [GCK], Hepatocyte nuclear factor 1alpha [HNF1A] etc.) have been demonstrated to increase the risk of GDM. Old age, obesity and high fat diet represent some important non-genetic factors. There are several approaches to search for genes predisposing to a polygenic disease like GDM including linkage and association studies, expression profiling and animal models. A combination of several methods is usually necessary. Identification of the underlying genetic causes of GDM will eventually give a better view of the mechanisms that contribute to the pathophysiology of the disease. Furthermore, it may improve options to possibly prevent GDM and complications for the mother and her child. This review focuses on the genetics of GDM and possible implications in clinical practice. PMID- 17346149 TI - Cardiovascular cGMP-generating systems in physiological and pathological conditions. AB - The intracellular messenger cyclic GMP (cGMP) represents the key signal in several transduction pathways throughout the animal world. In the heart cGMP signaling contributes to functional interaction of different cell types. Nitric oxide (NO) and natriuretic peptides (NPs), major autocrine-paracrine cardiovascular regulators, increment intracellular cGMP through guanylate cyclases (GCs). NO and NPs interact with two GC types: cytosolic (soluble: sGC) and membrane bound [particulate: pGC (NP receptor types A and B)], respectively. Depending on sub-cellular localization and regulation of the enzymes, cGMP produced by either pGC or sGC exerts different complementary effects. The two pathways are reciprocally regulated. NPs-depending pGC is modulated by NO-cGMP signaling, and the activity of NO is influenced by cellular concentrations of both NO itself and NPs. This heterologous feedback regulates GCs, linking cardiovascular autocrine-paracrine activities of NPs and NO. Importance of these cGMP converging routes goes far beyond their role under normal conditions. They are of relevance especially in disease states when tissue and circulating levels of NPs, and local NO production are altered. An example is the endothelial dysfunction associated with deficient NO production and uncoupled endothelium myocardium communications. In this case, NPs-pGC-cGMP could supplement the reduced activity of NO-scGC-cGMP pathway. In addition, these systems regulate cell growth and apoptosis, playing a role in myocardial pathological morpho functional remodeling. Here we will review recent concepts on NO/NPs dependent control of heart function in vertebrates, also focusing on cGMP-activated downstream signaling and its role in health and disease conditions. PMID- 17346150 TI - Signaling through RAS-RAF-MEK-ERK: from basics to bedside. AB - Aberrant signaling caused by mutations in the RAS-RAF-MEK-ERK pathway and its upstream activators critically contributes to human tumor development. Strategies, which aim at inhibiting hyperactive signaling molecules, appear conceptually straight forward, but their translation into clinical practice has been hampered by many setbacks. Understanding structure, function and regulation of this intracellular pathway as well as its crosstalk with other signaling activities in the cell will be essential to ensure reasonable usage of new therapeutic possibilities. This review provides an understanding of this signaling cascade as revealed by genetic and biochemical approaches and discusses the existing or arising possibilities to interfere with unphysiological activation in cancer. Signaling aberrations and signal transduction therapies will be discussed exemplary for two types of hematological neoplasia, acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS). In the future understanding the role of tumor stem cells, both as a source of tumor recurrence and tumor heterogeneity, the signals controlling their fate as well as epigenetic changes in cancer will be the next critical steps to further advance the applicability of these novel therapeutic strategies. PMID- 17346151 TI - Microscopic simulation in biology and medicine. AB - Mathematical models are finding an increasing use in bio-medical scientific investigations as effective means of putting the interpretation of biological phenomena on a more quantitative basis. Besides the well established mathematical paradigm based on differential equations, another approach that takes full advantage of the steadily increasing computing power, is gaining increasing consensus: micro-simulation. Micro-simulation is based on the idea of mimicking the behavior of the system under investigation through the specification of the rules of interaction among its individual constituents. This rule-driven (sometimes called equation-free) approach allows a smoother upgrade of models sophistication and reduces the gap between the abstract level of description typical of mathematical models and the complexity of the biological world. In this article we aim at illustrating, through specific examples, some of the potential advantages that micro-simulation has to offer in order to gain a better grasp and understanding of complex phenomena in biology and medicine. PMID- 17346152 TI - The structure and main functions of aminopeptidase N. AB - Aminopeptidase N (APN)/CD13 is a type II metalloprotease that belongs to the M1 family of the MA clan, which consists of 967 amino acids with a short N-terminal cytoplasmic domain, a single transmembrane part, and a large cellular ectodomain containing the active site. APN has a molecular weight of 110,000. The APN exists in two forms, namely the membrane aminopeptidase N and the soluble aminopeptidase N. Moreover, it exhibits the presence of various isozymes with different functions. APN is a ubiquitous enzyme present in a wide variety of human organs, tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). It is a multifunctional enzyme, related with tumorigenesis, immune system, pain etc. Furthermore, it also serves as a receptor for coronaviruses and other human viruses. Besides the manifestation of various other functions, APN is also involved in the trimming of antigen and the process of antigen presentation. These functions facilitate the modulation of bioactive peptide responses (pain management, vasopressin release) and influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis) thereby providing treatment options for many kinds of diseases. This review will introduce the structure and main functions of APN briefly. PMID- 17346153 TI - The Janus face of CD4+CD25+ regulatory T cells in cancer and autoimmunity. AB - Regulatory T cells (Treg) encompass a heterogeneous family of T cells implicated in maintenance of tolerance to self antigens. Treg cells might be qualitatively and/or quantitatively deficient in human autoimmune diseases, including multiple sclerosis, graft versus host disease, systemic lupus erythematosus, type I diabetes, and rheumatoid arthritis. In animal models of autoimmunity, infusion of ex vivo-expanded Treg cells and/or in vivo enhancement of Treg cell suppressor function by pharmacological agents and cytokines attenuate disease manifestations and restore tolerance. However, Treg cells represent a double-edged sword, as Treg cells with specificity for tumour-associated antigens contribute to cancer pathogenesis and progression. In vivo depletion of Treg cells by monoclonal antibodies and/or selected drugs is an encouraging therapeutic strategy which improves tumour eradication in animal models of cancer. In addition, elimination and/or functional inactivation of Treg cells might boost anti-tumour immunity in tumour-bearing hosts receiving anti-cancer vaccination. The present review discusses Treg cell manipulation as a novel therapeutic strategy in cancer and autoimmunity, conditions characterised by a common regulatory basis. PMID- 17346154 TI - Perspectives in biomolecular therapeutic intervention in cancer: from the early to the new strategies with type I interferons. AB - Interferon (IFN) was the first cytokine produced by recombinant DNA technology used in wide-spread clinical treatment of infectious diseases as well as malignancies. The IFN clinical potential was clearly realized from the outset. However, IFN represents one of the most controversial drugs of our time, as remarkable cycles of promise and disappointment have affected its development and use. Considerable evidence regarding anti-tumor activities of IFNs has been reported. In this paper we focus on molecular bases of the IFN system that may relate to its antitumor activities. Many of the numerous genes transcriptionally activated by IFNs have been shown to encode proteins that activate immune recognition of tumor cells, directly or indirectly exert tumor suppressor activity and/or control tumor cell cycle and programmed cell death. In addition, a physiological relevant function for endogenous type I IFN in cancer immunoediting process and a new way to IFN clinical use based on gene therapy or vaccine-like approaches have recently been suggested. The identification of selected tissue-specific and/or tumor-specific target pathways as well as of different type I IFN tumor escape and resistance mechanisms may provide novel approaches in the search for new IFN-based therapeutic strategies to circumvent cancer disease or improve clinical outcome. Promising IFN treatment has been recently defined by using novel pharmaceutical preparations with a more favourable pharmacokinetic response, also in combination with other bioreagents or other modalities of therapy. Translational research, linking both basic and clinical research, will lead to a new rationale for the use of IFN in cancer therapy. PMID- 17346155 TI - The antitumoral mode of action of imiquimod and other imidazoquinolines. AB - Imiquimod, the lead compound of the imidazoquinoline family of nucleoside analogues, has shown good efficacy against a variety of tumors of different origin. The mode of action of imiquimod and related compounds, which we have begun to understand in some detail in recent years, is complex and interesting inasmuch as it appears to comprise several presumably mutually enhancing components. Predominant amongst its actions is the induction of pro-inflammatory cytokines through agonistic activity towards Toll-like receptor (TLR)-7 and TLR 8, and consecutively, activation of the central transcription factor NF-kappaB. This activity stimulates the production of pro-inflammatory cytokines, chemokines and other mediators resulting in activation of antigen-presenting cells and the mounting of a profound Th1-weighted antitumoral cellular immune response. In addition, there are a number of secondary effects on the molecular and cellular level that can be explained through the activation of NF-kappaB. The pro inflammatory activity of imiquimod appears to be augmented by suppression of a negative regulatory feedback mechanism which normally limits inflammatory responses. This is achieved independent of TLR-7 and TLR-8 through interference with adenosine receptor signaling pathways, particularly the A(2A) subtype, and receptor-independent reduction of adenylyl cyclase activity. Finally, at higher, albeit therapeutically relevant concentrations, imiquimod exerts a pro-apoptotic activity against tumor cells. Induction of apoptosis by imiquimod appears to be dependent on Bcl-2 proteins and involves caspase activation. The combination of multiple, presumably synergistic anti-tumoral functions by a single compound represents an interesting principle of pathogenesis-oriented, anti-neoplastic therapy. PMID- 17346156 TI - Human multidrug transporter ABCG2, a target for sensitizing drug resistance in cancer chemotherapy. AB - Human ABCG2, a member of the ATP-binding cassette transporter superfamily which transports a wide variety of substrates, is highly expressed in placental syncytiotrophoblasts, in the canalicular membranes of liver, in the apical membrane of the small intestine epithelium, and at the luminal surface of the endothelial cells of human brain micro vessels. This strategic tissue localization indicates that ABCG2 plays an important role in absorption, distribution, and elimination of xenobiotics and drugs. High ABCG2 expression has also been detected in many hematological malignancies and solid tumors, indicating that ABCG2 is likely responsible also for the multidrug resistance in cancer chemotherapy. Indeed, ABCG2 can actively transport structurally diverse conjugated- or unconjugated-organic molecules and various anticancer drugs. Many chemo-sensitizing agents have been discovered, which can be developed for increasing drug adsorption and reversing drug resistance in cancer chemotherapy by inhibiting ABCG2 function or expression. This review summarizes current knowledge on ABCG2, its relevance to multidrug resistance and drug disposition, and its ever-growing numbers of substrates and inhibitors. PMID- 17346157 TI - Insights into oxidative stress: the isoprostanes. AB - Oxidative stress, characterized by an imbalance between increased exposure to free radicals and antioxidant defenses, is a prominent feature of many acute and chronic diseases and even the normal aging process. However, definitive evidence for this association has often been lacking due to recognized shortcomings with methods previously available to assess oxidant stress status in vivo in humans. Several in vitro markers of oxidative stress are available, but most are of limited value in vivo because thay lack sensitivity and/or specificity or require invasive methods. Isoprostanes (IsoPs) are prostaglandin (PG)-like compounds that are produced in vivo independently of cyclooxygenase enzymes, primarily by free radical-induced peroxidation of arachidonic acid. F(2)-IsoPs are a group of 64 compounds isomeric in structure to cyclooxygenase-derived PGF(2alpha). Other products of the IsoP pathway are also formed in vivo by rearrangement of labile PGH(2)-like IsoP intermediates including E(2)- and D(2)-IsoPs, cyclopentenone A(2)- and J(2)-IsoPs, and highly reactive acyclic-ketoaldehydes (isoketals). Oxidation of docosahexaenoic acid, an abundant unsaturated fatty acid in the central nervous system, results in the formation of IsoP-like compounds, termed neuroprostanes. Measurement of F(2)-IsoPs is the most reliable approach to assess oxidative stress status in vivo, providing an important tool to explore the role of oxidative stress in the pathogenesis of human disease. Moreover, F(2)-IsoPs and other products of the IsoP pathway exert potent biological actions both via receptor-dependent and independent mechanisms and therefore may be pathophysiological mediators of disease. Measurement of F(2)-IsoPs may provide a uniquely valuable approach to understanding of the clinical pharmacology of antioxidants. PMID- 17346158 TI - Current drug targets and future therapy of pulmonary arterial hypertension. AB - During the last few decades, we have witnessed major improvements in the therapy of pulmonary arterial hypertension (PAH). PAH is characterized by abnormal remodeling of the pulmonary artery (PA) and increased PA pressures, resulting in a high premature mortality. Intravenous epoprostenol was the first effective approach toward improving the symptoms and survival of PAH patients. New prostanoids have also exhibited substantial clinical benefits; however, their long-term effects are under investigation. Endothelin-receptor antagonists and sildenafil have increased the lineup of therapeutic options against PAH. Combination therapy using these drugs is promising and is currently undergoing scrutiny in large clinical trials. An extensive analysis of the molecular mechanisms of PAH will produce novel targeted therapies. Most of the promising molecules target the inflammatory and proliferative processes underlying pathological PA remodeling. Interestingly, drugs used for other diseases, such as statins, Rho-kinase inhibitors, imatinib mesylate, may control the pathological vascular remodeling of PAH. Gene and cell therapy using vectors expressing prostacyclin synthase, endothelial nitric oxide synthase, or vascular endothelial growth factor are also promising strategies. However, the efficacy and safety of these approaches should be further tested in clinical trials. Genetic studies revealed some crucial genetic dispositions of familial PAH, although their pathobiological roles have not yet been fully clarified. Collaboration for integrated research will address these issues and generate greater clinical benefits for PAH patients. PMID- 17346159 TI - The importance of c-Kit and PDGF receptors as potential targets for molecular therapy in breast cancer. AB - Molecular therapies target key functional molecules in order to halter viable operation of cancer cells. Receptor tyrosine kinases (RTKs) constitute attractive targets, as quite often their abnormal signaling has been associated with tumor development and growth. Overexpression of growth factor receptors, including IGF, EGF, TGF-alpha, SCF and PDGF receptors, has been associated with poor prognosis in breast cancer. Therefore, a number of RTKs are already targets for novel designed drugs, which involve tyrosine kinase inhibitors and monoclonal antibodies. Despite the fact that c-Kit and PDGF-R have been effective targets in a number of cancers, the experimental results in breast have not yet clarified their importance. The expression and function of c-Kit in breast cancer is a quite controversial subject. Several studies propose that the loss of c-Kit expression has been associated with tumor progress, whereas other reports indicate not only its expression but also the implication of c-Kit in breast cancer. On the other hand, the expression of PDGF-R in breast cancer is not in question. A number of inhibitors against tyrosine kinases are currently in trials as to demonstrate their importance in breast cancer treatment. Imatinib (STI571), which is a selective tyrosine kinase inhibitor and particularly of c-Kit and PDGF R, exhibited encouraging results in respect to its inhibitory effect in cell growth and invasion potential in a panel of human breast cancer cell lines. In this review, the importance of RTKs in human cancer and of c-Kit and PDGF-R as molecular targets in breast cancer treatment, in the view of their expression profiles and the in vitro effects of STI571 is discussed. PMID- 17346160 TI - The effect of ageing on cytochrome p450 enzymes: consequences for drug biotransformation in the elderly. AB - Ageing is an aggravating factor leading to alterations in the biotransformation of drugs, and therefore their therapeutic efficacy and safety. In this review we discuss the influence of ageing on drug metabolizing enzymes in male Wistar rats. We report that drug metabolizing enzymes can be affected by ageing either by post translational modifications or by transcriptional modifications. The post translational modifications could be due to an increase of oxidative stress during ageing. Although it is now well established that transcriptional modifications are due to a change in the GH secretion profile in senescent rats, the intracellular mechanisms underlying these modifications are still unclear. In addition to the strong decrease in the activity of the main CYPs of male rats, we discuss the potential consequences on human drug metabolism in the elderly. PMID- 17346161 TI - Recent advances in antimalarial compounds and their patents. AB - Malaria is one of the most severe tropical parasitic disease causing 1-3 million deaths annually. In the last 25 years very few new antimalarial molecules have been developed and only a limited number of them are currently in various stages of clinical development. The presently available antimalarial drugs include artemisinin analogs, quinoline derivatives and antifolates. This review summarizes recent advances in antimalarial drug development and world patents published between 2000-2006 claiming new synthetic antimalarial compounds and their activities. The most over-represented classes of compounds in malaria patent literature in order of frequency are artemisinin analogs, quinoline derivatives, DOXP reductoisomerase inhibitors, antifolates and febrifugine analogues. Many of these patents describe the novelty and potential of these synthetic derivatives with an attempt to identify the next generation antimalarials that may have potential commercial advantages. PMID- 17346162 TI - The search for a topical dual action spermicide/microbicide. AB - There is an urgent clinical need to research novel methods of fertility control that are also protective against sexually transmitted diseases (STDs) such as the human immunodeficiency virus (HIV) or Chlamydia. The most obvious way to generate such a dual-purpose contraceptive method would be to develop safe, effective spermicides that were also active against a wide range of pathogenic organisms. The currently available formulations such as nonoxynol-9, gramicidin and benzalkonium chloride are effective spermicides but are toxic to the vaginal epithelium and do not provide protection against STDs. Over 60 agents are in clinical trials as potentially safer topical spermicides and/or microbicides. Compounds that have reached this stage of development include acid buffers, detergents, dendrimers, non-nucleoside reverse transcriptase inhibitors and anionic polymers. In addition, a number of potential spermicides/microbicides are the subject of preclinical investigation, including beta-cyclodextrin, cyanovirin, porphyrins, cyclotriazadisulfonamides, dermaseptins, short interfering RNA (siRNA) and HIV antibodies. The chemical principles underlying these disparate approaches and potential avenues for future investigation are discussed. PMID- 17346163 TI - Inflammation in chronic obstructive pulmonary disease: implications for new treatment strategies. AB - Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease but current predictions are that it will continue to rise as an important cause of mortality and morbidity worldwide. COPD is a complex inflammatory disease with both airway and parenchymal lung injury. Currently there is growing recognition that the inflammatory response extends beyond the lung, with evidence of systemic inflammation, which may account for the multi-organ effects associated with COPD. Early diagnosis and timely therapeutic intervention are likely to make a significant contribution to tackling this disease. Smoking cessation remains the single most effective means of preventing lung function decline and reducing mortality. At present, no currently available drugs have been shown to slow the progression of the disease. Pharmacological treatment has focused largely on symptomatic relief and short-acting bronchodilators have been the mainstay therapy. Long-acting beta-2 agonists and anti-cholinergics have provided additional benefit and anti-inflammatory agents such as inhaled corticosteroids and theophylline seem to offer benefit in selected patients. Combinations of the different classes of treatment, particularly in the same inhaler device, seem to confer particular advantage with improvements in symptoms, exercise capacity, health status and reductions in exacerbations. More research is needed to unravel the important cellular and molecular processes involved in the pathophysiology of COPD and ultimately to develop new and more effective forms of therapy. PMID- 17346164 TI - Survival factors from activated accessory cells and their role in triggering autoimmune diseases. AB - To maintain immune homeostasis, the immune system has evolved two "opposite" mechanisms to regulate the activation or expansion of effectors including potential auto-reactive lymphocytes following an immune response. One is to support the survival of activated effectors and thereby benefit the generation of memory response. However, an inappropriate survival of auto-reactive lymphocytes may lead to autoimmune diseases, e.g. multiple sclerosis (MS) and rheumatoid arthritis (RA). The other is to induce apoptosis of most activated effectors, thereby bringing the immune system to a baseline level after an immune response. It is known that autoimmune diseases are due to uncontrolled growth of auto reactive lymphocytes, eventually leading to damage of self-tissues or organs. Control of auto-reactive T lymphocytes therefore constitutes an attractive therapeutic strategy. Many studies on accessory cells and their secreted factors have focused on their role in the effector phase of a specific autoimmune disease. Recent data, however, support their causative role in triggering autoimmune diseases. In the past several years, several cytokines from activated accessory cells were demonstrated to promote the survival of pathogenic auto reactive lymphocytes in animal models of MS, RA, and other autoimmune diseases. This review therefore focuses on the current knowledge regarding the role of those soluble survival factors in the initiation of different autoimmune diseases. PMID- 17346165 TI - Some recent insights into the prothrombogenic mechanisms of antiphospholipid antibodies. AB - Antiphospholipid antibodies (aPL) are a heterogeneous group of autoantibodies, detected in the sera of patients with both autoimmune and various non-autoimmune diseases. They are also detected in subjects with no overt underlying disease - the primary antiphosphilipid syndrome (PAPS). High titers of APL are associated with arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia. There have been many suggestions explaining the potential mechanisms of the procoagulant effect of aPL. These include endothelial cell (EC) activation; increased adhesion molecule expression; inhibition of EC prostacyclin release, increased leucocyte adhesion to EC, downregulation of thrombomodulin expression. APL induce the procoagulant activity of monocytes via increased tissue factor expression and directly stimulate platelet hyperactivity with resultant production of enhanced amounts of the proaggregatory molecule of TXA(2). In vitro studies show that prepro-endothelin-1 mRNA is induced by human monoclonal anticardiolipin antibodies and this might contribute to vasospasm, and, ultimately, to arterial occlusion. The hypercoagulable state in APS patients is associated with alterations in the protein C/S pathway. It is suggested that aPL may impair the protein C anticoagulant system. Acquired protein C and protein S deficiency is described in patients with APS. Beta2- glycoprotein I, (Beta2-GPI) a natural anticoagulant, is involved in the regulation of protein S anticoagulant activity by preventing the binding of protein S to C4b-binding protein. APL were shown to inhibit this effect of Beta2- GP I. As the group of aPL is very heterogeneous, it is unlikely that a single mechanism is responsible for the thrombogenic activity of all aPLs associated with thrombosis. PMID- 17346166 TI - SAR and QSAR of the antioxidant activity of flavonoids. AB - Flavonoids are a group of naturally occurring phytochemicals abundantly present in fruits, vegetables, and beverages such as wine and tea. In the past two decades, flavonoids have gained enormous interest because of their beneficial health effects such as anti-inflammatory, cardio-protective and anticancer activities. These findings have contributed to the dramatic increase in the consumption and use of dietary supplements containing high concentrations of plant flavonoids. The pharmacological effect of flavonoids is mainly due to their antioxidant activity and their inhibition of certain enzymes. In spite of abundant data, structural requirements and mechanisms underlying these effects have not been fully understood. This review presents the current knowledge about structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs) of the antioxidant activity of flavonoids. SAR and QSAR can provide useful tools for revealing the nature of flavonoid antioxidant action. They may also help in the design of new and efficient flavonoids, which could be used as potential therapeutic agents. PMID- 17346167 TI - Designing recombinant vaccines with viral properties: a rational approach to more effective vaccines. AB - One of the great demands and challenges for vaccination is to successfully target the pathogens responsible for much of mankind's chronic disease burden including: AIDS, infectious hepatitis, tuberculosis and malaria. Another is realizing the potential of therapeutic immunization to cure diseases such as cancer, allergy and inflammatory autoimmunity. To achieve these objectives, the fundamental insights gained from immunology, genomics, molecular-cellular biology and vaccinology must be implemented in order to develop more effective, better defined and safer vaccines. As an illustrative example of this we examine the key features of viruses that are known to be responsible for eliciting superb host immune responses. These insights have formed a basis for understanding the effectiveness of existing vaccines and provide a framework for designing and developing new vaccines better able to meet pressing unmet medical needs. The key immunogenic properties of viruses that are understood to date and are currently being applied include: their particulate nature, their highly repetitive and ordered structures, their ability to induce innate immunity with consequent conditioning of adaptive responses and the kinetics and distribution of viral antigens during infection. Vaccines and vaccine-formulations recently registered for use in humans already incorporate some of these elements. Of great anticipation is the progress of the next-generation vaccines now advancing through the various stages of research and development. Vaccines which, by way of rational design, incorporate viral properties to induce tailored responses and thus have the potential to provide safer and more effective prophylaxis and therapies. PMID- 17346168 TI - Hematopoietic cytokines--on the verge of conquering neurology. AB - Two hematopoietic cytokines are currently gaining increasing attention within neurological research. Erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) have long been known for their ability to induce the proliferation of certain populations of hematopoietic lineage cells. However, it has recently been found that EPO, G-CSF, and their respective receptors are also expressed in the human central nervous system (CNS) and may be an important part of the brain's endogenous system of protection. Both hematopoietic cytokines have been shown to have neuroprotective potential in a variety of animal disease models both in vitro and in vivo, through the inhibition of apoptosis, induction of angiogenesis, exertion of anti-inflammatory and neurotrophic effects, as well as by the enhancement of neurogenesis. EPO and G-CSF have been extensively studied in the context of hematological disorders and have recently been successfully applied in the first clinical trials in stroke patients. Intravenous high-dose EPO therapy was associated with an improvement in the clinical outcome and preclinical studies with intravenous high-dose G-CSF therapy have clearly shown that it has considerable neuroprotective potential in the acute, as well as in the chronic phase of stroke. In this review, the current knowledge of the neuroprotective mechanisms of EPO and G-CSF is summarized with regard to in vitro and in vivo data. Focus is placed on the role of EPO in neurological disease models with an emphasis on its influence on functional outcome. New experimental results are assessed in detail and correlated with the findings of recent clinical studies. PMID- 17346169 TI - Mechanisms of CD4 downregulation by the Nef and Vpu proteins of primate immunodeficiency viruses. AB - Human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), and simian immunodeficiency virus (SIV) are the etiological agents of acquired immunodeficiency syndrome (AIDS) in humans and a related disease in non human primates. These viruses infect T cells and macrophages that express the surface glycoprotein, CD4, because this glycoprotein acts as a co-receptor for incoming virus particles. Once infection has occurred, however, the presence of CD4 poses problems for the virus life cycle, including the possibility of superinfection, premature binding of CD4 to nascent virus particles, and inhibition of virus release. Accordingly, primate immunodeficiency viruses have evolved at least two distinct mechanisms, mediated by the Nef and Vpu viral proteins, to "downregulate" CD4 in the host cells. Nef and Vpu are mainly expressed early and late, respectively, in the viral life cycle, ensuring continuous removal of CD4. Nef links mature CD4 to components of clathrin dependent trafficking pathways at the plasma membrane, and perhaps in intracellular compartments, leading to internalization and delivery of CD4 to lysosomes for degradation. Vpu, on the other hand, interacts with newly synthesized CD4 in the endoplasmic reticulum, linking CD4 to the SCF ubiquitin ligase and facilitating the entry of CD4 into the endoplasmic-reticulum associated degradation pathway. These two mechanisms lead to a dramatic reduction of CD4 expression in infected cells and are essential for efficient virus replication and disease progression. PMID- 17346170 TI - Molecular mechanisms of resistance to antiviral therapy in patients with chronic hepatitis B. AB - Similar to the human immunodeficiency virus (HIV), the hepatitis B virus (HBV) replicates via reverse transcription, in this case, within infected hepatocytes. Substantial advances have been achieved in the past ten years in developing and utilizing nucleoside/nucleotide analog drugs to inhibit HBV replication. Most are chain terminators that interfere with one or more steps in the replication cycle. Four of them (lamivudine, adefovir dipivoxil, entecavir, and telbivudine), have been approved by the United States Food and Drug Administration (FDA) for the treatment of chronic hepatitis B (CHB). In clinical trials of HBeAg positive and negative CHB patients, 48-52 week of treatment with these drugs can induce a 4-7 log decrease of HBV viremia and histological improvement. Long-term suppression of active HBV replication has been found to be associated with decreased inflammation, reversal of liver fibrosis and a lower incidence of hepatocellular carcinoma. However, permanent clearance of HBV is rarely achieved with current available antiviral agents, maintenance therapy being required for continuous suppression of HBV replication. In patients on continuous therapy, drug resistant mutations develop with all four drugs. Combination therapy with different nucleos(t)ide analog drugs or nucleos(t)ide drugs and pegylated interferon needs further clinical study. Newer promising nucleotide analog drugs with more potent antiviral efficacy are also under development. PMID- 17346171 TI - Enzymes in the conversion of cholesterol into bile acids. AB - This article aims to give an overview on the characterization, properties and regulation of enzymes, particularly the cytochrome (CYP) P450 enzymes, in the formation of bile acids from cholesterol. Bile acids are biologically active molecules that promote absorption of dietary lipids in the intestine and stimulate biliary excretion of cholesterol. Bile acids and oxysterols, formed from cholesterol, act as ligands to nuclear receptors regulating the expression of important genes in cholesterol homeostasis. Thus, the bioactivation of cholesterol into bile acids is crucial for regulation of cholesterol homeostasis. The primary human bile acids, cholic acid and chenodeoxycholic acid, are formed from cholesterol via several pathways involving many different enzymes. Many of these enzymes are cytochrome P450 (CYP) enzymes, introducing a hydroxyl group in the molecule. The "classic" pathway of bile acid formation starts with a 7alpha hydroxylation of cholesterol by CYP7A1 in the liver. The "acidic" pathway starts with a hepatic or extrahepatic 27-hydroxylation by CYP27A1. There also exist some quantitatively minor pathways which may be of importance under certain conditions. Formation of cholic acid requires insertion of a 12alpha-hydroxyl group performed by CYP8B1. Oxysterols are precursors to bile acids, participate in cholesterol transport and are known to affect the expression of several genes in cholesterol homeostasis. Enzymes with capacity to form and metabolize oxysterols are present in liver and extrahepatic tissues. The enzymes, nuclear receptors and transcription factors involved in bile acid biosynthesis are potential pharmaceutical targets for the development of new drugs to control hypercholesterolemia and to prevent atherosclerosis and other diseases related to disturbed cholesterol homeostasis. The review will also discuss some inborn errors of bile acid biosynthesis and the recently acquired knowledge on the genetic defects underlying these diseases. PMID- 17346172 TI - ICAM-1 in acute myocardial infarction: a potential therapeutic target. AB - Current treatments for AMI centre on prompt restoration of epicardial coronary blood flow. Despite improvements, AMI is still associated with significant morbidity and mortality. Novel approaches are therefore keenly sought. Intercellular adhesion molecule-1 (ICAM-1, CD54) is a member of the immunoglobulin superfamily. It is implicated in neutrophil and monocyte endothelial cell adhesion, processes contributing to myocardial neutrophil infiltration and microvascular coronary slow flow, both viewed as important to the pathophysiologic responses in AMI. ICAM-1 would therefore appear an important potential therapeutic target in this context, and is the subject of this review. PMID- 17346174 TI - Chemotherapeutic strategies against Trypanosoma brucei: drug targets vs. drug targeting. AB - Trypanosoma brucei rhodesiense and T. b. gambiense are the causative agents of sleeping sickness, a fatal disease that affects 36 countries in sub-Saharan Africa. Nevertheless, only a handful of clinically useful drugs are available. These drugs suffer from severe side-effects. The situation is further aggravated by the alarming incidence of treatment failures in several sleeping sickness foci, apparently indicating the occurrence of drug-resistant trypanosomes. Because of these reasons, and since vaccination does not appear to be feasible due to the trypanosomes' ever changing coat of variable surface glycoproteins (VSGs), new drugs are needed urgently. The entry of Trypanosoma brucei into the post-genomic age raises hopes for the identification of novel kinds of drug targets and in turn new treatments for sleeping sickness. The pragmatic definition of a drug target is, a protein that is essential for the parasite and does not have homologues in the host. Such proteins are identified by comparing the predicted proteomes of T. brucei and Homo sapiens, then validated by large scale gene disruption or gene silencing experiments in trypanosomes. Once all proteins that are essential and unique to the parasite are identified, inhibitors may be found by high-throughput screening. However powerful, this functional genomics approach is going to miss a number of attractive targets. Several current, successful parasiticides attack proteins that have close homologues in the human proteome. Drugs like DFMO or pyrimethamine inhibit parasite and host enzymes alike--a therapeutic window is opened only by subtle differences in the regulation of the targets, which cannot be recognized in silico. Working against the post-genomic approach is also the fact that essential proteins tend to be more highly conserved between species than non-essential ones. Here we advocate drug targeting, i.e. uptake or activation of a drug via parasite-specific pathways, as a chemotherapeutic strategy to selectively inhibit enzymes that have equally sensitive counterparts in the host. The T. brucei purine salvage machinery offers opportunities for both metabolic and transport-based targeting: unusual nucleoside and nucleobase permeases may be exploited for selective import, salvage enzymes for selective activation of purine antimetabolites. PMID- 17346175 TI - Nucleoside transport as a potential target for chemotherapy in malaria. AB - Malaria constitutes an enormous drain on the health and economies of many countries and causes more than a million deaths annually. Moreover, resistance to existing antimalarial drugs is a growing problem, rendering the search for new targets urgent. Protozoan parasites of the genus Plasmodium that cause malaria lack the ability to synthesise the purine ring de novo and so are reliant upon salvage of purines, including hypoxanthine, inosine and adenosine, from the host. The transport systems responsible for uptake of these precursors are therefore promising targets for novel antimalarial drugs. In humans, purine uptake into many cell types is mediated by members of the Equilibrative Nucleoside Transporter (ENT) family, in particular hENT1 and hENT2. Genome sequencing has revealed that P. falciparum and P. vivax, the species responsible for the majority of malaria cases, each also possesses four members of this family, and in P. falciparum transcripts of each are expressed in the erythrocytic stages of the parasite responsible for clinical disease. One of the proteins, PfENT1, is known to be present in the parasite plasma membrane, and the kinetic properties of the heterologously expressed transporter are consistent with its representing the major purine uptake system in the trophozoite. Importantly, its inhibitor specificity and permeant selectivity differ from those of the host. In this review we discuss the possibility of exploiting these differences to develop novel antimalarial drugs that either selectively inhibit purine uptake into the pararasite or are selectively delivered by the transporter to the parasite cytoplasm. PMID- 17346176 TI - Adenosine metabolism in Toxoplasma gondii: potential targets for chemotherapy. AB - Toxoplasma gondii is an intracellular parasitic protozoan that infects approximately a billion people worldwide. Infection with T. gondii represents a major health problem for immunocompromised individuals, such as AIDS patients, organ transplant recipients, and the unborn children of infected mothers. Currently available drugs usually do not eradicate infection and as many as 50% of the patients do not respond to this therapy. Furthermore, they are ineffective against T. gondii tissue cysts. In addition, prolonged exposure to these drugs induces serious host toxicity forcing the discontinuation of the therapy. Finally, there is no effective vaccine currently available for the treatment of toxoplasmosis. Therefore, it is necessary to develop new and effective drugs for the treatment and management of toxoplasmosis. The rational design of a drug depends on the exploitation of fundamental biochemical or physiological differences between pathogens and their host. Some of the most striking differences between T. gondii and their mammalian host are found in purine metabolism. T. gondii, like most parasites studied, lack the ability to synthesize purines do novo and depend on the salvage of purines from their host to satisfy their requirements of purines. In this respect, the salvage of adenosine is the major source of purines in T. gondii. Therefore, interference with adenosine uptake and metabolism in T. gondii can be selectively detrimental to the parasite. The host cells, on the other hand, can still obtain their purine requirements by their de novo pathways. This review will focus on the broad aspects of the adenosine transport and the enzyme adenosine kinase (EC 2.7.1.20) which are the two primary routes for adenosine utilization in T. gondii, in an attempt to illustrate their potentials as targets for chemotherapy against this parasite. PMID- 17346177 TI - Purine metabolism in Mycobacterium tuberculosis as a target for drug development. AB - Tuberculosis remains a serious health problem throughout the world, and new drugs are needed to help control this disease. We have identified several purine nucleoside analogs that exhibit selective activity against Mycobacterium tuberculosis. The lead compound in this series is 2-methyl-adenosine (methyl Ado), which is active against proliferating and nonproliferating bacteria due to its ability to inhibit protein synthesis. Methyl-Ado is activated by adenosine kinase that is expressed in M. tuberculosis cells. The primary intracellular metabolite is 2-methyl-AMP, although some methyl-ATP was also produced in the cells. Adenosine kinase has been purified from M. tuberculosis cells and its biochemical activity has been characterized and compared to that of the human homolog. The gene for adenosine kinase has been determined to be Rv2202c, which had been putatively identified as a sugar kinase. Because very little is known about purine metabolism in M. tuberculosis, we have initiated studies to characterize the enzymes that are involved in salvage of purine nucleosides. We believe that enhanced knowledge of the characteristics of the enzymes involved in purine salvage in M. tuberculosis should aid in the rational design of more potent purine analogs that can selectively inhibit M. tuberculosis replication. Compounds in this class should be active against strains of M. tuberculosis that are resistant to current agents used to treat this disease and may also target latent disease. PMID- 17346178 TI - Dihydrofolate reductase as a target for chemotherapy in parasites. AB - Opportunistic infections are known to cause morbidity and mortality in immunocompromised individuals. In addition, serious infections due to several parasites are also known to affect the quality and duration of life in normal individuals. The importance of dihydrofolate reductase (DHFR) in parasitic chemotherapy arises from its function in DNA biosynthesis and cell replication. DHFR catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), an essential cofactor in the biosynthesis of thymidylate monophosphate (dTMP). Inhibition of DHFR leads to a deficiency of dTMP since DHF cannot be recycled, and thus causes inhibition of cell growth. Methotrexate (MTX) and aminopterin (AMT) were among the first known classical inhibitors of DHFR. Trimethoprim (TMP) and pyrimethamine (PYR) are among the first known non classical inhibitors of DHFR. TMP and PYR are selective but weak inhibitors of DHFR from several parasitic organisms and coadministration of sulfonamides is required to provide synergistic effects for clinical utility. Unfortunately, the side effects associated with sulfa drugs in this combination often result in cessation of therapy. Trimetrexate (TMQ) and piritrexim (PTX) are two potent non classical inhibitors, neither of which exhibit selectivity for pathogen DHFR and must be used with host rescue. However, the current combination therapy suffers from high cost, in addition, several mutations have been reported in the active site of parasitic DHFR rendering the infections refractive to known DHFR inhibitors. The selectivity of TMP is a hallmark in the development of DHFR inhibitors and several efforts have been made to combine the potency of PTX and TMQ with the selectivity of TMP. Thus the structural requirements for DHFR inhibition are of critical importance in the design of antifolates for parasitic chemotherapy. Structural requirements for inhibition have been studied extensively and novel agents that exploit the differences in the active site of human and parasitic DHFR have been proposed. This review discusses the synthesis and structural requirements for selective DHFR inhibition and their relevance to parasitic chemotherapy, since 1995. PMID- 17346179 TI - Invasion and egress by the obligate intracellular parasite Toxoplasma gondii: potential targets for the development of new antiparasitic drugs. AB - Intracellular protozoan parasites are a great threat to animal and human health. To successfully disseminate through an organism these parasites must be able to enter and exit host cells efficiently and rapidly. The inhibition of invasion or egress of obligate intracellular parasites is regarded as a goal for drug development since these processes are essential for their survival and likely to require proteins unique to the parasites. Thus, a more comprehensive knowledge of invasion and egress proteins will aid in the development of drugs and vaccines against these intracellular pathogens. In recent years, the study of a particular parasite, Toxoplasma gondii, has yielded valuable information on how invasion and egress are achieved by some protozoan parasites. Besides being a good model system for the study of parasite biology, Toxoplasma is an important human pathogen capable of causing devastating disease in both immunocompromised individuals and developing fetuses. The lack of effective, inexpensive and tolerable drugs against Toxoplasma makes the development of new therapies an imperative. The following review describes how the identification and in depth study, using proteomics, forward genetics and pharmacology of the Toxoplasma proteins involved in entering and exiting human cells provide an important starting point in identifying targets for drug discovery. PMID- 17346180 TI - The manzamines as an example of the unique structural classes available for the discovery and optimization of infectious disease controls based on marine natural products. AB - Natural products have served humankind as drug leads for thousands of years. In the last century natural products have not only served as drugs but have inspired the generation of countless synthetic drugs and drug-leads around natural product pharmacophores. There are no disease targets for which natural products have played a more significant role than in the case of malaria and other parasitic diseases. In this review the significance of the manzamine class of marine alkaloids is presented as an example of the future utility of the oceans in the development of antiparasitics. The manzamines represent one of the few new structural classes identified in recent decades with potential for the control of malaria and tuberculosis. While considerable work remains to successfully optimize this class of drug-leads the novel pharmacophore and significant metabolic stability combined with a rapid onset of action and long half-life all strongly support further investigations of this group of potential drug candidates. PMID- 17346182 TI - The IGF-I signaling pathway. AB - The insulin-like growth factor (IGF)-I is implicated in the regulation of protein turnover and exerts potent mitogenic and differentiating effects on most cell types. IGF-I biological actions are mediated by the IGF-I receptor, comprised of two extra-cellular alpha-subunits, containing hormone binding sites, and two membrane-spanning beta-subunits, encoding an intracellular tyrosine kinase. Hormone binding activates the receptor kinase, leading to receptor autophosphorylation and tyrosine phosphorylation of multiple substrates, including the IRS and Shc proteins. Through these initial tyrosine phosphorylation reactions, IGF-I signals are transduced to a complex network of intracellular lipid and serine/threonine kinases that are ultimately responsible for cell proliferation, modulation of tissue differentiation, and protection from apoptosis. This review will focus on the IGF-I receptor structure and function, its intracellular signaling pathways, and some important implications of the activation of the IGF-I signal transduction system in specific tissues. PMID- 17346183 TI - The role of insulin receptor isoforms and hybrid insulin/IGF-I receptors in human cancer. AB - This review will focus on the emerging role of the insulin receptor (IR) in cancer. Several epidemiological studies have shown that insulin resistance states, characterized by hyperinsulinemia, are associated with an increased risk for a number of malignancies, including carcinomas of the breast, prostate, colon and kidney. Recent data have elucidated some molecular mechanisms by which IR is involved in cancer. First, IR is overexpressed in several human malignancies. Interestingly, one of the two IR isoform (IR-A) is especially overexpressed in cancer. IR-A is the IR fetal isoform and has the peculiar characteristic to bind not only insulin but also IGF-II. Second, IR forms hybrid receptors with the homologous IGF-IR, which is also commonly overexpressed in cancer. These hybrid receptors containing IR-A hemidimers have broad binding specificity as they bind IGF-I and also IGF-II and insulin. By binding to hybrid receptors, insulin may stimulate specific IGF-IR signaling pathways. Overexpression of IR-A is, therefore, a major mechanism of IGF system overactivation in cancer. These findings may have important implications for both the prevention and treatment of common human malignancies. They underline the concept that hyperinsulinemia, associated with insulin resistance and obesity, should be treated by changes in life style and/or pharmachological approaches to avoid an increased risk for cancer. IR-A isoform and hybrid receptors should be regarded, therefore, as potential molecular targets for novel anti-cancer therapies. PMID- 17346184 TI - Anti-apoptotic actions of insulin-like growth factors: lessons from development and implications in neoplastic cell transformation. AB - Insulin-like growth factor-I (IGF-I) is widely expressed during development, and is actively involved in the regulation of cell growth, proliferation, and differentiation. Underlying these activities is the capacity of IGF-I to promote survival in a variety of cell types, including those of the nervous system. However, in adult tissues deregulation of the IGF system can cause undesired cell survival and therefore excessive cell proliferation. Here, we review the contribution of IGF-I in developmental processes with a focus on the development of the inner ear, as well as pathological implications resulting from IGF-I deregulation during cancer. PMID- 17346185 TI - Crosstalk between IGF signaling and steroid hormone receptors in breast cancer. AB - Breast cancer development and progression is regulated by crosstalk between steroid hormones (SHs) (e.g., estrogens, progestins and androgens) and growth factors such as insulin-like growth factors (IGFs), insulin, epidermal growth factors (EGFs), transforming growth factors, and vascular endothelial growth factor. The biological effects of SHs are mediated by the nuclear receptors acting as transcriptional activators. Steroid hormone receptors (SRs), in addition to being induced by their own ligands, are also regulated by cellular kinases activated by growth factors. Growth factors are known to influence the expression and activity of SRs as well as regulate the action of various SR transcriptional co-factors. In turn, the expression of growth factor receptors, their ligands, and signaling molecules is often controlled by SHs. This review will focus on crosstalk between the IGF-I system and several SRs implicated in breast cancer. PMID- 17346186 TI - The IGF axis in prostate cancer. AB - Prostate cancer, the most frequent non-cutaneous malignancy in men from industrialized countries, is a growing medical problem, representing the second leading cause of male cancer deaths. In the last decade, converging evidence from epidemiological and biological studies suggests that the Insulin-like Growth Factor (IGF) axis is involved in the tumorigenesis and neoplastic growth of prostate cancer. Epidemiological observations indicated that circulating IGF-I levels are positively associated with the increased risk of prostate cancer. The activation of type I IGF receptor (IGF-IR) by IGF-I and/or IGF-II, has mitogenic and antiapoptotic effects on normal and malignant prostate cells. Altered expression of IGF axis components has also been reported in vitro and in animal models of prostate cancer, as well as in human prostate cancer tissue samples. In this review we address and analyze epidemiological studies, in vitro and in vivo cancer models, and human ex vivo prostate cancer researches performed to date supporting the role of IGF axis in prostate cancer. PMID- 17346187 TI - The IGF-I axis in thyroid carcinoma. AB - Insulin like-growth factor I (IGF-I) has been involved in the pathogenesis of a variety of human neoplasia due to the mitogenic and anti-apoptotic properties of its cognate receptor. In human thyroid carcinomas, we have previously documented an increased immunoreactivity of both IGF-I and the IGF-I receptor (IGF-I R) associated with up regulation of IGF-I mRNA . Immunoreactivity of IGF-I and cognate receptor positively correlated with tumor diameter and wide intrathyroidal extension but not with patient's gender and age or with the stage of the tumors and the occurrence of limph node metastases. Most experimental studies indicate that the effects of IGF-I on target cells are regulated in a complex fashion and depend on the simultaneous occurrence of IGF-IR and the binding proteins. PMID- 17346188 TI - Anti-tumor activity of non-nucleosidic reverse transcriptase inhibitors. AB - Reverse Transcriptase (RT) activity is historically associated with the replication of infectious retroviruses. Cellular RT-coding genes have subsequently been identified in eukaryotic genomes. These genes are harbored within retrotransposable elements (retrotransposons and endogenous retroviruses), mobile DNA sequences characterized by the ability to integrate in mammalian genomes through RNA intermediates. Retrotransposition is mediated by an RT activity that catalyzes the reverse transcription of RNA into cDNA copies. A vast body of correlative evidence links up-regulated RT activity to cell systems with a high proliferative potential and low differentiation level, including embryonic tissues and tumors. In contrast, RT is silenced, or expressed at low levels, in differentiated cells. In recent work, we have used non-nucleosidic RT inhibitors widely employed to treat HIV infection and we have observed that these molecules exert a powerful cytostatic and differentiating activity in several models of human cancers both in vitro and in vivo, associated with the inhibition of endogenous RT activity. This review addresses the potential role of RT inhibitors as new anticancer therapeutic drugs. Based on preclinical observations, we also discuss the working hypothesis that the differentiating activity of RT inhibitors may re-establish or improve the efficacy of conventional treatments in specific conditions, such as hormone-refractory prostate carcinoma, anaplastic thyroid tumors and hematological malignancies. These novel findings strongly support the need for clinical trials to test the anti-tumor activity of RT inhibitors in specific malignancies. PMID- 17346189 TI - Pancreatic islets under attack: cellular and molecular effectors. AB - Abundant information is available on the involvement of various cellular and molecular mechanisms in beta cell apoptosis. The experimental evidence is controversial and difficult to reconcile, and the mechanisms of evasion of the autoreactive clones from immune surveillance are poorly understood. Multiple apoptotic pathways play a role in destructive insulitis, including perforin/granzyme, Fas/Fas-ligand (FasL), and other members of the necrosis factor superfamily. These pathways present redundant behaviors in both the initial and late stages of beta cell injury, and at the same time, each molecular mechanism is dispensable in the evolution of autoimmune diabetes. There may be a preferential use of perforin/granzyme in CD8(+) T cell-mediated lysis, which participates in onset of autoimmunity, and a predominance of FasL in CD4(+) T cell-mediated insulitis. Several cytokines released in the inflammatory infiltrate induce Fas expression in beta cells, priming them to FasL-mediated apoptosis. In this review, we focus on the possible participation of multiple cell subsets and molecular mechanisms in the pathogenesis of diabetes to the point where inflammation incites an irreversible vicious cycle that perpetuates beta cell death. PMID- 17346190 TI - Drug carriers in pharmaceutical design: promises and progress. AB - Ever since pure molecular entities have been adapted as drug, varied manifestations other than elimination of infections are frequently been acknowledged as side effects. Contemporary drug research focuses on these issues besides developing new molecules for the restoration of unnatural functional deviations in various tissues and organs. The most promising advancement to achieve this concept of ideal drug is the encapsulation of drug in biocompatible nano or microspheres. Encapsulation can insulate the toxic drugs and lease a better half life to molecules undergoing spontaneous degradation under physiological conditions. It is also worthwhile to incorporate along some immunomodulators to strengthen and channelize the innate immune response of the host in right direction. This holistic approach would also prevent the physiological modulations dictated by invading pathogens, which paralyze the important functionaries of the host. Lipoproteins, lipid like molecules and probiotic non-colonizing bacterial membrane mimics might prove to be the best ingredients for encapsulation. Some synthetic non-immunogenic supra molecules like fullarenes and dendrimers also exhibit great potential for the development of new encapsulation technology. Here an attempt is made to review the progress in terms of aims and achievements in the area of drug carriers and encapsulation with its overall impact on therapeutic industry. PMID- 17346192 TI - New tuberculosis drugs in development. AB - Over the past 50 years, no new drug classes have been introduced to treat tuberculosis. Tuberculosis (TB) kills nearly two million people a year mainly in the poorest communities in the developing world. It afflicts millions more. About one third of the world's population is silently infected with TB that may erupt into disease with increased age or suppression of the immune system. Nearly nine million new active cases develop every year. The World Health Organization (WHO) declared the disease a global emergency as long ago as 1993. Although huge efforts in public health control have reduced the disease burden within most established market economies, in Africa and Asia the epidemic continues to accelerate, particularly fueled by the HIV epidemic. Furthermore, resistance to the standard drugs isoniazid and rifampicin is increasing worldwide. Since the 1990s, mycobacteria have emerged with resistance patterns rendering all currently available antibiotics ineffectual. The pharmaceutical industry has mostly abandoned TB drug development due to perceived non-profitable consumer market and the diminishing number of companies engaged in anti-infective research. The public sector and infectious disease researchers have responded to advance fundamental science and to create new chemical entities as early drug candidates. With support from research funding agencies, philanthropic donors, and the STOP TB Partnership, new chemical tools and new approaches to effectively implement TB control programs are evolving. Advanced preclinical development and strategies for Phase III clinical trials remain gap areas that will require additional engagement from all sectors. PMID- 17346193 TI - The cell-wall core of Mycobacterium tuberculosis in the context of drug discovery. AB - Present-day understanding of the architecture of the entire cell-wall of Mycobacterium tuberculosis amounts to a "core" template comprised of peptidoglycan with phosphodiester linkage, via a linker disaccharide, to a linear D-galactofuran, to which, in turn, are attached several strands of a highly branched D-arabinofuran. The cell-wall mycolic acids are linked via an ester to the majority of the non-reducing termini of the D-arabinan. The mycolic acids are oriented perpendicular to the plane of the membrane and provide a truly special lipid barrier responsible for many of the physiological and disease-inducing aspects of M. tuberculosis. Intercalated within this environment are the phthiocerol dimycocerosates, cord factor or dimycolyltrehalose, sulfolipids, phosphatidylinositol mannosides and the related lipomannan and lipoarabinomannan, etc., agents responsible for much of the pathogenesis of tuberculosis. Interest in the biosynthesis of the cell-wall core, regarded, unlike the ancillary lipids, as essential to bacterial viability and integrity, is now driven by the pressing need for alternative drugs to counteract drug-resistant tuberculosis. In a manner analogous to the roles of lipid I and II in peptidglycan formation, synthesis of the entire arabinogalactan is initiated by transferring activated sugars to decaprenyl-phosphate, giving rise to the linker disaccharide, followed by stepwise elongation of the galactan, and the arabinan, apparently one sugar at a time. The genetics and enzymology of these polymerization events have not been well defined, nor have the final steps, namely the attachment of mycolic acids and ligation to peptidoglycan. However, what is known of the earlier events in cell-wall core synthesis has attracted interest in terms of new anti-tuberculosis drug development. PMID- 17346194 TI - Development of modern InhA inhibitors to combat drug resistant strains of Mycobacterium tuberculosis. AB - Strategies for the development of novel tuberculosis chemotherapeutics against existing drug resistant strains involve the identification and inhibition of novel drug targets as well as the design and synthesis of compounds against historical targets. InhA, the enoyl reductase from the mycobacterial type II fatty acid biosynthesis pathway, is a target of the frontline chemotherapeutic, isoniazid (INH). Importantly, the majority of INH-resistant clinical isolates arise from mutations in KatG, the enzyme responsible for activating isoniazid, into its active form. Thus compounds that inhibit InhA without first requiring KatG activation will be active against the majority of INH resistant strains of Mycobacterium tuberculosis. This review describes the role of InhA in cell wall biosynthesis and recent progress in the development of novel diphenyl ether-based InhA inhibitors that have activity against both sensitive and drug resistant strains of M. tuberculosis. PMID- 17346195 TI - Screening for novel antituberculosis agents that are effective against multidrug resistant tuberculosis. AB - The challenges in preventing and controlling tuberculosis are further complicated by the deadly rise of multi-drug-resistant tuberculosis (MDR-TB). Recognizing the seriousness of the situation, we initiated a program to screen new agents that would satisfy these unmet needs and have a favorable safety profile. Mycobacteria are well known for their lipid-rich properties. In Mycobacterium tuberculosis, mycolic acid in particular has been established the wall component related to the pathogenesis in the host. There are approximately 250 identified genes related to biosynthesis of the lipid turnover that contain InhA, the main target of isoniazid. Thus, the logical approach for developing a chemotherapy agent against tubercle bacilli included screening compounds that could inhibit the biosyntheses of mycolic acid and that had a novel chemical structure to ensure improved efficacy against MDR-TB. Some of the screening systems established for those purposes and some of the candidates are outlined. PMID- 17346196 TI - Nitrofurans as novel anti-tuberculosis agents: identification, development and evaluation. AB - During a search for new anti-tuberculosis agents, a screen of a commercially available library provided a hit nitrofuranyl amide. This hit was selected for further development due to its potential as an anti-tuberculosis agent with a novel mechanism of action, and its potential for activity against both actively growing and latent bacteria. This review covers the optimization of this lead and the strategies applied for developing this series into anti-tuberculosis agents. To optimize the hit, a series of libraries were synthesized, producing several compounds that showed increased anti-tuberculosis activity along with a strong structure activity relationship. The most active compounds from the first optimization series showed good in vitro anti-tuberculosis activity and limited in vivo efficacy, but their application was restricted due to solubility problems. Therefore, a second generation optimization library was designed and synthesized in order to increase bioavailability and solubility while maintaining good anti-tuberculosis activity. Hydrophilic cyclic secondary amines were substituted to the core scaffold and a benzyl piperazine substitution was found to be most effective in achieving improved solubility and potent anti tuberculosis activity. However, bioactivity studies of these 2nd generation leads showed that the in vivo anti-tuberculosis activity of these compounds was limited due to rapid metabolism. Consequently, a 3rd generation of compounds was designed and synthesized in which potential sites of metabolism were blocked. PMID- 17346197 TI - FtsZ: a novel target for tuberculosis drug discovery. AB - The emergence of multi-drug resistant Mycobacterium tuberculosis (Mtb) strains has made many of the currently available anti-TB drugs ineffective. Accordingly there is a pressing need to identify new drug targets. FtsZ, a bacterial tubulin homologue, is an essential cell division protein that polymerizes in a GTP dependent manner, forming a highly dynamic cytokinetic ring, designated as the Z ring, at the septum site. Following recruitment of other cell division proteins, the Z ring contracts, resulting in closure of the septum and then formation of two daughter cells. Since inactivation of FtsZ or alteration of FtsZ assembly results in the inhibition of Z ring and septum formation, FtsZ is a very promising target for new antimicrobial drug development. This review describes the function and dynamic behaviors of FtsZ, its homology to tubulin, and recent development of FtsZ inhibitors as potential anti-TB agents. PMID- 17346198 TI - Does calprotectin represent a regulatory factor in host defense or a drug target in inflammatory disease? AB - Calprotectin, a protein composed by two subunits of 8 and 14 kD respectively, is released by neutrophils in the biological fluids under inflammatory states. For instance, detection of calprotectin in faeces represents a diagnostic tool in the case of inflammatory bowel disease. Quite interestingly, calprotectin is increased in the stool of healthy newborns from day three up to day thirty and, physiologically, this increase may be interpreted as a defense mechanism against yeast and fungi. Therapeutic attempts at inhibiting the deleterious effect of calprotectin have been experimentally made by using lycoricinidol. This natural compound is able to hamper the calprotectin-induced apoptosis on the one hand. On the other hand, the same compound plays a prophylactic role in the course of experimental arthritis in rats. PMID- 17346199 TI - Chemokines as drug targets in type 1 diabetes. AB - Acute or chronic inflammation is thought to play a major role in the etiology and/or pathogenesis of autoimmune disease. Often viral infections are the initial cause for a local inflammatory reaction resulting in tissue infiltration by activated leukocytes. The activation and trafficking of these leukocytes to the site of inflammation is conducted by chemoattractant cytokines, termed chemokines. Depending on the genetic background and the history of previous infections, such infiltrating leukocytes can potentially include autoaggressive lymphocytes with specificity to tissue antigens. The number of specific precursor lymphocytes, strength of activation and degree of counteracting immunoregulatory measures determine whether such an autoimmune incident ultimately results in autoimmune disease. Thus, by blocking the initial inflammatory insult one could in theory prevent the excessive attraction of autoaggressive lymphocytes to the inflammation site and the subsequent formation of a pattern that leads to autoimmune disease. This review focuses on blocking of chemokines in animal models of type 1 diabetes and discusses the possible applications of such treatments in human autoimmune disease. PMID- 17346200 TI - Epigenetic alterations of the Wnt/beta-catenin pathway in human disease. AB - The Wnt/beta-catenin pathway plays critical roles in cell physiology, including determination, proliferation, migration and differentiation in embryonic development and adult homeostasis. Several components of the Wnt/beta-catenin pathway, such as SFRPs, WIF-1, DKK-1, APC, AXIN2, ICAT, LEF1 and beta-catenin, are the target of mutations or epigenetic inactivation leading to the deregulation or constitutive activation of the Wnt/beta-catenin pathway. Aberrant activation of the Wnt signalling pathway abrogates controlled growth and impairs cell differentiation. Alterations of the Wnt signalling pathway have been found in cancer, osteoporosis, ischemic neuronal death and other human diseases. Here we review the alterations of the Wnt/beta-catenin signalling cascade and discuss the biological significance and relationship between mutation and/or epigenetic silencing within the same pathway. PMID- 17346201 TI - CD40L - a multipotent molecule for tumor therapy. AB - CD40L-based therapy is currently under intensive investigation for its potent anti-tumor effects in experimental animal models of cancer as well as in Phase I clinical trials. CD40L is one of the strongest inducers of Th1 responses although it stimulates both innate and adaptive immunity. The molecule is normally expressed by activated immune cells such as T helper cells that act on dendritic cells to induce their maturation and capability of activating tumor-reactive T cells. Moreover, recent findings implicate that CD40L stimulation abrogates the suppressive effect of T regulatory cells. Interestingly, while being an activator of immune cells, CD40L has been shown to directly induce apoptosis in tumor cells by mechanisms only beginning to emerge. These two major effector mechanisms synergize to combat tumor growth. Optimal use of this multipotent molecule might therefore result in effective immunotherapy of cancer. CD40L can be administered to patients as soluble protein trimers. To achieve membrane-bound expression, viral vectors can be used to transfer CD40L cDNA into 1) tumor cells ex vivo for creating CD40L-expressing tumor vaccines, 2) ex vivo cultured dendritic cells for cell therapy, and 3) tumor nodules in situ. CD40L substitutes such as CD40 directed agonistic antibodies have been evaluated with interesting results in experimental models. In this survey, different types and mechanisms of CD40L based therapy will be discussed from bench to bedside. PMID- 17346202 TI - Use of systemic proteasome inhibition as an immune-modulating agent in disease. AB - Bortezomib is the first proteasome inhibitor to be used clinically for the treatment of multiple myeloma and has been suggested as a possible treatment for a wide variety of hematologic and solid malignancies. Recent data suggests that potent immunomodulatory effects can also occur with systemic proteasome inhibition. This has been recently shown to occur in a graft-versus host disease model following bone marrow transplantation in mice. The suggested direct immunological effects of bortezomib treatment to include a decrease in anti apoptotic protein levels, an increase in expression of TNF-family receptors (specifically Apo2L/TRAIL), induction of apoptosis, and inhibition of the transcription factor NF-kappaB. The NF-kappaB pathway has been associated with the regulation of numerous immune and inflammatory response mediators. In this review, we will present recent information concerning the potential therapeutic implications of bortezomib for a range of immune disorders. These findings would suggest that bortezomib treatment may be of clinical significance to suppress solid organ transplant rejection, autoreactive T cell responses, pro-inflammatory cytokine production, and consequently disease progression and pathology in autoimmunity. PMID- 17346203 TI - Immunotherapeutic approaches in MS: update on pathophysiology and emerging agents or strategies 2006. AB - Multiple sclerosis (MS) is a chronic disabling disease with significant implications for patients and society. The individual disease course is difficult to predict due to the heterogeneity of clinical presentation as well as radiological and pathological findings. Although its etiology still remains unknown, the last decade has generated considerable success in understanding the underlying pathophysiology of MS. In addition to its view as a prototypic inflammatory autoimmune disorder, recent data support the importance of primary and secondary neurodegenerative mechanisms such as oligodendrocyte death, axonal loss and ion channel dysfunction. The deepened understanding of the immunopathogenesis as well as the limited effectiveness of the currently approved disease modifying therapies have led to a tremendous number of trials investigating potentially new drug targets. Emerging treatments take into account the different immunopathological mechanisms as well as strategies to protect against axonal damage or to promote remyelination. This review provides a compilation of novel immunotherapeutic strategies or new aspects of known immunotherapeutic agents which have evolved recently. The pathogenetic rationale of these novel drug targets for the treatment of MS as well as accompanying preclinical and clinical data are highlighted. PMID- 17346204 TI - Role of insulin in the pathogenesis of free fatty acid-induced insulin resistance in skeletal muscle. AB - Insulin resistance is a pathophysiological link of obesity to type 2 diabetes. The initial cause of insulin resistance is critical for prevention and treatment of type 2 diabetes. Lipotoxicity is a well-known concept in the explanation of initiation of insulin resistance. Although there are several prevailing hypotheses about the cellular/molecular mechanisms of lipotoxicity, such as inflammation, oxidative stress, hyperinsulinemia, and ER stress, the relative importance of these hypothesized events remains to be determined. The role of hyperinsulinemia is relatively under documented in the literature for the initiation of insulin resistance. In this review, an interaction of fatty acid and beta-cells, and a synergy between free fatty acids (FFAs) and insulin are emphasized for the role of hyperinsulinemia. This article presents the evidence about FFA-induced insulin secretion in vitro and in vivo, recent advances in the molecular mechanism of FFA action in beta-cells, a role of GPR40 in the development of insulin resistance, and the negative feedback loop of the insulin receptor signal pathway. The negative feedback loop is discussed in detail with a focus on IRS-1 serine kinases. This article provides a substantial support for the role of insulin in the early stages of FFA-associated insulin resistance. The hypothesis of insulin's role in lipotoxicity is referred to as the "insulin hypothesis" in this review. According to this hypothesis, prevention of increased beta-cell response to glucose may be a potential approach for early intervention of metabolic syndrome. PMID- 17346206 TI - Exploring DNA topoisomerases as targets of novel therapeutic agents in the treatment of infectious diseases. AB - DNA topoisomerases are ubiquitous enzymes needed to overcome topological problems encountered during DNA replication, transcription, recombination and maintenance of genomic stability. They have proved to be valuable targets for therapy, in part because some anti-topoisomerase agents act as poisons. Bacterial DNA gyrase and topoisomerase IV (type IIA topoisomerases) are targets of fluoroquinolones while human topoisomerase I (a type IB topoisomerase) and topoisomerase II are targets of various anticancer drugs. Bacterial type IA topoisomerase share little sequence homology to type IB or type IIA topoisomerases, but all topoisomerases have the potential of having the covalent phosphotyrosine DNA cleavage intermediate trapped by drug action. Recent studies have demonstrated that stabilization of the covalent complex formed by bacterial topoisomerase I and cleaved DNA can lead to bacterial cell death, supporting bacterial topoisomerase I as a promising target for the development of novel antibiotics. For current antibacterial therapy, the prevalence of fluoroquinolone-resistant bacterial pathogens has become a major public health concern, and efforts are directed towards identifying novel inhibitors of bacterial type IIA topoisomerases that are not affected by fluoroquinolone resistant mutations on the gyrase or topoisomerase IV genes. For anti-viral therapy, poxviruses encode their own type IB topoisomerases; these enzymes differ in drug sensitivity from human topoisomerase I. To confront potential threat of small pox as a weapon in terrorist attacks, vaccinia virus topoisomerase I has been targeted for discovery of anti-viral agents. These new developments of DNA topoisomerases as targets of novel therapeutic agents being reviewed here represent excellent opportunities for drug discovery in the treatment of infectious diseases. PMID- 17346207 TI - Novel targets for the development of anti-herpes compounds. AB - Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are members of the Herpesviridae family. HSV infections have been known since ancient times and are one of the most common communicable diseases in humans. Although infections are often subclinical, HSV can cause mild to severe diseases, especially in immunocompromised patients. Herpes simplex viruses establish latency in the nuclei of neuronal cells and may reactivate, with or without symptoms, throughout the host's lifetime. Over one third of the world's population suffer from recurrent HSV infections several times a year and are thus capable of transmitting HSV by close personal contact. There are few drugs licensed for the treatment of HSV infections. Most target the viral DNA polymerase, and indeed acyclovir remains the reference treatment some thirty years after its discovery! Extensive clinical use of this drug has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the crucial need for the development of new anti-herpes drugs that can inhibit infection by both wild-type viruses and drug-resistant strains. Over the last few years, significant efforts have been made to set up a range of strategies for the identification of potential new anti-viral drugs. One alternative is to develop drugs with different mechanisms of action. The present article reviews potential viral and cellular targets that are now known to be involved in HSV infection and for which specific inhibitors with anti-HSV activity, at least in cell culture, have been identified. PMID- 17346208 TI - Targeting bacterial secretion systems: benefits of disarmament in the microcosm. AB - Secretion systems are used by many bacterial pathogens for the delivery of virulence factors to the extracellular space or directly into host cells. They are attractive targets for the development of novel anti-virulence drugs as their inactivation would lead to pathogen attenuation or avirulence, followed by clearance of the bacteria by the immune system. This review will present the state of knowledge on the assembly and function of type II, type III and type IV secretion systems in Gram-negative bacteria focusing on insights provided by structural analyses of several key components. The suitability of transcription factors regulating the expression of secretion system components and of ATPases, lytic transglycosylases and protein assembly factors as drug targets will be discussed. Recent progress using innovative in vivo as well as in vitro screening strategies led to a first set of secretion system inhibitors with potential for further development as anti-infectives. The discovery of such inhibitors offers exciting and innovative opportunities to further develop these anti-virulence drugs into monotherapy or in combination with classical antibiotics. Bacterial growth per se would not be inhibited by such drugs so that the selection for mutations causing resistance could be reduced. Secretion system inhibitors may therefore avoid many of the problems associated with classical antibiotics and may constitute a valuable addition to our arsenal for the treatment of bacterial infections. PMID- 17346209 TI - Recent developments in the virology and antiviral research of severe acute respiratory syndrome coronavirus. AB - This article summarizes the significant developments and new discoveries in both the virology and antiviral research associated with the severe acute respiratory syndrome coronavirus (SARS CoV) that were reported in 2005 and 2006. Areas reviewed include genomic studies and the identification of bat-SARS CoV, spike protein and host cell entry, nucleocapsid protein, accessory proteins, non structural proteins of the replicase complex, viral proteases and their inhibitors, and clinical treatment of SARS with ribavirin. PMID- 17346210 TI - Antibiotic resistance during therapy: mechanisms and means of control. AB - Antibiotic resistance is a serious public health problem. The most effective way to control this phenomenon is to make rational use of antibiotics. However, antibiotic resistance is a complex process in which clinical, pharmacodynamic, pharmacokinetic and microbiological factors all play a part. Since antibiotic therapy is usually performed empirically, clinicians should follow guidelines that take all these factors into account together with the concepts of evidence based medicine. These guidelines may be elaborated using information technology tools that help to collect, analyze and weigh up all the information available on a certain pathogen. Therefore, the administration of antibiotics should be controlled with the help of multi-disciplinary working groups and in accordance with objective data collected following a thorough analysis of all the available information. PMID- 17346211 TI - Strategies to design inhibitors of Clostridium botulinum neurotoxins. AB - Botulinum neurotoxins (BoNTs), produced by spore-forming anaerobic Clostridium botulinum, are the most toxic substances known. They cause the life-threatening disease botulism, characterized by flaccid muscle paralysis. While the natural cases of botulism are rare, due to their extreme toxicity and easy production, BoNTs have become potential biowarfare agents, and create maximum fear among populations concerned with bioterror agents. The only available antidote against BoNTs is equine antitoxin. Equine antitoxin can only target the toxins at extracellular level, and can not reverse the paralysis caused by botulism. In addition, equine antibody can cause severe hypersensitivity reactions, and is limited to be used for prophylaxis treatment. BoNTs are large proteins with three distinct domains, the binding domain, the translocation domain, and the enzymatic domain with highly specific endopeptidase activity to cleave the proteins involved the neurotransmitter release. Targeting any of these domains can inhibit the functions of BoNT. Humanized monoclonal antibodies, small peptides and peptide mimetics, receptor mimics, and small molecules targeting the endopeptidase activity have emerged as potential new inhibitors against BoNTs. With the structure of BoNT resolved, molecular modeling and rational design of potent antidotes against botulism is on the horizon. An area that has not been explored for designing the antidotes against botulism is aptamers, which have been successfully developed as therapeutics in several areas. This review will focus on some of these new strategies to design effective antidotes against botulism. The strategies reviewed in this article can be easily applied to design inhibitors for other bacterial toxins. PMID- 17346212 TI - Antiviral strategies against human coronaviruses. AB - Since the mid 60's the human coronaviruses (HCoV), represented by HCoV-OC43 and HCoV-229E, were generally considered relatively harmless viruses. This status changed dramatically with the emergence of SARS-CoV in 2002/2003. The SARS-CoV pandemic took 774 lives around the globe and infected more than 8000 people in 29 countries. SARS-CoV is believed to be of zoonotic origin, transmitted from its natural reservoir in bats through several animal species (e.g., civet cats, raccoon dogs sold for human consumption in markets in southern China). The epidemic was halted in 2003 by a highly effective global public health response, and SARS-CoV is currently not circulating in humans. The outbreak of SARS-CoV and the danger of its re-introduction into the human population, as well as the danger of the emergence of other zoonotic coronaviral infections triggered an intense survey for an efficient treatment that resulted in the evaluation of several anticoronaviral compounds. HCoV-NL63 and HCoV-HKU1 were identified shortly after the SARS-CoV outbreak. The 4 human coronaviruses HCoV-229E, HCoV OC43, HCoV-NL63 and HCoV-HKU1 cause mild respiratory illnesses when compared to SARS, but these infections are involved in 10 - 20 % of hospitalizations of young children and immunocompromised adults with respiratory tract illness. Therefore, there is an urgent need for a successful therapy to prevent disease induction or a vaccine to prevent new infections. This review summarizes the current status of anticoronaviral strategies. PMID- 17346213 TI - Human defensins: turning defense into offense? AB - Defensins are a family of antimicrobial cationic peptides that act as a rapid response force against microbial invasion in a wide range of organisms, including plants, insects, animals and humans. In humans, defensins are produced predominantly by leukocytes and epithelial cells and are an important factor of innate immunity. In addition to their major role as natural antibiotics, defensins are increasingly recognized as signaling molecules in adaptive immunity and aberrant defensin expression has been associated with infectious diseases. In this review, we discuss the role of human defensins in relation to infectious disease and the possibility of novel defensin-based therapeutic approaches. PMID- 17346214 TI - Somatostatin sst4 ligands: chemistry and pharmacology. AB - Several classes of compounds (thioureas, ureas, beta-glucosides, sulfonamides, and cyclic peptides) show enhanced binding affinity and selectivity at somatostatin subtype 4 receptors (sst4). Pharmacophore models have recently been proposed to explain receptor subtype selectivity. The chemistry and therapeutic potential of sst4 ligands will be the subject of this review. PMID- 17346215 TI - Recent advances in the development of hybrid molecules/designed multiple compounds with antiamnesic properties. AB - Novel compounds have been developed that (in many cases) inhibit cholinesterases and concomitantly interact with at least one further pharmacological target, such as 5-HT3 or H3 receptors. But also enzymes like monoamine oxidase and the serotonin transporter have been targeted. Hybrid molecules can also incorporate antioxidant or neuronal Ca2+-channel-blocking structures. PMID- 17346216 TI - Radioactive drugs in drug development research: quality assurance issues. AB - Increasing number of new drugs, drug formulations and drug delivery systems is evaluated using noninvasive imaging methods. A successful use of new drugs and radiopharmaceuticals depends on their proven quality. This review provides a brief outline of the quality control procedures required for radiolabeled drugs within the context of the existing regulations. PMID- 17346217 TI - G-coupled protein receptors and breast cancer progression: potential drug targets. AB - Breast cancer remains a leading cause of death despite early screening and advances in medicine. Bone marrow metastasis often complicates the clinical picture by requiring more aggressive treatment and worsening long-term prognoses. Recent therapeutic targeting of hormonal receptors such as human epidermal growth factor receptor 2 and estrogen receptor has shown limited success in treating localized disease for those patients whose cancer cells are responsive. Although traditional approaches such as chemotherapy have demonstrated many successes, these agents fail to target quiescent cancer stem cells, which might have entered the bone marrow where they might be responsible for the quiescence population. Following years of clinical remission, these dormant cells could lead to secondary cancer resurgence. To date, little progress has been made in the development of targeted treatments for receptor negative and metastatic disease. In this review, we discuss the role of G-protein coupled receptors, including neurokinin-1, neurokinin-2 and chemokine receptor 4, as novel targets in the treatment of breast cancer. PMID- 17346218 TI - CD26/dipeptidyl peptidase IV as a novel therapeutic target for cancer and immune disorders. AB - CD26 is a 110 kDa surface glycoprotein with intrinsic dipeptidyl peptidase IV (DPPIV) activity that is expressed on numerous cell types and has a multitude of biological functions. An important aspect of CD26 biology is its peptidase activity and its functional and physical association with molecules with key roles in various cellular pathways and biological programs. CD26 role in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in T-lymphocyte activation as well as antigen presenting cell-T-cell interaction. Recent work also suggests that CD26 has a significant role in tumor biology, being both a marker of disease behavior clinically as well as playing an important role in tumor pathogenesis and development. In this paper, we will review emerging data that suggest CD26 may be an appropriate therapeutic target for the treatment of selected neoplasms and immune disorders. Through the use of various experimental approaches and agents to influence CD26/DPPIV expression and activity, such as anti-CD26 antibodies, CD26/DPPIV chemical inhibitors, siRNAs to inhibit CD26 expression, overexpressing CD26 transfectants and soluble CD26 molecules, our group has shown that CD26 interacts with structures with essential cellular functions. Its association with such key molecules as topoisomerase IIalpha, p38 MAPK, and integrin beta1, has important clinical implications, including its potential ability to regulate tumor sensitivity to selected chemotherapies and to influence tumor migration/metastases and tumorigenesis. Importantly, our recent in vitro and in vivo data support the hypothesis that CD26 may indeed be an appropriate target for therapy for selected cancers and immune disorders. PMID- 17346219 TI - Antivirals of ethnomedicinal origin: structure-activity relationship and scope. AB - Ethnomedicinal plants have been used as source of candidate drugs for almost all diseases, but the number of compounds having antiviral activity is scarce. Irrespective of type of viruses and the cells they infect, there are a very few specific viral targets for the natural molecules to interact. Most of the available antiviral drugs often lead to the development of viral resistance coupled with the problem of side effects, recurrence and viral latency. A wide array of ethnomedicinal plants showed high level of antiviral activities and many of them have complementary and overlapping mechanism of action, either inhibiting viral replication, or viral genome synthesis. Hence, there is an urgent need to develop new antivirals of natural origin. This review will cover some of the promising antiviral compounds isolated from ethnomedicinal plants with proven in vitro and some documented in vivo activities, along with their structure activity relationship. PMID- 17346220 TI - Boronated DNA-binding compounds as potential agents for boron neutron capture therapy. AB - Boron Neutron Capture Therapy (BNCT) is a binary cancer treatment that exploits the short range particles released from a nuclear fission reaction involving the non-radioactive 10B nucleus and low-energy (thermal) neutrons for the destruction of tumour cells. If boronated agents are targeted towards chromosomal DNA, the efficiency of BNCT is greatly enhanced. This article presents a concise review of DNA-binding compounds that have been functionalised with boron. PMID- 17346221 TI - Antioxidants derived from vitamin E: an overview. AB - Alpha-tocopherol is a very well-known potent antioxidant and radical scavenger in chemical and biological systems. Its structure has served as starting point for design and synthesis of more potent antioxidant analogues with regard to its potential clinical and nutritional applications in human health. Furthermore, in recent years, intense research has been made not only in the development of hybrid compounds with classical drug moieties in a single molecule, but also in the preparation of label analogues with application in tocopherol metabolism studies. In the present review principal progresses in these aspects are outlined. PMID- 17346222 TI - Raxofelast, (+/-)5-(acetyloxy)-2,3-dihydro-4,6,7-trimethyl-2-benzofuranacetic acid: a new antioxidant to modulate the inflammatory response during ischemia reperfusion injury and impaired wound healing. AB - Raxofelast, also named IRFI 016 or (+/-)5-(acetyloxy)-2,3-dihydro-4,6,7-trimethyl 2-benzofuranacetic acid, belongs to a family of novel molecules designed with the aim to maximize antioxidant potency of phenols related to Vitamin E (alpha tocopherol). This review will focus on the antioxidant and radical scavenging activity of this new promising compound. PMID- 17346223 TI - Influence of conformationally constrained amino acids replacing positions 2 and 3 of arginine vasopressin (AVP) and its analogues on their pharmacological properties. AB - Synthesis of thirteen new analogues of arginine vasopressin (AVP) has been described. Amino acid residues at positions 2 and 3 of AVP, [3-mercaptopropionic acid (Mpa)(1)]AVP (dAVP), [Mpa(1),d-Arg(8)]VP (dDAVP) and [Mpa(1),Val(4),d Arg(8)]VP (dVDAVP) were replaced with one amino acid residue using sterically constrained non-proteinogenic amino acids, 4-aminobenzoic acid (Abz), cis-4 aminocyclohexanecarboxylic acid (ach) or its trans-isomer (Ach). In the case of a potent V(1a) antagonist, [1-mercaptocyclohexaneacetic acid (Cpa)(1)]AVP, only one similar analogue has been prepared by replacing positions 2 and 3 with Abz. Unfortunately, all new peptides were inactive in bioassays for the pressor, antidiuretic and uterotonic in vitro activities in the rat. PMID- 17346224 TI - Oligomerisation of sarcoplasmic reticulum Ca2+-ATPase monomers from skeletal muscle. AB - The fast-twitch SERCA1 isoform of the sarcoplasmic reticulum Ca(2+)-ATPase was purified to homogeneity and conjugated to peroxidase. The SERCA1 probe showed high affinity binding to the immobilized monomeric enzyme, but not crosslinker stabilized oligomers. This suggests a preferential complex formation via homo dimerization, rather than interactions with established oligomeric structures. PMID- 17346225 TI - The ways of realization of high specificity and efficiency of enteropeptidase. AB - Comparative substrate analysis of full-length bovine enteropeptidase and trypsin, bovine and human enteropeptidase light chains was performed using model N terminal dodecapeptides corresponding to wild-type human trypsinogen and pancreatitis-associated mutant trypsinogens K23R and D22G. The substitution of Lys residue by Arg at P1 leads to 2-fold increase in the efficiency of enteropeptidase hydrolysis; the absence of the negatively charged residue at P2 reduces the efficiency of such hydrolysis by two orders of magnitude. The difference in efficiency of peptide chain hydrolysis after Lys/Arg residues by enteropeptidase compared to trypsin is equal to the difference in hydrolysis by serine proteases of different primary specificity of their specific substrates. PMID- 17346226 TI - Stem bromelain: an enzyme that naturally facilitates oriented immobilization. AB - The lone oligosaccharide chain of stem bromelain was oxidized with periodic acid to generate aldehyde groups and the resulting oxidized enzyme coupled to amino Sepharose in order to obtain an immobilized preparation with uniformly oriented enzyme. The immobilized bromelain exhibited high proteolytic activity and remarkably enhanced thermal stability as compared to soluble bromelain and that coupled to CNBr activated Sepharose. PMID- 17346228 TI - High-level expression and purification of an analgesic peptide from Buthus martensii Karch. AB - BmK AngM1, a scorpion peptide isolated from Buthus martensii Karch was reported to exhibit potential analgesic effect. But the relative low content of this toxin in crude venom limits its further characterization. In this study, we constructed an expression vector and transformed into E.coli. The BmK AngM1 was expressed as a fusion protein in the soluble fraction and was purified by Nickel affinity chromatography. Subsequently, the purified fusion protein was cleaved by enterokinase and was further purified by reverse-phase HPLC. We purified 25 mg recombinant BmK AngM1 (rBmK AngM1) from 1 L bacterial culture. The molecular weight of rBmK AngM1 determined by ESI-MS was 7240.4 Da which was the expected size for correctly processed. Analgesic bioassay studies of rBmK AngM1 exhibited its potential analgesic effect comparable to that of the natural BmK AngM1 peptide. PMID- 17346229 TI - Structural insights into the exchange domain of sec2p: expression, purification, crystallization, and preliminary x-ray diffraction data analysis. AB - Sec2p is an essential yeast gene and is part of the cell polarization process that leads to budding. The N-terminal domain of sec2p (Sec2pN)--the guanine nucleotide exchange factor for sec4p--has been expressed in Escherichia coli, purified, and crystallized. Crystals belong to the space group P2(1) with unit cell dimensions 178.1 x 98.4 x 180.0 A, beta = 91.7( degrees ), and diffract synchrotron-generated X-rays to better than 3.6 A resolution. Pseudo-precession plots reveal a Laue symmetry of 2/m, corresponding to the aforementioned space group, and unusual weak diffraction in the approximately 5-7 A resolution range. The Matthews number calculations for a typical crystal density suggest a range of 28 to 64 molecules per asymmetric unit. Self-rotation and native Patterson calculations demonstrate a pure helical array of protein subunits. Based on the X ray diffraction data analysis and amino-acid sequence alignments, the paper presents a hypothetical model of the exchange domain of sec2p as a pair of coiled coil helices that binds to sec4p and facilitates nucleotide disassociation. PMID- 17346227 TI - Critical enzymes involved in endocannabinoid metabolism. AB - Investigations of the pathways involved in the metabolism of endocannabinoids have grown exponentially in recent years following the discovery of cannabinoid receptors (CB) and their endogenous ligands, such as anandamide (AEA) and 2 arachidonoylglycerol (2-AG). The in vivo biosynthesis of AEA has been shown to occur through several pathways mediated by N-acylphosphatidylethanolamide phospholipase D (NAPE-PLD), a secretory PLA(2) and PLC. 2-AG, a second endocannabinoid is generated through the action of selective enzymes such as phosphatidic acid phsophohydrolase, diacylglycerol lipase (DAGL), phosphoinositide-specific PLC (PI-PLC) and lyso-PLC. A putative membrane transporter or facilitated diffusion is involved in the cellular uptake or release of endocannabinoids. AEA is metabolized by fatty acid amidohydrolase (FAAH) and 2-AG is metabolized by both FAAH and monoacylglycerol lipase (MAGL). The author presents an integrative overview of current research on the enzymes involved in the metabolism of endocannabinoids and discusses possible therapeutic interventions for various diseases, including addiction. PMID- 17346230 TI - Design, synthesis and utilization of 1- substituted sulphonyloxy-2-phenyl benzimidazole as a novel peptide coupling reagents. AB - Highly efficient coupling reagents, N-methanesulphonyloxy-2-phenyl benzimidazole and N - p-toluenesulphonyloxy-2-phenyl benzimidazole were designed, synthesized and successfully applied in peptide coupling reactions. Their efficiency was evaluated by synthesizing a number of structurally different amides and peptides as well. The distereomeric purity was examined by HPLC. Also the optical rotations of all the synthesized peptides were measured and found to be quite matching with corresponding values in literature. After completion of reaction, the N-hydroxy 2-phenyl benzimidazole which was the starting material for the synthesis of reagents could be easily isolated during the work up by acid base treatment and could be re-used without significant loss in reactivity. Also the intermediate in the reaction sequence was isolated and characterized by mass and (1)H NMR which could help to comment about the probable mechanism. PMID- 17346231 TI - Cautionary tail: the presence of an N-terminal tag on dynein light-chain Roadblock/LC7 affects its interaction with a functional partner. AB - As part of structural investigations of components of the molecular motor, dynein, we prepared the light chain, Robl1_mouse, with and without an N-terminal His-tag. We found that the His-tag introduced a spurious binding site for a second protein, IC74. We propose a molecular mechanism for functional interference by the His-tag. PMID- 17346232 TI - Biological evaluation of fluorinated p-boronophenylalanine derivatives as a boron carrier. AB - Boron neutron capture therapy (BNCT) and magnetic resonance imaging (MRI) are quite attractive techniques for treatment and diagnosis of cancer, respectively. In order to develop practical materials utilizing both for BNCT and MRI, fluorinated p-boronophenylalanines and their alcohol derivatives had already been designed and synthesized. In the present paper the cytotoxicity, the incorporated amount into cancer cells, and the tumor cell killing effects of these compounds were elucidated to evaluate their usefulness as a boron carrier. PMID- 17346233 TI - Radiolabeled peptides and proteins in cancer therapy. AB - With the advances in genomics, molecular biology including gene vector technologies today's molecular imaging modalities have strongly been improved. The major progress is based on peptide and antibody targeting vectors. When labeled with beta(-)-emitting radioisotopes these agents are applicable for endoradiotherapy and exploit the targeting potential for highly specific therapeutic applications. This novel class of pharmaceuticals offers the potential to develop patient specific therapies and might provide the means to go beyond the possibilities of current chemotherapy and radiation therapy. In this review the basic principles of endoradiotherapeutics based on peptides and proteins are presented. Several of these drugs such as (90)Y-rituximab (Zevalin), (131)I-tositumomab (Bexxar) and the somatostatin receptor binding (90)Y-DOTATOC that are nowadays successfully applied in oncological therapy are discussed. Future generations of endoradiopharmaceuticals will address yet unknown targets which might be identified by screening techniques such as ribosome and phage display peptide libraries. PMID- 17346234 TI - The helical structure propensity in the first helix of the histidine phosphocarrier protein of Streptomyces coelicolor. AB - The bacterial phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS), formed by a cascade of several proteins, mediates the uptake and phosphorylation of carbohydrates, and it is also involved in signal transduction. Its uniqueness in bacteria makes the PTS a target for new antibacterial drugs. These drugs can be obtained from peptides or proteins fragments able to interfere the first step of the protein cascade: the phosphorylation of the HPr protein by the enzyme EI. We designed a peptide comprising the active site and the first alpha-helix of HPr of S. coelicolor; we also obtained a fragment of HPr by protein engineering methods, comprising the first forty-eight residues and thus, containing the amino acids of the shorter peptide. Both fragments were disordered in aqueous solution, with a similar percentage of helical structure ( approximately 7 %), and an identical free energy of helix formation. In 40 % TFE, both fragments acquired native-like helical structure, stabilized by non-native hydrophobic interactions, as shown by the 2D-NMR assignments of the shorter peptide, and the presence of similar NOE contacts in both fragments. These findings, with the kinetic results in other members of the HPr family, highlight the importance of short- and long range interactions during the folding reaction of HPr proteins. Based on the residual helical population, hypothesis about the inhibition capacity of the PTS by both fragments are discussed. PMID- 17346235 TI - Genome-wide analysis of enzyme structure-function combination across three domains of life. AB - To investigate diverse enzyme structure-function combination (SFC) types in different species, 34 different genome sequences were annotated using the protein catalytic domain database SCOPEC (http://www.enzome.com/enzome/), in which both the structure and function for each entry are known. Annotated enzymes with catalytic domains from the same SCOP superfamily are considered to have an identical structure. Annotated enzymes sharing the identical three-digit EC number are considered to have the same enzymatic function. Results reveal that the different SFC types for enzymes identified in archaea, bacteria and eukaryota are 137, 300 and 313, respectively. About 80% of the SFCs identified in archaea can be consistently found in bacteria and eukaryota species, whereas 28% and 35% combination types in bacteria and eukaryota respectively are unique to their corresponding groups. The number of functions per structure and the number of structures per function for the annotated sequences were measured in different species. Furthermore, a new concept was proposed to represent enzymatic structures as a functional similarity network. Thus, the current study will be helpful to enhance the global view on the evolution of enzymatic structure and function. PMID- 17346236 TI - T-cell antigen receptor assembly and cell surface expression is not affected by treatment with T-cell antigen receptor-alpha chain transmembrane Peptide. AB - A synthetic peptide termed core peptide (CP), which corresponds to a specific sequence of the TCR-alpha chain transmembrane domain, is known to inhibit IL-2 production in antigen stimulated T-cells. The molecular mechanism of the TCR inhibition is not known. This study examined the effects of CP on TCR subunit assembly and TCR cell surface expression in vitro. Co-transfection experiments between TCR-alpha and CD3-delta using COS-7 cells, and the interaction between TCR-alpha and the CD3 proteins in a T-cell line (2B4) were analysed after incubation with CP or its conjugates. Results indicate that CP co-precipitates with CD3-delta and CD3-epsilon in vitro, without any effect on TCR-alpha/CD3 delta dimerisation or TCR multisubunit assembly and cell surface expression. PMID- 17346237 TI - Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins. AB - The sequential processing of the APP (amyloid precursor protein) by the beta- and gamma-secretase and generation of the Abeta (amyloid-beta) peptide is a primary pathological factor in AD (Alzheimer's disease). Regulation of the processing or turnover of these proteins represents potential targets for the development of AD therapies. Sumoylation is a process by which SUMOs (small ubiquitin-like modifiers) are covalently conjugated to target proteins, resulting in a number of functional consequences. These include regulation of protein-protein interactions, intracellular trafficking and protein stability, which all have the potential to impact on several aspects of the amyloidogenic pathway. The present study examines the effects of overexpression and knockdown of the major SUMO isoforms (SUMO1, 2 and 3) on APP processing and the production of Abeta peptides. SUMO3 overexpression significantly increased Abeta40 and Abeta42 secretion, which was accompanied by an increase in full-length APP and its C-terminal fragments. These effects of SUMO3 were independent of its covalent attachment or chain formation, as mutants lacking the motifs responsible for SUMO chain formation or SUMO conjugation led to similar changes in Abeta. SUMO3 overexpression also up regulated the expression of the transmembrane protease BACE (beta-amyloid cleaving enzyme), but failed to affect levels of several other unrelated proteins. Suppression of SUMO1 or combined SUMO2+3 by RNA interference did not affect APP levels or Abeta production. These findings confirm a specific effect of SUMO3 overexpression on APP processing and the production of Abeta peptides but also suggest that endogenous sumoylation is not essential and likely plays an indirect role in modulating the amyloid processing pathway. PMID- 17346238 TI - Selenophosphate synthetase 2 is essential for selenoprotein biosynthesis. AB - Selenophosphate synthetase (SelD) generates the selenium donor for selenocysteine biosynthesis in eubacteria. One homologue of SelD in eukaryotes is SPS1 (selenophosphate synthetase 1) and a second one, SPS2, was identified as a selenoprotein in mammals. Earlier in vitro studies showed SPS2, but not SPS1, synthesized selenophosphate from selenide, whereas SPS1 may utilize a different substrate. The roles of these enzymes in selenoprotein synthesis in vivo remain unknown. To address their function in vivo, we knocked down SPS2 in NIH3T3 cells using small interfering RNA and found that selenoprotein biosynthesis was severely impaired, whereas knockdown of SPS1 had no effect. Transfection of SPS2 into SPS2 knockdown cells restored selenoprotein biosynthesis, but SPS1 did not, indicating that SPS1 cannot complement SPS2 function. These in vivo studies indicate that SPS2 is essential for generating the selenium donor for selenocysteine biosynthesis in mammals, whereas SPS1 probably has a more specialized, non-essential role in selenoprotein metabolism. PMID- 17346240 TI - Nutrient-responsive mTOR signalling grows on Sterile ground. AB - The control of cell growth, that is cell size, is largely controlled by mTOR (the mammalian target of rapamycin), a large serine/threonine protein kinase that regulates ribosome biogenesis and protein translation. mTOR activity is regulated both by the availability of growth factors, such as insulin/IGF-1 (insulin-like growth factor 1), and by nutrients, notably the supply of certain key amino acids. The last few years have seen a remarkable increase in our understanding of the canonical, growth factor-regulated pathway for mTOR activation, which is mediated by the class I PI3Ks (phosphoinositide 3-kinases), PKB (protein kinase B), TSC1/2 (the tuberous sclerosis complex) and the small GTPase, Rheb. However, the nutrient-responsive input into mTOR is important in its own right and is also required for maximal activation of mTOR signalling by growth factors. Despite this, the details of the nutrient-responsive signalling pathway(s) controlling mTOR have remained elusive, although recent studies have suggested a role for the class III PI3K hVps34. In this issue of the Biochemical Journal, Findlay et al. demonstrate that the protein kinase MAP4K3 [mitogen-activated protein kinase kinase kinase kinase-3, a Ste20 family protein kinase also known as GLK (germinal centre-like kinase)] is a new component of the nutrient-responsive pathway. MAP4K3 activity is stimulated by administration of amino acids, but not growth factors, and this is insensitive to rapamycin, most likely placing MAP4K3 upstream of mTOR. Indeed, MAP4K3 is required for phosphorylation of known mTOR targets such as S6K1 (S6 kinase 1), and overexpression of MAP4K3 promotes the rapamycin-sensitive phosphorylation of these same targets. Finally, knockdown of MAP4K3 levels causes a decrease in cell size. The results suggest that MAP4K3 is a new component in the nutrient-responsive pathway for mTOR activation and reveal a completely new function for MAP4K3 in promoting cell growth. Given that mTOR activity is frequently deregulated in cancer, there is much interest in new strategies for inhibition of this pathway. In this context, MAP4K3 looks like an attractive drug target since inhibitors of this enzyme should switch off mTOR, thereby inhibiting cell growth and proliferation, and promoting apoptosis. PMID- 17346239 TI - Identification and biochemical characterization of two novel UDP-2,3-diacetamido 2,3-dideoxy-alpha-D-glucuronic acid 2-epimerases from respiratory pathogens. AB - The heteropolymeric O-antigen of the lipopolysaccharide from Pseudomonas aeruginosa serogroup O5 as well as the band-A trisaccharide from Bordetella pertussis contain the di-N-acetylated mannosaminuronic acid derivative, beta-D ManNAc3NAcA (2,3-diacetamido-2,3-dideoxy-beta-D-mannuronic acid). The biosynthesis of the precursor for this sugar is proposed to require five steps, through which UDP-alpha-D-GlcNAc (UDP-N-acetyl-alpha-D-glucosamine) is converted via four steps into UDP-alpha-D-GlcNAc3NAcA (UDP-2,3-diacetamido-2,3-dideoxy alpha-D-glucuronic acid), and this intermediate compound is then epimerized by WbpI (P. aeruginosa), or by its orthologue, WlbD (B. pertussis), to form UDP alpha-D-ManNAc3NAcA (UDP-2,3-diacetamido-2,3-dideoxy-alpha-D-mannuronic acid). UDP-alpha-D-GlcNAc3NAcA, the proposed substrate for WbpI and WlbD, was obtained through chemical synthesis. His6-WbpI and His6-WlbD were overexpressed and then purified by affinity chromatography using FPLC. Capillary electrophoresis was used to analyse reactions with each enzyme, and revealed that both enzymes used UDP-alpha-D-GlcNAc3NAcA as a substrate, and reacted optimally in sodium phosphate buffer (pH 6.0). Neither enzyme utilized UDP-alpha-D-GlcNAc, UDP-alpha-D-GlcNAcA (UDP-2-acetamido-2,3-dideoxy-alpha-D-glucuronic acid) or UDP-alpha-D-GlcNAc3NAc (UDP-2,3-diacetamido-2,3-dideoxy-alpha-D-glucose) as substrates. His6-WbpI or His6-WlbD reactions with UDP-alpha-D-GlcNAc3NAcA produce a novel peak with an identical retention time, as shown by capillary electrophoresis. To unambiguously characterize the reaction product, enzyme-substrate reactions were allowed to proceed directly in the NMR tube and conversion of substrate into product was monitored over time through the acquisition of a proton spectrum at regular intervals. Data collected from one- and two-dimensional NMR experiments showed that His6-WbpI catalysed the 2-epimerization of UDP-alpha-D-GlcNAc3NAcA, converting it into UDP-alpha-D-ManNAc3NAcA. Collectively, these results provide evidence that WbpI and WlbD are UDP-2,3-diacetamido-2,3-dideoxy-alpha-D glucuronic acid 2-epimerases. PMID- 17346241 TI - Chimaerins: GAPs that bridge diacylglycerol signalling and the small G-protein Rac. AB - Chimaerins are the only known RhoGAPs (Rho GTPase-activating proteins) that bind phorbol ester tumour promoters and the lipid second messenger DAG (diacylglycerol), and show specific GAP activity towards the small GTPase Rac. This review summarizes our knowledge of the structure, biochemical and biological properties of chimaerins. Recent findings have established that chimaerins are regulated by tyrosine kinase and GPCRs (G-protein-coupled receptors) via PLC (phospholipase C) activation and DAG generation to promote Rac inactivation. The finding that chimaerins, along with some other proteins, are receptors for DAG changed the prevalent view that PKC (protein kinase C) isoenzymes are the only cellular molecules regulated by DAG. In addition, vigorous recent studies have begun to decipher the critical roles of chimaerins in the central nervous system, development and tumour progression. PMID- 17346242 TI - PKCzeta protects against UV-C-induced apoptosis by inhibiting acid sphingomyelinase-dependent ceramide production. AB - In a recent study, we described that UV-C irradiation resulted in redox-dependent activation and relocalization of A-SMase (acid sphingomyelinase) to the external surface of raft membrane microdomains, hydrolysis of SM (sphingomyelin) associated with the plasma membrane outer leaflet, ceramide generation and apoptosis. In the present study, we have investigated the influence of PKCzeta (protein kinase Czeta), an atypical form of PKC on this pathway. This study shows that PKCzeta overexpression resulted in the abrogation of UV-C-induced A-SMase translocation and activation into the raft microdomains, lack of ceramide generation and apoptosis inhibition. Moreover, PKCzeta overexpression resulted in a decrease in UV-C-induced ROS (reactive oxygen species) production, which correlated with increased gene expression level of various antioxidant enzymes, including TRx (thioredoxin), TR (thioredoxin reductase) 1, TR2 and peroxiredoxin 1/TPx2 (thioredoxin peroxidase 2). Importantly, enforced TPx2 gene expression inhibited UV-C-induced A-SMase translocation. Finally, PKCzeta inhibition led to a significant reduction in TPx2 protein expression. Altogether, these results suggest that PKCzeta interferes with the UV-activated sphingolipid signalling pathway by regulating the TRx system. These findings may have important consequences for UV-induced carcinogenesis and resistance to phototherapy. PMID- 17346243 TI - Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology. AB - The intracellular signal transduction of AngII (angiotensin II) has been implicated in cardiovascular diseases, such as hypertension, atherosclerosis and restenosis after injury. AT(1) receptor (AngII type-1 receptor), a G-protein coupled receptor, mediates most of the physiological and pathophysiological actions of AngII, and this receptor is predominantly expressed in cardiovascular cells, such as VSMCs (vascular smooth muscle cells). AngII activates various signalling molecules, including G-protein-derived second messengers, protein kinases and small G-proteins (Ras, Rho, Rac etc), through the AT(1) receptor leading to vascular remodelling. Growth factor receptors, such as EGFR (epidermal growth factor receptor), have been demonstrated to be 'trans'-activated by the AT(1) receptor in VSMCs to mediate growth and migration. Rho and its effector Rho kinase/ROCK are also implicated in the pathological cellular actions of AngII in VSMCs. Less is known about the endothelial AngII signalling; however, recent studies suggest the endothelial AngII signalling positively, as well as negatively, regulates the NO (nitric oxide) signalling pathway and, thereby, modulates endothelial dysfunction. Moreover, selective AT(1)-receptor-interacting proteins have recently been identified that potentially regulate AngII signal transduction and their pathogenic functions in the target organs. In this review, we focus our discussion on the recent findings and concepts that suggest the existence of the above-mentioned novel signalling mechanisms whereby AngII mediates the formation of cardiovascular diseases. PMID- 17346245 TI - Synergistic combinations of anticonvulsant agents: what is the evidence from animal experiments? AB - PURPOSE: Combination therapy is often used in the treatment of seizures refractory to monotherapy. At the same time, the pharmacodynamic mechanisms that determine the combined efficacy of antiepileptic drugs (AEDs) are unknown, and this prevents a rational use of these drug combinations. We critically evaluate the existing evidence for pharmacodynamic synergism between AEDs from preclinical studies in animal models of epilepsy to identify useful combinations of mechanisms and to determine whether study outcome depends on the various research methods that are in use. METHODS: Published articles were included if the studies were placebo-controlled, in vivo, or ex vivo animal studies investigating marketed or experimental AEDs. The animal models that were used in these studies, the primary molecular targets of the tested drugs, and the methods of interpretation were recorded. The potential association of these factors with the study outcome (synergism: yes or no) was assessed through logistic regression analysis. RESULTS: In total, 107 studies were identified, in which 536 interaction experiments were conducted. In 54% of these experiments, the possibility of a pharmacokinetic interaction was not investigated. The majority of studies were conducted in the maximal electroshock model, and other established models were the pentylenetetrazole model, amygdala kindling, and the DBA/2 model. By far the most widely used method for interpretation of the results was evaluation of the effect of a threshold dose of one agent on the median effective dose (ED50) of another agent. Experiments relying on this method found synergism significantly more often compared with experiments relying on other methods (p<0.001). Furthermore, experiments including antagonists of the AMPA receptor were more likely to find synergism in comparison with all other experiments (p<0.001). CONCLUSIONS: Intensive preclinical research into the effects of AED combinations has not led to an understanding of the pharmacodynamic properties of AED combinations. Specifically, the majority of the preclinical studies are not adequately designed to distinguish between additive, synergistic, and antagonistic interactions. Quantitative pharmacokinetic pharmacodynamic studies of selectively acting AEDs in a battery of animal models are necessary for the development of truly synergistic drug combinations. PMID- 17346246 TI - Compulsory generic switching of antiepileptic drugs: high switchback rates to branded compounds compared with other drug classes. AB - PURPOSE: Compulsory generic substitution of antiepileptic drugs (AEDs) may lead to adverse effects in epilepsy patients because of seizure recurrence or increased toxicity. The study objectives were (a) to quantify and compare the switchback rates from generic to brand-name AEDs versus non-AEDs, and (b) to assess clinical implications of switching from branded Lamictal to generic lamotrigine (LTG) and whether signals exist suggesting outcome worsening. METHODS: By using a public-payer pharmacy-claims database from Ontario, Canada, switchback rates from generic to branded AEDs [Lamictal, Frisium (clobazam; CLB), and Depakene (VPA; divalproex)] were calculated and compared with non-AED long term therapies, antihyperlipidemics and antidepressants, in January 2002 through March 2006. We then assessed pharmacy utilization and AED dosage among LTG patients switching back to branded Lamictal compared with those staying on generic formulation. RESULTS: The 1,354 patients (403 monotherapy, 951 polytherapy) were prescribed generic LTG, of whom 12.9% switched back to Lamictal (11.7% monotherapy, 13.4% polytherapy). Switchback rates of other AEDs were approximately 20% for CLB and VPA. The switchback rates for AEDs were substantially higher than for non-AEDs (1.5-2.9%). Significant increases in LTG doses were observed after generic substitution for those who did not switch back (6.2%; p<0.0001). The average number of codispensed AEDs and non-AED drugs significantly increased (p<0.0001) after LTG generic entry, especially in the generic group. CONCLUSIONS: These results reflect poor acceptance of switching AEDs to generic compounds. They may also indicate increased toxicity and/or loss of seizure control associated with generic AED use. PMID- 17346247 TI - Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. AB - PURPOSE: This study evaluates the effect of oral contraceptives on lamotrigine (LTG) plasma concentrations and urine excretion of LTG metabolites in a double blind, placebo-controlled, crossover study in patients with epilepsy. METHODS: Women with epilepsy, treated with LTG in monotherapy and taking combination-type oral contraceptives, were randomized to treatment with placebo or a standard combination-type contraceptive pill. The dose-corrected trough plasma concentration of LTG and the ratio of N-2-glucuronide/unchanged LTG on urine after 21 days of concomitant placebo treatment was analyzed versus those after 21 days of concomitant treatment with the oral contraceptive pill. RESULTS: The mean dose-corrected LTG concentration after placebo treatment was 84%[95% confidence interval (CI), 45-134%] higher than after oral contraceptives, signifying an almost doubling of the concentration after cessation of oral contraceptives. Most of this increase took place within the first week after oral contraceptives were stopped. The N-2-glucuronide/LTG ratio in the urine was decreased by 31% (95% CI, -20-61%) when shifting from oral contraceptives to placebo. CONCLUSIONS: Cessation of oral contraceptives leads to an 84% increase in the concentration of LTG. In parallel, the excretion of the N-2-glucuronide was decreased, indicating that the changes are caused by altered LTG glucuronidation. The change in LTG concentrations was observed within 1 week of the shift of treatment, suggesting that induction and deinduction of LTG glucuronidation is faster than that seen for other metabolic pathways (e.g., cytochrome P450). PMID- 17346248 TI - A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine on cyp3a4. AB - PURPOSE: Carbamazepine (CBZ) and oxcarbazepine (OXCZ) are well-known inducers of drug metabolism via CYP3A4. Indirect interaction studies and clinical experience suggest that CBZ has a stronger potential in this regard than OXCZ. However this has never been subject to a direct comparative study. We performed a study in healthy volunteers to investigate the relative inductive effect of CBZ and OXCZ on CYP3A4 activity using the metabolism of quinidine as a biomarker reaction. METHODS: Ten healthy, male volunteers participated in an open, randomized crossover study consisting of two periods separated by a 4-week wash-out period. The subjects received 1200 mg oral OXCZ daily for 17 days and 800 mg oral CBZ for 17 days. A single 200 mg oral dose of quinidine was administered at baseline and following administration of CBZ and OXCZ. Outcome parameters were the formation clearance of 3-hydroxyquinidine dose and the ratio of the AUCs of 3 hydroxyquinidine to quinidine. RESULTS: Formation clearance of 3-hydroxyquinidine was increased by means of 89% (CI: 36-164; p=0.0022) and 181% (CI: 120-260, p<0.0001) after treatment with OXCZ and CBZ, respectively, compared to baseline. The relative inductive effect of CBZ was 46% higher than for OXCZ. AUC ratio increased by means of 161% (CI: 139-187, p<0.0001) (OXCZ) and 222% (CI: 192-257, p<0.0001) (CBZ). Quinidine Cmax decreased by means of 29% (CI: 16-40, p=0.0018) (OXCZ) and 33% (CI: 18-45, p=0.0020) (CBZ). T1/2 decreased by means of 12% (CI: 6 17, p<0.0014) (OXCZ) and 32% (CI: 25-38, p<0.0001) (CBZ). tmax was not changed in either period. CONCLUSION: We confirm a clinically significant inductive effect of both OXCZ and CBZ. The inductive effect of CBZ was about 46% higher than that of OXCZ, a difference that may be of clinical relevance. PMID- 17346249 TI - Clinical seizure lateralization in frontal lobe epilepsy. AB - PURPOSE: We systematically analyzed the lateralizing value of clinical seizure semiology in patients with frontal lobe epilepsy (FLE). METHODS: We studied the incidence, positive predictive value (PPV), and the lateralizing significance of various clinical symptoms in 228 seizures (s) of 31 patients (p) with medically refractory FLE (17 with left-sided and 14 with right-sided seizure onset). Seizures recorded during prolonged video-EEG monitoring were assessed by two independent reviewers blinded for the patient's clinical data. Analysis was performed both for patients and seizures. RESULTS: Version [16 p (52%); PPV, 94%; p=0.001; 47 s (21%); PPV, 75%; p=0.001], unilateral clonic movements [16 p (52%); PPV, 81%; p=0.021; 32 s (14%); PPV, 81%; p=0.001], unilateral dystonic posturing [eight p (26%); PPV, 75%; p=0.289; 46 s (20%); PPV, 80%; p=0.001], unilateral tonic posturing [10 p (32%); PPV, 80%; p=0.109; 19 s (7.4%); PPV, 79%; p=0.019], and unilateral grimacing [10 p (32%); PPV, 100%; p=0.002; 19 s (8%); PPV, 100%; p=0.001] were of lateralizing significance, indicating a contralateral seizure onset. Asymmetric ending [five p (16%); PPV, 80%; p=0.375; nine s (4%); PPV, 89%; p=0.039] after secondarily generalized tonic-clonic seizures was significantly associated with an ipsilateral seizure onset. Pure ictal vocalizations occurred significantly more frequently in seizures of right hemispheric onset [13 p (42%); PPV, 62%; p=0.581; 63 s (28%); PPV, 73%; p=0. 001], whereas in individual patients, this symptom showed no lateralizing significance. The remaining clinical symptoms (figure 4 sign, unilateral hand automatisms, early head turning, postictal nose wiping, and unilateral eye blinking) were not of lateralizing significance in our patients. The results of clinical seizure lateralization corresponded with the final lateralization of the seizure-onset zone in 81% of our patients. CONCLUSIONS: Clinical seizure semiology can provide correct information on the lateralization of the seizure-onset zone in >80% of patients with medically refractory frontal lobe epilepsy. PMID- 17346250 TI - The role of the intracarotid amobarbital procedure in predicting verbal memory decline after temporal lobe resection. AB - PURPOSE: The aim of this study was to compare the utility of baseline neuropsychological measures and scores from the intracarotid amobarbital procedure (IAP) in the prediction of postoperative memory decline in temporal lobe epilepsy surgery patients. METHODS: Logistic regression analyses were used to determine the relation between demographic variables, baseline neuropsychological scores, and scores from the IAP (using mixed verbal and nonverbal stimuli) and postoperative deterioration in verbal learning and verbal recall in 91 patients (48 right, RTL; 43 left, LTL) who had undergone a standard anterior temporal lobe resection for the relief of medically intractable epilepsy and who had been followed up 1 year postoperatively. RESULTS: In the RTL group, the IAP scores were not significant predictors of a postoperative decline in verbal learning or recall. In the LTL group, postoperative decline in verbal learning was associated with good preoperative baseline scores, an older age at the time of surgery, and an unexpected asymmetry on the IAP. Baseline neuropsychological scores and scores from the IAP were associated with a significant postoperative decline in verbal recall in the LTL group. CONCLUSIONS: Scores from the IAP using mixed stimuli were not helpful in the prediction of postoperative verbal memory decline in RTL patients. The significance of IAP scores in predicting verbal memory deficits in LTL patients may be task specific. PMID- 17346251 TI - Seizure outcome after resection of supratentorial cavernous malformations: a study of 168 patients. AB - PURPOSE: The optimal management of cerebral cavernous malformations (CCMs) with epileptic seizures is still a matter of debate. The aim of our study was to examine seizure outcome in the largest published series of surgically treated patients with epilepsy due to a supratentorial CCM, and to define predictors for good surgical outcome. METHODS: We retrospectively studied 168 consecutive patients with a single supratentorial CCM and symptomatic epilepsy in a multicenter study. Pre- and postoperative clinical examinations, age at epilepsy onset, age at operation, type of symptoms due to the CCM (seizures, headache, hemorrhage, focal deficits), type and frequency of epileptic seizures, and the localization and size of the CCM were assessed. Seizure outcome was determined in the first, second, and third postoperative years. RESULTS: The CCM was completely resected in all patients. More than two thirds of the patients were classified as seizure free in the first 3 postoperative years. Predictors for good seizure outcome were age older than 30 years at the time of surgery, mesiotemporal CCM localization, CCM size <1.5 cm, and the absence of secondarily generalized seizures. No mortality occurred in our series, but only mild postoperative neurologic deficits in 12 (7%) patients. CONCLUSIONS: Considering the natural history of CCMs, the favorable neurologic and seizure outcome, surgical resection of CCMs should be considered in all patients with supratentorial CCMs and concomitant epilepsy, irrespective of the presence or absence of predictors for a favorable seizure outcome. PMID- 17346252 TI - Does SISCOM contribute to favorable seizure outcome after epilepsy surgery? AB - PURPOSE: To assess the additional value of subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) for localization of the epileptogenic zone in patients with drug-resistant epilepsy scheduled for invasive video-EEG (VEEG) before epilepsy surgery by a descriptive study from clinical practice. METHODS: Forty-nine consecutive epilepsy patients between January 2000 and March 2006 were included. Thirty-six of the 49 patients were offered surgery, and 34 underwent resective surgery during the study period. Localizing and outcome data are presented from 31 patients with a follow-up period of >or=12 months. Successful ictal SPECT was performed in 26 patients, and SISCOM showed significant hyperperfusions with 3.5 SD above reference. Twenty patients had SISCOM-guided electrode placement, invasive monitoring, and 1-year postsurgical follow-up data. Two independent epileptologists evaluated whether SISCOM results (a) altered the hypothesis and extended the strategy for electrode placement at invasive recording, or (b) were confirmatory of other localizing data and did not alter the strategy. We defined that SISCOM had an impact on seizure outcome if the seizure-onset zone was seen in electrodes overlying a brain region with a significant hyperperfusion. When SISCOM was concordant with ictal onset in the extended electrodes, SISCOM was considered a prerequisite for the outcome at postoperative follow-up. RESULTS: SISCOM findings altered and extended the strategy for electrode placement at invasive recording in 15 patients (group A). SISCOM was a prerequisite for seizure outcome in all six patients with favorable outcomes. Nine patients had poor results from surgery in this group; SISCOM was concordant with invasive VEEG in six patients, and discordant with invasive VEEG in three patients. SISCOM findings were confirmatory with other localizing data and did not alter the strategy at invasive recording in five patients (group B). Two patients had favorable surgical outcomes. In this group, three patients had poor results; SISCOM and other localizing findings were concordant with invasive VEEG in one patient and discordant with invasive VEEG in two patients. CONCLUSIONS: SISCOM is valuable for the identification of the epileptogenic zone in patients with drug-resistant epilepsy scheduled for invasive VEEG. SISCOM analysis was either a prerequisite for favorable result or concordant with other localizing methods in all patients with favorable seizure outcome at 1 year of follow-up [40%; confidence interval (CI), 19-64). PMID- 17346253 TI - Experience with generic drugs in epilepsy patients: an electronic survey of members of the German, Austrian and Swiss branches of the ILAE. PMID- 17346254 TI - Severe relapse of epilepsy after vigabatrin withdrawal: for how long should we treat symptomatic infantile spasms? PMID- 17346255 TI - Short telomeres in short-lived males: what are the molecular and evolutionary causes? AB - Telomere length regulation is an important aspect of cell maintenance in eukaryotes, since shortened telomeres can lead to a number of defects, including impaired cell division. Although telomere length is correlated with lifespan in some bird species, its possible role in aging and lifespan determination is still poorly understood. Here we investigate telomere dynamics (changes in telomere length and attrition rate) and telomerase activity in the ant Lasius niger, a species in which different groups of individuals have evolved extraordinarily different lifespans. We found that somatic tissues of the short-lived males had dramatically shorter telomeres than those of the much longer-lived queens and workers. These differences were established early during larval development, most likely through faster telomere shortening in males compared with females. Workers did not, however, have shorter telomeres than the longer-lived queens. We discuss various molecular mechanisms that are likely to cause the observed sex-specific telomere dynamics in ants, including cell division, oxidative stress and telomerase activity. In addition, we discuss the evolutionary causes of such patterns in ants and in other species. PMID- 17346256 TI - Accounting for genotyping errors in tagging SNP selection. AB - One limitation of the existing tagging SNP selection algorithms is that they assume the reported genotypes are error free. However, genotyping errors are often unavoidable in practice. Many tagging SNP selection methods depend heavily on the estimated haplotype frequencies. Recent studies have demonstrated that even slight genotyping errors can lead to serious consequences with regard to haplotype reconstruction and frequency estimation. Here we present a tagging SNP selection method that allows for genotyping errors. Our method is a modification of the pair-wise r(2) tagging SNP selection algorithm proposed by Carlson et al. (2004). We have replaced the standard EM algorithm in Carlson's method with an EM that accounts for genotyping errors, in an attempt to obtain better estimates of the haplotype frequencies and r(2) measure. Through simulation studies we compared the performance of our modified algorithm with that of the original algorithm. We found that the number of tags selected by both methods increased with increasing genotyping errors, though our method led to smaller increase. The power of haplotype association tests using the selected tags decreased dramatically with increasing genotyping errors. The power of single marker tests also decreased, but the reduction was not as much as the reduction in power of haplotype tests. When restricting the mean number of tags selected by both methods to be similar to the baseline number, Carlson's method and our method led to similar power for the subsequent haplotype and single marker tests. Our results showed that, by accounting for random genotyping errors, our method can select tagging SNPs more efficiently than Carlson's method. The computer program that implements our modified tagging SNP selection algorithm is available at our web site: http://www.personal.psu.edu/tuy104/. PMID- 17346257 TI - Ethnic differences in interleukin 6 (IL-6) and IL6 receptor genes in spontaneous preterm birth and effects on amniotic fluid protein levels. AB - Preterm birth (PTB) is a significant neonatal health problem that is more common in African-Americans (AA) than in European-Americans (EA). Part of this disparity is likely to result from the differing genetic architectures of EA and AA. To begin assessing the role of these differences, patterns of genetic variation in two previously proposed candidate genes, encoding interleukin 6 (IL6) and its receptor (IL6R), were analyzed in mothers and fetuses from 496 EA birth-events (149 cases and 347 controls) and 397 birth-events in AA (76 cases and 321 controls). IL-6 levels in amniotic fluid (AF) samples were determined in a subset of these pregnancies. Case-control comparisons revealed a single SNP in IL6R associated with PTB (p=0.04 for allelic and p=0.05 for genotype association). In addition, all of the SNPs studied showed significant frequency differences between AA and EA in at least one comparison, significantly in excess of that expected from general population databases. Higher IL-6 concentrations were associated with the IL6 SNP -661 in EA preterm samples (p=0.0056), and this result seems to be driven by microbial invasion of the amniotic cavity, indicating a gene by infection interaction. These findings indicate that, as a function of IL6 genotype, EA and AA women respond differently to infection with respect to their expression of IL-6. Our data support differential genetic control of levels of IL-6 in amniotic fluid between EA and AA. PMID- 17346258 TI - Confidence intervals for candidate gene effects and environmental factors in population-based association studies of families. AB - Complex diseases are influenced by both genetic and environmental factors. Studies of individuals or of families can be used to examine the association of genetic factors, such as candidate genes, and other risk factors with the presence or absence of complex disorders. If families are investigated, whether or not they are randomly ascertained, possible familial correlation among observations must be considered. We have compared two statistical approaches for analyzing correlated binary data from randomly ascertained nuclear families. The generalized estimating equations approach (GEE) can be used to adjust for familial correlation. The relationship between covariates and the response is modelled, and the correlations among family members are treated as nuisance parameters. For comparison, we have proposed two strategies from a hierarchical nonparametric bootstrap approach. One strategy (S1) samples family units, preserving the structure and correlation within each family. A second and novel strategy (S2) also samples family units but then randomly samples offspring with replacement in each family. We applied the methods to data from a study of cardiovascular disease, and followed up with a simulation study in which family data were generated from an underlying multifactorial genetic model. Although the bootstrap approach was more computationally demanding, it outperformed the GEE in terms of confidence interval coverage probabilities for all sample sizes considered. PMID- 17346260 TI - Dynamics of yeast populations recovered from decaying leaves in a nonpolluted stream: a 2-year study on the effects of leaf litter type and decomposition time. AB - Here we report on the results of a survey of the yeast populations occurring on submerged leaves (alder, eucalyptus and oak) in a natural mountain stream, during different phases of their decomposition and through two consecutive years. Leaf litter mass loss, total yeast counts, Shannon-Weiner index (H'), yeast community structure and physiologic abilities were analyzed to evaluate the dynamics of yeast communities during decay. Seventy-two yeast taxa were recorded, and in all litter types, species of basidiomycetous affinity predominated over ascomycetous ones. Discriminant analysis of presence/absence data (yeast species) showed significant differences both among substrate types (P<0.0026) and with decomposition time (P<0.0001). Carbon and nitrogen source utilization by yeast strains also varied with the substrate (P<0.0001) and decomposition time (P<0.0001). Further conclusions were that: (1) all litter types have in common ubiquitous yeast species, such as Cryptococcus albidus, Debaryomyces hansenii and Rhodotorula glutinis, among the common 20 yeast species; (2) only a few species were dominant, and most species were rare, being recorded once or twice throughout decomposition; and (3) the order of yeast appearance, and their substrate assimilation patterns, strongly suggest a succession phenomenon. Finally, explanations for the distribution patterns and variations in yeast communities are discussed. PMID- 17346261 TI - Phytochrome A is an irradiance-dependent red light sensor. AB - Plants perceive red (R) and far-red (FR) light signals using the phytochrome family of photoreceptors. In Arabidopsis thaliana, five phytochromes (phyA-phyE) have been identified and characterized. Unlike other family members, phyA is subject to rapid light-induced proteolytic degradation and so accumulates to relatively high levels in dark-grown seedlings. The insensitivity of phyA mutant seedlings to prolonged FR and wild-type appearance in R has led to suggestions that phyA functions predominantly as an FR sensor during the early stages of seedling establishment. The majority of published photomorphogenesis experiments have, however, used <50 micromol m(-2) sec(-1) of R when characterizing phytochrome functions. Here we reveal considerable phyA activity in R at higher (>160 micromol m(-2) sec(-1)) photon irradiances. Under these conditions, plant architecture was observed to be largely regulated by the redundant actions of phytochromes A, B and D. Moreover, quadruple phyBphyCphyDphyE mutants containing only functional phyA displayed R-mediated de-etiolation and survived to flowering. The enhanced activity of phyA in continuous R (Rc) of high photon irradiance correlates with retarded degradation of the endogenous protein in wild type plants and prolonged epifluorescence of nuclear-localized phyA:YFP in transgenic lines. Such observations suggest irradiance-dependent 'photoprotection' of nuclear phyA in R, providing a possible explanation for the increased activity observed. The discovery that phyA can function as an effective irradiance sensor, even in light environments that establish a high Pfr concentration, raises the possibility that phyA may contribute significantly to the regulation of growth and development in daylight-grown plants. PMID- 17346262 TI - crinkled leaves 8--a mutation in the large subunit of ribonucleotide reductase- leads to defects in leaf development and chloroplast division in Arabidopsis thaliana. AB - The crinkled leaves8 (cls8) mutant of Arabidopsis thaliana displays a developmental phenotype of abnormal leaf and flower morphology, reduced root growth and bleached leaf sections. Map-based cloning identified the mutation as being within the gene encoding the large subunit of ribonucleotide reductase (RNR1), the enzyme that catalyses the rate-limiting step in the production of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis and repair. Levels of dTTP and dATP were significantly reduced in cls8. Two further mutant cls8 alleles and cls8::RNAi plants show similar or more severe phenotypes. The cls8-1 mutant has fewer copies of the chloroplast genome, and fewer, larger chloroplasts than wild-type plants. The ultrastructure of the chloroplast, however, appears normal in cls8-1 leaves. We present evidence that, under conditions of limited dNTP supply, the inhibition of chloroplast DNA replication may be the primary factor in inducing aberrant growth. PMID- 17346263 TI - Regulation and functional analysis of ZmDREB2A in response to drought and heat stresses in Zea mays L. AB - DREB1/CBFs and DREB2s are transcription factors that specifically interact with a cis-acting element, DRE/CRT, which is involved in the expression of genes responsive to cold and drought stress in Arabidopsis thaliana. The function of DREB1/CBFs has been precisely analyzed and it has been found to activate the expression of many genes responsive to cold stress containing a DRE/CRT sequence in their promoters. However, the regulation and function of DREB2-type transcription factors remained to be elucidated. In this research, we report the cloning of a DREB2 homolog from maize, ZmDREB2A, whose transcripts were accumulated by cold, dehydration, salt and heat stresses in maize seedlings. Unlike Arabidopsis DREB2A, ZmDREB2A produced two forms of transcripts, and quantitative real-time PCR analyses demonstrated that only the functional transcription form of ZmDREB2A was significantly induced by stresses. Moreover, the ZmDREB2A protein exhibited considerably high transactivation activity compared with DREB2A in Arabidopsis protoplasts, suggesting that protein modification is not necessary for ZmDREB2A to be active. Constitutive or stress inducible expression of ZmDREB2A resulted in an improved drought stress tolerance in plants. Microarray analyses of transgenic plants overexpressing ZmDREB2A revealed that in addition to genes encoding late embryogenesis abundant (LEA) proteins, some genes related to heat shock and detoxification were also upregulated. Furthermore, overexpression of ZmDREB2A also enhanced thermotolerance in transgenic plants, implying that ZmDREB2A may play a dual functional role in mediating the expression of genes responsive to both water stress and heat stress. PMID- 17346264 TI - Detection and identification of rhamnogalacturonan lyase activity in intercellular spaces of expanding cotton cotyledons. AB - Rhamnogalacturonan lyase (RG lyase) activity has been detected and its relative activity measured in vivo during the expansion of cotton (Gossypium hirsutum L.) cotyledons. Rhamnogalacturonan (RG) oligomers labeled with a fluorescent tag were injected into the intercellular spaces of cotton cotyledons and, after incubation, the digested substrate was rinsed out. Enzyme digestion products were detected and identified by capillary zone electrophoresis. Rhamnogalacturonan lyase products were identified as such by co-migration with the digestion products of linear RG oligomers when the oligomers were treated with fungal RG lyase but not when treated with fungal RG hydrolase. In addition, reaction of plant RG lyase digestion products of RG oligomers with I(2)/KI, which selectively removes unsaturated galactopyranosyluronic acid (GaLap) residues formed at the non-reducing end of the oligomer, converted the plant digestion products into RG oligomers that co-migrated with fungal RG hydrolase products. The activity of the enzyme in the intercellular spaces of cotton cotyledons is very low and could be detected most easily when not >0.03 nmol of substrate was injected in a approximately 0.7-cm(2) area and incubated in vivo for 2-6 h. Rhamnogalacturonan lyase activity was the highest in rapidly expanding 3- to 4-day-old cotyledons and gradually decreased during the slow-down in expansion over the next 2-3 days. The RG lyase activity was also detected when the APTS (8-aminopyrene-1,3,6 trisulfonic acid, trisodium salt)-labeled substrates were introduced into intercellular spaces by infiltration instead of injection, indicating that the activity was not induced by wounding or released into the apoplast by cell damage. An exo-RG galacturonohydrolase activity was also found, but RG hydrolase and exo-RG rhamnohydrolase were not detected. PMID- 17346265 TI - MAX2 participates in an SCF complex which acts locally at the node to suppress shoot branching. AB - The Arabidopsis gene ORE9/MAX2 encodes an F-box leucine-rich repeat protein. F box proteins function as the substrate-recruiting subunit of SCF-type ubiquitin E3 ligases in protein ubiquitination. One of several phenotypes of max2 mutants, the highly branched shoot, is identical to mutants at three other MAX loci. Reciprocal grafting, double mutant analysis and gene cloning suggest that all MAX genes act in a common pathway, where branching suppression depends on MAX2 activity in the shoot, in response to an acropetally mobile signal that requires MAX3, MAX4 and MAX1 for its production. Here, we further investigate the site and mode of action of MAX2 in branching. Transcript analysis and a translational MAX2 GUS fusion indicate that MAX2 is expressed throughout the plant, most highly in developing vasculature, and is nuclear-localized in many cell types. Analysis of cell autonomy shows that MAX2 acts locally, either in the axillary bud, or in adjacent stem or petiole tissue. Expression of MAX2 from the CaMV 35S promoter complements the max2 mutant, does not affect branching in a wild-type background and partially rescues increased branching in the max1, max3 and max4 backgrounds. Expression of mutant MAX2, lacking the F-box domain, under the CaMV 35S promoter does not complement max2, and dominant-negatively affects branching in the wild type background. Myc-epitope-tagged MAX2 interacts with the core SCF subunits ASK1 and AtCUL1 in planta. We conclude that axillary shoot growth is controlled locally, at the node, by an SCF(MAX2), the action of which is enhanced by the mobile MAX signal. PMID- 17346266 TI - RNA-directed RNA polymerase 1 (RdR1) mediates the resistance of Nicotiana attenuata to herbivore attack in nature. AB - Small RNAs are important regulators of plant development and resistance to viruses. To determine whether small RNAs mediate defense responses to herbivore attack, we silenced the expression of three RNA-directed RNA polymerases (RdRs) in the native tobacco Nicotiana attenuata by virus-induced gene silencing. Larvae of the leaf-chewing solanaceous specialist Manduca sexta grew faster on the RdR1 silenced plants than on empty vector (EV) controls; silencing RdR3 and 2 had little to no effect on larval performance. NaRdR1 transcripts were strongly elicited when puncture wounds were treated with M. sexta oral secretions (OS) to simulate herbivore attack, and with SA and JA, phytohormones that are elicited by herbivore attack. Stably silencing RdR1 by transforming N. attenuata with an inverted-repeat RdR1 construct produced plants (irRdR1) that grew normally but were highly susceptible to both M. sexta larvae and the cell-content-feeder Tupiocoris notatus. When irRdR1 lines were planted into N. attenuata's native habitat in the Great Basin Desert (Utah, USA), they were highly susceptible to herbivore attack, due to deficiencies in direct rather than indirect defenses. Microarray analysis revealed the downregulation of ADC and ODC genes, which supply substrates for synthesizing the chemical defense compound nicotine; irRdR1 lines failed to accumulate nicotine after attack. We conclude that RdR1 mediates herbivore resistance, and infer that the small RNAs produced by RdR1 are probably involved in orchestrating some of the rapid metabolic adjustments required for plants to survive herbivore attack in their natural habitats. The experiment highlights the value of carrying out 'real-world' tests of gene function early in the discovery process. PMID- 17346267 TI - A functional genetic assay for nuclear trafficking in plants. AB - The receptor importin-alpha mediates the nuclear import of functionally diverse cargo proteins that contain arginine/lysine-rich nuclear localization signals (NLSs). Functional homologs of importin-alpha have been characterized in a wide range of species including yeast, human and plants. However, the differential cargo selectivity of plant importin-alpha homologs has not been established. To advance nuclear import studies conducted in plant cells, we have developed a method that allows importin-alpha-dependent nuclear import to be assayed in Nicotiana benthamiana. We employed virus-induced gene silencing (VIGS) to knock down the expression of two importin-alpha homologs, NbImpalpha1 and NbImpalpha2, which we identified from N. benthamiana. Agro-infiltration was then used to transiently express the NLS-containing proteins Arabidopsis thaliana fibrillarin 1 (AtFib1) and the Nuk6, Nuk7 and Nuk12 candidate effector proteins of the oomycete plant pathogen Phytophthora infestans. In this manner, we demonstrate importin-alpha-dependent nuclear import of Nuk6 and Nuk7. In contrast, the nuclear import of Nuk12 and AtFib1 was unaffected in cells of NbImpalpha-silenced plants. These data suggest that P. infestans Nuk6 and Nuk7 proteins are dependent on one or more alpha-importins for nuclear import. Our VIGS-based assay represents a powerful new technique to study mechanisms underlying the transport of proteins from cytoplasm to nucleus in plants. PMID- 17346268 TI - An NB-LRR protein required for HR signalling mediated by both extra- and intracellular resistance proteins. AB - Tomato (Solanum lycopersicum) Cf resistance genes confer hypersensitive response (HR)-associated resistance to strains of the pathogenic fungus Cladosporium fulvum that express the matching avirulence (Avr) gene. Previously, we identified an Avr4-responsive tomato (ART) gene that is required for Cf-4/Avr4-induced HR in Nicotiana benthamiana as demonstrated by virus-induced gene silencing (VIGS). The gene encodes a CC-NB-LRR type resistance (R) protein analogue that we have designated NRC1 (NB-LRR protein required for HR-associated cell death 1). Here we describe that knock-down of NRC1 in tomato not only affects the Cf-4/Avr4-induced HR but also compromises Cf-4-mediated resistance to C. fulvum. In addition, VIGS using NRC1 in N. benthamiana revealed that this protein is also required for the HR induced by the R proteins Cf-9, LeEix, Pto, Rx and Mi. Transient expression of NRC1(D481V), which encodes a constitutively active NRC1 mutant protein, triggers an elicitor-independent HR. Subsequently, we transiently expressed this auto activating protein in N. benthamiana silenced for genes known to be involved in HR signalling, thereby allowing NRC1 to be positioned in an HR signalling pathway. We found that NRC1 requires RAR1 and SGT1 to be functional, whereas it does not require NDR1 and EDS1. As the Cf-4 protein requires EDS1 for its function, we hypothesize that NRC1 functions downstream of EDS1. We also found that NRC1 acts upstream of a MAP kinase pathway. We conclude that Cf-mediated resistance signalling requires a downstream NB-LRR protein that also functions in cell death signalling pathways triggered by other R proteins. PMID- 17346269 TI - Systematic review of early vs deferred hormonal treatment of locally advanced prostate cancer: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: To compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC), as radiotherapy is currently the standard treatment for LAPC, with hormonal treatment considered a reserve option. METHODS: We systematically reviewed randomized controlled trials (RCTs) in patients with LAPC treated with standard care (radical prostatectomy, radiotherapy, and/or watchful waiting) or standard care plus hormonal treatment. Outcomes assessed were mortality and objective disease progression. The meta-analysis used a fixed-effects model. RESULTS: Of the 108 trials identified, seven met the inclusion criteria and were of sufficient quality to be included in the analysis. Early intervention with hormonal treatment significantly reduced all-cause mortality compared with deferred treatment (relative risk, RR, 0.86; 95% confidence interval, CI, 0.82 0.91; P < 0.001). Similarly, early vs deferred use of hormonal treatment significantly reduced: prostate cancer- specific mortality (RR 0.72; 95% CI 0.65 0.79); overall progression (RR 0.74; 0.69-0.78); local progression (RR 0.65; 0.57 0.73); and distant progression (RR 0.67; 0.61-0.74; all P < 0.001). Results were robust to changes in inclusion/exclusion criteria and use of a random-effects model for the meta-analyses. Heterogeneity and publication bias had no significant effect on the analyses. CONCLUSIONS: Early intervention with hormonal treatment for patients with LAPC provides significantly lower mortality and objective disease progression than deferring their use until standard care has failed. PMID- 17346270 TI - Nitric oxide produced in the testis is involved in dilatation of the internal spermatic vein that compromises spermatogenesis in infertile men with varicocele. AB - OBJECTIVE: To determine the concentration of nitric oxide (NO) and the location and change in the expression of NO synthase (NOS) isoforms in the testes of subfertile men with varicocele, and to compare the NO concentration or NOS expression with clinical variables, to determine the role of NO on the pathophysiology of varicocele. PATIENTS AND METHODS: In all, 27 men who had a left varicocelectomy and five with 'normal' spermatogenesis (controls) who had scrotal surgery for other reasons were enrolled. Intratesticular fluid was taken from the men and the NO concentration determined colorimetrically. The expression and location of NOS isoforms were examined by Western blotting and immunohistochemistry, using testicular biopsy specimens, and NADPH-diaphorase (NADPH-d) staining used to identify NO-producing cells. The relationship between the NO concentration and the expression of NOS isoforms or clinicopathological variables was investigated. RESULTS: In testes with grade 2 and 3 varicoceles there were significant increases in the concentration of NO or the expression of inducible NOS. There was no change in the expressions of endothelial NOS, which is located in vascular endothelial cells, while NADPH-d activity was mainly located in these cells. The concentration of NO was significantly correlated with the maximum and total vein diameter (both P<0.01). In patients aged>35 years, the concentration of NO significantly correlated with a deterioration in total motile sperm count (P<0.05). CONCLUSIONS: Increased production of NO in the testis is involved in the enlargement of varicocele and indirectly deteriorates spermatogenesis. PMID- 17346271 TI - Normal anatomy of the external urethral meatus in boys: implications for hypospadias repair. AB - Both papers in this section relate to the always difficult subject of hypospadias repair. One of them describes the anatomy of the external urethral meatus, and the other a technique for repairing coronal or subcoronal hypospadias. OBJECTIVE: To investigate the normal external urethral meatal anatomy in boys, and to examine the proportional relationship between meatal length and degree of ventral glans closure. PATIENTS AND METHODS: In all, 92 boys with presumed normal penile anatomy were considered eligible for the study; 17 were not assessed because either the boy or parents declined to participate, leaving 75 boys (mean age 6.9 years, range 0.3-15) who completed the study. Photographic records of the meatal appearance were obtained and meatal height and ventral glans closure measured using ophthalmic callipers. RESULTS: All 75 boys in the study had a vertical slit like meatus that commenced at the tip of the penis and ran ventrally. The mean (sd) vertical meatal length was 5.4 (1) mm and the mean length of ventral glans closure was 4.7 (1.2) mm. There was an age-dependent increase in meatal length and a similar association was identified for the length of ventral glans closure. There was also a statistically significant proportional relationship between meatal length and length of glans closure (r = 0.36, confidence interval 0.14 0.54, P < 0.002). CONCLUSION: The position and size of the external urethral meatus in normal boys is consistent, and ventral glans closure is equal to or slightly less than meatal length. These data might be of interest to hypospadiologists in their efforts to reconstruct normal glanular anatomy. PMID- 17346272 TI - Survival of patients with transitional cell carcinoma of the ureter and renal pelvis in Balkan endemic nephropathy and non-endemic areas of Serbia. AB - OBJECTIVE: To evaluate the characteristics and survival of patients with upper urinary tract (UUT) transitional cell carcinoma (TCC) in Serbia, followed for >/=5 years or until death. PATIENTS AND METHODS: From 1998 to 2005 we analysed 114 cases of pathologically confirmed UUT TCC, divided into two groups according to topographical characteristics, and compared their demographic, clinical and pathological characteristics. The influence of various factors on overall 5-year survival of patients with UUT TCC was also tested. The prognostic value of different variables was assessed by univariate and multivariate Cox proportional hazard models. RESULTS: The most important change in demographic characteristics of the patients with UUT TCC in Serbia was a similar proportion of patients residing in areas of Balkan endemic nephropathy (BEN) and non-endemic areas. The median (range) follow-up was 67 (46-88) months. The 5-year probability of survival was 51.2 +/- 5.8%. There was a significantly lower probability of 5-year survival for patients with a higher histological grade (P = 0.001), higher T stage (P < 0.001) and tumour size >3 cm (P = 0.001) at diagnosis. In this cohort of patients the independent predictors of a poorer outcome of the disease were being female (hazard ratio, HR, 2.2, P = 0.010), tumour size >3 cm (HR 2.8, P = 0.001) and T3 or T4 stages (HR 3.1, P = 0.001). CONCLUSION: Comparative analysis of the characteristics of UUT TCC between patients from BEN and non-endemic areas of Serbia showed similarities in demographic, clinical and pathological features. Factors that significantly influenced survival of patients with UUT TCC were being female, tumour size and tumour grade and stage. PMID- 17346273 TI - The meatal mobilization technique for coronal/subcoronal hypospadias repair. AB - OBJECTIVE: To describe meatal mobilization (MEMO) by distal urethral preparation as an improved surgical technique for distal hypospadias repair, including glanular, coronal and subcoronal location of the meatus, with or without chordee. PATIENTS AND METHODS: From May 2002 to June 2006, 46 patients (mean age 3.8 years, range 1.5-14) had a repair of glanular, coronal and subcoronal hypospadias using the MEMO technique. A description of the procedure and the results are presented. RESULTS: The mean duration of surgery was 73 min; there were no complications during surgery in any of the patients. The follow-up was 28.5 months; after surgery one patient developed a haematoma, which resolved with no further treatment. There was neither recurrence nor any new episode of chordee or meatal stenosis. None of the patients developed a urethral fistula. In one patient the meatus retracted but remained in the glans. CONCLUSIONS: Complications were minimal and the cosmetic results excellent using the MEMO technique for correcting most of distal hypospadias. PMID- 17346274 TI - Histopathological alterations of the vas deferens in rats exposed to polypropylene mesh. AB - OBJECTIVE: To assess the histological and physiological effects of polypropylene mesh for inguinal herniorraphy, as it can cause lesions in the vas deferens in 0.3-2.0%, leading to infertility, and induces an inflammatory process and adjacent fibrosis, strengthening the posterior inguinal wall. MATERIALS AND METHODS: In all, 40 male albino rats (3 months old) had bilateral vas deferens dissection followed by mesh implantation on one side; the contralateral side was used as the control. The rats were killed 90 (group 1) and 120 (group 2) days later, and the vas deferens, epididymides and testicles assessed histopathologically. RESULTS: There was a foreign-body reaction after mesh implantation, but not in the controls. The mean lumen dilatation in regions proximal to the mesh in groups 1 and 2 was 0.468 and 0.371 mm(2), respectively, and all the sections had spermatozoids. The mean dilatation in control groups 1 and 2 was 0.239 and 0.170 mm(2), respectively, with spermatozoids present in 58% and 75%, respectively (significant, P < 0.05). In group 1 the wall thickness of mesh-implanted segments reduced to 0.177 mm, and in segments proximal to the mesh to 0.099 mm; the control segment was 0.298 mm (P < 0.05). In group 2 the mean thickness of mesh-implanted and proximal segments was 0.134 and 0.224 mm, respectively, while in the control it was 0.284 mm (not significant). There was loss of mucosal folding in all segments proximal to the mesh but not in the control. The epididymides and testicles were unchanged. CONCLUSION: Polypropylene mesh induces a foreign-body reaction, with histological changes in the vas deferens that cause functional obstruction, with dilatation and spermatozoid repression. PMID- 17346275 TI - Erlotinib (OSI-774)-induced inhibition of transitional cell carcinoma of bladder cell line growth is enhanced by interferon-alpha. AB - OBJECTIVE: To examine whether erlotinib gives similar results to gefitinib, a small molecule epidermal growth factor receptor (HER1/EGFR) tyrosine kinase (TK) inhibitor that inhibits the growth of human bladder cancer cell lines in vitro, and given that interferon-alpha (IFNalpha) promotes an antiproliferative effect of HER1/EGFR inhibitors on colon cancer cell lines, to also determine the effects of erlotinib alone or together with INFalpha on bladder cancer cell lines, and whether sensitivity is influenced by HER1/EGFR mutation status. MATERIALS AND METHODS: Seven bladder cancer cell lines were characterized for HER1/EGFR expression, then treated with erlotinib alone, IFNalpha alone, or IFNalpha plus erlotinib. Cell growth inhibition was assessed by crystal-violet staining and HER1/EGFR expression by flow cytometry. Synergy was evaluated using the combination index of Chou and Talalay. DNA from these cell lines in the linear growth phase and from 14 bladder cancer tissue samples were tested for HER1/EGFRTK mutations. RESULTS: Cell-surface HER1/EGFR expression was present in all seven bladder cancer cell lines. Both erlotinib and IFNalpha independently were significantly antiproliferative, and combined treatment synergistically enhanced the sensitivity in six of the seven cell lines. No bladder cancer cell lines or tissues tested expressed HER1/EGFRTK mutations. CONCLUSION: Erlotinib inhibits the growth of human bladder cancer cell lines. Enhanced inhibition in the presence of IFNalpha is not determined by the presence of HER1/EGFRTK mutations. This study might have clinical implications for improving the treatment of bladder cancer. PMID- 17346276 TI - Acute acrolein-induced cystitis in mice. AB - OBJECTIVE: To develop a method of direct intravesical administration of acrolein and evaluate the severity of cystitis in response to increasing doses of acrolein in female C57BL/6N (C57) mice, with further studies to compare the severity of acute acrolein-induced cystitis among C57, C3H/HeJ (HeJ), and C3H/OuJ (OuJ) strains of mice, as chemical cystitis produced by the systemic administration of cyclophosphamide is thought to result from renal excretion of hepatic metabolites, particularly acrolein. MATERIALS AND METHODS: Doses of acrolein (0 1000 microg, 15 microL total volume) were instilled into the bladders of C57 female mice; the bladders were removed 4 or 24 h later, weighed, and processed for histology. Acrolein (6 or 10 microg; 15 microL) was instilled into the bladders of C57, HeJ and OuJ female mice, the bladders removed 4 or 24 h later, weighed, and processed for standard histology and immunohistochemical detection of uroplakin. RESULTS: Increasing doses of acrolein up to 100-200 microg caused a linear increase in bladder weight and greater histological evidence of inflammation. Doses of >200 microg caused submaximal increases in bladder weight, apparently due to structural damage of the bladder. Bladder weight and submucosal oedema were consistently greater in C57 and HeJ than OuJ mice. Treatment with acrolein caused loss of urothelium along with uroplakin in some areas of all bladder sections 4 h after treatment. Bladders from C57 mice had some loss of urothelium 24 h after instillation of 6 or 10 microg acrolein, but urothelium and uroplakin covered nearly all the surface of bladders of HeJ and OuJ mice 24 h after treatment. There were significantly more white blood cells in bladders from C57 or HeJ mice than in bladders from OuJ mice 24 h after an instillation of 6 or 10 microg acrolein. CONCLUSIONS: Intravesical instillation of acrolein produces dose-dependent cystitis in mice. OuJ mice appear relatively more resistant to irritant effects of intravesical acrolein than C57 or HeJ mice, and future studies will be directed at identifying genetic causes for these differences. PMID- 17346277 TI - International study into the use of intermittent hormone therapy in the treatment of carcinoma of the prostate: a meta-analysis of 1446 patients. AB - OBJECTIVE: To review pooled phase II data to identify features of different regimens of intermittent hormone therapy (IHT), developed to reduce the morbidity of treating metastatic prostate cancer, and which carries a theoretical advantage of delaying the onset of androgen-independent prostate cancer, (AIPC) that are associated with success, highlighting features which require exploration with prospective trials to establish the best strategies for using this treatment. METHODS: Individual data were collated on 1446 patients with adequate information, from 10 phase II studies with >50 cases, identified through Pubmed. RESULTS: Univariate and multivariate Cox proportional hazard models were developed to predict treatment success with a high degree of statistical success. The prostate-specific antigen (PSA) nadir, the PSA threshold to restart treatment, and medication type and duration, were important predictors of outcome. CONCLUSIONS: The duration of biochemical remission after a period of HT is a durable early indicator of how rapidly AIPC and death will occur, and will make a useful endpoint in future trials to investigate the best ways to use IHT based on the important treatment cycling variables described above. Patients spent a mean of 39% of the time off treatment. The initial PSA level and PSA nadir allow the identification of patients with prostate cancer in whom it might be possible to avoid radical therapy. PMID- 17346278 TI - Colon pouch (Mainz III) for continent urinary diversion. AB - OBJECTIVE: To evaluate the use of a continent cutaneous pouch made exclusively of colon (Mainz pouch III), as excellent results with the Mainz pouch III in irradiated patients suggested that the indication for this type of urinary diversion could be extended. PATIENTS AND METHODS: The outcome of 24 patients with continent cutaneous urinary diversions using colon segments (Mainz pouch III) was investigated retrospectively. Overall, 22 of the patients had a malignant disease and two a benign disease; 16 had a hysterectomy and pelvic exenteration for gynaecological tumours; two men with a rhabdomyosarcoma of the prostate had a radical cystoprostatectomy; one woman had pelvic exenteration for bladder cancer; one man had a simultaneous rectum resection due to infiltrating rectal cancer, and another a left nephrectomy with cystectomy for concomitant kidney and bladder tumour. Benign indications were hyper-reflexive bladder after polytrauma and two cases of neurogenic bladder dysfunction. Eighteen patients had radiotherapy (32-48 Gy) before the urinary diversion. RESULTS: The mean (range) follow-up was 35 (12-65) months. The mean pouch capacity was 293.8 mL. Three patients died during the follow-up (two from disease progression and one suicide); 20 patients were fully continent, four with reduced pouch capacity (<300 mL) had slight incontinence and are wearing a protective pad (band-aid at the umbilicus). All patients use intermittent self-catheterization (mean catheterization frequency 6.8/day, range 6-12). Complications related to the pouch were one outlet stenosis that required revision. Postoperative pouchograms showed asymptomatic reflux in four patients. None of the patients developed metabolic acidosis or diarrhoea. CONCLUSIONS: The Mainz pouch III is an alternative to other types of continent urinary diversion. PMID- 17346279 TI - Painful ejaculation. AB - We reviewed previous publications on post-orgasmic pain with reference to prevalence, epidemiology and treatment options, using the Ovid and PubMed (updated May 2006) databases to comprehensively search MEDLINE for reports on post-orgasmic pain that included peer-reviewed English-language articles. Official proceedings of internationally known scientific societies were also assessed. Because of the heterogeneity of the studies we did not apply meta- analytic techniques to the data. The incidence of post-orgasmic pain is 1-9.7%. The ejaculatory pain is associated with prostatitis, chronic pelvic pain syndrome, benign prostatic hyperplasia, and ejaculatory duct obstruction; it is also described in patients after procedures like radical prostatectomy. Aetiopathogenic theories include those referring to bladder neck closure and pudendal neuropathy. The treatment options vary from self-care, a 'perineal hyperprotection programme' to medication with the alpha-blocker, topiramate, and even surgical procedures like removing a section of the sacrotuberous ligament, neurolysis of the pudendal nerve or removing a section of the sacrospinous ligament. This is the first update of the subject, with reference to prevalence, epidemiology and treatment options. There is a need for adequately powered, prospective randomized trials on aetiology and treatment options. PMID- 17346280 TI - Histamine H4 receptor agonists have more activities than H4 agonism in antigen specific human T-cell responses. AB - Histamine not only mediates immediate allergic reactions, it also regulates cellular immune responses. H4R is the most recently identified histamine receptor (HR). In the present study, we examined the in vitro effect of histamine and H4R agonists on the responses of human T cells to purified protein derivative from Mycobacterium tuberculosis (PPD) and to Cry j1, the major allergen of Cryptomeria japonica pollen. Dimaprit, clobenpropit and clozapine, which are H4R agonists, dose-dependently blocked both PPD-induced interferon-gamma and Cry j1-induced interleukin-5 production by both peripheral blood mononuclear cells (PBMCs) and antigen-specific T-cell lines. However, the addition of thioperamide, an H3R/H4R antagonist, as well as a mixture of d-chlropheniramine, famotidine and thioperamide, did not reverse the inhibition. Pretreatment of PBMCs with SQ22536 and 8-bromoadenosine-3',5'-cyclic monophosphorothioate, Rp-isomer, had varying abilities to reverse the inhibitory effects of H4R agonists, except for clobenpropit. Moreover, the addition of H4R agonists induced annexin-V expression on PBMCs, especially in CD19(+) and CD4(+) cells. cDNA microarray analysis revealed that, among 16,600 genes tested, increased expression following treatment with clozapine was seen in 0 x 8% of the genes, whereas decreased expression was seen in 3 x 0% of the genes. These results suggest that H4R agonists inhibit antigen-specific human T-cell responses, although H4R does not appear to be important for this effect. In addition, the present study indicated that there may be orphan receptors or HR subtypes which can bind dimaprit, clobenpropit and clozapine, and that can exert an inhibitory effect on antigen specific cellular responses via a cAMP/cAMP-dependent protein kinase-dependent, apoptotic pathway. PMID- 17346281 TI - In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection. AB - Human natural killer (NK) cells form a circulating population in a state of dynamic homeostasis. We investigated NK cell homeostasis by labelling dividing cells in vivo using deuterium-enriched glucose in young and elderly healthy subjects and patients with viral infection. Following a 24-hr intravenous infusion of 6,6-D(2)-glucose, CD3(-) CD16(+) NK cells sorted from peripheral blood mononuclear cells (PBMC) by fluorescence-activated cell sorter (FACS) were analysed for DNA deuterium content by gas chromatography mass spectrometry to yield minimum estimates for proliferation rate (p). In healthy young adults (n=5), deuterium enrichment was maximal approximately 10 days after labelling, consistent with postmitotic maturation preceding circulation. The mean (+/- standard deviation) proliferation rate was 4 x 3 +/- 2 x 4%/day (equivalent to a doubling time of 16 days) and the total production rate was 15 +/- (7 x 6) x 10(6) cells/l/day. Labelled cells disappeared from the circulation at a similar rate [6 x 9 +/- 4 x 0%/day; half-life (T((1/2))) < 10 days]. Healthy elderly subjects (n=8) had lower proliferation and production rates (P=2 x 5 +/- 1 x 0%/day and 7 x 3 +/- (3 x 7) x 10(6) cells/l/day, respectively; P=0 x 04). Similar rates were seen in patients chronically infected with human T-cell lymphotropic virus type I (HTLV-I) (P=3 x 2 +/- 1 x 9%/day). In acute infectious mononucleosis (n=5), NK cell numbers were increased but kinetics were unaffected (P=2 x 8 +/- 1 x 0%/day) a mean of 12 days after symptom onset. Human NK cells have a turnover time in blood of about 2 weeks. Proliferation rates appear to fall with ageing, remain unperturbed by chronic HTLV-I infection and normalize rapidly following acute Epstein-Barr virus infection. PMID- 17346282 TI - Clinical amelioration of murine lupus by a peptide based on the complementarity determining region-1 of an autoantibody and by cyclophosphamide: similarities and differences in the mechanisms of action. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies and systemic clinical manifestations. In this study we investigated the beneficial effects on murine lupus accomplished by a peptide based on the sequence of the complementarity-determining region 1 of an anti-DNA autoantibody (hCDR1) when given alone or in combination with cyclophosphamide (CYC), and determined the mechanisms underlying those effects. SLE-afflicted (NZB x NZW) F(1) mice were treated for 12 weeks with injections of hCDR1, CYC or a combination of both drugs. We found that hCDR1 and CYC ameliorated serological and renal manifestations of the diseased mice, down-regulated interferon-gamma and interleukin-10, and up-regulated transforming growth factor-beta. These effects were associated with an increment of naive CD4(+) cells at the expense of the number of CD4(+) cells with the memory/activated phenotype. Further, the number of CD8(+) cells in the diseased mice was increased by the two drugs, resulting in a significant decrease in the CD4 : CD8 ratio. However, whereas the frequency and activity of CD4(+) CD25(+) CD45RB(low) regulatory T cells and the expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in CD4(+) cells were up regulated by hCDR1 treatment, they were minimally affected following treatment with CYC. CTLA-4 played an important role in the activity of the hCDR1-induced CD4(+) CD25(+) cells as manifested by down-regulation of CD28 expression, decrease of activation-induced apoptosis, and modulation of the cytokine profile in CD4(+) CD25(-) cells derived from SLE-afflicted mice. Thus, although the two drugs have similar ameliorative effects, hCDR1 but not CYC elicits regulatory pathways that are of importance for tolerance induction in SLE. PMID- 17346283 TI - Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro. AB - In different inflammatory disease models, heat-shock proteins (hsp) and hsp derived peptides have been demonstrated to possess anti-inflammatory properties. While some studies have shown that hsp can directly interact with antigen presenting cells, others report that bacterial hsp can induce specific T cells with regulatory phenotypes. Effective characterization of the immunomodulatory effects of hsp 70, however, has historically been confounded by lipopolysaccharide (LPS) contamination. In this study, we compared the effects of LPS-free Mycobacterial tuberculosis hsp 70 (TBhsp70) and its possible contaminants on dendritic cells (DC). We demonstrate herein that LPS-free TBhsp70 inhibits murine DC maturation in vitro, while LPS-contaminated TBhsp70 induces DC maturation. Mock recombinant preparations have no effect. In contrast to LPS, TBhsp70 does not induce tumour necrosis factor-alpha production by DC, but interleukin-10. In vivo, only LPS-contaminated TBhsp70 induces up-regulation of CD86 in splenic mature DC. Finally, TBhsp70 inhibited phytohaemagglutinin-induced T-cell proliferation. Our results support the hypothesis that TBhsp70 does not have inflammatory potential, but rather has immunosuppressive properties. PMID- 17346284 TI - Interleukin-12- and interferon-gamma-mediated natural killer cell activation by Agaricus blazei Murill. AB - Dried fruiting bodies of Agaricus blazei Murill (A. blazei) and its extracts have generally used as complementary and alternative medicines (CAMs). Here, we report that the oral administration of A. blazei augmented cytotoxicity of natural killer (NK) cells in wild-type (WT) C57BL/6, C3H/HeJ, and BALB/c mice. Augmented cytotoxicity was demonstrated by purified NK cells from treated wild-type (WT) and RAG-2-deficient mice, but not from interferon-gamma (IFN-gamma) deficient mice. NK cell activation and IFN-gamma production was also observed in vitro when dendritic cell (DC)-rich splenocytes of WT mice were coincubation with an extract of A. blazei. Both parameters were largely inhibited by neutralizing anti interleukin-12 (IL-12) monoclonal antibody (mAb) and completely inhibited when anti-IL-12 mAb and anti-IL-18 mAb were used in combination. An aqueous extract of the hemicellulase-digested compound of A. blazei particle; (ABPC) induced IFN gamma production more effectively, and this was completely inhibited by anti-IL 12 mAb alone. NK cell cytotoxicty was augmented with the same extracts, again in an IL-12 and IFN-gamma-dependent manner. These results clearly demonstrated that A. blazei and ABPC augmented NK cell activation through IL-12-mediated IFN-gamma production. PMID- 17346285 TI - Interleukin-6 and its mRNA responses in exercise and recovery: relationship to muscle glycogen. AB - Increases in circulating interleukin-6 (IL-6) during exhaustive exercise have been suggested to be related to declining muscle glycogen. We addressed two hypotheses: (a) exhaustive exercise on two occasions will result in similar decreases in glycogen and increases in circulating IL-6 and its muscle mRNA; (b) increasing the rate of glycogen restoration via high-carbohydrate feeding in recovery will be associated with more rapid declines in muscle mRNA and circulating IL-6. Ten male subjects (22.6+/-0.8 year) cycled to exhaustion (65% VO(2 max)) on two occasions (117.8+/-2.9 min). Carbohydrate (1 g/kg bw) or water was ingested at exhaustion, 60, 120, 180, and 240 min post-exercise. Muscle biopsies were taken at rest, exhaustion, 30, 60, 120 and 300 min of recovery. Exercise resulted in a 14.5-fold increase (P<0.05) in IL-6 mRNA, 14.4-fold increase (P<0.05) in circulating IL-6, and a 80% decrease (P<0.05) in muscle glycogen from rest. The decline in glycogen was not correlated with the increase in IL-6 or IL-6 mRNA. During recovery, circulating IL-6 and its muscle mRNA decreased similarly in both trials; however, glycogen increased 150% (P<0.05) and 40% in the carbohydrate and water trials, respectively. Therefore, the declining IL-6 mRNA and IL-6 plasma concentrations during recovery were not related to carbohydrate availability or changes in glycogen. PMID- 17346286 TI - Overreaching-induced oxidative stress, enhanced HSP72 expression, antioxidant and oxidative enzymes downregulation. AB - Overreaching (OVR) is defined as the initial phase of overtraining syndrome and is known as a metabolic imbalance leading to short-term fatigue. Exercise increases reactive oxygen species production, which can oxidize intracellular structures impairing cell function and thus leads to OVR process. The aim of this work is to study the behavior of oxidative stress markers in subjects submitted to an OVR protocol. Thirty rats were divided in exercise and control group, and submitted to an 8-week-endurance training (ET) and a 3-week-OVR protocol. Thiobarbituric acid reactive substances (TBARs), reactive carbonylated derivatives (RCD), glutathione reductase (GR), catalase (CAT) and citrate synthase (CS) activities and stress protein HSP72 were measured in soleus (SO), extensor digital longus (EDL) and semitendinuous (ST) muscles. ET induced significant enhancement (P<0.05) in CS, GR, CAT, TBARs, RCD and HSP72 in SO, EDL and ST. OVR induced higher levels (P<0.05) of TBARs, RCD and HSP72 compared with ET only in SO, while in EDL and ST all measured parameters ranged at same levels reached during ET. We concluded that stress-induced OVR protocol is fiber type dependent, the SO muscle fiber type I being the most affected by this treatment. PMID- 17346287 TI - Failed jump landing trials: deficits in neuromuscular control. AB - The purpose of this investigation was to compare neuromuscular control variables during successful and failed jump landings in multiple directions (sagittal, diagonal, and lateral). All data were collected during a single leg hop stabilization maneuver, which required subjects to stand 70 cm from the center of a force plate, jump off both legs, touch a designated marker placed at a height equivalent to 50% of their maximum vertical jump, and land on a single leg for all directions. Twenty-six subjects [10 males (22+/-3.9 years of age, 70.9+/-7.6 kg, and 176.8+/-0.5 cm) and 16 females (20.6+/-0.5 years of age, 65.6+/-9.1 kg, and 166.4+/-5.9 cm)] volunteered to participate in this investigation. Muscle activation times, average preparatory, and reactive electromyographic (EMG) amplitudes were calculated for the vastus medialis, semi-membranosis, lateral gastrocnemius, and tibialis anterior. EMG data revealed that successful jump landing trials had earlier activation times and higher preparatory and reactive EMG amplitudes. There was no difference for EMG activation times or amplitudes among directions. The results indicate neuromuscular control differences between successful and failed trials because of earlier muscle onset and greater amplitude. The results also suggest that in a healthy population, the direction of the jump protocol will not affect lower extremity EMG characteristics. PMID- 17346288 TI - Effect of exercise-induced muscle damage on endurance running performance in humans. AB - Exercise-induced muscle damage (EIMD) is known to decrease muscle strength and power but its effect on endurance performance is unclear. Thirty moderately trained adult runners (24 men and six women) were randomly assigned to EIMD or control. The EIMD group jumped 100 times from a 35 cm bench, while controls did not perform any muscle-damaging exercise. Before and 48 h after treatment, subjects were tested on markers of EIMD, steady-state cardiorespiratory, metabolic and perceptual responses during a constant speed submaximal run; distance ran in 30 min on a treadmill. There were significant changes in muscle soreness, creatine kinase, and knee extensors strength (P<0.01). This EIMD significantly reduced self-paced time trial performance by 4% (P<0.01) because subjects reduced running speed (P=0.02), with no change in perceived exertion (P=0.31). No significant alterations in running economy and other physiological responses to submaximal running were found. However, there was a trend (P=0.08) for increased perceived exertion, which was correlated with decreased time trial performance (P<0.01). In conclusion, EIMD has a significant impact on endurance running performance in humans, and this effect seems to be mediated by alterations in the sense of effort. PMID- 17346289 TI - Body mass index-independent effect of fitness and physical activity for all-cause mortality. AB - Both obesity and physical inactivity are associated with chronic disease and premature mortality. A review of the literature has shown that both objectively measured level of physical fitness and self-reported physical activity have a prognostic value for all-cause mortality, independently of body mass index. Furthermore, there is evidence for a dose-response effect of physical activity. In conclusion, regular exercise has health-promoting effects, which are beyond its effect on weight control. PMID- 17346290 TI - Rate of reduction of heart rate variability during exercise as an index of physical work capacity. AB - Breathing rates during physical exercise suggest that, during these conditions, the high-frequency (HF) bandwidth of heart rate variability (HRV) analysis should be extended beyond conventional guidelines. However, there has been little investigation of the most appropriate choice of HF bandwidth during exercise. HRV analysis was performed in 10 males and six females during progressive bicycle exercise. Cardiac cycle (RR) interval and breath-by-breath respiratory data were simultaneously recorded. HRV powers were determined for the band-limited ranges 0.04-0.15 Hz [low-frequency (LF)], 0.15-0.4 Hz (HF 0.4) and 0.15-bf Hz (HF bf, where bf represents maximum breathing frequency). Mono-exponential functions described the relationship between HRV and work rate for each bandwidth (r=0.92 0.95) and were used to calculate the "HRV decay constant" (work rate associated with a 50% reduction in HRV power). The HRV decay constants for each bandwidth were linearly related to maximal work rate (r>0.71; P<0.001) and were substantially greater in males than in females (P<0.001). There was a significant difference between the HRV decay constants for HF 0.4 and HF bf (P<0.005) in both genders. The HRV decay constants for the LF and HF bf bandwidths appear to provide an indication of work capacity from submaximal exercise, without prior assumption regarding heart rate and its relationship with work rate. PMID- 17346291 TI - Cross-cultural validity and measurement invariance of the social physique anxiety scale in five European nations. AB - The cross-cultural generalizability of the social physique anxiety scale (SPAS) was evaluated using confirmatory factor analysis (CFA) in five European nations: Britain, Estonia, Spain, Sweden, and Turkey. Motl and Conroy's (2000) methods were used to develop modified versions of the scale within each sample based on the original 12-item version. Pending the satisfactory fit of the CFAs of the modified models within each sample, it was expected that the measurement parameters and mean values of these models would be equivalent across samples in multisample CFAs. An eight-item version of the SPAS exhibited a good fit with data from the British, Estonian, and Swedish samples, and a seven-item version fitted the data well in the Spanish and Turkish samples. The eliminated items were also influenced by a method effect associated with the item wording. Multisample analyses revealed that factor loadings were equivalent across samples. Tests of latent means revealed that British and Spanish participants reported the highest levels of SPA, with Estonian participants reporting the lowest. Results indicate that the SPAS is generalizable across these cultures, although subtle variations existed in the Spanish and Turkish samples. Researchers are advised to follow these procedures to develop a valid version of the SPAS appropriate for their sample. PMID- 17346292 TI - Is active participation in specific sport activities linked with back pain? AB - A cross-sectional survey of 439 children/adolescents aged 12-13, living in Odense, Denmark, in the year 2001. To investigate (1) if there is any difference in back pain reporting among those practising specific sports as compared with non-performers and (2) if there is an association between specific kinds of sports and self-reported back problems. Back pain is a common complaint in young people and physical inactivity is generally thought to contribute to this. However, some specific sport activities may be detrimental or beneficial to the spine. Information was collected through a semi-structured interview, a physical examination, and a questionnaire. Associations for back pain, low back pain, mid back pain and neck pain in the preceding month were investigated in relation to specific sports. Associations were controlled for body mass index, puberty stage and sex. There was no association between back problems and the practising of sports in general. However, some sports were either positively or negatively associated with back pain. Taking into account the relatively small subgroups and multiple testing, some sports seem to be potentially harmful or beneficial. These sports should be investigated in proper longitudinal study designs, in relation to their effects on back problems in the young. PMID- 17346293 TI - Before-birth climatologic data may play a role in the development of allergies in infants. AB - While an exacerbation in allergic symptoms corresponding to seasons has long been reported, few studies have investigated the association between the season of birth and allergic disorders. The aim of this study was to investigate whether the climatologic data before and after birth affected the incidence of atopic dermatitis (AD) and the results of allergy-related blood tests in early infancy. From February 1995 to January 2000, 2136 infants were tested for AD and followed for 12 months. AD patients were tested by using allergy-related blood tests. Data were compared according to the month of birth and the climatologic data using a computed statistical software package. Six hundred and thirty infants had AD before 12 months old, and significant differences were found according to the season of birth (p < 0.0001). Infants born in spring showed the lowest (22.3%) incidence, while those born in autumn showed the highest (34.6%). In 369 patients, total serum IgE levels, and serum specific IgE levels with egg white at 3 months old were also different according to the season of birth. All of these levels were lower in patients born in spring and summer, and higher in patients born in autumn and winter. Furthermore, the cumulative sunshine amount during the 3 months before and after birth was inversely correlated, while the average temperature over the 3 months before birth was positively correlated to the incidence of AD according to the month of birth. The climatologic data around birth may play an important role in whether an infant develops allergies. PMID- 17346294 TI - IL13 gene polymorphism association with cord serum immunoglobulin E. AB - Interleukin-13 (IL-13) has a pivotal role in the pathway of immunoglobulin E (IgE). Cord serum IgE has been suggested to be associated with allergy later in life, yet less affected by environmental exposures. We investigated the association of the interleukin-13 gene (IL13) polymorphisms on cord serum IgE. In the Isle of Wight birth cohort (UK, 1989-1990), cord serum IgE was measured using the ULTRA EIA kit and was dichotomized at 0.5 kU/l (n = 1358). Five single nucleotide polymorphisms (SNPs: rs1800925 in promoter, rs2066960 in intron 1, rs1295686 in intron 3, rs20541 in exon 4 and rs1295685 in exon 4) in IL13 were genotyped by pyrosequencing method. Linkage analysis using Haploview software revealed that rs1295686, rs20541 and rs1295685 were in strong linkage disequilibrium. Logistic regression and Armitage-Cochran test were used and gene association analysis included 798 children. Confounders were maternal age; maternal smoking, household dog, and household cat during pregnancy; season of birth; sex; position of child in family; and birth weight. SNP rs1295685 was associated with raised cord serum IgE (p = 0.031). This is the first report that shows an association between IL13 polymorphism and cord serum IgE. PMID- 17346295 TI - High prevalence of atopy, but not of asthma, among children in an industrialized area in North Italy: the role of familial and environmental factors--a population based study. AB - The prevalence of atopy and asthma, and their association with familial and environmental factors were investigated among 13- to 14-yr-old children living in Brescia, an industrialized town in North Italy. All the 1450 children attending primary school in the town were invited to participate, and 967 of them (66.7%, 493 males) provided a valid questionnaire filled in by their parents at home. We used a modified version of the questionnaire adopted in the Italian Study of Respiratory Disorders in Childhood and Environment, which is an extended version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Six hundred and twenty-eight subjects underwent skin prick test (SPT), and 308 of them (49%) were positive for at least one of the 12 allergen extracts commonly employed. Ninety-nine children (10.2%) had a physician's diagnosis of asthma - 12.4% of the males and 8.0% of the females (p = 0.03). The prevalence of wheezing in the past 12 months was 6.2%. Atopy was found in 76.8% of the subjects with, and in 45.6% of those without physician's diagnosis of asthma (p < 0.001). Analysis by multiple logistic regression showed an inverse association between physician-diagnosed asthma and female sex (odds ratio, OR = 0.5); presence of relatives in the bedroom in initial years of life (OR = 0.6); attending day care (OR = 0.4) and infant school (OR = 0.4); a positive association with parental history of wheezing (OR = 2.5) and asthma (OR = 3.8); and the child's history of asthmatic bronchitis (OR = 31.9) and atopic eczema (OR = 3.8) in the first 2 yr of life. The strength of the associations did not change when restricting the analysis to atopic asthma. In conclusion, atopy and clinical asthma among 13- to 14-yr-old adolescents are significantly associated with some familial and environmental factors, providing further support for the hygiene hypothesis. Prevalence of atopy, but not of asthma, is high in this industrialized area. The strong association found between atopy and clinical asthma suggests that atopy may play a role in causing asthma in genetically predisposed children only. PMID- 17346296 TI - Is neonatal phototherapy associated with an increased risk for hospitalized childhood bronchial asthma? AB - This population-based register study examined if factors during the fetal and neonatal period influence the risk for the child to develop bronchial asthma (asthma). From the Swedish Hospital Discharge Register we identified children, born between 1987 and 1999, who had been hospitalized for asthma up to 2001. Thus, the outcome measure contains only hospitalized cases, not all children with asthma. Children younger than 2 yr at admission were excluded because of the uncertainty about the diagnosis of asthma in younger children. The remaining 14,803 children were compared with all children born the same years, recorded in the Swedish Medical Birth Registry, for information on pre- and perinatal characteristics. Odds ratios (ORs) were calculated with Mantel-Haenszel technique and 95% confidence intervals (CIs) with Miettinen's test-based method. The presence of various maternal and neonatal confounders were identified and adjusted for in the analyses. The association between some known factors and childhood asthma were confirmed: young maternal age, maternal smoking, period of unwanted childlessness, low maternal level of education, maternal diabetes, preterm birth, low birth weight, small-for-gestational age, caesarean section, and instrumental vaginal delivery. A number of neonatal characteristics were shown to be independent risk factors: sepsis or pneumonia, neonatal respiratory problems and treatments, neonatal icterus, and/or neonatal phototherapy. The association with icterus and phototherapy remained after exclusion of cases showing other neonatal risk factors and after adjustment for maternal factors (OR 1.27, 95% CI: 1.08-1.50), and increased to 1.5 if the children had been hospitalized for asthma more than once. In conclusion, our results suggest an association between neonatal icterus and/or treatment with neonatal phototherapy and hospitalized childhood asthma. This association needs further exploration. PMID- 17346297 TI - Action of a silk fabric treated with AEGIS in children with atopic dermatitis: a 3-month trial. AB - Irritation of the skin of patients with atopic dermatitis by contact with rough fibres of synthetic or woollen clothes is well known. Therefore, it has been recommended that patients should wear cotton clothes. However, cotton also consists of rough fibres able to irritate the skin, whereas silk is characterized by smooth fibres without irritating potential. The aim of our study was to evaluate the clinical effect of Dermasilk- a special silk fabric (sericin-free silk treated with AEGIS AEM5772/5 which has antibacterial properties) - in children with atopic dermatitis. A total of 22 children with mild-to-moderate atopic dermatitis were recruited for a study period of 3 months. All of them received three different tube-fabrics - Dermasilk, sericin-free silk fabric without AEGIS AEM 5772/5 and cotton, covering the cubital region. Patients were advised to wear the Dermasilk fabric all day long during the whole study period on one arm, whereas the sericin-free AEGIS-free silk tube had to be used during the first 2 wk only on the other arm followed by the use of the cotton tube for the rest of the study period. Evaluation of the local SCORAD score was carried out at the beginning of the study, after 2, 4, 8 and 12 wk. A significant reduction of the local SCORAD index of the Dermasilk covered arm was observed after 4, 8 and 12 wk in comparison with the cotton-covered arm score [median (quartile 1-quartile 3)] 6.5 (5-8) vs. 8 (7-9), p < 0.002; 6 (5.25-7.75) vs. 8 (7 9), p < 0.0001; and 6 (5-6) vs. 8 (7.25-10), p < 0.0001. The use of Dermasilk has a significant beneficial effect in atopic dermatitis because of the non irritating properties of silk as well as the antibacterial capacity of AEGIS AEM 5772/5. PMID- 17346298 TI - Serum levels of vascular endothelial growth factor in children and adolescents with systemic lupus erythematosus. AB - The angiogenic cytokine vascular endothelial growth factor (VEGF) may have a role in the pathogenesis of collagen diseases. We aimed to assess its serum levels in children and adolescents with systemic lupus erythematosus (SLE) and to elucidate its correlation with clinical features, laboratory parameters, and the overall disease activity. This study comprised 25 children and adolescents with SLE and 30 healthy controls. Disease activity was evaluated by SLE disease activity index (SLEDAI) score. Laboratory investigations included complete blood count, erythrocyte sedimentation rate (ESR), urine analysis, 24-h total urinary protein, assay of serum creatinine, ANA, anti-DNA, complement component C3, lupus anticoagulant, and VEGF. Serum levels of VEGF were significantly increased in SLE patients (579.5 +/- 184.7 pg/ml) when compared with controls (113.2 +/- 30.8 pg/ml) (p < 0.0001). VEGF serum levels were significantly increased in patients having renal involvement and neurologic symptoms than those who did not have them (p < 0.0001, p < 0.005, respectively). Serum levels of VEGF were higher in patients with antiphospholipid syndrome, vasculitis, and skin symptoms than those without, but the difference did not reach statistical significance. Meanwhile, they were similar in patients with and without arthritis (p > 0.05). VEGF serum levels were not correlated to age; inversely correlated to platelet count, serum C3 level; and positively correlated to ESR. SLEDAI score was positively correlated to VEGF serum level (r = 0.86, p < 0.0001). VEGF may be relevant to SLE pathogenesis. Its concentration seems to be a marker of SLE activity, which could help in disease monitoring and planning of treatment. PMID- 17346299 TI - Infant feeding and childhood atopy: does early introduction of non-milk fluids matter? AB - Studies on the role of non-milk fluids in the development of child atopic disease are scarce. We had a unique opportunity to investigate prospective association between the introduction of fruit syrup, orange juice, sterilized water, vitamins and honey at 1 month and the development of child atopic disease. The exposure of interest was measured by parental report of non-milk fluids introduction to infants aged 1 month at the Tasmanian Infant Health Survey, 1988-89, Tasmania. Data on the outcomes of interest (atopic sensitization, asthma, eczema and hay fever) were collected during the 1997 Childhood Allergy and Respiratory Health Study when children were 8 yr old. Relative risks were derived from generalized linear model with a log link function and binomial error structure. None of the non-milk fluids appeared to be a significant predictor of atopic sensitization. Only sterilized water was a significant risk factor for asthma (adjusted relative risk = 1.59; 95% confidence intervals: 1.14-2.22), which may be partly because of associated overall better hygienic conditions and decreased exposure to early infections in the household. In summary, we were unable to find evidence for an association between introduction of non-milk fluids in infancy and childhood atopic disease. PMID- 17346300 TI - Phadiatop compared to skin-prick test as a tool for diagnosing atopy in epidemiological studies in schoolchildren. AB - The validity of the Phadiatop test as compared to the skin-prick test (SPT) for diagnosing atopy in the epidemiological field has not been studied in schoolchildren. The aim of the present study was to evaluate its validity for classifying schoolchildren 9-12 yr old into atopics and non-atopics. A total of 621 children whose parents authorized both a SPT and a blood extraction from all children participating in the phase II of the International Study of Allergies in Children (ISAAC) in Cartagena (Spain) were included in the analysis. A positive SPT was that with at least a wheal having a maximum diameter of 3 mm, once the negative value had been subtracted. Phadiatop was performed according to the manufacturer instructions. Diagnostic tests using SPT as the gold standard were calculated for the whole group of children and also for those with asthma or rhinoconjunctivitis and for children without any of them. The results of the tests were: sensitivity 85.0% (95% CI 82.2-87.8%), specificity 85.5% (95%CI 82.7 88.3%), positive predictive value 72.7% (95%CI 69.0-76.1%), negative predictive value 92.7% (95%CI 90.6-94.7%) and accuracy 85.3% (95%CI 82.3-88.0%). The results improved among the symptomatic groups. Phadiatop can be used as a valid alternative to SPT in the epidemiological setting to diagnose atopy. PMID- 17346301 TI - Asthma attributable to atopy: does it depend on the allergen supply? AB - The use of the population attributable fraction (PAF) of asthma owing to atopy has not been widely used in epidemiological studies on childhood asthma, especially to compare regions of the same country. The present study includes 1039 children from Cartagena, Spain (Mediterranean coast) and 663 from Madrid (centre of Spanish plateau) using the ISAAC phase II methodology (questionnaire and prick test to the most common allergens). While there were no differences in asthma symptoms between school children (aged 10-11 yr) from Madrid and Cartagena, atopy to any allergen was significantly higher in those from Madrid (40.9% vs. 29.3%, respectively, p < 0.0001). However, children from Madrid were mainly positive to pollen allergy whereas those from Cartagena were positive for mite allergy. PAF of all the different asthma symptoms owing to atopy (any positive skin test) and PAF of current wheezing owing to a more severe atopy (three positive wheals) were higher in children from Cartagena than those from Madrid (45.5% vs. 28.6% and 14.2% vs. 6.2%, respectively). Per cent of previous year wheezing attributable to atopy to specific allergens varied among those cities and was higher for D. pteronissinus, D. farinae, cat, and olive tree in children from Cartagena, and--conversely--higher for mixed grasses, mixed trees and Alternaria in those from Madrid. All of these differences remained significant even after adjusting for risk factors. PAF for asthma owing to atopy could be very different within the same country, probably depending on the allergen supply which may depend on environmental factors such as the climate. PMID- 17346302 TI - Sesame food allergy and sensitization in children: the natural history and long term follow-up. AB - Sesame food allergy (SFA) in children is an increasingly recognized one in many countries. Our objective was to describe the course and natural history of SFA. Seventy-four patients sensitized to sesame were evaluated using clinical records, questionnaires, skin prick tests (SPT), in vitro specific immunoglobulin (sIg) E, and oral challenges (OC) and categorized into three groups: group A: patients who experienced allergic reaction after ingestion of sesame-containing food (n = 45); group B: patients evaluated for atopic dermatitis and found to be sesame SPT positive (n = 11); group C: patients with sensitization to sesame allergen (n = 18). Group A patients were followed for an average of 6.7 yr. Analysis of our results revealed that 76% of patients in group A developed the allergy by the age of 2. The median age at onset of allergy in these patients was 1 yr. Immediate reaction to a minimal amount of sesame was characteristic. Skin was the most common site of involvement, followed by respiratory and gastrointestinal systems. Tolerance developed in only 20% of the patients. High sIgE (>0.15 IU) was demonstrated only in 75% of those in which it was examined. Sixteen patients performed oral sesame food challenge which was found positive in 88%. No correlation was found between the size of SPT and the level of in vitro sesame IgE antibodies, the outcome of OC results, and the development of tolerance to sesame. In conclusion, SFA tends to appear early in life, but unlike cow's milk and egg allergy, persists in 80% of the cases. Typical reactions combined with positive sesame SPT are reliable for diagnosis. PMID- 17346303 TI - Low prevalence of Helicobacteraceae in gall-stone disease and gall-bladder carcinoma in the German population. AB - Colonisation of the hepatobiliary system with bile-resistant Helicobacter spp. has been proposed as a novel risk-factor in the pathogenesis of gall-bladder carcinoma (GBC). There are reports that biliary Helicobacter colonisation is frequent in countries with a high incidence of gall-bladder carcinoma. However, the prevalence of Helicobacteraceae in the gall-bladders of patients with GBC in Germany, a region with a low incidence of GBC, is unknown. Therefore, gall bladder tissue from 99 patients who had undergone cholecystectomy was tested, including 57 cases of gall-stone disease (GSD), 20 cases of GBC, and 22 control patients. The presence of Helicobacter spp. was investigated by culture, immunohistochemistry and a group-specific PCR targeting the 16S rRNA gene of all currently known Helicobacteraceae. Of the 99 cases investigated, only one patient with GSD was PCR-positive for Helicobacteraceae. For this individual, sequence analysis of the 16S rRNA gene showed that it had homology closest to the 16S rRNA sequence of Helicobacter ganmani. Helicobacteraceae were not detected by culture or immunohistochemistry. The low prevalence of Helicobacteraceae in the gall bladders investigated suggests that Helicobacteraceae do not play a predominant role in the pathogenesis of GSD and GBC in the German population. The low prevalence could be a possible explanation for a relatively low incidence of GBC in the German population, despite the fact that GSD, the major risk-factor for GBC, is highly prevalent. PMID- 17346304 TI - A randomized, double-blind, placebo-controlled study of venlafaxine XR in out patients with tension-type headache. AB - The aim of this study was to evaluate in a double-blind, randomized, placebo controlled study the safety and efficacy of venlafaxine extended release (XR) in the prophylactic treatment of out-patients with tension-type headache (TTH) and no current depression or anxiety disorders. Sixty neurology and headache clinic out-patients meeting the International Headache Society diagnostic criteria for TTH were treated with venlafaxine XR (150 mg/day, n = 34) or placebo (n = 26) for 12 weeks. The primary efficacy variable was the decline in number of days with headache. At end-point, the venlafaxine XR group had a significantly greater decrease in the number of days with headache compared with placebo (P = 0.05). Differences with regard to secondary efficacy variables where not significant. The number needed to treat for responders (>or=50% reduction in days with headache) was 3.48. Six patients in the venlafaxine XR group interrupted therapy due to adverse events, while no patients in the placebo group did so for the same reason. The number needed to harm was 5.58. This study provides preliminary evidence for the efficacy and safety of venlafaxine XR 150 mg/day in reducing the number of days with TTH. PMID- 17346305 TI - Developing a research agenda in headache service delivery: proceed with caution. AB - With a recognition that the management of headache remains far from ideal, there may be more immediate potential to reduce the burden of illness from developments in the delivery of headache services. There is a paucity of evidence in this area and a danger that an expanding research agenda will be dominated by inappropriate methodological frameworks that have been so successful in developing medical treatments. The prevailing scientific methods are underpinned by statistical approaches that are aggregative in nature and assume independence of system elements, an approach that may have limited utility in the analysis of complex systems such as headache care delivery. This review calls for a shift in headache research resources to organizational development and briefly outlines alternative methodological considerations. PMID- 17346306 TI - Migraine and coronary heart disease mortality: a prospective cohort study. AB - A recent population-based prospective study reported that in women, migraine with aura (MA), but not migraine without aura (MoA), was associated with increased risk of coronary heart disease events (CHD). We sought to confirm this association in an Australian population-based cohort of older men and women (n = 2331, aged 49-97 years). We defined MA and MoA from face-to-face interview using International Headache Society criteria. Over a mean 6-year follow-up, 30 women (2.8%) and 30 men (4.4%) without any prior CHD history died from CHD-related causes. In women, a history of MA was associated with a non-significant twofold higher risk of CHD death (age-adjusted relative risk 2.2, 95% confidence interval 0.8, 5.8, P = 0.11), which remained similar after adjustment for cardiovascular risk factors. There were no CHD deaths in men with a history of migraine. Our findings support reports that in women, MA, but not MoA, may be associated with increased risk of CHD. PMID- 17346307 TI - TLR signalling and phagosome maturation: an alternative viewpoint. PMID- 17346308 TI - Bacteriophage-encoded toxins: the lambda-holin protein causes caspase-independent non-apoptotic cell death of eukaryotic cells. AB - The bacteriophage-encoded holin proteins are known to promote bacterial cell lysis by forming lesions within the cytoplasmic membrane. Recently, we have shown that the bacteriophage lambda-holin protein exerts cytotoxic activity also in eukaryotic cells accounting for a reduced tumour growth in vivo. In order to elucidate the mechanisms of lambda-holin-induced mammalian cell death, detailed biochemical and morphological analyses were performed. Colocalization analyses by subcellular fractionation and organelle-specific fluorescence immunocytochemistry indicated the presence of the lambda-holin protein in the endoplasmic reticulum and in mitochondria. Functional studies using the mitochondria-specific fluorochrome JC-1 demonstrated a loss of mitochondrial transmembrane potential in response to lambda-holin expression. Morphologically, these cells exhibited unfragmented nuclei but severe cytoplasmic vacuolization representing signs of oncosis/necrosis rather than apoptosis. Consistently, Western blot analyses indicated neither an activation of effector caspases 3 and 7 nor cleavage of the respective substrate poly(ADP-ribose) polymerase (PARP) in an apoptosis-specific manner. These findings suggest that the lambda-holin protein mediates a caspase independent non-apoptotic mode of cell death. PMID- 17346309 TI - Rhoptries are major players in Toxoplasma gondii invasion and host cell interaction. AB - Rhoptries are unique secretory organelles shared by all Apicomplexan invasive stages. They are exocytosed upon host cell invasion and their contents are involved in creating the moving junction that propels the parasite in the cell and in building the parasitophorous vacuole in which the parasite will develop. In addition, some rhoptry proteins are targeted to the host cell nucleus. The array of roles played by these organelles has considerably expanded in the recent years, making them a major clue to the understanding of the early interaction between these parasites and their host. Yet, our knowledge on these organelles is still very poor and much has to be done before we get a clear view of the part they play in Apicomplexan biology. PMID- 17346310 TI - Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection. AB - Anaplasma phagocytophilum, an obligate intracellular pathogen that persists within polymorphonuclear leucocytes, is the second most common tick-borne agent in North America. We now show that infection of a promyelocytic cell line and neutrophils with A. phagocytophilum results in pathogen-specific tyrosine phosphorylation of ROCK1. Phosphorylation is associated with PSGL-1 and Syk, because PSGL-1 blocking antibodies and siRNA targeting Syk interfere with ROCK1 phosphorylation in A. phagocytophilum-infected cells. Knockdown of either Syk or ROCK1 also markedly impaired A. phagocytophilum infection. These data demonstrate a role for A. phagocytophilum-mediated ROCK1 phosphorylation in infection, and suggests that inhibiting this pathway may lead to new, non-antibiotic strategies to treat human granulocytic anaplasmosis. PMID- 17346311 TI - Phagocytosis and persistence of Helicobacter pylori. AB - Helicobacter pylori is a spiral-shaped, flagellated, microaerophilic Gram negative bacterium that colonizes the gastric epithelium of humans. All persons infected with H. pylori have gastritis, and some will develop severe disease such as peptic ulcers or gastric cancer. A characteristic feature of this infection is the pronounced accumulation of phagocytes, particularly neutrophils, in the gastric mucosa. H. pylori thrives in a phagocyte-rich environment, and we describe here how this organism uses an array of novel virulence factors to manipulate chemotaxis, phagocytosis, membrane trafficking and the respiratory burst as a means to evade elimination by the innate immune response. PMID- 17346312 TI - Specific interaction of HeLa cell proteins with coxsackievirus B3 3'UTR: La autoantigen binds the 3' and 5'UTR independently of the poly(A) tail. AB - Coxsackievirus B3 (CVB3) is a positive, single-stranded RNA virus. The secondary structure of the 3' untranslated region (3'UTR) of CVB3 RNA consists of three stem-loops and is followed by a poly(A) tail sequence. These stem-loop structures have been suggested to participate in the regulation of viral replication through interaction with cellular proteins that are yet to be identified. In this study, by competitive UV cross-linking using mutated 3'UTR probes we have demonstrated that the poly(A) tail is essential for promoting HeLa cell protein interactions with the 3'UTR because deletion of this sequence abolished most of the protein interactions. Unexpectedly, mutations that disrupted the tertiary loop-loop interactions without affecting the stem-loops did not apparently affect these protein interactions, indicating that secondary structure rather than the high order structure may play a major role in recruiting these RNA binding proteins. Among the observed 3'UTR RNA binding proteins, we have confirmed a 52 kDa protein as the human La autoantigen by using purified recombinant protein and a polyclonal La antibody. This protein can interact with both the 3' and 5'UTRs independently of the poly(A) tail. Further analysis by two-stage UV cross linking, we found that the 3' and 5'UTR sequences may share the same binding site on the La protein. PMID- 17346313 TI - Localization of protein kinase C epsilon to macrophage vacuoles perforated by Listeria monocytogenes cytolysin. AB - Three proteins secreted by Listeria monocytogenes facilitate escape from macrophage vacuoles: the cholesterol-dependent cytolysin listeriolysin O (LLO), a phosphoinositide-specific phospholipase C (PI-PLC) and a broad-range phospholipase C (PC-PLC). LLO and PI-PLC can activate several members of the protein kinase C (PKC) family during infection. PKCepsilon is a novel PKC that contributes to macrophage activation, defence against bacterial infection, and phagocytosis; however, a role for PKCepsilon in Lm infections has not been described. To study PKCepsilon dynamics, PKCepsilon-YFP chimeras were visualized in macrophages during Lm infection. PKCepsilon-YFP was recruited to forming vacuoles during macrophage phagocytosis of Lm and again later to fully formed Lm vacuoles. The PKCepsilon-YFP localization to the fully formed Lm vacuole was LLO dependent but independent of PI-PLC or PC-PLC. PKCepsilon-YFP recruitment often followed LLO perforation of the membrane, as indicated by localization of PKCepsilon-YFP to Lm vacuoles after they released small fluorescent dyes into the cytoplasm. PKCepsilon-YFP recruitment to vesicles also followed phagocytosis of LLO-containing liposomes or osmotic lysis of endocytic vesicles, indicating that vacuole perforation by LLO was the chief cause of the PKCepsilon response. These studies implicate PKCepsilon in a cellular mechanism for recognizing damaged membranous organelles, including the disrupted vacuoles created when Lm escapes into cytoplasm. PMID- 17346314 TI - Differential susceptibility of mitogen-activated protein kinase pathway mutants to oxidative-mediated killing by phagocytes in the fungal pathogen Candida albicans. AB - The role of four mitogen-activated protein (MAP) kinase pathways in the survival of Candida albicans following infection of human phagocytes has been addressed through the analysis of mutants defective in their respective MAP kinase. While the contribution of the cell integrity (Mkc1-mediated) or mating (Cek2-mediated) pathways is relatively minor to survival, clear and opposite effects were observed for cek1 and hog1 mutants, despite the fact that these two MAP kinases are important virulence determinants in the mouse model of experimental infection. The Cek1-mediated pathway is involved in sensitivity to phagocyte mediated killing, while the HOG pathway contributes to the survival of the fungal cells in this interaction. Furthermore, reporter genes have been developed to quantify oxidative and nitrosative stress. hog1 mutants show an oxidative and nitrosative stress response augmented - albeit non-protective - when challenged with oxidants and NO donors in vitro or phagocytic cells (macrophages, neutrophils and the myelomonocytic cell line HL-60), suggesting this as the cause of their reduced virulence in the murine model of infection. These data have important consequences for the development of novel antifungal therapies to combat against fungal infection. PMID- 17346315 TI - HtpG, the Porphyromonas gingivalis HSP-90 homologue, induces the chemokine CXCL8 in human monocytic and microvascular vein endothelial cells. AB - CXCL8 (interlukin 8, IL-8) has a diverse spectrum of biological activities including T cell, neutrophil and basophil chemotactic properties. It is produced by a wide variety of cell types and plays a significant role in the initiation of the acute inflammatory response. During inflammation, CXCL8 attracts and activates leukocytes at the site of infection leading to leukocyte infiltration, which can lead to tissue damage. Porphyromonas gingivalis, an aetiological agent of periodontitis, induces production of CXCL8 from several types of cells via its LPS and outer membrane proteins. Bacterial chaperones elicit a strong pro inflammatory response in cells of the innate immune system. In P. gingivalis the htpG gene codes for the homologue of human Hsp90, a chaperone that associates with transcription factors, hormone receptors and protein kinases, affecting signal transduction pathways. CXCL8 mRNA and CXCL8 protein production was induced in monocytic/human microvascular vein endothelial cells treated with P. gingivalis cells or rHtpG protein. Blocking of receptors CD91 and TLR4 reduced the production of CXCL8 by rHtpG either using receptor-specific antibody or by siRNA silencing. Pre-incubation of P. gingivalis rHtpG preparations with human anti-HtpG significantly inhibited CXCL8 production. A P. gingivalis HtpG disruption mutant also induced less CXCL8 mRNA and protein. These results suggest that P. gingivalis HtpG might be involved in CXCL8-mediated immunopathogenesis. PMID- 17346316 TI - Screening tools for depressed mood after childbirth in UK-based South Asian women: a systematic review. AB - AIM: This paper is a report of a systematic review to answer the question: what is the relevance, acceptability, validity and effectiveness of tools designed to screen for postnatal depressed mood for South Asian women living in the UK? BACKGROUND: Standard methods to screen women for postnatal depressed mood were developed with Caucasian populations. This study reviews postnatal screening tools adapted or developed for United Kingdom-based South Asian women. METHOD: A structured systematic review of English language studies initially was completed between 1980 and May 2003, and later updated to January 2005. The review was based on an a priori search strategy with inclusion and exclusion criteria and analysis included a quality assessment tool. Findings were tabulated against criteria for acceptability and effectiveness of diagnostic tools. RESULTS: Seven papers were included in the review. None addressed all preset quality criteria. Four papers among them reported on translations of two existing tools (Edinburgh Postnatal Depression Scale and General Household Questionnaire). Two new tools were reported between the remaining three papers (Punjabi Postnatal Depression Scale and 'Doop Chaon'. Doop Chaon is a visual tool. The other tools used either Bengali or Punjabi, based on written scales. The General Household Questionnaire did not appear to be appropriate for this population. None of the studies were rigorous enough to demonstrate generalizable sensitivity or specificity. Qualitative data indicated that women preferred face-to-face interviews to self complete questionnaires. CONCLUSIONS: None of the tools are currently sufficiently evaluated for clinical practice. Questions are raised specifically about use of language-based tools to measure postnatal depressed mood in this population and about the extent to which focused interviews could be used as an alternative for specific sub-sections of population groups. PMID- 17346317 TI - Older caregivers' coping strategies and sense of coherence in relation to quality of life. AB - AIM: This paper reports a study to investigate coping strategies and sense of coherence in relation to gender, the extent of care, caregiving activities and health-related quality of life in a population-based sample of caregivers aged 75 and over. BACKGROUND: Caring for another person can be stressful both emotionally, and caregiver burden may affect quality of life in a negative way for the carer. Caregivers' experience of burden may depend on for example, the behaviour of the person cared for, their own health and their sense of coherence. Older people take a great part of caregiving responsibility and thus understanding of their strain and coping is required. METHODS: A postal survey was carried out in 2001 with 171 informal caregivers, aged 75 or older. The response rate was 47%. The questionnaire included the Short-Form 12, Carer's Assessment of Managing Index, and Sense of Coherence instrument. RESULTS: Almost 70% of caregivers provided help every day. Higher health-related quality of life was predicted by using self-sustaining coping strategies and by high sense of coherence. Poor economic situation and demanding social and practical support predicted low scores. CONCLUSION: These findings could help identify those at risk of low quality of life due to caregiving, dysfunctional coping or lack of information about care. Early intervention, including education about alternative coping strategies and practical information, might allow caregivers better possibilities to continue caring with less negative effects on their lives. PMID- 17346318 TI - Patients' conceptions of how the spiritual dimension is addressed in mental health care: a qualitative study. AB - AIM: This paper reports a study to describe patients' conceptions of how the spiritual dimension is addressed in mental health care. BACKGROUND: Spirituality is a broad concept, and is highly subjective, multidimensional and difficult to define. Spirituality and religiousness are two separate concepts but have several common features. In mental health care, it is essential that nursing care be built on a holistic view, and the spiritual dimension has an important function in nursing care. The notion of spirituality is full of nuances, and in a multi cultural society patients express their spirituality in different ways. METHOD: Data were collected by interviewing 12 strategically selected patients in mental health care and analysed according to a qualitative method inspired by the phenomenographic approach. The data were collected in 2003 in Sweden. FINDINGS: Three descriptive categories emerged: patients wish to have their spiritual needs addressed; patients must see to it that their spiritual needs are addressed; patients lack confidence in nurses with regard to discussing spirituality. The findings show that patients actively sought the assistance of nurses to meet their spiritual needs. They turned their thoughts inwards and found community with other patients, while nurses often avoided addressing the spiritual dimension. CONCLUSION: Nurses should work actively to seek new knowledge about how they can address patients' spiritual needs. It is also important that there be scope for discussing and reflecting on spiritual questions at the workplace. Additional research is needed to explore how knowledge about spirituality should be implemented in mental health care and nursing education. PMID- 17346319 TI - An exploratory study of Chinese older people's perceptions of privacy in residential care homes. AB - AIM: This paper reports a study to examine Chinese older people's perceptions of privacy in residential care homes. BACKGROUND: With increasing numbers of older people moving into residential care homes in Hong Kong, the emphasis on providing high quality of care is paramount. Yet, studies have identified the poor quality of psychosocial care provided in these homes, particularly the lack of attention given to promoting a sense of privacy. While privacy is a fundamental principle of gerontological care, little is known older people's perceptions of privacy in residential care practices. This lack of understanding makes it difficult to know how to provide appropriate care to this population. METHOD: A descriptive qualitative study was conducted in 2005 with a purposive sample of 20 informants from four residential care homes in Hong Kong. In-depth interviews were used to collect the data, which were analysed using content analysis. RESULTS: Most informants perceived that privacy was unnecessary and not a pre-requisite in residential living. They had seemingly accepted the expectations of home life, with its emphasis on unity, harmony and meeting the collective needs of the majority rather than focusing on their individual needs. Informants also described the enjoyment of communal living and 'living together'. While at first privacy was perceived as not necessary, further prompting identified that informants used own efforts to support their privacy. There were also day-to-day circumstances/activities in homes where privacy was violated. CONCLUSION: The emphasis in Chinese culture on the importance of maintaining balance and harmony inevitably shaped participants' perceptions of what privacy meant to them. The findings will inform the development of culturally-sensitive care practices to support Chinese older people's privacy in residential care settings. PMID- 17346320 TI - Cancer survivors' experience of time: time disruption and time appropriation. AB - AIM: This paper reports a study to explore how cancer survivors talk about, experience and manage time in everyday life. BACKGROUND: There is an increasing interest in specific physical and psychosocial aspects of life after cancer diagnosis and treatment, but hardly any research follows cancer survivors over time to explore how perceptions and experiences change. METHODS: An exploratory study was carried out in 2002-2004 with a purposive sample of adults who had experienced various forms of cancer. Data collection included 9 weeks of participant observation at a Cancer Rehabilitation Centre and ethnographic interviews with 23 informants. Ten men and 13 women were interviewed twice: 2 weeks after their stay and 18 months later. FINDINGS: Data were analysed from a culture-analytical perspective. Three main themes regarding the survivors' handling and perception of time were found: (1) cancer disrupts time and life; (2) awareness of time increases, time is verbalized and reflected; and (3) the informants appropriate time. A diagnosis of cancer, even for a survivor, means a confrontation with death. It means a disruption of continuous clock and calendar time. Survivors appropriate time, and prioritize how and with whom they want to spend their time. CONCLUSION: With an increasing number of people being cured following a cancer diagnosis, nurses and oncology nurse specialists who work with cancer survivors must be aware of the fact that time is a central theme in understanding cancer survivors' lives, and they must know how to guide these survivors in their new lives and take care of their well-being. PMID- 17346321 TI - Nurses' experiences of caring for families with relatives in intensive care units. AB - AIM: This paper reports an exploratory study of nurses' experiences of caring for families who have relatives in adult intensive care units. BACKGROUND: The admission of a critically ill patient into adult intensive care is universally accepted as a crisis for both patients and their families. Family members of critically ill people may experience emotional turmoil and therefore have many needs throughout the course of the relative's illness. It has been identified that nurses are best placed to meet families' needs. Whilst there is a substantial evidence base associated with family needs, little is known about nurses' experiences of caring for these families. METHOD: Interviews, informed by Heideggerian philosophy, were conducted with a purposive sample of 12 Registered Nurses working in an adult intensive care unit. Interview transcripts were analysed using Colaizzi's framework. The data were collected in Autumn 2005. FINDINGS: Participants' experiences were categorized into the following themes: defining the nurse's role, role expectations and role conflict. Participants reported lack of confidence, doubts about their professional competence and conflicts between their professional and personal self. These experiences were linked to participants' expectations and self-imposed standards. CONCLUSION: Registered Nurses caring for families who have relatives in adult intensive care units face a fundamental conflict both between role expectations and patient care and between professional ideals and being a human. This not only highlights a disparity between nurses everyday family care practice and the underpinning theories but also may contribute to occupational stress. PMID- 17346322 TI - Oral care in cancer nursing: nurses' knowledge and education. AB - AIM: This paper reports a study of nurses' knowledge and education in relation to oral care and oral health assessment for patients undergoing cancer treatment. BACKGROUND: Studies suggest that ritualistic practice of oral care occurs and that nurses dislike providing this type of care. Inadequate knowledge and education of oral care among nurses have also been revealed, as well as a lack of involvement of dentists in this aspect of nurse education. METHOD: In 2003, an oral care questionnaire was administered to a non-random sample of 100 general and cancer nurses employed in an oncology centre, with a response rate of 72%. Information was collected on knowledge and education in relation to oral care, management of oral care, and influences on nurses' knowledge of oral care and performance of oral care. The questionnaire was tested for content validity by a panel of experts and modified accordingly. Reliability of the questionnaire subscales varied from a Cronbach's alpha of 0.56-0.82. Internal consistency for the total knowledge of oral care scale obtained an alpha of 0.93. FINDINGS: Data indicated that respondents had not had substantial oral care education during preregistration education, and their knowledge of oral health status, signs and symptoms of abnormalities was inadequate. Nurses placed a high degree of priority on oral care for patients with cancer. Respondents had also received insufficient support from hospital dentists for patients undergoing cancer treatment. CONCLUSION: Nurses require more education if they are to manage the oral care of patients with cancer effectively, and further research is needed into the actual practice of oral care for patients with cancer. PMID- 17346323 TI - Establishing a super-link system: spinal cord injury rehabilitation nursing. AB - AIM: This paper reports a study to identify the needs of clients with spinal cord injury and their family/carers during rehabilitation, and the strategies used by rehabilitation nurses to meet those needs. BACKGROUND: In Taiwan, spinal cord injury is a major problem with financial implications for the state and major bio psycho-social and spiritual implications for the individual. Rehabilitation nurses do not have an appropriate nursing theory to guide their care. METHODS: Using a grounded theory approach, data were collected from October 2002 to March 2003 in a rehabilitation hospital in Taiwan by means of interviews, participant observations and documentary resources; analysis was an interrelated process. A total of 39 interviews was carried out with 31 individuals, including eight rehabilitation nurses, one nurse supervisor, seven clients with tetraplegia, eight with paraplegia and seven family/carers. There were 18 participant observations. Data were analysed using a multi-step analytic procedure, based on the works of Glaser, Charmaz, and Strauss and Corbin. FINDINGS: The core category, 'establishing a super-link system', explained the complex structure of interactions observed during the investigation and the importance of developing a middle-range theory entitled the 'Super-Link System Theory'. This theory includes the following four links: 'linking to client', 'linking to family/carer', 'linking to interdisciplinary rehabilitation team' and 'linking to community'. CONCLUSION: This Super-Link System Theory will help rehabilitation nurses to organize their thinking about spinal cord injury rehabilitation nursing, to transfer their thinking into practice by making links effective, and to promote their professional position in the interdisciplinary rehabilitation team. PMID- 17346324 TI - Postoperative education and pain in patients with inguinal hernia. AB - AIM: This paper reports a study to investigate whether education can reduce postoperative pain in patients operated on for inguinal hernia. BACKGROUND: Operation for inguinal hernia is a frequent, elective procedure. Studies indicate that 20% of patients operated on for this condition still have moderate to severe pain on the sixth postoperative day. They also show a connection between postoperative pain and time to return to work, inconvenience relating to recreation and work and development of chronic pain. METHOD: The design was a randomized, clinically controlled, single-blinded study, carried out in 2002 2003. The intervention group received education on discharge from hospital, followed by a telephone interview on the second postoperative day. The control group was given the usual routine information. In a questionnaire, patients ranked their pain on a 100-mm Visual Analogue Scale on the first, third and seventh postoperative days. RESULTS: The study included 234 consecutive patients. The baseline characteristics for the intervention and the control group were identical. Pain was analysed as the difference in Visual Analogue Scale scores immediately preoperatively and on the chosen days postoperatively. No difference was found for pain while resting, pain when moving on the first and third postoperative day and time to return to work. Statistically, there was a significant difference (P = 0.028) between the groups for pain when moving on the seventh postoperative day. The estimated mean difference was 7 mm (95% confidence interval 0.7-13.1 mm). CONCLUSIONS: In patients operated on for inguinal hernia, postoperative education and a telephone interview have no effect on postoperative pain while resting and time to return to work. The effect on pain while moving was slight. There is no reason to change standard practice. PMID- 17346325 TI - Living with uncertainty: concept advancement. AB - AIM: This paper reports a study to demonstrate how the scientific understanding of the concept of uncertainty was advanced through a phenomenological study of living with uncertainty. BACKGROUND: Techniques for concept analysis have evolved to subsume strategies for advancing a concept towards greater clarity and utility for research and practice. Recently, it has been argued that a clear delineation of techniques for concept analysis as separate and distinct from techniques of concept advancement is warranted. This article applies such delineated processes to demonstrate the advancement of the concept of uncertainty. METHOD: Concept analysis was used to establish an integrated understanding of the state of the science. Gaps in understanding were carefully analysed, resulting in the research question guiding the next phase of concept advancement: what is the nature of the lived experience of uncertainty? A phenomenological investigation of the experience of uncertainty among family caregivers was conducted. Then, using methods of template comparison, the conceptual attributes identified through the phenomenological study were compared and contrasted with the theoretical definition derived through concept analysis. Finally, a new conceptual definition of higher order abstraction, with greater pragmatic utility, was derived. FINDINGS: Uncertainty is rooted in the individual's perception of outcomes or meaning of a situation. Such perceptions challenge one's sense of confidence and/or control to yield varied types and modes of uncertainty. Uncertainty is present oriented. Both cognitive and precognitive ways of knowing are influential in ascribing meaning, anticipating outcomes and adapting strategies. CONCLUSIONS: One's sense of confidence and sense of control are primary essences that determine the nature of the experience of uncertainty. The experience of living with uncertainty is dynamic, with fluctuations in the types and modes of uncertainty in response to precognitive and cognitive ways of knowing. Probabilistic paradigms preclude existential and situational modes of uncertainty for which probabilities cannot be appreciated. PMID- 17346330 TI - Microsatellite analysis of Damask rose (Rosa damascena Mill.) accessions from various regions in Iran reveals multiple genotypes. AB - BACKGROUND: Damask roses (Rosa damascena Mill.) are mainly used for essential oil production. Previous studies have indicated that all production material in Bulgaria and Turkey consists of only one genotype. Nine polymorphic microsatellite markers were used to analyze the genetic diversity of 40 accessions of R. damascena collected across major and minor rose oil production areas in Iran. RESULTS: All microsatellite markers showed a high level of polymorphism (5-15 alleles per microsatellite marker, with an average of 9.11 alleles per locus). Cluster analysis of genetic similarities revealed that these microsatellites identified a total of nine different genotypes. The genotype from Isfahan province, which is the major production area, was by far the most common genotype (27/40 accessions). It was identical to the Bulgarian genotype. Other genotypes (each represented by 1-4 accessions) were collected from minor production areas in several provinces, notably in the mountainous Northwest of Iran. CONCLUSION: This is the first study that uncovered genetic diversity within Damask rose. Our results will guide new collection activities to establish larger collections and manage the Iranian Damask rose genetic resources. The genotypes identified here may be directly useful for breeding. PMID- 17346331 TI - Orthology prediction at scalable resolution by phylogenetic tree analysis. AB - BACKGROUND: Orthology is one of the cornerstones of gene function prediction. Dividing the phylogenetic relations between genes into either orthologs or paralogs is however an oversimplification. Already in two-species gene phylogenies, the complicated, non-transitive nature of phylogenetic relations results in inparalogs and outparalogs. For situations with more than two species we lack semantics to specifically describe the phylogenetic relations, let alone to exploit them. Published procedures to extract orthologous groups from phylogenetic trees do not allow identification of orthology at various levels of resolution, nor do they document the relations between the orthologous groups. RESULTS: We introduce "levels of orthology" to describe the multi-level nature of gene relations. This is implemented in a program LOFT (Levels of Orthology From Trees) that assigns hierarchical orthology numbers to genes based on a phylogenetic tree. To decide upon speciation and gene duplication events in a tree LOFT can be instructed either to perform classical species-tree reconciliation or to use the species overlap between partitions in the tree. The hierarchical orthology numbers assigned by LOFT effectively summarize the phylogenetic relations between genes. The resulting high-resolution orthologous groups are depicted in colour, facilitating visual inspection of (large) trees. A benchmark for orthology prediction, that takes into account the varying levels of orthology between genes, shows that the phylogeny-based high-resolution orthology assignments made by LOFT are reliable. CONCLUSION: The "levels of orthology" concept offers high resolution, reliable orthology, while preserving the relations between orthologous groups. A Windows as well as a preliminary Java version of LOFT is available from the LOFT website http://www.cmbi.ru.nl/LOFT. PMID- 17346332 TI - Caesarean section in a semi-rural hospital in Northern Namibia. AB - BACKGROUND: Increasing caesarean sections rates (CSR) are a major public health concern and the prevention of the first caesarean section, which often leads to repeat operations, is an important issue. Analyzing caesarean sections can help to identify factors associated with variations in CSR and help to assess the quality of clinical care. METHODS: In a retrospective observational study, during a two year period, indications of 576 caesarean sections were analyzed using intra-operative internal pelvimetry and a record keeping system in a semi-rural hospital in Northern Namibia. RESULTS: Most caesarean sections were done for dystocia (34%) followed by repeat caesarean section (31%). The true conjugate (distance between the promontorium to mid pubic bone) was significantly smaller in these recurrent indication groups when compared to non recurrent indications. CONCLUSION: In this rural hospital the introduction of Delee Pelvimetry and a caesarean section record keeping system was found to be a simple and cheap method to analyse indications for caesarean sections, which may help in reducing unnecessary caesarean sections. PMID- 17346333 TI - Depression and anxiety, an indicated prevention (DIP) protocol in homes for the elderly: feasibility and (cost) effectiveness of a stepped care programme. AB - BACKGROUND: Depressive and anxiety disorders are a very common, serious and underdetected problem in homes for the elderly. Elderly persons in residential homes are at high risk for developing major depressive and anxiety disorders, and, therefore, deserve attention with regard to prevention. METHODS/DESIGN: This protocol describes a randomised trial on the feasibility and (cost) effectiveness of a stepped-care programme for prevention of depressive and anxiety disorders in homes for the elderly. The main outcome measure is the incidence of depressive and anxiety disorder in one year with a two years follow up. Secondary outcomes are symptoms of depression and anxiety, quality of life, direct health care costs and satisfaction with treatment. DISCUSSION: The number of studies examining the effects of preventive interventions on the incidence of mental disorders in the elderly population is very small. However, indicated prevention by means of a stepped-care programme seems to be an important option for decreasing the burden of illness for residents and their caregivers. This study contributes to the body of knowledge in this field. Positive effects may contribute to further use and development of tailored, (cost-) effective and easy to use interventions in a preventive stepped-care programme. PMID- 17346334 TI - High mobility group box-1 protein in patients with suspected community-acquired infections and sepsis: a prospective study. AB - INTRODUCTION: Sepsis is a serious condition with a significant morbidity and mortality. New insight into the immunopathogenesis of sepsis could promote the development of new strategies for diagnosis and therapy. High mobility group box 1 protein (HMGB1) has been known for many years as a nuclear chromosomal protein. Its role as a pro-inflammatory cytokine in sepsis and rheumatoid arthritis has been described recently. The aim of our study was to evaluate HMGB1 as a molecular marker in patients with community-acquired infections. METHODS: Patients suspected of having infections/sepsis and admitted to a department of internal medicine were included in the study in a prospective manner. Demographic data, comorbidity, routine biochemistry, microbiological data, infection focus, severity score, and mortality on day 28 were recorded. Plasma and serum were sampled at the time of admission. HMGB1 levels were measured with a commercially available enzyme-linked immunosorbent assay (ELISA). Procalcitonin levels were measured with a TRACE (time-resolved amplified cryptate emission) assay. Lipopolysaccharide-binding protein and interleukin-6 were measured with a chemiluminiscent immunometric assay. Soluble haemoglobin scavenger receptor (sCD163) levels were measured with an in-house ELISA. RESULTS: One hundred and ninety-four patients were included in the study. Levels of HMGB1 are presented as medians and interquartile ranges: healthy controls (0.77 ng/ml, 0.6 to 1.46), non infected patients (1.54 ng/ml, 0.79 to 2.88), infected patients without systemic inflammatory response syndrome (2.41 ng/ml, 0.63 to 3.44), patients with sepsis (2.24 ng/ml, 1.30 to 3.75), and patients with severe sepsis (2.18 ng/ml, 0.91 to 3.85). In a receiver operator characteristic curve analysis discriminating between non-infected patients and all infected patients, the area under the curve for HMGB1 was 0.59 (P < 0.0001). HMGB1 correlated only weakly to levels of white blood cell count, neutrophils, C-reactive protein, interleukin-6, procalcitonin, and lipopolysaccharide-binding protein (P < 0.001). HMGB1 did not correlate to sCD163. CONCLUSION: In a cohort of patients with suspected community-acquired infections and sepsis, HMGB1 levels were statistically significantly higher in patients compared to the healthy controls. There was no statistically significant difference between the infected and the non-infected patients. Levels of HMGB1 correlated only very weakly to other pro-inflammatory markers and did not correlate to the anti-inflammatory marker sCD163. PMID- 17346335 TI - Perimenopausal contraception in Turkish women: A cross-sectional study. AB - BACKGROUND: Epidemiologic research has shown that perimenopausal contraception is an important medical issue, because women during the perimenopause still need effective contraception. The objective of the study was to assess the contraceptive choices of perimenopausal Turkish women. METHODS: This is a descriptive cross-sectional study that in a non - random fashion recruited 202 perimenopausal and naturally menopausal women who lived in a suburban area of Istanbul. Women who took part were aged between 45-59 years old. Chief database used to identify the suitable participants in the district. Subjects who voluntarily participated in the study were interviewed in their homes by the researcher. The analysis of the data was evaluated using percentages. RESULTS: The percentage of sexually active women among the participants was 87.6%. A large majority - 80.2% - of the participants did not have any idea of when they should bring contraception to an end. The method most commonly used was withdrawal (Coitus Interruptus), represented by 38.8%. In regard to the participants' choices of medical contraception, those being utilized were the IUD (24.3%), tubal sterilization (8.9%), condom (5.9%) and COC (6.4%). Additionally, 18% of women used other traditional methods including vaginal lavage, vaginal aspirin, and even inserting a small sponge presoaked with fresh lemon juice or cola deep into the vagina. Among the perimenopausal women who participated, the IUD was the most popular and appropriate contraceptive method. CONCLUSION: Most perimenopausal Turkish women are still using traditional methods and women's knowledge about contraception in the menopausal stages is very limited. Health professionals should provide information about perimenopausal contraception. PMID- 17346336 TI - Clinical decision support tools: analysis of online drug information databases. AB - BACKGROUND: Online drug information databases are used to assist in enhancing clinical decision support. However, the choice of which online database to consult, purchase or subscribe to is likely made based on subjective elements such as history of use, familiarity, or availability during professional training. The purpose of this study was to evaluate clinical decision support tools for drug information by systematically comparing the most commonly used online drug information databases. METHODS: Five commercially available and two freely available online drug information databases were evaluated according to scope (presence or absence of answer), completeness (the comprehensiveness of the answers), and ease of use. Additionally, a composite score integrating all three criteria was utilized. Fifteen weighted categories comprised of 158 questions were used to conduct the analysis. Descriptive statistics and Chi-square were used to summarize the evaluation components and make comparisons between databases. Scheffe's multiple comparison procedure was used to determine statistically different scope and completeness scores. The composite score was subjected to sensitivity analysis to investigate the effect of the choice of percentages for scope and completeness. RESULTS: The rankings for the databases from highest to lowest, based on composite scores were Clinical Pharmacology, Micromedex, Lexi-Comp Online, Facts & Comparisons 4.0, Epocrates Online Premium, RxList.com, and Epocrates Online Free. Differences in scope produced three statistical groupings with Group 1 (best) performers being: Clinical Pharmacology, Micromedex, Facts & Comparisons 4.0, Lexi-Comp Online, Group 2: Epocrates Premium and RxList.com and Group 3: Epocrates Free (p < 0.05). Completeness scores were similarly stratified. Collapsing the databases into two groups by access (subscription or free), showed the subscription databases performed better than the free databases in the measured criteria (p < 0.001). CONCLUSION: Online drug information databases, which belong to clinical decision support, vary in their ability to answer questions across a range of categories. PMID- 17346337 TI - The value of predicting restriction of fetal growth and compromise of its wellbeing: Systematic quantitative overviews (meta-analysis) of test accuracy literature. AB - BACKGROUND: Restriction of fetal growth and compromise of fetal wellbeing remain significant causes of perinatal death and childhood disability. At present, there is a lack of scientific consensus about the best strategies for predicting these conditions before birth. Therefore, there is uncertainty about the best management of pregnant women who might have a growth restricted baby. This is likely to be due to a dearth of clear collated information from individual research studies drawn from different sources on this subject. METHODS/DESIGN: A series of systematic reviews and meta-analyses will be undertaken to determine, among pregnant women, the accuracy of various tests to predict and/or diagnose fetal growth restriction and compromise of fetal wellbeing. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Independent reviewers will select studies, extract data and assess study quality according to established criteria. Language restrictions will not be applied. Data synthesis will involve meta-analysis (where appropriate), exploration of heterogeneity and publication bias. DISCUSSION: The project will collate and synthesise the available evidence regarding the value of the tests for predicting restriction of fetal growth and compromise of fetal wellbeing. The systematic overviews will assess the quality of the available evidence, estimate the magnitude of potential benefits, identify those tests with good predictive value and help formulate practice recommendations. PMID- 17346338 TI - Matrix Metalloproteinase-9 (MMP-9) polymorphisms in patients with cutaneous malignant melanoma. AB - BACKGROUND: Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs) play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk. METHODS: We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis. RESULTS: We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site. CONCLUSION: This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression. PMID- 17346339 TI - Outcomes of decompression for lumbar spinal canal stenosis based upon preoperative radiographic severity. AB - BACKGROUND: The relationship between severity of preoperative radiographic findings and surgical outcomes following decompression for lumbar degenerative spinal canal stenosis is unclear. Our aim in this paper was to gain insight into this relationship. We determined pre-operative radiographic severity on MRI scans using strict methodological controls and correlated such severity with post operative outcomes using prospectively collected data. METHODS: Twenty-seven consecutive patients undergoing decompression for isolated degenerative spinal canal stenosis at L4-L5 were included. We measured cross-sectional area on MRI using the technique of Hamanishi. We categorized the severity of stenosis using Laurencin and Lipson's 'Stenosis Ratio'. We determined pre-operative status (prospectively) and post-operative outcomes using Weiner and Fraser's 'Neurogenic Claudication Outcome Score'. We determined patient satisfaction using standardized questionnaires. Each of these is a validated measure. Formal statistical evaluation was undertaken. RESULTS: No patients (0 of 14) with a greater than 50% reduction in cross-sectional area on pre-operative MRI had unsatisfactory outcomes. In contrast, outcomes for patients with less than or equal to 50% reduction in cross-sectional area had unsatifactory outcomes in 6 of 13 cases, with all but one negative outcome having a cross-sectional area reduction between 32% and 47%. CONCLUSION: The findings suggest that there appears to be a relationship between severity of stenosis and outcomes of decompressive surgery such that patients with a greater than 50% reduction in cross sectional area are more likely to have a successful outcome. PMID- 17346340 TI - The perceived meaning of a (w)holistic view among general practitioners and district nurses in Swedish primary care: a qualitative study. AB - BACKGROUND: The definition of primary care varies between countries. Swedish primary care has developed from a philosophic viewpoint based on quality, accessibility, continuity, co-operation and a holistic view. The meaning of holism in international literature differs between medicine and nursing. The question is, if the difference is due to different educational traditions. Due to the uncertainties in defining holism and a holistic view we wished to study, in depth, how holism is perceived by doctors and nurses in their clinical work. Thus, the aim was to explore the perceived meaning of a holistic view among general practitioners (GPs) and district nurses (DNs). METHODS: Seven focus group interviews with a purposive sample of 22 GPs and 20 nurses working in primary care in two Swedish county councils were conducted. The interviews were transcribed verbatim and analysed using qualitative content analysis. RESULTS: The analysis resulted in three categories, attitude, knowledge, and circumstances, with two, two and four subcategories respectively. A professional attitude involves recognising the whole person; not only fragments of a person with a disease. Factual knowledge is acquired through special training and long professional experience. Tacit knowledge is about feelings and social competence. Circumstances can either be barriers or facilitators. A holistic view is a strong motivator and as such it is a facilitator. The way primary care is organised can be either a barrier or a facilitator and could influence the use of a holistic approach. Defined geographical districts and care teams facilitate a holistic view with house calls being essential, particularly for nurses. In preventive work and palliative care, a holistic view was stated to be specifically important. Consultations and communication with the patient were seen as important tools. CONCLUSION: 'Holistic view' is multidimensional, well implemented and very much alive among both GPs and DNs. The word holistic should really be spelled 'wholistic' to avoid confusion with complementary and alternative medicine. It was obvious that our participants were able to verbalize the meaning of a 'wholistic' view through narratives about their clinical, every day work. The possibility to implement a 'wholistic' perspective in their work with patients offers a strong motivation for GPs and DNs. PMID- 17346341 TI - Choroidal melanoma metastasizing to maxillofacial bones. AB - BACKGROUND: Melanomas are malignant neoplasm of melanocytic origin, commonly seen on skin and various mucous membranes. Melanomas are the commonest intraocular malignant tumour in the adults. CASE PRESENTATION: A 50-year-old female presented with complains of painless progressive swelling in right cheek region of two months duration. Examination revealed a 6 x 4 cm bony hard swelling in right zygomatic region near and below lateral canthus of right eye with loss of vision. Investigations revealed it to be a choroidal melanoma metastasizing to the zygomatic bone. Patient was successfully treated by surgery. CONCLUSION: Choroidal melanoma, which commonly metastasizes to liver and lungs, never involves the lymph nodes and metastasis to facial bones is rare. Here we report a case of choroidal melanoma metastasizing to maxillofacial bones. PMID- 17346342 TI - GOTax: investigating biological processes and biochemical activities along the taxonomic tree. AB - We describe GOTax, a comparative genomics platform that integrates protein annotation with protein family classification and taxonomy. User-defined sets of proteins, protein families, annotation terms or taxonomic groups can be selected and compared, allowing for the analysis of distribution of biological processes and molecular activities over different taxonomic groups. In particular, a measure of functional similarity is available for comparing proteins and protein families, establishing functional relationships independent of evolution. PMID- 17346343 TI - Purulent pericarditis due to co-infection with Streptococcus pneumoniae and Mycobacterium tuberculosis in a patient with features of advanced HIV infection. AB - BACKGROUND: Both Mycobacterium tuberculosis and Streptococcus pneumoniae are common pathogens in patients with HIV infection. CASE PRESENTATION: We present an unusual case of purulent pericarditis resulting in cardiac tamponade due to infection with both organisms. We highlight the re-emergence of pneumococcal pericarditis in the HIV era and describe the pitfalls and challenges in the diagnosis of this condition. CONCLUSION: Clinicians working in HIV endemic areas need to consider dual infection with these organisms in patients who respond inadequately to either antibiotics or anti-tuberculous therapy alone. PMID- 17346344 TI - Single chain Fab (scFab) fragment. AB - BACKGROUND: The connection of the variable part of the heavy chain (VH) and and the variable part of the light chain (VL) by a peptide linker to form a consecutive polypeptide chain (single chain antibody, scFv) was a breakthrough for the functional production of antibody fragments in Escherichia coli. Being double the size of fragment variable (Fv) fragments and requiring assembly of two independent polypeptide chains, functional Fab fragments are usually produced with significantly lower yields in E. coli. An antibody design combining stability and assay compatibility of the fragment antigen binding (Fab) with high level bacterial expression of single chain Fv fragments would be desirable. The desired antibody fragment should be both suitable for expression as soluble antibody in E. coli and antibody phage display. RESULTS: Here, we demonstrate that the introduction of a polypeptide linker between the fragment difficult (Fd) and the light chain (LC), resulting in the formation of a single chain Fab fragment (scFab), can lead to improved production of functional molecules. We tested the impact of various linker designs and modifications of the constant regions on both phage display efficiency and the yield of soluble antibody fragments. A scFab variant without cysteins (scFabDeltaC) connecting the constant part 1 of the heavy chain (CH1) and the constant part of the light chain (CL) were best suited for phage display and production of soluble antibody fragments. Beside the expression system E. coli, the new antibody format was also expressed in Pichia pastoris. Monovalent and divalent fragments (DiFabodies) as well as multimers were characterised. CONCLUSION: A new antibody design offers the generation of bivalent Fab derivates for antibody phage display and production of soluble antibody fragments. This antibody format is of particular value for high throughput proteome binder generation projects, due to the avidity effect and the possible use of common standard sera for detection. PMID- 17346345 TI - Importance of c-Type cytochromes for U(VI) reduction by Geobacter sulfurreducens. AB - BACKGROUND: In order to study the mechanism of U(VI) reduction, the effect of deleting c-type cytochrome genes on the capacity of Geobacter sulfurreducens to reduce U(VI) with acetate serving as the electron donor was investigated. RESULTS: The ability of several c-type cytochrome deficient mutants to reduce U(VI) was lower than that of the wild type strain. Elimination of two confirmed outer membrane cytochromes and two putative outer membrane cytochromes significantly decreased (ca. 50-60%) the ability of G. sulfurreducens to reduce U(VI). Involvement in U(VI) reduction did not appear to be a general property of outer membrane cytochromes, as elimination of two other confirmed outer membrane cytochromes, OmcB and OmcC, had very little impact on U(VI) reduction. Among the periplasmic cytochromes, only MacA, proposed to transfer electrons from the inner membrane to the periplasm, appeared to play a significant role in U(VI) reduction. A subpopulation of both wild type and U(VI) reduction-impaired cells, 24-30%, accumulated amorphous uranium in the periplasm. Comparison of uranium accumulating cells demonstrated a similar amount of periplasmic uranium accumulation in U(VI) reduction-impaired and wild type G. sulfurreducens. Assessment of the ability of the various suspensions to reduce Fe(III) revealed no correlation between the impact of cytochrome deletion on U(VI) reduction and reduction of Fe(III) hydroxide and chelated Fe(III). CONCLUSION: This study indicates that c-type cytochromes are involved in U(VI) reduction by Geobacter sulfurreducens. The data provide new evidence for extracellular uranium reduction by G. sulfurreducens but do not rule out the possibility of periplasmic uranium reduction. Occurrence of U(VI) reduction at the cell surface is supported by the significant impact of elimination of outer membrane cytochromes on U(VI) reduction and the lack of correlation between periplasmic uranium accumulation and the capacity for uranium reduction. Periplasmic uranium accumulation may reflect the ability of uranium to penetrate the outer membrane rather than the occurrence of enzymatic U(VI) reduction. Elimination of cytochromes rarely had a similar impact on both Fe(III) and U(VI) reduction, suggesting that there are differences in the routes of electron transfer to U(VI) and Fe(III). Further studies are required to clarify the pathways leading to U(VI) reduction in G. sulfurreducens. PMID- 17346346 TI - Drug treatment program patients' hepatitis C virus (HCV) education needs and their use of available HCV education services. AB - BACKGROUND: In spite of the disproportionate prevalence of hepatitis C virus (HCV) infection among drug users, many remain uninformed or misinformed about the virus. Drug treatment programs are important sites of opportunity for providing HCV education to their patients, and many programs do, in fact, offer this education in a variety of formats. Little is known, however, about the level of HCV knowledge among drug treatment program patients, and the extent to which they utilize their programs' HCV education services. METHODS: Using data collected from patients (N = 280) in 14 U.S. drug treatment programs, we compared patients who reported that they never injected drugs (NIDUs) with past or current drug injectors (IDUs) concerning their knowledge about HCV, whether they used HCV education opportunities at their programs, and the facilitators and barriers to doing so. All of the programs were participating in a research project that was developing, implementing, and evaluating a staff training to provide HCV support to patients. RESULTS: Although IDUs scored higher on an HCV knowledge assessment than NIDUs, there were many gaps in HCV knowledge among both groups of patients. To address these knowledge gaps, all of the programs offered at least one form of HCV education: all offered 1:1 sessions with staff, 12 of the programs offered HCV education in a group format, and 11 of the programs offered this education through pamphlets/books. Only 60% of all of the participating patients used any of their programs' HCV education services, but those who did avail themselves of these HCV education opportunities generally assessed them positively. In all, many patients were unaware that HCV education was offered at their programs through individual sessions with staff, group meetings, and books/pamphlets, (42%, 49%, and 46% of the patients, respectively), and 22% were unaware that any HCV education opportunities existed. CONCLUSION: Efforts especially need to focus on ensuring that all drug treatment program patients are made aware of and encouraged to use HCV education services at their programs. PMID- 17346347 TI - Multilocus perspectives on the monophyly and phylogeny of the order Charadriiformes (Aves). AB - BACKGROUND: The phylogeny of shorebirds (Aves: Charadriiformes) and their putative sister groups was reconstructed using approximately 5 kilobases of data from three nuclear loci and two mitochondrial genes, and compared to that based on two other nuclear loci. RESULTS: Charadriiformes represent a monophyletic group that consists of three monophyletic suborders Lari (i.e., Laridae [including Sternidae and Rynchopidae], Stercorariidae, Alcidae, Glareolidae, Dromadidae, and Turnicidae), Scolopaci (i.e., Scolopacidae [including Phalaropidae], Jacanidae, Rostratulidae, Thinocoridae, Pedionomidae), and Charadrii (i.e., Burhinidae, Chionididae, Charadriidae, Haematopodidae, Recurvirostridae, and presumably Ibidorhynchidae). The position of purported "gruiform" buttonquails within Charadriiformes is confirmed. Skimmers are most likely sister to terns alone, and plovers may be paraphyletic with respect to oystercatchers and stilts. The Egyptian Plover is not a member of the Glareolidae, but is instead relatively basal among Charadrii. None of the putative sisters of Charadriiformes were recovered as such. CONCLUSION: Hypotheses of non-monophyly and sister relationships of shorebirds are tested by multilocus analysis. The monophyly of and interfamilial relationships among shorebirds are confirmed and refined. Lineage-specific differences in evolutionary rates are more consistent across loci in shorebirds than other birds and may contribute to the congruence of locus-specific phylogenetic estimates in shorebirds. PMID- 17346348 TI - Identification of high-risk subgroups in very elderly intensive care unit patients. AB - INTRODUCTION: Current prognostic models for intensive care unit (ICU) patients have not been specifically developed or validated in the very elderly. The aim of this study was to develop a prognostic model for ICU patients 80 years old or older to predict in-hospital mortality by means of data obtained within 24 hours after ICU admission. Aside from having good overall performance, the model was designed to reliably and specifically identify subgroups at very high risk of dying. METHODS: A total of 6,867 consecutive patients 80 years old or older from 21 Dutch ICUs were studied. Data necessary to calculate the Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II (SAPS II), Mortality Probability Models II scores, and ICU and hospital survival were recorded. Data were randomly divided into a developmental (n = 4,587) and a validation (n = 2,289) set. By means of recursive partitioning analysis, a classification tree predicting in-hospital mortality was developed. This model was compared with the original SAPS II model and with the SAPS II model after recalibration for very elderly ICU patients in the Netherlands. RESULTS: Overall performance measured by the area under the receiver operating characteristic curve and by the Brier score was similar for the classification tree, the original SAPS II model, and the recalibrated SAPS II model. The tree identified most patients with very high risk of mortality (9.2% of patients versus 8.9% for the original SAPS II and 5.9% for the recalibrated SAPS II had a risk of more than 80%). With a cut-point at a risk of 80%, the positive predictive values were 0.88 for the tree, 0.83 for the original SAPS II, and 0.87 for the recalibrated SAPS II. CONCLUSION: Prognostic models with good overall performance may also reliably identify subgroups of very elderly ICU patients who have a very high risk of dying before hospital discharge. The classification tree has the advantage of identifying the separate factors contributing to bad outcome and of using few variables. Up to 9.5% of patients were found to have a risk to die of more than 85%. PMID- 17346349 TI - Statistical tests to compare motif count exceptionalities. AB - BACKGROUND: Finding over- or under-represented motifs in biological sequences is now a common task in genomics. Thanks to p-value calculation for motif counts, exceptional motifs are identified and represent candidate functional motifs. The present work addresses the related question of comparing the exceptionality of one motif in two different sequences. Just comparing the motif count p-values in each sequence is indeed not sufficient to decide if this motif is significantly more exceptional in one sequence compared to the other one. A statistical test is required. RESULTS: We develop and analyze two statistical tests, an exact binomial one and an asymptotic likelihood ratio test, to decide whether the exceptionality of a given motif is equivalent or significantly different in two sequences of interest. For that purpose, motif occurrences are modeled by Poisson processes, with a special care for overlapping motifs. Both tests can take the sequence compositions into account. As an illustration, we compare the octamer exceptionalities in the Escherichia coli K-12 backbone versus variable strain specific loops. CONCLUSION: The exact binomial test is particularly adapted for small counts. For large counts, we advise to use the likelihood ratio test which is asymptotic but strongly correlated with the exact binomial test and very simple to use. PMID- 17346350 TI - Case-control and family-based association studies of candidate genes in autistic disorder and its endophenotypes: TPH2 and GLO1. AB - BACKGROUND: The TPH2 gene encodes the enzyme responsible for serotonin (5-HT) synthesis in the Central Nervous System (CNS). Stereotypic and repetitive behaviors are influenced by 5-HT, and initial studies report an association of TPH2 alleles with childhood-onset obsessive-compulsive disorder (OCD) and with autism. GLO1 encodes glyoxalase I, the enzyme which detoxifies alpha-oxoaldehydes such as methylglyoxal in all living cells. The A111E GLO1 protein variant, encoded by SNP C419A, was identified in autopsied autistic brains and proposed to act as an autism susceptibility factor. Hyperserotoninemia, macrocephaly, and peptiduria represent some of the best-characterized endophenotypes in autism research. METHODS: Family-based and case-control association studies were performed on clinical samples drawn from 312 simplex and 29 multiplex families including 371 non-syndromic autistic patients and 156 unaffected siblings, as well as on 171 controls. TPH2 SNPs rs4570625 and rs4565946 were genotyped using the TaqMan assay; GLO1 SNP C419A was genotyped by PCR and allele-specific restriction digest. Family-based association analyses were performed by TDT and FBAT, case-control by chi2, endophenotypic analyses for 5-HT blood levels, cranial circumference and urinary peptide excretion rates by ANOVA and FBAT. RESULTS: TPH2 alleles and haplotypes are not significantly associated in our sample with autism (rs4570625: TDT P = 0.27, and FBAT P = 0.35; rs4565946: TDT P = 0.45, and FBAT P = 0.55; haplotype P = 0.84), with any endophenotype, or with the presence/absence of prominent repetitive and stereotyped behaviors (motor stereotypies: P = 0.81 and 0.84, verbal stereotypies: P = 0.38 and 0.73 for rs4570625 and rs4565946, respectively). Also GLO1 alleles display no association with autism (191 patients vs 171 controls, P = 0.36; TDT P = 0.79, and FBAT P = 0.37), but unaffected siblings seemingly carry a protective gene variant marked by the A419 allele (TDT P < 0.05; patients vs unaffected siblings TDT and FBAT P < 0.00001). CONCLUSION: TPH2 gene variants are unlikely to contribute to autism or to the presence/absence of prominent repetitive behaviors in our sample, although an influence on the intensity of these behaviors in autism cannot be excluded. GLO1 gene variants do not confer autism vulnerability in this sample, but allele A419 apparently carries a protective effect, spurring interest into functional correlates of the C419A SNP. PMID- 17346351 TI - Bob-1 is expressed in classic Hodgkin lymphoma. AB - BACKGROUND: Almost all researchers agree on the lack of Bob-1 expression in Hodgkin/Reed-Sternberg (H/RS) cells in classic Hodgkin lymphoma (CHL), and utilize this marker as a diagnostic tool in conjunction with other markers to differentiate between lymphocyte predominance Hodgkin lymphoma (LPHL) and CHL. AIM: To study the immunohistochemical (IHC) expression of Bob-1 in Egyptian CHL and to correlate this expression with Epstein-Barr virus (EBV) viral load. MATERIALS AND METHODS: Paraffin sections of randomly selected 18 CHL cases were included: 2 lymphocyte rich (LR), 4 mixed cellularity (MC), 10 nodular sclerosis (NS) and 2 lymphocyte depletion (LD). All cases were immunostained for Bob-1. EBV was evaluated by EBV early RNA transcripts in situ hybridization (EBER ISH) and immunostaining for EBV latent membrane protein-1 (LMP-1). RESULTS: Sixty seven percent of cases (12/18) were positive for EBV by ISH and/or immunostaining for LMP-1. Moderate to strong nuclear Bob-1 was observed in 94% of cases. The positivity ranged between 25-100%. Bob-1 immunoreactivity was strongly associated with EBV positivity (p < 0.001). CONCLUSION: This study proves nuclear IHC expression of Bob-1 on H/RS in CHL implying the difficulties in applying this marker to differentiate between LPHL and CHL. Does this difference between Western and Egyptian CHL reflect genetic and/or environmental factors, or simply no difference exists as most researchers are concentrated on the Western population and no comparative studies have been done. Studies from other countries might answer this question. PMID- 17346352 TI - Identification of plant promoter constituents by analysis of local distribution of short sequences. AB - BACKGROUND: Plant promoter architecture is important for understanding regulation and evolution of the promoters, but our current knowledge about plant promoter structure, especially with respect to the core promoter, is insufficient. Several promoter elements including TATA box, and several types of transcriptional regulatory elements have been found to show local distribution within promoters, and this feature has been successfully utilized for extraction of promoter constituents from human genome. RESULTS: LDSS (Local Distribution of Short Sequences) profiles of short sequences along the plant promoter have been analyzed in silico, and hundreds of hexamer and octamer sequences have been identified as having localized distributions within promoters of Arabidopsis thaliana and rice. Based on their localization patterns, the identified sequences could be classified into three groups, pyrimidine patch (Y Patch), TATA box, and REG (Regulatory Element Group). Sequences of the TATA box group are consistent with the ones reported in previous studies. The REG group includes more than 200 sequences, and half of them correspond to known cis-elements. The other REG subgroups, together with about a hundred uncategorized sequences, are suggested to be novel cis-regulatory elements. Comparison of LDSS-positive sequences between Arabidopsis and rice has revealed moderate conservation of elements and common promoter architecture. In addition, a dimer motif named the YR Rule (C/T A/G) has been identified at the transcription start site (-1/+1). This rule also fits both Arabidopsis and rice promoters. CONCLUSION: LDSS was successfully applied to plant genomes and hundreds of putative promoter elements have been extracted as LDSS-positive octamers. Identified promoter architecture of monocot and dicot are well conserved, but there are moderate variations in the utilized sequences. PMID- 17346353 TI - A traditional Japanese-style salt field is a niche for haloarchaeal strains that can survive in 0.5% salt solution. AB - BACKGROUND: Most of the haloarchaeal strains have been isolated from hypersaline environments such as solar evaporation ponds, salt lakes, or salt deposits, and they, with some exceptions, lyse or lose viability in very low-salt concentrations. There are no salty environments suitable for the growth of haloarchaea in Japan. Although Natrialba asiatica and Haloarcula japonica were isolated many years ago, the question, "Are haloarchaea really thriving in natural environments of Japan?" has remained unanswered. RESULTS: Ten strains were isolated from a traditional Japanese-style salt field at Nie, Noto Peninsula, Japan by plating out the soil samples directly on agar plates containing 30% (w/v) salts and 0.5% yeast extract. They were most closely related to strains of three genera, Haladaptatus, Halococcus, and Halogeometricum. Survival rates in 3% and 0.5% SW (Salt Water, solutions containing salts in approximately the same proportions as found in seawater) solutions at 37 degrees C differed considerably depending on the strains. Two strains belonging to Halogeometricum as well as the type strain Hgm. borinquense died and lysed immediately after suspension. Five strains that belonged to Halococcus and a strain that may be a member of Halogeometricum survived for 1-2 days in 0.5% SW solution. Two strains most closely related to Haladaptatus possessed extraordinary strong tolerance to low salt conditions. About 20 to 34% of the cells remained viable in 0.5% SW after 9 days incubation. CONCLUSION: In this study we have demonstrated that haloarchaea are really thriving in the soil of Japanese-style salt field. The haloarchaeal cells, particularly the fragile strains are suggested to survive in the micropores of smaller size silt fraction, one of the components of soil. The inside of the silt particles is filled with concentrated salt solution and kept intact even upon suspension in rainwater. Possible origins of the haloarchaea isolated in this study are discussed. PMID- 17346354 TI - Glutamine induces heat-shock protein and protects against Escherichia coli lipopolysaccharide-induced vascular hyporeactivity in rats. AB - INTRODUCTION: Vascular hyporeactivity is an important problem associated with sepsis. Although the mechanism involves inflammatory pathway activation, specific therapeutic approaches have not been defined. Glutamine (Gln) has been shown to provide some anti-inflammatory effects and improve outcomes in sepsis. Here, we tested the hypothesis that Gln could reduce Escherichia coli lipopolysaccharide (LPS)-induced vascular hyporeactivity and evaluated the role of heat-shock protein 70 (HSP70) induction in this process. METHODS: Twenty-four male Sprague Dawley rats were divided into control, LPS shock, and alanyl-Gln dipeptide+LPS shock (Ala-Gln+LPS) groups. Six hours after administration of LPS, phenylephrine (PE) (0.5 to approximately 2.5 microg/kg) was applied intravenously to all groups, and the percentage increase in mean arterial pressure (MAP) was detected in the respective groups. The concentration-response curve of PE was obtained in tension experiments, and the average values of PE maximum efficacy (Emax) and median effective dose (EC50) were calculated. The plasma concentrations of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were detected in all groups. The expressions of HSP70 from heart, liver, lung, and aorta were also assayed in all groups. RESULTS: The maximal percentage increase in MAP induced by PE was significantly reduced to 12.7% in the LPS shock group (P < 0.05) and was restored to 15.6% in the Ala-Gln+LPS group (P < 0.05), whereas the control group was 24.7%. The average values of PE Emax and EC50 were significantly impaired in the LPS shock group (P < 0.05) but partially restored in the Ala-Gln+LPS group (P < 0.05). The expressions of HSP70 from the heart, aorta, lung, and liver were much higher in the Ala-Gln+LPS group than those in the LPS shock group (P < 0.05). The plasma concentrations of TNF-alpha, IL-6, and MDA were much lower in the Ala-Gln+LPS group than those in the LPS shock group. CONCLUSION: Gln effectively improves vascular reactivity by inducing the expression of HSP70, reducing inflammatory cytokine release and peroxide biosynthesis in LPS shock rats. These results suggest that Gln has a potentially beneficial therapeutic effect for septic shock patients. PMID- 17346355 TI - Intensive care unit acquired infection has no impact on long-term survival or quality of life: a prospective cohort study. AB - INTRODUCTION: The aim of this study was to evaluate the impact of intensive care unit (ICU)-acquired infection on long-term survival and quality of life. METHODS: Long-term survival was prospectively evaluated among hospital survivors who had stayed in a mixed, university-level ICU for longer than 48 hours during a 14 month study period during 2002 to 2003. Health-related quality of life was assessed using the five-dimensional EuroQol (EQ-5D) questionnaire in January 2005. RESULTS: Of the 272 hospital survivors, 83 (30.5%) died after discharge during the follow-up period. The median follow-up time after hospital discharge was 22 months. Among patients without infection on admission, long-term mortality did not differ between patients who developed and those who did not develop an ICU-acquired infection (21.7% versus 26.9%; P = 0.41). Also, among patients with infection on admission, there was no difference in long-term mortality between patients who developed a superimposed (35.1%) and those who did not develop a superimposed (27.6%) ICU-acquired infection (P = 0.40). The EQ-5D response rate was 75 %. The patients who developed an ICU-acquired infection had significantly more problems with self-care (50%) than did those without an ICU-acquired infection (32%; P = 0.004), whereas multivariate analysis did not show ICU acquired infection to be a significant risk factor for diminished self-care (odds ratio = 1.71, 95% confidence interval = 0.65-4.54; P = 0.28). General health status did not differ between those with and those without an ICU-acquired infection, as measured using the EuroQol visual-analogue scale (mean +/- standard deviation EuroQol visual-analogue scale value: 60.2 +/- 21 in patients without ICU-acquired infection versus 60.6 +/- 22 in those with ICU-acquired infection). The current general level of health compared with status before ICU admission did not differ between the groups either. Only 36% of those employed resumed their previous jobs. CONCLUSION: ICU-acquired infection had no impact on long-term survival. The patients with ICU-acquired infection more frequently experienced problems with self-care than did those without ICU infection, but ICU-acquired infection was not a significant risk factor for diminished self-care in multivariate analysis. PMID- 17346356 TI - In rats, oral oleoyl-DHEA is rapidly hydrolysed and converted to DHEA-sulphate. AB - BACKGROUND: Dehydroepiandrosterone (DHEA) released by adrenal glands may be converted to androgens and estrogens mainly in the gonadal, adipose, mammary, hepatic and nervous tissue. DHEA is also a key neurosteroid and has antiglucocorticoid activity. DHEA has been used for the treatment of a number of diseases, including obesity; its pharmacological effects depend on large oral doses, which effect rapidly wanes in part because of its short half-life in plasma. Since steroid hormone esters circulate for longer periods, we have studied here whether the administration of DHEA oleoyl ester may extend its pharmacologic availability by keeping high circulating levels. RESULTS: Tritium labelled oleoyl-DHEA was given to Wistar male and female rats by gastric tube. The kinetics of appearance of the label in plasma was unrelated to sex; the pattern being largely coincident with the levels of DHEA-sulfate only in females, and after 2 h undistinguishable from the results obtained using labelled DHEA gavages; in the short term, practically no lipophilic DHEA label was found in plasma. After 24 h only a small fraction of the label remained in the rat organs, with a different sex-related distribution pattern coincident for oleoyl- and free DHEA gavages. The rapid conversion of oleoyl-DHEA into circulating DHEA-sulfate was investigated using stomach, liver and intestine homogenates; which hydrolysed oleoyl-DHEA optimally near pH 8. Duodenum and ileum contained the highest esterase activities. Pure hog pancreas cholesterol-esterase broke down oleoyl DHEA at rates similar to those of oleoyl-cholesterol. The intestinal and liver esterases were differently activated by taurocholate and showed different pH activity patterns than cholesterol esterase, suggesting that oleoyl-DHEA can be hydrolysed by a number of esterases in the lumen (e.g. cholesterol-esterase), in the intestinal wall and the liver. CONCLUSION: The esterase activities found may condition the pharmacological availability (and depot effect) of orally administered steroid hormone fatty acid esters such as oleoyl-DHEA. The oral administration of oleoyl-DHEA in order to extend DHEA plasma availability has not been proved effective, since the ester is rapidly hydrolysed, probably in the intestine itself, and mainly converted to DHEA-sulfate at least in females. PMID- 17346357 TI - Evaluation of the structural quality of modeled proteins by using globularity criteria. AB - BACKGROUND: The knowledge of the three-dimensional structure of globular proteins is fundamental for a detailed investigation of their functional properties. Experimental methods are too slow for structure investigation on a large scale, while computational prediction methods offer alternatives that are continuously being improved. The international Comparative Assessment of Structure Prediction (CASP), an "a posteriori" evaluation of the quality of theoretical models when the experimental structure becomes available, demonstrates that predictions can be successful as well as unsuccessful, and this suggests the necessity for evaluations able to discard "a priori" the wrong models. RESULTS: We analyzed different structural properties of globular proteins for experimentally solved proteins belonging to the four different structural classes: "mainly alpha", "mainly beta", "alpha/beta" and "alpha+beta". The properties were found to be linearly correlated to protein molecular weight, but with some differences among the four classes. These results were applied to develop an evaluation test of theoretical models based on the expected globular properties of proteins. To verify the success of our test, we applied it to several protein models submitted to the sixth edition of CASP. The best theoretical models, as judged by CASP assessors, were in agreement with the expected properties, while most of the low quality models had not passed our evaluations. CONCLUSION: This study supports the need for careful checks to avoid the diffusion of incorrect structural models. Our test allows the evaluation of models in the absence of experimental reference structures, thereby preventing the diffusion of incorrect structural models and the formulation of incorrect functional hypotheses. It can be used to check the globularity of predicted models, and to supplement other methods already used to evaluate their quality. PMID- 17346358 TI - The kinetics of exsheathment of infective nematode larvae is disturbed in the presence of a tannin-rich plant extract (sainfoin) both in vitro and in vivo. AB - The mode of action of bioactive plants on gastrointestinal nematodes remains obscure. Previous in vitro studies showed that exsheathment was significantly disturbed after contact with tannin-rich extracts. However, the role of important factors (extract concentration, parasite species) has not been assessed and no information is available on the occurrence in vivo. These questions represent the objectives of this study. The model incorporated the parasites Haemonchus contortus and Trichostrongylus colubriformis with sainfoin as the bioactive plant. A set of in vitro assays was performed, measuring the changes observed, after 3 h of contact with increasing concentrations of sainfoin, on the rate of artificial exsheathment. The results indicated that sainfoin extracts interfered with exsheathment in a dose-dependent manner and the process overall was similar for both nematodes. The restoration of control values observed after adding PEG to extracts confirms a major role for tannins. A second study was performed in vivo on rumen-cannulated sheep fed with different proportions of sainfoin in the diet to verify these in vitro results. The consumption of a higher proportion of sainfoin was indeed associated with significant delays in Haemonchus exsheathment. Overall, the results confirmed that interference with the early step of nematode infection might be one of the modes of action that contributes to the anthelmintic properties of tanniniferous plants. PMID- 17346360 TI - Prediction of epidemic cholera due to Vibrio cholerae O1 in children younger than 10 years using climate data in Bangladesh. AB - To determine if a prediction of epidemic cholera using climate data can be made, we performed autoregression analysis using the data recorded in Dhaka City, Bangladesh over a 20-year period (1983-2002) comparing the number of children aged <10 years who were infected with Vibrio cholerae O1 to the maximum and minimum temperatures and rainfall. We formulated a simple autoregression model that predicts the monthly number of patients using earlier climate variables. The monthly number of patients predicted by this model agreed well with the actual monthly number of patients where the Pearson's correlation coefficient was 0.95. Arbitrarily defined, 39.4% of the predicted numbers during the study period were within 0.8-1.2 times the observed numbers. This prediction model uses the climate data recorded 2-4 months before. Therefore, our approach may be a good basis for establishing a practical early warning system for epidemic cholera. PMID- 17346359 TI - The relationship of meteorological conditions to the epidemic activity of respiratory syncytial virus. AB - Our aim was to obtain knowledge of how meteorological conditions affect community epidemics of respiratory syncytial virus (RSV) infection. To this end we recorded year-round RSV activity in nine cities that differ markedly in geographic location and climate. We correlated local weather conditions with weekly or monthly RSV cases. We reviewed similar reports from other areas varying in climate. Weekly RSV activity was related to temperature in a bimodal fashion, with peaks of activity at temperatures above 24-30 degrees C and at 2-6 degrees C. RSV activity was also greatest at 45-65% relative humidity. RSV activity was inversely related to UVB radiance at three sites where this could be tested. At sites with persistently warm temperatures and high humidity, RSV activity was continuous throughout the year, peaking in summer and early autumn. In temperate climates, RSV activity was maximal during winter, correlating with lower temperatures. In areas where temperatures remained colder throughout the year, RSV activity again became nearly continuous. Community activity of RSV is substantial when both ambient temperatures and absolute humidity are very high, perhaps reflecting greater stability of RSV in aerosols. Transmission of RSV in cooler climates is inversely related to temperature possibly as a result of increased stability of the virus in secretions in the colder environment. UVB radiation may inactivate virus in the environment, or influence susceptibility to RSV by altering host resistance. PMID- 17346361 TI - Prevalence, spatial distribution and the effect of control measures on louping ill virus in the Forest of Bowland, Lancashire. AB - The complex pathogen-host-vector system of the tick-borne louping-ill virus causes economic losses to sheep and red grouse in upland United Kingdom. This paper examines the spatial distribution, incidence and effect of control measures on louping-ill virus in the Bowland Fells of Lancashire. Seroprevalence in sheep at the beginning of the study varied within the area and was affected significantly by the frequency of acaricide treatment. There was a clear decrease over 5 years in the effective force of infection on farms implementing a vaccination programme, irrespective of acaricide treatment regime, however, only one third of farms apparently eliminated infection. On farms where vaccination did not occur or where vaccination was carried out intermittently, the estimated force of infection was variable or possibly increased. Thus, as befits a complex host-pathogen system, reductions in prevalence were not as dramatic as predicted; we discuss the potential explanations for these observations. PMID- 17346362 TI - Relevance of outcome measures in different cultural groups--does one size fit all? AB - It is estimated that 24 million people currently have dementia and that two thirds of them live in developing countries. However, most of the assessment instruments for dementia have originated in developed countries. This paper explores the relevance of outcome measures in clinical trials of dementia drugs in different cultural groups, particularly in developing countries. The challenges of assessing treatment benefits in dementia in such groups include linguistic and cultural diversity, as well as high illiteracy rates, lack of human resources and the time constraints in assessment of patients. This paper also highlights methodological issues in cross-cultural research of cognitive assessment. Improvement in neuropsychiatric outcomes may be of particular importance to people in non-Western cultures. Functional outcomes and global outcomes are potentially useful outcome measures, but more studies are required in various countries. The use of biological markers such as neuroimaging and cerebrospinal fluid studies may not be practical in developing countries due to their costs and acceptability respectively. More work is also needed in the area of quality of life measures in various countries. PMID- 17346363 TI - Neuropsychiatric symptoms (behavioral and psychological symptoms of dementia) and the development of dementia treatments. AB - Neuropsychiatric symptoms (NPS) are central features of dementia and an important treatment target. They should be assessed in future studies of emerging dementia therapies, using appropriate measures matched to the purpose of each study. Several significant issues remain regarding (1) the classification of these symptoms into syndromes, and (2) the development of better clinical measures for their quantification. In particular, effort should be directed at assessing their evolution over shorter time periods, and at using more objective methods in their measurement, such as actigraphy. These issues can be solved with nosologic study and other advances that could be brought about quickly, if appropriate time and effort are allocated. Empirical characterization of clinically meaningful change in NPS--by examining their relationship with dementia care burden, disability, quality of life, caregiver distress, and resource utilization--would be an important advance. PMID- 17346364 TI - Measuring quality of life in dementia: purposes, goals, challenges and progress. PMID- 17346365 TI - White matter microstructural abnormalities in late-life depression. AB - OBJECTIVE: To evaluate the location and the degree of white matter damage in late life depression using diffusion tensor imaging (DTI). METHODS: Thirty-one patients with late-life depression and 15 healthy volunteers matched for age, gender and years of education received conventional MRI (magnetic resonance imaging) and MR-diffusion tensor scanning. The fractional anisotropy (FA) values of white matter were measured respectively in frontal and temporal regions and the corpus callosum. RESULTS: FA values were significantly decreased in the frontal (superior and middle frontal gyrus), and temporal (right parahippocampal gyrus) regions of elderly patients with depression compared with healthy controls. CONCLUSION: Microstructural changes in the frontal (superior and middle frontal gyrus) and temporal (right parahippocampal gyrus) areas are associated with late-life depression. PMID- 17346366 TI - What real outcomes matter to caregivers? AB - Two surveys of caregivers of people with dementia were conducted in the U.K. and Poland. Among 64 U.K. carers, cognition, early diagnosis and general practitioner support were of particular concern to those caring for people with early dementia, while former carers were more concerned with pain, comfort and palliative issues. There was very strong support for better workforce training. In Poland, restoration of health and more time off from caring were the most desired outcomes. PMID- 17346367 TI - Clinical and economic outcomes--friend or foe? AB - The growing interest in analyzing the cost-effectiveness of interventions presents a challenge to anyone involved in dementia research. Although not yet often expressed as a formal requirement, drug authorities and budget holders also wish to have information on cost effectiveness. Clinical outcomes must therefore be combined with outcomes suitable for cost effectiveness analysis. However, issues about cost effectiveness are seldom included in empirical clinical trials, but are more often analyzed using modeling approaches. Clinical researchers and economists need to bridge these areas of potential conflict when long-term cost effectiveness is being considered. Randomized clinical trials (RCTs), observational studies, register data and economic models all have their advantages and drawbacks, and in making statements about cost effectiveness it is necessary to make a comprehensive judgment based on several methodological approaches. RCTs with a duration of at least 12 months should include assess ments of resource utilization, and outcomes should offer a link to population based cohort studies to discuss generalizability (e.g. a cognitive measure avail able both in trials and cohort studies, such as the Mini-mental State Examination (MMSE), staging instruments, quality of life instruments) of the costs, while also serving as one source of modeling. Both dementia-specific and generic quality of life instruments are required. Models are necessary but must be transparent so that the assumptions on which the models are built can be critically analyzed. PMID- 17346370 TI - Menu planning for childcare centres: practices and needs. AB - PURPOSE: Childcare menu planners' relevant knowledge, attitudes, and practices were determined, as were the menu planning guidelines or tools needed and the nutritional adequacy and quality of menus in licensed full-day childcare centres in Nova Scotia. METHODS: An ethics committee-approved questionnaire was mailed to a stratified random sample of 101 licensed childcare centres across the province. Respondents were instructed to forward a copy of their current four-week menu for nutrient analysis and menu quality evaluation. RESULTS: Descriptive statistical data analysis from the returned questionnaires (n=35) indicated that fewer than 50% of the menu planners had relevant training and knowledge. Discrepancies exist between attitudes about good menu planning and practices. A positive finding was that most respondents used reliable resources for menu planning and expressed a desire for updated resources and ongoing training in child nutrition/ menu planning. A number of nutrient and menu quality deficiencies were identified from the menus submitted (n=28). A significant statistical correlation was found between menu planning training and higher menu quality scores. CONCLUSIONS: The results will be relevant to nutritionists in the development of effective resources and training for childcare centre menu planners. PMID- 17346371 TI - Nursing home food services linked with risk of malnutrition. AB - PURPOSE: Links between food service characteristics and residents' risk of malnutrition were examined. METHODS: Cognitively intact residents meeting inclusion criteria and living in one of 38 participating nursing homes were randomly sampled. The final sample consisted of 132 residents, who were screened for risk of malnutrition and completed a face-to-face interview questionnaire about dining experiences. Additional data came from participants' medical charts, and each institution's food service manager completed a written questionnaire. Frequencies and logistic regressions were used to describe the sample and to examine relationships between risk of malnutrition and food service characteristics. RESULTS: Overall, 37.4% of participants were at risk of malnutrition. Food service factors, including food packages, lids, and dishes that were difficult to manipulate (b=0.285, p=0.009), bulk food-delivery systems (b=1.329, p=0.036), overall food satisfaction (b=0.253, p=0.044), menu cycle length (b=-2.162, p=0.003), and porcelain dishes (b=-0.345, p=0.052), all were significantly associated with risk of malnutrition. CONCLUSIONS: Our findings clearly show a need for nursing homes to modify certain aspects of food service that may increase the risk of malnutrition among cognitively intact residents. PMID- 17346372 TI - Widespread micronutrient inadequacies among adults in prince edward island. AB - PURPOSE: The prevalence of micronutrient inadequacies was assessed among adult residents of Prince Edward Island (PEI) in the PEI Nutrition Survey. METHODS: A peer-reviewed protocol was used in this cross-sectional survey, in which 24-hour recalls were administered during in-home interviews. A stratified random sample of 1,995 adults aged 18 to 74 participated. Median nutrient intakes with and without supplements were calculated; intakes were adjusted for day-to-day variability. Chi-square testing was used to assess differences in prevalence of inadequacy by age and sex. RESULTS: Most of the sample (more than 90%) had folate intakes below the Estimated Average Requirement (EAR). Magnesium and vitamin C intakes were low in more than 50% of the sample. Iron intakes were adequate in all groups except women aged 19 to 50, 29% of whom had intakes below the EAR. Women were more likely than men to have inadequate intakes. Median calcium intakes fell below recommendations for all age and sex groups. Supplement use had little impact on dietary adequacy in this sample. CONCLUSIONS: This study underscores the need for public health interventions designed to reduce the very high prevalence of nutrient inadequacies in the PEI adult population. In addition, education is needed on the selection of appropriate vitamin and mineral supplements. PMID- 17346373 TI - Once upon a time.... Storytelling to enhance teaching and learning. AB - PURPOSE: The impact of storytelling in the classroom was examined, as was what motivates individuals to engage in storytelling. METHODS: A storytelling methodology was introduced in an undergraduate nutrition course as an opportunity to enhance the teaching and learning environment. A 28-item, multi-part, self administered survey was then distributed to the class (n=17). RESULTS: Survey responses (n=15, 88% response) indicate that educators' and students' storytelling can positively influence the learning environment. This occurs through the creation of a greater focus on personalized information, glimpses of real-life experience, a connection with a topic as participants recognize similarities in their own personal experience and knowledge, and connections between different topics and through the emphasis on key concepts. Stories initiate useful conversations about unexplored struggles within practice, such as the emotional dimension(s) of an issue or what it means to be professional. Students are motivated to participate in storytelling through an external focus on others (i.e., helping others to learn) and an internal focus on self (i.e., seeking a connection with others to promote social dialogue). Several challenges related to the use of storytelling in the classroom emerged. CONCLUSIONS: Storytelling develops ways of knowing and dialoguing about issues, which has the potential to influence how students will approach their professional practice. PMID- 17346374 TI - Performance issues of dietetic interns: a dietetic educator's perspective. AB - PURPOSE: Dietetic internships provide practical experience leading, in most cases, to the attainment of entry-level dietetic competence. Problematic intern performance issues were examined, as were how educators resolve these issues and the supports they require to manage them. METHODS: A survey was electronically distributed to all Dietitians of Canada internship/university course directors (n=57). The response rate was 40% (n=23). RESULTS: Annually, 61% of internships involve challenging performance issues related to intern knowledge, skills, attitude, and behaviour. These issues manifest themselves individually or in combination as an intern's inability to apply/demonstrate appropriate knowledge/skill, a view/approach to the profession that is not in keeping with the organizational view, an attitude that is in conflict with program values, a negative response to feedback, an inability to relate to others, work habits that are in conflict with program values, and personal attributes that detract from the ability to meet program expectations. Educators respond to these issues by modifying their communications, the learning environment, and the program. CONCLUSIONS: Educators' strategies could be enhanced through consultation with other educators, mentor training, and the development of formal procedures. PMID- 17346375 TI - [Food choice and place of eating for Quebec children]. AB - PURPOSE: The relationships are explored between food choices of school-aged children and eating in the bedroom, while watching television, or in front of the computer. METHODS: Data were collected using a self-administered questionnaire that 534 subjects completed in class. Participants were ten- to 12-year-old children from Quebec. RESULTS: Significant positive correlations were found between the act of eating in the bedroom and eating in front of the television or the computer (p<0.05). Significant positive correlations were also found between eating in the bedroom, or eating in front of the television or the computer, and the consumption of low-density food, foods high in sugar and fat, and foods low in fibre (p<0.05). Data also revealed more negative food habits for boys than for girls (p<0.05). CONCLUSIONS: Because of the prevalence of childhood obesity, these findings support the need to document children's food consumption patterns and gender differences. PMID- 17346376 TI - Effect of processing on galactose in selected fruits. AB - PURPOSE: The impact of consuming processed versus fresh fruits and vegetables on the galactose intake of galactosemic patients was compared. METHODS: The galactose content of processed fruits was determined when the following processing methods were used: freezing, drying, blanching, microwaving, canning, and a combination of blanching and freezing. Then three-day food intakes of five subjects with galactosemia were recorded. The records were used to estimate galactose intake, according to previously reported galactose levels for fresh fruits and vegetables and the potential reduction in galactose intake when only processed fruits and vegetables are consumed. RESULTS: The average galactose reduction was approximately 45% for all the fruits and all processing methods, excluding drying. Intakes varied from 17 to 108 mg/day when fresh values were used and 11 to 103 mg/day when only processed fruits and vegetables were consumed. This reduction was statistically significant for four out of five patients. CONCLUSIONS: When the reduction is compared with reported daily fluctuations in galactosemic patients' endogenous galactose production, the clinical significance of reduced free galactose consumption on long-term outcome is unclear. However, metabolic dietitians now have objective data that the processing methods described will lower the free galactose content of the fruits analyzed. PMID- 17346377 TI - An experiential perspective on persecutory paranoia: a grounded theory construction. AB - Recently there has been a large volume of research on persecutory paranoia. Evidence has emerged for the role of social factors in the development of paranoia. There have, however, been no studies that have collaborated with users to develop an experiential perspective on paranoia. This study used a social constructionist version of grounded theory to develop an experiential perspective on persecutory paranoia. Ten individuals who had experience of persecutory paranoia were interviewed. The interviews were transcribed and analysed using the grounded theory method. A core process of fear and vulnerability was constructed. Subcategories of confusion and uncertainty, and self under attack contributed to the core process. These processes led to an engaging of the safety systems. Subthemes of these categories were identified. Many of these factors interacted to create the complex and dynamic experience of paranoia. Participants were often responding to genuinely frightening experiences but were also attacking themselves. Paranoia evolved as a mechanism of keeping oneself safe in dangerous situations. The need to negotiate a shared meaning of paranoia with users is emphasized. Direction for future research was discussed. PMID- 17346378 TI - A controlled trial of personal construct psychotherapy for deliberate self-harm. AB - Evidence for the effectiveness of psychological therapies for people who self harm is limited. Personal construct theory provides a model of self-harm and a framework for therapeutic intervention, which was evaluated in the present study. Sixty-four adults presenting to Accident and Emergency departments following self harm were allocated to a personal construct psychotherapy or a 'normal clinical practice' condition. They completed various measures at assessment points pre- and post-therapy. Repetition of self-harm was assessed over a 3-year period. Participants in the intervention condition showed significantly greater reduction in suicidal ideation, hopelessness and depression post-treatment than the control group; and significantly more reconstruing at this point and 6-month follow-up. There was some evidence suggestive of a lower frequency of repetition of self harm in the intervention than in the control group. It is concluded that brief personal construct psychotherapy may be effective for people who self-harm and merits further exploration. PMID- 17346379 TI - Correlates of self-harm behaviour in acutely ill patients with schizophrenia. AB - OBJECTIVE: This study compared acutely ill patients with schizophrenia with a history of self-harm (N=17) to those without a history of self-harm (N=16) on measures of depression, hopelessness, suicidal ideation, and demographic and psychiatric variables. A subgroup of these patients who experience auditory hallucinations, with and without a history of self-harm, were selected and compared on measures of depression, hopelessness, suicidal ideation and beliefs about voices. DESIGN: Employing a cross-sectional design, in-patients of two local psychiatric hospital, who met DSM-IV-TR criteria for schizophrenia and who were in an acute phase of the illness, were selected. METHOD: Each patient was assessed using the Beck Depressions Inventory (BDI), Beck Hopelessness Scale (BHS) and the Beck Suicide Scale (BSS). Patients who experienced auditory verbal hallucinations completed the Beliefs About Voices Questionnaire Revised (BAVQ-R). Patients with a history of self-harm completed the Beck Suicide Intent Scale (BSI). RESULTS: Patients with a history of self-harm (N=17) had significantly greater symptoms of depression, greater suicidal thoughts, increased number of hospital admissions, greater duration of illness and were more likely to be married, compared to patients without a history of self-harm (N=16). Among the subgroup of patients who experience auditory hallucinations, those with a history of self-harm (N=9), believed their voice to be more malevolent, had a tendency to resist their voice and experienced significantly greater symptoms of depression and hopelessness compared to those without a history of self-harm (N=6). CONCLUSIONS: These findings highlight the importance for screening by clinicians during inpatient hospital stays and for monitoring to be ongoing following discharge. For the subgroup of patients who experience auditory hallucinations, future research should seek to explore the relationship between self-harm and beliefs about voices. PMID- 17346380 TI - Course of improvement over 2 years in psychoanalytic and psychodynamic outpatient psychotherapy. AB - OBJECTIVE: To assess and predict the level and course of symptomatic improvement in psychoanalytic (PAP) and psychodynamic psychotherapy (PD). METHODS: In a comprehensive longitudinal study, the course of improvement of 116 patients in PAP and of 357 patients in PD was tracked over a period of 2 years and analysed via hierarchical linear models. RESULTS: At baseline, over 90% of the patients reported substantial psychological, physical or interpersonal distress. In both forms of treatment, the course of improvement could be adequately fitted by a linear model. Symptom distress decreased notably within 2 years, with an especially sharp decline before the first formally scheduled therapy session. No significant differences between forms of treatment as to level or pace of symptom improvement could be observed. Prediction of speed of improvement was poor, with initial symptom distress showing the strongest influence while initial helping alliance had no predictive value. When comparing patients who finished their treatment within the 2-year observation period with those with still ongoing treatments, the former showed quicker symptom improvement. DISCUSSION: Strategies for the optimal allocation of valuable therapeutic resources should be reconsidered. An adaptive, outcome-oriented allocation strategy of therapeutic resources is proposed. PMID- 17346381 TI - Criterion validity of the French version of Patient Health Questionnaire (PHQ) in a hospital department of internal medicine. AB - OBJECTIVES: Depressive disorders are overrepresented among the patients admitted to non-psychiatric units in general hospitals. However, the majority of depressed patients fail to be identified within this care setting. Since a self administered questionnaire (Patient Health Questionnaire, PHQ-9) has given encouraging results in English and Spanish, new research should test its criterion validity in a French-speaking environment. DESIGN: The study included 292 patients admitted to the internal medicine units of the University Hospitals of Geneva. Each patient filled the PHQ-9; 212 patients also underwent a blinded DSM-IV diagnostic assessment by a psychiatrist. METHODS: In order to assess the validity of PHQ-9 against the gold standard of the psychiatrist's DSM-IV diagnosis, we calculated overall accuracy, sensitivity, specificity, positive predictive value and Cohen kappa coefficients. We also studied the relationship between the PHQ-9 diagnostic and the severity of depression. Finally, analysis focused on the presence of a diagnosis of depression. RESULTS: Within the framework of the study, PHQ-9 showed an acceptable level of specificity. However, its sensitivity in detecting major depression was low (about 50% of false negative results). As regards the overall presence of depressive disorders, this instrument performed hardly any better (35% of false negatives). Other characteristics of the population under investigation may have affected the data. CONCLUSIONS: The French version of PHQ-9 demonstrated low sensitivity as compared with psychiatrist-established diagnosis of DSM-IV A criterion and major depressive episode. PMID- 17346382 TI - Young people's experiences of individual psychoanalytic psychotherapy. AB - Greater emphasis is currently being placed on user involvement in shaping the delivery of mental health services and the need for increasing the evidence base for psychotherapeutic interventions such as individual psychoanalytic psychotherapy (IPP). This qualitative study reports on the range of experiences of six young people aged between 16 and 21 years in undertaking IPP. Interpretative phenomenological analysis was used to develop an in-depth understanding of their experiences. The themes identified the young people's initial expectations and concerns about starting psychotherapy, experiences of learning the ropes of therapy and the process and meaning of ending therapy. The affective relationship with the therapist was of particular importance to the young people concerned. Positive experiences of IPP included being listened to and being accepted, and talking and thinking in depth. The power differentials with respect to being a patient were also evident. The paper concludes by suggesting that paying greater attention to young people's views of psychotherapy may improve their initial engagement and help to develop services in more appropriate ways. Qualitative methodologies provide a useful adjunct to conducting process and outcome research in this context. PMID- 17346383 TI - Befriending patients with medication-resistant schizophrenia: can psychotic symptoms predict treatment response? AB - OBJECTIVES: Supportive interventions are used in schizophrenia, but little research has been conducted into whether any baseline variable predicts treatment response. The aim of this study was to establish if baseline delusions or hallucinations are associated with changes in overall symptoms in patients who received a befriending intervention. DESIGN: The sample consisted of 44 patients with schizophrenia. These patients comprised the befriending arm of a multicentre randomized controlled trial which compared the efficacy of using CBT against befriending as an adjunct to routine care for patients with medication-resistant schizophrenia. METHODS: Scores for auditory hallucinations and delusions relating to persecution or control were entered into two regression models. The dependent variables were change in overall symptoms (1) between baseline and end of the intervention, and (2) between baseline and 9 months post-intervention. RESULTS: Baseline delusions predicted a good response and auditory hallucinations predicted a poor response at 9 months. CONCLUSIONS: Baseline psychotic symptoms strongly predicted outcome in this sample. The finding that hallucinations predicted a poor outcome is consistent with previous research. These results may help to determine which patients would benefit from supportive interventions. PMID- 17346384 TI - A qualitative investigation of problem gambling as an escape-based coping strategy. AB - BACKGROUND: There has been a small but growing body, of largely quantitative research, that has examined problem gambling in the context of poor coping skills. These studies suggest that gambling may be used as an alternative method of coping that some will use to distract themselves from having to deal with problems in their lives. OBJECTIVES: To examine the role that gambling plays in the lives of problem gamblers and the extent to which it may be used as a means of coping. DESIGN: Fifty problem gamblers, ranging in age from 18 to 63 years, with an average age of 39 years, were interviewed. The focus of the interview was upon the participant's accounts of how their gambling problem had developed and the role that gambling played in their lives. A structured grounded theory approach was utilized. RESULTS: Following the selective coding process, 'gambling to escape' was identified as the core category. This state was achieved through 'mood modification', involving fantasies, dissociation and/or changes in arousal. For some problem gamblers seeking mood modification was their primary motivation. For others mood modification was sought as a means to cope with one or two other psychological and/or psychosocial states consisting of 'filling the void' and/or 'avoiding problems'. Two other factors sometimes influenced the need to gamble, either directly through 'control beliefs' or through 'cognitive regret'. CONCLUSIONS: Escape was the prime characteristic of the gambling experience that facilitated the continuation of problem gambling among the interviewed participants. In relation to these findings, the implications for prevention, intervention, treatment and future research are discussed. PMID- 17346385 TI - More than just a place to talk: young people's experiences of group psychological therapy as an early intervention for auditory hallucinations. AB - OBJECTIVES: Auditory hallucinations are extremely distressing, particularly when occurring during adolescence. They may be most responsive to psychological intervention during a three-year critical period following symptom-onset, but as yet no studies have investigated voices groups for young participants with adolescent-onset psychosis. The aim of the current study is to explore the experience of group-CBT amongst a group of young people experiencing distressing auditory hallucinations. DESIGN: This project was planned and conducted in the tradition of idiographic, qualitative psychology. A small purposive sample was selected, and in-depth, open-ended interviews were conducted, in order to generate and explore rich, experiential accounts which are clearly situated and contextualized. METHODS: Eight participants who had completed a cognitive behavioural group intervention were interviewed using a semi-structured interview schedule. The transcribed data were analysed according to the principles of Interpretative Phenomenological Analysis (IPA; Smith, Osborn, & Jarman, 1999). RESULTS: Two superordinate themes emerged. The first describes experiential features of the respondents' accounts of group therapy. The second theme posits a cyclical relationship between four key factors: the content of the hallucinated voices, the participants' explanations for, and reactions to these voices, and thus, their ability to cope with them. CONCLUSIONS: 'Voices groups' are appreciated by young people with auditory hallucinations, as sources of therapy, information, and support. These results suggest a number of testable hypotheses about the efficacy of group treatment and its future development. PMID- 17346386 TI - Getting clients to hear: applying principles and techniques of Kiesler's Interpersonal Communication Therapy to assessment feedback. AB - Limited attention has been paid to the process of providing assessment feedback and few concrete recommendations exist for the practicing clinician. The author proposes that principles and techniques of Kiesler's (1979, 1982, 1988, 1996) Interpersonal Communication Therapy (ICT) can be applied to guide the provision of assessment feedback. Using such an approach has the potential to increase the likelihood that information is heard, accepted, integrated, and acted upon. A review of current research on the provision of assessment results is supplied along with a description of basic ICT principles and techniques. Practical suggestions for applying elements of ICT in this context are given along with a discussion of the rationale for integrating such a model into the assessment process. PMID- 17346387 TI - When what I wish makes me worse ... to make coherence flexible. AB - This paper describes a psychotherapeutic constructivist intervention oriented to the resolution of implicative dilemmas, in order to promote personal change. It presents a clinical case study of a client with depression and with some dependent and obsessive functioning. The Repertory Grid Technique was administered along with symptom assessment (SCL-90-R) both at beginning and end of the psychotherapeutic process. Exploring themes emerged from Repgrid, several narratives, experiential and metaphoric strategies were used in order to explore and reconstruct meanings associated with the five implicative dilemmas found. The therapeutic process succeeds at solving dilemmas as found in the post-therapy assessment. This resolution was accompanied by symptom reduction. In conclusion, the utility of implicative dilemmas as a marker to understand the therapeutic impasse and dysfunctional system coherence is discussed, as well as the efficacy of the strategies used in this clinical case concerning its adaptation to working with implicative dilemmas that prevent therapeutic process. PMID- 17346388 TI - Delayed diagnosis of infarcted small bowel due to right-sided Bochdalek hernia. AB - We report a case of an adult patient with small bowel infarction, secondary to a strangulated Bochdalek hernia. PMID- 17346389 TI - Aortic injury using the Hasson trocar: a case report and review of the literature. AB - Case reports of major vascular injury during open primary access during laparoscopy are very limited. An injury to the aorta with the Hasson trocar is documented here, followed by a review of the literature on major vascular injury during primary access. PMID- 17346390 TI - Non-classical presentation of congenital cholesteatoma. AB - Congenital cholesteatoma is a rare entity. It arises from aberrant epithelial remnants left at the time of closure of the neural groove, between the 3rd and 5th week of embryonic life. Otoscopy typically shows a pearly white mass, medial to the intact tympanic membrane, primarily in the anterosuperior quadrant, without a preceding history of otorrhoea, tympanic membrane perforation or surgery. It can present at any age from birth to early adulthood. The most common presenting symptom is hearing loss or facial nerve palsy. We present a non classical presentation of congenital cholesteatoma with loss of taste sensation and numbness on the anterior two-thirds of the tongue associated with a bulging posterosuperior quadrant of the ipsilateral tympanic membrane in a 52-year-old male. After investigation, the patient underwent surgical management resulting in improvement of his symptoms. PMID- 17346391 TI - Prolonged postoperative altered mental status after methylene blue infusion during parathyroidectomy: a case report and review of the literature. AB - Methylene blue (5 mg/kg) is routinely given at our institution during parathyroidectomy. The dye stains the parathyroid glands and helps in better surgical visualisation. The technique is generally considered to be safe except for causing pseudo-cyanosis. We report a case of a patient who had confusion, agitation and altered mental status during the early postoperative course probably secondary to methylene blue infusion. PMID- 17346392 TI - Allergy to technetium-labelled nanocolloidal albumin for sentinel node identification. AB - Optimal sentinel node identification requires using the combination technique with blue dye and radiocolloid. Allergic reactions to the common blue dyes in use are well recognised. In this report, we present a patient with breast carcinoma who developed a type I hypersensitivity reaction to intradermal injection of technetium-99m labelled nanocolloidal albumin. While reactions to colloids are rare, and in this case minor, operators using this radiopharmaceutical should be prepared for a potential severe anaphylactic reaction. PMID- 17346393 TI - An unusual hernia complication: a late presentation. AB - A 67-year-old man presented with a 10-year history of intermittent right iliac fossa pain. His only significant past medical history was an inguinal hernia repair 10 years ago. After investigations, the patient underwent a laparotomy. He had a localised caecal perforation secondary to a misplaced prolene suture. A right hemicolectomy was performed. PMID- 17346394 TI - Laparoscopic cholecystectomy in situs inversus totalis with left-sided gall bladder. AB - Symptomatic gallstones in patients with situs inversus pose diagnostic and therapeutic challenges. The presentation and management of one such patient is discussed with an emphasis on operative technique. PMID- 17346395 TI - Postoperative arrhythmias in general surgical patients. AB - INTRODUCTION: New-onset arrhythmias are a common problem in cardiothoracic surgery. They are also common following major non-cardiac surgery. This review examines the available literature to establish the incidence and significance of new-onset arrhythmias following major non-cardiothoracic surgery. MATERIALS AND METHODS: A literature search was performed using the Medline and Pubmed databases using the terms 'post-operative arrhythmia', 'peri-operative arrhythmia', 'atrial fibrillation/flutter', 'supraventricular arrhythmia/tachycardia', 'cardiac complications' and 'non-cardiothoracic surgery'. Articles were cross-referenced for additional relevant publications and reviewed for data regarding new-onset arrhythmias following major non-cardiothoracic surgery. RESULTS: There was considerable heterogeneity in the literature regarding cardiac monitoring, types of arrhythmias considered and potential associations investigated, thus hindering interpretation. The available data suggest that new-onset arrhythmias affect about 7% of patients following major non-cardiothoracic surgery. These arrhythmias are often associated with other underlying complications. PMID- 17346396 TI - The treatment of varicose veins. AB - INTRODUCTION: Over the past few years, there has been a move to less invasive endoluminal methods in the treatment of lower limb varicose veins combined with a renewed interest in sclerotherapy, with the recent addition of foam sclerotherapy. The development of these new techniques has led many to question some of the more conventional teaching on the treatment of varicose veins. This review examines these new treatments for lower limb varicose veins and the current evidence for their use. MATERIALS AND METHODS: An extensive search of available electronic and paper-based databases was performed to identify studies relevant to the treatment of varicose veins with particular emphasis on those published within the last 10 years. These were analysed by both reviewers independently. RESULTS: There is no single method of treatment appropriate for all cases. Conventional surgery is safe and effective and is still widely practised. Whilst the new treatments may be popular with both surgeons and patients, it is important that they are carefully evaluated not only for their clinical benefits and complications when compared to existing treatments but also for their cost prior to their wider acceptance into clinical practice. PMID- 17346399 TI - Anatomy in a modern medical curriculum. AB - Anatomy in undergraduate education has been in decline for many years. Some suggest that it has fallen below a safe level. Balances between detail and safety, and assimilation and application of anatomy have yet to be established as the methods of teaching undergo another metamorphosis. For doctors, the human body is the focus of investigation and intervention on a daily basis; for this reason, the study of anatomy in some form will continue to be essential to safe medical practice. It is necessary for core knowledge of anatomy to be assimilated by all doctors in order to practice and communicate safely. It may be true that most doctors do not need to dissect a cadaver or study a prosection in order to practice, but if it can improve their understanding of what they do and why they do it, this surely has to be of benefit both for the safety of the patient and satisfaction of the doctor as a professional. Integration of newer teaching modalities and modern technology will encourage interest and retention of anatomical knowledge and its clinical relevance. Anatomy has a promising future in postgraduate specialist and surgical training. Detailed knowledge should be integrated into specialist training when it is clinically relevant allowing specialists of the future to practice safely and accurately and also to provide a strong base for future clinical developments. PMID- 17346401 TI - Reducing referral-to-treatment waiting times in cancer patients using a multidisciplinary database. AB - INTRODUCTION: Modern delivery of cancer care through patient-centred multidisciplinary teams (MDT) has improved survival. This approach, however, requires effective on-going co-ordination between multiple specialties and resources and can present formidable organisational challenges. The aim of this study was to improve the efficiency of the MDT process for head and neck cancer. PATIENTS AND METHODS: A systems analysis of the MDT process was undertaken to identify bottlenecks delaying treatment planning. The MDT process was then audited. A revised process was developed and an Intranet-based data management solution was designed and implemented. The MDT process was re-evaluated to complete the audit cycle. RESULTS: We designed and implemented a trust-wide menu driven database with interfaces for registering and tracking patients, and automated worklists for pathology and radiology. We audited our MDT for 11 and 10 weeks before and following the introduction of the database, with 226 and 187 patients being discussed during each period. The database significantly improved cross-specialtity co-ordination, leading to a highly significant reduction in the number of patients whose treatment planning was delayed due to unavailability of adjunctive investigations (P < 0.001). This improved the overall efficiency of the MDT by 60%. CONCLUSIONS: The NHS Cancer Plan aspires to reduce the referral to-treatment time to 1 month. We have shown that a simple, trust-wide database reduces treatment planning delays in a sizeable proportion of head and neck cancer patients with minimal resource implications. This approach could easily be applied in other MDT meetings. PMID- 17346400 TI - Open versus laparoscopic radical prostatectomy. The case for open radical prostatectomy. PMID- 17346402 TI - A review of current practices in breast conservation surgery in the UK. AB - INTRODUCTION: The aim of this study was to assess whether surgeons in the UK were practising wide excision consistent with current guidelines and current evidence. PATIENTS AND METHODS: Questionnaires were sent to 200 breast surgeons throughout the UK to determine current practices in breast conserving surgery. RESULTS: When performing a wide excision for invasive cancer, 61% of respondents always remove full thickness of breast tissue and 37% usually do. Of surgeons, 60% rarely use specimen X-ray for palpable lesions. However, 91% always take specimen X-rays in impalpable lesions, but 9% do not always take specimen X-rays for impalpable lesions. In 93% of units, the pathologist always reports the distance to the nearest margin. For both invasive and in situ cancer, there is a wide variation in what is considered an adequate radial margin. There is wide variation in the practice of re-excision. Of surgeons, 50% indicated that they wish wider margins in the presence of an extensive in situ component and 39% wish wider margins in younger women. CONCLUSIONS: The results show a large variation in practice with many surgeons not treating patients in accordance with current guidelines and evidence. PMID- 17346403 TI - Nipple discharge: a sign of breast cancer? AB - INTRODUCTION: Nipple discharge is regarded a sign of breast cancer. Type of discharge and cytology are unreliable for diagnosis. Most malignant cases have a detectable breast mass. The aim of this study was to assess the association between nipple discharge and breast cancer. PATIENTS AND METHODS: Patients who underwent operation for nipple discharge at a district general hospital (population 460,000) over a 3-year period were included. All had normal clinical, radiological and cytological examination. Operation and histopathology reports were reviewed. RESULTS: Eighty-six patients underwent operation for nipple discharge. Median age was 54 years (range, 32-84 years). Analysis of nipple discharge revealed red blood cells (RBCs) in 35 patients (40%). At operation, 81 patients underwent radical sub-areola duct excision (Hadfield's procedure) and five microdochectomy. Histopathology reported duct ectasia in 59 patients and benign ductal papilloma in 25. Two patients had occult malignancy - DCIS (1) and LCIS (1). No invasive cancer was found. CONCLUSIONS: Nipple discharge alone is not usually a sign of breast cancer. Occult malignancy is rare. A period of 'watchful waiting' may prevent patients undergoing unnecessary surgery. PMID- 17346404 TI - Cancer genetics clinics and the surgeon: a valuable role for family history screening. AB - INTRODUCTION: This study examines how a colorectal surgeon can use a regional cancer genetics service to deal safely and efficiently, with community referrals for colorectal cancer screening on the basis of family history. PATIENTS AND METHODS: A retrospective review of consecutive asymptomatic people with a strong family of colorectal cancer referred by the surgeon to the genetics service over a 30-month period. RESULTS: A total of 45 people were referred by the surgeon to the cancer genetics service. Following official verification of family histories, 15 were thought to be in a low-risk category for developing colorectal cancer, 18 were moderate risk, 4 had a high-to-moderate risk and 2 satisfied the criteria for HNPCC. After official authentication, it was discovered that 20% of people had mistakenly informed the surgeon of important inaccuracies in their family history. CONCLUSIONS: The cancer genetics service seeks to identify accurately those at increased risk of developing colorectal cancer due to their family history. It has the time, resources and expertise to verify officially a family history that cannot be properly done in a busy surgical clinic. This study shows that it can provide a valuable role for correctly identifying and counselling people who truly require screening due to their familial predisposition for colorectal cancer. PMID- 17346405 TI - Pancreas-sparing distal duodenectomy for infrapapillary neoplasms. AB - INTRODUCTION: For neoplasms that arise in the third and fourth parts of the duodenum (D(3), D(4)), a duodenectomy that preserves the pancreas can provide adequate tumour clearance while avoiding the additional dissection and risk of the common alternative, pancreatoduodenectomy. PATIENTS AND METHODS: Pancreas sparing distal duodenectomy (PSDD) was performed in 14 patients with infrapapillary duodenal neoplasms between 1991-2002, and the clinical outcome is reviewed. The operation entails careful separation of the lower pancreatic head from D(3), complete mobilisation of the ligament of Treitz and end-to-end duodenojejunal anastomosis 1-3 cm below the major duodenal papilla. RESULTS: There were 9 men and 5 women of median age 56 years, who presented with iron deficiency anaemia (n = 8), gastric outlet obstruction (n = 4), anaemia and gastric outlet obstruction (n = 1), epigastric pain or mass (1 each). There were 11 malignant neoplasms (adenocarcinoma 5, stromal tumour 4, recurrent seminoma 1, plasmacytoma 1), 2 benign neoplasms (villous adenoma, lipoma) and 1 patient with steroid-induced ulceration. In addition to D(3) and D(4), resection included the distal part of D(2) in 5 patients, while 4 required concomitant partial colectomy. Median operation time was 240 min and median blood loss 1197 ml, being greater for malignant than benign lesions (1500 ml versus 700 ml). There was one death from gangrenous cholecystitis, one early re-operation for anastomotic bleeding and one late re-operation for delayed gastric emptying secondary to anastomotic stricture, but no pancreatic complications. At a median follow-up of 47 months, three patients had died of recurrent disease while the other 10 were alive and well with no upper gastrointestinal symptoms. CONCLUSIONS: Provided there is a minimum 1-cm clearance at the papilla, PSDD is a useful alternative to formal pancreatoduodenectomy in patients with unusual neoplasms arising from the third and fourth parts of the duodenum. Although a major undertaking in its own right, it avoids the extra time of a pancreatic resection and the extra risk of a pancreatic anastomosis. PMID- 17346406 TI - Decreasing the blood transfusion rate in elective hip replacement surgery using an autologous drainage system. AB - INTRODUCTION: This is a prospective study looking at the effectiveness of autologous postoperative drains in primary uncemented total hip replacement (THR) surgery. PATIENTS AND METHODS: A total of 86 patients were studied, with 43 using standard suction drains (normal drain group) and 43 using autologous drains (autologous drain group). RESULTS: Thirty-seven units of homologous blood were transfused in the normal drain group and 5 units in the autologous drain group. The mean number of units of homologous blood transfused per patient was reduced from 0.86 to 0.12 (P < 0.01) with the use of autologous drains and the transfusion rate was reduced from 23% to 6% (P < 0.02). The mean length of hospital stay was also reduced by two nights (P < 0.05). There were no adverse effects from using the autologous system and it does reduce the need for a homologous blood transfusion. CONCLUSIONS: The system is simple and easy to use and we have also found it to be cost effective. Previously, it has not been reported as being effective in hip arthroplasty surgery, unlike knee arthroplasty surgery. We would recommend using autologous postoperative drains in primary THR surgery. PMID- 17346407 TI - Wound oozing after total hip arthroplasty. AB - INTRODUCTION: Total hip arthroplasty is a commonly performed operation and yet little information exists about the duration of wound oozing, the factors associated with this and the implications. The aim of this work was to identify factors influencing wound oozing by establishing their effect on the time taken for wounds to cease oozing after total hip arthroplasty. PATIENTS AND METHODS: Sixty-two consecutive patients undergoing total hip arthroplasty were included. Wounds were examined for wound oozing on a daily basis by the same observer and were then re-dressed. The time taken for each wound to become dry was recorded. Data were analysed to determine if the time-to-dryness was influenced by wound length, body mass index, estimated volume of blood in the dissected tissues, duration of surgery and ASA grade. RESULTS: Time to dryness was associated with wound length (P = 0.01), body mass index (BMI, P = 0.05), estimated volume of blood in dissected tissues (P = 0.05) and length of hospital stay (P = 0.02). No association was found with duration of surgery or ASA grade. CONCLUSIONS: A small incision, meticulous haemostasis at surgery and a reduction in pre-operative obesity reduce the time taken for hip arthroplasty wounds to become dry. Prolonged wound oozing delays hospital discharge. PMID- 17346408 TI - Learning curves in orthopaedic surgery: a case for super-specialisation? AB - INTRODUCTION: The objective of this study was to assess if there is a significant learning curve in the treatment of developmental dysplasia of the hip. PATIENTS AND METHODS: We followed up cases of developmental dysplasia of the hip treated by a single surgeon over a 12-year period. There were 96 cases, 56 treated by open reduction and 40 treated by closed reduction. Assessment was made of the incidence and degree of avascular necrosis in the treated hips, as a radiological outcome measure. RESULTS: Plotting the cumulative percentage of satisfactory outcomes demonstrated an increasingly high percentage of satisfactory results with increasing number of procedures performed, i.e. as the surgeon progressed up the 'learning curve'. CONCLUSIONS: This study demonstrates a learning curve in the treatment of developmental dysplasia of the hip. It may be possible to draw parallels to other treatments, and also support for the growing trend to specialisation. PMID- 17346409 TI - The detection of patients with 'fragility fractures' in fracture clinic - an audit of practice with reference to recent British Orthopaedic Association guidelines. AB - INTRODUCTION: The British Orthopaedic Association published guidelines on the care of fragility fracture patients in 2003. A section of these guidelines relates to the secondary prevention of osteoporotic fractures. The objective of this audit was to compare practice in our fracture clinic to these guidelines, and take steps to improve our practice if required. PATIENTS AND METHODS: We retrospectively audited the treatment of all 462 new patients seen in January and February 2004. Using case note analysis, 38 patients who had sustained probable fragility fractures were selected. Six months' post-injury, a telephone questionnaire was administered to confirm the nature of the injury and to find out whether the patient had been assessed, investigated or treated for osteoporosis. A second similar audit was conducted a year later after steps had been taken to improve awareness amongst the orthopaedic staff and prompt referral. RESULTS: During the first audit period, only 5 of 38 patients who should have been assessed and investigated for osteoporosis were either referred or offered referral. This improved to 23 out of 43 patients during the second audit period. CONCLUSIONS: Improvements in referral and assessment rates of patients at risk of further fragility fractures can be achieved relatively easily by taking steps to increase awareness amongst orthopaedic surgeons, although additional strategies and perhaps the use of automated referral systems may be required to achieve referral rates nearer 100%. PMID- 17346410 TI - Cement burn of the skin during hip replacement. AB - We present the first reported case of a partial thickness burn to the skin from discarded bone cement during a routine total hip replacement (THR). The patient required plastic surgical attention for 5 months before the skin was healed. We summarise the reported incidents of cement burns to various other structures and the circumstances in which these injuries can potentially occur. PMID- 17346411 TI - The role of percutaneous endopyelotomy for ureteropelvic junction obstruction. AB - INTRODUCTION: Over the last 20 years, the surgical management of ureteropelvic junction obstruction (UPJO) has been revolutionised by the development of endourological instrumentation and several minimally invasive procedures including: antegrade or retrograde endopyelotomy, retrograde balloon dilatation, and laparoscopic pyeloplasty. Currently, in our department, we offer percutaneous antegrade endopyelotomy (PAE) as primary treatment of UPJO in adults, believing it offers less morbidity, better cosmetic results, and quicker operating time compared with open pyeloplasty. PATIENTS AND METHODS: We performed a retrospective audit of our results for the 14 patients who underwent percutaneous antegrade endopyelotomy between January 2000 and May 2004. RESULTS: Mean operative time was 53 min (range, 30-80 min), mean in-patient stay was 3.8 days (range, 2-7 days), and there were no major postoperative complications for this series with mean follow-up of 31.8 months (range, 12-52 months). Eleven out of the 14 patients (79%) showed radiological improvement on their 3-month MAG 3 (mercaptoacetyl-triglycyl) renogram, and 13 out of the 14 (93%) patients reported significant reduction or resolution of pain, compared with their preoperative state. CONCLUSIONS: The majority of urologists still offer open pyeloplasty as primary treatment for UPJO with laparoscopic pyeloplasty currently an evolving procedure in the UK. Our series reports comparable success rates for PAE compared to other series. Despite these results, we feel that the future role of percutaneous endopyelotomy will be as a salvage procedure following failed open or laparoscopic surgery. However, in patients with concurrent stone disease or requiring antegrade ureteric access, percutaneous endopyelotomy would be suitable as a primary treatment option. PMID- 17346412 TI - A 15-year longitudinal analysis of trends in elective urological surgery - an evidence base for Modernising Medical Careers. AB - INTRODUCTION: The impact of Modernising Medical Careers on the differential need for consultant urologists and urological surgeons is as yet unknown. This study's aim was to determine what changes there had been in operative urological activity so as to predict the need for urological surgeons in the future. MATERIALS AND METHODS: A retrospective study of all elective operative urological surgery over a 15-year period was performed. The absolute numbers of patients presenting for different grades of surgery were aggregated and analysed using the Spearman's rank correlation test. RESULTS: Aggregated data from 27,839 procedures demonstrated no change in the number of operations (r 0.01; NS) or the number of diagnostic endoscopic procedures (r 0.21; NS) carried out over the study period. There was a decrease in endoscopic surgery related to a 70% reduction in trans urethral resection of the prostate (TURP) (r -0.89; P = <0.0001) and an increase in ureteroscopic interventions (r 0.82; P = 0.0002) for stone disease. There was no change in the amount of major surgery carried out (r -0.43; NS) over the 15 years. CONCLUSIONS: There have been changes to the pattern of surgery urologists have provided over the last 15 years but the need for complex surgical interventions has not altered. This suggests there will be as great a need for operating surgeons in the future, as currently exists. PMID- 17346413 TI - Current attitudes and practices towards diathermy smoke. AB - INTRODUCTION: The hazards of surgical smoke are well documented and electrosurgical units (ESUs) are an integral part of surgical practice. The aim of this study was to gauge the opinions of general surgical consultants, specialist registrars and senior theatre nurses in the Wessex Region towards the hazards of ESU smoke. MATERIALS AND METHODS: A literature search was carried out using Ovid Medline. A questionnaire was sent to 169 consultants, SpRs and nurses in the 14 hospitals across the Wessex Region, exploring current practices, perceived hazards and whether adequate precautions were currently in use. RESULTS: Only 3 of 98 surgeons used dedicated smoke extractors, despite the fact the majority (72%) felt that, currently, inadequate precautions were taken to protect staff and patients from surgical smoke. There was also uncertainty about the hazards amongst the respondents. CONCLUSIONS: The use of smoke extraction equipment is very limited. Greater awareness of the hazards and available technology to extract fumes from the theatre environment might lead to greater uptake. PMID- 17346414 TI - Diagnostic fine-needle aspiration in postoperative wound infections is more accurate at predicting causative organisms than wound swabs. AB - INTRODUCTION: Postoperative wound infections are common. Antibiotics are often prescribed empirically, usually in the absence of any microbiological sensitivity data. This study demonstrates the role of fine-needle aspiration microbiology (FNAM) in determining the causative organisms in these wounds compared to wound swabs taken from the same patients. PATIENTS AND METHODS: A total of 20 patients with clinical signs of soft tissue infection were tested using wound swabs and fine-needle aspiration. RESULTS: Six of the wound swabs yielded a single organism but 16 out 20 of the FNAM group yielded a single organism (P = 0.002). CONCLUSIONS: The FNAM approach allows antibiotic sensitivities to be obtained enabling specific antimicrobial therapy to be implemented early. FNAM also has a higher yield of cultures than wound swabs. Cellulitic areas can be sampled even when use of wound swabs is not possible. PMID- 17346415 TI - Perfidious gallbladders - a diagnostic dilemma with xanthogranulomatous cholecystitis. AB - INTRODUCTION: Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis characterised by marked thickening of the gallbladder wall and dense local adhesions. Pre-operative and intra-operative diagnosis is difficult and it often mimics a gallbladder carcinoma (GBC). Laparoscopic cholecystectomy (LC) is frequently unsuccessful with a high conversion rate. A series of patients with this condition led us to review our experience with XGC and to try to develop a care pathway for its management. PATIENTS AND METHODS: A retrospective review of the medical records of 1296 consecutive patients who had undergone cholecystectomy between January 2000 and April 2005 at our hospital was performed. Twenty-nine cases of XGC were identified among these cholecystectomies. The clinical, radiological and operative details of these patients have been analysed. RESULTS: The incidence of XGC was 2.2% in our study. The mean age at presentation was 60.3 years with a female:male ratio of 1.4:1. Twenty-three patients (79%) required an emergency surgical admission at first presentation. In three patients, a GBC was suspected both radiologically and at operation (10.3%), but was later disproved on histology. Seventeen patients (59%) had obstructive jaundice at first presentation and required an endoscopic retrograde cholangiopancreatography (ERCP) before LC. Of these, five had common bile duct stones. Abdominal ultrasound scan showed marked thickening of the gallbladder wall in 16 cases (55%). LC was attempted in 24 patients, but required conversion to an open procedure in 11 patients (46% conversion rate). A total cholecystectomy was possible in 18 patients and a partial cholecystectomy was the choice in 11 (38%). The average operative time was 96 min. Three patients developed a postoperative bile leak, one of whom required ERCP and placement of a biliary stent. The average length of stay in the hospital was 6.3 days. CONCLUSIONS: Severe xanthogranulomatous cholecystitis often mimics a gallbladder carcinoma. Currently, a correct pre-operative diagnosis is rarely made. With increased awareness and a high index of suspicion, radiological diagnosis is possible. Preoperative counselling of these patients should include possible intra-operative difficulties and the differential diagnosis of gallbladder cancer. Laparoscopic cholecystectomy is frequently unsuccessful and a partial cholecystectomy is often the procedure of choice. PMID- 17346419 TI - Quality of surgical instruments. PMID- 17346420 TI - Appropriate surgical hand antisepsis. PMID- 17346421 TI - Use of nomogram to predict acute urinary retention. PMID- 17346422 TI - BAFF and rheumatic autoimmune disorders: implications for disease management and therapy. AB - Interest in B-cells has been revived due to the description of new functions. Supporting a role for B-cells in the genesis of autoimmune diseases is the fact that the B-cell activating factor of the TNF ligand family (BAFF) is essential in their physiology. However, in each disease, this is restricted to a subgroup of patients. Based on experiments in mice, and validated in humans, this new cytokine has been highlighted. Excessive production of BAFF alters immune tolerance by rescuing self-binding B-cells. Overexpression in mice leads to autoimmune manifestation, and BAFF levels are elevated in the serum of autoimmune patients. Similar abnormalities occur in chronic lymphocytic leukemia. Recent works suggest that antagonizing the protein (or competing for its receptors) is relevant to the treatment. Advances in our understanding of the BAFF system offers the opportunity to improve our therapeutic approach. PMID- 17346423 TI - In vitro stem cell cultures from human dental pulp and periodontal ligament: new prospects in dentistry. AB - In spite of the vast knowledge of tooth development and of the various kinds of specialized bone/tooth-associated cells, the characteristics and properties of their precursor cell populations present in the postnatal organism are little known, as is their possible therapeutic use. Taken together dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) possess stem-cell-like qualities, including self-renewal capability and multi-lineage differentiation. Regenerative medicine is based on stem cells, signals and scaffolds. Transplantation of those cells, which can be obtained from an easily accessible tissue resource and expanded in vitro, holds promise as a therapeutic approach for reconstruction of tissues and bone in vivo. PMID- 17346424 TI - Increased expression of specific thioredoxin family proteins; a pilot immunohistochemical study on human hepatocellular carcinoma. AB - Hepatocellular Carcinoma (HCC) is one of the most frequent cancers worldwide, however, prognosis remains poor following its discovery. We investigate the Thioredoxin superfamily of proteins as diagnostic markers for HCC. Furthermore, we delineate possible roles of the endoplasmic reticulum member of the superfamily, ERdj5, in carcinogenesis. Using antibodies against Thioredoxin 1, Thioredoxin Reductase 1 and ERdj5, we performed immunohistochemistry on paraffin embedded liver biopsy sections from HCC patients. All three redox proteins exhibited elevated expression levels in tumor tissue compared to internal control, with ERdj5 showing a remarkable 3-fold increase. In vitro cell viability experiments using Hepatocellular Carcinoma HuH7 cells treated with ERdj5 small interfering RNA showed that ERdj5 knockdown cells exhibited less resistance to Doxorubicin (chemotherapy drug), but more resistance to Tunicamycin (Endoplasmic Stress inducer), compared to control cells. In conclusion, we introduce members of the Thioredoxin superfamily as possible immunohistochemical markers in the diagnostics of hepatocellular carcinoma and indicate a potential defensive role for ERdj5 in chemotherapeutic drug resistance. PMID- 17346425 TI - Reparixin, a specific interleukin-8 inhibitor, has no effects on inflammation during endotoxemia. AB - Reparixin antagonizes interleukin-8 (IL-8) on the level of signal transduction in vitro. We hypothesized that IL-8 mediates some of the reactions occurring during acute inflammation and specifically that IL-8 may be a mediator of endotoxin induced neutrophilia. We therefore tested the effects of reparixin on humoral and cellular parameters in LPS-induced acute systemic inflammation. The study is a randomized (3:2 active:placebo), double-blind, placebo-controlled parallel group trial. Twenty healthy male volunteers randomly received either reparixin (12) or placebo (8) intravenously. One hour after the start of reparixin/placebo infusion a bolus of 2 ng/kg endotoxin was infused over 1-2 min. Blood samples were obtained over 24 h. Reparixin, being metabolized to ibuprofen, suppressed serum thromboxane B2 levels by 78 percent compared to baseline and control at 8 h. LPS induced neutrophilia was not significantly affected by reparixin in human volunteers. Consistently, reparixin did not alter the lymphocyte or monocyte counts and had no effect on LPS-induced systemic inflammation as measured by tumor necrosis factor alpha (TNF-alpha) or interleukin-6 (IL-6) release. Regulation of IL-8 receptors CXCR1 and 2 and the degranulation marker CD11b showed the expected kinetics. Reparixin had no effect on thrombin formation as measured by prothrombin fragment (F1+2). In conclusion, our study showed that reparixin was safe but had no impact on endotoxin induced inflammation. In contrast to previous studies with its metabolite ibuprofen, reparixin does not enhance inflammation in this model. PMID- 17346426 TI - Interleukin-6, interleukin-10 and heat shock protein-90 expression in renal epithelial neoplasias and surrounding normal-appearing renal parenchyma. AB - Cytokines, notably the interleukins IL-6 and IL-10, have an important role in the development and progression of renal-cell carcinomas, acting in the host-tumor interaction and in tumor bulk. Heat shock proteins (HSP), in particular HSP-90, may have a regulatory role in cytokine biosynthesis and prognostic implication in some tumors. To define the roles of the cytokines IL-6 and IL-10 and HSP-90 in the progression of renal-cell carcinoma we analyzed immunohistochemical expression of these proteins in human renal-cell carcinomas from 95 total nephrectomies. IL-6, IL-10 and HSP-90 proteins were more strongly expressed in epithelium and stroma of the renal tumoral compartment than in adjacent normal peritumoral tissue. But the difference reached significance only for HSP-90 protein. The percentage of cells expressing IL-6, IL-10 and HSP-90 immunoreactivity was higher in benign epithelial tumors, than in normal peritumoral tissue, but lower than in renal-cell carcinomas. Whereas HSP-90 immunoreactivity seemed higher in more aggressive histological phenotypes (collecting-duct carcinoma) of renal-cell carcinomas, IL-10 protein levels were higher in more advanced TNM stage (pT3) tumors. Our observation suggests that IL 6 and IL-10 and HSP-90 may be useful markers associated with the development and progression of renal-cell carcinomas and have independent functional roles in this malignant condition. PMID- 17346427 TI - Induction of macrophage glutamine: fructose-6-phosphate amidotransferase expression by hypoxia and by picolinic acid. AB - We studied the expression of glutamine: fructose-6-phosphate amidotransferase (GFAT), the rate limiting enzyme in the hexosamine biosynthetic pathway controlling protein glycosylation. We obtained the first evidence that the GFAT mRNA and protein are constitutively expressed in murine mononuclear phagocytes (Mf) and inducible by picolinic acid (PA), a catabolite of tryptophan, hypoxia and desferrioxamine (DFX). These stimuli share the property to transactivate gene expression through the Hypoxia Responsive Element (HRE). The promoter of GFAT contains the consensus sequence of HRE in position 74/-65 (GFAT-HRE), and we studied the role of HRE on the activation of the promoter utilizing appropriate expression vectors. We found that GFAT-HRE is essential for the response to hypoxia, PA or DFX and that Hypoxia Inducible Factor-1alpha (HIF-1alpha) can augment this response. Finally, we demonstrate that iron chelation is part of the mechanism by which PA and DFX activate GFAT expression. Our results provide the first indication that hypoxia, PA or DFX induce the transcription of GFAT gene in murine Mf cell lines and that the HRE of the promoter is essential for this response. PMID- 17346428 TI - Nuclear factor kappaB activity is increased in peripheral blood mononuclear cells of children affected by atopic and non-atopic eczema. AB - Atopic and non-atopic eczema is an inflammatory cutaneous disease which is common in childhood and is associated with a dysregulation of the immune system. Many genes encoding immune receptors, cytokines, chemokines, chemokine receptors, and adhesion molecules involved in the development of the disease are under the control of transcription factors belonging to the nuclear factor (NF)-kappaB family. To investigate the role of NF-kappaB in the development of eczema, 20 children, affected by relapsing chronic eczema, were enrolled in this study. Eleven of the 20 children showed IgE immunoreactivity and had a positive prick test. The DNA binding activity of NF-kappaB in nuclear extracts of the patients' peripheral blood mononuclear cells (PBMC) was examined by electrophoretic mobility shift assay. We found that basal NF-kappaB-DNA binding activity in PBMC was significantly higher in the eczema patient group in comparison with the same parameter in the healthy age-matched control group. Moreover, we observed a significant correlation between NF-kappaB-DNA binding activity and patients clinical score (SCORAD). Based on these observations we speculate that NF-kappaB can play an important role in the immunopathogenesis of eczema and therefore could be considered as a potential therapeutic target. PMID- 17346429 TI - Mast cell deficient W/Wv mice have lower serum IL-6 and less cardiac tissue necrosis than their normal littermates following myocardial ischemia-reperfusion. AB - Myocardial ischemia-reperfusion (IR) injury complicates all forms of coronary artery revascularization. Circulating interleukin-6 (IL-6) has been implicated in cell death following a variety of stimuli. Macrophages, platelets, neutrophils and the endothelium have been shown to release IL-6 after IR injury. Cardiac mast cells have been implicated in IR; however, their involvement has never been quantified. In this randomized, prospective study, we compared cardiac tissue susceptibility and serum IL-6 changes between mast cell deficient (W/Wv) mice and their normal littermates (+/+). Twenty-eight male W/Wv mice (n=14) and their +/+ littermates (n=14) were anaesthetized with 2.5% isoflurane. The left coronary artery (LCA) was ligated for 30 minutes or a sham procedure was performed. After 6 hours of reperfusion, the animals were sacrificed. The muscle viability was assessed on fresh whole-mount slices by nitroblue tetrazolium (NBT) histochemical assay and serum IL-6 concentrations measured by ELISA. Cardiac muscle viability was significantly higher in W/Wv mice than the +/+ mice. Serum IL-6 levels were higher in the +/+ sham mice (465 +/- 32 pg/ml, n=6) than the W/Wv mice (185 +/- 31 pg/ml, n=6), p < 0.001. The IL-6 levels increased significantly after reperfusion only in the +/+ mice (698 +/- 41 pg/ml, n=8, p = 0.001), while it remained similar in the W/Wv mice (202 +/- 48 pg/ml, n=8, p = 0.783). These results show that the absence of mast cells reduces the myocardial damage associated with IR injury. Furthermore, there is an attenuation in the inflammatory response, as measured by serum IL-6 levels, following this local insult. This finding entertains the prospect of developing prophylactic therapy- targeting selective inhibition of cardiac mast cell activation, in clinical situations involving medical or surgical myocardial revascularization. PMID- 17346430 TI - HLA-A2.1-restricted T cells react to SEREX-defined tumor antigen CML66L and are suppressed by CD4+CD25+ regulatory T cells. AB - The question of whether T cell responses to SEREX-defined tumor antigens are under regulation of naturally occurring CD4+CD25+ regulatory T cells (nTreg cells) has not been answered. To address this issue, we first identified an HLA A2.1-restricted T cell antigen epitope of SEREX-identified tumor antigen CML66L, 66Pa. The HLA-A2.1/66Pa peptide complex in vitro stimulated the in vivo-primed T cells as shown by increased T cell proliferation, higher secretion of the T cell cytokine interferon-gamma (IFN-gamma), increased production of intracellular IFN gamma in CD8+ T cells, and higher T cell-mediated cytotoxicities of CML66L+ human tumor cells. This suggests that CML66L elicits T cell immune responses. We also developed a novel internal reference epitope for identification of T cell epitopes by construction of chimeric CML66L containing myeloid antigen proteinase 3 epitope Pr1 as a control. Finally, we found that nTreg cells regulates T cell responses to 66Pa, and that depletion of nTreg cells via a pro-apoptotic protein Bax-dependent mechanism enhances polyclonal T cell responses to 66Pa. These findings provide new insights into the T cell participation in SEREX-defined anti tumor immune responses and novel direction in enhancement of anti-leukemia immunotherapy by modulation of homeostasis of nTreg cells. PMID- 17346431 TI - Prolonged remission of neuro-Behcet disease following autologous transplantation. AB - Two young male patients with severe progressive Behcet's disease with neurological involvement (N-BD) were treated by high-dose immunosuppressive chemotherapy (HIC) followed by autologous CD34+ selected peripheral blood stem cell transplantation (APBSCT). Neurological impairment and disability were quantified by means of Expanded Disability Status Scale (EDSS). Neuroimaging included spine and brain MRI and brain SPECT by radiolabeling technetium (Tc99m) Ethyl Cisteynate Dimer (ECD). Disease progression halted after treatment in both patients. At 48 months of follow-up they were therapy-free and one showed neurological status and disability improvement. Brain MRI findings were unchanged in both patients, but SPECT-ECD showed an increase of blood flow in the hypoperfused cerebral areas in the ameliorated patient. Immune ablation followed by APBSCT can modify the course of severe N-BD. Because of the high risk and the transplant-related mortality, these cases have to be carefully selected. PMID- 17346432 TI - Antibiotic treatment alone for acute rhinosinusitis gives a poor response in allergic children. AB - Acute rhinosinusitis (ARS) is frequent in children. Patients with allergic rhinitis show signs of more impaired paranasal sinus functioning than normal subjects during viral colds. This study evaluated the effectiveness of administering antibiotics alone to treat ARS in both allergic and non-allergic children. We obtained informed consent from the parents of each patient enrolled in the study. 97 children, 55 males and 42 females aged between 4 and 9 years (46 of whom were allergic), suffering from ARS, were treated with amoxicilline clavulanate (50 mg/Kg bid) for 14 days. Symptoms and endoscopic signs of illness were evaluated at baseline and immediately after treatment. Symptoms improved significantly (p<0.001) after treatment in 84 patients, equally distributed between allergic and non-allergic subjects. On the contrary, endoscopic signs disappeared only in 49 children, 9 of whom were allergic (OR 14.9, 95%CI 4.6 40.1, p<0.001). Slight to fair agreement was observed between clinical symptoms and endoscopic signs (agreement 64% , Kappa=0.28, McNemar test p<0.001). Antibiotic therapy alone in the treatment of ARS may be generally insufficient to resolve symptoms, mainly endoscopic signs. Moreover, in allergic children this issue appears to be more evident. PMID- 17346433 TI - Genetic predisposition to rheumatoid arthritis in a Tuscan (Italy) ancient human remain. AB - Rheumatoid arthritis (RA) is currently believed to have originated in America, and after the discovery of this continent in 1492, to have been exported to the Old World. We evaluated the genetic predisposition to RA in the "Braids Lady" from Arezzo (Italy), a partially mummified woman's body dating back to the end of 1500 AD which presents the anatomical and pathological features of this disease. The study of the polymorphic HLA-DRB1 locus, which includes alleles strongly associated with RA onset, has received much attention over recent years, especially the loci codifying for the DR1 and DR4 antigens, widely represented in the Mediterranean population, and for DR14, widespread among Native Americans. Molecular analysis was performed on extracts of DNA from the mummy, firstly from histological bone sections and then from the whole bone. Two different HLA typing techniques, PCR-sequence-specific oligonucleotides (PCR-SSO) and PCR-sequence specific primers (PCR-SSP), were employed to identify HLA-DRB alleles. Both genotyping methods showed that the "Braids Lady" carried the DRB1*0101 allele, the serological equivalent of the DR1 antigen. Although the possession of RA risk factor genes cannot be considered a diagnostic marker, the positive result of the Italian mummy for DRB1*0101 and the RA features present, support the idea that this pathology was present in the Old World from at least the mid-16th century. A pathogenetic hypothesis of RA which might well explain its worldwide diffusion is the "molecular mimicry", resulting from a cross-reactive antibody response between certain microbial antigens and shared epitopes of specific HLA-DR1, DR4 and DR14 susceptibility alleles, the frequency of which varies among different ethnic groups. PMID- 17346434 TI - Longer resistance of some DNA traits from BT176 maize to gastric juice from gastrointestinal affected patients. AB - The presence of antibiotic resistance marker genes in genetically engineered plants is one of the most controversial issues related to Genetically Modified Organism (GMO)-containing food, raising concern about the possibility that these markers could increase the pool of antibiotic resistance genes. This study investigates the in vitro survival of genes bla and cryIA(b) of maize Bt176 in human gastric juice samples. Five samples of gastric juice were collected from patients affected by gastro-esophageal reflux or celiac disease and three additional samples were obtained by pH modification with NaHCO3. DNA was extracted from maize Bt176 and incubated with samples of gastric juices at different times. The survival of the target traits (bla gene, whole 1914 bp gene cry1A(b), and its 211 bp fragment) was determined using PCR. The stability of the target genes was an inverse function of their lengths in all the samples. Survival in samples from untreated subjects was below the normal physiological time of gastric digestion. On the contrary, survival time in samples from patients under anti-acid drug treatment or in samples whose pH was modified, resulted strongly increased. Our data indicate the possibility that in particular cases the survival time could be so delayed that, as a consequence, some traits of DNA could reach the intestine. In general, this aspect must be considered for vulnerable consumers (people suffering from gastrointestinal diseases related to altered digestive functionality, physiological problems or drug side-effects) in the risk analysis usually referred to healthy subjects. PMID- 17346435 TI - Immunoglobulin-A profile in breast milk from mothers delivering full term and preterm infants. AB - Recent advances in the care of low-birth-weight and preterm neonates have stimulated research into the best dietetic program to improve their survival and short/long term outcome. Some components of human milk that cannot be included in artificial formulas may be critical for survival. Of these, immunoglobulins are important, and in particular secretory immunoglobulins A (sIgA). The concentration of secretory IgA was measured by immunoblotting (an immunoelectrophoretic technique having high specificity and reliability) in milk from mothers delivering at term (TM) or prematurely (PM). In both groups, IgA concentrations were high very early on but quickly decreased during the first week of lactation. The early IgA mean concentration was higher in PM than in TM but, because of high variability in PM milk, the difference rarely reached statistical significance. This variability during lactation reflects the important role of human milk in supplying immunological factors to cope with the gastrointestinal absorption of high molecular weight proteins in the first days of life. Immunological protection is particularly critical for a preterm baby, so it is important to promote feeding with its own mothers milk if possible, paying strict attention to the timing of milk collection. PMID- 17346436 TI - Improvement of clinical response in allergic rhinitis patients treated with an oral immunostimulating bacterial lysate: in vivo immunological effects. AB - Allergic rhinitis is known to be one of the most common chronic diseases in the industrialized world. According to the concept that allergic rhinitis patients generally suffer from an immune deficit, in order to stimulate specifically or aspecifically their immune system, immunomodulating agents from various sources, such as synthetic compounds, tissue extracts or a mixture of bacterial extracts, have been used. The aim of the present trial is to evaluate the efficacy of the treatment with an immunostimulating vaccine consisting of a polyvalent mechanical bacterial lysate (PMBL) in the prophylaxis of allergic rhinitis and subsequently to analyze its in vivo effects on immune responses. 41 allergic rhinitis patients were enrolled: 26 patients were randomly assigned to the group for PMBL sublingual treatment and 15 others to the group for placebo treatment. For all 26 patients blood samples were drawn just before (T0) and after 3 months of PMBL treatment (T3) to evaluate plasma IgE levels (total and allergen-specific) and the cytokine production involved in the allergic response (IL-4, IFN-gamma). The results of our study indicate that PMBL is effective in vivo in the reduction or in the elimination of the symptoms in rhinitis subjects during the treatment period in comparison to a non-immunostimulating treatment. A significant and clinically relevant improvement was found in 61.5%, a stationary clinical response was registered in 38.4% and no negative side effects associated with the medication or worsening were recorded. At the end of a 3-month follow up period the clinical picture remained the same as that observed at T3. PMBL treatment did not affect the serum IgE levels (either total or allergen-specific) and did not induce significant changes in IFN-gamma concentration. In contrast, PMBL therapy may be accompanied, in some patients, by a potential immunomodulating activity by decreasing IL-4 cytokine expression. PMID- 17346437 TI - Penile cutaneous temperature in systemic sclerosis: a thermal imaging study. AB - Systemic Sclerosis is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart and kidney. Moreover men with systemic sclerosis (SSc) present an increased risk of developing erectile dysfunction (ED). Recently, we evaluated the extent of penile vascular damage in sclerodermic patients using Duplex ultrasonography. The aim of this paper is to investigate whether penile thermal differences exist between sclerodermic patients and healthy controls. For this reason 10 men with SSc receiving current treatment for their disease, and 10 healthy controls were enrolled; penile thermal properties were assessed through non-contact thermal imaging (functional Infra Red Imaging fIRI); erectile function was evaluated using the sexual health inventory for men (SHIM) questionnaire. The SHIM results confirmed the presence of ED in sclerodermic patients. Baseline penile temperature in patients (32.1 +/- 1.4 degrees C) was lower than in controls (34.1 +/- 0.9 degrees C). Recovery from cooling test was seen to be faster in healthy controls than in patients, both in terms of recovery amplitude (patients 3.75 +/- 2.09 degrees C, controls 9.80 +/- 2.77 degrees C) and amplitude to time constant ratio (patients 1.21 +/- 0.64 degrees C/min, controls 1.96 +/- 0.48 degrees C/min). These results show that penile thermal abnormalities occur in almost all sclerodermic patients. Non-contact thermal imaging not only identifies thermal alterations but also clearly distinguishes between SSc patients and healthy controls and therefore could represent a valuable instrument in identifying early ED in SSc patients. PMID- 17346438 TI - Inflammation and atherosclerosis: the role of TNF and TNF receptors polymorphisms in coronary artery disease. AB - Inflammation plays an important role in the pathogenesis of atherosclerosis and coronary syndromes; moreover, various lines of evidence suggest that genetic factors contribute significantly to the risk of coronary artery disease (CAD). Through its effects on endothelial function, coagulation, insulin resistance and lipid metabolism, the proinflammatory cytokine TNF could be involved in cardiovascular pathophysiology. The aim of our study is to analyze whether TNF gene promoter (-308 G/A; -857 G/A) and TNF receptor polymorphisms (TNFR1 MspA1 I exon 1 and TNFR2 Nla III exon 6) show involvement in CAD predisposition in a group of Italian patients compared with healthy controls. Genotyping was performed by PCR-RFLP. Consecutive Italian patients with angiographically proven CAD (n= 248) were compared with controls (n=241), matched for age, sex and geographical origins. CAD patients showed a higher frequency of the TNF -308 A allele than healthy controls (p=0.046). After stratification according to risk factors for CAD, our analysis revealed that CAD patients with diabetes (p=0.042) and CAD patients without hypertension (p= 0.0495) displayed a higher frequency of the TNF -308 AA genotype compared with healthy controls. Our data stress the inflammatory nature of CAD and show a possible involvement of TNF -308G/A promoter polymorphisms in the predisposition to the development of this disease. The less frequent A allele seems to be a predisposing factor for development of CAD in particular pathological settings associated with the disease itself, such as diabetes. PMID- 17346439 TI - Human antibody and antigen response to IncA antibody of Chlamydia trachomatis. AB - The high prevalence of C. trachomatis worldwide has underscored the importance of identifying specific immunogenic antigens in facilitating diagnosis as well as vaccine development. The aim of this study is to evaluate IncA antibody and antigen production in natural human infections. Our temporal expression study showed that IncA transcription and protein expression could be detected as early as 4 hours after the start of infection. Antibody responses could be detected in urine and genital swab samples from C. trachomatis-positive patients. It is especially interesting to note that the IncA antigen could be detected in urine. In conclusion, we have identified IncA as an important antigen in human. The potential applicability of the IncA antibody or antigen in the diagnosis as well as to vaccine development for C. trachomatis is also discussed. PMID- 17346440 TI - Serum and mucosal cytokine profiles in patients with active Helicobacter pylori and ischemic heart disease: is there a relationship? AB - This study is designed to investigate, for the first time, circulating and gastric mucosal levels of IL1-alpha, IL-6, IL-8 and TNF-alpha in patients with ischemic heart disease (IHD) and matched controls, according to the presence or absence of active Helicobacter pylori infection. Furthermore, in order to evaluate whether modified lipid profile was associated to an increased cardiovascular risk, this was determined in the same groups. Cytokine levels were measured using ELISA in 58 patients with IHD and 52 controls. Active H. pylori infection was assessed if either culture of H. pylori or rapid urease test gave a positive result. Our findings indicate increasing cytokine mucosal levels in H. pylori-positive patients compared to H. pylori-negative subjects. However, the increase was statistically significant only for IL-6 and TNF-alpha in the gastric mucosa of IHD patients. In H. pylori-positive controls, IL-8 mucosal levels positively correlated with both IL1-alpha (r = 0.98; P = 0.0003) and IL-6 (r = 0.83; P = 0.03) levels. Circulating cytokine levels were comparable in IHD and healthy subjects, regardless of H. pylori status. There were no correlations between mucosal and circulating cytokine levels. Active H. pylori infection was not associated with a modified lipid profile in either controls or IHD patients, although ApoAI levels were significantly higher in H. pylori-positive controls compared to those H. pylori-negative. Taken together, the results of the present study provide evidence that active H. pylori infection may play a role as a trigger factor in the pathophysiology of IHD by inducing an inflammatory cascade concentrated on gastric mucosa. PMID- 17346441 TI - Lansoprazole increases serum IgG and IgM in H. pylori-infected patients. AB - Proton-pump inhibitors have been reported to influence the human immune system, we therefore evaluated the effect of lansoprazole, a proton-pump inhibitor, on humoral immunity. Patients with gastric ulcer received lansoprazole 30 mg/day for 8 weeks, and serum immunoglobulins were evaluated before and upon completion of the treatment. There were 79 patients with gastric ulcer; 51 were H. pylori infected and 28 were H. pylori-uninfected. Eighteen patients positive for H. pylori were receiving at least one non-steroidal anti-inflammatory drug, and 12 patients negative for H. pylori received one non-steroidal anti-inflammatory drug. H. pylori-infected patients showed significant increases in serum immunoglobulins G and M 8 weeks after the start of lansoprazole treatment (P<0.001 for IgG and P<0.01 for IgM), but uninfected patients did not. Even when H. pylori-infected patients receiving a non-steroidal anti-inflammatory drug or low-dose aspirin were analyzed separately, these increases were seen (P<0.001 for IgG and P<0.005 for IgM). Lansoprazole elevated serum levels of immunoglobulins G and M in gastric ulcer patients with H. pylori infection, particularly in those receiving non-steroidal anti-inflammatory drugs. Deducing from these observations, lansoprazole might alter the Th1 shift in the immune response induced by H. pylori infection. PMID- 17346442 TI - Ulcerative colitis masked by giant urticaria. AB - The occurrence of giant urticaria and ulcerative colitis is very infrequent. A 23 year-old female reported the initial eruption of short-lived cutaneous itchy weals on her arms. Then lesions ran together and became confluent, extending to her legs, followed by undefined abdominal pain and a slight increase of body temperature. Exams showed hystologically confirmed ulcerative colitis, with perinuclear anti-neutrophil cytoplasmic antibody positivity. Ulcerative colitis therapy led not only to the remission of the colitic symptoms, but also to the prompt recovery of skin manifestations. Urticaria was the epiphenomenon of ulcerative colitis. PMID- 17346443 TI - Penicillamine-related lichenoid dermatitis and utility of zinc acetate in a Wilson disease patient with hepatic presentation, anxiety and SPECT abnormalities. AB - Wilson's disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson's disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc-ECD-SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson's disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson's disease. Since most of Wilson's disease penicillamine treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson's disease therapy, and in particular to differentiate specific therapies for different Wilson's disease phenotypes. PMID- 17346444 TI - A novel treatment of contact dermatitis by topical application of phospholipase A2 inhibitor: a double-blind placebo-controlled pilot study. AB - Phospholipase A2 hydrolyzes membrane phospholipids releasing arachidonic acid and lysophospholipids. These are key precursors of inflammatory mediators, such as prostaglandins, leukotrienes, thromboxanes and PAF, in numerous inflammatory/allergic diseases, including skin inflammation. Accordingly, inhibition of PLA2 has long been postulated as a potentially potent anti inflammatory therapy. In the present study we tested the effect of a novel PLA2 inhibitor on contact dermatitis in human subjects. A double-blind, placebo controlled pilot study was conducted on contact dermatitis patients (n = 11) treated with the inhibitor-containing topical preparation (1% cream). Disease severity was assessed by physicians assessment before treatment (day 0) as well as after 14-days and 30-days. Patients treated with 1% PLA2 inhibitor-containing cream showed a 69.9% reduction in disease score while placebo-treated patients showed a reduction of 36.5% with p = 0.0024. The clear improvement in the disease score of inhibitor-treated patients supports the involvement of PLA2 activity in skin inflammation and the therapeutic prospective of its inhibition. PMID- 17346445 TI - Pulmonary exposure to diesel exhaust particle components enhances circulatory chemokines during lung inflammation. AB - This study examines the effects of DEP components on circulatory CC and CXC chemokines, potent activators and chemoattractants for macrophage and leukocyte subpopulations, in a murine model of lung inflammation. ICR mice were divided into six experimental groups which received intratracheal inoculation of vehicle, LPS alone (2.5 mg/kg), organic chemicals in DEP (DEP-OC: 4 mg/kg) extracted with dichloromethane, residual carbonaceous nuclei after the extraction (washed DEP: 4 mg/kg), DEP-OC + LPS, or washed DEP + LPS. Intratracheal instillation of each DEP component alone did not significantly change the circulatory level of macrophage inflammatory protein (MIP)-1alpha, MIP-2, and macrophage chemoattractant protein 1 (MCP-1) 24 h after the exposure as compared with vehicle instilled alone. In the LPS group, MCP-1, but not MIP-1alpha or MIP-2, was significantly greater than in the vehicle group. The combined administration of LPS and washed DEP caused a further three to five-fold increase in MIP-1alpha, MIP-2, and MCP-1 proteins in the serum as compared with LPS administered alone. No significant difference between the LPS + DEP-OC group and the LPS group was observed. These results indicate that pulmonary exposure to washed DEP enhances circulatory level of chemokines during lung inflammation. The enhancement may be important in the aggravations of systemic inflammatory responses and ischemic cardiovascular conditions associated with air pollution. PMID- 17346446 TI - Correlation between serum IgE and salivary cortisol levels in subjects with type I allergic disorders. AB - This study compares the relationship between serum IgE and salivary cortisol levels in 42 normal and in 18 type I allergic subjects. Levels of serum total IgE and salivary cortisol were determined with the UniCAP system and ELISA respectively. In the type I allergic subjects, there was a significant correlation between serum IgE and salivary cortisol levels (p < 0.01). In the normal subjects, on the other hand, no correlation was found. These findings suggest that there may be an association between stress and allergic disorders. PMID- 17346447 TI - Poly-L-lactic acid beta-tricalcium phosphate screws: a preliminary in vivo biocompatibility study. AB - The aim of this study is to assess the biocompatibility of two types of Poly-L lactic acid (PLLA) screws (with either hydroxyapatite (HA) or beta-tricalcium phosphate (beta-TCP)) implanted in the left femur of four sheep euthanized at 42, 50, 57 and 84 days after surgery. Titanium screws were also implanted for comparison purposes. No signs of inflammation were seen in the 240 specimens. A rating of "+/-" for macrophages and "-" for neutrophils was assigned to all specimens. All specimens were assigned a rating which ranged from "+/-" to "+++" for fibroblasts and osteoblasts. The presence of macrophages, neutrophils and fibroblasts/osteoblasts was not statistically different for the four implantation periods. PLLA implants with beta-TCP have a biocompatibility comparable to PLLA implants with HA. PMID- 17346449 TI - [Is oxidative stress important in medicine?]. PMID- 17346450 TI - [Hypoacusia as a result of chronic traumatic acoustic lesion in workers with affiliation to the Mexican Social Security Institute, 1992-2002]. AB - INTRODUCTION: Hypoacusia by chronic acoustic trauma (HTAC) is one of the main work diseases. OBJECTIVE: to analyze the distribution and frequency of hearing loss produced by chronic acoustic trauma (HLON) in workers who attend to Mexican Social Security Institute (IMSS). Also analyze the estimated cost of permanent work disabilities. MATERIAL AND METHODS: We analyze all hearing loss cases of the workers who attend to IMSS in the period between 1992 to 2001, registered in the Subsystem of registration of work's risk in the IMSS. Measures of central tendency, odds ratio (OR) and direct costs by means were calculated. RESULTS: The HLON represents 41% (1867) of all work's disease, during the period it was observed an increase of number of cases, the average of permanent disabilities, the rate of incidence and the average of rating percentage. The cases solved through a demand showed an increase to 105% in four years. The estimate monthly cost for every worker was 277 pesos. CONCLUSIONS: The HLON represents an important problem for the IMSS causing social and economic impact. If they don't take some actions to improve the quality of chronic acoustic trauma diagnosis it will have more serious consequences. PMID- 17346451 TI - [Family risk perception to diabetes mellitus]. AB - OBJECTIVE: To describe the relation between risk perception of people with relatives who have been hospitalized with diabetes mellitus, and also their modifiable risk factors. MATERIAL AND METHOD: We applied a validated questionnaire to a hundred of people who have any relatives with diabetes mellitus, because we wanted to know their perception for risk of this disease and their modifiable risk factors, as obesity, sedentary life style and meals. We think that the relatives who have two or more modifiable risk factors have a higher probability to develop diabetes mellitus than the relatives who have only one of them. RESULTS: The risk perception to develop diabetes in patients' relatives could be 87%; 67% has fat, and 73% has a sedentary life style. So, the relation among the modification of risk factors and the risk perception towards diabetes mellitus was not really significant (p = 0.399, RR 0.94, IC 0.80-1.10 to 95%), but there is a statistical relation among high risk for diabetes mellitus acquisition and gender (chi2 5.0, p < 0.05, RR 1.61, IC 1.00 < Rr -2.58), when we associate the variable age and obesity (chi2 7.9, p < 0.05, RR 0.59, IC 0.37 0.93). CONCLUSIONS: More of 50 % patients' relatives are in a high risk to develop diabetes mellitus because they have a similar life style than the patient had before getting the illness. For this reason, we suggest a different educational and cultural orientation in Mexico to identify all people in risk and do following of previous parameters about their health. PMID- 17346452 TI - [Results in short term of educational program "parents' school" about family environment]. AB - OBJECTIVE: Evaluation of effect in short term of the parents school program (PSP) about the family environment and the different results between participating and non-participating parents. MATERIAL AND METHODS: A cohort study was performed on 112 parents of students from the High School 5 (University of Guadalajara) during six months, 61 parents received the program (intervention group, IG) and 51 were the control group (CG). The program was made in 17 weekly interactive meetings, where the topics were: adolescent psychology and sexuality; parent-children relationship; family communication; self esteem; and addiction prevention. All of these topics were discussed. To evaluate family relationship the key word used was: How is your family relationship? RESULTS: There were found at baseline, a smaller family, and lesser family income in the IG. On the other hand, the CG showed higher scores on satisfaction with the academic and work performance; participation and problem solving; power, money and sex; and life satisfaction. At the end of the program, only 4% subjects of the IG and 59% of the CG were available for assessment. At this point we found that all differences have disappeared except life satisfaction, In addition new differences appeared as: in the control group there was a higher score for children's problems, and satisfaction with life. On the other hand, the IG showed an increased score on professional support searching, a lower score in parent-children communication. CONCLUSIONS: Our findings suggest that parents who voluntary received the PSP came from vulnerable families. The program improves the search for Professional support. PMID- 17346453 TI - [Hospital practice in neonatal period to prevent infant sudden death syndrome]. AB - OBJECTIVE: To describe hospital care for newborns in the Instituto Mexicano del Seguro Social (IMSS), as well as all the recommendations given to parents to prevent sudden infant death syndrome (SIDS) at home. MATERIAL AND METHODS: There were twenty-eight IMSS hospitals randomly selected from four geographical areas of the country, under a stratified sampling method according to the number of births per year. The method used was newborns direct observation in the neonatal care areas, and to fill out a questionnaire applied by trained observers. This questionnaire was adapted from the Maternity Advice Study that includes hospital care for newborns and all the recommendations that parents have to do for newborns at home. RESULTS: The newborns in neonatal areas used to sleep in lateral position (80 and 67%). Baby cradles with medium firmness and elevated head-rest were predominant in the areas surveyed. Babies were generally wrapped up from the neck to down, tightly enough that it prevented arm and leg movement. Parents received information on how to prevent SIDS at home, and up to 21% of them received no information at all. CONCLUSIONS: There were no specific practices at all the hospitals in this survey to diminish SIDS. It is necessary to organize specific health actions to diminish the risk of SIDS at home. PMID- 17346454 TI - [Deficient identification of signs and symptoms in Streptoccoci amigdalitis]. AB - OBJECTIVE: To evaluate the degree of identification of main signs and symptoms of streptococcal pharyngitis by resident doctors, general practitioners, family physicians and pediatricians. MATERIALS AND METHODS: A prospective, cross sectional and comparative study was done. A validated questionnaire was applied including the following topics: social demographic, main signs and symptoms, clinical cases; and clinical pictures. We interviewed resident doctors (n = 40), general physicians (n = 21), family physicians (n = 35) and pediatricians (n = 19) from different institutions (SSa, ISSSTE, IMSS) in Guadalajara, Mexico, from March to August 2005. Scores were interpreted as very good, good, regular and poor, and these scores were related with the specialty and clinical years of experience. STATISTICAL ANALYSIS: chi2, student t test and linear regression. RESULTS: This study included 115 physicians between 22 to 60 years old (mean = 39) and with 0 to 31 (mean = 10) clinical years of experience. Regarding the conceptual identification of main signs and symptoms, tonsil exudates were recognized by 33 to 61% of physicians, and a clinical case of streptococcal tonsillitis was recognized by 50 to 70%. A clinical picture of tonsil caseum was misinterpreted as streptococcal tonsillitis by 13 to 35% of the physicians. There was no association between years of clinical experience and the scores obtained in clinical cases (r = 0.20) or clinical pictures (r = 0.09). CONCLUSIONS: The clinical identification of streptococcal tonsillitis was regular to poor among all the interviewed physicians, and there had no correlation with the years of clinical experience. The reinforcement in teaching to recognize the key signs and symptoms of streptococcal tonsillitis at medical school would result in better recognition, more rational use of antimicrobials and reduction in health institutions costs. PMID- 17346455 TI - [Correlation between the level of work satisfaction and professional burnout in family physicians]. AB - OBJECTIVE: To determine the correlation between labour satisfaction and physician wear out. MATERIAL AND METHODS: There was a cross sectional study with all the family doctors from four Units of Family Medicine from Cancun (n = 102), with four or more years of medical practice. The questionnaire Red Font was used for labour satisfaction and Maslach Burnout Inventory for professional wear out, as well as the coefficient of correlation of Kendall. RESULTS: The predominant level of labour satisfaction was the medium (50.5%). the low level of wear out prevailed (50.5%). Medical doctors with medium or high satisfaction had low to medium wear out, and those who were reported with low satisfaction had moderate and high wear out. In the analysis bivariate between labour satisfaction and professional wear out the association was statistically significant, although there was not correlation (Kendall = -0.281). CONCLUSIONS: In contrast with other studies where they found an inversely proportional relationship, in this study any correlation was found. The ideal situation could be that all medical doctors develop high satisfaction and low professional wear of; however this didn't happen through this study. It is very important to study all the factors that have influence to elevate the professional wear of and dissatisfaction in our medical doctors to develop programs that allow to cope these problems. PMID- 17346456 TI - [Quality life in climateric women with and without hormonal replacement therapy?]. AB - OBJECTIVE: To compare quality of life in climacterical women with and without hormone replacement therapy. MATERIAL AND METHODS: A cross-sectional analytical study was carried out in the Family Medicine Unit number 61 in Veracruz, Veracruz. There were chosen 102 women between 40 and 60 years old. There were two groups: the first one with 51 patients with hormone replacement therapy during the last year; the second one with 51 patients who are not in hormone replacement therapy. Coop/wonca charts were used to measure quality of life. A complementary questionnaire related to climacteric period and menopause was answered by both groups. Statistical test with chi2 was carried out. RESULTS: Health condition and satisfactory sexual life were improved in patients with hormone replacement therapy (30 versus 19, p = 0.007; and 40 cases versus 30, p = 0.04, respectively). No significantly differences were found in six from seven coop/wonca charts. CONCLUSIONS: There were no impact results in climacteric and menopause women. However, a better health condition and satisfactory sexual life were observed in patients with hormonal replacement therapy. PMID- 17346457 TI - [Sex and age associated to femur and rotula fractures]. AB - OBJECTIVE: To identify specific fractures risks of the following bones: distal femur, patella and tibia plateau, according to sex and age, with special interest in women >or= 50 y.o. MATERIAL AND METHODS: An epidemiologic case-control study was done between January 2002 and December 2005. The incidence rate for fractures were got by year, sex and age. The group exposed to the risk factors, was represented by female patients >or=50 y.o. The cases with fracture's worst prognosis were: distal femur (supracondylar, supraintercondylar or condylar), tibial plateau (Schatzker IV-VI); the control group was made with patients which fractures were in: proximal femur (Subtrocantheric, diaphysis), tibial plateau (Schatzker I-III). Descriptive and inferential analysis were done separately and together. RESULTS: 1578 Patients were studied. Incidence of fractures in the studied regions was of 5.9 per 10 000 persons/year (py), being of 5.7 and 4.9 per 10,000 py for men and women, respectively (p < 0.001). In subjects with age >or=50 y.o. the incidence rate was of 10.5 and 6.6 per 10 000 py for men and women, respectively. In the study patients less than 50 y.o. the incidence rate was of 1.6 per 10 000 py for both sexes (p < 0.001). The women >or=50 y.o. presented an OR of 5.1 (95% CI: 2.7-9.8, p < 0.001). CONCLUSIONS: In this study sample, the risk of fracture of the femur and the knee was greater in men than in women. In the >or= 50 y.o. age group, the ratio was inverted, with special interest in distal femur fractures. According to sex and age, no differences were identified in tibia plateau fractures. PMID- 17346458 TI - [Right Bochdalek hernia and liver situs solitus in an adult. A clinical case]. AB - The Bochdaleck's hernia is an anatomical defect of posterolateral region of the diaphragm that lets abdominal structures go inside the thorax. It has an incidence of 1 in 2000 to 5000 of newborn alive, without difference of sex. This defect is very common in the neonatal period and rare in adult age. We present a case of a male patient 32 years old, with the definitive diagnosis of Bochdalek hernia. The diagnosis was made by radiographic findings, with a few digestive symptoms. Confirmatory diagnosis was made by axial tomography computerized that found part of bowel in right hemithorax and pulmonary hypoplasy, with liver in situs solitus. The patient received medical treated only. The patient did not receive surgical treatment because it is supposed that this kind of treatment has more risks than benefits. PMID- 17346459 TI - [The autopsy: a useless procedure nowadays?]. PMID- 17346460 TI - [Risk factors associated with intrauterine growth delay]. AB - INTRODUCTION: The term intrauterine growth delay (IGD) is used to refer a fetus with weight at birth lower than the 10th percentile for their gestational age. OBJECTIVE: to determine the prevalence and to identify risk factors associated with intrauterine growth delay in patients with normal fetal growth curves. MATERIAL AND METHODS: This study was made at General Hospital in Queretaro, Queretaro. There were included 70 obstetric patients with newborn with intrauterine growth delay (cases) and it was compared with 70 control patients with newborn without intrauterine growth delay. RESULTS: There were studied 70 cases of a total of 192 registered during the period of this study. There was a prevalence of 2.5. Of all the newborn with intrauterine growth delay, 40 (47.2%) were female and 30 (42.8%) were male, relating with age, mothers below 20 and above 30 were not show significant differences The risk factors associated were mainly inadequate pregnant women weight (OR 4.84, CI 95%=1.56 to 16.1) and less than five medical appointments for medical control during prenatal period (OR 6.0, CI 95%=2048 to 14.81) , hypertensive disease during pregnancy (OR 5.09, CI 95%=1.4 to 20.21) and cervicovaginal infections (OR 5.09. CI 95%=1.52 to 21.56). CONCLUSIONS: It is necessary to pay more attention to pregnant teenagers and also to general pregnant women to receive an adequate prenatal control in order to detect patients with risk of IGD and of this way to diminish morbidity and mortality in the newborn. PMID- 17346461 TI - [Professional burnout in family physicians and its association with social demographic and labor factors]. AB - OBJECTIVE: To determinate the prevalence of burnout in family physicians of the Family Medicine Units in the Estado de Mexico and its association with labor and socio demographics factors. MATERIAL AND METHODS: A transversal study was made in five Family Medicine Units. 154 physicians of both sex participated in this study. The Maslach Burnout Inventory (MBI) which measures the burnout in its three dimensions: emotional fatigue (EC), depersonalization (DP) and personal realization (PR), was applied by self-administration. Socio-demographic and labor details were obtained. RESULTS: Response rate was 85. A high CE was significantly associated to inadequate physical area, OR 3.9 CI 95% 1.5-10.6; to work load OR 7.6 CI 95% 1.6-50.7 and to lack of labor incentives OR 4.4 CI 95% 1.7-11.9 depersonalization was associated only with salary OR 2.6 CI 95% 1.05-6.4. CONCLUSIONS: Family physicians of Mexican Institute of Social Security have labor factors that are associated with burnout that can affect patient's attention. PMID- 17346462 TI - [Depression's prevalence and risk factors in hospitalized seniors]. AB - OBJECTIVE: To determine the prevalence of depression and associated factors in hospitalized seniors. MATERIALS AND METHODS: A prospective and transversal study was made in female and male seniors at General Hospital number 16 of the Mexican Institute of Social Security in Torreon, Coahuila, Mexico between June and December of 2003. There were applied Yesavage, Katz, Lawton and Folstein scales. RESULTS: There were included 320 patients with a mean age of 72 years. Ten patients with dementia (prevalence of 3.1%) were excluded. Depression was found in 50% and dependence in 62% according to Katz index, and 75% of the patients had dependence in daily life activity according to the Lawton scale. In the bivariate analysis, the following variables were associated with depression: age over 80, female gender, patients that have been hospitalized in the internal medicine department, living alone, to be dependent, and to have a chronic illness. In the multivariate analysis using logistic regression four former variables (female sex, living alone, dependence, and to be hospitalized in Internal Medicine department) had a significant association. CONCLUSIONS: The prevalence of depression among hospitalized older patients is high. The strongest factors associated were dependence of other people and to have chronic disease. PMID- 17346463 TI - [Clinical control after diabetic and hypertension therapy group sessions]. AB - INTRODUCTION: To get good results in the treatment of chronic diseases, we need the participation of patients who take decisions, where education is the most relevant factor. We analyze the limits and impact of an educational strategy during six group sessions through a month. OBJECTIVE: To evaluate clinical control in patients with diabetes and hypertension after group sessions. MATERIAL AND METHODS: It was included a group of 172 patients with diabetes and hypertension who went to a help group in 2003; There were two groups, a Group A with 88 patients who finished the educational strategy and a group B with 88 patients who left after the second session. RESULTS: The group A diminish glucose average -82 mg/dL (p<0.0001) and also lowered the systolic arterial tension -11.7 mm Hg (p<0.0001) and the diastolic tension -6.9 mm Hg (p<0.0001); there were not significant changes in group B. We used a repeated measured model 4 months before, during and 4 months after educational strategy, and there was a difference between the groups (p=0.008) and also the persistent effect after the educative strategy. CONCLUSION: We consider that improvement in clinical control was associated with the strategy used, because education motivate patients to take decisions to face real problematic situations, and helps them to think over life circumstances, and to have health live styles to control both diabetes and hypertension. PMID- 17346464 TI - [Growth in weight and height in children less than two years old in the IMSS]. AB - OBJECTIVE: To describe the physical growth in weight and height of children less than two years of age cared for the Mexican Institute of Social Security (IMSS). MATERIAL AND METHOD: A population-based National Survey, which was also regional representative, was carried out in Ordinary Regime (RO) and the IMSS Oportunidades Program (IO). In two years (2000-2002) the study gathered data on 17,502 children from the RO and 9872 from IO. The measures of weight and length were made by nurses, according to WHO criteria. Growth is reported as weight and length for each month of age and gender, in tables and percentile curves derived from quintile regressions, using a third degree polynomial to smooth out the lines. RESULTS: The trends of the means of weight and height in the first two years of life in children cared by Instituto Mexicano del Seguro Social show a pattern similar to those described in healthy children in other populations. However, the values are lower than those obtained in developed countries. CONCLUSIONS: Children's growth at two years of age at the Instituto Mexicano del Seguro Social shows a curve that is lower than that of the reference population recommended by the World Health Organization as an international standard. PMID- 17346465 TI - [Associated factors to severe sport injuries]. AB - OBJECTIVE: To identify the risk factors associated to severe sport injuries. MATERIAL AND METHODS: Case-control study, with non probabilistic of consecutive sample cases. The risk factors criteria for severe injuries were established by experts' consensus in patients diagnosed with injury caused during sports practice between July 2004 and March 2005. These patients were attended in the emergency room at the Magdalena de las Salinas High Medical Specialty Unit in Mexico City. RESULTS: There were included 131 patients with sport injuries; there were 76.3% men and 23.7% women. The mean age was 21.6+/-8.6. There were non severe injuries, (concussions, muscle strains, sprained) in 55% of patients and 45% of patients had severe injuries (fractures, dislocation, fracture dislocation, physeal injury). In the case of severe injuries, it was associated with working out in a non reglamentary area [odd ratio (OR) of 2.5, p=0.01, CI (1.2-5.1)], soccer practice [OR of 2.4, p=0.01, CI (1.2-4.8)], body axis injury [OR of 5.9, p=0.004, CI (1.6-21.9)], indirect injury mechanism [OR of 2.2, p=0.04, CI (0.9-5.2)], sport practice0.05). CONCLUSIONS: The EAE measurement is an easy, and low cost test that can be used to make the universal hearing screening accessible. These results support the normal levels of EAE and the Corti organ function in healthy newborns. PMID- 17346468 TI - [Actual autopsy functions: perceptions and opinions of postgraduate training physicians on oncology specialities]. AB - INTRODUCTION: How the physician situates the autopsy among the elements to improve the clinical performance is related to the possibility that he or she requests it to the patient's family and that they authorize it. OBJECTIVE: To explore the perceptions and perspectives that medical post graduate trainees on oncology specialities have of the potential current functions of the autopsy. MATERIAL AND METHODS: A semi-structured written questionnaire with four questions was applied to residents in surgical oncology, medical oncology and radio oncology. RESULTS: 34 medical residents were invited and all of them participated. 100% of the residents had an expectative of improvement in the clinical practice if more autopsies were done. The more frequent reasons to justify this expectative were: to establish the definitive diagnosis in controversial or poorly defined cases in 47% and the contrast between clinical and necropsy diagnosis, in 38%. The concept of the autopsy as a resource to evaluate the quality of the everyday clinical diagnosis was excluded by 59% of the residents. CONCLUSIONS: The autopsy is frequently visualized by the medical residents as a procedure which utility is limited to the solution of diagnostic discrepancies in selected cases. This situation could impede its function as a reference for the critique of clinical diagnoses and for the detection of medical errors in the more habitual cases in a specific setting and whose diagnosis is not controversial. PMID- 17346469 TI - [Correlation between ultrasound and surgery in supraspinal and interspinal ligaments injuries]. AB - INTRODUCTION: The spinal fractures associated with posterior complex ligament injury are highly unstable, they require surgical stabilization and with frequency they can not do the diagnosis through imaging methods as radiography or computed tomography scan. Ultrasound is a no invasive imaging method that lets the visualization of the spinal posterior complex ligament and it also allows to see spinal fractures with or without ligament injury. OBJECTIVES: To correlate preoperative physical, radiographic and ultrasound findings with direct visualization of the posterior complex ligament, showing the diagnostic accuracy of the tests above mentioned regarding to detection of posterior complex ligament injury associated with thoracolumbar spinal fractures. MATERIAL AND METHODS: Fourteen patients with thoracolumbar fractures were evaluated by palpation of the interspinous gap, plain radiography and ultrasound before surgical treatment by a posterior approach. During the operation, posterior ligament complex injury was carefully examined. RESULTS: A wide interspinous gap was palpated in four patients and was found in 5 patients by radiography. Ultrasound examination showed ligament injury in 8 patients and integrity in 6. There was a significant relation between ultrasound findings and surgical results. CONCLUSION: Ultrasound is a highly sensitive and specific method to evaluate supraspinous and interspinous ligament injury in patients with thoracolumbar fractures, with superior diagnostic accuracy than physical exploration and radiographic evaluation. PMID- 17346470 TI - [Appropriate use of diagnostic esophagogastroduodenoscopy and its relation with positive results]. AB - INTRODUCTION: Upper gastrointestinal endoscopy is a sensitive and safe procedure, but expensive and with certain risks. The range of inappropriate use of upper gastrointestinal endoscopy in open access system is between 5.6 to 61.7%. In our department we use restricted access system. OBJECTIVE: To determine the accuracy of Gastrointestinal Endoscopy American Society guidelines in the diagnosis through the upper gastrointestinal endoscopies performed in a reference hospital setting with restricted access. METHODS: We review requests for diagnostic upper gastrointestinal endoscopies and their reports between March 1st 2003 and February 29th 2004. It was defined as an appropriate diagnostic esophagogastroduodenoscopy which followed the American Gastrointestinal Endoscopy society guidelines. It was done statistical descriptive analysis. RESULTS: A total of 3033 requests and reports of upper gastrointestinal endoscopies were reviewed. The proportion of clinical diagnoses that followed the guidelines was 74.3%. We found a 56.3% of abnormal positive endoscopy findings, concordance between clinical diagnosis and abnormal positive endoscopy findings was 46.8%. CONCLUSION: The proportion of upper gastrointestinal endoscopies that follow the American Gastrointestinal Endoscopy Society guidelines in our restricted access system is low. PMID- 17346472 TI - Rebranding. PMID- 17346471 TI - [Prescription of temporal disability certificates in workers attending to IMSS from the perspective of health economy]. AB - The repercussion of health-disease state on social life or individual includes his/her work performance. In many countries, social security is one of the options for diffusing and buffering the impact of the disease. This paper is focused on the analysis of the unjustified prescription of temporary sick leave certificates (CITT), which combines the social security medical components and economic benefits (subsidies). The objective is to analyze the mechanism of prescription of CITT from the perspective of health economics and health care services. The detailed flow of CITT at the Mexican Institute of Social Security is described, as are some concepts of the health economics perspective that contribute to explain the prescription of CITT. Statistical data of sick leaves due to work-related and non-work-related diseases are presented from the institutional perspective. Finally, it is emphasized that although CITT are a medical prescription, it is advisable to take into account the economic perspective and its concepts in order to achieve an efficient use of resources. PMID- 17346473 TI - An alternative method to deliver the impacted head at caesarean section. PMID- 17346474 TI - Maternal leukocytosis after preterm premature rupture of membranes and infant neurodevelopmental outcome: a prospective, population-based study (Decrire L'ouverture des Membranes Inopinee le Nouveau-ne et l'Organisation des Soins [DOMINOS] Study). AB - OBJECTIVE: To evaluate the relationship between maternal leukocytosis in women admitted after preterm premature rupture of the membranes (PPROM) and the neurodevelopmental outcomes of their infants at two years of age. METHODS: A prospective cohort study of women with PPROM occurring between 24 weeks and 33 weeks and 6 days of gestation was conducted in a region of France over two years. The primary outcome was a composite of neurodevelopmental variables, including motor impairment (an inability to stand without support, walk, run, or climb or descend stairs alone), auditory impairment, visual impairment, or the presence of monoplegia, diplegia, or hemiplegia at two years of age. Multiple logistic regression analysis was used to adjust for confounding factors. RESULTS: Of 394 cases, 6/64 neonates (9.4%) born to mothers with leukocytosis were no longer alive at the two-year follow-up, compared with 14/330 (4.2%) born to mothers with no leukocytosis (P = 0.09). At two years of age, 28 (56%), 22 (52%), 34 (49%), and 52 infants (37%) showed at least one of the primary outcome features for PPROM occurring at 24-27, 28-29, 30-31, and 32-33 weeks' gestation, respectively. In univariate analysis, PPROM at less than 30 weeks, leukocytosis, and cerclage were associated with a higher rate of the primary outcome. In logistic regression analysis, only leukocytosis remained significant (odds ratio [OR] 2.92; 95% confidence intervals [CI] 1.33-6.39, P = 0.02). Fewer infants whose mothers had a leukocyte count (WBC) .15 000/mm3 at the time of PPROM showed a feature of the primary outcome at two years of age than infants whose mothers had a higher WBC (P < 0.01). CONCLUSION: Maternal leukocytosis at admission is associated with higher adverse infant neurodevelopmental outcomes at two years of age. Guidelines for the management of women with PPROM who do not begin to labour should include consideration of the degree of leukocytosis. PMID- 17346475 TI - A randomized controlled trial of a bedside partogram in the active management of primiparous labour. AB - OBJECTIVE: The partogram is a pictorial representation of the progress of labour, used in an effort to enhance early recognition of dystocia and help avoid Caesarean section (CS). The objective of this study was to evaluate the effect of partogram use on the CS and obstetric intervention rates. METHODS: We conducted a randomized controlled trial of use of the partogram in 1932 primiparous women with uncomplicated pregnancies at term. Patients were randomly assigned to one of two groups: the standard group, who had the progress of labour charted in written notes, or the partogram group, whose progress in labour was recorded using a bedside graphical partogram as well as in written notes. Outcomes were stratified according to whether labour was spontaneous or induced and whether membranes were initially intact or ruptured. The primary outcome was the rate of CS; secondary outcome measures were rates of obstetric intervention for dystocia. RESULTS: There was no significant difference between the groups in rates of CS (partogram 24%, standard notes 25%), rates of other interventions, amniotomy, oxytocin use, or the mean cervical dilatation in labour. CONCLUSION: In this study, the use of a partogram without a mandatory management of labour protocol had no effect on rates of CS or other intrapartum interventions in healthy primiparous women at term. PMID- 17346476 TI - The effect of second-trimester antibiotic therapy on the rate of preterm birth. AB - OBJECTIVE: As many as 50% of spontaneous preterm births are infection-related, with Mycoplasma species being the most common microbial isolates from the amniotic cavity. The goal of our study was to evaluate the effect of macrolides, a specific group of antibiotics known to be effective against Mycoplasma species, on the rate of preterm births. METHODS: We performed a systematic review of the literature and a meta-analysis. We searched PubMed, Medline (1965-March 2006), Embase, and the Cochrane Library, using the key words "pregnancy," "macrolides," "erythromycin," "azithromycin," and "clarithromycin." The research was limited to randomized controlled trials and to human females. Studies included for analysis were of women in the second trimester of pregnancy who received either macrolides or placebo (or no treatment) in order to prevent preterm delivery with at least 95% of patient follow-up. We excluded studies involving women with preterm premature rupture of membranes or regular uterine contractions. Meta-analysis of the retrieved data was performed using RevMan 4.2.8 (Cochrane Collaboration) with dichotomous analyses and delivery prior to 37 weeks' gestation as the primary outcome. The analysis was subsequently repeated using the same methodology for clindamycin and metronidazole administered during the second trimester. RESULTS: Of the 61 articles yielded by our search, three original papers, investigating a total of 1807 women, examined macrolide utilization and met our criteria. Women included in our analysis were all considered to be at higher risk for preterm delivery (vaginal fetal fibronectin positivity, urogenital Mycoplasma infection, prior preterm delivery, and/or pregestational maternal weight < 50 kg). Compared with placebo, macrolides were associated with a lower rate of preterm births (odds ratio [OR] 0.72; 95% confidence intervals [CI] 0.56-0.93), as was clindamycin (OR 0.68; 95% CI 0.49-0.95). On the other hand, metronidazole (OR 1.10; 95% CI 0.95-1.29) was not linked with significant changes in the rate of preterm births. A higher rate of preterm delivery was found when mid-trimester metronidazole was the only antibiotic administered (OR 1.31; 95% CI 1.08-1.58). CONCLUSION: Macrolides and clindamycin, given during the second trimester of pregnancy, are associated with a lower rate of preterm delivery, whereas second trimester metronidazole used alone is linked with a greater risk of preterm delivery in a high-risk population. Use of metronidazole, a common treatment for bacterial vaginosis and Trichomonas vaginalis, should be avoided during the second trimester of pregnancy in this population. PMID- 17346477 TI - Clinical management recommendations for surveillance and risk-reduction strategies for hereditary breast and ovarian cancer among individuals carrying a deleterious BRCA1 or BRCA2 mutation. AB - BACKGROUND: In Canada, there are wide variations in services for patients at risk for hereditary breast and ovarian cancer (HBOC), and clinical interventions and recommendations differ between regions and/or provinces. National strategies for the clinical management of HBOC exist in the United Kingdom, France, and Australia, and clinical programs in Canada would benefit from similar national recommendations and a consistent approach to clinical management. The National Hereditary Cancer Task Force developed recommendations to address the clinical management of patients at high risk of HBOC and related cancers. These recommendations are based on current practice in high-risk cancer clinics that provide care for individuals with known BRCA1 or BRCA2 mutations. METHODS: Canadian consensus recommendations were generated by the National Hereditary Cancer Task Force and compared mainly with two recently published guidance documents on the clinical management of women with increased risk of HBOC, one from the United Kingdom and the other from France. After review of these documents and the associated supporting scientific evidence, the Canadian consensus recommendations were modified and rated using predefined criteria. CONCLUSIONS: These recommendations pertain to (1) surveillance options including breast self-examination, clinical breast examination, breast surveillance by imaging, ovarian cancer surveillance, and surveillance for men; (2) risk reduction strategies including prophylactic mastectomy, prophylactic salpingo oophorectomy, and pharmacoprevention; and (3) the use of exogenous hormones. Regular updates should occur as new evidence becomes available. PMID- 17346478 TI - Interim statement on HPV immunization. PMID- 17346480 TI - Vanishing Canadians. PMID- 17346481 TI - Treatment of bacterial vaginosis in pregnancy: a new perspective. PMID- 17346482 TI - Preterm labour and birth: a survey of clinical practice regarding use of tocolytics, antenatal corticosteroids, and progesterone. AB - OBJECTIVES: We wished to determine prescribing practices of obstetricians in Canada regarding tocolytics, antenatal corticosteroids, and progesterone for women at increased risk of preterm labour and birth, and to determine whether these practices changed between 1997-98 and 2004. METHODS: Two cross-sectional surveys of Canadian obstetricians were conducted. The initial survey was in 1997 98 (N = 1313); the follow-up survey was in 2004 (N = 1508). RESULTS: Response rates were 46.4% in 1997-98 and 43.3% in 2004. Most respondents reported that they prescribed tocolytics to women with signs and symptoms of preterm labour (97.4% in 1997-98; 92.2% in 2004; P < 0.001) but use had decreased. In 1997-98, 20.0% of respondents used tocolytics for > 48 hours during one course of treatment, whereas in 2004, only 9.6% did this (P = 0.06). The tocolytic prescribed most frequently was magnesium sulphate in 1997-98 (40.6% of respondents), whereas in 2004, it was indomethacin (47.5% of respondents). The use of repeat courses of antenatal corticosteroids decreased from 72.9% in 1997 98 to 18.7% in 2004 (P < 0.001). In 2004, only a few respondents (7.0%) prescribed progesterone for women at increased risk of preterm birth. CONCLUSIONS: Most Canadian obstetricians continue to use tocolytics for women in preterm labour, although use has decreased over time, and the most frequently prescribed tocolytic has changed from magnesium sulphate to indomethacin. The use of repeat courses of antenatal corticosteroids decreased substantially during this time, and in 2004, progesterone was not in frequent use. PMID- 17346483 TI - Cost-effectiveness analysis of treatment strategies for Stage I and II endometrial cancer. AB - OBJECTIVE: Practice patterns vary across Canada with respect to indications for surgical staging and adjuvant radiotherapy in early endometrial cancer. We evaluated the cost-effectiveness of two common strategies for managing early endometrial cancer as part of an Ontario population-based study. METHODS: A decision-analytic model (DATA 4.5) was developed for Stage I and II endometrioid type cancer using empiric data from Ontario. On the basis of preoperative biopsy grade, one of two surgical procedures was selected: (1) hysterectomy and bilateral salpingo-oophorectomy (HBSO) or (2) surgical staging (HBSO and pelvic +/- para-aortic lymphadenectomy). Adjuvant radiotherapy (RT) was administered according to final grade and stage. After HBSO, pelvic RT was indicated for Grades 1 and 2 if Stage IC, IIA with > 50% myometrial invasion (MI), or IIB, and for Grade 3 if Stage IB, IC, IIA, or IIB. After staging, pelvic RT was indicated for Grades 1 and 2 if Stage IIB, and for Grade 3 if Stage IC, IIA with > 50% MI, or IIB. Main outcome measures were quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER). Sensitivity analyses were used to evaluate uncertainty around various parameters. RESULTS: The most cost-effective (dominant) strategies were determined for each preoperative grade. For Grade 1, HBSO strongly dominated surgical staging. For Grade 2, neither strategy was dominant; surgical staging had an ICER of $5216 per QALY. For Grade 3, surgical staging strongly dominated HBSO. These results were stable over a wide range of estimates for costs and utilities (i.e., patient preferences for a particular health state). CONCLUSION: The most cost-effective treatment strategies for early endometrial cancer in Ontario differ according to preoperative grade. PMID- 17346484 TI - Is gentamicin ototoxic to the fetus? AB - BACKGROUND: Gentamicin is used in pregnancy to treat infections that cause complications to the mother and fetus if left untreated. In 2003, Schering, the manufacturer of Garamycin Injectable, amended the product monograph in the Compendium of Pharmaceuticals and Specialties to state that gentamicin should be avoided in pregnancy due to cases of "total irreversible bilateral congenital deafness" in babies exposed to gentamicin in utero. Because we have identified, after an intensive literature search, only two cases over many years of availability, it is questionable whether the outcome can be attributed to drug use rather than other factors. OBJECTIVES: The main objective of this study was to determine whether any infant exposed in utero to intravenous gentamicin and born between January 2002 and April 2006 at Victoria General Hospital demonstrated audiologic deficits on routine hearing testing. Such testing has been universally available since late 2001. Our secondary objectives were to examine patterns of gentamicin use, including indication, dosage, duration, and to determine whether or not monitoring of serum gentamicin levels was done. METHODS: Women who had received gentamicin were identified through pharmacy records and their charts reviewed for factors that might contribute to fetal deafness including substance abuse, use of other potentially ototoxic medications, genetic predisposition, and intrauterine infections. We reviewed audiology test result and the infants' charts for potential confounding factors, including prematurity, low birth weight, low Apgar scores, anoxia, hyperbilirubinemia, sepsis, and meningitis. RESULTS: Fifty-two charts were reviewed, 40 of which documented live births. There was no case of hearing loss documented. Of the eight fetal losses, six (11.5%) were preterm births before viability, and two were elective terminations. Pyelonephritis was the main indication for gentamicin use (48%), followed by chorioamnionitis (31%) and other miscellaneous indications (21%). Three times daily dosing was used for a mean duration of 2.7 +- 2.3 days, resulting in an average cumulative dose of 764 +- 600 mg gentamicin. The average gestational age at exposure was 28 weeks. Maternal serum gentamicin levels were obtained in 72.5% of cases, and no trough level was above 2 mg/L. Other potentially ototoxic medications were administered to the mother in 17.5% of pregnancies, and to 17.5% of babies in the immediate newborn period. With the exception of one infant who died before additional testing could be carried out, all the infants passed hearing tests, 89% on initial screening. CONCLUSION: In utero exposure to gentamicin did not cause an increase in audiologic impairment in the infants tested in this cohort. PMID- 17346485 TI - Prenatal screening for fetal aneuploidy. AB - OBJECTIVE: To develop a Canadian consensus document with recommendations on maternal screening for fetal aneuploidy(e.g., Down syndrome and trisomy 18) in pregnancy. OPTIONS: Pregnancy screening for fetal aneuploidy started in the mid 1960s, using maternal age as the screening test. New developments in maternal serum and ultrasound screening have made it possible to offer all pregnant patients a non-invasive screening test to assess their risk of having a fetus with Down syndrome or trisomy 18 to determine whether invasive prenatal diagnosis tests are necessary. This document will review the options available for non invasive screening and make recommendations for Canadian patients and health care workers. OUTCOMES: To offer non-invasive screening for Down syndrome or trisomy 18 to all pregnant women. Invasive prenatal diagnosis would be limited to women who screen above a set risk cut-off level on non-invasive screening or pregnant women who will be 40 years at time of delivery who, after counselling, chose to go directly to amniocentesis/chorionic villi sampling (CVS). Currently available non-invasive screening options include maternal age combined with (1) first trimester screening (FTS) (nuchal translucency,maternal serum biochemical markers); (2) second trimester serum screening; or (3) two-step integrated screening, which includes first and second trimester serum screening with or without nuchal translucency (IPS, Serum IPS, contingent and sequential). These options are reviewed and recommendations are made. EVIDENCE: A MEDLINE search was carried out to identify papers related to this topic that were published between 1982 and 2006. Practices across Canada were surveyed. A consensus document was drafted and reviewed by committee members. VALUES: The quality of evidence and classification of recommendations followed discussion and consensus by the combined committees of SOGC (Genetics, Diagnostic Imaging)and CCMG (Prenatal Diagnosis). BENEFITS, HARMS, COSTS: These guidelines are intended to reduce the number of amniocenteses done when maternal age is the only indication. This will have the benefit of reducing the numbers of normal pregnancies lost because of complications of invasive procedures. Any screening test has an inherent false positive rate,which may result in undue anxiety. A detailed cost-benefit analysis of the implementation of this guideline has not been done, since this would require health surveillance and research and health resources not presently available; however, these factors need to be evaluated in a prospective approach by provincial and territorial initiatives. PMID- 17346486 TI - Hormonal contraception and breast cancer: keeping perspective. PMID- 17346487 TI - Women's views of elective primary caesarean section. PMID- 17346488 TI - The ALARM and MORE(OB) programs. PMID- 17346489 TI - Conservative treatment of urinary incontinence. PMID- 17346490 TI - Effect of regulatory changes on the frequency of emergency department visits to request prescriptions for emergency contraception. PMID- 17346491 TI - The role of the Doran Building in puerperal fever in Canada. AB - The Doran Building at the Kingston General Hospital, opened in 1894, represents an early Canadian initiative to apply the principles of sanitation, antisepsis, and asepsis to prevent puerperal fever ina freestanding lying-in hospital. This initiative was a response to maternal mortality during the 17th and 18th centuries, when approximately half of maternal deaths were due to puerperal fever. During the 250 years leading up to 1890, an understanding of the clinical nature of puerperal fever, its cause, mode of spread, and means of prevention had gradually developed. Despite this progress, puerperal fever remained a major cause of maternal mortality in the latter part of the 19th century. The Doran Building is a compact example of a pavilion hospital,built as a freestanding facility for women and children, with its own staff. Kenneth Fenwick, who was Professor of Obstetrics and Gynaecology at Queen's University and a vigorous advocate of sanitation, antisepsis, and asepsis, established the principles of patient care in the Doran Building during the period 1894 to 1928.His goal was the prevention of maternal mortality due to puerperal fever. During this period, there was a modest increase in the number of deliveries each year to a total of 3111 by 1928. There were 26 direct and indirect maternal deaths, representing a maternal mortality rate of 8.25 per 1000 live births. Puerperal fever accounted for the deaths of three women: one who had delivered in hospital and two who had delivered in the community and had been admitted following delivery. The application of the principles of isolation, sanitation, antisepsis, and asepsis limited the mortality in hospital due to puerperal fever in a manner consistent with the best hospitals elsewhere at that time. PMID- 17346492 TI - Visualization of the ovaries in early pregnancy by transvaginal sonography. AB - OBJECTIVE: To determine the frequency of visualization of the ovaries by transvaginal sonography (TVS) in a group of women in early pregnancy and to determine the onset of a decrease in sonographic visualization of the ovaries during this time. METHODS: The study population included all patients with an intrauterine pregnancy confirmed by the presence of a yolk sac,embryo, or fetus. The biometric data included crown-rump length and/or gestational sac mean diameter corresponding to < - 14 weeks' gestational age (GA). RESULTS: The study population included 11,095 women, of whom 1972 (17.8%) had a GA < - 6 weeks, 4665 (42.0%) 6.1 to 8 weeks, 2782 (25.1%) 8.1 to 10 weeks, 1208 (10.1%) 10.1 to 12 weeks, and 468 (4.2%) 12.1 to 14 weeks. At least one ovary was identified in 11,043 women (99.5%), and both ovaries were identified in 10,620 women (95.7%). Only the right ovary was identified in 274 women (2.5%), and only the left ovary was identified in 149 women (1.3%). In 52 women (0.5%), neither ovary was identified. Both ovaries were identified in 1929 pregnancies of < - 6 weeks' GA (97.8%), in 4528 between 6.1 and 8 weeks' GA (97.1%), in 2664 between 8.1 and 10 weeks, GA (95.8%), in 1114 between 10.1 and 12 weeks' GA (92.2%), and in 385 between 12.1 and 14 weeks' GA (82.3%). CONCLUSION: Transvaginal sonography achieved an overall visualization of one or both ovaries in 99.5% women with pregnancies of < - 14 weeks, GA. Both ovaries were visualized in 95.7% of women. A significant decline in ovarian visualization occurred after 10 weeks' GA. The results provide reference data on the likelihood of ovarian visualization in early pregnancy. PMID- 17346493 TI - Factors associated with postpartum urinary/anal incontinence in primiparous women in Quebec. AB - OBJECTIVE: To identify the factors associated with urinary incontinence (UI), anal incontinence (AI), and combined UI and AI (UI/AI) in primiparous women in Quebec at six months postpartum. METHODS: A questionnaire was mailed to 2492 primiparous women at six months postpartum to collect data on incontinence status, sociodemographic characteristics, elimination habits, lifestyle, and severity index scales. Obstetric characteristics were obtained via Quebec's Med Echo databank. Pearson chi-square, t test, analysis of variance, univariate regression, and stepwise modelling techniques were used for data analysis. RESULTS: The prevalence of UI in responders was 29.6%, of AI, 20.6%, and of combined UI/AI, 10.4%. Significant adjusted odds ratios were (1) for UI, English spoken (2.04 [95% confidence intervals 1.13-3.69]) and shoulder dystocia (2.90 [1.09-7.69]); (2) for AI, age > 35 years (2.13 [1.12-4.03]), duration of second stage of labour (1.67 [1.11-2.51]), and third or fourth degree tears (4.00 [2.32 6.89]); and (3) for UI and AI, age (2.00 [1.04-3.83]), English spoken (2.55 [1.25 5.19]), shoulder dystocia (4.91 [1.76-13.71]), instrumental delivery (2.28 [1.30 3.99]), third or fourth degree tears (3.58 [1.95-6.57]), and episiotomy (2.24 [1.162-4.33]). Caesarean section was associated with less UI (0.45 [0.28-0.72]), and smoking was associated with less AI (0.38 [0.19-0.76]). CONCLUSION: Combined UI/AI is associated with several obstetrical factors. The association of UI and AI is observed more frequently after complicated delivery (requiring the application of forceps) or involving perineal damage and episiotomy. As most of the identified factors are modifiable, a preventive treatment policy is advisable. PMID- 17346494 TI - Maternal decisions regarding prenatal diagnosis: rational choices or sensible decisions? AB - The premise underlying prenatal testing is that knowing the health status of the fetus will enable expectant parents to make rational reproductive decisions. Accordingly, rational-choice perspectives have informed both counselling protocols and the majority of investigations into the psychological processes involved in making decisions about testing and selective abortion. However, because conditions inherent in the testing situation may not adhere to the basic assumptions of rational choice models, the use of these models may be inappropriate. The individualistic focus of rational choice models may be too narrow to encompass the social and psychological factors relevant to making a decision about testing. In light of these limitations, we make a case for adopting a contextual framework for conceptualizing decisions regarding the use of prenatal testing. PMID- 17346495 TI - Removal of a non-communicating horn may not affect persistence or recurrence of endometriosis: a case report. AB - BACKGROUND: Retrograde menstruation is thought to initiate and potentiate endometriosis in women with non-communicating uterine anomalies. The effect of removing a non-communicating uterine horn on the persistence or recurrence of endometriosis is unknown. CASE: A 29-year-old woman with a non-communicating uterine horn and endometriosis underwent surgical removal of the non communicating horn with cautery of the endometriosis. A laparoscopy done two years later showed endometriosis similar in stage to that found at the initial procedure. CONCLUSION: Removal of a non-communicating uterine horn in a woman with endometriosis did not reduce the risk of persistence or recurrence of the disease. PMID- 17346496 TI - A report on best practices for returning birth to rural and remote aboriginal communities. AB - BACKGROUND: During the last four decades, policies and practices based on modern obstetrical techniques and knowledge have replaced traditional practices in many rural and remote Aboriginal communities. As most of these communities do not have obstetrical facilities or staff, women often have to leave their communities to give birth. OBJECTIVE: To review policies currently in place in Aboriginal communities that recommend evacuation of all pregnant women at 36 to 37 weeks' gestation to deliver in a Level 2 hospital. OPTIONS: Allowing Aboriginal women, their families, and their communities to decide whether it is safe and practical for women to deliver close to home. OUTCOMES: Increased opportunities for Aboriginal women in remote and rural communities to deliver within their own communities or closer to home in a familiar environment. EVIDENCE: PubMed was searched for articles on subjects related to birth in Aboriginal communities, birth in rural and remote communities, and midwifery in Aboriginal and remote communities. The web sites and libraries of the National Aboriginal Health Organization, The First Nations and Inuit Health Branch, and Health Canada were also searched for relevant documents. In addition, the authors visited three communities that have trained local midwives and that support deliveries within the community to observe and participate in their programs. BENEFITS: It is hoped that improved communication between health institutions and remote and rural communities and changes in policies and procedures concerning the care of pregnant women in these communities will contribute to reductions in perinatal morbidity and mortality. SPONSORS: First Nations and Inuit Health Branch (FNIHB), Health Canada. RECOMMENDATIONS: 1. Physicians, nurses, hospital administrators, and funding agencies (both government and non-government) should ensure that they are well informed about the health needs of First Nations, Inuit, and Metis people and the broader determinants of health. 2. Aboriginal communities and health institutions must work together to change existing maternity programs. 3. Plans for maternal and child health care in Aboriginal communities should include a "healing map" that outlines the determinants of health. 4. Midwifery care and midwifery training should be an integral part of changes in maternity care for rural and remote Aboriginal communities. 5. Protocols for emergency and non emergency clinical care in Aboriginal communities should be developed in conjunction with midwifery programs in those communities. 6. Midwives working in rural and remote communities should be seen as primary caregivers for all pregnant women in the community. PMID- 17346498 TI - Interferon alpha (pegylated and non-pegylated) and ribavirin for the treatment of mild chronic hepatitis C: a systematic review and economic evaluation. AB - OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of pegylated interferon alpha (PEG) and non-pegylated interferon alpha (IFN) and ribavirin (RBV) for the treatment of adults with histologically mild chronic hepatitis C (HCV) infection. DATA SOURCES: Electronic bibliographic databases were searched up to July 2005. REVIEW METHODS: A systematic review and an economic evaluation were carried out. A Markov state transition model was developed to estimate the cost-effectiveness of treatment strategies for adults with mild chronic HCV. RESULTS: Among the included studies, eight randomised controlled trials (RCTs) of antiviral treatment in mild HCV were identified and included. In general these RCTs were of good quality. The results suggested that effectiveness, particularly with respect to sustained virological response was similar in patients with mild disease to the results obtained in patients with moderate/severe disease. This finding was supported by RCTs reporting the results for mild HCV sub-groups. The authors' cost-effectiveness analysis showed that early treatment compared with watchful waiting is associated with quality adjusted life-year (QALY) gains but with increased treatment costs. The base-case incremental costs per QALY for 48 weeks of treatment are: watchful waiting with IFN + RBV versus best supportive care = pound 3097-6585; early treatment with IFN + RBV versus watchful waiting with IFN + RBV = pound 5043-8092; watchful waiting with PEG 2a + RBV versus best supportive care = pound 3052; early treatment with PEG 2a + RBV versus watchful waiting with PEG 2a + RBV = pound 5900; watchful waiting with PEG 2b + RBV versus best supportive care = pound 2534; and early treatment with PEG 2b + RBV versus watchful waiting with PEG 2b + RBV = pound 5774. These results were consistent with previous assessments of cost effectiveness. CONCLUSION: This systematic review and economic evaluation show that patients with histologically mild HCV can be successfully treated with both pegylated and non-pegylated interferon alpha. Early treatment and watchful waiting strategies are associated with acceptable cost-per-QALY estimates. Research needs to be directed towards newer, potentially more effective interventions, particularly those that improve treatment response in patients with genotype 1, with minimal adverse effects. Further research is required into the natural history of HCV to estimate better the rate of liver disease progression, and also into the effectiveness of non-invasive biochemical markers of liver disease, as an alternative to liver biopsy. PMID- 17346497 TI - Diagnosis and management of placenta previa. AB - OBJECTIVE: To review the use of transvaginal ultrasound for the diagnosis of placenta previa and recommend management based on accurate placental localization. OPTIONS: Transvaginal sonography (TVS) versus transabdominal sonography for the diagnosis of placenta previa; route of delivery,based on placenta edge to internal cervical os distance; in-patient versus out-patient antenatal care; cerclage to prevent bleeding; regional versus general anaesthesia; prenatal diagnosis of placenta accreta. OUTCOME: Proven clinical benefit in the use of TVS for diagnosing and planning management of placenta previa. EVIDENCE: MEDLINE search for "placenta previa" and bibliographic review. BENEFITS, HARMS, AND COSTS: Accurate diagnosis of placenta previa may reduce hospital stays and unnecessary interventions. RECOMMENDATIONS: 1. Transvaginal sonography, if available, may be used to investigate placental location at any time in pregnancy when the placenta is thought to be low-lying. It is significantly more accurate than transabdominal sonography, and its safety is well established. (11-2A) 2. Sonographers are encouraged to report the actual distance from the placental edge to the internal cervical os at TVS, using standard terminology of millimetres away from the os or millimetres of overlap. A placental edge exactly reaching the internal os is described as 0 mm. When the placental edge reaches or overlaps the internal os on TVS between 18 and 24 weeks' gestation (incidence 2-4%), a follow-up examination for placental location in the third trimester is recommended. Overlap of more than 15 mm is associated with an increased likelihood of placenta previa at term. (ll-2A) 3. When the placental edge lies between 20 mm away from the internal os and 20 mm of overlap after 26 weeks' gestation, ultrasound should be repeated at regular intervals depending on the gestational age, distance from the internal os, and clinical features such as bleeding, because continued change in placental location is likely. Overlap of 20 mm or more at any time in the third trimester is highly predictive of the need for Caesarean section (CS). (llI-B) 4. The os-placental edge distance on TVS after 35 weeks' gestation is valuable in planning route of delivery. When the placental edge lies > 20 mm away from the internal cervical os, women can be offered a trial of labour with a high expectation of success. A distance of 20 to 0 mm away from the os is associated with a higher CS rate, although vaginal delivery is still possible depending on the clinical circumstances. (ll-2A) 5. In general, any degree of overlap (> 0 mm) after 35 weeks is an indication for Caesarean section as the route of delivery. (ll-2A) 6. Outpatient management of placenta previa may be appropriate for stable women with home support, close proximity to a hospital, and readily available transportation and telephone communication. (ll-2C) 7. There is insufficient evidence to recommend the practice of cervical cerclage to reduce bleeding in placenta previa. (llI-D) 8. Regional anaesthesia may be employed for CS in the presence of placenta previa. (II-2B) 9. Women with a placenta previa and a prior CS are at high risk for placenta accreta. If there is imaging evidence of pathological adherence of the placenta, delivery should be planned in an appropriate setting with adequate resources. (II-2B) VALIDATION: Comparison with Placenta previa and placenta previa accreta: diagnosis and management. Royal College ofObstetricians and Gynaecologists, Guideline No. 27,October 2005.The level of evidence and quality of recommendations are described using the criteria and classifications of the Canadian Task Force on Preventive Health Care (Table). PMID- 17346499 TI - Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. AB - OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of bevacizumab and cetuximab in the treatment of individuals with metastatic colorectal cancer (CRC). DATA SOURCES: Searches of main electronic databases were conducted in April and May 2005. REVIEW METHODS: For the assessment of bevacizumab, trials were included if they recruited participants with untreated metastatic CRC for first-line treatment. Only trials comparing bevacizumab in combination with irinotecan and/or established fluorouracil (5-FU)-containing or releasing regimens given as first-line therapy were included. For the assessment of cetuximab, trials were included if they recruited participants with epidermal growth-factor receptor-expressing metastatic CRC who had previously failed irinotecan-including therapy. Independent cost-effectiveness models of bevacizumab and cetuximab were developed using survival modelling methods. RESULTS: Adding bevacizumab to irinotecan in combination with 5-FU/folic acid (FA) plus irinotecan resulted in a statistically significant increase in median overall survival (OS) of 4.7 months. Adding bevacizumab to 5-FU/FA resulted in a non-significant increase in median OS of 3.7 months within one study and 7.7 months in another. Adding bevacizumab to irinotecan, fluorouracil and leucovorin (IFL) resulted in a statistically significant increase in median progression-free survival (PFS) of 4.4 months. Adding bevacizumab to 5-FU/FA resulted in a statistically significant increase in median PFS of 3.7 months, and a statistically significant increase in time to disease progression of 3.8 months compared to FU/FA alone. An overall tumour response rate of 44.8% was reported for bevacizumab plus IFL compared to 34.8% for IFL plus placebo. This addition was statistically significant. The addition of bevacizumab to 5-FU/FA resulted in a significant difference in tumour response rate within one study, but not another. Bevacizumab in combination with IFL or 5-FU/FA was observed to result in an increase of grade 3/4 adverse events. The independent health economic assessment suggests that the cost-effectiveness of bevacizumab plus IFL is unlikely to be better than pound 46,853 per life-year gained (LYG); the cost utility of bevacizumab plus IFL is unlikely to be better than pound 62,857 per quality-adjusted life-year (QALY) gained. The cost-effectiveness of bevacizumab plus 5-FU/FA versus 5-FU/FA is unlikely to be better than pound 84,607 per LYG; the cost-utility of bevacizumab plus 5-FU/FA versus 5-FU/FA is unlikely to be better than pound 88,658 per QALY gained. A Phase II trial reported a median OS duration of 8.6 months for patients receiving cetuximab plus irinotecan, plus a median time to progression of 4.1 months, a tumour response rate of 22.9% and suggested that treatment with cetuximab in combination with irinotecan is associated with significantly more adverse events (any grade 3 or grade 4 adverse event) than cetuximab monotherapy. The single arm study of cetuximab plus irinotecan reported a median OS duration of 8.4 months, a median time to progression of 2.9 months and a tumour response rate of 15.2%. The cost effectiveness model suggested that the expected survival duration of patients receiving cetuximab plus irinotecan is 0.79 years (9.5 months) when the proposed continuation rule is applied. In order for cetuximab plus irinotecan to achieve a cost-utility ratio of pound 30,000 per QALY gained, treatment with cetuximab plus irinotecan must provide an additional 0.65 life years (7.8 months) over treatment with active/best supportive care, implying that survival in the active/best supportive care group must be 0.14 life years (1.7 months) or less. CONCLUSIONS: The trials indicate that bevacizumab in combination with 5-FU/FA, and bevacizumab in combination with IFL, is clinically effective in comparison to standard chemotherapy options for the first-line treatment of metastatic CRC. The health economic analysis suggests that the marginal cost-utility of bevacizumab plus IFL versus IFL is unlikely to be better than pound 62,857 per QALY gained, and the marginal cost-utility of bevacizumab plus 5-FU/FA versus 5-FU/FA is unlikely to be better than pound 88,658 per QALY gained. There is no direct evidence to demonstrate whether cetuximab in combination with irinotecan improves health related quality of life or OS in comparison to active/best supportive care or oxaliplatin plus 5-FU/FA, although the evidence on tumour response rates suggests that cetuximab plus irinotecan has some clinical activity. While it is difficult to suggest whether cetuximab represents value for money, indirect comparisons suggest that the incremental cost-utility of cetuximab plus irinotecan is unlikely to be better than pound 30,000 per QALY gained. This review highlights a number of areas for further research, including clarifying the true impact of first-line bevacizumab in combination with irinotecan and/or infusional 5-FU/FA, without subsequent bevacizumab treatment following disease progression, on OS in patients with metastatic CRC who are representative of the typical population of CRC patients in England and Wales. Further research concerning the impact of therapies on health-related quality of life is essential. PMID- 17346500 TI - Discussion: 'Accuracy of preoperative endometrial sampling' by Huang et al. PMID- 17346501 TI - Prospective risk of intrauterine death of monochorionic-diamniotic twins. PMID- 17346503 TI - Sulprostone reduces the need for manual removal of the placenta in patients with retained placenta: a randomized controlled trial. PMID- 17346505 TI - Risk factors of abruptio placentae among Peruvian women. PMID- 17346506 TI - Predicting uterine weight before hysterectomy: ultrasound measurements vs clinical assessment. PMID- 17346507 TI - Amniotic fluid volume and perinatal outcome. PMID- 17346508 TI - Should intravaginal slingplasty (IVS) procedure be abandoned? PMID- 17346509 TI - Posterior vaginal sling experience in elderly patients yields poor results. PMID- 17346511 TI - Proposal for translational and collaborative research model in Taiwan. PMID- 17346514 TI - Long-term complications with major impact on the quality of life in an aging population. PMID- 17346515 TI - Treatment of suspected fetal macrosomia: a cost-effectiveness analysis. PMID- 17346517 TI - Incarcerated vaginal herniation of the omentum mimicking vaginal prolapse. AB - We present a 33-year-old woman with a history of radical hysterectomy and pelvic radiation who developed a nonreducible high anterior vaginal wall bulge, postoperative pelvic pain, and dyspareunia. Dynamic MRI revealed herniation of the omentum into the vesico-vaginal space. The incarcerated hernia was repaired transvaginally, and the patient's symptoms improved. PMID- 17346518 TI - Plasma cell granuloma of urethra in a young woman. AB - This report describes an unfamiliar vulval mass that looked unidentifiable initially, but then was determined histologically to be urethral plasma cell granuloma. The lung is most commonly involved in plasma cell granuloma, and extrapulmonary lesions are considered uncommon. In particular, urethral plasma cell granuloma seems to be extremely rare. PMID- 17346520 TI - 17 Progesterone for preterm birth prevention: a potential 2 billion dollar opportunity. PMID- 17346521 TI - A thoughtful algorithm for the accurate diagnosis of primary CMV infection in pregnancy. PMID- 17346522 TI - Meta-analysis of first trimester Down syndrome screening studies: free beta-human chorionic gonadotropin significantly outperforms intact human chorionic gonadotropin in a multimarker protocol. AB - OBJECTIVE: The purpose of this study was to compare free beta and intact human chorionic gonadotropin in first trimester screening with pregnancy-associated plasma protein-A and nuchal translucency. STUDY DESIGN: A Monte Carlo simulation trial was conducted based on a literature review of the PUBMED database (1966 to November 2005). RESULTS: In younger patients (< 35 years), detection of Down syndrome increased by 4, 5, 6, and 7 percentage points when free beta was added to pregnancy-associated plasma protein-A and nuchal translucency compared with 0, 0, 2, and 4 percentage points for intact human chorionic gonadotropin at 9-12 weeks' gestation, respectively. In advanced maternal age patients (> or = 35), inclusion of free beta-human chorionic gonadotropin reduced the false-positive rate by 2.5, 3.1, 3.8, and 4.4 percentage points compared with 0.1, 0.3, 1.0, and 2.2 percentage points for intact human chorionic gonadotropin at 9-12 weeks, respectively. CONCLUSION: The results of our analysis suggest that in a first trimester Down syndrome screening protocol free beta-human chorionic gonadotropin achieves higher sensitivity and lower false-positive results than intact human chorionic gonadotropin . Moreover, intact human chorionic gonadotropin does not add substantially to screening performance until the end of the first trimester. PMID- 17346523 TI - Review of the economic and quality-of-life burden of cervical human papillomavirus disease. AB - OBJECTIVE: The purpose of this study was to conduct a systematic literature review on the economic burden and health-related quality-of-life impact of cervical human papillomavirus disease. STUDY DESIGN: A systematic review of cost of-illness studies and health-related quality-of-life studies was conducted. PubMed, Embase, and PsycINFO databases were searched with the use of predefined terms. RESULTS: Nine economic and 24 quality-of-life studies were identified. The annual health care costs of human papillomavirus-related conditions in the United States range from 2.25-4.6 billion dollars (2005 US dollars). The burden of human papillomavirus is second only to human immunodeficiency virus among sexually transmitted diseases. Health-related quality-of-life areas that are impacted substantially by human papillomavirus include emotional, social, and sexual functioning. CONCLUSION: The economic and quality-of-life burden of cervical human papillomavirus disease is significant and highlights the need for treatment and prevention options for this condition. PMID- 17346524 TI - Markers of muscle ischemia, necrosis, and inflammation following uterine artery embolization in the treatment of symptomatic uterine fibroids. AB - OBJECTIVE: The objective of the study was to quantify markers of myometrial ischemia, necrosis, and inflammation in women undergoing uterine artery embolization (UAE). STUDY DESIGN: Women with symptomatic fibroids were randomized to treatment with UAE (n = 14) or abdominal myomectomy (n = 11). Peripheral venous blood samples were taken before and after the procedure, at 24 hours and 6 weeks. Creatine kinase (CK) and ischemia-modified albumin (IMA) were measured as markers of necrosis and ischemia. Inflammation was assessed by measurement of C reactive protein (CRP). OUTCOME MEASURES: Changes in the markers following UAE and myomectomy were measured. RESULTS: Following UAE, no change was seen in CK or IMA, but CRP was raised only at 6 weeks. At 24 hours after myomectomy, there were significant rises in all 3 markers, with a return to normal by 6 weeks. CONCLUSION: No significant ischemia or necrosis occurs in the myometrium following UAE, whereas the delayed rise in CRP is likely to reflect necrosis in fibroids. PMID- 17346525 TI - Decreasing utilization of hysterectomy: a population-based study in Olmsted County, Minnesota, 1965-2002. AB - OBJECTIVE: The purpose of this study was to assess temporal trends for hysterectomy among Olmsted County, Minnesota women. STUDY DESIGN: Using the Rochester Epidemiology Project database, we identified all county residents undergoing a hysterectomy in 1965-2002. Temporal changes in the utilization (incidence) rate, type, diagnostic indications, and age at surgery were assessed. RESULTS: Between 1965 and 2002, 6152 women had a hysterectomy alone, whereas 3126 women had, in addition, a pelvic floor repair; the age-adjusted utilization rate for hysterectomy alone and for combined procedures declined (P < .0001) by 13% and 63%, respectively. Except for subjects aged 75-85 years, this decline affected every age group. The distribution of vaginal (56%) and abdominal (44%) procedures differed across indications. Uterine leiomyomata, precancerous conditions, and genital prolapse accounted for 28%, 23%, and 12% of all procedures, respectively. CONCLUSION: Among community women, the utilization rate, age distribution, and indications for a hysterectomy changed substantially between 1965 and 2002. PMID- 17346526 TI - Internal anal sphincter defect influences continence outcome following obstetric anal sphincter injury. AB - OBJECTIVE: To date, little correlation has been found between the extent of anal sphincter injury defined by endoanal ultrasound and symptoms of postpartum fecal incontinence. To define this relationship, we assessed a large cohort of women following first recognized obstetric anal sphincter injury. STUDY DESIGN: In all, 500 consecutive women were studied at 3 months following primary repair of a first recognized obstetric anal sphincter injury sustained during vaginal delivery. Assessment included a standardized fecal incontinence questionnaire (modified Jorge-Wexner score), anal manometry, and endoanal ultrasound. Severe fecal incontinence was defined by a score greater than 9. Statistical significance of the relationship between symptoms and factors including age, parity, mode of delivery, and extent of sphincter injury (defined by endoanal ultrasound), was analyzed through multiple logistic regression. RESULTS: Increasing age (P = .006) and parity (P = .039), instrumental delivery (P < .001), an anal canal resting pressure of < or = 35 mm Hg (P = .047), and internal anal sphincter (IAS) injury (P = .002) were significantly related to the presence of fecal incontinence. With multivariate analysis, and adjusting for other factors, instrumental delivery (OR 3.1; 95% CI 1.2-7.9) and IAS defect thickness (partial thickness defect > 1 quadrant or full thickness defect; OR 5.1 95% CI 1.5-22.9) were predictive of severe incontinence, but external anal sphincter defects were not. CONCLUSION: Endosonographic evidence of IAS injury is predictive of fecal incontinence following obstetric anal sphincter injury. The presence of an IAS defect should be sought carefully if the anal sphincter is injured during vaginal delivery. PMID- 17346527 TI - Medical cost savings associated with 17 alpha-hydroxyprogesterone caproate. AB - OBJECTIVE: This study was undertaken to assess the impact of 17 alpha hydroxyprogesterone caproate treatment on future medical costs for expectant mothers with a prior spontaneous preterm birth. STUDY DESIGN: Data on the costs of preterm birth were combined with published data on the effectiveness of 17 alpha hydroxyprogesterone caproate to produce estimates of the effect of treatment on expected future direct medical costs. These estimates were compared with an estimate of the cost of a typical 17 alpha hydroxyprogesterone caproate treatment regimen to estimate the net savings per treated woman. RESULTS: Treatment is estimated to reduce initial neonatal hospitalization costs by 3800 dollars per woman treated with 17 alpha hydroxyprogesterone caproate. Expected lifetime medical costs (discounted) of treated infants are estimated to decline 15,900 dollars. CONCLUSIONS: Treating expectant mothers with a prior spontaneous preterm birth with 17 alpha hydroxyprogesterone caproate generates future medical cost savings that substantially exceed the cost of treatment. If this population were universally treated with 17 alpha hydroxyprogesterone caproate, discounted lifetime medical costs of their offspring could be reduced by more than 2.0 billion dollars annually. PMID- 17346528 TI - Impact of diagnostic and confirmatory tests and prenatal counseling on the rate of pregnancy termination among women with positive cytomegalovirus immunoglobulin M antibody titers. AB - OBJECTIVE: The purpose of this study was to determine if diagnostic tests performed in a reference laboratory and the correct interpretation and communication of results by an expert physician to the patient can reduce the rate of unnecessary abortions among women with positive cytomegalovirus (CMV) immunoglobulin M antibody titers. STUDY DESIGN: This was a retrospective study of 1857 consecutive pregnant women with positive screening for IgM anti-CMV, in the first or second trimester of pregnancy, referred to our unit for further diagnostic evaluation. Patients with available follow-up were divided into 2 groups according to the results of confirmatory serologic testing: women with a CMV serologic profile suggestive of primary infection and hence at high risk of vertical transmission (group 1) and women with a CMV serologic profile consistent with nonprimary infection or past infection (group 2). The number of expected pregnancy terminations and the prevented fraction of abortions was calculated. RESULTS: Of 445 group 1 patients, 53 (11.9%) elected to terminate the pregnancy after being informed of the results of diagnostic tests; in contrast, only 5 (0.4%) women in group 2 underwent terminations (P < .001). At autopsy, 38 fetuses in group 1 proved infected. No information on fetal infection is available for pregnancies terminated in the first trimester (15 in group 1; 5 in group 2). We estimated that > or = 196 (11.9%) of all patients in groups 1 and 2 (n = 1650 patients) would have elected abortion on the basis of the positive result of screening for fetal CMV infection. After the results of confirmatory tests, only 58 women (53 in group 1 and 5 in group 2) elected to terminate the pregnancy. Thus, the number of abortions is presumed to have been decreased by 73% (P < .001). CONCLUSION: The correct interpretation and communication of confirmatory test results by expert physicians to pregnant women with positive screening for IgM anti-CMV may significantly reduce the rate of unnecessary abortions. PMID- 17346529 TI - Increased recurrence of preterm delivery with early cessation of 17-alpha hydroxyprogesterone caproate. AB - OBJECTIVE: The purpose of this study was to identify the effect of early cessation of 17-alpha-hydroxyprogesterone caproate (17P) on the incidence of spontaneous recurrent preterm delivery (PTD). STUDY DESIGN: Retrospective analysis of data from women who were enrolled for outpatient 17P administration between January 2004 and May 2006 included women with previous PTD and current singleton pregnancy who were beginning weekly 17P injections (250 mg intramuscularly) at 16-20.9 weeks. The study group was comprised of patients who were electively terminating 17P at <32.0 weeks and who delivered >10 days from the last injection. The control group consisted of patients who received weekly 17P injections until PTD or 36.9 weeks of gestation. The primary study outcome was the rate of recurrent spontaneous PTD. RESULTS: Study group patients were significantly more likely to have spontaneous recurrent PTD at <37 weeks of gestation (48.1% vs 33.3%; P = .011), at <35 weeks of gestation (30.9% vs 14.0%; P < .001), and at <32 weeks of gestation (16.0% vs 7.0%; P = .020). CONCLUSION: Early cessation of 17P treatment is associated with an increased risk for spontaneous recurrent PTD. PMID- 17346530 TI - Impact of interconception antibiotics on the endometrial microbial flora. AB - OBJECTIVE: The purpose of this study was to evaluate the impact of an interconception antibiotic regimen on endometrial microbial flora and histologic type. STUDY DESIGN: This was a secondary analysis of a double-blind randomized placebo-controlled trial of prophylactic metronidazole plus azithromycin that was given to 241 women (antibiotics, 118 women; placebo, 123 women) with a previous preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histologic types were obtained at randomization and 2 weeks after treatment. The prevalence of either the new acquisition or the resolution of individual microbes, categories of microbes, and plasma cell endometritis were compared by chi-square or Fishers' exact tests. RESULTS: Overall, antibiotics were associated with lower acquisition and higher resolution of microbes. Of women without Gardnerella at baseline, 14% of the women who received antibiotics vs 34% of the women who received placebo had positive endometrial culture for the organism after treatment (P < .05); of those women with G. vaginalis at baseline, 57% of the women who received antibiotics vs 33% of the women who received placebo (P < .05) had a negative follow-up culture. Other gram-negative rods, especially aerobes in general, manifested similar patterns. The impact on anaerobes and plasma cell endometritis was not definitive, but there was a trend toward the increased resolution of the former (77% vs 55%) and reduced acquisition of the latter (28% vs 50%). CONCLUSION: The antibiotic regimen prevented the acquisition and promoted the resolution, but not the eradication, of gram-negative rods such as G. vaginalis and the aerobic subcategory. PMID- 17346531 TI - Chorioamnionitis and fetal response in stillbirth. AB - OBJECTIVE: The purpose of this study was to determine the incidence of chorioamnionitis and fetal inflammatory response in a stillborn cohort and the relationship of fetal response to spontaneous labor, unexplained antepartum death, and spontaneous preterm death. STUDY DESIGN: In a 15-year hospital cohort study, placental histopathologic evidence, labor onset, gestation, and cause of death classification data were analyzed. RESULTS: Of 459 stillbirths, 428 stillbirths were included. The incidence of chorioamnionitis was 36.9%, with higher rates evident in early and late gestation. A fetal inflammatory response was present in 13.3% and correlated with spontaneous labor and very early spontaneous preterm death. The absence of a fetal response was associated with unexplained antepartum death. CONCLUSION: The increased incidence of chorioamnionitis at extremes of gestation in stillbirth is novel and has important implications. The impact of a fetal response is gestation dependent and its absence is associated with unexplained antepartum death. PMID- 17346532 TI - Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. AB - OBJECTIVE: This study was undertaken to determine the long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome treated with laser. STUDY DESIGN: All twin-to-twin transfusion syndrome cases treated at our center with laser between August 2000 and December 2003 were included in the study. Neurologic, mental, and psychomotor development at 2 years of age corrected for prematurity was assessed in all twin-to-twin transfusion syndrome survivors. Neurodevelopmental impairment was defined as any of the following: cerebral palsy, deafness, blindness, mental, or psychomotor development index of the Bayley Scales of Infant Development II less than 2 SD. RESULTS: A total of 82 twin-to-twin transfusion syndrome pregnancies were treated with fetoscopic laser surgery during the study period. Perinatal survival was 70% (115/164). The incidence of neurodevelopmental impairment was 17% (19/115) and was due to cerebral palsy (n = 8), mental developmental delay (n = 9), psychomotor developmental delay (n = 12), and deafness (n = 1). CONCLUSION: The incidence of neurodevelopmental impairment in twin-to-twin transfusion syndrome survivors treated with laser is high and warrants long-term follow-up. PMID- 17346533 TI - Concordance of chart abstraction and patient recall of intrapartum variables up to 53 years later. AB - OBJECTIVE: The purpose of this study was to determine the concordance of patient recall compared with chart abstraction for distant intrapartum variables and to evaluate predictors of concordance. STUDY DESIGN: A random sample from a cohort of diverse women aged 40-74 years. Intrapartum variables reported by participants were compared with the medical record. Outcomes were assessed for sensitivity, specificity, positive predictive value, and negative predictive value. Multivariate logistic regression was used to determine predictors of concordance of patient recall. RESULTS: Four hundred one births among 178 women were analyzed. Recall of cesarean delivery had the highest concordance (sensitivity, 0.98; specificity, 1.00; positive predictive value, 1.00; negative predictive value, 0.99). Laceration that required repair had the lowest concordance (sensitivity, 0.37; specificity, 0.68; positive predictive value, 0.34; negative predictive value, 0.81). No variables predicted concordance of recall for all variables. CONCLUSION: The concordance of patient recall to chart abstraction for intrapartum variables varies widely, although with a pattern of greater specificity and negative predictive value of recall. This should be kept in mind during patient interviews and in the performance of clinical research. PMID- 17346534 TI - Modelflow: a new method for noninvasive assessment of cardiac output in pregnant women. AB - OBJECTIVE: Estimation of cardiac output by continuous finger arterial pressure waveform analysis with Modelflow is a noninvasive technique for beat-to-beat hemodynamic assessment. The purpose of this study was to compare this method in pregnant women with the more commonly used Doppler echocardiography. STUDY DESIGN: In 16 primigravid women, stroke volume was measured serially in first, second, and third trimester and after pregnancy by the Modelflow method and by Doppler echocardiography. Aortic diameter and compliance were assessed serially by echocardiography and pulse wave velocity measurements. RESULTS: Aortic compliance was increased significantly in pregnancy compared with nonpregnant values, but aortic diameter did not change. After adjustment for pregnancy related changes in pulse wave velocity, blood pressure, and heart rate, Modelflow stroke volume measurements gave comparable results to Doppler echocardiography during and after pregnancy. The observed variation was similar to reported comparisons of Doppler echocardiography with thermodilution. CONCLUSION: After adjustment for pregnancy the Modelflow method is a useful research tool for assessment of stroke volume in pregnant women and offers the advantage of continuous measurement and convenience of application. PMID- 17346535 TI - Are perinatal and maternal outcomes different during expectant management of severe preeclampsia in the presence of intrauterine growth restriction? AB - OBJECTIVE: The purpose of this study was to compare perinatal and maternal outcomes in women with singleton pregnancies and severe preeclampsia (SPE) expectantly managed at 24-33 weeks' gestation (wk) that resulted at birth in severe intrauterine growth restriction (SIUGR, < 5th percentile) to those without SIUGR. STUDY DESIGN: Two hundred thirty-nine women undelivered after antenatal steroids were expectantly managed. Perinatal and maternal outcomes were analyzed according to fetal growth status. Students t-test, chi-square test, logistic regression analysis, and odds ratio were calculated. RESULTS: Fifty-eight pregnancies resulted in an SIUGR neonate. Median latency periods (5 vs 5 d) and delivery gestational ages (30.6 vs 30.3 wk) were similar in the 2 groups. Controlling for gestational age at delivery, only fetal death remained associated with SIUGR (OR: 6.4; 95% CI 1.05-39.35, P = .04). Maternal outcomes were similar in the 2 groups. CONCLUSION: In severe preeclamptic women at 24-33 weeks, SIUGR is associated with increased risk of fetal death but does not affect maternal complications. PMID- 17346536 TI - Changes in circulating level of angiogenic factors from the first to second trimester as predictors of preeclampsia. AB - OBJECTIVE: This study was undertaken to assess changes in placenta growth factor and soluble fms-like tyrosine kinase-1 as predictors of preeclampsia. STUDY DESIGN: Nested case-control study of 154 preeclampsia cases delivered preterm and 190 delivered at term, and 392 controls. RESULTS: Comparing the lowest and highest quartile of placenta growth factor increase from first to second trimester, the odds for preterm preeclampsia was 13.8 (95% CI, 4.4-43.2) higher for women with the lowest increase. Compared with controls, women with preterm preeclampsia had lower soluble fms-like tyrosine kinase-1 in the first, but higher in second trimester. Comparing highest and lowest quartile of increase, the odds for preterm preeclampsia was 9.2 (95% CI 3.4-25.0) higher for women with highest increase. Low placenta growth factor and high soluble fms-like tyrosine kinase-1 increase combined yielded extremely high relative risk of preterm preeclampsia (odds ratio, 35.3, 95% CI, 7.6-164.2), compared with the combination of high (placenta growth factor) and low (soluble fms-like tyrosine kinase-1) increase. CONCLUSION: Low placenta growth factor and high soluble fms-like tyrosine kinase-1 increase from first to second trimester are strong predictors of preeclampsia. PMID- 17346537 TI - Risk for postterm delivery after previous postterm delivery. AB - OBJECTIVE: We examined the hypothesis that the risk for subsequent postterm birth is increased in women with an initial postterm birth. STUDY DESIGN: We performed a population-based cohort study of Missouri births (1989-1997) to assess the recurrence of postterm birth using the Missouri Department of Health's maternally linked database. RESULTS: A total of 368,633 births were evaluated, of which 7.6% were postterm (>42 weeks of gestation). Black mothers had a lower risk for all (adjusted odds ratio [OR], 0.70; 95% CI, 0.67-0.73) or recurrent (adjusted OR, 0.73; 95% CI, 0.67-0.79) postterm birth. Maternal education of <12 years (adjusted OR, 1.51; 95% CI, 1.41-1.62), indices of low socioeconomic status, and maternal body mass index >35 kg/m2 (adjusted OR, 1.23; 95% CI, 1.11-1.37) were associated with increased risk for recurrent postterm birth. Mothers with an initial postterm birth were at increased risk for postterm birth (OR, 1.88; 95% CI, 1.79-1.97) in subsequent pregnancies, independent of race. CONCLUSION: Among mothers who deliver postterm, there is a significant risk for subsequent postterm births. This increased risk suggests that common factors (genetic or other) influence the likelihood of abnormal parturition timing. PMID- 17346538 TI - Accuracy of preoperative endometrial sampling for the detection of high-grade endometrial tumors. AB - OBJECTIVE: This study was undertaken to evaluate the ability of preoperative endometrial sampling to accurately diagnose high-grade endometrial tumors. STUDY DESIGN: Three hundred sixty endometrial cancer patients had preoperative endometrial sampling and hysterectomy specimens that underwent pathologic review at a single institution from 1995 to 2005. The sensitivity of Pipelle and curettage to diagnose high-grade endometrial tumors (grade 3 endometrioid adenocarcinoma, serous carcinoma, carcinosarcoma, clear cell carcinoma) was determined. Agreement between preoperative and hysterectomy diagnoses was measured by the Kappa statistic. RESULTS: Sensitivity of Pipelle and curettage was 93.8% and 97% in patients with low-grade cancer and 99.2% and 100% in patients with high-grade cancer. Good agreement was observed between the preoperative and the hysterectomy histologic diagnoses (Kappa = 0.69), and between the preoperative and hysterectomy tumor grade (Kappa=0.78). CONCLUSION: Preoperative endometrial sampling with Pipelle or curettage is sensitive and accurate for the diagnosis of high-grade endometrial tumors, including tumors with nonendometrioid histology. PMID- 17346539 TI - Gene expression profile of ovarian serous papillary carcinomas: identification of metastasis-associated genes. AB - OBJECTIVE: The purpose of this study was to identify genes that are highly differentially expressed in metastatic serous papillary ovarian tumors (MET) when compared with primary ovarian serous carcinomas (OSPC). STUDY DESIGN: An oligonucleotide microarray with probe sets complementary to >14,500 human genes was used to determine whether patterns of gene expression may differentiate OSPC from MET in 31 snap-frozen serous papillary ovarian carcinomas (ie, 14 primary OSPC and 17 omental metastasis [MET]). RESULTS: Hierarchic cluster analysis of gene expression in OSPC and MET identified 156 genes that exhibited > 2-fold differences (P < .05) and that distinguished OSPC from MET. A number of invasion and metastasis predictive genes (including plasminogen activator; matrix metalloproteinase; matrix structural constituent genes encoding products with collagen, heparin, and hyaluronic acid binding activity; genes encoding receptors for insulin-like growth factors; vascular endothelial growth factor; endothelin type A; fibroblast growth factor; thrombospondin 1 and 2; type A and B integrins, and chemokines [stromal cell-derived factor 1 (CXCL12)]) were found among the 120 genes that were highly differentially overexpressed in MET, when compared with OSPC. Down-regulated genes in MET compared with OSPC included hepsin and testisin. Overexpression of CXCL12, matrix metalloproteinase, plasminogen activator, type A and B integrins, and hepsin genes was validated by quantitative real-time polymerase chain reaction in all samples. Finally, overexpression of CXCL12 in MET, when compared with OSPC, was validated at the protein level by immunohistochemistry. CONCLUSION: Gene expression profiling may differentiate metastatic ovarian cancer from primary OSPC. The identification of metastasis associated genes may provide a foundation for the development of new type specific diagnostic strategies and treatment for metastatic ovarian cancer. PMID- 17346540 TI - Reduced progression of endometrial hyperplasia with oral mTOR inhibition in the Pten heterozygote murine model. AB - OBJECTIVE: Phosphatase and tensin homolog (PTEN) mutations are associated with human endometrial cancers, and PTEN heterozygote(+/-) mice have a high rate of endometrial neoplasia. The objective of this study was to evaluate an oral mTOR inhibitor (mTOR-I) on the reduction of endometrial hyperplasia in an animal model. STUDY DESIGN: Three groups of 10 female mice were treated from age 20-26 weeks: group A, Pten wild type with mTOR-I; group B, Pten+/- with placebo; and group C, Pten +/- with mTOR-I. Rates of hyperplasia and markers of proliferation and apoptosis were evaluated. RESULTS: Higher grade hyperplasia occurred in a significantly greater percentage of the untreated Pten+/- group B (80%; 8/10) compared with groups A (0%; 0/10) and C (20%; 2/10; P < .02). The treated Pten+/- mTOR-I group C also demonstrated significantly increased apoptosis (P < .002) and decreased proliferation index (P < .02) compared with the untreated group B. CONCLUSION: Oral mTOR inhibition decreases the progression of endometrial hyperplasia in the Pten heterozygote murine model through decreased cell proliferation and increased apoptosis. PMID- 17346541 TI - Laparoscopy-assisted vaginal hysterectomy compared with abdominal hysterectomy in clinical stage I endometrial cancer: safety, recurrence, and long-term outcome. AB - OBJECTIVE: To determine the feasibility of laparoscopic-assisted vaginal hysterectomy (LAVH) in the treatment of clinical FIGO stage I endometrial adenocarcinoma and long-term survival outcome. STUDY DESIGN: Prospective cohort study without randomization of 169 consecutive patients. Laparoscopy or laparotomy was selected based on size and mobility of the uterus and Body Mass Index (BMI). Lymphadenectomy was only performed in cases at high-risk for nodal metastases. RESULTS: Sixty-nine patients (41%) treated successfully by LAVH (LAVH group) while 100 (59%) by total abdominal hysterectomy (TAH) (laparotomy group). Four out of 73 patients initially approached by laparoscopy were converted to laparotomy (5.5%). Lymphadenectomy was performed in 40% of the LAVH and 57% of TAH group (P = 0.03). The median number of pelvic lymph nodes removed by LAVH and laparotomy was 15 (range 2-31) and 21 (range 2-65), respectively (P = 0.05). LAVH was associated with more surgical FIGO stage IA disease and a smaller tumor diameter. Operative time was significantly longer with laparoscopy compared with laparotomy, while blood loss and duration of hospitalization was significantly lower in the LAVH group. The recurrence rate in the LAVH group was 8.7%, compared with 16% in the laparotomy group (not significant, NS). The actuarial overall survival (OS) and disease-free survival (DFS) for the LAVH were 93% and 91% compared with 86% and 84% in the TAH, respectively (NS). In the multivariate analyses histological subtype was the only independent prognostic factor for DFS, while surgical technique was not. CONCLUSION: LAVH with lymphadenectomy in selected population in high-risk patients with clinical stage I endometrial adenocarcinoma and with favorable body mass index of less than 35 kg/m2, appears to be safe procedure. PMID- 17346542 TI - Origin and insertion points involved in levator ani muscle defects. AB - OBJECTIVE: This project sought to identify and to describe the anatomical connections affected by levator ani defects involving the pubovisceral portion of the muscle. STUDY DESIGN: Fourteen magnetic resonance scans of women with unilateral levator defects were selected. The missing muscle mapping technique was used to characterize the absent muscle. Normal muscle was visualized and compared with the contralateral side. Using a three-dimensional slicer, the outline of the intact muscle was traced; models of this muscle and surrounding structures were generated. RESULTS: The missing muscle originates from the posterior pubic bone and extends laterally over the obturator internus muscle; it inserts into the vaginal wall, perineal body, and the intersphincteric space. Architectural distortion, with an asymmetric lateral spilling of the vagina was present in 50% of women. The defect was right sided in 71% of patients. CONCLUSION: The origin and insertion points of the damaged portion of the levator ani muscle were identified. PMID- 17346543 TI - Fetal aortic stenosis and changes in amniotic fluid natriuretic peptides. AB - OBJECTIVE: Natriuretic peptides, especially brain natriuretic peptide (BNP), have demonstrated great usefulness in pediatric and adult cardiology. We studied their usefulness, based on amniotic fluid concentrations, in an ovine model of fetal aortic stenosis and in response to fetal cardiac intervention. STUDY DESIGN: After their natural history was established with gestation (n = 18 fetuses), natriuretic peptide levels were measured in a fetal model of aortic stenosis (50 60 days; term, 148 days; n = 9) and were correlated to the severity of fetal heart disease. Response to fetal cardiac intervention in 3 hydropic fetuses was also assessed. Significance was established with 2-sided paired t-tests at a probability value of <.05. RESULTS: Amniotic fluid BNP (but not atrial natriuretic peptide) concentrations were elevated significantly with aortic stenosis (181.9 +/- 109.9 pg/mL vs 50.0 +/- 40.5 pg/mL in control fetuses), especially if complicated with hydrops (283 +/- 74.4 pg/mL), and were correlated positively with the severity of stenosis and left ventricle hypertrophy. In the 1 animal surviving fetal intervention, BNP levels normalized. CONCLUSION: Amniotic fluid BNP concentrations correlate with the severity of fetal aortic stenosis. PMID- 17346544 TI - Natural antimicrobial production by the amnion. AB - OBJECTIVE: The purpose of this study was to determine the expression of natural antimicrobials in primary cultured amnion epithelial cells and to examine their regulation by interleukin-1 beta (IL-1beta). STUDY DESIGN: Primary amnion epithelial cells were cultured from samples that were obtained at prelabor cesarean section (n = 12) and stimulated with IL-1beta. Natural antimicrobial messenger RNA expression was determined by real-time quantitative polymerase chain reaction, and protein was measured by enzyme-linked immunosorbent assay. Data was analyzed by analysis of variance. RESULTS: Primary amnion epithelial cells express messenger RNA for human beta defensin (HBD) 1 to 3, secretory leukocyte protease inhibitor and elafin, but not HBD4. IL-1beta 10 ng/mL stimulates HBD2 messenger RNA in a biphasic pattern, with a 51-fold increase at 6 hours and a 67-fold at 12 hours (P < .001). HBD2 protein production is significantly increased by 24 hours (P < .05). CONCLUSION: The amnion produces potent natural antimicrobials that may help protect the pregnancy from infection. HBD2 production is dramatically upregulated by the labor-associated inflammatory cytokine IL-1beta. PMID- 17346545 TI - Progesterone protects fetal chorion and maternal decidua cells from calcium induced death. AB - OBJECTIVE: The purpose of this study was to determine whether progesterone exerts a protective effect in chorion and decidua cells when exposed to calcimycin. STUDY DESIGN: Fetal membrane samples were collected from term elective repeat cesarean deliveries and chorion and decidua cells that are separated and cultured. Cells were pretreated with progesterone and exposed to calcimycin. Cell viability was determined, and percent cell viability was calculated. RESULTS: Exposure to calcimycin resulted in a reduction of cell viability in both chorion and decidua cells in a dose-dependent fashion. In chorion and decidua cells, progesterone pretreatment followed by calcimycin increased cell viability compared with calcimycin treatment alone (chorion, 67%, vs controls, 24%; P < .001; decidua, 58%, vs controls, 35%; P < .001). The progesterone receptor antagonist, RTI 6413-49a, blocked the protective effect of progesterone in both chorion and decidua cells. CONCLUSION: These preliminary results suggest that progesterone may provide a protective effect in fetal membrane cells and that this effect may be mediated through the progesterone receptor. PMID- 17346546 TI - Neuroprotective peptides prevent some alcohol-induced alteration in gamma aminobutyric acid A-beta3, which plays a role in cleft lip and palate and learning in fetal alcohol syndrome. AB - OBJECTIVE: Prenatal alcohol exposure affects 1 in 100 births in the United States and results in craniofacial dysmorphologic condition and learning disabilities. In a model for fetal alcohol syndrome, neuroprotective peptides prevented fetal death and learning deficits. The gamma-aminobutyric acid A (GABA) receptor subunit GABAbeta3 plays a critical role for nervous system and palate development. Our objective was to determine whether the neuropeptides prevented alcohol-induced damage through GABAbeta3. STUDY DESIGN: With a model for fetal alcohol syndrome, timed pregnant C57B16/J mice were treated on gestational day 8 with alcohol (25% alcohol) or control (saline solution) or alcohol plus peptides NAPVSIPQ + SALLRSIPA (NAP + SAL; 20 microg). Embryos were harvested at 6 and 24 hours and 10 days after treatment. Adult males were tested for learning on the Morris water maze, and their brains were dissected. With samples from at least 3 litters per time point, calibrator-normalized relative real-time polymerase chain reaction was performed for GABAbeta3 with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistical analysis included analysis of variance and Fisher protected least significant difference. RESULTS: Twenty-four hours and 10 days after treatment, alcohol decreased GABAbeta3 in the embryos (P < or = .01); this decrease was prevented by the peptides (P = .01). GABAbeta3 was higher in alcohol treated adult brains respect to the controls (P = .002); this rise was not prevented by the peptides. CONCLUSION: Treatment with the neuropeptides NAPVSIPQ and SALLRSIPA prevented the alcohol-induced decline in GABAbeta3 expression 10 days after alcohol exposure. Because palate formation continues through E18, NAPVSIPQ and SALLRSIPA may be beneficial for the prevention of cleft lip and palate. PMID- 17346547 TI - Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. AB - OBJECTIVE: Preeclampsia and small-for-gestational age (SGA) neonates have partially overlapping clinicopathologic features. MicroRNAs (miRNAs) are critical posttranscriptional regulators of gene expression. This study was performed to determine whether preeclampsia and SGA are associated with alterations in placental miRNA expression. STUDY DESIGN: Placentas were obtained from patients with (1) preeclampsia (n = 9); (2) SGA (n = 9); (3) preeclampsia + SGA (n = 9); and (4) a control group with spontaneous preterm labor and delivery (PTL; n = 9). The expression of 157 miRNAs was assessed by real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Differential expression between preeclampsia and the control group (miR-210, miR-182) and between preeclampsia + SGA and the control group (miR-210, miR-182*, and others) was found. Gene Ontology analysis of the target genes revealed enrichment for specific biological process categories (antiapoptosis: miR-182; regulation of transcription: miR 210). CONCLUSION: This study reports, for the first time, increased expression of specific placental miRNAs in preeclampsia with and without SGA. The findings also provide novel targets for further investigation of the pathophysiology of preeclampsia. PMID- 17346549 TI - Evidence for multiple circulating factors in preeclampsia. AB - OBJECTIVE: The purpose of this study was to enrich vasoactive factors that are present in the plasma of women with preeclampsia by the application of sequential fractionation and determination of the activity of each fraction in a bioassay. STUDY DESIGN: Pooled plasma from women with preeclampsia (n = 23) and matched control subjects (n = 23) was subjected to fractionation with ultrafiltration, targeted immunodepletion, or size exclusion chromatography. Myometrial arteries that were isolated from healthy cesarean section biopsy specimens (n = 28) were incubated with plasma fractions (2%, volume/volume), and their endothelial function was assessed by wire myography. RESULTS: Incubation of arteries with preeclampsia plasma or immunodepleted preeclampsia plasma had a deleterious effect on endothelial-dependent relaxation. Bioactivity of the plasma factors was absent in all fractions after either plasma ultrafiltration or separation with the use of size exclusion chromatography; however, activity was restored after recombination of these fractions. CONCLUSION: This study provides the first conclusive evidence that multiple synergistic factors, with a combined vasoactive effect, are present in the plasma of women with preeclampsia. PMID- 17346548 TI - Enhancing sealing of fetal membrane defects using tissue engineered native amniotic scaffolds in the rabbit model. AB - OBJECTIVE: The purpose of this study was to compare the efficacy of native engineered amniotic scaffolds (AS) and polyesterurethane scaffolds (DegraPol) and document wound healing response when sealing iatrogenic fetal membrane defects in the rabbit model. STUDY DESIGN: Native AS were engineered from freshly harvested membranes of 23 days' gestational age (GA; term = 31-2 d). Acellularity of AS was assessed by histology, light and scanning electron microscopy. Fetal membrane defects were created by 14 gauge-needle puncture at GA 23 days and primarily closed with AS (n = 10) or DegraPol (n = 10) or left unclosed (positive controls; n = 10). Sixty-one sacs served as negative controls. At GA 30 days a second look hysterotomy was performed to assess presence of amniotic fluid (AF) and harvest plugging sites for microscopic evaluation. RESULTS: Engineered AS had a cell-free collagenous fiber network. AF was significantly higher only in the DegraPol group (78%; P < .05) compared to the AF in positive controls (17%). Integration of plugs in the fetal membrane defect was better with AS than DegraPol, with higher reepithelialization rates (AS: 52.5% +/- 6.5%; DegraPol: 11.6% +/- 2.6%; P < .001) and proliferation indices (AS: 0.47 +/- 0.03; DegraPol: 0.28 +/- 0.04; P = .001). In both treatment groups, cell proliferation in the myometrium was increased (P < .05). CONCLUSION: Native AS seal iatrogenic fetal membrane defects better than DegraPol. Within a week, there is abundant reepithelilization and minimal local inflammation. This yields the proof of principle that engineered native, amniotic membrane scaffolds enhance fetal membrane wound healing response. PMID- 17346550 TI - Thrombin regulates monocyte chemoattractant protein-1 expression in human first trimester and term decidual cells. AB - OBJECTIVE: Excess decidual macrophage infiltration has been linked to preeclampsia and a failure of endovascular trophoblast invasion. Severe preeclampsia with shallow placentation has also been linked to acquired and inherited maternal thrombophilias and recurrent decidual hemorrhage, which generates thrombin from decidual cell-expressed tissue factor. Therefore, the current study evaluated whether thrombin affects monocyte chemoattractant protein 1 (MCP-1) expression in stromal cells that are derived from cycling and gestational endometrium. STUDY DESIGN: Stromal cells that are isolated from cycling endometrium and first trimester and term decidua were grown to confluence, treated for 7 days with 10(-8) mol/L estradiol (E2) + 10(-7) mol/L medroxyprogesterone acetate (MPA), then switched to a serum-free medium that contained the corresponding steroids +/- thrombin. MCP-1 protein release was measured by enzyme-linked immunosorbent assay and Western blot; MCP-1 messenger RNA levels were assessed by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: Secreted MCP-1 levels were not significantly different in stromal or decidual cell cultures that were incubated with E2 or with E2 + MPA. Thrombin increased immunoreactive MCP-1 expression in a dose response fashion in first trimester and term decidual cells but not in endometrial stromal cells. Thrombin-induced MCP-1 protein output was unaffected by MPA but was abrogated by incubation with the thrombin inhibitor, hirudin. Unexpectedly, thrombin-enhanced MCP-1 protein expression was unaccompanied by corresponding changes in steady state MCP-1 messenger RNA levels, which suggests its effects were posttranslational. CONCLUSION: MCP-1 protein expression is up regulated by thrombin in decidual cells across gestation, but not in stromal cells from predecidualized cycling endometrium. PMID- 17346551 TI - Frontomaxillary facial angle in fetuses with trisomy 21 at 11-13(6) weeks. AB - OBJECTIVE: The objective of the study was to investigate the location of the front of the maxilla in relation to the forehead in fetuses with trisomy 21 at 11 13 weeks of gestation. STUDY DESIGN: A three-dimensional volume of the fetal head was obtained before karyotyping in 100 fetuses with trisomy 21 and 300 euploid fetuses. The frontomaxillary facial (FMF) angle, defined as the angle between the upper surface of the upper palate and the frontal bone in a midsagittal view of the fetal face, was measured. RESULTS: The FMF angle was significantly larger in the trisomy 21 than in the euploid fetuses (mean 88.7 degrees, range 75.4-104 degrees vs mean 78.1 degrees, range 66.6-89.5 degrees, P < .001). The FMF angle was more than 85 degrees in 69% of the trisomy 21 fetuses and in 5% of the euploid fetuses. There was no significant association between the FMF angle and nuchal translucency thickness. CONCLUSION: Measurement of FMF angle is likely to be a useful adjunct in screening for trisomy 21. PMID- 17346552 TI - Quality control of an image-scoring method for nuchal translucency ultrasonography. AB - OBJECTIVE: The objective of the study was to describe a new image-scoring method (NISM) for the measurement of nuchal translucency and crown-rump length on ultrasound scans and to establish interreviewer reliability. STUDY DESIGN: This NISM was based on 8 criteria on a scale of 4 levels (1-4) established on clearly defined ultrasound reference marks. Ten reviewers assessed the same images of 30 fetuses. After a short training period, the same images and those of 30 new fetuses were scored by these 10 reviewers. RESULTS: The differences in scores among the 10 reviewers were significant for 4 of 45 pairwise comparisons before training, but no pairwise comparison was significant after training. Interreviewer variance was significantly lower after training (P = .045). The intraclass correlations before and after training were 0.75 and 0.82. For each criterion, the scores were dichotomized into 2 categories (1-2 vs 3-4). Kappa values for each criterion were substantial (0.61 to 0.80) or even almost perfect (0.81 to 1.00). CONCLUSION: This NISM was highly reliable for the total scores and for each criterion evaluating the image of nuchal translucency and crown-rump length and provides a relevant quality control tool for ultrasound operators. PMID- 17346553 TI - Have predictors of obstetrics and gynecology career choice among contemporary US medical graduates changed over time? AB - OBJECTIVE: We sought to identify predictors of obstetrics and gynecology (OBGYN) specialty choice among US medical graduates over time. STUDY DESIGN: We examined OBGYN specialty choice for its association with 16 items on the 1997, 2000, and 2004 AAMC Graduation Questionnaire (GQ). Multivariate logistic regression identified independent predictors of OBGYN specialty choice for each year. RESULTS: Eighty-three percent of US graduates completed the GQ in the 3 years studied. Fewer responders chose OBGYN over time (1997, 8.2%; 2000, 6.5%; 2004, 6.2%). Women, blacks, and graduates with more positive ratings of the OBGYN clerkship were more likely to choose OBGYN in each year (each P < .001). Graduates reporting more positive beliefs about the practice of medicine and preferring academic careers were less likely to choose OBGYN (each P < .05). CONCLUSION: Predictors of OBGYN specialty choice from among the GQ variables tested have remained stable over time, but with a smaller pool of likely applicants. PMID- 17346554 TI - Clinical first-trimester routine screening for Down syndrome in singleton pregnancies in northern Finland. AB - OBJECTIVE: The purpose of this study was to compare the efficacy of both separate and combined maternal serum testing and fetal nuchal translucency measurement in the first trimester screening for Down syndrome in northern Finland. STUDY DESIGN: The following screening tests were evaluated: measurement of nuchal translucency (NT) alone; serum screening (pregnancy-associated plasma protein A [PAPP-A] and free beta subunit of human chorionic gonadotropin [beta-hCG]) alone; and combined screening (NT plus PAPP-A and free beta-hCG). RESULTS: The participants comprised 7534 pregnant women during the 10+0-12+6 weeks of pregnancy. All 7534 women participated in serum screening, and 4765 women participated in combined screening. In the serum screening-alone group, there were 30 cases of trisomy 21, of which 23 (76%) were detected. In the combined screening group, there were 24 cases of trisomy 21 and 21 (87.5%) were detected. In the combined-screening group NT alone detected 15 cases of Down syndrome (62%). CONCLUSION: Combined screening is the method of choice for Down syndrome screening. PMID- 17346555 TI - How accurate is Pipelle sampling: a study by Huang et al. PMID- 17346556 TI - An emerging diagnosis. PMID- 17346558 TI - An approach to congenital malformations of the head and neck. AB - It is easy to be overwhelmed when faced with the hundreds of cataloged anomalies of the head and neck region. For any individual defect there may be variation in phenotype, associated anomalies, and cause. To help organize these various disorders, dysmorphologists have grouped them into "syndromes", "sequences" and "associations" based on our level of understanding of their etiologies. Recently, completion of the human genome project has added a new level of complexity to the study of human malformations by providing a flood of new information about the genetic origins of established syndromes. The article describes the dysmorphologist's approach to the child with one or more anomalies and provides a glimpse into the future of human genetics. PMID- 17346559 TI - Congenital malformations of the skull and meninges. AB - The surgery and management of children who have congenital malformations of the skull and meninges require multidisciplinary care and long-term follow-up by multiple specialists in birth defects. The high definition of three-dimensional CT and MRI allows precise surgery planning of reconstruction and management of associated malformations. The reconstruction of meningoencephaloceles and craniosynostosis are challenging procedures that transform the child's appearance. The embryology, clinical presentation, and surgical management of these malformations are reviewed. PMID- 17346560 TI - Cleft lip and palate. AB - Patients who have cleft lip or palate face significant lifelong communicative and aesthetic challenges and difficulties with deglutition. Management of patients who have orofacial clefting requires an understanding of the anatomy and pathophysiology associated with clefting and the developmental difficulties encountered by these patients. This article describes current surgical concepts and principles of cleft care. Advances in the embryology and genetics of orofacial clefting are also discussed. It is expected that the care of patients who have clefts will continue to evolve because of advances in the fields of tissue engineering, genetics, and fetal surgery. PMID- 17346561 TI - Microtia and congenital aural atresia. AB - Microtia and congenital aural atresia (CAA) are congenital anomalies that are so common that every otolaryngologist should be familiar with the initial evaluation and care of the patient. When one ear hears normally, speech and language development should be normal. The gross and fine motor development of the baby or child is not expected to be affected in isolated cases of microtia and CAA. Current technologies allow for reconstruction or habilitation of the microtic ear when the child is several years of age. The hope is that tissue engineering can eliminate donor site morbidity. Temporary prosthetic ears will remain an option. Aural atresia work continues to be very dependent on the patient anatomy and the need or desire for better hearing in the affected ear. PMID- 17346562 TI - Anomalies of the middle and inner ear. AB - The development of the middle and inner ear highlights the intricacy of embryology. As early as 3 weeks after fertilization, the inner ear begins taking form. This process, along with development of the middle ear, continues throughout gestation. At birth, the middle ear, inner ear, and associated structures are almost adult size. An understanding of the embryologic development of the ear serves as a foundation for evaluating and managing congenital malformations of these structures. The focus of this article is the normal, abnormal, and arrested development of the middle and inner ear, with a clinical emphasis on malformed middle and inner ear structures and a discussion of associated syndromes. PMID- 17346563 TI - Congenital nasal malformations. AB - The nose is a prominent feature of the human face. Congenital malformations of the nose, whether functional or anatomic, affect the physiologic and psychologic wellness of children who have these anomalies. Congenital nasal abnormalities may be overt or subtle and can occasionally cause life-threatening emergencies at birth. A discussion of nasal embryology and development provides the basis for the discussion of some of the important congenital abnormalities seen in clinical practice. The final portion of the article is devoted to several of the more common syndromes in which nasal abnormalities are encountered. PMID- 17346564 TI - Congenital malformations of the eye and orbit. AB - Congenital malformations may affect any part of the eye and the ocular adnexa. Developmental defects may occur in isolation or as part of a larger systemic malformation syndrome. Many malformations can severely impair vision, whereas others have only cosmetic significance, and still others cause no symptoms and may go undiscovered or may be noted incidentally on routine eye examination. Congenital anomalies have numerous causes, most commonly of developmental genetic origin. The genetic basis of congenital eye and orbit anomalies is just beginning to be delineated, and future research on the subject will undoubtedly broaden understanding of the developmental etiology, pathophysiology, and treatment of congenital ocular disorders. PMID- 17346565 TI - Congenital malformations of the oral cavity. AB - Congenital malformations of the oral cavity may involve the lips, jaws, hard palate, floor of mouth, and anterior two thirds of the tongue. These malformations may be the product of errors in embryogenesis or the result of intrauterine events disturbing embryonic and fetal growth. This article begins with a review of the pertinent embryologic development of these structures. After reviewing the normal embryology, specific malformations are described. Recommended management follows the brief description of each malformation. An attempt is made to point out where these malformations deviate from normal development. Finally, management recommendations are based on traditional methods and recent advances described in the literature. PMID- 17346566 TI - Congenital cervical cysts, sinuses and fistulae. AB - Congenital cervical anomalies are important to consider in the differential of head and neck masses in children and adults. These lesions can present as palpable cystic masses, infected masses, draining sinuses, or fistulae. Thyroglossal duct cysts are most common, followed by branchial cleft anomalies, dermoid cysts, and more rarely median cervical clefts. Other topics discussed include median ectopic thyroid, cervical teratomas, and branchiootorenal syndrome. Appropriate diagnosis and management of these lesions requires a complete understanding of their embryology and anatomy. Correct diagnosis, resolution of infectious issues before definitive therapy, and complete surgical excision are essential to prevent recurrence. PMID- 17346567 TI - Congenital anomalies of the larynx. AB - Congenital laryngeal anomalies are relatively rare. However, they may present with life-threatening respiratory problems in the newborn period. Associated problems with phonation and swallowing may prevent a baby from thriving. Stridor is the most common presenting symptom of congenital laryngeal abnormalities. Often, it is associated with dysphagia, aspiration, and failure to thrive. Endoscopy is essential for evaluation and diagnosis in most cases. The differential diagnosis includes laryngeal cysts, atresia and stenosis, vocal fold immobility, and subglottic hemangiomas. In this article, the authors discuss in detail the evaluation and treatment for each condition. PMID- 17346568 TI - Congenital tracheal anomalies. AB - Congenital tracheal lesions are rare, but important, causes of morbidity in infants and children. Consequently, experience in their management is limited and dispersed. Given its small diameter, the juvenile trachea is obstructed easily by various natural causes, or following a surgical intervention. The diagnosis of a congenital, tracheal, obstructive anomaly is based on a high degree of suspicion in infants and children with respiratory distress accompanied by retraction. In this article, the authors discuss the various causes of these conditions, their diagnostic features, and the treatment possibilities. PMID- 17346569 TI - Congenital anomalies of the esophagus. AB - Normal anatomy, embryology, and congenital anomalies of the esophagus are discussed in this article. The classification, epidemiology, embryology, diagnosis, and management, including outcome following repair of esophageal atresia with or without an associated tracheoesophageal fistula, are described. The diagnosis and management of less common anomalies, such as congenital esophageal stenosis and congenital esophageal duplication, are outlined. PMID- 17346571 TI - [Preprosthesis surgery: a case of oligodontia]. PMID- 17346574 TI - Where have all the teachers gone? PMID- 17346575 TI - Mini-implant for intrusion: is it always justified? PMID- 17346577 TI - Herbst appliance. PMID- 17346578 TI - Digital videographic measurement of tooth display and lip position in smiling and speech: reliability and clinical application. AB - INTRODUCTION: Tooth display and lip position in smiling and speech are important esthetic aspects in orthodontics and dentofacial surgery. The spontaneous smile and speech are considered valuable diagnostic criteria in addition to the posed social smile. A method was developed to measure tooth display in both smile types and speech. METHODS: The faces of 20 subjects were individually filmed. Spontaneous smiles were elicited by a comical movie. The dynamics of the spontaneous smile were captured twice with a digital video camera, transferred to a computer, and analyzed on videoframe level. Two raters were involved. Posed social smiles and speech records were also included. Reliability was established by means of the generalizability theory. It incorporated rater, replication, and selection facets. RESULTS: Generalizability coefficients ranged from .99 for anterior teeth to .80 for posterior teeth. The main sources of error were associated with rater and selection facets. The replication facet was a minor source of error. CONCLUSIONS: This videographic method is reliable for measurement of tooth display and lip position in spontaneous and posed smiling and speaking. Application of the method is warranted especially when obtaining an emotional smile is difficult, such as cleft lip and palate or disfigured patients. PMID- 17346579 TI - Acrylic removable appliances: comparative evaluation of different postpolymerization methods. AB - INTRODUCTION: In orthodontics, the polymeric part of removable orthodontic appliances could be a hazard for patients because high residual monomer contents can lead to allergic reactions. In addition, water uptake, color stability, and mechanical properties are influenced by the degree of conversion. The aim of this investigation was to evaluate the effectiveness of different postpolymerization methods on the properties of removable orthodontic appliance resins. METHODS: A total of 300 rectangular specimens (5 postpolymerization groups: 20 per group) were manufactured of Orthocryl (n = 100, Dentaurum, Ispringen, Germany), Palapress (n = 100, Heraeus-Kulzer, Wehrheim, Germany), and Pro Base Cold (n = 100, Ivoclar-Vivadent, Schaan, Liechtenstein). The first 2 postpolymerization groups were postcured in a stove (10 minutes at 40 degrees C or 80 degrees C). The third resin group was postcured in a microwave at 600W for 5 minutes, and the fourth polymer group was postcured in a microwave at 600W for 10 minutes. Twenty conventionally cured samples (cold-curing under pressure: water bath 40 degrees C, 25 minutes, 2.2 bar) were the control group. Water sorption, fracture toughness, and Vickers hardness were measured. RESULTS: Fracture toughness and Vickers hardness of the resins are slightly increased after curing. Heat as a secondary curing method decreases water uptake of resins used for removable orthodontic appliances. CONCLUSIONS: Heat postpolymerization appears to improve the properties of removable orthodontic appliance resins. PMID- 17346580 TI - Three-dimensional measurement of residual adhesive and enamel loss on teeth after debonding of orthodontic brackets: an in-vitro study. AB - INTRODUCTION: The purpose of this study was to evaluate 3-dimensionally the changes on tooth surfaces after debonding orthodontic brackets and after removing residual adhesive and finishing. METHODS: Sixty premolars were randomly divided into 2 groups, and brackets were bonded according to the manufacturers' instructions. Two types of orthodontic adhesives were used: resin-modified glass ionomer cement (group 1) and resin-coated adhesive precoated brackets (group 2). The brackets were debonded on a testing machine at a cross-head speed of 1 mm per minute. Models were made of each tooth before bonding, after debonding, and after removal of residual adhesive. The models were scanned with a 3-dimensional laser scanning machine, and the scanned images were analyzed by using modified analytical software. RESULTS: The Mann-Whitney test showed significant differences in adhesive thickness and enamel loss between the 2 groups (P <.001). The mean (+/- SD) thickness for group 1 was 31.2 microm (+/- 26.5 microm), and the mean (+/- SD) thickness for group 2 was 102.7 microm (+/- 79.71 microm). The means (+/- SD) for enamel losses after cleaning and finishing the enamel surfaces were 22.8 microm (+/- 17.67 microm) for group 1 and 50.5 microm (+/- 31.27 microm) for group 2. CONCLUSIONS: Adhesive thickness and enamel loss due to orthodontic procedures can successfully be measured in vitro by using 3 dimensional laser scanning technology. PMID- 17346581 TI - A comparison of treatment impacts between Invisalign aligner and fixed appliance therapy during the first week of treatment. AB - INTRODUCTION: The aim of this study was to evaluate the differences in quality of life impacts between subjects treated with Invisalign aligners (Align Technology, Santa Clara, Calif) and those with fixed appliances during the first week of orthodontic treatment. METHODS: A prospective, longitudinal cohort study involving 60 adult orthodontic patients (33 with Invisalign aligners, 27 with fixed appliances) was completed by using a daily diary to measure treatment impacts including functional, psychosocial, and pain-related outcomes. A baseline survey was completed before the start of treatment; diary entries were made for 7 consecutive days to measure various impacts of the subjects' orthodontic treatment over time. The data were then analyzed for differences between treatment modalities in terms of the subjects' reported impacts from their orthodontic treatment. RESULTS: The baseline mean values did not differ between groups for pain reports (P = .22) or overall quality of life impact (P = .51). During the first week of treatment, the subjects in the Invisalign group reported fewer negative impacts on overall quality of life (P <.0001). The Invisalign group also recorded less impact in each quality of life subscale evaluated (functional, psychosocial, and pain-related, all P <.003). The visual analog scale pain reports showed that subjects in the Invisalign group experienced less pain during the first week of treatment (P <.0001). The subjects in the fixed appliance group took more pain medications than those in the Invisalign group at days 2 and 3 (both P <.007). CONCLUSIONS: Adults treated with Invisalign aligners experienced less pain and fewer negative impacts on their lives during the first week of orthodontic treatment than did those treated with fixed appliances. PMID- 17346582 TI - Orthodontic movement in bone defects filled with xenogenic graft: an experimental study in minipigs. AB - INTRODUCTION: In this study, we investigated whether it is possible to orthodontically move a tooth into an adjacent bone defect previously filled with xenogenic grafting material, with emphasis on the reactions of the tooth roots and adjacent tissues. METHODS: Six minipigs were used. In each animal, 4 defects were created at the mesial aspects of the maxillary and mandibular first permanent molars; the defects on the right were filled with the xenograft (test side), and the opposite defects (control side) were filled with blood clots and allowed to heal spontaneously. Three months later, orthodontic appliances were placed in each quadrant to allow mesial bodily movement of the first permanent molars. When the teeth were moved about halfway into the defect spaces, the animals were killed, and the areas of interest were harvested. The mesial roots of the first molars and adjacent tissues were histologically and morphometrically evaluated. The volume density of bone tissue, the percentage of root resorption, and the bone height were evaluated with image analysis software. RESULTS: Data analysis showed that (1) the percentage of root resorption was smaller (P = .0359) for the test group (4.16%) compared with the control (6.52%); (2) there was no statistically significant differences between groups concerning the volume density of neoformed bone (P >.05); (3) the bovine bone matrix was almost totally replaced by structured bone tissue; (4) the test group had a statistically significant smaller bone height loss (2.18 mm, P = .0018) than the control group (3.26 mm). CONCLUSIONS: Based on these results, it was concluded that teeth can be moved into areas of bone defects previously filled with xenograft. PMID- 17346583 TI - A revision of the adult intraoral radiograph protocol for ABO clinical examinations. PMID- 17346584 TI - Pitch, roll, and yaw: describing the spatial orientation of dentofacial traits. AB - The value of systematically enhancing the Angle classification by including transverse and vertical characteristics in addition to anteroposterior relationships for the face and the dentition is universally accepted. Three aeronautical rotational descriptors (pitch, roll, and yaw) are used here to supplement the planar terms (anteroposterior, transverse, and vertical) in describing the orientation of the line of occlusion and the esthetic line of the dentition. Each of the latter traits affects the modern clinical practice of orthodontics because of its greater focus on dentofacial traits beyond the correction of malocclusion. Consistent with the principle that every orthodontic intervention should begin with a thorough consideration of variation in a patient's dentofacial traits, this article offers further refinement of diagnostic description and classification. PMID- 17346585 TI - Bisphosphonate treatment: an orthodontic concern calling for a proactive approach. AB - The purpose of this article is to raise awareness among orthodontists of the effects of bisphosphonates, a commonly prescribed type of drug that can inhibit tooth movement and increase serious osteonecrosis risks in the alveolar bones of the maxilla and the mandible. Common medical uses of bisphosphonates, applicable pharmacology, pharmacokinetics, reports of impaired bone healing and induced osteonecrosis, and a drug effect accumulation theory are reviewed. Potential orthodontic issues and proposed orthodontic recommendations for intravenous and oral bisphosphonate treatments are discussed. Bisphosphonate medication screening, patient counseling, informed consent, and, perhaps, changes in treatment planning might be considered. PMID- 17346586 TI - Orthodontic treatment of patients using bisphosphonates: a report of 2 cases. AB - The pharmacologic agent bisphosphonate has recently received much attention in the dental literature. Bisphosphonates in oral or intravenous forms are used to treat various diseases such as certain cancers, bone- and calcium-related disorders, osteoporosis, and osteopenia. Bisphosphonates inhibit bone turnover and result in increased bone-mineral density. The most serious dental side effect of bisphosphonate treatment (particularly when it is administered intravenously) is, paradoxically, osteonecrosis of the mandible or the maxilla represented by exposed nonhealing bone. Other related complications include decreased bone healing and inhibition of orthodontic tooth movement. This article reports the orthodontic treatment of 2 patients who were taking bisphosphonates. PMID- 17346587 TI - Forecasting the timing of peak mandibular growth in males by using skeletal age. AB - INTRODUCTION: It is generally believed that the orthodontic treatment of a patient with a Class II malocclusion and a small mandible is enhanced by good growth at puberty, so that the timing of peak mandibular growth at puberty becomes of interest. METHODS: To test the belief that skeletal age, whether early, average, or late, can be used to predict the timing of maximum growth of the mandible, whether early, average, or late, the predictive relationship between skeletal age and peak mandibular growth velocity (PMdV) at puberty was evaluated in 94 boys by using their longitudinal records from 4 to 18 years of age. Skeletal age was determined for each subject at ages 9 through 14 by using the method of Greulich and Pyle. RESULTS: At age 9, the Greulich and Pyle measurements predicted that 30 of the 94 subjects would have delayed PMdV equal to or exceeding 1 SD (of the mean age for PMdV), and 10 would have advanced PMdV equal to or exceeding 1 SD. When the actual age of PMdV was determined retrospectively from plots of annual mandibular growth increments, it was found that only 4 of the 30 in the delayed group had actually experienced delays in PMdV, and only 2 of the 10 in the advanced group had experienced accelerated PMdV. CONCLUSIONS: Skeletal age is not a reliable predictor of the timing of PMdV. PMID- 17346588 TI - A new craniofacial diagnostic technique: the Sydney diagnostic system. AB - INTRODUCTION: A new nonradiographic craniofacial imaging technique is described and evaluated. The Sydney diagnostic system (SDS) image is formed from a standardized lateral head digital photograph and a standardized digital photograph of the study models. The SDS image was designed for orthodontic diagnosis and treatment planning without a lateral cephalogram. METHODS: Measurements from the composite facial and study model images of 35 randomly selected patients were compared with the same measurements from cephalograms to assess their validity and reliability. The measurements involved soft-tissue profile landmarks, landmarks on the ear, and hard-tissue landmarks identified on the study models including Point A, Point B, and dental landmarks. RESULTS AND CONCLUSIONS: The new imaging technique is reliable and valid for orthodontic treatment planning when compared with a lateral cephalogram if the inherent distortion between images is considered. Most soft-tissue measurements were more reliable than hard-tissue measurements, but some soft-tissue landmarks were less reliable. The ear was a reliable soft-tissue landmark. Maxillary incisor edge was the most reliable hard-tissue landmark, and neither Point A nor Point B could reliably be found on the study model images. PMID- 17346589 TI - Remodeling of alveolar bone crest after molar intrusion with skeletal anchorage system in dogs. AB - INTRODUCTION: The aim of this study was to clarify the influence of supra alveolar fibers on alveolar bone crest remodeling when several teeth are intruded simultaneously. METHODS: The skeletal anchorage system was used to bilaterally intrude the second and third premolars of 10 beagles; supracrestal fiberotomies were performed on 1 side only. RESULTS: The amount of intrusion was greater and the amount of alveolar bone resorption was smaller in the fiberotomy group compared with the nonfiberotomy group. The health status (pocket depth <3 mm) of the dentogingival unit was maintained in the nonfiberotomy group during the experimental period. In the fiberotomy group, the number of osteoclasts on the marginal alveolar crest was less than in the nonfiberotomy group. The dense fiber bundles connecting the second and third premolars and the gingival attachments were maintained in the nonfiberotomy group. CONCLUSIONS: Pressure from the supra alveolar fibers generated by segmental molar intrusion with the skeletal anchorage system induced alveolar bone crest resorption and remodeling, and, as a result, it prevented deepening of the gingival pocket. Periodontal status was good during tooth intrusion. PMID- 17346590 TI - A computed tomographic image study on the thickness of the infrazygomatic crest of the maxilla and its clinical implications for miniscrew insertion. AB - INTRODUCTION: The purpose of this study was to measure the thickness of the infrazygomatic (IZ) crest above the maxillary first molar at different angles and positions to the maxillary occlusal plane. These measurements were then used to derive clinical implications and guidance for inserting miniscrews in the IZ crest without injuring the mesiobuccal root of the maxillary first molar. METHODS: Computed tomographic images of 16 adults were used. For each subject, on the coronal slice of the computed tomographic image containing the IZ crest and mesiobuccal root of the maxillary first molar, the IZ crest thickness and the miniscrew insertion position were measured by postulating that the miniscrew would be inserted at each 5 degrees increment from 40 degrees to 75 degrees to the maxillary occlusal plane. RESULTS: The IZ crest thickness above the maxillary first molar ranged from 5.2 +/- 1.1 mm to 8.8 +/- 2.3 mm, measured at 40 degrees to 75 degrees to the maxillary occlusal plane and 13 to 17 mm above the maxillary occlusal plane. CONCLUSIONS: By adopting 6 mm as the minimal IZ crest thickness for sustaining a miniscrew well throughout treatment and avoiding injury to the mesiobuccal root of the maxillary first molar, the clinical implication for miniscrew placement in the IZ crest of an adult is to insert it 14 to 16 mm above the maxillary occlusal plane and the maxillary first molar at an angle of 55 degrees to 70 degrees to the maxillary occlusal plane. PMID- 17346591 TI - Occlusal contacts with different retention procedures in 1-year follow-up period. AB - INTRODUCTION: The aim of this follow-up study was to evaluate the number of contacts in centric occlusion during a 1-year retention period in patients treated with 2 retention procedures and in a control sample. METHODS: Twenty patients received modified wraparound Hawley retainers, and 20 received maxillary Jensen plates with mandibular fixed retainers. These retention patients were compared with a control group of 20 subjects with normal occlusions. Silicone based impression bites were used to record occlusal contacts. Paired and independent-sample t tests were used to evaluate intragroup and intergroup differences. RESULTS: Contacts increased in the total arch and the posterior combined (actual/near) during the retention period compared with the control group. In the Hawley retainer group, actual contacts on the second molars (P <.05), near contacts on the premolars (P <.05), and total contacts on the first molars (P <.05) and premolars (P <.01) had statistically significant increases. In the maxillary Jensen plate and mandibular fixed lingual retainer group, the number of actual contacts on the posterior segment increased. Actual contacts on the first molars (P <.01), second molars (P <.01), premolars (P <.05), and canines (P <.05), and total contacts on the first (P <.05) and second (P <.05) molars had statistically significant increases. During the observation period, some slight occlusal changes were seen in the control sample, presumably from growth and development. At the end of the study, during the 1-year follow-up period, no statistically significant occlusal contact differences were observed in the 3 groups. CONCLUSIONS: Retention procedures carried out in this study allowed relative vertical movement of the posterior teeth. PMID- 17346592 TI - Leveling the curve of Spee with a continuous archwire technique: a long term cephalometric study. AB - INTRODUCTION: The orthodontic technique favored by a clinician frequently determines how a deep curve of Spee (COS) is leveled. The primary purpose of this investigation was to confirm radiographically the long-term effectiveness of a continuous archwire technique--the Alexander discipline--in leveling the COS in patients with Class II Division 1 deep-bite malocclusions treated without extractions. METHODS: The sample for this retrospective cephalometric study consisted of the randomly selected orthodontic records of 31 subjects (22 female, 9 male) treated with the continuous archwire technique in the private practice of Dr R.G. "Wick" Alexander in Arlington, Texas. RESULTS: The mean pretreatment COS for this sample was 2.47 mm, and the corresponding mean posttreatment COS was 0.19 mm. The COS was completely level in 21 patients after treatment, and the rest had slight residual COS at the end of this phase. Ten of the 31 subjects remained level from 5 to 25 years after orthodontic treatment. CONCLUSIONS: The results indicate that most leveling was accomplished by the extrusion of the premolars. The continuous archwire technique is effective in leveling the COS in patients with Class II Division 1 deep-bite malocclusions treated without extractions when the initial COS is 2 to 4 mm. The leveling of the COS with the continuous archwire technique takes place by a combination of premolar extrusion and, to a lesser extent, incisor intrusion. PMID- 17346593 TI - Effects of bimaxillary surgery and mandibular setback surgery on pharyngeal airway measurements in patients with Class III skeletal deformities. AB - INTRODUCTION: The purpose of this study was to compare the short-term and long term effects of bimaxillary surgery with those of mandibular setback surgery concerning pharyngeal airway measurements at 3 levels: nasopharynx, oropharynx, and hypopharynx. METHODS: The sample included 66 Japanese women in 2 groups who had been diagnosed with Class III skeletal deformities and had undergone surgical orthodontic treatment. Those in group A (35 patients) underwent bilateral sagittal split ramus osteotomies; those in group B (31 patients) underwent LeFort I procedures with bilateral sagittal split ramus osteotomies. Lateral cephalograms were assessed within 6 months before surgery and at short-term (3-6 months after surgery) and long-term (at least 2 years after surgery) follow-ups. RESULTS: In group A, the pharyngeal airway was constricted significantly at the oropharyngeal and hypopharyngeal levels at both the short-term and the long-term follow-ups. In group B, significant changes were shown at the 3 pharyngeal levels at the short-term follow-up, whereas no significant changes were shown at the long-term follow-up. CONCLUSIONS: These results indicate that, when possible, bimaxillary surgery rather than only mandibular setback surgery is preferable to correct a Class III deformity to prevent narrowing of the pharyngeal airway space, a possible predisposing factor in the development of obstructive sleep apnea. PMID- 17346594 TI - Gingival temperature measurements with fluoride and nonfluoride elastomeric ligatures. AB - INTRODUCTION: Little is known about the effect of fluoridated elastomerics on gingival health. The aim of this in-vivo study was to compare subgingival temperature measurements near brackets with fluoridated elastomerics with nonfluoridated elastomerics. METHODS: This was a prospective, longitudinal, crossover study, involving 12 volunteers. Data, including gingival temperature, gingival crevicular fluid volume, and gingival index scores, were collected weekly from the buccal aspects of 8 teeth for 8 weeks (except for a 1-week washout period). A baseline examination was carried out at week 1. This was repeated at week 2, immediately before placement of orthodontic brackets on all 4 first premolars, which were randomly allocated to receive either fluoridated or nonfluoridated elastomerics. Examinations were repeated at weeks 3 and 4, when the elastomerics were removed. After the washout period, the contrary elastomerics (either fluoridated or nonfluoridated) were placed. Examinations were repeated at weeks 5 and 6 when the elastomerics and brackets were removed. A final examination was performed at week 7. RESULTS: There was a small, but statistically significant, increase in the gingival temperature (P = .002) after placement of the fluoridated elastomerics. There were no other differences in the markers for gingival health. CONCLUSIONS: The mean increase in gingival temperature with fluoridated elastomers was small (0.3 degrees C) and unlikely to be clinically significant, but the implications are discussed. PMID- 17346595 TI - In-vivo and in-vitro comparison of bond strengths of orthodontic brackets bonded to enamel and debonded at various times. AB - INTRODUCTION: The purpose of this study was to measure and compare in-vivo and in vitro bond strengths of orthodontic brackets bonded to human enamel and debonded at various times. An in-vivo debonding device was validated and used to measure bond strengths in the oral environment. METHODS: For the in-vitro study, mini twin metallic premolar brackets (Opti-mesh XRT, Oromco Corp, Glendora, Calif) precoated with Transbond XT composite resin (3M Unitek, Monrovia, Calif) were bonded to 60 extracted premolars. The teeth were divided into 4 groups of 15, and shear bond strength was tested on a universal testing machine at 4 time periods: 10 minutes, 24 hours, 1 week, and 4 weeks. For the in-vivo test, 60 premolars in 22 volunteers (dental students) from King Saud University were bonded with Mini Twin metallic premolar brackets and divided into 4 groups; bond strengths were measured at 10 minutes, 24 hours, 1 week, and 4 weeks. RESULTS: Statistical analysis with 1-way ANOVA at P <.05 showed no significant differences among the in-vitro or the in-vivo groups. Two-way ANOVA at P <.05 was used to compare the in-vitro results with the in-vivo results; the in-vivo group had significantly lower mean bond strength values. In addition, survival analysis, used to calculate the probability of bond failure at P <.05, confirmed the significant difference between in-vitro and in-vivo environments. CONCLUSIONS: Reported bond strength values are not time dependent. PMID- 17346596 TI - Effect of blood and saliva contamination on bond strength of brackets bonded with a protective liquid polish and a light-cured adhesive. AB - INTRODUCTION: The application of a polymer coating to the labial enamel tooth surface before bonding can help keep white spot lesions from forming. Previous studies evaluating the effects of blood and saliva contamination on the bond strengths of light-cured composites showed significant reductions in bond strength values. The purpose of this study was to investigate whether the bond strength of a light-cured system (Transbond XT, 3M Unitek, Puchheim, Germany) used with a liquid polish (BisCover, Bisco, Schaumburg, Ill) is affected by contamination with blood or saliva. METHODS: One hundred twenty permanent human premolars were randomly divided into 6 groups of 20. Various enamel surface conditions were studied: dry, blood contaminated, and saliva contaminated. A light-cured bonding system (Transbond XT) was used in all groups. The teeth in group 1 were bonded with Transbond XT. In the second group, BisCover polymeric resin polish was applied on the etched tooth surfaces before the brackets were bonded with Transbond XT resin. Comparison of the first and second groups showed no statistically significant difference. Groups 3 through 6 were bonded without Transbond XT. For groups 3 and 5, a layer of blood or saliva, respectively, was applied to the etched enamel followed by BisCover. In groups 4 and 6, blood or saliva, respectively, was applied on the light-cured BisCover. Shear forces were applied to the samples with a universal testing machine, and bond strengths were measured in megapascals. RESULTS: The protective liquid polish (BisCover) layer did not affect bond strength. CONCLUSIONS: Blood contamination on acid-etched surfaces affects bond strength more than saliva contamination. When a protective liquid polish (BisCover) is applied to the tooth surface, the effect of contamination by blood or saliva is prevented. PMID- 17346597 TI - Treatment efficiency of conventional vs self-ligating brackets: effects of archwire size and material. AB - INTRODUCTION: In this prospective clinical study, we assessed the relative speed of archwire changes, comparing self-ligating brackets with conventional elastomeric ligation methods, and further assessed this in relation to the stage of orthodontic treatment represented by different wire sizes and types. METHODS: The time taken to remove and ligate archwires for 131 consecutive patients treated with either self-ligating or conventional brackets was prospectively assessed. The study was carried out in the orthodontic department of a district general hospital in the United Kingdom. The main outcome measure was the time to remove or place elastomeric ligatures or open/close self-ligating brackets for 2 matched groups of fixed appliance patients: Damon2 self-ligating bracket (SDS Ormco, Orange, Calif) and a conventional mini-twin bracket (Orthos, SDS Ormco). The relative effects of various wire sizes and materials on ligation times were investigated. The study was carried out by 1 operator experienced in the use of self-ligating and conventional brackets. RESULTS: The Damon2 self-ligating system had a significantly shorter mean archwire ligation time for both placing (P <.001) and removing (P <.01) wires compared with the conventional elastomeric system. Ligation of an archwire was approximately twice as quick with the self ligating system. Opening a Damon slide was on average 1 second quicker per bracket than removing an elastic from the mini-twin brackets, and closing a slide was 2 seconds faster per bracket. This difference in ligation time between the Damon2 and the conventional mini-twin brackets became more marked for larger wire sizes used in later treatment stages. CONCLUSIONS: The type of bracket and the size of wire used are statistically significant predictors for speed of ligation and chairside time. The self-ligating system offered quicker and arguably more efficient wire removal and placement for most orthodontic treatment stages. PMID- 17346598 TI - Resistance to sliding of titanium brackets tested against stainless steel and beta-titanium archwires with second-order angulation in the dry and wet states. AB - INTRODUCTION: With the increased awareness of Ni allergies, alternative alloys for orthodontic products must be identified. The properties of these new products must be determined. METHODS: Rectangular (0.017 x 0.025 in) stainless steel (SS) and beta-titanium (beta-Ti) archwires were tested against commercially pure titanium brackets (CP-Ti, 0.018-in slot) in the dry state and with whole human saliva. Resistance to sliding (RS) was measured as a function of 5 normal forces (N, 200 to 950 cN), 32 angles (theta, -12 degrees to +12 degrees), and 1 interbracket distance (IBD, 18 mm). RESULTS: With clearance between the archwire and the bracket (passive region, theta < or =theta(c)), the frictional coefficients (mu) of the SS archwire and the CP-Ti bracket couples were 0.12 and 0.13 for the dry and wet tests, respectively; for the beta-Ti archwire and the CP Ti bracket couples, the mu values were 0.29 and 0.28 for the dry and wet tests, respectively. For an theta without clearance (active region, theta > or =theta(c)), RS increased as a function of theta and N. To examine the rates of binding (mu(BI)) in this active region, the value of classical friction (mean of the passive region data) was subtracted from RS to yield BI, and the value of theta(c) was subtracted from each theta to yield relative contact angles (theta(r)). Because of the unique relationship between the frictional and mechanical properties of these SS and beta-Ti archwires tested against the CP-Ti brackets at a large IBD, the mu(BI) values for these archwire-bracket couples were nominally equivalent (24 to 30 cN per degree). Clinical outcomes would be unaffected by this 6 cN per degree (approximately 0.2 oz-force per degree) difference. When all kinetic data in the elastic region (theta(r) < or =5 degrees ) were combined, mu(BI) equaled 28 cN per degree. Above this region (theta(r) > or =5 degrees ), the data for the SS archwire and CP-Ti bracket couples were less scattered than those for the beta-Ti archwire and the CP-Ti bracket couples. This demarcation from linearity was designated as theta(z) and indicated the end of the elastic region and the beginning of the plastic region, above which sliding can eventually cease. This region (theta > or =theta(z)), the binding region (theta(c) < or =theta < or =theta(z)), and the classical friction region (theta < or =theta(c)) were described in a model. CONCLUSIONS: This model explains, in part, the equivalent values of mu(BI) for SS and beta-Ti archwires tested against CP-Ti brackets. PMID- 17346599 TI - Friction does not increase anchorage loading. AB - Conventional wisdom suggests that orthodontists must apply added force to overcome friction during canine retraction (sliding mechanics), the result of which can be increased anchorage loading and anchorage loss. However, for a frictional force to be exerted mesially by the archwire against a canine during retraction, the archwire must be compressed between the canine and the anchor molar, and an equal but opposite force must be applied distally against the molar by the archwire. In other words, the frictional force that reduces the force of retraction on the canine must also reduce the protraction force on the molar. Emphasis on employing reduced-friction (eg, self-ligating) brackets during sliding mechanics to prevent added posterior anchorage loading is unwarranted and based more on bracket salesmanship than on orthodontic biomechanics. PMID- 17346600 TI - Mandibular distraction osteogenesis in a skeletal Class II patient with obstructive sleep apnea. AB - We report the orthodontic treatment of a 31-year-old man with severe skeletal Class II malocclusion and documented obstructive sleep apnea (OSA). He had a retrognathic profile with an overbite of 4 mm and an overjet of 14 mm. Mandibular distraction osteogenesis was performed to lengthen the small, retruded mandible by 18 mm and improve the symptoms of OSA. Orthodontic treatment after the mandibular distraction osteogenesis procedure lasted 3 years 1 month. An acceptable occlusion was obtained, and the patient's OSA was significantly alleviated. Although the patient was satisfied with the treatment, condylar resorption was observed. The relevance of condylar resorption with reference to a comprehensive evaluation of the treatment outcome is discussed. PMID- 17346601 TI - Three-dimensional reconstruction of individual cervical vertebrae from cone-beam computed-tomography images. AB - INTRODUCTION: The visualization of cervical vertebral morphology has potential in skeletal age assessment; however, thus far, it has only been described in planar images. The objective of this article is to present a novel segmentation algorithm for automatic 3-dimensional (3D) reconstruction of individual cervical vertebrae from cone-beam computed-tomography (CBCT) volumetric data sets. METHODS: CBCT data sets of 3 subjects representing different skeletal age groups with no potential health influences on cervical anatomy were identified from a larger subject sample. A visualization toolkit was used to demonstrate the surface topologic shape of cervical vertebrae C1 through C3. The cervical vertebrae were segmented by using a custom algorithm based on individual voxel intensity distribution analysis and propagation from a densitometric start point to generate the whole vertebra. The segmentation algorithm was combined with toolkit visualization to render and save the cervical vertebra in 3D space. RESULTS: The developed segmentation algorithm separated individual cervical vertebrae successfully. It was robust and efficient. Observed 3D cervical vertebral morphologic features from the 3 examples matched the known 2 dimensional sagittal shape changes of the cervical vertebra with respect to subject age and skeletal maturation. CONCLUSIONS: Segmentation of individual vertebrae proved possible from CBCT volumetric data sets. This provides a 3D approach to the biologic aging of orthodontic patients by using images of the cervical spine. It also has potential in studying disease processes such as spinal fractures consequent to osteoporosis. PMID- 17346602 TI - Litigation, legislation, and ethics. What's in a name? PMID- 17346603 TI - Strength of evidence in qualitative research. PMID- 17346604 TI - Limitations are not properly acknowledged in the scientific literature. AB - Limitations are important to understand for placing research findings in context, interpreting the validity of the scientific work, and ascribing a credibility level to the conclusions of published research. This goes beyond listing the magnitude and direction of random and systematic errors and validity problems. Acknowledgment of limitations requires an interpretation of the meaning and influence of errors and validity problems on the published findings. An examination of the full-text files of the first 50 articles published in 2005 in the six most-cited research journals and in two recently launched leading open access journals showed that only 67 articles (17%) used at least one word denoting limitations in the context of the presented scientific work. Only four articles (1%) used the word limitation in their abstract; none referred to limitations of the present work that materially affected conclusions. Only five articles had a separate section on limitations. Conversely, 243 articles (61%) used words detected by the roots error, valid, bias, reproducib, or false and 289 articles (72%) used words with the root importan. Among the 25 top-cited journals' instructions to the authors and editorial policies, only one encourages discussion of limitations; importance, novelty, and lack of error are typically encouraged. Limitations should be better covered and discussed in research articles. To facilitate this, journals should give better guidance and promote the discussion of limitations. Otherwise, we are facing an important loss of context for the scientific literature. PMID- 17346605 TI - Hypertension patients participating in trials differ in many aspects from patients treated in general practices. AB - OBJECTIVE: To determine to what extent participants in randomized controlled hypertension trials (RCTs) could be compared to patients with hypertension in general practices. STUDY DESIGN AND SETTING: We analyzed RCTs that had been used in hypertension guidelines or were available for future hypertension guidelines. The characteristics of the participants of these RCTs were compared with those of the patients with hypertension in general practices. In addition, inclusion and exclusion criteria of the RCTs were applied to the hypertension patients in the general practices. RESULTS: Twenty-one trials were analyzed. Participants' characteristics often differed from those of the patients with hypertension in general practices, in particular in the older trials where the participants showed lower cardiovascular risk. More recent trials showed participants' profiles that better reflected those of the patients under treatment in a general practice. Less than half of the patients undergoing treatment in a general practice would have been included in the hypertension trials. CONCLUSION: Participants taking part in trials differed from patients with hypertension in a general practice in a number of important aspects. This hampers their external validity. Inclusion of participants with comorbidity and other general practice characteristics would improve translation of study findings to daily practice recommendations. PMID- 17346606 TI - Hip protectors decrease hip fracture risk in elderly nursing home residents: a Bayesian meta-analysis. AB - OBJECTIVE: To design a Bayesian random effects model for pooling binary outcome data from cluster randomized trials (CRTs) with individually randomized trials (IRTs) and then use this model to determine if hip protectors decrease the risk of hip fracture in elderly nursing home residents. STUDY DESIGN AND SETTING: Eight electronic databases were searched; abstracts and papers were reviewed in duplicate. Randomized controlled trials of hip protectors in nursing homes were included. The pooled mean odds ratio (OR) of a hip fracture in an individual allocated to hip protectors with 95% credibility interval (CRI) was calculated. RESULTS: We included four trials of 1,922 individuals (including three CRTs). The pooled OR of an elderly nursing home resident sustaining one or more hip fractures with hip protector allocation was 0.40 (95% CRI 0.25, 0.61). The model was robust in multiple sensitivity analyses assuming alternative intracluster correlation coefficient values. CONCLUSION: The Bayesian approach may be used in meta-analyses of IRTs and CRTs. Using this approach, we have determined that hip protectors decrease the risk of hip fracture in elderly nursing home residents. Methodologic limitations of the included trials and a possible herd effect in CRTs may have influenced these results. PMID- 17346607 TI - Cox regression was used to compare the measurement error of two tests vs. a gold standard. AB - OBJECTIVE: The use of survival analysis has been proposed to compare the diagnostic performance of two tests. We expanded it to compare two tests with a gold standard simultaneously. STUDY DESIGN AND SETTING: In this diagnostic study, the spherical equivalent component of refraction was measured with the PowerRefractor and the Canon R-50 autorefractor. The reference test was Canon R 50 autorefraction with cycloplegic blockage of accommodation. The error of the two index tests was compared with Cox regression analysis with robust standard error estimation to take into account repeated measures on the same subject. We evaluated 1,559 children aged 5-6 from 25 schools in three urban locations in Ecuador. RESULTS: The main strength of survival analysis was that it does not assume a specific distribution of measurement errors, which were not normally distributed in this study. The proportional hazards assumption, a requirement of Cox regression, was met only after removal of the bias of each test. When this was done, noncycloplegic autorefraction was better than the PowerRefractor regardless of the magnitude and direction of the error. CONCLUSION: The potential of Cox regression can be applied to diagnostic studies that compare more tests with a gold standard. PMID- 17346608 TI - Analysis of case-cohort data: a comparison of different methods. AB - OBJECTIVE: The case-cohort design combines the advantages of a prospective cohort study and the efficiency of a case-control design. Usually a Cox proportional hazards model is used for the analyses. However, adaptation of the model is necessary because of the sampling. We compared three methods that were proposed in the literature, which differ in weighting of study subjects: Prentice's, Barlow's, and Self and Prentice's method. STUDY DESIGN AND SETTING: In a cohort of 17,357 women we studied the relationship between body mass index and cardiovascular disease (n=821) with varying subcohort sizes (sampling fraction=0.005, 0.01, 0.05, 0.10, 0.15). RESULTS: Even with a sampling fraction of 0.01, all three methods showed identical estimates and standard errors (SE). With sampling fractions >or=0.10, results of the case-cohort analyses were similar to the full-cohort analyses. With simulations, the three methods provided different results if the full cohort is small (<1,250 subjects, subcohort=10%, 8% failures) or if the subcohort size was smaller than 15% (full cohort of 1,000 observations, 8% failures). The difference between the methods did not change with the number of failures or with different effect sizes. CONCLUSION: In the above-mentioned situations, the effect estimates and SE of Prentice's method most resembled the estimates of the full-cohort estimates. PMID- 17346609 TI - A one-item question with a Likert or Visual Analog Scale adequately measured current anxiety. AB - OBJECTIVE: To determine whether a single question with a Likert Scale or a Visual Analog Scale (VAS) response adequately measures current anxiety. STUDY DESIGN AND SETTING: Consecutive English-speaking adult women attending a dedicated breast clinic in a major Australian city were invited to complete a demographic questionnaire, the State Trait Anxiety Inventory (STAI), and a single question with a five-point Likert Scale response and a VAS in random order. Only women who completed the STAI were included in analyses. RESULTS: Four hundred of 497 (80%) eligible women agreed to participate. Both measures were adequate predictors of the STAI score; correlation with STAI was 0.78 (95% confidence interval [CI] 0.73 0.82) for the VAS and 0.75 (95% CI 0.70-0.79) for the Likert Scale. However, 11% of women incorrectly completed the VAS limiting its usefulness. CONCLUSION: A single question with either a Likert Scale or VAS response may be an adequate replacement for the STAI. Both measures quickly and easily assess anxiety and may be useful for research purposes when researchers have very limited time or questionnaire space or need to reduce the burden on participants of completing many measures. PMID- 17346610 TI - Relative-risk ratio was a useful measure of differential association in cohort and case-series studies. AB - OBJECTIVE: The framework consists of cohort or case-series studies with intermittent exposure and two types of events. The aim is to define and estimate an association measure between the exposure and the occurrence of one type of event rather than the other. STUDY DESIGN AND SETTING: The model and the estimation method are obtained by extending Farrington's approach for one type of recurrent event. The proposed association measure "RR(c)" is the ratio of the relative risks pertaining to each type of event. The estimated RR(c) and its confidence interval are derived under the independence assumption between the counts of the two types of events. The data that are analyzed are part of the data of a study on antimicrobial resistance in children. RESULTS: An interpretation of the RR(c) is proposed in terms of an odds ratio, which parallels a similar association measure defined in cross-sectional studies ("OR(c)"). The estimated value of the RR(c) agrees with the OR(c) reported in previous studies. CONCLUSION: The RR(c) appears as a useful tool for evaluating the risk of colonization (or infection) with resistant rather than susceptible bacteria following a previous intake of a given antibiotic conditional on colonization (or infection) with any bacteria. PMID- 17346611 TI - Item response bias was present in instrumental activity of daily living scale in Asian older adults. AB - OBJECTIVE: Item response bias (also called differential item functioning, DIF) in Instrumental Activities of Daily Living (IADL) occurs when members of different groups possessing the same disability level do not have the same probability of responding positively for a given item(s). This study aimed to identify the extent of DIF by gender, age, ethnicity, and dementia groups in IADL estimates in Asian (Chinese, Malays, and Indian) elderly subjects. METHODS: Data of 1,072 noninstitutionalized elderly subjects were analyzed using Multiple-Indicator Multiple-Cause (MIMIC) latent variable modeling. RESULTS: Given the same functional level, older elderly were less likely to report needing help with preparing meals; men were more likely to report needing help with preparing meals, doing laundry, and taking medication; Malays and demented elderly were more likely to report needing help with using the telephone. The impact of DIF on group differences in cognitive IADL was highest for ethnicity (58%), followed by gender (50%), and dementia (23%); whereas 92% and 5% of group differences in physical IADL were for gender and age, respectively. CONCLUSION: Item-response bias in IADL scale by gender, age, ethnicity, and dementia should be considered in direct comparisons of disability status among population groups. PMID- 17346612 TI - A generalized concept of power helped to choose optimal endpoints in clinical trials. AB - OBJECTIVES: A clinical trial may have multiple objectives. Sometimes the results for several parameters may need to be significant or meet certain other criteria. In such cases, it is important to evaluate the probability that all these objectives will be met, rather than the probability that each will be met. The purpose of this article is to introduce a definition of power that is tailored to handle this situation and that is helpful for the design of such trials. STUDY DESIGN AND SETTING: We introduce a generalized concept of power. It can handle complex situations, for example, in which there is a logical combination of partial objectives. These may be formulated not only in terms of statistical tests and of confidence intervals, but also in nonstatistical terms, such as "selecting the optimal by dose." RESULTS: The power of a trial was calculated for various objectives and combinations of objectives. CONCLUSION: The generalized concept of power may lead to power calculations that closely match the objectives of the trial and contribute to choosing more efficient endpoints and designs. PMID- 17346613 TI - Katz' ADL index assessed functional performance of Turkish, Moroccan, and Dutch elderly. AB - BACKGROUND AND OBJECTIVE: We examined the reliability and validity of self reported limitations encountered in the activities of daily living (ADL) as measure of functional performance, for Turkish, Moroccan, and indigenous Dutch elderly in the Netherlands. METHODS: We obtained data on self-reported ADL measured by Katz' ADL index and on five related health outcomes among a general population sample of 304 Dutch, 330 Turkish, and 299 Moroccan respondents aged 55 74 years, in Amsterdam, the Netherlands (response: 60%). RESULTS: Katz' ADL index demonstrated good internal consistencies for each ethnic group (Cronbach's alphas: 0.84-0.94). Regarding validity, the ADL index showed relatively strong associations with related outcomes, that is, long-term limitations in mobility and SF-36 physical functioning (rank correlations: 0.64 and -0.60, respectively). Associations with more general health outcomes, number of chronic disorders, Center for Epidemiologic Studies-Depression scale symptoms, and SF-36 role performance were weaker, as expected. Associations were stronger for Moroccans than for indigenous Dutch elderly regarding both SF-36 outcomes and depressive symptoms. CONCLUSION: Katz' ADL index is valid to assess functional performance of Turkish, Moroccan, and Dutch elderly, but comparisons with Moroccan elderly should be handled with caution. The explanation of these findings and their generalizability to other ethnic groups deserve further study. PMID- 17346614 TI - Information given to postmenopausal women on coronary computed tomography may influence cardiac risk reduction efforts. AB - OBJECTIVE: Cardiovascular disease (CVD) is largely preventable through appropriate risk-factor modification. We sought to compare effects of comprehensive cardiac risk factor screening with and without computed tomography (CT) imaging of the coronary arteries on behavior change related to cardiac risk in postmenopausal women. STUDY DESIGN AND SETTING: 56 postmenopausal women were randomized to alternative screening programs and followed for 1 year. RESULTS: Subjects randomized (n=26) to the CT imaging group were shown images of their coronary arteries and received an interpretation from a radiologist. Most subjects in the CT group had a very low-risk (73.1%) coronary calcification score at baseline. Systolic blood pressure, total cholesterol, triglyceride, LDL, and cholesterol/HDL ratio declined significantly in the conventional screening group, but not in the CT imaging group (P<0.05). As compared to baseline values, study participation lead to significant reductions in total cholesterol, HDL, LDL, and blood pressure at 6 months (P<0.05) and triglyceride (P<0.05) at 12 months. CONCLUSIONS: CVD risk-screening programs can facilitate cardiac risk reduction in women, but these data do not support an independent benefit of coronary CT imaging in a low-to-moderate risk group. The possibility of a deleterious effect of imaging on patient commitment to lifestyle changes is suggested. PMID- 17346615 TI - Veteran's affairs hospital discharge databases coded serious bacterial infections accurately. AB - OBJECTIVES: We sought to test the ability of large health care utilization databases to accurately identify serious bacterial infections and opportunistic infections leading to hospital admission. STUDY DESIGN AND SETTING: We conducted a cross-sectional validation study using patients admitted to hospitals in the administrative database of the Department of Veterans Affairs, VISN 1, between 2001 and 2004. Detailed hospital chart abstraction protocols were developed to define a gold-standard diagnosis of serious bacterial infections and opportunistic infections. Hospital acquired infections were not considered. RESULTS: A total of 158 patients who were hospitalized for selected bacterial infections and 69 patients for opportunistic infections were identified using ICD 9 discharge diagnoses. The positive predictive values (PPV) of identifying specific bacterial infections that lead to hospital admissions varied between 100% and 66%. All conditions combined yielded a PPV of 80%. Once the gold standard definition of bacterial conditions was broadened to hospital admissions due to any acute infectious condition, the PPV increased to 90%. Excluding systemic candidiasis, the average PPV for the selected opportunistic infections was 76%. CONCLUSION: Our findings suggest that ICD-9 codes of selected serious infections from hospital discharge files can be used as substitutes for chart based diagnoses. PMID- 17346616 TI - African American race was associated with an increased risk of complications following venous thromboembolism. AB - OBJECTIVE: Limited data exist on the quality of care for patients with venous thromboembolism (VTE), and it is unknown whether the processes and outcomes of care for this illness differ between African Americans and whites. STUDY DESIGN AND SETTING: We retrospectively studied 168 patients hospitalized for VTE in two Veterans Affairs hospitals during fiscal years 2000-2002. Patient characteristics, information about processes of care, and medical outcomes at 90 days after the index VTE event were abstracted from medical records. We used logistic regression to explore associations between race, processes of care, and the overall 90-day complication rate (i.e., death, bleeding, or recurrent VTE), adjusting for patient baseline characteristics. RESULTS: Multivariable analysis demonstrated that administration of warfarin within 1 day of starting heparin (odds ratio [OR] 0.20, 95% confidence interval [CI]: 0.05-0.42) and overlap of heparin and warfarin treatment >or=4 days (OR 0.09, 95% CI: 0.02-0.50) were associated with a lower complication rate, and African American race was associated with a higher complication rate (OR 5.2, 95% CI: 1.3-21.6). Race was not significantly associated with the performance of processes of care in multivariable analysis. CONCLUSION: Although African Americans had an increased risk of complications following VTE, race was not independently associated with the use of processes of care for VTE. PMID- 17346617 TI - Young men were at risk of becoming lost to follow-up in a cohort of head-injured adults. AB - OBJECTIVE: This study is to identify predictors of loss to follow-up among adults with head injury. STUDY DESIGN AND SETTING: A prospective cohort of 1,857 adults enrolled in the Medical Research Council (MRC) CRASH trial known to be alive 2 weeks after head injury. Six-month follow-up was defined as "overdue" if over 6 months late. Patient information collected at enrollment and after 14 days was used to predict overdue follow-up. A random two-thirds of the cohort was analyzed using logistic regression and binary recursive partitioning. The regression model and decision rule derived by recursive partitioning were evaluated using the remaining third. RESULTS: Overdue follow-up was more likely in patients aged 25 34 years (odds ratio, 1.76; 95% confidence interval [CI]=1.18-2.62), victims of assault (1.63; 1.09-2.45), patients independent after 2 weeks (1.79; 1.18-2.72) and patients for whom postcodes (2.36; 1.65-3.39), telephone numbers (1.82; 1.19 2.79) or general practitioners (1.67; 1.16-2.39) were unknown. Binary recursive partitioning specifically identified males aged younger than 43 years to be at risk. CONCLUSION: Successful follow-up in head-injury studies requires patients' postcodes and telephone numbers to be available. Young men remain at risk of becoming lost to follow-up, presenting a challenge for researchers aiming for complete data. PMID- 17346618 TI - Author's response: a survey identified publication bias in the secondary literature. PMID- 17346619 TI - The structural equation modeling technique did not show a response shift, contrary to the results of the then test and the individualized approaches. PMID- 17346621 TI - Induction therapy in heart transplantation: is there a role? PMID- 17346622 TI - Pig-to-non-human primate heart transplantation: immunologic progress over 20 years. AB - The major developments in pig-to-non-human primate heart xenotransplantation during the past 20 years are summarized, largely through the experience of one investigator. Genetic modifications to organ-source pigs have been important steps in increasing heart xenograft survival from a few minutes in 1986 to 2 to 6 months in 2005. PMID- 17346623 TI - Does total implantability reduce infection with the use of a left ventricular assist device? The LionHeart experience in Europe. AB - BACKGROUND: Infection is the leading cause of death for left ventricular assist device (LVAD) patients with end-stage heart failure. Decreased infection may be possible with fully implantable LVADs such as the LionHeart, which lacks percutaneous conduits (PCs), a common source of device-related infection (DRI). This sub-study reports infections with the LionHeart and compares these results with historic data from the REMATCH trial, bridge to recovery (BTR) and bridge-to transplantation (BTT) studies. METHODS: Twenty-three patients were implanted with the LionHeart LVAD and followed until death or heart transplant during a non randomized, multicenter, European trial from October 1999 to April 2004. The nature and incidence of infection were analyzed and adjudicated to definitions similar to, or the same as, the REMATCH definitions. RESULTS: The combined number of implant days was 7,980, with a mean of 347 days (median 112, range 17 to 1,259 days). Survival at 1 year was 39%, with 2-year survival at 22%. Seventy-four percent of patients developed one or more infections, with 30% developing sepsis, and 35% developing pump-pocket infections (PSIs). No patients developed pump housing or inflow- or outflow-tract infections (PI). For comparison, the prevalence rates of sepsis, PSI and PI in REMATCH were 51%, 35% and 19%, respectively. CONCLUSIONS: The patients in the European LionHeart Clinical Utility Baseline Study (CUBS) trial had less sepsis and less overall DRI compared with the REMATCH LVAD group. Therefore, the fully implanted device may cause less infection than PC devices during destination therapy (DT). Although lower for DT, these rates are still higher than for some BTT experiences. Areas for future improvement include miniaturization of controller/battery components to reduce wound complications related to pocket size, and installation of more modern lithium-ion batteries to decrease the need for re-operations due to battery end of-life. PMID- 17346624 TI - Changes in sarcomeric and non-sarcomeric cytoskeletal proteins and focal adhesion molecules during clinical myocardial recovery after left ventricular assist device support. AB - BACKGROUND: Reverse remodeling can occur after left ventricular assist device (LVAD) support, which is sufficient in some cases to allow explantation of the device without cardiac transplantation. The molecular mechanisms involved remain unknown. A specific pattern of expression of sarcomeric and non-sarcomeric proteins in the myocardium is thought to be essential for normal myocardial function. However, a detailed protein analysis of their role in recovery has not been performed previously. METHODS: Myocardial samples were collected at implantation and explantation in 7 patients with dilated cardiomyopathy who had sufficient recovery for device explantation. Western blotting and immunoprobing were used to quantitate changes in the expression of sarcomeric and cytoskeletal proteins. RESULTS: At implantation, all patients (6 men and 1 woman, age [mean +/ SD] 36.1 +/- 10.4 years) were inotrope-dependent; ejection fraction (EF) was 12.6 +/- 4.6%, cardiac index (CI) was 1.66 +/- 0.5 liters/min/m2 and pulmonary capillary wedge pressure (PCWP) was 26 +/- 6 mm Hg. Mean duration of LVAD support was 333 +/- 235 days. Prior to explantation, EF (pump off for 15 minutes) was 62.7 +/- 11.4%, CI was 2.7 +/- 0.7 liters/min/m2 and PCWP was 10.9 +/- 3.5 mm Hg. At explantation, the following statistically significant increases were noted: myosin heavy chain, 1.90-fold (p < 0.05); sarcomeric actin, 1.80-fold (p < 0.05); alphaII spectrin, 1.40-fold (p = 0.05); troponin C, 1.34-fold (p < 0.05); troponin T, 2.10-fold (p < 0.05); cytoskeletal actinin, 5.16-fold (p < 0.05); and smooth muscle alpha-actin, 4.10-fold (p = 0.05). Although not significant (NS), increases were also seen for: troponin I, 1.27-fold; myosin light chain 1, 1.28 fold; tropomyosin, 1.28-fold; and sarcomeric actinin at 3.24-fold. There was a decrease in talin of 2.01-fold (p = NS) between implant and explant. Vimentin was unchanged. CONCLUSIONS: Our data suggest that reverse remodeling of the myocardium parallels improvements in hemodynamic function in LVAD patients showing clinical myocardial recovery. PMID- 17346625 TI - Chronic respiratory complications in pediatric heart transplant recipients. AB - BACKGROUND: The frequency and spectrum of chronic respiratory complications in pediatric heart transplant recipients have not been extensively studied. The aim of this study was to describe the chronic respiratory complications in 126 consecutive pediatric heart transplant recipients. METHODS: Retrospective review of medical records. RESULTS: Between 1987 and 2005, 126 (64 males and 62 females) heart transplantations were performed at Freeman Hospital, Newcastle upon Tyne, United Kingdom. The median age at transplantation was 7.4 years (range, 0.1-17) and the median length of follow-up was 6.8 years (range, 0-18.2). Twenty-four patients have died, and 36 have been transferred to adult follow-up, leaving 66 under pediatric follow-up. Chronic respiratory complications have been documented in 33 children (50%). Bronchiectasis has been identified in 10 children, and 12 further children have had recurrent lower respiratory tract infections (without bronchiectasis) requiring long-term antibiotic prophylaxis. Of those with infectious complications, 81% underwent transplantation before 4 years and had deficiency of pneumococcal-specific antibody response. Obstructive sleep apnea has occurred in 5 children, sub-glottic stenosis has occurred in 3, and significant compression of the left main stem bronchus related to a disproportionately large donor heart has occurred in 2. One child had marked mosaic attenuation on chest computed tomography scan indicative of small airways disease. CONCLUSION: Chronic respiratory complications are common in pediatric heart transplant recipients. The respiratory prognosis for this complex group of patients is usually good, but long-term follow-up by both a respiratory pediatrician and an immunologist is frequently required. PMID- 17346626 TI - Post-operative nosocomial infections after lung and heart transplantation. AB - BACKGROUND: Thoracic transplant recipients appear to be at high risk for post operative infections. Therefore, we investigated the incidence and risk factors of post-operative nosocomial infections (NIs) in lung and heart transplant recipients. METHODS: From January 2002 to December 2003, a cohort of 208 consecutive thoracic transplant recipients (137 lung transplants [LTx], 51 heart transplants [HTx] and 20 combined transplants [CLTx]) were analyzed for post operative infections and in-hospital mortality. NIs were determined according to CDC definitions. Uni- and multivariate risk factor analyses were performed. RESULTS: Of the 157 NIs, 59 were pneumonia (37.6%), 34 primary sepsis (21.6%), 34 urinary tract (21.6%) and 30 surgical site (19.1%). Despite a total NI incidence of 75.5%, more importantly 56.3% of all patients remained free from any infection. CLTx patients had a higher risk of developing NIs (odds ratio [OR] 4.97; 95% confidence interval [CI] 1.74 to 15.34). Risk factors for NIs were volume reduction procedures in LTx (OR 2.6; 95% CI 1.13 to 6.30) and re-do Tx (OR 5.25; 95% CI 1.41 to 26.8). In LTx patients, pre-operative colonization with gram negative rods was found to be a risk factor for post-transplant pneumonia (OR 3.7; 95% CI 1.19 to 11.37). Presence of NI (OR 2.53; 95% CI 1.07 to 6.25) was a risk factor for mortality, as was cystic fibrosis (OR 3.20; 95% CI 1.27 to 7.92) and ventilation prior to transplantation (OR 4.00; 95% CI 1.28 to 12.09). CONCLUSION: The mortality risk associated with NIs requires close infection surveillance for developing specific preventive anti-infection strategies. PMID- 17346627 TI - Calcineurin inhibitor-free immunosuppression using everolimus (Certican) in maintenance heart transplant recipients: 6 months' follow-up. AB - BACKGROUND: Everolimus is a proliferation signal-inhibitor recently introduced in heart transplant recipients. To date, little is known about calcineurin inhibitor (CNI)-free immunosuppression using everolimus. This study reports the results of CNI-free immunosuppression using everolimus. METHODS: During a continuous 9-month period, 60 heart transplant recipients were enrolled. Reasons for switching to everolimus were side effects associated with prior CNI immunosuppression. All patients underwent standardized switching protocols and completed 6 months of follow-up. Blood was obtained for lipid status, renal function, routine controls, and levels of immunosuppressive agents. Echocardiography and a physical examination were performed on Days 0, 14, 28, and then every 3 months. RESULTS: After switching to everolimus, most patients recovered from the side effects associated with CNIs. Renal function improved significantly after 6 months (creatinine, 2.1 +/- 0.6 vs 1.5 +/- 0.9 mg/dl, p = 0.001; creatinine clearance, 42.2 +/- 21.6 vs 61.8 +/- 23.4 ml/[min x 1.73 m2], p = 0.018). Arterial hypertension improved after 3 months and remained decreased during the observation period. Tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved. Adverse events occurred in 8 patients (13.3%), including interstitial pneumonia (n = 2), skin disorders (n = 2), reactivated hepatitis B (n = 1), and fever of unknown origin (n = 3). CONCLUSION: Preliminary data suggest that CNI-free immunosuppression using everolimus is safe, with excellent efficacy in maintenance heart transplant recipients. Arterial hypertension and renal function improved significantly. CNI-induced side effects such as tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved in most patients. PMID- 17346628 TI - Basiliximab and rabbit anti-thymocyte globulin for prophylaxis of acute rejection after heart transplantation: a non-inferiority trial. AB - BACKGROUND: Induction of immunosuppression with antibodies after heart transplantation decreases early acute rejection rate compared with placebo. We tested the non-inferiority of basiliximab vs rabbit anti-thymocyte globulin (RATG) on the incidence of acute rejection 6 months after transplantation. METHODS: From July 2002 to April 2004, 35 patients were enrolled in a multicenter, parallel group, open-label, non-inferiority trial. Patients were randomized to receive induction treatment with basiliximab (20 mg on Day 0 and 4) or RATG (125 mg on Day 0, 1, and 2). Standard maintenance therapy with cyclosporine, mycophenolate mofetil, and prednisone was used. RESULTS: Seventeen patients (aged 54 +/- 9 years old) received basiliximab, and 18 patients (aged 54 +/- 12 years old) received RATG. The freedom rate of rejection at 6 months (grade 3A or more) averaged 65% (11/17) with basiliximab and 83% (15/18) with RATG. The upper limit of the 1-sided 90% confidence interval for the difference RATG basiliximab was 37.2%, exceeding the 22.5% non-inferiority margin. CD3 and CD4 levels were higher (p < 0.0001 for both), whereas CD25/CD4 and CD25/CD8 levels were lower (p < 0.0001 and p = 0.0462, respectively) in patients treated with basiliximab. One of the 14 basiliximab patients showed detectable cytomegalovirus viral load during the first 3 months after transplantation, whereas cytomegalovirus was detected by quantitative polymerase chain reaction in the plasma of 5 of the 13 RATG patients (p = 0.0505). CONCLUSION: Non-inferiority of basiliximab treatment for prophylaxis of acute rejection after heart transplantation could not be shown. RATG administration is associated with a higher rate of asymptomatic cytomegalovirus viral load detection in the plasma. PMID- 17346629 TI - Statin therapy associated with a reduced risk of chronic renal failure after cardiac transplantation. AB - BACKGROUND: Chronic renal failure (CRF) after heart transplantation is common, although risk factors for its development and potential preventive interventions are not well established. METHODS: In this study we retrospectively assessed the cumulative incidence of CRF and identified independent predictors of CRF in heart transplant recipients between August 1986 and January 2003. RESULTS: Among the 218 patients included in the analysis, the cumulative incidence of CRF was 4.5% at 5 years, and 19.6% at 10 years after transplant. Multivariate Cox modeling revealed that diabetes mellitus prior to transplant was associated with an increased risk of CRF (hazards ratio [HR] 7.11, p < 0.01), whereas factors associated with a reduced risk of CRF included a pre-transplant creatinine clearance > or = 60 ml/min/1.73 m2 (HR 0.30, p = 0.01) and treatment with a statin after transplant (HR 0.25, p < 0.01). Patients who developed CRF after transplant were at higher risk of death (HR 8.5, p < 0.01). CONCLUSIONS: CRF is common after cardiac transplantation and is associated with substantial mortality. The reduced risk of CRF observed with statin therapy warrants prospective study, with particular emphasis on the mechanisms of progression to CRF in this population. PMID- 17346630 TI - In vivo optical bioluminescence imaging of collagen-supported cardiac cell grafts. AB - BACKGROUND: Histology-based survival assessment of cell grafts does not allow for in vivo follow-up. In this study we introduce two new experimental models for longitudinal in vivo survival studies of cardiac cell grafts using optical bioluminescence imaging. METHODS: H9c2 cardiomyoblasts expressing both firefly luciferase (fluc) and green fluorescent protein (GFP) reporter genes were implanted into Lewis rats. In Model 1, H9c2-fluc-IRES-GFP cells (0.5 x 10(6)) were implanted into a cryoinjured abdominal wall muscle. Cells were injected using either liquid collagen (Matrigel [MG]) or phosphate-buffered saline (PBS) suspension. Cell survival was evaluated in vivo using bioluminescence imaging on days 1, 5 and 10 post-operatively. In model 2, rats underwent ligation of the left anterior descending (LAD) artery. The donor hearts were harvested, and the infarcted region was restored ex situ using 1 x 10(6) H9c2-fluc-IRES-GFP cells seeded in collagen matrix (Gelfoam [GF]) or suspended in PBS (n = 8/group). Hearts were then transplanted into the abdomen of syngeneic recipients. Optical bioluminescence imaging was performed on Days 1, 5, 8 and 14 post-operatively. After 4 weeks, immunohistologic studies were performed. RESULTS: For model 1, at day 5, bioluminescence signals were markedly higher for the H9c2/MG group (449 +/ 129 photons/second x 10(3)) compared with the H9c2/PBS group (137 +/- 82 photons/second x 10(3)) (p < 0.05). For model 2, bioluminescence signals were significantly (p < 0.04) higher in the H9c2/GF group compared with plain cell injection on days 5 (534 +/- 115 vs 219 +/- 34) and 8 (274 +/- 34 vs 180 +/- 23). Data were in accordance with GFP immunohistology. CONCLUSIONS: Optical bioluminescence is a powerful method for assessment of cardiac cell graft survival in vivo. Collagen matrices support early survival of cardiomyoblasts after transplantation into injured musculature. PMID- 17346631 TI - Treatment of hypercholesterolemia with ezetimibe in cardiac transplant recipients. AB - The purpose of this study was to examine the efficacy and tolerability of ezetimibe in cardiac transplant recipients who were intolerant of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors (statins) or unable to reach target lipid levels with statin therapy. After treatment with ezetimibe (n = 16), mean total and low-density lipoprotein cholesterol levels decreased significantly (228 +/- 40 mg/dl to 197 +/- 48 mg/dl, p = 0.003; and 149 +/- 34 mg/dl to 117 +/- 39 mg/dl, p < 0.001, respectively). One patient required a reduction in ezetimibe dose owing to myalgias; no other adverse events occurred. This initial experience indicates that ezetimibe is well tolerated in cardiac transplant recipients and is effective in reducing total and low-density lipoprotein cholesterol levels. PMID- 17346632 TI - Primary cryptococcal cellulitis in a lung transplant recipient. AB - In organ transplant recipients there remains controversy whether cutaneous cryptococcal infection represents a primary infection or a manifestation of disseminated cryptococcosis. We describe a lung transplant patient who developed primary cryptococcal cellulitis in the immediate post-operative period. At presentation, disseminated disease was excluded. The patient was treated with liposomal amphotericin B and fluconazole and, in addition, a surgical debridement was performed. Shortly afterwards, computed tomography revealed dissemination to the brain. The patient died of cerebral edema. As there was no involvement of the central nervous system at presentation, we believe that cryptococcal cellulitis was the primary site of infection and origin of dissemination. In this study we review cryptococcosis, which should always be considered in the differential diagnosis of cellulitis in transplant recipients. PMID- 17346633 TI - Challenging venous reconstruction and heart transplantation in a patient with viscero-atrial situs inversus and complex congenital heart disease with Fontan circulation. AB - Heart transplantation represents a valuable therapeutic option for patients with congenital heart disease and end-stage heart failure. We report the case of a 15 year-old patient with situs inversus and additional complex congenital malformations of the heart who underwent several previous palliative operations. Orthotopic cardiac transplantation with several technical modifications was performed successfully. At 18 months post-operatively the patient is free from rejection and doing well in New York Heart Association (NYHA) Class I status. PMID- 17346634 TI - X-linked cardiomyopathy presenting as contracted endocardial fibroelastosis. AB - We report a case of familial contracted endocardial fibroelastosis (EFE) in a young boy presenting at 14 months of age with severe heart failure. A previous echocardiogram showed normal left ventricular (LV) size and systolic function. The family history was suggestive of X-linked cardiomyopathy. These findings are assessed in light of earlier reports of contracted EFE. PMID- 17346635 TI - Acute sirolimus pulmonary toxicity in an infant heart transplant recipient: case report and literature review. AB - Sirolimus-associated pulmonary disease should be considered in the differential diagnosis of acute respiratory distress syndrome in transplant recipients receiving this drug. It represents a rare, potentially lethal, and yet reversible adverse effect. We report the case an infant who presented with acute respiratory distress 57 days after heart transplantation 3 days after starting sirolimus. The acute presentation and prompt resolution after discontinuation of this drug suggest a direct toxic effect to the lungs. To our knowledge, this is the first published pediatric description of this syndrome after heart transplantation. PMID- 17346636 TI - Cardiac transplantation in patients with anti-phospholipid antibodies. AB - Patients with severe heart failure are known to have an increased incidence of thromboembolic events and frequently have a visible thrombus in the left ventricle. Thromboemboli in heart failure patients are usually attributed to the underlying heart failure, and alternative etiologies for thrombus formation are rarely sought. However, anti-phospholipid antibodies and other inherited or acquired clotting abnormalities may contribute to hypercoagulability in heart failure patients and can lead to a persistent high risk for clotting, even after heart transplantation has corrected the underlying heart failure. We report outcomes with heart transplantation in 3 young patients with anti-phospholipid antibodies and a history of pre-heart transplantation thromboembolic events, and demonstrate the importance of post-heart transplantation anti-coagulation in these patients. PMID- 17346637 TI - Does tricuspid annular plane systolic excursion (TAPSE) or systolic velocity (Sm) allow an easier determination of right ventricular function after heart transplantation? PMID- 17346638 TI - Elective conversion from CellCept to Myfortic under control of mycophenolic acid concentration in stable heart transplant recipients. PMID- 17346640 TI - Is this child in supraventricular tachycardia? PMID- 17346641 TI - A chest pain patient refuses transport. PMID- 17346642 TI - Sampling methods: selecting your subjects. PMID- 17346645 TI - In search of a benchmark: a proposed standard efficiency rating for air medical billing services. PMID- 17346646 TI - Saving grace. PMID- 17346647 TI - A survey of adherence to community-generated safety guidelines in rotor-wing air medical programs. AB - INTRODUCTION: Operational safety, both crash prevention and improved crash survival, is a central concern in the air medical community. Professional organizations have published operational safety guidelines, but the extent to which those guidelines are followed is unclear. We report the results of a survey of adherence with selected safe practice recommendations. METHODS: An anonymous survey of adherence with 8 individual and 11 program safety guidelines was distributed to flight team members at 10 Association of Air Medical Services member rotor-wing air medical programs selected by stratified random sample to ensure geographic diversity. Descriptive statistics are reported and relationships are evaluated with the chi-square test. The sample size provided 80% power at a .05 significance level for the comparisons. RESULTS: Data were analyzed from 126 of the 200 surveys distributed. Adherence with program-wide safety behaviors ranged from 41.3% (complete a pre-departure checklist) to 99.2% (program has an annual safety review). Adherence to individual behaviors ranged from 15.1% (wear fire-resistant gloves) to 99.2% (wear seatbelts and shoulder harnesses on approach and departure). There was 100% adherence to wearing helmets by the respondents whose program provided a helmet at no cost to the staff member. There were no associations between job description and any individual behavior. Hospital-operated programs were less likely to have a daily briefing (P < .05), less likely to have a written policy allowing flight refusal for fatigue (P < .01), and tended toward lower rates of having a written policy allowing flight refusal for fatigue (P = .07). Non-hospital-operated programs were less likely to provide helmets (P < .001), to operate in an airframe with a clear headstrike area (P < .001), and to wear long-sleeved fire-resistant flight suits (P = .01). CONCLUSION: Both organizational and individual adherence to community safety recommendations are variable and not universal. There is variability by operational models. PMID- 17346648 TI - Should we fly or drive? The use of a computer-based system (ANTSS) for resource utilization. AB - Objective methods are needed to accurately allocate limited resources for the transport of critically ill patients. This manuscript presents the implementation of a novel internet-based charting system that employs a background physiologic acuity scoring system. Based on this score, the system, named ANTSS (Assessment of Neonates for Transport Scoring Software), assigns a color code to the patient (red, yellow, green). The system, based on the color coding, recommends a particular transport vehicle. ANTSS was initially evaluated using a survey to assess the systems effect on workload and the usefulness of the physiologic scoring. The survey was administered to the physicians who input the initial information. An objective count of the fields entered by the physicians using our older handwritten method was compared with the number of fields completed using ANTSS. Finally, a second survey was administered to members of the transport team to evaluate whether ANTSS-generated charts provided improved patient information to the end users of the information. The results from the surveys demonstrate that ANTSS improves the patient information provided to the transport team, provides the physician with useful objective information concerning the mode of transport, and increases the amount of completed fields in the transport record. PMID- 17346649 TI - Turkish Hemapheresis Society activity for 2005. PMID- 17346650 TI - Hyperthyroidism in molar pregnancy: rapid preoperative preparation by plasmapheresis and complete improvement after evacuation. AB - Human chorionic gonadotropin bears structural homology to pituitary thyrotropin. The extremely elevated levels of human chorionic gonadotropin in patients with molar pregnancy or other trophoblastic diseases can lead to hyperthyroidism. We describe a patient with molar pregnancy who had secondary hyperthyroidism prepared rapidly by plasmapheresis for surgery. The clinical picture improved dramatically after the first plasmapheresis. Three subsequent plasmapheresis provided a 75.1% decrease in serum free T3 concentrations and 63.9% free T4 concentrations and recovery after evacuation. This is the first use of plasmapheresis in rapid preparation of a patient who had secondary hyperthyroidism due to molar pregnancy. PMID- 17346653 TI - Association between family variables and Mexican American children's dietary behaviors. AB - OBJECTIVE: To examine the association between family variables and children's diets. DESIGN: Cross-sectional study with households sampled using random-digit dialing. Children completed a one-time, self-administered survey, and mothers participated in a face-to-face structured interview. SETTING: Data collection occurred in southern San Diego County on the U.S.-Mexico border. PARTICIPANTS: One hundred sixty-seven Mexican American children between 8 and 18 years of age and their mothers. MAIN OUTCOME MEASURES: Diet: number of snacks, candies and sweets, and sodas consumed daily; dietary fat and fiber; and money spent weekly on fast food and snacks. Family variables: household size, family support for healthful eating, number of meals eaten together, availability of fast food in the home, food ads seen on television, and parent purchasing food products that children saw advertised on television. DATA ANALYSES: Regression analyses were used to examine the independent contributions of family variables on dietary intake. Statistical significance was set at P < .05. RESULTS: Greater family support for healthful eating was associated with fewer snacks and more fiber consumed. Children of parents who purchased food products that their children had seen advertised on television reported consuming more snacks and more fat, and they spent more money on fast food and snacks. CONCLUSIONS AND IMPLICATIONS: Family-based interventions are needed to moderate the potential influence of television-advertised food products on children's requests for these food products. PMID- 17346654 TI - Effects of a Web-based food portion training program on food portion estimation. AB - OBJECTIVE: Assess the effects of a prototype computerized food portion tutorial (CFPT). DESIGN: Participants were randomly assigned to estimate portion sizes for selected food items either prior to or following CFPT training (between groups), and those estimating before CFPT training re-estimated portions after training (within groups). SETTING: Research offices. PARTICIPANTS: Seventy-six adult participants without dietary restrictions. INTERVENTION: The CFPT is a Web-based food portion training program that displays varied portions of 23 food items with user-controllable reference objects and viewing angles. MAIN OUTCOME MEASURES: Estimated vs. weighed portions of food items selected for a meal. ANALYSIS: Nonparametric tests were performed on estimated vs. weighed portion differences and on accuracy ratios between and within groups. RESULTS: A significant difference was found between conditions, both within and between groups, on the discrepancy between estimated and weighed portions for a number of the food items. Training exposure, however, resulted primarily in a shift from underestimation to overestimation, not more accurate estimation. IMPLICATIONS FOR RESEARCH AND PRACTICE: The CFPT produced a significant impact on food portion estimation but appeared to sensitize participants to underestimation errors, leading to overestimation errors. Computerization of food portion training programs holds promise for providing cost-efficient portion estimation training but requires further development and evaluation before being considered for clinical use. PMID- 17346655 TI - Food supply adequacy in the Lower Mississippi Delta. AB - OBJECTIVE: To assess food supply adequacy within 3 food store types in the Lower Mississippi Delta. DESIGN: Regional food store survey to determine availability and quality of 102 food items in 62 supermarkets, 77 small/medium stores, and 86 convenience stores. SETTING: Lower Mississippi Delta region of the United States. PARTICIPANTS: 225 food stores in 18 counties. MAIN OUTCOME MEASURES: Percentage of Thrifty Food Plan (TFP) food items available and quality ratings of 6 food sections across store types. RESULTS: On average, supermarkets carried 96% of the items that compose the TFP. Mean percentage of TFP carried in small/medium stores was 50%. Convenience stores carried 28% of the TFP items. Supermarkets had higher overall quality ratings and quality ratings for fresh and frozen foods compared to small/medium and convenience stores (P<.01). IMPLICATIONS FOR RESEARCH AND PRACTICE: Although supermarkets carried a large percentage of items surveyed, the number of supermarkets in this region is limited. Community residents with limited transportation to reach supermarkets may experience limited food supply adequacy. Therefore, community-based nutrition interventions should include partnerships with small/medium food retailers while trying to impact residents' food choices within those stores. PMID- 17346656 TI - Differences between parents' and adolescents' perceptions of family food rules and availability. AB - OBJECTIVE: To test the hypotheses that adolescents have different perceptions of family-environmental factors than do their parents, and that dietary intake of adolescents is more highly associated with the adolescent's own perceptions than those of their parents. DESIGN: Data from self-administered questionnaires were used. PARTICIPANTS: Five-hundred two students aged 12 to 14 years, and one of each student's parents. MAIN OUTCOME MEASURES: Two types of family-environmental factors (ie, family food rules and home availability and accessibility of food) for 3 self-reported dietary behaviors (ie, fruit, snack, and breakfast intake). ANALYSIS: Unpaired t tests, chi-square tests, percentage (gross) disagreement, standardized regression coefficients, and linear regression analyses. RESULTS: For most rules and most perceptions of availability and accessibility, considerable disagreement was found between parents and students. Self-reported intake of fruit and snacks was more highly associated with student measures, but breakfast intake was more highly associated with parent measures of rules and availability. IMPLICATIONS FOR RESEARCH AND PRACTICE: The findings might explain mixed results on the associations between family-environmental factors and children's dietary intake that were found in earlier studies. Researchers need to be aware that in studies into family-environmental determinants of dietary habits using self-reports, the results are possibly influenced by whether the data were reported by parents or by children. PMID- 17346657 TI - Whole-grain intake is associated with body mass index in college students. AB - OBJECTIVE: To measure whole-grain intake in college students and determine the association with body mass index (BMI). DESIGN: Cross-sectional convenience sample of college students enrolled in an introductory nutrition course. SETTING: Large state university. PARTICIPANTS: 159 college students, mean age: 19.9. MAIN OUTCOME MEASURES: Intake of whole grains, refined grains, calories, and fiber from food records; BMI determined from height and weight measurements. ANALYSIS: Analysis of variance with linear contrasts; participants grouped by BMI category (P<.05). RESULTS: Average intake of cereal grains was 5.4 servings per day, of which whole-grain intake accounted for an average of 0.7 servings per day. Whole grain intake was significantly higher in normal weight students than in overweight and obese students (based on BMI). CONCLUSIONS AND IMPLICATIONS: The low intake of whole grains in this population of college students indicates the need for interventions aiming to increase whole-grain intake to the recommended minimum of 3 servings per day. College students who are concerned about their body weight may be motivated to increase their intake of whole-grain foods; however, their intake of whole grains is likely to be influenced by the availability of these food items in campus dining halls and other locations around the college campus. PMID- 17346658 TI - Status and goals of local school wellness policies in Virginia: a response to the child nutrition and WIC Reauthorization Act of 2004. AB - By fall 2006 each school division participating in the National School Lunch Program was mandated to establish a local wellness policy. The study objective was to assess schools' plans for the policy, including goals for food, nutrition education, and physical activity and evaluation. Surveys were administered to 132 School Health Advisory Board coordinators in Virginia in early 2006; 92 (69.7%) responded. The findings highlight gaps toward meeting minimum requirements for the policy and give guidance on how nutrition educators and researchers can provide expertise to optimize the policy and document progress and impacts on children's health related to the policy. PMID- 17346659 TI - Use of actors as simulated patients in nutritional counseling. PMID- 17346660 TI - Picking the nutrition facts from the fads: an internet-based tutorial. PMID- 17346661 TI - An internet-based assessment tool for food choices and physical activity behaviors. PMID- 17346662 TI - Study limitations reveal challenging nature of nutrition education research. PMID- 17346663 TI - High yield, purity and activity of soluble recombinant Bacteroides thetaiotaomicron GST-heparinase I from Escherichia coli. AB - Heparinase I from Flavobacterium heparinum, a source of diverse polysaccharidases, suffers from low yields, insufficient purity for structural studies and insolubility when expressed as a recombinant product in Escherichia coli that is devoid of glycosaminoglycan polysaccharidases. In this study, cDNA coding for the orthologue of F. heparinum heparinase I was constructed from genomic information from the mammalian gut symbiont Bacteroides thetaiotaomicron and expressed in E. coli as a fusion protein with GST at the N-terminus. This resulted in high yield (30 mg/g dry bacteria) of soluble product and facilitated one-step affinity purification to homogeneity. Purified heparinase I bearing the GST fusion exhibited a K(m) of 2.3 microM and V(max) of 42.7 micromol/min with a specific activity of 164 U/mg with heparin (average 12,000 Da) as substrate. The results indicate a 2-fold improvement in yield, specific activity and affinity for heparin as substrate over previous reports. The data suggest that the heparinase I from the gut symbiont exhibits a higher intrinsic affinity for heparin than that from F. heparinum. The purified GST fusion enzyme exhibited a requirement for Ca(2+) and a pH optimum between 6.7 and 7.3 that was similar to the enzyme freed of the N-terminal GST portion. Our study revealed that catalytic activity of heparinase I requires a reducing environment. The GST facilitated immobilization of heparinase I in solid phase either for clinical purposes or for structural studies in absence of interference by contaminating polysaccharidases. PMID- 17346664 TI - PPARbeta/delta activation inhibits angiotensin II-induced collagen type I expression in rat cardiac fibroblasts. AB - Peroxisome proliferator-activated receptors (PPARalpha, beta/delta and gamma) are nuclear receptors and PPARgamma activation was previously reported to inhibit collagen expression in the heart, but whether PPARbeta/delta also regulates collagen expression in the heart remains unclear. In this study, we investigated the effect of PPARbeta/delta activation on angiotensin II (Ang II)-induced collagen type I expression in adult rat cardiac fibroblasts. The results showed that PPARbeta/delta was expressed at the moderate level in cardiac fibroblasts. GW501516, a selective PPARbeta/delta agonist, depressed Ang II-stimulated collagen type I expression and collagen synthesis in cardiac fibroblasts in a concentration-dependent manner. Furthermore, these inhibitory effects of GW501516 were completely reversed by the knockdown of PPARbeta/delta via RNA interference. In summary, we find that PPARbeta/delta is present in cardiac fibroblasts and PPARbeta/delta activation inhibits Ang II-induced collagen type I expression at least in part via decreasing collagen synthesis. PPARbeta/delta may be a promising therapeutic target for myocardial fibrosis. PMID- 17346665 TI - Crystal structure of the vitamin D nuclear receptor ligand binding domain in complex with a locked side chain analog of calcitriol. AB - The crystal structures of vitamin D nuclear receptor (VDR) have revealed that all compounds are anchored by the same residues to the ligand binding pocket (LBP). Based on this observation, a synthetic analog with a locked side chain (21-nor calcitriol-20(22),23-diyne) has been synthesized in order to gain in entropy energy with a predefined active side chain conformation. The crystal structure of VDR LBD bound to this locked side chain analogue while confirming the docking provides a structural basis for the activity of this compound. PMID- 17346666 TI - Organisation of Photosystem I and Photosystem II in red alga Cyanidium caldarium: encounter of cyanobacterial and higher plant concepts. AB - Structure and organisation of Photosystem I and Photosystem II isolated from red alga Cyanidium caldarium was determined by electron microscopy and single particle image analysis. The overall structure of Photosystem II was found to be similar to that known from cyanobacteria. The location of additional 20 kDa (PsbQ') extrinsic protein that forms part of the oxygen evolving complex was suggested to be in the vicinity of cytochrome c-550 (PsbV) and the 12 kDa (PsbU) protein. Photosystem I was determined as a monomeric unit consisting of PsaA/B core complex with varying amounts of antenna subunits attached. The number of these subunits was seen to be dependent on the light conditions used during cell cultivation. The role of PsaH and PsaG proteins of Photosystem I in trimerisation and antennae complexes binding is discussed. PMID- 17346667 TI - Carvedilol inhibits mitochondrial complex I and induces resistance to H2O2 mediated oxidative insult in H9C2 myocardial cells. AB - Carvedilol, a beta-adrenoreceptor antagonist with strong antioxidant activity, produces a high degree of cardioprotection in a variety of experimental models of ischemic cardiac injury. Although growing evidences suggest specific effects on mitochondrial metabolism, how carvedilol would exert its overall activity has not been completely disclosed. In the present work we have investigated the impact of carvedilol-treatment on mitochondrial bioenergetic functions and ROS metabolism in H9C2 cells. This analysis has revealed a dose-dependent decrease in respiratory fluxes by NAD-dependent substrates associated with a consistent decline of mitochondrial complex I activity. These changes were associated with an increase in mitochondrial H(2)O(2) production, total glutathione and protein thiols content. To evaluate the antioxidant activity of carvedilol, the effect of the exposure of control and carvedilol-pretreated H9C2 cells to H(2)O(2) were investigated. The H(2)O(2)-mediated oxidative insult resulted in a significant decrease of mitochondrial respiration, glutathione and protein thiol content and in an increased level of GSSG. These changes were prevented by carvedilol pretreatment. A similar protective effect on mitochondrial respiration could be obtained by pre-treatment of the cells with a sub-saturating amount of rotenone, a complex I inhibitor. We therefore suggest that carvedilol exerts its protective antioxidant action both by a direct antioxidant effect and by a preconditioning like mechanism, via inhibition of mitochondrial complex I. PMID- 17346668 TI - Mapping of the structural determinants of artificial and biological membrane damaging activities of a Lys49 phospholipase A2 by scanning alanine mutagenesis. AB - Scanning alanine mutagenesis has been used to study the structural determinants of several activities of bothropstoxin-I (BthTx-I), a lysine 49 Phospholipases A(2) from the venom of Bothrops jararacussu. A total of 31 mutants were generated in the interfacial recognition site and C-terminal loop regions of the protein. The effects of mutagenesis on the in vivo myotoxic activity, the cytolytic activity against cultured C2C12 myoblasts, the bactericidal activity, and the Ca(2+)-independent membrane damaging activity against liposome membranes were compared. Residues 116-119 and 122-125 in the C-terminal loop region are structural determinants for these activities, indicating that membrane permeabilization by the BthTx-I is an important general property in all the measured effects. The structural determinants of myotoxicity and myoblast membrane permeabilization are highly correlated, demonstrating that cultured C2C12 myoblasts are a good model for the myotoxic effect. However, comparison of the structural determinants for all activities revealed several differences in the structural determinants between the effects against myoblast and bacterial membranes, and further differences when compared to the liposome membrane damaging effect. These membrane dependent effects are interpreted to be the consequence of differences in the activation of the membrane bound form of the protein on biological and artificial membranes. PMID- 17346669 TI - In vivo suppression of mafA mRNA with siRNA and analysis of the resulting alteration of the gene expression profile in mouse pancreas by the microarray method. AB - Maf is a family of transcription factor proteins that is characterized by a typical bZip structure, and one of the large mafs, mafA is a strong transactivator of insulin. To explore the role of mafA in the pancreas, we modified the mafA mRNA level in vivo in mice by the RNA interference (siRNA) technique and analyzed the resulting alteration of the expressed gene profile with a microarray system. The mafA expression level in siRNA-treated mice was reduced approximately 60% compared with control-siRNA-treated animals. Microarray analysis revealed changes in the expression level of several genes in the siRNA treated mice, with prominent down-regulated expression of the genes encoding insulin, glucagon, and adipocytokines, suggesting possible role of mafA in the pathophysiological states of impaired metabolic responses or inflammatory reactions. PMID- 17346670 TI - Relative levels of RNA polII subunits differentially affect starvation response in budding yeast. AB - The Rpb4/7 subcomplex of RNA polymerase II in Saccharomyces cerevisiae is known to play an important role in stress response and stress survival. These two proteins perform overlapping functions ensuring an appropriate cellular response through transcriptional regulation of gene expression. Rpb4 and Rpb7 also perform many cellular functions either together or independent of one another. Here, we show that Rpb4 and Rpb7 differently affect during the nutritional starvation response pathways of sporulation and pseudohyphae formation. Rpb4 enhances the cells' proficiency to sporulate but suppresses pseudohyphal growth. On the other hand, Rpb7 promotes pseudohyphal growth and suppresses sporulation in a dose dependent manner. We present a model whereby the stoichiometry of Rpb4 and Rpb7 and their relative levels in the cell play a switch like role in establishing either sporulation or pseudohyphal gene expression. PMID- 17346671 TI - The chicken host peptides, gallinacins 4, 7, and 9 have antimicrobial activity against Salmonella serovars. AB - The gallinacin genes clustered on chromosome 3 of the chicken (Gallus gallus domesticus) genome encode a group of cationic antimicrobial peptides characteristic of the beta-defensins. In this study, gallinacins 4, 7, and 9, all predicted to contain the conserved pattern of cysteines typical of beta-defensins but differing in their charge and hydrophobicity, were characterised for their in vivo gene expression patterns and in vitro antimicrobial activities against Salmonella serovars. Reverse-transcription PCR analyses of chicken epithelial tissues indicated gallinacin (Gal) 7 expression to be ubiquitous while Gal 4 and Gal 9 expression appeared localized to specific epithelial tissues including the ovary, trachea, and lung, respectively. In addition Gal 7, but neither Gal 4 nor Gal 9, expression was identified in tissues taken from the non-domesticated bird species, Parus caeruleus, Larus argentatus, and Columba palambus. Analysis of Gal 7 expression in chickens in response to an oral challenge with either Salmonella enterica serovar Typhimurium SL1344 or Salmonella enteriditis indicated no significant increase in small intestinal Gal 7 mRNA expression although a significant increase (p <0.05) was detected in the liver, suggesting that, in response to Salmonella infection Gal 7 expression is inducible in the liver. Neither Gal 4 nor Gal 9 expression was induced in the chicken small intestine in response to the oral Salmonella infection. The antimicrobial capabilities of Gals 4, 7, and 9 against Salmonella serovars including S. typhimurium SL1344 and S. enteriditis were investigated in vitro using recombinant His-tagged peptides and a time-kill assay. The antimicrobial activity data indicated the potency of the recombinant gallinacins against the Salmonella serovars to be in the order Gal 9> or=4>7, and provided evidence for the synergistic interaction of Gals 7 and 9 against S. enteriditis. These results support in silico data that Gals 4, 7, and 9 are part of the innate defences of the chicken and function in microbial killing activities. PMID- 17346672 TI - Lateral diffusion of TGF-beta type I receptor studied by single-molecule imaging. AB - In this report, we investigated the lateral diffusion of transforming growth factor beta (TGF-beta) type I receptor (TbetaRI) in living cells by imaging and tracking individual green fluorescent protein tagged TbetaRI on the cell membrane. We found that when co-expressed with TGF-beta type II receptor (TbetaRII), the mobility of TbetaRI decreased significantly after TGF-beta1 stimulation. However, in the cells that had been depleted of cholesterol with Nystatin or methyl-beta-cyclodextrin, the diffusion rate of TbetaRI was not changed by TGF-beta1 treatment. Our observations suggest that membrane lipid rafts provide an environment that facilitates the association of TbetaRI and TbetaRII for cell signaling. PMID- 17346673 TI - Activation of MAPK in fibroblasts by Treponema denticola major outer sheath protein. AB - The major outer sheath protein (Msp) of Treponema denticola induces Ca(2+) entry and actin reorganization in cultured fibroblasts, but the pathways by which Msp mediates these responses are not yet defined. We considered that Msp may activate protein kinases as a stress response that precedes actin remodelling. Phospho kinase screens showed that Msp induced phosphorylation of multiple kinases in pathways that respond to extracellular agonists and regulate actin assembly. 34 kinases were significantly activated, including p38 and ERK 1/2. Accordingly, the expression and phosphorylation of p38 and ERK 1/2 in whole cell lysates were measured by immunoblotting and densitometry. Both kinases responded in a dose- and time-dependent manner to Msp exposure, were inhibited by SB202190 and U1026, respectively, and were unaffected by extracellular Ca(2+). These data indicate that T. denticola Msp may exert transient stress on fibroblasts through activation of MAP kinase pathways. PMID- 17346674 TI - Isolation and genetic analysis of human origin H1N1 and H3N2 influenza viruses from pigs in China. AB - Influenza A viruses of subtypes H1N1 and H3N2 have been reported widely in pigs, associated with clinical disease. These mainly include classical swine H1N1, avian-like H1N1, and human-like or avian-like H3N2 viruses. From 2005 to 2006, we carried out swine influenza virus surveillance in eight provinces of China. Here we report, for the first time, the isolation and genetic analysis of a human-like influenza H1N1 virus from a pig in a farm of Guangdong province of southern China, a host suspected to generate new pandemic strains through genetic reassortment. Each of the eight gene segments is of human origin. Phylogenetic analysis indicates that these genes form a human lineage, suggesting that this virus is the descendant of recent human H1N1 influenza viruses. In addition, four swine H3N2 viruses were also isolated. The three H3N2 viruses from Guangdong province are descendants of recent human viruses, while an H3N2 virus from Heilongjiang province derives from early human viruses. Isolation and genetic analysis of human H1N1 and H3N2 influenza viruses from pigs in China provides further evidence about the interspecies transmission of human influenza viruses to pigs and emphasizes the importance of reinforcing swine influenza virus surveillance. PMID- 17346675 TI - N-methyltetrahydro-beta-carboline analogs of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) neurotoxin are oxidized to neurotoxic beta-carbolinium cations by heme peroxidases. AB - 2-Methyl-1,2,3,4-tetrahydro-beta-carboline (2-Me-THbetaC) and 2,9-dimethyl 1,2,3,4-tetrahydro-beta-carboline (2,9-diMe-THbetaC) are naturally occurring analogs of the Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), whereas their corresponding aromatic 2-methyl-beta carbolinium cations resemble 1-methyl-4-phenylpyridinium (MPP(+)) and are considered potential toxins involved in Parkinson's disease (PD). To become toxicants, 2-methyltetrahydro-beta-carbolines need to be oxidized (aromatized) by human metabolic enzymes to pyridinium-like (beta-carbolinium) cations as occur with MPTP/MPP(+) model. In contrast to MPTP, human MAO-A or -B were not able to oxidize 2-Me-THbetaC to pyridinium-like cations. Neither, cytochrome P-450 2D6 or a mixture of six P450 enzymes carried out this oxidation in a significant manner. However, 2-Me-THbetaC and 2,9-diMe-THbetaC were efficiently oxidized by horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO) to 2-methyl-3,4-dihydro-beta-carbolinium cations (2-Me-DHbetaC(+), 2,9-diMe DHbetaC(+)) as the main products, and detectable amount of 2-methyl-beta carbolinium cations (2-Me-betaC(+), 2,9-diMe-betaC(+)). The apparent kinetic parameters (k(cat), k(4)) were similar for HRP and LPO and higher for MPO. Peroxidase inhibitors (hydroxylamine, sodium azide, and ascorbic acid) highly reduced or abolished this oxidation. Although MPTP was not oxidized by peroxidases; its intermediate metabolite 1-methyl-4-phenyl-2,3-dihydropyridinium cation (MPDP(+)) was efficiently oxidized to MPP(+) by heme peroxidases. It is concluded that heme peroxidases could be key catalysts responsible for the aromatization (bioactivation) of endogenous and naturally occurring N methyltetrahydro-beta-carbolines and related protoxins to toxic pyridinium-like cations resembling MPP(+), suggesting a role for these enzymes in toxicological and neurotoxicological processes. PMID- 17346676 TI - Formation of polyamine-modified peptides during protein digestion. AB - The effect of polyamines on the digestion of proteins by serine proteases was examined. Based on the mechanism of action of serine proteases, it was anticipated that nucleophilic functionalities such as amino groups in polyamine, rather than hydroxyl ions, would react with peptide bonds during the hydrolysis process. If this were the case, polyamine might be covalently linked to the C terminus of the product peptides during protein digestion. In order to test this hypothesis, hemoglobin was used as a model protein and was digested with trypsin in the presence of polyamine. The product peptides were separated, collected by HPLC, and analyzed by MALDI-TOF MS using post-source decay. The results showed that some peptides were indeed modified with polyamine at the C-terminus. PMID- 17346677 TI - HER-2/neu raises SHP-2, stops IFN-gamma anti-proliferation in bladder cancer. AB - Gene amplification or HER-2/neu protein overexpression signals a poor outcome for bladder cancer patients. We investigated the anti-proliferative effect of IFN gamma in HER-2/neu-transfected human bladder cancer cells (TCC-N5 and TCC-N10). The cells continued growing after IFN-gamma stimulation but did not activate the Janus kinase (Jak)/Stat pathway. We found Jak/Stat protein phosphatase in TCC-N5 and TCC-N10 cells with upregulated Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2). After the cells had been treated with AG825, a HER-2/neu specific inhibitor, SHP-2 expression declined, and Jak2/Stat1 reactivated. Similar results were reported in a mouse bladder cancer cell line, MBT2, with constitutive HER-2/neu overexpression. Further, AG825 pretreatment restored the anti-proliferation activity of IFN-gamma in TCC-N5 and TCC-N10 cells. Therefore, the suppression of IFN-gamma signaling in HER-2/neu-overexpressing bladder cancer cells might be due to SHP-2 upregulation. The regulation of SHP-2 by HER-2/neu provides a new target for blocking the HER-2/neu oncogenic pathway. PMID- 17346678 TI - Hum-mPLoc: an ensemble classifier for large-scale human protein subcellular location prediction by incorporating samples with multiple sites. AB - Proteins may simultaneously exist at, or move between, two or more different subcellular locations. Proteins with multiple locations or dynamic feature of this kind are particularly interesting because they may have some very special biological functions intriguing to investigators in both basic research and drug discovery. For instance, among the 6408 human protein entries that have experimentally observed subcellular location annotations in the Swiss-Prot database (version 50.7, released 19-Sept-2006), 973 ( approximately 15%) have multiple location sites. The number of total human protein entries (except those annotated with "fragment" or those with less than 50 amino acids) in the same database is 14,370, meaning a gap of (14,370-6408)=7962 entries for which no knowledge is available about their subcellular locations. Although one can use the computational approach to predict the desired information for the gap, so far all the existing methods for predicting human protein subcellular localization are limited in the case of single location site only. To overcome such a barrier, a new ensemble classifier, named Hum-mPLoc, was developed that can be used to deal with the case of multiple location sites as well. Hum-mPLoc is freely accessible to the public as a web server at http://202.120.37.186/bioinf/hum multi. Meanwhile, for the convenience of people working in the relevant areas, Hum-mPLoc has been used to identify all human protein entries in the Swiss-Prot database that do not have subcellular location annotations or are annotated as being uncertain. The large-scale results thus obtained have been deposited in a downloadable file prepared with Microsoft Excel and named "Tab_Hum-mPLoc.xls". This file is available at the same website and will be updated twice a year to include new entries of human proteins and reflect the continuous development of Hum-mPLoc. PMID- 17346679 TI - Spurious genetic associations. AB - BACKGROUND: Genetic association studies are widely used in biomedical research and yet only a minority of positive findings stand the test of replication. I explored the capacity of association studies to produce false positive findings and the impact of various definitions of replication. METHODS: Genetically realistic simulation data of a typical genotyping/analytic approach for 10 single nucleotide polymorphisms (SNPs) in COMT, a commonly studied candidate gene. RESULTS: Candidate gene studies like those simulated here are highly likely to produce one or more false positive findings at alpha < or = .05, the pattern of findings can often be "compelling" or "intriguing," and false positive findings propagate and confuse the literature unless the definition of replication is precise. CONCLUSIONS: Findings from single association studies constitute "tentative knowledge" and must be interpreted with exceptional caution. For the association method to function as intended, every statistical comparison must be tracked and reported, and integrated replication is essential. Precise replication (the same SNPs, phenotype, and direction of association) is required in the interpretation of multiple association studies. PMID- 17346681 TI - Effects of postnatal formaldehyde exposure on pyramidal cell number, volume of cell layer in hippocampus and hemisphere in the rat: a stereological study. AB - 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 pyramidal cells in the cornu ammonis (CA) of the hippocampus. Neonatal Wistar rats were exposed to 0 ppm (control group), 6 ppm and 12 ppm (high concentration group) of FA concentrations throughout the 30-day period following the birth by placing them for 6 h/day in a glass chamber containing FA vapor. Then, some of the animals from each FA-treated group were anesthetized and decapitated at the day 30, and the remaining ones were killed at the day 90. The brains were removed immediately and fixed in 10% neutral-buffered FA solution. The Cavalieri principle was used to determine the volumes of the CA and the entire cerebral hemisphere. The optical fractionator counting method was used to estimate the total number of pyramidal cells in the CA. The appearance of pyramidal cells was normal under light microscopy at both postnatal day (PND) 30 and PND 90 in all groups. There were concentration-related volume changes of CA at PND 30 and PND 90; low concentration of FA significantly increased, whereas high concentration decreased the volume of CA in comparison of the control at PND 30. Importantly, high concentration of FA at PND 90 increased the volume of CA in comparison of the low concentration but not with the control. Furthermore, low and high concentrations of FA decreased the volume of hemisphere at PND 30, whereas a reverse effect of these concentrations was observed at the hemisphere of PND 90 in comparison of the control. In both CA and cerebral hemisphere, an age-related volume decrease in both control and low/high concentration groups were found. On the other hand, there were significant age-related reductions in the total number of pyramidal cells at 90 days of age irrespective of the groups examined. Rats treated with high concentration FA were seen to have significantly fewer pyramidal cell neurons than either the animals treated with low concentration FA or control groups (p<0.01). These observations indicate that pyramidal cells in the hippocampus may be vulnerable to FA exposure during the early period of life. PMID- 17346680 TI - Metabolic and behavioral deficits following a routine surgical procedure in rats. AB - To test the hypothesis that functional metabolic deficits observed following surgical brain injury are associated with changes in cognitive performance in rodents, we performed serial imaging studies in parallel with behavioral measures in control animals and in animals with surgical implants. Memory function was assessed using the novel object recognition (NOR) test, administered 3 days prior to and 3, 7, 14 and 56 days after surgery. At each time point, general locomotion was also measured. Metabolic imaging with 18F-fluorodeoxyglucose ([18F]FDG) occurred 28 and 58 days after surgery. Animals with surgical implants performed significantly worse on tests of object recognition, while general locomotion was unaffected by the implant. There was a significant decrease in glucose uptake after surgery in most of the hemisphere ipsilateral to the implant relative to the contralateral hemisphere. At both time points, the most significant metabolic deficits occurred in the primary motor cortex (-25%; p<0.001), sensory cortex ( 15%, p<0.001) and frontal cortex (-12%; p<0.001). Ipsilateral areas further from the site of insertion became progressively worse, including the sensory cortex, dorsal striatum and thalamus. These data was supported by a voxel-based analysis of the PET data, which revealed again a unilateral decrease in [18F]FDG uptake that extended throughout the ipsilateral cortex and persisted for the duration of the 58-day study. Probe implantation in the striatum results in a widespread and long-lasting decline in cortical glucose metabolism together with a persistent, injury-related deficit in the performance of a cognitive (object recognition) task in rats. PMID- 17346682 TI - Cholecystokinin levels in the rat brain during the estrous cycle. AB - Cholecystokinin (CCK) is widely distributed in the brain, and its expression has been shown to be regulated by estrogen. In the present study we used radioimmunoassay to monitor CCK levels in rat brain during a normal estrous cycle. Compared to di-estrous and estrous, CCK-like immunoreactivity was significantly reduced in cingulate and frontal cortex, hippocampus, striatum and hypothalamus during pro-estrous, that is the phase with the highest plasma estradiol levels. These results provide further evidence that circulating steroid hormones in the female rat can influence expression of a brain peptide, in this case CCK, and primarily in the limbic system, which is interesting in the context that CCK has been associated with anxiety and depression in both animals and humans. PMID- 17346683 TI - Selective vulnerability of hippocampal NAAGergic neurons in experimental temporal lobe epilepsy. AB - The dipeptide N-acetylaspartylglutamate (NAAG) has been recently implicated in numerous neurological disorders. NAAG binds and stimulates group II metabotropic glutamate receptors producing a down-modulation of synaptic glutamate release. In the present immunohistochemical study, we compare the distribution of NAAG containing (NAAGergic) neurons between the hippocampus of control and chronic epileptic rats obtained with the pilocarpine model of temporal lobe epilepsy. In the hippocampal formation, NAAGergic neurons comprise a subpopulation of GABAergic neurons. Examination by light microscopy revealed a significant reduction of NAAG-immunoreactive neurons in CA3 stratum oriens (35.8%) and CA1 stratum oriens (78.87%), stratum pyramidale (40%), and stratum radiatum (56.6%). Similar loss of NAAGergic neurons was observed in the subiculum characterized by 71.82% and 77.53% reduction in the stratum oriens and radiatum, respectively, when compared with controls. NAAGergic neurons in CA2 and dentate gyrus were apparently resistant to seizure-related cell loss but appeared more complex and exhibited numerous NAAG-positive puncta. Our findings indicate a selective vulnerability of NAAGergic neurons in temporal lobe epilepsy. PMID- 17346684 TI - Early inhibition of TNFalpha increases 6-hydroxydopamine-induced striatal degeneration. AB - Evidence suggests that tumor necrosis factor alpha (TNF) is a leading cause of dopaminergic neuronal cell death. TNF also, however, has neuroprotective effects. Thus, TNF might have a dual role following injury: immediate release after injury is protective, whereas chronic increases are detrimental. In the present study, 6 hydroxydopamine was used to lesion the dorsal striatum in male Fisher 344 rats at 2 different time points. Group 1 received a daily injection of TNFalpha antisense oligodeoxyribonucleotide (ODN) or control on days 1 through 7 post-lesion. Group 2 received a daily injection of TNF antisense ODN or control on days 5 through 15 post-lesion. Rats were killed on the day following the last injection of TNF antisense ODN. Injection of TNF antisense ODN on days 1 through 7 increased the area of the tyrosine-hydroxylase-negative zone ipsilateral to the injection when compared to controls. In contrast, when inhibition of TNF was delayed, the area of tyrosine hydroxylase loss was significantly reduced. These findings suggest that TNF release is neuroprotective in the early stages of injury but becomes neurotoxic when chronically induced. PMID- 17346685 TI - A qualitative and quantitative analysis of skilled forelimb reaching impairment following intracerebral hemorrhage in rats. AB - The Montoya staircase test is commonly used to measure skilled forelimb reaching ability in a number of brain injury and disease models, but little has been done to characterize the precise nature of the impairments observed after stroke. The present study used slow motion video-recording to analyze staircase reaching performance both qualitatively and quantitatively, and to precisely determine the components of fine forelimb motor function that are disturbed in the collagenase model of hemorrhagic stroke. Male Sprague-Dawley rats were trained to reach for pellets in the staircase task, and subjected to either striatal hemorrhage induced by microinjections of bacterial collagenase or sham surgery. Reaching performance was recorded and examined before surgery, and 2 and 4 weeks later. Impaired animals made fewer attempts and retrieved less pellets than did shams, especially from the lower steps. Interestingly, impaired animals were less able to retrieve a pellet even when the forepaw made contact with it. Detailed qualitative analysis determined that significant disturbances were most prominent in components of skilled reaching that involved fine manipulation of the distal muscles, especially the wrist and digits. While some components of the reaching impairment were found to partially recover at 4 weeks post-surgery, the impairments in these distal motor movements persisted and there was no significant improvement in overall success. These results suggest that the collagenase model of intracerebral hemorrhage produces a functional impairment that most severely affects fine control of the distal forelimb and paw. PMID- 17346687 TI - 1H and 51V NMR investigations of the molecular nature of implant-derived vanadium ions in osteoarthritic knee-joint synovial fluid. AB - BACKGROUND: High field (1)H and (51)V NMR spectroscopies were employed to determine the oxidation state and complexation status of vanadium ions in intact osteoarthritic knee-joint synovial fluid (OA SF) when pre-added as V(III)((aq.)), V(IV)((aq.)) and V(V)((aq.)). METHODS: Aliquots of each vanadium solution were added to the SF samples and their (1)H NMR spectra recorded. (51)V NMR spectra were also recorded for the samples to which V(III)((aq.)) had been added. Theoretical computer simulations of the competitive complexation of vanadium ions by a range of low-molecular-mass biomolecules were also performed. RESULTS: The spectroscopic results demonstrated that addition of vanadium ions to intact OA SF gave rise to their complexation by a range of low-molecular-mass biomolecules. The results indicated the physiologically-significant complexing abilities of histidine, threonine, glycine, tyrosine and citrate for each of the added metal ions. The computer simulations revealed that the relative capacity of OA SF complexants to compete for available V(III), V(IV) and V(V) ions reflected the thermodynamic stability constants for such complexes and their available concentrations in this biofluid. CONCLUSIONS: Since comparatively low concentrations of added metal ion are required to selectively influence spectral properties, the "speciation" of prostheses-derived metal ions in biofluids and tissues can be ascertained through the facile employment of high resolution NMR spectroscopy. PMID- 17346686 TI - Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension. AB - OBJECTIVE: It has been reported that dehydroepiandrosterone is a pulmonary vasodilator and inhibits chronic hypoxia-induced pulmonary hypertension. Additionally, dehydroepiandrosterone has been shown to improve systemic vascular endothelial function. Thus, we hypothesized that chronic treatment with dehydroepiandrosterone would attenuate hypoxic pulmonary hypertension by enhancing pulmonary artery endothelial function. METHODS AND RESULTS: Rats were randomly assigned to five groups. Three groups received food containing 0, 0.3, or 1% dehydroepiandrosterone during a 3-wk-exposure to simulated high altitude (HA). The other 2 groups were kept at Denver's low altitude (LA) and received food containing 0 or 1% dehydroepiandrosterone. Dehydroepiandrosterone dose dependently inhibited hypoxic pulmonary hypertension (mean pulmonary artery pressures after treatment with 0, 0.3, and 1% dehydroepiandrosterone=45+/-5, 33+/ 2*, and 25+/-1*# mmHg, respectively. *P<0.05 vs. 0% and # vs. 0.3%). Dehydroepiandrosterone (1%, 3 wks) treatment started after rats had been exposed to 3-wk hypoxia also effectively reversed established hypoxic pulmonary hypertension. Pulmonary artery rings isolated from both LA and HA rats treated with 1% dehydroepiandrosterone showed enhanced relaxations to acetylcholine and sodium nitroprusside, but not to 8-bromo-cGMP. In the pulmonary artery tissue from dehydroepiandrosterone-treated LA and HA rats, soluble guanylate cyclase, but not endothelial nitric oxide synthase, protein levels were increased. CONCLUSION: These results indicate that the protective effect of dehydroepiandrosterone against hypoxic pulmonary hypertension may involve upregulation of pulmonary artery soluble guanylate cyclase protein expression and augmented pulmonary artery vasodilator responsiveness to nitric oxide. PMID- 17346688 TI - Sodium selenite inhibits interleukin-6-mediated androgen receptor activation in prostate cancer cells via upregulation of c-Jun. AB - BACKGROUND: It has been suggested that interleukin-6 (IL-6) may modulate androgen receptor (AR) action to accelerate prostate cancer (PCa) progression. Selenium compounds are highly recommended as a promising chemopreventive agent for PCa. This study was to determine if selenium can repress IL-6 mediated AR action in PCa progression. METHODS: Cell proliferation, prostate-specific antigen, gene transfer, and Western blot assays were used to study the effects of sodium selenite and methylseleninic acid on IL-6 mediated AR action on an AR expressing human prostate cancer cell line, LNCaP. RESULTS: We found that sodium selenite, but not methylseleninic acid, significantly (p<0.05) inhibited IL-6-induced trans activating activity of AR and cell proliferation in LNCaP cells. Interestingly, although sodium selenite did not show effect on activation of both STAT3 and ERK1/2 in the presence of IL-6, an increased expression of c-Jun was detected in cells after treatment with sodium selenite. Indeed, we showed overexpression of c Jun blocked IL-6-induced AR activation. CONCLUSIONS: Taken together, our results suggest that sodium selenite not methylseleninic acid can inhibit IL-6-mediated AR activation by increased c-Jun in LNCaP cells. Sodium selenite may be a proper selenium form for further testing its potency on intervening IL-6-mediated PCa progression. PMID- 17346689 TI - Biological variation of Cartilage Oligomeric Matrix Protein (COMP): a proposal to interpret laboratory serial testing. PMID- 17346690 TI - Possibilistic approach for biclustering microarray data. AB - Biclustering has emerged as an important method for analyzing gene expression data from microarray technology. It allows to identify groups of genes which behave similarly under a subset of conditions. As a gene may play more than one biological role in conjunction with distinct groups of genes, non-exclusive biclustering algorithms are required. In this paper we propose a new method to obtain potentially-overlapping biclusters, the Possibilistic Spectral Biclustering algorithm (PSB), based on Fuzzy Technology and Spectral Clustering. We tested our method on S. cerevisiae cell cycle expression data and on a human cancer dataset, validating the obtained biclusters using known classifications of conditions and GO Term Finder for functional annotations of genes. Results are available at http://decsai.ugr.es/ approximately ccano/psb. PMID- 17346691 TI - Source localization of focal ventricular arrhythmias using linear estimation, correlation, and back propagation networks. AB - Catheter-based approaches used in the localization and treatment of the source of heart rhythm disturbances (arrhythmias) have become popular, because they do not require highly invasive and risky open-chest operations. In most of the existing approaches, mapping of the outer surface (epicardium) is not possible even though arrhythmic substrates involving epicardial and subepicardial layers account for about 15% of the ventricular tachycardias. In this study, we report a feasibility study of a novel mapping approach targeting the epicardium which is based on the measurements of multielectrode catheters placed in the coronary veins. We investigated three methods in determining the most probable region of early activation, i.e., the region that contains the source of the abnormal activation on the heart, using only a set of sparse venous catheter recordings. The methods we proposed here were the linear estimation, correlation, and the back propagation networks. The linear estimation technique hypothesized the relationship between venous catheter measurements and unmeasured epicardial sites based on a previously recorded training data set. The correlation method included a comparative analysis between test and training epicardial activation time maps based on the measured values from the venous sites. In the back propagation method, the input layer consisted of the source data in the form of 42 nodes which were the activation time values from the intravenous catheter leads. We used two hidden layers with 600 and 500 nodes, respectively. The output layer consisted of 28 nodes in the output layer that corresponded to the manually selected early activation regions on the epicardium. The results of the linear estimation and the correlation methods showed that they could be used as a good predictor for the region of early activation, and thus, these approaches may be employed to direct a subsequent more focused electrophysiological study and curative radiofrequency (RF) ablation. The back propagation network approach performed relatively well for the right ventricularly paced beats and the results demonstrated its potential as a supporting technique to the estimation and correlation methods. The results of this study encourage further investigation and provides evidence that an epicardial mapping approach based on the venous catheter recordings is feasible and can provide adequate accuracy for clinical applications. PMID- 17346692 TI - An integrated approach to breast diseases and breast cancer registry and research: BDRS as a web-based multi-institutional model. AB - Accurate, complete, and timely health data sources are essential for progress in health care. Registry and research systems are foundations for conducting clinical and epidemiological research. Developing countries lack these systems due to the scarcity of the resources allocated for health information systems. In this study, we provide an integrated model for Turkey in order to optimize the utilization of resources. The Breast Diseases Registry system (BDRS) is implemented as an integrated disease-specific system for breast diseases in order to obtain a comprehensive use of patient health data for research and Breast Cancer Registry as well as an ancillary clinical tool. PMID- 17346693 TI - High-resolution fate map of the snail Crepidula fornicata: the origins of ciliary bands, nervous system, and muscular elements. AB - The littorinimorph gastropod Crepidula fornicata shows a spiralian cleavage pattern and has been the subject of studies in experimental embryology, cell lineage, and the organization of the larval nervous system. To investigate the contribution of early blastomeres to the veliger larva, we used intracellular cell lineage tracers in combination with high-resolution confocal imaging. This study corroborates many features derived from other spiralian fate maps (such as the origins of the hindgut and mesoderm from the 4d mesentoblast), but also yields new findings, particularly with respect to the origins of internal structures, such as the nervous system and musculature that have never been described in detail. The ectomesoderm in C. fornicata is mainly formed by micromeres of the 3rd quartet (principally 3a and 3b), which presumably represents a plesiomorphic condition for molluscs. The larval central nervous system is mainly formed by the micromeres of the 1st and 2nd quartet, of which 1a, 1c, and 1d form the anterior apical ganglion and nerve tracks to the foot and velum, and 2b and 2d form the visceral loop and the mantle cell. Our study shows that both first and second velar ciliary bands are generated by the same cells that form the prototroch in other spiralians and apparently bear no homology to the metatroch found in annelids. PMID- 17346694 TI - Effects of chromium on photosynthetic and photoreceptive apparatus of the alga Chlamydomonas reinhardtii. AB - Chromium is a highly toxic non-essential metal for microorganisms and plants. Due to its widespread industrial use, chromium (Cr) has become a serious pollutant in diverse environmental settings. The presence of Cr leads to the selection of algal populations able to tolerate high levels of Cr compounds. The diverse Cr resistance mechanisms displayed by microorganisms include biosorption, diminished accumulation, precipitation, reduction of Cr(6+) to Cr(3+), and chromate efflux. In this paper we describe the effects of Cr(6+) (the more toxic species) on the photosynthetic and photoreceptive apparatus of the fresh water unicellular alga Chlamydomonas reinhardtii. We measured the effect of the heavy metal by means of in vivo absorption microspectroscopy of both the thylakoid compartments and the eyespot. The decomposition of the overall absorption spectra in pigment constituents indicates that Cr(6+) induced a complete pheophinitization of the chrorophylls and a modification of the carotenoids present in the eyespot only when its concentration is equal or greater than 10 microM. Due to this low tolerance level, C. reinhardtii could be used as indicator of Cr pollution, but it is not feasible for bioremediation purposes. PMID- 17346695 TI - Effects of allyl isothiocyanate from horseradish on several experimental gastric lesions in rats. AB - Allyl isothiocyanate is well known to be a principal pungent constituent of horseradish and an agonist for transient receptor potential (TRP) A1. Ally isothiocyanate markedly inhibited the formation of gastric lesions induced by ethanol (1.5 ml/rat, p.o.), 0.6 M HCl (1.5 ml/rat, p.o.), 1% ammonia (1.5 ml/rat, p.o.), and aspirin (150 mg/kg, p.o.) (ED(50)=1.6, 2.2, 1.7, ca. 6.5 mg/kg, p.o.). It also significantly inhibited the formation of gastric lesions induced by indomethacin (20 mg/kg, p.o.), though the inhibition was ca. 60% at a high dose (40 mg/kg, p.o.). Furthermore, several synthetic isothiocyanate compounds also significantly inhibited ethanol and indomethacin-induced gastric lesions. Whereas, TRPV1 agonists, capsaicin and piperine, inhibited gastric lesions induced by ethanol, 1% ammonia, and aspirin, but had less of an effect on 0.6 M HCl-induced gastric lesions. With regard to mode of action, the protective effects of ally isothiocyanate on ethanol-induced gastric lesions were attenuated by pretreatment with indomethacin, but not with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME), or ruthenium red. Pretreatment with indomethacin reduced the protective effects of piperine, and L-NAME reduced the effects of capsaicin and omeprazole. Furthermore, ruthenium red reduced the effects of capsaicin, piperine, and omeprazole. These findings suggest that endogenous prostaglandins play an important role in the protective effect of allyl isothiocyanate in ethanol-induced gastric lesions different from capsaicin, piperine, and omeprazole. PMID- 17346696 TI - Magnolia ovovata extract and its active component magnolol prevent skin photoaging via inhibition of nuclear factor kappaB. AB - Transcriptional activity of nuclear factor kappaB (NF-kappaB) is induced by environmental signals including inflammation, UV irradiation and oxidative stress. It was shown that the NF-kappaB activity greatly contributes to the skin photoaging process. Thus, it is plausible that NF-kappaB inhibitors could directly prevent skin photoaging. In this study, we found that Magnolia ovovata extract inhibited NF-kappaB-mediated gene expression and demonstrated that external swabbing with Magnolia extract preventing skin photoaging processes through keratinocyte hyperproliferation and degradation of collagen fibers in mice skin. We have identified magnolol as the solely responsible active compound in Magnolia extract. Magnolol effectively inhibited the NF-kappaB-dependent transcription, but no effect was observed with other inducible transcription factors such as activator protein-1 (AP-1) and cyclic-AMP responsive element binding protein (CREB). In addition, magnolol was effective in inhibiting the production of basic fibroblast growth factor (bFGF) and matrix metalloprotease-1 (MMP-1) from the cells overexpressing p65, a major subunit of NF-kappaB. Although magnolol did not affect the phosphorylation and degradation of IkappaBalpha, it inhibited the nuclear translocation of the activated NF-kappaB. These findings suggest that Magnolia extract and its active component magnolol can be used to prevent the skin photoaging via inhibiting NF-kappaB by external topical application. PMID- 17346697 TI - A quantitative method for measuring the antitumor potency of recombinant human endostatin in vivo. AB - Recombinant human endostatin (rhEndostatin) has been shown to inhibit tumor growth, but the variable antitumor activity of different rhEndostatin preparations has necessitated the development of an accurate, reproducible in vivo bioassay for evaluating the rhEndostatin activity. To assess the in vivo antitumor efficacy of rhEndostatin, H22 tumor-bearing mice received three doses of rhEndostatin and the potency of rhEndostatin preparations in inhibiting tumor growth was determined by ED(50)-potency assay and validated by dose-response parallel-line assay. There was a consistent and highly reproducible linear regression relationship between rhEndostatin dosage and tumor growth inhibition rate. The ED(50) values were determined from dose-response regression lines for seven rhEndostatin preparations with high reproducibility. On the basis of the current study, the potency of rhEndostatin preparations was assigned a value of 6.09 x 10(5) U/ampoule and a 95% confidence limit of 5.96 x 10(5)-6.22 x 10(5). We consider that this procedure can be served as a potential candidate pharmacopoeial method for potency measurement of different rhEndostatin preparations. PMID- 17346698 TI - Effects of dextrorotatory morphinans on brain Na+ channels expressed in Xenopus oocytes. AB - We previously demonstrated that dextromethorphan (DM; 3-methoxy-17 methylmorphinan) analogs have neuroprotective effects. Here, we investigated the effects of DM, three of its analogs (DF, 3-methyl-17-methylmorphinan; AM, 3 allyloxy-17-methoxymorphian; and CM, 3-cyclopropyl-17-methoxymorphinan) and one of its metabolites (HM; 3-methoxymorphinan), on Na(+) channel activity. We used the two-microelectrode voltage-clamp technique to test the effects of DM, DF, AM, CM and HM on Na(+) currents (I(Na)) in Xenopus oocytes expressing cRNAs encoding rat brain Nav1.2 alpha and beta1 or beta2 subunits. In oocytes expressing Na(+) channels, DM, DF, AM and CM, but not HM, induced tonic and use-dependent inhibitions of peak I(Na) following low- and high-frequency stimulations. The order of potency for the inhibition of peak I(Na) was AM-CM > DM=DF. The DM, DF, AM and CM-induced tonic inhibitions of peak I(Na) were voltage-dependent, dose dependent and reversible. The IC(50) values for DM, DF, AM and CM were 116.7+/ 14.9, 175.8+/-16.9, 38.6+/-15.5, and 42.5+/-8.5 microM, respectively. DM and its analogs did not affect the steady-state activation and inactivation voltages. AM and CM, but not DM and DF, inhibited the plateau I(Na) more effectively than the peak I(Na) in oocytes expressing inactivation-deficient I1485Q-F1486Q-M1487Q (IFMQ3) mutant channels; the IC(50) values for AM and CM in this system were 8.4+/-1.3 and 8.7+/-1.3 microM, respectively, for the plateau I(Na) and 43.7+/ 5.9 and 32.6+/-7.8 microM, respectively, for the peak I(Na). These results collectively indicate that DM and its analogs could be novel Na(+) channel blockers acting on the resting and open states of brain Na(+) channels. PMID- 17346700 TI - Phosphorescence decay time measurements using intensity correlation spectroscopy. AB - In this paper, we report on phosphorescence measurements for oxygen dynamics in cells by means of a correlation method, which is an expansion of the fluorescence correlation spectroscopy. The intensity correlation function of the emission excited by a pulsed light source was measured. With changing the pulse timing, both the fluorescence correlation function and the decay time of phosphorescence could be analyzed. This method was applied for the analysis of the oxygen dynamics in HeLa cells stained by Pd(II)-porphine. The decay function consisted of two exponential components, which might be attributed to free and protein bound forms of Pd(II)-porphine in the cell, respectively. The relative change of the oxygen concentration under normal and uncoupled respiration conditions was also measured. The simplicity of this method is a great advantage in the biological applications. Although the current system we used was limited in the temporal resolution, the method is in principle applicable to faster decay time measurements down to the nano-second range of the fluorescence decay times. PMID- 17346699 TI - Effect of experimental hypercholesterolaemia on K+ channel alpha-subunit mRNA levels in rabbit hearts. AB - We investigated the effect of dietary cholesterol on gene transcription of delayed rectifier (I(Kr) - ERG1 and I(Ks) - KvLQT1) and transient outward (I(to,fast) - Kv4.2 and Kv4.3) potassium channel subunits in rabbit hearts using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). While the level of Kv4.3 mRNA did not change, both Kv4.2 and ERG1 mRNAs were downregulated, whereas the level of KvLQT1 was increased in hypercholesterolaemic rabbits, indicating that hypercholesterolaemia altered ventricular K(+) channel alpha-subunit gene transcription. PMID- 17346701 TI - Filopodia are induced by aquaporin-9 expression. AB - Understanding filopodial formation in motile cells is a pertinent task in cell biology. In the present study we show that expression of the human water channel aquaporin-9 (AQP9) in different cell lines induces the formation of numerous filopodial extensions. Several lines of evidence support the role of aquaporins functioning both as a water channel and signaling participant. The number of filopodia is decreased by site-directed serine substitutions in putative PKC binding or -phosphorylation sites at amino acid position 11 and 222 in AQP9. The filopodial phenotype obtained with wild-type AQP9 is associated with elevated levels of active Cdc42, while serine-deleted mutants have reduced levels of GTP Cdc42. Co-transfection with inhibitory N-WASP CRIB completely abolishes wild-type AQP9-induced filopodia formation. Active PKC(zeta) phosphorylates wild-type AQP9 and myristoylated PKC(zeta) pseudosubstrate inhibits the formation of filopodia in AQP9-expressing cells. Expression of wild-type AQP9, but not mock or serine substituted mutants, increases sensitivity to hypo-osmolaric conditions, yielding a rapid morphological rounding of cells and cell death starting as early as 24 h post-transfection. We propose that increased water influx through AQP9 is critically involved in the formation of membrane protrusions, and that AQP9 induced actin polymerization is augmented by activation of Cdc42 and PKC(zeta). PMID- 17346702 TI - The impact of glia-derived extracellular matrices on the barrier function of cerebral endothelial cells: an in vitro study. AB - The blood-brain barrier (BBB) is composed of the cerebral microvascular endothelium, which, together with astrocytes, pericytes, and the extracellular matrix (ECM), contributes to a "neurovascular unit". It was our objective to clarify the impact of endogenous extracellular matrices on the barrier function of BBB microvascular endothelial cells cultured in vitro. The study was performed in two consecutive steps: (i) The ECM-donating cells (astrocytes, pericytes, endothelial cells) were grown to confluence and then removed from the growth substrate by a protocol that leaves the ECM behind. (ii) Suspensions of cerebral endothelial cells were seeded on the endogenous matrices and barrier formation was followed with time. In order to quantify the tightness of the cell junctions, all experiments were performed on planar gold-film electrodes that can be used to read the electrical resistance of the cell layers as a direct measure for endothelial barrier function (electric cell-substrate impedance sensing, ECIS). We observed that endogenously isolated ECM from both, astrocytes and pericytes, improved the tightness of cerebral endothelial cells significantly compared to ECM that was derived from the endothelial cells themselves as a control. Moreover, when cerebral endothelial cells were grown on extracellular matrices produced by non-brain endothelial cells (aorta), the electrical resistances were markedly reduced. Our observations indicate that glia-derived ECM - as an essential part of the BBB - is required to ensure proper barrier formation of cerebral endothelial cells. PMID- 17346703 TI - Positioning of the mouse Hox gene clusters in the nuclei of developing embryos and differentiating embryoid bodies. AB - Expression of Hox genes located on different chromosomes is precisely regulated and synchronized during development. In order to test the hypothesis that the Hox loci might cluster in nuclear space in order to share regulatory components, we performed 3D FISH on cryosections of developing mouse embryos and differentiating embryoid bodies. We did not observe any instances of co-localization of 4 different Hox alleles. Instances of 2 different alleles touching each other were found in 20-47% of nuclei depending on the tissue. The frequency of such "kissing" events was not significantly different in cells expressing a high proportion of the Hox clusters when compared to cells expressing none or only a few Hox genes. We found that the HoxB and HoxC clusters, which are located in gene-rich regions, were involved more frequently in gene kissing in embryonic nuclei. In the case of HoxB, this observation correlated with the positioning of the corresponding chromosome towards the interior of the nucleus. Our results indicate that co-regulation of the different Hox clusters is not associated with co-localization of the loci at a single regulatory compartment and that the chromosomal context may influence the extent to which they contact each other in the nucleus. PMID- 17346704 TI - 5-HT4 receptor and Alzheimer's disease: the amyloid connection. PMID- 17346705 TI - Reaction to topical capsaicin in spinal cord injury patients with and without central pain. AB - Central neuropathic pain is a debilitating and frequent complication to spinal cord injury (SCI). Excitatory input from hyperexcitable cells around the injured grey matter zone is suggested to play a role for central neuropathic pain felt below the level of a spinal cord injury. Direct evidence for this hypothesis is difficult to obtain. Capsaicin, activating TRPV1 receptors on small sensory afferents, induces enhanced cellular activity in dorsal horn neurons and produces a central mediated area of secondary hyperalgesia. We hypothesized that sensory stimuli and capsaicin applied at and just above the level of a spinal cord injury which already is hyperexcitable, would cause enhanced responses in patients with central pain at the level of injury compared to patients without neuropathic pain and healthy controls. Touch, punctuate stimuli, cold stimuli and topical capsaicin was applied above, at, and below injury level in 10 SCI patients with central pain below a thoracic injury, in 10 SCI patients with a thoracic injury but without neuropathic pain, and in corresponding areas in 10 healthy control subjects. The study found increased responses to touch at injury level compared to controls (p=0.033) and repetitive punctuate stimuli above and at injury level compared to controls and pain-free SCI patients (p<0.04) but not an increased response to capsaicin in patients with central pain. These results suggest that SCI patients with below-level pain have increased responses to some but not all sensory input at the level of injury. PMID- 17346706 TI - Preliminary analysis of cold stress responsive proteins in Mesocestoides corti larvae. AB - Many parasites undergo sudden changes in environmental conditions at some stage during their life cycle. The molecular response to this variation is characterised by a rapid transcriptional activation of a specific set of genes coding for proteins generically known as stress proteins. They appear to be also involved in various biological processes including cell proliferation and differentiation. The platyhelminth parasite, Mesocestoides corti (Cestoda) presents important properties as a model organism. Under stress conditions, key molecules involved in metabolic pathways as well as in the growth and differentiation of the parasite can be identified. 2D protein expression profile of tetrathyridia of M. corti, submitted to nutritional starvation and cold stress is described, as well as the recovery pattern. A set of specifically expressed proteins was observed in each experimental condition. Quantitative and qualitative differences and stress recovery pattern are also reported. This work makes evident the high plasticity and resistance to extreme environmental conditions of these parasites at the molecular level. PMID- 17346707 TI - Taenia crassiceps organic acids detected in cysticerci. AB - Taenia crassiceps cysticerci is used as an experimental model to cysticercosis studies; however there are subcutaneous cases of cysticercosis caused by these cysticerci. It remains unclear in the literature the energetic and fatty acid metabolism in cestodes. Its metabolic study may provide knowledge of pathways that may serve as potential anti-helminthic drugs sites of action. In this work we studied the citric acid cycle organic acids and the fatty acid oxidation in cysticerci removed from mice with 21 and 42 days of infection in two different evolutive stages: growing and final. The organic acids were extracted using perchloric acid and analyzed by HPLC methodology. We found significant statistically differences in oxalate, malate, lactate, and beta-hydroxybutirate concentrations between cysticerci. These results indicate the aerobic metabolism in vivo in spite of the low oxygen concentration of its habitat, and also indicate the presence of fatty acid oxidation as an alternative energetic source. PMID- 17346708 TI - GTF2IRD1 regulates transcription by binding an evolutionarily conserved DNA motif 'GUCE'. AB - GTF2IRD1 is a member of a family of transcription factors whose defining characteristic is varying numbers of a helix-loop-helix like motif, the I-repeat. Here, we present functional analysis of human GTF2IRD1 in regulation of three genes (HOXC8, GOOSECOID and TROPONIN I(SLOW)). We define a regulatory motif (GUCE GTF2IRD1 Upstream Control Element) common to all three genes. GUCE is bound in vitro by domain I-4 of GTF2IRD1 and mediates transcriptional regulation by GTF2IRD1 in vivo. Definition of this site will assist in identification of other downstream targets of GTF2IRD1 and elucidation of its role in the human developmental disorder Williams-Beuren syndrome. PMID- 17346709 TI - CD36 is a receptor for oxidized high density lipoprotein: implications for the development of atherosclerosis. AB - Atherosclerotic plaques result from the excessive deposition of cholesterol esters derived from lipoproteins and lipoprotein fragments. Tissue macrophage within the intimal space of major arterial vessels have been shown to play an important role in this process. We demonstrate in a transfection system using two human cell lines that the macrophage scavenger receptor CD36 selectively elicited lipid uptake from Cu(2+)-oxidized high density lipoprotein (HDL) but not from native HDL or low density lipoprotein (LDL). The uptake of oxHDL displayed morphological and biochemical similarities with the CD36-dependent uptake of oxidized LDL. CD36-mediated uptake of oxidized HDL by macrophage may therefore contribute to atheroma formation. PMID- 17346710 TI - STAT1 regulates p73-mediated Bax gene expression. AB - Although signal transducer and activator of transcription 1 (STAT1) mediated regulation of p53 transcription and apoptosis has been previously reported, modulation of other members of the p53 family of transcription factors remains poorly understood. In this study, we found that STAT1 and TA-p73 can interact directly and that p73-mediated Bax promoter activity was observed to be reduced by STAT1 expression in a p53-independent manner for which STAT1 Tyrosine-701 and Serine-727 are key residues. This study presents the first report physically linking STAT1 and TA-p73 signalling and highlights the modulation of the Bax promoter in the context of IFN-gamma stimulation. PMID- 17346711 TI - Dissecting yeast Hog1 MAP kinase pathway using a chemical genetic approach. AB - Using a chemical genetic approach, we identified four novel physiological substrates of Hog1 kinase (Krs1, Tdh3, Hsp26, and Shm2). These substrates suggest plausible mechanisms for actin reorganization, cell cycle arrest and regulation of protein synthesis observed upon osmotic stress. We further show that the human homolog of Shm2 (SHMT1) is a novel physiological substrate of p38 MAP kinase in vitro and in vivo. Down-regulation of its enzymatic activity was observed following p38-mediated phosphorylation revealing a potential cancer-modulating property of p38 MAP kinase. This screen has uncovered several novel Hog1 substrates that provide new avenues for investigation into the mechanism of osmoadaptation by this kinase. PMID- 17346712 TI - NADPH oxidase 5 (NOX5) interacts with and is regulated by calmodulin. AB - Superoxide generation by NADPH oxidase 5 (NOX5) is regulated by Ca(2+) through intramolecular activation of the C-terminal catalytic domain by the EF-hand containing N-terminal regulatory domain. The C terminus contains a consensus calmodulin-binding domain (CaMBD), which, however, is not the binding site of the N-terminal regulatory domain. Here we show by pull down, cross-linking, fluorimetry and by enzymatic assays, that calmodulin binds to this CaMBD in a Ca(2+)-dependent manner, changes its conformation and increases the Ca(2+) sensitivity of the N terminus-regulated enzymatic activity. This mechanism represents an additional sophistication in the regulation of superoxide production by NOX5. PMID- 17346713 TI - Mutations in p97/VCP induce unfolding activity. AB - A comparison of the protein sequences of various two-domain AAA+ ATPases revealed a striking difference in the residues lining the central pore of the D1 domain. The protein unfoldases of the bacterial Clp family and the archaeal VAT protein have at least one aromatic residue in the central D1 pore. In contrast, none of the members of the eukaryotic p97/VCP protein family has an aromatic residue in the D1 pore. The protein unfolding activity of VAT and other AAA+ ATPases is critically dependent on the presence of aromatic residues in this central pore. Unfoldase activity has not been demonstrated for the p97/VCP family in vitro. Thus, we exchanged the two aliphatic residues leucine and alanine of the D1 pore for aromatic tyrosine residues in full length p97 and in p97DeltaN, a truncated form of p97 lacking the N domain. We found that the mutant p97DeltaN variants with a single tyrosine or with two tyrosine residues in the central pore of D1 unfold the Clp family and VAT model substrate YFP-ssrA, whereas full length p97 with aromatic pore residues and wild-type p97 or p97DeltaN do not. Thus, p97 can exert unfoldase activity in vitro, provided that a single tyrosine residue is introduced into the D1 pore and that the N domain is deleted. PMID- 17346714 TI - Two HlyIIR dimers bind to a long perfect inverted repeat in the operator of the hemolysin II gene from Bacillus cereus. AB - HlyIIR is a negative transcriptional regulator of hemolysin II gene from B. cereus. It binds to a long DNA perfect inverted repeat (44bp) located upstream the hlyII gene. Here we show that HlyIIR is dimeric in solution and in bacterial cells. No protein-protein interactions between dimers and no significant modification of target DNA conformation upon complex formation were observed. Two HlyIIR dimers were found to bind to native operator independently with Kd level in the nanomolar range. The minimal HlyIIR binding site was identified as a half of the long DNA perfect inverted repeat. PMID- 17346715 TI - Effects of the pharmacologic manipulation of testosterone on cognitive functioning in women with polycystic ovary syndrome: a randomized, placebo controlled treatment study. AB - In a previous study, we found that women with polycystic ovary syndrome (PCOS), an endocrine disorder characterized by chronic hyperandrogenism, performed more poorly than healthy, matched controls on a number of neuropsychological tests, in particular tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory. This randomized, placebo-controlled trial was undertaken to investigate whether pharmacologic manipulation of free testosterone (free T) levels in women with PCOS might affect their performance on cognitive tests. Nineteen women with PCOS completed a battery of neuropsychological tests before and after 3 months of treatment with either an anti-androgen (cyproterone acetate) plus estrogen or with a placebo. Hormone treatment of women with PCOS caused a significant reduction in their free T levels but did not affect performance on tests visuospatial ability, verbal memory, manual dexterity, or perceptual speed. Women treated with hormone therapy did, however, demonstrate an improvement in their performance on a test of verbal fluency compared to their pre-treatment scores. These findings suggest that changes in free T levels do not have a significant impact on cognitive performance in women with PCOS, although reductions in free T may be beneficial for verbal fluency. PMID- 17346716 TI - An inertial and magnetic sensor based technique for joint angle measurement. AB - This paper describes the design and evaluation of a miniature kinematic sensor based three dimensional (3D) joint angle measurement technique. The technique uses a combination of rate gyroscope, accelerometer and magnetometer sensor signals. The technique enables 3D inter-segment joint angle measurement and could be of benefit in a variety of applications which require monitoring of joint angles. The technique is not dependent on a fixed reference coordinate system and thus may be suitable for use in a dynamic system such as a moving vehicle. The technique was evaluated by applying it to joint angle measurement of the ankle joint. Experimental results show that accurate measurement of ankle joint angles is achieved by the technique during a variety of lower leg exercises including walking. PMID- 17346718 TI - Rapid headspace solid-phase microextraction-gas chromatographic-time-of-flight mass spectrometric method for qualitative profiling of ice wine volatile fraction. III. Relative characterization of Canadian and Czech ice wines using self-organizing maps. AB - The determination of volatile and semi-volatile components of ice wine aroma was realized throughout the development of a rapid headspace solid-phase microextraction-gas chromatography-time-of-flight mass spectrometry (SPME-GC-TOF MS) analytical method (Part I) and its application to the analysis of 137 samples produced in Canada and Czech Republic and collected directly from the producing wineries (Part II). In this Part III study, the complex matrix resulting from the analysis of the 58 compounds selected for each sample as described in Part II, was submitted to critical interpretation by using a self-organizing map (SOM) technique. Results were commented in terms of relative characterization of samples according to their geographical origin, grape varieties, and vintage years. When clear clustering was obtained, the most determinant compounds responsible for the observed differentiations were identified and further discussed. PMID- 17346717 TI - Modulation of neonatal growth plate development by ex vivo intermittent mechanical stress. AB - Although growth plate response to mechanical stress has been increasingly studied, our understanding of mechanical modulation of neonatal growth plate is incomplete, especially concerning biochemical changes. This study was designed to explore the cellular and biochemical responses of the cranial base growth plate (CBGP) explant upon cyclic loading. The growth plate with subchondral bone was aseptically isolated from each of 24 neonatal rabbits and fixated in an organ culture system. Cyclic loading was applied to growth plate explants at 200 mN and 1 Hz for 60 min (N=12), whereas control explants were immersed in organ culture for 60 min without mechanical loading (N=12). Computerized image analysis revealed that cyclic loading induced significantly more proliferating chondrocytes than unloaded controls (p<0.001), as well as significantly higher growth plate height at 856+/-30 microm than the unloaded controls at 830+/-36 microm (p<0.05). Immunoblotting with monoclonal antibodies (mAb) disclosed that the average mAb binding area for chondroitin sulfate was significantly higher in the loaded specimens than the unloaded controls at (p<0.001). The average mAb binding area for keratan sulfate was also significantly higher in the loaded specimens than the unloaded controls (p<0.01). Biochemical analysis showed that the average total hyaluronan content of loaded specimens at 0.25+/-0.06 microg/microg DNA was significantly higher than the unloaded controls at 0.09+/ 0.05 microg/microg DNA (p<0.01). Taken together, these data suggest that brief doses of cyclic, intermittent forces activate cellular and molecular responses in the CBGP ex vivo. Whether hyaluronan-mediated pathway is involved in the biological responses of growth plate to mechanical loading warrants additional investigations. PMID- 17346719 TI - Investigation of the feasibility of TiO(2) nanotubes for the enrichment of DDT and its metabolites at trace levels in environmental water samples. AB - TiO(2) nanotubes, novel nanomaterials synthesized from hydrothermal treatment, were investigated for being used as a new solid-phase extraction adsorbent with o,p'-DDT, [1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, p,p'-DDT, [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane] and its principle metabolites p,p'-DDD, [1,1-dichloro-2,2-bis(4-chlorophenyl)ethane] and p,p'-DDE [1,1-(2,2 dichloro-ethanylidene)-bis(4-chlorobenzene)] as the target analytes. Several factors such as eluant and its volume, the sample pH, sample volume and the flow rate of samples, were optimized. The effect of humic acid, which is often present in natural water system, was also investigated. Under the optimal conditions, lower detection limits of 0.0031, 0.0037, 0.0053 and 0.0025 ng mL(-1) for p,p' DDD, p,p'-DDT, o,p'-DDT and p,p'-DDE, respectively, were obtained. The proposed method was successfully applied to the analysis of the target compounds in several environmental water samples. Good recoveries over the range of 81.2-115% were obtained. These results indicated that titanium nanotubes had enormous potential in environmental field as a novel SPE adsorbent material. PMID- 17346720 TI - Comparison of strong anion-exchangers for the purification of a PEGylated protein. AB - We have studied the effect of protein PEGylation on ion-exchange adsorption using bovine serum albumin as a model system. The free sulfhydryl group of BSA, located on cysteine 34, was PEGylated using the maleimido-PEG chemistry. Several different BSA preparations were screened for extent of reaction using a 30 kDa PEG reagent. The highest yielding BSA preparation was PEGylated using linear 12 kDa and 30 kDa PEG reagents at the 1 liter scale. The PEGylated reaction mixture was purified by anion-exchange gradient elution chromatography to remove native protein and aggregates. Purity following anion-exchange chromatography was >90% as determined by analytical size exclusion chromatography. The elution salt concentration decreased with increasing PEG chain length. Breakthrough studies on six commercially available anion-exchange stationary phases with purified PEG-BSA conjugates confirm a very large decrease in dynamic binding capacity compared to the native protein. The decrease in dynamic binding capacity is likely due to modulation of electrostatic interactions caused by the neutral PEG chain and increased mass transfer resistance associated with the large size of the molecule. Of the stationary phases evaluated, the open porous structure of the agarose based ion-exchangers resulted in the highest dynamic binding capacities for the PEG-BSA conjugates. Frontal analysis experiments demonstrate use of this technique for purification of PEGylated proteins. A stationary phase that tended to exclude the large PEG-BSA conjugate was very efficient in removing native protein from a crude reaction mixture by frontal analysis. PMID- 17346721 TI - A new poly(phthalazine ether sulfone ketone)-coated fiber for solid-phase microextraction to determine nitroaromatic explosives in aqueous samples. AB - A novel polar solid-phase microextraction (SPME) fiber coated with poly(phthalazine ether sulfone ketone) (PPESK) was prepared by immersion precipitation technique. The microstructure of the coating exhibits a sponge-like sublayer supporting a dense cracking shaped top layer (about 1 microm in thickness). This coating shows long lifetime (up to 100 times) and is stable at desorption temperature up to 290 degrees C due to the rigid aromatic rings in chemical structure. We evaluated the extraction-desorption properties of the PPESK fiber for nitroaromatic explosives in aqueous samples. The parameters affecting the extraction were optimized, including extraction temperature and time, salt addition, desorption temperature and time. Limits of detection (LOD), precisions and linear dynamic range for the analysis of explosives by SPME-GC/TSD or ECD were evaluated. Limits of detection of the new fiber was three orders of magnitude lower than those with carbowax/divinylbenzene (CW/DVB), and the relative standard deviation (RSD) of single fiber and fiber-to-fiber were less than 9.3 and 10.4%, respectively. The results demonstrated that the PPESK coating exhibited high extraction efficiency for nitroaromatic compounds due to the pi-pi interaction, dipole-dipole interactions and interactions by polar functional groups. The method was applied to the analysis of nitroaromatic explosives in real aqueous samples including seawater and groundwater samples, with relative recoveries better than 90.7%. PMID- 17346722 TI - Effect of disperse dye structure on dye sorption onto PLA fiber. AB - The effect of the structure of various disperse dyes on their percentage sorption onto polylactide (PLA) is explained using molecular modeling. The interaction energies between the dyes and PLA have been calculated, and a linear equation has been developed to predict the percentage sorption on PLA based on the dye-PLA interaction energy. The predicted percentage sorption for a dye is shown to agree with its experimentally obtained percentage sorption on commercial PLA fabric and on PLA fiber extruded in our laboratory. Within the dyes, the functional groups that form the strongest interactions with PLA are -N(C(2)H(4)OCOCH(3))(2), (CO)(2)NC(3)H(6)OCH(3), -SO(2)NHC(6)H(5), -NO(2), -CN(NH)C(6)H(4), and CH(CO)(2)C(6)H(4), and the groups that form the weakest interactions with PLA are -Br and -Cl. PMID- 17346723 TI - Corrosion of copper in aerated synthetic sea water solutions and its inhibition by 3-amino-1,2,4-triazole. AB - Corrosion of copper in aerated synthetic sea water (3.5% NaCl) solutions and its inhibition by 3-amino-1,2,4-triazole (ATA) have been studied using electrochemical, gravimetric, and pH measurements, along with Raman spectroscopy. Electrochemical measurements indicated that the presence of ATA and the increase of its concentration suppress the corrosion process on the copper surface. This effect decreases cathodic, anodic, and corrosion (jcorr) currents and corrosion rates (Kcorr), while increasing polarization resistance (Rp), surface coverage (theta), and inhibition efficiency (IE%). Weight loss measurements indicated that the dissolution of copper and the accompanying change of pH decreased to a minimum even after 24 days immersion due to the presence of ATA and the increase of its concentration. Raman investigations revealed that the inhibition of copper corrosion is achieved by strong adsorption of ATA molecules onto the copper surface, preventing it from being corroded easily. PMID- 17346724 TI - Influence of the electrical interface properties on the rheological behavior of sonicated soy lecithin dispersions. AB - A significant effect, on the rheological behavior, due to the electrical properties of vesicles formed from concentrated soy lecithin dispersions have been studied in this work. The rheopectic behavior of concentrated soy lecithin dispersions (120, 150, 180, 210 and 240 g L-1) prepared by swelling-light sonication-freezing-unfreezing procedure is studied and it is specially emphasized on the transition under steady shear from lamellar phase of planar sheets to closed structures as multilamellar vesicles. Samples have been exposed to a different number of sonication cycles (from 0 to 100) and the changes in the hysteresis loop area, the apparent viscosity and the electrophoretic mobility have been studied. When the number of sonication cycles increases, the size and number of bilayers of these multilamellar vesicles decrease and therefore the total number of the vesicles and the volume fraction occupied by them show an increase. PMID- 17346725 TI - A linear analysis of the effect of Faradaic currents on traveling-wave electroosmosis. AB - Net fluid flow of electrolytic solutions induced by a traveling-wave potential applied to an array of co-planar interdigitated microelectrodes has been reported. At low applied voltages the flow is driven in the direction of the traveling-wave potential, as expected by linear and weakly nonlinear theoretical studies. The flow is driven at the surfaces of the electrodes by electrical forces acting in the diffuse electrical double layer. The pumping mechanism has been analyzed theoretically under the assumption of perfectly polarizable electrodes. Here we extend these studies to include the effect of Faradaic currents on the electroosmotic slip velocity generated at the electrode/electrolyte interface. We integrate the electrokinetic equations under the thin-double-layer and low-potential approximations. Finally, we analyze the pumping of electrolyte induced by a traveling-wave signal applied to a microelectrode array using this linear model. PMID- 17346726 TI - The salivary mucin MUC5B and lactoperoxidase can be used for layer-by-layer film formation. AB - In situ ellipsometry was used to study layer-by-layer film formation on hydrophilic and hydrophobized silica surfaces by alternating sequential adsorption of human mucin MUC5B and cationic proteins lysozyme, lactoferrin, lactoperoxidase or histatin 5, respectively. The stability of the multilayers was investigated by addition of sodium dodecyl sulfate solution (SDS). Atomic force microscopy was employed to investigate morphological structures on the surfaces during the layer-by-layer film build-up. It was clearly shown that, on both hydrophilic and hydrophobized silica, only MUC5B and lactoperoxidase showed the ability for multilayer formation, resulting in an approximately linear increase in adsorbed amount and film thickness with each deposition cycle. The net increase in amounts per cycle was larger on the hydrophilic silica. Further, MUC5B needs to be adsorbed first on the hydrophilic substrates to obtain this fast build-up behavior. Generally, addition of SDS solution showed that a large fraction of the adsorbed film could be desorbed. However, films on the hydrophobized silica were more resistant to surfactant elution. In conclusion, MUC5B-cationic protein multilayers can be formed on hydrophilic and hydrophobized silica, depending on the choice of the cationic protein as well as in which order the build-up is started on hydrophilic silica. Additionally, SDS disrupts the layer-by-layer film formed by MUC5B and lactoperoxidase. PMID- 17346727 TI - Experimental and theoretical evidence of overcharging of calcium silicate hydrate. AB - Electrokinetic measurements such as electrophoresis may show an inversion of the effective surface charge of colloidal particle called overcharging. This phenomenon has been studied by various theoretical approaches but up to now very few attempts of confrontation between theory and experiment have been conducted. In this work we report electrophoretic measurements as well as Monte Carlo simulations of the electrokinetic potential for the surface of calcium silicate hydrate (CSH), which is the major constituent of hydrated cement. In the simulations, the surface charge of CSH nanoparticles in equilibrium with the ionic solution is determined by a single site characteristic and electrostatic interactions between all explicit charges at the surface and in the electric double layer. We will show that ordinary electrostatic interactions are enough to describe all experimental observations. Actually, an excellent agreement is found between experimental and simulated results without any fitting parameter, both with respect to surface titration and electrokinetic behaviour. The agreement extends over a wide range of electrostatic coupling, from a weakly charged surface with mainly monovalent counter-ions to a highly charged one with divalent counter-ions. PMID- 17346728 TI - Adsorption of carbon dioxide of 1-site and 3-site models in pillared clays: a Gibbs ensemble Monte Carlo simulation. AB - Adsorption behavior of carbon dioxide confined in pillared clays is analyzed by using constant pressure Gibbs ensemble Monte Carlo (GEMC) method. In our simulation, 1-site and 3-site models are used to represent carbon dioxide. At the 1-site model, carbon dioxide is described as a Lennard-Jones (LJ) sphere, while at the 3-site model, carbon dioxide is modeled as a three-sites linear chain represented by EPM2 potential considering the quadrapolar effect. The potential model from Yi et al. for pillared clays is used to emphasize its quasi two dimensional structure. Comparing the calculated results from the 1-site and the 3 site models at T=228.15 and 258.15 K, we observe that the adsorption amount from the two models is the same basically. However, the local density presents a significant difference, because the shoulder in the main peak near the wall from 3-site model can reflect the orientation of carbon dioxide. Accordingly, in the systematical investigation to explore the effect of porosity and pore width on the adsorption of carbon dioxide in pillared clays, the 3-site model was only used. We observe that for a narrow pore of H=1.02 nm, each isotherm shape displays type I curve, suggesting that it is not inflected by the porosity. However, for the larger pores of H=1.70 and H=2.38 nm, the increase of the porosity alters the shape of adsorption isotherms from a simple linear relation to the first order jump, indicating that the porosity is of very important factor to affect adsorption and phase behavior of fluids confined in pillared clays. The excess adsorptions of carbon dioxide at supercritical temperatures of T=323.15 and 348.15 K are also investigated. We find that the maximum exists for each excess isotherm, and the optimal pressure corresponding to the maximum increases with the pore width. However, the porosity has no significant effect on the optimal pressure. PMID- 17346729 TI - Phase behavior of the mixtures of poly(oxyethylene) (10) stearyl ether (Brij-76), 1-butanol, isooctane, and mixed polar solvents II. Water and ethylene glycol (EG) or tetraethylene glycol (TEG). AB - The phase diagrams of the pseudo-quaternary systems poly(oxyethylene) (10) stearyl ether (Brij-76)/1-butanol/isooctane/water (with equal amounts of oil and water in the presence of two nonaqueous polar solvents (NPS), ethylene glycol (EG), and tetraethylene glycol (TEG)), have been constructed at 30 degrees C. Regular fish-tail diagrams were obtained up to psi (weight fraction of EG or TEG in the mixture of polar solvents) equal to 0.5, confirming the establishment of hydrophile-lipophile balance (HLB) of the systems. The maximum solubilization capacity passed through a minimum at psi=0.2. No HLB was obtained at higher psi. The usual fish-tail diagrams were also obtained in temperature-induced phase mapping at fixed W(1) (weight fraction of 1-butanol in total amphiphile). Solubilization capacity and HLB temperature (T(HLB)) decreased with increasing psi at a fixed W(1), the effect being more pronounced for TEG than EG. A correlation between HLB temperature (T(HLB)) and HLB number (N(HLB)) of mixed amphiphiles (Brij-76+Bu) in pseudo-quaternary systems (in the presence of water and partial substitution of water with both NPS) has been established. The novelty of the work with respect to possible applications has been discussed. PMID- 17346730 TI - Study of the colloidal stability of concentrated bimodal magnetic fluids. AB - In this paper, we describe an investigation of the stability and sedimentation behavior of moderately concentrated suspensions of extremely bimodal magnetite particles, including micro- (diameter 1450 nm) and nano- (diameter 8 nm) units. An original method is used, based on the determination of the time dependence of the inductance of a coil surrounding the suspensions. The method proves to be very useful for the determination of the volume fraction of magnetic material in the sensed volume. The observed changes in the resonant frequency of a parallel LC circuit demonstrate that the addition of the magnetite nanoparticles improves the stability and slows down the settling rate of the mixed suspensions. It is proposed that the observed behavior is the result of competition between two processes. One is the formation of a cloud of nanoparticles around the large magnetite units, by virtue of which the latter are maintained at distances beyond the range of DLVO and magnetic attractive interactions. At long times, these composite units will eventually sediment when some critical size is reached, as the small particles are progressively associated with the large ones. The second mechanism is mainly predominant at short times and is related to the higher viscosity of the dispersion medium (the nanoparticles dispersed in the base fluid) for higher nanoparticle concentrations. The stability of the suspensions is discussed in terms of the competition between the two mechanisms. PMID- 17346731 TI - The electrical conductivity and surface conduction of consolidated rock cores. AB - A fully computerized high-pressure and high-temperature core holder device is simultaneously used to determine the electrical conductivity, zeta potential, and surface conductivity of consolidated rock cores in aqueous and nonaqueous systems. The total electrical conductivity of rock cores was determined by coupling streaming current and potential measurements. This shows that neglecting the surface conductivity Ksigma is crucial to converting the streaming potential into zeta potentials. It is observed that plots of the core total conductivity as a function of the electrolyte conductivity KL exhibit two behaviors. At low ionic strength, the core conductivity clearly depends on the contribution of surface conductivity behind the slip plane, whereas at higher ionic strength, the magnitude of the surface conductivity becomes negligible. The electrical conductivity of rock cores was found to be in good agreement with the O'Brien theory and the Briggs method. The contribution of the stagnant layer to the surface conductivity in nonaqueous systems has been shown to be significant. This shows that the stagnant layer displays significantly different behavior in different nonaqueous systems, depending on the core porosity and the double-layer overlap. The results indicate that the application of electrokinetics in petroleum reservoirs can provide important insights into reservoir fluid flow characterization. PMID- 17346732 TI - Amplified light scattering and emission of silver and silver core-silica shell particles. AB - Side versus forward light scattergrams, and fluorescence (488 nm excitation) intensity versus particle count histograms were gathered for bare, R6G-coated, and silica-R6G-coated silver particles of 150-200 nm diameter, one-by-one by flow cytometry. Fluorescence emission intensity of the composite particles monotonically increased and then reached a plateau with greater R6G concentrations, as measured by flow cytometry. Fluorescence amplification factors of up to 3.5x10(3) were estimated by reference to measurements on core-shell particles with silica instead of silver cores. Huge surface enhanced Raman scattering (SERS) intensities, at least 10(14)-fold greater than normal Raman scattering intensities, were observed with 633 nm excitation for molecules such as rhodamine 6G (R6G) on the same single particles of silver. Although routine transmission (TEM) and scanning (SEM) electron microscopies showed gross structures of the bare and coated particles, high-resolution field emission scanning electron microscopy (FE-SEM), revealed Brownian roughness describing quantum size and larger structures on the surface of primary colloidal silver particles. These silver particles were further characterized by extinction spectra and zeta potentials. Structural and light scattering observations that are reported herein were used to tentatively propose a new hierarchical model for the mechanism of SERS. PMID- 17346733 TI - Removal of chromate from water by a new CTAB-silica gelatin composite. AB - A novel composite able to remove hexavalent chromium Cr(VI) from aqueous solutions was obtained by adding the silica precursor tetraethoxysilane (TEOS) to the hexadecyltrimethylammonium bromide (CTAB) microemulsion-based gel. A physical characterization of the new matrix revealed high stability of the silica gelatin composite in water at high temperatures and at neutral pH. Good efficiency in removing chromate from neutral solutions was also demonstrated by the adsorption kinetics. In particular, the adsorption data of chromate obtained with the CTAB silica gelatin composite at 25 degrees C and pH 7.5 are described by the Freundlich isotherm model. The specific role of CTAB in the silica gelatin composite was also evaluated by comparing the kinetics of the anionic AOT-silica gelatin composite to the CTAB one. The data collected clearly showed that the positively charged surfactant was necessary to efficiently adsorb Cr(VI) from aqueous solutions. SEM and pulsed gradient spin-echo NMR analysis of the composite demonstrated that the silicon is well assembled in the gelatin network, in which water molecules maintain a high mobility. The diffusion coefficient of water in this system was shown to remain close to the value of pure water. Finally, X-ray analyses of the elemental content in the CTAB-silica gelatin composite indicated no difference in terms of percentage of silica distributions in different areas of the matrix and suggested that chromium adsorption could take place in internal areas. PMID- 17346734 TI - Controllable porous polymer particles generated by electrospraying. AB - In this paper, an electrospraying technique was applied to prepare polycaprolactone (PCL) polymer particles with a different microstructure. The PCL particles can be controlled to have a porous microstructure by tailoring the evaporation of solvents during the electrospraying process. The effect of various concentrations on the morphology and microstructure of PCL particles was investigated. The experiment has demonstrated the versatile capability of the electrohydrodynamic atomization process for preparing polymer PCL porous particles and fibers. The thermally induced and evaporation-induced phase separations are proposed as the main mechanisms for the porous microstructure formation. The results demonstrate that the electrospraying method is a simple, innovative and cost-effective method for preparing polymer particles with controllable microstructures. PMID- 17346735 TI - The effect of step height on the performance of three-dimensional ac electro osmotic microfluidic pumps. AB - Recent numerical and experimental studies have investigated the increase in efficiency of microfluidic ac electro-osmotic pumps by introducing nonplanar geometries with raised steps on the electrodes. In this study, we analyze the effect of the step height on ac electro-osmotic pump performance. AC electro osmotic pumps with three-dimensional electroplated steps are fabricated on glass substrates and pumping velocities of low ionic strength electrolyte solutions are measured systematically using a custom microfluidic device. Numerical simulations predict an improvement in pump performance with increasing step height, at a given frequency and voltage, up to an optimal step height, which qualitatively matches the trend observed in experiment. For a broad range of step heights near the optimum, the observed flow is much faster than with existing planar pumps (at the same voltage and minimum feature size) and in the theoretically predicted direction of the "fluid conveyor belt" mechanism. For small step heights, the experiments also exhibit significant flow reversal at the optimal frequency, which cannot be explained by the theory, although the simulations predict weak flow reversal at higher frequencies due to incomplete charging. These results provide insight to an important parameter for the design of nonplanar electro osmotic pumps and clues to improve the fundamental theory of ACEO. PMID- 17346736 TI - Effect of hydrolyzable metal cations on the coagulation between hexadecane and mineral particles. AB - Mutual coagulation tests were conducted between hexadecane droplets (with and without doping with 0.001 mol/L sodium oleate) and micrometer-sized quartz, kaolinite, and illite particles in the presence and absence of multivalent hydrolyzable metal cations. It was observed that while hexadecane did not coagulate with quartz particles in the entire pH range tested (from 3 to 11), the presence of multivalent metal ions significantly increased the mutual coagulation between the hexadecane and quartz. And this only happened when the pH was raised to the level where first-order metal hydroxyl species and/or metal hydroxides were formed. The implications of this mutual coagulation for bitumen liberation from Alberta oil sands are discussed. PMID- 17346737 TI - Construction of higher-ordered monolayer membranes derived from archaeal membrane lipid-inspired cyclic lipids with longer alkyl chains. AB - A series of artificial cyclic lipids that mimic archaeal membrane ones has been synthesized. The structural features of these molecules include a longer cyclic framework, in which the alkyl chain length ranges from 24 to 32 in carbon number, which is longer than our first analogous molecule with 20-carbon long alkyl chains [K. Miyawaki, T. Takagi, M. Shibakami, Synlett 8 (2002) 1326]. Microscopic observation reveals that these molecules have a self-assembling ability: hydration of the lipids yields multilamellar vesicles in aqueous solution and monolayer sheets on solid supports. High-sensitivity differential scanning calorimetry (24- and 28-carbon alkyl chain lipids) indicates that (i) the alkyl chain length affects their phase behavior and (ii) the enthalpies of endothermic peaks accompanied by phase transition were considerably lower than those of their monomeric phospholipid analogs. Fluorescence polarization measurements suggest that the membranes made from the 24-carbon alkyl chain lipid have a higher polarization factor than membranes composed of DMPC and DMPC plus cholesterol. These findings imply that the cyclic lipids containing 24- and 28-carbon alkyl chain construct well-organized monolayer membranes and, in particular, that the molecular order of the 24-carbon alkyl chain lipid is higher than that of bilayer membranes in the liquid-ordered phase. PMID- 17346738 TI - Synthesis of poly(ethylene glycol) (PEG)-grafted colloidal silica particles with improved stability in aqueous solvents. AB - The known grafting procedures of colloidal silica particles with poly(ethylene glycol) (PEG) lead to grafting layers that detach from the silica surface and dissolve in water within a few days. We present a new grafting procedure of PEG onto silica with a significant improvement of the stability of the grafting layers in aqueous solvents. Moreover, the procedure avoids any dry states or other circumstances leading to strong aggregation of the particles. To achieve the improved water stability, Stober silica particles are first pre-coated with a silane coupling agent (3-aminopropyl)triethoxysilane (APS) to incorporate active amine groups. The water solubility of the pre-coating layer was minimized using a combination of APS with bis-(trimethoxysilylpropyl)amine (BTMOSPA) or bis (triethoxysilyl)ethane (BTEOSE). These pre-coated particles were then reacted with N-succinimidyl ester of mono-methoxy poly(ethylene glycol) carboxylic acid to form PEG-grafted silica particles. The particles form stable dispersions in aqueous solutions as well as several organic solvents. PMID- 17346739 TI - Studies of electrochemical properties of compacted clays by concentration potential method. AB - The development of concentration (membrane) potential upon step-wise change in salt concentration has been studied for diaphragms made of various strongly compacted clays (montmorillonite, illite, kaolinite) equilibrated with 0.1 M NaCl solution. Porous ceramic filters were used to confine the clays mechanically to be able to achieve high extent of compaction (dry density approximately 2000 kg/m3). A theoretical analysis has revealed that the relaxation pattern is primarily controlled by the properties of porous filters and only slightly depends on the clay properties. At the same time, quasi-stationary values of concentration potential are directly related to the electrochemical perm selectivity of clay. This property has revealed considerable differences in the electrochemical behaviour of various clays used in this study. This has been attributed to the differences in the micro-structure of clays, in particular to the existence or nonexistence of the so-called interlayer water where cations may retain some mobility. It has also been shown that in clays with high electrochemical perm-selectivity, one can expect a strong increase in the diffusivity of cationic radio-tracers with decreasing ionic strength of equilibrium electrolyte solution. At the same time, low electrochemical perm selectivity means no noticeable dependence of this kind. The correctness of this observation has been corroborated by the comparison of our findings with the literature data on the diffusion of cationic radio-tracers through compacted montmorillonite (high perm-selectivity) and kaolinite (low perm-selectivity). To check the self-consistency of our approach, we have also carried out sample measurements of diffusion of cationic and anionic radio-tracers through compacted illite. It has been found that the measured effective diffusion coefficients were in excellent agreement with the electrochemical perm-selectivity estimated for this clay from the measurements of concentration potential. PMID- 17346740 TI - Young children's reports of when learning occurred. AB - This study investigated young children's reports of when learning occurred. A total of 96 4-, 5-, and 6-year-olds were recruited from suburban preschools and elementary schools. The children learned an animal fact and a body movement. A week later, children learned another animal fact and another body movement and then answered questions about when the different learning events occurred. Responses of children who responded correctly to control questions about time supported the hypothesis that temporal distance questions would elicit more correct responses than would temporal location questions. Partial support was also found for the hypothesis that behavior learning would generate more correct reports than would fact learning. Implications for characterizations of children's developing understanding of knowledge and for applications of those characterizations in education and eyewitness testimony are discussed. PMID- 17346741 TI - A fluorometric quantitative erythrophagocytosis assay using human THP-1 monocytic cells and PKH26-labelled red blood cells. AB - Removal of senescent, damaged or diseased red blood cells (RBCs) from the circulation in vivo occurs by a process known as erythrophagocytosis. The exact details of the signaling mechanisms that mark RBCs for recognition and influence erythrophagocytosis are still not completely understood. The aim of this study was to develop a quantitative, fluorometric erythrophagocytosis assay for human RBCs and phagocytes to aid elucidation of the biological mechanisms regulating erythrophagocytosis. RBCs were labelled with the lipophilic fluorescent dye PKH26 and incubated with the human monocytic cell line THP-1 at 37 degrees C for 45 min. Non-phagocytosed RBCs were lysed with hypotonic saline. Phagocytosed PKH26 labelled RBCs within THP-1 cells were detected with a fluorescence plate-reader and quantitated using a standard curve of known numbers of PKH26-labelled RBCs. Assay conditions were optimised for the numbers of phagocytes and RBCs, incubation time and fluorescence excitation and emission wavelengths. Erythrophagocytosis was also assessed by flow cytometry to determine the proportion of THP-1 cells with ingested RBCs and showed good correlation (P=0.7) between the two methods. The quantitative, fluorometric plate assay is very sensitive and has good reproducibility, making it a useful tool to investigate the biological mechanisms that regulate erythrophagocytosis of normal and diseased RBCs. PMID- 17346742 TI - NADPH oxidase-dependent redox signaling in human heart failure: relationship between the left and right ventricle. AB - Oxidative stress resulting from increased superoxide generation by NADPH oxidase is implicated in the pathophysiology of human heart failure. Downstream targets of NADPH oxidase remain undefined and available information is restricted to the left ventricle (LV). Thus, we aimed to assess the cascade of events triggered by increased NADPH oxidase activity (lipid peroxidation and activation of mitogen activated protein kinases ERK1/2, JNK and p38) and their mutual relationship in right (RV) and (LV) of end-stage failing human hearts. When compared to control ventricles, diseased RV and LV showed a significant increase in NADPH oxidase superoxide production that positively correlated with p47(phox) membrane translocation (RV: r=0.76, P<0.001; LV: r=0.79, P<0.001). MDA content, a marker of lipid peroxidation, was also enhanced and ERK and p38, but not JNK, were activated. For all these relevant steps of the oxidative stress pathway, a significant correlation was observed between LV and RV from the same heart (NADPH dependent superoxide production: r=0.678, P<0.0055; MDA: r=0.95, P<0.0001; p p38/p38 ratio: r=0.926, P<0.0001; p-ERK/ERK ratio: r=0.913, P<0.0001). We concluded that in human heart failure, both ventricles are targets of NADPH oxidase superoxide generation which in turn may trigger the coordinated activation of downstream signaling components. This pathway may contribute to adverse remodeling of the LV and RV and subsequent progression toward end-stage heart failure, suggestive of new therapeutic targeting strategy. PMID- 17346743 TI - Multiple origins of replication contribute to a discontinuous pattern of DNA synthesis across the T4 genome during infection. AB - Chromosomes provide a template for a number of DNA transactions, including replication and transcription, but the dynamic interplay between these activities is poorly understood at the genomic level. The bacteriophage T4 has long served as a model for the study of DNA replication, transcription, and recombination, and should be an excellent model organism in which to integrate in vitro biochemistry into a chromosomal context. As a first step in characterizing the dynamics of chromosomal transactions during T4 infection, we have employed a unique set of macro array strategies to identify the origins of viral DNA synthesis and monitor the actual accumulation of nascent DNA across the genome in real time. We show that T4 DNA synthesis originates from at least five discrete loci within a single population of infected cells, near oriA, oriC, oriE, oriF, and oriG, the first direct evidence of multiple, active origins within a single population of infected cells. Although early T4 DNA replication is initiated at defined origins, continued synthesis requires viral recombination. The relationship between these two modes of replication during infection has not been well understood, but we observe that the switch between origin and recombination mediated replication is dependent on the number of infecting viruses. Finally, we demonstrate that the nascent DNAs produced from origin loci are regulated spatially and temporally, leading to the accumulation of multiple, short DNAs near the origins, which are presumably used to prime subsequent recombination mediated replication. These results provide the foundation for the future characterization of the molecular dynamics that contribute to T4 genome function and evolution and may provide insights into the replication of other multi origin chromosomes. PMID- 17346744 TI - A molecular clock operates during chick autopod proximal-distal outgrowth. AB - Temporal control can be considered the fourth dimension in embryonic development. The identification of the somitogenesis molecular clock provided new insight into how embryonic cells measure time. We provide the first evidence of a molecular clock operating during chick fore-limb autopod outgrowth and patterning, by showing that the expression of the somitogenesis clock component hairy2 cycles in autopod chondrogenic precursor cells with a 6 h periodicity. We determined the length of time required to form an autopod skeletal limb element, and established a correlation between the latter and the periodicity of cyclic hairy2 gene expression. We suggest that temporal control exerted by cyclic gene expression can be a widespread mechanism providing cellular temporal information during vertebrate embryonic development. PMID- 17346745 TI - Defining the interacting regions between apomyoglobin and lipid membrane by hydrogen/deuterium exchange coupled to mass spectrometry. AB - Sperm whale myoglobin can be considered as the model protein of the globin family. The pH-dependence of the interactions of apomyoglobin with lipid bilayers shares some similarities with the behavior of pore-forming domains of bacterial toxins belonging also to the globin family. Two different states of apomyoglobin bound to a lipid bilayer have been characterized by using hydrogen/deuterium exchange experiments and mass spectrometry. When bound to the membrane at pH 5.5, apomyoglobin remains mostly native-like and interacts through alpha-helix A. At pH 4, the binding is related to the stabilization of a partially folded state. In that case, alpha-helices A and G are involved in the interaction. At this pH, alpha-helix G, which is the most hydrophobic region of apomyoglobin, is available for interaction with the lipid bilayer because of the loss of the tertiary structure. Our results show the feasibility of such experiments and their potential for the characterization of various membrane-bound states of amphitropic proteins such as pore-forming domains of bacterial toxins. This is not possible with other high-resolution methods, because these proteins are usually in partially folded states when interacting with membranes. PMID- 17346746 TI - Crowded surfaces change annealing dynamics of actin filaments. AB - Changes in cell shape that occur in many cellular processes are thought to arise from polymerization of actin filaments near the cell membrane. End-to-end annealing of actin filaments is believed to play only a minor role in this process, as annealing in solution was shown to be a slow process, which is not typical for a bimolecular reaction, its rate constant decreasing over time, being inversely proportional to the filament length. Furthermore, in vitro studies on f actin solutions were found to display an exponential steady-state length distribution. In the cell, many physiologically important parameters, such as mechanical strength or viscoelastic response are a direct function of the physical properties of the underlying actin cytoskeleton, such as actin filament length distribution and dynamics. How the underlying physical parameters of the actin cytoskeleton may be influenced by the cell surface or molecular crowding remains poorly understood. Using total internal reflection fluorescence (TIRF) microscopy we reinvestigated actin end-to-end annealing in vitro in a more realistic environment. We studied the process near a hydrophilic surface together with crowding agents, in order to mimic the physiological media near the cell membrane, which has substantial amounts of macromolecules present. We find that actin end-to-end annealing changes in three ways near a crowded hydrophilic surface as compared to solution. First the annealing rate becomes a factor of 20 faster than in solution. Second the rate of annealing becomes typical of a bimolecular reaction, shows no length dependence and is basically just a function of the square of the concentration of ends. Lastly the length distribution is Gaussian throughout the entire annealing process. This implicates that dynamic rearrangement of actin filaments by annealing near the leading edge of the cell, could change physical parameters like the mechanical response and contribute significantly to cell motility. PMID- 17346747 TI - The natural history of relapses in multiple sclerosis. AB - Relapses are a defining feature of multiple sclerosis (MS), serving as the basis for categorizing the different phases of the disease, and providing a means of measuring treatment success, following disease activity, and defining prognostic features. While the dissociation between relapses and disease progression indicates the boundaries of relapse history in determining disease course over time, it also highlights the importance of relapses to overall disease evolution. A broad understanding of relapse definition and dynamics is important to promote accurate diagnosis, patient management, and treatment decisions. In an attempt to describe the underlying etiology and clinical impact of relapses in MS, this review will examine relapse findings from natural history studies, the utility of relapse as a predictor of disease course, the factors that may contribute to relapse, and data on relapse resolution. The relationship of clinical relapses to MRI disease activity and to the onset of progressive disease will also be addressed. PMID- 17346748 TI - MRI relapses have significant pathologic and clinical implications in multiple sclerosis. AB - MRI is extremely sensitive for detecting new inflammatory activity in the central nervous system of patients with multiple sclerosis (MS) that is often clinically silent. Each new lesion often leaves a permanent MS plaque, which is composed of varying degrees of demyelination, axonal loss, and gliosis. New large lesions have a greater risk of evolving into permanent T1-weighted hypointense lesions (black holes) that pathologically contain the greatest axonal loss and correlate more strongly with clinical disability than with overall lesion load on T2 weighted images. There is also an association between the severity of the total T2 lesion burden with cerebral atrophy and with diffuse changes in the normal appearing brain tissue as determined by magnetization transfer imaging and magnetic resonance spectroscopy. To maintain normal clinical functioning, the brain may compensate by recruiting increased regions of cortex, as demonstrated by functional MRI (fMRI) studies. The degree of increased fMRI activation is proportional to the severity of T2 lesion load, up to a critical limit at which it appears that these compensatory mechanisms may fail. Therefore, new inflammatory activity, as detected by MRI, carries a risk of significant early pathologic damage and delayed yet permanent clinical disability. PMID- 17346749 TI - Evidence for astrocytosis in ALS demonstrated by [11C](L)-deprenyl-D2 PET. AB - OBJECTIVE: To use deuterium-substituted [11C](L)-deprenyl PET to depict astrocytosis in vivo in patients with amyotrophic lateral sclerosis (ALS). BACKGROUND: In human brain, the enzyme MAO-B is primarily located in astrocytes. L-deprenyl binds to MAO-B and autoradiography with 3H-L-deprenyl has been used to map astrocytosis in vitro. Motor neuron loss in ALS is accompanied by astrocytosis and astrocytes may play an active role in the neurodegenerative process. Deuterium-substituted [11C](L)-deprenyl PET provides an opportunity to localize astrocytosis in vivo in the brain of patients with ALS. METHODS: Deuterium-substituted [11C](L)-deprenyl PET was performed in seven patients with ALS and seven healthy control subjects. RESULTS: Increased uptake rate of [11C](L)-deprenyl was demonstrated in ALS in pons and white matter. CONCLUSION: This study provides evidence that astrocytosis may be detected in vivo in ALS by the use of deuterium-substituted [11C](L)-deprenyl PET though further studies are needed to determine whether deuterium-substituted [11C](L)-deprenyl binding tracks disease progression and reflects astrocytosis. PMID- 17346750 TI - Phosphatidylinositol-3-kinase is involved in the antihyperglycemic effect induced by resveratrol in streptozotocin-induced diabetic rats. AB - Resveratrol, a polyphenolic substance found in grape skin, is proposed to account in part for the protective effect of red wine in the cardiovascular system. The aim of the present study is to investigate the action and possible mechanisms of resveratrol-produced regulation of plasma glucose in normal and diabetic rats including the animal model of streptozotocin (STZ)-induced and nicotinamide-STZ induced (NA-STZ), and insulin-resistant diabetic rats. Resveratrol (p.o.) produced a hypoglycemic effect in a dose-dependent manner in normal and diabetic rats, and the insulin level was increased following resveratrol treatment in normal and NA-STZ diabetic rats. In insulin-deficient STZ-diabetic rats, resveratrol significantly lowered the plasma glucose 90 min after oral treatment, and the hypoglycemic effect was abolished by phosphatidyl-3-kinase (PI3K) inhibitors (LY294002 and wortmannin) which also inhibited resveratrol-induced Akt phosphorylation in soleus muscle of STZ-diabetic rats. The change in the protein expression level of glucose transporter subtype 4 (GLUT4) in the soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats treated with resveratrol (3 mg/kg, p.o.) for 7 days was examined. Resveratrol normalized hepatic PEPCK expression and increased GLUT4 expression in the soleus muscle of STZ-diabetic rats. The results indicate that the mechanisms contributing to the hypoglycemic effect of resveratrol include insulin-dependent and insulin-independent pathway, and PI3K-Akt-signaling was involved in the latter mechanism to enhance glucose uptake in skeletal muscle. PMID- 17346751 TI - Induction of reactive oxygen species from isolated rat glomeruli by protein kinase C activation and TNF-alpha stimulation, and effects of a phosphodiesterase inhibitor. AB - Diabetic nephropathy is a major complication of diabetes leading to end-stage renal disease, which requires hemodialysis. Although the mechanism by which it progresses is largely unknown, the role of hyperglycemia-derived oxidative stress has recently been the focus of attention as the cause of diabetic complications. Constituent cells of the renal glomeruli have the capacity to release reactive oxygen species (ROS) upon stimulation of NADPH oxidase activated by protein kinase C (PKC). Hyperglycemia and insulin resistance in the diabetic state are often associated with activation of PKC and tumor necrosis factor (TNF)-alpha, respectively. The aim of this study is to clarify the signaling pathway leading to ROS production by PKC and TNF-alpha in rat glomeruli. Isolated rat glomeruli were stimulated with phorbol 12-myristate 13-acetate (PMA) and TNF-alpha, and the amount of ROS was measured using a chemiluminescence method. Stimulation with PMA (10 ng/ml) generated ROS with a peak value of 136+/-1.2 cpm/mg protein (mean+/ SEM). The PKC inhibitor H-7, the NADPH oxidase inhibitor diphenylene iodonium and the phosphatidylinositol-3 (PI-3) kinase inhibitor wortmannin inhibited PMA induced ROS production by 100%, 100% and 80%, respectively. In addition, TNF alpha stimulated ROS production (283+/-5.8/mg protein/20 min). The phosphodiesterase inhibitor cilostazol activates protein kinase A and is reported to improve albuminuria in diabetic rats. Cilostazol (100 microg/ml) inhibited PMA, and TNF-alpha-induced ROS production by 78+/-1.8, and 19+/-2.7%, respectively. The effects of cilostazol were not additive with wortmannin. Cilostazol arrests oxidative stress induced by PKC activation by inhibiting the PI-3 kinase-dependent pathway, and may thus prevent the development of diabetic nephropathy. PMID- 17346752 TI - Glycyrrhizin protection against 3-morpholinosydnonime-induced mitochondrial dysfunction and cell death in lung epithelial cells. AB - The present study was designed to assess the preventive effect of licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid against mitochondrial damage and cell death in lung epithelial cells exposed to 3-morpholinosydnonime, a donor of nitric oxide and superoxide. Treatment of lung epithelial cells with 3 morpholinosydnonime resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH. Treatment of glycyrrhizin and 18beta-glycyrrhetinic acid attenuated the 3 morpholinosydnonime-induced mitochondrial damage, formation of reactive oxygen species and GSH depletion and revealed a maximal inhibitory effect at 10 and 1 muM, respectively; beyond these concentrations the inhibitory effect declined. Melatonin, carboxy-PTIO, rutin and uric acid reduced the 3-morpholinosydnonime induced cell death. The results show that glycyrrhizin and 18beta-glycyrrhetinic acid seem to prevent the toxic effect of 3-morpholinosydnonime against lung epithelial cells by suppressing the mitochondrial permeability transition that leads to the release of cytochrome c and activation of caspase-3. The preventive effect may be ascribed to the inhibitory action on the formation of reactive oxygen species and depletion of GSH. The findings suggest that licorice compounds seem to prevent the nitrogen species-mediated lung cell damage. PMID- 17346753 TI - Dysfunction of the non-neuronal cholinergic system in the airways and blood cells of patients with cystic fibrosis. AB - The non-neuronal cholinergic system is widely expressed in human airways, skin and immune cells. Choline acetyltransferase (ChAT), acetylcholine and nicotine/muscarine receptors are demonstrated in epithelial surface cells, submucosal glands, airway smooth muscle fibres and immune cells. Moreover, acetylcholine is involved in the regulation of cell functions like proliferation, differentiation, migration, organization of the cytoskeleton, cell-cell contact, secretion and transport of ions and water. Cystic fibrosis (CF), the most frequent genetic disorder, is known to be caused by a mutation of the CF-gene coding for the cystic fibrosis transmembrane regulator protein (CFTR). CFTR represents a regulating transport protein for ion channels and processes involving endo- and exocytosis. Despite the identification of the genetic mutation knowledge of the underlying cellular pathways is limited. In the present experiments the cholinergic system was investigated in the peripheral blood and in the lung of CF patients undergoing lung transplantation (n=7). Acetylcholine content in bronchi and lung parenchyma of CF was reduced by 70% compared to controls (tumor-free tissue obtained from patients with lung tumor; n=13). In contrast, ChAT activity was elevated to some extent (p>0.05) in CF, and esterase activity did not differ from control. Acetylcholine content extracted from peripheral leucocytes (30 ml) was also reduced by 70% in CF (n=13) compared to healthy volunteers (n=9). Double labelling experiments with anti-CF antibodies and anti-ChAT antibodies showed a co-localization in peripheral lymphocytes, giving first evidence that CFTR may be linked with the intracellular storage/transport of non-neuronal acetylcholine. It is concluded that the non neuronal cholinergic system is involved in the pathogenesis of CF. A reduced content of non-neuronal acetylcholine could contribute to the deleterious changes of epithelial ion and water movements in CF, because acetylcholine stimulates apical Cl(-) secretion, inhibits apical Na(+) and water absorption and therewith facilitates mucociliary clearance. PMID- 17346754 TI - The M4 muscarinic acetylcholine receptor plays a key role in the control of murine hair follicle cycling and pigmentation. AB - Cholinergic receptors of the muscarinic class (M1-M5) are expressed in epidermal keratinocytes and melanocytes as well as in the hair follicle. Knockout (KO) mice of all five receptors have been created and resulted in different phenotypes. KO mice with a deletion of the M4 muscarinic acetylcholine receptor (M4R) present a striking hair phenotype, which we have analyzed here in greater detail by quantitative histomorphometry. Earlier studies revealed a retarded hair follicle morphogenesis in M4R KO mice, compared to age-matched wild type controls. On day 17, when mice enter the first hair growth cycle, the KO mice still showed a slightly retarded catagen phase. Subsequently, hair follicles of the KO mice stayed in a highly significantly prolonged telogen phase, while wild type mice had already far progressed in the hair cycle by entry into anagen. Most strikingly, the M4R KO mice did not engage in follicular melanogenesis and failed to produce pigmented hair shafts. The current pilot study suggests that the M4R plays a fundamental role in the control of the murine hair follicle cycling and is an essential signaling element in the control of hair follicle pigmentation. PMID- 17346755 TI - Taxonomic sufficiency for soft-bottom sublittoral mollusks assemblages in a tropical estuary, Guanabara Bay, Southeast Brazil. AB - Guanabara Bay (GB) is considered to be one of the most polluted environments of the southern Brazilian coastline. This typical estuarine system is impacted by the heavy discharge of both industrial and domestic waste from the Rio de Janeiro metropolitan area. The mollusc community structure and distribution was investigated between 2000 and 2001, using a three month sampling design of 38 stations, according to austral seasons. Species abundance was aggregated into progressively higher taxa matrices (genus, family, order) and were analysed using multivariate techniques. Mollusc distribution in GB varied significantly in space and time and was probably ruled by the organic enrichment effects of hypoxia and altered redox conditions coupled with prevailing patterns of circulation. Within the sectors of GB an increasing gradient in mollusc diversity and occurrence was observed, ranging from the azoic and impoverished stations in the inner sector to a well-structured community in terms of species composition and abundance inhabiting the outer sector. The non-metric multidimensional scaling (nMDS) and cluster analysis showed similar results when species were aggregated into genera and families, while greater difference occurred at coarser taxonomic identification (order). The literature about taxonomic sufficiency has demonstrated that faunal patterns at different taxonomic levels tend to become similar with increased pollution. In Guanabara Bay, an analysis carried out solely at family level is perfectly adequate to describe the ecophysiological stress. Further aggregation to order level changed the perceived patterns of differences. However, a different taxonomic resolution can be chosen depending on the type of ecological patterns investigated. PMID- 17346756 TI - Seasonal and tidal variability of phosphorus along a salinity gradient in the heavily polluted estuarine system of Santos/Sao Vicente - Sao Paulo, Brazil. PMID- 17346757 TI - A site to remember: H3K36 methylation a mark for histone deacetylation. AB - Chromatin structure exerts vital control over gene expression, DNA replication, recombination, and repair. In addition to altering RNA polymerase II's (Pol II) accessibility to DNA, histones are involved in the recruitment of activator and repressor complex(es) to regulate gene expression. Histone deacetylase Rpd3 exists in two distinct forms, Rpd3S and Rpd3L. Several recent studies demonstrated that the Eaf3 chromodomain, an Rpd3S subunit, recognizes Set2 methylated histone H3K36, initiating Rpd3 deacetylase activity in the wake of transcribing Pol II. Eaf3 and Set2 inhibit internal initiation within mRNA coding regions, similar to the transcription elongation factor and histone chaperone, FACT. Recent studies reviewed here demonstrate that histone deacetylation on the body of a transcribed gene is regulated via Set2-mediated methylation of histone H3-K36. These modifications provide restoration of normal chromatin structure in the wake of elongating Pol II and prevent inappropriate initiation within protein coding regions masked by chromatin. PMID- 17346758 TI - Reinforcer-specificity of appetitive and consummatory behavior of rats after Pavlovian conditioning with food reinforcers. AB - We examined the reinforcer-specificity of Pavlovian conditioning in the control of appetitive and consummatory behaviors in Pavlovian-to-instrumental transfer, cue-potentiated eating, and devaluation procedures. Rats received pairings of one conditioned stimulus with sucrose and another conditioned stimulus with maltodextrin. In Experiment 1, rats were also trained to earn sucrose for one instrumental response and maltodextrin for another. In a transfer test, the Pavlovian cues enhanced the rate of instrumental responding more when the food reinforcer predicted by the instrumental response and the Pavlovian cue were consistent than when they were inconsistent, but both cues enhanced both responses. In Experiment 2, sated rats' consumption of each food was potentiated in the presence of a cue for that food, but not in the presence of a cue for the other food. In Experiment 3, one food was devalued by pairing it with lithium chloride, prior to testing food consumption and food-cup directed behaviors. The food cues selectively controlled food-cup related behaviors, regardless of the presence of the devalued or nondevalued foods in the food cup. Together, these results are consistent with the view that conditioned cues modulate appetitive and consummatory behaviors with increasing levels of specificity. The closer an action comes to ingestion, the more it is controlled by sensory properties conveyed by learned cues. These data are discussed in the context of allostatic regulation of food foraging and intake. PMID- 17346759 TI - Loline alkaloids: Currencies of mutualism. AB - Several species of Lolium and other cool-season grasses (Poaceae subfamily Pooideae) tend to harbor symbiotic, seed-transmitted, fungi that enhance their fitness by various means. These fungal endophytes--species of Neotyphodium or Epichloe (Clavicipitaceae)--are known for production of antiherbivore metabolites such as the bioprotective loline alkaloids. Lolines are saturated pyrrolizidines with an exo-1-amine and an ether bridge between C-2 and C-7. The ether bridge is an unusual feature for a biogenic compound in that it links two bridgehead carbon atoms. Much of the loline-biosynthetic pathway has been elucidated by administering isotopically labeled precursors to fungal cultures and by comparisons of loline biosynthesis genes to known gene families. The first step appears to be an unusual gamma-substitution reaction involving an enzyme related to O-acetylhomoserine (thiol) lyase, but which uses the secondary amine of L proline rather than a sulfhydryl group as the nucleophile. The strained ether bridge is added after formation of the pyrrolizidine rings. Lolines with dimethylated or acylated 1-amines have insect antifeedant and insecticidal activities comparable to nicotine, but little or no toxicity to mammals. Considering the surprising abundance of lolines in some grass-endophyte symbiota, possible additional effects on plant stress tolerance and physiology are worth future consideration. In this review, we discuss the history of loline discovery, methods of analysis, biological activities and distribution in nature, as well as progress on the genetics and biochemistry of their biosynthesis, and on the chemical synthesis of these alkaloids. PMID- 17346760 TI - When and why do non-neutral metacommunities appear neutral? AB - Hubbell's neutral theory assumes that all species in a community have the same per capita fitness. Despite the overwhelming evidence against this assumption in most communities the neutral theory has often been, though not always, successful at predicting patterns of diversity in nature. I analyze a non-neutral model in order to suggest conditions under which observed species-abundance distributions (SADs) could be expected to resemble neutral distributions. The non-neutral model consists of two guilds of species such that (1) individuals between guilds do not interact, (2) dynamics within guilds follow Hubbell's model and (3) neutral parameters between guilds differ. This two-guild model generates SADs that appear neutral in some cases and clearly non-neutral in other cases. This result suggests that SADs may be more informative about niche structure than previously thought. The two-guild model could be tested in communities composed of fairly well-defined guilds or functional groups. PMID- 17346761 TI - Expression and characterization of a recombinant fibrinogenolytic serine protease from green pit viper (Trimeresurus albolabris) venom. AB - Viper venom serine proteases (SPs) display several effects on hemostatic system. Molecular cloning showed that Trimeresurus albolabris venom comprised a mixture of five SPs with thrombin-like (2), fibrinogenase (2) and plasminogen-activating (1) activities. Because only few fibrinogenolytic SP sequences were reported, we decided to express albofibrase, a novel fibrinogenase from T. albolabris using Pichia pastoris system. The recombinant active form of enzyme was 30 kDa including 2.2 kDa of glycosylation. Albofibrase showed an alpha fibrinogenase activity. In addition, a plasminogen activating and clotting effect were detectable. Albofibrase prolonged APTT and PT in a time-dependent manner. The effect was neutralized by pre-incubation with equine antivenom to T. albolabris. Therefore, the protein is potentially useful as a new anticoagulant as the antidote is clinically available. Sequence analysis compared with other snake venom fibrinogenases and SPs could not find any unique residues responsible for their various effects. Structure-function relationship should be further studied using mutagenesis in order to explore the mechanisms of venom protease functional diversity. PMID- 17346762 TI - Involvement of UL24 in herpes-simplex-virus-1-induced dispersal of nucleolin. AB - UL24 of herpes simplex virus 1 is important for efficient viral replication, but its function is unknown. We generated a recombinant virus, vHA-UL24, encoding UL24 with an N-terminal hemagglutinin tag. By indirect immunofluorescence at 9 h post-infection (hpi), we detected HA-UL24 in nuclear foci and in cytoplasmic speckles. HA-UL24 partially co-localized with nucleolin, but not with ICP8 or coilin, markers for nucleoli, viral replication compartments, and Cajal bodies respectively. HA-UL24 staining was often juxtaposed to that of another nucleolar protein, fibrillarin. Analysis of HSV-1-induced nucleolar modifications revealed that by 18 hpi, nucleolin staining had dispersed, and fibrillarin staining went from clusters of small spots to a few separate but prominent spots. Fibrillarin redistribution appeared to be independent of UL24. In contrast, cells infected with a UL24-deficient virus retained foci of nucleolin staining. Our results demonstrate involvement of UL24 in dispersal of nucleolin during infection. PMID- 17346764 TI - Characterization of activated sludge exocellular polymers using several cation associated extraction methods. AB - Evaluation of prior research and preliminary investigations in our laboratory led to the development of an extraction strategy that can be used to target different cations in activated sludge floc and extract their associated extracellular polymeric substances (EPS). The methods we used were the cation exchange resin (CER) procedure, base extraction, and sulfide addition to extract EPS linked with divalent cations, Al, and Fe, respectively. A comparison of sludge cations before and after CER extraction revealed that most of Ca(2+) and Mg(2+) were removed while Fe and Al remained intact, suggesting that this method is highly selective for Ca(2+) and Mg(2+)-bound EPS. The correlation between sludge Fe and sulfide extracted EPS was indicative of selectivity of this method for Fe-bound EPS. The base extraction was less specific than the other methods but it was the method releasing the largest amount of Al into the extract, indicating that the method extracted Al-bound EPS. Concomitantly, the composition of extracted EPS and the amino acid composition differed for the three methods, indicating that EPS associated with different metals were not the same. The change in EPS following anaerobic and aerobic digestion was also characterized by the three extraction methods. CER-extracted EPS were reduced after aerobic digestion while they changed little by anaerobic digestion. On the other hand, anaerobic digestion was associated with the decrease in sulfide-extracted EPS. These results suggest that different types of cation-EPS binding mechanisms exist in activated sludge and that each cation-associated EPS fraction imparts unique digestion characteristics to activated sludge. PMID- 17346763 TI - Linking impulse response functions to reaction time: rod and cone reaction time data and a computational model. AB - Reaction times for incremental and decremental stimuli were measured at five suprathreshold contrasts for six retinal illuminance levels where rods alone (0.002-0.2 Trolands), rods and cones (2-20 Trolands) or cones alone (200 Trolands) mediated detection. A 4-primary photostimulator allowed independent control of rod or cone excitations. This is the first report of reaction times to isolated rod or cone stimuli at mesopic light levels under the same adaptation conditions. The main findings are: (1) For rods, responses to decrements were faster than increments, but cone reaction times were closely similar. (2) At light levels where both systems were functional, rod reaction times were approximately 20 ms longer. The data were fitted with a computational model that incorporates rod and cone impulse response functions and a stimulus-dependent neural sensory component that triggers a motor response. Rod and cone impulse response functions were derived from published psychophysical two-pulse threshold data and temporal modulation transfer functions. The model fits were accomplished with a limited number of free parameters: two global parameters to estimate the irreducible minimum reaction time for each receptor type, and one local parameter for each reaction time versus contrast function. This is the first model to provide a neural basis for the variation in reaction time with retinal illuminance, stimulus contrast, stimulus polarity, and receptor class modulated. PMID- 17346765 TI - Validation of host-specific Bacteriodales 16S rRNA genes as markers to determine the origin of faecal pollution in Atlantic Rim countries of the European Union. AB - The recent implementation of the Revised Bathing Water Directive in the European Union has highlighted the need for development of effective methods to differentiate between sources of faecal contamination. It had previously been shown that amplification of 16S rRNA genes of host-specific Bacteriodales species using the HF183F and CF128F primers could be used as markers for human and bovine faecal contamination in the United States. This paper determined the sensitivity and specificity of these markers in four Atlantic Rim countries (France, Ireland, Portugal and the United Kingdom) to evaluate their usefulness in determining the origin of faecal contamination. It was shown that the HF183F marker displayed high sensitivity (80-100%) and specificity (91-100%), and is reliable as an indication of human faecal contamination. The CF128F marker displayed 100% sensitivity in all four countries. However, strong regional variations in specificity (41-96%) were observed, highlighting the need for local validation before this marker is employed in source tracking of faecal contamination. PMID- 17346766 TI - Interplay of different NOM fouling mechanisms during ultrafiltration for drinking water production. AB - Ultrafiltration is an emerging technology for drinking water production, but a main challenge remains the lack of understanding about fouling. This paper investigates the impact of molecular interactions between different natural organic matter (NOM) compounds on ultrafiltration fouling mechanisms. We performed dead-end filtration experiments with individual and mixed humic acid and alginate (polysaccharide). Alginate showed detrimental, but mostly reversible, flux decline and high solute retention. Our results indicate that this was caused by pore blocking transformed into cake building and weak molecular foulant-membrane and foulant-foulant interactions. In the presence of calcium, aggravated fouling was observed, related to complexation of alginate and its subsequently induced gel formation. With humic acid, more severe irreversible fouling occurred due to humic acid adsorption. Minor adsorption of alginate onto the membrane was also observed, which probably caused the substantial irreversible flux decline. The fouling characteristics in the mixtures reflected a combination of the individual humic acid and alginate experiments and we conclude, that the individual fouling mechanisms mutually influence each other. A model elucidates this interplay of the individual fouling mechanisms via hydrophobic and electrostatic interactions. In our study such an interplay resulted in an alginate cake, or gel in the presence of calcium, which is relatively irreversibly adsorbed onto the membrane by humic acid associations. This study shows the importance of mutual influences between various foulants for improved understanding of fouling phenomena. Furthermore it shows that substances with a minor individual influence might have a large impact in mixed systems such as natural water. PMID- 17346767 TI - Transport of Escherichia coli in saturated porous media: dual mode deposition and intra-population heterogeneity. AB - Because of heterogeneity among members of a bacteria population, deposition rates of bacteria may decrease upon the distance bacteria are transported in an aquifer. Such deposition rate decreases may result in retained bacteria concentrations, which decrease hyper-exponentially as a function of transport distance, and may therefore significantly affect the transport of colloids in aquifers. We investigated the occurrence of hyper-exponential deposition of Escherichia coli, an important indicator for fecal contamination, and the causes for such behavior. In a series of column experiments with glass beads of various sizes, we found that attachment of E. coli decreased hyper-exponentially, or, on logarithmic scale in a bimodal way, as a function of the transported distance from the column inlet. From data fitting of the retained bacteria concentration profiles, the sticking efficiency of 40% of the E. coli population was high (alpha=1), while the sticking efficiency of 60% was low (alpha=0.01). From the E. coli total population, an E. coli subpopulation consisting of slow attachers could be isolated by means of column passage. In subsequent column experiments this subpopulation attached less than the E. coli total population, consisting of both slow and fast attachers. We concluded that the main driver for the observed dual mode deposition was heterogeneity among members of the bacteria population. Intra-population may result in some microbes traveling surprisingly high distances in the subsurface. Extending the colloid filtration theory with intra population variability may provide a valuable framework for assessing the transport of bacteria in aquifers. PMID- 17346768 TI - Comparison of control strategies for nitrogen removal in an activated sludge process in terms of operating costs: a simulation study. AB - In this paper several control strategies for nitrogen removal are proposed and evaluated in a benchmark simulation model of an activated sludge process. The goal is to determine which control strategy delivers better performance with respect to plant operating costs. In the study, constant manipulated variables and various PI and feedforward control strategies are tested and compared with predictive control, which uses an ideal process model. The control strategies differ in the information used about the process (number of sensors and sensor location) and in the complexity of the control algorithms. To determine the set points that yield optimal operating costs, an operational map is constructed for each control strategy. Results of the simulation show that with PI and feedforward controllers almost the same optimal operating costs can be achieved as with more advanced MPC algorithms under various plant operating conditions. More advanced control algorithms are advantageous only in cases where the plant is highly loaded and if stringent effluent fines are imposed by legislation. PMID- 17346769 TI - Physiological and biochemical responses to high Mn concentrations in two contrasting Populus cathayana populations. AB - We exposed the cuttings of Populus cathayana to Hoagland's solution containing four different manganese (Mn) concentrations (0, 0.1, 0.5 and 1mM) in a greenhouse to characterize the physiological and biochemical basis of Mn resistance in woody plants. Two contrasting populations of P. cathayana were used in our study, which were from the wet and dry climate regions in western China, respectively. The results showed that Mn treatments significantly decreased chlorophyll content and growth characteristics, including shoot height, basal diameter, biomass accumulation and total leaf area in the two populations. Mn treatments also significantly increased the levels of abscisic acid (ABA), polyamines and free amino acids especially proline (Pro), histidine (His) and phenylalanine (Phe) available for cellular signaling and heavy metal chelation. In addition, high Mn concentrations also caused oxidative stress indicated as the accumulation of hydrogen peroxide (H(2)O(2)) and malondialdehyde (MDA) contents. On the other hand, there were different responses to Mn stress between the two contrasting populations. Compared with the dry climate population, the wet climate population accumulated more Mn in plant tissues especially in leaves; it showed lower tolerance index and more pronounced decrease in growth and chlorophyll contents. The wet climate population not only accumulated less ABA, putrescine and free amino acids, but also exhibited lower activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX), thus suffering from more serious oxidative damage. Therefore, our results showed that the wet climate population was more susceptible to Mn stress than the dry climate population. PMID- 17346770 TI - Dioxins in human milk and smoking of mothers. AB - BACKGROUND: The relation between the levels of dioxins in human breast milk and the smoking habits of the mothers is controversial. To clarify this relationship, we analyzed data from the human milk survey in Japan. METHODS: The human milk survey has been conducted in Japan since 1997. Healthy pregnant women aged 20-39 years were recruited and 50 ml of breast milk was collected from them at 30 days after delivery. PCDDs, PCDFs, and dioxin-like PCBs were measured by using GC/MS. The smoking habits of the mothers were established by interviewing them soon after delivery and were classified into four categories: current smokers, ever smokers who quit smoking at the pregnancy, ever smokers who quit smoking before the pregnancy, and never smokers. The levels of dioxins in breast milk were compared in the four categories of smoking among 853 primiparas. In addition, we analyzed the association between dioxin levels and passive smoking among never smokers. The geometric means of the dioxin concentrations were calculated in order to compare the differences between dioxins. RESULTS: The geometric means of dioxin-like PCBs in milk of never smokers was the highest (9.2 pg TEQ/g fat); followed by ever smokers who quit smoking before the pregnancy, ever smokers who quit smoking at the pregnancy, and current smokers (7.5, 7.2, and 6.6 pg TEQ/g fat, respectively). The differences between these levels were statistically significant (ANOVA, p<0.001). No significant difference was observed between the level of dioxins in milk from never smokers subjected to passive smoking status and those who had not experienced passive smoking. CONCLUSION: The levels of dioxin-like PCBs in human milk were negatively related to the smoking habits of mothers. PMID- 17346771 TI - Removal efficiency of a constructed wetland for wastewater treatment according to vegetation dominance. AB - A free water surface wetland was built to treat wastewater containing metals (Cr, Ni and Zn) and nutrients from a tool factory in Santo Tome, Santa Fe, Argentina. Eichhornia crassipes became dominant and covered about 80% of the surface throughout the first year, and decreased progressively until its disappearance. When water depth was lowered Typha domingensis steadily increased plant cover and attained 30% of the surface by the end of the study. While E. crassipes was dominant, the wetland retained 62% of the incoming Cr and 48% of the Ni. NO3- and NO2-, were also removed (65% and 78%, respectively), while dissolved inorganic phosphate (i-P(diss)) and NH4+ were not removed. Zn was below 50 microg l(-1) in both the influent and effluent. Metal concentration in the sediments did not increase and retention was mediated through macrophytes uptake. During the period of E. crassipes decline the wetland retained 49% of the incoming Cr, 45% of Ni, 58% NO3-, 94% NO2-, 58% NH4+ and 47% i-P(diss). Cr, Ni and Zn in the bottom sediment increased in the inlet but not in the outlet. Since T. domingensis became dominant, retention was 58% Cr, 48% Ni and 64% i-P(diss), while 79% NO3-, 84% NO2- and 13% NH4+ were removed. Metals in the bottom sediment increased in the inlet. In spite of the significant growth of E. crassipes at the beginning, T. domingensis remained after most of the transplanted macrophytes had disappeared. Macrophyte disappearance could be related to the overall toxicity of several environmental constrains as high pH and conductivity, metal concentration, and sulphide presence. PMID- 17346772 TI - Solid-state conformations and absolute configurations of (+) and (-) alpha-, beta , and gamma-hexabromocyclododecanes (HBCDs). AB - Hexabromocyclododecanes (HBCDs) are high production volume chemicals used as flame retardants for plastics and textiles. They are currently produced in quantities exceeding 20,000 t/y. Despite this fact, the correct stereochemistry of most HBCDs is still not known. Six stereocenters are formed during bromination of cyclododecatrienes, resulting in mixtures of different stereoisomers. Considering all elements of symmetry, 16 different stereoisomers including six pairs of enantiomers as well as 4 meso forms are possible theoretically. Recently, we isolated 8 of the 16 possible stereoisomers from a technical HBCD mixture and assigned their relative configurations. Herein, we report on the isolation of 6 enantiomerically pure alpha-, beta-, and gamma-HBCDs, obtained from preparative chiral-phase liquid chromatography, and we present their absolute configurations, which were determined from X-ray diffraction analysis. The absolute configuration of (-) alpha-HBCD was found to be (1R,2R,5S,6R,9R,10S), while the one of (+) beta-HBCD is assigned to (1S,2S,5S,6R,9S,10R), whereas the one of (-) gamma-HBCD corresponds to (1S,2S,5S,6R,9R,10S). The given structural information allows the unambiguous identification of the six most important HBCD stereoisomers, which typically account for more than 95% of technical HBCDs. In addition, we compared the solid state conformations of racemic and enantiomerically pure alpha-, beta-, and gamma HBCDs. In all cases, vicinal dibromides adopted a synclinal (sc) conformation with torsion angles of 69+/-6 degrees. A unique structural motive was common to all examined HBCD solid-state conformations. This conserved structure was described as an extended triple turn consisting of an arrangement of three pairs of synclinal and two antiperiplanar torsion angles. PMID- 17346773 TI - Fate of high loads of ammonia in a pond and wetland downstream from a hazardous waste disposal site. AB - Halls Brook (eastern Massachusetts, USA) is a significant source of total dissolved ammonia (sum of NH(3) and NH(4)(+); (NH(3))(T)) to the Aberjona River, a water body listed for NH(3) impairment on the Clean Water Act section 303(d) list. We hypothesized (1) that (NH(3))(T) in Halls Brook derived from a hazardous waste site via groundwater discharging to a two-basin pond that feeds the brook; and (2) that transport of (NH(3))(T) to the Aberjona River was controlled by lacustrine and wetland processes. To test these hypotheses we measured (NH(3))(T) levels in the brook, the pond, and a wetlands directly downstream of the pond during both dry and wet weather over a ten month period. In addition, we analyzed sediment cores and nitrogen isotopes, and performed mass balance calculations. Groundwater discharge from beneath the hazardous waste site was the major source of (NH(3))(T) (20-67 kg d(-1)) and salinity to the north basin of the pond. The salty bottom waters of the north basin were anoxic on all sampling dates, and exhibited relatively stable (NH(3))(T) concentrations between 200 and 600 mg Nl( 1). These levels were >100-times higher than typical background levels, and 8-24 times above the acute effects level for (NH(3))(T) toxicity. Bottom waters from the north basin continuously spill over into the south basin contributing approximately 50% of the (NH(3))(T) load entering this basin. The remainder comes from Halls Brook, which receives (NH(3))(T) loadings from as yet unknown sources upstream. During storm events up to 50% of the mass of (NH(3))(T) was flushed from the south basin and into the wetlands. The wetlands acted as a (NH(3))(T) sink in dry weather in the growing season and a discharge-dependent (NH(3))(T) source to the Aberjona River during rainstorms. PMID- 17346774 TI - Taphonomic analysis of skeletal remains from chimpanzee hunts at Ngogo, Kibale National Park, Uganda. AB - This study provides a taphonomic analysis of the largest known sample of bone fragments collected from chimpanzee hunts. The entire sample consists of 455 bone fragments from 57 chimpanzee hunting episodes of 65 prey individuals at Ngogo, Kibale National Park, Uganda. It has low taxonomic diversity, consisting overwhelmingly of primates, especially red colobus monkeys. The age distribution of the prey remains is skewed towards pre-adults. Cranial bones are the dominant element, followed by long bones. Axial postcranial elements have low survivorship, with a complete absence of pre-caudal vertebrae. Bone is damaged in distinct ways, such as: destruction of long bone ends, typically with intact but chewed shafts; fragmentation and compression cracking of crania; and preservation of only the iliac blades of the innominates. Tooth marks are present but uncommon (4.4% of total NISP). These analyses enable us to: 1) describe and characterize consistent patterns of bone damage inflicted by chimpanzees across a much larger prey sample than has been previously studied; 2) make a preliminary comparison of the generalized chimpanzee taphonomic signature to that of leopard and eagle consumption of primates, as well as modern human consumption of small mammals; and 3) assess the utility of such samples for recognition of early hominin small mammal carnivory. We present a model that may be useful for detecting a pre technological hominin carnivory and suggest some fossil locales at which close inspection of cercopithecoid remains for the above patterns might reveal traces of hominin hunting, though we caution that a pre-technological hominin hunted "assemblage" is not likely to be archaeologically visible. PMID- 17346775 TI - Estimates of associated outdoor particulate matter health risk and costs reductions from alternative building, ventilation and filtration scenarios. AB - Although many studies have reported calculations of outdoor particulate matter (PM) associated externalities using ambient data, there is little information on the role buildings, their ventilation and filtration play. This study provides the framework to evaluate the health risk and cost reduction of building, ventilation and filtration strategies from outdoor PM pollution on a nationwide level and applied it to a case study in Singapore. Combining Indoor Air Quality (IAQ) and time weighted exposure models, with established concentration-response functions and monetary valuation methods, mortality and morbidity effects of outdoor PM on the population of Singapore under different building, ventilation and filtration strategies were estimated. Different interventions were made to compare the effects from the current building conditions. The findings demonstrate that building protection effect reduced approximately half the attributable health cases amounting to US$17.7 billion due to PM pollution when compared to levels computed using outdoor data alone. For residential buildings, nationwide adoption of natural ventilation from current state is associated with 28% higher cases of mortality and 13 to 38% higher cases for different morbidities, amounting to US$6.7 billion. The incurred cost is negligible compared to energy costs of air-conditioning. However, nationwide adoption of closed residence and air-conditioning are associated with outcomes including fewer mortality (10 and 6% respectively), fewer morbidities (8 and 4% respectively) and economic savings of US$1.5 and 0.9 billion respectively. The related savings were about a factor of 9 the energy cost for air-conditioning. Nationwide adoption of mechanical ventilation and filtration from current natural ventilation in schools is associated with fewer asthma hospital admissions and exacerbations; although the economic impact is not substantial. Enhanced workplace filtration reduces the mortality and morbidity cases by 14 and 13% respectively amounting to savings of up to US$2.4 billion. The huge costs savings are comparable to the average worker salary and insignificant to energy, installation and rental cost. Despite uncertainty about accurate benefits, this study shows that health and economic gain via different building, ventilation and filtration designs in minimizing ingress of outdoor PM applied to a nationwide scale can be very large. Importantly, the results suggest that PM associated externalities and legislative efforts should not only focus on ambient PM reduction policies but also include building-informed decisions. PMID- 17346776 TI - Characteristics of emissions of air pollutants from burning of incense in temples, Hong Kong. AB - Field investigations of target air pollutants at two of the most famous temples in Hong Kong were conducted. The air pollution problems in these two temples during peak and non-peak periods were characterized. The target air pollutants included particulate matters (PM(10), PM(2.5)), volatile organic compounds (VOCs), carbonyl compounds, carbon monoxide (CO), nitrogen oxides (NO(x)), methane (CH(4)), non-methane hydrocarbons (NMHC), organic carbon (OC), elemental carbon (EC), and inorganic ions (Cl(-), NO(3)(-), SO(4)(2-), Na(+), NH(4)(+), and K(+)). The pollutant levels of the two temples during peak period were shown to be significantly higher than those during non-peak period. The highest average CO level was obtained at Temple 1 during peak period, which exceeded IAQO 8-h Good Class criteria. In general, the average PM(2.5)/PM(10) ratios were approximately 82%. The results revealed that the fine particulates (PM(2.5)) constituted the majority of suspended particulates at both temples. It was noted that formaldehyde was the most abundant carbonyl compounds, followed by acetaldehyde. At Temple 1 during peak period, the average benzene concentration exceeded almost 8 times more than Indoor Air Quality Objectives for Office Buildings and Public Places (IAQO) [HKEPD, 2003. Guidance notes for the management of indoor air quality in offices and public places. Indoor air quality management group, The Government of the Hong Kong Special Administrative Region.] Good Class criteria. The average OC/EC ratios ranged from 2.6 to 17 in PM(10) and from 4.2 to 18 in PM(2.5) at two temples, which suggested that OC measured in these two temple areas may be due to both direct emission from incense burning and secondary formation by chemical reactions. The total mass of inorganic ions, organic carbon, and elemental carbon accounted for about 71% in PM(2.5) and 72% in PM(10). PMID- 17346777 TI - Interpreting the dioxin and furan profiles in the lichen Ramalina canariensis Steiner for monitoring air pollution. AB - The purpose of this study was to compare the dioxin and furan (PCDD/F) profiles in lichens with those of air and soil. Lichen samples of the species Ramalina canariensis Steiner were collected from 44 different sites and analysed. The results were compared to PCDD/F air and soil profiles from bibliographic data concerning several countries and locations. When compared to other biomonitors (pine needles, vegetation, fruits), lichens were observed to accumulate greater concentrations of PCDD/Fs. The results showed that, although the concentrations of PCDD/Fs in lichens were at the same level of magnitude as those found for soils from the same country (197.5-1218.7 ng kg(-1) and 2.3-15.2 ng I-TEQ kg( 1)), the PCDD/Fs profiles do not reflect soil particle contamination. On the contrary, the PCDD/Fs lichen profiles seemed to be very similar to the ones in the air, at least for the diversity of the ones used for comparison in this study. These results indicated that lichens of the species R. canariensis are potential biomonitors of PCDD/F air pollution. PMID- 17346778 TI - Modelling of the long-term fate of pesticide residues in agricultural soils and their surface exchange with the atmosphere: Part II. Projected long-term fate of pesticide residues. AB - In the first part of this paper, a simple coupled dynamic soil-atmosphere model for studying the gaseous exchange of pesticide soil residues with the atmosphere is described and evaluated by comparing model results with published measurements of pesticide concentrations in air and soil. In Part II, the model is used to study the concentration profiles of pesticide residues in both undisturbed and annually tilled agricultural soils. Future trends are estimated for the measured air and soil concentrations of lindane and six highly persistent pesticides (toxaphene, p,p'-DDE, dieldrin, cis- and trans-chlordane and trans-nonachlor) over a twenty-year period due to volatilization and leaching into the deeper soil. Wet deposition and particle associated pesticide deposition (that increase soil residue concentrations) and soil erosion, degradation in the soil (other than for lindane) and run-off in precipitation are not considered in this study. Estimates of the rain deposition fluxes are reported that show that, other than for lindane, net volatilization fluxes greatly exceed rain deposition fluxes. The model shows that the persistent pesticides studied are highly immobile in soil and that loss of these highly persistent residues from the soil is by volatilization rather than leaching into the deeper soil. The soil residue levels of these six pesticides are currently sources of net volatilization to the atmosphere and will remain so for many years. The maximum rate of volatilization from the soil was simulated by setting the atmospheric background concentration to zero; these simulations show that the rates of volatilization will not be significantly increased since soil resistance rather than the atmospheric concentration controls the volatilization rates. Annual tilling of the soils increases the volatilization loss to the atmosphere. Nonetheless, the model predicts that, if only air-soil exchange is considered, more than 76% of current persistent pesticide residues will remain after 20 years in the top 7 cm of annually tilled soils. In contrast, lindane is relatively mobile in soil due to weaker binding to soil carbon and leaching of lindane into soil is the main removal route for current lindane residues near the soil surface. The model predicts that the soil is a sink for lindane in the atmosphere and that soil residue levels of lindane in the surface soil are determined by a balance between dry gaseous deposition to the soil from the atmosphere and leaching from the surface soil into the deeper soil where degradation is the dominant loss route. The model suggests that deposition of lindane from the atmosphere will sustain residues in the soil and, in the absence of fresh applications of lindane to the soil, eliminating lindane from the atmosphere would lead to a rapid decline of lindane residues in agricultural soils of the southern U.S. PMID- 17346779 TI - Residents' particle exposures in six different communities in Taiwan. AB - Exposure assessment studies for particulates have been conducted in several U.S. and European cities; however, exposure data remain sparse for Asian populations whose cultural practices and living styles are distinct from those in the developed world. This study assessed personal PM(10) exposure in urban residents and evaluated PM(10) indoor/outdoor levels in communities with different characteristics. Important factors of personal PM(10) exposure in Taiwan were explored. Sampling was conducted in 6 communities in Taiwan, two in each of the three major metropolitan areas. Up to nine non-smoking volunteers in each community carried personal samplers for 24 h. The geometric means (GM) of PM(10) in personal, indoor and outdoor samples were 76.3 microg/m(3) (geometric standard deviation, GSD=1.8), 73.4 microg/m(3) (GSD=1.5), and 85.8 microg/m(3) (GSD=1.7), respectively. It was found that outdoor levels rather than indoor levels contributed significantly to personal exposure. The important exposure factors include the time spent outdoors and on transportation, riding a motorcycle, passing by factories, cooking or being in the kitchen, and incense burning at home. Motorcycle riding and the proximity to factories are related to the special living and housing characteristics in Taiwan, while incense burning and Chinese cooking are culture-related. Motorcyclists experienced an average of 27.7 microg/m(3) higher PM(10) than others, while subjects passing by a factory were exposed to an average of 38.4 microg/m(3) higher PM(10) than others. Effective control and public education should be applied to reduce the contribution of these PM exposure sources. PMID- 17346780 TI - Hydrochemical processes controlling arsenic and selenium in the Changjiang River (Yangtze River) system. AB - The hydrochemistry of arsenic and selenium in the Changjiang (Yangtze River) was studied, based on continuously monitored data at Nantong station (i.e. 180 km inland from river mouth), the main Changjiang channel and 10 major tributaries. The dissolved inorganic arsenic (DIAs) and selenium (DISe) concentrations of the Changjiang are related to water discharge, rock type of drain basin, anthropogenic influences etc. The DIAs and DISe levels vary over an order of magnitude throughout the basin (i.e. 6.95-68.9 nmol/L for DIAs, 1.16-9.92 nmol/L for DISe). Source rock composition is the primary control on the concentrations of DIAs and DISe in the Changjiang. Several tributaries (e.g. Xiangjiang River, Minjiang River and Tuojiang River) are contaminated by human activities. Flux calculations from hydrographic data at Datong (the most downstream main channel station without tidal influence) indicate that the Changjiang transports 234.8 x 10(5) mol/yr of DIAs and 49.6 x 10(5) mol/yr of DISe to the East China Sea. PMID- 17346781 TI - Biodegradation of novel amino acid derivatives suitable for complexing agents in pulp bleaching applications. AB - The biodegradability of four novel diethanolamine derivative complexing agents was examined by using two biodegradation tests standardised by OECD (301B and 301F). Ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were employed as reference substances. Biodegradation of the new complexing agents was studied both with unacclimated and acclimated inocula as well as by simulating wastewater treatment in sequencing batch reactors (SBRs). These new complexing agents were of technical grade, and therefore, the results are only indicative but these new compounds hold promise for use as complexing agents in the pulp and paper industry. The novel complexing agents were not readily biodegradable but they showed slight biodegradation. Around 10-30% degradation was found in the SBR where degradation was followed by measurement of concentration. Moreover the novel complexing agents did not have any negative impact on reactor performance as measured by chemical oxygen demand reduction. In the standardised biodegradation tests at best around 50% degradation was observed with the acclimated inoculum and in the prolonged test whereas EDTA and DTPA exhibited no biodegradation. The elevated degradation in acclimated sludge indicates that the water treatment plant microbes are capable of decomposing these molecules under favourable conditions. The total concentration of novel complexing agents decreased slightly during biodegradation tests, while the EDTA and DTPA concentrations remained stable. PMID- 17346782 TI - Destruction of estrogenic activity in water using UV advanced oxidation. AB - The transformation of the steroidal Endocrine Disrupting Compounds (EDCs), 17 beta-estradiol (E2) and 17-alpha-ethinyl estradiol (EE2) by direct UV photolysis and UV/H(2)O(2) advanced oxidation was studied from the perspective of the removal of estrogenic activity associated with the compounds. First, experiments were performed to link the oxidation of E2 and EE2 with subsequent reduction in estrogenic activity. No statistically significant difference between removal rates was observed, implying that the oxidation products of E2 and EE2 are not as estrogenic (measured by the Yeast Estrogen Screen (YES)) as the parent compounds. Utilizing the YES, 90% removal of estrogenic activity of E2 and EE2 at environmentally relevant concentrations ( approximately 3 microg L(-1)) was achieved using a combination of 5 mg L(-1) H(2)O(2) and a UV fluence of less than 350 mJ cm(-2). Thus, these compounds, when considered at environmentally relevant levels, are significantly degraded at much lower UV fluences than previously thought. A steady state OH radical model was used to predict oxidation of EE2 in laboratory and natural waters. PMID- 17346783 TI - Thromboembolic complications in beta-thalassemia: Beyond the horizon. AB - Patients with beta-thalassemia have a chronic hypercoagulable state with increased incidence of thromboembolic episodes. The thrombotic complications are more common in thalassemia intermedia than in regularly transfused thalassemia major. The pathophysiologic defects include inherent red cell defects, platelet abnormalities, deficiency of coagulation inhibitors, and additional acquired abnormalities like cardiac and liver dysfunction, hormonal deficiencies. These factors and possible preventive measures are discussed in this review. An illustrative case is also presented. PMID- 17346784 TI - Early glutamine-enriched enteral feeding facilitates colonic anastomosis healing: light microscopic and immunohistochemical evaluation. AB - Problems related to colonic anastomosis healing constitute the major morbidity in colorectal surgery. Patients without appropriate nutritional support are at higher risk of postsurgical complications, mainly due to reduced wound healing. Therefore, we investigated the effect of early and late postoperative total enteral nutrition (TEN) and glutamine addition on colon anastomosis healing using light microscopy and immunohistochemistry (IGF-I immunolabelling). In this study, 40 Wistar-albino rats underwent distal left colonic transection and anastomosis. The rats were then divided into four groups given different diets: delayed total enteral nutrition (dTEN; beginning 3 days postoperatively), delayed TEN with added glutamine (dTEN+Glutamine), early TEN (eTEN; beginning within 6h postoperatively), and early TEN with added glutamine (eTEN+Glutamine). Colon segments, including the anastomosis, were excised 7 days postoperatively and evaluated histopathologically for inflammation, mucosal healing, submucosal muscular layer repair, the amounts of necrosis and vascularisation and immunohistochemically for IGF-I labelling. The inflammation and necrosis scores in the dTEN and dTEN+Glutamine groups were significantly greater than in the eTEN and eTEN+Glutamine groups. The IGF-I immunoreactivity increased in the eTEN, eTEN+Glutamine, and dTEN+Glutamine groups compared to dTEN (p<0.05). We concluded that early TEN and glutamine enrichment in the postoperative period improve anastomosis healing via IGF-I. PMID- 17346785 TI - Chronic buprenorphine reduces the response to sucrose-associated cues in non food deprived rats. AB - The mechanisms through which buprenorphine (BUP), a mixed opioid agonist antagonist, reduces both heroin and cocaine taking remain unclear. Evidence suggests that chronic exposure to BUP blunts drug seeking by attenuating the salience of drug-associated cues. Here, we examined the effect of chronic BUP treatment (osmotic minipumps, 3.0 mg/kg/day) in rats on responding for sucrose pellets and associated cues on FR1, FR5, and PR schedules and on extinction and reinstatement of sucrose seeking by sucrose priming. The effect of chronic BUP treatment on the dopamine (DA) response in the nucleus accumbens (NAc) to sucrose pellets and to lab chow was also measured using in vivo microdialysis. Whereas chronic BUP treatment had only a modest effect on pellet intake on the FR1 schedule, it significantly reduced responding at the outset of sessions and reduced lever pressing during sucrose-associated cue presentations. No effect was observed in the FR5 or PR schedules. BUP slightly reduced responding during extinction and significantly reduced reinstatement. Chronic BUP did not alter the NAc DA response to either sucrose pellets or lab chow, although it did significantly increase basal DA. Consistent with previous studies with heroin and cocaine, chronic BUP reduced responding in the presence of reward-related cues. PMID- 17346786 TI - Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. AB - Drosophila Piwi-family proteins have been implicated in transposon control. Here, we examine piwi-interacting RNAs (piRNAs) associated with each Drosophila Piwi protein and find that Piwi and Aubergine bind RNAs that are predominantly antisense to transposons, whereas Ago3 complexes contain predominantly sense piRNAs. As in mammals, the majority of Drosophila piRNAs are derived from discrete genomic loci. These loci comprise mainly defective transposon sequences, and some have previously been identified as master regulators of transposon activity. Our data suggest that heterochromatic piRNA loci interact with potentially active, euchromatic transposons to form an adaptive system for transposon control. Complementary relationships between sense and antisense piRNA populations suggest an amplification loop wherein each piRNA-directed cleavage event generates the 5' end of a new piRNA. Thus, sense piRNAs, formed following cleavage of transposon mRNAs may enhance production of antisense piRNAs, complementary to active elements, by directing cleavage of transcripts from master control loci. PMID- 17346787 TI - Adsorption of DNA onto positively charged amidine colloidal spheres and the resultant bridging interaction. AB - The complexation behaviour of duplex linear DNA (negatively charged) with amidine functionalised sub-micron latex spheres (positively charged) was studied using dynamic light scattering (DLS) and a PALS interferrometric zeta potential sizer. Four types of DNA-sphere complex were investigated as a function of component concentration by combining amidine functionalised polystyrene microspheres with radii of 10.5 nm and 60 nm, and herring DNA of lengths of 35 nm and 85 nm. At low DNA concentrations (c(DNA)), the undercharged complexes showed a small increase in measured hydrodynamic radius (R(h)) and a decrease in zeta potential with increasing c(DNA). Within a critical DNA concentration range R(h) was seen to peak sharply, and the zeta potentials were approximately 0 mV, corresponding to the formation of unstable neutral complexes. Immediately above this concentration region the measured R(h) values became comparable with those at low c(DNA), and the zeta potential became negative, indicating the formation of stable overcharged complexes. The small and large spheres formed multi-sphere and single sphere overcharged aggregates respectively, which is thought to be determined by the relative magnitude of the chain persistence length (approximately 50 nm) and the sphere radius, switching on or off the DNA bridging interaction. PMID- 17346788 TI - Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells. AB - We propose a new methodology to enhance the vascular differentiation of human embryonic stem cells (hESCs) by encapsulation in a bioactive hydrogel. hESCs were encapsulated in a dextran-based hydrogel with or without immobilized regulatory factors: a tethered RGD peptide and microencapsulated VEGF(165). The fraction of cells expressing vascular endothelial growth factor (VEGF) receptor KDR/Flk-1, a vascular marker, increased up to 20-fold, as compared to spontaneously differentiated embryoid bodies (EBs). The percentage of encapsulated cells in hydrogels with regulatory factors expressing ectodermal markers including nestin or endodermal markers including alpha-fetoprotein decreased 2- or 3-fold, respectively, as compared to EBs. When the cells were removed from these networks and cultured in media conditions conducive for further vascular differentiation, the number of vascular cells was higher than the number obtained through EBs, using the same media conditions. Functionalized dextran-based hydrogels could thus enable derivation of vascular cells in large quantities, particularly endothelial cells, for potential application in tissue engineering and regenerative medicine. PMID- 17346789 TI - Analysis of progenitor cell-scaffold combinations by in vivo non-invasive photonic imaging. AB - Recent developments in stem cell research have promoted a flourishing of new biomaterials and scaffolds for tissue repair. However, there is a scarcity of procedures to monitor the performance of scaffold-stem cell combinations implanted in live animals, avoiding the inherent artefacts associated with in vitro assay conditions. We report the implementation of a procedure based on the use of the luciferase gene as a cell proliferation tracer to monitor, by in vivo non-invasive imaging, the performance of stem cell-biomaterial combinations used for tissue regeneration. In a model system using immunodepressed mice we show preference of a mouse embryonic mesenchymal cell line (C3H/10T1/2) for specific implantation sites and biomaterials during a prolonged in vivo growth period (3 months). Moreover, we analyzed the safety of implanted cells using a sensitive luminometric procedure and showed that the implanted cells did not spread to other organs. Our results demonstrate the utility of this simple and resource saving procedure in the development and screening of biomaterials for tissue engineering. PMID- 17346790 TI - Hyperglycosylated hCG. AB - Hyperglycosylated hCG (hCG-H) is a glycosylation variant of the hormone hCG. Here we review all that is known about this independently functioning molecule. As discussed, it is a very different molecule to the hormone hCG. First, hCG-H is produced by cytotrophoblast cells while regular hCG is made in syncytiotrophoblast cell. Second, it is an autocrine acting directly on the cells which produce it, while regular hCG is an endocrine acting on maternal corpus luteal cells. Third, hCG-H has minimal biological activity in promoting progesterone production compared to regular hCG. Fourth, hCG-H functions unlike regular hCG as an invasion promoter, whether invasion as in choriocarcinoma and testicular germ cell malignancies, or as in implantation of pregnancy. These functions seemingly occur through action on cytotrophoblast cell TGFbeta receptors. Fifth, hCG-H is an essential component for successful human implantation to prevent early pregnancy loss and spontaneous abortion. Sixth, hCG H is critical for promoting the midtrimester hemochorial implantation, and for preventing preeclampsia. Seventh, measurements of hCG-H have advantages over measurements of regular hCG or total hCG, in detecting pregnancy, pregnancy outcome (failing or term pregnancy), predicting preeclampsia in pregnancy, or as a tumor marker for gestational trophoblastic diseases. PMID- 17346791 TI - Concomitant translocation t(14;22)(q32;q11) in a case of chronic myeloid leukemia. PMID- 17346792 TI - Arsenic accumulation in rice (Oryza sativa L.): human exposure through food chain. AB - Although human exposure to arsenic is thought to be caused mainly through arsenic contaminated underground drinking water, the use of this water for irrigation enhances the possibility of arsenic uptake into crop plants. Rice is the staple food grain in Bangladesh. Arsenic content in straw, grain and husk of rice is especially important since paddy fields are extensively irrigated with underground water having high level of arsenic concentration. However, straw and husk are widely used as cattle feed. Arsenic concentration in rice grain was 0.5+/-0.02 mg kg(-1) with the highest concentrations being in grains grown on soil treated with 40 mg As kg(-1) soil. With the average rice consumption between 400 and 650 g/day by typical adults in the arsenic-affected areas of Bangladesh, the intake of arsenic through rice stood at 0.20-0.35 mg/day. With a daily consumption of 4 L drinking water, arsenic intake through drinking water stands at 0.2mg/day. Moreover, when the rice plant was grown in 60 mg of As kg(-1) soil, arsenic concentrations in rice straw were 20.6+/-0.52 at panicle initiation stage and 23.7+/-0.44 at maturity stage, whereas it was 1.6+/-0.20 mg kg(-1) in husk. Cattle drink a considerable amount of water. So alike human beings, arsenic gets deposited into cattle body through rice straw and husk as well as from drinking water which in turn finds a route into the human body. Arsenic intake in human body from rice and cattle could be potentially important and it exists in addition to that from drinking water. Therefore, a hypothesis has been put forward elucidating the possible food chain pathways through which arsenic may enter into human body. PMID- 17346793 TI - Metal/metalloid contamination and isotopic composition of lead in edible mushrooms and forest soils originating from a smelting area. AB - High metal contents in edible mushrooms growing in severely contaminated industrial areas pose an important toxicological risk. In the presented study, trace element (Pb, Cd, Zn, Cu, Ag, As, Se) contents were determined in caps and stipes of three different edible mushroom species (Boletus edulis Bull. Fr., Xerocomus badius Fr. Gilb., Xerocomus chrysenteron Bull. Quel.). Additionally, information about the chemical fractionation of metals in separate soil horizons and Pb isotopic data from soils and fruiting bodies allowed a more detailed insight on the uptake mechanisms of metals by the studied mushroom species. Total metal and metalloid concentrations in the organic soil horizons reached 36234 mg Pb kg(-1); 11.9 mg Cd kg(-1); 519 mg Zn kg(-1); 488 mg Cu kg(-1); 25.1 mg Ag kg( 1); 120 mg As kg(-1) and 5.88 Se mg kg(-1). In order to evaluate the accumulation capacity of the studied species, bioconcentration factors (BCF) were calculated for separate trace elements. For selected metals (Pb, Cd, Zn, Cu), a modified BCF calculation (using EDTA-extractable concentrations of metals in soil) was proposed. High contents of Pb (up to 165 mg kg(-1)) and Cd (up to 55 mg kg(-1)) exceeded all the regulatory limits in all the studied species. This was also the case for Se (up to 57 mg kg(-1)) in B. edulis. Intensive consumption of this species grown in such polluted areas can therefore pose toxicological risks for human health. A novel finding was that X. badius can act as an Ag accumulating species when grown at polluted sites due to the high concentrations of Ag (up to 190 mg kg(-1)) in caps. Pb isotopic data showed that Pb originating from the recent air pollution control residues is present mainly in the exchangeable/acid extractable fraction of the organic horizons and is taken up by fruiting bodies; especially in the case of B. edulis, where fast Pb accumulation occurs. Due to the high species-dependent variations of metal contents, the studied mushrooms are not suitable as bioindicators of environmental pollution. PMID- 17346794 TI - Gene cloning, sequencing, expression and biological activity of giant panda (Ailuropoda melanoleuca) interferon-alpha. AB - The giant panda (Ailuropoda melanoleuca) is an endangered species and indigenous to China. In mammals, multiple subtypes of interferon-alpha (IFN-alpha) exist, most of which possess antiviral activity. Little is known about giant panda IFN alpha genes and the role they may play in giant panda immunological responses to viruses. We have cloned genes encoding 12 giant panda IFN-alpha (AmIFN-alpha or AmIFNA) subtypes that share from 90 to 99% amino acid sequence identity. AmIFN alpha12 has one additional amino acid at position 57, which is not present in other subtypes. Sequence identity of the AmIFN-alpha proteins encoded by the 12 genes compared to human IFN-alpha2 is approximately 58%. Unlike most of the human subtypes, each of the 12 giant panda IFN sequences has an N-glycosylation recognition site. Expression of all 12 AmIFN-alpha subtypes in 293 cells was confirmed by SDS-PAGE and Western blotting analysis. The antiviral activity and antiproliferative activity of each AmIFN-alpha subtype produced in transiently transfected 293 cell cultures were tested in vitro. All AmIFN-alpha subtypes were found to be stable at pH 2 or 65 degrees C and to exhibit antiviral activity. Some IFN subtypes (AmIFN-alpha8 and AmIFN-alpha4) showed higher biological activity levels than others, whereas AmIFN-alpha11 exhibited lower activity. AmIFN-alpha had various antiproliferative activities to different target cells. To B16 cells, AmIFN-alpha3, AmIFN-alpha4, AmIFN-alpha8 had the highest activities, while to K562 cells, AmIFN-alpha3, AmIFN-alpha7, AmIFN-alpha10 had the highest activities. The various IFN-alpha subtypes displayed a good correlation between their antiviral and antiproliferative potencies. PMID- 17346795 TI - Role of PKCdelta in IFN-gamma-inducible CIITA gene expression. AB - The class II transactivator (CIITA) is a key regulatory factor for MHC class II expression. Here, we demonstrate that PKCdelta plays an important role in regulating IFN-gamma-inducible CIITA gene expression in macrophages. Inhibition of PKCdelta by either a PKCdelta inhibitor or a dominant negative (DN) mutant form of PKCdelta led to down-regulation of CIITA expression. The decrease in CIITA expression by PKCdelta inhibition was in part due to the reduced recruitment of serine 727-phosphorylated Stat1 and histone acetyltransferases to the CIITA promoter. As a result, IFN-gamma induced histone acetylation at the CIITA promoter is also compromised. However, inhibition of PKCdelta did not affect IRF-1 expression or IRF-1 binding to the CIITA promoter. Therefore, we report, for the first time, that PKCdelta is an essential signaling molecule to achieve the maximal expression of CIITA in response to IFN-gamma in macrophages. In addition, although IRF-1 is a key transcription factor to activate the IFN gamma inducible CIITA promoter, the effect of PKCdelta on CIITA expression is mediated primarily by serine phosphorylation of Stat 1. PMID- 17346796 TI - Stable adhesion and migration of human neutrophils requires phospholipase D mediated activation of the integrin CD11b/CD18. AB - The pathways regulating integrin-mediated adhesion during neutrophil migration are incompletely defined. Using a flow-based model in which human neutrophils rolling on P-selectin were activated to migrate by the chemoattractant peptide fMLP, we investigated the role of phospholipase D (PLD). fMLP-stimulated PLD generation of phosphatidate (PtdOH); while inhibition of PtdOH production with butan-1-ol had no effect on the initial immobilisation of rolling neutrophils (supported by activation of constitutively surface-expressed beta(2)-integrin CD11b/CD18) it impaired longer-term stability of adhesion and reduced the rate of migration (supported by activation of de novo-exocytosed CD11b/CD18). PtdOH regulated these processes by controlling activation of exocytosed CD11b/CD18, and appeared to act by directly stimulating phosphatidylinositol 4-phosphate 5-kinase type I to generate phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). Cell permeable PtdIns(4,5)P(2) recovered migration of neutrophils after PLD inhibition; PtdIns(4,5)P(2) appeared to act by promoting talin binding to CD18 and hence activating CD11b/CD18, as migration was inhibited when neutrophils were loaded with peptides previously shown to block the interaction between PtdIns(4,5)P(2) and talin or talin and CD18. Thus, these data indicate that PLD synthesised PtdOH stimulates the generation of PtdIns(4,5)P(2), which in turn mediates talin binding to, and activation of, CD11b/CD18 required for neutrophil stable adhesion and migration. PMID- 17346797 TI - Investigation of the affinity and selectivity of avian prion hexarepeat peptides for physiological divalent metal ions. AB - To further the understanding of the biological importance of metal-binding by avian prion proteins, we have investigated the affinity and selectivity of peptides Hx1 [Ac-HNPGYP-nh] and Hx2 [Ac-NPGYPHNPGYPH-nh] with a range of physiological metals via electrospray ionization mass spectrometry and tyrosine fluorescence emission spectroscopy. Both the hexamer Hx1 and the "dimer" peptide Hx2 bind only one equivalent of Cu(II), although only the latter peptide binds copper with significant affinity (Hx1 K(d)=150+/-35 microM; Hx2 K(d)=1.07+/-0.78 microM, pH 7.0 in 3-(N-morpholino)propanesulfonic acid (MOPS) buffer). Both peptides are selective for Cu(II) over divalent Ca, Co, Mg, Mn, Ni, and Zn. Cyclic voltammetry was used to estimate Cu(II/I) solution potentials at pH 6.8, which were very similar for the two peptides (CuHx1 E degrees'=+350 mV, CuHx2 E degrees'=+320 mV vs. normal hydrogen electrode). These results suggest similar binding modes for the two peptides, and relative stabilization of Cu(I) relative to similar His-Gly-rich peptides in the literature. PMID- 17346798 TI - Sensitively recorded breathing signals of rats and their nonlinear dynamics. AB - Nonlinear dynamical properties of sensitively recorded breathing signals (SRBS), which include cardiac induced air flow pulsations so-called pneumocardiogram (PNCG) signals, are investigated, in this methodological study. For this purpose, we assessed the SRBS of laboratory rat. The nonlinear behaviors of SRBS were investigated by the reconstructing phase space, using the autocorrelation function and the false nearest neighbor method. The chaotic SRBS attractors were discussed from the point of view of the cardiopulmonary system. This method can be used to assess the heart performance and respiratory mechanics, and might be useful to design for the physiological studies of cardiorespiratory system in small laboratory animals. PMID- 17346799 TI - Labeling of dendritic spines with the carbocyanine dye DiI for confocal microscopic imaging in lightly fixed cortical slices. AB - Visualization of dendritic spines is an important tool for researches on structural synaptic plasticity. Fluorescent labeling of the dendrites and spines followed by confocal microscopy permits imaging a large population of dendritic spines with a higher resolution. We sought to establish an optimal protocol to label neurons in cortical slices with the carbocyanine dye DiI for confocal microscopic imaging of dendritic spines. DiI finely labeled dendrites and spines in slices prefixed (by cardiac perfusion) with 1.5% paraformaldehyde to the similar extent that could be achieved in live preparation. In contrast, fixation with 4% paraformaldehyde severely compromised dye diffusion. Confocal microscopy showed that structural integrity of dendrites and spines was preserved much better in lightly (1.5%) fixed slices than those prepared without fixation. Quantitative measurement revealed that spine density was lower in live slices than that counted in lightly fixed slices, suggesting that fixation is necessary for an adequate evaluation of spine density. The quality of confocal microscopic images obtained from lightly fixed slices allowed us to observe distinctive morphologies such as branched spines and dendritic filopodium, which may be indicative of structural changes at synapses. This method will thus be useful for studying structural synaptic plasticity. PMID- 17346800 TI - ADHD-like hyperactivity, with no attention deficit, in adult rats after repeated hypoxia during the equivalent of extreme prematurity. AB - The most common behavioural disorder seen in children and adolescents born extremely prematurely is attention deficit hyperactivity disorder (ADHD). The hyperactive/impulsive sub-type of ADHD or the inattentive sub-type or the hyperactive/impulsive/inattentive sub-type can be evident. These sub-types of ADHD can persist into adulthood. The aim of this study was to investigate the relevance of a new immature rat model of repeated hypoxic exposure to these behavioural characteristics of extreme prematurity. More specifically, this study aimed to measure ADHD-like hyperactivity in response to delayed reward, and inattention, in repeated hypoxic versus repeated normoxic rats. Sprague-Dawley rats were exposed to either repeated hypoxia or repeated normoxia during postnatal days (PN) 1-3. The rat brain during PN1-3 is generally considered to be developmentally equivalent to the human brain during extreme prematurity. The rats were then behaviourally tested at 16 months-of-age on a multiple component fixed interval-extinction test. This test detects ADHD-like hyperactivity in response to delayed reward, as well as inattention. It was found that the repeated hypoxic rats exhibited ADHD-like hyperactivity in response to delayed reward, but no attention deficit, when compared to repeated normoxic rats. These findings provide a new animal model to investigate the biological mechanisms and treatment of ADHD-like hyperactivity due to repeated hypoxia during the equivalent of extreme prematurity. PMID- 17346801 TI - Type-D personality and depressive symptoms predict anxiety 12 months post percutaneous coronary intervention. AB - BACKGROUND: We examined whether type-D personality exerts a stable effect on anxiety over time and the clinical relevance of type-D personality as a predictor of anxiety 12 months post-percutaneous coronary intervention (PCI). METHODS: Consecutive patients (n=416) with stable or unstable angina pectoris treated with PCI completed the Type-D Scale (DS14) at baseline and the Hospital Anxiety and Depression Scale (HADS) at baseline and 12 months. RESULTS: At baseline, 26% of the patients were anxious, with 67% of these patients still being anxious 12 months post-PCI (p<0.001). There was no significant change in anxiety between baseline and 12 months (p=0.96) nor was the interaction effect type-D personality by time significant (p=0.41). However, type-D patients experienced significantly higher levels of anxiety than non-type-D patients (p<0.001). Type-D personality (OR: 2.89; CI: 1.57-5.34), depressive symptoms (OR: 3.27; CI: 1.73-6.18) and anxiety at baseline (OR: 8.38; CI: 4.65-15.12) were independent predictors of anxiety 12 months post-PCI, adjusting for baseline demographic and clinical characteristics. LIMITATIONS: A limitation of the study is the attrition rate of 105 patients who did not complete the HADS at 12 months. No information was available on the use of psychotropic medication and participation in cardiac rehabilitation, which could serve as confounders. CONCLUSION: Type-D exerted a stable effect on anxiety over time and was an independent predictor of anxiety 12 months post-PCI together with depressive symptoms and anxiety at baseline. The DS14 could be used as a screening tool in clinical practice to identify high-risk patients post-PCI. PMID- 17346802 TI - Using ultrasonography to determine thyroid size and prevalence of goiter in lithium-treated patients with affective disorders. AB - BACKGROUND: To determine thyroid gland volume and the prevalence of goiter in patients receiving long-term lithium treatment for affective disorders. METHODS: In this cross-sectional study, we performed ultrasonographic examinations in 96 patients on long-term lithium treatment, including those with bipolar, major depressive, and schizoaffective disease. Patients with documented continuous and adequate serum lithium levels for more than or equal to 6 months were recruited consecutively from the Berlin Lithium Clinic. Ultrasonographic examinations were also performed in 96 gender- and age-matched control subjects. Patients and controls were 18 years of age or older and were residents of Berlin, Germany and surrounding areas. RESULTS: Total thyroid volume was significantly greater in the lithium-treated group than among controls (23.7 ml vs. 13.6 ml). Ultrasonography detected that significantly more lithium-treated subjects had goiter than did control subjects (N=53 vs. N=19). Clinical inspection and palpation only detected goiter in 24 of the lithium-treated patients and in 12 control subjects. In a patient subgroup taking levothyroxine, the prevalence of goiter was still 37%. Patients who were not taking levothyroxine had significantly higher TSH basal levels than normal controls (2.1 mU/L vs. 1.3 mU/L). LIMITATIONS: Cross-sectional study; no control for other factors related to thyroid enlargement and goiter such as dietary issues, smoking, or iodine intake; affectively ill subjects were treated with additional psychotropic medications. CONCLUSIONS: Thyroid enlargement was found in a significant number of lithium-treated patients. Ultrasonography proved superior to palpatory inspection in detecting goiter. Regular use of ultrasonography for early detection of thyroid enlargement in patients on long-term lithium treatment is therefore recommended. PMID- 17346803 TI - Development and application of multiple internal reference (housekeeper) gene assays for accurate normalisation of canine gene expression studies. AB - Measurement of mRNA expression by real-time RT-PCR (QRT-PCR) has proven to be an important and powerful tool for the investigation of the pathogenesis of inflammatory and immune-mediated diseases in many species. This methodology has proven particularly valuable in the dog, a species for which there are currently few specific antibodies for measurement of relevant proteins. Internal control (housekeeper) mRNAs are widely used for normalisation of QRT-PCR results. The validation and use of multiple internal control mRNAs for increased accuracy of normalisation has been described for humans and rodents. The aims of this study were to develop QRT-PCR assays for 11 potential internal control mRNAs in the dog (ACTB, B(2)M, G3PDH, HMBS, HPRT1, RPL13A, RPL32, RPS18, SDHA, TBP and YWAZ) and validate their use with bone marrow, colon, duodenum, heart, kidney, liver, lung, lymph node, skeletal muscle, pancreas, spleen and stomach from seven dogs. Endoscopic biopsies of the superficial duodenal mucosa were also obtained from nine dogs suffering from chronic gastro-oesophageal disease. The most stably expressed genes varied in the tissues examined. RPL13A and RPL32 (both components of the 60S ribosomal subunit) were the most stably expressed genes in the majority of the tissues examined, whereas ACTB and B(2)M were the least stable. Distinct internal control genes were shown to be most appropriate for use in full thickness versus superficial mucosal biopsies of the duodenum. The results of this study indicate that there are no universal control genes for gene expression studies in canine tissues. It is important to use multiple internal control genes based upon a survey of potential control genes applied to representative samples from different disease groups, culture conditions and/or time points in an experimental study. PMID- 17346804 TI - Soluble costimulatory factors sCD28, sCD80, sCD86 and sCD152 in relation to other markers of immune activation in patients with myasthenia gravis. AB - The costimulatory factors CD28, CD80, CD86 and CD152 needed to start and turn off an immune response are present as membrane receptors and soluble proteins. There was no difference in the serum levels of soluble costimulatory molecules in 153 healthy controls and 118 patients with myasthenia gravis. However, we could confirm that the soluble forms of ICAM-1 and CD25 were increased in patients. The concentrations of the soluble costimulatory proteins seemed to be rather constant in individual patients, despite changes in clinical presentation. Thus, the soluble costimulatory factors do not seem to constitute reliable markers for disease activity in myasthenia gravis. PMID- 17346805 TI - A study of associated cell-mediated immune mechanisms in experimental autoimmune neuritis rats. AB - The aims of this study are to investigate the optimal antigens used to induce acute or chronic EAN and the associated cell-mediated immune mechanisms. Lewis rats were grouped into EAN rats and control rats. EAN rats were immunized by injection into both hind footpads of inoculums containing 100 microg/200 microg of P2 peptide 57-81 and FCA, or 200 mug of P0 peptide 180-199 and FCA. Control rats were immunized by FCA. Clinical scores were compared at the maximum of disease. On the 14th day after immunization, we examined lymphocyte proliferation, fractions of CD4+ T cells within lymph node mononuclear cells (MNC), frequencies of CD4+CD25+ T cells within CD4+ T cells, supernatant productions of IFN-gamma, IL-4, IL-10 and TGF-beta1 secreted by lymphocytes. Histopathology of sciatic nerves was assessed. Our findings indicated: (1) 100 microg of P2 peptide 57-81 and 200 microg of P0 peptide 180-199 may induce an acute EAN and 200 microg of P2 peptide 57-81 may induce a chronic EAN; (2) Lewis rats were more sensitive to P2 peptide 57-81 than P0 peptide 180-199; (3) clinical disease had nothing to do with a change of relative CD4+ T cells number in lymph node MNC; (4) frequencies of CD4+CD25+ T cells and levels of TGF-beta1 secreted by lymphocytes negatively paralleled clinical EAN, while levels of IFN gamma secreted by lymphocytes roughly paralleled clinical EAN at the acute phase; (5) sciatic nerve sections from the chronic EAN rats didn't show any inflammatory cells, but showed remaining segmental demyelination and axonal collapse at the chronic phase; (6) self-limitation of acute EAN may owe to the rising levels of IL-4 and IL-10, while a longer duration of chronic EAN may owe to the decreasing levels of IL-4 and IL-10. PMID- 17346806 TI - Temporal bone rhabdomyosarcoma in children. AB - OBJECTIVE: Rhabdomyosarcoma is the most frequent soft tissue sarcoma in the pediatric age group. The authors present their series of rhabdomyosarcoma of the temporal bone in children at Saint Justine Hospital. The twofold objective of this study is to illustrate the clinical presentation, management, and prognosis of this malignant striated muscle tumor, and to compare these results with previously reported series. METHODS: A retrospective study was conducted of patients diagnosed and treated for rhabdomyosarcoma of the head and neck at Saint Justine Hospital, a tertiary pediatric center, between 1970 and 2005. Only cases of temporal bone rhabdomyosarcoma were included in the study. A thorough review of medical and surgical charts was performed to obtain demographic, clinical, paraclinical, and therapeutic data, which were subsequently analyzed and compared to published results. A MEDLINE search yielded 34 studies dealing with temporal bone rhabdomyosarcoma since the year 1966. RESULTS: Thirty-nine patients with rhabdomyosarcoma of the head and neck region were identified, among which only six children had temporal bone rhabdomyosarcoma. The mean age at the time of diagnosis was 4.15 years. Chronic otitis media was the most common clinical presentation. Five children had the embryonal subtype and one had the botryoid subtype on histology. All patients except two received combined chemotherapy and radiotherapy as treatment. Five-year survival rate was 66%. Our results match those reported in the literature 41-81%. CONCLUSION: Rhabdomyosarcoma of the temporal bone is an aggressive tumor that clinically simulates chronic otitis media. A high index of suspicion should be raised in the context of otitis media that is unresponsive to ordinary medical treatment. A biopsy is hence recommended in the presence of polyps in the external auditory canal that are resistant to medical treatment. Early diagnosis and the adoption of multimodal therapy offer the best outcome. PMID- 17346807 TI - The effect of regular versus on-demand desloratadine treatment in children with allergic rhinitis. AB - OBJECTIVE: Desloratadine is a potent antihistamine. Whether regular or on-demand use of desloratadine influences its therapeutic efficacy in allergic rhinitis is unknown. The aim of the study was to compare the clinical efficacy and the anti inflammatory activity of regularly administered desloratadine to its on-demand use in children with allergic rhinitis due to pollen allergy. METHODS: Thirty seven patients with allergic rhinitis with or without mild intermittent asthma were enrolled in a prospective parallel group study. Patients were treated with desloratadine regularly or on-demand during pollen season. Rescue medications and symptom scores were recorded on a diary card. Nasal flow rate and inflammatory markers were recorded, and methacholine (Mch) challenge test was administered before and within the pollen season. RESULTS: Though symptoms were lower in the evening than in the morning (p<0.001), there was no difference between the two groups. There was no difference between the groups with respect to medication score except that the salbutamol use was lower in the regular treatment group during the fourth week (p=0.032) in the pollen season. Nasal flow rate and inflammatory markers failed to show any difference between the groups. A significant reduction in PC20 values (provocative concentration of Mch causing a 20% fall in FEV(1)) was observed in regular (p=0.016) and on-demand (p=0.005) treatment groups compared to the pre-season measurements. The number of children with a PC20 below 8 mg/ml increased significantly in the on-demand group. CONCLUSION: Our study demonstrates that on-demand use of desloratadine during the pollen season is clinically as effective as regular treatment. However, regular treatment may provide better control of lower airway symptoms and airway reactivity. PMID- 17346808 TI - A multiplex nested RT-PCR for the detection and differentiation of wild-type viruses from C-strain vaccine of classical swine fever virus. AB - A multiplex nested RT-PCR (RT-nPCR) was developed for the detection and differentiation of classical swine fever virus (CSFV). A fragment of 447 or 343 bp was amplified from the genomic RNA of C-strain or virulent Shimen strain, respectively, and two fragments of 447 and 343 bp were simultaneously amplified from the mixed samples of C-strain and Shimen. When detecting several wild-type isolates representative of different subgroups (1.1, 2.1, 2.2, and 2.3) circulating in Mainland China and samples from pigs experimentally infected with Shimen strain, the RT-nPCR resulted in an amplification pattern similar to Shimen. No amplification was achieved for uninfected cells, or cells infected with bovine viral diarrhea virus (BVDV), and other viruses of porcine origin. The RT-nPCR was able to detect as little as 0.04 pg of CSFV RNA. The restrictive fragment length polymorphism (RFLP) demonstrated unique patterns of wild-type viruses and C-strain. Among the 133 field samples, 42 were tested to contain wild type viruses and 18 showing presence of C-strain. The RT-nPCR can be used to detect and differentiate pigs infected with wild-type CSFV from those vaccinated with C-strain vaccine, thus minimizing the risk of culling vaccinates during outbreaks. PMID- 17346809 TI - Attempt-dependent decrease in skilled reaching characterizes the acute postsurgical period following a forelimb motor cortex lesion: an experimental demonstration of learned nonuse in the rat. AB - The notion that shock or diaschisis is a distinctive stage in the recovery process following brain damage has played a formative role in the characterization of brain injury. For example, damage to the forelimb region of motor cortex results in an acute period of behavioural depression in skilled reaching and other skilled actions followed by improved performance mediated by compensatory movements. Whereas the progression of improvement and the use of compensatory movements in the chronic period of recovery is well-documented, temporal aspects of behaviour during the acute period of depression of behaviour are relatively unstudied. The present study examined the temporal scheduling of reach-attempts by rats attempting to gain single pellets of food from a shelf in a skilled reaching task. Pretrained rats received contralateral-to-the-pretrained limb forelimb motor cortex lesions. Control lesions included contralateral-to-the pretrained limb parietal cortex lesions, or ipsilateral-to-the-pretrained limb motor cortex lesions. Frame-by-frame video analysis of behaviour showed a decrease in reaching attempts as a function of successive approaches and attempts to grasp the food over the first few postsurgical days in rats with contralateral to-the-pretrained limb motor cortex lesions. A similar approach-dependent decrease in attempts did not occur after parietal or ipsilateral-to-the pretrained limb motor cortex lesions. The decrease in responding occurred only during acute testing and was not observed in rats first tested after 8 days of postoperative recovery. The findings are discussed in relation to the ideas that: (1) the stroke subject is an active participant in modifying behaviour to cope with injury; (2) learned nonuse contributes to behaviour in the acute postinjury period following motor cortex injury; (3) diaschisis inadequately accounts for poststoke behaviour. PMID- 17346810 TI - Immunological responses, histopathological finding and disease resistance of blue mussel (Mytilus edulis) exposed to treated and untreated municipal wastewater. AB - This study provides new information on the response of the immune system of Mytilus edulis exposed to untreated and treated sewage, linking immune response to ecologically relevant endpoints, such as disease resistance. Our goal was to assess the potential effects of sewage on the immune system (phagocytic activity and production of cytotoxic metabolites, disease resistance) and gills (light microscope) of mussels through a bioassay and field study in an estuarine receiving environment (RE). A semi-static experiment was developed in a wastewater treatment plant in New Glasgow, NS Canada. Mussels were exposed for 21 days to 12.5%, 25%, 50% and 100% of untreated sewage influent and artificial seawater control. Sampling occurred after 7, 14 and 21 days of exposure. In the field study, eight sites were selected in East River and Pictou Harbour, NS, positioned upstream and downstream of sewage effluents outfalls. Caged mussels were exposed to the RE for 90 days (May-July 2005). Mussels were challenged to test their efficiency at eliminating the bacteria, Listonella anguillarium in the bioassay and field studies. The bioassay results showed that higher concentrations of untreated sewage could modulate the immune system of mussels through increased of phagocytic activity (PA), nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) production during 14 days of exposure, and decreased activity and production at 21 days, with the exception of H(2)O(2) production which was high even at 21 days. Mussels exposed to untreated sewage RE also presented a high PA, NO and H(2)O(2) production and lower number of haemocytes compared to mussels from reference sites. In the bacterial challenge, mussels pre-exposed to 100% sewage died 24h after being infected with L. anguillarium, while mussels pre exposed to 50% eliminated bacteria had a mortality rate of 30%. Mussels from the control, 12.5% and 25% groups eliminated bacteria and no mortality was observed. No significant difference was observed in bacterial clearance in mussels exposed to effluents in the RE. The lesions observed in gills in both studies were: infiltration of haemocytes in the tissue, epithelium proliferation, lamellar fusion and dilated haemolymphatic sinus. In summary, untreated municipal wastewater affected the immune system of blue mussels during 21 days of exposure and the effects were reflected in their capability to resist pathogens. And an immune modulation was observed in mussels exposed to untreated sewage in a RE, but this modulation was not reflected in the mussel's capability in eliminating pathogens. PMID- 17346811 TI - BVT.3531 reduces body weight and activates K(ATP) channels in isolated arcuate neurons in rats. AB - A number of hormones, including leptin, have been shown to inhibit food intake in humans and animals. Analogues of 3-guanidinopropionic acid have also been found to reduce total food intake, but their mechanisms of action have not been well studied. The present study investigated the effects of intracerebroventricular infusion of the analogue BVT.3531 on food intake, meal pattern, and body weight in rats during 7 days. Single channel recordings from arcuate neurons and insulinoma cells were used to determine the effects of BVT.3531 on K(ATP) activity. Data analysis showed that BVT.3531 significantly decreased body weight and food intake, primarily by reducing meal size. BVT.3531 activated K(ATP) channels in cell-attached recordings from insulin-secreting cells and rat arcuate neurons but had no effect on K(ATP) channel activity in inside-out membrane patches from either cell type. BVT.3531 did not alter the firing rate or K(+) channel activity of arcuate neurons devoid of K(ATP). The study suggests that small molecules capable of mimicking the effects of leptin on food intake and body weight may utilize output mechanisms similar to those of leptin to elicit changes in arcuate neuron excitability. PMID- 17346812 TI - Mediators of glucagon-like peptide 2-induced blood flow: responses in different vascular sites. AB - The aims of the present study were: to characterize the mechanisms of hemodynamic alterations induced by GLP-2, and, to compare the responses elicited in the superior mesenteric artery (SMA) to other vascular beds. Anesthetized rats were infused at the doses of 0.9, 2.3, 4.6 and 9.3 nmol/kg into the jugular vein for 60 min. Blood flow in the various arteries was measured by the ultrasonic transit time technique. Some animals were pretreated with indomethacin (5 mg/kg, ip), L NAME (9, 18, 36 and 72 micromol/kg, iv), atropine sulfate (1-2 mg/kg, iv), CCK-1 and CCK-2 receptor antagonists (L-364,718 and L-365,260, 1 mg/kg, iv), exendin (9 39) amide (35 nmol/kg, iv) and lidocaine (74 micromol/kg, iv) prior to the infusion of GLP-2 (4.6 nmol/kg). In another group, capsaicin was applied either systematically (125 mg/kg, sc) or vagally (1 mg/rat). GLP-2 administration at all doses significantly increased the SMA blood flow throughout the experiments. GLP 2 (4.6 nmol/kg) infusion significantly increased blood flow of inferior mesenteric artery and carotid artery but not in any other vessel measured. Only the pretreatments with L-NAME and lidocaine were ineffective in preventing the GLP-2-induced responses. These results implicate that GLP-2-induced blood flow alterations are most significant in the SMA and are not mediated by prostaglandins, muscarinic, GLP-1 or CCK receptors. Our results also suggest that the stimulatory effect of GLP-2 on SMA blood flow is NO-dependent and mediated via intrinsic, non-cholinergic enteric neurons. PMID- 17346813 TI - Expression of PACAP and glutamate transporter proteins in satellite oligodendrocytes of the human CNS. AB - White matter oligodendrocytes have been shown to actively regulate extracellular glutamate levels in the CNS. Such function has yet not been examined in satellite oligodendrocytes of gray matter. Similar to those in white matter, satellite oligodendrocytes are involved in myelination. In addition, they modulate the activity of surrounding neurons. This study examined whether satellite oligodendrocytes express PACAP and glutamate transporter proteins and whether this expression is influenced by global ischemia. We demonstrated expression of PACAP27 and PACAP38 in a major fraction of satellite oligodendrocytes in normal neocortex and hippocampus of human brain tissues obtained post-mortem. All three glutamate transporters EAAT1, EAAT2 and EAAT3 were expressed in satellite oligodendrocytes from these tissues. Thus, satellite oligodendrocytes may participate in the perineuronal glutamate homeostasis. Following transient global ischemia, the total number of satellite oligodendrocytes expressing PACAP or glutamate transporter proteins was significantly decreased in cerebral neocortex and hippocampus. However, alterations of PACAP and glutamate transporter protein expression were region and time specific. In satellite oligodendrocytes of CA1 an early strong reduction of PACAP and glutamate transporter expression was observed. This contrasted with late reduction of PACAP27, PACAP38 and glutamate transporters EAAT1, EAAT2 and EAAT3 in satellite oligodendrocytes of neocortex. Further studies should clarify whether these alterations in protein expression are primary or secondary to neuronal cell death. PMID- 17346814 TI - Molecular cloning of two isoforms of Xenopus (Silurana) tropicalis estrogen receptor mRNA and their expression during development. AB - Native estrogens and estrogenic chemicals exert their actions primarily through the nuclear estrogen receptors (ERs). The present study is directed towards providing a molecular basis for detection of estrogenic and antiestrogenic effects of compounds. In the present study, we isolated successfully two isoforms of a full-length ER mRNA from the liver of Xenopus (Silurana) tropicalis, and analyzed their expression in various tissues during the development by RT-PCR method. The isolated full-length ERalpha and ERbeta cDNAs contained a 1755-bp and a 1644-bp coding regions, respectively. The deduced amino acid sequence of X. tropicalis ERalpha was highly homologous to previously published X. tropicalis ERalpha, Xenopus laevis ERs (xer3, ERalpha1, and ERalpha2), and X. laevis ER related proteins. The N-terminal region of the X. tropicalis ERalpha amino acid sequence cloned in the present study was more highly homologous to that of the xer3 amino acid sequence than the previously published X. tropicalis ERalpha sequence. Some amino acid residues in the D domain were absent in this sequence. In contrast, the deduced amino acid sequence of the C and E/F domains in X. tropicalis ERbeta was highly homologous to those in teleosts, quail, and human ERbetas. The RT-PCR analysis showed that expression of the two ER transcripts was relatively abundant in the brain, liver, and gonad/kidney complex of 2-month-old froglet, but weakly expressed in the heart, stomach, leg muscle, and back skin. Gonadal sex differentiation occurred histologically in the X. tropicalis tadpole between Nieuwkoop and Faber stages 54 and 59. The ERalpha transcripts in the brain, liver and gonad/kidney complex, and ERbeta in the brain were expressed at low levels in the tadpole at stage 51, but became extremely abundant in the tadpole at stage 60, and remained at relatively high levels in the froglet after metamorphosis. In contrast, ERbeta transcript was expressed abundantly in a consistent manner in the liver and gonad/kidney complex from stage 51 through metamorphosis. Expression of the two ER transcripts was recognized at almost the same levels in both sexes during the development, except for relatively lower expression of ERbeta in the female gonad after metamorphosis. These results taken together suggest that the brain, liver, and gonad/kidney complex of the X. tropicalis tadpole may be more susceptible to toxic influences by exogenous estrogenic substances after sex differentiation. PMID- 17346815 TI - 5-HT1A receptor-mediated apoptosis: death by JNK? AB - There is growing interest in the potential use of 5-HT(1A) receptor agonists as neuroprotective agents in stroke and traumatic brain injury. However, a new study using a recombinant 5-HT(1A) receptor cell line suggests that these agonists may promote as well as inhibit apoptotic responses. Because heterologously expressed receptors may couple promiscuously to inappropriate signal transduction pathways, the results should be interpreted with caution. PMID- 17346816 TI - Nicorandil suppressed myocardial injury after percutaneous coronary intervention. AB - BACKGROUND: Nicorandil exerts beneficial effects as an adjunctive therapy for patients with ischemic heart disease. This study was designed to assess the effects of nicorandil on the myocardial protective benefits of elective percutaneous coronary intervention (PCI). METHODS: We randomly divided 49 patients scheduled to undergo elective PCI into two groups, nicorandil and control. Before PCI, the former received an intravenous bolus injection of nicorandil (4 mg), followed by continuous infusion at 6 mg/h for 24 h after intervention. Oral administration of nicorandil was continued until follow-up coronary angiography (CAG). Serial venous blood samples, for measurement of creatine kinase (CK), creatine kinase MB isoform (CK-MB), troponin I (TnI) and myoglobin, were obtained before PCI, and at 0 h, 4 h, 24 h and 48 h after PCI. Left ventricular function and left ventricular wall motion were evaluated by means of contrast ventriculography before PCI and follow-up CAG. RESULTS: At 24 h after PCI, elevations of cardiac enzymes were significantly suppressed in the nicorandil as compared to the control group; CK (78.1+/-34.9 versus 117.4+/-137.9 U/l, P=0.0141), CK-MB (1.57+/-1.90 versus 2.67+/-4.50 U/l, P=0.0485) and TnI (0.37+/-0.55 versus 0.86+/-1.65 ng/ml, P=0.0101). Regional left ventricular wall motion was significantly improved at follow-up in the nicorandil as compared to the control group. CONCLUSIONS: Nicorandil suppressed elevations of cardiac enzymes after elective PCI and left ventricular wall motion was also significantly improved at follow-up, suggesting that nicorandil enhances the myocardial protective effect of PCI against angioplasty-related myocardial injury. PMID- 17346817 TI - Blood B-type natriuretic peptide level increases in patients who complain shortness of breath and chest pain in the course of panic attack. AB - OBJECTIVE: Blood pro-B-type natriuretic peptide (pro-BNP) level increases in case of myocardial ischemia and myocardial volume or pressure overload. The aim of this study is to measure changes in blood pro-BNP level during the course of panic attack with symptoms of chest pain and/or dyspnea. METHODS: Patients who were admitted to the emergency room with panic attack have been regarded as the study group. Blood pro-BNP level has been measured during follow-up of the patients upon admission and 2h later. RESULTS: Systolic and diastolic blood pressure and pulse rate were significantly decreased (p<0.0001) during follow-up of the patients (ages between 18 and 43 years; mean 26+/-6.13 years). Paradoxically, blood pro-BNP level of patients was significantly increased during the same period (52.86+/-59.73 versus 50.97+/-57.42 U/L; p<0.0001). CONCLUSION: Blood pro-BNP level has increased among patients who have complained chest pain and/or dyspnea as symptoms of panic attack. It is thought that chest pain and dyspnea in the course of panic attack may not be purely psychological. PMID- 17346818 TI - How good are experienced interventional cardiologists at predicting the functional significance of intermediate or equivocal left main coronary artery stenoses? AB - BACKGROUND: Decisions for coronary revascularisation are frequently based on visual assessment of the severity of a stenosis. In patients with intermediate left main stem lesions clinical decision making based on FFR is safe and feasible. This study was performed to assess the accuracy of visual angiographic assessment of intermediate or equivocal left main coronary artery (LMCA) stenoses by experienced interventional cardiologists when taking fractional flow reserve (FFR) measurements as the gold standard. METHODS: Fifty-one patients with intermediate (40-80% diameter stenosis by angiography) or equivocal LMCA disease were evaluated by FFR. Angiograms were then reviewed by 4 experienced interventionalists from different university hospitals blinded to FFR results. Lesions were visually assessed and their significance classified as 'significant', 'not significant', or 'unsure' if the observer was unable to make a decision regarding lesion significance based on the angiogram. RESULTS: Results were compared with two different FFR cutoff values (< 0.75 and < or = 0.80) for hemodynamic significance. The 4 reviewers achieved correct lesion classification in no more than approximately 50% of cases each, regardless of FFR threshold. The interobserver agreement between two reviewers in excess of the agreement expected due to chance was outperformed on average by only 16%. Furthermore, interobserver variability was large resulting in unanimously correct lesion classification in only 29% of all cases. CONCLUSIONS: The functional significance of intermediate and equivocal LMCA stenoses should not be based solely on angiographic assessment even by experienced interventional cardiologists. PMID- 17346819 TI - Aortic stiffness is increased in acromegaly--a transthoracic echocardiographic study. AB - BACKGROUND: Acromegaly is associated with increased cardiovascular risk. Recent studies suggested a direct effect of growth hormone and insuline-like growth factor 1 excess on the vasculature over the conventional risk factors. The aim of the present study was to evaluate the stiffness of ascending aorta by means of transthoracic echocardiography (TTE) in patients with acromegaly. PATIENTS AND METHODS: The following patient populations were compared: 20 subjects with negative coronary angiograms, 16 acromegalics and 21 patients with significant coronary artery disease (CAD). Aortic stiffness index (beta) was evaluated by means of TTE by use of the formula: beta=ln (SBP/DBP)/(DeltaD/DD), where SBP and DBP are the systolic and diastolic blood pressures, DD is the diastolic aortic diameter, DeltaD is the pulsatile change in aortic diameter (systolic diameter minus diastolic diameter) and 'ln' is the natural logarithm. RESULTS: The average time from diagnosis was 162+/-127 days in acromegalic patients. Transsphenoidal hypophysectomy was performed in 12 patients, while the mean growth hormone level was 10.8+/-11.7 mIU/ml. beta was similarly increased in acromegalics and in CAD patients as compared to controls (6.23+/-3.29 vs 16.47+/-14.53 and 16.66+/-15.49, p<0.05, respectively). CONCLUSIONS: Stiffness of ascending aorta evaluated by a routine TTE examination is increased in acromegalics without overt cardiovascular disease as compared to controls and similar to CAD patients. PMID- 17346820 TI - Thiamine deficiency as a rare cause of reversible severe pulmonary hypertension. AB - In developed countries, the incidence of cardiac beriberi is rare. It can lead to high output cardiac failure and pulmonary hypertension. We hereby report an atypical case of beriberi heart with reversible right heart failure and severe pulmonary hypertension. Thiamine deficiency can cause reversible pulmonary hypertension, and it must be included in the differential diagnosis in patients with high risk of nutritional deficiency. PMID- 17346821 TI - Stent-related cardiac events after non-cardiac surgery: drug-eluting stent vs. bare metal stent. AB - For evaluation of post-operative stent associated cardiac events after drug eluting stent (DES) implantation we analyzed data of 138 patients who underwent non-cardiac surgery after DES implantation and compared the data with those of 101 patients who underwent non-cardiac surgery after bare metal stent (BMS) implantation. Three patients (2.2%) in DES group developed post-operative cardiac events and none in BMS group (p=0.2). One patient died due to suspected stent thrombosis and the other two had myocardial infarction due to angiographically proven stent thrombosis. The time interval between stent implantation and surgery in those with cardiac events was 6, 264, and 367 days, respectively. Our data shows that peri-operative stent-related thrombotic complications can occur long after DES implantation and careful peri-operative monitoring for cardiac events is needed in patients receiving non-cardiac surgery after DES implantation. PMID- 17346822 TI - Response to letter of Dr van Werkum et al. PMID- 17346823 TI - An anomalous left main coronary artery with coronary torsion originating from the right sinus Valsalva. AB - A 52-year old woman developed inferior ST elevation myocardial infarction and was found to have both an anomalous left coronary artery originating from the right sinus of Valsalva, and total atherosclerotic occlusion of the proximal right coronary artery. Coronary angiography showed the torsion of left main coronary artery. Multislice computed tomography was used to assess the left main coronary artery. PMID- 17346824 TI - Cardiac rupture and tamponade during ventriculography. AB - Left ventricular free wall rupture after a myocardial infarction is a complication which is unusually seen during ventriculography. We present the case of a patient who developed a cardiac rupture and tamponade captured on ventriculography. PMID- 17346825 TI - Vasopressin dysregulation: hyponatremia, fluid retention and congestive heart failure. AB - Arginine vasopressin (AVP) plays a central role in the regulation of water and electrolyte balance. Dysregulation of AVP secretion, along with stimulation of AVP V2 receptors, is responsible for hyponatremia (serum sodium concentration <135 mEq/L) in congestive heart failure (CHF). The stimulation of atrial and arterial baroreceptors in response to hypotension and volume depletion results in the nonosmotic release of AVP. The predominance of nonosmotic AVP secretion over osmotic AVP release plays a key role in the development of water imbalance and hyponatremia in CHF and other edematous disorders. The AVP-receptor antagonists are a new class of agents that block the effects of AVP directly at V2 receptors in the renal collecting ducts. AVP-receptor antagonism produces aquaresis, the electrolyte-sparing excretion of water, thereby allowing specific correction of water and sodium imbalance. This review summarizes recent data from clinical trials evaluating the efficacy and safety of these promising agents for the treatment of hyponatremia. PMID- 17346826 TI - Pneumopericardium after blunt chest trauma: mechanical ventilation with positive pressure must be avoided. AB - A 38-year-old polytraumatized man was admitted with signs of cardiogenic shock (low blood pressure, tachycardia, tachypnea, and elevated central venous pressure). A near tension pneumopericardium was revealed by thorax CT. Air from the pericardial sac remissed 4 days later conservatively, avoiding invasive or non-invasive mechanical ventilation. The use of positive-pressure ventilation, with or without intubation, would probably lead to tension pneumopericardium cardiac tamponade, needing emergent decompression. PMID- 17346827 TI - Nocturia in males with heart failure: prostatic edema and circadian neurohormonal rhythm. PMID- 17346828 TI - A double acute coronary syndrome and early left ventricular thrombus formation associated to C-reactive protein elevation at admission. PMID- 17346829 TI - No evidence for involvement of prothrombotic platelet receptor polymorphisms in acute coronary stent thrombosis. AB - Polymorphisms of receptors involved in platelet adhesion and aggregation modulate platelet thrombogenicity and were found to predispose to premature arterial thromboses in individuals at risk. In our current study, we assessed the potential relevance of prothrombotic platelet receptor polymorphisms for the pathogenesis of acute coronary stent thrombosis. Comparing the genotype prevalences of respective polymorphisms in patients with acute coronary stent thrombosis and healthy control subjects, our data do not indicate an increased risk of carriers of prothrombotic variants of platelet receptors for this complication. Other factors such as the remodelling process and antiplatelet medication appear to be more relevant in this clinical setting. Along with our findings, screening for respective polymorphisms for risk assessment prior to coronary stenting is not indicated. PMID- 17346830 TI - Risk factors for Campylobacter spp. colonization in French free-range broiler chicken flocks at the end of the indoor rearing period. AB - The aim of this cross-sectional survey was to identify risk factors for Campylobacter spp. colonization in French free-range broiler flocks at the end of the indoor rearing period (between 35 and 42 days old). Seventy-three broiler farms were studied from March 2003 to March 2004 in France. A questionnaire was administered to the farmers and samples of fresh droppings were taken to assess the flocks'Campylobacter status by bacteriology. Campylobacter species were determined by PCR. A logistic regression analysis was used to assess the influence of various factors on flocks'Campylobacter status. 71.2% of the sampled flocks excreted Campylobacter spp. before going out on the range. The risk of a flock being colonized with Campylobacter was increased in the spring/summer period (RR=1.8, p=0.02) and autumn (RR=2.2, p=0.02) compared to winter, on total freedom rearing farms (RR=3.3, p=0.04) in comparison with farms with a fenced run, when the first disinfection of the poultry-house was performed by the farmer (RR=2.4, p=0.04) instead of a hygiene specialist, when rodent control was carried out by a contractor (RR=1.8, p<0.01) and not by the farmer and when the farmer came into the house twice a day as opposed to three time a day or more (RR=1.5, p=0.02). Use of a specific gate for chick placement decreased the risk of a flock being colonized with Campylobacter (RR=0.5, p=0.01) in comparison with using the gate for manual disposure or the door of the change room. PMID- 17346831 TI - REMA: A computer-based mapping tool for analysis of restriction sites in multiple DNA sequences. AB - REMA is an interactive web-based program which predicts endonuclease cut sites in DNA sequences. It analyses multiple sequences simultaneously and predicts the number and size of fragments as well as provides restriction maps. The users can select single or paired combinations of all commercially available enzymes. Additionally, REMA permits prediction of multiple sequence terminal fragment sizes and suggests suitable restriction enzymes for maximally discriminatory results. REMA is an easy to use, web based program which will have a wide application in molecular biology research. AVAILABILITY: REMA is written in Perl and is freely available for non-commercial use. Detailed information on installation can be obtained from Jan Szubert (jan.szubert@gmail.com) and the web based application is accessible on the internet at the URL http://www.macaulay.ac.uk/rema CONTACT: b.singh@macaulay.ac.uk. PMID- 17346832 TI - An extended ToxR POSSYCCAT system for positive and negative selection of self interacting transmembrane domains. AB - Assay systems based on the ToxR protein are widely used to investigate interaction of transmembrane domains that come from natural proteins or are isolated from combinatorial libraries. The principle of this method is that self interaction of any given transmembrane domain, which is expressed within a ToxR chimeric protein, drives ToxR-ToxR assembly in a bacterial inner membrane. In current versions of the system, ToxR-ToxR interaction drives transcription activation of the cholera toxin (ctx) promoter and thereby induces expression of downstream reporter genes in appropriately constructed bacterial strains. Here, we describe the application of other known ToxR-regulated promoters. We show that interacting transmembrane domains also promote ToxR-driven activation of the ompU promoter. Conversely, these interactions efficiently repress transcription from the constitutively active ompT promoter. We present novel Escherichia coli strains whose chromosomes harbor fusions of ompU or ompT promoters with different reporter genes. Depending on the used promoter, self-interaction of transmembrane domains induces or represses reporter enzyme expression in these cells. These strains extend current applications of the ToxR protein and may find use in mapping transmembrane helix-helix interfaces and selection of transmembrane domains with medium affinities. PMID- 17346833 TI - Pasteurella multocida detection by 5' Taq nuclease assay: a new tool for use in diagnosing fowl cholera. AB - A 5' Taq nuclease assay utilising minor groove binder technology and targeting the 16S rRNA gene was designed to detect Pasteurella multocida (the causative agent of fowl cholera) in swabs collected from poultry. The assay was first evaluated using pure cultures. The assay correctly identified four P. multocida taxonomic type strains, 18 P. multocida serovar reference strains and 40 Australian field isolates (17 from poultry, 11 from pigs and 12 from cattle). Representatives of nine other Pasteurella species, 26 other bacterial species (18 being members of the family Pasteurellaceae) and four poultry virus isolates did not react in the assay. The assay detected a minimum of approximately 10 cfu of P. multocida per reaction. Of 79 poultry swabs submitted to the laboratory for routine bacteriological culture, 17 were positive in the 5' Taq nuclease assay, but only 10 were positive by culture. The other 62 swabs were negative for P. multocida by both 5' Taq nuclease assay and culture. The assay is suitable for use in diagnosing fowl cholera, is more rapid than bacteriological culture, and may also have application in diagnosing P. multocida infections in cattle and pigs. PMID- 17346834 TI - Comparison of multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and amplified fragment length polymorphism (AFLP) for genetic typing of Staphylococcus aureus. AB - We compared multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and amplified fragment length polymorphism (AFLP) for typing of Staphylococcus aureus and show that the methods yield similar results, although with differences in resolving power and reproducibility. Epidemiological conditions should determine which is the optimal typing method to be used. PMID- 17346835 TI - Assessment of Southern blot ribotyping for differentiation of Leptospira strains isolated from field rats. AB - A Southern blot ribotyping based on EcoRV and HindIII digestion with two 16S and 23S rDNA probes for differentiating 27 Leptospira serovars was developed. The results between ribotyping and serotyping among 40 leptospiral strains isolated from field rats trapped in the northeastern region of Thailand during 1999-2000, were compared. A combination of Southern blot ribotyping, using EcoRV or HindIII digestion with both 16S and 23S rDNA as the probes, successfully typed 27 Leptospira serovars into 24 ribotypes with the discriminatory index (D) values of 0.99. The 16S- and 23S-EcoRV ribopatterns produced 17 and 9 profiles, respectively, with D values of 0.95 and 0.63, respectively. Ribopatterns of HindIII from both specific probes yielded 17 patterns. The D values of 16S- and 23S-HindIII ribopatterns were 0.94 and 0.93, respectively. With EcoRV digestion, the 16S rDNA probe was more discriminative than the 23S rDNA probe for differentiating Leptospira serovars. Moreover, the 16S-EcoRV (11 profiles), 16S HindIII (11 profiles), and 23S-HindIII (10 profiles) ribopatterns produced higher numbers of distinct and unique profiles than the 23S-EcoRV (5 profiles). The results showed 100% concordance between ribotyping and serotyping, leading to all 40 isolates being successfully typed. The current study revealed that ribotyping as a quick and powerful tool for differentiating Leptospira serovars, has potential value in epidemiological studies. PMID- 17346836 TI - A combined approach for the enhanced detection and isolation of Bartonella species in dog blood samples: pre-enrichment liquid culture followed by PCR and subculture onto agar plates. AB - Historically, direct plating, lysis centrifugation, or freeze-thaw approaches have proven to be highly insensitive methods for confirming Bartonella species infection in dogs. A prospective study was designed to compare diagnostic methods for the detection of Bartonella using samples submitted to the Vector-Borne Disease Diagnostic Laboratory at North Carolina State University. Methods included indirect immunofluorescence assay, PCR, direct inoculation of a blood agar plate (trypticase soy agar with 5% rabbit blood), and inoculation into a novel pre-enrichment liquid medium, Bartonella/alpha-Proteobacteria growth medium (BAPGM). Sequential research efforts resulted in the development of a combinational approach consisting of pre-enrichment culture of Bartonella species in BAPGM, sub-inoculation of the liquid culture onto agar plates, followed by DNA amplification using PCR. The multi-faceted approach resulted in substantial improvement in the microbiological detection and isolation of Bartonella when compared to direct inoculation of a blood agar plate. Importantly, this approach facilitated the detection and subsequent isolation of both single and co infections with two Bartonella species in the blood of naturally infected dogs. The use of a combinational approach of pre-enrichment culture and PCR may assist in the diagnostic confirmation of bartonellosis in dogs and other animals. PMID- 17346837 TI - Time, action, and consciousness. AB - Time plays a central role in consciousness, at different levels and in different aspects of information processing. Subliminal perception experiments demonstrate that stimuli presented too briefly to enter conscious awareness are nevertheless processed to some extent. Implicit learning, implicit memory, and conditioning studies suggest that the extent to which memory traces are available for verbal report and for cognitive control is likewise dependent on the time available for processing during acquisition. Differences in the time available for processing also determine not only the extent to which one becomes conscious of action, but also provides the basis for making attributions of authorship to experienced acts. In this paper, we offer a brief overview of these different findings and suggest that they can all be understood based on the fact that consciousness takes time. From this perspective, the availability of representations to conscious awareness depends on the quality of these representations - the extent to which they are strong, stable in time, and distinctive. High-quality representations occur when processes of global competition have had sufficient time to operate so as to make the system settle into the best possible interpretation of the input. Such processes implement global constraint satisfaction and critically depend on reentrant processing, through which representations can be further enriched by high-level constraints. We discuss these ideas in light of current theories of consciousness, emphasizing the fact that consciousness should be viewed as a process rather than as a static property associated with some states and not with others. PMID- 17346838 TI - Anticipatory response control in motor sequence learning: evidence from stimulus response compatibility. AB - Three experiments using a serial four-choice reaction-time (RT) task explored the interaction of sequence learning and stimulus-based response conflict. In Experiment 1, the spatial stimulus-response (S-R) mapping was manipulated between participants. Incompatible S-R mappings produced much higher RTs than the compatible mapping, but sequence learning decreased this S-R compatibility effect. In Experiment 2, the spatial stimulus feature was made task-irrelevant by assigning responses to symbols that were presented at unpredictable locations. The data indicated a Simon effect (i.e., increased RT when irrelevant stimulus location is spatially incompatible with response location) that was reduced by sequence learning. However, this effect was observed only in participants who developed an explicit sequence representation. Experiment 3 replicated this learning-based modulation of the Simon effect using explicit sequence-learning instructions. Taken together, the data support the notion that explicit sequence learning can lead to motor 'chunking', so that pre-planned response sequences are shielded from conflicting stimulus information. PMID- 17346839 TI - FK506 reduces the severity of cutaneous hypersensitivity in rats with a spinal cord contusion. AB - Spinal cord injury (SCI) leads to persistent pain as well as motor dysfunction, both of which lack effective therapeutics. The immunosuppressant FK506 (tacrolimus) has been shown to improve behavioral outcome following SCI in rats. Just prior to a mid-thoracic spinal cord contusion injury, rats were injected with either vehicle or FK506 and treatment was continued through the duration of the experiment. Vehicle-treated rats developed significant and long-lasting hind paw hypersensitivity to innocuous mechanical stimulation, noxious heat and cooling stimuli. In contrast, FK506 treatment reduced the duration of both mechanical and cold hypersensitivity. Neither treated groups demonstrated an improvement in locomotor function. Thus, some SCI-induced pain is mediated by an FK506-sensitive mechanism. The data also suggest that motor and sensory dysfunctions resulting from SCI are mediated by distinct mechanisms, requiring the use of multiple therapeutic interventions. PMID- 17346840 TI - Enological characterization of natural hybrids from Saccharomyces cerevisiae and S. kudriavzevii. AB - The effect of yeasts on wine flavor response is of primary importance. The genus Saccharomyces, and mainly the species Saccharomyces cerevisiae, is responsible for alcoholic fermentation. Recently, several novel yeast isolates from wines have been described as hybrid yeasts between S. cerevisiae x S. kudriavzevii. We have analyzed their influence on two grape musts (Macabeo and Tempranillo) in fermentations conducted at four different temperatures (14, 18, 22 and 32 degrees C) by studying volatile compound production, sugar assimilation and other characteristics influencing the enological properties of wine caused by the impact of yeast. Hybrid yeasts behave particularly well at 14, 18 and 22 degrees C and the commercial strain of S. cerevisiae (T73) is better adapted at higher temperatures. Regarding the production of glycerol, acetic acid and malic acid, the hybrids display moderate behavior and concerning aromatic compound production, they are greater producers of higher alcohols. The behavior displayed by these hybrids in the fermentations studied in this work leads us to conclude that the use of hybrid strains can constitute an advantage in wine making. PMID- 17346841 TI - Enhanced production of secretory beta1,3-N-acetylglucosaminyltransferase 2 fusion protein into hemolymph of Bombyx mori larvae using recombinant BmNPV bacmid integrated signal sequence. AB - The enhanced secretion of beta1,3-N-acetylglucosaminyltransferase 2 (beta3GnT2) fusion protein into the hemolymph of Bombyx mori larvae was studied using a recombinant B. mori nucleopolyhedrovirus (BmNPV) bacmid integrating seven signal sequences. When the BmNPV bacmid encoding the signal sequences from the silkworm B. mori bombyxin (bx) and B. mori prophenoloxidase-activating enzyme (ppae) was injected into silkworm larvae, 56.1 and 51.5mU/ml beta3GnT, respectively, were secreted into the hemolymph of silkworm larvae. For bx, 97.3% of the total beta3GnT activity was secreted into hemolymph, and only 1.1% remained in the intestines of silkworm larvae. For ppae, 90.8% of the total beta3GnT activity was secreted to the hemolymph, but 7.8% remained in the intestines of silkworm larvae. Using the BmNPV bacmid encoding bx, the amount of secreted beta3GnT was 91mug per larva, which was 2.5% of the total amount of protein in the hemolymph. PMID- 17346842 TI - Yeast-based screening to identify modulators of G-protein signaling using uncontrolled cell division cycle by overexpression of Stm1. AB - Stm1, a G-protein coupled receptor, which senses nutritional state drives cells to stop the proliferative cell cycle and enter meiosis under nutritionally deficient conditions in Schizosaccharomyces pombe. It was shown that overexpression of Stm1 led growth inhibition and uncontrolled mitotic haploidization presumably by the premature initiation of mitosis. Sty1 and Gpa2 seem to play important roles for Stm1 to deliver starvation signal to induce downstream function. Based on the observation that conversion of diploid to haploid by overexpression of Stm1 can be easily detected as pink or red colonies in the media containing low adenine, HTS drug screening system to identify modulators of GPCR was established and tested using 413 compounds. Four very potent modulators of GPCR including Biochanin A, which possess strong inhibitory activity against uncontrolled cell division, were identified in this screening. This study provides the yeast-based platform that allows robust cellular assays to identify novel modulators of G-protein signaling and MAP kinase pathway. PMID- 17346843 TI - Development of a fed-batch process for the production of the cytochrome P450 monooxygenase CYP102A1 from Bacillus megaterium in E. coli. AB - A fed-batch process utilizing a pET-based expression system (pET28a+ derivative) and E. coli BL21(DE3) as production strain for the heterologous expression of recombinant cytochrome P450 monooxygenase CYP102A1 from Bacillus megaterium was developed. In a first step the expression was optimized during a series of flask experiments testing several parameters for their influence on the expression level, activity and solubility of the recombinant protein. The optimal process parameters found in the flask experiments were transferred to a cultivation process in a 5l (operating volume) bioreactor with a special focus on the feeding strategy and the aeration during expression. Glycerol feeding proved to be superior over glucose as carbon source since the formation of larger amounts of acetate was prevented. Expression levels exceeding 12,500nmoll(-1), corresponding to approximately 1.5gl(-1) of product in culture medium ( approximately 11% of CDW) could be demonstrated. The P450 enzyme showed high activity and high solubility. The findings now can be transferred to other enzyme variants and different P450 monooxygenases to increase production of recombinant proteins. PMID- 17346844 TI - Remnant cationic dendrimers block RNA migration in electrophoresis after monophasic lysis. AB - Cationic dendrimers such as poly(amidoamine) (PAMAM) and poly(propyleneimine) (PPI) have attractive characteristics for the delivery of nucleic acid and various biomedical applications. Most studies have focused on cationic dendrimer based intracellular delivery, and very few studies have focused on the non specific interaction of remnant cationic dendrimers with total RNA after isolation directly from cells in vitro. We examined RNA isolation using the common method of monophasic lysis from human macrophage-like cells (U937) and mouse fibroblast cells (NIH/3T3) that had been exposed to dendrimers and DNA/dendrimer complexes using gel electrophoresis. We found that PAMAM and PPI dendrimers strongly altered the mobility of RNA in the gels. In addition, the extent of dendrimer-induced alteration in RNA mobility was directly dendrimer generation-dependent: the alteration was greater with higher-generation dendrimers. We also found that DNA/dendrimer complexes at higher dendrimer to DNA ratios interacted with RNA after isolation while gene expression was maintained. The interactions between RNA and remnant dendrimers after isolation were caused by electrostatic bindings, and we recovered total RNA using high ionic strength solvents (2M NaCl solution) to disrupt the electrostatic forces binding dendrimers to RNA. Because RNA isolation is routinely used for biological applications, such dendrimer-induced alteration in RNA mobility should be accounted for in the further processing of RNA-related applications. PMID- 17346845 TI - Poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) nanoparticles for local delivery of paclitaxel for restenosis treatment. AB - Catheter-based local delivery of biodegradable nanoparticles (NP) with sustained release characteristics represents a therapeutic approach to reduce restenosis. Paclitaxel-loaded NP consisting of poly(vinyl alcohol)-graft-poly(lactide-co glycolide) (PVA-g-PLGA) with varying PLGA chain length as well as poly(lactide-co glycolide) (PLGA), were prepared by a solvent evaporation technique. NP of <180 nm in diameter characterized by photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) are spherical and show smooth surfaces. Yields typically range from 80 to 95% with encapsulation efficiencies between 77 and 87%. The extent of initial in vitro paclitaxel release was affected by the PVA-g-PLGA composition. Blank nanoparticles from PVA(300)-g-PLGA(30) and PVA(300)-g-PLGA(15) showed excellent biocompatibility in rabbit vascular smooth muscle cells (RbVSMC) at polymer concentrations of 0.37 mg/ml. Paclitaxel-loaded NP have an increased antiproliferative effect on cells in comparison to free drug. Confocal laser scanning microscopy of RbVSMC confirmed cellular uptake of nanoparticles composed of fluorescently labeled PVA(300)-g-PLGA(15) loaded with Oregon Green labeled paclitaxel. Cells showed a clearly increased fluorescence activity with a co-localization of paclitaxel and polymer nanoparticles during incubation with particle suspension. To evaluate the antirestenotic effect in vivo, paclitaxel-loaded nanoparticles were administered locally to the wall of balloon-injured rabbit iliac arteries using a porous balloon catheter. As a result a 50% reduction in neointimal area in vessel segments treated with paclitaxel-loaded nanoparticles compared to control vessel segments could be observed (local paclitaxel nanoparticle treated segments 0.80+/ 0.19 mm(2), control segments 1.58+/-0.6 mm(2); p<0.05). PMID- 17346846 TI - The combination of fasting plasma glucose and glycosylated hemoglobin predicts type 2 diabetes in Japanese workers. AB - OBJECTIVES: We examined the usefulness of the combined use of fasting plasma glucose (FPG) and hemoglobin Alc (HbA1c) levels to predict the progression of diabetes in a Japanese population. METHODS: A retrospective cohort study was conducted from 1995 to 2002 among 449 non-diabetic Japanese workers, ages 23-65, in whom baseline FPG levels and HbA1c were measured. Subjects were classified into six groups according to their baseline FPG level: low normal fasting glucose (NFG) (<5.55 mmol/l); high NFG (5.55-6.09 mmol/l); or impaired fasting glucose (IFG) (6.10-6.99 mmol/l), in combination with baseline HbA1c level: low HbA1c (<5.8%) and high HbA1c (> or =5.8%). The cumulative incidence of diabetes in 2002, as defined by the 1997 American Diabetes Association (ADA) diagnostic criteria, was compared between groups. RESULTS: The overall cumulative incidence of diabetes was 3.8% (17/449). The cumulative incidence of diabetes was 0.6% (2/339) in those with low NFG/normal HbA1c; 0% (0/24) with low NFG/high HbA1c; 6.4% (3/47) with high NFG/normal HbA1c; 23.1% (3/13) with high NFG/high HbA1c; 17.6% (3/17) with IFG/normal HbA1c; and 66.7% (9/17) with IFG/high HbA1c. The odds ratios for diabetes, adjusted for age, sex, body mass index (BMI) and family history of diabetes, were 5.3 (95% CI, 3.0-9.3) and 3.0 (1.7-5.3), per 0.56 mmol/l increase in FPG and 0.5% increase in HbA1c, respectively. CONCLUSIONS: The combined use of FPG and HbA1c levels predicts the progression to diabetes in individuals with no apparent risk. In particular, the combination is recommended for individuals with a FPG > or =5.55 mmol/l. PMID- 17346847 TI - Patient attitudes towards chemotherapy as assessed by patient versus physician: a prospective observational study in advanced non-small cell lung cancer. AB - BACKGROUND: In the treatment of advanced cancer, a physician's ability to accurately identify a patient's attitude towards treatment is critical. This paper describes the extent of any differences observed between patient attitudes towards chemotherapy for advanced non-small cell lung cancer (NSCLC) as assessed by patients themselves versus their physicians. PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC who received gemcitabine plus cisplatin or carboplatin were enrolled into this prospective observational study. Patients and their physicians completed questionnaires containing descriptions of seven patient-specific attitudes. A pre-defined algorithm was used to categorize patients into one of the three 'need' categories based on the questionnaire responses: (A) "maximum extension of survival with acceptance of high toxicity", (B) "maximum extension of survival only if coupled with normal life style", and (C) "relief of symptoms". Each patient was categorized based on his own response, as well as his physician's response. RESULTS: A total of 1895 patients were enrolled from 19 countries across 3 continents. Data from 1884 patients were analysed. Based on patient versus physician responses, respectively, the distribution of patients was 60% versus 39% in need category A, 26% versus 33% in B, and 14% versus 29% in C. Patient self-assessed versus physician-assessed need category identification was aligned for 891 patients (47.3%): 541 (29%) in A, 218 (12%) in B, 132 (7%) in C. While there was slight agreement between the identification of 'need' categories by physicians and patients (kappa=0.18, 95% CI: 0.15-0.21), physicians also tended to place patients further down the scale (towards C) than patients placed themselves (P<0.001). CONCLUSIONS: Patients have varying needs from cancer chemotherapy and it may not always be correctly identified by the treating physician. Physicians may underestimate patient's desire for extended survival compared with symptom relief. PMID- 17346848 TI - Effects of exotic species on evolutionary diversification. AB - Exotic species invasions create almost ideal conditions for promoting evolutionary diversification: establishment of allopatric populations in new environmental conditions; altered ecological opportunities for native species; and new opportunities for hybridization between previously allopatric taxa. Here, we review recent studies of the evolutionary consequences of species invasions, revealing abundant and widespread examples of exotic species promoting evolutionary diversification via increased genetic differentiation among populations of both exotic and native species and the creation of new hybrid lineages. Our review indicates that, although the well-documented reductions to biodiversity caused by exotic species might outweigh the increases resulting from diversification, a complete understanding of the net effects of exotic species on biodiversity in the long term will require consideration of both. PMID- 17346849 TI - Direct simulation of heterogeneous diffusion and inversion procedure applied to an out-diffusion experiment. Test case of Palmottu granite. AB - An out-diffusion laboratory experiment using a non-reactive tracer was fitted using the Time Domain Diffusion (TDD) method. This rapid particle tracking method allows simulation of the heterogeneous diffusion based on pore-scale images and local values of diffusivities. The superimposed porosity and mineral 2D maps act as computation grids to condition diffusion pathways. We focused on a Palmottu granite sample, in which the connected pore space has a composite microstructure with cracks linking microporous minerals and is above the percolation threshold. Three main results were achieved: (i) When compared to the fitting obtained with one coefficient (best mean square residual R = 1.6 x 10(-2)), diffusion is shown to be suitably characterised with two coefficients related to cracks and microporous minerals (best R = 6.5 x 10(-4)), (ii) rather than imposing a local apparent diffusion coefficient D(a) independent of the local porosity Phi, a best fit is obtained by applying Archie's relationship D(a) = D(0) x G with G = Phi(m) to each pixel of the calculation grids (G is the geometry factor, D(0) is the diffusion coefficient in free fluid, and m is Archie's exponent), and (iii) the order of magnitude of the fitted diffusion coefficient or Archie's exponents (m=0 for microcracks and m=1.82 for microporous minerals) is physically realistic. PMID- 17346850 TI - Estimating the hydraulic properties of the fracture network in a sandstone aquifer. AB - The potential hydraulic behaviour of the fracture network in a major Triassic sandstone aquifer in the UK has been evaluated. The properties of the fracture network were determined using results from detailed scan line surveys at 10 sites, television and geophysical borehole logging, and packer testing. Six sets of discontinuities common to all sites were identified and statistically characterised (dip, strike, orientation, density, size, and estimated transmissivity). A discrete fracture network model was then used stochastically to investigate the properties of the network. In general, the network is poorly connected: it is estimated that 9% of the discontinuities intersecting boreholes are transmissive. The hydraulic behaviour of the network is generally dominated by one sub-horizontal bedding plane fracture set, although when present, a relatively infrequent north-south striking, sub-vertical set modifies the bulk flow properties significantly. Ignoring this latter set, the network's minimum representative volume is about 35 x 35 x 35 m. The upscaled permeability is anisotropic, being typically 23 times greater in the horizontal than in the vertical. Tortuosity in the north-south direction is around 1.6. PMID- 17346851 TI - Inhibitory effects of glucocorticoids on urocortin-mediated increases in interleukin-6 gene expression in rat aortic smooth muscle cells. AB - Urocortin (Ucn) 1, Ucn2, and Ucn3 have potent effects on appetite and the cardiovascular system. Endogenous Ucns in combination with CRF receptor type 2beta may have a physiological role in the cardiovascular system. We previously demonstrated that both Ucn1 and Ucn2 increased IL-6 output levels in A7r5 aortic smooth muscle cells. In the present study, we extended observations on stress or hormone-induced changes in IL-6 gene expression in the cardiovascular system, and determined the effects of glucocorticoids on Ucn-mediated increases in IL-6 mRNA levels, protein levels, and gene transcription activity in A7r5 cells. Ucn1, Ucn2, and Ucn3 all increased IL-6 mRNA levels via CRF receptor type 2. Dexamethasone blocked the ability of Ucn1 to increase IL-6 mRNA and protein levels, while it failed to attenuate the Ucns-mediated changes in cyclic AMP (cAMP)-response element binding protein or extracellular signal-related kinases phosphorylation. Dexamethasone also suppressed Ucn1- or cAMP-stimulated IL-6 gene transcription via a glucocorticoid receptor. Together, these findings demonstrate that glucocorticoids suppress IL-6 gene transcription via Ucn-induced cAMP dependent pathways in A7r5 cells. PMID- 17346852 TI - Central leptin gene therapy corrects skeletal abnormalities in leptin-deficient ob/ob mice. AB - Skeletal growth is tightly coupled to energy balance via complex and incompletely understood mechanisms. Leptin-deficient ob/ob mice are obese and develop multiple pathologies associated with the metabolic syndrome. Additionally, ob/ob mice have skeletal abnormalities. The objective of this study was to evaluate the effects of leptin deficiency and long duration selective central leptin repletion via recombinant adeno-associated virus-leptin (rAAV-lep) gene therapy on bone in growing ob/ob mice. The ob/ob mice were injected in the hypothalamus with either rAAV-lep or rAAV-GFP (control vector). Treated ob/ob and untreated wild-type (WT) mice were then maintained on a normal diet for 15 weeks. In a second experiment, similarly treated mice along with a group of pair-fed mice were maintained for 30 weeks. Leptin was not detected in blood of either rAAV-lep- or rAAV-GFP-treated mice although rAAV-lep-treated mice displayed leptin transgene expression in the hypothalamus. As expected, rAAV-lep normalized body weight and food intake. Compared to WT mice, rAAV-GFP-treated ob/ob mice had decreased femoral length (by 1.6 mm or 10%, P<0.001), decreased total femur bone volume (by 3.3 mm(3) or 19%, P<0.001), but increased cancellous bone volume in the distal femur (by 0.04 mm(3) or 60%, P<0.09) and lumbar vertebrae (by 0.26 mm(3) or 118%, P<0.001). Treatment with rAAV-lep rescued the ob/ob skeletal phenotype by increasing femoral length and total bone volume, and decreasing femoral and vertebral cancellous bone volume, so that at 15 weeks post-rAAV-lep injection the ob/ob mice no longer differed from WT mice. No further skeletal changes in either the femur or lumbar vertebra were observed at 30 weeks post-rAAV-lep administration. The results suggest that hypothalamic leptin functions as an essential permissive factor for normal bone growth. PMID- 17346853 TI - Expression of adrenomedullin2/intermedin in human brain, heart, and kidney. AB - Adrenomedullin2/intermedin (AM2/IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CGRP) family. In the present study, we developed a specific radioimmunoassay of human AM2/IMD. Expression of AM2/IMD was studied in the human brain, pituitary, heart and kidney obtained at autopsy by radioimmunoassay and immunocytochemistry. Immunoreactive-AM2/IMD was detected by radioimmunoassay in human brains (range; 0.163-1.495 pmol/g wet weight), pituitaries (4.46+/-0.689 pmol/g wet weight, mean+/-S.E.M, n=3), left ventricles of hearts (0.251+/-0.0321 pmol/g wet weight, n=4), kidneys (3.49+/-1.18 pmol/g wet weight, n=5), and plasma obtained at healthy subjects (24.7+/-1.78 pmol/l, n=3). Reverse-phase high performance liquid chromatography showed that immunoreactive-AM2/IMD in human brain, kidney and plasma extracts were eluted in the position of authentic AM2/IMD. Additional peaks eluted earlier were found in the brain tissue and plasma. Immunocytochemistry showed that immunoreactive AM2/IMD was localized in paraventricular and supraoptic nuclei of hypothalamus, anterior and posterior lobes of pituitary, cardiomyocytes, pericardial adipocytes, vascular endothelial cells of pericardial veins, and vascular smooth muscle cells of coronary arteries and renal arterioles as well as in renal tubular cells. The present study has shown expression of AM2/IMD in various types of cells in the central nervous system and the cardiovascular system, and suggested possible (patho)physiological roles of AM2/IMD in these systems. PMID- 17346854 TI - The metabolic role of isoleucine in detoxification of ammonia in cultured mouse neurons and astrocytes. AB - Cerebral hyperammonemia is a hallmark of hepatic encephalopathy, a debilitating condition arising secondary to liver disease. Pyruvate oxidation including tricarboxylic acid (TCA) cycle metabolism has been suggested to be inhibited by hyperammonemia at the pyruvate and alpha-ketoglutarate dehydrogenase steps. Catabolism of the branched-chain amino acid isoleucine provides both acetyl-CoA and succinyl-CoA, thus by-passing both the pyruvate dehydrogenase and the alpha ketoglutarate dehydrogenase steps. Potentially, this will enable the TCA cycle to work in the face of ammonium-induced inhibition. In addition, this will provide the alpha-ketoglutarate carbon skeleton for glutamate and glutamine synthesis by glutamate dehydrogenase and glutamine synthetase (astrocytes only), respectively, both reactions fixing ammonium. Cultured cerebellar neurons (primarily glutamatergic) or astrocytes were incubated in the presence of either [U 13C]glucose (2.5 mM) and isoleucine (1 mM) or [U-13C]isoleucine and glucose. Cell cultures were treated with an acute ammonium chloride load of 2 (astrocytes) or 5 mM (neurons and astrocytes) and incorporation of 13C-label into glutamate, aspartate, glutamine and alanine was determined employing mass spectrometry. Labeling from [U-13C]glucose in glutamate and aspartate increased as a result of ammonium-treatment in both neurons and astrocytes, suggesting that the TCA cycle was not inhibited. Labeling in alanine increased in neurons but not in astrocytes, indicating elevated glycolysis in neurons. For both neurons and astrocytes, labeling from [U-13C]isoleucine entered glutamate and aspartate albeit to a lower extent than from [U-13C]glucose. Labeling in glutamate and aspartate from [U-13C]isoleucine was decreased by ammonium treatment in neurons but not in astrocytes, the former probably reflecting increased metabolism of unlabeled glucose. In astrocytes, ammonia treatment resulted in glutamine production and release to the medium, partially supported by catabolism of [U 13C]isoleucine. In conclusion, i) neuronal and astrocytic TCA cycle metabolism was not inhibited by ammonium and ii) isoleucine may provide the carbon skeleton for synthesis of glutamate/glutamine in the detoxification of ammonium. PMID- 17346855 TI - Feature processing during visual search in normal aging: electrophysiological evidence. AB - Event-related potentials (ERPs) were recorded from healthy young and older subjects during the execution of a visual search task in which they were required to detect the presence of a target stimulus that differed from distractors in a salient feature (orientation). Apart from the orientation target, a task irrelevant singleton defined by a different feature (color) was also presented without instruction. The effects of normal aging on the N2pc component, an electrophysiological correlate of the allocation of visuospatial attention, were evaluated for the first time. Behavioral results showed an increase in the mean reaction time (RT) and a reduction in the hit rates with age. Electrophysiological results showed a consistent N2pc for orientation target pop outs but not for irrelevant color pop-outs in both age groups, suggesting that the irrelevant color singleton did not induce attentional capture. Furthermore, the N2pc component observed for orientation targets was significantly delayed and attenuated in older subjects compared to young subjects, suggesting a specific impairment of the allocation of visuospatial attention with advancing age. PMID- 17346856 TI - Reversion of age-related recognition memory impairment by iron chelation in rats. AB - It is now generally accepted that iron accumulates in the brain during the ageing process. Increasing evidence demonstrate that iron accumulation in selective regions of the brain may generate free radicals, thereby possessing implications for the etiology of neurodegenerative disorders. In a previous study we have reported that aged rats present recognition memory deficits. The aim of the present study was to evaluate the effect of desferoxamine (DFO), an iron chelator agent, on age-induced memory impairment. Aged Wistar rats received intraperitoneal injections of saline or DFO (300mg/kg) for 2 weeks. The animals were submitted to a novel object recognition task 24h after the last injection. DFO-treated rats showed normal recognition memory while the saline group showed long-term recognition memory deficits. The results show that DFO is able to reverse age-induced recognition memory deficits. We also demonstrated that DFO reduced the oxidative damage to proteins in cortex and hippocampus. Thus, the present findings provide the first evidence that iron chelators might prevent age related memory dysfunction. PMID- 17346858 TI - Synthesis and pharmacological evaluation of novel conformationally constrained homologues of glutamic acid. AB - Twelve novel conformationally constrained homologues of glutamic acid have been synthesized and pharmacologically characterized at ionotropic glutamate receptors (iGluRs). Synthesis of the target compounds involved 1,3-dipolar cycloaddition of nitrile oxides to suitable dipolarophiles. The structure to the compounds has been assigned by (1)H NMR and, in the case of derivatives (+/-)-4a, (+/-)-4b, (+/ )-5a, and (+/-)-5b, by means of an X-ray crystallographic analysis carried out on intermediate (+/-)-12a. The synthesized amino acids were found to be without affinity (K(i)/IC(50)>100microM) for iGluRs with the exception of compounds (+/-) 4b and (+/-)-5b, which showed a modest affinity for NMDA receptors (K(i)=34 and 13microM, respectively). The results indicate that the increased conformational constraints introduced by the cyclopropane ring and the spiro-attached proline ring are both detrimental to the pharmacological activity. PMID- 17346857 TI - Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. AB - Inhaled anesthetics have been shown to increase the aggregation of amyloid beta in vitro through the stabilization of intermediate toxic oligomers, which are thought to contribute to neurocognitive dysfunction in Alzheimer's disease. Inhaled anesthetics may escalate cognitive dysfunction through enhancement of these intermediate oligomer concentrations. We intermittently exposed 12-month old Tg2576 transgenic mice and nontransgenic littermates to isoflurane and halothane for 5 days. Cognitive function was measured before and after anesthetic exposures using the Morris Water Maze; amyloid beta plaque burden and caspase-3 mediated apoptosis were quantified by immunohistochemistry. At 12 months of age, anesthetic exposure did not further enhance cognitive decline in the transgenic mice. Immunohistochemistry, however, revealed that the halothane-exposed Tg2576 mice had more amyloidopathy than the isoflurane treated mice or the nonexposed transgenic mice. Isoflurane exposure impaired cognitive function in the nontransgenic mice, implying an alternative pathway for neurodegeneration. These findings indicate that inhaled anesthetics influence cognition and amyloidogenesis, but that the mechanistic relationship remains unclear. PMID- 17346859 TI - Design, synthesis and melatoninergic activity of new unsubstituted and beta,beta' difunctionalised 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-6-alkanamides. AB - A series of new 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-6-alkanamides, with and without alkyl and cycloalkyl moieties in the beta-position of the alkanamido side chain, have been prepared and tested for their ability to activate pigment granule aggregation in Xenopus laevis melanophores and bind to the recombinant human MT(1) and MT(2) melatonin receptor subtypes expressed in NIH 3T3 cells. An increase of the spacer's length in the side chain by a methylene unit (from 17d to 21d) leads to a six-fold decrease in antagonistic activity. On the other hand, the introduction of two methyl groups in the beta-position of the side chain of 17a induces agonist potency (compound 24), implying thus that the two beta-methyl groups are not only tolerated by the receptor, but constitute functional probes in its dynamic agonist-antagonist conformational equilibrium. The presence of more bulky beta-substituents, regardless of the size of the R group, compounds 24a,b, seems to lead to antagonism and to a noteworthy MT(2) subtype selectivity. Last, the new N1-C7 annulated derivatives presented herein are substantially more potent than their respective N1-C2 annulated counterparts, previously reported. PMID- 17346860 TI - Convenient one pot synthesis and antimicrobial evaluation of some new Mannich bases carrying 4-methylthiobenzyl moiety. AB - Two new series of Mannich bases, namely, 1-(morpholino)methyl-3-(4 methylthiobenzyl)-4-(substituted arylidene)amino-1,2,4-triazol-5-thiones 3 and 1 (N-methylpiperazino)methyl-3-(4-methylthiobenzyl)-4-(substituted arylidene)amino 1,2,4-triazol-5-thiones 4 have been synthesized by a three-component Mannich reaction (MCR) involving 3-(4-methylthiobenzyl)-4-(substituted arylidene)amino-5 mercapto-1,2,4-triazoles 2, formaldehyde and morpholine/N-methylpiperazine. The newly synthesized compounds were well characterized by elemental analysis, IR, (1)H NMR and mass spectral studies. They were also screened for their antibacterial and antifungal activities against a variety of microorganisms and the results of such studies have been discussed in this article. PMID- 17346861 TI - The consequences of scoring docked ligand conformations using free energy correlations. AB - Ligands from a set of 19 protein-ligand complexes were re-docked with AutoDock, GOLD and FlexX using the scoring algorithms native to these programs supplemented by analysis using the HINT free energy force field. A HINT scoring function was calibrated for this data set using a simple linear regression of total HINT score for crystal-structure complexes vs. measured free energy of binding. This function had an r(2) of 0.84 and a standard error of +/-0.42 kcal mol(-1). The free energies of binding were calculated for the best poses using the AutoDock, GOLD and FlexX scoring functions. The AutoDock and GoldScore algorithms estimated more than half of the binding free energies within the reported calibration standard errors for these functions, while that of FlexX did not. In contrast, the calibrated HINT scoring function identified optimized poses with standard errors near +/-0.5 kcal mol(-1). When the metric of success is minimum RMSD (vs. crystallographic coordinates) the three docking programs were more successful, with mean RMSDs for the top-ranking poses in the 19 complexes of 3.38, 2.52 and 2.62 A for AutoDock, GOLD and FlexX, respectively. Two key observations in this study have general relevance for computational medicinal chemistry: first, while optimizing RMSD with docking score functions is clearly of value, these functions may be less well optimized for free energy of binding, which has broader applicability in virtual screening and drug discovery than RMSD; second, scoring functions uniquely calibrated for the data set or sets under study should nearly always be preferable to universal scoring functions. Due to these advantages, the poses selected by the HINT score also required less post-docking structure optimization to produce usable molecular models. Most of these features may be achievable with other scoring functions. PMID- 17346862 TI - Synthesis of 6- and 9-alkylaminomethyl furoflavones as gastroprotective agents. AB - The synthesis of 9- and 6-alkylaminomethyl furoflavones 5a, b, 9a-c, 13a, b, 15a g and 18 from the naturally occurring chromones visnagin and khellin. Gastroprotective potency of these compounds in the ethanol damage model was determined. The results indicate that, through appropriate substitution, furoflavones can be obtained that are gastroprotective. PMID- 17346863 TI - Oral immunization of mice with the live vaccine strain (LVS) of Francisella tularensis protects mice against respiratory challenge with virulent type A F. tularensis. AB - Francisella tularensis is a Gram-negative intracellular bacterium, and the causative agent of tularemia. The infection can be initiated by various routes and can manifest itself in several clinical forms with the disseminated typhoidal form initiated by inhalation being most fatal. The attenuated live vaccine strain (LVS), developed almost 50 years ago, remains the sole effective tularemia vaccine, which is still only available as an investigational new drug for at-risk individuals. This vaccine, when given by scarification, appears to provide solid protection against subsequent systemic infection with clinical strains of F. tularensis, but its efficacy against respiratory infection is less satisfactory. In this study, we evaluated the potential of oral immunization with LVS for eliciting protection against systemic and respiratory infection with virulent F. tularensis strains in a mouse model of tularemia. Oral LVS immunization was highly effective at protecting Balb/c mice against lethal systemic or respiratory challenges with type A and type B F. tularensis. Compared to sham-immunized mice, oral LVS-immunized mice showed significant reductions in burdens of virulent F. tularensis in the lung and spleen and milder tissue damage and inflammation in the liver. The immunization induced F. tularensis-specific antibody responses in the serum and bronchoalveolar lavage fluids, as well as antigen-specific splenocyte proliferation and IFN-gamma and IL-2 production. The protective efficacy was related to the size of the immunizing dose but not the number of doses administered. Like other routes of LVS immunization in mice, the protective immunity induced by oral immunization was relatively short-lived. These results suggest that oral immunization should be explored further as an alternative vaccination strategy to combat tularemia. PMID- 17346864 TI - An unusual punch injury. PMID- 17346865 TI - The role of the subscapularis in preventing anterior glenohumeral subluxation in the abducted, externally rotated position of the arm. AB - BACKGROUND: Current literature suggests that the subscapularis muscle is the main active stabilizer when the humerus is abducted and externally rotated. Conservative treatment of anterior shoulder instability therefore aims at strengthening this muscle. Empirical models, however, have questioned the role of the subscapularis muscle as it has been observed to potentially support dislocation of the subluxated humeral head. METHODS: Ten human shoulders were loaded with an anterior dislocating force and the effect of different subscapularis tensions on humeral translation was measured with the Motion Analysis system, for the abducted and externally rotated arm and neutral positions. Also, lines of action of the subscapularis segments were measured on a 3D epoxy model. FINDINGS: Shoulders in which the humeral head migrated antero superiorly under an external antero-inferior load were observed to dislocate under simulated active subscapularis tension in both positions. In contrast, shoulders in which the head migrated antero-inferiorly remained stable. Twice as many specimens dislocated in the abducted - externally rotated position than in the neutral position. The change in line of action of the subscapularis may account for this change. INTERPRETATION: Exercises alone are unlikely to be adequate for all patients with anterior instability symptoms. Passive motion pattern of the humeral head might serve as an indicator as to whether the effect of strengthening the subscapularis might stabilize a shoulder without further operation. Development of a clinical test based on these findings might differentiate the non-operative from operative candidates among patients presenting with anterior instability of the shoulder. PMID- 17346866 TI - Trunk extensor muscles fatigue affects undisturbed postural control in young healthy adults. AB - BACKGROUND: The purpose of this study was to investigate the effects of trunk extensor muscles fatigue on undisturbed postural control in young healthy adults. METHODS: Fifteen university students were asked to stand upright as immobile as possible with their eyes closed in two conditions of Fatigue and No fatigue of the trunk extensor muscles. Muscular fatigue was achieved by performing trunk repetitive extensions until maximal exhaustion. Centre of foot pressure displacements, recorded using a force platform, were used to compute the motions of the vertical projection of the centre of gravity and those of the difference between the centre of pressure and those of the difference between the centre of pressure and the vertical projection of the centre of gravity. These motions were processed through space-time and frequency domain analyses. FINDINGS: Larger centre of pressure minus centre of gravity and centre of gravity motions in the Fatigue than No fatigue condition are observed along both the medio-lateral and antero-posterior axes, this effect being more accentuated along the antero posterior axis. INTERPRETATION: The present findings suggest that trunk extensor muscles fatigue deteriorates undisturbed stance control, yielding, along the antero-posterior axis mainly, (1) a greater neuromuscular requirements for ensuring standing control, as indicated by the increased centre of pressure minus centre of gravity motions, and (2) a deterioration of postural performance, as indicated by the increased centre of gravity motions. PMID- 17346867 TI - Use of background inorganic arsenic exposures to provide perspective on risk assessment results. AB - Background exposures provide perspective for interpreting calculated health risks associated with naturally occurring substances such as arsenic. Background inorganic arsenic intake from diet and water for children (ages 1-6 years) and all ages of the U.S. population was modeled stochastically using consumption data from USDA, published data on inorganic arsenic in foods, and EPA data on arsenic in drinking water. Mean and 90th percentile intakes for the U.S. population were 5.6 and 10.5 microg/day, assuming nationwide compliance with the 10 microg/L U.S. drinking water standard. Intakes for children were slightly lower (3.5 and 5.9 microg/day). Based on the current EPA cancer slope factor for arsenic, estimated lifetime risks associated with background diet and water at the mean and 90th percentile are 1 per 10,000 and 2 per 10,000, respectively. By comparison, reasonable maximum risks for arsenic in soil at 20 (higher typical background level) and 100mg/kg are 4 per 100,000 and 2 per 10,000, using EPA default exposure assumptions. EPA reasonable maximum estimates of arsenic exposure from residential use of treated wood are likewise within background intakes. These examples provide context on how predicted risks compare to typical exposures within the U.S. population, thereby providing perspective for risk communication and regulatory decision-making on arsenic in the environment and in consumer products. PMID- 17346868 TI - Failure to confirm an association between the PLXNA2 gene and schizophrenia in a Japanese population. AB - Plexins are receptors for multiple classes of semaphorins, either alone or in combination with neuropilins. Plexins participate in many cellular events that include axonal repulsion, axonal attraction, cell migration, axon pruning, and synaptic plasticity. PLXNA2 maps to chromosome 1q32. Several linkage studies reported schizophrenia susceptibility loci in the 1q22-42 region. A recent study reported that intronic single nucleotide polymorphisms (SNPs) of PLXNA2 were associated with schizophrenia in a European American population. We attempted to replicate this finding in a Japanese sample of 336 patients with schizophrenia and 304 controls. In addition, we examined 3 non-synonymous SNPs (Arg5Gln, GLn57Arg, and Ala267Thr) in PLXNA2. Genotyping was performed by the TaqMan allelic discrimination assay. There was no significant difference in genotype or allele distribution of either the 4 intronic SNPs or the 3 non-synonymous SNPs between patients and controls. Furthermore, haplotype-based analyses did not provide evidence for an association. These results suggest that PLXNA2 may not play a major role in the development of schizophrenia in our Japanese sample. PMID- 17346869 TI - Neurocardiology. PMID- 17346870 TI - The feasibility of a regional cardiac arrest receiving system. AB - BACKGROUND: Patients suffering out-of-hospital cardiac arrest (OOHCA) are generally transported to the closest ED, presumably to expedite a hospital level of care and improve the chances of return for spontaneous circulation (ROSC) or provide post-resuscitative care for patients with prehospital ROSC. As hospital based therapies for survivors of OOHCA are identified, such as hypothermia and emergency primary coronary interventions (PCI), certain hospitals may be designated as cardiac arrest receiving facilities. The safety of bypassing non designated facilities with such a regional system is not known. OBJECTIVES: To explore the potential ED contribution in OOHCA victims without prehospital ROSC and document the relationship between transport time and outcome in patients with prehospital ROSC. METHODS: This was a prospective, observational study conducted in a large, urban EMS system over an 18-month period. Data were collected using the Utstein template for OOHCA. The incidence of prehospital ROSC was calculated for patients who were declared dead on scene, transported but died in the ED, died in the hospital, and survived to hospital discharge. The relationship between transport time and survival was also explored for patients with prehospital ROSC. RESULTS: A total of 1141 cardiac arrest patients were enrolled over the 18-month period. A strong association between prehospital ROSC and final disposition was observed (chi-square test for trend p<0.001). Only two patients who survived to hospital discharge did not have prehospital ROSC. Mean transport times were not significantly different for patients with prehospital ROSC who were declared dead in the ED (8.3min), died following hospital admission (7.8min), and survived to hospital discharge (8.5min). Outcomes in patients with prehospital ROSC who had shorter (7min or less) versus longer transport times were similar, and receiver-operator curve analysis indicated no predictive ability of transport time with regard to survival to hospital admission (area under the curve=0.52). CONCLUSIONS: In this primarily urban EMS system, the vast majority of survivors from OOHCA are resuscitated in the field. A relationship between transport time and survival to hospital admission or discharge was not observed. This supports the feasibility of developing a regional cardiac arrest system with designated receiving facilities. PMID- 17346871 TI - The safety of ultrasound-guided oocyte pick-up in IVF patients with haemostatic disorders. PMID- 17346872 TI - Functional tissue pulsatility imaging of the brain during visual stimulation. AB - Functional tissue pulsatility imaging is a new ultrasonic technique being developed to map brain function by measuring changes in tissue pulsatility as a result of changes in blood flow with neuronal activation. The technique is based in principle on plethysmography, an older, nonultrasound technology for measuring expansion of a whole limb or body part as a result of perfusion. Perfused tissue expands by a fraction of a percent early in each cardiac cycle when arterial inflow exceeds venous outflow, and it relaxes later in the cardiac cycle when venous drainage dominates. Tissue pulsatility imaging (TPI) uses tissue Doppler signal processing methods to measure this pulsatile "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. A feasibility study was conducted to determine if TPI could be used to detect regional brain activation during a visual contrast-reversing checkerboard block paradigm study. During a study, ultrasound data were collected transcranially from the occipital lobe as a subject viewed alternating blocks of a reversing checkerboard (stimulus condition) and a static, gray screen (control condition). Multivariate analysis of variance was used to identify sample volumes with significantly different pulsatility waveforms during the control and stimulus blocks. In 7 of 14 studies, consistent regions of activation were detected from tissue around the major vessels perfusing the visual cortex. PMID- 17346874 TI - Examples of in vivo blood vector velocity estimation. AB - In this paper, a case study of in-vivo blood vector velocity images of the carotid artery are presented. The transverse oscillation (TO) method for blood vector velocity estimation has been used to estimate the vector velocities. The carotid arteries of three healthy volunteers are scanned in-vivo at three different positions by experienced sonographers. The scanning regions are: 1) the common carotid artery at 88 degrees beam to flow angle, 2) the common carotid artery and the jugular vein at approximately 90 degrees beam to flow angle and 3) the bifurcation of the carotid artery. The resulting velocity estimates are displayed as vector velocity images, where the velocity vector is superimposed on a B-mode image showing the tissue structures. The volume flow is found for case 1) and when compared with MRI from the literature, a bias of approximately approximately 20% is found. The maximum flow velocity within the carotid artery is found to be 0.8 m/s, which is normal for a healthy person. In case 3), the estimated vector velocities are compared with numerical simulations. Qualitatively similar flow pattern can be seen in both simulations and in the vector velocity images. Furthermore, a vortex is identified in the carotid sinus at the deceleration phase after the peak systole. This vortex is seen in all of the three acquired cardiac cycles. PMID- 17346873 TI - Effects of isoflurane on coronary blood flow velocity in young, old and ApoE(-/-) mice measured by Doppler ultrasound. AB - The commonly used anesthetic agent isoflurane (ISO) is a potent coronary vasodilator that could potentially be used in the assessment of coronary reserve, but its effects on coronary blood flow in mice are unknown. Coronary reserve is reduced by age, coronary artery disease and other cardiac pathologies in man, and some of these conditions can now be modeled in mice. Accordingly, we used Doppler ultrasound to measure coronary flow velocity in mice anesthetized with low (1%) and high (2.5%) levels of ISO to generate baseline (B) and elevated hyperemic (H) coronary flows, respectively. A 20-MHz Doppler probe was mounted in a micromanipulator and pointed trans-thoracically toward the origin of the left main coronary arteries of 10 6-wk (Young [Y]), 10 2-y (Old [O]) and 20 2-y apolipoprotein-E null (ApoE(-/-)) atherosclerotic (A) mice. In each mouse, we measured (B) and (H) peak diastolic velocities. B was 35.4 +/- 1.4 cm/s (Y), 24.8 +/- 1.6 (O) and 51.7 +/- 6.4 (A); H was 83.5 +/- 1.3 (Y), 86.5 +/- 1.9 (O) and 120 +/- 16.9 (A) and H/B was 2.4 +/- 0.1 (Y), 3.6 +/- 0.2 (O) and 2.5 +/- 0.2 (A). The differences in baseline velocities and H/B between O and Y and between A and O were significant (p < 0.01), whereas the differences in hyperemic velocities were not (p > 0.05). H/B was higher in old mice as a result of decreased baseline flow rather than increased hyperemic flow velocity. In contrast, ApoE(-/-) mice have increased baseline and hyperemic velocities, perhaps because of coronary lesions. The differences in baseline velocities between young and old mice could be the result of age-related changes in basal metabolism or to differential sensitivity to isoflurane. We conclude that Doppler ultrasound combined with coronary vasodilation via isoflurane could provide a convenient and noninvasive method to estimate coronary reserve in mice, but also that care must be taken when assessing coronary flow in mice under isoflurane anesthesia because of its potent coronary vasodilator properties. PMID- 17346875 TI - Analysis of fluctuation in protein abundance without promoter regulation based on Escherichia coli continuous culture. AB - Fluctuation of protein abundance of isogenic Escherichia coli cells in uniform environment was studied. Based on a continuous culture system, which provides homogeneous culture environment, we investigated the fluctuation in GlnA protein abundance regardless of known glnALG promoter regulation. As results by flow cytometer, we found that the GlnA protein abundance in the cells exhibit a large fluctuation, even though GlnA protein is an essential factor for cell growth and the environment is homogeneous. Furthermore, among several steady states, transient processes of such heterogeneous cell population were investigated, by changing the environmental conditions. The results showed that the expression of GlnA protein can be controlled, depending on its necessity, even though there is no known regulatory machinery. These results may provide a clue to understand the nature of regulation of protein expression dynamics with the stochastic fluctuation. PMID- 17346876 TI - AN-113, a novel prodrug of 4-phenylbutyrate with increased anti-neoplastic activity in glioma cell lines. AB - Butyroyloxymethyl-4-phenylbutyrate (AN-113) is a novel HDACI that releases potent anti-neoplastic derivatives upon intracellular hydrolysis. The precursor of AN 113, 4-phenylbutyrate has shown promising results in a Phase I study of gliomas, and we hypothesized that AN-113 offers significant advantages over the parent drug. AN-113 demonstrates selective in vitro cytotoxicity against malignant cells while sparing normal astrocytes, effective at doses over 20-fold lower than 4 phenylbutyrate. Combining AN-113 and radiation results in additive therapeutic effects. Enthusiasm is lent to this approach by the ability of AN-113 to efficiently kill glioma cells, its bioavailability and potency when administered orally, its capacity to cross the blood-brain barrier, and its effectiveness in combination with radiation. PMID- 17346877 TI - Retention of radium from thermal waters on sand filters and adsorbents. AB - This study was focussed on laboratory experiences of retention of radium from one thermal water on sand filters and adsorbents, trying to find an easy method for the elimination in drinkable waters polluted with this natural radio-nuclide. A thermal water from Cantabria (Spain) was selected for this work. Retention experiences were made with columns of 35 mm of diameter containing 15 cm layers of washed river sand or 4 cm layers of zeolite A3, passing known volumes of thermal water at flows between 4 and 40 ml/min with control of the retained radium by determining the amount in the water after the treatment. The statistical analysis of data suggests that retention depends on the flow and the volume passed through the columns. As additional adsorbents were used kaolin and a clay rich in illite. Jar-test experiences were made agitating known weights of adsorbents with the selected thermal water, with addition of flocculants and determination of radium in filtrated water after the treatment. Data suggest that retention is related to the weight of adsorbent used, but important quantities of radium seem remain in solution for higher amounts of adsorbents, according to the statistical treatment of data. The elution of retained radium from columns or adsorbents, previously used in experiences, should be the aim of a future research. PMID- 17346878 TI - Distribution of arsenic in groundwater in the area of Chalkidiki, Northern Greece. AB - An integrate study aiming at the occurrence and distribution of arsenic in groundwater in the area of Chalkidiki, Northern Greece has been carried out. Groundwater samples from public water supply wells and private wells were analysed for arsenic and other quality parameters (T, pH, EC, Ca, Mg, Na, K, Cl, HCO(3), NO(3), SO(4), B, Fe, Mn). Arsenic showed high spatial variation; ranged from 0.001 to 1.840mg/L. Almost 65% of the examined groundwaters exhibit arsenic concentrations higher than the maximum concentration limit of 0.010mg/L, proposed for water intended for human consumption. Correlation analysis and principal component analysis were employed to find out possible relationships among the examined parameters and groundwater samples. Arsenic is highly correlated with potassium, boron, bicarbonate, sodium, manganese and iron suggesting common geogenic origin of these elements and conditions that enhance their mobility. Three groups of groundwater with different physicochemical characteristics were found in the study area: (a) groundwater with extremely high arsenic concentrations (1.6-1.9mg/L) and high temperature (33-42 degrees C) from geothermal wells, (b) groundwater with relatively high arsenic concentrations (>0.050mg/L), lower temperatures and relatively high concentrations of major ions, iron and manganese and, (c) groundwater with low arsenic concentrations that fulfil the proposed limits for dinking water. PMID- 17346879 TI - Simultaneous sorption and desorption of Cd, Cr, Cu, Ni, Pb, and Zn in acid soils I. Selectivity sequences. AB - The sorption and desorption of six heavy metals by and from the surface or immediately subsurface horizons of eleven acid soils of Galicia (N.W. Spain) were characterized by means of batch experiments in which the initial sorption solution contained identical mass concentrations of each metal. Concentration dependent coefficients K(d) were calculated for the distribution of the metals between the soil and solution phases, and the values obtained for initial sorption solution concentrations of 100mgL(-1) of each metal (K(d100)) were used, for each soil, to order the metals as regards their sorption and retention. Pb and Cu were sorbed and retained to a greater extent than Cd, Ni or Zn, which had low K(d100) values. Pb was sorbed more than any other metal. Cr was generally sorbed only slightly more than Cd, Ni or Zn, but was strongly retained, with K(d100) (retention) values greater than those of Pb and Cu in soils with very low CEC (<3cmol((+))kg(-1)). The sorption of Pb and Cu correlated with organic matter content, while the retention of these and the other metals considered appeared to depend on clay minerals, especially kaolinite, gibbsite, and vermiculite. PMID- 17346880 TI - WITHDRAWN: The flow-injection spectrophotometric detection of Thallium (III) in environmental and biological samples using newly synthesized reagent. AB - This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause. PMID- 17346881 TI - Ammonium removal from landfill leachate by anodic oxidation. AB - The feasibility of removing ammonium from landfill leachates by electrochemical oxidation was studied. Raw leachates and biologically/physico-chemically pretreated leachates from a municipal landfill site were treated. Boron doped diamond was used as anode and stainless steel as cathode, both electrodes with an area of 70 cm(2). The effects of the applied current density (15-90 mA cm(-2)), the initial ammonium concentration (480-2000 mg L(-1)), and the initial chloride concentration were experimentally studied. Total ammonium removal was obtained after 360 min of processing and almost half of the initial ammonium nitrogen was oxidized to nitrate. On the other hand, the concentration of chloride enhanced the rate of ammonium oxidation. In addition, the amount of N-NH(4)(+) transformed into N-NO(3)(-) decreased when additional chloride was provided. PMID- 17346882 TI - Association analysis of ATF4 and ATF5, genes for interacting-proteins of DISC1, in bipolar disorder. AB - Disrupted in schizophrenia 1 (DISC1) and its molecular cascade are implicated in the pathophysiology of schizophrenia and bipolar disorder. As interacting proteins with DISC1, Nudel, ATF4, ATF5, LIS1, alpha-tubulin, PDE4B, eIF3, FEZ1, Kendrin, MAP1A and MIPT3 were identified. We previously showed the down regulation of ATF5 in the lymphoblastoid cells derived from affected co-twin of monozygotic twins discordant for bipolar disorder. We also suggested the contribution of endoplasmic reticulum stress response pathway to the illness, and ATF4 is one of major components in the pathway. Truncated mutant DISC1 reportedly cannot interact with ATF4 and ATF5. These findings suggest the role of these genes in the pathophysiology of bipolar disorder. In this study, we tested genetic association of ATF4 and ATF5 genes with bipolar disorder by a case control study in Japanese population (438 patients and 532 controls) and transmission disequilibrium test in 237 trio samples from NIMH Genetics Initiative Pedigrees. We also performed gene expression analysis in lymphoblastoid cells. We did not find any significant association in both genetic study and expression analysis. By the exploratory haplotype analysis, nominal association of ATF4 with bipolar II patients was observed, but it was not significant after correction of multiple testing. Contribution of common variations of ATF4 and ATF5 to the pathophysiology of bipolar disorder may be minimal if any. PMID- 17346883 TI - Estradiol replacement increases the low-density lipoprotein receptor related protein (LRP) in the mouse brain. AB - Numerous epidemiology studies have shown protective effects of hormone therapy (HT) on chronic neurological diseases. We have proposed that some of the neuroprotective effects of estrogen are mediated by apolipoprotein E (apoE). Polymorphisms of receptors for apoE modify the risk for dementia. To our knowledge, no reports exist showing CNS effects of estrogen replacement on members of the low-density lipoprotein receptor family. The current study focused on the effect of estradiol-17beta (E2) replacement on protein expression of two members of the receptor family, the low-density lipoprotein receptor (LDL-r) and low-density lipoprotein receptor related protein (LRP) in ovariectomized mice. Five days of E2 replacement significantly increased LRP expression in the hippocampus, olfactory bulb and neocortex but not in cerebellum. In contrast, E2 treatment decreased LDL-r protein expression in olfactory bulb. HT modification of both apoE and LRP could have wide-spread effects on cellular function given LRP's manifold signaling functions. PMID- 17346885 TI - Amitriptyline preserves morphine's antinociceptive effect by regulating the glutamate transporter GLAST and GLT-1 trafficking and excitatory amino acids concentration in morphine-tolerant rats. AB - The present study was undertaken to examine the effect of amitriptyline on the antinociceptive effect of morphine and its underlying mechanisms in regulating glutamate transporters trafficking in morphine-tolerant rats. Long-term morphine infusion induced antinociceptive tolerance and down-regulation of glutamate transporters (GTs), GLAST, GLT-1, and EAAC1, expression in the rat spinal cord dorsal horn. Acute amitriptyline treatment potentiated morphine's antinociceptive effect, with a 5.3-fold leftward shift of morphine's dose-response curve in morphine-tolerant rats, and this was associated with GLAST and GLT-1 trafficking onto the cell surface. Similar to our previous studies, morphine challenge (10 microg/10 microl, i.t.) significant by increased the excitatory amino acids (EAAs) aspartate and glutamate level in the CSF dialysates of morphine-tolerant rats. Acute amitriptyline treatment not only suppressed this morphine-evoked EAA release, but further reduced the EAA concentration than baseline level. Furthermore, long-term morphine infusion up-regulated PKA and PKC protein expression in the spinal cord dorsal horn, while amitriptyline inhibited the increase in expression of phospho-PKA, PKCalpha, PKCbetaII, and PKCgamma. In morphine-tolerant rats, acute treatment with PKA inhibitor H89 and PKC inhibitor Go6805 attenuated morphine tolerance and the morphine-induced CSF glutamate and aspartate elevation, and induced trafficking of GLAST and GLT-1 from cytosol onto the cell surface. These results show that acute amitriptyline treatment preserved morphine's antinociceptive effect in morphine-tolerant rats; the mechanisms may be involved in inhibition of phospho-PKA and PKC expression, and thus inducing the GLAST and GLT-1 trafficking onto glial cell surface which enhances the EAA uptake from the synaptic cleft and reduces EAA concentration in the spinal CSF. PMID- 17346884 TI - CART peptides increase 5-hydroxytryptamine in the dorsal raphe and nucleus accumbens of freely behaving rats. AB - Cocaine and amphetamine-regulated transcript peptides (CART) are implicated in the antidepressant effect. This may involve in 5-hydroxytryptamine (5-HT) in the CNS. The aim of the present studies was to investigate the effect of CART peptides on extracellular 5-HT in the dorsal raphe nucleus (DRN) and nucleus accumbens (NAcc) using a microdialysis approach in freely behaving rats. Reverse infusion of CART61-102 in the DRN produced a concentration (10-100 microM) dependent increase in 5-HT in the DRN. Similarly, CART62-76 (10-100 microM) infused into the DRN and NAcc elevated 5-HT in the DRN and NAcc, respectively. Thus, CART increases extracellular 5-HT in both the DRN and NAcc. In addition, infusion of CART62-76 (100 microM) in the DRN produced a significant increase in 5-HT in the NAcc, implying an existence of CART receptors responsible for the depolarization-dependent release. In summary, the results of the present studies suggest that CART peptides may have an antidepressant effect through increases in extracellular 5-HT. PMID- 17346886 TI - Oral and spinal melatonin reduces tactile allodynia in rats via activation of MT2 and opioid receptors. AB - The antiallodynic effect of melatonin after intrathecal (it) and oral administration as well as the possible participation of MT(2) and opioid receptors in melatonin-induced antiallodynia in neuropathic rats were assessed. Ligation of the L5/L6 spinal nerves produced a clear-cut tactile allodynia in the rats. Intrathecal (3-100 microg) and oral (37.5-300 mg/kg) administration of melatonin decreased tactile allodynia induced by spinal nerve ligation. Intrathecal administration of the preferential MT(2) receptor antagonist luzindole (1-100 microg), but not vehicle, significantly diminished in a dose dependent manner the antiallodynic effect induced by melatonin (100 microg, it). Oral (0.01-1mg/kg) or intrathecal (0.1-10 microg) administration of the highly selective MT(2) receptor antagonist 4P-PDOT diminished the antiallodynic activity induced by oral (150 mg/kg) or intrathecal (100 microg) administration of melatonin, respectively. Subcutaneous (1mg/kg) or intrathecal (0.5-50 microg) treatment with naltrexone, but not vehicle, significantly diminished the antiallodynic effect induced by oral (150 mg/kg) or intrathecal (100 microg) administration of melatonin. Oral melatonin (150 mg/kg)-induced antiallodynia was partially reduced by the spinal administration of 4P-PDOT (10 microg). Moreover, the spinal effect of melatonin (100 microg) was significantly reduced by the combination 4P-PDOT (0.1 microg)-naltrexone (0.5 microg). At the greatest tested doses, the antagonist drugs did not modify tactile allodynia in neuropathic rats. Melatonin (100 microg or 300 mg/kg) did not affect motor co-ordination in the rotarod test. Results indicate that melatonin reduces tactile allodynia in neuropathic rats after intrathecal and oral administration. Moreover, data suggest the participation of spinal MT(2) and opioid receptors in the melatonin induced antiallodynic effect in this model. PMID- 17346887 TI - Trigeminal small-fibre function assessed with contact heat evoked potentials in humans. AB - Contact heat stimuli have been reported to excite mechano-thermal nociceptors and to evoke brain potentials (CHEPs) from the limbs. We investigated whether contact heat evokes reproducible CHEPs from the trigeminal territory and may prove a reliable diagnostic tool in facial neuropathic pain. We applied contact heat stimuli to the perioral and supraorbital regions; CHEPs were recorded from the vertex in 20 controls and 2 patients with facial neuropathic pains, and reflex responses from the orbicularis oculi and masticatory muscles in 5 controls. We studied the correlation between CHEP data and perceptive ratings, site of stimulation, and age. Finally, we compared CHEPs with laser evoked potentials (LEPs). Contact heat stimuli at 51 degrees C evoked vertex potentials consisting of an NP complex similar to that elicited by laser pulses, though with a latency some 100-ms longer. Perioral stimulation yielded higher pain intensity ratings, shorter latency and larger amplitude CHEPs than supraorbital stimulation. CHEP data correlated significantly with age. Contact heat stimuli at 53 degrees C evoked a blink-like response in the relaxed orbicularis oculi muscle and a silent period in the contracted masseter muscle. In patients with facial neuropathic pain the CHEP abnormalities paralleled those seen with LEPs. We were unable to achieve reproducible signals related to C-receptor stimulation by contact heat stimuli at 41 degrees C in the ten subjects in whom they were tested. Contact heat stimulation, as well as laser stimulation, easily yields large-amplitude brain potentials and nociceptive reflexes, both related to the Adelta input. However CHEPs are not suitable for C-fibres potentials recording. PMID- 17346888 TI - Hydrogen sulfide as a novel nociceptive messenger. AB - Hydrogen sulfide (H(2)S), an endogenous gasotransmitter, modulates various biological events such as inflammation in the mammalian body. The present study investigated possible involvement of H(2)S in peripheral nociceptive processing. Intraplantar (i.pl.) administration of NaHS, a H(2)S donor, produced prompt hyperalgesia in rats, accompanied by expression of Fos in the spinal dorsal horn. The H(2)S-evoked hyperalgesia was blocked by 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB), an oxidizing agent, or ethosuximide and mibefradil, T-type Ca(2+) channel inhibitors. L-Cysteine, an endogenous source for H(2)S, given i.pl., also elicited hyperalgesia, an effect being abolished by DL-propargylglycine (PPG) and beta-cyanoalanine (BCA), inhibitors of cystathionine-gamma-lyase, a H(2)S synthesizing enzyme. PPG and/or BCA partially inhibited the hyperalgesia induced by i.pl. lipopolysaccharide, an effect being reversed by i.pl. NaHS. In the patch clamp study using undifferentiated NG108-15 cells that express T-type, but not other types, of Ca(2+) channels, NaHS enhanced the currents through the T-type channels, an effect being blocked by DTNB. Thus, H(2)S appears to function as a novel nociceptive messenger through sensitization of T-type Ca(2+) channels in the peripheral tissues, particularly during inflammation. PMID- 17346889 TI - Health care practitioners' attitudes and beliefs about low back pain: a systematic search and critical review of available measurement tools. AB - The attitudes and beliefs that health care practitioners (HCPs) hold about back pain have been shown to affect the advice they provide to patients seeking healthcare. In order to develop a questionnaire for a national survey of attitudes, beliefs and practice behaviour of HCPs about back pain, a systematic review of available measurement tools was undertaken. Measurement tools were identified from a systematic search of databases (Medline, Embase, CINAHL, Psychinfo, AMED and British Nursing Index) in the English language for papers published from January 1990 to October 2006. Quality criteria were applied to each of the tools by two independent reviewers. The initial search strategy generated a total of 5269 references. Following assessment of titles and abstracts, 12 papers describing five tools were identified for inclusion in the review. The tools were the Attitudes to Back Pain scale for musculoskeletal practitioners (ABS.mp), a fear avoidance beliefs tool, the Fear Avoidance Beliefs Questionnaire (FABQ) adapted for HCPs, the Health Care Providers' Pain and Impairment Relationship Scale (HC-PAIRS) and the Pain Attitudes and Beliefs Scale for Physiotherapists (PABS.PT). The HC-PAIRS and PABS.PT have undergone the most thorough testing to date, but gaps in the properties of all the tools remain, particularly test-retest reliability and responsiveness. This review identified only five tools and demonstrated limited reporting of their validity and reliability. Further development and testing of existing tools should be a priority to ensure they are robust and valid measures of attitudes and beliefs of HCPs about back pain. PMID- 17346890 TI - Direct electron imaging in electron microscopy with monolithic active pixel sensors. AB - A new imaging device for dynamic electron microscopy is in great demand. The detector should provide the experimenter with images having sufficient spatial resolution at high speed. Immunity to radiation damage, accumulated during exposures, is critical. Photographic film, a traditional medium, is not adequate for studies that require large volumes of data or rapid recording and charge coupled device (CCD) cameras have limited resolution, due to phosphor screen coupling. CCD chips are not suitable for direct recording due to their extreme sensitivity to radiation damage. This paper discusses characterization of monolithic active pixel sensors (MAPS) in a scanning electron microscope (SEM) as well as in a transmission electron microscope (TEM). The tested devices were two versions of the MIMOSA V (MV) chip. This 1M pixel device features pixel size of 17 x 17 microm(2) and was designed in a 0.6 microm CMOS process. The active layer for detection is a thin (less than 20 microm) epitaxial layer, limiting the broadening of the electron beam. The first version of the detector was a standard imager with electronics, passivation and interconnection layers on top of the active region; the second one was bottom-thinned, reaching the epitaxial layer from the bottom. The electron energies used range from a few keV to 30 keV for SEM and from 40 to 400 keV for TEM. Deterioration of the image resolution due to backscattering was quantified for different energies and both detector versions. PMID- 17346891 TI - Modulation of hippocampal long-term potentiation by slow increases in ethanol concentration. AB - To determine how acute ethanol intoxication may alter memory processing, we examined the effects of stepwise increases in ethanol on long-term potentiation (LTP) in rat hippocampal slices. LTP was inhibited by acute administration of 60 mM ethanol, but was readily induced if ethanol was increased gradually to 60 mM over 75 min. Administration of 2-amino-5 phosphonovalerate (APV), an N-methyl-D aspartate receptor (NMDAR) antagonist, during the stepwise increase in ethanol inhibited LTP, suggesting involvement of NMDARs in the development of tolerance. However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol. Ethanol tolerant LTP was inhibited by thapsigargin, suggesting a major role for intracellular calcium release in this form of plasticity. The unique properties of ethanol-tolerant LTP suggest that memories formed during binge drinking are not acquired by standard synaptic mechanisms and that acute tolerance may involve the induction of novel mechanisms to maintain function. PMID- 17346892 TI - Glycine receptors are functionally expressed on bullfrog retinal cone photoreceptors. AB - Using immunocytochemical and whole cell recording techniques, we examined expression of glycine receptors on bullfrog retinal cone photoreceptors. Immunofluorescence double labeling experiments conducted on retinal sections and isolated cell preparations showed that terminals and inner segments of cones were immunoreactive to both alpha1 and beta subunits of glycine receptors. Moreover, application of glycine induced a sustained inward current from isolated cones, which increased in amplitude in a dose-dependent manner, with an EC50 (concentration of glycine producing half-maximal response) of 67.3+/-4.9 microM, and the current was blocked by the glycine receptor antagonist strychnine, but not 5,7-dichlorokynurenic acid (DCKA) of 200 microM, a blocker of the glycine recognition site at the N-methyl-D-aspartate (NMDA) receptor. The glycine-induced current reversed in polarity at a potential close to the calculated chloride equilibrium potential, and the reversal potential was changed as a function of the extracellular chloride concentration. These results suggest that strychnine sensitive glycine receptors are functionally expressed in bullfrog cones, which may mediate signal feedback from glycinergic interplexiform cells to cones in the outer retina. PMID- 17346893 TI - In vivo brain-derived neurotrophic factor release and tyrosine kinase B receptor expression in the supraoptic nucleus after osmotic stress stimulus in rats. AB - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family involved in plasticity and neuroprotective processes. In recent years, we have reported the presence of BDNF mRNA in the supraoptic nucleus (SON) as well its sensitivity to osmotic stress. The rat SON is a relatively homogenous nucleus mainly consisting of magnocellular soma with their dendritic processes. BDNF may be released from dendrites to the extracellular space to stimulate tyrosine kinase (Trk) B receptors which are hypothetically present on these subcellular SON compartments. The main goal of this work was thus to study the presence and the in vivo BDNF-IR release from SON using the push-pull perfusion technique following systemic (i.p.) or local (within the SON) osmotic stimulation. BDNF was detected by immunocytochemistry and its release was measured by immunological assay (ELISA). Likewise, TrkB receptor localization in the SON-mRNA and their respective proteins-were studied by in situ hybridization and immunohistofluorescence techniques, respectively. Phosphorylation of CREB was detected by immunohistofluorescence. We present here direct evidence of in vivo dendritic BDNF release from SON which is highly sensitive to osmotic stress. The osmotic response latency period clearly depends on the mode of stimulus application (210 min for i.p. route vs. 15 min for intra-SON administration). The fact that BDNF is released as a very rapid peak when osmotic stimulation is locally applied is strong evidence in favor of an intra-SON origin of this secretion. Osmotic stress also increased phosphorylated cAMP response element binding protein immunoreactivity in the SON. In addition, we show in control rats that truncated forms of tyrosine kinase B receptor 2 mRNA represent the most abundant messenger in the SON as compared with brain-derived neurotrophic factor full-length catalytic receptor or truncated forms of tyrosine kinase B receptor 1 mRNA. In conclusion, it is likely that BDNF and their receptors are involved in neuronal plasticity changes induced by osmotic stress in the SON. PMID- 17346894 TI - Group II metabotropic glutamate receptors reduce excitatory but not inhibitory neurotransmission in rat barrel cortex in vivo. AB - Group II metabotropic (mGlu) receptors are known to play an important role in regulating the release of excitatory transmitter in a number of brain areas. Previous experiments demonstrated that (1S,3R)-1-aminocyclopentane-1,3 dicarboxylic acid (1S,3R-ACPD) depressed excitatory transmission in the adult rat barrel cortex. Here we show, using in vivo extracellular single unit recordings and iontophoretic application of drugs, that selective activation of Group II mGlu receptors depresses excitatory but not inhibitory transmission. The selective Group II receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) had similar depressant effects to 1S,3R-ACPD on tactile evoked responses of rapidly adapting neurons. The depressant effects were seen on shorter latency (<12 ms) responses, were most pronounced in layers 3-4 (and 5b for 2R,4R-APDC only), and were reversibly antagonized by the Group II receptor antagonist (2S)-alpha-ethylglutamic acid (EGLU) relative to depressions produced by iontophoretic GABA. Where 1S,3R-ACPD and 2R,4R-APDC depressed excitatory transmission, there was little or no effect on postsynaptic excitations produced by iontophoretic AMPA--a result that supports a presynaptic location of Group II receptors on excitatory terminals. To assess the possible involvement of Group II mGlu receptors in the modulation of inhibition, we studied the effect of iontophoretic 1S,3R-ACPD in a condition-test protocol. The results contrasted markedly from those previously observed using the Group III agonist L(+)-2-amino 4-phosphonobutyric acid in that activation of Group II receptors using 1S,3R-ACPD did not modulate inhibition. Therefore our results show that Group II mGlu receptors play an important role in modulating excitatory, but not inhibitory, transmission. We propose that the Group II mGlu receptors are located on excitatory terminals, and act as autoreceptors. Their role appears to be important in the early stages of cortical processing, by keeping excitatory inputs within specified physiological limits, and possibly by mediating depression evidenced during synaptic plasticity. PMID- 17346895 TI - Psychophysical evidence for two routes to suppression before binocular summation of signals in human vision. AB - Visual mechanisms in primary visual cortex are suppressed by the superposition of gratings perpendicular to their preferred orientations. A clear picture of this process is needed to (i) inform functional architecture of image-processing models, (ii) identify the pathways available to support binocular rivalry, and (iii) generally advance our understanding of early vision. Here we use monoptic sine-wave gratings and cross-orientation masking (XOM) to reveal two cross oriented suppressive pathways in humans, both of which occur before full binocular summation of signals. One is a within-eye (ipsiocular) pathway that is spatially broadband, immune to contrast adaptation and has a suppressive weight that tends to decrease with stimulus duration. The other pathway operates between the eyes (interocular), is spatially tuned, desensitizes with contrast adaptation and has a suppressive weight that increases with stimulus duration. When cross oriented masks are presented to both eyes, masking is enhanced or diminished for conditions in which either ipsiocular or interocular pathways dominate masking, respectively. We propose that ipsiocular suppression precedes the influence of interocular suppression and tentatively associate the two effects with the lateral geniculate nucleus (or retina) and the visual cortex respectively. The interocular route is a good candidate for the initial pathway involved in binocular rivalry and predicts that interocular cross-orientation suppression should be found in cortical cells with predominantly ipsiocular drive. PMID- 17346896 TI - GABAergic processes in the mesencephalic tegmentum modulate the occurrence of active (rapid eye movement) sleep in guinea pigs. AB - The ventrolateral subdivision of the periaqueductal gray (vlPAG) and the adjacent dorsal mesencephalic reticular formation (dMRF) are involved in the modulation of active (rapid eye movement) sleep (AS). In order to determine the effects on AS of the suppression of neuronal activity in these regions, muscimol, a GABA receptor A (GABA(A)) receptor agonist, and bicuculline, a GABA(A) receptor antagonist, were microinjected bilaterally in guinea pigs and the states of sleep and wakefulness were examined. The main effect of muscimol was an increase in AS; this increase occurred in conjunction with a reduction in the time spent in wakefulness. The powerful effect of muscimol was striking especially when considering the small amount of naturally-occurring AS that is present in this species. Additional observable effects that were induced by muscimol were: 1) long lasting episodes of hypotonia/atonia during wakefulness and quiet sleep that included a lack of extensor tone in the hind limbs, and 2) frequently occurring cortical spindles, similar to those observed during naturally-occurring quiet sleep (sleep spindles), that were present during wakefulness. Conversely, bilateral microinjections of bicuculline induced a prolonged state of wakefulness and blocked the effect of subsequent injections of muscimol. These data suggest that endogenous GABA acts on GABA(A) receptors within the vlPAG and dMRF to promote AS in the guinea pig. PMID- 17346897 TI - Neurotoxic lesions of the caudate-putamen on a reaching for food task in the rat: acute sensorimotor neglect and chronic qualitative motor impairment follow lateral lesions and improved success follows medial lesions. AB - Reaching for food, or skilled reaching, is used as a test of basal ganglia function in preclinical studies as well as studies of human neurological conditions. Although changes in the end-point measure of success document the effects of neurotoxic cellular damage to the caudate-putamen and its treatment in rodents, there has been no examination of the cause of change in success after neurotoxic lesions of the striatum. This objective was addressed in the present study, in which rats trained to reach for single food pellets with one forelimb, received contralateral quinolinic acid or ibotenic acid lesions of the medial and lateral caudate-putamen. Over 21 postsurgical days, reaching performance was scored for success and qualitative changes in movement elements were examined using frame-by-frame video analysis. In the acute postoperative period, extending over 3 to 4 days, the rats with lateral lesions transported their forelimb and grasped the food, but then ignored the food and did not withdraw their limb to their mouth. After recovery of the withdrawal movement, the rats displayed chronic qualitative impairments in the rotatory movements of aiming, pronating, and supinating the forepaw. Medial quinolinic lesions improved success relative to control rats and did not change qualitative aspects of limb movement. The acute dissociation between transport and withdrawal, the chronic qualitative changes in movement elements, and the differential effect of medial and lateral injury on success, support a complex contribution of the caudate-putamen to skilled reaching that includes sensorimotor neglect, and quantitative and qualitative motoric changes. PMID- 17346898 TI - Synaptic vesicle pools at diaphragm neuromuscular junctions vary with motoneuron soma, not axon terminal, inactivity. AB - Both spinal hemisection (SH) at C2 and tetrodotoxin (TTX) phrenic nerve blockade result in diaphragm muscle paralysis and inactivity of the phrenic axon terminals. However, phrenic motoneuron somata are inactive with SH but remain active with TTX phrenic nerve blockade. Neuromuscular transmission failure with repeated activation decreases following SH and increases following TTX phrenic nerve blockade, suggesting that matching (or mismatching) of somal and synaptic inactivities of phrenic motoneurons differentially regulates synaptic vesicle pools at diaphragm neuromuscular junctions. At individual type-identified rat diaphragm presynaptic terminals, the size of the releasable pool of synaptic vesicles was analyzed by fluorescence confocal microscopy of N-(3 triethylammoniumpropyl)-4-(6-(4-(diethylamino)phenyl)hexatrienyl) pyridinium dibromide (FM4-64) uptake and synaptic vesicle density at active zones was determined using transmission electron microscopy. After 14 days of SH and TTX induced diaphragm muscle inactivity, neuromuscular junction size was not different at type I or IIa fibers, but increased at type IIx and/or IIb fibers (by 51% in SH and 35% in TTX) compared with control. With SH, synaptic vesicle pool size and density increased at presynaptic terminals innervating type I or IIa fibers (17 and 63%, respectively; P<0.001) and type IIx and/or IIb fibers (41 and 31%, respectively; P<0.001) when compared with controls. Following TTX, synaptic vesicle pool size and density decreased by 64 and 17%, respectively, at presynaptic terminals innervating type I or IIa fibers, and by 50 and 36%, respectively, at type IIx and/or IIb fibers (P<0.001, for all comparisons). Thus, matching motoneuron soma and axon terminal inactivity (SH) increases the size and density of releasable synaptic vesicle pools at adult rat diaphragm neuromuscular junctions. Mismatching motoneuron soma and axon terminal inactivities (TTX) results in converse presynaptic adaptations. Inactivity-induced neuromuscular plasticity reflects specific adaptations in the size and density of synaptic vesicle pools that depend on motoneuron soma rather than axon terminal (or muscle fiber) inactivity. PMID- 17346900 TI - Involvement of Na+-Ca2+ exchanger on metabotropic glutamate receptor 1-mediated [Ca2+]i transients in rat cerebellar Purkinje neurons. AB - Cerebellar Purkinje neurons have intracellular regulatory systems including Ca2+ binding proteins, intracellular Ca2+ stores, Ca2+-ATPase and Na+-Ca2+ exchanger (NCX) that keep intracellular Ca2+ concentration ([Ca2+]i) in physiological range. Among these, NCX interacts with AMPA receptors, activation of which induces cerebellar synaptic plasticity. And the activation of metabotropic glutamate receptor 1 (mGluR1) is also involved in the induction of cerebellar long-term depression. The interaction of NCX with mGluR1 is not known yet. Thus, in this study, the functional relationship between NCX and mGluR1 in modulating the [Ca2+]i in rat Purkinje neurons was investigated. The interaction between NCX and mGluR1 in Purkinje neurons was studied by measuring intracellular Ca2+ transients induced by an agonist of group I mGluRs, 3,5-dihydroxyphenylglycine (DHPG). The DHPG-induced Ca2+ transient was significantly reduced by treatments of NCX inhibitors, bepridil and KB-R7943. When cells were pretreated with antisense oligodeoxynucleotides of NCX, the DHPG-induced Ca2+ transient was also inhibited. These results suggest that NCX modulates the activity of mGluR1 in cerebellar Purkinje neurons. Therefore, NCX appears to play an important role in the physiological function of cerebellar Purkinje neurons such as synaptic plasticity. PMID- 17346899 TI - Convergence of stress granules and protein aggregates in hippocampal cornu ammonis 1 at later reperfusion following global brain ischemia. AB - The delayed and selective vulnerability of post-ischemic hippocampal cornu ammonis (CA) 1 pyramidal neurons correlates with a lack of recovery of normal protein synthesis. Recent evidence implicates sequestration of translational machinery into protein aggregates and stress granules as factors underlying persistent translation arrest in CA1 neurons. However, the relationship between protein aggregates and stress granules during brain reperfusion is unknown. Here we investigated the colocalization of protein aggregates and stress granules using immunofluorescence microscopy and pair-wise double labeling for ubiquitin/T cell internal antigen (TIA-1), ubiquitin/small ribosomal subunit protein 6 (S6), and TIA-1/S6. We evaluated the rat dorsal hippocampus at 1, 2 or 3 days of reperfusion following a 10 min global brain ischemic insult. At 1 day of reperfusion, ubiquitin-containing aggregates (ubi-protein clusters) occurred in neurons but did not colocalize with stress granules. At 2 days' reperfusion, only in CA1, cytoplasmic protein aggregates colocalized with stress granules, and ubiquitin-containing inclusions accumulated in the nuclei of CA1 pyramidal neurons. Functionally, a convergence of stress granules and protein aggregates would be expected to sustain translation arrest and inhibit clearance of ubiquitinated proteins, both factors expected to contribute to CA1 pyramidal neuron vulnerability. PMID- 17346901 TI - Antenatal thyroid correlates of postpartum depression. AB - We previously found significantly higher T3-resin uptake and nearly significantly lower total thyroxine concentrations at 38 weeks of pregnancy in women with higher postpartum depression ratings. This study further examined the relationship between thyroid status during late pregnancy and antenatal and postpartum depression scores. Thyroid measures were obtained at 32-35, 36, and 37 weeks of pregnancy in 31 women with normal range thyroid hormone levels. Subjects rated their mood at these antenatal time points and every other week between postpartum weeks 2 and 24 on the Edinburgh Postnatal Depression Scale and the Beck Depression Inventory. Mean antenatal thyroxine concentrations and free thyroxine indices correlated significantly and negatively with mean depression scores during each of three postpartum time periods (postpartum weeks 2-6, 14-18, 20-24). Women with total and free thyroxine concentrations that were, respectively, <10.1 microg/dl and <1.06 ng/dl at all three antenatal time points had significantly higher mean depression scores during all postpartum time periods. The fraction of subjects with pregravid major or minor depression history that was in the low antenatal thyroid group was significantly higher than the fraction of subjects with negative history (5/6 vs. 7/25). Women with antenatal total and free thyroxine concentrations in the lower euthyroid range may be at greater risk of developing postpartum depressive symptoms. Study of the relationships with antenatal thyroid status may provide new insights into the pathophysiology of perinatal mood disturbances. PMID- 17346902 TI - Contractile effect of the aqueous extract of Psidium guajava leaves on aortic rings in rat. AB - Aqueous leaves extract of Psidium guajava significantly and dose-dependently (0.25-2 mg/ml) contracted aorta rings. The effect was evaluated also in presence of nifedipine and phentolamine. The sensitivity of the aortic rings to cumulative doses of P. guajava was significantly enhanced in the presence of phentolamine suggesting that the effect of P. guajava was to a large extent mediated by activation of alpha-adrenoceptor and to a lesser extent by acting via calcium ion channel. PMID- 17346903 TI - In vitro cytotoxic activity of Brazilian plant extracts against human lung, colon and CNS solid cancers and leukemia. AB - The cytotoxicity of extracts obtained from plants occurring in the Amazon and Atlantic rain forests against NCI-H460, KM-12, SF-268 and RPMI-8226 cancer cell lines was investigated. Expressive activity was observed in the extracts of Toulicia cf. pulvinata, Ampirrhox sp., Macoubea sprucei, Calophyllum brasiliense, Vismia guianensis, Caryocar microcarpum, Xylopia aromatica and Distictella magnoliifolia. PMID- 17346904 TI - Seed mucilage from Ipomoea dasysperma. AB - A non-ionic water-soluble galactomannan, having galactose and mannose in 1:6 molar ratio, was isolated from endosperm of the seeds of Ipomoea dasysperma. The seed mucilage was found to have a structure having a linear chain of beta (1-->4) linked mannopyranosyl units with D-galactose side chains attached through alpha (1-->6) linkage to the main chain. I. dasysperma seed gum possesses non-ionic characteristics of commercial seed gums and has potential to be used in food and pharmaceutical industries. PMID- 17346905 TI - Neural-network simulations of two context-dependence phenomena. AB - This paper describes simulations of two context-dependence phenomena in Pavlovian conditioning, using a neural-network model that draws on knowledge from neuroscience and makes no distinction between operant and respondent learning mechanisms. One phenomenon is context specificity or the context-shift effect, the decrease of conditioned responding (CR) when the conditioned stimulus (CS) is tested in a context different from the one in which it had been paired with the unconditioned stimulus (US). The other effect is renewal, the recovery of CR in the training context after extinction in another context. For specificity (simulation 1), two neural networks were first given 200 CS-US pairings in a context. Then, the CS was tested either in the training context or a new context. Output activations in the new context were substantially lower. For renewal (simulation 2), two networks were first given 200 CS-US pairings in a context, then 100 extinction trials in either the same context or a new one, and then tested back in the training context. Output activations during the test phase were substantially higher after extinction in a new context. The results are interpreted in terms of the dynamics of activations and weights. PMID- 17346906 TI - Role of sigmaH paralogs in intracellular melanin formation and spore development in Streptomyces griseus. AB - Streptomyces griseus possesses multiple stress-response sigma factors including sigma(H). Previously, we have suggested that sigma(H) and related sigma factors are involved in the developmental control of S. griseus. Herein, we studied the role of two sigma(H) paralogs--sigma(F) and sigma(N)--which are encoded in tandem coding sequences of sigF-sigN in S. griseus [sigma(N) has been described as sigma(L) previously (Gene 320:127, 2003)]. A sigF mutant produced decreased levels of intracellular melanin and formed irregular spores. A triple mutant for sigHNF exhibited defective melanin production. While sigN was transcribed by three tandem promoters during the early to late growth phases, sigF was transcribed in the late developmental phase by a single promoter. The activity of the promoter preceding the rpp operon (Prpp), which is responsible for the intracellular melanin biosynthesis, was decreased in the sigF mutant and abolished in the sigHNF, adpA and A-factor biosynthesis mutants. The in vitro transcription assay demonstrated that Esigma(F) transcribed the rpp promoter. Both Esigma(F) and Esigma(N) transcribed a sigma(H)-dependent promoter that preceded the sigH operon, and their activities were repressed by the addition of RshA, an anti-sigma(H) protein. Overall, the results suggest that the three sigma factors have similar functions and that they are required for spore development and pigmentation. The transcription of the rpp operon is regulated both by the stress-response sigma factors and the A-factor regulatory cascade. PMID- 17346907 TI - Multiplex real-time PCR for the detection and differentiation of equid herpesvirus 1 (EHV-1) and equid herpesvirus 4 (EHV-4). AB - A multiplex real-time PCR was designed to detect and differentiate equid herpesvirus 1 (EHV-1) and equid herpesvirus 4 (EHV-4). The PCR targets the glycoprotein B gene of EHV-1 and EHV-4. Primers and probes were specific to each equine herpesvirus type and can be used in monoplex or multiplex PCRs, allowing the differentiation of these two closely related members of the Alphaherpesvirinae. The two probes were minor-groove binding probes (MGB) labelled with 6-carboxy-fluorescein (FAM) and VIC for detection of EHV-1 and EHV 4, respectively. Ten EHV-1 isolates, six EHV-1 positive clinical samples, one EHV 1 reference strain (EHV-1.438/77), three EHV-4 positive clinical samples, two EHV 4 isolates and one EHV-4 reference strain (EHV-4 405/76) were included in this study. EHV-1 isolates, clinical samples and the reference strain reacted in the EHV-1 real-time PCR but not in the EHV-4 real-time PCR and similarly EHV-4 clinical samples, isolates and the reference strain were positive in the EHV-4 real-time PCR but not in the EHV-1 real-time PCR. Other herpesviruses, such as EHV-2, EHV-3 and EHV-5 were all negative when tested using the multiplex real time PCR. When bacterial pathogens and opportunistic pathogens were tested in the multiplex real-time PCR they did not react with either system. The multiplex PCR was shown to be sensitive and specific and is a useful tool for detection and differentiation of EHV-1 and EHV-4 in a single reaction. A comprehensive equine herpesvirus disease investigation procedure used in our laboratory is also outlined. This procedure describes the combination of alphaherpesvirus multiplex real-time PCR along with existing gel-based PCRs described by other authors. PMID- 17346908 TI - Monitoring of Usutu virus activity and spread by using dead bird surveillance in Austria, 2003-2005. AB - Usutu virus has been causing avian mortality in Austria since its emergence in 2001. Between 2003 and 2005 a total of 504 dead birds were examined by reverse transcriptase polymerase chain reaction and immunohistochemistry for the presence of Usutu virus nucleic acid and antigen, respectively. In 2003, 92 birds (out of 177 birds) belonging to five different species were positive, while in 2004, only 11 (of 224) birds, and in 2005, 4 (of 103) birds proved positive, all of which were blackbirds (Turdus merula). Within the surveillance period the virus had spread from its initial area of emergence and circulation, the surroundings of Vienna, to large areas of the federal states of Lower Austria, Burgenland and Styria. However, the absolute numbers of Usutu virus associated avian deaths declined significantly during the course of the years. In addition, the proportion of birds with low amounts of virus in their tissues increased continuously, which may indicate developing herd immunity. PMID- 17346909 TI - Effects of a sperminated gelatin on the nasal absorption of insulin. AB - The effects of a sperminated gelatin (SG), which was prepared as a candidate absorption enhancer by the addition of spermine to gelatin, on the nasal absorption of insulin, were examined in rats. The AUC of immuno-reactive insulin levels in the plasma after nasal administration of insulin were increased 5.3 fold by addition of 0.2% SG, and the plasma glucose levels fell in a manner dependent on the insulin levels. In Calu-3 cell monolayer permeation experiments, SG showed significant enhancing effects on 5(6)-carboxyfluorescein (CF), FITC dextran (MW 4400, FD4) and insulin. Evaluation of the tight junctions in the Calu 3 cell monolayers based on the Renkin molecular sieving function suggests that the pore occupancy/length ratio of the permeation pathways for water-soluble molecules in the tight junctions increases, while the equivalent cylindrical pore radius is not changed by SG treatment. SG may transform the true tight junctions, which act as a barrier for water-soluble molecules, into pathways for CF and FD4 to increase their number. SG is a good candidate for a safe absorption enhancer to produce a slight modification of the permeability of the paracellular pathway of mucosal membranes, while retaining the sieving property of the epithelial membranes. PMID- 17346911 TI - Neural coding strategies in auditory cortex. AB - In contrast to the visual system, the auditory system has longer subcortical pathways and more spiking synapses between the peripheral receptors and the cortex. This unique organization reflects the needs of the auditory system to extract behaviorally relevant information from a complex acoustic environment using strategies different from those used by other sensory systems. The neural representations of acoustic information in auditory cortex can be characterized by three types: (1) isomorphic (faithful) representations of acoustic structures; (2) non-isomorphic transformations of acoustic features and (3) transformations from acoustical to perceptual dimensions. The challenge facing auditory neurophysiologists is to understand the nature of the latter two transformations. In this article, I will review recent studies from our laboratory regarding temporal discharge patterns in auditory cortex of awake marmosets and cortical representations of time-varying signals. Findings from these studies show that (1) firing patterns of neurons in auditory cortex are dependent on stimulus optimality and context and (2) the auditory cortex forms internal representations of sounds that are no longer faithful replicas of their acoustic structures. PMID- 17346910 TI - Potassium channel gene expression in the rat cochlear nucleus. AB - Potassium channels play a critical role in defining the electrophysiological properties accounting for the unique response patterns of auditory neurons. Serial analysis of gene expression (SAGE), microarrays, RT-PCR, and real-time RT PCR were used to generate a broad profile of potassium channel expression in the rat cochlear nucleus. This study identified mRNAs for 51 different potassium channel subunits or channel interacting proteins. The relative expression levels of 27 of these transcripts among the AVCN, PVCN, and DCN were determined by real time RT-PCR. Four potassium channel transcripts showed substantial levels of differential expression. Kcnc2 was expressed more than 15-fold higher in the DCN as compared to AVCN and PVCN. In contrast, Kcnj13 had an approximate 10-fold higher expression in AVCN and PVCN than in DCN. Two subunits that modify the activity of other channels were inversely expressed between ventral and dorsal divisions. Kcns1 was over 15-fold higher in DCN than AVCN or PVCN, while Kcns3 was about 25-fold higher in AVCN than in DCN. The expression patterns of potassium channels in the subdivisions of the cochlear nucleus provide a basis for understanding the electrophysiological mechanisms which sub-serve central auditory processing and provide targets for further investigations into neural plastic changes that occur with hearing loss. PMID- 17346912 TI - Population data of nine miniSTR loci in Koreans. AB - For highly degraded DNA samples of forensic casework, new miniSTR systems have been developed to supplement the current STR systems. In the present study, nine miniSTR loci were analyzed in 300 unrelated Koreans using three multiplex PCR systems (multiplex I: D10S1248, D14S1434 and D22S1045; multiplex II: D1S1677, D2S441 and D4S2364; and multiplex III: D3S3053, D6S474 and D20S482), and allele frequencies and forensic parameters were calculated. These data demonstrated that D10S1248, D2S441, D22S1045, D14S1434, and D6S474 are as highly informative as the CODIS STRs suggesting that the miniSTRs could be useful for forensic analysis of degraded DNA. PMID- 17346913 TI - Acromegaly presented as a cause of laryngeal dyspnea. AB - Acromegalic patients can develop obstructive sleep apnea syndrome or upper airflow obstruction. The development of dyspnea is unusual and the fixation of both vocal cords is exceptional. We report the case of a patient with bilateral vocal cord paralysis. Fiberoptic laryngoscopy and computed tomography (CT) of the neck showed a supra-glottic stenosis due to a swelling of the soft tissue. A tracheostomy was first performed. Thereafter, micro-laryngoscopy using laser vaporisation of the supra-glottic soft tissue was attempted but failed to remove the tracheostomy canula. Finally, blood tests and cerebral MRI revealed an acromegaly. The patient underwent a trans-sphenoidal resection of the pituitary adenoma. Fifteen months later, fiberoptic laryngoscopy showed bilateral restoration of vocal cord mobility and the tracheostomy canula was successfully removed after 18 months. Vocal cord fixation is probably due to hypopharyngeal and laryngeal soft tissue swelling and can be reversible after successful treatment of the adenoma. PMID- 17346914 TI - Quantitative analysis of fibrosis and mast cells in the tongue of chronic chagasic patients: autopsy study. AB - OBJECTIVE: Recently, an orally transmitted outbreak of Chagas disease was reported in Santa Catarina, Brazil, after ingestion of sugar cane juice (garapa). This disease is caused by Trypanosoma cruzi, a parasite that stimulates the development of chronic inflammatory response, characterized by fibrous connective tissue neoformation (fibrosis). As the density of tissue mast cells (MC) may be an index of fibroblast proliferation and development of local fibrosis, the purpose of this autopsy study was to quantify the fibrosis rate and the number of MC in the tongues of chronic chagasic (CC) patients, compared with a non-chagasic (NC) control group. METHODOLOGY: Twenty-four evaluations, with a quantitative assessment of fibrosis percentage and MC density were performed. RESULTS: The percentage of fibrosis in the tongue was higher among CC than in the control group. In the CC group, a positive and significant correlation was found when the fibrosis rate was compared with the MC density. CONCLUSIONS: These morphometric findings suggest that tongue biopsy may be useful to study specific changes associated with Chagas disease. They also suggest that the systematic analysis of oral cavity, including tongue histopathology changes, could be useful in forensic pathology of the orally acquired chronic Chagas disease. PMID- 17346915 TI - Impact on adenosine stress cardiac magnetic resonance for recanalisation and follow up of chronic total coronary occlusions. AB - OBJECTIVE: To evaluate the impact on cardiac magnetic resonance imaging (CMRI) with adenosine stress and delayed enhancement for indication and follow up after interventional recanalisation of chronic total coronary occlusions (CTOs). MATERIAL AND METHODS: Twenty consecutive patients (15 males; 5 females; mean age 65 years) with CTO verified by cardiac catheterisation referred to CMRI. Sixteen of them got CMRI before and after coronary recanalisation. Wall motion abnormalities (WMAs), first pass perfusion with adenosine and viability were assessed using a 1.5 T MR scanner (Sonata; Siemens). CMRI results were compared with clinical classifications, the results of cardiac catheterisation and follow up angiography. RESULTS: Sixteen patients had a successful recanalisation, 15 of the occluded coronary artery and one of collateral donor artery stenosis. After recanalisation all stress-induced progressive or new wall motion abnormalities (WMAs) of the corresponding segments and in the collateral donor territory (5 patients) and all adenosine induced perfusion defects (PD) or delay (12 patients) were regredient. 13/16 patients showed no transmural and one patient transmural delayed enhancement (DE) indicating myocardial scar. In 10/16 patients CSS grading of angina improved after recanalisation. CONCLUSION: After successful recanalisation of CTOs, patients with preinterventional stress-induced PDs and WMAs in viable myocardium did not display any signs of stress-induced ischemia postinterventionally. A comprehensive CMRI approach, including assessment of rest and stress WMAs, first pass perfusion and myocardial viability represents an important tool for the pre-interventional decision to recanalise CTOs and follow up. PMID- 17346916 TI - Evaluation of monolithic HPLC columns for various pharmaceutical separations: method transfer from conventional phases and batch to batch repeatability. AB - Methods developed on conventional particle-packed C18 columns for pilocarpine, propranolol, glibenclamide, glimepiride, insulin and their respective degradation products or related compounds were transferred from the conventional Superspher 100RP-18e column to Chromolith Performance RP-18e columns. All transfers were successful applying the same chromatographic conditions, except for insulin where the acetonitrile content of the mobile phase was reduced by 0.5%. The intraday and interday precisions for both retention time and peak area were evaluated over a wide concentration range. Results were found to be equal, or slightly better on Chromolith Performance with RSD%<1.1% in all cases. Monolithic batch to batch repeatability of both retention time and peak area, compared for monolithic columns from different batches gave an RSD% of less than 1.3%. The separation of each drug and its related products was investigated on monolithic columns at flow rates from 1 to 9 ml/min, and superior resolution was always obtained using monolithic over conventional columns at the same flow rate. A total of seven monolithic columns from four different batches were used in this study. PMID- 17346917 TI - Higher preference for participation in treatment decisions is associated with lower medication adherence in asthma patients. AB - OBJECTIVE: To investigate the interrelations between medication adherence, self management, preference for involvement in treatment decisions and preference for information in asthma patients in primary care. METHODS: One hundred and eighty five patients from 43 practices completed a series of questionnaires, which included the 'Autonomy Preference Index' (API) [range=0-100], the four-item Morisky self-report medication adherence questionnaire and structured questions about asthma severity, medication and self-management. RESULTS: The mean (S.D.) for participation preference was 34.5 (15.3) whereas the mean (S.D.) for information preference was 91.1 (9.7). Higher participation preference was associated with stopping medication when feeling better (OR 1.03; 95%CI 1.01 1.06) or feeling worse (OR 1.02; 95%CI 1.0-1.05) but it was not related to asthma severity. Higher information preference was associated with non-adherence to medication (Spearman correlation coefficient 0.166; p=0.035) as well as the wish to receive asthma education (p=0.04) and usage of peak flow meter (p=0.05). CONCLUSION: Participation preference was low in general. Higher preference for involvement may entail more motivation for self-management but also lower medication adherence. This may be explained by a continuous internal negotiation process to accept the potentially lifelong demands of the disease. PRACTICE IMPLICATIONS: Patients with lower medication adherence may possibly be addressed and empowered by their enhanced preference for participation in treatment decisions. Physicians offering to share treatment decisions may utilise the patients' participation preference to enhance medication adherence. Due to varying participation preferences, optimal patient preference matching, which involves more flexible use of different communication styles, may be necessary to improve outcomes. PMID- 17346918 TI - Interest in healthy lifestyle and adherence to medications: Impact on mortality among elderly cardiovascular patients in the DEBATE Study. AB - OBJECTIVE: We examined how a patient-centered consultation can help the physician to evaluate older patients' adherence to medical care and a healthy lifestyle. We hypothesised that an accurate estimate of adherence should be shown in their prognosis. METHODS: Cardiovascular patients (>74 years) in an intervention study (the DEBATE Study) were divided according to physician's clinical impression: (1) "Active adherents" (N=53): those having a healthy lifestyle and adherent to medications. (2) "Passive adherents" (N=65): those not showing any particular interest in a healthy lifestyle but adherent to medications. (3) "Interested scepticals" (N=66): those showing an interest in a healthy lifestyle but feeling sceptical about medications. (4) "Passive non-adherents" (N=15): those having a sedentary lifestyle and non-adherence to medical treatments. The combined endpoint was permanent institutionalisation or death during the average 4.5-year follow-up. RESULTS: Mortality during the 4.5-year follow-up ranged among groups 1 4: 15, 19, 26, and 53% (p=0.01), and the proportions permanently institutionalised 0, 2, 6, and 20% (p=0.003). Multivariate analyses with age, gender, Charlson comorbidity index, dependence in ADL activities and with group 1 as the reference (1.0) showed that both group 3 (HR 2.73, 95% CI 1.11-6.52) and group 4 (HR 6.24, 95% CI 1.88-20.67) were at significantly increased risk for institutionalisation or death. CONCLUSION: In a patient-centered consultation adherence can be accurately evaluated, and such an evaluation is of significant value in the prognosis of older cardiovascular patients. PRACTICE IMPLICATIONS: A patient's expression of attitudes towards medications and healthy lifestyle may be elicited in a patient-centered consultation. This patient-centered approach may help in modifying care to support appropriate, tailored treatments for individual patients. PMID- 17346919 TI - [Anesthetic management of a child with delta sarcoglycanopathy]. AB - A 3-year-old boy of North African decent was seen in the anaesthetic preoperative clinic prior to a scheduled adenoidectomy. His history revealed that his older brother suffered from an unknown form of muscular dystrophy. On clinical exam, no signs of muscular dystrophy were present. However in light of the patient's family history a blood sample for CPK was taken. This was found to be elevated and a neurological consultation was obtained. The patient was diagnosed with a deltasarcoglycanopathy, a rare form of limb girdle muscular dystrophy. A non triggering anaesthetic technique was used, avoiding halogenated anaesthetics and succinylcholine. The preoperative evaluation for a child with a suspected myopathy and the implications for its anaesthetic management are reviewed in this article. PMID- 17346920 TI - [Congenital factor VII deficiency and subarachnoidal haemorrhage due to intracranial aneurysm: a case report]. AB - The management of subarachnoid haemorrhage by aneurysm rupture is well codified. Some rare cases can be problematical. We report a case of a patient suffering from factor VII (FVII) deficiency who presented a subarachnoid haemorrhage by sylvian aneurysm rupture. The bleeding risk was prevented by plasmatic factor VII substitution and aneurysm coiling. Anticoagulation in order to prevent from thromboembolic risk after embolisation was started for 36 hours, associated with plasmatic FVII substitution (with an objective of plasmatic FVII rate of 30%). After this stage at high thromboembolic risk, there has been no shift to platelet antiaggregants and FVII substitution was stopped. The outcome at 1 month was propitious without any bleeding nor arterial thrombosis. PMID- 17346921 TI - [When anaesthetist remove adenoids...]. PMID- 17346923 TI - Glutathione transferases in hepatocyte-like cells derived from human embryonic stem cells. AB - Human embryonic stem cells (hESCs) offer a potential unlimited source for functional human hepatocytes, since hESCs can differentiate into hepatocyte-like cells displaying a characteristic hepatic morphology and expressing several hepatic markers. These hepatocyte-like cells could be used in various human in vitro hepatocyte assays, e.g. as a test system for studying drug metabolism and drug-induced hepatotoxicity. Since the toxic effect of a compound is commonly dependent on biotransformation into metabolites, the presence of drug metabolising enzymes in potential test systems must be evaluated. We have investigated the presence of glutathione transferases (GSTs) in hepatocyte-like cells by immunocytochemistry and Western blotting. Results show that these cells have high levels of GSTA1-1, whereas GSTP1-1 is not present in most cases. GSTM1 1 is detected by immunocytochemistry but not by Western blotting. In addition, GST activity is detected in hepatocyte-like cells at levels comparable to human hepatocytes. These results indicate that the hepatocyte-like cells have characteristics that closely resemble those of human adult hepatocytes. PMID- 17346924 TI - Target identification of drug induced mitochondrial toxicity using immunocapture based OXPHOS activity assays. AB - Mitochondrial dysfunction has been shown to be a pharmacotoxicological response to a variety of currently-marketed drugs. In order to reduce attrition due to mitochondrial toxicity, high throughput-applicable screens are needed for early stage drug discovery. We describe, here, a set of immunocapture based assays to identify compounds that directly inhibit four of the oxidative phosphorylation (OXPHOS) complexes: I, II, IV, and V. Intra- and inter-assay variation were determined and specificity tested by using classical mitochondrial inhibitors. Twenty drugs, some with known mitochondrial toxicity and others with no known mitochondrial liability, were studied. Direct inhibition of one or more of the OXPHOS complexes was identified for many of the drugs. Novel information was obtained for several drugs including ones with previously unknown effects on oxidative phosphorylation. A major advantage of the immunocapture approach is that it can be used throughout drug screening from early compound evaluation to clinical trials. PMID- 17346925 TI - Neurobiology of HIV, psychiatric and substance abuse comorbidity research: workshop report. AB - Viral infections can cause persistent and progressive changes in emotional and cognitive functions. The viral-induced imbalances in neuronal network functioning may precipitate or accentuate psychiatric conditions in vulnerable individuals, in part, as a function of the host response to proinflammatory cytokines resulting from infection or brain injury. Research indicates that the mediators of psychiatric illnesses and HIV-neuropathogenesis utilize similar brain structures, neurocircuitry and receptor systems. The genetic, cellular and molecular mechanisms contributing to HIV neuropathogenesis and its late stage clinical correlate, HIV-associated-dementia (HAD), are active areas of neuroAIDS research. The study of HIV in the context of psychiatric comorbidities and comorbid pathogenesis is in a fledgling stage despite epidemiological studies suggesting that >60% of HIV infected individuals will suffer from at least one major psychiatric disorder during the course of infection. Depression is the primary comorbid disorder but anxiety and substance abuse disorders are also considerable in certain HIV(+) populations. Certain substances of abuse and the biological mediators of psychiatric illnesses reportedly interact in the brain and presumptively worsen HIV-related neuropathogenesis and survival measures. A panel of experts discussed approaches for studying the neuroscience of HIV and psychiatric comorbidity at a basic, mechanistic level since they co-exist in high proportion in the human population. Recommended approaches ranged from improving human consent forms and maximizing the value of repository resources to novel research designs and identifying human and animal endophenotypes. PMID- 17346926 TI - Effects of age, gender, and causality on perceptions of persons with mental retardation. AB - The present study examined the effects of age, gender, and causality on the perceptions of persons with mental retardation. Participants rated individuals with mental retardation using a semantic differential scale with three factors: activity, evaluation, and potency. Target individuals in each scenario varied on the variables of age (8, 20, 45), gender (male, female), and causality of mental retardation (genetic, self-inflicted, inflicted by others). Perceptions differed significantly according to causality, with those with mental retardation due to inheritance/genetics (Down Syndrome) evaluated most positively and those whose mental retardation was self-inflicted viewed most negatively (brain damage due to drinking cleaning fluid). Female participants gave higher ratings than male participants for target subjects on evaluation and potency factors. Implications of findings for persons with mental retardation are discussed. PMID- 17346927 TI - Differential redox regulation within the PTP superfamily. AB - The Protein Tyrosine Phosphatase (PTP) family comprises a large and diverse group of enzymes, regulating a range of biological processes through de-phosphorylation of many proteins and lipids. These enzymes share a catalytic mechanism that requires a reduced and reactive cysteine nucleophile, making them potentially sensitive to inactivation and regulation by oxidation. Analysis of ten PTPs identified substantial differences in the sensitivity of these enzymes to oxidation in vitro. More detailed experiments confirmed the following rank order of sensitivity: PTEN and Sac1>PTPL1/FAP-1>>myotubularins. When the apparent sensitivity to oxidation of these PTPs in cells treated with hydrogen peroxide was analysed, this correlated well with the observed sensitivities to oxidation in vitro. These data suggested that different PTPs may fall into at least three different classes with respect to mechanisms of cellular redox regulation. 1. PTEN and Sac1 were readily and reversibly oxidised in vitro and in cells treated with hydrogen peroxide 2. PTPL1 appeared to be resistant to oxidation in cells, correlating with its sensitivity to reduction by glutathione in vitro 3. The myotubularin family of lipid phosphatases was almost completely resistant to oxidation in vitro and in cells. Our results show that sensitivity to reversible oxidation is not a necessary characteristic of the PTPs and imply that such sensitivity has evolved as a regulatory mechanism for some of this large family, but not others. PMID- 17346928 TI - Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via TRAF6. AB - Interleukin-17F (IL-17F), together with interleukin-17A (IL-17 or IL-17A), is a marker of T(H)17 cells, a new lineage of effector CD4(+) T cells to contribute to pathogenesis of a growing list of autoimmune and inflammatory diseases, such as experimental autoimmune encephalitis (EAE) and collagen-induced arthritis (CIA). IL-17F, similar to IL-17A, was reported to employ interleukin-17 receptor (IL-17R or IL-17RA) for signaling but the downstream cascades remain largely elusive. Here we report that TRAF6 interacts with IL-17R and mediates ubiquitination of the receptor. We observed that IL-17F and IL-17A could induce IL-17R ubiquitination and DN-TRAF6, a dominant-negative mutant, could block IL-17F- but not IL-17A-triggered ubiquitination of IL-17R. Moreover, we showed that the ubiquitination of IL-17R was positively correlated with the downstream signaling, as evaluated by a luciferase reporter driven by a putative native promoter of 24p3, an IL-17 targeted gene. Our results indicate that ubiquitination of IL-17R mediated by TRAF6 plays a critical role in IL-17F signaling. This study, for the first time, reveals a possible molecular mechanism that the initiation of the IL 17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6. PMID- 17346929 TI - The Award for General Nutrition. Best-practice nutrition and dietetic support in Australia. PMID- 17346931 TI - Mental state attribution, neurocognitive functioning, and psychopathology: what predicts poor social competence in schizophrenia best? AB - BACKGROUND: Research into mental state attribution has repeatedly shown that patients with schizophrenia are impaired in their capacity to reflect upon their own and others' beliefs, knowledge and intentions, with important confounds being executive functioning, intelligence, duration of illness, and medication. Furthermore, the extent to which impaired mental state attribution, neurocognition and psychopathology explain abnormal social behavior in schizophrenic patients has been a matter of debate. We sought to determine whether mental state attribution in schizophrenia predicts poor social competence better than "non-social" cognitive factors or psychopathology. METHODS: Intelligence, executive functioning, mental state attribution, psychopathology and social behavior were assessed in 38 patients diagnosed with schizophrenia according to DSM-IV criteria and compared with 29 healthy controls paralleled for age and sex. All patients received antipsychotic treatment, and all participants had no history of substance abuse or traumatic brain injury. RESULTS: In the entire schizophrenia group impaired mental state attribution alone accounted for about 50% of the variance of deviant social behavior, whereas the PANSS positive score and the duration of illness contributed an additional small amount of variance. This effect was even more pronounced in a subgroup of patients with at least normal intelligence, where neither the PANSS score nor the chronicity of the disorder remained significant predictors of poor social competence. Medication was not associated with any one of the neurocognitive measures including mental state attribution, psychopathology or social behavior. CONCLUSIONS: Impaired capacity to appreciate one's own and others' mental states is the single-best predictor of poor social competence in schizophrenia, and should perhaps be included in future definitions of the "core" symptomatology of schizophrenic disorders. PMID- 17346930 TI - Multi-site studies of acoustic startle and prepulse inhibition in humans: initial experience and methodological considerations based on studies by the Consortium on the Genetics of Schizophrenia. AB - BACKGROUND: Startle and its inhibition by weak lead stimuli ("prepulse inhibition": PPI) are studied to understand the neurobiology of information processing in patients and community comparison subjects (CCS). PPI has a strong genetic basis in infrahumans, and there is evidence for its heritability, stability and reliability in humans. PPI has gained increasing use as an endophenotype to identify vulnerability genes for brain disorders, including schizophrenia. Genetic studies now often employ multiple, geographically dispersed test sites to accommodate the need for large and complex study samples. Here, we assessed the feasibility of using PPI in multi-site studies. METHODS: Within a 7-site investigation with multiple measures, the Consortium on the Genetics of Schizophrenia conducted a methodological study of acoustic startle and PPI in CCS. Methods were manualized, videotaped and standardized across sites with intensive in-person training sessions. Equipment was acquired and programmed at the "PPI site" (UCSD), and stringent quality assurance (QA) procedures were used. Testing was completed on 196 CCS over 2.5 years, with 5 primary startle dependent measures: eyeblink startle magnitude, habituation, peak latency, latency facilitation and PPI. RESULTS: Analyses identified significant variability across sites in some but not all primary measures, and determined factors both within the testing process and subject characteristics that influenced a number of test measures. QA procedures also identified non standardized practices with respect to testing methods and procedural "drift", which may be particularly relevant to multi-site studies using these measures. CONCLUSION: With thorough oversight and QA procedures, measures of acoustic startle PPI can be acquired reliably across multiple testing sites. Nonetheless, even among sites with substantial expertise in utilizing psychophysiological measures, multi-site studies using startle and PPI as dependent measures require careful attention to methodological procedures. PMID- 17346932 TI - A clinical study of the association of antipsychotics with hyperlipidemia. AB - Following a prior Kentucky clinical practice study on metabolic syndrome, serum glucose and lipid levels were used in a new sample to determine whether after correcting for confounding factors, olanzapine hyperlipidemia risk may be higher under naturalistic non-randomized treatment. Serum glucose, total cholesterol, HDL cholesterol and triglyceride levels were assessed in 360 patients with severe mental illnesses. The initial goal was to focus on olanzapine lipid profiles, but visual data inspection indicated that quetiapine needed attention as well. Patients were divided into 3 groups: 57 (16%) on olanzapine, 105 (29%) on quetiapine, and 198 (55%) on other antipsychotics (risperidone, ziprasidone, aripiprazole or typicals). HDL and glucose levels were not significantly different across the three antipsychotic groups. When compared with other antipsychotics, olanzapine patients had a borderline significantly higher mean total serum cholesterol level (178 vs. 192 mg/dl, p=0.06) and mean triglyceride level (172 vs. 202 mg/dl, p=0.06). These differences became significant (p=0.006 and 0.03) after correcting for confounders. Quetiapine appeared overprescribed in patients with metabolic syndrome complications. When compared with other antipsychotics, quetiapine patients had a significantly higher mean total serum cholesterol level (178 vs. 194 mg/dl, p=0.004) and mean triglyceride level (172 vs. 225 mg/dl, p<0.001). These differences were significant (p=0.02 and <0.001) after correcting for confounders. This study is consistent with emerging literature that suggests that some antipsychotics may have direct and immediate effects on lipid levels beyond obesity effects. The effect sizes of olanzapine and quetiapine on hyperlipidemia were about 0.40 in this naturalistic study. PMID- 17346933 TI - Subclinical psychotic experiences and cognitive functioning as a bivariate phenotype for genetic studies in the general population. AB - OBJECTIVE: Cognitive deficits may be vulnerability markers for the development of schizophrenia. This study examined whether cognitive deficits are related to specific dimensions of subclinical psychotic experiences and whether associations between these variables are caused by additive genetic, common environmental and/or individual-specific environmental factors. METHOD: A general population sample of 298 female twin pairs completed the Community Assessment of Psychic Experiences and a neuropsychological test battery. Associations between subclinical positive and negative psychotic dimensions and neuropsychological factors (episodic memory and information processing speed) were examined. Univariate correlation and structural equation analyses were performed to explore the role of genetic and environmental factors in the phenotypes separately. Bivariate correlation and structural equation analyses were applied to examine the causes of association. RESULTS: There were significant correlations between information processing speed and both the positive (r=.11; p<.05) and the negative dimension (r=.10; p<.05). For the negative dimension and for speed of processing, the data suggested a model that included genetic factors. The observed phenotypic correlation between the negative dimension and information processing speed could be solely explained in terms of additive genetic factors. Although the comparison of the correlations for MZ and DZ pairs did not give a clear indication as to the underlying causes of the association, structural equation modelling suggested that the observed phenotypic correlation between the negative dimension and information processing speed could be solely explained in terms of additive genetic factors. CONCLUSION: Negative symptoms and information processing speed are associated at the subclinical level and this association appears to be influenced by genetic factors exclusively. Bivariate psychosis phenotypes may represent suitable candidates for molecular genetic studies in the general population. PMID- 17346934 TI - Increase of collagen synthesis by obovatol through stimulation of the TGF-beta signaling and inhibition of matrix metalloproteinase in UVB-irradiated human fibroblast. AB - BACKGROUND: Alterations of the extracellular matrix (ECM) is critical in the photo and age-damaged skin. Thus any compounds keep ECM can protected from photo and aged-damaged skin. ECM is predominantly composed of type I and type III collagens in the dermis. Transforming growth factor (TGF-beta)s play important roles in cellular biosynthesis of extracellular matrix. Activator protein 1 (AP 1) and Smad are significant factors that mediate TGF-beta. OBJECTIVE: We have investigated increasing effects of obovatol, a biphenolic compound isolated from leaves of Magnolia obovata on the collagen synthesis through stimulation of the TGF-beta signaling and inhibition of matrix metalloproteinase, thereby protect against from UV damages via maintain of collagen in the UVB irradiated human fibroblast cells. METHODS: The fibroblasts were pretreated with obovatol for 24h and then the cells were irradiated with UVB. UVB-exposed cells were further cultured for 24h. Type I procollagen, MMP-3, TGF-beta and Smad as well as phosphorylation of MAPK family expression were determined by Western blot. The activation of AP-1 was investigated using EMSA. The released type I procollagen and TGF-beta into cell culture medium were determined by Western blot after concentration of these proteins. RESULTS: The results showed that obovatol stimulated type I procollagen, TGF-beta, and Smad expression and inhibited matrix metalloproteinase-3 (MMP-3) in dose-dependent manner (1-5muM) in UVB-irradiated human fibroblast cells. Obovatol also inhibited UVB-induced activation of AP-1 and MAP kinases. CONCLUSION: These results suggest that obovatol increases collagen synthesis through stimulation of the TGF-beta signaling and inhibition of matrix metalloproteinase in UVB-irradiated human fibroblast, thus obovatol could be effective against photo-damaged skin. PMID- 17346935 TI - Evolution of mitochondrial SSU-rDNA variable domain sequences and rRNA secondary structures, and phylogeny of the Agrocybe aegerita multispecies complex. AB - Mitochondrial small subunit (mtSSU) rDNA variable (V1, V2, V4, V6, V8 and V9) domain sequences and rRNA secondary structures evidenced eight molecular groups within 32 strains of the Agrocybe aegerita multispecies complex from different continents. mtSSU-rRNA secondary structure evolution occurred mainly by insertion/deletion of sequences from 8 to 57nt long. Preferential insertion/deletion sites correlated with loops of the mtSSU-rRNA secondary structures, and suggested that these events occurred in regions without interactions in the ribosomal-protein assembly. Indels modified the stem length (V1 and V4 domains) or the size and loop number (V6 and V9 domains). Three indels inserted in the V1 and V4 domains had 76.5% to 94.7% identity with short sequences of the mitochondrial cytochrome c oxidase gene; this fact and the presence of inverted repeated motifs within indel sequences suggested a mechanism of evolution based on insertion/deletion of sequences from another region of the mitochondrial genome. Phylogenetic relationships inferred using both ribosomal DNA sequences and rRNA secondary structures were congruent and evidenced three clades within the A. aegerita complex: European, Argentinean, and a more distant Asian-American clade including A. aegerita and A. chaxingu strains. These results suggested that numerous genetic exchanges occurred between Asian-American strains after isolation of the European clade. V4-V6-V9 concatenated sequences of European and Argentinean clades had 86.1% identity, similar to the value calculated between two Agrocybe closely related species, suggesting that these clades could represent different species. A cleaved amplified polymorphic sequence test for rapid characterization of strains was developed. PMID- 17346936 TI - Genetic diversity of the HpyC1I restriction modification system in Helicobacter pylori. AB - Helicobacter pylori is unique because of the unusually high number and diversity of its restriction modification (R-M) systems. HpyC1I R-M was recently characterized and contains an endonuclease which is an isoschizomer of the endonuclease BccI. This R-M is involved in adherence to gastric epithelial cells, a crucial step in bacterial pathogenesis. This observation illustrates the fact that R-M systems have other putative biological functions in addition to protecting the bacterial genome from external DNA. The genomic diversity of HpyC1I R-M was evaluated more precisely on a large collection of H. pylori strains by PCR, susceptibility to BccI digestion and sequencing. The results obtained support the mechanism of gain and loss of this R-M system in the H. pylori genome, and suggest that it is an ancestral system which gradually disappears during H. pylori evolution, following successive steps: (1) inactivation of the endonuclease gene, followed or accompanied by: (2) inactivation of the methyltransferase genes, and then: (3) definitive loss, leaving only short endonuclease remnant sequences. PMID- 17346937 TI - Archaeal and bacterial community composition of sediment and plankton from a suboxic freshwater pond. AB - We studied the composition of archaeal and bacterial communities present in the sediment and plankton of a shallow suboxic-to-anoxic freshwater pond with high organic matter input, as an example of a kind of inland freshwater system widely distributed in forests of temperate regions. Molecular surveys based on small subunit rRNA genes showed a remarkably high diversity of lineages within the Bacteria, with a total of 18 phyla or candidate divisions being detected, in addition to a few highly divergent phylotypes of unknown affiliation. We identified members of the five subdivisions of the Proteobacteria, as well as Acidobacteria, Verrucomicrobia, Planctomycetes, Bacteroidetes, Chlorobi, Actinobacteria, Firmicutes, Chloroflexi, Gemmatimonadetes, Spirochaetes, Fibrobacteres and the candidate divisions OD1, OP11, TM6, WS1, WS6 and Termite Group 1 ("Endobacteria"). Candidate division OD1 and beta-Proteobacteria were dominant in the environmental libraries of plankton and sediment, respectively. Archaea were also very diverse, but only members of the Euryarchaeota, including Methanosarcinales, Methanomicrobiales and some divergent lineages, were identified. The application of various species richness estimators confirmed the highly diverse nature of both plankton and sediment samples. The pond is a microbial-based complex ecosystem mainly fueled by the degradation of allochthonous organic matter that maintains tightly coupled carbon and sulfur cycles. PMID- 17346938 TI - Antimicrobial treatment for Intensive Care Unit (ICU) infections including the role of the infectious disease specialist. AB - Between 5 and 10% of patients admitted to acute care hospitals acquire one or more infections, and the risks have steadily increased during recent decades. Three types of infection account for more than 60% of all nosocomial infections: pneumonia, urinary tract infection and primary bloodstream infection, all of them associated with the use of medical devices. Nearly 70% of infections are due to micro-organisms resistant to one or more antibiotics (multidrug resistant or MDR). A higher incidence of inappropriate antibiotic therapy is expected when infections are caused by antibiotic-resistant micro-organisms and initial inappropriate empirical therapies, and the further need to modify them substantially increases the mortality risk. Despite new antibacterial agents such as linezolid, and also tigecycline and daptomycin, now being available for the treatment of infections due to MDR micro-organisms, the best strategy for improving the cure rate and minimising the development of resistance, probably remains the infectious disease specialist consultation. PMID- 17346939 TI - Empirical antimicrobial treatment for chemotherapy-induced febrile neutropenia. AB - Febrile neutropenia in immunocompromised hosts is associated with a high mortality. Empirical treatment in such cases is instituted to cover the common pathogens. Generally, combination antibiotic treatment is used early in the febrile neutropenia phase. Recent studies demonstrate that monotherapy with certain beta-lactam antibiotics can be equally effective. Glycopeptide antibiotics are used in the absence of an adequate response to the initial antibiotics. Empirical antifungal therapy may be given if fever does not settle in 72-96 h despite antibiotics. Newer antifungal agents have increased the available options for initial antifungal agents though more data are needed before any conclusive recommendation can be made. Recent changes in the epidemiology of multiresistant organisms necessitate local microbiological input into empiric policies with increasing need to consider cover for methicillin resistant Staphylococcus aureus, glycopeptide intermediate S. aureus, vancomycin resistant S. aureus, vancomycin-resistant enterococci, Gram-negative bacilli that produce extended-spectrum beta-lactamases, Stenotrophomonas maltophilia, and multi-resistant Acinetobacter baumanii. PMID- 17346940 TI - HIV resistance and the developing world. AB - Rollout of antiretroviral therapy (ART) in resource-limited countries has been identified as a global public health priority. Human immunodeficiency virus (HIV) treatment in the industrialised world is routinely accompanied by regular virological monitoring. By contrast, the implementation of ART in resource limited settings requires use of standard first- and second-line therapy. One major consequence is the likely emergence of high-level resistance during first line therapy since most people will stay on a virologically failing regimen for longer periods, potentially compromising the efficacy of second-line therapy. The evidence regarding resistance to triple-drug ART relates to the time at which virological failure occurs in populations from developed countries, with little data from resource-poor contexts where monitoring strategies, HIV subtypes and drug combinations are likely to differ. PMID- 17346941 TI - Screening social phobia in adolescents from general population: the validity of the Social Phobia Inventory (SPIN) against a clinical interview. AB - Social phobia (SP) has onset during early adolescence, and is associated with significant impairment in social and educational functioning of adolescents. Therefore, valid and easy-to-use tools for screening and identification of SP among adolescent community populations are needed. We investigated both construct and discriminative validity, and screening properties of the 17-item Social Phobia Inventory (SPIN) relative to SP diagnoses based on a semi-structured clinical interview (K-SADS-PL), in a sample of 752 12 to 17-year-old Finnish students from general population. The SPIN demonstrated good properties to differentiate adolescents with SP and those with sub-clinical SP symptoms (SSP), from adolescents without SP. The SPIN also differentiated adolescents with SP from those with depressive and disruptive disorders. In this sample 27% of participants scored above the previously suggested SPIN cut-off (15 points) for adolescent SP. We suggest using a somewhat higher cut-off score, 24 points, when using the SPIN as a screen for SP in general adolescent populations. This cut-off score resulted in a sensitivity of 81.2%, a specificity of 85.1%, a positive predictive value of 26.9%, and a negative predictive value of 98.6% in relation to the SP diagnosis in our sample. To screen for both SP and SSP, 19 points as a cut-off score produced satisfactory diagnostic efficiency statistics. The SPIN appears to have good properties for screening and identification of adolescent SP. PMID- 17346942 TI - A study of the discriminative validity of a screening tool (MINI-SPIN) for social anxiety disorder applied to Brazilian university students. AB - OBJECTIVE: This study aimed to evaluate the discriminative validity of MINI-SPIN (MS) as a screening tool for social anxiety disorder (SAD) in a group of Brazilian university students. METHOD: SPIN was collectively applied to 2320 university students. Among them, 656 individuals who fulfilled the criteria for positive MS (N=473) and negative MS (N=183) were selected and divided into two groups. The selected subjects were interviewed by telephone using the SAD module of the SCID-IV, used as the gold standard. In order to check interrater reliability, a group of university students (N=57) was reinterviewed by telephone by a second rater, and another group (N=100) participated in a face-to-face interview. RESULTS: The Kappa coefficient among the telephone interviews was 0.80, and a coefficient of 0.84 (P<0.001) was obtained between the telephone interview and the face-to-face one. For a cut-off score of 6, suggested in the original English version of the instrument, sensitivity was 0.94, specificity 0.46, the positive predictive value (PPV) was 0.58, and the negative predictive value (NPV) was 0.92. For a cut-off score of 7, we observed an increase in the specificity and in the PPV (0.68 and 0.65) while the sensitivity and NPV (0.78 and 0.80) remained high. DISCUSSION/CONCLUSION: MS showed quite satisfactory psychometric qualities. The cut-off score of 6 seemed to be the most suitable to attest the tracking value of the tool. However, the cut-off score of 7 was the most suitable as a minimum parameter for the studied group, with psychometric values more similar to those of the original study. PMID- 17346943 TI - Reduced orexin levels in the cerebrospinal fluid of suicidal patients with major depressive disorder. AB - Orexins are neuropeptides selectively expressed in a small number of neurons in the lateral-posterior hypothalamus. We measured orexin-A in the cerebrospinal fluid (CSF) of 66 patients with major depressive disorder (MDD), dysthymia and adjustment disorder after a suicide attempt. Blood samples confirmed that the patients were free from antidepressive and neuroleptic medication at the time of the lumbar punctures. CSF levels of orexin-A were significantly lower in patients with MDD than in patients with adjustment disorder and dysthymia. Orexin correlated significantly with CSF levels of somatostatin, delta sleep inducing peptide-like immunoreactivity (DSIP-LI) and corticotrophin releasing factor (CRF), but not with leptin or vasopressin. Plasma levels of thyroid-stimulating hormone (TSH) were not reduced in MDD patients, and did not correlate with CSF orexin. Our results suggest that suicidal patients with MDD have distinct neurobiological features, involving compromised levels of hypothalamic peptides regulating the state of arousal. PMID- 17346944 TI - Circulatory neurosteroid levels in smoking and non-smoking chronic schizophrenia patients. AB - INTRODUCTION: Schizophrenia patients display an extremely high rate of smoking. Neurosteroids appear to play a possible role in the pathophysiology and management of schizophrenia and have been proposed to be involved in the pathophysiology of nicotine addiction. Although many studies have evaluated blood levels of neurosteroids in schizophrenia patients, only a few studies have taken into consideration the effect of smoking on levels of neurosteroids in the illness. METHODS: Forty-five DSM-IV-TR chronic schizophrenia patients were sampled for plasma levels of three steroids: cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA-S). Patients were rated with the Positive and Negative Syndrome Scale (PANSS) and provided data on their smoking behavior. RESULTS: The mean level of plasma cortisol in our sample (N=45) was 197.9 nmol/L (S.D.=81.5), and the levels of DHEA and DHEA-S were 23 nmol/L (S.D.=5.5) and 4276.6 nmol/L (S.D.=2665.58), respectively. Despite a trend for lower levels of cortisol, DHEA and DHEA-S among the smokers, only DHEA, but not DHEA-S and cortisol, was significantly lower among the smokers (33% decrease, p=0.012). Smoking predicted the positive and negative scores of the PANSS, whereas cortisol was correlated with the PANSS-negative subscale. CONCLUSIONS: Smoking in chronic schizophrenia patients appears to be associated with lower DHEA levels. The role of this decrease in the pathophysiology of nicotine addiction and schizophrenia merits further investigation. PMID- 17346945 TI - Role of TRPV receptors in respiratory diseases. AB - Transient receptor potential vanilloid type channels (TRPVs) are expressed in several cell types in human and animal lungs. Increasing evidence has demonstrated important roles of these cation channels, particularly TRPV1 and TRPV4, in the regulation of airway function. These TRPVs can be activated by a number of endogenous substances (hydrogen ion, certain lipoxygenase products, etc.) and changes in physiological conditions (e.g., temperature, osmolarity, etc.). Activation of these channels can evoke Ca(2+) influx and excitation of the neuron. TRPV1 channels are generally expressed in non-myelinated afferents innervating the airways and lungs, which also contain sensory neuropeptides such as tachykinins. Upon stimulation, these sensory nerves elicit centrally-mediated reflex responses as well as local release of tachykinins, and result in cough, airway irritation, reflex bronchoconstriction and neurogenic inflammation in the airways. Recent studies clearly demonstrated that the excitability of TRPV1 channels is up-regulated by certain autacoids (e.g., prostaglandin E(2), bradykinin) released during airway inflammatory reaction. Under these conditions, the TRPV1 can be activated by a slight increase in airway temperature or tissue acidity. Indirect evidence also suggests that TRPV channels may play a part in the pathogenesis of certain respiratory diseases such as asthma and chronic cough. Therefore, the potential use of TRPV antagonists as a novel therapy for these diseases certainly merits further investigation. PMID- 17346946 TI - HIV envelope protein gp120-triggered CD4+ T-cell adhesion to vascular endothelium is regulated via CD4 and CXCR4 receptors. AB - Activation of T-lymphocytes is an important component of inflammatory and infectious processes, including HIV infection. It is regulated via the actions of various cell-surface receptors, including CD4 and CXCR4. We examined the roles of CD4 and CXCR4 in the adhesive interaction of CD4+T-cells with the vascular endothelium. CD4+Jurkat cells were incubated in the presence or absence of anti CD4 to stimulate CD4, or with SDF-1 alpha, a cognate ligand of CXCR4. Stimulation of CD4 or CXCR4 each significantly enhanced cell adhesion. We next stimulated the two receptors together, using gp120, a component of HIV. This enhanced cell adhesion was greater than stimulation of CD4 or CXCR4 individually. Western blotting revealed that stimulation of CXCR4 by SDF-1 alpha significantly increased the phosphorylation of ERK1/2 in Jurkat cells. Treatment with anti-CD4 also activated ERK1/2, although to a lesser extent. When the expression of CD4 was reduced by siRNA transfection, both CD4-dependent adhesion and MAPK activation were diminished. Furthermore, pre-treatment with fluvastatin, significantly attenuated observed Jurkat cell adhesion. These findings indicate novel mechanisms of CD4+ T-cells recruitment to activated endothelium via CD4 and CXCR4, which are modulated by statin. PMID- 17346947 TI - TRP channels in kidney disease. AB - Mammalian TRP channel proteins form six-transmembrane cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Recent studies of TRP channels indicate that they are involved in numerous fundamental cell functions and are considered to play an important role in the pathophysiology of many diseases. Many TRPs are expressed in kidney along different parts of the nephron and growing evidence suggest that these channels are involved in hereditary, as well as acquired kidney disorders. TRPC6, TRPM6, and TRPP2 have been implicated in hereditary focal segmental glomerulosclerosis (FSGS), hypomagnesemia with secondary hypocalcemia (HSH), and polycystic kidney disease (PKD), respectively. In addition, the highly Ca(2+)-selective channel, TRPV5, contributes to several acquired mineral (dys)regulation, such as diabetes mellitus (DM), acid-base disorders, diuretics, immunosuppressant agents, and vitamin D analogues associated Ca(2+) imbalance whereas TRPV4 may function as an osmoreceptor in kidney and participate in the regulation of sodium and water balance. This review presents an overview of the current knowledge concerning the distribution of TRP channels in kidney and their possible roles in renal physiology and kidney diseases. PMID- 17346948 TI - In vivo metabolite differences between the basal ganglia and cerebellum of the rat brain detected with proton MRS at 3T. AB - In vivo magnetic resonance spectroscopy (MRS) enables non-invasive longitudinal tracking of brain chemistry changes that can accompany aging, neurodegenerative disease, drug addiction and experimental manipulations in animals modeling such conditions. J-coupled resonances, such as glutamate, which are highly relevant to neuropsychiatric conditions are difficult to resolve on a clinical 3T MR scanner using conventional one-dimensional MRS sequences. We, therefore, implemented Constant Time PRESS (CT-PRESS) to quantify major metabolite and neurotransmitter biochemical signals, including glutamate, in two brain regions of the rat, basal ganglia and cerebellum. We acquired spectra at two distinct time points in two independent groups of six rats and analyzed metabolite levels using either creatine or water as a reference. Our results provide evidence that CT-PRESS at 3T is adequate and reliable for in vivo detection and quantification of glutamate in the rat brain and that regional differences occur in the signal intensities of the major metabolites. That the directionality of the differences depends on whether creatine or water is used as a reference for metabolite levels emphasizes the benefit to in vivo MRS of incorporating methods to establish absolute baseline metabolite concentrations. PMID- 17346949 TI - Reduced concentrations of N-acetylaspartate (NAA) and the NAA-creatine ratio in the basal ganglia in bipolar disorder: a study using 3-Tesla proton magnetic resonance spectroscopy. AB - The N-acetylaspartate (NAA) peak is prominent in the proton magnetic resonance spectrum and is thought to reflect neuron loss or dysfunction. This study was conducted to explore NAA biochemistry and its clinical correlates in mania. Subjects comprised 16 manic patients and 17 controls who underwent a structured diagnostic interview and (1)H magnetic resonance spectroscopy (MRS) acquisition. STEAM (1)H MRS (TR/TE/TM=2000/20/8 ms) was acquired at 3 Tesla from 2 x 2 x 2 cm(3) voxels in anterior cingulate (AC), right basal ganglia (BG), and left occipital-parietal white matter (OP). Absolute metabolite concentrations and ratios to creatine were calculated using the LC Model. The mean absolute concentrations of NAA and NAA-creatine ratio in the BG were significantly lower in manic subjects than in controls. There was a significant inverse correlation between NAA in the BG and the number of prior hospitalizations for mania. These data suggest BG pathology in mania and that NAA decrements may mark prior manic episode burden. Limitations of this study include small sample size and lack of tissue segmentation. Further study is encouraged to clarify state vs. trait aspects of NAA in bipolar disorder. PMID- 17346950 TI - [Focusing of inguinal hernia in children]. AB - Abnormal persistence of the processus vaginalis in children predisposes to a complication that is strangulated inguinal hernia. The inguinal hernia is a frequent pathology because global incidence varies from 0,8 to 4,4% for children of any age and reaches about 30% in premature children. Strangulated inguinal hernia is rare (from 1,5 to 8%) and constitutes a surgical emergency. More frequently, reduction following sedation is possible (from 25 to 33%), and normally leads to delayed surgery. Current practice is to operate early in these children, including preterm infants, before any complication arises. This early surgery requires use of regional anaesthetic techniques such as spinal anaesthesia, ileo-inguinal ileohypogastric nerve blocks and caudal anaesthesia. However, although this pathology may appear to be routine commonplace it requires a specialized surgical and anaesthetic approach and specialized environment. PMID- 17346951 TI - The effects of polyphenols in olive leaves on platelet function. AB - INTRODUCTION: The phenolic compounds of olive leaves and olive oils in the Mediterranean diet have been associated with a reduced incidence of heart disease. Accordingly, antioxidant-rich diets may prevent the deleterious effects of oxidative metabolism by scavenging free radicals, thus inhibiting oxidation and delaying atherosclerosis. The process involves phospholipase C activation and arachidonic acid metabolism, and is thought to reduce hydrogen peroxide (H(2)O(2)). In our study, an extract of Olea europaea L. leaves was used. The active phenolic compounds in this extract are part of the secoiridoid family, known for their capacity to scavenge H(2)O(2). The results from this study will help to improve our understanding of effects of polyphenol antioxidants in olive leaf extract on platelet function. METHODS: Full blood examination (FBE), platelet aggregation, and ATP release were performed on samples from fasting, normal, healthy male subjects. Platelet function at increasing concentrations of oleuropein was investigated through measures of platelet aggregation and ATP release from activated platelets. RESULTS: Blood analysis (n=11) revealed a significant dose-dependant reduction in platelet activity with olive extract concentrations of 1.0% v/v (P<0.001). ATP Release showed a similar pattern (P=0.02). CONCLUSIONS: Olive leaf polyphenols derived from O. europaea L. leaves inhibited in vitro platelet activation in healthy, non-smoking males. Further bioavailability studies need to be undertaken to determine the in vivo effect of extract on platelet function and to validate the present results. PMID- 17346952 TI - QT-interval dispersion in type 2 diabetic and non-diabetic patients with post myocardial infarction. AB - BACKGROUND AND AIMS: QT-interval dispersion (QTD), which reflects spatial ventricular repolarization inhomogeneity, has been reported to increase and to have a prognostic value in patients with either myocardial infarction or diabetes. Our aim was to compare increases in QTD in type 2 diabetic and non diabetic patients following post-myocardial infarction (post-MI). We also compared QTD in type 2 diabetic patients with post-MI treated with insulin, sulfonylurea, or diet alone. METHODS AND RESULTS: We determined the rate corrected QT-interval (QTc) dispersion (QTcD) in 178 consecutive post-MI patients, including 48 type 2 diabetic and 130 non-diabetic patients. The QTcD, measured with software (QTD-1), was defined as the difference in the minimum and maximum QTc in any of the 12 standard electrocardiographic leads. There were no significant differences in age, gender, left ventricular end-diastolic diameter, ejection fraction, or minimum QTc between type 2 diabetic and non-diabetic patients with post-MI. Compared with post-MI patients without diabetes, those with type 2 diabetes had higher maximum QTc (481+/-37 vs. 459+/-43ms, P<0.05) and QTcD (67+/-18 vs. 58+/-16ms, P<0.05). Among type 2 diabetic patients with post-MI treated with insulin, sulfonylurea, or diet alone, the QTcD (81+/-18 vs. 64+/-16 vs. 62+/-17ms, P<0.05, respectively) was significantly greater and the R-R interval was shorter in the insulin therapy group. CONCLUSIONS: Type 2 diabetes is associated with an additional increase in the QTD in post-MI patients. This additional increase in spatial repolarization inhomogeneity might be implicated in the increased mortality risk in post-MI patients with type 2 diabetes. These findings were thought to be more striking in the insulin therapy group. PMID- 17346953 TI - Cetyl palmitate-based NLC for topical delivery of Coenzyme Q(10) - development, physicochemical characterization and in vitro release studies. AB - In the present study, nanostructured lipid carriers (NLC) composed of cetyl palmitate with various amounts of caprylic/capric triacylglycerols (as liquid lipid) were prepared and Coenzyme Q(10) (Q(10)) has been incorporated in such carriers due to its high lipophilic character. A nanoemulsion composed solely of liquid lipid was prepared for comparison studies. By photon correlation spectroscopy a mean particle size in the range of 180-240nm with a narrow polydispersity index (PI) lower than 0.2 was obtained for all developed formulations. The entrapment efficiency was 100% in all cases. The increase of oil loading did not affect the mean particle size of NLC formulations. NLC and nanoemulsion, stabilized by the same emulsifier, showed zeta potential values in the range -40/-50mV providing a good physical stability of the formulations. Scanning electron microscopy studies revealed NLC of disc-like shape. With respect to lipid polymorphism, a decrease in the ordered structure of NLC was observed with the increase of both oil and Q(10) loadings, allowing therefore high accommodation for Q(10) within the NLC. Using static Franz diffusion cells, the in vitro release studies demonstrated that Q(10)-loaded NLC possessed a biphasic release pattern, in comparison to Q(10)-loaded nanoemulsions comprising similar composition of which a nearly constant release was observed. The NLC release patterns were defined by an initial fast release in comparison to the release of NE followed by a prolonged release, which was dependent on the oil content. PMID- 17346954 TI - Preparation and characterization of free mixed-film of pectin/chitosan/Eudragit RS intended for sigmoidal drug delivery. AB - Polyelectrolyte complex (PEC) film between pectin as an anionic polyelectrolyte and chitosan as a cationic species was prepared by blending two polymer solutions at weight ratio of 2:1 and then solvent casting method. Besides pectin/chitosan PEC film, Eudragit RS, pectin/Eudragit RS and pectin/chitosan/Eudragit RS films were also prepared by aforementioned method. In mixed-film formulations, a fixed weight ratio of 1:5 of pectin or pectin/chitosan complex to Eudragit RS was used. Characterizations of pectin/chitosan interaction in solution were investigated by turbidity and viscosity measurement and in the solid state by Fourier transform infrared (FTIR) spectroscopy, wide angle X-ray diffraction (WAXRD) and thermogravimetric analysis (TGA). It was observed that the swelling profile of pectin/chitosan film was pH-dependent and its swelling ratio in phosphate buffer solution (PBS) pH 7.4 was about 2.5-fold higher than that of PBS pH 6.0. Formulation containing only pectin/chitosan could not protect free film from high swelling in the aqueous media, therefore, Eudragit RS as a water-insoluble polymer must be included in the mixed-film. The formation of PEC between pectin and chitosan resulted in a decrease in the crystallinity and thermal stability caused by the interactions between polyions. Drug permeation or diffusion studies were carried out using Plexiglas diffusion cell consisting of donor and acceptor compartments. Theophylline was selected as a model drug to measure permeability coefficient. Drug permeation through pectin/chitosan/Eudragit RS showed a sigmoidal pattern; whereas drug diffusion through pectin/Eudragit RS and Eudragit RS films followed a linear characteristic. The drug permeation through the ternary mixed-film showed a burst release upon exposure to PBS pH 6.0. This mixed film formulation showed the potential for sigmoidal drug delivery with an initial, controllable slow release followed by a burst release immediately after the change in pH. The burst drug permeation might possibly be due to change in film's porosity. PMID- 17346955 TI - Acetylcholinesterase inhibitors from plants. AB - Inhibition of acetylcholinesterase (AChE), the key enzyme in the breakdown of acetylcholine, is considered as a promising strategy for the treatment of neurological disorders such as Alzheimer's disease, senile dementia, ataxia and myasthenia gravis. A potential source of AChE inhibitors is certainly provided by the abundance of plants in nature. This article aims to provide a comprehensive literature survey of plants that have been tested for AChE inhibitory activity. Numerous phytoconstituents and promising plant species as AChE inhibitors are being reported in this communication. PMID- 17346956 TI - Glutamate-induced cell death in neuronal HT22 cells is attenuated by extracts from St. John's wort (Hypericum perforatum L.). AB - Glutamate-induced cell death of hippocampal HT22 cells is a model system for neuronal disorders due to depletion of glutathione levels and increase of intracellular reactive oxygen species. Standardized extracts of Hypericum perforatum (HPE) contain flavonoids known for antioxidative properties. In the above model, cytoprotective effects at a concentration of 0.05% HPE by attenuation of calcium fluxes and cellular energy statuses are reported. PMID- 17346957 TI - Correlates of non-thyroidal illness syndrome in chronic obstructive pulmonary disease. AB - Non-thyroidal illness syndrome (NTIS) is frequently detected in chronic, systemic diseases. The objectives of the current study is to assess the alterations of thyroid hormones during exacerbation period, recovery of exacerbation and stable phase of chronic obstructive pulmonary disease (COPD) and correlates of these hormonal alterations. A total of 83 stable COPD patients, 20 patients with acute exacerbation and 30 control subjects were evaluated. TT3, fT3, TT3/TT4 levels of both stable and exacerbation COPD groups were lower than control subjects. TSH was also decreased during exacerbation period. In follow-up of COPD exacerbation group, TSH, TT3, fT3 and TT3/TT4 were found to be increased in measurements on the day of discharge from hospital and after 1 month, compared to baseline values. TT3 and TT3/TT4 were lower in severe COPD; whereas TSH, fT3, TT3 and TT3/TT4 were lower in patients with severe hypoxemia. IL-6 and TNF-alpha were higher in both stable and exacerbation phase COPD groups and IL-6 was correlated to TT3 in stable COPD. As a result, there are significant alterations in thyroid hormones of stable COPD patients, which are related to severity of disease and hypoxemia. The hormonal changes are more significant during exacerbation and partially regress after 1 month when the disease is stabilized. We conclude that COPD patients should not be evaluated for thyroid disease during exacerbation of the disease, and thyroid function alterations during stable phase of the disease should be considered cautiously, since thyroid function abnormalities in non thyroid illness may mimic or mask biochemical abnormalities observed in true thyroid disease. PMID- 17346958 TI - Investigation of MSWI fly ash melting characteristic by DSC-DTA. AB - The melting process of MSWI (Municipal Solid Waste Incineration) fly ash has been studied by high-temperature DSC-DTA experiments. The experiments were performed at a temperature range of 20-1450 degrees C, and the considerable variables included atmosphere (O(2) and N(2)), heating rates (5 degrees C/min, 10 degrees C/min, 20 degrees C/min) and CaO addition. Three main transitions were observed during the melting process of fly ash: dehydration, polymorphic transition and fusion, occurring in the temperature range of 100-200 degrees C, 480-670 degrees C and 1101-1244 degrees C, respectively. The apparent heat capacity and heat requirement for melting of MSWI fly ash were obtained by DSC (Differential Scanning Calorimeter). A thermodynamic modeling to predict the heat requirements for melting process has been presented, and it agrees well with the experimental data. Finally, a zero-order kinetic model of fly ash melting transition was established. The apparent activation energy of MSWI fly ash melting transition was obtained. PMID- 17346959 TI - Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors. AB - In this report, we describe new HDAC inhibitors designed to exploit a unique sub pocket in the HDAC8 active site. These compounds were based on inspection of the available HDAC8 crystal structures bound to various inhibitors, which collectively show that the HDAC8 active site is unusually malleable and can accommodate inhibitor structures that are distinct from the canonical 'zinc binding group-linker-cap group' structures of SAHA, TSA, and similar HDAC inhibitors. Some inhibitors based on this new scaffold are >100-fold selective for HDAC8 over other class I and class II HDACs with IC(50) values <1microM against HDAC8. Furthermore, treatment of human cells with the inhibitors described here shows a unique pattern of hyperacetylated proteins compared with the broad-spectrum HDAC inhibitor TSA. PMID- 17346960 TI - Synthesis of the new pseudo-symmetrical tamoxifen derivatives and their anti tumor activity. AB - Three new pseudo-symmetrical tamoxifen derivatives, RID-B (15), C (16), and D (17), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of the pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 15 strongly inhibits the viability of HL-60 human acute promyelocytic leukemia, whereas 16 possesses medium activity against the cell line and 17 has no effect on the cell viability. The agarose gel electrophoresis for DNA cleavage showed the cell death might be induced by apoptosis. PMID- 17346961 TI - Hybrid molecules containing benzo[4,5]imidazo[1,2-d][1,2,4]thiadiazole and alpha bromoacryloyl moieties as potent apoptosis inducers on human myeloid leukaemia cells. AB - The synthesis and biological activity of a series of hybrids 1-5 prepared combining a benzo[4,5]imidazo[1,2-d][1,2,4]thiadiazole and different benzoheterocyclic alpha-bromoacryloyl amides have been described and their structure-activity relationships discussed. All these hetero-bifunctional compounds were highly cytotoxic against the human myeloid leukaemia cell lines HL 60 and U937 (IC(50) 0.24-1.72microM), significantly superior to that of both alkylating units alone. In human myeloid leukaemia HL-60 cells we observed that these compounds suppress survival and proliferation by triggering morphological changes and internucleosomal DNA fragmentation characteristic of apoptotic cell death. The apoptosis induced by these compounds is mediated by caspase-3 activation and is also associated to an early release of cytochrome c from the mitochondria. PMID- 17346962 TI - Benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ischemic reperfusion injury. AB - A novel series of benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines were designed and synthesized as Na(+)/H(+)exchanger inhibitors. Most of them were found to inhibit NHE1-mediated platelet swelling in a concentration-dependent manner, and to have significant cardioprotective effect against myocardial ischemic-reperfusion injury, among which compounds 10a and 34 were more potent than cariporide in both in vivo and in vitro tests. PMID- 17346963 TI - Quercinol, an anti-inflammatory chromene from the wood-rotting fungus Daedalea quercina (Oak Mazegill). AB - The fungus Daedalea quercina (oak mazegill) was examined for its capability of producing antioxidative and anti-inflammatory compounds. Bioactivity guided fractionation of the extract from a mycelial culture led to the isolation of quercinol, which was identified as (-)-(2S)-2-hydroxymethyl-2-methyl-6 hydroxychromene 1 by NMR and X-ray analyses. The cryptic hydroquinone 1 shows a broad anti-inflammatory activity against cyclooxygenase 2 (COX-2), xanthine oxidase (XO), and horseradish peroxidase (HRP) at micromolar concentrations. PMID- 17346964 TI - Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors. AB - N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also inhibits other physiologically relevant isoforms, such as the tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34microM). In order to understand the binding of this inhibitor to the enzyme active site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide adduct was resolved. The inhibitor coordinates to the active site zinc ion by the ionized primary amino group, participating in an extended network of hydrogen bonds with amino acid residues Thr199, Thr200 and two water molecules. The additional two hydrogen bonds in which N hydroxysulfamide bound to hCA II is involved as compared to the corresponding adduct of sulfamide may explain its higher affinity for the enzyme, also providing hints for the design of tight-binding CA inhibitors possessing an organic moiety substituting the NH group in the N-hydroxysulfamide structure. PMID- 17346965 TI - PER3 polymorphism predicts sleep structure and waking performance. AB - Circadian rhythmicity and sleep homeostasis interact to regulate sleep-wake cycles [1-4], but the genetic basis of individual differences in sleep-wake regulation remains largely unknown [5]. PERIOD genes are thought to contribute to individual differences in sleep timing by affecting circadian rhythmicity [6], but not sleep homeostasis [7, 8]. We quantified the contribution of a variable number tandem-repeat polymorphism in the coding region of the circadian clock gene PERIOD3 (PER3) [9, 10] to sleep-wake regulation in a prospective study, in which 24 healthy participants were selected only on the basis of their PER3 genotype. Homozygosity for the longer allele (PER3(5/5)) had a considerable effect on sleep structure, including several markers of sleep homeostasis: slow wave sleep (SWS) and electroencephalogram (EEG) slow-wave activity in non-rapid eye movement (non-REM) sleep and theta and alpha activity during wakefulness and REM sleep were all increased in PER3(5/5) compared to PER3(4/4) individuals. In addition, the decrement of cognitive performance in response to sleep loss was significantly greater in the PER3(5/5) individuals. By contrast, the circadian rhythms of melatonin, cortisol, and peripheral PER3 mRNA expression were not affected. The data show that this polymorphism in PER3 predicts individual differences in the sleep-loss-induced decrement in performance and that this differential susceptibility may be mediated by its effects on sleep homeostasis. PMID- 17346966 TI - LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins. AB - Neurons are polarized cells that contain distinct sets of proteins in their axons and dendrites. Synaptic vesicles (SV) and many SV proteins are exclusively localized in the presynaptic regions but not in dendrites. Despite their fundamental importance, the mechanisms underlying the polarized localization of SV proteins remain unclear. The transparent nematode Caenorhabditis elegans can be used to examine sorting and transport of SV proteins in vivo. Here, we identify a novel protein kinase LRK-1, a C. elegans homolog of the familial Parkinsonism gene PARK8/LRRK2 that is required for polarized localization of SV proteins. In lrk-1 deletion mutants, SV proteins are localized to both presynaptic and dendritic endings in neurons. This aberrant localization of SV proteins in the dendrites is dependent on the AP-1 mu1 clathrin adaptor UNC-101, which is involved in polarized dendritic transport, but not on UNC-104 kinesin, which is required for the transport of SV to presynaptic regions. The LRK-1 proteins are localized in the Golgi apparatus. These results suggest that the LRK 1 protein kinase determines polarized sorting of SV proteins to the axons by excluding SV proteins from the dendrite-specific transport machinery in the Golgi. PMID- 17346967 TI - Attentional load modulates responses of human primary visual cortex to invisible stimuli. AB - Visual neuroscience has long sought to determine the extent to which stimulus evoked activity in visual cortex depends on attention and awareness. Some influential theories of consciousness maintain that the allocation of attention is restricted to conscious representations [1, 2]. However, in the load theory of attention [3], competition between task-relevant and task-irrelevant stimuli for limited-capacity attention does not depend on conscious perception of the irrelevant stimuli. The critical test is whether the level of attentional load in a relevant task would determine unconscious neural processing of invisible stimuli. Human participants were scanned with high-field fMRI while they performed a foveal task of low or high attentional load. Irrelevant, invisible monocular stimuli were simultaneously presented peripherally and were continuously suppressed by a flashing mask in the other eye [4]. Attentional load in the foveal task strongly modulated retinotopic activity evoked in primary visual cortex (V1) by the invisible stimuli. Contrary to traditional views [1, 2, 5, 6], we found that availability of attentional capacity determines neural representations related to unconscious processing of continuously suppressed stimuli in human primary visual cortex. Spillover of attention to cortical representations of invisible stimuli (under low load) cannot be a sufficient condition for their awareness. PMID- 17346968 TI - The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression. AB - BACKGROUND: The accurate alignment of chromosomes at the spindle equator is fundamental for the equal distribution of the genome in mitosis and thus for the genetic integrity of eukaryotes. Although it is well established that chromosome movements are coupled to microtubule dynamics, the underlying mechanism is not well understood. RESULTS: By combining RNAi-depletion experiments with in vitro biochemical assays, we demonstrate that the human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression in mammalian tissue culture cells. We show that in vitro Kif18A is a slow plus-end-directed kinesin that possesses microtubule depolymerizing activity. Notably, Kif18A like its yeast ortholog Kip3p depolymerizes longer microtubules more quickly than shorter ones. In vivo, Kif18A accumulates in mitosis where it localizes close to the plus ends of kinetochore microtubules. The depletion of Kif18A induces aberrantly long mitotic spindles and loss of tension across sister kinetochores, resulting in the activation of the Mad2-dependent spindle-assembly checkpoint. Live-cell microscopy studies revealed that in Kif18A-depleted cells, chromosomes move at reduced speed and completely fail to align at the spindle equator. CONCLUSIONS: These studies identify Kif18A as a dual-functional kinesin and a key component of chromosome congression in mammalian cells. PMID- 17346969 TI - Metacognition in the rat. AB - The ability to reflect on one's own mental processes, termed metacognition, is a defining feature of human existence [1, 2]. Consequently, a fundamental question in comparative cognition is whether nonhuman animals have knowledge of their own cognitive states [3]. Recent evidence suggests that people and nonhuman primates [4-8] but not less "cognitively sophisticated" species [3, 9, 10] are capable of metacognition. Here, we demonstrate for the first time that rats are capable of metacognition--i.e., they know when they do not know the answer in a duration discrimination test. Before taking the duration test, rats were given the opportunity to decline the test. On other trials, they were not given the option to decline the test. Accurate performance on the duration test yielded a large reward, whereas inaccurate performance resulted in no reward. Declining a test yielded a small but guaranteed reward. If rats possess knowledge regarding whether they know the answer to the test, they would be expected to decline most frequently on difficult tests and show lowest accuracy on difficult tests that cannot be declined [4]. Our data provide evidence for both predictions and suggest that a nonprimate has knowledge of its own cognitive state. PMID- 17346970 TI - Tolerance allows bonobos to outperform chimpanzees on a cooperative task. AB - To understand constraints on the evolution of cooperation, we compared the ability of bonobos and chimpanzees to cooperatively solve a food-retrieval problem. We addressed two hypotheses. The "emotional-reactivity hypothesis" predicts that bonobos will cooperate more successfully because tolerance levels are higher in bonobos. This prediction is inspired by studies of domesticated animals; such studies suggest that selection on emotional reactivity can influence the ability to solve social problems [1, 2]. In contrast, the "hunting hypothesis" predicts that chimpanzees will cooperate more successfully because only chimpanzees have been reported to cooperatively hunt in the wild [3-5]. We indexed emotional reactivity by measuring social tolerance while the animals were cofeeding and found that bonobos were more tolerant of cofeeding than chimpanzees. In addition, during cofeeding tests only bonobos exhibited socio sexual behavior, and they played more. When presented with a task of retrieving food that was difficult to monopolize, bonobos and chimpanzees were equally cooperative. However, when the food reward was highly monopolizable, bonobos were more successful than chimpanzees at cooperating to retrieve it. These results support the emotional-reactivity hypothesis. Selection on temperament may in part explain the variance in cooperative ability across species, including hominoids. PMID- 17346971 TI - Is low lower-limb kinematic variability always an index of stability? PMID- 17346972 TI - Pathological fracture of the atlas secondary to plasmacytoma. AB - Plasmacytoma of the atlas with pathological fracture has not been previously reported. A 72-year-old man was admitted to our clinic with a 5-month history of occipital headache. Neurologic examination revealed mild occipital neuralgia, difficulty with movements of the cranium, hyperactive deep tendon reflexes, but no Babinski sign. Magnetic resonance imaging (MRI) of the cervical spine showed a 1x2 cm well-circumscribed extradural mass, with lytic destruction and fracture of the lateral mass of C1. Preoperatively dynamic cervical radiographs showed no instability. Using a transcondylar approach, the tumor was removed, and posterolateral fixation and fusion (using iliac autograft) was performed. Biopsy was reported as plasmacytoma. The patient was pain-free with bony fusion 3 years after surgery. This paper presents a pathologic fracture of C1. Although the primary treatment of plasmacytoma is non-surgical, the need for tissue diagnosis in relevant areas may dictate an open biopsy procedure. Such cases may require a decompression and reconstruction procedure. PMID- 17346973 TI - Solitary intracranial subdural osteoma: intraoperative findings and primary anastomosis of an involved cortical vein. AB - We report a patient with a intracranial subdural osteoma with a large cortical vein passing through the subdural calcified mass. A 60-year-old man presented with an approximately 3-year history of persistent headache. Computerized tomography (CT) scanning showed a homogeneous high-density nodule attached to the inner surface of the right frontal skull. Intraoperatively, the hard mass was found to be located in the intradural subarachnoid space. A large cortical vein passed through the subdural mass and was anastomosed in an end-to-end fashion after the excision of the segment involved by the tumor. The histopathologic examination showed lamellated bony trabeculae lined by osteoblasts and the underlying dura was uninvolved by the tumor cells. PMID- 17346974 TI - Subtemporal approach for a P2-P3 junction aneurysm of the posterior cerebral artery. AB - Aneurysms are seen rarely at the P2-P3 junction of the posterior cerebral artery (PCA). P2-P3 junction aneurysm surgery is challenging. Here, a successful clipping of a large P2-P3 junction aneurysm via a subtemporal approach is reported. A 26-year-old woman presented with a 6-month history of left occipito parietal headache. Computed tomography (CT) scan, magnetic resonance imaging (MRI) and cerebral angiography revealed a 2-cm aneurysm at the P2-P3 junction of the left PCA. Successful neck clipping of the aneurysm was performed via a subtemporal approach without additional neurological deficits or surgical complications. Coil embolization has been suggested as the treatment of choice but PCA aneurysms are also good candidates for microsurgical clipping. The subtemporal approach is simple and safe in experienced hands. P2-P3 junction PCA aneurysms can be successfully clipped via the subtemporal approach without excessive brain retraction, resection of brain tissue or disruption of surface veins. PMID- 17346975 TI - The effect of caffeine on dilated cerebral circulation and on diagnostic CO2 reactivity testing. AB - Reduction of cerebral blood flow by caffeine has been shown in multiple studies. However, the effect of this substance on pathologically dilated cerebral vessels is not clearly defined. The aim of this study was to investigate the effect of caffeine on an already dilated cerebral circulation and specify if these vessels are still able to constrict as a consequence of caffeine stimulation. A second aim of this study was to compare results of cerebral vasomotor CO(2) reactivity testing with and without caffeine ingestion. Seventeen healthy adult volunteers had vasomotor reactivity tested before and thirty minutes after ingestion of 300 mg of caffeine. Each vasomotor reactivity test consisted of velocity measurements from both middle cerebral arteries using transcranial Doppler ultrasound during normocapnia, hypercapnia, and hypocapnia. Hemodynamic data and end-tidal CO(2) (etCO(2)) concentration were also recorded. The vasomotor reactivity (VMR) and CO(2) reactivity were calculated from a measured data pool. At a level of etCO(2)=40 mmHg the resting velocity in the middle cerebral artery (V(MCA)) dropped from 70.7+/-22.8 cm/sec to 60.7 +/- 15.4 cm/sec 30 minutes after caffeine stimulation (14.1% decrease, p<0.001). During hypercapnia of etCO(2)=50 mmHg there was also a significant decline of V(MCA) from 103.1+/-25.4 to 91.4+/-21.8 cm/sec (11.3%, p<0.001). There was not a statistically significant reduction of V(MCA) during hypocapnia. Calculated VMR and CO(2) reactivity before and after caffeine intake were not statistically significant. The presented data demonstrate a significant decrease in cerebral blood flow velocities after caffeine ingestion both in a normal cerebrovascular bed and under conditions of peripheral cerebrovascular vasodilatation. These findings support the important role of caffeine in regulation of CBF under different pathological conditions. Despite significant reactive vasodilatation in the brain microcirculation, caffeine is still able to act as a competitive antagonist of CO(2) on cerebral microvessels. The fact that caffeine may decrease CBF despite significant pathological vasodilatation offers the possibility of therapeutic manipulation in patients with traumatic vasoparalysis. For routine clinical testing of CO(2) reactivity it is not necessary to insist on pre-test dietary restrictions. PMID- 17346976 TI - Isolated intrasellar tuberculoma mimicking pituitary adenoma. AB - A 37-year-old woman presenting with galactorrhea and menstrual irregularity due to an intrasellar lesion of the pituitary gland underwent transsphenoidal surgery for histopathological diagnosis and removal of the lesion. Histological findings were consistent with a tuberculoma. The post-operative course was satisfactory with resolution of galactorrhea and improved ovulatory cycle. The patient was successfully treated with a combination of surgical resection and anti tuberculous therapy for one year, which resulted in hormonal and tuberculosis control. This patient appears unique regarding the location of the lesion and the dramatic response to surgical treatment. Although differential diagnosis of inflammatory pathologies of the intrasellar region presents difficulties, this patient demonstrates that tuberculoma should be considered. PMID- 17346977 TI - Improved automated synthesis of [18F]fluoroethylcholine as a radiotracer for cancer imaging. AB - [(18)F]Fluoroethylcholine has been recently introduced as a promising (18)F labelled analogue of [(11)C]choline which had been previously described as a tracer for metabolic cancer imaging with positron emission tomography (PET). Due to the practical advantages of using the longer-lived radioisotope (18)F (t(1/2)=110 min), offering the opportunity of a more widespread clinical application, we established a reliable, fully automated synthesis for its production using a modified, commercially available module. [(18)F]Fluoroethylcholine was prepared from N,N-dimethylaminoethanol by iodide catalyzed alkylation with 1-[(18)F]fluoro-2-tosylethane as alkylating agent, resulting in a total radiochemical yield of 30+/-6% after a synthesis time of 50 min. The specific activity of [(18)F]fluoroethylcholine was >55 GBq/micromol and the radiochemical purity 95-99%. PMID- 17346978 TI - Optimized FIB silicon samples suitable for lattice parameters measurements by convergent beam electron diffraction. AB - The aim of this paper is to check the effect of artefacts introduced by focused ion beam (FIB) milling on the strain measurement by convergent beam electron diffraction (CBED). We show that on optimized silicon FIB samples, the strain measurement can be performed with a sensitivity of about 2.5 x 10(-4) which is very close to the theoretical one and we conclude that FIB preparation can be suitable for such measurements in microelectronic devices. To achieve this, we first used CBED and electron energy loss spectroscopy (EELS) which provide a procedure permitting an exact knowledge of the sample geometry, i.e. the thickness of both amorphous and crystalline layers. This procedure was used in order to measure the FIB-amorphized sidewall layer. It was found that if the FIB preparation is optimized one can reduce this amorphous layer down to around 7 nm on each side. Secondly different preparation techniques (cleavage, Tripodtrade mark and FIB) permit to check if the surface damaged layer introduced by FIB influences the strain state of the sample. Finally, it was found that the damaged layer does not introduce measurable strain in pure silicon but reduces appreciably the quality of the CBED patterns. PMID- 17346979 TI - Verifying the operational set-up of a radionuclide air-monitoring station. AB - A worldwide radionuclide network of 80 stations, part of the International Monitoring System, was designed to monitor compliance with the Comprehensive Nuclear-Test-Ban Treaty. After installation, the stations are certified to comply with the minimum requirements laid down by the Preparatory Commission of the Comprehensive Nuclear-Test-Ban Treaty Organization. Among the several certification tests carried out at each station, the verification of the radionuclide activity concentrations is a crucial one and is based on an independent testing of the airflow rate measurement system and of the gamma detector system, as well as on the assessment of the samples collected during parallel sampling and measured at radionuclide laboratories. PMID- 17346980 TI - Human adult olfactory neural progenitors promote axotomized rubrospinal tract axonal reinnervation and locomotor recovery. AB - We investigated the effects of engrafted human adult olfactory neuroepithelial neurosphere forming cells (NSFCs) on regeneration and reinnervation of rubrospinal tract (RST) axons and locomotor recovery following partial cervical hemisection that completely ablated the RST. Weekly behavioral testing showed greater functional recovery of forelimb use during the 12 weeks after NSFCs engraftment than in the control rats. Anterograde tracing with biotinylated dextran amine (BDA) confirmed the presence of RST axons within the white matter 4 8 segments caudal to the grafts. Both immunofluorescence and immunoelectron microscopy revealed the BDA-labeled RST axonal terminals reestablished synaptic connections with motoneurons in the ventral horn of the distal cervical spinal cord. Further study of forelimb functional recovery in NSFCs-engrafted subgroups considered the effects of a second dorsolateral funiculotomy, irreversibly destroying the recovery, and the injection of muscimol, blocking RST neuronal activity reversibly. These results highlight the unique potential of human olfactory neuroepithelial-derived progenitors as an autologous cell source for spinal cord repair. PMID- 17346981 TI - Inhibition of p38 mitogen activated protein kinase activation and mutant SOD1(G93A)-induced motor neuron death. AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective loss of motor neurons. Stress activated protein kinases (SAPK) have been suggested to play a role in the pathogenesis of ALS. We studied the relevance of p38 MAPK for motor neuron degeneration in the mutant SOD1 mouse. Increased levels of phospho-p38 MAPK were present in the motor neurons and microglia of the ventral spinal cord. The p38 MAPK-inhibitor, SB203580, completely inhibited mutant SOD1-induced apoptosis of motor neurons and blocked LPS-induced activation of microglia. Semapimod, a p38 MAPK inhibitor suitable for clinical use, prolonged survival of mutant SOD1 mice to a limited extent, but largely protected motor neurons and proximal axons from mutant SOD1-induced degeneration. Our data confirm the abnormal activation of p38 MAPK in mutant SOD1 mice and the involvement of p38 MAPK in mutant SOD1-induced motor neuron death. We demonstrate the effect of p38 MAPK inhibition on survival of mutant SOD1 mice and reveal a dissociation between the effect on survival of motor neurons and that on survival of the animal, the latter likely depending on the integrity of the entire motor axon. PMID- 17346982 TI - Vipp1 is required for basic thylakoid membrane formation but not for the assembly of thylakoid protein complexes. AB - Vipp1 (vesicle inducing protein in plastids 1) is found in cyanobacteria and chloroplasts where it is essential for thylakoid formation. Arabidopsis thaliana mutant plants with a reduction of Vipp1 to about 20% of wild type content become albinotic at an early stage. We propose that this drastic phenotype results from an inability of the remaining Vipp1 protein to assemble into a homo-oligomeric complex, indicating that oligomerization is a prerequisite for Vipp1 function. A Vipp1-ProteinA fusion protein, expressed in the Deltavipp1 mutant background, is able to reinstate oligomerization and restore photoautotrophic growth. Plants containing Vipp1-ProteinA in amounts comparable to Vipp1 in the wild type exhibit a wild type phenotype. However, plants with a reduced amount of Vipp1-ProteinA protein are growth-retarded and significantly paler than the wild type. This phenotype is caused by a decrease in thylakoid membrane content and a concomitant reduction in photosynthetic activity. To the extent that thylakoid membranes are made in these plants they are properly assembled with protein-pigment complexes and are photosynthetically active. This strongly supports a function of Vipp1 in basic thylakoid membrane formation and not in the functional assembly of thylakoid protein complexes. Intriguingly, electron microscopic analysis shows that chloroplasts in the mutant plants are not equally affected by the Vipp1 shortage. Indeed, a wide range of different stages of thylakoid development ranging from wild-type-like chloroplasts to plastids nearly devoid of thylakoids can be observed in organelles of one and the same cell. PMID- 17346983 TI - Metabolism of brassinosteroids in plants. AB - Brassinosteroids represent a class of plant hormones. More than 70 compounds have been isolated from plants. Currently 42 brassinosteroid metabolites and their conjugates are known. This review describes the miscellaneous metabolic pathways of brassinosteroids in plants. There are some types of metabolic processes involving brassinosteroids in plants: dehydrogenation, demethylation, epimerization, esterification, glycosylation, hydroxylation, side-chain cleavage and sulfonation. Metabolism of brassinosteroids can be divided into two categories: i) structural changes to the steroidal skeleton; and ii) structural changes to the side-chain. PMID- 17346984 TI - Aortoesophageal perforation following ingestion of razorblades with massive haemothorax. AB - Aortoesophageal fistula is a rare complication of foreign body ingestion. Typically having ingested a fish or chicken bone, the patient complains of chest pain or discomfort and/or may present with massive gastrointestinal bleeding, which in all but rare cases is fatal. The pathological mechanism may involve perforation and direct communication of oesophagus and aorta usually at the level of the aortic arch; or more usually following oesophageal perforation, the subsequent mediastinal abscess leads to necrosis of the aortic wall. Torrential haemothorax as a result of such a process has not been previously described, though it has undoubtedly occurred. We present a case of massive haemothorax following deliberate ingestion of razorblades that highlights clinically and radiologically the natural course of such a tragic action. PMID- 17346985 TI - The impact of diffuseness of coronary artery disease on the outcomes of patients undergoing primary and reoperative coronary artery bypass grafting. AB - OBJECTIVE: Diffuse coronary artery disease jeopardizes myocardium, increasing surgical mortality in primary coronary artery bypass grafting (CABG). We sought to determine the impact of diffuseness on pre- and post-discharge outcomes for both primary and reoperative CABG (REOP). METHODS: Using a validated system for measuring diffuseness of coronary disease, preoperative angiograms were scored for primary CABG (n=792) and REOP cases (n=268) performed 1997-2004. A diffuseness score (DS)>18 was defined as elevated. In-hospital mortality, intermediate-term survival, and in-hospital composite outcome (COMP) (one or more of: mortality, stroke, MI, deep sternal infection, sepsis, IABP insertion, or return to OR) were examined. RESULTS: In-hospital mortality and COMP for patients with DS>18 were significantly higher (7.9% vs 2.4%, p<0.0001), (17.8% vs 9.2%, p<0.0001). DS (mean+/-SD) was higher in REOP cases than primary CABG (18.9+/-7.1 vs 14.4+/-6.0, p<0.0001). By multivariate analysis, DS>18 (OR 2.00, 95%CI, 1.20 3.32, p=0.008) and REOP (OR 2.40, 95%CI, 1.53-3.77, p<0.0001) were independently associated with COMP. Using propensity scores 82% of cases with DS>18 (n=289) were matched 1:1 to cases with DS18 (6.9% vs 2.8%, p=0.02), (16.6% vs 10.4%, p=0.03). Comparing cases with DS18 and primary CABG versus REOP, survival at 2 years was 92.1% versus 84.5% (p=0.001) and 92.7% versus 82.7% (p<0.0001), respectively. CONCLUSIONS: Diffuse coronary artery disease is an important predictor of morbidity and mortality in primary and REOP CABG patients, and should be considered in both individual patient assessment and risk adjustment. PMID- 17346986 TI - Alkali metal-cationized serine clusters studied by sonic spray ionization tandem mass spectrometry. AB - Serine solutions containing salts of alkali metals yield magic number clusters of the type (Ser(4)+C)(+), (Ser(8)+C)(+), (Ser(12)+C)(+), and (Ser(17)+2C)(+2) (where C = Li(+), Na(+), K(+), Rb(+), or Cs(+)), in relative abundances which are strongly dependent on the cation size. Strong selectivity for homochirality is involved in the formation of serine tetramers cationized by K(+), Rb(+), and Cs(+). This is also the case for the octamers cationized by the smaller alkalis but there is a strong preference for heterochirality in the octamers cationized by the larger alkali cations. Tandem mass spectrometry shows that the octamers and dodecamers cationized by K(+), Rb(+), and Cs(+) dissociate mainly by the loss of Ser(4) units, suggesting that the neutral tetramers are the stable building blocks of the observed larger aggregates, (Ser(8)+C)(+) and (Ser(12)+C)(+). Remarkably, although the Ser(4) units are formed with a strong preference for homochirality, they aggregate further regardless of their handedness and, therefore, with a preference for the nominally racemic 4D:4L structure and an overall strong heterochiral preference. The octamers cationized by K(+), Rb(+), or Cs(+) therefore represent a new type of cluster ion that is homochiral in its internal subunits, which then assemble in a random fashion to form octamers. We tentatively interpret the homochirality of these tetramers as a consequence of assembly of the serine molecules around a central metal ion. The data provide additional evidence that the neutral serine octamer is homochiral and is readily cationized by smaller ions. PMID- 17346987 TI - Sitting versus standing: does the intradiscal pressure cause disc degeneration or low back pain? AB - Studies of lumbar intradiscal pressure (IDP) in standing and upright sitting have mostly reported higher pressures in sitting. It was assumed clinically that flexion of the lumbar spine in sitting relative to standing, caused higher IDP, disc degeneration or rupture, and low back pain. IDP indicates axial compressive load upon a non-degenerate disc, but provides little or no indication of shear, axial rotation or bending. This review is presented in two main parts. First, in vivo IDP data in standing and upright sitting for non-degenerate discs are comprehensively reviewed. As methodology, results and interpretations varied between IDP studies, in vivo studies measuring spinal shrinkage and spinal internal-fixator loads to infer axial compressive load to the discs are also reviewed. When data are considered together, it is clear that IDP is often similar in standing and sitting. Secondly, clinical assumptions related to IDP in sitting are considered in light of basic and epidemiologic studies. Current studies indicate that IDP in sitting is unlikely to pose a threat to non degenerate discs, and sitting is no worse than standing for disc degeneration or low back pain incidence. If sitting is a greater threat for development of low back pain than standing, the mechanism is unlikely to be raised IDP. PMID- 17346988 TI - Item analysis in functional magnetic resonance imaging. AB - Behavioral and neuroimaging studies of cognition frequently test hypotheses regarding mental processing of different stimulus categories (e.g. verbs, faces, animals, scenes, etc.). The conclusions of such studies hinge upon the generalizability of their findings from the specific stimuli used in the experiment to the category as a whole. This type of generalizability is explicitly tested in behavioral studies, using "item analysis". However, generalizability to stimulus categories has up until now been assumed in neuroimaging studies, without employing item analysis for statistical validation. Here we apply item analysis to a functional magnetic resonance imaging study of nouns and verbs, demonstrating its theoretical importance and feasibility. In the subject-wise analysis, a left prefrontal and a left posterior-temporal region of interest showed putative grammatical class effects. An item-wise analysis revealed, however, that only the left posterior-temporal effect was generalizable to the stimulus categories of nouns and verbs. Taken together, the findings of the subject- and item-wise analyses suggest that grammatical-class effects in the left prefrontal cortex depend on the particular word stimuli used, rather than reflecting categorical differences between nouns and verbs. This empirical example illustrates that item analysis not only is sufficiently powered to detect task relevant changes in BOLD signal but also can make theoretically important distinctions between findings that generalize to the item populations, and those that do not. PMID- 17346989 TI - Mental rotation and object categorization share a common network of prefrontal and dorsal and ventral regions of posterior cortex. AB - The multiple-views-plus-transformation variant of object model verification theories predicts that parietal regions that are critical for mental rotation contribute to visual object cognition. Some neuroimaging studies have shown that the intraparietal sulcus region is critically involved in mental rotation. Other studies indicate that both ventral and dorsal posterior regions are object sensitive and involved in object perception and categorization tasks. However, it is unknown whether dorsal object-sensitive areas overlap with regions recruited for object mental rotation. Functional magnetic resonance imaging was used to test this directly. Participants performed standard tasks of object categorization, mental rotation, and eye movements. Results provided clear support for the prediction, demonstrating overlap between dorsal object-sensitive regions in ventral-caudal intraparietal sulcus (vcIPS) and an adjacent dorsal occipital area and the regions that are activated during mental rotation but not during saccades. In addition, object mental rotation (but not saccades) activated object-sensitive areas in lateral dorsal occipitotemporal cortex (DOT), and both mental rotation and object categorization recruited ventrolateral prefrontal cortex areas implicated in attention, working memory, and cognitive control. These findings provide clear evidence that a prefrontal-posterior cortical system implicated in mental rotation, including the occipitoparietal regions critical for this spatial task, is recruited during visual object categorization. Altogether, the findings provide a key link in understanding the role of dorsal and ventral visual areas in spatial and object perception and cognition: Regions in occipitoparietal cortex, as well as DOT cortex, have a general role in visual object cognition, supporting not only mental rotation but also categorization. PMID- 17346991 TI - Multilocus phylogenetic analyses within Blumeria graminis, a powdery mildew fungus of cereals. AB - Blumeria graminis, a powdery mildew fungus, is an important plant pathogen that causes serious damage to a variety of cereal crops. In spite of the importance of the pathogen, information on phylogenetic structure within B. graminis is scarce. In this study we conducted phylogenetic analyses of B. graminis based on the DNA sequences of four different DNA regions (ITS, 28S rDNA, chitin synthase 1, and beta-tubulin). The analyses revealed that the protein-coding regions have higher amounts of phylogenetic signals than rDNA regions and are useful for phylogenetic analyses of B. graminis. The present phylogenetic analyses revealed nine distinct groups in the B. graminis isolates used in this study, a result which was commonly supported by all trees constructed from the four DNA regions. Isolates from a single host genus belonged to a single group except for isolates from Lolium and Bromus, in which the isolates were split into two and three groups, respectively. Isolates from Agropyron, Secale and Triticum formed a distinct clade (Triticum clade) with identical or similar DNA sequences. The Hordeum clade was a sister of the Triticum clade, and Poa and Avena clades were distantly related to the Triticum and Hordeum clades. This phylogenetic relationship of B. graminis is well concordant with the level of reproductive isolation between formae speciales and also with phylogeny inferred from a cytological study. Shimodaira-Hasegawa and Templeton tests using sequences of four different DNA regions significantly rejected the tree topology of plants. Therefore, possibility of co-speciation between B. graminis and its host plants was obscure in this study. PMID- 17346990 TI - A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: evidence for genetic and environmental heterogeneity in the developing brain. AB - Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD. PMID- 17346992 TI - Molecular phylogeny and biogeography of the Antillean geckos Phyllodactylus wirshingi, Tarentola americana, and Hemidactylus haitianus (Reptilia, Squamata). PMID- 17346994 TI - RETRACTED: Modified high-performance liquid chromatographic conditions for determination of inosine 5'-monophosphate dehydrogenase activity inerythrocytes. AB - This article has been retracted consistent with Elsevier Policy on Article Withdrawal, because three of the named authors (N. E., G. E., and G.E. J.-S.) have not been kept informed about the publication and have not agreed to publish the study. Please see http://www.elsevier.com/locate/withdrawalpolicy. The Publisher apologizes for any inconvenience this may cause. PMID- 17346993 TI - Species boundaries and phylogenetic relationships within the green algal genus Codium (Bryopsidales) based on plastid DNA sequences. AB - Despite the potential model role of the green algal genus Codium for studies of marine speciation and evolution, there have been difficulties with species delimitation and a molecular phylogenetic framework was lacking. In the present study, 74 evolutionarily significant units (ESUs) are delimited using 227 rbcL exon 1 sequences obtained from specimens collected throughout the genus' range. Several morpho-species were shown to be poorly defined, with some clearly in need of lumping and others containing pseudo-cryptic diversity. A phylogenetic hypothesis of 72 Codium ESUs is inferred from rbcL exon 1 and rps3-rpl16 sequence data using a conventional nucleotide substitution model (GTR+Gamma+I), a codon position model and a covariotide (covarion) model, and the fit of a multitude of substitution models and alignment partitioning strategies to the sequence data is reported. Molecular clock tree rooting was carried out because outgroup rooting was probably affected by phylogenetic bias. Several aspects of the evolution of morphological features of Codium are discussed and the inferred phylogenetic hypothesis is used as a framework to study the biogeography of the genus, both at a global scale and within the Indian Ocean. PMID- 17346995 TI - Changes in composition and activities of 26S proteasomes under the action of doxorubicin--apoptosis inductor of erythroleukemic K562 cells. AB - Changes in the subunit composition, phosphorylation of the subunits, and regulation of the activities of 26S proteasomes in proliferating cells undergoing programmed cell death have not been studied so far. Moreover, there are no reports on phosphorylation of proteasome subunits both in normal and in neoplastic cells during apoptosis. The data of the present study show for the first time that apoptosis inductor doxorubicin regulates subunit composition, enzymatic activities, and phosphorylation state of 26S proteasomes in neoplastic (proerythroleukemic K562) cells or, in other words, induces reprogramming of proteasome population. Furthermore, the phosphorylation state of proteasomes is found to be the mechanism controlling specificity of proteasomal proteolytic and endoribonuclease activities. PMID- 17346996 TI - The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. AB - Sphingosine-1-phosphate, a key mediator in immune cell trafficking, is elevated in the lungs of asthmatic patients and regulates pulmonary epithelium permeability. Stimulation of mast cells by allergens induces two mammalian sphingosine kinases (Sphk1 and Sphk2) to produce sphingosine-1-phosphate (S1P). Little is known about the individual role of these kinases in regulating immune cell function. Here we show that in mast cells, Sphk2 is required for production of S1P, for calcium influx, for activation of protein kinase C, and for cytokine production and degranulation. However, susceptibility to in vivo anaphylaxis is determined both by S1P within the mast cell compartment and by circulating S1P generated by Sphk1 predominantly from a non-mast cell source(s). Thus, sphingosine kinases are determinants of mast cell responsiveness, demonstrating a previously unrecognized relationship with anaphylaxis. PMID- 17346998 TI - Introducing reptiles into a captive collection: the role of the veterinarian. AB - The successful introduction of reptiles into a captive collection depends on providing optimal husbandry and veterinary attention. An important role of the veterinarian in this process is the prevention of disease introduction, which may affect both the introduced and the resident animals. This review focuses on preventive veterinary medicine in reptiles, emphasising quarantine measures, disinfection and entry control for infectious agents. Agents discussed include those that are likely give rise to severe clinical problems on introduction into a collection of reptiles, or, in the case of Salmonella, those that pose a significant public health risk. Aetiology, clinical signs and diagnosis are discussed for the most relevant endo- and ectoparasites, bacteria and viruses including Cryptosporidium and Entamoeba, Salmonella, Dermabacter, Chlamydiales, Mycoplasma, Herpesvirus, Adenovirus, Paramyxovirus and inclusion body disease. PMID- 17346997 TI - The stimulatory potency of T cell antigens is influenced by the formation of the immunological synapse. AB - T cell activation is predicated on the interaction between the T cell receptor and peptide-major histocompatibility (pMHC) ligands. The factors that determine the stimulatory potency of a pMHC molecule remain unclear. We describe results showing that a peptide exhibiting many hallmarks of a weak agonist stimulates T cells to proliferate more than the wild-type agonist ligand. An in silico approach suggested that the inability to form the central supramolecular activation cluster (cSMAC) could underlie the increased proliferation. This conclusion was supported by experiments that showed that enhancing cSMAC formation reduced stimulatory capacity of the weak peptide. Our studies highlight the fact that a complex interplay of factors determines the quality of a T cell antigen. PMID- 17346999 TI - Newborns at risk for special education placement: a population-based study. AB - OBJECTIVES: To establish the contributions of birth weight (BW), gender, socioeconomic status (SES), and parental age on risks for special education (SE) placements in school-age children. METHODS: A population-based sample of 900 school-age children attending the following full-time SE groups: at level 1, children had isolated neurodevelopmental, physical, or other impairments; at level 2, borderline to mild intellectual disability (ID); and at level 3, moderate to severe ID. Three hundred and one children enrolled in mainstream education formed the control group (level 0). For all children with siblings, we defined familiar forms of learning disorders as having a sibling in one of the SE groupings. We performed our analysis for the entire cohort as well as comparing risk factors within the familial and non-familial types of SE groupings. RESULTS: In multinomial logistic regression analysis, age of father 40 years, low BW (<2500g or <-2 SD), male sex, and parent's lower SES, all increased the probability of SE placement. In the familial forms of levels 2 and 3, the parental SES was lower and, in addition, in the level 2, the family size was bigger. Furthermore, in the non-familial form of level 2, both the low and the high (4000g) BW were more common. CONCLUSIONS: Among the known risk factors for learning disabilities (LD), our study highlighted the importance of a higher paternal age and a lower SES especially in the familial forms of LD. PMID- 17347000 TI - TROSY of side-chain amides in large proteins. AB - By using the mixed solvent of 50% H2O/50% D2O and employing deuterium decoupling, TROSY experiments exclusively detect NMR signals from semideuterated isotopomers of carboxamide groups with high sensitivities for proteins with molecular weights up to 80 kDa. This isotopomer-selective strategy extends TROSY experiments from exclusively detecting backbone to both backbone and side-chain amides, particularly in large proteins. Because of differences in both TROSY effect and dynamics between 15N-H(E){D(Z)} and 15N-H(Z){D(E)} isotopomers of the same carboxamide, the 15N transverse magnetization of the latter relaxes significantly faster than that of the former, which provides a direct and reliable stereospecific distinction between the two configurations. The TROSY effects on the 15N-H(E){D(Z)} isotopomers of side-chain amides are as significant as on backbone amides. PMID- 17347001 TI - P.E.HSQC: a simple experiment for simultaneous and sign-sensitive measurement of (1JCH+DCH) and (2JHH+DHH) couplings. AB - The angular information content of residual dipolar couplings between nuclei of fixed distance makes the accurate and sign-sensitive measurement of (1JCH+DCH) and (2JHH+DHH) couplings highly desirable. Experiments published so far are typically highly specialized for the effective measurement of a subset of couplings. The P.E.HSQC presented here, is an E.COSY based experiment which allows the simultaneous measurement of all heteronuclear and homonuclear couplings within CH, CH2, and CH3 groups in a single spectrum with the necessary precision and sign information. The simplicity of the approach and the absence of artefacts like phase distortions due to antiphase evolution make it ideally suited for coupling determination of organic molecules at natural abundance. PMID- 17347002 TI - Endothermic heart rate response in broiler and White Leghorn chicks (Gallus gallus domesticus) during the first two days of post-hatch life. AB - The embryonic modal value of heart rate (MHR) differs between broiler and White Leghorn chickens, but the initial development of cholinergic chronotropic control of embryonic heart rate (HR) does not. Thus, we hypothesized that hatchling MHR should also differ between broiler and White Leghorn strains, while the development of a physiological regulation, such as the endothermic HR response, should not be different between hatchlings of the two strains. To test this, we measured the response of HR and cloaca temperature (Tb) to alteration of ambient temperature (Ta); i.e., 35 degrees C-25 degrees C-35 degrees C, in four groups of hatchlings on Days 0 and 1 post-hatch. Fertile eggs of both strains with similar mass were incubated simultaneously in the same incubator. Eggs of broiler chickens hatched approximately 7 h earlier than White Leghorn chicken eggs. Chick mass at hatching was identical in both strains, but diverged during 2 days after hatching. Tb measured at the initial Ta of 35 degrees C was identical in both strains. MHR at the same Ta was approximately 30 bpm lower in broiler chicks than in White Leghorn chicks, but the difference was reversed to that observed in the embryos. The endothermic HR response was advanced by approximately 1 day in broiler chicks compared with White Leghorn chicks. As a result, eggs of similar mass in both strains produced chicks with similar mass and Tb at hatching, but during 2 days of post-hatch life their masses diverged and regulation of the endothermic HR response developed earlier in broiler than in White Leghorn hatchlings. This physiological heterochrony between strains is most likely due to genetic selection for fast growth in broiler chickens. PMID- 17347003 TI - Evolution of the placenta during the early radiation of placental mammals. AB - The chorioallantoic placenta is an organ of gaseous exchange that exhibits a high degree of structural diversity. One factor determining oxygen transfer across the placenta, the diffusion distance, is in part dependent on the number of cell layers separating maternal from fetal blood. This interhaemal barrier occurs in three principal variants. The focus of this review is on determining how the barrier evolved in placental mammals. The analysis was based on current knowledge of placental structure, as far as possible using ultrastructural data, and on current views about the evolution of placental mammals, derived from molecular phylogenetics. We show that epitheliochorial placentation, the least invasive type, is a derived state and discuss factors that may have determined its evolution with reference to conflict theory, as applied to the allocation of resources between mother and fetus. It is not yet possible to determine which of the two more invasive types of placentation occurred in the last common ancestor of crown placentals. Depending on tree topology and taxon sampling, the result achieved is either endotheliochorial, haemochorial or unresolved. Finally we discuss other factors important to placental gas exchange and point to physiological variables that might become amenable to phylogenetic analysis. PMID- 17347004 TI - The effect of environmental salinity on the protein expression of Na+/K+-ATPase, Na+/K+/2Cl- cotransporter, cystic fibrosis transmembrane conductance regulator, anion exchanger 1, and chloride channel 3 in gills of a euryhaline teleost, Tetraodon nigroviridis. AB - Chloride transport mechanisms in the gills of the estuarine spotted green pufferfish (Tetraodon nigroviridis) were investigated. Protein abundance of Na(+)/K(+)-ATPase (NKA) and the other four chloride transporters, i.e., Na(+)/K(+)/2Cl(-) cotransporter (NKCC), cystic fibrosis transmembrane conductance regulator (CFTR), Cl(-)/HCO(3)(-) anion exchanger 1 (AE1), and chloride channel 3 (CLC-3) in gills of the seawater- (SW; 35 per thousand) or freshwater (FW) acclimatized fish were examined by immunoblot analysis. Appropriate negative controls were used to confirm the specificity of the antibodies to the target proteins. The relative protein abundance of NKA was higher (i.e., 2-fold) in gills of the SW group compared to the FW group. NKCC and CFTR were expressed in gills of the SW group but not in the FW group. In contrast, the levels of relative protein abundance of branchial AE1 and CLC-3 in the FW group were 23 fold and 2.7-fold higher, respectively, compared to those of the SW group. This study is first of its kind to provide direct in vivo evidence of the protein expression of CLC-3 in teleostean gills, as well as to examine the simultaneous protein expression of the Cl(-) transporters, especially AE1 and CLC-3 of FW- and SW-acclimatized teleosts. The differential protein expression of NKA, chloride transporters in gills of the FW- and SW-acclimatized T. nigroviridis observed in the present study shows their close relationship to the physiological homeostasis (stable blood osmolality), as well as explains the impressive ionoregulatory ability of this euryhaline species in response to salinity challenges. PMID- 17347005 TI - Does fluctuating thermal regime trigger free amino acid production in the parasitic wasp Aphidius colemani (Hymenoptera: Aphidiinae)? AB - When stressful cold-exposure is interrupted by short warm intervals, physiological recovery is possible, and this improves markedly the survival of insects. Fluctuating thermal regime (FTR) may act as a cue triggering the initiation of a metabolic response involving synthesis of cryoprotective compounds, such as free amino acids (FAA). Since specific changes in FAA levels can provide a good indication of the overall response of an organism to stressful conditions, we investigated temporal changes in FAA body contents of the parasitoid Aphidius colemani Viereck during exposure to FTR (4 degrees C: 20 degrees C for 22 h: 2 h per day) versus constant low temperature (4 degrees C). Physiological response during cold-exposure was clearly dissimilar between thermal treatments. Under constant cold-exposure FAA pool increased, whereas it decreased with cold-exposure duration in FTR. No single FAA accumulation could explain the higher survival under FTR. We propose that instead of considering FAA as a part of cryoprotective arsenal, FAA accumulation should rather be regarded as a symptom of a cold-induced physiological response. This is much less manifest under FTR, as the warm intervals likely allow a periodic reactivation of normal metabolic activities and a recovery of developmental processes. PMID- 17347006 TI - Intraperitoneal and dietary administration of astaxanthin in rainbow trout (Oncorhynchus mykiss)--plasma uptake and tissue distribution of geometrical E/Z isomers. AB - Astaxanthin enters circulation in salmonid fishes upon intraperitoneal injection (IP) of small doses. Blood uptake and tissue distribution of geometrical E/Z astaxanthin isomers were determined in tissues and plasma of duplicated groups of rainbow trout (Oncorhynchus mykiss, initial weight 550 g) some of which were administered high doses of astaxanthin by IP in a trial lasting for 8 weeks. Doses of 10 (IP10), 50 (IP50) or 100 mg (IP100) astaxanthin (Lucantin Pink, BASF, Germany), respectively, dispersed in phosphate buffered saline were tested in comparison with diets containing 10 (Control) or 60 (Fed 60) mg astaxanthin kg( 1). Astaxanthin concentrations in all examined tissues and plasma were significantly higher in IP50 and IP100 than in controls and Fed 60 (p<0.05). In IP50, 11 mg astaxanthin kg(-1) muscle was detected after 4 weeks, compared to 4 mg kg(-1) in rainbow trout fed 60 mg kg(-1). Concentrations up to 80 and 100 mg astaxanthin kg(-1) were detected in liver and kidney after IP, respectively, whereas fish only fed astaxanthin contained about 2 mg astaxanthin kg(-1). No increase in muscle astaxanthin concentration was found between 4 and 8 weeks in fish given IP, and the muscle astaxanthin concentration in IP50 and IP100 were similar. Muscle concentration and injected dose were curvilinearly correlated and the proportion of ingested dose retained by the muscle was negatively correlated with the amount of injected astaxanthin. Plasma and muscle concentrations of astaxanthin were highly correlated (p<0.0001). Astaxanthin Z-isomers accumulated selectively in the various tissues after IP, whereas all-E-astaxanthin was preferably absorbed into plasma when administered via the diet. There was a selective uptake of all-E-astaxanthin in the muscle of all fish. Mortality was not affected by treatment, but a dose-dependent reduction in SGR was evident after IP. In conclusion, a more rapid and higher uptake of astaxanthin in plasma, muscle, kidney and liver of rainbow trout takes place after IP compared to when astaxanthin is fed via the diet. PMID- 17347007 TI - Tissue distribution and characterization of cholinesterase activity in six earthworm species. AB - To validate cholinesterase activity as a biomarker of pesticide exposure, we characterized the tissue distribution (whole body, nervous tissue and crop/gizzard), activity at two seasons of cholinesterase in six different species of earthworms collected in an unpolluted field: Lumbricus terrestris, Lumbricus castaneus, Aporrectodea nocturna, Aporrectodea caliginosa, Allolobophora chlorotica and Aporrectodea rosea. The major part of total cholinesterase activity was found in the nervous tissue while activity in crop/gizzard was weak. The level of the total cholinesterase activity was stable for each species considered throughout the year (spring and autumn). Lumbricus species exhibited three-fold higher specific activity than the others (0.086+/-0.015 U mg(-1) and 0.235+/-0.036 U mg(-1) for Allolobophora or Aporrectodea, and Lumbricus species respectively). This stability of the base level makes cholinesterase activity a useful biomarker for monitoring effects of pesticide under natural conditions. Cholinesterase activity was characterized using different substrates and inhibitors. It seems likely that the cholinesterases are acetylcholinesterases in most species investigated as they preferentially hydrolyzed acetylthiocholine and were inhibited by eserine, but not by tetraisopropyl pyrophoramide (iso-OMPA). Characterization of cholinesterase from Allolobophora chlorotica is uncertain and it cannot be classified as a true AChE. PMID- 17347008 TI - Comparative molecular characterization of ADSS1 and ADSS2 genes in pig (Sus scrofa). AB - Adenylosuccinate synthetase (ADSS) catalyzes the key step of AMP synthesis. Vertebrates have two isozymes of ADSS, which are named ADSS1 and ADSS2, respectively. In this study, we cloned porcine ADSS1 and ADSS2 genes and comparatively analyzed their sequence, chromosome mapping, mRNA distribution and subcellular localization. According to our results, the ADSS1 gene was predominantly expressed in the striated muscle tissues, while ADSS2 gene distributed widely in all the tissues detected. Additionally, ADSS1 gene was up regulated significantly along with porcine muscle growth, and ADSS2 gene expression was more constant during the muscle development. Porcine ADSS1 gene was assigned to SSC7q and the linked marker was SSC12B09, ADSS2 gene was mapped on SSC10p and the linked marker was SW497, and porcine ADSS2 protein was subcellular localized in mitochondria. Moreover, we found that one single nucleotide polymorphism (SNP, T/C(70)) in the ninth intron of ADSS2 gene was significantly associated with average daily gain trait (ADG, P<0.05) and loin muscle area trait (P<0.05). PMID- 17347009 TI - Combining immunological and molecular data to assess phylogenetic relations of some Greek Podarcis species. AB - Most recent molecular studies revealed the phylogeny of Greek Podarcis species, which for years remained elusive, due to discordant data produced from various chromosomal, complement fixation and protein studies. In this report, we analyzed cellular immune responses of spleen-derived lymphocytes from six allopatric Podarcis species encountered in Greece, by assessing two-way mixed lymphocyte reaction (MLR)-induced proliferation. On the basis of stimulation indices (S.I.) as determined from cultures set up from xenogeneic splenocytes coincubated in pairs, we generated a phylogenetic tree, fully consistent with the phylogenetic relationships of Podarcis as determined by parallel analyses based on partial mitochondrial (mt) DNA sequences. Although the exact mechanisms triggering lymphocyte responses in lizard two-way xenogeneic MLR are not fully understood, our results show the potential use of cell-mediated immune responses as an additional approach to mtDNA analysis, for species delimitation within specific lizard taxa. PMID- 17347010 TI - Assessment of hydration by means of bioelectrical impedance and arm muscle area during growth hormone (GH) replacement therapy: A prospective study of 130 GH deficient patients. AB - OBJECTIVE: Growth hormone (GH)-deficiency is associated with a reduced extracellular volume (ECV), whereas GH replacement may cause fluid retention. We have tested a simple method to assess hydration in GH-deficient patients (GHD) based on concomitant measurements of body resistance by bioelectrical impedance analysis (BIA), and arm muscle area (AMA). DESIGN: We prospectively followed 130 patients (54 females, 76 males) with adult-onset GHD before and during 1-5 years GH replacement therapy. METHODS: Concomitant measurements of body resistance and AMA were done on four occasions: before treatment, after one month and one year of treatment, and at the most recent visit. Based on normative data obtained in 142 women and 84 men an inverse relationship was documented between body resistance and AMA. Assuming that linear height and the concentration of electrolytes remain constant, body resistance at a given AMA will reflect specific hydration. RESULTS: In the patients a gender-specific inverse correlation between body resistance and AMA existed, which was different from the control group and changed during GH replacement. A deviation between predicted (based on normative data) and measured body resistance at a given AMA was recorded in the patients before and during therapy compatible with relative dehydration in the untreated state followed by an increase in hydration during therapy. CONCLUSIONS: Concomitant measurements of BIA and AMA in GHD patients may provide a non-invasive and simple means to estimate hydration before and during GH replacement. PMID- 17347011 TI - Increased serum concentration of IGFBP-4 and IGFBP-5 in healthy adults during one month's treatment with supraphysiological doses of growth hormone. AB - OBJECTIVES: To study the effects on insulin-like growth factor binding proteins (IGFBP)-4 and -5 after one month's treatment with supraphysiological doses of growth hormone (GH) in healthy, active young adults with a normal GH-IGF-I axis. Furthermore, the possible use of IGFBP-4 and IGFBP-5 as markers of GH doping is discussed. DESIGN: Thirty healthy, physically active volunteers (15 men and 15 women), mean age 25.9 years (range 18-35), participated in this randomized, double-blind, placebo-controlled, parallel study with three groups (n=10; 5 men and 5 women in each group). The groups comprised the following: placebo, GH 0.1IU/kg/day [0.033mg/kg/day] and GH 0.2IU/kg/day [0.067mg/kg/day]. RESULTS: Baseline levels of IGFBP-4 were higher (+20%), while IGFBP-5 levels were lower ( 37%) in women than in men. IGFBP-5 levels were positively correlated to age, but no significant correlation was found for IGFBP-4. In the pooled group with active GH treatment (n=20), both IGFBP-4 and IGFBP-5 levels were increased vs. the placebo group from day 14 until end of treatment [day 28, IGFBP-4 (+40%, p<0.01) and IGFBP-5 (+61%, p <0.001)]. After inclusion of serum IGF-I as a covariate in the linear regression analysis, the associations between GH treatment and the IGFBP-4 and IGFBP-5 levels were not significant. CONCLUSIONS: This study shows that the levels of IGFBP-4 and IGFBP-5 are affected by supraphysiological GH treatment given to young, healthy, physically active adults of both genders. The present study, including relatively few subjects, does not support that IGFBP-4 and IGFBP-5 can be used as IGF-I independent markers in a forthcoming method for detecting GH doping, although, further studies are needed to investigate the potential use of IGFBP-4 and IGFBP-5 as markers of GH doping. PMID- 17347012 TI - The Internet and the diabetic foot: quality of online information in French language. AB - The Internet has become a major source of health information for consumers. Nevertheless the quality of medical information varies widely and is generally poor. AIM: This study aimed to evaluate the quality of information delivered on French-speaking Internet about the diabetic foot. METHODS: Websites were selected using three popular search engines and introducing "foot+diabetes" and "foot+diabetic" as keywords. Two diabetologists independently evaluated the quality of information using a specially created scoring grid (range 0-52) based on acknowledged and published criteria with items relevant to general characteristics of the site and to information content. One hundred and twenty websites were selected but only 27 were included for analysis. RESULTS: Agreement between the two raters was close for global score and site content but lower for site characteristics. Averaged global score ranged from 8 to 44. Only five sites were assessed as very advisable with a score higher than 39; in contrast 18 sites were judged as not advisable at all (score lower than 26). CONCLUSION: This study, the first to be devoted to information about the diabetic foot on the Internet, clearly shows the variability and the general poor quality of information delivered by the great majority of French-speaking websites. Regulation organisms are urgently needed for checking and labelling public oriented health information in order to make the Internet a performing tool for patient information. PMID- 17347013 TI - Inhibition of leukotriene biosynthesis abrogates the host control of Mycobacterium tuberculosis. AB - Leukotrienes produced from arachidonic acid by the action of 5-lipoxygenase (5 LO) are classical mediators of inflammatory responses. Recently, it has been demonstrated that leukotrienes also play an important role in host defense against microorganisms. In vitro studies have shown that leukotrienes augmented the anti-mycobacterial activity of neutrophils. In this study, we examined the role of leukotrienes in regulating host response and cytokine generation in a murine model of tuberculosis. Administration of the 5-LO pathway inhibitor MK 886, which reduced lung levels of both the leukotriene B(4) and the anti inflammatory substance lipoxin A(4) by approximately 50%, increased 60-day mortality from 14% to approximately 57% in Mycobacterium tuberculosis-infected mice, and increased lung bacterial burden by approximately 15-fold. Although MK 886-treated animals exhibited no reduction in pulmonary leukocyte accumulation, they did manifest reduced levels of nitric oxide generation and of the protective type 1 cytokines interleukin-12 and gamma interferon. Together our results demonstrate that 5-LO pathway product(s) - presumably leukotrienes - positively regulate protective Th1 responses against mycobacterial infection in vivo. Moreover, the immunosuppressive phenotype in infected mice observed with MK 886 is most consistent with inhibition of an activator (LTB(4)) rather than a suppressor (LXA(4)) of antimicrobial defense, suggesting the major effect of leukotrienes. PMID- 17347015 TI - Identification and characterization of onchoastacin, an astacin-like metalloproteinase from the filaria Onchocerca volvulus. AB - The tissue-invasive nematode Onchocerca volvulus causes skin and eye pathology in human onchocerciasis. While the adult females reside sessile in subcutaneous nodules, the microfilariae are abundantly released from the nodules, males and juvenile worms migrate through the host tissue. Matrix-degrading metallo- and serine proteinases have been detected in excretory-secretory worm products that may be essential for migration of the mobile stages. In this study, a 1713bp long cDNA encoding for a putative proteinase of O. volvulus has been isolated. The predicted protein sequence includes a signal peptide indicating secretion to the extracellular space, a propeptide, an astacin-like protease domain, an EGF-like and a CUB-domain, thereby identifying the protein as a member of the astacin family of zinc endopeptidases. Onchoastacin, Ov-AST-1, is most closely related to a subfamily comprising nematode astacins including Caenorhabditis and Ancylostoma. Ov-AST-1 was expressed as a recombinant protein in baculovirus infected insect cells and exhibited enzymatic activity. The exposure of onchoastacin to the host immune system is indicated by demonstration of IgG reacting with the recombinant Ov-AST-1 and with two peptides of the protein. Since a homologous metalloproteinase is part of a promising hookworm vaccine, Ov AST-1 may be a candidate for intervention strategies in filarial infections. PMID- 17347014 TI - Allelic variation in BTNL2 and susceptibility to tuberculosis in a South African population. AB - Tuberculosis and sarcoidosis show phenotypic features of granulomatous disease. The bacterium Mycobacterium tuberculosis can induce the expression of the sarcoidosis susceptibility gene BTNL2 in monocyte-derived macrophages. BTNL2 was therefore investigated as a candidate gene for tuberculosis in a case-control association study in the South African Coloured population. We sequenced the coding regions of BTNL2 to detect known and novel polymorphisms and genotyped 18 SNPs in 432 pulmonary tuberculosis cases and 482 controls. We did not find a significant association between the truncating rs2076530 SNP, previously associated with sarcoidosis, and tuberculosis. No association was found between any of the other SNPs studied and disease and none of the estimated haplotypes showed any association with TB. Comparative analyses with the South African data from this study and published data on German and American populations revealed that, for a segment of BTNL2, the admixed, but not stratified, South African population resembles the African-Americans more than white populations. PMID- 17347016 TI - Human immunodeficiency virus type 1 Vpr interacts with spliceosomal protein SAP145 to mediate cellular pre-mRNA splicing inhibition. AB - Vpr, an accessory gene product of human immunodeficiency virus type 1 (HIV-1), affects both viral and cellular proliferation by mediating long terminal repeat activation, cell cycle arrest at the G2 phase, and apoptosis. We previously found that Vpr plays a novel role as a regulator of pre-mRNA splicing both in vivo and in vitro. However, the cellular target of Vpr, as well as the mechanism of cellular pre-mRNA splicing inhibition by Vpr, is unknown. Here, we show clearly that Vpr inhibits the splicing of cellular pre-mRNA, such as beta-globin pre-mRNA and immunoglobulin (Ig) M pre-mRNA and that the third alpha-helical domain and arginine-rich region are important its ability to inhibit splicing. Additionally, using mutants with specific substitutions in two domains of Vpr, we demonstrated that the interaction between Vpr and SAP145, an essential splicing factor, was indispensable for splicing inhibition. Finally, co-immunoprecipitation and in vitro competitive binding assays indicated that Vpr associates with SAP145 and interferes with SAP145-SAP49 complex formation. Thus, these results suggest that cellular expression of Vpr may block spliceosome assembly by interfering with the function of the SAP145-SAP49 complex in host cells. PMID- 17347017 TI - Valuable lessons from SAPHO syndrome. PMID- 17347018 TI - Energetic balance in an ultrasonic reactor using focused or flat high frequency transducers. AB - In order to undertake irradiation of polymer blocks or films by ultrasound, this paper deals with the measurements of ultrasonic power and its distribution within the cell by several methods. The electric power measured at the transducer input is compared to the ultrasonic power input to the cell evaluated by calorimetry and radiation force measurement for different generator settings. Results obtained in the specific case of new transducer types (composites and focused composites i.e., HIFU: high intensity focused ultrasound) provide an opportunity to conduct a discussion about measurement methods. It has thus been confirmed that these measurement techniques can be applied to HIFU transducers. For all cases, results underlined the fact that measurement of radiation pressure for power evaluation is more adapted to low powers (<15 W) and that measurement by calorimetry is a valid technique for global energy measurements. Composites and monocomponent transducers were compared and it appears that the presence of an adaptation glass plate reduces the efficiency of the monocomponent transducers. The distribution of ultrasonic intensity is qualitatively depicted by sono chemiluminescence of luminol. Finally, the quantity of energy absorbed by samples placed in the sound field is determined and the temperature distribution monitored as a function of wall distance. This energetic balance allows us to understand the global behaviour of all experimental set-ups made up of a generator-transducer-liquid and sample. PMID- 17347019 TI - Effect of exposure parameters on cavitation induced by low-level dual-frequency ultrasound. AB - In order to quantify the effects of exposure parameters under therapeutic conditions such as sonodynamic therapy, it is necessary initially to evaluate the inertial cavitation activity in vitro. In this study, the dependence of cavitation activity induced by the low-level dual-frequency ultrasound irradiation on exposure parameters has been studied. Experiments were performed in the near 150 kHz and 1 MHz fields in the progressive wave mode. It has been shown that at constant ultrasound energy the fluorescence intensity for continuous sonication is higher than for pulsed mode. With increasing the duty cycle of pulsed field, the inertial cavitation activity is increased. The activity of cavitation produced by simultaneous combined sonication by two ultrasound fields is remarkably higher than the algebraic sum of effects produced by fields separately (p-value<0.05). This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is more effective in producing inertial cavitation activity at low-level intensity. Therefore, it is concluded that investigations in this combined ultrasound sonication can be useful in sonodynamic therapy for superficial tumors. PMID- 17347020 TI - Alleged rape--a case study illustrating potential difficulties in interpretation of ano-genital findings--a personal view. AB - In cases of alleged rape the complainant (or "complainer" in Scotland) may be in a position to identify the alleged assailant and as a result of the advances in forensic science the issue frequently relates to the question of consent. In addition to collection of relevant forensic samples, the forensic medical examiner (FME) is required to examine the complainer for evidence of recent injury and interpret the relevance of the clinical findings. In these specialised forensic cases while it is appropriate that the FME adopts an empathic approach it is essential that clinical objectivity is retained such that we may be in a position to provide an entirely impartial professional report which will assist in the investigation of the complaint. Irrespective of our involvement in these cases, whether at the request of the prosecution or the defence, it is essential to remember our position as independent forensic practitioners particularly when asked to offer an opinion on relevant clinical findings. This paper examines one case in detail and considers the elements of clinical examination; report writing; interpretation of injuries; comparing findings in alleged non-consensual and consensual intercourse; and finally the provision of appropriate medical opinions. PMID- 17347021 TI - How many parkinsonian patients are suitable candidates for deep brain stimulation of subthalamic nucleus? Results of a questionnaire. AB - We used a CAPSIT-based questionnaire to estimate the percentage of parkinsonian patients suitable for subthalamic nucleus (STN) deep brain stimulation (DBS) in a movement disorders clinic. We found that out of 641 consecutive PD patients only 1.6% fulfilled strict STN-DBS criteria. When we applied more flexible criteria, the percentage of eligibility increased to 4.5%. Most patients (60%) were ineligible because they did not satisfy multiple questionnaire items. Items related to disease severity were responsible for the largest number of exclusions. This knowledge will help make decisions on resource allocation in centres wishing to start DBS surgery. PMID- 17347022 TI - Both early and late cognitive dysfunction affects the electroencephalogram in Parkinson's disease. AB - We sought to define quantitative electroencephalographic (EEG) measures as biomarkers of both early and late cognitive decline in Parkinson's disease (PD). PD subjects classified as cognitively normal (PD-CogNL), mild cognitive impairment (PD-MCI), and dementia (PD-D) were studied. Cognitive status and neuropsychological testing was correlated with background rhythm and frequency band EEG power across five frequency bands. We conclude that global EEG measures have potential use as biomarkers in the study of both early and late cognitive deterioration in PD, including for evaluating its treatment. PD-MCI has mean quantitative EEG characteristics that represent an intermediate electrophysiological state between PD-CogNL and PD-D. PMID- 17347024 TI - The relevance of cytokines for development of protective immunity and rational design of vaccines. AB - Cytokines are key regulators of the immune system that shape innate and adaptive immune responses. An adequate balance of the cytokine environment is critical to achieve protective immunity and to avoid immunopathology. Present knowledge allows a deeper understanding of the cytokine network and their sometimes conflicting roles in the development of immune responses, as well as their relevance in the establishment and maintenance of immunological memory. New insights have been gained into the role of different T cell subsets for protection against infection or tumor growth. The incorporation of cytokines as molecular adjuvants in vaccines has been attempted to strengthen vaccine-induced immune responses, and as a rational approach to modulate cytokine milieu in vivo and tailor host immunity for specific situations. These approaches have been tried in experimental models and veterinary species, and a few of them have entered into clinical trials. However, manipulating the cytokine network to modulate immune responses is not a simple task, because cytokine functions are complex and the final effects on the immune response will depend on timing and length of exposure, cell(s) targeted and other cytokines present in the same microenvironment. Here, we will review our present understanding on the role of cytokines in the development of effector and memory T cell responses. Also the potential use of cytokines as molecular adjuvant for vaccines against infectious diseases and cancer will be revised. PMID- 17347025 TI - Cytokines and the immune-neuroendocrine network: What did we learn from infection and autoimmunity? AB - The initial view of the neuroendocrine-immune communication as the brake of immune activation is changing. Recent evidence suggests that the optimization of the body's overall response to infection could be actually the role of the immune endocrine network. In gradually more complex organisms, the multiplicity of host pathogen interfaces forced the development of efficient and protective responses. Molecules such as cytokines and Toll-like receptors (TLRs) are distributed both in the periphery and in the brain to participate in a coordinated adaptive function. When sustained release of inflammatory mediators occurs, as in autoimmune diseases, undesirable pathological consequences become evident with different manifestations and outcomes. Clearly, organisms are not well adapted to that disregulated condition yet, suggesting that additional partners within neuroendocrine-immune interactions might emerge from the evolutionary road. PMID- 17347026 TI - Motion, emotion and empathy in esthetic experience. AB - The implications of the discovery of mirroring mechanisms and embodied simulation for empathetic responses to images in general, and to works of visual art in particular, have not yet been assessed. Here, we address this issue and we challenge the primacy of cognition in responses to art. We propose that a crucial element of esthetic response consists of the activation of embodied mechanisms encompassing the simulation of actions, emotions and corporeal sensation, and that these mechanisms are universal. This basic level of reaction to images is essential to understanding the effectiveness both of everyday images and of works of art. Historical, cultural and other contextual factors do not preclude the importance of considering the neural processes that arise in the empathetic understanding of visual artworks. PMID- 17347027 TI - The default self: feeling good or being right? AB - The medial prefrontal cortex exhibits a higher resting metabolic rate than many other brain regions. This physiological default mode might support a psychological default state of chronic self-evaluation that helps people consider their strengths and weaknesses when planning future actions. However, a recent imaging study that relates medial prefrontal cortex activity to self-evaluation raises new questions about whether the psychological default mode of self evaluation is best characterized by accurate self-evaluations or by feeling good about yourself. PMID- 17347028 TI - Macro, micro and nano domains in the membrane of parasitic protozoa. AB - The structural organization of the plasma membrane of eukaryotic cells is briefly revised taking into consideration the organization of proteins and lipids and the concept of microdomains, lipid rafts and detergent resistant membranes. The biochemical data available concerning the presence of microdomains in parasitic protozoa is reviewed and emphasis is given on the identification of special domains recognized by morphological approaches, especially with the use of the freeze-fracture technique. PMID- 17347029 TI - Allelic diversity in the merozoite surface protein 1 gene of Plasmodium falciparum on Palawan Island, the Philippines. AB - Allelic diversity of the Plasmodium falciparum merozoite surface protein 1 gene (msp1) is mainly generated by meiotic recombination at the mosquito stage. We investigated recombination-based allelic diversity of msp1 in a P. falciparum population from Palawan Island, the Philippines, where malaria transmission is moderate. We identified the 5' recombinant types, 3' sequence types and msp1 haplotypes (unique combinations of 5' recombinant type and 3' sequence type), and compared them with those of P. falciparum from the Solomon Islands, where malaria transmission is high. The mean number of 5' recombinant types per patient in Palawan was 1.44, which is comparable to the number for the Solomon Islands (1.41). The Palawan parasite population had 15 msp1 haplotypes, whereas the Solomon Islands population had only 8 haplotypes. The Palawan population showed strong linkage disequilibrium between polymorphic blocks/sites within msp1, which is comparable to the results for the Solomon Islands. These findings support our hypothesis that the extent of allelic diversity of msp1 is determined not only by the transmission intensity but also by the number of msp1 alleles prevalent in the local parasite population and the extent of mixed-allele infections. Contribution of a high prevalence of the chloroquine (CQ)-sensitive allele of P. falciparum CQ resistance transporter (pfcrt) to the relatively high msp1 diversity in the Palawan population is discussed. PMID- 17347030 TI - Raman spectroscopic analysis of Mexican natural artists' materials. AB - This work represents the Raman spectra of 15 natural artists' materials that were obtained from local market in Mexico. Some of these products are not endemic to the region, but are often used in local conservation practice. Other materials are of local origin and have been used for centuries by local craftsmen. The Raman spectra that are reported here are: Chia oil, linseed oil, Campeche wax, beeswax, white copal, dammar, colophony, mastic, pixoy, chapopote, chucum, aje gum, gutta gum, peach gum and gum Arabic. The sample of pixoy was mixed with TiO(2), although it was not clear whether this was done intentionally or not. The Raman spectrum of chapopote, the local name for bitumen, contained features of carbonaceous and terpenoid matter. The Raman spectra of chapopote and chucum suffered severely from fluorescence, resulting in noisy Raman spectra. Aje gum and gutta gum are not gums, since they are resinous (terpenoid) in nature. Aje is a rare animal resin originating from Coccus axin. PMID- 17347031 TI - Spectroscopic and electrochemical investigation with coordination stabilities: mononuclear manganese(II) complexes derived from different constituents macrocyclic ligands. AB - Since the manganese(II) complexes are known as having a high degree of stability, some of them may be able to play a very important role in biosystems. We prepared manganese(II) complexes with different chromospheres containing macrocyclic ligands bearing N, S and O like functional donor atoms in order to obtain different models of compounds. So these new manganese(II) complexes were derived from macrocyclic ligands by chelating them with metal ions. Thus, two macrocyclic ligands, L(1): 2,4-diphenyl-1,5-diaza-8,12-dioxo-6,7:13,14-dibenzocyclo tetradeca 1,4-diene[N(2)O(2)]ane; L(2): 2,4,9,11-tetraphenyl-6,13-dimethyl-1,5,8,12 traazacyclotertr-adeca-1,4,8,11-tetraene[N(4)]ane; and two more different form first one viz.-L(3): 1,7-diaza-4-monothia-10,14-dioxo-8,9:15,16 cyclohexadecane[N(2)O(2)S]ane and L(4): 4,13-diaoxa-1,7,10,16 hexazacyclooctadecane[N(4)O(2)]ane were prepared and their capacity to retain the manganese(II) ion in solid as well as aqueous solution was determined from various physiochemical techniques viz: characterized by elemental analyses, molar conductance measurements, magnetic susceptibility measurements, mass, IR, electronic, ESR spectral studies and cyclic voltammetric measurements. PMID- 17347033 TI - Response of the oxygen uptake efficiency slope to exercise training in patients with chronic heart failure. AB - BACKGROUND: The oxygen uptake efficiency slope (OUES) is a new exercise parameter that provides prognostic power in patients with CHF. Little is known about the effects of exercise training (ET) on OUES. AIM: To describe the response of OUES to 6 months of ET in CHF patients and compare its evolution to that of other exercise variables. METHODS: 35 patients with CHF (NYHA II-III, age 54+/-9y, LVEF 31+/-10%) performed 3 maximal exercise tests, i.e. at the start, middle and end of a 6 month ET program. OUES, PeakVO(2), ventilatory anaerobic threshold (VAT) and slope VE/VCO(2) were determined. RESULTS: OUES, peakVO(2), VAT, slope VE/VCO(2), peak Watt, 6MWT and NYHA-class improved during the first part of the ET period (p<0.05). Only VAT, peak Watt and 6MWT continued to improve during the second part of the ET period (p<0.05) Improvements in OUES correlated better with improvements in peakVO(2) (r=0.77, p<0.001), than changes in other prognostic variables. DISCUSSION: OUES improves significantly after 6 months of ET. Changes in peakVO(2) correlate best with changes in OUES. OUES is sensitive to ET and can be used to evaluate the progression of exercise capacity in CHF patients. PMID- 17347032 TI - Differences in cell morphology, lipid and apo B secretory capacity in caco-2 cells following long term treatment with saturated and monounsaturated fatty acids. AB - The suitability of the caco-2 cell line as a model for studying the long term impact of dietary fatty acids on intestinal lipid handling and chylomicron production was examined. Chronic supplementation of caco-2 cells with palmitic acid (PA) resulted in a lower triacylglycerol secretion than oleic acid (OA). This was coupled with a detrimental effect of PA, but not OA, on transepithelial electrical resistance (TER) measurements, suggesting a loss of structural integrity across the cell monolayer. Addition of OA reversed the adverse effects of PA and stearic acid on TER and increased the ability of cells to synthesise and accumulate lipid, but did not normalise the secretion of lipids by caco-2 cells. Increasing amounts of OA and decreasing amounts of PA in the incubation media markedly improved the ability of cells to synthesise apolipoprotein B and secrete lipids. Real time RT-PCR revealed a down regulation of genes involved in lipoprotein synthesis following PA than OA. Electron microscopy showed adverse effects of PA on cellular morphology consistent with immature enterocytes such as stunted microvilli and poor tight junction formation. In conclusion, previously reported differences in lipoprotein secretion by caco-2 cells supplemented with saturated fatty acids (SFA) and OA may partly reflect early cytotoxic effects of SFA on cellular integrity and function. PMID- 17347035 TI - Caregiver burden in partners of Heart Failure patients; limited influence of disease severity. AB - BACKGROUND: In complying with required life style changes Heart Failure (HF) patients often depend on their partners. However providing care may cause burden and affect the health of these partners. The aim of this study was to investigate determinants of caregiver burden in order to identify caregivers who are at risk. METHODS: Using a cross-sectional design, caregiver burden and potential determinants were measured in partners of HF patients. Demographic and clinical data were assessed in HF patients, partners completed questionnaires on caregiver burden (the Caregiver Reaction Assessment, CRA), caregiving tasks performed, physical and mental health status and quality of the marital relationship. RESULTS: In total 357 partners (75% female, mean age 67 years) participated. The physical health status of HF patients was only significantly associated with two domains of caregiver burden, 'disruption of daily schedule' (p<0.01) and 'loss of physical strength' (p<0.01). No associations were found with age, co-morbidity and LVEF. All domains of the CRA were mainly associated with the partner's own mental health (p<0.01) and with providing personal care to HF patients (p<0.01). Gender differences were only found with regard to the domain of 'feeling a lack of family support'. CONCLUSION: The assessment of caregiver burden should focus on the mental strength of partners. Furthermore when assistance in personal care is needed, additional support, either informal or professional, may be indicated. PMID- 17347034 TI - Alteration of myocardial sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+ exchanger expression in human left ventricular volume overload. AB - BACKGROUND: Reduced myocardial contractility is often attributed to altered Ca(2+) transients and expression of Ca(2+)-ATPase of the SR (SERCA) and Na+/Ca(2+)exchanger (NCX) genes. AIMS: To assess myocardial expression of SERCA and NCX protein levels in left ventricular (LV) remodelling due to chronic severe mitral regurgitation (MR). METHODS: Myocardial expression of SERCA/NCX in biopsy specimens obtained during mitral surgery was assessed in 36 MR patients with LV remodelling and plasma neurohumoral/cytokine activation and in four non-failing hearts (NFH). RESULTS: Myocardial protein levels of SERCA were significantly (20%) lower in the MR group than in NFH group (p=0.016). No significant changes in NCX were observed. However, a lack of homogeneity with regard to SERCA/NCX proteins was observed. Moreover, SERCA was negatively correlated with BNP (r= 0.49, p=0.02), TNFalpha (r=-0.68, p=0.0005) and IL-6 (r=-0.52, p=0.02), whereas NCX was only negatively correlated with TNFalpha (r=-0.62, p=0.002). CONCLUSIONS: MR patients showed wide variations in SERCA/NCX protein expression. Myocardial protein levels of SERCA were significantly lower in the MR population. Moreover, a correlation between BNP, cytokines (IL-6, TNFalpha) and the expression of SERCA/NCX proteins was observed. PMID- 17347036 TI - NT-proBNP correlates with right heart haemodynamic parameters and volumes in patients with atrial septal defects. AB - BACKGROUND: To investigate the role of N-terminal pro-BNP (NT-proBNP) for the estimation of right heart failure and pulmonary pressure in patients with atrial septal defects (ASD) before and after percutaneous defect closure. METHODS: We performed correlation analysis for NT-proBNP and right ventricular systolic pressure (RVSP) as well as right ventricular enddiastolic and endsystolic volume (RVEDV, RVESV) determined by cardiac magnetic resonance imaging (MRI) before and up to one year following ASD closure. Additionally NT-proBNP concentrations were correlated with right atrial (RA) and RV enddiastolic pressure (RVEDP), ASD size and interatrial left-to-right shunt. RESULTS: Baseline RVSP was 33+/-8 mmHg, which decreased significantly during follow-up. Initially, NT-proBNP levels were 240+/-93 pg/ml. After closure, a reduction to 116+/-62 pg/ml was obvious (p<0.01). Baseline MRI showed enlarged RV volumes in all individuals. At six and twelve months follow-up a significant reduction of RVEDV and RVESV was apparent. A positive correlation was noted between RV volumes and NT-proBNP (r=0.65, p<0.05). Furthermore RA pressure, RVEDP, RVSP and left-to-right shunt significantly correlated to peptide levels. No correlation was seen between ASD size and NT-proBNP. CONCLUSION: NT-proBNP correlates to right ventricular dilatation, pulmonary pressure and left-to-right shunt in volume load of the right heart caused by an underlying ASD. PMID- 17347037 TI - Comparison of B-type natriuretic peptide assays for identifying heart failure in stable elderly patients with a clinical diagnosis of chronic obstructive pulmonary disease. AB - AIMS: To compare the ability of different B-type natriuretic peptide (BNP) assays to identify heart failure in stable elderly patients with a diagnosis of chronic obstructive pulmonary disease (COPD). METHODS: 200 patients aged >or=65 years with COPD according to their general practitioner and without known heart failure, underwent a diagnostic work-up. The final diagnosis of heart failure was established by a panel using the diagnostic principles of the European Society of Cardiology. All available diagnostic results, including echocardiography, but not BNP or NT-proBNP measurements, were used. The ability of different B-type natriuretic peptide assays to identify heart failure was estimated using the area under the receiver operating characteristic curves (ROC-area). RESULTS: The ROC areas did not differ significantly between the various assays of NT-proBNP and BNP, and ranged from 0.68 (95%CI 0.60-0.73) to 0.73 (95%CI 0.64-0.81). For NT proBNP the age- and gender-independent 'optimal' cut-point was 15 pmol/l (125 pg/ml) and for BNP 10 pmol/l (35 pg/ml). All assays were much better at excluding than detecting heart failure. CONCLUSIONS: All assays of B-type natriuretic peptide showed reasonable and comparable accuracy in recognising heart failure. At 'optimal' cut-points, all assays performed better at excluding than detecting new cases of heart failure in this population. PMID- 17347038 TI - Assessment of cardiac asynchrony by radionuclide phase analysis: correlation with ventricular function in patients with narrow or prolonged QRS interval. AB - BACKGROUND: Conflicting data exist on the relation between the synchronism of cardiac contraction and ventricular function. AIM AND METHODS: A resting radionuclide ventriculography (RNV) was performed in 380 consecutive patients to evaluate the relationship between the synchronism of cardiac contraction and ventricular function. RESULTS: A significant, non-linear, relation was found between LVEF and intra-ventricular asynchrony or QRS, but not between inter ventricular asynchrony and LVEF. A linear correlation was observed between QRS and intra-ventricular or inter-ventricular asynchrony. Intra-ventricular asynchrony was identified as the major, independent, determinant of LV function. With the increase in QRS duration, a decrease in LVEF (p<0.001), and a worsening of either intra-ventricular (p<0.001) or inter-ventricular synchronism (p<0.05), was documented. However, 48% of patients with QRS 120-150 ms had abnormal inter ventricular and 42% abnormal intra-ventricular synchronism, while 27% of patients with QRS>150 ms had normal inter-ventricular and 25% normal intra-ventricular synchronism. CONCLUSIONS: Intra-ventricular asynchrony was identified as the major determinant of ventricular dysfunction. A consistent proportion of patients had asynchrony despite preserved QRS duration or normal synchronism with a QRS>150 ms. Fourier phase analysis of RNV may detect asynchrony better than QRS. The role of RNV for detection of individual patients who may most benefit from resynchronization therapy requires additional investigations. PMID- 17347039 TI - Clinical diagnosis of left ventricular dilatation and dysfunction in the age of technology. AB - BACKGROUND: The diagnostic process has become increasingly dependent on instrumental and laboratory investigation. AIM: To evaluate the accuracy of symptoms and signs in identifying left ventricular (LV) dilatation and/or systolic dysfunction. METHODS: A group of 100 patients in stable clinical condition and scheduled for cardiac magnetic resonance imaging was prospectively examined by two cardiologists, who were unaware of the individual patient's condition. Patients were interviewed and underwent physical examination. RESULTS: Several symptoms and signs were associated with LV dilatation and systolic dysfunction at univariate analysis. Using multiple logistic regression, a mitral systolic murmur, a laterally displaced LV impulse, orthopnoea and hepatomegaly were all independent predictors of LV dilatation (end-diastolic volume >or=110 ml/m(2)) (p<0.0001) and LV dysfunction (ejection fraction <45%) (p<0.0001). The combination of the above variables correctly identified 79% of patients with LV dilatation (sensitivity 51%, specificity 92%), and 82% of patients with LV dysfunction (sensitivity 68%, specificity 90%). Considering LV dilatation and dysfunction, 77% of patients were correctly identified after history alone (kappa=0.13), 84% after LV impulse examination (kappa=0.55) and 86% after cardiac auscultation (kappa=0.58). CONCLUSION: Symptoms and signs predict LV dilatation and/or dysfunction with fair sensitivity and excellent specificity. PMID- 17347040 TI - Chronic sildenafil lowers transpulmonary gradient and improves cardiac output allowing successful heart transplantation. AB - INTRODUCTION: For patients undergoing heart transplantation, an elevated pulmonary vascular resistance (PVR) increases mortality in the early post-heart transplant period. This study aimed to assess the effects of chronic sildenafil administration on the PVR, transpulmonary gradient (TPG), and cardiac output (CO) in patients with heart failure awaiting heart transplantation. METHOD: The data from serial right heart catheterizations (RHC) of six patients were analyzed. All patients demonstrated a reaction to the vasodilators glyceryl trinitrate or inhaled iloprost at initial RHC before commencing sildenafil. A follow-up RHC was performed as required to guide management. RESULTS: The average total daily dose of sildenafil was 100 mg for a period of 68+/-58 days (4-145). The average TPG at baseline was 23.7 mmHg and fell in 4 of the 6 patients (67%) with an average reduction of 4.5+/-7.3 mmHg (-5 to 14). The average PVR at baseline was 571 dyn s cm(-5) and fell in 5 of 6 patients (83%), with an average reduction of 167+/-266 dyn s cm(-5) (74-518). The CO at baseline was 3.95 L/min and rose in 5 of 6 patients (83%) with an average improvement of 0.58 L/min (-1.1 to 1.3). The mean pulmonary capillary wedge pressure (MPCWP) at baseline was 26.3 mmHg and fell in 5 of 6 patients (83%) with an average fall of 5.5 mmHg (-1 to 17). Four of the six patients achieved a final TPG<15 mmHg, which we consider to be acceptable for orthotopic heart transplantation, average 11 mmHg (8 to 13). Three of these patients have already undergone successful, uncomplicated heart transplantation. CONCLUSION: Chronic sildenafil use is safe and effective in reducing an elevated TPG and PVR in patients with heart failure requiring heart transplantation and allows patients to be transplanted who may otherwise have been excluded because of pulmonary hypertension. PMID- 17347041 TI - Electromechanical effects of cardiac resynchronization therapy during rest and stress in patients with heart failure. AB - BACKGROUND: Haemodynamic and functional effects of cardiac resynchronization therapy (CRT) have been studied mostly at rest. CRT effects on left ventricular (LV) dyssynchrony and function during stress have not been evaluated in detail. AIMS: We studied the electromechanical effects of CRT at rest and during Dobutamine stress echocardiography (DSE), during active and withheld CRT. METHODS: Twenty-one responders to CRT (62+/-12 yr) were assessed by walking test, quality of life, and BNP with active CRT ("on") and 2 weeks after pacing withdrawal ("off"). DSE (10 microg/kg/min) was performed both at "on" and "off" to evaluate dyssynchrony parameters, systolic and diastolic function. RESULTS: At rest, CRT withdrawal was associated with an increased interventricular mechanical delay (IVMD, from 21+/-18 ms to 49+/-24 ms, p<0.001) and impaired intraventricular synchrony. There was a significant decrease in LV systolic function and LV filling time. Dobutamine infusion had no impact on inter- and intraventricular synchrony. During stress, there was an improvement in LV performance both at "on" and "off". However, LV dp/dt, aortic VTI, cardiac output, mean systolic peak velocities and LV filling time during dobutamine stress were significantly greater with CRT "on". CONCLUSION: In long-term responders, CRT improves LV performance both at rest and during dobutamine stress. This is attributable to an improvement in LV synchrony, which is maintained during stress. PMID- 17347042 TI - Human exposure to heavy metals in the vicinity of Portuguese solid waste incinerators--Part 2: biomonitoring of lead in maternal and umbilical cord blood. AB - As part of environmental health surveillance programs related to solid waste incinerators located near Lisbon and on Madeira Island, human biomonitoring projects have been implemented in Portugal, some of them focused on cross sectional surveys of heavy metals in blood. One of the general aims of these programs is to provide Portuguese data on the extent and pattern of human exposure to the pollutants potentially released in the stack gases from the incinerators, namely heavy metals. The present investigation reports information specifically on blood lead levels of newborn-mother pairs living in the vicinity of the incinerators under study, as well as of statistically similar participants living outside the exposed area. For Lisbon, lead levels determined at the baseline period (T0), as well as three subsequent evaluations of potential specific impacts of the incinerator (T1, T2 and T3) are described in order to investigate spatial and temporal trends of human exposure to lead. Available data for Madeira, namely lead levels in blood from the study population before the incinerator started operation, is also described. For Lisbon, analyses showed a statistically significant decrease of lead concentrations in maternal (p<0.001) and umbilical cord blood (p<0.001) during the whole monitoring period. Practically "overt" transplacental exposure to lead was observed only in the Lisbon biomonitoring project and for some cross-sectional surveys. Baseline levels for Madeira were the lowest found in all observations already performed in both programs (maternal and umbilical cord mean lead levels of 0.4 microg/dl and 0.3 microg/dl, respectively). No statistical associations have been found between lead levels in blood and age neither for global populations from Lisbon and Madeira nor for specific groups included in the different observational periods. PMID- 17347043 TI - Twenty years of the German Environmental Survey (GerES): human biomonitoring- temporal and spatial (West Germany/East Germany) differences in population exposure. AB - The German Environmental Surveys (GerESs) are nationwide population studies, which have repeatedly been carried out in Germany since the mid-1980s. The subjects were representatively selected from the regional registration offices with regard to age, gender and community size. The first survey for adults (GerES I) was carried out in 1985/1986 (West Germany) followed by GerES IIa in 1990/1991 (West Germany) and GerES IIb in 1991/1992 (East Germany). In GerES II children were also included to some extent. In 1998, the third GerES for adults was conducted in both parts of Germany (GerES III). The current survey 2003/2006 (GerES IV) is focussing exclusively on children. A 1-year pilot study was conducted in 2001-2002 to collect information on parameters influencing the response rate and to test the suitability of the different instruments intended to be used for the main study. The main goal of the surveys is to analyse and document the extent, distribution and determinants of exposure to environmental pollutants of the German general population. Three main instruments of investigation were comprised in GerES: human biomonitoring (HBM), monitoring of the domestic environment, and collecting information on exposure pathways and living conditions via questionnaires. This paper is focussed on the general design of the GerESs, the trend over time and spatial differences (West Germany and East Germany) for HBM data on arsenic, cadmium, lead, mercury, pentachlorophenol (PCP), and polycyclic aromatic hydrocarbons (PAH). These substances have been determined in blood and/or morning urine of adults and children. All GerESs have been conducted in close connection with the National Health Interview and Examination Surveys performed by the Robert Koch-Institute, Berlin. PMID- 17347044 TI - Human biomonitoring studies in North Rhine-Westphalia, Germany. AB - The areas along the rivers Rhine, Ruhr and Wupper in North Rhine-Westphalia (NRW), Germany, represent the largest urban and industrial agglomeration in Europe with about 10 million inhabitants. Human biomonitoring (HBM) studies have been conducted in these areas since more than 30 years, mainly designed to evaluate internal exposure to air pollutants. Recent studies were focussed on residents living near industrial sources. The contaminants studied comprise heavy metals, metabolites of polycyclic aromatic hydrocarbons (PAH), persistent organic pollutants (POPs), volatile organic compounds (VOC), and markers of DNA exposure. Study groups were mainly children and elderly subjects. Human milk, blood, urine, teeth, hair and nails were investigated. Time trend analyses demonstrate a significant decline of exposure to many contaminants such as POPs and heavy metals. More recent studies suggest that there still is an increased internal exposure to metals, PAH and DNA damaging agents in children and women living very close to industrial sources. PMID- 17347045 TI - Anatomical exposure of ventricular septal defect. AB - The ventricular septal defect approached through the right atrium is associated with inadequate exposure and thus difficulty in its closure. The retraction, to expose the defect, leads to distortion of anatomy and a limitation of space to operate. We propose a simple procedure of retracting sutures to expose the defect without this limitation. PMID- 17347046 TI - Collateral circulation in native coarctation of the aorta--a new clinical sign? PMID- 17347049 TI - Risk factors for postoperative pulmonary complications in coronary artery bypass graft surgery patients. AB - BACKGROUND: Despite numerous advances in anesthesia, surgical techniques, and postoperative care for coronary artery bypass graft (CABG) surgery, postoperative pulmonary complications (PPCs) still account for postoperative morbidity. OBJECTIVE: To determine current risk factors for PPCs in CABG surgery patients. METHODS: A retrospective cohort design was used. Health records were reviewed for patients (n=315) who had CABG surgery at a large quaternary healthcare center over a 4 month period. Pre-, peri-, and postoperative risk factors for PPCs were recorded as binary variables. Data were further assessed according to PPCs and non-PPCs using logistic regression models. RESULTS: PPCs occurred in 99.4% of this CABG surgical cohort. Atelectasis, pleural effusion, atelectasis with pleural effusion, and pneumonia were the most frequent PPCs post CABG surgery. Age >65 years, diabetes, and ASA classification >3 were found to be related to the presence of atelectasis. No significant risk factors were related to the development of pleural effusion or atelectasis with pleural effusion. Postoperative pneumonia was associated with previous myocardial infarction, ventilation >10 h, and hospital stay >5 days. History of bronchitis and COPD were related to postoperative pneumothorax; history of heart failure, COPD, and other lung diseases were related to postoperative pulmonary edema. CONCLUSION: These findings contribute to the understanding of PPCs in post-CABG surgery patients and assist in identification of patients at risk for developing PPCs. PMID- 17347050 TI - Asymptomatic bacteriuria in pregnancy. AB - Screening for asymptomatic bacteriuria is a standard of obstetrical care and is included in most antenatal guidelines. There is good evidence that treatment of asymptomatic bacteriuria will decrease the incidence of pyelonephritis. All pregnant women should be screened for asymptomatic bacteriuria, and there are no new data that would indicate otherwise. Antibiotic treatment of asymptomatic bacteriuria is associated with a decrease in the incidence of preterm delivery or low birth weight, but the methodological quality of the studies means any conclusion about the strength of this association needs to be drawn cautiously. A better understanding of the mechanism by which treatment of asymptomatic bacteriuria could prevent preterm delivery is needed. While several rapid screening tests have been evaluated, none perform adequately to replace urine culture for detecting asymptomatic bacteriuria. Until there are data from well designed trials that establish the optimal duration of therapy for asymptomatic bacteriuria, standard treatment courses are recommended. PMID- 17347051 TI - Multiple cardiac metastases from a malignant melanoma. AB - Metastatic tumors in the pericardium or the heart are more common than primary tumors and their incidence has increased during the last decades due to the prolonged survival of patients with cancer and the increased prevalence of the disease in the general population. We present the case of a 36-year-old patient admitted to our hospital due to fatigue, dyspnea, and episodes of dizziness and fainting during the last month. He had a history of a malignant skin melanoma surgically removed 4 years ago. The echo study identified multiple metastases in the heart involving the pericardium, the myocardium and the right atrium, where the tumor was mobile creating mechanical tricuspid valve stenosis. Malignant metastasis was confirmed by pericardiocentesis and, although treatment with chemotherapy was promptly initiated, the patient died 4 months later. Despite the difficulty in clinical diagnosis of cardiac melanoma, early detection has important therapeutic and prognostic implications. Echocardiography is the most common diagnostic modality and transesophageal approach may be the technique of choice to image intracardiac metastatic tumors. PMID- 17347052 TI - Development and psychometric properties of the Thinking about Epilepsy questionnaire assessing children's knowledge and attitudes about epilepsy. AB - OBJECTIVE: Epilepsy is the most common neurological disorder in the world, yet it is still widely misunderstood. A lack of knowledge and negative attitudes about epilepsy are largely blamed for the stigma felt by people with epilepsy and their families. Recent calls for research into stigma have been made by the World Health Organization and international epilepsy organizations. Our objective is to describe the development, structure, and psychometric properties of the Thinking about Epilepsy questionnaire. METHODS: A 36-item questionnaire was designed to assess Grade 5 (ages 9-11) students' knowledge of and attitudes about epilepsy and to evaluate changes in knowledge and attitudes following an epilepsy education program. The questionnaire contains 18 knowledge, 10 attitude, and 8 demographic questions. RESULTS: Psychometric properties of the Thinking about Epilepsy questionnaire were ascertained using data from 783 Grade 5 students. Three items (one knowledge item and two attitude items) were removed prior to the factor analysis due to their low extraction communalities. Factor analysis revealed a bidimensional structure (knowledge and attitudes) with five knowledge factors and two attitude factors. The questionnaire was found to have good internal consistency reliability (Cronbach's alpha=0.74 for knowledge and 0.82 for attitudes). Both the knowledge and attitude measures were deemed to have acceptable face, content, and construct validity. CONCLUSION: The final 33-item Thinking about Epilepsy questionnaire demonstrates adequate reliability for the knowledge measure, good reliability for the attitude measure, and excellent validity for both measures. The Thinking about Epilepsy questionnaire offers a viable option for assessing elementary school students' knowledge and attitudes regarding epilepsy in general or in conjunction with its affiliated Thinking about Epilepsy education program. PMID- 17347053 TI - Psychiatric disorders in juvenile myoclonic epilepsy: a controlled study of 100 patients. AB - In this controlled study we evaluated the frequency of psychiatric disorders (PDs) in 100 patients with juvenile myoclonic epilepsy (JME) and compared it with that of 100 healthy controls matched with respect to age, gender, schooling, and socioeconomic status. Our aim was to quantify the frequency of PDs and evaluate the relationship between PDs and factors related to epilepsy. Subjects were evaluated with the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I) and Axis II disorders (SCID-II). Patients with JME presented with significantly more PDs (P<0.01) and psychosocial problems (P<0.01) than the controls. PDs were diagnosed in 49 patients with JME. Anxiety and mood disorders, present in 23 and 19 patients, respectively, were the most frequently observed. Twenty patients fulfilled criteria for personality disorders; 17 (85%) patients had cluster B personalities comprising the behavioral characteristics impulsivity, humor reactivity, emotional instability, and difficulty in accepting social rules, similar to those cited in the earliest mentioned description of this syndrome. PDs were more frequently observed in patients with higher seizure frequency (P<0.05). PMID- 17347054 TI - Landau-Kleffner syndrome with lateral temporal focal cortical dysplasia and mesial temporal sclerosis: a 30-year follow-up. AB - A 39-year-old man, who presented at age 312 with Landau-Kleffner syndrome, had persisting oral and written language deficits into adulthood. Seizures were easily controlled in childhood, but reemerged in adulthood as medication refractory complex partial seizures. Abnormal T2 signal hyperintensity was seen in the left mesial temporal area on brain MRI. Later, left temporal lobectomy revealed focal cortical dysplasia in the lateral temporal neocortex and gliosis plus neuronal loss in the hippocampus. This case suggests that focal cortical microdysgenesis may be a cause of the Landau-Kleffner syndrome. Persistent seizures in this illustrative case may have led to the evolution of dual-temporal lobe pathology with mesial temporal sclerosis. PMID- 17347055 TI - Effects of Triclosan on Mytilus galloprovincialis hemocyte function and digestive gland enzyme activities: possible modes of action on non target organisms. AB - Pharmaceuticals and Personal Care Products (PPCPs) are a class of emerging environmental pollutants with the potential of affecting various aquatic organisms through unexpected modes of action. Triclosan (2,4,4'-trichloro-2' hydroxydiphenyl ether) (TCS), is a common antibacterial agent that is found in significant amounts in the aquatic environment. In this work, the possible effects and modes of action of TCS were investigated in the marine bivalve Mytilus galloprovincialis Lam. In mussel immune cells, the hemocytes, in vitro short-term exposure to TCS in the low microM range reduced lysosomal membrane stability (LMS) and induced extracellular release of lysosomal hydrolytic enzymes. The effects on LMS were mediated by activation of ERK MAPKs (Extracellularly Regulated Mitogen Activated Protein Kinases) and PKC (protein kinase C) alpha and betaII isoforms, as demonstrated by both specific kinase inhibitors and Western blotting with specific anti-phospho-antibodies. The effects of TCS were confirmed in vivo, in the hemocytes of mussels injected with different concentrations of TCS (corresponding to 0.29, 2.9 and 29 ng/g dry weight) and sampled at 24 h post-injection. The possible in vivo effects of TCS were also evaluated on the activity of different enzymes in the digestive gland, the tissue mainly involved in accumulation and metabolism of organic contaminants in mussels. Significant increases were observed in the activity of the glycolytic enzymes PFK (phosphofructokinase) and PK (pyruvate kinase), as well as of GST (GSH transferase) and GSR (GSSG reductase), whereas a decrease in catalase activity was observed. The results demonstrate that in mussels TCS can act on kinase-mediated cell signalling, lysosomal membranes and redox balance in different systems/organs. Although further studies are needed in order to evaluate possible consequences of environmental exposure to TCS on mussel health, the results represent the first data on the possible modes of action of this widespread antibacterial in aquatic invertebrates. PMID- 17347056 TI - Potential effects of PKC or protease inhibitors on acute pancreatitis-induced tissue injury in rats. AB - BACKGROUND: Acute pancreatitis (AP) is still one of the severe diseases, that cause the development of multiple organ dysfunction with a high mortality. Effective therapies for AP are still limited, mainly due to unclear mechanisms by which AP initiates both pancreatic and extrapancreatic organ injury. METHODS: Protease inhibitors (aprotinin, pefabloc, trypsin inhibitor) and PKC inhibitors (polymyxin B, staurosporine) were administrated 30 min before induction of AP in rats. To investigate the pancreatic, systemic and lung inflammatory response and injury, plasma IL-6 and IL-10, pancreatic and pulmonary myeloperoxidase (MPO) levels, pancreatic protease activity and phospholipase A(2) (PLA(2)) activity in ascites were measured 3 and 6 h after AP induction. RESULTS: Pretreatment with protease inhibitors significantly prevented from AP-increased plasma levels of IL 10, pancreatic and pulmonary levels of MPO, pancreatic protease activity and the catalytic activity of PLA(2) in ascites. PKC inhibitors significantly reduced pancreatic and pulmonary levels of MPO and pancreatic protease activity. CONCLUSION: Inhibition of proteases in AP may be helpful in ameliorating the inflammatory reaction in both pancreatic and extrapancreatic tissues, where neutrophil involvement may be regulated by PKC and proteases. PMID- 17347057 TI - Biopartitioning micellar chromatography: an alternative high-throughput method for assessing the ecotoxicity of anilines and phenols. AB - An investigation of the use of the chromatographic retention (log k) as an in vitro approach for modelling the toxicity to Fathead Minnows of anilines and phenols is developed. A data set of 65 compounds with available experimental toxicity data was used. Log k data at three pH values were used for the compounds classification and two groups or 'MODEs' were identified. For one 'MODE' a quantitative retention-activity relationship (QRAR) model was calculated. Finally, it was used to estimate the toxicity to Fathead minnows of anilines and phenols for which experimental data are not available. These estimations were compared to those obtained from another toxicity (to Tetrahymena pyriformis) data set and those estimated from a U.S. EPA QSAR approach (ECOSAR software) to decide on the toxicity level according to the Directive 3/21/EEC. PMID- 17347058 TI - The determination of potassium concentration in vitreous humor by low pressure ion chromatography and its application in the estimation of postmortem interval. AB - An analytical method was developed for the determination of potassium in vitreous humor by low pressure ion chromatography (LPIC). Experimental conditions for LPIC analysis were optimized. High sensitivity and selectivity were obtained using this method. The LOD and LOQ were 1 and 2 mmol l(-1), respectively. The linearity was demonstrated from 2 to 20 mmol l(-1). The intra- and inter-day precision (CV) based on three concentrations was less than 5.0%. It was a simple and fast method to measure potassium and was suitable for evaluating the postmortem interval (PMI) in relatively well-preserved bodies. Sixty-two samples from medical-legal autopsies with known PMI were analyzed. A linear correlation equation for potassium concentration in the vitreous humor and PMI was established: [K(+)]=0.1702PMI+5.5678, r=0.8692. PMID- 17347059 TI - Determination of 4-alkyl 2,5 dimethoxy-amphetamine derivatives by capillary electrophoresis with mass spectrometry detection from urine samples. AB - The methylenedioxy-derivatives of amphetamine represent the largest group of designer drugs. The 4-methyl (DOM), -ethyl (DOET) and -propyl (DOPR) derivatives of 2,5-dimethoxy-amphetamine (2,5-DMA) were found to possess quite similar serotonin receptor affinities [R.A. Glennon, D.L. Doot, R. Young, Pharmacol. Biochem. Behav. 14 (1981) 287.]. This paper describes a method to screen for and quantify DOM, DOET and DOPR in urine samples, using capillary electrophoresis coupled to electrospray ionisation-mass spectrometry (CE-ESI-MS). Prior to CE-MS analysis, a simple solid-phase extraction (SPE) was used for sample cleanup. The method was validated according to international guidelines. Data for accuracy and precision were within required limits. Calibration curves were generated ranging from 10 to 1000 ng/mL and correlation coefficients always exceeded 0.996. PMID- 17347060 TI - Inheritance of hyperbilirubinemia: evidence for a major autosomal recessive gene. AB - BACKGROUND AND AIM: To clarify the precise mode of inheritance of Gilbert syndrome, an unconjugated familial hyperbilirubinemia, where impaired bilirubin conjugation is caused by reduced UGT1A1 activity determined by a defective function of the A(TA)6TAA promoter region of the UGT1A1 gene. SUBJECTS AND METHODS: Serum bilirubin levels were measured in a large, homogeneous resident population from North-Eastern Italy, consisting of 1.639 males (age 44.5+/-13.9, range 18-89 years), and 1.420 females (age 45.1+/-15.0, range 18-85). In 112 nuclear families from hyperbilirubinemic probands living in the same area a complex segregation analysis was then performed. In both samples we carefully excluded potentially confounding factors of bilirubin levels (alcohol abuse, excessive cigarette smoking, drug consumption, overt haemolysis and liver disease). RESULTS: Mean serum bilirubin concentrations are higher in males than in females, showing fluctuations through the different age periods in males. Complex segregation results demonstrate that unconjugated hyperbilirubinemia exhibits a precise mode of inheritance in which a major recessive gene with a frequency of 0.45 is responsible for higher serum bilirubin values. CONCLUSIONS: This major recessive gene accounts only for a part of the serum bilirubin concentration, thus implying additional, environmental factors for the clinical appearance of GS. PMID- 17347061 TI - Beclomethasone dipropionate versus mesalazine in distal ulcerative colitis: a multicenter, randomized, double-blind study. AB - BACKGROUND: Topical beclomethasone diproprionate has shown efficacy in ulcerative colitis. AIM: To assess, in a multicenter, randomized, double-blind study, the tolerability and safety of topical beclomethasone diproprionate (3mg) enema and foam versus mesalazine (2g) enema and foam in mild-moderate distal ulcerative colitis. PATIENTS: In 15 referral gastrointestinal units, 99 patients with distal ulcerative colitis were enrolled. This number was lower than planned according to the statistical analysis, due to a low recruitment rate. METHODS: Patients were randomly assigned to random preparations (beclomethasone diproprionate enema, beclomethasone diproprionate foam, mesalazine enema, mesalazine foam) once nightly for 8 weeks, with clinical and endoscopical assessment (Disease Activity Index score) at baseline (T0), 4 (T4) and 8 weeks (T8). Results were expressed as median and range (95% confidence interval). The efficacy was assessed by comparing the Disease Activity Index value at T4 and T8 by using the Student's t test or the Wilcoxon-Mann-Whitney test. RESULTS: Efficacy was comparable in the beclomethasone diproprionate or mesalazine groups at both T4 and T8 (response at T4: beclomethasone diproprionate 78% [95% confidence interval 0.6-0.8] versus mesalazine 79% [95% confidence interval 0.6-0.8]; T8: beclomethasone diproprionate 84% [95% confidence interval 0.7-0.9] versus mesalazine 90% [95% confidence interval 0.7-1.0]; p=n.s.; remission at T4: beclomethasone diproprionate 24% [95% confidence interval 0.1-0.3] versus mesalazine 28% [95% confidence interval 0.1-0.3]; remission at T8: beclomethasone diproprionate 36% [95% confidence interval 0.2-0.5] versus mesalazine 52% [95% confidence interval 0.3-0.6]; p=n.s.). The Disease Activity Index lowered at T4 and T8 versus T0 in the four groups (T4 versus T0: beclomethasone diproprionate foam Disease Activity Index 2 versus 6 p<0.0001; beclomethasone diproprionate enema 4 versus 6, mesalazine enema 3 versus 6, mesalazine foam 3.5 versus 7, p<0.001 for all three groups; T8 versus T0: p<0.01). The Disease Activity Index lowered at T8 versus T4 in the beclomethasone diproprionate enema and foam (Disease Activity Index: 2 versus 4 and 1 versus 4, respectively; p<0.05) and in the mesalazine enema (Disease Activity Index: 1.5, range 0-4 versus 3, range 0-12; p<0.01), but not in the mesalazine foam group (Disease Activity Index: 1, range 0-9 versus 3.5, range 0-8; p=n.s.). The safety profile was favourable for all groups. CONCLUSIONS: Beclomethasone diproprionate and mesalazine enema and foam show a comparable tolerability and efficacy in mild active distal ulcerative colitis. PMID- 17347062 TI - Perinatal infection with Group B streptococci. AB - Group B streptococcus (GBS) is a major cause of severe bacterial infection in newborns. Early neonatal GBS infection can be prevented by identifying high-risk pregnancies and administering intrapartum antibiotics. In the USA, a screening strategy has been introduced resulting in a reduction in early-onset GBS infection, but no decrease in late-onset neonatal GBS disease has been noted. In many European countries, a risk-based strategy is recommended. Vaccination may, in the future, be an alternative in preventing GBS infection in newborns. PMID- 17347064 TI - Changes in micro-CT 3D bone parameters reflect effects of a potent cathepsin K inhibitor (SB-553484) on bone resorption and cortical bone formation in ovariectomized mice. AB - Cathepsin K is a cysteine proteinase that is highly expressed by osteoclasts and is being pursued as a potential drug target for the treatment of osteoporosis. We have reported that microcomputed tomography (micro-CT) analysis of bone microarchitecture may serve as a valuable tool for evaluating both antiresorptive and anabolic agents in ovariectomized (OVX) mice. The purpose of this study was to evaluate the effect of SB-553484, a novel cathepsin K inhibitor (human Ki,app=0.14 nM, mouse Ki,app=26 nM), on the OVX mice by micro-CT bone morphometric analysis. Seven weeks female BALB/c mice were OVX or sham-operated. OVX animals were treated with SB-553484 (30 mg/kg, sc) or Rolipram (10 mg/kg, po), a phosphodiesterase 4 inhibitor used as a positive bone anabolic agent, twice a day for 2 weeks. Both SB-553484 and Rolipram significantly prevented the decrease of trabecular bone volume as well as the deterioration of trabecular architecture in OVX mice. Interestingly, SB-553484 demonstrated a more pronounced effect in improvement of trabecular separation, number and connectivity, and a weaker effect in improvement of trabecular thickness compared to that of Rolipram. These differences indicate that SB-553484 mainly acted as an antiresorptive agent in OVX-induced loss of trabecular bone. On the other hand, SB-553484 significantly increased cortical bone volume and cortical thickness as well as Rolipram in OVX mice indicating an unexpected stimulatory effect of SB 553484 on cortical bone formation. These data suggest that targeting cathepsin K may prove therapeutically beneficial in the treatment of diseases with accelerated bone loss such as postmenopausal osteoporosis not only by inhibiting bone resorption but also by potentially stimulating cortical bone formation. PMID- 17347063 TI - A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density. AB - Early data suggest that an annual i.v. infusion of zoledronic acid (ZOL) might have therapeutic use in women with osteoporosis. In this randomized, double blind, double-dummy, multicenter, 24-week trial, we evaluated the onset of action of a single infusion of ZOL 5 mg (n=69) compared with weekly oral alendronate (ALN) 70 mg (n=59) in postmenopausal women with low bone mineral density (T score< or =-2 by DXA) as assessed by reductions in urine N-telopeptide of type I collagen (NTX) at week 1. The effects of these therapies on other markers of bone turnover, patient preference for once yearly i.v. vs. oral weekly treatment, and adverse events were also assessed. At week 1, ZOL 5 mg resulted in a significantly greater reduction in mean urine NTX from baseline than ALN 70 mg (P<0.0001). Significantly greater reduction in urine NTX and serum beta-C telopeptide of type I collagen (beta-CTX) were also observed in the ZOL 5 mg group at all post-baseline time points. Bone-specific alkaline phosphatase (BSAP) levels showed a more gradual reduction in both the ZOL 5 mg and ALN 70 mg groups, reaching premenopausal range by week 12. A comparable proportion of patients reported adverse events in each treatment group (ZOL 5 mg, 91.3%; ALN 70 mg, 86.4%). Transient, flu-like symptoms were the most common adverse events in the ZOL 5 mg group and resulted in a higher frequency of adverse events in this group during the first 3 days of treatment. After 3 days, adverse event rates were similar in the 2 groups. The majority of patients, including those experiencing flu-like symptoms, expressed a preference for annual i.v. therapy (66.4%) compared with weekly oral therapy (19.7%). We conclude that a single i.v. infusion of ZOL 5 mg reduced urine NTX levels more rapidly than weekly oral ALN 70 mg. The majority of study patients preferred an i.v. treatment regimen of ZOL 5 mg over weekly osteoporosis therapy with ALN 70 mg. PMID- 17347065 TI - [New COPE membership, missing points and friends]. PMID- 17347066 TI - The relation between aortic atherosclerosis and risk factors. AB - OBJECTIVE: To evaluate the impact of risk factors on atherosclerotic changes of aortic wall and valve in patients with and without non-familial hypercholesterolemia by transthoracic echocardiography. METHODS: One hundred and eleven patients with non-familial hypercholesterolemia and 112 control subjects were included in the study. Aortic wall and valve were evaluated by visual assessment of wall hyperechogenicity and measuring the valve thickness. Aortic diameters were obtained at the levels of annulus, sinus of Valsalva and at the supravalvular level in the parasternal long-axis view by M-Mode echocardiographic examination. The relationship between parameters of aortic atherosclerosis and risk factors was studied by multivariate logistic regression analysis, Pearson and Spearman correlation analyses. RESULTS: The prevalence of aortic wall hyperechogenicity was found to be higher in patients with hypercholesterolemia (84.7% vs 70.5%, p=0.01). The mean aortic root diameters at all levels of patients with hypercholesterolemia were found to be significantly smaller than in patients of the control group (3.1+/-0.3 mm vs 3.2+/-0.5 mm, p=0.02 for annulus level, 3.4+/-0.4 mm vs 3.5+/-0.4, p=0.004 mm for the level of sinus of Valsalva and 3.2+/-0.3 mm vs 3.4+/-0.5 mm, p<0.001 - supravalvular level), but no difference was noted regarding the aortic velocity and pressure gradient across the aortic valve. Multivariate stepwise logistic regression analysis showed that age (OR=1.1, CI - 1.02-1.09, p=0.002) and smoking (OR=2.2, CI - 1.06-4.58, p=0.04) were independent predictors of aortic valve thickness. Hypercholesterolemia was an independent predictor for aortic wall hyperechogenicity (OR=2.5, CI - 1.3-4.9, p=0.009) but not for valve thickness. CONCLUSIONS: Age, smoking and hypercholesterolemia are related to atherosclerotic involvement of aortic wall and valve. PMID- 17347067 TI - [The comparison of logistic regression model selection methods for the prediction of coronary artery disease]. AB - OBJECTIVE: In this study, logistic regression model selection methods were compared for the prediction of coronary artery disease (CAD). METHODS: Coronary artery disease data were taken from 237 consecutive people who had been applied to Inonu University Faculty of Medicine, Department of Cardiology. Logistic regression model selection methods were applied to CAD data containing continuous and discrete independent variables. Goodness of fit test was performed by Hosmer Lemeshow statistic. Likelihood-ratio statistic was used to compare the estimated models. RESULTS: Each of the logistic regression model selection methods had sensitivity, specificity and accuracy rates greater than 91.9%. Hosmer-Lemeshow statistic showed that the model selection methods were successful in the description of CAD data. Related factors with CAD were identified and the results were evaluated. CONCLUSION: Logistic regression model selection methods were very successful in the prediction of CAD. Stepwise model selection methods were better than Enter method based on Likelihood-ratio statistic for the prediction of CAD. Age, diabetes mellitus, hypertension, family history, smoking, low-density lipoprotein, triglyceride, stress and obesity variables may be used for the prediction of CAD. PMID- 17347068 TI - Myocardial bridge: a bridge to atherosclerosis. AB - OBJECTIVE: Myocardial bridge (MB) is a congenital anomaly characterized by narrowing during systole of some of the epicardial coronary arterial segments running in the myocardium. Although, it is considered as a benign anomaly, it may lead to such complications as acute myocardial infarction, ventricular tachycardia, syncope, atrioventricular block and sudden cardiac death. In this study, we aimed to investigate demographic, clinical and angiographic characteristics of the patients with MB found on coronary angiography. METHODS: The present study included 71 patients with MB found on coronary angiographies performed in our institution between January 1999 and September 2003. Based on the findings on angiography, the patients were subdivided into group A (n=41) and group B (n=30). The patients in the group A had no atherosclerotic lesion and the patients in the group B had coronary artery disease in addition to MB. Angiographic, demographic and clinical characteristics of both groups were compared. RESULTS: There were no differences between two groups in distribution of gender and risk factors of coronary artery disease whereas mean age of the patients in the group A was lower (47+/-5 years vs 55+/-11 years, p=0.01). Frequency of two or more risk factors for coronary artery disease in a particular patient was significantly higher in the group B (55% vs 30%, p=0.03). Myocardial bridge was located at proximal or mid segments of left anterior descending artery (LAD) in 40 patients whereas its presence in both LAD and right coronary artery was found only in one patient in group A. Mean bridging percent was 43+/-27% in group A. Localization of MB was LAD in 29 patients of group B. One patient with severe aortic valve stenosis in this group had MB at first septal branch. Mean bridging percent was 70+/-25% in group B, which was significantly higher than in group A (p<0.05). Atherosclerotic narrowing developed in only LAD in 14 patients, LAD and other vessels in 7 patients and in the vessels without MB in 9 patients. In patients with MB in LAD atherosclerotic narrowing of vessel developed proximally to the MB. Clinically, stable angina pectoris was seen more frequently in group A than group B (70% vs 35%, p=0.01), whereas the frequency of acute coronary syndrome was higher in group B (65% vs 30%, p=0.04). In regard to therapeutic approach, more patients in the group A received medical management (80% vs 50%, p=0.01), while more patients in the group B underwent surgical and percutaneous interventions (50% vs 18%, p=0.04). CONCLUSION: Myocardial bridge probability should be considered in young patients presenting with angina or if the same symptoms are persistent in the patients without more than one risk factor for coronary artery disease. Myocardial bridge may initiate the development of atherosclerotic lesion or may facilitate progression of atherosclerosis in the proximal segment of the vessel. The risk of acute coronary syndrome rises when atherosclerosis is superimposed on MB. Myocardial bridge should be considered in the young patients, presenting with angina or its equivalents without atherosclerotic lesions on coronary angiography. PMID- 17347069 TI - Myocardial bridge and atherosclerosis. PMID- 17347070 TI - [Relationship between the slow coronary flow and carotid artery intima-media thickness]. AB - OBJECTIVE: This study was planned to investigate the relationship between slow coronary flow and the carotid artery intima-media thickness (CIMT) which is an indicator of early atherosclerotic changes in vascular tree. METHODS: Consecutive patients (n=203) who were free of any coronary lesions in coronary angiograms were enrolled. The patients were assigned into slow flow (97) and normal flow (106) groups according to the corrected TIMI frame count (CTFC) of every three coronary arteries. Carotid artery intima-media thickness was measured via computer software regarding far-wall method in both common carotid arteries. Maximum and mean CIMT values were compared between the two groups. The accuracy of CIMT in the prediction of slow coronary flow was estimated using Receiver Operating Characteristic curve (ROC) analysis. RESULTS: Maximum and mean CIMT values were 0.814+/-0.106 mm and 0.668+/-0.080 mm for normal flow group and 0.966+/-0.133 mm, 0.780+/-0.105 mm for slow flow group, respectively (p<0.001). Using 0.861 as the cut-off value for maximum CIMT positive and negative predictive values of slow flow were 80.1% and 70.2% (area under the ROC curve=0.809; p<0.001; 95% CI 0.750-0.868). CONCLUSIONS: We find out that CIMT and CTFC are strongly correlated. This implies that slow coronary flow could be an early marker of subclinical atherosclerosis. So patients with slow flow should be followed-up prospectively for possibility of manifest atherosclerosis. PMID- 17347071 TI - [Relationship of the blood pressure's level and skinfold thickness]. AB - OBJECTIVE: Hypertension is an important problem of the public health. Insufficient education of the people along with insufficient physical examination also plays a role in the poor success of the diagnosis and treatment of the hypertension. We investigated whether the skinfold thickness has an importance in the prediction of blood pressure or not. METHODS: In Aydin City area 110 women and 100 men selected by randomized sampling method were included into our study. Body mass index, blood pressure and skinfold thickness were measured according to the international guidelines. RESULTS: There was a moderate correlation between the skinfold and body mass index (r= 0.494, p=0.000) and there was a mild correlation between the body mass index and systolic and diastolic blood pressures (r=0.225, p=0.000 and r=0.300, p=0.000, respectively). There was no correlation between the skinfold thickness and systolic and diastolic blood pressures (r=0.058, p=0.400 and r=0.090, p=0.194, respectively). CONCLUSION: It is concluded that body mass index, not skinfold thickness, can be used for the prediction of the blood pressure. Some other factors independent from the body mass index might be the determinants of the skinfold thickness. PMID- 17347072 TI - [Prospective validation in identical Turkish cohort of two metabolic syndrome definitions for predicting cardiometabolic risk and selection of most appropriate definition]. AB - OBJECTIVES: To investigate the relative values in the prediction of type 2 diabetes and coronary heart disease (CHD) by the metabolic syndrome (MS) as defined by the ATPIII and by its modification of the Turkish Adult Risk Factor Study (TEKHARF-def) and selection of most appropriate definition. METHODS: Prospective evaluation of 1683 men and 1718 women, aged > or =28 years participating in the TEKHARF study surveys 1997/98 and 2002/03 with a mean follow up of 5.9 years. The modification involved especially abdominal obesity (> or =95 cm in men, > or =91 cm in women). RESULTS: After exclusion of participants with diabetes at baseline and adjustment for sex and age, both MS definitions predicted the development of diabetes with virtually identical relative risks (RR) (ATPIII 2.85 [95%CI 2.14; 3.80]; TEKHARF 2.84 [95%CI 2.13; 3.81]. After similar exclusion and adjustments, both MS definitions predicted significantly the development of CHD with similar RRs (ATPIII 2.10 [95%CI 1.64; 2.68] in 36% of the cohort; TEKHARF-def 1.90 [95%CI 1.49; 2.43] in 39.6% of the cohort. For both outcomes, the TEKHARF-def provided higher predictive values in men, and (because of the high density lipoprotein (HDL)-cholesterol cutoff) the ATPIII definition in women. Absolute annual CHD risk in individuals with MS exceeded on average 2%, while age > or =50 years constituted the most appropriate indicator of further elevated risk in both genders. Most suitable modifications of the ATPIII definition are proved to be impaired fasting glucose (IFG) > or =100 mg/dl and in men > or =95 cm of waist circumference. Most CHD cases afflicting Turkish adults (namely 61% in men and 69% in women) originated from the latter definition of MS. CONCLUSIONS: In predicting diabetes and CHD risk, the TEKHARF-def MS is more valuable in men; the ATPIII definition modified for IFG (> or =100 mg/dl) should be adopted in women. In 2 out of every 3 cases, CHD originates from MS among Turks, and age > or =50 years is a good indicator of higher risk in both genders. PMID- 17347073 TI - [Abdominal obesity and cardiometabolic risk]. PMID- 17347074 TI - Effect of diltiazem and metoprolol on left atrial appendix functions in patients with nonvalvular chronic atrial fibrillation. AB - OBJECTIVES: Thrombo-embolic events are the important cause of mortality and morbidity in patients with chronic atrial fibrillation (CAF). The origin of thromboembolism is often the left atrial appendix (LAA). Flow rate velocity (FRV) inside the LAA is the major determinant of thrombus formation. The aim of our study was to investigate the effects of diltiazem and metoprolol used for ventricular rate control on FRV of the LAA in CAF patients and thus to evaluate the positive or negative effects of these two drugs on thromboembolic events. METHODS: Sixty-four patients were included in the study. All patients were suffering from CAF for more than a year. The patients were allocated to two groups according with agent used for rate control- metoprolol (Group 1; n=31) and diltiazem (Group 2; n=33). Transesophageal echocardiography was applied to all patients and LAA FRV was measured by a pulse wave Doppler in the 1/3 proximal portion of the LAA. The measurements were repeated after applying 5 mg metoprolol to Group 1 and 25 mg diltiazem to Group 2 via venous cannula. RESULTS: In Group 1 after metoprolol LAA flow velocity changed from 0.25 +/- 0.90 m/s to 0.25 +/- 0.10 m/s (p>0.05). In group 2 after diltiazem left atrial appendix FRV decreased from 0.21 +/- 0.9 m/s to 0.19 +/- 0.6 m/s (p>0.05). CONCLUSIONS: In patients with CAF metoprolol used for ventricular rate control had no effect on LAA flow velocity and the observed decrease in LAA flow rate velocity with intravenous diltiazem was insignificant. PMID- 17347075 TI - The effect of pharmacological agents on left atrial appendage function in patients with atrial fibrillation. PMID- 17347076 TI - Association of renal functional impairment and the severity of coronary artery disease. AB - OBJECTIVE: Cardiovascular diseases are the most common cause of death in patients with renal failure. Glomerular filtration rate (GFR) is used for the assessment of the renal functional status. In this study we aimed to examine the association between severity of coronary stenosis and renal function by quantifying the coronary lesions, angiographically and calculating the renal function with the use of GFR. METHODS: Forty-three patients with decreased renal function (calculated GFR<80 ml/min) with a mean age of 67.8+/-9.0 years and 49 patients without impaired renal function (calculated GFR>/=80 ml/min) with a mean age of 52.5+/-10.3 years were studied consecutively from March 2005 to September 2005. Glomerular filtration rate was calculated according to a given formula. All patients underwent selective coronary artery angiography and Gensini scoring system was used for the detection of severity of coronary atherosclerosis. RESULTS: In linear regression analysis, a negative correlation was found between renal function and the severity of coronary atherosclerosis (r=0.326, p=0.002). All patients were classified into quartiles of Gensini score level. In multivariate analysis, the multiple-adjusted odds ratio (OR) of the risk of decreased renal function was 0.99 (95% CI 0.24-4.15) for quartile 2, 4.38 (95% CI 1.11-17.20, p=0.03) for quartile 3, and 7.01 (95% CI 1.72-28.61, p=0.007) for quartile 4 of Gensini score level compared with the quartile 1. CONCLUSION: Coronary atherosclerosis quantified by Gensini score is significantly associated with the severity of decreased renal function and this association is independent of age and other cardiovascular risk factors. PMID- 17347077 TI - Coronary lesion characteristics in patients with impaired renal function. PMID- 17347078 TI - Simultaneous percutaneous atrial septal defect closure and percutaneous coronary intervention. AB - OBJECTIVE: To evaluate the possibility to perform both percutaneous coronary interventions (PCI) and atrial septal defect (ASD) transcatheter treatment during the same session. Transcatheter ASD closure is a well-established alternative to surgery and the treatment of choice for single vessel coronary artery disease (CAD) is accepted to be PCI. METHODS: From January 2000 to December 2005, 985 patients were referred to our center for ASD closure. One hundred thirty four patients (59 males, mean age 58 +/- 4 years, range 45-72 years) were included in a prospective protocol of ASD transcatheter closure and coronary angiography. RESULTS: In 7 patients we found a coronary artery disease. A combined single setting definitive percutaneous approach (ASD closure and PCI) was performed in 6 patients. The patient number 4 was judged unsuitable for PCI and then was referred for surgery. There was no acute intra-procedural complication in all patients; renal functions pre and post procedure showed no change despite the increase in the amount of contrast used. CONCLUSION: Our report showed the feasibility of both PCI and ASD transcatheter treatment during the same session. PMID- 17347079 TI - [Antithrombotic therapy in atrial fibrillation with ximelagatran: can it be an alternative to warfarin?]. AB - Nonvalvular atrial fibrillation is the most common cardiac arrhythmia associated with a substantial risk of thromboembolism and stroke. Despite numerous disadvantages that limit its efficacy and safety, warfarin is widely used in the prevention and treatment of thromboembolism related with atrial fibrillation. Ximelagatran, an oral direct thrombin inhibitor has the potential to be an alternative choice in the prevention and therapy of thromboembolism related with atrial fibrillation. Studies compared ximelagatran with warfarin in nonvalvular atrial fibrillation at risk for stroke showed that fixed dose oral ximelagatran is effective as adjusted dose warfarin in stroke prevention. Ximelagatran has numerous advantages over warfarin in clinical practice. Although it seems as a promising option for the prevention and therapy of thromboembolism, its safety and efficacy need to be determined definitely by further clinical trials. PMID- 17347080 TI - [Pre-hospital thrombolytic therapy]. AB - Reperfusion therapy with intravenous thrombolytic agents in acute ST-segment elevation myocardial infarction reduces the infarct size, preserves ventricular function, and therefore reduces mortality. Experimental and clinical studies also showed that time to successful reperfusion is a critical determinant of survival. In this paper the importance of very early (pre-hospital) thrombolysis, its comparison with percutaneous interventional therapy and the feasibility in Turkey are discussed. Although primary coronary interventions are preferred in patients with ST-segment elevation myocardial infarction intravenous, early bolus thrombolysis in the pre-hospital stage provides a therapeutic option as good as primary angioplasty. Until necessary policy and technical substructure are completed cardiology centers should apply the most suitable reperfusion strategy according with the guidelines, feasibilities and their experience. PMID- 17347081 TI - [The surgical treatment of atrial fibrillation]. AB - The surgical treatment of atrial fibrillation (AF) has entered a new era with the development of new tools and advanced techniques. The Maze III operation remains as the gold standard for the surgical treatment of AF. However new energy sources have been adopted for treating this arrhythmia in an effort to reduce the invasiveness and technical concerns with the original procedure. Success rates ranging between 70-98% have been reported using these new techniques. On the other hand, interventional cardiologists have further improved their techniques so that percutaneous techniques are competing with minimally invasive ablation techniques for the treatment of drug resistant and symptomatic lone AF. These developments have aroused the interest of cardiac surgeons in AF surgery and have found themselves a wide application. It has been estimated that thirty thousand patients have undergone surgical ablation for AF so far. Inevitably, procedure related complications have occurred and caused skepticism by some groups. However, surgical ablation has become a widely accepted treatment modality for AF patients undergoing concomitant cardiac surgery. The aim of this text is to make an overall review of the surgical treatment of AF and evaluate the current situation in view of the literature and the personal experience of the authors. PMID- 17347082 TI - [Intraaortic balloon catheter use as an occluder in ruptured abdominal aortic aneurysm]. PMID- 17347083 TI - [A case of cholesterol emboli syndrome treated with iloprost]. PMID- 17347084 TI - Isolated left ventricular pulsus alternans; an echocardiographic finding in a patient with discrete subaortic stenosis and infective endocarditis. PMID- 17347085 TI - Echocardiographic diagnosis of total anomalous pulmonary venous connection of the infracardiac type. PMID- 17347086 TI - Moyamoya disease and aortic coarctation in a patient with common brachiocephalic trunk. PMID- 17347087 TI - Noncompaction of the ventricular myocardium with bicuspid aortic valve. PMID- 17347088 TI - [Aortic valve replacement with autologous pericardial patch in subvalvular aortic abscess due to Brucella endocarditis]. PMID- 17347089 TI - A salient rectus abdominis hematoma due to enoxaparin. PMID- 17347090 TI - [Quality of life and functional status in congestive heart failure]. PMID- 17347091 TI - [Corridor walk tests and heart failure/ Quality of life and functional status in congestive heart failure]. PMID- 17347092 TI - Coronary rupture to the right ventricle during PTCA for myocardial bridge. PMID- 17347093 TI - Bridge over troubled coronary artery/ Muscular bridge causing non-ST-segment elevation myocardial infarction. PMID- 17347094 TI - Coincidental diagnosis of corrected transposition of the great arteries in an asymptomatic 65-year-old patient. PMID- 17347095 TI - An unusual localization of cyst hydatidosis associated with cardiac hydatid disease. PMID- 17347096 TI - Myxoid tissue fragments in femoral embolectomy material: cardiac myxoma versus myxoid thrombus--a diagnostic dilemma. PMID- 17347097 TI - Tunnel-like ventricular septal defect. PMID- 17347098 TI - A rare chordal anomaly of tricuspid valve in a patient with ventricular septal defect. PMID- 17347100 TI - [The anomalous origin of the left coronary artery from the right aortic sinus of Valsalva]. PMID- 17347099 TI - Unusual combination of coronary artery, bilateral common carotid artery and left common iliac artery aneurysms. PMID- 17347101 TI - Rare coronary artery anomaly: a single coronary artery arising from the right sinus of Valsalva. PMID- 17347102 TI - Left ventricular thrombus in a patient with esophageal carcinoma. PMID- 17347103 TI - Freshwater shrimp-sponge association from an ancient lake. AB - Shrimp-sponge associations occur frequently in marine ecosystems, serving as model systems for the evolution of eusociality. Here, we describe the first known instance of such association in freshwater from an ancient lake in Indonesia. The shrimp Caridina spongicola forms an exclusive and probably commensal association with a yet undescribed spongillinid sponge. Phylogenetic and ecological data suggest a comparatively recent origin of both taxa. Climatic fluctuations may have facilitated speciation and occasional hybridization of the shrimp species, which is derived from a rock-dwelling ancestor. Their extremely localized occurrence in an increasingly disturbed area makes both taxa a conservation priority. PMID- 17347104 TI - Energetic reserves, leptin and testosterone: a refinement of the immunocompetence handicap hypothesis. AB - The immunocompetence handicap hypothesis (ICHH) assumes that testosterone (T), required for the expression of sexual traits, can also incur a cost due to its immunosuppressive properties. However, T-dependent immunosuppression could also arise as an indirect consequence of energy reallocation from the immune system to other metabolic demands. Leptin is mostly produced in lipogenic tissues and its circulating level is positively correlated with the amount of lipid reserves. Leptin also has an important role as immunoenhancer and we suggest that this hormone could play a role as a mediator of the immunosuppressive effect of testosterone. In particular, we propose that only the individuals able to maintain large lipid reserves (with high leptin levels), while sustaining high testosterone levels, might be able to develop sexual displays without an impairment of their immune defences. Here, we tested one of the assumptions underlying this extension of the ICHH: leptin administration should attenuate testosterone-induced immunosuppression. T-implanted and control male zebra finches (Taeniopygia guttata) received daily injections of leptin or phosphate buffered saline. T-implants initially depressed the phytohaemagglutinin-induced immune response. However, T-birds injected with leptin enhanced their immune response to the level of control birds. These results open a new perspective on the study of the ICHH. PMID- 17347105 TI - Systematic placement of an enigmatic Southeast Asian taxon Eupetes macrocerus and implications for the biogeography of a main songbird radiation, the Passerida. AB - Biogeographic connections between Australia and other continents are still poorly understood although the plate tectonics of the Indo-Pacific region is now well described. Eupetes macrocerus is an enigmatic taxon distributed in a small area on the Malay Peninsula and on Sumatra and Borneo. It has generally been associated with Ptilorrhoa in New Guinea on the other side of Wallace's Line, but a relationship with the West African Picathartes has also been suggested. Using three nuclear markers, we demonstrate that Eupetes is the sister taxon of the South African genus Chaetops, and their sister taxon in turn being Picathartes, with a divergence in the Eocene. Thus, this clade is distributed in remote corners of Africa and Asia, which makes the biogeographic history of these birds very intriguing. The most parsimonious explanation would be that they represent a relictual basal group in the Passerida clade established after a long-distance dispersal from the Australo-Papuan region to Africa. Many earlier taxonomic arrangements may have been based on assumptions about relationships with similar looking forms in the same, or adjacent, biogeographic regions, and revisions with molecular data may uncover such cases of neglect of ancient relictual patterns reflecting past connections between the continents. PMID- 17347107 TI - IAGG's role in graduate education in gerontology. PMID- 17347106 TI - Rice functional genomics research in China. AB - Rice functional genomics is a scientific approach that seeks to identify and define the function of rice genes, and uncover when and how genes work together to produce phenotypic traits. Rapid progress in rice genome sequencing has facilitated research in rice functional genomics in China. The Ministry of Science and Technology of China has funded two major rice functional genomics research programmes for building up the infrastructures of the functional genomics study such as developing rice functional genomics tools and resources. The programmes were also aimed at cloning and functional analyses of a number of genes controlling important agronomic traits from rice. National and international collaborations on rice functional genomics study are accelerating rice gene discovery and application. PMID- 17347108 TI - Progress and challenges in graduate education in gerontology: the U.S. Experience. AB - The history and current status of graduate programs in gerontology in the United States are reviewed. Masters degree programs began in 1967, and currently exist at 57 universities in the United States. Challenges for these programs include maintaining enrollment and identifying employment for program graduates, given competition from graduates from other disciplines that have advantages such as state licensure. Doctoral programs in aging began in 1989, with nine current programs. Results to date suggest that graduates with doctorates in gerontology can succeed in academic, policy, research, and business settings. Challenges for these programs include competition from traditional disciplinary doctoral programs. The U.S. experience suggests that successful development of graduate programs in gerontology must be attentive to providing stable academic structures for these programs, and careful consideration of how gerontology graduates will compete with graduates from traditional disciplines and professions. PMID- 17347109 TI - Speculations on the future of taught masters courses in gerontology: lessons from a comparison of England, Scotland, Finland, and Spain. AB - Postgraduate education in gerontology is now widespread within European universities, but, even so, such developments remain very uneven. This paper outlines the variety of provision by describing Master's programmes in a sample of countries: England, Scotland, Finland, and Spain. These programmes illustrate some of the common problems: lack of funding for students, limited availability of academic staff, and reliance on a small core of dedicated teachers. They exhibit many strengths, including the breadth of curricula, high academic standards, high calibre and varied backgrounds of the students, the value of the qualification in employment, and meeting the demands of an ageing Europe. At the same time, these courses are faced with important issues about their sustainability. This paper argues that the demand for generalist courses such as gerontology taught Master's may fall in the coming years due to a combination of factors, such as employers' unwillingness to allow day release and demands by older people themselves for treatment and care by specialists. Generalist courses, this paper argues, may only survive in the biggest and best universities serving large populations and in cities able to attract overseas students. PMID- 17347110 TI - Addressing a nation's challenge: graduate programs in gerontology in Israel. AB - Like other developed nations, Israel has rapidly aged. This demographic revolution has created new challenges for Israeli society. We describe the societal background, including the emerging societal needs, solutions, and problems, as well as the professional principles, which guided us in developing the first two Israeli academic programs in gerontology in Beer-Sheva and Haifa. We further discuss the structures of both programs and their accomplishments. Although both programs were guided by identical needs and principles, geared toward the same multidisciplinary target population, and are dynamic and responsive to the emerging needs and difficulties, they differ in structure. While Haifa's program is flexible, Beer-Sheva's program is structured and divided into three distinct programs, of which only one-the research track-is designed and tailored to the students' interest. The two programs have contributed to increasing interest and research in aging in Israel, enhancing professional cooperation within the universities and with the international scientific community, opening the labor market for the programs' graduates, creating fruitful collaborations with community services, and accelerating the improvement of elderly quality of care. PMID- 17347111 TI - Gerontology-specific graduate programs in Brazil and Colombia. AB - Every year the proportion of elderly people increases at a greater rate compared with other age groups, changing the population structure of most countries. Latin America has been internationally known for its higher percentage of young compared with elderly persons. The United Nations predicts that the proportion of elderly persons in Latin America and the Caribbean will be more similar to world figures in 2020 and even higher in 2040. The increasing elderly population in Latin America has increased the demand for advanced degree professionals with gerontology training. Nevertheless, in spite of training efforts during the last decade, the number of gerontology professionals is still insufficient. In total, the authors were able to locate only ten gerontology programs in Latin America (four in Brazil, two in Argentina, and one each in Uruguay, Peru, Cuba, and Colombia). The programs currently available in Brazil and Colombia are described in an effort to share information on the common characteristics of Master's and PhD degree programs in gerontology in Latin America. The authors concluded that, in Latin America, programs focused exclusively on gerontology are scarce. PMID- 17347112 TI - European initiatives in postgraduate education in gerontology. AB - This paper describes three innovative European initiatives in postgraduate education in gerontology. The first is the European Masters Program in Gerontology (EuMaG), developed as an interdisciplinary joint program, supported and delivered by 22 European universities. Second, the Nordplus initiative to increase mobility of students and staff in the field of gerontology in the European Nordic countries is elaborated. Third, two postgraduate Gerontology and Geriatrics programs offered by the European Centre of Gerontology and Geriatrics, University of Malta are presented. In 1995, the Centre was designated a WHO Collaborating Centre for healthy aging. To provide a context for these initiatives, a short overview is presented of developments in the European Higher Education Area, and the current state and recent developments in gerontology training in Europe is elaborated. The article concludes with discussion of the feasibility and sustainability of European internationalization efforts in education and training in gerontology. PMID- 17347113 TI - Postgraduate education in gerontology in the Asia-Oceania region. AB - This paper provides an overview of opportunities for graduate education in Gerontology in the Asia-Oceania Region. It locates emerging demand in a demographic context, highlighting high rates of growth in the aged population within the Region and growing awareness of governments of the need for appropriate planning. An important component of infrastructure development will be professional access to specialised education about ageing. Of postgraduate programs currently available, most are offered by Australian universities. The trend among providers is towards flexible delivery by distance education using a variety of models, including traditional print-based independent study, cross national partnerships using block or blended teaching models, and predominantly online education. An innovative model developed by a leading local provider, The University of Sydney, is described. StudyAgeOnline is a Web-supported postgraduate coursework program in ageing and aged care for practising health professionals in which short courses can be undertaken as stand-alone modules or build towards a Masters degree. We describe a typical module and discuss how learning and teaching strategies have been designed for practical relevance in a multi-professional and multi-cultural "virtual classroom." PMID- 17347114 TI - Met needs and unmet needs, and satisfaction among Social HMO members. AB - This article reports on a survey of 800 members of four Social HMO demonstration sites, who were receiving home-based, community-based, and short-term institutional services under the demonstration's expanded community care benefits. The survey asked whether members needed help in 11 areas, whether they received help in each area from an informal caregiver, whether they wanted more help from the Social HMO, and whether help provided by both was adequate. Satisfaction with the program and with service coordination was also assessed. The adequacy of informal care differed by problem area, as did the help desired from the Social HMO and its responsiveness. Members were less satisfied when they had weaker informal care, were African American, and when they received inadequate help from the plan with ADLs, transportation, medical access, and managing money. Members were more satisfied when they were professionals, home owners, knew their service coordinator's name (or how to contact her), and received help with their problems. The findings point to the importance of clarifying divisions of labor with informal caregivers, as well as possible expansions in responsibilities for service coordinators and benefits beyond traditional boundaries. PMID- 17347115 TI - PURE: a proposal for more retirement income security. AB - Despite large public policy efforts over the past 30 years, a large minority of households remains consistently inadequately prepared for retirement. If policymakers want to address this shortcoming, public policy has to change from its current path. This paper suggests a system of mandatory private pensions funded by a minimum mandatory contribution of 3% of payroll. In addition, a number of institutional changes are suggested to reduce the costs and risks of individual accounts. PMID- 17347116 TI - Options to liberalize Social Security disabled widow(er)s benefits. AB - Each month, 200,000 widows and 6,000 widowers receive Social Security disabled widow(er)s benefits, each benefit averaging about $550. Among the most economically at-risk Social Security beneficiaries, their benefits are permanently reduced. This paper reviews the legislative history of the disabled widow(er)s benefit, identifying key decisions that gave shape to this benefit. Social Security program data and six years of Current Population Survey data (March Annual Demographic Files, 1995-2000) are used to profile the economic status of current and potential disabled widows. The analysis, including comparison with other widows, provides strong evidence of economic need among disabled widows with, for example, 44% of disabled widow beneficiaries, ages 50 59, having below-poverty incomes compared with 15% of like-aged non-disabled widows. We conclude that serious consideration should be given to extending eligibility to all widow(er)s disabled before the normal retirement age; to providing a benefit equal to 100% of the deceased spouse's private insurance amount (PIA); to eliminating the unnecessarily restrictive seven-year rule; and to protecting beneficiaries from losing their eligibility to Medicaid. Even in the context of today's heated Social Security debate, we suggest that a rare opportunity may exist to garner bipartisan support for meaningful, low-cost improvements, in a benefit that primarily targets women. PMID- 17347117 TI - The Centers for Medicare and Medicaid Services' Nursing Home Case-Mix and Quality Demonstration: a descriptive overview. AB - This paper presents the first comprehensive account of a major national demonstration designed to integrate skilled nursing facilities (SNF) prospective case-mix payment and quality of care. It describes the Centers for Medicare and Medicaid Services' Nursing Home Case-Mix and Quality (NHCMQ) Demonstration-the template for Medicare's SNF Prospective Payment System (PPS) implemented July 1998. The NHCMQ Demonstration provided the basis for one of the most significant changes in SNF reimbursement and quality monitoring policies to date. Prospective reimbursement policies created positive incentive for providers to admit Medicare residents under more equitable payment rates. However, controversy regarding unanticipated perverse provider incentives remains. The quality management system designed under the NHCMQDemonstration is currently used in over 17,000 nursing homes. Furthermore, under the NHCMQ Demonstration, one standardized assessment tool-the MDS-was used to assess a resident's clinical condition, to monitor quality, and to calculate provider reimbursement. Experiences from the NHCMQ Demonstration and continued evaluation of the current national PPS, along with state systems, provide a rich information source regarding prospective, case-mix reimbursement, and provider incentives. PMID- 17347118 TI - Geography still dictates Rx coverage for many near-poor seniors and disabled persons. AB - State-to-state differences in generosity of assistance programs targeted toward poor seniors and people with disabilities have always been the "price of federalism." Typically, these differences are vitiated when federal law enters a field. Not so with the Medicare Prescription Drug, Improvement, and Modernization Act of 2003. States' choices of how much of the uncovered burden of prescription drug costs is left to near-poor elderly and disabled residents continues to vary widely even though Medicare began to provide pharmaceutical coverage beginning January 2006. The purpose of this article is to address the role that state policies play in promoting continued variation in access to prescription drugs. PMID- 17347119 TI - Older people as resources in South Africa: Mpumalanga households. AB - The extended family used to be relied upon to provide subsistence and care for older people in sub-Saharan Africa. However, recently South Africa has seen a reversal of roles, where older people now provide subsistence and care to younger generations; this role reversal is being accelerated by HIV/AIDS deaths among young adults. In most rural households, the non-contributory old age pension (OAP) that is means-tested is an important factor in making older people breadwinners. Using data from the 2004 Mpumalanga Older People's Survey, we examined the changing role of older people, which has been influenced mainly by changes in household structure and old age pension. Findings show that in 63% of matrifocal, multigenerational households, 76% of older people are the sole providers of household necessities, caring for the sick and grandchildren in increasingly skip-generation households. PMID- 17347120 TI - Medical students' knowledge about alcohol and drug problems: results of the medical council of Canada examination. AB - PURPOSE: To determine knowledge of a national sample of medical students about substance withdrawal, screening and early intervention, medical and psychiatric complications of addiction, and treatment options. METHODS: Based on learning objectives developed by medical faculty, twenty-two questions on addictions were included in the 1998 Canadian licensing examination. RESULTS: The exam was written by 858 medical students. The average score on the addiction questions was 64%. Students showed strong knowledge of the clinical features of medical complications. Specific knowledge gaps were identified for withdrawal treatment protocols, low-risk drinking guidelines, taking an alcohol history, substance induced psychiatric disorders, and Alcoholics Anonymous. CONCLUSION: Medical students are knowledge-deficient around key learning objectives in addictions. The deficiencies were in areas of basic knowledge that could be learnt with little difficulty. PMID- 17347121 TI - Preliminary feasibility and efficacy of a brief motivational intervention with psychophysiological feedback for cocaine abuse. AB - Motivational interviewing (MI) with personalized feedback, particularly related to biological markers of risk or harm, has been found effective for alcohol use disorders, but has not been fully investigated in cocaine use disorders. A randomized, controlled pilot study evaluating the feasibility and preliminary efficacy of a brief MI intervention using EEG/ERP graphical feedback for cocaine abusers was conducted. Treatment-seeking cocaine abusers (N = 31) were randomly assigned to a two-session MI intervention or a minimal control condition. All participants received EEG assessments at intake and post-treatment. Results indicated that the MI intervention was feasible and the subjective impact of the EEG feedback was positive. Significant group differences in percentage of cocaine positive urine screens across the study were found, favoring the MI group; 84.9% for the control group and 62.6% in the MI group, p < .05. Further research must determine the specific conditions under which MI is most appropriate and efficacious. PMID- 17347122 TI - Inhalant use and risky behavior correlates in a sample of rural middle school students. AB - This study found 20.4% of children attending a middle school located in rural Mississippi had used inhalants to "get high", a figure that is much larger than the national average. Many (3.4%) students reported they had used inhalants on 10 or more occasions. Inhalant use was most associated with being younger, ever smoking, riding with a driver who had been drinking, and being involved in a fight. Nearly twice as many younger students reported usage in our sample compared to other studies. Longitudinal studies need to be conducted to investigate whether use of inhalants is a precursor to other risky behaviors, and subsequent progression to alcohol abuse or illicit drug use. PMID- 17347123 TI - Inhalant use in Florida youth. AB - PURPOSE: To determine (1) the prevalence of use, (2) risk and protective factors for use of inhalants in Florida youth. METHODS: The Florida Youth Substance Abuse Survey 2004 is a comprehensive assessment of youth substance abuse attitudes and practices obtained by sampling youth from sixty-five counties. RESULTS: The sample consisted of 60,345 students from 6th to 12th grade; ages 10 to 19 + years (mean 14.5 years +/- 4), 53% were female with 59% White, 19% African-American, 16% Hispanic, 5% Native American, 2% Asian and 7% other. Lifetime use was highest among 14 year olds (16.5%), and current use among 13 year olds (16.7%). Females had significantly (p < .000) higher rates than males for lifetime (14.2% vs. 12.7%) and current use (5.1% vs. 4.1%). Native Americans had the highest rates of lifetime use (17%) followed by Whites (15%), mixed/other (15%), Hispanics (14%), Asians (13%), and Blacks (9%). The younger the age of first use of alcohol, cigarettes and marijuana, the higher the lifetime and current prevalence of use of inhalants. Inhalant users were more likely to be depressed, acknowledge deviant behavior and skipping school, have lower grades, have siblings and friends who used illegal substances and parents with a history of antisocial behavior (p < .000). CONCLUSION: Inhalant use may be a marker for adolescents with a high-risk profile for subsequent illegal drug use. Prevention efforts should be directed to these students at an early age. PMID- 17347124 TI - Alcohol and risks for HIV/AIDS among sexually transmitted infection clinic patients in Cape Town, South Africa. AB - Alcohol use is prevalent in South Africa and alcohol use may be associated with higher risk for HIV transmission. This paper reports a study of the association between alcohol use and HIV risk-related behavior among 134 men and 92 women receiving sexually transmitted infection (STI) clinic services in Cape Town, South Africa. Participants completed anonymous surveys of demographic information, substance use, and sexual risk behaviors. Results showed that problem drinking was common among STI clinic patients; 58% of men and 28% of women scored above a cut-off of 9 on the Alcohol Use Disorders Identification Test (AUDIT) suggesting possible problem drinking and 46% of men and 19% of women scored above 12 on the AUDIT indicating probable drinking problems. For men, heavier alcohol use was associated with having multiple sex partners in the past month, less condom use, and having a history of sexually assaulting women. Among women, higher scores on the AUDIT were also related to having multiple sex partners as well as a history of exchanging sex for money or materials. The association between alcohol use and sexual risk behaviors in a population at high risk for HIV transmission demonstrates the need for integrating alcohol risk reduction counseling with HIV prevention counseling among STI clinic patients in South Africa. PMID- 17347125 TI - Illy: clinical and public health implications of a street drug. AB - We conducted a prospective, observational study of patients presenting to an emergency department with suspected use of a street drug known as "illy" to identify the active ingredient in "illy" and describe the clinical presentation and outcomes associated with its use. Vital signs, mental status, restraint use, and urine toxicology (UT) results were recorded. Patients were interviewed about drug use patterns and co-ingestants. Fifty-nine patients (89.9% males) with a mean age of 22 years (SD +/- 4.37) were enrolled over a 34-month period. UT was obtained in 61% of patients; of these 91.7% tested positive for phencyclidine (PCP). Seventy-eight percent of patients were discharged, (15.3%) required psychiatric evaluation; 3 were admitted, one died in the ED. Patients reported concurrent drug use (54%) and at-risk drinking (50%). PCP is likely the active component of "illy". Most patients require observation and supportive care only, however major complications including death may occur. PMID- 17347126 TI - HIV incidence, retention, and changes of high-risk behaviors among rural injection drug users in Guangxi, China. AB - BACKGROUND: A prospective observational study of HIV seroincidence among high risk injection drug users (IDU) was carried out in Guangxi, China. The primary objectives of this study were (1) to estimate HIV seroincidence (2) to estimate participant retention rate and (3) to evaluate changes in drug use and sexual behavior over a one year period. METHODS: Five hundred HIV seronegative IDU were enrolled. HIV-1 incidence and retention rates were analyzed as a function of sociodemographic, behavioral, and recruitment variables. Changes in drug use and sexual behavior were analyzed at the baseline, 6-month and 12-month follow- up visits. RESULTS: At 12 months of follow-up, the HIV-1 incidence rate was 3.1 per 100 person years, [95% CI: (1.6%; 5.2%)] and participant retention rate was 87%. Reported changes in high-risk behaviors over 12-months included significant decreases in the frequency of heroin injection, in direct or indirect sharing of injection equipment, and in the number of sexual partners. CONCLUSIONS: HIV incidence is high among IDU in Guangxi, China despite a self-reported decrease in some high risk behaviors over the course of the study. PMID- 17347127 TI - Mothball withdrawal encephalopathy: case report and review of paradichlorobenzene neurotoxicity. AB - Paradichlorobenzene (PDB) is a common household deodorant and pesticide found in room deodorizers, toilet bowl fresheners, and some mothballs. Although human exposure to the compound is generally limited and harmless, PDB in larger doses can produce neurotoxic effects, including a chemical "high" similar to that seen with inhalants such as toluene. Although rare, frank addiction to PDB has been reported, and, in such cases, has been associated with gait ataxia, tremor, dysarthria, limb weakness, and bradyphrenia, in various combinations. In such cases, the adverse neurologic consequences have been presumed to result from a direct toxic effect of this small, organic molecule. We report a case of chronic mothball ingestion where profound encephalopathy with cognitive, pyramidal, extrapyramidal, and cerebellar features appears to have been largely the result of PDB withdrawal, rather than direct toxicity. This case raises important questions about the mechanism of PDB neurotoxicity and possible treatment options for PDB-addicted patients. We propose that in cases with clear clinical deterioration after abstinence, readministration and gradual taper of PDB might be considered a therapeutic option. PMID- 17347128 TI - Adjuvant radiotherapy for stage I endometrial cancer: systematic review and meta analysis. AB - The role of adjuvant radiotherapy in stage I endometrial cancer following surgery remains unclear. The management for these patients varies widely, particularly in stage I patients with different risk factors. Using the methodology of Cochrane Collaboration, we did a systematic and meta-analysis of all know randomised controlled trials which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer. The meta-analysis was carried out on four trials (three published and one unpublished) and a total of 1770 patients. The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 [95% confidence interval (CI) 0.17-0.44, P < 0.00001], which is a 72% reduction in the risk of pelvic relapse (95% CI 56% to 83%) and an absolute risk reduction of 6% (95% CI of 4% to 8%). The reduction in the risk of locoregional recurrence did not translate into a reduction in the risks of death from all causes, endometrial cancer death or distant recurrence. A subgroup analysis showed a trend towards the reduction in the risks of death from all causes and endometrial cancer in patients with multiple high risk factors (including stage 1c and grade 3). External beam pelvic radiotherapy should be considered in patients with multiple high-risk features including stage 1c and grade 3. However, it carries an inherent risk of damage and toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors. PMID- 17347129 TI - Autoantibodies in breast cancer: their use as an aid to early diagnosis. AB - BACKGROUND: There is increasing evidence that the immune system produces a humoral response to cancer-derived antigens. This study assessed the diagnostic potential of autoantibodies to multiple known tumour-associated proteins. PATIENTS AND METHODS: Sera from normal controls (n = 94), primary breast cancer patients (n = 97) and patients with ductal carcinoma in situ (DCIS) (n = 40) were investigated for the presence of autoantibodies to p53, c-myc, HER2, NY-ESO-1, BRCA1, BRCA2 and MUC1 antigens by enzyme-linked immunosorbent assay. RESULTS: Reproducibly elevated levels of autoantibodies were seen in at least one of the six antigens in 64% of primary breast cancer patient sera and 45% of patients with DCIS at a specificity of 85%. No significant differences were seen when patients were subdivided by age, tumour size, histological grade, lymph node status or detection methodology. CONCLUSIONS: Autoantibodies against one or more of these tumour-associated antigens appears to indicate the presence of early stage breast cancers. Autoantibody assays against a panel of antigens could be used as an aid to mammography in the detection and diagnosis of early primary breast cancer, especially in younger women at increased risk of breast cancer where mammography is known to have reduced sensitivity and specificity. PMID- 17347130 TI - The mutagenic potential of non-homologous end joining in the absence of the NHEJ core factors Ku70/80, DNA-PKcs and XRCC4-LigIV. AB - Non-homologous end joining (NHEJ), the major pathway of double-strand break (DSB) repair in mammalian cells, comprises two subpathways: one that requires the three core factors Ku70/80, DNA-PKcs and XRCC4/LigIV (DNA-PK-dependent NHEJ) and the other that is independent of these factors. Using a cell-free NHEJ assay, we have investigated the ability of three Chinese hamster ovary (CHO) mutants deficient in Ku80 (xrs6), DNA-PKcs (XR-C1) and XRCC4 (XR-1) in comparison with CHO-K1 wild type cells to rejoin non-compatible DSB ends. Both NHEJ efficiency and fidelity are strongly reduced in the mutants with xrs6 and XR-1 exhibiting the strongest reduction and XR-C1 displaying a phenotype intermediate between the wild-type and the other two mutants indicating a non-essential but facilitating role of DNA PKcs in NHEJ. The decrease in fidelity in the mutants is expressed by an increase of deletion junctions formed at microhomologies (microhom) near the DSB (microhomology-mediated non-homologous end joining: microhomNHEJ). Using a novel microhomNHEJ assay, we show that microhom regions of 6-10 bp that are located directly at the DSB termini strongly enhance the mutagenic microhomNHEJ reaction even in the wild type. Due to its error proneness, DNA-PK-independent microhomNHEJ may actively promote genome instability. It will, therefore, be of increasing importance to examine NHEJ fidelity in the context with tumorigenesis and cellular senescence for which we here provide two efficient and reliable tools. PMID- 17347131 TI - A truncated MYB transcription factor from Antirrhinum majus regulates epidermal cell outgrowth. AB - Plant MYB genes can be divided into subgroups on the basis of additional conserved regions of sequence. In some cases, genes within a subgroup share similarities in function, as well as sequence. The functions of three proteins in subgroup 9 have been described, with AmMYBMX regulating the differentiation of conical-papillate petal epidermal cells, PhMYB1 involved in extending the growth of these cells, and AmMYBML1 involved in differentiation of several petal epidermal cell types. Here, the isolation of a gene encoding a new member of MYB subgroup 9, AmMYBML3 (Antirrhinum majus MYB MIXTA-LIKE 3) is described, which contains the defining regions of conserved sequence but is lacking the majority of the C-terminus, including the amphipathic alpha-helix presumed necessary for transcriptional activation. AmMYBML3 is expressed in all aerial organs, but its expression is restricted to outgrowing epidermal cells, including trichomes, stigmatic papillae, and petal conical-papillate cells. Ectopic expression of AmMYBML3 in tobacco results in the formation of conical-papillate cells in the usually flat carpel epidermis. These data suggest that this protein is capable of altering epidermal development, thus resulting in cellular outgrowth, despite the missing C-terminus, and may act in conjunction with other transcriptional activators to enhance cellular outgrowth from the epidermis of all aerial organs. PMID- 17347132 TI - QTLs for shelf life in lettuce co-locate with those for leaf biophysical properties but not with those for leaf developmental traits. AB - Developmental and biophysical leaf characteristics that influence post-harvest shelf life in lettuce, an important leafy crop, have been examined. The traits were studied using 60 informative F9 recombinant inbed lines (RILs) derived from a cross between cultivated lettuce (Lactuca sativa cv. Salinas) and wild lettuce (L. serriola acc. UC96US23). Quantitative trait loci (QTLs) for shelf life co located most closely with those for leaf biophysical properties such as plasticity, elasticity, and breakstrength, suggesting that these are appropriate targets for molecular breeding for improved shelf life. Significant correlations were found between shelf life and leaf size, leaf weight, leaf chlorophyll content, leaf stomatal index, and epidermal cell number per leaf, indicating that these pre-harvest leaf development traits confer post-harvest properties. By studying the population in two contrasting environments in northern and southern Europe, the genotype by environment interaction effects of the QTLs relevant to leaf development and shelf life were assessed. In total, 107 QTLs, distributed on all nine linkage groups, were detected from the 29 traits. Only five QTLs were common in both environments. Several areas where many QTLs co-located (hotspots) on the genome were identified, with relatively little overlap between developmental hotspots and those relating to shelf life. However, QTLs for leaf biophysical properties (breakstrength, plasticity, and elasticity) and cell area correlated well with shelf life, confirming that the ideal ideotype lettuce should have small cells with strong cell walls. The identification of QTLs for leaf development, strength, and longevity will lead to a better understanding of processability at a genetic and cellular level, and allow the improvement of salad leaf quality through marker-assisted breeding. PMID- 17347133 TI - Relationships of root conductivity and aquaporin gene expression in Pisum sativum: diurnal patterns and the response to HgCl2 and ABA. AB - Experiments were undertaken to test how aquaporins (AQPs) facilitate the uptake of water by roots of Pisum sativum. Changes in PsPIP2-1 gene expression and root hydraulic conductivity (Lpr) were measured in response to the time of day as well as treatment of the roots with a compound that reduced Lpr [i.e. mercuric chloride (HgCl2)] and one that was intended to increase Lpr [abscisic acid (ABA)]. There was a diurnal rhythm in PsPIP2-1 expression in lateral roots that was strongly correlated with diurnal changes in Lpr. Taproots also displayed a rhythm in PsPIP2-1 expression, but this was offset from that of Lpr. This suggested that changes in Lpr were mediated by changes in PsPIP2-1 mRNA transcript abundance. Reduction of Lpr by HgCl2 treatment was accompanied by an increase in PsPIP2-1 expression, implying that PsPIP2-1 expression may have increased to compensate for AQPs blocked by mercury. ABA usually increased Lpr, but changes in PsPIP2-1 were variable and the direction of the response was strongly dependent on the dose of ABA that was applied. Overall, the coincident rhythms in Lpr and PIP2 expression and response to AQP blockage are consistent with the hypothesis that Lpr changes are mediated, at least in part, by changes in PsPIP2-1 expression. Inconsistencies with ABA data may have been due to more complex interactions of ABA with AQP channels. PMID- 17347134 TI - Manganese inhalation by rhesus monkeys is associated with brain regional changes in biomarkers of neurotoxicity. AB - The purpose of this study was to evaluate biochemical markers of neurotoxicity following subchronic manganese sulfate (MnSO(4)) inhalation. Juvenile rhesus monkeys were exposed to MnSO(4) at 0, 0.06, 0.3, or 1.5 mg Mn/m(3) for 65 days. Glutamine synthetase (GS), glutamate transporters (glutamate transporter-1 [GLT 1] and glutamate/aspartate transporter [GLAST]) and tyrosine hydroxylase (TH) protein levels, metallothionein (MT), GLT-1, GLAST, TH and GS mRNA levels, and total glutathione (GSH) levels were assessed in known targets (caudate, globus pallidus, putamen) as well as the cerebellum, frontal cortex, and olfactory cortex. All MnSO(4)-exposed monkeys had decreased pallidal GS protein, decreased caudate GLT-1 mRNA, decreased pallidal GLAST protein, and increased olfactory cortical TH mRNA levels. Monkeys exposed to MnSO(4) at 0.06 or 0.3 mg Mn/m(3) had significantly increased pallidal mRNA levels for GLT-1, GLAST, and TH. Monkeys exposed to MnSO(4) at > or = 0.3 mg Mn/m(3) had several alterations including decreased frontal cortical MT mRNA, decreased caudate, globus pallidus, olfactory cortex, and cerebellum GLT-1 protein, decreased olfactory cortex and cerebellum GLAST protein, increased cerebellar GLAST mRNA, and decreased pallidal TH protein levels. Lastly, GSH levels were significantly increased in the frontal cortex and decreased in the caudate of monkeys exposed to the 1.5-mg Mn/m(3) compared to the controls. Overall, as in our previous studies, we observed that increased Mn concentrations due to airborne Mn exposure differentially affects biomarkers in each brain region (e.g., GSH was increased in the frontal cortex and decreased in the caudate despite two- to threefold increases in Mn concentrations in these regions). PMID- 17347135 TI - Evaluation of the contact and respiratory sensitization potential of volatile organic compounds generated by simulated indoor air chemistry. AB - Up to 60 million people working indoors experience symptoms such as eye, nose and throat irritation, headache, and fatigue. Investigations into these complaints have ascribed the effects to volatile organic compounds (VOCs) emitted from building materials, cleaning formulations, or other consumer products. New compounds can result when the VOCs react with hydroxyl or nitrate radicals or ozone present in indoor environments. Several oxygenated organic compounds, such as glyoxal, methylglyoxal, glycolaldehyde, and diacetyl, have been identified as possible reaction products of indoor environment chemistry. Although research has previously identified diacetyl and glyoxal as sensitizers, additional experiments were conducted in these studies to further classify their sensitization potential. Sensitization potential of these four compounds was assessed using quantitative structure-activity relationship (QSAR) programs. Derek for Windows and National Institute for Occupational Safety and Health logistic regression predicted all compounds to be sensitizers, while TOPKAT 6.2 predicted all compounds except for methylglyoxal. All compounds were tested in a combined irritancy and local lymph node assay (LLNA). All compounds except for glyoxal were found to be irritants and all tested positive in the LLNA with EC3 values ranging from 0.42 to 1.9%. Methylglyoxal significantly increased both the B220(+) and IgE(+)B220(+) cell populations in the draining lymph nodes and total serum IgE levels. The four compounds generated by indoor air chemistry were predicted by QSAR and animal modeling to be sensitizers, with the potential for methylglyoxal to induce IgE. The identification of these compounds as sensitizers may help to explain some of the health effects associated with indoor air complaints. PMID- 17347136 TI - Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo. AB - Radiation therapy is a primary treatment modality for brain tumors, yet it has been linked to the increased incidence of secondary, post-radiation therapy cancers. These cancers are thought to be linked to indirect radiation-induced bystander effect. Bystander effect occurs when irradiated cells communicate damage to nearby, non-irradiated 'bystander' cells, ultimately contributing to genome destabilization in the non-exposed cells. Recent evidence suggests that bystander effect may be epigenetic in nature; however, characterization of epigenetic mechanisms involved in bystander effect generation and its long-term persistence has yet to be defined. To investigate the possibility that localized X-ray irradiation induces persistent bystander effects in distant tissue, we monitored the induction of epigenetic changes (i.e. alterations in DNA methylation, histone methylation and microRNA (miRNA) expression) in the rat spleen tissue 24 h and 7 months after localized cranial exposure to 20 Gy of X rays. We found that localized cranial radiation exposure led to the induction of bystander effect in lead-shielded, distant spleen tissue. Specifically, this exposure caused the profound epigenetic dysregulation in the bystander spleen tissue that manifested as a significant loss of global DNA methylation, alterations in methylation of long interspersed nucleotide element-1 (LINE-1) retrotransposable elements and down-regulation of DNA methyltransferases and methyl-binding protein methyl CpG binding protein 2 (MeCP2). Further, irradiation significantly altered expression of miR-194, a miRNA putatively targeting both DNA methyltransferase-3a and MeCP2. This study is the first to report conclusive evidence of the long-term persistence of bystander effects in radiation carcinogenesis target organ (spleen) upon localized distant exposure using the doses comparable with those used for clinical brain tumor treatments. PMID- 17347137 TI - The role of PTEN in prostate cancer cell tropism to the bone micro-environment. AB - Little is known about the role of the tumor suppressor gene phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in prostate cancer bone metastasis. To explore this, we used a pTetOn PTEN cell line in which PTEN expression was reconstituted in a PTEN-null bone metastatic human prostate cancer cell line, LnCaP-C4-2. We found that C4-2 cells selectively migrated toward conditioned medium from primary mouse calvaria cells compared with that derived from lung fibroblasts. Further evaluation with conditioned medium from an established mouse calvaria osteoblast cell line and control non-osteoblast cell line indicates that osteoblastic characteristics convey this specific migration to C4-2 cells. We evaluated promiscuously metastatic PC-3 prostate as well as T24T and UMUC-3 bladder cells and found they did not have a specific migratory response to calvaria-conditioned medium as did C4-2. Induction of PTEN expression inhibited the motility of C4-2 cells toward calvaria-conditioned medium but had no effect on migration toward lung-conditioned medium and this inhibitory effect was dependent on the PTEN lipid phosphatase activity. Calvaria- but not lung conditioned medium induced activation of the small GTPase Rac1. Constitutively active Rac1 but not focal adhesion kinase or Cdc42 could rescue cells from the inhibitory effect of PTEN on cell migration and PTEN induction was observed to inhibit Rac1 activation in response to calvaria-conditioned medium. Our results support the notion that loss of PTEN function in human prostate cancer may specifically facilitate bone rather than other organ metastasis and suggest that Rac1, as a PTEN effector, may contribute to this metastatic tropism. PMID- 17347138 TI - Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. AB - Consumers of higher levels of Brassica vegetables, particularly those of the genus Brassica (broccoli, Brussels sprouts and cabbage), reduce their susceptibility to cancer at a variety of organ sites. Brassica vegetables contain high concentrations of glucosinolates that can be hydrolyzed by the plant enzyme, myrosinase, or intestinal microflora to isothiocyanates, potent inducers of cytoprotective enzymes and inhibitors of carcinogenesis. Oral administration of either the isothiocyanate, sulforaphane, or its glucosinolate precursor, glucoraphanin, inhibits mammary carcinogenesis in rats treated with 7,12 dimethylbenz[a]anthracene. In this study, we sought to determine whether sulforaphane exerts a direct chemopreventive action on animal and human mammary tissue. The pharmacokinetics and pharmacodynamics of a single 150 mumol oral dose of sulforaphane were evaluated in the rat mammary gland. We detected sulforaphane metabolites at concentrations known to alter gene expression in cell culture. Elevated cytoprotective NAD(P)H:quinone oxidoreductase (NQO1) and heme oxygenase 1 (HO-1) gene transcripts were measured using quantitative real-time polymerase chain reaction. An observed 3-fold increase in NQO1 enzymatic activity, as well as 4-fold elevated immunostaining of HO-1 in rat mammary epithelium, provides strong evidence of a pronounced pharmacodynamic action of sulforaphane. In a subsequent pilot study, eight healthy women undergoing reduction mammoplasty were given a single dose of a broccoli sprout preparation containing 200 mumol of sulforaphane. Following oral dosing, sulforaphane metabolites were readily measurable in human breast tissue enriched for epithelial cells. These findings provide a strong rationale for evaluating the protective effects of a broccoli sprout preparation in clinical trials of women at risk for breast cancer. PMID- 17347139 TI - Control of virus infection by tumour suppressors. AB - An increasing number of tumour suppressor genes are induced by interferons (IFNs) and may play an important role in the control of cell proliferation induced by this cytokine. In addition, pathways triggered by both tumour suppressors and IFN converge as common targets for non-related tumour viruses. The inhibition of the IFN response by animal viruses is explained by the fundamental role that IFN plays to control virus infection. However, the reasons why many viruses, including those that do not require the replication of the host, target tumour suppressor pathways are varied and are still under investigation. Here we review those findings that support that tumour suppressors may have a role in the control of virus infection. PMID- 17347140 TI - The suppression of aberrant crypt multiplicity in colonic tissue of 1,2 dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes. AB - Colorectal cancer is the second leading cause of cancer deaths worldwide with diet playing a prominent role in disease initiation and progression. Flavonoids are secondary plant compounds that are suggested as protective ingredients of a diet rich in fruits and vegetables. We here tested whether flavone, a flavonoid that proved to be an effective apoptosis inducer in colon cancer cells in culture, can affect the development of aberrant crypt foci (ACFs) in C57BL/6J mice in vivo when preneoplastic lesions were induced by the carcinogen 1,2 dimethylhydrazine (DMH). Flavone applied at either a low dose (15 mg/kg body wt per day) or a high dose (400 mg/kg body wt per day) reduced the numbers of ACFs significantly, independent of whether it was supplied simultaneously with the carcinogen (blocking group) or subsequent to the tumor induction phase (suppressing group). Proteome analysis performed in colonic tissue samples revealed that flavone treatment increased the expression of a number of Krebs cycle enzymes in the suppressing group and this was associated with reduced crypt multiplicity. It suggests that mitochondrial substrate oxidation is increased by flavone in colonic cells in vivo as already observed in HT-29 cells in vitro as the prime mechanism underlying tumor cell apoptosis induction by flavone. In conclusion, flavone reduces the number of ACFs in DMH-treated mice at doses that can be achieved for flavonoids by a diet rich in fruits and vegetables. Moreover, reduction in crypt multiplicity by flavone is most probably due to the preservation of a normal oxidative metabolism. PMID- 17347141 TI - Lipid peroxidation dominates the chemistry of DNA adduct formation in a mouse model of inflammation. AB - In an effort to define the prevalent DNA damage chemistry-associated chronic inflammation, we have quantified 12 DNA damage products in tissues from the SJL mouse model of nitric oxide (NO) overproduction. Using liquid chromatography-mass spectrometry/MS and immunoblot techniques, we analyzed spleen, liver and kidney from RcsX-stimulated and control mice for the level of the following adducts: the DNA oxidation products 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), guanidinohydantoin (Gh), oxazolone (Ox); 5-guanidino-4-nitroimidazole (NitroIm); spiroiminodihydantoin (Sp) and M(1)dG; the nitrosative deamination products 2' deoxyxanthosine, 2'-deoxyoxanosine (dO), 2'-deoxyinosine and 2'-deoxyuridine and the lipid peroxidation-derived adducts 1,N(6)-etheno-deoxyadenosine and 1,N(2) etheno-deoxyguanosine. The levels of dO, Gh, Ox, NitroIm and Sp were all below a detection limit of approximately 1 lesion per 10(7) bases. Whereas there were only modest increases in the spleens of RcsX-treated compared with control mice for the nucleobase deamination products (10-30%) and the DNA oxidation products 8 oxodG (10%) and M(1)dG (50%), there were large (3- to 4-fold) increases in the levels of 1,N(6)-etheno-deoxyadenosine and 1,N(2)-etheno-deoxyguanosine. Similar results were obtained with the liver and with an organ not considered to be a target for inflammation in the SJL mouse, the kidney. This latter observation suggests that oxidative and nitrosative stresses associated with inflammation can affect tissues at a distance from the activated macrophages responsible for NO overproduction during chronic inflammation. These results reveal the complexity of NO chemistry in vivo and support an important role for lipids in the pathophysiology of inflammation. PMID- 17347142 TI - Context-dependent GATA factor function: combinatorial requirements for transcriptional control in hematopoietic and endothelial cells. AB - GATA factors are fundamental components of developmentally important transcriptional networks. By contrast to common mechanisms in which transacting factors function directly at promoters, the hematopoietic GATA factors GATA-1 and GATA-2 often assemble dispersed complexes over broad chromosomal regions. For example, GATA-1 and GATA-2 occupy five conserved regions over approximately 100 kb of the Gata2 locus in the transcriptionally repressed and active states, respectively, in erythroid cells. Since it is unknown whether the individual complexes exert qualitatively distinct or identical functions to regulate Gata2 transcription in vivo, we compared the activity of the -3.9 and +9.5 kb sites of the Gata2 locus in transgenic mice. The +9.5 site functioned as an autonomous enhancer in the endothelium and fetal liver of embryonic day 11 embryos, whereas the -3.9 site lacked such activity. Mechanistic studies demonstrated critical requirements for a GATA motif and a neighboring E-box within the +9.5 site for enhancer activity in endothelial and hematopoietic cells. Surprisingly, whereas this GATA-E-box composite motif was sufficient for enhancer activity in an erythroid precursor cell line, its enhancer function in primary human endothelial cells required additional regulatory modules. These results identify the first molecular determinant of Gata2 transcription in vascular endothelium, composed of a core enhancer module active in both endothelial and hematopoietic cells and regulatory modules preferentially required in endothelial cells. PMID- 17347143 TI - Analysis of CD95 threshold signaling: triggering of CD95 (FAS/APO-1) at low concentrations primarily results in survival signaling. AB - Recently we generated a mathematical model (Bentele, M., Lavrik, I., Ulrich, M., Stosser, S., Heermann, D. W., Kalthoff, H., Krammer, P. H., and Eils, R. (2004) J. Cell Biol. 166, 839-851) of signaling in CD95(Fas/APO-1)-mediated apoptosis. Mathematical modeling in combination with experimental data provided new insights into CD95-mediated apoptosis and allowed us to establish a threshold mechanism of life and death. Here, we further assessed the predictability of the model experimentally by a detailed analysis of the threshold behavior of CD95 signaling. Using the model predictions for the mechanism of the threshold behavior we found that the CD95 DISC (death-inducing signaling complex) is formed at the cell membrane upon stimulation with low concentrations of agonistic anti APO-1 monoclonal antibodies; however, activation of procaspase-8 at the DISC is blocked due to high cellular FLICE-inhibitory protein recruitment into the DISC. Given that death signaling does not occur upon CD95 stimulation at low (threshold) anti-APO-1 concentrations, we also analyzed survival signaling, focusing on mitogen-activated protein kinase activation. Interestingly, we found that mitogen-activated protein kinase activation takes place under threshold conditions. These findings show that triggering of CD95 can signal both life or death, depending on the strength of the stimulus. PMID- 17347144 TI - Structure and conformational changes in the C-terminal domain of the beta2 adrenoceptor: insights from fluorescence resonance energy transfer studies. AB - The C terminus of the beta(2)-adrenoceptor (AR) interacts with G protein-coupled receptor kinases and arrestins in an agonist-dependent manner, suggesting that conformational changes induced by ligands in the transmembrane domains are transmitted to the C terminus. We used fluorescence resonance energy transfer (FRET) to examine ligand-induced structural changes in the distance between two positions on the beta(2)-AR C terminus and cysteine 265 (Cys-265) at the cytoplasmic end of transmembrane domain 6. The donor fluorophore FlAsH (Fluorescein Arsenical Helix binder) was attached to a CCPGCC motif introduced at position 351-356 in the proximal C terminus or at the distal C terminus. An acceptor fluorophore, Alexa Fluor 568, was attached to Cys-265. FRET analyses revealed that the average distances between Cys-265 and the proximal and distal FlAsH sites were 57 and 62A(,) respectively. These relatively large distances suggest that the C terminus is in an extended, relatively unstructured conformation. Nevertheless, we observed ligand-specific changes in FRET. All ligands induced an increase in FRET between the proximal C-terminal FlAsH site and Cys-265. Ligands that have been shown to induce arrestin-dependent ERK activation, including the catecholamine agonists and the inverse agonist ICI118551, led to a decrease in FRET between the distal FlAsH site and Cys-265, whereas other ligands had no effect or induced a small increase in FRET. Taken together the results provide new insight into the structure of the C terminus of the beta(2)-AR as well as ligand-induced conformational changes that may be relevant to arrestin-dependent regulation and signaling. PMID- 17347145 TI - Cadherin conformations associated with dimerization and adhesion. AB - To investigate conformations of C-cadherin associated with functional activity and physiological regulation, we generated monoclonal antibodies (mAbs) that bind differentially to monomeric or dimeric forms. These mAbs recognize conformational epitopes at multiple sites along the C-cadherin ectodomain aside from the well known Trp-2-mediated dimer interface in the N-terminal EC1 domain. Group 1 mAbs, which bind monomer better than dimer and the Trp-2-mutated protein (W2A) better than wild type, recognize epitopes in EC4 or EC5. Dimerization of the W2A mutant protein via a C-terminal immunoglobulin Fc domain restored the dimeric mAb binding properties to EC4-5 and partial homophilic binding activity but did not restore full cell adhesion activity. Group 2 and Group 3 mAbs, which bind dimer better than monomer and wild type better than W2A, recognize epitopes in EC1 and the interface between EC1 and EC2, respectively. None of the mAbs could distinguish between different physiological states of C-cadherin at the cell surface of either Xenopus embryonic cells or Colo 205 cultured cells, demonstrating that changes in dimerization do not underlie regulation of adhesion activity. On the cell surface the EC3-EC5 domains are much less accessible to mAb binding than EC1-EC2, suggesting that they are masked by the state of cadherin organization or by other molecules. Thus, the EC2-EC5 domains either reflect, or are involved in, cadherin dimerization and organization at the cell surface. PMID- 17347146 TI - Segments crucial for membrane translocation and pore-forming activity of Bordetella adenylate cyclase toxin. AB - Bordetella adenylate cyclase toxin-hemolysin (CyaA, AC-Hly, or ACT) permeabilizes cell membranes by forming small cation-selective (hemolytic) pores and subverts cellular signaling by delivering into host cells an adenylate cyclase (AC) enzyme that converts ATP to cAMP. Both AC delivery and pore formation were previously shown to involve a predicted amphipathic alpha-helix(502-522) containing a pair of negatively charged Glu(509) and Glu(516) residues. Another predicted transmembrane alpha-helix(565-591) comprises a Glu(570) and Glu(581) pair. We examined the roles of these glutamates in the activity of CyaA. Substitutions of Glu(516) increased specific hemolytic activity of CyaA by two different molecular mechanisms. Replacement of Glu(516) by positively charged lysine residue (E516K) increased the propensity of CyaA to form pores, whereas proline (E516P) or glutamine (E516Q) substitutions extended the lifetime of open single pore units. All three substitutions also caused a drop of pore selectivity for cations. Substitutions of Glu(570) and Glu(581) by helix-breaking proline or positively charged lysine residue reduced (E570K, E581P) or ablated (E570P, E581K) AC membrane translocation. Moreover, E570P, E570K, and E581P substitutions down modulated also the specific hemolytic activity of CyaA. In contrast, the E581K substitution enhanced the hemolytic activity of CyaA 4 times, increasing both the frequency of formation and lifetime of toxin pores. Negative charge at position 570, but not at position 581, was found to be essential for cation selectivity of the pore, suggesting a role of Glu(570) in ion filtering inside or close to pore mouth. The pairs of glutamate residues in the predicted transmembrane segments of CyaA thus appear to play a key functional role in membrane translocation and pore forming activities of CyaA. PMID- 17347147 TI - Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. AB - Recombinant bispecific antibodies such as tandem scFv molecules (taFv), diabodies (Db), or single chain diabodies (scDb) have shown to be able to retarget T lymphocytes to tumor cells, leading to their destruction. However, therapeutic efficacy is hampered by a short serum half-life of these small molecules having molecule masses of 50-60 kDa. Thus, improvement of the pharmacokinetic properties of small bispecific antibody formats is required to enhance efficacy in vivo. In this study, we generated several recombinant bispecific antibody-albumin fusion proteins and analyzed these molecules for biological activity and pharmacokinetic properties. Three recombinant antibody formats were produced by fusing two different scFv molecules, bispecific scDb or taFv molecules, respectively, to human serum albumin (HSA). These constructs (scFv(2)-HSA, scDb-HSA, taFv-HSA), directed against the tumor antigen carcinoembryonic antigen (CEA) and the T cell receptor complex molecule CD3, retained full binding capacity to both antigens compared with unfused scFv, scDb, and taFv molecules. Tumor antigen-specific retargeting and activation of T cells as monitored by interleukin-2 release was observed for scDb, scDb-HSA, taFv-HSA, and to a lesser extent for scFv(2)-HSA. T cell activation could be further enhanced by a target cell-specific costimulatory signal provided by a B7-DbCEA fusion protein. Furthermore, we could demonstrate that fusion to serum albumin strongly increases circulation time of recombinant bispecific antibodies. In addition, our comparative study indicates that single chain diabody-albumin fusion proteins seem to be the most promising format for further studying cytotoxic activities in vitro and in vivo. PMID- 17347148 TI - Distinct targeting and fusion functions of the PX and SNARE domains of yeast vacuolar Vam7p. AB - Regulated membrane fusion requires organelle tethering, enrichment of selected proteins and lipids at the fusion site, bilayer distortion, and lipid rearrangement. Yeast vacuole homotypic fusion requires regulatory lipids (ergosterol, diacylglycerol, and phosphoinositides), the Rab family GTPase Ypt7p, the multisubunit Ypt7p-effector complex HOPS (homotypic fusion and vacuole protein sorting), and four SNAREs. One SNARE, Vam7p, has an N-terminal PX domain which binds to phosphatidylinositol 3-phosphate (PI(3)P) and to HOPS and a C terminal SNARE domain but no apolar membrane anchor. We have exploited an in vitro reaction of vacuole fusion to analyze the functions of each domain, removing the PX domain or mutating it to abolish its PI(3)P affinity. Lowering the PI(3)P affinity of the PX domain, or even deleting the PX domain, affects the fusion K(m) for Vam7p but not the maximal fusion rate. Fusion driven by the SNARE domain alone is strikingly enhanced by the PLC inhibitor U73122 through enhanced binding of Vam7p SNARE domain to vacuoles, and the further addition of Plc1p blocks this U73122 effect. The PX domain, through its affinities for phosphoinositides and HOPS, is thus exclusively required for enhancing the targeting of Vam7p rather than for execution of the Vam7p functions in HOPS.SNARE complex assembly and fusion. PMID- 17347149 TI - Novel interaction of the 60S ribosomal subunit export adapter Nmd3 at the nuclear pore complex. AB - Nuclear export of the large (60S) ribosomal subunit depends on the adapter protein Nmd3 to provide a nuclear export signal (NES). The leucine-rich NES is recognized by the export receptor Crm1 to mediate export via interaction with the nuclear pore complex (NPC). Here, we show that certain mutant Nmd3 proteins that are impaired for binding to the 60S subunit accumulate at the nuclear envelope. These mutant proteins also show enhanced binding to Crm1, both in vivo and in vitro. Although their interaction with the NPC is dependent on recognition of the NES by Crm1, their interaction with Crm1 is not strictly dependent on RanGTP. Using a collection of GFP-tagged nucleoporin mutants, we identified several nucleoporins, including components of the Nup82 complex that copurified with the mutant Nmd3. The Nup82 complex is on the cytoplasmic face of the NPC and has previously been shown to be important as a terminal binding site for Crm1 mediated export. Mutations in the Nup82 complex led to accumulation of wild-type Nmd3 in the nucleoplasm, suggesting that the interaction of mutant Nmd3 with the Nup82 complex reflects a defect in the bona fide export pathway for the 60S subunit. These results suggest that in the absence of the ribosome, Nmd3 is not efficiently released from Crm1 at the NPC. PMID- 17347150 TI - Interaction between heat shock transcription factors (HSFs) and divergent binding sequences: binding specificities of yeast HSFs and human HSF1. AB - The target genes of the heat shock transcription factor (HSF) contain a cis acting sequence, the heat shock element (HSE), which consists of multiple inverted repeats of the sequence 5'-nGAAn-3'. Using data acquired in this and a previous study, we have identified the HSEs in 59 of 62 target genes of Saccharomyces cerevisiae Hsf1. The Hsf1 protein recognizes continuous and discontinuous repeats of the nGAAn unit; the nucleotide sequences and configuration of the units diverge slightly among functional HSEs. When Schizosaccharomyces pombe HSF was expressed in S. cerevisiae cells, heat shock induced S. pombe HSF to bind to various HSE types, which properly activated transcription from almost all target genes, suggesting that the S. pombe genome also contains divergent HSEs. Human HSF1 induced the heat shock response via HSEs with continuous units in S. cerevisiae cells but failed to do so via HSEs with discontinuous units. Binding of human HSF1 to the discontinuous type of HSE was observed in vitro but was significantly inhibited in vivo. These results show that human HSF1 recognizes HSEs in a slightly different way than yeast HSFs and suggest that the configuration of the unit is an important determinant for HSF HSE interactions. PMID- 17347151 TI - Cyclosporin A and FK506 inhibit IL-12p40 production through the calmodulin/calmodulin-dependent protein kinase-activated phosphoinositide 3 kinase in lipopolysaccharide-stimulated human monocytic cells. AB - Cyclosporine-A (CyA) and FK506 are potent immunosuppressive agents because of their ability to suppress the production of Th1 cytokines including interleukin (IL)-12. However, the mechanisms underlying the inhibitory effects of CyA and FK506 on the production of IL-12p40, a critical component of IL-12, remain unknown. Both CyA and FK506 are potent inhibitors of calcineurin in the calcium signaling pathway. Interestingly, calcium and phosphoinositide 3-kinase (PI3K) signaling pathways have been shown to negatively regulate lipopolysaccharide (LPS)-induced murine IL-12p40 production. Contrary to these observations, we show that LPS-induced IL-12p40 production in human monocytic cells is positively regulated by the calcium pathway and in particular by calmodulin-(CaM) and CaM dependent protein kinase-II (CaMK-II)-activated PI3K. Furthermore, LPS-induced IL 12p40 production was regulated by the p110alpha catalytic subunit of PI3K. Moreover, LPS induced IL-12p40 production through the CaM/CaMK-II-activated NFkappaB and AP-1 transcription factors. LPS-induced IL-12p40 production is known to be regulated by the c-Jun N-terminal kinase (JNK) pathway. Importantly, both CyA and FK506 down-regulated LPS-induced IL-12p40 transcription by inhibiting CaM/CaMK-II-activated PI3K and their downstream transcription factors NFkappaB and AP-1 independent of the JNK pathway. PMID- 17347152 TI - Heparanase enhances syndecan-1 shedding: a novel mechanism for stimulation of tumor growth and metastasis. AB - When shed from the cell surface, the heparan sulfate proteoglycan syndecan-1 can facilitate the growth, angiogenesis, and metastasis of tumors. Here we report that tumor cell expression of heparanase, an enzyme known to be a potent promoter of tumor progression and metastasis, regulates both the level and location of syndecan-1 within the tumor microenvironment by enhancing its synthesis and subsequent shedding from the tumor cell surface. Heparanase regulation of syndecan-1 is detected in both human myeloma and breast cancer cell lines. This regulation requires the presence of active enzyme, because mutated forms of heparanase lacking heparan sulfate-degrading activity failed to influence syndecan-1 expression or shedding. Removal of heparan sulfate from the cell surface using bacterial heparitinase dramatically accelerated syndecan-1 shedding, suggesting that the effects of heparanase on syndecan-1 expression by tumor cells may be due, at least in part, to enzymatic removal or reduction in the size of heparan sulfate chains. Animals bearing tumors formed from cells expressing high levels of heparanase or animals transgenic for heparanase expression exhibited elevated levels of serum syndecan-1 as compared with controls, indicating that heparanase regulation of syndecan-1 expression and shedding can occur in vivo and impact cancer progression and perhaps other pathological states. These results reveal a new mechanism by which heparanase promotes an aggressive tumor phenotype and suggests that heparanase and syndecan 1 act synergistically to fine tune the tumor microenvironment and ensure robust tumor growth. PMID- 17347154 TI - Helix-helix interactions between homo- and heterodimeric gamma-carboxyglutamate containing conantokin peptides and their derivatives. AB - The conantokins are a family of small, naturally occurring gamma-carboxyglutamate (Gla)-rich peptides that specifically antagonize the N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptor. One member of this family, conantokin-G (con-G), undergoes Ca(2+)-mediated self-assembly to form an antiparallel helical dimer. Subunit interactions in this complex are incumbent upon intermolecular Ca(2+) bridging of Gla residues spaced at i, i + 4, i + 7, i + 11 intervals within the monomer. Herein, we further probe the molecular determinants governing such helix-helix interactions. Select variants were synthesized to evaluate the contributions of non-Gla residues to conantokin self-association. Con-G dimerization was shown to be exothermic and accompanied by positive heat capacity changes. Using positional Gla variants of conantokin-R (con-R), a non-dimerizing conantokin, i, i + 4, i + 7, i + 11 Gla spacing alone was shown to be insufficient for self-assembly. The Ca(2+)-dependent antiparallel heterodimerization of con-G and con-T(K7 gamma), two peptides that harbor optimal Gla spacing, was established. Last, the effects of covalently constrained con-G dipeptides on NMDA-evoked current in HEK293 cells expressing combinations of NR1a, NR1b, NR2A, and NR2B subunits of the NMDA receptor were investigated. The antiparallel dipeptide was unique in its ability to potentiate current at NR1a/2A receptors and, like monomeric con-G, was inhibitory at NR1a/2B and NR1b/2B combinations. In contrast, the parallel species was completely inactive at all subunit combinations tested. These results suggest that, under physiological Ca(2+) concentrations, equilibrium levels of con-G dimer most likely exist in an antiparallel orientation and exert effects on NMDA receptor activity that differ from the monomer. PMID- 17347153 TI - Two functionally divergent UDP-Gal nucleotide sugar transporters participate in phosphoglycan synthesis in Leishmania major. AB - In the protozoan parasite Leishmania, abundant surface and secreted molecules, such as lipophosphoglycan (LPG) and proteophosphoglycans (PPGs), contain extensive galactose in the form of phosphoglycans (PGs) based on (Gal-Man-PO(4)) repeating units. PGs are synthesized in the parasite Golgi apparatus and require transport of cytoplasmic nucleotide sugar precursors to the Golgi lumen by nucleotide sugar transporters (NSTs). GDP-Man transport is mediated by the LPG2 gene product, and here we focused on transporters for UDP-Gal. Data base mining revealed 12 candidate NST genes in the L. major genome, including LPG2 as well as a candidate endoplasmic reticulum UDP-glucose transporter (HUT1L) and several pseudogenes. Gene knock-out studies established that two genes (LPG5A and LPG5B) encoded UDP-Gal NSTs. Although the single lpg5A(-) and lpg5B(-) mutants produced PGs, an lpg5A(-)/5B(-) double mutant was completely deficient. PG synthesis was restored in the lpg5A(-)/5B(-) mutant by heterologous expression of the human UDP Gal transporter, and heterologous expression of LPG5A and LPG5B rescued the glycosylation defects of the mammalian Lec8 mutant, which is deficient in UDP-Gal uptake. Interestingly, the LPG5A and LPG5B functions overlap but are not equivalent, since the lpg5A(-) mutant showed a partial defect in LPG but not PPG phosphoglycosylation, whereas the lpg5B(-) mutant showed a partial defect in PPG but not LPG phosphoglycosylation. Identification of these key NSTs in Leishmania will facilitate the dissection of glycoconjugate synthesis and its role(s) in the parasite life cycle and further our understanding of NSTs generally. PMID- 17347156 TI - Zebrafish ribonucleases are bactericidal: implications for the origin of the vertebrate RNase A superfamily. AB - Understanding the evolutionary origin of the ribonuclease (RNase) A superfamily is of great interest because the superfamily is the sole vertebrate-specific enzyme family known to date. Although mammalian RNases have a diverse array of biochemical and physiological functions, the original function of the superfamily at its birth is enigmatic. Such information may be obtained by studying basal lineages of the vertebrate phylogeny and is necessary for discerning how and why this superfamily originated. Here, we clone and characterize 3 RNase genes from the zebrafish, the most basal vertebrate examined for RNases. We report 1) that all the 3 zebrafish RNases are ribonucleolytically active, with one of them having an RNase activity comparable to that of bovine RNase A, the prototype of the superfamily; 2) that 2 zebrafish RNases have prominent expressions in adult liver and gut, whereas the 3rd is expressed in adult eye and heart; and 3) that all 3 RNases have antibacterial activities in vitro. These results, together with the presence of antibacterial and/or antiviral activities in multiple distantly related mammalian RNases, strongly suggest that the superfamily started as a host defense mechanism in vertebrate evolution. PMID- 17347157 TI - A reversible jump method for Bayesian phylogenetic inference with a nonhomogeneous substitution model. AB - Nonhomogeneous substitution models have been introduced for phylogenetic inference when the substitution process is nonstationary, for example, when sequence composition differs between lineages. Existing models can have many parameters, and it is then difficult and computationally expensive to learn the parameters and to select the optimal model complexity. We extend an existing nonhomogeneous substitution model by introducing a reversible jump Markov chain Monte Carlo method for efficient Bayesian inference of the model order along with other phylogenetic parameters of interest. We also introduce a new hierarchical prior which leads to more reasonable results when only a small number of lineages share a particular substitution process. The method is implemented in the PHASE software, which includes specialized substitution models for RNA genes with conserved secondary structure. We apply an RNA-specific nonhomogeneous model to a structure-based alignment of rRNA sequences spanning the entire tree of life. A previous study of the same genes from a similar set of species found robust evidence for a mesophilic last universal common ancestor (LUCA) by inference of the G+C composition at the root of the tree. In the present study, we find that the helical GC composition at the root is strongly dependent on the root position. With a bacterial rooting, we find that there is no longer strong support for either a mesophile or a thermophile LUCA, although a hyperthermophile LUCA remains unlikely. We discuss reasons why results using only RNA helices may differ from results using all aligned sites when applying nonhomogeneous models to RNA genes. PMID- 17347158 TI - Assessing the determinants of evolutionary rates in the presence of noise. AB - Although protein sequences are known to evolve at vastly different rates, little is known about what determines their rate of evolution. However, a recent study using principal component regression (PCR) has concluded that evolutionary rates in yeast are primarily governed by a single determinant related to translation frequency. Here, we demonstrate that noise in biological data can confound PCRs, leading to spurious conclusions. When equalizing noise levels across 7 predictor variables used in previous studies, we find no evidence that protein evolution is dominated by a single determinant. Our results indicate that a variety of factors -including expression level, gene dispensability, and protein-protein interactions--may independently affect evolutionary rates in yeast. More accurate measurements or more sophisticated statistical techniques will be required to determine which one, if any, of these factors dominates protein evolution. PMID- 17347159 TI - In vitro and in vivo approaches to study angiogenesis in the pathophysiology and therapy of endometriosis. AB - Endometriosis represents one of the most common gynaecological disorders. According to the implantation theory, angiogenesis is a major prerequisite for the initiation and progression of the disease. Thus, during the last decade, many studies have focused on the mechanisms regulating angiogenesis in endometriotic lesions. For this purpose, sophisticated in vitro and in vivo approaches have been established, which are highlighted in this review. Enzyme-linked immunosorbent assays demonstrate the imbalance of pro- and anti-angiogenic growth factors in isolated peritoneal fluid from endometriosis patients. Histological, immunohistochemical and gene expression analyses of endometriotic tissue provide detailed information on the angio-architecture of endometriotic lesions and the different growth factor expression by various cell populations. Moreover, cell culture systems are useful tools for the identification of hormonal and immunological factors involved in the angiogenic process. Finally, sophisticated in vivo models, such as rodent models of peritoneal endometriosis as well as the chorioallantoic membrane assay and the dorsal skinfold chamber, allow for the detailed analysis of blood vessel development in ectopic endometrium and the efficacy of angiogenesis inhibitors. The findings resulting from all these approaches will help to provide better insights into the pathophysiology of endometriosis and to establish new anti-angiogenic treatment strategies for the future. PMID- 17347160 TI - Low-dose aspirin for in vitro fertilization: a systematic review and meta analysis. AB - Despite recent advances in ovarian stimulation regimens and laboratory techniques, the pregnancy rate of assisted reproduction remains relatively low. New methods that would potentially improve implantation rates are needed. One proposed strategy involves enhancement of blood flow at the implantation site with the use of low-dose aspirin. We conducted a systematic review and meta analysis to investigate the effect of low-dose aspirin on likelihood of pregnancy in women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). An electronic search of the literature was conducted targeting reports published over the last 26 years. Only randomized controlled trials (RCTs) comparing aspirin with placebo or no treatment in IVF/ICSI women were included in the meta-analysis. A number of relevant outcomes including pregnancy and live birth (LB) rates were investigated. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated using a random-effects model. Inter-study heterogeneity among the trials was assessed using the Cochran's Q test. Ten RCTs were identified from the literature search, six of which met the criteria for inclusion in the meta-analysis. Clinical pregnancy (CP) rate per embryo transfer (ET) was not found to be significantly different between patients who received low-dose aspirin and those who received placebo or no treatment (RR 1.09, 95% CI 0.92-1.29). None of the other outcomes, including CP per cycle, spontaneous abortion or ectopic pregnancy per CP and LB rate per cycle or ET was found to differ significantly between the compared groups. On the basis of up-to-date evidence, low-dose aspirin has no substantial positive effect on likelihood of pregnancy and, therefore, it should not be routinely recommended for women undergoing IVF/ICSI. PMID- 17347161 TI - Does the prostrate-leaved geophyte Brunsvigia orientalis utilize soil-derived CO2 for photosynthesis? AB - BACKGROUND AND AIMS: A test was made of the hypothesis that the prostrate growth habit of the leaves of the geophyte Brunsvigia orientalis enables utilization of soil-derived CO(2) and is related to the presence of lysigenous air-filled channels characteristic of B. orientalis leaves. METHODS: Brunsvigia orientalis was sampled at a field site. Leaf anatomy, stomatal density, leaf/soil gas exchange characteristics and soil atmosphere and leaf delta(13)C isotope abundances were examined. KEY RESULTS: The leaves of B. orientalis have large lysigenous air-filled channels separating the upper and lower surfaces of the leaves. The upper surface comprised approx. 70 % of the leaf mass and 75 % of the leaf N (mmol g(-1)). Between 20 % and 30 % of the stomatal conductance and CO(2) assimilation was through the lower surface of the leaf. CO(2) efflux rates from the soil surface were up to 5.4 micromol m(-2) s(-1) while photosynthetic fluxes through the lower surface of the leaves were approx. 7 micromol m(-2) s(-1). However, the utilization of soil-derived CO(2) only altered the leaf delta(13)C isotope abundance of the prostrate leaves by a small amount. Using delta(13)C values it was estimated that 7 % of the leaf tissue C was derived from soil derived CO(2). CONCLUSIONS: A small proportion of photosynthetically fixed CO(2) was derived from the soil, with minimal associated transpirational H(2)O loss into the space between the leaf and soil. The soil-derived CO(2), taken up through the lower surface was probably assimilated by the palisade tissue in the upper surface of the leaf which was exposed to sunlight and where most of the leaf N was located. The occurrence of lysigenous air channels in the leaves may provide longitudinal strength without impaired transfer of CO(2) taken up through the lower surface to the upper surface. PMID- 17347162 TI - Ethylene production is associated with germination but not seed dormancy in red rice. AB - BACKGROUND AND AIMS: The relationship between ethylene production and both seed dormancy and germination was investigated using red rice (weedy rice) as a model species. METHODS: Both fully dormant and after-ripened (non-dormant) naked caryopses were incubated with or without inhibitors of ethylene synthesis [aminoethoxyvinylglycine (AVG)] and perception [silver thiosulfate (STS)], or in the presence of the natural ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). The kinetics of ethylene emissions were measured with a sensitive laser-photoacoustic system. KEY RESULTS: Dormant red rice caryopses did not produce ethylene. In non-dormant caryopses, ethylene evolution never preceded the first visible stage of germination (pericarp splitting), and ethylene inhibitors completely blocked ethylene production, but not pericarp splitting. Accordingly, endogenous ACC appeared to be lacking before pericarp splitting. However, early seedling growth (radicle or coleoptile attaining the length of 1 mm) followed ethylene evolution and was delayed by the inhibitors. Wounding the dormant caryopses induced them to germinate and produce ethylene, but their germination was slow and pericarp splitting could be speeded up by ethylene. CONCLUSIONS: The findings suggest that, in red rice, endogenous ethylene stimulates the growth of the nascent seedling, but does not affect seed dormancy or germination inception. Correspondingly, this phytohormone does not play a role in the dormancy breakage induced by wounding, but accelerates germination after such breakage has occurred. PMID- 17347163 TI - Day length affects the dynamics of leaf expansion and cellular development in Arabidopsis thaliana partially through floral transition timing. AB - BACKGROUND AND AIMS: Plant aerial development is well known to be affected by day length in terms of the timing and developmental stage of floral transition. Arabidopsis thaliana is a 'long day' plant in which the time to flower is delayed by short days and leaf number is increased. The aim of the work presented here was to determine the effects of different day lengths on individual leaf area expansion. The effect of flower emergence per se on the regulation of leaf expansion was also tested in this study. METHODS: Care was taken to ensure that day length was the only source of micro-meteorological variation. The dynamics of individual leaf expansion were analysed in Ler and Col-0 plants grown under five day lengths in five independent experiments. Responses at cellular level were analysed in Ler plants grown under various day lengths and treatments to alter the onset of flowering. KEY RESULTS: When the same leaf position was compared, the final leaf area and both the relative and absolute rates of leaf expansion were decreased by short days, whereas the duration of leaf expansion was increased. Epidermal cell number and cell area were also altered by day-length treatments and some of these responses could be mimicked by manipulating the date of flowering. CONCLUSIONS: Both the dynamics and cellular bases of leaf development are altered by differences in day length even when visible phenotypes are absent. To some extent, cell area and its response to day length are controlled by whole plant control mechanisms associated with the onset of flowering. PMID- 17347164 TI - Lymphangiogenesis of normal endometrium and endometrial adenocarcinoma. AB - BACKGROUND: Information about lymphatics and lymphangiogenesis in the human endometrium is limited. We investigated the distribution of endometrial lymphatic vessels during the normal menstrual cycle and in association with endometrial adenocarcinoma and investigated the expression of lymphangiogenic growth factors, vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor-3 (VEGF R3). METHODS AND RESULTS: Full thickness uterine samples (n = 23 proliferative; n = 23 secretory) and endometrial adenocarcinoma samples (n = 7 grade I; n = 10 grade III) were collected for the study and analysed by immunohistochemistry and western blotting. Lymphatic vessels of the functionalis were significantly reduced compared with basalis (P = 0.001) across the menstrual cycle with lymphatics of the basalis sometimes intimately associated with spiral arterioles. Lymphatic vessels of endometrial adenocarcinomas were located intra-tumoural and peri-tumoural with significant increases in the peri-tumoural lymphatic vessels compared with normal basalis (P = 0.02). Interestingly, high-grade adenocarcinoma vessels containing tumour emboli demonstrated a mixed blood/lymphatic endothelial cell phenotype. VEGF-C and VEGF-D were immunolocalized in glandular epithelium and some stromal cells with the staining intensity of this localization increasing in endometrial adenocarcinoma. Protein analysis identified VEGF-C (58, 41, 31 and 21 kD) and VEGF-D (56, 41, 31 and 21 kD) and VEGF-R3 (148 and 65 kD) peptides in normal endometrium, with significant increases in several of these peptides for VEGF-C and VEGF-D and no changes in protein expression for VEGF-R3 in endometrial adenocarcinoma. CONCLUSION: Endometrial lymphatics are significantly reduced in the functionalis, and increases in endometrial adenocarcinoma peri-tumoural lymphatics are associated with increases in VEGF-C and VEGF-D peptides. PMID- 17347165 TI - Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development. AB - BACKGROUND The optimal time for GnRH antagonist initiation is still debatable. The purpose of the current randomized controlled trial is to provide endocrine and follicular data during ovarian stimulation for IVF in patients with polycystic ovarian syndrome (PCOS) treated either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol. METHODS Randomized patients in both groups (antagonist: n = 26; long agonist: n = 52) received oral contraceptive pill treatment for three weeks and a starting dose of 150 IU of follitropin beta. The primary outcome was E(2) level on Day 5 of stimulation, while secondary outcomes were follicular development, LH during ovarian stimulation and progesterone levels. RESULTS Significantly more follicles on days 5, 7 and 8 of stimulation, significantly higher estradiol (E(2)) levels on days 1, 3, 5, 7 and 8 and significantly higher progesterone levels on days 1, 5 and 8 of stimulation were observed in the antagonist when compared with the agonist group. E(2) was approximately twice as high in the antagonist when compared with the agonist group on day 5 of stimulation (432 versus 204 pg ml(-1), P lt; 0.001). These differences were accompanied by significantly lower LH levels on days 3 and 5 and significantly higher LH levels on days 1, 7 and 8 of stimulation in the antagonist when compared with the agonist group. CONCLUSIONS In PCOS patients undergoing IVF, initiation of GnRH antagonist concomitantly with recombinant FSH is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol. PMID- 17347166 TI - Estrogen affects post-menopausal women differently than estrogen plus progestin replacement therapy. AB - BACKGROUND: In the Women's Health Initiative Randomized Controlled Trial (WHI RCT), estrogen-only treatment compared with combined estrogen-progestin treatment resulted in less coronary artery disease, no increase in breast cancer and no reduction in colorectal cancer. Since we previously reasonably replicated the combined estrogen-progestin WHI RCT using the UK General Practice Research Database (GPRD), estrogen-only treatment was investigated using a similar methodology. METHODS: This GPRD study simulated the estrogen-only WHI RCT of women who had undergone a hysterectomy except for randomization. The primary analysis examined 11 572 unexposed and 6890 Exposed women (aged 55-79) treated with conjugated equine estrogen and was compared with the combined estrogen progestin GPRD study. RESULTS: At baseline, women with a hysterectomy exhibited more cardiovascular disease than those with an intact uterus. In the estrogen only GPRD study, adjusted hazard ratios (HRs) were 0.50 (0.38-0.67) for myocardial infarction (MI), 1.13 (0.91-1.41) for breast cancer, and 1.18 (0.72 1.92) for colorectal cancer. Compared to the HRs in the estrogen-progestin GPRD study, the estrogen-only results are significantly lower for MI and breast cancer and higher for colon cancer, a pattern similar to the WHI RCT study comparisons. CONCLUSIONS: This study confirms that post-menopausal women in the overall population respond differently to estrogen-only treatment compared with estrogen progestin treatment, due to different hormone regimens and/or increased cardiovascular disease in hysterectomized women. PMID- 17347167 TI - High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development. AB - BACKGROUND: Bone morphogenetic protein-15 (BMP-15) has been shown to influence oocyte maturation and quality. However, no relationship has been established between BMP-15 and oocyte quality/embryonic development in humans. The aim of this study is to investigate BMP-15 level in human follicular fluid (FF) and its possible role in determining oocyte quality and developmental potential. METHODS: A total of 79 oocytes and their corresponding FF from 79 women undergoing ICSI were examined. Individual oocytes were inseminated and subsequently assessed on the basis of their fertilization, cleavage and preimplantation development. BMP 15, FSH, estradiol (E(2)) and progesterone levels of FF were also analysed via the techniques of western blot or radioimmunoassay. RESULTS: Higher FF BMP-15 levels were observed in the fertilized and cleaved groups versus the unfertilized and uncleaved groups, respectively (P < 0.05). The best (Grade I) embryo morphology was associated with higher FF BMP-15 levels than Grade II or III embryos (P < 0.01). A significant positive correlation was found between BMP-15 and E(2) levels in the same follicle. CONCLUSION: The present study demonstrates that the BMP-15 level in FF appears to be a potential factor in predicting oocyte quality and subsequent embryo development, and is correlated with E(2) level, which may additionally be a valuable predictor of oocyte fertilization. PMID- 17347168 TI - ESHRE Task Force on Ethics and Law 12: oocyte donation for non-reproductive purposes. AB - The present paper focuses on oocyte donation for non-reproductive purposes, i.e. research and future therapy. The general principles of research ethics apply to these interventions. The proportionality principle demands that any possible harms to the oocyte donors should be proportionate to the possible benefits for society. The non-maleficence principle states that every reasonable effort should be made to minimize risks for donors. The position is adopted that, mutatis mutandis, women who donate oocytes for research should be treated similarly to research participants in clinical trials. This implies, among other things, that oocyte donors for research should receive reimbursement for all costs of the procedure and should get compensation for the time lost and inconvenience suffered during the treatment. In order to avoid malpractice and exploitation of poor women, a number of measures are proposed such as a ban on the import of oocytes. PMID- 17347169 TI - Effect of fibronectin on proteasome activity, acrosome reaction, tyrosine phosphorylation and intracellular calcium concentrations of human sperm. AB - BACKGROUND: Previously we showed that the human sperm proteasome plays significant roles during mammalian fertilization. Here we studied the effect of fibronectin (Fn), an extracellular matrix protein present in the cumulus oophorus of the oocyte, on proteasome activity, acrosome reaction, intracellular calcium concentration ([Ca(2+)](i)) and protein tyrosine phosphorylation of human sperm. METHODS: Aliquots of motile sperm were incubated for 15 min (T0), 5 h (T5) and 18 h (T18), at 37 degrees C, 5% CO(2) and 95% air with Fn (0-100 microg/ml). The chymotrypsin- and trypsin-like activity of the proteasome was measured using the fluorogenic substrates, Suc-Leu-Leu-Val-Tyr-AMC and Boc-Gln-Ala-Arg-AMC, respectively. At T18, sperm aliquots were incubated for 15 min with Fn and/or progesterone in the presence or absence of epoxomicin (a proteasome inhibitor). The percentage of viable acrosome reacted sperm was evaluated using the Fluorescein isothiocyanate (FITC)-labeled Pisum sativum agglutinin. Tyrosine phosphorylation was evaluated by western blot and [Ca(2+)](i) using fura 2. RESULTS: Fn stimulated both enzymatic activities of the proteasome and the acrosome reaction of human sperm. Progesterone enhanced and epoxomicin drastically inhibited the effect of Fn. Fn treatment also increased the [Ca(2+)](i). Western blot analysis revealed that Fn increased tyrosine protein phosphorylation and that some proteasome subunits became tyrosine phosphorylated upon Fn treatment. CONCLUSIONS: These results suggest that Fn activates the proteasome and induces the acrosome reaction in human sperm. This effect may involve binding with specific receptors (integrins) on the sperm surface and the activation of tyrosine kinases. PMID- 17347170 TI - Localization and variable expression of G alpha(i2) in human endometrium and Fallopian tubes. AB - BACKGROUND: Heterotrimeric G proteins take part in membrane-mediated cell signalling and have a role in hormonal regulation. This study clarifies the expression and localization of the G protein subunit G alpha(i2) in the human endometrium and Fallopian tube and changes in G alpha(i2) expression in human endometrium during the menstrual cycle. METHODS: The expression of G alpha(i2) was identified by Polymerase chain reaction (PCR), and localization confirmed by immunostaining. Cyclic changes in G alpha(i2) expression during the menstrual cycle were evaluated by quantitative real-time PCR. RESULTS: We found G alpha(i2) to be expressed in human endometrium, Fallopian tube tissue and in primary cultures of Fallopian tube epithelial cells. Our studies revealed enriched localization of G alpha(i2) in Fallopian tube cilia and in endometrial glands. We showed that G alpha(i2) expression in human endometrium changes significantly during the menstrual cycle, with a higher level in the secretory versus proliferative and menstrual phases (P < 0.05). CONCLUSIONS: G alpha(i2) is specifically localized in human Fallopian tube epithelial cells, particularly in the cilia, and is likely to have a cilia-specific role in reproduction. Significantly variable expression of G alpha(i2) during the menstrual cycle suggests G alpha(i2) might be under hormonal regulation in the female reproductive tract in vivo. PMID- 17347171 TI - Human heart-type fatty-acid-binding protein as a point-of-care test in the early diagnosis of acute myocardial infarction. AB - BACKGROUND: At very early stages of acute myocardial infarction (AMI), highly sensitive biomarkers are still lacking. AIM: To evaluate the utility of human heart-type fatty acid-binding protein (h-FABP) for early diagnosis of AMI. DESIGN: Prospective diagnostic study. METHODS: Consecutive patients presenting to the emergency department with chest pain or dyspnoea within 24 h of symptom onset were included. At presentation, the h-FABP test result was compared to the standard diagnostic work-up, including repeated ECG and troponin T measurements. Sensitivity analysis was performed for inconclusive tests. RESULTS: We enrolled 280 patients presenting to hospital with a median symptom onset of 3 h (IQR 2-6 h): 109 (39%) had AMI. At presentation, h-FABP had a sensitivity of 69% (95%CI 59 77) and specificity of 74% (95%CI 66-80); 45 tests were false-positive and 34 were false-negative. Omitting inconclusive tests increased sensitivity and specificity only slightly. AMI was identified significantly earlier by h-FABP than by troponin T (24 vs. 8 patients, p=0.005). DISCUSSION: Although h-FABP can help to detect myocardial damage at an early stage in patients with chest pain or dyspnoea, it appears unsuitable as a stand-alone test for ruling out AMI. PMID- 17347172 TI - Regions of low endothelial shear stress are the sites where coronary plaque progresses and vascular remodelling occurs in humans: an in vivo serial study. AB - AIM: We performed serial intracoronary studies of patients with stable coronary artery disease (CAD) to investigate the relationships among baseline endothelial shear stress (ESS), CAD progression, and vascular remodelling. Local haemodynamic factors are critical determinants of plaque progression, vascular remodelling, and clinical CAD manifestations. METHODS AND RESULTS: The 3-D anatomy of coronary arteries with lumen obstruction <50% was determined by fusing intracoronary ultrasound and angiographic images in 13 patients at baseline and 8 +/- 2 months later. Cross-sectional area of plaque, lumen, and external elastic membrane (EEM), and coronary flow were measured. Local ESS was calculated. Subsegments with similar ESS were categorized based on low (<12 dynes/cm(2)) and moderate/higher ESS (> or =12 dynes/cm(2)). There were 47 subsegments of similar baseline ESS: nine with low ESS and 38 with moderate/higher ESS. Median subsegment length was 6.9 mm (25th-75th percentiles = 4.2-12.0), and median area of similar ESS of 52.6 mm(2) (25th-75th percentiles = 26.9-88.0). Subsegments with low ESS exhibited plaque progression when compared with subsegments with moderate/higher ESS (33.3% vs. 7.9%, respectively, P = 0.009 adjusted for clustering of lesions within patients) and constrictive remodelling (44.0% vs. 5.3%, respectively, P = 0.16 adjusted for clustering of lesions within patients). Expansive remodelling occurred with similar frequency in subsegments with low vs. moderate/higher baseline ESS. CONCLUSION: Plaque progresses in subsegments with low ESS, associated with either constrictive or expansive remodelling. Different mechanisms are likely responsible for expansive remodelling in different local vascular environments. Early in vivo identification of arterial subsegments likely to develop high-risk plaque characteristics may allow for selective interventions to avoid adverse cardiac outcomes. PMID- 17347173 TI - Matrix metalloproteinase and heart failure: is it time to move from research to clinical laboratories? PMID- 17347174 TI - A look at drug eluting stents with optical coherence tomography. PMID- 17347176 TI - Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both? AB - AIMS: Despite advancements over the past years, normal reperfusion at the myocardial level is not achieved in approximately every other patient with ST elevation myocardial infarction. In the current work, we aimed at reviewing the role of the coronary microcirculation in the development and outcome of this acute coronary syndrome entity. METHODS AND RESULTS: A PubMed/Medline search was performed with the key words acute coronary syndrome, acute myocardial infarction, coronary artery disease, endothelial dysfunction, microcirculation, and reperfusion. The synthesis of the information points to myocardial microcirculatory dysfunction as a consequence of a primary epicardial event, based on the vulnerable plaque concept. As an alternative theory, microcirculatory dysfunction may contribute to the clinical course of the acute coronary event, based on the vulnerable patient concept. The pros and cons of these two viewpoints are to be discussed and their influence on patient management is to be considered. CONCLUSION: Microcirculatory dysfunction in ST elevation myocardial infarction can be cause, consequence or both according to non-traditional and traditional concepts. PMID- 17347175 TI - Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves. AB - AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT. PMID- 17347177 TI - Population pharmacokinetics of a single daily intramuscular dose of gentamicin in children with severe malnutrition. AB - OBJECTIVES: The World Health Organization recommends that all children admitted with severe malnutrition should routinely receive parenteral ampicillin and gentamicin; despite this, mortality remains high. Since this population group is at risk of altered volume of distribution, we aimed to study the population pharmacokinetics of once daily gentamicin (7.5 mg/kg) in children with severe malnutrition and to evaluate clinical factors affecting pharmacokinetic parameters. METHODS: Thirty-four children aged 0.5-10 years were studied. One hundred and thirty-two gentamicin concentrations (median of four per patient), drawn 0.4-24.6 h after administration of the intramuscular dose, were analysed. The data were fitted by a two-compartment model using the population package NONMEM. RESULTS: Gentamicin was rapidly absorbed and all concentrations measured within the first 2 h after administration were > 8 mg/L (indicating that satisfactory peak concentrations were achieved). Ninety-eight percent of samples measured more than 20 h after the dose were < 1 mg/L. The best model included weight, and it was found that high base deficit, high creatinine concentration and low temperature (all markers of hypovolaemic shock) reduced clearance (CL/F). Weight influenced volume of the central (V1/F) and peripheral (V2/F) compartments, and high base deficit reduced V2/F and intercompartmental CL (Q/F). Interindividual variability in CL was 26%, in V1/F 33% and in V2/F and Q/F was 52%. Individual estimates of CL/F ranged from 0.02 to 0.16 (median 0.10) L/h/kg and those of Vss/F from 0.26 to 1.31 (median 0.67) L/kg. Initial half-lives had a median of 1.4 h and elimination half-lives and a median of 14.9 h. Excessive concentrations were observed in one patient who had signs of renal impairment and shock. CONCLUSIONS: Although a daily dose of 7.5 mg/kg achieves satisfactory gentamicin concentrations in the majority of patients, patients with renal impairment and shock may be at risk of accumulation with 24 hourly dosing. Further studies of gentamicin pharmacokinetics in this group are now needed to inform future international guideline recommendations. PMID- 17347178 TI - Extended double disc synergy testing reveals a low prevalence of extended spectrum beta-lactamases in Enterobacter spp. in Vienna, Austria. AB - OBJECTIVES: The aims of this study were to determine the prevalence of extended spectrum beta-lactamases (ESBLs) in AmpC-carrying Enterobacter spp. in a tertiary care university hospital in Vienna, Austria, and to implement a cost-effective strategy to detect ESBLs in this particular genus on a routine basis. METHODS: Clinical Enterobacter isolates (n=208) were investigated by means of (i) an inhibitor-potentiated diffusion test using cefpodoxime, (ii) an expanded double disc diffusion synergy test (discs of cefotaxime, ceftazidime, cefpodoxime and cefepime placed around amoxicillin/clavulanic acid), (iii) the Etest ESBL screening method and (iv) the cefoxitin-cefotaxime antagonist test. Cefepime MICs were determined by separate Etests. RESULTS: Of 208 isolates, 76 (37%), 18 (9%) and 92 (44%) were derepressed, partially derepressed and inducible AmpC producers, respectively. Eight (4%) ESBL-producing Enterobacter strains could be detected, all of which would have been detected using disc-based tests. Six out of eight strains were genetically not related, as assessed by random amplification of polymorphic DNA. Typing results were confirmed by means of enterobacterial repetitive intergenic consensus PCR. The MIC(90) of cefepime was not different in ESBL carriers (range 2-4 mg/L), and was especially low in inducible AmpC producers (0.125 mg/L). More than half of all Enterobacter isolates (n=110; 53%) were partly derepressed or fully inducible AmpC producers. In the absence of cefoxitin, they appeared susceptible or intermediately susceptible to cefazolin (n=8; 9%), cefuroxime (n=75; 81.5%), ceftazidime (n=91; 99%), cefotaxime (n=92; 100%), cefpodoxime (n=75; 81.5%) and cefepime (n=91; 99%). CONCLUSIONS: Susceptibility to third-generation cephalosporins would have been falsely assumed in more than half of all Enterobacter isolates, but ESBL in Enterobacter is currently rare in our institution. Integration of multiple double disc tests into the routine antibiogram seems a reliable approach to screen for emerging resistance mechanisms. Etests did not provide additional information in this study. PMID- 17347179 TI - Antimycobacterial activity of bacteriocins and their complexes with liposomes. AB - OBJECTIVES: Bacteriocins (Bcn) are natural peptides that are secreted by several taxonomically distant bacteria and exert bactericidal activity against other bacterial species. Their capacity to inhibit growth of virulent Mycobacterium tuberculosis H37Rv was evaluated in this study. METHODS: Five different Bcn were isolated and purified from bacterial culture supernatants, their amino acid sequence was determined, and activity against mycobacteria assessed in three different models: in vitro mycobacterial cultures, in vitro infection of mouse macrophages and in vivo high-dose infection of inbred mice. RESULTS: In the in vitro model, four out of five Bcn exhibited stronger antimycobacterial activity than equal concentrations of a widely used anti-TB antibiotic, rifampicin. These Bcn were non-toxic for mouse macrophages at a concentration of 0.1 mg/L (>MIC(90) of these compounds). Pure Bcn did not inhibit mycobacterial growth within murine macrophages when added at 0.01-0.1 mg/L, suggesting that at physiologically tolerable concentrations these molecules do not penetrate through the membrane of eukaryotic cells. However, when administered as a complex with phosphatidylcholine-cardiolipin liposomes, Bcn5 (selected as a model compound due to its cytotoxicity and antimycobacterial activity regular titration curves) demonstrated capacity both to inhibit intracellular growth of M. tuberculosis and to prolong survival of mice in an acute TB model. CONCLUSIONS: Given that the mechanism of Bcn bactericidal activity differs from that of all commonly used antibiotics, their possible involvement in complex TB therapies deserves further study. PMID- 17347180 TI - Effects of propofol vs sevoflurane on arterial oxygenation during one-lung ventilation. AB - BACKGROUND: The inhibitory effect of anaesthetic agents on hypoxic pulmonary vasoconstriction may depend upon their dose, especially when using a volatile agent. The aim of this randomized open study was to compare the effects of sevoflurane and propofol, as primary anaesthetic agents, on oxygenation during one-lung ventilation (OLV), with their administration being adjusted to maintain bispectral index (BIS) values between 40 and 60. METHODS: Eighty patients scheduled for a lobectomy, receiving an epidural mixture of ropivacaine and sufentanil, were randomly assigned to Group S (maintenance with sevoflurane) or Group P (maintenance with propofol). After placement of a double-lumen tube, the lungs were ventilated at an inspiratory fraction of oxygen of 1.0, a tidal volume of 6 ml kg(-1), and 12 bpm. Arterial blood gas samples were taken as follows: during two-lung ventilation before OLV, and during the first 40 min of OLV. RESULTS: Fifteen patients were excluded (incorrect placement of the tube or BIS outside the desired range). The two groups were comparable in terms of demographic variables, haemodynamic, and BIS levels during the operation. Four patients in each group had a Sp(O2)<90%. Mean of the lowest Pa(O2) was 16.3 (7.5) kPa in Group S and 17.7 (9.3) kPa in Group P (ns). CONCLUSIONS: Sevoflurane and propofol had similar effect on Pa(O2) during OLV when their administration is titrated to maintain BIS between 40 and 60. PMID- 17347181 TI - Influence of the baricity of a local anaesthetic agent on sedation with propofol during spinal anaesthesia. AB - BACKGROUND: This study examined the effect of different levels of spinal anaesthesia, induced by solutions of different baricity but containing the same amount of local anaesthetic agent, on the requirement for sedation with propofol. METHODS: Thirty-six patients undergoing varicose vein surgery under spinal anaesthesia were randomly allocated to receive tetracaine 15 mg in 3 ml of either glucose 5% (hyperbaric) or CSF (isobaric). I.V. propofol was started 5 min after the intrathecal injection and was titrated to maintain a bispectral index (BIS) score of 65-75. The propofol requirements to maintain this range in the two groups were compared every 5 min. RESULTS: The propofol requirement was always lower in the hyperbaric group, with the differences becoming statistically significant 20 min after the intrathecal injection. Total consumption of propofol over the 55 min of the study was also less in the hyperbaric group. CONCLUSION: The known difference in level of spinal anaesthetic block induced by solutions of different baricity, but the same dose of local anaesthetic, was associated with different requirements for propofol sedation as determined by BIS assessment. PMID- 17347182 TI - Distribution of blood flow and ventilation in the lung: gravity is not the only factor. AB - Current textbooks in anaesthesia describe how gravity affects the regional distribution of ventilation and blood flow in the lung, in terms of vertical gradients of pleural pressure and pulmonary vascular pressures. This concept fails to explain some of the clinical features of disturbed lung function. Evidence now suggests that gravity has a less important role in the variation of regional distribution than structural features of the airways and blood vessels. We review more recent studies that used a variety of methods: external radioactive counters, measurements using inhaled and injected particles, and computer tomography scans. These give a higher spatial resolution of regional blood flow and ventilation. The matching between ventilation and blood flow in these small units of lung is considered; the effects of microgravity, increased gravity, and different postures are reviewed, and the application of these findings to conditions such as acute lung injury is discussed. Down to the scale of the acinus, there is considerable heterogeneity in the distribution of both ventilation and blood flow. However, the matching of blood flow with ventilation is well maintained and may result from a common pattern of asymmetric branching of the airways and blood vessels. Disruption of this pattern may explain impaired gas exchange after acute lung injury and explain how the prone position improves gas exchange. PMID- 17347183 TI - Transoesophageal echocardiography for the detection and quantification of pleural fluid in cardiac surgical patients. AB - BACKGROUND: Transoesophageal echocardiography (TOE) can image pleural fluid. Left pleural collections may be easier to detect than right, as the thoracic aorta serves as an acoustic window. Attempts to quantify pleural fluid using TOE are restricted to a case report in which volume was predicted by multiplying maximal cross-sectional area (CSA(max)) by axial length (AL). A computed tomography (CT) derived formula for quantifying pleural effusions is maximal effusion depth squared (d2) multiplied by maximal effusion length. METHODS: Eight patients were studied before chest closure following coronary bypass surgery. Fifty millilitre saline aliquots were instilled into the pleural space until detected by TOE. Saline was then instilled up to the next 200 ml increment and further 200 ml aliquots added until it spilled from the pleural space. CSA(max), d and AL were measured for each stage and used to calculate pleural fluid volume. RESULTS: Median detection volume (range) was 125 ml (50-200) on the left and 225 ml (150 300) on the right (P = 0.016). Volume calculated by CSA(max) x AL correlated strongly with actual volume (r2 = 0.93 left and 0.92 right) as did volume calculated by d2 x AL (r2 = 0.86 left and 0.89 right). Mean difference between volume calculated by CSA(max) x AL and actual volume was - 51 ml on the left and 45 ml on the right vs - 253 ml on the left and - 212 ml on the right for volume calculated by d2 x AL. CONCLUSIONS: TOE detects small volumes of pleural fluid on both sides of the chest. CSA(max) x AL provides a reasonably accurate measure of pleural fluid volume. PMID- 17347184 TI - Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1). AB - Sugammadex is the first selective relaxant binding agent and reverses rocuronium induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and efficient recovery from profound neuromuscular block was achieved and no adverse events or other safety concerns were reported. PMID- 17347185 TI - Effect of intravenous vasopressor on spread of spinal anaesthesia and fetal acid base equilibrium. AB - BACKGROUND: We previously found rostral spread of spinal plain levobupivacaine to be less with prophylactic i.v. phenylephrine than with ephedrine during Caesarean delivery. This study investigated whether rostral spread of spinal hyperbaric bupivacaine is also less with phenylephrine than with ephedrine. METHODS: The study was randomized and double blind. It compared phenylephrine 100 microg ml-1 (phenylephrine group, n=27), and ephedrine 4.5 mg ml-1 (ephedrine group, n=27), given by infusion during spinal anaesthesia for Caesarean delivery. Block height was assessed to cold and light touch sensation at 15, 30, 60, and 90-min after the spinal injection of 2.8 ml of hyperbaric 0.5% w/v bupivacaine, combined with 0.4 ml diamorphine (1 mg ml-1). Umbilical blood gas values were monitored during the study. RESULTS: Block height was similar for both groups at all of the assessment times. Umbilical artery pH was higher with phenylephrine [median 7.32 (IQR 7.28-7.34)] than with ephedrine [7.20 (7.10-7.28)] (P<0.0001). There was a strong negative correlation between umbilical artery pH and spinal-delivery interval, but only with ephedrine: phenylephrine group, r2=0.09 (P=0.17), and ephedrine group, r2=0.53 (P<0.0001). Five-minute Apgar scores were higher with phenylephrine [10 (9-10)] than ephedrine [9 (9-9)] (P=0.009). CONCLUSIONS: In contrast to its effect on spinal plain levobupivacaine, we did not find rostral spread of spinal hyperbaric bupivacaine to be less with prophylactic phenylephrine than with ephedrine. We observed an unexpectedly high incidence of fetal acidosis with ephedrine and found evidence that longer spinal-delivery intervals increase the risk of fetal acidosis developing with ephedrine, but not phenylephrine. PMID- 17347186 TI - Literature review: health-related quality of life measurement in pediatric oncology: hearing the voices of the children. AB - OBJECTIVES: The objective of this literature review is to provide an overview of the evidence for pediatric patient self-report in pediatric oncology. Methods A review of the general literature on pediatric health-related quality of life (HRQOL) measurement as background, with pediatric patient self-report data from the Journal of Pediatric Psychology during the past 5 years in pediatric oncology summarized. Utilizing the PedsQL available at (http://www.pedsql.org), data are presented to illustrate child and parent reports in pediatric oncology. Results Data demonstrate that children as young as 5 years of age can reliably and validly self-report their HRQOL when an age-appropriate instrument is utilized. Conclusions The evidence supports including pediatric patients' perspectives in clinical trials. Parent proxy-report is recommended when pediatric patients are too young, too cognitively impaired, too ill or fatigued to complete a HRQOL instrument, but not as a substitute for child self-report when the child is willing and able to provide their perspective. PMID- 17347187 TI - Tonsillectomy versus watchful waiting in recurrent streptococcal pharyngitis in adults: randomised controlled trial. AB - OBJECTIVE: To determine the short term efficacy and safety of tonsillectomy for recurrent streptococcal pharyngitis in adults. Design Randomised controlled trial. SETTING: Academic referral centre in Finland. PARTICIPANTS: 70 adults with documented recurrent episodes of streptococcal group A pharyngitis. INTERVENTION: Instant tonsillectomy (n=36) or remaining on waiting list as control (n=34). MAIN OUTCOME MEASURES: Percentage change in the risk of an episode of streptococcal pharyngitis at 90 days. Rates of all episodes of pharyngitis and days with symptoms and adverse effects. RESULTS: The mean (SD) follow-up was 164 (63) days in the control group and 170 (12) days in the tonsillectomy group. At 90 days, streptococcal pharyngitis had recurred in 24% (8/34) in the control group and 3% (1/36) in the tonsillectomy group (difference 21%; 95% confidence interval 6% to 36%). The number needed to undergo tonsillectomy to prevent one recurrence was 5 (3 to 16). During the whole follow-up, the rates of other episodes of pharyngitis and days with throat pain and fever were significantly lower in the tonsillectomy group than in the control group. The most common morbidity related to tonsillectomy was postoperative throat pain (mean length 13 days, SD 4). CONCLUSIONS: Adults with a history of documented recurrent episodes of streptococcal pharyngitis were less likely to have further streptococcal or other throat infections or days with throat pain if they had their tonsils removed. TRIAL REGISTRATION: Clinical Trials NCT00136877. PMID- 17347188 TI - Radioiodine treatment of hyperthyroidism. PMID- 17347189 TI - Exercise in survivors of cancer. PMID- 17347190 TI - Researching a good death. PMID- 17347191 TI - Ratio of boys to girls at birth. PMID- 17347192 TI - Infant feeding and HIV. PMID- 17347193 TI - Stop ambiguous messages on malaria diagnosis. PMID- 17347196 TI - Support from the United States. PMID- 17347197 TI - English classes are being cut. PMID- 17347198 TI - Let's talk about critical consciousness. PMID- 17347199 TI - UK recommendations for severe malaria are worrying. PMID- 17347200 TI - Time for a scientific social network. PMID- 17347201 TI - Academic medicine. Who should call the tune? PMID- 17347202 TI - Academic medicine. UK response. PMID- 17347203 TI - Academia needs to acknowledge the needs of trainees. PMID- 17347204 TI - Thwarted by bureaucracy. PMID- 17347205 TI - Hospital doctors will get below inflation pay increase, while GPs get nothing. PMID- 17347206 TI - Former FDA commissioner is fined 90,000 dollars for failing to disclose conflicts of interest. PMID- 17347209 TI - UK report proposes a new harms index to rate dangers of drugs and alcohol. PMID- 17347213 TI - UK may allow creation of "cybrids" for stem cell research. PMID- 17347214 TI - Dutch inspectors slam standards of preoperative care. PMID- 17347215 TI - University medical school accepts tobacco company funding. PMID- 17347216 TI - Heathrow doctor's case at GMC will be heard in private. PMID- 17347217 TI - US public service advertising could learn from the UK. PMID- 17347218 TI - Polish politicians argue over right to expel sick foreigners. PMID- 17347223 TI - Heart group's approval of fast food meals angers critics. PMID- 17347232 TI - Kidneys on demand. PMID- 17347233 TI - Should NICE evaluate complementary and alternative medicine? PMID- 17347234 TI - Should NICE evaluate complementary and alternative medicines? PMID- 17347235 TI - How specialist training reform sparked crisis of confidence. PMID- 17347237 TI - My illness, my record. PMID- 17347238 TI - Getting services right for those sick enough to die. PMID- 17347239 TI - Cervical spondylosis and neck pain. PMID- 17347240 TI - A patient's journey: whooping cough. PMID- 17347241 TI - Dry mouth. PMID- 17347242 TI - Putting the cart before the horse: testing to improve learning. PMID- 17347248 TI - Expression of CatSper family transcripts in the mouse testis during post-natal development and human ejaculated spermatozoa: relationship to sperm motility. AB - CatSper is a unique sperm cation channel-like protein family exclusively expressed in the testis and plays important roles in sperm functions. The temporal expression profiles of CatSper1-4 mRNAs in the mouse testis during post natal development through adulthood were investigated using real-time RT-PCR. The CatSper2 transcript was present in the testis of the 8-day-old mice, and was repressed in the adult testis after two sharp up-regulations at day 18 and 35. CatSper1 and CatSper3, 4 mRNAs were detectable in the testis of 18-day and 15-day old mice, respectively. After sharp up-regulation at day 25 and 35, respectively, they were maximal at the adult testis stage. The differences between the temporal expression profiles of the CatSper transcripts in post-natal mouse testis development suggest different regulation to their transcription, and potentially contribute to the possibility of forming heteromeric channels among these four CatSper family members. CatSper1-3 transcripts were identified to be present in the human ejaculated spermatozoa by RT-PCR. Significantly higher levels of CatSper2 and CatSper3 mRNAs revealed by real-time RT-PCR were observed in the high-motile spermatozoa than in the low-motile fraction and suggests that CatSper2 and CatSper3 transcripts in the human ejaculated spermatozoa could be the potential targets for further study and male infertility screening. PMID- 17347249 TI - Convergence of male and female lung cancer mortality at younger ages in the European Union and Russia. AB - BACKGROUND: Lung cancer epidemics emerged first among males in European countries in the first half of the 20th century and then among females in the second half. We have explored the recent convergence in sex ratios. METHODS: Age-standardized (world standard) lung cancer mortality rates at ages 20 to 44 years were derived from WHO for 26 countries separately from the beginning of their data series to 2002. The most recent periods in which trends could be adequately represented as linear were determined using the software package 'Joinpoint'. Countries were classified by their statistically significant trends for each sex in these periods. RESULTS: Lung cancer mortality among young adult males tended to decrease. Among females there were significant recent increases in eight ('Pattern 1') countries and no significant trend in 16 ('Pattern 2') countries. Rates decreased in both sexes in the UK and rose in both sexes in Portugal. The extent to which sex ratios had actually converged by 2002 varied widely, with values still above 3 in six eastern countries and below 1 in Scandinavia, the Netherlands and Ireland. CONCLUSION: At the beginning of 21st century, there is a general tendency for sex ratios for lung cancer mortality to converge towards 1, but with considerable variation in the extent to which such convergence has been realized. PMID- 17347251 TI - Autosomal recessive axonal Charcot-Marie-Tooth disease (ARCMT2): phenotype genotype correlations in 13 Moroccan families. AB - Charcot-Marie-Tooth disease is a genetically heterogeneous group of hereditary motor and sensory neuropathies. Three loci for the axonal autosomal recessive subgroup (ARCMT2) have been reported in 1q21 (CMT2B1, LMNA), 8q21 (CMT4A and CMT2K, GDAP1) and 19q13 (CMT2B2). We report here a clinical, electrophysiological, pathological and genetic study in 13 Moroccan families with ARCMT2 phenotypes. Clinical and electrophysiological examinations were performed in all index cases and 64 'at-risk' relatives. Thirty-one patients were clinically affected. A peroneal nerve biopsy was obtained from three patients. Four families were linked to the 1q21 locus, all had the LMNA R298C mutation. Six families were linked to the 8q21 locus, all had the GDAP1 S194X mutation. Founder effects for both mutations were suggested by the analysis of microsatellite markers close to the genes. The three remaining families were excluded from the three known loci. The electrophysiological findings were consistent with an axonal neuropathy. The clinical data show that in CMT2B1 the disease began most often in the second decade and progressed gradually from distal to proximal muscles. Three of our patients with the longest disease durations (>24 years) had also severe impairment in the scapular muscles. Reported here for the first time, this might be a hallmark of CMT2B1. Patients with CMT4A/2K had onset most often before the age of 2 years. Most had severe clubfoot from the beginning, one of the hallmarks of CMT4A/2K. None of our patients with CMT4A/2K had vocal cord paralysis. The clinical phenotype of the three families that are not linked to the three known loci presented some particularities that were not seen in those with known genetic defects. One family was characterized by late onset of the disease (>20 years) or a mild neuropathy that was diagnosed only when the family was examined. In a second family, dorsal scoliosis was the most prominent symptom. In the third family, symptoms began in the second decade with a moderate neuropathy associated with a pronounced scoliosis. These families illustrate the extent of clinical and genetic heterogeneity in ARCMT2. PMID- 17347250 TI - Rates of cerebral atrophy differ in different degenerative pathologies. AB - Neurodegenerative disorders are pathologically characterized by the deposition of abnormal proteins in the brain. It is likely that future treatment trials will target the underlying protein biochemistry and it is therefore increasingly important to be able to distinguish between different pathologies during life. The aim of this study was to determine whether rates of brain atrophy differ in neurodegenerative dementias that vary by pathological diagnoses and characteristic protein biochemistry. Fifty-six autopsied subjects were identified with a clinical diagnosis of dementia and two serial head MRI. Subjects were subdivided based on pathological diagnoses into Alzheimer's disease, dementia with Lewy bodies (DLB), mixed Alzheimer's disease/DLB, frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes (FTLD-U), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Twenty-five controls were matched by age, gender and scan interval, to the study cohort. The boundary shift integral was used to calculate change over time in whole brain (BBSI) and ventricular volume (VBSI). All BSI results were annualized by adjusting for scan interval. The rates of whole brain atrophy and ventricular expansion were significantly increased compared to controls in the Alzheimer's disease, mixed Alzheimer's disease/DLB, FTLD-U, CBD and PSP groups. However, atrophy rates in the DLB group were not significantly different from control rates of atrophy. The largest rates of atrophy were observed in the CBD group which had a BBSI of 2.3% and VBSI of 16.2%. The CBD group had significantly greater rates of BBSI and VBSI than the DLB, mixed Alzheimer's disease/DLB, Alzheimer's disease and PSP groups, with a similar trend observed when compared to the FTLD-U group. The FTLD-U group showed the next largest rates with a BBSI of 1.7% and VBSI of 9.6% which were both significantly greater than the DLB group. There was no significant difference in the rates of atrophy between the Alzheimer's disease, mixed Alzheimer's disease/DLB and PSP groups, which all showed similar rates of atrophy; BBSI of 1.1, 1.3 and 1.0% and VBSI of 8.3, 7.2 and 10.9%, respectively. Rates of atrophy therefore differ according to the pathological diagnoses and underlying protein biochemistry. While rates are unlikely to be useful in differentiating Alzheimer's disease from cases with mixed Alzheimer's disease/DLB pathology, they demonstrate important pathophysiological differences between DLB and those with mixed Alzheimer's disease/DLB and Alzheimer's disease pathology, and between those with CBD and PSP pathology. PMID- 17347252 TI - Endogenous dynorphin in epileptogenesis and epilepsy: anticonvulsant net effect via kappa opioid receptors. AB - Neuropsychiatric disorders are one of the main challenges of human medicine with epilepsy being one of the most common serious disorders of the brain. Increasing evidence suggest neuropeptides, particularly the opioids, play an important role in epilepsy. However, little is known about the mechanisms of the endogenous opioid system in epileptogenesis and epilepsy. Therefore, we investigated the role of endogenous prodynorphin-derived peptides in epileptogenesis, acute seizure behaviour and epilepsy in prodynorphin-deficient mice. Compared with wild type littermates, prodynorphin knockout mice displayed a significantly reduced seizure threshold as assessed by tail-vein infusion of the GABA(A) antagonist pentylenetetrazole. This phenotype could be entirely rescued by the kappa receptor-specific agonist U-50488, but not by the mu receptor-specific agonist DAMGO. The delta-specific agonist SNC80 decreased seizure threshold in both genotypes, wild-type and knockout. Pre-treatment with the kappa selective antagonist GNTI completely blocked the rescue effect of U-50488. Consistent with the reduced seizure threshold, prodynorphin knockout mice showed faster seizure onset and a prolonged time of seizure activity after intracisternal injection of kainic acid. Three weeks after local injection of kainic acid into the stratum radiatum CA1 of the dorsal hippocampus, prodynorphin knockout mice displayed an increased extent of granule cell layer dispersion and neuronal loss along the rostrocaudal axis of the ipsi- and partially also of the contralateral hippocampus. In the classical pentylenetetrazole kindling model, dynorphin deficient mice showed significantly faster kindling progression with six out of eight animals displaying clonic seizures, while none of the nine wild-types exceeded rating 3 (forelimb clonus). Taken together, our data strongly support a critical role for dynorphin in the regulation of hippocampal excitability, indicating an anticonvulsant role of kappa opioid receptors, thereby providing a potential target for antiepileptic drugs. PMID- 17347254 TI - Mutations in SUCLA2: a tandem ride back to the Krebs cycle. PMID- 17347255 TI - Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight. AB - Very low birth weight (VLBW) children are at high risk of perinatal white matter injury, which, when subtle, may not be seen using conventional magnetic resonance imaging. The relationship between clinical findings and fractional anisotropy (FA) measurements in white matter of adolescents born prematurely with VLBW was studied in 34 subjects (age = 15 years, birth weight left, Type II, III: left > right, chi2 = 6.41, P = 0.041). For schizophrenics, the distribution differed significantly from controls (chi2 = 11.90, P = 0.003), especially in the right hemisphere (chi2 = 13.67, P = 0.001). Moreover, the asymmetry observed in controls was not present in schizophrenia (chi2 = 0.13, P = 0.94). Specifically, the most frequent Type I expression was decreased and the rarest Type III expression was increased in schizophrenia, relative to controls. Furthermore, patients with Type III expression in any hemisphere evinced poorer socioeconomic status, poorer cognitive function, more severe symptoms and impulsivity, compared to patients without Type III expression. In contrast, patients with Type I in any hemisphere showed better cognitive function and milder symptoms compared to patients without Type I. Structurally, patients with Type III had significantly smaller intra cranial contents (ICC) volumes than did patients without Type III (t(40) = 2.29, P = 0.027). The present study provides evidence of altered distribution of orbitofrontal sulcogyral pattern in schizophrenia, possibly reflecting a neurodevelopmental aberration in schizophrenia. Such altered sulcogyral pattern is unlikely to be due to secondary effects of the illness such as medication. Moreover, the structural association between Type III and small ICC volume, observed in the patient group, may suggest that Type III expression could be part of a systematic neurodevelopmental alteration, given that the small ICC volume could reflect early reduction of cranial growth driven by brain growth. The observed contrasting association of Type III expression with poorer outcome, and that of Type I expression with better outcome, further suggests clinical heterogeneity, and possible differences in treatment responsiveness in schizophrenia. PMID- 17347257 TI - Loss of insight in frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy. AB - Loss of insight is one of the core features of frontal/behavioural variant frontotemporal dementia (FTD). FTD shares many clinical and pathological features with corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). The aim of this study was to investigate awareness of cognitive deficits in FTD, CBD and PSP using a multidimensional approach to assessment, which examines metacognitive knowledge of the disorders, online monitoring of errors (emergent awareness) and ability to accurately predict performance on future tasks (anticipatory awareness). Thirty-five patients (14 FTD, 11 CBD and 10 PSP) and 20 controls were recruited. Results indicated that loss of insight was a feature of each of the three patient groups. FTD patients were most impaired on online monitoring of errors compared to the other two patient groups. Linear regression analysis demonstrated that different patterns of neuropsychological performance and behavioural rating scores predicted insight deficits across the three putative awareness categories. Furthermore, higher levels of depression were associated with poor anticipatory awareness, reduced empathy was related to impaired metacognitive awareness and impaired recognition of emotional expression in faces was associated with both metacognitive and anticipatory awareness deficits. The results are discussed in terms of neurocognitive models of awareness and different patterns of neurobiological decline in the separate patient groups. PMID- 17347258 TI - The spectrum of SCN1A-related infantile epileptic encephalopathies. AB - The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders. PMID- 17347259 TI - Local control in thin filament activation of cardiac muscle. PMID- 17347260 TI - Nitroxyl effects on myocardium provide new insights into the significance of altered myofilament response to calcium in the regulation of contractility. PMID- 17347261 TI - The magic mountain or death in Venice: chronic hypoxia may alleviate oxidative stress in the kidney. PMID- 17347263 TI - Susceptibility for homeostatic plasticity is down-regulated in parallel with maturation of the rat hippocampal synaptic circuitry. AB - Homeostatic regulation, i.e. the ability of neurons and neuronal networks to adjust their output in response to chronic alterations in electrical activity is a prerequisite for the pronounced functional plasticity in the developing brain. Cellular mechanisms of homeostatic plasticity have mainly been studied in cultured preparations. To understand the developmental time frame and properties of homeostatic plasticity under more physiological conditions, we have here compared the effects of activity deprivation on synaptic transmission in acutely isolated and cultured hippocampal slices at different stages of development. We find that transmission at both glutamatergic and GABAergic synapses is strongly and rapidly (15 h) regulated in the opposite directions in response to inactivity during narrow, separated time windows early in development. Following this critical period of synaptic development, induction of the homeostatic response requires longer periods (40 h) of inactivity. At glutamatergic synapses, activity blockade led to an increase in the amplitude and frequency of mEPSCs, and the threshold for induction of this response was increased during development. In contrast, homeostatic regulation at GABAergic synapses was expressed in a qualitatively distinct manner at different developmental stages. Immature neurons responded rapidly to inactivity by regulating mIPSC frequency, while longer activity blockade led to a decrease in the mIPSC amplitude independent of the neuronal maturation. The susceptibility of immature networks to homeostatic regulation may serve as a safety mechanism against rapid runaway destability during the time of intense remodelling of the synaptic circuitry. PMID- 17347262 TI - Response profiles to amino acid odorants of olfactory glomeruli in larval Xenopus laevis. AB - Glomeruli in the vertebrate olfactory bulb (OB) appear as anatomically discrete modules receiving direct input from the olfactory epithelium (OE) via axons of olfactory receptor neurons (ORNs). The response profiles with respect to amino acids (AAs) of a large number of ORNs in larval Xenopus laevis have been recently determined and analysed. Here we report on Ca(2+) imaging experiments in a nose brain preparation of the same species at the same developmental stages. We recorded responses to AAs of glomeruli in the OB and determined the response profiles to AAs of individual glomeruli. We describe the general features of AA responsive glomeruli and compare their response profiles to AAs with those of ORNs obtained in our previous study. A large number of past studies have focused either on odorant responses in the OE or on odorant-induced responses in the OB. However, a thorough comparison of odorant-induced responses of both stages, ORNs and glomeruli of the same species is as yet lacking. The glomerular response profiles reported herein markedly differ from the previously obtained response profiles of ORNs in that glomeruli clearly have narrower selectivity profiles than ORNs. We discuss possible explanations for the different selectivity profiles of glomeruli and ORNs in the context of the development of the olfactory map. PMID- 17347264 TI - Activity-dependent changes in temporal components of neurotransmission at the juvenile mouse calyx of Held synapse. AB - The temporal fidelity of synaptic transmission is constrained by the reproducibility of time delays such as axonal conduction delay and synaptic delay, but very little is known about the modulation of these distinct components. In particular, synaptic delay is not generally considered to be modifiable under physiological conditions. Using simultaneous paired patch-clamp recordings from pre- and postsynaptic elements of the calyx of Held synapse, in juvenile mouse auditory brainstem slices, we show here that synaptic activity (20 200 Hz) leads to activity-dependent increases in synaptic delay and its variance as well as desynchronization of evoked responses. Such changes were most robust at 200 Hz in 2 mM extracellular Ca(2+) ([Ca(2+)](o)), and could be attenuated by lowering [Ca(2+)](o) to 1 mM, increasing temperature to 35 degrees C, or application of the GABA(B)R agonist baclofen, which inhibits presynaptic Ca(2+) currents (I(Ca)). Conduction delay also exhibited slight activity-dependent prolongation, but this prolongation was only sensitive to temperature, and not to [Ca(2+)](o) or baclofen. Direct voltage-clamp recordings of I(Ca) evoked by repeated action potential train template (200 Hz) revealed little jitter in the timing and kinetics of I(Ca) under various conditions, suggesting that increases in synaptic delay and its variance occur downstream of Ca(2+) entry. Loading the Ca(2+) chelator EGTA-AM into terminals reduced the progression rate, the extent of activity-dependent increases in various delay components, and their variance, implying that residual Ca(2+) accumulation in the presynaptic nerve terminal induces these changes. Finally, by applying a test pulse at different intervals following a 200 Hz train (150 ms), we demonstrated that prolongation in the various delay components reverses in parallel with recovery in synaptic strength. These observations suggest that a depletion of the readily releasable pool of SVs during high-frequency activity may downregulate not only synaptic strength but also decrease the temporal fidelity of neurotransmission at this and other central synapses. PMID- 17347266 TI - Multi-tasking in the spinal cord--do 'sympathetic' interneurones work harder than we give them credit for? AB - The role of interneurones in the control of sympathetic activity has been somewhat of a mystery since, for many years, it was difficult to target these cells for study. Recently scientists have started to unravel the action potential properties of these neurones, where they receive their inputs from and where they project to. This review looks at the information known to date about sympathetic interneurones. The locations of these neurones and their local axonal ramifications suggest that they play a more widespread function than previously thought. Therefore the data to support such a theory are also examined. PMID- 17347265 TI - The emergence of proteinase-activated receptor-2 as a novel target for the treatment of inflammation-related CNS disorders. AB - The signalling molecules that are involved in inflammatory pathways are now thought to play a part in many disorders of the central nervous system (CNS). In common with peripheral chronic inflammatory diseases such a rheumatoid arthritis and ulcerative colitis, evidence now exists for the involvement of inflammatory cytokines, for example tumour necrosis factor (TNF) and interleukins (IL), in neurological disorders. A common factor observed with the up-regulation of these cytokines in peripheral inflammatory diseases, is the increased expression of the proteinase-activated receptor (PAR) subtype PAR-2. Indeed, recent evidence suggests that targeting PAR-2 helps reduce joint swelling observed in animal models of arthritis. So could targeting this receptor prove to be useful in treating those CNS disorders where inflammatory processes are thought to play an intrinsic role? The aim of this review is to summarize the emerging data regarding the role of PAR-2 in neuroinflammation and ischaemic injury and discuss its potential as an exciting new target for the prevention and/or treatment of CNS disorders. PMID- 17347267 TI - Plasma membrane delivery, endocytosis and turnover of transcobalamin receptor in polarized human intestinal epithelial cells. AB - Cells that are metabolically active and in a high degree of differentiation and proliferation require cobalamin (Cbl: vitamin B(12)) and they obtain it from the circulation bound to transcobalamin (TC) via the transcobalamin receptor (TC-R). This study has investigated the plasma membrane dynamics of TC-R expression in polarized human intestinal epithelial Caco-2 cells using techniques of pulse chase labelling, domain-specific biotinylation and cell fractionation. Endogenously synthesized TC-R turned over with a half-life (T(1/2)) of 8 h following its delivery to the basolateral plasma membrane (BLM). The T(1/2) of BLM delivery was 15 min and TC-R delivered to the BLM was endocytosed and subsequently degraded by leupeptin-sensitive proteases. However, about 15% of TC R endocytosed from the BLM was transcytosed (T(1/2), 45 min) to the apical membranes (BBM) where it underwent endocytosis and was degraded. TC-R delivery to both BLM and BBM was inhibited by Brefeldin A and tunicamycin, but not by wortmannin or leupeptin. Colchicine inhibited TC-R delivery to BBM, but not BLM. At steady state, apical TC-R was associated with megalin and both these proteins were enriched in an intracellular compartment which also contained Rab5 and transferrin receptor. These results indicate that following rapid delivery to both plasma membrane domains of Caco-2 cells, TC-R undergoes constitutive endocytosis and degradation by leupeptin-sensitive proteases. TC-R expressed in apical BBM complexes with megalin during its transcytosis from the BLM. PMID- 17347268 TI - Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K+. AB - During strenuous exercise, extracellular K(+) ([K(+)](o)) is increased, which potentially can reduce muscle excitability and force production. In addition, exercise leads to accumulation of lactate and H(+) and increased levels of circulating catecholamines. Individually, reduced pH and increased catecholamines have been shown to counteract the depressing effect of elevated K(+). This study examines (i) whether the effects of addition of lactic acid and adrenaline on the excitability of isolated muscles are caused by separate mechanisms and are additive and (ii) whether the effect of adding lactic acid or increasing CO(2) is related to a reduction of intra- or extracellular pH. Rat soleus muscles were incubated at a [K(+)](o) of 15 mM, which reduced tetanic force by 85%. Subsequent addition of 20 mM lactic acid or 10(-5) M adrenaline led to a small recovery of force, but when added together induced an almost complete force recovery. Compound action potentials showed that the force recovery was associated with recovery of muscle excitability. The improved excitability after addition of adrenaline was associated with increased Na(+)-K(+) pump activity resulting in hyperpolarization and an increase in the chemical Na(+) gradient. In contrast, addition of lactic acid had no effect on the membrane potential or the Na(+)-K(+) pump activity, but most likely increased excitability via a reduction in intracellular pH. It is concluded that the protective effects of acidosis and adrenaline on muscle excitability and force took place via different mechanisms and were additive. The results suggest that circulating catecholamines and development of acidosis during exercise may improve the tolerance of muscles to elevated [K(+)](o). PMID- 17347269 TI - Up-regulation of arginase activity contributes to attenuated reflex cutaneous vasodilatation in hypertensive humans. AB - Reflex cutaneous vasodilatation is dependent on nitric oxide (NO), which is diminished in hypertension (HTN). Arginase may be up-regulated with HTN, which preferentially metabolizes L-arginine (L-arg), competing with NO-synthase (NOS) mediated pathways and limiting NO synthesis. We hypothesized that NO-dependent vasodilatation would be attenuated in HTN skin, and arginase inhibition (A-I) alone or with concurrent l-arginine supplementation, would augment vasodilatation. Five microdialysis fibres were placed in skin of eight unmedicated subjects with HTN (mean arterial pressure (MAP), 112 +/- 1 mmHg) and nine age-matched normotensive (AMN) (MAP: 87 +/- 1 mmHg) men and women to serve as: control (C, Ringer solution), NOS inhibited (NOS-I, 10 mM L-NAME), A-I (5 mM BEC + 5 mM nor-NOHA), L-arg supplemented (L-arg, 10 mM L-arg), and combined A-I + L-arg. Reflex vasodilatation was induced by using a water-perfused suit to increase oral temperature (T(or)) 1.0 degrees C. Red cell flux was measured by laser-Doppler flowmetry over each site. Cutaneous vascular conductance was calculated (CVC = flux/MAP) and normalized to maximal CVC (28 mM SNP + local heating to 43 degrees C). The Delta%CVC(max) between the control and NOS-I site was calculated as the difference between C and NOS-I sites. Maximal CVC was attenuated in the HTN subjects by approximately 25% compared with AMN subjects (P<0.001). Throughout, whole body heating %CVC(max) was not different between the groups (HTN, 43 +/- 3%CVC(max) versus AMN, 45 +/- 3%CVC(max), P>0.05). NOS-I significantly decreased %CVC(max) in both groups but %CVC(max) was greater in the HTN group (HTN, 32 +/- 4%CVC(max) versus AMN, 23 +/- 3%CVC(max), P<0.05). The Delta%CVC(max) between the control and NOS-I sites was attenuated at DeltaT(or) > 0.5 degrees C in the HTN group (P < 0.001 versus AMN). A-I alone augmented %CVC(max) only in the HTN group (HTN, 65 +/- 5%CVC(max) versus AMN, 48 +/- 3%CVC(max), P<0.05). L-Arg alone did not affect %CVC(max) in either group (HTN, 49 +/- 5%CVC(max) versus AMN, 49 +/- 3%CVC(max), P > 0.05). Combined A-I + L-arg augmented %CVC(max) in both subject groups compared with their respective control sites (HTN, 60 +/- 7%CVC(max) versus AMN, 61 +/- 3%CVC(max), both P<0.05 versus respective control sites). Vasodilatation is attenuated with HTN due to decreased NO-dependent vasodilatation and can be augmented with arginase inhibition but not L-arg supplementation, suggesting that arginase is up-regulated with HTN. PMID- 17347270 TI - Mechanosensitive activation of K+ channel via phospholipase C-induced depletion of phosphatidylinositol 4,5-bisphosphate in B lymphocytes. AB - In various types of cells mechanical stimulation of the plasma membrane activates phospholipase C (PLC). However, the regulation of ion channels via mechanosensitive degradation of phosphatidylinositol 4,5-bisphosphate (PIP(2)) is not known yet. The mouse B cells express large conductance background K(+) channels (LK(bg)) that are inhibited by PIP(2). In inside-out patch clamp studies, the application of MgATP (1 mm) also inhibited LK(bg) due to the generation of PIP(2) by phosphoinositide (PI)-kinases. In the presence of MgATP, membrane stretch induced by negative pipette pressure activated LK(bg), which was antagonized by PIP(2) (> 1 microm) or higher concentration of MgATP (5 mm). The inhibition by PIP(2) was partially reversible. However, the application of methyl beta-cyclodextrin, a cholesterol scavenger disrupting lipid rafts, induced the full recovery of LK(bg) activity and facilitated the activation by stretch. In cell-attached patches, LK(bg) were activated by hypotonic swelling of B cells as well as by negative pressure. The mechano-activation of LK(bg) was blocked by U73122, a PLC inhibitor. Neither actin depolymerization nor the inhibition of lipid phosphatase blocked the mechanical effects. Direct stimulation of PLC by m 3M3FBS or by cross-linking IgM-type B cell receptors activated LK(bg). Western blot analysis and confocal microscopy showed that the hypotonic swelling of WEHI 231 induces tyrosine phosphorylation of PLCgamma2 and PIP(2) hydrolysis of plasma membrane. The time dependence of PIP(2) hydrolysis and LK(bg) activation were similar. The presence of LK(bg) and their stretch sensitivity were also proven in fresh isolated mice splenic B cells. From the above results, we propose a novel mechanism of stretch-dependent ion channel activation, namely, that the degradation of PIP(2) caused by stretch-activated PLC releases LK(bg) from the tonic inhibition by PIP(2). PMID- 17347271 TI - Sarcomere length dependence of rat skinned cardiac myocyte mechanical properties: dependence on myosin heavy chain. AB - The effects of sarcomere length (SL) on sarcomeric loaded shortening velocity, power output and rates of force development were examined in rat skinned cardiac myocytes that contained either alpha-myosin heavy chain (alpha-MyHC) or beta-MyHC at 12 +/- 1 degrees C. When SL was decreased from 2.3 microm to 2.0 microm submaximal isometric force decreased approximately 40% in both alpha-MyHC and beta-MyHC myocytes while peak absolute power output decreased 55% in alpha-MyHC myocytes and 70% in beta-MyHC myocytes. After normalization for the fall in force, peak power output decreased about twice as much in beta-MyHC as in alpha MyHC myocytes (41% versus 20%). To determine whether the fall in normalized power was due to the lower force levels, [Ca(2+)] was increased at short SL to match force at long SL. Surprisingly, this led to a 32% greater peak normalized power output at short SL compared to long SL in alpha-MyHC myocytes, whereas in beta MyHC myocytes peak normalized power output remained depressed at short SL. The role that interfilament spacing plays in determining SL dependence of power was tested by myocyte compression at short SL. Addition of 2% dextran at short SL decreased myocyte width and increased force to levels obtained at long SL, and increased peak normalized power output to values greater than at long SL in both alpha-MyHC and beta-MyHC myocytes. The rate constant of force development (k(tr)) was also measured and was not different between long and short SL at the same [Ca(2+)] in alpha-MyHC myocytes but was greater at short SL in beta-MyHC myocytes. At short SL with matched force by either dextran or [Ca(2+)], k(tr) was greater than at long SL in both alpha-MyHC and beta-MyHC myocytes. Overall, these results are consistent with the idea that an intrinsic length component increases loaded crossbridge cycling rates at short SL and beta-MyHC myocytes exhibit a greater sarcomere length dependence of power output. PMID- 17347272 TI - Spino-dendritic cross-talk in rodent Purkinje neurons mediated by endogenous Ca2+ binding proteins. AB - The range of actions of the second messenger Ca(2+) is a key determinant of neuronal excitability and plasticity. For dendritic spines, there is on-going debate regarding how diffusional efflux of Ca(2+) affects spine signalling. However, the consequences of spino-dendritic coupling for dendritic Ca(2+) homeostasis and downstream signalling cascades have not been explored to date. We addressed this question by four-dimensional computer simulations, which were based on Ca(2+)-imaging data from mice that either express or lack distinct endogenous Ca(2+)-binding proteins. Our simulations revealed that single active spines do not affect dendritic Ca(2+) signalling. Neighbouring, coactive spines, however, induce sizeable increases in dendritic [Ca(2+)](i) when they process slow synaptic Ca(2+) signals, such as those implicated in the induction of long term plasticity. This spino-dendritic coupling is mediated by buffered diffusion, specifically by diffusing calbindin-bound Ca(2+). This represents a central mechanism for activating calmodulin in dendritic shafts and therefore a novel form of signal integration in spiny dendrites. PMID- 17347273 TI - Inhibition of nitric oxide and prostaglandins, but not endothelial-derived hyperpolarizing factors, reduces blood flow and aerobic energy turnover in the exercising human leg. AB - Prostaglandins, nitric oxide (NO) and endothelial-derived hyperpolarizing factors (EDHFs) are substances that have been proposed to be involved in the regulation of skeletal muscle blood flow during physical activity. We measured haemodynamics, plasma ATP at rest and during one-legged knee-extensor exercise (19 +/- 1 W) in nine healthy subjects with and without intra-arterial infusion of indomethacin (Indo; 621 +/- 17 microg min(-1)), Indo + N(G)-monomethyl-L-arginine (L-NMMA; 12.4 +/- 0.3 mg min(-1)) (double blockade) and Indo + L-NMMA + tetraethylammonium chloride (TEA; 12.4 +/- 0.3 mg min(-1)) (triple blockade). Double and triple blockade lowered leg blood flow (LBF) at rest (P<0.05), while it remained unchanged with Indo. During exercise, LBF and vascular conductance were 2.54 +/- 0.10 l min(-1) and 25 +/- 1 mmHg, respectively, in control and they were lower with double (33 +/- 3 and 36 +/- 4%, respectively) and triple (26 +/- 4 and 28 +/- 3%, respectively) blockade (P<0.05), while there was no difference with Indo. The lower LBF and vascular conductance with double and triple blockade occurred in parallel with a lower O(2) delivery, cardiac output, heart rate and plasma [noradrenaline] (P<0.05), while blood pressure remained unchanged and O(2) extraction and femoral venous plasma [ATP] increased. Despite the increased O(2) extraction, leg was 13 and 17% (triple and double blockade, respectively) lower than control in parallel to a lower femoral venous temperature and lactate release (P<0.05). These results suggest that NO and prostaglandins play important roles in skeletal muscle blood flow regulation during moderate intensity exercise and that EDHFs do not compensate for the impaired formation of NO and prostaglandins. Moreover, inhibition of NO and prostaglandin formation is associated with a lower aerobic energy turnover and increased concentration of vasoactive ATP in plasma. PMID- 17347274 TI - The impact of murine strain and sex on postnatal development after maternal dietary restriction during pregnancy. AB - The objective of this study was to characterize offspring responses to maternal dietary restriction (DR) in two phylogenetically distant strains of mice: A/J and C57BL/6J (B6). Pregnant mice were fed 100% or 70% of ad libitum between 6.5 and 17.5 days (d) gestation. Offspring were fed 100% ad libitum postweaning. All comparisons were made to strain and sex matched controls. Male DR-B6 offspring initially grew slower than controls; however, by 77 d and 182 d they were significantly heavier (P<0.05). Further, they had an increase percentage fat mass (+70%, P<0.01) by 182 d and were glucose intolerant at both 80 d (P<0.001) and 186 d (P<0.05). In contrast, weight, %Fat mass and glucose tolerance in DR-A/J males during postnatal life were not different from controls. Female DR-B6 mice showed catch-up growth during the first 77 d of life; however, their weight, %Fat mass and glucose tolerance were not different from controls at 80 d and 186 d. Although female DR-A/J were heavier than controls at 182 d (P<0.05), their %Fat mass and glucose tolerance were not different from controls at 182 d and 186 d. The observed strain and sex differences offer a unique opportunity to begin to define gene-environment interactions that contribute to developmental origins of health and disease. PMID- 17347276 TI - Intestinal and hepatic metabolism of glutamine and citrulline in humans. AB - Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal-renal pathway involving inter-organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2-(15)N]glutamine and [ureido-(13)C-(2)H(2)]citrulline. Arterial, portal venous and hepatic venous blood were sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans. PMID- 17347275 TI - Auto-inhibition of rat parallel fibre-Purkinje cell synapses by activity dependent adenosine release. AB - Adenosine is an important signalling molecule involved in a large number of physiological functions. In the brain these processes are as diverse as sleep, memory, locomotion and neuroprotection during episodes of ischaemia and hypoxia. Although the actions of adenosine, through cell surface G-protein-coupled receptors, are well characterized, in many cases the sources of adenosine and mechanisms of release have not been defined. Here we demonstrate the activity dependent release of adenosine in the cerebellum using a combination of electrophysiology and biosensors. Short trains of electrical stimuli delivered to the molecular layer in vitro, release adenosine via a process that is both TTX and Ca(2+) sensitive. As ATP release cannot be detected, adenosine must either be released directly or rapidly produced by highly localized and efficient extracellular ATP breakdown. Since adenosine release can be modulated by receptors that act on parallel fibre-Purkinje cell synapses, we suggest that the parallel fibres release adenosine. This activity-dependent adenosine release exerts feedback inhibition of parallel fibre-Purkinje cell transmission. Spike mediated adenosine release from parallel fibres will thus powerfully regulate cerebellar circuit output. PMID- 17347277 TI - Intrathecal cGMP elicits pressor responses and maintains mean blood pressure during haemorrhage in anaesthetized rats. AB - The intracellular second messenger, cyclic guanosine monophosphate (cGMP), a soluble guanylate cyclase (GC) product, is a primary mechanism for the transduction of a nitric oxide (NO)-initiated signal in the central nervous system. NO is produced from L-arginine by neuronal nitric oxide synthase (NOS), which is found in sympathetic preganglionic neurons of the intermediolateral cell column. This suggests the possibility that NO is a modulator of sympathetic nervous activity (SNA) through a cGMP-mediated mechanism. The aim of this study was to determine the effects of intrathecally injected membrane-permeant 8-bromo cGMP and 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of the soluble form of GC, on arterial pressure in urethane anaesthetized (1.4 g kg(-1) I.P.) rats. The effects of intrathecal cGMP and ODQ on haemodynamic responses to haemorrhage were also investigated. Finally, L-arginine, the NO precursor, was also injected intrathecally, alone and in the presence of ODQ. Baseline mean arterial pressure (MAP) increased significantly after intrathecal 8 Br-cGMP injection (10 microl, 1, 3, 10, 30, 100 microm). A dose-effect relationship (1 microm to 100 microm) was also established (EC(50)=6.03 microm). During continuous haemorrhage, MAP was maintained in animals injected with 8-Br cGMP, relative to the control group. Although no change in baseline MAP was observed as a result of intrathecal ODQ injection (10 microl, 100 mM), a greater rate of fall in MAP was observed during haemorrhage. Injecting L-arginine (10, 100, 1000 microm, 10 microl) showed a pressor effect that was consistent with the effect of the downstream messenger, cGMP. Furthermore, its pressor effect was blocked by ODQ pre-administration. The results indicate that cGMP increases blood pressure, and thus suggest that cGMP increases SNA. This supports the hypothesis that the sympathoexcitatory effects of spinal delivery of NO are mediated by a cGMP-dependent mechanism. PMID- 17347278 TI - Cell-type-specific excitatory and inhibitory circuits involving primary afferents in the substantia gelatinosa of the rat spinal dorsal horn in vitro. AB - The substantia gelatinosa (SG) of the spinal dorsal horn shows significant morphological heterogeneity and receives primary afferent input predominantly from A delta- and C-fibres. Despite numerous anatomical and physiological studies, correlation between morphology and functional connectivity, particularly in terms of inhibitory inputs, remains elusive. To compare excitatory and inhibitory synaptic inputs on individual SG neurones with morphology, we performed whole-cell recordings with Neurobiotin-filled-pipettes in horizontal slices from adult rat spinal cord with attached dorsal roots. Based on dendritic arborization patterns, four major cell types were confirmed: islet, central, radial and vertical cells. Dorsal root stimulation revealed that each class was associated with characteristic synaptic inputs. Islet and central cells had monosynaptic excitatory inputs exclusively from C-afferents. Islet cells received primary-afferent-evoked inhibitory inputs only from A delta-fibres, while those of central cells were mediated by both A delta- and C-fibres. In contrast, radial and vertical cells had monosynaptic excitatory inputs from both A delta- and C fibres and inhibitory inputs mediated by both fibre types. We further characterized the neurochemical nature of these inhibitory synaptic inputs. The majority of islet, central and vertical cells exhibited GABAergic inhibitory inputs, while almost all radial cells also possessed glycinergic inputs. The present study demonstrates that SG neurones have distinct patterns of excitatory and inhibitory inputs that are related to their morphology. The neurotransmitters responsible for inhibitory inputs to individual SG neurones are also characteristic for different morphological classes. These results make it possible to identify primary afferent circuits associated with particular types of SG neurone. PMID- 17347279 TI - Rapamycin-induced hypokalaemic nephropathy in a middle-aged hypertensive male. PMID- 17347280 TI - Novel sources of reactive oxygen species in the human body. PMID- 17347281 TI - Receptor for advanced glycation end products--soluble form and gene polymorphisms in chronic haemodialysis patients. AB - BACKGROUND: The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of vascular and inflammatory diseases. The pathological effects mediated via RAGE are physiologically inhibited by soluble RAGE (sRAGE). Our aim was to study sRAGE and RAGE gene polymorphisms in haemodialysis (HD) patients. METHODS: A total of 261 stable HD patients were enrolled in the study and prospectively followed up for 30 months. At the begining of the study, sRAGE inflammatory and nutritional parameters were determined. RAGE polymorphisms were determined in a subgroup of 214 HD patients. A group of 100 healthy controls was used for comparison. RESULTS: In HD patients, sRAGE is elevated in comparison with healthy controls (3427+/-1508 vs 1758+/-637 pg/ml, P<0.001). It correlates negatively with residual diuresis (r=-0.193, P<0.05), with the acute phase reactants fibrinogen (r=-0.174, P<0.05) and orosomucoid (r=-0.135, P<0.05) and with the leucocyte count (r=-0.158, P<0.05). On the other hand, it is not related to the presence of diabetes mellitus, cardiovascular disease, nutritional status and mortality. The highest sRAGE levels are found in -429 CC and 2184 GG polymorphisms of the RAGE gene. The same results as for sRAGE were obtained for endogenous secretory RAGE (esRAGE), which correlated significantly with sRAGE (r=0.88, P<0.001). CONCLUSION: We conclude that in HD patients, sRAGE is increased due to decreased renal function, which is a very strong determinant of sRAGE levels, and is inversely related to inflammation. The highest sRAGE levels are influenced genetically. In our study, sRAGE levels were not related to mortality of HD patients. PMID- 17347282 TI - A cutaneous disease with multisystem involvement: hypomelanosis of Ito may be associated with proteinuria, focal segmental glomerulosclerosis and end-stage renal disease. PMID- 17347283 TI - New strategies in haemodiafiltration (HDF): prospective comparative analysis between on-line mixed HDF and mid-dilution HDF. AB - BACKGROUND: Improvement in the uraemic toxicity profile obtained with the application of convective and mixed dialysis techniques has stimulated the development of more efficient strategies. Our study was a prospective randomized evaluation of the clinical and technical characteristics of two new haemodiafiltration (HDF) strategies, mixed HDF and mid-dilution HDF, which have recently been proposed with the aim of increasing efficiency and safety with respect to the standard traditional HDF infusion modes. METHODS: Ten stable patients on renal replacement therapy (mean age 64.7 +/- 8.2 years) were submitted in randomized sequence to one mid-week session of mid-dilution HDF and one of mixed HDF with trans-membrane pressure feedback control. All sessions were carried out under similar operating conditions and involved monitoring pressure within the internal dialyser compartments and calculating the rheological and hydraulic indexes. Efficiency in removing urea, phosphate and beta2-microglobulin (beta2-m) was tested. RESULTS: In mixed HDF, safer and more effective flux/pressure conditions resulted in better preservation of the hydraulic and solute membrane permeability (mean in vivo ultrafiltration coefficient 36.9 +/- 3.9 vs 20.1 +/- 3.3 ml/h/mmHg) and ensured higher volume exchange (38.7 +/- 4.2 vs 35.3 +/- 6.5 l/session, P = 0.02) and greater efficiency in removing small and middle molecules (mean urea clearance: 274 +/- 42 vs 264 +/- 47 ml/min, P = 0.028; eKt/V: 1.78 +/- 0.22 vs 1.71 +/- 0.26, P = 0.036; mean phosphate clearance: 138 +/- 16 vs 116 +/- 45 ml/min, P = 0.2; mean beta2-m clearance: 81 +/- 13 vs 59 +/- 13 ml/min, P = 0.001). CONCLUSIONS: Mixed HDF was the most efficient technique in the highest range of safe operating conditions. In mid dilution HDF, high pressures generated inside the dialyser compromised membrane permeability and limited the total infusion rate, resulting in an overall reduction in solute removal. PMID- 17347284 TI - Dyslipidaemia as predictor of progressive renal failure and the impact of treatment with atorvastatin. AB - BACKGROUND: In patients with chronic renal disease, other lipid markers than total cholesterol or low density lipoprotein (LDL)-cholesterol are probably more appropriate to detect a potential lipid-related risk for progression to renal failure. Statin therapy might be protective. METHODS: From 1999 to 2001, 177 consecutive patients with renal disease from our out-patient clinic were included and 169 could be followed-up for a mean period of 4.1 years. Seventy-two progressive patients (end-stage chronic renal disease or >5 ml/min/year decrease of creatinine clearance) were compared in 97 patients with stable or slowly progressive disease (<5 ml/min/year decrease). Throughout the study all patients were treated according to nephrology guidelines. Atorvastatin was instituted in patients with elevated LDL-cholesterol (LDL-C) after the baseline determinations RESULTS: Proteinuria, mean arterial pressure and the type of underlying renal disease were independently associated with progressive renal disease. After adjustment for these factors and whether or not statin therapy was started, an increase in plasma apo B concentration was the most predictive lipid parameter for renal failure. An increase in apo B from 0.77 g/l (10th percentile) to 1.77 g/l (90th percentile) was associated with progressive loss of renal function, represented by an odds ratio of 2.63 (95% CI: 1.02-6.76; P = 0.045). Treatment with atorvastatin in the dyslipidaemic patients to lower LDL-C, was also accompanied by a reduction of proteinuria in this group (P < 0.001). The patients who reached the target level for LDL-C of <2.6 mmol/l in response to atorvastatin showed less often progression than patients with higher LDL-C (P = 0.010). CONCLUSIONS: A high apo B at baseline appeared to be the strongest risk factor among various lipid parameters for progression of renal failure during the following years. Atorvastatin, aimed at lowering LDL-C, reduced proteinuria. Renal outcome was better in patients with the lowest LDL-C on treatment. PMID- 17347285 TI - Endometrial stromal tumours of the uterus: a practical approach using conventional morphology and ancillary techniques. AB - Endometrial stromal tumours (ESTs) are diagnosed in most instances by light microscopy. Often, the greatest challenge is to distinguish between the different subtypes of these tumours. Furthermore, a handful of new or relatively new entities have been described in the literature, which may cause problems in the differential diagnosis; highly cellular leiomyoma is the most common. In addition, new antibodies have been developed to help in the distinction of ESTs from their mimics, as there are prognostic and therapeutic implications. A practical approach is provided for the diagnosis of ESTs on the basis of systematic assessment of histological and immunohistochemical parameters, and recent developments related to these tumours are highlighted. PMID- 17347286 TI - Sarcoidosis of the prostate. AB - A 55-year-old African-American man with clinical stage T1c prostate cancer underwent prostatectomy. Non-caseating, epithelioid granulomata adjacent to the anterior fibromuscular stroma were found incidentally. The granulomata included Langhans giant cells with rare conchoidal bodies. The distribution of the granulomata was not that of non-specific granulomatous prostatitis centred around ducts and glands. By immunohistochemistry, the epithelioid cells were positive for angiotensin-converting enzyme. The histological appearance suggested sarcoidosis, which was confirmed by the clinical history. Four years earlier, the patient had been treated for sarcoidosis. PMID- 17347287 TI - Cervical embryonal rhabdomyosarcoma and ovarian Sertoli-Leydig cell tumour: a more than coincidental association of two rare neoplasms? AB - A case in which an embryonal rhabdomyosarcoma of the cervix and an ovarian Sertoli-Leydig cell tumour of intermediate differentiation occurred in a 13-year old girl is described. Although initially considered as a chance association, a review of the literature showed the co-occurrence of these two uncommon neoplasms in three previous cases. The reason for this association, which is thought to be more than coincidental, is not known, although an underlying genetic abnormality is a possibility. The ovarian tumour in this case was characterised by the presence of foci of cells with extremely pleomorphic nuclei, which initially raised the possibility of metastatic rhabdomyosarcoma. These were interpreted as foci of bizarre nuclei within the Sertoli-Leydig cell tumour. PMID- 17347288 TI - Recurrent prostatic stromal sarcoma with massive high-grade prostatic intraepithelial neoplasia. AB - A unique case of prostatic stromal sarcoma (PSS) that recurred in the pelvic cavity with massive high-grade prostatic intraepithelial neoplasia is described. A 52-year-old man who presented with urinary retention underwent a radical cystoprostatectomy. Tumour tissues of the prostate showed an admixture of hyperplastic glands and markedly cellular stroma of spindle cells arranged in a fascicular pattern, and the tumour was diagnosed as PSS. 66 months after the operation, CT scans revealed three recurrent tumours around the bilateral obturator and left fore iliopsoas. The recurrent tumours were biphasic neoplasms, as before, but the epithelial component had grown prominent and manifested overt atypia in a manner resembling high-grade prostatic intraepithelial neoplasia. Our findings suggest that not only the stromal component but also and the epithelial components of PSS may have malignant potential. PMID- 17347289 TI - Where are all the materials articles? PMID- 17347290 TI - Breakages using a unilateral fixed functional appliance: a case report using The Forsus Fatigue Resistant Device. AB - Fixed functional appliances are designed to provide a simple non-compliant solution to orthodontic Class II treatment. Molar correction can be achieved very quickly using these appliances, but the clinician should be wary of unexpected breakages. This case report documents such an occurrence using a unilateral fixed functional appliance. PMID- 17347291 TI - Natural rubber latex allergy: implications for the orthodontist. AB - Natural rubber latex (NRL) allergy can have potentially serious consequences, and reports of orthodontic patients reacting to NRL have increased significantly over recent years. It is therefore important for the orthodontist to know how to manage patients with an NRL allergy and how to deal with possible reactions to NRL. Safe and effective practice depends on recognizing patients who are at risk of NRL allergy, and an awareness of materials and equipment that contain NRL and the availability of suitable NRL-free alternatives. PMID- 17347292 TI - Molar bands for 'precision' bonding of lingual retainers. AB - Bonded retainers have been used principally for long-term retention of treated cases. Various methods of bonding lingual retainers have been described in the literature over the past two decades. However, accurate and passive placement of retainers has always been a matter of concern. This report presents a simple and economical method for accurate and passive placement of bonded lingual retainers that enables the operator to save considerable chair time. PMID- 17347294 TI - Decontamination of orthodontic bands following size determination and cleaning. AB - OBJECTIVE: To measure the effectiveness of ultrasonic cleaning for decontaminating orthodontic molar bands following size determination using a quantitative antibody capture assay technique. DESIGN: A prospective, cross sectional, clinical and laboratory investigation. SETTING: The Orthodontic Department of the Charles Clifford Dental Hospital and the Microbiology Laboratory of the School of Clinical Dentistry, Sheffield. PARTICIPANTS: Thirty two patients about to start orthodontic treatment with fixed orthodontic appliances. METHODS: Four first molar bands were tried in the mouth and then removed. They were randomly assigned either for no decontamination (control) or to be decontaminated in an ultrasonic cleaning bath for 15 minutes (experimental). The bands were placed in a predetermined volume of phosphate buffered saline (PBS) and assayed by enzyme-linked immunosorbent assay (ELISA) for albumin, to detect the presence of blood and amylase, to detect the presence of saliva. RESULTS: Fifty per cent of decontaminated molar bands showed detectable amounts of amylase, albumin or both. The quantity of detectable amylase was significantly reduced on the cleaned compared with uncleaned bands (P = 0.036); however, the reduction in the quantity of albumin was not statistically significant (P = 0.074). CONCLUSIONS: Ultrasonic cleaning for 15 minutes reduces, but does not always eliminate, salivary proteins (amylase) from tried-in bands. It is less effective at removing serum protein (albumin). There is a need, therefore, to investigate effective means of cleaning organic material from orthodontic bands if they are to be adequately sterilized and reused. PMID- 17347295 TI - Patients' expectations of orthodontic treatment: part 2--findings from a questionnaire survey. AB - OBJECTIVE: To describe patients' and their parents' expectations of orthodontic treatment. DESIGN: A questionnaire survey of 100 patients and their primary care givers attending a new patient orthodontic consultant clinic, at a teaching hospital. SETTING: GKT Orthodontic Department, King's College Dental Hospital, London, UK. SUBJECTS: The sample consisted of 100 participants who completed the questionnaire, including 50 patients aged 12-14 years who had been referred to the orthodontic department for treatment. One parent of each patient was also invited to participate. MATERIALS AND METHODS: Participants completed a valid questionnaire measure of orthodontic expectations that was tested for reliability and validity. Descriptive analysis of the responses was undertaken, and comparisons of children's and parents' expectations, in addition to ethnicity, were made. RESULTS: Patients and parents have similar expectations of treatment, with the exception of expectations of duration of orthodontic treatment (P<0.01), having a brace fitted at the initial visit (P<0.05), and restrictions with regard to what one can eat and drink as a result of orthodontic treatment (P<0.05). Among the patient participants, different ethnic groups displayed different expectations of the initial orthodontic assessment visit, the likelihood of wearing headgear, the impact of orthodontic treatment on diet, and the reaction of peers to treatment (P<0.05). For patients, ethnic group differences were reported for expectations regarding the initial visit, headgear and dietary restrictions (P<0.05). CONCLUSIONS: Patients and their parents share similar expectations of orthodontic treatment for most aspects of care, although parents are more realistic in their estimation of the duration of treatment and the initial visit. The expectations of patients differ from those of their parents with regard to dietary and drink restrictions in relation to orthodontic treatment. Ethnicity significantly influences expectations of orthodontic treatment, and this may relate to differences in the patients' and their parents' assessed outcome of care. PMID- 17347296 TI - A survey of the consent practices of specialist orthodontic practitioners in the North-West of England. AB - OBJECTIVE: To use a questionnaire to obtain information on the consent practices of specialist orthodontic practitioners in the North-West of England and highlight any areas for improvement. DESIGN: Postal questionnaire. SETTING: This survey was conducted among specialist practitioners in 2005-2006. SUBJECT AND METHODS: A questionnaire was sent to 84 specialist practitioners on the specialist register in the North-West of England. This consisted of six sections with a mixture of yes/no responses and a section that determined for which subjects consent was obtained and how. OUTCOME: Responses were received from 58 (69%) practitioners. Ten were discounted. RESULTS: Forty-five (94%) of the 48 practitioners who responded routinely obtained consent from patients, and 27 (60%) used a consent form. Of these 27, 16 (59%) forms were based on a recommended design from an organization such as the British Orthodontic Society. Twenty-three (85%) practitioners gave the form to the patient/parent to read themselves, and 24 (89%) got the consent form signed by the patient/parent. Eighteen (67%) forms were countersigned by the orthodontist or an assigned member of staff. Seventeen (63%) practitioners gave the patient a photocopy. Of the 45 respondents who did obtain consent from their patients, seven (16%) practitioners assigned the consent process to a member of staff. Twenty-eight (62%) respondents would allow a patient under 16 to consent to treatment, with the youngest age being 10 years. CONCLUSIONS: Forty-five (94%) specialist practitioners who responded did routinely obtain consent from patients for treatment, but 18 (40%) did not use a consent form. The subjects discussed with the patient varied. Areas for improvement are highlighted. PMID- 17347298 TI - Current products and practice: Tip-Edge Plus. AB - A recent modification to the Tip-Edge bracket system now enables torque and tip corrections to be achieved without the use of auxiliary springs. This article describes the new Tip-Edge Plus. PMID- 17347299 TI - Twin-block re-activation. PMID- 17347301 TI - ATF4 differentially regulates transcriptional activation of myeloid-specific genes by C/EBPepsilon and C/EBPalpha. AB - Dimerization between different basic region leucine zipper (ZIP) transcription factors is regarded as an important mechanism for integrating various extracellular signals to control specific patterns of gene expression in cells. The activating transcription factor 4 (ATF4) protein was identified as a principal partner for the myeloid-specific transcriptional factor C/EBPepsilon. Dimerization required the ZIP motif of each protein and redirected DNA binding of C/EBPepsilon and ATF4 from their respective symmetric consensus sites to asymmetric C/EBP and cAMP response element sites. The C/EBPepsilon:ATF4 heterodimer bound to the C/EBP sites in the promoters of the myeloid-specific genes encoding neutrophil elastase (NE) and the G-CSF receptor (G-CSFR). Also, the heterodimer bound a previously uncharacterized site in the promoter of the mim-1 gene at nucleotide -174. Coexpression of ATF4 and C/EBPepsilon in the presence of c-Myb synergistically activated the mim-1 and NE promoters compared with C/EBPepsilon plus c-Myb alone. Synergistic activation was not observed for the G-CSFR promoter and only occurred in the presence of c-myb with the NE or mim 1 promoters. In contrast, ATF4:C/EBPalpha dimers bound to the C/EBP sites in the G-CSFR and NE promoters, but transcriptional activation was inhibited by 30-80% in the presence or absence of c-Myb. We propose that ATF4 may regulate myeloid gene expression differentially by potentiating C/EBPepsilon but inhibiting C/EBPalpha-mediated transcriptional activation. PMID- 17347302 TI - The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells. AB - The death-associated protein kinase 2 (DAPK2) belongs to a family of Ca(2+)/calmodulin-regulated serine/threonine kinases involved in apoptosis. During investigation of candidate genes operative in granulopoiesis, we identified DAPK2 as highly expressed. Subsequent investigations demonstrated particularly high DAPK2 expression in normal granulocytes compared with monocytes/macrophages and CD34(+) progenitor cells. Moreover, significantly increased DAPK2 mRNA levels were seen when cord blood CD34(+) cells were induced to differentiate toward neutrophils in tissue culture. In addition, all-trans retinoic acid (ATRA)-induced neutrophil differentiation of two leukemic cell lines, NB4 and U937, revealed significantly higher DAPK2 mRNA expression paralleled by protein induction. In contrast, during differentiation of CD34(+) and U937 cells toward monocytes/macrophages, DAPK2 mRNA levels remained low. In primary leukemia, low expression of DAPK2 was seen in acute myeloid leukemia samples, whereas chronic myeloid leukemia samples in chronic phase showed intermediate expression levels. Lentiviral vector-mediated expression of DAPK2 in NB4 cells enhanced, whereas small interfering RNA-mediated DAPK2 knockdown reduced ATRA-induced granulocytic differentiation, as evidenced by morphology and neutrophil stage-specific maturation genes, such as CD11b, G-CSF receptor, C/EBPepsilon, and lactoferrin. In summary, our findings implicate a role for DAPK2 in granulocyte maturation. PMID- 17347303 TI - Induction of goitrous hypothyroidism by dietary iodide in SJL mice. AB - Prolonged intake of large amounts of iodide has been reported to increase the incidence of goiter and/or hypothyroidism in humans as well as animals prone to spontaneous autoimmune thyroiditis. In the current study, we investigated the role of dietary iodide on the development of hypothyroidism, as well as thyroiditis, in strains of mice that do not develop spontaneous autoimmune thyroiditis. Intake of 0.05% NaI via drinking water for 10 wk induced hypothyroidism in SJL/J mice as indicated by elevated TSH and depressed total T(4) values in serum and formation of colloidal goiter with an inactive flattened thyroid epithelium. Hypothyroidism did not appear to have an autoimmune basis because only focal mononuclear cell infiltrates were found intrathyroidally, and antithyroglobulin antibodies or increased organification of iodide were not detected. These phenomena were not observed in similarly treated CBA/J mice, suggesting polymorphisms in genes controlling events downstream of iodide uptake by thyrocytes. Interestingly, RT-PCR analysis indicated that unlike CBA/J, SJL/J mice could not down-regulate Na/I symporter gene expression during the NaI treatment. No significant temporal or strain differences were observed regarding the expression of thyroglobulin, pendrin, thyroid peroxidase, and DUOX1 and DUOX2 genes after NaI intake. Our results point to the generation of a mouse model for the study of iodine-induced hypothyroidism, which does not seem to have an autoimmune basis. PMID- 17347304 TI - Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. AB - Cancer cachexia is a debilitating syndrome of anorexia and loss of lean body mass that accompanies many malignancies. Ghrelin is an orexigenic hormone with a short half-life that has been shown to improve food intake and weight gain in human and animal subjects with cancer cachexia. We used a rat model of cancer cachexia and administered human ghrelin and a synthetic ghrelin analog BIM-28131 via continuous infusion using sc osmotic minipumps. Tumor-implanted rats receiving human ghrelin or BIM-28131 exhibited a significant increase in food consumption and weight gain vs. saline-treated animals. We used dual-energy x-ray absorptiometry scans to show that the increased weight was due to maintenance of lean mass vs. a loss of lean mass in saline-treated animals. Also, BIM-28131 significantly limited the loss of fat mass normally observed in tumor-implanted rats. We further performed real-time PCR analysis of the hypothalami and brainstems and found that ghrelin-treated animals exhibited a significant increase in expression of orexigenic peptides agouti-related peptide and neuropeptide Y in the hypothalamus and a significant decrease in the expression of IL-1 receptor-I transcript in the hypothalamus and brainstem. We conclude that ghrelin and a synthetic ghrelin receptor agonist improve weight gain and lean body mass retention via effects involving orexigenic neuropeptides and antiinflammatory changes. PMID- 17347305 TI - Peroxisome proliferator-activated receptor alpha protects against obesity-induced hepatic inflammation. AB - Recently it has become evident that obesity is associated with low-grade chronic inflammation. The transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha) has been shown to have a strong antiinflammatory action in liver. However, the role of PPARalpha in obesity-induced inflammation is much less clear. Therefore, the aim of our study was to determine whether PPARalpha plays a role in obesity-induced hepatic inflammation. To induce obesity, wild type sv129 and PPARalpha(-/-) mice were exposed to a chronic high-fat diet (HFD), using a low-fat diet (LFD) as control. In wild-type mice, HFD significantly increased the hepatic and adipose expression of numerous genes involved in inflammation. Importantly, this effect was amplified in PPARalpha(-/-) mice, suggesting an antiinflammatory role of PPARalpha in liver and adipose tissue. Further analysis identified specific chemokines and macrophage markers, including monocyte chemotactic protein 1 and F4/80(+), that were elevated in liver and adipose tissue of PPARalpha(-/-) mice, indicating increased inflammatory cell recruitment in the knockout animals. When all groups of mice were analyzed together, a significant correlation between hepatic triglycerides and expression of inflammatory markers was observed. Many inflammatory genes that were up regulated in PPARalpha(-/-) livers by HFD were down-regulated by treatment with the PPARalpha ligand Wy-14643 under normal nonsteatotic conditions, either in vivo or in vitro, suggesting an antiinflammatory effect of PPARalpha that is independent of reduction in liver triglycerides. In conclusion, our results suggest that PPARalpha protects against obesity-induced chronic inflammation in liver by reducing hepatic steatosis, by direct down-regulation of inflammatory genes, and by attenuating inflammation in adipose tissue. PMID- 17347306 TI - Octreotide and the novel multireceptor ligand somatostatin receptor agonist pasireotide (SOM230) block the adrenalectomy-induced increase in mitotic activity in male rat anterior pituitary. AB - The novel somatostatin receptor agonist pasireotide binds with high affinity to somatostatin receptors SSTR1, 2, 3, and 5. Acting principally through the latter, it inhibits basal and CRH-stimulated ACTH secretion from the AtT20 corticotroph cell line and ACTH release from a proportion of human corticotroph adenomas both in vitro and in vivo. Data supporting an additional antiproliferative effect has led to pasireotide being explored as a potential therapy for patients with Cushing's disease. We have compared the effects of pasireotide and octreotide on adrenalectomy-induced mitotic and apoptotic activity in the male rat anterior pituitary. Adrenalectomized rats were treated with daily sc injections of vehicle, pasireotide, or octreotide. Changes in proliferation and apoptosis were determined 2-6 d postoperatively. Pasireotide and octreotide had no effect on baseline pituitary cell turnover and no measurable effects on apoptosis. However, the wave of increased mitotic activity normally seen in the pituitary after adrenalectomy was completely abolished. Nevertheless, pasireotide and octreotide did not diminish the increase in ACTH-immunopositive cell index after adrenalectomy, indicating that cell division and differentiation of hormonally null cells in the pituitary are under independent control. In conclusion, basal cell turnover in the pituitary is not inhibited by pasireotide or octreotide. Bilateral adrenalectomy stimulates differentiation of preexisting null cells into ACTH-positive cells. Cell division after bilateral adrenalectomy occurs in a specific subpopulation of hormonally null cells that are equally sensitive to the antiproliferative effects of pasireotide and octreotide, implicating SSTR2 receptors in this antimitotic response. PMID- 17347307 TI - Fetal and amniotic insulin-like growth factor-I supplements improve growth rate in intrauterine growth restriction fetal sheep. AB - To date, there is no known prenatal treatment for intrauterine growth restriction (IUGR). IGF-I is an important regulator of fetal growth and circulating IGF-I concentrations are reduced in IUGR fetuses. We investigated whether any of three different methods of fetal IGF-I administration would reverse IUGR in sheep. Animals were randomized into five groups: control (n = 17), IUGR + saline (SAL, n = 17), IUGR + iv IGF-I (IGF-IV, n = 14), IUGR + intraamniotic IGF-I (IGF-AF, n = 14), or IUGR + intraamniotic IGF-I with nutrients (IGF-NUT, n = 16). Weekly IGF-I dose was 360 microg in each treatment group. IUGR was induced by placental embolization between 93 and 99 d and treatment was from 100-128 d gestation (term = 147 d). Embolization caused asymmetrical IUGR with reduced fetal growth rates and body and organ weights, but increased brain to liver weight ratio, at post mortem. Embolized fetuses were also hypoxemic and hypoglycemic and had reduced circulating IGF-I and insulin concentrations. IGF-AF and IGF-IV significantly increased fetal growth rates, but only IGF-AF significantly increased fetal liver weight, compared with saline-treated fetuses. Fetal weights and brain to liver weight ratios in all IGF-I-treated fetuses were intermediate between the control and SAL groups. Addition of nutrients reduced the effects of amniotic IGF-I treatment and increased fetal hemoglobin and lactate concentrations. Treatments did not change fetal plasma IGF-I and insulin concentrations. This is the first report of an intrauterine treatment significantly increasing fetal growth rate in established IUGR. Amniotic IGF-I administration may provide the basis for a clinically applicable prenatal treatment for the IUGR fetus. PMID- 17347308 TI - Alcohol exposure during the developmental period induces beta-endorphin neuronal death and causes alteration in the opioid control of stress axis function. AB - Proopiomelanocortin-producing neurons in the arcuate nucleus of the hypothalamus secrete beta-endorphin (beta-EP), which controls varieties of body functions including the feedback regulation of the CRH neuronal activity in the paraventricular nucleus of the hypothalamus. Whether ethanol exposure in developing rats induces beta-EP neuronal death and alters their influence on CRH neurons in vivo has not been determined. We report here that binge-like ethanol exposures in newborn rats increased the number of apoptotic beta-EP neurons in the arcuate nucleus of the hypothalamus. We also found that immediately after ethanol treatments there was a significant reduction in the expression of proopiomelanocortin and adenylyl cyclases mRNA and an increased expression of several TGF-beta1-linked apoptotic genes in beta-EP neurons isolated by laser captured microdissection from arcuate nuclei of young rats. Several weeks after the ethanol treatment, we detected a reduction in the number of beta-EP neuronal perikarya in arcuate nuclei and in the number of beta-EP neuronal terminals in paraventricular nuclei of the hypothalamus in the treated rats. Additionally, these rats showed increased response of the hypothalamic CRH mRNA to the lipopolysaccharide challenge. The ethanol-treated animals also showed incompetent ability to respond to exogenous beta-EP to alter the lipopolysaccharide-induced CRH mRNA levels. These data suggest that ethanol exposure during the developmental period causes beta-EP neuronal death by cellular mechanisms involving the suppression of cyclic AMP production and activation of TGF-beta1 linked apoptotic signaling and produces long-term structural and functional deficiency of beta-EP neurons in the hypothalamus. PMID- 17347309 TI - Flutamide and cyproterone acetate exert agonist effects: induction of androgen receptor-dependent neuroprotection. AB - Androgens can exert profound effects on the organization, development, and function of the nervous system through activation of androgen receptors (ARs). Nonsteroidal and steroidal antiandrogens antagonize AR-mediated, classic genomic actions of androgens. However, emerging studies in nonneuronal cells indicate that antiandrogens can act as partial agonists for the AR. Here we investigated the effects of the antiandrogens flutamide and cyproterone acetate on neuroprotection induced by dihydrotestosterone (DHT). We observed that, although flutamide and cyproterone acetate blocked androgen-induced gene expression, they failed to inhibit DHT protection against apoptotic insults in cultured hippocampal neurons. Interestingly, flutamide and cyproterone acetate alone, like DHT, significantly reduced apoptosis. Furthermore, the protective actions of flutamide and cyproterone acetate were observed specifically in AR-expressing cell lines, suggesting a role for AR in the agonist effects of antiandrogens. Our results indicate that, in contrast to the classic antiandrogen properties of flutamide and cyproterone acetate, these AR modulators display agonist activities at the level of neuroprotection. These findings provide new insight into the agonist vs. antagonist properties of antiandrogens, information that will be crucial to understanding the neural implications of clinically used AR-modulating drugs. PMID- 17347310 TI - Reversal of defective glucagon responses to hypoglycemia in insulin-dependent autoimmune diabetic BB rats. AB - The intraislet insulin hypothesis has been proposed to explain absent glucagon responses to hypoglycemia. Recently we directly confirmed this hypothesis by restoring glucagon secretion via provision of a pancreatic artery insulin infusion, which was switched off at the time of hypoglycemia in Wistar rats made diabetic by streptozotocin. The current study examined this hypothesis in a model of spontaneous, autoimmune diabetes, the insulin-dependent diabetic BB rat. The insulin switch-off signal restored the defective glucagon responses to hypoglycemia. However, the magnitude of the restored response was markedly less than that observed in control nondiabetic BB rats (4- to 5-month-old diabetic BB rats = 147 +/- 27; 2-month-old nondiabetic BB rats = 1038 +/- 112 pg/ml, peak delta; P < 0.0001). Because time was required for the BB rat to spontaneously develop diabetes, we asked whether the incomplete restoration of the glucagon response might be related to the animals' growth and development. This led us to compare the glucagon response to hypoglycemia in nondiabetic BB and Wistar rats at 2 and 4-5 months of age. We observed age-related deterioration of not only glucose tolerance and insulin sensitivity but also glucagon responses to hypoglycemia in both strains. There was no significant difference between the glucagon responses to hypoglycemia in age-matched nondiabetic BB rats and diabetic BB rats provided with the insulin switch-off signal. We conclude that defective glucagon responses to hypoglycemia in BB rats can be corrected by restoring regulation of alpha-cell function by insulin. PMID- 17347311 TI - Conditional inactivation of the E-cadherin gene in thyroid follicular cells affects gland development but does not impair junction formation. AB - We have conditionally inactivated the E-cadherin gene in the thyroid follicular cells of mouse embryo to unravel its role in thyroid development. We used the Cre loxP system in which the Cre-recombinase was expressed under the control of the tissue-specific thyroglobulin promoter that becomes active at embryonic d 15. At postnatal d 7, thyroid follicle lumens in the knockout mice were about 30% smaller with respect to control mice and had an irregular shape. E-cadherin was almost completely absent in thyrocytes, beta-catenin was significantly reduced, whereas no change in gamma-catenin was detected. alpha-Catenin was also reduced on the cell plasma membrane. Despite the dramatic loss of E-cadherin and beta catenin, cell-cell junctions were not affected, the distribution of tight junction proteins was unaltered, and no increase of thyroglobulin circulating in the blood was observed. In addition, we found that other members of the cadherin family, the R-cadherin and the Ksp-cadherin, were expressed in thyrocytes and that their membrane distribution was not altered in the E-cadherin conditional knockout mouse. Our results indicate that E-cadherin has a role in the development of the thyroid gland and in the expression of beta-catenin, but it is not essential for the maintenance of follicular cell adhesion. PMID- 17347312 TI - Adipocytokines and the regulation of lipid metabolism in growth hormone transgenic and calorie-restricted mice. AB - Chronic elevation of GH induces resistance to insulin and hyperinsulinemia in both humans and animals, whereas calorie restriction (CR) improves peripheral insulin sensitivity in many species. To investigate the mechanisms that lead to insulin resistance in animals with high levels of GH as well as the mechanisms that might improve insulin sensitivity, we fed GH-overexpressing transgenic mice ad libitum or subjected them to 30% CR. We then assayed the plasma adipocytokines levels related to insulin sensitivity, plasma lipid levels, and tissue triglycerides accumulation and examined adipocyte morphology. Furthermore, we evaluated mRNA expression and protein levels of enzymes or regulators involved in regulating hepatic lipid metabolism. Our results suggest that decreased plasma adiponectin, increased plasma resistin and cholesterol, and elevated levels of TNF-alpha and IL-6 in adipocytes may all contribute to the insulin resistance observed in GH-Tg mice. Increased accumulation of triglycerides and impaired adipocytes differentiation in GH-transgenic mice provide plausible mechanisms for the alterations of adipocytokines. Hepatic and muscle insulin resistance in these mice is probably related to excessive accumulation of fatty acids and their metabolites. An increase in plasma adiponectin and decrease in plasma IL-6, triglycerides, and cholesterol levels in response to CR may improve insulin sensitivity. PMID- 17347313 TI - Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice. AB - Apelin, the endogenous ligand of the APJ receptor, has been identified in a variety of tissues, including stomach, heart, skeletal muscle, and white adipose tissue. We sought to clarify the effects of apelin on body adiposity and the expression of uncoupling proteins (UCPs) in C57BL/6 mice. Treatment with ip apelin at a dose of 0.1 mumol/kg.d for 14 d decreased the weight of white adipose tissue and serum levels of insulin and triglycerides, compared with controls, without influencing food intake. Apelin treatment also decreased body adiposity and serum levels of insulin and triglycerides in obese mice fed a high-fat diet. Apelin increased the serum adiponectin level and decreased that of leptin. Additionally, apelin treatment increased mRNA expression of UCP1, a marker of peripheral energy expenditure, in brown adipose tissue (BAT) and of UCP3, a regulator of fatty acid export, in skeletal muscle. In addition, immunoblot bands and relative densities of UCP1 content in BAT were also higher in the apelin group than controls. Furthermore, apelin treatment increased body temperature and O(2) consumption and decreased the respiratory quotient. In conclusion, apelin appears to regulate adiposity and lipid metabolism in both lean and obese mice. In addition, apelin regulates insulin resistance by influencing the circulating adiponectin level, the expression of BAT UCP1, and energy expenditure in mice. PMID- 17347314 TI - Application of MRI of the wrist for age determination in international U-17 soccer competitions. AB - BACKGROUND: To guarantee equal chances for different age groups, age-related tournaments for male and female players have been established in soccer. However, as registration at birth is not compulsory in some countries, other methods of age determination are needed to prevent participation in the incorrect age group. OBJECTIVES: To evaluate the age of soccer players of international U-17 competitions from the degree of fusion of the distal radius and to compare the findings with an age-related normative population. METHODS: MRI scans of the wrist of a representative sample of 189 players from four U-17 competitions (FIFA U-17 World Cups 2003 and 2005, and Asian (AFC) U-17 championships 2004 and 2006) were analysed using a previously published grading system. RESULTS: Because of different regulations, all players in the AFC U-17 championships were younger than 17 years, whereas 71% of the players in the FIFA U-17 World Cup competitions were 17 years old. The distal radius of 15% of players from the AFC U-17 tournaments and 27% of the players from the FIFA U-17 tournaments were graded as completely fused on the MRI scans, which is a substantially higher percentage than in the respective age groups of a previously published normative population of soccer players. Furthermore, in contrast with the normative population, no significant correlation between the age category and the fusion grading (r = 0.13) was observed in U-17 players. CONCLUSION: From the MRI results, U-17 soccer players seem to be more mature than a normative population of the same age category. However, the lack of correlation between age category and degree of fusion in U-17 players supports the suspicion that the age stated in the official documents of the U-17 players examined might not be correct in all cases. PMID- 17347315 TI - Anatomy of the sural nerve in a computer-assisted model: implications for surgical minimal-invasive Achilles tendon repair. AB - BACKGROUND: Sural nerve injuries are an evident risk especially of minimal invasive surgical Achilles tendon repair. However, detailed anatomical studies focusing on the relationship of the sural nerve with the Achilles tendon at various levels are scarce, even pending in two planes. AIM: To determine the position and course of the sural nerve in relation to the Achilles tendon in two planes after trans-section and computer-assisted determination. METHODS: The exact course of the sural nerve was determined in 10 cadavers (55.3 years, 19-89 years), using a computer-assisted method in two planes (transversal/sagittal). RESULTS: The sural nerve crossed the Achilles tendon at 11 (8.7-12.4) cm proximal to the tuber calcanei. The distance between the lateral crossing and the proximal musculotendineus junction was 35 (20-58) mm. Starting from the tuber calcanei, the distance was 2/2 mm (transversal/sagittal plane) at 11 cm proximal to the tuber calcanei, 4/4 mm at 10 cm proximal, 5/6 mm at 9 cm, 8/10 mm at 5 cm and 11/18 mm at the tuber calcanei. CONCLUSION: In the lateral crossing region of the sural nerve and the lateral proximal Achilles tendon 9-12 cm proximal to the tuber calcanei, a close relationship of both anatomical structures can be visualised using computer-assisted measurements; caution is suggested to prevent sural nerve entrapment in either open or percutaneous Achilles tendon repair. PMID- 17347316 TI - Does plyometric training improve vertical jump height? A meta-analytical review. AB - The aim of this study was to determine the precise effect of plyometric training (PT) on vertical jump height in healthy individuals. Meta-analyses of randomised and non-randomised controlled trials that evaluated the effect of PT on four typical vertical jump height tests were carried out: squat jump (SJ); countermovement jump (CMJ); countermovement jump with the arm swing (CMJA); and drop jump (DJ). Studies were identified by computerised and manual searches of the literature. Data on changes in jump height for the plyometric and control groups were extracted and statistically pooled in a meta-analysis, separately for each type of jump. A total of 26 studies yielding 13 data points for SJ, 19 data points for CMJ, 14 data points for CMJA and 7 data points for DJ met the initial inclusion criteria. The pooled estimate of the effect of PT on vertical jump height was 4.7% (95% CI 1.8 to 7.6%), 8.7% (95% CI 7.0 to 10.4%), 7.5% (95% CI 4.2 to 10.8%) and 4.7% (95% CI 0.8 to 8.6%) for the SJ, CMJ, CMJA and DJ, respectively. When expressed in standardised units (ie, effect sizes), the effect of PT on vertical jump height was 0.44 (95% CI 0.15 to 0.72), 0.88 (95% CI 0.64 to 1.11), 0.74 (95% CI 0.47 to 1.02) and 0.62 (95% CI 0.18 to 1.05) for the SJ, CMJ, CMJA and DJ, respectively. PT provides a statistically significant and practically relevant improvement in vertical jump height with the mean effect ranging from 4.7% (SJ and DJ), over 7.5% (CMJA) to 8.7% (CMJ). These results justify the application of PT for the purpose of development of vertical jump performance in healthy individuals. PMID- 17347317 TI - The appropriateness of colonoscopy: a multi-center, international, observational study. AB - OBJECTIVE: To examine the appropriateness and necessity of colonoscopy across Europe. DESIGN: Prospective observational study. SETTING: A total of 21 gastrointestinal centers from 11 countries. PARTICIPANTS: Consecutive patients referred for colonoscopy at each center. INTERVENTION: Appropriateness criteria developed by the European Panel on the Appropriateness of Gastrointestinal Endoscopy, using the RAND appropriateness method, were used to assess the appropriateness of colonoscopy. MAIN OUTCOME MEASURE: Appropriateness of colonoscopy. RESULTS: A total of 5213 of 6004 (86.8%) patients who underwent diagnostic colonoscopy and had an appropriateness rating were included in this study. According to the criteria, 20, 26, 27, or 27% of colonoscopies were judged to be necessary, appropriate, uncertain, or inappropriate, respectively. Older patients and those with a major illness were more likely to have an appropriate or necessary indication for colonoscopy as compared to healthy patients or patients who were 45-54 years old. As compared to screening patients, patients who underwent colonoscopy for iron-deficiency anemia [OR: 30.84, 95% CI: 19.79 48.06] or change in bowel habits [OR: 3.69, 95% CI: 2.74-4.96] were more likely to have an appropriate or necessary indication, whereas patients who underwent colonoscopy for abdominal pain [OR: 0.64, 95% CI: 0.49-0.83] or chronic diarrhea [OR: 0.54, 95% CI: 0.40-0.75] were less likely to have an appropriate or necessary indication. CONCLUSIONS: This study identified significant proportions of inappropriate colonoscopies. Prospective use of the criteria by physicians referring for or performing colonoscopies may improve appropriateness and quality of care, especially in younger patients and in patients with nonspecific symptoms. PMID- 17347318 TI - An exploratory study of cognitive load in diagnosing patient conditions. AB - OBJECTIVE: To determine whether the ways in which information is presented to physicians will improve their ability to respond in a timely and accurate manner to acute care needs. The forms of the presentation compared traditional textual, chart and graph representations with equivalent symbolic language representations. To test this objective, our investigation involved two studies of interpreting patient conditions using two forms of information representation. The first assessed the level of cognitive effort (the outcome variable is known as cognitive load), and the second assessed the time and accuracy outcome variables. PARTICIPANTS: Our investigation consisted of two studies, the first study involved 3rd and 4th year medical students, and the second study involved three board certified physicians who worked in an intensive care unit of a metropolitan hospital. DESIGN: The first study utilized an all-within-subject design with repeated measures, where pretests were utilized as control covariate for prior learning and individual differences. The second study utilized a random sampling of records analyzed by two physicians and qualitatively evaluated by board-certified intensivists. RESULTS: The first study indicated that the cognitive load to interpret the symbolic representation was less than those presented in the more traditional textual, chart and graphic form. The second study suggests that experienced physicians may react in a more timely fashion with at least the same accuracy when the symbolic language was used than with traditional charts and graphs. CONCLUSIONS: The ways in which information is presented to physicians may affect the quality of acute care, such as in intensive, critical and emergency care units. When information can be presented in symbolic form, it may be cognitively processed more efficiently than when it is presented in the usual textual and chart form, potentially lowering errors in diagnosis and increasing the responsiveness to patient conditions. PMID- 17347319 TI - Chromanol 293B binding in KCNQ1 (Kv7.1) channels involves electrostatic interactions with a potassium ion in the selectivity filter. AB - The chromanol 293B (293B, trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3 hydroxy-2,2-dimethyl-chroman) is a lead compound of potential class III antiarrhythmics that inhibit cardiac I(Ks) potassium channels. These channels are formed by the coassembly of KCNQ1 (Kv7.1, KvLQT1) and KCNE1 subunits. Although homomeric KCNQ1 channels are the principal molecular targets, entry of KCNE1 to the channel complex enhances the chromanol block. Because closely related neuronal KCNQ2 potassium channels are insensitive to the drug, we used KCNQ1/KCNQ2 chimeras to identify the binding site of the inhibitor. We localized the putative drug receptor to the H5 selectivity filter and the S6 transmembrane segment. Single residues affecting 293B inhibition were subsequently identified through systematic exchange of amino acids that were either different in KCNQ1 and KCNQ2 or predicted by a docking model of 293B in the open and closed conformation of KCNQ1. Mutant channel proteins T312S, I337V, and F340Y displayed dramatically lowered sensitivity to chromanol block. The predicted drug binding receptor lies in the inner pore vestibule containing the lower part of the selectivity filter, and the S6 transmembrane domain also reported to be important for binding of benzodiazepines. We propose that the block of the ion permeation pathway involves hydrophobic interactions with the S6 transmembrane residues Ile337 and Phe340, and stabilization of chromanol 293B binding through electrostatic interactions of its oxygen atoms with the most internal potassium ion within the selectivity filter. PMID- 17347320 TI - The kinetics of inhibition of human acetylcholinesterase and butyrylcholinesterase by two series of novel carbamates. AB - Controlled inhibition of brain acetyl- and butyrylcholinesterases (AChE and BChE, respectively) and of monoamine oxidase-B (MAO-B) may slow neurodegeneration in Alzheimer's and Parkinson's diseases. It was postulated that certain carbamate esters would inhibit AChE and BChE with the concomitant release in the brain of the OH-derivatives of rasagiline or selegiline that can serve as inhibitors of MAO-B and as antioxidants. We conducted a detailed in vitro kinetic study on two series of novel N-methyl, N-alkyl carbamates and compared them with rivastigmine, a known anti-Alzheimer drug. The rates of carbamylation (k(i)) and decarbamylation (k(r)) of recombinant human AChE were mainly determined by the size of the N-alkyl substituent and to a lesser extent by the nature of the leaving group. k(i) was highest when the alkyl was methyl, hexyl, cyclohexyl, or an aromatic substituent and lowest when it was ethyl. This suggested that k(i) depends on a delicate balance between the length of the residue and its degree of freedom of rotation. By contrast, presumably because of its wider gorge, inhibition of human BChE was less influenced by the size of the alkyl group and more dependent on the structure of the leaving group. The data show how the degree of enzyme inhibition can be manipulated by structural changes in the N methyl, N-alkyl carbamates and the corresponding leaving group to achieve therapeutic levels of brain AChE, BChE, and MAO-B inhibition. PMID- 17347321 TI - Protein kinase A inhibits lysophosphatidic acid-induced migration of airway smooth muscle cells. AB - Lysophosphatidic acid (LPA) is a bioactive phospholipid that is released from activated platelets and affects contractile properties of airway smooth muscle cells. However, possible roles of LPA on cell migration, one of the initial events of airway remodeling, are not clarified. This study aimed to examine the effects of LPA on migration and actin fiber formation in bovine tracheal smooth muscle cells (BTSMCs). Random and oriented cell migrations were examined with wound assay and Boyden chamber assay, respectively. Cytosolic actin fibers were stained with rhodamine-phalloidin. Membrane translocation of RhoA, a hallmark of RhoA activation, was assessed by Western blotting. LPA augmented the migration of BTSMCs from wounded confluent monolayer but did not accelerate the chemotactic migration toward LPA. LPA also induced a transient actin reorganization and RhoA activation. Dense actin fibers were observed mainly in the wound edge but not in migrated cells, thereby suggesting the role of actin reorganization in the initiation of cell migration. LPA-induced actin fiber formation was blocked by Y27632 [R-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane carboxamide], an inhibitor of Rho kinase. Effects of LPA on migration and actin fiber formation were also inhibited by cAMP-elevating agents, i.e., dibutyryl cAMP, forskolin, isoproterenol, and theophylline. KT5720 (9S,10S,12R)-2,3,9,10,11,12-hexahydro-10 hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4 i][1,6]benzodiazocine-10-carboxylic acid hexyl ester], a protein kinase A (PKA) inhibitor, reversed the inhibitory actins of cAMP on LPA-induced responses. These results indicate that LPA induces cAMP/PKA-sensitive, RhoA-mediated random migration of BTSMCs. Regulation of this mechanism would be beneficial for the control of airway remodeling. PMID- 17347322 TI - Rapid modulation of micro-opioid receptor signaling in primary sensory neurons. AB - Management of pain by opioid analgesics is confounded by central adverse effects that limit clinical dosages. Consequently, there is considerable interest to understand peripheral analgesic effects of opioids. The actions of opioids on peripheral sensory neurons have been difficult to study because of a general lack of effect of opioid agonists on nociceptor function in culture despite documented presence of opioid receptors. In this study, the micro-opioid receptor agonist, [D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin (DAMGO), did not alter guanosine 5'-O (3-[(35)S]thio)-triphosphate (GTPgamma[(35)S]) binding, adenylyl cyclase activity, or neuropeptide release in primary cultures of rat trigeminal ganglion (TG). However, after brief exposure to bradykinin (BK), DAMGO stimulated GTPgamma[(35)S] binding and inhibited both prostaglandin E(2) (PGE(2))-stimulated adenylyl cyclase activity and BK/PGE(2)-stimulated neuropeptide release. The effect of BK was blocked by the B(2) antagonist HOE 140 [D-Arg[Hyp(3),Thi(5),D Tic(7),Oic(8)]-bradykinin], but not by the B(1) antagonist, Lys-[Leu8]des-Arg9 BK, and was mimicked by the protease-activated receptor-2 agonist, Ser-Leu-Ile Gly-Arg-Leu-NH(2), and by activation of protein kinase C (PKC) or by administration of arachidonic acid (AA). The enhanced responsiveness of micro opioid receptor signaling by BK priming was blocked by both cyclooxygenase and PKC inhibitors; however, the effect of AA was blocked only by a cyclooxygenase inhibitor. The results indicate that micro-opioid receptor signaling in primary sensory TG neurons is enhanced by activation of phospholipase C-coupled receptors via a cyclooxygenase-dependent AA metabolite that is downstream of PKC. PMID- 17347323 TI - Mutations of Cys-17 and Ala-271 in the human histamine H2 receptor determine the species selectivity of guanidine-type agonists and increase constitutive activity. AB - In a steady-state GTPase activity assay, N-[3-(1H-imidazol-4 yl)propyl)]guanidines and N(G)-acylated derivatives are more potent and efficacious at fusion proteins of guinea pig (gpH(2)R-G(salphaS)) than human (hH(2)R-G(salphaS)) histamine H(2) receptor, coupled to the short splice variant of G(salpha), G(salphaS). Whereas Ala-271 (hH(2)R) and Asp-271 (gpH(2)R) in transmembrane domain 7 were identified to determine the potency differences of guanidine-type agonists, the molecular basis for the efficacy differences remains to be elucidated. A homology model of the gpH(2)R suggested that an H-bond between Tyr-17 and Asp-271 stabilizes an active receptor conformation of the gpH(2)R. In the present study, we generated a mutant hH(2)R-G(salphaS) with Cys 17--> Tyr-17/Ala-271--> Asp-271 exchanges (hH(2)R-->gpH(2)R) that exhibited an enhanced level of constitutive GTPase activity and adenylyl cyclase activity compared with wild-type hH(2)R-G(salphaS) and gpH(2)R-G(salphaS). Potencies and efficacies of guanidines and N(G)-acylguanidines were increased at this mutant receptor compared with hH(2)R-G(salphaS), but they were still lower than at gpH(2)R-G(salphaS), suggesting that aside from Tyr-17 and Asp-271 additional amino acids contribute to the distinct pharmacological profiles of both species isoforms. Another hH(2)R-G(salphaS) mutant with a Cys-17--> Tyr-17 exchange showed inefficient coupling to G(salphaS) as revealed by reduced agonist stimulated GTPase and basal adenylyl cyclase activities. Collectively, our present pharmacological study confirms the existence of an H-bond between Tyr-17 and Asp-271 favoring the stabilization of an active receptor conformation. Distinct potencies and efficacies of agonists and inverse agonists further support the concept of ligand-specific conformations in wild-type and mutant H(2)R-G(salphaS) fusion proteins. PMID- 17347324 TI - S-(1,2,2-trichlorovinyl)-L-cysteine sulfoxide, a reactive metabolite of S-(1,2,2 Trichlorovinyl)-L-cysteine formed in rat liver and kidney microsomes, is a potent nephrotoxicant. AB - Previously, we have provided evidence that cytochromes P450 (P450s) and flavin containing monooxygenases (FMOs) are involved in the oxidation of S-(1,2,2 trichlorovinyl)-L-cysteine (TCVC) in rabbit liver microsomes to yield the reactive metabolite TCVC sulfoxide (TCVCS). Because TCVC is a known nephrotoxic metabolite of tetrachloroethylene, the nephrotoxic potential of TCVCS in rats and TCVCS formation in rat liver and kidney microsomes were investigated. At 5 mM TCVC, rat liver microsomes formed TCVCS at a rate nearly 5 times higher than the rate measured with rat kidney microsomes, whereas at 1 mM TCVC only the liver activity was detectable. TCVCS formation in liver and kidney microsomes was dependent upon the presence of NADPH and was inhibited by the addition of methimazole or 1-benzylimidazole, but not superoxide dismutase, catalase, KCN, or deferoxamine, consistent with the involvement of both FMOs and P450s. Rats given TCVCS at 230 micromol/kg i.p. exhibited acute tubular necrosis at 2 and 24 h after treatment, and they had elevated blood urea nitrogen levels at 24 h, whereas TCVC was a much less potent nephrotoxicant than TCVCS. Furthermore, pretreatment with aminooxyacetic acid enhanced TCVC toxicity. In addition, reduced nonprotein thiol concentrations in the kidney were decreased by nearly 50% 2 h after TCVCS treatment compared with saline-treated rats, whereas the equimolar dose of TCVC had no effect on kidney nonprotein thiol status. No significant lesions or changes in nonprotein thiol status were observed in liver with either TCVC or TCVCS. Collectively, the results suggest that TCVCS may play a role in TCVC-induced nephrotoxicity. PMID- 17347325 TI - Cholesterol potentiates ABCG2 activity in a heterologous expression system: improved in vitro model to study function of human ABCG2. AB - ABCG2, a transporter of the ATP-binding cassette family, is known to play a prominent role in the absorption, distribution, metabolism, and excretion of xenobiotics. Drug-transporter interactions are commonly screened by high throughput systems using transfected insect and/or human cell lines. The determination of ABCG2-ATPase activity is one method to identify ABCG2 substrate and inhibitors. We demonstrate that the ATPase activities of the human ABCG2 transfected Sf9 cell membranes (MXR-Sf9) and ABCG2-overexpressing human cell membranes (MXR-M) differ. Variation due to disparity in the glycosylation level of the protein had no effect on the transporter. The influence of cholesterol on ABCG2-ATPase activity was investigated because the lipid compositions of insect and human cells are largely different from each other. Differences in cholesterol content, shown by cholesterol loading and depletion experiments, conferred the difference in stimulation of basal ABCG2-ATPase of the two cell membranes. Basal ABCG2-ATPase activity could be stimulated by sulfasalazine, prazosin, and topotecan, known substrates of ABCG2 in cholesterol-loaded MXR-Sf9 and MXR-M cell membranes. In contrast, ABCG2-ATPase could not be stimulated in MXR-Sf9 or in cholesterol-depleted MXR-M membranes. Moreover, cholesterol loading significantly improved the drug transport into inside-out membrane vesicles prepared from MXR Sf9 cells. MXR-M and cholesterol-loaded MXR-Sf9 cell membranes displayed similar ABCG2-ATPase activity and vesicular transport. Our study indicates an essential role of membrane cholesterol for the function of ABCG2. PMID- 17347326 TI - Stimulation of Ca2+-gated Cl- currents by the calcium-dependent K+ channel modulators NS1619 [1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5 (trifluoromethyl)-2H-benzimidazol-2-one] and isopimaric acid. AB - Because chloride (Cl(-)) channel blockers such as niflumic acid enhance large conductance Ca(2+)-activated potassium channels (BK(Ca)), the aim of this study was to determine whether there is a reciprocal modification of Ca(2+)-activated chloride Cl(-) currents (I(ClCa)) by two selective activators of BK(Ca). Single smooth muscle cells were isolated by enzymatic digestion from murine portal vein and rabbit pulmonary artery. The BK(Ca) activators NS1619 [1,3-dihydro-1-[2 hydroxy-5-(trifluoromethyl-)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one] and isopimaric acid (IpA) augmented macroscopic I(ClCa) elicited by pipette solutions containing [Ca(2+)](i) > 100 nM without any alteration in current kinetics. Enhanced currents recorded in the presence of NS1619 or IpA reversed at the theoretical Cl(-) equilibrium potential, which was shifted by approximately 40 mV upon replacement of the external anion with the more permeable thiocyanate anion. NS1619 increased the sensitivity of calcium-activated chloride channel (Cl(Ca)) to Ca(2+) (approximately 100 nM at +60 mV) and induced a leftward shift in their voltage dependence (approximately 80 mV with 1 micro Ca(2+)). Single channel experiments revealed that NS1619 increased the number of open channels times the open probability of small-conductance (1.8-3.1 pS) Cl(Ca) without any alteration in their unitary amplitude or number of observable unitary levels of activity. These data, in addition to the established stimulatory effects of niflumic acid on BK(Ca), show that there is similarity in the pharmacology of calcium-activated chloride and potassium channels. Although nonspecific interactions are possible, one alternative hypothesis is that the channel underlying vascular I(ClCa) shares some structural similarity to the BK(Ca) or that the latter K(+) channel physically interacts with Cl(Ca). PMID- 17347327 TI - Significant ocular findings are a feature of heritable bone dysplasias resulting from defects in type II collagen. AB - BACKGROUND/AIMS: The type II collagenopathies are a phenotypically diverse group of genetic skeletal disorders caused by a mutation in the gene coding for type II collagen. Reports published before the causative mutations were discovered suggest heritable bone dysplasias with skeletal malformations may be associated with a vitreoretinopathy. METHODS: A retrospective notes search of patients with a molecularly characterised type II collagenopathy chondrodysplasia who had been examined in the ophthalmology clinic was conducted. RESULTS: 13 of 14 patients had a highly abnormal vitreous appearance. One patient aged 11 presented with a total retinal detachment. Two other children aged 2 and 4 had bilateral flat multiple retinal tears on presentation. 10 of 12 patients refracted were myopic. Two patients had asymptomatic lens opacities: one associated with bilateral inferiorly subluxed lenses and the other with a zonule and lens coloboma. CONCLUSION: Heritable skeletal disorders resulting from a mutation in the gene coding for type II collagen are associated with abnormal vitreous, myopia and peripheral cataract with lens subluxation. In bone dysplasias resulting from a defect of type II collagen there is likely to be a high risk of retinal detachment with a propensity to retinal tears at a young age. PMID- 17347329 TI - A new alcohol provocation head up tilt protocol in the patients with alcohol related syncope. AB - AIMS: Drinking alcohol is known to be one of the triggering factors of neurally mediated syncope. Little is known about the diagnostic utility of the conventional and alcohol provocation head up tilt-test (HUT) in patients with alcohol-related syncope. We investigated the effect of the alcohol provocation HUT. METHODS AND RESULTS: We studied 12 patients (8 males, age 51 +/- 19 years) who had a history of unexplained post-alcohol ingestion syncope. An alcohol provocation protocol HUT (alcohol HUT), in which the protocol required 350 mL of 5% alcohol beer to be drunk over 5 min followed by positioning with the table tilted up for up to 30 min, was performed after the control and isoproterenol (ISP) HUT. None of the subjects (0/12) exhibited a positive response in the control HUT, and only one subject had a positive response (1/12; 8.3%) in the ISP HUT. In the alcohol HUT a positive response (9/12; 75%) increased in the patient group, whereas there were no positive responses in the normal control group. CONCLUSION: In the conventional HUT protocols, including ISP provocation, it was difficult to produce a positive response in the patients with alcohol-related syncope. Alcohol ingestion was a useful diagnostic provocation method in such patients. PMID- 17347328 TI - Presence and phenotype of dendritic cells in uveal melanoma. AB - BACKGROUND: Uveal melanoma arises in an immune-privileged site and can itself add to the immunosuppressive environment. Previous studies on cutaneous melanoma have shown the presence of tolerogenic dendritic cells (DCs), which could play an important role in the progression of the tumour. AIM: To examine the presence and functional status of DCs in a small series of uveal melanomas. METHODS: 10 cases of uveal melanoma were examined for the expression of FXIIIa, CD68, human leucocyte antigen (HLA)-DR, CD40, CD83, transforming growth factor betaR1 and indolamine 2,3 dioxygenase by immunohistochemical analysis on sections embedded in paraffin wax. RESULTS: CD68-positive macrophages were present in all of the tumours and were evenly distributed throughout. DCs expressing FXIIIa-positive were seen in 7 cases, and were often found concentrated in foci within the tumour mass. These cells were dendritic and expressed high levels of HLA-DR. The DCs did not express the maturation markers CD83 or CD40. In one case, concentration of DCs around the area of tumour necrosis was observed, and some of these cells expressed CD83. CONCLUSION: Numerous tolerising antigen-presenting cells may play a role in melanoma-related immunosuppression in the eye, although activation of DCs may be associated with tumour necrosis. PMID- 17347330 TI - Epicardial catheter ablation of ventricular tachycardia using surgical subxyphoid approach. AB - We report the case of a patient presenting with a previous inferior myocardial infarction complicated by incessant monomorphic ventricular tachycardia resistant to antiarrhythmic drugs. Because endocardial catheter ablation failed and because of focal endocardial activation arising from the left ventricular inferior wall, an epicardial location of the reentry circuit was suspected. Catheter mapping of the pericardial space through a surgical subxyphoid approach performed in the electrophysiological laboratory confirmed the epicardial location of the arrhythmogenic substrate and allowed us successfully to ablate and cure the patient. Surgical subxyphoid approach can be performed in the electrophysiological laboratory when epicardial ablation is needed in case of inadvisable, difficult, or failed non-surgical percutaneous access. PMID- 17347331 TI - The letter of Finsterer and Stollberger was shown to the authors who replied. PMID- 17347332 TI - Mechanisms of reinforcement learning and decision making in the primate dorsolateral prefrontal cortex. AB - To a first approximation, decision making is a process of optimization in which the decision maker tries to maximize the desirability of the outcomes resulting from chosen actions. Estimates of desirability are referred to as utilities or value functions, and they must be continually revised through experience according to the discrepancies between the predicted and obtained rewards. Reinforcement learning theory prescribes various algorithms for updating value functions and can parsimoniously account for the results of numerous behavioral, neurophysiological, and imaging studies in humans and other primates. In this article, we first discuss relative merits of various decision-making tasks used in neurophysiological studies of decision making in nonhuman primates. We then focus on how reinforcement learning theory can shed new light on the function of the primate dorsolateral prefrontal cortex. Similar to the findings from other brain areas, such as cingulate cortex and basal ganglia, activity in the dorsolateral prefrontal cortex often signals the value of expected reward and actual outcome. Thus, the dorsolateral prefrontal cortex is likely to be a part of the broader network involved in adaptive decision making. In addition, reward related activity in the dorsolateral prefrontal cortex is influenced by the animal's choices and other contextual information, and therefore may provide a neural substrate by which the animals can flexibly modify their decision-making strategies according to the demands of specific tasks. PMID- 17347333 TI - Safety, antigenicity, and efficacy of a recombinant coccidioidomycosis vaccine in cynomolgus macaques (Macaca fascicularis). AB - The safety, immunogenicity and efficacy of recombinant Ag2/PRA106 + CSA chimeric fusion protein (CFP) vaccine in ISS/Montanide adjuvant-administered intramuscular (IM) was assessed in adult female cynomolgus macaques challenged with Coccidioides posadasii. Animals received three immunizations with either 5 microg CFP, 50-microg CFP, or adjuvant alone and were challenged 4 weeks following the final immunization. Although significant antibody response was produced in response to vaccination, there were no discernable adverse effects, suggesting that the vaccine was well tolerated. Upon intratracheal challenge, all animals showed evidence of disease. Two animals that received 5-microg doses of CFP were euthanatized prior to the study's end because of severe symptoms. Animals vaccinated with 50-microg doses of CFP showed evidence of enhanced sensitization compared to adjuvant controls and animals vaccinated with 5-microg doses of CFP. This was based on higher serum anti-CFP titers, enhanced secretion of interferon gamma (IFN-gamma) from stimulated bronchoalveolar lavage mononuclear cells (BALMC), reduced pulmonary radiologic findings following intratracheal challenge, reduced terminal complement fixation titers, and reduced necropsy findings. Overall the vaccine was well tolerated, induced sensitization, and resulted in a protective response when given at the higher 50-microg dose. Additional experiments may be needed to optimize the vaccination and to confer greater protection against lethal challenge. PMID- 17347334 TI - Structural basis for Ca2+ regulation in the Na+/Ca2+ exchanger. AB - Binding of Na+ and Ca2+ ions to the large cytosolic loop of the Na+/Ca2+ exchanger (NCX) regulates its ion transport across the plasma membrane. We determined the solution structures of two Ca2+-binding domains (CBD1 and CBD2) that, together with an alpha-catenin-like domain (CLD) form the regulatory exchanger loop. CBD1 and CBD2 constitute a novel Ca2+-binding motif and are very similar in the Ca2+-bound state. Strikingly, in the absence of Ca2+ the upper half of CBD1 unfolds while CBD2 maintains its structural integrity. Together with a sevenfold higher affinity for Ca2+ this suggests that CBD1 is the primary Ca2+ sensor. Specific point mutations in either domain largely allow the interchange of their functionality and uncover the mechanism underlying Ca2+ sensing in NCX. PMID- 17347335 TI - A three-dimensional model of the penis for analysis of tissue stresses during normal and abnormal erection. AB - Approximately half of the males between the ages of 40 and 70 suffer erectile dysfunction. Because adequate mechanical interactions in the penis are necessary for functional erection it is important to analyze stresses in the erect penis. Previous penis models were limited to simplified or two-dimensional geometry. Here we developed a three-dimensional model for structural analysis of normal erection as well as erections of a penis with substantial asymmetry of the corporal bodies, and Peyronie's disease. The model was constructed based on anatomical images and included skin, tunica albuginea, corpus cavernosa, and spongiosum. The mechanical behavior of the tunica and skin were assumed to be three-dimensional-orthotropic, and other tissues as well as Peyronie's plaque was taken as linear elastic. Stresses and deformations during erection were analyzed using a commercial finite elements (FE) solver. Erection was simulated by raising blood pressure in the corporal bodies to 100 mmHg. The tunica was found to be the most highly loaded tissue in the erect penis. Peak von Mises stresses in the healthy tunica, tunica of the asymmetric corpora model, and tunica with Peyronie's disease were 114 kPa, 167 kPa, and 830 kPa, respectively. The angles of distortion of the penis with respect to the vertical axis were approximately 4.5 degrees and approximately 2 degrees , for the asymmetric and Peyronie's cases, respectively. The model's ability to determine internal stresses in the erect penis offers a new point of view on the mechanical factors involved with erection, and enables us to relate these data with different penile pathologies. PMID- 17347336 TI - Fluctuations in climate and incidence of coccidioidomycosis in Kern County, California: a review. AB - Coccidioidomycosis (Valley Fever) is a fungal infection found in the southwestern United States, northern Mexico, and some places in Central and South America. The fungi that cause it (Coccidioides immitis and Coccidioides posadasii) are normally soil dwelling, but, if disturbed, become airborne and infect the host when their spores are inhaled. It is thus natural to surmise that weather conditions, which foster the growth and dispersal of Coccidioides, must have an effect on the number of cases in the endemic areas. This article reviews our attempts to date at quantifying this relationship in Kern County, California (where C. immitis is endemic). We have examined the effect on incidence resulting from precipitation, surface temperature, and wind speed. We have performed our studies by means of a simple linear correlation analysis, and by a generalized autoregressive moving average model. Our first analysis suggests that linear correlations between climatic parameters and incidence are weak; our second analysis indicates that incidence can be predicted largely by considering only the previous history of incidence in the county-the inclusion of climate- or weather-related time sequences improves the model only to a relatively minor extent. Our work therefore suggests that incidence fluctuations (about a seasonally varying background value) are related to biological and/or anthropogenic reasons, and not so much to weather or climate anomalies. PMID- 17347337 TI - Implications of resilience concepts for scientific understanding. AB - Resilience is an interactive concept that refers to a relative resistance to environmental risk experiences, or the overcoming of stress or adversity. As such, it differs from both social competence positive mental health. Resilience differs from traditional concepts of risk and protection in its focus on individual variations in response to comparable experiences. Accordingly, the research focus needs to be on those individual differences and the causal processes that they reflect, rather than on resilience as a general quality. Because resilience in relation to childhood adversities may stem from positive adult experiences, a life-span trajectory approach is needed. Also, because of the crucial importance of gene-environment interactions in relation to resilience, a wide range of research strategies spanning psychosocial and biological methods is needed. Five main implications stem from the research to date: (1) resistance to hazards may derive from controlled exposure to risk (rather than its avoidance); (2) resistance may derive from traits or circumstances that are without major effects in the absence of the relevant environmental hazards; (3) resistance may derive from physiological or psychological coping processes rather than external risk or protective factors; (4) delayed recovery may derive from "turning point" experiences in adult life; and (5) resilience may be constrained by biological programming or damaging effects of stress/adversity on neural structures. PMID- 17347338 TI - Competence and resilience in development. AB - The first three waves of research on resilience in development, largely behavioral in focus, contributed a compelling set of concepts and methods, a surprisingly consistent body of findings, provocative issues and controversies, and clues to promising areas for the next wave of resilience research linking biology and neuroscience to behavioral adaptation in development. Behavioral investigators honed the definitions and assessments of risk, adversity, competence, developmental tasks, protective factors, and other key aspects of resilience, as they sought to understand how some children overcome adversity to do well in life. Their findings implicate fundamental adaptive systems, which in turn suggest hot spots for the rising fourth wave of integrative research on resilience in children, focused on processes studied at multiple levels of analysis and across species. PMID- 17347339 TI - Contributions of temperament to buffering and sensitization processes in children's development. AB - Temperament refers to relatively stable, early appearing, biologically rooted individual differences in behavioral traits. Individual differences in temperament are multidetermined encompassing both biological and experiential influences. Evidence indicates that certain temperament traits, such as impulsivity, inhibition, and negative emotionality, can serve as developmental risk factors. Evidence also indicates that other temperament traits, such as flexible self-regulation, sociability, and task orientation, can serve to increase children's resilience. Five potential mechanisms through which individual differences in temperament can increase vulnerability or facilitate resilience are presented: (1) Differential treatment of children with different temperaments by caregivers or teachers (reactive covariance). (2) Children with different temperament styles seeking out environments that may increase risk or promote resilience (active covariance). (3) Goodness or poorness of fit between child temperament characteristics and environmental demands. (4) Children with different temperaments reacting to similar levels or types of stress in different ways. (5) Different coping strategies used by children with different temperaments. PMID- 17347340 TI - Resilience as an attribute of the developmental system: comments on the papers of Professors Masten & Wachs. AB - When conceptualized within a developmental systems theoretical framework, resilience involves mutually beneficial, reciprocally influential relations between a person and his or her context. The key features of developmental systems theory, which stress the plasticity of these relations, lead to an optimistic view of the possibility of promoting positive human development (PHD) across the life span. The results of recent longitudinal research about adolescent development allow this period to serve as a sample case of how positive development is associated with the alignment of the strengths of individuals with ecological resources for healthy growth. PMID- 17347341 TI - Risk, resilience, and gene x environment interactions in rhesus monkeys. AB - Recent research with both humans and rhesus monkeys has provided compelling evidence of gene-environment (GxE) interactions throughout development. For example, a specific polymorphism ("short" allele) in the promoter region of the serotonin transporter (5-HTT) gene is associated with deficits in neurobehavioral functioning during infancy and in poor control of aggression and low serotonin metabolism throughout juvenile and adolescent development in monkeys who were reared with peers but not in monkeys who were reared with their mothers and peers during infancy. In contrast, monkeys possessing the "long" allele of the 5-HTT gene exhibit normal neurobehavioral functioning, control of aggression, and serotonin metabolism regardless of their early social rearing history. One interpretation of these GxE interaction data is that the "long" 5-HTT allele somehow confers resiliency to adverse early attachment relationships on those individuals who carry it ("good genes"). An alternative interpretation of the same data is that secure attachment relationships somehow confer resiliency to individuals who carry alleles that may otherwise increase their risk for adverse developmental outcomes ("maternal buffering"). These two interpretations are not mutually exclusive, but the difference in their respective implications for developing prevention and even intervention strategies is considerable. Moreover, the allelic variation seen in certain genes in rhesus monkeys and humans but apparently not in other primate species may actually contribute to their remarkable adaptability and resilience at the species level. PMID- 17347342 TI - Cumulative, human capital, and psychological risk in the context of early intervention: links with IQ at ages 3, 5, and 8. AB - This article examines the effects of risks for a sample of low birth weight children (2,001 to 2,500 g and family income-to-needs at 250% of the poverty threshold or less; n = 228) using data from the Infant Health and Development Program (IHDP, an experiment testing the efficacy of early intervention). Cognitive test scores (IQ) are assessed at 3, 5, and 8 years of age. Links with risks at each age point are examined using three different models-cumulative, human capital, and psychological risks. Similar decrements in IQ scores are found at all ages for the cumulative and human capital models but not for the psychological risk model. Treatment effects are found at 3 years of age (when the intervention ended) for all levels of risk and for all models. Sustained effects of the treatment were found at 5 and 8 years of age for children with moderate levels of human capital risk but were not found for any levels of psychological risk. Implications for early childhood intervention programs are discussed. PMID- 17347343 TI - The inherent stress of normal daily life and social interaction leads to the development of coping and resilience, and variation in resilience in infants and young children: comments on the papers of Suomi and Klebanov & Brooks-Gunn. AB - The hypothesis is advanced that behavioral and physiologic resilience develops in part from infants' and young children's experience coping with the inherent normal stress of daily life and social interaction. Data on the stress of normal social interactions and perturbated interactions from the Face-to-Face Still-Face Paradigm (FFSF) are presented for young infants. These findings, including behavioral, heart rate and vagal tone, and electrodermal reactivity demonstrate the stress inherent in normal interaction and how coping with normal stress develops infants' coping with more intense environmental and social stressors. PMID- 17347344 TI - Conceptual issues in studies of resilience: past, present, and future research. AB - We begin this article by considering the following critical conceptual issues in research on resilience: (1) distinctions between protective, promotive, and vulnerability factors; (2) the need to unpack underlying processes; (3) the benefits of within-group experimental designs; and (4) the advantages and potential pitfalls of an overwhelming scientific focus on biological and genetic factors (to the relative exclusion of familial and contextual ones). The next section of the article is focused on guidelines for the selection of vulnerability and protective processes in future research. From a basic science standpoint, it is useful and appropriate to investigate all types of processes that might significantly affect adjustment among at-risk individuals. If the research is fundamentally applied in nature, however, it would be most expedient to focus on risk modifiers that have high potential to alter individuals' overall life circumstances. The final section of this article considers conceptual differences between contemporary resilience research on children versus adults. Issues include differences in the types and breadth of outcomes (e.g., the tendencies to focus on others' ratings of competence among children and on self reports of well-being among adults respectively). PMID- 17347345 TI - Psychosocial constraints on the development of resilience. AB - Although resilience is usually thought to reside in individuals, developmental research is increasingly demonstrating that characteristics of the social context may be better predictors of resilience. When the relative contribution of early resilience and environmental challenges to later child mental health and academic achievement were compared in a longitudinal study from birth to adolescence, indicators of child resilience, such as the behavioral and emotional self regulation characteristic of good mental health, and the cognitive self regulation characteristic of high intelligence contributed to later competence. However, the effects of such individual resilience did not overcome the effects of high environmental challenge, such as poor parenting, antisocial peers, low resource communities, and economic hardship. The effects of single environmental challenges become very large when accumulated into multiple risk scores even affecting the development of offspring in the next generation. PMID- 17347346 TI - Adolescents' resilience as a self-regulatory process: promising themes for linking intervention with developmental science. AB - This chapter focuses on the concept of self-regulation as a measure of resilience in children and adolescents. Developmental psychology and neuroscience are converging on the role of attention control as a central ability underlying self regulation. We collected measures of adolescent attention control from parents and youth, and a measure of self-regulation from teachers. The measures of effortful attention correlated highly with teacher ratings of self-regulation. The composite measure of self-regulation (youth, parent, teacher report) was found to moderate the impact of peer deviance on adolescent antisocial behavior, as well as stress on adolescent depression. These findings suggest that self regulation is a promising index of adolescent resilience. The construct of self regulation also provides an excellent target for strategies aimed to improve child and adolescent adjustment in problematic environments and stressful circumstances. PMID- 17347347 TI - Promoting resilience in children and youth: preventive interventions and their interface with neuroscience. AB - Preventive interventions focus on reducing risk and promoting protective factors in the child as well as their cultural ecologies (family, classroom, school, peer groups, neighborhood, etc). By improving competencies in both the child and their contexts many of these interventions promote resilience. Although there are now a substantial number of preventive interventions that reduce problem behaviors and build competencies across childhood and adolescence, there has been little integration with recent findings in neuropsychology and neuroscience. This article focuses on the integration of prevention research and neuroscience in the context of interventions that promote resilience by improving the executive functions (EF); inhibitory control, planning, and problem solving skills, emotional regulation, and attentional capacities of children and youth. Illustrations are drawn from recent randomized controlled trials of the Promoting Alternative Thinking Strategies (PATHS) curriculum. The discussion focuses on the next steps in transdisciplinary research in prevention and social neuroscience. PMID- 17347348 TI - Prevention approaches to enhance resilience among high-risk youth: comments on the papers of Dishion & Connell and Greenberg. AB - This article synthesizes research on resilience theory and its implications for prevention interventions to increase resilience in high-risk children and adolescents. In addition, this response to both the articles by Drs. Greenberg and Dishion summarizes their key points. Their papers discuss the neuroscience substrate behind two major mediators of antisocial behaviors, namely lack of self regulation and executive function problems. In addition, we present an overall Resilience Framework that will help the reader organize the aspects of resilience discussed by these two researchers into a transactional process model. This article extends prior researchers' suggestion that resilience is the product of the interaction of genetic, biological, and environmental precursors to a further consideration of higher-level cognitive precursors, such as purpose in life and existential meaning. The relevance of resilience to the prevention of negative outcomes in high-risk children of alcoholics (COAs) and substance abusers is covered. Within this third wave of resilience research on prevention interventions, we present data suggesting that family strengthening approaches have the greatest impact on increasing resilience. PMID- 17347349 TI - Behavioral differences in aggressive children linked with neural mechanisms of emotion regulation. AB - Children with aggressive behavior problems may have difficulties regulating negative emotions, resulting in harmful patterns of interpersonal behavior at home and in the schoolyard. Ventral and dorsal regions of the prefrontal cortex (PFC) have been associated with response inhibition and self-control-key components of emotion regulation. Our research program aims to explore differences among aggressive and normal children in the activation of these cortical regions during emotional episodes, to the extent possible using electrophysiological techniques, to identify diagnostic subtypes, gain insights into their interpersonal difficulties, and help develop effective treatment strategies. This report reviews several recent studies investigating individual and developmental differences in cortical mechanisms of emotion regulation, corresponding with different patterns of interpersonal behavior. Our methods include event-related potentials (ERPs) and cortical source modeling, using dense array electroencephalography (EEG) technology, as well as videotaped observations of parent-child interactions, with both normal and aggressive children. By relating patterns of brain activation to observed behavioral differences, we find (i) a steady decrease in cortical activation subserving self-regulation across childhood and adolescence, (ii) different cortical activation patterns as well as behavioral constellations distinguishing subtypes of aggressive children, and (iii) robust correlations between the activation of cortical mediators of emotion regulation and flexibility in parent-child emotional communication in children referred for aggressive behavior problems. These findings point toward models of developmental psychopathology based on the interplay among biological, psychological, and social factors. PMID- 17347350 TI - Arousal regulation, emotional flexibility, medial amygdala function, and the impact of early experience: comments on the paper of Lewis et al. AB - The balance between optimal levels of emotional arousal and cognitive performance reflects the integration of several dopaminergically and adrenergically regulated neural systems. The amygdalar system is a key region for gating stimulation to cortical regions and the medial amygdala appears to play an especially key role in mediating the fear response. More generally, these arousal regulatory neural systems are key to frustration or stress impact prefrontal cortical function. Further, the threshold for when the level of stress is overwhelming and hence impairs cognitive function reflects minimally genetic and experiential influence. An important interface between Drs. Lewis and Davis's work is how early experience, especially through early parenting, may set the threshold of responsiveness for these arousal regulatory neural systems. PMID- 17347351 TI - Genetic and environmental influences on the development of alcoholism: resilience vs. risk. AB - The physiological changes of adolescence may promote risk-taking behaviors, including binge drinking. Approximately 40% of alcoholics were already drinking heavily in late adolescence. Most cases of alcoholism are established by the age of 30 years with the peak prevalence at 18-23 years of age. Therefore the key time frame for the development, and prevention, of alcoholism lies in adolescence and young adulthood. Severe childhood stressors have been associated with increased vulnerability to addiction, however, not all stress-exposed children go on to develop alcoholism. Origins of resilience can be both genetic (variation in alcohol-metabolizing genes, increased susceptibility to alcohol's sedative effects) and environmental (lack of alcohol availability, positive peer and parental support). Genetic vulnerability is likely to be conferred by multiple genes of small to modest effects, possibly only apparent in gene-environment interactions. For example, it has been shown that childhood maltreatment interacts with a monoamine oxidase A (MAOA) gene variant to predict antisocial behavior that is often associated with alcoholism, and an interaction between early life stress and a serotonin transporter promoter variant predicts alcohol abuse in nonhuman primates and depression in humans. In addition, a common Met158 variant in the catechol-O-methyltransferase (COMT) gene can confer both risk and resilience to alcoholism in different drinking environments. It is likely that a complex mix of gene(s)-environment(s) interactions underlie addiction vulnerability and development. Risk-resilience factors can best be determined in longitudinal studies, preferably starting during pregnancy. This kind of research is important for planning future measures to prevent harmful drinking in adolescence. PMID- 17347352 TI - Stress and the adolescent brain. AB - During adolescence the brain shows remarkable changes in both structure and function. The plasticity exhibited by the brain during this pubertal period may make individuals more vulnerable to perturbations, such as stress. Although much is known about how exposure to stress and stress hormones during perinatal development and adulthood affect the structure and function of the brain, relatively little is known about how the pubertal brain responds to stress. Furthermore, it is not clear whether stressors experienced during adolescence lead to altered physiological and behavioral potentials in adulthood, as has been shown for perinatal development. The purpose of this review is to present what is currently known about the pubertal maturation of the hypothalamic-pituitary adrenal (HPA) axis, the neuroendocrine axis that mediates the stress response, and discuss what is currently known about how stressors affect the adolescent brain. Our dearth of knowledge regarding the effects of stress on the pubertal brain will be discussed in the context of our accumulating knowledge regarding stress-induced neuronal remodeling in the adult. Finally, as the adolescent brain is capable of such profound plasticity during this developmental stage, we will also explore the possibility of adolescence as a period of interventions and opportunities to mitigate negative consequences from earlier developmental insults. PMID- 17347353 TI - Effects of therapeutic interventions for foster children on behavioral problems, caregiver attachment, and stress regulatory neural systems. AB - Young children in foster care are exposed to high levels of stress. These experiences place foster children at risk for poor social, academic, and mental heath outcomes. The role of adverse events in stimulating neurobiological stress responses presumably plays a role in shaping neural systems that contribute to these problems. Systematic and developmentally well-timed interventions might have the potential to change developmental trajectories and promote resilience. Moreover, understanding how specific dimensions of early adversity affect underlying stress response systems and how alterations in these systems are related to later psychosocial outcomes might facilitate more precise and targeted interventions. Data are drawn from two ongoing randomized trials involving foster infants/toddlers and preschoolers. Consistent with prior animal models of early adversity, these studies have shown that early adversity-particularly neglect, younger age at first foster placement, and higher number of placements-is associated with altered hypothalamic-pituitary-adrenal (HPA) axis function. The interventions under investigation have produced evidence that it is possible to impact many areas that have been negatively affected by early stress, including HPA axis activity, behavior, and attachment to caregivers. PMID- 17347354 TI - Psychobiological processes of stress and coping: implications for resilience in children and adolescents--comments on the papers of Romeo & McEwen and Fisher et al. AB - The significance of psychosocial stress and ways of coping with stress for understanding resilience in childhood and adolescence are reviewed. Psychological and biological processes of reactivity to and recovery from stress are central in understanding the physical and emotional tolls that result from prolonged exposure to chronic stress. A central theme of this article is that stress exerts a double toll on physical and emotional health and well-being. First, as a consequence of allostatic load, stress contributes to disease and disorder. And second, because of effects on specific brain regions, chronic stress takes a second toll by disrupting function in those regions primarily responsible for coping and self-regulation. Implications for future research on resilience and the development of interventions to promote resilience are highlighted. PMID- 17347355 TI - Prevention of pediatric bipolar disorder: integration of neurobiological and psychosocial processes. AB - Bipolar disorder (BD) is a prevalent condition in the United States that typically begins before the age of 18 years and is being increasingly recognized in children and adolescents. Despite great efforts in discovering more effective treatments for BD, it remains a difficult-to-treat condition with high morbidity and mortality. Therefore, it appears prudent to focus energies into developing interventions designed to prevent individuals from ever fully developing BD. Such interventions early in the development of the illness might prevent inappropriate interventions that may worsen or hasten development of BD, delay the onset of first manic episode, and/or prevent development of full BD. Studies of populations at high-risk for BD development have indicated that children with strong family histories of BD, who are themselves experiencing symptoms of attention-deficit/hyperactive disorder (ADHD) and/or depression or have early mood dysregulation, may be experiencing prodromal states of BD. Understanding the neurobiological and genetic underpinnings that create risk for BD development would help with more accurate identification of this prodromal population, which could then lead to suitable preventative interventions. Such interventions could be pharmacologic or psychosocial in nature. Reductions in stress and increases in coping abilities through psychosocial interventions could decrease the chance of a future manic episode. Similarly, psychotropic medications may decrease negative sequelae of stress and have potential for neuroprotective and neurogenic effects that may contribute to prevention of fully expressed BD. Further research into the biologic and environmental mechanisms of BD development as well as controlled early intervention studies are needed to ameliorate this significant public health problem. PMID- 17347356 TI - A multiple-levels-of-analysis perspective on resilience: implications for the developing brain, neural plasticity, and preventive interventions. AB - Resilient functioning, the attainment of unexpected competence despite significant adversity, is among the most intriguing and adaptive phenomena of human development. Although growing attention has been paid to discovering the processes through which individuals at high risk do not develop maladaptively, the empirical study of resilience has focused predominantly on detecting the psychosocial determinants of the phenomenon. For the field of resilience to grow in ways that are commensurate with the complexity inherent to the construct, efforts to understand underlying processes will be facilitated by the increased implementation of interdisciplinary research designed within a developmental psychopathology framework. Research of this nature would entail a consideration of psychological, biological, and environmental-contextual processes from which pathways to resilience might eventuate (known as equifinality), as well as those that result in diverse outcomes among individuals who have achieved resilient functioning (know as multifinality). The possible relation between the mechanisms of neural plasticity and resilience and specific suggestions concerning research questions needed to examine this association are discussed. Examples from developmental neuroscience and molecular genetics are provided to illustrate the potential of incorporating biology into the study of resilience. The importance of adopting a multiple-levels-of-analysis perspective for designing and evaluating interventions aimed at fostering resilient outcomes in persons facing significant adversity is emphasized. PMID- 17347357 TI - Evolutionary basis of adaptation in resilience and vulnerability: response to Cicchetti and Blender. AB - This masterful and wide-ranging paper gives us a clear picture of the need for interdisciplinary studies of resilience and vulnerability. We need to go beyond the interacting events at the different levels to see clearly that multiple levels of analysis and concept do not themselves interact, but instead give us different aspects of a biological, psychological, or behavioral event. Thus, no levels are reducible to any of the others. In the rest of my discussion, I raise the likelihood that the multiple level responses of "resilience" are no more adaptive in their evolutionary history than the very different responses we call "vulnerability." Keeping in mind the evolved functions of these responses, and the circumstances of their selection during evolution, will provide us with new ideas and approaches for understanding and intervention. PMID- 17347358 TI - Maternal sensitivity is related to hypothalamic-pituitary-adrenal axis stress reactivity and regulation in response to emotion challenge in 6-month-old infants. AB - This study examined relations between maternal sensitivity as observed in a free play interaction and changes in levels of the glucocorticoid hormone cortisol in response to procedures designed to elicit negative affect in 6-month old infants. The sample included 1,292 families in predominantly rural and low-income communities in Pennsylvania and North Carolina. Results indicated that infants of more sensitive mothers had lower levels of cortisol at baseline and increased cortisol reactivity and regulation in response to the emotion procedures. Maternal negativity was unrelated to infant cortisol. Findings highlight the need for further research on variation in early caregiving and the development of the stress response in young children. PMID- 17347359 TI - Ultrasound consultation to reduce risk and increase resilience in pregnancy. AB - Clinical evidence indicates the influence of viewing ultrasound on women's investment in health during pregnancy. Ongoing work on the effects of ultrasound consultation (UC) include: establishing a replicable UC and demonstrating validity of the UC by examining effects of UC on behavioral and physiological indicators of increased resilience in maternal health and pregnancy outcome. The study indicated that UC significantly increased maternal-fetal attachment, decreased maternal anxiety, and increased positive attitudes toward health during pregnancy. Ongoing research involves using UC in two protocols with pregnant women, for instance, those experiencing moderate-to-severe depression and those at risk for noncompliance in treatment for gestational diabetes. PMID- 17347360 TI - Emotional resilience in early childhood: developmental antecedents and relations to behavior problems. AB - To test whether the development of emotional resilience is a function of sensitive caregiving and child negative affect, we tested the joint contributions of 7-month maternal sensitivity and infant negative affect to the prediction of 33-month emotional resilience across the first 3 years of life. The aims of this study were to examine whether maternal sensitivity and infant negative affect predict long-term emotional resilience and whether this was associated with preschool behavior problems. Using a sample of 181 mother-infant dyads, we found that (a) maternal sensitivity at 7 months, but not infant negative affect, longitudinally predicted emotional resilience during preschool and (b) emotional resilience was negatively associated with anxiety/depression in preschool. PMID- 17347361 TI - The role of verbal competence and multiple risk on the internalizing behavior problems of Costa Rican youth. AB - This longitudinal study examined internalizing behavior problems (anxiety/depression) in early adolescence in relation to adversity in early childhood and child verbal competence. We hypothesized that verbal competence would act as a protective factor in the face of early adversity, that is, high verbal IQ would predict relatively lower internalizing problems in early adolescence primarily for those children who experienced the greatest adversity. The sample was based on 191 Costa Rican children and their mothers, who were recruited in infancy from an urban community and assessed again at 5 and 11-14 years. Families were generally lower-middle to working class. A total of 165 children (94 boys) participated in the early adolescent follow-up (mean age = 12.3 years). Internalizing problems were based on maternal report (Spanish Child Behavior Checklist). Our cumulative risk index (CRI)_of adversity in early childhood consisted of home environment quality (HOME score), socioeconomic status, maternal depressed mood (CESD), and maternal IQ. Controlling for the effects of age, gender, internalizing problems at 5 years, and verbal IQ at 5 years, there was a significant interaction between early adversity and verbal IQ at age 11-14 years in predicting internalizing problems in early adolescence. Youth with high verbal IQ had comparable levels of internalizing problems regardless of high or low adversity in early childhood. In contrast, youth with low verbal IQ received higher internalizing problem ratings if they experienced high adversity early in life. The results raise the possibility that interventions to improve verbal competence might help lower the risk of internalizing problems in the face of early adversity. PMID- 17347362 TI - Preventing co-occurring depression symptoms in adolescents with conduct problems: the Penn Resiliency Program. AB - Children who exhibit elevated levels of conduct problems are at increased risk for developing co-occurring depression symptoms, especially during adolescence. This study tests the effectiveness of a manualized after school intervention (the Penn Resiliency Program [PRP]) for the prevention of depression symptoms among a subset of middle-school-aged students who exhibited elevated levels of conduct problems, but not depression symptoms, at the start of the study. Longitudinal analyses demonstrate that the program successfully prevented elevations in depression symptoms across early- to mid-adolescence compared to no-intervention controls. PMID- 17347363 TI - Maternal depression and psychotropic medication effects on the human fetus. AB - Ultrasound studies examined fetuses of depressed and nondepressed mothers. Fetuses of depressed mothers were more active during mid-gestation and exhibited lower baseline heart rate and moved less during late-term vibratory stimulation. Mid-gestation heightened activity and late-term diminished responsivity may be a prenatal manifestation of the "general adaptation syndrome." Color Doppler technology measured blood flow velocity in the middle cerebral artery of fetuses whose mothers were prescribed SSRIs or lithium. SSRIs were associated with velocity increases and lithium with velocity decreases. The effects of psychotropic medications on prenatal neurobehavioral development require further study to document potential benefits and adverse effects. PMID- 17347364 TI - More than maternal sensitivity shapes attachment: infant coping and temperament. AB - The aim of this longitudinal study was to investigate the effect of a set of factors from multiple levels of influence: infant temperament, infant regulatory behavior, and maternal sensitivity on infant's attachment. Our sample consisted of 48 infants born prematurely and their mothers. At 1 and 3 months of age, mothers described their infants' behavior using the Escala de Temperamento do Bebe. At 3 months of age, infants' capacity to regulate stress was evaluated during Tronick's Face-to-Face Still-Face (FFSF) paradigm. At 9 months of age, mothers' sensitivity was evaluated during free play using the CARE-Index. At 12 months of age, infants' attachment security was assessed during Ainsworth's Strange Situation. A total of 16 infants were classified as securely attached, 17 as insecure-avoidant, and 15 as insecure-resistant. Mothers of securely attached infants were more likely than mothers of insecure infants to describe their infants as less difficult and to be more sensitive to their infants in free play. In turn, secure infants exhibited more positive responses during the Still-Face. Infants classified as insecure-avoidant were more likely to self-comfort during the Still-Face and had mothers who were more controlling during free play. Insecure-resistant exhibited higher levels of negative arousal during the Still Face and had mothers who were more unresponsive in free play. These findings show that attachment quality is influenced by multiple factors, including infant temperament, coping behavior, and maternal sensitivity. PMID- 17347365 TI - Infant resilience to the stress of the still-face: infant and maternal psychophysiology are related. AB - Respiratory sinus arrhythmia (RSA) is related to infant emotion regulation and resilience. However, few studies have examined RSA of infants and mothers during a stressful experience. Even fewer studies have measured infant and mother skin conductance (SC), which in part reflects anxiety. This pilot study examined RSA, heart rate (HR), and SC patterns of 12 five-month-old infants and their mothers during normal interaction and a stressful perturbation of the interaction in which the mother does not respond to her infant-the Face-to-Face Still-Face (FFSF) paradigm. Dyads were grouped into four categories by two conditions: whether the infant protested to the Still-Face episode (SF) and whether they "recovered" from the SF by reducing protest when the mother resumed interaction in the Reunion (RE). Infants who recovered from the SF had the largest increase in RSA from SF to RE. Mothers of infants who recovered from the SF showed a decrease in RSA during the RE, suggesting mobilization of infant soothing behaviors. Mothers of infants who did not recover from the SF showed physiologic markers of anxiety in the form of continued increases in RSA and high levels of SC. Furthermore, these mothers behaved in a manner that was not responsive to their infant's disengagement cues. These pilot results demonstrate the feasibility of measuring infant SC, a measure long disregarded in infant research. The findings suggest that maternal psychophysiology may be related to infant resilience and suggest a bidirectional effect of maternal and infant reactivity. PMID- 17347366 TI - Children survivors of the 2004 tsunami in Aceh, Indonesia: a study of resiliency. AB - This exploratory study investigates factors contributing to resiliency of children in the age group of 11-15 years, survivors of the 2004 tsunami in Aceh, Indonesia, through qualitative methodology. Series of participative observation and interviews with children, parents, and local social workers were conducted. A group of 50 children from three camps of the tsunami-affected areas in Banda Aceh and Great Aceh were involved and observed through several psychosocial activities conducted in coordination with local social workers in the community. Resilient children were identified based on criteria that were developed from the context of the tsunami-affected children in Banda Aceh and Great Aceh. Six children were identified as resilient. They show absence of clinically significant levels of trauma-related symptoms as measured by Trauma Symptom Checklist for Children-A (TSCC-A). They are able to live normally, such as participate in school activities, play with friends, perform daily chores, be involved in religious activities, and develop healthy relationships with caregivers and peers. They are also perceived as cooperative in psychosocial activities. Findings in internal protective factors of these children include: strong internal motivation to recover, good heart, open to other people, high motivation to bond to religiosity, self-responsible, sense of humor, and easygoing. Contributing external factors include: support from significant others, able to do religious practice routinely, able to learn traditional dance in groups, have opportunities to be involved in structured play/psychosocial activities, and have access to natural resources for recreation, such as a river. PMID- 17347367 TI - Frontal EEG asymmetry and regulation during childhood. AB - Previous research suggests an association between frontal electroencephalographic (EEG) asymmetries and both positive and negative emotion reactivity. Specifically, right frontal EEG activation is associated with emotions of negative valence in both infants and adults, whereas left frontal EEG activation is associated with emotions of more positive valence. Relatively few studies have examined such associations in children. Moreover, research on mechanisms through which emotion reactivity is related to frontal EEG asymmetries is sparse. As one possible mechanism, we hypothesize that regulatory skills and behaviors developing rapidly during childhood play a critical role in linking frontal EEG asymmetries to emotion reactivity in children. To test the research hypothesis, 25 children were followed from early-to-middle childhood at two different points in time with a 4-year interview interval. Results show that individual variations in a number of regulatory behaviors among children are significantly associated with frontal EEG asymmetries. Our results provide support for the possibility of frontal EEG asymmetry informing the study of the development of regulation in children. The discussion of the findings is centered on potential risk for and resilience to children's emotional reactivity and regulation. PMID- 17347368 TI - Violence and delinquency, early onset drug use, and psychopathology in drug exposed youth at 11 years. AB - In this first study of violence and resilience in 517 youth exposed to cocaine and other drugs during pregnancy, we identified specific links between four types of violence and delinquency, drug use, and psychopathology in early adolescence. Further, positive and interpersonal attributes promoted resilience in the face of exposure to violence and other risks. This study provides new evidence for the impact of violence as well as resilience against disruptive forms of psychopathology and behavior. PMID- 17347369 TI - Explorations of coping strategies, learned persistence, and resilience in Long Evans rats: innate versus acquired characteristics. AB - In the current investigation, predispositions for coping styles (i.e., passive, flexible, and active) were determined in juvenile male rats. In subsequent behavioral tests, flexible copers exhibited more active responses. In another study, animals were exposed to chronic stress and flexible coping rats had lower levels of corticosteroids. Focusing on the acquired nature of coping strategies, rats receiving extensive training in a task requiring them to dig for food rewards (i.e., effort-based rewards) persisted longer in a challenging task than control animals. Thus, the results suggest that both predisposed coping strategies and acquired behavioral experience contribute to resilience in challenging situations. PMID- 17347370 TI - Biobehavioral indices of emotion regulation relate to school attitudes, motivation, and behavior problems in a low-income preschool sample. AB - Effective emotion regulation may promote resilience and preschool classroom adjustment by supporting adaptive peer interactions and engagement in learning activities. We investigated how hypothalamus-pituitary-adrenal axis (HPA) regulation, cardiac reactivity, and classroom emotion displays related to adjustment among low-income preschoolers attending Head Start. A total of 62 four year-olds completed a laboratory session including a baseline soothing video; emotion-eliciting slides/video clips, and recovery. Salivary cortisol, heart rate, and vagal tone were measured throughout. Independent coders used handheld computers to observe classroom emotion expression/regulation. Teachers rated child motivation, persistence/attention, learning attitudes, and internalizing/externalizing symptoms. Results reveal associations between biobehavioral markers of regulatory capacity and early school adjustment. PMID- 17347371 TI - Additive interaction of child abuse and perinatal risk as signs of resiliency in adulthood. AB - To find the biological basis of resilience, we exploited data from a longitudinal community-based study of 1,748 adult children, followed from birth to adulthood. Results showed that those with both abuse and perinatal problems demonstrated synergistically impaired well-being, a higher rate of school dropout, lower sense of success, and lower income. Among abused adult children (n = 271), we found that those without, relative to those with, perinatal problems had lower risk for adult psychopathology. An examination of the biological base of resilience could be added in a multidimensional/multifactorial model to help researchers identify ways to promote resiliency even before birth. PMID- 17347372 TI - Resilience among at-risk Hispanic American preschool children. AB - This study combines cognitive (i.e., intelligence), psychosocial (i.e., inhibition, activity level, negative emotionality, emotion regulation, autonomy), and cultural-linguistic factors (i.e., level of acculturation and bilingualism) to determine patterns of resilience and vulnerability among 207 economically disadvantaged Hispanic American preschool children, from 50 early childhood classrooms, as gauged by their social competence during peer play. Person oriented analysis yielded six distinct profiles, two profiles of which were resilient and one identified as vulnerable. Results of this study revealed within group differences in resilience among these children and the significant role bilingualism and maintenance of the home language play in their social-emotional development. PMID- 17347373 TI - Pathways of adaptation from adolescence to young adulthood: antecedents and correlates. AB - This study examines longitudinal change using a person-centered approach to differentiate patterns of adaptive functioning from adolescence to adulthood. Data are drawn from a 20-year longitudinal study of competence and resilience in the lives of 205 school children (29% minority). Results indicate five distinct pathways of adaptation: (1) low-declining, (2) low-improving, (3) middle improving, (4) middle-declining, and (5) consistently high. The study also compares the five groups on childhood risks and resources, and on longitudinal assessment of competence and adversity. Interestingly, the most dramatic changes in pathways of adaptation occur during the period of emerging adulthood. PMID- 17347374 TI - Relational and academic components of resilience in maltreated adolescents. AB - This study examines the components of resilience in adolescents (aged 11-15 years; n = 816) who were referred to the child welfare system for maltreatment. Data from a national probability study of children and families in the child welfare system showed that adolescents faced a number of risk factors like maltreatment, poverty, and exposure to violence in the community. Social competence, academic achievement, and a sense of relatedness to caregiver were fit in a structural equation model as components of latent resilience. Social competence and the quality of relationship with a caregiver were strongly linked to latent resilience. PMID- 17347375 TI - Using protective factors in practice: lessons learned about resilience from a study of children aged five to thirteen. AB - There are many advantages of using resilience as a framework to guide the screening, assessment, and promotion of social-emotional health in children. This article reviews which individual attributes are most important for the resilience of elementary school-age children, as primarily determined by the positive attribute's ability to discriminate between typically developing children and those with disciplinary, mental health, and/or special education referrals or services. This research lends itself to a practical framework to scientifically measure and utilize individual social-emotional strengths for the purposes of fostering resilience in all children. PMID- 17347377 TI - Neighborhood risk and the development of resilience. AB - The purpose of the study was to advance our understanding of resilience by studying multiple protective factors associated with positive adjustment among an ethnically diverse sample of 310 low-income boys followed prospectively from ages 1.5 to 12 years, using neighborhood quality to define risk status. The results indicated that child and family protective factors measured in early childhood were all significantly associated with positive adjustment at 11 and 12 years of age. However, these results were qualified by risk level, such that parent-child relationship quality was only significantly related to positive outcomes in the context of low levels of risk. PMID- 17347376 TI - Prenatal cocaine exposure: cardiorespiratory function and resilience. AB - Cardiac vagal tone (VT) was studied as a resilience factor in children prenatally exposed to cocaine and nonexposed controls (n = 550). A cumulative risk index was derived and used to classify children as high versus low risk. VT was measured during mildly stressful observations at 1 and 36 months of age. Children were classified as having consistently high, consistently low, or fluctuating VT. Risk and VT interacted to predict adaptive behaviors. For high-risk children, low VT was related to higher ratings of adaptive behaviors. This finding suggests that regulatory functioning, as indexed by VT, may be a protective factor in prenatal CE. PMID- 17347378 TI - Association of direct exposure to terrorism, media exposure to terrorism, and other trauma with emotional and behavioral problems in preschool children. AB - This study examined the differential impact of various types of trauma exposure on emotional and behavioral problems in preschool children. Participants were 95 mothers of 1- to 4-year-old children in Israel. Results suggested a differential pattern of associations between the types of trauma exposure (i.e., direct exposure to terrorism, media exposure to terrorism, and other trauma) and children's internalizing and externalizing problems. This line of research is important for the identification of risk factors and the development of effective prevention and intervention strategies to promote resilience in preschool children exposed to specific type(s) of trauma. PMID- 17347379 TI - Myocardial infarct size measurement in the mouse chronic infarction model: comparison of area- and length-based approaches. AB - Efficacy of potential treatments for myocardial infarction (MI) is commonly assessed by histological measurement of infarct size in rodent models. In experiments involving an acute MI setting, measurement of the infarcted area in tissue sections of the left ventricle is a standard approach to determine infarct size. This approach has also been used in the chronic infarct setting to measure infarct area several weeks post-MI. We tested the hypothesis that, because wall thinning is known to occur in the chronic setting, the area measurement approach would be less appropriate. We compared infarct measurements in tissue sections based on 1) infarct area, 2) epicardial and endocardial infarct arc lengths, and 3) midline infarct arc length. Infarct sizes from all three measurement approaches correlated significantly with left ventricular ejection fraction and wall motion abnormality. However, the infarct size values derived from the area measurement approach were significantly smaller than those from the other two measurement approaches, and the range of values obtained was compressed 0.4-fold. The midline method allowed detection of the expected size differences between infarcts of variable severity resulting from proximal vs. distal ligation of the coronary artery. Segmental infarct size was correlated with segmental wall motion abnormality. We conclude that both area- and length-based measurements can be used to determine relative infarct size over a wide range of severity, although the area-based measurements are substantially more compressed due to wall thinning, and that the estimation of infarct midlines is a simple, reliable approach to infarct size assessment. PMID- 17347380 TI - Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy. AB - Creatine (Cr) levels in skeletal muscle and brain of a mouse model of Cr deficiency caused by guanidinoacetate methyltransferase absence (GAMT-/-) were studied after Cr supplementation with 2 g.kg body wt-1.day-1 Cr for 35 days. Localized 1H magnetic resonance spectroscopy (MRS) was performed in brain (cerebellum and thalamus/hippocampus) and in hind leg muscle of GAMT-/- mice before and after Cr supplementation and in control (Con) mice. As expected, a signal for Cr was hardly detectable in MR spectra of GAMT-/- mice before Cr supplementation. In the thalamus/hippocampus region of these mice, an increase in N-acetylasparate (NAA) was observed. During Cr administration, Cr levels increased faster in skeletal muscle compared with brain, but this occurred only during the first day of supplementation. Thereafter, Cr levels increased by 0.8 mM/day in all studied locations. After 35 days of Cr supplementation, Cr levels in all locations were higher compared with Con mice on a Cr-free diet and NAA levels normalized. Only because of the repeated MRS measurements performed in this longitudinal Cr supplementation study on GAMT-/- mice were we able to discover the initial faster uptake of Cr in skeletal muscle compared with brain, which may represent muscular Cr uptake independent of Cr transporter expression. Our results can provide the basis for additional experiments to optimize Cr supplementation in GAMT deficiency, as increases in brain Cr are slow in patients after Cr supplementation. PMID- 17347381 TI - Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans. AB - Genetic variation in myostatin, a negative regulator of skeletal muscle, in cattle has shown remarkable influence on skeletal muscle, resulting in a double muscled phenotype in certain breeds; however, DNA sequence variation within this gene in humans has not been consistently associated with skeletal muscle mass or strength. Follistatin and activin-type II receptor B (ACVR2B) are two myostatin related genes involved in the regulation and signaling of myostatin. We sought to identify associations between genetic variation and haplotype structure in both follistatin and ACVR2B with skeletal muscle-related phenotypes. Three hundred fifteen men and 278 women aged 19-90 yr from the Baltimore Longitudinal Study of Aging were genotyped to determine respective haplotype groupings (Hap Groups) based on HapMap data. Whole body soft tissue composition was measured by dual energy X-ray absorptiometry. Quadriceps peak torque (strength) was measured using an isokinetic dynamometer. Women carriers of ACVR2B Hap Group 1 exhibited significantly less quadriceps muscle strength (shortening phase) than women homozygous for Hap Group 2 (109.2+/-1.9 vs. 118.6+/-4.1 N.m, 30 degrees/s, respectively, P=0.036). No significant association was observed in men. Male carriers of follistatin Hap Group 3 exhibited significantly less total leg fat free mass than noncarriers (16.6+/-0.3 vs. 17.5+/-0.2 kg, respectively, P=0.012). No significant associations between these haplotype groups were observed in women. These results indicate that haplotype structure at the ACVR2B and follistatin loci may contribute to interindividual variation in skeletal muscle mass and strength, although these data indicate sex-specific relationships. PMID- 17347382 TI - Genetic variation of the beta2-adrenergic receptor is associated with differences in lung fluid accumulation in humans. AB - The beta2-adrenergic receptors (beta2AR) play an important role in lung fluid regulation. Previous research has suggested that subjects homozygous for arginine at amino acid 16 of the beta2AR (Arg16) may have attenuated receptor function relative to subjects homozygous for glycine at the same amino acid (Gly16). We sought to determine if the Arg16Gly polymorphism of the beta2AR influenced lung fluid balance in response to rapid saline infusion. We hypothesized that subjects homozygous for Arg at amino acid 16 (n=14) would have greater lung fluid accumulation compared with those homozygous for Gly (n=15) following a rapid intravenous infusion of isotonic saline (30 ml/kg over 17 min). Changes in lung fluid were determined using measures of lung density and tissue volume (computerized tomography imaging) and measures of pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (DM, determined from the simultaneous assessment of the diffusing capacities of the lungs for carbon monoxide and nitric oxide). The saline infusion resulted in elevated catecholamines in both genotype groups (Arg16 283+/-117% vs. Gly16 252+/-118%, P>0.05). The Arg16 group had a larger decrease in DM and increase in lung tissue volume and lung water after saline infusion relative to the Gly16 group (DM -13+/ 14 vs. 0+/-26%, P<0.05; lung tissue volume 13+/-11 vs. 3+/-11% and lung water +90+/-66 vs. +48+/-144 ml, P=0.10, P<0.05, for Arg vs. Gly16, respectively, means+/-SD). These data suggest that subjects homozygous for Arg at amino acid 16 of the beta2AR have a greater susceptibility for lung fluid accumulation relative to subjects homozygous for Gly at this position. PMID- 17347383 TI - Microvascular and capillary perfusion following glycocalyx degradation. AB - Systemic parameters and microvascular and capillary hemodynamics were studied in the hamster window chamber model before and after hyaluronan degradation by intravenous injection of Streptomyces hyaluronidase (100 units, 40-50 U/ml plasma). Glycocalyx permeation was estimated using fluorescent markers of different molecular size (40, 70, and 2,000 kDa), and electrical charge. Systemic parameters (blood pressure, heart rate, blood gases) and microhemodynamics (vascular tone, velocity, and blood flow) remained statistically unchanged after injection of hyaluronidase, compared with inactivated hyaluronidase. Conversely, capillary hemodynamics were drastically affected. Functional capillary density, the capillaries perfused with red blood cells (RBCs), decreased by 35%, capillary Hct of the remaining functional capillaries increased from 16 to 27%, and penetration of 70-kDa fluorescent marker increased. Furthermore, plasma-only perfused capillaries statistically increased 30 min after hyaluronidase. The decrease in functional capillary density accounted for an increased RBC flux in the remainder of the capillaries, since the same number of RBCs had to traverse a reduced number of capillaries. Flux balances showed a reduction from baseline of 11% for the RBC flux and 20% for the plasma flux after treatment. These discrepancies are within the margin of error of the techniques used and could be explained by accounting for RBC over-velocity compared with plasma. These findings suggest that the decrease in the glycocalyx leads to capillary perfusion impairments. PMID- 17347384 TI - Changes in stretch reflexes and muscle stiffness with age in prepubescent children. AB - Musculo-articular stiffness of the triceps surae (TS) increases with age in prepubescent children, under both passive and active conditions. This study investigates whether these changes in muscle stiffness influence the amplitude of the reflex response to muscle stretch. TS stiffness and reflex activities were measured in 46 children (7-11 yr old) and in 9 adults. The TS Hoffmann reflex (H reflex) and T reflex (tendon jerk) in response to taping the Achilles tendon were evaluated at rest and normalized to the maximal motor response (Mmax). Sinusoidal perturbations of passive or activated muscles were used to evoke stretch reflexes and to measure passive and active musculoarticular stiffness. The children's Hmax to-Mmax ratio did not change with age and did not differ from adult values. The T to-Mmax ratio increased with age but remained significantly lower than in adults. Passive stiffness also increased with age and was correlated with the T-to-Mmax ratio. Similarly, the children's stretch reflex and active musculoarticular stiffness were significantly correlated and increased with age. We conclude that prepubescent children have smaller T reflexes and stretch reflexes than adults, and the lower musculoarticular stiffness is mainly responsible for these smaller reflexes, as indicated by the parallel increases in reflex and stiffness. PMID- 17347385 TI - Quantitative assessments of morphological and functional properties of biological trees based on their fractal nature. AB - The branching systems in our body (vascular and bronchial trees) and those in the environment (plant trees and river systems) are characterized by a fractal nature: the self-similarity in the bifurcation pattern. They increase their branch density toward terminals according to a power function with the exponent called fractal dimension (D). From a stochastic model based-on this feature, we formulated the fractal-based integrals to calculate such morphological parameters as aggregated branch length, surface area, and content volume for any given range of radius (r). It was followed by the derivation of branch number and cross sectional area, by virtue of the logarithmic sectioning of the r axis and of the branch radius-length relation also given by a power function of r with an exponent (alpha). These derivatives allowed us to quantify various hydrodynamic parameters of vascular and bronchial trees as fluid conduit systems, including the individual branch flow rate, mean flow velocity, wall shear rate and stress, internal pressure, and circumferential tension. The validity of these expressions was verified by comparing the outcomes with actual data measured in vivo in the vascular beds. From additional analyses of the terminal branch number, we found a simple equation relating the exponent (m) of the empirical power law (Murray's so called cube law) to the other exponents as (m=D+alpha). Finally, allometric studies of mammalian vascular trees revealed uniform and scale-independent distributions of terminal arterioles in organs, which afforded an infarct index, reflecting the severity of tissue damage following arterial infarction. PMID- 17347386 TI - Exercise-induced suppression of acylated ghrelin in humans. AB - Ghrelin is an orexigenic hormone secreted from endocrine cells in the stomach and other tissues. Acylation of ghrelin is essential for appetite regulation. Vigorous exercise induces appetite suppression, but this does not appear to be related to suppressed concentrations of total ghrelin. This study examined the effect of exercise and feeding on plasma acylated ghrelin and appetite. Nine male subjects aged 19-25 yr participated in two, 9-h trials (exercise and control) in a random crossover design. Trials began at 0800 in the morning after an overnight fast. In the exercise trial, subjects ran for 60 min at 72% of maximum oxygen uptake between 0800 and 0900. After this, they rested for 8 h and consumed a test meal at 1100. In the control trial, subjects rested for 9 h and consumed a test meal at 1100. Area under the curve values for plasma acylated ghrelin concentration (assessed from venous blood samples) were lower over the first 3 h and the full 9 h of the exercise trial compared with the control trial: 317+/-135 vs. 510+/-186 pg.ml(-1).3 h and 917+/-342 vs. 1,401+/-521 pg.ml(-1).9 h (means+/ SE) respectively (P<0.05). Area under the curve values for hunger (assessed using a visual scale) were lower over the first 3 h of the exercise trial compared with the control trial (P=0.013). These findings demonstrate that plasma acylated ghrelin concentration and hunger are suppressed during running. PMID- 17347387 TI - Role of myokines in exercise and metabolism. AB - During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an "exercise factor," which could mediate some of the exercise induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as "myokines." Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named "myokines." Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines. PMID- 17347388 TI - Demographic factors associated with prevalence of antibody to Sin Nombre virus in deer mice in the western United States. AB - We used long-term data collected for up to 10 yr (1994-2004) at 23 trapping arrays (i.e., webs and grids) in Arizona, Colorado, Montana, and New Mexico to examine demographic factors known or suspected to be associated with risk of infection with Sin Nombre virus (SNV) in its natural host, the deer mouse (Peromyscus maniculatus). Gender, age (mass), wounds or scars, season, and local relative population densities were statistically associated with the period prevalence of antibody (used as a marker of infection) to SNV in host populations. Nevertheless, antibody prevalence and some of the risk factors associated with antibody prevalence, such as relative population density, gender bias, and prevalence of wounding, varied significantly among sites and even between nearby trapping arrays at a single site. This suggests that local microsite-specific differences play an important role in determining relative risk of infection by SNV in rodents and, consequently, in humans. Deer mouse relative population density varied among sites and was positively and statistically associated with infection prevalence, an association that researchers conducting shorter-term studies failed to demonstrate. Both wounding and antibody prevalence increased with mass class in both males and females; this increase was much more pronounced in males than in females and wounding was more frequent in adult males than in adult females. Prevalence of wounding was greatest among seropositive deer mice, regardless of mass class, but many deer mice without detectable wounds or scars eventually became infected. Many of these patterns, which will be useful in the development of predictive models of disease risk to humans, were only detected through the application of data collected over a long (10-yr) period and with abundant replication. PMID- 17347389 TI - Sin Nombre virus infection of deer mice in Montana: characteristics of newly infected mice, incidence, and temporal pattern of infection. AB - Sin Nombre virus (SNV), hosted by the deer mouse (Peromyscus maniculatus), is the principal cause of hantavirus pulmonary syndrome (HPS) in North America. To improve our understanding of factors that contribute to the occurrence of HPS, we conducted an extensive field study of the characteristics of newly infected (as determined by recent acquisition of antibody) deer mice and the temporal pattern of antibody acquisition (seroconversion) from 1994 through 2004 in Montana, USA. We sampled 6,584 individual deer mice, of which 2,747 were captured over multiple trapping periods. Among these 2,747 deer mice, we detected 171 instances of seroconversion. There was no relationship between seroconversion and the acquisition of scars. However, recently infected Montana deer mice were more likely to be older, more likely to be males, and more likely to be in breeding condition. In addition, recently infected male deer mice gained less weight over the 1-mo period following seroconversion than did those that did not acquire antibody, suggesting that SNV infection may have negatively impacted the health of infected rodents. Incidence was highly variable among years, and timing of infections was primarily associated with the breeding season (generally early spring through late fall). PMID- 17347390 TI - Tularemia in deer mice (peromyscus maniculatus) during a population irruption in Saskatchewan, Canada. AB - Type B tularemia caused by Francisella tularensis subsp. holarctica was diagnosed in deer mice (Peromyscus maniculatus) found dead at four sites in west-central Saskatchewan during April and May 2005. The occurrence of tularemia coincided with a decline in the number of deer mice in part of a large area (>22000 km(2) ) in which deer mice had been extremely abundant during the autumn of 2004 and spring of 2005, and in which mice caused damage to crops in the autumn of 2004. This is apparently the first report of tularemia as a cause of death of wild deer mice. The bacterium isolated from deer mice was atypical in that cysteine was not required in the media used for isolation. Three isolates tested were genotypes not previously identified in Canada. There were no reports of human disease in the area. PMID- 17347391 TI - The dynamics of murid gammaherpesvirus 4 within wild, sympatric populations of bank voles and wood mice. AB - Murid gammaherpesvirus 4 (MuHV-4) is widely used as a small animal model for understanding gammaherpesvirus infections in man. However, there have been no epidemiological studies of the virus in wild populations of small mammals. As MuHV-4 both infects cells associated with the respiratory and immune systems and attempts to evade immune control via various molecular mechanisms, infection may reduce immunocompetence with potentially serious fitness consequences for individuals. Here we report a longitudinal study of antibody to MuHV-4 in a mixed assemblage of bank voles (Clethrionomys glareolus) and wood mice (Apodemus sylvaticus) in the UK. The study was conducted between April 2001 and March 2004. Seroprevalence was higher in wood mice than bank voles, supporting earlier work that suggested wood mice were the major host even though the virus was originally isolated from a bank vole. Analyses of both the probability of having antibodies and the probability of initial seroconversion indicated no clear seasonal pattern or relationship with host density. Instead, infection risk was most closely associated with individual characteristics, with heavier males having the highest risk. This may reflect individual variation in susceptibility, potentially related to variability in the ability to mount an effective immune response. PMID- 17347392 TI - Assessing flavivirus, lentivirus, and herpesvirus exposure in free-ranging ring tailed lemurs in southwestern Madagascar. AB - The ring-tailed lemur (Lemur catta) is an endangered species found in southwestern Madagascar, and understanding infectious disease susceptibility is an essential step towards the preservation of wild and captive lemur populations. Lemurs are primates that are widely dispersed throughout the island of Madagascar and may serve as hosts or reservoirs for zoonotic infections. The aim of this study was to determine the prevalence of antibodies to West Nile virus (WNV), simian immunodeficiency virus (SIV), and herpes simplex virus type 1 (HSV-1) in a population of free-ranging ring-tailed lemur from the Beza Mahafaly Special Reserve, Madagascar. Samples were collected from 50 animals during field capture studies in June and July 2004 and assayed for presence of viral antibodies during the 12 mo following collection. Forty-seven of the 50 lemurs sampled had antibodies against WNV detectable by epitope-blocking enzyme-linked immunosorbent assay (ELISA). In addition, 50 of 50 samples had titers against WNV ranging from 80 to > or = 1,280 using plaque reduction neutralization test (PRNT(90)). Ten lemurs had antibodies against lentiviral antigens as determined by Western blot analysis. None of the lemurs had antibodies against HSV-1 using ELISA. PMID- 17347393 TI - Surveillance for batrachochytrium dendrobatidis using Mixophyes (Anura: Myobatrachidae) larvae. AB - Fourteen populations of anuran larvae (tadpoles), including three populations of the endangered Fleay's Barred Frog (Mixophyes fleayi) and 11 populations of the common Great Barred Frog (Mixophyes fasciolatus), in creek sites in the southeast region of Queensland were selected. Site selection was based on a history (within the district) of adult frog population declines and/or disappearances or records of infection of adult frogs or larvae by Batrachochytrium dendrobatidis. Larvae were collected once from each creek site between October 2002 and October 2004, and were between Gosner developmental stages 25 and 40. Total body length ranged from 18 mm to 100 mm. Mouthparts were examined under a dissecting microscope for grossly visible abnormalities, and then examined for histologic evidence of B. dendrobatidis. The most consistent mouthpart abnormalities found were multifocal depigmentation of the jaw sheaths and loss or shortening of the tooth rows. At the individual larva level, presence of mouthpart abnormalities was strongly associated with histologic diagnosis of B. dendrobatidis (93%). At least one larva with abnormal mouthparts was detected at 12 of the 14 sites and histologic evidence of B. dendrobatidis was detected at 13 of the 14 sites. These findings suggest that larvae of Mixophyes species are suitable for surveillance for B. dendrobatidis. We conclude that surveillance of B. dendrobatidis where individual larva prevalences of mouthpart abnormalities and histologic evidence of B. dendrobatidis are as high as those observed in this study (66% and 78%, respectively), relatively small numbers of larvae are required to detect these infections. Medium to large larvae (body length >30 mm) were much more likely to be affected than small larvae (body length < or =30 mm), suggesting that larger individuals should be targeted for surveillance. PMID- 17347394 TI - Mineral deficiencies in tule elk, Owens Valley, California. AB - Male tule elk (Cervus elaphus nannodes) are susceptible to high rates of antler breakage in Owens Valley, California. We hypothesized that a mineral deficiency in the diet predisposed male elk to antler breakage. We analyzed elk antler, liver, and forage samples to identify mineral imbalances. We compared the mineral content of livers and antlers from elk in Owens Valley to samples taken from tule elk at Grizzly Island Wildlife Area, a population experiencing normal rates (<5%) of antler breakage. Antler and liver samples were collected from 1989 to 1993, and in 2002, and were tested for calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), phosphorus (P), sulfur (S), and zinc (Zn). Mineral levels from antler and liver samples were compared to reference values established for elk and deer. We also compared the mineral content of elk forage in Owens Valley, collected in 2002-03, to dietary reference values established for cattle. In antlers, Ca, Fe, and Mg levels were higher in Owens Valley elk than in Grizzly Island elk, although all mineral levels were lower than reference values established for deer antlers. In liver samples, Cu levels from elk in Owens Valley were lower than those from Grizzly Island and lower than minimum reference values; liver Ca and Mo levels were higher in elk from Owens Valley than in those from Grizzly Island. Compared to reference values, elk forage in Owens Valley had high levels of Ca and Mo, and low levels of Cu, P, and Zn. Mineral analyses from antlers, livers, and forage suggest that tule elk in the Owens Valley are Cu and/or P deficient. High levels of Mo and Ca may exacerbate Cu and P deficiencies, respectively. Bone fragility is a symptom of both deficiencies, and an imbalance in Cu, P, or a combination of both, may predispose male tule elk in the Owens Valley to antler breakage. PMID- 17347395 TI - Mannheimia (Pasteurella) haemolytica leukotoxin utilizes CD18 as its receptor on bighorn sheep leukocytes. AB - Pneumonia caused by Mannheimia (Pasteurella) haemolytica is a highly fatal disease of bighorn sheep (Ovis canadensis). Leukotoxin (Lkt), secreted by M. haemolytica, is an important virulence factor of this organism, and is cytolytic to bighorn sheep leukocytes. Previously, we have shown that CD18, the beta subunit of beta2 integrins, serves as the receptor for Lkt on bovine leukocytes. Furthermore, anti-CD18 antibodies inhibit Lkt-induced cytotoxicity of bighorn sheep leukocytes. Therefore, we hypothesized that Lkt utilizes CD18 as its receptor on bighorn sheep leukocytes. Confirmation of bighorn sheep CD18 as a receptor for Lkt requires the demonstration that the recombinant expression of bighorn sheep CD18 in Lkt-nonsusceptible cells renders them susceptible to Lkt. Therefore, we transfected cDNA encoding CD18 of bighorn sheep into a Lkt nonsusceptible murine cell line. Cell surface expression of bighorn sheep CD18 on the transfectants was tested by flow cytometry with anti-CD18 antibodies. Transfectants stably expressing bighorn sheep CD18 on their surface were subjected to flow cytometric analysis for detection of Lkt binding, and cytotoxicity assays for detection of Lkt-induced cytotoxicity. Leukotoxin bound to the transfectants. More importantly, the transfectants were effectively lysed by Lkt in a concentration-dependent manner, whereas the parent cells were not. These results clearly indicate that M. haemolytica Lkt utilizes CD18 as a receptor on bighorn sheep leukocytes. Identification of CD18 as a receptor for Lkt on bighorn sheep leukocytes should enhance our understanding of the pathogenesis of pneumonia, which in turn should help in the development of control measures against this fatal disease of bighorn sheep. PMID- 17347396 TI - Detection of Dichelobacter nodosus in wild ungulates (Capra ibex ibex and Ovis aries musimon) and domestic sheep suffering from foot rot using a two-step polymerase chain reaction. AB - Severe keratinous hoof afflictions have been recorded in ibex (Capra ibex ibex) since 1995 and more recently in mouflon (Ovis aries musimon) in Switzerland. Based on clinical observations and comparison with diseases known to affect domestic ungulates, it was hypothesized these wild ungulates were affected by foot rot associated with infection with Dichelobacter nodosus. Dichelobacter nodosus has been shown to be the essential pathogen for initiation and establishment of foot rot, a highly contagious foot disease of sheep and goats. Because these bacteria could not be cultivated from affected ibex, we developed a nested polymerase chain reaction that allowed detection of D. nodosus without culture. Using this assay, we were able to diagnose D. nodosus infections of ibex, mouflon, and domestic sheep in natural outbreaks. From these results we conclude that D. nodosus plays an etiological role in foot rot not only in domestic but also in wild Caprinae. PMID- 17347397 TI - New variants of European brown hare syndrome virus strains in free-ranging European brown hares (Lepus europaeus) from Slovakia. AB - Investigations regarding European brown hare syndrome virus (EBHSV) in European brown hares (Lepus europaeus) in Slovakia were undertaken in order to detect the possible presence of EBHSV and to evaluate its phylogenetic position. Liver and/or serum samples were obtained from 135 European brown hares shot by hunters in eight regional hunting areas. From 36 animals corresponding liver and serum samples were available; from the remaining 49 and 50 animals only liver or serum samples were examined, respectively. Samples were tested for antibodies against EBHSV and for viral RNA by reverse transcriptase-polymerase chain reaction (RT PCR) and RT-PCR products were subsequently sequenced. Additionally, matrilinear hare haplotypes were analyzed in order to detect potential familial susceptibility to EBHSV. Sixty-three of 86 sera contained antibodies against EBHSV, whereas 15 of 85 liver samples were PCR positive. Of the latter, 14 were sequenced, revealing three new strains of EBHSV. Fifteen different matrilinear haplotypes were identified, but no correlation was found between haplotype and susceptibility to EBHSV infection. Our findings confirmed the existence of EBHSV in Slovakia and reinforce the need for determining EBHSV status when importing hares for restocking. PMID- 17347398 TI - Oral rabies vaccine (ORV) bait uptake by captive striped skunks. AB - Aerial delivery of oral rabies vaccine (ORV) baits has proven effective in large scale efforts to immunize wildlife against rabies, and in North America this strategy currently is being used to immunize foxes (Urocyon cinereoargenteus and Vulpes vulpes), raccoons (Procyon lotor), and coyotes (Canis latrans). Skunks are also a major reservoir and vector of rabies, but at present oral vaccines for use in skunks are not licensed. Furthermore, given differences in morphology (smaller jaws) and behavior (food handling and consumption), it is unknown if baits currently used in ORV campaigns would be effective for skunks. Because oral vaccine delivery is contingent upon puncture of the vaccine container (VC), baits need to be sufficiently attractive to elicit selection and consumption. Manipulation of the bait to facilitate vaccine ingestion by the target species is a critical element for an effective ORV bait. The objectives of this study were to assess manipulation and consumption of current ORV baits by striped skunks (Mephitis mephitis). We conducted four independent trials with penned animals and various baits to assess bait selection frequency, VC puncture frequency, and consumption. Video recorded trials were used to assess attractiveness of baits and consumption behavior of skunks. Bait characteristics, such as texture, size, and flavor influenced selection and consumption. Fish and chicken flavors were preferred and vaccine containers within selected baits were likely to be punctured. Vaccine ingestion seemed more likely if VCs were directly coated with the bait matrix. To make baits attractive to skunks and to ensure puncture of the VC, modifications to current baits should consider a smaller size, a meat flavored matrix, a slightly pressurized VC, and a direct coating of matrix on the VC. PMID- 17347399 TI - Serratia marcescens infection in a swallow-tailed hummingbird. AB - A swallow-tailed hummingbird (Eupetomena macroura) was presented with a history of prostration and inability to fly. After a 2-day hospitalization, the bird died and necropsy findings included diffuse hyperemia of the small intestine serosal and mucosal surfaces and the presence of a small quantity of clear ascitic fluid in the coelomic cavity. Intestinal contents and cardiac blood were collected for microbiologic exams yielding pure cultures of a pigmented strain of Serratia marcescens. This strain was susceptible to gentamicin, enrofloxacin, streptomycin, trimethoprim, and sulfamethoxazole and had intermediate susceptibility to chloramphenicol and resistance to cephalotin. The source of the infection could not be ascertained, but possible contamination of hummingbird feeders could be involved, because the infection seemed to originate from the digestive tract. PMID- 17347400 TI - Gross and microscopic pathology associated with large cavernous lesions in muscle of Chinook salmon from Lake Ontario. AB - Since 1999, eight adult Chinook salmon (Onchorhynchus tshawytscha) from Lake Ontario with large, focal, cavernous, fluid-filled muscle lesions have been examined in our respective laboratories. Gross and microscopic examination, cytology, and bacteriology were performed. Microscopically the lesions were consistent with chronic abscesses. Cytologic evaluation revealed diplomonad flagellate Spironucleus within these lesions. We provide a description of the gross and microscopic pathology associated with the cavernous lesions. PMID- 17347401 TI - Does human proximity affect antibody prevalence in marine-foraging river otters (Lontra canadensis)? AB - The investigation of diseases of free-ranging river otters (Lontra canadensis) is a primary conservation priority for this species; however, very little is known about diseases of river otters that forage in marine environments. To identify and better understand pathogens that could be important to marine-foraging river otters, other wildlife species, domestic animals, and humans and to determine if proximity to human population could be a factor in disease exposure, serum samples from 55 free-ranging marine-foraging river otters were tested for antibodies to selected pathogens. Thirty-five animals were captured in Prince William Sound, Alaska (USA), an area of low human density, and 20 were captured in the San Juan Islands, Washington State (USA), an area characterized by higher human density. Of 40 river otters tested by indirect immunofluorescent antibody test, 17.5% were seropositive (titer > or =320) for Toxoplasma gondii. All positive animals came from Washington. Of 35 river otters tested for antibodies to Leptospira interrogans using the microscopic agglutination test, 10 of 20 (50%) from Washington were seropositive (titer > or =200). None of the 15 tested animals from Alaska were positive. Antibodies to Neospora caninum (n=40), Sarcocystis neurona (n=40), Brucella abortus (n=55), avian influenza (n=40), canine distemper virus (n=55), phocine distemper virus (n=55), dolphin morbillivirus (n=55), porpoise morbillivirus (n=55), and Aleutian disease parvovirus (n=46) were not detected. Identifying exposure to T. gondii and L. interrogans in otters from Washington State but not in otters from Alaska suggests that living proximal to higher human density and its associated agricultural activities, domestic animals, and rodent populations could enhance river otter exposure to these pathogens. PMID- 17347402 TI - Rabies challenge of captive striped skunks (Mephitis mephitis) following oral administration of a live vaccinia-vectored rabies vaccine. AB - Twenty-four adult striped skunks (Mephitis mephitis) were administered the raccoon product formulation of Rabies Vaccine, Live Vaccinia-Vectored (Raboral V RG, Merial Limited, Athens, Georgia, USA), either by oral instillation or in vaccine-filled coated sachets either as single or multiple doses. A control group remained unvaccinated. Twenty-three of the skunks were challenged 116 days postvaccination with rabies virus (skunk isolate). Six of six naive skunks succumbed to challenge. Four of six skunks that received the vaccine by oral instillation survived challenge. The skunks that did not survive failed to seroconvert following vaccination. None of the skunks that accepted multiple doses of the vaccine offered in coated sachets survived challenge, nor were rabies virus-neutralizing antibodies (VNAs) detected in the sera. Likewise, none of the five skunks ingesting a single sachet developed VNA against rabies. However, in this group one skunk did survive rabies challenge. This preliminary study showed that the vaccinia-vectored oral rabies vaccine Raboral V-RG, as formulated for use in raccoons, is capable of protecting a percentage of skunks against rabies. However, although the fishmeal-coated sachets were readily consumed, subsequent challenge of these animals revealed poor vaccine delivery efficiency. PMID- 17347403 TI - Necropsy findings and arbovirus surveillance in mourning doves from the southeastern United States. AB - Mourning doves (Zenaida macroura) are the most abundant and widespread native member of the columbid family, as well as a major migratory game species, in the United States. However, there is little information on mortality factors in mourning doves. Records of necropsy accessions at the Southeastern Cooperative Wildlife Disease Study (SCWDS) from 15 southeastern states, from 1971 through 2005, were reviewed. One hundred thirty-five mourning doves were submitted from nine states during the 35-yr period. Trichomonosis constituted 40% (n = 54) of all diagnoses and was the most frequent diagnosis. Toxicoses and avian pox constituted 18.5% (n = 25) and 14.8% (n = 20) of all diagnoses, respectively. Remaining diagnoses included trauma, suspected toxicosis, Ascaridia columbae infection, suspected tick paralysis, and undetermined. Adults were observed more frequently with trichomonosis (94.1%) and toxicoses (68%) as compared to juveniles, but a gender predisposition was not apparent for either disease. Age and gender predilections were not apparent for cases of avian pox. The majority of the trichomonosis and avian pox cases were observed in the spring-summer, whereas the majority of the toxicosis cases were observed in the winter-spring. Additionally, the Georgia Department of Human Resources-Division of Public Health and West Virginia Department of Health and Human Resources submitted 809 mourning doves to SCWDS from 2001 through 2005 for West Nile virus surveillance efforts. West Nile virus was isolated from 2.1% (n = 17) and eastern equine encephalitis virus (EEEV) was isolated from 0.2% (n = 2) of the submitted birds. PMID- 17347404 TI - First detection of Bacillus anthracis in feces of free-ranging raptors from central Argentina. AB - Prevalence of anthrax spores in feces of raptors was determined from samples collected in November-December 2000 and April-May 2001 in an agricultural region of Santa Fe province, Argentina. Feces were tested from 48 birds of six raptor species. One of 14 chimango caracaras (Milvago chimango) and one of eight road side hawks (Buteo magnirostris) tested positive. The prevalence of Bacillus anthracis spores in feces for the six species was 4% (n=48). The prevalence was 7% (n=14) for chimango caracaras, 13% for road-side hawks (n=8), and 0% for the remaining species (Burrowing owl [Speotyto cunicularia] [n=17], Swainson's hawk [Buteo swainsoni] [n=3], Aplomado falcon [Falco femoralis] [n=2], and American kestrel [Falco sparverius] [n=4]). Grouped by their feeding habits, prevalence for scavenger species was not significantly different than for predators (7% vs. 3%, P>0.999). This study provides evidence that in central Argentina scavenger and non-scavenger raptors may have a role in the epidemiology of anthrax. Long term studies to determine the extent of this potential involvement in the epidemiology of anthrax in central Argentina are required. PMID- 17347405 TI - First observation of Elaeophora schneideri Wehr and Dikmans, 1935 (Nematoda:Filariidae) in mule deer from Nebraska. AB - Between November 2000 and November 2005, approximately 200 mule deer (Odocoileus hemionus hemionus) and white-tailed deer (Odocoileus virginianus) from western Nebraska were extensively examined for the presence of Elaeophora schneideri, Wehr and Dikmans, 1935; three adult E. schneideri were detected from three mule deer. This represents the first documented occurrence of E. schneideri from wild deer in Nebraska. PMID- 17347406 TI - Homeostatic expansion and repertoire regeneration of donor T cells during graft versus host disease is constrained by the host environment. AB - Graft versus host disease (GVHD) typically results in impaired T-cell reconstitution characterized by lymphopenia and repertoire skewing. One of the major causes of inadequate T-cell reconstitution is that T-cell survival and expansion in the periphery are impaired. In this report, we have performed adoptive transfer studies to determine whether the quantitative reduction in T cell numbers is due to an intrinsic T-cell defect or whether the environmental milieu deleteriously affects T-cell expansion. These studies demonstrate that T cells obtained from animals with graft-versus-host disease (GVHD) are capable of significant expansion and renormalization of an inverted CD4/CD8 ratio when they are removed from this environment. Moreover, these cells can generate complex T cell repertoires early after transplantation and are functionally competent to respond to third-party alloantigens. Our data indicate that T cells from mice undergoing GVHD can respond to homeostatic signals in the periphery and are not intrinsically compromised once they are removed from the GVHD environment. We thereby conclude that the host environment and not an intrinsic T-cell defect is primarily responsible for the lack of effective T-cell expansion and diversification of complex T-cell repertoires that occurs during GVHD. PMID- 17347407 TI - Role of BCR/ABL gene-expression levels in determining the phenotype and imatinib sensitivity of transformed human hematopoietic cells. AB - Increased levels of Bcr-Abl expression in chronic myelogenous leukemia (CML) cells are associated with disease progression and imatinib (IM) resistance. However, it is not clear if these associations are a direct result of elevated Bcr-Abl expression. We used a human transduction model of CML to directly investigate the role of varying Bcr-Abl expression levels in determining the phenotype and IM sensitivity of hematopoietic cells. CD34(+) cells were transduced with vectors coexpressing Bcr-Abl and GFP, and cells expressing low and high levels of GFP and Bcr-Abl (BA(lo) and BA(hi)) were selected. BA(hi) cells demonstrated enhanced activation of downstream proliferative and antiapoptotic signaling and enhanced proliferation and survival compared to BA(lo) cells. Freshly isolated BA(hi) CD34(+) cells and cell lines demonstrated increased IM-mediated growth inhibition likely reflecting Bcr-Abl dependence for growth and survival. CD34(+) cells expressing BCR/ABL kinase-mutant genes demonstrated resistance to IM-mediated inhibition of proliferation and viability, which was not enhanced by increased expression of BCR/ABL kinase-mutant genes. We conclude that Bcr-Abl overexpression results in increased proliferation and antiapoptotic signaling in CD34(+) cells, but may not play a direct role in IM resistance in progenitor cells expressing either wild-type or mutant BCR/ABL genes. PMID- 17347408 TI - Human platelets synthesize and express functional tissue factor. AB - The source and significance of bloodborne tissue factor (TF) are controversial. TF mRNA, protein, and TF-dependent procoagulant activity (PCA) have been detected in human platelets, but direct evidence of TF synthesis is missing. Nonstimulated monocyte-free platelets from most patients expressed TF mRNA, which was enhanced or induced in all of them after platelet activation. Immunoprecipitation assays revealed TF protein (mainly of a molecular weight [Mr] of approximately 47 kDa, with other bands of approximately 35 and approximately 60 kDa) in nonstimulated platelet membranes, which also increased after activation. This enhancement was concomitant with TF translocation to the plasma membrane, as demonstrated by immunofluorescence-confocal microscopy and biotinylation of membrane proteins. Platelet PCA, assessed by factor Xa (FXa) generation, was induced after activation and was inhibited by 48% and 76% with anti-TF and anti-FVIIa, respectively, but not by intrinsic pathway inhibitors. Platelets incorporated [(35)S]-methionine into TF proteins with Mr of approximately 47 kDa, approximately 35 kDa, and approximately 60 kDa, more intensely after activation. Puromycin but not actinomycin D or DRB (5,6-dichloro-1-beta-D ribofuranosylbenzimidazole) inhibited TF neosynthesis. Thus, human platelets not only assemble the clotting reactions on their membrane, but also supply their own TF for thrombin generation in a timely and spatially circumscribed process. These observations simplify, unify, and provide a more coherent formulation of the current cell-based model of hemostasis. PMID- 17347410 TI - Hypoxic incubation blunts the development of thermogenesis in chicken embryos and hatchlings. AB - We asked to what extent sustained hypoxia during embryonic growth might interfere with the normal development of thermogenesis. White Leghorn chicken eggs were incubated at 38 degrees C either in normoxia (Nx, 21% O2) or in hypoxia [Hx, 15% O2, from embryonic day 5 (E5) until hatching]. The Hx embryos had lower body weight (W) throughout incubation, and hatching was delayed by about 10 h. For both groups, all measurements were conducted in normoxia. At embryonic day E11, the static temperature-oxygen consumption (ambient T-Vo2) curve was typically ectothermic (Q10 = 1.92-1.94) and similar between Nx and Hx. Toward the end of incubation (E20), the Q10 averaged 1.41 +/- 0.06 in Nx and 1.79 +/- 0.08 in Hx (P < 0.005), indicating that the onset of the thermogenic response in Hx lagged behind Nx. In the 1-day-old hatchlings (H1), body weight did not significantly differ between Nx and Hx. At H1, the T-Vo2 curves were endothermic-type, and more so in the older (>8 h old) than in the newly hatched (<8 h old) chicks, whether examined statically or dynamically as a function of time. In either case, the thermogenic responses of Hx were lower than those of Nx. In a 43-31 degrees C thermocline, the preferred T of the Hx hatchlings was around 37.3 degrees C, and similar to Nx, suggesting a similar setpoint for thermoregulation. We conclude that hypoxic incubation blunted the development of thermogenesis. This could be interpreted as an example of epigenetic regulation, in which an environmental perturbation during early development alters the phenotypic expression of a regulatory system. PMID- 17347409 TI - Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones. AB - Three properties define hematopoietic stem cells (HSCs): their capacity for quiescence and long survival, their ability to self-renew, and their ability to give rise to a multilineage clone of differentiating and maturing blood cells. Although it is likely that different signals regulate these events, this has been difficult to dissect on a molecular level, since HSC division, their fate decisions, and the earliest differentiation events cannot be directly visualized. Our studies of c-Mpl, the cellular receptor for the cytokine thrombopoietin, suggest that c-Mpl does not control HSC numbers, as had been previously argued, but rather facilitates the early expansion of differentiating clones. These experiments provide a strategy to distinguish the actions of HSCs from earliest progenitor cells in vivo and demonstrate that a selective growth advantage at a level distal to HSC can result in a profound effect on multilineage hematopoiesis. PMID- 17347411 TI - Functional and molecular characterization of the fluid secretion mechanism in human parotid acinar cells. AB - The strategies available for treating salivary gland hypofunction are limited because relatively little is known about the secretion process in humans. An initial microarray screen detected ion transport proteins generally accepted to be critically involved in salivation. We tested for the activity of some of these proteins, as well as for specific cell properties required to support fluid secretion. The resting membrane potential of human acinar cells was near -51 mV, while the intracellular [Cl-] was approximately 62 mM, about fourfold higher than expected if Cl ions were passively distributed. Active Cl- uptake mechanisms included a bumetanide-sensitive Na+ -K+ -2Cl- cotransporter and paired DIDS sensitive Cl-/HCO3- and EIPA-sensitive Na+/H+ exchangers that correlated with expression of NKCC1, AE2, and NHE1 transcripts, respectively. Intracellular Ca2+ stimulated a niflumic acid-sensitive Cl- current with properties similar to the Ca2+ -gated Cl channel BEST2. In addition, intracellular Ca2+ stimulated a paxilline-sensitive and voltage-dependent, large-conductance K channel and a clotrimazole-sensitive, intermediate-conductance K channel, consistent with the detection of transcripts for KCNMA1 and KCNN4, respectively. Our results demonstrate that the ion transport mechanisms in human parotid glands are equivalent to those in the mouse, confirming that animal models provide valuable systems for testing therapies to prevent salivary gland dysfunction. PMID- 17347413 TI - Botany. A plant receptor with a big family. PMID- 17347412 TI - A G protein-coupled receptor is a plasma membrane receptor for the plant hormone abscisic acid. AB - The plant hormone abscisic acid (ABA) regulates many physiological and developmental processes in plants. The mechanism of ABA perception at the cell surface is not understood. Here, we report that a G protein-coupled receptor genetically and physically interacts with the G protein alpha subunit GPA1 to mediate all known ABA responses in Arabidopsis. Overexpressing this receptor results in an ABA-hypersensitive phenotype. This receptor binds ABA with high affinity at physiological concentration with expected kinetics and stereospecificity. The binding of ABA to the receptor leads to the dissociation of the receptor-GPA1 complex in yeast. Our results demonstrate that this G protein-coupled receptor is a plasma membrane ABA receptor. PMID- 17347414 TI - Direct detection of the asteroidal YORP effect. AB - The Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect is believed to alter the spin states of small bodies in the solar system. However, evidence for the effect has so far been indirect. We report precise optical photometric observations of a small near-Earth asteroid, (54509) 2000 PH5, acquired over 4 years. We found that the asteroid has been continuously increasing its rotation rate omega over this period by domega/dt = 2.0 (+/-0.2) x 10(-4) degrees per day squared. We simulated the asteroid's close Earth approaches from 2001 to 2005, showing that gravitational torques cannot explain the observed spin rate increase. Dynamical simulations suggest that 2000 PH5 may reach a rotation period of approximately 20 seconds toward the end of its expected lifetime. PMID- 17347415 TI - Spin rate of asteroid (54509) 2000 PH5 increasing due to the YORP effect. AB - Radar and optical observations reveal that the continuous increase in the spin rate of near-Earth asteroid (54509) 2000 PH5 can be attributed to the Yarkovsky O'Keefe-Radzievskii-Paddack (YORP) effect, a torque due to sunlight. The change in spin rate is in reasonable agreement with theoretical predictions for the YORP acceleration of a body with the radar-determined size, shape, and spin state of 2000 PH5. The detection of asteroid spin-up supports the YORP effect as an explanation for the anomalous distribution of spin rates for asteroids under 10 kilometers in diameter and as a binary formation mechanism. PMID- 17347416 TI - Environment meets health, again. PMID- 17347417 TI - Nuclear weapons. Livermore Lab dips into the past to win weapons design contest. PMID- 17347418 TI - Wildlife studies. Researchers explore alternatives to elephant culling. PMID- 17347419 TI - Meteorology. A dose of dust that quieted an entire hurricane season? PMID- 17347420 TI - Evolution. Robot suggests how the first land animals got walking. PMID- 17347421 TI - U.S. science policy. Report tells NSF to think more boldly. PMID- 17347422 TI - Research facilities. China supersizes its science. PMID- 17347423 TI - Retrovirus meeting. Hope on new AIDS drugs, but breast-feeding strategy backfires. PMID- 17347424 TI - Evolution. Jurassic genome. PMID- 17347425 TI - Neuroscience. Hunting for meaning after midnight. PMID- 17347426 TI - Did the Olmec know how to write? PMID- 17347427 TI - Hurricanes not the key to a sustainable coast. PMID- 17347428 TI - Climate change CO2 arithmetic. PMID- 17347429 TI - Physics. Watching rush hour in the world of electrons. PMID- 17347430 TI - Biochemistry. A new target for antibiotic development. PMID- 17347431 TI - Cell biology. What a cell should know (but may not). PMID- 17347432 TI - Immunology. Eating in to avoid infection. PMID- 17347433 TI - Applied physics. Oxide electronics emerge. PMID- 17347434 TI - Super plastic bulk metallic glasses at room temperature. AB - In contrast to the poor plasticity that is usually observed in bulk metallic glasses, super plasticity is achieved at room temperature in ZrCuNiAl synthesized through the appropriate choice of its composition by controlling elastic moduli. Microstructures analysis indicates that the super plastic bulk metallic glasses are composed of hard regions surrounded by soft regions, which enable the glasses to undergo true strain of more than 160%. This finding is suggestive of a solution to the problem of brittleness in, and has implications for understanding the deformation mechanism of, metallic glasses. PMID- 17347435 TI - Multifunctional encoded particles for high-throughput biomolecule analysis. AB - High-throughput screening for genetic analysis, combinatorial chemistry, and clinical diagnostics benefits from multiplexing, which allows for the simultaneous assay of several analytes but necessitates an encoding scheme for molecular identification. Current approaches for multiplexed analysis involve complicated or expensive processes for encoding, functionalizing, or decoding active substrates (particles or surfaces) and often yield a very limited number of analyte-specific codes. We present a method based on continuous-flow lithography that combines particle synthesis and encoding and probe incorporation into a single process to generate multifunctional particles bearing over a million unique codes. By using such particles, we demonstrate a multiplexed, single-fluorescence detection of DNA oligomers with encoded particle libraries that can be scanned rapidly in a flow-through microfluidic channel. Furthermore, we demonstrate with high specificity the same multiplexed detection using individual multiprobe particles. PMID- 17347436 TI - Inverse relations between amounts of air pollution and orographic precipitation. AB - Particulate air pollution has been suggested as the cause of the recently observed decreasing trends of 10 to 25% in the ratio between hilly and upwind lowland precipitation, downwind of urban and industrial areas. We quantified the dependence of this ratio of the orographic-precipitation enhancement factor on the amounts of aerosols composed mostly of pollution in the free troposphere, based on measurements at Mt. Hua near Xi'an, in central China. The hilly precipitation can be decreased by 30 to 50% during hazy conditions, with visibility of less than 8 kilometers at the mountaintop. This trend shows the role of air pollution in the loss of significant water resources in hilly areas, which is a major problem in China and many other areas of the world. PMID- 17347437 TI - Structural insight into the transglycosylation step of bacterial cell-wall biosynthesis. AB - Peptidoglycan glycosyltransferases (GTs) catalyze the polymerization step of cell wall biosynthesis, are membrane-bound, and are highly conserved across all bacteria. Long considered the "holy grail" of antibiotic research, they represent an essential and easily accessible drug target for antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus. We have determined the 2.8 angstrom structure of a bifunctional cell-wall cross-linking enzyme, including its transpeptidase and GT domains, both unliganded and complexed with the substrate analog moenomycin. The peptidoglycan GTs adopt a fold distinct from those of other GT classes. The structures give insight into critical features of the catalytic mechanism and key interactions required for enzyme inhibition. PMID- 17347438 TI - Dynamics of replication-independent histone turnover in budding yeast. AB - Chromatin plays roles in processes governed by different time scales. To assay the dynamic behavior of chromatin in living cells, we used genomic tiling arrays to measure histone H3 turnover in G1-arrested Saccharomyces cerevisiae at single nucleosome resolution over 4% of the genome, and at lower (approximately 265 base pair) resolution over the entire genome. We find that nucleosomes at promoters are replaced more rapidly than at coding regions and that replacement rates over coding regions correlate with polymerase density. In addition, rapid histone turnover is found at known chromatin boundary elements. These results suggest that rapid histone turnover serves to functionally separate chromatin domains and prevent spread of histone states. PMID- 17347439 TI - Histone replacement marks the boundaries of cis-regulatory domains. AB - Cellular memory is maintained at homeotic genes by cis-regulatory elements whose mechanism of action is unknown. We have examined chromatin at Drosophila homeotic gene clusters by measuring, at high resolution, levels of histone replacement and nucleosome occupancy. Homeotic gene clusters display conspicuous peaks of histone replacement at boundaries of cis-regulatory domains superimposed over broad regions of low replacement. Peaks of histone replacement closely correspond to nuclease-hypersensitive sites, binding sites for Polycomb and trithorax group proteins, and sites of nucleosome depletion. Our results suggest the existence of a continuous process that disrupts nucleosomes and maintains accessibility of cis regulatory elements. PMID- 17347440 TI - Anaphase onset before complete DNA replication with intact checkpoint responses. AB - Cellular checkpoints prevent mitosis in the presence of stalled replication forks. Whether checkpoints also ensure the completion of DNA replication before mitosis is unknown. Here, we show that in yeast smc5-smc6 mutants, which are related to cohesin and condensin, replication is delayed, most significantly at natural replication-impeding loci like the ribosomal DNA gene cluster. In the absence of Smc5-Smc6, chromosome nondisjunction occurs as a consequence of mitotic entry with unfinished replication despite intact checkpoint responses. Eliminating processes that obstruct replication fork progression restores the temporal uncoupling between replication and segregation in smc5-smc6 mutants. We propose that the completion of replication is not under the surveillance of known checkpoints. PMID- 17347441 TI - From swimming to walking with a salamander robot driven by a spinal cord model. AB - The transition from aquatic to terrestrial locomotion was a key development in vertebrate evolution. We present a spinal cord model and its implementation in an amphibious salamander robot that demonstrates how a primitive neural circuit for swimming can be extended by phylogenetically more recent limb oscillatory centers to explain the ability of salamanders to switch between swimming and walking. The model suggests neural mechanisms for modulation of velocity, direction, and type of gait that are relevant for all tetrapods. It predicts that limb oscillatory centers have lower intrinsic frequencies than body oscillatory centers, and we present biological data supporting this. PMID- 17347442 TI - Ecological speciation in South Atlantic island finches. AB - Examples of sympatric speciation in nature are rare and hotly debated. We describe the parallel speciation of finches on two small islands in the Tristan da Cunha archipelago in the South Atlantic Ocean. Nesospiza buntings are a classic example of a simple adaptive radiation, with two species on each island: an abundant small-billed dietary generalist and a scarce large-billed specialist. Their morphological diversity closely matches the available spectrum of seed sizes, and genetic evidence suggests that they evolved independently on each island. Speciation is complete on the smaller island, where there is a single habitat with strongly bimodal seed size abundance, but is incomplete on the larger island, where a greater diversity of habitats has resulted in three lineages. Our study suggests that the buntings have undergone parallel ecological speciation. PMID- 17347443 TI - Coupling diurnal cytosolic Ca2+ oscillations to the CAS-IP3 pathway in Arabidopsis. AB - Various signaling pathways rely on changes in cytosolic calcium ion concentration ([Ca2+]i). In plants, resting [Ca2+]i oscillates diurnally. We show that in Arabidopsis thaliana, [Ca2+]i oscillations are synchronized to extracellular Ca2+ concentration ([Ca2+]o) oscillations largely through the Ca2+-sensing receptor CAS. CAS regulates concentrations of inositol 1,4,5-trisphosphate (IP3), which in turn directs release of Ca2+ from internal stores. The oscillating amplitudes of [Ca2+]o and [Ca2+]i are controlled by soil Ca2+ concentrations and transpiration rates. The phase and period of oscillations are likely determined by stomatal conductance. Thus, the internal concentration of Ca2+ in plant cells is constantly being actively revised. PMID- 17347444 TI - Odor cues during slow-wave sleep prompt declarative memory consolidation. AB - Sleep facilitates memory consolidation. A widely held model assumes that this is because newly encoded memories undergo covert reactivation during sleep. We cued new memories in humans during sleep by presenting an odor that had been presented as context during prior learning, and so showed that reactivation indeed causes memory consolidation during sleep. Re-exposure to the odor during slow-wave sleep (SWS) improved the retention of hippocampus-dependent declarative memories but not of hippocampus-independent procedural memories. Odor re-exposure was ineffective during rapid eye movement sleep or wakefulness or when the odor had been omitted during prior learning. Concurring with these findings, functional magnetic resonance imaging revealed significant hippocampal activation in response to odor re-exposure during SWS. PMID- 17347445 TI - Measurement of IL-13-induced iNOS-derived gas phase nitric oxide in human bronchial epithelial cells. AB - Exhaled nitric oxide (NO) is altered in numerous diseases including asthma, and is thought broadly to be a noninvasive marker of inflammation. However, the precise source of exhaled NO has yet to be identified, and the interpretation is further hampered by significant inter-subject variation. Using fully differentiated normal human bronchial epithelial (NHBE) cells, we sought to determine (1) the rate of NO release (flux, pl.s(-1.)cm(-2)) into the gas; (2) the effect of IL-13, a prominent mediator of allergic inflammation, on NO release; and (3) inter-subject/donor variability in NO release. NHBE cells from three different donors were cultured at an air-liquid interface and stimulated with different concentrations of IL-13 (0, 1, and 10 ng/ml) for 48 h. Gas phase NO concentrations in the headspace over the cells were measured using a chemiluminescence analyzer. The basal NO flux from the three donors (0.05 +/- 0.03) is similar in magnitude to that estimated from exhaled NO concentrations, and was significantly increased by IL-13 in a donor-specific fashion. The increase in NO release was strongly correlated with inducible nitric oxide synthase (iNOS) gene and protein expression. There was a trend toward enhanced production of nitrate relative to nitrite as an end product of NO metabolism in IL-13-stimulated cells. NO release from airway epithelial cells can be directly measured. The rate of release in response to IL-13 is strongly dependent on the individual donor, but is primarily due to the expression of iNOS. PMID- 17347446 TI - Inhibition of ICMT induces endothelial cell apoptosis through GRP94. AB - Isoprenylcysteine-O-carboxyl methyltransferase (ICMT) catalyzes methylation of proteins containing a C-terminal CAAX motif. We have previously shown that chemical inhibition of ICMT caused endothelial cell apoptosis, an effect correlated with decreased Ras and RhoA carboxyl methylation and GTPase activities. In the current study, proteomic analysis of pulmonary artery endothelial cells (PAEC) exposed to the ICMT inhibitor, N-acetyl-geranylgeranyl cysteine (AGGC), demonstrated a shift in the isoelectric points (pI) of the glucose-regulated protein (GRP) 94. Two-dimensional PAGE and immunoblot analysis further documented that ICMT inhibition caused multiple changes in the pI of GRP94. GRP94 is an endoplasmic reticulum molecular chaperone, a component of the unfolded protein response (UPR), and is involved in apoptosis. Immunofluorescence analyses revealed redistribution and aggregation of GRP94 after 3 h exposure to AGGC. A similar finding was noted with calnexin. In addition, GRP94 protein levels were significantly diminished upon 18 h AGGC exposure or ICMT suppression. The effects of ICMT inhibition on changes in GRP94 subcellular localization and protein content were blunted by overexpression of constitutively active RhoA or a caspase inhibitor. Furthermore, GRP94 depletion augmented endothelial cell apoptosis induced by ICMT inhibition. These results indicate that ICMT inhibition leads to GRP94 relocalization, aggregation, and degradation; effects were dependent upon the activities of RhoA and caspases. We speculate that changes in the pI, subcellular localization, and protein level of GRP94 cause endothelial cell apoptosis, possibly through UPR dysfunction. These studies suggest a novel link between RhoA GTPases and the UPR. PMID- 17347447 TI - No detectable improvements in cystic fibrosis transmembrane conductance regulator by nasal aminoglycosides in patients with cystic fibrosis with stop mutations. AB - Cystic fibrosis (CF) is an autosomal recessive disorder caused by many types of genetic defects, including premature stop codons. Gentamicin can suppress stop mutations in CF transmembrane conductance regulator (CFTR) in vitro and in vivo, leading to improvements in CFTR-dependent ion transport and protein localization to the apical surface of respiratory epithelial cells. The primary objective of this study was to test whether nasally administered gentamicin or tobramycin could suppress premature stop mutations in CFTR, resulting in full-length, functional protein. A secondary objective was to obtain data to aid in the design of multicenter trials using the nasal potential difference as a study endpoint. A multicenter study was conducted in two cohorts of patients with CF, those heterozygous for stop mutations in the CFTR gene and those without nonsense mutations, to investigate the effects of both gentamicin and tobramycin administered over a 28-d period on sequential nasal potential difference and airway cell immunofluorescence endpoints. Eleven patients with CF with stop mutations were enrolled in a randomized, double-blinded, crossover fashion to receive each drug, while 18 subjects with CF without stop mutations were randomized 1:1 in a parallel fashion to receive one drug. After demonstration of drug delivery, neither aminoglycoside produced detectable changes in nasal ion transport or CFTR localization in brushed cells from either study group. These results with first-generation suppressive agents suggest the need for improved drug delivery methods and/or more potent suppressors of nonsense mutations to confer CFTR correction in subjects with CF heterozygous for nonsense mutations. The study provides valuable information on parameters of the nasal potential difference measurements for use in future multicenter clinical trials. PMID- 17347448 TI - Clotrimazole-sensitive K+ currents regulate pacemaker activity in interstitial cells of Cajal. AB - Interstitial cells of Cajal (ICC) are pacemaker cells for gut peristaltic motor activity. Compared with cardiac pacemaker cells, little is known about mechanisms that regulate ICC excitability. The objective of the present study was to investigate a potential role for clotrimazole (CTL)-sensitive K currents (I(CTL)) in the regulation of ICC excitability and pacemaker activity. ICC were studied in situ and in short-term culture by using the whole cell patch-clamp configuration. In situ, ICC exhibited spontaneous transient inward currents followed by transient outward currents. CTL blocked outward currents, thereby increasing the net inward currents, and depolarized ICC, thereby establishing CTL-sensitive channels as regulators of ICC pacemaker activity. In short-term culture, a I(CTL) was identified that showed increased conductance when depolarized from the resting membrane potential to 0 mV and subsequent inward rectification at further depolarized potentials. The I(CTL) markedly increased with increasing intracellular calcium and was insensitive to the ether-a-go-go-related K channel blocker E-4031 and the large-conductance calcium-activated K channel blocker iberiotoxin. I(CTL) contributed 3-9 nS to the whole cell conductance at 0 mV membrane potential under physiological conditions; it was fast activating (tau = 88 ms), showed little time-dependent inactivation, and exhibited a deactivation time constant of 38 ms. The nitric oxide donor sodium nitroprusside (SNP) increased I(CTL). Single-channel activity, activated by calcium and SNP, was inhibited by CTL, with a single-channel conductance of approximately 38 pS. In summary, ICC generate a I(CTL) on depolarization through an intermediate conductance calcium-activated K channel that regulates pacemaker activity and ICC excitability. PMID- 17347449 TI - Local inhibitory reflexes excited by mucosal application of nutrient amino acids in guinea pig jejunum. AB - The motility of the gut depends on the chemicals contained in the lumen, but the stimuli that modify motility and their relationship to enteric neural pathways are unclear. This study examined local inhibitory reflexes activated by various chemical stimulants applied to the mucosa to characterize effective physiological stimuli and the pathways they excite. Segments of the jejunum were dissected to allow access to the circular muscle on one-half of the preparation while leaving the mucosa intact on the circumferentially adjacent half. Chemicals were transiently applied to the mucosa, and responses were recorded intracellularly in nearby circular muscle cells. The amino acids l-phenylalanine, l-alanine, or l tryptophan (all 1 mM) evoked inhibitory junction potentials (IJPs; latency 150 300 ms, amplitude 3-8 mV, each n > 6) that were blocked by TTX and partially blocked by antagonists of P2X receptors and/or a combination of antagonists at 5 HT(3) and 5-HT(4) receptors. The putative mediators 5-HT (10 microM), ATP (1 mM), and CCK-8 (1-10 microM) elicited IJPs mediated via 5-HT(3), P2X, and CCK-B receptors, respectively. Responses were only partially reduced by the effective antagonists. IJPs evoked by electrically stimulating the mucosa were unaffected by antagonists that reduced chemically evoked responses. Both chemically and electrically evoked IJPs were resistant to nicotinic, NK(1), NK(3), alpha-amino-3 hydroxy-5-methylisoxazole-4-propionic acid, N-methyl-d-aspartate, or CGRP receptor blockade. We conclude that mucosal stimulation by amino acids activates local neural pathways whose pharmacology depends on the nature of the stimulus. Transmitters involved at some synapses in these pathways remain to be identified. PMID- 17347450 TI - Portal branch ligation induces a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and cell proliferation in portal blood-deprived liver tissue. AB - Portal branch ligation (PBL) may prevent liver failure after extended hepatic resection. However, clinical studies indicate that tumors within the ligated lobe develop accelerated growth. Although it is well known that tumor growth depends on the host's microvascularization, there is no information about how PBL affects the hepatic microcirculation. Our aims were to determine hepatic artery response, liver microcirculation, tissue oxygenation, and cell proliferation after PBL. Therefore, we used intravital multifluorescence microscopy, laser-Doppler flowmetry, immunohistochemistry, and biochemical techniques to examine microcirculatory responses, microvascular remodeling, and cellular consequences after left lateral PBL in BALB/c mice. During the first 7 days, PBL induced a reduction of left hilar blood flow by approximately 50%. This resulted in 80% sinusoidal perfusion failure, significant parenchymal hypoxia, and liver atrophy. After 14 days, however, left hilar blood flow was found to be restored. However, remodeling of the microvasculature included a rarefaction of the sinusoidal network, however, without substantial perfusion failure, compensated by a hepatic arterial buffer response and significant sinusoidal dilatation. This resulted in normalization of tissue oxygenation, indicating arterialization of the ligated lobe. Interestingly, late microvascular remodeling was associated with increased endothelial nitric oxide synthase expression, significant hepatocellular proliferation, and weight gain of the ligated lobe. Thus PBL induces only an initial microcirculatory failure with liver atrophy, followed by a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and hepatocellular proliferation. This may explain the accelerated tumor progression occasionally observed in patients after PBL. PMID- 17347451 TI - Intestinal epithelial cells from inflammatory bowel disease patients preferentially stimulate CD4+ T cells to proliferate and secrete interferon gamma. AB - Previous studies have suggested that intestinal epithelial cells (IECs) have the capacity to function as nonprofessional antigen presenting cells that in the normal state preferentially activate CD8+ T cells. However, under pathological conditions, such as those found in inflammatory bowel disease (IBD), persistent activation of CD4+ T cells is seen. The aim of this study was to determine whether the IBD IECs contribute to CD4+ T cell activation. Freshly isolated human IECs were obtained from surgical specimens of patients with or without IBD and cocultured with autologous or allogeneic peripheral blood T lymphocytes. Cocultures of normal T cells and IECs derived from IBD patients resulted in the preferential activation of CD4+ T cell proliferation that was associated with significant IFN-gamma, but not IL-2, secretion. Cytokine secretion and CD4+ T cell proliferation was inhibited by pretreatment of the IBD IECs with the anti-DR MAb L243. In contrast, normal IECs stimulated the proliferation and cytokine secretion by CD4+ T cells to a significantly lesser degree than IBD IECs. Furthermore, blockade of human leukocyte antigen-DR had a lesser effect in the normal IEC-CD4+ T cell cocultures. We conclude that IECs can contribute to the ongoing CD4+ T cell activation seen in IBD. We suggest that the apparent differences between the secreted levels of IFN-gamma indicate that it may play a dual role in intestinal homeostasis, in which low levels contribute to physiological inflammation whereas higher levels are associated with an uncontrolled inflammatory state. PMID- 17347452 TI - Ethanol induced NF-{kappa}B activation protects against cell injury in cultured rat gastric mucosal epithelium. AB - Ethanol is a well-established irritant inducing inflammation in gastric mucosa, but the effects at the cellular level remain unclear. This study investigates NF kappaB activation in gastric mucosal cells by ethanol and assesses the effects of heat shock pretreatment in this ulcerogenic situation. Rat gastric mucosal epithelia were exposed to ethanol for different time periods. Heat shock was induced by incubating the cells at 42 degrees C for 1 h prior to the experiments. For evaluation of NF-kappaB activation, the nuclear fraction of the cell lysates was analyzed with an EMSA or an ELISA-based assay. Caspase-3 (a promoter of apoptosis) activity was measured with a time-resolved fluorescence based assay, cell viability with a tetrazolium assay, and cell membrane integrity with a LDH assay. Ethanol (1-5%) induced NF-kappaB activation, reaching a maximum after 3 h, and also led to moderately increased COX-2 expression. Heat shock pretreatment and the intracellular calcium chelator BAPTA were able to inhibit ethanol-induced NF-kappaB activation. Heat shock pretreatment decreased ethanol-induced caspase-3 activation, decreased cell membrane damage, and retained cellular viability. Inhibition of NF-kappaB activation by NEMO-binding peptide, by decreasing RelA expression, or by inhibiting COX-2 activity by CAY-14040 promoted the effects of ethanol, such as increased caspase-3 activity and decreased cell viability. In conclusion, ethanol induces NF-kappaB activation via a calcium-dependent pathway and induces COX-2 expression. Inhibition of the NF-kappaB activation or COX-2 activity potentiates apoptosis and cell damage induced by ethanol, suggesting a protective role for NF-kappaB activation and COX-2 expression. PMID- 17347453 TI - Measurement of liver collagen synthesis by heavy water labeling: effects of profibrotic toxicants and antifibrotic interventions. AB - Enhanced production of collagen is central to fibrotic disorders such as hepatic cirrhosis and pulmonary fibrosis. We describe a sensitive, quantitative, and high throughput technique for measuring hepatic collagen synthesis in vivo through metabolic labeling with heavy water ((2)H(2)O). Rats and mice received (2)H(2)O in drinking water for up to 35 days. Deuterium incorporation into collagen-bound amino acids (AA) alanine and hydroxyproline (OHP) was measured by gas chromatography-mass spectrometry. A threefold stimulation of collagen fractional synthesis was observed under the maximum dosage of carbon tetrachloride (CCl(4); 1.67 ml/kg). Deuterium enrichment was systematically 20% higher in AA from monomeric collagen relative to dimeric collagen, consistent with slower turnover of the latter. Administration of 1% griseofulvin to mice resulted in a significant, threefold increase in liver collagen synthesis, observable within 12 days and consistent with predicted interstrain differences (C57/Bl6J > BALB/c). Deuterium enrichments of OHP from total liver proteins correlated well with alanine or OHP from isolated collagen. Fibrogenesis subsided after withdrawal of CCl(4) exposure and was reduced to various degrees by coadministration of interferon-gamma, rosiglitazone, atorvastatin, or enalapril. Changes in isotopically measured collagen synthesis correlated with, but were more sensitive and reproducible than, standard histological staining (trichrome) for fibrosis. In summary, liver collagen synthesis can be measured sensitively and with high precision over a short time period, without radioactivity, thereby providing a relatively high-throughput in vivo strategy for rapidly measuring profibrotic activities of suspected hepatotoxicants and antifibrotic activities of drug candidates. PMID- 17347454 TI - Corticosteroid receptor-mediated mechanisms in the amygdala regulate anxiety and colonic sensitivity. AB - Our previous studies have shown that stereotaxic implantation of corticosterone (Cort) onto the central amygdaloid nucleus increases both anxiety and colonic sensitivity. The goal of this study was to examine the relative importance of amygdaloid glucocorticoid (GR) and mineralocorticoid receptor (MR)-mediated mechanisms in the induction of anxiety and colonic hypersensitivity. In male Fischer 344 rats, Cort or cholesterol micropellets were stereotaxically implanted bilaterally at the dorsal boundary of the central amygdaloid nucleus either alone or in combination with a GR antagonist, mifepristone, or a MR antagonist, spironolactone. Anxiety was assessed on the elevated plus maze and quantified as the percentage of time spent in open arm exploration. Colonic sensitivity was measured by recording a visceromotor response, the number of abdominal muscle contractions in response to colorectal distension. In Cort-implanted rats there was a significant reduction in the percentage of time spent in the open arms of the elevated plus maze compared with cholesterol controls, indicating increased anxiety. Furthermore, colonic hypersensitivity was observed in response to colorectal distension compared with rats with cholesterol implants. In rats with Cort implants combined with either a GR or MR antagonist, there was a significant inhibition of anxiety and colonic hypersensitivity. Our data suggest that both GR and MR play a critical role in Cort-induced anxiety and colonic hypersensitivity. PMID- 17347455 TI - Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. AB - Diabetic gastroparesis is a disorder that predominantly affects women. However, the biological basis of this sex bias remains completely unknown. In this study we tested the hypothesis that a component of this effect may be mediated by the nitrergic inhibitory system of the enteric nervous system. Age-matched male and female Sprague-Dawley rats were studied 8 or 12 wk after streptozotocin (55 mg/kg body wt ip)-induced sustained hyperglycemia and compared with controls. Solid gastric emptying (GE) studies were performed in all the groups. Changes in gastric antrum neuronal nitric oxide synthase (nNOS) mRNA and protein levels were analyzed by real-time PCR and Western immunoblotting, respectively. nNOS dimerization studies were performed using low-temperature SDS-PAGE. In vitro nitrergic relaxation (area under curve/mg tissue wt) was studied after the application of electric field stimulation in an organ bath. Changes in intragastric pressure (mmHg.s) in freely moving rats in the presence or absence of N(G)-nitro-l-arginine methyl ester (nitric oxide synthase inhibitor) were examined by an ambulatory telemetric method. After diabetes induction, GE is delayed in both male and female rats. However, diabetic females exhibited significant delayed GE than in diabetic males. Compared with male controls, gastric nNOS expression and nitrergic relaxation were substantially elevated in healthy female control rats, accompanied by significantly reduced intragastric pressure. The active dimeric form and dimer-to-monomer ratio of nNOSalpha were also higher in healthy females compared with male rats (P < 0.05). Diabetic females, but not males, showed significant (P < 0.05) impairment in both gastric nNOSalpha dimerization and nitrergic relaxation, accompanied by an increase in intragastric pressure. Our data provide evidence that females may have a greater dependency on the nitrergic mechanisms in health. Furthermore, diabetes seems to affect the nitrergic system to a greater extent in females than in males. Together, these changes may account for the greater vulnerability of females to diabetic gastric dysfunction. PMID- 17347456 TI - Imaging in clinical medicine. Calcified left atrial thrombus. PMID- 17347457 TI - Clinical practice. Pediatric strabismus. PMID- 17347458 TI - Images in clinical medicine. Floating kidneys. PMID- 17347459 TI - Case records of the Massachusetts General Hospital. Case 7-2007. A 59-year-old woman with diabetic renal disease and nonhealing skin ulcers. PMID- 17347461 TI - Ethical challenges posed by the solicitation of deceased and living organ donors. PMID- 17347462 TI - Pioglitazone in nonalcoholic steatohepatitis. PMID- 17347463 TI - Bivalirudin in acute coronary syndromes. PMID- 17347464 TI - Treatment of restenosis with a paclitaxel-coated balloon catheter. PMID- 17347465 TI - The asthma epidemic. PMID- 17347466 TI - Compulsory HPV vaccination. PMID- 17347467 TI - Prolonged bisphosphonate release after treatment in children. PMID- 17347468 TI - Retraction: Guo H. Complication of central venous catheterization. N Engl J Med 2007; 356: e2. PMID- 17347469 TI - The 2005 Thomas Willis Lecture: stroke and vascular cognitive impairment: a transdisciplinary, translational and transactional approach. AB - Advances in stroke are occurring at an unprecedented pace, but often in disciplinary isolation and without optimal mechanisms for systematically translating, integrating and applying the findings. Knowledge accrues in pieces, but is understood in patterns. To optimize knowledge acquisition and application, infrastructures and systems need to be set up along with appealing incentives. The approach needs to be transdisciplinary, going beyond the bounds of any given discipline, reciprocally translational, and transactional, meaning that the interchanges have to yield previously agreed benefits to the parties (The Triple T Approach). A new breed of leaders needs to be developed and nurtured to catalyze the process. Opportunities abound. Stroke and most brain diseases share the same pathophysiological fundamental mechanisms. An integrated, systematic approach to these processes could yield not only greater understanding but new, common therapeutic targets for several diseases. Biphasic clinical trials could combine the best features of pragmatic and explanatory, randomized clinical trials. The greatest opportunity of all may be the largely under-explored and under-exploited borderlands between cerebrovascular and Alzheimer disease. One in three of us will have a stroke, become demented, or both. For each person who has a stroke or Alzheimer disease, two have some cognitive impairment short of dementia, often subclinical cerebrovascular disease on a substrate of Alzheimer changes. The fact that cerebrovascular and Alzheimer disease share the same risk factors, provide a great opportunity for prevention, if implemented at the "brain at risk" stage. Systematically integrating what we know and evaluating what we do could spur progress. Research is not only an activity but an attitude. Making evaluation and incentives to excel part of the funding of all stroke activities would yield far ranging cumulative improvements in all aspects of stroke. No system can replace the individual initiative, creativity and insights that lead to the great discoveries, but progress is not made by breakthroughs alone. No one's work is so exalted that it cannot be improved, nor so humble that it has no value. We can all make a difference. PMID- 17347470 TI - Factors influencing the detection of early CT signs of cerebral ischemia: an internet-based, international multiobserver study. AB - BACKGROUND AND PURPOSE: Early CT signs of cerebral ischemia are subtle. Little is known of which factors influence the detection of infarct signs. We compared neuroradiologists' scan readings with those of other specialists involved in the care of stroke patients. METHODS: We used the Internet to show 63 CT scans, all acquired <6 hours after stroke and representing different patient ages, times to scanning, stroke severity, and early CT signs of ischemia to physicians involved in stroke care. They completed a structured scan interpretation proforma over the Internet. We compared the detection of early ischemic signs stratified by severity and the effect of prior stroke between different specialties. RESULTS: Among 207 observers, neuroradiologists saw significantly more of "any early ischemic changes" than did stroke physicians, general radiologists, geriatricians, or neurologists (all P<0.0001), predominantly due to neuroradiologists' greater detection of "mild" hypoattenuation or swelling. Detection of "severe" hypoattenuation or swelling, and hyperattenuated arteries did not differ between specialties. Old infarcts impaired recognition of early ischemic signs. Non-neuroradiologists did not "over-call" signs. Years of scan reading experience did not account for these differences, but neuroradiologists took, on average, 30 seconds longer to read each scan than did most other specialists (P<0.0001). CONCLUSIONS: Non-neuroradiologists should realize that they are unlikely to over-call signs, that old infarcts may distract them from seeing early ischemic signs, and read stroke CT scans more slowly, as these factors may help them perform more like neuroradiologists. PMID- 17347471 TI - Magnesium for treatment of acute lacunar stroke syndromes: further analysis of the IMAGES trial. AB - BACKGROUND AND PURPOSE: A prespecified interaction analysis of the neutral Intravenous Magnesium Efficacy in Stroke (IMAGES) trial revealed significant benefit from magnesium (Mg) in patients with noncortical stroke. Post hoc analysis indicated that this effect was seen in lacunar clinical syndromes (LACS), interaction P=0.005. We have now examined whether this interaction could be explained by confounding baseline factors. METHODS: LACS was defined on the basis of neurological signs and did not include imaging. We investigated the interaction between baseline variables and Mg treatment on global outcome. We used logistic-regression models to test whether the Mg-LACS interaction remained significant after adjusting for stratification variables, sex, a novel stroke severity score, and baseline variables that had an interaction with treatment (P<0.1). RESULTS: The Mg (n=383) and placebo (n=382) groups of LACS patients were well matched on baseline factors. In addition to LACS, we found an interaction between beneficial Mg treatment effect and younger age (P=0.003), higher baseline diastolic blood pressure (P=0.02), higher mean blood pressure (P=0.02), and absence of ischemic heart disease (P=0.07). Even so, the adjusted Mg-LACS interaction remained significant (odds ratio [OR] 0.57; 95% CI, 0.39 to 0.83; P=0.003). In the LACS subgroup, Mg improved Barthel Index <95 (OR 0.73; 95% CI, 0.55 to 0.98), modified Rankin Scale >1 (OR 0.67; 95% CI, 0.50 to 0.91), and global outcome (OR 0.70; 95% CI, 0.53 to 0.92) but not Barthel Index <60 or mortality. CONCLUSIONS: The positive treatment effect of Mg in LACS cannot be ascribed to general issues of severity, time to treatment, blood pressure, or other baseline factors; equally, this finding may be due to chance. A large trial of Mg treatment in LACS appears justified. PMID- 17347472 TI - Weekends: a dangerous time for having a stroke? AB - BACKGROUND AND PURPOSE: Weekend admissions are associated with higher in-hospital mortality. However, limited information is available concerning the "weekend effect" on stroke mortality. Our aim was to evaluate the impact of weekend admissions on stroke mortality in different settings. METHODS: We analyzed all hospital admissions for ischemic stroke from April 2003 to March 2004 through the Hospital Morbidity Database. The Hospital Morbidity Database is a national database that contains patient-level sociodemographic, diagnostic, procedural, and administrative information including all acute care facilities across Canada. The major inclusion criterion was admission to an acute care facility with a principal diagnosis of ischemic stroke. Clinical variables and facility characteristics were included in the analysis. RESULTS: Overall, 26,676 patients were admitted to 606 hospitals for ischemic stroke. Weekend admissions comprised 6629 (24.8%) of all admissions. Seven-day stroke mortality was 7.6%. Weekend admissions were associated with a higher stroke mortality than weekday admissions (8.5% vs 7.4%; odds ratio, 1.17; 95% CI, 1.06 to 1.29). Mortality was similarly affected among patients admitted to rural versus urban hospitals or when the most responsible physician was a general practitioner versus specialist. In the multivariable analysis, weekend admissions were associated with higher early mortality (odds ratio, 1.14; 95% CI, 1.02 to 1.26) after adjusting for age, sex, comorbidities, and medical complications. CONCLUSIONS: Stroke patients admitted on weekends had a higher risk-adjusted mortality than did patients admitted on weekdays. Disparities in resources, expertise, and healthcare providers working during weekends may explain the observed differences in weekend mortality. PMID- 17347473 TI - Upregulation of macrophage endothelial lipase by toll-like receptors 4 and 3 modulates macrophage interleukin-10 and -12 production. AB - Limited data suggest that endothelial lipase (EL) is synthesized not only by endothelial cells but also by macrophages. Previous studies showed that proinflammatory cytokines upregulate EL in endothelial cells, but there are very few data regarding EL expression, regulation, and functional consequences in macrophages. In the present study, RAW cells and mouse peritoneal macrophages were treated with Toll-like receptor (TLR) ligands and EL expression and its consequences were assessed. We demonstrate that lipopolysaccharide, a TLR4 ligand; and polyinosinic:polycytidylic acid (poly I:C), a TLR3 ligand; but not lipoteichoic acid, a TLR2 ligand, upregulate macrophage EL expression both ex vivo and in vivo. In contrast, macrophage lipoprotein lipase expression is significantly repressed by lipopolysaccharide or poly I:C. Using C3HJ and TLR3 knockout mice, we further show that upregulation of macrophage EL expression by lipopolysaccharide or poly I:C is TLR4 or TLR3 dependent, respectively. Furthermore, we demonstrate that lipopolysaccharide induced interleukin (IL)-10 production was significantly reduced, whereas IL-12 production is significantly increased in J744 macrophages and mouse peritoneal macrophages overexpressing human EL. Conversely, significantly increased IL-10 and significantly decreased IL-12 expression were observed in mouse peritoneal macrophages isolated from EL knockout mice. Finally we show that the catalytic activity is required for EL to modulate the balance of macrophage IL-10 and IL-12 production. These results suggest that macrophage EL may play important roles in modulating the macrophage inflammatory response through local hydrolysis of HDL. PMID- 17347474 TI - Transient exposure to hydrogen peroxide causes an increase in mitochondria derived superoxide as a result of sustained alteration in L-type Ca2+ channel function in the absence of apoptosis in ventricular myocytes. AB - We sought to understand the effect of a transient exposure of cardiac myocytes to H(2)O(2) at a concentration that did not induce apoptosis. Myocytes were exposed to 30 micromol/L H(2)O(2) for 5 minutes followed by 10 U/mL catalase for 5 minutes to degrade the H(2)O(2). Cellular superoxide was measured using dihydroethidium. Transient exposure to H(2)O(2) caused a 66.4% increase in dihydroethidium signal compared with controls exposed to only catalase, without activation of caspase 3 or evidence of necrosis. The increase in dihydroethidium signal was attenuated by the mitochondrial inhibitors myxothiazol or carbonyl cyanide p-(trifluoromethoxy)phenyl-hydrazone and when calcium uptake by the mitochondria was inhibited with Ru360. We investigated the L-type Ca(2+) channel (I(Ca-L)) as a source of calcium influx. Nisoldipine, an inhibitor of I(Ca-L), attenuated the increase in superoxide. Basal channel activity increased from 5.4 to 8.9 pA/pF. Diastolic calcium was significantly increased in quiescent and contracting myocytes after H(2)O(2). The response of I(Ca-L) to beta-adrenergic receptor stimulation was used as a functional reporter because decreasing intracellular H(2)O(2) alters the sensitivity of I(Ca-L) to isoproterenol. H(2)O(2) increased the K(0.5) required for activation of I(Ca-L) by isoproterenol from 5.8 to 27.8 nmol/L. This effect and the increase in basal current density persisted for several hours after H(2)O(2). We propose that extracellular H(2)O(2) is associated with an increase in superoxide from the mitochondria caused by an increase in Ca(2+) influx from I(Ca-L). The effect persists because a positive feedback exists among increased basal channel activity, elevated intracellular calcium, and superoxide production by the mitochondria. PMID- 17347475 TI - Myozenin 2 is a novel gene for human hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in sarcomeric proteins (excluding phenocopy). The causal genes in approximately one third of the cases remain unknown. We identified a family comprised of 6 clinically affected members. The phenotype was characterized by early onset of symptoms, pronounced cardiac hypertrophy, and cardiac arrhythmias. We excluded MYH7, MYBPC3, TNNT2, and ACTC1 as the causal gene either by direct sequencing or by haplotype analysis. To map the putative candidate sarcomeric gene, we perforbold locus-specific haplotyping to detect cosegregation of the locus haplotype with the phenotype, followed by mutation screening. We genotyped 5 short-tandem-repeat markers that spanned a 4.4-centimorgan region on 4q26-q27 locus and encompassed myozenin 2 (MYOZ2), a Z-disk protein. The maximum logarithm of odds score was 2.03 (P=0.005). All affected members shared a common haplotype, implicating MYOZ2 as the causal gene. To detect the causal mutation, we sequenced all exons and exon-intron boundaries of MYOZ2 in 10 family members and identified a T-->C missense mutation corresponding to S48P substitution, which cosegregated with inheritance of HCM (N=6). It was absent in 4 clinically normal family members and in 658 additional normal individuals. To determine frequency of the MYOZ2 mutations in HCM, we sequenced MYOZ2 in 516 HCM probands and detected another missense mutation (I246M). It was absent in 2 normal family members and 517 controls. Both mutations affect highly conserved amino acids. We conclude MYOZ2 is a novel causal gene for human HCM. PMID- 17347476 TI - Trabeculated right ventricular free wall in the chicken heart forms by ventricularization of the myocardium initially forming the outflow tract. AB - Recent molecular lineage analyses in mouse have demonstrated that the right ventricle is recruited from anterior mesoderm in later stages of cardiac development. This is in contrast to current views of development in the chicken heart, which suggest that the initial heart tube contains a subset of right ventricular precursors. We investigated the fate of the outflow tract myocardium using immunofluorescent staining of the myocardium, and lineage tracer, as well as cell death experiments. These analyses showed that the outflow tract is initially myocardial in its entirety, increasing in length up to HH24. The outflow tract myocardium, subsequently, shortens as a result of ventricularization, contributing to the trabeculated free wall, as well as the infundibulum, of the right ventricle. During this shortening, the overall length of the outflow tract is maintained because of the formation of a nonmyocardial portion between the distal myocardial border and the pericardial reflections. Cell death and transdifferentiation were found to play a more limited contribution to the initial shortening than is generally appreciated, if they play any part at all. Cell death, nonetheless, plays an important role in the disappearance of the myocardial collar that continues to invest the aorta and pulmonary trunk around HH30, and in the separation of the intrapericardial arterial vessels. Taken together, we show, as opposed to some current beliefs, the development of the arterial pole is similar in mammals and birds. PMID- 17347477 TI - Interaction between Na+/K+-pump and Na+/Ca2+-exchanger modulates intercellular communication. AB - Ouabain, a specific inhibitor of the Na(+)/K(+)-pump, has previously been shown to interfere with intercellular communication. Here we test the hypothesis that the communication between vascular smooth muscle cells is regulated through an interaction between the Na(+)/K(+)-pump and the Na(+)/Ca(2+)-exchanger leading to an increase in the intracellular calcium concentration ([Ca(2+)](i)) in discrete areas near the plasma membrane. [Ca(2+)](i) in smooth muscle cells was imaged in cultured rat aortic smooth muscle cell pairs (A7r5) and in rat mesenteric small artery segments simultaneously with force. In A7r5 coupling between cells was estimated by measuring membrane capacitance. Smooth muscle cells were uncoupled when the Na(+)/K(+)-pump was inhibited either by a low concentration of ouabain, which also caused a localized increase of [Ca(2+)](i) near the membrane, or by ATP depletion. Reduction of Na(+)/K(+)-pump activity by removal of extracellular potassium ([K(+)](o)) also uncoupled cells, but only after inhibition of K(ATP) channels. Inhibition of the Na(+)/Ca(2+)-exchange activity by SEA0400 or by a reduction of the equilibrium potential (making it more negative) also uncoupled the cells. Depletion of intracellular Na(+) and clamping of [Ca(2+)](i) at low concentrations prevented the uncoupling. The experiments suggest that the Na(+)/K(+)-pump may affect gap junction conductivity via localized changes in [Ca(2+)](i) through modulation of Na(+)/Ca(2+)-exchanger activity. PMID- 17347478 TI - Early exercise training normalizes myofilament function and attenuates left ventricular pump dysfunction in mice with a large myocardial infarction. AB - The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca(2+)-handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on left ventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LV dimensions, but improved LV fractional shortening from 8+/-1 to 12+/-1%, and LVdP/dt(P30) from 5295+/-207 to 5794+/-207 mm Hg/s (both P<0.05), and reduced pulmonary congestion. These global effects of exercise were associated with normalization of the MI-induced increase in myofilament Ca(2+)-sensitivity (DeltapCa(50)=0.037). This effect of exercise was PKA-mediated and likely because of improved beta(1)-adrenergic signaling, as suggested by the increased beta(1) adrenoceptor protein (48%) and cAMP levels (36%; all P<0.05). Exercise prevented the MI-induced decreased maximum force generating capacity of skinned cardiomyocytes (F(max) increased from 14.3+/-0.7 to 18.3+/-0.8 kN/m(2) P<0.05), which was associated with enhanced shortening of unloaded intact cardiomyocytes (from 4.1+/-0.3 to 7.0+/-0.6%; P<0.05). Furthermore, exercise reduced diastolic Ca(2+)-concentrations (by approximately 30%, P<0.05) despite the unchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect on Ca(2+)-transient amplitude, indicating that the improved LV and cardiomyocyte shortening were principally because of improved myofilament function. In conclusion, early exercise in mice after a large MI has no effect on LV remodeling, but attenuates global LV dysfunction. The latter can be explained by the exercise-induced improvement of myofilament function. PMID- 17347479 TI - Intimal smooth muscle cells of porcine and human coronary artery express S100A4, a marker of the rhomboid phenotype in vitro. AB - We reported that smooth muscle cell (SMC) populations isolated from normal porcine coronary artery media exhibit distinct phenotypes: spindle-shaped (S) and rhomboid (R). R-SMCs are recovered in higher proportion from stent-induced intimal thickening compared with media suggesting that they participate in intimal thickening formation. Our aim was to identify a marker of R-SMCs in vitro and to explore its possible expression in vivo. S- and R-SMC protein extracts were compared by means of 2-dimensional polyacrylamide gel electrophoresis followed by tandem mass spectrometry. S100A4 was found to be predominantly expressed in R-SMC extracts. Using a monoclonal S100A4 antibody we confirmed that S100A4 is highly expressed by R-SMCs and hardly detectable in S-SMCs. S100A4 was colocalized with alpha-smooth muscle actin in stress fibers of several quiescent cells and upregulated during migration. PDGF-BB, FGF-2 or coculture with endothelial cells, which modulate S-SMCs to a R-phenotype, increased S100A4 expression in both S- and R-SMCs. Silencing of S100A4 mRNA in R-SMCs decreased cell proliferation, suggesting a functional role for this protein. In vivo S100A4 was absent in normal porcine coronary artery media, but highly expressed by SMCs of stent-induced intimal thickening. In humans, S100A4 was barely detectable in coronary artery media and markedly expressed in SMCs of atheromatous and restenotic coronary artery lesions. Our results indicate that S100A4 is a marker of porcine R-SMCs in vitro and of intimal SMCs during intimal thickening development. It is also a marker of a large population of human atheromatous and restenotic SMCs. Clarifying S100A4 function might be useful to understand the evolution of atherosclerotic and restenotic processes. PMID- 17347480 TI - Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. AB - We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosolic calcium was determined fluorometrically in 3T3-L1-preadipocytes and in human visceral fat tissue. Adipogenesis in stimulated 3T3-L1-preadipocytes was determined by oil red O-staining of intracellular lipid droplets, triglyceride levels, expression of peroxisome proliferator-activated receptor-gamma, and expression of fatty acid synthase. Long-term feeding experiments were undertaken in wild-type mice and TRPV1 knockout mice. We detected TRPV1 channels in 3T3-L1 preadipocytes and visceral adipose tissue from mice and humans. In vitro, the TRPV1 agonist capsaicin dose-dependently induced calcium influx and prevented the adipogenesis in stimulated 3T3-L1-preadipocytes. RNA interference knockdown of TRPV1 in 3T3-L1-preadipocytes attenuated capsaicin-induced calcium influx, and adipogenesis in stimulated 3T3-L1-preadipocytes was no longer prevented. During regular adipogenesis TRPV1 channels were downregulated which was accompanied by a significant and time-dependent reduction of calcium influx. Compared with lean counterparts in visceral adipose tissue from obese db/db and ob/ob mice, and from obese human male subjects we observed a reduced TRVP1 expression. The reduced TRPV1 expression in visceral adipose tissue from obese humans was accompanied by reduced capsaicin-induced calcium influx. The oral administration of capsaicin for 120 days prevented obesity in male wild type mice but not in TRPV1 knockout mice assigned to high fat diet. We conclude that the activation of TRPV1 channels by capsaicin prevented adipogenesis and obesity. PMID- 17347481 TI - Retrospective analysis of coagulation factor II receptor (F2R) sequence variation and coronary heart disease in hypertensive patients. AB - OBJECTIVES: The purpose of this study was to evaluate the role of genetic variants within the coagulation factor II receptor (F2R) in the occurrence of coronary heart disease (CHD). METHODS AND RESULTS: Four SNPs (-1738 G/A, 2860 G/A, 2930 T/C, and 9113 C/A) and an ins/del polymorphism -506-/GGCCGCGGGAAGC (D/I), replicating a consensus sequence for Ets-1 transcription factor, and their related haplotypes were tested for association to CHD in 1600 hypertensive patients divided in 2 groups according to presence (cases, n=559) and absence (controls, n=1041) of CHD. Allele I at -506 locus was associated with increased risk of CHD under additive, dominant, and recessive models of inheritance (all P<0.01). Three haplotypes carrying I allele were consistently associated with an increased risk of CHD (all P<0.05). Patients homozygous for the C allele at the 2930 locus also showed an increased risk of CHD (P<0.05). To test the functionality of -506 locus, nuclear extracts were incubated with -506D and -506I sequences by EMSA and F2R promoter activity (F2R-A) were assessed in HUVECs transfected with vectors carrying -506D and -506I sequences and exposed to hypoxia. Presence of the -506I sequence was associated with a 26% reduction of affinity binding to nuclear proteins and to blunted F2R-A in response to hypoxia as compared with the -506D sequence (all P<0.05). CONCLUSIONS: F2R genetic variants may influence the natural history of CHD in patients at high risk of cardiovascular events. PMID- 17347482 TI - Inhibition of the renin-angiotensin system abolishes the proatherogenic effect of uremia in apolipoprotein E-deficient mice. AB - OBJECTIVE: Uremia accelerates atherosclerosis in apolipoprotein E-deficient (apoE /-) mice. We examined whether this effect may be preventable by pharmacological blockade of the renin-angiotensin system (RAS). METHODS AND RESULTS: Uremia was induced in apoE-/- mice by 5/6 nephrectomy (NX). Treatment with the angiotensin converting enzyme inhibitor enalapril (2 or 12 mg/kg/d) from week 4 to 36 after NX reduced the aortic plaque area fraction from 0.23+/-0.02 (n=20) in untreated mice to 0.11+/-0.01 (n=21) and 0.08+/-0.01 (n=23), respectively (P<0.0001); the aortic plaque area fraction was 0.09+/-0.01 (n=22) in sham-operated controls. Enalapril from week 20 to 44 after NX also retarded the progression of atherosclerosis. Plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) and concentrations of IgM antibodies against oxidized low density lipoprotein (OxLDL) increased after NX (P<0.01). Enalapril (12 mg/kg/d) attenuated these increases (P<0.05) and reduced aortic expression of vascular cell adhesion molecule (VCAM)-1 mRNA (P<0.05). Atherosclerosis in NX mice was also reduced by losartan (an angiotensin II receptor-blocker), but not when blood pressure was lowered with hydralazine (a non-RAS-dependent vasodilator). CONCLUSION: The results suggest that inhibition of RAS abolishes the proatherogenic effect of uremia independent of its blood pressure-lowering effect, possibly because of antiinflammatory and antioxidative mechanisms. PMID- 17347483 TI - EXP3179 inhibits collagen-dependent platelet activation via glycoprotein receptor VI independent of AT1-receptor antagonism: potential impact on atherothrombosis. AB - OBJECTIVE: Thrombus formation after atherosclerotic plaque rupture critically involves the platelet collagen receptor glycoprotein (GP) VI. We investigated the impact of EXP3179, an active metabolite of the angiotensin II type 1 (AT1) receptor antagonist Losartan (LOS) on GPVI-dependent platelet activation. METHODS AND RESULTS: EXP3179 and LOS but not EXP3174--the major AT1-receptor blocking metabolite of LOS--dose-dependently inhibited collagen-I (P<0.01) and GPVI dependent platelet aggregation (P<0.01) analyzed by optical aggregometry. Platelet activation was further determined by flow cytometry measuring the expression of platelet PAC-1, an epitope of the activated fibrinogen-receptor complex. EXP3179 and LOS inhibited collagen-I (P<0.01) and GPVI-dependent PAC-1 expression (P<0.01). EXP3179 and LOS but not EXP3174 decreased the adhesion of GPVI-receptor expressing Chinese hamster ovarian cells on collagen-I under arterial shear conditions determined by flow chamber analysis (P<0.01 and P<0.05). EXP3179 also reduced human atherosclerotic plaque material-induced platelet aggregation (P<0.01) in vitro and murine platelet adhesion after acute vessel injury in vivo as determined by intravital microscopy (P<0.01). CONCLUSION: EXP3179 acts as a specific inhibitor of the platelet collagen receptor GPVI independent of AT1-receptor antagonism. Further investigations may clarify its individual potential as a novel pharmacological approach to specifically inhibit atherothrombotic events by GPVI-receptor blockade. PMID- 17347484 TI - HDL oxidation compromises its influence on paraoxonase-1 secretion and its capacity to modulate enzyme activity. AB - OBJECTIVE: The purpose of this study was to analyze the consequences of HDL oxidation for paraoxonase-1 metabolism and function. METHODS AND RESULTS: HDL was oxidized with AAPH, copper ions, and hypochlorite. Secretion studies were performed using human paraoxonase-1-transfected cells lines and primary rat hepatocytes. Stability studies were performed with recombinant paraoxonase. Conditioned medium had significantly reduced paraoxonase-1 when Cu or AAPH oxidized HDL was the acceptor complex (P<0.01); reduction was dose-dependent on the degree of oxidation. Oxidized HDL had a reduced capacity to stabilize/improve activity of secreted paraoxonase-1. Reduced secretion could not be attributed to enzyme inactivation by lipoperoxides, reduced binding affinity of HDL, or oxidation of the lipid component alone. Hypochlorite oxidation of HDL did not modify HDL-mediated paraoxonase-1 release, but activity of HDL-associated paraoxonase-1 was particularly sensitive to such treatment. CONCLUSIONS: AAPH and copper, but not hypochlorite, oxidation of HDL compromises its ability to promote release of paraoxonase-1 and stabilize enzyme activity. HDL-associated paraoxonase-1 is highly sensitive to hypochlorite. Reducing paraoxonase-1 renders HDL susceptible to oxidation, which may compromise HDL function. It provides a novel example at the HDL level of the detrimental effects of oxidative stress, and underlines the need for further evaluation of the consequences of HDL oxidation. PMID- 17347485 TI - Darbepoetin-alpha does not promote microvascular thrombus formation in mice: role of eNOS-dependent protection through platelet and endothelial cell deactivation. AB - OBJECTIVE: Erythropoietin (EPO) treatment has become the standard treatment of renal anemia. Though a link between hematopoiesis-stimulating drugs and thrombosis has not been proven, it is generally assumed that systemic application of EPO and its analogues increases the risk for thrombotic events. METHODS AND RESULTS: Here we show in C57BL/6J mice that 4-week treatment with the long lasting EPO analogue darbepoetin-alpha (DPO) at a dose of 10 microg/kg/week induces a reduction of platelet reactivity using flow cytometry and Western blot analysis of tyrosine-specific platelet phosphorylation. Additionally, immunohistochemistry of endothelial adhesion molecule expression and ELISA of circulating endothelial activation markers demonstrated a reduced endothelial activation. Immunohistochemistry and RT-PCR analysis revealed a significant (P<0.05) increase of eNOS expression. Further, DPO did not exert prothrombogenic effects in a murine intravital microscopic thrombosis model of the cremaster muscle. The role of eNOS in prevention of DPO-mediated microvascular thrombosis is further underlined by a significantly accelerated thrombus formation on DPO treatment in eNOS (-/-) mice. CONCLUSION: Thus, DPO-related erythropoiesis with a raised hematocrit is not associated with an increased risk for thrombosis as long as endothelial NO production serves as compensatory mechanism. PMID- 17347486 TI - Dysregulated bone morphogenetic protein signaling in monocrotaline-induced pulmonary arterial hypertension. AB - BACKGROUND: Mutations in the bmpr2 gene, encoding the type II bone morphogenetic protein (BMP) receptor, have been identified in patients with pulmonary arterial hypertension (PAH), implicating BMP signaling in PAH. The aim of this study was to assess BMP signaling and its physiological effects in a monocrotaline (MCT) model of PAH. METHODS AND RESULTS: Expression of BMP receptors Ib and II, and Smads 4, 5, 6, and 8, was downregulated in lungs but not kidneys of MCT-treated rats. Smad1 phosphorylation and expression of BMP/Smad target genes id1 and id3 was also reduced, although ERK1/2 and p38(MAPK) phosphorylation remained unaffected. BMP receptor and Smad expression, Smad1 phosphorylation, and induction of the BMP/Smad-responsive element of the id1 promoter were reduced in pulmonary artery smooth muscle cells (PASMCs) from MCT-treated rats. As a consequence of impaired BMP/Smad signaling, PASMCs from MCT-treated rats were resistant to apoptosis induced by BMP-4 and BMP-7, and were also resistant to BMP 4 antagonism of proliferation induced by platelet-derived growth factor. CONCLUSION: BMP signaling and BMP-regulated physiological phenomena are perturbed in MCT-treated rats, lending solid support to the proposed roles for BMP signaling in the pathogenesis of human PAH. PMID- 17347487 TI - cAMP signaling in leukocyte transendothelial migration. AB - The migration of leukocytes across the vascular endothelium is crucial for immunosurveillance as well as for inflammatory responses. Uncontrolled leukocyte transendothelial migration results in pathologies such as asthma, rheumatoid arthritis, and atherosclerosis. The molecular mechanisms that regulate leukocyte transendothelial migration involve signaling downstream of intracellular messengers such as cAMP, calcium, phosphoinositol lipids, or reactive oxygen species. Among these, cAMP is particularly intriguing because it is generated in both leukocytes and endothelial cells and regulates leukocyte chemotaxis as well as endothelial barrier function. In addition, physiological stimuli that induce cAMP production generate both pro- and antiinflammatory signals, underscoring the complexity of cAMP-driven signaling. This review discusses our current knowledge of the control of leukocyte transendothelial migration by two main cAMP effectors: protein kinase A and the Rap exchange factor Epac (Exchange protein directly activated by cAMP). PMID- 17347490 TI - In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas. AB - Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single modality treatments, the combination of AN-9 and radiation significantly inhibited tumor growth and prolonged time to failure in mice bearing glioma xenografts. The enhanced response to radiation was accompanied by inhibition of cellular proliferation and by increased phosphorylation of H2AX, implicating DNA double-strand breaks in the antineoplastic effects of AN-9 and radiation. The data suggest that AN-9 in combination with radiation may be an effective therapy for malignant gliomas. PMID- 17347491 TI - Temozolomide in children with progressive low-grade glioma. AB - We conducted a phase II study to assess the efficacy of oral temozolomide (TMZ) in children with progressive low-grade glioma. Thirty eligible patients were enrolled on this study. Median age at enrollment was 10 years (range, 4-18 years). Eligible patients received TMZ (200 mg/m(2) per day) by mouth for five days every four weeks. Patients received a median of nine cycles (range, 2-12 cycles) of treatment. Best responses in the 26 patients (86%) with optic pathway glioma (OPG)/pilocytic astrocytoma (PA) included partial response in 3 patients (11%), minor response in 1 (4%), stable disease in 10 (38%), and progressive disease in 12 (46%). Only one of four patients with fibrillary astrocytoma had stable disease for 29 months after TMZ. The overall disease stabilization rate in patients with OPG/PA was 54%, and disease control was maintained for a median interval of 34 months. Seventeen of 26 patients had progressive disease either on or off therapy, and three have died of disease. The two-year progression-free and overall survivals in patients with OPG/PA were 49% (95% CI, 30%-67%) and 96% (95% CI, 89%-100%), respectively. Worst toxicity related to TMZ in all 30 patients included grade 2-4 thrombocytopenia in seven patients, grade 2-4 neutropenia in seven, grade 2 skin rash in one, and intratumor hemorrhage in one. TMZ given in this schedule was successful in stabilizing disease in a significant proportion of the patients with OPG/PA, with manageable toxicity. PMID- 17347492 TI - Induction of senile osteoporosis in normal mice by intra-bone marrow-bone marrow transplantation from osteoporosis-prone mice. AB - A P6 substrain of the senescence accelerated mouse (SAMP6) spontaneously develops osteoporosis early in life. These mice show the clinical signs of osteoporosis, such as elevated levels of urinary deoxypyridinoline (Dpd), decreased bone mineral density (BMD), and a significant loss of trabecular and cortical bone thickness at 12 months of age. Here, we describe the transfer of osteoporosis to a normal strain by the injection of bone marrow cells from SAMP6 donors directly into the bone marrow cavity (intra-bone marrow-bone marrow transplantation [IBM BMT]). More than 1 month after IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived cells, and bone marrow stromal cells that could differentiate into osteocytes were also found to be of donor origin. In addition, the recipient C57BL/6 mouse showed the features of osteoporosis in the trabecular bone. Decreases in BMD and increases in urinary Dpd were also observed. When the message levels of cytokines (interleukin [IL]-11, IL-6, receptor activator of NF kappaB ligand [RANKL], osteoprotegerin, macrophage-colony-stimulating factor, and insulin-like growth factor-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR analysis, IL-6 and IL-11 were reduced to a level similar to that in SAMP6 mice, whereas that of RANKL was increased. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment are reconstituted as a result of IBM-BMT, and suggest that the development of senile osteoporosis might be attributable to "stem cell disorders." Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17347493 TI - Granulocyte colony-stimulating factor prior to nonmyeloablative irradiation decreases murine host hematopoietic stem cell function and increases engraftment of donor marrow cells. AB - The use of nonmyeloablative conditioning prior to bone marrow transplantation is an important component of transplantation-based therapies for nonmalignant blood diseases. In this study, treatment of recipient mice with granulocyte colony stimulating factor (G-CSF) prior to low-dose total body irradiation (LD-TBI) enhanced long-term engraftment of freshly isolated congenic marrow 1.5- to 2-fold more than treatment with LD-TBI alone. This combined regimen was also evaluated in a mouse model of X-linked chronic granulomatous disease (X-CGD), where neutrophils have a defective NADPH oxidase due to genetic deletion of the gp91(phox) subunit. Long-term engraftment of male X-CGD bone marrow cells cultured ex vivo for retroviral transduction of gp91(phox) was enhanced by approximately 40% when female X-CGD recipients were pretreated with G-CSF prior to 300 cGy. These data confirm that sequential treatment with G-CSF and LD-TBI prior to transplantation increases long-term engraftment of donor marrow, and they extend this approach to transplantation of murine donor marrow cultured ex vivo for gene transfer. Additional studies showed that the administration of G CSF prior to LD-TBI did not alter early homing of donor marrow cells. However, the combined regimen significantly decreased the content of long-term repopulating cells in recipient marrow compared with LD-TBI alone, as assessed in competitive assays, which may contribute to the enhanced engraftment of donor marrow cells. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17347494 TI - Commentary: isolated stem cells--patentable as cultural artifacts? AB - This article argues that an isolated embryonic stem cell basically represents a cultural artifact that has no equivalent to cells of the embryo, and that it is likely that the isolation of adult stem cells has a similar consequence. An isolated stem cell could thus be distinguished as something other than the stem cell existing as part of a human body. Since isolation of stem cells implies modification, product patents should, where the results carry enough novelty, inventive step, and potential for industrial application, as a matter of principle be a viable option for patent authorities. Questions of morality, which may affect the patentability, should also be viewed in light of the distinction between isolated result and body part. At the same time, it is essential that patent authorities do not accept broad patent claims that will be detrimental to research. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17347495 TI - Tissue transglutaminase is essential for integrin-mediated survival of bone marrow-derived mesenchymal stem cells. AB - Autologous mesenchymal stem cell (MSC) transplantation therapy for repair of myocardial injury has inherent limitations due to the poor viability of the stem cells after cell transplantation. Adhesion is a prerequisite for cell survival and also a key factor for the differentiation of MSCs. As a novel prosurvival modification strategy, we genetically engineered MSCs to overexpress tissue transglutaminase (tTG), with intention to enhance adhesion and ultimately cell survival after implantation. tTG-transfected MSCs (tTG-MSCs) showed a 2.7-fold and greater than a twofold increase of tTG expression and surface tTG activity, respectively, leading to a 20% increased adhesion of MSCs on fibronectin (Fn). Spreading and migration of tTG-MSCs were increased 4.75% and 2.52%, respectively. Adhesion of tTG-MSCs on cardiogel, a cardiac fibroblast-derived three-dimensional matrix, showed a 33.1% increase. Downregulation of tTG by transfection of small interfering RNA specific to the tTG resulted in markedly decreased adhesion and spread of MSCs on Fn or cardiogel. tTG-MSCs on Fn significantly increased phosphorylation of focal adhesion related kinases FAK, Src, and PI3K. tTG-MSCs showed significant retention in infarcted myocardium by forming a focal adhesion complex and developed into cardiac myocyte-like cells by the expression of cardiac-specific proteins. Transplantation of 1 x 10(6) MSCs transduced with tTG into the ischemic rat myocardium restored normalized systolic and diastolic cardiac function. tTG-MSCs further restored cardiac function of infarcted myocardium as compared with MSC transplantation alone. These findings suggested that tTG may play an important role in integrin-mediated adhesion of MSCs in implanted tissues. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17347496 TI - Course of FEV(1) after onset of bronchiolitis obliterans syndrome in lung transplant recipients. AB - RATIONALE: Bronchiolitis obliterans syndrome (BOS), defined by loss of lung function, develops in the majority of lung transplant recipients. However, there is a paucity of information on the subsequent course of lung function in these patients. OBJECTIVES: To characterize the course of FEV(1) over time after development of BOS and to determine the predictors that influence the rate of functional decline of FEV(1). METHODS: FEV(1)% predicted (FEV(1)%pred) trajectories were studied in 111 lung transplant recipients with BOS by multivariate, linear, mixed-effects statistical models. MEASUREMENTS AND MAIN RESULTS: FEV(1)%pred varied over time after BOS onset, with the steepest decline typically seen in the first 6 months (12% decline; p < 0.0001). Bilateral lung transplant recipients had significantly higher FEV(1)%pred at BOS diagnosis (71 vs. 47%; p < 0.0001) and at 24 months after BOS onset (58 vs. 41%; p = 0.0001). Female gender and pretransplant diagnosis of idiopathic pulmonary fibrosis were associated with a steeper decline in FEV(1)%pred in the first 6 months after BOS diagnosis (p = 0.02 and 0.04, respectively). A fall in FEV(1) greater than 20% in the 6 months preceding BOS (termed "rapid onset") was associated with shorter time to BOS onset (p = 0.01), lower FEV(1)%pred at BOS onset (p < 0.0001), steeper decline in the first 6 months (p = 0.03), and lower FEV(1)%pred at 2 years after onset (p = 0.0002). CONCLUSIONS: Rapid onset of BOS, female gender, pretransplant diagnosis of idiopathic pulmonary fibrosis, and single-lung transplantation are associated with worse pulmonary function after BOS onset. PMID- 17347497 TI - Calcium channel blocker prevents T helper type 2 cell-mediated airway inflammation. AB - RATIONALE: Ca(2+) signaling controls the production of T helper (Th) type 2 cytokines known to be deleterious in asthma. Recently, we showed that Ca(2+) signaling was dihydropyridine (DHP)-sensitive in Th2 lymphocytes and that the DHP derivate, nicardipine, used in the treatment of cardiovascular pathologies, prevents Th2-dependent B cell polyclonal activation. OBJECTIVES: We tested the effect of nicardipine in experimental allergic asthma. METHODS: BALB/c mice immunized with ovalbumin (OVA) in alum and challenged with intranasal OVA were treated with nicardipine once the Th2 response, or even airway inflammation, was induced. We also tested the effect of nicardipine in asthma induced by transferring OVA-specific Th2 cells in BALB/c mice exposed to intranasal OVA. We checked the impact of nicardipine on T-cell responses and airway inflammation. MEASUREMENTS AND MAIN RESULTS: Nicardipine inhibited in vitro Ca(2+) response in Th2 cells. In vivo, it impeded the development of Th2-mediated airway inflammation and reduced the capacity of lymphocytes from lung-draining lymph nodes to secrete Th2, but not Th1, cytokines. Nicardipine did not affect antigen presentation to CD4(+) T lymphocytes, nor the initial localization of Th2 cells into the lungs of mice exposed to intranasal OVA; however, it reduced the production of type 2 cytokines and the amplification of the Th2 response in mice with asthma. Conversely, nicardipine had no effect on Th1-mediated airway inflammation. CONCLUSIONS: Nicardipine improves experimental asthma by impairing Th2-dependent inflammation. This study could provide a rationale for developing drugs selectively targeting DHP receptors of Th2 lymphocytes, potentially beneficial in the treatment of asthma. PMID- 17347499 TI - AIDS and palliative care in South Africa. AB - As a result of limited access to antiretroviral treatment, many South Africans die yearly of AIDS. It is important that the end-of-life needs of these people be met. This article examines the major challenges involved in providing quality end of-life care to people with AIDS in South Africa. Published reports are reviewed, as is the author's experience living and working in KwaZulu-Natal, South Africa. The issues discussed include the nature of the South African health care system, with emphasis on the scarcity of palliative care resources for AIDS patients, ineffective control of pain, models of care such as the integrated community based home care model that relies heavily on community caregivers to meet the needs of people dying of AIDS, the living conditions of AIDS patients and their families, and AIDS-related stigma. Broad recommendations are presented for improving palliative care services for people with AIDS in the South African context. PMID- 17347498 TI - Oxysterols are substrates for cholesterol sulfotransferase. AB - Oxysterols constitute a class of cholesterol derivatives that exhibit broad biological effects ranging from cytotoxicity to regulation of nuclear receptors. The role of oxysterols such as 7-ketocholesterol (7-KC) in the development of retinal macular degeneration and atheromatous lesions is of particular interest, but little is known of their metabolic fate. We establish that the steroid/sterol sulfotransferase SULT2B1b, known to efficiently sulfonate cholesterol, also effectively sulfonates a variety of oxysterols, including 7-KC. The cytotoxic effect of 7-KC on 293T cells was attenuated when these cells, which do not express SULT2B1b, were transfected with SULT2B1b cDNA. Importantly, protection from 7-KC-induced loss of cell viability with transfection correlated with the synthesis of SULT2B1b protein and the production of the 7-KC sulfoconjugate (7 KCS). Moreover, when 7-KCS was added to the culture medium of 293T cells in amounts equimolar to 7-KC, no loss of cell viability occurred. Additionally, MCF 7 cells, which highly express SULT2B1b, were significantly more resistant to the cytotoxic effect of 7-KC. We extended the range of oxysterol substrates for SULT2B1b to include 7alpha/7beta-hydroxycholesterol and 5alpha,6alpha/5beta,6beta epoxycholesterol as well as the 7alpha-hydroperoxide derivative of cholesterol. Thus, SULT2B1b, by acting on a variety of oxysterols, offers a potential pathway for modulating in vivo the injurious effects of these compounds. PMID- 17347500 TI - A prospective randomized study of corticosteroids as adjuvant drugs to opioids in advanced cancer patients. AB - This randomized controlled study evaluated the role of corticosteroids as adjuvants to opioid therapy in 76 advanced cancer patients with pain who requiring strong opioids. Patients were divided in 2 groups. Group O received conventional opioid treatment. Group OS received dexamethasone (8 mg orally) along with conventional treatment. Pain and symptom intensity, sense of well being, and opioid escalation index and distress score were recorded at weekly intervals until death. No differences in pain intensity, opioid consumption, and opioid escalation index were found in 66 patients who survived 33 to 37 days. Corticosteroids did not provide significant additional analgesia to opioids, but persistently decreased opioid-related gastrointestinal symptoms for the patients with limited survival and improved the sense of well-being for some weeks. Corticosteroid-related toxicity was minimal. Further studies with an increased sample size are necessary to detect any minimal difference in analgesia between the two groups. PMID- 17347501 TI - Acute inpatient palliative medicine in a cancer center: clinical problems and medical interventions--a prospective study. AB - The clinical characteristics and medical interventions of the 100 consecutive cancer admissions to the acute care inpatient palliative medicine unit at the Cleveland Clinic for 2 months are described. Median age was 62 years (range, 31 to 92 years). The male-female ratio was 1:1. Most admissions were referred by hematology-oncology and had prior antineoplastic therapy. Reasons for admission were symptom control and cancer-related complications. Patients underwent invasive diagnostic and therapeutic procedures, hydration, transfusions, radiation, or chemotherapy, or a combination, during their admission. Most were discharged home with hospice care or had outpatient clinic follow-up. The mortality rate was 20%. Aggressive multidisciplinary management of symptoms, disease complications, comorbid conditions, and psychosocial problems were provided. Palliative medicine physicians provided continuity of care in the outpatient clinic and at home. An acute inpatient palliative medicine unit within a tertiary level medical center has a definable and important role in comprehensive cancer care. PMID- 17347502 TI - Preliminary statistical assessment of intervention by a palliative care team working in a Japanese general inpatient unit. AB - The effectiveness of intervention by the palliative care team at the University of Tokyo Hospital was assessed using the Support Team Assessment Schedule. During the study, 316 consecutive patients with malignant tumor disease were referred to the palliative care team, which assessed 11 physical symptoms. Results were tested by paired t test to calculate 95% confidence intervals comparing the mean Support Team Assessment Schedule scores for each symptom from the first time to the last time after palliative care intervention. The study concluded that (1) intervention by a palliative care team in general inpatient units can effectively control pain, nausea, and vomiting in patients up until the terminal stage; (2) it is likely that cough is controllable in the terminal stage with intervention by a palliative care team; (3) mouth dryness, anorexia, constipation, diarrhea, fatigue, and ascites are difficult to alleviate in the long term even with palliative intervention. PMID- 17347503 TI - Medical condition is related to treatment preference in cancer patients: implications for quality assessment. AB - Ongoing communication with cancer patients about their treatment preferences is important. A survey assessing treatment preferences was distributed to 100 cancer patients who were newly diagnosed, 100 in remission after therapy, and 60 who had failed therapy/ relapsed; 100 cancer caregivers, and 100 noncancer patients attending the cancer center for benign hematologic problems. Almost 59% of respondents preferred treatment even if the chance of cure was less than 10%. Among subjects who did not have cancer, less than 50% wanted treatment under these circumstances, whereas over 70% of cancer patients who had failed treatment or relapsed wanted treatment (P=.0994). Multiple logistic regression analysis revealed that the adjusted odds of preferring aggressive treatment were less for those without cancer and those with newly diagnosed cancer than for respondents who had failed treatment or were in relapse. The preference for aggressive cancer treatment is related to medical condition. PMID- 17347504 TI - Spiritual needs of persons with advanced cancer. AB - Spiritual needs, spiritual distress, and spiritual well-being of patients with terminal illnesses can affect their quality of life. The spiritual needs of patients with advanced cancer have not been widely studied. This study assessed the spiritual needs of 90 patients with advanced cancer who were newly admitted to hospice home care. They completed a demographic data form and the Spiritual Needs Inventory shortly after hospice admission. Scores could range from a low of 17 to a high of 85; study scores were 23 to 83. Results showed great variability in spiritual needs. Being with family was the most frequently cited need (80%), and 50% cited prayer as frequently or always a need. The most frequently cited unmet need was attending religious services. Results suggest the importance of a focus on the spiritual more than the religious in providing care to patients at the end of life. PMID- 17347505 TI - Measuring interdisciplinary perceptions of collaboration on hospice teams. AB - This project modified the Index for Interdisciplinary Collaboration to create a tool that could measure perceptions of collaboration by all members of the hospice team. Questions on the 42-item instrument were reworded to be more inclusive. This new Modified Index for Interdisciplinary Collaboration (MIIC) showed strong reliability for the total instrument and the original instrument subscales. Further use and testing of this instrument is recommended. PMID- 17347506 TI - The new Israeli Law "The Dying Patient" and Relief of Suffering Units. AB - The new Israeli Law "The Dying Patient" provides avenues for possible medical, ethical, and Halachic (Jewish religious law) solutions in view of the complexity of the treatment of an end-stage dementia patient. The establishment of a hospice like setting for dementia patients in Israel, based on palliative treatment only, similar to the Jewish hospices in the United States, is extremely important. This article proposes a new, alternative approach and setting for patients with end stage dementia that could pertain to the Israeli setting and could possibly also be acceptable in other countries. Short hospitalization periods of approximately 1 month and treatment in Relief of Suffering End-of-Life With Dementia Units may be a new palliative approach and present a possible solution for coping with the burden of the suffering of end-state dementia patients, their families, and the medical and nursing staff. PMID- 17347507 TI - Defaulting oncology patient in a multispecialty state-run hospital in India. AB - A 14-year-old boy diagnosed with primitive neuroectodermal tumor of the L5 vertebra defaulted from his treatment, which significantly contributed to the progression of his disease. The possible causes of defaulting were (1) poor doctor/patient rapport, (2) inadequate communication between doctor and patient about the disease and its treatment, (3) unavailability of a "no show" defaulters' compliance program and case managers, (4) patients' economic constraints, (5) additional inconveniences because of referrals and consultations in a large multispecialty state-run hospital, and (6) patient's low education level and poor understanding of the disease and its treatment. Defaulting is multifactorial but can be contained. Good doctor/patient rapport, with emphasis on effective communication is important in improving compliance. Institutional administrative procedures should be more user-friendly. Medical institutions should consider having a "no show" defaulters' compliance program and case managers in those specialties where defaulting can adversely affect the clinical outcome. PMID- 17347508 TI - Should age limit admission to the intensive care unit? AB - People who are older than 65 years of age are the fastest growing segment of the United States population. With the projected exponential increase in the number of elderly patients and the increasing burden of chronic disease, the number of elderly patients who will require treatment in an intensive care unit is expected to increase. Owing to the elderly patient's reduced life expectancy and higher intensive care unit and hospital mortality, it could be argued that elderly patients should not be admitted to the intensive care unit. However, an analysis of available data suggests that functional elderly patients have a favorable "long-term" outcome after intensive care unit admission. This suggests that age alone should not be used in making intensive care unit triage decisions. PMID- 17347510 TI - Durable power of attorney versus the advance directive: who wins, who suffers? PMID- 17347511 TI - My father was a wonderful man. PMID- 17347512 TI - Conceptualizing Alzheimer's disease as a terminal medical illness. AB - Alzheimer's disease is a common illness of the elderly population, with an estimated prevalence of 4.5 million people in the United States and 24.3 million worldwide. Despite current pharmaceutic advances in delaying disease progression, there is no cure. This article reviews the evidence for conceptualizing Alzheimer's disease as a terminal medical illness. Discussed are principles of palliative care as applied to the patient with Alzheimer's disease and the patient's family. PMID- 17347513 TI - Protein-tyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer. AB - The protein-tyrosine phosphatase 1B (PTP1B; PTPN1) is an important regulator of mammalian metabolism and also helps control signaling by growth factors, cytokines, and extracellular matrix. Gene knockout studies in mice established PTP1B as a key negative regulator of the insulin and leptin receptors. Experiments using PTP1B(-/-) fibroblast lines, dominant-negative mutants, or small interfering RNAs indicate that PTP1B contributes to dephosphorylation of the epidermal growth factor receptor and platelet-derived growth factor receptors as well. However, PTP1B also may have some positive (signal enhancing) roles downstream of some growth factor receptors and integrins. Previous studies indicated that PTP1B is overexpressed in a significant subset of breast and ovarian cancers, especially in those overexpressing HER2/Neu (HER2(+) tumors). However, experiments using tissue culture cells yield conflicting results on the effects of PTP1B in HER2 signaling, leaving the consequences of PTP1B overexpression for breast carcinogenesis unclear. To determine how PTP1B deficiency affects HER2-evoked breast tumorigenesis, we generated mouse mammary tumor virus (MMTV)-NeuNT transgenic mice lacking one or both alleles of PTP1B. Although heterozygous loss of PTP1B has no effect on tumorigenesis, homozygous PTP1B deficiency dramatically delays or prevents the onset of MMTV-NeuNT-evoked breast tumors. The effects of PTP1B deficiency correlate with defective extracellular signal-regulated kinase activation in preneoplastic mammary glands from compound mutant mice. In contrast, PTP1B deficiency has no effect on MMTV polyoma middle T tumorigenesis. Our data raise the possibility that PTP1B inhibitors may be chemopreventative for some forms of breast cancer. PMID- 17347514 TI - A tribute to George F. Vande Woude, a man of character: 2006 Scientific Symposium Winning the War against Cancer: from Genomics to Bedside and Back. PMID- 17347518 TI - Surprising arginine biosynthesis: a reappraisal of the enzymology and evolution of the pathway in microorganisms. AB - Major aspects of the pathway of de novo arginine biosynthesis via acetylated intermediates in microorganisms must be revised in light of recent enzymatic and genomic investigations. The enzyme N-acetylglutamate synthase (NAGS), which used to be considered responsible for the first committed step of the pathway, is present in a limited number of bacterial phyla only and is absent from Archaea. In many Bacteria, shorter proteins related to the Gcn5-related N acetyltransferase family appear to acetylate l-glutamate; some are clearly similar to the C-terminal, acetyl-coenzyme A (CoA) binding domain of classical NAGS, while others are more distantly related. Short NAGSs can be single gene products, as in Mycobacterium spp. and Thermus spp., or fused to the enzyme catalyzing the last step of the pathway (argininosuccinase), as in members of the Alteromonas-Vibrio group. How these proteins bind glutamate remains to be determined. In some Bacteria, a bifunctional ornithine acetyltransferase (i.e., using both acetylornithine and acetyl-CoA as donors of the acetyl group) accounts for glutamate acetylation. In many Archaea, the enzyme responsible for glutamate acetylation remains elusive, but possible connections with a novel lysine biosynthetic pathway arose recently from genomic investigations. In some Proteobacteria (notably Xanthomonadaceae) and Bacteroidetes, the carbamoylation step of the pathway appears to involve N-acetylornithine or N-succinylornithine rather than ornithine. The product N-acetylcitrulline is deacetylated by an enzyme that is also involved in the provision of ornithine from acetylornithine; this is an important metabolic function, as ornithine itself can become essential as a source of other metabolites. This review insists on the biochemical and evolutionary implications of these findings. PMID- 17347517 TI - Replication fork stalling at natural impediments. AB - Accurate and complete replication of the genome in every cell division is a prerequisite of genomic stability. Thus, both prokaryotic and eukaryotic replication forks are extremely precise and robust molecular machines that have evolved to be up to the task. However, it has recently become clear that the replication fork is more of a hurdler than a runner: it must overcome various obstacles present on its way. Such obstacles can be called natural impediments to DNA replication, as opposed to external and genetic factors. Natural impediments to DNA replication are particular DNA binding proteins, unusual secondary structures in DNA, and transcription complexes that occasionally (in eukaryotes) or constantly (in prokaryotes) operate on replicating templates. This review describes the mechanisms and consequences of replication stalling at various natural impediments, with an emphasis on the role of replication stalling in genomic instability. PMID- 17347520 TI - Biosynthesis of ether-type polar lipids in archaea and evolutionary considerations. AB - This review deals with the in vitro biosynthesis of the characteristics of polar lipids in archaea along with preceding in vivo studies. Isoprenoid chains are synthesized through the classical mevalonate pathway, as in eucarya, with minor modifications in some archaeal species. Most enzymes involved in the pathway have been identified enzymatically and/or genomically. Three of the relevant enzymes are found in enzyme families different from the known enzymes. The order of reactions in the phospholipid synthesis pathway (glycerophosphate backbone formation, linking of glycerophosphate with two radyl chains, activation by CDP, and attachment of common polar head groups) is analogous to that of bacteria. sn Glycerol-1-phosphate dehydrogenase is responsible for the formation of the sn glycerol-1-phosphate backbone of phospholipids in all archaea. After the formation of two ether bonds, CDP-archaeol acts as a common precursor of various archaeal phospholipid syntheses. Various phospholipid-synthesizing enzymes from archaea and bacteria belong to the same large CDP-alcohol phosphatidyltransferase family. In short, the first halves of the phospholipid synthesis pathways play a role in synthesis of the characteristic structures of archaeal and bacterial phospholipids, respectively. In the second halves of the pathways, the polar head group-attaching reactions and enzymes are homologous in both domains. These are regarded as revealing the hybrid nature of phospholipid biosynthesis. Precells proposed by Wachtershauser are differentiated into archaea and bacteria by spontaneous segregation of enantiomeric phospholipid membranes (with sn-glycerol 1-phosphate and sn-glycerol-3-phosphate backbones) and the fusion and fission of precells. Considering the nature of the phospholipid synthesis pathways, we here propose that common phospholipid polar head groups were present in precells before the differentiation into archaea and bacteria. PMID- 17347521 TI - Insertion sequence diversity in archaea. AB - Insertion sequences (ISs) can constitute an important component of prokaryotic (bacterial and archaeal) genomes. Over 1,500 individual ISs are included at present in the ISfinder database (www-is.biotoul.fr), and these represent only a small portion of those in the available prokaryotic genome sequences and those that are being discovered in ongoing sequencing projects. In spite of this diversity, the transposition mechanisms of only a few of these ubiquitous mobile genetic elements are known, and these are all restricted to those present in bacteria. This review presents an overview of ISs within the archaeal kingdom. We first provide a general historical summary of the known properties and behaviors of archaeal ISs. We then consider how transposition might be regulated in some cases by small antisense RNAs and by termination codon readthrough. This is followed by an extensive analysis of the IS content in the sequenced archaeal genomes present in the public databases as of June 2006, which provides an overview of their distribution among the major archaeal classes and species. We show that the diversity of archaeal ISs is very great and comparable to that of bacteria. We compare archaeal ISs to known bacterial ISs and find that most are clearly members of families first described for bacteria. Several cases of lateral gene transfer between bacteria and archaea are clearly documented, notably for methanogenic archaea. However, several archaeal ISs do not have bacterial equivalents but can be grouped into Archaea-specific groups or families. In addition to ISs, we identify and list nonautonomous IS-derived elements, such as miniature inverted-repeat transposable elements. Finally, we present a possible scenario for the evolutionary history of ISs in the Archaea. PMID- 17347524 TI - Factors associated with young children's self-perceived physical competence and self-reported physical activity. AB - The aim of this study was to identify factors associated with self-reported physical activity (PA), self-perceived physical fitness and competence in physical education (PE) among young children. The study included physical tests, anthropometric measures and a questionnaire. The study group comprised 206 children (114 boys and 92 girls, aged 8-12 years). Positive Odds Ratio was used in the logistic regression analyses. High level of self-reported PA was associated with membership of sport clubs and high self-perceived physical fitness. Variables associated with high self-perceived competence in PE were low age, high physical performance, living with both parents, high self-perceived physical fitness, male gender and enjoying PE. Variables associated with high self-perceived physical fitness were low age, high performance in endurance running, high self-reported PA, positive self-perceived body function and high self-perceived competence in PE. Correlations between children's self-perceived competence in PE and actual measured physical performance, between the self perceived fitness and endurance performance and between self-reported PA and physical performance could be seen as a form of concurrent validity. One implication of the study for practitioners might be that children's own perceptions of their physical competence and activity levels could be used to roughly identify groups of children who are at risk of remaining physically inactive and therefore more prone to be unhealthy. PMID- 17347525 TI - A video-based lifestyle intervention and changes in coronary risk. AB - If population-wide improvements in nutrition and physical activity behavior are to be made, behavior change interventions must use a variety of media. This study examines whether participation in a facilitator-based video version of the Coronary Health Improvement Project could significantly reduce coronary risk. A total of 28 video classes conducted in worksite, medical and community settings were used to teach 763 middle-aged adults, ages 30-79 years, about healthy lifestyles. Four to 8 weeks after baseline, follow-up measures were taken. Demographic and biometric data [body weight, body mass index (BMI), blood lipids, blood pressure and fasting blood glucose] were gathered. The class participants were evaluated in aggregate and showed significant improvements in body weight, BMI, resting heart rate, total cholesterol, low-density lipoprotein, triglycerides and fasting blood glucose. Males demonstrated greater improvement than females, and individuals with higher baseline health risks experienced the greatest reductions in risk. This video lifestyle change program appears to help participants make important lifestyle changes. For individuals empowered to make better choices regarding diet and exercise, significant improvements occurred in most coronary risk factors in as little as 4-6 weeks. PMID- 17347526 TI - A bias against disconfirmatory evidence is associated with delusion proneness in a nonclinical sample. AB - Previous work has suggested that a bias against disconfirmatory evidence (BADE) may be associated with the schizophrenia spectrum. The current investigation focused on whether a BADE (1) overlaps with traditional measures of memory and executive functions or selectively taps into a unique aspect of cognition and (2) is correlated with delusional ideation but not with other aspects of schizotypy. Sixty-eight undergraduate students were administered the Schizotypal Personality Questionnaire (SPQ), the BADE test, the Rey Auditory Verbal Learning Test (RAVLT), the Wisconsin Card Sorting Test (WCST), the Trail Making Tests A and B (TMT), and tests used to estimate IQ. Factor analysis of all cognition measures resulted in a 6-factor solution, 4 of which reflected the 4 domains of neuropsychological tests (WCST, RAVLT, TMT, and IQ), and 2 of which reflected different aspects of the BADE test: Initial Belief and Integration of Disconfirmatory Evidence. This solution suggests that BADE measures were independent from the other cognitive domains measured. Integration of Disconfirmatory Evidence was the only factor that correlated with delusion content subscales of the SPQ, providing support for the contribution of a BADE to delusional ideation. PMID- 17347519 TI - Central roles of small GTPases in the development of cell polarity in yeast and beyond. AB - SUMMARY: The establishment of cell polarity is critical for the development of many organisms and for the function of many cell types. A large number of studies of diverse organisms from yeast to humans indicate that the conserved, small molecular-weight GTPases function as key signaling proteins involved in cell polarization. The budding yeast Saccharomyces cerevisiae is a particularly attractive model because it displays pronounced cell polarity in response to intracellular and extracellular cues. Cells of S. cerevisiae undergo polarized growth during various phases of their life cycle, such as during vegetative growth, mating between haploid cells of opposite mating types, and filamentous growth upon deprivation of nutrition such as nitrogen. Substantial progress has been made in deciphering the molecular basis of cell polarity in budding yeast. In particular, it becomes increasingly clear how small GTPases regulate polarized cytoskeletal organization, cell wall assembly, and exocytosis at the molecular level and how these GTPases are regulated. In this review, we discuss the key signaling pathways that regulate cell polarization during the mitotic cell cycle and during mating. PMID- 17347527 TI - Effects of endurance training and acute Doxorubicin treatment on rat heart mitochondrial alterations induced by in vitro anoxia-reoxygenation. AB - Endurance training (ET) and adriamycin (ADR) treatment are two conditions that have been described as triggering metabolic alterations within the myocardium. ADR is an anti-neoplastic agent with notorious cardiotoxicity, most likely because it increases oxidative stress. ET and/or ADR treatment can induce metabolic and signaling alterations affording cross-tolerance against several insults such as ischemia and reperfusion. The objective of the present work was to investigate whether heart mitochondria isolated from rats submitted to ET with or without ADR treatment were more or less susceptible to in vitro anoxia reoxygenation (AR) when compared with control rats. Twenty-four male Wistar rats were assigned into four groups (n = 6 each): control (C), ADR 20 mg-kg-1), 14 wk ET (T), and T+ADR. Respiratory parameters and oxidative damage were determined before and after 1 min anoxia followed by 4 min reoxygenation. Basal heat shock proteins (HSPs)60 and -70 and antioxidant enzymes' activity were measured. ADR by itself decreased state 3 and respiratory control ratio (RCR), as opposed to ET by itself, which improved state 3 and RCR. As expected, AR impaired state 3 and 4, RCR, and ADP/O in the C group (p > 0.05). In the ADR group, AR did not induce any alteration in RCR and in ADP/O values. ET in the absence of ADR treatment prevented the impairment in RCR and ADP/O and in state 4 induced by AR. Also, despite the fact that state 3 respiration after AR was lower in all groups, it was significantly higher in the T than in the C group. Increased mitochondrial carbonyls and malondialdehyde (MDA) after AR were only found in the C group. Also, following AR, both carbonyls and MDA levels were lower in the T and in the T+ADR than in C and ADR groups, respectively. HSP60 levels were higher in the ADR, T, and T+ADR than in the C group (2.5- fold, 2-fold, and 1.9-fold increase, respectively). HSP70 increased twofold in the T and T+ADR groups. ET augmented 1.5-fold the activity of superoxide dismutase. The present work demonstrates that both ET and ADR treatment induced myocardial alterations that interfere with in vitro mitochondrial responses to AR. PMID- 17347523 TI - Functional taxonomy of bacterial hyperstructures. AB - The levels of organization that exist in bacteria extend from macromolecules to populations. Evidence that there is also a level of organization intermediate between the macromolecule and the bacterial cell is accumulating. This is the level of hyperstructures. Here, we review a variety of spatially extended structures, complexes, and assemblies that might be termed hyperstructures. These include ribosomal or "nucleolar" hyperstructures; transertion hyperstructures; putative phosphotransferase system and glycolytic hyperstructures; chemosignaling and flagellar hyperstructures; DNA repair hyperstructures; cytoskeletal hyperstructures based on EF-Tu, FtsZ, and MreB; and cell cycle hyperstructures responsible for DNA replication, sequestration of newly replicated origins, segregation, compaction, and division. We propose principles for classifying these hyperstructures and finally illustrate how thinking in terms of hyperstructures may lead to a different vision of the bacterial cell. PMID- 17347528 TI - Cardiac overexpression of metallothionein attenuates chronic alcohol intake induced cardiomyocyte contractile dysfunction. AB - Chronic alcohol ingestion leads to alcoholic cardiomyopathy manifested by ventricular dysfunction and heart failure. Although accumulation of reactive oxygen species may play a role in alcohol-induced heart injury, direct impact of enhanced antioxidant defense on pathogenesis of alcoholic cardiomyopathy has not been elucidated. This study was designed to examine the effect of transgenic overexpression of the free radical scavenger metallothionein on alcohol-induced cardiac contractile dysfunction. Wild-type FVB and metallothionein mice were placed on a 4% alcohol or control diet for 12 wk. Cardiac contractile function was evaluated in cardiomyocytes including peak shortening (PS), time-to-peak shortening, time-to-90% relengthening (TR90), maximal velocity of shortening/relengthening (+/-dL/dt), intracellular Ca2+ rise (change in fura-2 fluorescent intensity [DeltaFFI]) and intracellular Ca2+ decay rate. Intracellular Ca2+ cycling proteins including sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a), Na+-Ca2+ exchanger (NCX) and phospholamban were assessed using Western blot analysis. Alcohol intake depressed PS, +/-dL/dt, and DeltaFFI, increased baseline fura-2 fluorescence intensity (FFI), and prolonged intracellular Ca2+ decay and TR90, all of which with the exception of DeltaFFI were abrogated by metallothionein. Enhanced stimulating frequency caused lessened PS decline at 1.0 Hz from FVB ethanol group, which was not affected by metallothionein. Immunoblotting data showed reduced SERCA2a, NCX and phospholamban expression in FVB group consuming alcohol. All of these alcohol- induced changes in cardiac proteins were nullified by the metallothionein transgene. In summary, our findings suggest a beneficial role of antioxidants in alcohol-induced cardiomyocyte dysfunction. PMID- 17347529 TI - Emotional stress and reversible myocardial dysfunction. AB - A growing body of clinical and experimental literature supports a strong association between emotional stress and adverse outcomes from CVD. Effects of emotional stress on coronary blood flow and cardiac arrhythmias provide only a partial explanation. A direct impact of emotional stress on myocardial function has recently received attention as a result of reports of patients presenting with new onset of unexplained reversible heart failure following episodes of emotional stress. Potential mechanisms responsible for myocardial dysfunction following emotional stress remain to be elucidated. This review will explore potential pathophysiologic mechanisms linking emotional stress to adverse cardiovascular outcomes beginning with primary and secondary risk factors and leading to direct effects of emotional stress on reversible myocardial dysfunction. PMID- 17347530 TI - Fresh gasoline emissions, not paved road dust, alter cardiac repolarization in ApoE-/- mice. AB - Fresh vehicular emissions potentially represent a ubiquitous environmental concern for cardiovascular health. We compared electrocardiographic effects of fresh gasoline engine emissions with resuspended paved road dust in a mouse model of coronary insufficiency. Apolipoprotein E (ApoE)-/- mice on a high fat diet were exposed by whole-body inhalation to either gasoline emissions at 60 microg/m3 particulate matter (PM), an equivalent atmosphere with particles filtered out of the whole exhaust, or paved road dust at 0.5 and 3.5 mg /m3 for 6 h/d for 3 d. Radiotelemetry recordings of electrocardiogram (ECG) were analyzed for changes in T-wave morphology (QT interval, T-wave amplitude, and T-wave Area). Following exposures, lung lavage and blood samples were obtained to assay for markers of pulmonary and systemic inflammation. No exposure induced significant changes in heart rate and only the high concentration of road dust induced signs of pulmonary inflammation. T-wave area exhibited significant deviation from baseline values during exposure to gasoline exhaust particulates, but not to either concentration of road dust or gasoline emissions sans particulates. Gasoline-exposed mice demonstrated elevated plasma endothelin-1, but did not cause systemic inflammation. These data support the hypothesis that freshly-generated engine emissions, as opposed to resuspended paved road dust, may drive cardiac effects that have been observed at road-sides in the environment. The absence of ECG effects for both very high concentrations of road dust PM and equivalent concentrations of the vapor/gas phase of gasoline engine exhaust further indicate the specific risk conferred by fresh vehicular PM. PMID- 17347531 TI - Serum cardiac troponin T as a biomarker for acute myocardial injury induced by low doses of isoproterenol in rats. AB - In rats, high doses of isoproterenol (Iso) have caused acute myocardial lesions and increased serum levels of cardiac troponin T (cTnT). We determined whether low doses of Iso also cause cardiac alterations and whether monitoring cTnT levels could detect this injury. Rats received 8 to 500 microg/kg Iso and were followed for 3 to 48 h. Lesion severity was scored from 0 to 5. Within 3 h, mean cTnT was elevated in all 29 rats receiving 8, 16, 32, or 64 microg/kg Iso (0.20 to 0.28 ng/mL ), but minimal lesions occurred in only two animals. However, by 6 h, cardiac lesions and increases in serum cTnT (mean = 0.21 to 0.23 ng/mL) were observed in all 14 rats receiving 32 or 64 microg/kg Iso. Doses of 125, 250, or 500 microg/kg Iso caused more significant increases in cTnT levels and marked myocardial lesions that reached a peak 3 to 6 h after dosing. The magnitude of the lesions and cTnT levels declined between 12 and 48 h post treatment. Thus, a range of low Iso doses can cause myocardial lesions, and serum cTnT levels can be monitored to detect the onset and progression of this type of acute cardiac injury in rats; however, careful attention to dosing and sampling times is critical to interpretation. PMID- 17347532 TI - The Genetics of PPARG and the Skeleton. AB - Osteoporosis is a complex metabolic bone disorder. Recently it has been appreciated that the "obesity in bone" phenomenon occurs at the expense of bone formation, and that is a key component of the pathology of this disease. Mouse models with altered bone expression levels of peroxisome proliferator-activated receptor gamma (PPARG) impact bone formation, but genetic studies connecting PPARG polymorphisms to skeletal phenotypes in humans have proven to be less than satisfactory. One missense polymorphism in exon one has been linked to low bone mineral density (BMD), but the most studied polymorphism, Pro12Ala, has not yet been examined in the context of skeletal phenotype. The studies to date are a promising start in leading to our understanding of the genetic contribution of PPARG to the phenotypes of BMD and fracture risk. PMID- 17347534 TI - Identification of a Gene Sharing a Promoter and Peroxisome Proliferator-Response Elements With Acyl-CoA Oxidase Gene. AB - Many mammalian genes are clustered on the genomes, and hence the genes in the same cluster can be regulated through a common regulatory element. We indeed showed previously that the perilipin/PEX11alpha gene pair is transactivated tissue-selectively by PPARgamma and PPARalpha, respectively, through a common binding site. In the present study, we identified a gene, named GSPA, neighboring a canonical PPAR target, acyl-CoA oxidase (AOX) gene. GSPA expression was induced by a peroxisome proliferator, Wy14,643, in the liver of wild-type mice, but not PPARalpha-null mice. GSPA and AOX share the promoter and two peroxisome proliferator-response elements. GSPA mRNA was also found in the heart and skeletal muscle, as well as 3T3-L1 cells. GSPA encodes a protein of 161 amino acids that is enriched in 3T3-L1 cells. Even other gene pairs might be regulated through common sequence elements, and conversely it would be interesting how each gene is aptly regulated in clusters. PMID- 17347533 TI - Thiazolidinediones and Fertility in Polycystic Ovary Syndrome (PCOS). AB - Polycystic ovary syndrome (PCOS) is the most frequent cause of female infertility. The treatment of PCOS patients with insulin sensitizers, such as metformin or thiazolidinediones, increases the ovulation rate and the number of successful pregnancies. The positive action of the insulin-sensitizing treatments could be explained by a decrease in the peripheral insulin resistance but also by a direct action at the ovarian level. We report in this review different hypotheses of thiazolidinediones actions to improve PCOS (steroid secretion by ovarian cells ; insulin sensitivity in muscle and adipocyte and fat redistribution). PMID- 17347536 TI - Tobacco control in India. AB - Portuguese introduced tobacco to India 400 years ago. Ever since, Indians have used tobacco in various forms. Sixty five per cent of all men and 33% of all women use tobacco in some form. Tobacco causes over 20 categories of fatal and disabling diseases including oral cancer. By 2020 it is predicted that tobacco will account for 13% of all deaths in India. A major step has to be taken to control what the World Health Organization, has labeled a 'smoking epidemic' in developing countries. India's anti-tobacco legislation, first passed in 1975, was largely limited to health warnings and proved to be insufficient. A new piece of national legislation, proposed in 2001, represents an advance including banning smoking in public places, advertising and forbidding sale of tobacco to minors. Preventing the use of tobacco in various forms as well as treating nicotine addiction is the major concern of dentists and physicians. The dental encounter probably constitutes a "teachable moment" when the patient is receptive to counseling about life- style issues. Both policy makers and health professionals must work together for achieving a smoke free society for our coming generations. PMID- 17347537 TI - The detection of eight putative periodontal pathogens in adult and rapidly progressive periodontitis patients: an institutional study. AB - PURPOSE: Periodontal disease is a commonly prevalent problem faced alike by both the developed and third world countries but showing wide variations in prevalence and severity across different geographical areas. The purpose was to identify Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Ekinella corrodens (Ec), Campylobacter rectus (Cr), Bacteroides forsythus (Bf), Treponema denticola (Td) and Fusobacterium nucleatum (Fn) in Indian adult periodontitis and rapidly progressive periodontitis patients. MATERIALS AND METHODS: Paper points were used to collect the sample from 28 sites in both adult periodontitis and rapidly progressive periodontitis (8 healthy/20 diseased sites) patients and DNA analysis done. The categorical data was analysed by Fishers exact test and difference in the clinical parameters was tested by Mann-Whitney test. RESULTS: In healthy sites of adult and rapidly progressive periodontitis patients, Aa, Ec, Bf and Aa, Pg, Pi, Td, Fn were detected respectively. However, when diseased and healthy sites were compared in both adult periodontitis and rapidly progressive periodontitis patients respectively, only Pg( P =0.004), Cr( P =0.04), Fn( P =0.014) and Pg( P =0.002), Cr( P =0.02), Fn( P =0.008) were statistically significant. CONCLUSION: The prevalence of the microorganisms correlate with the clinical parameters like probing depth and bleeding on probing as seen in the Japanese and Western periodontitis patients' population. PMID- 17347538 TI - Areca nut use among rural residents of Sriperambudur Taluk: a qualitative study. AB - OBJECTIVE: The main objective of the study was to understand the perceptions of the residents of rural part of Sriperambudur Taluk, regarding areca nut use. This article discusses the findings of in-depth interviews and focus group discussions at rural part of Sriperambudur Taluk. MATERIALS AND METHODS: A community-based survey was conducted using qualitative methods. Out of 168 villages, 11 were randomly chosen. Fifteen in-depth interviews and five focus group discussions were conducted. Only those above 10 years of age and who used areca nut either in processed or un-processed form were included in the study. RESULTS: Among different forms of areca nut products, the use of Hans, which is a commercial flavored product containing areca nut, tobacco and other ingredients is believed to be the most prevalent habit in all the age groups. Chewing areca nut is the initiating habit, leading to other habits such as smoking and consuming alcoholic beverages. Residents less than 30 years of age chew areca nut products for fun or because of peer pressure whereas the 30 to 50 year olds get habituated due to reasons such as boredom and family problems. Although there is awareness regarding the ill-effects of tobacco use, there is not much awareness regarding areca nut. According to the residents, the community has not given enough thought regarding areca nut products and therefore no action has been taken to mitigate this high-risk behavior. CONCLUSION: It is the perception of the community that there is an increasing trend in the use of areca nut especially the commercial forms such as Hans , in rural Tamilnadu. Habit gets initiated at a very young age; therefore age specific intervention programs should be implemented. Periodic research should be conducted to better understand the changing trends of chewing areca nut products. PMID- 17347522 TI - Colicin biology. AB - Colicins are proteins produced by and toxic for some strains of Escherichia coli. They are produced by strains of E. coli carrying a colicinogenic plasmid that bears the genetic determinants for colicin synthesis, immunity, and release. Insights gained into each fundamental aspect of their biology are presented: their synthesis, which is under SOS regulation; their release into the extracellular medium, which involves the colicin lysis protein; and their uptake mechanisms and modes of action. Colicins are organized into three domains, each one involved in a different step of the process of killing sensitive bacteria. The structures of some colicins are known at the atomic level and are discussed. Colicins exert their lethal action by first binding to specific receptors, which are outer membrane proteins used for the entry of specific nutrients. They are then translocated through the outer membrane and transit through the periplasm by either the Tol or the TonB system. The components of each system are known, and their implication in the functioning of the system is described. Colicins then reach their lethal target and act either by forming a voltage-dependent channel into the inner membrane or by using their endonuclease activity on DNA, rRNA, or tRNA. The mechanisms of inhibition by specific and cognate immunity proteins are presented. Finally, the use of colicins as laboratory or biotechnological tools and their mode of evolution are discussed. PMID- 17347539 TI - Comparison of morbidity following the removal of mandibular third molar by lingual split, surgical bur and simplified split bone technique. AB - BACKGROUND: The methods frequently used for surgical removal of impacted third molars are bur technique, lingual split and simplified split bone technique. The morbidity rates following the use of these different surgical techniques are not completely resolved. The use of a surgical method with minimum postoperative complication is needed. AIM: This study was conducted to compare the morbidity rates of the three different surgical techniques and their efficacy with regard to postoperative pain, swelling, labial and lingual sensation. MATERIALS AND METHODS: Ninety patients with a symptomatic impacted mandibular third molar with the age range of 14-62 years were divided into three groups of 30 patients each for surgical bur technique, lingual split technique and simplified split bone technique. All patients were operated by the same surgeon under local anesthesia (2% lignocaine) in the dental chair. The severity of pain and swelling was recorded on a visual analogue scale and the presence or absence of sensory disturbance at 6, 24, 48 hours and seven days after operation. The pain was scored according to a visual analogue 4-point scale. Patients were asked to indicate which side was more swollen and to record this assessment on the swelling scale. RESULTS: Lingual split technique was more painful than the other two techniques. Surgical bur technique had more swelling than the other two techniques. Labial and lingual sensations were not altered in all the techniques. CONCLUSION: The simplified split bone technique had the least morbidity than the lingual split and surgical bur technique. PMID- 17347540 TI - Malignant peripheral nerve sheath tumour: an elusive diagnosis. AB - Malignant peripheral nerve sheath tumour (MPNST) also termed as spindle cell malignancy of the peripheral nerve Schwann cells or neurogenic sarcoma, represents approximately 10% of all soft tissue sarcomas. This tumour is usually found in the lower extremities and only 10-12% of all lesions occur in the head and neck region, which makes it a rare entity. The diagnosis of MPNST has been described as one of the most difficult and elusive diagnosis in the soft tissue diseases because of its non-specific presentation both clinically and histopathologically. This was overcome by the use of immunohistochemistry. A case of MPNST of the left maxillary antrum in a 45 -year -old male patient is reported. PMID- 17347541 TI - Klestadt's cyst: a rarity. AB - Klestadt's cyst, more commonly known as the nasolabial cyst is an uncommon, non odontogenic, soft tissue cyst characterized by its extra osseous location in the nasal alar region. Following its description first by Zukuerkandl in 1882, only 267 cases have been found in English literature. A case of nasolabial cyst in a 30-year-old female patient is presented. PMID- 17347542 TI - Systemic sclerosis. AB - Systemic sclerosis (scleroderma) is a rare generalized disorder of connective tissue origin. This condition is predominantly a clinical diagnosis, based on the clinical signs and symptoms. Here is a case report of 26-year-old female patient with the classical features of this disease. This case is reported for its rarity and variable expressivity. This article also reviews the literature of this uncommon condition. PMID- 17347543 TI - Chondroectodermal dysplasia (Ellis van Creveld syndrome): a report of three cases with review of literature. AB - Chondroectodermal dysplasia is a rare mesenchymal - ectodermal dysplasia first described in 1940 by Richard W.B. Ellis and Simon van Creveld now known as Ellis van Creveld syndrome. It is also known as Mesvectodermal dysplasia. Majority of cases were characteristically seen in one particular inbred population from the Amish community of Lancaster County, Pennsylvania, U.S.A. The syndrome manifests with several skeletal anomalies, oral mucosal and dental anomalies, congenital cardiac defects and nail dysplasia. Ellis van Creveld syndrome may be differentiated from other chondrodystrophies like achondroplasia, chondroplasia punctata, asphyxiating thorasic dystrophy and Morquio's syndrome. The presence of oral mucosal and dental alterations like notching of the lower alveolar process, fusion of the upper lip with gingival mucosal margin, occasional presence of neonatal teeth, oligodontia and conical shape of anterior teeth will confirm the diagnosis of Ellis van Creveld syndrome and hence its importance to dentists. PMID- 17347544 TI - Prosthetic rehabilitation of a completely edentulous patient with palatal insufficiency. AB - This article presents a case report of a completely edentulous patient with palatal insufficiency successfully rehabilitated with closed hollow bulb obturator prosthesis and also describes a simple technique for fabricating a two piece hollow bulb obturator that allows for control of the bulb's wall thickness and weight of the prosthesis. PMID- 17347545 TI - MB2 in maxillary second molar. AB - Occurrence of the second mesiobuccal canal (MB2) is a frequent finding. Literary reports have shown it to be found more in the cases of the maxillary first molar. However the maxillary second molars have also been found with this variation in a number of canals. This paper presents a case report on the occurrence of a second mesiobuccal canal or the MB2 in the maxillary second molar. PMID- 17347546 TI - Neuroendocrine functions of melanocytes: beyond the skin-deep melanin maker. AB - The skin is armored with "dead cells", the stratum corneum, and is continuously exposed to external stressful environments, such as atmospheric oxygen, solar radiations, and thermal and chemical insults. Melanocytes of neural crest origin are located in the skin, eye, inner ear, and leptomeninges. Melanin pigment in the skin is produced by melanocytes under the influence of various endogenous factors, derived from neighboring keratinocytes and underlying fibroblasts. The differentiation and functions of melanocytes are regulated at multiple processes, including transcription, RNA editing, melanin synthesis, and the transport of melanosomes to keratinocytes. Impairment at each step causes the pigmentary disorders in humans, with the historical example of oculocutaneous albinism. Moreover, heterozygous mutations in the gene coding for microphthalmia-associated transcription factor, a key regulator for melanocyte development, are associated with Waardenburg syndrome type 2, an auditory-pigmentary disorder. Sun tanning, melasma, aging spots (lentigo senilis), hair graying, and melanoma are well-known melanocyte-related pathologies. Melanocytes therefore have attracted much attention of many ladies, makeup artists and molecular biologists. More recently, we have shown that lipocalin-type prostaglandin D synthase (L-PGDS) is expressed in melanocytes but not in other skin cell types. L-PGDS generates prostaglandin D2 and also functions as an inter-cellular carrier protein for lipophilic ligands, such as bilirubin and thyroid hormones. Thus, melanocytes may exert hitherto unknown functions through L-PGDS and prostaglandin D2. Here we update the neuroendocrine functions of melanocytes and discuss the possible involvement of melanocytes in the control of the central chemosensor that generates respiratory rhythm. PMID- 17347547 TI - Classification of patients complaining of sick house syndrome and/or multiple chemical sensitivity. AB - Sick house syndrome (SHS) is a Japanese concept derived from sick building syndrome (SBS), however SHS includes a broader scope of sickness than does SBS. Symptoms of SHS/SBS disappear after leaving the sick house/building, while symptoms of multiple chemical sensitivity (MCS) are elicited by the chance of chemical exposure after leaving the sick house/building. To establish the concept of SHS, we propose to introduce a new classification for SHS. A total of 214 patients complaining of SHS and/or MCS were independently classified using a new classification by clinical ecologists who are experienced physicians with expert knowledge of clinical ecology and general physicians according to disease pathogenesis from clinical records. The classification is as follows: type 1 (symptoms of chemical intoxication), type 2 (symptoms developed possibly due to chemical exposure), type 3 (symptoms developed not because of chemical exposure but rather because of psychological or mental factors), and type 4 (symptoms developed due to allergies or other diseases). The agreements on the classification made by clinical ecologists and general physicians reached 77.1% (Cohen's kappa=0.631), suggesting that this new classification was both apt and accurate. Relations between SHS and allergy/MCS were also studied. The cases classified as SHS type 4 more frequently had allergic past histories than did other types. The proportion of possible MCS cases was higher in the chemical induced SHS group (types 1 and 2) than in other types among male patients. For the universal use in clinical practice, it is necessary to prepare helpful diagnostic criteria of this SHS classification based on pathogenesis and carry our study forward all over the country. PMID- 17347548 TI - Prediction of prognosis in patients with epidural hematoma by a new stereological method. AB - Epidural hematoma (EH) is a serious clinical event observed in 2% of head trauma patients. Studies regarding the effects of epidural hematoma volume (EHV) on prognosis are not sufficient. In this study, we applied the volume fraction approach of the stereological method to estimate the hematoma to brain volume fraction (HBVF), and investigated the relation between the HBVF and prognosis. Fifty-nine EH patients (46 male and 13 female subjects, with average age of 21 years) admitted to the emergency clinic were included. The HBVF was estimated on the printed films of cranial computed tomography scans. For this purpose, common point counting grids were superimposed over the scan frames. According to the clinical results, patients were divided into three groups as complete recovery (43), disability (8) and exitus (8). The HBVF was compared with the clinical results. HBVF was determined as 4.6% in the patients with recovery, 8.1% in disability, and 7.6% in exitus patients. The HBVF values were lowest in recovery patients, and the difference between the recovery and the other two groups was statistically significant (p=0.007). However, there was no statistically significant difference in HBVF between disability and exitus patients (p>0.05). In conclusion, the HBVF can be an important tool to determine prognosis, and it can be measured using the volume fraction approach of stereological methods as developed in the present study. PMID- 17347549 TI - Detection of Y chromosomal material in patients with a 45,X karyotype by PCR method. AB - A 45,X karyotype is one of the common chromosomal abnormalities characterized by short stature, lack of development of secondary sexual characteristics, webbed neck and cubitus valgus. This phenotype was described by Turner in 1938 and was called Turner syndrome (TS). About 40-60% of the patients with TS phenotype have a 45,X karyotype, the rest either have a structurally abnormal X or Y chromosome or mosaicism with a second cell line. Determination of Y chromosome derivatives in patients with a 45,X karyotype is important for the management of these patients due to increased risk of gonadoblastoma. Low level mosaicism of Y chromosome may be missed by cytogenetic methods. The aim of our study is to analyze cryptic Y chromosome derivatives using Y specific sequences in 40 Turkish patients with a pure 45,X karyotype. Fourteen different Y specific sequences along the Y chromosome were selected for the detection of cryptic Y chromosome material by PCR analysis. The present study demonstrated that 2 patients with a 45,X karyotype (5%) have Y specific sequences except sex related region Y (SRY). One of them had displayed enhanced virilisation whereas other showed no virilisation. In conclusion, it has been found by PCR analysis that 5% of patients with a 45,X karyotype have Y chromosome sequences in the absence of any marker chromosome by cytogenetic analysis. The data also suggest that the patients with a 45,X karyotype should be analyzed for the presence of Y chromosome derivatives by sensitive methods, such as PCR, in order to calculate the future risk of developing gonadoblastoma. PMID- 17347550 TI - Association of TNF-alpha gene promoter C-857T polymorphism with higher serum LDL cholesterol levels and carotid plaque formation in Japanese patients with type 2 diabetes. AB - Little has been known about the role of tumor necrosis factor-alpha (TNF-alpha) gene polymorphisms in metabolic syndrome and atherosclerosis in type 2 diabetes, although TNF-alpha was reported to be involved in these conditions. We examined the association of TNF-alpha gene promoter polymorphisms, G-238A, G-308A, C-857T, C-863A, and T-1031C, with metabolic syndrome and surrogate markers of atherosclerosis in Japanese patients with type 2 diabetes. DNA was obtained from 162 patients and TNF-alpha gene promoter polymorphisms determined by direct sequencing. Allelic frequency of -238A, -308A, -857T, -863A, and -1031C was 0.6%, 2.2%, 11.1%, 16.7%, and 15.7%, respectively. Association of the gene polymorphisms with a number of variables, because of their high frequency, was analyzed in the latter 3 polymorphisms. There were no significant differences in components of metabolic syndrome and variables affecting atherosclerosis, except in case of serum low-density-lipoprotein cholesterol (LDL-C) (111+/-33 vs 125+/ 39 mg/dl, p<0.05) between -857C/C and -857(C/T+T/T). In contrast, no significant differences were found in these markers between -863C/C and -863(C/A+A/A) and between -1031T/T and -1031(T/C+C/C). Furthermore, 87% of the patients with 857(C/T+T/T) and 64% with -857C/C had carotid plaques (p<0.05). There was no difference in proportion of patients treated with medications such as statins, fibrates, oral hypoglycemic agents, insulin, or antihypertensive drugs between 857C/C and -857(C/T+T/T). These data imply that TNF-alpha gene polymorphism (C 857T) is likely associated with higher serum LDL-C levels and carotid plaque formation in Japanese patients with type 2 diabetes. PMID- 17347551 TI - BCG vaccination enhances resistance to M. tuberculosis infection in guinea pigs fed a low casein diet. AB - In order to examine the relationship between malnutrition and tuberculosis development in vivo, a malnourished guinea pig model fed with a low casein (5%) diet was developed. After being fed with the low casein diet, the guinea pigs were infected with Mycobacterium (M.) tuberculosis Kurono strain by aerosol infection, and seven weeks later were subjected to histopathologic examination, colony-forming unit (CFU) assay, fluorescence-activated cell sorter (FACS) analysis and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL) 12 and inducible nitric oxide synthase (iNOS) mRNA. Another group of guinea pigs were vaccinated subcutaneously with 10(6) CFU BCG Tokyo for three weeks and then similarly infected by aerosol. Eighty-eight% (7/8) of the malnourished guinea pigs succumbed to mycobacterial infection within 85 days after infection, while the malnourished guinea pigs vaccinated with BCG Tokyo survived. CFU assay showed that lung and splenic CFUs were higher in the low casein diet-fed groups than in the control diet (20% casein)-fed groups, although both groups had significantly lower CFUs after vaccination with BCG Tokyo (p<0.01). Examination of lung histopathology revealed that pulmonary granulomas were large and disorganized in the groups fed the low casein diet. The number of visible lesions on the surfaces of the fixed lungs in guinea pigs fed control diet+BCG and low casein diet+BCG was low significantly. Pan T-, CD4-, CD8- and Mac antigen-positive cells were also recognized in the infected lung tissues of low casein-fed guinea pigs and Pan T-, CD4- and Mac antigen-positive cells increased after vaccination with BCG Tokyo. Expression of IFN-gamma, TNF-alpha, IL-12 and iNOS mRNA was also recognized in the infected lung tissues of low casein-fed guinea pigs and IFN gamma and TNF-alpha mRNA expression was enhanced with BCG vaccination. These results indicate that malnutrition exacerbates mycobacterial infection and that malnourished infected hosts may be protected by BCG vaccination. PMID- 17347552 TI - Elevated urinary levels of vitamin D-binding protein in the inhabitants of a cadmium polluted area, Jinzu River basin, Japan. AB - Environmental cadmium (Cd) pollution and its effects on human health are still important issues. The most severe and representative manifestation of chronic Cd intoxication is Itai-itai disease, which is a syndrome that includes renal tubular dysfunction, osteomalacia, and generalized pain due to multiple bone fractures. The whole mechanism of how renal dysfunction relates to the development of bone lesions is unresolved. Vitamin D-binding protein (DBP) binds, transports and activates vitamin D, which plays a major role in calcium homeostasis and bone turnover. In this study, we measured urinary DBP levels and investigated their relationship to the markers of renal tubular dysfunction in the inhabitants of a Cd-polluted Jinzu River basin in Toyama Prefecture, Japan (Cd group). We also investigated age-matched subjects from an area known to have lower levels of Cd pollution (reference group). Urinary DBP was measured by a fluorometric enzyme-linked immunosorbent assay (ELISA), which was established in our laboratory. Significantly higher levels of urinary DBP were observed in the Cd group compared to the reference group. We observed significant positive correlations between urinary levels of DBP and renal tubular dysfunction markers in both groups. In the Cd group, urinary levels of DBP had a negative correlation with serum phosphate value. These results indicate that excretion of urinary DBP is increased after long-term Cd exposure and that the loss of DBP in urine may be linked to renal tubular dysfunction and possibly bone lesions in the inhabitants of Cd-polluted areas. PMID- 17347553 TI - The selective cyclooxygenase-2 inhibitor celecoxib reduces bone resorption, but not bone formation, in ovariectomized mice in vivo. AB - Suppression of increased bone resorption is an important issue in treatment of post-menopausal osteoporosis. Celecoxib is a highly selective inhibitor of cyclooxygenase-2 (COX-2), and inhibits osteoclastogenesis in vitro. In the present study, to test whether celecoxib can suppress elevated bone resorption caused by estrogen deficiency in vivo, celecoxib (4 mg/kg) or its vehicle was administered to sham-operated or ovariectomized (OVX) mice (model of post menopausal osteoporosis). The treatment with celecoxib or vehicle was started immediately after the sham operation or ovariectomy, and lasted for 4 weeks. At 2 and 4 weeks after surgery, OVX mice administered vehicle had significantly higher levels of C-telopeptide, a marker of bone resorption in serum, than sham-operated mice administered vehicle (37% and 60% higher, respectively; p<0.01). At 2 and 4 weeks after surgery, celecoxib treatment significantly decreased serum C telopeptide levels in OVX mice, but not in sham-operated mice (45% and 41%, respectively; p<0.001). In contrast, in both sham-operated and OVX mice, celecoxib did not significantly affect serum osteocalcin levels (a marker of bone formation) or bone mineral density (BMD) of the femur, which was evaluated by peripheral quantitative computed tomography (pQCT). In conclusion, treating OVX mice with celecoxib significantly suppressed the increase in serum levels of the bone resorption marker, but did not affect levels of the bone formation marker. Also, celecoxib did not prevent the decrease of femoral BMD in OVX mice. The present study suggests the possibility that celecoxib may be used to prevent bone loss caused by estrogen deficiency. PMID- 17347554 TI - Pseudolithiasis due to ceftriaxone treatment for meningitis in children: report of 8 cases. AB - Cholelithiasis rarely occurs in childhood. Ceftriaxone is a widely used antimicrobial agent in pediatrics due to the broad spectrum. Reversible biliary sludge and/or lithiasis, named as pseudolithiasis, have been reported in patients treated with ceftriaxone. We observed ceftriaxone-associated pseudolithiasis in 8 patients with meningitis. The aim of this study was to report the clinical characteristics of these patients and to evaluate the related factors for the development of ceftriaxone-associated pseudolithiasis in children. The study group consisted of 7 boys and 1 girl. All patients received ceftriaxone 100 mg/kg/day for meningitis. The ultrasonographic evaluation was performed on 5th 10th days after the initiation of the therapy. Biliary sludge was detected in one patient, and gallstone was detected in three patients, while biliary sludge with gallstone was detected in four patients. Six of the cases were diagnosed during summer time. Thus, high temperature may cause loss of fluid, leading to easier formation of sludge. Ceftriaxone treatment was discontinued after sonographic demonstration of pseudolithiasis. Gallbladder sonograms were found to be normal in all patients at the follow-up sonographic examinations performed after 30 days of the diagnosis without specific treatment. Clinicians should screen all pediatric patients living in areas with high temperature and receiving ceftriaxone treatment (over 100 mg/kg) by ultrasonography for biliary sludge or gallstone formation even if they are asymptomatic. PMID- 17347555 TI - Efficacy of tonsillectomy plus methylprednisolone pulse therapy for a child with Henoch-Schoenlein purpura nephritis. AB - Henoch-Schoenlein purpura (HSP) is a systemic disorder characterized by a leukocytoplastic vasculitis involving small vessels with the deposition of immunoglobulin A (IgA) immune complexes. Renal involvement is the principal cause of morbidity and mortality in children with HSP. We report here an 11-year-old boy with Henoch-Schoenlein purpura nephritis (HSPN) accompanied by recurrent purpura and persistent nephropathy despite conventional therapy such as prednisolone, methylprednisolone pulse therapy and immunosuppressive agent (Mizoribine). The patient was treated with tonsillectomy plus methylprednisolone pulse therapy. This treatment decreased proteinuria, induced disappearance of microscopic hematuria, and improved renal pathological findings. Tonsillectomy plus methylprednisolone pulse is effective and useful therapy for some children with recurrent purpura and persistent nephropathy. PMID- 17347556 TI - The importance of postoperative radiotherapy against polymorphous low-grade adenocarcinoma of the parotid gland: case report and review of the literature. AB - Polymorphous low-grade adenocarcinoma (PLGA) of the salivary gland is a disease entity that is a recently described form of adenocarcinoma. PLGA most commonly arises in the minor salivary glands. We report two cases of PLGA of the parotid gland. Case 1: A 52-year-old female visited the University of Tsukuba Hospital with a painless mass in the left parotid region. A superficial parotidectomy and postoperative radiotherapy were performed. The patient has been free from disease for 50 months. Case 2: A 55-year-old female initially noticed a painless slowly growing mass in the left parotid region. The tumor was removed with a superficial parotidectomy. The local recurrence was found 6 years after the initial surgery. The recurrent tumor was removed, and radiotherapy was administered thereafter. The patient has been free from the disease for 33 months since the last treatment. The treatment for the primary lesion is crucial for the prognosis since metastasis to the regional lymph node or to distant region is unusual in PLGA. Although surgical extirpation is the recommended modality for treatment of PLGA, wide resection with a safety margin is often difficult in the parotid gland because of the presence of the facial nerve. Our two cases were successfully treated with surgery and postoperative radiotherapy. Although our literature search revealed 32 previously reported cases of PLGA of the parotid gland, only five of the 32 cases were treated postoperative radiotherapy. We highlight the importance of postoperative radiotherapy for PLGA of the parotid gland. PMID- 17347557 TI - Neonatal-onset brainstem reticular reflex myoclonus following a prenatal brain insult: generalized myoclonic jerk and a brainstem lesion. AB - Brainstem reticular reflex myoclonus (BRRM) is characterized by sudden, generalized, shock-like movements that can be elicited by sensory stimulation. We present a boy, born after 35 weeks gestation, who was diagnosed with neonatal onset BRRM. Within 1 hr of birth, the patient showed spasticity and generalized clonic movements of all limbs elicited with tactile stimulation anywhere on the body. Surface electromyography showed co-contraction of agonistic and antagonistic muscles, revealing that his generalized clonic movements were tremulous myoclonus in nature. Brain magnetic resonance imaging (MRI) at 21 hrs after birth disclosed high-intensity lesions in the Rolandic area, thalamus, basal ganglia, and brainstem, including the dorsal pons and medulla, the center of BRRM, in T1-weighted images. Follow-up MRI at 1 month revealed dramatic improvement in the pontine lesion. The patient showed gradual remission of the characteristic movements, which disappeared at 1 year of age, but the patient died unexpectedly at 1 year and 3 months. In conclusion, neonatal BRRM arises as a result of severe brainstem injury, and the associated lesions may only be seen temporarily on MRI taken soon after birth. PMID- 17347558 TI - Chitotriosidase activity in the serum of patients with sarcoidosis and pulmonary tuberculosis. AB - BACKGROUND: Human chitotriosidase is a chitinase selectively expressed by activated macrophages. An increase in chitotriosidase activity was previously described by us in the serum and bronchoalveolar lavage of sarcoidosis patients. OBJECTIVE: The aim of the present study was to analyze serum chitotriosidase activity in a larger number of sarcoidosis patients to verify the reported increase with respect to controls and to compare serum chitotriosidase levels in patients with sarcoidosis and tuberculosis, two granulomatous disorders of different etiology. METHODS: Chitotriosidase activity was measured in the serum of 96 sarcoidosis patients, 15 pulmonary tuberculosis patients and 30 healthy controls. RESULTS: We found significantly higher serum chitotriosidase activity in sarcoidosis patients than controls (p < 0.01) and in sarcoidosis patients than tuberculosis patients (p < 0.01), confirming a striking elevation of chitotriosidase activity (>10 times greater than normal) in pulmonary sarcoidosis patients. This is the first time that chitotriosidase activity has been analyzed in the serum of patients with pulmonary tuberculosis; it was found to be significantly lower than in sarcoidosis patients and not significantly greater than in controls. CONCLUSION: Although the mechanisms leading to the increase in chitotriosidase activity in sarcoidosis are still unknown, this enzyme may be specifically involved in the pathogenesis of the disease. Further studies with a greater number of patients are needed to confirm these results and to determine whether chitotriosidase could be a marker with diagnostic or prognostic value in sarcoidosis. PMID- 17347559 TI - Autonomic neuropathy increases the risk of obstructive sleep apnea in obese diabetics. AB - BACKGROUND: Nonobese diabetics with diabetic autonomic neuropathy (DAN) show an elevated prevalence of obstructive sleep apnea-hypopnea (OSAH). OBJECTIVE: It was the aim of this study to assess if the presence of DAN could further increase the risk of developing OSAH in obese diabetics. METHODS: Eighteen obese diabetic patients, 8 with DAN [age 57 +/- 5 years, body mass index (BMI) 35 +/- 4] and 10 without DAN (age 56 +/- 8 years, BMI 37 +/- 5), were recruited. Ten age-matched obese subjects were studied as controls (age 53 +/- 12 years, BMI 34 +/- 3). All subjects underwent a cardiorespiratory sleep study in the in-hospital sleep laboratory to obtain the apnea-hypopnea index (AHI) and oxygen desaturation indices. RESULTS: Diabetics with DAN (Ob-DAN+) had a higher AHI than diabetics without DAN (Ob-DAN-) and controls, amounting to 39.5 +/- 13 versus 15.8 +/- 12 (p < 0.01) and 19.3 +/- 21 (p < 0.05), respectively. A moderate-to-severe OSAH (AHI > or = 15) occurred in all Ob-DAN+ and only in 4 Ob-DAN- and 4 control patients. Moreover, the indices reflecting the impairment of oxygen saturation (SaO(2)) during sleep such as the mean lowest SaO(2) and sleep time with a SaO(2) <90% were more severely affected in Ob-DAN+ patients compared with the other groups and were associated with longer obstructive respiratory events. CONCLUSIONS: Apneas-hypopneas are more frequent and last longer in Ob-DAN+ than in other obese subjects, with or without diabetes. PMID- 17347560 TI - Arkadia-Smad7-mediated positive regulation of TGF-beta signaling in a rat model of tubulointerstitial fibrosis. AB - BACKGROUND/AIMS: Upregulation of transforming growth factor beta (TGF-beta)/Smad signaling has been implicated in the primary pathogenesis of renal fibrosis. The ubiquitin-proteasome pathway has an important influence on TGF-beta signaling through regulating Smad degradation. As E3 ubiquitin ligases, both Arkadia and Smurf2 are involved in this prosess. In this study, we focused on Arkadia, Smurf2, Smad7, and TGF-beta type I receptor (TbetaRI), principal molecules in the regulation of TGF-beta signaling, to understand the regulatory mechanism of ubiquitin-proteasomal degradation of TGF-beta signaling in the pathogenesis of renal fibrosis. METHODS: A unilateral ureteral obstruction (UUO) model was employed, and sham-operated rats were used as controls. Renal lesions and the expression of Arkadia, Smurf2, Smad7, TbetaRI, TGF-beta1, and type 1 collagen (COL-1) were detected by Western blot, immunoprecipitation, immunohistochemistry, and/or reverse transcription-polymerase chain reaction. RESULTS: The results indicated progressive tubulointerstitial fibrosis, high expression levels of Arkadia, Smurf2, TbetaRI, TGF-beta1 mRNA, type 1 collagen mRNA, and Smad7 mRNA, and low levels of Smad7 protein in the kidneys of rats with unilateral ureteral obstruction, in which Smurf2 interacted with both Smad7 and TbetaRI, and Arkadia only interacted with Samd7 but not with TbetaRI. CONCLUSION: Reduction of Smad7 resulting from ubiquitin-dependent degradation may be mainly attributed to Arkadia, and Arkadia-Smad7-mediated positive regulation of TGF-beta signaling may play a promoting role in the progression of tubulointerstitial fibrosis. PMID- 17347561 TI - Synergistic antitumor activity of oxaliplatin in combination with gemcitabine in pancreatic tumor-bearing mice. AB - Oxaliplatin (OX) and gemcitabine (GEM) are both drugs with proven clinical activity in various tumor types, have no overlapping toxic side effects and are different with respect to cellular metabolism. Therefore, we performed an in vivo study to determine the efficacy of the combination of these two drugs to optimize the scheduling of both substances using pancreatic ductal adenocarcinoma PAN-02, subcutaneously growing in C57Bl mice. A total of 164 mice were used for cytotoxicity and antitumor studies. The combination therapy resulted in better results than those observed when the drugs were administered individually. GEM (58 mg/kg) and OX (1.0 mg/kg) achieved a 52% reduction in tumor size on day 28 after transplantation and a T/C value of 168% when the intermittent treatment schedule on days 1, 4 and 7 after inoculation was used. This treatment schedule was superior to other therapeutic schedules, producing a synergistic antitumor effect much higher than the one expected by the simple addition of the effects by OX and GEM acting independently. PMID- 17347562 TI - Cytotoxicity of diospyrin and its derivatives in relation to the generation of reactive oxygen species in tumour cells in vitro and in vivo. AB - BACKGROUND: Alkyl ethers (D2 and D7) synthesized from diospyrin (D1), a naphthoquinonoid isolated from Diospyros montana Roxb., were evaluated for cytotoxicity and capacity to generate reactive oxygen species (ROS) in tumour cells. METHODS: The tumour inhibitory activity of the quinonoids was assessed in vivo against Ehrlich ascites carcinoma (EAC), while cytotoxicity was determined in vitro on EAC and MCF-7 cancer cells by MTT assay. ROS generated by quinonoids in MCF-7 cells was measured fluorimetrically. RESULTS: The tumour inhibitory activity, cytotoxicity and ROS generation capacity of quinonoids were found to be D7 > D2 > D1. CONCLUSION: Alkyl ethers of D1 were more cytotoxic against tumour cells in vitro as well as in vivo. PMID- 17347563 TI - Vivotif--a 'magic shield' for protection against typhoid fever and delivery of heterologous antigens. AB - The attenuated Salmonella typhi strain Ty21a is the main constituent of Vivotif, the only attenuated live oral vaccine against typhoid fever. In comparison with antibiotics, the 'magic bullets' which Paul Ehrlich was striving for to treat infectious diseases, this vaccine should be viewed as a 'magic shield', because rather than treating typhoid fever after the infection has started, immunisation with this vaccine strain prevents infection and disease by the induction of specific immune responses. Ty21a is also an attractive carrier for the delivery of heterologous antigens. Recently, we successfully used Ty21a for antigen delivery via the haemolysin secretion system of Escherichia coli, which allows efficient protein secretion from the carrier bacteria. PMID- 17347564 TI - Susceptibilities of ESBL-producing Enterobacteriaceae to ertapenem, meropenem and piperacillin-tazobactam with and without clavulanic acid. AB - BACKGROUND: Faced with the extended-spectrum beta-lactamase (ESBL) pandemic, we compared the susceptibilities of ESBL-producing Enterobacteriaceae to ertapenem, meropenem and piperacillin-tazobactam with and without clavulanate. METHODS: 121 strains of Escherichia coli and Klebsiella were studied. 70 strains were originally reported as resistant to ceftazidime based upon disk diffusion; 51 strains were originally reported as sensitive to ceftazidime based upon previous guidelines of the National Committee for Clinical Laboratory Standards, but subsequently shown to be ESBL producers. Minimal inhibitory concentrations (MICs) of the strains towards ertapenem, meropenem and piperacillin-tazobactam were determined by Etest. The effect of adding clavulanate on the MICs was determined by performing the Etest, using plates containing 2 microg/ml of clavulanate. RESULTS: The MIC90 of all isolates was 0.094 and 0.25 microg/ml for ertapenem, 0.032 and 0.064 microg/ml for meropenem, and 16 and 256 microg/ml for piperacillin-tazobactam with and without clavulanate, respectively. CONCLUSIONS: ESBL-producing organisms were more susceptible to meropenem than to ertapenem, although the MICs to ertapenem were well within clinically achievable levels. Piperacillin-tazobactam was ineffective in a large percentage of isolates. The presence of clavulanate resulted in a 5-fold decrease in the MIC of ertapenem and in a drastic reduction in the MIC of piperacillin-tazobactam. The decrease observed with ertapenem is unlikely to be of clinical significance. Thus, in our hospital, ertapenem could be a good meropenem-sparing agent for infections due to ESBL-producing organisms. Piperacillin-tazobactam appeared to be a poor choice, as our isolates produce ESBLs which are not successfully inhibited by tazobactam. PMID- 17347565 TI - Time-kill kinetics of Streptococcus pneumoniae with reduced susceptibility to telithromycin. AB - BACKGROUND: Telithromycin is a new ketolide increasingly used in Europe and the United States. Only very few telithromycin-resistant isolates have been described to date. METHODS: The anti-pneumococcal activity of telithromycin was determined against four clinical isolates of Streptococcus pneumoniae with reduced susceptibility to telithromycin by time-kill methodology. RESULTS: All four telithromycin non-susceptible strains had the constitutive macrolide-lincosamide streptogramin B phenotype and the ermB genotype. Pneumococcal strains had telithromycin minimum inhibitory concentrations (MICs) ranging between 2 and 8 microg/ml. Mulitlocus sequence typing and serotyping showed three isolates to harbour the identical serotype (serotype 14) and sequence type (sequence type 143) indicating a genetic relatedness of strains. Telithromycin was only bactericidal against the isolates with telithromycin resistance, with 4-8 times the MIC after 24 h. CONCLUSION: The killing by telithromycin of S. pneumoniae isolates having an ermB resistance determinant and a telithromycin MIC of > or =2 microg/ml is slow. Achievable concentrations in serum, alveolar macrophages and epithelial lining fluid are below the concentrations which are necessary for bactericidal killing of highly telithromycin-resistant strains. PMID- 17347566 TI - Somatotype in Alzheimer's disease. AB - BACKGROUND: The clinical picture of Alzheimer's disease includes anthropometric and body composition variations. Somatotyping is a practical non-invasive method to assess body type. OBJECTIVE: The objective of this study was to describe the somatotype of a sample of Alzheimer's patients. METHODS: The sample consisted of 55 Alzheimer disease individuals in the mild-moderate stage (17 men, mean age = 76.9 +/- 7.2 years; 38 women, mean age = 79.6 +/- 6.4 years). The pathological subjects were compared with a control group consisting of 280 healthy individuals (134 men, mean age = 74.2 +/- 7.3 years; 146 women, mean age = 74.9 +/- 7.4 years). The Heath-Carter somatotype was applied. RESULTS: The Alzheimer patients (mean somatotype: 6.1-5.5-0.8 in men, 7.0-5.3-0.7 in women) are less mesomorphic and more ectomorphic than the controls (mean somatotype: 6.1-6.3-0.6 in men, 7.7 6.3-0.4 in women), the differences being significant in women (mesomorphy, p = 0.000; ectomorphy, p = 0.012). CONCLUSION: Alzheimer patients show peculiar somatometric characteristics. The somatotype technique could represent a suitable tool for the study and monitoring of physical variations. PMID- 17347567 TI - Urinary incontinence in disabled elderly women: a randomized clinical trial on the effect of training mobility and toileting skills to achieve independent toileting. AB - BACKGROUND: Urinary incontinence is very prevalent in elderly women, and it is considered a major burden for both patient and caregiver. OBJECTIVE: To determine feasibility and effect of training mobility and toileting skills on the severity of urinary incontinence in elderly, dependent women. METHODS: In a randomized, single-blinded trial, 57 dependent, nondemented, elderly women with long-standing urinary incontinence and a mild to moderate disorder in mobility and transfers were recruited in 24 long-term care institutions. The participants were randomized to receive either no treatment (n = 28) or an individualized 8-week training program of mobility and toileting skills (n = 29), provided by physiotherapists and/or occupational therapists. RESULTS: The intervention resulted in a 37.7% reduction in the daily amount of urine loss. Three women in the intervention group compared to none in the control group became continent. A change from dependent to independent toileting occurred in 6 women in the intervention group and in 2 women in the control group. All these results, however, were not statistically significant. The intervention did have a significant effect on the daytime sum score of the toilet timing test. CONCLUSIONS: This study suggests that it is possible to influence long-standing incontinence in dependent elderly women by training mobility and toileting skills. Future studies should have a larger sample size, and more attention should be paid to the motivation of the participants. PMID- 17347568 TI - The LOC387715 gene, smoking, body mass index, environmental associations with advanced age-related macular degeneration. AB - BACKGROUND AND AIMS: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western World. It is now evident that both genetic and environmental factors contribute to disease susceptibility. We tested the hypotheses that (a) a common coding SNP in the LOC387715 gene is associated with advanced AMD (geographic atrophy or choroidal neovascularization), and (b) that modifiable environmental exposures alter AMD susceptibility associated with this SNP. METHODS: A case-control association analysis was performed on participants (530 advanced AMD cases and 280 controls) ascertained as part of the multi-center Age-Related Eye Disease Study. AMD status was determined by the reading center from fundus photographs using the AREDS AMD grading categorization. Environmental risk factor exposure data was collected from participants whose DNA was also genotyped for the LOC387715 gene SNP rs10490924. Multivariate logistic regression analyses were performed. RESULTS AND CONCLUSIONS: The number of risk alleles at the LOC387715 SNP was associated with advanced AMD, with odds ratios (OR) = 3.0 (95% confidence interval (CI) 2.1-4.3) for the GT heterozygous genotype and OR = 12.1 (5.6-26.5) for the homozygous TT risk genotype, after controlling for demographic and behavioral risk factors. The LOC387715 SNP was associated with both forms of advanced AMD. Current cigarette smoking and body mass index were independently related to AMD, controlling for genotype. However, there was no statistical interaction between LOC387715 genotype and smoking with regard to advanced AMD development. PMID- 17347569 TI - Differential dropout among SNP genotypes and impacts on association tests. AB - BACKGROUND: Current biotechnologies are able to achieve high accuracy and call rates. Concerns are raised on how differential performance on various genotypes may bias association tests. Quantitatively, we define differential dropout rate as the ratio of no-call rate among heterozygotes and homozygotes. METHODS: The hazard ofdifferential dropout is examined for population- and family-based association tests through a simulation study. Also, we investigate detection approaches such as Hardy-Weinberg Equilibrium (HWE) and testing for correlation between sample call rate and sample heterozygosity. Finally, we analyze two public datasets and evaluate the magnitudes of differential dropout. RESULTS: In case-control settings, differential dropout has negligible effect on power and odds ratio (OR) estimation. However, the impact on family-based tests range from minor to severe depending on the disease parameters. Such impact is more prominent when disease allele frequency is relatively low (e.g., 5%), where a differential dropout rate of 2.5 can dramatically bias OR estimation and reduce power even at a decent 98% overall call rate and moderate effect size (e.g., OR(true) = 2.11). Both of the two public datasets follow HWE; however, HapMap data carries detectable differential dropout that may endanger family-based studies. CONCLUSIONS: Case-control approach appears to be robust to differential dropout; however, family-based association tests can be heavily biased. Both of the public genotype data show high call rate, but differential dropout is detected in HapMap data. We suggest researchers carefully control this potential confounder even using data of high accuracy and high overall call rate. PMID- 17347570 TI - Dealing with missing data in family-based association studies: a multiple imputation approach. AB - To test for association between a disease and a set of linked markers, or to estimate relative risks of disease, several different methods have been developed. Many methods for family data require that individuals be genotyped at the full set of markers and that phase can be reconstructed. Individuals with missing data are excluded from the analysis. This can result in an important decrease in sample size and a loss of information. A possible solution to this problem is to use missing-data likelihood methods. We propose an alternative approach, namely the use of multiple imputation. Briefly, this method consists in estimating from the available data all possible phased genotypes and their respective posterior probabilities. These posterior probabilities are then used to generate replicate imputed data sets via a data augmentation algorithm. We performed simulations to test the efficiency of this approach for case/parent trio data and we found that the multiple imputation procedure generally gave unbiased parameter estimates with correct type 1 error and confidence interval coverage. Multiple imputation had some advantages over missing data likelihood methods with regards to ease of use and model flexibility. Multiple imputation methods represent promising tools in the search for disease susceptibility variants. PMID- 17347571 TI - Relationship between nocturnal growth hormone concentrations, serum IGF-I/IGFBP-3 levels, insulin sensitivity and GH receptor allelic variant in small for gestational age children. AB - Growth hormone may help to increase final height in patients with short stature, but its efficacy is variable. It has been recently reported that the isoform of the GH receptor (GHR) that lacks exon 3 (d3-GHR) is associated with a greater growth response to GH therapy. We hypothesized that nocturnal growth hormone concentrations, basal IGF-I and IGFBP-3 levels, and insulin sensitivity might show variations among individuals depending on their GHR allelic variant. To test this hypothesis, we studied 38 prepubertal LBW children with nocturnal GH concentrations, IGF-I and IGFBP-3 levels and insulin sensitivity during OGTT and Insulin test. The GHR allelic variant was analyzed through multiplex PCR analysis in DNA from peripheral leukocytes. Characteristics of the overnight GH secretion [(mean GH: 6.8 +/- 0.6 vs. 6.2 +/- 0.5 ng/ml), (AUC: 3,227 +/- 280 vs. 2,908 +/- 212 ng/ml.min), (peak number: 4.4 +/- 0.3 vs. 4.4 +/- 0.2), (amplitude: 12 +/- 1.1 vs. 10.8 +/- 1.1 ng/ml)] did not differ between groups (f1/f1 vs. f1/d3 plus d3/d3). In addition, we did not observe any significant differences in serum IGF I SDS (-0.49 +/- 0.26 vs. -0.40 +/- 0.35) or IGFBP-3 SDS (-1.21 +/- 0.24 vs. 0.89 +/- 0.21) nor in insulin sensitivity (WIBSI: 12 +/- 1.2 vs. 10.8 +/- 1.1) in LBW children with full length GHR compared to children carrying at least one GHRd3 allele. The distribution of the f1/f1 allelic variant and fi/d3 or d3/d3 was similar in the LBW children with or without catch-up growth. These results suggest that the GHR allelic variant does not play a significant role in the regulation of GH-IGF-I/BP3 axis or in insulin sensitivity in prepubertal LBW children. PMID- 17347572 TI - Generation of allergen-enriched protein fractions of Hevea brasiliensis latex for in vitro and in vivo diagnosis. AB - BACKGROUND: The latex of Hevea brasiliensis trees contains a complex proteome that includes a range of allergenic proteins. Current latex extracts that are used for the diagnosis of latex allergy still lack important allergens. We aimed to devise a production process for an improved reagent that would ideally contain the complete latex allergome. METHODS: Latex C-serum was fractionated by ammonium sulfate precipitation, and B- and C-serum proteins were then separated by anion exchange chromatography. Proteins eluting within defined salt concentration ranges were pooled into six final fractions. Fractions were evaluated by two dimensional electrophoresis and subsequent IgE immunoblot for their spectrum of allergens. The presence of the most important latex allergens in the fractions was checked by Western blot analyses. Each fraction was further evaluated by skin prick test (SPT). RESULTS: Reproducibility of the preparation method was demonstrated with two batches of latex. Comparison of latex B- and C-serum to the six fractions showed a remarkable increase in the number of detectable allergens in the fractions. The presence of the latex allergens Hev b 1-8 and Hev b 13 in the fractions was demonstrated. In SPTs, the fractions produced wheal-and-flare reactions comparable to commercial latex extracts. CONCLUSIONS: This method provides reproducible latex protein fractions of high allergen content for the diagnosis of latex allergy. PMID- 17347573 TI - Age-related difference in the persistency of allergic airway inflammation and bronchial hyperresponsiveness in a murine model of asthma. AB - AIM: Asthmatic children are more likely to outgrow their symptoms than adult patients. Thus, we wanted to know whether there were any age-related differences in the time course of the allergic airway inflammation. METHODS: BALB/C mice at different ages (young: 3 days after birth, and mature: 8 weeks of age) were sensitized with ovalbumin (OVA). Subsequently, animals were challenged with aerosolized OVA during 1, 2, 4 or 8 consecutive weeks. Bronchial hyperresponsiveness (BHR), serum IgE levels, the degrees of inflammatory cell infiltration (ICI) and goblet cell metaplasia (GCM) in the airways, and the number of eosinophils and cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. RESULTS: At 1 week, airway inflammation and BHR occurred similarly between young and mature mice. However, BHR disappeared at 4 weeks in young, whereas it persisted even at 8 weeks in mature mice. GCM, ICI and eosinophilia in BALF attenuated with time, with more remarkable reduction in young mice. The BALF IL-4 level was high during the first 2 weeks in both groups, while the IL-2 level was significantly increased at 2 weeks solely in young mice. CONCLUSION: Different time courses in airway inflammation and in BHR may relate to the different prognoses between childhood and adult asthma. The understanding of the mechanisms underlying this age-related differences may be helpful to induce remission in asthmatic patients. PMID- 17347574 TI - Unexpected phenotype of STAT6 heterozygous mice implies distinct STAT6 dosage requirements for different IL-4 functions. AB - BACKGROUND: STAT6 is an important transcription factor in interleukin-4 (IL-4) signaling, a key cytokine in atopic diseases and allergic asthma. STAT6 gene targeted mice are unable to develop IgE and T helper 2 cell (Th2) responses in several models of allergic and infectious diseases. In experiments to further elucidate STAT6 functions in vivo, we unexpectedly observed severely impaired IL 4 functions in STAT6 heterozygous (STAT6+/-) mice which were further analyzed in this study. METHODS: BALB/c mice, either wild-type (STAT6+/+), STAT6 heterozygous (STAT6+/-) or STAT6 deficient (STAT6-/-), were analyzed for their ability to mount an IL-4-induced IgE response in vitro and in vivo. Supernatants of stimulated B cells and sera of Leishmania major-infected mice were analyzed for IgE, IgG1 and IgG2a concentrations by ELISA. Transcripts accompanying IgE class switching were amplified by RT-PCR and the expression of CD23 and MHC class II molecules on B cells was assessed by FACS analysis. RESULTS: B cells from STAT6+/ mice were unable to secrete IgE in vitro and in vivo and transcripts accompanying IgE class switching were drastically reduced, whereas IL-4-induced upregulation of MHC class II was unimpaired and CD23 expression levels were only slightly affected. Additionally, STAT6+/- mice were equally resistant to infection with L. major as STAT6-deficient (STAT6-/-) mice, due to a defect in mounting a Th2-dominated immune response. CONCLUSION: Different STAT6-dependent IL-4 functions require different thresholds of activated STAT6 molecules. PMID- 17347575 TI - Association between mild renal dysfunction and insulin resistance or metabolic syndrome in a random nondiabetic population sample. AB - AIMS: The association of mild renal dysfunction (estimated glomerular filtration rate [eGFR] 60-89.9 ml/min/1.73 m(2)) with insulin resistance (IR) or metabolic syndrome (MS) needs be investigated in a population in which MS prevails. METHODS: After excluding subjects with diabetes mellitus, 1,678 subjects from a representative cohort (median age 52 years) were studied cross-sectionally. eGFR was based on serum creatinine concentrations using the quadratic GFR equation and categorized by 90 and 60 ml/min/1.73 m(2) as limits. MS was identified using the modified criteria of the Adult Treatment Panel-III. RESULTS: In men, whereas MS was not significantly associated with a reduced eGFR category when controlled for homeostatic model assessment (HOMA), HOMA adjusted for MS or for its components was significantly associated with the likelihood of a reduced eGFR. This likelihood was increased by 14% with a doubling of HOMA in men. Age was the dominant correlate of reduced eGFR in women, whereby an association with HOMA was not significant. CONCLUSION: Mildly impaired kidney function is common in nondiabetic adults among whom MS prevails, and in men it is mainly associated with IR but not with central obesity and MS-related dyslipidemia. The quadratic GFR equation enables an acceptable estimation of GFR in a general population. PMID- 17347576 TI - Relationship between glomerular filtration rate and the prevalence of metabolic abnormalities: results from the Third National Health and Nutrition Examination Survey (NHANES III). AB - BACKGROUND AND AIMS: National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend that all people with a glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) undergo evaluation for anaemia and metabolic bone disease. We aim to report the prevalence of metabolic complications in adults with low GFR. METHODS: Analysis of 15,802 non institutionalised adult participants in the Third National Health and Nutrition Survey (NHANES III), a cross-sectional population-based survey conducted in the United States between 1986 and 1994. Renal function was estimated according the modification of diet in renal disease equation 7 (MDRD GFR), the Cockcroft-Gault formula and by the serum creatinine cut-off points described by Couchoud and colleagues. Haemoglobin <110 g/l occurred in 42.2% [95% confidence interval (CI) 28.3-56.0] of patients with MDRD GFR <30 ml/min/1.73 m(2) [stage 3 chronic kidney disease (CKD)] and 3.5% (95% CI 2.4-4.7) of patients with MDRD GFR between 30 and 60 ml/min/1.73 m(2) (stage 4-5 CKD). Corresponding prevalences for calcium <2.15 mmol/l were 8.2 (95% CI 1.6-14.8) and 3.4 (95% CI 1.7-5.2); for phosphate >1.6 mmol/l, 15.1 (95% CI 5.0-25.3) and 0.3 (95% CI 0-0.6); and for bicarbonate <23 mmol/l, 32.7 (95% CI 19.6-45.9) and 5.7 (95% CI 3.3-8.2), respectively. Similar results were obtained when patients were categorised by the Cockcroft-Gault formula or Couchoud's cut-off points. CONCLUSIONS: The prevalence of complications in stage 3 CKD is low. These data do not support the recommendation for routine screening for metabolic complications of renal insufficiency in adults seen in primary care settings whose GFR exceeds 30 ml/min/1.73 m(2). PMID- 17347577 TI - Effect of two different dialysis membranes on leukocyte adhesion and aggregation. AB - AIMS: We evaluated modifications in formation of heterotypic platelet-leukocyte aggregation induced by dialysis through cellulosic or synthetic membranes and evaluated the effects of such procedures promoting adhesive interactions between leukocytes and normal endothelial cells (ECs). METHODS: Samples were obtained from arterial and venous lines at baseline, after 15 and 120 min of hemodialysis. Heterotypic aggregation was assessed using flow-cytometric techniques. Experiments to determine leukocyte adhesion to ECs were performed in parallel plate perfusion chambers at 450 s(-1). RESULTS: Patients dialyzed with a cellulosic membrane showed a significantly higher baseline granulocyte heterotypic aggregation (median 22.5%, range 8.6-32%) versus healthy subjects (median 10%, range 3.2-14.6%; p < 0.05). Granulocyte heterotypic aggregation values remained increased throughout the hemodialysis session not only in the arterial line (median 18 and 24.5%, range 7-30 and 8.7-36% at 15 and 2 h, respectively) but also in the venous line (median 20 and 25%, range 8.6-32 and 11.5-35% at 15 min and 2 h, respectively). Basal lymphocytes heterotypic aggregation values observed in uremic patients were 6% (0.1-7.1%) versus 1.0% (0.5-2.8%) in the control group (p < 0.05). The increase remained during the hemodialysis session both in the arterial line (median 5 and 4%, range 0.2-14 and 0.5-7.1 % at 15 min and 2 h, respectively) and in the venous line (median 7 and 7%, range 1.4-14 and 0.5-10.6% at 15 min and 2 h). In contrast, patients dialyzed with a synthetic membrane showed a decreased basal granulocyte heterotypic aggregation compared to healthy subjects (median 3.5 vs. 10%, range 2.8-7 vs. 3.2 14.6%, respectively; p < 0.05). For lymphocytes, basal heterotypic aggregation values were 0.2% (range 0.1-0.5%) in dialyzed patients vs. 0.98% (range 0.5-2.8%) in healthy subjects (p < 0.05), without changes throughout the dialysis session. Changes in leukocyte adhesion during hemodialysis did not reach statistical significance with either hemodialysis membrane. Our studies confirm a differential activation of platelets and leukocytes depending on the nature of the dialysis membranes. However, activation of circulating cellular elements by hemodialysis procedures did not enhance cross-talk interactions between leukocytes and unaltered ECs. PMID- 17347578 TI - Implications of levels of serum mineral metabolism markers, albumin and C reactive protein for treatment costs of patients on maintenance dialysis. AB - BACKGROUND: Secondary hyperparathyroidism, malnutrition and inflammation have been reported to associate with adverse outcomes in dialysis patients. However, little is known about the implications of these conditions for treatment costs. METHODS: The cost data of all adult patients who had entered dialysis therapy at Tampere University Hospital between 1991 and 1996 and had remained on dialysis for at least 1 year were collected. results of measurements of parathyroid hormone (PTH), calcium, phosphorus, albumin and C-reactive protein (CRP) were obtained from the database of the hospital. RESULTS: Patients (n = 109), aged 57.0 +/- 14.9 years, included 57% men and 37% diabetics; 62% started on hemodialysis and 38% on peritoneal dialysis. Average daily costs were USD 161 (range 95-360). After controlling for patients' age, body mass index, gender, dialysis modality and primary renal disease, there was a positive correlation between average CRP and average costs and a negative correlation between albumin and costs. Correlations between mineral metabolism markers and costs were not found, but there was a trend towards lower cost among patients who achieved the Kidney Disease Outcomes Quality Initiative targets of calcium, phosphorus and PTH (USD 145 +/- 31) compared with those with nonoptimal levels (USD 165 +/- 48; p = 0.095). Costs of patients with at least one in-target PTH measurement were lower than costs of patients with constantly low PTH (USD 148 +/- 31 vs. 170 +/- 48; p = 0.01). CONCLUSION: Serum levels of albumin and CRP correlated with dialysis patients' treatment costs. Achieving the Kidney Disease Outcomes Quality Initiative targets may be associated with lower costs. PMID- 17347579 TI - Reduction in platelet activation by citrate anticoagulation does not prevent intradialytic hemodynamic instability. AB - BACKGROUND: The etiology of intradialytic hemodynamic instability is multifactorial. Of the various factors involved, a rise in core temperature seems to be crucial. In this respect, the bioincompatibility of hemodialysis (HD) treatment might play an important role. The application of cool dialysate reduces the number of periods of intradialytic hypotension (IDH) considerably. In rats, roller pump perfusion caused hypotension by shear stress induced platelet aggregation and subsequent serotonin release. During clinical HD, citrate anticoagulation abolished platelet activation almost completely. Hence, citrate anticoagulation might reduce IDH, whereas the beneficial effect of cool dialysate might be partly explained by reduced platelet activation. METHODS: In the present study, blood pressure, IDH episodes, platelet activation, platelet aggregation, and serotonin release were studied crossover in 10 patients during HD with dalteparin anticoagulation at normal and low dialysate temperatures and during HD with citrate. RESULTS: Citrate strongly reduced platelet activation, but did not improve IDH. The blood pressure was best preserved during cool-temperature HD, despite manifest platelet activation. Platelet activation was not accompanied by a rise in the plasma serotonin concentration. CONCLUSIONS: Three major conclusions can be drawn: (1) it is unlikely that platelet activation and subsequent serotonin release underlie IDH in the clinical situation; (2) the protective effects of cool dialysate on IDH appear to be independent of HD induced platelet activation, and (3) extrapolating results from rat experiments to the human situation requires uppermost prudence. PMID- 17347580 TI - The TGFbeta1-induced fibronectin in human renal proximal tubular epithelial cells is p38 MAP kinase dependent and Smad independent. AB - BACKGROUND/AIM: Transforming growth factor beta 1 (TGFbeta1) is a fibrokine implicated in the progression of renal fibrosis. Following TGFbeta1 receptor activation, a number of signalling pathways are stimulated. This study investigates the role of p38 mitogen-activated protein (MAP) kinase and Smad pathways in the TGFbeta1-induced fibronectin (FN) production. METHODS: Transformed human proximal tubular epithelial cells of the line HKC were used. Secreted FN was analyzed by enzyme-linked immunosorbent assay and Smad proteins by Western blotting. Chemical inhibitors were used to study the role of p38 MAP kinase and the TGFbeta receptor ALK5. The Smad pathway was studied using a cell line overexpressing Smad7 and small interfering RNAs (siRNA). The FN mRNA expression was assessed by reverse transcription-polymerase chain reaction. RESULTS: TGFbeta1 produced a significant increase in FN secretion in both HKC and Smad7-HKC cells, and the p38 MAP kinase inhibitor SB202190 markedly reduced this (n = 3, p < 0.05 and p < 0.01). ALK5 inhibition also reduced the TGFbeta1-induced FN (n = 3, p < 0.05). Smad knockdown using the siRNA did not reduce the TGFbeta1 induced FN secretion. TGFbeta1 induced FN mRNA expression in HKC cells, and SB202190 decreased this induction (n = 5, p < 0.05). CONCLUSIONS: These results suggest that TGFbeta1-induced FN production in HKC cells is p38 MAP kinase dependent and Smad independent. Targeting p38 MAP kinase may be of therapeutic value in renal fibrosis. PMID- 17347581 TI - Enhanced expression of ANGPTL2 in the microvascular lesions of diabetic glomerulopathy. AB - BACKGROUND: Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes mellitus. However, the underlying mechanisms remain unclear. We studied the expression characteristics of angiopoietin-like 2 (ANGPTL2), a novel DN-associated growth factor identified in our previous gene chip screening. METHODS: Glomeruli were microdissected from renal biopsies from 24 patients with DN and 8 donor controls. The expression of ANGPTL2 was assessed by RT-PCR and immunohistochemistry, and then correlated with clinical and pathological indices of glomerular injury. RESULTS: Consistent with the results of the gene chip experiment, abundant expression of ANGPTL2 was found more frequently in diabetic glomeruli as compared to donor controls (95 vs. 38%, chi(2) = 15.9, p < 0.01). ANGPTL2 mRNA upregulation was more prominent in glomeruli with less microaneurysm (22 vs. 66%, p < 0.05), inflammatory influx (6 vs. 50%, p < 0.05) or endothelial foam cell formation (11 vs. 53%, p < 0.05). Immunostaining revealed an upregulation of ANGPTL2 protein in hypertrophied diabetic glomeruli, mainly distributed in podocytes, which were supposed to be the origin of ANGPTL2. CONCLUSION: The upregulation of ANGPTL2 in diabetic glomerulopathy shows a close relationship to abnormal microvasculature and endothelial inflammation. ANGPTL2 may play an important role in the pathogenesis of diabetic glomerulopathy. PMID- 17347582 TI - The combination of ACE inhibition plus sympathetic denervation is superior to ACE inhibitor monotherapy in the rat renal ablation model. AB - BACKGROUND: The blood pressure-independent renoprotective actions of the blockade of the renin-angiotensin and the sympathetic nervous system are well documented, but monotherapies fail to completely abrogate progression. We investigated whether combined inhibition of the two systems provides additive renoprotection. METHODS: After subtotal nephrectomy (SNX) or sham operation, rats underwent resection of dorsal roots, i.e. rhizotomy or sham rhizotomy. Subsequently, they received tap water or quinapril in drinking water for 16 weeks (n = 18/group). Albuminuria, blood pressure and kidneys were assessed (morphometry, immunohistochemistry). RESULTS: At the end of the study telemetric blood pressure in SNX was 118 +/- 16 mm Hg, in SNX + rhizotomy 110 +/- 10 mm Hg, in SNX + quinapril 103 +/- 9 mm Hg and in SNX + quinapril + rhizotomy 95 +/- 7 mm Hg. Albuminuria in the respective groups was 169 +/- 75, 86 +/- 45, 15 +/- 23 and 5 +/- 4 mg/24 h. The glomerulosclerosis index was 1.40 +/- 0.6, 0.80 +/- 0.23, 0.37 +/- 0.16 and 0.31 +/- 0.15 (p < 0.001). Only combined intervention caused significant reduction of the glomerular volume and podocyte hypertrophy. The lowest indices for nitrotyrosine, NOS-1 (nNOS), TGF-beta and interstitial collagen were seen with combined interventions (p < 0.05). CONCLUSION: In angiotensin-converting enzyme inhibitor-treated SNX animals, abrogation of sympathetic overactivity provides additional renoprotection and less nitro oxidative stress of podocytes than single interventions. The added benefits were partially blood pressure independent. PMID- 17347583 TI - Various dietary protein intakes and progression of renal failure in spontaneously hypercholesterolemic Imai rats. AB - BACKGROUND/AIM: Dietary protein restriction is known to be beneficial in the preservation of the renal function in patients with chronic renal failure. Recently, the effect of varying quantity and quality of dietary protein intakes was also studied. This study investigates the effects of different dietary animal proteins on renal function in spontaneously hypercholesterolemic Imai rats that exhibit renal lesions similar to human focal and segmental glomerulosclerosis. The sources of proteins were from casein, pork, and fish. Primary concern was the effect of fish meat protein, because the effects of fish oil are well reported. To examine whether remnants of fish oil affect the experimental results, semi defatted fish meat and fully defatted fish meat were prepared for these experiments. METHODS: Forty-two Imai rats were placed on diets containing casein, defatted pork meat, semi-defatted fish meat, or defatted fish meat as a protein sources from 10 to 22 weeks of age. Twenty-four hour urine collections were obtained along with measurements of systolic blood pressure and drawing blood from the tail artery every 4 weeks. Finally, the kidneys were removed and prepared for histological study. RESULTS: The semi-defatted fish meat diet retarded the rise of plasma cholesterol, virtually completely prevented the development of hypertriglyceridemia, and slowed the progression of proteinuria, renal function failure, and glomerular injury as compared with the control casein diet. However, the fully defatted fish meat diet led to renal failure at the same rate as the casein diet. The defatted pork diet group exhibited a higher creatinine clearance at the end of the experiments as compared with the casein and the fully defatted fish meat diet groups. CONCLUSIONS: These data suggest that an important determinant of the protective effects of the semi-defatted fish meat diet was related to the prevention of hypercholesterolemia and hypertriglyceridemia by the remaining fish oil. Fish meat protein itself did not indicate superior beneficial effects in the regression of the renal function in Imai rats as compared with casein protein, and defatted pork showed better results than casein and fully defatted fish meat. PMID- 17347584 TI - Pravastatin inhibits carboxymethyllysine-induced monocyte chemoattractant protein 1 expression in podocytes via prevention of signalling events. AB - BACKGROUND: Up-regulation of local monocyte chemoattractant protein 1 (MCP-1) production is involved in glomerular damage through macrophage recruitment and activation in diabetic nephropathy. Advanced glycation end-products induced chemokine production in cultured mesangial cells and podocytes. Statins prevented recruitment of macrophages to the glomeruli, suggesting that statins may have the ability of anti-inflammation. In the present studies, we investigated the effects of pravastatin in the carboxymethyllysine (CML)-induced MCP-1 expression in mouse differentiated podocytes. METHODS: MCP-1 gene and protein expressions were examined using RT-PCR and ELISA. Dichlorofluorescein-sensitive intracellular reactive oxygen species (ROS) generation was measured by confocal microscopy. Activation of extracellular signal-regulated kinase (ERK), nuclear factor (NF) kappaB and Sp1 were studied using Western blotting and immunocytochemistry. RESULTS: MCP-1 was induced by CML in a time- and dose-dependent manner. CML induced MCP-1 mRNA and protein production were inhibited by 0.1 or 1 mM pravastatin. CML rapidly generated intracellular ROS in podocytes. Pravastatin did not have any ability of blocking ROS generation. Phosphorylated ERK was found in podocytes incubated with CML and was prevented by pravastatin in a dose dependent manner. Both Western blotting and immunocytochemistry results suggested that pretreatment of podocytes with pravastatin prevented the CML-induced NF kappaB and Sp1 translocation. CONCLUSION: These results suggest that pravastatin prevents CML to induce MCP-1 expression in podocytes via modulation of the intracellular ERK/NF-kappaB and Sp1 signalling pathway. PMID- 17347586 TI - Sexual oncology: sexual health issues in women with cancer. AB - Sexual problems are widespread among female cancer patients and survivors. Dysfunction may result from various oncologic therapies such as surgery, radiation therapy, chemotherapy, hormonal manipulation, and cytostatic medication. Additionally, psychologic distress that the patient or her partner experiences during diagnosis and treatment of malignancy can impair a healthy female sexual response cycle. A sexual rehabilitation program in an oncology setting is necessary to provide comprehensive care to the cancer patient and her partner. A multidisciplinary treatment approach to sexual dysfunction includes psychological and psychiatric intervention, medical intervention, cognitive behavioral therapy, and recommended lifestyle adjustments. A holistic approach to assessing and treating sexual concerns should be individually tailored to the female patient in light of her disease stage and prognosis, age, marital status, fertility concerns, and social and professional environment. PMID- 17347585 TI - Glucocorticoid receptor, nuclear factor kappaB, activator protein-1 and C-jun N terminal kinase in systemic lupus erythematosus patients. AB - OBJECTIVE: Due to the crucial role of the glucocorticoid receptor (GR), nuclear factor kappaB (NFkappaB), activator protein-1 (AP-1) and c-jun N-terminal kinase (JNK) in regulating inflammatory mediators and immune responses, we investigated their potential role in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Whole cell and nuclear extracts from peripheral blood lymphocytes, isolated from 25 SLE patients and 25 controls, were immunoblotted using GR, p65/NFkappaB, c-fos and JNK1 antibodies. The electrophoretic mobility shift assay (EMSA) assessed GR, NFkappaB and AP-1-DNA binding in nuclear aliquots. Associations with the disease state and the doses of corticosteroids administered were studied. RESULTS: (i) SLE patients had lower GR-DNA binding (p < 0.001), NFkappaB-DNA binding (p < 0.001) and whole cell c-fos (p < 0.01) but higher nuclear NFkappaB (p < 0.01). (ii) SLE patients and controls had similar AP-1-DNA binding, nuclear c-fos, GR and JNK, whole cell GR, NFkappaB and JNK. (iii) No differences were detected between active and non-active SLE or high- and low-dose corticosteroid patients. (iv) In SLE, increases in GR-DNA binding were associated with increases in NFkappaB-DNA binding (p < 0.0001), and increases in nuclear JNK were associated with increases in AP-1-DNA binding (p < 0.01). (v) In controls, increases in GR DNA binding were associated with increases in AP-1-DNA binding (p < 0.001). CONCLUSION: We suggest disturbed GR, NFkappaB, AP-1 and JNK signaling in SLE, characterized by a reduced GR- and NFkappaB-DNA binding, a significant association between GR-mediated and NFkappaB-driven pathways, and a significant correlation between nuclear JNK- and AP-1-driven pathways. These disturbances may contribute to abnormal cytokine production and the etiopathogenesis of SLE. PMID- 17347587 TI - Microarrays of 41 human tumor cell lines for the characterization of new molecular targets: expression patterns of cathepsin B and the transferrin receptor. AB - In recent years the use of the microarray technology has allowed the identification of numerous cancer-related genes and proteins. Today anticancer drug discovery is mainly target driven, which requires the characterization of molecular targets in existing cell lines or xenograft models. However, this analysis is time consuming and labor intensive. In order to ease this bottleneck, we have established tissue microarrays of 41 human tumor cell lines on glass slides. The purpose of our study was to (a) establish a simple and efficient method for cell line microarray construction, (b) apply the resulting array to the profiling of cathepsin B and transferrin receptor by immunohistochemistry and (c) verify the results in separate Western blot analyses. Ten to twenty million (1-2 x 10(7)) cells were harvested without trypsinization and fixed with Bouin's solution containing 8% formalin. Cell pellets 2-5 mm in diameter were embedded in paraffin. Microarrays were assembled using a tissue arrayer. Pellet biopsies 0.6 cm in diameter were taken and arrayed in duplicate in a new recipient paraffin block. About 60 slides can be obtained from one block. Citrate buffer was used for antigen retrieval. Expression of cathepsin B was granular and located in the cytoplasm. High cathepsin B levels were detected in 2 melanomas (MEXF 514L and MEXF 276L) and in the renal cell line RXF 486L. Twenty-five cell lines showed only minimal positivity. Nine cell lines of leukemia and lymphoma, breast, ovarian, prostate and renal cancer origin were positive for the transferrin receptor, while 32 cell lines were negative. Western blotting confirmed the results obtained by immunohistochemistry. Using these cell line microarrays, cell lines overexpressing a target of interest can be selected for in vitro evaluation of specific inhibitors. PMID- 17347588 TI - Mild inflammation accelerates colon carcinogenesis in Mlh1-deficient mice. AB - OBJECTIVE: Inflammatory bowel disease, which frequently accompanies silencing of Mlh1, plays a key role in the pathogenesis of colorectal cancer. The interaction between inflammation and mismatch repair deficiency, however, remains unclear. The aim of this study was to determine the effect of inflammation on colorectal carcinogenesis in Mlh1-deficient mice. METHOD: Inflammatory colitis was induced by treatment with 1% dextran sodium sulfate (DSS) in drinking water for 1 week in Mlh1 knockout (Mlh1(-/-)), Mlh1 heterozygous (Mlh1(+/-)) and wild-type (Mlh1(+/+)) mice at 10 weeks of age. The development of colon tumors was followed for a subsequent 15 weeks and the tumors were analyzed immunohistochemically for the expression and localization of iNOS, beta-catenin and p53. RESULTS: Male and female Mlh1(-/-) mice with DSS showed a 63 and 44% incidence of tumors, respectively, whereas no tumors were observed in Mlh1(+/-) and Mlh1(+/+) mice. The mice without DSS treatment did not develop any tumors regardless of the genotype. While aberrant expression of beta-catenin was not detected in colonic neoplasms, p53 and iNOS expression was increased in 100 and 77%, respectively. These immunohistochemical changes were consistent with those of human colon cancers associated with ulcerative colitis. CONCLUSION: Our results indicate that Mlh1 deficiency strongly accelerates colon carcinogenesis when combined with inflammation. Thus the cells with Mlh1 deficiency, either inherently or colitis associated, may be at an increased risk of cancer under inflammatory conditions. PMID- 17347589 TI - Difference in the role of loss of heterozygosity at 10p15 (KLF6 locus) in colorectal carcinogenesis between sporadic and familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer patients. AB - OBJECTIVES: To clarify the role of the KLF6 (Kruppel-like factor 6) locus in multistep colorectal carcinogenesis, we analyzed loss of heterozygosity (LOH) at 10p15 (KLF6 locus) and mutations of the KLF6gene in 298 colorectal tumors at various pathological stages of sporadic and familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) patients. METHODS: 10p15 LOH was analyzed using KLF6M1 and KLF6M2, and KLF6 gene mutation was analyzed using PCR-SSCP and sequencing. RESULTS: It was found that the frequencies of LOH (sum of M1 and M2) were 4% in adenomas, 0% in intramucosal carcinomas, 35% in invasive carcinomas, and 33% in liver metastases in sporadic cases. Invasive carcinomas from FAP patients showed only 6% LOH, and invasive carcinomas from HNPCC patients exhibited 0% LOH. Mutation analysis of the KLF6 gene in 298 colorectal tumors detected no somatic mutations. CONCLUSIONS: The present data suggest that LOH of the KLF6 locus at chromosome 10p15 contributes to the invasion step from an intramucosal carcinoma to an invasive carcinoma specifically in sporadic colorectal carcinogenesis, but is rarely involved in the carcinogenesis of FAP and HNPCC cases. Moreover, the absence of somatic mutations suggests the uncertainty of the KLF6 gene as a classical tumor suppressor gene at the lost 10p15 region in colorectal carcinogenesis. PMID- 17347590 TI - Presentations of phase 2 clinical trial abstracts at a national oncology meeting: potential implications for subsequent publication in the peer-reviewed literature. PMID- 17347591 TI - [Symptoms and natural course of food allergies]. PMID- 17347592 TI - [Diagnostic method for food allergies]. PMID- 17347593 TI - [Diagnosis and treatment of chronic cough -an overview]. PMID- 17347594 TI - [Allergy and respiratory diseases in Asia Pacific and Japan]. PMID- 17347595 TI - [Influence of genes and environment on allergic disorders]. PMID- 17347596 TI - [Allergen activity of xerophilic fungus, Aspergillus restrictus]. AB - BACKGROUND AND PURPOSE: The typical xerophilic fungi, Aspergillus restrictus, have been very frequently detected in house dust by low water activity medium. Since the composition of fungal allergens are affected culture and extract condition, we considered the influence in A. restrictus in order to develop new allergen of xerophilic fungi. METHOD: The 4 different extract of A. restrictus were obtained from various fermentation and extraction methods. These extracts were studied for specific IgE in sera of patients with asthma. The cross reactivity between A. restrictus and A. fumigatus were analyzed by enzyme-linked immunosorbent assay (ELISA) inhibition. Then, component analysis of A. restrictus allergens was examined by SDS-PAGE and Western Blotting. RESULT: In ELISA, IgE antibodies against four extracts of A. restrictus were found in sera of 20-48%. In ELISA inhibition using sera obtained from 11 asthma patients, A. fumigatus antigen solution inhibited the reaction of A. restrictus with 5 asthma patients. CONCLUSION: These results indicated that A. restrictus may be important as a causative agent in adult asthma patients. However, it was suggested that some preparation methods of an extract influence activity. Furthermore, cross reactivity was found between A. restrictus and A. fumigatus. PMID- 17347597 TI - [Correlation between the SF-8 health status questionnaire and JRQLQ in patients with Japanese cedar pollinosis]. AB - BACKGROUND: It is reported that the health-related quality of life (HRQL) is an important outcome in the Japanese Cedar Pollinosis (JCP) treatment. In Japan, the disease-specific Japan Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ) and the generic SF-36 Health Survey (SF-36) has been used. The aim of this study is to investigate more profitable QOL by using both the disease-specific questionnaire and the non-disease-specific questionnaire together. METHODS: 411 patients with JCP who visited 10 ENT clinics in Osaka from March 14 to March 26 (peak pollen season) in 2005 were questioned, and 240 patients were engaged in this study as subjects. In this study, the QOL scores were evaluated using the JRQLQ and SF-8 Health Survey (Japanese Version), a new, even shorter generic health survey. RESULTS: Using factor analysis and the correlation matrix, we showed that the disease-specific and the general health instrument covered a different half the total measurable HRQL. There was some correlation between the SF-8 items with the JRQLQ domains. There was little correlation between the SF-8 items and symptom scores, while, there was high correlation between the JRQLQ and symptom scores. The "Usual daily activities" domain in the JRQLQ correlated with any rhinoconjunctivitis symptoms. CONCLUSION: Both JRQLQ and SF-8 can be used to assess the quality of life of patients with JCP. Each instrument measures the aspects of the HRQL that hardly overlaps. For an assessment of the HRQL in JCP that is complete and responsive both instruments should be employed together. PMID- 17347598 TI - [Haematological pulmonary disease, an avenue to explore]. PMID- 17347599 TI - [Malformations of the anterior chest wall]. AB - INTRODUCTION: Pectus excavatum or funnel chest is the most common anterior chest wall deformity seen in children and adults. The sternal depression appears to be caused by overgrowth of the costal cartilages, also the cause of the less common deformities: pectus carinatum (pigeon breast) and pectus arcuatum. BACKGROUND: Usually the overgrowth involves the third to seventh costal cartilages but it can be more or less extensive. The cardiopulmonary functional consequences are insignificant in the protrusional deformities and inconsistent in pectus excavatum and the indications for surgery are mainly cosmetic. VIEWPOINT AND CONCLUSIONS: The procedural modalities are guided by morphological study of the CT scan. We describe a surgical technique that comprise subperichondrial excision of all deformed costal cartilages followed by transverse sternotomy to correct the sternal deformity, anteriorly in the case of pectus excavatum and posteriorly for pectus carinatum and arcuatum. As the perichondrial sheaths are totally preserved they are sutured in continuous layers to give a shortening effect. In the case of pectus excavatum the sternum is then secured anteriorly for about 6 months by a retrosternal metallic strut in an overcorrected position. The partially resected seventh cartilages are then sutured to the xiphoid. Other surgical techniques are described, including modified Ravitch's procedure, modelling osteochondroplasty, prosthetic reconstruction and Nuss's procedure. Results of the more important series are reported and discussed. PMID- 17347600 TI - [What are the post-rehabilitation options for patients with COPD?]. AB - INTRODUCTION: The efficacy of pulmonary rehabilitation in the short term for patients with Chronic Obstructive Pulmonary Disease (COPD) is now clearly established. However, several studies have shown that these benefits last only for between 6 months to one year. On the basis of the current literature, the authors believe that a follow-up of rehabilitation "post-rehabilitation" is necessary not only to maintain benefits but also to reinforce them. STATE OF THE ART: We review studies that have focused specifically on post-rehabilitation and found a heterogeneity of tested solutions. As with conventional pulmonary rehabilitation, a multidisciplinary approach including physical activity, health education and psychosocial supports seem to be the key to successfully maintain rehabilitation's gains. PERSPECTIVES: Further randomised and controlled research will be needed to confirm the medical and economic effectiveness of this combination of intervention in patients with different severities of COPD. CONCLUSION: Individualised, objective and coordinated follow-up activities allow COPD patients to cope with the chronicity of their disease and the unpredictability of symptoms in the context of daily life. PMID- 17347601 TI - [Passive smoking in France: science, law and judge's point of view]. AB - INTRODUCTION: Passive smoking occurs as a consequence of exposure to indoor atmospheric pollution by tobacco smoke. Its effects on health are now scientifically established. BACKGROUND: The 1976 "Veil"'s law was the first law related to the fight against passive smoking. It introduced a first step towards respecting the rights of non-smokers in premises and public transport. In 1991, the law "Evin" augmented it. Health messages appeared on the cigarette packets and the law prohibited exposure to smoke in public places, except in the sites reserved for smokers. The right of non-smokers not to be exposed to tobacco smoke was recognized. In practice, 15 years later, the law is still not enforced, so that the health of non-smokers is still not effectively protected. PERSPECTIVES AND CONCLUSIONS: Tobacco smoke is the second most common carcinogen to which employees are exposed. Workers in bars, restaurants and night-clubs are particularly vulnerable and display significant increases in biological markers of exposure. On June 29th 2005, the "Cour de Cassation" recognized that an employee had the right to sue their employer for breach of contract because they did not effectively implement a general and absolute prohibition on smoking in their offices, thus recognizing a legal obligation on employers to prevent exposure to tobacco smoke. This decision opens a new frontline in the fight against tobacco, while waiting for new legislative or governmental action to protect non-smokers at work effectively. PMID- 17347602 TI - [Management of the pulmonary complications of haematological malignancy]. AB - The high frequency of pulmonary complications of haematological malignancy and the increasing number of patients treated for these disorders make it important that the respiratory physician has a structured diagnostic approach according to: 1 the immune deficiency due to the malignancy and/or the treatment administered; 2 the factors that can modify the risk of infection (anti infection prophylaxis and/or pre-emptive treatment); 3 co-morbidities; 4 extra-pulmonary manifestations. Two main situations can be identified: The patient is aplasic: Initially the pneumonias are predominantly of bacterial origin but may be fungal if the neutropenia is prolonged. The respiratory physician is faced with two problems: 1 the diagnosis of pneumonia; this may be helped by CT scanning; 2 The choice of antibiotics; this will depend on previous investigations. The patient is not aplasic: The lung disease may have many causes, mainly infectious but also drug related, tumoral, haemorrhagic or embolic. The main problem is the correct choice of investigations to establish an aetiological diagnosis. The collection of data according to a pre-established protocol based on simple factors (study of the notes and clinical examination) is one of the key elements for improving the prognosis of these patients whose management should be multidisciplinary following a pre-defined plan. PMID- 17347603 TI - [Imaging of pulmonary arterial hypertension]. AB - INTRODUCTION: The investigation of pulmonary arterial hypertension (PAH) requires a rigorous aetiological assessment in which imaging modalities play an important role. BACKGROUND: The chest x-ray may show non-specific signs such as cardiomegaly and dilatation of the pulmonary arteries, and also allows examination of the lung parenchyma. Echocardiography is the essential screening tool and allows evaluation of left ventricular function. Pulmonary ventilation/perfusion scanning is essential to confirm post embolic PAH. Spiral CT has become an essential examination. It allows detailed study of the lung parenchyma, the pulmonary vessels and the cardiac chambers, and also helps determine the aetiology and complete the pre-treatment assessment. Magnetic resonance imaging allows calculation of several haemodynamic parameters and morphological study of the cardiac chambers and pulmonary vessels but requires further evaluation. VIEWPOINT: The improvement in the quality of vascular images and the development of complementary MRI techniques may lead to increase of this modality in the study of PAH. CONCLUSION: Imaging plays a fundamental role in the management of patients suffering from PAH. PMID- 17347604 TI - [The contribution of cognitive-behavioural therapies to smoking cessation]. AB - INTRODUCTION: Behavioural therapies have been developed on the basis of Pavlov's and Skinner's learning theories. They have recently benefited from advances in the understanding of information handling and the organisation of perceptions of experience. It is for these two reasons that these treatments are called cognitive behaviour therapies (CBT). They have now achieved an important role in the treatment of addictions including tobacco smoking. Currently CBT's are seen as promising because they rely on cognitive restructuring combined with learning of new behaviour while following a process appropriate to the changing dynamic of the smoker. BACKGROUND: They have recently been recognised as of grade A effectiveness by the French Institute of Medical Research and may be recommended to all smokers whose primary intention is to stop. The establishment of a collaborative rapport and a therapeutic attitude are essential. They may be used during the three stages of cessation: preparation, stopping, and the prevention of relapse. A personalised functional analysis provides the patient with a management program using behavioural and, above all, cognitive techniques. The ideal is to combine a pharmacological and an optimised cognitive-behavioural approach. VIEWPOINT: The management of smoking patients has advanced with the understanding of a very complex problem, often associated with anxiety-depressive co-morbidities and other addictions. Tobacco specialists, psychiatrists, cognitive-behavioural therapists and addiction therapists must work together in the future, particularly in respect of research protocols. CONCLUSIONS: Cognitive behavioural therapy is a useful technique in the personalisation and optimisation of management of the patient, particularly in the prevention of relapse. However, the evaluation of CBT is difficult methodologically and there are few studies evaluating CBT alone. On the other hand, CBT is effective, particularly where there are anxiety or depressive co-morbidities or other addictions that are found more and more frequently during consultations for tobacco smoking. PMID- 17347605 TI - [Evaluating care in community acquired pneumonia]. AB - INTRODUCTION: Evaluations of care strategies for patients with community acquired pneumonia (CAP) tend to focus more on their necessity (variation in practice...) than on efficacy (adherence, impact of markers of disease severity or medico economic factors...). STATE OF THE ART: A number of studies are reported in the literature based on a simple evaluation of practice at a given moment on time or else on the impact of guidelines. These evaluations relate either to outcome criteria (mortality, and duration of stay especially) or the economic impact of CAP (rate of hospitalization, duration of stay, costs of the treatments or hospitalizations...), or on process of care (evaluation of initial severity, delay in administration of antibiotics, appropriateness of antibiotic therapy, evaluation of oxygenation and taking of specimens prior to treatment). PERSPECTIVES AND CONCLUSIONS: Taken together these studies demonstrate the need to improve and standardise care. Where studies have not found a benefit from guidelines this can often be attributed to problems with assessment or study design and there are many studies showing the benefit of guideline based management and the introduction of standardised care pathways. PMID- 17347607 TI - [Occupational rhinitis]. AB - INTRODUCTION: Rhinitis is one of the most common occupational diseases. It is often neglected by those affected because it causes little disability. It is poorly understood by doctors who have insufficient experience of occupational diseases and their causes. However it is often the first manifestation of a respiratory disorder that may cause physical complications and socio-economic disability. BACKGROUND: Numerous diverse agents are potential causes of rhinitis. The diagnosis of occupational rhinitis should be considered when sneezing, rhinorrhoea or nasal obstruction are associated with work. The causal agent can be identified by ta-king a careful history. When the mechanism of the disease is immunologic the suspected antigen can be confirmed by skin testing, specific IgE or nasal provocation. The respiratory disorder of which rhinitis is the first manifestation may progress to asthma if the exposure continues. The prevention of occupational rhinitis depends on the reduction of exposure to allergens and/or irritants. When it has developed removal of the causative agent is essential to prevent progression to asthma. PMID- 17347606 TI - [Assessment of quality of care in asthma]. AB - INTRODUCTION: Asthma is a chronic airways disease characterised by variable and reversible airflow obstruction. It is highly prevalent and incurs high costs, inducing a particular consideration from health authorities (an Asthma Plan has already been published and is part of the new public heath law). BACKGROUND: In order to assess the appropriateness of care delivered, it is important to take into account several parameters: mortality, acute asthma management, hospitalisations, costs, and other parameters such as DALY. It is also important to consider occupational asthma. All the terms (variable, reversible, chronic) that allow identification of asthma explain the difficulties in producing an efficient management strategy and good quality care. PERSPECTIVES: Public heath policy has to address the availability of these different management strategies. Medical doctors and all other health professionals need to adapt themselves to the needs of patients and their disease. Finally, patients have to be involved in the management of their own disease. Their active involvement will make it possible to significantly improve the quality of care. CONCLUSION: During the past 20 years, significant improvements have been achieved in basic and clinical science but more data are needed to improve the practical management of asthmatic patients. PMID- 17347608 TI - [Introduction for short texts from "La conference d'experts de la Societe de Pneumologie de Langue Francaise (SPLF) sur Asthme et Allergie"]. PMID- 17347609 TI - [SPLF Guidelines on Asthma and Allergy]. PMID- 17347610 TI - [Respiratory diseases, allergies and closed environment]. PMID- 17347611 TI - [Home pollutants: where does France stand?]. PMID- 17347612 TI - [Elimination of allergens: where do we stand?]. PMID- 17347613 TI - [Elimination of allergens and chemical pollutants from the habitat, which practical proportions, which materials to use?]. PMID- 17347614 TI - [Moulds in indoor environments: sampling and measurement techniques]. PMID- 17347615 TI - [Moulds in indoor environments and respiratory diseases]. PMID- 17347616 TI - [Lung cancer and indoor environment]. PMID- 17347617 TI - [Legionellosis and mycobacteriosis associated with the habitat: measurement techniques, pathogenic thresholds and role of the lung specialist]. PMID- 17347618 TI - [Recommendations for the clinical management and treatment of chronic constipation in adults]. PMID- 17347619 TI - [Recent advances for the identification and screening of Lynch syndrome]. PMID- 17347620 TI - Cytokines pattern after surgical radiofrequency ablation of liver colorectal metastases. AB - AIMS: The aim of this study was to evaluate the serum pattern of cytokines evolution after surgical radiofrequency ablation (SRFA) of colorectal metastases. METHODS: Metastases of ten non consecutive patients were destroyed by radiofrequency ablation without concomitant resection after a complete surgical procedure including a laparotomy, a peritoneal examination, liver mobilisation and liver ultrasound. Serum levels of IL-6, TNFalpha, HGF, VEGF, bFGF, TGFbeta1 and CRP were assessed by ELISA assays at different time points. RESULTS: TNFalpha and bFGF remained undetectable. IL-6 peaked at 3 hours and remained elevated during the entire study period. HGF increased by three-fold by Day 1 then decreased until Day 7 where it was still twice its baseline level. VEGF level increased from Day 5 onward. TGFbeta1 did not show significant variations. CRP was increased throughout the study. CONCLUSIONS: In contrast with cryotherapy, SRFA does not lead to high serum TNFalpha suggesting a better tolerance. Nevertheless high IL-6, HGF and VEGF serum levels are characteristic of a general inflammatory stress which should be taken into account. PMID- 17347621 TI - [Intrabiliary metastasis in colorectal cancer]. AB - Endobiliary metastasis of colorectal cancers are rare. We report a 36 years-old patient, operated on 5 years ago for a left colon cancer with a left colectomy. He consulted for pain in the upper right quadrant without fever nor jaundice. Ultra-sound, CTscan, RMI and PET led to the diagnosis of endobiliary metastasis and the patient underwent a right hepatectomy. A review of the literature of the endobiliary metastasis follows this case-report. These tumours can mimic intrahepatic cholangiocarcinoma in clinical presentation, imaging or even histological examinations. The main goal of the imaging explorations is to establish the resecability of such tumours. Patients with endobiliary metastasis seem to have better survival than patients with intrahepatic metastasis. PMID- 17347622 TI - [Colobiliary fistula with a liver abscess complicating adenocarcinoma of the ascending colon]. PMID- 17347623 TI - Chemotherapy as initial treatment of locally advanced unresectable pancreatic cancer: a valid option? AB - INTRODUCTION: Radio-chemotherapy is the standard treatment for locally advanced unresectable pancreatic cancer (LAPC). Chemotherapy has been shown to be effective in the treatment of metastatic disease and we therefore evaluated its use as a first-line treatment for LAPC. PATIENTS AND METHODS: We carried out a retrospective analysis of all consecutive patients treated for LAPC (N=33) between July 1997 and April 2005, analysing the results of first-line chemotherapy (CT group) and radio-chemotherapy (RCT group) in this setting. RESULTS: The first-line treatment was RCT in six patients (18.3%) and CT in 26 patients (78.8%). Secondary treatment was administered to nine patients of CT group with well-controlled disease: "closure" radio-chemotherapy for seven patients (26.9%) and secondary resection for three (12%). After a median follow up of 27 months, 23 patients died (69.7%). Overall survival was 13.8 months [95% CI: 10.1-19.4] for the whole population, 9.5 months [95% CI: 4.6-] for the RCT and 18.0 months [95% CI: 12.4-25.5] for the CT. Overall survival for the CT patients undergoing secondary surgery or "consolidation" radio-chemotherapy was 28.8 months [95% CI: 13.8-]. CONCLUSION: First-line chemotherapy is a valid option for LAPC treatment, making it possible to identify the patients who may benefit from secondary resection or radio-chemotherapy. PMID- 17347624 TI - [Initial pretherapeutic assessment of anal epidermoid carcinoma]. AB - Anal epidermoid carcinoma is a rare malignant tumor, comprising less than 5% of all carcinomas of the colon, rectum, and anus. The primary therapy now includes radiotherapy, often in combination with chemotherapy. Radical surgery is now rarely indicated. Therapeutic indications are based on locoregional staging, the presence of visceral metastases and an evaluation of the medical history. Anorectal endosonography is helpful in evaluating locoregional extension. In addition, magnetic resonance imaging, positron emission tomography scanning and inguinal sentinel lymph node procedure should play a role in a more selective approach in patients with anal carcinoma. PMID- 17347625 TI - An uncommon perianal nodule: hidradenoma papilliferum. AB - Hidradenoma papilliferum is a rare, benign, cystic, papillary apocrine gland tumor that occurs almost exclusively in women in the skin of the anogenital region. We present the case of a 66 year old woman who presented with a progressively enlarging perianal nodule. We provide a review of the literature emphasizing the clinico-pathological characteristics and differential diagnosis. Local excision is necessary for identification and cure. No recurrence was observed after one year follow-up. PMID- 17347626 TI - Management and predictors of early mortality in elderly patients with iron deficiency anemia: a prospective study of 111 patients. AB - OBJECTIVES: Iron deficiency anemia (IDA) is common in the elderly. It usually results from gastrointestinal (GI) bleeding and requires endoscopic exploration of the gastrointestinal tract. The aim of this prospective study in elderly patients was to evaluate the feasibility of endoscopy, the therapeutic impact, and identify predictors of early mortality. METHODS: From June 2003 to May 2005, all patients over 75 years, hospitalized for anemia were screened for iron deficiency. Clinical (including serious comorbidities), biological, endoscopic and therapeutic data were collected. One month after treatment, a follow-up was carried out to assess the tolerance of such investigation and treatment. RESULTS: One hundred and eleven patients (69 women, 82.3 +/- 6.4 years) had IDA, 102 (92%) underwent an upper endoscopy and 91 (82%) a colonoscopy. Nine (8%) patients were not investigated because of poor clinical condition (N=4) or dementia (N=5). Of the 75 (68%) patients with an identified source of bleeding, 12 (11%) had a synchronous lesion, 43 (39%) a colorectal source including 31 (72%) colorectal cancer, and 44 (40%) an upper GI source. Sixty-nine (92%) of the 75 patients received at least one of the following treatments: medical (N=27), endoscopic (N=20), and surgical (N=31). Surgery was curative in 28/31 (90%) cases of which 25/27 were colorectal cancers. One month after treatment, overall mortality was 11/111 (10%) and 4/31 (13%) after surgery. Predictors of early mortality (Odd ratio, 95% Confidence Interval) were: a malign cause (42; 3-588), no specific treatment (34; 3-423), at least 2 co-morbidities (20; 1-400). CONCLUSION: In an unselected hospitalized population of elderly patients with IDA, endoscopy was generally feasible, allowing identification of a source of bleeding, especially colorectal cancer. A specific treatment was usually possible and proved curative without increase in early mortality. PMID- 17347627 TI - [Organ donors after cardiac death: what role do they play in liver transplantation?]. PMID- 17347629 TI - [Compensation of victims of nosocomial or post-transfusion hepatitis C virus infection]. AB - The purpose of this review is to inform physicians about the procedures for compensation of victims of nosocomial or post-transfusion hepatitis C virus infection. The different procedures are described in reference to the legislation and regulations. According to the law dated March 4, 2002 if Hepatitis C is contracted during care, in a private or public hospital, the hospital (and not the physician) is responsible for the damages resulting from the nosocomial infection, except if evidence of another cause is provided. For post-transfusion hepatitis C, the patient must show that a transfusion took place prior to the diagnosis of hepatitis C. The patient must also prove that there were no other sources of infection. The French Institute of Blood can sometimes not be held responsible by proving that none of the donors of the transfused blood were infected with the hepatitis C virus. This is a no fault system. Different examples of litigation show the important role of physicians, who must be aware of the main points of the procedures to better understand what is entailed by the medical certificates which the victim may request and also to provide him with any other steps to be taken to obtain compensation. PMID- 17347628 TI - Satisfaction of patients treated for chronic hepatitis C with the peginterferon alfa-2b pen device: the VISA observational study. AB - OBJECTIVES: This observational study aimed at evaluating the satisfaction of patients with chronic hepatitis C using the peginterferon (peg-IFN) alfa-2b pen device. METHODS: Consecutive patients were included when prescribed the pen device. Self-administered questionnaires relating to the progress brought by the pen, convenience/comfort, and the mode and security of injection were completed after the first injection and at 12 weeks. RESULTS: Six hundred and forty eight patients aged 45.7 +/- 12.1 years completed the 1st questionnaire; 70% were naive for any hepatitis C treatment. Five hundred and twenty five (81%) patients completed the 2nd questionnaire. Adherence to the pen device was >or=80% in more than 80% of the patients. Most (85%) patients declared that the pen brought important progress compared to traditional syringes. Satisfaction was high after the 1st injection and further increased 12 weeks later, with ease of use scoring 7.7 then 8.0 (P=0.007, 10-point scale), and rapidity of use scoring 8.0 then 8.2 (P=0.008); less painful injection scoring 7.9 at both time points. The proportion of self-injectors (no intervention of a health professional) increased from 32% to 58% (P<0.0001). Reasons for self-injecting were: easier injection (58%), no product/syringe handling (50%/41%), and assurance of exact dosing (45%). CONCLUSION: Patients were satisfied with the peg-IFN alfa-2b pen device. The proportion of self-injectors doubled over 12 weeks. Good treatment adherence, which is mandatory for therapeutic success, is expected from use if this device. PMID- 17347630 TI - [Vitamin B12 deficiency revealing asymptomatic Crohn's disease]. PMID- 17347631 TI - [Acute idiopathic polyneuritis: a potentially fatal neuropathy that is difficult to diagnose in patients receiving oxaliplatin]. PMID- 17347632 TI - Endoscopic management of a large choledochocele associated with choledocholithiasis. AB - Choledochocele or type III choledochal cyst is a very rare lesion, defined as a cystic dilatation of the distal common bile duct protruding into the duodenal lumen. Abdominal pain, biliary disorders, and acute pancreatitis are frequently observed but malignant degeneration is rare. A 70-year-old man had a history of epigastralgia associated with abnormal liver function tests suggesting gallstones. During laparoscopic cholecystectomy, intraoperative cholangiography showed a 40-mm-diameter choledochocele associated with choledocholithiasis. A transcystic drain was placed after cholecystectomy had been completed. Endoscopic retrograde cholangiopancreatography confirmed the diagnosis and a 45-mm-long endoscopic sphincterotomy successfully treated both lesions as confirmed by a transcystic cholangiogram showing a thin-walled common bile duct with no residual stones. This case illustrates that the diagnosis of choledochocele remains difficult in clinical practice and confirms that endoscopic retrograde cholangiopancreatography is the best available diagnostic tool. Coexistent choledocholithiasis is observed in about 20% of choledochocele. Endoscopic sphincterotomy is feasible and effectively treats both lesions even in larger choledochoceles. PMID- 17347633 TI - [Hepatic vein thrombosis after transjugular liver biopsy]. PMID- 17347634 TI - [Hepatotoxicity of carbamazepine: a case of "DRESS syndrome"]. PMID- 17347636 TI - [Incidental discovery of cystic lesions of the pancreas]. PMID- 17347637 TI - [Adenocarcinomas of the pancreas: how best to evaluate resectability?]. PMID- 17347638 TI - [Treatment strategy of acute pancreatitis: parenteral nutrition and preventive antibiotic therapy]. PMID- 17347639 TI - [How to evaluate non-alcoholic non-biliary acute pancreatitis]. PMID- 17347640 TI - [Neo-adjuvant and adjuvant treatments of pancreatic cancer]. PMID- 17347641 TI - [Case report: pancreatic endocrine tumor]. PMID- 17347642 TI - Racial/ethnic disparities in diagnoses of HIV/AIDS--33 states, 2001-2005. AB - During 2001-2004, blacks accounted for 51% of newly diagnosed human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) infections in the United States. This report updates HIV/AIDS diagnoses during 2001-2005 among black adults and adolescents and other racial/ethnic populations reported to CDC through June 2006 by 33 states that had used confidential, name-based reporting of HIV and AIDS cases since at least 2001. Of the estimated 184,991 adult and adolescent HIV infections diagnosed during 2001-2005, more (51%) occurred among blacks than among all other racial/ethnic populations combined. Most (62%) new HIV/AIDS diagnoses were among persons aged 25-44 years; in this age group, blacks accounted for 48% of new HIV/AIDS diagnoses. New interventions and mobilization of the broader community are needed to reduce the disproportionate impact of HIV/AIDS on blacks in the United States. PMID- 17347643 TI - Influenza vaccination coverage among children with asthma--United States, 2004-05 influenza season. AB - In 2005, approximately 8.9% (6.5 million) of U.S. children aged <18 years were reported to have current asthma. Children with asthma are at high risk for complications from influenza, and influenza vaccination has been determined to safely and effectively reduce rates of influenza in these children. Since its establishment in 1964, the Advisory Committee on Immunization Practices (ACIP) has recommended that all children with asthma aged > or =6 months receive vaccination with inactivated influenza vaccine during each influenza season; however, national influenza vaccination coverage rates specifically for children with asthma have not been determined. Previous studies have assessed influenza vaccination rates in children with asthma at the local level using health maintenance organization and clinician group-practice information, with estimates ranging from 10% to 43% for various influenza seasons. Another study used Behavioral Risk Factor Surveillance System (BRFSS) data to estimate influenza vaccination coverage in children aged 2-17 years with one or more conditions putting them at high risk for complications from influenza (including asthma, although asthma was not assessed separately); in that study, the national rate was estimated at 34.8% for the 2004-05 influenza season (based on a sample size of 685, which included all states and the District of Columbia [DC]). To estimate national influenza vaccination coverage rates among children aged 2-17 years with current asthma, CDC analyzed data from the 2005 National Health Interview Survey (NHIS). This report describes the results of that analysis and provides the first national estimates of influenza vaccination coverage among children with asthma. The findings indicated that although children with current asthma were more likely to receive influenza vaccination than children without current asthma, the vaccination coverage rate among children with asthma was low, at 29.0% (95% confidence interval [CI] = 24.5-33.9). These findings underscore the need to increase influenza vaccination coverage in children with asthma aged 2-17 years by identifying and overcoming barriers to vaccination. PMID- 17347644 TI - Invasive methicillin-resistant Staphylococcus aureus infections among dialysis patients--United States, 2005. AB - Staphylococcus aureus is a leading cause of bloodstream and other invasive infections in the United States. S. aureus has become increasingly resistant to first-line antimicrobial agents in health-care settings. Dialysis patients are especially vulnerable to infections, frequently those caused by antimicrobial resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). To assess the incidence of invasive MRSA infection among dialysis patients in the United States during 2005, surveillance data were analyzed from the Active Bacterial Core surveillance (ABCs) system. This report summarizes the results of that analysis, which estimated that, in 2005, the incidence of invasive MRSA infection among dialysis patients was 45.2 cases per 1,000 population. Persons receiving dialysis are at high risk for infection with invasive MRSA compared with the general population, in which rates of invasive MRSA have ranged from 0.2 to 0.4 infections per 1,000 population. The findings in this report underscore the need for continued surveillance and infection-control strategies aimed at reducing infection rates and preventing additional antimicrobial resistance among persons receiving dialysis. PMID- 17347645 TI - Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. AB - Functional crosstalk between cell-surface and intracellular ion channels plays important roles in excitable cells and is structurally supported by junctophilins (JPs) in muscle cells. Here, we report a novel form of channel crosstalk in cerebellar Purkinje cells (PCs). The generation of slow afterhyperpolarization (sAHP) following complex spikes in PCs required ryanodine receptor (RyR)-mediated Ca(2+)-induced Ca(2+) release and the subsequent opening of small-conductance Ca(2+)-activated K(+) (SK) channels in somatodendritic regions. Despite the normal expression levels of these channels, sAHP was abolished in PCs from mutant mice lacking neural JP subtypes (JP-DKO), and this defect was restored by exogenously expressing JPs or enhancing SK channel activation. The stimulation paradigm for inducing long-term depression (LTD) at parallel fiber-PC synapses adversely established long-term potentiation in the JP-DKO cerebellum, primarily due to the sAHP deficiency. Furthermore, JP-DKO mice exhibited impairments of motor coordination and learning, although normal cerebellar histology was retained. Therefore, JPs support the Ca(2+)-mediated communication between voltage-gated Ca(2+) channels, RyRs and SK channels, which modulates the excitability of PCs and is fundamental to cerebellar LTD and motor functions. PMID- 17347646 TI - Cleavage of a bacterial autotransporter by an evolutionarily convergent autocatalytic mechanism. AB - Bacterial autotransporters are comprised of an N-terminal 'passenger domain' and a C-terminal beta barrel ('beta domain') that facilitates transport of the passenger domain across the outer membrane. Following translocation, the passenger domains of some autotransporters are cleaved by an unknown mechanism. Here we show that the passenger domain of the Escherichia coli O157:H7 autotransporter EspP is released in a novel autoproteolytic reaction. After purification, the uncleaved EspP precursor underwent proteolytic processing in vitro. An analysis of protein topology together with mutational studies strongly suggested that the reaction occurs inside the beta barrel and revealed that two conserved residues, an aspartate within the beta domain (Asp(1120)) and an asparagine (Asn(1023)) at the P1 position of the cleavage junction, are essential for passenger domain cleavage. Interestingly, these residues were also essential for the proteolytic processing of two distantly related autotransporters. The data strongly suggest that Asp(1120) and Asn(1023) form an unusual catalytic dyad that mediates self-cleavage through the cyclization of the asparagine. Remarkably, a very similar mechanism has been proposed for the maturation of eukaryotic viral capsids. PMID- 17347647 TI - Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi membranes. AB - ARHGAP21 is a Rho family GTPase-activating protein (RhoGAP) that controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. ARHGAP21 is recruited to the Golgi by binding to another small GTPase, ARF1. Here, we present the crystal structure of the activated GTP-bound form of ARF1 in a complex with the Arf-binding domain (ArfBD) of ARHGAP21 at 2.1 A resolution. We show that ArfBD comprises a PH domain adjoining a C-terminal alpha helix, and that ARF1 interacts with both of these structural motifs through its switch regions and triggers structural rearrangement of the PH domain. We used site-directed mutagenesis to confirm that both the PH domain and the helical motif are essential for the binding of ArfBD to ARF1 and for its recruitment to the Golgi. Our data demonstrate that two well known small GTPase-binding motifs, the PH domain and the alpha helical motif, can combine to create a novel mode of binding to Arfs. PMID- 17347648 TI - Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. AB - In mammals, maintenance of energy and nutrient homeostasis during food deprivation is accomplished through an increase in mitochondrial fatty acid oxidation in peripheral tissues. An important component that drives this cellular oxidative process is the transcriptional coactivator PGC-1alpha. Here, we show that fasting induced PGC-1alpha deacetylation in skeletal muscle and that SIRT1 deacetylation of PGC-1alpha is required for activation of mitochondrial fatty acid oxidation genes. Moreover, expression of the acetyltransferase, GCN5, or the SIRT1 inhibitor, nicotinamide, induces PGC-1alpha acetylation and decreases expression of PGC-1alpha target genes in myotubes. Consistent with a switch from glucose to fatty acid oxidation that occurs in nutrient deprivation states, SIRT1 is required for induction and maintenance of fatty acid oxidation in response to low glucose concentrations. Thus, we have identified SIRT1 as a functional regulator of PGC-1alpha that induces a metabolic gene transcription program of mitochondrial fatty acid oxidation. These results have implications for understanding selective nutrient adaptation and how it might impact lifespan or metabolic diseases such as obesity and diabetes. PMID- 17347649 TI - Mob as tumor suppressor is activated by Hippo kinase for growth inhibition in Drosophila. AB - Tissue growth and organ size are determined by coordinated cell proliferation and apoptosis in development. Recent studies have demonstrated that Hippo (Hpo) signaling plays a crucial role in coordinating these processes by restricting cell proliferation and promoting apoptosis. Here we provide evidence that the Mob as tumor suppressor protein, Mats, functions as a key component of the Hpo signaling pathway. We found that Mats associates with Hpo in a protein complex and is a target of the Hpo serine/threonine protein kinase. Mats phosphorylation by Hpo increases its affinity with Warts (Wts)/large tumor suppressor (Lats) serine/threonine protein kinase and ability to upregulate Wts catalytic activity to target downstream molecules such as Yorkie (Yki). Consistently, our epistatic analysis suggests that mats acts downstream of hpo. Coexpression analysis indicated that Mats can indeed potentiate Hpo-mediated growth inhibition in vivo. Our results support a model in which Mats is activated by Hpo through phosphorylation for growth inhibition, and this regulatory mechanism is conserved from flies to mammals. PMID- 17347650 TI - Post-phosphorylation prolyl isomerisation of gephyrin represents a mechanism to modulate glycine receptors function. AB - The microtubule binding protein gephyrin plays a prominent role in establishing and maintaining a high concentration of inhibitory glycine receptors juxtaposed to presynaptic releasing sites. Here, we show that endogenous gephyrin undergoes proline-directed phosphorylation, which is followed by the recruitment of the peptidyl-prolyl isomerase Pin1. The interaction between gephyrin and Pin1 is strictly dependent on gephyrin phosphorylation and requires serine-proline consensus sites encompassing the gephyrin proline-rich domain. Upon binding, Pin1 triggers conformational changes in the gephyrin molecule, thus enhancing its ability to bind the beta subunit of GlyRs. Consistently, a downregulation of GlyR clusters was detected in hippocampal neurons derived from Pin1 knockout mice, which was paralleled by a reduction in the amplitude of glycine-evoked currents. Our results suggest that phosphorylation-dependent prolyl isomerisation of gephyrin represents a mechanism for regulating GlyRs function. PMID- 17347651 TI - Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. AB - Autophagy is a major catabolic pathway by which eukaryotic cells degrade and recycle macromolecules and organelles. This pathway is activated under environmental stress conditions, during development and in various pathological situations. In this study, we describe the role of reactive oxygen species (ROS) as signaling molecules in starvation-induced autophagy. We show that starvation stimulates formation of ROS, specifically H(2)O(2). These oxidative conditions are essential for autophagy, as treatment with antioxidative agents abolished the formation of autophagosomes and the consequent degradation of proteins. Furthermore, we identify the cysteine protease HsAtg4 as a direct target for oxidation by H(2)O(2), and specify a cysteine residue located near the HsAtg4 catalytic site as a critical for this regulation. Expression of this regulatory mutant prevented the formation of autophagosomes in cells, thus providing a molecular mechanism for redox regulation of the autophagic process. PMID- 17347652 TI - Cytokinesis in yeast meiosis depends on the regulated removal of Ssp1p from the prospore membrane. AB - Intracellular budding is a developmentally regulated type of cell division common to many fungi and protists. In Saccaromyces cerevisiae, intracellular budding requires the de novo assembly of membranes, the prospore membranes (PSMs) and occurs during spore formation in meiosis. Ssp1p is a sporulation-specific protein that has previously been shown to localize to secretory vesicles and to recruit the leading edge protein coat (LEP coat) proteins to the opening of the PSM. Here, we show that Ssp1p is a multidomain protein with distinct domains important for PI(4,5)P(2) binding, binding to secretory vesicles and inhibition of vesicle fusion, interaction with LEP coat components and that it is subject to sumoylation and degradation. We found non-essential roles for Ssp1p on the level of vesicle transport and an essential function of Ssp1p to regulate the opening of the PSM. Together, our results indicate that Ssp1p has a domain architecture that resembles to some extent the septin class of proteins, and that the regulated removal of Ssp1p from the PSM is the major step underlying cytokinesis in yeast sporulation. PMID- 17347653 TI - Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription. AB - Fra-1 is frequently overexpressed in epithelial cancers and implicated in invasiveness. We previously showed that Fra-1 plays crucial roles in RAS transformation in rat thyroid cells and mouse fibroblasts. Here, we report a novel role for Fra-1 as a regulator of mitotic progression in RAS-transformed thyroid cells. Fra-1 expression and phosphorylation are regulated during the cell cycle, peaking at G2/M. Knockdown of Fra-1 caused a proliferative block and apoptosis. Although most Fra-1-knockdown cells accumulated in G2, a fraction of cells entering M-phase underwent abortive cell division and exhibited hallmarks of genomic instability (micronuclei, lagging chromosomes and anaphase bridges). Furthermore, we established a link between Fra-1 and the cell-cycle machinery by identifying cyclin A as a novel transcriptional target of Fra-1. During the cell cycle, Fra-1 was recruited to the cyclin A gene (ccna2) promoter, binding to previously unidentified AP-1 sites and the CRE. Fra-1 also induced the expression of JunB, which in turn interacts with the cyclin A promoter. Hence, Fra-1 induction is important in thyroid tumorigenesis, critically regulating cyclin expression and cell-cycle progression. PMID- 17347655 TI - Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics. AB - Rapid progress towards understanding the molecular underpinnings of neurodegenerative disorders such as Alzheimer's disease is revolutionizing drug discovery for these conditions. Furthermore, the development of models for these disorders is accelerating efforts to translate insights related to neurodegenerative mechanisms into disease-modifying therapies. However, there is an urgent need for biomarkers to diagnose neurodegenerative disorders early in their course, when therapy is likely to be most effective, and to monitor responses of patients to new therapies. As research related to this need is currently most advanced for Alzheimer's disease, this Review focuses on progress in the development and validation of biomarkers to improve the diagnosis and treatment of Alzheimer's disease and related disorders. PMID- 17347654 TI - CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. AB - Accumulated evidence indicates that progesterone receptors (PR) are involved in proliferation of breast cancer cells and are implicated in the development of breast cancer. In this paper, a yeast two-hybrid screen for PR led to the identification of CUE domain containing 2 (CUEDC2), whose function is unknown. Our results demonstrate that CUEDC2 interacts with PR and promotes progesterone induced PR degradation by the ubiquitin-proteasome pathway. The inhibition of endogenous CUEDC2 by siRNA nearly abrogated the progesterone-induced degradation of PR, suggesting that CUEDC2 is involved in progesterone-induced PR ubiquitination and degradation. Moreover, we identify the sumoylation site Lys 388 of PR as the target of CUEDC2-promoted ubiquitination. CUEDC2 decreases the sumoylation while promoting ubiquitination on Lys-388 of PRB. We also show that CUEDC2 represses PR transactivation, inhibits the ability of PR to stimulate rapid MAPK activity, and impairs the effect of progesterone on breast cancer cell growth. Therefore, our results identify a key post-translational mechanism that controls PR protein levels and for the first time provide an important insight into the function of CUEDC2 in breast cancer proliferation. PMID- 17347657 TI - Laparoscopic partial nephrectomy: an evolving standard. PMID- 17347658 TI - Prognostic factors in squamous cell carcinoma of the penis. AB - Squamous cell carcinoma (SCC) of the penis is an uncommon disease in the US and Europe. Without treatment, patients with penile SCC usually die within 2 years after diagnosis of the primary lesion, because of uncontrollable locoregional disease or from distant metastases. The spread of the tumor to the locoregional lymph nodes (lymph-node positivity) is the most relevant prognostic factor. With the available treatments, 5-year cancer-specific survival probabilities are between 75% and 93% for those patients with clinically node-negative disease, and progressively lower for those with increasingly extensive node-positive disease. Similarly, patients with pathologically proven negative nodes have 5-year cancer specific survival probabilities ranging from 85% to 100%. While patients with a single positive superficial lymph node on pathology have very good cancer-related outcomes, patients with multiple involved lymph nodes have significantly less favorable outcomes. This article focuses on the most important issues that surround the prognosis of squamous cell carcinoma of the penis, with special attention to the prognostic nomograms for penile cancer patients published in 2006. PMID- 17347659 TI - Quality-of-life assessment in patients with bladder cancer. AB - Health-related quality of life (HRQOL) in patients with bladder cancer is important, because radical cystectomy and urinary diversion significantly affect urinary and sexual function, and lead to associated sex-specific morbidity. This article reviews the current methods for defining HRQOL, describes the specific challenges in measuring HRQOL in patients with bladder cancer, and critically analyzes the existing literature on bladder cancer HRQOL. Previous studies have been limited by study design, generalizability, and by the different instruments used, namely nonvalidated questionnaires that are not specific for bladder cancer. To date, only two prospective studies with baseline HRQOL data have been published and few conclusions can be drawn from these cross-sectional, retrospective studies. On the basis of the published literature, there is no convincing evidence that superior HRQOL is achieved with a particular type of urinary diversion after cystectomy for bladder cancer. Patients should be counseled on all reconstructive alternatives and a diversion chosen on the basis of patient preference, patient anatomy and tumor status, rather than on a potential difference in HRQOL. Prospective studies with appropriate adjustment for confounding factors, which use validated and disease-specific questionnaires, are needed for HRQOL research on bladder cancer. PMID- 17347660 TI - Botulinum toxin for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. AB - Botulinum toxin (BTX) is the most potent biological toxin used for the treatment of urologic conditions. During the last 3 years, the use of BTX has been extended to the treatment of symptomatic benign prostatic hyperplasia, however, the actual mechanism through which BTX can reduce prostate volume and infravesical resistance is not well understood. This article reviews the main effects of BTX in prostate tissues. A critical analysis of the outcomes of patients who were studied in clinical series that used this toxin to treat lower urinary tract symptoms related to benign prostatic hyperplasia is also presented. PMID- 17347661 TI - Mechanisms of disease: pharmacogenetics of testosterone therapy in hypogonadal men. AB - A defective, mutated androgen receptor may lead to variable phenotypes of androgen insensitivity in humans. Also, the CAG repeat polymorphism in exon 1 of the androgen receptor gene modulates androgen effects; in vitro, transcription of androgen-dependent target genes is attenuated with increasing length of triplet residues. Clinically, the CAG repeat polymorphism causes significant modulations of androgenicity in various tissues and psychological traits in healthy eugonadal men: the longer the repeat tracts, the less pronounced is the androgen effect when individuals with similar testosterone concentrations are compared. Furthermore, as effects of testosterone substitution are markedly influenced by the number of CAG repeats, the pharmacogenetic implications of this polymorphism are likely to have a significant role in future testosterone treatment of hypogonadal men. Thresholds at which testosterone treatment should be initiated, as well as androgen dosage, might be tailored according to the receptor polymorphism. PMID- 17347662 TI - Lymphoepithelioma-like carcinoma of the urinary bladder--diagnostic and clinical implications. AB - BACKGROUND: A 57-year-old man presented with a 4-week history of intermittent, painless frank hematuria. There were no other symptoms. He had no previous urologic history, is a nonsmoker, and works as a manual laborer. INVESTIGATIONS: Physical examination, ultrasound of the urinary tract, and intravenous urography were all unremarkable. Urine microscopy confirmed more than 5 red blood cells per high-power field, but no malignant cells were seen on cytologic assessment. Flexible cystoscopy revealed a 3 cm, partially solid, solitary lesion on the right lateral wall of the bladder. The tumor was completely resected under general anesthesia. DIAGNOSIS: Histologically, the tumor was described as a G3 pT1 transitional cell carcinoma of the bladder. MANAGEMENT: Following the resection of a solitary recurrence 6 weeks after the initial tumor resection, the patient underwent a standard course of intravesical bacillus Calmette-Guerin therapy. Despite this, another tumor was identified 3 months later. Histologically, this tumor was described as a lymphoepithelioma-like carcinoma, of at least grade G3pT1. The patient underwent radical cystoprostatectomy with ileal conduit formation; no adjuvant systemic chemotherapy was given in light of complete tumor resection. The patient is under continuing, close clinical and radiologic observation and remains free of disease recurrence, 36 months postoperatively. PMID- 17347664 TI - The antiapoptotic activity of insect IAPs requires activation by an evolutionarily conserved mechanism. AB - Apoptosis represents a fundamental biological process that relies on the activation of caspases. Inhibitor of apoptosis (IAP) proteins represent a group of negative regulators of both caspases and cell death. The current model dictates that IAPs suppress apoptosis by blocking the catalytic pocket of effector caspases thereby preventing substrate entry. Here, we provide evolutionary evidence for the functional interplay between insect IAPs and the N end rule-associated ubiquitylation machinery in neutralising effector caspases and cell death. We find that IAPs require 'priming' in order to function as antiapoptotic molecules. Consistently, we demonstrate that the antiapoptotic activity of diverse insect IAPs is activated by effector caspases, providing the cell with a sensitive strategy to monitor and neutralise active caspases. Almost 300 million years of evolutionary selection pressure has preserved a caspase cleavage site in insect IAPs that, following processing by a caspase, exposes a binding motif for the N-end-rule-associated degradation machinery. Recruitment of this ubiquitylation machinery into the 'cleaved-IAP:caspase' complex provides a mechanism to negatively regulate effector caspases and block apoptosis. Furthermore, comparisons between cellular and several viral IAPs suggest differences in their modes of action, as OpIAP3, CpGV-IAP3 and HcNPV-IAP3 fail to associate with several effector caspases. Evolutionary conservation of the N-end rule degradation pathway in IAP-mediated regulation of apoptosis further corroborates the physiological relevance of this ubiquitylation-associated process. PMID- 17347663 TI - Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation. AB - Stromal stem cells from human dental pulp (SBP-DPSCs) were used to study osteogenic differentiation in vitro and in vivo. We previously reported that SBP DPSCs are multipotent stem cells able to differentiate into osteoblasts, which synthesize three-dimensional woven bone tissue chips in vitro. In this study, we followed the temporal expression pattern of specific markers in SBP-DPSCs and found that, when differentiating into osteoblasts, they express, besides osteocalcin, also flk-1 (VEGF-R2). In addition, 30% of them expressed specific antigens for endothelial cells, including CD54, von-Willebrand (domain 1 and 2), CD31 (PECAM-1) and angiotensin-converting enzyme. Interestingly, we found endotheliocytes forming vessel walls, observing that stem cells synergically differentiate into osteoblasts and endotheliocytes, and that flk-1 exerts a pivotal role in coupling osteoblast and endotheliocyte differentiation. When either SBP-DPSCs or bone chips obtained in vitro were transplanted into immunocompromised rats, they generated a tissue structure with an integral blood supply similar to that of human adult bone; in fact, a large number of HLA-1+ vessels were observed either within the bone or surrounding it in a periosteal layer. This study provides direct evidence to suggest that osteogenesis and angiogenesis mediated by human SBP-DPSCs may be regulated by distinct mechanisms, leading to the organization of adult bone tissue after stem cell transplantation. PMID- 17347665 TI - Poly(ADP-ribose) polymerase-1 protects neurons against apoptosis induced by oxidative stress. AB - In neurons, DNA is prone to free radical damage, although repair mechanisms preserve the genomic integrity. However, activation of the DNA repair system, poly(ADP-ribose) polymerase (PARP-1), is thought to cause neuronal death through NAD+ depletion and mitochondrial membrane potential (delta psi(m)) depolarization. Here, we show that abolishing PARP-1 activity in primary cortical neurons can either enhance or prevent apoptotic death, depending on the intensity of an oxidative stress. Only in severe oxidative stress does PARP-1 activation result in NAD+ and ATP depletion and neuronal death. To investigate the role of PARP-1 in an endogenous model of oxidative stress, we used an RNA interference (RNAi) strategy to specifically knock down glutamate-cysteine ligase (GCL), the rate-limiting enzyme of glutathione biosynthesis. GCL RNAi spontaneously elicited a mild type of oxidative stress that was enough to stimulate PARP-1 in a Ca2+ calmodulin kinase II-dependent manner. GCL RNAi-mediated PARP-1 activation facilitated DNA repair, although neurons underwent delta psi(m) loss followed by some apoptotic death. PARP-1 inhibition did not prevent delta psi(m) loss, but enhanced the vulnerability of neurons to apoptosis upon GCL silencing. Conversely, mild expression of PARP-1 partially prevented to GCL RNAi-dependent apoptosis. Thus, in the mild progressive damage likely occur in neurodegenerative diseases, PARP-1 activation plays a neuroprotective role that should be taken into account when considering therapeutic strategies. PMID- 17347666 TI - A novel form of ataxia oculomotor apraxia characterized by oxidative stress and apoptosis resistance. AB - Several different autosomal recessive genetic disorders characterized by ataxia with oculomotor apraxia (AOA) have been identified with the unifying feature of defective DNA damage recognition and/or repair. We describe here the characterization of a novel form of AOA showing increased sensitivity to agents that cause single-strand breaks (SSBs) in DNA but having no gross defect in the repair of these breaks. Evidence for the presence of residual SSBs in DNA was provided by dramatically increased levels of poly (ADP-ribose)polymerase (PARP-1) auto-poly (ADP-ribosyl)ation, the detection of increased levels of reactive oxygen/nitrogen species (ROS/RNS) and oxidative damage to DNA in the patient cells. There was also evidence for oxidative damage to proteins and lipids. Although these cells were hypersensitive to DNA damaging agents, the mode of death was not by apoptosis. These cells were also resistant to TRAIL-induced death. Consistent with these observations, failure to observe a decrease in mitochondrial membrane potential, reduced cytochrome c release and defective apoptosis-inducing factor translocation to the nucleus was observed. Apoptosis resistance and PARP-1 hyperactivation were overcome by incubating the patient's cells with antioxidants. These results provide evidence for a novel form of AOA characterized by sensitivity to DNA damaging agents, oxidative stress, PARP-1 hyperactivation but resistance to apoptosis. PMID- 17347667 TI - The nucleotide excision repair pathway is required for UV-C-induced apoptosis in Caenorhabditis elegans. AB - Ultraviolet (UV) radiation is a mutagen of major clinical importance in humans. UV-induced damage activates multiple signaling pathways, which initiate DNA repair, cell cycle arrest and apoptosis. To better understand these pathways, we studied the responses to UV-C light (254 nm) of germ cells in Caenorhabditis elegans. We found that UV activates the same cellular responses in worms as in mammalian cells. Both UV-induced apoptosis and cell cycle arrest were completely dependent on the p53 homolog CEP-1, the checkpoint proteins HUS-1 and CLK-2, and the checkpoint kinases CHK-2 and ATL-1 (the C. elegans homolog of ataxia telangiectasia and Rad3-related); ATM-1 (ataxia telangiectasia mutated-1) was also required, but only at low irradiation doses. Importantly, mutation of genes encoding nucleotide excision repair pathway components severely disrupted both apoptosis and cell cycle arrest, suggesting that these genes not only participate in repair, but also signal the presence of damage to downstream components of the UV response pathway that we delineate here. Our study suggests that whereas DNA damage response pathways are conserved in metazoans in their general outline, there is significant evolution in the relative importance of individual checkpoint genes in the response to specific types of DNA damage. PMID- 17347668 TI - KLF6 transcription factor protects hepatocellular carcinoma-derived cells from apoptosis. AB - Hepatocellular carcinoma (HCC) is a major public health concern because of the absence of early diagnosis and effective treatments. Efficient diagnosis modalities and therapies to treat HCC are needed. Kruppel-like factor (KLF) family members, such as KLF6, are involved in cell proliferation and differentiation. KLF6 is inactivated in solid tumors, which may contribute to pathogenesis. However, KLF6 status in HCC is controversial. Thus, we undertook the characterization of KLF6 expression and function in HCC and HCC-derived cell lines. We found that HCC, HepG2 and HuH7 cells expressed KLF6 messenger ribonucleic acid and protein. Next, using RNA interference, we demonstrated that inhibiting KLF6 expression in vitro strongly impaired cell proliferation-induced G1-phase arrest, inhibited cyclin-dependent kinase 4 and cyclin D1 expression, and subsequent retinoblastoma phosphorylation. Finally, KLF6 silencing caused p53 upregulation and inhibited Bcl-xL expression, to induce cell death by apoptosis. Taken together, these data demonstrated that KLF6 is essential for HCC-derived cells to evade apoptosis. PMID- 17347669 TI - Spliced-leader RNA silencing: a novel stress-induced mechanism in Trypanosoma brucei. AB - The signal-recognition particle (SRP) mediates the translocation of membrane and secretory proteins across the endoplasmic reticulum upon interaction with the SRP receptor. In trypanosomes, the main RNA molecule is the spliced-leader (SL) RNA, which donates the SL sequence to all messenger RNA through trans-splicing. Here, we show that RNA interference silencing of the SRP receptor (SRalpha) in Trypanosoma brucei caused the accumulation of SRP on ribosomes and triggered silencing of SL RNA (SLS). SLS was elicited due to the failure of the SL RNA specific transcription factor tSNAP42 to bind to its promoter. SL RNA reduction, in turn, eliminated mRNA processing and resulted in a significant reduction of all mRNA tested. SLS was also induced under pH stress and might function as a master regulator in trypanosomes. SLS is reminiscent of, but distinct from, the unfolded protein response and can potentially act as a new target for parasite eradication. PMID- 17347670 TI - Rapid activation of CLOCK by Ca2+-dependent protein kinase C mediates resetting of the mammalian circadian clock. AB - In mammals, immediate-early transcription of the Period 1 (Per1) gene is crucial for resetting the mammalian circadian clock. Here, we show that CLOCK is a real signalling molecule that mediates the serum-evoked rapid induction of Per1 in fibroblasts through the Ca2+-dependent protein kinase C (PKC) pathway. Stimulation with serum rapidly induced nuclear translocation, heterodimerization and Ser/Thr phosphorylation of CLOCK just before the surge of Per1 transcription. Serum-induced CLOCK phosphorylation was abolished by treatment with PKC inhibitors but not by other kinase inhibitors. Consistently, the interaction between CLOCK and PKC was markedly increased shortly after serum shock, and the Ca2+-dependent PKC isoforms PKCalpha and PKCgamma phosphorylated CLOCK in vitro. Furthermore, phorbol myristic acetate treatment triggered immediate-early transcription of Per1 and also CLOCK phosphorylation, which were blocked by a Ca2+-dependent PKC inhibitor. These findings indicate that CLOCK activation through the Ca2+-dependent PKC pathway might have a substantial role in phase resetting of the circadian clock. PMID- 17347671 TI - ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase. AB - It has been proposed that cell growth and autophagy are coordinated in response to cellular nutrient status, but the relationship between them is not fully understood. Here, we have characterized the fly mutants of Autophagy-specific gene 1 (ATG1), an autophagy-regulating kinase, and found that ATG1 is a negative regulator of the target of rapamycin (TOR)/S6 kinase (S6K) pathway. Our Drosophila studies have shown that ATG1 inhibits TOR/S6K-dependent cell growth and development by interfering with S6K activation. Consistently, overexpression of ATG1 in mammalian cells also markedly inhibits S6K in a kinase activity dependent manner, and short interfering RNA-mediated knockdown of ATG1 induces ectopic activation of S6K and S6 phosphorylation. Moreover, we demonstrated that ATG1 specifically inhibits S6K activity by blocking phosphorylation of S6K at Thr 389. Taken together, our genetic and biochemical results strongly indicate crosstalk between autophagy and cell growth regulation. PMID- 17347672 TI - Altered acetylcholine, bradykinin and cutaneous pressure-induced vasodilation in mice lacking the TREK1 potassium channel: the endothelial link. AB - The TWIK related K+ channel TREK1 is an important member of the class of two-pore domain K+ channels. It is a background K+ channel and is regulated by hormones, neurotransmitters, intracellular pH and mechanical stretch. This work shows that TREK1 is present both in mesenteric resistance arteries and in skin microvessels. It is particularly well expressed in endothelial cells. Deletion of TREK1 in mice leads to an important alteration in vasodilation of mesenteric arteries induced by acetylcholine and bradykinin. Iontophoretic delivery of acetylcholine and bradykinin in the skin of TREK1+/+ and TREK1-/- mice also shows the important role of TREK1 in cutaneous endothelium-dependent vasodilation. The vasodilator response to local pressure application is also markedly decreased in TREK1-/- mice, mimicking the decreased response to pressure observed in diabetes. Deletion of TREK1 is associated with a marked alteration in the efficacy of the G-protein coupled receptor-associated cascade producing NO that leads to major endothelial dysfunction. PMID- 17347674 TI - Dual role for Saccharomyces cerevisiae Tel1 in the checkpoint response to double strand breaks. AB - The main responder to DNA double-strand breaks (DSBs) in mammals is ataxia telangiectasia mutated (ATM), whereas DSB-induced checkpoint activation in budding yeast seems to depend primarily on the ATM and Rad-3-related (ATR) orthologue Mec1. Here, we show that Saccharomyces cerevisiae Tel1, the ATM orthologue, has two functions in checkpoint response to DSBs. First, Tel1 participates, together with the MRX complex, in Mec1-dependent DSB-induced checkpoint activation by increasing the efficiency of single-stranded DNA accumulation at the ends of DSBs, and this checkpoint function can be overcome by overproducing the exonuclease Exo1. Second, Tel1 can activate the checkpoint response to DSBs independently of Mec1, although its signalling activity only becomes apparent when several DSBs are generated. Furthermore, we provide evidence that the kinetics of DSB resection can influence Tel1 activation, indicating that processing of the DSB termini might influence the transition from Tel1/ATM- to Mec1/ATR-dependent checkpoint. PMID- 17347675 TI - A novel manoeuvre using a Kelly punch in the management of severe capsule contraction syndrome. PMID- 17347673 TI - Stra13 is induced by genotoxic stress and regulates ionizing-radiation-induced apoptosis. AB - In response to a number of genotoxic stimuli that induce DNA damage in cells, the tumour suppressor p53 is activated resulting in cell cycle arrest or apoptosis. In this study, we have identified stimulated with retinoic acid 13 (Stra13), a basic helix-loop-helix transcription factor, as a regulator of ionizing-radiation induced apoptosis. We show that Stra13 is induced in response to several DNA damaging agents in a p53-independent manner. Stra13-/- thymocytes show impaired apoptosis in response to ionizing radiation, and consistently, p53 levels and also expression of its key transcriptional targets Puma and Noxa are reduced in the mutant thymocytes. In vitro, Stra13 regulates p53 levels in a mouse double mutant 2 (Mdm2)-dependent manner by physically interacting with p53 and preventing Mdm2-mediated ubiquitination and nuclear export. Together, our studies provide evidence that Stra13 is involved in DNA-damage-induced apoptosis and indicate its role in tumorigenesis. PMID- 17347676 TI - Treatment of a vasoproliferative tumour with intravitreal bevacizumab (Avastin). PMID- 17347677 TI - Spontaneous resolution of retinal pigment epithelial tears and pigment epithelial detachment following blunt trauma. PMID- 17347678 TI - A British Ophthalmological Surveillance Unit study on serious ocular injuries from fireworks in the UK. AB - PURPOSE: We conducted a surveillance study to assess the nature, management, and visual outcomes of serious ocular injuries from fireworks in the UK. METHODS: New cases of serious ocular injuries from fireworks were prospectively ascertained through the monthly active surveillance system of the British Ophthalmological Surveillance Unit (BOSU). All ophthalmologists in the UK received a reporting card each month for a 2-year period commencing July 2004. They were asked to indicate any new cases of serious ocular injury from a firework, or to confirm that they had no new cases to report. Information on demographic detail, type of injury, management, and visual outcome was sought through an incident and 6-month follow-up questionnaire. RESULTS: Eighty-one per cent of the injuries occurred in October and November and 27% (13/47) of the patients were less than 18 years old. Twenty-six per cent (12/47) of patients had a penetrating injury, and ocular surgery was required in 53% (25/47) of cases. Eight patients (17%) required enucleation or evisceration and four (9%) required a cosmetic shell for phthisis. At 6-month follow-up, 53% (21/40) of cases had a visual acuity of 6/60 or worse. CONCLUSION: This prospective national survey confirms that firework injuries are an important cause of preventable visual disability particularly to young males. It is likely that such injuries occur year on year and as such represent an important public health concern in addition to the burden placed upon the health service. PMID- 17347679 TI - Capturing myopia and hypermetropia 'phenotypes' without formal refraction. AB - PURPOSE: Understanding genetic and environmental factors that together contribute to the development of myopia is an international research priority. We have investigated the feasibility and accuracy of identifying and classifying refractive error, without formal refraction, as a means of easily identifying affected individuals in a large-scale, non-ophthalmological, and population-based survey. METHODS: At age 44/45 years, members of the 1958 British birth cohort underwent a biomedical, community survey. Refractive error (autorefraction) was measured and categorised by spherical equivalent (SE) measurement; myopia (SE of 1.00 or more extreme), hypermetropia (+1.00 or more extreme), or emmetropia ( 0.99 to +0.99). Lenses of prescribed distance glasses, if worn, were assessed as minifying, magnifying, or making no difference to a standard viewed image and cohort members reported on 'short' or 'long' sightedness. RESULTS: A total of 2499 cohort members, randomly selected, had formal refraction (autorefraction) and 917 (36.7%) of these individuals had their prescribed distance glasses examined. Sensitivities for myopia and hypermetropia using examination of glasses were over 80% and positive predictive values were 95 and 65% respectively whereas self-report of 'short-sightedness' or 'long-sightedness' had poor accuracy. CONCLUSION: We suggest examination of prescribed distance glasses can be an effective method of 'screening' for refractive error in the field, especially where prevalence is high. PMID- 17347680 TI - Alpha antagonists and intraoperative floppy iris syndrome (IFIS) during trabeculectomy. PMID- 17347681 TI - Short-term efficacy of rofecoxib and diclofenac in acute shoulder pain: a placebo controlled randomized trial. AB - OBJECTIVES: To evaluate the short-term symptomatic efficacy of rofecoxib and diclofenac versus placebo in acute episodes of shoulder pain. DESIGN: Randomized controlled trial of 7 days. SETTING: Rheumatologists and/or general practitioners totaling 47. PARTICIPANTS: Acute shoulder pain. INTERVENTIONS: Rofecoxib 50 mg once daily, diclofenac 50 mg three times daily, and placebo. OUTCOME MEASURES: Pain, functional impairment, patient's global assessment of his/her disease activity, and local steroid injection requirement for persistent pain. The primary variable was the Kaplan-Meier estimates of the percentage of patients at day 7 fulfilling the definition of success (improvement in pain intensity and a low pain level sustained to the end of the 7 days of the study; log-rank test). RESULTS: There was no difference in the baseline characteristics between the three groups (rofecoxib n = 88, placebo n = 94, and diclofenac n = 89). At day 7, the Kaplan-Meier estimates of successful patients was higher in the treatment groups than in the placebo (54%, 56%, and 38% in the diclofenac, rofecoxib, and placebo groups respectively, p = 0.0070 and p = 0.0239 for placebo versus rofecoxib and diclofenac, respectively). During the 7 days of the study, there was a statistically significant difference between placebo and both active arms (rofecoxib and diclofenac) in all the evaluated outcome measures A local steroid injection had to be performed in 33 (35%) and 19 (22%) patients in the placebo and rofecoxib group respectively. Number needed to treat to avoid such rescue therapy was 7 patients (95% confidence interval 5-15). CONCLUSION: This study highlights the methodological aspects of clinical trials, e.g., eligibility criteria and outcome measures, in acute painful conditions. The data also establish that diclofenac and rofecoxib are effective therapies for the management of acute painful shoulder and that they reduce the requirement for local steroid injection. PMID- 17347682 TI - SPDEF regulates goblet cell hyperplasia in the airway epithelium. AB - Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo. PMID- 17347683 TI - A p53-derived apoptotic peptide derepresses p73 to cause tumor regression in vivo. AB - The tumor suppressor p53 is a potent inducer of tumor cell death, and strategies exist to exploit p53 for therapeutic gain. However, because about half of human cancers contain mutant p53, application of these strategies is restricted. p53 family members, in particular p73, are in many ways functional paralogs of p53, but are rarely mutated in cancer. Methods for specific activation of p73, however, remain to be elucidated. We describe here a minimal p53-derived apoptotic peptide that induced death in multiple cell types regardless of p53 status. While unable to activate gene expression directly, this peptide retained the capacity to bind iASPP - a common negative regulator of p53 family members. Concordantly, in p53-null cells, this peptide derepressed p73, causing p73 mediated gene activation and death. Moreover, systemic nanoparticle delivery of a transgene expressing this peptide caused tumor regression in vivo via p73. This study therefore heralds what we believe to be the first strategy to directly and selectively activate p73 therapeutically and may lead to the development of broadly applicable agents for the treatment of malignant disease. PMID- 17347684 TI - The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis. AB - The homeobox transcription factor CDX2 plays an important role in embryonic development and regulates the proliferation and differentiation of intestinal epithelial cells in the adult. We have found that CDX2 is expressed in leukemic cells of 90% of patients with acute myeloid leukemia (AML) but not in hematopoietic stem and progenitor cells derived from normal individuals. Stable knockdown of CDX2 expression by RNA interference inhibited the proliferation of various human AML cell lines and strongly reduced their clonogenic potential in vitro. Primary murine hematopoietic progenitor cells transduced with Cdx2 acquired serial replating activity, were able to be continuously propagated in liquid culture, generated fully penetrant and transplantable AML in BM transplant recipients, and displayed dysregulated expression of Hox family members in vitro and in vivo. These results demonstrate that aberrant expression of the developmental regulatory gene CDX2 in the adult hematopoietic compartment is a frequent event in the pathogenesis of AML; suggest a role for CDX2 as part of a common effector pathway that promotes the proliferative capacity and self-renewal potential of myeloid progenitor cells; and support the hypothesis that CDX2 is responsible, in part, for the altered HOX gene expression that is observed in most cases of AML. PMID- 17347685 TI - Deficiency of Src homology 2 domain-containing inositol 5-phosphatase 1 affects platelet responses and thrombus growth. AB - Platelets are critical for normal hemostasis. Their deregulation can lead to bleeding or to arterial thrombosis, a primary cause of heart attack and ischemic stroke. Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is a 5 phosphatase capable of dephosphorylating the phosphatidylinositol 3,4,5 trisphosphate second messenger into phosphatidylinositol 3,4-bisphosphate. SHIP1 plays a critical role in regulating the level of these 2 lipids in platelets. Using SHIP1-deficient mice, we found that its loss affects platelet aggregation in response to several agonists with minor effects on fibrinogen binding and beta(3) integrin tyrosine phosphorylation. Accordingly, SHIP1-null mice showed defects in arterial thrombus formation in response to a localized laser-induced injury. Moreover, these mice had a prolonged tail bleeding time. Upon stimulation, SHIP1-deficient platelets showed large membrane extensions, abnormalities in the open canalicular system, and a dramatic decrease in close cell-cell contacts. Interestingly, SHIP1 appeared to be required for platelet contractility, thrombus organization, and fibrin clot retraction. These data indicate that SHIP1 is an important element of the platelet signaling machinery to support normal hemostasis. To our knowledge, this is the first report unraveling an important function of SHIP1 in the activation of hematopoietic cells, in contrast to its well-documented role in the negative regulation of lymphocytes. PMID- 17347686 TI - Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. AB - The origin and turnover of connective tissue cells in adult human organs, including the lung, are not well understood. Here, studies of cells derived from human lung allografts demonstrate the presence of a multipotent mesenchymal cell population, which is locally resident in the human adult lung and has extended life span in vivo. Examination of plastic-adherent cell populations in bronchoalveolar lavage samples obtained from 76 human lung transplant recipients revealed clonal proliferation of fibroblast-like cells in 62% (106 of 172) of samples. Immunophenotyping of these isolated cells demonstrated expression of vimentin and prolyl-4-hydroxylase, indicating a mesenchymal phenotype. Multiparametric flow cytometric analyses revealed expression of cell-surface proteins, CD73, CD90, and CD105, commonly found on mesenchymal stem cells (MSCs). Hematopoietic lineage markers CD14, CD34, and CD45 were absent. Multipotency of these cells was demonstrated by their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. Cytogenetic analysis of cells from 7 sex-mismatched lung transplant recipients harvested up to 11 years after transplant revealed that 97.2% +/- 2.1% expressed the sex genotype of the donor. The presence of MSCs of donor sex identity in lung allografts even years after transplantation provides what we believe to be the first evidence for connective tissue cell progenitors that reside locally within a postnatal, nonhematopoietic organ. PMID- 17347687 TI - The life and hard times of a coronary surgeon. AB - Coronary artery bypass is arguably the most extensively studied operation in surgical history. The technical advances and beneficial effects on symptoms and prognosis have been well documented over four decades. Percutaneous coronary interventions (PCIs) have also evolved through numerous modifications, and symptom relief has been substantiated; both modalities have been challenged by many randomized controlled trials. The rapid growth of PCIs has decreased coronary artery bypass volumes, and resulted in concerns about training, teaching, research, jobs and income. The most important concern, however, is the increasing 'off-label' application of PCIs with drug-eluting stents to a variety of untested coronary lesions. The randomized controlled trials studied a small fraction of those registered and excluded patients who are known to benefit from surgery and, thus, these studies were inherently biased. The results were then extrapolated to 'real-world' patients, who had been misinformed and misled about the performance and prognosis of coronary stents, as was later revealed in various registries. Hospitals should develop a collaborative revascularization strategy to provide patients and families with realistic alternatives. PMID- 17347688 TI - Should cholesterol-lowering medications be available in Canada without a prescription? AB - Cardiovascular disease (CVD) presents an enormous and growing burden on the Canadian health care system. Elevated serum low-density lipoprotein cholesterol levels are an established, major risk factor in the development of premature CVD. There is strong evidence that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, significantly lower both low-density lipoprotein cholesterol levels and CVD risk. However, there is currently a treatment gap, in that a large segment of the population who should be receiving statins due to elevated serum cholesterol levels are not. Individuals at moderate risk of developing CVD represent one large population segment that is currently being undertreated. This group may be a candidate for receiving over-the-counter (OTC) or behind-the-counter (BTC) statins, which may be a suitable primary prevention strategy. Nonetheless, it must be noted that hypercholesterolemia is a complex, chronic condition that must be carefully managed and requires close consultation with a health care practitioner. The advantages and disadvantages of OTC or BTC statin usage must therefore be carefully weighed before any potential introduction of OTC or BTC statins in Canada. PMID- 17347689 TI - Newborn hearts are at greater 'metabolic risk' during global ischemia--advantages of continuous coronary washout. AB - BACKGROUND: Altered metabolic responses of the newborn heart to ischemia, which may increase irreversible injury, may at least partially explain the greater morbidity and mortality experienced by some children undergoing congenital cardiac repair. The present study compared newborn heart metabolic responses to global ischemia with those of adult, and evaluated whether continuous coronary artery washout in the newborn heart during 'ischemia' could favourably affect these responses. METHODS: Adult (n=12) and newborn (n=12) pigs were anesthetized, and right ventricular biopsies were taken before global ischemia and at set intervals during ischemia. Another 12 newborns were subdivided into groups of nonperfused hearts and hearts receiving continuous perfusion. Time to onset of and time to peak of ischemic contracture were recorded. Biopsies were assayed for lactate, myocardial glycogen, glucose-6-phosphate and ATP. RESULTS: Newborn hearts were more sensitive to global ischemia than adult hearts, based on shorter time to onset of and time to peak of ischemic contracture, and had a significantly greater rate of ATP decline (P<0.01). This was due in part to a more rapid accumulation of lactate (P<0.05) and only a 50% use of glycogen, compared with 93% by adult hearts. Continuous washout of newborn hearts prevented lactate accumulation, allowing a 90% use of glycogen and delaying time to ischemic contracture by twofold. This was accompanied by lower levels of glucose 6-phosphate accumulation (P<0.05) and a threefold reduction in the rate of ATP decline. CONCLUSIONS: Significant differences in myocardial metabolism during ischemia in newborns compared with adults could predispose them to earlier ischemic injury, which can be eliminated by the removal of end products. Perfusion strategies taking these differences into account may further optimize pediatric myocardial protection and improve outcomes in newborn children undergoing cardiac procedures. PMID- 17347690 TI - The effect of acetylsalicylic acid resistance on prognosis of patients who have developed acute coronary syndrome during acetylsalicylic acid therapy. AB - AIM: The relationships between clinical events and acetylsalicylic acid resistance (AR), as well as its frequency, have been established in stable patients with coronary artery disease (CAD). Although acute coronary syndrome (ACS) patients taking acetylsalicylic acid have been accepted as a high-risk population, the role of AR has not been investigated in these patient groups. Thus, in the present study, the impact of AR was investigated in patients with ACS who were taking acetylsalicylic acid. METHODS: Between January 2001 and February 2003, 140 ACS patients were included in the present prospective study. All patients had ACS while taking acetylsalicylic acid. Coronary angiographic scores for severity and extent of CAD were determined for all patients. The effect of acetylsalicylic acid on platelet function was assessed by the platelet function analyzer PFA-100 (Dade Behring, USA). The primary end point was the composite of death, myocardial infarction, cerebrovascular accident and revascularization. The mean follow-up period was 20 months. RESULTS: Patients with AR were older than patients without AR (63.8+/-10.8 years versus 58.3+/-11.2 years; P=0.005). Moreover, myocardial damage was higher in patients with AR according to cardiac troponin T values (1.11+/-1.3 mug/L versus 0.41+/-0.5 mug/L; P=0.01). The composite end point of death, myocardial infarction, cerebrovascular accident or revascularization was present in 16 of 45 patients (35%) with AR and in 13 of 79 patients (16%) without AR (hazard ratio 2.46, 95% CI 1.18 to 5.13; P=0.016). After adjustment for age, platelet count, cardiac troponin T value and CAD severity score, AR remained an independent predictor for long-term adverse events (hazard ratio 3.03, 95% CI 1.06 to 8.62; P=0.038). CONCLUSIONS: The clinical event rate was found to be higher in ACS patients with AR than in those without AR. Thus, it may be concluded that there is a strong correlation between a worse prognosis and AR in these patients. PMID- 17347691 TI - Acetylsalicylic acid resistance and clinical outcome--the Hobikoglu study is worth noting. PMID- 17347692 TI - Mitral regurgitation: determinants of referral for cardiac surgery by Canadian cardiologists. AB - PURPOSE: Advances in surgery permit for earlier intervention with improved outcomes for patients with mitral regurgitation (MR). Many patients still appear to be referred to surgery late in their course. Consensus guidelines were compared with the surgical referral practices for MR among Canadian cardiologists. METHODS: A self-administered questionnaire was mailed to all adult cardiologists in Canada. This included seven case scenarios, as well as direct questions designed to establish the influence of factors including atrial fibrillation, pulmonary hypertension, left ventricular (LV) dilation, experience of the cardiac surgeon, symptoms and ejection fraction (EF) on referral. RESULTS: There were 319 respondents; LVEF was rated as extremely important in 71.5% of patients and moderately important in 26% of patients. In asymptomatic patients, EF of 50% to 60% was correctly identified as a trigger for surgery by 57.2 % of cardiologists, while only 15.6% of cardiologists correctly referred New York Heart Association class II patients with normal LV function. The group complied in only 4.77 of the seven case scenarios. Compliance was inversely related to years in practice for asymptomatic patients with mild LV dysfunction, as well as in overall compliance. Referral practices were similar among clinicians, echocardiographers, interventional cardiologists and researchers, with no differences in geographic region or academic affiliation. CONCLUSION: Compliance with published guidelines for patients with MR and either New York Heart Association class II or mild LV dysfunction among Canadian cardiologists was poor. Compliance was somewhat better in more recent graduates, suggesting the need to institute programs geared at enhancing knowledge of published standards and introduce practical tools to aid in their implementation. PMID- 17347693 TI - Are patients with mitral regurgitation being referred too late for surgery? PMID- 17347694 TI - Intravascular volume dependency of left ventricular mass calculation by two dimensional guided M-mode echocardiography. AB - BACKGROUND: Increased left ventricular mass (LVM) is an independent risk factor for cardiovascular morbidity and mortality, and may be used for risk stratification. Two-dimensional echocardiography, the most commonly used technique for estimation of LVM, uses the third power of the left ventricular internal diameter (LVID) for the calculation. OBJECTIVES: To determine whether a decrease in intravascular volume after dialysis may cause inaccurate estimation of LVM by echocardiography. METHODS: Thirty-eight patients undergoing hemodialysis due to chronic renal failure constituted the study group (14 women [37%] and 24 men [63%], mean age +/- SD 38.7+/-10.9 years). LVID, and interventricular and posterior wall thicknesses were measured by two dimensionally guided M-mode echocardiography. Stroke volume and cardiac output were calculated using left ventricular outflow tract diameter and the pulsed-wave Doppler time-velocity integral obtained from left ventricular outflow tract. LVM was calculated by using Devereux's formula, and was indexed for body surface area and height. All echocardiographic parameters were measured or calculated before and after dialysis (on the same day), and then compared. RESULTS: There were no significant changes in wall thickness; however, LVID, LVM, the LVM/body surface index and the LVM/height index significantly decreased after dialysis (P<0.001 for each parameter). There was a significant correlation between the change in LVID and the change in LVM (P<0.001, r=0.59). Stroke volume and cardiac output also decreased significantly after hemodialysis (P<0.001 for each parameter). CONCLUSIONS: Intravascular volume-dependent change in LVID causes inaccurate estimation of LVM, so volume status should be kept in mind, especially in serial assessment of LVM. PMID- 17347695 TI - Valve surgery in octogenarians: in-hospital and long-term outcomes. AB - BACKGROUND: Global population aging and greater age-related incidence of ischemic, degenerative and calcific valve disease have led to an increasing number of very elderly patients being referred for valve surgery. However, their preoperative risk factors, and in-hospital and long-term outcomes have not been thoroughly investigated. METHODS: Three hundred seven consecutive patients 80 years and older (60% female; mean age 83+/-2.4 years) attending three major Italian cardiac centres to undergo valve surgery were evaluated. Seventy-nine patients underwent mitral valve surgery (isolated n=30, combined n=49) and 228 underwent aortic valve surgery (isolated n=134, combined n=94). RESULTS: The most frequent in-hospital complications were atrial arrhythmias, need for inotropic support for more than 48 h, renal insufficiency, congestive heart failure, respiratory failure, and stroke or transient ischemic attack. The in-hospital mortality rate was 9.7% (30 of 307). Multivariate logistic regression identified the following clinical variables as predictors of in-hospital death: New York Heart Association functional class IV, diabetes, hypertension, renal insufficiency at presentation, rheumatic etiology and left ventricular ejection fraction of less than 45%. Late mortality occurred in 45 of 277 patients (16.2%), but there was a substantial improvement in the New York Heart Association functional class of the 232 long-term survivors (from 3.0+/-0.7 to 1.7+/-0.6; P<0.0001). CONCLUSIONS: Surgery seems to be an effective therapeutic option for selected symptomatic octogenarians with valve disease, associated with good long term survival and an improved functional class. Operative mortality is related more to patients' preoperative clinical status and increased comorbidity than the type of surgery per se. PMID- 17347696 TI - Lithium-induced sinus node disease at therapeutic concentrations: linking lithium induced blockade of sodium channels to impaired pacemaker activity. AB - The present report describes a case of sinus node arrest in a manic-depressive patient being treated with lithium carbonate with a therapeutic serum level of lithium. A permanent rate-modulated ventricular pacemaker was inserted and lithium therapy was continued. A review of literature revealed several other similar case reports in which both therapeutic and toxic levels of serum lithium levels were associated with sinus node dysfunction and bradyarrhythmias. Because lithium is a potent blocker of cardiac sodium channels, and given the critical importance of sodium channels in pacemaker activity, lithium-induced sodium channel blockade is likely an important mechanism in sinus node dysfunction. PMID- 17347697 TI - Bioprosthetic valve degeneration due to cholesterol deposition in a patient with normal lipid profile. AB - Hypercholesterolemia has been identified as a risk factor for bioprosthetic valvular degeneration, and it has been suggested that statin therapy reduces this risk. The case of a 77-year-old man with low levels of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B who developed marked LDL-C crystal deposition and a severe foreign body giant cell reaction 21.5 years after aortic bioprosthetic replacement is reported. This observation confirms that cholesterol deposition contributes to bioprosthetic valve degeneration, but that this can occur even in patients with low levels of LDL-C. It suggests that the characteristics of the valve are more critical than the patient's level of LDL-C. PMID- 17347698 TI - Endomyocardial fibrosis and hepatocellular carcinoma in Inhambane Province in Mozambique. PMID- 17347700 TI - Studying disorder in graphite-based systems by Raman spectroscopy. AB - Raman spectroscopy has historically played an important role in the structural characterization of graphitic materials, in particular providing valuable information about defects, stacking of the graphene layers and the finite sizes of the crystallites parallel and perpendicular to the hexagonal axis. Here we review the defect-induced Raman spectra of graphitic materials from both experimental and theoretical standpoints and we present recent Raman results on nanographites and graphenes. The disorder-induced D and D' Raman features, as well as the G'-band (the overtone of the D-band which is always observed in defect-free samples), are discussed in terms of the double-resonance (DR) Raman process, involving phonons within the interior of the 1st Brillouin zone of graphite and defects. In this review, experimental results for the D, D' and G' bands obtained with different laser lines, and in samples with different crystallite sizes and different types of defects are presented and discussed. We also present recent advances that made possible the development of Raman scattering as a tool for very accurate structural analysis of nano-graphite, with the establishment of an empirical formula for the in- and out-of-plane crystalline size and even fancier Raman-based information, such as for the atomic structure at graphite edges, and the identification of single versus multi graphene layers. Once established, this knowledge provides a powerful machinery to understand newer forms of sp(2) carbon materials, such as the recently developed pitch-based graphitic foams. Results for the calculated Raman intensity of the disorder-induced D-band in graphitic materials as a function of both the excitation laser energy (E(laser)) and the in-plane size (L(a)) of nano-graphites are presented and compared with experimental results. The status of this research area is assessed, and opportunities for future work are identified. PMID- 17347701 TI - Thrombin allostery. AB - Thrombin is a Na(+)-activated, allosteric serine protease that plays multiple functional roles in blood pathophysiology. Binding of Na(+) is the major driving force behind the procoagulant, prothrombotic and signaling functions of the enzyme. This review summarizes our current understanding of the molecular basis of thrombin allostery with special emphasis on the kinetic aspects of Na(+) activation. The molecular mechanism of thrombin allostery is a remarkable example of long-range communication that offers a paradigm for many other biological systems. PMID- 17347702 TI - Crossed beam studies of radical-radical reactions: O(3P) + C3H5 (allyl). AB - The dynamics of the radical-radical reaction O((3)P) + C(3)H(5) has been investigated by means of the crossed molecular beam technique with mass spectrometric detection at a collision energy of 73.0 kJ mol(-1); the reaction mechanism of the H-displacement channel has been elucidated, while experimental evidence of the occurrence of one or more C-C bond-breaking channels at this collision energy has been obtained. PMID- 17347703 TI - Weak distance dependence of through-bond interactions in tetrahydro-4H-thiopyran 4-ylidene end-capped oligo(cyclohexylidenes); a computational survey. AB - Calculations on members of the oligo(cyclohexylidene) series [(n), n = 1-5)] and related tetrahydro-4H-thiopyran end-capped analogues [(n), n = 1-4)] show a strong through-bond coupling between their pi bonds and sulfur lone pairs (Lp(pi)S). This coupling is mediated by an interaction between the H(ax)-C-C H(ax) structural sub-units and the pi bonds connecting the cyclohexyl moieties. A comparison of the length dependency of the through-bond coupling via an oligo(cyclohexylidene) and an alkane bridge [divinyl alkanes (n)] shows that oligo(cyclohexylidenes) are more efficient in mediating through-bond couplings over large distances. Oligo(cyclohexylidene) bridges exhibit molecular wire characteristics. PMID- 17347704 TI - The dynamics of water exchange in gadolinium DOTA complexes studied by transition path sampling and potential of mean force methods. AB - The mechanism of water exchange at the Gd centre of the two isomers of [Gd(iii)DOTA](-) (gadolinate(1-), [1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraacetato(4-)-N1,N4,N7,N10,O1,O4,O7,O10]) has been explored using transition path sampling and potential of mean force methods to sample those regions of phase space inaccessible to standard molecular dynamics simulation. We find that there are definite differences in the details of the solvent rearrangement accompanying the exchange of the capping water molecule for the two isomers. We conclude that these solvent effects, rather than any differences in the binding energy of the capping water, are central in determining the exchange rate. We find that the potential of mean force studies yield absolute and relative rates of water exchange for the two isomers that are in good agreement with experiment. PMID- 17347705 TI - Rotational spectrum of a chiral alpha-hydroxyester: conformation stability and internal rotation barrier heights of methyl lactate. AB - High resolution spectrum of methyl lactate, a chiral alpha-hydroxyester, has been investigated using a molecular jet Fourier transform microwave spectrometer. High level ab initio calculations were employed to study the conformational isomerism of methyl lactate. The observed rotational spectrum confirms that the most stable conformer has an intramolecular hydrogen bond of OH...O==C type, as predicted by the ab initio calculations. The internal rotation barrier heights of the ester methyl group and the alpha-carbon methyl group were calculated to be 5.4 and 14.5 kJ mol(-1) at the MP2/aug-cc-pVDZ level of theory for the most stable conformer. The internal rotation splittings due to the ester methyl group were observed and analyzed and the ester methyl group tunneling barrier height was determined experimentally to be 4.762 (3) kJ mol(-1). PMID- 17347706 TI - Radiation effects, energy storage and its release in solid rare gases. AB - An irradiation of solid argon sample by electrons ionizes the Ar atoms, and part of the beam energy is stored in the solid mainly in the form of self-trapped Ar(2)(+) holes. The pre-irradiated samples are investigated by methods of the so called "activation spectroscopy". During their controlled warm-up three thermally stimulated effects are observed and, in our experiments, simultaneously monitored: a VUV emission resulting from neutralization of the Ar(2)(+) holes by electrons, an anomalous desorption of surface atoms, and an exoelectron emission. A comparison of experiments with linear and step-wise sample heating shows clearly that all three processes are intimately connected. The heating detraps electrons, which neutralize the Ar(2)(+) holes resulting in a bound-free emission of argon dimers, centered around 9.7 eV. The excess energy set free during this process may dislodge surface atoms leading to an anomalous, low temperature, pressure rise. Some of the electrons can also be directly extracted from the sample and detected as an exoelectron current. The experiments provide information about the depth of electron traps, and indicate that there is a nearly continuous distribution of trapping energies. PMID- 17347707 TI - Formation of mesoscopic water networks in aqueous systems. AB - Formation of the macroscopically-infinite hydrogen-bonded water network in various aqueous systems occurs via 3D percolation transition when the probability of finding a spanning water cluster exceeds 95%. As a result, in a wide interval of water content below the percolation threshold, rarefied quasi-2D water networks span over the mesoscopic length scale. Formation and topology of spanning water networks, which affect various properties of aqueous systems, can be described within the framework of the percolation theory. PMID- 17347708 TI - Particle size dependent adsorption and reaction kinetics on reduced and partially oxidized Pd nanoparticles. AB - Combining scanning tunneling microscopy (STM), IR reflection absorption spectroscopy (IRAS) and molecular beam (MB) techniques, we have investigated particle size effects on a Pd/Fe(3)O(4) model catalyst. We focus on the particle size dependence of (i) CO adsorption, (ii) oxygen adsorption and (iii) Pd nanoparticle oxidation/reduction. The model system, which is based on Pd nanoparticles supported on an ordered Fe(3)O(4) film on Pt(111), is characterized in detail with respect to particle morphology, nucleation, growth and coalescence behavior of the Pd particles. Morphological changes upon stabilization by thermal treatment in oxygen atmosphere are also considered. The size of the Pd particles can be varied roughly between 1 and 100 nm. The growth and morphology of the Pd particles on the Fe(3)O(4)/Pt(111) film were characterized by STM and IRAS of adsorbed CO as a probe molecule. It was found that very small Pd particles on Fe(3)O(4) show a strongly modified adsorption behavior, characterized by atypically weak CO adsorption and a characteristic CO stretching frequency around 2130 cm(-1). This modification is attributed to a strong interaction with the support. Additionally, the kinetics of CO adsorption was studied by sticking coefficient experiments as a function of particle size. For small particles it is shown that the CO adsorption rate is significantly enhanced by the capture zone effect. The absolute size of the capture zone was quantified on the basis of the STM and sticking coefficient data. Finally, oxygen adsorption was studied by means of MB CO titration experiments. Pure chemisorption of oxygen is observed at 400 K, whereas at 500 K partial oxidation of the particles occurs. The oxidation behavior reveals strong kinetic hindrances to oxidation for larger particles, whereas facile oxidation and reduction are observed for smaller particles. For the latter, estimates point to the formation of oxide layers which, on average, are thicker than the surface oxides on corresponding single crystal surfaces. PMID- 17347709 TI - Suppression of aqueous surface hydrolysis by monolayers of short chain organic amphiphiles. AB - Aqueous aerosols and other water surfaces in the environment may be coated with organic films, which can give rise to significant effects on gas-solution transport and surface reactivity. We have used acridine as a molecular fluorescent pH probe to examine the hydration of nitric acid and ammonia at both the uncoated and the organic-coated air-water interface. For uncoated samples, a transient decrease in pH is observed at the interface upon introduction of nitric acid vapour, followed by a relaxation to a final pH which is lower than the initial value. This long-time final change in pH is also measured in bulk pH measurements. Solutions having monolayer and sub-monolayer films of 1-octanol do not display the transient, but do show the same long-time change in pH. The degree of suppression of the surface pH transient depends directly on the amount of octanol present at the surface. Hydrolysis of ammonia at the water surface is also indicated by a surface pH transient which is also suppressed when a monolayer of octanol is present at the surface. Monolayers of butanol and of uncompressed stearic acid at the surface show little difference from the clean interface. The results are related to the concentration of available water at the interface. PMID- 17347710 TI - Dynamics of short as compared with long poly(acrylic acid) chains hydrophobically modified with pyrene, as followed by fluorescence techniques. AB - New low and high molecular weight poly(acrylic acid), PAA, 2000 g mol(-1) and 450,000 g mol(-1), respectively, were tagged with pyrene (low and high contents of probe) and its behaviour in solution was investigated using absorption and fluorescence (steady-state and time-resolved) techniques. Fluorescence data shows that the degree and level of intramolecular association strongly depends on the molecular weight. With the short pyrene-labeled PAA chains in aqueous solution, the excimer-to-monomer fluorescence ratio I(E)/I(M) decreases with the increase of pH, oppositely to the increase in the I(E)/I(M) ratio with the increase in pH previously observed with the long chain PAA. Time-resolved data suggest that excimer formation with the short pyrene-labeled PAA polymers (ca. 28 acrylic acid monomers per chain) in water is largely due to excitation of Ground State Dimers, GSD. The increment of pH, and the consequent gradual ionization of the carboxylic groups in the chain, initially increases the fraction of GSD, possibly due to the occurrence of special micelle-like chain conformations, inside which the pyrene units are accommodated. A further increase of the pH above the pK(a) values, resulting in the full ionization of carboxylic groups, apparently destabilizes such chain conformations, which leads to a pH effect on the photophysical properties identical to that of the long chain polymers. In water, the dynamic data shows the existence of two excimers coexisting with two monomer classes. In methanol and dioxane (good solvents for the pyrene probe) at room temperature, where one excimer and two monomers are present, all rate constants could be obtained, as well as the fractions of ground-state species. It is thus shown that different types of interactions are produced with small- and long-sized PAA polymers, i.e., the size of the polymer matters. PMID- 17347711 TI - Benzene-o-dithiolate ligands as versatile building blocks in supramolecular chemistry. AB - Polydentate ligands with benzene-o-dithiolato donor groups are useful building blocks in supramolecular coordination chemistry. The coordination chemistry of bis- and tris(benzene-o-dithiolato) ligands and mixed benzene-o dithiolato/catecholato ligands is reviewed. These ligands exhibit a versatile coordination chemistry both in solution and in the solid state. PMID- 17347712 TI - Four quadruple metal-metal bonds lined up: linear nonachromium(II) metal string complexes. AB - Through a new pyrazine-modulated penta-pyridyl-tetraamine ligand, H(4)N(9)-mpz, linear nonachromium(II) complexes with four quadruple metal-metal bonds were successfully obtained, and their structure, magnetic and electrochemistry properties were studied. PMID- 17347713 TI - Clathrates with mixed guests. AB - Investigation of the selectivities of two diol organic hosts for pairs of small organic guests gave interesting results which could be correlated with the crystal structures of the inclusion compounds containing mixtures of the two guests; these structures were compared with those of the single guest inclusion compounds. PMID- 17347714 TI - A pillared layer MOF with anion-tunable magnetic properties and photochemical [2 + 2] cycloaddition. AB - A magnetic MOF with two distinct functions was prepared and characterized: [2 + 2] photodimerization and anti-ferro-magnetism with a well-pronounced anion tunable spin-flop transition below 2.5 K were both observed. PMID- 17347715 TI - Nucleo-copolymers: oligonucleotide-based amphiphilic diblock copolymers. AB - For the first time, poly(butadiene) has been covalently linked to an oligonucleotide sequence and the resulting nucleo-copolymer exhibits amphiphilic properties in dilute aqueous solution, self-assembling into nanometer-sized vesicular structures. PMID- 17347716 TI - Fluoride ion complexation by a cationic borane in aqueous solution. AB - The phosphonium borane [p-Mes(2)B(C(6)H(4))PMePh(2)](+) complexes fluoride in water containing 10% methanol with a binding constant of 1.0(+/-0.1) x 10(3) M( 1) to afford the zwitterion p-Mes(2)FB(C(6)H(4))PMePh(2). PMID- 17347717 TI - Di-pyrrolyl-pyrazoles: anion receptors in protonated form and efficient building blocks for organized structures. AB - Synthesis of di-pyrrolyl-substituted pyrazoles (dpp) and anion binding studies in protonated form are reported. Dpp show [2 + 2] binding of trifluoroacetate in the solid state to afford nanometer- and micrometer-scale architectures. PMID- 17347718 TI - Oxygenation vs iodonio substitution during the reactions of alkenyl-silanes with iodosylbenzene: participation of the internal oxy group. AB - Reaction of 4-acyl-oxy-but-1-enyl-silanes with iodosylbenzene in the presence of BF(3) x OEt(2) gave 4-acyloxy-2-oxobutyl-silane and 3-acyloxy-tetrahydrofuran-2 yl-silane via a 1,3-di-oxan-2-yl cation intermediate, which is generated by participation of the acyloxy group during the electrophilic addition of iodine(III) to the substrate. PMID- 17347719 TI - Application of nanoparticles for the enhancement of latent fingerprints. AB - Two different types of nanoparticles dissolved in organic solution, gold stabilized by n-alkanethiols and CdSe/ZnS stabilized by n-alkane-amine, adhere preferentially to the ridges of latent fingerprints; the gold deposits catalyze silver electroless deposition from "Silver Physical Developer" (Ag-PD), an aqueous solution containing silver colloids stabilized by cationic surfactants, to form dark impressions of the ridge details; the hydrophobic capped gold nanoparticles significantly improve the intensity and clarity of the developed prints compared with Ag-PD alone; finger marks treated with CdSe/ZnS nanoparticles can be viewed directly, due to their fluorescence under UV illumination. PMID- 17347720 TI - Isolating fluorinated carbocations. AB - Using carboranes as counterions, fluorinated benzyl-type carbocations such as (p FC(6)H(4))(2)CF(+), (p-FC(6)H(4))(CH(3))CF(+) and fluorinated trityl ions are readily isolated for X-ray and IR structural characterization. PMID- 17347721 TI - Metallacrown-based compartments: selective encapsulation of three isonicotinate anions in non-centrosymmetric solids. AB - Upon crystallization in high yields, metallacrowns form compartments that are capable of asymmetrically encapsulating three isonicotinate guests. PMID- 17347722 TI - A rationally designed macrocyclic cavitand that kills bacteria with high efficacy and good selectivity. AB - An amphiphilic macrocyclic cavitand that shows good antibacterial activity, comparable to that of peptide-based antibiotics was developed by rational design and its antibacterial selectivity over mammalian cells was examined. PMID- 17347723 TI - DNA hybridization "turns on" electro-catalysis at gold electrodes. AB - The efficiency of electro-catalysis occurring at DNA-modified gold electrodes is highly dependently on the density of DNA monolayers, as a result, DNA hybridization can "turn on" electro-catalysis by increasing the DNA surface density. PMID- 17347724 TI - Synthesis and reactivity of alkyl-palladium N-heterocyclic carbene complexes. AB - The transamination of alkyl-palladium halide N-heterocyclic carbene complexes has enabled the isolation of products that reveal interesting insights into the factors which might be barriers to the development of a palladium-catalysed alkyl amination reaction. PMID- 17347725 TI - Use of porous anodic alumina membranes as a nanometre-diameter column for high performance liquid chromatography. AB - The possibility of using porous anodic alumina membranes as a column for normal phase high performance liquid chromatography was evaluated using phenol and toluene with mobile phases having different solvent compositions. PMID- 17347726 TI - Synthesis of molecular imprinted polymer coated photocatalysts with high selectivity. AB - Molecular imprinted polymer coated photocatalysts were prepared via polymerization of a proper functional monomer in the presence of TiO(2) nanoparticles and target molecules, which was found to promote the selectivity of TiO(2) photocatalysis. PMID- 17347727 TI - A new chiral diiron catalyst for enantioselective epoxidation. AB - The dinuclear chiral complex Fe(2)O(bisPB)(4)(X)(2)(ClO(4))(4) (X = H(2)O or CH(3)CN) catalyzes with high efficiency (up to 850 TON) and moderate enantioselectivity (63%) the epoxidation of electron deficient alkenes at 0 degrees C by a peracid. PMID- 17347728 TI - A photoswitchable molecular wire with the dithienylethene (DTE) linker, (dppe)(eta(5)-C(5)Me(5))Fe-C[triple bond, length as m-dash]C-DTE-C[triple bond, length as m-dash]C-Fe(eta(5)-C(5)Me(5))(dppe). AB - A redox-active diiron complex with the diethynylated dithienylethene (DTE) linker, (dppe)(eta(5)-C(5)Me(5))Fe-C[triple bond, length as m-dash]C-DTE-C[triple bond, length as m-dash]C-Fe(eta(5)-C(5)Me(5))(dppe), shows photochromic behaviour, which switches on and off the communication performance between the two metal centres. PMID- 17347729 TI - Pore-expansion of monodisperse mesoporous silica spheres by a novel surfactant exchange method. AB - By adapting a novel surfactant exchange method, in which surfactants inside mesopores are completely exchanged by surfactants with longer alkyl chain lengths, pore-expansion of monodisperse mesoporous silica spheres (MMSS) with radially ordered hexagonal regularity was attained while retaining spherical morphology and high monodispersity. PMID- 17347730 TI - Enantio- and diastereo-controlled synthesis of (+)-juvabione employing organocatalytic desymmetrization and photoinduced fragmentation. AB - (+)-Juvabione, a natural sesquiterpene exhibiting insect juvenile hormone activity, has been synthesized from sigma-symmetric 4-(2-formyl ethyl)cyclohexanone by employing organocatalytic asymmetric aldolization and Norrish I-type fragmentation as the key steps. PMID- 17347731 TI - Formation of nanostructured, nanocrystalline boron nitride microparticles with diatom-derived 3-D shapes. AB - The first use of diatom frustules as shape-dictating 3-D templates for the syntheses of nanostructured, nanocrystalline micro-particles of a non-oxide ceramic, boron nitride, is demonstrated. PMID- 17347732 TI - Isoquinolin-1-ylidenes as electronically tuneable ligands. AB - The novel isoquinolin-1-ylidene ligands, introduced into Rh(I) complexes by exploiting the carbene-like reactivity of adducts , exhibit ligand properties similar to those of classic NHCs, and their electronic properties can be tuned by the introduction of electron-withdrawing or donating groups in the benzene ring. PMID- 17347733 TI - Only para-hydrogen spectroscopy (OPSY), a technique for the selective observation of para-hydrogen enhanced NMR signals. AB - An NMR method is reported for the efficient removal of signals derived from nuclei with thermally equilibrated spin state populations whilst leaving, intact, signals derived from para-hydrogen induced polarisation (PHIP) through gradient assisted coherence selection. PMID- 17347735 TI - Proceedings of the 5th International Workshop on Biosignal Interpretation, September 6-8, 2005, Tokyo, Japan. PMID- 17347736 TI - Online Bayesian modeling and prediction of nonlinear systems--Sequential Monte Carlo approach. AB - OBJECTIVES: Given time-series data from an unknown target system, one often wants to build a model for the system behind the data and make predictions. If the target system can be assumed to be linear, there are means of modeling and predicting the target system in question. If, however, one cannot assume the system is linear, various linear theories have natural limitations in terms of modeling and predictive capabilities. This paper attempts to construct a model from time-series data and make an online prediction when the linear assumption is not valid. METHODS: The problem is formulated within a Bayesian framework implemented by the Sequential Monte Carlo method. Online Bayesian learning/prediction requires computation of a posterior distribution in a sequential manner as each datum arrives. The Sequential Monte Carlo method computes the importance weight in order to draw samples from the posterior distribution. The scheme is tested against time-series data from a noisy Rossler system. RESULTS: The test time-series data is the x-coordinate of the trajectory generated by a noisy Roessler system. Attempts are made with regard to online reconstruction of the attractor and online prediction of the time-series data. CONCLUSIONS: The proposed algorithm appears to be functional. The algorithm should be tested against real world data. PMID- 17347737 TI - An approach to estimate time-varying casual coherence function. AB - OBJECTIVES: This paper describes the development of a model-based approach to estimating both open-loop and causal time-varying coherence functions (TVCF). Theoretical derivations of the coherence bounds using the proposed approach are also provided. METHODS: A time-varying vector autoregressive (VAR) model was used to estimate both open-loop and causal TVCF. The time-varying optimal parameter search method was employed to identify the time-varying model coefficients as well as the model order of the VAR model. RESULTS: Simulation results revealed interesting observations, and they were corroborated using experimental renal blood pressure and flow data. Specifically, experimental data showed that in certain cases, the calculation of the open-loop TVCF might provide incorrect interpretation of the results when the system under investigation was a closed loop system, which is consistent with theoretical derivations. CONCLUSIONS: The use of the closed-loop TVCF not only provides quantitative assessment of the coupling between the two signals, but it also provides valuable insights into the composition of the physical structure of the system. PMID- 17347738 TI - Information theoretic equivalent bandwidths of random processes and their applications. AB - OBJECTIVES: Since most of the biomedical signals, such as electroencephalogram (EEG), electromyogram (EMG) and phonocardiogram (PCG), are nonstationary random processes, the time-frequency analysis has recently been extensively applied to those signals in order to achieve precise characterization and classification. In this paper, we have first defined a new class of information theoretic equivalent bandwidths (EBWs) of stationary random processes, then instantaneous EBWs (IEBWs) using nonnegative time-frequency distributions have been defined in order to track the change of the EBW of a nonstationary random process. METHODS: The new class of EBWs which includes spectral flatness measure (SFM) for stationary random processes is defined by using generalized Burg entropy. Generalized Burg entropy is derived from the relation between Renyi entropy and Renyi information divergence of order alpha. In order to track the change of EBWs of a nonstationary random process, the IEBWs are defined on the nonnegative time frequency distributions, which are constructed by the Copula theory. RESULTS: We evaluate the IEBWs for a first order stationary auto-regressive (AR) process and three types of time-varying AR processes. The results show that the IEBWs proposed here properly represent a signal bandwidth. In practical application to PCGs, the proposed method was successful in extracting the information that the bandwidth of the innocent systolic murmur was much smaller than that of the abnormal systolic murmur. CONCLUSIONS: We have defined new information theoretic EBWs and have proposed a novel method to track the change of the IEBWs. Some computer simulation showed effectiveness of the methods. Applying the IEBWs to PCGs, we could extract some features of a systolic murmur. PMID- 17347739 TI - Wavelet-based estimation of generalized fractional process. AB - OBJECTIVES: This paper aims to propose an estimation procedure for the parameters of a generalized fractional process, a fairly general model of long-memory applicable in modeling biomedical signals whose autocorrelations exhibit hyperbolic decay. METHODS: We derive a wavelet-based weighted least squares estimator of the long-memory parameter based on the maximal-overlap estimator of the wavelet variance. Short-memory parameters can then be estimated using standard methods. We illustrate our approach by an example applying ECG heart rate data. RESULTS AND CONCLUSION: The proposed method is relatively computationally and statistically efficient. It allows for estimation of the long memory parameter without knowledge of the short-memory parameters. Moreover it provides a more general model of biomedical signals that exhibit periodic long range dependence, such as ECG data, whose relatively unobtrusive recording may be advantageous in assessing or predicting some physiological or pathological conditions from the estimated values of the parameters. PMID- 17347740 TI - Information flow enables specific identification of particular physiological controllers based on their time scales. AB - OBJECTIVES: Complex physiological systems, such as the cardiovascular system, controlled by the autonomic nervous system, and the gait and posture system, controlled by the sensomotor nervous system, incorporate several controllers acting at different time scales. We investigated the question, whether the information flow as a function of prediction time enables the identification of those contributing controllers within the entire complex system behavior. METHODS: Information flow functions assess the predictability of a time series. They were calculated based on mutual information over prediction time horizon tau. The importance of considering appropriate time scales tau was introduced by a simulation study of an excited pendulum. Based on heart rate data, complex autonomic dysfunctions were assessed by using autonomic information flow (AIF) in an experimental study of rats and in clinical studies of patients with multiple organ dysfunction syndrome (MODS) and after cardiac arrest (CA). Motor dysfunction in elderly suffering from low back pain was assessed by gait information flow (GIF) based on back movements. RESULTS: In rats, AIF over one heart beat period was reduced due to anesthesia, AIF over vagal time scale was increased due to vagotomy. In both, MODS and CA patients, vagal time scale AIF was reduced, but longterm AIF was increased. In low back pain patients, short loop GIF was increased, but walking period-related GIF was reduced. CONCLUSIONS: Information flow functions allow the identification of particular controllers and their interdependencies within complex physiological systems. PMID- 17347741 TI - Application of the Ramanujan Fourier Transform for the analysis of secondary structure content in amino acid sequences. AB - OBJECTIVE: A novel method is presented for the investigation of protein properties of sequences using Ramanujan Fourier Transform (RFT). METHODS: The new methodology involves the preprocessing of protein sequence data by numerically encoding it and then applying the RFT. The RFT is based on projecting the obtained numerical series on a set of basis functions constituted by Ramanujan sums (RS). In RS components, periodicities of finite integer length, rather than frequency, (as in classical harmonic analysis) are considered. RESULTS: The potential of the new approach is documented by a few examples in the analysis of hydrophobic profiles of proteins in two classes including abundance of alpha helices (group A) or beta-strands (group B). Different patterns are provided as evidence. CONCLUSIONS: RFT can be used to characterize the structural properties of proteins and integrate complementary information provided by other signal processing transforms. PMID- 17347742 TI - "Mobile Nurse" platform for ubiquitous medicine. AB - OBJECTIVES: We introduce "Mobile Nurse" (MN) - an emerging platform for the practice of ubiquitous medicine. METHODS: By implementing in a dynamic setting of daily life the patient care traditionally provided by the clinical nurses on duty, MN aims at integral data collection and shortening the response time to the patient. MN is also capable of intelligent interaction with the patient and is able to learn from the patient's behavior and disease sign evaluation for improved personalized treatment. RESULTS: In this paper, we outline the most essential concepts around the hardware, software and methodological designs of MN. We provide an example of the implementation, and elaborate on the possible future impact on medical practice and biomedical science research. CONCLUSIONS: The main innovation of MN, setting it apart from current tele-medicine systems, is the ability to integrate the patient's signs and symptoms on site, providing medical professionals with powerful tools to elucidate disease mechanisms, to make proper diagnoses and to prescribe treatment. PMID- 17347743 TI - Wavelet-based segmentation and feature extraction of heart sounds for intelligent PDA-based phonocardiography. AB - OBJECTIVES: Many pathological conditions of the cardiovascular system cause murmurs and aberrations in heart sounds. Phonocardiography provides the clinician with a complementary tool to record the heart sounds heard during auscultation. The advancement of intracardiac phonocardiography combined with modern digital signal processing techniques has strongly renewed researchers' interest in studying heart sounds and murmurs. The aim of this work is to investigate the applicability of different spectral analysis methods to heart sound signals and explore their suitability for PDA-based implementation. METHODS: Fourier transform (FT), short-time Fourier transform (STFT) and wavelet transform (WT) are used to perform spectral analysis on heart sounds. A segmentation algorithm based on Shannon energy is used to differentiate between first and second heart sounds. Then wavelet transform is deployed again to extract 64 features of heart sounds. RESULTS: The FT provides valuable frequency information but the timing information is lost during the transformation process. The STFT or spectrogram provides valuable time-frequency information but there is a trade-off between time and frequency resolution. Wavelet analysis, however, does not suffer from limitations of the STFT and provides adequate time and frequency resolution to accurately characterize the normal and pathological heart sounds. CONCLUSIONS: The results show that the wavelet-based segmentation algorithm is quite effective in localizing the important components of both normal and abnormal heart sounds. They also demonstrate that wavelet-based feature extraction provides suitable feature vectors which are clearly differentiable and useful for automatic classification of heart sounds. PMID- 17347744 TI - Neural engineering--a new discipline for analyzing and interacting with the nervous system. AB - OBJECTIVES: The field of neural engineering focuses on an area of research at the interface between neuroscience and engineering. The area of neural engineering was first associated with the brain machine interface but is much broader and encompasses experimental, computational, and theoretical aspects of neural interfacing, neuroelectronics, neuromechanical systems, neuroinformatics, neuroimaging, neural prostheses, artificial and biological neural circuits, neural control, neural tissue regeneration, neural signal processing, neural modelling and neuro-computation. One of the goals of neural engineering is to develop a selective interface for the peripheral nervous system. METHODS: Nerve cuffs electrodes have been developed to either reshape or maintain the nerve into an elongated shape in order to increase the circumference to cross sectional ratio. It is then possible to place many electrodes around the nerve to achieve selectivity. This new cuff (flat interface nerve electrode: FINE) was applied to the hypoglossal nerve and the sciatic nerve in dogs and cats to estimate the selectivity of the interface. RESULTS: By placing many contacts close to the axons, three different types of selectivity were achieved: 1) The FINE could generate a high degree of stimulation selectivity as estimated by the individual fascicle recording. 2) Similarly, recording selectivity was also demonstrated and blind source algorithms were applied to recover the signals. 3) Finally, by placing arrays of electrodes along the nerve, small fiber diameters could be excited before large fibers thereby reversing the recruitment order. CONCLUSION: Taking advantage of the fact that nerves are not round but oblong or flat allows a novel design for selective nerve interface with the peripheral nervous system. This new design has found applications in many disorders of the nervous system such as bladder incontinence, obstructive sleep apnea and stroke. PMID- 17347745 TI - Efficient signal processing of multineuronal activities for neural interface and prosthesis. AB - OBJECTIVES: Multineuronal spike trains must be efficiently decoded in order to utilize them for controlling artificial limbs and organs. Here we evaluated the efficiency of pooling (averaging) and combining (vectorizing) activities of multiple neurons for decoding neuronal information. METHODS: Multineuronal activities in the monkey inferior temporal (IT) cortex were obtained by classifying spikes of constituent neurons from multichannel data recorded with a multisite microelectrode. We compared pooling and combining procedures for the amount of visual information transferred by neurons, and for the success rate of stimulus estimation based on neuronal activities in each trial. RESULTS: Both pooling and combining activities of multiple neurons increased the amount of information and the success rate with the number of neurons. However, the degree of improvement obtained by increasing the number of neurons was higher when combining activities as opposed to pooling them. CONCLUSION: Combining the activities of multiple neurons is more efficient than pooling them for obtaining a precise interpretation of neuronal signals. PMID- 17347746 TI - Estimation of parameters in Shot-Noise-Driven Doubly Stochastic Poisson processes using the EM algorithm--modeling of pre- and postsynaptic spike trains. AB - OBJECTIVES: To estimate the parameters, the impulse response (IR) functions of some linear time-invariant systems generating intensity processes, in Shot-Noise Driven Doubly Stochastic Poisson Process (SND-DSPP) in which multivariate presynaptic spike trains and postsynaptic spike trains can be assumed to be modeled by the SND-DSPPs. METHODS: An explicit formula for estimating the IR functions from observations of multivariate input processes of the linear systems and the corresponding counting process (output process) is derived utilizing the expectation maximization (EM) algorithm. RESULTS: The validity of the estimation formula was verified through Monte Carlo simulations in which two presynaptic spike trains and one postsynaptic spike train were assumed to be observable. The IR functions estimated on the basis of the proposed identification method were close to the true IR functions. CONCLUSIONS: The proposed method will play an important role in identifying the input-output relationship of pre- and postsynaptic neural spike trains in practical situations. PMID- 17347747 TI - Enhancement of classification accuracy of a time-frequency approach for an EEG based brain-computer interface. AB - OBJECTIVES: The aim of this paper is to develop a new algorithm to enhance the performance of EEG-based brain-computer interface (BCI). METHODS: We improved our time-frequency approach of classification of motor imagery (MI) tasks for BCI applications. The approach consists of Laplacian filtering, band-pass filtering and classification by correlation of time-frequency-spatial patterns. RESULTS AND CONCLUSIONS: Through off-line analysis of data collected during a "cursor control" experiment, we evaluated the capability of our new method to reveal major features of the EEG control for enhancement of MI classification accuracy. The pilot results in a human subject are promising, with an accuracy rate of 96.1%. PMID- 17347748 TI - Fast feature selection to compare broadband with narrowband phase synchronization in brain-computer interfaces. AB - OBJECTIVE: Brain-computer interface (BCI) research aims at developing communication devices for the motor disabled. Such devices are not driven by muscle activity, but by brain activity recorded during different mental tasks. We present here the comparison of phase synchronization and power spectral density (PSD) features, computed from broadband and narrowband filtered EEG signals and their ability to discriminate three mental tasks. METHODS: EEG signals were recorded from five subjects while performing left and right hand movement imagination and word generation. We applied a modified Fast Correlation Based Filter (FCBF) [9] for the purpose of feature selection. RESULTS: We found that the features were selected from electrode signals corresponding to neurophysiological evidence, i.e. electrodes lying over the motor cortex. PSD and phase locking value (PLV) features were more discriminative when computed from narrowband (8-12 Hz) and broadband (8-30 Hz) filtered signals respectively. CONCLUSIONS: The generalization performance is as good as the one obtained with SVM-rfe, but this algorithm is faster and selects fewer features. These properties may make FCBF a valuable tool for further improvement of BCIs. PMID- 17347749 TI - Cross-correlation analysis of the correspondence between magnetoencephalographic and near-infrared cortical signals. AB - OBJECTIVES: The study of neurovascular coupling greatly benefits from combined measurements of neuronal and vascular signals. Two-step signal processing is developed to extract parameters describing the coupling. METHODS: Using a magnetometer in an extremely well shielded room a broadband magnetoencephalogram was simultaneously measured with time-resolved near-infrared spectroscopy during a motor activity paradigm. The raw MEG and NIRS data were denoised separately using independent component analysis. RESULTS: After averaging the resulting signals showed motor activity-related changes. The temporal correspondence between MEG and NIRS was assessed plotting a combined trajectory and calculating a cross-correlation. Compared to the MEG signal, at movement onset the NIRS signal showed an onset delay in the range of seconds. CONCLUSIONS: Multi-variate signal pre-processing followed by temporal delay estimates demonstrated the extraction of neurovascular coupling parameters. PMID- 17347750 TI - relationship between the binary kernels of visually evoked potentials and the visual responses on the magnocellular and parvocellular pathways. AB - OBJECTIVES: To investigate the nonlinear characteristics of visual evoked potentials (VEPs), and their correlation with the visual responses on parvocellular and magnocellular pathways. First and second-order kernels of the VEPs elicited by several checkerboard patterns were estimated, and their relations to the visual pathway responses were investigated. METHODS: VEPs elicited by checkerboard pattern (0.5, 1.0, 2.0 and 4.0 c/d) alternating based on pseudorandom binary sequence were measured, and their binary kernels were calculated. First and second-order binary kernels were compared with amplitudes of the steady-state VEPs (S-VEPs) to pattern reversal stimulation with a constant temporal frequency (4, 8, 12, 16, and 32 Hz). RESULTS: Positive peak latencies at 150 ms (P150) of second-order first and second slices were correlated with S-VEP amplitude for higher temporal frequencies, indicating that the first and second slices reflect the response of the magnocellular. However, for second and third slices, their amplitudes were partially correlated with 4-16 Hz S-VEP, and this indicated that the second slice contains both magno- and parvocellular pathway responses. P150 latencies of third slices were correlated with S-VEP for lower temporal frequencies, indicating that third slice reflects the response of the parvocellular pathway. CONCLUSIONS: The lower slices of second-order binary kernels reflect the response of the magnocellular pathway and the higher slices reflect those on the parvocellular pathway in the human visual system of VEPs. PMID- 17347751 TI - Autonomic imbalance induced breakdown of long-range dependence in healthy heart rate. AB - OBJECTIVES: The investigation of the relation between the long-range correlation property of heart rate and autonomic balance. METHODS: An investigation of the fractal scaling properties of heart rate variability was carried out by using detrended fluctuation analysis (DFA). Eleven healthy subjects were examined for two consecutive days, which included usual daily activity, strenuous prolonged experimental exercise, and sleep. We also considered two patient groups with autonomic dysfunction characterized by selective sympathetic and parasympathetic dominance. RESULTS: Robust long-range dependence in heart rate is observed only in the state of usual daily activity, characterized by normal heart rate typical of balanced autonomic sympathetic and parasympathetic regulation. This confirms the previously postulated behavioral independence of heart rate regulation, but reveals that the occurrence of 1/f, long-range dependence is restricted to only the state of autonomic balance. Both the sympathetic dominant high heart rate state, realized during strenuous experimental exercise, and the parasympathetic dominant low heart rate state, prevalent in (deep) sleep, are characterized by uncorrelated, near white-noise-like scaling, lacking long-range dependence. CONCLUSION: Remarkably, the breakdown of the long-range correlations observed in healthy heart rate in the states of sympathetic and parasympathetic dominance is in stark contrast to the increased correlations which have previously been observed in neurogenic parasympathetic and sympathetic dominance in patients suffering from primary autonomic failure and congestive heart failure, respectively. Our findings further reveal the diagnostic capabilities of heart rate dynamics, by differentiating physiological healthy states from pathology. PMID- 17347752 TI - Investigation of the influence of swallowing, coughing and vocalization on heart rate variability with respiratory-phase domain analysis. AB - OBJECTIVES: The objective of our study is to investigate extrinsic influences on heart rate variability using respiratory-phase domain analysis. Swallowing, coughing and vocalization (reading aloud and conversation) are adopted as extrinsic influences. METHODS: In this study, an instantaneous R-R interval (RRI) is sampled at each pi/10 rad of the respiratory phase and the data is divided into three subsets: a) respiration with event, b) one respiration after the event, and c) normal respiration. Then the mean waveforms of respiratory sinus arrhythmia (RSA) are calculated and compared. RESULTS AND CONCLUSIONS: It is found that swallowing induces tachycardia that recovers within one respiration. Coughing also induces tachycardia, but it does not recover within one respiration. Vocalization shortens the mean RRI, but the changing respiratory pattern due to vocalization has no statistically significant influence on the amplitude of RSA. Furthermore, it is found that the proposed method is effective for analyzing extrinsic influences on heart rate variability (HRV). PMID- 17347753 TI - Comparison between fetal heart rate standard parameters and complexity indexes for the identification of severe intrauterine growth restriction. AB - OBJECTIVES: The intrauterine growth restriction (IUGR) is a pathological state: the fetus is at risk of hypoxia and this condition is associated with increased perinatal morbidity and mortality. However, evidence-based guidelines for clinical surveillance are poor and lack reliable indexes. This study introduces new procedures to extract parameters from the fetal heart rate signal in order to identify severe intrauterine growth restricted (IUGR) fetuses METHODS: Standard parameters (time domain and frequency domain indexes) are compared to a new parameter, the Lempel Ziv complexity, and to two regularity estimators (approximate entropy and sample entropy). The paper analyzes the robustness of the indexes coming from the parameter extraction procedure. RESULTS AND CONCLUSIONS: The results show that the LZ complexity is a stable parameter and it is able to significantly discriminate the severe IUGR (preterm delivered) from moderate IUGR (at term delivered) and from healthy fetuses. PMID- 17347754 TI - Analysis of heart rate variability to predict patient age in a healthy population. AB - OBJECTIVES: To estimate age of healthy subjects by means of the heart rate variability (HRV) parameters thus assessing the potentiality of HRV indexes as a biomarker of age. METHODS: Long-term indexes of HRV in time domain, frequency domain and non-linear parameters were computed on 24-hour recordings in a dataset of 63 healthy subjects (age range 20-76 years old). Then, as interbeat dynamics markedly change with age, showing a reduced HRV in older subjects, we tried to capture age-related influence on HRV by principal component analysis and to predict the subject age by means of a feedforward neural network. RESULTS: The network provides good prediction of patient age, even if a slight overestimation in the younger subjects and a slight underestimation in the older ones were observed. In addition, the important contribution of non-linear indexes to prediction is underlined. CONCLUSIONS: HRV as a predictor of age may lead to the definition of a new biomarker of aging. PMID- 17347755 TI - Fetal heart rate deceleration detection using a discrete cosine transform implementation of singular spectrum analysis. AB - OBJECTIVES: To develop a singular-spectrum analysis (SSA) based change-point detection algorithm applicable to fetal heart rate (FHR) monitoring to improve the detection of deceleration events. METHODS: We present a method for decomposing a signal into near-orthogonal components via the discrete cosine transform (DCT) and apply this in a novel online manner to change-point detection based on SSA. The SSA technique forms models of the underlying signal that can be compared over time; models that are sufficiently different indicate signal change points. To adapt the algorithm to deceleration detection where many successive similar change events can occur, we modify the standard SSA algorithm to hold the reference model constant under such conditions, an approach that we term "base hold SSA". The algorithm is applied to a database of 15 FHR tracings that have been preprocessed to locate candidate decelerations and is compared to the markings of an expert obstetrician. RESULTS: Of the 528 true and 1285 false decelerations presented to the algorithm, the base-hold approach improved on standard SSA, reducing the number of missed decelerations from 64 to 49 (21.9%) while maintaining the same reduction in false-positives (278). CONCLUSIONS: The standard SSA assumption that changes are infrequent does not apply to FHR analysis where decelerations can occur successively and in close proximity; our base-hold SSA modification improves detection of these types of event series. PMID- 17347756 TI - Effect of common driving sources to the feedback analysis of heart rate variability. AB - OBJECTIVES: This paper examines the operational characteristics of the multivariate autoregressive analysis applied to the simultaneous recordings of the instantaneous heart rate (IHR) and the change in systolic blood pressure (SBP). METHODS: The multivariate autoregressive model has been utilized to reveal the feedback characteristics between IHR and SBP. The model assumes the presence of independent set of driving forces to activate the system. However, it is likely that the driving forces may have correlation due to the presence of a common fluctuation source. This paper examines the effect of the presence of correlated components in the driving forces to the estimation accuracy of impulse responses characterizing the feedback properties. The two-dimensional autoregressive model driven by two correlated 1/f noises was chosen for the analysis of operational characteristics. The driving force was generated by a moving average system which simulates non-integer order integration. RESULTS: Computer simulation revealed that the mean square estimation errors of impulse responses sharply increase as relative power of common driving force exceeds 50%. However, the estimation accuracy and bias are found to be in permissible range in practice. CONCLUSIONS: These findings ensure the practical validity of utilizing multivariate autoregressive models for the feedback analysis between IHR and SBP where both signals have the common driving force. PMID- 17347757 TI - New methods for time-resolved fluorescence spectroscopy data analysis based on the Laguerre expansion technique--applications in tissue diagnosis. AB - OBJECTIVES: A new deconvolution method for the analysis of time-resolved laser induced fluorescence spectroscopy (TR-LIFS) data is introduced and applied for tissue diagnosis. METHOD: The intrinsic TR-LIFS decays are expanded on a Laguerre basis, and the computed Laguerre expansion coefficients (LEC) are used to characterize the sample fluorescence emission. The method was applied for the diagnosis of atherosclerotic vulnerable plaques. RESULTS: At a first stage, using a rabbit atherosclerotic model, 73 TR-LIFS in-vivo measurements from the normal and atherosclerotic aorta segments of eight rabbits were taken. The Laguerre deconvolution technique was able to accurately deconvolve the TR-LIFS measurements. More interesting, the LEC reflected the changes in the arterial biochemical composition and provided discrimination of lesions rich in macrophages/foam-cells with high sensitivity (> 85%) and specificity (> 95%). At a second stage, 348 TR-LIFS measurements were obtained from the explanted carotid arteries of 30 patients. Lesions with significant inflammatory cells (macrophages/foam-cells and lymphocytes) were detected with high sensitivity (> 80%) and specificity (> 90%), using LEC-based classifiers. CONCLUSION: This study has demonstrated the potential of using TR-LIFS information by means of LEC for in vivo tissue diagnosis, and specifically for detecting inflammation in atherosclerotic lesions, a key marker of plaque vulnerability. PMID- 17347758 TI - Independent component analysis and neural networks applied for classification of malignant, benign and normal tissue in digital mammography. AB - OBJECTIVES: This paper proposes an efficient method for the discrimination and classification of mammograms with benign, malignant and normal tissues. METHODS: The proposed method consists of selection of tissues, feature extraction using independent component analysis, feature selection by the forward-selection technique and classification of the tissue by the multilayer perceptron. RESULTS: The method is tested for a mammogram set of the MIAS database, resulting in a 97.83% success rate, with 98.0% specificity and 97.5% sensitivity. CONCLUSION: The proposed method showed a good classification rate. The method will be useful for early cancer diagnosis. PMID- 17347759 TI - Detection of sleep apnea episodes from multi-lead ECGs considering different physiological influences. AB - OBJECTIVES: This article deals with recognition of sleep apnea, using solely information available from multi-lead ECGs. METHODS: Characteristic variations in heart rhythm and amplitude of the ECG are compared with respect to their diagnostic accuracy by means of an ROC analysis that is performed on a local similarity index. In 38 8-lead ECGs, each minute is classified with respect to occurrence of apnea events and the result is validated against expert annotations derived from synchronized polysomnographic recordings. Moreover, the results are compared to those obtained from the well known Physionet apnea-ECG database. RESULTS: Whereas the effect of amplitude modulation yields consistent results on both data sets (ROC-area 89.0% vs. 88.3%), a remarkable loss in performance is observed for the frequently applied heart rhythm (89.8% vs. 77.9%). Examples illustrating the reasons for this difference are given and discussed. With respect to aggregation of multi-lead information, two methods (PCA vs. averaging) are compared. The results indicate that averaging performs better (89.3%) than the adaptively estimated PCA (87.2) even when applied to a reduced set of leads. CONCLUSIONS: It is concluded that sleep apnea recognition from heart rhythm should always be complemented by analysis of the amplitude variations of the ECG. PMID- 17347760 TI - Long-range correlated glucose fluctuations in diabetes. AB - OBJECTIVES: Our objective is to investigate diabetes-related alteration of glucose control in diurnal fluctuations in normal daily life by detrended fluctuation analysis (DFA). METHODS: The fluctuations of glucose of 12 non diabetic subjects and 15 diabetic patients were measured using a continuous glucose monitoring system (CGMS) over a period of one day. The glucose data was calculated by the DFA method, which is capable of revealing the presence of long range correlations in time series with inherent non-stationarity. RESULTS: Compared with the non-diabetic subjects, the mean glucose level and the standard deviation are significantly higher in the diabetic group. The DFA exponent alpha is calculated, and glucose time series are searched for the presence of negatively (0.5 < alpha < 1.5) or positively (1.5 < alpha) correlated fluctuations. A crossover phenomenon, i.e. a change in the level of correlations, is observed in the non-diabetic subjects at about two hours; the net effects of glucose flux/reflux causing temporal changes in glucose concentration are negatively correlated in a "long-range" (> two hours) regime. However, for diabetic patients, the DFA exponent alpha = 1.65 +/- 0.30, and in the same regime positively correlated fluctuations are observed, suggesting that the net effects of the flux and reflux persist for many hours. CONCLUSIONS: Such long-range positive correlation in glucose homeostasis may reflect pathogenic mechanisms of diabetes, i.e., the lack of the tight control in blood glucose regulation. Using modern time series analysis methods such as DFA, continuous evaluation of glucose dynamics could promote better diagnoses and prognoses of diabetes and a better understanding of the fundamental mechanism of glucose dysregulation in diabetes. PMID- 17347761 TI - Improved ECG signal analysis using wavelet and feature extraction. AB - OBJECTIVES: Automatic detection of arrhythmias is important for diagnosis of heart problems. However, in ECG signals, there is significant variation of waveforms in both normal and abnormal beats. It is this phenomenon, which makes it difficult to analyse ECG signals. The aim of developing methodology is to distinguish between normal beats and abnormal beats in an ECG signal. METHODS: ECG signals were first decomposed using wavelet transform. The feature vectors were then extracted from these decomposed signals as normalised energy and entropy. To improve the classification of the feature vectors of normal and abnormal beats, the normal beats which occur before and after the abnormal beats were eliminated from the group of normal beats. RESULTS: With our proposed methods, the normal beats and abnormal beats formed different clusters of vector points. By eliminating normal beats which occur before and after the abnormal beats, the clusters of different types of beats showed more apparent separation. CONCLUSIONS: The combination of wavelet decomposition and the classification using feature vectors of the beats in ECG signals separate abnormal beats from normal beats. The elimination of the normal beats which occur before and after the abnormal beats succeeded in minimising the size of normal beats cluster. PMID- 17347762 TI - Using deconvolution to improve PET spatial resolution in OSEM iterative reconstruction. AB - OBJECTIVES: A novel approach to the PET image reconstruction is presented, based on the inclusion of image deconvolution during conventional OSEM reconstruction. Deconvolution is here used to provide a recovered PET image to be included as "a priori" information to guide OSEM toward an improved solution. METHODS: Deconvolution was implemented using the Lucy-Richardson (LR) algorithm: Two different deconvolution schemes were tested, modifying the conventional OSEM iterative formulation: 1) We built a regularizing penalty function on the recovered PET image obtained by deconvolution and included it in the OSEM iteration. 2) After each conventional global OSEM iteration, we deconvolved the resulting PET image and used this "recovered" version as the initialization image for the next OSEM iteration. Tests were performed on both simulated and acquired data. RESULTS: Compared to the conventional OSEM, both these strategies, applied to simulated and acquired data, showed an improvement in image spatial resolution with better behavior in the second case. In this way, small lesions, present on data, could be better discriminated in terms of contrast. CONCLUSIONS: Application of this approach to both simulated and acquired data suggests its efficacy in obtaining PET images of enhanced quality. PMID- 17347763 TI - Using block-based multiparameter representation to detect tumor features on T2 weighted brain MRI images. AB - OBJECTIVE: The objective of this paper is to present an analytical method for digitized images to detect tumors or lesions in a medical decision support system. METHOD: The authors have developed a simple method of tumor detection using three parameter values: edge (E), gray (G), and contrast (H). The method proposed here first studied the VHD (Visible Human Dataset) input brain feature using EGH parameters that divided the input image into fixed-size blocks (templates). The EGH parameters for the feature blocks were calculated and parameterized to detect the occurrences of abnormalities. These abnormal blocks were then marked for interpretation. RESULTS: Measurements of the following medical dataset were performed: 1) different time-interval images from the same dataset, 2) different brain disease images from multiple datasets, and 3) multiple slice images from multiple datasets. Our experimental results illustrate the ability of our proposed technique to detect tumor blocks with conceptual simplicity and computational efficiency. CONCLUSION: In this paper, we present output examples from our prototype system, comparing detection accuracy and system performance. PMID- 17347764 TI - Cortical dipole imaging of movement-related potentials by means of parametric inverse filters incorporating with signal and noise covariance. AB - OBJECTIVE: The objective of this study is to explore suitable spatial filters for inverse estimation of cortical equivalent dipole layer imaging from the scalp electroencephalogram. We utilize cortical dipole source imaging to locate the possible generators of scalp-measured movement-related potentials (MRPs) in human. METHODS: The effects of incorporating signal and noise covariance into inverse procedures were examined by computer simulations and experimental study. The parametric projection filter (PPF) and parametric Weiner filter (PWF) were applied to an inhomogeneous three-sphere head model under various noise conditions. RESULTS: The present simulation results suggest that the PWF incorporating signal information provides better cortical dipole layer imaging results than the PPF and Tikhonov regularization under the condition of moderate and high correlation between signal and noise distributions. On the other hand, the PPF has better performance than other inverse filters under the condition of low correlation between signal and noise distributions. The proposed methods were applied to self-paced MRPs in order to identify the anatomic substrate locations of neural generators. The dipole layer distributions estimated by means of PPF are well-localized as compared with blurred scalp potential maps and dipole layer distribution estimated by Tikhonov regularization. The proposed methods demonstrated that the contralateral premotor cortex was preponderantly activated in relation to movement performance. CONCLUSIONS: In cortical dipole source imaging, the PWF has better performance especially when the correlation between the signal and noise is high. The proposed inverse method was applicable to human experiments of MRPs if the signal and noise covariances were obtained. PMID- 17347765 TI - Neural responses to human voice and hemisphere dominance for lexical-semantic processing--an fMRI study. AB - OBJECTIVES: In our previous functional magnetic resonance imaging (fMRI) study, we determined that there was distinct left hemispheric dominance for lexical semantic processing without the influence of human voice perception in right handed healthy subjects. However, the degree of right-handedness in the right handed subjects ranged from 52 to 100 according to the Edinburgh Handedness Inventory (EHI) score. In the present study, we aimed to clarify the correlation between the degree of right-handedness and language dominance in the fronto temporo-parietal cortices by examining cerebral activation for lexical-semantic processing. METHODS: Twenty-seven normal right-handed healthy subjects were scanned by fMRI while listening to sentences (SEN), reverse sentences (rSEN), and identifiable non-vocal sounds (SND). Fronto-temporo-parietal activation was observed in the left hemisphere under the SEN - rSEN contrast, which included lexical-semantic processing without the influence of human voice perception. Laterality Index was calculated as LI = (L - R)/(L + R) x 100, L: left, R: right. RESULTS: Laterality Index in the fronto-temporo-parietal cortices did not correlate with the degree of right-handedness in EHI score. CONCLUSIONS: The present study indicated that the degree of right-handedness from 52 to 100 in EHI score had no effect on the degree of left hemispheric dominance for lexical semantic processing in right-handed healthy subjects. PMID- 17347766 TI - Consistent treatment of length variants in the human mtDNA control region: a reappraisal. AB - In forensic science, as well as in molecular anthropology and medical genetics, human mitochondrial DNA (mtDNA) variation is being recorded by aligning mtDNA sequences to the revised Cambridge reference sequence (rCRS). This task is straightforward for the vast majority of nucleotide positions but appears to be difficult for some short sequence stretches, namely, in regions displaying length variation. Earlier guidelines for imposing a unique alignment relied on binary alignment to a standard sequence (the rCRS) and used additional priority rules for resolving ambiguities. It turns out, however, that these rules have not been applied rigorously and led to inconsistent nomenclature. There is no way to adapt the priority rules in a reasonable way because binary alignment to a standard sequence is bound to produce artificial alignments that may place sequences separated by a single mutation at mismatch distance larger than 1. To remedy the situation, we propose a phylogenetic approach for multiple alignment and resulting notation. PMID- 17347767 TI - An intraorbital wooden foreign body: description of a case and a variety of CT appearances. AB - We present a case report in which a 4-year-old girl was involved in a fall that resulted in an injury of the right orbita. The girl kept a chopstick in her right hand that got into the right orbita due to this accident. Only a fraction remained in the orbita; the residual chopstick got lost. Hence, the substance of the chopstick was unknown. Computed tomography (CT) revealed a foreign body in the right orbita, but ophthalmologists had initially no indication of intervention. Further course according to the follow-up CT showed an increase of Hounsfield units (HU). These findings led to the assumption that the foreign body was made of wood. Through this, the ophthalmologists performed an evacuation. Motivated by these clinical results, we created an experimental setup that could demonstrate changes of HU in different coated chopsticks. It is concluded that wooden foreign bodies can display a variety of CT appearances depending on materials, types, coating, and time-course. PMID- 17347768 TI - Sonographic diagnosis of pneumoperitoneum using the 'enhancement of the peritoneal stripe sign.' A prospective study. AB - The objective of this study was to validate the Enhanced Peritoneal Stripe Sign (EPSS) in diagnosing pneumoperitoneum in patients presenting with acute abdomen. The EPSS was described as a specific sonographic sign of pneumoperitoneum in an animal model and few patients who had undergone laparoscopy (Muradali et al. in Am J Roentgenol 173(5): 1257-1262, 1999). This is the first large-scale study in patients to detect the efficacy of EPSS. Six hundred consecutive patients with acute abdominal pain presenting to the author over a period of 3 months in the emergency ultrasonography department were prospectively studied for the presence of the EPSS. As part of their clinical work up, patients also underwent plain radiographs and/or a computed tomography (CT) of the abdomen. The author was unaware of the results of other imaging studies at the time of the sonographic examination. In all cases, the final diagnosis was based on the intra-operative findings, results of other imaging techniques and clinical follow-up. Based on the final diagnosis, 21 out of 600 patients had pneumoperitoneum. The EPSS was found to be positive in all 21 of these patients. Another three patients were found to have the sign false positive. There were no false negatives in this study. The EPSS thus had a sensitivity of 100%, a specificity of 99%, a positive predictive value of 87.5% and a negative predictive value of 100%. The EPSS is a reliable and accurate sonographic sign for the diagnosis of pneumoperitoneum. It should be looked for in all patients presenting with acute abdominal pain. PMID- 17347769 TI - A Chinese isolate of barley yellow dwarf virus-PAV represents a third distinct species within the PAV serotype. AB - The complete nucleotide sequence of barley yellow dwarf virus (BYDV) PAV-CN genomic RNA was determined. This represents the seventh complete genome sequence of a BYDV-PAV serotype. The genome organization of PAV-CN was comparable to that of other BYDV-PAV serotypes, but the nucleotide sequence of full genome was only 76.9-80.3% similar. Sequence similarity of individual open reading frames and untranslated regions (UTR) between PAV-CN and other PAV isolates ranged from 37.9 to 98.2%. Overall, PAV-CN was most similar to BYDV-PAS, which belongs to one of two distinct species within the PAV serotype of BYDV, although the 5' UTR and ORF1 of PAV-CN was most similar to BYDV-GAV, another member of the genus Luteovirus that is not serologically related to BYDV-PAV. These data suggest that PAV-CN may have undergone a recombination event with GAV and that PAV-CN represents a third distinct species within the PAV serotype of BYDV. PMID- 17347770 TI - Induction of apoptosis by iridovirus virion protein extract. AB - Chilo iridescent virus (CIV; IIV-6) is the type member of the genus Iridovirus (family Iridoviridae, large icosahedral cytoplasmic DNA viruses). CIV induces death and deformity in the cotton boll weevil, Anthonomus grandis, replicates productively in larvae of the cotton boll weevil, and significantly reduces laboratory populations of the cotton aphid, Aphis gossypii. CIV virion protein extract (CVPE) shuts down host protein synthesis in several insect cell lines and induces mortality in neonate boll weevil larvae. We report here that CVPE induces apoptosis in spruce budworm and boll weevil cell lines, as detected by blebbing, DNA fragmentation, and TUNEL assay. Tissue culture toxicity dose assays (TCTD(50)) showed that spruce budworm cells were eight times more sensitive to CVPE than boll weevil cells. Pancaspase inhibitor suppressed apoptosis but had marginal effect on inhibition of host protein synthesis. Moreover, the CVPE dose for apoptosis was 1000-fold lower than the dose for shutdown of host synthesis. We also detected protein kinase activity in CVPE. Heating CVPE at 60 degrees C for 30 min destroyed all three activities. Our results suggest that one or more polypeptides in CIV induce apoptosis. This is the first study demonstrating apoptosis induction by a member of the genus Iridovirus and by virion extracts of a member of the family Iridoviridae. PMID- 17347771 TI - Identification of new isolates of Turnip mosaic virus that cluster with less common viral strains. AB - Turnip mosaic virus (TuMV) was found infecting cultivated brassicas and wild and cultivated ornamental Brassicaceae plants in different regions of Spain. Five new TuMV isolates, originating from different host plant species (Brassica cretica, Brassica juncea, Brassica napus, Eruca vesicaria subsp. sativa and Sisymbrium orientale), have been identified. The nucleotide sequences of the coat protein (CP) genes of the five isolates were determined. Phylogenetic analysis of the CP sequences showed that the five isolates grouped into two different clusters. The three isolates from the central region of Spain clustered with a previously reported Pisum sativum isolate from southeastern Spain, whereas the other two isolates from the eastern region clustered with two Italian and two Greek isolates. Both clusters were genetically distinct and belonged to the multi lineage group OBR. The OBR group contains mainly TuMV isolates from hosts other than Brassica spp. and Raphanus sativus and mostly originating from Mediterranean countries. These new sequences provide further phylogenetic resolution of the OBR group. Although new TuMV isolates have been found in Spain, they were not associated with any serious disease outbreaks. PMID- 17347772 TI - The complete nucleotide sequence of a mild strain of Bean yellow dwarf virus. PMID- 17347773 TI - Characterization and transient replication of tomato leaf curl virus defective DNAs. AB - Distinct subgenomic DNA species known as defective (df) DNA molecules were found in plants infected with tomato leaf curl virus (TLCV). Four df DNAs derived from TLCV Type and Darwin 1 strains were found to contain large deletions that disrupt all of the viral genes required for viral replication, encapsidation and spread. However, the viral origin of replication (ori), including the replication associated protein (Rep) binding domains, was present in all four df DNAs. Co agroinfection of leaf strips with tandem repeat constructs of the viral and df DNAs resulted in their replication in the presence of the respective TLCV strain. However, the df DNAs failed to move in whole plants when co-inoculated with TLCV. The df DNAs were shown to be associated with TLCV coat protein, which may indicate encapsidation. Mutational analysis showed the minimum sequence requirements for df DNA replication by TLCV to be the intergenic region containing the Rep-binding domains. PMID- 17347774 TI - Dopaminergic contribution to cognitive sequence learning. AB - Evidence suggests that dopaminergic mechanisms in the basal ganglia are important in feedback-guided habit learning. To test hypothesis, we assessed cognitive sequence learning in 120 healthy volunteers and measured plasma levels of homovanillic acid [HVA] (a metabolite of dopamine), 5-hydroxyindoleacetic acid [5 HIAA] (a metabolite of serotonin), and 3-methoxy-4-hydroxypheylglycol [MHPG] (a metabolite of norepinephrine). Results revealed a significant negative relationship between errors in the feedback-guided training phase of the sequence learning task and the plasma HVA level. The HVA level accounted for 10.5% of variance of performance. Participant who had lower HVA level than the median value of the whole sample committed more errors during the training phase compared with participants who had higher HVA plasma level than the median value. A similar phenomenon was not observed for the context-dependent phase of the task and for 5-HIAA and MHPG. These results suggest that dopamine plays a special role in feedback-guided cognitive sequence learning. PMID- 17347775 TI - Quantitative detection of circulating epithelial cells by Q-RT-PCR. AB - INTRODUCTION: It has been shown that the quantity of circulating tumor cells (CTCs) in breast cancer patients is an independent predictor of survival and treatment response. Real time quantitative reverse transcriptase PCR (Q-RT-PCR) is a sensitive technique for detection of CTCs. Our aim was to investigate whether the technique can be used also to quantitate these CTCs. METHODS: We tested cytokeratin 19 (CK19), maspin, mammaglobin, GAPDH and RPL19 genes for their level of expression and linearity of amplification in serial dilutions of RNA extracted from the MDA-MB-231, UACC-812, T47D and HS578T breast cancer cell lines. To simulate CTCs, serial dilutions of cultured T47D and HS578T cells were added to peripheral blood from healthy volunteers. The samples were subjected to enrichment, RNA extraction and Q-RT-PCR. RESULTS: CK19 was reliably expressed in all four cell lines with a linear relationship between the quantity of added cells and the amount of CK19 RNA. The lower limit of reliable detection was 5 cells per sample, which corresponds to a concentration of 0.7 cell/ml in 7.5 ml of blood or would translate to a lower CTC concentration in a larger volume of blood. CONCLUSION: This technique may prove useful for high throughput comparative quantification of CTCs in individual patients during treatment and subsequent follow up for research and clinical management purposes. PMID- 17347776 TI - Decreased levels of hypoxic cells in gefitinib treated ER+ HER-2 overexpressing MCF-7 breast cancer tumors are associated with hyperactivation of the mTOR pathway: therapeutic implications for combination therapy with rapamycin. AB - Developing novel synergistic and more effective combination treatments is necessary for better management of breast cancer in the clinic. It is established that HER-2 overexpressing breast cancers are sensitive to the HER-1 (epidermal growth factor receptor (EGFR)) inhibitor gefitinib, but that this targeted agent produces only moderate therapeutic effects in vivo. Here, we use a model of ER(+) HER-2 overexpressing MCF-7 breast cancer (MCF-7(HER-2)) to identify, as broadly as possible, the in vivo microenvironmental and molecular therapeutic responses to gefitinib to predict a therapeutically viable target for gefitinib-based combination treatment. Our data show a link between in vivo reductions in tumor hypoxia (3-fold decrease, P = 0.002) and elevated activity of the mTOR pathway (3.8-fold increase in phospho-p70-S6K protein, P = 0.006) in gefitinib treated MCF-7(HER-2) tumors. Despite decreased levels of phosphorylated EGFR, HER-2 and Erk1/2 (P = 0.081, 0.005 and 0.034, respectively) the expression of phospho-AKT was not reduced in MCF-7(HER-2) tumors after gefitinib treatment. Levels of ERalpha receptor were, however, 1.8-fold higher in gefitinib treated compared to control tumors (P = 0.008). Based on these results we predict that gefitinib activity against ER(+) HER-2 overexpressing EGFR co-expressing breast cancers should be enhanced if used with agents that target the mTOR pathway. In vitro studies using MCF-7(HER-2) and BT474 breast cancer cells exposed to gefitinib and rapamycin in combination show that this combination produced significantly greater growth inhibitory effects than either of the drugs alone. Chou and Talalay analysis of the data suggested that combination of gefitinib and rapamycin was synergistic (CI < 1) at a number of selected drug ratios and over a broad range of effective doses. PMID- 17347777 TI - Changes in pitch with a cochlear implant over time. AB - In the normal auditory system, the perceived pitch of a tone is closely linked to the cochlear place of vibration. It has generally been assumed that high-rate electrical stimulation by a cochlear implant electrode also evokes a pitch sensation corresponding to the electrode's cochlear place ("place" code) and stimulation rate ("temporal" code). However, other factors may affect electric pitch sensation, such as a substantial loss of nearby nerve fibers or even higher level perceptual changes due to experience. The goals of this study were to measure electric pitch sensations in hybrid (short-electrode) cochlear implant patients and to examine which factors might contribute to the perceived pitch. To look at effects of experience, electric pitch sensations were compared with acoustic tone references presented to the non-implanted ear at various stages of implant use, ranging from hookup to 5 years. Here, we show that electric pitch perception often shifts in frequency, sometimes by as much as two octaves, during the first few years of implant use. Additional pitch measurements in more recently implanted patients at shorter time intervals up to 1 year of implant use suggest two likely contributions to these observed pitch shifts: intersession variability (up to one octave) and slow, systematic changes over time. We also found that the early pitch sensations for a constant electrode location can vary greatly across subjects and that these variations are strongly correlated with speech reception performance. Specifically, patients with an early low-pitch sensation tend to perform poorly with the implant compared to those with an early high-pitch sensation, which may be linked to less nerve survival in the basal end of the cochlea in the low-pitch patients. In contrast, late pitch sensations show no correlation with speech perception. These results together suggest that early pitch sensations may more closely reflect peripheral innervation patterns, while later pitch sensations may reflect higher-level, experience-dependent changes. These pitch shifts over time not only raise questions for strict place-based theories of pitch perception, but also imply that experience may have a greater influence on cochlear implant perception than previously thought. PMID- 17347778 TI - The CLIC1 chloride channel is regulated by the cystic fibrosis transmembrane conductance regulator when expressed in Xenopus oocytes. AB - CLIC proteins comprise a family of chloride channels whose physiological roles are uncertain. To gain further insight into possible means of CLIC1 channel activity regulation, this protein was expressed in Xenopus oocytes alone or in combination with the cystic fibrosis transmembrane conductance regulator (CFTR). Whole-cell currents were determined using two-electrode voltage-clamp methods. Expression of CLIC1 alone did not increase whole-cell conductance either at rest or in response to increased intracellular cyclic adenosine monophosphate (cAMP). However, expression of CLIC1 with CFTR led to increased cAMP-activated whole-cell currents compared to expression from the same amount of CFTR mRNA alone. IAA-94 is a drug known to inhibit CLIC family channels but not CFTR. In oocytes expressing both CLIC1 and CFTR, a fraction of the cAMP-activated whole-cell current was sensitive to IAA-94, whereas in oocytes expressing CFTR alone, the cAMP-stimulated current was resistant to the drug. Cell fractionation studies revealed that the presence of CFTR conferred cAMP-stimulated redistribution of a fraction of CLIC1 from a soluble to a membrane-associated form. We conclude that when expressed in Xenopus oocytes CFTR confers cAMP regulation to CLIC1 activity in the plasma membrane and that at least part of this regulation is due to recruitment of CLIC1 from the cytoplasm to the membrane. PMID- 17347779 TI - An emulsion of sulfoquinovosylacylglycerol with long-chain alkanes increases its permeability to tumor cells. AB - The alpha-anomer form of sulfoquinovosyl-monoacylglycerol with a saturated C18 fatty acid (alpha-SQMG-C(18:0)) is a natural sulfolipid that is a clinically promising antitumor agent. It forms vesicles, micelles or an emulsion in water, depending on several physicochemical conditions. The type of aggregate formed appears to strongly influence the bioactivity level. Thus, we investigated the nature of the aggregates in relation to their bioactivities. The structure of the alpha-SQMG-C(18:0) assembly was greatly affected by the type of additive used in the preparation. Emulsification with ethanol and n-decane might be more effective at inhibiting tumor cell growth than the micelle or vesicle preparations. alpha SQMG-C(18:0) formed an "emulsion-like-aggregate" in ethanol containing an n decane concentration in the range of 1.03-103 mM: . These ethanol/n-alkane/alpha SQMG-C(18:0) aggregates inhibited cell growth in a dose-dependent manner, under optimum conditions (i.e., ethanol containing 103 mM: of n-decane or n-dodecane dispersed in phosphate-buffered saline or culture medium). Based on these data, we discuss the relationship between the molecular action of and antitumor activity by alpha-SQMG-C(18:0). PMID- 17347780 TI - Effect of alloxan diabetes and subsequent insulin treatment on temperature kinetics properties of succinate oxidase activity in rat kidney mitochondria. AB - Early and late effects of alloxan diabetes and subsequent treatment with insulin on the temperature kinetics properties of succinate oxidase (SO) activity in rat kidney mitochondria were examined. In diabetic animals SO activity increased significantly and the increase was more pronounced at the late stage. Insulin treatment partially restored SO activity. However, the effect was temperature dependent. In diabetic animals the energy of activation in the low temperature range (E(L)) increased significantly while that in the high temperature range (E(H)) decreased. The latter seems to be responsible for improving catalytic efficiency in the diabetic state. Insulin treatment normalized E(H) only in the 1 month diabetic group. The phase transition temperature (Tt), decreased in diabetic animals. Insulin treatment caused an increase beyond the control value in Tt in 1-month diabetic animals. The results suggest that insulin status dependent modulation of SO activity is a complex process. PMID- 17347781 TI - Functional expression of inward rectifier potassium channels in cultured human pulmonary smooth muscle cells: evidence for a major role of Kir2.4 subunits. AB - Strong inwardly rectifying K(+) (K(IR)) channels that contribute to maintaining the resting membrane potential are encoded by the Kir2.0 family (Kir2.1-2.4). In smooth muscle, K(IR) currents reported so far have the characteristics of Kir2.1. However, Kir2.4, which exhibits unique characteristics of barium block, has been largely overlooked. Using patch-clamp techniques, we characterized K(IR) channels in cultured human pulmonary artery smooth muscle (HPASM) cells and compared them to cloned Kir2.1 and Kir2.4 channels. In a physiological K(+) gradient, inwardly rectifying currents were observed in HPASM cells, the magnitude and reversal potential of which were sensitive to extracellular K(+) concentration. Ba(2+) (100 microM ) significantly inhibited inward currents and depolarized HPASM cells by approximately 10 mV. In 60 mM extracellular K(+), Ba(2+) blocked K(IR) currents in HPASM cells with a 50% inhibitory concentration of 39.1 microM at 100 mV compared to 3.9 microM and 65.6 microM for Kir2.1 and Kir2.4, respectively. Cloned Kir2.4 and K(IR) currents in HPASM cells showed little voltage dependence to Ba(2+) inhibition, which blocked at a more superficial site than for Kir2.1. Single-channel recordings revealed strong inwardly rectifying channels with an average conductance of 21 pS in HPASM cells, not significantly different from either Kir2.1 (19.6 pS) or Kir2.4 (19.4 pS). Reverse-transcription polymerase chain reaction detected products corresponding to Kir2.1, Kir2.2 and Kir2.4 but not Kir2.3. We demonstrate that cultured HPASM cells express K(IR) channels and suggest both Kir2.1 and Kir2.4 subunits contribute to these channels, although the whole-cell current characteristics described share more similarity with Kir2.4. PMID- 17347782 TI - The third sodium binding site of Na,K-ATPase is functionally linked to acidic pH activated inward current. AB - Sodium- and potassium-activated adenosine triphosphatases (Na,K-ATPase) is the ubiquitous active transport system that maintains the Na(+) and K(+) gradients across the plasma membrane by exchanging three intracellular Na(+) ions against two extracellular K(+) ions. In addition to the two cation binding sites homologous to the calcium site of sarcoplasmic and endoplasmic reticulum calcium ATPase and which are alternatively occupied by Na(+) and K(+) ions, a third Na(+) specific site is located close to transmembrane domains 5, 6 and 9, and mutations close to this site induce marked alterations of the voltage-dependent release of Na(+) to the extracellular side. In the absence of extracellular Na(+) and K(+), Na,K-ATPase carries an acidic pH-activated, ouabain-sensitive "leak" current. We investigated the relationship between the third Na(+) binding site and the pH activated current. The decrease (in E961A, T814A and Y778F mutants) or the increase (in G813A mutant) of the voltage-dependent extracellular Na(+) affinity was paralleled by a decrease or an increase in the pH-activated current, respectively. Moreover, replacing E961 with oxygen-containing side chain residues such as glutamine or aspartate had little effect on the voltage-dependent affinity for extracellular Na(+) and produced only small effects on the pH activated current. Our results suggest that extracellular protons and Na(+) ions share a high field access channel between the extracellular solution and the third Na(+) binding site. PMID- 17347783 TI - Language development at ten months. Predictive of language outcome and school achievement ten years later? AB - AIMS: Language development was followed from infancy to primary school age in order to examine the predictive significance for later language and scholastic outcome. METHODS: Participants were from a prospective longitudinal study of a birth cohort of initially 362 children. A subsample of 90 children (54 boys, 36 girls) was administered with the Receptive-Expressive Emergent Language Scale (REEL) in order to obtain age-appropriate measures of expressive and receptive language at the age of 10 months. At 11 years, children completed a comprehensive test battery assessing various intellectual skills and language performance. Scholastic measures included a school performance score and a recommendation for type of secondary school. RESULTS: Both expressive and receptive language performance at 10 months were significantly associated with cognitive and educational outcome 10 years later. Infant language performance not only predicted later verbal and nonverbal skills but also school achievement at the end of primary school. Prediction was higher in girls than in boys and slightly better for verbal and academic than for nonverbal performance. CONCLUSIONS: The results demonstrate the importance of early language abilities in predicting cognitive and academic outcome at school age. PMID- 17347784 TI - An annotated bibliography of C.J. van der Klaauw with notes on the impact of his work. AB - Van der Klaauw was a professor of Descriptive Zoology in the period 1934-1958. This paper presents a concise annotated overview of his publications. In his work three main topics can be recognized: comparative anatomy of the mammalian auditory region, theoretical studies about ecology and ecological morphology, and vertebrate functional morphology. In particular van der Klaauw developed new concepts on functional morphology, based upon a holistic approach. A series of studies in functional morphology of Vertebrates by his students is added. An overview of recent morphological and theoretical studies show that this new approach had a long lasting impact in studies of functional morphology. PMID- 17347785 TI - Natural genome-editing competences of viruses. AB - It is becoming increasingly evident that the driving forces of evolutionary novelty are not randomly derived chance mutations of the genetic text, but a precise genome editing by omnipresent viral agents. These competences integrate the whole toolbox of natural genetic engineering, replication, transcription, translation, genomic imprinting, genomic creativity, enzymatic inventions and all types of genetic repair patterns. Even the non-coding, repetitive DNA sequences which were interpreted as being ancient remnants of former evolutionary stages are now recognized as being of viral descent and crucial for higher-order regulatory and constitutional functions of protein structural vocabulary. In this article I argue that non-randomly derived natural genome editing can be envisioned as (a) combinatorial (syntactic), (b) context-specific (pragmatic) and (c) content-sensitive (semantic) competences of viral agents. These three-leveled biosemiotic competences could explain the emergence of complex new phenotypes in single evolutionary events. After short descriptions of the non-coding regulatory networks, major viral life strategies and pre-cellular viral life three of the major steps in evolution serve as examples: There is growing evidence that natural genome-editing competences of viruses are essential (1) for the evolution of the eukaryotic nucleus, (2) the adaptive immune system and (3) the placental mammals. PMID- 17347786 TI - The role of Frank elasticity in cholesteric elastomers. AB - The effect of Frank elasticity on deformations of cholesteric elastomers by mechanical stress applied perpendicular to the helix axis is studied by numerical minimization of the free energy. Above a critical strain, a solution with an only oscillating director is found to be stable in comparison to a distorted helix. At the critical strain, the contractions perpendicular to stress change discontinuously. The critical strain is found to increase with increasing Frank elasticity contribution to the free energy density, and to diverge when the conformation anisotropy of the polymer backbone vanishes. The results are compared with recent experiments which indicated that, in case of weak conformation anisotropies, the Frank elasticity contribution to the free energy cannot be neglected. PMID- 17347787 TI - Impact of receptor-ligand distance on adhesion cluster stability. AB - Cells in multicellular organisms adhere to the extracellular matrix through two dimensional clusters spanning a size range from very few to thousands of adhesion bonds. For many common receptor-ligand systems, the ligands are tethered to a surface via polymeric spacers with finite binding range, thus adhesion cluster stability crucially depends on receptor-ligand distance. We introduce a one-step master equation which incorporates the effect of cooperative binding through a finite number of polymeric ligand tethers. We also derive Fokker-Planck and mean field equations as continuum limits of the master equation. Polymers are modeled either as harmonic springs or as worm-like chains. In both cases, we find bistability between bound and unbound states for intermediate values of receptor ligand distance and calculate the corresponding switching times. For small cluster sizes, stochastic effects destabilize the clusters at large separation, as shown by a detailed analysis of the stochastic potential resulting from the Fokker-Planck equation. PMID- 17347788 TI - Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis. AB - Telomere length decreases with age and is associated with osteoblast senescence. In 2,150 unselected women, leukocyte telomere length was significantly correlated with bone mineral density. Clinical osteoporosis was associated with shorter telomeres, suggesting that telomere length can be used as a marker of bone aging. INTRODUCTION: The length of telomeres in proliferative cells diminishes with age. Telomere shortening and telomerase activity have been linked to in vitro osteoblast senescence and to increased secretion of pro-inflammatory cytokines. We explored whether bone mineral density correlates with telomere length in leukocytes. MATERIALS AND METHODS: The relationship between leukocyte telomere length, bone mineral density (BMD) and osteoporosis (as defined by the World Health Organization) was examined in a cohort of 2,150 women from a population based twin cohort aged 18-79. RESULTS: After adjusting for age, body mass index, menopausal status, smoking, hormone replacement therapy status, telomere length was positively correlated with BMD of the spine (p < 0.005), forearm (p < 0.013), but not the femoral neck (p < 0.06). Longer telomeres were associated with reduced the risk of clinical OP at two or more sites (odds ratio = 0.594 95% CI 0.42-0.84 p < 0.003) and in women over the age of 50, clinical osteoporosis was associated with 117 bp shorter telomere length (p < 0.02) equivalent to 5.2 years of telomeric aging. CONCLUSIONS: Shortened leukocyte telomere length is independently associated with a decrease in BMD and the presence of osteoporosis in women. Our data provide evidence that leukocyte telomere length could be a marker of biological aging of bone. PMID- 17347789 TI - Low bone mineral density in COPD patients related to worse lung function, low weight and decreased fat-free mass. AB - Low bone mineral density is frequently seen in COPD patients. Advanced COPD, low BMI and muscle depletion are risk factors for developing low bone mineral density (BMD). Low bone mineral density is seen in 75% of the GOLD stage IV patients. INTRODUCTION: We set out to investigate the prevalence of low bone mineral density (BMD) in chronic obstructive pulmonary disease (COPD) as well as the predictors of abnormal bone mineral density. METHODS: A cross-sectional design was used to evaluate 115 subjects with COPD (GOLD stages II-IV). Bone mineral density (BMD) was measured using an ultrasound densitometer. The forced expiratory volume in 1 s (FEV(1)) was assessed and fat-free mass was measured using bioelectrical impedance analysis. Chi-square tests and logistic regression were used for analysis. RESULTS: The prevalence of a T-score < -1.0 SD and > -2.5 SD was 28.6% in GOLD stage II, 40.3% in GOLD stage III and 57.1% in GOLD stage IV. The prevalence of a T-score 20, and the reactive empirical bond order Brenner potential for C-C interactions is also revised to include the effect of the metal atoms on such interactions. PMID- 17347825 TI - Interaction of copper organometallic precursors with barrier layers of Ti, Ta and W and their nitrides: a first-principles molecular dynamics study. AB - Processes for the deposition of copper films on transition metal barrier layers by means CVD using organometallic precursors are often found to lead to poor adhesion characteristics of the grown film. By means of first-principles molecular dynamics simulations, we show that the source of the problem is the strong reactivity of the surfaces toward the precursors, which decompose spontaneously upon contact with the surface leading to contamination of the interface. Our simulations consider Ti, Ta, and W as barrier layers, and Cu(hfac) (tmvs) as precursor. In contrast, we show that surfaces of these metals properly passivated with nitrogen, in such a way that only N atoms are exposed on the surface, are much less active and do not lead to decomposition of the precursor. We propose this passivation procedure as a practical solution to the adhesion problem. PMID- 17347826 TI - Intensive Care Medicine and the "Cenacle principles". PMID- 17347827 TI - Glycine and ammonia plasma concentrations during sedation with remifentanil in critically ill patients. AB - OBJECTIVES: To investigate glycine and ammonia plasma concentrations during a 72 h remifentanil infusion and the relationship between glycine concentration and remifentanil infusion rate. DESIGN AND SETTING: A prospective open-label observational clinical trial in a trauma and a neurosurgical intensive care unit in a university teaching hospital. PATIENTS: Nine consecutive patients requiring sedation and ventilatory support for at least 72 h. One was excluded due to acute cardiac failure. INTERVENTIONS: Patients were sedated with remifentanil and propofol. Glycine and ammonia plasma concentrations were measured every 12 h during an intravenous remifentanil infusion performed over 72 h, and 24 h after the end of the infusion. Cumulative remifentanil dose and rate of infusion were recorded for each patient. Clinical and biological signs of glycine toxicity were evaluated. MEASUREMENTS AND RESULTS: Glycine and ammonia plasma concentrations did not exceed the toxic threshold at any time. Plasma glycine concentration measured at the end of remifentanil infusion was significantly correlated with the mean weighted rate of remifentanil infusion and with the cumulative remifentanil dose. A correlation between plasma glycine concentration and creatinine clearance at the end of remifentanil infusion was also documented. CONCLUSIONS: Plasma glycine concentration was correlated with the remifentanil cumulative dose and the infusion rate and did not reach the toxic threshold. As glycine concentration was also correlated with creatinine clearance and because remifentanil was the only source of exogenous glycine, additional data are necessary to ascertain the safety of remifentanil infusion in ICU patients. PMID- 17347828 TI - Single rooms may help to prevent nosocomial bloodstream infection and cross transmission of methicillin-resistant Staphylococcus aureus in intensive care units. AB - OBJECTIVE: Nosocomial infections remain a major problem in intensive care units. Several authorities have recommended housing patients in single rooms to prevent cross-transmission of potential pathogens, but this issue is currently debated. The aim of the present study was to compare the rate of nosocomial cross contamination between patients hosted in single rooms versus bay rooms. DESIGN: Prospective observational data acquisition over 2.5 years. SETTING: A 14-bed medico-surgical ICU, composed of six single-bed rooms plus a six-bed and a two bed bay room served by the same staff. PATIENTS AND PARTICIPANTS: All patients admitted from 1 July 2002 to 31 December 2004. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in admitted patients was 1.1% and acquisition rate 2.4%. The incidence density of MRSA acquisition was 4.1 [95% CI 2.7-6.3]/1,000 patient-days in bay rooms versus 1.3 [0.5-3.4]/1,000 patient-days in single rooms (p<0.001). Pseudomonas spp. acquisition rate was 3.9 [2.5-6.1]/1,000 patient-days in bay rooms versus 0.7 [0.2-2.4]/1,000 patient-days in single rooms (p<0.001), and Candida spp. colonization was 38.4 [33.3-44.1]/1,000 patient-days in bay rooms versus 13.8 [10.2-18.6]/1,000 patient-days (p<0.001). By multivariate analysis, the relative risk of MRSA, Pseudomonas aeruginosa and Candida spp. acquisition in single rooms or cubicles versus bay rooms was 0.65, 0.61 and 0.75 respectively. CONCLUSIONS: These data suggest that in an institution where MRSA is not hyperendemic, infection control measures may be more effective to prevent cross-transmission of microorganisms in patients housed in single rooms. PMID- 17347829 TI - Iron deficiency in rice shoots: identification of novel induced genes using RDA and possible relation to leaf senescence. AB - Rice plants are highly susceptible to Fe-deficiency. Under nutrient deprivation, plant cells undergo extensive metabolic changes for their continued survival. To provide further insight into the pathways induced during Fe-deficiency, rice seedlings were grown for 3, 6 and 9 days in the presence or absence of Fe. Using RDA (Representational Difference Analysis), sequences of 32 induced genes in rice shoots under Fe-deficiency were identified. About 30% of the sequences found have been previously reported as responsive to other abiotic and even biotic stresses. However, this is the first report that indicates their relation to Fe deprivation. Differential expression of selected genes was confirmed by semi quantitative RT-PCR analysis. The identification of classical senescence-related sequences, such as lipase EC 3.1.1.-, ubiquitin-conjugating enzyme EC 6.3.2.19, beta-Glucosidase EC 3.2.1.21 and cysteine synthase EC 2.5.1.47, besides the higher accumulation of total soluble sugars prior to the decrease of total chlorophyll content in Fe-deficient leaves, indicate that sugar accumulation may be one of the factors leading to premature leaf senescence induced by Fe deficiency. PMID- 17347830 TI - Anoxia-induced changes in reactive oxygen species and cyclic nucleotides in the painted turtle. AB - The Western painted turtle survives months without oxygen. A key adaptation is a coordinated reduction of cellular ATP production and utilization that may be signaled by changes in the concentrations of reactive oxygen species (ROS) and cyclic nucleotides (cAMP and cGMP). Little is known about the involvement of cyclic nucleotides in the turtle's metabolic arrest and ROS have not been previously measured in any facultative anaerobes. The present study was designed to measure changes in these second messengers in the anoxic turtle. ROS were measured in isolated turtle brain sheets during a 40-min normoxic to anoxic transition. Changes in cAMP and cGMP were determined in turtle brain, pectoralis muscle, heart and liver throughout 4 h of forced submergence at 20-22 degrees C. Turtle brain ROS production decreased 25% within 10 min of cyanide or N(2) induced anoxia and returned to control levels upon reoxygenation. Inhibition of electron transfer from ubiquinol to complex III caused a smaller decrease in [ROS]. Conversely, inhibition of complex I increased [ROS] 15% above controls. In brain [cAMP] decreased 63%. In liver [cAMP] doubled after 2 h of anoxia before returning to control levels with prolonged anoxia. Conversely, skeletal muscle and heart [cAMP] remained unchanged; however, skeletal muscle [cGMP] became elevated sixfold after 4 h of submergence. In liver and heart [cGMP] rose 41 and 127%, respectively, after 2 h of anoxia. Brain [cGMP] did not change significantly during 4 h of submergence. We conclude that turtle brain ROS production occurs primarily between mitochondrial complexes I and III and decreases during anoxia. Also, cyclic nucleotide concentrations change in a manner suggestive of a role in metabolic suppression in the brain and a role in increasing liver glycogenolysis. PMID- 17347831 TI - Diffuse idiopathic skeletal hyperostosis as a cause of acute respiratory distress in early postoperative period of total knee arthroplasty. AB - Diffuse idiopathic skeletal hyperostosis (DISH) is a common disorder among the elderly. The diagnosis is made on radiological findings and most of the cases are asymptomatic. In the cases with spinal involvement, bridging ossification of the anterior longitudinal ligament is a common finding. We report a case of DISH, who developed respiratory distress after bilateral total knee arthroplasty operation. The acute occurrence of symptoms after general anesthesia is a rare manifestation of the disease. Radiological findings and the result of surgical resection of anterior cervical osteophytes are discussed. PMID- 17347832 TI - Asymmetrical bilateral traumatic hip dislocation in an adult with bilateral acetabular fracture. AB - This case report aims at presenting a unique case of simultaneous bilateral traumatic dislocation with right side anterior and the left side posterior together with bilateral acetabular fracture. Under general anesthesia, closed reduction of both hips was carried out. The case presented represents an unusual, severe combination of injuries resulting from a high-speed motor-vehicle accident. Traumatic hip dislocation represents a true orthopedic emergency. Given the severity of the associated complications, every effort should be made to ensure prompt diagnosis and immediate therapy. PMID- 17347833 TI - Control of presacral venous bleeding, using thumbtacks. AB - BACKGROUND: Massive life threatening bleeding from presacral venous plexus in gynecological surgery, though uncommon can be fatal when conventional methods fail. CASE: In the present case, a 55-year-old woman undergoing radical hysterectomy for cancer cervix was saved using thumbtacks to control bleeding from presacral vessels when conventional methods were ineffective. CONCLUSION: Use of thumbtacks in such patients is simple, cost effective and life saving. PMID- 17347834 TI - Climate change and heat-related mortality in six cities part 1: model construction and validation. AB - Heat waves are expected to increase in frequency and magnitude with climate change. The first part of a study to produce projections of the effect of future climate change on heat-related mortality is presented. Separate city-specific empirical statistical models that quantify significant relationships between summer daily maximum temperature (T (max)) and daily heat-related deaths are constructed from historical data for six cities: Boston, Budapest, Dallas, Lisbon, London, and Sydney. 'Threshold temperatures' above which heat-related deaths begin to occur are identified. The results demonstrate significantly lower thresholds in 'cooler' cities exhibiting lower mean summer temperatures than in 'warmer' cities exhibiting higher mean summer temperatures. Analysis of individual 'heat waves' illustrates that a greater proportion of mortality is due to mortality displacement in cities with less sensitive temperature-mortality relationships than in those with more sensitive relationships, and that mortality displacement is no longer a feature more than 12 days after the end of the heat wave. Validation techniques through residual and correlation analyses of modelled and observed values and comparisons with other studies indicate that the observed temperature-mortality relationships are represented well by each of the models. The models can therefore be used with confidence to examine future heat-related deaths under various climate change scenarios for the respective cities (presented in Part 2). PMID- 17347835 TI - Efficacy of steroid pulse, plasmapheresis, and mizoribine in a patient with focal segmental glomerulosclerosis. AB - There have been few reports on successful treatment for focal segmental glomerulosclerosis (FSGS) complicated by leukoencephalopathy. We report the efficacy of the steroid pulse and mizoribine (MZB) combined with plasmapheresis (PP) for a case of FSGS with leukoencephalopathy induced by cyclosporine (CyA). The patient was a 4-year-old boy with FSGS who presented with steroid-resistant nephrotic syndrome (NS) and was treated with CyA. On the 7th day after starting CyA, he complained of one visual disorder, and hypertension and tonic convulsions were observed. Electroencephalography (EEG) revealed generalized slow waves, and magnetic resonance imaging (MRI) disclosed high signal intensity in the white matter. A diagnosis of leukoencephalopathy induced by CyA was made on the basis of these findings with the improvement in clinical manifestations upon discontinuation of CyA. We treated the patient with steroid pulse therapy and MZB combined with PP, and the proteinuria gradually decreased and only microscopic hematuria remained. We report that steroid pulse and MZB combined with PP may be an effective treatment in a patient with FSGS complicated by CyA-induced leukoencephalopathy. PMID- 17347836 TI - Genetics of focal segmental glomerulosclerosis. AB - The recent advances in understanding the pathophysiology of focal segmental glomerulosclerosis (FSGS) and molecular function of glomerular filtration barrier come directly from genetic linkage and positional cloning studies. The exact role and function of the newly discovered genes and proteins are being investigated by in vitro and in vivo mechanistic studies. Those genes and proteins interactions seem to change susceptibility to kidney disease progression. Better understanding of their exact role in the development of FSGS may influence future therapies and outcomes in this complex disease. PMID- 17347838 TI - Laparoscopic pyeloplasty is feasible for lower pole pelvi-ureteric obstruction in duplex systems. AB - Exclusive lower pole pelvi-ureteric junction obstruction (PUJO) in double collecting systems in children is a rare condition requiring reconstructive surgery. We report on the feasibility of laparoscopic transabdominal dismembered pyeloplasty in two cases. Two children with duplicated collecting systems presented with hydronephrosis of lower pole moiety due to exclusive PUJO. Isotope renography revealed impaired drainage of affected lower kidney pole. A four trocar transabdominal technique was used. No stent was used in one patient with bilateral duplication (male, 6 years) while a 4 Fr. double-J stent was placed laparoscopically in another with unilateral duplication (male, 9 months). Both patients had uneventful laparoscopic transabdominal dismembered pyeloplasty. The operation time was 115 and 155 min, respectively, and was comparable to our previously reported patient series undergoing laparoscopic pyeloplasty for singular collecting systems. After a mean follow-up of 21 months (range 12-42), both patients were asymptomatic and showed improved pelvi-ureteric drainage on isotope renography and improved hydronephrosis on ultrasound scan. Laparoscopic transabdominal dismembered pyeloplasty is safe and effective in children with rare lower pole PUJO in double collecting systems. PMID- 17347837 TI - Aquaporin-4 and brain edema. AB - Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid (CSF) and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. Experiments using AQP4-null mice provide strong evidence for AQP4 involvement in cerebral water balance. AQP4-null mice are protected from cellular (cytotoxic) brain edema produced by water intoxication, brain ischemia, or meningitis. However, AQP4 deletion aggravates vasogenic (fluid leak) brain edema produced by tumor, cortical freeze, intraparenchymal fluid infusion, or brain abscess. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 deletion also worsens obstructive hydrocephalus. Recently, AQP4 was also found to play a major role in processes unrelated to brain edema, including astrocyte migration and neuronal excitability. These findings suggest that modulation of AQP4 expression or function may be beneficial in several cerebral disorders, including hyponatremic brain edema, hydrocephalus, stroke, tumor, infection, epilepsy, and traumatic brain injury. PMID- 17347839 TI - Laparoscopically assisted transhiatal esophagectomy with esophagogastroplasty for post-corrosive esophageal stricture treatment in children. AB - A tight post-corrosive esophageal stricture in a child poses significant surgical challenges. Many studies have described minimally invasive esophagectomy in adults, but very few reports have described this technique in children. Minimally invasive esophagectomy represents a new alternative to conventional open esophagectomy. This retrospective study evaluated the safety and efficacy of laparoscopically assisted transhiatal esophagectomy and gastric transposition for post-corrosive esophageal stricture treatment. Twenty-seven children with post corrosive esophageal stricture were subjected to this technique. Their ages ranged from 3 to 13.5 years (mean 5.6 years). Fourteen were females and thirteen were males. None of the procedures needed to be converted to an open approach, and there were neither intra-operative complications nor increased blood loss. Left-sided pneumothorax occurred in one case only (3.7%). The mean operating time was 160 min (range 120-180). Three patients were admitted postoperatively to intensive care unit for a period of 48 h for assisted ventilation. Mean hospital stay was 4 days (range 3-7 days). Anastomotic leakage occurred in three patients (11.1%), while anastomotic stricture occurred in four patients (14.8%). About 93.5% of our cases have achieved excellent results. Post-operative nutritional status was satisfactory and accepted. Laparoscopically assisted transhiatal esophagectomy and gastric transposition for post-corrosive esophageal stricture treatment in children is safe, visible, effective, and an accepted operative technique. The cosmetic result is excellent. PMID- 17347840 TI - Cardiac rhabdomyoma as an unusual mediastinal mass in a newborn. AB - A newborn case with cardiac rhabdomyoma is presented to discuss the differential diagnosis of mediastinal tumors around the heart in children. The diagnosis of rhabdomyoma can be suggested by modern visualization methods such as computerized tomography, magnetic resonance imaging and echocardiography. However, surgery is clearly indicated in cases with obstruction of flow tracts, valvular dysfunction and dysrhythmia, and in cases with indefinite diagnosis, or in the absence of association with tuberous sclerosis. Cardiac rhabdomyoma should be included in the differential diagnosis of masses located adjacent to the heart in infants. PMID- 17347841 TI - Optimising femoral component rotation using Equiflex instrumentation: a clinical review. AB - Although there is agreement that flexion and extension spaces should be symmetrical and that rotation of the femoral component impacts outcome in a knee replacement, there is dispute over what is the 'correct' rotation and how best to achieve it (Akagi et al., Clin Orthop Relat Res 366:155-163, 1999; Anouchi et al., Clin Orthop Relat Res 287:170-177, 1993; Barrack et al., Clin Orthop Relat Res 392:46-55, 2001; Berger et al., Clin Orthop Relat Res 356:144-153, 1998; Jenny and Boeri, Acta Orthop Scand 75(1):74-77, 2004; Poilvache et al., Clin Orthop Relat Res 331:35-46, 1996; Siston et al., J Bone Joint Surg Am 87(10):2276 2280, 2005). Insall and Scuderi recommended placing a tensor in flexion and rotating the femoral cutting block so that its posterior edge is parallel to the cut tibia (Insall, Surgery of the knee, vol 2, 2nd edn., Churchill Livingstone, New York, 1993; Scuderi and Insall, Orthop Clin N Am 20:71-78, 1989). We feel Equiflex instrumentation will reliably achieve Insall and Scuderi's recommendation. To evaluate early results and lateral retinacular release rates using Equiflex instrumentation for TKR, we evaluated 209 consecutive knees (31 valgus, 178 varus) using this technique from 4 April 2005 until 19 September 2006. Pre and postop American Knee Society and Oxford scores, deformity, ROM, lateral retinacular release rates and complications were recorded. We could correct alignment and achieve our technical goals in 99% of cases. A lateral retinacular release was required in only five knees (2.4%). The complications are comparable to published data. The Equiflex instrumentation does help in equalising flexion-extension gaps, improves patellar tracking and reduces the incidence of lateral retinacular release. PMID- 17347842 TI - A new material for prevention of peritendinous fibrotic adhesions after tendon repair: oxidised regenerated cellulose (Interceed), an absorbable adhesion barrier. AB - In this experimental study, we aimed to examine the ability of absorbable oxidised regenerated cellulose (Interceed, TC-7, Johnson & Johnson, USA) to inhibit the formation of peritendinous fibrotic adhesions after tendon repair in rats. Both Achilles tendons of 23 female Wistar-Albino rats weighing between 350 and 450 grams were cut and repaired. On the right side, Interceed absorbable adhesion barriers were wrapped around the repaired tendon (group I). On the left, the same procedures were applied except for the Interceed wrapping and these were grouped as control (group II). Animals were sacrificed at postoperative day 28 and macroscopic and histological examination was performed. All the animals survived and no tendon rupture was observed. No wound dehiscence, wound infection or exposure of repaired tendons occurred. Macroscopically, there were three (13.1%) tendons without adhesion formation and 20 (86.9%) tendons with inferior adhesion formation in group I; on the other hand, there were 16 tendons (69.5%) with medium grade adhesion formation and seven tendons (30.5%) with severe peritendinous adhesion formation in group II (control group) (p<0.05). Histologically, adhesion formation was absent in 11 tendons (47.8%) and slight in 12 tendons (52.2%) in group I; while in group II, it was slight in two (8.6%), moderate in 15 (65.2%) and severe in six tendons (26.2%) (p<0.05). Sixteen (69.5%) of 23 tendons in group I and 11 (47.8%) of 23 tendons in group II showed no inflammatory reaction (p<0.05). Nineteen (82.6%) tendons in group I and only one tendon in group II showed excellent to good tendon healing (p=0.00). According to our results, we feel that Interceed may have an intraoperative role to play in the reduction of adhesions after surgical tendon repair. This study suggests that absorbable oxidised regenerated cellulose merits further evaluation as a potential treatment to inhibit the formation of peritendinous adhesions. Rigorous and extensive controlled trials should be undertaken on patients undergoing tendon repair with or without this barrier. PMID- 17347843 TI - Young survivors of malignant bone tumours in the extremities: a comparative study of quality of life, fatigue and mental distress. AB - PURPOSE: The purpose of the study was to compare the quality of life (QoL), fatigue and mental distress in survivors of malignant extremity bone tumours (EBT survivors) with age and gender-matched survivors of Hodgkin's disease (HD survivors) and testicular cancer (TC survivors) as well as normative samples from the general population. PATIENTS AND METHODS: Five years or more after end of treatment, 75 EBT survivors were mailed a questionnaire containing Short Form-36 (SF-36), the Hospital Anxiety and Depression Scale, the Fatigue Questionnaire and questions about demography. Fifty-eight EBT survivors responded. TC survivors, HD survivors and normative samples (NORMs) had earlier on filled in the same questionnaire. For EBT survivors, gender and age-matched controls were randomly selected among TC survivors, HD survivors and NORMs. RESULTS: No significant differences in the fatigue or mental distress scores were observed between the survivor groups. The EBT survivors had significantly higher fatigue scores and lower depression scores than NORMs and significantly lower scores on all physical dimensions of QoL than TC survivors, HD survivors and NORMs. In multivariate analysis, a low level of education and lack of employment were significantly associated with caseness of mental distress. Older age at survey, female gender, being an EBT survivor and lack of employment were associated with caseness on the SF-36 Physical Component Summary Scale. CONCLUSION: At long-term follow-up, EBT survivors did not show impaired mental health or fatigue at the group level, although their post-treatment status was characterised by reduced QoL dimensions on physical function compared to TC survivors, HD survivors and NORMs. PMID- 17347844 TI - Systematic review of economic evaluations and cost analyses of guideline implementation strategies. AB - To appraise the quality of economic studies undertaken as part of evaluations of guideline implementation strategies, we conducted a systematic review of such studies published between 1966 and 1998. Studies were assessed against BMJ economic evaluations guidelines for each stage (guideline development, implementation and treatment). Of 235 studies identified, 63 reported some information on cost. Only 3 studies provided evidence that their guideline was effective and efficient, 38 reported treatment costs only, 12 implementation and treatment costs, 11 implementation costs alone, and 2 guideline development, implementation and treatment costs. No study gave reasonably complete information on costs. Thus, very few satisfactory economic evaluations of guideline implementation strategies have been performed. Current evaluations have numerous methodological defects and rarely consider all relevant costs and benefits. Future evaluations should focus on evaluating the implementation of evidence based guidelines. PMID- 17347845 TI - The cost-utility of magnetic resonance imaging for breast cancer in BRCA1 mutation carriers aged 30-49. AB - Recent evidence has investigated the cost-effectiveness of magnetic resonance imaging (MRI) in younger women with a BRCA1 mutation. However, this evidence has not been contrasted with existing cost-effectiveness standards to determine whether screening is appropriate, given limited societal resources. We constructed a Markov model investigating surveillance tools (mammography, MRI, both in parallel) under a National Health Service (NHS) perspective. The key benefit of MRI is that increased sensitivity leads to early detection, and improved prognosis. For a 30- to 39-year-old cohort, the cost per quality adjusted life year (QALY) of mammography relative to no screening was 5,200 pounds. The addition of MRI to this costs 13,486 pounds per QALY. For a 40- to 49 year-old cohort, the corresponding values were 2,913 pounds and 7,781 pounds. Probabilistic sensitivity analysis supported the cost-effectiveness of the parallel approach of mammography and MRI. It is necessary to extend this analysis beyond BRCA1 carriers within this age group, and also to other age groups. PMID- 17347846 TI - The incidence and cost of cardiac surgery adverse events in Australian (Victorian) hospitals 2003-2004. AB - The aim of this study was to estimate the incidence of adverse events in acute surgical admissions for cardiac disease in admitted episodes in the year 2003 2004 and to estimate the cost of these complications to the Victorian health system. Cardiac surgery adverse events are among the most frequent and significant contributors to the morbidity, mortality and cost associated with hospitalisation. Patient-level costing data set for major Victorian public hospitals in 2003-2004 was analysed for adverse events using C-prefixed markers, denoting complications that arose during the course of hospital treatment for cardiac surgery diagnosis related groups (DRGs). The cost of adverse events was estimated by linear regression modelling, adjusted for age and co-morbidity. A total of 16,766 multi-day cardiac disease cases were identified, of whom 6,181 (36.85%) had at least one adverse event. Patients with adverse events stayed approximately 7 days longer and had four times the case fatality rate than those without. After adjustment for age and co-morbidity, the presence of an adverse event adds AUS$5,751. The sum of the total cost of adverse events for each DRG was AUS$42.855 million, representing 21.6% of total expenditure on cardiac surgery and adding 27.5% in broad terms to the cardiac surgery budget. PMID- 17347847 TI - Lymphoma-associated hemophagocytic syndrome: clinical features and treatment outcome. AB - The clinical features and prognostic factor of lymphoma-associated hemophagocytic syndrome (LAHS), diagnosed according to World Health Organization classification, were investigated by reviewing the clinical records of 29 patients between September 1994 and September 2006. Compared with patients with T or natural killer (NK)/T cell LAHS, patients with B cell LAHS were older (p = 0.022), were less likely to exhibit disseminated intravascular coagulation (DIC; p = 0.011), and had less direct involvement of bone marrow (p = 0.03). Clinical response was achieved in 15 (65.2%) and complete remission (CR) was achieved in 4 (17%) of 23 patients who received chemotherapy. Four patients received high-dose chemotherapy and autologous stem cell transplantation (A-SCT), and three of these four patients showed CR. The median survival was 36 days (95%CI, 20.2-51.8). Univariate analysis showed that poor performance status (p = 0.028), T or NK/T cell lymphoma (p = 0.016), presence of jaundice (p = 0.063), the presence of DIC (p = 0.002), and poor clinical response to treatment (p < 0.001) predicted poor overall survival. These data suggest that the clinical features differ significantly between B cell LAHS and T or NK/T cell LAHS. Intensive treatment including high-dose chemotherapy and A-SCT should be investigated. PMID- 17347848 TI - Involvement of AMPA/kainate, NMDA, and mGlu5 receptors in the nucleus accumbens core in cue-induced reinstatement of cocaine seeking in rats. AB - RATIONALE: Nucleus accumbens glutamate transmission has been implicated in drug seeking behavior, but the involvement of glutamate receptor subtypes in drug seeking maintained by drug-associated cues has not been fully investigated. OBJECTIVE: This study examined the effects of alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA)/kainate, N-methyl-D-aspartate (NMDA) and mGlu5 receptor blockade in the nucleus accumbens core on cue-induced reinstatement of cocaine seeking. METHOD: Wistar rats were trained to self-administer cocaine and associate a compound stimulus (light and tone) with the drug under an FR4(FR5:S) second-order schedule of reinforcement. After extinction, during which neither cocaine nor the compound stimulus was available, responding was reinstated by contingent presentations of the compound stimulus. The effects of the intra accumbal AMPA/kainate receptor antagonist 6-cyano-7-nitro-quinoxaline-2, 3-dione (CNQX; 0, 0.01, and 0.03 microg/side), the NMDA antagonist D-2-amino-5 phosphonopentanoate (D-AP5; 0, 1, and 2 microg/side), and the mGluR5 antagonist 2 methyl-6-(phenylethynyl)-pyridine (MPEP; 0, 0.5, and 1 microg/side) on reinstatement were examined in a within-subjects design. RESULTS: CNQX and D-AP5 attenuated cue-induced reinstatement of cocaine seeking dose-dependently. MPEP, however, decreased cocaine seeking only relative to baseline because also the saline vehicle included in the within-subjects series of injections decreased responding, possibly reflecting conditioned anhedonic effects of MPEP. In additional experiments, none of the antagonists attenuated locomotor activity or responding for sucrose pellets. CONCLUSIONS: The results suggest that cue-induced reinstatement of cocaine seeking after a period of withdrawal from cocaine is sensitive to AMPA/kainate and NMDA receptor antagonism in the nucleus accumbens core and give further evidence for the role of the accumbal glutamate transmission in modulation of drug-seeking behavior. PMID- 17347849 TI - Dickkopf-3 is expressed in a subset of adult human pancreatic beta cells. AB - The Dickkopf (Dkk) gene family of secretory modulators of canonical Wnt/beta catenin signals is involved in the control of stem cell proliferation, homeostasis and differentiation. Bioinformatic data on dkk-1/3 gene expression, indicating high expression levels in the human pancreas, led us to analyze these two proteins in adult human pancreatic tissue. Dkk-1/3 mRNA levels and protein distribution were analyzed in isolated human islets vs. the exocrine/ductal pancreatic cells and in paraffin sections of adult human pancreata. Using real time PCR only lowest amounts of dkk-1 mRNA were detectable in the endocrine fractions. Immunohistochemistry did not reveal any Dkk-1 protein in adult human pancreatic tissue. Interestingly, Dkk-3 mRNA and protein were clearly present in adult human pancreatic islets. Messenger RNA levels for Dkk-3 were significantly higher in isolated islets as compared to the exocrine/ductal fraction. Co staining with an antibody against insulin identified the beta cells of the pancreas as the Dkk-3-positive cells. Notably, only a subset of beta cells contained Dkk-3. As shown by western blot analysis Dkk-3 seems to be proteolytically processed in beta cells. To our knowledge, this is the first study describing a molecule with which the pool of pancreatic beta cells can be further subdivided. Future studies will show whether this sub-classification of beta cells translates into functional differences. PMID- 17347850 TI - Identification of differentially expressed genes in female Culex pipiens pallens. AB - Culex pipiens pallens is the mosquito vector of a number of human pathogens such as Wuchereria bancrofti, Brugia malayi, and epidemic encephalitis B virus. Female C. pipiens pallens play an important role in transmitting pathogens by sucking blood, which is essential for reproduction. In the present study, a subtractive cDNA library for female C. pipiens pallens was constructed by the suppression subtractive hybridization (SSH) technique and then 100 clones from the female SSH library were sequenced and analyzed. Female-differentially expressed genes in C. pipiens pallens were screened using semiquantitative RT-PCR. The full-length cDNA of an EST sequence (fs68) that was specifically expressed in female C. pipiens pallens was characterized by 3' and 5' rapid amplification of cDNA ends (RACE). The characteristics of the female-specific gene were further analyzed using bioinformatics and Northern blot. It was shown that the female-specific gene was a previously uncharacterized gene and may encode a salivary peptide. This putative salivary peptide could be a very important molecule in the blood feeding of female C. pipiens pallens. PMID- 17347851 TI - Down regulation of small intestinal ion transport in PDZK1- (CAP70/NHERF3) deficient mice. AB - The PDZ-binding protein PDZK1 (CAP70/PDZ-dc-1/NHERF3) in vitro binds to cystic fibrosis transmembrane conductance regulator (CFTR), the anion exchangers SLC26A3 and SLC26A6 and the Na(+)/H(+) exchanger NHE3, all of which are major transport proteins for intestinal anion secretion and salt absorption. This study was undertaken to search for a role of PDZK1 in regulating electrolyte transport in native murine small intestine. Short circuit current (I (SC)) and HCO-(3) secretory rate (J(HCO-)(3)) were measured to assess electrogenic anion secretion; (22)Na(+) fluxes to assess sodium absorption in isolated small intestine. NHE3, CFTR, as well as NHERF1, NHERF2, and PDZK1 messenger RNA (mRNA) expression levels, and NHE3 total enterocyte and brush border membrane (BBM) protein abundance were determined by quantitative polymerase chain reaction (PCR) and Western analysis. NHE3 localization was performed by immunohistochemistry. In pdzk1 -/- jejunal mucosa, basal net Na(+) absorption as well as the inhibition of Na(+) absorption by forskolin was significantly reduced. In pdzk1 -/- duodenal mucosa, identical basal I (SC) and (J(HCO-)(3)) but a significant, yet mild, reduction of forskolin-stimulated Delta(J(HCO-)(3)) and DeltaI (SC) was observed compared to +/+ tissue. Tissue conductance, morphological features, and the DeltaI (SC) and increase in (22)Na(+) absorption in response to luminal glucose was identical in pdzk1 +/+ and -/- small intestine, ruling out a general absorptive defect. While CFTR mRNA expression levels were unchanged, NHE3 mRNA expression levels were significantly increased in small intestinal mucosa of pdzk1 -/- mice. Total enterocyte and BBM abundance was not significantly different, suggesting an increased NHE3 turnover, possibly due to reduced NHE3 membrane retention time. Lack of the PDZ-adapter protein PDZK1 in murine small intestine causes a mild reduction in maximal CFTR activation, but a severe defect in electroneutral Na(+) absorption. PMID- 17347854 TI - [European Pneumology--a special challenge for Germany and Austria]. PMID- 17347852 TI - Biodiversity of voltage sensor domain proteins. AB - The six-transmembrane type voltage-gated ion channels play an essential role in neuronal excitability, muscle contraction, and secretion. The voltage sensor domain (VSD) is the key element of voltage-gated ion channels for sensing transmembrane potential, and has been studied at the levels of both biophysics and protein structure. Two recently identified proteins containing VSD without a pore domain showed unexpected biological roles: regulation of phosphatase activity and proton permeation. These proteins not only provide novel platforms to understand mechanisms of voltage sensing and ion permeation but also highlight previously unappreciated roles of membrane potential in non-neuronal cells. PMID- 17347856 TI - An extreme case of neurofibromatosis type 1. PMID- 17347855 TI - Molecular epidemiology of tuberculosis: toy or tool? A review of the literature and examples from Central Europe. AB - Genotyping has become an indispensable tool in medical microbiology and epidemiology. One of the first targets has been Mycobacterium tuberculosis. Over the past 15 years approximately 900 pertinent publications have substantiated the value of the genotyping approach for tuberculosis control. New insights into the understanding of the natural history of tuberculosis, especially regarding the frequencies of reactivation, reinfection or multiple infection entailed adaptations of pathophysiological concepts. However, assessment of recent transmission, outbreak analysis, and detection of laboratory contamination still form the genuine scope of genotyping. Detection of unsuspected clusters of cases can provide clues to search for further, undetected cases. Uncovering false positive cultures spares the risks and costs of unnecessary treatment and may reveal systematic laboratory weaknesses. Several European countries already profit from nationwide prospective fingerprinting. After providing genotyping results to public health officials, these were able to document epidemiological links for substantially more tuberculosis patients. On a global scale, strain families and particular strains have been identified, characterised and traced in their spread. The importation of Beijing-genotype multidrug-resistant M. tuberculosis into Central European countries will be described here as an example. The goal for further developments is the ability to compare isolates for epidemiological purposes in a single step that also comprises species determination, drug resistance testing and detection of pathogenicity factors. PMID- 17347857 TI - [Cost of disorders of the brain in Austria in the year 2004]. AB - OBJECTIVES: The costs of twelve selected neurological, neuro-surgical and psychiatric disorders in Austria in the year 2004 will be presented. The present paper is part of the "Cost of Disorders of the Brain in Europe" study. METHODS: The data for the present calculations are based on systematic reviews of epidemiological and health-economic studies. For all European countries identical methods were applied. All economic data were transformed to Euros for Austria in the year 2004 ("Purchasing Power Parity adjusted"). RESULTS: The highest costs per case per disorder were caused by brain tumors (49,800 Euro) and multiple sclerosis (30,500 Euro). One-year-prevalence estimates (Austrian population 8.1 million) were highest for anxiety disorders (848,000 cases), followed by migraine (537,000 cases) and affective disorders (479,000 cases). The total costs (i.e. for all cases of a specific disorder in Austria) were highest for affective disorders and addiction (alcohol and illegal drugs). The total cost of all included disorders (addiction, affective disorders, anxiety disorders, brain tumours, dementia, epilepsy, migraine, multiple sclerosis, Parkinson's disease, psychotic disorders, stroke and brain trauma) was estimated at 8.8 billion Euros for Austria in the year 2004. Direct health care cost amounted to Euros 3.2 billion (37% of total cost), direct non-medical cost totalled Euros 1.5 billion (17%), and indirect cost Euros 4.1 billion (47%). DISCUSSION: Even when considering that such estimates based on international studies have methodological limitations, the total cost of the twelve included disorders is considerable. The total cost of these twelve disorders constitutes 4% of the gross national product of Austria. Taken together, these disorders cost each Austrian citizen Euros 1 090 per year. PMID- 17347858 TI - Plasma ghrelin response to an oral glucose load in growth hormone-deficient adults treated with growth hormone. AB - BACKGROUND: Little is known about the pathophysiology of ghrelin secretion in growth hormone-deficient adults treated with growth hormone, and the relationship between plasma ghrelin and hyperinsulinemia induced by an oral glucose load has not been investigated in these patients. OBJECTIVE: In the present study we examined the relationship between plasma ghrelin, insulin, C-peptide and leptin after an oral glucose load in growth hormone-deficient adults receiving treatment with growth hormone. METHODS: Plasma ghrelin, leptin, insulin, C-peptide and blood glucose were measured before and then at 30, 60, 90 and 120 min after the ingestion of glucose (75 g orally) in 20 growth hormone-deficient adults (12 women and 8 men), who had been treated with growth hormone for 7.2 +/- 1.3 years (mean +/- SE). Plasma ghrelin was also determined before and after the glucose load in 10 age-and weight-matched healthy persons (5 women and 5 men). RESULTS: The oral glucose load induced a similar percent suppression of plasma ghrelin in the growth hormone-deficient patients and in the healthy persons. In both groups plasma ghrelin decreased significantly 30 min after the glucose load and remained suppressed throughout the test period. In the patients plasma insulin (baseline, 15.9 +/- 3.9 microIU/ml) and C-peptide (baseline, 2.5 +/- 0.3 ng/ml) showed opposite changes with peak responses at 30 min (insulin, 109.5 +/- 15.6 microIU/ml) or 60 min (C-peptide, 10.3 +/- 1.1 ng/ml). In these patients, post glucose, but not baseline plasma ghrelin levels correlated negatively with plasma insulin, C-peptide and blood glucose levels, whereas baseline plasma ghrelin correlated inversely with baseline plasma leptin. CONCLUSIONS: The similar suppression of plasma ghrelin in growth hormone-deficient patients treated with growth hormone and in healthy persons after an oral glucose load argues against disturbed regulation of ghrelin secretion in these patients. The correlations between post-glucose plasma ghrelin, insulin and blood glucose support the existence of a previously proposed link between hyperinsulinemia (or increased blood glucose) and suppression of ghrelin levels. PMID- 17347859 TI - Another 'soberade' on the market: does Outox keep its promise? AB - OBJECTIVE: Several products are being widely promoted for reduction of the concentration of alcohol in the human body. One of these preparations, the fructose soft drink Outox, claims to noticeably increase the alcohol elimination rate (beta 60). Theories to explain this 'fructose effect' are based on the assumption that NAD+, the coenzyme for alcohol dehydrogenase, is regenerated faster in the presence of fructose. METHOD: A randomized double-blind, placebo controlled cross-over study was performed with 30 volunteers in two drinking sessions each. Under strictly identical conditions, the same amount of alcohol was consumed, followed by the consumption of either 250 ml Outox or 250 ml placebo. Periodical measurements of blood (BAC), breath (BrAC) and urine alcohol concentration (UAC) were performed. RESULTS: Analyses revealed a significant difference (P<0.0001) between the mean alcohol levels of the Outox and the placebo drinking sessions. The overall mean BAC difference was 0.077 g/l (BAC 0.748 g/l without vs 0.671 g/l with Outox), equivalent to 10.3%. The mean BrAC difference was 0.045 mg/l (BrAC 0.314 mg/l without vs 0.269 mg/l with Outox), equivalent to 14.3%. Differences were lower for women than for men. A significant difference between the alcohol elimination rates (beta 60) was not found. CONCLUSIONS: The results show that the soft drink Outox may decrease the alcohol concentration by about 10%. However, BAC and BrAC differences are rather a consequence of slower gastric absorption of alcohol, because Outox does not increase the alcohol elimination rate. Our study demonstrates that the claim of Outox or other fructose drinks to work as a 'soberade' cannot be proven from a scientific point of view. It should be the task of physicians to warn potential consumers, especially in connection with drinking and driving. PMID- 17347860 TI - Competency and educational needs in palliative care. AB - PURPOSE: To explore general practitioners' (GPs') and nurses' self assessment of professional education, competency and educational needs in palliative care. METHODS: All 897 registered GPs and all 933 registered home care nurses in the Province of Styria/Austria were sent postal questionnaires to evaluate their professional training in (i) pain control and symptom management, (ii) handling psychosocial needs and (iii) ability to cope with work-related distress. RESULTS: 61.8% of 546 evaluable respondents felt not at all or not sufficiently prepared for palliative care by their professional education (GPs: 70%, nurses: 50.4%). GPs rated the competency of their professional guild significantly higher and their educational needs significantly lower than nurses (p<0.01). Both, GPs and nurses emphasised a great need for education in the area of neuropsychiatric symptom management. CONCLUSION: Our results provide a detailed analysis of needs and may help to target goals for training seminars in palliative care. PMID- 17347861 TI - Learning by doing: a novel approach to improving general practitioners' diagnostic skills for common mental disorders. AB - INTRODUCTION: Two strategies have been proposed to increase the rather low recognition rate of common mental disorders in primary care: (1) the use of screening instruments and (2) extensive psychiatric training for general practitioners. We have chosen a "middle-of-the-road" approach to teach general practitioners by means of a time-saving psychiatric training programme how to make their own psychiatric diagnoses. This pilot study aimed at assessing the acceptance of this programme, its impact on general practitioners' knowledge of 12 ICD-10 disorders - depressive, anxiety and alcohol-related disorders - and the short-term persistence of the knowledge acquired. METHODS: The training programme consisted of two 3-hour sessions four weeks apart. An educational instrument, a short interview named TRIPS (Training for Interactive Psychiatric Screening), a shortened and adapted form of PRIME-MD, was used to train single-handed general practitioners in Vienna, Austria. TRIPS had to be used by the participants in daily practice in between sessions. Five weeks after the second training session a follow-up evaluation was held to assess the persistence of the knowledge acquired. The perceived usefulness of TRIPS was assessed by a short questionnaire. Knowledge was assessed by a separate 15-item questionnaire. RESULTS: Of the 31 participating general practitioners 26 attended all three sessions. There was a significant increase in the mean number of correctly answered questions between baseline (5.5 of 15) and session two (9.8; p<0.0001), and a further increase between the second and the follow-up session (11.3; p<0.05). Also, general practitioners rated TRIPS as a practical and useful tool for family practice and stated that its use met with patients' approval. CONCLUSION: The format chosen was successful in its intended educational endpoints. According to participants TRIPS is appropriate for the family practice situation and is accepted by patients. PMID- 17347862 TI - A comparison of two different treatments with navigated extracorporeal shock-wave therapy for calcifying tendinitis - a randomized controlled trial. AB - BACKGROUND: Extracorporeal shock-wave therapy is recommended for calcifying tendinitis, and navigated low-energy therapy has given better results than biofeedback localization. This investigation was planned to analyze whether the outcome of navigated low-energy shock-wave therapy can be improved by raising energy flux density to middle-energy levels. The clinical and radiological differences in outcome between three sessions of low-energy navigated shock-wave therapy and two sessions of middle-energy therapy were therefore compared. PATIENTS, MATERIALS AND METHODS: A prospective, randomized, observer-blind study was carried out in 50 patients whose mean age was 51 years. The population was randomized into two groups. Pain refractory to therapy was evident for more than six months in all patients. Radiographs and clinical examinations, including the Constant and Murley score, and the visual analog scale for pain assessment were performed before therapy and then after 12 weeks. Both groups of patients received navigated and X-ray-assisted, focused shock-wave treatment at weekly intervals. Group I underwent three sessions of constant low-energy treatment (0.08 mJ/mm(2); 1000 impulses) without local anesthesia; Group II received two middle-energy treatments (0.2 mJ/mm(2); 2000 impulses) with subacromial anesthesia. RESULTS: Forty-four patients (21 in Group I, 23 in Group II) completed the study protocol. Clinically, both groups improved significantly (P<0.0001) in the Constant and Murley score and the visual analog scale. The statistics within the groups were not significantly different. Overall, nine calcium deposits disappeared and 12 changed massively in shape and radiological density. CONCLUSIONS: Navigated shock-wave therapy significantly improves pain and shoulder function. Patients obtained nearly equal results after three low energy or two middle-energy sessions of shock-wave treatment. We therefore recommend two sessions of middle-energy shock-wave therapy, as performed in Group II, because of the time-saving factor. PMID- 17347863 TI - Hypocalcemic tetany in the newborn as a manifestation of unrecognized maternal primary hyperparathyroidism. AB - Primary hyperparathyroidism (PHP) during pregnancy is a very rare event that increases maternal and perinatal morbidity and mortality. We present a case in which hypocalcemic tetany of the neonatal infant - caused by transient hypoparathyroidism in the child - finally revealed asymptomatic maternal PHP. An apparently healthy 30-year-old woman had an uneventful pregnancy and delivery. On the 15th postpartal day, the newborn developed hypocalcemic tetany. After receiving supplementation of calcium and vitamin D, the child developed without further pathological findings. Laboratory and radiological studies in the mother led to a diagnosis of maternal PHP. An adenoma of the right lower parathyroid gland was subsequently removed. The search for the cause of hypocalcemia in a newborn should not focus on the patient alone. Examining the apparently healthy mother and approaching the case in a multidisciplinary fashion may benefit both the child and the mother. PMID- 17347864 TI - Dr. Franjo (Franz) Kresnik (1869-1943): a physician and a violin maker. AB - Dr. Franjo (Franz) Kresnik (born Wien 1869 - died Rijeka 1943) was an excellent physician and a Central European intellectual, a bohemian mind whose two loves in life made him very special. His passions were medicine and violin making. Most of his life was spent in Susak (now a part of Rijeka, Croatia), where he worked, played music and studied the art of making stringed instruments. He visited Cremona on several occasions and studied a number of violins, drawings and tools made and used by old masters. For his profound knowledge of Cremonese violin making the Italians dubbed him "Uomo che legge violini" (The Man Who Can Read Violins). In his workshop he made fifty-two violins, two violas, two cellos and a string quartet. Some of these instruments are still played in Europe and America. The remaining violins and possessions (tools, manuscripts, drawings, literature and countless diplomas and certificates) have been kept in a memorial room at the Maritime and History Museum of the Croatian Littoral in Rijeka. In addition, a street near the Faculty of Medicine in Rijeka is named after Franjo Kresnik. PMID- 17347865 TI - Suicide by shooting is correlated to rate of gun licenses in Austrian counties. PMID- 17347866 TI - Molecular cloning and comparison of avian preproghrelin genes. AB - We report cDNA sequences for the preproghrelin gene from goose, duck, and emu. This gene is involved in stimulating the release of growth hormone in mammals and may play a similar role in avian species. The complete coding sequence of avian preproghrelin encodes a 116 amino acid (aa) protein, which is organized into three parts: the N-terminal hydrophobic signal peptide, a 26 aa peptide for mature ghrelin, and a long C-terminal polypeptide. Domain/motif structures of preproghrelin protein are highly conserved among avian species. Although the avian and mammalian homologs are not highly similar for the whole 116 aa sequence, the identity of the highly conserved "active core" sequence and the n octanoyl modification of the serine 3 residue avian ghrelin protein with its mammalian homologs implies conserved function of ghrelin protein during evolution. Information provided in this study will be useful in further studies to determine the role the preproghrelin gene plays in the regulation of growth hormone release and body weight gain in avian species. PMID- 17347867 TI - Bioinformatic and image analyses of the cellular localization of the apoptotic proteins endonuclease G, AIF, and AMID during apoptosis in human cells. AB - We studied the cellular localization of the apoptotic proteins endonuclease G, AIF, and AMID in silico using three prediction tools and in living cells using both single-cell colocalization image analysis and nuclear translocation analysis. We confirmed the mitochondrial localization of endonuclease G and AIF by prediction analysis and by single-cell colocalization image analysis. We found the AMID protein to be cytoplasmic, most probably incorporated into the cytoplasmic side of the membranes of various organelles. The highest concentration of AMID was observed associated with the Golgi. Colocalization of AMID with lysosomes was also indirectly confirmed by analysis of AMID-rich vesicle velocity using manual tracking analysis. Bioinformatic analysis also detected nuclear localization signals in endonuclease G and AIF, but not in AMID. A novel analysis of time-lapse fluorescence image data during staurosporine induced apoptosis revealed nuclear translocation only for endonuclease G and AIF. PMID- 17347868 TI - Lysosomal and mitochondrial pathways in miltefosine-induced apoptosis in U937 cells. AB - Hexadecylphosphocholine (HePC) is an anticancer agent whose effect has been shown to involve apoptosis induction but the signaling pathways leading to apoptosis remain to be elucidated. We show here that HePC induces activation of caspase-9, 3, and -8 via the intrinsic pathway, release of cytochrome c, activation and relocation of Bax to the mitochondria as well as the cleavage of Bid. Moreover, a lysosomal pathway characterized by partial lysosomal rupture, cathepsin B activation and relocation from lysosomes to the cytosol, is involved in HePC induced apoptosis. A cathepsin B/L inhibitor partially suppresses caspase activation and apoptosis induction, indicating signaling between lysosomes and mitochondria. Conversely, the pancaspase inhibitor Q-VD-OPH inhibits lysosomal rupture, but only at early time points, suggesting that immediate lysosomal rupture involves caspases. Overexpression of Bcl-2, an anti-apoptotic protein known to prevent mitochondrial dysfunction, totally abrogates lysosomal destabilization and cell death. PMID- 17347869 TI - Successful ablation of atrioventricular node reentry tachycardia in a patient with crisscross heart and situs inversus levocardia. AB - Crisscross heart is a complex congenital anomaly that is rarely seen in the absence of important associated structural defects. We describe a 41-year-old woman with recurrent dizziness and tachycardia but no previous cardiovascular symptoms. Narrow-QRS tachycardia was detected, and magnetic resonance imaging showed situs inversus levocardia with a circulatory pattern typical of crisscross heart. Electrophysiologic study revealed atypical atrioventricular (AV) node reentry tachycardia of the "fast-slow" type. Despite the unusual anatomy, we successfully modified the AV node physiology by ablating the "slow AV node inputs" with the guidance of a multielectrode basket catheter in the anatomic right atrium. PMID- 17347870 TI - Childlessness, psychological well-being, and life satisfaction among the elderly in China. AB - This paper examines the effects of childlessness on the well-being of persons aged 65 and above in China. It is based on an application of ordered-logit regression in the analysis of the data from the 2002 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted in 22 provinces of China (N = 13,447). It compares parents with the childless elderly, focusing on three dimensions of psychological well-being, namely feelings of anxiety, loneliness, and uselessness, and on life satisfaction. The findings include the following. First, with control of social demographic variables of age, gender and education, childlessness is significantly associated with life satisfaction, feeling of anxiety and loneliness, but not feeling of uselessness. The childless elderly are less satisfied with their lives and feel more anxious and lonely than do parents, but they do not necessarily feel significantly more useless. Second, when controlled with social-demographic variables and additional socioeconomic variables of residence, living arrangement, availability of pension and medical services, childlessness is no longer significantly related to anxiety and loneliness, and it is related at only a marginally-significant level to life satisfaction. Third, individual education, place of residence, living arrangements, economic security and access to medical services are consistently related to life satisfaction and psychological well-being among the elderly. We conclude that providing social investments in education in early life and economic security and medical insurance in later life for both the childless and parents are crucial for improving individual psychological well-being and life satisfaction for the elderly. PMID- 17347871 TI - Human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry. AB - Ixabepilone (BMS-247550) is a semi-synthetic, microtubule stabilizing epothilone B analogue which is more potent than taxanes and has displayed activity in taxane resistant patients. The human plasma pharmacokinetics of ixabepilone have been described. However, the excretory pathways and contribution of metabolism to ixabepilone elimination have not been determined. To investigate the elimination pathways of ixabepilone we initiated a mass balance study in cancer patients. Due to autoradiolysis, ixabepilone proved to be very unstable when labeled with conventional [14C]-levels (100 microCi in a typical human radio-tracer study). This necessitated the use of much lower levels of [14C]-labeling and an ultra sensitive detection method, Accelerator Mass Spectrometry (AMS). Eight patients with advanced cancer (3 males, 5 females; median age 54.5 y; performance status 0 2) received an intravenous dose of 70 mg, 80 nCi of [14C]ixabepilone over 3 h. Plasma, urine and faeces were collected up to 7 days after administration and total radioactivity (TRA) was determined using AMS. Ixabepilone in plasma and urine was quantitated using a validated LC-MS/MS method. Mean recovery of ixabepilone-derived radioactivity was 77.3% of dose. Fecal excretion was 52.2% and urinary excretion was 25.1%. Only a minor part of TRA is accounted for by unchanged ixabepilone in both plasma and urine, which indicates that metabolism is a major elimination mechanism for this drug. Future studies should focus on structural elucidation of ixabepilone metabolites and characterization of their activities. PMID- 17347872 TI - Antitumor activity of enzastaurin (LY317615.HCl) against human cancer cell lines and freshly explanted tumors investigated in in-vitro [corrected] soft-agar cloning experiments. AB - Enzastaurin (LY317615.HCl) is an antiproliferative agent targeted specifically against PKC-beta. We have investigated the antitumoral effects of Enzastaurin against human cancer cell lines and freshly explanted human tumor tissue. Ten human cancer cell lines (NSCLC, colon, and thyroid) and human tumor specimens from 72 patients were used for in vitro studies in a cloning assay (HTCA). Cell lines and primary tumor cells were exposed to Enzastaurin for either 1 h or 7 days, or for 1 h or 21 days. At clinically achievable concentrations of Enzastaurin, inhibition of cell growth was observed for lung, colorectal, and thyroid cancer cell lines in a concentration dependent manner. Patient specimens exposed 1 h or 21 days to 1,400 nM Enzastaurin demonstrated inhibition rates of 24 and 32%, respectively. Marked inhibitory effects were observed in breast, thyroid, head/neck, non-small cell lung cancer, pancreatic cancer, and melanoma. In addition to its established antiangiogenic effects, Enzastaurin has direct antitumor activity against established human cancer cell lines and primary tumor specimens. This warrants further clinical development in tumors which have been identified to be potentially sensitive to Enzastaurin. PMID- 17347873 TI - TSH-secreting pituitary adenomas: follow-up of 11 cases and review of the literature. AB - Thyrotropin (TSH)-secreting pituitary adenomas account for less than 1% of all pituitary tumors. In the last two decades, their clinical management has changed markedly due to technological advances that made earlier diagnosis possible and the introduction of somatostatin analog therapy. We retrieved the data of 11 patients in Israel diagnosed with TSH-secreting pituitary tumors since 1989. There were six men and five women of mean age 44.8 +/- 19.5 years (range 18-80 years). All had elevated thyroxine and triidothyronine levels with nonsuppressed TSH and imaging evidence of a pituitary tumor. In three patients the tumor co secreted growth hormone. Ten patients had macroadenomas (> or =10 mm) and one patient had a microadenoma (<10 mm). Nine patients underwent surgery, and all had postoperative evidence of residual tumor. Ten patients received long-term somatostatin analog therapy (9 postoperatively, 1 primarily), which controlled the hyperthyroidism in all of them. In addition, three patients showed tumor shrinkage and seven, stabilization of tumor growth.In conclusion, in patients with TSH-secreting pituitary adenomas, somatostatin therapy appears to be highly effective in treating hyperthyroidism and in halting tumor growth or promoting tumor shrinkage. PMID- 17347874 TI - The metabolic changes caused by dexamethasone in the adjuvant-induced arthritic rat. AB - The action of orally administered dexamethasone (0.2 mg kg(-1) day(-1)) on metabolic parameters of adjuvant-induced arthritic rats was investigated. The body weight gain and the progression of the disease were also monitored. Dexamethasone was very effective in suppressing the Freund's adjuvant-induced paw edema and the appearance of secondary lesions. In contrast, the body weight loss of dexamethasone-treated arthritic rats was more accentuated than that of untreated arthritic or normal rats treated with dexamethasone, indicating additive harmful effects. The perfused livers from dexamethasone-treated arthritic rats presented high content of glycogen in both fed and fasted conditions, as indicated by the higher rates of glucose release in the absence of exogenous substrate. The metabolization of exogenous L: -alanine was increased in livers from dexamethasone-treated arthritic rats in comparison with untreated arthritic rats, but there was a diversion of carbon flux from glucose to L: lactate and pyruvate. Plasmatic levels of insulin and glucose were significantly higher in arthritic rats following dexamethasone administration. Most of these changes were also found in livers from normal rats treated with dexamethasone. The observed changes in L: -alanine metabolism and glycogen synthesis indicate that insulin was the dominant hormone in the regulation of the liver glucose metabolism even in the fasting condition. The prevalence of the metabolic effects of dexamethasone over those ones induced by the arthritis disease suggests that dexamethasone administration was able to suppress the mechanisms implicated in the development of the arthritis-induced hepatic metabolic changes. It seems thus plausible to assume that those factors responsible for the inflammatory responses in the paws and for the secondary lesions may be also implicated in the liver metabolic changes, but not in the body weight loss of arthritic rats. PMID- 17347876 TI - Where young MSM meet their first sexual partner: the role of the Internet. AB - The objective was to examine how many young men who have sex with men (MSM) meet their first sexual partner through the Internet and whether this has increased over time. In 2003, 2505 MSM surveyed on UK Internet sites completed a self administered questionnaire. Data were analysed for 810 MSM who were under 30 years old at the time of the survey and who first had sex with another man between 1993-2002. During this period there was a significant increase in the percentage of MSM who met their first male sexual partner through the Internet (2.6-61.0%). There was a corresponding decrease in the percentage who met their first sexual partner at a gay venue (34.2-16.9%), school (23.7-1.3%), a public sex environment, through small ads or telephone chatlines (10.5-1.3%). An increasing number of young MSM appear to meet their first sexual partner through the Internet. Online sexual health interventions should be developed targeting men early in their sexual careers. PMID- 17347875 TI - Depressive experiences in inpatients with borderline personality disorder. AB - We investigate the quality of dependent and self-critical depressive experiences in a hospitalized sample of depressed (n = 17), depressed borderline (n = 29), and borderline non-depressed inpatients (n = 10). Subjects were administered structured diagnostic interviews for axis I and axis II along with the Symptom Checklist-90-Revised Depression Scale (SCL-90-R-DS) and the Depressive Experiences Questionnaire (DEQ). As predicted, there were no differences between the three groups in overall level of impairment or severity of depression. Phenomenologically, however, depressive experiences were quite different. Subjects with borderline personality disorder, with and without a diagnosed depressive disorder, scored higher than subjects with depression only on the measure of anaclitic neediness. Further analyses revealed that anaclitic neediness was significantly associated with interpersonal distress, self destructive behaviors, and impulsivity. Findings suggest the importance of considering phenomenological aspects of depression in borderline pathology. PMID- 17347877 TI - HIV voluntary counseling and testing among injection drug users in south China: a study of a non-government organization based program. AB - HIV voluntary counseling and testing (VCT) programs are usually delivered by government health agencies in China. This study examined the feasibility of using a Chinese non-government organization (NGO) to deliver a VCT program to injection drug users (IDUs) in a southern Chinese city. The process data indicated the program successfully recruited and served 226 male and female IDUs in 4 months. The HIV prevalence rate of the study population was 57.5% by rapid HIV testing with a secondary rapid test to confirm. Quantitative and qualitative evaluations indicated that the VCT program was implemented appropriately and participants' HIV knowledge and safe drug and sex practices were significantly improved after participation in the VCT program. This study demonstrates the feasibility of a Chinese NGO to provide VCT for IDUs and documents the processes and outcomes of the program. There remains a great need to find additional sources to provide VCT and other HIV prevention services to IDUs and other high-risk populations in China. Chinese NGOs have the potential to fill this need. PMID- 17347878 TI - Acquiring explicit grammatical knowledge using the Spanish verbs ser and estar as examples. AB - The role of explicit and implicit acquisition of grammatical rules in second language learning was examined by assessing high school students performance after several years of study on the correct use of the Spanish verbs ser and estar. These two verbs are essentially equivalent in use to the English verb "to be," but there is a complex set of statements that specifies when each is to be used. A 100-item two-choice test in which students from several different high schools receiving instruction in the explicit principles of these two Spanish verbs or receiving immersion training in which no instruction in their grammatical principles was given were examined for the following five factors: (a) general achievement level, (b) comparison of grade level achievement, (c) time allotted to complete the 100-item test, (d) grammatical instruction prior to taking the 100-item test, and (e) comparison of instructional methodology. The results indicated that students receiving explicit instruction in the rules of ser and estar beyond the first year of study achieved slightly higher scores, but that the level of achievement was considered to be poor. Differences between groups for the remaining factors were not significant. It was concluded that successful application of explicitly learned grammatical rules, such as the rules for ser and estar, may not be achievable in the time frame of a two-year high school foreign language course. Considerations regarding implicit and explicit acquisition of grammatical rules in second language learning were presented. PMID- 17347879 TI - Observational and incidental learning by children with autism during small group instruction. AB - This study evaluated the acquisition of incidental and observational information presented to 6 children with autism in a small group instructional arrangement using a constant time delay (CTD) procedure. A multiple probe design across behaviors, replicated across 6 participants, was used to evaluate the effectiveness of the CTD procedure and to assess each student's ability to read another student's words and identify related pictures. Generalization was assessed in natural conditions using a pre- and post-test paradigm. Results indicate that, despite their documented deficits in social awareness and imitation, students learned observational and incidental information during small group instruction. Educational implications with regard to small group instruction are discussed. PMID- 17347880 TI - Impact of SMART Board technology: an investigation of sight word reading and observational learning. AB - The effects of SMART Board technology, an interactive electronic whiteboard, and a 3s constant time delay (CTD) procedure was evaluated for teaching sight word reading to students with moderate intellectual disabilties within a small group arrangment. A multiple probe design across three word sets and replicated with three students was used to evaluate the effectiveness of SMART Board technology on: (a) reading target grocery words; (b) matching grocery item photos to target grocery words; (c) reading other students' target grocery words through observational learning; and (d) matching grocery item photos to observational grocery words. Results support use of this tool to teach multiple students at one time and its effects on observational learning of non-target information. PMID- 17347881 TI - Brief report: plasma leptin levels are elevated in autism: association with early onset phenotype? AB - There is evidence of both immune dysregulation and autoimmune phenomena in children with autism spectrum disorders (ASD). We examined the hormone/cytokine leptin in 70 children diagnosed with autism (including 37 with regression) compared with 99 age-matched controls including 50 typically developing (TD) controls, 26 siblings without autism, and 23 children with developmental disabilities (DD). Children with autism had significantly higher plasma leptin levels compared with TD controls (p<.006). When further sub-classified into regression or early onset autism, children with early onset autism had significantly higher plasma leptin levels compared with children with regressive autism (p<.042), TD controls (p<.0015), and DD controls (p<.004). We demonstrated an increase in leptin levels in autism, a finding driven by the early onset group. PMID- 17347882 TI - Offering to share: how to put heads together in autism neuroimaging. AB - Data sharing in autism neuroimaging presents scientific, technical, and social obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with other measures of phenotype and with genetics, defines requirements for comparability of derived data and recommendations for raw data, outlines a core protocol including multispectral structural and diffusion-tensor imaging and optional extensions, provides for the collection of prospective, confound-free normative data, and extends sharing and collaborative development not only to data but to the analytical tools and methods applied to these data. A theme in these requirements is the need to preserve creative approaches and risk-taking within individual laboratories at the same time as common standards are provided for these laboratories to build on. PMID- 17347884 TI - Perceived availability, risks, and benefits of gambling among college students. AB - The current study was an exploration of gambling-related perceptions and their relation to gambling behavior among young adult college students. Three hundred and two ethnically diverse undergraduates at a large urban public university completed a survey to assess their perceptions of the availability, risks, and benefits of gambling, and the South Oaks Gambling Screen (SOGS) to assess gambling behavior and problems. Participants generally rated gambling as more available than alcohol or marijuana, and less risky than alcohol or cigarettes. The most common perceived benefits of gambling were social enhancement, financial gain, and positive changes in affect. Perceived benefits were a significant predictor of gambling problems. Perceived availability, perceived risk, and perceived benefits were found to be significant predictors of regular gambling. These results provide valuable information about the ways that college students perceive gambling and demonstrate that perceptions can be important predictors of gambling behavior. PMID- 17347885 TI - Vulnerability and comorbidity factors of female problem gambling. AB - This study helps to address a deficiency of gender-specific research into problem gambling. It focuses on the gambling behaviors, family and personal histories and comorbid psychological disorders of 365 female gamblers from across Ontario, Canada, who responded to a mail-in survey. Specifically, this study looks at rates of depression and anxiety, concurrent struggles with other behaviors (such as alcohol and drug use, disordered eating, overspending and criminal activity) and abuse history reported by female gamblers. The reported rates are considerably higher than for the general female population. The findings of this study agree with previous research. They suggest that prevention strategies and treatment practices for female problem gamblers should take into account women's mental health, addiction and trauma history as contributing factors in the development of problematic gambling. PMID- 17347886 TI - Ectopic hepatocellular carcinoma of the diaphragm. AB - Ectopic hepatocellular carcinoma (HCC) is very rarely reported. It may occur at various sites. To the best of our knowledge, only one case of ectopic HCC of the diaphragm has been reported. We present another such case with invasion to the lung. Subtotal resection of the left hemidiaphragm, wedge resection of the lung (left lower lobe), and splenectomy were undertaken. Postoperative course was unremarkable; the patient received two courses of adjuvant chemotherapy with cisplatin, VP-16, and bleomycin 1 month later. Follow-up computed tomography and ultrasound were performed 8 months later; there was no local recurrence or distal metastasis. PMID- 17347887 TI - Acute liver failure occurring immediately following anti-D immune globulin infusion in a patient with chronic hepatitis B infection. PMID- 17347888 TI - Group feeding behavior of brown trout is a correlated response to selection for growth shaped by the environment. AB - Group feeding pattern is a response correlated to selection for growth in brown trout. Previous results suggest that the feeding pattern of two lines (NL and SY), selected with the same process at two different fish farms, differ. This study addresses the following questions: (i) are the patterns differentially fixed by the selection process and if yes (ii) is this explained by the different genetic background of the lines? In a first experiment, we tested if the group feeding behavior can be inherited. We produced and reared under the same experimental conditions selected hybrids (NLS x SYS) and pure SY selected line (SYS). We compared their behavior on self-feeders when reared single or mixed (groups of 500 fish; mean initial BW = 6 g, 90-day period). Growth rates were comparable among the groups. In the lines reared single, NLS x SYS exhibited greater morning feeding activity than SYS. Feeding activity of SYS was higher later in the day. The inter-day variation of the morning peak was less variable for the hybrid than for the SYS line. In the mixed group, the pattern was intermediate between that of the hybrid and the pure line. In a second experiment we compared the feeding pattern of control hybrids (NLC x SYC) to pure control lines (SYC and NLC) reared single or mixed (groups of 500 fish; mean initial BW = 12 g, 92-day period). Feeding activity patterns were similar among the control groups. These results show that group feeding pattern is a heritable trait that can be indirectly selected with growth, which shape is less influenced by the growth performance and the genetic background than by the environmental conditions applied during the selection process. PMID- 17347889 TI - Impact of life events and difficulties on the mental health of Chinese immigrant women. AB - This study examined the life events and difficulties inherent to the immigration process and the sources of social support that influenced mental health. A six month longitudinal study, utilizing a detailed semi-structured interview protocol and standardized questionnaires, was conducted with a group of Chinese women who had migrated to Canada with their spouses in the last decade. All of the women and all of their spouses experienced major downward mobility. Correspondingly, the most frequent negative life event was employment-related and the most frequent difficulty was the financial strain of living below the poverty line, factors which significantly predicted the women's mental health. Social support had neither a main effect on mental health nor a buffer effect on the relationship between life events and difficulties and mental health. Implications for immigration and settlement policy are discussed. PMID- 17347890 TI - English- and Spanish-speaking Latina mothers' beliefs about food, health, and mothering. AB - Parent beliefs regarding food, health, and child feeding behaviors among Latinos have not been well-documented. A series of eight focus groups were conducted with English-speaking and Spanish-speaking low-income Latina mothers of preschoolers to investigate their beliefs regarding how food and food preparation are related to their children's health and to their own roles as mothers. Systematic content analysis using NUDIST 6 revealed seven themes discussed by the focus groups. Integration of these themes revealed three major areas of consideration: (1) a lack of connection between the domains of eating, overweight, and health outcomes; (2) the role of parent modeling of eating behaviors; and (3) the use of feeding strategies that may not be conducive to the development of healthy eating behaviors. Furthermore, the data suggest that there are important distinctions among Latinos based on language preference, and that a "one-size-fits-all" approach to modeling Latino mothers' feeding beliefs may not be appropriate. PMID- 17347891 TI - Fungal diversity, dominance, and community structure in the rhizosphere of clonal Picea mariana plants throughout nursery production chronosequences. AB - Fungal diversity in the rhizosphere of healthy and diseased clonal black spruce (Picea mariana) plants was analyzed with regard to nursery production chronosequences. The four key production stages were sampled: mother plants (MP), 8-week-old cuttings (B + 0), second-year cuttings (B + 1), and third-year cuttings (B + 2). A total of 45 fungal taxa were isolated and identified based on cultural, phenotypic, and molecular characters. Members of phylum Ascomycota dominated, followed by Basidiomycota and Zygomycota. Diagnosis characters and distance analysis of the internal transcribed spacer rDNA sequences allowed the identification of 39 ascomycetous taxa. Many belong to the order Hypocreales, families Hypocreaceae and Nectriaceae, which contain many clusters of potentially pathogenic taxa (Cylindrocladium, Fusarium, and Neonectria) and are also ecologically associated with antagonistic taxa (Chaetomium, Hypocrea, Microsphaeropsis, Penicillium, Paecilomyces, Verticillium, Trichoderma, and Sporothrix). This is also the first report of a Cylindrocladium canadense association with disease symptoms and relation with Pestalotiopsis, Fusarium, Exserochilum, Rhizoctonia, and Xenochalara fungal consortia. Both production chronosequence and plant health considerably influenced fungal taxa assemblages. Unweighted pair-group arithmetic average clustering showed that isolates from MP, B + 0, and B + 1 plant rhizospheres clustered together within healthy or diseased health classes, whereas isolates from healthy and diseased B + 2 plants clustered together. Canonical correspondence analysis revealed substantial alteration in community assemblages with regard to plant health and yielded a principal axis direction that regrouped taxa associated with diseased plant rhizosphere soil, whereas the opposite axis direction was associated with healthy plants. Two diversity indices were defined and applied to assess the fungal taxa contribution (Tc) and persistence (Pi) throughout the production. PMID- 17347892 TI - Monitoring diel variations of physiological status and bacterial diversity in an estuarine microbial mat: an integrated biomarker analysis. AB - Microbial mats are highly productive microbial systems and a source of not-yet characterized microorganisms and metabolic strategies. In this article, we introduced a lipid biomarker/microbial isolation approach to detect short-term variations of microbial diversity, physiological and redox status, and also characterize lipid biomarkers from specific microbial groups that can be further monitored. Phospholipid fractions (PLFA) were examined for plasmalogens, indicative of certain anaerobes. The glycolipid fraction was processed for polyhydroxyalkanoates (PHA) and the neutral lipid fraction was used to evaluate respiratory quinone content. Data demonstrate an increase in the metabolic stress, unbalanced growth, proportion of anaerobic bacteria and respiratory rate after the maximal photosynthetic activity. Higher accumulation of polyhydroxyalkanoates at the same sampling point also suggested a situation of carbon storage by heterotrophs closely related to photosynthetic microorganisms. Besides, the characterization of lipid biomarkers (plasmalogens, sphingolipids) from specific microbial groups provided clues about the dynamics and diversity of less-characterized mat members. In this case, lipid analyses were complemented by the isolation and characterization of anaerobic spore formers and sulfate reducers to obtain insight into their affiliation and lipid composition. The results revealed that temporal shifts in lipid biomarkers are indicative of an intense change in the physiology, redox condition, and community composition along the diel cycle, and support the hypothesis that interactions between heterotrophs and primary producers play an important role in the carbon flow in microbial mats. PMID- 17347893 TI - Identification of bovine QTL for growth and carcass traits in Japanese Black cattle by replication and identical-by-descent mapping. AB - To map quantitative trait loci (QTL) for growth and carcass traits in a purebred Japanese Black cattle population, we conducted multiple QTL analyses using 15 paternal half-sib families comprising 7860 offspring. We identified 40 QTL with significant linkages at false discovery rates of less than 0.1, which included 12 for intramuscular fat deposition called marbling and 12 for cold carcass weight or body weight. The QTL each explained 2%-13% of the phenotypic variance. These QTL included many replications and shared hypothetical identical-by-descent (IBD) alleles. The QTL for CW on BTA14 was replicated in five families with significant linkages and in two families with a 1% chromosome-wise significance level. The seven sires shared a 1.1-Mb superior Q haplotype as a hypothetical IBD allele that corresponds to the critical region previously refined by linkage disequilibrium mapping. The QTL for marbling on BTA4 was replicated in two families with significant linkages. The QTL for marbling on BTA6, 7, 9, 10, 20, and 21 and the QTL for body weight on BTA6 were replicated with 1% and/or 5% chromosome-wise significance levels. There were shared IBD Q or q haplotypes in the marbling QTL on BTA4, 6, and 10. The allele substitution effect of these haplotypes ranged from 0.7 to 1.2, and an additive effect between the marbling QTL on BTA6 and 10 was observed in the family examined. The abundant and replicated QTL information will enhance the opportunities for positional cloning of causative genes for the quantitative traits and efficient breeding using marker-assisted selection. PMID- 17347894 TI - R/qtlDesign: inbred line cross experimental design. AB - An investigator planning a QTL (quantitative trait locus) experiment has to choose which strains to cross, the type of cross, genotyping strategies, and the number of progeny to raise and phenotype. To help make such choices, we have developed an interactive program for power and sample size calculations for QTL experiments, R/qtlDesign. Our software includes support for selective genotyping strategies, variable marker spacing, and tools to optimize information content subject to cost constraints for backcross, intercross, and recombinant inbred lines from two parental strains. We review the impact of experimental design choices on the variance attributable to a segregating locus, the residual error variance, and the effective sample size. We give examples of software usage in real-life settings. The software is available at http://www.biostat.ucsf.edu/sen/software.html . PMID- 17347895 TI - Estimating the number of coding mutations in genotypic and phenotypic driven N ethyl-N-nitrosourea (ENU) screens: revisited. AB - We recently described methods for estimating the number of N-ethyl-N-nitrosourea (ENU)-induced coding mutations in phenotypic and genotypic screens. In this article we revisit these methods, clarifying their application. In particular, we focus on the difference between unconditional and conditional probabilities. We also introduce a website to assist investigators in the application of these equations ( http://www.well.ox.ac.uk/enuMutRat ). PMID- 17347896 TI - Central lymph node dissection in differentiated thyroid cancer. AB - BACKGROUND: There has been renewed interest in extensive lymph node dissection for papillary thyroid cancer (PTC), and a number of reports have been published concerning compartment-oriented dissection of regional lymph nodes in PTC. A comprehensive review of this body of literature using evidence-based methodology is pending. METHODS: Systematic review of the literature using evidence-based criteria. RESULTS: Issue 1: Systematic compartment-oriented central lymph node dissection (CLND) may decrease recurrence of PTC (Levels IV and V data, no recommendation) and likely improves disease-specific survival (grade C recommendation). Limited level III data suggest survival benefit with the addition of prophylactic dissection to thyroidectomy (grade C recommendation). The addition of CLND to total thyroidectomy can significantly reduce levels of serum thyroglobulin and increase rates of athyroglobulinemia (level IV data, no recommendation). Issue 2: There may be a higher rate of permanent hypoparathyroidism and unintentional permanent nerve injury when CLND is performed with total thyroidectomy than for total thyroidectomy alone (grade C recommendation). Issue 3: Reoperation in the central neck compartment for recurrent PTC may increase the risk of hypoparathyroidism and unintentional nerve injury when compared with total thyroidectomy with or without CLND (grade C recommendation), supporting a more aggressive initial operation. CONCLUSION: Evidence-based recommendations support CLND for PTC in patients under the care of experienced endocrine surgeons. PMID- 17347897 TI - Commercial mesh versus nylon mosquito net for hernia repair. A randomized double blind study in Burkina Faso. PMID- 17347898 TI - Vaccines for cholesterol management. AB - Over the last 50 years, several attempts have been made to harness the power and economy of vaccines in the fight against cardiovascular disease. Vaccines directed to lipoproteins, cholesterol itself, and molecules involved in cholesterol metabolism have all demonstrated success in modifying progression of disease in animal models of atherosclerosis. One vaccine that elicits antibodies to cholesteryl ester transfer protein has also progressed into the realm of human clinical testing. This review summarizes the published scientific work describing the various approaches that have been tried, their strengths and weaknesses, and where this field may go in the future. PMID- 17347899 TI - Islet vasculature as a regulator of endocrine pancreas function. AB - The islets of Langerhans consist of endocrine cells embedded in a network of specialized capillaries that regulate islet blood flow. Despite evidence for a critical role of islet perfusion in endocrine pancreas function, there is information to support no fewer than three models of endocrine cell perfusion, emphasizing the lack of a universally accepted physiological theory. Islet blood flow is regulated by signals, such as hormones and nutrients that reach the islet vasculature from distant tissues via the bloodstream. In addition, islet perfusion determines communication between endocrine and exocrine cells and between different types of endocrine cells within islets. Interest in islet microcirculation has increased after improvements in islet transplantation, a therapy for diabetes mellitus that requires revascularization of grafted islets in a new host organ. Abnormal revascularization is thought to be partly responsible for differences in graft and native islet function. Similarly, angiogenesis has been shown to be a critical step in the transformation of islet hyperplasia to neoplasia. PMID- 17347900 TI - Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping. AB - BACKGROUND: In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. METHODS: We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. RESULTS: Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. CONCLUSION: Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors. PMID- 17347901 TI - Lower prevalence of diverticulosis in patients with ulcerative colitis. AB - PURPOSE: Colonic diverticulosis is characterized by abnormal thickening of the bowel wall, associated with luminal overpressure and increase of sigmoid contractility. However, patients with ulcerative colitis show chronic inflammatory alterations determining a reduction of both bowel wall muscle tone and contractility. Thus, we could presume ulcerative colitis and colonic diverticulosis as two pathophysiologically and mutually excluding diseases. This study was designed to evaluate the prevalence of colonic diverticulosis in patients with ulcerative colitis compared with a control endoscopic population. METHODS: We prospectively analyzed the prevalence of colonic diverticulosis in 85 patients, older than aged 45 years, with known ulcerative colitis compared with that in 85 age/gender-matched patients without colitis. All patients underwent pancolonoscopy with ulcerative colitis and colonic diverticulosis diagnosis made by endoscopy and histopathology. The patients with ulcerative colitis also were divided in three subgroups according to the age at diagnosis (<30 years, 30-45 years, >45 years) and extension of disease (sigmoiditis, left colitis, extensive colitis). RESULTS: Colonic diverticulosis was present in 7 of 85 patients with and in 24 patients without ulcerative colitis (8.2 vs. 28.2 percent; P < 0.001; relative risk, 3.4; 95 percent confidence interval, 1.56-7.52). All seven patients with both diseases were diagnosed with ulcerative colitis when older than age 45 years. No differences were found between the two groups in terms of extension of diverticula. CONCLUSIONS: Patients with ulcerative colitis show a significantly lower prevalence of colonic diverticulosis, with this finding probably reflecting the motor alterations caused by chronic bowel wall inflammation. In the patients affected by ulcerative colitis with late onset of the disease, the reduced prevalence of colonic diverticulosis is not evident. PMID- 17347902 TI - Endobronchial metastases from colon cancer without liver metastases: report of eight cases. AB - PURPOSE: The liver is the most common site of hematogenous spread from colon tumors. Pulmonary metastases from colon cancer result, in most of the cases, from hepatic metastases. METHODS: We describe eight cases of colorectal cancers in which endobronchial metastases have been developed without any evidence of liver involvement. RESULTS: Median age was 62 years old. In most of the patients, the primary cancer developed in the left side. The median time from colorectal presentation to pulmonary onset was four years. Dyspnea was the major symptom in all cases. Pulmonary involvement included endobronchial metastasis in all cases. CT scan of the chest showed bilateral, diffuse, large, nodular infiltrates without lymph nodes enlargement and without pleural effusion. Endobronchial therapy brought symptomatic relief in all cases; however, two-year follow-up showed only 50 percent survival rate. CONCLUSIONS: Endobronchial metastasis should be suspected in patients with colon cancer with respiratory symptoms, even without known liver metastasis. To the best of our knowledge, such a case series has not been published yet. PMID- 17347903 TI - Adjuvant immunochemotherapy with protein-bound polysaccharide K for colon cancer in relation to oncogenic beta-catenin activation. AB - PURPOSE: Protein-bound polysaccharide K is an immunotherapeutic agent that promotes apoptosis by inhibiting nuclear factor-kappaB activation in cancer cells. We previously showed that oncogenic beta-catenin activates nuclear factor kappaB and inhibits apoptosis by up-regulating beta-transducin repeat-containing protein. We investigated whether the activation state of beta-catenin in the primary tumor is associated with differences in survival rates of patients with colon cancer undergoing immunochemotherapy with 5-fluorouracil plus polysaccharide K vs. chemotherapy with 5-fluorouracil alone. METHODS: We assessed the activation states of beta-catenin and nuclear factor-kappaB in the primary tumors of 202 colon cancer patients, and analyzed the data in terms of the clinicopathologic characteristics and survival of patients undergoing the two forms of adjuvant therapy. RESULTS: We found two distinct patterns of nuclear accumulation of activated beta-catenin in the tumor cells: diffuse nuclear accumulation in 89 cases (44 percent) and selective nuclear accumulation at the tumor invasion front in 18 cases (9 percent). Nuclear factor-kappaB activation was found in 64 cases (32 percent). In patients with diffuse nuclear accumulation type beta-catenin activation, immunochemotherapy significantly improved recurrence-free survival, cancer death survival, and overall survival rates compared with patients receiving chemotherapy alone. No survival benefit was found in cases with nuclear accumulation at the tumor invasion front-type beta catenin activation or no activation. Similarly, immunochemotherapy favored the survival of patients with nuclear factor-kappaB activation. Multivariate analysis established the TNM stage and administration of polysaccharide K as independent prognostic factors in the patients with diffuse nuclear accumulation-type beta catenin activation. CONCLUSIONS: The presence of diffuse nuclear accumulation type beta-catenin activation identifies patients with colon cancer who respond better to immunotherapy with polysaccharide K. PMID- 17347905 TI - Chewing and food consistency: effects on bolus transport and swallow initiation. AB - Preswallow bolus formation usually occurs in the mouth for liquids and in the oropharynx for solid foods. We examined the effect of chewing on the relationship between bolus transport and swallow initiation. Fifteen healthy subjects were imaged with lateral projection videofluorography while eating liquids, solid foods, and a mixture of liquid and solid foods in upright and facedown postures. Videotapes were reviewed to measure the location of the leading edge of the barium at swallow initiation. Chewing and initial consistency each altered the relationship between food transport and swallow initiation. In particular, when chewing liquid (or consuming foods with both liquid and solid phases), a portion of the food commonly reached the hypopharynx well before swallow onset. This transport to the hypopharynx was highly dependent on gravity, but transport to the valleculae for chewed solid food was active, depending primarily on tongue palate contact. Chewing appeared to reduce the effectiveness of the posterior tongue-palate seal, allowing oral contents to spill into the pharynx. Consuming two-phase foods with both solid and liquid phases may increase the risk of aspiration in dysphagic individuals with impaired airway protective reflexes. PMID- 17347906 TI - Management of acid- and alkali-induced esophageal strictures in 79 adults by endoscopic dilation: 8-years' experience in New Delhi. AB - Experience with endoscopic dilation of acid- and alkali-induced strictures of the esophagus using Savary-Gilliard (SG) and balloon dilators is limited, especially in adults. The aim of this study was to determine the safety and efficacy of endoscopic dilation in the management of corrosive esophageal strictures and to compare results with regard to acid- vs. alkali-induced strictures. The records of 230 patients who were treated by endoscopic dilation between 1997 and 2005 at our center were reviewed. This study included all the patients who had corrosive induced esophageal strictures. SG dilators were used in most of our patients [67/79 (85%)], while only a few patients [12/79 (15%)] were treated with balloon dilators. Dilation was found to be successful after an initial course of dilation (not requiring further dilations) in 28/37 (75.67%) cases in the SG dilator group and in 9/12 (75%) in the balloon group. Strictures caused by acids required a greater mean number of dilations for initial relief of dysphagia compared with that for alkalis. Some of these patients responded to a second course of dilation, leading to final combined SG dilator and balloon dilator success rates of 24/28 (86%) in the acid group and 17/21 (81%) in the alkali group. A total of 359 sessions of dilations were performed with a complication rate of 2/359 (0.56%). Endoscopic dilation using Savary-Gilliard and balloon dilators is safe and effective in managing corrosive esophageal strictures, but it is operator dependent and the final outcome depends largely on the technical expertise and appropriate selection of patients. PMID- 17347907 TI - Multiple sources of carbonic anhydrase activity in pea thylakoids: soluble and membrane-bound forms. AB - Carbonic anhydrase (CA) activity of pea thylakoids, thylakoid membranes enriched with photosystem I (PSI-membranes), or photosystem II (PSII-membranes) as well as both supernatant and pellet after precipitation of thylakoids treated with detergent Triton X-100 were studied. CA activity of thylakoids in the presence of varying concentrations of Triton X-100 had two maxima, at Triton/chlorophyll (triton/Chl) ratios of 0.3 and 1.0. CA activities of PSI-membranes and PSII membranes had only one maximum each, at Triton/Chl ratio 0.3 or 1.0, respectively. Two CAs with characteristics of the membrane-bound proteins and one CA with characteristics of the soluble proteins were found in the medium after thylakoids were incubated with Triton. One of the first two CAs had mobility in PAAG after native electrophoresis the same as that of CA residing in PSI membranes, and the other CA had mobility the same as the mobility of CA residing in PSII-membranes, but the latter was different from CA situated in PSII core complex (Ignatova et al. 2006 Biochemistry (Moscow) 71:525-532). The properties of the "soluble" CA removed from thylakoids were different from the properties of the known soluble CAs of plant cell: apparent molecular mass was about 262 kD and it was three orders more sensitive to the specific CA inhibitor, ethoxyzolamide, than soluble stromal CA. The data are discussed as indicating the presence of, at least, four CAs in pea thylakoids. PMID- 17347908 TI - Growth in children with chronic renal failure and after renal transplantation. AB - Growth retardation is a major problem for many children with chronic renal failure (CRF) and transplantation. The aim of this study is to assess the relation between height, glomerular filtration rate (GFR), hormonal alterations in children with CRF on regular haemodialysis (HD), and the impact of functioning graft after kidney transplantation.Thirty-six hemodialysed children were included in the study beside 32 pediatric transplants. Mean duration on HD was 14.72 +/- 7.73 months for the CRF group, while the mean interval after transplantation was 1.97 +/- 0.9 years for the second group. Moreover, twenty healthy children of matched age and sex served as controls. Assessment of growth parameters included height, expressed as standard deviation scores (Ht SDS) for chronological age, serum levels of growth hormone (hGH), and parathormone (PTH). Growth performance was evaluated twice: at the start of the study and one year later. Children with CRF and transplantation had significantly higher levels of both serum hGH and PTH compared to their controls, while CRF children experienced significantly higher serum levels of both hGH and PTH compared to those with functioning graft. Furthermore, analysis of our results by non-parametric Kendall's correlation at the start and one year later revealed negative correlation concerning dialysis duration, serum creatinine, and PTH. On the other hand, positive correlation was achieved for serum calcium and GFR. PMID- 17347909 TI - Sacral dimple as a skin manifestation of the Smith-Lemli-Opitz syndrome. PMID- 17347910 TI - Diagnosis of families with familial hypercholesterolaemia and/or Apo B-100 defect by means of DNA analysis of LDL-receptor gene mutations. AB - BACKGROUND: One major problem of using hypercholesterolaemia alone as a primary criterion for diagnosing familial hypercholesterolaemia (FH) is that 15-40% of relatives may be misdiagnosed because plasma lipid levels in FH heterozygotes overlap with those in the general population. SETTING: General Hospital/University of Vienna, Department of Pediatrics, Outpatient lipid clinic. METHODS: As a part of the MED-PED (make early diagnosis-prevent early death) project we are currently investigating children, adolescents and their relatives who are suspected to be affected with FH in our out-patient clinic for metabolic diseases using MED-PED inclusion criteria and confirming the diagnosis by means of DNA analysis. PATIENTS: 263 patients with premature atherosclerosis and/or hypercholesterolaemia: 116 children (mean age 11.6 +/- 4.1 years; 57 girls and 59 boys) and 147 adults (64 women, mean age 41.5 +/- 13.7 years; 83 men, mean age 42.8 +/- 10.8 years). RESULTS: 119 patients with mutations have been detected; 56 children with either low density lipoprotein receptor (LDLR) and/or ApoB mutations (27 girls and 29 boys; mean total cholesterol (TC) 275 +/- 71 mg/dl, triglycerides (TG) 101 +/- 57 mg/dl, high-density lipoprotein cholesterol (HDL-C) 49 +/- 12 mg/dl, low-density lipoprotein cholesterol (LDL-C) 198 +/- 67 mg/dl) and one boy with a homozygous. LDLR mutation. A further 62 adults with LDLR and/or ApoB mutations were documented; 33 women (mean age 36.9 +/- 11.1 years; mean TC 283 +/- 76 mg/dl, TG 137 +/- 78 mg/dl, HDL-C 55 +/- 17 mg/dl, LDL-C 210 +/- 67 mg/dl) and 29 men (mean age 45.0 +/- 10.6 years; mean TC 301 +/- 87 mg/dl, TG 163 +/- 112 mg/dl, HDL-C 42 +/- 12 mg/dl, LDL-C 233 +/- 83 mg/dl). In 32 of these subjects (11 children (21%), 21 adults (42%)), serum lipid levels were lower than the diagnostic MED-PED limits adopted, so that they might have been misclassified without an additional DNA analysis. CONCLUSION: In our study, diagnosis of FH and related disorders (ApoB-100 defect) by means of conventional laboratory methods missed at least 21% in children and 42% in adults affected with LDLR and/or ApoB gene mutations. Genetic FH diagnosis provides a tool for specific diagnosis of mutation carrier status. PMID- 17347911 TI - Phenylketonuria: dietary and therapeutic challenges. AB - PKU subjects need special attention in the definition of optimal supplementation of nutrients, which may be insufficient in relation to the type of diet and may otherwise manifest symptoms of deficit. In particular, it is necessary to pay great attention to the long-chain polyunsaturated fatty acid (LC-PUFA) levels in relation to correct development of the central nervous system. On the basis of numerous beneficial effects currently known, a permanent supplementation with LC PUFAs, in particular with docosahexaenoic acid, should be considered. Moreover, new formulas, Phe-free peptides, and 'modulated' amino acid preparations might help in preventing nutritional deficiencies and imbalances, with the ultimate aim of improving growth. New strategies--such as supply of tetrahydrobiopterin--need to be optimized in terms of targets, patients and expected outcomes. PMID- 17347912 TI - Selective screening for inborn errors of metabolism on clinical patients using tandem mass spectrometry in China: a four-year report. AB - We have initiated clinical selective screening for inborn errors of metabolism in China by analysing amino acids and acylcarnitines in a dried blood filter-paper samples using tandem mass spectrometry. Samples from a total of 3070 children suspected of inborn errors of metabolism were collected through a study network which covered most provinces of China. The diagnoses were further confirmed through clinical symptoms, by gas chromatography-mass spectrometry and other biochemistry studies, and in a few cases by DNA analysis. In all, 212 cases were diagnosed (6.6%) including 92 (43.4%) with amino acids disorders (48 with phenylketonuria, 12 with ornithine carbamoyltransferase deficiency, 7 with tyrosinaemia type I, 9 with maple syrup urine disease, 5 with citrullinaemia type I, 8 with citrullinaemia type II, 2 with homocystinuria, and 1 with argininaemia); 107 (50.5%) with organic acid disorders (including 58 with methylmalonic acidaemia, 13 with propionic acidaemia, 6 with isovaleric acidaemia, 7 with glutaric acidaemia type I, 6 with 3-methylcrotonyl-CoA carboxylase deficiency, 2 with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, 10 with multiple carboxylase deficiency, and 5 with beta-ketothiolase deficiency); and 13 (6.1%) with fatty acid oxidation disorders (including 1 with carnitine palmitoyltransferase deficiency type I, 1 with carnitine palmitoyltransferase deficiency type II, 1 with short-chain acyl-CoA dehydrogenase deficiency, 5 with medium-chain acyl-CoA dehydrogenase deficiency, 3 with very long-chain acyl-CoA dehydrogenase deficiency, and 2 with multiple acyl-CoA dehydrogenase deficiency). It is suggested that tandem mass spectrometry is useful for selective screening of clinically suspected patients. The majority of diseases (94%) in this study were amino acid disorders and organic acid disorders. Fatty acid oxidation disorders are relatively rare in the Chinese, but medium-chain acyl-CoA dehydrogenase deficiency should be further investigated. PMID- 17347913 TI - Enzyme, cell and gene-based therapies for metachromatic leukodystrophy. AB - Metachromatic leukodystrophy (MLD) is a demyelinating storage disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ARSA). Lack of ARSA activity leads to the accumulation of galactosylceramide-3-O-sulfate (sulfatide) in the central and peripheral nervous systems. Based on the age at onset, the disease is usually classified into three forms: the late-infantile form, which manifests in the second year of life; the juvenile variants (onset between 4 and 12 years), which are subdivided into early-juvenile (EJ, onset before 6 years) and late juvenile (LJ, onset after 6 years); and the adult form (onset after 12 years of age). Currently, there is no efficient therapy for the late-infantile form of MLD (50% of the patients), death occurring within a few years after onset of neurological symptoms. Allogeneic haematopoietic cell transplantation (HCT), when performed at a very early stage of the disease, may improve selected patients with juvenile or adult forms of MLD. As with other lysosomal storage diseases, the physiopathology of MLD is poorly understood. Demyelination is the main pathological finding, but substantial storage of sulfatides in neurons also occurs, and may contribute to the clinical phenotype. The physiopathological process leading to neuronal and glial cell degeneration and apoptosis involves accumulation of undegraded sulfatides but also secondary abnormalities (storage/mislocalization of unrelated lipids, inflammatory processes). This review summarizes the recent advances in the understanding of the physiopathology of MLD and the new therapeutic perspectives currently under preclinical investigation, including enzyme replacement therapy, gene therapy and cell therapy. PMID- 17347914 TI - International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. AB - Mucopolysaccharidosis IVA (MPS IVA; Morquio A disease) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase. The natural history of this disease is incompletely understood. To study which variables influence the clinical outcome, we conducted a study in which MPS IVA patients were asked to fill out a questionnaire with inquiries regarding family history, diagnosis, signs and symptoms, height, weight, surgical history, physical activity, and general complaints. A total of 326 patients (172 male, 154 female) from 42 countries enrolled in the Morquio A Registry programme. The mean age of patients enrolled was 14.9 years for males and 19.1 years for females, with a wide range of 1-73 years. Sixty-four per cent of the patients were under 18 years. Initial symptoms were recognized between 1 and 3 years of age (mean age 2.1 years) and mean age at diagnosis for the patients was 4.7 years. A progressive skeletal dysplasia was commonly observed among the MPS IVA patients. Fifty per cent of patients underwent surgical operations to improve their quality of life. The most frequent surgical sites include neck (51%), ear (33%), leg (26%) and hip (25%). The birth length for affected males and females was 52.2 +/- 4.7 cm and 52.2 +/- 4.5 cm, respectively. The final adult height for affected males and females was 122.5 +/- 22.5 cm and 116.5 +/- 20.5 cm, respectively. The results of this study provide a reference for assessment of efficacy for studies of novel therapies. PMID- 17347915 TI - Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. AB - The Fabry Registry is a global observational research platform established to define outcome data on the natural and treated course of this rare disorder. Participating physicians submit structured longitudinal data to a centralized, confidential database. This report describes the baseline demographic and clinical characteristics of the first 1765 patients (54% males (16% aged < 20 years) and 46% females (13% < 20 years)) enrolled in the Fabry Registry. The median ages at symptom onset and diagnosis were 9 and 23 years (males) and 13 and 32 years (females), respectively, indicating diagnostic delays in both sexes. Frequent presenting symptoms in males included neurological pain (62%), skin signs (31%), gastroenterological symptoms (19%), renal signs (unspecified) (17%), and ophthalmological signs (11%). First symptoms in females included neurological pain (41%), gastroenterological symptoms (13%), ophthalmological (12%), and skin signs (12%). For those patients reporting renal progression, the median age at occurrence was 38 years for both sexes, but onset of cerebrovascular and cardiovascular events was later in females (median 43 and 47 years, respectively) than in males (38 and 41 years, respectively). This paper demonstrates that in spite of the considerable burden of disease in both sexes that begins to manifest in childhood or adolescence, the recognition of the underlying diagnosis is delayed by 14 years in males and 19 years in females. The Fabry Registry provides data that can increase awareness of common symptoms in all age groups, as well as insight into treated and untreated disease course, leading to improved recognition and earlier treatment, and possibly to improved outcomes for affected individuals. PMID- 17347916 TI - Molecular and clinical aspects of peroxisomal diseases. AB - Peroxisomal diseases, an expanding group of inborn errors of metabolism, can be classified into three categories--peroxisome biogenesis disorders (PBDs), single peroxisomal enzyme deficiencies, and contiguous gene syndrome. PBDs comprise 13 complementation groups and their responsible genes have been identified, including our newly identified group with a PEX14 defect. We have established a diagnostic system of peroxisomal diseases in Japan, and have identified 40 Japanese with PBDs, 11 patients with beta-oxidation enzyme deficiencies and more than 100 patients with adrenoleukodystrophy. Further study of and enlightenment on peroxisomal diseases is necessary to overcome these disorders. PMID- 17347917 TI - Peak bone mass in patients with phenylketonuria. AB - OBJECTIVE: Several studies have suggested a compromised bone mass in phenylketonuria patients but most reported on heterogeneous or small patient groups. Our aim was to evaluate peak bone mass in adult PKU patients and to relate BMD to nutritional parameters. PATIENTS AND METHODS: BMD was measured by dual-energy x-ray absorptiometry in 31 adult PKU patients (18 female), mean age 25 +/- 5.3 years. Nutritional intake was calculated based on food diaries. Diet adherence was determined based on patients' report. RESULTS: Mean blood phenylalanine (Phe) concentration was 968 +/- 526 micromol/L (16 +/- 8.7 mg/dl). Eight patients (32.2%) met the recommended blood Phe concentration of <726 micromol/L (<12 mg/dl), and there was no significant difference in Phe concentrations between diet-adherent and non-adherent patients. Osteopenia was detected in 11 patients (38.7%), while osteoporosis was detected in 2 patients (6.5%). No correlation was found between BMD and age, blood minerals, Phe, vitamin D and alkaline phosphatase levels, calcium and protein intake, body mass index, and body fat percentage. CONCLUSIONS: Peak bone mass is decreased in PKU patients. Possible explanations include long-standing dietary deficiency in protein, calcium, vitamin D or trace elements, or a primary defect in bone turnover inherent to the disease itself. Our data do not favour any of these hypotheses. Further studies are needed to elucidate the cause of low bone density in PKU patients. PMID- 17347918 TI - Detection of familial combined hyperlipoproteinaemia patients in the Brisighella Heart Study historical cohort: an epidemiological approach. PMID- 17347919 TI - Intuition and the junctures of judgment in decision procedures for clinical ethics. AB - Moral decision procedures such as principlism or casuistry require intuition at certain junctures, as when a principle seems indeterminate, or principles conflict, or we wonder which paradigm case is most relevantly similar to the instant case. However, intuitions are widely thought to lack epistemic justification, and many ethicists urge that such decision procedures dispense with intuition in favor of forms of reasoning that provide discursive justification. I argue that discursive justification does not eliminate or minimize the need for intuition, or constrain our intuitions. However, this is not a problem, for intuitions can be justified in easy or obvious cases, and decision procedures should be understood as heuristic devices for reaching judgments about harder cases that approximate the justified intuitions we would have about cases under ideal conditions, where hard cases become easy. Similarly, the forms of reasoning which provide discursive justification help decision procedures perform this heuristic function not by avoiding intuition, but by making such heuristics more accurate. Nonetheless, it is possible to demand too much justification; many clinical ethicists lack the time and philosophical training to reach the more elaborate levels of discursive justification. We should keep moral decision procedures simple and user-friendly so that they will provide what justification can be achieved under clinical conditions, rather than trying to maximize our epistemic justification out of an overstated concern about intuition. PMID- 17347920 TI - ITS2 sequences as barcodes for identifying and analyzing spider mites (Acari: Tetranychidae). AB - The use of DNA barcodes, short DNA sequences from a standardized region of the genome, has recently been proposed as a tool to facilitate species identification and discovery. Here we show that second internal transcribed spacer of nuclear ribosomal DNA (rDNA-ITS2) barcodes effectively discriminate among 16 species of spider mites (Acari: Tetranychidae) from Israel. The barcode sequences of each species were unambiguously distinguishable from all other species and formed distinct, nonoverlapping monophyletic groups in the maximum-parsimony tree. Sequence divergences were generally much greater between species than within them. Using a 0.02 (2%) threshold for species diagnosis in our data set, 14 out of 16 species recognized by morphological criteria would be accurately identified. The only exceptions involved the low divergence, 0.011-0.015 (1.1 1.5%), between Tetranychus urticae and Tetranychus turkestani, where speciation may have occurred only recently. Still, these species had fixed alternative rDNA ITS2 variants, with five diagnostic nucleotide substitutions. As a result, we tentatively conclude that rDNA-ITS2 sequence barcodes may serve as an effective tool for the identification of spider mite species and can be applicable as a diagnostic tool for quarantine and other pest management activities and decision making. We predict that our work, together with similar efforts, will provide in the future the platform for a uniform, accurate, practical and easy-to-use method of spider mite species identification. PMID- 17347921 TI - Using invaded range data to model the climate suitability for Amblyomma variegatum (Acari: Ixodidae) in the New World. AB - Climate matching models are in increasing use to predict distributions of living organisms, using records of the known distribution of a species to map its expected range of habitat suitability. Here, we modelled the known distribution of the tick Amblyomma variegatum in Africa as a preliminary step to delineate the most probable range of climatically suitable habitat for the tick in the New World. We used two presence-only methods (one based in the Gower distance, the other based on the Maximum Entropy principle) to model the distribution range in Africa. The Maximum Entropy method is highly dependent of the realized niche of the tick, and has serious constraints in the case of lack of adequate description of the actual range of the tick. The Gower distance, however, can evaluate the fundamental niche of the tick and produced better results with the same set of distribution data. Several populations of A. variegatum were recognized in Africa on the basis of statistically different ecological attributes. The separate modelling of the climate envelope for these populations provided a better fit in the delineation of habitat suitability with both methods in Africa but produced high rates of false negatives when applied to the Caribbean. The best modelling strategy for the tick in the New World (according to the rate of false negatives) is the use of Gower distance together with the known distribution of the tick in the Caribbean. The potential spread area of the tick includes all the Caribbean, large areas of Colombia and Venezuela, parts of Brazil, most of the Mesoamerican corridor and Mexico as well as the Peninsula of Florida. We do not consider further if the invading strain either still retains the full ecological plasticity of the original populations in Africa, or has already adapted to the invaded area, resulting in a more restricted ability to expand. Both possibilities have deep impact in our analyses, as the tick could find a larger zone for spreading into the New World. PMID- 17347922 TI - A novel moderately halophilic bacterium for decolorizing azo dye under high salt condition. AB - Halomonas sp strain GTW was newly isolated from coastal sediments contaminated by chemical wastewater and was identified to be a member of the genus Halomonas by 16S rDNA sequence analysis and physical and biochemical tests. The optimal decolorization conditions were as follows: temperature 30 degrees C, pH 6.5.0 8.5, NaCl 10-20% (w/v) and the optimal carbon source was yeast exact. The results of experiments demonstrated that the bacteria could decolorize different azo dyes under high salt concentration conditions, and the decolorization rate of five tested azo dyes could be above 90% in 24 h. The exploitation of the salt-tolerant bacteria in the bio-treatment system would be a great improvement of conventional biological treatment systems and the bio-treatment concept. PMID- 17347924 TI - [The birth of the word 'psychosomatic' in medical literature by Johann Christian August Heinroth]. AB - Up to the present day the contributions Johann Christian August Heinroth (1773 1843) made to the development of psychosomatics have been little acknowledged. This paper points out that it was Heinroth who introduced the term 'psychosomatic' into medical literature and examines his concept for psychosomatic ideas. Quotations from his work, among them the passage in his famous 1818 Textbook of Disturbances of Mental Life, are presented and interpreted in their context. All this shows clearly that Heinroth's approach reveals distinct psychosomatic ideas, especially in his concept of body and soul, the etiology and pathogenesis of mental illnesses. For Heinroth soul has the primacy over the body and both interact in many ways. Consequently, mental and many somatic illnesses are caused by the soul, i. e. psychogenetically. Hence Heinroth is of major importance for the history of psychosomatic medicine, not only because he introduced the name, but also due to his holistic and anthropological approach. PMID- 17347923 TI - Expression of lipoprotein lipase associated with lung adenocarcinoma tissues. AB - Lipoprotein lipase (LPL) plays a key role in the lipid metabolism and transporting. It can catalyze the hydrolysis of chylomicron and very low-density lipoprotein triglyceride. Moreover, the abnormality of LPL associates with many pathophysiological conditions. Herein cDNA microarray and Northern blots analysis were used to study the expression of lipoprotein lipase in lung adenocarcinoma tissues. There were 113 genes of all tested blots in cDNA microarray expressed lowly. LPL gene is expressed lowly at the average ratio 0.26 (Cy5/Cy3) in lung adenocarcinoma tissues over controls. Northern blots confirmed those changes detected from the cDNA microarray and suggested that low expression of LPL may play an important role in the lung adenocarcinoma development. PMID- 17347925 TI - [On the reliability of severely brain damaged persons as witnesses of their own injury]. AB - We report a court verdict in the second retrial of a murder case that was based exclusively on the witness account of a severely brain damaged victim, and its reversal by the German Federal Court. The assessment of evidence had to weigh up the probability of the presence of real accounts of the crime versus the possibility of alternative explanations, i. e. trauma related confabulation. The defendant was acquitted. PMID- 17347927 TI - [Age-dependent prioritisation of health-care spending--perspectives for the German health-care system]. AB - Expenditure on health care has been rising for years. Also, the ageing population is a matter of fact. Generally, ageing goes along with higher expenditure for health care. Debates about the financial situation and solution for this situation are common. This article examines the impact of all aspects of ageism with regard to the expenditure in health care. Besides, for the practical effects of rationing, a multidimensional approach is illustrated. The article discusses the concept of age-dependent prioritisation of health-care spending. PMID- 17347926 TI - [Susceptibility to strategy of the drug component of the IPHCC+RxGroups classification system in a risk-adjusted morbidity compensation scheme--a conceptional and data-supported analysis]. AB - BACKGROUND: A report commissioned by the German Ministry of Health recommends to the existing scheme for calculating risk-adjusted transfers to sickness funds supplement with the IPHCC+RxGroups method. The method is based on inpatient diagnoses and prescribed drugs as health status measures deduced from prior use. OBJECTIVE: The present study investigates the sickness fund's expected net return from gaming based on the drug component of the risk adjuster. METHODS: The study explores three possible strategies using the RxGroups method. For the stimulations, insurees are assigned to additional indications or to higher valued RxGroups within the same indication. Then, costs and financial benefits attributable to the altered drug use are estimated and compared with the status quo. The study uses 2000 and 2001 sample data of more than 370,000 insurees of Germany's company-based sickness funds system (BKK). RESULTS: While upgrading increases overall costs, it can be beneficial for the individual sickness funds. Their net return crucially depends on the number of sickness funds gaming the system: the more participating in the game, the smaller is the average net return. Moreover, not participating often is even worse, which in turn points to a prisoner's dilemma. CONCLUSIONS: When extending the risk adjustment scheme in social health insurance, the German legislator should take into account the perverse incentives of risk adjusters such as the described prescription drug model. PMID- 17347928 TI - [Results of a survey of insurance customers participating in a DMP for diabetes mellitus type 2 of BARMER Health Insurance, Neubrandenburg]. AB - The healthcare system in Germany is characterised by fragmentation and a lack of communication between the various sectors of care. Since the late 1990s, intensive efforts have been made to enhance integration. Disease Management Programs (DMPs) represent an attempt to improve the care for the chronically ill which is known to be deficient, in particular for diabetics. As quality assurance studies do not yet provide a comprehensive picture and, in the absence of convincing evaluations, surveys of health insurance customers are particularly interesting and can provide information about preferences, motivation and evaluation of the participants in the DMPs. Thus, one year into a program started in July 2004, a representative survey was carried out of participants in the DMP for diabetics (customers of BARMER Health Insurance, Neubrandenburg). (Random sample net=124). The participants were generally age 61 years or older (77.4%), and two-thirds of them had suffered from diabetes or received treatment for more than 5 years. During the program, the proportion consulting a diabetes specialist had doubled to 31%. The assessment of the quality of care had improved markedly; 19% of the participants reported an improvement in their health status. The main reasons given for participating in the program were an anticipated improvement in the quality of care and an activation of the patient's role. Analyses indicate that those who reported the most benefit from the program are the core group of the elderly chronically ill. But as this group was particularly well informed about their own disease, attention should always be paid to the possibility of social selection processes in such health programs. In future, quality assurance studies should be carried out in order to validate surveys addressing participants in DMPs and, conversely, surveys of DMP participants should be conducted to validate quality assurance findings. PMID- 17347929 TI - [Health indicator-based cluster analysis of districts and urban districts in North Rhine-Westphalia]. AB - OBJECTIVE: North Rhine-Westphalia (NRW's) indicator set for health reporting activities comprises more than 70 regional health indicators, which means that these data are available for health reporting purposes for all 54 districts and urban districts. Morbidity and mortality indicators differ in part quite considerably and require further interpretation. With the help of selected indicators, the authors of the following article try to explain the relation between social status and health status. METHODOLOGY: Ten years ago, NRW, as part of its health reporting activities, started to carry out multivariate analyses to classify socio-demographically different types of regions, leading to the establishment of six types of regions which can be linked to health-related data. Social structure indicators are part of a first step submitted to a main component analysis and grouped together by a small number of features and/or factors which clearly reflect differences in living conditions. As a result, two factors were extracted: an economic prosperity factor which is mainly determined by the disposable income and a so-called A-factor which mainly describes the fact that poorer, elderly, unemployed and foreign population groups live concentrated in regions with a declining population but high population density. These factors are, in a second step, used for a cluster analysis aimed at classifying the 54 districts and urban districts and at establishing different types of regions. In a subsequent step, the cluster method is used to explain regional variations of selected health indicators. RESULTS: It is a proven fact that morbidity and mortality are influenced by social status. With the help of selected indicators, six clusters with a different socio-economic structure influencing the health status of the population can be established for NRW. Special attention should be paid to the cluster of the Ruhr area with its below-average social situation. With 90% NRW's population primarily living within the other 5 clusters which are differently structured but increasingly adjusting their living conditions to each other. The authors of this publication assign four health status indicators to predefined clusters and analyse the relation between the social and health status: female and male life expectancy, the proportion of underweight live births, infant mortality and avoidable deaths.In regions with high A-factor values (poverty pole), i. e., in several ways socially deprived regions, male and female average life expectancy is significantly lower than in regions with a clearly less pronounced accumulation of problems. Moreover, a significantly higher life expectancy for male live births can be observed in regions with a high disposable income. The model fails to establish a convincing correlation between social status and infant mortality and breast cancer. CONCLUSIONS: Knowledge about socio-demographic differences in the health status of the population is particularly important for prevention measures in order to be able to react appropriately to health risks in districts and urban districts. The analysis shows that an intense regional accumulation of problems will have a negative influence on health status, an influence which is more significant than the positive influence of prosperous regions on the health status. PMID- 17347930 TI - [Personal contextual factors (short version), part II]. AB - In this journal a group of medical experts recently compiled a proposal for a systemic classification of personal contextual factors into domains, categories and items with respect to the ethical guidelines of the ICF (part I). In a second step the main issues have been transferred into the preliminary draft for a short version which is presented in this paper to give support for practical daily use in health insurance matters (part II). PMID- 17347931 TI - ["Be smart--don't start". Results of a non-smoking competition in Germany 1997 2007]. AB - PURPOSE: The purpose of this article is to describe the diffusion and evaluation of the smoking prevention programme "Be Smart--Don't Start", the German "Smoke Free Class Competition". METHOD: The diffusion is described by means of numbers of participating classes and a representative population-based interview of 3,600 12-19-year-olds, which was conducted in 2005. Two controlled and two randomised controlled studies carried out in three countries (Germany, Finland and the Netherlands) with a total number of 12,812 adolescents (N of the intervention group: 8,086; N of the control group: 4,726) have been realised to evaluate the intervention. RESULTS: In 2005 20% of all 12-15 year-olds and 9% of all 16-19 year-olds living in Germany had participated in the programme. From baseline to follow-up test 12-24 months later smoking increased by 21.78 per cent points in the control group, compared to an increase of 16.02 per cent points in the intervention group. At follow-up 27.57% of the pupils from the intervention group, and 35.91% of the pupils from the control group are actual smokers (odds ratio=0.65, 95% confidence interval: 0.57-0.74). CONCLUSIONS: Participating rate in the competition is high. The results indicate that the competition might have a short-term effect and be able to delay the onset of smoking. PMID- 17347932 TI - [The use of assessment instruments in the rehabilitation of accident victims]. AB - Within the course of rehabilitation management the Verwaltungs Berufsgenossenschaft (VBG) has started to measure the outcomes to assure the quality of rehabilitation processes using assessment instruments. The measures included some aspects of activity and participation in accordance with the International Classification of Functioning, Disability and Health (ICF). The present paper describes the generic and condition-specific instruments used in the this study to assess the health-related quality-of-life, discusses their selection and illustrates their incorporation into management practice. The assessment process constitutes a consistent system to prove the effects of rehabilitation and their persistence. The first experience shows that the assessment-based quality management system can be recommended for permanent modelling of structures, processes and outcomes to improve the efficacy and cost effectiveness of rehabilitation. PMID- 17347933 TI - Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy. AB - INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist, YM218, was studied on proteinuria and focal glomerulosclerosis in early and late intervention after 5/6 nephrectomy in rats, and compared with an angiotensin converting enzyme inhibitor (ACE-I). MATERIALS AND METHODS: After 5/6 nephrectomy, early intervention was performed between week 2 and 10 thereafter with the V1a-receptor-selective antagonist (VRA, 10 mg/kg/day, n=10), enalapril (ACE-I, 10 mg/kg/day, n=9), or vehicle (n=8). Late intervention was performed in another group between week 6 and 12 with VRA (10 mg/kg/day, n=7), lisinopril (ACE I, 5 mg/kg/day, n=7), or vehicle (n=7). RESULTS: In early intervention, proteinuria and focal glomerulosclerosis were significantly decreased by VRA compared to vehicle (44+7% and 59+8% respectively). ACE-I significantly decreased proteinuria (67+7%) and a trend towards a decrease in focal glomerulosclerosis was observed (30+18%). In late intervention, VRA did not decrease proteinuria and focal glomerulosclerosis compared to vehicle (21+20% and 0%, respectively), ACE-I significantly lowered proteinuria (92+2%) and a focal glomerulosclerosis (69+1%) lowering trend was observed. CONCLUSION: These results indicate that VRA may protect against early progression of renal injury after 5/6 nephrectomy, whereas its effectiveness seems limited in established renal damage. PMID- 17347934 TI - The Renin Report. PMID- 17347936 TI - [Proceedings of the IXth International Course of Current Issues in Neuropediatrics and Infant Neuropsychology, Valencia, Spain]. PMID- 17347937 TI - [The specific role of the neuropaediatrician in visits for learning difficulties]. AB - INTRODUCTION: Coordinating professionals for the initial assessment and treatment of children with learning difficulties is a complicated task. DEVELOPMENT: Initial contact with the sources of information, the history and physical examination, a fast neuropsychological evaluation and requesting suitable tests allow the professional to reach an evaluation that will lead to a proposal for re education. Evaluating the results of the re-education, coordination among the re educators and the school, and explanations for the family are essential conditions for favourable progress to be made. CONCLUSIONS: In a visit for learning disorders, the role of the neuropaediatrician is crucial, especially to optimise the performance of the team as regards time and efficiency, and to improve the quality of the service offered to the child. PMID- 17347938 TI - [The predictive value of DSM-IV criteria in the diagnosis of attention deficit hyperactivity disorder and its cultural differences]. AB - INTRODUCTION: The most common method used to diagnose attention deficit/hyperactivity disorder (ADHD) is based on the Diagnostic and statistic manual of mental disorders, 4th edition (DSM-IV) criteria. Nevertheless, it is more likely that the categorical system postulated by DSM-IV is not the most appropriate method as it does not consider the possible differences between the diagnostic capacity of the 18 proposed criteria. AIM. To analyze the predictive power of each DSM-IV diagnostic symptoms/criteria for ADHD using DuPaul's ADHD Parent and Teacher Rating Scales. PATIENTS AND METHODS: In a prospective, poblational study to evaluate the prevalence of ADHD the positive predictive power of each item was analyzed for each subtype and informant. A kappa index was applied for positive predictive power to correct the number of accurate predictions based on chance factors, and a ranking of items was established to determinate which ones offered the highest predictive power, comparing parent and teacher ratings. RESULTS: The results suggest that not all DSM-IV criteria are equal with regard to their ability to predict ADHD. The predictive power varies as a function of the informant. Parent and teachers agreed more on hyperactivity and impulsivity items, and showed more significant differences with regard to the American sample. CONCLUSIONS: The approach that aggregates any combination of items will not be the more effective strategy for ruling in a diagnosis of ADHD. To improve the clinical value of these scales making item combinations is recommended, the ones that will have attached a higher clinical weight for ruling in a diagnosis of ADHD. PMID- 17347939 TI - [Discipline styles in families with children with attention deficit hyperactivity disorder: their influence on the course of the disorder]. AB - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is caused by hereditary factors but it can only really be understood using a model that takes into account the interaction between genes and the environment. Discipline styles stand out among the factors offered by the familial environment that can influence the course of ADHD. AIMS: To compare the discipline styles employed by mothers of children with and without ADHD and to analyse how the subtype of ADHD and the presence of oppositional defiant disorder influence the discipline styles utilised by mothers of children with ADHD. SUBJECTS AND METHODS: We divided 167 mothers into two groups, one consisting of those who had a child with ADHD (n = 114) and a control group (n = 53), and they were asked to answer a semi structured interview and a questionnaire about discipline styles. RESULTS: The statistical analyses showed that mothers of children with ADHD used more severe discipline strategies, especially if the ADHD was associated with oppositional defiant disorder. CONCLUSIONS: Interventions must include family guidance focused on the dimensions of self-control and affective expression. PMID- 17347940 TI - [Clinical variability and characteristics of attention deficit hyperactivity disorder in girls]. AB - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neurobiological condition essentially characterised by inattention, hyperactivity and impulsiveness, and has a prevalence of around 5%. Because it is a biological disorder, both boys and girls with ADHD display these same symptoms, but more boys are diagnosed with ADHD (in a ratio of 3 to 1). AIM: To examine the differences between the two sexes, their prevalence and possible female subtypes in ADHD. PATIENTS AND METHODS: We conducted a retrospective study of 172 patients of both sexes who were attended as hospital neuropaediatric outpatients in the year 2004 according to Diagnostic and statistical manual of mental disorders (DSM IV-TR) criteria. Their ages ranged between 4 and 14 years and they were divided into three groups: under 6, between 6 and 10, and from 11 to 14 years old. The girls were subdivided into four subtypes, in order of greater to lesser prevalence: shy, hypersociable, hyperactive and changeable. RESULTS: Both sexes showed the same response to methylphenidate. Only the group of boys presented other comorbidities such as negativism and conduct disorders; approximately 25% of them required treatment with atypical neuroleptic drugs. CONCLUSIONS: a) Girls have certain specific clinical manifestations within the three common symptoms; b) methylphenidate is equally effective in both sexes; c) only boys display other disorders such as negativism and conduct disorders; and d) the brains of males and females are quite similar, but symptoms are expressed differently depending on environments and levels. PMID- 17347941 TI - [The neurobiology of learning difficulties: neurofibromatosis type 1 as a model for researching and treating learning disorders]. AB - INTRODUCTION: Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, with a prevalence of around 1:3500. The most important concern for patients and their families is the increased risk of developing benign and malignant tumours in the central and peripheral nervous systems. Up to 80% of patients, however, experience difficulties in learning processes. Symptoms compatible with attention deficit hyperactivity disorder are present in as many as 60% of patients. Learning difficulties are the chief cause of morbidity throughout their lives. DEVELOPMENT: Some recent studies have made it possible to offer a better description of the cognitive and developmental phenotype in patients with NF1. Similarly, advances in our understanding of the underlying molecular and cellular processes in cognitive impairment and access to sophisticated molecular genetics techniques have allowed a number of scientific disciplines to work together in the search for an understanding and potential solution to the cognitive disorders in this population. CONCLUSIONS: Preclinical studies show the enormous potential of certain pharmacological interventions. Transferring the results obtained in the treatment of learning difficulties in animal models of NF1 to the treatment of patients is a step that is currently under development. If it were effective, it would open the door to numerous areas of research that would rapidly increase our knowledge and the possibilities of intervention in this and many other learning disorders. PMID- 17347942 TI - [The psychopharmacology of the comorbid disorders associated with attention deficit hyperactivity disorder]. AB - INTRODUCTION: The pharmacological treatment most commonly used in attention deficit hyperactivity disorder (ADHD) has traditionally consisted in the administration of psychostimulants. The particular association with comorbid disorders makes it essential to utilise different therapeutic approaches and this accounts for the growing therapeutic arsenal currently available for use in this condition. DEVELOPMENT: It is important to be familiar with the different comorbidities because they are especially frequent and also because of their effect on the prognosis. Thus, it is necessary to reach a good diagnosis as early as possible in order to implement a therapy that allows the problem to be curbed. To do so, we need to know about the different pharmaceuticals that have to some extent or other proved to be effective. CONCLUSIONS: This paper aims to offer a global view of the problem by analysing the characteristics of the comorbid disorders associated with ADHD and the pharmacological tools that enable us to modify their deleterious effects. PMID- 17347943 TI - [Genetic and molecular aspects in attention deficit hyperactivity disorder: the search for the genes involved in clinical diagnosis]. AB - INTRODUCTION AND DEVELOPMENT: Attention deficit hyperactivity disorder (ADHD) is still today one of the most widely researched medical problems around the world. It is the most common neuropsychiatric diagnosis in school-age children. The fact that it will affect the patient throughout their whole life together with the social and economic impact it has on the individual and on society are clearly acknowledged and are a motive for concern. The clinician who is faced with treating these patients has no doubt that this entity presents in familial groups. This gives rise to obvious difficulties when it comes to establishing therapeutic processes. Although intensive searches for genetic markers have been carried out, methodological problems that arise in the definition of phenotypes, as well as in the selection of genetic techniques and the genes targeted for research, have meant that less progress has been made in these studies than was initially expected. Some of the aspects that have been advancing in recent years include clarification of the clinical phenotype to be studied, the analysis of clinical information to be used for the selection of the genetic sample and agreements about the genes the search is to be focused on. Today several genetic markers that are highly associated with the entity are known. CONCLUSIONS: We are very close to identifying specific genes, although this is only the first step towards understanding the underlying problem; how to use that information to benefit the patient is a challenge that researchers are currently facing. PMID- 17347944 TI - [Asperger's syndrome, little teachers: special skills]. AB - INTRODUCTION: Asperger's syndrome (AS) is characterised by its effects on reciprocal social interaction, verbal and non-verbal communication, difficulty in accepting changes, inflexible thinking and reduced fields of interest, but also by the presentation of special skills. DEVELOPMENT: On the occasion of the centenary of the birth of Hans Asperger, we briefly review the history of this researcher and offer a short description of the clinical features of the condition, including social interaction, communication, limited concerns and interests, routines and inflexibility, which are key points when it comes to reaching a diagnosis. Later, we also focus on Savant syndrome, which is a very common subgroup within AS and which is characterised by the patient's outstanding ability is certain special skills, such as hypermnesia, hyperlexia and hypercalculia, in mental feats concerning the perpetual calendar and in several branches of the arts, such as drawing, painting, sculpture and music. We discuss several famous cases of savants and explain some of the theories about its pathophysiology. CONCLUSIONS: Having special skills is a distinguishing mark of AS and identifying and facilitating them would provide us with a potential tool with which to accomplish suitable job opportunities. PMID- 17347945 TI - [Cognitive processing in autism spectrum disorders]. AB - INTRODUCTION: Autism involves a basic impairment in social cognition. Abnormalities in social behavior coexist with aberrant attention and deficient language. In the attentional domain, attention to people and socially relevant stimuli is impaired. Also children with autism spectrum disorders (ASD) are characterized by impairments in face recognition and decreased attention to faces. AIM: To review neurofunctional deficits underlying ASD by using event related potentials. CONCLUSIONS: Event related potentials demonstrate that auditory orienting deficits in autism cannot be explained by sensory deficits and that the orienting deficit in autism might be speech-sound specific, suggesting deficits particularly in social orienting. In addition, children with ASD have a disordered pattern of brain responses to faces and objects at an early age. PMID- 17347946 TI - [Asperger syndrome: diagnosis and treatment]. AB - INTRODUCTION AND DEVELOPMENT: Asperger syndrome is a pervasive developmental disorder characterized by social impairments, restricted interests, and repetitive behaviours. It is not associated with delay in language development as others pervasive developmental disorders. Diagnosis should be made based on a complete clinical history and psychological assessment; specific diagnostic instruments are useful. CONCLUSION: Asperger syndrome has no cure, but clinical features and those secondary to comorbid conditions could improve with an early diagnosis and correct individualized interventions. PMID- 17347947 TI - [The influence of the social perception of emotions in the formal language of children with Asperger's syndrome or high-functioning autism]. AB - INTRODUCTION: People with Asperger's syndrome or high-functioning autism both have difficulties in the social area that become manifest in alterations affecting the development of mental skills, difficulties in self-perception and control over the emotions, and scant success when it comes to developing social interactions that last for any length of time. DEVELOPMENT: A linguistic analysis of the answers children give when asked to talk about personal events in which they made someone angry or somebody made them angry reveals the intention to generate empathy and sympathy in children who have undergone normal development. These two tasks were performed by children with Asperger's syndrome or high functioning autism and the results were then analysed. CONCLUSIONS: Competencies of an emotional nature, which were detected through the language used, vary widely among children with Asperger's syndrome and high-functioning autism of the same chronological age and indicate a motivation to generate a positive representation of themselves in their interlocutor when they answer questions in which they have to talk about negative events they were involved in. PMID- 17347948 TI - [Interactive formats and executive functions in early development]. AB - INTRODUCTION: Cognitive control improve planning, action selection to get a goal (flexibly) and their modifiability. Executive functions are a functional construct related with solving process and goal maintenance. AIM: Among executive functions we will study the resistance of interference, stopping irrelevant information and the inhibition of a dominant but inapropiate scheme as well as the influence of the type of tutoring during action execution. SUBJECTS AND METHODS: We studied 15 infants with alternative courses of development (typical babies and Down' syndrome babies) at a developmental level equivalent to 15 months old, and 6 months later. Infant' spontaneous activity is videotaped longitudinally for a 15 minutes period, activity units are codified by a mixed system of categories and quantified in order to know the significative differences on tutoring types, their dynamic an effects associated with infant's executive functions. RESULTS: a) Adult's directive tutoring is more frequent with Down's syndrome babies than with typical babies; b) Directive tutoring is less adjusted and produces more interferences; c) There is a differential capacity to interference resistance, less present in the Down's syndrome babies; d) Executive functioning shows developmental and differential trends. CONCLUSIONS: If development is individual and socially influenced, the individual differential efficacy of executive functions and the type of tutoring contributes to typical or atypical developmental course. Educational and health consequences are proposed. PMID- 17347949 TI - [Borderline intellectual capacity and executive dysfunction]. AB - INTRODUCTION: Borderline intellectual capacity (BIC) is defined by the detection of an intelligence quotient of between 71 and 84. In most cases, the diagnosis of BIC only represents the appreciation of one characteristic measured by intelligence tests. Thus, in most patients with BIC there is an underlying disorder that has helped to configure an intelligence quotient within the borderline range. The executive functions themselves, in addition to playing a role in the cognitive foundations of the disorders associated with BIC, also exert an effect on the degree of intelligence. AIM: To evaluate the impact of executive dysfunction in a group of patients with BIC. PATIENTS AND METHODS: A group of 87 patients who had been diagnosed with BIC were selected and their clinical diagnoses were analysed. The scores from the BRIEF questionnaire for evaluating the executive functions were obtained for 51 of the patients. These results were compared with those from a sample of patients with attention deficit hyperactivity disorder (ADHD). RESULTS: Prevalence of neurocognitive disorders (ADHD, learning difficulties and pervasive developmental disorders) was high in the group of patients. Moreover, an important degree of executive function involvement was also observed. CONCLUSIONS: Neurodevelopmental disorders, and more particularly ADHD, exert a strong influence on intellectual capacity. Early detection and intervention in those disorders may prevent many cases of BIC by lessening the sustained impact of a poor working memory. PMID- 17347950 TI - [The effects of protein-energy malnutrition on the central nervous system in children]. AB - INTRODUCTION: Protein-energy malnutrition continues to affect millions of human beings in developing countries. Children suffer most from the shortage of nutrients because at early ages malnutrition has an important impact on the central nervous system. The changes that malnutrition triggers in the brains of these children will have severe consequences on their development and learning abilities. DEVELOPMENT: Reports of important alterations in the head circumference and brain growth of malnourished children have been published in the literature, together with accounts of changes in both the dendritic arborisation and the morphology of the dendritic spines, as well as in myelination. Computerised tomography brain scans and magnetic resonance imaging in children suffering from malnutrition show images that are compatible with cerebral atrophy. The lack of environmental stimulation associated with malnutrition worsens the damage to the central nervous system. All the alterations that are observed in such cases give rise to important compromise of the child's higher brain functions, which may well lead to permanent neuropsychological damage. CONCLUSIONS: Protein-energy malnutrition produces notable morphological changes in the brains of children in the developing world. These changes damage the intellectual potential of those who survive and limit their capacity to become part of the competitive world. Paediatric neurologists working in these areas of the world must make greater efforts to disseminate this problem and to make public institutions aware of the issue so that they do not desist in the fight against child malnutrition. PMID- 17347951 TI - [Resilience and risk in children with learning disabilities]. AB - AIM: To stress the desirability of considering the resilience approach as a complement to the risk approach in the study and intervention of children with learning disabilities (LD). DEVELOPMENT: Most of the research carried out into LD has used the correlational methodology, which has given rise to chance inferences being made and to considering them as being a risk factor for development in their own right. Yet, the findings from more recent longitudinal studies make it necessary to reconsider the inevitability of negative results in the development of children with LD and to identify the processes and the factors underlying successful development, i.e. personal and social skills (self-efficiency, emotional coping, effective use of help, discrete view of difficulty, unconditional acceptance and support, and so on). CONCLUSIONS: The resilience approach is not an alternative that excludes the risk approach, but rather they complement each other and are both necessary in order to gain an understanding of LD and intervention. Optimising the development of individuals with LD is a task that can be made easier by assuming that resilience is a capacity that is present in all individuals and can also be improved. PMID- 17347952 TI - [Corticosteroid treatment for a first episode of steroid-sensitive nephrotic syndrome (SSNS) in children: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of the use of corticosteroid treatment for a first episode of steroid-sensitive nephrotic syndrome (SSNS) in children is presented. METHODS: SR of RCT and RCT on SSNS therapeutic interventions were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Results. One SR including 15 RCT was available on this topic. Methodological quality of available RCT was suboptimal according to current methodological standards. RESULTS: In children with a first episode of SSNS, corticosteroids administered for 3 months or more compared with 2 months' administration are associated with a significant reduction in the risk of relapse at 6, 12 and 24 months, and in frequent relapsing rates, even though complications did not seem significantly increased (psychological, ocular, gastrointestinal disorders, hypertension, growth delay, Cushingoid syndrome, infection and osteoporosis) (evidence from SR). 6-month compared to 3-month treatment regimens are associated with a significant reduction in the risk of relapse at 12-24 months (evidence from SR). Increasing steroids cumulative doses are associated with increasing improvements in the risk of relapse (evidence from RCT). The risk of relapse at 12-24 months correlates inversely with duration of treatment (evidence from SR). CONCLUSION: In SSNS children, current available evidence supports the hypothesis that primary intervention should be a high dose of corticosteroids administered for 3 months or more. Further studies are necessary to test this hypothesis in adult patients. PMID- 17347953 TI - [Therapeutic strategies for membranous nephropathy: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of interventions for idiopathic membranous nephropathy (MN) is presented. METHODS: SR of RCT and RCT on interventions for MN were identified referring to a Cochrane Library and Renal Health Library search (2005 update). RESULTS: Three SR and 18 RCT were available to address this issue. Methodological quality of available RCT was suboptimal according to current methodological standards. In patients with MN, nephrotic syndrome and normal renal function, methylprednisolone and chlorambucil or cyclophosphamide for 6 months alternately increase the probability of nephritic syndrome remission (evidence from SR) and long-term renal protection (evidence from RCT). Other drugs (ACTH and cyclosporine) are associated with nephrotic syndrome remission, but there is no evidence of significant effects on renal function (evidence from RCT). In patients with impaired renal function, association of corticosteroids and cytotoxic agents is proven to cause a short-term delay of renal damage progression, even though benefits are counterbalanced by complications (evidence from RCT). CONCLUSION: In patients with MN, nephrotic syndrome and normal renal function, current available evidence supports the hypothesis that primary intervention should be the association of corticosteroids and cytotoxic agents. Secondary therapeutic choices include ACTH and cyclosporine. Further studies are necessary to test new immunosuppressive agents such as mycophenolate mofetil. PMID- 17347954 TI - [Immunosuppressive and non-immunosuppressive agents for patients with IgA nephropathy: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of the use of immunosuppressive and non immunosuppressive treatments in IgA nephropathy (IgAN) is presented. METHODS: SR of RCT and RCT on treatment in patients with IgAN were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: Two SR of RCT (13 and 3 RCT, respectively), and 18 further RCT were available to address this issue. Methodological quality of available trials was suboptimal. In patients with IgAN and normal or mildly impaired renal function, steroids significantly delay the progression to end stage kidney disease (evidence from SR) and improve proteinuria. Associating steroids and cytotoxic agents (cyclophosphamide followed by oral azathioprine) proves effective in patients with rapidly progressive renal disease (evidence from RCT). Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers significantly improve proteinuria (evidence from RCT), but there are no conclusive data on efficacy on hard patient level endpoints. There are no conclusive data available on the use of a therapy combining these agents. CONCLUSION: In IgAN patients current evidence supports the hypothesis that immunosuppressive agents delay the progression to end stage renal disease. Further studies are necessary to test this hypothesis in selected patient populations. PMID- 17347955 TI - [Treating lupus nephritis: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of lupus nephritis (LN) treatment is presented. METHODS: SR of RCT and RCT on different therapeutic options for LN were identified referring to a Cochrane Library and Renal Health Library search (2005 update). RESULTS: One SR of 25 RCT and 6 further RCT were available to address this issue. Methodological quality of available RCT was suboptimal according to current methodological standards. In LN patients, combining cyclophosphamide (CyA) and steroids as induction therapy results in a reduced risk of serum creatinine doubling compared to steroids alone, although there is no evidence of significant survival advantage and risk of ovarian failure was demonstrated (evidence from SR). The association of azathioprine (Aza) and steroids significantly reduces the risk of all-cause mortality compared to steroids alone (evidence from SR). No significant survival advantages from the association of plasma exchange and CyA or Aza are proven (evidence from SR). No significant differences on renal and survival endpoints are demonstrated with different dosing of CyA (evidence from RCT). CONCLUSION: In LN patients available evidence supports the hypothesis that immunosuppressive agents reduce the risk of all-cause mortality and the risk of progressive renal disease. Further studies are necessary to test new immunosuppressive agents such as mycophenolate mofetil in severe LN patients. PMID- 17347956 TI - [Antihypertensive agents for the prevention of chronic kidney disease progression: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of the use of antihypertensive agents to prevent chronic kidney disease progression (CKD) is presented. METHODS: SR of RCT and RCT on antihypertensive agents used to prevent CKD progression were identified referring to a Cochrane Library and Renal Health Library search (2005 update). RESULTS: Seven SR and 26 further RCT were found addressing this intervention issue. Methodological quality of available RCT was suboptimal according to current methodological standards. Angiotensin converting enzyme inhibitors (ACE-I) are associated with significant effects on the prevention of CKD progression in non-diabetic and diabetic patients (evidence from SR). Angiotensin receptor blockers (ARB) are as effective as ACE-I in delaying CKD progression in diabetic and non-diabetic patients (evidence from SR). Dihydropyridine and non-dihydropyridine calcium antagonists have not been found to significantly affect proteinuria and CKD progression (evidence from SR). Combination therapy with ACE-I and ARB is associated with a significant reduction in the risk of CKD progression and proteinuria, but long term data are only available in patients with non-diabetic nephropathy (evidence from RCT). CONCLUSION: Available evidence of renal protection suggest that ACE-I and ARB should be recommended in CKD patients (diabetic and non-diabetic nephropathy). Further studies are necessary to test the effectiveness of other antihypertensive agents or combination therapy. PMID- 17347957 TI - [Use of statins for preventing cardiovascular and renal outcomes in patients with chronic kidney disease excluding dialysis: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of the efficacy of statins in chronic kidney disease patients (CKD, non-dialysis patients) is presented. METHODS: SR of RCT and RCT on statins in CKD (non-dialysis) patients were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: Three SR and 36 RCT were found addressing this intervention issue. Methodological quality of the relevant RCT was suboptimal. There is no enough evidence to suggest that statins are associated with a significant reduction in the risk of serum creatinine doubling or of end-stage renal disease in CKD patients (evidence from SR and RCT). Statins compared to placebo or no treatment are associated with significant improvements in proteinuria (evidence from SR). Statins are also associated with significant reduction in the risk of cardiovascular events and mortality in CKD patients (evidence from SR and RCT) and in renal transplant recipients (evidence from RCT), and no significant increases in the risk of rhabdomyolysis and hepatotoxicity in CKD patients. CONCLUSION: Available evidence supports the hypothesis that statins should be recommended in CKD patients (non dialysis patients) on the basis of significant evidence of cardiac and renal protection and no evidence of significant harms. Further studies are necessary to test this hypothesis in selected patient populations. PMID- 17347958 TI - [Erythropoietins and haemoglobin targets to prevent the progression of chronic kidney disease: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of Systematic Reviews (SR) of Randomized Trials (RCT) or RCT data only. The present guideline reports evidence of the use of Erythropoietins (EPO) and/or optimal haemoglobin (Hgb) targets to delay Chronic Kidney Disease (CKD) progression. METHODS: SR of RCT and RCT on EPO and different Hgb targets in CKD (pre-dialysis) were identified searching in the Cochrane Library and Renal Health Library (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: Two SR (15 RCT) and 5 further RCT were found addressing the intervention issue. No significant evidence supporting the use of EPO compared with placebo/no treatment to prevent or delay CKD progression was found (evidence from SR). Progression rates do not appear to be affected by Hgb targets (evidence from SR). Methodological quality of included RCT was suboptimal. In diabetic patients not receiving renin-angiotensin-system inhibitors, early EPO treatment (when Hgb >=9 g/dL) with target Hgb >=13 g/dL as compared to delayed treatment initiation (Hgb < 9 g/dL) is associated with reduced risk of disease progression, end-stage renal disease and death (evidence from RCT). CONCLUSION: In CKD patients not undergoing dialysis current evidence does not support the hypothesis that EPO treatment or optimal Hgb targets reduce the progression rate of the disease. Further studies are necessary to test this hypothesis in selected patient populations. PMID- 17347959 TI - [Haemoglobin targets for chronic kidney disease: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of optimal haemoglobin (Hb) target levels in chronic kidney disease (CKD), either for pre-dialysis, dialysis or renal transplanted patients, is presented. METHODS: SR of RCT and RCT on different Hb target levels in patients with CKD were identified, referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: Four SR (19 RCT) were found addressing the point. Methodological quality of available trials was suboptimal. In CKD patients (non-dialysis patients) Hb targets of 11.3 g/dL should be preferred to Hb >13.5 g/dL (evidence from RCT). A Hb target of 11.0 11.5 g/dL should be preferred in CKD patients receiving dialysis treatment without significant cardiac disease, since no survival benefits has been showed with Hb >14 g/dL (evidence from RCT). The optimal Hb target in haemodialysis patients with severe cardiac disease should be 10.0-10.5 g/dL (evidence from SR). Increases in Hb target lev-els are associated with improved quality of life, although this was mainly noticed in observational studies and in few RCT often relying on unvalidated quality of life assessment scales. CONCLUSION: In CKD patients current available evidence supports the hypothesis that optimal Hb targets should be low to subnormal. PMID- 17347960 TI - [Calcimimetics, phosphate binders, vitamin D and its analogues for treating secondary hyperparathyroidism in chronic kidney disease: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of the use of calcimimetics, phosphate binders, vitamin D and vitamin D analogues for treating secondary hyperparathyroidism in chronic kidney disease (CKD) is presented. METHODS: SR of RCT and RCT on interventions for secondary hyperparathyroidism in CKD were identified referring to a Cochrane Library and Renal Health Library search (2005 update). RESULTS: Three SR and 8 RCT were found addressing this intervention issue. Methodological quality of available RCT was suboptimal according to current methodological standards. Calcimimetics used in patients receiving haemodialysis or peritoneal dialysis are more effective than placebo in controlling secondary hyperparathyroidism (reduced parathyroid hormone levels, calcium levels and phosphorus levels). All phosphate binders are effective in controlling hyperphosphatemia but different doses are to be used with different agents to achieve similar targets. Dosing needs to be adjusted according to phosphorus levels. Vitamin D and its analogues are recommended in CKD patients, although there is no significant evidence of superiority of individual agents in head-to-head comparisons. Dosing should be based on baseline parathyroid hormone levels, but the risk of hypercalcemia should also be considered. CONCLUSION: Available evidence suggests that calcimimetics, phosphate binders and vitamin D or its analogues are effective in the treatment of secondary hyperparathyroidism. Superiority of individual agents or doses is still deeply debated. Further studies are necessary to test these issues. PMID- 17347961 TI - [Antimicrobial agents for preventing peritonitis in peritoneal dialysis: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. The present guideline reports evidence of the use of antimicrobial agents for preventing peritonitis in peritoneal dialysis (PD). METHODS: SR of RCT and RCT on treatments aiming at preventing peritoneal dialysis peritonitis were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: One SR and 19 RCT were found addressing this issue. Staphylococcus Aureus nasal carriage treatment with mupirocin reduces exit-site and tunnel infections but not peritonitis. Topical gentamicin treatment on the exit site reduces Staphylococcus Aureus infection and peritonitis incidence. Intravenous antibiotics administration prior to catheter placement significantly reduces the risk of early peritonitis but not exit-site and tunnel infections. Oral nistatin associated with antibiotic treatment significantly reduces the incidence of Candida peritonitis. No other prophylaxis measure seems to be effective based on available evidence. CONCLUSION: In patients on peritoneal dialysis current evidence supports the hypothesis that topical mupirocin reduces the risk of Staphylococcus Aureus peritonitis, intravenous antibiotics prior to catheter placement prevent the risk of early peritonitis, and oral nistatin reduces the risk of Candida peritonitis. Further studies are necessary to test the effectiveness of other interventions. PMID- 17347962 TI - [Catheter-related interventions to prevent peritonitis in peritoneal dialysis: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. The present guideline report evidence of catheter-related interventions to prevent peritonitis in peritoneal dialysis (PD). METHODS: SR of RCT and RCT of catheter-related interventions to prevent peritonitis in PD were identified referring to a Cochrane Library and Renal Health Library search (2005 update). RESULTS: Two SR and 17 RCT were found addressing this issue. Methodological quality of available RCT was suboptimal according to current methodological standards. The use of the Y-set systems with disinfectant and the twin-bag systems was associated with a significantly lower risk of peritonitis. No other catheter-related interventions were found to be of proven efficacy in preventing the risk of peritonitis and exit-site/tunnel infection in PD patients. CONCLUSION: It is still unknown whether any particular PD catheter design or implantation technique are effective to prevent peritonitis in patients on peritoneal dialysis. Further studies are necessary to test the effectiveness of new interventions. PMID- 17347963 TI - [Antiviral prophylaxis and pre-emptive therapy for the prevention of Cytomegalovirus infection in renal transplant recipients: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of antiviral prophylaxis and pre-emptive treatment for preventing cytomegalovirus (CMV) infection in kidney transplant recipients is presented. METHODS: SR of RCT and RCT on antiviral prophylaxis and pre-emptive treatment for CMV infection in kidney transplant recipients were identified referring to a Cochrane Library and Renal Health Library search (2005 update). RESULTS: Evidence from 4 SR of RCT was gathered to address this issue. Methodological quality of available RCT included in these SR was suboptimal. Antiviral prophylaxis is associated with a significant reduction in the risk of CMV infection and all-cause mortality in CMV-negative and CMV-positive renal transplant recipients from CMV-positive donors, regard-less of the immunosuppressive treatments used (evidence from SR). Pre-emptive therapy has been found to be effective in preventing CMV disease but not all-cause mortality in these patients, even if evidence is less satisfactory compared to data on antiviral prophylaxis (evidence from SR). There is insufficient evidence of conclusive recommendations on treatment of CMV-negative recipients of renal transplants from CMV-negative donors. CONCLUSION: In kidney transplant patients current available evidence supports the hypothesis that antiviral prophylaxis and pre-emptive therapy are effective in preventing CMV disease; but antiviral should be the treatment of choice. Further studies are necessary on the treatment of CMV negative recipients from CMV-negative donors. PMID- 17347964 TI - [Treating peritonitis in peritoneal dialysis: guideline from the Italian Society of Nephrology]. AB - BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. The present guideline reports evidence of interventions to treat peritonitis in peritoneal dialysis (PD). METHODS: SR of RCT and RCT on treatments for peritoneal dialysis peritonitis were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: Thirty-six RCT were found addressing the intervention issue. Vancomycin or first generation cephalosporins may be used for treating peritoneal dialysis peritonitis due to Gram-positive agents. Third-generation cephalosporins or amino-glycosides may be used for Gram negative agents peritonitis. Association of first-generation cephalosporins and agents against Gram-negative bacteria via the intraperitoneal route represents the most frequently used approach. Intraperitoneal administration of antibiotic agents is the most effective treatment of peritoneal dialysis peritonitis. Intermittent administration may be preferred to continuous administration of antibiotic agents in peritoneal dialysis peritonitis. CONCLUSION: In peritoneal dialysis peritonitis current evidence supports the hypothesis that intraperitoneal administration of antibiotics agents and intermittent administration may be preferred to other routes of administration and continuous administration. Further studies are necessary to test this hypothesis in selected patient populations. PMID- 17347966 TI - Management of secondary hyperparathyroidism in uremic patients: the role of the new vitamin D analogs. AB - Secondary hyperparathyroidism - a common comorbid condition in patients with chronic renal insufficiency - is considered a consequence of critical determinants such as hypocalcemia, phosphate retention and reduced levels of calcitriol production. In this complex mechanism, the skeletal apparatus and the nonskeletal targets such as vascular and heart valves are often involved, thus explaining the increased risk of cardiovascular morbidity and mortality of uremic patients. In this review we will focus on the major role played by Calcitriol deficiency as a trigger of secondary hyperparathyroidism and the crucial need for obiquitous vitamin D receptor activation in order to have an optimal PTH control and to obtain a modulation between inhibitors and inducers of soft tissue calcification. This review will also elucidate the possible role of paricalcitol a new vitamin D analog - in conditioning morbidity and mortality of patients on renal replacement therapy (RRT). PMID- 17347967 TI - Insulin resistance, metabolic syndrome and endothelial dysfunction. AB - The increasing prevalence of obesity and diabetes mellitus in most industrialized countries, including China and India, is reaching epidemic proportions and requires intense studies and interventions. Insulin resistance appears to be the most relevant feature of the metabolic syndrome and is often the precursor of diabetes mellitus. Insulin resistance has been associated with endothelial dysfunction, which is considered the initial step in the process of atherosclerosis. In this brief review, we analyze the relationship between insulin resistance, endothelial function and cardiovascular events. PMID- 17347968 TI - Acute renal failure in critically ill patients: indications for and choice of extracorporeal treatment. AB - The prescription of extracorporeal therapy for patients with acute renal failure involves many options: dialysis sessions may be intermittent or continuous, semicontinuous or slow-extended, with controversial indications still to be defined also depending on technical and logistic issues and related to the multidisciplinary cooperation needed in the management of critically ill patients. All efforts to evaluate extracorporeal treatments in these patients must be targeted not only towards supporting renal function, but towards all functional and metabolic derangements that can result from artificial blood purification, in any way achievable. PMID- 17347969 TI - Urinary tract infection: one lingering effect of childhood kidney diseases- review of the literature. AB - Urinary tract infection (UTI) is a possible warning sign of the presence of anomalies of the urinary tract. Following a UTI there is concern with recurrences which can contribute to scarring which may lead to hypertension, pregnancy induced hypertension and even renal failure in later years. Prospective studies using 99mTc-labeled dimercaptosuccinic acid (DMSA) have shown that 30%-40% of children will have renal scarring after febrile UTI, regardless of the presence or absence of vesicoureteral reflux (VUR). Many studies have demonstrated that VUR is an important risk factor for renal scarring after UTI. Hypertension affects at least 10% of children with renal scarring, and in adults with reflux nephropathy (RN), the prevalence of hypertension is also much higher (38%-50%). UTI, pregnancy-induced hypertension (PIH) or renal function deterioration alone or in some combination has been reported to be as high as 39% in women with renal scarring. RN is one of the important causes of end-stage renal disease (ESRD) worldwide. Prevention of renal scar development should reduce the incidence of hypertension in patients as they age. The appropriate management of childhood UTI includes education of parents, patients and general physicians to be sure that everyone is aware of not only the current condition, but also the possibility of future UTI-related situations. IN CONCLUSION: UTI itself is a warning sign of possible anomalies of the urinary tract, renal problems and/or chronic renal complications. Although VUR is primarily a disease of childhood, scarring from the disease can cause problems in later years, with the complicating factor that because only the renal scar remains, the VUR may be forgotten and not considered when diagnosing the current problem. PMID- 17347970 TI - AT1 receptors and the actin cytoskeleton during angiotensin II treatment. AB - BACKGROUND: The response of proximal convoluted tubules (PCTs) to angiotensin II is mediated by specific type 1 receptors found on both apical and basolateral surface membrane cells. After ligand association with type 1 receptors, different signaling pathways are triggered and determine changes in fluid absorption (Jv). The presence of AT1 and actin cytoskeleton, which are directly related to Jv, can undergo changes in distribution based on the actions of AngII and losartan. METHODS: Using a microperfusion technique and immunohistochemistry analysis, we investigated the basolateral action in PCTs, of AngII and/or losartan on Jv in rabbits, with regard to AT1 and actin cytoskeleton. RESULTS: AngII increased Jv, while in contrast, losartan and combined AngII + losartan led to its decrease. AngII did not change fluorescence intensity of AT1 receptors on tubular membranes, while losartan and AngII + losartan demonstrated a slight increase after treatment. On the other hand, AngII increased the fluorescence intensity of actin cytoskeleton, while losartan induced a decrease. AngII + losartan led actin cytoskeleton having a higher fluorescence intensity than in the control group. CONCLUSIONS: In the present study, we demonstrated that treatment of the basolateral side of PCT cells with AngII and losartan could lead to changes in absorptive tubular function. Important alterations were detected in AT1 receptor fluorescence on the luminal and basolateral membranes, and changes in F-actin cytoskeleton were verified by fluorescence following these protocols. PMID- 17347971 TI - A project to prevent renal diseases in the general population. AB - BACKGROUND: Early identification of subjects unaware of hypertension, diabetes and urinary abnormalities may prevent and/or reduce the onset and progression of kidney disease and ameliorate outcomes. In this study, the presence of hypertension, diabetes and urinary abnormalities was checked in subjects walking in a large square of Naples. METHODS: Data on age, habits and history of hypertension and/or diabetes were collected. Systolic and diastolic blood pressure were recorded. Protein, glucose, leukocytes and red blood cells were measured in urine. RESULTS: Participants numbered 698. Smoking (past or current smoking) was reported by 77%. Many of the participants with hypertension (35%) showed uncontrolled hypertension despite antihypertensive therapy. Hypertension was found for the first time in 154 subjects, and was confirmed in 28% of them afterwards; 23 participants (15% of hypertensive subjects) did not recheck blood pressure (BP) despite our summons. Proteinuria was found in 18% of new hypertensive participants. In 14 out of 17 diabetic participants without history of hypertension, hypertension was found for the first time and confirmed thereafter. Urinary abnormalities were present in more than one half of the participants, and were more prevalent in women and diabetics. Diabetics numbered 55 out of 698 subjects. In spite of therapy, glucosuria was present in almost one third of diabetics. Glucosuria was found in 6 participants with no history of diabetes (0.9% of all subjects). CONCLUSIONS: These data demonstrate that (a) many persons with hypertension are not aware of it; (b) control of hypertension is inadequate in most treated hypertensive patients and even worse in diabetics; (c) urinary abnormalities are frequently present in otherwise healthy subjects; (d) projects with the aim of raising awareness of hypertension, urinary abnormalities and diabetes in out-clinic subjects should be supported; (e) the use of a transportable clinic parked in residential areas of cities appears a suitable way for promoting evaluation of BP and urine test in subjects unaware of disease. PMID- 17347972 TI - Italian translation, cultural adaptation and validation of KDQOL-SF, version 1.3, in patients with severe renal failure. AB - BACKGROUND: This study aims to confirm the reliability and validity of the KDQOL SF in its Italian version. Cultural adaptation of such an instrument to assess quality of life of patients with chronic kidney disease is a major challenge. METHODS: The instrument was translated according to the translation algorithm. A trained psychologist administered the KDQOL-SF to 188 patients. RESULTS: Completeness was optimal. Item internal consistency was satisfied for 74.5% and 87.5% of patients for the kidney and generic part, respectively. Discriminant validity was satisfied for 96.3% and 98.6% of patients. Cronbach's alpha coefficient was >70% in 70% and 75% of patients. While assessing the responsiveness (external discriminating validity) of KDQOL-SF, we found lower scores (worse functioning and well-being) in females, patients aged 65 years or older, with low hemoglobin, hematocrit and high Kt/V, and in patients with a diagnosis of amyloidosis. Moreover, the score for physical health was lower in the absence of dialytic treatment and with a longer history of dialysis. The score for mental health was lower for lower creatinine levels and for a shorter dialytic history. The disease targeted score was lower in the absence of dialytic treatment, and the score for patient satisfaction was lower in the presence of dialytic treatment and for a longer dialytic history. CONCLUSIONS: The Italian translation of KDQOL-SF sounds natural, is easy to understand and reduces possible cultural biases to a minimum. A field test gave results comparable to other international validations, supporting the use of KDQOL-SF in cross-national surveys (for the Pavia Working Group on QoL in Organ Transplant). PMID- 17347973 TI - Efficacy of single dose of oral mizoribine pulse therapy two times per week for frequently relapsing nephrotic syndrome. AB - We assessed the efficacy of a single dose of oral mizoribine (MZB) pulse therapy two times per week for children with frequently relapsing nephrotic syndrome (FRNS). Eleven children with FRNS in remission were treated with oral MZB pulse therapy (daily dose 6 mg/kg; maximum total dose 300 mg). We compared their clinical manifestations before and after oral MZB pulse therapy and examined the changes in serum MZB concentration in each patient on the days when MZB was administered. Eight patients had no subsequent relapses (responders), and prednisolone could be discontinued. Although 2 of the other 3 patients (nonresponders) had one relapse and the remaining patient had two relapses, both the dosages of prednisolone and frequency of relapse after oral MZB pulse therapy were significantly lower than before oral MZB pulse therapy. The peak blood concentration and AUC0-4 of MZB in the responders were higher than in the nonresponders. None of patients had severe adverse effects, such as uricacidemia, leukopenia, liver dysfunction or alopecia. Oral mizoribine pulse therapy consisting of a single dose two days a week may be effective and safe in some FRNS patients. PMID- 17347974 TI - Ramipril in post-renal transplant erythrocytosis. AB - BACKGROUND: Posttransplant erythrocytosis (PTE; i.e., hematocrit [Ht] >=51%) may be responsible for cardiovascular events. Angiotensin-converting enzyme inhibitors (ACEIs) are increasingly employed in PTE treatment. Diverse ACEIs have been administered at variable doses and with erratic follow-up. In addition, guidelines recommend the administration of ACEIs as first-line therapy for PTE but do not give information on dosage. In this study the dose-response of a single ACEI was assessed, and patients were followed up for 1 year. The role of ACE gene polymorphism in both prevalence of PTE and successful response to ACEI therapy was also tested. METHODS: At study entry, blood chemistry and ACE-gene polymorphism were measured. ACEI (ramipril) was initiated at 1.25 mg/day; if Ht was still >=51%, ramipril was increased every 6 weeks to ensuing greater dosages. Scheduled dosages were 1.25, 2.5, 5.0, 7.5 and 10 mg/day. Blood chemistry was repeated every 6 weeks. Serum erythropoietin (EPO) concentration was assayed at the start and end of the study. Follow-up was extended for 1 year. RESULTS: PTE developed 12.6 +/- 16.0 months after transplantation in 40 out of 400 patients; 27 patients completed the study. Initial Ht was not correlated with any variable. Final Ht appeared normalized in 26 out of 27 patients. Mean dose (+/- SD) of ramipril was 4.6 +/- 3.6 mg. Mean time for correction of PTE was 135 days, and was not dependent on baseline Ht, hemoglobin or EPO. PTE relapsed in 4 patients. Prevalence of PTE and successful response to ramipril was not dependent on ACE gene polymorphism. CONCLUSION: Ramipril was effective in PTE; low doses normalized Ht in most patients. No clinical characteristics or biochemical variables predicted the response to ramipril. PTE may relapse; thus long-term follow-up is mandatory. PMID- 17347975 TI - L-Propionyl carnitine, homocysteine and S-adenosylhomocysteine in hemodialysis. AB - BACKGROUND: L-Carnitine, the acyl carrier into mitochondria, is derived from trimethyllysine. The formation of the latter compound is catalyzed by an S adenosylmethionine methyltransferase, yielding S-adenosylhomocysteine (AdoHcy), the homocysteine direct precursor, as a product. Aim of this work was to determine if exogenously administered L-propionyl carnitine affects plasma levels of homocysteine, a cardiovascular risk factor, and its active metabolite AdoHcy, in chronic renal failure patients on hemodialysis. METHODS: Plasma homocysteine and AdoHcy were determined by means of HPLC separation and detection in 14 hemodialysis patients before and after two months of i.v. L-propionyl carnitine treatment. RESULTS: No significant differences were observed in plasma concentrations of homocysteine or AdoHcy after therapy. CONCLUSIONS: Treatment with a carnitine derivative does not significantly influence the plasma concentrations of homocysteine or of its active metabolite, AdoHcy, which are involved as risk factors for cardiovascular disease in chronic hemodialysis patients. PMID- 17347976 TI - Vascular changes in chronic renal disease patients with secondary hyperparathyroidism. AB - BACKGROUND: Secondary hyperparathyroidism (SHPT) and its metabolic consequences - high serum phosphate and calcium x phosphate (Ca x P) product - are associated with cardiovascular disease in chronic kidney disease (CKD). We evaluated the relationship between PTH, mineral metabolism, vascular reactivity and arterial stiffness in patients with CKD. METHODS: The study included 31 CKD patients and 12 matched controls. Brachial artery diameter was recorded at baseline and after reactive hyperemia (flow-mediated vasodilation) and 0.45 mg of trinitrate, to analyze the flow-dependent and flow-independent responses. Large vessel stiffness was evaluated on the common carotid artery. RESULTS: Compared with controls, both flow-mediated (5.8% +/- 4.3% vs. 11.6% +/- 5.4%; p<0.001) and flow-independent (11.7% +/- 7.6% versus 23% +/- 7.5%; p<0.001) vasodilation were reduced in CKD. Flow-mediated vasodilation was negatively correlated with PTH (r=-0.416, p<0.05) and age (r=-0.365, p<0.05) and positively with flow-independent vasodilation (r=0.483, p<0.01). Blood pressure, dialysis duration, hematocrit and serum levels of Ca, P, and Ca x P product, lipids, and medications did not influence flow mediated function. Carotid distension correlated independently and negatively with age (r=-0.681, p<0.01) and Ca x P product (r=-0.496, p<0.01) but was not influenced by PTH. CONCLUSION: In CKD, PTH adversely affects vascular reactivity, possibly by interfering with endothelial function, while large vessel distension is influenced by Ca x P product but not by PTH. This result suggests a dual mechanism of vascular aggression in SHPT: an endothelial effect mediated by PTH and a media/adventitial effect linked to alterations in mineral metabolism. PMID- 17347977 TI - Long-term intravenous epoetin-alpha / darbepoetin-alpha ratio in iron-replete hemodialysis patients. AB - BACKGROUND: Equivalence of intravenous (i.v.) and subcutaneous (s.c.) dosage requirements is a notable characteristic of darbepoetin-alpha (DPO), as opposed to other epoetins (EPOs). Currently in Europe, the EPOs/DPO conversion factor (200 IU EPOs = 1 microg DPO) does not take into account the route of drugs administration. To better define this ratio we have conducted a prospective, long term trial in a group of hemodialysis patients. SUBJECTS AND METHODS: At the start, we evaluated 40 iron-replete hemodialysis patients, but the final study was performed in the remaining 25 patients. During the first 6 months, patients were on i.v. epoetin-alpha (EPOalpha) maintenance therapy (phase 1: T-6 to T0). After conversion to i.v. DPO (initial 200:1 ratio) the observation was prolonged for a period of 12 months (phase 2: T0 to T12). DPO was administered at extended dose intervals and the EPOalpha/DPO rate was adjusted every month to maintain hemoglobin (Hgb) stability. Iron status and factors inhibiting erythropoiesis were continually checked to exclude unstable patients. RESULTS: Phase 1: EPOalpha weekly mean dose showed no significant variation. Phase 2: EPOalpha/DPO conversion factor progressively rose from 200 to 256.7 +/- 86.9 IU/microg at T7 (p<0.005) and 336.8 +/- 104.3 IU/microg at T12 (p<0.0005). DPO weekly mean dosage decreased from 40.0 +/- 12.0 microg/week at T0 to 31.6 +/- 3.7 microg/week at T7 (p<0.005) and 24.6 +/- 7.0 microg/week at T12 (p<0.0005). Mean weekly/patient acquisition cost of EPOalpha was euro 70.6 +/- 21.3 (T-6 to T0); after switching, the cost of DPO was euro 72.4 +/- 22.7 (T0) and fell to euro 53.1 +/- 11.2 during T6 to T12. CONCLUSIONS: The progressive increase of EPOalpha/DPO ratio demonstrated that i.v. DPO requires lower doses compared with i.v. EPOalpha. When drugs are administered i.v., the starting EPOalpha/DPO conversion factor should be increased over the 200:1 ratio, similar to recommendations outlined in the United States and Japan. DPO dose reduction translated to notable cost-savings. PMID- 17347978 TI - Infrapopliteal arterial revascularization for limb-threatening ischemia in patients with chronic kidney disease. AB - BACKGROUND: This study was undertaken to ascertain whether infrapopliteal arterial revascularization (IAR) for limb-threatening ischemia is worthwhile in patients with severe chronic kidney disease (CKD). METHODS: With prospectively entered data from a university teaching hospital's vascular registry, we reviewed the records of all patients with CKD who underwent IAR between January 1, 1990, and December 31, 2002. Primary, assisted primary and secondary patency rates, limb salvage, patient survival and amputation-free survival were assessed using Kaplan-Meier analysis. Factors influencing the outcome were evaluated with univariate and multivariate analyses. RESULTS: Eighty-seven consecutive patients underwent 93 IARs; more than half (53%) of the patients were diabetic and nearly all (84%) had foot tissue loss. No patients died during the perioperative (30 day) period. At 1 and 5 years, primary patency rates were 92.3% and 77.2% in the series as a whole, 89.5% and 71.4% for diabetics vs. 95.3% and 83.4% for nondiabetics (p=0.164), and 78.9% and 49.1% for patients on dialysis vs. 95.7% and 85.3% for those not on dialysis (p=0.006). At 1 and 5 years, the secondary patency rates were 93.4% and 85.6% in the series as a whole, 91.7% and 82.1% for diabetics vs. 95.3% and 88.7% for nondiabetics (p=0.381), and 84.2% and 68% for patients on dialysis vs. 95.7% and 90.1% for those not on dialysis (p=0.002). At 1 and 5 years, the limb salvage rates were 96.8% and 80.6% in the series as a whole, 98% and 71.4% for diabetics vs. 100% and 88.7% for nondiabetics (p=0.104), and 94.7% and 61.7% for patients on dialysis vs 97.3% and 85.9% for those not on dialysis (p=0.020). There were 31 late deaths in the series as a whole, with a 5 year survival rate of 62.5%. At 1 and 5 years, the amputation-free survival probabilities were 93.4% and 54.4% in the series as a whole, 91.7% and 38.6% for diabetics vs. 95.2% and 70.2% for nondiabetics (p=0.011), and 89.5% and 39% for patients on dialysis vs. 94.4% and 58.8% for those not on dialysis (p=0.097). The dialysis treatment was the only predictor of primary patency failure (p=0.04). CONCLUSIONS: Although the overall outcome was poorer in patients on dialysis, IARs for limb-threatening ischemia in patients with CKD can achieve satisfactory results in terms of graft patency, limb salvage and amputation-free survival, especially if the tissue loss is manageable and an adequate autologous conduit is available. PMID- 17347979 TI - Familial focal segmental glomerulosclerosis and retinitis pigmentosa: a new association. AB - The association of retinitis pigmentosa with renal disease is rare and occurs mainly in two conditions: medullary cystic disease and Bardet-Biedl syndrome; here we describe a case of retinitis pigmentosa with familial focal segmental glomerulosclerosis, which to the best of our knowledge has never been reported previously. PMID- 17347980 TI - Stevens-Johnson syndrome associated with oral minoxidil: a case report. AB - Minoxidil is frequently used in patients with advanced renal disease who have been unresponsive to other antihypertensive agents. We describe a case of a 50 year-old man with chronic renal failure who was hospitalized complaining of a 2 week history of sore throat that had progressed to severe oral lesions and multiple pustular blisters on many sites of his body. The patient had been placed on oral minoxidil for uncontrolled hypertension one week prior to the onset of symptoms. The diagnosis of minoxidil-induced Stevens-Johnson syndrome (SJS) was established, minoxidil was discontinued and the patient subsequently improved. Although minoxidil-induced SJS is extremely rare, clinicians should be aware of this potentially severe adverse effect. This report emphasizes the importance of monitoring patients who are taking oral minoxidil for any signs or symptoms associated with SJS. PMID- 17347981 TI - Urinalysis: do not forget this type of cell in renal transplantation. AB - Microscopic sediment analysis of urine from a 56-year-old woman who underwent renal transplantation showed many uncommon clusters of rounded and translucent cells containing globular mucous cytoplasmic inclusions (HPF, x400). These cells were bigger than leukocytes and, compared with uroepithelial cells, showed a smaller nucleus to cytoplasm ratio and appeared eosinophilic, being pink rather than azurophilic with Sternheimer-Malbin stain. They were also unlikely to be tubular cells, which are usually smaller, singly distributed and associated with dysmorphic erythrocytes and/or casts and/or a worsening in renal function. A review of the patient's history showed that a pretransplantation urologic surgical treatment, including ileal bladder reconstruction, had been performed. Intestinal epithelial cells should be remembered when examining urinary sediment. PMID- 17347982 TI - A rare case of postinfectious glomerulonephritis caused by pneumococcus in an adult patient. AB - Postinfectious glomerulonephritis (PIGN) is commonly seen as a complication of infection with nephritogenic strains of group A streptococci, mostly with Streptococcus pyogenes. Pneumococcal pneumonia leading to glomerulonephritis has been reported in the pediatric literature, but only one adult case has been previously reported. We are presenting a case of postinfectious glomerulonephritis caused by pneumococcal pneumonia in an adult. In the present case, other possible etiologies of nephritic syndrome were ruled out with negative antineutrophilic cytoplasmic antibody (ANCA), anti-glomerular basement membrane antibody (Anti-GBM), antistreptolysin O (ASO), antinuclear antibody (ANA), HIV and viral hepatitis profile. The low CH50 indicated a complement mediated injury. Renal biopsy was done showing immune complex-mediated crescentic glomerulonephritis consistent with postinfectious etiology. The patient received pulse dose steroids for 5 days followed by oral steroids. His urinary output improved along with normalization of his renal function, therefore dialysis was discontinued. We are presenting this case to alert clinicians to the possibility of postinfectious glomerulonephritis following pneumococcal pneumonia and to report the successful use of steroid therapy in such a situation. PMID- 17347983 TI - Homozygous factor V Leiden mutation and disseminated thrombosis in a patient with nephrotic syndrome. AB - We report the case of a young male patient with nephrotic syndrome and multiple venous thromboses. The patient presented various aggregated thrombophilic risk factors. He was found to be homozygous for factor V Leiden mutation and his anticardiolipin antibody and homocysteine levels were high. The association between nephrotic syndrome and venous thrombosis is well known. However the presence of disseminated thrombosis should prompt an intensive work-up for the detection of thrombotic risk factors and aggressive anticoagulant therapy. PMID- 17347984 TI - Hypomagnesemia and nephrocalcinosis in a patient with two heterozygous mutations in the CLDN16 gene. AB - We report the case of a 20-year-old male Caucasian patient with diagnosed nephrocalcinosis and a medical history of seizures and recurrent urinary tract infections. Laboratory investigations revealed clinical and biochemical abnormalities characteristic of familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Since FHHNC is caused by mutations in the CLDN16 gene encoding a renal tight junction protein, we sequenced the complete coding region of this gene and detected two heterozygous mutations, the known Leu151Phe (+453G- >T) mutation and a novel Cys120Arg (+358T-->C) mutation. Due to their location within the primary structure of Claudin-16, both mutations are suggested to interfere with renal paracellular magnesium conductance. PMID- 17347985 TI - An unusual cause of renal allograft dysfunction: graft papillary necrosis. AB - A 43-year-old nondiabetic man, 5 years post-renal transplantation, presented complaining of oliguria, fever and dysuria of 1-day duration. Graft ultrasound did not reveal any obstructive changes. Graft function did not improve in spite of 3 days of antibiotics. On the fourth day he passed fleshy material in urine subsequent to which his urine output improved and fever recovered. His graft function settled near to the previous baseline. Histological analysis of the material revealed necrosed renal papillary tissue. Renal papillary necrosis in allograft is uncommon and generally reported in the immediate postoperative phase, but it can still occur later in transplant follow-up. It is a potentially treatable cause for acute allograft dysfunction and should be suspected in transplant patients presenting with acute pyelonephritis but not getting relief from antibiotic therapy. PMID- 17347986 TI - Coinfection of cytomegalovirus and miliary tuberculosis in a post-renal transplant recipient. AB - Infections are the leading cause of morbidity and mortality during the early posttransplant period. Of these infections, pulmonary infections are the most serious. Bacteria are the leading pathogen, followed by various opportunistic pathogens, such as cytomegalovirus (CMV) and mycobacterium tuberculosis. This investigation describes a 52-year-old male with a rare coinfection of CMV pneumonitis and miliary tuberculosis, 2 months after renal transplantation. This is the first case report of a coinfection with cytomegalovirus and Mycobacterium tuberculosis presenting with diffuse pulmonary miliary lesions. PMID- 17347988 TI - The eating disorders medicine cabinet revisited: a clinician's guide to ipecac and laxatives. AB - OBJECTIVE: To describe the frequency of alternative medication use in bulimia nervosa (BN), and to review available nonprescription emetic (ipecac) and laxative products and their potential toxicities. METHOD: Survey data were collected from 39 consecutive treatment-seeking patients with BN or subthreshold BN. Survey data of the available nonprescription and herbal products from local retail stores were also collected. Toxicology information was reviewed on these agents from MEDLINE and herbal textbooks. RESULTS: Ipecac use occurred in 18% of the 39 patients. Laxatives had been used at some point to control weight or "get rid of food" by 67% of the patients. Of these, 31% had abused laxatives during the month prior to evaluation. In the product survey, 248 laxative-containing products were identified. CONCLUSION: There are numerous laxative products readily available to patients, and many of them have significant associated toxicities. Patients with BN tend to endorse high rates of laxative use. While ipecac is used infrequently, it can have deleterious consequences. Patients with BN should be screened for use of both ipecac and laxatives and should be educated about the potential consequences associated with the misuse of these agents. PMID- 17347989 TI - A new variant database for mismatch repair genes associated with Lynch syndrome. AB - Mutations in some mismatch repair (MMR) genes are associated with Lynch syndrome (LS; also called hereditary nonpolyposis colorectal cancer [HNPCC]), an autosomal dominant cancer susceptibility syndrome. Colorectal cancer (CRC) is the most frequent cancer observed in LS. However, tumors occur at a variety of extracolonic sites and individuals may have multiple primary cancers. LS is the most common hereditary form of CRC, accounting for approximately 1% of all CRC. Since the first account of mutations in MSH2 causing this cancer susceptibility syndrome in 1993, mutations in three additional MMR genes, MLH1, MSH6, and PMS2, have been shown to cause LS. More than 1,500 different variants have been identified in these four genes and approximately 80% of the alterations have been identified in MLH1 and MSH2. There have been a few previous attempts to systematically record MMR variants associated with LS patients; however, they were not complete nor were they continuously updated. Thus, it was our goal to generate and maintain a comprehensive catalogue of MMR variants from genes known to be mutated in LS (http://www.med.mun.ca/MMRvariants; last accessed 8 February 2007). Providing such a resource should aid investigators in understanding the significance of the variants. PMID- 17347990 TI - Dynamic MRI for imaging tumor microvasculature: comparison of susceptibility and relaxivity techniques in pelvic tumors. AB - PURPOSE: To assess the reproducibility of intrinsic relaxivity and both relaxivity- and susceptibility-based dynamic contrast enhanced (DCE) MRI in pelvic tumors; to correlate kinetic parameters obtained and to assess whether acute antivascular effects are seen in response to cisplatin- or taxane-based chemotherapy. MATERIALS AND METHODS: T1-weighted and T2*-weighted DCE-MRI and basal R2* measurements were performed on three consecutive days in women with gynecological tumors. The third scan was 21.0 (range 17.3-23.5) hours after the first cycle of chemotherapy. Kinetic parameter estimates were obtained and correlated between techniques. Test-retest reproducibility and response to treatment were assessed. RESULTS: Relative blood volume (rBV) and relative blood flow (rBF) correlated strongly with transfer constant (Ktrans), kep, and the initial area under the gadopentetate dimeglumine (Gd-DTPA) concentration-time curve (IAUGC) (all P<0.01). The group 95% confidence interval (CI) for change was -10.8 to +12.1%; +/-5.1%; -9.5 to +10.5%; +/-7.5%; for Ktrans, ve, kep, and IAUGC, respectively, and +/-13.6%, +/-2.4%, +/-11.6%, and +/-11.0%, for rBV, mean transit time (MTT), rBF, and R2*, respectively. There were no significant acute changes in kinetic parameter estimates in response to treatment on group analysis, apart from a small decrease in ve. CONCLUSION: The results confirm the dominant influence of flow on Ktrans in untreated gynecological tumors. There is no evidence of an acute, large magnitude antivascular effect caused by cisplatin- or taxane-based chemotherapy. PMID- 17347991 TI - Automated tissue segmentation and blind recovery of (1)H MRS imaging spectral patterns of normal and diseased human brain. AB - Constrained non-negative matrix factorization (cNMF) with iterative data selection is described and demonstrated as a data analysis method for fast and automatic recovery of biochemically meaningful and diagnostically specific spectral patterns of the human brain from (1)H MRS imaging ((1)H MRSI) data. To achieve this goal, cNMF decomposes in vivo multidimensional (1)H MRSI data into two non-negative matrices representing (a) the underlying tissue-specific spectral patterns and (b) the spatial distribution of the corresponding metabolite concentrations. Central to the proposed approach is automatic iterative data selection which uses prior knowledge about the spatial distribution of the spectra to remove voxels that are due to artifacts and undesired metabolites/tissues such as the strong lipid and water components. The automatic recovery of diagnostic spectral patterns is demonstrated for long-TE (1)H MRSI data on normal human brain, multiple sclerosis, and serial brain tumor. The results show the ability of cNMF with iterative data selection to automatically and simultaneously recover tissue-specific spectral patterns and achieve segmentation of normal and diseased human brain tissue, concomitant with simplification of information content. These features of cNMF, which permit rapid recovery, reduction and interpretation of the complex diagnostic information content of large multi-dimensional spectroscopic imaging data sets, have the potential to enhance the clinical utility of in vivo(1)H MRSI. PMID- 17347992 TI - Molecular imaging and therapy of atherosclerosis with targeted nanoparticles. AB - Advances in bionanotechnology are poised to impact the field of cardiovascular diagnosis and therapy for decades to come. This review seeks to illustrate selected examples of newly developed diagnostic and therapeutic nanosystems that have been evaluated in experimental atherosclerosis, thrombosis, and vascular biology. We review a variety of nanotechnologies that are capable of detecting early cardiovascular pathology, as well as associated imaging approaches and conjunctive strategies for site-targeted treatment with nanoparticle delivery systems. PMID- 17347993 TI - Assessment of human brain motion using CSPAMM. AB - PURPOSE: To quantify periodic displacement in the cranium using complementary spatial modulation of magnetization (CSPAMM) with harmonic phase (HARP) postprocessing. MATERIALS AND METHODS: CSPAMM tagging sequence with separate tag line preparation in two orthogonal directions was applied on 10 healthy volunteers in combination with HARP for tissue displacement mapping. RESULTS: Important features of brain dynamics, such as caudal displacement amplitude and the time-to-peak of the pulse wave were derived for six regions in the brain. Peak displacement values amounted to 0.18+/-0.02 mm, 0.10+/-0.01 mm, 0.09+/-0.02 mm, and 0.04+/-0.01 mm for regions in the pons, cerebellum, corpus callosum (splenium), and frontal lobe, respectively. Displacement values of the pons differed significantly from all other regions measured. With the additional information of the time-to-peak measure all six regions except the corpus callosum (splenium) and cerebellum can be distinguished. The values found suggest that the pulse wave travels from the brain stem first occipitally and then to the frontal lobe, where peak values appear later and are significantly attenuated. CONCLUSION: Direct quantification of periodic caudal brain tissue displacement is feasible with the proposed method, and several brain regions can be distinguished through peak displacement and time-to-peak values. PMID- 17347994 TI - Four-dimensional single breathhold magnetic resonance imaging using kt-BLAST enables reliable assessment of left- and right-ventricular volumes and mass. AB - PURPOSE: To prospectively determine the accuracy of four-dimensional (4D) kt broad-use linear acquisition speed-up technique (BLAST) accelerated MRI (kt BLAST) for the assessment of left-ventricular (LV) volumes and mass as well as right-ventricular (RV) volumes in comparison to standard multiple breathhold cine imaging. MATERIALS AND METHODS: A total of 40 patients with suspected or known coronary artery disease (CAD) underwent cardiac MRI. In each patient a standard multislice cine steady-state free precession (SSFP) sequence was performed with complete ventricular coverage during multiple breathholds. Additionally, a kt BLAST-accelerated 4D sequence with complete ventricular coverage was acquired during one single breathhold. For comparison of SSFP and kt-BLAST, the following LV parameters were determined: end-diastolic and end-systolic volumes, ejection fraction, end-diastolic diameter and mass. For comparison of RV dimensions, end diastolic and end-systolic volumes and ejection fraction were assessed. RESULTS: LV volumes, ejection fraction, diameter, and mass showed a strong correlation between SSFP and kt-BLAST (r=0.98-0.99; P<0.01). In addition, RV parameters demonstrated a high correlation (r=0.97-0.98; P<0.01). For all parameters, the calculated bias between both methods was found to be minimal (0.4-4%). CONCLUSION: 4D kt-BLAST-accelerated MRI enabled the accurate assessment of LV and RV quantitative parameters during one single breathhold when compared to standard multislice, multiple breathhold SSFP imaging. PMID- 17347995 TI - Measurement of liver fat content using selective saturation at 3.0 T. AB - PURPOSE: To validate an MRI technique for measuring liver fat content by calibrating MRI readings with liver phantoms and comparing MRI measurements in human subjects with estimates of liver fat content on liver biopsy specimens. MATERIALS AND METHODS: The MRI protocol consisted of fat and water imaging by selective saturation using a 3.0-T scanner. A water phantom and liver phantoms were scanned before each of 10 human subjects who underwent a liver biopsy to assess for nonalcoholic fatty liver disease (NAFLD). Liver fat content in human subjects was derived from a calibration curve generated by scanning the phantoms. Liver fat was also estimated by optical image analysis and pathologists' assessment of histologic sections. RESULTS: MRI measurements of the liver phantoms were highly reproducible. Measurements of liver fat content in human subjects made by MRI in two areas of the liver were strongly correlated (r=0.98, P<0.001). MRI measurements were highly associated with estimates of liver fat content made by optical image analysis (r=0.96, P<0.001) and with estimates made by the pathologists (r=0.93, P<0.001). CONCLUSION: We validated a technique for quantifying liver fat content based on selective fat and water imaging. The technique is accurate and reproducible and provides a noninvasive method to obtain serial measurements of liver fat content in human subjects. PMID- 17347996 TI - Dysregulation of X-linked gene expression in Klinefelter's syndrome and association with verbal cognition. AB - Klinefelter's Syndrome (KS) is a chromosomal karyotype with one or more extra X chromosomes. KS individuals often show language impairment and the phenotype might be due to overexpression of genes on the extra X chromosome(s). We profiled mRNA derived from lymphoblastoid cell lines from males with documented KS and control males using the Affymetrix U133P microarray platform. There were 129 differentially expressed genes (DEGs) in KS group compared with controls after Benjamini-Hochberg false discovery adjustment. The DEGs included 14 X chromosome genes which were significantly over-represented. The Y chromosome had zero DEGs. In exploratory analysis of gene expression-cognition relationships, 12 DEGs showed significant correlation of expression with measures of verbal cognition in KS. Overexpression of one pseudoautosomal gene, GTPBP6 (GTP binding protein 6, putative) was inversely correlated with verbal IQ (r = -0.86, P < 0.001) and four other measures of verbal ability. Overexpression of XIST was found in KS compared to XY controls suggesting that silencing of many genes on the X chromosome might occur in KS similar to XX females. The microarray findings for eight DEGs were validated by quantitative PCR. The 14 X chromosome DEGs were not differentially expressed in prior studies comparing female and male brains suggesting a dysregulation profile unique to KS. Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function. A screen of candidate genes may serve as biomarkers of KS for early diagnosis. PMID- 17347999 TI - In living color. PMID- 17347997 TI - Deletion of alpha-neurexins does not cause a major impairment of axonal pathfinding or synapse formation. AB - Alpha-neurexins are synaptic cell-surface molecules that are required for Ca(2+) triggered exocytosis. Mice lacking all three alpha-neurexins show drastically reduced neurotransmitter release at excitatory and inhibitory synapses and die early postnatally. Although previous histological analysis of newborn alpha neurexin triple mutants revealed only a moderate reduction in the density of type II synapses in the brainstem, cell culture studies proposed that neurexins are prominently involved in synapse formation. To assess the contribution of alpha neurexins to the formation and structural properties of synapses in vivo, we performed a detailed morphological analysis of the brains from surviving adult double knockout mice lacking two of the three alpha-neurexins. Despite their impaired neurotransmission, we did not observe any gross anatomical defects or changes in the distribution of synaptic proteins in adult mutants. Only mild structural alterations were found: a approximately 20% reduction of neuropil area in many brain regions, resulting predominantly from shortened distal dendritic branches and fewer spines, as demonstrated by Golgi impregnation of pyramidal neurons. Quantitative electron microscopy revealed ultrastructurally normal type I and II terminals and a approximately 30% decrease in the density of type II synapses in the neocortex. To exclude errors in pathfinding, we investigated axonal projections in the olfactory bulb of newborn knockouts and did not observe any changes. Therefore, alpha-neurexins are not essential for the formation of the vast majority of synapses in vivo but rather regulate the function of these synapses. PMID- 17348000 TI - Identification of the main arterial branches by whole-body contrast-enhanced MRA in elderly subjects using limited user interaction and fast marching. AB - PURPOSE: To extract a graph model corresponding to a predefined set of arterial branches from whole-body contrast-enhanced magnetic resonance angiography (CE MRA) data sets in elderly asymptomatic subjects, a high-incidence group. MATERIALS AND METHODS: Maximum intensity projections (MIPs) were used as an interface to place landmarks in the three-dimensional (3D) data sets. These landmarks were linked together using fast marching to form a graph model of the arterial tree. Only vessels of interest were identified. RESULTS: We tested our method on 10 subjects. We were able to build a graph model of the main arterial branches that performed well in the presence of vascular pathologies, such as stenosis and aneurysm. The results were rated by an experienced radiologist, with an overall success rate of 80%. CONCLUSION: We were able to extract chosen arterial branches in 3D whole-body CE-MRA images with a moderate amount of interaction using a single MIP projection. PMID- 17348001 TI - The developmental psychopathology of social anxiety in adolescents. AB - To evaluate a developmental psychopathology approach for understanding adolescent social anxiety, parent-reported predictors of social anxiety were examined in a nonclinical sample of adolescents. Structured diagnostic interviews were obtained from biological parents of 770 participants. Potential risk factors assessed included child characteristics: negative affect, shyness, separation anxiety disorder, and childhood chronic illness, as well as parent characteristics: major depression, panic disorder, and agoraphobia. Adolescent social anxiety was measured multiple times during high school. Findings indicate stability in social anxiety symptoms across time. Parent-reported, childhood negative affect, shyness, and chronic illness as well as parental panic disorder or agoraphobia were associated with adolescent social anxiety. Interactions were observed between parent-reported childhood shyness and gender and between parent-reported childhood shyness and parent-reported childhood chronic illness in the prediction of social anxiety. Parent-reported childhood shyness was a stronger predictor of adolescent social anxiety in females compared to males. The combined effect of subjects being positive for both parent-reported childhood shyness and parent reported childhood chronic illness was greater than would be expected based on additive effects. This study provides support for a multifactorial and developmentally informed understanding of adolescent social anxiety. PMID- 17348002 TI - Focal nodular hyperplasia: intraindividual comparison of dynamic gadobenate dimeglumine- and ferucarbotran-enhanced magnetic resonance imaging. AB - PURPOSE: To intraindividually compare the enhancement pattern of focal nodular hyperplasia (FNH) after dynamic administration of two bolus-injectable liver specific MR contrast agents, ferucarbotran and gadobenate dimeglumine. MATERIALS AND METHODS: A total of 19 patients with 24 FNHs underwent gadobenate dimeglumine and ferucarbotran-enhanced MRI during the hepatic arterial-dominant phase (HAP; 25 seconds), the portal-venous phase (PVP; 60 seconds), and the equilibrium phase (EP; 180 seconds). Hepatospecific phases were acquired on T1-weighted images 120 minutes after gadobenate dimeglumine administration, and on T2-weighted images 10 minutes after ferucarbotran administration. Lesion enhancement was independently analyzed by two observers. The kappa statistic was determined to evaluate the agreement between the enhancement patterns of the lesions. RESULTS: On gadobenate dimeglumine-enhanced MR images during HAP, PVP, and EP, FNHs were: hyperintense (24/20/13); isointense (0/4/11); and hypointense (0/0/0). On ferucarbotran enhanced MR images during HAP, PVP, and EP, FNHs were: hyperintense (2/0/0); isointense (16/9/14); and hypointense (6/15/10). Overall, poor agreement between both contrast agents was observed. During the hepatospecific phases, most (20/24; 83%) FNHs showed a typical enhancement pattern during the delayed hepatospecific phase. CONCLUSION: The dynamic enhancement pattern of FNHs is significantly different between gadobenate dimeglumine- and ferucarbotran-enhanced MRI. With respect to hepatospecific phase, the majority of FNHs showed a typical behavior on both contrast agents. PMID- 17348003 TI - Clustering, migration, and neurite formation of neural precursor cells in the adult rat hippocampus. AB - Adult neurogenesis occurs in the subgranular zone and innermost part of the dentate granule cell layer. To examine how neural precursor cells proliferate, migrate, and extend their neurites, we performed BrdU- and improved retrovirus green fluorescence protein (GFP)-labeling analyses. Soon after labeling the majority of BrdU+ cells and GFP+ cells expressed Ki67, a cell cycle marker, and formed clusters together with PSA+ neuroblasts. Most of the Ki67+ proliferating cells expressed Hu, an immature and mature neuronal marker, and the subpopulation expressed both Hu+ and GFAP+. In the clusters, Ki67+ and PSA+ cells strongly expressed beta-catenin and N-cadherin, but PSA+ cells outside the clusters did not. Therefore, it was mainly Hu+ neuronal precursor cells that proliferated within clusters in which the cluster cells are closely associated via cell adhesion molecules, such as N-cadherin/beta-cateninIn and PSA. The newly generated cells appeared to stay in the clusters for a few days and then disperse around the clusters. The findings of this in vivo analysis and in vitro time lapse imaging of early postnatal hippocampal slices support the notion that most postmitotic neuroblasts migrate tangentially from clusters, extending tangentially oriented processes, one of which often retains close contact with the clusters, and finally extend radial processes, or prospective apical dendrites. These results suggest that the clustering cells and tangentially migrating cells have a systematic cellular arrangement and intercellular interaction. PMID- 17348004 TI - Preparative chiral chromatography and chiroptical characterization of enantiomers of omeprazole and related benzimidazoles. AB - To chiroptically characterize the enantiomers of omeprazole and some structurally related benzimidazoles with circular dichroism (CD), preparative chiral liquid chromatography was utilized for the isolation of the pure enantiomers. A limited analytical column screen was performed identifying Kromasil-CHI-TBB and the amylose-based phases Chiralpak AD and AS as possible chiral stationary phases (CSPs) for the preparative scale separation of the enantiomers of the different benzimidazoles. Optimization of the chromatographic conditions with respect to retention, enantioseparation, and resolution was achieved by variation of the mobile phase constituents as well as of temperature. Because of the lability of the compound in slightly acidic media, supercritical fluid chromatography (SFC) could not be applied for a preparative scale separation of the enantiomers. The separation of omeprazole was optimized to give high throughput (2.6 kg racemate/kg CSP/day) and high enantiomeric excess of the obtained isomers. The absolute configurations of the pure enantiomers of rabeprazole, lansoprazole, and pantoprazole were determined from the strong correlation to the CD spectrum of (+)-(R)-omeprazole. For all the compounds, the (+)-enantiomers displayed similar chiroptical features as (+)-(R)-omeprazole and were thus assigned the (R)- configuration. Elution order of the optical isomers was monitored by injecting racemic solutions spiked with one of the isomers and also by an on-line laser polarimeter. Both the type of CSP and also the mobile phase constituents had a strong effect on elution order of the enantiomers. PMID- 17348005 TI - An unsuspected ecdysteroid/steroid phosphatase activity in the key T-cell regulator, Sts-1: surprising relationship to insect ecdysteroid phosphate phosphatase. AB - The insect enzyme ecdysteroid phosphate phosphatase (EPP) mobilizes active ecdysteroids from an inactive phosphorylated pool. Previously assigned to a novel class, it is shown here that it resides in the large histidine phosphatase superfamily related to cofactor-dependent phosphoglycerate mutase, a superfamily housing notably diverse catalytic activities. Molecular modeling reveals a plausible substrate-binding mode for EPP. Analysis of genomic and transcript data for a number of insect species shows that EPP may exist in both the single domain form previously characterized and in a longer, multidomain form. This latter form bears a quite unexpected relationship in sequence and domain architecture to vertebrate proteins, including Sts-1, characterized as a key regulator of T-cell activity. Long form Drosophila melanogaster EPP, human Sts-1, and a related protein from Caenorhabditis elegans have all been cloned, assayed, and shown to catalyse the hydrolysis of ecdysteroid and steroid phosphates. The surprising relationship described and explored here between EPP and Sts-1 has implications for our understanding of the function(s) of both. PMID- 17348006 TI - Methylselenol generated from selenomethionine by methioninase downregulates integrin expression and induces caspase-mediated apoptosis of B16F10 melanoma cells. AB - Melanoma is a highly metastatic cancer resistant to current chemotherapeutic and radiotherapeutic approaches. Several studies have shown that interactions between cancer cells and the extracellular matrix (ECM) are critical for the survival and invasion of metastatic cancer cells. In this study, we examine the effects of methylselenol generated from selenomethionine (SeMet) by methioninase (METase) on cell proliferation, adhesion, and expression of integrins in murine melanoma B16F10 cells, which are metastatic in the lungs of syngeneic C57BL/6J mice. Combined treatment with SeMet-METase decreased the expression of integrins alpha(4), beta(1), alpha(nu), and beta(3), and inhibited melanoma-ECM adhesion. Caspase-mediated apoptosis was induced following loss of cell adherence. Phosphorylation of focal adhesion kinase (FAK) and Akt, related to integrin mediated survival, were decreased upon treatment with SeMet-METase while phosphorylation of p38, PKC-delta, and IkappaBalpha increased. In the presence of specific inhibitors of p38, PKC-delta, and NF-kappaB, expression of integrins and cell adhesion to ECM were maintained and cell apoptosis was prevented in SeMet METase-treated melanoma cells. Treatment with caspase inhibitors restored cell viability and blocked poly (ADP-ribose) polymerase (PARP) cleavage, but did not restore integrin expression and cell adhesion to ECMs reduced by SeMet-METase. Based on these results, we propose that combined treatment with SeMet-METase induces caspase-mediated apoptosis in melanoma cells by altering integrin expression and adhesion. Furthermore, activation of p38, PKC-delta, and NF-kappaB is a prerequisite for the down-regulation of integrin expression, followed by detachment-mediated apoptosis. PMID- 17348007 TI - Eph receptor expression defines midline boundaries for ephrin-positive migratory neurons in the enteric nervous system of Manduca sexta. AB - Eph receptor tyrosine kinases and their ephrin ligands participate in the control of neuronal growth and migration in a variety of contexts, but the mechanisms by which they guide neuronal motility are still incompletely understood. By using the enteric nervous system (ENS) of the tobacco hornworm Manduca sexta as a model system, we have explored whether Manduca ephrin (MsEphrin; a GPI-linked ligand) and its Eph receptor (MsEph) might regulate the migration and outgrowth of enteric neurons. During formation of the Manduca ENS, an identified set of approximately 300 neurons (EP cells) populates the enteric plexus of the midgut by migrating along a specific set of muscle bands forming on the gut, but the neurons strictly avoid adjacent interband regions. By determining the mRNA and protein expression patterns for MsEphrin and the MsEph receptor and by examining their endogenous binding patterns within the ENS, we have demonstrated that the ligand and its receptor are distributed in a complementary manner: MsEphrin is expressed exclusively by the migratory EP cells, whereas the MsEph receptor is expressed by midline interband cells that are normally inhibitory to migration. Notably, MsEphrin could be detected on the filopodial processes of the EP cells that extended up to but not across the midline cells expressing the MsEph receptor. These results suggest a model whereby MsEphrin-dependent signaling regulates the response of migrating neurons to a midline inhibitory boundary, defined by the expression of MsEph receptors in the developing ENS. PMID- 17348008 TI - Reactive plasticity in the dentate gyrus following bilateral entorhinal cortex lesions in cynomolgus monkeys. AB - Hippocampal structural plasticity induced by entorhinal cortex (EC) lesions has been studied extensively in the rat, but little comparable research has been conducted in primates. In the current study we assessed the long-term effects of bilateral aspiration lesions of the EC on multiple markers of circuit organization in the hippocampal dentate gyrus of young adult monkeys (Macaca fascicularis). Alternate histological sections were processed for the visualization of somatostatin and vesicular acetylcholine transporter (VAChT) immunoreactivity and acetylcholinesterase histochemistry (AChE). The markers revealed the distinct laminar organization of dentate gyrus circuitry for stereology-based morphometric quantification. Consistent with findings in rats, the volume of the somatostatin-immunopositive outer molecular layer (OML), innervated by projections from the EC, was decreased by 42% relative to control values. The inner molecular layer (IML) displayed a corresponding volumetric expansion in response to denervation of the OML as measured by AChE staining, but not when visualized for quantification by VAChT immunoreactivity. Nonetheless, stereological estimation revealed a 36% increase in the total length of VAChT positive cholinergic fibers in the IML after EC damage, along with no change in the OML. Together, these findings suggest that despite substantial species differences in the organization of hippocampal circuitry, the capacity for reactive plasticity following EC damage, previously documented in rats, is at least partly conserved in the primate dentate gyrus. PMID- 17348009 TI - Immunohistochemical localization of cocaine- and amphetamine-regulated transcript peptide in the brain of the catfish, Clarias batrachus (Linn.). AB - The organization of cocaine- and amphetamine-regulated transcript peptide (CARTp, 54-102) immunoreactivity was investigated in the brain of the catfish, Clarias batrachus. CARTp-immunoreactivity was observed in several granule cells of the olfactory bulbs, in dot-like terminals around mitral cells, and in the fibers of the medial olfactory tracts. While several groups of discrete cells in the telencephalon showed CARTp-immunoreactivity, the immunostained fibers were widely distributed in the area dorsalis and ventralis telencephali. Immunoreactivity was seen in several periventricular and a few magnocellular neurons, and in a dense fiber network throughout the preoptic area. Varying degrees of immunoreactive fibers were seen in the periventricular region in the thalamus, hypothalamus, and pituitary. Some neurons in the nucleus preglomerulosus medialis and lateralis, central nucleus of the inferior lobes, nucleus lobobulbaris of the posterior tuberculum, and nucleus recessus posterioris showed distinct CARTp immunoreactivity. Considerable immunoreactivity was seen in the optic tectum, rostral torus semicircularis, central pretectal area, and granule cells of the cerebellum. While only isolated immunoreactive cells were seen at three distinct sites in the metencephalon, a fiber network was seen in the facial and vagal lobes and periventricular and ventral regions of the medulla oblongata. The pattern of the CARTp distribution in the brain of C. batrachus suggests that it may play an important role in the processing of sensory information, the regulation of hormone secretion by hypophysial cell types, and motor and vegetative function. Finally, as in other animal species, CARTp seems to play a role in the processing of gustatory information. PMID- 17348010 TI - A recombinant allosteric lectin antagonist of HIV-1 envelope gp120 interactions. AB - The first, critical stage of HIV-1 infection is fusion of viral and host cellular membranes initiated by a viral envelope glycoprotein gp120. We evaluated the potential to form a chimeric protein entry inhibitor that combines the action of two gp120-targeting molecules, an allosteric peptide inhibitor 12p1 and a higher affinity carbohydrate-binding protein cyanovirin (CVN). In initial mixing experiments, we demonstrated that the inhibitors do not interfere with each other and instead show functional synergy in inhibiting viral cell infection. Based on this, we created a chimera, termed L5, with 12p1 fused to the C-terminal domain of CVN through a linker of five penta-peptide repeats. L5 revealed the same broad specificity as CVN for gp120 from a variety of clades and tropisms. By comparison to CVN, the L5 chimera exhibited substantially increased inhibition of gp120 binding to receptor CD4, coreceptor surrogate mAb 17b and gp120 antibody F105. These binding inhibition effects by the chimera reflected both the high affinity of the CVN domain and the allosteric action of the 12p1 domain. The results open up the possibility to form high potency chimeras, as well as noncovalent mixtures, as leads for HIV-1 envelope antagonism that can overcome potency limits and potential virus mutational resistance for either 12p1 or CVN alone. PMID- 17348011 TI - Time course and distribution of inflammatory and neurodegenerative events suggest structural bases for the pathogenesis of experimental autoimmune encephalomyelitis. AB - Murine models of experimental autoimmune encephalomyelitis (EAE) are important vehicles for studying the effects of genetic manipulation on disease processes related to multiple sclerosis (MS). Currently, a comprehensive assessment of EAE pathogenesis with respect to inflammatory and degenerating neuronal elements is lacking. By using Fluoro-jade histochemistry to mark neurodegeneration and dual immunostaining to follow T-cell, microglial, and vascular responses, the time course and distribution of pathological events in EAE was surveyed. C57BL/6J mice were killed at 7, 10, 14, 21 or 35 days after vaccination with the myelin oligodendrocyte glycoprotein peptide MOG(35-55). Disease onset occurred at day 14 and peaked at day 21. Early T-cell infiltration and microglial activation in periventricular and superficial white matter structures adjacent to meninges suggested initial recruitment of effector T cells via the cerebrospinal fluid and choroid plexus. This was associated with microglial activation at distal sites along the same white matter tracts, with subsequent vascular recruitment of T cells associated with further injury. Systematic examination of the entire CNS supported this two-step model of EAE pathogenesis, with inflammation and neurodegeneration commencing at similar times and affecting multiple levels of predominantly sensory central pathways, including their terminal fields. This included aspects of the visual, auditory/vestibular, somatosensory (lemniscal), and proprioceptive (spinocerebellar) systems. The early targeting of visual and periventricular structures followed by more widespread CNS involvement is consistent with common presenting signs in human MS patients and suggestive of a similar basis in neuropathology. PMID- 17348012 TI - Conformational states and folding pathways of peptides revealed by principal independent component analyses. AB - Principal component analysis is a powerful method for projecting multidimensional conformational space of peptides or proteins onto lower dimensional subspaces in which the main conformations are present, making it easier to reveal the structures of molecules from e.g. molecular dynamics simulation trajectories. However, the identification of all conformational states is still difficult if the subspaces consist of more than two dimensions. This is mainly due to the fact that the principal components are not independent with each other, and states in the subspaces cannot be visualized. In this work, we propose a simple and fast scheme that allows one to obtain all conformational states in the subspaces. The basic idea is that instead of directly identifying the states in the subspace spanned by principal components, we first transform this subspace into another subspace formed by components that are independent of one other. These independent components are obtained from the principal components by employing the independent component analysis method. Because of independence between components, all states in this new subspace are defined as all possible combinations of the states obtained from each single independent component. This makes the conformational analysis much simpler. We test the performance of the method by analyzing the conformations of the glycine tripeptide and the alanine hexapeptide. The analyses show that our method is simple and quickly reveal all conformational states in the subspaces. The folding pathways between the identified states of the alanine hexapeptide are analyzed and discussed in some detail. PMID- 17348013 TI - Update on the molecular biology of malignant mesothelioma. AB - Malignant mesothelioma (MM) is a highly aggressive tumor with a very poor prognosis. The disease is largely unresponsive to conventional chemotherapy or radiotherapy, and most patients die within 10-17 months of the first symptoms. Novel, more effective therapeutic strategies are needed for this inexorably fatal disease. Improvement in our understanding of the molecular biology of MM has identified promising new candidates for targeted treatments. In this review the key molecular signaling pathways, including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), Wnt, and the cell cycle control genes p53, pRb, and bcl-2 that appear to play an important role in the pathogenesis of MM are explored. PMID- 17348014 TI - Cytological organization of the central gelatinosa in the turtle spinal cord. AB - This paper deals with the cytological organization of the central gelatinosa (CG) in the spinal cord of juvenile (2-12 months) turtles. We found two main cell classes in the CG: one with characteristics of immature neurons, the other identified as radial glia (RG). The cells surrounding the central canal formed radial conglomerates in such a way that the RG lamellae covered the immature neurons. We found three major subpopulations of RG that expressed S-100, glial fibrillary acidic protein, or both proteins. Electron microscopic images showed gap junctions interconnecting RG. As with the mammalian neuroepithelial cells, most CG cells displayed intrinsic polarity expressed by structural and molecular differences between the most apical and basal cell compartments. The apical zone was characterized by the occurrence of a single cilium associated with a conspicuous centrosomal complex. We found a prominent expression of the PCM-1 centrosomal protein concentrated close to the central canal lumen. In the particular case of RG, the peripheral end feet contacted the subpial basement membrane. We also found "transitional cell forms" difficult to classify by the usual imaging approaches. Functional clues obtained by patch-clamp recordings of CG cells defined some of them as already committed to follow the neuronal lineage, whereas others had properties of less mature or migrating cells. The CG appeared as a richly innervated region receiving terminal branches from nerve plexuses expressing gamma-aminobutyric acid, serotonin, and glutamate. The results presented here support our previous studies indicating that the CG is an extended neurogenic niche along the spinal cord of turtles. PMID- 17348015 TI - Differential modes of termination of amygdalothalamic and amygdalocortical projections in the monkey. AB - The amygdala complex participates in multiple systems having to do with affective processes. It has been implicated in human disorders of social and emotional behavior, such as autism. Of the interconnected functional networks, considerable research in rodents and primates has focused on connections between the amygdala and orbitofrontal cortex (OFC). The amygdala projects to OFC by both a direct amygdalocortical (AC) pathway and an indirect pathway through mediodorsal thalamus. In the rat, retrograde tracer experiments indicate that the AC and amygdalothalamic (AT) pathways originate from separate populations, and may therefore convey distinctive information, although the characteristics of these pathways remain unclear. To investigate this issue in monkeys we made anterograde tracer injections in the basolateral amygdala complex (BLC; n = 3). Three distinctive features were found preferentially associated with the AT or AC pathways. First, AT terminations are large (average diameter = 3.5 microm; range = 1.2-7.0 microm) and cluster around proximal dendrites, in contrast with small bouton AC terminations. Second, AT terminations form small arbors (diameter approximately 0.1 mm), while AC are widely divergent (often >1.0 mm long). The AT terminations features are reminiscent of large bouton, "driver" corticothalamic terminations. Finally, AC but not AT terminations are positive for zinc (Zn), a neuromodulator associated with synaptic plasticity. From these results we suggest that AC and AT terminations originate from distinct populations in monkey as well as in rodent. Further work is necessary to determine the degree and manner of their segregation and how these subsystems interact within a broader connectivity network. PMID- 17348016 TI - Modification of classical neurochemical markers in identified primary afferent neurons with Abeta-, Adelta-, and C-fibers after chronic constriction injury in mice. AB - It is functionally important to differentiate between primary afferent neurons with A-fibers, which are nociceptive or nonnociceptive, and C-fibers, which are mainly nociceptive. Neurochemical markers such as neurofilament 200 (NF200), substance P (SP), and isolectin B4 (IB4) have been useful to distinguish between A- and C-fiber neurons. However, the expression patterns of these markers change after peripheral nerve injury, so that it is not clear whether they still distinguish between fiber types in models of neuropathic pain. We identified neurons with Abeta-, Adelta-, and C-fibers by their conduction velocity (corrected for utilization time) in dorsal root ganglia taken from mice after a chronic constriction injury (CCI) of the sciatic nerve and control mice, and later stained them for IB4, SP, calcitonin gene-related peptide (CGRP), NF200, and neuropeptide Y (NPY). NF200 remained a good marker for A-fiber neurons, and IB4 and SP remained good markers for C-fiber neurons after CCI. NPY was absent in controls but was expressed in A-fiber neurons after CCI. After CCI, a group of C fiber neurons emerged that expressed none of the tested markers. The size distribution of the markers was investigated in larger samples of unidentified dorsal root ganglion neurons and, together with the results from the identified neurons, provided only limited evidence for the expression of SP in Abeta-fiber neurons after CCI. The extent of up-regulation of NPY showed a strong inverse correlation with the degree of heat hyperalgesia. PMID- 17348017 TI - Morphological and functional differentiation of HSG cells: role of extracellular matrix and trpc 1. AB - A human salivary intercalated duct cell line (HSG) is capable of morphological change to acinar-type cells, and of salivary amylase (AMY1) expression, by culturing on basement membrane extracts (BME). The aim of this study was to determine the critical conditions for functional and morphological differentiation of HSG cells and to establish if the processes are related. Cells were grown on BMEs that had different protein concentrations and growth factor content, and then examined with respect to morphology and AMY1 expression. To investigate the role of intracellular calcium in amylase expression, a pcDNA3.1 TRPC1alpha construct was used to overexpress htrp1alpha, which mediates the store operated calcium entry in HSG cells. Expression of the AMY1, TRPC1alpha and beta genes was quantified by means of real time RT-PCR. Growth factor-reduced BME (12.8 mg/ml) induced multicellular acinar structures with lumen formation but without stimulation of either AMY1 or TRPC1. HSG cells cultured on higher concentration BME (17.5 or 16.4 mg/ml) formed reticular networks. AMY1 expression increased both on growth factor-reduced BME (17.5 mg/ml: 3.0-fold, P < 0.001) and on regular BME (16.4 mg/ml: 3.7-fold, P < 0.001) accompanied by a slight increase in expression of TRPC1alpha and TRPC1beta. Overexpression of htrp1alpha did not cause any significant changes in AMY expression, though it attenuated the BME (17.5 mg/ml)-induced AMY1 upregulation. Overall, the higher protein concentration BME favors amylase expression in HSG cells, whereas the lower concentration causes marked morphological changes. PMID- 17348018 TI - Developmental origin and identity of song system neurons born during vocal learning in songbirds. AB - New neurons are added to the forebrain song control regions high vocal center (HVC) and Area X of juvenile songbirds but the identity and site of origin of these cells have not been fully characterized. We used oncoretroviral vectors to genetically label neuronal progenitors in different regions of the zebra finch lateral ventricle. A region corresponding to the mammalian medial and lateral ganglionic eminences generated medium spiny neurons found in Area X and in the striatum surrounding Area X, and at least two classes of interneurons found in HVC. In addition, our experiments indicate that the HVC projection neurons that project into nucleus robust nucleus of the arcopallium (RA) are born locally from the ventricular region immediately dorsal to HVC. The ability to genetically target neuron subpopulations that give rise to different song system cell types provides a tool for specific genetic manipulations of these cell types. In addition, our results suggest striking similarities between neurogenesis in the embryonic mammalian brain and in the brain of the juvenile songbird and provide further evidence for the existence of conserved cell types in the forebrain for birds and mammals. PMID- 17348019 TI - Crystal structure of a novel single-stranded DNA binding protein from Mycoplasma pneumoniae. PMID- 17348020 TI - Acute L-glutamine deprivation compromises VEGF-a upregulation in A549/8 human carcinoma cells. AB - Tumor ischemia participates in angiogenesis and cancer progression through cellular responses to hypoxia and nutrient deprivation. However, the contribution of amino acids limitation to this process remains poorly understood. Using serum free cell culture conditions, we tested the impact of L-glutamine deprivation on metabolic and angiogenic responses in A549/8 carcinoma cells. In these cells, lowering glutamine concentration modified the cell cycle distribution and significantly induced apoptosis/necrosis. Although glutamine deprivation led to a HIF-independent increase in VEGF-A mRNA, the corresponding protein level remained low and correlated with the inhibition of protein synthesis and activation of the GCN2/eIF2alpha pathway. Limitation of glutamine availability also hampers hypoxia and hypoglycemia-induced VEGF-A protein upregulation. Thus, glutamine deprivation may have no direct effect on VEGF-dependent angiogenesis, compared to hypoxia or to glucose deprivation, and may instead be detrimental to cancer progression by antagonizing ischemia-induced stresses. PMID- 17348021 TI - EGF-R regulates MMP function in fibroblasts through MAPK and AP-1 pathways. AB - EGF-R regulates cell proliferation, migration, and invasion in fibroblasts. However, the connection of EGF-R with downstream signaling pathways mediating these responses has remained elusive. Here we provide genetic and biochemical evidence that EGF-R- and AP-1-mediated signals are required for MMP expression and collagen contraction in fibroblasts. In EGF-R (-/-) mouse embryonal fibroblasts, basal and inducible expression of several MMPs, including MMP-2, -3, and -14 is impaired in comparison to wild-type counterparts. The loss of MMP expression is associated with a suppression of EGF-induced Erk and Jnk activities, and AP-1 DNA-binding and transactivation capacities. While inhibition of Jnk mainly prevents EGF-induced phosphorylation of c-Jun, inhibition of Erk pathway suppresses both the expression and phosphorylation of c-Jun and c-Fos proteins. Moreover, the expression of MMP-3 and -14, and collagen contraction is partially prevented by Mek/Erk and Jnk inhibitors. However, Jnk inhibitor also suppresses cell growth independently of EGF-R activity. The central role of AP-1 as a mediator of EGF-R signaling in fibroblasts is emphasized by the finding that expression of a dominant negative c-Jun downregulates the expression of MMP-3. Conversely, expression of a constitutively active Mek1 can induce MMP-3 expression independently of upstream signals. The results indicate that ERK pathway and AP-1 are downstream effectors of the EGF-R-mediated MMP-3 expression and collagen contraction in fibroblasts. PMID- 17348022 TI - Detection of structural changes in a cofactor binding protein by using a wheat germ cell-free protein synthesis system coupled with unnatural amino acid probing. AB - A cell-free protein synthesis system is a powerful tool with which unnatural amino acids can be introduced into polypeptide chains. Here, the authors describe unnatural amino acid probing in a wheat germ cell-free translation system as a method for detecting the structural changes that occur in a cofactor binding protein on a conversion of the protein from an apo-form to a holo-form. The authors selected the FMN-binding protein from Desulfovibrio vulgaris as a model protein. The apo-form of the protein was synthesized efficiently in the absence of FMN. The purified apo-form could be correctly converted to the holo-form. Thus, the system could synthesize the active apo-form. Gel filtration chromatography, analytical ultracentrifugation, and circular dichroism-spectra studies suggested that the FMN-binding site of the apo-form is open as compared with the holo-form. To confirm this idea, the unnatural amino acid probing was performed by incorporating 3-azido-L-tyrosine at the Tyr35 residue in the FMN binding site. The authors optimized three steps in their system. The introduced 3 azido-L-tyrosine residue was subjected to specific chemical modification by a fluorescein-triarylphosphine derivative. The initial velocity of the apo-form reaction was 20 fold faster than that of the holo-form, demonstrating that the Tyr35 residue in the apo-form is open to solvent. PMID- 17348023 TI - Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging. AB - Neurofibromatosis 1 (NF1) is a common genetic disease that predisposes patients to peripheral nerve tumors and central nervous system (CNS) abnormalities including low-grade astrocytomas and cognitive disabilities. Using mice with glial fibrillary acidic protein (GFAP)-targeted Nf1 loss (Nf1(GFAP)CKO mice), we found that Nf1(-/-) astrocytes proliferate faster and are more invasive than wild type astrocytes. In light of our previous finding that aberrant expression of the MET receptor tyrosine kinase contributes to the invasiveness of human NF1 associated malignant peripheral nerve sheath tumors, we sought to determine whether MET expression is aberrant in the brains of Nf1 mutant mice. We found that Nf1(-/-) astrocytes express slightly more MET than wild-type cells in vitro, but do not express elevated MET in situ. However, fiber tracts containing myelinated axons in the hippocampus, midbrain, cerebral cortex, and cerebellum express higher than normal levels of MET in older (> or =6 months) Nf1(GFAP)CKO mice. Both Nf1(GFAP)CKO and wild-type astrocytes induced MET expression in neurites of wild-type hippocampal neurons in vitro, suggesting that astrocyte derived signals may induce MET in Nf1 mutant mice. Because the Nf1 gene product functions as a RAS GTPase, we examined MET expression in the brains of mice with GFAP-targeted constitutively active forms of RAS. MET was elevated in axonal fiber tracts in mice with active K-RAS but not H-RAS. Collectively, these data suggest that loss of Nf1 in either astrocytes or GFAP(+) neural progenitor cells results in increased axonal MET expression, which may contribute to the CNS abnormalities in children and adults with NF1. PMID- 17348025 TI - Culture conditions affect proliferative responsiveness of olfactory ensheathing glia to neuregulins. AB - Olfactory ensheathing glia (OEG) have been used to improve outcome after experimental spinal cord injury and are being trialed clinically. Their rapid proliferation in vitro is essential to optimize clinical application, with neuregulins (NRG) being potential mitogens. We examined the effects of NRG-1beta, NRG-2alpha, and NRG3 on proliferation of p75-immunopurified adult OEG. OEG were grown in serum-containing medium with added bovine pituitary extract and forskolin (added mitogens) or in serum-containing medium (no added mitogens). Cultures were switched to chemically defined medium (no added mitogens or serum), NRG added and OEG proliferation assayed using BrdU. OEG grown initially with added mitogens were not responsive to added NRGs and pre-exposure to forskolin and pituitary extract increased basal proliferation rates so that OEG no longer responded to added NRG. However, NRG promoted proliferation but only if cells were initially grown in mitogen-free medium. Primary OEG express ErbB2, ErbB3, and small levels of ErbB4 receptors; functional blocking indicates that ErbB2 and ErbB3 are the main NRG receptors utilized in the presence of NRG-1beta. The long term stimulation of OEG proliferation by initial culture conditions raises the possibility of manipulating OEG before therapeutic transplantation. PMID- 17348024 TI - Double-stranded RNA induces iNOS gene expression in Schwann cells, sensory neuronal death, and peripheral nerve demyelination. AB - Inflammation in the peripheral nervous system (PNS) is one of the characteristics of virus-induced peripheral neuropathy. In this inflammatory response, Schwann cells are actively involved. Previously, toll-like receptor 3 (TLR3) was reported as a receptor for double-stranded RNA (dsRNA) that induces antiviral and inflammatory responses in cells of the innate immune system. In this study, we investigated the expression and putative role of TLR3 in Schwann cells. TLR3 was constitutively expressed in Schwann cells. Stimulation with polyinosinic polycytidylic acid, a synthetic dsRNA analogue, induced the expression of inducible nitric oxide synthase (iNOS) gene in Schwann cells. Studies on the intracellular signal transduction pathways using iSC, an immortalized Schwann cell line, revealed that dsRNA induces the activation of NF-kappaB, p38, and c Jun N-terminal kinase (JNK). The activation of NF-kappaB, p38, JNK, and dsRNA dependent protein kinase is required for dsRNA-mediated iNOS gene expression. However, the activation of PI3 kinase and GSK-3beta inhibited iNOS gene induction, a process mediated by their inhibitory effects on NF-kappaB and p38 activation. dsRNA-induced NO production caused neuronal cell death in cultured dorsal root ganglion. Finally, the introduction of dsRNA into the rat sciatic nerve induced iNOS gene expression and peripheral nerve demyelination in vivo. Taken together, these data suggest that viral RNA may induce inflammatory Schwann cell activation via TLR3 and peripheral nerve damage in the PNS. PMID- 17348026 TI - Free energy landscape of a biomolecule in dihedral principal component space: sampling convergence and correspondence between structures and minima. AB - Dihedral principal component analysis (dPCA) has recently been developed and shown to display complex features of the free energy landscape of a biomolecule that may be absent in the free energy landscape plotted in principal component space due to mixing of internal and overall rotational motion that can occur in principal component analysis (PCA) [Mu et al., Proteins: Struct Funct Bioinfo 2005;58:45-52]. Another difficulty in the implementation of PCA is sampling convergence, which we address here for both dPCA and PCA using a tetrapeptide as an example. We find that for both methods the sampling convergence can be reached over a similar time. Minima in the free energy landscape in the space of the two largest dihedral principal components often correspond to unique structures, though we also find some distinct minima to correspond to the same structure. PMID- 17348027 TI - The green tea compound, (-)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cells. AB - Green tea has been reported as potential dietary protection against numerous cancers and has been shown to have activity in bladder tumor inhibition in different animal models. The goal of this study was to examine the effects of (-) epigallocatechin gallate (EGCG-the major phytochemical in green tea) on growth inhibition and behavior of human bladder carcinoma cells and to identify the altered signaling pathway(s) underlying the response to EGCG exposure. EGCG inhibited the in vitro growth of invasive bladder carcinoma cells with an IC(50) range of 70-87 microM. At a concentration of 20 microM, EGCG decreased the migratory potential of bladder carcinoma cells with concomitant activation of p42/44 MAPK and STAT3 and inactivation of Akt. Using biochemical inhibitors of MAPK/ERK, and siRNA to knockdown STAT3 and Akt, inhibition of migration was recorded associated with Akt but not MAPK/ERK or STAT3 signaling in bladder cells. In addition, EGCG downregulated N-cadherin in a dose-dependent manner where reduction in N-cadherin expression paralleled declining migratory potential. Continuous feeding of EGCG to mice prior to and during the establishment of bladder carcinoma xenografts in vivo revealed >50% reduction in mean final tumor volume (P pi* transition. Furthermore, all three classes of compounds show readily observable phosphorescence in solution, which was determined by time gated detection at low temperature. PMID- 17348056 TI - Theoretical study of the reaction of vitamin B6 with 1O2. AB - Singlet oxygen is known to cause oxidative stress in cells, leading to severe damage (e.g., lipid peroxidation, membrane degradation, mutagenic alterations to DNA, protein misfunctionality). Recently, pyridoxine has been discovered to be capable of quenching singlet oxygen, however, the mechanism of this reaction remains essentially unknown. In this work, we have investigated four sets of reactions: 1) 1,3-addition to a double bond connected to a hydrogen-carrying group, resulting in the formation of allylic hydroperoxides; 2) [pi2+pi2] 1,2 cycloaddition to an isolated double bond, resulting in the formation of 1,2 peroxides; 3) 1,4-cycloaddition to a system containing at least two conjugated double bonds, resulting in the formation of the so-called 1,4-peroxides; 4) 1,4 addition to phenols and naphthols with the formation of hydroperoxide ketones. Thermodynamically, reaction 4 and the 6(9), 3(8), and 5(8) cases of reaction 1 are the most exergonic ones, with energies ranging from -16 to -18 kcal mol(-1). Furthermore, reaction 4 shows the lowest barrier through the reaction path, and is predicted to be the preferred mechanism for the pyridoxine + singlet-oxygen reaction, which is in agreement with previous experimental results. PMID- 17348057 TI - N-heterocyclic carbenes as organocatalysts. AB - Organocatalyzed reactions represent an attractive alternative to metal-catalyzed processes notably because of their lower cost and benign environmental impact in comparison to organometallic catalysis. In this context, N-heterocyclic carbenes (NHCs) have been studied for their ability to promote primarily the benzoin condensation. Lately, dramatic progress in understanding their intrinsic properties and in their synthesis have made them available to organic chemists. This has resulted in a tremendous increase of their scope and in a true explosion of the number of papers reporting NHC-catalyzed reactions. Here, we highlight the ever-increasing number of reactions that can be promoted by N-heterocyclic carbenes. PMID- 17348058 TI - Viruses as building blocks for materials and devices. AB - From the viewpoint of a materials scientist, viruses can be regarded as organic nanoparticles. They are composed of a small number of different (bio)polymers: proteins and nucleic acids. Many viruses are enveloped in a lipid membrane and all viruses do not have a metabolism of their own, but rather use the metabolic machinery of a living cell for their replication. Their surface carries specific tools designed to cross the barriers of their host cells. The size and shape of viruses, and the number and nature of the functional groups on their surface, is precisely defined. As such, viruses are commonly used in materials science as scaffolds for covalently linked surface modifications. A particular quality of viruses is that they can be tailored by directed evolution by taking advantage of their inbuilt colocalization of geno- and phenotypes. The powerful techniques developed by life sciences are becoming the basis of engineering approaches towards nanomaterials, opening a wide range of applications far beyond biology and medicine. PMID- 17348059 TI - First-principles considerations in the design of Pd-alloy catalysts for oxygen reduction. PMID- 17348060 TI - Monocapped trigonal-prismatic transition-metal heptaazides: syntheses, properties, and structures of [Nb(N3)7]2- and [Ta(N3)7]2-. PMID- 17348061 TI - Rapid multiphase carbonylation reactions by using a microtube reactor: applications in positron emission tomography 11C-radiolabeling. PMID- 17348062 TI - A metallocavitand functioning as a container for anions: formation of noncovalent linear assemblies mediated by a cyclodextrin-entrapped NO3- ion. PMID- 17348063 TI - Beryllium displacement of H+ from strong hydrogen bonds. PMID- 17348064 TI - Au34-: a chiral gold cluster? PMID- 17348065 TI - Propargylic esters in gold catalysis: access to diversity. PMID- 17348066 TI - Chemical cotton stalk destruction for maintenance of host-free periods for the control of overwintering boll weevil in tropical and subtropical climates. AB - In the Lower Rio Grande Valley (LRGV) of Texas, cotton regrows and produces fruit from undestroyed stalks throughout the winter, and in spring weevils from such locations become a serious threat. The success of the boll weevil eradication program, which was reintroduced in the LRGV in 2005, will be dependent on thorough stalk destruction following harvest. However, adverse weather conditions and conservation tillage often impede immediate and complete stalk destruction using typical tool implements, and alternative stalk control methods are needed. This study provides an examination of the efficacy for cotton stalk destruction of different herbicides (thifensulfuron-methyl + tribenuron-methyl, dicamba diolamine, 2,4-D-dimethylammonium, flumioxazin, 2,4-DB-dimethylammonium and carfentrazone-ethyl) and their rates, spray volumes and application timings on shredded or standing cotton stalks after stripper or picker harvest. None of the tested herbicides, except 2,4-D-dimethylammonium, stopped post-harvest cotton regrowth and fruiting. 2,4-D-dimethylammonium sprayed once (0 or 7 days) after cotton was harvested at 1 lb AE acre(-1) (1.12 kg ha(-1)), in a spray volume of 10 gal water acre(-1) (93.5 L ha(-1)) with 5 mL L(-1) surfactant, was highly effective in stalk destruction (72-90%). The best results were achieved when the herbicide was applied immediately after the cotton was shredded, followed by standing stripper-harvested and standing picker-harvested cotton. 2,4-D dimethylammonium applied twice, 0 and 14 (or 21) days after cotton harvest, was 100% effective in killing stalks, regardless of whether they were shredded or standing, or whether harvest was by stripper or picker. These findings showed that 2,4-D-dimethylammonium cotton stalk destruction eliminated food and reproductive opportunities for managing overwintering boll weevils [Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae)]. PMID- 17348068 TI - Allelopathy--a natural alternative for weed control. AB - Allelopathy studies the interactions among plants, fungi, algae and bacteria with the organisms living in a certain ecosystem, interactions that are mediated by the secondary metabolites produced and exuded into the environment. Consequently, allelopathy is a multidisciplinary science where ecologists, chemists, soil scientists, agronomists, biologists, plant physiologists and molecular biologists offer their skills to give an overall view of the complex interactions occurring in a certain ecosystem. As a result of these studies, applications in weed and pest management are expected in such different fields as development of new agrochemicals, cultural methods, developing of allelopathic crops with increased weed resistance, etc. The present paper will focus on the chemical aspects of allelopathy, pointing out the most recent advances in the chemicals disclosed, their mode of action and their fate in the ecosystem. Also, attention will be paid to achievements in genomics and proteomics, two emerging fields in allelopathy. Rather than being exhaustive, this paper is intended to reflect a critical vision of the current state of allelopathy and to point to future lines of research where in the authors' opinion the main advances and applications could and should be expected. PMID- 17348069 TI - Weeding with allelochemicals and allelopathy--a commentary. PMID- 17348070 TI - Entomopathogenicity of native bacteria from Anastrepha fraterculus and Ceratitis capitata against the pest Phyllocnistis citrella. AB - In Piura (Peru), the pest Phyllocnistis citrella Stainton damages the photosynthetic rate and new bud production of Citrus aurantiifolia Swingle (sweet lemon), decreasing the yield, productivity and commercial price of its fruit. Biological control was evaluated through the crossed effect of bacteria obtained from pests (Anastrepha fraterculus Wied., Ceratitis capitata Wied. and Rhynchophorus palmarum L.) that are pathogenic against their original host species. Enterobacter cloacae (Jordan) Hormaeche & Edwards and Serratia marcescens Bizio (from A. fraterculus and C. capitata) and Pseudomonas mendocina Palleroni (from R. palmarum) were used against P. citrella. The bacterial strains were inoculated into its food and the accumulated mortality was evaluated. Larvae of P. citrella treated with P. mendocina had the highest mortality (66.7%). These bacterial species were entomopathogenic against the original source pest in laboratory and greenhouse bioassays, and this result widens the pathological activity range of these bacterial species. PMID- 17348071 TI - Effects of glyphosate on soil microbial communities and its mineralization in a Mississippi soil. AB - Transgenic glyphosate-resistant (GR) soybean [Glycine max (L.) Merr.] has enabled highly effective and economical weed control. The concomitant increased application of glyphosate could lead to shifts in the soil microbial community. The objective of these experiments was to evaluate the effects of glyphosate on soil microbial community structure, function and activity. Field assessments on soil microbial communities were conducted on a silt loam soil near Stoneville, MS, USA. Surface soil was collected at time of planting, before initial glyphosate application and 14 days after two post-emergence glyphosate applications. Microbial community fatty acid methyl esters (FAMEs) were analyzed from these soil samples and soybean rhizospheres. Principal component analysis of the total FAME profile revealed no differentiation between field treatments, although the relative abundance of several individual fatty acids differed significantly. There was no significant herbicide effect in bulk soil or rhizosphere soils. Collectively, these findings indicate that glyphosate caused no meaningful whole microbial community shifts in this time period, even when applied at greater than label rates. Laboratory experiments, including up to threefold label rates of glyphosate, resulted in up to a 19% reduction in soil hydrolytic activity and small, brief (<7 days) changes in the soil microbial community. After incubation for 42 days, 32-37% of the applied glyphosate was mineralized when applied at threefold field rates, with about 9% forming bound residues. These results indicate that glyphosate has only small and transient effects on the soil microbial community, even when applied at greater than field rates. PMID- 17348072 TI - Gold- and indium-catalyzed synthesis of 3- and 6-sulfonylindoles from ortho alkynyl-N-sulfonylanilines. PMID- 17348074 TI - Control of magnetic properties through external stimuli. AB - The magnetic properties of many magnetic materials can be controlled by external stimuli. The principal focus here is on the thermal, photochemical, electrochemical, and chemical control of phase transitions that involve changes in magnetization. The molecular compounds described herein range from metal complexes, through pure organic compounds to composite materials. Most of the Review is devoted to the properties of valence-tautomeric compounds, molecular magnets, and spin-crossover complexes, which could find future application in memory devices or optical switches. PMID- 17348075 TI - A classical silver carbonyl complex [{MeB[3-(Mes)pz]3}Ag(CO)] and the related silver ethylene adduct [{MeB[3-(Mes)pz]3}Ag(C2H4)]. PMID- 17348076 TI - An intermolecular double [2+2] cyclodimerization of a tetraalkyne. PMID- 17348080 TI - Analyzing survival curves at a fixed point in time. AB - A common problem encountered in many medical applications is the comparison of survival curves. Often, rather than comparison of the entire survival curves, interest is focused on the comparison at a fixed point in time. In most cases, the naive test based on a difference in the estimates of survival is used for this comparison. In this note, we examine the performance of alternatives to the naive test. These include tests based on a number of transformations of the survival function and a test based on a generalized linear model for pseudo observations. The type I errors and power of these tests for a variety of sample sizes are compared by a Monte Carlo study. We also discuss how these tests may be extended to situations where the data are stratified. The pseudo-value approach is also applicable in more detailed regression analysis of the survival probability at a fixed point in time. The methods are illustrated on a study comparing survival for autologous and allogeneic bone marrow transplants. PMID- 17348081 TI - On robustness of marginal regression coefficient estimates and hazard functions in multivariate survival analysis of family data when the frailty distribution is mis-specified. AB - The shared frailty model is an extension of the Cox model to correlated failure times and, essentially, a random effects model for failure time outcomes. In this model, the latent frailty shared by individual members in a cluster acts multiplicatively as a factor on the hazard function and is typically modelled parametrically. One commonly used distribution is gamma, where both shape and scale parameters are set to be the same to allow for unique identification of baseline hazard function. It is popular because it is a conjugate prior, and the posterior distribution possesses the same form as gamma. In addition, the parameter can be interpreted as a time-independent cross-ratio function, a natural extension of odds ratio to failure time outcomes. In this paper, we study the effect of frailty distribution mis-specification on the marginal regression estimates and hazard functions under assumed gamma distribution with an application to family studies. The simulation results show that the biases are generally 10% and lower, even when the true frailty distribution deviates substantially from the assumed gamma distribution. This suggests that the gamma frailty model can be a practical choice in real data analyses if the regression parameters and marginal hazard function are of primary interest and individual cluster members are exchangeable with respect to their dependencies. PMID- 17348082 TI - A covariate adjusted two-stage allocation design for binary responses in randomized clinical trials. AB - In the present work, we develop a two-stage allocation rule for binary response using the log-odds ratio within the Bayesian framework allowing the current allocation to depend on the covariate value of the current subject. We study, both numerically and theoretically, several exact and limiting properties of this design. The applicability of the proposed methodology is illustrated by using some data set. We compare this rule with some of the existing rules by computing various performance measures. PMID- 17348083 TI - Powerful short-cuts for multiple testing procedures with special reference to gatekeeping strategies. AB - In this paper we present a general testing principle for a class of multiple testing problems based on weighted hypotheses. Under moderate conditions, this principle leads to powerful consonant multiple testing procedures. Furthermore, short-cut versions can be derived, which simplify substantially the implementation and interpretation of the related test procedures. It is shown that many well-known multiple test procedures turn out to be special cases of this general principle. Important examples include gatekeeping procedures, which are often applied in clinical trials when primary and secondary objectives are investigated, and multiple test procedures based on hypotheses which are completely ordered by importance. We illustrate the methodology with two real clinical studies. PMID- 17348084 TI - Estimation of vaccine efficacy and the vaccination threshold. AB - This paper considers the effect of imperfect vaccination in a susceptible infected-removal (SIR) epidemic model. The minimum proportion of the population that needs to be vaccinated to prevent a major epidemic depends on the vaccine efficacy and the basic reproductive rate for the SIR model, allowing for imperfect and variable vaccination. Martingale theory is used to derive estimates and associated standard errors for these parameters. Asymptotic properties of the resulting estimators are investigated. Data for a mumps outbreak are used as an illustrative example. PMID- 17348085 TI - Electron capture atmospheric pressure photoionization mass spectrometry: analysis of fullerenes, perfluorinated compounds, and pentafluorobenzyl derivatives. AB - An electron capture (EC) ionization mechanism has been found to be highly efficient in negative-ion atmospheric pressure photoionization (APPI) for the analysis of compounds with positive electron affinity (EA). Using negative-ion APPI, we first report the sensitive detection of natural electrophores with limited polarity, such as fullerenes and perfluorinated compounds, by mass spectrometry (MS). Using direct infusion on a quadrupole time-of-flight (QTOF) mass spectrometer, the limits of detection (LODs) for C(60) and perfluoromethylcyclohexane were determined to be 0.15 pg (0.2 fmol) and 1 femtoliter (fL) ( approximately 1.5 pg or 4.3 fmol), respectively. As the EA of the analyte increases, the detection sensitivity is enhanced. Making use of the accurate mass measurement capability of the QTOF mass spectrometer, we were able to investigate the elemental composition of the ions in each spectrum and attribute the observed high sensitivity to an EC-initiated ionization process. The proposed EC ionization mechanism is further supported by the observation of a dissociative EC reaction of pentafluorobenzyl (PFB)-derivatized phenols. The analysis of phenols by EC-APPI of their PFB derivatives resulted in very high sensitivity, with the lowest reported LOD of approximately 0.17 pg (0.5 fmol) being for 2,4-dinitrophenol. For future LC/EC-APPI-MS applications, the effect of additives and solvents on sensitivity was also tested and reported. PMID- 17348087 TI - Study of bis(bibenzyls) in bryophytes using electron ionization time-of-flight and electrospray ionization triple-quadrupole mass spectrometry. AB - A detailed analysis of mass spectra generated from bis(bibenzyl) compounds in bryophytes under electron ionization time-of-flight (EI-TOF) and electrospray ionization triple-quadrupole (ESI-TQ) mass spectrometry conditions is reported. Proposed structures of the fragment ions were obtained by tracking the functional groups of 15 bis(bibenzyls), the structures of which are similar except for some alkoxyl substituents and linkage sites of biphenyl ether bonds. The elucidation was aided by the use of accurate mass measurements. Attempts have been made to provide rational pathways for the formation of these fragment ions, and a generalized fragmentation mechanism is proposed. The bis(bibenzyls) mentioned in this study include three types according to their structure characteristics, i.e. one biphenyl ether bond (A-type), two biphenyl ether bonds (B-type), one biphenyl ether and one biphenyl bond (C-type). The three types display different EI-MS and ESI-MS/MS product profiles, by which the bis(bibenzyl) type and the number of alkoxyl substituents can be identified. Isomers of bis(bibenzyls) can be differentiated to some extent, while the linkage sites of biphenyl ether bonds are difficult to identify. The structure-fragmentation relationships will facilitate the characterization of other bis(bibenzyls) and this will be of value for the high-throughput screening of novel bis(bibenzyls) in bryophytes. PMID- 17348086 TI - Evaluating high time-resolved changes in carbon isotope ratio of respired CO2 by a rapid in-tube incubation technique. AB - Recent insights into fractionation during dark respiration and rapid dynamics in isotope signatures of leaf- and ecosystem-respired CO(2) indicate the need for new methods for high time-resolved measurements of the isotopic signature of respired CO(2) (delta(13)C(res)). We present a rapid and simple method to analyse delta(13)C(res) using an in-tube incubation technique and an autosampler for small septum-capped vials. The effect of storage on the delta(18)O and delta(13)C ratios of ambient CO(2) concentrations was tested with different humidity and temperatures. delta(13)C ratios remained stable over 72 h, whereas delta(18)O ratios decreased after 24 h. Storage at 4 degrees C improved the storage time for delta(18)O. Leaves or leaf discs were incubated in the vials, flushed with CO(2) free air and respired CO(2) was automatically sampled within 5 min on a microGas autosampler interfaced to a GV-Isoprime isotope ratio mass spectrometer. Results were validated by simultaneous on-line gas-exchange measurements of delta(13)C(res) of attached leaves. This method was used to evaluate the short term (5-60 min) and diurnal dynamics of delta(13)C(res) in an evergreen oak (Quercus ilex) and a herb (Tolpis barbata). An immediate depletion of 2-4 per thousand from the initial delta(13)C(res) value occurred during the first 30 min of darkening. Q. ilex exhibited further a substantial diurnal enrichment in delta(13)C(res) of 8 per thousand, followed by a progressive depletion during the night. In contrast, T. barbata did not exhibit a distinct diurnal pattern. This is in accordance with recent theory on fractionation in metabolic pathways and may be related to the different utilisation of the respiratory substrate in the fast-growing herb and the evergreen oak. These data indicate substantial and rapid dynamics (within minutes to hours) in delta(13)C(res), which differed between species and probably the growth status of the plant. The in-tube incubation method enables both high time-resolved analysis and extensive sampling across different organs, species and functional types. PMID- 17348088 TI - Direct mass spectrometric analysis of flavors and fragrances in real applications using DART. AB - DART (Direct Analysis in Real Time) is an innovative technology to analyze complex solid samples at atmospheric pressure and ground potential by simply placing them between a DART ion source and a mass spectrometer. The analytes are ionized by a gun of neutral metastable species. The first examples of the application of DART to the analysis of flavor and fragrance raw materials in real, complex applications are reported here. A remarkably high potential of the technique is demonstrated. DART was applied to semi-quantitative analyses of perfumery raw materials deposited on smelling strips. In optimal cases, limits of detection around 100 pg were achieved. DART also allowed the assessment of the deposition and release of fragrance on surfaces such as fabric and hair. Finally, DART permitted the screening of twelve chewing gum samples for the possible presence of taste-refreshing compounds in less than 30 min. PMID- 17348089 TI - The motion: large BPH should be treated by open surgery. PMID- 17348090 TI - The more the merrier. By Caveman. PMID- 17348091 TI - Interferon. Alive and well. PMID- 17348093 TI - Influenza in the world. September 2006 - January 2007. PMID- 17348092 TI - Suffering from success: ASC buy-in issues and fair market value. PMID- 17348094 TI - Risk of epidemic meningitis in Africa: a cause for concern. PMID- 17348095 TI - Vaccination against human papillomavirus. PMID- 17348096 TI - Escitalopram oxalate: co-existence of oxalate dianions and oxalic acid molecules in the same crystal. PMID- 17348097 TI - Abstracts of an International Symposium on Recent Advances in Endemic Nephropathy: The Role of Toxins in an Environmental Disease. PMID- 17348098 TI - [Abstracts of the 100th French Urology Congress, 29 November-2 December 2006, Paris, France]. PMID- 17348099 TI - Abstracts from the 3rd World Congress of the World Association of Reproductive Medicine, 27 September-1 October 2006, Rome, Italy. PMID- 17348100 TI - Abstracts of the XVIII Annual Meeting of the Latin-American Society of Pediatric Endocrinology(SLEP), September 30-October 3, 2006, Vina del Mar, Chile. PMID- 17348101 TI - 2006 Society for Leukocyte Biology list of members. PMID- 17348102 TI - 2006 International Endotoxin and Innate Immunity Society list of members. PMID- 17348104 TI - [Abstracts of the 8th Argentine Congress of Virology, 19-22 September 2005]. PMID- 17348103 TI - Abstracts of the joint meeting of the Society for Leukocyte Biology and the International Endotoxin and Innate Immunity Society, November 9-11, 2006, San Antonio, Texas, USA. PMID- 17348105 TI - Margaret Chan named as new Director-General of WHO. PMID- 17348106 TI - NICE taken to task over unfair decisions. PMID- 17348107 TI - Are we doing the right phase III trials? PMID- 17348108 TI - Intravenous iron improves treatment for anaemia. PMID- 17348109 TI - New guidelines for response in malignant lymphoma. PMID- 17348110 TI - Toxic effects in head and neck cancer treatment. PMID- 17348111 TI - [Francesco Cetti and the natural history of Sardinia]. PMID- 17348112 TI - Combining treatments for superior sulcus NSCLC. PMID- 17348113 TI - Men with breast cancer have high risk of second cancer. PMID- 17348114 TI - Vote against blockade could help cancer treatment in Cuba. PMID- 17348115 TI - Fallon leukaemia cluster findings, research plans announced. PMID- 17348116 TI - Clinical Trials Directive slows registration of paediatric studies. PMID- 17348117 TI - Anterior apical biopsy helps prostate-cancer detection. PMID- 17348118 TI - New technique for detecting breast cancer. PMID- 17348119 TI - Topotecan more effective than supportive care. PMID- 17348120 TI - Familial pancreatic-cancer gene found. PMID- 17348121 TI - Adjuvant docetaxel-based treatment for breast cancer. PMID- 17348122 TI - Carcinogenicity of household solid fuel combustion and of high-temperature frying. PMID- 17348123 TI - Metabolic syndrome: why the controversy? AB - As originally conceived, the metabolic syndrome defined a clustering of cardiovascular disease risk factors with insulin resistance as the common, underlying pathophysiologic determinant. The definition of the syndrome has evolved since then, with several groups proposing somewhat differing definitions. Partly, this has been motivated by efforts to make the syndrome a clinically useful entity. However, recent articles have called the clinical use of the metabolic syndrome into question. In this review, some of these concerns and counterarguments for the continued use of the metabolic syndrome are reviewed. PMID- 17348124 TI - Plant volatiles: new perspectives for research in Brazil. AB - Agroecosystems consist on complex trophic relationships among host plants, herbivores and their natural enemies. This article reviews the research of plant volatiles in Brazil, in order to determine multiple resistance mechanisms of economically important crops and to contribute to the understanding of insect plant interactions. Most pest management programs, including chemical and biological control, do not consider the impact of these chemicals on herbivores and their natural enemies. Alternative control methods are being developed in order to improve our understanding on the endogenous mechanisms of plant induced defenses against phytophagous arthropods. The use of plant volatiles technology as an additional tool in integrated pest management programs would offer a new and environmentally sound approach to crop protection. This technique involves the development of baits that attract beneficial organisms and the manipulation of biochemical processes that induce and regulate plant defenses, key factors in the improvement of control programs against economically important pests. The elucidation of the mechanisms involved in the indirect defenses of plants will result in useful tools for biological control of crop pests. PMID- 17348125 TI - Foraging behavior of the queenless ant Dinoponera quadriceps Santschi (Hymenoptera: Formicidae). AB - The search for and ingestion of food are essential to all animals, which spend most of their lives looking for nutritional sources, more than other activities such as mating, intra-specific disputes or escaping from predators. The present study aims to describe and quantify several aspects of foraging behavior, diet and food transport in the queenless ant Dinoponera quadriceps Santschi in a secondary Atlantic forest, Northeastern Brazil. Three colonies were randomly selected at a distance of at least 50 m from one another. On leaving the colony, worker ants were followed until their return, with no nutritional provision or interference with their activities. Activities were recorded using focal time sampling with instantaneous recording every minute for 10 consecutive minutes. Each colony was observed 1 day/week, for at least 6 h/day resulting in 53.8h of direct observation of the workers. Foraging activities, success in transporting food, type of food, cleaning and interaction among the workers were recorded. Foraging was always individual, with no occurrence of recruitment. Diet was composed mainly of arthropods, mostly insects. The collection of small fruits (Eugenia sp.) was also observed. Foraging time was greater when workers transported food to the colony, the return time being shorter than the foraging period, suggesting the use of chemical and visual cues for orientation during their foraging and food-collecting activities. PMID- 17348126 TI - Diversity in bee (Hymenoptera: Apoidea) and social wasp (Hymenoptera: Vespidae, Polistinae) community in "campos rupestres", Bahia, Brazil. AB - Hymenoptera such as bees and social wasps are regular floral visitors in "campos rupestres" vegetation. A community of bees and social wasps was studied during floral visitation in an area of "campos rupestres", at Chapada Diamantina, BA, Brazil, from September 2001 to April 2002. The community was described in relation to diversity, evenness, and dominance rank, considering the individuals abundance (H' = 2.14/ J' = 0.55) and biomass (H' = 2.34/ J' = 0.60). Thirty nine bee (588 individuals/ 15.742 g) and 11 social wasp species (52 individuals/ 2.156 g) were collected, being the first report of social wasps for the Brazilian "campos rupestres". The main species regarding number of individuals were Trigona spinipes (Fabricius), Apis mellifera L., Frieseomelitta francoi (Moure), and Bombus brevivillus Franklin. About 48% of the species were represented by a single individual. There was an inversion in the dominance rank when the species biomass was considered. B. brevivillus, A. mellifera, T spinipes, and other species represented by 15 individuals or less, such as the social wasps Synoeca cyanea (Olivier), Polistes canadensis (L.) and Myschocyttarus drewseni (Saussure), and the bees Eufriesea nigrohirta (Friese), Xylocopa grisescens Lepeletier and Megachile (Pseudocentron) sp.l were the predominant species. The use of biomass in diversity analysis permitted to detect differences in the relative contribution of species in hierarchy dominance. The comparison between bee faunas from different areas indicates a large similarity of the sampled fauna in Palmeiras (Bahia State) with neighboring ecosystems, although with low values of similarity. PMID- 17348127 TI - Geographical distribution of genetically determined types of Nezara viridula (L.) (Heteroptera: Pentatomidae) in Brazil. AB - Nezara viridula (L.) is a cosmopolitan and polymorphic pentatomid. Several genetically determined types have been described due to body color variation in adults. A survey covering 13 Brazilian states was conducted during 2001 and 2002 to determine the geographical distribution of the main types. Type G (smaragdula- body entirely green), the most common, showed a wide distribution, from south to north (latitude 2 degrees 49' N to 31 degrees 46' S), except in the Central-West Region. Type O (torquata--body green with lateral and median lobes of the head and anterior margin of the pronotum yellow), less abundant than the former, was more frequent at latitudes > 23 degrees 18' S and mean annual temperatures < 20.8 degrees C (Southern Region). Type Y (aurantiaca--body entirely gold or orange), which is rare, was collected only in the Southern Region. N. viridula (smaragdula) was captured in only one place in the Northern Region (Boa Vista, RR, latitude 2 degree 49' N). The abundance of the two most common types, smaragdula and torquata, was not correlated with altitude. PMID- 17348128 TI - [Folivore caterpillars on Roupala montana Aubl. (Proteaceae) in cerrado sensu stricto]. AB - Richness of lepidopteran species in the cerrado is high. The confirmation of this richness is based on adult records but knowledge of larvae-host plants interactions is still incipient. The main purpose of this work was to identify folivorous caterpillar species on Roupala montana Aubl. in areas of a Brazilian cerrado sensu stricto, their dietary range, and the relative age of the consumed leaves richness. Three data sets, collected from 1991 to 2004 were used in this study. All caterpillars found on the host plants in the field were collected and reared in the laboratory. Sixty-two lepidopteran species from 22 families were recorded; they were found feeding on new (8%) and mature (92%) leaves of R. montana. Cerconota sciaphilina (Zeller) (Elachistidae), two unidentified Gracillariidae species and, one species of Gelechiidae fed only on new leaves. These species showed a short life cycle, which was very syncronized with the host plant foliar phenology. Among the species feeding on mature leaves, 36 were considered polyphagous and, these showed a large variation in the use of the food resource. Twenty-six species were found only on R. montana, 58% were very rare, a character that difficults the analysis of their dietary range. The monophagous species on R. montana were: Chlamydastisplatyspora (Meyrick) (Elachistidae), Stenoma cathosiota Meyrick (Elachistidae), Idalus prop. sublineata (Rothschild) (Arctiidae), and Eomichla sp. (Oecophoridae). PMID- 17348129 TI - Effect of nitrogen on Passiflora suberosa L. (Passifloraceae) and consequences for larval performance and oviposition in Heliconius erato phyllis (Fabricius) (Lepidoptera: Nymphalidae). AB - The present study examines the influence of nitrogen on growth rates, morphological and nutritional characteristics of Passiflora suberosa L., and the corresponding consequences for Heliconius erato phyllis (Fabricius) growth and oviposition. The treatments consisted of different nitrogen doses (0, 150 and 300 mg L(-1)) applied to the soil. Newly emerged larvae were individually reared in the laboratory (25+/-1 degree C) on branches of P. suberosa obtained from plants grown under the three nitrogen levels, and field collected females were submitted to oviposition choice tests. P. suberosa growth rates, leaf area and internode length increased significantly when grown with nitrogen enriched soil. P. suberosa presented significantly greater leaf toughness when grown without nitrogen addition. Leaves of this species also presented lower water content and toughness. Nitrogen addition increased the concentration of nitrogen and potassium on plant leaf tissues. The greater nitrogen concentration on plants did not affect H. erato phyllis larval survival, but led to a reduction in larval development time and increased adult size. Females significantly preferred to lay eggs in plants cultivated in nitrogen enriched soil. This choice was positively correlated with larval performance, which could be a possible explanation for the maintenance of that behaviour, as well as the choice of larger branches as reported in previous studies. PMID- 17348130 TI - RAPD variation within and among species of Melittobia westwood (Hymenoptera: Eulophidae). AB - The genus Melittobia Westwood comprises several species of microparasitoids and only two of them are know to occur in Brazil up to now: M. australica Girault and M. hawaiiensis Perkins. Nevertheless, the differentiation between these two species using traditional taxonomy is very difficult. In the present study, we used random amplified polymorphic DNA chain reaction (RAPD-PCR) to test for its ability to discriminate between these two species and to examine the genetic variation among the studied populations of M. australica. Most of the generated fragments were species-specific, occurring in all individuals of one species and absent in the individuals of the other species demonstrating the appropriateness of such technique to distinguish between both of the Melittobia species occurring in Brazil. RAPD-PCR also demonstrated low variability among different populations of M. australica, which may be due to a founder effect and/or high dispersion capacity of these populations. Genetic distances within (D = 1.19-3.54%) and among populations (D = 1.93-5.28%) presented very low values, reflecting the reduced genetic variation that exists among populations of M. australica. PMID- 17348131 TI - Euglossa anodorhynchi sp. n. (Hymenoptera: Apidae), a new orchid bee from southern Brazil. PMID- 17348132 TI - [Relation between the size of the acid gland and the quantity of venom produced in Africanized bee, Apis mellifera L. (Hymenoptera: Apidae), in the region of Dourados, MS, Brazil]. AB - Crosses between African and European honeybees in Brazil resulted in a highly defensive hybrid bee. The acid gland is important in the expression of this characteristic, being responsible for venom production. Morphological variations in this gland could influence the quantity of venom. Glandular morphology was analyzed, along with the quantity of venom produced and the bees' genetic characteristics. The gland and the venom reservoir were removed from workers. The gland was placed on a histological frame for measurement and the contents of the reservoir were weighed. The results were submitted to an analysis of regression and submitted to Test Z, to evaluate the differences between the averages. The phenotypes were evaluated according to the standard found in literature. Gland length varied from 7.42 mm to 20.33 mm, the quantity of venom from 0.19 mg to 0.34 mg, and as far as the genetic characteristics are concerned, 63.3% of the colonies had workers with large glands. In 53.3% of the colonies, 90% of individuals had simple glands, suggesting the evolutionary process leading to the loss of branching, since the presence of branching indicates primitiveness. The production of venom is associated with the length of the gland and branching does not influence the quantity of venom. There was no statistical difference between the size of the branched and simple glands or in the quantity of venom produced, therefore the large glands can favor commercial exploration of venom, producing larger quantities. PMID- 17348133 TI - Biological, nutritional, and histochemical basis for improving an artificial diet for Bracon hebetor Say (Hymenoptera: Braconidae). AB - The biology of Bracon hebetor Say (Hymenoptera: Braconidae) reared on fifth instars of Anagasta kuehniella (Zeller) (Lepidoptera: Pyralidae) (natural diet) and in vitro (artificial diet) was evaluated. Data on the number of instars, development time and food intake were collected, and histochemical tests were conducted to detect proteins and lipids in the parasitoid's digestive tract. The data disclosed differences that can help to improve artificial rearing of B. hebetor. B. hebetor had three instars in both diets, but the developmental time on the artificial diets was prolonged due to the increase in larval and pupal development times. Larvae grew faster on the natural host and required a lower food intake (2.7 microl) as compared to that required by the larvae feeding on the artificial diet (3.8 microl). Analysis of diet protein content and host hemolymph and the observations on the parasitoid larvae gut content indicated altogether the artificial diets requires the addition of others sources of proteins and lipids to improve the overall nutrition quality of the in vitro rearing system for this ectoparasitoid. PMID- 17348134 TI - [Susceptibility of Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae) adults to fungicides used to control apple diseases]. AB - This study evaluated the susceptibility under laboratory conditions of Trichogrammapretiosum Riley adults to fungicides recommended by the Integrated Production of Apple (IPA). The bioassays were carried out using the International Organization for Biological Control (IOBC), West Palearctic Regional Section (WPRS) standard protocols. Twelve selected fungicides were studied in the doses (g or ml active ingredient/100 L) captan 1 (0.115), captan 2 (0.120), kresoxim methyl (0.010), sulphur 1 (AG) (0.480), sulphur 2 (0.480), folpet (0.105), mancozeb (0.160), pyraclostrobin (0.010), tebuconazole (0.010), tetraconazole (0.005), thiophanate-methyl (0.050) and triforine (0.024). Distilled water was used as the blank treatment and the insecticide triclorfon (0.150) as a positive control. The parasitoids were exposed to dry residues applied on glass plates. The reduction in the capacity of parasitism was used to measure the effect of the chemical in comparison to the blank treatment. Each treatment was replicated four times. The results allowed us to classify the fungicides tested in four categories: 1, harmless (< 30%); 2, slightly harmful (30-79%); 3, moderately harmful (80-99%); and 4, harmful (> 99%). 75% of the tested substances were classified as selective (classes 1 and 2) to the parasitoid. The fungicides captan 1, captan 2, kresoxim-methyl, folpet, pyraclostrobin, tebuconazole, thiophanate-methyl and triforine were harmless; mancozeb was slightly harmful; sulphur 1 (AG) and tetraconazole were moderately harmful and sulphur 2 was harmful. These findings should be taken into account when selecting fungicides to spray apple orchards against fungi diseases to preserve the egg parasitoid T. pretiosum. PMID- 17348135 TI - [Selection of Beauveria bassiana (Bals.) Vuill. and Metarhizium anisopliae (Metsch.) Sorok. isolates against Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae)]. AB - This study was carried out to evaluate entomopathogenic fungi isolates as microbial control agents ofthe lesser mealworm, Alphitobius diaperinus (Panzer). Larvae and adults were inoculated with conidial suspension of 99 isolates of Beauveria bassiana (Bals.) Vuill. and Metarhizium anisopliae (Metsch.) Sorok. (10(5) to 10(9) conidia/ml). Vegetative growth on culture media and sporulation on culture media, cooked rice and lesser mealworm cadavers were also evaluated. Isolates of B. bassiana were more effective than the M. anisopliae isolates and larvae were more susceptible than adults. The isolates UNIOESTE 04 and UNIOESTE 02 were originally obtained from adults of the lesser mealworm and were the most efficient isolates. In addition, UNIOESTE 04 showed high level of sporulation on different culture media and is considered a potential useful tool to lesser mealworm control. PMID- 17348136 TI - [Interaction of Metarhizium anisopliae (Metsch.) Sorok., Beauveria bassiana (Bals.) Vuill. and the parasitoid Oomyzus sokolowskii (Kurdjumov) (Hymenoptera: Eulophidae) with larvae of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae)]. AB - Chemical insecticides are broadly applied to control diamondback moth, Plutella xylostella (L.). Diamondback moth is a major pest of cruciferous worldwide, and resistance of this pest to insecticide has been often reported. Thus, this research investigated the interactions among the fungi Metarhizium anisopliae (Metsch.) Sorok., Beauveria bassiana (Bals.) Vuill., and the larval-pupal parasitoid Oomyzus sokolowskii (Kurdjumov) before and after application of the fungi on DBM larvae offered to the parasitoid. The experiment was carried out at 26+/-l degreeC, 75+/- 5% RH and 12h photophase using a completely randomized design, with eight treatments with six replications each. The isolates E9 of M. anisopliae and ESALQ 447 of B. bassiana, were used at the concentration of 10(7) conidia ml(-1). The results showed that M. anisopliae and B. bassiana reduced the parasitism of P. xylostella by O. sokolowskii. Additive effects were found on the mortality of P. xylostella with the different combinations among the fungi and parasitoid, except for the treatment B. bassiana inoculated 24h before exposition of the larvae to O. sokolowskii. The isolates were more efficacious when applied after exposition of the larvae to the parasitoid. The efficiency of O. sokolowskii was negatively influenced by the presence of the fungi, mainly when the fungi were applied 24h before diamondback's larvae were exposed to the parasitoid. The association of the fungi with the parasitoid presents potential to be tested in field. The use of these natural enemies in the integrated management of P. xylostella may economically improve the cabbage productive system, especially for organic farming. PMID- 17348137 TI - [Fitness cost associated with carbosulfan resistance in Aphis gossypii Glover (Hemiptera: Aphididae)]. AB - In order to collect basic information for a resistance management program of Aphis gossypii Glover to carbosulfan, studies to evaluate fitness costs associated to this resistance were conducted under laboratory conditions. For this purpose, we studied the stability of carbosulfan resistance in A. gossypii populations with differing initial frequencies of resistance and compared life history traits of carbosulfan-susceptible and resistant strains. The stability of resistance was followed in three populations with initial frequencies of 20, 50 and 80% of resistant individuals. The susceptibility to carbosulfan was monthly estimated by using the diagnostic concentration of 32 ppm. The biology of carbosulfan-susceptible and resistant strains was evaluated in cotton plants kept under controlled climatic conditions. The resistance to carbosulfan was unstable, that is, there was a significant increase in the susceptibility of different populations of A. gossypii to this insecticide in the absence of selection pressure. Comparison of biological traits between carbosulfan-susceptible and resistant strains showed that there is a fitness cost associated with resistance. The resistant strain showed lower fecundity, shorter reproductive period and lower longevity than the susceptible strain. The net reproductive rate (Ro) was 14.04 and 43.18 and the finite rate of increase (lambda) was 1.25 and 1.30 females/female/day for the resistant and susceptible strains respectively. Therefore, the instability of carbosulfan resistance in A. gossypii can be exploited in resistance management programs. PMID- 17348138 TI - [Effect of the time of inoculation of the cotton vein mosaic virus by Aphis gossypii Glover (Hemiptera: Aphididae) on growth and yield of cotton plants]. AB - Aphis gossypii Glover is the vector of the Cotton Vein Mosaic Virus (CVMV), which causes serious damages to cotton. This work was carried out in a greenhouse at UNESP - Universidade Estadual Paulista, in Jaboticabal, Sao Paulo State, Brazil, to evaluate the effect of inoculation date of the CVMV on growth and yield of cotton plants. Cotton plants of cultivar CNPA ITA 90 at 20, 27, 34, 41, 48 and 55 days after the emergency (DAE) received one wingless viruliferous adult of A. gossypii, which remained confined in the plants for 48h. The percentage of plants with the symptoms of the disease and its influence in the phenological aspects of cotton plant were evaluated. The age of the plants did not influence the transmission efficiency of CVMV by A. gossypii. Percentages of plants showing disease symptoms varied from 40% to 65% when inoculated at 20 and 48 DAE, respectively. Plant height was reduced in 54.5% when they were infected 20 DAE and 1.3% when infection occurred at 55 DAE, as compared to the control. The number and diameter of the bolls were also influenced by the age the plants were infected. Plants inoculated 20 DAE did not produce cotton. Plants inoculated 55 DAE produced 20.7 g of cotton/plant, significantly less than control plants (35.9 g/plant). The severity of the symptoms was directly associated to the age the plants were infected with CVMV. PMID- 17348140 TI - [Biological efficacy and persistence of biphenthrin sprayed on maize at different grain temperatures]. AB - The objective of this work was to evaluate the immediate and latent effects of the grain temperature, during the spraying process, on the persistence and biological efficacy of the biphenthrin insecticide against Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae) and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). For such, biphenthrin was sprayed on the grain at the temperatures: 25, 30, 35, 40 and 45 degrees C. To access the persistence of biphenthrin, insecticide residue analyses were carried out monthly, just after spraying until 90 days of storage. To evaluate the biological efficacy of biphenthrin, 20 adults of each species were placed in petri dishes with sprayed grain, and kept in climate cabinets under 27 degrees C and 55% of RH, during 48h. Evaluations were done every 15 days, starting just after spraying and finishing at 90 days of storage. Both persistence and biological efficacy of biphenthrin reduced as storage time and grain temperatures increased. Additionally, S. zeamais was more tolerant to biphenthrin than T. castaneum. PMID- 17348139 TI - [Residues of thiamethoxam, aldicarb and its metabolites in coffee leaves and effect on the control of Leucoptera coffeella (Guerin-Meneville) (Lepidoptera: Lyonetiidae)]. AB - The coffee leaf miner Leucoptera coffeella (Guerin-Meneville), one of the major pests of coffee crops in Brazil, is mainly controlled with insecticides. The objective of this study was to evaluate the residues and the translocation of the insecticide thiamethoxam in coffee leaves, as well as to study its effect on the coffee leaf miner control, comparing it with aldicarb, used as standard. One experiment was set up in the county of Garca, SP from December/2001 to August/2002. The treatments used were: aldicarb 150 G at the rates of 2.25 and 4.50 g a.i./pit, thiamethoxam 10 GR, at the rates of 0.15 and 0.30 g a.i./pit and check. Twig samples were collected prior to and 30 , 60, 90, 120, 150, 180, 210 and 240 days after the application, at three coffee plant heights (lower, middle and upper third), and the percentage of mined leaves was evaluated. The determination of aldicarb residues, including their sulphoxide and sulfone metabolites and of thiamethoxam were performed by gas chromatography with a nitrogen-phosphorus and mass spectrometer detectors, respectively. The results indicated a uniform translocation of both insecticides in all three thirds of the coffee plants when applied to the soil. A higher persistence of thiamethoxam was verified with its residues being found for as far long as eight months following the application, while aldicarb residues, including the sulphoxide and sulfone metabolites, were found only until four to six months after the application. Control of the coffee leaf miner was observed with both insecticides. PMID- 17348141 TI - [Use of neem extract in the control of acariasis by Myobia musculi Schranck (Acari: Miobidae) and Myocoptes musculinus Koch (Acari: Listrophoridae) in mice (Mus musculus var. albina L.)]. AB - The objective of this work was to evaluate the acaricide action of neem extract formulated as a pomatum in the treatment of acariasis in mice (Mus musculus var. albina L.) naturally infected by Myobia musculi Schranck and Myocoptes musculinus Koch. Twenty parasitized animals were chosen and distributed in four groups: control (vaseline), 5%, 10% and 20% of neem. The animals were treated at 48h intervals and maintained in cages with food and water ad libitum and accompanied daily for 24 days. There was a decrease in the mean number of mites recovered after 96h with 5% of neem when compared to de others concentrations (P < 0.05). From 120h on, the concentrations of 10% and 20% were also efficient and differed statistically from the control group (P < 0.05 and P < 0.01; respectively). From 168h on, the animals treated with neem concentrations of 10% and 20% showed significant results (P < 0.01). The animals exhibit signs of hair recuperation and the mites were not observed anymore. After 216h, the hair was completely recovered and the animals remained free of the infestation in the concentrations of 10% and 20%. The neem pomatum showed acaricide action in the concentrations of 10% and 20% for mice and when used as a topical remedy, had good phlogistic and cicatrizing activity and showed no side effects. PMID- 17348142 TI - Natural efficiency of parasitism by Billaea rhynchophorae (Blanchard) (Diptera: Tachinidae) for the control of Rhynchophorus palmarum (L.) (Coleoptera: Curculionidae). AB - The occurrence of the tachinid parasitoid Billaea rhynchophorae (Blanchard) on larvae of the palm weevil Rhynchophorus palmarum (L.) was evaluated in plantations of piassava palm (Attalea funifera Mart.) and African oil palm (Elaeis guineensis Jacquin), in southeastern Bahia, Brazil. The monthly percentages of parasitism were evaluated during 13 months, from November 2000 to November 2001, based on the comparison between the number of parasitized and non parasitized cocoons of R. palmarum. Mean parasitism was 40% and ranged from 50% in November 2000 to 18% in July 2001. While there is no method of mass reproduction of the parasitoid, a simple management practice is recommended, in order to preserve its beneficial effects in palm plantations. PMID- 17348143 TI - [Occurrence of Lysiphlebus testaceipes (Cresson) (Hymenoptera: Aphidiidae) on aphids (Hemiptera: Aphididae) in wheat plantation in Medianeira, Parana State, Brazil]. AB - This paper records the occurrence of Lysiphlebus testaceipes (Cresson) attacking aphids in wheat plantation in Medianeira, in the west region of Parana State, Brazil. This microhymenoptera was introduced and released by Embrapa Trigo, from 1978 to 1992 in the wheat production region at the state of Rio Grande do Sul, what suggests that individuals of this species may show high dispersal ability. PMID- 17348144 TI - Polyandrous behavior in Cerconota anonella Sepp (Lepidoptera: Oecophoridae). AB - Among insects polyandrous behavior is common and plays an important role in female reproductive output. The present study aimed to evaluate the mating frequency of the moth Cerconota anonella Sepp under laboratory conditions and to verify if polyandrous behavior is common in this species. Approximately 47% of females mated more than once. However they presented differences in the mating period (early or late). In general, precocious females were more frequent than late females (P < 0.001, Binomial test). Such results suggest that polyandry in C. anonella may be common in the field. PMID- 17348145 TI - Potential use of antibiotic to improve performance of laboratory-reared Nezara viridula (L.) (Heteroptera: Pentatomidae). AB - The antibiotic streptomycin added to the drinking water at a concentration of 125 mg/ l during nymphal development of Nezara viridula (L.) (Heteroptera: Pentatomidae)accelerated the development in ca. 2 days, increased survivorship, and doubled adult longevity; nymph survivorship and adult body weight were not affected when compared to control insects. Streptomycin has potential in rearing N. viridula, especially in improving quality of field-collected adults, by mitigating the introduction of pathogenic bacteria, and improving the quality of the population. PMID- 17348146 TI - [New records of Neosilba species (Diptera: Lonchaeidae) in Bahia State, Brazil]. AB - Four species of Neosilba are recorded in the State of Bahia: Neosilba pendula (Bezzi), Neosilba certa (Walker), Neosilba parva (Hennig) and Neosilba glaberrima (Wiedemann). PMID- 17348147 TI - The beef with cloned meat. PMID- 17348148 TI - Sight for sore eyes. Progress in cell transplants to heal damaged retinas. PMID- 17348149 TI - Alone at the top. Closer to God: Fermilab makes solo top quarks. PMID- 17348150 TI - Deadly dialogue. Healthy tissue may inadvertently call in tumors. PMID- 17348151 TI - Pole positions. The International Polar Year kicks off. PMID- 17348152 TI - Sympathy for the devil. Ideas emerge to save the dying Tasmanian devil. PMID- 17348153 TI - Scoring your identity. New tactics root out the false use of personal data. PMID- 17348154 TI - Breaking the mold. A real family value: mothers who work outside the home. PMID- 17348155 TI - (Can't get no) satisfaction. The new science of happiness needs some historical perspective. PMID- 17348156 TI - Threats of war, chances for peace. Preventing the spread of war will depend on strategies that recognize the shared interests of adversaries. PMID- 17348157 TI - Graph theory and teatime. Deep in the heart of Microsoft, Jennifer Chayes and Christian Borgs lead a who's who of mathematics and computer science. The goal? To explore anything they please. PMID- 17348158 TI - Black hole blowback. A single hole, samller than the solar system, can control the destiny of an entire. PMID- 17348159 TI - Mapping the cancer genome. Pinpointing the genes involved in cancer will help chart a new course across the complex landscape of human malignancies. PMID- 17348160 TI - A digital life. New systems may allow people to record everything they see and hear--and even things they cannot sense--and to store all these data in a personal digital archive. PMID- 17348161 TI - Down go the dams. Many dams are being torn down these days, allowing rivers and the ecosystems they support to rebound. But ecological risks abound as well. Can they be averted? PMID- 17348162 TI - New predictors of disease. Molecules called predictive autoantibodies appear in the blood years before people show symptoms of various disorders. Tests that detected these molecules could warn of the need to take preventive action. PMID- 17348163 TI - Diesels come clean. Improved engines and exhaust scrubbers, combined with a new fuel, will make energy-efficient diesels nearly as green as hybrids. PMID- 17348165 TI - Restoring flow. Left ventricular assist devices. PMID- 17348164 TI - Illusory color & the brain. Novel illusions suggest that the brain does not separate perception of color from perception of form and depth. PMID- 17348166 TI - Ask the experts. Do the virtual particles in quantum mechanics really exist? PMID- 17348167 TI - Men & depression. Facing darkness. PMID- 17348168 TI - I never knew what to expect. PMID- 17348169 TI - The ethical mind. A conversation with psychologist Howard Gardner. AB - Business leadership has become synonymous in the public eye with unethical behavior. Widespread scandals, massive layoffs, and inflated executive pay packages have led many to believe that corporate wrongdoing is the status quo. That's why it's more important than ever that those at the top mend relationships with customers, employees, and other stakeholders. Professor Gardner has spent many years studying the relationship between psychology and ethics at Harvard's Graduate School of Education. In this interview with HBR senior editor Bronwyn Fryer, Gardner talks about what he calls the ethical mind, which helps individuals aspire to do good work that matters to their colleagues, companies, and society in general. In an era when workers are overwhelmed by too much information and feel pressured to win at all costs, Gardner believes, it's easy to lose one's way. What's more, employees look to leaders for cues as to what's appropriate and what's not. So if you're a leader, what's the best way to stand up to ethical pressures and set a good example? First and foremost, says Gardner, you must believe that retaining an ethical compass is essential to the health of your organization. Then you must state your ethical beliefs and stick to them. You should also test yourself rigorously to make sure you're adhering to your values, take time to reflect on your beliefs, find multiple mentors who aren't afraid to speak truth to your power, and confront others' egregious behavior as soon as it arises. In the end, Gardner believes, the world hangs in the balance between right and wrong, good and bad, success and disaster. "You need to decide which side you're on:" he concludes, "and do the right thing." PMID- 17348170 TI - Managing differences: the central challenge of global strategy. AB - The main goal of any international strategy should be to manage the large differences that arise at the borders of markets. Yet executives often fail to exploit market and production discrepancies, focusing instead on the tensions between standardization and localization. In this article, Pankaj Ghemawat presents a new framework that encompasses all three effective responses to the challenges of globalization. He calls it the AAA Triangle. The A's stand for the three distinct types of international strategy. Through adaptation, companies seek to boost revenues and market share by maximizing their local relevance. Through aggregation, they attempt to deliver economies of scale by creating regional, or sometimes global, operations. And through arbitrage, they exploit disparities between national or regional markets, often by locating different parts of the supply chain in different places--for instance, call centers in India, factories in China, and retail shops in Western Europe. Ghemawat draws on several examples that illustrate how organizations use and balance these strategies and describes the trade-offs they make as they do so. Because most enterprises should draw from all three A's to some extent, the framework can be used to develop a summary scorecard indicating how well the company is globalizing. However, given the tensions among the strategies, it's not enough simply to tick off the corresponding boxes. Strategic choice requires some degree of prioritization--and the framework can help with that as well. While it is possible to make progress on all three strategies, companies usually must focus on one or two when trying to build competitive advantage. PMID- 17348171 TI - Leading clever people. AB - In an economy driven by ideas and intellectual know-how, top executives recognize the importance of employing smart, highly creative people. But if clever people have one defining characteristic, it's that they do not want to be led. So what is a leader to do? The authors conducted more than 100 interviews with leaders and their clever people at major organizations such as PricewaterhouseCoopers, Cisco Systems, Novartis, the BBC, and Roche. What they learned is that the psychological relationships effective leaders have with their clever people are very different from the ones they have with traditional followers. Those relationships can be shaped by seven characteristics that clever people share: They know their worth--and they know you have to employ them if you want their tacit skills. They are organizationally savvy and will seek the company context in which their interests are most generously funded. They ignore corporate hierarchy; although intellectual status is important to them, you can't lure them with promotions. They expect instant access to top management, and if they don't get it, they may think the organization doesn't take their work seriously. They are plugged into highly developed knowledge networks, which both increases their value and makes them more of a flight risk. They have a low boredom threshold, so you have to keep them challenged and committed. They won't thank you--even when you're leading them well. The trick is to act like a benevolent guardian: to grant them the respect and recognition they demand, protect them from organizational rules and politics, and give them room to pursue private efforts and even to fail. The payoff will be a flourishing crop of creative minds that will enrich your whole organization. PMID- 17348172 TI - Crisis at the summit. AB - An unrecognized affliction is striking certain gifted performers at the top of their game. Its cause, paradoxically, is success itself. These stars, who thrive on conquering new challenges, can lose their bearings and question their purpose once a job has been mastered. A vague dissatisfaction gives way to confusion and then to inner turmoil. Left unattended, this summit syndrome can derail promising careers. The syndrome has three phases. In the approach phase, when most of the challenges of a current job have been met, sufferers tend to push harder in a vain attempt to recapture the adrenaline rush of the climb. Then, in the plateauing phase, when virtually all the challenges have been conquered, these individuals, who are incapable of coasting, bear down to try to produce ever more stellar results, but to less effect and greater dissatisfaction. This leads to the terminal descending phase, when performance slips noticeably. As their superstar status fades, they jump ship, accept demotions, or take lateral transfers. It's a terrible waste, for if the syndrome is recognized, steps can be taken before performance slips to dispel the confusion and set the stage for productive growth to the next assignment. There are four parts to this process: First, understand your "winning formula"--the characteristic way you approach a situation--and the vital part it plays in feeling stale or losing your edge. Second, reconnect with your core purpose in life. Third, recast your current, or future, job to better align your inner aspirations with the external requirements of your work. And fourth, create a developmental path by honing a handful of core leadership competencies. None of this is easy, but for talented individuals--and the organizations that rely on them--the vaccine of preventive awareness is far better than gambling on an after-the-fact cure once the crisis is full-blown. PMID- 17348173 TI - Competitive advantage on a warming planet. AB - Whether you're in a traditional smokestack industry or a "clean" business like investment banking, your company will increasingly feel the effects of climate change. Even people skeptical about global warming's dangers are recognizing that, simply because so many others are concerned, the phenomenon has wide ranging implications. Investors already are discounting share prices of companies poorly positioned to compete in a warming world. Many businesses face higher raw material and energy costs as more and more governments enact policies placing a cost on emissions. Consumers are taking into account a company's environmental record when making purchasing decisions. There's also a burgeoning market in greenhouse gas emission allowances (the carbon market), with annual trading in these assets valued at tens of billions of dollars. Companies that manage and mitigate their exposure to the risks associated with climate change while seeking new opportunities for profit will generate a competitive advantage over rivals in a carbon-constrained future. This article offers a systematic approach to mapping and responding to climate change risks. According to Jonathan Lash and Fred Wellington of the World Resources Institute, an environmental think tank, the risks can be divided into six categories: regulatory (policies such as new emissions standards), products and technology (the development and marketing of climate-friendly products and services), litigation (lawsuits alleging environmental harm), reputational (how a company's environmental policies affect its brand), supply chain (potentially higher raw material and energy costs), and physical (such as an increase in the incidence of hurricanes). The authors propose a four-step process for responding to climate change risk: Quantify your company's carbon footprint; identify the risks and opportunities you face; adapt your business in response; and do it better than your competitors. PMID- 17348174 TI - What it means to work here. AB - What distinguishes a company that has deeply engaged and committed employees from another one that doesn't? It's not a certain compensation scheme or talent management practice. Instead, it's the ability to express to current and potential employees what makes the organization unique. Companies with highly engaged employees articulate their values and attributes through "signature experiences"--visible, distinctive elements of the work environment that send powerful messages about the organization's aspirations and about the skills, stamina, and commitment employees will need in order to succeed there. Whole Foods Market, for example, uses a team-based hiring and orientation process to convey to new employees the company's emphasis on collaboration and decentralization. At JetBlue, the reservation system is run by agents from their homes, a signature experience that boosts employees' satisfaction and productivity. Companies that successfully create and communicate signature experiences understand that not all workers want the same things. Indeed, employee preferences are an important but often overlooked factor in the war for talent. Firms that have engendered productive and engaged workforces address those preferences by following some general principles: They target potential employees as methodically as they target potential customers; they shape their signature experiences to address business needs; they identify and preserve their histories; they share stories--not just slogans--about life in the firm; they create processes consistent with their signature experiences; and they understand that they shouldn't try to be all things to all people. The best strategy for coming out ahead in the war for talent is not to scoop up everyone in sight but to attract the right people--those who are intrigued and excited by the environment the company offers and who will reward it with their loyalty. PMID- 17348175 TI - Maximizing your return on people. AB - Though most traditional HR performance metrics don't predict organizational performance, alternatives simply have not existed--until now. During the past ten years, researchers Laurie Bassi and Daniel McMurrer have worked to develop a system that allows executives to assess human capital management (HCM) and to use those metrics both to predict organizational performance and to guide organizations' investments in people. The new framework is based on a core set of HCM drivers that fall into five major categories: leadership practices, employee engagement, knowledge accessibility, workforce optimization, and organizational learning capacity. By employing rigorously designed surveys to score a company on the range of HCM practices across the five categories, it's possible to benchmark organizational HCM capabilities, identify HCM strengths and weaknesses, and link improvements or back-sliding in specific HCM practices with improvements or shortcomings in organizational performance. The process requires determining a "maturity" score for each practice, based on a scale of 1 (low) to 5 (high). Over time, evolving maturity scores from multiple surveys can reveal progress in each of the HCM practices and help a company decide where to focus improvement efforts that will have a direct impact on performance. The authors draw from their work with American Standard, South Carolina's Beaufort County School District, and a bevy of financial firms to show how improving HCM scores led to increased sales, safety, academic test scores, and stock returns. Bassi and McMurrer urge HR departments to move beyond the usual metrics and begin using HCM measurement tools to gauge how well people are managed and developed throughout the organization. In this new role, according to the authors, HR can take on strategic responsibility and ensure that superior human capital management becomes central to the organization's culture. PMID- 17348176 TI - Realizing what you're made of. AB - A ruptured disk pressed against Glenn Mangurian's spinal cord several years ago, leaving the lower half of his body permanently paralyzed. One minute, Mangurian was healthy and secure in his career as a management consultant; the next, his life was transformed and filled with uncertainty. The injury has taught him volumes about resilience and leadership. In this first-person account, he explains how people can create a new future after a crisis hits--and how, even if they're simply tackling everyday challenges, they can prepare themselves for the worst. Mangurian identifies resilience as one of the key qualities desired in business leaders today, but he says that many people confuse it with toughness. Toughness certainly can be an advantage in business, because it enables you to separate emotion from the negative consequences of difficult choices. But it can also be a disadvantage, because it can cut you off from many of the resources you'll need to bounce back after a crisis. Resilience, by contrast, is mostly about absorbing challenges--not deflecting them--and rebounding stronger than before. The author has learned a number of lessons about leadership in the face of adversity. For instance, although crisis distorts reality by reinforcing your fears, it also puts an emphasis on what matters right now; it highlights what's important to you and what you're capable of. Another major lesson is that loss amplifies the value of what remains, pushing you to take stock of what you have and to celebrate your assets. Perhaps most important, you can't know what will happen tomorrow--and it's better that way, because it's far more rewarding to engage with the present than just to prevent bad things from happening. PMID- 17348177 TI - Total, free, and percent free prostate-specific antigen levels among U.S. men, 2001-04. AB - OBJECTIVE: Screening for prostate cancer using prostate-specific antigen (PSA) tests is common but remains controversial. Total PSA using thresholds of 4.0 and 2.5 ng/mL has been used for screening men. In addition, the percent free PSA (free PSA/total PSA x 100%) using thresholds of less than 25% and 15% have been proposed for use in screening for prostate cancer in conjunction with the total PSA. The distributions of total PSA, free PSA, and percent free PSA, which vary with age and race-ethnicity among American men, would help determine the burden of screening using different thresholds of PSA tests. METHODS: PSA tests were performed on serum samples from men age 40 years and older (n = 2,546) who participated in the 2001-04 National Health and Nutrition Examination Survey (NHANES). Total, free and percent free PSA were estimated for Mexican American, non-Hispanic white, and non-Hispanic black men. RESULTS: About 6.2%, (95% confidence interval, 95% CI: 5.2-7.2%), corresponding to an estimated 3.6 million (95% CI: 3.0-4.2 million) men 40 years of age and older, had a total PSA of greater than or equal to 4.0 ng/mL. Approximately 3.6% (95% CI: 1.8-6.2%) of Mexican American men, 6.2% (95% CI: 5.1-7.6%) of non-Hispanic white men, and 7.8% (95% CI: 5.2-11.1 ) of non-Hispanic black men had total PSA of 4.0 ng/mL or more. Approximately 13.1 (95% CI: 11.7-14.5%) of men 40 years of age and older had total PSA greater than or equal to 2.5 ng/mL. For men with total PSA less than 2.5 ng/mL, 23.1% (95% CI: 21.0-25.3%) had a percent free PSA between 15% and 25%, and 5.0% had free PSA (95% CI: 3.9-6.4%) less than or equal to 15%. CONCLUSIONS: The effect of lowering the total PSA thresholds increases the number of U.S. men who would be referred for screening for prostate cancer. Total and free PSA increased with age in Mexican American, non-Hispanic white, and non-Hispanic black men. Information about the distribution of total, free, and percent free PSA will help guide public health policy in screening for prostate cancer. PMID- 17348178 TI - Employment-based health benefits: access and coverage, 1988-2005. PMID- 17348179 TI - [Multi-components quantitation by one marker new method for quality evaluation of Chinese herbal medicine]. AB - OBJECTIVE: To establish a new quality evaluation method for Chinese herbal medicine, using one chemical reference substance to calculate multi-components simultaneously. METHOD: Relative correction factors (RCF) of mutongsaponin B and C to saponin PJ1, a characteristic component as marker, were calcalated in The chromatographic conditions for determination of the three saponins in Caulis Akebiae akebiae as a research model. The contents of saponin PJ1 were determined by external standard method, and those of mutongsaponin B and C were calculated by saponin PJ1 and their RCF. The accuracy of the new method was evaluated by comparing the calculated contents with the determined contents. RESULT: The analysis procedures were validated. There has been no significant difference between the calculated contents and the determined contents, according to the angle cosine value, and the calcalated RCF have confidence value. CONCLUSION: The method of multi-components quantitation by one marker has been verified in caulis akebiae and it is to be a new quality evaluation pattern for Chinese herbal medicines. PMID- 17348180 TI - [Discussion on method of synthetic assessment for threaten and priority conservation of medicinal plants]. AB - According to the resource of medicinal plant's present situation and characteristic, we took the primary discussion on the method of synthetic assessment to the threat and priority conservation of medicinal plants, and constituted the corresponding system of synthetic assessment, regarding four aspects: coefficience of value, coefficience of distribution, coefficience of biology, coefficience of present situation, etc., and fifteen minor terms as standards. PMID- 17348181 TI - [Application of supercritical solution rapid expansion technology in preparation of fine pharmacal particles]. AB - Rapid expansion of supercritical solution (RESS), a new technology, has been developed in the recent years. Fundamental principle of RESS technology used to prepare fine pharmacal particles was summarized in this paper. A brief review of factors which influenced the process of RESS and application of RESS technology were introduced. PMID- 17348182 TI - [Genetic diversity of Coptis chinensis germplasm based on ISSR analysis]. AB - OBJECTIVE: To detemine the genetic diversity of Coptis chinensis. METHOD: 32 germplasmic resources of C. chinensis were analyzed by ISSR molecular markers. To make up the systematic diagram of genetic relationship by TREECONW software and clustered by UPGMA method. RESULT: A total of 106 ISSR bands were scored, among which 51 were polymorphic bands. The average percentage of polymorphic bands was 48. 1%. Genetic similarity coefficient were changed from 0. 825 8 to 0. 935 1. By cluster analysis, the geographical distribution is not very obvious, but it was also showed some of the C. chinensis from the same region were in the same group which presented the law of geographical distribution in the tested materials. CONCLUSION: Different germplasms diversity of C. chinensis is low and the relationship of C. chinensis is close. PMID- 17348183 TI - [Application of multiplex allele-specific PCR for authentication of Panax ginseng and P. quinquefolius]. AB - OBJECTIVE: Searching and identifying SNP in Panax species and using multiplex allele-specific PCR (MAS-PCR) to authenticate P. ginseng and P. quenquefolium. METHOD: Based on genbank database of Panax species, using DNAMAN to align the sequences, identify SNP of P. ginseng and P. quenquefolium. Design allele specific primers for P. ginseng and P. quenquefolium, optimize the PCR reaction system including the usage amount of Taq, dNTP, primer, etc. Optimized system was performed with the total DNA of 20 different sources of P. ginseng and P. quenquefolium. RESULT: When the annealing temperature was 66 'C, the template DNA of P. ginseng could be amplified 249 bp band whereas P. quenquefolium amplified 1 049 bp band. CONCLUSION: The MAS-PCR have the advantages of highly specific, good reproducibility and could be identify P. ginseng and P. quenquefolium in the same PCR tube. It was a potential method to use in the molecular identification of other meteria medica. PMID- 17348184 TI - [Studies on growth and intake law of Whitmania pigra with temperature]. AB - OBJECTIVE: To observe Whitmania pigra growth and intake law in different temperature conditions and patterns. METHOD: Comparison of W. pigra growth in different weight and different temperature conditions, and observe the intake law of W. pigra within 24 h. RESULT AND CONCLUSION: The appropriate temperature for W. pigra growth is 15 - 25 degrees C. Its largest weight of intake increas with the weight of W. pigra and temperature rise, but with the intake rate increase, individual intake reduced. W. pigra intake have the two peaks in 24 h. PMID- 17348185 TI - [Studies on using spray drying technique in preparing Ophiopogon japonicus saponin enteric microsphere by orthogonal experimental design]. AB - OBJECTIVE: To explore the best technique parameters on preparing ophiopogon japonicus saponin enteric microsphere by spray drying technique. METHOD: The best technique parameters were investigated by orthogonal experimental design and by the target, such as surface appearances, encapsulated efficiency, etc. RESULT: The best technique parameters included the inlet temperature (90 degrees C ), the feeding speed (10 mL x min(- 1)), and the rotate speed of atomizer (50 r x min( 1)). CONCLUSION: Ophiopogon japonicus saponin enteric microsphere accorded with the expecting demand. The main influencing factor was inlet temperature . It is suitable to industrialize in preparing Traditional Chinese Medicine microsphere. PMID- 17348186 TI - [Investigate into of effective constituent transference of herba Ephedrae and cortex Magnoliae officinalis in preparation course of Shujin Kechuan capsule]. AB - OBJECTIVE: Investigate into transport rate and retention rate transference of principal effective constituent in Shujin Kechuang capsule, a new development Chinese patent medicine for theraphy asthma. METHOD: HPLC was applied to analyze the content of ephedrine hydrochloride and honokiol and magnolol in crude drugs and 60% ethanol extracting solution and 25% concentrated solution,50% concentrated solution, 100% concentrated solution and finished product ( Shujin Kechuang capsule). RESULT: The transport rate of ephedrine hydrochloride and honokiol and magnolol is 56. 32%, 14. 43%, 14. 56% in the finished product respectively. CONCLUSION: should be concentrate and desiccation in the condition that decompress and low temperature. PMID- 17348187 TI - [Chemical constitutents of Bauhinia aurea]. AB - OBJECTIVE: To study the chemical constituents of Bauhinia aurea. METHOD: The compounds were isolated with column chromatography. The structures were determined by MS and NMR spectroscopic techniques. RESULT: Nine aromatic acid derivatives, two triterpenes and three steroids were isolated from the 90% ethanolic extract and their structures were identified as 3,4-di-hydroxybenzoic acid (1), 4-hydroxybenzoic acid (2), 3-hydroxy-4-methoxy-benzoic acid (3), 4 hydroxy-3-methoxybenzoic acid (4) , gallic acid (5) , methyl gallate (6) , ethyl gallate (7) , lupeol (8) , lupenone (9) , stigmast4-en-3-one (10) beta-sitosterol (11) and daucosterol (12). CONCLUSION: This is the first report of chemical constituents from B. aurea. Compounds were isolated from this genus for the first time, except 5,8,11 and 12. PMID- 17348188 TI - [Studies on diterpenes in needles of Pinus sylvestris]. AB - OBJECTIVE: To research the constituents in needles of Pinus sylvestris. METHOD: Repeated column chromatography and preparation HPLC are used for compound isolation, and their structures were elucidated on the basis of spectral data analysis. RESULT: Six compounds, pinifolic acid (1), 15-oxo-8 (17) -labden-18-oic acid (2) , 15-acetoxy-labd-8 ( 17)-en-18-oic acid (3), dehydroabietic acid (4), 7alpha-hydroxydehydroabietic acid (5), 7beta-hydroxydehydroabietic acid (6) were isolated from the needles of P. sylvestris. CONCLUSION: Compound 3-6 were isolated from the needles of P. sylvestris for the first time, and compound 3 is a new natural product. The petroleum ether and EtOAc extracts showed significant cytotoxic effects to Hela and A549. Compounds 2, 4-6 revealed a positive distinction compared to the control group. PMID- 17348189 TI - [Studies on flavonoid constituents from herbs of Artemisia ordosica II]. AB - OBJECTIVE: To study the chemical constituents of herbs of Artemisia ordosica. METHOD: The chemical constituents were isolated and repeatedly purified on silica gel column and the structures were elucidated by the NMR spectra and physicochemical properties. RESULT: Eight flavones were obtained and they were identified as isosakuranetin, 7, 4'-dimethylaro madendrin, acacetin, cirsimaritin, rhamnetin, eupatolin, 5, 7, 2', 4'-tetrahydroxy-6, 5' dimethoxyflavone, hyperoside. CONCLUSION: All the compounds were obtained from herbs of A. ordosica for the first time. PMID- 17348190 TI - [Studies on chemical constituents from leaves of Isatis indigotica]. AB - OBJECTIVE: To study the chemical constituents of the leaves of Isatis indigotica. METHOD: The leaves of I. indigotica were extracted with 80% ethanol. The EtOH extract was dispersed in H20 and extracted with petroleum, EtOAc and BuOH successively. The EtOAc fraction was isolated and purified by column chromatography on silica gel, Sephadex LH -20 and Rp-8, Rp-18. All the compounds were identified on the basis of spectral analyses (including MS, 1H-NMR, 13 C NMR) , RESULT: Eleven compounds were isolated from the leaves of I. indigotica, and structures were characterized as 10H-indolo [3, 2-b] quinoline (1), indirubin (2), 4 (3H)-quinazo-linone (3), (E)-3-(3', 5'-dimethoxy-4'-hydroxybenzylidene) -2 indolinone (4), 2, 3-dihydropyrrolo [2, 1-b] quinazolin-9(1H) -one (5) , benzoic acid (6) , o-droxy-benzoic acid (7), ( - ) -lariciresinol (8) , ( + ) isolariciresinol (9), isovitexin (10), 6-f-D-glucopyranosyldiosmetin (11). CONCLUSION: 1, 4, 5, 8, 9, 11 were obtained from the leaves of I. indigotica for the first time. PMID- 17348191 TI - [Terpenoid compounds isolated from Ligularia sagitta]. AB - OBJECTIVE: To study the chemical constituents of radix and rhizome of Ligularia sagitta. METHOD: Isolation and purification were carried out on the column chromatography of silica gel and sephadex LH -20. The structures were identified by spectral analysis. RESULT: Seven terpenoid compounds were isolated from the radix and rhizome of L. sagitta. Five of them are sesquiterpenoids, the structures were determined as 7alpha-hydroxy-9(10) -ene-1, 8-dioxo-6, 7 dihydrofuranoeremophilane (1), 1p, 10P3-epoxy-6beta, 8 beta-dihydroxy-eremophil7 (11) -en-12, 8alpha-olide (2) , 1-oxo-9-desoxycacalol (3), benzofuranoeremophil-l ene (4) and bakkenolide (5); other two compounds belong to triterpenoid. 3p, 16P3 dihydroxy-12-oleanen-28-al (6) and lupeol (7). CONCLUSION: Compoundsl-3 and 6 were: isolated from L. sagitta for the first time, and compounds 3 and 6 were obtained from Ligularia for the first time. PMID- 17348192 TI - [Effects of corydyceps polysaccharide on liver fibrosis induced by DMN in rats]. AB - OBJECTIVE: To study the mechanism of Corydyceps polysaccharide (CP) actions against liver fibrosis. METHOD: SD rats were randomly divided into normal control group, DMN-induced liver fibrosis model group and CP treated group. Model group and CP group were injected intraperitonealy with 0. 5% dimethylnitrosamine (DMN) at dose of 2 mL x kg(-1) for 4 weeks to induce liver fibrosis. Then the later group was orally taken CP for 4 weeks. Liver tissue hydroxyproline (Hyp) content was determined by Jamall's method. The liver serum of ALT and AST activities, level of albumin and total bilirubin were analyzed The liver collagen deposition and were observed with Masson' collagen stains. In addition,the tissue inhibitor of metallprteinase-2 (TIMMP-2) level, metalloproteinade-2 (MMP-2) activity, type IV collagen content were observed. Liver samples were also analyzed malondiadehyde (MDA)level and superoxide dismutase (SOD) activity. RESULT: Compare with model group, CP improved the hepatic function (ALT, AST, Alb and Tbil). There were significant decreased of MDA content in CP group, SOD of CP group were markedly increased. Compared to those of normal control group, Hyp content, IV collagen content, TIMMP-2 level in liver tissue of model group increase significantly, and MMP-2 activity decreased, while CP decrees these pathological increase at different degrees. CONCLUSION: CP exerts rather good action against liver fibrosis, and with the mechanism relating to improve degradation of the deposited collagens and anti-lipid peroxiation. PMID- 17348193 TI - [Study on metabolism of tetramethylpyrazine in system of rat liver microsomes]. AB - OBJECTIVE: The metabolic character of tetramethylpyrazine (TMPz) in rat liver microsomes was studied in vitro and in vivo to identify which isoforms of cytochrome P450 were responsible for TMPz metabolism in rats, offer the theoretical foundation for the fact that it is rational to use medicine in clinic. METHOD: Set up UV- HPLC method of TMPz, determine concentration of TMPz and its formation in rat plasma and liver microsomes incubation solution, analyze the correlation between TMPz's metabolic eliminate rate and each inducer. Erythromycin( ERY) N-demethylase activity of each sample in rat liver microsomes was measured using N-demethylation reaction of ERY as probe. The correlation between the rate of TMPz metabolite formation and the demethylase activity was analysed. After the SD rats who had been treated with inducer, inhibitor, or untreated, received administration of TMPz in vein, the plasma concentration of TMPz were determined by HPLC. Pharmacokinetic parameters of TMPz were computed and compared. RESULT: The disppearing rate of TMPz in the incubation solutions of the rats liver microsomes, which treated with DEX, were markedly quicker than that of control group (P < 0. 01) , while no obvious difference between P-NF group or PB and control group was observed (P > 0. 05). The activity of ERY-N demethylase in DEX-induced group was corespondingly enhanced, was much higer than that in control group. The correlation between the rate of TMPz metabolic product formation and the activity of N-demethylase was significant. After using Ket, the CYP3A inhibitor, the metabolism of TMPz could be significantly inhibited the metabolism of TMPz in rat liver microsomes. In vivo, CL( s) were larger than that of the control group,t,/2 were smaller than the control group in DEX group; By contrary, CL(s) was smaller than the control group,t1/2 was larger than the control group in Ket group. CONCLUSION: Results suggest that CYP3A plays a major role in TMPz metabolism in rats, TMPz lie in the possibility of Interaction among the medicines between TMPz and CYP3A inducers or inhibitors when they are used in clinic. PMID- 17348194 TI - [Vasodilation effect of EUL on rat thoracic artery]. AB - OBJECTIVE: To observe vasodilation effect of EUL and its mechanism. METHOD: Isometric tension was recorded in isolated rat thoracic artery precontracted by noradrenaline (NE) to study the vasodilation effect of EUL, and to investigate the role of endothelial cell and vascular smooth muscle cell on vasodilation. RESULT: EUL was shown to significantly relax the endothelium-intact arteries precontracted by NE, relaxation had fall down on endothelium-denuded arteries. EUL did not affect the concentration-contraction curve of K+. NE and CaCl2 to shift to the right with an decrease in the maximum effective response, manifesting non-competitive antagonism (P <0. 01). The relaxant effect of EUL was significantly inhibited by pretreatment of endothelium-denuded aorta with potassium channel antagonist glibenclamide. CONCLUSION: EUL induces relaxation in rat aortic rings. The mechanisms may involve the endothelium and the activation of the potassium channels. PMID- 17348195 TI - [Protective effects of Xinnao Shutong capsule on acute cerebral ischemic injury of multiple infarcts in rats]. AB - OBJECTIVE: To study the effect of Xinnao Shutong capsule (XNST) on energy metabolism dysfunction, free radical injury and inflammatic factors in the course of acute cerebral ischemic damage, and try to reveal the mechanism of the protection against ischemia. METHOD: 60 male Wistar rats weighing 280 - 320 g were randomly divided into five groups: normal, sham operation, model, XNST treatment( XNST-T) , and Western medicine treatment (WM-T) group. Acute multi infarct model in rats was induced by injecting the embolus of blood powder through the right external carotid artery (ECA) into the internal carotid artery (ICA). At 72 hours after ischemia, morphologic change and the express of tumor necrosis factor-alpha (TNF-alpha) and interleukin -1beta ( IL-1beta) in hippocampus CAl section and cortex were observed, biochemical criterions including the activity of Na+ -K+ -ATPase, lactate dehydrogenase (LDH), superoxide dismutase (SOD), and the content of malondialdehyde (MDA) in hippocampus were examined. RESULT: The morphologic change of hippocampus and cortex in both XNST-T and WM-T groups was milder than that in model group. The activity of Na+ -K+ -ATPase, LDH and SOD in hippocampus were all significantly decreased in model group (P <0. 01), and elevated in XNST group (P <0. 01) as well as in WM-T group (P <0. 01). The content of MDA in hippocampus was significantly increased in model group (P <0. 05), and was reduced in XNST group (P <0. 05) as well as in WM-T group (P <0. 01). CONCLUSION: The results reveal that XNST has the protective effect against cerebral ischemic injury. And its possible mechanism is that XNST can prevent the upper pathological process. PMID- 17348196 TI - [Influence of Chinese herbal extract complex on expression of corticotropin releasing factor and protein kinasec protein in hippocampus of middle cerebral artery occlusion rats]. AB - OBJECTIVE: To explore the influence of one Chinese herbal extract complex (GETO) on the expression of corticotropin-releasing factor(CRF) and protein kinasec(PKC) proteins of the hippocampus in middle cerebral artery orilusion(MCAO) rats. METHOD: All rats were subjected to MCAO by nylon thread, except the sham-group rats. Rats were divied into four groups: sham-group, cerebral ischemia model group, GETO-group(6. 1 g x kg(-1) x d(-1) )and Duxil-group (7.3 mg x kg(-1) x d( 1)). Using immunohistochemistry technique we measured the expression quantity of CRF and PKC protein in hippocampus of MCAO rats at 2 h,6 h and 24 h after reperfusion, contrasted to Duxil. RESULT: CRF: There were lots of positive and deeper dyeing neurons in hippocampus of model-group rats, while there were a few of positive and lighter dyeing neurons in sham-group, GETO-group and Duxil-group. The positive expression areas of CRF protein in hippocampus of model-group was significantly bigger than that of sham-group, GETO -group and Duxil-group respectively( P <0. 01). PKC: There were a great number of denser positive granules in hippocampus of model-group rats, while there were a few of scattered positive granules in sham-group, GETO-group and Duxil-group. The positive expression areas of CRF protein in hippocampus of model-group was significantly bigger than that of sham-group, GETO-group and Duxil-group respectively( P < 0. 01). At the same time there was not significant difference about the expression of CRF and PKC protein between GETO group and Duxil-group. CONCLUSION: The high expression of CRF and PKC induced by cerebral ischemia may be one important factor that resulted in the delayed neuronal death in hippocampus. GETO can down regulate the expression of CRF and PKC induced by cerebral ischemia, which may be one of the mechanisms that the Chinese herbal extract complex, protect cerebral ischemic injury. PMID- 17348197 TI - [Comparative studies on purgative potency among three spieces of certified rhubarb]. AB - OBJECTIVE: To investigate the difference and causes of purgative activity in three species of certified rhubarb, so as to lay steady foundations of further research on assessing purgative activity impersonally by using measurable indexes. METHOD: The potencies of three species were comparied with purgative ED, of mice as quantitative index which were calculated, and activities of Na+ K + ATP ase in mouse colonic epithelial cell membrane were also investigated . The related purgative contents (conjunct and free rhein, chrysophanol, chrysophanic acid, sennoside A) were detected by HPLC and contents (total anthraquinones, anthraglucosennin; conjunct and free anthraquinones) were detected by UV. RESULT: There were different purgative activities among three spieces of certified rhubarb. Each purgative ED, of mice was Rheum tanguticum ( ED50 = 0. 37 g x kg ( 1)) , R. officinale ( ED50 = 0. 99 g x kg(-1) ) and R. palrnatum from Gansu (ED50 = 1. 83 g x kg(-1)) , the ratio of potency of those was 4. 94: 1. 85: 1. In the meanwhile, the difference of the inhibitory effect on Na+ -K + -ATP ase in mouse colonic epithelial cell membrane and relative purgative components also existed in the three species of certified rhubarb. CONCLUSION: It disclosed that there was notable diference of purgative activity and components among three spieces of certified Rhubarb, which probably resulted in the ultimate diference in clinical prescription and the production of Chinese patent medicines. PMID- 17348198 TI - [Research on Sailong boneextracts on proliferation and apoptosis of osteoblast cells]. AB - OBJECTIVE: To investigate the metabolic regulation and apoptosis of Sailong bone extracts on rat osteoblast cells in vitro. METHOD: Sailong bone fat-soluble extract, Sailong bone ethanol extract and Sailong bone aqueous extract were extracted with super critical fluid extraction (SCFE) , and Sailong bone boiling water component was extracted with distilled water directly. MTT assay was applied to determine the proliferation of the cell promoted by four Sailong bone extracts and PAS assay for the aqueous proportion of the cell at different doses. RESULT: Sailong bone fat-soluble and aqueous extract (each 10 mg x mL (-1)) could significantly improve the proliferation of rat osteoblast cells ROS 17/2. 8 (P < 0. 01). Compared with the blank, the proportion of xub-G, of the different extracts from Sailong bone is reduce evidently. The result have shown the extracts from Sailong bone could reduce the rate of aqueous of cell and could suspend the aqueous. CONCLUSION: Sailong bone can promoting the proliferation, degrading the rate of the apoptosis and delay the development of osteoblast to be the substitute of the bone of tiger as a Chinese materia medica. PMID- 17348199 TI - [Safety issues of traditional Chinese medical preparations containing arsenic substances: review starting from Niuhuang Jiedu Pian (Wan)]. AB - By comprehensively reviewing the origin and history of Niuhuang Jiedu Wan and its "derivatives", we studied the clinical records of realgar, investigated its clinical usage, dosage, efficacy, and toxicity in the literatures. We pinpointed the factors that might be associated with safety problems of Niuhuang Jiedu Pian (Wan) and other traditional Chinese medicine (TCM) preparations containing arsenic substances. In this article we also put forward suggestions for strengthening the surveillance and administration of similar TCM preparations. PMID- 17348200 TI - [Constrcution and application of Xinjiang fine-fleece sheep 2 times genome BAC library PCR screening system]. AB - In this study, we used our special regional fostering breed Xinjiang fine-fleece sheep's genome to construct its genome library. The average size of insert fragments of the library was 133 kb. At the same time 92.5% clones' insert fragments of the library were larger than 100 kb and some larger than 300 kb. If we supposed sheep's genome contenting 3 x 10(6) kilo-base, on the basis of the average insert fragment was 133 kb the library covered 8 times genome of Xinjiang fine-fleece sheep. The probability of the tagged fragment being screened from the library was 98.208%. To prove the BAC library had been the better rate of coverage,four molecular markers: DMB_EX2, MCMA36, CP73 and BM1258 located to MHC gene of chromosome 20 near region in xinjiang fine-fleece sheep had been screened positive clones from the constructed 2 times genome library PCR screening system and the average positive clones was 1.5. The screening result showed that the constructed genome library was fairly closed to the 8 times genome coverage and had no erroneous tendency, which made the library being of the utmost useful resource for studying functional gene, position cloning and improving the genome physical map of sheep. PMID- 17348201 TI - [Src kinase-MAPK signal pathway plays a role in proliferation of endothelial cells induced by o-HA]. AB - To investigate the effect of hyaluronan oligosaccharides (o-HA) on endothelial cell (EC) proliferation and the possible mechanism involved. The cell proliferation was determined by cell counting and flow cytometer, and the phosphorylation of Src kinase and ERK-1/2 as well as the expression of cyclin D1 were assayed by western blot. o-HA at concentration of 10 microg/ml caused a significantly increase in both cell cycle and cell number of EC. With increasing time and amount of o-HA of exposure, there was no further increase in the growth of cells. The cell proliferation started to be significant at 12 hr and reached peak at 72 hr. At the same time,the phosphorylation of Src kinase and ERK-1/2 was enhanced after treated with l microg/ml of o-HA at 5 min and the expression of cyclin D1 was enhanced by treating PIEC cells with o-HA at 3 hr. o-HA may increase EC growth by stimulating the Src kinase and MAPK signal pathway and thus promote the proliferation of PIEC cells,in which the regulation of cyclin D1 expression may be involved. PMID- 17348202 TI - Preliminary identification of Citrus changshanhuyou elite genotypes by molecular markers. AB - Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) analyses were used in elite genotypes identification of Citrus changshan-huyou and analysis of its origin. 12 out of 100 RAPD primers and 11 out of 105 ISSR primers could generate reproducible polymorphic fragments. The RAPD-PCR and ISSR PCR assays revealed that 64 bands out of 117 (the percentage of polymorphic bands, PPB=54.7%) and 58 bands out of 94 (PPB = 61.7%) were polymorphic, respectively. ISSR and RAPD produced 15 and 12 genotype-specific and species specific molecular markers. Analysis of molecular variance (AMOVA) was used to calculate the similarity values according to these polymorphic bands, and a dendrogram was constructed using NTSYS-pc software. Each genotype and species in this study could be distinguished from others, suggesting that DNA profiles based on ISSR and RAPD markers have produced potential diagnostic fingerprints for various species, and also for genotypes. The molecular phylogenetic tree shows that C. changshan-huyou and C. sinensis formed a subcluster, so we can conclude that C. sinensis is an assured parent of C. changshan-huyou. However the largest genetic distance was found between C. grandis and C. changshan-huyou, it might be explained that C. changshan-huyou is the origin of multitude of natural hybrids from C. sinensis, C. grandis and other species of Citrus. PMID- 17348203 TI - [Antibody-induced ozone production and its potential effects on pathogenesis of atherosclerosis]. AB - In the present study, we measured the antibody-catalyzed 03 formation from THP-1 monocytes activated by phorbol myristate acetate (PMA) by indigo carmine bleaching reaction test, and the accumulation of cholesterol in THP-1 monocytes by fluorescence spectrophotometric method, and analyzed the cholesterol ozonation product 5,6-secosterol by high-performance liquid chromatography (HPLC), to explore the potential effect of antibody-catalyzed water oxidation on pathogenesis of atherosclerosis. It was showed that THP-1 monocytes incubated with human IgG and PMA evidently produced an oxidant with the chemical signature of 03 which could bleach indigo carmine, and be intensified or inhibited respectively by catalase and vinylbenzoic acid. In the THP-1 monocytes incubated with human IgG, PMA and LDL, the intracellular accumulated total cholesterol (TC), free cholesterol (FC), cholesteryl ester (CE) and the CE/TC increased evidently, and the cholesterol ozonation product 5,6-secosterol was also produced markly, all of that were inhibited by vinylbenzoic acid. These results demonstrated that the activated THP-1 monocytes possess the ability to produce O3 through antibody-catalyzed water-oxidation pathway, which could be a new mechanism concerned with atheriosclerosis. PMID- 17348204 TI - [Calcium distribution in the developing anther of Lycium barbarurn L]. AB - We used potassium antimonate to precipitate "exchangeable cellular Ca2+"-calcium that is sufficiently loosely bound to combine with antimonite, to investigate the feature of calcium distribution during anther development of Lycium barbarurn L. Before the stage of microspore mother cell, few calcium-induced precipitates were found in sporogenous cells and the somatic cells of anther wall. When microspore mother cell (MMC) preparing meiosis, calcium precipitates appeared in the cytoplasm of tapetal cells and callus wall surrounding MMC. After the meiosis of MMC,abundant calcium precipitates were accumulated in the cytoplasm of early microspores,and then in pollen wall, especially in the part of germ-pores. During the late microspore stage,a big vacuole formed and the nucleus was forced to move to peripheral region. Calcium precipitates decreased sharply and might dissolve in the large vacuole. After microspore mitosis, calcium precipitates appeared in the big vacuole of 2-cellular pollen,and then the vacuole disappeared. After that, the calcium precipitates again appeared in the cytoplasm of 2-cellular pollen, and the cytoplasm became densely and storage materials like starches accumulated inside the pollen grains. When pollen maturating,many small calcium precipitates distributed in its cytoplasm,especially in nucleus. The feature of calcium distribution in the anther of Lycium barbarurn L. means that it plays some biological roles during microspore development. PMID- 17348205 TI - [Influence of white spot syndrome virus envelope protein Vp28 expressed in silkworm (Bombyx mori) pupae on immune response in Procambarus clarkii]. AB - Silkworm (Bombyx mori) pupae infected with recombinant baculovirus HyNPV-Vp28 were made vaccine,which was mixed with feed at a ratio of 2% (w/w). Procambarus clarkii were orally administered. The results of immune analysis showed that the phagocytic percent and phagocytic index of hemocytes increased significantly when compared the rVp28 treatment with control treatments (P < 0.05). Compared with control groups,the antibiotic activity, bacteriolytic activity and activities of phenoloxidase, superoxide peroxidation in serum in the rVp28 group were greatly increased (P < 0.05). The activities of acid phosphatase and alkaline phosphatase in serum and hepatopancrease tissues in rVp28 treatment were significantly higher than control treatments (P < 0.05). Vaccination with rVp28 showed that the cumulative survival,compared with control treatments, was significantly higher (P < 0.05). An oral challenge on the 35th day post-vaccination was followed,PRP values were then 64.29% and 58.33%, respectively. The epidermal cells of stomach, midgut, hepatopancreas, gill and epithelial tissue of moribund crayfishes were histologically characterized by hypertrophied nuclei and highly stained cells, but there was normal structure in the survivors-vaccinated after WSSV challenge. WSSV DNA was detected by PCR and Dot-blot with DIG-labeled DNA probe. The positive results were observed in stomach, hepatopancreas and gut of the moribund crayfishes and survivors in control groups, while negative reaction was observed in the tissues of survivors in rVp28 group. Vp28 expressed in silkworm (Bombyx mori) pupae played a role in improving the immune function of crayfish. PMID- 17348206 TI - [DNA fingerprinting analysis of silkworm embryo cell lines]. AB - DNA extraction and the polymerase chain reaction (PCR) were used on DNA genomes study of cell lines of Bombyx mori. DNA polymorphic marker analysis was conducted and DNA fingerprint of cell lines of Bombyx mori. was carried out using ISSR and RAPD. Primers that can reliably find polymorphic bands were screened out. 26 ISSR primers were selected from them any available, and 797 polymorphic bands were abtained through PCR amplification in 9 samples, including 3 embryo cell lines of Bombyx mori (BmE-SWU1, BmE-SWU2, BmE-SWU3), 5 passage cell lines (BmE, BmN, Sf9, Sf21, Hi5) and the embryos from which BmE-SWU1 originated. The ration of polymorphic bands was 89.9%. 43 RAPD primers were selected out through PCR amplification, and 1205 polymorphic bands were obtained in 9 samples. The ration of polymorphic bands was 76.6%. There were many DNA polymorphic bands differences in the cell lines of Bombyx mori. The special DNA markers of the 3 embryo cell lines were found respectively. The similarity index Nei and genetic distance of the 9 samples were calculated and the phylogeny tree of 9 samples was constructed by UPGMA. Results showed that 2 groups were divided,one group including the 3 embryo cell lines and the embryo of XQ has close relative. Another group constructed by five insect cell lines came from different species, their genetic distance was closer than the 3 embryo cell lines. PMID- 17348207 TI - [Study on the correlationship between the expression of nm23H1mRNA, TGF-beta1mRNA and tumor metastases, survival rate with prostate cancer]. AB - All the specimens were marked by CD31 antibody, the expression of nm23HlmRNA, TGF beta1mRNA was detected in 42 cases of prostate cancer in situ hybridization with EnVision and Leica-Qwin computer image analysis system. The Weidner's highest vessel density counting method was used to analysis the microvessel density(MVD) of the specimens,and the patients' viability rate after operation was investigated. The correlation between the expression of nm23H1mRNA, TGF betamRNA,CD31 and neoangiogenesis, hyperplasia of microvessel, tumor metastases in prostate cancer was studied. The positive expression of nm23H1mRNA in prostate cancer was 66.67% (28 cases). There was negative correlation between the positive expression of nm23H1mRNA and bone metastasizing, TNM staging,MVD in prostate cancer (P < 0.05). The positive expression of TGF-beta1mRNA was 78.75% (33 cases), and was positive correlative to the bone metastasis, TNM stages, MVD in prostate cancer (P < 0.05). It is significantly different (P < 0.01 or P < 0.05) with that in adjacent nontumorous tissue. The MVD (78.51 +/- 10.29/mm2) in prostate cancer was significantly (P < 0.05) higher than that in adjacent nontumorous tissue (34.19 +/- 9.27/mm2). The MVD (92.41 +/- 15.42/mm2) in those who died in five years (18 cases) was significantly higher (P < 0.05) than that (62.79 +/- 13.58/mm2) in those who were still alive. In tumor pathology grading,different differentiation, the difference of nm23H1mRNA positive expression was statistically significant (P < 0.05). Higher the nm23H1mRNA expressed,lower the bone metastasized,and higher the viability rate was. Therefore, the nm23H1 gene was thought to have the effect of suppressing prostate cancer occurring and bone metastasizing. Higher the TGF-beta1mRNA expressed, higher the tumor bone metastasized, and lower the viability rate was. Therefore, the TGF-beta1 gene was thought to have the promote genesis and metastasize of prostate cancer. There is close correlation between the CD31 expression, MVD and prostate cancer bone metastasizing. The higher MVD level indicated neoangiogenesis in prostate cancer. TGF-beta1mRNA promote neoangiogenesis induced by tumor and play an important role in bone metastasizing. PMID- 17348208 TI - [Identification of genes regulating alveolar morphogenesis by supression subtractive hybridization]. AB - Alveoli are the key functional units of the lungs where gas exchange takes place, yet little is known about the mechanisms of their formation. To identify the genes that regulate alveolar morphogenesis, we used suppression subtractive hybridization to isolate genes that differentially expressed during the formation of saccules and the remodeling of saccules into alveoli in the mouse. After differential screening, we got 118 candidate genes from two libraries. These genes associate with many aspects of life including proliferation, differentiation, regulation and so on. For example: Transient receptor protein 4(TRPC4) may associate with formation or remodeling of pulmonary vessels by increasing permeability of endothelia cells. Lectin, (galactose bindingl, Lgalsl) may play a significant role in stimulating smooth muscle growth in developing alveolar wall vessels and the development of pulmonary capillaries. Interesting, a putative neuronalprotein, P311 was found highly expressed in both the first and the secondary septation stages. Taking together SSH is a powerful method to identify differential expressing genes. PMID- 17348209 TI - [Ultrastructural observation of banana shoot-tip cell during cryopreservation by vitrification]. AB - Excised shoot-tips produced from banana plants belonging to cv. Guangdong No.1 (ABB group) were cryopreserved successfully by vitrification using the PVS2 solution. Ultrastructural of banana shoot-tips cells was also observed by using electron micryoscopy (TEM). The results showed that the plasmolysis became more and more severe during the course of dehydration. Cells were mainly damaged during the freezing and thawing process. Most cell protoplasts condensed, and cell organelles, cell membranes and nucleus envelopes were lethally injured after cryopreservation. But only a few cells located in the meristematic dome arose reversible process although their structures were varied. They could survive and regenerate plantlets after freezing conservation. PMID- 17348210 TI - [Study on the hepatoxicity mechanisms of Huangyaozi (Rhizoma dioscoreae bulbiferae) on mouse liver by cDNA microarray]. AB - cDNA microarray technique was used to study the mechanisms of liver injury caused by Huangyaozi at level of gene expression based on the biological functions of those differentially expressed genes. For the mice taking Huangyaozi for 15 days,there were 83 differentially expressed genes,among them 18 genes were up regulated and 65 genes were downregulated, and the increase of serum ALT,AST and tissue total protein were notable. For the mice taking Huangyaozi for 30 days, there were 1658 differentially expressed genes,among them 917 genes were up regulated and 741 genes were down-regulated. And the liver index, serum ALT and tissue total protein were all increased significantly but AST,AKP decreased significantly. There were 45 common differentially expressed genes in the two groups,among them 9 genes were upregulated,while the other 36 genes were down regulated. According to the differentially expressed genes with different duration for taking Huangyaozi, the phased change about occurrence and development of liver injury was analyzed. The results indicated that the gene expression profile of mouse liver cell could be changed significantly by taking Huangyaozi, which might be important for elucidating the mechanisms of liver injury caused by Huangyaozi. PMID- 17348211 TI - [Impact of reproductive hormone on mouse embryo sexes]. AB - The effects of reproductive hormone on mouse embryo sexes were studied with in vitro fertilization (IVF), in vitro culture (IVC) and sex identification. Results showed that it had no adverse effects on embryos cleavage and development after the embryos were incubated with the fertilization media with 17beta-E2, FSH and progesterone respectively at the concentration of this study. Mice embryos sex ratios significantly deviated from 1:1(P < 0.01) and skewed in favor of males at the concentration of 17beta-E2 attained 70 pg/mL and progesterone attained 99 pg/mL in IVF culture media respectively. 0.01-0.04 IU/mL FSH had no effects on the mouse embryo sexes. PMID- 17348212 TI - The history and clinical application of a chairside CAD/CAM dental restoration system. AB - Since its introduction by Sirona Dental Systems (Charlotte, North Carolina, USA and Bensheim, Germany) in 1985, the CEREC Chairside CAD/CAM restoration system has steadily earned a loyal following among dentists. This article describes the history and evolution of the CEREC System, its clinical application and treatment modality, the restorative materials used to fabricate the restorations and an overview of clinical findings regarding the in vivo performance of the materials. PMID- 17348213 TI - [The relationship of IL-1beta expressed in buccal cells and the polymorphisms of IL-1beta (+3953) with chronic periodontitis]. AB - PURPOSE: The purpose of this study was to investigate the relationship of IL 1beta expressed in buccal cells and the polymorphisms of IL-1beta(+3953) with chronic periodontitis. METHODS: Thirty-six patients with different severity of periodontal disease and thirty-six subjects with healthy periodontal tissues participated in this study. Buccal cells and peripheral venous blood samples were collected and the periodontal status were recorded. Immunohistochemical analysis of IL-1beta expressed in buccal cells was carried out and the polymorphisms in IL 1beta(+3953) were analyzed by polymerase chain reaction-restriction fragment length polymorphism after extracting DNA from peripheral venous blood. Then the differences in the level of IL-1beta expressed in buccal cells and the distribution of each genotype in IL-1beta(+3953) were compared. Multiple linear regression was used to correlate the periodontal status with the polymorphisms in IL-1beta(+3953) and the expression of IL-1beta) in buccal cells. RESULTS: The carrying ratio of IL-1beta(+3953) allel II in severe chronic periodontitis (12%) was significantly higher than the healthy control group(0). The level of IL-1beta expressed in buccal cells of patients with chronic periodontitis was also significantly higher than that of subjects with healthy periodontal conditions (chi2 = 365.095, P < 0.001). Clinical attachment loss and probing depth correlated positively with the expression of IL-1beta (CAL, P < 0.05; PD, P < 0.01) and no correlation was found between plaque index, bleeding on probing,the polymorphisms in IL-1beta(+3959) and the levels of IL-1beta. CONCLUSIONS: The results of this small sample study suggested that the level of IL-1beta expressed in buccal cells showed the severity of chronic periodontitis and the IL 1beta(+3953) genotype did not make the level of IL-1beta expressed in buccal cells changed significantly. PMID- 17348214 TI - [Expression and significance of hTERT, c-fos and c-jun in ameloblastoma]. AB - PURPOSE: To investigate the expression of c-fos, c-jun and hTERT mRNA in human ameloblastoma (AB) and to determine their clinicobiological significance. METHODS: In situ hybridization was performed to examine the expression of c-fos, c-jun and hTERT mRNA in AB and 7 cases of normal oral mucosa (NOM), 16 cases of keratocystic odontogenic tumor (KCOT) were selected as controls. SPSS10.0 software package was used to perform chi2 test, Fisher's exact probability and Kendall correlation analysis. RESULTS: There was no expression of c-fos and c-jun mRNA in NOM, while hTERT mRNA expressed positively only in 1/7 cases of NOM. c fos, c-jun and hTERT mRNA expressed positively in KCOT and AB with different degrees. No significant difference at c-jun mRNA levels between KCOT or AB and NOM was found. Kendall correlation analysis showed positive correlation between c fos and hTERT mRNA (r(k) = 0.024, P < 0.05). CONCLUSION: c-fos gene plays an important role in the occurrence, development and proliferation of AB, possibly through acting as a cardinal subunit of AP-1 to participate the regulation of the telomerase activity. PMID- 17348215 TI - [A preliminary study on the relationship between the wearing time of full denture and EMG in edentulous patients]. AB - PURPOSE: This study was aimed to analyze the relationship between the periods of wearing time of full denture and function of mastication in edentulous patients. METHODS: Electromyogram (EMG) was done at an initial time of wearing full denture for 30 patients (Group A) and at an interval of wearing full denture for more than 3 months for 32 patients (Group B). EMG activities were recorded for 2 pairs of muscles (anterior temporalis, masseter) by means of Medelec Synergy Electromyography. Student's t test was used for statistical analysis. RESULTS: EMG amplitude of Group A was significantly lower than that of Group B (left anterior temporalis P < 0.05, bilateral masseter P < 0.05). Group A has larger area than Group B (P < 0.05); No significant difference was found in asymmetry index between Group A and Group B (P > 0.05). CONCLUSION: The function of mastication in patients who wore full denture for short time has not been achieved as expected. PMID- 17348216 TI - [Study of facial soft tissue profile on angle Class II malocclusion with various vertical growth patterns]. AB - PURPOSE: To investigate the difference of the facial soft tissue profile on Angle Class II malocclusion with various vertical growth pattern. METHODS: The samples (n = 84) were divided into three groups (low-angle, medial-angle, high-angle group) based on their SN-MP angle. Their cephalograms were measured and all data were analyzed by SPSS12.0 software. RESULTS: There were some regular changes in most facial profile variables while the mandibular plane angle increased: the facial profile convexity and the upper- and lower-lip convexity increased significantly; the depth of anterior lower face decreased from too large to small; the radian of upper- and lower- lip curve changed from too winding to upright. CONCLUSION: Vertical growth patterns make significant differences to soft tissue facial profile on Angle Class II malocclusion. PMID- 17348217 TI - [Evaluation of peri-implant augmentation with collected bone]. AB - PURPOSE: To determine the amount of bone harvested from dental implant osteotomies with aspeo 12000 bone collector, to characterize the nature of the debris, and to evaluate the histological viability and clinical effect of peri implant augmentation with immediate implantation of collected bone. METHODS: From May 2004 to Oct 2005, 15 recruited patients without peri-implant imperfections underwent 18 ITI implants installation. During the implant bed preparation, 18 samples of bone were collected using the instrument and an analysis of variance was used to determine if there were statistical differences between female versus male, maxilla versus mandible, anterior versus posterior alveolar bone. After decalcification, the material from each sample was fixed in paraffin wax and stained with haematoxylin and eosin, all sections were examined by optical microscope and the proportion of bone was established histomorphometrically. During the time, 12 defects occurred in 11 patients when 16 dental implants were installed, and all the defects were augmented with collected bone debris simultaneously. RESULTS: About 93% volume of 'wet' bone could be obtained from one dental implant osteotomy, and there were no statistical differences between female and male, maxilla and mandible, anterior and posterior alveolar bone. Histological observation showed that all samples contained bone and coagulum, the mean bone proportion was 94.2%. 3 to 6 months after surgery, the defects were successfully augmented, and during the secondary operation, bone growth was found over the defects. CONCLUSION: The use of bone collectors is a good method for obtaining material to fill small bone imperfections in dental implantation. PMID- 17348218 TI - [Analysis of periodontal status in pregnant women with a diagnosis of threatened premature labor]. AB - PURPOSE: To evaluate the associations between periodontal conditions and delivery outcomes in pregnant women with a diagnosis of threatened premature labor (TPL). METHODS: Eighty systemically healthy pregnant women were enrolled in the study. The case group was composed of 40 pregnant women hospitalized with the diagnosis of TPL and the control group was composed of 40 normal pregnant women. Periodontal examinations included assessments of plaque index (PLI), clinical attachment loss (CAL), probing depth (PD), bleeding index (BI) and the percentage of periodontitis sites (PD > 3 mm, CAL > or = 2mm). The serum level of IL-6 was determined using commercially available enzyme-linked immunoassays (ELISA). The data were analyzed with SPSS11.0 software package for chi2 test, Student's t test and Pearson correlation analysis. RESULTS: 40 subjects were clarified as TPL and 14 as TPL-PB. 26 TPL women subsequently delivered TB infants. No infants were delivered as PB in 40 subjects clarified as non-TPL. There were no significant differences in the mean ages and gestational age at examination between the non TPL and TPL groups or between the TPL-TB, and TPL-PB groups. There were significant differences in gestational age at delivery and birth weight between the non-TPL and TPL groups or between the TPL-TB, and TPL-PB groups (P < 0.05). The mean PLI, percentage of periodontitis sites and IL-6 levels were significantly higher in the TPL group than those of the non-TPL group. The mean PLI, BI, and percentage of periodontitis sites were significantly higher in the TPL-PB group than those of the TPL-TB group. Significant negative correlations were observed between the gestational age at delivery and percentage of periodontitis sites as well as BI (P < 0.05). CONCLUSION: Periodontal inflammation might be involved in the pathogenesis of preterm birth. PMID- 17348219 TI - [Detection of masticatory muscle in bilateral distal-extension partially edentulous patients before and after prosthetic rehabilitation by surface electromyography]. AB - PURPOSE: To analyze the difference of masticatory muscle in bilateral distal extension partially edentulous patients before and after prosthetic rehabilitation by surface electromyography. METHODS: Twenty-seven bilateral distal-extension partially edentulous patients were randomly selected, and be detected before and after prosthetic rehabilitation by surface electromyography. During the detection, the amplitudes of the anterior temporalis and masseter muscle were registered. Using them, the asymmetry index of total, asymmetry index of the masseter, asymmetry index of the anterior temporalis and mastication index were calculated. Student's t test was used to analyze the results. RESULTS: The asymmetry index of total and asymmetry index of the masseter in group of one month after prosthetic rehabilitation increased significantly than that in the group before prosthetic rehabilitation (P < 0.05); The asymmetry index of total and asymmetry index of the anterior temporalis in group of three or six months after prosthetic rehabilitation decreased significantly than that in the group before prosthetic rehabilitation (P < 0.05); The mastication index decreased gradually after prosthetic rehabilitation, the difference was also be significant between group of three or six months after prosthetic rehabilitation and group before prosthetic rehabilitation (P < 0.05). CONCLUSIONS: After prosthetic rehabilitation, the equation and reservation of muscle's energy in bilateral distal-extension partially edentulous patients were significantly better than before. Whereas it costed more than three months for patients to adapt the dentures. PMID- 17348220 TI - [Masticatory efficiency and phonetics effects of double dentition denture for cleft lip and palate patients with different base design]. AB - PURPOSE: To evaluate the masticatory efficiency and phonetics in patients with cleft lip and palate before and after double dentition denture treatment, and determine the results of the treatment. METHODS: 6 patients who had cleft lip and palate with defect smaller than 1 cm x 1 cm or submucous cleft palate were selected to undergo double dentition denture treatment. Two kinds of base design were used. One was with artificial teeth and buccal base only. The other was with artificial teeth and base on both the buccal and palatal sides. Masticatory efficiency and phonetics effect were tested before and immediately after treatment and 1 month after treatment. The data were analyzed using SPSS11.0 software package for paired t test. RESULTS: There was statistically significant difference in masticatory efficiency, before and immediately after treatment and 1 month after treatment (P < 0.01). As for phonetics , there was statistically significant difference on F2 and F3 before and immediately after treatment as well as 1 month after treatment (P < 0.05). While there were no statistically significant difference both on masticatory efficiency and phonetics between the two kinds of design. CONCLUSION: Both the two kinds of treatment can improve the masticatory efficiency and phonetics effectively. It is not necessary to use the palatal base when the defect is smaller than 1 cm x 1 cm or submucous cleft palate present. PMID- 17348221 TI - [Long-term observation of 920 porcelain fused to metal prostheses]. AB - PURPOSE: To evaluate the long-term clinical results of porcelain fused to metal prostheses. METHODS: Since January 1995, 920 porcelain fused to metal prostheses were fabricated. The long-term outcome were evaluated according to the condition of the prosthese, abutment and the periodontal tissue in the respects of successful rate and causes of failure. RESULTS: 74 patients were found to be during the follow up period, including 36 anterior crowns (46 units), 18 posterior crowns (22 units), 12 percentage of anterior bridges and 8 posterior bridges. The overall failure rate was 8.04%, 4.84% for crown, 8.77% for bridge. The failed prostheses was 5.39%. CONCLUSIONS: Porcelain fused to metal prostheses is an ideal method for restoration. The standard process both for the clinician and the technician must be obeyed to improve the success rate. PMID- 17348222 TI - [Cost effectiveness analysis of two methods of preparing molar root canals]. AB - PURPOSE: To evaluate the short-term clinical curative effects, cost effective ratio between ProFile nickel-titanium rotary preparation technique and stainless steel hand K-files preparation technique in molar root canal therapy. METHODS: All patients were randomly divided into two groups: 49 cases were prepared with stainless steel hand K-files in routine preparation technique; 45 cases were prepared with ProFile nickel-titanium rotary instruments in step-down technique. The clinical symptoms and cost were recorded. The data was analyzed by SPSS11.5 software package. RESULTS: The satisfactory rate of clinical effect of the NRPT group was significantly higher than SSPT(P = 0.034); The mean cost of the NRPT was significantly higher than SSPT (P = 0.001), the satisfactory rate of NRPT in severe curve subgroup was significantly higher than that of SSPT (P = 0.007), however, the C/E of NRPT was 394.52 Yuan less than SSPT. The former was 192.04 Yuan more than the latter in light curve subgroup. When it was classified by periapical condition before treatment, the satisfactory rate of NRPT was significantly higher than SSPT in negative subgroup yet (P = 0.012), the C/E of the former was 32.32 Yuan more than the latter; nevertheless, the C/E of the former was 376.47 Yuan more than the latter in positive subgroup; CONCLUSIONS: It is better to prepare with ProFile nickel-titanium rotary preparation technique in severe curve subgroup, however, the light curve subgroup should be prepared with stainless steel hand K-files preparation technique. To patients with positive periodontopathy, SSPT would save the cost of treatments, nevertheless, NRPT group have a higher short-term recent effect. PMID- 17348223 TI - [Application of low intensity ultrasound in the extraction of totally impacted mandibular third molars]. AB - PURPOSE: To observe the clinical effects of low intensity ultrasound in extraction of totally impacted third molars. METHODS: 40 patients with totally impacted third molars on both sides of the mandible verified by X-ray were selected. After extraction of the teeth, the socket on one side was treated with low intensity ultrasound while the other side underwent no treatment. Statistical analysis was performed with SPSS 10.0 on all patients in form of pain, swelling, dry socket and bone healing. RESULTS: In the experimental group, 4 patients complained of severe pain while 16 patients in the control group (P < 0.05). Moderate or severe swelling were not uncommon in both experimental and control groups (P > 0.05); No patients suffered from dry socket in the experimental group and 4 patients suffered from dry socket in the control group (P < 0.05); There were 35 patients with complete bone healing in the experimental group while 21 patients with complete bone healing in the control group (P < 0.01). CONCLUSIONS: The use of low intensity ultrasound in extraction of totally impacted mandibular third molars reduced the severity of post-operative pain and the incidence dry socket, and it also stimulated bone healing, but it showed no effect on relieving post-operative swelling. PMID- 17348224 TI - [Evaluations of self-perceived orthodontic treatment need using 2 different scales in adolescents]. AB - PURPOSE: To evaluate the self-perceived dental aesthetics through visualized analogue scale (VAS) and aesthetic component (AC) of index of orthodontic treatment (IOTN) among adolescents in Shanghai area. METHODS: The investigation was carried out among 302 students (148 boys and 144 girls) aged 11-13 years. Self-perception of the dental aesthetic appearance was evaluated through VAS and AC. Additionally, the objective dental aesthetics were scored by orthodontists using AC and the actual dental attractiveness satisfaction was determined by a simple question. The data was analyzed using SPSS11.0 software package for Spearman correlation analysis. RESULTS: Generally, no statistically significant sex differences were found in relation to the VAS score and SAC degree (P > 0.05). No correlation was found between actual dental attractiveness satisfaction and self-perceived AC grade (r = 0.04. P = 0.441). However, statistically significant, positive, strong correlations were found between the actual dental attractiveness satisfaction and VAS score (r = 0.80, P = 0.000). And meaningful relation between the AC and VAS score was found. CONCLUSIONS: VAS showed high ability to predict the self-perceived dental aesthetics and act as a simple and useful tool, which can be used in further investigations. PMID- 17348225 TI - [A three-year clinical evaluation of ceramic optimized polymer posterior inlays]. AB - PURPOSE: To evaluate the clinical results of ceramic optimized polymer (Targis) posterior inlays. METHODS: 345 type I cavities were divided into two groups: 170 in Targis inlays group (42 premolars and 128 molars) and 175 in control group (composite resin inlays, 45 premolars and 130 molars). The clinical effects of Targis inlays and composite resin inlays in posterior teeth were compared in marginal discoloration, marginal adaption, secondary caries, anatomic shape integrity, fractures of tooth and color match 3 years later. The data were analyzed using Chi-square test. RESULTS: 3 years after treatment, 166 Targis inlays were followed up, 2 had marginal discoloration, 158 had good marginal adaption, 162 had anatomic shape integrity, 1 had secondary caries, 161 had color match, and 5 had fractures of teeth. 169 composite resin inlays were followed up, 27 had marginal discoloration, 134 had good marginal adaption, 150 had anatomic shape integrity, 20 had secondary caries, 164 had color match,5 had fractures of teeth. The marginal discoloration, marginal adaption, secondary caries, anatomic shape integrity of Targis inlays were better than that of composite resin inlays (P < 0.05), but fractures of teeth was not different between inlays in the two group (P > 0.05). CONCLUSION: Targis posterior inlays is a good newly developed prosthesis. PMID- 17348226 TI - [A study on the mechanism of inducing apoptosis of Tca8113 cells by means of ultrasound hyperthermia]. AB - PURPOSE: To investigate the mechanism of apoptosis in Tca8113 cells induced by ultrasound hyperthermia by detecting changes in related index. METHODS: Tca8113 cells were treated in vitro by ultrasound hyperthermia in different heating temperatures (38 degrees C to 44 degrees C,10 minutes) and heating times (42 degrees C,10 to 60 minutes), and then the dynamic changes of early apoptosis and secondary necrosis treated by 42 degrees C for 10 minutes were assayed to detect deltapsim and Caspase-3 levels of different groups by flow cytometry (FCM). The means of each group were compared by ANOVA with SAS6.12 software package. RESULTS: After heated by ultrasound in 42 degrees C for 10 minutes, the early apoptosis of Tca8113 was detected. The apoptosis index reached its highest level at the 6th to 8th hour, then decreased rapidly and maintained in a lower level after 12 hours. The level of secondary necrosis increased with the level of early apoptosis, but kept in a higher level until the 10th hour, the level of secondary necrosis correlated with that of the early apoptosis (r = 0.7909, P = 0.0064). The fraction of cells with low mitochondria membrane potential and increased activity of Caspase-3 were detected either in the heating-temperature grads group or in the heating-time grads group, which showed significant relationship between thetwo apoptosis related index (r = 0.89189, P = 0.0029 in the heating temperature grads group; r = 0.9679, P = 0.0003 in the heating-time grads group). CONCLUSIONS: Tca8113 cells developed apoptosis after heated by ultrasound hyperthermia along with deltapsim level decreasing and Caspase-3 activity increasing. Ultrasound hyperthermia induces apoptosis of Tca8113 cells by the mitochondrum-Caspase pathway. PMID- 17348228 TI - [The accuracy of 3D-CT volume rendering for craniofacial linear measurements]. AB - PURPOSE: This study was designed to determine the consistency of craniofacial measurements using spiral computed tomography volume rendering by computer systems and sliding caliper. METHODS: The study population consisted of 12 cadaver heads which were examined with spiral CT. The archived CT data were transferred to a workstation, and 3D-CT volume rendered images were generated using computer graphics tools. Linear measurements (n = 20), based upon conventional craniometric anatomical landmarks (n = 16) were made, by Display Tools and sliding caliper respectively. The consistency between the two measurements was analyzed by paired t test using SAS9.0 software package. RESULTS: The results demonstrated no statistically significant difference between imaging measurement and physical measurement, P > 0.05. CONCLUSIONS: There is significant consistency between spiral CT measurement and physical measurement for craniofacial linear distance. 3D-CT volume rendering images using craniometric measurements can be used for clinical and basic studies in stomatology. PMID- 17348227 TI - [Difficulty assessment of root canal therapy in Chinese permanent maxillary anterior teeth]. AB - PURPOSE: To assess the difficulty of root canal therapy in Chinese permanent maxillary anterior teeth by radiographic methods in vitro. METHODS: 80 maxillary anterior teeth including 27 maxillary central incisors, 22 maxillary lateral incisors and 31 maxillary canines were collected and X-rayed in 3 individual directions: labiopalatal projection, mesiodistal projection and the maximal angle shot. Three anatomic risk factors: root curvature, calcification and working length of root canal therapy were assessed by difficulty assessment standards and criterions. Kruskal-Wallis test was used to analyze the data. RESULTS: The results showed that the root canal therapy of 2 and 3 were significantly more difficult than 1, P < 0.05; while there was no significant difference between 2 and 3, P > 0.05. In 1, the results of difficulty assessment of root canal therapy were significantly different among 3 individual X-rays which were projected from 3 different directions (P < 0.05). The difficulty caused by root curvature was significantly greater than calcification and working length in labiopalatal X-ray in 1 (P < 0.05) and 2 (P < 0.01), while there was no significant difference among these 3 risk factors in 3 in labiopalatal projection (P > 0.05). CONCLUSIONS: The results suggest that the labiopalatal X-rays can be safely regarded as the reliable projection shot for difficulty assessment before endodontic procedures. Root curvature was by far the most important risk factor that affected the difficulty of root canal therapy in 1 and 2 while root curvature, calcification and working length played the same roles in root canal therapy of 3. PMID- 17348229 TI - [Effects of rh-GH on the remodeling of periodontium in the ovariectomized rats after orthodontic tooth movement]. AB - PURPOSE: To investigate the effects of the recombinant human growth hormone (rh GH) on the periodontal cells in the ovariectomized rats after orthodontic tooth movement. METHODS: Thirty seven-week-old SPF female Wistar rats were randomly divided into three groups: the control group, the ovariectomy-saline group (OVX NS group) and the variectomy-GH group(OVX-GH group). Different treatments, including variectomy and injecting normal saline solution, were adminstrated on the rats of the three groups. The number of osteoclast in the compressed alveolar bone was counted on the fifteenth and thirtieth days. Histological changes were observed. The data was analyzed with ANOVA by SPSS12.0 software package. RESULTS: By ANOVA analysis, there were significant differences in the number of osteoclast between the three groups in the same period. The number of osteoclast in the compressed alveolar bone of OVX-NS group was significantly more than that of the OVX-GH group (P < 0.05), and that of the control group was the least. In the same group, there wasn't significant difference between the rats killed 15 days later and 30 days later (P > 0.05). The trauma and inflammation of periodontal membrane of OVX-GH group had been significantly improved compared with the OVX-NS group. CONCLUSION: It is suggested that injecting rh-GH can decrease the number of osteoclast in the compressed alveolar bone in the adult rats after orthodontic tooth movement. At the same time, it can improve the recovery of pathologic changes of periodontal tissue caused by the orthodontic force. There will be a synergetic effect between adult orthodontic treatment and rh-GH. PMID- 17348230 TI - [The expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in transplanted tumor of salivary adenoid cystic carcinoma cell lines]. AB - PURPOSE: To study the differential expression pattern of MMPs and TIMPs in ACC-M and ACC-2 tumor model. METHODS: High and low metastatic tumor models were set up by transplantion of ACC-M and ACC-2 to nude mouse respectively. Then 3 mice in each group were selected randomly to detect the mRNA level of MMP-2, MMP-7, MMP 9, TIMP-1 and TIMP-2 using semiquantitative RT-PCR,GAPDH was used as internal control. Meanwhile, the expression of MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 in each transplanted tumor were determined by immunohistochemical assay, and IOD value of immunohistochemical reaction was measured. All data were analyzed by SPSS11.5 software package for Student's t test. RESULTS: The results of RT-PCR and immunohistochemistry showed an up-regulation of MMP-2, MMP-7, MMP-9 and TIMP 1 in ACC-M tumor model compared with ACC-2 model (P < 0.05), while the expression of TIMP-2 showed no significant difference between the two models (P > 0.05). CONCLUSION: The differential expression pattern of MMP-2, MMP-7, MMP-9, and TIMP 1 in 2 tumor models may result in different metastasis potential; The 2 tumor models provide good study model for investigation of the metastatic mechanism of salivary adenoid cystic carcinoma. PMID- 17348231 TI - [Three-dimensional simulation of protrusive movement for complete denture on articulator]. AB - PURPOSE: This study was designed to investigate an algorithm model, which can simulate the protrusive movement for complete denture on articulator. METHODS: A typical edentulous case with one-year complete denture was selected for this study. A new complete denture remounted on articulator Hanau H2 was scanned and reconstructed by three-dimensional technique. With the geometrical parameters of the articulator, a series of mathematical equations describing the three dimensional protrusive movement of complete denture on articulator were solved by programming in Matlab6.5 (a language for technical computing). RESULTS: The algorithm model to simulate the protrusive movement of complete denture on articulator was established and was testified by the true case in this study. CONCLUSIONS: This study verified the use of a new method to quantitatively study the protrusive movement simulation of complete denture in terms of spatial coordinates. And the quantitative simulation may play an important role in further research of the dynamic occlusion to improve dental restorative procedures. PMID- 17348232 TI - [The reconstruction of geometric models of dentition defects based on 3 dimensional industrial computed tomography image]. AB - PURPOSE: A technique on data capture of plaster models for building 3-dimensional geometric models of dentition defects was presented for the purpose of further computer-aided design and manufacture (CAD/CAM)of removable partial denture. METHODS: A plaster model with dentition defects was scanned with low energy X-ray industrial computed tomography (ICT) for ICT image. The data after image processing and vectorization were transferred to a customized reverse engineering software system, and a CAD model of dentition defects was reconstructed. Then a 3 dimensional digital model of removable partial denture framework was created with CAD/CAM software system. Import/export of the data was in STL format. RESULTS: Dense and uniform data points without blind areas were acquired and the structure of the reconstructed CAD model of dentition defects was clean and smooth. CAD model of framework was then obtained. CONCLUSIONS: The method presented is practical for 3-dimensional data capture, and it helps build reliable 3 dimensional geometric models with better spatial resolution and higher precision than conventional technique with medical CT. PMID- 17348233 TI - [Study of the strength of Estenia hybrid ceramic material and the effect of reinforcement]. AB - PURPOSE: Estenia hybrid ceramic material (Kuraray Co., Osaka, Japan) is a new developed indirect resin composite with the advantages of both ceramic materials and resin composites. The purpose of this study was to evaluate the compressive strength of the crowns and the flexural strength of the three-unit fixed bridges which were made of Estenia hybrid ceramic material. METHODS: Crowns and three unit fixed bridges were fabricated with the Estenia hybrid ceramic material. The compressive strength of the crowns and the flexural strength of the three-unit fixed bridges were evaluated. The results was compared with that of other resin composites (Artglass,Solidex and Targis) tested previously in the same way. RESULTS: The load required to fracture the unreinforced Estenia crowns was 600.20N. The load required to fractured the unreinforced Estenia three-unit fixed bridges was 302.53N. CONCLUSION: The strength of Estenia material was better than other resin composites made of Artglass, Solidex and Targis. PMID- 17348234 TI - [Preparation and structural detection of antibacterial hydroxyapatite coating material on Ti implant]. AB - PURPOSE: To investigate the method for preparing antibacterial hydroxyapatite coating material on Ti implant,and detect its surface feature, chemical composition and the crystal structure. METHODS: The antibacterial hydroxyapatite coating material which contained silver-zirconium phosphate antimicrobial was prepared on the Ti implant by using vacuum plasma spraying technology. Samples were divided into 4 groups according to weight percent of the antimicrobial: group A (0), group B (2%), group C (5%) and group D (10%). The surface feature of each sample was observed under scanning electric microscope. The chemical composition and the crystal structure was detected by electronic probe and X-ray diffraction method respectively. RESULTS: The surface feature of each sample showed globular granule with caky structure and air pore. The crystal structure of group A, B, C mainly showed characteristic absorption band of Ca10(OH)2(PO4)6 which degraded while antimicrobial content increased. Except Ca10(OH)2(PO4)6 and CaZr (PO4)2, Na6CaP2O09 also appeared in group D. Ag+ could not be detected by electronic probe in group A and B. The contents of Ag+ in group C and D were similar. CONCLUSION: The antibacterial hydroxyapatite coating material which contained silver can be prepared on the Ti implant by using vacuum plasma spraying technology. The appropriate weight percent of the antimicrobial was 5%. PMID- 17348235 TI - [Effect of implantation and implant connection on craniofacial bone growth in Beagle dogs]. AB - PURPOSE: To study the effects of implantation and implant connection on Beagle craniofacial bone growth. METHODS: Eight Beagle dogs were randomly divided into two groups: unconnection group (4 dogs) and connection group (4 dogs). Two implant were implanted respectively in the lateral maxilla and zygomatic bone in each dog, the contra lateral side was used as normal control. Two implant was connected in the connection group 1 month later. Student's t test was used to analyze the data using SPSS11.5 software package. RESULTS: In the unconnection group, the distance increased between implants along with craniofacial bone growth; In the connection group, the distance fixed between implants along with craniofacial bone growth. The craniofacial values revealed no significant differences in the two groups (P > 0.05). CONCLUSION: The effect of implantation is localized and no inhibition in development of craniofacial bone is noted. PMID- 17348236 TI - [Comparison of two carving methods applied for triple-sized plaster tooth in dental anatomy teaching]. AB - PURPOSE: To explore how to apply polyhedron method and bisection method reasonably in teaching by comparing the two carving methods for triple-sized plaster tooth. METHODS: 43 students were randomly divided into two groups as follows: polyhedron method group (n = 22) and bisection method group (n = 21). A comparison was made between the two carving methods by taking right maxillary central incisor carving as a sample for the anterior tooth carving and taking right maxillary first molar carving as a sample for the posterior tooth carving. Paired test and grouped t test were used for data analysis; the results were assessed by SAS6.12 software package. RESULTS: For the beginners, regarding to right maxillary central incisor carving, there was no significant difference between the two methods (P > 0.05). But regarding to right maxillary first molar carving, the carving performance of polyhedron method group was significant better than bisection method group (P < 0.05). After 11 months, as for the two carvings mentioned above, students in the two groups both had made significant progresses compared with the beginners (P > 0.01). While regarding to right maxillary central incisor carving, progresses of the two groups were not significant (P > 0.05). But regarding to right maxillary first molar carving, the students in bisection method group had made greater progresses than students in polyhedron method group (P < 0.01). CONCLUSION: It's concluded that, in order to obtain better teaching effects, carving methods should be chosen appropriately in teaching according to different teeth and different study stages. PMID- 17348237 TI - [Clinical study on the treatment of recurrent aphthous ulcer with zhong tong'an combined with dexamethasone]. AB - 100 cases of recurrent aphthous ulcer (RAU) were randomly divided into two groups, 55 cases in the experimental group who were given traditional Chinese medicine Zhong tong'an capsules combined with dexamethasone tablets, while 45 cases in the control group who were given dexamethasone tablets alone. The course of treatment was 9 days, and follow up period was 6 months. The overall effective rates were 94.45% and 77.78% in the experimental group and the control group respectively. There was significant difference between the two groups in the treatment outcome (P < 0.05). PMID- 17348238 TI - [Primary intraosseous carcinoma of the jaws: case report and review of the literature]. AB - Because of lacking characteristic symptoms, primary intraosseous carcinoma of the jaws can't be easily diagnosed early. A case of intraosseous mucoepidermoid carcinoma of the maxilla was reported and relevant literature was reviewed. The possible etiology, clinical symptoms, radiology, histopathology, diagnosis and treatments were discussed. PMID- 17348239 TI - Prevalence of asthma and comorbid allergy symptoms in Singaporean preschoolers. AB - The cross-sectional prevalence of wheeze, rhinitis and eczema in 7,549 randomly selected Singaporean preschoolers aged 4 to 6 years old is reported in this study. Cumulative and past 12 months ('current') prevalence of wheeze was 27.5% and 16.0%, respectively. 'Asthma' was reported by 11.7%. Current rhinitis prevalence was 25.3% and rhinoconjunctivitis, 7.6%. Current chronic rash affected 13.5% of subjects while 9.9% reported chronic rash with flexural distribution. After multivariate analysis, the main risk factors for 'current wheeze' and self reported asthma, respectively, were family history of allergy (adjusted odds ratio [aOR] 3.22 [2.79-3.71], aOR 3.93 [3.34-4.63]); concurrent rhinoconjunctivitis (aOR 4.04 [3.31-4.92], aOR 3.02 [2.43-3.76]); concurrent chronic flexural rash (aOR 2.56 [2.13-3.08], aOR 2.95 [2.41-3.62]) and previous respiratory infection (aOR 4.80 [4.17-5.53], aOR 3.28 [2.80-3.85]). Thus, these allergy-associated symptoms already affect a considerable portion of children by the preschool years, supporting the need for allergy education and intervention program in this age group. PMID- 17348240 TI - Increasing asthma care knowledge and competence of public health nurses after a national asthma education program in Taiwan. AB - One of the responsibilities of a public health nurse is to provide asthma education to local residents. However, there have been no comprehensive education programs for public health nurses on asthma care in the past. This study aimed to determine level of competence of public health nurses on asthma care in order to improve their capability through a one-day national asthma education course. In addition to lectures on updated asthma management information, data was obtained through demonstrations and practice on inhalation techniques of various kinds of inhaled devices, including the ability to use and interpret the data of a peak flow meter. Two written examinations with the same questions were given to participants before and right after the lectures. All of the 560 public health nurses in the 392 public health bureaus were invited to join the program and 522 (93.2%) participated. Five hundred and six completed both the pre- and post tests. Before the national education program, only 10.9% of the participants knew the purpose of the peak flow meter, while 62.6% had never heard of it. Initially, they showed less confidence on teaching patients on the use of inhaled devices (2.36 and 2.59 in 5 scales). Comparing the two tests, there was a significant increase in the public nurses' knowledge as regards: 1) the general concept of asthma, 2) prevention of trigger factors and environmental control, 3) proper medication knowledge, 4) peak flow meter (PEF) monitoring, and 5) intervention after acute exacerbation of asthma (p < 0.001). A well-designed course on asthma management is an efficient scheme to improve public health nurses' knowledge and confidence on asthma care. PMID- 17348242 TI - Autologous serum skin test in chronic idiopathic urticaria: prevalence, correlation and clinical implications. AB - Some cases of chronic idiopathic urticaria (CIU) have histamine-releasing IgG autoantibodies in their blood. This disease subgroup is called "autoimmune urticaria". To date, the autologous serum skin test (ASST) is the best in vivo clinical test for the detection of basophil histamine-releasing activity in vitro. This study aimed to find the prevalence of ASST positive cases in Thai patients with CIU, to identify factors related to the positivity of ASST and to find the clinical implications of ASST in CIU. A retrospective study was performed among 85 CIU patients who attended the Urticaria Clinic at the Department of Dermatology, Siriraj Hospital and were willing to perform ASST, from January 2002 to December 2003. Twenty-one (24.7%) patients had a positive ASST. There was no significant difference between patients with positive ASST and negative ASST as to the severity of the disease (wheal numbers, wheal size, itching scores and the extent of body involvement) as well as the duration of the disease. PMID- 17348241 TI - Relevance of serum IgE estimation in allergic bronchial asthma with special reference to food allergy. AB - Studies suggest the importance of serum total and specific IgE in clinical evaluation of allergic manifestations. Such studies are lacking in Indian subcontinent, though a large population suffer from bronchial asthma. Here relevance of serum total and specific IgE was investigated in asthmatics with food sensitization. A total of 216 consecutive patients (mean age 31.9 years, S.D. 11.8) were screened by various diagnostic testing. Out of 216 patients, 172 were with elevated serum total IgE (201 to > 800 IU/ml). Rice elicited marked positive skin prick test reactions (SPT) in 24 (11%) asthma patients followed by black gram 22 (10%), lentil 21 (9.7%) and citrus fruits 20 (9.2%). Serum total IgE and specific IgE showed significant correlation, p = 0.005 and p = 0.001, respectively, with positive skin tests. Blinded food challenges (DBPCFC) with rice and or black gram confirmed food sensitization in 28-37% of cases. In summary, serum total IgE of 265 IU/ml or more with marked positive SPT (4 mm or more) can serve as marker for atopy and food sensitization. Specific IgE, three times of normal controls correlates well with positive DBPCFC and offers evidence for the cases of food allergy. PMID- 17348243 TI - Association of TNF-alpha, TNF-beta, IFN-gamma and IL-1Ra gene polymorphisms with Graves' disease in the Thai population. AB - Cytokines play a key role in the regulation of immune and inflammatory responses. Therefore, cytokine genes are potentially related to susceptibility to Graves' disease (GD). The aim of this study was to investigate the putative functional polymorphisms within tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor-beta (TNF-beta), interferon-gamma (IFN-gamma), and interleukin-1 receptor antagonist (IL-1Ra) genes, in patients with GD (n = 137) compared to a healthy Thai control group (n = 137). The results showed no statistically significant difference between the study groups for TNF-beta (Ncol site in intron 1), IFN gamma (+874 in intron 1), and IL-1Ra (variable numbers of tandem repeats in intron 2) gene polymorphisms. Only the -863A allele within the promoter region of the TNF-alpha gene, which may affect the affinity of the promoter nuclear factor (NF)-kappab interaction, was found to be increased in GD patients compared to the controls (p = 0.009, OR = 1.8, 95% CI = 1.15 to 2.84). The effect of the -863A allele of the TNF-alpha gene was similar to the autosomal dominance mode of inheritance (p = 0.01, OR = 2, 95% CI = 1.16 to 3.44). This polymorphism may be involved in the susceptibility to GD in part through its higher promoter activity of TNF-alpha production. PMID- 17348244 TI - Sicca symptoms in Thai patients with rheumatoid arthritis, systemic lupus erythematosus and scleroderma: a comparison with age-matched controls and correlation with disease variables. AB - This study was performed to determine the prevalence of ocular and oral sicca symptoms in Thai patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma (Scl). The ocular symptoms and sign (the Schirmer's 1 test) and the oral sicca symptoms and sign (the Saxon's test) in each of 50 RA, SLE and Scl patients were compared with their age-matched controls. The correlation between the presence of sicca symptoms and signs with their clinical activity was also determined. Ocular sicca symptoms were found more common in patients with RA (38% vs 18%, p < 0.05), SLE (36% vs 14%, p < 0.05) and Scl (54% vs 16%, p < 0.01), and oral sicca symptoms were found more common in SLE (22% vs 0%, p < 0.01), and Scl (16% vs 4%, p < 0.05) than their controls. However, only RA patients had a significantly higher proportion of positive Schimer-1 test compared with their controls (p < 0.01). There was no strong correlation between sicca symptoms or signs and other clinical or laboratory variables (age, disease duration, disease activity, disease severity, and antibody to Ro and La antigens) in these three groups. In conclusion, sicca symptoms were seen significantly more common in Thai patients with connective tissue diseases, but the symptoms did not show a good correlation with the clinical and laboratory variables. PMID- 17348245 TI - The effects of Porphyromonas gingivalis LPS and Actinobacillus actinomycetemcomitans LPS on human dendritic cells in vitro, and in a mouse model in vivo. AB - Interaction between different bacterial plaque pathogens and dendritic cells may induce different types of T helper (Th) cell response, which is critical in the pathogenesis of periodontitis. In this study we investigated the effects of lipopolysaccharide (LPS) from Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans on human monocyte-derived dendritic cells (Mo-DCs) with respect to co-stimulatory molecule expression, cytokine production and Th cell differentiation. Unlike Escherichia coli and A. actinomycetemcomitans LPS, P. gingivalis LPS induced only low levels of CD40, CD80, HLA-DR and CD83 expression on Mo-DCs. LPS from both bacteria induced considerably lower TNF-alpha and IL-10 than did E. coli LPS. LPS from all three bacteria induced only negligible IL-12 production. In a human mixed-leukocyte reaction, and in an ovalbumin-specific T cell response assay in mice, both types of LPS suppressed IFN-gamma production. In conclusion, stimulation by P. gingivalis LPS and A. actinomycetemcomitans LPS appears to bias Mo-DCs towards Th2 production. PMID- 17348246 TI - Traffic of antibody-secreting cells after immunization with a liposome associated, CpG-ODN-adjuvanted oral cholera vaccine. AB - An oral cholera vaccine made up of heat-treated recombinant cholera toxin (rCT), V. cholerae lipopolysaccharide (LPS), and recombinant toxin-co-regulated pili subunit A (rTcpA), entrapped in liposomes in the presence of unmethylated bacterial CpG-DNA (ODN#1826) was used to orally immunize a group of eight week old rats. A booster dose was given 14 days later. Control rats received placebo (vaccine diluent). The kinetics of the immune response were investigated by enumerating the antigen specific-antibody secreting cells (ASC) in the blood circulation and intestinal lamina propria using the ELISPOT assay and a histo immunofluorescence assay (IFA), respectively. ASC of all antigenic specificities were detected in the blood of the vaccinated rats as early as two days after the booster dose. The numbers of LPS-ASC and TcpA-ASC in the blood were at their peak at day 3 post booster while the number of CT-ASC was highest at day 4 after the booster immunization. At day 13 post immunization, no ASC were detected in the blood. A several fold increase in the number of ASC of all antigenic specificities in the lamina propria above the background numbers of the control animals were found in all vaccinated rats at days 6 and 13 post booster (earlier and later time points were not studied). Vibriocidal antibody and specific antibodies to CT, LPS and TcpA were detected in 57.1% and 52.4%, 14.3%, and 19.0% of the orally vaccinated rats, respectively. The data indicated that rats orally primed with the vaccine could produce a rapid anamnestic response after re exposure to the V. cholerae antigens. Thus, a single dose of the vaccine is expected to elicit a similar anamnestic immune response in people from cholera endemic areas who have been naturally primed to V. cholerae antigens, while two doses at a 14 day interval should be adequate for a traveler to a disease endemicarea. PMID- 17348247 TI - Mycobacterium avium and Burkholderia pseudomallei (Melioidosis) coinfection in an HIV-positive patient. AB - A 29 year old HIV positive Thai female with CD4 count of 10 cells/mm3 presented with chronic diffuse abdominal pain, fever, weight loss, anemia and leucopenia. Ultrasonography demonstrated diffuse upper abdominal lymphadenopathy with ascites. Microbiological and molecular work up of the specimen obtained by ultrasound-guided lymph node aspiration revealed co-infection with Burkholderia pseudomallei and Mycobacterium avium. Indirect hemagglutination, IgM-indirect fluorescent antibody, and IgG-indirect fluorescent antibody to Burkholderia pseudomallei were < 1:20, < 1:50 and < 1:50, respectively, at nine months, four months before the culture diagnosis and two months, eight months after the culture diagnosis of Burkholderia pseudomallei infection. The patient was treated initially with two weeks of intravenous ceftazidime, followed by oral cotrimoxazole, doxycycline and chloramphenicol. Clarithromycin and ofloxacin were added after the identification of Mycobacterium avium and its susceptibility test. The patients demonstrated clinical improvement with decreasing abdominal pain and resolution of fever. PMID- 17348248 TI - Simultaneous complication of multiple myeloma with Sjogren syndrome. AB - We report a 72-year-old female case of IgG-kappa type multiple myeloma (MM) simultaneously complicated with Sjogren syndrome (SS). She also presented marked hyperamylasemia of salivary-type isozyme. Although she had received sequential chemotherapy completed with high-dose therapy with autologous hematopoietic stem cell transplantation, she died of relapse fifteen months after the initial diagnosis. Various autoantibodies indicated that her sicca symptoms were due to true SS and not caused by MM cell infiltration to exocrine glands. MM cells appeared to produce amylase that fluctuated correspondingly to the disease status of MM. To our knowledge, this is the first English report of simultaneous complication of SS and MM referring to hyperamylasemia. Accumulation of this rare clinical manifestation is important to elucidate the pathogenesis of MM under condition of immunological disorder caused by SS. PMID- 17348249 TI - Must we always respect religious belief? PMID- 17348250 TI - The price of compromise: the Massachusetts health care reform. PMID- 17348251 TI - The price of compromise: the Massachusetts health care reform. PMID- 17348252 TI - The U.S. Department of Medicine. PMID- 17348253 TI - At the Lok Nayak Hospital, Delhi. PMID- 17348254 TI - Void for vagueness. PMID- 17348255 TI - Examining the provisions for research without consent in the emergency setting. PMID- 17348256 TI - Resuscitating a bad patient. PMID- 17348258 TI - "Nanoethics"? What's new? PMID- 17348257 TI - The new EPA regulations for protecting human subjects: haste makes waste. PMID- 17348260 TI - How turning a QI project into "research" almost sank a great program. PMID- 17348259 TI - Patents, biomedical research, and treatments: examining concerns, canvassing solutions. PMID- 17348261 TI - Unscientific ethics: science and selective ethics. PMID- 17348262 TI - Tales publicly allowed: competence, capacity, and religious belief. AB - What should we make of someone whose beliefs prevent her from accurately understanding her medical needs and care? Should that person still make her own health care decisions? In fact, she probably lacks decision-making capacity. But that does not mean she is not competent. PMID- 17348263 TI - Are alcoholics less deserving of liver transplants? AB - When does behavior trigger a lesser claim to medical resources? When does chronic drinking, for example, mean that one has a lesser claim to a liver transplant? Only when one's behavior becomes a callous indifference to others' needs--when one knows the consequences of heavy drinking and knows that by drinking one may end up depriving someone else of a liver. PMID- 17348264 TI - Discontinuing artificial fluids and nutrition: discussions with children' families. PMID- 17348265 TI - Implementing an EHR. Preparing for launch. PMID- 17348266 TI - Facts about paperless faxing. PMID- 17348267 TI - Malpractice consult. If the patient lacks capacity. PMID- 17348268 TI - Running a great meeting. PMID- 17348269 TI - Telephone triage. Can your staff answer the call? PMID- 17348270 TI - The ABCs of IMEs. An experienced hand reveals how to conduct independent medical exams. PMID- 17348271 TI - Taking dental health education to the next level. PMID- 17348272 TI - Osteonecrosis of the jaw. PMID- 17348273 TI - Maintenance products in tooth whitening. PMID- 17348274 TI - CAD/CAM restorations: aesthetic all-ceramics, predictable fit. AB - The Cercon Zirconia system has opened up new avenues of restorative possibilities for the clinician. This system provides extaordinary strength and beauty with the capability of providing long-span metal-free bridges as well as single crowns. The additon of Cercon Art with its consistency of fit has reduced some of the stresses associated with fabrication and fit issues for the dental technician, and the dentist is assured of delivering an aesthetic product with predictable restorative results. PMID- 17348275 TI - Current paradigm shifts in dentistry. AB - It is a time of revolution and innovation in dentistry. Many of the ongoing changes are significant, while others are less influential. I have discussed numerous observable and inevitable paradigm shifts. Dentists are advised to note the ongoing trends, become educated about them, evaluate the importance of the changes in their individual practices and to their patients, and to integrate these changes into practice. PMID- 17348276 TI - New directions in dental education. PMID- 17348277 TI - New directions in technology. PMID- 17348278 TI - Negotiating challenging mid root curvatures: rounding the bend. PMID- 17348279 TI - Access preparation endodontic: an opening for success. PMID- 17348280 TI - Accurate impression material and technique for well-adapted restorations. PMID- 17348281 TI - An expedited procedure for augmenting the alveolar ridge. PMID- 17348282 TI - Early childhood caries: taking treatment out of the hospital. PMID- 17348283 TI - A modern paradigm for caries management, part 1: diagnosis and treatment. PMID- 17348284 TI - Nonsyndromic supernumerary teeth: case report. PMID- 17348285 TI - New directions: the underpinnings of clinical excellence. PMID- 17348286 TI - How to increase patient acceptance for cosmetic dentistry: cosmetic imaging with Adobe Photoshop Elements 4.0. PMID- 17348287 TI - Mammalian model hosts of cryptococcal infection. AB - The rising incidence of serious fungal diseases represents a growing threat to human health. Cryptococcus neoformans, an encapsulated yeast saprophyte with global distribution, has been recognized as an important emerging pathogen. Humans frequently develop asymptomatic or mild infection with C. neoformans, but individuals with impaired host defense systems may develop severe pneumonia and potentially fatal meningoencephalitis. Insight into the biology and virulence of C. neoformans is advancing rapidly and will be propelled even further by the recently completed and published genome sequences for two related strains of C. neoformans serotype D. Several mammalian model hosts including the guinea pig, rabbit, rat, and mouse have been developed for the study of cryptococcosis. The combination of microbial genomics with well-characterized model hosts that are amenable to immunologic and genetic manipulation represents a powerful resource for comprehensive study of cryptococcal disease pathogenesis as well as vaccine and antifungal drug therapy. This review provides an introduction to each mammalian model host and briefly highlights the advantages, limitations, and potential of each system for future research involving cryptococci. PMID- 17348288 TI - Pathobiology and management of laboratory rodents administered CDC category A agents. AB - The Centers for Disease Control and Prevention Category A infectious agents include Bacillus anthracis (anthrax), Clostridium botulinum toxin (botulism), Yersinia pestis (plague), variola major virus (smallpox), Francisella tularensis (tularemia), and the filoviruses and arenaviruses that induce viral hemorrhagic fevers. These agents are regarded as having the greatest potential for adverse impact on public health and therefore are a focus of renewed attention in infectious disease research. Frequently rodent models are used to study the pathobiology of these agents. Although much is known regarding naturally occurring infections in humans, less is documented on the sources of exposures and potential risks of infection to researchers and animal care personnel after the administration of these hazardous substances to laboratory animals. Failure to appropriately manage the animals can result both in the creation of workplace hazards if human exposures occur and in disruption of the research if unintended animal exposures occur. Here we review representative Category A agents, with a focus on comparing the biologic effects in naturally infected humans and rodent models and on considerations specific to the management of infected rodent subjects. The information reviewed for each agent has been curated manually and stored in a unique Internet-based database system called HazARD (Hazards in Animal Research Database, http://helab.bioinformatics.med.umich.edu/hazard/) that is designed to assist researchers, administrators, safety officials, Institutional Biosafety Committees, and veterinary personnel seeking information on the management of risks associated with animal studies involving hazardous substances. PMID- 17348289 TI - Animal models for HIV AIDS: a comparative review. AB - Human immunodeficiency virus (HIV), the causative agent for acquired immune deficiency syndrome, was described over 25 y ago. Since that time, much progress has been made in characterizing the pathogenesis, etiology, transmission, and disease syndromes resulting from this devastating pathogen. However, despite decades of study by many investigators, basic questions about HIV biology still remain, and an effective prophylactic vaccine has not been developed. This review provides an overview of the viruses related to HIV that have been used in experimental animal models to improve our knowledge of lentiviral disease. Viruses discussed are grouped as causing (1) nonlentiviral immunodeficiency inducing diseases, (2) naturally occurring pathogenic infections, (3) experimentally induced lentiviral infections, and (4) nonpathogenic lentiviral infections. Each of these model types has provided unique contributions to our understanding of HIV disease; further, a comparative overview of these models both reinforces the unique attributes of each agent and provides a basis for describing elements of lentiviral disease that are similar across mammalian species. PMID- 17348290 TI - Murine gammaherpesvirus 68: a model for the study of Epstein-Barr virus infections and related diseases. AB - Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus (GHV) that causes acute infection and establishes life-long latency. EBV is associated with the development of B-cell lymphoproliferative disorders, several malignant cancers, the syndrome of infectious mononucleosis, and chronic interstitial lung disease. Although the molecular biology of EBV has been characterized extensively, the associated disease conditions and their pathogenesis are difficult to study in human populations because of variation in human environments and genetics, the well-documented effect of stressors on pathogenesis, and the chronic and latent properties of the virus. GHV are highly species-specific, and suitable animal models for EBV are not available. However, in 1980, a murine gammaherpesvirus (MuGHV, also known as MHV68 and gammaHV68) was identified as a natural pathogen of bank voles and wood mice. Experimental MuGHV infections in laboratory mice share many features of EBV infections in humans, including facets of the clinical human syndrome known as infectious mononucleosis. These features make MuGHV a valuable experimental model for studying the pathophysiology of a GHV in a natural host. PMID- 17348291 TI - Detection of mouse parvovirus in Mus musculus gametes, embryos, and ovarian tissues by polymerase chain reaction assay. AB - We used primary and nested polymerase chain reaction (PCR) assays to determine the presence of mouse parvovirus (MPV) in mouse sperm, oocytes, preimplantation embryos, and ovarian tissues collected from MPV-infected mice. The primary PCR assay detected MPV in 56% of the sperm samples. MPV was not eliminated by passing sperm samples through a Percoll gradient. After Percoll treatment, MPV was still present in 50% of the samples according to primary PCR assay. Oocyte samples that did not undergo extensive washing procedures had detectable MPV in 7% of the samples based on the primary PCR assay, but nested PCR assay detected higher (28%) infection rate. However, MPV was not detected in oocytes that underwent extensive washing procedures, as assessed by either primary or nested PCR assay. Although primary PCR did not detect MPV in embryos, a nested PCR assay determined that 50% of the embryos were positive for the virus. In addition, ovarian tissues were collected from 3 different mouse colonies with enzootic MPV infection. Ovarian tissue collected from 129CT, 101/R1, and Sencar mice had high incidence (38%, 63%, and 65%, respectively) of MPV infection on the basis of nested PCR amplification. These results demonstrate that mouse gametes, embryos, and ovarian tissues may be contaminated with MPV and therefore caution is necessary when infected germplasm is used for assisted reproductive technologies such as embryo transfer, establishing embryonic stem cell lines, in vitro fertilization, ovary transplantation, and intracytoplasmic sperm injection. PMID- 17348292 TI - A reproducible scoring system for quantification of histologic lesions of inflammatory disease in mouse gastric epithelium. AB - Comparison of experimental groups by microscopic examination is a common and useful method for evaluating animal models of disease. Quantification of lesions is challenging, however, and differences in scoring systems hinder comparison of results from different laboratories. The purpose of this study was to validate a simple and reproducible scoring system for Helicobacter pylori-associated gastric disease in mice. The system is based on quantification of the percentage of microscopic fields in which lesions are present, rather than on subjective estimates of lesion severity. Linear regression analyses revealed good agreement between investigators in scoring of all 3 histologic criteria examined. The range of correlation coefficients between individual readers' scores and mean scores for the 3 histologic criteria examined were: neutrophilic inflammation, 0.845 to 0.935; gastritis sufficient to displace glands, 0.919 to 0.943; and epithelial metaplasia, 0.650 to 0.799. Comparison of scores in different experimental groups by analysis of variance and Fisher least significant difference tests revealed significant differences between infected and uninfected groups and between immunodeficient and immunocompetent groups. We propose that this system may be useful in standardizing the morphologic evaluation of rodent models of H. pylori and that a similar system could be devised for evaluation of other animal models of enteric disease. PMID- 17348293 TI - Temporal transmission studies of mouse parvovirus 1 in BALB/c and C.B-17/Icr Prkdc(scid) mice. AB - Fecal shedding and transmission of mouse parvovirus 1 (MPV) to naive sentinels, breeding mates, and progeny were assessed. Neonatal SCID and BALB/c mice inoculated with MPV were evaluated over 24 wk; several mice from each strain were mated once during this period. Fecal MPV loads for each cage were determined weekly by quantitative polymerase chain reaction (PCR) analysis, and all mice were evaluated by quantitative PCR analysis of lymphoid tissues and seroconversion to MPV antigens in immunocompetent mice. Results indicated persistently high fecal shedding of MPV in SCID mice throughout the evaluation period sufficient to allow transmission to sentinels, naive breeding partners, and the progeny of infected male mice and naive partners. Lymphoid tissue viral loads in the progeny of infected female SCID mice were high at weaning but low at 6 wk of age. Infected BALB/c mice shed high levels of MPV in feces for 3 wk postinoculation, with seroconversion only in sentinels exposed during the first 2 wk postinoculation. Thereafter the feces of infected BALB/c mice and the lymphoid tissues of sentinels, naive breeding partners, and progeny intermittently contained extremely low levels of MPV DNA. Although pregnancy and lactation did not increase viral shedding in BALB/c mice, MPV exposure levels were sufficient to induce productive infection in some BALB/c progeny. These data indicate that the adaptive immune response suppresses, but does not eliminate, MPV shedding; this suppression is sufficient to inhibit infection of weanling and adult mice but allows productive infection of some progeny. PMID- 17348294 TI - Gender influences infectivity in C57BL/6 mice exposed to mouse minute virus. AB - Two natural outbreaks of mouse minute virus (MMV) are described. Observations during management of the naturally infected colonies led to a study in which 4-wk old C57BL/6NCr and C57BL/6Tac mice were inoculated oronasally with an immunosuppressive variant of MMV (MMVi), as were adult C57BL/6NCr lactating dams or their pups (age, 10 d). By day 28 postinoculation, 100% of the 4-wk-old male C57BL/6NCr and C57BL/6Tac mice, 56.2% of 4-wk-old C57BL/6NCr female and 62.5% of 4-wk-old C57BL/6Tac female mice, 100% of adult lactating C57BL/6NCr dams, and 100% of inoculated pups (10 d) had seroconverted. Serologically positive nursing dams did not infect their nursing pups. In contrast, when nursing pups were inoculated, 100% of their dams seroconverted by 28 d postinoculation. Only 1 of 4 facility sentinels (Tac:SW female mice) seroconverted to MMVi and none of the 4 research sentinels (Tac:SW female mice) seroconverted under a once-weekly bedding transfer program. Consequently, 4 new research Tac:SW sentinels of each gender (n = 8) were placed in known-positive cages at cage-change; 100% of the male mice but 0% of the females seroconverted by day 48. Study results suggest gender influences both infectivity and the ability to detect subclinical infections of MMVi. Other factors that may influence detection of MMV include mouse strain or stock, short shedding period, and prolonged time between cage changes. In light of the data from both the natural infections and the experimental cases, cessation of breeding likely will be beneficial when trying to eradicate this virus. PMID- 17348296 TI - Reliability of soiled bedding transfer for detection of mouse parvovirus and mouse hepatitis virus. AB - Serologic monitoring of sentinel mice exposed to soiled bedding is a common method of detecting viral infections in mice. Because bedding transfer protocols vary, the sensitivity of this method has not been documented sufficiently. We examined the reliability of bedding transfer during various stages of infection with mouse parvovirus (MPV) and mouse hepatitis virus (MHV). Most mice exposed to bedding contaminated with MPV 0, 3, or 7 d previously seroconverted, whereas only mice exposed to bedding contaminated with MHV 4 h previously seroconverted, thus confirming the differing stabilities of these viruses. Index mice were inoculated with 30 times the infectious dose 50 (ID50) of MPV or 300 ID50 of MHV. At 3 d, 1 wk, and 2 wk postinoculation (PI), we transferred 25, 50, or 100 ml of bedding to cages of sentinel mice. Viral infection and shedding by index mice was confirmed by serology and fecal polymerase chain reaction assay. Transfer of soiled bedding between mice in static cages induced seroconversion of sentinel mice most reliably during peak viral shedding (1 wk PI for MPV and 3 d PI for MHV). Soiled bedding transfer between mice in individually ventilated cages induced a higher prevalence of sentinel seroconversion to MPV and MHV than that after transfer between mice in static cages. Our findings indicate that although soiled bedding transfer is an effective method for detecting MHV and MPV under optimal conditions, the method is less than 100% reliable under many conditions in contemporary mouse facilities. PMID- 17348295 TI - Induction of pro- and anti-inflammatory molecules in a mouse model of pneumococcal pneumonia after influenza. AB - Mortality after influenza is often due to secondary bacterial pneumonia with Streptococcus pneumoniae, particularly in the elderly. The reasons for the high fatality rate seen with this disease are unclear. To further characterize the pathogenesis of pneumonia after influenza in a mouse model, we examined the pathology and immunology that leads to fatal infection. Influenza-infected mice were either euthanized 24 h after secondary infection with S. pneumoniae for determination of pathology, bacterial cultures, and levels of immune effectors or were followed by use of a live imaging system for development of pneumonia. Influenza-infected mice challenged with each of 3 serotypes of pneumococcus developed a severe, necrotic pneumonia and met endpoints for euthanasia in 24 to 60 h. Strikingly elevated levels of both pro- and anti-inflammatory molecules including interleukins 6 and 10, macrophage inflammatory protein 1alpha, and chemokine KC were present in the blood. High levels of these cytokines and chemokines as well as tumor necrosis factor alpha, interleukin 1beta, and heme oxygenase 1 were present in the lungs, accompanied by a massive influx of neutrophils. Mortality correlated with the development of pneumonia and lung inflammation but not with bacteremia. This model has the potential to help us understand the pathogenesis of severe lung infections. PMID- 17348297 TI - Newly identified Mycobacterium species in a Xenopus laevis colony. AB - The University of Massachusetts Medical School maintains 3 separate research colonies of Xenopus laevis, with each colony located in a separate building on campus. After a 5-wk in-house quarantine period, 34 wild-caught X. laevis were transferred into one of the existing colonies. As a result, this colony grew from 51 to 85 frogs. All animals were housed in a recirculating frog housing system. During the first 2 mo, 6 frogs died suddenly, and health reports were generated for another 10 frogs in this colony. The majority of health reports were written in response to acute coelomic distention. These patterns continued until, after 1 y, only 25 of the original 85 animals remained. Necropsies performed showed large accumulations of serosanguinous fluid in the subcutaneous space or body cavity. Granulomatous inflammatory lesions with acid-fast bacilli were generally present in the liver, lung, or spleen. Culture of affected tissues grew Mycobacterium sp. within 40 d. Polymerase chain reaction analysis confirmed the isolated organism to be the same species of Mycobacterium (provisionally named M. liflandii) recently reported by 2 other groups. However, previous clinical publications suggested that this bacterium originated only from X. tropicalis. The cases we present highlight the rapidly lethal effects of M. liflandii in a colony of wild caught X. laevis and illustrate the need to dedicate further attention to this emerging Xenopus disease. PMID- 17348298 TI - Transmission dynamics of simian T-lymphotropic virus type 1 (STLV1) in a baboon breeding colony: predominance of female-to-female transmission. AB - We investigated the prevalence, distribution, and transmission of simian T lymphotropic virus type 1 (STLV1) in a baboon breeding colony over a 4-y period. We used polymerase chain reaction amplification of the proviral tax gene to assess the infection status of 272 animals housed in 4 separate corrals. Sequencing the proviral envelope gene from individual baboons detected several molecular subtypes (genotypes) of STLV1. At the start of the study, 31% (54 of 176) of all baboons were infected; the majority of infections (91%) were in mature females, with only 3 of 12 mature males and 2 of 48 infants and juveniles being infected. Over the next 4 years, 41 new infections were diagnosed. Of these, 83% occurred in sexually mature female baboons (at least 3 y of age), 17% in infants and juveniles (younger than 3 y), and 0% in mature males. The 7 infections in juveniles were probably derived from mother-to-infant transmission because mother-infant pairs consistently were infected with the same viral genotype. Of the 34 new infections in sexually mature female baboons, the genotyping data showed that 25 (73%) originated from other infected females as opposed to males. Male-to-female sexual transmission may have accounted for the remaining 9 new infections. There was no evidence of female-to-male sexual transmission. The high percentage of female-to-female transmission of STLV1 in our baboons was unexpected; we speculate that transmission may have occurred due to blood contamination from biting during aggressive behavior between females in establishing hierarchical dominance. PMID- 17348299 TI - Seroprevalence of West Nile virus in nonhuman primates as related to mosquito abundance at two national primate research centers. AB - West Nile virus (WNV) surfaced as an emerging infectious disease in the northeastern United States in 1999, gradually spread across the continent, and is now endemic throughout North America. Outdoor-housed nonhuman primates at the Tulane National Primate Research Center (TNPRC) in Louisiana were documented with a relatively high prevalence (36%) of antibodies to West Nile virus. We examined the prevalence of antibodies to WNV in a nonhuman primate population housed in outdoor colonies at the Yerkes National Primate Research Center Field Station located near Atlanta, Georgia. We screened rhesus macaques (Macaca mulatta) and sooty mangabeys (Cercocebus atys) that were at least 3 y old by serum neutralization for antibodies to WNV and confirmed these results by hemagglutination-inhibition assay. None of the 45 rhesus monkeys had antibodies to WNV, but 3 of the 45 mangabeys (6.6%) were positive by both serum neutralization and hemagglutination-inhibition tests. The ratio of seroprevalences in the TNPRC and Yerkes primate populations was similar to the ratio of WNV incidences in people in Louisiana and Georgia from 2002 to 2004. The difference in the exposure of nonhuman primates (and possibly humans) to WNV between these 2 regions is consistent with the difference in the abundance of mammal-biting WNV-infectious mosquitoes, which was 23 times lower near Yerkes than around TNPRC in 2003 and 33 times lower in 2004. PMID- 17348300 TI - Changes in the titer of anti-B virus antibody in captive macaques (Macaca fuscata, M. mulatta, M. fascicularis). AB - Changes in levels of antibody to B virus (Cercopithecine herpesvirus 1; BV) were examined in BV-positive macaques by ELISA. We observed increases in anti-BV IgG titers in a BV-infected cynomolgus monkey after overseas transportation by air and in a rhesus monkey after transfer from an outdoor group cage to an indoor individual cage. Although shedding of infectious virus was not examined, the increase in antibody titer suggested reactivation of BV. Interestingly, we also found an increase in anti-BV IgG levels during the breeding season in male but not female Japanese macaques kept in an enclosed outdoor colony. Further studies should be performed to investigate whether reactivation of BV led to the observed increase in the anti-BV antibody titer. PMID- 17348301 TI - Naturally occurring Tyzzer's disease in cotton-top tamarins (Saguinus oedipus). AB - We noted naturally occurring infection with Clostridium piliforme (Tyzzer's disease) in 2 captive-reared cotton-top tamarins (Saguinus oedipus). Spontaneous Tyzzer's disease has been reported in multiple species of laboratory, domestic, and wild animals but is extremely rare in humans and nonhuman primates. Distinct from idiopathic colitis, which is common in cotton-top tamarins, these 2 tamarins had severe, transmural, necrotizing typhlocolitis accompanied by myocarditis and hepatitis. Abundant bacteria compatible with C. piliforme, the etiologic agent of Tyzzer's disease, were present adjacent to lesions in the cecum-colon, liver, and heart. Therefore, colitis caused by C. piliforme, although rare, should be included as a differential diagnosis in cotton-top tamarins and as a cause of postnatal mortality in this species. PMID- 17348302 TI - Malignant tuberculosis. PMID- 17348303 TI - Adult intussusception--a surgical dilemma. AB - BACKGROUND: Adult intussusception is rare. It is expected to be found in 1/30,000 of all hospital admissions, 1/1300 of all abdominal operations, 1/30-1/100 of all cases operated for intestinal obstruction and one case of adult intussusception for every 20 childhood ones. METHODS: The authors encountered 4 cases of adult intussusception. M:F ratio was 1:1. Mean age was 47years. Small bowel obstruction was documented in all. They were investigated by radiographs, ultrasound exam, barium studies, endoscopy and CT scan. RESULTS: All however were diagnosed at operation although some pre-operative suspicion was raised in one case. All had a laparotomy. Two were ileo-ileal and two ileo-caecal intussusceptions. One was chronic intussusceptions and three sub-acute. One intussusception had a malignancy (lymphoma) as a lead point. Two had a submucous lipoma at the apex. In an interesting case the suture knot from a recent small bowel anastomosis (2-3 weeks prior) was forming the lead point of the intussusception! The 2 ileo-ileal intussusceptions had segmental resection. Right hemicolectomy was done for the 2 ileo-caecal cases. "Target lesion" and leumen-within-leumen were the CT hallmarks on review. Retrospective barium enema review failed to show the intussusception. This may suggest the intussusception may have been recurrent or chronic. All 4 recovered uneventfully and remained well. One patient was referred for chemotherapy for intestinal lymphoma. CONCLUSION: Adult intussusception remains a rare cause of abdominal pain. The treatment almost always is surgical. PMID- 17348304 TI - Comparative cellular immune host response in acute vs healed lesions of cutaneous leishmaniasis. AB - BACKGROUND: Cutaneous leishmaniasis (CL) has become a major public health problem in Pakistan and research is now focused to characterize the host's immune response, its clinical correlation and subsequent implications in management in this disease. This study was done to evaluate cellular immune host response in patients with active and healed CL and its possible implications in prevention of disease in susceptibles. METHODS: This cross sectional and comparative study was conducted in Armed Forces Institute of Pathology (AFIP) and Military Hospital (MH) Rawalpindi (1998-2000). 30 biopsies of active skin lesions and 15 biopsies from healed lesions, after processing, were studied for various immunophenotype cells by using monoclonal antibodies. Total and differential T cell counts were recorded in these skin tissues. Non parametric Kruskal-Wallis Test for one way ANOVA was used to compare the median cell counts between active, healed and normal skin and p-value < 0.05 was considered significant. RESULTS: The total cell counts, CD3+ cells and CD57+ (NK) cells were found statistically different (p = < 0.001) when active forms of the disease were compared with healed lesions and normal skin tissue. The difference was not significant (p = > 0.05) on comparing healed lesions with normal skin tissue biopsies except in case of CD3+ cell counts (p = < 0.05). However, CD4+, CD8+ and CD19+ (Plasma cells) counts were never seen significant (p = > 0.05) on comparison. CONCLUSION: NK cells and gamma delta cells seem to be responsible for limitation of the disease and elimination of the parasite from the lesion in cases of acute cutaneous leishmaniasis. PMID- 17348305 TI - A study on functional similarity between dengue non structural protein 1 and platelet integrin/adhesin protein, CD61. AB - BACKGROUND: Dengue infection is a major public health problem. The mechanisms underlying severe bleeding in dengue DHF are not completely understood. It was proposed that the dengue virus nonstructural-1 protein (DNS1) generated antibodies to common epitopes on human blood clotting and integrin/adhesin proteins on the platelet. The proof on the functional correlation between DNS1 and platelet integrin/adhesin proteins is needed. METHODS: Here, the author used a new gene ontology technology to predict the molecular function and biological process of DNS1 and platelet integrin/adhesin protein, CD61. RESULT: According to this study, the author can identify no function and biological process of DNS1. Also, there is no existence of functional similarity between DNS1 and CD61. CONCLUSION: The hypothesis on role of molecular mimicry between DNS1 and CD61 is not supported in this study. PMID- 17348306 TI - Influence of steroid hormones in women with mild catamenial epilepsy. AB - BACKGROUND: In view of considerable differences of opinion regarding the reproductive steroid hormonal pathogenesis in catamenial epilepsy, hormonal analysis of estrogen and progesterone in catamenial epileptics for a precise correlation is of significant importance. METHODS: Clinical, neurological and physiological assessments, and radioimmunoassay of plasma estradiol-17beta and progesterone a day prior to the onset of menstruation were carried out in noncatamenial and mild catamenial epileptics having multiple frequency tonic clonic (primary and secondary generalized) seizures. RESULTS: Highly significant rise (p > 0.0001) of estradiol-17beta was obtained for catamenial epileptics compared to normal subjects as well as noncatamenial epileptics (p > 0.02). However, nonsignificant fluctuations of progesterone were found for both catamenial and noncatamenial epileptics against normal subjects as well as catamenial versus noncatamenial epileptics. CONCLUSIONS: The present report suggests that estradiol have a precise role in the mild premenstrual exacerbation of seizures. However, no significant change in progesterone levels might have been due to mild exacerbation of seizures in these patients. Furthermore, we suggest the importance of how we collect and categorize the data and which pathophysiologic process/ clinicobiological mechanism is involved in patients with catamenial epilepsy. Contradictory results in literature may be related to differential levels of excitation/inhibition equilibrium during various cycle phases. More precise studies including the determination of the blood levels of antiepileptic drugs, however, are required. PMID- 17348307 TI - Comparison of frequency of wound infection: open vs laparoscopic cholecystectomy. AB - BACKGROUND: The objective of this quasi experimental study was to compare the frequency of wound infection between open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) conducted in Surgical Unit IV, Jinnah Hospital Lahore from June 2005 to January 2006. METHODS: 100 patients undergoing elective cholecystectomy for symptomatic gallstones were studied. The patients were allocated in the two groups of 50 each by simple random technique. Group-I underwent OC and Group-II underwent LC. The patients were then followed up for four weeks to pick up signs of wound infection. In case of infection, the degree of infection and the remedial measures done were documented and the results analysed. RESULTS: In LC group there was only one case of Class-II wound infection i.e. 2%. In case of OC there were three cases of wound infection i.e. 6%. Out of these, two were of Class-IIl and one of Class-Il. CONCLUSION: While there was no wound infection in cases of chronic Cholecystitis in both groups, the frequency of wound infection was three times as common in OC as compared to LC in Acute Cholecystitis/Empyema. PMID- 17348308 TI - Chilblains at Abbottabad, a moderately cold weather station. AB - BACKGROUND: Chilblains are quite often seen in various parts, in particular cold weather areas of Pakistan. Unfortunately, no studies have so far been carried out in Pakistan, to determine epidemiological aspects of chilblains. The objective of this study was to see the epidemiological patterns of chilblains at a moderately cold weather station. METHODS: The study was conducted at Dermatology out patient department of Combined Military Hospital, Abbottabad from 1 Dec 2004 to 31 Mar 2005. All the patients fulfilling clinical criteria for the diagnosis of chilblains were registered. Every patient was interviewed in detail followed by thorough physical examination. Complete Blood Count, Urine Routine Examination and Anti Nuclear Factor were carried out in only those patients, having the disease of more than 3 years duration. A pre-designed proforma was filled separately for each patient. RESULTS: Out of 111 patients, 67 (60.4%) males and 44 (39.6%) females were registered with the diagnosis of chilblains. Fifty nine (53.2%) patients were locals and 52 (46.8%) were non locals. Out door workers were 75 (67.6%). Onset in majority of the patients (42.3%) was in the age group 11-20 years. Family history of chilblains was present in 25 (22.5%) patients and 8 patients (7.2%) were smokers. The disease of longer duration was more common in females and locals. CONCLUSION: At moderately cold weather areas, out door workers and young adolescents are more likely to develop Chilblains. The disease of longer duration is more common among females and local residents. On the other hand, first episode or the disease of shorter duration is more common among non locals at moderately cold weather stations because of poor acclimatization and inadequate protection. PMID- 17348309 TI - Histological changes in parts of foregut of rat after indomethacin administration. AB - BACKGROUND: Indomethacin, a non-steriodalanti-inflammatory drug, is used mainly for the treatment of painful joints such as rehumatoid arthritis, osteo arhtritis, gout, ankylosing spondylitis etc. It relieves pain, reduces swelling and tenderness of the joints. It also induces ulceration of stomach and small intestine both in experimental animals and humans. MATERIAL AND METHODS: In this study indomethacin was given intrapertioneally in maximum therapeutic dose (4 mg/Kg body weight) to three experimental groups B, C and D for one, two and three weeks respectively. Group A was the control group. RESULTS: Effects were observed in stomach pylorus and proximal duodenum. In the stomach pylorus, well defined superficial ulcers were identified during initial two weeks of drug administration. The ulcer penetrated as for as muscularis mucosae and ulcer bed had coagulative necrosis and inflammatory cells. During third week, stomach pylorus showed minor damage in the form of focal necrosis. Duodenum was affected less than stomach and showed villi with lost tips, tilted and distorted villi. Morphometric analysis showed changes in stomach pylorus and in duodenum. The number of mitotic figure was significantly increased in stomach pylorus. Duodenum showed insignificant to significant decrease in the height of villi. Increase in the number of goblet cells, columnar cells, and mitotic figure was also noted; which was undoubtedly part of the tissue response to an injury. CONCLUSION: These observations suggested that indomethacin given in a maximum therapeutic dose, initially induces lesions in stomach pylorus and proximal duodenum but almost no effects were noted when duration of the drug administration was prolonged. PMID- 17348310 TI - Use of Foley's catheter and prostaglandin F-2 alpha in second trimester termination of pregnancy. AB - BACKGROUND: Termination of pregnancy (TOP) in the second trimester is associated with three to five times higher risk of maternal morbidity and mortality than termination during first trimester. The main concern of obstetrician is to provide the most effective and safest regimen which combines the shortest expulsion interval with least side effects. This study was undertaken to compare the use of Foley's catheter with extra-amniotic instillation of PGF2 alpha for second trimester TOP so that a choice of the safer and cost-effective method could be available. METHODOLOGY: The study was conducted in Department of Obstetrics and Gynecology Unit 'B' at Ayub Teaching Hospital Abbottabad between August 2003 and July 2004. Sixty patients recommended for TOP (missed abortion or anencephalic fetus confirmed on ultrasonography) were randomly allocated into two groups. In group 'A', Foley's catheter alone was used while in group 'B' extra amniotic instillation of Prostaglandin F-2 alpha (PGF2 alpha) was done via a Foley's catheter. After expulsion of catheters in both cases oxytocin infusion containing 30 units were started till the expulsion of fetus, placenta and membranes. The mean induction to expulsion time and the mean induction to delivery time for both groups were noted as well as total cost of treatment. RESULTS: Difference in time interval with regard to induction to expulsion time of catheter and induction to delivery time between the two groups was significant being 3 hours and 5 hours respectively less in group 'B' (p < 0.001); however only 25% of patients in group 'B' had a significant short induction to delivery time as compared to group 'A'. The difference in costs of treatment between the groups was also significant (p < 0.001). CONCLUSION: Use of PGF2 alpha is preferred, though for poor patients Foley's catheter may be used, but only in a tertiary care setting. PMID- 17348311 TI - Prevalence of diabetic retinopathy among individuals screened positive for diabetes in five community-based eye camps in northern Karachi, Pakistan. AB - BACKGROUND: Population-based data on the prevalence of diabetic retinopathy in Pakistan are lacking. We determined the prevalence of diabetic retinopathy among individuals screened positive for diabetes in five community-based eye camps in northern Karachi, Pakistan. METHODS: In summer 2002, five community-based eye camps were set up in Karachi, Pakistan's largest city. All individuals aged 30 years or older who visited the camps were requested to participate in the study. Those who agreed were screened for diabetes and those found to have the disease were referred to an eye hospital for diabetic retinopathy screening. Verbal informed consent was obtained from all participants at the examination site. Our main outcome measure was diabetic retinopathy, which was classified as non proliferative diabetic retinopathy (NPDR), severe NPDR, and proliferative diabetic retinopathy (PDR). Our grading was based on clinical examination. RESULTS: A total of 912 subjects were screened for diabetes mellitus. Of these, 160 (17.5%) had diabetes- 1.8% had type I diabetes and 15.9% had type II diabetes. One hundred and eight individuals visited the hospital for ophthalmic examination. Of them, 15.7% had diabetic retinopathy. The prevalence of diabetic retinopathy was higher among individuals with type I diabetes, with greater duration of diabetes, and among women. The commonest form of diabetic retinopathy was non-proliferative (76.5% [mild: 35.3%, moderate: 29.4%, and severe: 11.8%]), followed by maculopathy (17.6%) and proliferative diabetic retinopathy (5.9%). CONCLUSION: More systematic and population-based research is needed to estimate the prevalence of and identify risk factors for diabetic retinopathy in Pakistan. PMID- 17348312 TI - Malaria in children: study of 160 cases at a private clinic in Mansehra. AB - BACKGROUND: This study was conducted in a private clinic to report frequency, presentation and management of malaria in children presenting with fever. METHODS: 160 Children of age varying from 42 days to 15 years were included in this study, during a period of 1999-2004. RESULTS AND CONCLUSIONS: Malaria was confirmed in 154 cases, including 114 male and 46 female children. In 6 cases malarial parasite was not seen on microscopic examination of their blood films. 142 cases were found to be suffering from vivax and 12 were suffering from falciparum malaria. Most of the cases were treated with amodiaquine and some of them were treated with other antimalarial drugs. PMID- 17348313 TI - Stigma and psychiatric illness. A survey of attitude of medical students and doctors in Lahore, Pakistan. AB - BACKGROUND: The stigma attached to mental illness in the West is now well recognised. There is however, only limited information available on this topic from the developing countries. Measurement of stigma among medical students and doctors is straightforward to carry out allowing targeted work to educate doctors in countries with few resources. This study was carried out to assess the attitude of medical students and doctors, attending medical colleges in Lahore, Pakistan. METHODS: A survey was circulated among the medical students and the doctors of the three medical colleges in Lahore, Pakistan. 294 (59%) of the 500 survey forms sent out were returned. RESULTS: Just over half of the respondents held negative attitudes towards people with schizophrenia, depression, drug and alcohol disorders. However, most had favourable views of the recovery and treatability of the mental disorders. CONCLUSIONS: The views held by the medical students and the doctors in Lahore, Pakistan are broadly similar to the opinions expressed by the medical students and doctors in the UK. PMID- 17348314 TI - Effect of ciprofoxacin on growing cartilage in albino rat pups. AB - BACKGROUND: Administration of quinolone therapy is controversial during growing age as stated by earlier worker. The flroquinolones are currently not indicated for young children, because of arthropathy and adverse effect on growing cartilage shown by studies. However the effects of ciprofloxacin on epiphyseal growth plate has remained undocumented. This study is therefore, undertaken to determine the risk of ciprofloxacin administration an growing cartilage by prospective experimental animal study model using Wistar albino rat pups. METHODS: Ciprofloxacin was administered to newly born Wistar albino rat pups with a doze of 20 mg/kg body weight intraperitonealy twice a day from day-1 to day-14 after birth. The animals were sacrificed by deep ether anesthesia. The limbs were disarticulated from axial skeleton, soft tissue was removed. The intact bone mean length in millimeter of right and left humerus and femur was measured with the help of electronic vernier caliper and bones were fixed in 10% buffered farmalin. Decalcification was done in 10% nitric acid and 10% formic acid changes. After paraplast embeding, 4 microm thick longitudinal sections of the proximal long bones were cut by a rotary microtome. Routine staining with haemotoxylin and eosin was performed. Histomorphometry was done measuring the thickness of epiphyseal cartilage and was compared with similar value of control animals. The results were statistically analysed to find out the significance. RESULTS: The ciprofloxacin induces a mordanting effect as abviated by increased basophilia. Our study reveales that cirprofloxacin administration in the newly born pups decreased the width of epiphyseal growth plate cartilage by 10.43% in humerus and 4.72% in femur as compared to the growth of control cartilage. The decrease in the width was brought about mainly by the reduced count of the proliferative cells in the proliferative zone and the diminuation in the average size of the hypertrophic condryocytes in the hypertrophic zone. The reserve zone has become markedly reduced in thickness. CONCLUSION: The ciprofloxacin post-natal administration effected growth plate retardation by inhibiting the mitosis in the proliferative zone and also effected the mean length of humora and femora leading to reduction in limb length of rat pups. PMID- 17348315 TI - Attitude of the university students and teachers towards mentally ill, in Lahore, Pakistan. AB - BACKGROUND: Although, much is known about the attitudes and beliefs people hold towards mental illness in the west, no such work has been done in the developing countries. It is difficult to measure the attitudes of the general public in developing countries due to differences in terminology and concepts of the illness. However, majority of educated people in the developing countries can recognise common psychiatric disorders by their western names. We therefore, decided to measure attitudes of university students and teachers in Lahore, Pakistan. This study was carried out to assess the attitude of university students and teachers in Lahore, Pakistan. METHODS: A survey form was circulated among the university students and the teachers in Lahore, Pakistan. Of the 300 survey forms 194 were returned. RESULTS: Majority of the respondents held negative attitudes towards people with schizophrenia, depression and drug and alcohol disorders. CONCLUSIONS: The views held by the university teachers and students reveal negative attitudes towards mentally ill. Attitudes of those who knew someone with mental illness were similar to those who did not. PMID- 17348316 TI - An experience of 42 cases of bronchoscopy at Saidu Group of Teaching Hospitals, Swat. AB - BACKGROUND: The objectives of our study were to find out the frequency in terms of age and sex of the patients, type and site of foreign bodies, clinical manifestations and management with rigid ventilating bronchoscope. METHODS: It was a descriptive study carried out in the department of otolaryngology and head and neck surgery at Saidu Teaching Hospital swat, and was conducted from March 2005 to March 2006. A total of 42 cases collected from March 2005 to March 2006, admitted through casualty, OPD and referred by pediatric unit. All of them subjected to bronchoscopy as an emergency as well as an elective procedure. RESULTS: A total of 42 cases were included in the study. In 37 cases (88.09%) foreign bodies were removed successfully, while 4 cases (9.52%) were having no foreign body, only mucous plug was removed. One patient (2.32%) died due to cardiac arrest. PMID- 17348317 TI - Effectiveness of routine urine analysis of patient attending rural health centers in Abbottabad. AB - BACKGROUND: Renal diseases may be discovered accidentally during routine urinalysis. This study was done to see the significance of urinalysis and study the magnitude of abnormal urinalysis in patients with no symptoms of renal disease. METHODS: From 15th February to 16th March 2005, a total of 1000 samples of urine were collected from the patients attending three rural health centers of Abbottabad. Dipstick Method was used for urinalysis. RESULTS: there were 600 males and 400 female patients. The age ranged from 1 to 55 years. Proteinuria was present in 2.3%, hematuria in 4.8% patients, pyuria in 10.2% and glycosuria in 2% patients. CONCLUSION: In our setup routine urine analysis should be performed in all patients to identify the presence of unrecognized renal diseases which may benefit from simple therapeutic measures. PMID- 17348318 TI - Migrating foreign body in the thyroid gland, an unusual case. AB - We report an unusual case of an ingested foreign body in 26 year old female that perforated the esophagus and penetrated the thyroid gland. A neck exploration was done to remove the foreign body. PMID- 17348319 TI - Respiratory distress: a rare presentation of rickets. AB - Nutritional rickets has multiple presentations like skeletal deformities, tetany, hypocalcemic seizures, recurrent diarrhea, dental abnormalities, developmental delay and floppiness. Here a rare presentation of nutritional rickets is reported in five months old baby who had respiratory distress since two months and signs of respiratory distress resolved after start of vitamin-D supplementation. PMID- 17348320 TI - [3120+1kbdel8.6kb]+[p.N1303K] genotype in an Emirati cystic fibrosis patient: indication of a founder mutation in Palestinian Arabs. AB - Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disorder in Caucasian population. The disease was initially considered to be rare in Middle Eastern countries. 95% of CF in Emirati families is due to two mutations only--p.S549R(T > G) and p.F508del. We report here the case of a patient referred to CF and Respiratory Clinic at Tawam Hospital for cystic fibrosis transmembrane regulator (CFTR) gene screening to ascertain the diagnosis of CF, who was found to carry a unique genotype, signifying the importance of retrieving ancestral histories of patients with monogenic disorders. PMID- 17348321 TI - Generating political priority for safe motherhood. PMID- 17348322 TI - Abortion: thinking clearly about controversial public policy. PMID- 17348323 TI - Unmet need for sexuality education among adolescent girls in southwest Nigeria: a qualitative analysis. AB - This study utilises a qualitative approach to elicit the reproductive health concerns of girls at a Christian summer camp with a view to making recommendations on how to improve the content and process of future sessions. The girls asked questions anonymously about various aspects of their sexuality, which were analysed to identify emergent themes. There were 75 participants with ages ranging from childhood to late adolescence (7-21 years). The different levels of cognitive development are clearly illustrated in the types of questions asked. The late adolescents focused on coping with relationships and demands for sex. The early and middle adolescents focused on their feelings, relationships, menstruation and breast size. Those in childhood (7-11 years) appeared totally ignorant about parts of their body. Myths and misconceptions were identified in all age groups. Future sessions should address the peculiar needs of these different age groups. Christian and other religious groups should work with health educators to develop realistic teaching guidelines that focus on the everyday concerns of the youth. PMID- 17348324 TI - Evaluation of the ATBEF Youth Centre in Lome, Togo. AB - In 1998, the Association Togolaise Pour le Bien Etre Familiale launched a youth centre in Lome, Togo. To evaluate the centre, a three-year panel study was undertaken. Three years after being launched, about 10% of surveyed youth had visited the centre. Youth who lived close to the centre had contact with a peer educator and were exposed to television were more likely to have visited the youth centre than all others. Visiting the youth centre and having contact with a peer educator were associated with greater contraceptive use in the matched sample. Youth centre clinical users were younger, less likely to be married and less likely to have ever been pregnant than clinical users of other sites. The youth centre is meeting its goal of providing services to high-risk youth in Lome. To increase youth centre access for all youth, it will be necessary to increase the number of youth centres. PMID- 17348325 TI - Reproductive health behaviour among in-school and out-of-school youth in Kabarole District, Uganda. AB - This study was conducted to elucidate whether in-school adolescents have sexual behavioural patterns that differ from those of out-of-school adolescents. A total of 300 in-school and 256 out-of-school adolescents were interviewed. Condom use was significantly higher among in-school than out-of-school adolescents. In school adolescents had fewer sexual partners in the previous year and had started sexual activities at a later age than out-of-school adolescents. In-school adolescents were more likely to have used modern contraceptive in the past than out-of-school adolescents. We conclude that out-of-school adolescents are less likely to practice safe sex and to use modern family planning methods than in school adolescents. This indicates the need to provide more information to this group of adolescents. They are traditionally neglected in favour of in-school adolescents, who have greater access to information. PMID- 17348326 TI - Awareness of cervical cancer, Papanicolaou's smear and its utilisation among female undergraduates in Ibadan. AB - A survey was conducted among 421 undergraduates of the University of Ibadan using self-administered questionnaires probing into their risk factors for neoplastic cervical lesions, awareness of cervical cancer, Papanicolaou's smear and its utilisation. The percentage of sexually active respondents was 81.5%. Sexual exposure before the age of 20 years occurred in 51.7%. The mean age at sexual debut was 18.8 years while the modal age was 18 years. Fifty seven per cent had multiple sexual partners, but only 38.1% used condoms. Seventy one per cent were aware of cervical cancer, while only 33.5% were aware of Papanicolaou's smear. Awareness was found to be more among medical students and the married ones. On the other hand, only 8.3% of them had ever done a Papanicolaou's smear. There is a need to increase awareness and incorporate cervical screening into the pre existing university health services. Also, logistic barriers to cervical screening need to be removed. PMID- 17348327 TI - Characteristics of abortion care seekers in south-western Nigeria. AB - This prospective hospital-based study was carried out to understand the characteristics of abortion care seekers in south-western Nigeria. Information was obtained from a total of 1876 women seeking abortion at hospitals using a questionnaire. The results show that majority (60%) were between the ages of 15 and 24 years, of which adolescents between the ages of 15 and 19 years constituted 23.7%. Most (63.2%) of the respondents were unmarried, but married women also constituted a significant proportion (30.2%) of the abortion care seekers. Students were the single highest group, while the predominant economic activity was trading (26.7%). Respondents terminated their pregnancies mainly because they were students or because they did not desire to have children. Most (35.5%) of the women were introduced to providers by friends. Average contraceptive prevalence among the abortion care seekers was 27.4%. It is obvious from the results that young persons, especially in-school adolescents, should be targeted for comprehensive sexuality education especially in view of the current HIV/AIDS pandemic. PMID- 17348328 TI - Unintended pregnancy among unmarried adolescents and young women in Anambra State, south east Nigeria. AB - This study identified the characteristics and factors influencing unintended pregnancy among unmarried young women in a rural community in south-east Nigeria. One hundred and thirty six unmarried teens with unintended pregnancy attending a Christian hospital in Ozubulu, a rural community in south-east Nigeria, from January 1998 to December 2001 were included in the study. Information was obtained using a semi-structured questionnaire and in-depth interview. Over 75% of the girls had their first sexual intercourse by 19 years, and over 69% had multiple partners. Over 95% had sex for economic reasons and exchanged sex for money or gifts. Only 13.5% ever used condoms. Ninety seven per cent suffered violence such as beating and verbal abuse from family members because of the pregnancy. Most of the adolescents or young women experienced major stressors, most importantly school and job termination, partner's negative attitude, religious sanction, discrimination and stigmatisation as a result of the unintended pregnancy. Unmarried pregnant adolescents or young women have particular health and psychosocial problems. Stakeholders in adolescent health, namely, parents, teachers, religious groups and health care providers, should recognise these problems and advocate for the provision of appropriate care and youth-friendly services to help youths navigate through these problems. PMID- 17348329 TI - Community-based survey of unwanted pregnancy in southwestern Nigeria. AB - Unwanted pregnancy, and consequently unsafe abortion, remains major reproductive health problems in Nigeria that needs to be tackled. Unfortunately, there is a dearth of information on this problem at the community level. This study therefore examined the prevalence of unwanted pregnancy in the community as well as associated factors including the views, perceptions and attitudes of community members towards unwanted pregnancy and the pattern of help-seeking behaviour on unwanted pregnancy. Information was obtained from 3,743 women in urban and rural communities in two Nigerian states of Lagos and Edo. At some point in life, 26.6% of the respondents had had unwanted Pregnancy while abortion prevalence was 21.7%. Short birth intervals (21.1%), high cost of raising children (20.1%), interruption of education (20.1%) and being unmarried (17.3%) were the most common reasons for not wanting pregnancies. Most of the respondents (91.3%) were aware of some form of contraception but ever-use rate was only 36.6% while current use rate was 23.4%. Both abortion and contraceptive use were significantly associated with increasing levels of education. Unwanted pregnancy constitutes a problem even at the community level and more research is needed to understand the persistent disparity between contraceptive knowledge and usage, as increased usage will reduce unwanted pregnancy and induced abortion. PMID- 17348330 TI - An empirical investigation of attitudes towards wife-beating among men and women in seven sub-Saharan African countries. AB - This study used data from the demographic and health surveys (DHS) conducted between 1999 and 2001 in Benin, Ethiopia, Malawi, Mali, Rwanda, Uganda and Zimbabwe, to examine the magnitude and correlates of conditional acceptance of wife-beating among both men and women. Multivariate logistic regression models were fitted to investigate the independent association between different socio demographic characteristics and acceptance of wife-beating. The acceptance of wife-beating for transgressing certain gender roles was widespread in all the countries. Men were consistently less likely to justify wife-beating than women. Household wealth and education emerged as strongest and most consistent negative predictors of acceptance of wife-beating among both men and women. Older men and women were less likely to justify wife-beating. Men and women in the polygamous union were more likely to accept wife-beating, though the association was not always significant. With the exception of Uganda, women working for pay were more likely to justify wife-beating than non-working women were. The results indicate that dominant social and cultural norms create images of "ideal" women among both men and women that include definition and widespread acceptance of gender roles as well as sanction use of force to enforce these gender roles. The State and its different institutions may fail to mitigate wife-beating, as sensitivity to objectively address wife-beating may be tellingly lacking. Though education, economic growth, etc, can reduce acceptance of wife-beating, the process may be too slow and too late to make a substantial difference in the near future. Proactive measures may be required to change attitudes towards wife-beating among both men and women. PMID- 17348331 TI - Rape against women: the magnitude, perpetrators and patterns of disclosure of events in Dar es Salaam, Tanzania. AB - This cross-sectional household survey was conducted in Dar es Salaam between July and August 2000. The objectives were to establish the magnitude of rape against women, the perpetrators, disclosure of events and other related factors. Among the 1004 women who completed their interviews, 20% said they were ever raped. The known perpetrators were responsible for 92% of the most recent events. Whereas 34% of events were disclosed for non-legal purposes, only 10% were disclosed to the police. Repeated rape and patterns of disclosure were significantly associated with existing social relationships with the perpetrator. The results indicate that rape against women is a serious public health problem in Dar es Salaam commonly involving people who are close to the victims. PMID- 17348332 TI - Orofacial injuries in eclamptic Nigerians. AB - A retrospective review of one hundred and seventy three cases of eclampsia seen between 1994 and 2002 was conducted. Twenty one patients (12.1%) whose ages ranged from 18 to 35 years sustained orofacial injuries during the course of their eclamptic fits. Lacerations and bruises on the tongue, gingivae and lips accounted for injuries in all the patients. Temporomandibular joint dislocation was also recorded in one patient. Tongue lacerations were mainly due to tongue biting. Forceful insertion of objects during convulsive episodes was responsible for the bruises and deep lacerations at the ventral surface of the tongue in two patients. Two patients died from severe and uncontrolled bleeding complicated by renal failure and aspiration pneumonia from lacerations on the tongue and gingivae. Vigorous campaign should be carried out to encourage antenatal care attendance by pregnant mothers so that potential cases of eclampsia could be nipped in the bud before progressing to frank eclampsia. Furthermore, additional injuries usually inflicted on pregnant women by anxious relatives from forceful insertion of unpadded objects as mouth props should be discouraged through public health promotional campaigns. Obstetricians should be aware of the possibility of these injuries in an unconscious eclamptic patient and their life-threatening consequences if not promptly diagnosed and managed. The need to seek appropriate and early dental or maxillofacial consultation where such injuries are suspected and where services are available is imperative. PMID- 17348333 TI - Tradition and modernity in Cameroon: the confrontation between social demand and biomedical logics of health services. AB - This paper examines the cultural acceptability of biomedical obstetrical services and care across an anthropological literature review and a qualitative survey carried out in North Cameroon. The results reveal that cultural acceptability of biomedical services is impaired by a series of requirements such as a too early first prenatal visit; use in common of delivery rooms, wards and obstetrical tools; the absence of traditional healing like massage after delivery; refusal to hand over the placenta and umbilical cord to the family; and hindering the presence of family members during delivery. These evidences support a transition from normative medical system to an efficient and flexible medical system related to the expectations of the population established with its participation. This is commonly called patient-centred care. PMID- 17348334 TI - Health-seeking patterns among fatally ill Capeverdian women. AB - The circumstances of 94 deaths among females aged 15-49 years in Cape Verde were investigated to assess their access to effective care. Persons associated with the deceased women were interviewed (verbal autopsy) to explore contributing causes of death, perceived illnesses and treatment efforts. The certainty of diagnosis and avoidability of the fatal outcome were assessed by a panel ofexperts. A model of health care accessibility is elaborated to identity restricting (delay) factors. Deliberate avoidance of modern medical care and reliance on traditional medicine were major delay factors, while unawareness of the severity of symptoms and affordability limits were minor delay factors in this population. A detailed sorting of cases by health care level is used to identify the effectiveness of diagnosing, referral and care provided. Since a high proportion of avoidable deaths occurred in hospital, the quality of care may have been sub-optimal. PMID- 17348335 TI - Gynecological and related morbidities among ever-married Omani women. AB - To assess the prevalence and correlates of gynecologic and related morbidity in Omani women, a nationally representative sample of Omani women selected by a multi-stage, stratified probability sampling procedure was selected (total = 364). Questionnaire interview, physical and gynecological examination, and laboratory investigations were used to elicit information. The prevalence of lower reproductive tract infections was 22.4%, upper reproductive tract infections 2.7%, and cervical dysplasia was very rare. Genital prolapse was present in 10%, 11% had a urinary infection, 27% were anaemic, 23% were hypertensive, and 54% were either overweight or obese. The predictors of common morbidities were assessed using regression analysis according to a pre-specified conceptual model. PMID- 17348336 TI - Relation of parity to pregnancy outcome in a rural community in Zimbabwe. AB - This population-based cohort study was conducted to compare pregnancy complications and outcome among nulliparous, low (1-5) and high (> or = 6) parity women. Women who registered for antenatal care and gave birth in Guru District, Zimbabwe, between January 1995 and June 1998 were classified into groups by parity. The women were compared for baseline characteristics, utilisation of health facilities and occurrence of pregnancy complications such as hypertensive disorders of pregnancy, haemorrhage, pre-term delivery, operative delivery, low birth weight and perinatal death. In estimating risk, primiparous (parity = 1) women were used as referents. Pregnancy records for 10,569 women were analysed. Mean ages of nulliparous and high parity (> or = 6) women were 20.1 and 37.7 years respectively (p < 0.001). Prevalence of anaemia at booking (haemoglobin < or =10.5 g/dl) was reduced in nulliparous compared to multiparous women (11.7% vs 16.8%; p > or = 0.001). Nulliparous women were likely to book early (< or = 20 weeks) for antenatal care, have a higher number of visits (> or = 6) and fewer home births. Nulliparous women had higher risk for low birth weight (RR 1.70; 95% CI 1.36 - 2.13). Compared to low parity women, nulliparous and high parity women had an elevated risk of hypertensive complications RR 1.62 (95% CI 1.37-1.92) and RR 1.64 (95% CI 1.29 - 2.07) respectively. The risk of developing any pregnancy complications was highest in nulliparous women (RR 1.48; 95% 1.31- 1.67). In conclusion, nulliparous women had an increased risk of pregnancy complications. High parity women with no previous complicated pregnancy were at low risk of complications. PMID- 17348337 TI - A lighter, defter touch. Years of refinement have made laser eye surgery better than ever. PMID- 17348338 TI - Lenses for every eye. New material makes wearing contacts safer, comfier. PMID- 17348340 TI - Way beyond glasses. High-tech tools can mean independence. PMID- 17348339 TI - Getting the focus back. There's new hope for people with age-related macular degeneration. PMID- 17348341 TI - Darn those screens. PDAs, BlackBerrys--the little devices that rule our lives also play havoc with our vision. How to cope. PMID- 17348342 TI - Systematic attraction. Single hospitals faced with competitive pressures, demand for capital often look to join systems, but money may sour marriage. AB - Stand-alone hospitals often seek more security by joining a system. But those deals, like marriages, don't always work. Concerns over local control and squabbles over finances can break apart the alliances, sometimes leading to legal action. A dispute over local control led Benefis Healthcare to end its affiliation with a system. "The best thing for us to do was to part company and remain friends", says John Goodnow, left. PMID- 17348343 TI - Breaking up's hard to do. Trial to begin in Health Alliance case. PMID- 17348345 TI - Weak prospects. Federal Medicaid P4P proposal has skeptics. PMID- 17348344 TI - Medicare Advantage on hot seat. Congress presses officials on budgetary status quo. PMID- 17348346 TI - Blues gets its banking done. Consumer-driven institution opening March 1. PMID- 17348347 TI - Let the bidding begin. Another buyer interested in Sunrise Senior. PMID- 17348348 TI - Horizon Health deal hits snag. FTC launches antitrust investigation of psych pact. PMID- 17348349 TI - I see on your resume you ran CMS, gulp. CMS administrators' ethical track record questionable; it's time to buck the trend. PMID- 17348350 TI - Think you know European healthcare? Sure there's universal coverage, but more personal responsibility than you realize. PMID- 17348352 TI - Quiet giant. Blues consolidator Health Care Service Corp. may not get the same attention as for-profit WellPoint, but the company is busy making big moves. PMID- 17348351 TI - Prisoners of the system. Court rulings have led to major changes over the years in the delivery of care to the nation's inmates, a uniquely challenging patient population. PMID- 17348353 TI - By the numbers. Largest children's hospital ranked by number of staffed beds, 2005. PMID- 17348354 TI - Making the patient better--whatever the outcome. PMID- 17348355 TI - Can lifestyle choices influence breast cancer risk and prognosis? PMID- 17348356 TI - Opioid receptors in pain control. PMID- 17348357 TI - Treating cancer pain in patients addicted to drugs. PMID- 17348358 TI - Chemotherapy as palliation in advanced colon cancer. PMID- 17348360 TI - Preventing catheter-related infectious complications. PMID- 17348359 TI - Chronic GVHD still limits success with stem cell transplant. PMID- 17348361 TI - Cancer survivors: issues in symptom management. PMID- 17348362 TI - Integrative oncology: complementary therapy for cancer survivors. PMID- 17348363 TI - Updates from the 2006 Multinational Association of Supportive Care in Cancer International Symposium. PMID- 17348364 TI - Controlling symptoms in elderly lung cancer patients. PMID- 17348365 TI - Preventing emesis in lung cancer patients. PMID- 17348366 TI - Malignant bowel obstruction: individualizing treatment. PMID- 17348367 TI - Recognizing and treating depression. PMID- 17348368 TI - Managing the side effects of androgen-deprivation therapy. PMID- 17348369 TI - Bone complications: an increasing risk in patients with prostate cancer. PMID- 17348370 TI - Erectile dysfunction in patients with prostate cancer. PMID- 17348371 TI - Sexual dysfunction in men with prostate cancer: psychosocial issues. PMID- 17348372 TI - Rehabilitation after brain cancer surgery. PMID- 17348373 TI - Watch for deconditioning in cancer patients and 'prescribe' exercise. PMID- 17348374 TI - Issues in amputation. PMID- 17348375 TI - Chains weigh on on access. The FAH joins the throng offering proposals to solve the uninsured crisis, but some say their plan lacks a key element. AB - Yet another proposal for covering the uninsured landed in the news last week, as the Federation of American Hospitals offered its plan, estimated to cost 115 dollar billion annually. While the plan drew some praise, others questioned its validity. "It's hard to take seriously a proposal that doesn't even attempt to address the fundamental issue of how all is this going to get paid for," says Susan Sherry, left. PMID- 17348376 TI - What they'd gain. FAH plan could help with bad debt. PMID- 17348377 TI - CMS: spending growth slows. However, experts say GDP projections alarming. PMID- 17348378 TI - 'Nuclear' fission in Alliance trial. PMID- 17348379 TI - Trying to make it work. Zeal for pay-for-performance is ebbing. PMID- 17348380 TI - Nurses older, more plentiful, better paid: study. But critic contends lag time on data too long to be useful for policymakers. PMID- 17348381 TI - Agreement could put EHRs on fast track. Groups' compromise could lead to standard being added to CCHIT criteria by '08. PMID- 17348382 TI - Reform before coverage. Universal access in today's healthcare system is a recipe for fiscal disaster. PMID- 17348383 TI - IT goes global. Learning from what works and what doesn't--around the world. PMID- 17348384 TI - Still the matter of money. Annual IT survey shows little movement on increased budget allocations. PMID- 17348385 TI - Eyes on the EHR. Clinical systems, cost issues also among priorities. PMID- 17348386 TI - Looking for a helping hand. Despite recent federal guidance on IT subsidies for docs, not-for-profits still skittish. PMID- 17348387 TI - More moving to entry level. CPOE adoption slowly gains ground, with larger number expecting installations. PMID- 17348388 TI - The naming game. Tyco Healthcare taking on a new moniker; is it an effort to ditch the parents? PMID- 17348390 TI - [Kinetics of rearrangement of solvation sheath of an excited molecule of the fluorescent probe 4"-dimethylaminochalcone]. AB - Processes accompanying the quenching of the fluorescent probe 4" dimethylaminochalcone by hydroxyl groups of the proton-donor solvent 1-butanol have been studied. The kinetics of the deactivation of the excited state of 4" dimethylaminochalcone has been monitored from the transition absorption spectra at a time resolution of 50 fs and fluorescence decay at a time resolution of 30 ps. The data obtained allow thinking that the next picture occurs in 1-butanol. At first stage, the 4"-dimethylaminochalcone molecule in its ground state forms a hydrogen bond with an alcohol molecule. At the second stage, the absorption of light quantum and corresponding rise of the dipole moment of 4" dimethylaminochalcone take place, the initially existing hydrogen bond is retained. The third stage consists in the rearrangement of the 4" dimethylaminochalcone solvation shell formed by alcohol dipole molecules due to an increase of the dipole of moment 4"-dimethylaminochalcone; this rearrangement takes an energy of about 24 kJ/mol, the arrangement time constant is close to 40 ps; the initial hydrogen bond is retained. The fourth stage involves processes that lead to fluorescence quenching; their time constant is about 200 ps. Taking into account that the quenching is a much slower process than the relaxation of the solvation shell, it was supposed that the quenching is not a direct consequence of the solvation shell relaxation or the existence of the hydrogen bond formed prior to excitation. Then the fluorescence quenching of 4" dimethylaminochalcone can be accomplished through some other processes that are observed in other fluorescent molecules: (a) rearrangement of the initial hydrogen bond from a conformation that cannot quench the fluorescence of 4" dimethylaminochalcone to a more "effective" conformation, (b) charge transfer between the excited of molecule 4"-dimethylaminochalcone and alcohol, or (c) solvent-induced twist of the 4"-dimethylaminochalcone amino group (its withdrawal from the molecule plane) by the action of the solvent. PMID- 17348389 TI - [A comparative spin trapping study of hypobromous and hypochlorous acids interaction with tert-butyl hydroperoxide]. AB - We have demonstrated that hypochlorite (HOCI/OCl-) and hypobromite (HOBr/OBr-) can react with tert-butyl hydroperoxide with close rate constants (k(HOCl) = 10,8 M(-1) x s(1); k(HOBr) = 8,9 M(-1) x (s(-1)). By means of the spin trap 4-pyridyl 1-oxide-N-tert-butyl nitron we have found that both reactions proceed through decomposition of tert-butyl hydroperoxide and generation of tert-butyl peroxyl (OOC(CH3)3) and tert-butoxyl (OC(CH3)3) radicals, the ratio of their the concentrations being dependent on the concentration of tert-butyl hydroperoxide. Thus, hypobromite, similar to hypochlorite, is a precursor of free radicals produced in the reaction with organic hydroperoxides. This reaction can be of great importance in the intensification of free radical processes, namely, in lipid peroxidation at the stage of chain branching. PMID- 17348391 TI - [Selective labeling of barstar in a T7 polymerase system by 15N-isotopes]. AB - It has been shown that the use of a special growth medium enriched with amino acids and an inhibitor of aminotransferases alpha-aminooxyacetic acid makes possible the selectivity of labeling of barstar with 15N-leucine and 15N tryptophan. The system of selective labeling, which was previously optimized with respect to the time of introducing the label relative to the time of introducing the inductor IPTG and the inhibitor of cell polymerase rifampicin, was substantially refined by the use of the transamination inhibitor. The inhibition of aminotransferases enables one to completely eliminate the redistribution of the isotope, which is a necessary step in NMR studies even if the strongly metabolizable 15N-leucine is used. The suppression of the redistribution of the isotope by alpha-aminooxyacetic acid is a successful approach to preparation of any selectively labeled proteins in the T7 polymerase system. PMID- 17348392 TI - [Mathematical models of the oxygen-binding function of intact human hemoglobin and hemoglobin modified by UV-radiation in the presence of carbon oxide]. AB - The influence of carbon oxide and UV-radiation in doses of 151-453 J/m2 on the physiological properties of human oxyhemoglobin has been studied. Mathematical models of the oxygen-binding function of intact and modified hemoprotein have been developed. It has been found that saturation of human hemoglobin with oxygen obeys the logistic dependence. In the presence of carboxyhemoglobin, the oxygenation parameters change and saturation curves are described by the equations of degree dependence. It has been shown that UV light had the stimulating influence on the functional properties of human hemoglobin modified by carbon oxide if the concentration of carboxyform of the hemoprotein in solution was no higher than 10 per cent. The disturbance of the oxygen-binding ability of hemoglobin by the action of higher concentrations of carboxyhemoglobin was irreversible and was not corrected by UV-radiation. PMID- 17348393 TI - [Tendon fibril rotation under the influence of hydration and temperature changes]. AB - Hydration of an isolated rat tail tendon fibril induces its rotation. A similar effect is observed under the influence of temperature changes in the range of 12 38 degrees C. The direction and intensity of the rotation do not depend on the length of a tendon fibril in the range of 12-80 mm. A probabilistic character of the distribution of right- and left-rotating collagen molecules in the tendon was revealed. The direction and intensity of fibril rotation depends on the predominance of the amount of right- and left-rotating collagen molecules. The role of the rotation of collagen bundles in the mechanism of excitation of mechanoreceptors by the action of temperature is discussed. PMID- 17348394 TI - [Features of the geometry of a supercoiled DNA molecule]. AB - The features of the geometry of a supercoiled DNA molecule are considered. A model of supercoiled structure of DNA taking into account its natural helical structure has been constructed. Force factors arising in DNA has been calculated depending on winding angle. PMID- 17348395 TI - [Combined hopping-superexchange mechanism of charge transfer in DNA; a model with nearest interactions]. AB - In the framework of the earlier developed combined hopping-superexchange mechanism of charge transfer in DNA, a model with all nearest interactions between nucleobases is proposed. It is shown that the transfer rates for various types of nucleotide sequences calculated within this model are in a good agreement with experimental data. PMID- 17348396 TI - [A kinetic model of functioning and regulation of Escherichia coli isocitrate dehydrogenase]. AB - A Rapid Equilibrium Random Bi Ter mechanism of formation of two dead-end complexes was proposed to describe the experimental data on the functioning of E. coli isocitrate dehydrogenase (IDH). A kinetic model for the enzyme functioning was constructed, which assumes that it is regulated through reversible phosphorylation by its kinase/phosphatase, which in turn is regulated by IDH substrates and central metabolites such as pyruvate (Pyr), 3-phosphoglycerate (3 PG), and AMP. It was shown using the model that increasing the concentration of these effectors results in an increase of the active part of IDH, thus leading to an increase in the Krebs cycle flux. We predict that the ratio of the phosphorylated and free forms of IDH (IDHP/IDH) is more sensitive to AMP, NADPH, and isocitrate concentrations than to Pyr and 3-PG. The model allows a realistic prediction of changes in the IDHP/IDH ratio, which would occur under changes of biosynthetic and energetic loading of the E. coli cell. PMID- 17348397 TI - [On the mechanism of photoinduced electron transfer in photosystem II reaction centers]. AB - The EPR spectrum of the triplet state of photosystem II reaction centers has been studied in the case of the singly reduced primary acceptor complex QAFe2+. It was demonstrated that the shape of the spectrum does not change much when the relaxation of the primary acceptor is accelerated and when magnetic interaction between the reduced quinone molecule QA and the non-heme iron Fe2+ is disrupted. This observation confirms the earlier conclusion that the anomalous shape of the EPR spectrum is due mainly to the anisotropy of the quatum yield of the triplet state. A scheme of primary events in photosystem II is discussed, which is consistent with the observed properties of the EPR spectrum of the triplet state. PMID- 17348398 TI - [Analysis of spectral conjugation of nonuniform subantennae in the light harvesting superantenna of Oscillochloridaceae photosynthetic green bacteria]. AB - The study is concerned with the problem of optimal spectral coupling of subantennal as a strategy of effective functioning of light-harvesting antennal of photosynthesizing organisms. A theoretical analysis of the optimality of spectral coupling of currently known spectrally inhomogeneous subantennal (B750, B805-860) in the superantenna of green bacteria Oscillochloris trichoides (from the new family Oscillochloridaceal discovered by Russian researchers in 2000), performed in the study, showed that the spectral composition of subantennal is functionally nonoptimal. This made it possible to predict the occurrence of an additional subantenna (B(x)) with an intermediate energy position (750 nm < X < 805 nm) for the optimization of energy transfer along this superantenna by the functional criterion. PMID- 17348399 TI - [On the stoichiometry of intercellular Na+/K(+)-exchange]. AB - Literature data on the atomic and ionic sizes of sodium (Na+) and potassium (K+), and the thermodynamic, and physicochemical characteristics of solutions containing Na+ and K+ have been compared. It was shown that in solutions containing Na+ only the activity of H+ is 1.31 +/- 0.038 times higher than in solutions containing only K+. It was concluded that there is reason to believe that the stoichiometry of Na+/K(+)-exchange is close to 3:4. The different degree of hydratation of Na+ and K+ caused by different density of their charges is considered to be the main reason for the result obtained. PMID- 17348400 TI - [A study of the effect of low alpha-tocopherol concentrations on the dynamical parameters of microsomal membranes by the method of spin probes]. AB - The effect of alpha-tocopherol (alpha-tp) prepared in solvents of different polarity in a wide range of concentrations (10(-4) M - 10(-25) M) on lipid phase structural characteristics of microsomal membranes isolated from mouse liver cells has been investigated in vitro. Structural changes in membranes were detected on a Bruker-200D ESR-spectrometer (Germany) by the method of spin probes. Changes in the rigidity of surface lipid bilayer regions (8 A) and microviscosity of deep membrane layers (20 A) were studied using the stable nitroxyl radicals 5- and 16-doxylstearic acids, correspondingly. As a result, nonlinear multimodal dose dependences were obtained. It was demonstrated that the physiological (10(-4) M - 10(-9) M) and ultralow doses of alpha-tocopherol up to "apparent" concentrations (10(-11) M - 10(-25) M) increased the rigidity of surface lipid bilayer regions and microviscosity in the depth of membrane. Additionally, these doses of alpha-tp induced an increase in the number of thermoinduced structural transitions in deep lipid bilayer regions. The effect at "apparent" concentrations (< 10(-18) M) has only been observed in polar alpha tocopherol solutions. The results obtained are statistically reliable with a significance level of 95%. PMID- 17348401 TI - [Investigation of the effect of doxorubicin on the intracellular signaling system]. AB - The effect of the antitumor antibiotic doxorubicin on the mechanisms of intracellular signal transduction in the region of free water dispersion has been investigated by the EHF-dielectrometry method. It was shown that the drug whose main target is nuclear DNA has a rather strong influence on free cells of the nucleus, the functions of catecholamine receptors, and the complex of adenylate cyclase with the cytoskeleton. The effect of the drug has significant individual and species differences. Variants of tests for individual selection of doses in the therapeutic practice are suggested. PMID- 17348402 TI - [Kinetics of Ca2+, NADH, and oxidized flavoproteins in the frog olfactory lining under the effect of odorants]. AB - The kinetics of fluorescence of Ca(2+) - chlortertacyclin-cell membrane complex as well as of NADH and oxidized flavoproteins in receptor cells of the frog olfactory lining under the effect of odorants has been studied. Changes in the fluorescence of the olfactory lining upon stimulation by cineole and vanillin occurred more rapidly than under the effect of camphor and amyl alcohol. Differences in the kinetics of reactions of NADH and the Ca(2+)-CTC-CM complex to different odorants are apparently due to heterogeneity of molecular mechanisms associated with the involvement of different intracellular signal systems in the transduction of these odorants in the olfactory lining. In contrast to them, ammonia and beta3-mercaptoethanol penetrate into olfactory cells and inhibit the mitochondrial respiratory chain without the participation of second messengers. At the same time, the motor activity of olfactory cilia is depressed. PMID- 17348403 TI - [Spatial model of development of resistance to transgenic insecticidal crop in a pest as applied to the European corn borer]. AB - A mathematical model of the development of resistance to transgenic Bt-crop in insect-pest populations as applied to the European corn borer has been constructed. The model represents a system of differential equations in special derivatives of the reaction-diffusion type. Local interactions of three competing pest genotypes formed by the allele of Bt-resistance and allele of susceptibility, are described by the same relations as in the Kostitsyn model, and the spread of insects is modelled as diffusion. The model was used to estimate the influence of the pest on the efficiency of the "high dose-refuge" strategy, which is intended for the suppression of development of Bt-resistance in pest populations. It was shown that formal integration of the Fisher-Haldane Wright model and the diffusion term cannot adequately describe the development of Bt-resistance in a spatially heterogeneous pest population. A further development of the model is discussed. PMID- 17348404 TI - [Dynamics of the electrical activity in the form of a vortex with a straight filament in ground squirrel heart]. AB - Attacks of tachysystolia have been studied, which were induced by premature stimuli (amplitude up to 4-5 diastolic thresholds, duration 4 ms) applied after a set of rectangular impulses (amplitude 2 diastolic thresholds, duration 4 ms, frequency 0.5 or 2 Hz). The spatial and temporal distribution of electrical potential throughout the surface of a thin (approximately 1 mm) preparation was registered by two multi-electrode arrays (32 unipolar electrodes each). One array recorded the distribution of electrical potential on the endocardial surface and the other, on the epicardial one. Wave isochronous pictures (maps) corresponding to spatial and temporal propagation of excitation on the surfaces of the preparation were reconstructed on the basis of electrograms registered on each of the surfaces. On the basis of these maps, the three-dimensional structure of scroll waves, including the location, direction and velocity of the shift of filament ends as well as the shape of the thread was analyzed. The analysis of the data obtained in our experiments allow one to conclude that, under tachysystolias caused by three-dimensional scroll wave with a straight filament, there occur the following kinds of wave thread movements: (1) the wave thread may change its location from turn to turn and on the whole be located at different angles to the preparation surfaces; (2) the wave thread may precess, when one of the filament end is "secured" on the surface and the other constantly changes its location on the opposite surface; (3) the wave thread may periodically intertwine (twisted filament) and untwine; (4) dimensions of the scroll wave kernels (sections of the filament on the surfaces) may change from turn to turn both simultaneously on both surfaces (endocardial and epicardial) and on one of them only; (5) the wave thread may curve when it goes within the wall from endocardial to epicardial surfaces; the curve may come rather close the surfaces of the myocardial tissue. PMID- 17348405 TI - [Modeling of intraorgan arterial vasculatures. II. Propagation of pressure waves]. AB - The dependences of the wave conductivity of self-similar dichotomous branching models of intraorgan arterial vasculatures on the model parameters have been calculated. It was found that, with different sets of parameters, it is possible to model the sucking effect connected with negative wave reflection at the arterial branching as well as the resonant properties of arterial beds. It was shown that the selection of an adequate model for a given intraorgan vasculature should be based on the agreement between the biophysical characteristics of the model and the vasculature that reflect the propagation and reflection of pulse waves. PMID- 17348406 TI - [Protective effect of low-power laser radiation in acute toxic stress]. AB - The effect of preliminary short-term irradiation with He-Ne laser light (632.8 nm, 0.2 mW/cm2) of the thymus zone projection of male NMRI mice subjected to acute toxic stress on the responses of immune cells was studied. Stress was modeled by lipopolysaccharide injection, 250 mg/100 g of body weight, which induced a significant increase in the production of several macrophage cytokines, IL-1alpha, IL-1beta, IL-6, IL-10 and TNF-alpha. A single irradiation with laser light did not provoke considerable variations in NO production in cells but induced an enhancement in the production of heat shock proteins Hsp25, Hsp70, and Hsp90. Nevertheless, when irradiation with red laser light was applied prior to toxic stress, considerable normalization of production of nearly all cytokines studied and nitric oxide was observed. Moreover, the normalization of production of heat shock proteins has been shown in these conditions. Thus, preliminary exposure of a small area of animal skin surface provoked a significant lowering in the toxic effect of lipopolysaccharide. PMID- 17348407 TI - [Study of radioprotective effect of "Soma" preparate]. AB - Changes in the functional activity of the synthesis apparatus of rat blood lymphocytes under different scheme in application of bioadditive Soma after acute X-irradiation by fluorescent microspectrometry. Some metabolic indices in animals were investigated too. It has been shown the bioadditive Soma using in norm reliably increased the synthetic activity on days 13 and 20. Preliminary Soma using during a month followed by the same interval increased the animal radioresistance (scheme 1), while the Soma using immediately after irradiation (scheme 2) revealed no pronounced radioprotective effect. It was found the Soma increased metabolism that may be important to recover homeostasis. The results show the expediency of further investigation of the Soma radioprotective properties with different concentrations and schemes as well as the necessity of monitoring the immune system during Soma using. PMID- 17348408 TI - [A mathematical model of the development of an epidemic process with aerosol mechanism of infection]. AB - A model of a parasitical system with the respiratory transfer of pathogenic organisms is suggested. The mechanism of internal regulation and the conditions of the onset of seasonal rise of sickness are investigated. The influence of asymptomatic carriers on the formation of the virulent potential of the pathogen organism is shown. PMID- 17348409 TI - [Paranasal sinus involvement in children with central nervous system disease]. AB - BACKGROUND: Paranasal sinus involvement in the developmental age can be clinically uncharacteristic, and therefore it is commonly diagnosed accidentally with other diseases. Not all cases of such sinusitis need otolaryngologic treatment. THE AIM OF THE STUDY: Was to assess the real prevalence of sinus involvement imaging in head MR scans diagnosed in children with neurological diseases and to describe the need of laryngological therapy in these cases. MATERIAL AND METHODS: During the period of 16 months (01.2005-04.2006) 393 MR imaging was done in children hospitalized in the Department of Child Neurology, Jagiellonian University. The study was performed in 77 children with MRI changes, aged between 1,5 to 18 years old. The MR imaging (SE T1, FSET2, PD, FLAIR, IR T1, 3 and 5 mm thickness of layers in frontal, horizontal, sagittal surfaces) were performed on 1.5 T Signa Horizon HiSpeed General Electric machine. EEG, videoEEG, ophtalmologic, laryngologic, dentist's, neuropsychologic, analytic, immunologic and biochemical assessment were done. The MRI results were analyzed by otolaryngologist, and they were compared with basic neurologic diagnosis and treatment. RESULTS: Sinus involvement was diagnosed in 20% of children with neurologic diseases. In 77 children were found 125 pathologic changes, predominated (91%) by mucosal edema. In over half of the study group there were no correlation of the sinus changes and neurologic diagnosis. In 62% of children in this group none type of treatment was used, in 20% of patients the antiinflammatory therapy and in 18% the sinusotomy was proposed. CONCLUSIONS: In most of the children with neurologic diseases and with paranasal sinus involvement diagnosed in MRI, the laryngologic treatment was not necessary, however 38% cases needed it. PMID- 17348410 TI - [Preemptive analgesia in postoperative pain for children in otolaryngological department]. AB - Although much more about the safe and effective management of pain in children is now known, this knowledge has not been widely or effectively translated into routine clinical practice. Pain in children is still a big problem even thought available many possibilities to cure it. Malpractice during postoperative period influence not only for recovery, but also causes long lasting consequences (emotional changes). The most common applied method for treatment postoperative pain in children is still pharmacotherapy. One of the most effective form of it is preemptive analgesia. Specifically, preemptive analgesia may be defined as an antinociceptive treatment that prevents establishment of altered central processing of afferent input from sites of injury. The most important conditions for establishment of effective preemptive analgesia are the establishment of an effective level of antinociception before injury, and the continuation of this effective analgesic level well into the post-injury period to prevent central sensitization during the inflammatory phase. Although single-agent therapy may attenuate the central nociceptive processing, multi-modal therapy is more effective, and may be associated with fewer side effects compared with the high dose, single-agent therapy. Practical in the pediatric patients in laryngological ward seems to be one of the most effective method of pain therapy in postoperative period. Laryngological procedures in children cause a severe pain. The most common procedure in children in laryngological practice is adenotomy. There is a pressing need for further research and clinical development in the management of pain in children. PMID- 17348411 TI - [Otogenic intracranial complications from data collected at Department of Otolaryngology Collegium Medicum Jagiellonian University between 1998-2006]. AB - BACKGROUND: Otogenic intracranial complications are rare diseases. If misdiagnosed and untreated they can lead to serious condition of patient and life threatening. This group of complications ought to be kept in mind in patients with chronic otitis media. AIM OF THE STUDY: We discuss types of otogenic complications and performed treatment. MATERIAL AND METHODS: Retrospective analysis of patients treated in our department between 1998-2006 was made. About 700 ear operations were performed in that period of time. RESULTS: Intracranial otogenic complications were noticed in 9 cases. Despite performed treatment one patient with cerebellum abscess died. The rest patients were operated with good result. CONCLUSIONS: Precise otolaryngological examination with additional investigations like CT and MRI are very important to establish the final diagnosis and save patient's health or life. PMID- 17348412 TI - [Patients with chronic otitis media at the age below 16-year-old from data collected at Department of Otolaryngology Collegium Medicum Jagiellonian University between 2004-2006]. AB - BACKGROUND: Otitis media is a frequent disease in childhood. Infections of ear in children depend on differences in anatomical structure. Clinical picture of otitis media is similar in all age groups. THE AIM OF STUDY: We performed prospective analysis of patients at the age below 16-year-old treated surgically because of chronic otitis media between 2004-2006. MATERIAL AND METHODS: 250 operations of ear were performed in that period of time. We operated 28 patients below 16 year-old: 26 with chronic otitis media and 2 with otosclerosis. RESULTS: The therapy gave positive results. In 3 cases destruction of bone of skull base was noticed. Delaminations were closed during ear operation successfully. CONCLUSIONS: In children with chronic otitis media we use the same surgical procedures as in adults. We tend to make closed tympanoplasties in children. We should keep in mind possibility of asymptomatic lack of skull base bone as a consequence of chronic otitis media. PMID- 17348413 TI - [Assessment of EEG in children with partial epilepsy]. AB - INTRODUCTION: Diagnosis of the focal epilepsy is possible even based on the clinical history. More precise identification of bioelectrical focus, type of epileptic attack and type of epilepsy requires EEG or videoEEG analysis. AIM OF STUDY: The aim of the study was to assess clinical value of electro encephalography and videoelectro-encephalography in diagnostics of partial epilepsy in children. MATERIAL AND METHODS: The study group consisted of 140 children with partial epilepsy hospitalized between 1998 and 2004 in Department of Pediatric Neurology, Jagiellonian University, Krakow. The group included 70 girls and 70 boys, aged from 2 months to 17 years. 38 of the children were older than 5 years, with mean age 8 years and 4 months. The mean time of the epilepsy course was 2 years and 4 months. Children with symptomatic partial epilepsy were the biggest group and children with idiopathic partial epilepsy were in minority. More than 50% of children suffered from complex partial seizures. Statistical correlation of the EEG results and pregnancy and birth period factors, results of neurological and psychological examination was performed. All children underwent MRI and 15 HMRS neuroimaging as well. All children underwent EEG examinations and 55 children videoEEG, recording time 60 minutes for each patient. Sleep recording in 40 children, awake EEG in 93 children and both type recordings in 8 children were performed. Stroboscope, hyperventilation and sleep deprivation stimulation tests were used. All EEG recordings were assessed by 2 physicians with the EEG license and final result was a mean of their assessment. T-student test, Mann Whitney and bilateral Fisher test were used in statistical analysis. RESULTS: EEG pattern was abnormal in 139/140 children, and videoEEG in all 55 children. In the vast majority of the patients with partial epilepsy focal EEG changes were recorded (in 111/140), with a significant prevalence of unilateral changes observed in 48/111 patients. 34 children had focal EEG changes with one-site prevalence and 27/140 children had focal EEG changes in both hemispheres without any prevalence. Generalized EEG changes were revealed in 16/140 children. Hyperventilation revealed in 8 children paroxysmal bioelectric activity and in 43 enhanced abnormal EEG pattern. In all children with normal MRI imaging EEG/videoEEG methods revealed changes significant for localization of seizures onset and origin. CONCLUSIONS: (1) EEG patterns in children with partial epilepsy were dominated by localized and lateralized changes. EEG was crucial for localization of bioelectric foci especially in children with normal MRI. (2) Focal EEG changes were significantly more often in children with hippocampal sclerosis. (3) In terms of localization HMRS were more compatible with EEG than with MRI findings. HMRS examination is strongly indicated especially in children with EEG localized discharges and with normal brain MRI. PMID- 17348414 TI - [Preliminary assessment of HMRS clinical usefulness in children with partial epilepsy]. AB - INTRODUCTION: More sensitive and specific diagnostic methods in partial epilepsy in children are still searched. AIM OF STUDY: The aim of this study was to assess clinical value of magnetic resonance spectroscopy (HMRS) in diagnostics of partial epilepsy in children. The relation between HMRS data and congenital and acquired risk factors of partial epilepsy, age of onset and clinical assessment of patients were analyzed. The compatibility of HMRS, MRI and EEG/videoEEG results were assessed. MATERIALS AND METHODS: The study group consisted of 140 children with partial epilepsy hospitalized between 1998 and 2004 in Department of Pediatric Neurology, JagieIlonian University in Krakow. Different factors related to HMRS results, such as age, pregnancy and birth period factors, familiar epilepsy, patient's risk factors for appearance of epilepsy, acquired risk factors of epilepsy, results of neurological examination, type of epilepsy, status epilepticus, and signs associated with epileptic attacks were analyzed. HMRS examinations were performed by SVS PRESS technique. T-Student, Mann-Whithney and Fisher statistical tests were used. RESULTS: HMRS was performed in 16/140 children, and in 15/16 cases its results were positive. HMRS imaging was normal in 1 child with normal MRI imaging. There were no significant correlation between HMRS findings and pregnancy birth and acquired epileptogenic factors and results of neurological examination of children. Positive correlation between HMRS imaging and MRI and EEG/videoEEG results was revealed. Important diagnostic value of HMRS in partial epilepsy without changes in MRI and with localized changes in EEG was documented. CONCLUSIONS: HMRS results were more compatible with EEG/ videoEEG findings than with MR imaging. It is important to perform HMRS in children with partial epilepsy and without any MRI changes. PMID- 17348415 TI - [Laryngological presentation of patients with amyotrophic lateral sclerosis (ALS)]. AB - BACKGROUND: Not many data concerning the laryngological evaluation of Amyotrophic Lateral Sclerosis (ALS) patients exist. THE AIM OF STUDY: The profile of laryngological disturbances in patients with ALS was evaluated. MATERIAL AND METHODS: We have studied 25 ALS patients (10 with bulbar signs and 15 with limb signs only) in the standard laryngological examination. Vocal folds motion was examined fiberoscopically. RESULTS: In bulbar onset ALS cases we have showed different changes of the uni- or bilateral position of the vocal folds. In 9 out of 15 ALS patients with limb signs (without clinical bulbar signs) we also have discovered the slight disturbance of vocal folds movement or unilateral decrease of tension and mobility. CONCLUSIONS: The careful laryngological examination can shows the subtle, objective signs of the early dysfunction of vagus nerves in ALS patients before the clinical presentation of bulbar failure. PMID- 17348416 TI - [Analysis of disturbances of oesophageal phase of swallowing in patients with amyotrophic lateral sclerosis (ALS)]. AB - BACKGROUND: The occurrence of the disturbances of oropharyngeal phases of swallowing in Amyotrophic Lateral Sclerosis (ALS) patients has been well documented. THE AIM OF STUDY: Assessment of the oesophageal manometry for detection of the oesophageal phase of swallowing in ALS patients. MATERIAL AND METHODS: The study was carried out in 12 dysphagic ALS patients and 10 sex- and age- matched healthy volunteers. RESULTS: The mean upper oesophageal contractile: amplitude, duration and velocity during the wet and dry swallows in ALS individuals were statistically differ as compared to control subjects. The abnormalities of vocal folds function was also found in the fiberoscopy examination of larynx in all ALS patients. CONCLUSIONS: This study reveal the occurrence of disturbances of the oesophageal phase of swallowing in ALS patients with dysphagia. PMID- 17348417 TI - [Auditory evoked potentials in patients after acute children's lymphoblastic leukemia treatment]. AB - BACKGROUND: Acute lymphoblastic leukaemia (ALL), and especially its treatment often leads to irreversible consequences in the central and peripheral nervous system. ALL and its treatment as well, may cause disturbances of central transmission of acoustic stimuli. THE AIM: To establish, if testing of egzogenic provoked brain stem potentials can be useful for evaluation of complications of ALL treatment. The issue of analysis was the influence of past ALL and type of therapy on parameters of egzogenic potentials triggered by acoustic stimulus (BAEP) in patients after termination of treatment. RESULTS: In the group of patients treated with NY program results of middle latencies of the wave I and III were normal, however latencies of wave V and interlatencies of waves I-III, I IV and III-V were mildly elongated. Latencies and interlatencies elongated above the upper normal range were detected in 4 patients of this group: in one patient elongation of the wave V and interlatencies of waves I-IV and III-V was detected, while in the other one interlatencies of waves I-III and I-V and in the last two patients only interlatencies of waves I-III. In the group of patients treated with BFM 86/87 programs results were similar. Latencies of waves I and III were normal, while mean latencies of wave V and interlatencies of waves I-III, I-V and III-V were mildly elongated. In this group mild pathological elongation of BAEP interlatencies were detected in 5 patients. Non of them had elongation of latencies of waves I, III or V. In one patient elongated interlatencies of waves I-V and III-V were detected, in another one interlatencies of waves I-III, while in other 3 patients elongation of latencies of waves I-V. In the group of patients treated with BFM 95 program latencies of waves I, III and V were normal, while interlatencies of waves I-III, I-V and III-V were mildly elongated. In 2 patients of this group mild elongation of interlatencies of waves I-III or III-V were detected. In each patient of this group, similar as in the group BFM 86/87, latencies of waves I, III and V were normal. CONCLUSIONS: (1) BAEP abnormalities in 22.4% of patients after the treatment of childhood ALL suggest that hearing monitoring in these patients is recommended. (2) Elongation of BAEP interlatencies and latency of wave V in patients after radiation OUN therapy warrant to develop new and less toxic therapies. PMID- 17348418 TI - [Primary benign orbital tumors in experience of the Department of Otolaryngology Jagiellonian University]. AB - BACKGROUND: The important question in primary eye socket tumors surgery is total surgery and saving the patient's sight. THE AIM OF THE STUDY: It was assessment of the data of primary non malignant tumor therapy in Cracovian Department of Otolaryngology. MATERIAL AND METHODS: 145 patients (79 male and 66 female), aged 7 months-84 years, were treated in Otolaryngological Department Jagiellonian University in years 1991-2001. In 118 cases primary benign orbital tumors were removed, in remaining patients tumors were malignant. In 89 patients lateral orbitotomy by Kronlein was performed and in other cases different types of orbitotomy were used. 5 years otolaryngological and ophtalmological catamnnesis wascomplete. RESULTS: In all patients eyeball was preserved, even in 6 with optic nerve glioma. Reccurent tumors were observed in 2 cases, diplopia in 15 patients and sight's lost in 8 (in 6 with optic nerve glioma). CONCLUSIONS: In the majority of patients with radical oncological surgery it is possible to preserve eyesight. PMID- 17348419 TI - [Results of transcranial Doppler examination of cerebral blood flow in children with vertigo]. AB - BACKGROUND: Episodic recurrent vertigo in the developmental age is associated in majority of cases with disorders of the labirynth, however they can be also associated with epilepsy or migraine. Less often they are result of disorders of vertebro-basillar circulation. The important tool in the diagnosis of such disorders is Doppler examination. Transcranial Doppler (TCD) allows detection of hypoplasia or vasospasm, it helps also in evaluation of process of autoregulation and hemodynamics of circulation in the stimulation tests. AIM: The aim of our research was evaluation of circulation in carotid and vertebral arteries and transcranial examination of anterior, middle cerebral, vertebral arteries and basillar artery in children with vertigo of central origin. The reactivity of cerebral arteries in the stimulation tests: hyperventilation and upright test, was evaluated as well. MATERIAL AND METHODS: 20 children were included, aged 8-18 years (mean 14 year) with vertigo of central origin. Children with disorders of labirynth, epilepsy and migraine, as well as with vascular diseases were excluded. The control group of healthy volunteers consisted of 12 children aged 10-16 year (mean 13 year). The examination was conducted in the Lab of Neurosonography. The peak-systolic (S), end-diastolic (D) and mean velocities were measured in the carotid arteries using continuos wave, CW. Transcranial examination, TCD of the middle, anterior, vertebral and basillar arteries with the use of the pulse wave, PW was conducted with Nicolet/EME Companion III. RESULTS: Dopppler examination detected in one child with vertigo a 50% asymmetry of the velocities between vertebral arteries, with confirmed with angiography asymmetry in diameters. The basic Doppler examination did not revealed significant difference between children with vertigo and controls, as well as during hyperventilation. The upright position provoked in children with vertigo decrease of PI and RI (85% of basic value). In controls however, indexes increased 107 and 103% respectively. CONCLUSIONS: Hemodynamic changes predisposing to central vertigo in children were not detected. The stimulation in the upright test may increase the role of Doppler in the detection of hemodynamic changes. Doppler is an important tool in diagnostics of vertigo in children, allowing detection of congenital malformations of vertebro-basillar system. PMID- 17348420 TI - [Mechanisms of drug resistance in epilepsy]. AB - Epilepsy can be classified as a multifactor neurological disease which affects ca. 1% of the world's population. Approximately 30% of epileptic patients do not favourably respond to antiepileptic drug treatment, but--on the other hand--the mechanism of drug-resistance has not been satisfactorily elucidated so far. Cortical dysplasia, hippocampal sclerosis, ion channel and receptor mutations and autoimmune processes can all contribute to the development of drug-resistant epilepsy. Furthermore, a crucial role of the overexpression of ABC transporters in eliminating rapidly antiepileptic drugs from the central nervous system and, on the other hand, the insensitivity of the epileptogenic tissue to some sodium channel blockers and GABA-mimetic agents have been strongly suggested. Further progress in elucidating the molecular basis of epilepsy and a rational polytherapy with novel and classic antiepileptic drugs, along with the development of diagnostic tools, may significantly contribute to better prognostication in this disease. The present paper briefly summarizes contemporary views on drug resistance in epilepsy, being particularly concerned with its neurobiological background. PMID- 17348421 TI - [Experimental basis for the treatment of drug-resistant epilepsy]. AB - Drug-resistant epilepsy may result from an increased expression of protein transporters in the blood-brain barrier or close to an epileptic focus, negative changes in the structure of inhibitory receptors or ion channels or neurodegeneration. One of the existing therapeutic options is a combined treatment with antiepileptic drugs. It may be suggested that the selection of a proper antiepileptic drug combination should be based upon the preclinical data and first of all consider the drug combinations displaying synergy in a seizure test and antagonism or additivity in neurotoxicity tests. This condition (synergy in convulsive tests and antagonism in neurotoxicity tests) seems o be fulfilled by the following combinations: topiramate + lamotrigine, topiramate + oxcarbazepine or valproate + lamotrigine. Anticonvulsive synergy and neurotoxic additivity show: levetiracetam + carbamazepine (oxcarbazepine) or topiramate and tiagabine+gabapentin. In contrast, an evident antagonism has been found for lamotrigine + carbamazepine (or oxcarbazepine) in a seizure test. Considering experimental data from seizure and neurotoxicity tests may improve the therapy of drug-resistant epilepsy, especially that a combination of lamotrigine + carbamazepine is relatively frequently applied in epileptic patients. PMID- 17348422 TI - [Videoelectroencephalography in children with paroxysmal events]. AB - The paper presents the crucial role of video EEG, modern diagnostic method, which allowed synchronized recording of clinical status and EEG pattern of the patient. This method gives the possibility to compare these two parameters in term of paroxysmal events. Video EEG allows to diagnosed clinical events associated with bioelectrical discharges (epilepsy), recording of bioelectrical events without clinical seizures, diagnosing clinical attacks without bioelectrical discharges (pseudoseizures) and nonepileptic events (without epileptic character in video and EEG). This method is very useful especially in children and adolescents because of huge polymorphism of clinical signs, more common ambiguous diagnosis in this age and due to heterogeneity of bioelectrical brain function in children. Video EEG monitoring gives the possibility for clinical and electro-physiological interpretation of paroxysmal events and plays a crucial rule in localizing of epileptogenic focus, classification of the seizure, epilepsy type or syndrome. The role of suggestion and placebo is important in diagnosing psychogenic pseudoseizures. The duration of video EEG recording is differentiated and much more shorter in diagnosing the type of the event. Prolonged monitoring is needed in children with drag resistant epilepsy and in pre-operation evaluation. PMID- 17348423 TI - [Cranial neuropathies in children]. AB - BACKGROUND: Cranial nerves damages are very important in clinical neuropediatry. Differential diagnosis is very complicated and difficult because of variety of cranial nerves and causes of neuropathies. Functional senses disturbances, and also motor, sensory and vegetative disorders are caused by neuropathies. Paretic symptoms are commonly diagnosed, but also sometimes isolated cranial nerves pareses are seen. THE AIM OF THE STUDY: was to recall the value of differential diagnosis in cranial neuropathies for early assessment of very complicated diseases of the head and neck and for early proper therapy. METHODS: The causes of neuropathies are performed into 10 tables, others causes are described in the paper. Congenital and genetic factors of cranial neuropathies and their clinical effects are discussed. The authors described also acquired local and systemic neuropathies in the aspect of diagnostic and therapeutic possibilities. The specific signs of cranial nerves damages are also performed. CONCLUSION: Deepening of knowledge in the aspect of etiopathogenesis and clinical signs of cranial neuropathies combined with new therapeutic methods should improve the proper follow up of these disorders. PMID- 17348424 TI - [Peripheral paralysis of facial nerve in children]. AB - Peripheral facial paresis is one of the most common diagnosed neuropathies in adults and also in children. Many factors can trigger facial paresis and most frequent are infectious, carcinoma and demyelinisation diseases. Very important and interesting problem is an idiopathic facial paresis (Bell's palsy). Actually the main target of scientific research is to assess the etiology (infectious, genetic, immunologic) and to find the most appropriate treatment. PMID- 17348425 TI - [Postoperative pain therapy in otolaryngological department]. AB - The ability of the somatosensory system to detect noxious and potentially tissue damaging stimuli is an important protective mechanism, that involves multiple interacting peripheral and central mechanisms. The postoperative pain is related with surgical procedure irrevocable. The effective relief of pain is of paramount importance to anyone treating patients undergoing surgery. This should be achieved for humanitarian reasons, but there is now evidence that pain relief has significant physiological benefit. Not only does effective pain relief mean a smoother postoperative course with earlier discharge from hospital, but it may also reduce the onset of chronic pain syndromes. Pain causes an increase in the sympathetic response of the body with subsequent rises in heart rate, cardiac work and oxygen consumption. Prolonged pain can reduce physical activity and lead to venous stasis and an increased risk of deep vein thrombosis and consequent pulmonary embolism. In addition, there can be widespread effects on gut and urinary tract motility which may lead, in turn, to postoperative ileus, nausea, vomiting and urinary retention. These problems are unpleasant for the patient and may prolong hospital stay. Choice of technique will also be influenced by the degree of training and expertise of the staff. The choice of pain-relieving techniques may be influenced by the site of surgery. PMID- 17348426 TI - [Cognitive event related potentials in neuropediatrics]. AB - In the study knowledge about cognitive event related potentials, particulary P300 potential was presented. It was shown as a objective and non-invasion method of estimate of cognitive functions, allowing on estimate of memory, taking decision and degree of concentration. Their origin in state of health and many disturbances and developmental diseases of nervous system were discussed. Difficulty in their registration and interpretation in this age has shown. Endogenous evoked potentials position in neuropediatrics was discussed, especially for diagnostics of neurologic and psychiatric diseases, as well as for monitoring course and treatment of these diseases. The diagnostic value of P300 for estimate of change of cognitive function in some syndromes and development diseases as epilepsy, tumour and brain injury, headache, demyelinisation, metabolic and degeneration diseases and progressive and non progressive encephalopathies was revealed. It was reminded of requirement of practice complex research of different potentials as well as application of new stimulation methods. PMID- 17348427 TI - Cardiovascular reactivity of patients with essential and renal hypertension in an emotion-triggering interview. AB - Blood pressure reactivity to mental stress in hypertensives is much higher than in normotensives. The authors' aim in this study was to examine whether different cardiovascular responses can be induced by various stimuli in hypertensive subgroups. The authors matched 10 essential hypertensives (EHs), 10 renal hypertensives (RHs), and 10 normotensives (Ns) according to age and gender examined them during an emotion-stimulating interview, and measured blood pressure (BP) and heart rate (HR) during the phases of the interview. They observed differences in BP reactivity between EHs/RHs and Ns under some stimuli but not between EHs and RHs, as well as a marked difference in the product of systolic BP (SBP) and HR between both hypertensive groups in the anger/rage phase (p = .028) and the baseline 2 (p = .02). This shows a higher cardiovascular activation under mental stress and a lower recovery in EHs and more sensitivity to perturbation or higher central tension compared with RHs. PMID- 17348428 TI - Predictors of self-reported antidepressant adherence. AB - The authors' objectives of this research were: (1) to assess levels of selfreported antidepressant adherence and reasons for nonadherence and (2) to investigate determinants of nonadherence. A group of general hospital and community psychiatry practice mood disorder outpatients (n=80) took a self-report questionnaire that assessed beliefs about antidepressants, self-efficacy, and reasons for nonadherence. High levels of adherence were reported: 58 patients (73%) indicated they took their medication as directed more than 80% of the time. Practical issues (e.g., simply forgetting or a change in routine) were the most frequently identified reasons for nonadherence. Patients were more likely to report nonadherence if they experienced a sexual side effect, had lower self efficacy, were female, and had not completed post-secondary education. Clinicians should be cognizant of this complexity and address not only issues related to medication efficacy and tolerability, but also social mediators and health beliefs when prescribing antidepressants. PMID- 17348429 TI - Smoking cessation 3: multicomponent interventions. AB - In part 3 of this 3-part review of interventions for tobacco dependence, the authors focus on multicomponent interventions for smoking cessation. Interventions that combine behavioral and pharmacological components have been known to increase abstinence relative to a single type of therapy. Therefore, multicomponent interventions are recommended. The authors present both a brief intervention model and a multiple-session intervention model. These models can be used to create brief intensive, and quitline intervention programs and can be tailored to various types of clinicians and settings. The clinician can choose a multicomponent intervention program that is best suited to the patient's needs and preferences as well as to the clinical setting. PMID- 17348430 TI - Human affection exchange: XIV. Relational affection predicts resting heart rate and free cortisol secretion during acute stress. AB - Participants in the present study reported the amount of affectionate communication characterizing the personal relationship they currently identified as their most affectionate relationship. The authors subsequently measured their resting heart rate and baseline salivary cortisol, and then exposed participants to a series of standard laboratory stressors. The authors monitored changes in the participants' heart rates and cortisol levels during exposure to the stressors. Results indicated that levels of verbal and supportive affectionate communication in the primary relationship were inversely associated with resting heart rate and with the magnitude of free cortisol increase in response to the acute stressors. The authors discuss implications for the association between relational communication and health. PMID- 17348431 TI - Prognostic significance of adiponectin levels in non-metastatic colorectal cancer. AB - BACKGROUND: Circulating adiponectin levels are inversely correlated with the risk of colorectal cancer (CRC). This study was designed to evaluate the association between adiponectin levels and the clinicopathological variables of CRC and to analyze the possible prognostic value of adiponectin in predicting relapse-free survival. PATIENTS AND METHODS: Baseline adiponectin and serum tumor markers were analyzed in 60 patients with non-metastatic CRC followed-up from time of surgery for at least three years or until relapse. RESULTS: The median adiponectin levels were lower in CRC patients (8.3 microg/ml) than controls (13.1 microg/ml, p <0.001). Moreover, median adiponectin concentration gradually decreased with increase in tumor stage. Low pre-surgical adiponectin levels were found in 52% of the relapsing patients compared to 26% (p=0.037) of the non-relapsing patients. Logistic regression analysis demonstrated that stage of disease (OR (odds ratio)=15.9, p10 mm. Our aim was to evaluate Tc-99m sestamibi scintimammography with a hybrid (SPECTICT) device for functional anatomical mapping (FAM). PATIENTS AND METHODS: Three planar images and a chest SPECT/CT were performed with a hybrid device in 53 patients with mammographically suspicious lesions. The final histopathological diagnosis was obtained after surgery. RESULTS: The planar images were positive in 27 out of 37 carcinomas (sensitivity 73%) and the SPECT/CT in 33 (sensitivity 89.2%). The sensitivity of planar imaging and SPECT/CT was 42.9% and 71.4% in cancers < or =10 mm, and 91.3%, and 100% in cancers >10 mm, respectively. The specificity was 93.8% for both planar and SPECT/CT imaging; accuracy was 79.2% for planar scans and 90.6% for SPECT/CT. FAM was useful in providing a precise anatomical localisation of the SPECT findings. CONCLUSION: SPECT/CT scintimammography using a hybrid device is able to detect breast cancer, showing a sensitivity higher than that of planar images, especially for small cancers. PMID- 17348442 TI - The spectrum of cervical diseases induced by low-risk and undefined-risk HPVS: implications for patient management. AB - BACKGROUND: The natural history and carcinogenicity of rare and novel HPV types is unclear. MATERIALS AND METHODS: From a total of 5,964 women tested for HPV by PCR and sequence analysis, Pap smears from 293 patients harbouring mono-infection with low-risk, undetermined-risk or novel HPV genotypes were investigated. RESULTS: Sixty-three percent of patients had ASC-US, 23% LSIL, 9% were negative and 5% had HSIL in cytology. Of 30 HPV types detected, 19 were of unknown risk (UR)-types including 3 novel genotypes. Four of the UR-HPVs (HPV 69, 30, 67 and 34) could be assigned as probable high-risk types and eight as low-risk types based on phylogenetical relationship. Morphology was not discriminative with regard to HPV type, but non-classical HPV-signs were generally present even in "normal" cytologies. CONCLUSION: HPV-typing is important for risk-adapted individual patient management. Women harbouring novel high-risk or probably high risk HPVs require more intensive care than those bearing non high-risk infections. PMID- 17348443 TI - Hepatic and renal plasma cell lesions in a patient with multiple myeloma in hematological remission. AB - Plasma cell myeloma is characterized by plasma cell infiltrations, the presence of paraprotein and mostly skeletal destruction with osteolytic lesions. Liver or kidney infiltration has been described in patients with end stage multiple myeloma (MM), while the features of this malignant dissemination is not clearly understood. An atypical form of MM relapse is presented in a patient being in bone marrow remission, with simultaneous lesions in liver, kidney and suspicion of brain involvement. This case is an interesting model of refractory MM extraosseous involvement, that a clinician should be aware of when carrying out differential diagnosis. PMID- 17348444 TI - Expression of PTEN and FHIT is involved in regulating the balance between apoptosis and proliferation in lung carcinomas. AB - BACKGROUND: The lung carcinoma is a major cause of cancer-related death, but molecular aspects of its genesis and progression remain unclear. The present study aimed to clarify the roles of FHIT and PTEN expression. MATERIALS AND METHODS: Expression of FHIT and PTEN was examined using tissue microarrays (TMAs) of lung carcinoma (n = 155) and normal lung samples (n =40) by immunohistochemistry and compared with clinicopathological parameters of tumors, including expression of CPP32 and Ki-67, as well as survival time of patients. RESULTS: PTEN was positively expressed in the nuclei of stratified squamous and alveolar epithelial cells, and FHIT in the cytoplasm of stratified squamous and type II alveolar epithelial cells. Both were more frequently expressed in normal lung tissues than lung carcinomas (p<0.05). Immunohistochemically, PTEN expression gradually decreased from small cell carcinomas (SCCs), through large cell carcinomas (LCCs) and adenocarcinomas (ADs) to squamous (SQ) cell carcinomas (p <0.05), whereas FHIT was more highly expressed in ADs and LCCs, compared with SQs and SCCs (p <0.05). PTEN expression was negatively linked to lymphatic and venous invasion of tumors (p<0.05), but positively to CPP32 expression (p 70 years and assessed the prognostic significance of advanced age. PATIENTS AND METHODS: Four hundred and fifty-three patients with stage IIC-IV ovarian cancer (age>70 years n=106 [23%]), treated postoperatively with platinum based chemotherapy were retrospectively reviewed. RESULTS: Median overall survival (OS) of patients 570 years old (52.3 months, 95% CI: 43.2-61.3) was longer than that of older patients (38.8 months, 95% CI: 29.9-47.7) (p =0.005), but this difference was not significant in a multivariate analysis (p=0.978). Age >70 years was correlated with worse performance status (PS) (p=0.019), higher tumor grade (p=0.033), residual disease >2 cm (p=0.006) and less frequent paclitaxel administration (p<0.001). Toxicity from chemotherapy was similar between the two age groups, but the relative dose intensity of paclitaxel was lower among elderly patients. CONCLUSION: The worse outcome of ovarian cancer in elderly patients may be attributed to other associated adverse prognostic factors, but advanced age was not an independent prognostic factor. PMID- 17348451 TI - Significance of lymphangiogenesis as assessed by immunohistochemistry for podoplanin in patients with esophageal carcinoma. AB - BACKGROUND: Although lymph node involvement is an important prognostic factor for survival in patients with esophageal carcinoma, little is known about lymphangiogenesis in esophageal carcinoma. Podoplanin, a mutin-type transmembrane glycoprotein, specifically recognizes the lymphatic endothelium and is used as a lymphatic-specific marker. Anti-human podoplanin antibody was therefore used to quantify and evaluate the lymphangiogenesis in esophageal carcinoma. PATIENTS AND METHODS: Lymphatic endothelial cells were detected by immunohistochemistry using mouse monoclonal anti-human podoplanin antibody. The relationship between lymphatic microvessel density (LMVD) and lymphatic vessel invasion (LVI), clinicopathological factors and the prognosis in 29 patients with esophageal carcinoma was investigated. RESULTS: LMVD was significantly higher in esophageal carcinoma patients who had any of the following characteristics: T3-T4 (p=0.0370), tumors more advanced than stage III (TNM staging) (p=0.0351), lymphatic invasion (p=0.0095) and LVI (+) (p=0.0016). LVI significantly correlated with lymph node metastasis (p=0.0003), TNM staging (p=0.0182) and LMVD (p=0.0388). The survival rate of patients with a low LMVD tended to be higher than that of patients with a high LMVD (5-year survival rate, 62.5% vs. 29.4%, p=0.0832). CONCLUSION: The evaluation of lymphangiogenesis using podoplanin immunohistochemistry may be useful in predicting lymph node metastasis and the prognosis in patients with esophageal carcinoma. PMID- 17348452 TI - Relationship between chromosome 18q status and colorectal cancer prognosis: a prospective, blinded analysis of 280 patients. AB - BACKGROUND: The relationship between chromosome 18q allelic imbalance (AI) and survival in colorectal cancer (CRC) is unclear, and study design may have contributed to inconsistent results previously reported. PATIENTS AND METHODS: Two hundred and eighty tumours from CRC patients participating in a molecular sub study from a single multicentre trial of adjuvant intra-portal 5-fluorouracil were genotyped at 5 chromosome 18q microsatellite markers, blinded to clinical data and prospective to follow-up. The relationship between overall survival and AI was examined. RESULTS: Two hundred and fifty-five tumours were informative for AI. The overall rate of AI was 49%. AI was not associated with age, tumour site or size. There was no difference in five-year survival rate between patients with (60.0% SE 5.2%) and without AI (61.4% SE 5.0%), even after correcting for covariates (HR=1.17, 95%CI:0.79-1.74, p=0.4). CONCLUSION: Our data does not [corrected] support chromosome 18q AI as an important marker of survival in the adjuvant setting. It should not, therefore, be used outside clinical trials. PMID- 17348453 TI - Circulating tumour cells and survival of patients with gastric cancer. AB - BACKGROUND: The prognostic significance of the presence of tumour cells in the blood of gastric cancer patients remains unclear. Their occurrence and its association with the stage of disease and long-term survival was determined. PATIENTS AND METHODS: Fifty-seven patients with stage I-IV gastric cancer were divided into two groups: these with and these without circulating tumour cells that were identified as cytokeratin positive (CK+) cells among CD45- cells (obtained by sorting of CD45+ leukocytes). RESULTS: Tumour cells were detected prior surgery in the peripheral blood of 54.4% patients but no clear association with the stage of disease was observed. After gastrectomy detection rate was 21.1%. There was no significant difference in the 5-year survival of patients, with or without CK+ in the blood. CONCLUSION: The presence of circulating tumour cells is of no prognostic value in patients with resectable gastric cancer. PMID- 17348454 TI - A phase II trial of weekly paclitaxel and high-dose 5-fluorouracil plus leucovorin in patients with chemotherapy-pretreated metastatic breast cancer. AB - BACKGROUND: Weekly paclitaxel and infusional high-dose 5-fluorouracil/leucovorin (HDFL) are both effective regimens for metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: A study was designed using weekly paclitaxel 90 mg/m(2) 1 hour infusion followed by 2,000 mg/m(2) 5-fluorouracil plus 300 mg/m(2) leucovorin 24-hour infusion on days 1, 8 and 15, repeated every 28 days, in patients who had previously received a > or =1 regimen for MBC. The dose of paclitaxel was adjusted in each cycle according to toxicity. RESULTS: A total of 182 cycles were given to 28 patients. The doses of paclitaxel needed to be reduced only in 22 (12%) cycles. Forty-five cycles were skipped or delayed more than 7 days, mostly due to neutropenia, infection, or neurotoxicity. Twenty-five patients were evaluable for response. Four had complete response, 13 partial response, seven stable disease, and two progressive disease. The response rate was 60.7% (95% CI: 42.6-78.8). Median survival was 18.1 months (95% CI: 11.4 24.9), and progression-free survival seven months. CONCLUSION: Weekly paclitaxel plus infusional HDFL is an active and well tolerated regimen for pretreated MBC patients. PMID- 17348455 TI - Regional radiotherapy may improve outcomes in patients with early stage breast cancer undergoing breast conservation therapy. AB - BACKGROUND: Breast conservation therapy (BCT) is recommended as standard management of early breast cancer. The aim of this study was to retrospectively evaluate the results of BCT to identify prognostic factors predictive of treatment outcomes. PATIENTS AND METHODS: Four hundred and ninety-eight eligible women with unilateral stage I-II breast cancer who had undergone BCT were analyzed. RESULTS: The cumulative incidence of local recurrence (LR) was 1.9% and 3.7% at 3- and 5-years respectively. The 5-year disease-free, cancer-specific, and overall survival (DFS, CSS, OS) were 80.0%, 87.3% and 85.4% respectively. Significant independent predictors for LR included young age and absence of chemotherapy. Regional nodal radiotherapy was significantly associated with improved DFS and OS. CONCLUSION: Our results confirmed the efficacy of BCT in the treatment of early breast cancer and indicated that inclusion of regional nodal areas within the radiotherapy field might be beneficial in the BCT setting, particularly for patients with adverse risk features. PMID- 17348456 TI - Nationwide study of clinical and molecular features of hereditary non-polyposis colorectal cancer (HNPCC) in Latvia. AB - BACKGROUND: The mutational spectrum of mismatch repair (MMR) genes in the Baltic States has been reported to be quite similar to that in Poland; however during a country-wide study considerable differences in the population of Latvia were discovered. This study was undertaken to investigate the clinical and molecular features of HNPCC in Latvia. MATERIALS AND METHODS: Family cancer histories were collected, from January 2000 until October 2003, for 702 consecutive hospital based colorectal cancer (CRC) cases. In families suspected of having a history consistent with hereditary non-polyposis colorectal cancer (HNPCC), DNA testing for MLH1, MSH2 and MSH6 genes was performed. Immunohistochemical examination of the normal and the cancer tissue from large bowel tumors was undertaken for MSH2 and MSH6 protein expression in 182 out of 702 (26%) of the cases. RESULTS: Among the 702 CRC patients only 1 (0.14%) fulfilled the Amsterdam criteria. Thirteen (1.9%) cases matched the criteria for suspected HNPCC and 10 (1.4%) cases matched the late onset HNPCC criteria. Altogether in 7 out of 702 (1%) cases MMR gene mutations were detected: 2 in MLH1, 3 in MSH2 and 2 in MSH6 gene. Only one out of the seven mutations was registered in the Human Genome Mutation Database and the ICG (International Collaborational Group)-HNPCC mutation data base. Negative MSH2 and MSH6 protein expression was detected in 4 (2.2%) and 18 out of 182 (9.9%) cases respectively. CONCLUSION: The role of the classical Amsterdam criteria in diagnosing HNPCC in CRC patients from Latvia is very limited and diagnostic criteria for suspected HNPCC are the most effective. The frequency of constitutional mutations within the MMR genes is 1% of all newly diagnosed CRC cases and the spectrum of mutations is potentially characteristic. PMID- 17348457 TI - Systematic development of clinical practice guidelines for prostate biopsies: a 3 year Italian project. AB - BACKGROUND: The only available method to detect prostate cancer is prostate biopsy; however, to our knowledge, no evidence-based clinical practice guidelines have been established on this topic. MATERIALS AND METHODS: A three-year project was elaborated in which experts in the field worked to define the controversies existing in clinical practice regarding prostatic biopsies and then to develop guidelines by means of a systematic search of all the English-language literature using online databases and a consensus conference. RESULTS AND CONCLUSION: The guidelines were formulated to help practitioners in making clinical decisions regarding the appropriate time the patient should undergo prostate biopsy, the type of antibiotic prophylaxis and anaesthesia, the biopsy approach, the method for processing and reporting prostatic needle cores, the biopsy technique, when to repeat a biopsy after a prior negative biopsy, radiotherapy or radical prostatectomy and the accuracy of biopsies in staging prostate cancer. PMID- 17348458 TI - Phase II study of regional chemotherapy using the hypoxic abdominal perfusion technique in advanced abdominal carcinoma. 5-FU pharmacokinetics, complications and outcome. AB - The aim of this study was to verify the rationale of a hypoxic abdominal perfusion (HAP) technique for the perfusion of 5-FU, mitomycin C and cisplatin in patients with inoperable, recurrent abdominal cancer. PATIENTS AND METHODS: In a phase II study, 59 patients with various non-resectable abdominal tumours were treated with 102 perfusions by the HAP-technique. The HAP-technique was performed by using double-balloon arterial-venous catheters that selectively isolated the abdominal vascular section and perfusion was provided by an extracorporal pump for 20 min. Thirty-four patients with unresectable colorectal cancer, 11 with unresectable gastric cancer, eight with unresectable pancreatic cancer and six with cancer of the gall bladder were included. They were treated with a combination of 5-fluorouracil (5-FU 1 g/m(2)), mitomycin C (MMC, 10 mg/m(2)) plus cisplatin (50 mg/m(2)) infused into the isolated abdominal compartment. The cytostatic concentration of 5-FU was determined intrainterventionally within the systemic and regional compartment. Toxicity- and procedure-related complications were documented. Tumour responses were assessed by computer tomography. RESULTS: 5-FU concentration was 16.3-fold higher within the regional compared to the systemic compartment at its maximum, and the area under the curve (AUC) was 7.9 times larger. During the procedure two major complications were experienced (1x perforation of the A. iliaca, lx deep vein thrombosis), no deaths occurred during surgery or in the postoperative period. Minimal systemic and local toxicities were observed (WHO grade III-IV 1%, grade I-II 33%). No complete response but 22 partial responses were observed. Median survival was 15.5 months for colorectal cancer, 12. 5 months for gastric cancer, 12.7 months for pancreatic cancer and 7.8 months for gall bladder cancer. CONCLUSION: The hypoxic abdominal perfusion is a safe and effective palliative treatment for patients with unresectable advanced colorectal, gastric and pancreatic carcinoma. The HAP has not shown promising results for advanced gall bladder cancer. These encouraging clinical results require further evaluation. PMID- 17348459 TI - Low-dose chemotherapy with leucovorin plus 5-fluorouracil for colorectal cancer can maintain host immunity. AB - BACKGROUND: Anticancer drugs may frequently show host immunosuppression. Low-dose chemotherapy has been used for unresectable cancer as a tumor dormancy therapy, and it has been reported that the patients treated this way demonstrated favorable survival without toxicity. In this study, host immunity before and after a low-dose leucovorin plus 5-fluorouracil regimen (low-dose LV/5-FU) and S 1 plus irinotecan regimen (S-1/CPT-11) was compared to assess whether low-dose chemotherapy can maintain host immunity. PATIENTS AND METHODS: Fourteen patients with recurrent or metastatic colorectal cancer underwent low-dose LV/5-FU, or S 1/CPT-11 treatment. The host immunity (cytokine production of the peripheral blood mono-nuclear cells (PBMC), serum soluble interleukin-2 receptor (sIL-2R) levels and phenotypic analyses of the PBMC) was measured before and after the first chemotherapy treatment. RESULTS: An increase of sIL-2R and CD4+CD25+ T cells with S-1/CPT-11 treatment, and a decrease with low-dose LV/5-FU treatment were observed and these changes in the first course were significantly different (p =0.0722 for the slL-2R, p=0. 0187for the CD4+CD25+ T cells). CONCLUSION: The current study indicated that there is no change or an improvement in host immunity with the low-dose LV/5-FU treatment as compared with the S-1/CPT-11 treatment. Low-dose LV/5-FU treatment should be considered for metastatic colorectal cancer in order to maintain a host immunity during chemotherapy. PMID- 17348460 TI - A phase III randomized study comparing paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer. AB - AIM: To assess progression-free survival (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer receiving the combination of cisplatin (75 mg/m(2) i.v.) and cyclophosphamide (700 mg/m(2) i.v.) (CP), or the combination of paclitaxel (175 mg/m2) followed by cisplatin (75 mg/m2) (TP). PATIENTS AND METHODS: One hundred and twenty patients were randomized to receive six cycles of one of the treatments every 3 weeks. If measurable, complete response (CR) or partial response (PR) was determined. RESULTS: There was a significant difference (p<0.05) in the frequency of response (CR +PR) rates between treatment groups, in favor of paclitaxel containing regimen. The median PFS was 9 months for patients in the CP group and 12 months for patients in the TP group (log-rank p=0.215). The median OS were 24 months and 20 months in TP and CP arms, respectively (log-rank p=0.350). Neutropenia and alopecia were more severe with paclitaxel-containing regimen. CONCLUSION: Although OS and PFS were similar in two arms, TP regimen yielded superior response rates relative to CP, with an acceptable toxicity profile. Therefore, the TP regimen remains the preferred initial treatment option. PMID- 17348461 TI - MRI spectroscopy in screening of prostate cancer. AB - BACKGROUND: The purpose of this study was to evaluate the suitability of MR Spectroscopy in screening for prostate cancer in comparison to T2-weighted MR imaging. MATERIALS AND METHODS: Forty-six patients with biopsy confirmed prostate cancer underwent combined endorectal-body-phased-array MRI at 1.5T (Tesla). Twelve patients were additionally examined with 3D-spectroscopy sequence. The results of the spectroscopy were compared with the findings of T2-weighted MR imaging and the histological examination of radical prostatectomy specimens. RESULTS: With 3D-spectroscopy, a choline+creatine/citrate-ratio of 0.45 for healthy tissue and a ratio of 1.90 for tumor tissue were found and a significant difference between the groups was demonstrated. In 6 cases diagnosis of tumor localization was improved with spectroscopy in comparison with T2-weighted imaging alone. CONCLUSION: 3D-spectroscopy is a suitable technique for improving MR imaging of prostate cancer. This method can improve the diagnostic accuracy of T2-weighted imaging alone. At present, 3D-CSI spectroscopy alone can not be recommended with sufficient validity. PMID- 17348462 TI - [Binocular vision and vertical strabismus]. AB - BACKGROUND/AIM: Elevation in adduction is the most common pattern of vertical strabismus, and it is mostly treated with surgery. The results of weaking of inferior oblique muscle are very changeable. The aim of this study was to evaluate binocular vision using sensory tests before and one and six months after the surgery. METHODS: A total of 79 children were divided in two groups: the first, with inferior oblique muscle of overaction (n = 52), and the second with dissociated vertical deviation (DVD), and primary inferior oblique muscle overaction (n = 27). We tested them by polaroid mirror test (PMT), Worth test at distance and near, fusion amplitudes on sinoptofore, Lang I stereo test and Wirt Titmus stereo test. We examined our patients before and two times after the surgery for vertical strabismus. RESULT: Foveal suppression in the group I was found in 60.5% of the patients before, and in 56.4% after the surgery. In group II Foveal suppression was detected in 64.7% of the patients before, but in 55.6% 6 months after the surgery with PMT. Worth test revealed suppression in 23.5% of the patients before, and in 40.7% after the vertical muscle surgery. Parafoveal fussion persisted in about 1/3 of the patients before the surgery, and their amplitudes were a little largen after the surgery in the group I patients. Lang I stereo test was negative in 53.9% before and 51.9% after the surgery in the group I, and in 48.2% of the patients before and after the surgery in the group II patients. Wirt-Titmus stereo test was negative in 74.5% of the patients before and in 72.9% after the surgery in the group I, but in the group II it was negative in 70.8% before and in 68.0% of the patients 6 months after the surgery. CONCLUSION: Binocular responses were found after surgury in 65.7% of the patients the group I and in 55.6% patients the group II. There was no significant difference between these two groups, but binocular responses were more often in the patients of the group I. PMID- 17348463 TI - [Influence of the double antiplatelet therapy on patency of the occluded artery after acute myocardial infarction with ST-segment elevation]. AB - BACKGROUND/AIM: Most patients with acute myocardial infarction with ST-segment elevation (STEMI) are still treated with pharmacological reperfusion, which is not always successful. That is the reason for searching possibilities for a better success of reperfusion with adding new antiplatelet drugs. The aim of this study was to investigate weather addition of clopidogrel as a second antiplatelet drug, improves the patency of the infarct-related artery after STEMI. METHODS: We prospectively enrolled 65 patients, 29-72 years old, hospitalized due to the first STEMI within 6 hours after the on-set of a chest pain. They were treated with a fibrinolytic agent (streptokinase or tissue plasminogen activator--tPA), aspirin, and low molecular heparin (enoxaparin). A group of 50 patients, beside this therapy, received clopidogrel. Coronary angiography was performed between 5th and 10th day of hospitalization to assess for late patency of the infarct related artery. Infarct-related artery was considered as patent if thrombolysis in myocardial infarction (TIMI) flow grade was 2 or 3, and as occluded if TIMI flow grade was 0 or 1. RESULTS: In the group of patients who received double antiplatelet therapy (aspirin and clopidogrel), infarct-related artery was occluded in 3 cases (6%); in the group of patients without clopidogrel, infarct related artery was occluded in 4 patients (26.7%),p < 0.05. There were less frequency of postinfarction angina (6% vs 13.3%), and rarer necessity for rescue percutaneous coronary intervention (4% vs. 13.3%) in the first group, but without statistical significance. CONCLUSION: Adding of clopidogrel to the standard reperfusion pharmacotherapy, as a second antiplatelet drug, increases the number of patients with patent infarct-related artery and the success of reperfusion. PMID- 17348464 TI - Damage of tubule cells in diabetic nephropathy type 2: urinary N-acetyl-beta-D glucosaminidasis and gamma-glutamil-transferasis. AB - BACKGROUND/AIM: A damage of tubular epithelial cells is followed by the release of cell enzymes and production of proinflammatory compounds, which lead to the tubulointerstitial damage. The aim of this study was to examine the function of renal tubules in the patients with diabetes mellitus type 2 (DM type 2) and the various proteinuria degrees, to establish the damage of the proximal tubule cells caused by DM type 2 by determining urinary N-acetyl-beta-D-glucosaminidasis (beta NAG) and gamma-glutamil-transferasis (gamma-GT) activity in urine, as well as to compare the obtained results in the examined groups of patients with the values in the healthy examinees. METHODS: A complete examination of renal function and selective enzymuria was performed in 37 patients with DM type 2, and 14 healthy examinees as the controls. The patients were divided in three groups according to the degree of proteinuria. The first group consisted of the patients with diabetes without microalbuminuria; the second one consisted of the patients with proteinuria of < 300 mg/24 h, and microalbuminuria of > 20 mg/24 h, while the third one included the patients with proteinuria of > 300 mg/24 h. RESULTS: In the patients with DM type 2 and the preserved global renal function, fractional excretion of sodium, potassium and phosphates, as well as renal threshold of phosphates concentration, were not sensitive parameters for discovering the damage of the renal tubule function. The determination of beta-NAG activity proved to be the most sensitive parameter for early discovering of tubule cells damages. The difference among the examined groups was statistically highly significant. CONCLUSION: The increased presence of beta-NAG in the urine of DM type 2 patients, pointed out an early tubular disorder and damage of cells, while gamma-GT was a less sensitive indicator of this damage. PMID- 17348465 TI - [Restless legs syndrome prevalence in patients on chronic hemodialysis in central Serbia]. AB - BACKGROUND/AIM: Restless legs syndrome (RLS) is a sensorymotor disorder and the core feature of this syndrome is a distressing, irresistible need or urge to move the legs. RLS is one of the most troublesome conditions experienced by endstage renal disease patients treated with regular hemodialysis, and is significantly associated with their increased mortality. The aim of this study was to assess the prevalence of RLS in the patients with end-stage renal failure in the three dialysis centers in central Serbia, and to investigate the association of the syndrome with clinical characteristics and biochemical variables. METHODS: A cross-sectional multicentric study in which 166 consecutive hemodialysis patients were evaluated using a standard questionnaire based on diagnostic criteria elaborated by the International Restless Legs Syndrome Study Group was performed. All patients were reinterviewed and clinically examined by a qualified neurologist. The data on the patients with and without RLS were compared. RESULTS: The prevalence of RLS was 22.96% (95% CI, 16.57% to 29.35%). There was no significant difference in duration of hemodialysis and clinical characteristics when we compared the patients with RLS with those without RLS. We found significantly higher levels of blood urea nitrogen and creatinine and lower level of Kt/V index in the patients with RLS, which might point to inadequate dialysis in these patients. CONCLUSION: In our study the prevalence of RLS in the patients on the regular hemodialysis was 22.96%. The obtained results are similar to those of other studies using the same methodology in the white population on the regular hemodialysis. PMID- 17348466 TI - Limb salvage procedure in occlusion of the infrapopliteal arteries. AB - BACKGROUND/AIM: Limb salvage is a procedure for treatment of the causes of ischemia in the peripheral arteries of the lower limbs. This procedure consists of percutaneous transluminal angioplasty (PTA) of arteries of the infrapopliteal segment in the lower limbs, endovascular stents implantation and selective intraarterial thrombolytic therapy. The main PTA principle is balloon dilatation of a blood vessel and increasing blood flow in this zone. The aim of this study was to show the validity and benefits of applying this procedure in pathologically corrupted arteries of the infrapopliteal segment. METHODS: A prospective study included 30 patients: 15 with PTA dilatations, 13 with stents implantations and five with thrombolytic therapy. The follow-up pertiod was: immediately after the procedure, a month later, and six months later. RESULTS: Of the 15 patients with balloon dilatation, three still suffered from artery stenosis, and they additionally underwent stents implantation. These three patients were in the group of 13 patients who had underwent stent implantation. The last group consisted of five patients with thrombolytic therapy (urokinase, streptokinase, rt-PA--recombinant tissue plasminogen activator). Restenosis appeared only in the three patients from the first group (PTA) immediately after the intervention. A month later, there was no restenosis or ischemia of the limbs. After six months, restenosis appeared in three patients from the first group (PTA), in one patient from the second group (stent), and in two patients from the third group (thrombolytic therapy). The best results were shown by the stent implantation method (successful in 92.3% of the cases), PTA (75%), and thrombolytic therapy (60%). CONCLUSION: On the basis of the obtained results it can be concluded that the limb salvage method in case of occluded arteries of infrapopliteal segment is fully justified, especially the stent implantation method being successful in 92.3% of the patients within a six month-period of time, which is a relevant proof of its efficiency. PMID- 17348467 TI - [Amblyopia screening]. PMID- 17348468 TI - [Pathophysiology of the lung inhalation injuries]. PMID- 17348469 TI - [Recombinant factor VII (NovoSeven) in intraoperative blood saving during neurosurgical treatment of the brain arteriovenous malformation]. AB - BACKGROUND: Cerebral arteriovenous (AV) malformation causes, due to the increased blood flow through a malformation, a massive intraoperative bleeding complicating, so, surgical treatment. The use of intraoperative blood saving apparatus during surgery and a recombinant factor VII-a (NovoSeven) significantly reduce complications during surgical treatment. CASE REPORT: We reported a case of surgical treatment of the patient with AV malformation of IV stage according to the Spetzler-Martin scale, in the brain. Due to a possible heavy bleeding we used a apparatus for intrasurgical blood recovery, Cell Saver, Sequestra 1 000, Medtronic, U.S.A., and recombinant human factor VIIa (rFVIIa--NovoSeven, NovoNordisk, Denmark) to control bleeding and restore an adequate hemostasis. CONCLUSION: The use of an apparatus for intraoperative blood saving, as well as the NovoSeven preparation in the management of AV malformation of IV stage, showed to be successful. PMID- 17348470 TI - [Angiectatic pseudocyst of the pancreatic head]. AB - BACKGROUND: Arteriovenous malformations of the pancreas are very rare, most frequently congenital ones, but tending to increase frequency, predominantly due to the introduction and use of new diagnostic modalities. They usually present with gastrointestinal bleeding and abdominal pain. CASE REPORT: The autors presented a 52-year-old woman in whom, during the investigation for the abdominal pain and gastrointestinal bleeding, an ultrasonography showed a hypoechogenic lesion within the head of the pancreas 3 cm in diameter. Endoscopic ultrasound showed an irregular hypoechogenic lesion. Computed tomography showed a low density area within the lesion (< 10HU). At endoscopic retrograde cholangiopancreatography, a cystic lesion within the head of the pancreas was filled with contrast from the normal pancreatic duct. Angiography showed an arteriovenous malformation within the head of the pancreas. The patient underwent pylorus preserving cephalic duodenopancreatectomy. The diagnosis of arteriovenous malformation, probably of congenital origin, was confirmed on histology. CONCLUSION: Arteriovenous malformations should be considered in patients with gastrointestinal bleeding of unknown etiology. In this case, the lesion was taken into account preoperatively, based on color Doppler ultrasonography and angiography. The best results of treatment can be achieved with resection, but it has to be performed before an eventual portal hypertension takes place. PMID- 17348471 TI - [Nasopalatine duct cyst]. AB - BACKGROUND: Nasopalatine duct cyst is a developmental, nonodontogenic cyst of jaw. CASE REPORT: We presented a 46-year-old male with nasopalatine duct cyst. The clinical examination revealed fluctuant swellings of the anterior palate, without pain, 4-5 cm in diametar. Both radiographs showed the presence of an ovoid radiolucency located in the midline of the maxilla between the roots of central maxillary incisor teeth with peripheral sclerosis, 25 x 35 cm in diametar. Surgical treatment was performed under local anaesthesia (Articainchloridum 4% - 3M ESPE) using a palatine approach. Postoperatively, no paresthesia of the anterior palate in inervation area of nasopalatine nerve was registrated. Pathohistologic findings proved both clinical and radiological diagnosis. CONCLUSION: Nasopalatine duct cyst is a rare lesion which slowly develops. The diagnosis is mainly based on radiography, tooth vitality testing and histologic findings. After a correctly applied clinical diagnosis procedure and surgicel treatment, recurrence is rare. PMID- 17348472 TI - [Giants of war surgery--Part 2]. PMID- 17348473 TI - Rembrandt--aging and sickness: a combined look by plastic surgeons, an art researcher and an internal medicine specialist. AB - Rembrandt van Rijn (1606-1669) left behind the largest collection of self portraits in the history of art. These portraits were painted over a period of 41 years, using a realistic technique. To evaluate Rembrandt's aging process we studied 25 uncontested Rembrandt oil self-portraits by means of objective and descriptive techniques. By measuring brow position changes through the years, we demonstrated that brow descent started in the second half of the third decade and began to level out in the fourth decade. Based on Rembrandts' aging physiognomy, from age 22 to 63, we believe that Rembrandt did not suffer from temporal arteritis, hypothyroidism, rosacea, or rhynophima and that no other facial signs of systemic diseases are evident, contrary to the opinions expressed by other medical professionals. We suggest that Rembrandt suffered from melancholia or mild depression, and propose the possibility of chronic lead poisoning as a theoretical illness that he might have had. PMID- 17348474 TI - Ultrasound-guided foam sclerotherapy in patients with Klippel-Trenaunay syndrome. AB - BACKGROUND: Klippel-Trenaunay syndrome, a congenital disorder, is characterized by capillary malformation, varicosities and bony or soft tissue hypertrophy. Since there is no cure for this disorder, treatment is directed towards secondary prevention of venous hypertension and preservation of functional integrity of the legs. Elastic stockings are the mainstay of treatment and are indicated in all cases. Surgery is reserved only for a few selected symptomatic patients, however the outcome is unsatisfactory in most cases, with recurrent pain, edema, poor cosmetic result and limb deformity. Ultrasound-guided foam sclerotherapy is a recently introduced minimally invasive ambulatory procedure for the treatment of chronic venous insufficiency. It was recently introduced to treat this disorder. OBJECTIVES: To evaluate the efficacy of USFS in the treatment of patients with Klippel-Trenaunay syndrome. METHODS: Seven patients diagnosed with Klippel Trenaunay, with massive lower extremity involvement, were treated with USFS between October 2003 and October 2005. Sclerovein (polidocanol, Resinag, Switzerland) 2-4% was used as the sclerosant. The signs, symptoms and overall patient satisfaction were assessed before, during and after the treatment. RESULTS: Patients' mean age was 26 years (range 15-54). The CEAP clinical classification, with ascending severity ranging from 0 (no signs) to 6 (active venous ulcer), was C4 in five patients (71.5%) and C5 and C6 in one patient each. The average number of sessions was 14.5 (range 9-21). No major complications were encountered. All seven patients reported improvement in signs and symptoms. Five of the 7 patients (71%) were very satisfied with the cosmetic result. CONCLUSION: USFS is an effective minimally invasive ambulatory technique, essentially pain free and with excellent short-term results in patients with Klippel-Trenaunay syndrome (when the deep system is functional). Long-term results and larger study groups are warranted. PMID- 17348475 TI - Leptin and C-reactive protein levels correlate during minor infection in children. AB - BACKGROUND: Leptin, a pleiotropic hormone, has been suggested to be part of an acute-phase response during an inflammatory stimulus. Its correlation with other acute-phase reactants during minor infection in children has not been investigated. OBJECTIVES: To study the correlation between levels of serum leptin and those of C-reactive protein, a well-documented acute-phase reactant, in a series of pediatric patients with acute minor infections. METHODS: Leptin and CRP levels were measured in 62 blood samples of pediatric patients presenting with mild febrile illness who were admitted to Dana Children's Hospital in Israel. All children were finally diagnosed as having minor infection based on the negative blood/urine cultures and favorable outcome. RESULTS: Serum leptin level was positively correlated with CRP (r2 = 0.5), total white blood cells (r2 = 0.33) and absolute neutrophil count (r2 = 0.31). The regression coefficient was the highest between leptin and CRP. CONCLUSIONS: Circulating leptin concentrations are positively correlated with CRP levels during acute minor infection in children visiting the emergency room for febrile illnesses. Our observation suggests that leptin is indeed a part of acute-phase proteins. The wide scattering showed that it is not a better marker in minor infections than CRP, but it may contribute to weight loss and anorexia seen in a minority of patients during mild infections. PMID- 17348476 TI - Drug-induced thyrotoxicosis: the surgical option. AB - BACKGROUND: Drug-induced thyrotoxicosis is not uncommon. It may worsen life threatening arrhythmias and may be refractory to medical treatment. Near-total thyroidectomy presents a valid alternative to medical therapy and should be considered early in the management of the disease. OBJECTIVES: To assess whether near-total thyroidectomy was a viable approach for our patients. METHODS: Twelve patients--7 men and 5 women, aged 63 to 82 years--presented with drug-induced fulminant thyrotoxicosis following 1 to 12 months of amiodarone treatment (11 patients, mean 7 months) and after a 6 months course of interferon-alpha treatment (one patient). Medical therapy included propylthiouracil in doses up to 1200 mg/day in all patients and a beta-receptor antagonist in seven. Five patients had to stop amiodarone treatment and start high doses of steroids. A thyroid scan was performed in all patients using 5 mCi of Tc-99m pertechnetate. The thyroid scan showed absent uptake of the tracer in the thyroid bed in all patients, precluding the use of radioablation. RESULTS: Four patients (three with AIT and one with interferon therapy) who did not respond to 3 months of medical therapy required surgical thyroidectomy due to severe unremitting thyrotoxicosis. A near-total thyroidectomy resulted in rapid correction of thyrotoxicosis, enabling continuation of the anti-arrhythmic drug. There were no intraoperative or postoperative arrhythmias. Subsequently, all patients recovered rapidly and remained well and euthyroid on thyroxine replacement therapy. CONCLUSIONS: Since surgery results in rapid control of thyrotoxicosis and permits continued therapy with amiodarone, we suggest that near-total thyroidectomy warrants consideration as a definitive treatment for resistant amiodarone or interferon-induced thyrotoxicosis. PMID- 17348477 TI - Percutaneous Achilles tendon repair combined with real-time sonography. AB - BACKGROUND: When encountering complaints of pain in the area of Achilles tendon with a suspected lesion, the clinician seldom reaches a precise diagnosis based only on X-ray and clinical examination. Ultrasonography is useful for evaluating the pathology and treatment. OBJECTIVES: To assess the relative contribution of real-time intraoperative ultrasound examination and immediate postoperative ultrasound in patients with acute rupture of the Achilles tendon treated by percutaneous suture method. The combination of both procedures provides a unique advantage that could facilitate better results. METHODS: Ultrasound examination was used in 20 patients with acute rupture of the Achilles tendon who were treated surgically. Intraoperative as well as postoperative ultrasound examinations were performed in 5 patients while 15 patients underwent an immediate postoperative ultrasound. RESULTS: Ultrasound pathologies were found in all patients. Percutaneous surgical correction of ruptured Achilles tendon with accurate positioning of the foot using real-time sonography was successful in all the patients. CONCLUSION: As in many other soft tissue lesions, ultrasonography is a useful tool for evaluating the pathology and for planning the surgical correction of ruptures in the Achilles tendon. PMID- 17348478 TI - Association between maternal and adult offspring utilization of primary healthcare. AB - BACKGROUND: Healthcare behavior occurs within the context of the family unit. Little research has investigated the influences among adult family members regarding their use of medical care services. OBJECTIVES: To investigate the effects of maternal attendance patterns and maternal self-assessed health status on those of adult children. METHODS: This study was a retrospective cohort, analyzing both patient records for physician visits and mailed self-administered questionnaires regarding subjective health assessment. We evaluated a unique study group of multi-generational families with free and equal access to medical services at a primary care kibbutz clinic in Israel. This enabled an exclusive focus on the association between the use of healthcare by mothers and their grown children. RESULTS: Controlling for the subjects' age, gender and number of chronic diagnoses, a significant association exists between the family physician visit rates of a mother and those of her grown offspring (P = 0.03). Low self health assessment is associated with higher levels of physician utilization (P = 0.003). Maternal self-health evaluation is associated with her adult children's own self-health evaluation (odds ratio 5.9, P = 0.04) and their rates of physician utilization (one additional offspring visit per year for low maternal self-health, P = 0.02). CONCLUSIONS: A mother's behavior patterns measured via self-rated health status and physician visit rates serve as a proxy for maternal attitudes regarding healthcare, and these attitudes are possibly imparted to her children for life. This study provides unique evidence for a maternal health behavior effect on grown children, and enables a more complete understanding of families attending the primary care clinic. PMID- 17348480 TI - Transplantation of newborn lacrimal gland cells in a rat model of reduced tear secretion. AB - BACKGROUND: Decreased lacrimal gland output may cause dry eye syndrome. Using a rat model, we examined the feasibility of transplanting lacrimal gland cells from newborns. OBJECTIVES: To restore lacrimal gland function in eyes with compromised tear production. METHODS: A model of dry eye in adult rats was developed by unilateral surgical removal of the main lacrimal gland. Tear secretion in both eyes was then assessed by masked Schirmer's test. Lacrimal gland tissue from newborn rats was transplanted into the fibrous connective tissue in which the lacrimal gland had been embedded. Masked Schirmer's test was repeated 4, 8 and 12 weeks after transplantation. RESULTS: Schirmer's test performed in 13 rats 10 days after unilateral lacrimal gland excision revealed significantly less wetting on the side with excised gland compared with the normal side (P < 0.003). The lack of secreting cells on the operated side was verified histologically. The reduction in tear secretion on the operated side remained significant for 8 weeks on average. In the six rats with transplanted lacrimal gland tissue however, there were no differences in tear reduction between the two eyes at 4, 8 or 12 weeks after the operation (P = 0.81, 0.56 and 0.8, respectively). CONCLUSIONS: Transplantation of lacrimal gland tissue from newborn rats effectively restored eye wetting in this new model. Further research is needed to evaluate this new approach for treating lacrimal gland dysfunction. Using this model might also facilitate evaluation of potential clinical treatments for dry eyes. PMID- 17348479 TI - Differences between soldiers, with and without emotional distress, in number of primary care medical visits and type of presenting complaints. AB - BACKGROUND: In 2003 a total of 43 soldiers in the Israel Defense Forces committed suicide; only 20% of them were known to the IDF mental health services. Somatic symptoms are often the only presentation of emotional distress during the primary care visit and may be the key to early identification and treatment. OBJECTIVES: To examine whether the information in the medical records of soldiers can be used to identify those suffering from anxiety, affective or somatoform disorder. METHODS: We conducted a case-control study using the information in the electronic medical records of soldiers who during their 3 year service developed affective disorder, anxiety, or somatoform disorder. A control group was matched for recruitment date, type of unit and occupation in the service, and the Performance Prediction Score. The number and reasons for physician visits were collated. RESULTS: The files of 285 soldiers were examined: 155 cases and 130 controls. The numbers of visits (mean +/- SD) during the 3 and 6 month periods in the case and control groups were 4.7 +/- 3.3 and 7.1 +/- 5.0, and 4.1 +/- 2.9 and 5.9 +/- 4.6 respectively. The difference was statistically significant only for the 6 month period (P < 0.05). The variables that remained significant, after stepwise multivariate regression were the Performance Prediction Score and the presenting complaints of back pain and diarrhea. CONCLUSIONS: These findings may spur the development of a computer-generated warning for the primary care physician who will then be able to interview his or her patient appropriately and identify mental distress earlier. PMID- 17348481 TI - Critical validation of ultrasound Doppler in the diagnosis of torsion of undescended testis. AB - BACKGROUND: Testicular torsion associated with undescended testis is uncommon but requires immediate treatment. Ultrasound Doppler is recognized as the preferred imaging modality for testicular torsion due to its high specificity, sensitivity and availability. OBJECTIVES: To determine the accuracy of ultrasound Doppler in diagnosis of torsion of undescended testis. METHODS: We describe three patients with known undescended testis who were admitted with groin pain and had preoperative ultrasound Doppler. The discrepancy between these and the intraoperative findings is discussed. RESULTS: In two patients incarcerated inguinal hernia was diagnosed with ultrasound Doppler; however, surgery revealed torsion of an undescended testis. In the third patient ultrasound Doppler diagnosed torsion of undescended testis, but at surgery incarcerated inguinal hernia was found, without evidence of testicular torsion. CONCLUSIONS: Torsion of undescended testis should be a clinical rather than radiologic diagnosis. PMID- 17348482 TI - Survey on the use of function assessment and outcome measures in rehabilitation facilities in Israel (SUFA 2004). AB - BACKGROUND: Measurement of function is an essential component of routine rehabilitation work (mainly for quantifying function at different phases in the rehabilitation process), rehabilitation policy (admission and discharge criteria, length of stay in rehabilitation), goal setting, and outcome measurement. OBJECTIVE: To explore the scope of the scales used for function assessment by the various disciplines of rehabilitation medicine in rehabilitation facilities. METHOD: A structured questionnaire was sent to 36 rehabilitation facilities. Respondents were asked to specify the scales they use for functional assessment for each of 15 selected pathologies. Also examined were satisfaction with the scales, as well as the existence of a computerized database of routine function assessment in the facility and the willingness to create a national agreed "common data set" of the assessments. RESULTS: The general response rate was 86.1% (31 of 36 questionnaires were returned). For the sake of data presentation, rehabilitation facilities were classified into four categories: general, geriatric, pediatric, and community. Most facilities performed function assessment using a total of 125 scales. Heterogeneity was found between facilities and between pathologies. The highest number of scales was found in the area of neurologic pathologies. For most pathologies, assessment of impairment was used more than assessment of disability. Most facilities in the survey did not have a computerized database of function assessments. CONCLUSIONS: A common data set of function assessments in everyday clinical work would ensure standardization without necessarily limiting the use of additional scales and at the same time significantly minimize the current heterogeneity. PMID- 17348483 TI - Renal slit diaphragm--the open zipper and the failing heart. AB - Inherited forms of proteinuria constitute a rare and heterogeneous group of diseases, the most prominent of which is glomerular dysfunction, which leads to proteinuria. Investigation of the genetic background underlying these diseases has provided significant data on the normal operation of the glomerular filter. Among the different components of the glomerulus, the podocyte slit diaphragm is considered the main source for genetically derived protein alteration, which leads in turn to proteinuria. Investigation of the different proteins revealed that the lack of nephrin and podocin is the leading cause of several inherited forms of proteinuria. It was also proposed that the lack of podocin is linked to cardiac anomalies. This review suggests that the absence of slit diaphragm proteins and the open zipper phenomenon are associated with cardiac anomalies. PMID- 17348484 TI - Varicose veins: more than simply an esthetic problem. PMID- 17348485 TI - Acute occlusion of the abdominal aorta associated with lower limb paralysis. PMID- 17348486 TI - Neurosyphilis: the reemergence of an historical disease. PMID- 17348487 TI - Exceptional site of metastatic adenocarcinoma of the lung. PMID- 17348489 TI - Lengthening temporalis myoplasty for facial palsy reanimation. PMID- 17348488 TI - Prolonged fever due to silicone granulomatosis. PMID- 17348490 TI - Malignant esophagopleural fistula. PMID- 17348491 TI - Damage control on the combat field: old philosophy, new concept. PMID- 17348492 TI - Lipid-lowering therapy--benefits and risks. PMID- 17348493 TI - Radiation-induced hypoglossal nerve palsy. PMID- 17348494 TI - Internal solitons in the ocean and their effect on underwater sound. AB - Nonlinear internal waves in the ocean are discussed (a) from the standpoint of soliton theory and (b) from the viewpoint of experimental measurements. First, theoretical models for internal solitary waves in the ocean are briefly described. Various nonlinear analytical solutions are treated, commencing with the well-known Boussinesq and Korteweg-de Vries equations. Then certain generalizations are considered, including effects of cubic nonlinearity, Earth's rotation, cylindrical divergence, dissipation, shear flows, and others. Recent theoretical models for strongly nonlinear internal waves are outlined. Second, examples of experimental evidence for the existence of solitons in the upper ocean are presented; the data include radar and optical images and in situ measurements of wave forms, propagation speeds, and dispersion characteristics. Third, and finally, action of internal solitons on sound wave propagation is discussed. This review paper is intended for researchers from diverse backgrounds, including acousticians, who may not be familiar in detail with soliton theory. Thus, it includes an outline of the basics of soliton theory. At the same time, recent theoretical and observational results are described which can also make this review useful for mainstream oceanographers and theoreticians. PMID- 17348495 TI - Speech production knowledge in automatic speech recognition. AB - Although much is known about how speech is produced, and research into speech production has resulted in measured articulatory data, feature systems of different kinds, and numerous models, speech production knowledge is almost totally ignored in current mainstream approaches to automatic speech recognition. Representations of speech production allow simple explanations for many phenomena observed in speech which cannot be easily analyzed from either acoustic signal or phonetic transcription alone. In this article, a survey of a growing body of work in which such representations are used to improve automatic speech recognition is provided. PMID- 17348496 TI - Comment on "Analysis of the time-reversal operator for scatterers of finite size," by D. H. Chambers [J. Acoust. Soc. Am. 112, 411-419 (2002)]. AB - This letter concerns the paper "Analysis of the time-reversal operator for scatterers of finite size" [J. Acoust. Soc. Am. 112, 411-419 (2002)]. The number of possible eigenvalues and eigenfunctions of the time reversal operator for a finite sphere given in the paper is much more than the correct number, which is proven to be the total number of multipole moments induced inside the finite sphere. PMID- 17348497 TI - Analysis of voice source characteristics using a constrained polynomial representation of voice source signals. AB - To analyze the characteristics of voice source signals from speech, a model is presented in the form of polynomial function by expanding the definition of the Rosenberg model. In combination with the all-pole assumption of the vocal-tract filter, methods are described for the pitch-synchronous speech analysis and temporal search of the glottal opening and closing instants. Because the source and filter models are both linear, the parameter estimation problem can be conveniently solved. In addition, the temporal search method can refine the locations of the glottal events and improve the accuracy of the parameter estimation. Analyses of non-nasalized voiced speech are conducted using an electroglottographic device from which the initial estimate of the temporal information is given. PMID- 17348498 TI - Echolocation clicks from killer whales (Orcinus orca) feeding on herring (Clupea harengus). AB - Echolocation clicks from Norwegian killer whales feeding on herring schools were recorded using a four-hydrophone array. The clicks had broadband bimodal frequency spectra with low and high frequency peaks at 24 and 108 kHz, respectively. The -10 dB bandwidth was 35 kHz. The average source level varied from 173 to 202 dB re 1 microPa (peak-to-peak) at 1 m. This is considerably lower than source levels described for Canadian killer whales foraging on salmon. It is suggested that biosonar clicks of Norwegian killer whales are adapted for localization of prey with high target strength and acute hearing abilities. PMID- 17348499 TI - Scattering of a Bessel beam by a sphere. AB - The exact scattering by a sphere centered on a Bessel beam is expressed as a partial wave series involving the scattering angle relative to the beam axis and the conical angle of the wave vector components of the Bessel beam. The sphere is assumed to have isotropic material properties so that the nth partial wave amplitude for plane wave scattering is proportional to a known partial-wave coefficient. The scattered partial waves in the Bessel beam case are also proportional to the same partial-wave coefficient but now the weighting factor depends on the properties of the Bessel beam. When the wavenumber-radius product ka is large, for rigid or soft spheres the scattering is peaked in the backward and forward directions along the beam axis as well as in the direction of the conical angle. These properties are geometrically explained and some symmetry properties are noted. The formulation is also suitable for elastic and fluid spheres. A partial wave expansion of the Bessel beam is noted. PMID- 17348500 TI - An annular superposition integral for axisymmetric radiators. AB - A fast integral expression for computing the nearfield pressure is derived for axisymmetric radiators. This method replaces the sum of contributions from concentric annuli with an exact double integral that converges much faster than methods that evaluate the Rayleigh-Sommerfeld integral or the generalized King integral. Expressions are derived for plane circular pistons using both continuous wave and pulsed excitations. Several commonly used apodization schemes for the surface velocity distribution are considered, including polynomial functions and a "smooth piston" function. The effect of different apodization functions on the spectral content of the wave field is explored. Quantitative error and time comparisons between the new method, the Rayleigh-Sommerfeld integral, and the generalized King integral are discussed. At all error levels considered, the annular superposition method achieves a speed-up of at least a factor of 4 relative to the point-source method and a factor of 3 relative to the generalized King integral without increasing the computational complexity. PMID- 17348501 TI - Numerical evaluation of the acoustic radiation from planar structures with general baffle conditions using wavelets. AB - A method is presented for computing the acoustic radiation from baffled, unbaffled, or partially baffled planar structures. The surface displacement and the surface pressure are expressed in terms of wavelets, and the acoustic dynamic stiffness (baffled case) or the acoustic receptance (unbaffled case) between any two wavelets is derived in closed form. The wavelets are employed with translation only (i.e., no dilation), and the jinc function is used; the Hankel transform of this function is the Heavyside step function, and this feature greatly simplifies the analysis. There is a trivial mapping between the wavelet amplitudes and the physical motion of the structure, and hence the dynamic stiffness and receptance results can readily be used to derive the acoustic dynamic stiffness matrix (by inverting the receptance matrix in the unbaffled case) in any set of generalized coordinates. Partially baffled systems can then be studied by substructuring the dynamic stiffness matrix. A set of example problems is considered in which the method is used to compute the resistive and reactive radiation efficiency of a range of benchmark systems. PMID- 17348502 TI - Manipulation of micrometer sized particles within a micromachined fluidic device to form two-dimensional patterns using ultrasound. AB - Ultrasonic manipulation, which uses acoustic radiation forces, is a contactless manipulation technique. It allows the simultaneous handling of single or numerous particles (e.g., copolymer beads, biological cells) suspended in a fluid, without the need for prior localization. Here it is reported on a method for two dimensional arraying based on the superposition of two in-plane orthogonally oriented standing pressure waves. A device has been built and the experimental results have been compared with a qualitative analytical model. A single piezoelectric transducer is used to excite the structure to vibration, which consists of a square chamber etched in silicon sealed with a glass plate. A set of orthogonally aligned electrodes have been defined on one surface of the piezoelectric. This allows either a quasi-one-dimensional standing pressure field to be excited in one of two directions or if both electrodes are activated simultaneously a two-dimensional pressure field to be generated. Two different operational modes are presented: two signals identical in amplitude and frequency were used to trap particles in oval shaped clumps; two signals with slightly different frequencies to trap particles in circular clumps. The transition between the two operational modes is also investigated. PMID- 17348503 TI - Bubble interaction dynamics in Lagrangian and Hamiltonian mechanics. AB - Two models of interacting bubble dynamics are presented, a coupled system of second-order differential equations based on Lagrangian mechanics, and a first order system based on Hamiltonian mechanics. Both account for pulsation and translation of an arbitrary number of spherical bubbles. For large numbers of interacting bubbles, numerical solution of the Hamiltonian equations provides greater stability. The presence of external acoustic sources is taken into account explicitly in the derivation of both sets of equations. In addition to the acoustic pressure and its gradient, it is found that the particle velocity associated with external sources appears in the dynamical equations. PMID- 17348504 TI - Mode detection in turbofan inlets from near field sensor arrays. AB - Knowledge of the modal content of the sound field radiated from a turbofan inlet is important for source characterization and for helping to determine noise generation mechanisms in the engine. An inverse technique for determining the mode amplitudes at the duct outlet is proposed using pressure measurements made in the near field. The radiated sound pressure from a duct is modeled by directivity patterns of cut-on modes in the near field using a model based on the Kirchhoff approximation for flanged ducts with no flow. The resulting system of equations is ill posed and it is shown that the presence of modes with eigenvalues close to a cutoff frequency results in a poorly conditioned directivity matrix. An analysis of the conditioning of this directivity matrix is carried out to assess the inversion robustness and accuracy. A physical interpretation of the singular value decomposition is given and allows us to understand the issues of ill conditioning as well as the detection performance of the radiated sound field by a given sensor array. PMID- 17348506 TI - An equivalent roughness model for seabed backscattering at very high frequencies using a band-matrix approach. AB - This work concerns modeling of very high frequency (>100 kHz) sonar images obtained from a sandy seabed. The seabed is divided into a discrete number of ID height profiles. For each height profile the backscattered pressure is computed by an integral equation method for interface scattering between two homogeneous media as formulated by Chan [IEEE Trans. Antennas Propag. 46, 142-149 (1998)]. However, the seabed is inhomogeneous, and volume scattering is a major contributor to backscattering. The SAX99 experiments revealed that the density in the unconsolidated sediment within the first 5 mm exhibits a high spatial variation. For that reason, additional roughness is introduced: For each surface point a stochastic realization of the density along the vertical is generated, and the sediment depth at which the density has its maximum value will constitute the new height field value. The matrix of the full integral equation is reduced to a band matrix as the interaction between the point sources on the seabed is neglected from a certain range; this allows computations on long height profiles with lengths up to approximately 25 m (at 300 kHz). The equivalent roughness approach, combined with the band-matrix approach, agrees with SAX99 data at 300 kHz. PMID- 17348505 TI - A single-scattering correction for large contrasts in elastic layers. AB - The single-scattering solution is implemented in a formulation that makes it possible to accurately handle solid-solid interfaces with the parabolic equation method. Problems involving large contrasts across sloping stratigraphy can be handled by subdividing a vertical interface into a series of two or more scattering problems. The approach can handle complex layering and is applicable to a large class of seismic problems. The solution of the scattering problem is based on an iteration formula, which has improved convergence in the new formulation, and the transverse operator of the parabolic wave equation, which is implemented efficiently in terms of banded matrices. Accurate solutions can often be obtained by using only one iteration. PMID- 17348507 TI - Evidence of dispersion in an artificial water-saturated sand sediment. AB - A laboratory experiment was conducted to measure the speed of sound in an artificial water-saturated granular sediment composed of cleaned and sorted medium-grained sand and degassed distilled water. The experiment was conducted within a range of frequencies where dispersion is predicted by a number of existing models. Between 2 and 4 kHz, the sound speed was inferred from measurements of the resonance frequencies of a thin-walled cylindrical container filled with the material. An elastic waveguide model was used to account for the effect of the finite impedance of the walls, although this effect was found to be small. From 20 to 300 kHz, the sound speed was obtained directly from time-of flight measurements within the sediment. Dispersion in close agreement with the Williams effective density fluid model [K. L. Williams, J. Acoust. Soc. Am. 110, 2276-2281 (2001)] was observed. PMID- 17348509 TI - Underwater implosion of glass spheres. AB - Underwater implosion experiments were conducted with thin-wall glass spheres to determine the influence that structural failure has on the pressure pulse. Four experiments were conducted with glass spheres having an outside diameter of 7.62 cm, thickness of 0.762 mm, and an estimated buckling pressure of 7.57 MPa. The experiments were performed in a pressure vessel at a hydrostatic pressure of 6.996 MPa. The average peak pressure of the implosion pressure pulse was 26.1 MPa, measured at a radial distance of 10.16 cm from the sphere center. A computational fluid structure interaction model was developed to assess how the failure rate of the glass structure influences the pressure time history. The model employed a specified glass failure sequence that is uniform in time and space. It was found that for the conditions of the test, a glass failure rate of 275 m/s provided a reasonable representation of the test data. The test data and the model results show that the failure time history of the structure has a significant influence on an implosion pressure pulse. Computational prediction of an implosion pressure pulse needs to include the failure time history of the structure; otherwise it will overpredict the pressure time history. PMID- 17348508 TI - Estimating parameter uncertainties in matched field inversion by a neighborhood approximation algorithm. AB - In Bayesian inversion, the solution is characterized by its posterior probability density (PPD). A fast Gibbs sampler (FGS) has been developed to estimate the multi-dimensional integrals of the PPD, which requires solving the forward models many times and leads to intensive computation for multi-frequency or range dependent inversion cases. This paper presents an alternative approach based on a neighborhood approximation Bayes (NAB) algorithm. For lower dimension geoacoustic inversion, the NAB can approximate the PPD very well. For higher dimensional problems and sensitive parameters, however, the NAB algorithm has difficulty estimating the PPD accurately with limited model samples. According to the preliminary PPD estimation from the NAB, this paper developed a multi-step inversion scheme, which adjusts the parameter search intervals flexibly, in order to improve the approximation accuracy of the NAB and obtain more complete parameter uncertainties. The prominent feature of the NAB is to approximate the PPD by incorporating all models for which the forward problem has been solved into the appraisal stage. Comparison of the FGS and NAB for noisy synthetic benchmark test cases and Mediterranean real data indicates that the NAB provides reasonable estimates of the PPD moments while requiring significantly less computation time. PMID- 17348510 TI - The effect of cavity geometry on the nucleation of bubbles from cavities. AB - The heterogeneous nucleation of gas bubbles from cavities in a surface in contact with a liquid is a widely recognized phenomenon. This process has previously been theoretically analyzed extensively for a conical crevice, although in practice a wide range of cavity geometries might be expected. The method of analysis originally presented by Atchley and Prosperetti [J. Acoust. Soc. Am. 86, 1065 1084 (1989)] for the unstable growth of a gas-liquid interface in a conical crevice is here extended to any axisymmetric cavity geometry and four such different geometries are analyzed. Although the method presented neglects gas transfer, and therefore is most directly suitable for acoustic cavitations, this method is still valuable in comparing the nucleation behavior of different cavity types. It is found that once the interface has emerged outside the cavity, its behavior is determined by the size of the cavity's opening. Given that the behavior of the interface once it is outside the cavity will also be determined by the local flow conditions, the threshold for unstable growth of the interface inside the cavity leading to its emergence is the important value and will determine differences between cavity geometries in practice, as shown in the examples presented. PMID- 17348511 TI - Model for continuously scanning ultrasound vibrometer sensing displacements of randomly rough vibrating surfaces. AB - An analytic model is developed for the time-dependent ultrasound field reflected off a randomly rough vibrating surface for a continuously scanning ultrasound vibrometer system in bistatic configuration. Kirchhoff's approximation to Green's theorem is applied to model the three-dimensional scattering interaction of the ultrasound wave field with the vibrating rough surface. The model incorporates the beam patterns of both the transmitting and receiving ultrasound transducers and the statistical properties of the rough surface. Two methods are applied to the ultrasound system for estimating displacement and velocity amplitudes of an oscillating surface: incoherent Doppler shift spectra and coherent interferometry. Motion of the vibrometer over the randomly rough surface leads to time-dependent scattering noise that causes a randomization of the received signal spectrum. Simulations with the model indicate that surface displacement and velocity estimation are highly dependent upon the scan velocity and projected wavelength of the ultrasound vibrometer relative to the roughness height standard deviation and correlation length scales of the rough surface. The model is applied to determine limiting scan speeds for ultrasound vibrometer measuring ground displacements arising from acoustic or seismic excitation to be used in acoustic landmine confirmation sensing. PMID- 17348512 TI - Acoustoelastic analysis of reflected waves in nearly incompressible, hyper elastic materials: forward and inverse problems. AB - Many materials (e.g., rubber or biologic tissues) are "nearly" incompressible and often assumed to be incompressible in their constitutive equations. This assumption hinders realistic analyses of wave motion including acoustoelasticity. In this study, this constraint is relaxed and the reflected waves from nearly incompressible, hyper-elastic materials are examined. Specifically, reflection coefficients are considered from the interface of water and uni-axially prestretched rubber. Both forward and inverse problems are experimentally and analytically studied with the incident wave perpendicular to the interface. In the forward problem, the wave reflection coefficient at the interface is evaluated with strain energy functions for nearly incompressible materials in order to compute applied strain. For the general inverse problem, mathematical relations are derived that identify both uni-axial strains and normalized material constants from reflected wave data. The validity of this method of analysis is demonstrated via an experiment with stretched rubber. Results demonstrate that applied strains and normalized material coefficients can be simultaneously determined from the reflected wave data alone if they are collected at several different (but unknown) levels of strain. This study therefore indicates that acoustoelasticity, with an appropriate constitutive formulation, can determine strain and material properties in hyper-elastic, nearly incompressible materials. PMID- 17348513 TI - Granular layers on vibrating plates: effective bending stiffness and particle size effects. AB - Acoustic methods of land mine detection rely on the vibrations of the top plate of the mine in response to sound. For granular soil (e.g., sand), the particle size is expected to influence the mine response. This hypothesis is studied experimentally using a plate loaded with dry sand of various sizes from hundreds of microns to a few millimeters. For low values of sand mass, the plate resonance decreases with added mass and eventually reaches a minimum without particle size dependence. After the minimum, a frequency increase is observed with additional mass that includes a particle-size effect. Analytical nondissipative continuum models for granular media capture the observed particle-size dependence qualitatively but not quantitatively. In addition, a continuum-based finite element model (FEM) of a two-layer plate is used, with the sand layer replaced by an equivalent elastic layer for evaluation of the effective properties of the layer. Given a thickness of sand layer and corresponding experimental resonance, an inverse FEM problem is solved iteratively to give the effective Young's modulus and bending stiffness that matches the experimental frequency. It is shown that a continuum elastic model must employ a thickness-dependent elastic modulus in order to match experimental values. PMID- 17348514 TI - A study of vibroacoustic coupling between a pump and attached water-filled pipes. AB - This paper presents a model for the vibroacoustical behavior of a pump coupled with water-filled pipes. Coupling between (a) the pump and the inlet and outlet pipes, and (b) the pipe wall and the fluid contained in the pipe, is investigated through analytical modeling and numerical simulation. In the model, the pump is represented by a rigid body supported by multiple elastic mounts, and the inlet and outlet pipes by two semi-infinite water-filled pipes. The vibration characteristics of the coupled system under the excitation of mechanical forces and fluid-borne forces at the pump are calculated. The results enhance our understanding about how the input mechanical and fluid excitation energy at the pump is transmitted to the pipes and how to relate the piping vibroacoustical response to the excitations at the pump. This study assists in predicting dynamic stress in pipes for given excitations at the pump, and in developing methods to identify the nature (fluid or mechanical) of the excitation forces at the pump using the vibration and dynamic pressure measurements on the pump/pipe system. PMID- 17348515 TI - On the diffuse field reciprocity relationship and vibrational energy variance in a random subsystem at high frequencies. AB - A recent paper has shown that under certain conditions the cross-spectral matrix of the forces exerted by a vibrational or acoustic wave field on its surrounding boundaries can be expressed in terms of (i) the energy of the wave field, and (ii) the direct field dynamic stiffness matrix of the boundary. This "diffuse field reciprocity relation" was derived using wave mechanics, and it is not immediately clear how the required wave field properties translate to conditions on the vibrational modes of the system or the applied forcing. This issue is addressed here by deriving an extended version of the reciprocity relation using modal methods, and the conditions required for the extended version to reduce to the existing relation are delineated. It is shown that the existing diffuse field reciprocity relation leads to an anomalous result when used to predict the energy variance of a subsystem, and that this anomaly is resolved by using the present extended version of the relation. A supplementary result arising from the analysis is that for systems with a sufficient degree of randomness the ensemble average of the dynamic stiffness matrix of a random subsystem is equal to the inverse of the ensemble average of the receptance matrix. PMID- 17348516 TI - Radiation clusters and the active control of sound transmission into a symmetric enclosure. AB - Radiation cluster control is proposed for the purpose of attenuating harmonic sound transmission into a symmetric enclosure using error signals derived from structural vibration sensors. The approach falls into a category of middle authority control, which is between LAC (low authority control: structural modal control) and HAC (high authority control: radiation modal control), possessing the benefit of practicality over LAC, while providing high control performance and some flexibility of control gain assignment similar to HAC. The structure of a radiation cluster control system is outlined, showing that it is possible to control a target cluster without affecting the other clusters. A design procedure for the radiation cluster control system is then proposed. Numerical results are also presented. PMID- 17348517 TI - Use of principle velocity patterns in the analysis of structural acoustic optimization. AB - This work presents an application of principle velocity patterns in the analysis of the structural acoustic design optimization of an eight ply composite cylindrical shell. The approach consists of performing structural acoustic optimizations of a composite cylindrical shell subject to external harmonic monopole excitation. The ply angles are used as the design variables in the optimization. The results of the ply angle design variable formulation are interpreted using the singular value decomposition of the interior acoustic potential energy. The decomposition of the acoustic potential energy provides surface velocity patterns associated with lower levels of interior noise. These surface velocity patterns are shown to correspond to those from the structural acoustic optimization results. Thus, it is demonstrated that the capacity to design multi-ply composite cylinders for quiet interiors is determined by how well the cylinder be can designed to exhibit particular surface velocity patterns associated with lower noise levels. PMID- 17348518 TI - Optimization of a clamped plate silencer. AB - A previous theoretical study [L. Huang, J. Acoust. Soc. Am. 119, 2628-2638 (2006)] shows that, in a duct, a simply supported plate covering a side-branch rigid cavity can function effectively as a wave reflector over a broad range of low to medium frequencies. In this study, analytical formulation is extended to the boundary condition of clamped plate, which is easier to implement in practice. The theoretical model is tested experimentally using balsawood, which has a very high stiffness to mass ratio. The spectral peaks and shapes of the measured TL are in agreement with those calculated theoretically, attempts are also made to account for the considerable sound absorption in the rig. Further numerical studies based on the validated model show that, for a uniform plate, the optimal stopband is narrower and the lower band limit is worse than that of the simply supported configuration. However, a wave reflector using nonuniform, clamped plates with thinner ends out-performs the simply supported configuration in every aspect. Analyses show that the improvement is attributed to the increased acoustic radiation efficiency over the bulk length of the nonuniform plate, which behaves more like a rigid plate. PMID- 17348519 TI - Comparison of two modeling approaches for highly heterogeneous porous media. AB - The purpose of this paper is to study the acoustic behavior of highly heterogeneous, low density porous structures having a complex pore size distribution using two distinct theoretical approaches. The first approach requires the direct numerical integration of the Biot viscosity correction function. The main requirement here is a knowledge of the probability density function of the pore size, which can be achieved by an optical pore-counting technique. The fact that the observed pore size distribution in these materials could be distinctively split into two parts suggested the use of the second approach based upon the double-porosity theory by Olny and Boutin [J. Acoust. Soc. Am. 114(1), 73-89 (2003)]. The latter approach assumes a low permeability contrast between the two porous scales so that the acoustic properties could be estimated using the semi-phenomenological models of Johnson and Lafarge for the viscous and thermal dynamic permeabilities. Numerical results predicted by the two models are then compared with impedance tube experimental data showing good accuracy of the selected prediction methods. PMID- 17348520 TI - Source characterization of a subsonic jet by using near-field acoustical holography. AB - In the present study, patch near-field acoustical holography was used in conjunction with a multireference, cross-spectral sound pressure measurement to visualize the sound field emitted by a subsonic jet and to predict its farfield radiation pattern. A strategy for microphone array design is described that accounts for the low spatial coherence of aeroacoustic sources and for microphone self-noise resulting from entrained flow near the jet. In the experiments, a 0.8 cm-diameter burner was used to produce a subsonic, turbulent jet with a Mach number of 0.26. Six fixed, linear arrays holding eight reference microphones apiece were disposed circumferentially around the jet, and a circular array holding sixteen, equally spaced field microphones was traversed along the jet axis to measure the sound field on a 30-cm-diameter cylindrical surface enclosing the jet. The results revealed that the jet could be modeled as a combination of eleven uncorrelated dipole-, quadrupole-, and octupole-like sources, and the contribution of each source type to the total radiated sound power could be identified. Both the total sound field reconstructed in a three-dimensional space and the farfield radiation directivity obtained by using the latter model were successfully validated by comparisons to directly measured results. PMID- 17348521 TI - Theory of forward and reverse middle-ear transmission applied to otoacoustic emissions in infant and adult ears. AB - The purpose of this study is to understand why otoacoustic emission (OAE) levels are higher in normal-hearing human infants relative to adults. In a previous study, distortion product (DP) OAE input/output (I/O) functions were shown to differ at f2 = 6 kHz in adults compared to infants through 6 months of age. These DPOAE I/0 functions were used to noninvasively assess immaturities in forward/reverse transmission through the ear canal and middle ear [Abdala, C., and Keefe, D. H., (2006). J. Acoust Soc. Am. 120, 3832-3842]. In the present study, ear-canal reflectance and DPOAEs measured in the same ears were analyzed using a scattering-matrix model of forward and reverse transmission in the ear canal, middle ear, and cochlea. Reflectance measurements were sensitive to frequency-dependent effects of ear-canal and middle-ear transmission that differed across OAE type and subject age. Results indicated that DPOAE levels were larger in infants mainly because the reverse middle-ear transmittance level varied with ear-canal area, which differed by more than a factor of 7 between term infants and adults. The forward middle-ear transmittance level was -16 dB less in infants, so that the conductive efficiency was poorer in infants than adults. PMID- 17348522 TI - Basilar membrane tension calculations for the gerbil cochlea. AB - Anatomical studies suggest that the basilar membrane (BM) supports a radial tension, which is potentially important in cochlear mechanics. Assuming that the tension exists, we have calculated its magnitude from measurements of BM stiffness, longitudinal coupling, and geometry using a BM model. Results for the gerbil cochlea show that the tension decreases from the base to the apex of the cochlea and generates a tensile stress that is comparable in magnitude to the stress generated in other physiological systems. The model calculations are augmented by experiments that investigate the source of BM tension. The experimental results suggest that BM tension is maintained by the spiral ligament. PMID- 17348523 TI - Cochlear traveling-wave amplification, suppression, and beamforming probed using noninvasive calibration of intracochlear distortion sources. AB - Originally developed to estimate the power gain of the cochlear amplifier, so called "Allen-Fahey" and related experiments have proved invaluable for probing the mechanisms of wave generation and propagation within the cochlea. The experimental protocol requires simultaneous measurement of intracochlear distortion products (DPs) and ear-canal otoacoustic emissions (DPOAEs) under tightly controlled conditions. To calibrate the intracochlear response to the DP, Allen-Fahey experiments traditionally employ invasive procedures such as recording from auditory-nerve fibers or measuring basilar-membrane velocity. This paper describes an alternative method that allows the intracochlear distortion source to be calibrated noninvasively. In addition to the standard pair of primary tones used to generate the principal DP the noninvasive method employs a third, fixed tone to create a secondary DPOAE whose amplitude and phase provide a sensitive assay of the intracochlear value of the principal DP near its characteristic place. The method is used to perform noninvasive Allen-Fahey experiments in cat and shown to yield results in quantitative agreement with the original, auditory-nerve-based paradigm performed in the same animal. Data obtained using a suppression-compensated variation of the noninvasive method demonstrate that neither traveling-wave amplification nor two-tone suppression constitutes the controlling influence in DPOAE generation at close frequency ratios. Rather, the dominant factor governing the emission magnitude appears to be the variable directionality of the waves radiated by the distortion-source region, which acts as a distortion beamformer tuned by the primary frequency ratio. PMID- 17348524 TI - Physiological detection of interaural phase differences. AB - Auditory evoked cortical responses to changes in the interaural phase difference (IPD) were recorded using magnetoencephalography (MEG). Twelve normal-hearing young adults were tested with amplitude-modulated tones with carrier frequencies of 500, 1000, 1250, and 1500 Hz. The onset of the stimuli evoked P1m-N1m-P2m cortical responses, as did the changes in the interaural phase. Significant responses to IPD changes were identified at 500 and 1000 Hz in all subjects and at 1250 Hz in nine subjects, whereas responses were absent in all subjects at 1500 Hz, indicating a group mean threshold for detecting IPDs of 1250 Hz. Behavioral thresholds were found at 1200 Hz using an adaptive two alternative forced choice procedure. Because the physiological responses require phase information, through synchronous bilateral inputs at the level of the auditory brainstem, physiological "change" detection thresholds likely reflect the upper limit of phase synchronous activity in the brainstem. The procedure has potential applications in investigating impaired binaural processing because phase statistic applied to single epoch MEG data allowed individual thresholds to be obtained. PMID- 17348525 TI - Differences in loudness of positive and negative Schroeder-phase tone complexes as a function of the fundamental frequency. AB - Tone complexes with positive (m+) and negative (m-) Schroeder phase show large differences in masking efficiency. This study investigated whether the different phase characteristics also affect loudness. Loudness matches between m+ and m- complexes were measured as a function of (1) the fundamental frequency (f0) for different frequency bands in normal-hearing and hearing-impaired subjects, and (2) intensity level in normal-hearing subjects. In normal-hearing subjects, the level of the m+ stimulus was up to 10 dB higher than that of the corresponding m- stimulus at the point of equal loudness. The largest differences in loudness were found for levels between 20 and 60 dB SL. In hearing-impaired listeners, the difference was reduced, indicating the relevance of active cochlear mechanisms. Loudness matches of m+ and m- stimuli to a common noise reference (experiment 3) showed differences as a function of f0 that were in line with direct comparisons from experiment 1 and indicated additionally that the effect is mainly due to the specific internal processing of m+. The findings are roughly consistent with studies pertaining to masking efficiency and can probably not be explained by current loudness models, supporting the need for incorporating more realistic cochlea simulations in future loudness models. PMID- 17348526 TI - Variability and uncertainty in masking by competing speech. AB - This study investigated the role of uncertainty in masking of speech by interfering speech. Target stimuli were nonsense sentences recorded by a female talker. Masking sentences were recorded from ten female talkers and combined into pairs. Listeners' recognition performance was measured with both target and masker presented from a front loudspeaker (nonspatial condition) or with a masker presented from two loudspeakers, with the right leading the front by 4 ms (spatial condition). In Experiment 1, the sentences were presented in blocks in which the masking talkers, spatial configuration, and signal-to-noise (S-N) ratio were fixed. Listeners' recognition performance varied widely among the masking talkers in the nonspatial condition, much less so in the spatial condition. This result was attributed to variation in effectiveness of informational masking in the nonspatial condition. The second experiment increased uncertainty by randomizing masking talkers and S-N ratios across trials in some conditions, and reduced uncertainty by presenting the same token of masker across trials in other conditions. These variations in masker uncertainty had relatively small effects on speech recognition. PMID- 17348527 TI - Speech intelligibility in free field: spatial unmasking in preschool children. AB - This study introduces a new test (CRISP-Jr.) for measuring speech intelligibility and spatial release from masking (SRM) in young children ages 2.5-4 years. Study 1 examined whether thresholds, masking, and SRM obtained with a test designed for older children (CRISP) and CRISP-Jr. are comparable in 4 to 5-year-old children. Thresholds were measured for target speech in front, in quiet, and with a different-sex masker either in front or on the right. CRISP-Jr. yielded higher speech reception thresholds (SRTs) than CRISP, but the amount of masking and SRM did not differ across the tests. In study 2, CRISP-Jr. was extended to a group of 3-year-old children. Results showed that while SRTs were higher in the younger group, there were no age differences in masking and SRM. These findings indicate that children as young as 3 years old are able to use spatial cues in sound source segregation, which suggests that some of the auditory mechanisms that mediate this ability develop early in life. In addition, the findings suggest that measures of SRM in young children are not limited to a particular set of stimuli. These tests have potentially useful applications in clinical settings, where bilateral fittings of amplification devices are evaluated. PMID- 17348528 TI - The binaural performance of a cross-talk cancellation system with matched or mismatched setup and playback acoustics. AB - Cross-talk cancellation is a method for synthesizing virtual auditory space using loudspeakers. One implementation is the "Optimal Source Distribution" technique [T. Takeuchi and P. Nelson, J. Acoust. Soc. Am. 112, 2786-2797 (2002)], in which the audio bandwidth is split across three pairs of loudspeakers, placed at azimuths of +/-90 degrees, +/-15 degrees, and +/-3 degrees, conveying low, mid, and high frequencies, respectively. A computational simulation of this system was developed and verified against measurements made on an acoustic system using a manikin. Both the acoustic system and the simulation gave a wideband average cancellation of almost 25 dB. The simulation showed that when there was a mismatch between the head-related transfer functions used to set up the system and those of the final listener, the cancellation was reduced to an average of 13 dB. Moreover, in this case the binaural interaural time differences and interaural level differences delivered by the simulation of the optimal source distribution (OSD) system often differed from the target values. It is concluded that only when the OSD system is set up with "matched" head-related transfer functions can it deliver accurate binaural cues. PMID- 17348529 TI - Binaural interference and auditory grouping. AB - The phenomenon of binaural interference, where binaural judgments of a high frequency target stimulus are disrupted by the presence of a simultaneous low frequency interferer, can largely be explained using principles of auditory grouping and segregation. Evidence for this relationship comes from a number of previous studies showing that the manipulation of simultaneous grouping cues such as harmonicity and onset synchrony can influence the strength of the phenomenon. In this study, it is shown that sequential grouping cues can also influence whether binaural interference occurs. Subjects indicated the lateral position of a high-frequency sinusoidally amplitude-modulated (SAM) tone containing an interaural time difference. Perceived lateral positions were reduced by the presence of a simultaneous diotic low-frequency SAM tone, but were largely restored when the interferer was "captured" in a stream of identical tones. A control condition confirmed that the effect was not due to peripheral adaptation. The data lend further support to the idea that binaural interference is affected by processes related to the perceptual organization of auditory information. Modifications to existing grouping-based models are proposed that may help account for binaural interference effects more successfully. PMID- 17348530 TI - The detection of differences in the cues to distance by elderly hearing-impaired listeners. AB - This experiment measured the capability of hearing-impaired individuals to discriminate differences in the cues to the distance of spoken sentences. The stimuli were generated synthetically, using a room-image procedure to calculate the direct sound and first 74 reflections for a source placed in a 7 x 9 m room, and then presenting each of those sounds individually through a circular array of 24 loudspeakers. Seventy-seven listeners participated, aged 22-83 years and with hearing levels from -5 to 59 dB HL. In conditions where a substantial change in overall level due to the inverse-square law was available as a cue, the elderly hearing-impaired listeners did not perform any different from control groups. In other conditions where that cue was unavailable (so leaving the direct-to reverberant relationship as a cue), either because the reverberant field dominated the direct sound or because the overall level had been artificially equalized, hearing-impaired listeners performed worse than controls. There were significant correlations with listeners' self-reported distance capabilities as measured by the "Speech, Spatial, and Qualities of Hearing" questionnaire [S. Gatehouse and W. Noble, Int. J. Audiol. 43, 85-99 (2004)]. The results demonstrate that hearing-impaired listeners show deficits in the ability to use some of the cues which signal auditory distance. PMID- 17348531 TI - Effective compression and noise reduction configurations for hearing protectors. AB - The author proposed to adopt wide dynamic range compression and adaptive multichannel modulation-based noise reduction algorithms to enhance hearing protector performance. Three experiments were conducted to investigate the effects of compression and noise reduction configurations on the amount of noise reduction, speech intelligibility, and overall preferences using existing digital hearing aids. In Experiment 1, sentence materials were recorded in speech spectrum noise and white noise after being processed by eight digital hearing aids. When the hearing aids were set to 3:1 compression, the amount of noise reduction achieved was enhanced or maintained for hearing aids with parallel configurations, but reduced for hearing aids with serial configurations. In Experiments 2 and 3, 16 normal-hearing listeners' speech intelligibility and perceived sound quality were tested when they listened to speech recorded through hearing aids with parallel and serial configurations. Regardless of the configuration, the noise reduction algorithms reduced the noise level and maintained speech intelligibility in white noise. Additionally, the listeners preferred the parallel rather than the serial configuration in 3:1 conditions and the serial configuration in 1:1 rather than 3:1 compression when the noise reduction algorithms were activated. Implications for hearing protector and hearing aid design are discussed. PMID- 17348532 TI - Coherent structures of the near field flow in a self-oscillating physical model of the vocal folds. AB - Current theories of voice production depend critically upon knowledge of the near field flow which emanates from the glottis. While most modern theories predict complex, three-dimensional structures in the near field flow, few investigations have attempted to quantify such structures. Using methods of flow visualization and digital particle image velocimetry, this study measured the near field flow structures immediately downstream of a self-oscillating, physical model of the vocal folds, with a vocal tract attached. A spatio-temporal analysis of the structures was performed using the method of empirical orthogonal eigenfunctions. Some of the observed flow structures included vortex generation, vortex convection, and jet flapping. The utility of such data in the future development of more accurate, low-dimensional models of voice production is discussed. PMID- 17348533 TI - Influence of acoustic loading on an effective single mass model of the vocal folds. AB - Three-way interactions between sound waves in the subglottal and supraglottal tracts, the vibrations of the vocal folds, and laryngeal flow were investigated. Sound wave propagation was modeled using a wave reflection analog method. An effective single-degree-of-freedom model was designed to model vocal-fold vibrations. The effects of orifice geometry changes on the flow were considered by enforcing a time-varying discharge coefficient within a Bernoulli flow model. The resulting single-degree-of-freedom model allowed for energy transfer from flow to structural vibrations, an essential feature usually incorporated through the use of higher order models. The relative importance of acoustic loading and the time-varying flow resistance for fluid-structure energy transfer was established for various configurations. The results showed that acoustic loading contributed more significantly to the net energy transfer than the time-varying flow resistance, especially for less inertive supraglottal loads. The contribution of supraglottal loading was found to be more significant than that of subglottal loading. Subglottal loading was found to reduce the net energy transfer to the vocal-fold oscillation during phonation, balancing the effects of the supraglottal load. PMID- 17348534 TI - An acoustic description of the vowels of northern and southern standard Dutch II: regional varieties. AB - An analysis is presented of regional variation patterns in the vowel system of Standard Dutch as spoken in the Netherlands (Northern Standard Dutch) and Flanders (Southern Standard Dutch). The speech material consisted of read monosyllabic utterances in a neutral consonantal context (i.e., /sVs/). The analyses were based on measurements of the duration and the frequencies of the first two formants of the vowel tokens. Recordings were made for 80 Dutch and 80 Flemish speakers, who were stratified for the social factors gender and region. These 160 speakers were distributed across four regions in the Netherlands and four regions in Flanders. Differences between regional varieties were found for duration, steady-state formant frequencies, and spectral change of formant frequencies. Variation patterns in the spectral characteristics of the long mid vowels /e o o/ and the diphthongal vowels /ei oey bacwards c u/ were in accordance with a recent theory of pronunciation change in Standard Dutch. Finally, it was found that regional information was present in the steady-state formant frequency measurements of vowels produced by professional language users. PMID- 17348535 TI - Acoustic cues discriminating german obstruents in place and manner of articulation. AB - This study focuses on the extraction of robust acoustic cues of labial and alveolar voiceless obstruents in German and their acoustic differences in the speech signal to distinguish them in place and manner of articulation. The investigated obstruents include the affricates [pf] and [ts], the fricatives [f] and [s] and the stops [p] and [t]. The target sounds were analyzed in word initial and word-medial positions. The speech data for the analysis were recorded in a natural environment, deliberately containing background noise to extract robust cues only. Three methods of acoustic analysis were chosen: (1) temporal measurements to distinguish the respective obstruents in manner of articulation, (2) static spectral characteristics in terms of logarithmic distance measure to distinguish place of articulation, and (3) amplitudinal analysis of discrete frequency bands as a dynamic approach to place distinction. The results reveal that the duration of the target phonemes distinguishes these in manner of articulation. Logarithmic distance measure, as well as relative amplitude analysis of discrete frequency bands, identifies place of articulation. The present results contribute to the question, which properties are robust with respect to variation in the speech signal. PMID- 17348536 TI - Voice F0 responses to pitch-shifted voice feedback during English speech. AB - Previous studies have demonstrated that motor control of segmental features of speech rely to some extent on sensory feedback. Control of voice fundamental frequency (F0) has been shown to be modulated by perturbations in voice pitch feedback during various phonatory tasks and in Mandarin speech. The present study was designed to determine if voice Fo is modulated in a task-dependent manner during production of suprasegmental features of English speech. English speakers received pitch-modulated voice feedback (+/-50, 100, and 200 cents, 200 ms duration) during a sustained vowel task and a speech task. Response magnitudes during speech (mean 31.5 cents) were larger than during the vowels (mean 21.6 cents), response magnitudes increased as a function of stimulus magnitude during speech but not vowels, and responses to downward pitch-shift stimuli were larger than those to upward stimuli. Response latencies were shorter in speech (mean 122 ms) compared to vowels (mean 154 ms). These findings support previous research suggesting the audio vocal system is involved in the control of suprasegmental features of English speech by correcting for errors between voice pitch feedback and the desired F0. PMID- 17348537 TI - Integration efficiency for speech perception within and across sensory modalities by normal-hearing and hearing-impaired individuals. AB - In face-to-face speech communication, the listener extracts and integrates information from the acoustic and optic speech signals. Integration occurs within the auditory modality (i.e., across the acoustic frequency spectrum) and across sensory modalities (i.e., across the acoustic and optic signals). The difficulties experienced by some hearing-impaired listeners in understanding speech could be attributed to losses in the extraction of speech information, the integration of speech cues, or both. The present study evaluated the ability of normal-hearing and hearing-impaired listeners to integrate speech information within and across sensory modalities in order to determine the degree to which integration efficiency may be a factor in the performance of hearing-impaired listeners. Auditory-visual nonsense syllables consisting of eighteen medial consonants surrounded by the vowel [a] were processed into four nonoverlapping acoustic filter bands between 300 and 6000 Hz. A variety of one, two, three, and four filter-band combinations were presented for identification in auditory-only and auditory-visual conditions: A visual-only condition was also included. Integration efficiency was evaluated using a model of optimal integration. Results showed that normal-hearing and hearing-impaired listeners integrated information across the auditory and visual sensory modalities with a high degree of efficiency, independent of differences in auditory capabilities. However, across-frequency integration for auditory-only input was less efficient for hearing-impaired listeners. These individuals exhibited particular difficulty extracting information from the highest frequency band (4762-6000 Hz) when speech information was presented concurrently in the next lower-frequency band (1890 2381 Hz). Results suggest that integration of speech information within the auditory modality, but not across auditory and visual modalities, affects speech understanding in hearing-impaired listeners. PMID- 17348538 TI - The effect of smoothing filter slope and spectral frequency on temporal speech information. AB - It is known that information contained within the filter skirts can provide cues important to speech intelligibility. However, the role of filter slope during temporal smoothing has received little attention. In experiment 1, smoothing filter slope angle was found to have a large effect on the intelligibility of sentences represented by three amplitude-modulated sinusoids. In experiment 2, the use of temporal cues above 16 Hz was examined across various regions of the spectrum. When increases in rate were presented to individual spectral bands, intelligibility only increased when presented in the higher spectral region. This result suggests a greater reliance on higher-rate cues in this region. However, intelligibility was greatest when these cues were distributed across the spectrum, indicating that their effective use is not restricted solely to this region. PMID- 17348539 TI - Singing proficiency in the general population. AB - Most believe that the ability to carry a tune is unevenly distributed in the general population. To test this claim, we asked occasional singers (n=62) to sing a well-known song in both the laboratory and in a natural setting (experiment 1). Sung performances were judged by peers for proficiency, analyzed for pitch and time accuracy with an acoustic-based method, and compared to professional singing. The peer ratings for the proficiency of occasional singers were normally distributed. Only a minority of the occasional singers made numerous pitch errors. The variance in singing proficiency was largely due to tempo differences. Occasional singers tended to sing at a faster tempo and with more pitch and time errors relative to professional singers. In experiment 2 15 nonmusicians from experiment 1 sang the same song at a slow tempo. In this condition, most of the occasional singers sang as accurately as the professional singers. Thus, singing appears to be a universal human trait. However, two of the occasional singers maintained a high rate of pitch errors at the slower tempo. This poor performance was not due to impaired pitch perception, thus suggesting the existence of a purely vocal form of tone deafness. PMID- 17348540 TI - A mechanistic analysis of stone fracture in lithotripsy. AB - In vitro experiments and an elastic wave model were used to analyze how stress is induced in kidney stones by lithotripsy and to test the roles of individual mechanisms-spallation, squeezing, and cavitation. Cylindrical U30 cement stones were treated in an HM-3-style lithotripter. Baffles were used to block specific waves responsible for spallation or squeezing. Stones with and without surface cracks added to simulate cavitation damage were tested in glycerol (a cavitation suppressive medium). Each case was simulated using the elasticity equations for an isotropic medium. The calculated location of maximum stress compared well with the experimental observations of where stones fractured in two pieces. Higher calculated maximum tensile stress correlated with fewer shock waves required for fracture. The highest calculated tensile stresses resulted from shear waves initiated at the proximal corners and strengthened along the side surfaces of the stone by the liquid-borne lithotripter shock wave. Peak tensile stress was in the distal end of the stone where fracture occurred. Reflection of the longitudinal wave from the distal face of the stone--spallation-produced lower stresses. Surface cracks accelerated fragmentation when created near the location where the maximum stress was predicted. PMID- 17348541 TI - The freshwater dolphin Inia geoffrensis geoffrensis produces high frequency whistles. AB - Because whistles are most commonly associated with social delphinids, they have been largely overlooked, ignored, or presumed absent, in solitary freshwater dolphin species. Whistle production in the freshwater dolphin, the boto (Inia geoffrensis geoffrensis), has been controversial. Because of its sympatry with tucuxi dolphins (Sotalia fluviatilis), a whistling species, some presume tucuxi whistles might have been erroneously assigned to the boto. Using a broadband recording system, we recorded over 100 whistles from boto dolphins in the Yasunf River, Ecuador, where the tucuxi dolphins are absent. Our results therefore provide conclusive evidence for whistle production in Inia geoffrensis geoffrensis. Furthermore, boto whistles are significantly different from tucuxi whistles recorded in nearby rivers. The Ecuadorian boto whistle has a significantly greater frequency range (5.30-48.10 kHz) than previously reported in other populations (Peru and Colombia) that were recorded with more bandwidth limited equipment. In addition, the top frequency and the range are greater than in any other toothed whale species recorded to date. Whistle production was higher during resting activities, alone or in the presence of other animals. The confirmation of whistles in the boto has important implications for the evolution of whistles in Cetacea and their association with sociality. PMID- 17348542 TI - Patterned burst-pulse vocalizations of the northern right whale dolphin, Lissodelphis borealis. AB - Vocalizations from the northern right whale dolphin, Lissodelphis borealis, were recorded during a combined visual and acoustic shipboard survey of cetacean populations off the west coast of the United States. Seven of twenty single species schools of L. borealis produced click and pulsed vocalizations. No whistles were detected during any of the encounters. Clicks associated with burst pulse vocalizations were lower in frequency and shorter in duration than clicks associated with echolocation. All burst-pulse sounds were produced in a series containing 6-18 individual burst-pulses. These burst-pulse series were stereotyped and repeated. A total of eight unique burst-pulse series were detected. Variation in the temporal characteristics of like units compared across repeated series was less than variation among all burst-pulses. These stereotyped burst-pulse series may play a similar communicative role as do stereotyped whistles found in other delphinid species. PMID- 17348543 TI - Spatial release from masking of aerial tones in pinnipeds. AB - In most masking experiments, target signals and sound intended to mask are located in the same position. Spatial release from masking (SRM) occurs when signals and maskers are spatially separated, resulting in detection improvement relative to when they are spatially co-located. In this study, SRM was investigated in a harbor seal, who naturally lacks pinnae, and California sea lion, who possesses reduced pinnae. Subjects had to detect aerial tones at 1, 8, and 16 kHz in the presence of octave bands of white noise centered at the tone frequency. While the masker occurred in front of the subject (0 degree), the tone occurred at 0, 45, or 90 degrees in the horizontal plane. Unmasked thresholds were also measured at these angles to determine sensitivity differences based on source azimuth. Compared to when signal and masker where co-located, masked thresholds were lower by as much as 19 and 12 dB in the harbor seal and sea lion, respectively, when signal and masker were separated. Masked threshold differences of the harbor seal were larger than those previously measured under water. Performance was consistent with some measurements collected on terrestrial animals but differences between subjects at the highest frequency likely reflect variations in pinna anatomy. PMID- 17348544 TI - Semi-analytical computation of the acoustic field of a segment of a cylindrically concave transducer in lossless and attenuating media. AB - Conventional ultrasound transducers used for medical diagnosis generally consist of linearly aligned rectangular apertures with elements that are focused in one plane. While traditional beamforming is easily accomplished with such transducers, the development of quantitative, physics-based imaging methods, such as tomography, requires an accurate, and computationally efficient, model of the field radiated by the transducer. The field can be expressed in terms of the Helmholtz-Kirchhoff integral; however, its direct numerical evaluation is a computationally intensive task. Here, a fast semianalytical method based on Stepanishen's spatial impulse response formulation [J. Acoust. Soc. Am. 49, 1627 1638 (1971)] is developed to compute the acoustic field of a rectangular element of cylindrically concave transducers in a homogeneous medium. The pressure field, for, lossless and attenuating media, is expressed as a superposition of Bessel functions, which can be evaluated rapidly. In particular, the coefficients of the Bessel series are frequency independent and need only be evaluated once for a given transducer. A speed up of two orders of magnitude is obtained compared to an optimized direct numerical integration. The numerical results are compared with Field II and the Fresnel approximation. PMID- 17348545 TI - Method for detecting small changes in vibrotactile perception threshold related to tactile acuity. AB - Two metrics, expressing the change in mechanoreceptor-specific vibrotactile thresholds at a fingertip over a time interval of months or years, and the shift in threshold from the mean values recorded from the fingertips of healthy persons, have been constructed for thresholds measured from individual fingers. The metrics assume the applicability of the acute adaptation property of mechanoreceptors, which has been confirmed by thresholds obtained from 18 forest workers on two occasions, separated by 5 years. Hence, when expressed in decibels, both threshold changes and threshold shifts may be averaged at frequencies mediated by the same receptor population to improve precision. Differences between threshold changes at frequencies mediated by the same receptor population may be used to identify inconsistent subject performance, and hence potentially erroneous results. For this group of subjects, the threshold changes and threshold shifts at frequencies believed mediated by the slowly adapting type I (SAI) (4 and 6.3 Hz) and rapidly adapting type I (FAI) (20 and 32 Hz) receptors within each finger were correlated. In these circumstances, which may be expected to occur for some work-induced and systemic peripheral neuropathies, both threshold changes and threshold shifts may be summed over SAI and FAI receptors to improve precision, and hence the potential for interpretation. PMID- 17348546 TI - Focus in production: tonal shape, intensity and word order. AB - The effect of word order and prosodic focus on the tonal shape and intensity in the production of prosody was studied. The results show that the production of focus in Finnish follows a global pattern with regard to tonal features. The relative pitch height difference between contrasted words is the most important pitch-related factor in signaling narrow prosodic focus. Narrow focus is not localized to prosodically emphasized words only but relates to the utterance as a whole. It was also found that syntactic structure with respect to both intensity and tonal structure modulated relative prosodic prominence of individual words. PMID- 17348547 TI - Drive-point functions and modal density. AB - It is well known that the real part of a drive-point function, averaged in frequency, can be estimated from the modal density and mass of a structure. Furthermore, the results are often the same as when the modal overlap is large due to damping or when the system boundaries are infinitely extended. The present note examines the possible use of modal density in estimating the imaginary part of the same system drive-point function. PMID- 17348548 TI - On the effect of error correlation on matched-field geoacoustic inversion. AB - The effect of correlated data errors on matched-field geoacoustic inversion for vertical array data is examined. The correlated errors stem from the inability to model the inhomogeneities in the environment resulting in an additional error term beyond ambient noise. Simulated data with these correlated errors are generated and then inverted with or without using the proper covariance matrix. Results show that the correlated error has a negative impact on geoacoustic parameter estimation if not accounted for properly. PMID- 17348549 TI - Acoustic virtual mass of granular media. AB - Mechanical coupling between grains in a randomly packed unconsolidated granular medium is shown to cause an increase in the effective inertia, hence, a reduction in sound and shear wave speeds, relative to predictions by the standard expressions for a uniform elastic solid. The effect may be represented as a virtual mass term, and directly related to the scintillation index of the grain to-grain contact stiffness. PMID- 17348550 TI - Loudness pattern-based speech quality evaluation using bayesian modeling and Markov chain Monte Carlo methods. AB - This work presents a speech quality evaluation method which is based on Moore and Glasberg's loudness model and Bayesian modeling. In the proposed method, the differences between the loudness patterns of the original and processed speech signals are employed as the observed features for representing speech quality, a Bayesian learning model is exploited as the cognitive model which maps the features into quality scores, and Markov chain Monte Carlo methods are used for the Bayesian computation. The performance of the proposed method was demonstrated through comparisons with the state-of-the-art speech quality evaluation standard, ITU-T P.862, using seven ITU subjective quality databases. PMID- 17348551 TI - Discrimination of starting phase with sinusoidal envelope modulation. AB - Modulation-filterbank models discard phase information above very low rates of amplitude modulation (AM). The present work evaluated this restriction by measuring thresholds for discriminating the starting phase of sinusoidal modulators of wideband-noise carriers. Results showed a low-pass characteristic with some listeners unable to perform the task once the modulation rate was greater than 12.5 Hz. For others, however, thresholds were obtained with AM rates of up to one to two octaves higher. Intersubject variability may in part relate to the presence of multiple discrimination cues, with only some based on comparison of the ongoing pattern of envelope fluctuation. PMID- 17348552 TI - Unattended speech processing: effect of vocal-tract length. AB - Rivenez et al. [J. Acoust. Soc. Am. 119 (6), 4027-4040 (2006)] recently demonstrated that an unattended message is able to prime by 28 ms a simultaneously presented attended message when the two messages have a different F0 range. This study asks whether a difference in vocal-tract length between the two messages rather than a difference in F0 can also produce such priming. A priming effect of 13 ms was found when messages were in the same F0 range but had different (15%-30%) vocal-tract length, suggesting that the processing of unattended speech strongly relies on the presence of perceptual grouping cues. PMID- 17348553 TI - Emergence of the acoustic Green's function from thermal noise. AB - The fluctuation-dissipation theorem is used to show how acoustic Green's functions corresponding to sound propagation in opposite directions between any two given points can be extracted from time series of thermal noise recorded at these points. The result applies to arbitrarily inhomogeneous, moving or motionless fluids with time-independent parameters, and demonstrates that the two point correlation function of thermal noise contains as much information about the environment as can be obtained acoustically by placing transceivers at the two points. PMID- 17348554 TI - The concept of minimally invasive dentistry. AB - This paper reviews Minimally Invasive Dentistry (MID) from a day-to-day dentistry perspective, focusing mostly on cariology and restorative dentistry, even though it embraces many aspects of dentistry. The concept of MID supports a systematic respect for the original tissue, including diagnosis, risk assessment, preventive treatment, and minimal tissue removal upon restoration. The motivation for MID emerges from the fact that fillings are not permanent and that the main reasons for failure are secondary caries and filling fracture. To address these flaws, there is a need for economical re-routing so that practices can survive on maintaining dental health and not only by operative procedures. PMID- 17348555 TI - Tooth development: 2. Regenerating teeth in the laboratory. AB - Tooth loss can occur for a number of reasons and a variety of prosthetic tooth replacement solutions are available to the dental practitioner. This article discusses current approaches in the use of tissue engineering to replace teeth or repair dental tissues. These strategies will depend upon the manipulation of stem cells in the laboratory and, whilst much progress has recently been made, it is likely that successful human tooth regeneration is still some years ahead. PMID- 17348556 TI - Modern restorative management of patients with congenitally missing teeth: 3. Conventional restorative options and considerations. AB - Restoration of spaces in hypodontia patients needs to take into account many factors including, the number of missing teeth, the distribution of space, the size of the teeth, and the age of the patient. This paper considers adhesive and conventional bridgework, as well as removal alternatives for the restoration of spaces. The various merits of each are discussed, together with treatment planning considerations for such cases. PMID- 17348557 TI - Patient-centred measures in dental practice: 2. Quality of life. AB - This paper describes the value and use of quality of life measures to dental practice, how to assess oral health-related quality of life in dental practice and how to interpret what they mean when assessing patients'oral health needs and evaluating outcomes from dental care. PMID- 17348558 TI - Scientific evidence for pre-adjusted edgewise mechanics. AB - The aim of this paper is to present scientific evidence for treatment mechanics with the pre-adjusted edgewise appliance. We have summarized findings from randomized and controlled clinical trials following a search of Medline and the Cochrane Clinical Trials Register (CCTR) 1970-June 2005. Evidence was available to support our choice of archwires, use of canine lacebacks and method of space closure, thus providing the beginning of a scientific basis for our day-to-day management of fixed appliance mechanics. PMID- 17348559 TI - Case report: oral manifestations and radiographic features of osteosarcoma. AB - Although osteosarcoma of the jaws is a rare tumour, early diagnosis is a prognostic determinant. Patients with osteosarcoma of the jaws are likely to present to the general dental practitioner initially, however, as the condition is uncommon, many dentists may be unfamiliar with its early radiographic features. PMID- 17348560 TI - The eosinophilic ulcer revisited. AB - This paper reviews the eosinophilic ulcer and presents a case of such an ulcer on the tongue of a young female patient. The stages involved in arriving at a differential diagnosis are discussed, along with management of the condition. PMID- 17348561 TI - A new route for dental graduates. AB - The two dental faculties believe that the new examination will provide a modern, fit-for-purpose, innovative assessment for today's young dentist. The introduction of a workplace-based portfolio removes the reliance on traditional tests of knowledge and, together with the OSCE elements, allows for triangulation of methods to test the areas set out in the GPT Curriculum. Furthermore, the faculties hope that the evaluation of workplace-based experience, and decreased reliance on traditional examination methods, will also have greater meaning for young dental graduates. PMID- 17348562 TI - Physical signs for the general dental practitioner. Case 41. Tongue-biting. PMID- 17348563 TI - Aspects of human disease. PMID- 17348564 TI - Modernising medical careers and the birth of postgraduate specialty schools of medicine. PMID- 17348566 TI - Consultant physicians in the U.K. PMID- 17348565 TI - Knowledge-based assessment pilot project. PMID- 17348567 TI - A doctor in the House of Lords. PMID- 17348568 TI - Future EU strategy on health services. PMID- 17348569 TI - Health sector reforms programme in Punjab: a primary healthcare initiative. AB - Punjab is the largest province of Pakistan with a population of over 85 million. Provision of equal access to primary healthcare is a mammoth task in this developing country with well known resource constraints. Punjab has a network of 2748 primary healthcare (PHC) facilities spread over an area of 205,345 km2. The Punjab government has initiated a two-year Health Sector Reforms Programme (HSRP) to make the primary healthcare network of 2456 basic health units and 292 rural health centres fully operational. Benefits of the programme for medical staff include a substantial salary and an incentive package combined with improved working and living conditions, a pre-service orientation programme and regular in service training, a supportive monitoring and supervisory mechanism, and periodic third party inspections. The strong political and administrative will to harness all available resources is the key to the success of the HSRP. All of the 35 district governments have signed terms of partnership with the provincial government to execute the programme. Preliminary reports show a rise in the recruitment of healthcare providers in remote rural facilities. PMID- 17348570 TI - Variations in the reporting of endoscopies by different endoscopists. AB - All gastroscopies and colonoscopies performed in two U.K. teaching hospitals over a period of one year were audited to investigate whether endoscopic reporting of gastroscopies and colonoscopies by different endoscopists is consistent. Endoscopic diagnoses were retrieved from the hospitals' endoscopy databases. The results of 1814 colonoscopies and 2127 gastroscopies were analysed using chi2 (Chi squared). The frequency of reporting common diagnoses was variable and the differences between specialist endoscopists were highly significant, including for important conditions such as peptic ulceration (range 2-10%, p = 0.001) and colonic polyps (16-45%, p < 0.001). There is a large variation in the frequency of the diagnoses reported by different endoscopists. This is unlikely to be explained by casemix or chance. This may have major implications for the health of patients. More emphasis must be placed during training on the correct interpretation of endoscopies. PMID- 17348571 TI - Modern management of atrial fibrillation. AB - Atrial fibrillation (AF) continues to offer a management challenge to physicians. The incidence of this arrhythmia is rising and the cost to the healthcare system is vast. Much of this health burden relates to the high risk of stroke and thromboembolism associated with AF. This review covers common treatment strategies employed in AF management, discusses relevant drug therapy and the role of electrophysiology or surgery. PMID- 17348572 TI - Venous return: cardiomythology? PMID- 17348573 TI - Web-based learning: pros, cons and controversies. AB - Advantages of web-based learning (WBL) in medical education include overcoming barriers of distance and time, economies of scale, and novel instructional methods, while disadvantages include social isolation, up-front costs, and technical problems. Web-based learning is purported to facilitate individualised instruction, but this is currently more vision than reality. More importantly, many WBL instructional designs fail to incorporate principles of effective learning, and WBL is often used for the wrong reasons (e.g., for the sake of technology). Rather than trying to decide whether WBL is superior to or equivalent to other instructional media (research addressing this question will always be confounded), we should accept it as a potentially powerful instructional tool, and focus on learning when and how to use it. Educators should recognise that high fidelity, multimedia, simulations, and even WBL itself will not always be necessary to effectively facilitate learning. PMID- 17348574 TI - Modern management of primary systemic vasculitis. PMID- 17348575 TI - Update on postmenopausal osteoporosis management. PMID- 17348576 TI - Sjogren's syndrome. PMID- 17348577 TI - B cell depletion in systemic lupus erythematosus. PMID- 17348578 TI - Crystal arthritis: contemporary approaches to diseases of antiquity. PMID- 17348579 TI - Myths of ageing. AB - Historical and contemporary images of ageing have generally reinforced negative stereotypes of old age. An examination of sculpture, painting, poetry, literature and film, as well as television, advertising, newspaper stories, birthday cards and road signs reveals that old age is often shown as being a time of loneliness, depression and physical decline. These conditions do occur but their prevalence and severity have been exaggerated. There are many myths of ageing that have been influenced by these representations: that old people with physical or cognitive decline are social problems; that families no longer care for their elders; that geriatric medicine is an unglamorous specialty. Low expectations of old people and ageist thinking can adversely affect how we speak of disadvantaged old people. The challenge is to question inaccurate assumptions. Key to the improvement of medical care of older people is to extend the teaching of geriatric medicine and improve and coordinate research. PMID- 17348580 TI - Medicine for an ageing population. PMID- 17348581 TI - Pandemic influenza--how would you and your hospital cope? PMID- 17348582 TI - Careers in clinical academic medicine: new opportunities or old threats? AB - Academic medicine may have been in crisis but it is now starting to flourish again. In the words of Eric Thomas: "Clinical academia has a rosy future if you really celebrate and respect it as an activity, if you ensure a supply of graduates committed to research, if you get the relationship right with the key partners, if you get the best facilities for prosecuting research". It looks as though many of these 'ifs' will now be fulfilled within the reforming agenda of MMC. PMID- 17348583 TI - Kikuchi's disease: an important cause of cervical lymphadenopathy. AB - Kikuchi's disease is a form of necrotising lymphadenitis typically presenting in young women with lymphadenopathy. A case of Kikuchi's disease is reported in order to highlight the diagnostic confusion that is often associated with the condition. The possibility of the disease should be taken into account in any patient presenting with unexplained lymphadenopathy, and consideration of the diagnosis is particularly important before the introduction of potentially inappropriate drug therapy. PMID- 17348584 TI - Mother and child care in art. PMID- 17348585 TI - Monitoring of cardiotoxicity during immunotherapy with Herceptin using simultaneous continuous wave Doppler depending on N-terminal pro-brain natriuretic peptide. PMID- 17348586 TI - A pain tool for people with communication difficulties is no closer. PMID- 17348587 TI - Tuberculosis: where are we going? PMID- 17348588 TI - A personal view of assisted dying. PMID- 17348589 TI - Healthcare in NHS hospitals. PMID- 17348590 TI - Should our medical records be automatically centralised? PMID- 17348591 TI - Full steam ahead for nurses' move into commissioning role. PMID- 17348592 TI - More options for mothers. PMID- 17348593 TI - Who does what and when? AB - The role of nurses as co-ordinators of care is investigated in the last in the series on Modernising Nursing Careers. PMID- 17348594 TI - Challenge the bullies. PMID- 17348595 TI - Experiences of patients with type 2 diabetes starting insulin therapy. AB - AIM: To explore the lived experience of patients with type 2 diabetes converting to insulin therapy. METHOD: An exploratory qualitative approach was adopted focusing on the phenomenon of patients with type 2 diabetes converting to insulin therapy. Individual interviews were conducted with eight patients who had been taking insulin for longer than one year. FINDINGS: Data analysis initially identified 25 themes, which were reduced to nine by connecting similar themes. Participants were not aware of the progressive nature of type 2 diabetes and the need for treatment to be changed to insulin therapy. The decision for insulin therapy to be initiated was usually made by the doctor. Participants were fearful of the thought of self-administering insulin injections, however, they adapted to this treatment and were still able to enjoy activities of daily living. Participants reported that they had a better understanding of their diabetes when they were taking insulin and were willing to share their knowledge with others. CONCLUSION: Living with a long-term condition like diabetes is stressful and requires commitment from individuals to self-manage. Participants taking insulin appeared more confident to manage their diabetes and adapted well to this change of treatment. PMID- 17348596 TI - Developing service provision for patients in primary care. AB - This article outlines the government's changes to the way that primary and community health services will be commissioned and provided. It also discusses the opportunities that exist for nurses to lead and develop services for the benefit of patients in the implementation of changes. PMID- 17348598 TI - Knee replacement surgery. PMID- 17348597 TI - Urinary tract infection: diagnosis and management for nurses. AB - Urinary tract infection (UTI) is a common health problem, so it is important that nurses in all care settings know how to manage patients with this condition effectively. This article defines UTI, identifying patients who are most at risk and the underlying reasons why. Accurate diagnosis is important in the provision of treatment and the prevention of further complications, some of which can have serious consequences for patients. Inappropriate investigations are expensive, and may result in patients being over-treated. UTI is multifaceted, which makes its management difficult. However, a good understanding of prevention, assessment and management can help nurses to ensure the right treatment is offered. PMID- 17348599 TI - Built on hope. PMID- 17348600 TI - Improving patient outcomes with prayer. AB - Matthew's et al.'s (2000) study supported the use of prayer in rheumatoid arthritis patients. The results of this study can be used to support the group's research utilization project to educate nurses about the impact religion and prayer can have on patient outcomes. A suggestion for future research is to include a more widespread age group, ranging from school age children up to the older adult, as study participants. Two feasability issues for educating nurses about the benefits of prayer on patient outcomes are the time and money. PMID- 17348601 TI - Utilization of the Stetler model: evaluating the scientific evidence on screening for postpartum depression risk factors in a primary care setting. PMID- 17348602 TI - Medical pharmacology: from review to planning. AB - The mission of medical pharmacology in the CHU (University Medical Centres) is to contribute, through research, instruction and treatment, to the development and optimal utilization of drugs. With a progressive development, medical pharmacology is now present in all CHUs, where its responsibilities are both hospital-related and university-related. This progressive development also explains why medical pharmacologists, regardless of their initial training, are recognized as drug experts. Continued growth of the discipline, in the context of changes in the hospital and university environment, should reinforce its position in the evaluation and proper use of drugs. PMID- 17348603 TI - What you need to know about the new regulations for biomedical research in France. AB - The EC 2001/20 directive relating to the clinical trials of medicinal products was transposed into French law in 2004 by means of a public health law. But this transposition actually came into effect on 27 August 2006 by the implementation of decree no. 2006-477 of 26 April 2006 which has been followed subsequently by numerous statutory orders. A reading of these regulatory texts shows that the new provisions go far beyond the framework of the directive as they have been notably extended by the French legislator to encompass all the health products within the competence of the French Agency for Sanitary Safety in Health Products (Afssaps) as well as to other studies that do not involve health products. In addition, all research undertaken is from now subject to the prior, and jointly favourable, reasoned opinion of a CPP (Ethic Committee) and authorisation by Afssaps. These new regulations for biomedical research in France substantially modify and reinforce the previous provisions defined by the Huriet law of 1988, for safety, vigilance and traceability. PMID- 17348604 TI - [Patients' and physicians' perceptions on participation in a clinical trial: results on a survey in a French hospital]. AB - OBJECTIVES: We report the first survey on French physicians and patients participating to assess motivations prior enrolment and benefits and constraints perceived after participation. METHOD: Twenty physicians were interviewed and 37 patients completed a questionnaire during clinical study participation. RESULTS: If the main patient's motivation is altruistic, physician wish their own patient feel better. After participation, patient is satisfied with being part of a research effort and contributing to medical science. Effect of trial treatment on physical well-being seems less pronounced. Main constraint is the randomisation to placebo group. For physicians, the main benefit is getting research experience and training. Main constraints are logistical. Otherwise, perceptions on the same clinical trial depend on participant. In fact, physician usually overestimates constraints of clinical trial for patient. CONCLUSION: The knowledge of patients and physicians perceptions of clinical trials and its taking into account should probably reduce difficulties in the recruitment in France. PMID- 17348605 TI - Use of the foreign studies: transposition of the results, prediction of the therapeutic effects in the french population, modelling of the public health interest. AB - More and more frequently, the health authorities and the French assessment agencies are led to issue Marketing Authorizations (MAs), give opinions on the eligibility for reimbursement of drugs or to draft recommendations for clinical practice based on the results of foreign studies. The results of these studies are more or less difficult to transpose to French practice. These difficulties generate varying degrees of uncertainty concerning the effect to be expected of a drug. A more or less extensive loss of effect is sometimes even predictable. Some of the difficulties in transposition are discussed in this article and proposals for action are made in order to allow one, in the long term, to predict in the most precise manner possible the effects to be expected from a drug in the French population and be able to verify this prediction at an interval from its eligibility for reimbursement. PMID- 17348606 TI - [Pain management of lung cancer patients by general practitioners]. AB - INTRODUCTION: This study evaluated the place of general practitioners (GP) in managing pain of lung cancer (LC) patients and their knowledge of specific guidelines. PATIENTS AND METHODS: Prospective study including LC patients presenting with pain with a need for WHO (World Health Organisation) level III medication. Pain evaluation (Brief Pain Inventory), current treatment and patients with doctor satisfaction were evaluated. Patients' GP were invited to answer a questionnaire. RESULTS: Fifty-nine patients (median age, 58 years), mainly stage IV Non Small Cell LC (n = 40) were included. Before treatment, 47 patients presented with moderate/severe pain which moderately/severely impacts on daily activities. Patients were mainly satisfied with their GP. Fifty-six GP were questioned (35 answered, 62.5%). Twenty-four known guidelines but no one had a specific training for pain management. Twenty-five used visual analogical scales for pain evaluation but morphine's prescription largely varies when compared with guidelines. CONCLUSIONS: Pain management for lung cancer patients seems always perfectible and development of specific training represents a pragmatic short term objective. PMID- 17348607 TI - [The use of triptan in ambulatory medicine in Midi-Pyrenees Region: clinical and pharmacological contra-indications and drug abuse]. AB - OBJECTIVE: Evaluate triptan prescriptions in ambulatory medicine. METHODS: Collection of medical data from 301 patients treated with triptans reimbursed by the French National Health Fund in the region of Midi-Pyrenees. RESULTS: Ninety five per cent of selected patients suffered from migraine condition according to the International Headache Society diagnosis criteria [Confidence interval (CI) 95%: 93-98]. Co-morbidity factors contra-indicating triptan therapy were present in 6% of patients (CI 95%: 3-9). 2% of patients were prescribed other medicinal products contra-indicated with their triptan therapy (CI 95%: 0-4). Twenty-six per cent of patients were taking triptan medicines more than 8 times per month over a period of three months (CI 95%: 21-31) and 8% were taking this treatment more than 12 times per month (CI 95%: 5-1 I). Eleven per cent kept written information of their migraine crises (CI 95%: 7-15). Thirty-nine per cent benefited from dedicated prophylactic treatments (CI 95%: 33-45). CONCLUSION: In a context of sustained increase in prescriptions of migraine treatments, it appears necessary to remain cautious about clinical and pharmacological contra indications. Prevention of abuse of medicines is based on a better use of crises agendas and introduction of prophylactic therapies. PMID- 17348608 TI - [Scoring pharmacodependence seriousness: a novel CEIP's evaluation tool]. AB - In France, the Afssaps is the body in charge of the evaluation of pharmacodependance. In order to fulfil its mission, the Afssaps has created a network of 10 Centres for Evaluation and Information on Pharmacodependance (CEIP), coordinated by the Drugs and Psychotropics Unit. Pharmacodependence notifications issued by professionals are collected by each Centre which evaluates them: it is therefore necessary to harmonize case reporting and make it possible to homogeneously evaluate the seriousness of pharmacodependence cases. Nantes CEIP has developed and has been routinely using a tool which evaluates pharmacodependence seriousness by quantifying patient consumption behaviour: the corresponding calculation, interpretation related to 3 patients is presented in this article. The association of clinical data generated by the tool, and official data coming from CEIP's, represents a powerful combination which is now available for pharmacodependence and abuse diagnosis. PMID- 17348609 TI - [Metachlorophenylpiperazine (mCPP): a new designer drug]. AB - Metachlorophenylpiperazine (mCPP) is a psychoactive substance that appeared in 2004 on the black market of illicit substances in Europe and France. It has a strong affinity for serotoninergic receptors and the serotonin transporter. In humans, mCPP induces endocrine, neurological and psychiatric effects. Its subjective effects are similar to those of amphetamines. However, drug-users allot few positive subjective effects. Reported cases of intoxication are generally not serious but the risks of psychiatric disorders and serotoninergic syndrome must be taken into account. Risk factors of the intoxication to mCPP are the existence of predisposing psychiatric pathologies and pharmacodynamic or metabolic interactions. mCPP does not exhibit reinforcing effects. mCPP is not the subject of any international regulation: procedures of medical and social risk assessment were implemented in European and the national levels. PMID- 17348610 TI - Manic switch and serotonin syndrome with venlafaxine-lithium-valproate association. PMID- 17348611 TI - [Amisulpride poisoning. A case report]. PMID- 17348612 TI - [Bullous erythema multiform induced by trihexyphenidyl]. PMID- 17348614 TI - [Hyponatremia induced by sodium valproate. A case report]. PMID- 17348613 TI - [Transitory acute psychosis with serotoninergic syndrome at the time of an intoxication by dosulepin associated with doxylamine and ethanol]. PMID- 17348615 TI - [Acute poisoning with oxetorone]. PMID- 17348616 TI - Acute thrombosis of an aortobifemoral graft after cancer surgery and withdrawal of clopidogrel. PMID- 17348617 TI - [Good use of the word "drogue" in French language]. PMID- 17348618 TI - National Audit Office slates DoH over 12m pounds Dr Foster deal. PMID- 17348620 TI - PCT triage plans spark opposition. PMID- 17348619 TI - Government warns PCTs over dentistry capacity. PMID- 17348621 TI - MPs launch contract cleaning probe. PMID- 17348622 TI - Infection control. Germinators look to Europe for the next ideas in superbug war. PMID- 17348623 TI - Sophia Christie. On lessons from Sweden. PMID- 17348624 TI - Whitehall. Come back, bowler brigade, all is forgiven. PMID- 17348625 TI - Data briefing. Cutting emergency admissions. PMID- 17348626 TI - Engaging staff. Talking up the NHS. AB - A negative perception of the NHS by the public runs at odds with the positive feedback of patients. Opinions of the service are coloured by political persuasion, age and people they know who work for it. Other factors for dissent include people feeling that targets are valued more highly than quality of care; and a deep-seated negativity among doctors. PMID- 17348627 TI - Governance. Clinicians under the spotlight. PMID- 17348628 TI - Identification and characterization of small-molecule inducers of epidermal keratinocyte differentiation. AB - An essential function of the human epidermis is the maintenance of a protective barrier against the environment. As a consequence, keratinocytes, which make up this layer of the skin, undergo an elaborate process of self-renewal, terminal differentiation, and cell death. Misregulation of these processes can lead to several human diseases, including psoriasis and basal cell and squamous cell carcinomas. To identify novel regulators of keratinocyte differentiation, a cell based screen of small-molecule libraries was carried out for molecules that induce terminal differentiation of normal human epidermal keratinocytes. One class of molecules was identified, the 2-(3,4,5-trimethoxyphenylamino) pyrrolo[2,3-d]pyrimidines, which were shown to induce differentiation of epidermal progenitor cells to terminally differentiated keratinocytes. These molecules serve as useful mechanistic probes of the cellular differentiation programs that regulate the formation and homeostasis of the epidermis and may lead to novel therapeutic approaches for the treatment of skin hyperproliferative disorders. PMID- 17348629 TI - A minimal peptide sequence that targets fluorescent and functional proteins into the mitochondrial intermembrane space. AB - Protein-based fluorescent and functional probes are widely used for real-time visualization, purification, and regulation of a variety of biological molecules. The protein-based probes can generally be targeted into subcellular compartments of eukaryotic cells by a particular short peptide sequence. Little is known, however, about the sequence that targets probes into the mitochondrial intermembrane space (IMS). To identify the IMS-targeting sequence, we developed a simple genetic screening method to discriminate the proteins localized in the IMS from those in the mitochondrial matrix, thereby revealing the minimum requisite sequence for the IMS targeting. An IMS-localized protein, Smac/DIABLO, was randomly mutated, and the mitochondrial localization of each mutant was analyzed. We found that the four residues of Ala-Val-Pro-Ile are required for IMS localization, and a sequence of these four residues fused with matrix-targeting signals is sufficient for targeting the Smac/DIABLO into the IMS. The sequence was shown to readily direct three dissimilar proteins of interest to the IMS, which will open avenues to elucidating the functions of the IMS in live cells. PMID- 17348630 TI - Efficient surface patterning of oligonucleotides inside a glass capillary through oxime bond formation. AB - The efficient surface patterning of oligonucleotides was accomplished onto the inner wall of fused-silica capillary tubes as well as on the surface of glass slides through oxime bond formation. The robustness of the method was demonstrated by achieving the surface immobilization of up to three different oligonucleotide sequences inside the same capillary tube. The method involves the preparation of surfaces grafted with reactive aminooxy functionalities masked with the photocleavable protecting group, 2-(2-nitrophenyl) propyloxycarbonyl group (NPPOC). Briefly, NPPOC-aminooxy silane 1 was prepared and used to silanize the glass surfaces. The NPPOC group was cleaved under brief irradiation to unmask the reactive aminooxy group on surfaces. These reactive aminooxy groups were allowed to react with aldehyde-containing oligonucleotides to achieve an efficient surface immobilization. The advantage associated with the present approach is that it combines the high-coupling efficiency of oxime bond formation with the convenience associated with the use of photolabile groups. The present strategy thus offers an alternative approach for the immobilization of biomolecules in the microchannels of "labs on a chip" devices. PMID- 17348631 TI - Online concentration and affinity separation of biomolecules using multifunctional particles in capillary electrophoresis under magnetic field. AB - To overcome several problems in affinity capillary electrophoresis (ACE), i.e., low detectability, need for sample derivatization, and difficulty in the fixation of affinity ligands (ALs), multifunctional magnetic particles (MFMPs) were prepared by immobilizing both fluorescent molecules and ALs for low-density lipoproteins onto the surface of magnetic polymer microspheres with a polyelectrolyte multilayer coating technique and applied to the ACE analysis. The prepared MFMPs showed a remarkable change in the electrophoretic mobility (mu ep) by the addition of low-density lipoproteins (LDL), whereas for high-density lipoproteins (HDL), mu ep of the MFMPs kept constant, so that it was confirmed that the MFMPs possess an affinity with LDL. On the other hand, the MFMPs can be trapped by the magnetic field even under a higher electric field for electrophoresis. By a successive on-off control of the magnetic field, online preconcentration of the LDL bound MFMPs and the selective separation of LDL from HDL were successfully achieved. In the ACE analysis of LDL employing UV detection, an 82-fold increase in the sensitivity was obtained by the on capillary sample preconcentration using the MFMPs. When laser induced fluorescence detection was employed, furthermore, the limit of detection for LDL was improved to the order of subpicomolar. PMID- 17348632 TI - Simplification of mass spectral analysis of acidic glycopeptides using GlycoPep ID. AB - Mass spectral analysis is an increasingly common method used to characterize glycoproteins. When more than one glycosylation site is present on a protein, obtaining MS data of glycopeptides is a highly effective way of obtaining glycosylation information because this approach can be used to identify not only what the carbohydrates are but also at which glycosylation site they are attached. Unfortunately, this is not yet a routine analytical approach, in part because data analysis can be quite challenging. We are developing strategies to simplify this analysis. Presented herein is a novel mass spectrometry technique that identifies the peptide moiety of either sulfated, sialylated, or both sialylated and sulfated glycopeptides. This technique correlates product ions in collision-induced dissociation (CID) experiments of suspected glycopeptides to a peptide composition using a newly developed web-based tool, GlycoPep ID. After identifying the peptide portion of glycopeptides with GlycoPep ID, the process of assigning the rest of the glycopeptide composition to the MS data is greatly facilitated because the "unknown" portion of the mass assignment that remains can be directly attributed to the carbohydrate component. Several examples of the utility and reliability of this method are presented herein. PMID- 17348633 TI - Aptamer-conjugated nanoparticles for the collection and detection of multiple cancer cells. AB - We have extended the use the aptamer-conjugated nanoparticles for the collection and detection of multiple cancer cells. The aptamers were selected using a cell based SELEX strategy in our laboratory for cancer cells that, when utilized in this method, allow for the selective recognition of the cells from complex mixtures including fetal bovine serum samples. Aptamer-conjugated magnetic nanoparticles were used for the selective targeting cell extraction, and aptamer conjugated fluorescent nanoparticles were employed for sensitive cellular detection. Employing both types of nanoparticles allows for selective and sensitive detection not possible by using the particles separately. Fluorescent nanoparticles amplify the signal intensity versus a single fluorophore label resulting in improved sensitivity. In addition, aptamer-conjugated magnetic nanoparticles allow for extraction and enrichment of target cells not possible with other separation methods. Fluorescent imaging and a microplate reader were used for cellular detection to demonstrate the wide applicability of this methodology for medical diagnostics and cell enrichment and separation. PMID- 17348634 TI - Comprehensive two-dimensional field-flow fractionation-liquid chromatography in the analysis of large molecules. AB - A novel, comprehensive two-dimensional asymmetric field-flow fractionation-liquid chromatographic system is described (AsFlFFF-RPLC). The interface is based on a switching valve, and the whole sample is analyzed in both dimensions. The system proved to be repeatable and quantitative in the characterization of egg white proteins. Four peaks at 4, 5.5-6.0, 7.5-8.0, and 10.0-11.0 nm, and corresponding to lysozyme, ovalbumin, transferrin, and a dimer of transferrin, were obtained in the AsFlFFF first-dimension system. Lysozyme also produced an additional peak, which overlapped with ovalbumin. Twelve compounds were separated in the LC second dimension system. Identifications were made with the help of standards (ovalbumin, ovotransferrin, lysozyme) and by comparison of the peak areas, particle sizes, and retention data with values given in the literature. The effect of heat on egg white denaturation was studied, and the unfolding of peptide bonds of the protein was found to be pronounced when the sample was heated in phosphate solution. PMID- 17348635 TI - Analysis of pharmaceuticals in fish using liquid chromatography-tandem mass spectrometry. AB - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening method has been developed targeting 23 pharmaceuticals and 2 metabolites with differing physicochemical properties in fish tissue. Reversed-phase separation of target compounds was achieved using a C18 column and a nonlinear gradient consisting of 0.1% (v/v) formic acid and methanol. Eluted analytes were introduced into the mass analyzer using positive or negative electrospray ionization, as appropriate. A variety of extraction solvents, differing in polarity, pH, or both, were investigated in order to assess recovery of target compounds from 1-g tissue homogenates. Among 10 solvents tested, a 1:1 mixture of 0.1 M aqueous acetic acid (pH 4) and methanol was identified as optimal, resulting in extraction recoveries for 24 of 25 compounds exceeding 60%. Tissue extracts were found to influence the LC-MS/MS response for several analytes. Consequently, matrix-matched calibration standards were employed to determine analyte concentrations in environmental samples. Statistically derived method detection limits were <6 ng/g for most analytes. The method was subsequently used to screen for target analytes in fish from an effluent-dominated stream. Diphenhydramine, diltiazem, carbamazepine, and norfluoxetine were detected in 11 of 11 environmental samples at concentrations ranging from 0.11 to 5.14 ng/g. PMID- 17348636 TI - Driving forces in the delivery of penetratin conjugated G protein fragment. AB - A42 is a chimera peptide consisting of Galphas(374-394)C379A--the 21-mer C terminus of the Galphas protein, able of adenosine inhibitory activity--and penetratin--the 16 residue fragment, derived from the homeodomain of the Drosophila transcription factor Antennapedia. A42 is able to cross cell membranes and to inhibit A2A and A2B adenosine and beta-adrenergic receptor stimulated camps (D'Ursi et al. Mol. Pharmacol. 2006, 69, 727-36). Here we present an extensive biophysical study of A42 in different membrane mimetics, with the objective to evaluate the molecular mechanisms which promote the membrane permeation. Fluorescence, CD, and NMR data were acquired in the presence of negatively charged and zwitterionic sodium dodecyl sulfate and dodecylphosphocholine surfactants. To validate the spectroscopic results in a larger scale, fluorescence microscopy experiments were performed on negatively charged and zwitterionic dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylcholine vesicles. Our results show that the internalization of A42 is mainly driven by electrostatic interactions, hydrophobic interactions playing only a secondary, sinergistic role. The distribution of the charges along the molecule has an important role, highlighting that internalization is a process which requires a specific matching of peptide and membrane properties. PMID- 17348637 TI - Cinnamoyl compounds as simple molecules that inhibit p300 histone acetyltransferase. AB - Cinnamoly compounds 1a-c and 2a-d were designed, synthesized, and in vitro tested as p300 inhibitors. At different degrees, all tested compounds were proven to inactivate p300, particularly, derivative 2c was the most active inhibitor, also showing high specificity for p300 as compared to other histone acetyltransferases. Most notably, 2c showed anti-acetylase activity in mammalian cells. These compounds represent a new class of synthetic inhibitors of p300, characterized by simple chemical structures. PMID- 17348638 TI - Synthesis and pharmacological characterization of N3-substituted willardiine derivatives: role of the substituent at the 5-position of the uracil ring in the development of highly potent and selective GLUK5 kainate receptor antagonists. AB - Some N3-substituted analogues of willardiine such as 11 and 13 are selective kainate receptor antagonists. In an attempt to improve the potency and selectivity for kainate receptors, a range of analogues of 11 and 13 were synthesized with 5-substituents on the uracil ring. An X-ray crystal structure of the 5-methyl analogue of 13 bound to GLUK5 revealed that there was allowed volume around the 4- and 5-positions of the thiophene ring, and therefore the 4,5 dibromo and 5-phenyl (67) analogues were synthesized. Compound 67 (ACET) demonstrated low nanomolar antagonist potency on native and recombinant GLUK5 containing kainate receptors (KB values of 7 +/- 1 and 5 +/- 1 nM for antagonism of recombinant human GLUK5 and GLUK5/GLUK2, respectively) but displayed IC50 values >100 microM for antagonism of GLUA2, GLUK6, or GLUK6/GLUK2. PMID- 17348639 TI - Synthesis and anti-cancer activity of C-ring-functionalized prodigiosin analogues. AB - Prodigiosin is the parent member of the 4-methoxypyrrolyldipyrromethene family of natural products and is known for its anti-cancer activity. A new series of analogues was synthesized, incorporating pendent functional esters and beta carbonyl substituents on the C-ring. The beta-carbonyl group allowed for the facile isolation of the prodigiosenes, and the pendent esters allow for further derivatization. The novel prodigiosenes generally retain the anti-cancer activity of prodigiosin in 60 human cell lines derived from nine cancer cell types, with neither the conjugated beta-carbonyl group, as either ketone or ester, nor the pendent ester significantly reducing the anti-cancer activity of the core skeleton. PMID- 17348640 TI - Peripheral and axial substitution of phthalocyanines with solketal groups: synthesis and in vitro evaluation for photodynamic therapy. AB - Phthalocyanines (Pcs) are a class of photosensitizers (PSs) with a strong tendency to aggregate in aqueous environment, which has a negative influence on their photosensitizing ability in photodynamic therapy. Pcs with either peripheral or axial solketal substituents, that is, ZnPc(sol)8 and Si(sol)2Pc, respectively, were synthesized and their tendency to aggregate as well as their photodynamic properties in 14C and B16F10 cell lines were evaluated. The results were compared to more hydrophilic silicon Pcs, that is, Si(PEG750)2Pc and Pc4. The order of cellular uptake was Pc4 > ZnPc(sol)8 > Si(PEG750)2Pc > Si(sol2)Pc. In contrast, Si(sol2)Pc showed the highest photocytotoxicity, while ZnPc(sol)8 did not show any photocytotoxicity up to a concentration of 10 microM in both cell types. UV/vis spectroscopy showed that Si(sol)2Pc is less prone to aggregation than ZnPc(sol)8, which can explain the lack of photoactivity of the latter. Si(sol)2Pc was predominantly located in lipid droplets, whereas Si(PEG750)2Pc was homogeneously distributed in the cytosol, which is probably the main cause of their difference in photoactivity. The very high photodynamic efficacy of Si(sol)2Pc makes this PS an interesting candidate for future studies. PMID- 17348641 TI - New copper and silver trimethylsilylchalcogenolates. AB - The synthesis and characterization of the copper and silver trimethylsilylchalcogenolates (EtPh2P)3MESiMe3 and (Et2PhP)3MESiMe3 (M = CuI, AgI) are reported. These chalcogenolate complexes can be prepared in high yield; however, they are thermally unstable. Low-temperature single-crystal X-ray analysis of (EtPh2P)3CuSSiMe3 (1b) and (Et2PhP)3CuSeSiMe3 (2a) confirms the terminal coordination of the chalcogen ligand and the tetrahedral coordination about the metal. Protonolysis of 2a with EtOH yields the terminal selenol complex (Et2PhP)3CuSeH (6). Reaction of 1b with EtPh2P-solubilized AgOAc yields the heterometallic cluster [Cu9Ag3S6(PEtPh2)8] (7) in good yield. PMID- 17348642 TI - On the relevance of an antiferromagnetic dimer model for the spin-gapped magnetic solids Cu(terpy)Mo2O7 and Cu(OH)(p-pyc)H2O. AB - The magnetic solids Cu(terpy)Mo2O7 (terpy = terpyridine) and Cu(OH)(p-pyc)H2O (p pyc = p-pyridinecarboxylate) have a spin gap and possess chains of Cu2+ ions in which two different Cu...Cu distances alternate. On the basis of their reported crystal structures, the spin-exchange interactions of these compounds were examined by performing spin dimer analysis to determine whether an antiferromagnetic dimer or an alternating antiferromagnetic chain model is appropriate for their magnetic properties. Our analysis shows that an antiferromagnetic dimer model is correct for both compounds because of the anisotropic overlap between the magnetic orbitals of their Cu2+ sites. PMID- 17348643 TI - Structure and physical properties of the polar oxysulfide CaZnOS. AB - The synthesis, structure, and electrical properties of the oxysulfide CaZnOS are reported. The white compound has a band gap of 3.7(1) eV and crystallizes in hexagonal space group P6(3)mc (No. 186) with a = 3.75726(3) A, c = 11.4013(1) A, and Z = 2. The noncentrosymmetric structure, which has few analogues, is composed of isotypic puckered hexagonal ZnS and CaO layers arranged so that ZnS3O tetrahedra are all aligned parallel, resulting in a polar structure. The compound shows type 1 non-phase-matchable second harmonic generation, determined using 1064 nm radiation, with an efficiency approximately 100 times that of alpha-SiO2 and a piezoelectric coefficient of 38 pm V-1. Although polar, CaZnOS is not ferroelectric and the pyroelectric coefficient is very small, approximately 0.0 microC m-2 K-1 between room temperature and 100 degrees C. PMID- 17348644 TI - Two-photon antenna effect induced in octupolar europium complexes. AB - The synthesis of new chromophore-based pyridine-dicarboxamide ligands and related D3 symmetric europium(III) complexes is described. The photophysical properties of the ligands and the complexes were thoroughly investigated and interpreted on the basis of theoretical calculations (TD-DFT). Finally, the luminescence of Eu(III) was sensitized by two-photon absorption of the ligand, illustrating the two-photon antenna effect phenomenon. PMID- 17348645 TI - Effect of the metal environment on the ferromagnetic interaction in the Co-NC-W pairs of octacyanotungstate(V)-Cobalt(II) three-dimensional networks. AB - State of the art CASSCF and CASPT2 calculations have been performed to elucidate the nature of ferromagnetism of CoII-NC-WV pairs in the three-dimensional compound [[WV(CN)2]2[(micro-CN)4CoII(H2O)2]3.4H2O]n, which has been recently synthesized and investigated by a number of experimental techniques (Herrera, J. M.; Bleuzen, A.; Dromzee, Y.; Julve, M.; Lloret, F.; Verdaguer, M. Inorg. Chem. 2003, 42, 7052-7059). In this network, the Co ions are in the high-spin (S = 3/2) state, while the single unpaired electron on the W centers occupies the lowest orbital of the dz2 type of the 5d shell. In agreement with the suggestion made by Herrera et al., we find that the ferromagnetism is due to a certain occupation scheme of the orbitals from the parent octahedral t2g shell on CoII sites, in which the orbital accommodating the unpaired electron is orthogonal to the dz2 orbitals of the surrounding W ions. We investigate the stabilization of such an orbital configuration on the Co sites and find that it cannot be achieved in the ground state of isolated mononuclear fragments [CoII(NC)4(OH2)2]2- for any conformations of the coordinated water molecules and Co-N-C bond angles. On the other hand, it is stabilized by the interaction of the complex with neighboring W ions, which are simulated here by effective potentials. The calculated exchange coupling constants for the CoII-NC-WV binuclear fragments are in reasonable agreement with the measured Curie-Weiss constant for this compound. As additional evidence for the inferred electronic configuration on the Co sites, the ligand field transitions, the temperature-dependent magnetic susceptibility, and the field-dependent low-temperature magnetization, simulated ab initio for the mononuclear Co fragments, are in agreement with the available data for another compound [WIV[(micro-CN)4-CoII(H2O)2]2.4H2O]n containing diamagnetic W and high spin Co ions in an isostructural environment. PMID- 17348646 TI - Construction of robust open metal-organic frameworks with chiral channels and permanent porosity. AB - Four new metal-organic frameworks (MOFs) containing chiral channels have been synthesized using an achiral, triazine-based trigonal-planar ligand, 4,4',4' '-s triazine-2,4,6-triyltribenzoate (TATB), and an hourglass secondary building unit (SBU): Zn3(TATB)2(H2O)2.4DMF.6H2O (1); Cd3(TATB)2(H2O)2.7DMA.10H2O (2); [H2N(CH3)2][Zn3(TATB)2(HCOO)].HN(CH3)2.3DMF.3H2O (3); [H2N(CH3)2][Cd3(TATB)2(CH3COO)].HN(CH3)2.3DMA.4H2O (4). MOFs 1 and 2 are isostructural and possess (10,3)-a nets containing large chiral channels of 20.93 and 21.23 A, respectively, but are thermally unstable due to the easy removal of coordinated water molecules on the SBU. Replacement of these water molecules by formate or acetate generated in situ leads to 3 and 4, respectively. Formate or acetate links SBUs to form infinite helical chains bridged by TATB to create three-dimensional anionic networks, in which one of the two oxygen atoms of the formate or acetate is uncoordinated and points into the void of the channels. This novel SBU-stabilization and channel-functionalization strategy may have general implications in the preparation of new MOFs. Thermogravimetric analysis (TGA) shows that solvent-free 3' is thermally stable to 410 degrees C, while TGA studies on samples vapor-diffused with water, methanol, and chloroform show reversible adsorption. MOF 3 also has permanent porosity with a large Langmuir surface area of 1558 m2/g. All complexes exhibit similar strong luminescence with a lambdamax of approximately 423 nm upon excitation at 268.5 nm. PMID- 17348647 TI - Carboranes and baskets from reaction of B4H10 with allene. AB - The reaction of the boron hydride B4H10 with allene was studied at the CCSD(T)/6 311+G(d)//MP2/6-31G(d) level. The mechanism is surprisingly complex with 44 transition states and several branching points located. The four carboranes and one basket that have been observed experimentally are all connected by pathways that have very similar free energies of activation. In addition, two new structures, a basket (2,4-(CH2CH2CH2)B4H8, 5a) and a "classical" structure (1,4 (Me2C)bisdiborane, 7), which might be obtained from the B4H10 + C3H4 reaction under the right conditions (hot/cold, quenched, etc.) have been identified. The first branch point in the reaction is the competition between H2 elimination from B4H10 (DeltaG(298 K) = 32.2 kcal/mol) and the hydroboration of allene by B4H10 (DeltaG(298 K) = 31.3 kcal/mol). The next branch point in the hydroboration mechanism controls the formation of 2,4-(MeCHCH2)B4H8 (1) (DeltaG(298 K) = 31.5 kcal/mol) and arachno-1,2/arachno-1,3-Me2-1-CB4H7 (8 and 8a) (DeltaG(298 K) = 34.3 kcal/mol). Another branch point in the H2-elimination mechanism controls the formation of 1-Me-2,5-micro-CH2-1-CB4H7 (29) (DeltaG(298 K) = 0.1 kcal/mol) and 2,5-micro-CHMe-1-CB4H7 (25/26) (DeltaG(298 K) = 7.3 kcal/mol). Formation of 2-Me 2,3-C2B4H7, a carborane observed in the reaction of methylacetylene with B4H10, is calculated to be blocked by a high barrier for H2 elimination. All free energies are relative to B4H10 + allene. An interesting reaction step discovered is the "reverse hydroboration step" in which a hydrogen atom is transferred from carbon back to boron, which allows a CH hydrogen to shuttle between the terminal and central carbon of allene. PMID- 17348648 TI - Structure-activity correlation in titanium single-site olefin polymerization catalysts containing mixed cyclopentadienyl/aryloxide ligation. PMID- 17348649 TI - Tetrasubstituted pyrrolidines via a tandem aza-Payne/hydroamination reaction. PMID- 17348650 TI - Benzil-tethered precipitons for controlling solubility: a round-trip energy transfer mechanism in the isomerization of extended stilbene analogues. AB - We are investigating photoresponsive molecules called "precipitons" that undergo a solubility change co-incident with isomerization. Isomerization can be induced by light or by catalytic reagents. Previous work demonstrated that covalent attachment of a metal complex, Ru(II)(bpy)3, greatly accelerates photoisomerization and influences the photostationary state. In this paper, we describe precipitons (1,2-biphenylethenes; analogous to stilbenes) that are activated by a covalently attached organic sensitizer (benzil). We find that isomerization of these stilbene analogues is little effected by the presence of benzil in solution but that the intramolecular benzil effect is to increase the rate of isomerization and to significantly change the photostationary state. What is most interesting about these observations is that the precipiton is the primary chromophore in this bichromophoric system (precipiton absorbance is many times greater than benzil absorbance in the 300-400 nm range), yet the neighboring benzil has a significant effect on the rate and the photostationary state. The effect of unattached benzil on the rate was small, about a 24% increase in rate as compared with 4-6-fold changes for an attached benzil. We speculate that the isomerization process occurs by a "round-trip" energy-transfer mechanism. Initial excitation of the precipiton chromophore initiates a sequence that includes (1) formation of the precipiton singlet state, (2) singlet excitation transfer from the precipiton unit to the benzil, (3) benzil-centered intersystem crossing to the localized benzil triplet state, (4) triplet energy transfer from the benzil moiety back to the precipiton, and (5) isomerization. PMID- 17348651 TI - Ester versus polyketone formation in the palladium-diphosphine catalyzed carbonylation of ethene. AB - The origin of the chemoselectivity of palladium catalysts containing bidentate phosphine ligands toward either methoxycarbonylation of ethene or the copolymerization of ethene and carbon monoxide was investigated using density functional theory based calculations. For a palladium catalyst containing the electron-donating bis(dimethylphosphino)ethane (dmpe) ligand, the rate determining step for chain propagation is shown to be the insertion of ethene into the metal-acyl bond. The high barrier for chain propagation is attributed to the low stability of the ethene intermediate, (dmpe)Pd(ethene)(C(O)CH3). For the competing methanolysis process, the most likely pathway involves the formation of (dmpe)Pd(CH3OH)(C(O)CH3) via dissociative ligand exchange, followed by a solvent mediated proton-transfer/reductive- elimination process. The overall barrier for this process is higher than the barrier for ethene insertion into the palladium acetyl bond, in line with the experimentally observed preference of this type of catalyst toward the formation of polyketone. Electronic bite angle effects on the rates of ethene insertion and ethanoyl methanolysis were evaluated using four electronically and sterically related ligands (Me)2P(CH2)nP(Me)2 (n = 1-4). Steric effects were studied for larger tert-butyl substituted ligands using a QM/MM methodology. The results show that ethene coordination to the metal center and subsequent insertion into the palladium-ethanoyl bond are disfavored by the addition of steric bulk around the metal center. Key intermediates in the methanolysis mechanism, on the other hand, are stabilized because of electronic effects caused by increasing the bite angle of the diphosphine ligand. The combined effects explain successfully which ligands give polymer and which ones give methyl propionate as the major products of the reaction. PMID- 17348652 TI - Intermolecular chain-to-chain tunneling in metal-alkanethiol-metal junctions. PMID- 17348653 TI - Hybrid peptide design. Hydrogen bonded conformations in peptides containing the stereochemically constrained gamma-amino acid residue, gabapentin. AB - The crystal structure of 12 peptides containing the conformationally constrained 1-(aminomethyl)cyclohexaneacetic acid, gabapentin (Gpn), are reported. In all the 39 Gpn residues conformationally characterized so far, the torsion angles about the Calpha-Cbeta and Cbeta-Cgamma bonds are restricted to the gauche conformation (+/-60 degrees ). The Gpn residue is constrained to adopt folded conformations resulting in the formation of intramolecularly hydrogen-bonded structures even in short peptides. The peptides Boc-Ac6c-Gpn-OMe 1 and Boc-Gpn-Aib-Gpn-Aib-OMe 2 provide examples of C7 conformation; peptides Boc-Gpn-Aib-OH 3, Boc-Ac6c-Gpn-OH 4, Boc-Val-Pro-Gpn-OH 5, Piv-Pro-Gpn-Val-OMe 6, and Boc-Gpn-Gpn-Leu-OMe 7 provide examples of C9 conformation; peptide Boc-Ala-Aib-Gpn-Aib-Ala-OMe 8 provides an example of C12 conformation and peptides Boc-betaLeu-Gpn-Val-OMe 9 and Boc betaPhe-Gpn-Phe-OMe 10 provide examples of C13 conformation. Gpn peptides provide examples of backbone expanded mimetics for canonical alpha-peptide turns like the gamma (C7) and the beta (C10) turns. The hybrid betagamma sequences provide an example of a mimetic of the C13 alpha-turn formed by three contiguous alpha-amino acid residues. Two examples of folded tripeptide structures, Boc-Gpn-betaPhe-Leu OMe 11 and Boc-Aib-Gpn-betaPhg-NHMe 12, lacking internal hydrogen bonds are also presented. An analysis of available Gpn residue conformations provides the basis for future design of folded hybrid peptides. PMID- 17348654 TI - A new route for the synthesis of uniform nanozeolites with hydrophobic external surface in organic solvent medium. PMID- 17348655 TI - Cation-anion interactions as structure directing factors: structure and bonding of Ca2CdSb2 and Yb2CdSb2. AB - Two new transition-metal-containing Zintl phases, Ca2CdSb2 and Yb2CdSb2, have been synthesized by flux reactions, and their structures have been determined by single-crystal X-ray diffraction. Yb2CdSb2 crystallizes in the noncentrosymmetric orthorhombic space group Cmc21 (No. 36, Z = 4). Ca2CdSb2 crystallizes in the centrosymmetric orthorhombic space group Pnma (No. 62, Z = 4). Despite the similarity in their chemical formulas and unit cell parameters, the structures of Yb2CdSb2 and Ca2CdSb2 are subtly different: Ca2CdSb2 has a layered structure built up of infinite layers of CdSb4 tetrahedra connected through corner-sharing. These layers are stacked in an alternating AA-1AA-1 sequence along the direction of the longest crystallographic axis (A denotes a layer; A-1 stands for its inversion symmetry equivalent), with Ca2+ cations filling the space between them. The structure of Yb2CdSb2 features the very same [CdSb2]4- layers of CdSb4 tetrahedra, which because of the lack of inversion symmetry are stacked in an AAAA-type fashion and are separated by Yb2+ cations. Electronic band structure calculations performed using the TB-LMTO-ASA method show a small band gap at the Fermi level for Ca2CdSb2, whereas the gap closes for Yb2CdSb2. These results suggest narrow gap semiconducting and poorly metallic behavior, respectively, and are confirmed by resistivity and magnetic susceptibility measurements. The structural relationship between these new layered structure types and some well known structures with three-dimensional four-connected nets are discussed as well. PMID- 17348656 TI - Pyrophosphate-selective fluorescent chemosensor at physiological pH: formation of a unique excimer upon addition of pyrophosphate. PMID- 17348657 TI - Solid-state self-assembly of a calix[4]pyrrole-resorcinarene hybrid into a hexameric cage. PMID- 17348658 TI - Circumventing anti-androgen resistance by molecular design. PMID- 17348659 TI - Catalytic enantioselective synthesis of flavanones and chromanones. PMID- 17348660 TI - Aggregation of rod-coil block copolymers containing rigid polyampholyte blocks in aqueous solution. PMID- 17348661 TI - A double concave hydrocarbon buckycatcher. PMID- 17348662 TI - Rhodium-catalyzed intramolecular alkyne-carbodiimide Pauson-Khand-type reaction. AB - [structure: see text]. An efficient, Rh-catalyzed intramolecular Pauson-Khand type carbonylation of alkyne-carbodiimides leading to 4,5-dihydro-1H-pyrrolo[2,3 b]pyrrolin-2-ones and 1H-pyrrolo[2,3-b]indol-2-ones is described. PMID- 17348663 TI - Novel formal synthesis of cephalotaxine via a facile Friedel-Crafts cyclization. AB - [structure: see text]. A novel formal synthesis of cephalotaxine (CET), the parent structure of the antileukemia Cephalotaxus alkaloids, was achieved via a facile Friedel-Crafts cyclization of the amino (or amido) spiro-cyclopentenone precursor (A) mediated by a protic acid leading to tetracyclic ketone B. A remarkable stereoelectronic effect of the methylenedioxy substituent (R) and an interesting skeletal isomerization of the CET core ring system (B, X = H2) were observed. PMID- 17348664 TI - Regio- and stereoselective copper-catalyzed carbozincation reactions of alkynyl sulfoximines and sulfones. AB - [structure: see text]. Stereochemically pure polysubstituted vinyl sulfoximines and sulfones are easily prepared by a copper-catalyzed syn carbozincation reaction of the corresponding alkynyl derivatives. PMID- 17348665 TI - Rapid and efficient microwave-assisted copper(0)-catalyzed ullmann coupling reaction: general access to anilinoanthraquinone derivatives. AB - [structure: see text]. The synthesis of anilinoanthraquinones 3a-z was achieved by a new, Cu(0)-catalyzed, microwave-assisted Ullmann coupling reaction of bromaminic acid (1) with aniline derivatives 2a-z in phosphate buffer. Good to excellent isolated yields were obtained within only 2-20 min at 80-120 degrees C and 40-100 W. The new procedure provides the first general access to anilinoanthraquinones, furnishing a number of previously inaccessible compounds. It is superior to classical methods in all aspects, including yields, reaction time, and versatility. PMID- 17348666 TI - The first enantioenriched metalated nitrile possessing macroscopic configurational stability. AB - [structure: see text]. Magnesium-bromine exchange on enantiopure cyclopropyl bromonitrile 5 at -100 degrees C for 1 min followed by a D2O quench gives the deuterionitrile in 81% ee (retention); additional trapping experiments establish t(1/2)(rac) = 11.4 h at -100 degrees C. These experiments provide the first glimpse into the stereochemical aspects of Mg-Br exchange. The intermediate formed is the first metalated nitrile demonstrated to possess macroscopic configurational stability. PMID- 17348667 TI - PhI(OAc)2 -mediated novel 1,3-dipolar cycloaddition of methylenecyclopropanes (MCPs), vinylidenecyclopropanes (VCPs), and methylenecyclobutane (MCB) with phthalhydrazide. AB - [structure: see text]. Iodobenzene diacetate-mediated reactions of methylenecyclopropanes 1, vinylidenecyclopropanes 2, and a methylenecyclobutane 3a with phthalhydrazide give the corresponding [3+2] cycloaddition products in good yields under mild conditions. In these reactions, phthalhydrazide was transformed to a 1,3-dipole intermediate in the presence of iodobenzene diacetate. A plausible reaction mechanism has been proposed. PMID- 17348668 TI - Regiospecific organocatalytic asymmetric aldol reaction of methyl ketones and alpha,beta-unsaturated trifluoromethyl ketones. AB - [structure: see text]. The aldol reaction of methyl ketones and alpha,beta unsaturated trifluoromethyl ketones occurred under mild conditions with the combination of proline-derived N-sulfonylamide and trifluoroacetic acid as the catalyst to give the corresponding unsaturated alpha-trifluoromethyl tertiary alcohols in high yields with good enatioselectivities. PMID- 17348669 TI - A novel highly stereoselective synthesis of 2,3-disubstituted 3H-quinazoline-4 one derivatives. AB - [structure: see text]. An efficient three-step synthesis of chiral 3H-quinazoline 4-one derivatives from commercial materials is disclosed. The Mumm reaction of imidoyl chloride with alpha-amino acids followed by reductive cyclization affords enantiomerically pure (ee >93%) quinazoline-4-ones in good overall yield. A comparison with existing approaches indicates that this method is superior for hindered substrates. PMID- 17348670 TI - Effect of storage conditions on the biological activity of phenolic compounds of blueberry extract packed in glass bottles. AB - Recent research suggests that blueberries are rich in total polyphenols and total anthocyanins. Phenolic compounds are highly unstable and may be lost during processing, particularly when heat treatment is involved. There is no systematic study available providing information on the fate of phenolic compounds during storage and how that affects their biological activity. We provide a systematic evaluation of the changes observed in total polyphenols (TPP), total anthocyanins (TACY), Trolox equivalent antioxidant capacity (TEAC), phenolic acids, and individual anthocyanins of blueberry extract stored in glass bottles and the ability of blueberry extract to inhibit cell proliferation. The extract was stored at different temperatures (-20 +/- 1, 6 +/- 1, 23 +/- 1, and 35 +/- 1 degrees C). Two cultivars, Tifblue and Powderblue, were chosen for the study. The recoveries of TPP, TACY, and TEAC in blueberry extract after pressing and heating were approximately 25, approximately 29, and approximately 69%, respectively, for both cultivars. The recovery of gallic acid, catechin, and quercetin was approximately 25%. Ferulic acid was not detected in the final extract in both Tifblue and Powderblue cultivars. The recovery of peonidin, malvidin, and cyanidin glycosides was approximately 20% in the final extract in both cultivars. Losses due to storage were less when compared with initial losses due to processing. At -20 degrees C, no statistically significant loss of TPP, TACY, and TEAC was observed up to 30 days (P < 0.05). At 6 degrees C storage, there was a significant loss observed from 15 to 30 days. Similar results were obtained at 23 and 35 degrees C (P < 0.05). There was retention of more than 40% of ellagic and quercetin after 60 days at 35 +/- 1 degrees C. Anthocyanins were not detected after 60 days of storage at 35 +/- 1 degrees C. Significant retention (P < 0.05) was obtained for malvidin (42.8 and 25.8%) and peonidin (74.0 and 79.5%) after 60 days of storage at 23 +/- 1 degrees C in glass bottles for Tifblue and Powderblue, respectively, when compared with other individual anthocyanins. A linear relationship was observed between TEAC values and total polyphenols or total anthocyanins. A cell viability assay was performed using HT-29 cancer cell lines and anthocyanins extracted from 30, 60, and 90 days of stored extract at 6 +/- 1 and 23 +/- 1 degrees C. A significant cell proliferation inhibition percentage was observed in 30 days, although this was reduced significantly after 30-90 days. These results suggest that heating and storage conditions significantly affect the phenolic compounds and their biological activities. Frozen and low temperature storage are suggested for blueberry extract in order to retain the bioactive components. PMID- 17348671 TI - Detection of sialylated phosphorylated kappa-casein glycomacropeptide electrophoresed on polyacrylamide gels and cellulose acetate strips by the thiobarbituric acid and malachite green dye reactions. AB - A 64 amino acid residue sialylated phosphorylated glycomacropeptide (GMP) from bovine sweet whey can be detected as a Coomassie blue-staining peptide by electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gels. There is, however, limited information available concerning detection of GMP as a sialylated phosphorylated compound. Samples of GMP were electrophoresed on SDS polyacrylamide gels or cellulose acetate strips (CAS). Immediately following electrophoresis, fractions obtained by cutting gels or strips were subjected to sialic acid determination by the thiobarbituric acid reaction and phosphorus determination by the malachite green dye reaction. Both determinations were found to be sensitive enough to detect approximately 20 and 40 microg of GMP in CAS and SDS gels, respectively. Further studies demonstrated that sialylated phosphorylated GMP can be detected on either SDS gels or CAS loaded with whey products or whey-added margarine residues. PMID- 17348672 TI - Diverted secondary metabolism and improved resistance to European corn borer (Ostrinia nubilalis) in maize (Zea mays L.) transformed with wheat oxalate oxidase. AB - An alteration in the secondary metabolism of maize (Zea mays L.) genetically modified with the wheat oxalate oxidase (OxO) gene was observed using HPLC and fluorescence microscopy. Phenolic concentrations in the OxO lines were significantly increased, but DIMBOA synthesis was reduced due to a diversion in the shikimate pathway leading to phenolic and hydroxamic acids. Ferulic acid exhibited the largest increase and accounted for 80.4% of the total soluble phenolics. Transcription of a 13-lipoxygenase gene, coding for a key enzyme involved in the regulation of secondary metabolism, was substantially higher in the OxO line than in the null line. To test whether the high levels of soluble phenolic acids, in particular ferulic acid, contributed to the insect resistance in the OxO maize, ferulic acid was administered in meridic diets to European corn borer (ECB). A significant negative correlation between ferulic acid concentration and ECB larval growth rate was found. Field testing during 2001 showed that OxO maize was more resistant to ECB, with leaf consumption and stalk tunneling damage significantly reduced by 28-34 and 37-39%, respectively, on all of the OxO lines tested and confirming published 2000 findings. PMID- 17348673 TI - A new process for the management of olive oil mill waste water and recovery of natural antioxidants. AB - The high polyphenol content of the wastewater is the major environmental problem caused by the olive mills. A pilot scale system for the treatment of the olive oil mills wastewater was developed aiming at the recovery of high added value contained polyphenols and the reduction of the environmental problems. The treatment system consists of three main successive sections: The first one includes successive filtration stages aiming at the gradual reduction of the wastewater suspended solids up to a limit of 25 microm. The second section includes passing of the filtered wastewater through a series of adsorbent resins (XAD16 and XAD7HP) in order to achieve the de-odoring and decolorization of the wastewater and the removal/ recovery of the polyphenol and lactone content. The third section of the procedure includes the thermal evaporation and recovery of the organic solvents mixture, which has been used in the resin regeneration process, and finally the separation of the polyphenols and other organic substance contents using fast centrifuge partition chromatography. The final outcome of the whole procedure is (i) an odorless yellowish wastewater with a 99.99% reduced content in polyphenols and 98% reduced COD, (ii) an extract rich in polyphenols and lactones with high antioxidant activity and high added value, (iii) an extract containing the coloring substances of the olive fruit, and (iv) pure hydroxytyrosol. PMID- 17348674 TI - Polymethoxylated flavones and other phenolic derivates from citrus in their inhibitory effects on P-glycoprotein-mediated transport of talinolol in Caco-2 cells. AB - Many studies investigating drug interactions with citrus compounds focus on the major grapefruit furanocoumarins bergamottin, dihydroxybergamottin, and the flavonoid naringenin. This study evaluated the influence of polymethoxylated flavones (PMFs), tangeretin, nobiletin, 3,5,6,7,8,3,4'-heptamethoxyflavone, and sinensetin, as well as other minor occurring citrus phenols, hesperetin, limettin, 7-OH-coumarin, 7-geranyloxycoumarin, and eriodictyol, on P-glycoprotein mediated transport of the beta-blocker talinolol using the Caco-2 cell monolayer model and was used to determine the structure-function aspects of the interaction. The transport of talinolol across Caco-2 cells monolayers was determined in the absence and presence of distinct concentrations of the calcium channel blocker verapamil (a known inhibitor of P-glycoprotein) and citrus compounds. A sigmoid dose-response model was used to fit the data and to estimate the IC50 values of the potential inhibitors. Results from this study show that PMFs significantly decreased talinolol transport from the basolateral to apical side, where tangeretin had the lowest IC50 of 3.2 micromol/L, followed by nobiletin, heptamethoxyflavone, and sinensetin with IC50 values of 3.5, 3.8, and 3.9 micromol/L, respectively. However, the efficacy of the compounds did not appear to be dependent on the number of methoxy groups. Other citrus compounds did not have any significant effect on the transport of talinolol. This study suggests that PMFs have a high potential in the interaction with P-gp-mediated talinolol transport in Caco-2 cells. Based on their relatively low concentrations (< or =3 microg/mL) in citrus, the clinical relevance of these interactions needs to be further elucidated in in vivo studies. PMID- 17348675 TI - Distribution of total aflatoxins in milled fractions of hulled rice. AB - Two varieties of hulled rice artificially contaminated with aflatoxins at five different levels were processed by dehulling and polishing methods. Contamination levels ranged from 356 to 818 microg/kg and from 244 to 645 microg/kg in medium and long grain rice, respectively. After physical processing, four different milled fractions were obtained (hull, bran, polished broken grains, and polished whole kernels). The fractions were analyzed for total aflatoxins (B1, B2, G1, and G2) by enzyme-linked immunosorbent assay (ELISA). Aflatoxins were removed in fractions intended for human consumption (polished broken grains and polished whole kernels) at rates up to 97%. They were found throughout all fractions, but higher contamination levels were detected in hull and bran fractions than in unprocessed kernels and polished fractions. Regardless of the rice variety, the aflatoxin distribution pattern depended on the initial contamination level and type of milled fraction but not on the duration of polishing. PMID- 17348676 TI - Effect of storage on cholesterol oxide formation and fatty acid alterations in egg powder. AB - The effect of the storage of egg powder on cholesterol oxide formation and alterations in the fatty acid composition was studied. Two commercial brands, A and B, were studied at 0 time and then monthly for up to 6 and 12 months, respectively. Five cholesterol oxides were identified and quantified (7 ketocholesterol, 7beta-hydroxycholesterol, 7alpha-hydroxycholesterol, 5,6alpha epoxycholesterol, and 5,6beta-epoxycholesterol), the amounts of which increased during storage, although the cholesterol contents remained constant. The polyunsaturated fatty acid contents reduced during storage, whereas the levels of saturated and monounsaturated fatty acids and total lipids remained constant. High cholesterol oxide and trans fatty acid contents were found, a fact of concern because these compounds are hazardous to health, and egg powder is used in various food products widely consumed by the population, principally by infants. PMID- 17348677 TI - Oscillatory water sorption test for determining water uptake behavior in bread crust. AB - In this work, water sorption kinetics of bread crust are described using an oscillatory sorption test in combination with a Langmuir type equation. Both kinetic and thermodynamic information could be obtained at the same time. An advantage of applying a Langmuir type equation for a quantitative description of the water uptake kinetics is that no prior knowledge is necessary with respect to shape and surface area of the sample. It was shown that adsorption and desorption of water to the bread crust particle surface is much faster than the experimental time used (15 min at minimum). From this, we may conclude that diffusion of water into the solid matrix is the rate-limiting step in the water sorption process. The method also allows one to calculate a Gibbs free energy. The method is suitable for use up to relative humidities of 60%. PMID- 17348678 TI - Statistical correlations between the in-mouth textural characteristics and the chemical composition of Shiraz wines. AB - The relationships between the levels of polyphenols, acidity, and red pigments in Shiraz wines and their perceived textural profiles as quantified by a trained sensory descriptive analysis panel were explored. A "chamois-like" feeling when the wine was held in the mouth appeared to be related to an absence of polyphenols. The in-mouth "chalk-like" texture was strongly associated with anthocyanin concentration and was negatively associated with alcohol level and acidity. The astringent subqualities of "velvet-like" and "emery-like" roughing were mostly related to polyphenol levels, but these attributes could not be adequately differentiated by the compositional variables under study. Wines that elicited a "puckery" sensation were characterized by relatively low anthocyanin levels, high acidity, and high pigmented polymer and tannin concentrations. The results of the study suggest that the in-mouth textural properties of Shiraz red wine are associated not only with their tannin composition and concentration but also with their acidity and anthocyanin and alcohol concentrations. PMID- 17348679 TI - Insecticidal benzoylphenylurea-S-carbamate: a new propesticide with two effects of both benzoylphenylureas and carbamates. AB - New propesticides with two effects of both benzoylphenylureas and carbamates were designed and synthesized by the key intermediate N-chlorosulfenyl-N methylcarbamate, which was prepared for the first time. These benzoylphenylurea-S carbamates were identified by 1H NMR spectroscopy and elemental analyses. The bioactivities of the new compounds were evaluated. These benzoylphenylurea-S carbamates exhibited excellent larvicidal activities against Oriental armyworm, some of which were good as compared to the parent benzoylphenylureas. Toxicity assays indicated that these benzoylphenylurea-S-carbamates had knockdown activities of carbamates at higher concentrations and insect growth regulator activities of benzoylphenylureas at lower concentrations. We found that the title compounds exhibited good systemic larvicidal activities against Oriental armyworm, which were especially advantageous when combating sucking pests. Some of these title compounds can kill aphids and mosquitoes as well. PMID- 17348680 TI - Insecticidal and antifungal activity of a protein from Pouteria torta seeds with lectin-like properties. AB - This paper describes the purification and characterization of a novel protein from the seeds of Pouteria torta (family Sapotaceae). The protein was purified by a combination of gel filtration, ion-exchange, and reverse phase chromatographies. SDS-PAGE of the purified protein resulted in a single protein band of 14 kDa in the presence and absence of DTT. The lectin-like activity of pouterin was best inhibited by glycoproteins such as fetuin, asialofetuin, heparin, orosomucoid, and ovoalbumin. Pouterin inhibited the growth of the fungi Fusarium oxysporum and Colletotrichum musae and of the yeast Saccharomyces cerevisiae. The incorporation of pouterin into an artificial diet (final concentration = 0.12%, w/w) caused 50% mortality in larvae of the insect Callosobruchus maculatus, whereas 0.08% pouterin produced an ED50. PMID- 17348681 TI - Flavonoids from barrel medic (Medicago truncatula) aerial parts. AB - Twenty-three flavonoids have been identified in the aerial parts of barrel medic, and their structures were established by spectrometric and spectroscopic (ESI MS/MS and NMR) techniques. Eight of the identified compounds, including apigenin 7-O-beta-D-glucuronopyranosyl-(1-->3)-O-beta-D-glucuronopyranosyl-(1-->2)-O-beta D-glucuronopyranoside, apigenin 7-O-[2'-O-sinapoyl-beta-D-glucuronopyranosyl-(1- >2)-O-beta-D-glucuronopyranoside], apigenin 7-O-{2-O-feruloyl-[beta-D glucuronopyranosyl-(1-->3)]-O-beta-D-glucuronopyranosyl-(1-->2)-O-beta-D glucopyranoside}, chrysoeriol 7-O-[beta-D-glucuronopyranosyl-(1-->2)-O-beta-D glucuronopyranoside, chrysoeriol 7-O-{2'-O-p-coumaroyl-[beta-D-glucuronopyranosyl (1-->3)]-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside}, tricin 7-O-beta-D-glucuronopyranosyl-4'-O-glucopyranoside, tricin 7-O-[2'-O-feruloyl beta-D-glucuronopyranosyl-(1-->2)-O-beta-D-glucopyranoside], and tricin 7-O-{2'-O p-coumaroyl-[beta-D-glucuronopyranosyl-(1-->3)]-O-beta-D-glucuronopyranosyl(1- >2)-O-beta-D-glucuronopyranoside}, have not been reported before in the plant kingdom. Additionally, the presence of two luteolin, three apigenin, one chrysoeriol, and six tricin glycosides, previously identified in alfalfa (Medicago sativa), was confirmed in M. truncatula. Moreover, besides the above flavones, the aerial parts of this species contained three flavonols including rutin, laricitrin 3,7,5'-triglucoside, and laricitrin 3,5'-diglucoside. PMID- 17348682 TI - Environmental fate of two sulfonamide antimicrobial agents in soil. AB - Veterinary antimicrobial agents have been detected in a number of environmental samples, including agricultural soils. In this study, we investigated the persistence and sorption of the sulfonamides sulfamethazine (SMZ) and sulfachloropyridine (SCP) in soil and their potential effects on soil microorganisms. The sulfonamides dissipated more rapidly from the silt loam soil as compared to the sandy soil. Average half-lives of SMZ and SPC among the two soils were 18.6 and 21.3 days, respectively. The presence of liquid swine slurry (5% v/w) decreased sulfonamide persistence in the silt loam soil. The lower persistence of the antimicrobials in liquid swine slurry-amended soil was likely due to higher microbial activity, as compared to unamended soil, and/or to the greater bioavailability of the sulfonamides to degrading microorganisms, as estimated by sorption isotherms. Concentrations of SMZ and SPC up to 100 microg g 1 had no effect on antimicrobial degradation rates and soil microorganisms. These studies suggest that higher sulfonamide concentrations would be necessary to affect the main processes controlling their environmental fates in soil, but at the concentrations normally found in the environment, there would be little or no effects. PMID- 17348683 TI - Proteome changes in leaves from grapevine (Vitis vinifera L.) transformed for alcohol dehydrogenase activity. AB - A proteomic approach has been used to study changes in leaf protein content from plants transformed for alcohol dehydrogenase (ADH) activity. Individual quantitative analysis of 190-436 spots separated by two-dimensional electrophoresis was performed, and spots displaying significant quantitative changes between control (C), sense (S), and antisense (R) transformants were selected using Student's t test. Of the 14 spots selected and further analyzed after trypsic digestion, 9 could be identified by MS analysis and 5 by LC-MS/MS. Identified proteins had mainly a chloroplastic origin: four rubisco large subunits, one rubisco binding protein, two glutamine synthetases, one elongation factor Tu, one ATP synthase beta subunit, and one plastidic aldolase. Proteins with other localization were also identified, such as a UDP-glucose pyrophosphorylase, a mitochondrial aminomethyltransferase, a linalool synthase, which comigrated with the protein identified as elongation factor Tu, an enolase comigrating with a glyceraldehyde 3-phosphate dehydrogenase, and a mixture of eight proteins among which were a dehydroascorbate reductase, a chalcone isomerase, and a rubisco activase. The results emphasize the changes in carbon metabolism-associated proteins linked to the alteration in ADH activity of grapevine transformant leaves. PMID- 17348684 TI - Production of hepatitis B surface antigen in recombinant plant systems: an update. AB - There is a growing interest to develop oral vaccines for infectious diseases, as it is the most convenient and effective way to attain mucosal immunity. Hepatitis B continues to be a major infectious disease in many developing countries despite the availability of recombinant vaccine. On a global scenario, Hepatitis B Virus infection is probably the single most prevalent cause of persistent viraemia in humans. There are about 350 million chronic carriers of HBV, which is about 5% of the total world population. It is estimated that 75-100 million of them will die of liver cirrhosis and/or hepatocellular carcinoma. Progress in plant genetic engineering has enabled the transfer of useful genes for desirable traits. The recent trend is to use this technique to exploit plants as biofactories for the production of therapeutic proteins including vaccines. Rapid progress has been made in this area to develop plant-based vaccines for hepatitis B. This review describes the expression, characterization, and immunogenicity studies of hepatitis B vaccines produced in recombinant plant systems and their implications for developing a plant-based vaccine. PMID- 17348685 TI - Vascular endothelial growth factor receptor-3 activity is modulated by its association with caveolin-1 on endothelial membrane. AB - Vascular endothelial growth factor receptor-3 (VEGFR-3) is constitutively expressed in lymphatic vessels and transiently in endothelial cells of blood vessels during angiogenesis. Here we report that VEGFR-3 localizes in the caveolae membrane of endothelial cells and co-immunoprecipitates with caveolin-1. Caveolin-1 silencing or its depletion from the cell membrane by cholesterol increases VEGFR-3 autophosphorylation, suggesting that caveolin acts as a negative regulator of VEGFR-3 activity. Receptor activation induces caveolin-1 phosphorylation on tyrosine residues including tyrosine 14. Cell treatment with Src or Abl inhibitors PP2 or STI571, prior to receptor stimulation, affects caveolin-1 phosphorylation without affecting receptor autophosphorylation, suggesting that both Src and Abl are involved in VEGFR-3-dependent caveolin-1 phosphorylation. Caveolin-1 phosphorylation in Src/Fyn/Yes knockout cells demonstrated that Abl phosphorylates caveolin-1 independently from Src family members. These results suggest a functional interaction between VEGFR-3 and caveolin-1 to modulate endothelial cell activation during angiogenesis. PMID- 17348686 TI - Crosstalk between PSD-95 and JIP1-mediated signaling modules: the mechanism of MLK3 activation in cerebral ischemia. AB - Our previous study indicates that global ischemia facilitates the assembly of the GluR6.PSD-95.MLK3 signaling module, which in turn activated MLK3, leading to exacerbated ischemic neuron death. In addition, JIP1, functioning as a scaffold protein, could couple MLK3-MKK7-JNK to form a specific signaling module and facilitate the activation of the JNK signal pathway. However, the organization, regulation, and function between the two signaling modules and the effects they have on MLK3 activation remain incompletely understood. Here, we show that JIP1 maintains MLK3 in an inactive and monomeric state; once activated, MLK3 binds to PSD-95 and then dimerizes and autophosphorylates. In addition, a GluR6 C-terminus containing peptide (Tat-GluR6-9c) and antisense oligonucleotides (AS-ODNs) against PSD-95 inhibit the integration of PSD-95 and MLK3 and the dimerization of MLK3, facilitate the interaction of JIP1 and MLK3, and, consequently, perform neuroprotection on neuron death. However, AS-ODNs against JIP1 play a negative role compared to that mentioned above. The findings show that the crosstalk occurs between PSD-95 and the JIP1-mediated signaling module, which may be involved in brain ischemic injury and contribute to the regulation of MLK3 activation. Thus, specific blockade of PSD-95-MLK3 coupling may reduce the extent of ischemia-reperfusion-induced neuronal cell death. PMID- 17348687 TI - Biochemical and in vivo characterization of a small, membrane-permeant, caspase activatable far-red fluorescent peptide for imaging apoptosis. AB - Apoptosis is an important process involved in diverse developmental pathways, homeostasis, and response to therapy for a variety of diseases. Thus, noninvasive methods to study regulation and to monitor cell death in cells and whole animals are desired. To specifically detect apoptosis in vivo, a novel cell-permeable activatable caspase substrate, TcapQ647, was synthesized and Km, kcat, and Ki values were biochemically characterized. Specific cleavage of TcapQ647 by effector caspases was demonstrated using a panel of purified recombinant enzyme assays. Of note, caspase 3 was shown to cleave TcapQ647 with a kcat 7-fold greater than caspase 7 and 16-fold greater than caspase 6. No evidence of TcapQ647 cleavage by initiator caspases was observed. In KB 3-1 or Jurkat cells treated with cytotoxic agents or C6-ceramide, TcapQ647 detected apoptosis in individual- and population-based fluorescent cell assays in an effector caspase inhibitor-specific manner. Further, only background fluorescence was observed in cells incubated with dTcapQ647, a noncleavable all d-amino acid control peptide. Finally, in vivo experiments demonstrated the utility of TcapQ647 to detect parasite-induced apoptosis in human colon xenograft and liver abscess mouse models. Thus, TcapQ647 represents a sensitive, effector caspase-specific far-red "smart" probe to noninvasively monitor apoptosis in vivo. PMID- 17348688 TI - Identification of multiple amyloidogenic sequences in laminin-1. AB - Amyloid fibril formation is associated with several pathologies, including Alzheimer's disease, Parkinson's disease, type II diabetes, and prion diseases. Recently, a relationship between basement membrane components and amyloid deposits has been reported. The basement membrane protein, laminin, may be involved in amyloid-related diseases, since laminin is present in amyloid plaques in Alzheimer's disease and binds to amyloid precursor protein. Recently, we showed that peptide A208 (AASIKVAVSADR), the IKVAV-containing peptide, formed amyloid-like fibrils. We previously identified 60 cell adhesive sequences in laminin-1 using a total of 673 12-mer synthetic peptides. Here, we screened for additional amyloidogenic sequences among 60 cell adhesive peptides derived from laminin-1. We first examined amyloid-like fibril formation by the 60 active peptides with Congo red, a histological dye binding to many amyloid-like proteins. Thirteen peptides were stained with Congo red. Four of the 13 peptides promoted cell attachment and neurite outgrowth like the IKVAV-containing peptide. The four peptides also showed amyloid-like fibril formation in both X-ray diffraction and electron microscopic analyses. The amyloidogenic peptides contain consensus amino acid components, including both basic and acidic amino acids and Ser and Ile residues. These results indicate that at least five laminin-derived peptides can form amyloid-like fibrils. We conclude that the laminin-derived amyloidogenic peptides have the potential to form amyloid-like fibrils in vivo, possibly when laminin-1 is degraded. PMID- 17348689 TI - NEIL1 is the major DNA glycosylase that processes 5-hydroxyuracil in the proximity of a DNA single-strand break. AB - 5-Hydroxyuracil (5-OHU) in DNA, arising during endogenous DNA damage and caused by ionizing radiation, is removed by the base excision repair pathway. However, in addition to base lesions, ionizing radiation also generates DNA single-strand breaks (SSBs). When these DNA lesions are located in the proximity of each other, this may result in a profound effect on both repair of the damaged base and the SSB. We therefore examined the repair of DNA substrates containing 5-OHU lesions in the proximity of the 3'-end of a SSB. We found that SSB repair by DNA ligase IIIalpha and DNA polymerase beta is impaired by the presence of the nearby 5-OHU lesion, indicating the requirement for a DNA glycosylase which would be able to remove 5-OHU before SSB repair. Subsequently, we found that although both SMUG1 and NEIL1 are able to excise 5-OHU lesions located in the proximity of the 3'-end of a DNA SSB, NEIL1 is more efficient in the repair of these DNA lesions. PMID- 17348690 TI - Kinetic and structural studies on interactions between heparin or heparan sulfate and proteins of the hedgehog signaling pathway. AB - Heparan sulfate (HS) proteoglycans (PGs) interact with a number of extracellular signaling proteins, thereby playing an essential role in the regulation of many physiological processes. These interactions are important for both normal signal transduction and regulation of the tissue distribution of signaling molecules. In this study, we use surface plasmon resonance (SPR) to study interactions of HS and structurally related heparin with proteins in the Hedgehog signaling pathway. SPR analysis shows that heparin binds with different affinities to active fragments of the proteins Hedgehog (Hh), Interference Hedgehog (Ihog), Cam related/Down-regulated by Oncogenes (CDO), and Sonic Hedgehog (Shh). Solution competition studies show that the minimum size of a heparin oligosaccharide capable of interacting with Ihog is larger than a tetrasaccharide and for interacting with Shh is larger than an octasaccharide. In comparison with heparin, Ihog and Shh exhibited a lower affinity for HS than for heparin, and CDO and Hh exhibit negligible binding to HS. This study clearly demonstrates Shh and Ihog are heparin and HS binding proteins and that both molecules preferentially bind heparin or HS having a high level of sulfation. PMID- 17348693 TI - On the nature of the Bronsted acidic groups on native and functionalized mesoporous siliceous SBA-15 as studied by benzylamine adsorption from solution. AB - The concentration and Bronsted acidity of surface silanol groups on mesoporous silica (SBA-15) has been studied by following the adsorption of benzylamine, BA, from water as a function of pH. The adsorbed amount of BA from water was compared to the maximum amount of BA that could be adsorbed from cyclohexane. Furthermore, the surface concentration and acidity of carboxylic acid functions on surface functionalized SBA-15 was also studied, which allowed the relative surface concentration of remaining silanols to be obtained. Two types of silanols can be identified, where about 1/5 of the silanols have a pKa 100 degrees C). In all heterogeneous systems with solid Pd catalysts, Pd is dissolved from the solid catalyst surface under reaction conditions by a chemical reaction (complex formation and/or oxidative addition of the aryl halide), forming extremely active coordinatively unsaturated Pd species. Pd is partially or completely redeposited onto the support at the end of the reaction when the aryl halide is used up. The Pd dissolution-redeposition processes correlate with the reaction rate and are strongly influenced by the reaction conditions. Skilled preparation of the catalyst and careful adjustment of the reaction conditions allowed the development of highly active heterogeneous catalysts (Pd/C, Pd/metal oxide, and Pd/zeolite), converting aryl bromides and aryl chlorides in high yields and short reaction times. Reaction conditions have been developed allowing the conversion of bromobenzene with turnover numbers (TONs) of 10(7) and even of unreactive aryl chlorides (chlorobenzene and chlorotoluene) in high yields with simple "ligand-free" Pd catalyst systems like PdCl2 or Pd(OH)2 in the absence of any organic ligand. Simple coordinatively unsaturated anionic palladium halide (in particular, bromo) complexes [PdXn](m-) play a crucial role as precursor and active species in all ligand-free and heterogeneous catalyst systems and possibly in Heck reactions at all. PMID- 17348719 TI - Palladium nanoparticles as efficient green homogeneous and heterogeneous carbon carbon coupling precatalysts: a unifying view. AB - Pd catalysis of C-C bond formations is briefly reviewed from the angle of nanoparticles (NPs) whether they are homogeneous or heterogeneous precatalysts and whether they are intentionally preformed or generated from a Pd derivative such as Pd(OAc)2. The most studied reaction is the Heck coupling of halogenoarenes with olefins that usually proceeds at high temperature (120-160 degrees C). Under such conditions, the PdII precursor is reduced to Pd0, forming PdNPs from which Pd atom leaching, subsequent to oxidative addition of the aryl halide onto the PdNP surface, is the source of very active molecular catalysts. Other C-C coupling reactions (Suzuki, Sonogashira, Stille, Negishi, Hiyama, Corriu-Kumada, Ullmann, and Tsuji-Trost) can also be catalyzed by species produced from preformed PdNPs. For catalysis of these reactions, leaching of active Pd atoms from the PdNPs may also provide a viable molecular mechanistic scheme. Thus, the term "PdNP catalysis of C-C coupling" used in this review refers to this function of PdNPs as precursors of catalytically active Pd species (i.e., the PdNPs are precatalysts of C-C coupling reactions). PMID- 17348720 TI - Homogeneous nanosize palladium catalysts. AB - Expanding the catalytic environment to a nanosize must be one of the most promising ways to improve the performance of homogeneous catalysts. In this Forum Article, recent developments in homogeneous nanosize palladium catalysts are reviewed. It contains solubilized palladium nanoparticles, metalated dendrimers, and complexes with well-defined nanosized ligands. These systems realize efficient catalyst recycling, unique selectivity, suppression of metal aggregation, and remarkable enhancement of the catalytic activity. PMID- 17348721 TI - Recent progress in Wacker oxidations: moving toward molecular oxygen as the sole oxidant. AB - Wacker oxidations, the conversion of terminal olefins to methyl ketones with Pd(II) catalysts, have seen widespread use in synthetic applications. Standard synthetic Wacker conditions use catalytic PdCl2 with stoichiometric CuCl under an aerobic atmosphere in a mixed-solvent system of N,N-dimethylformamide and H2O. Though much attention has been directed toward elucidating the rate-determining step and the mechanism of nucleopalladation, the assumption that Cu does not participate in this portion of the catalytic cycle has recently been called into question based on an isolated Pd/Cu bimetallic species and the influence of Cu on product selectivity. Fortunately, recent advancements have been made toward the elimination of Cu additives, thereby alleviating these issues. Success in this area has come from the application of information gained in studying other direct O2-coupled Pd(II) oxidation systems, including ligand modulation, something which could not be achieved in the presence of Cu. The developments in peroxide mediated and direct-O2-coupled Wacker oxidations are highlighted herein. PMID- 17348722 TI - Palladium-catalyzed aerobic oxidative amination of alkenes: development of intra- and intermolecular aza-Wacker reactions. AB - Palladium-catalyzed methods for the aerobic oxidative coupling of alkenes and oxygen nucleophiles (e.g., water and carboxylic acids) have been known for nearly 50 years. The present account summarizes our development of analogous aerobic oxidative amination reactions, including the first intermolecular aza-Wacker reactions compatible with the use of unactivated alkenes. The reactions are initiated by intra- or intermolecular aminopalladation of the alkene. The resulting alkylpalladium(II) intermediate generally undergoes beta-hydride elimination to produce enamides or allylic amide products, but in certain cases, the Pd-C bond can be trapped to achieve 1,2-difunctionalization of the alkene, including carboamination and aminoacetoxylation. Mechanistic studies have provided a variety of fundamental insights into the reactions, including the effect of ancillary ligands on palladium catalysts, the origin of the Bronsted base-induced switch in regioselectivity in the oxidative amination of styrene, and evidence that both cis- and trans-aminopalladations of alkenes are possible. Overall, these reactions highlight the potential utility of an "organometallic oxidase" strategy for the selective aerobic oxidation of organic molecules. PMID- 17348723 TI - Reactions of hypervalent iodine reagents with palladium: mechanisms and applications in organic synthesis. AB - The unique reactivity of hypervalent iodine reagents with Pd0 and PdII complexes has been exploited for a variety of synthetically useful organic transformations. For example, IIII reagents have been used in place of aryl halides for diverse Pd catalyzed C-C and C-heteroatom bond-forming cross-coupling reactions. In addition, these reagents have found application in Pd-catalyzed oxidation reactions, including the oxidative functionalization of C-H bonds and the 1,2 aminooxygenation of olefinic substrates. This review discusses both the synthetic utility and the interesting mechanistic features of these transformations. PMID- 17348724 TI - Electronic effects on reductive elimination to form carbon-carbon and carbon heteroatom bonds from palladium(II) complexes. AB - The electronic properties of reactive and ancillary ligands have a large impact on the rate and scope of reductive elimination reactions. The purpose of this review is to compare and discuss published data on the effect of ligand electronic properties on the rates and scope of reductive eliminations from palladium(II). An understanding of these effects is important because reductive elimination from palladium(II) is the product-forming step of a variety of catalytic processes. The scope of this review will encompass the effect of the electron-donating abilities of alkyl, aryl, amido, alkoxo, thiolato, and phosphido groups on the rate of reductive elimination, the relative importance of inductive and resonance effects on the rate of reductive elimination, the relative sensitivity of the different classes of reductive eliminations to electronic perturbations, and the effect of the differences in electronic properties between the two aryl groups of biaryl complexes undergoing reductive elimination. In addition, this review will include the effects of electronic properties of the ancillary ligands on the rate of reductive eliminations from palladium(II). The effect of the overall electron-donating ability of ancillary ligands and the effect of the relative orientation of ancillary ligands to the two reactive ligands on the rate of reductive elimination will be discussed. Where appropriate, electronic effects on reductive elimination from complexes of other metals are described. PMID- 17348725 TI - Phase-switch synthesis with boronic acids as productive tags. PMID- 17348726 TI - Chemoselective reduction of nitroarenes in the presence of acid-sensitive functional groups: solid-phase syntheses of amino aryl azides and benzotriazoles. PMID- 17348727 TI - Traceless solid-phase synthesis and biological evaluation of purine analogs as inhibitors of multidrug resistance protein 4. AB - The traceless solid-phase syntheses of 6-oxopurines and pyrazolo[3,4 d]pyrimidines are presented. The effects of these compounds on multidrug resistance protein 4 (MRP4/ABCC4) facilitated efflux was examined. Four of the compounds, 7b, 7c, 15a, and 17e, were active in inhibiting MRP4-mediated efflux of the bimane-glutathione conjugate. In addition, all four compounds were also able to reverse MRP4-mediated resistance to the anticancer drug 6-thioguanine. In the presence of 25 microM 15a or 17e, there was complete reversal. The reversal of resistance was achieved without any effects on the uptake and metabolism of 6 thioguanine. PMID- 17348728 TI - Combinatorial solution-phase synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2 carboxamides. AB - Solution-phase combinatorial synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2 carboxamides was studied. First, di-tert-butyl (2S,4S)-4-amino-5-oxopyrrolidine 1,2-dicarboxylate hydrochloride was prepared as the key intermediate in five steps from (S)-pyroglutamic acid. Acylation of the amino group followed by acidolytic deprotection gave (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxylic acids, which were then coupled with amines to furnish a library of (2S,4S)-4 acylamino-5-oxopyrrolidine-2-carboxamides. Four coupling reagents, BPC, EEDQ, TBTU, and PFTU, were tested for the amidation reactions in the final step. Amidations with EEDQ and TBTU led to the desired carboxamides. On the other hand, BPC and PFTU were not suited, since diketopiperazines were sometimes obtained instead of the desired carboxamides. PMID- 17348729 TI - Combinatorial synthesis and hydrogenation of Mg/Al libraries prepared by electron beam physical vapor deposition. AB - We have grown thin film libraries of the Mg-Al system using a high-throughput synthesis methodology that combines the sequential deposition of pure elements (Mg and Al) by an electron-beam (e-beam) evaporation technique and the use of a special set of moving shadow masks. This novel mask has been designed to simultaneously prepare four identical arrays of different compositions that will permit the characterization of the same library after several treatments. Wavelength dispersive spectroscopy (WDS) and micro-X-ray diffraction have been used as high-throughput screening techniques for the determination of the composition and structure of every member of the library in the as-deposited state and after hydrogenation at 1 atm of H2 during 24 h at three different temperatures: 60, 80, and 110 degrees C. We have analyzed the influence of the Mg Al ratio on the hydrogenation of magnesium, as well as on the appearance of complex hydride phases. We have also found that aluminum can act as a catalyzer for the hydrogenation reaction of magnesium. PMID- 17348730 TI - Ring-opening and ring-closing reactions of a shikimic acid-derived substrate leading to diverse small molecules. AB - An epoxide derived from (-)-shikimic acid was attached to a solid support and used to synthesize over 5000 diverse small molecules. Key transformations include a Lewis acid-catalyzed epoxide opening with amines and an intramolecular Heck reaction with aryl iodides. Compounds derived from this pathway were printed onto small-molecule microarrays and screened for binding to proteins. Compounds that bound to Aurora A kinase were characterized using surface plasmon resonance. PMID- 17348731 TI - On-line synthesis of pseudopeptide library incorporating a benzodiazepinone turn mimic: biological evaluation on MC1 receptors. AB - Alpha melanocyte stimulating hormone (alpha-MSH) is a widely distributed hormone. This tridecapeptide exhibits various biological activities mediated through different receptors. alpha-MSH binds to the melanocortin-1 receptor (MC1-R), mainly expressed in keratinocytes and melanocytes, inducing melanogenesis and anti-inflammatory processes. The central His-Phe-Arg-Trp tetrapeptide sequence of alpha-MSH is known to form a turn in the bioactive conformation. To find new potent analogs of alpha-MSH, we decided to introduce non-peptide building blocks in the alpha-MSH sequence. Molecular modeling studies showed that two amino acids of the central core sequence could be replaced by the benzodiazepinone building block without loosing the beta-turn conformation. Benzodiazepines are well-known pharmacophores exhibiting a wide scope of biological activities and are described as constrained dipeptide mimics templates. Although numerous synthetic pathways leading to benzodiazepinones have been described in literature, no methodology has 1,4-benzodiazepine-2,5-diones building blocks bearing a free carboxylic acid function and a protected amino function suitable for incorporation into peptide sequences. In this study, we report the synthesis of peptides with a benzodiazepinone moiety obtained directly during the course of solid-phase peptide synthesis (SPPS). This "on-line" strategy leads to the generation of a 54 member pseudo-peptide library of alpha-MSH analogs. After LC/MS purification, binding assays were performed on the MC1 receptor leading to the discovery of several micromolar ligands. PMID- 17348732 TI - Stereoselective aza Diels-Alder reaction on solid phase: a facile synthesis of hexahydrocinnoline derivatives. AB - As part of our continuing studies of polymer-supported pericyclic reactions for preparing biologically interesting heterocyclic compounds, we have introduced a traceless solid-phase synthesis of hexahydrocinnolines. We developed a method in which mild reaction conditions can be used for the hetero-Diels-Alder reactions on a polymeric support. The dienoic 3-vinyl-2-cyclohexenol attached to a Wang resin through an ether linkage undergoes [4 + 2] cycloaddition reaction with several azadienophiles. The highly stereoselective Diels-Alder reaction showed preferential formation of a single cycloadduct resulting from an anti attack of the dienophile on the polymer-bound diene. Trifluoroacetic acid-mediated cleavage of the polymer-bound cycloadducts yields fused nonaromatic hexahydrocinnolines in moderate yields in three steps. PMID- 17348733 TI - Microwave-assisted solution- and solid-phase synthesis of 2-amino-4 arylpyrimidine derivatives. AB - An efficient and rapid microwave-assisted solution-phase method for the synthesis of 2-amino-4-arylpyrimidine-5-carboxylic acid derivatives has been developed. The five-step linear protocol involves an initial Biginelli multicomponent reaction leading to dihydropyrimidine-2-thiones which are subsequently S-alkylated with methyl iodide. The resulting 2-methylthiodihydropyrimidines are sequentially oxidized first with manganese dioxide and then with Oxone to provide 2 methylsulfonyl-pyrimidines which serve as excellent precursors for the generation of a variety of 2-substituted pyrimidines via displacement of the reactive sulfonyl group with nitrogen, oxygen, sulfur, and carbon nucleophiles. A modified protocol using a solid-phase method has also been developed. PMID- 17348734 TI - High-throughput microwave-assisted organic synthesis: moving from automated sequential to parallel library-generation formats in silicon carbide microtiter plates. AB - A 48 deep-well microtiter plate system for sealed vessel parallel microwave synthesis is described. The plate consists of a standard 6 x 8 matrix of 48 wells with a maximum working volume of 300 microL and is made out of strongly microwave absorbing sintered silicon carbide. In combination with an alumina sealing plate equipped with adequate conical bore holes for sample withdrawal, the setup can be used for microwave processing at temperatures up to approximately 200 degrees C and 20 bar of pressure. The microtiter plate setup displays excellent temperature and reaction homogeneity and was used for the generation of a 30-member library of 2-aminopyrimidines. PMID- 17348735 TI - Nanoporous magnesium aluminometasilicate tablets for precise, controlled, and continuous dosing of chemical reagents and catalysts: applications in parallel solution-phase synthesis. AB - Mechanically robust tablets of nanoporous magnesium aluminometasilicate with high surface area and porosity can be loaded with a variety of organic and inorganic reagents and catalysts. The scope of this novel dosing methodology is demonstrated through the evaluation of 14 diverse organic reactions, including Mitsunobu, Suzuki, and bromination reactions. PMID- 17348736 TI - Accessibility and affordability of malaria intervention, treatment and prevention in Africa. PMID- 17348737 TI - The changing conceptions and focus of health research in East Africa. AB - Perceptions in health research are a product of the circumstances within the society, where the research activities are situated. In East Africa there has been a change in conceptualization over a period of time from an elitist de linked status to the present, which has evolved to embrace the local community. Here we trace the changes and highlight some occurrences that exerted the greatest influence in shaping the notions that currently dominate in research. We conclude that the paradigm shift is a positive development and that the present conception is suitable for heath research at this point in time. PMID- 17348738 TI - Situational analysis of leishmaniases research in Kenya. AB - Leishmania spp are protozoan parasites of the Trypanosomatidae family that cause disease in humans and animals. In general, infections with these parasites can be divided into three main forms namely, cutaneous, mucocutaneous, and visceral leishmaniases. The disease is prevalent in many tropical and subtropical regions of the world, where it is transmitted via the bite of an infected sand fly. Leishmaniasis has been known to be endemic in parts of Kenya from as far back as early in the 20th century. These endemic areas include Turkana, Baringo, Kitui, Machakos, Meru, West Pokot and Elgeyo Marakwet districts which have been reported to be endemic for kala-azar. Recent outbreaks of VL have been reported in the previously non-endemic districts of Wajir and Mandera in North Eastern Kenya between May 2000 and August 2001. The vector for VL in Kenya is Phlebotomus martini though other vectors including P. orientalis have been reported. Baringo district is the only foci reported where both VL and CL are known to occur in Kenya. The aetiological agents for CL which include L. major which has been reported in Baringo; L. tropica in Laikipia, Samburu, Isiolo, Nakuru and Nyandarua districts while L. aethiopica has been reported in the Mt Elgon area. In Kenya, P. duboscqi, P. guggisbergi have been shown to be the vectors of L. major and L. tropica, respectively, while P. pediffer, P. longipes and P. elgonensis have been implicated as vectors of L. aethiopica. Since 1980, the Kenya Medical Research Institute (KEMRI) has spearheaded research on leishmaniases research in Kenya focusing on various aspects including characterization of Leishmania species, biology, and ecology of sand fly vectors, development of biological strategies for sand fly control, identification of animal reservoirs, diagnosis, new treatment strategies, new chemotherapeutic agents, and vaccine-related studies. KEMRI, a founding partner of the Drugs for Neglected Disease Initiative (DNDi), whose overall aim is to address lack of new or improved drugs for neglected diseases (which include leishmaniases, malaria, trypanosomiasis and Chagas disease) has made major contributions in leishmaniases research and control in Kenya and the eastern Africa region. PMID- 17348739 TI - Roll Back Malaria and the new partnership for Africa's development: is there potential for synergistic collaboration in partnerships? AB - This synopsis seeks to highlight and promote the enormous potential that exists between these two initiatives that seek to address closely related issues and targeting the same populations at risk within a fairly well defined geographical setting. It also attempts to argue that malaria control, just like HIV-AIDS control, be given high priority in the New Partnership for Africa's Development (NEPAD) health agenda, as current statistics indicate that malaria is again on the rise. While much attention and billions of dollars have rightly been given to HIV-AIDS research, treatment and prevention, malaria, and not AIDS, is the region's leading cause of morbidity and mortality for children under the age of five years. This is the bad news. The good news is that unlike AIDS, malaria treatment and prevention are relatively cheap. In addition, there is a payback to fighting malaria; support aimed directly at improving health, rather than poverty reduction, may be a more effective way of helping Africa to thrive. Robust and sustained growth may come to Africa through a mosquito net, Artemisinin-based Combination Therapies (ACTs) or a malaria vaccine, rather that a donor's cheque for economic development initiatives. PMID- 17348740 TI - Acute flaccid paralysis: a five-year review of cases managed by physiotherapy at the University College Hospital, Ibadan. AB - A 5-year (1999-2004) review of acute flaccid paralysis (AFP) cases managed at the physiotherapy clinic of the University College Hospital, Ibadan Nigeria was carried out. Collection of data involved retrieving the records of all patients seen at the physiotherapy clinic during the study period, from which the paediatric cases were sorted out. The treatment records cards of patients with acute flaccid paralysis were identified and reviewed. Information on age, gender, immunization history, and specific physician diagnosis and discharge practice were collated. A total of 757 paediatric cases reviewed out of which 132 (17.4 %) were AFP case, with mean age of 44.31+ 33.03 months and a 1.2:1.0 male: female ratio. Sciatic nerve palsy accounted for majority (72.0 %) of the AFP; only 43.2 % of the patients had completed immunization before the onset; majority of the cases (78.8 %) were referred to physiotherapy within 6 months of onset and the discharge pattern revealed that only 9.8 % of the patients were formally discharged. With injection palsy accounting for majority of the AFP cases, the need for caution in administration of intramuscular injections at the buttocks of children with febrile illnesses is suggested. Importance of adequate documentation of clinical information by clinicians is also emphasised. PMID- 17348741 TI - Antiplasmodial activities of some products from Turreanthus africanus (Meliaceae). AB - We investigated the antiplasmodial activity of some pure compounds of Turreanthus africanus (Meliaceae), a plant that is used in traditional medicine to treat malaria in Southwest Cameroon. A phytochemical analysis of the methylene chloride: methanol (1:1) extract of the seeds of the plant yielded seven compounds. Four of them, which were oils, were subjected to in vitro bioassays on Plasmodium falciparum F 32, chloroquine sensitive strain. Compound 1 (16-oxolabda 8 (17), 12(E)-dien-15-oic acid), showed the highest antiplasmodial activity, two others (methyl-14,15-epoxylabda-8 (17), 12(E)-diene-16-oate, and turreanin A), had moderate activity and one was inactive. These findings are consistent with the use of T. africanus in the traditional treatment of P. falciparum malaria. PMID- 17348742 TI - Environmental factors affecting malaria parasite prevalence in rural Bolifamba, South West Cameroon. AB - The impact of some environmental factors on malaria parasite prevalence was investigated in rural Bolifamba, Cameroon. The study population comprised 1454 subjects aged 0 - 65 years. Malaria parasite prevalence was higher in the rainy (50.1 %) than in the dry season (44.2 %) with a significant difference (P = 0.001) in mean parasite density between seasons. Individuals < 15 years old had significantly higher malaria parasite prevalence (55.5 %) than those > 15 years (37.4 %). Malaria parasite prevalence (P = 0.001) and parasite density (P = 0.03) were higher in the individuals of wooden plank houses than those of cement brick houses. Inhabitants of houses surrounded by bushes or garbage heaps and swamps or stagnant water showed higher malaria parasite prevalence and densities compared with those from cleaner surroundings. Anopheles gambiae (63.8 %) and A. funestus (32.8 %) were associated with perennial transmission of malaria. Our data indicates that poor environmental sanitation and housing conditions may be significant risk factors for malaria parasite burden in Bolifamba. PMID- 17348743 TI - Influence of age of mice on the susceptibility to murine schistosomiasis infection. AB - Intensity of human schistosomiasis infection increases with age, a peak being attained at early puberty. Hormones could be involved in the age-related changes in susceptibility to schistosomiasis. Male BALB / c mice were infected with Schistosoma mansoni either before or after puberty and worm numbers, cellular immune responses, hormonal levels and pathology analysed. Pre-puberty infected mice had a significantly higher number of adult worms (p < 0.05), more severe granulomas, higher mortality rate and higher proliferative responses as compared to post-puberty infected mice. Levels of the hormones were lower in the pre puberty infected mice as compared to the post-puberty group early in the infection. Plasma levels of testosterone and luteinizing hormones decreased significantly (p < 0.05) in infected mice when compared to controls. Susceptibility to S. mansoni in male BALB / c mice seems to be influenced by levels of testosterone and luteinizing hormone at infection. Albeit, an infection with S. mansoni seems to lower the hormonal levels. PMID- 17348744 TI - The effect of vaccinating S. mansoni-infected BALB/c mice either before or after treatment. AB - In Schistosoma mansoni endemic areas, there are people with ongoing S. mansoni infection, others have been infected and treated while others have never been infected. What would happen if these different groups of people were vaccinated against S. mansoni? BALB / c mice were divided into five groups: Infected-Treated Vaccinated; Infected-Vaccinated-Treated; Vaccinated-Treated Control; Challenge Control and Untreated Challenge Control. Vaccination (500 20krad irradiated S. mansoni cercariae), Treatment (praziquantel), Infection and Challenge (150 S. mansoni cercariae) were carried out at specified times. Proliferation assay, Enzyme linked immunosorbent assay, gross pathology, histopathology and perfusion were performed. High protection levels were obtained in mice treated after vaccination: Vaccinated-Treated control, 96.5 %; Infected-Vaccinated-Treated, 68.9 %; and Infected-Treated-Vaccinated, 41 %. A good correlation was obtained between proliferative responses and protective levels, implying cellular involvement in protection. Although all protected animals had high IgG levels, there was no strong correlation between the two. Specificity rather than amounts of IgG, seem more important in protection. Praziquantel seemed to boost protective immunity when administered after vaccination. Granuloma development and modulation in the two test groups was similar. It seems better to vaccinate infected patients before treatment, the ideal situation being vaccinating people who have not encountered S. mansoni. PMID- 17348745 TI - Community-directed treatment of lymphatic filariasis in Kenya and its role in the national programmes for elimination of lymphatic filariasis. AB - We conducted a prospective, cross-sectional study to examine and compare treatment coverage of lymphatic filariasis by the health system (HST) and a health system implemented, community-directed treatment for the control of lymphatic filariasis (ComDT / HS) in 44 randomly selected villages in coastal Kenya. Demographic information on the villages and peripheral health facilities to guide design and implementation was obtained from a situation analysis phase of this study. A series of interactive training sessions on basic biology of lymphatic filariasis, concept and philosophy of ComDT / HS were given to members of the District Health Management Team (DHMT), peripheral health staff, community leaders and community drug distributors (CDDs) prior to ivermectin distribution. An intensive sensitization process of the community by the trained peripheral health staff and community leaders followed before selection of the CDDs. Quantitative and qualitative data for evaluation of the study were collected by coverage surveys of randomly selected households, focus group discussions and interviews, immediately after the drug distribution. Treatment coverage of all eligible persons was 46.5 and 88 % in HST and ComDT/HS villages, respectively, P < 0.001. In comparing treatment coverage by the two study arms in relationship to the distance from a health facility, coverage among HST and not ComDT / HS villages was influenced by distance. In Kenya, ComDT / HS can effectively be implemented by the regular health system and can attain coverage levels compatible with the global filariasis elimination goal. PMID- 17348746 TI - Trend of HIV-seropositivity among children in a tertiary health institution in the Niger Delta Region of Nigeria. AB - The objective of the study was to investigate the recent trends and magnitude of pediatric HIV-infection in the Niger Delta of Nigeria. It is a descriptive study of 1,559 consecutively recruited children (0-16 years), in whom laboratory requests for HIV screening were made, and seen in the Pediatrics Department of the University of Port Harcourt Teaching Hospital between January 1999 to December 2004 were evaluated for HIV-infection. The overall prevalence obtained was 25.8 %. HIV-1 constituted the predominant viral serotype (97.6 %) compared to HIV-2 (2.4 %). The peak HIV seropositivity occurred in pediatrics 6-8 years. There was no statistically significant difference in prevalence rate based on gender (OR = 1, p = 0.98). Children with clinical diagnosis of bronchopneumonia, neonatal sepsis, septicemia and pulmonary tuberculosis had higher prevalence of HIV seropositivity. There is a trend of increasing HIV prevalence from 1999 to 2004 (chi 2 for trend= 6.23, p = 0.39). History of previous blood transfusion was not significantly associated with HIV positivity (OR = 0.94, p = 0.94). This study shows that, in spite of the anti HIV campaign, there is a high prevalence of HIV among children attending tertiary health institution in the Niger Delta of Nigeria and the trend is increasing over the last 5 years. This calls for a re intensified effort on health education and risk control programme, provision of antiretroviral regimen to prevent mother-to-child transmission of HIV, provision of supportive environment for voluntary counseling and confidential testing of pregnant women coupled with the provision of pediatric antiretroviral therapy to reduce HIV-related mortality and morbidity of HIV-infected Nigerian children. PMID- 17348747 TI - Effects of maternal mortality on gross domestic product (GDP) in the WHO African region. AB - WHO African region has got the highest maternal mortality rate compared to the other five regions. Maternal mortality is hypothesized to have significantly negative effect on the gross domestic product (GDP). The objective of the current study was to estimate the loss in GDP attributable to maternal mortality in the WHO African Region. The burden of maternal mortality on GDP was estimated using a double-log econometric model. The analysis is based on cross-sectional data for 45 of the 46 Member States in the WHO African Region. Data were obtained from UNDP and the World Bank publications. All the explanatory variables included in the double-log model were found to have statistically significant effect on per capita gross domestic product (GDP) at 5 % level in a t-distribution test. The coefficients for land (D), capital (K), educational enrollment (EN) and exports (X) had a positive sign; while labor (L), imports (M) and maternal mortality rate (MMR) were found to impact negatively on GDP. Maternal mortality of a single person was found to reduce per capita GDP by US $ 0.36 per year. The study has demonstrated that maternal mortality has a statistically significant negative effect on GDP. Thus, as policy-makers strive to increase GDP through land reform programs, capital investments, export promotion and increase in educational enrollment, they should always remember that investment in maternal mortality reducing interventions promises significant economic returns. PMID- 17348748 TI - A skin colour code for the Nigerian (Negroid) population. AB - Some researchers have codified various people of different racial and pigment backgrounds into skin types. The West African native population generally falls into type VI--least likely to burn. There is a need for skin colour code in a multiethnic country like Nigeria especially for the purpose of health matters. The human eye is still the most accurate instrument for the measurement of colour; its interpretation however is subjective. An objective form of documentation is needed that will be simple, quick and inexpensive. To meet the challenge for the development of a skin colour code for Nigerians, a study was conducted at the University College Hospital (UCH) Ibadan, Nigeria. The study aimed at visually identifying possible skin colours and to reproduce this on the computer. 40 colour chips were identified and found relevant for the Negroid skin in Nigeria including the Nigerian albino. The chart can be laminated using thin transparent plastic film to prevent transmission of infection from skin to skin in different people. A skin colour code can be useful for clinical evaluation of disease conditions like vitiligo as well as for epidemiological studies. Its diagnostic potential is yet to be assessed. PMID- 17348749 TI - Health Worker Opinion/perception of health services provided to patients in the Selebi Phikwe Ni-Cu Mine Area, Botswana. AB - This study determines the prevalence of types of sicknesses and diseases affecting patients visiting health service facilities and the available health services within the Selebi Phikwe Ni-Cu mine area, Botswana. Through the administration of questionnaires and structured questions, attempts were made to establish and verify the existing human health problems at the study area by focusing on respiratory tract related symptoms of sicknesses and diseases. With the aid of statistical package for social sciences (SPSS), interpreted results from respondents indicated that all the health service providers served patients suffering from headaches, persistent coughing, chest pains, lower abdominal pains, pain when passing out urine, genital discharge and diarrhea. Seventy one percent of the health service providers indicated that their patients suffered from body weakness, 86 % indicated that they had patients who suffered from recent loss of body weight, and another 86 % pointed out that their patients had influenza/common cold. Other health complaints reported included unusual spitting, shortness of breath, palpitations, nausea/vomiting, diarrhoea, and constipation. Moreover the health service providers indicated that they had patients who suffered from significant illnesses of which some passed away. However if there are lacking facilities, patients are referred to bigger health service providers in the country. The findings of the study do not in general depict demarcating differences of health status of residents of the study area to those of the control site. A need therefore for further investigations to be conducted to establish relations of mining activities to human health at Selebi Phikwe is called for. PMID- 17348750 TI - Characteristics of hearing-impairment among patients in Ghana. AB - The causes, and characteristics of hearing-impairment were determined prospectively among six thousand, four hundred and twenty-eight (6,428) patients who reported at the Komfo Anokye Teaching Hospital (KATH) with hearing problems. The purpose of the study was to determine the characteristics and some causes of hearing loss of patients who report for management at Komfo Anokye Teaching Hospital. The procedure adopted included a detailed case history, Otoscopy and Pure-tone Audiometry. Of the 6,428 patients, 5,734 (89.9 %) were diagnosed as having significant hearing loss. There were more hearing impaired women than men at all ages. Majority of the patients had mild hearing loss. The overall prevalence of Sensorineural Hearing Loss was more in worse ear than better ear. Again, the occurrence of Sensorineural Hearing Loss was more than other types of hearing loss. Noise, Fever, Presbycusis, Sickness, Meningitis and Meniere's diseases were the major causes of Sensorineural Hearing Loss. Conductive Hearing Loss was attributed in the main to Wax, Foreign Bodies, Otitis Media, and Traumas. These findings have important implications on the need of resources for rehabilitation. PMID- 17348751 TI - Retinoblastoma--a clinico-pathological study in Ilorin, Nigeria. AB - Retinoblastoma is the commonest childhood primary malignant intraocular neoplasm that is often characterized by spontaneous regression. They display photoreceptor differentiation. This study provides the clinical presentations and histological profiles of retinoblastoma in Ilorin, Kwara-State, in the North Central geo political zone of Nigeria. A retrospective study of clinically and histologically verified retinoblastoma at the University of Ilorin Teaching Hospital, Ilorin, Kwara-State, Nigeria from January 1989 to December 2000 was undertaken. The clinical and histological features were analyzed using the patient's case folder and surgical pathology records. There were 20 patients, 9 males and 11 females (M:F ratio 1: 1.2), age range from 5 (1/2) months to 6 years with 23 eyeball tumours histologically confirmed retinoblastoma during the study period. Proptosis with chemosis was the most common clinical presentation (84.6 %). Bilaterality was 15 % in this study. Enucleation and Exenteration combined with chemotherapy were offered to 15 (75 %) and 5 (25 %) patients respectively. A poorly differentiated type with extensive areas of tumour necrosis was the commonest histological pattern. Thirteen (65 %) of the patients died before completing the course of chemotherapy. PMID- 17348752 TI - Shortage of health workers in the Malawian public health services system: how do parliamentarians perceive the problem? AB - The quality and quantity of health care services delivered by the Malawi public health system is severely limited, due to, among other things the shortage of adequate numbers of trained health care workers. In order to suggest policy changes and implement corrective measures, there may be need to describe the perceptions of the legislature on how they perceive as the cause of the problem, which could be the solutions and an evaluation of those solution. In this paper, I present the finding from a qualitative study of Hansards (official verbatim record of parliamentary speeches) analysed by discourse analysis. Parliamentarians identified the shortage of health workers as resulting from death, retirement and brain drain to other countries mostly the UK, Saudi Arabia and South Africa. Training more health workers, training new but lower cadres of health workers not marketable to the outside world, improving the working conditions and remuneration of health workers are suggested as some of the solutions. Even without the brain drain of health workers to other countries, Malawi's health sector personnel numbers are not adequate to serve the needs of the country. Relying on training more health workers in the numbers normally produced from the prevailing training institutions is unlikely to remove the shortages. PMID- 17348753 TI - Serological survey of antibodies to Toxoplasma gondii. AB - Toxoplasmosis is one of the most prevalent parasitic infections of man and livestock, and its transmission has usually been attributed to ingestion of undercooked or raw meat from infected livestock, with the infection rate in those animals being an important risk predictor of human disease, high in Iran and Ardabil State. During a study on this public health problem, we tested serum samples from cattle, goats, sheep and chicken from the State of Ardabil, Iran, for IgG antibodies to Toxoplasma gondii by enzyme-linked immunosorbent assay (ELISA). Antibodies to Toxoplasma gondii were found in 30 % (60 / 200) of sheep, 15 % (30 / 200) of goats and 9 %(18 / 200) of cattle, and none were found in chicken sera. Despite the differences in feeding habits of each species, the rate of infection of the animals tested could be attributed to livestock management methods, whose improvement could reduce infection. PMID- 17348754 TI - A two-pronged approach in leishmaniasis drug development in Kenya Medical Research Institute. PMID- 17348755 TI - Determinants of social inequalities in child mortality in Mozambique: what do we know? What could be done? AB - Health inequalities are no longer an issue only for developed countries. In recent years there is agreement that all countries present health inequalities regardless of their level of wealth. In low-income countries and especially in sub-Saharan Africa where the majority of the poor people live as well as their children, research on child health inequalities is still scarce. This review of evidence suggests that if Mozambique is to achieve the millennium development goals (MDGs) by 2015 further research on important determinants of disparities in child mortality is urgently needed. PMID- 17348756 TI - Using embedded music therapy interventions to support outdoor play of young children with autism in an inclusive community-based child care program. AB - For young children with autism enrolled in community-based inclusive child care programs, outdoor play can be a major challenge. The aim of this music therapy intervention was to improve peer interactions and meaningful play on the playground for four boys with autism by adding an outdoor music center and using original songs composed for each participant. A collaborative approach was used to support the implementation of the intervention by the children's teachers, engaging classroom peers as formal and informal helpers. The effects of the interventions were examined using a multiple baseline design with four conditions replicated across the four children. The results indicate that the musical adaptation of the playground itself did not improve social interactions of children with autism significantly, but it facilitated their play and involvement with peers by attraction to the sound and opportunity to use the instruments. The song interventions produced desirable peer interaction outcomes, and the collaborative consultative approach enabled teachers to implement interventions successfully in ongoing playground routines. In addition, peer-mediated strategies increased peer interactions and meaningful play on the playground. PMID- 17348757 TI - An experimental investigation of the effects of preferred and relaxing music listening on pain perception. AB - This study investigates the effects of music listening on perception and tolerance of experimentally induced cold pressor pain. Fifty-four participants (34 females, 20 males) each underwent 3 cold pressor trials while listening to (a) white noise, (b) specially designed relaxation music, and (c) their own chosen music. Tolerance time, pain intensity on visual analog scale, and the pain rating index of the McGill Pain Questionnaire and perceived control over the pain were measured in each condition. While listening to their own preferred music, male and female participants tolerated the painful stimulus significantly longer than during both the relaxation music and control conditions. However, only female participants rated the intensity of the pain as significantly lower in the preferred music condition. Both male and female participants reported feeling significantly more control when listening to their preferred music. It is suggested that personal preference is an influential factor when considering the efficacy of music listening for pain relief. PMID- 17348758 TI - Long-term effects of music therapy on elderly with moderate/severe dementia. AB - Over a period of 2 years we assessed the long-term effects of group music therapy carried out once weekly on the elderly (mean age: 83 years) suffering from moderate or severe dementia by observing changes in the cortisol level in saliva and in blood pressure and by an intelligence assessment. Systolic blood pressure determined 1 and 2 years after the start of therapy increased significantly in the nonmusic therapy group compared with that in music therapy group (p < .05). Systolic blood pressure increases with aging; the systolic blood pressure was significantly lower in participants who received music therapy. No significant differences in cortisol level in saliva or intelligence assessment score were observed, but the music therapy group maintained their physical and mental states during the 2-year period better than the nonmusic therapy group. This result indicates the lasting effect of once-a-week continuous music therapy. Even the elderly with moderate or severe dementia were able to participate in the group music therapy, and results suggest that enjoying singing and playing musical instruments in a concert was effective in preventing cardiac and cerebral diseases. PMID- 17348759 TI - The use of control groups in music therapy research: a content analysis of articles in the Journal of Music Therapy. AB - The use of a control group is fundamental to experimental research design, though the use with clinical populations must be carefully considered. The purpose of this research was to examine the use of control groups in research with clinical and nonclinical populations published in Journal of Musical Therapy from 1964 through 2004. Criteria for inclusion were music or music therapy as an independent variable applied to one or more groups and at least one control group that did not receive a music treatment. Control groups were qualified as alternative treatment, placebo, no contact, and treatment as usual. Of the 692 articles, 94 met these criteria, 62 clinical and 32 nonclinical, representing 13.5% of the publications. Results indicated that research with clinical populations involved a mean of 38.1 subjects typically divided into two groups, an experimental and a control group. The pretest-posttest design was the most common (55%) as was a treatment as usual control group (45%). These design methods maximized the impact of the experimental music treatment on outcome. Experimental music groups significantly improved over control groups in the vast majority of studies identified. Undoubtedly, the foundation for evidence-based clinical practice is firm. PMID- 17348760 TI - Predictive utility of the Computer-based Music Perception Assessment for Children (CMPAC). AB - A Computer-based Music Perception Assessment for Children (CMPAC) was designed and administered to 49 children (31 elementary school children; 18 hospitalized children) for the purpose of field testing and standardization. CMPAC is conceptualized as an assessment tool that yields information important to music therapists regarding children's listening and musically-related behavior: These behaviors include information on music choices and the effect of music on behavior (e.g., spontaneous singing or movement). The assessment involves children "clicking on" pictures that represent genres of children's music and listening to brief musical excerpts. Musical genres on CMPAC included songs from Sesame Street, the Animaniacs, Hap Palmer, Barney, and Disney. As part of the assessment, CMPAC generates three types of data about a child's listening behaviors: (a) the frequency with which the child listens to specific songs; (b) the duration of time the child spends listening to music; and (c) the order (or chronology) in which the child listens to specific songs. Additionally, the music therapist administering CMPAC records descriptive observations of the child's listening behavior (e.g., the child sings along to the music, the child moves during music listening, the child appears easily distracted by noises/activities in the hall, the child indiscriminately clicks [or repeatedly clicks] on a picture of music without attending to the music, etc.). Data obtained from field testing and from the clinical dispositions of 10 music therapists examining data output was subjected to statistical analysis in order to determine the predictive utility of CMPAC. Results suggest that CMPAC is a useful and valid assessment for assisting music therapists in making referral decisions for hospitalized children. PMID- 17348761 TI - Introduction: new directions in the treatment of atypical depression. PMID- 17348762 TI - A history of the concept of atypical depression. AB - The term atypical depression as a preferentially monoamine oxidase inhibitor (MAOI)-responsive state was first introduced by West and Dally in 1959. Further characterization of this syndrome and its responsiveness to antidepressants came to occupy the attention of many psychopharmacologists for the next 30 years. Different portrayals of atypical depression have emerged, for example, nonendogenous depression, phobic anxiety with secondary depression, vegetative reversal, rejection-sensitivity, and depression with severe chronic pain. Consistency across or within types has been unimpressive, and no coherent single type of depression can yet be said to be "atypical." In successfully demonstrating superiority of MAOI drugs to tricyclics, the Columbia (or DSM-IV) criteria have established their utility and become widely adopted, but other criteria have also passed this test. In this "post-MAOI" era, no novel compound or group of drugs has been clearly shown to have good efficacy in atypical depression, leaving the treatment of atypical depression as an unmet need. PMID- 17348763 TI - Atypical depression: a valid subtype? AB - The concept of atypical depression has evolved over the past several decades, yet remains inadequately defined. As currently defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV TR), the main criterion of atypical depression is the presence of mood reactivity in combination with at least 2 of 4 secondary criteria (hypersomnia, hyperphagia and weight gain, leaden paralysis, and oversensitivity to criticism and rejection). The focus on mood reactivity as the primary distinguishing criterion remains questionable among researchers who have been unable to verify the primacy of this symptom in relation to the other diagnostic criteria for atypical depression. A model challenging the DSM-IV-TR definition of atypical depression has been developed, redefining the disorder as a dimensional nonmelancholic syndrome in which individuals with a personality subtype of "interpersonal rejection sensitivity" have a tendency toward the onset of anxiety disorders and depression, thereby exhibiting a variety of dysregulated emotional and self consolatory responses. This reformulated definition of atypical depression (in arguing for the primacy of a personality style or rejection sensitivity as against mood reactivity) may lead to a better understanding and recognition of the disorder and its symptoms as well as other "spectrum" disorders within the scope of major depression. PMID- 17348764 TI - Treating depression with atypical features. AB - Depression with atypical features was first recognized in a subset of patients with depression who preferentially responded to the monoamine oxidase inhibitor (MAOI) phenelzine, in contrast to patients with melancholic depression. This article reviews the history of approaches in treating depression with atypical features. Initial studies in the early 1980s focused on phenelzine, but an unfavorable adverse effect profile limits its clinical use. Despite such difficulties, phenelzine remains the gold standard in eliciting high response rates in nearly two thirds of patients with atypical depression. Searches for agents with improved safety profiles led to studies of tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), chromium, and cognitive therapy approaches. Of these, TCAs showed inferior efficacy to MAOIs but also had cumbersome adverse effects. SSRIs have reported efficacy, but a lack of direct comparative studies limits clinical decision making. Cognitive strategies have shown promise, but demonstrating efficacy in comparison with an MAOI and placebo is limited to a single study. Despite advances in agents for melancholic depression, treatment for atypical depression remains dependent upon older agents for the greatest efficacy. PMID- 17348765 TI - Translating the evidence on atypical depression into clinical practice. AB - Although the introduction of selective serotonin reuptake inhibitors ushered in an era of relative comfort among clinicians in treating major depressive disorder (MDD), no one antidepressant is appropriate for all patients with depression. In patients with atypical symptoms, efficacy of therapeutic agents may be greatest for monoamine oxidase inhibitors (MAOIs). The first-generation MAOIs such as phenelzine and isocarboxazid were largely nonselective inhibitors of both subtypes of MAO, MAO(A) and MAO(B). These medications carried with them dietary restrictions, medication restrictions, a need for titration, and a substantial side effect burden, including weight gain, cardiovascular effects (i.e., hypertension and hypotension), and sexual side effects. The second-generation MAOI selegiline is selective for MAO(B) at oral doses of up to 10 mg/day. At higher doses, selegiline loses selectivity and inhibits both MAO(A) and MAO(B). Because the antidepressant effects of selegiline occur with the higher doses that impact tyramine pressor effects, an ideal formulation would optimize dose while minimizing adverse effects of MAO(A) inhibition in the gastrointestinal mucosa. Efforts in this direction led to formulation of the selegiline transdermal system (STS). The most common side effects are irritation at the patch site and insomnia. Drugs to be avoided with the STS include some pain medications, antidepressants, muscle relaxants, and any form of sympathomimetic amines, which include amphetamines, cold products with pseudoephedrine, phenylephrine, phenylpropanolamine, ephedrine, and stimulant-containing weight-reduction agents. Although no tyramine-restricted diet is required for the 6-mg/24-hour patch, a restricted diet is recommended for the higher-dose patches to reduce the risk of hypertensive crisis. PMID- 17348766 TI - Synergies between intrinsic and synaptic plasticity mechanisms. AB - We propose a model of intrinsic plasticity for a continuous activation model neuron based on information theory. We then show how intrinsic and synaptic plasticity mechanisms interact and allow the neuron to discover heavy-tailed directions in the input. We also demonstrate that intrinsic plasticity may be an alternative explanation for the sliding threshold postulated in the BCM theory of synaptic plasticity. We present a theoretical analysis of the interaction of intrinsic plasticity with different Hebbian learning rules for the case of clustered inputs. Finally, we perform experiments on the "bars" problem, a popular nonlinear independent component analysis problem. PMID- 17348767 TI - Distinguishing causal interactions in neural populations. AB - We describe a theoretical network analysis that can distinguish statistically causal interactions in population neural activity leading to a specific output. We introduce the concept of a causal core to refer to the set of neuronal interactions that are causally significant for the output, as assessed by Granger causality. Because our approach requires extensive knowledge of neuronal connectivity and dynamics, an illustrative example is provided by analysis of Darwin X, a brain-based device that allows precise recording of the activity of neuronal units during behavior. In Darwin X, a simulated neuronal model of the hippocampus and surrounding cortical areas supports learning of a spatial navigation task in a real environment. Analysis of Darwin X reveals that large repertoires of neuronal interactions contain comparatively small causal cores and that these causal cores become smaller during learning, a finding that may reflect the selection of specific causal pathways from diverse neuronal repertoires. PMID- 17348768 TI - Model selection for convolutive ICA with an application to spatiotemporal analysis of EEG. AB - We present a new algorithm for maximum likelihood convolutive independent component analysis (ICA) in which components are unmixed using stable autoregressive filters determined implicitly by estimating a convolutive model of the mixing process. By introducing a convolutive mixing model for the components, we show how the order of the filters in the model can be correctly detected using Bayesian model selection. We demonstrate a framework for deconvolving a subspace of independent components in electroencephalography (EEG). Initial results suggest that in some cases, convolutive mixing may be a more realistic model for EEG signals than the instantaneous ICA model. PMID- 17348769 TI - Information and topology in attractor neural networks. AB - A wide range of networks, including those with small-world topology, can be modeled by the connectivity ratio and randomness of the links. Both learning and attractor abilities of a neural network can be measured by the mutual information (MI) as a function of the load and the overlap between patterns and retrieval states. In this letter, we use MI to search for the optimal topology with regard to the storage and attractor properties of the network in an Amari-Hopfield model. We find that while an optimal storage implies an extremely diluted topology, a large basin of attraction leads to moderate levels of connectivity. This optimal topology is related to the clustering and path length of the network. We also build a diagram for the dynamical phases with random or local initial overlap and show that very diluted networks lose their attractor ability. PMID- 17348770 TI - Connection topology selection in central pattern generators by maximizing the gain of information. AB - A study of a general central pattern generator (CPG) is carried out by means of a measure of the gain of information between the number of available topology configurations and the output rhythmic activity. The neurons of the CPG are chaotic Hindmarsh-Rose models that cooperate dynamically to generate either chaotic or regular spatiotemporal patterns. These model neurons are implemented by computer simulations and electronic circuits. Out of a random pool of input configurations, a small subset of them maximizes the gain of information. Two important characteristics of this subset are emphasized: (1) the most regular output activities are chosen, and (2) none of the selected input configurations are networks with open topology. These two principles are observed in living CPGs as well as in model CPGs that are the most efficient in controlling mechanical tasks, and they are evidence that the information-theoretical analysis can be an invaluable tool in searching for general properties of CPGs. PMID- 17348772 TI - A maximum-likelihood interpretation for slow feature analysis. AB - The brain extracts useful features from a maelstrom of sensory information, and a fundamental goal of theoretical neuroscience is to work out how it does so. One proposed feature extraction strategy is motivated by the observation that the meaning of sensory data, such as the identity of a moving visual object, is often more persistent than the activation of any single sensory receptor. This notion is embodied in the slow feature analysis (SFA) algorithm, which uses "slowness" as a heuristic by which to extract semantic information from multidimensional time series. Here, we develop a probabilistic interpretation of this algorithm, showing that inference and learning in the limiting case of a suitable probabilistic model yield exactly the results of SFA. Similar equivalences have proved useful in interpreting and extending comparable algorithms such as independent component analysis. For SFA, we use the equivalent probabilistic model as a conceptual springboard with which to motivate several novel extensions to the algorithm. PMID- 17348773 TI - An augmented extended Kalman filter algorithm for complex-valued recurrent neural networks. AB - An augmented complex-valued extended Kalman filter (ACEKF) algorithm for the class of nonlinear adaptive filters realized as fully connected recurrent neural networks is introduced. This is achieved based on some recent developments in the so-called augmented complex statistics and the use of general fully complex nonlinear activation functions within the neurons. This makes the ACEKF suitable for processing general complex-valued nonlinear and nonstationary signals and also bivariate signals with strong component correlations. Simulations on benchmark and real-world complex-valued signals support the approach. PMID- 17348774 TI - Equilibria of iterative softmax and critical temperatures for intermittent search in self-organizing neural networks. AB - Kwok and Smith (2005) recently proposed a new kind of optimization dynamics using self-organizing neural networks (SONN) driven by softmax weight renormalization. Such dynamics is capable of powerful intermittent search for high-quality solutions in difficult assignment optimization problems. However, the search is sensitive to temperature setting in the softmax renormalization step. It has been hypothesized that the optimal temperature setting corresponds to the symmetry breaking bifurcation of equilibria of the renormalization step, when viewed as an autonomous dynamical system called iterative softmax (ISM). We rigorously analyze equilibria of ISM by determining their number, position, and stability types. It is shown that most fixed points exist in the neighborhood of the maximum entropy equilibrium w= (N(-1), N(-1), ..., N(-1)), where N is the ISM dimensionality. We calculate the exact rate of decrease in the number of ISM equilibria as one moves away from w. Bounds on temperatures guaranteeing different stability types of ISM equilibria are also derived. Moreover, we offer analytical approximations to the critical symmetry-breaking bifurcation temperatures that are in good agreement with those found by numerical investigations. So far, the critical temperatures have been determined only by trial-and-error numerical simulations. On a set of N queens problems for a wide range of problem sizes N, the analytically determined critical temperatures predict the optimal working temperatures for SONN intermittent search very well. It is also shown that no intermittent search can exist in SONN for temperatures greater than one-half. PMID- 17348777 TI - Variational Bayes solution of linear neural networks and its generalization performance. AB - It is well known that in unidentifiable models, the Bayes estimation provides much better generalization performance than the maximum likelihood (ML) estimation. However, its accurate approximation by Markov chain Monte Carlo methods requires huge computational costs. As an alternative, a tractable approximation method, called the variational Bayes (VB) approach, has recently been proposed and has been attracting attention. Its advantage over the expectation maximization (EM) algorithm, often used for realizing the ML estimation, has been experimentally shown in many applications; nevertheless, it has not yet been theoretically shown. In this letter, through analysis of the simplest unidentifiable models, we theoretically show some properties of the VB approach. We first prove that in three-layer linear neural networks, the VB approach is asymptotically equivalent to a positive-part James-Stein type shrinkage estimation. Then we theoretically clarify its free energy, generalization error, and training error. Comparing them with those of the ML estimation and the Bayes estimation, we discuss the advantage of the VB approach. We also show that unlike in the Bayes estimation, the free energy and the generalization error are less simply related with each other and that in typical cases, the VB free energy well approximates the Bayes one, while the VB generalization error significantly differs from the Bayes one. PMID- 17348778 TI - Emergency Department care of women experiencing intimate partner violence: are we doing all we can? AB - A significant proportion of Australian women experience intimate partner violence (IPV), many of them unidentified and thus not necessarily supported when they seek assistance in Emergency Departments. This article reviews the literature on IPV with a view to establishing the extent of the problem and the cost of IPV to the women, their families and the community. Electronic databases were searched using the keywords 'intimate partner violence', 'domestic violence', 'nursing' and 'emergency department'. The information obtained may inform health care professionals and assist with management, in the Emergency Department, of those who have experienced IPV. We explore the influence and impact of different types of care on women and the way women understand their experiences of care. From this review the following issues were identified as requiring further investigation: 1. the need to understand IPV from the women's perspective; 2. the factors influencing disclosure to ED staff; and 3. the type and consequent impact of care received in the ED. PMID- 17348780 TI - The impact of progress toward a Clinical Development Unit in Cardiology. AB - Health care organisations are continually implementing quality initiatives to develop staff to enhance the provision of patient care. However, the impact of such initiatives often fail to be assessed which can jeopardise provision for their systematic support. This paper reviews staff perceptions of how progress toward a Clinical Development Unit has influenced their practice in Cardiology. The process began in August 2003 when the unit philosophy included the use of best evidence into practice. Key initiatives integral to the development of a CDU were: facilitated engagement with clinical evidence, assisted through a structured education program for all staff; and opportunities for involvement in patient centred research. This evaluation sought descriptive information from staff as sustainability of such units is reliant on positive attitudes. Feedback was obtained from a convenience sample of staff who participated in three focus groups conducted over two months, 29 staff in total. Prevailing themes that emerged indicated the development of a positive ward culture. Four dominant themes emerged: the development of a culture of evidence into practice; a continuous learning environment; awareness of the contribution of research; and a re-focus on patient care. While structures and processes were in place to support learning and practices based in evidence that staff viewed favourably, there was little indication of individual staff members being 'pro-active' and being initiators of seeking evidence to make changes to practice. PMID- 17348779 TI - Admission and discharge practices: High Dependency Unit audit outcome. AB - This paper presents the findings of a retrospective audit of admission and discharge practices of a nurse led High Dependency Unit (Nurse Specials Unit) in Perth, Western Australia. The aim of the study was: to review the effectiveness of the inclusion and exclusion guidelines for patients admitted to the Nurse Special Unit (NSU); to identify characteristics of admitted patients; and to determine the level of adherence to admission protocols for documentation of patient condition, plan of care, medical and Clinical Nurse Consultant review. The sample comprised all patients admitted to the NSU from September 2004 - March 2005, excluding those (50) in the pilot study (n = 154). This audit revealed patients were primarily elderly and admitted for close nursing supervision. Inclusion and exclusion criterion were adhered to, however documentation of patient data, in relation to current status and plan of care, was poorly completed and frequently absent during intra hospital transfer. This lack of clear documentation poses a significant risk to the patient. Further research is required to determine strategies that result in appropriate and useful transfer documentation. In addition, the content of transfer data that permits continuity of care needs to be determined. PMID- 17348781 TI - Telling stories: nurses, politics and Aboriginal Australians, circa 1900-1980s. AB - The focus of this paper is stories by, and about, (mainly non-Aboriginal) Registered Nurses working in hospitals and clinics in remote areas of Australia from the early 1900s to the 1980s as they came into contact with, or cared for, Aboriginal people. Government policies that controlled and regulated Aboriginal Australians provide the context for these stories. Memoirs and other contemporary sources reveal the ways in which government policies in different eras influenced nurse's attitudes and clinical practice in relation to Aboriginal people, and helped institutionalise racism in health care. Up until the 1970s, most nurses in this study unquestioningly accepted firstly segregation, then assimilation policies and their underlying paternalistic ideologies, and incorporated them into their practice. The quite marked politicisation of Aboriginal issues in the 1970s in Australia and the move towards self-determination for Aboriginal people politicised many - but not all - nurses. For the first time, many nurses engaged in a robust critique of government policies and what this meant for their practice and for Aboriginal health. Other nurses, however, continued as they had before - neither questioning prevailing policy nor its effects on their practice. It is argued that only by understanding and confronting the historical roots of institutional racism, and by speaking out against such practices, can discrimination and racism be abolished from nursing practice and health care. This is essential for nursing's current and future professional development and for better health for Aboriginal Australians. PMID- 17348782 TI - Lights in the shadows: Florence Nightingale and others who made their mark. AB - Florence Nightingale, the 'lady with the lamp' became the image of 'heroic womanhood' (Bostridge 2004) when she returned from the Crimean War an iconic figure and ever since she has remained fated to wear the mantel of nursings' leading light. But she wasn't the only woman who made their mark or who undertook to risk their live caring for the sick and injured, wounded and dying in the Crimea. Sadly, Nightingale's iconic status has also succeeded in overshadowing the existence and the achievements of the many others who nursed during the Crimean war. These women, nuns, ordinary nurses, lady volunteers and others, working in Nightingale's shadow, contributed much to the comforts of the wounded and dying and this article seeks to illuminate their presence and contribution. It also highlights other aspects of Nightingale's work and in doing so, allows us to look into the shadows and shed more light on the others who were also there. PMID- 17348783 TI - A critical analysis of video tapes on postnatal depression. AB - AIM: To watch videos on postnatal depression which are used by professionals, mothers and voluntary agencies and to review their quality, content, and themes. BACKGROUND: To our knowledge there have been no previous studies of video tapes on postnatal depression for use by mothers and health care professionals during the antenatal and postnatal periods. A core group, consisting of a psychiatrist, health visitor and a mother, watched videos produced in the English language from Australia, South Africa, United States of America (USA) and the United Kingdom (UK). We found a similarity in all video tapes reviewed with regard to the feelings expressed by mothers and fathers. However, some of the context and culture differed in several countries where, during the management and treatment of postnatal depression, a medical rather than social model was preferred. PMID- 17348784 TI - The nature and impact of incontinence in men who have undergone prostate surgery and implications for nursing practice. AB - AIM: The aim of this study was to increase knowledge and understanding of the nature and experiences of incontinence in men one or more years post prostate surgery. METHODS: This descriptive study used a sample of convenience. Two hundred and twelve male participants who had undergone prostate surgery more than a year ago were asked about their experiences of incontinence. Participants were asked to fill in two questionnaires: The Expanded Prostate Cancer Index Composite and the Incontinence Impact Questionnaire. Participants were also asked about their prostate surgery, their health seeking behaviour in relation to incontinence, the type of discharge information they were given, and demographic information. RESULTS: Sixty-six percent of participants indicated that, in the last four weeks, their overall urinary function had been a problem and 36.3% reported their bowel habits were problematic, which affected the quality of their lives. In addition, 41% of participants reported that they were not given discharge information regarding the possibility of developing urinary incontinence and sexual problems post prostate surgery. CONCLUSIONS: Health care professionals should pay more attention to routinely providing information to all men regarding the possibility of developing incontinence or sexual problems post prostate surgery. This may assist them to better manage these problems. PMID- 17348785 TI - Masculinity and urogenital cancer: sensitive issues in health care. AB - The aim of this literature review was to analyse the approaches adopted by patients, health professionals, spouses and other care-givers towards sensitive issues related to male urogenital cancer, and to describe how these findings can be applied in health care practice. The findings revealed five identifiable domains, namely 'the barrier to talking', 'the barrier of sensitivity', 'the barrier of masculinity', 'the barrier to seeking health care' and 'the communicative barrier'. The conclusion was that the phenomenon of a barrier is strongly connected with hegemonic masculinity. The review of literature confirmed that, for many men, talking about genitally-related health problems is not easy and that health care professionals need to learn more about gender and masculinity in order to address urogenitally sensitive issues. PMID- 17348786 TI - Reflection on a critical incident. AB - Critical incidents are snapshots of something that happens to a patient, their family or nurse. It may be something positive, or it could be a situation where someone has suffered in some way (Rich & Parker 2001). Reflection and analysis of critical incidents is widely regarded as a valuable learning tool for nurses. The practice requires us to explore our actions and feelings and examine evidence based literature, thus bridging the gap between theory and practice (Bailey 1995). It also affords us the opportunity of changing our way of thinking or practicing, for when we reflect on an incident we can learn valuable lessons from what did and did not work. In this way we develop self-awareness and skills in critical thinking and problem solving (Rich & Parker 2001). The central aim of the following discussion is to explore and analyse an incident that occurred while attending a clinical placement at a hospital in rural New South Wales. To begin, the incident will be briefly described and the people involved introduced (The names of the people involved have been changed to protect their privacy). A wide range of literature will then be drawn upon in examining how this particular incident reflects specific Australian Nursing and Midwifery Council 'National Competency Standards for the Registered Nurse' (ANMC competencies). The outcome and implications for the writers' nursing practice will complete this reflection. PMID- 17348787 TI - Trying to make a difference: the Malawi experience of a Tuberculosis (TB) nurse specialist. AB - The incidence of Tuberculosis (TB) in the world is on the rise and is a major public health threat affecting a third of the world's population. TB is reportedly the second most common illness causing death in Sub-Saharan Africa, second only to HIV/AIDS. The developing world is most vulnerable, with factors like poverty, malnutrition, overcrowding, poor access to healthcare services and limited or lack of diagnostic facilities and trained healthcare personnel all compounding the extent of this global epidemic. While there may be many studies on medical management of the illness, there is very little understanding and lack of standardized terms, protocols and models of care that describe nurses' efforts in TB management. Thus, a study into factors that impact on nursing management of TB patients in Malawi and Australia was a quest to investigate the impact of nursing care on patients' well-being. It involved collecting data from Australia and Malawi to compare and contrast how different environments impinge on patients' care and outcomes. PMID- 17348796 TI - Redifferentiation of dedifferentiated bovine articular chondrocytes enhanced by cyclic hydrostatic pressure under a gas-controlled system. AB - Hydrostatic pressure is one of the most frequently used mechanical stimuli in chondrocyte experiments. A variety of hydrostatic pressure loading devices have been used in cartilage cell experiments. However, no gas-controlled system with other than a low pressure load was used up to this time. Hence we used a polyolefin bag from which gas penetration was confirmed. Chondrocytes were extracted from bovine normal knee joint cartilage. After 3 passages, dedifferentiated chondrocytes were applied to form a pellet. These pellets were cultured in chemically defined serum-free medium with ITS+Premix for 3 days. Then 5 MPa of cyclic hydrostatic pressure was applied at 0.5 Hz for 4 h per day for 4 days. Semiquantitative reverse transcriptase-polymerase chain reaction showed a 5 fold increase in the levels of aggrecan mRNA due to cyclic hydrostatic pressure load (p<0.01). Type II collagen mRNA levels were also upregulated 4-fold by a cyclic hydrostatic pressure load (p<0.01). Type I collagen mRNA levels were similarly reduced in the cyclic hydrostatic pressure load group and in the control group. The partial oxygen pressure (PO2) and partial carbon dioxide pressure (PCO2) of the medium in the bag reached equilibrium in 24 h, and no significant change was observed for 3 days afterwards. PO2 and PCO2 were very well controlled. The loaded pellet showed better safranin O/fast green staining than did the control pellet. Metachromatic staining by Alcian blue staining was found to be stronger in the loaded than in the control pellets. The extracellular matrices excretion of loaded pellets was higher than that of control pellets. These results suggest that gas-controlled cyclic hydrostatic pressure enhanced the cartilaginous matrix formation of dedifferentiated cells differentiated in vitro. PMID- 17348798 TI - The regenerative effects of platelet-rich plasma on meniscal cells in vitro and its in vivo application with biodegradable gelatin hydrogel. AB - The objective of the study was to test the hypothesis that platelet-rich plasma (PRP) enhances meniscal tissue regeneration in vitro and in vivo. In the in vitro study, monolayer meniscal cell cultures were prepared, and 3-(4,5-dimethylthiazol 2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt assay and 5-bromo-2'-deoxyuridine assay were performed to assess proliferative behavior in the presence of PRP. Alcian blue assay was performed to assess extracellular matrix (ECM) synthesis. To detect the fibrocartilage-related messenger ribonucleic acid (mRNA) expressions, real-time polymerase chain reaction was performed. In the in vivo study, 1.5-mm-diameter full-thickness defects were created in the avascular region of rabbit meniscus. Gelatin hydrogel (GH) was used as the drug delivery system for PRP growth factors. The defects were filled as follows: Group A, GH with PRP; Group B, GH with platelet-poor plasma; Group C, GH only. Each group was evaluated histologically at 4, 8, and 12 weeks after surgery. PRP stimulated deoxyribonucleic acid synthesis and ECM synthesis (p<0.05). Meniscal cells cultured with PRP showed greater mRNA expression of biglycan and decorin (p<0.05). Histological findings showed that remnants of gelatin hydrogels existed at 4 weeks, indicating that the hydrogels could control release for approximately 4 weeks. Histological scoring of the defect sites at 12 weeks revealed significantly better meniscal repair in animals that received PRP with GH than in the other two groups. These findings suggest that PRP enhances the healing of meniscal defects. PMID- 17348799 TI - Assessment of an automated bioreactor to propagate and harvest keratinocytes for fabrication of engineered skin substitutes. AB - Engineered skin substitutes (ESS) composed of autologous fibroblasts and keratinocytes attached to collagen-glycosaminoglycan (GAG) scaffolds are effective adjuncts in the treatment of massive burns. The Kerator, an automated bioreactor for keratinocyte culture, could hypothetically reduce labor and material requirements, and increase availability of ESS. Human keratinocytes were cultured in the Kerator and also in tissue-culture flasks. It was found that keratinocyte confluence increased exponentially with time in both the Kerator (r2=0.99) and the flasks (r2=0.96). Confluence (mean+/-SEM) of keratinocytes in the flasks (28+/-2.3%) was significantly higher than in the Kerator (18+/-0.93%) at day 4. However, there was no difference in confluence at harvest. The colony forming efficiency (CFE) and population doublings (PD) per day of keratinocytes harvested from the Kerator were 67+/-4.7% and 0.80+/-0.06, respectively, and were not different from the corresponding values for keratinocytes from flasks. ESS fabricated with keratinocytes from the Kerator or from the flasks were comparable in vitro in terms of histological anatomy, cellular viability, and surface hydration. These findings show that there are no differences between keratinocytes from the Kerator and those from the flasks regarding (a) growth to confluence, (b) CFE and growth rate (PD/day), or (c) quality of ESS in vitro, suggesting that the Kerator can automate fabrication of ESS and increase its availability for treatment of skin wounds. PMID- 17348800 TI - Preserve mesenchymal stem cell research. PMID- 17348801 TI - Heart development: the battle between mesoderm and endoderm. AB - Recent years have seen a surge of scientific research examining the interdependence of one germ layer in the development of the other, both in vivo and in vitro. For example, the endoderm is believed to play a crucial role in the formation of mesoderm and subsequent maturation of cells belonging to the mesodermal lineage. Our understanding of this complex relationship is continuously growing with reinterpretation of earlier concepts and apprehension of newer hypotheses into the biology of embryonic development. Here we discuss some of the events governing the cooperative control of endoderm over mesoderm, and propose a perspective based on the existing literature and our own experience. PMID- 17348802 TI - Mesenchymal stem cells: molecular targets for tissue engineering. AB - Mesenchymal stem cells (MSCs) represent an adherent, fibroblast-like population present not only in the bone marrow, but in a number of tissues, including blood, adipose tissue, muscle, and dermis. Their extensive proliferation and transdifferentiation potential makes them best suited for tissue engineering applications. Identification of growth factors and signaling pathways involved in self-renewal and differentiation is important for designing strategies to overcome replicative senescence and attain directed differentiation. Wnt, bone morphogenetic protein (BMP), and Notch pathways have been implicated to play key roles in self-renewal and differentiation of hematopoietic, intestinal, and epidermal stem cells. They are also involved in regulating MSC differentiation. However, MSC self-renewal has not received much attention, with Nucleostemin being the only recently identified proliferation molecule. Although immortalization using viral oncogenes and telomerase has been achieved, transformation in long-term cultures is a potential risk. Understanding of the mechanisms governing osteogenic differentiation of MSCs is expanding with the recent identification of two major transcription factors, Osterix and Runx2. Enhanced expansion as well as osteogenic differentiation of MSCs can be attained using a combinatorial approach involving co-expression of proliferation and differentiation genes. However, a thorough understanding of the molecular mechanism is necessary for enhancing the self-renewal ability and osteogenic potential in vitro. PMID- 17348803 TI - Transplantation of human undifferentiated embryonic stem cells into a myocardial infarction rat model. AB - Human embryonic stem (hES) cells hold great therapeutic potential for cell transplantation. To date, it remains uncertain whether undifferentiated hES cells can differentiate into cardiac lineage in vivo during myocardial infarction. Here we provide the first report that undifferentiated hES cells can survive in rat hearts during myocardial infarction without the formation of teratoma using undifferentiated green fluorescent protein (GFP)-transgenic hES cells. Using a laser-capture microscope to dissect the GFP-positive cell area from the hES injected hearts, we documented the expression of human cardiac-specific genes, including GATA-4, Nkx-2.5, and cardiac troponin I. Taken together, our results demonstrate that undifferentiated hES cells can be driven to the cardiac lineage under the local injured environment in the heart, which may provide a potential method for regenerating de novo myocardium to treat myocardial infarction. PMID- 17348804 TI - Intravenous delivery of autologous mesenchymal stem cells limits infarct size and improves left ventricular function in the infarcted porcine heart. AB - Systemic delivery of bone marrow-derived mesenchymal stem cells (MSCs) is a noninvasive approach for myocardial repair. We aimed to test this strategy in a pig model of myocardial infarction. Pigs (n = 8) received autologous MSCs (1 x 10(6)/kg body weight) labeled with fluorescent dye 48 h post proximal left anterior descending artery (LAD) occlusion. Hemodyamics, infarct size, and myocardial function were assessed at baseline and after 1 month. Morphologic analysis revealed that labeled MSCs migrated in the peri-infarct region, resulting in smaller infarct size (32 +/- 7 vs. 19 +/- 7%, p = 0.01), higher fractional area shortening (23 +/- 3 vs. 34.0 +/- 7%, p = 0.001), lower left ventricular end diastolic pressure (18.7 +/- 5 vs. 10.2 +/- 4 mmHg, p = 0.02) and higher +dp/dt (4,570 +/- 540 vs. 6,742 +/- 700 mmHg/s, p = 0.03) during inotropic stimulation. Systemic intravenous delivery of MSCs to pigs limits myocardial infarct size and is an attractive approach for tissue repair. PMID- 17348805 TI - Identification of cord blood-derived mesenchymal stem/stromal cell populations with distinct growth kinetics, differentiation potentials, and gene expression profiles. AB - Phenotypic heterogeneity has been observed among mesenchymal stem/stromal cell (MSC) populations, but specific genes associated with this variability have not been defined. To study this question, we analyzed two distinct isogenic MSC populations isolated from umbilical cord blood (UCB1 and UCB2). The use of isogenic populations eliminated differences contributed by genetic background. We characterized these UCB MSCs for cell morphology, growth kinetics, immunophenotype, and potential for differentiation. UCB1 displayed faster growth kinetics, higher population doublings, and increased adipogenic lineage differentiation compared to UCB2. However, osteogenic differentiation was stronger for the UCB2 population. To identify MSC-specific genes and developmental genes associated with observed phenotypic differences, we performed expression analysis using Affymetrix microarrays and compared them to bone marrow (BM) MSCs. We compared UCB1, UCB2, and BM and identified distinct gene expression patterns. Selected clusters were analyzed demonstrating that genes of multiple developmental pathways, such as transforming growth factor-beta (TGF-beta) and wnt genes, and markers of early embryonic stages and mesodermal differentiation displayed significant differences among the MSC populations. In undifferentiated UCB1 cells, multiple genes were significantly up-regulated (p < 0.0001): peroxisome proliferation activated receptor gamma (PPARG), which correlated with adipogenic differentiation capacities, hepatocyte growth factor (HGF), and stromal-derived factor 1 (SDF1/CXCL12), which could both potentially contribute to the higher growth kinetics observed in UCB1 cells. Overall, the results confirmed the presence of two distinct isogenic UCB-derived cell populations, identified gene profiles useful to distinguish MSC types with different lineage differentiation potentials, and helped clarify the heterogeneity observed in these cells. PMID- 17348806 TI - Rapid and efficient in vitro generation of pancreatic islet progenitor cells from nonendocrine epithelial cells in the adult human pancreas. AB - The absence of efficient and directed methods for the differentiation of adult pancreatic progenitor cell populations to pancreatic islet cells has raised doubts concerning the regeneration potential inherent in the adult pancreas. Relatively low levels of islet cell differentiation have been reported using adult pancreatic cells in vivo and in vitro. In the present study, we initially enriched for a nonendocrine epithelial component of the adult human pancreas and defined conditions that are permissive to islet cell differentiation in vitro. Sequential progression of cell differentiation in the permissive conditions allowed for incremental evaluation of changes occurring in the cell population. Optimization of the differentiation process, for the efficient production of islet endocrine cells, was accomplished by identifying specific factors and culture conditions that increased islet progenitor production 250-fold. Ultimately, 85% percent of the nonendocrine epithelial cells isolated from human pancreatic tissue and cultured in the optimized conditions for 8 days, readily re expressed pancreatic duodenal homeobox-1 (Pdx1). Sixty-five percent of these Pdx1 expressing cells were capable of additional islet endocrine cell differentiation. This represents a significant advancement in the differentiation of an adult pancreatic progenitor cell population in vitro and suggests that the nonendocrine compartment of the human pancreas remains an important cell resource for the generation of transplantable islets to treat diabetes. PMID- 17348807 TI - Phenotypical and functional characterization of freshly isolated adipose tissue derived stem cells. AB - Adipose tissue contains a stromal vascular fraction (SVF) that is a rich source of adipose tissue-derived stem cells (ASCs). ASCs are multipotent and in vitro expanded ASCs have the capacity to differentiate, into amongst others, adipocytes, chondrocytes, osteoblasts, and myocytes. For tissue engineering purposes, however, it would be advantageous to use the whole SVF, which can be transplanted without further in vitro selection or expansion steps. Because little is known about the freshly isolated ASCs in the SVF, we phenotypically characterized human freshly isolated ASCs, using flow cytometry. In addition, we investigated whether freshly isolated ASCs have functional properties comparable to cultured ASCs. For this, the differentiation potential of both freshly isolated ASCs and cultured ASCs into the osteogenic pathway was analyzed. Freshly isolated ASCs slightly differed in immunophenotype from cultured ASCs. Contrary to cultured ASCs, freshly isolated ASCs were shown to be highly positive for CD34, and positive for CD117 and HLA-DR. On the other hand, expression of CD105 and especially CD166 on the freshly isolated ASCs was relatively low. After osteogenic stimulation of freshly isolated ASCs, both Runx-2 and CollaI gene expression were significantly increased (p < 0.05). However, there was a difference in the kinetics of gene expression between freshly isolated and cultured ASCs and also between the different SVF isolates tested. There was no difference in alkaline phosphatase activity between freshly isolated ASCs and cultured ASCs. In addition, freshly isolated ASCs stained positive for osteonectin and showed matrix mineralization. We conclude that although there are minor differences in phenotype and kinetics of differentiation between freshly isolated ASCs and cultured ASCs, the use of freshly isolated ASCs for tissue engineering purposes involving bone repair is potentially applicable. PMID- 17348808 TI - Simplified protocol to isolate, purify, and culture expand mesenchymal stem cells. AB - Mesenchymal stem cells (MSCs) are widely used for experimental regenerative strategies. Due to their differentiation capacity into mesenchymal lineages, they are a potential cellular source for tissue regeneration. Because there is no specific antigen that can be used to define MSCs directly, there is no consensus about how to isolate them. Here we describe a simple protocol to isolate, purify, and culture expand murine bone marrow MSCs using magnetic cell sorting and plastic adherence. We further show that cytokine supplementation enhances MSC proliferation without jeopardizing their pluripotency. PMID- 17348809 TI - A method for single-cell sorting and expansion of genetically modified human embryonic stem cells. AB - Genetic modification of human embryonic stem (hES) cells is essential for studies of gene function and differentiation. The expression of transgenes may direct tissue-specific differentiation and aid in the identification of various differentiated cell types. Stable genomic integration of transgenes is optimal because hES cell differentiation can span several days to weeks and include numerous cell divisions, and establishing homogeneous modified cell lines will facilitate research studies. Herein we provide a method for producing and expanding hES cell lines from single cells that have been isolated by fluorescence-activated cell sorting (FACS) following genetic modification by lentivirus vectors. Using this method, we have established enhanced green fluorescent protein (eGFP)-expressing hES cell lines that are pluripotent, contain a diploid chromosomal content, and stably express eGFP following more than 2 months of routine culture and in vivo differentiation. PMID- 17348810 TI - Comprehensive analysis of chemotactic factors for bone marrow mesenchymal stem cells. AB - To understand which growth factors/cytokines can affect migration of mesenchymal stem cells (MSCs) to injured tissues, we compared the effects of many (26) growth factors/cytokines on the migration activity of rabbit and human MSCs using a microchemotaxis chamber. Among them, platelet-derived growth factor (PDGF)-BB, PDGF-AB, epidermal growth factor (EGF), HB-EGF, transforming growth factor (TGF alpha), insulin growth factor (IGF-I), hepatocyte growth factor (HGF), fibroblast growth factor (FGF-2), and thrombin consistently enhanced the migration of rabbit and human MSCs at appropriate concentrations. PDGF-BB showed the greatest effect on migration. Various combinations of these factors further enhanced the migration of MSCs, whereas combinations of factors that shared common cell surface receptors did not induce the additive stimulation. On the other hand, some combinations, including that of FGF-2 or thrombin with PDGF-BB, suppressed the migration activity of MSCs. These findings suggest that combinations of growth factors are important to eliciting the maximal chemotactic effect. The factors that induced the migration of MSCs also enhanced their proliferation, suggesting that migration and proliferation can take place simultaneously. The above factors were also effective in stimulating the migration of fibroblasts, but thrombin alone selectively enhanced the migration of MSCs, suggesting that thrombin is useful to stimulate migration of MSCs without migration of fibroblasts. PMID- 17348811 TI - Stage-dependent Olig2 expression in motor neurons and oligodendrocytes differentiated from embryonic stem cells. AB - Although embryonic stem (ES) cells are capable of forming any cell type in the body, the mechanisms that control cell type-specific differentiation are largely unknown. In the present study, we examined the process of differentiation to motor neurons and oligodendrocytes from mouse (Olig2GFP) ES cells. Mouse ES cells undergo a sequential process of differentiation over a 3-week period to generate motor neurons and oligodendrocytes. At day 7 of differentiation, Olig2-expressing cells are biased to a neuronal lineage. However, further differentiation (day 32) resulted in the majority of Olig2-expressing cells exhibiting an oligodendrocyte phenotype as well as a reduced ability to make motor neurons. Exposure of human ES cells to Sonic hedgehog (Shh) likewise resulted in enhanced motor neuron differentiation. Our results establish the requirements for directing ES cells to become motor neurons and oligodendrocytes and show that ES cell-derived Olig2 + cells can give rise to both motor neurons and oligodendrocytes, depending on the time at which differentiation is initiated. PMID- 17348812 TI - Transgenes delivered by lentiviral vector are suppressed in human embryonic stem cells in a promoter-dependent manner. AB - Lentiviruses have been increasingly used for genetic modification of human cells including embryonic stem (ES) cells. Using four ubiquitous promoters- cytomegalovirus (CMV), cytomegalovirus immediate-early enhancer/chicken beta actin hybrid (CAG), phosphoglycerate kinase (PGK), and human elongation factor 1alpha (EF1alpha)--in a lentiviral vector to drive the expression of the enhanced green fluorescent protein (EGFP) gene in human ES cells and mouse ES cells, we determined the extent of EGFP suppression by assessing the percentage of cells that were transduced with the EGFP gene but did not fluoresce green. A much higher level of transgene suppression was observed in human ES cells as compared to mouse ES cells. The suppression was also highly promoter dependent, leading to inactivation of more than 95% of the EGFP genes under the CMV or CAG promoter while only 55% under the PGK promoter. No promoter-dependent suppression was observed in transient transfection of human ES cells. Thus, the common phenomenon of poor transgene expression in human ES cells may be caused mainly by suppression of the transgene right after transduction and integration. Cautions should be taken to choose the optimal promoter when lentiviruses are used for genetic modification of human ES cells. PMID- 17348813 TI - Multiple unit HLA-unmatched sex-mismatched umbilical cord blood transplantation for advanced hematological malignancy. AB - We investigated the effect of multiple-unit umbilical cord blood (UCB) transplantation on engraftment in the setting of severe human leukocyte antigen (HLA) mismatch. Ten poor-risk adult patients with hematological malignancy received multiple unit, HLA-unmatched, sex-mismatched, unrelated UCB transplantation after a reduced intensity-conditioning regimen (RICR) with engraftment as the primary endpoint. The median age of the patients was 55 years with a range of 28-67. Patients received one unit of UCB per 10 kg of recipient body weight (5-7 units). The median number of nucleated cells and CD34(+) cells per kilogram of recipient body weight infused was 6.3 x 10(7) (range 3.8-10.0) (NC/kg) and 5.7 x 10(5) (range 1.1-11.9) (CD34/kg), respectively. Three patients expired before day 28 and were not evaluable for engraftment. Five of the remaining 7 patients showed increasing neutrophil counts. Fluorescent in situ hybridization (FISH) for the Y chromosome or HLA-typing showed only donor cells in the peripheral blood. After engraftment, HLA typing was done on 3 patients and their infused UCB units. All revealed the presence of a single HLA type concordant with one of the infused units. Moreover, the order of infusion did not influence which UCB unit engrafted. The engrafting UCB units were infused first or second in one case and fourth in the other two. One patient transplanted for refractory acute lymphoblastic leukemia (ALL) survives in continuous complete remission 4 years after transplant. He engrafted with one UCB unit, is fully hematologically reconstituted, has no evidence of graft-versus-host disease (GVHD), and takes no immunosuppressive medication. HLA typing reveals that the recipient and the engrafted cord blood match at only one HLA-B locus using conventional 6 antigen typing (A, B, and DR). Although engraftment was not accelerated, it did occur in the majority of evaluable patients. Long-term disease-free survivorship without debilitating GVHD is possible in patients with refractory hematological malignancy who receive unmatched multiple unit UCB. PMID- 17348815 TI - On the discovery of interferon. PMID- 17348816 TI - The role of IFN-alpha as homeostatic agent in the inflammatory response: a balance between danger and response? AB - Interferon-alpha (IFN-alpha) is thought of by most immunologists as a fundamental component of the antiviral innate immune response, with other, accessory properties. Several lines of evidence point to a fundamental reappraisal of this conceptual framework because it may neglect other crucial functions of this cytokine under both health and disease conditions. Among these, a regulatory role in the inflammatory response is probably of paramount importance, as shown by in vivo and in vitro studies on humans, pets, and farm and laboratory animals. This role would not conflict with the main functions of IFN-alpha in the innate immune system and would complement these in line with major, evolution-based needs of the host. A hinge role of IFN-alpha between innate and adaptive immunity was recognized in the past on the basis of compelling evidence. This concept should now be widened; not only does IFN-alpha act to trigger, amplify, and sustain the different phases of the immune response, but it could also promote a substantial balance between danger and inflammatory response when an infectious challenge is either declining or completely over. PMID- 17348817 TI - Secretion of cytokines in breast cancer cells: the molecular mechanism of procathepsin D proliferative effects. AB - Procathepsin D (pCD) is a major secreted protein in estrogen receptor-positive (ER+) breast cancer cell lines. Several independent studies have documented pronounced mitogenic effect of secreted pCD on cancer tissue-derived cell lines, including those from breast, lung, and prostate cancer. It has also been shown that the proliferative effect of pCD involves both autocrine and paracrine modes of action. Recent studies have suggested that pCD could act as a key paracrine communicator between cancer and stromal cells. We have shown earlier that the proliferative activity of pCD depends on the activation peptide sequence of pCD. The present study casts light on the mechanism by which pCD influences the proliferation of cancer cells expressing the ER. Results described in the current paper clearly show that pCD initiates secretion of cytokines interleukin-4 (IL 4), IL-8, IL-10, IL-13, macrophage inflammatory protein-1beta and (MIP-1beta) from such tumor cells. Secreted cytokines take part in the proliferation of the cancer cells, as proven by selective inhibition using antibodies. In addition, expression of cytokine receptors on tested cell lines corresponded to the effects of individual cytokines. An analogous pattern was also observed for fibroblasts, which, under physiologic conditions, are the cells in closest contact with the tumor tissue and play a role in tumor growth and invasion. Our observations were further supported by coculture experiments that are in agreement. Although very similar in response to addition of pCD, the invasive ER- cells do not secrete cytokines. Together with previous in vivo results, these data point to pCD as one of key molecules for therapeutic attack in breast cancer. PMID- 17348818 TI - Lamivudine and IFN-beta sequential therapy in HBe antigen-positive patients with chronic hepatitis B virus genotype C infection. AB - Sequential treatment with lamivudine and interferon (IFN) has induced sustained biochemical and virologic responses in the majority of patients with chronic hepatitis B in France. However, the efficacy of sequential treatment in patients with chronic hepatitis B virus (HBV) genotype C infection has not been evaluated. Twenty-four HBe antigen-positive patients were treated with 100 mg lamivudine alone for 16-32 weeks, then with both 6 MU IFN-beta and lamivudine for 4 weeks, and lastly with IFN-beta alone for 20 weeks. Sustained response was achieved in 7 (29%) patients 24 weeks after the end of therapy. No lamivudine-resistant variants emerged in any patient. Hepatitis flare occurred in 3 patients after the withdrawal of lamivudine, but none had decompensation. The patients with sustained response were significantly younger at baseline (p = 0.033) and had a significantly lower HBV DNA level at the start of IFN (p = 0.020) than those without sustained response. In conclusion, the rate of response to sequential therapy with lamivudine and IFN in HBe antigen-positive patients with HBV genotype C infection was lower than the rate reported previously. Patients who were young or who had a favorable virologic response to lamivudine were more likely to have a sustained response. PMID- 17348819 TI - Effects of IFN-gamma and Stat1 on gene expression, growth, and survival in non small cell lung cancer cells. AB - Stat transcription factors are activated by cytokines and can activate pathways important in oncogenesis. Although previous studies have identified an oncogenic role of Stat3 in lung cancer cells, the role of Stat1 is unclear. Using a mutant of Stat1 with constitutive activity (Stat1C), we examined the effect of persistent Stat1 activity on lung cancer cell growth, survival and gene expression. We identified no significant effect of Stat1C alone or with interferon-gamma (IFN-gamma) on lung cancer cell growth or survival. Consistent with prior reports, Stat1C expression alone elicited minimal changes in gene expression and required costimulatory IFN-gamma for full activity. Using oligonucleotide gene arrays and quantitative real-time PCR, we identified numerous proinflammatory gene products and chemokines regulated by IFN gamma/Stat1C signaling. These results suggest the major role of IFN-gamma and Stat1 in lung cells is to direct a proinflammatory gene expression program rather than have major effects on cell growth or survival or both. PMID- 17348820 TI - Cervical cytokine responses in women with primary or recurrent chlamydial infection. AB - Little is known about concurrent expression of cervical cytokines and their regulation by sex hormones during primary or recurrent chlamydial infections in humans. Cytokine (interleukin-1beta [IL-1beta], IL-6, IL-10, interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) concentrations in cervical washes and serum samples, along with levels of beta-estradiol and progesterone in women with primary or recurrent chlamydial infections and healthy controls, were measured by ELISA. Women with recurrent infections had significantly higher levels of IFN-gamma in cervical washes than did women with primary infections. Significant negative correlation was found between IL-1beta and progesterone levels during recurrent infections. Beta-estradiol levels in women with primary infections showed significant negative correlations with cervical concentrations of IL-10, IL-1beta, and IL-6. Our study suggests that Chlamydia trachomatis infection in the female genital tract may be regulated by both the synergistic actions of the cytokines and the sex hormones beta-estradiol and progesterone. PMID- 17348821 TI - Changes in serum and ascitic monocyte chemotactic protein-1 (MCP-1) and IL-10 levels in cirrhotic patients with spontaneous bacterial peritonitis. AB - Spontaneous bacterial peritonitis (SBP) is a prototypical infectious disease of cirrhotic patients. It has been suggested that cirrhotic patients' response to infection is less effective because of differences in the inflammatory and immune reactions. This study aimed to investigate the expression of the inflammatory cytokines monocyte chemotactic protein-1 (MCP-1) and interleukin-10 (IL-10) in cirrhotic patients with SBP. The MCP1 and IL-10 levels in the sera and ascitic fluids of cirrhotic patients with (n = 40) or without SBP (n=17) were serially analyzed by ELISA. In the non-SBP group, the mean MCP-1 levels in sera and ascites were 53.0 +/- 45.8 pg/mL and 197.5 +/- 109.5 pg/mL, respectively, and the IL-10 levels were 10.9 +/- 9.5 pg/mL and 77.6 +/- 79.7 pg/mL, respectively. In the SBP group, the mean MCP-1 levels in serum and ascites before treatment were 164.7 +/- 126.4 pg/mL and 365.3 +/- 583.0 pg/mL, respectively, and the IL-10 levels were 31.4 +/- 44.1 pg/mL and 188.1 +/- 189.5 pg/mL, respectively. The sera MCP-1 and ascites IL-10 levels differed significantly between the two groups. In the SBP group, sera and ascitic MCP-1 and IL-10 levels fell during treatment. The low MCP-1 and IL-10 levels on the seventh day of treatment were found to have a statistically significant relationship to patient survival. MCP-1 and IL-10 levels in sera and ascites may be related to the clinical course of SBP. PMID- 17348822 TI - Effects of IFN-alpha on alpha-fetoprotein expressions in hepatocellular carcinoma cells. AB - We investigated the effects of pegylated (PEG)-IFN-alpha2b on alpha-fetoprotein (AFP) expression as demonstrated by protein and mRNA levels in six human hepatocellular carcinoma (HCC) cell lines. The number of KIM-1 cells in culture with PEG-IFN-alpha2b decreased between 24 amd 240 h, whereas the levels of intracellular and secreted AFP per cellular protein increased (except at 192 h), with levels 1.9-fold and 2.9-fold higher at maximum, respectively, than cells without PEG-IFN-alpha2b (control). The mRNA level increased between 72 and 192 h, when the level was 3-fold higher than that of the control. In the 72-h culture with 40-5000 IU/mL PEG-IFN-alpha2b, there were dose-dependent increases in AFP protein and mRNA expression and dose-dependent decrease in cell number resulting from apoptosis and blockage of the cell cycle at the S-phase. The rate of fucosylated AFP in the cell lysate decreased in a dose-dependent and time dependent manner. In the PEG-IFN-alpha2b culture of the other five HCC cell lines, cell proliferation was suppressed, but the expressions of AFP protein and mRNA increased in only two cell lines, and suppression of cell proliferation was not related to the increase in AFP expressions. Our findings demonstrated that PEG-IFN-alpha2b induces an increase in AFP expression at both the protein and mRNA levels. PMID- 17348823 TI - Genetic polymorphisms of inflammatory cytokines and liver fibrosis progression due to recurrent hepatitis C. AB - To ascertain whether single nucleotide polymorphisms (SNPs) regulating the expression of interferon-gamma (IFN-gamma), IFN-gamma receptor-1 (IFNGR-1), interleukin-6 (IL-6), IL-10, IL-18, and tumor necrosis factor-alpha (TNF-alpha) may be associated with early fibrosis progression of recurrent hepatitis C, 50 liver transplantation recipients (32 men, 18 women, median age 56 years) with a median histologic follow-up time of 54 months were studied; 98 healthy blood donors served as controls. Cytokine SNPs were determined by means of previously described PCR-based methods. On the basis of the SNP studies, a low, intermediate, or high producer cytokine phenotype was attributed to each patient. Only 1 of the 17 low IL-10 producers reached an Ishak staging score > 2, in contrast to 20 of the 33 patients who were intermediate or high IL-10 producers (Mantel-Cox, p < 0.005). Recipients who were low IL-10 producers and high IFN gamma producers had significantly slower fibrosis progression in comparison to intermediate/high IL-10 producers and low IFN-gamma producers (p < 0.005). In conclusion, cytokine SNPs resulting in high and low producer phenotypes of both Th1 and Th2 cytokines appear to modulate the course of recurrent hepatitis C. Low IL-10 producers are those with the slowest histologic fibrosis progression. PMID- 17348825 TI - Acridine and acridone derivatives, anticancer properties and synthetic methods: where are we now? AB - Acridine derivatives are interesting chemotherapeutic agents that were first used as antibacterial and antiparasite agents. In this review we wish to concentrate our attention on the anticancer properties of acridines used in clinics since the 1970's. Based on recent results, an outlook on antitumour acridine chemotherapy will be proposed. The biological activity of acridines is mainly attributed to the planarity of these aromatic structures, which can intercalate within the double-stranded DNA structure, thus interfering with the cellular machinery. Recent understanding of the mode of action of acridines leads to continuous and exciting research in this heterocyclic family. Indeed, biological targets such as topoisomerases I and II, telomerase/telomere and protein kinases emerge and allow the design of novel acridine-based patterns. This review further pinpoints the latest progress in the development of anticancer agents based on naturally occurring and synthetic acridines (e.g. acridones, pyridoacridines); for this matter in vitro/in vivo studies and clinical trial results will be discussed. The DNA-affinic property of acridine is also useful to vectorise drugs into cell nuclei and some applications in hypoxia-selective treatment, platinum or N mustard derived conjugates will be reported. Some other properties including inhibition of multidrug resistance or potential impact on Alzheimer disease will be treated. It is noteworthy that the position and the nature of the substituent on the heterocyclic core are determinants for the biological property and selectivity observed. So, we wish also to disclose a summary of recent synthetic methodologies developed for acridine synthesis. PMID- 17348826 TI - In silico design of protein kinase inhibitors: successes and failures. AB - Protein kinases are among the most exploited targets in modern drug discovery due to key roles these enzymes play in human diseases including cancer. The in silico approach, an important part of rational design of protein kinase inhibitors, is founded on vast information about 3D structures of these enzymes. This review summarizes general structural features of the kinase inhibitors and the studies applied toward a large scale chemical database for virtual screening. Analyzed are the ways of validating the modern docking tools and their combinations with different scoring functions. In particular, we discuss the kinase flexibility as a reason for failures of the docking procedure. Finally, evidence is provided for the main patterns of kinase-inhibitor interactions and creation of the hinge region-directed 2D filters. PMID- 17348827 TI - Recent progress in discovery and development of antimitotic agents. AB - This review highlights structural diversity of antimitotic agents. In particular, we emphasized current antimitotic therapies based on modulation of microtubule dynamics. With several successful anticancer drugs on the market and numerous compounds in clinical developments, tubulin-binding agents remain among the most important categories of anticancer agents. Compounds targeting mitotic kinases and kinesins are also discussed. PMID- 17348828 TI - Meta-analysis of anticancer drug structures--significance of their polar allylic moieties. AB - This meta-analysis examines a wide range of small molecule anticancer drugs to search for a structure common to all. Although they encompass a very wide range of structures, nearly all reveal the presence of an allylic O, N, or S atom. In some, the allylic oxygen is a carbonyl group, or an alcohol group, which can be substituted (ester, lactone, glycoside, ether) or replaced by an amino or imino nitrogen Some antineoplastic drugs do not exhibit this moiety but are converted in vivo to allylic derivatives. An allylic hydroxyl is also present in most sphingolipids, ubiquitous body components that control proliferative and anti proliferative cell functions. Ceramide, the precursor of all the allylic sphingolipids, seems to be a general inducer of apoptosis in cancer cells. Further examination of sphingolipids and anticancer drugs shows the frequent occurrence of [i] double bonds conjugated to the allylic bond, (ii) two or more allylic moieties in each molecule, (iii) lipophilic features, especially linear chains, and (iv) attachment of an O, N, or S atom to a carbon atom of the allylic double bond, e.g., -CH(2)-C(OMe)=CH-CH(OH)-CH(2)-. Suggested mechanisms of action: (a) allylic ketone drugs undergo a Michael condensation with tumor thiols or other reactive groups; (b) allylic OH drugs undergo oxidation to an allylic ketone, generating reactive oxygen; (c) some interfere with mitochondrial ubiquinone, blocking ATP production; (d) some act as a ceramide mimic (inhibitor or agonist) in ceramide-controlled kinases, phosphatases, and proteases; (e) many antineoplastic drugs stimulate ceramide-forming processes. PMID- 17348829 TI - Vascular endothelial growth factor (VEGF) inhibition--a critical review. AB - Angiogenesis, or formation of new blood capillaries from preexisting vessels, plays both beneficial and damaging roles in the organism. It is a result of a complex balance of positive and negative regulators, and vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic factors involved in tumor angiogenesis. VEGF increases vascular permeability, which might facilitate tumor dissemination via the circulation causing a greater delivery of oxygen and nutrients; it recruits circulating endothelial precursor cells, and acts as a survival factor for immature tumor blood vessels. The endotheliotropic activities of VEGF are mediated through the VEGF-specific tyrosine-kinase receptors: VEGFR-1, VEGFR-2 and VEGFR-3. VEGF and its receptors play a central role in tumor angiogenesis, and therefore the blockade of this pathway is a promising therapeutic strategy for inhibiting angiogenesis and tumor growth. A number of different strategies to inhibit VEGF signal transduction are in development and they include the development of humanized neutralizing anti-VEGF monoclonal antibodies, receptor antagonists, soluble receptors, antagonistic VEGF mutants, and inhibitors of VEGF receptor function. These agents can be divided in two broad classes, namely agents designed to target the VEGF activity and agents designed to target the surface receptor function. The main purpose of this review is to summarize all the available information regarding the importance of the pro angiogenic factor VEGF in cancer therapy. After an overview of the VEGF family and their respective receptors, we shall focus our attention on the different VEGF-inhibitors existent nowadays. Agents based upon anti-VEGF therapy have provided solid proofs about their success, and therefore we believe that a critical review is of the utmost importance to help researchers in their future work. PMID- 17348830 TI - Antitumor carbazoles. AB - Natural and synthetic carbazoles, either in a pure substituted or in an annellated substituted form, represent an important and heterogeneous class of anticancer agents, which has grown considerably over the last two decades. Many carbazole derivatives have been tested for cyctotoxic activity, some of them have entered clinical trials, but only very few have been approved for the treatment of cancer so far, since the clinical application of many carbazoles has encountered problems like severe side effects or multidrug resistance. Due to their polycyclic, planar and aromatic structure carbazoles are predestined for intercalation into DNA and therefore DNA remains one of the main targets for cytotoxic carbazoles. For many carbazoles cytotoxicity can be related to DNA dependent enzyme inhibition such as topoisomerase I/II and telomerase. But also other targets such as cyclin-dependent kinases and estrogen receptors have emerged. PMID- 17348832 TI - Protein kinases as targets for antiparasitic chemotherapy drugs. AB - Parasitic protozoa infecting humans have a great impact on public health, especially in the developing countries. In many instances, the parasites have developed resistance against available chemotherapeutic agents, making the search for alternative drugs a priority. In line with the current interest in Protein Kinase (PK) inhibitors as potential drugs against a variety of diseases, the possibility that PKs may represent targets for novel anti-parasitic agents is being explored. Research into parasite PKs has benefited greatly from genome and EST sequencing projects, with the genomes from a few species fully sequenced (notably that from the malaria parasite Plasmodium falciparum) and several more under way, the structural features that are important to design specific inhibitors against these PKs will be reviewed in the present work. PMID- 17348833 TI - Enoyl reductases as targets for the development of anti-tubercular and anti malarial agents. AB - Tuberculosis (TB) and Malaria are neglected diseases, which continue to be major causes of morbidity and mortality worldwide, killing together around 5 million people each year. Mycolic acids, the hallmark of mycobacteria, are high-molecular weight alpha-alkyl, beta-hydroxy fatty acids. Biochemical and genetic experimental data have shown that the product of the M. tuberculosis inhA structural gene (InhA) is the primary target of isoniazid mode of action, the most prescribed anti-tubercular agent. InhA was identified as an NADH-dependent enoyl-ACP(CoA) reductase specific for long-chain enoyl thioesters and is a member of the Type II fatty acid biosynthesis system, which elongates acyl fatty acid precursors of mycolic acids. M. tuberculosis and P. falciparum enoyl reductases are targets for the development of anti-tubercular and antimalarial agents. Here we present a brief description of the mechanism of action of, and resistance to, isoniazid. In addition, data on inhibition of mycobacterial and plasmodial enoyl reductases by triclosan are presented. We also describe recent efforts to develop inhibitors of M. tuberculosis and P. falciparum enoyl reductase enzyme activity. PMID- 17348834 TI - Purine nucleoside phosphorylase: a potential target for the development of drugs to treat T-cell- and apicomplexan parasite-mediated diseases. AB - Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and thus drugs that inhibit human PNP activity have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Besides, the purine salvage pathway is the only possible way for apicomplexan parasites to obtain the building blocks for RNA and DNA synthesis, which makes PNP from these parasites an attractive target for drug development against diseases such as malaria. Hence, a number of research groups have made efforts to elucidate the mechanism of action of PNP based on structural and kinetic studies. It is conceivable that the mechanism may be different for PNPs from diverse sources, and influenced by the oligomeric state of the enzyme in solution. Furthermore, distinct transition state structures can make possible the rational design of specific inhibitors for human and apicomplexan enzymes. Here, we review the current status of these research efforts to elucidate the mechanism of PNP-catalyzed chemical reaction, focusing on the mammalian and Plamodium falciparum enzymes, targets for drug development against, respectively, T-Cell- and Apicomplexan parasites-mediated diseases. PMID- 17348835 TI - Mycobacterial shikimate pathway enzymes as targets for drug design. AB - The aetiological agent of tuberculosis (TB), Mycobacterium tuberculosis, is responsible for millions of deaths annually. The increasing prevalence of the disease, the emergence of multidrug-resistant strains, and the devastating effect of human immunodeficiency virus co-infection have led to an urgent need for the development of new and more efficient antimycobacterial drugs. Since the shikimate pathway is present and essential in algae, higher plants, bacteria, and fungi, but absent from mammals, the gene products of the common pathway might represent attractive targets for the development of new antimycobacterial agents. In this review we describe studies on shikimate pathway enzymes, including enzyme kinetics and structural data. We have focused on mycobacterial shikimate pathway enzymes as potential targets for the development of new anti-TB agents. PMID- 17348836 TI - Chorismate synthase: an attractive target for drug development against orphan diseases. AB - The increase in incidence of infectious diseases worldwide, particularly in developing countries, is worrying. Each year, 14 million people are killed by infectious diseases, mainly HIV/AIDS, respiratory infections, malaria and tuberculosis.. Despite the great burden in the poor countries, drug discovery to treat tropical diseases has come to a standstill. There is no interest by the pharmaceutical industry in drug development against the major diseases of the poor countries, since the financial return cannot be guaranteed. This has created an urgent need for new therapeutics to neglected diseases. A possible approach has been the exploitation of the inhibition of unique targets, vital to the pathogen such as the shikimate pathway enzymes, which are present in bacteria, fungi and apicomplexan parasites but are absent in mammals. The chorismate synthase (CS) catalyses the seventh step in this pathway, the conversion of 5 enolpyruvylshikimate-3-phosphate to chorismate. The strict requirement for a reduced flavin mononucleotide and the anti 1,4 elimination are both unusual aspects which make CS reaction unique among flavin-dependent enzymes, representing an important target for the chemotherapeutic agents development. In this review we present the main biochemical features of CS from bacterial and fungal sources and their difference from the apicomplexan CS. The CS mechanisms proposed are discussed and compared with structural data. The CS structures of some organisms are compared and their distinct features analyzed. Some known CS inhibitors are presented and the main characteristics are discussed. The structural and kinetics data reviewed here can be useful for the design of inhibitors. PMID- 17348837 TI - The inhibition of 5-enolpyruvylshikimate-3-phosphate synthase as a model for development of novel antimicrobials. AB - EPSP synthase (EPSPS) is an essential enzyme in the shikimate pathway, transferring the enolpyruvyl group of phosphoenolpyruvate to shikimate-3 phosphate to form 5-enolpyruvyl-3-shikimate phosphate and inorganic phosphate. This enzyme is composed of two domains, which are formed by three copies of betaalphabetaalphabetabeta-folding units; in between there are two crossover chain segments hinging the nearly topologically symmetrical domains together and allowing conformational changes necessary for substrate conversion. The reaction is ordered with shikimate-3-phosphate binding first, followed by phosphoenolpyruvate, and then by the subsequent release of phosphate and EPSP. N [phosphomethyl]glycine (glyphosate) is the commercial inhibitor of this enzyme. Apparently, the binding of shikimate-3-phosphate is necessary for glyphosate binding, since it induces the closure of the two domains to form the active site in the interdomain cleft. However, it is somehow controversial whether binding of shikimate-3-phosphate alone is enough to induce the complete conversion to the closed state. The phosphoenolpyruvate binding site seems to be located mainly on the C-terminal domain, while the binding site of shikimate-3-phosphate is located primarily in the N-terminal domain residues. However, recent results demonstrate that the active site of the enzyme undergoes structural changes upon inhibitor binding on a scale that cannot be predicted by conventional computational methods. Studies of molecular docking based on the interaction of known EPSPS structures with (R)- phosphonate TI analogue reveal that more experimental data on the structure and dynamics of various EPSPS-ligand complexes are needed to more effectively apply structure-based drug design of this enzyme in the future. PMID- 17348838 TI - Shikimate kinase: a potential target for development of novel antitubercular agents. AB - Tuberculosis (TB) remains the leading cause of mortality due to a bacterial pathogen, Mycobacterium tuberculosis. However, no new classes of drugs for TB have been developed in the past 30 years. Therefore there is an urgent need to develop faster acting and effective new antitubercular agents, preferably belonging to new structural classes, to better combat TB, including MDR-TB, to shorten the duration of current treatment to improve patient compliance, and to provide effective treatment of latent tuberculosis infection. The enzymes in the shikimate pathway are potential targets for development of a new generation of antitubercular drugs. The shikimate pathway has been shown by disruption of aroK gene to be essential for the Mycobacterium tuberculosis. The shikimate kinase (SK) catalyses the phosphorylation of the 3-hydroxyl group of shikimic acid (shikimate) using ATP as a co-substrate. SK belongs to family of nucleoside monophosphate (NMP) kinases. The enzyme is an alpha/beta protein consisting of a central sheet of five parallel beta-strands flanked by alpha-helices. The shikimate kinases are composed of three domains: Core domain, Lid domain and Shikimate-binding domain. The Lid and Shikimate-binding domains are responsible for large conformational changes during catalysis. More recently, the precise interactions between SK and substrate have been elucidated, showing the binding of shikimate with three charged residues conserved among the SK sequences. The elucidation of interactions between MtSK and their substrates is crucial for the development of a new generation of drugs against tuberculosis through rational drug design. PMID- 17348839 TI - Potentiality of small interfering RNAs (siRNA) as recent therapeutic targets for gene-silencing. AB - In recent years, RNA interference (RNAi) is one of the most important discoveries. RNAi is an evolutionarily conserved mechanism for silencing gene expression by targeted degradation of mRNA. Short double-stranded RNAs, known as small interfering RNAs (siRNA), are incorporated into an RNA-induced silencing complex that directs degradation of RNA containing a homologous sequence. siRNA has been shown to work in mammalian cells, and can inhibit viral infection and control tumor cell growth in vitro. Recently, it has been shown that intravenous injection of siRNA or of plasmids expressing sequences processed to siRNA can protect mice from autoimmune and viral hepatitis. In this review, we have discussed about the discovery of RNAi and siRNA, mechanism of siRNA mediated gene silencing, mediated gene silencing in mammalian cells, vectored delivery of siRNA, pharmaceutical potentiality of siRNA from mice to human. We have also discussed about promise and hurdles of siRNA or RNAi that could provide an exciting new therapeutic modality for treating infection, cancer, neurodegenerative disease, antiviral diseases (like viral hepatitis and HIV-1), huntington's disease, hematological disease, pain research and therapy, sarcoma research and therapy and many other illness in details. It will be a tool for stem cell biology research and now, it is a therapeutic target for gene silencing. PMID- 17348840 TI - Identifying and attaining LDL-C goals: mission accomplished? Next target: new therapeutic options to raise HDL-C levels. AB - Currently, low density lipoprotein cholesterol (LDL-C) levels are the main, if not the only, lipid target in the effort to reduce cardiovascular disease (CVD) morbidity and mortality. Several primary and secondary CVD prevention trials with statins shaped current guidelines and provided detailed targets across a range of CVD risk categories. These targets can be attained using effective statins or combination therapy. However, the net benefit in CVD risk reduction may be improved if we address other lipid risk factors. High density lipoprotein cholesterol (HDL-C) emerges from epidemiological studies as the most promising target. This review links the increase in HDL-C levels with clinical benefit from "old" (e.g. sustained release niacin) and new treatment options. Synthetically produced recombined apolipoprotein A-I Milano administered intravenously seems to have a marked effect in reducing the atheroma burden. The anti-cholesterol ester transfer protein (CETP) vaccine (CETi-1) produces auto-antibodies against CETP thus increasing the cholesterol ester content in HDL particles. CETP inhibitors (e.g. JTT-705 and torcetrapib) seem to be the most promising regimen to increase HDL-C levels. Torcetrapib (already in phase IIIa studies) can substantially increase HDL-C levels (up to 106%), alone or in combination with atorvastatin. HDL-C strategies, in combination with effective statins, are a new drug target aimed at a further reduction in CVD morbidity and mortality compared with statin monotherapy. PMID- 17348842 TI - NF-kappa B signaling and carcinogenesis. AB - NF-kappaB is an inducible transcription factor that is controlled by the signal activation cascades. NF-kappaB controls a number of genes involved in immuno inflammatory responses, cell cycle progression, inhibition of apoptosis and cell adhesion, thus promoting carcinogenesis and cancer progression. Interestingly, some proteins encoded by oncogenes and oncogenic viruses have been shown to be involved in NF-kappaB activation pathway. In fact, NF-kappaB is constitutively activated in some cancer and leukemia cells. These findings have substantiated the old concept of the link between chronic inflammation and carcinogenesis. In this review, we have attempted to overview the possible involvement of NF-kappaB in cancer and discuss the feasibility of anti-cancer strategy with NF-kappaB and its signaling cascade as novel molecular targets. PMID- 17348843 TI - Targeting different signaling pathways with antisense oligonucleotides combination for cancer therapy. AB - The evidence that cancer development is a complex and multistep process, characterized by alterations of genes involved in the regulation of proliferation, apoptosis and angiogenesis, has led to development of new therapeutic strategies based on the use of agents able to selectively inhibit key molecules of these pathways. In particular, antisense oligonucleotides (ASOs) have proved their efficacy as targeted therapy in preclinical studies, have been well tolerated and able to modulate target protein expression in clinical studies. Although these agents have shown considerable promise for antitumoral therapy, treatment with ASOs used as single agent does not seem particularly promising because of the multigenic alterations of tumors. Based on these considerations, approaches based on the combination of ASOs targeting oncogenes involved in different molecular pathways have been investigated. Moreover, the role of this novel strategy when integrated with conventional drugs or signaling inhibitors, has been assessed. This review addresses some advances in the ASOs combination and reports the potential application of this strategy for the treatment of human cancer. PMID- 17348844 TI - Proteasome as an emerging therapeutic target in cancer. AB - The 26S proteasome is a multicatalytic intracellular protease expressed in eukaryotic cells. It is responsible for selective degradation of intracellular proteins that are responsible for cell proliferation, growth, regulation of apoptosis and transcription of genes involved in execution of key cellular functions. Thus proteasome inhibition is a potential treatment option for cancer and diseases due to aberrant inflammation condition. Treatment with proteasome inhibitors results in stabilization and accumulation proteasome substrates, a phenomenon that may result in confounding signals in cells, cell cycle arrest and activation of apoptotic programs. The inhibition of the transcriptional factor nuclear factor kappaB (NF-kappaB) activation was found as one of crucial mechanisms in induction of apoptosis, overcoming resistance mechanisms and inhibition of immune response and inflammation mechanisms. Bortezomib (PS-341) and PS-519 are the first proteasome inhibitors that have entered clinical trials. In multiple myeloma, both the FDA (United States Food and Drug Administration) and EMEA (European Medicine Evaluation Agency) granted an approval for the use of bortezomib (Velcade) for the treatment of relapsed multiple myeloma. At present, several phase II and phase III trials in hematological malignancies and solid tumors are ongoing. PS-519 that focuses on inflammation, reperfusion injury and ischemia is currently under evaluation for the indication of acute stroke. PMID- 17348845 TI - Novel therapeutic approaches based on the targeting of microenvironment-derived survival pathways in human cancer: experimental models and translational issues. AB - It is a current idea that carcinogenesis as well as tumor progression are dynamic processes, which involve inherited as well as somatic mutations and include a continuing adaptation to different microenvironmental conditions. There is, in fact, rising evidence that tumor cells are under a persistent stress and that autocrine as well as microenvironment-derived survival factors play a substantial role for the final outcome of the tumor development as well as for response to the anti-tumor therapy. We will review current achievements on the molecular biology of the microenvironment-derived survival signaling and therapeutical approaches, which are presently under clinical development. By the use of plasma cell disorders as an outstanding clinical model, we will discuss the development of novel in vivo preclinical models which recapitulate the human bone marrow milieu. Finally, we will discuss several topics which appear to be relevant for a successful clinical translation of preclinical research in this specific field. PMID- 17348846 TI - Targeted therapy of breast cancer. AB - Breast cancer is the most frequent tumor of women. The development of effective adjuvant therapy based on postoperative administration of short-term chemotherapy (4-6 months) or long-term hormone therapy (5 years) or both, significantly improved survival of patients. However, therapy of adjuvant/metastatic disease is still palliative with a very low probability to induce complete remission and definitive cure of disease. The relevant efforts of basic research to identify the key and selective molecular alterations, which sustain breast cancer growth and progression allowed the possibility to develop specific molecular target treatments. Trastuzumab, a humanized monoclonal antibody to HER-2, is the first molecular targeting agent approved for therapy of metastatic breast cancer, capable to significantly improve clinical outcome in combination with cytotoxic therapy. Recent preliminary data from randomized, prospective, clinical trials suggest that trastuzumab decreases the risk of early recurrence by 50% in patients with HER-2-positive disease. Other novel targeted treatments are in clinical evaluation, including antiangiogenic compounds (Bevacizumab, sunitinib, vatalanib, and others) and bi-functional drugs such as lapatinib (anti Her-2 and EGFR agent) showing promising activity. This review provides an updated overview of the status of development of targeted therapy in breast cancer, as well as the challenges related to the rational use of molecular targeting agents. PMID- 17348847 TI - Current concepts for the combined treatment modality of ionizing radiation with anticancer agents. AB - In current applied radiobiology, there exists a tremendous effort in basic and translational research to identify novel treatment modalities combining ionizing radiation with anticancer agents. This is mainly due to the highly improved molecular understanding of intrinsic radioresistance and the profiling of cellular stress responses to irradiation during recent years. Ionizing radiation not only damages DNA but also affects multiple cellular components that induce a multi-layered stress response. The treatment responses can be restricted to the individual cell level but might also be part of an intercellular stress communication network. Both DNA damage-induced signaling (which results in cell cycle arrest and induction of the DNA-repair machinery) and also ionizing radiation-induced signal transduction cascades, which are generated at cellular sites distant from and independent of DNA-damage, represent interesting targets for anticancer treatment modalities to sensitize for ionizing radiation. Due to the lack of molecular knowledge classic radiobiology assembled the cellular and tissue responses into four groups (4 R's of radiotherapy) which describe biological factors influencing the treatment response to fractionated radiotherapy. These classic 4 R's are Repair, Reassortment, Repopulation and Reoxygenation. With the tremendous progress in molecular oncology we now begin to understand theses factors on the molecular level. At the same time this classification may guide modern molecular radiobiologists to identify novel pharmaceuticals and antisignaling agents which can modulate the treatment response to irradiation. In this review we describe current approaches to sensitize tumor cells with novel anticancer agents along the lines of these 4 R's. PMID- 17348848 TI - Towards the development of tumor necrosis factor (TNF) sensitizers: making TNF work against cancer. AB - Although TNF antitumor activity has been demonstrated in many preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Moreover, due to systemic toxicity, TNF can only be administered through sophisticated locoregional drug-delivery systems in patients with some types of organ-confined solid tumors; as a corollary, the impossibility to administer TNF through the systemic route does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. A challenge many researchers are tackling is to dissect the cascade of molecular events underlying tumor sensitivity to TNF so to fully explore the anticancer potential of this molecule. The rationale for the development of strategies aimed at sensitizing malignant cells to TNF is to exploit tumor-specific molecular derangements to modulate TNF biological activities and ultimately maximize its tumor-selective cytotoxicity. This would not only enhance the anticancer activity of current TNF-based locoregional regimens, but would also open the avenue to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field. In this review we first summarize the molecular biology of TNF and its cancer-related properties; then, the available findings regarding some among the most promising and best characterized TNF sensitizers are overviewed. PMID- 17348849 TI - Antileishmanial and antimalarial chalcones: synthesis, efficacy and cytotoxicity of pyridinyl and naphthalenyl analogs. AB - The antileishmanial and antimalarial activity of methoxy-substituted chalcones (1,3-diphenyl-2-propen-1-ones) is well established. The few analogs prepared to date where the 3-phenyl group is replaced by either a pyridine or naphthalene suggest these modifications are potency enhancing. To explore this hypothesis, sixteen 3-naphthalenyl-1-phenyl-2-prop-1-enones and ten 1-phenyl-3-pyridinyl-2 prop-1-enones were synthesized and their in vitro efficacies against Leishmania donovani and Plasmodium falciparum determined. One inhibitor with submicromolar efficacy against L. donovani was identified (IC50 = 0.95 microM), along with three other potent compounds (IC50 < 5 microM), all of which were 3-pyridin-2-yl derivatives. No inhibitors with submicromolar efficacy against P. falciparum were identified, though several potent compounds were found (IC50 < 5 microM). The cytotoxicity of the five most active L. donovani inhibitors was assessed. At best the IC50 against a primary kidney cell line was around two-fold higher than against L. donovani. Being more active than pentamidine, the 1-phenyl-3-pyridin-2 yl-2-propen-1-ones have potential for further development against leishmaniasis; however it will be essential in such a program to address not only efficacy but also their potential for toxicity. PMID- 17348850 TI - Evaluation of Polygonum bistorta for anticancer potential using selected cancer cell lines. AB - The chloroform and hexane fractions and their sub-fractions of Polygonum bistorta (Polygonaceae) were evaluated for their cytotoxic activity against P338 (Murine lymphocytic leukaemia), HepG2 (Hepatocellular carcinoma), J82 (Bladder transitional carcinoma), HL60 (Human leukaemia), MCF7 (Human breast cancer) and LL2 (Lewis lung carcinoma) cancer cell lines in culture. Both the chloroform and hexane fractions and a few of their sub-fractions showed moderate to very good activity against P388, HL60 and LL2 cancer cell lines. Both active and non-active fractions were further investigated for their chemical constituents. A total of nine compounds, viz. 24(E)-ethylidenecycloartanone (1), 24(E) ethylidenecycloartan-3alpha-ol (2), cycloartane-3,24-dione (3), 24 methylenecycloartanone (4), friedelin (5), 3beta-friedelinol (6), beta-sitosterol (7), gamma-sitosterol (8) and beta-sitosterone (9) were isolated. One of the pure compounds, 24(E)-ethylidenecycloartanone 1, which was obtained in sufficient quantity, was tested for its cytotoxicity against P388, LL2, HL60 and WEHI164 (Murine fibrosarcoma) cancer cell lines but was found to have no activity even at a concentration of 100 microg/mL. PMID- 17348851 TI - 2-Amino/azido/hydrazino-5-alkoxy-5H-[1]benzopyrano[4,3-d]pyrimidines: synthesis and pharmacological evaluation. AB - New series of 5-alkoxy-benzopyranopyrimidine derivatives were developed from the chemical modulation of the substituent in position 2 of the scaffold, with the aim to produce analgesic/antiphlogistic agents more potent than analogues previously reported. The 2-hydrazino derivatives exhibited a good analgesic activity in writhing test; the analgesic doses of the compounds did not affect mice spontaneous locomotor activity thus any confounding sedative effect could be excluded. These derivatives revealed an aspirin-like profile with a strong inhibition of AA-induced platelet aggregation, probably due to a strong, non selective, inhibition of cyclooxygenases. In spite of the inhibition of COX activity displayed in vitro, the compounds did not cause gastric damage in rats after acute oral administration. A different pharmacological profile was observed for the 2-azido derivatives, particularly in vivo. PMID- 17348852 TI - Flexible estrogen receptor modulators: synthesis, biochemistry and molecular modeling studies for 3-benzyl-4,6-diarylhex-3-ene and 3,4,6-triarylhex-3-ene derivatives. AB - Selective estrogen receptor modulators (SERMs) such as tamoxifen and toremifene are clinically useful drugs in the endocrine treatment of estrogen receptor positive breast cancer while raloxifene is an effective intervention for osteoporosis. In an ongoing SERM discovery programme we now report the synthesis of a series of 3-benzyl-4,6-diarylhex-3-enes and 3,4,6-triarylhex-3-enes containing an extended flexible core structure. In these novel structures, the ethylene group acts as a flexible spacing group linking the aryl Ring A or Ring B with the core alkene group. In the benzyl-4,6-diarylhex-3-ene series an additional methylene group is inserted as a spacing group between the aryl ring C and the ethylene core group. These products demonstrated antiproliferative activity against the MCF-7 human breast cancer cell line. The alkene compounds were also shown to have binding affinity for the estrogen receptor alpha (IC50 values for the most active compounds in the range 0.110-0.293 microM) together with selectivity for ER alpha/beta. The compounds demonstrated antiestrogenic activity in Ishikawa cells with low estrogenic stimulation. The structure activity relationships for the active ligands were further explored in a computational study where docked structures of the active compounds were compared with the X-ray crystal structures for the complexes of ER alpha with 4 hydroxytamoxifen and ER beta with raloxifene. The alignment of the aromatic rings B and C of the compounds within the ligand binding domain could then be correlated with their observed ER alpha/beta selectivity. PMID- 17348853 TI - Cellular pharmacology, antineoplastic activity and low in vivo toxicity of a carboxylato-bridged platinum(II) complex bis(acetato)diammine-bis-micro-acetato diplatinum (II) dihydrate. AB - The dinuclear platinum complex bis(acetato)diammine-bis-micro-acetato diplatinum (II) dihydrate has been previously shown to exert profound cytotoxicity in diverse tumor cell lines, while being far less detrimental than the clinically applied platinum drugs against some susceptible to platinum toxicity non malignant cellular populations. In the present study we report the investigation of the cellular accumulation kinetics and apoptosis induction of the dinuclear complex in K-562, its potent in vivo antineoplastic activity against L1210 leukemia and Lewis lung carcinoma tumor models and its lower nephrotoxicity, myelosuppressive potential and clastogenicity in vivo relative to cisplatin. PMID- 17348854 TI - A quantitative structure-activity relationship study on some novel series of hydroxamic acid analogs acting as matrix metalloproteinase inhibitors. AB - A quantitative structure-activity relationship study has been made on some pyranyl hydroxamic acid analogs acting as matrix metalloproteinase (MMP) inhibitors. The inhibition potencies of two different series of compounds against two MMP enzymes (MMP-1 and MMP-13) have been analyzed and found to be well correlated with hydrophobic and some indicator parameters of the substituents. In both the cases, hydrophobic parameter of substituents has been found to be a dominant factor. The results of this study led to discuss the selectivity of the compounds for MMP-13 over MMP-1. PMID- 17348855 TI - Synthesis of phenyl-substituted amides with antioxidant and anti-inflammatory activity as novel lipoxygenase inhibitors. AB - Lipoxygenases (LO) have been implicated in several inflammatory diseases such as asthma, immune disorders, and cancers. Lipoxygenases play an essential role in the biosynthesis of the leukotrienes. Leukotrienes have been implicated as mediators in the pathophysiology of inflammatory diseases, host defense reactions and they were found to play important role in the propagation of the diseases states, exacerbating the local events and ultimately leading to tissue damage. As a consequence of these broad biological implications, there is a great interest in synthesising new compounds with this activity. The synthesis of new amides of aryl acetic acid is described. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Since lipophilicity is a significant physicochemical property determining distribution, bioavailability, metabolic activity and elimination, their lipophilicity is experimentally determined from RPTLC method. Several parameters were theoretically calculated and were used for a QSAR study. The compounds are tested in vitro on: a) soybean lipoxygenase inhibition, b) interaction with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical, c) the HO* mediated oxidation of DMSO, d) inhibition of lipid peroxidation, e) scavenging of superoxide anion radicals f) interaction with glutathione and g) in vivo for the inhibition of carrageenin induced rat paw edema. The compounds present significant antioxidant activities, medium anti inflammatory activity and potent inhibition of soybean lipoxygenase as a result of their physicochemical features. PMID- 17348856 TI - Pharmacophore modeling in drug discovery and development: an overview. AB - Pharmacophore mapping is one of the major elements of drug design in the absence of structural data of the target receptor. The tool initially applied to discovery of lead molecules now extends to lead optimization. Pharmacophores can be used as queries for retrieving potential leads from structural databases (lead discovery), for designing molecules with specific desired attributes (lead optimization), and for assessing similarity and diversity of molecules using pharmacophore fingerprints. It can also be used to align molecules based on the 3D arrangement of chemical features or to develop predictive 3D QSAR models. This review begins with a brief historical overview of the pharmacophore evolution followed by a coverage of the developments in methodologies for pharmacophore identification over the period from inception of the pharmacophore concept to recent developments of the more sophisticated tools such as Catalyst, GASP, and DISCO. In addition, we present some very recent successes of the widely used pharmacophore generation methods in drug discovery. PMID- 17348857 TI - Control of HIV through the inhibition of HIV-1 integrase: a medicinal chemistry perspective. AB - This article reviews the current status of classes of HIV-1 integrase enzyme inhibitors. These classes include peptide-based inhibitors, natural products, polyhydroxylated aromatics, diketo acids, naphthyridines, and sulfonated compounds including sulfonic acids. Discussions of structure activity relationships are presented and include the current overview of the structure based model, suitable for the further design and development. To date, the advances in the medicinal chemistry of HIV-1 integrase inhibitors have relied mostly on ligand-based designs leading to most displaying similar binding interactions within the active site or at the dimer interface. This paves the way for single enzyme mutations rendering entire compound classes inactive and thus, the requirement for second and third generation inhibitors with novel modes of binding is apparent. To facilitate future structure-based drug design efforts, a model of the biologically relevant structure of the HIV-1 integrase enzyme, a dimer of dimers has also been discussed. PMID- 17348858 TI - Requirement of Apaf-1 for mitochondrial events and the cleavage or activation of all procaspases during genotoxic stress-induced apoptosis. AB - Sequential activation of caspases is critical for the execution of apoptosis. Recent evidence suggests caspase 2 is a significant upstream caspase capable of initiating mitochondrial events, such as the release of cytochrome c. In particular, in vitro studies using recombinant proteins have shown that cleaved caspase 2 can induce mitochondrial outer membrane permeabilization directly or by cleaving the BH3-only protein BID (BH3 interacting domain death agonist). However, whether interchain cleavage or activation of procaspase 2 occurs prior to Apaf-1-mediated procaspase 9 activation under more natural conditions remains unresolved. In the present study, we show that Apaf-1-deficient Jurkat T lymphocytes and mouse embryonic fibroblasts were highly resistant to DNA-damage induced apoptosis and failed to cleave or activate any apoptotic procaspase, including caspase 2. Significantly, drug-induced cytochrome c release and loss of mitochondrial membrane potential were inhibited in cells lacking Apaf-1. By comparison, procaspase proteolysis and apoptosis were only delayed slightly in Apaf-1-deficient Jurkat cells upon treatment with anti-Fas antibody. Our data support a model in which Apaf-1 is necessary for the cleavage or activation of all procaspases and the promotion of mitochondrial apoptotic events induced by genotoxic drugs. PMID- 17348859 TI - Molecular mechanisms involved in the regulation of cytokine production by muramyl dipeptide. AB - MDP (muramyl dipeptide), a component of peptidoglycan, interacts with NOD2 (nucleotide-binding oligomerization domain 2) stimulating the NOD2-RIP2 (receptor interacting protein 2) complex to activate signalling pathways important for antibacterial defence. Here we demonstrate that the protein kinase activity of RIP2 has two functions, namely to limit the strength of downstream signalling and to stabilize the active enzyme. Thus pharmacological inhibition of RIP2 kinase with either SB 203580 [a p38 MAPK (mitogen-activated protein kinase) inhibitor] or the Src family kinase inhibitor PP2 induces a rapid and drastic decrease in the level of the RIP2 protein, which may explain why these RIP2 inhibitors block MDP-stimulated downstream signalling and the production of IL-1beta (interleukin 1beta) and TNFalpha (tumour necrosis factor-alpha). We also show that RIP2 induces the activation of the protein kinase TAK1 (transforming-growth-factor beta-activated kinase-1), that a dominant-negative mutant of TAK1 inhibits RIP2 induced activation of JNK (c-Jun N-terminal kinase) and p38alpha MAPK, and that signalling downstream of NOD2 or RIP2 is reduced by the TAK1 inhibitor (5Z)-7 oxozeaenol or in TAK1-deficient cells. We also show that MDP activates ERK1 (extracellular-signal-regulated kinase 1)/ERK2 and p38alpha MAPK in human peripheral-blood mononuclear cells and that the activity of both MAPKs and TAK1 are required for MDP-induced signalling and production of IL-1beta and TNFalpha in these cells. Taken together, our results indicate that the MDP-NOD2/RIP2 and LPS (lipopolysaccharide)-TLR4 (Toll-like receptor 4) signalling pathways converge at the level of TAK1 and that many subsequent events that lead to the production of pro-inflammatory cytokines are common to both pathways. PMID- 17348860 TI - Widespread neuronal expression of branched-chain aminotransferase in the CNS: implications for leucine/glutamate metabolism and for signaling by amino acids. AB - Transamination of the branched-chain amino acids produces glutamate and branched chain alpha-ketoacids. The reaction is catalyzed by branched-chain aminotransferase (BCAT), of which there are cytosolic and mitochondrial isoforms (BCATc and BCATm). BCATc accounts for 70% of brain BCAT activity, and contributes at least 30% of the nitrogen required for glutamate synthesis. In previous work, we showed that BCATc is present in the processes of glutamatergic neurons and in cell bodies of GABAergic neurons in hippocampus and cerebellum. Here we show that this metabolic enzyme is expressed throughout the brain and spinal cord, with distinct differences in regional and intracellular patterns of expression. In the cerebral cortex, BCATc is present in GABAergic interneurons and in pyramidal cell axons and proximal dendrites. Axonal labeling for BCATc continues into the corpus callosum and internal capsule. BCATc is expressed by GABAergic neurons in the basal ganglia and by glutamatergic neurons in the hypothalamus, midbrain, brainstem, and dorsal root ganglia. BCATc is also expressed in hypothalamic peptidergic neurons, brainstem serotoninergic neurons, and spinal cord motor neurons. The results indicate that BCATc accumulates in neuronal cell bodies in some regions, while elsewhere it is exported to axons and nerve terminals. The enzyme is in a position to influence pools of glutamate in a variety of neuronal types. BCATc may also provide neurons with sensitivity to nutrient-derived BCAAs, which may be important in regions that control feeding behavior, such as the arcuate nucleus of the hypothalamus, where neurons express high levels of BCATc. PMID- 17348861 TI - IGF-I-induced oligodendrocyte progenitor proliferation requires PI3K/Akt, MEK/ERK, and Src-like tyrosine kinases. AB - Insulin-like growth factor-I (IGF-I) is required for the growth of oligodendrocytes, although the underlying mechanisms are not fully understood. Our aim was to investigate the role of phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase kinase (MEK1), and Src family tyrosine kinases in IGF-I-stimulated proliferation of oligodendrocyte progenitors. IGF-I treatment increased the proliferation of cultured oligodendrocyte progenitors as determined by measuring incorporation of [(3)H]-thymidine and bromodeoxy-uridine (BrdU). IGF I stimulated a transient phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK1) and extracellular signal-regulated kinases (ERK1/2) (targets of MEK1), as well as a rapid and sustained activation of Akt (a target of PI3K). Furthermore, inhibitors of PI3K (LY294002 and Wortmannin), MEK1 (PD98059 and U0126), and Src family tyrosine kinases (PP2) decreased IGF-I-induced proliferation, and blocked ERK1/2 activation. LY294002, Wortmannin and PP2 also blocked Akt activation. To further determine whether Akt is required for IGF-I stimulated oligodendrocyte progenitor proliferation, cultures were infected with adenovirus vectors expressing dominant-negative mutants of Akt or treated with pharmacological inhibitors of Akt. All treatments reduced IGF-I-induced oligodendrocyte progenitor proliferation. Our data indicate that stimulation of oligodendrocyte progenitor proliferation by IGF-I requires Src-like tyrosine kinases as well as the PI3K/Akt and MEK1/ERK signaling pathways. PMID- 17348862 TI - Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis. AB - Calnuc, a Golgi calcium binding protein, plays a key role in the constitution of calcium storage. Abnormal calcium homeostasis has been linked to Alzheimer's disease (AD). Excessive production and/or accumulation of beta-amyloid (Abeta) peptides that are proteolytically derived from the beta-amyloid precursor protein (APP) have been linked to the pathogenesis of AD. APP has also been indicated to play multiple physiological functions. In this study, we demonstrate that calnuc interacts with APP through direct binding to the carboxyl-terminal region of APP, possibly in a calcium-sensitive manner. Immunofluorescence study revealed that the two proteins co-localize in the Golgi in both cultured cells and mouse brains. Over-expression of calnuc in neuroblastoma cells significantly reduces the level of endogenous APP. Conversely, down-regulation of calnuc by siRNA increases cellular levels of APP. Additionally, we show that over-expression of calnuc down-regulates the APP mRNA level and inhibits APP biosynthesis, which in turn results in a parallel reduction of APP proteolytic metabolites, sAPP, CTFs and Abeta. Furthermore, we found that the level of calnuc was significantly decreased in the brain of AD patients as compared with that of age-matched non-AD controls. Our results suggest a novel function of calnuc in modulating the levels of APP and its proteolytic metabolites, which may further affect the patho/physiological functions of APP including AD pathogenesis. PMID- 17348863 TI - Enhanced proliferation of astrocytes from beta(2)-adrenergic receptor knockout mice is influenced by the IGF system. AB - In the present study, we investigated the IGF system in neonatal astrocytes derived from mice with a targeted disruption of the beta-2 adrenergic receptor (beta(2)AR). beta(2)AR knockout astrocytes demonstrated higher proliferation rates and increased expression of the astrogliotic marker GFAP, as compared with wild-type cells. beta(2)AR deletion also regulated molecules of the IGF system. Although IGF-1 levels remained unaltered, IGF-2 and type 1 IGF receptor expression was increased in beta(2)AR knockout cells. Furthermore, conditioned medium from knockout astrocytes contained lower levels of IGF binding protein-2 and -4. Our data suggest a deficit of beta(2)AR on astrocytes, as previously reported in multiple sclerosis, may have implications on proliferative status of astrocytes, a feature that might be attributed to regulation of IGF mitogenic actions. PMID- 17348864 TI - Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice. AB - Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) function to remodel the pericellular environment. Their activation and regulation are associated with synaptic physiology and pathology. Here, we investigated whether MMP-2 and MMP-9 are involved in the rewarding effects of and sensitization to methamphetamine (METH) in animals, in which the remodelling of neural circuits may play a crucial role. Repeated METH treatment induced behavioural sensitization, which was accompanied by an increase in MMP-2 and MMP-9 activity in the brain. In MMP-2- and MMP-9-deficient mice [MMP-2-(-/-) and MMP-9-(-/-)], METH-induced behavioural sensitization and conditioned place preference, a measure of the rewarding effect, as well as METH-increased dopamine release in the nucleus accumbens (NAc) were attenuated compared with those in wild-type mice. In contrast, infusion of purified human MMP-2 into the NAc significantly potentiated the METH-increased dopamine release. The [(3)H]dopamine uptake into striatal synaptosomes was reduced in wild-type mice after repeated METH treatment, but METH-induced changes in [(3)H]dopamine uptake were significantly attenuated in MMP-2-(-/-) and MMP-9-( /-) mice. These results suggest that both MMP-2 and MMP-9 play a crucial role in METH-induced behavioural sensitization and reward by regulating METH-induced dopamine release and uptake in the NAc. PMID- 17348865 TI - Modulation of electrically evoked serotonin release in cultured rat raphe neurons. AB - Electrically evoked release of serotonin (5-HT) and its modulation via 5-HT autoreceptors and alpha(2)-heteroreceptors was studied in primary cell cultures prepared from the embryonic (ED 15) rat mesencephalic brain region comprising the raphe nuclei. Cultures were grown for up to 3 weeks on circular glass coverslips. They developed a dense network of non-neuronal and neuronal cells, some of which were positive for tryptophan hydroxylase. To measure 5-HT release, the cultures were pre-incubated with [(3)H]5-HT (in the presence of the selective noradrenaline reuptake inhibitor oxaprotiline [1 micromol/L]), superfused with modified Krebs-Henseleit medium containing 6-nitroqipazine [1 micromol/L] and electrically stimulated using two conditions. Condition A: 360 pulses, 3 Hz, 0.5 ms, 90 mA, or condition B: 4 pulses 100 Hz, 0.5 ms, 90 mA (a condition which diminishes interactions with endogenously released transmitters during ongoing stimulation). After only 1 week in culture, the electrically evoked overflow of [(3)H] was Ca(2+) dependent and tetrodotoxin sensitive, suggesting an action potential-induced exocytotic release of 5-HT. Using stimulation condition A in cultures grown for 2 weeks, both basal and evoked 5-HT release were strongly enhanced by methiotepine (1 micromol/L) but unaffected by the 5-HT(1B) autoreceptor agonist CP-93, 129 (1 micromol/L) and the alpha(2)-adrenoceptor agonist UK-14, 304 (1 micromol/L). Conversely, using stimulation condition B, not only CP-93, 129 (IC(50) 8.1 +/- 1.4 nmol/L) and UK-14, 304 (IC(50) 14.9 +/- 1.6 nmol/L) had inhibitory effects on cells grown for 2 weeks, but also the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin. In conclusion, we describe for the first time electrically evoked release of 5-HT from primary cultures of fetal raphe cells and its modulation via 5-HT(1B) and 5-HT(1A) auto- and alpha(2) heteroreceptors. Such cultured raphe cells may represent a suitable model to study expression and development of presynaptic receptors on serotonergic neurons in-vitro. PMID- 17348866 TI - Hypoxia-like transcriptional activation in TMT-induced degeneration: microarray expression analysis on PC12 cells. AB - To more clearly elucidate the complete network of molecular mechanisms induced by trimethyltin (TMT) toxicity, we used a homogeneous cell culture model represented by PC12 cells treated with 1 and 5 micromol/L TMT for 24 h. The gene expression profile was performed by microarray analysis, enabling us to identify 189 genes that were significantly modulated in treated cells, compared with controls. The main effects of TMT on gene expression seem to be related to the activation of metabolic processes (glycolysis and lipogenesis) along with cell death pathways, membrane remodeling and intracellular biomolecules trafficking. These alterations are triggered by the neurotoxicant earlier than a strong decrease in cell viability, which occurs at higher TMT concentrations or at later time points. Some aspects of the transcriptional modulation observed in this study resemble the gene activation known to occur during cell response to hypoxia. Other cell toxicants have also been reported to exert similar effects on gene expression. Therefore, our data help to delineate general basic adaptive mechanisms possibly shared by cells responding to different death-inducing noxae, such as TMT. PMID- 17348867 TI - The value of Good Manufacturing Practice to a Blood Service in managing the delivery of quality. AB - The delivery of 'quality' in transfusion medicine is addressed by considering how safe and efficacious blood, blood components, reagents, and services can be provided through the application of an effective quality assurance management system. The creation of such a system in the UK is reviewed through the development of the UK Guide to Good Pharmaceutical Manufacturing Practice from 1971 to the present. It provides simple practical guidance and standards. The UK experience shows how quality assurance has evolved, it is not offered as a model to be followed. The UK approach merged with that of the European Union from the early 1990s. The use of such a quality management system to support the application of licensing and accreditation standards relevant to the work of a modern Blood Service is considered, as are processes to learn about the effective and efficacious use of blood and blood components. PMID- 17348868 TI - Antibody therapy (IVIG): evaluation of the use of genomics and proteomics for the study of immunomodulation therapeutics. AB - BACKGROUND AND OBJECTIVES: Intravenous immunoglobulin (IVIG) is used for an increasingly diverse number of therapeutic applications as an immunomodulation drug. Although it has demonstrated therapeutic effectiveness, the mechanism of action of IVIG in these disorders is poorly understood; this lack of understanding complicates rational clinical application and reimbursement for 'off-label' use. MATERIALS AND METHODS: Selected literature on the clinical use of IVIG as an immunomodulation drug is reviewed. We present a brief description of DNA microarray and protein microarray technology and the application of such technologies to the study of immune system cells. The several studies on the application of DNA microarray technology to study gene expression in response to IVIG are presented. RESULTS: There is increasing data on the use of DNA microarray and protein microarray technology to study gene expression in immune system cells including T cells, B cells, macrophages, and leucocytes. There is less information on the effect of IVIG on gene expression in immune system cells. However, there is sufficient information available to suggest that this is a practical approach with the caveat that such work will require careful experimental design and clear definition of the normal population. CONCLUSIONS: DNA and protein microarray assays can be used to (i) provide rational indications for the clinical use of IVIG, (ii) provide for specific analysis of raw material and end product IVIG in screening for content related to immunomodulation, and (iii) accelerate the development of next generation products which would be more focused and/or targeted therapeutics. PMID- 17348869 TI - Normal levels of ADAMTS13 and factor H are present in the pharmaceutically licensed plasma for transfusion (Octaplas) and in the universally applicable plasma (Uniplas) in development. AB - BACKGROUND AND OBJECTIVES: The pathomechanism of thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS) is associated with a severe deficiency of ADAMTS13 and factor H. The aim of this study was to quantify the levels of ADAMTS13 and factor H in the pharmaceutically licensed plasma for transfusion, Octaplas, and the universally applicable plasma, Uniplas (development product, working title). Furthermore, Octaplas batches of blood groups A, B, O, AB, and plasmas derived from different sources were compared. MATERIALS AND METHODS: Twenty-four Octaplas and three Uniplas batches were selected for the study. ADAMTS13 activities were measured by fluorescence resonance energy transfer assay, ADAMTS13 antigen levels were quantified using enzyme-linked immunosorbent assay test kit, while factor H antigen levels were detected using radial immunodiffusion (RID) methods. In addition, von Willebrand factor (vWF) multimeric analyses were performed. RESULTS: Both Octaplas, produced from US and European plasma of different blood groups, and Uniplas contain ADAMTS13 antigen and activity levels as well as factor H concentrations at normal levels without significant differences. In addition, Octaplas and Uniplas show a vWF multimeric pattern comparable to normal plasma. CONCLUSION: The study revealed that Octaplas and Uniplas contain normal levels of ADAMTS13 at low batch to-batch variations. Therefore, both products can substitute the missing or neutralized protease activity in TTP patients and thereby limit vWF-dependent (platelet-related) thrombosis. In addition, both plasma products contain factor H at a physiological level, and, thus can be used efficiently in the treatment of aHUS patients, which have been shown to benefit from plasma administration. PMID- 17348870 TI - Transfusion-related inhibition of cytokines (TRICK). Experimental transfer of neutralizing autoantibodies to interleukin-6 by plasma transfusions. AB - BACKGROUND: For some unknown reason humans may 'spontaneously' produce high amounts of neutralizing autoantibodies to a number of growth factors and cytokines. Reaching a certain high level the antibodies render the person cytokine deficient, mostly without overt clinical manifestations. The autoantibodies in question are detectable in normal immunoglobulin preparations and correspondingly in normal human plasma for transfusion. High affinity neutralizing autoantibodies to interleukin-6 (aAb-IL-6) are present in high titres in 0.1% of plasma from blood donors. Using aAb-IL-6 as a model we here report the first study addressing transfer of cytokine autoantibodies with blood components. MATERIALS AND METHODS: We transferred high amounts of aAb-IL-6 to two patients suffering from end-stage disease of multiple myeloma. This was done by serial transfusions with normal human plasma highly positive for aAb-IL-6. We assessed recovery and kinetics of the transferred aAb-IL-6 and exposed how the recipients' plasma IL-6 bound to aAb-IL-6. RESULTS: Free IL-6 was detectable in plasma of the recipients before transfusion. After the first transfusion IL-6 became immune complexed to aAb-IL-6 the molar plasma concentrations of which exceeded total IL-6 at least 500 times. CONCLUSION: The observations signify that high amounts of neutralizing autoantibodies to cytokines (in this context aAb-IL 6) are occasionally transferred by transfusion. Although neither beneficial nor obvious detrimental effects of the plasmas were observed in this study our measurements evidently uncover a hitherto unknown form of transfusion-related immune modulation: transfusion-related inhibition of cytokines (TRICK). Depending on the cytokine autoantibody in question, the phenomenon might affect immune responses to infection and recovery after stem cell transplantation. PMID- 17348871 TI - White-blood-cell-containing allogeneic blood transfusion and postoperative infection or mortality: an updated meta-analysis. AB - BACKGROUND: Additional randomized controlled trials (RCTs) comparing recipients of non-white-blood-cell-(WBC)-reduced and WBC-reduced allogeneic red blood cells (RBCs) have been reported since the undertaking of previous meta-analyses of the association of allogeneic blood transfusion (ABT) with postoperative infection and/or mortality. Because no further RCTs are underway, a final meta-analysis of all available RCTs was conducted. METHODS: RCTs reporting on the association of ABT with postoperative infection and/or short-term (up to 3-month post transfusion), all-cause mortality were retrieved. Twelve RCTs reporting on infection and 11 RCTs reporting on mortality were eligible for meta-analysis. Summary odds ratios (ORs) of infection or mortality in recipients of WBC containing ABT vs. WBC-reduced ABT were calculated across the studies. RESULTS: An association of ABT with postoperative infection was demonstrated across RCTs transfusing RBCs WBC-reduced after storage [summary OR = 2.25; 95% confidence interval (CI), 1.12-4.25] but not before storage (summary OR = 1.06; 95% CI, 0.91 1.24). An association of ABT with mortality was demonstrated across RCTs conducted in cardiac surgery (summary OR = 1.72, 95% CI, 1.05-2.81) and across RCTs transfusing buffy-coat-reduced RBCs vs. RBCs WBC-reduced before storage (summary OR = 1.60; 95% CI, 1.14-2.24), but not across RCTs transfusing non-buffy coat-reduced RBCs vs. RBCs WBC-reduced before storage (summary OR = 1.01; 95% CI, 0.73-1.40). CONCLUSIONS: An association between ABT and postoperative infection or short-term mortality is not detected across all clinical settings and transfused RBC products. An association between ABT and mortality is detected in cardiac surgery, but the other associations found in subgroup analyses contradict current theories about mechanism(s) of the ABT effect. PMID- 17348872 TI - Seven hundred and fifty-nine (759) chances to learn: a 3-year pilot project to analyse transfusion-related near-miss events in the Republic of Ireland. AB - BACKGROUND: The National Haemovigilance Office has collected and analysed reports on errors associated with transfusion since 2000. A 3-year pilot research project in near-miss event reporting commenced in November 2002. MATERIALS AND METHODS: Near-miss reports from 10 hospital sites were analysed between May 2003 and May 2005. The Medical Event Reporting System for Transfusion Medicine was used to collect and analyse the data. Root cause analysis was used to identify causes of error. RESULTS: A total of 759 near-miss events were reported. Near misses are occurring 18 times more frequently than adverse events causing harm. Sample collection was found to be the highest risk step in the work process and was the first site of error in 468 (62%) events. Of these, 13 (3%) involved samples taken from the wrong patient. Medical staff were frequently involved in error. The general wards and emergency department were identified as high-risk clinical areas, in addition, 78 (10%) events occurred within the transfusion laboratory. Three specific human and two system failures were shown to have been associated with the errors identified in this study. CONCLUSIONS: This study confirms that near-miss events occur far more frequently than adverse events causing harm. Collecting near-miss data is an effective means of highlighting human and system failures associated with transfusion that may otherwise go unnoticed. These data can be used to identify areas where resources need to be targeted in order to prevent future harm to patients, improving the overall safety of transfusion. PMID- 17348873 TI - Molecular and family analyses revealed two novel RHD alleles in a survey of a Chinese RhD-negative population. AB - BACKGROUND AND OBJECTIVES: RHD alleles are considered variable in the Chinese RhD negative persons. The purpose of the present work was to elucidate the molecular bases of two novel RHD alleles identified in a survey of a Chinese RhD-negative population. MATERIALS AND METHODS: A total of 163 RhD-negative blood samples were investigated. The sequences of RHD exons were examined by RHD exon specific multiplex polymerase chain reaction (PCR) and PCR with sequence-specific primers (PCR-SSP). Characterizations of RHD intron 2 and Rhesus box were performed by PCR PstI digestion. The DNA and cDNA sequences of the novel alleles were determined by PCR and reverse transcriptase-PCR (RT-PCR) sequencing analysis. A family study was performed to investigate the segregation of a novel RHD allele. RESULTS: One hundred and twenty-nine samples (79.1%) had no RHD gene. Twenty-seven samples (16.6%) carried RHD-CE-D hybrid alleles. The remainder seven samples (4.3%) appeared to have an intact RHD gene. Three of them were sequenced for RHD gene and two novel alleles, RHD 325del and RHD intron 2 1A, were identified. The deletion of a nucleotide A at position 325 in the allele RHD 325del resulted in a stop codon at amino acid position 118. The RHD intron 2 1A allele was generated from a splice mutation and its transcript sequence had no exon 2. Family study indicated that the RHD 325del allele was inherited with a Ce haplotype. CONCLUSION: This study provides the molecular bases of RHD alleles RHD 325del and RHD intron 2 1A. The existences of RHD 711del, RH (D1 CE2-9 D10), and RH (D1 CE2 9 D10) alleles in the Chinese population were confirmed. A PCR-SSP-based assay for rapid detection of RHD 325del and RHD intron 2 1A alleles was established and it could be used to predict the RHD genotype in the Chinese RhD-negative subjects. PMID- 17348874 TI - Leucocyte antibodies in blood donors and a look back on recipients of their blood components. AB - BACKGROUND AND AIM: The role of leucocyte antibodies in donors is poorly understood in pathogenesis of transfusion-related acute lung injury (TRALI). We examined antibodies in donors and traced recipients transfused with their blood components. MATERIAL AND METHODS: Antibodies were examined in 1043 donors by five methods, look back performed in 26 recipients. RESULTS: Anti-human leucocyte antigen detected by enzyme-linked immunosorbent assay in 9.8% women but none in men. Specificities identified using FlowPRA, antibodies detected after several months. TRALI reported in one recipient from immunized donor. In 11 of 26 recipients without TRALI, cognate antigens were identified. CONCLUSION: Detection of antibodies in donors cannot predict TRALI, even in recipients with cognate antigen(s). PMID- 17348875 TI - International Society of Blood Transfusion Committee on Terminology for Red Cell Surface Antigens: Cape Town report. PMID- 17348876 TI - International collaborative study proposal for the characterization of occult hepatitis B virus infection identified by nucleic acid or anti-HBc screening. AB - The International Society of Blood Transfusion (ISBT) transfusion-transmitted infections (TTI) working party is proposing to undertake an international collaborative study aimed at understanding occult hepatitis B infection by molecular and immunological characterization, determining infectivity by transfusion and clinical relevance of this newly identified condition. This article provides information to the transfusion community and aims to recruit potential collaborators for the study. Further information can be obtained from the author or the ISBT TTI working group website (http://www.isbt-web.org). PMID- 17348877 TI - Measures to prevent TRALI. PMID- 17348879 TI - Osseointegration of Osseotite and machined-surfaced titanium implants in membrane covered critical-sized defects: a histologic and histometric study in dogs. AB - The texture of an implant's surface can influence the rate and extent of bone fixation as expressed by the amount of linear bone-to-implant contact (BIC). The purpose of this study was to compare the bone density and linear BIC between Osseotite and machined-surface implants placed in bony defects without graft material and covered by a membrane. Thirty 2 mm diameter, 10 mm length custom implants were prepared for this study having a 'split surface,' with one side having the acid-etched surface and the opposite side having a machined surface. Defects were created in the iliac wing of three adult mongrel dogs where a 6-mm diameter drill was used to generate a 5-mm-deep defect. The implants were inserted into the center of the defect with 5 mm secured into the bone leaving 5 mm free in the defect with a 2 mm gap between the implant and surrounding bone. Expanded polytetrafluroethelyene membranes were placed over the defect sites stabilized with Biotack pins. The healing times were 2, 3, and 5 months. Histologic and histometric analysis showed significantly lower BIC in the defect region as compared with the portion of implant placed into native bone for both implant surfaces in all groups. There was no difference in BIC values at 2- and 5 month periods between the two surfaces in the regenerated area, while BIC values for Osseotite surfaces were significantly higher than the machined surfaces at 3 months' healing time. Changes in bone density, observed between the three groups, affected correspondingly the BIC values in both implant surfaces, the effect being more pronounced in the Osseotite surface. PMID- 17348880 TI - Comparison of naturally occurring and ligature-induced peri-implantitis bone defects in humans and dogs. AB - OBJECTIVES: The aim of the present study was to evaluate and compare naturally occuring and ligature-induced peri-implantitis bone defects in humans and dogs. MATERIAL AND METHODS: Twenty-four partially and fully edentulous patients undergoing peri-implant bone augmentation procedures due to advanced peri-implant infections were included in this study (n=40 implants). Furthermore, peri implantitis was induced by ligature placement and plaque accumulation in five beagle dogs for three months following implant insertion (n=15 implants). The ligatures were removed when about 30% of the initial bone was lost. During open flap surgery, configuration and defect characteristics of the peri-implant bone loss were recorded in both humans and dogs. RESULTS: Open flap surgery generally revealed two different classes of peri-implant bone defects. While Class I defects featured well-defined intrabony components, Class II defects were characterized by consistent horizontal bone loss. The allocation of intrabony components of Class I defects regarding the implant body allowed a subdivision of five different configurations (Classes Ia-e). In particular, human defects were most frequently Class Ie (55.3%), followed by Ib (15.8%), Ic (13.3%), Id (10.2%), and Ia (5.4%). Similarly, bone defects in dogs were also most frequently Class Ie (86.6%), while merely two out of 15 defects were Classes Ia and Ic (6.7%, respectively). CONCLUSIONS: Within the limits of the present study, it might be concluded that configurations and sizes of ligature-induced peri-implantitis bone defects in dogs seemed to resemble naturally occurring lesions in humans. PMID- 17348881 TI - Healing of surgically created circumferential gap around non-submerged-type implants in dogs: a histomorphometric study. AB - OBJECTIVES: This study was conducted to evaluate the healing of surgically created circumferential gaps around non-submerged-type implants according to varying size and healing periods in dogs. MATERIAL AND METHODS: In four mongrel dogs, all mandible premolars were extracted and after an 8-week healing period, non-submerged-type implants were placed. Circumferential coronal defects around the implants were performed surgically with a customized tapered step drill. Groups were divided according to the width of the coronal gaps: 1, 1.5, or 2 mm. First the right side of the mandible was prepared, and after 8 weeks, the left side was prepared. The dogs were sacrificed following an 8-week healing period. Specimens were analyzed histologically and histomorphometrically. RESULTS: As the size of the coronal gap increased, the unfilled area tended to be greater. In terms of bone-to-implant contact and bone density, both the 1 and 1.5 mm groups showed a larger percentage of coronal defect than the apical side, while the 2 mm group showed contrary results in the 8-week groups. The general histologic features in the 16-week groups were similar to the findings of 8-week groups but were more matured, with a higher percentage of lamellar bone. A certain amount of bone filling and osseointegration was observed in the defects of all the groups. CONCLUSION: It can be concluded that the remaining defect, small enough to be clinically neglected, irrespective of gap size within 2 mm, does not need any kind of regenerating procedures. PMID- 17348882 TI - Therapy of peri-implantitis with resective surgery. A 3-year clinical trial on rough screw-shaped oral implants. Part II: radiographic outcome. AB - OBJECTIVES: This clinical study on therapy of peri-implantitis aimed to compare the marginal bone loss of implants treated with different surgical approaches: implantoplasty and peri-implant resective surgery only. MATERIAL AND METHODS: Over a period of 6 years, 10 patients (20 implants) were treated with implantoplasty (test group) and 9 had resective surgery (control group). A computerized analysis of radiographs was performed to calculate marginal bone loss (MBL) values mesial and distal to the implants. The measurement system was set by means of known implant sizes. Data on MBL were collected at the time of peri-implantitis diagnosis, 1, 2 and 3 years after surgery. RESULTS: There was no difference between the mean MBL values three years after implantoplasty in the test group: 0 and 0.01 mm of MBL mesial and distal to the implant were found (P>0.05). Conversely, the mean MBL values recorded in the control group were statistically different: 1.44 and 1.54 mm of MBL mesial and distal to the implant were found (P<0.05) 3 years after resective surgery. Moreover, the variation of peri-implant marginal bone after peri-implantitis surgical treatment was significantly lower in the test group than in the control group (P<0.05). CONCLUSIONS: The results of this radiographic research suggested that implantoplasty was an effective treatment of peri-implant infections and peri implantitis progression. PMID- 17348883 TI - Immediate implant placement with transmucosal healing in areas of aesthetic priority. A multicentre randomized-controlled clinical trial I. Surgical outcomes. AB - OBJECTIVES: To compare the clinical outcomes of standard, cylindrical, screw shaped to novel tapered, transmucosal (Straumann Dental implants immediately placed into extraction sockets. MATERIAL AND METHODS: In this randomized controlled clinical trial, outcomes were evaluated over a 3-year observation period. This report deals with the need for bone augmentation, healing events, implant stability and patient-centred outcomes up to 3 months only. Nine centres contributed a total of 208 immediate implant placements. All surgical and post surgical procedures and the evaluation parameters were discussed with representatives of all centres during a calibration meeting. Following careful luxation of the designated tooth, allocation of the devices was randomly performed by a central study registrar. The allocated SLA titanium implant was installed at the bottom or in the palatal wall of the extraction socket until primary stability was reached. If the extraction socket was >or=1 mm larger than the implant, guided bone regeneration was performed simultaneously (Bio Oss and BioGide. The flaps were then sutured. During non-submerged transmucosal healing, everything was done to prevent infection. At surgery, the need for augmentation and the degree of wound closure was verified. Implant stability was assessed clinically and by means of resonance frequency analysis (RFA) at surgery and after 3 months. Wound healing was evaluated after 1, 2, 6 and 12 weeks post operatively. RESULTS: The demographic data did not show any differences between the patients receiving either standard cylindrical or tapered implants. All implants yielded uneventful healing with 15% wound dehiscences after 1 week. After 2 weeks, 93%, after 6 weeks 96%, and after 12 weeks 100% of the flaps were closed. Ninety percent of both implant designs required bone augmentation. Immediately after implantation, RFA values were 55.8 and 56.7 and at 3 months 59.4 and 61.1 for cylindrical and tapered implants, respectively. Patient-centred outcomes did not differ between the two implant designs. However, a clear preference of the surgeon's perception for the appropriateness of the novel tapered implant was evident. CONCLUSIONS: This RCT has demonstrated that tapered or standard cylindrical implants yielded clinically equivalent short-term outcomes after immediate implant placement into the extraction socket. PMID- 17348884 TI - Patient-centred outcomes comparing transmucosal implant placement with an open approach in the maxilla: a prospective, non-randomized pilot study. AB - It was the aim of the study to assess differences in patient morbidity between transmucosal implant placement and implant installation after elevation of mucoperiosteal flaps. In five of the patients, implants were placed in the maxilla transmucosally using a CAD/CAM surgical template [test group (TG)]. In the remaining five patients, the implants were installed after the elevation of mucoperiosteal flaps [control group (CG)]. Directly after surgery, at days 1 and 7 after surgery the patients rated pain and discomfort on a visual analogue scale (0=minimal pain and discomfort, 100=maximal pain and discomfort). Optical three dimensional images were assessed preoperatively and at days 1 and 7 after surgery to determine the visible soft tissue swelling of the upper lip and cheeks. Directly postoperatively, the mean pairwise difference between both groups in view of pain and discomfort ratings (control minus test) was 45.6 (SD, 20.7). At days 1 and 7, the mean differences were 51.6 (SD, 21.8) and 19 (SD, 8), respectively. The overall test of the area under curve (AUC) against the null hypothesis 'AUC of pairwise differences of pain score over study time equals null' yielded a significant difference (P=0.01). The mean pairwise difference between both groups in view of soft tissue volume increase was 6.1 (SD, 2) cm(3) at day 1 after surgery and 4.6 (SD, 1.2) cm(3) at day 7. The overall test of the AUC against the null hypothesis 'AUC of pairwise differences of oedema measurements over study time equals null' yielded a significant difference (P=0.002). Within the limitations of this pilot study, it could be shown that transmucosal implant placement reduces patient morbidity significantly compared with an open approach. PMID- 17348885 TI - Clinical evaluation of demineralized bone allograft in a hyaluronic acid carrier for sinus lift augmentation in humans: a computed tomography and histomorphometric study. AB - OBJECTIVES: Natural and synthetic graft materials are used routinely in sinus floor augmentations to help support implants in atrophic maxillary ridges. This clinical study was based on the hypothesis that the clinical effectiveness of demineralized freeze-dried bone allograft/demineralized bone matrix (DFDBA/DBM) in sinus lifts varies when used in combination bone graft substitute materials. To test this hypothesis, DFDBA was used together with one of three materials: in saline plus anorganic bone (DFDBA: Bio-Oss; in hyaluronic acid (DFDBA: HY, 32 : 68, w/w; DBX alone; DBX plus Bio-Oss; and DBX plus tricalcium phosphate granules (beta-TCP). MATERIAL AND METHODS: Thirty-two sinus lift procedures, eight per group, were performed on 26 patients. Before surgery and at 8 months post-surgery when implants were placed, ridge heights were visualized by computed tomography (CT) and measured by morphometric analysis. Cores of bone were removed by trephine at the sites of implant placement; these biopsies from the graft sites were used for histomorphometric analysis. RESULTS: All 32 sinus lift elevations were successful when measured by CT, increasing from an average 2.84+/-0.2 mm before treatment to 15.2+/-0.6 mm after treatment. The percent of each biopsy that was occupied by new bone and incorporated bone graft materials varied with each treatment: DFDBA+Bio-Oss, DBX+Bio-Oss, or DBX alone was higher than that for DBX+beta-TCP by approximately 10%. When comparing only newly formed bone, DBX+beta-TCP treatment resulted in 50% less bone than the other three preparations. All grafted sites received implants as per the treatment plan for each patient. CONCLUSIONS: This study confirmed the hypothesis that new bone formation is dependent on the DFDBA formulation used and demonstrated that DBX, alone or in combination with other materials, can be used successfully for sinus floor elevation. PMID- 17348886 TI - Associations between peri-implant crevicular fluid volume, concentrations of crevicular inflammatory mediators, and composite IL-1A -889 and IL-1B +3954 genotype. A cross-sectional study on implant recall patients with and without clinical signs of peri-implantitis. AB - OBJECTIVES: To assess possible relationships between peri-implant crevicular fluid (PICF) volumes, biochemical markers of the peri-implant immune response, and periodontitis-associated genotype. MATERIAL AND METHODS: PICF samples from 29 implant maintenance patients, 24 wearing overdentures, five having single crowns and bridgework (11 patients with peri-implantitis and 18 individuals with healthy peri-implant conditions), were analyzed for per site and per crevicular-fluid volume concentrations of interleukin-1beta, plasminogen activator inhibitor type 2, and prostaglandin E2 by ELISA. Associations between the three substance concentrations and to crevicular fluid flow rate were analyzed by linear regression analysis. The possible differentiating influence of the composite interleukin-1A and -1B genotype on the patients' peri-implant health and biochemical inflammatory status was checked formally with t-test statistics and the Wilcoxon' test. One implant per patient was chosen for analysis. RESULTS: In patients with healthy peri-implant conditions, genotype-positive individuals showed elevated crevicular fluid flow rates and at the same time reduced mediator concentrations. In patients with an implant affected from peri-implantitis, no statistically significant influence of the periodontitis-associated genotype around the fixture can be stated. There was no statistical difference between per site and per crevicular-fluid-volume concentration analyses. All three mediator concentrations were positively related to each other, while there was a strong negative correlation between crevicular fluid volume and plasminogen activator inhibitor 2 or prostaglandin E2. CONCLUSIONS: The Interleukin-1 polymorphism investigated exerted only little influence on the peri-implant crevicular immune response, and this influence appeared to be of limited impact in sites with established peri-implantitis lesions. PMID- 17348887 TI - Bone reconstruction following implantation of rhBMP-2 and guided bone regeneration in canine alveolar ridge defects. AB - BACKGROUND: Alveolar ridge aberrations commonly require bone augmentation procedures for optimal placement of endosseous dental implants. The objective of this study was to evaluate local bone formation following implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier with or without provisions for guided bone regeneration (GBR) as potential treatment modalities for alveolar augmentation. METHODS: Surgically induced, large, mandibular alveolar ridge saddle-type defects (2 defects/jaw quadrant) in seven young adult Hound dogs were assigned to receive rhBMP-2/ACS, rhBMP-2/ACS combined with GBR (rhBMP-2/GBR), GBR, and surgery controls. The animals were euthanized at 12 weeks post-surgery when block sections of the defect sites were collected for histologic analysis. RESULTS: Clinical complications included swelling for sites receiving rhBMP-2 and wound failure with exposure of the barrier device for sites receiving GBR (4/6) or rhBMP-2/GBR (3/7). The radiographic evaluation showed substantial bone fill for sites receiving rhBMP-2/ACS, rhBMP-2/GBR, and GBR. In particular, sites receiving rhBMP-2/GBR presented with seroma-like radiolucencies. The surgery control exhibited moderate bone fill. To evaluate the biologic potential of the specific protocols, sites exhibiting wound failure were excluded from the histometric analysis. Sites receiving rhBMP-2/ACS or rhBMP-2/GBR exhibited bone fill averaging 101%. Bone fill averaged 92% and 60%, respectively, for sites receiving GBR and surgery controls. Bone density ranged from 50% to 57% for sites receiving rhBMP-2/ACS, GBR, or surgery controls. Bone density for sites receiving rhBMP 2/GBR averaged 34% largely due to seroma formation encompassing 13% to 97% of the sites. CONCLUSION: rhBMP-2/ACS appears to be an effective alternative to GBR in the reconstruction of advanced alveolar ridge defects. Combining rhBMP-2/ACS with GBR appears to be of limited value due to the potential for wound failure or persistent seromas. PMID- 17348888 TI - Tactile sensibility of single-tooth implants and natural teeth. AB - AIM: The purpose of this randomized split-mouth clinical trial was to determine the active tactile sensibility between single-tooth implants and opposing natural teeth and to compare it with the tactile sensibility of pairs of natural teeth on the contralateral side in the same mouth (intraindividual comparison). MATERIAL AND METHODS: The hypothesis was that the active tactile sensibilities of the implant side and control side are equivalent. Sixty two subjects (n=36 from Bonn, n=26 from Bern) with single-tooth implants (22 anterior and 40 posterior dental implants) were asked to bite on narrow copper foil strips varying in thickness (5 200 microm) and to decide whether or not they were able to identify a foreign body between their teeth. Active tactile sensibility was defined as the 50% threshold of correct answers estimated by means of the Weibull distribution. RESULTS: The results obtained for the interocclusal perception sensibility differed between subjects far more than they differed between natural teeth and implants in the same individual [implant/natural tooth: 16.7+/-11.3 microm (0.6 53.1 microm); natural tooth/natural tooth: 14.3+/-10.6 microm (0.5-68.2 microm)]. The intraindividual differences only amounted to a mean value of 2.4+/-9.4 microm (-15.1 to 27.5 microm). The result of our statistical calculations showed that the active tactile sensibility of single-tooth implants, both in the anterior and posterior region of the mouth, in combination with a natural opposing tooth is similar to that of pairs of opposing natural teeth (double t-test, equivalence margin: +/-8 microm, P<0.001, power >80%). Hence, the implants could be integrated in the stomatognathic control circuit. PMID- 17348889 TI - Soft and hard tissue assessment of immediate implant placement: a case series. AB - OBJECTIVES: The aim of this prospective study was to evaluate clinically and radiographically the success and esthetic result of immediate implant placement at the time of extraction. MATERIAL AND METHODS: Twelve patients with 14 titanium screw-shaped implants (13-16 mm length and 4.3 or 5 mm diameters) were placed in the extraction sockets. Defects after implant placement were recorded, and then filled up with deproteinized bovine bone mineral, bioabsorbable collagen membrane, and absorbable pins. The defect was again re-evaluated at second-stage surgery. Clinical and radiographic parameters of the peri-implant conditions were assessed at the moment of prosthesis placement and at 1-year follow-up. RESULTS: The cumulative implant survival and success rate was 100% after a 1-year observation period. Analysis of the esthetic result showed that the mean pink esthetic score (PES) was 11.1 (SD 1.35) at 1-year follow-up. At 1 year, 64.3% papillae had a score of 2 and the remaining 35.7% score 3 according to the Jemt (1997) papillary index. Optimal value of width of the keratinized mucosa was recorded in 13 (92.9%) implant cases in both periods of follow-up. At 1-year follow-up, the linear distance between implant-shoulder to the bone peaks remains stable with a mean of 2.62+/-0.2 mm at the mesial and 2.9+/-0.58 mm at the distal aspect. CONCLUSION: Careful evaluation of potential extraction sites before immediate implant installation promotes optimal implant esthetics. PMID- 17348890 TI - Early effect of platelet-rich plasma on bone healing in combination with an osteoconductive material in rat cranial defects. AB - OBJECTIVE: The early effect of platelet-rich plasma (PRP) on bone regeneration in combination with dense biphasic hydroxyl apatite (HA)/beta-tricalcium phosphate (TCP) particles (ratio 60%/40%) was evaluated in rat cranial defects with a diameter of 6.2 mm. We hypothesize that PRP exerts its beneficial effect on bone regeneration within the first and second week after application in a bone defect combined with an osteoconductive material. MATERIALS AND METHODS: Forty-five rats were used in the study, in which always one cranial defect was created. The defects were filled with HA/beta-TCP particles and HA/beta-TCP particles combined with PRP gel. Some defects were also left unfilled as control. One and two weeks after surgery specimens were retrieved for light microscopy [hematoxylin-eosin, trichrome staining (Masson modification Goldner) and basic fuchsin-methylene blue] and micro-CT analysis to evaluate bone formation and neovascularization. One-way analysis of variance was performed on the raw data obtained from micro-CT analyses. RESULTS: The histological evaluation showed no effect of PRP on bone formation and neovascularization for both implantation times. In the first week, the defect closure was evaluated subjectively to be between 10% and 50% in all samples, whereas no difference among the groups appeared to occur. After 2 weeks, complete bridging of the original bone defect was observed for most of the empty defects, as well as for the defects that contained HA/beta-TCP particles. The trichrome staining revealed no difference in the number of blood vessels between the PRP and non-PRP groups for both implantation times. The osteoconductive nature of dense HA/beta-TCP particles was confirmed, as the bone formation was guided by their outer surfaces and resulted in a larger amount of newly formed bone in comparison with the empty defects. The quantitative micro-CT analysis demonstrated a statistically significant difference in new bone formation between the empty defects and defects filled with particles after 1 week of implantation, but there was no difference between the non-PRP and PRP groups. In at the second week, no difference in bone formation among all groups was observed, whereas even the non-filled control defects were almost completely closed. CONCLUSIONS: A 6.2 mm cranial defect is not a critical-sized defect in rats. Rat PRP had no effect on the early stages of bone healing in addition to an osteoconductive material. Dense HA/beta-TCP particles showed a beneficial effect on bone formation already after 1 and 2 weeks of implantation in non-critical-sized cranial defects in rats. PMID- 17348891 TI - Platelet-rich plasma activity on maxillary sinus floor augmentation by autologous bone. AB - OBJECTIVES: This work aims to evaluate the regenerative potential of platelet rich plasma (PRP) on an implant site of peculiar clinical impact, such as sinus augmentation. MATERIAL AND METHODS: Sixteen consenting patients (11 females and five males), with symmetrical maxillary sinus atrophy, underwent bilateral sinus floor augmentation, using autologous (iliac crest) bone on one side and PRP plus autologous bone contralaterally. Implants were inserted 4, 5, 6 and 7 months after surgery in the patients randomly split into four groups. Orthopantomographies, computed tomography with transverse image digital reconstructions and densitometries were used to monitor the treatment progress. A core biopsy was performed at the site of implant. RESULTS: Clinical performance across both sites showed no statistical significance (P=0.414). Densitometric values were higher at PRP sites (mean Hounsfield units approximately +57%), even if densitometry converged in the two sites 8 months after surgery. Histology documents enhanced bone activities in sites treated with PRP, 4 months after surgery. Reduced bone activity was observed in both sites 5, 6 and 7 months after surgery. Bone amount, higher in sites treated with PRP (mean trabecular bone volume approximately +37%), decreased in both sites over time. CONCLUSIONS: Our results seem to indicate a certain regenerative potential of PRP when used with autologous bone. The effect of this enhancement of bone regeneration appeared to be restricted to shorter treatment times. A progressive extinguishment of the PRP effect is recorded after an interval longer than 6-7 months. PMID- 17348892 TI - Success rate of mini- and micro-implants used for orthodontic anchorage: a prospective clinical study. AB - OBJECTIVES: Whereas micro-implants have become a useful alternative as orthodontic anchorage elements in orthodontics, less is known about the clinical effectiveness of micro-implants. The aim of this prospective clinical study was to evaluate the success rate of micro-implants used for orthodontic anchorage. MATERIAL AND METHODS: A total of 133 mini-implants (79 Abso Anchor, 54 Dual Top implants) placed in 49 patients to support orthodontic tooth movements were examined in the study. The majority of the implants were placed in the maxilla (82), followed by the vestibular (42) and lingual (nine) aspect of the mandible. RESULTS: An overall cumulative survival rate of 86.8% (102/133) was found by Kaplan-Meier analysis. The failure rate between Dual Top implants (13%) and Abso Anchor implants (30.4%) differed significantly (P=0.0196; log-rank test). The cumulative failure rate of implants was found to be significantly higher when implants were placed in the lingual aspect of the mandible compared with the other localizations (P=0.0011; log-rank test). Clinical evaluation revealed successful dental movements when implants remained stable during the orthodontic therapy. CONCLUSIONS: The present results confirm the effectiveness of orthodontic micro-implants used as anchorage elements. PMID- 17348893 TI - Pesticides and the intoxication of wild animals. AB - Pesticides are widely used to control agricultural pests. Unfortunately, because of their biological activity, they may have detrimental effects on nontarget species. Acute toxicity, resulting in death, is reported worldwide. Although chronic and indirect effects may be even more hazardous for animal populations on a long-term basis, they are usually evaluated as parts of research programs. The purpose of this paper was to review the wildlife-poisoning surveillance systems and their results regarding the circumstances of exposure of wild animals, the pesticides involved and the species exposed. Most data are retrieved from the British and French pesticide poisoning surveillance systems in wildlife, with some data from other European structures. PMID- 17348894 TI - Pharmacokinetics of boldenone and stanozolol and the results of quantification of anabolic and androgenic steroids in race horses and nonrace horses. AB - Anabolic steroids (ABS) boldenone (BL; 1.1 mg/kg) and stanozolol (ST; 0.55 mg/kg) were administered i.m. to horses and the plasma samples collected up to 64 days. Anabolic steroids and androgenic steroids (ANS) in plasma were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The limit of detection of all analytes was 25 pg/mL. The median absorption (t1/2 partial differential) and elimination (t1/2e) half-lives for BL were 8.5 h and 123.0 h, respectively, and the area under the plasma concentration-time curve (AUCho) was 274.8 ng.h/mL. The median t1/2e for ST was 82.1 h and the was 700.1 ng.h/mL. Peak mean (X+/-SD) plasma concentrations (Cmax) for BL and ST were 1127.8 and 4118.2 pg/mL, respectively. Quantifiable concentrations of ABS and ANS were found in 61.7% of the 988 plasma samples tested from race tracks. In 17.3% of the plasma samples two or more ABS or ANS were quantifiable. Testosterone (TES) concentrations mean (X+/-SE) in racing and nonracing intact males were 241.3+/-61.3 and 490.4+/-35.1 pg/mL, respectively. TES was not quantified in nonracing geldings and female horses, but was in racing females and geldings. Plasma concentrations of endogenous 19-nortestosterone (nandrolone; NA) from racing and nonracing males were 50.2+/-5.5 and 71.8+/-4.6 pg/mL, respectively. PMID- 17348895 TI - Pulmonary disposition of erythromycin, azithromycin, and clarithromycin in foals. AB - The objectives of the present study were to determine and compare the pulmonary disposition of azithromycin, clarithromycin, and erythromycin in foals. A single dose (10 mg/kg) of azithromycin, clarithromycin, or erythromycin was administered intragastrically to six healthy 1- to 3-month-old foals using an orthogonal design. Activity of the drugs was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells by use of a microbiologic assay. Peak drug activity in PELF was significantly higher in foals treated with clarithromycin (48.96+/-13.26 microg/mL) than in foals treated with azithromycin (10.00+/-7.46 microg/mL). Quantifiable erythromycin activity in PELF was only found in two of six foals. Peak drug activity in BAL cells was not significantly different between azithromycin (49.92+/-26.94 microg/mL) and clarithromycin (74.20+/-45.80 microg/mL) but activity for both drugs was significantly higher than that of erythromycin (1.02+/-1.11 microg/mL). Terminal half-life of azithromycin in serum (25.7+/-15.4 h), PELF (34.8+/-30.9 h), and BAL cells (54.4+/-17.5 h) was significantly longer than that of both clarithromycin and erythromycin. Peak azithromycin and clarithromycin activity was significantly higher in BAL cells, followed by PELF, and serum. In contrast, peak erythromycin activity in BAL cells was not significantly different from that of serum. PMID- 17348896 TI - Effects of physiological covariables on pharmacokinetic parameters of clomipramine in a large population of cats after a single oral administration. AB - This study was conducted to confirm an interindividual variability in pharmacokinetic parameters of clomipramine in a large population of cats and to identify potential covariables that would explain the presence of such pharmacokinetic variability after a single dose of Clomicalm. Clomipramine hydrochloride was administered orally according to a weight-dose chart from 0.32 to 0.61 mg/kg, to 76 cats and five blood samples were then taken by direct venipuncture at 1, 3, 6, 12, and 24 h. Plasma concentrations of clomipramine and desmethylclomipramine (DCMP) were measured by LC-MS/MS. The Standard Two-Stage technique was used to assess differences and detect correlations between pharmacokinetic parameter estimates and individual covariables. A large interindividual variability in all pharmacokinetic parameters (CV% 64-124) was detected. Statistically significant gender-related differences were detected in MR and Cl/F, where female cats had a higher mean MR (0.53) and faster Cl/F (0.36 L/h.kg) than males (0.36 and 0.21 L/h.kg, respectively). No correlation could be found between clomipramine AUC0-24 h or DCMP AUC0-24 h and sedation scores. Further feline studies are required to assess these findings after multiple dosing of clomipramine and DCMP to allow clinical extrapolation. PMID- 17348897 TI - Metoclopramide modifies oral cephalexin pharmacokinetics in dogs. AB - The purpose of this study was to investigate whether previous administration of metoclopramide affects cephalexin pharmacokinetics after its oral administration in dogs as well as whether these changes impair its predicted clinical efficacy. Six healthy beagle dogs were included in this study. Oral 25 mg/kg cephalexin monohydrate and intravenous 0.5 mg/kg metoclopramide HCl single doses were administered. Each dog received cephalexin or cephalexin following metoclopramide, with a 2-week washout period. Plasma concentrations of cephalexin were determined by microbiological assay. Cephalexin peak plasma concentration and area under the curve from 0 to infinity significantly increased from 18.77+/ 2.8 microg/mL and 82.65+/-10.4 microg.h/mL to 21.88+/-0.8 microg/mL and 113.10+/ 20.9 microg.h/mL, respectively, after pretreatment with metoclopramide. No differences between treatments were found for other pharmacokinetic parameters. Pharmacokinetic/pharmacodynamic indices calculated for highly susceptible staphylococci were similar for both experiences. Metoclopramide pretreatment may have increased cephalexin absorption by affecting its delivery to the intestine, and/or enhancing intestinal transporter PEPT1 function. Neither difference in the efficacy of cephalexin nor an increase in toxicity is expected as a result of this modification. Consequently, no dose adjustment is required in cephalexin treated patients pretreated with metoclopramide. PMID- 17348898 TI - Bioavailability of a silybin-phosphatidylcholine complex in dogs. AB - Liver dysfunction often is associated with an imbalance in the production and removal of free radicals derived from oxygen and nitrogen and has been managed clinically with antioxidant supplements, including silymarin extract derived from milk thistle. The potential for enhanced bioavailability of a phytosome complex containing phosphatidylcholine and silybin, the primary active flavonolignan in silymarin extract, was tested in dogs. A group of eight beagles (four males, four females) were dosed orally with a silybin-phosphatidylcholine complex (SPC) and a commercially available standardized silymarin extract containing equivalent levels of silybin. Dosing with the SPC resulted in Cmax, Tmax, and AUC0-24 h values (mean+/-SD) for total silybin of 1310+/-880 ng/mL, 2.87+/-2.23 h, and 11,200+/-6520 ng.h/mL, respectively; corresponding values for a standardized silymarin extract were 472+/-383 ng/mL, 4.75+/-2.82 h, and 3720+/-4970 ng.h/mL. A second, separate group of beagles were also dosed with the extract alone, yielding values of 449+/-402 ng/mL, 6.87+/-7.43 h, and 2520+/-2976 ng.h/mL. These data show that a phytosome complex of phosphatidylcholine and silybin markedly enhances bioavailability in dogs. PMID- 17348899 TI - Pharmacokinetics and bioavailability of spectinomycin after i.v., i.m., s.c. and oral administration in broiler chickens. AB - A pharmacokinetic and bioavailability study of spectinomycin was conducted in healthy broiler chickens following administration of a single (50 mg/kg bw) intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) dose and oral doses of 50 and 100 mg/kg bw. Following i.v. administration, the elimination half life (t1/2beta), mean residence time (MRT), volume of distribution at steady state (Vd(ss)), volume of distribution based on the terminal phase (Vd(z)) and total body clearance (ClB) were 1.46+/-1.10 h, 1.61+/-1.05 h, 0.26+/-0.009 L/kg, 0.34 (0.30-0.38) L/kg and 2.68+/-0.017 mL/min/kg respectively. After i.m. and s.c. dosing, the Cmax was 152.76+/-1.08 and 99.77+/-1.04 microg/mL, achieved at 0.25 (0.25-0.50) and 0.25 (0.25-1.00) h, the t1/2beta was 1.65+/-1.07 and 2.03+/ 1.06 h and the absolute bioavailability (F) was 136.1% and 128.8% respectively. A significant difference in Cmax (5.13+/-0.10, 14.26+/-1.12 microg/mL), t1/2beta (3.74+/-1.07, 8.93+/-1.13 h) and ClB/F (22.69+/-0.018, 10.14+/-0.018 mL/min/kg) were found between the two oral doses (50 and 100 mg/kg bw respectively), but there were no differences in the tmax [2.00 (2.00-4.00), 2.00 (2.00-2.00) h] and Vd(z)/F [6.95 (6.34-9.06), 7.98 (4.75-10.62) L/kg). The absolute bioavailability (F) of spectinomycin was 11.8% and 26.4% after oral administration of 50 and 100 mg/kg bw respectively. PMID- 17348900 TI - Pharmacokinetics of florfenicol, thiamphenicol, and chloramphenicol in turkeys. AB - The pharmacokinetics of florfenicol (FF), thiamphenicol (TP) and chloramphenicol (CP) after single intravenous (i.v.) or oral (p.o.) administration was studied in an independent cross-over study in broiler turkeys. All the fenicol antibiotics were administered at a dose of 30 mg/kg b.w. and their concentrations in plasma samples were assayed using the same validated high-performance liquid chromatography method. Pharmacokinetic parameters were calculated by a noncompartmental method. The kinetic profiles of the compounds were compared with the results of the structure-activity relationship. According to the proposed mathematical description, no differences in plasma clearance values for the studied antibiotics were observed. The mean residence time values of FF, TF, and CP after i.v. injection were 3.37+/-0.63, 2.43+/-0.29, and 2.12+/-0.21 h, respectively. The mean values of Varea for FF (1.39+/-0.31 L/kg) and TP (1.31+/ 0.19 L/kg) were similar, but significantly different from that of CP (1.04+/-0.12 L/kg). The bioavailabilities of FF, TP, and CP after oral administration were 82%, 69%, and 45%, respectively. Differences in the bioavailability values of the compared fenicol antibiotics correspond to the ratio of the apolar/polar surface areas of their particles. PMID- 17348901 TI - Intracellular killing of mastitis pathogens by penethamate hydriodide following internalization into mammary epithelial cells. AB - Penethamate hydriodide was highly effective in killing Streptococcus uberis, Streptococcus dysgalactiae subsp. dysgalactiae and Staphylococcus aureus that internalized mammary epithelial cells. At higher concentrations (32 microg/mL to 32 mg/mL), killing rates ranged from 85% to 100%. At lower concentrations (0.032 microg/mL to 3.2 microg/mL), killing rates ranged from 0 to 80%. Results of this proof-of-concept study demonstrated that: (1) penethamate hydriodide is capable of entering mammary epithelial cells and killing intracellular mastitis pathogens without affecting mammary epithelial cell viability, (2) the in vitro model used is capable of quantifying the fate of mastitis pathogens internalized into mammary epithelial cells, and (3) this in vitro model can be used to determine the effectiveness of antibiotics at killing bacteria within the cytoplasm of mammary epithelial cells. PMID- 17348902 TI - Pharmacokinetics and bioavailability of nimesulide in goats. AB - The pharmacokinetic properties and bioavailability of cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drug nimesulide were investigated in female goats following intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 4 mg/kg BW. Blood samples were collected by jugular venipuncture at predetermined times after drug administration. Plasma concentrations of nimesulide were determined by a validated high-performance liquid chromatography method. Plasma concentration-time data were subjected to compartmental analysis and pharmacokinetic parameters for nimesulide after i.v. and i.m. administration were calculated according to two- and one-compartment open models respectively. Following i.v. administration, a rapid distribution phase was followed by the slower elimination phase. The half-lives during the distribution phase (t1/2alpha) and terminal elimination phase (t1/2beta) were 0.11+/-0.10 and 7.99+/ 2.23 h respectively. The steady-state volume of distribution (Vd(ss)), total body clearance (ClB) and mean residence time (MRT) of nimesulide were 0.64+/-0.13 L/kg, 0.06+/-0.02 L/h/kg and 11.72+/-3.42 h respectively. After i.m. administration, maximum plasma concentration (Cmax) of nimesulide was 2.83+/-1.11 microg/mL attained at 3.6+/-0.89 h (tmax). Plasma drug levels were detectable up to 72 h. Following i.m. injection, the t1/2beta and MRT of nimesulide were 1.63 and 1.73 times longer, respectively, than the i.v. administration. The bioavailability of nimesulide was 68.25% after i.m. administration at 4 mg/kg BW. These pharmacokinetic data suggest that nimesulide given intramuscularly may be useful in the treatment of inflammatory disease conditions in goats. PMID- 17348903 TI - Identification of the genes encoding for putative gamma aminobutyric acid (GABA) and glutamate-gated chloride channel (GluCl) alpha receptor subunits in sea lice (Lepeophtheirus salmonis). PMID- 17348904 TI - Pharmacokinetics of metronidazole in the red-eared slider turtle (Trachemys scripta elegans) after single intracoelomic injection. PMID- 17348905 TI - Pharmacokinetics of a novel amoxicillin paste formulation in cats. PMID- 17348906 TI - Red blood cell erythropoietin, not plasma erythropoietin, concentrations correlate with changes in hematological indices in horses receiving a single dose of recombinant human erythropoietin by subcutaneous injection. PMID- 17348907 TI - Spurious urine excretion drug profile in the horse due to bedding contamination and drug recycling: the case of meclofenamic acid. PMID- 17348909 TI - Inactivation of avian influenza viruses by chemical agents and physical conditions: a review. AB - The recent outbreaks of avian influenza (AI) worldwide have highlighted the difficulties in controlling this disease both in developed and in developing countries. Biosecurity is considered the most important tool to prevent and control AI. In certain areas of the world, AI has become endemic and the recent outbreaks in Europe and Africa show that the epidemiological situation is evolving in an unprecedented way. The consequences of this situation are economic losses to the poultry industry, food security issues in developing countries and a serious threat to human health, due to the direct consequences of AI infection in humans, and more alarmingly due to the risk of the generation of a new pandemic virus from the animal reservoir. In this paper, the physical and chemical methods of inactivating AI viruses are reviewed, with particular emphasis on the practicalities of using such methods in the poultry industry. PMID- 17348910 TI - Production and characterization of monoclonal antibodies to (poly100)S1 protein of avian infectious bronchitis virus. AB - Fragments within S1 genes ((poly100)S1) of infectious bronchitis virus (IBV) strains ZJ971, M41 and SC021202 (SC) were subcloned into a prokaryotic expression vector and expressed in Escherichia coli. Monoclonal antibodies (mAbs) against the recombinant (poly100)S1 proteins were produced, characterized and used to analyse epitopes on the S1 subunit of IBV. Nine mAbs raising from the three (poly100)S1 proteins recognized five different epitopes of the S1 subunit, designated as S1-A, B, C, D and E. Epitopes S1-C and S1-D are common for the three IBV strains, while S1-A and S1-B exist on ZJ971 and M41 strains, and S1-E was a strain-specific epitope for SC strain. Immunocytochemistry indicated that all the mAbs to the (poly100)S1 proteins can react with the homologous S1 glycoprotein expressed in Vero cells. Moreover neutralization test demonstrated that only mAbs 6E2, 4F9 and 6G4 had neutralization activity for the homologous IBV. These mAbs to (poly100)S1 protein were potential candidates for detecting and distinguishing IBV strains, and also used to examine antigenic variation of the S1 protein. PMID- 17348911 TI - Occurrence and characterization of verocytotoxigenic Escherichia coli (VTEC) strains from dairy farms in Trinidad. AB - A cross-sectional study was conducted to determine the prevalence and characteristics of verocytotoxigenic Escherichia coli (VTEC) on 25 dairy farms each located in Waller field and Carlsen field farming areas in Trinidad. On each selected farm, faecal samples were collected from milking cows, calves and humans; rectal swabs were obtained from pet farm dogs; bulk milk was sampled as well as effluent from the milking parlour. Escherichia coli was isolated from all sources on selective media using standard methods. Isolates of E. coli were subjected to slide agglutination test using E. coli O157 antiserum, vero cell cytotoxicity assay to detect verocytotoxin (VT) and heat labile toxin (LT) production, the polymerase chain reaction (PCR) to detect VT genes, and the dry spot test to screen for E. coli O157 and non-O157 strains. In addition, faecal samples from animal and human sources were tested for VT genes using PCR. Of a total of 933 E. coli isolates tested by the slide test, eight (0.9%) were positive for the O157 strain. The vero cell cytotoxicity assay detected VT producing strains of E. coli in 16.6%, 14.6%, 3.2% and 7.1% of isolates from cows, calves, farm dogs and humans respectively (P < 0.05; chi(2)). For LT production, the highest frequency was detected amongst isolates of E. coli from calves (10.8%) and the lowest (0.0%) amongst isolates from humans and bulk milk (P < 0.05; chi(2)). Of the 61 VT-producing isolates by vero cell cytotoxicity assay tested by PCR, the VT, LT and eae genes were detected in 62.3%, 4.9% and 1.6% respectively (P < 0.05; chi(2)). Amongst the 45 E. coli isolates that were VT positive (vero cell) or VT-gene positive by PCR, 2.2%, 2.2%, 4.4% and 6.7% belonged to non-O157 strains O91, O111, O103 and O157, respectively, as determined by the Dry spot test. Detection of VTEC strains in milk and dairy animals poses a health risk to consumers of milk originating from these farms. In addition, the demonstration of VTEC strains in humans, VT gene in faecal samples and E. coli isolates as well as non-O157 VTEC strains of E. coli are being documented for the first time in the country. PMID- 17348912 TI - Individual animals of a cattle herd infected with the same Mycobacterium bovis genotype shows important variations in bacteriological, histopathological and immune response parameters. AB - Cattle are the host and main reservoir of the etiologic agent of bovine tuberculosis, Mycobacterium bovis; although other mammalian species, including humans, are susceptible. The tuberculin test and/or slaughterhouse surveillance is the diagnostic method used by control programs all around the world to control and eradicate the disease. In order to compare different tuberculosis diagnostic tests and to reach disease confirmation, a study was performed in a group of 14 steers of Friesian breed, reacting positively to tuberculin test. Three ante mortem assays were performed according to the type of sample: the gamma interferon (IFN-gamma) test (which quantifies the release of this cytokine by sensitized lymphocytes in whole blood in response to purified protein derivative (PPD) and recombinant ESAT-6 and CFP10 proteins); PCR and bacteriologic culture from nasal swab and intradermal tuberculin test. These assays were taken at different times to assess the evolution of clinical parameters. Post-mortem examination showed macroscopic and microscopic tuberculosis lesions with acid fast bacillus and positive cultures. By spoligotyping, we observed that all the isolates showed the same pattern. The positive results based on comparison to lesions observed ranged from 58% to 75% for the IFN-gamma assays, to 72% for cultures, and ranged from 50% to 90% for PCR in nasal swabs. In conclusion, in a herd infected by the same strain, ante-mortem direct and immune-diagnostic parameters change, suggesting that several tests are needed for a faster control of infection at herd level. PMID- 17348913 TI - Anaplasma phagocytophilum in dogs in Germany. AB - A total number of 111 dogs were included in the present prospective study investigating the prevalence of Anaplasma phagocytophilum in dogs in Germany. Dogs were divided into two groups. Dogs of group 1 (n = 49) showed clinical and/or haematological signs seen in infections with A. phagocytophilum, whereas those of group 2 (n = 62) did not have any evidence of anaplasmosis. For each dog, an A. phagocytophilum 16S rRNA-nested polymerase chain reaction (PCR) of ethylenediaminetetraacetic acid (EDTA)-anticoagulated whole blood analysis, a microscopic evaluation of a buffy coat and a serum indirect fluorescent antibody test (IFAT) were performed. Forty-eight seroreactive dogs were identified altogether, which amounts to an overall point prevalence of 43.2%. There was no significant difference between the seroreactivity to A. phagocytophilum antigens among group 1 (44.9%) and 2 (41.9%) (P > 0.5). Seven dogs (6.3%) had positive PCR results. All of them were seroreactive. Six belonged to group 1. Morulae in neutrophilic granulocytes were found in two dogs of group 1 but in none of group 2. Both dogs were seroreactive. Very high antibody titres (> or =1:1024) were detected significantly more frequently in dogs with clinical signs attributable to infection with A. phagocytophilum (group 1) than in those without (group 2) (P < 0.001). There was no significant correlation of overall positives or antibody titres to age, breed, sex, or whether the dogs were family or working dogs. Dogs with high tick infestation were significantly more often seroreactive to A. phagocytophilum than those with no or low tick infestation (P = 0.007). In conclusion, there seems to be a high risk of infection with A. phagocytophilum in Germany. Results of this study suggest that severe illness solely caused by A. phagocytophilum may be possible although definitive evidence does not exist. Very high antibody titres (>1:1024) may be associated with clinical anaplasmosis. PMID- 17348914 TI - Estimating a geographically explicit model of population divergence. AB - Patterns of genetic variation can provide valuable insights for deciphering the relative roles of different evolutionary processes in species differentiation. However, population-genetic models for studying divergence in geographically structured species are generally lacking. Since these are the biogeographic settings where genetic drift is expected to predominate, not only are population genetic tests of hypotheses in geographically structured species constrained, but generalizations about the evolutionary processes that promote species divergence may also be potentially biased. Here we estimate a population-divergence model in montane grasshoppers from the sky islands of the Rocky Mountains. Because this region was directly impacted by Pleistocene glaciation, both the displacement into glacial refugia and recolonization of montane habitats may contribute to differentiation. Building on the tradition of using information from the genealogical relationships of alleles to infer the geography of divergence, here the additional consideration of the process of gene-lineage sorting is used to obtain a quantitative estimate of population relationships and historical associations (i.e., a population tree) from the gene trees of five anonymous nuclear loci and one mitochondrial locus in the broadly distributed species Melanoplus oregonensis. Three different approaches are used to estimate a model of population divergence; this comparison allows us to evaluate specific methodological assumptions that influence the estimated history of divergence. A model of population divergence was identified that significantly fits the data better compared to the other approaches, based on per-site likelihood scores of the multiple loci, and that provides clues about how divergence proceeded in M. oregonensis during the dynamic Pleistocene. Unlike the approaches that either considered only the most recent coalescence (i.e., information from a single individual per population) or did not consider the pattern of coalescence in the gene genealogies, the population-divergence model that best fits the data was estimated by considering the pattern of gene lineage coalescence across multiple individuals, as well as loci. These results indicate that sampling of multiple individuals per population is critical to obtaining an accurate estimate of the history of divergence so that the signal of common ancestry can be separated from the confounding influence of gene flow-even though estimates suggest that gene flow is not a predominant factor structuring patterns of genetic variation across these sky island populations. They also suggest that the gene genealogies contain information about population relationships, despite the lack of complete sorting of gene lineages. What emerges from the analyses is a model of population divergence that incorporates both contemporary distributions and historical associations, and shows a latitudinal and regional structuring of populations reminiscent of population displacements into multiple glacial refugia. Because the population-divergence model itself is built upon the specific events shaping the history of M. oregonensis, it provides a framework for estimating additional population-genetic parameters relevant to understanding the processes governing differentiation in geographically structured species and avoids the problems of relying on overly simplified and inaccurate divergence models. The utility of these approaches, as well as the caveats and future improvements, for estimating population relationships and historical associations relevant to genetic analyses of geographically structured species are discussed. PMID- 17348915 TI - Population differentiation in the beetleTribolium castaneum. I. Genetic architecture. AB - We used joint-scaling analyses in conjunction with rearing temperature variation to investigate the contributions of additive, non-additive, and environmental effects to genetic divergence and incipient speciation among 12 populations of the red flour beetle, Tribolium castaneum, with small levels of pairwise nuclear genetic divergence (0.033 < Nei's D < 0.125). For 15 population pairs we created a full spectrum of line crosses (two parental, two reciprocal F1's, four F2's, and eight backcrosses), reared them at multiple temperatures, and analyzed the numbers and developmental defects of offspring. We assayed a total of 219,388 offspring from 5147 families. Failed crosses occurred predominately in F2's, giving evidence of F2 breakdown within this species. In all cases where a significant model could be fit to the data on offspring number, we observed at least one type of digenic epistasis. We also found maternal and cytoplasmic effects to be common components of divergence among T. castaneum populations. In some cases, the most complex model tested (additive, dominance, epistatic, maternal, and cytoplasmic effects) did not provide a significant fit to the data, suggesting that linkage or higher order epistasis is involved in differentiation between some populations. For the limb deformity data, we observed significant genotype-by-environment interaction in most crosses and pure parent crosses tended to have fewer deformities than hybrid crosses. Complexity of genetic architecture was not correlated with either geographic distance or genetic distance. Our results support the view that genetic incompatibilities responsible for postzygotic isolation, an important component of speciation, may be a natural but serendipitous consequence of nonadditive genetic effects and structured populations. PMID- 17348916 TI - Analysis of character divergence along environmental gradients and other covariates. AB - Character displacement is typically identified by comparing phenotypic differences in sympatry and allopatry. Recently, however, Goldberg and Lande (2006) pointed out that when phenotypic characters vary along an environmental gradient, the standard approach may fail to identify sympatric character divergence. Here we present a general analytical procedure for identifying sympatric character divergence while accounting for phenotypic changes that covary with environmental variables. Our approach uses residual randomization from a generalized linear model, and allows the statistical comparison of sympatric phenotypic divergence to allopatric phenotypic divergence while accounting for phenotypic variation along a gradient. Through simulation we demonstrate that our approach correctly identifies patterns of sympatric character divergence when they are present, and does not identify such patterns when they are not. Our analytical approach complements and extends the suggestions of Goldberg and Lande (2006), by allowing a full statistical assessment of the varied patterns of character displacement along environmental gradients, or while accounting for other covariates and sources of variation. PMID- 17348917 TI - Genetic differentiation by sexual conflict. AB - Sexual conflict has been suggested as a general cause of genetic diversification in reproductive characters, and as a possible cause of speciation. We use individual-based simulations to study the dynamics of sexual conflict in an isolated diploid population with no spatial structure. To explore the effects of genetic details, we consider two different types of interlocus interaction between female and male traits, and three different types of intra-locus interaction. In the simulations, sexual conflict resulted in at least the following five regimes: (1) continuous coevolutionary chase, (2) evolution toward an equilibrium, (3) cyclic coevolution, (4) extensive genetic differentiation in female traits/genes only, and (5) extensive genetic differentiation in both male and female traits/genes. Genetic differentiation was hardly observed when the traits involved in reproduction were determined additively and interacted in a trait-by-trait way. When the traits interacted in a component-by-component way, genetic differentiation was frequently observed under relatively broad conditions. The likelihood of genetic differentiation largely depended on the number of loci and the type of within-locus dominance. With multiple loci per trait, genetic differentiation was often observed but sympatric speciation was typically hindered by recombination. Sympatric speciation was possible but only under restrictive conditions. Our simulations also highlight the importance of stochastic effects in the dynamics of sexual conflict. PMID- 17348918 TI - Sensory trade-offs predict signal divergence in Surfperch. AB - Unidirectional elaboration of male trait evolution (e.g., larger, brighter males) has been predicted by receiver bias models of sexual selection and empirically tested in a number of different taxa. This study identifies a bidirectional pattern of male trait evolution and suggests that a sensory constraint is driving this divergence. In this system, the inherent trade-off in dichromatic visual detection places limits on the direction that sensory biases may take and thus provides a quantitative test of the sensory drive model. Here I show that sensory systems with trade-offs in detection abilities produce bidirectional biases and that signal design properties match these biases. I combine species-specific measurements and ancestral estimates with visual detection modeling to examine biases in sensory and signaling traits across five fish species occupying optically diverse habitats in the Californian kelp forest. Species-specific divergence in visual pigments correlates with changes in environment and produces different sensory biases--favoring luminance (brightness) detection for some species and chromatic (color) detection for others. Divergence in male signals (spectral reflectance of orange, blue, and silver color elements) is predicted by each species' sensory bias: color divergence favors chromatic detection for species with chromatically biased visual systems, whereas species with luminance sensory biases have signals favoring luminance detection. This quantitative example of coevolution of communication traits varying in a bidirectional pattern governed by the environment is the first demonstration of sensory trade-offs driving signal evolution. PMID- 17348919 TI - Karyotypic diversity and speciation in Agrodiaetus butterflies. AB - That chromosomal rearrangements may play an important role in maintaining postzygotic isolation between well-established species is part of the standard theory of speciation. However, little evidence exists on the role of karyotypic change in speciation itself--in the establishment of reproductive barriers between previously interbreeding populations. The large genus Agrodiaetus (Lepidoptera: Lycaenidae) provides a model system to study this question. Agrodiaetus butterflies exhibit unusual interspecific diversity in chromosome number, from n= 10 to n= 134; in contrast, the majority of lycaenid butterflies have n= 23/24. We analyzed the evolution of karyotypic diversity by mapping chromosome numbers on a thoroughly sampled mitochondrial phylogeny of the genus. Karyotypic differences accumulate gradually between allopatric sister taxa, but more rapidly between sympatric sister taxa. Overall, sympatric sister taxa have a higher average karyotypic diversity than allopatric sister taxa. Differential fusion of diverged populations may account for this pattern because the degree of karyotypic difference acquired between allopatric populations may determine whether they will persist as nascent biological species in secondary sympatry. This study therefore finds evidence of a direct role for chromosomal rearrangements in the final stages of animal speciation. Rapid karyotypic diversification is likely to have contributed to the explosive speciation rate observed in Agrodiaetus, 1.6 species per million years. PMID- 17348920 TI - Geometric morphometric analyses provide evidence for the adaptive character of the Tanganyikan cichlid fish radiations. AB - The cichlids of East Africa are renowned as one of the most spectacular examples of adaptive radiation. They provide a unique opportunity to investigate the relationships between ecology, morphological diversity, and phylogeny in producing such remarkable diversity. Nevertheless, the parameters of the adaptive radiations of these fish have not been satisfactorily quantified yet. Lake Tanganyika possesses all of the major lineages of East African cichlid fish, so by using geometric morphometrics and comparative analyses of ecology and morphology, in an explicitly phylogenetic context, we quantify the role of ecology in driving adaptive speciation. We used geometric morphometric methods to describe the body shape of over 1000 specimens of East African cichlid fish, with a focus on the Lake Tanganyika species assemblage, which is composed of more than 200 endemic species. The main differences in shape concern the length of the whole body and the relative sizes of the head and caudal peduncle. We investigated the influence of phylogeny on similarity of shape using both distance-based and variance partitioning methods, finding that phylogenetic inertia exerts little influence on overall body shape. Therefore, we quantified the relative effect of major ecological traits on shape using phylogenetic generalized least squares and disparity analyses. These analyses conclude that body shape is most strongly predicted by feeding preferences (i.e., trophic niches) and the water depths at which species occur. Furthermore, the morphological disparity within tribes indicates that even though the morphological diversification associated with explosive speciation has happened in only a few tribes of the Tanganyikan assemblage, the potential to evolve diverse morphologies exists in all tribes. Quantitative data support the existence of extensive parallelism in several independent adaptive radiations in Lake Tanganyika. Notably, Tanganyikan mouthbrooders belonging to the C-lineage and the substrate spawning Lamprologini have evolved a multitude of different shapes from elongated and Lamprologus-like hypothetical ancestors. Together, these data demonstrate strong support for the adaptive character of East African cichlid radiations. PMID- 17348921 TI - Changes in mating system and social structure of the ant Petalomyrmex phylax are associated with range expansion in Cameroon. AB - Past climate shifts have led to major oscillations in species distributions. Hence historical contingencies and selective processes occurring during such phases may be determinants for understanding the forces that have shaped extant phenotypes. In the plant-ant Petalomyrmex phylax (Formicinae), we observed spatial variation in number of queens in mature colonies, from several queens (high polygyny) in the median part of its distribution to a moderate number of queens (weak polygyny) or even only a single queen (monogyny) in the southwesternmost populations. This variation did not correlate with indicators of variation in current nest site availability and colony turnover, the supposedly determinant selective forces acting on gyny in ants. We show here that the variation in social structure correlates with a historical process corresponding to a progressive colonization of coastal southern Cameroon by the ant. Using microsatellite markers, we observed a clear pattern of isolation by distance except for the southernmost populations. Measures of genetic variability that do not take into account allele size were at equilibrium in all except the southernmost populations, suggesting recent foundation of the latter. Measures of genetic diversity taking into account allele size showed a clinal north-south decrease in variance of allele size. We propose that southern populations have yet to regain allele size variance after bottlenecks associated with the foundation of new populations, and that this variance is regained over time. Hence variation in social structure mirrors an old but still active southward colonization process or metapopulation dynamics, possibly in association with an expansion of the rain forest habitat during the late Holocene. A low number of queens in ant colonies is typically associated with strong dispersal capacity. We therefore suggest that the initial founders of new populations belong to the monogynous to weakly polygynous phenotype, and that queen number progressively increases in older populations. PMID- 17348922 TI - The short legs of great apes: evidence for aggressive behavior in australopiths. AB - Early hominins, australopiths, were similar to most large primates in having relatively short hindlimbs for their body size. The short legs of large primates are thought to represent specialization for vertical climbing and quadrupedal stability on branches. Although this may be true, there are reasons to suspect that the evolution of short legs may also represent specialization for physical aggression. Fighting in apes is a behavior in which short legs are expected to improve performance by lowering the center of mass during bipedal stance and by increasing the leverage through which muscle forces can be applied to the ground. Among anthropoid primates, body size sexual dimorphism (SSD) and canine height sexual dimorphism (CSD) are strongly correlated with levels of male-male competition, allowing SSD and CSD to be used as indices of male-male aggression. Here I show that the evolution of hindlimb length in apes is inversely correlated with the evolution of SSD (R(2)= 0.683, P-value = 0.006) and the evolution of CSD (R(2)= 0.630, P-value = 0.013). In contrast, a significant correlation was not observed for the relationship between the evolution of hindlimb and forelimb lengths. These observations are consistent with the suggestion that selection for fighting performance has maintained relatively short hindlimbs in species of Hominoidea with high levels of male-male competition. Although australopiths were highly derived for striding bipedalism when traveling on the ground, they retained short legs compared to those of Homo for over two million years, approximately 100,000 generations. Their short legs may be indicative of persistent selection for high levels of aggression. PMID- 17348923 TI - Multiple mating in the Glanville fritillary butterfly: a case of within generation bet hedging? AB - Many hypotheses have been proposed to explain multiple mating in females. One of them is bet hedging, that is avoiding having no or very few offspring in any given generation, rather than maximizing the expected number of offspring. However, within-generation bet hedging is generally believed to be an unimportant evolutionary force, except in very small populations. In this study, we derive predictions of the bet-hedging hypothesis for a case in which local insect populations are often small, offspring performance varies, for example, due to inbreeding depression, and the groups of gregarious larvae have to exceed a threshold size before they are likely to survive throughout the larval stage. These conditions exist for populations of the Glanville fritillary butterfly (Melitaea cinxia), potentially making bet-hedging benefits larger than usual. We observed matings in a field cage, which allowed detailed observations under practically natural conditions, and analyzed genetic paternity of egg clutches laid by females under direct observation. The egg-laying and survival patterns are in line with the predictions, supporting the hypothesis that multiple mating in M. cinxia presents a rare case of within-generation bet hedging. PMID- 17348924 TI - The relative importance of different direct benefits in the mate choices of a field cricket. AB - Discussions about the evolution of female mating preferences have often suggested that females should express multiple strong preferences when different male traits are correlated with different mating benefits, yet few studies have directly tested this hypothesis by comparing the strength of female preferences for male traits known to be correlated with different benefits. In the variable field cricket, Gryllus lineaticeps, females receive fecundity and fertility benefits from mating with males with higher chirp rates and life-span benefits from mating with males with longer chirp durations. Although females prefer higher chirp rates and longer chirp durations when the other trait is held constant, it is possible that they give priority to one of these song traits when both vary. In this study, we examined the relative importance of chirp rate and chirp duration in female mate choice using single-stimulus presentations of songs that varied in both chirp rate and chirp duration. Females expressed both directional and stabilizing preferences based on chirp rate, responding most strongly to a chirp rate approximately one standard deviation above the population mean. Females did not express preferences based on chirp duration, and did not express correlational preferences. These results suggest that females may give priority to the reproductive benefits provided by males that produce higher chirp rates. PMID- 17348925 TI - How bright and how nasty: explaining diversity in warning signal strength. AB - The conspicuous displays that warn predators of defenses carried by potential prey have been of interest to evolutionary biologists from the time of Wallace and Darwin to the present day. Although most studies implicitly assume that these "aposematic" warning signals simply indicate the presence of some repellent defense such as a toxin, it has been speculated that the intensity of the signal might reliably indicate the strength of defense so that, for example, the nastiest prey might "shout loudest" about their unprofitability. Recent phylogenetic and empirical studies of Dendrobatid frogs provide contradictory views, in one instance showing a positive correlation between toxin levels and conspicuousness, in another showing a breakdown of this relationship. In this paper we present an optimization model, which can potentially account for these divergent results. Our model locates the optimal values of defensive traits that are influenced by a range of costs and benefits. We show that optimal aposematic conspicuousness can be positively correlated with optimal prey toxicity, especially where population sizes and season lengths vary between species. In other cases, optimal aposematic conspicuousness may be negatively correlated with toxicity; this is especially the case when the marginal costs of aposematic displays vary between members of different populations. Finally, when displays incur no allocation costs there may be no single optimum value for aposematic conspicuousness, rather a large array of alternative forms of a display may have equal fitness. PMID- 17348926 TI - An assessment of sperm survival in Drosophila melanogaster. AB - Recently published evidence based on cytological staining indicates that sperm die rapidly after being stored in female Drosophila melanogaster. However, measuring sperm death in this way has a potential artifact: the death of sperm owing to the extraction, mounting, and staining of sperm. Here we use a protocol that bypasses all of these potential extraneous mortality factors to test the hypothesis that there is high mortality of stored sperm in D. melanogaster. Contrary to the findings from cytological staining, our data indicates that mortality of stored sperm is quite low. PMID- 17348927 TI - Sperm competition and sex change: a comparative analysis across fishes. AB - Current theory to explain the adaptive significance of sex change over gonochorism predicts that female-first sex change could be adaptive when relative reproductive success increases at a faster rate with body size for males than for females. A faster rate of reproductive gain with body size can occur if larger males are more effective in controlling females and excluding competitors from fertilizations. The most simple consequence of this theoretical scenario, based on sexual allocation theory, is that natural breeding sex ratios are expected to be female biased in female-first sex changers, because average male fecundity will exceed that of females. A second prediction is that the intensity of sperm competition is expected to be lower in female-first sex-changing species because larger males should be able to more completely monopolize females and therefore reduce male-male competition during spawning. Relative testis size has been shown to be an indicator of the level of sperm competition, so we use this metric to examine evolutionary responses to selection from postcopulatory male-male competition. We used data from 116 comparable female-first sex-changing and nonhermaphroditic (gonochoristic) fish species to test these two predictions. In addition to cross-species analyses we also controlled for potential phylogenetic nonindependence by analyzing independent contrasts. As expected, breeding sex ratios were significantly more female biased in female-first sex-changing than nonhermaphroditic taxa. In addition, males in female-first sex changers had significantly smaller relative testis sizes that were one-fifth the size of those of nonhermaphroditic species, revealing a new evolutionary correlate of female first sex change. These results, which are based on data from a wide range of taxa and across the same body-size range for either mode of reproduction, provide direct empirical support for current evolutionary theories regarding the benefits of female-first sex change. PMID- 17348928 TI - The build up of mutation-selection- drift balance in laboratory Drosophila populations. AB - The build up of an equilibrium between mutation, selection, and drift in populations of moderate size is an important evolutionary issue, and can be critical in the conservation of endangered populations. We studied this process in two Drosophila melanogaster populations initially lacking genetic variability (C1 and C2) that were subsequently maintained during 431 or 165 generations with effective population size N(e) approximately 500 (estimated by lethal complementation analysis). Each population originated synchronously to a companion set of full-sib mutation accumulation (MA) lines, C1 and MA1 were derived from an isogenic origin and C2 and MA2 from a single MA1 line at generation 265. The results suggest that both C1 and C2 populations were close to the mutation-selection-drift balance for viability and bristle traits, and are consistent with a 2.5-fold increase of the mutation rate in C2 and MA2. Despite this increase, the average panmictic viability in C2 was only slightly below that of C1, indicating that the expressed loads due to segregating deleterious mutation were small, in agreement with the low deleterious mutation rate (0.015 0.045) previously reported for the MA1 lines. In C1, the nonlethal inbreeding depression rate for viability was 30% of that usually estimated in segregating populations. The genetic variance for bristles regenerated in C1 and C2 was moderately smaller than the average value reported for natural populations, implying that they have accumulated a substantial adaptive potential. In light of neutral and selective predictions, these results suggest that bristle additive variance was predominantly due to segregation of mutations with deleterious effects of the order of 10(-3), and is consistent with relatively weak causal stabilizing selection (V(s) approximately 30). PMID- 17348929 TI - Effects of population size and mutation rate on the evolution of mutational robustness. AB - It is often assumed that the efficiency of selection for mutational robustness would be proportional to mutation rate and population size, thus being inefficient in small populations. However, Krakauer and Plotkin (2002) hypothesized that selection in small populations would favor robustness mechanisms, such as redundancy, that mask the effect of deleterious mutations. In large populations, by contrast, selection is more effective at removing deleterious mutants and fitness would be improved by eliminating mechanisms that mask the effect of deleterious mutations and thus impede their removal. Here, we test whether these predictions are supported in experiments with evolving populations of digital organisms. Digital organisms are self-replicating programs that inhabit a virtual world inside a computer. Like their organic counterparts, digital organisms mutate, compete, evolve, and adapt by natural selection to their environment. In this study, 160 populations evolved at different combinations of mutation rate and population size. After 10(4) generations, we measured the mutational robustness of the most abundant genotype in each population. Mutational robustness tended to increase with mutation rate and to decline with population size, although the dependence with population size was in part mediated by a negative relationship between fitness and robustness. These results are independent of whether genomes were constrained to their original length or allowed to change in size. PMID- 17348930 TI - Host availability and the evolution of parasite life-history strategies. AB - Parasites exploit an inherently patchy resource, their hosts, which are discrete entities that may only be available for infection within a relatively short time window. However, there has been little consideration of how heterogeneities in host availability may affect the phenotypic or genotypic composition of parasite populations or how parasites may evolve to cope with them. Here we conduct a selection experiment involving an entomopathogenic nematode (Steinernema feltiae) and show for the first time that the infection rate of a parasite can evolve rapidly to maximize the chances of infecting within an environment characterized by the rate of host availability. Furthermore, we show that the parasite's infection rate trades off with other fitness traits, such as fecundity and survival. Crucially, the outcome of competition between strains with different infection strategies depends on the rate of host availability; frequently available hosts favor "fast" infecting nematodes, whereas infrequently available hosts favor "slow" infecting nematodes. A simple evolutionarily stable strategy (ESS) analysis based on classic epidemiological models fails to capture this behavior, predicting instead that the fastest infecting phenotype should always dominate. However, a novel model incorporating more realistic, discrete bouts of host availability shows that strain coexistence is highly likely. Our results demonstrate that heterogeneities in host availability play a key role in the evolution of parasite life-history traits and in the maintenance of phenotypic variability. Parasite life-history strategies are likely to evolve rapidly in response to changes in host availability induced by disease management programs or by natural dynamics in host abundance. Incorporating parasite evolution in response to host availability would therefore enhance the predictive ability of current epidemiological models of infectious disease. PMID- 17348931 TI - Evolutionary dynamics of vertebrate body mass range. AB - Change in body mass with time has been considered for many clades, often with reference to Cope's rule, which predicts a tendency to increase in body size. A more general rule, namely increase in the range of body mass with time, is analyzed here for vertebrates. The log range of log vertebrate body mass is shown to increase linearly and highly significantly with the log of duration of clade existence. The resulting regression equations are used to predict the origin age, initial body mass, and subsequent dynamics of body mass range for primate clades such as the New World monkeys (Platyrrhini, 32 million years ago, initial mass of 1.7 kg) and the Anthropoidea (57 million years ago, initial mass of 0.12 kg), tested against the primate fossil record. Using these methods, other major primate clades such as Lemuriformes and Adapoidea are also estimated to have originated in the Tertiary (63 and 64 million years ago, respectively), with only the Plesiadapiformes originating in the Cretaceous (83 million years ago). Similarities of body mass range between primate and other vertebrate sister groups are discussed. Linear relationships of log range and log duration are considered with respect to Brownian processes, with the expected regression coefficients from the latter explored through simulations. The observed data produce regression coefficients that overlap with or are higher than those under Brownian processes. Overall, the analyses suggest the dynamics of vertebrate body mass range in morphologically disparate clades are highly predictable over many tens of million years and that the dynamics of phenotypic characteristics can assist molecular clock and fossil models in dating evolutionary events. PMID- 17348932 TI - Population differentiation in the beetle Tribolium castaneum. II. Haldane'S rule and incipient speciation. AB - The heterogametic sex tends to be rare, absent, sterile, or deformed in F1 hybrid crosses between species, a pattern called Haldane's rule (HR). The introgression of single genes or chromosomal regions from one drosophilid species into the genetic background of another have shown that HR is most often associated with fixed genetic differences in inter-specific crosses. However, because such introgression studies have involved species diverged several hundred thousand generations from a common ancestor, it is not clear whether HR attends the speciation process or results from the accumulation of epistatically acting genes postspeciation. We report the first evidence for HR prior to speciation in crosses between two populations of the red flour beetle, Tribolium castaneum, collected 931 km apart in Colombia and Ecuador. In this cross, HR is manifested as an increase in the proportion of deformed males compared to females and the expression of HR is temperature dependent. Neither population, when crossed to a geographically distant population from Japan, exhibits HR at any rearing temperature. Using joint-scaling analysis and additional data from backcrosses and F2's, we find that the hybrid incompatibilities and the emergence of HR are concurrent processes involving interactions between X-linked and autosomal genes. However, we also find many examples of incompatibilities manifest by F2 and backcross hybrids but not by F1 hybrids and most incompatibilities are not sex different in their effects, even when they involve both X-autosomal interactions and genotype-by-environment interactions. We infer that incipient speciation in flour beetles can occur with or without HR and that significant hybrid incompatibilities result from the accumulation of epistatically acting gene differences between populations without differentially affecting the heterogametic sex in F1 hybrids. The temperature dependence of the incompatibilities supports the inference that genotype-by-environment interactions and adaptation to different environments contribute to the genetic divergence important to postzygotic reproductive isolation. PMID- 17348933 TI - Southern hospitality: a latitudinal gradient in gene flow in the marine environment. AB - In recent years population genetics and phylogeographic studies have become increasingly valuable tools for inferring both historical and present-day genetic patterns within marine species. Here, we take a comparative approach to population-level study, analyzing original mitochondrial DNA data from 969 individuals representing 28 chiton (Mollusca: Polyplacophora) species to uncover large-scale genetic patterns along the Pacific coast of North America. The data reveal a distinct latitudinal connectivity gradient among chitons: species that exist at lower latitudes tend to have more isolated populations. This trend appears to be a product of between-species differences; within species, no significant gradient in connectivity is observed. Lower average annual sea surface temperatures are hypothesized to contribute to longer larval duration (and by extension, greater connectivity) among lecithotrophic species, providing a mechanism for the observed positive correlation between gene flow and latitude. Because increased isolation among populations may lead to speciation, a latitudinal trend in gene flow may contribute to the increased species diversity observed at lower latitudes. PMID- 17348934 TI - Evolution of colorful display. AB - How the displays of bowerbirds have evolved has attracted widespread interest. Endler et al. (2005) analyzed color use in display in a subset of bowerbird species and generalized their results to all bowerbirds. Here we discuss problems with their analysis that calls into question their conclusions. For example, they state that bowerbirds do not use decorations that match their background, but this is not supported by their results. They reconstruct historical patterns of sexual dimorphism in plumage display using questionable methodology. The high lability of these display traits makes these reconstructions unreliable and, using accepted methods and acknowledging the lability problem, we were unable to support their conclusions. Their claim that plumage differences between sympatric species are due to character displacement is not supported by the available data. Their focus is on visual contrast as the cause for display color and we offer additional hypotheses that may contribute to explaining color use. We support studies of spectral analysis of display traits but urge greater care in using this information to reach conclusions about how colorful displays have evolved. PMID- 17348936 TI - A novel preference for an invasive plant as a mechanism for animal hybrid speciation. AB - Homoploid hybrid speciation--speciation via hybridization without a change in chromosome number--is rarely documented and poorly understood in animals. In particular, the mechanisms by which animal homoploid hybrid species become ecologically and reproductively isolated from their parents are hypothetical and remain largely untested by experiments. For the many host-specific parasites that mate on their host, choosing the right host is the most important ecological and reproductive barrier between these species. One example of a host-specific parasite is the Lonicera fly, a population of tephritid fruit flies that evolved within the last 250 years likely by hybridization between two native Rhagoletis species following a host shift to invasive honeysuckle. We studied the host preference of the Lonicera fly and its putative parent species in laboratory experiments. The Lonicera fly prefers its new host, introduced honeysuckle, over the hosts of both parental species, demonstrating the rapid acquisition of preference for a new host as a means of behavioral isolation from the parent species. The parent taxa discriminate against each other's native hosts, but both accept honeysuckle fruit, leaving the potential for asymmetric gene flow from the parent species. Importantly, this pattern allows us to formulate hypotheses about the initial formation of the Lonicera fly. As mating partners from the two parent taxa are more likely to meet on invasive honeysuckle than on their respective native hosts, independent acceptance of honeysuckle by both parents likely preceded hybridization. We propose that invasive honeysuckle served as a catalyst for the local breakdown of reproductive isolation between the native parent species, a novel consequence of the introduction of an exotic weed. We describe behavioral mechanisms that explain the initial hybridization and subsequent reproductive isolation of the hybrid Lonicera fly. These results provide experimental support for a combination of host shift and hybridization as a model for hybrid speciation in parasitic animals. PMID- 17348937 TI - Field and experimental evidence for competition's role in phenotypic divergence. AB - Resource competition has long been viewed as a major cause of phenotypic divergence within and between species. Theory predicts that divergence arises because natural selection favors individuals that are phenotypically dissimilar from their competitors. Yet, there are few conclusive tests of this key prediction. Drawing on data from both natural populations and a controlled experiment, this paper presents such a test in tadpoles of two species of spadefoot toads (Spea bombifrons and S. multiplicata). These two species show exaggerated divergence in trophic morphology where they are found together (mixed species ponds) but not where each is found alone (pure-species ponds), suggesting that they have undergone ecological character displacement. Moreover, in pure species ponds, both species exhibit resource polymorphism. Using body size as a proxy for fitness, we found that in pure-species ponds disruptive selection favors extreme trophic phenotypes in both species, suggesting that intraspecific competition for food promotes resource polymorphism. In mixed-species ponds, by contrast, we found that trophic morphology was subject to stabilizing selection in S. multiplicata and directional selection in S. bombifrons. A controlled experiment revealed that the more similar an S. multiplicata was to its S. bombifrons tankmate in resource use, the worse was its performance. These results indicate that S. multiplicata individuals that differ from S. bombifrons would be selectively favored in competition. Our data therefore demonstrate how resource competition between phenotypically similar individuals can drive divergence between them. Moreover, our results indicate that how competition contributes to such divergence may be influenced not only by the degree to which competitors overlap in resource use, but also by the abundance and quality of resources. Finally, our finding that competitively mediated disruptive selection may promote resource polymorphism has potentially important implications for understanding how populations evolve in response to heterospecific competitors. In particular, once a population evolves resource polymorphism, it may be more prone to undergo ecological character displacement. PMID- 17348938 TI - Selection promotes organ compartmentalization in HIV-1: evidence from gag and pol genes. AB - The existence of organ-specific human immunodeficiency virus type 1 (HIV-1) populations within infected hosts has been long lasting studied. Previous work established that population subdivision by organs occurs at the envelope env gene, but less is known about other genomic regions. Here, we used a population genetics approach to detect organ compartmentalization in proviral sequences of HIV-1 gag and pol genes. Significant population structure was found in pol (100% of cases) and gag (33%) pair-wise organ comparisons. The degree of compartmentalization positively correlated with the ratio of nonsynonymous to synonymous substitutions, and codons showing organ compartmentalization were more likely to be under significantly positive selection. This suggests that HIV-1 populations dynamically adapt to locally variable intra-host environments. In the case of pol gene, differential penetration of antiretroviral drugs might account for the observed pattern, whereas for gag gene, local selective pressures remain unexplored. PMID- 17348939 TI - Rates of molecular evolution in bacteria are relatively constant despite spore dormancy. AB - Rates of molecular evolution are known to vary considerably among lineages, partially due to differences in life-history traits such as generation time. The generation-time effect has been well documented in some eukaryotes, but its prevalence in prokaryotes is unknown. "Because many species of Firmicute bacteria spend long periods of time as metabolically dormant spores, which could result in fewer DNA substitutions per unit time, they present an excellent system for testing predictions of the molecular clock hypothesis." To test whether spore forming bacteria evolve more slowly than their non-spore-forming relatives, I used phylogenetic methods to determine if there were differences in rates of amino acid substitution between spore-forming and non-spore-forming lineages of Firmicute bacteria. Although rates of evolution do vary among lineages, I find no evidence for an effect of spore-formation on evolutionary rate and, furthermore, evolutionary rates are similar to those calculated for enteric bacteria. These results support the notion that variation in generation time does not affect evolutionary rates in bacterial lineages. PMID- 17348940 TI - Sequence evolution of the sperm ligand zonadhesin correlates negatively with body weight dimorphism in primates. AB - Sexual selection has repeatedly been shown to be the probable driving force behind the positive Darwinian evolution of genes affecting male reproductive success. Here we compare the sequence evolution of the sperm ligand zonadhesin with body mass dimorphism in primates. In contrast to previous related studies, the present approach takes into account not only catarrhine primates, but also platyrrhines and lemurs. In detail, we analyze the sequence evolution of concatenated zonadhesin fragments (555 bp) of four Lemuroidea, five Platyrrhini, and seven Catarrhini, using the rate ratio of nonsynonymous to synonymous substitutions (dn/ds=omega). Unexpectedly, subsequent regression analyzes between omega estimates for the terminal branches of a primate phylogeny and residual male body mass reveal that sequence evolution of zonadhesin decreases with increasing sexual dimorphism in body weight. Mapping published mating system classifications onto these results illustrates that unimale breeding species show a tendency for rather slow sequence evolution of zonadhesin and comparably pronounced sexual dimorphism in body weight. Female choice and sperm competition can be assumed to drive the evolution of zonadhesin. We speculate that the level of sperm competition is lower in more sexually dimorphic primates because males of these species monopolize access to fertile females more successfully. Thus, variation in sperm competition may be driving the observed negative correlation of sequence evolution and sexual dimorphism in body weight. PMID- 17348941 TI - Testing for unequal rates of morphological diversification in the absence of a detailed phylogeny: a case study from Characiform fishes. AB - This study develops the random phylogenies rate test (RAPRATE), a likelihood method that simulates morphological evolution along randomly generated phylogenies, and uses it to determine whether a considerable difference in morphological diversity between two sister clades of South American fishes should be taken as evidence of differing rates of morphological change or lineage turnover. Despite identical ages of origin, similar species richness, and sympatric geographic distributions, the morphological and ecological diversity of the superfamily Anostomoidea exceeds that of the Curimatoidea. The test shows with 90% confidence (using variance among species as the measure of morphological diversity) or 99% confidence (using volume of occupied morphospace) that the rate of morphological change per unit time in the Anostomoidea likely exceeded that of the Curimatoidea. Variation in the rate of lineage turnover (speciation and extinction rates) is not found to affect greatly the morphological diversity of simulated clades and is not a likely explanation of the observed difference in morphological diversity in this case study. Though a 17% or greater delay in the onset of diversification in the Curimatoidea remains a possible alternative explanation of unequal morphological diversification, further simulations suggest that two clades drawn from the possible treespace of the Anostomoidea and Curimatoidea will rarely differ so greatly in the onset of diversification. Several uniquely derived morphological and ecological features of the Anostomoidea and Curimatoidea may have accelerated or decelerated their rate of morphological change, including a marked lengthening of the quadrate that may have relaxed structural constraints on the evolution of the anostomoid jaw. PMID- 17348942 TI - Statistical tests for taxonomic distinctiveness from observations of monophyly. AB - The observation of monophyly for a specified set of genealogical lineages is often used to place the lineages into a distinctive taxonomic entity. However, it is sometimes possible that monophyly of the lineages can occur by chance as an outcome of the random branching of lineages within a single taxon. Thus, especially for small samples, an observation of monophyly for a set of lineages- even if strongly supported statistically--does not necessarily indicate that the lineages are from a distinctive group. Here I develop a test of the null hypothesis that monophyly is a chance outcome of random branching. I also compute the sample size required so that the probability of chance occurrence of monophyly of a specified set of lineages lies below a prescribed tolerance. Under the null model of random branching, the probability that monophyly of the lineages in an index group occurs by chance is substantial if the sample is highly asymmetric, that is, if only a few of the sampled lineages are from the index group, or if only a few lineages are external to the group. If sample sizes are similar inside and outside the group of interest, however, chance occurrence of monophyly can be rejected at stringent significance levels (P < 10(-5)) even for quite small samples (approximately 20 total lineages). For a fixed total sample size, rejection of the null hypothesis of random branching in a single taxon occurs at the most stringent level if samples of nearly equal size inside and outside the index group--with a slightly greater size within the index group- are used. Similar results apply, with smaller sample sizes needed, when reciprocal monophyly of two groups, rather than monophyly of a single group, is of interest. The results suggest minimal sample sizes required for inferences to be made about taxonomic distinctiveness from observations of monophyly. PMID- 17348943 TI - Build-up of the Himalayan avifauna through immigration: a biogeographical analysis of the Phylloscopus and Seicercus warblers. AB - The Himalayan mountain range is one of the most species-rich areas in the world, harboring about 8% of the world's bird species. In this study, we compare the relative importance of immigration versus in situ speciation to the build-up of the Himalayan avifauna, by evaluating the biogeographic history of the Phylloscopus/Seicercus warblers, a speciose clade that is well represented in Himalayan forests. We use a comprehensive, multigene phylogeny in conjunction with dispersal-vicariance analysis to discern patterns of speciation and dispersal within this clade. The results indicate that virtually no speciation has occurred within the Himalayas. Instead, several speciation events are attributed to dispersal into the Himalayas followed by vicariance between the Himalayas and China/Southeast Asia. Most, perhaps all, of these events appear to be pre-Pleistocene. The apparent lack of speciation within the Himalayas stands in contrast to the mountain-driven Pleistocene speciation suggested for the Andes and the East African mountains. PMID- 17348944 TI - Historical range expansion determines the phylogenetic diversity introduced during contemporary species invasion. AB - For a species rapidly expanding its geographic range, such as during biological invasion, most alleles in the introduced range will have their evolutionary origins in the native range. Yet, the way in which historical processes occurring over evolutionary time in the native range contribute to the diversity sampled during contemporary invasion is largely unknown. We used chloroplast DNA (cpDNA) gene genealogies and coalescent methods to study two congeneric plants, Silene latifolia and S. vulgaris. We examined how phylogenetic diversity was shaped by demographic growth and historical range expansions in the native European range, and how this history affected the diversity sampled during their recent invasion of North America. Genealogies from both species depart from neutrality, likely as a result of demographic expansion in the ancestral range, the timing of which corresponds to shortly after each species originated. However, the species differ in the spatial distribution of cpDNA lineages across the native range. Silene latifolia shows a highly significant phylogeographic structure that most likely reflects different avenues of the post-glacial expansion into northern Europe from Mediterranean refugia. By contrast, cpDNA lineages in S. vulgaris have been widely scattered across Europe during, or since, the most recent post-glacial expansion. These different evolutionary histories resulted in dramatic differences in how phylogenetic diversity was sampled during invasion of North America. In S. latifolia, relatively few, discrete invasion events from a structured native range resulted in a rather severe genetic bottleneck, but also opportunities for admixture among previously isolated lineages. In S. vulgaris, lack of genetic structure was accompanied by more representative sampling of phylogenetic diversity during invasion, and reduced potential for admixture. Our results provide clear insights into how historical processes may feed forward to influence the phylogenetic diversity of species invading new geographic ranges. PMID- 17348945 TI - Evolution into and out of the Andes: a Bayesian analysis of historical diversification in Thamnophilus antshrikes. AB - The Andean uplift played important roles in the historical diversification of Neotropical organisms, both by producing new high-elevation habitats that could be colonized and by isolating organisms on either side of the mountains. Here, we present a molecular phylogeny of Thamnophlius antshrikes, a clade of 30 species whose collective distribution spans nearly the entirety of lowland habitats in tropical South America, the eastern slope foothills of the Andes, and the tepuis of northern South America. Our goal was to examine the role of the Andes in the diversification of lowland and foothill species. Using parsimony and Bayesian ancestral state reconstructions of a three-state distribution character (lowland restricted, lowland-to-highland, highland-restricted), we found that the Andes were colonized twice independently and the tepuis once from lowland-restricted ancestors. Over the entire evolutionary history of Thamnophilus, the highest transition rates were between highland-restricted and lowland-to-highland distributions, with extremely low rates into and out of lowland-restricted distributions. This pattern suggests lowland-restricted distributions are limited not by physiological constraints, but by other forces, such as competition. These results highlight the need for additional comparative studies in elucidating processes associated with the colonization of high-elevation habitats and the differentiation of populations within them. PMID- 17348946 TI - Polygenic traits and parasite local adaptation. AB - The extent to which parasites are locally adapted to their hosts has important implications for human health and agriculture. A recently developed conceptual framework--the geographic mosaic theory of coevolution--predicts that local maladaptation should be common and largely determined by the interplay between gene flow and spatially variable reciprocal selection. Previous investigation of this theory has predominately focused on genetic systems of infection and resistance characterized by few genes of major effect and particular forms of epistasis. Here we extend existing theory by analyzing mathematical models of host-parasite interactions in which host resistance to parasites is mediated by quantitative traits with an additive polygenic basis. In contrast to previous theoretical studies predicated upon major gene mechanisms, we find that parasite local maladaptation is quite uncommon and restricted to one specific functional form of host resistance. Furthermore, our results show that local maladaptation should be rare or absent in studies that measure local adaptation using reciprocal transplant designs conducted in natural environments. Our results thus narrow the scope over which the predictions of the geographic mosaic theory are likely to hold and provide novel and readily testable predictions about when and where local maladaptation is expected. PMID- 17348947 TI - Natural selection on a polymorphic disease-resistance locus in Ipomoea purpurea. AB - Although disease-resistance polymorphisms are common in natural plant populations, the mechanisms responsible for this variation are not well understood. Theoretical models predict that balancing selection can maintain polymorphism within a population if the fitness effects of a resistance allele vary from a net cost to a net benefit, depending upon the extent of pathogen damage. However, there have been a few attempts to determine how commonly this mechanism operates in natural plant-pathogen interactions. Ipomoea purpurea populations are often polymorphic for resistance and susceptibility alleles at a locus that influences resistance to the fungal pathogen, Coleosporium ipomoeae. We measured the fitness effects of resistance over three consecutive years at natural and manipulated levels of damage to characterize the type of selection acting on this locus. Costs of resistance varied in magnitude from undetectable to 15.5%, whereas benefits of resistance sometimes equaled, but never exceeded, these costs. In the absence of net benefits of resistance at natural or elevated levels of disease, we conclude that selection within individual populations of I. purpurea probably does not account completely for maintenance of this polymorphism. Rather, the persistence of this polymorphism is probably best explained by a combination of variable selection and meta-population processes. PMID- 17348948 TI - Domestication of maize, sorghum, and sugarcane did not drive the divergence of their smut pathogens. AB - We investigated two alternative hypotheses for the origin of crop pathogen species: that human-mediated agricultural practices drove the divergence of many crop plant pathogen species or that coevolutionary processes in natural populations of the crops' ancestors drove divergence of pathogen species. We distinguished between these two hypotheses by constructing a robust multigene phylogeny and estimating the dates of divergence among four, monophyletic species of smut fungi (Ustilago maydis, U. scitaminea, Sporisorium reilianum, S. sorghi) known to specifically infect maize, sorghum, sugarcane, and their wild ancestors. Without a fossil record for smut fungi, we calibrated the pathogen species' divergence times to their plant host divergence times. Specifically, a calibration date of 10,000 years was employed to test the hypothesis that the fungal species originated at the time of domestication of their current hosts and a calibration date of 50 million years was employed to test the hypothesis that the fungal species originated on wild ancestors of their domesticated hosts. Substitution rates at five protein coding genes were calculated and rates obtained for the 10,000 year calibration date were orders of magnitude faster than those commonly reported for eukaryotes, thus rejecting the hypothesis that these smut pathogen species diverged at the time of domestication. In contrast, substitution rates obtained for the 50 million year calibration were comparable to eukaryotic substitution rates. We used the 50 million year calibration to estimate divergence times of taxa in two datasets, one comprised solely the focal species and one comprised the focal species and additional related taxa. Both datasets indicate that all taxa diverged millions of years ago, strongly supporting the hypothesis that smut species diverged before the time of domestication and modern agriculture. Thus, smut species diverged in the ecological context of natural host plant and fungal populations. PMID- 17348949 TI - The role of male flowers in andromonoecious species: energetic costs and siring success in Solanum carolinense L. AB - Two non-mutually exclusive hypotheses regarding the benefits of andromonoecy (producing perfect and female-sterile flowers on the same plant) are tested using Solanum carolinense. Results indicate that (1) staminate flowers are cheaper to produce than perfect flowers, even after correcting for their relative position in the inflorescence; (2) the resources saved by producing staminate flowers are not re-allocated to other fitness enhancing functions; and (3) the main morphological characteristic of staminate flowers, pistil reduction, does not increase either pollinator visitation or siring success of open-pollinated plants. These results indicate that neither the resource savings hypothesis nor the increased pollen donation hypothesis explains the evolution and maintenance of andromonoecy in S. carolinense. PMID- 17348950 TI - The evolution of multiple mating in army ants. AB - The evolution of mating systems in eusocial Hymenoptera is constrained because females mate only during a brief period early in life, whereas inseminated queens and their stored sperm may live for decades. Considerable research effort during recent years has firmly established that obligate multiple mating has evolved only a few times: in Apis honeybees, Vespula wasps, Pogonomyrmex harvester ants, Atta and Acromyrmex leaf-cutting ants, the ant Cataglyphis cursor, and in at least some army ants. Here we provide estimates of queen-mating frequency for New World Neivamyrmex and Old World Aenictus species, which, compared to other army ants, have relatively small colonies and little size polymorphism among workers. To provide the first overall comparative analysis of the evolution of army ant mating systems, we combine these new results with previous estimates for African Dorylus and New World Eciton army ants, which have very large colonies and considerable worker polymorphism. We show that queens of Neivamyrmex and Aenictus mate with the same high numbers of males (usually ca. 10-20) as do queens of army ant species with very large colony sizes. We infer that multiple queen mating is ancestral in army ants and has evolved over 100 million years ago as part of the army ant adaptive syndrome. A comparison of army ants and honeybees suggests that mating systems in these two distantly related groups may have been convergently shaped by strikingly similar selective pressures. PMID- 17348951 TI - Incestuous mate preference by a simultaneous hermaphrodite with strong inbreeding depression. AB - Inbreeding depression and its consequences for mate choice have been extensively studied in free-living animals. However, very little is known about its significance for parasites, although it is well recognized that the mating systems of parasites can have important implications for their epidemiology and evolution. In this article, we show that the cestode Schistocephalus solidus shows incestuous mate preference despite evidence for very strong inbreeding depression. When given the simultaneous choice between mating with a sibling and an unrelated partner, on average, the cestode preferred its sibling. To explain this surprising result, we present three hypotheses that suggest different benefits to fitness of incestuous mating, which could, alone or in concert, outweigh the cost of inbreeding depression. PMID- 17348952 TI - Male courtship attractiveness and paternity success in Photinus greeni fireflies. AB - Although female mate choice and male sperm competition have separately attracted much attention, few studies have addressed how precopulatory and postcopulatory episodes of sexual selection might interact to drive the evolution of male traits. In Photinus fireflies, females preferentially respond to males based on their bioluminescent courtship signals, and females gain direct benefits through male nuptial gifts acquired during multiple matings over several nights. We experimentally manipulated matings of P. greeni fireflies to test the hypothesis that postcopulatory paternity success might be biased toward males that are more attractive during courtship interactions. We first measured male courtship attractiveness to individual females using field behavioral assays. Females were then assigned to two double-mating treatments: (1) least attractive second male females were first mated with their most attractive male, followed by their least attractive male, or (2) most attractive second male-females mated with males in reverse order. Larval offspring produced by each female following these double matings were genotyped using random amplified polymorphic DNA (RAPD) markers, and male paternity was determined. Contrary to prediction, firefly males that were more attractive to females based on their bioluminescent courtship displays subsequently showed significantly lower paternity, reflecting possible male trade offs or sexual conflict. Differences in male paternity were not related to male body condition, testes or accessory gland mass, or to variation in female spermathecal size. Additionally, this study suggests that changes in phenotypic selection gradients may occur during different reproductive stages. These results indicate that it is crucial for future studies on sexual selection in polyandrous species to integrate both precopulatory and postcopulatory episodes to fully understand the evolution of male traits. PMID- 17348953 TI - Rapid adaptation to a novel host in a seed beetle (Callosobruchus maculatus): the role of sexual selection. AB - Rapid diversification is common among herbivorous insects and is often the result of host shifts, leading to the exploitation of novel food sources. This, in turn, is associated with adaptive evolution of female oviposition behavior and larval feeding biology. Although natural selection is the typical driver of such adaptation, the role of sexual selection is less clear. In theory, sexual selection can either accelerate or impede adaptation. To assess the independent effects of natural and sexual selection on the rate of adaptation, we performed a laboratory natural selection experiment in a herbivorous bruchid beetle (Callosobruchus maculatus). We established replicated selection lines where we varied natural (food type) and sexual (mating system) selection in a 2 x 2 orthogonal design, and propagated our lines for 35 generations. In half of the lines, we induced a host shift whereas the other half was kept on the ancestral host. We experimentally enforced monogamy in half of the lines, whereas the other half remained polygamous. The beetles rapidly adapted to the novel host, which primarily involved increased host acceptance by females and an accelerated rate of larval development. We also found that our mating system treatment affected the rate of adaptation, but that this effect was contingent upon food type. As beetles adapted to the novel host, sexual selection reinforced natural selection whereas populations residing close to their adaptive peak (i.e., those using their ancestral host) exhibited higher fitness in the absence of sexual selection. We discuss our findings in light of current sexual selection theory and suggest that the net evolutionary effect of reproductive competition may critically depend on natural selection. Sexual selection may commonly accelerate adaptation under directional natural selection whereas sexual selection, and the associated load brought by sexual conflict, may tend to depress population fitness under stabilizing natural selection. PMID- 17348954 TI - The causes of variation in tree seedling traits: the roles of environmental selection versus chance. AB - A key aspect of biodiversity is the great quantitative variation in functional traits observed among species. One perspective asserts that trait values should converge on a single optimum value in a particular selective environment, and consequently trait variation would reflect differences in selective environment, and evolutionary outcomes would be predictable. An alternative perspective asserts that there are likely multiple alternative optima within a particular selective environment, and consequently different lineages would evolve toward different optima due to chance. Because there is evidence for both of these perspectives, there is a long-standing controversy over the relative importance of convergence due to environmental selection versus divergence due to chance in shaping trait variation. Here, I use a model of tree seedling growth and survival to distinguish trait variation associated with multiple alternative optima from variation associated with environmental differences. I show that variation in whole plant traits is best explained by environmental differences, whereas in organ level traits variation is more affected by alternative optima. Consequently, I predict that in nature variation in organ level traits is most closely related to phylogeny, whereas variation in whole plant traits is most closely related to ecology. PMID- 17348955 TI - Egg-hatching benefits gained by polyandrous female locusts are not due to the fertilization advantage of nonsibling males. AB - Several studies suggest that polyandrous females bias paternity in favor of unrelated males to avoid inbreeding depression. Here we tested whether the migratory locust biases sperm usage toward unrelated males by analyzing the paternity of offspring from females mated with either two siblings, or two nonsiblings, or a sibling and a nonsibling in either order. We found that the eggs of females mated only with siblings had decreased hatching success. When females mated with both a nonsibling and a sibling, egg hatchability was significantly increased. Subsequent paternity analyses found no evidence that females could avoid fertilization by sibling males. Therefore, improvement of the hatchability of eggs sired by siblings suggests that rather than biased fertilization by females toward genetically compatible or superior males, male induced maternal effects or direct effects of male ejaculates might influence the survival of offspring sired by related males. PMID- 17348956 TI - Throwing the baby out with the bathwater? A lateral view of nursing research. PMID- 17348957 TI - Schizophrenia housing and supportive relationships. AB - Schizophrenia can be a very disabling illness that affects between 0.5% and 1% of the population. This illness has a great personal impact on the individual sufferer, their family and friends. In addition, it makes significant demands on health services and the community in general. This paper reviews the literature on housing and supportive relationships for people with schizophrenia. The literature reports that people's experience of their schizophrenia is that it not only causes symptoms, but often impacts on their ability to maintain the basic resources in life. These resources include the ability to maintain reasonable quality housing, which seems to further impact negatively on their illness and their ability to maintain supportive social relationships. People with schizophrenia (and people in general) rely on their social relationships and family to maintain their mental health. The loss of social relationships and inability to maintain quality housing seem to be related - if people cannot maintain quality housing, they find it difficult to maintain supportive social relationships. PMID- 17348958 TI - Prevalence of disruptive behaviour displayed by older people in community and residential respite care settings. AB - The aim of this study was to determine the prevalence of disruptive behaviour displayed by older people in community and residential respite care settings. The specific objectives were to (i) obtain an estimate of the frequency of disruptive behaviour displayed by older people in the community setting before residential respite care; (ii) characterize older people being admitted for residential respite care; and (iii) obtain an estimate of the frequency of disruptive behaviour displayed by older people in residential respite care. A quantitative approach using a cross-sectional survey was employed in the community and in the residential aged care facilities. The older people (n = 100) had a mean age of 81.8 years (range 66-96 years). The older people were being admitted from their homes for booked respite care at residential aged care facilities in a regional Australian city. Home caregivers and nurses rated disruptive behaviour using the Dementia Behaviour Disturbance Scale (DBDS). Reliability data for the DBDS are provided. As expected, in both community and residential respite settings, older people with dementia (29%) scored significantly higher on the DBDS than people without dementia. In addition, DBDS scores were unexpectedly higher in the community setting than in the respite setting. These findings should be taken into consideration by primary health-care professionals when offering treatment options to the home caregivers and by staff in the residential aged care facilities that offer respite. PMID- 17348959 TI - Caregiver burden and coping patterns of Chinese parents of a child with a mental illness. AB - The burden of providing care to a family member, who has a mental illness, has been investigated in the past. However, limited research has focused on how parents cope, as they attempt to maintain a functional family life, when they have a child with a mental illness. This study explored, using a descriptive correlational design, the: (i) differences between parents of a child with mental illness, regarding caregiver burden, coping patterns, and demographic characteristics; (ii) effect parental educational level, parental working status, educational level of the child, diagnosis of the child, and family economic status have on parental caregiver burden and coping patterns; (iii) relationships among caregiver burden and coping patterns; and (iv) demographic characteristics of parents and children that predict caregiver burden and parental coping patterns. Data were collected via interview using structured questionnaires, from 97 mainland Chinese parents who had a child with a mental illness. The findings revealed the parents perceived significant caregiver burden, while caring for their child with a mental illness, yet used limited coping patterns to maintain a functional family life. Also, a significant negative correlation was found between the parents' caregiver burden and the way of coping. Parental physical health and the child's educational level were the best predictors of caregiver burden, while parental physical health and educational levels were the best predictors of the way of coping. Findings suggest that effective nursing interventions should be instituted to help parents of a child with mental illness cope with caregiver burden, while maintaining a functional family life. PMID- 17348960 TI - Factors influencing the use and provision of respite care services for older families of people with a severe mental illness. AB - Family carers of people with a severe mental illness play a vital, yet often unrecognized and undervalued role in Australian society. Respite care services can assist these family carers in their role; however, little is known about their access to these services. The paper addresses this knowledge gap. An exploratory field study was conducted throughout the eastern suburbs of Sydney, Australia, to identify and examine the factors influencing the use and provision of respite services for older carers of people with a mental illness. Semistructured, in-depth interviews, and structured self-completed questionnaires were conducted with older family carers, mental health care professionals, and respite care service providers. Additionally, relevant documents (local policies, strategic plans and reports on respite care) were reviewed. It was found that current respite services are problematic for older family carers of Australians with a mental illness, signalling the need for concerted efforts by carers, health professionals, and service providers to improve access. Changes to respite provision and utilization are recommended. PMID- 17348961 TI - Measuring melancholy: a critique of the Beck Depression Inventory and its use in mental health nursing. AB - The Beck Depression Inventory (BDI) is one of the most commonly used depression measurement instruments. Mental health nurses often utilize the BDI to assess the level of depression in clients, and to monitor the effectiveness of treatments such as antidepressants and electroconvulsive therapy. Despite the widespread use of the BDI in both clinical practice and research, there is surprisingly little nursing literature critically examining the BDI or its use by mental health nurses. This paper reviews the origins, purpose, and format of the BDI, discusses some of the strengths and limitations of the BDI, and concludes with some implications for mental health nursing. PMID- 17348962 TI - Impact of theory and clinical placement on undergraduate students' mental health nursing knowledge, skills, and attitudes. AB - Mental health issues are common and contemporary nursing students need to be well prepared to meet the mental health care needs of Australians. This study explored the influence of the mental health component of a Bachelor of Nursing course on second-year undergraduate nursing students' self-reported knowledge, skills, and attitudes in relation to mental health nursing. The study used a quasiexperimental research design involving questionnaires and individual interviews to determine nursing students' self-reported knowledge, skills, attitudes. Questionnaires were administered prior to undertaking the mental health theory, repeated prior to undertaking a clinical placement in either a community or inpatient mental health setting, and again after the clinical placement. The findings of the study indicated that a positive clinical placement had the greatest influence on nursing students' self-reported knowledge, skills, and attitudes and interest in nursing people experiencing mental health problems; however, the quantity of theoretical education also emerged as an influencing variable. PMID- 17348963 TI - Emergency department from the mental health client's perspective. AB - General hospital emergency departments (EDs) are obvious places for individuals in psychiatric distress or a mental health crisis to seek assistance. However, the typical mental health presentation does not fit with the treatment norm of most EDs creating a tension around the care of individuals with mental illnesses. Eight focus groups were held with mental health patients and their families to determine their satisfaction with care received in regional EDs with particular emphasis on their evaluation of the role of the psychiatric emergency nurse. Themes identified were: waiting in the ED, attitudes of treatment staff, diagnostic overshadowing, 'no where else to go', family needs, and a wish list for ideal services. These issues are described in this paper along with clinical and systemic implications. PMID- 17348964 TI - Caring as a resilient practice in mental health nursing. AB - This paper will develop a discussion about caring as a modern mental health nurse. We argue that the demands of mental health nursing today extend beyond the more traditional skills of care and caring. We believe that in order to meet mental health needs in the 21st century that caring should be extended to encompass the additional expertise of emotional intelligence and resilience. Emotional intelligence, resilience, and resilient behaviours have the potential to assist individuals to transcend negative experiences and transform these experiences into positive self-enhancing ones. This has implications for improved consumer outcomes through role-modelling and educational processes, but also may hold implications in supporting a strong workforce in mental health. PMID- 17348965 TI - Working with stories in nursing research: procedures used in narrative analysis. AB - This paper describes the procedures undertaken in a qualitative study that used nurses' stories to examine the influence of Gestalt therapy training on the professional practice of psychiatric nurses. The paper places narrative research methodologies within a nursing context before introducing narrative inquiry, specifically narrative analysis methodology. Procedures used in the study are subsequently described in sufficient detail to serve as a guide for novice researchers interested in undertaking a narrative analysis study. An exemplar of a storied outcome is provided to evidence the product of the narrative analysis research process. The paper concludes with reflections on the importance of articulating the process of narrative analysis as a means of developing interest and competence in narrative research, and using nurses' stories as a means of exploring, understanding, and communicating nursing practice. PMID- 17348966 TI - Sperm distribution in the reproductive tract of sows after intrauterine insemination. AB - The purpose of the present study was to compare the number of spermatozoa obtained from different parts of the oviducts and the uterine horns of sows after intrauterine insemination (IUI) and conventional artificial insemination (AI), 24 h after insemination. Twelve crossbred (Landrace x Yorkshire) multiparous sows were used in the experiment. The sows were examined for standing oestrus using a back pressure test and were examined every 4 h after standing oestrus by real time B-mode ultrasonography to estimate the time of ovulation. The sows were allocated to two groups, group I sows (n = 6) were inseminated by a conventional AI technique with 3 x 10(9) motile spermatozoa in 100 ml of extended semen, and group II sows (n = 6) were inseminated by an IUI technique using 1 x 10(9) motile spermatozoa in 50 ml of extended semen. A single dose of AI or IUI was given using the same boar, 8-10 h before the expected time of ovulation during the second oestrus after weaning. Twenty four hours after insemination, the sows were ovario-hysterectomized. The oviducts and the uterine horns were removed and divided into seven parts, the cranial, middle and caudal uterine horns, the utero tubal junction (UTJ), the cranial and caudal isthmus, and the ampulla. All parts of the reproductive tract were flushed and the spermatozoa were counted using a haemocytometer. The results revealed that the spermatozoa were found in both the oviducts and the uterine horns in all animals. The number of flushed spermatozoa in the UTJ of groups I and II, was 142,500 and 131,167 (p > 0.05), and in the caudal isthmus was 1411 and 1280 (p > 0.05), respectively. The proportion of spermatozoa in different parts of the reproductive tract in relation to the total number of spermatozoa within the tract was not significantly different between groups I and II (p > 0.05). It could be concluded that IUI, with a three-time reduction in the number of spermatozoa used resulted in the same number of spermatozoa to be deposited in the sperm reservoir around ovulation time. PMID- 17348967 TI - Effects of exogenous ACTH during oestrus on early embryo development and oviductal transport in the sow. AB - This study was conducted to assess the effects of ACTH injections on the early development of embryos and their transportation to the uterus. Fifteen sows were monitored for ovulation using transrectal ultrasonography during the first two oestrous periods after weaning. The sows were randomly divided into a control group (C group, n = 8) and an ACTH-treated group (ACTH group, n = 7), and were all surgically fitted with intra-jugular catheters. From the onset of the second standing oestrus after weaning, the sows were injected (NaCl/synthetic ACTH) every 4 h. Blood samples were collected immediately before and 45 min after each injection. All sows were inseminated once 10-33 h before ovulation in their second oestrus after weaning. At 48 (n = 4) or 60 (n = 11) h after ovulation during their second oestrus, the sows were killed and the embryos retrieved from the oviduct and uterus. The embryos were counted and compared with the number of corpora lutea, cleavage rate was noted and, finally, the embryos were prepared for confocal laser scanning microscopy and transmission electron microscopy. There was no difference between the groups regarding cleavage rate, the cytoskeleton, or the number of active nucleoli. However, the ACTH group had significantly (p < 0.05) fewer ova/embryos retrieved (51%) than the C group (81%), and there was a tendency towards faster transportation to the uterus in the ACTH group, possibly because of high progesterone concentrations during treatment. To conclude, administration of ACTH every 4 h from onset of oestrus to 48 h caused significant loss of oocytes or embryos, and possibly faster transportation through the oviduct. PMID- 17348968 TI - Total and differential leucocyte counts and lymphocyte subpopulations in lymph, afferent and efferent to the supramammary lymph node, during endotoxin-induced bovine mastitis. AB - Leucocyte trafficking in afferent and efferent mammary lymph and the supramammary lymph node in cows was examined during 4 h after intramammary infusion of endotoxin from Escherichia coli. Total and differential leucocyte counts were measured in milk, blood and lymph. The proportions of CD4(+), CD8(+), major histocompatibility complex (MHC) class II(+) and IgM(+) lymphocytes were examined in the lymph and lymph node. At post-infusion hour (PIH) 4, the flow rates of both lymph fluids had increased approximately eightfold. Total leucocyte concentration increased in afferent lymph, but decreased in efferent lymph. Neutrophils increased in afferent lymph at PIH 2 and in efferent lymph and milk at PIH 4. The predominant cell type in afferent lymph shifted from lymphocyte to neutrophil while lymphocyte was still at PIH 4 the predominant type in efferent lymph. Among the lymphocytes, B cells were predominant in afferent lymph and lymph node at PIH 4 while T cells, mainly CD4(+) cells, were predominant in efferent lymph both at PIH 0 and PIH 4. The CD4 : CD8 ratio was higher in efferent lymph and the challenged lymph node than in afferent lymph and the control node, respectively. There was a significant difference in proportions of each lymphocyte subpopulation except for IgM(+) cells, between afferent and efferent lymph after infusion. According to the results, there was already during the first hours of the immune response, a non-random trafficking of neutrophils and lymphocyte subpopulations resulting in a changed distribution of cells in afferent and efferent lymph and a difference in lymphocyte reactivity between the two lymph fluids. PMID- 17348970 TI - Effect of body weight, age and breeding history on canine sperm quality parameters measured by the Hamilton-Thorne analyser. AB - During the last decade, several computer assisted sperm analysis (CASA) systems have been validated for canine sperm quality assessment. Regarding the impressive possibilities of these systems, further research is required to determine which CASA measurements are of clinical importance in canine andrology. In the present study, the sperm quality parameters obtained by the Hamilton-Thorne Semen Analyser (Ceros 12.1; HTR) were correlated with the body weight and the age of the dogs. Moreover, the sperm quality parameters of dogs with a different breeding history were compared. The sperm-rich fraction was collected from 111 dogs of 50 different breeds, which were presented at our department. Immediately after collection, the concentration, the total sperm output (TSO) and 13 different sperm motility and velocity characteristics were measured by the HTR. The percentage of live spermatozoa and the spermatozoal morphology were examined on eosin/nigrosin stained smears. Based on their breeding history, the dogs were divided in three groups: 'fertile' (n = 60), 'subfertile' (n = 17) or 'not used for breeding' (n = 34). Significant (p < 0.05) correlations were established between the body weight of the dogs and the TSO (r = 0.245) and velocity curvilinear (VCL; r = -0.220), respectively. The age was negatively correlated with the percentage of normal spermatozoa (r = -0.203; p < 0.05). The correlations with all the other evaluated sperm parameters were low and not significant. Significant differences between the 'fertile' and the 'subfertile' group were found for all of the evaluated sperm quality parameters (except for BCF, LIN, STR and MEDIUM). In conclusion, dogs tend to produce ejaculates with a lower percentage of normal spermatozoa with increasing age and dogs with higher body weights produce ejaculates with a higher TSO and a lower VCL. Significantly poorer sperm characteristics were found for dogs with lower in vivo fertility results. PMID- 17348969 TI - Effect of repeated stress treatments during the follicular phase and early pregnancy on reproductive performance of gilts. AB - In pig husbandry, stress is being considered an important cause of impaired reproductive performance. Therefore, an experiment was performed to quantify effects of repeated stressors during the follicular phase and/or during early pregnancy on reproductive performance of gilts. Eighty-one cyclic gilts were assigned to one of four treatments, namely, stress treatment during the follicular phase (n = 20), stress treatment during early pregnancy (n = 20), stress treatment during both phases (n = 21) and no stress treatment (n = 20). All gilts were housed individually, but gilts in the stress treatments had no opportunity for visual or physical contact with other gilts. Further, animals in a stress-treatment were grouped for half an hour at the start of the treatment and during the treatment period nose-sling and an unpredictable feeding scheme were applied regularly. The extent of stress was monitored using heart rate measurements, behavioural observations and saliva cortisol levels during nose sling fixation. Of the 81 gilts, 93% showed oestrus and were inseminated. Of these, 93% were pregnant at day 35, having 17.9 +/- 0.3 ovulations and 15.6 +/- 0.3 foetuses. These parameters were not affected by treatment. The stress treatment during the follicular phase tended to shorten cycle length (stress: 20.8 +/- 0.20; control: 21.2 +/- 0.17 days, p = 0.07) and weight of foetuses at day 35 (stress: 4.47 +/- 0.08 g; no stress: 4.69 +/- 0.08 g, p = 0.06); stress during early pregnancy did not affect any of the reproduction parameters. Percentage stereotypic behaviour, heart rate and saliva cortisol levels varied greatly between animals and between days, but did not differ between the treatments. No relationships were found between any of the reproductive parameters and any of the stress parameters (heart rate, cortisol, stereotypic behaviour). These results indicate that the repeatedly applied acute stressors did not generate a chronic stress-response and that these stressors during the follicular phase and/or during early pregnancy did not affect reproductive processes. It is not clear how these findings relate to suggested effects of stress(ors) on reproductive performance in pig husbandry. PMID- 17348972 TI - Comparison of computer-assisted sperm motility analysis parameters in semen from Belgian blue and Holstein-Friesian bulls. AB - Subjective microscopic sperm motility results have recently been demonstrated to differ between Holstein-Friesian (HF) and Belgian Blue (BB) bulls. However, such assessments are rather imprecise. In the present study, sperm motility was assessed objectively by means of the Hamilton Thorne CEROS version 12.2c computer assisted sperm motility analyser (CASA), and differences between the BB and HF breed could also be demonstrated. Higher percentages of both totally (p < 0.0001) and progressively (p < 0.0001) motile spermatozoa were encountered in the HF breed compared with the BB breed. Furthermore, a lower kinetic efficiency of the BB spermatozoa, evidenced by a lower beat cross-frequency (p = 0.0007) combined with a higher lateral head displacement (p = 0.0015), was the basis for the lower velocity of BB sperm cells. Additionally, BB spermatozoa move less straight forward, resulting in a lower straightness (p < 0.0001). No sperm motility differences were observed between age groups within the BB breed. The breed differences were observed in the examined bull populations residing at AI centres, in Belgium for the BB bulls and in the Netherlands for the HF bulls. However, these bull populations are selected for fertility. A similar pattern was observed in an unselected bull population of both breeds, although these differences were mostly non-significant for the different CASA parameters. Nevertheless, these data suggest that a genetic component might be responsible for the observed sperm motility breed differences. PMID- 17348971 TI - Effect of sperm cryopreservation and supplementing semen doses with seminal plasma on the establishment of a sperm reservoir in gilts. AB - Frozen-thawed (FT) boar sperm have a reduced fertile life, due in part to a capacitation-like status induced by cooling. Reversal of this cryocapacitation in vitro by exposure to boar seminal plasma (SP) has been demonstrated. The objective of these studies was to determine the effect of SP on the ability of FT sperm to create an oviductal sperm reservoir following artificial insemination (AI). In Experiment one, 35 pre-pubertal gilts were injected (IM) with 400 IU eCG plus 200 IU hCG to induce oestrus. At detection of oestrus, gilts were inseminated with 3 x 10(9) live sperm, either fresh (FS; n = 13), FT (n = 10), or FT supplemented with 10% v/v SP (n = 12). Gilts were killed 8 h later, their reproductive tracts recovered and the uterotubal junctions (UTJs) flushed to recover sperm. Fewer (p < 0.01) sperm were recovered following FT, compared to FS, inseminations, and there was no evident effect of SP. In Experiment two, 30 pre-pubertal gilts received IM injections of 1000 IU eCG followed by 5 mg pLH 80 h later to control time of ovulation. Gilts were inseminated with 3 x 10(9) live FS sperm (n = 6), FT sperm (n = 15) or FT sperm plus 10% SP (n = 9) at 12 h before ovulation and then sacrificed 8 h later. The UTJs were dissected and flushed for sperm recovery. Fewest (p < 0.001) sperm were recovered following FT insemination and there was no evident effect of SP. These data demonstrate that the size of the sperm reservoir is markedly reduced in gilts inseminated with FT sperm. However, the lack of effect of SP suggested that either it did not reverse cryocapacitation or that such a reversal does not impact the in vivo ability to create a sperm reservoir. PMID- 17348973 TI - Effect of sperm cryopreservation on the European eel sperm viability and spermatozoa morphology. AB - The main objective of the present work was to study the effect of cryopreservation of European eel sperm both on the sperm viability and the spermatozoa head morphology. Spermatozoa morphology was evaluated with computer assisted morphology analysis after collection in fresh samples, after adding the freezing medium containing dimethyl sulfoxide as cryoprotectant and, finally, after the cryopreservation process and thawing. Cell viability was assessed, in both fresh and thawed samples, by Hoechst 33258 staining. Computer-assisted sperm analysis (CASA) was used to determine the percentage of motile cells and to measure motility parameters in sperm samples. A significant decrease of head perimeter (12.56%) and area (17.90%) was detected from spermatozoa in fresh to thawed samples, indicating that cells do not recover the original size after the cryopreservation process. CASA was used to measure the percentage of motile cells (51.9%) and spermatozoa motility parameters such as curvilinear, straight line and angular path velocities, as well as beating cross frequency. This technique was employed in the fresh sperm samples but proteins present at the freezing medium (L-alpha-phosphatidylcholine) made impossible to use this last technique in thawed samples. When sperm viability was assessed by Hoechst staining, a significant decrease of approximately 15% (73.10 vs 58.26%) of alive spermatozoa was registered from fresh to thawed samples. The percentage of motile cells measured by CASA in fresh samples (51.9%) was lower than the percentage of alive cells determined by Hoechst stainning, suggesting the existence of different batches of spermatozoa in different stages of development, even during the eight to tenth weeks of treatment, when the highest sperm quality was found. PMID- 17348974 TI - The embryonic pregnancy signal oestradiol influences gene expression at the level of translational initiation in porcine endometrial cells. AB - In the pig, conceptus-derived oestrogens (days 11 and 12 of pregnancy) seem to be a critical component of the signalling mechanism for maternal recognition of pregnancy. Embryonic oestrogens can mediate effects on endometrial function by interactions with epithelial and stromal oestrogen receptors (ER). Recent data demonstrate that cell membrane ER interacts with the phosphatidylinositol 3 kinase/Akt pathway in several types of cells. The protein kinase Akt is involved in the control of cell growth, survival and proliferation. One distinct function of the Akt signalling cascade is its ability to phosphorylate the eukaryotic initiation factor-4E (eIF-4E)-binding protein 1 (4E-BP1). This phosphorylation suppresses the inhibitory effect of 4E-BP1 on the translation initiation factor eIF4E and in such a way potentially stimulates gene expression at the level of translational initiation. The aim of the present study was to examine if embryonic oestradiol (E(2)) transmits its effect by such a mechanism. Endometrial cells of cyclic gilts (day 13 of the oestrous cycle, n = 4) were cultured and supplemented with vehicle (control), E(2) (50 and 100 pm/l) or with the selective ER modulator raloxifen (10 and 1000 nm/l), and incubated for 24 h. The cell viability was detected by MTT assay, the abundance and phosphorylation of Akt, 4E BP1 and ERalpha was analysed by Western blotting. Incubation with E(2) or raloxifen did not alter endometrial cell viability. The phosphorylation of Akt at Ser(473) seems to be increased by E(2) (p < 0.05) and decreased by raloxifen (p > 0.05). Raloxifen (1000 nm/l) induced a band shift in 4E-BP1 to the highest electrophoretic mobility which reflects a decrease in phosphorylation (p < 0.05), whereas an influence of E(2) on 4E-BP1 phosphorylation could not be detected. The decrease (p < 0.05) of the abundance of the 80 kDa ERalpha form both by E(2) and raloxifen indicates that the E(2)-stimulated Akt phosphorylation and the inhibition of 4E-BP1 phosphorylation by raloxifen is an E(2) ER-transmitted process. Therefore, embryonic oestrogens can potentially transmit their effect by influencing signalling cascades which modulate gene expression at the level of translational initiation. PMID- 17348975 TI - Effect of initial cumulus morphology on meiotic dynamic and status of mitochondria in horse oocytes during IVM. AB - The aim of this investigation was to examine the chromatin configuration of the nucleus, pattern of mitochondrial aggregation and mitochondrial activity in parallel studies in the same horse oocytes. Horse oocytes recovered by ultrasound guided follicle aspiration in vivo were classified according to two main initial cumulus morphologies as having compact or expanded cumulus. The percentage of oocytes with a diplotene meiotic configuration at the time of recovery from the follicles was highest in compact oocytes. Oocytes with expanded cumulus layers at the time of recovery matured more rapidly in vitro and reached a proportion >50% at the metaphase II stage (M 2) sooner during in vitro maturation (IVM), than did compact oocytes. The mitochondrial aggregation pattern changed from finely distributed (Type 1) through crystalline (Type 2) to an aggregated, granulated appearance (Type 3) during IVM. The pattern of mitochondrial aggregation at the time of recovery was associated with the initial cumulus morphology of the oocyte, in that compact oocytes had a higher proportion of Type 1 aggregation, whereas expanded oocytes had a higher proportion of Type 3. The fluorescence intensity of metabolic active mitochondria, measured by fluorescence intensity (Em 570) per oocyte after MitoTracker CMTM Ros orange labelling, increased in the oocytes during IVM and depended on initial cumulus investment. Oocytes with the granulated type of aggregated mitochondria Type 3 had the highest level of metabolic activity and were in more progressed stages of meiosis (A 1-M 2). Oocytes initially having expanded layers of cumulus reached significantly higher levels of mitochondrial activity after IVM than did oocytes initially having compact cumuli. During resumption of meiosis the mitochondrial activity of oocytes with initially expanded cumulus increased continuously up to M 2, whereas in oocytes from compact cumulus-oocyte complex (COC), the activity declined after A 1/T 1 stages of meiosis. PMID- 17348976 TI - Role of cumulus cells on in vitro maturation of canine oocytes. AB - The objectives of the present study were to investigate the relationship between the morphological status of cumulus cells surrounding canine oocytes after maturation culture and the meiotic stage of the oocytes. In addition, the effect of the removal of cumulus cells from canine cumulus-oocyte complexes (COCs) during maturation culture on their meiotic competence was examined. Canine COCs were collected from bitches at the anoestrous and dioestrous stages and only COCs with >110 microm in vitelline diameter were cultured in medium 199 with 10% canine serum for 72 h. In the first experiment, the relation between the morphological status of cumulus cells surrounding oocytes cultured for 72 h and their meiotic stages was examined. At the end of maturation culture, the proportions of intact, partially nude and completely nude oocytes were 65.2%, 22.9% and 11.9%, respectively. The proportion of maturation to metaphase II of completely nude oocytes was highest among the oocytes with different morphological status of cumulus cells. In the second experiment, the cumulus cells were partially or completely removed from COCs at 48 h after the start of maturation culture and the oocytes were cultured for a further 24 h. The proportion of oocytes reaching metaphase II in the completely denuded oocytes was significantly higher than that in the control oocytes without the removal treatment of cumulus cells. The results indicate that morphological status of cumulus cells surrounding oocytes may be related to the nuclear maturation of canine oocytes, and the removal of cumulus cells from COCs during maturation culture can promote the completion of oocyte meiotic maturation. PMID- 17348977 TI - Fluorescent stain method for the simultaneous determination of mitochondrial potential and integrity of plasma and acrosomal membranes in boar sperm. AB - The purpose of this study was to validate a technique for simultaneous evaluation of the plasma, acrosomal and mitochondrial membranes in boar spermatozoa, using an association of fluorescent probes: Propidium iodide (PI), fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) and JC-1. Three ejaculates from each of four different boars, all showing motility >or=80% and abnormal morphology 20 h after GnRH treatment. The levels of ANPT-2 mRNA decreased at 10 and 25 h after treatment compared with other periods. The ratio of ANPT-2/ANPT-1 (an index for destabilization of blood vessels) increased in the follicles at 3-5 h after GnRH treatment only. Both of Tie-1 and Tie-2 receptor expressions decreased in the follicles at 25 h after GnRH treatment. The results of the present study indicated that mRNA expressions of ANPT-1, ANPT-2 and their receptors changed in the bovine follicles during periovulatory period. These results suggest that angiopoietin-Tie system is associated with the initiation of vasculature of follicle that grows towards ovulation. PMID- 17348987 TI - Relaxing/straightening of Afro-ethnic hair: historical overview. AB - Afro-ethnic hair, when compared with naturally straight hair, presents some important variations such as differences in diameter in many points of the thread, ellipsoidal threads, and low trend of hydrating the scalp thus turning the hair drier, because the natural sebum distribution is irregular along the thread. This kind of hair may be straightened through both chemical and thermal methods. Straightening is a chemical process by which excessively curly hair is straightened in an irreversible way. Generally, the products used are formulated in a cosmetic emulsion with high pH. In this review, we present the historical development of hair straightening or relaxing through the evolution of the product categories. PMID- 17348988 TI - Treatment of facial reticular veins with dynamically cooled, variable spot-sized 1064 nm Nd:YAG laser. AB - BACKGROUND: Facial reticular veins are often seen on the temple and periorbital areas in patients with genetic predisposition or after facial cosmetic surgery. AIM: The purpose of this study was to evaluate the efficacy and safety of dynamically cooled, variable spot sized 1064 nm Nd:YAG laser in the treatment of facial reticular veins. PATIENTS/METHODS: This is a retrospective study. Twenty patients with facial reticular veins who underwent treatment with dynamically cooled, variable spot sized 1064 nm Nd:YAG laser were evaluated. Patients were followed up 1 month to 2 years after the procedure. RESULTS: Objective and subjective improvement scores after one or two treatments of dynamically cooled, variable spot sized 1064 nm Nd:YAG laser were nearly 100% when appropriate parameters were used. CONCLUSION: Dynamically cooled, variable spot sized 1064 nm Nd:YAG laser is a safe and effective treatment for facial reticular veins. Most patients responded to one treatment and experienced no significant side effects other than tolerable pain associated with the procedure. PMID- 17348989 TI - Dutasteride improves male pattern hair loss in a randomized study in identical twins. AB - OBJECTIVES: This study compared the efficacy of dutasteride vs. placebo in the treatment of male pattern hair loss (androgenetic alopecia) in 17 pairs of identical twin males with androgenetic alopecia over a 1-year period. METHODS: In this randomized, double-blind, placebo-controlled, single-center study, one twin from each identical twin pair received dutasteride 0.5 mg/day for 12 months while the other received placebo for 12 months. Hair growth was evaluated using standardized clinical photographs, hair counts, and patient self-assessment questionnaires. RESULT: Dutasteride significantly improved hair growth at 1-year compared to placebo based on the analysis of the investigator assessment and the patient self-assessment questionnaires. Sixteen of 17 sets of twins completed the study, of which 15 sets correctly predicted the use of dutasteride. Only one set could not determine the active drug from the placebo. CONCLUSION: Through the use of identical twins, this randomized trial provides evidence that dutasteride significantly reduces hair loss progression in men with male pattern hair loss. PMID- 17348990 TI - Effect of pre-treatment of almond oil on ultraviolet B-induced cutaneous photoaging in mice. AB - BACKGROUND: Ultraviolet (UV) radiation has been implicated in photoaging and various types of skin carcinomas. Although the human skin has evolved several defense mechanisms to survive the insults of actinic damage like keratinization, melanin pigmentation, etc., it is still subjected to the harmful effects of sunlight. AIMS: In this study, the role of almond oil in reducing the degradative changes induced in skin upon exposure to UV radiation was investigated. METHODS: Mice were divided in four groups of 20 animals. Group I was the control group. Group II was negative control, which received almond oil treatment alone. Group III was exposed to UV radiation only and Group IV received both UV treatment and almond oil treatment. Visible skin grading assessed the changes based on a rating scale, biochemical tests (glutathione estimation and lipid peroxidation), and histopathologic studies. RESULTS: Upon exposure of mice to UV radiation, it was found that pronounced visible skin changes were seen after 12 weeks of exposure. The results of the biochemical tests, glutathione estimation, and lipid peroxidation showed that almond oil reduced the effect of UV light-induced photoaging on the skin. Histopathologic studies also indicated a photoprotective effect of almond oil on the skin after UV exposure. CONCLUSIONS: It was concluded that topical almond oil is capable of preventing the structural damage caused by UV irradiation and it was also found useful in decelerating the photoaging process. PMID- 17348991 TI - Reduction in the appearance of facial hyperpigmentation by topical N-acetyl glucosamine. AB - Glucosamine has been reported to inhibit melanin production in melanocyte culture. It thus has a potential to reduce hyperpigmentation via topical use. Due to stability limitations of glucosamine, we chose to clinically evaluate the stable derivative N-acetyl glucosamine (NAG). Based on in vitro Franz cell testing, NAG is a good skin penetrant. In an 8-week, double-blind, placebo controlled, left-right randomized, split-face clinical test, topical 2% NAG reduced the appearance of facial hyperpigmentation. In a second clinical study involving the topical combination of 2% NAG with 4% niacinamide, an agent previously shown to be clinically active, the effect on hyperpigmentation was greater. Both of these agents are well tolerated by the skin. This high tolerance coupled with relative ease of formulation and stability in solution make NAG, especially in combination with niacinamide, a suitable cosmetic ingredient for use in skin care products dealing with issues of skin hyperpigmentation. PMID- 17348992 TI - Pincer nail: aesthetic concept in surgery. AB - Although pincer nail deformity (PND) treatment is time consuming independent of whether it is based on surgical or conservative procedures, long lasting beneficial results are found only after surgical intervention. Typically destruction of the lateral matrix horns either surgically or by phenol cauterization or even ablation of the matrix is performed. In the past these procedures mainly aimed at relief from pain; however, currently more patients ask for the preservation of the nail unit and a good cosmetic outcome. Today reconstructive results that meet the patient expectations are available. An adapted novel surgical method which will preserve the matrix horns while correcting the shape of the phalanx and preventing renewed adhesion of the nail bed to the phalanx is presented. Therefore the restoration of a normal width-to length ratio of the nail plate with a cosmetically appealing result becomes possible. Surgical steps in an affected right toenail are presented. PMID- 17348993 TI - Comparative benefit of two thermal spring waters after photodynamic therapy procedure. AB - INTRODUCTION: Photodynamic therapy (PDT) is commonly used to treat actinic keratoses, superficial cutaneous carcinoma, photodamage, and/or acne. The aim of this study was to compare the usefulness of Avene thermal spring water (ATSW), a low mineral content spring water, to a high mineral content spring water. We evaluated post-PDT clinical symptoms and findings when used as an adjunctive therapy in postprocedure skin care. METHODS: A double-blind monocentric comparative study was conducted on 25 patients suffering from either vulgaris acne or photodamage with or without actinic keratoses. The patients were treated with 5-aminolevulinic acid (5-ALA) activated with an intense pulsed light and/or blue light source. Patients were randomized so that 12 patients treated their faces with ATSW and 13 were treated with a comparative water spray. Clinical signs were evaluated by the investigator at day 0, before and 15 min after the first spraying, at days 2, 4, and 7, and each day from day 0 to day 6 by patients. Clinical signs (erythema, stinging, pruritus, pain, and tightening) were evaluated by the use of a 4-point grading scale. RESULTS: The intragroup analysis showed that pain was significantly reduced by ATSW spraying at days 2, 4, and 7. The evaluation by patients showed that only ATSW alleviates pain from day 3 to day 6. The between-group analysis revealed that pruritus was significantly reduced by ATSW at day 7. Erythema, stinging, and tightening were not significantly reduced by both waters. Patients wished to continue using ATSW in 83% of cases. CONCLUSION: This comparative clinical trial demonstrates that ATSW, a low mineral content spring water, can be useful after ALA-PDT in reducing postprocedure cutaneous inflammation and patient discomfort better than a high mineral content spring water. PMID- 17348994 TI - A comparison of triple combination cream and hydroquinone 4% cream for the treatment of moderate to severe facial melasma. AB - The aim of this study was to compare the efficacy and safety of a triple combination (TC) cream and monotherapy with hydroquinone (HQ) cream in the treatment of moderate to severe facial melasma. A total of 120 patients applied TC cream once daily or HQ cream twice daily for 8 weeks. Evaluations included static global severity assessment of melasma, improvement of melasma over time, local tolerability, and adverse events. TC cream was significantly more effective than HQ cream from week 4 onwards: lesions were approximately equivalent to the surrounding skin in 35% of all TC-treated patients, compared to 5% of those who used HQ cream (P = 0.0001). Improvement of more than 75% was achieved by 73% of TC cream patients and 49% of HQ cream patients (P = 0.007). The incidence of adverse events (erythema, burning sensation, and desquamation) was similar in both groups. No patient dropped out of the study because of drug-related adverse events. TC cream was more effective than the HQ cream for the treatment of moderate to severe facial melasma. Both products had similar safety profiles. PMID- 17348995 TI - Elderly skin and its rejuvenation: products and procedures for the aging skin. AB - In the last few decades, there has been a substantial increase in the population of people over 60 years of age. Most of them maintain a good general health and physical activity and fitness. For these individuals there is a good number of dermatologic procedures, medications, and cosmetics that can be prescribed to improve the aspect of skin aging, providing an improvement in their self-esteem and quality of life as a result of their better look. We will discuss the mechanisms of skin aging, and the procedures and substances used to minimize its deleterious effects, such as sunscreens, estrogens, chemical peels, toxin botulinum, fillers and surgical procedures, among others. The use of makeup and the adverse reactions to cosmetics will also be mentioned. PMID- 17348996 TI - Achieving good cosmetic results following pulsed dye laser therapy for port wine stains, a short report. PMID- 17348997 TI - Nail cosmetics in nail disorders. AB - The clinical features of nail dystrophies depend on the part of the nail that has been damaged. Due to the important functions of fingernails and toenails, any abnormality of the nail causes impaired function of the hand or foot. Moreover, the aesthetic aspect of the nail may affect employability, self-esteem, and interaction with other people. Because the nails are often difficult to treat, cosmetology may be an effective support to medical treatment. Nail cosmetics may help the patient to cope with his or her nail dystrophy while waiting for treatment to show its efficacy. It may also be the only choice to hide nail dystrophy where the nail is irreversibly damaged. Nail cosmetics may also function at treatment for onychtillomania, nail biting, and nail ingrowing. PMID- 17348998 TI - The use of hydroxy acids on the skin: characteristics of C8-lipohydroxy acid. AB - The hydroxy acids are widely used in skin creams because of their exfoliating and rejuvenating effect on photoaged skin. As a member of this family, the salicylic acid derivative known in the literature as 2-hydroxy-5-octanoyl benzoic acid or beta-lipohydroxy acid has also been proposed as an exfoliant and as a treatment of photoaged skin and acne. This article reviews the effects of the hydroxy acids and compares them to those of the salicylic acid derivative. We propose the name C(8)-lipohydroxy acid (C8-LHA) for this derivative to differentiate it from other related compounds. The lipophilic nature of C8-LHA and its relatively slow penetration in the skin afford it an exfoliating effect that is efficient at low concentrations. It appears to have antimicrobial, anti-inflammatory, and anticomedogenic properties, which make it effective against acne. Its antifungal and exfoliating properties are also likely to prove useful in combating dandruff. PMID- 17348999 TI - In praise of blushing. AB - Many people are extremely anxious about their blushing and regard it as the cause of their social difficulties rather than as a symptom of them. This paper addresses the belief that there is something inherently unpleasant or unattractive about blushing. Historical evidence shows that redness of the cheeks has long been regarded as a sign of facial beauty and youth, and transitory changes such as the blush have also been seen in a positive light as an indication of modesty and charm. The blush is an expression of shame and embarrassment and it too can be regarded in positive or negative light depending on the circumstances. What is distinctive about contemporary anxieties about blushing is that perceived personal inadequacies are in themselves reason to be ashamed and embarrassed: there is a vicious circle where a blush is both a sign of, and reason for, self-deprecation. This perception is not a necessary one but reflects current cultural values and this has implications for the treatment of blushing anxieties. PMID- 17349000 TI - The future of WFP programming in Sudan. PMID- 17349001 TI - Food aid and development in southern Sudan: implications of the Comprehensive Peace Agreement for response planning. AB - In the post-Comprehensive Peace Agreement (CPA) era a greater impact on the unacceptably high prevalence of child malnutrition is more likely to come from additional investment and attention to education, health, hygiene, sanitation and childcare practices than from expanded food aid interventions. The negligible impact of food aid on malnutrition, although most commonly challenged on the quality of needs assessments, is equally attributable to the timing of deliveries, and a dysfunctional distribution system. Comparatively few resources have been allocated to strengthen skills for assessing, analysing and understanding community priorities, local economies, and social safety nets. A more thoughtful allocation of scarce funds could have more impact if a range of alternative responses was considered. Participation in and commitment to a more independent livelihoods analytical forum would improve communication with the new government, local leaders and other partners, as well as providing a platform for reaching consensus on both humanitarian and development planning over the next five years. PMID- 17349002 TI - Sub-regional integration in Sudan: the key to food security and recovery. AB - The signing of the Comprehensive Peace Agreement (CPA) in Sudan has created a new opportunity for peace. Approaches to food security must now be reoriented based on the agro-ecological diversity in Sudan. WFP is in a unique position to catalyse an approach to food security that meets immediate needs and contributes to long-term recovery, in collaboration with the Government of National Unity (GNU) and the Government of South Sudan (GOSS). Aggregate food production in Sudan has increased in the past decade. At sub-regional levels, however, many areas remain food insecure. Major research must be undertaken to identify optimum levels of food production and barriers to access to food at sub-regional levels as a first step towards linking deficit areas with areas of surplus. Initiatives must also be undertaken to facilitate increased integration between sub-regions. Increased sub-regional linkages could ensure more efficient delivery of food in the short term as well as recovery and economic growth in the long term. PMID- 17349003 TI - Global factors shaping the future of food aid: the implications for WFP. AB - Food aid is a key component of a humanitarian response but its use in other programming contexts is subject to numerous criticisms. Even in humanitarian emergencies food aid is often late, unreliable and out of proportion to other elements of the response. Three major factors will shape the future of food aid. First, mechanisms of food aid governance are being reviewed and may undergo major changes--particularly the Food Aid Convention now that hopes have diminished for an Agreement on Agriculture at the World Trade Organisation. The second significant factor is donor agency trends. Overall levels of food aid have dropped fairly steadily in recent decades and there are several discernible trends in resource allocation, procurement and the use of food aid. The third factor is an emerging body of best practice that will define acceptable standards of food aid programming in the future. PMID- 17349004 TI - Looking beyond food aid to livelihoods, protection and partnerships: strategies for WFP in the Darfur states. AB - The humanitarian crisis in Darfur remains extremely serious. The optimism that followed the signing of the Abuja Peace Accord was followed by a rapid deterioration in security on the ground in part associated with increasing factionalism in various rebel movements. This paper briefly reviews the evolution of the crisis, its impact on lives and livelihoods and the response by the World Food Programme (WFP) to June 2006. The major challenges and issues facing the food aid programme in the previous 18 months included: dealing with insecurity while maintaining or even extending programme outreach; the need to link protection with assistance more explicitly; and determining the wider impact of food aid programming on the processes and institutions linked with the conflict. The paper discusses the main strategic issues facing WFP in the future such as: integrating security and protection with needs assessments and operational decisions, broadening response strategies beyond food aid and bringing livelihoods to the fore, the need to review cost-efficiency, promoting partnerships and strengthening national and regional capacities. PMID- 17349005 TI - Conflict, camps and coercion: the ongoing livelihoods crisis in Darfur. AB - This paper presents the findings of a study commissioned by World Food Programme (WFP) in early 2006 to enhance understanding of how the conflict in Darfur has affected livelihoods and markets, and of the effects of food aid. The livelihoods of many in Darfur were devastated early on in the conflict, principally through the widespread looting or destruction of assets and highly restricted population movements, which struck at the heart of pre-conflict livelihoods. Livelihood strategies for most people are now restricted, poorly remunerated and often associated with high risk of attack. Patterns of coercion and exploitation have also become entrenched; and markets and trade, the lifeblood of Da fur's economy pre-conflict, severely disrupted. Against this backdrop the impact of food aid on livelihoods in Darfur has been overwhelmingly positive. The paper proposes a number of preconditions for investment in recovery in Darfur, and recommends ways in which livelihoods can be supported in the current context of ongoing conflict. PMID- 17349006 TI - From food aid to livelihoods support: rethinking the role of WFP in eastern Sudan. AB - Despite more than 20 years of distribution of free emergency food in eastern Sudan (38 years in the case of refugees) Global Acute Malnutrition rates are currently the highest in the country. There has been no real improvement in the chronic livelihoods vulnerability that affects people in the region--particularly pastoralists. Food security must be seen from an informed livelihoods perspective. While food aid may still be required as part of transition, WFP must rethink its assistance strategy and advocate for complementarity in the efforts by development actors working across a range of sectors. Alternative models and interventions focused on the rehabilitation of markets and the development of' cargo nets' for the destitute, including cash transfers, must be developed and tested. Land tenure issues should be given particular attention. Food aid will probably remain an important element in the overall response, but its significance relative to other less developed forms of interventions should be reassessed. PMID- 17349007 TI - Conflict, trade and the medium-term future of food security in Sudan. AB - Recent economic growth and the Comprehensive Peace Agreement (CPA) have both been seen as grounds for optimism about the future of food security in Sudan. However, solving the North-South conflict (if indeed it is solved) does not resolve conflicts within either the North or the South and may even encourage a variety of conflicts. The classic neoliberal prescription of peace, growth and foreign investment may deepen (and obscure) the needs and grievances of those who have historically been left behind in a dysfunctional development process. Historically, some of those marginalised by patterns of development in Sudan have chosen to rebel, while others have had their grievances diverted against those even more marginal than themselves. Dysfunctional and violent processes of development must be reversed. They cannot be adequately compensated for--but may be legitimised--by attempts to use food aid as a 'safety net'. Meanwhile, those who benefited from war may have incentives to derail the peace. PMID- 17349008 TI - The future of food security in the Three Areas of Sudan. AB - Currently, the pace of recovery in the 'Three Areas' is moving faster than the implementation of the Comprehensive Peace Agreement (CPA). This gap is leading to greater imbalances in income, unsustainable urbanization, overexploitation of the environment and resource based conflict. Unless regulated, the likely result will be chronic poverty and an undermining of the success of the CPA. Agencies must be mindful of how they provide assistance so that they support the CPA. The analysis of food security should take place in the context of a larger political, social and economic analysis of the emerging situation. The least developed areas should be prioritised and interventions should provide benefits to the full range of socioeconomic groups. WFP must identify its role in the wider and integrated response. It should support the emerging peace process and the key reforms. If WFP chooses to consolidate its activities, it will require capable strategic partners. If it chooses to invest more in building the capacity of government and community structures, it must improve its skill base and field presence. PMID- 17349009 TI - Translational mini-review series on type 1 diabetes: Systematic analysis of T cell epitopes in autoimmune diabetes. AB - T cell epitopes represent the molecular code words through which the adaptive immune system communicates. In the context of a T cell-mediated autoimmune disease such as type 1 diabetes, CD4 and CD8 T cell recognition of islet autoantigenic epitopes is a key step in the autoimmune cascade. Epitope recognition takes place during the generation of tolerance, during its loss as the disease process is initiated, and during epitope spreading as islet cell damage is perpetuated. Epitope recognition is also a potentially critical element in therapeutic interventions such as antigen-specific immunotherapy. T cell epitope discovery, therefore, is an important component of type 1 diabetes research, in both human and murine models. With this in mind, in this review we present a comprehensive guide to epitopes that have been identified as T cell targets in autoimmune diabetes. Targets of both CD4 and CD8 T cells are listed for human type 1 diabetes, for humanized [human leucocyte antigen (HLA) transgenic] mouse models, and for the major spontaneous disease model, the non obese diabetic (NOD) mouse. Importantly, for each epitope we provide an analysis of the relative stringency with which it has been identified, including whether recognition is spontaneous or induced and whether there is evidence that the epitope is generated from the native protein by natural antigen processing. This analysis provides an important resource for investigating diabetes pathogenesis, for developing antigen-specific therapies, and for developing strategies for T cell monitoring during disease development and therapeutic intervention. PMID- 17349010 TI - Translational mini-review series on type 1 diabetes: Immune-based therapeutic approaches for type 1 diabetes. AB - Type 1 diabetes (T1D) is often considered the prototype organ-specific autoimmune disease in clinical immunology circles. The key disease features - precise destruction of a single endocrine cell type occurring on a distinct genetic and autoimmune background - have been unravelled in recent years to such an extent that there is a growing expectation that the disease should be curable. T1D is something of an orphan disease, currently managed by endocrinologists yet dependent upon the wit of immunologists, both basic and clinical, to find the best approaches to prevention and cure. Type 1 diabetes thus represents one of the most active arenas for translational research, as novel immune-based interventions find their way to the clinic. The first serious attempt at immune based treatment for T1D was in 1984, the first at prevention in 1993; current and planned trials will take us into the next decade before reporting their results. This paper represents the first attempt at a comprehensive review of this quarter century of endeavour, documenting all the strategies that have emerged into clinical studies. Importantly, the intense clinical activity has established robust infrastructures for future T1D trials and frameworks for their design. The evident success of the monoclonal anti-CD3 antibody trials in established T1D demonstrate that modulation of islet autoimmunity in humans after the onset of overt disease can be achieved, and give some reason to be cautiously optimistic for the ability of these and other agents, alone and in combination, to provide an effective immunotherapy for the disease. PMID- 17349011 TI - The levels of CD4+CD25+ regulatory T cells in paediatric patients with allergic rhinitis and bronchial asthma. AB - Our purpose was to determine whether numbers of CD4(+)CD25(+) T [T regulatory (T(reg))] cells and mRNA expression of functional molecules of T(reg) are related to airway allergy and disease severity in 51 paediatric patients with allergic rhinitis or bronchial asthma and 47 healthy controls. Surface markers were evaluated with flow cytometry, and mRNA was determined with real-time polymerase chain reaction. Children with allergic disease had fewer CD4(+)CD25(+) T cells (8 x 49% +/- 2 x 41% versus 9 x 58% +/- 2 x 43%, P<0 x 05) and CD4(+)CD25(hi) T cells (1 x 32% +/- 0 x 68% versus 1 x 70% +/- 0 x 68%, P<0 x 01) than control subjects. Numbers of CD4(+)CD25(+) and CD4(+)CD25(hi) T lymphocytes were higher in children with persistent allergic rhinitis and/or moderate-severe bronchial asthma than in those with respective milder disease. The number of T(reg) cells was correlated positively with total immunoglobulin E level. The mRNA expression of forkhead box P3 (FoxP3) was increased in moderate-severe versus mild asthma (2 x 93 +/- 0 x 38 versus 1 x 60 +/- 0 x 31, P< 0 x 01). Patients with moderate severe bronchial asthma also had increased mRNA expression of interleukin (IL)-10 compared with patients with mild asthma (15 x 24 +/- 4 x 07 versus 3 x 77 +/- 2 x 18, P<0 x 01). The suppressive function of T(reg) cells from patients with more severe asthma was competent in vitro. On average, decreased numbers of T(reg) cells in children with allergic airway disease might represent a defect of the T(reg) population. With increased expression of FoxP3 and IL-10 in T(reg) from patients with relatively severe allergic disease, adaptive and functional T(reg) might be generated in response to aggravated atopy and disease severity. PMID- 17349012 TI - Circulating mononuclear cells from euthyroid patients with thyroid-associated ophthalmopathy exhibit characteristic phenotypes. AB - Thyroid-associated ophthalmopathy (TAO) is a common yet poorly understood component of Graves' disease involving inflammation, congestion and soft tissue remodelling of the orbit. Unlike most autoimmune disorders, TAO has variable severity but follows a predictable course and is usually self-limited. The objective of this study was to investigate the phenotypic profile of peripheral blood mononuclear cells in euthyroid patients with TAO. The study was a prospective, consecutive analysis of the peripheral blood mononuclear cell phenotype in patients with TAO and normal controls. We demonstrate that the fraction of T cells expressing CD69, CD25 or CXCR4 is significantly greater in patients with TAO compared to control donors. In addition, the fraction of CD19(+) CD25(+) B cells is significantly greater. We did not find differences between the two groups of subjects in monocytes expressing these markers. There is a phenotypic shift in peripheral blood lymphocytes associated with TAO that appears durable and persists beyond the hyperthyroid phase of Graves' disease. These changes may support the immune reaction provoking orbital disease development. PMID- 17349013 TI - Indoleamine 2,3-dioxygenase enzyme activity correlates with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study. AB - Indoleamine 2,3 dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, suppresses T cell activity and is up-regulated by various inflammatory stimuli. The ratio of kynurenine, the main metabolite of tryptophan, to tryptophan (kyn/trp) reflects IDO activity. We calculated IDO activity and measured carotid intima-media thickness (IMT), a presymptomatic predictor of atherosclerosis, in 986 young adults (544 female, 442 male) for whom data on levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, high sensitive C-reactive protein (CRP), body mass index (BMI), waist circumference, waist-to-hip ratio, systolic and diastolic blood pressure and smoking habits were available. IDO activity correlated significantly with IMT in female subjects, but not in males. In a multivariate linear regression model, IDO did not correlate independently with IMT in female subjects. However, IDO activity correlated significantly with several risk factors for atherosclerosis in females, i.e. with age, LDL-C, BMI, weakly with CRP and inversely with HDL-C and triglyceride. In males IDO activity correlated significantly with CRP and inversely with HDL-C. In conclusion, our results suggest that the IDO enzyme is involved in the immune regulation of early atherosclerosis, particularly in young female adults, and could constitute a novel marker of immune activation in early atherosclerosis in females. PMID- 17349014 TI - Human ovarian tumour-derived chaperone-rich cell lysate (CRCL) elicits T cell responses in vitro. AB - Tumour-derived chaperone-rich cell lysate (CRCL), which is made up of numerous heat shock proteins, has been used successfully to generate tumour-specific T cell responses and protective immunity against a wide range of murine tumours. In this study, we have investigated the potency of human ovarian cancer-derived CRCL to activate dendritic cells (DC) and to generate tumour-specific T cells in vitro. CRCL was generated from primary ovarian cancers and SKOV3-A2, a HER2/neu, Wilm's tumour gene 1 (WT1) and human leucocyte antigen (HLA)-A2 positive human ovarian tumour cell line. Peripheral blood mononuclear cells from both HLA-A2(+) healthy donors and HLA-A2(+) ovarian cancer patients were stimulated weekly with autologous DC loaded with ovarian tumour-derived CRCL. After four to six stimulations in vitro, specific cytokine secretion and cytotoxicity were measured. CRCL promoted interleukin (IL)-12 secretion and enhanced the immunostimulatory capacity of DC. T cells from healthy controls and from ovarian cancer patients secreted higher amounts of interferon-gamma following in vitro restimulation with ovarian cancer-derived CRCL than with HER2/neu or WT1 peptide pulsed DC. We were also able to generate cytotoxic T lymphocyte activity against cancer-specific antigens such as HER2/neu and WT1 from all healthy donors, but from only one of the four ovarian cancer patients with bulky disease. These preliminary results substantiate further the concept that CRCL may prove to be a potent adjuvant for women suffering from ovarian cancer and that this personalized vaccine may be a promising approach for active immunotherapy. PMID- 17349015 TI - Oral and systemic administration of beta-glucan protects against lipopolysaccharide-induced shock and organ injury in rats. AB - beta-Glucans are glucose polymers with a variety of stimulatory effects on the immune system. The objective of this study was to determine the effect of prophylactic oral administration of soluble Saccharomyces cerevisiae-derived beta 1,3/1,6-glucan (SBG) on the outcome of experimental endotoxaemia and shock associated organ injury. Male Wistar rats were pretreated with SBG orally (SBGpo, 20 mg/kg/day) for 14 days, subcutaneously (SBGsc, 2 mg/kg/day) for 3 days, or vehicle (placebo). Rats were anaesthetized and subjected to endotoxaemia by intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (6 mg/kg) or saline infusion (sham). We observed significant levels of plasma beta-glucan in the SBGpo group (P<0 x 5), although the SBGsc group had levels approximately 40 fold higher despite a 10-fold lower dose. SBG prophylaxis caused enhanced blood pressure recovery following LPS-induced blood pressure collapse. Oral treatment with SBG attenuated the LPS-induced rise in plasma creatinine levels (P<0 x 05), indicating protection against renal injury. SBG also attenuated the plasma levels of aspartate aminotransferase and alanine aminotransferase (SBGpo, P<0 x 01; SBGsc, P<0 x 01), indicating protection against LPS-induced hepatic injury. A moderate increase in baseline interleukin (IL)-1beta levels was observed in the SBGsc group (P< 0 x 05). In the LPS-challenged rats, plasma levels of proinflammatory cytokines was moderately reduced in both SBG-treated groups compared to placebo. SBG treatment, particularly oral administration, had a striking effect on the haemodynamics of LPS-treated rats, although only a minute fraction of the orally administered beta-glucan translocated to the circulation. Enhanced organ perfusion may thus be responsible for the attenuated levels of indicators of kidney and liver injury seen in SBG-treated rats. PMID- 17349016 TI - Vasoactive intestinal polypeptide enhances oral tolerance by regulating both cellular and humoral immune responses. AB - Vasoactive intestinal polypeptide (VIP) is an important signal molecule of the neuroendocrine-immune network. In the immune system, VIP has been found to act as an endogenous anti-inflammatory mediator. In the current study, it was found that VIP administration regulated oral tolerance by inhibiting both cellular and humoral responses. Compared with vehicle-treated mice, mice treated with VIP during the development of ovalbumin (OVA)-induced oral tolerance exhibited the least delayed-type hypersensitivity (DTH), showed profoundly reduced proliferative capacity and produced less interferon (IFN)-gamma, interleukin (IL) 6, IL-5, IL-10 and interferon-inducible protein (IP-10). IgA-secreting cells in the gut as well as OVA-specific IgG and other isotypes levels in plasma were inhibited significantly after VIP-treatment. The VPAC2 receptor may be involved in VIP-mediated oral tolerance enhancement. Taken together, these results suggest that VIP enhanced oral tolerance via regulating both cellular and humoral responses. PMID- 17349018 TI - Melatonin induces neuritogenesis at early stages in N1E-115 cells through actin rearrangements via activation of protein kinase C and Rho-associated kinase. AB - Melatonin increases neurite formation in N1E-115 cells through microtubule enlargement elicited by calmodulin antagonism and vimentin intermediate filament reorganization caused by protein kinase C (PKC) activation. Microfilament rearrangement is also a necessary process in growth cone formation during neurite outgrowth. In this work, we studied the effect of melatonin on microfilament rearrangements present at early stages of neurite formation and the possible participation of PKC and the Rho-associated kinase (ROCK), which is a downstream kinase in the PKC signaling pathway. The results showed that 1 nm melatonin increased both the number of cells with filopodia and with long neurites. Similar results were obtained with the PKC activator phorbol 12-myristate 13-acetate (PMA). Both melatonin and PMA increased the quantity of filamentous actin. In contrast, the PKC inhibitor bisindolylmaleimide abolished microfilament organization elicited by either melatonin or PMA, while the Rho inhibitor C3, or the ROCK inhibitor Y27632, abolished the bipolar neurite morphology of N1E-115 cells. Instead, these inhibitors prompted neurite ramification. ROCK activity measured in whole cell extracts and in N1E-115 cells was increased in the presence of melatonin and PMA. The results indicate that melatonin increases the number of cells with immature neurites and suggest that these neurites can be susceptible to differentiation by incoming extracellular signals. Data also indicate that PKC and ROCK are involved at initial stages of neurite formation in the mechanism by which melatonin recruits cells for later differentiation. PMID- 17349019 TI - Melatonin prevents oxidative stress and changes in antioxidant enzyme expression and activity in the liver of aging rats. AB - This study compared the effects of melatonin supplementation on markers of oxidative stress, and on the activity and expression of antioxidant enzymes in the liver of young (3-month-old) and aging (24-month-old) rats. Animals were supplemented with melatonin in the drinking water (20 mg/L) for 4 wk. Liver concentration of thiobarbituric-reactive substances (TBARS), as an index of lipid peroxidation, and the oxidized to reduced glutathione ratio significantly increased in aged rats (+58%), while values did not significantly differ from the young in aged animals receiving melatonin. Significant decreases in the liver activities of Cu,Zn-superoxide dismutase (SOD) (-25%), cytosolic (-21%) and mitochondrial (-40%) glutathione peroxidase (GPx), and catalase (CAT) (-34%) were found in aged rats. Melatonin abolished these changes and also prevented the reduction of Cu,Zn-SOD (-33%), cytosolic GPx (-30%), and mitochondrial GPx (-47%) liver protein content as measured by Western blot. Reductions in Cu,Zn-SOD mRNA ( 39%), and GPx mRNA (-86%) levels induced by aging were also abolished by melatonin. In summary, our data indicate that melatonin treatment abrogates oxidative stress in the liver of aged rats, and that prevention of the decreased activity of CAT and the downregulation of Cu,Zn-SOD and GPx gene expression contribute to this effect. PMID- 17349020 TI - Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo. AB - Melatonin is known to regulate a variety of physiological processes including control of circadian rhythms, regulation of seasonal reproductive function, regulation of body temperature, and so forth. Accumulating evidence from in vitro and in vivo experiments using rodent and chicken has also suggested that melatonin may have an influence on skeletal growth and bone formation. However, little is known about the effects of melatonin on human osteoblasts, which thus remains to be elucidated. This study was performed to determine whether melatonin could affect the proliferation and differentiation of human osteoblasts in vitro and to demonstrate the possibility that melatonin could be applied as a pharmaceutical agent to shorten the treatment period of bone fracture, various osteotomies, and bone distraction. Reverse transcription-polymerase chain reaction and Western blot analysis showed that human osteoblasts expressed melatonin 1a receptor and that its expression levels decreased gradually with the age of the hosts. Melatonin stimulated the proliferation and alkaline phosphatase activity of human osteoblasts in a dose-dependent manner at the pharmacological concentrations. Melatonin also promotes gene expression of type I collagen, osteopontin, bone sialoprotein, and osteocalcin in a dose-dependent manner, and stimulated the mineralized matrix formation in vitro. Moreover, intraperitoneal administration of melatonin to mice increased the volume of newly formed cortical bone of femora. These results demonstrated that melatonin directly accelerated the differentiation of osteoblasts of human as well as rodent and chicken and also suggested that melatonin could be applied as a pharmaceutical agent to promote bone regeneration. PMID- 17349021 TI - Evidence for melatonin synthesis in the rat brain during development. AB - Melatonin production is not restricted to the pineal gland. Several extrapineal sources of this indole such as retina, Harderian gland, and immune system are well documented. Melatonin of pineal origin is not present in the rat at early stages of development. To assess the potential capacity of local melatonin synthesis by the immature brain and to gain insight into the relationship between melatonin production by the brain (without the pineal gland) and pineal gland during rat development, the melatonin content as well as the expression and activity of the melatonin-synthesizing enzymes, N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), were studied at fetal and postnatal stages. Moreover, melatonin-membrane receptor (MT(1)) expression was also analyzed. Both, the expression and activity of NAT and HIOMT were found in the brain with significant day/night differences in enzymes activities. Additionally, melatonin content was detected in all stages showing day/night differences depending on the stage of development. The brain nocturnal melatonin content was higher than diurnal content on postnatal day 16 and in adult rats which is in accordance with the pineal melatonin synthesis. To investigate the origin of this brain melatonin, pinealectomized rats were used and we found that the developing brain produced its own melatonin. Also, MT(1) expression was detected in brain during development. These results demonstrate that, when the pineal is not yet producing melatonin, there is melatonin synthesis by the brain that could be used as protection from free radical damage and/or could exert some actions through MT(1) receptors. PMID- 17349022 TI - Melatonin protects against rotenone-induced oxidative stress in a hemiparkinsonian rat model. AB - In the present study, we evaluated the effect of melatonin, a well-known free radical scavenger and neuroprotector, against rotenone-induced oxidative stress in a hemiparkinsonian rat model. The effect of melatonin on glutathione (GSH) depletion caused by unilateral, intranigral infusion of rotenone was investigated employing a spectrofluorimetric procedure. We also studied the effect of melatonin on rotenone-induced changes in the antioxidant enzymes superoxide dismutase (SOD) and catalase in the cytosolic fractions of substantia nigra (SN), employing spectrophotometric procedures. Rotenone-induced hydroxyl radicals (*OH) in the isolated mitochondria, as measured employing a sensitive HPLC electrochemical method, were significantly scavenged by melatonin. Melatonin treatment restored the rotenone-induced decrease in GSH level and changes in antioxidant enzyme (SOD and catalase) activities in the SN. Our results strongly indicate melatonin's beneficial use in Parkinson's disease therapy as an antioxidant. PMID- 17349024 TI - N1-acetyl-N2-formyl-5-methoxykynuramine modulates the cell cycle of malaria parasites. AB - We previously reported that intraerythrocytic malaria parasites have their development synchronized by melatonin and other products of tryptophan catabolism (i.e. serotonin, N-acetylserotonin and tryptamine). Here, we show that N(1) acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), a product of melatonin degradation, synchronizes Plasmodium chabaudi and Plasmodium falciparum. The synchronization is abrogated with a melatonin receptor antagonist, luzindole. We established quantitatively that a differential AFMK production occurred within the intraerythrocytic stages of rodent malaria parasite Plasmodium chabaudi (ring, trophozoite and schizont), when the infected erythrocytes were previously incubated with melatonin. Measurement of AFMK formation in P. chabaudi after incubation with melatonin at a concentration of 500 nmol/L revealed the following values for AFMK production: ring 0.1 +/- 0.1 nmol/L, trophozoite 22.9 +/- 0.5 nmol/L, schizont 29 +/- 5 nmol/L. Confocal and spectrofluorophotometer experiments with isolated parasites and infected-RBC, loaded with calcium indicator Fluo-4 showed that AFMK elicits an increase in the cytosol calcium concentration in these parasites. Our data suggest that AFMK could have an important role in modulating the cell cycle of malaria parasites mainly in the late stages (trophozoite and schizont). PMID- 17349023 TI - The effect of myocardial infarction on the synthesis, concentration and receptor expression of endogenous melatonin. AB - We examined the time course of changes in the synthesis and levels of endogenous melatonin and in the expression of MT(1) and MT(2) melatonin receptors 1 day, 2 and 4 wk after myocardial infarction (MI) in rats. MI was produced by ligation of the left anterior descending coronary artery. Transthoracic echocardiography was performed to characterize structural and functional changes after MI. mRNA levels were measured by real-time quantitative reverse transcription-polymerase chain reaction and proteins by Western blotting. One day after infarction, MI rats had 4.3 times (P < 0.001) higher pineal melatonin synthesis, than sham-operated animals, which was associated with the increased concentration of melatonin in plasma (P < 0.001) and left ventricle (LV) (P = 0.01). The amount of MT(1) receptor protein decreased significantly in MI LVs compared with control LVs 1 day after infarction (P < 0.01), followed by recovery during the next 2 wk. Furthermore, the expression of MT(1) receptor mRNA of the MI LVs was elevated 2 wk after infarction (P < 0.01) compared with control LVs. The amount of MT(2) receptor proteins in MI LVs was higher than in sham-operated LVs 1 day (P < 0.05) and 4 wk (P < 0.01) after MI. In conclusion, melatonin synthesis in the pineal gland increased rapidly in response to the MI, supporting an important role for endogenous melatonin in protecting the heart after MI. The observed changes in the expression of MT(1) and MT(2) receptors suggest that melatonin receptors may be involved in mediating, at least, in part, the protective effects of melatonin in the heart after infarction. PMID- 17349025 TI - Effect of melatonin on cholesterol absorption in rats. AB - This study evaluated the influence of melatonin on cholesterol absorption in rats fed on high cholesterol diet (HCD). HCD induced a remarkable increase in hepatic and plasma total cholesterol, plasma very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, a decrease in high density lipoprotein (HDL) cholesterol and an elevation in triacylglyceride (TG) levels in plasma and in the liver. Melatonin suspension (10 mg/kg), specially prepared for this purpose, cholestyramine (230 mg/kg) and ezetimibe (145 microg/kg) were administered orally to the rats fed HCD for 30 days. Melatonin significantly reduced cholesterol absorption in rats fed on HCD and caused significant decreases in total cholesterol, TG, VLDL- and LDL-cholesterol in the plasma and contents of cholesterol and TG in the liver. The level of HDL cholesterol was significantly increased after melatonin. These results suggested that inhibition of cholesterol absorption caused by melatonin could be a mechanism contributing to the positive changes in plasma cholesterol, lipoprotein profile and the lipid contents in the liver. PMID- 17349026 TI - Chronic melatonin treatment reduces the age-dependent inflammatory process in senescence-accelerated mice. AB - It is hypothesized that, besides increased free radical production, aging is a process also related to inflammation. Thus, female and male senescence accelerated (SAMP8) and senescence-resistant (SAMR1) mice of 5 and 10 months of age were studied to assess this hypothesis. Plasma from these mice was processed to determine nitric oxide (NO), and pro-inflammatory [interleukin (IL)-1beta, IL 2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and granulocyte macrophage colony-stimulating factor] and anti-inflammatory (IL-4, IL-5 and IL 10) cytokines. The results show the presence of an age-dependent increase in IFN gamma and TNF-alpha and a reduction in IL-2 levels, with minor changes in the remaining cytokines. Moreover, age was associated with a significant increase in NO levels. Chronic melatonin administration between 1 and 10 months of age counteracted the age-dependent production of pro-inflammatory cytokines and NO, reducing them to the levels found at 5 months of age. Melatonin also reduced the levels of the anti-inflammatory cytokines. The results of this study suggest the existence of an inflammatory process during aging and further support that melatonin behaves as an essential molecule against aging, for its anti inflammatory properties together with its antioxidative role reported elsewhere. PMID- 17349027 TI - Looking for the keys to diurnality downstream from the circadian clock: role of melatonin in a dual-phasing rodent, Octodon degus. AB - Melatonin is an essential component for circadian system function, whose daily plasma secretory rhythm is driven by the suprachiasmatic nucleus (SCN), contributing to the communication of temporal messages from the central circadian clock to all cells. Melatonin secretion peaks in the dark, regardless of whether animals are diurnal or nocturnal. To date, the precise mechanisms that explain how the circadian system is configured as nocturnal or diurnal remain unknown. The present study examines mid-day and midnight melatonin plasma levels and the influence of exogenous melatonin on the circadian system phasing of Octodon degus, a diurnal rodent, which exhibits nocturnal and diurnal chronotypes when free access to a wheel is provided. Plasma levels of melatonin were determined by RIA in blood samples taken from the jugular vein at mid-light (ML) and mid-dark (MD). Melatonin (0.5 mg/kg b.wt.) was orally administered in their drinking water for 30 days, 2 hr before the onset of darkness. The results showed that plasma melatonin levels and their qualitative effects, hypothermia and improved synchronization with no modification in the 24-hr wheel running activity (WR), were similar in both nocturnal and diurnal degus. Furthermore, melatonin can be used to improve the impaired circadian rhythmicity observed in aged animals, with no rebound effect after ceasing the treatment. It is concluded that plasma melatonin levels and the differential responses to melatonin do not seem to be responsible for nocturnal and diurnal chronotypes, and thus other mechanisms upstream, within, or downstream from the SCN should be investigated. PMID- 17349028 TI - The effect of pH on horseradish peroxidase-catalyzed oxidation of melatonin: production of N1-acetyl-N2-5-methoxykynuramine versus radical-mediated degradation. AB - There is a growing body of evidence that melatonin and its oxidation product, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), have anti-inflammatory properties. From a nutritional point of view, the discovery of melatonin in plant tissues emphasizes the importance of its relationship with plant peroxidases. Here we found that the pH of the reaction mixture has a profound influence in the reaction rate and products distribution when melatonin is oxidized by the plant enzyme horseradish peroxidase. At pH 5.5, 1 mm of melatonin was almost completely oxidized within 2 min, whereas only about 3% was consumed at pH 7.4. However, the relative yield of AFMK was higher in physiological pH. Radical-mediated oxidation products, including 2-hydroxymelatonin, a dimer of 2-hydroxymelatonin and O demethylated dimer of melatonin account for the fast consumption of melatonin at pH 5.5. The higher production of AFMK at pH 7.4 was explained by the involvement of compound III of peroxidases as evidenced by spectral studies. On the other hand, the fast oxidative degradation at pH 5.5 was explained by the classic peroxidase cycle. PMID- 17349029 TI - Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats. AB - We have previously shown that exogenous melatonin improves the preservation of the blood-brain barrier (BBB) and neurovascular unit following cerebral ischemia reperfusion. Recent evidence indicates that postischemic microglial activation exaggerates the damage to the BBB. Herein, we explored whether melatonin mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Melatonin (5 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, melatonin-treated animals did not have significantly changed systemic cellular inflammatory responses in the bloodstream (P > 0.05). Melatonin, however, significantly decreased the cellular inflammatory response by 41% (P < 0.001) in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45 positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45 positive) by 51% (P < 0.01) and 66% (P < 0.01), respectively, but did not significantly alter the population composition of T lymphocyte (CD3-positive/CD45 positive; P > 0.05). This melatonin-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction and improved neurobehavioral outcome by 43% (P < 0.001) and 50% (P < 0.001), respectively. Thus, intravenous administration of melatonin upon reperfusion effectively decreased the emigration of circulatory neutrophils and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia-reperfusion. The finding demonstrates melatonin's inhibitory ability against the cellular inflammatory response after cerebral ischemia-reperfusion, and further supports its pleuripotent neuroprotective actions suited either as a monotherapy or an add-on to the thrombolytic therapy for ischemic stroke patients. PMID- 17349030 TI - Melatonin and its synthesizing enzymes (arylalkylamine N-acetyltransferase-like and hydroxyindole-O-methyltransferase) in avian eggs and early embryos. AB - The presence of melatonin and the enzymes (transcripts and activities) involved in its synthesis, i.e. arylalkylamine N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), was investigated in the eggs and early embryos of Japanese quail at Hamburger-Hamilton stages 1-10. Melatonin was present in the egg yolk (approximately 70 pg/g) and albumen (approximately 20 pg/g). The average content of melatonin was approximately 416 pg/egg. AA-NAT and HIOMT transcripts were present in the oocytes, blastoderms, and ovarian follicles. AA-NAT-like and HIOMT activities were detected in quail egg yolk. The activity of AA-NAT in yolk was comparable with that found in the pineal gland when calculated per milligram of yolk or pineal gland, but was significantly lower when re-calculated per milligram of protein in the yolk or pineal gland. AA NAT-like activity was also identified in the ovarian follicles. Low HIOMT activity was detected in yolk, but not in the ovarian follicle. Both enzymes were essentially absent from early embryos although some residual activities, probably of yolk origin, were present in the stage 1 embryo. Melatonin and all the constituents needed for its synthesis (serotonin, AA-NAT and HIOMT activities) are contained within the avian yolk and could be used by the embryo from the very beginning of its development. The role of extrapineal melatonin in early avian development may be in protecting the embryo from the action of free radicals formed during intensive embryonic metabolism and/or it may participate (together with serotonin) in a 'diffuse neuroendocrine system' acting at early developmental stages, before differentiation of the nervous system. PMID- 17349031 TI - Doppler findings in a rare coronary artery fistula. AB - One of the primary forms of congenital anomalies of the coronary arteries is coronary artery fistula (CAF). It is defined as a direct communication between the coronary artery and any surrounding cardiac chamber or vascular structure, which bypasses the myocardial capillary bed. We present a newborn baby with a large coronary artery fistula connecting the left anterior descending (LAD) artery to the left ventricular (LV) apex. Associated cardiac abnormalities were found: a ventricular septal defect (diameter 4 mm), a patent foramen ovale as well as trivial tricuspid and mitral regurgitation. Here we demonstrate the echocardiograms of an extremely rare form of CAF diagnosed within the first days of postnatal life. PMID- 17349032 TI - The MAP kinase HwHog1 from the halophilic black yeast Hortaea werneckii: coping with stresses in solar salterns. AB - BACKGROUND: Hortaea werneckii is one of the most salt-tolerant species among microorganisms. It has been isolated from hypersaline waters of salterns as one of the predominant species of a group of halophilic and halotolerant melanized yeast-like fungi, arbitrarily named as "black yeasts". It has previously been shown that H. werneckii has distinct mechanisms of adaptation to high salinity environments that are not seen in salt-sensitive and only moderately salt tolerant fungi. In H. werneckii, the HOG pathway is important for sensing the changes in environmental osmolarity, as demonstrated by identification of three main pathway components: the mitogen-activated protein kinase (MAPK) HwHog1, the MAPK kinase HwPbs2, and the putative histidine kinase osmosensor HwHhk7. RESULTS: In this study, we show that the expression of HwHOG1 in salt-adapted cells depends on the environmental salinity and that HwHOG1 transcription responds rapidly but reciprocally to the acute hyper-saline or hypo-saline stress. Molecular modelling of HwHog1 reveals an overall structural homology with other MAPKs. HwHog1 complements the function of ScHog1 in the Saccharomyces cerevisiae multistress response. We also show that hyper-osmolar, oxidative and high temperature stresses activate the HwHog1 kinase, although under high-temperature stress the signal is not transmitted via the MAPK kinase Pbs2. Identification of HOG1-like genes from other halotolerant fungi isolated from solar salterns demonstrates a high degree of similarity and excellent phylogenetic clustering with orthologues of fungal origin. CONCLUSION: The HOG signalling pathway has an important role in sensing and responding to hyper-osmolar, oxidative and high temperature stresses in the halophilic fungi H. werneckii. These findings are an important advance in our understanding of the HOG pathway response to stress in H. werneckii, a proposed model organism for studying the salt tolerance of halophilic and halotolerant eukaryotes. PMID- 17349033 TI - Obesity and smoking are factors associated with poor prognosis in patients with bacteraemia. AB - BACKGROUND: Bacteraemia is still a major cause of case fatality in all age groups. Our aim was to identify the major underlying conditions constituting risk factors for case fatality in bacteraemia patients. METHODS: The study involved 149 patients (79 male and 70 female) with bacteraemia caused by Staphylococcus aureus (S. aureus) (41 patients), Streptococcus pneumoniae (Str. pneumoniae) (42 patients), beta-hemolytic streptococcae (beta-hml str.) (23 patients) and Eschericia coli (E. coli) (43 patients). Underlying diseases, alcohol and tobacco consumption and body mass index (BMI) were registered. Laboratory findings and clinical data were registered on admission and 6 consecutive days and on day 10 14. Case fatality was studied within 30 days after positive blood culture. Associations between underlying conditions and case fatality were studied in univariate analysis and in a multivariate model. RESULTS: Nineteen patients (12.8%) died of bacteraemia. We found obesity (p = 0.002, RR 9.8; 95% CI 2.3 to 41.3), smoking (p < 0.001, RR 16.9; 95% CI 2.1 to 133.5), alcohol abuse (p = 0.008, RR 3.9; 95% CI 1.3 to 11.28), COPD (p = 0.01, RR 8.4; 95% CI 1.9 to 37.1) and rheumatoid arthritis (p = 0.045, RR 5.9; 95% CI 1.2 to 28.8) to be significantly associated with case fatality in bacteraemia in univariate model. The median BMI was significantly higher among those who died compared to survivors (33 vs. 26, p = 0.003). Obesity and smoking also remained independent risk factors for case fatality when their effect was studied together in a multivariate model adjusted with the effect of alcohol abuse, age (continuos variable), sex and causative organism. CONCLUSION: Our results indicate that obesity and smoking are prominent risk factors for case fatality in bacteraemic patients. Identification of risk factors underlying fatal outcome in bacteraemia may allow targeting of preventive efforts to individuals likely to derive greatest potential benefit. PMID- 17349034 TI - What motivates British parents to consent for research? A questionnaire study. AB - BACKGROUND: Informed consent is the backbone of a clinical trial. In children this is given by their parents. There have been many studies in the neonatal population but little is known about the views of the parents of infants and young children from within the United Kingdom. The objectives of this study were to assess what motivates parents to consent to a randomised clinical trial (RCT), their feelings on consent and participation and the factors that would influence their decision to take part in a future study. METHODS: The setting was a multi centre randomised but non-blinded equivalence trial of oral versus intravenous (IV) treatment for community acquired pneumonia in previously well children aged 6 months to 16 years in the UK (PIVOT Study). Parents were sent a postal questionnaire at the end of the study which included open and closed-ended questions. Fishers Exact Test was used to analyse associations in non parametric categorical data. RESULTS: 243 children were recruited into the PIVOT study. Of a possible 235, 136 questionnaires were returned (response rate 59%). Of those questionnaires returned; 98% of parents remembered consenting, 95% felt they were given enough time to make their decision and 96% felt they received enough information. Major reasons for participation were benefit to other children in the future 31%, contribution to science 27%, benefit to their own child 18%. Most parents (85%) did not feel obliged to participate. 62% felt there was an advantage to taking part and 18% felt there was a disadvantage. 91% of parents said they would take part in a similar study in the future, stating influences on their decision being benefit to their own child (91%) and benefit to all children (89%). CONCLUSION: The major motivation in parents consenting for their previously well child to participate in an RCT of therapy for an acute medical illness was to increase medical knowledge in the future. Most saw an advantage in taking part in the trial and did not feel obliged to participate. PMID- 17349035 TI - Delayed diagnosis of coeliac disease increases cancer risk. AB - BACKGROUND: The association between coeliac disease (CD) and neoplasms has been long established, but few data are available about the risk factors. The aim of this paper is to estimate the risk of developing a neoplasm among non diagnosed coeliac patients and to evaluate if this risk correlates with the age of patients at diagnosis of coeliac disease. METHODS: The study population consists of patients (n = 1968) diagnosed with CD at 20 Italian gastroenterology referral Centers between 1st January 1982 and 31st March 2005. RESULTS: The SIR for all cancers resulted to be 1.3; 95% CI = 1.0-1.7 p < 0.001. The specific SIRs for non Hodgkin lymphoma was 4.7; 95% CI = 2.9-7.3 p < 0.001, for the small bowel carcinoma 25; 95% CI = 8.5-51.4 p < 0.001, for non Hodgkin lymphoma 10; 95% CI = 2.7-25 p = 0.01, finally for the stomach carcinoma 3; 95% CI = 1.3-4.9 p < 0.08. The mean age at diagnosis of CD of patients that developed sooner or later a neoplasm was 47,6 +/- 10.2 years versus 28.6 +/- 18.2 years of patients who did not. CONCLUSION: Coeliac patients have an increased risk of developing cancer in relation to the age of diagnosis of CD. This risk results higher for malignancies of the gastro-intestinal sites. An accurate screening for tumors should be performed in patients diagnosed with CD in adulthood and in advancing age. PMID- 17349036 TI - Hawkeye: an interactive visual analytics tool for genome assemblies. AB - Genome sequencing remains an inexact science, and genome sequences can contain significant errors if they are not carefully examined. Hawkeye is our new visual analytics tool for genome assemblies, designed to aid in identifying and correcting assembly errors. Users can analyze all levels of an assembly along with summary statistics and assembly metrics, and are guided by a ranking component towards likely mis-assemblies. Hawkeye is freely available and released as part of the open source AMOS project http://amos.sourceforge.net/hawkeye. PMID- 17349037 TI - Quantifying the metabolic capabilities of engineered Zymomonas mobilis using linear programming analysis. AB - BACKGROUND: The need for discovery of alternative, renewable, environmentally friendly energy sources and the development of cost-efficient, "clean" methods for their conversion into higher fuels becomes imperative. Ethanol, whose significance as fuel has dramatically increased in the last decade, can be produced from hexoses and pentoses through microbial fermentation. Importantly, plant biomass, if appropriately and effectively decomposed, is a potential inexpensive and highly renewable source of the hexose and pentose mixture. Recently, the engineered (to also catabolize pentoses) anaerobic bacterium Zymomonas mobilis has been widely discussed among the most promising microorganisms for the microbial production of ethanol fuel. However, Z. mobilis genome having been fully sequenced in 2005, there is still a small number of published studies of its in vivo physiology and limited use of the metabolic engineering experimental and computational toolboxes to understand its metabolic pathway interconnectivity and regulation towards the optimization of its hexose and pentose fermentation into ethanol. RESULTS: In this paper, we reconstructed the metabolic network of the engineered Z. mobilis to a level that it could be modelled using the metabolic engineering methodologies. We then used linear programming (LP) analysis and identified the Z. mobilis metabolic boundaries with respect to various biological objectives, these boundaries being determined only by Z. mobilis network's stoichiometric connectivity. This study revealed the essential for bacterial growth reactions and elucidated the association between the metabolic pathways, especially regarding main product and byproduct formation. More specifically, the study indicated that ethanol and biomass production depend directly on anaerobic respiration stoichiometry and activity. Thus, enhanced understanding and improved means for analyzing anaerobic respiration and redox potential in vivo are needed to yield further conclusions for potential genetic targets that may lead to optimized Z. mobilis strains. CONCLUSION: Applying LP to study the Z. mobilis physiology enabled the identification of the main factors influencing the accomplishment of certain biological objectives due to metabolic network connectivity only. This first level metabolic analysis model forms the basis for the incorporation of more complex regulatory mechanisms and the formation of more realistic models for the accurate simulation of the in vivo Z. mobilis physiology. PMID- 17349038 TI - Factors influencing publication choice: why faculty choose open access. AB - BACKGROUND: In an attempt to identify motivating factors involved in decisions to publish in open access and open archives (OA) journals, individual interviews with biomedical faculty members at the University of North Carolina at Chapel Hill (UNC-Chapel Hill) and Duke University, two major research universities, were conducted. The interviews focused on faculty identified as early adopters of OA/free full-text publishing. METHODS: Searches conducted in PubMed and PubMed Central identified faculty from the two institutions who have published works in OA/free full-text journals. The searches targeted authors with multiple OA citations during a specified 18 month period. Semi-structured interviews were conducted with the most prolific OA authors at each university. Individual interviews attempted to determine whether the authors were aware they published in OA journals, why they chose to publish in OA journals, what factors influenced their publishing decisions, and their general attitude towards OA publishing models. RESULTS & DISCUSSION: Fourteen interviews were granted and completed. Respondents included a fairly even mix of Assistant, Associate and Full professors. Results indicate that when targeting biomedical faculty at UNC-Chapel Hill and Duke, speed of publication and copyright retention are unlikely motivating factors or incentives for the promotion of OA publishing. In addition, author fees required by some open access journals are unlikely barriers or disincentives. CONCLUSION: It appears that publication quality is of utmost importance when choosing publication venues in general, while free access and visibility are specifically noted incentives for selection of OA journals. Therefore, free public availability and increased exposure may not be strong enough incentives for authors to choose open access over more traditional and respected subscription based publications, unless the quality issue is also addressed. PMID- 17349039 TI - Common carotid artery wall thickness and external diameter as predictors of prevalent and incident cardiac events in a large population study. AB - BACKGROUND: Arterial diameters enlarge in response to wall thickening, plaques, and many atherosclerotic risk factors. We hypothesized that right common carotid artery (RCCA) diameter would be independently associated with cardiac disease and improve risk discrimination. METHODS: In a middle-aged, biracial population (baseline n = 11225), we examined associations between 1 standard deviation increments of baseline RCCA diameter with prevalent myocardial infarction (MI) and incident cardiac events (MI or cardiac death) using logistic regression and Cox proportional hazards models, respectively. Areas under the receiver operator characteristic curve (AUC) were used to estimate model discrimination. RESULTS: MI was present in 451 (4%) participants at baseline (1987-89), and incident cardiac events occurred among 646 (6%) others through 1999. Adjusting for IMT, RCCA diameter was associated with prevalent MI (female OR = 2.0, 95%CI = 1.61 2.49; male OR = 1.16, 95% CI = 1.04-1.30) and incident cardiac events (female HR = 1.75, 95% CI = 1.51-2.02; male HR = 1.27, 95% CI = 1.15-1.40). Associations were attenuated but persisted after adjustment for risk factors (not including IMT) (prevalent MI: female OR = 1.73, 95% CI = 1.40-2.14; male OR = 1.14, 95% CI = 1.02-1.28, and incident cardiac events: female HR = 1.26, 95% CI = 1.08-1.48; male HR = 1.19, 95% CI = 1.08-1.32). After additional adjustment for IMT, diameter was associated with incident cardiac events in women (HR = 1.18, 95% CI = 1.00-1.40) and men (HR = 1.17, 95% CI = 1.06-1.29), and with prevalent MI only in women (OR = 1.73; 95% CI = 1.37-2.17). In women, when adjustment was limited, diameter models had larger AUC than other models. CONCLUSION: RCCA diameter is an important correlate of cardiac events, independent of IMT, but adds little to overall risk discrimination after risk factor adjustment. PMID- 17349040 TI - Model based analysis of real-time PCR data from DNA binding dye protocols. AB - BACKGROUND: Reverse transcription followed by real-time PCR is widely used for quantification of specific mRNA, and with the use of double-stranded DNA binding dyes it is becoming a standard for microarray data validation. Despite the kinetic information generated by real-time PCR, most popular analysis methods assume constant amplification efficiency among samples, introducing strong biases when amplification efficiencies are not the same. RESULTS: We present here a new mathematical model based on the classic exponential description of the PCR, but modeling amplification efficiency as a sigmoidal function of the product yield. The model was validated with experimental results and used for the development of a new method for real-time PCR data analysis. This model based method for real time PCR data analysis showed the best accuracy and precision compared with previous methods when used for quantification of in-silico generated and experimental real-time PCR results. Moreover, the method is suitable for the analyses of samples with similar or dissimilar amplification efficiency. CONCLUSION: The presented method showed the best accuracy and precision. Moreover, it does not depend on calibration curves, making it ideal for fully automated high-throughput applications. PMID- 17349041 TI - Automated detection of regions of interest for tissue microarray experiments: an image texture analysis. AB - BACKGROUND: Recent research with tissue microarrays led to a rapid progress toward quantifying the expressions of large sets of biomarkers in normal and diseased tissue. However, standard procedures for sampling tissue for molecular profiling have not yet been established. METHODS: This study presents a high throughput analysis of texture heterogeneity on breast tissue images for the purpose of identifying regions of interest in the tissue for molecular profiling via tissue microarray technology. Image texture of breast histology slides was described in terms of three parameters: the percentage of area occupied in an image block by chromatin (B), percentage occupied by stroma-like regions (P), and a statistical heterogeneity index H commonly used in image analysis. Texture parameters were defined and computed for each of the thousands of image blocks in our dataset using both the gray scale and color segmentation. The image blocks were then classified into three categories using the texture feature parameters in a novel statistical learning algorithm. These categories are as follows: image blocks specific to normal breast tissue, blocks specific to cancerous tissue, and those image blocks that are non-specific to normal and disease states. RESULTS: Gray scale and color segmentation techniques led to identification of same regions in histology slides as cancer-specific. Moreover the image blocks identified as cancer-specific belonged to those cell crowded regions in whole section image slides that were marked by two pathologists as regions of interest for further histological studies. CONCLUSION: These results indicate the high efficiency of our automated method for identifying pathologic regions of interest on histology slides. Automation of critical region identification will help minimize the inter-rater variability among different raters (pathologists) as hundreds of tumors that are used to develop an array have typically been evaluated (graded) by different pathologists. The region of interest information gathered from the whole section images will guide the excision of tissue for constructing tissue microarrays and for high throughput profiling of global gene expression. PMID- 17349042 TI - An experimental test for indirect benefits in Drosophila melanogaster. AB - BACKGROUND: Despite much empirical attention, tests for indirect benefits of mate choice have rarely considered the major components of sexual and nonsexual offspring fitness relevant to a population. Here we use a novel experimental design to test for the existence of any indirect benefits in a laboratory adapted population of D. melanogaster. Our experiment compared the fitness (mating success, longevity, and productivity) of individuals possessing genomes that derived two generations previously from males that were either entirely successful (studs) or wholly unsuccessful (duds) at achieving mates in three subsequent rounds of mating trials. RESULTS: Males from the stud treatment were 30% more successful on average at securing mates than males from the dud treatment. In contrast, we found no difference between treatments in measures of productivity or of longevity when measured in a mixed-sex environment. In the absence of females, however, males in the stud treatment outlived males in the dud treatment. CONCLUSION: Our results suggest that mating with successful males in this population provides an indirect benefit to females and that, at least in this environment, the benefit arises primarily through the production of more attractive male offspring. However, it is unclear whether this represents solely a traditional sexy sons benefit or whether there is an additional good genes component (with male offspring simply allocating their surplus condition to traits that enhance their mating success). The lack of any detectable differences in female fitness between the two treatments suggests the former, although the longevity advantage of males in the stud treatment when females were absent is consistent with the latter. Determining the effect of this indirect benefit on the evolution of female mate preferences (or resistance) will require comparable data on the direct costs of mating with various males, and an understanding of how these costs and benefits integrate across generations and vary among environments. PMID- 17349043 TI - Towards a comprehensive structural coverage of completed genomes: a structural genomics viewpoint. AB - BACKGROUND: Structural genomics initiatives were established with the aim of solving protein structures on a large-scale. For many initiatives, such as the Protein Structure Initiative (PSI), the primary aim of target selection is focussed towards structurally characterising protein families which, so far, lack a structural representative. It is therefore of considerable interest to gain insights into the number and distribution of these families, and what efforts may be required to achieve a comprehensive structural coverage across all protein families. RESULTS: In this analysis we have derived a comprehensive domain annotation of the genomes using CATH, Pfam-A and Newfam domain families. We consider what proportions of structurally uncharacterized families are accessible to high-throughput structural genomics pipelines, specifically those targeting families containing multiple prokaryotic orthologues. In measuring the domain coverage of the genomes, we show the benefits of selecting targets from both structurally uncharacterized domain families, whilst in addition, pursuing additional targets from large structurally characterised protein superfamilies. CONCLUSION: This work suggests that such a combined approach to target selection is essential if structural genomics is to achieve a comprehensive structural coverage of the genomes, leading to greater insights into structure and the mechanisms that underlie protein evolution. PMID- 17349044 TI - Structural investigations of the ferredoxin and terminal oxygenase components of the biphenyl 2,3-dioxygenase from Sphingobium yanoikuyae B1. AB - BACKGROUND: The initial step involved in oxidative hydroxylation of monoaromatic and polyaromatic compounds by the microorganism Sphingobium yanoikuyae strain B1 (B1), previously known as Sphingomonas yanoikuyae strain B1 and Beijerinckia sp. strain B1, is performed by a set of multiple terminal Rieske non-heme iron oxygenases. These enzymes share a single electron donor system consisting of a reductase and a ferredoxin (BPDO-FB1). One of the terminal Rieske oxygenases, biphenyl 2,3-dioxygenase (BPDO-OB1), is responsible for B1's ability to dihydroxylate large aromatic compounds, such as chrysene and benzo[a]pyrene. RESULTS: In this study, crystal structures of BPDO-OB1 in both native and biphenyl bound forms are described. Sequence and structural comparisons to other Rieske oxygenases show this enzyme to be most similar, with 43.5 % sequence identity, to naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4. While structurally similar to naphthalene 1,2-dioxygenase, the active site entrance is significantly larger than the entrance for naphthalene 1,2 dioxygenase. Differences in active site residues also allow the binding of large aromatic substrates. There are no major structural changes observed upon binding of the substrate. BPDO-FB1 has large sequence identity to other bacterial Rieske ferredoxins whose structures are known and demonstrates a high structural homology; however, differences in side chain composition and conformation around the Rieske cluster binding site are noted. CONCLUSION: This is the first structure of a Rieske oxygenase that oxidizes substrates with five aromatic rings to be reported. This ability to catalyze the oxidation of larger substrates is a result of both a larger entrance to the active site as well as the ability of the active site to accommodate larger substrates. While the biphenyl ferredoxin is structurally similar to other Rieske ferredoxins, there are distinct changes in the amino acids near the iron-sulfur cluster. Because this ferredoxin is used by multiple oxygenases present in the B1 organism, this ferredoxin-oxygenase system provides the structural platform to dissect the balance between promiscuity and selectivity in protein-protein electron transport systems. PMID- 17349045 TI - Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka. AB - BACKGROUND: Single nucleotide polymorphisms (SNPs) in the Plasmodium vivax dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pvdhps) genes cause parasite resistance to the antifolate drug combination, sulphadoxine/pyrimethamine (SP). Monitoring these SNPs provide insights into the level of drug pressure caused by SP use and presumably other antifolate drugs. In Sri Lanka, chloroquine (CQ) with primaquine (PQ) and SP with PQ is used as first and second line treatment, respectively, against uncomplicated Plasmodium falciparum and/or P. vivax infections. CQ/PQ is still efficacious against P. vivax infections, thus SP is rarely used and it is assumed that the prevalence of SNPs related to P. vivax SP resistance is low. However, this has not been assessed in Sri Lanka as in most other parts of Asia. This study describes the prevalence and distribution of SNPs related to P. vivax SP resistance across Sri Lanka. SUBJECTS AND METHODS: P. vivax-positive samples were collected from subjects presenting at government health facilities across nine of the major malaria endemic districts on the island. The samples were analysed for SNPs/haplotypes at codon 57, 58, 61 and 117 of the Pvdhfr gene and 383, 553 and 585 of the Pvdhps gene by applying PCR followed by a hybridization step using sequence specific oligonucleotide probes (SSOPs) in an ELISA format. RESULTS: In the study period, the government of Sri Lanka recorded 2,149 P. vivax cases from the nine districts out of which, 454 (21.1%) blood samples were obtained. Pvdhfr haplotypes could be constructed for 373 of these. The FSTS wild-haplotype was represented in 257 samples (68.9%), the double mutant LRTS haplotype was the most frequently observed mutant (24.4%) while the triple mutation (LRTN) was only identified once. Except for two samples of the single mutated Pvdhps GAV haplotype, the remaining samples were wildtype. Geographical differences were apparent, notably a significantly higher frequency of mutant Pvdhfr haplotypes was observed in the Northern districts. CONCLUSION: Since SP is rarely used in Sri Lanka, the high frequency and diversity of Pvdhfr mutations was unexpected indicating the emergence of drug resistant parasites despite a low level of SP drug pressure. PMID- 17349046 TI - The exceptional stem cell system of Macrostomum lignano: screening for gene expression and studying cell proliferation by hydroxyurea treatment and irradiation. AB - BACKGROUND: Flatworms are characterized by an outstanding stem cell system. These stem cells (neoblasts) can give rise to all cell types including germ cells and power the exceptional regenerative capacity of many flatworm species. Macrostomum lignano is an emerging model system to study stem cell biology of flatworms. It is complementary to the well-studied planarians because of its small size, transparency, simple culture maintenance, the basal taxonomic position and its less derived embryogenesis that is more closely related to spiralians. The development of cell-, tissue- and organ specific markers is necessary to further characterize the differentiation potential of flatworm stem cells. Large scale in situ hybridization is a suitable tool to identify possible markers. Distinguished genes identified in a large scale screen in combination with manipulation of neoblasts by hydroxyurea or irradiation will advance our understanding of differentiation and regulation of the flatworm stem cell system. RESULTS: We have set up a protocol for high throughput large scale whole mount in situ hybridization for the flatworm Macrostomum lignano. In the pilot screen, a number of cell-, tissue- or organ specific expression patterns were identified. We have selected two stem cell- and germ cell related genes--macvasa and macpiwi--and studied effects of hydroxyurea (HU) treatment or irradiation on gene expression. In addition, we have followed cell proliferation using a mitosis marker and bromodeoxyuridine labeling of S-phase cells after various periods of HU exposure or different irradiation levels. HU mediated depletion of cell proliferation and HU induced reduction of gene expression was used to generate a cDNA library by suppressive subtractive hybridization. 147 differentially expressed genes were sequenced and assigned to different categories. CONCLUSION: We show that Macrostomum lignano is a suitable organism to perform high throughput large scale whole mount in situ hybridization. Genes identified in such screens--together with BrdU/H3 labeling--can be used to obtain information on flatworm neoblasts. PMID- 17349047 TI - The role of MUC1 and MUC3 in the biology and prognosis of colorectal cancer. AB - BACKGROUND: MUC1 and MUC3 are from a large family of glycoproteins with an aberrant expression profile in various malignancies. Much interest has been focused on the role of these proteins in the development and progression of colorectal cancer; however, no previous studies have included the highly confounding variable of vascular invasion in their survival analysis. Using high throughput tissue microarray technology we assessed the prognostic value of MUC1 and MUC3 expression in the largest cohort of colorectal cancer patients to date. We propose that tumours lacking expression of MUC1 and MUC3 will be more likely to metastasise, due to previously observed loss of cell-cell adhesion, and this will therefore lead to more aggressive cancers with poorer prognosis. METHODS: A tissue micro-array was prepared from tumour samples of 462 consecutive patients undergoing resection of a primary colorectal cancer. A comprehensive prospectively recorded data base with mean follow up of 75 months was collected and included common clinicopathological variables and disease specific survival. Immunohistochemical analysis of MUC1 and MUC3 expression was performed using antibodies NCL-MUC1 and 1143/B7 respectively, results were correlated with the variables within the database. RESULTS: Positive expression of MUC1 and MUC3 was seen in 32% and 74% of tumours respectively. On univariate analysis no correlation was seen with either MUC1 or MUC3 and any of the clinicopathological variables including tumour grade and stage, vascular invasion and tumour type. Kaplan-Meier analysis demonstrated a significant reduction in disease specific survival with MUC1 positive tumours (p = 0.038), this was not seen with MUC3 (p = 0.552). On multivariate analysis, using Cox proportional hazards model, MUC1 expression was shown to be an independent marker of prognosis (HR 1.339, 95%CI 1.002-1.790, p = 0.048). CONCLUSION: MUC1 expression in colorectal cancer is an independent marker of poor prognosis, even when vascular invasion is included in the analysis. These results support previous studies suggesting a role for MUC1 in colorectal cancer development possibly through its effects on cell adhesion. PMID- 17349048 TI - Transplacental murine cytomegalovirus infection in the brain of SCID mice. AB - BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most common congenital viral infection in humans and the major nonhereditary cause of central nervous system (CNS) developmental disorders. Previous attempts to develop a murine CMV (MCMV) model of natural congenital human CMV (HCMV) infection have failed because MCMV does not cross the placenta in immunocompetent mice. RESULTS: In marked contrast with immunocompetent mice, C.B-17 SCID (severe combined immunodeficient) mice were found to be highly susceptible to natural MCMV transplacental transmission and congenital infection. Timed-pregnant SCID mice were intraperitoneally (IP) injected with MCMV at embryonic (E) stages E0-E7, and vertical MCMV transmission was evaluated using nested polymerase chain reaction (nPCR), in situ hybridization (ISH) and immunohistochemical (IHC) assays. SCID mouse dams IP injected at E0 with 102 PFU of MCMV died or resorbed their fetuses by E18. Viable fetuses collected at E18 from SCID mice IP injected with 102-104 PFU of MCMV at E7 did not demonstrate vertical MCMV transmission. Notably, transplacental MCMV transmission was confirmed in E18 fetuses from SCID mice IP injected with 103 PFU of MCMV at stages E3-E5. The maximum rate of transplacental MCMV transmission (53%) at E18 occurred when SCID mouse dams were IP injected with 103 PFU of MCMV at E4. Congenital infection was confirmed by IHC immunostaining of MCMV antigens in 26% of the MCMV nPCR positive E18 fetuses. Transplacental MCMV transmission was associated with intrauterine growth retardation and microcephaly. Additionally, E18 fetuses with MCMV nPCR positive brains had cerebral interleukin-1alpha (IL-1alpha) expression significantly upregulated and cerebral IL-1 receptor II (IL-1RII) transcription significantly downregulated. However, MCMV-induced changes in cerebral cytokine expression were not associated with any histological signs of MCMV infection or inflammation in the brain. CONCLUSION: Severe T- and B-cell immunodeficiencies in SCID mice significantly enhance the rate of natural MCMV transplacental transmission and congenital infection. During gestation MCMV exhibits a tissue tropism for the developing brain, and vertical MCMV transmission is correlated with fetal growth retardation and abnormal cerebral proinflammatory cytokine expression. These data confirm that natural vertical MCMV infection in SCID mice constitutes a useful new experimental rodent model of congenital HCMV infection. PMID- 17349049 TI - Knowledge of pressure ulcer prevention: a cross-sectional and comparative study among nurses. AB - BACKGROUND: Pressure ulcers are a common, painful and costly condition. Results of a 1991 study into the knowledge among Dutch hospital nurses on the usefulness of measures to prevent pressure ulcers showed moderate knowledge. Results were confirmed by subsequent studies. In recent years, Dutch guidelines have been updated and the attention given to pressure ulcer care has been increased. This was expected to improve pressure ulcer care and to increase nurses' knowledge. The aims of the current study were to investigate (1) how much nurses employed in Dutch hospitals know about the usefulness of 28 preventive measures considered in the most recent national pressure ulcer guideline; (2) whether differences in knowledge exist between nurses working in hospitals that audit pressure ulcers and those employed in hospitals that do not; and (3) to study whether knowledge among Dutch hospital nurses regarding the usefulness of preventive measures had changed between 1991 and 2003. METHODS: A cross-sectional study design among nurses employed in Dutch hospitals in 2003 was used to investigate their knowledge and differences in knowledge between nurses employed in different types of institution. A comparative design was used to assess whether knowledge differed between this population and that of Dutch hospital nurses in 1991. The nurses' knowledge was assessed by a written questionnaire. Data of 522 respondents meeting the inclusion criteria were analyzed and compared with the results of the 351 nurses included in the 1991 study. RESULTS: Knowledge in 2003 was slightly better than that in 1991. The nurses were moderately aware of the usefulness of preventive measures. Nurses employed in organizations that monitored pressure ulcers did not display greater knowledge than those employed in organizations that did not do so. CONCLUSION: Knowledge among Dutch hospital nurses about the usefulness of measures to prevent pressure ulcers seems to be moderate. Being employed in an institution that monitors pressure ulcer care hardly affects the knowledge level. Knowledge about prevention has improved little since 1991. PMID- 17349050 TI - Effects of residence and race on burden of travel for care: cross sectional analysis of the 2001 US National Household Travel Survey. AB - BACKGROUND: Travel burden is a key element in conceptualizing geographic access to health care. Prior research has shown that both rural and minority populations bear disproportionate travel burdens. However, many studies are limited to specific types of patient or specific locales. The purpose of our study was to quantify geographic and race-based differences in distance traveled and time spent in travel for medical/dental care using representative national data. METHODS: Data were drawn from 2001 National Household Travel Survey (NHTS), a nationally representative, cross-sectional household survey conducted by the US Department of Transportation. Participants recorded all travel on a designated day; the overall response rate was 41%. Analyses were restricted to households reporting at least one trip for medical and/or dental care; 3,914 trips made by 2,432 households. Dependent variables in the analysis were road miles traveled, minutes spent traveling, and high travel burden, defined as more than 30 miles or 30 minutes per trip. Independent variables of interest were rural residence and race. Characteristics of the individual, the trip, and the community were controlled in multivariate analyses. RESULTS: The average trip for care in the US in 2001 entailed 10.2 road miles (16.4 kilometers) and 22.0 minutes of travel. Rural residents traveled further than urban residents in unadjusted analysis (17.5 versus 8.3 miles; 28.2 versus 13.4 km). Rural trips took 31.4% longer than urban trips (27.2 versus 20.7 minutes). Distance traveled did not vary by race. African Americans spent more time in travel than whites (29.1 versus 20.6 minutes); other minorities did not differ. In adjusted analyses, rural residence (odds ratio, OR, 2.67, 95% confidence interval, CI 1.39 5.1.5) was associated with a trip of 30 road miles or more; rural residence (OR, 1.80, CI 1.09 2.99) and African American race/ethnicity (OR 3.04. 95% CI 2.0 4.62) were associated with a trip lasting 30 minutes or longer. CONCLUSION: Rural residents and African Americans experience higher travel burdens than urban residents or whites when seeking medical/dental care. PMID- 17349052 TI - Can cancer patients assess the influence of pain on functions? A randomised, controlled study of the pain interference items in the Brief Pain Inventory. AB - BACKGROUND: The Brief Pain Inventory (BPI) is recommended as a pain measurement tool by the Expert Working Group of the European Association of Palliative Care. The BPI is designed to assess both pain severity and interference with functions caused by pain. The purpose of this study was to investigate if pain interference items are influenced by other factors than pain. METHODS: We asked adult cancer patients to complete the original and a revised BPI on two study days. In the original version of the BPI the patients were asked how, during the last 24 hours, pain has interfered with functions. In the revised BPI this question was changed to how, during the last 24 hours, these functions are affected in general. Heath related quality of life was assessed at both study days applying the European Organization for Research and Treatment of Cancer quality of life questionnaire. RESULTS: Forty-eight of the 55 included patients completed both assessments. The BPI pain intensities scores and the health related quality of life scores were similar at the two study days. Except for mood this study observed no significant distinctions between the patients' BPI interference items scores in the original (pain influence on function) and the revised BPI (function in general). Seventeen patients reported higher influence from pain on functions than the total influence on function from all causes. CONCLUSION: We observed similar scores in the original BPI interference scores (pain influence on function) compared with the revised BPI interference scores (decreased function in general). This finding might imply that the BPI interference scale measures are partly responded to as more of a global interference measure. PMID- 17349051 TI - Cocaine- and opiate-related fatal overdose in New York City, 1990-2000. AB - BACKGROUND: In New York City (NYC), the annual mortality rate is higher for accidental drug overdoses than for homicides; cocaine and opiates are the drugs most frequently associated with drug overdose deaths. We assessed trends and correlates of cocaine- and opiate-related overdose deaths in NYC during 1990 2000. METHODS: Data were collected from the NYC Office of the Chief Medical Examiner (OCME) on all fatal drug overdoses involving cocaine and/or opiates that occurred between 1990-2000 (n = 8,774) and classified into three mutually exclusive groups (cocaine only; opiates-only; cocaine and opiates). Risk factors for accidental overdose were examined in the three groups and compared using multinomial logistic regression. RESULTS: Overall, among decedents ages 15-64, 2,392 (27.3%) were attributed to cocaine only and 2,825 (32.2%) were attributed to opiates-only. During the interval studied, the percentage of drug overdose deaths attributed to cocaine only fell from 29.2% to 23.6% while the percentage of overdose deaths attributed to opiates-only rose from 30.6% to 40.1%. Compared to New Yorkers who fatally overdosed from opiates-only, fatal overdose attributed to cocaine-only was associated with being male (OR = 0.71, 95% CI 0.62-0.82), Black (OR = 4.73, 95% CI 4.08-5.49) or Hispanic (OR = 1.51, 95% CI 1.29-1.76), an overdose outside of a residence or building (OR = 1.34, 95% CI 1.06-1.68), having alcohol detected at autopsy (OR = 0.50, 95% CI 0.44-0.56) and older age (55-64) (OR = 2.53 95% CI 1.70-3.75)). CONCLUSION: As interventions to prevent fatal overdose become more targeted and drug specific, understanding the different populations at risk for different drug-related overdoses will become more critical. PMID- 17349053 TI - Personality styles in patients with fibromyalgia, major depression and healthy controls. AB - BACKGROUND: The fibromyalgia syndrome (FMS) is suggested to be a manifestation of depression or affective spectrum disorder. We measured the cognitive style of patients with FMS to assess personality styles in 44 patients with fibromyalgia syndrome (FMS) by comparing them with 43 patients with major depressive disorder (MDD) and 41 healthy controls (HC). METHODS: Personality styles were measured by the Sociotropy and Autonomy Scale (SAS) and the Dysfunctional Attitude Scale (DAS). The Structured Clinical interview for DSM Axis I was applied to Axis I disorders, while the Beck Depression Inventory was used to measure depression severity. RESULTS: Patients with FMS in general have a sociotropic personality style similar to patients with MDD, and different from HC, but FMS patients without a lifetime history of MDD had a cognitive personality style different from patients with MDD and similar to HC. CONCLUSION: These findings suggest that a depressotypic personality style is related to depressive disorder, but not to FMS. PMID- 17349054 TI - Neonatal diabetes mellitus: a disease linked to multiple mechanisms. AB - Transient (TNDM) and Permanent (PNDM) Neonatal Diabetes Mellitus are rare conditions occurring in 1:300,000-400,000 live births. TNDM infants develop diabetes in the first few weeks of life but go into remission in a few months, with possible relapse to a permanent diabetes state usually around adolescence or as adults. The pancreatic dysfunction in this condition may be maintained throughout life, with relapse initiated at times of metabolic stress such as puberty or pregnancy. In PNDM, insulin secretory failure occurs in the late fetal or early post-natal period and does not go into remission. Patients with TNDM are more likely to have intrauterine growth retardation and less likely to develop ketoacidosis than patients with PNDM. In TNDM, patients are younger at the diagnosis of diabetes and have lower initial insulin requirements. Considerable overlap occurs between the two groups, so that TNDM cannot be distinguished from PNDM based on clinical features. Very early onset diabetes mellitus seems to be unrelated to autoimmunity in most instances. A number of conditions are associated with PNDM, some of which have been elucidated at the molecular level. Among these, the very recently elucidated mutations in the KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunit of the pancreatic KATP channel involved in regulation of insulin secretion, account for one third to half of the PNDM cases. Molecular analysis of chromosome 6 anomalies (found in more than 60% in TNDM), and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1, provides a tool to identify TNDM from PNDM in the neonatal period. This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 genes, from insulin therapy to sulfonylureas. Recurrent diabetes is common in patients with "transient" neonatal diabetes mellitus and, consequently, prolonged follow-up is imperative. Realizing how difficult it is to take care of a child of this age with diabetes mellitus should prompt clinicians to transfer these children to specialized centers. Insulin therapy and high caloric intake are the basis of the treatment. Insulin pump may offer an interesting therapeutic tool in this age group in experienced hands. PMID- 17349055 TI - Fracture prevention with vitamin D supplementation: considering the inconsistent results. AB - BACKGROUND: A meta-analysis found that high dose vitamin D, different from low dose, decreased fracture risk by 23% for any nonvertebral fracture and by 26% for hip fracture. Unfortunately, however, this effect was not confirmed by recent trials. The aim of this paper is to explore if this inconsistency can be attributed to publication bias or heterogeneity of the trials. METHODS: The meta analysis was extended with recent randomised controlled trials (RCTs) that were identified by a systematic review. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from raw data. A funnel plot was used to explore the possibility of publication bias. Forest plots were used to investigate if vitamin D dose, concurrent use of calcium and target population were sources of heterogeneity. Linear regression analysis of log RR on adherence rate and achieved vitamin D level was used to study whether these variables were associated with fracture risk. RESULTS: A total of eleven trials was included: seven RCTs from the meta-analysis and four recently published. For any nonvertebral fracture, the funnel plot was asymmetrical because two small RCTs showed a large positive effect. This was not found for hip fracture. As reported in the meta-analysis, low dose vitamin D (<400 IU daily) was not effective. In contrast to the meta-analysis, however, the effect of high dose vitamin D (> or =700 IU daily) seemed to be dependent on target population. For any nonvertebral fracture, the pooled RR was 0.80 (95% CI, 0.70-0.90) in institutionalised persons, and 0.88 (95% CI, 0.75-1.04) in the general population; for hip fracture, pooled RR 0.72 (95% CI, 0.59 to 0.88) and 1.04 (95% CI, 0.72-1.50), respectively. Other sources of heterogeneity were not clearly found. In the meta analysis, pooled RRs were mainly based on small trials that showed a large effect or trials in institutionalised persons. CONCLUSION: It is likely that the inconsistency between the meta-analysis and the recent trials is, at least partially, due to publication bias and differences in target population. High dose vitamin D may be effective in institutionalised persons but probably is not effective in the general population. PMID- 17349057 TI - Biomechanical effects of polyaxial pedicle screw fixation on the lumbosacral segments with an anterior interbody cage support. AB - BACKGROUND: Lumbosacral fusion is a relatively common procedure that is used in the management of an unstable spine. The anterior interbody cage has been involved to enhance the stability of a pedicle screw construct used at the lumbosacral junction. Biomechanical differences between polyaxial and monoaxial pedicle screws linked with various rod contours were investigated to analyze the respective effects on overall construct stiffness, cage strain, rod strain, and contact ratios at the vertebra-cage junction. METHODS: A synthetic model composed of two ultrahigh molecular weight polyethylene blocks was used with four titanium pedicle screws (two in each block) and two rods fixation to build the spinal construct along with an anterior interbody cage support. For each pair of the construct fixed with polyaxial or monoaxial screws, the linked rods were set at four configurations to simulate 0 degrees, 7 degrees, 14 degrees, and 21 degrees lordosis on the sagittal plane, and a compressive load of 300 N was applied. Strain gauges were attached to the posterior surface of the cage and to the central area of the left connecting rod. Also, the contact area between the block and the cage was measured using prescale Fuji super low pressure film for compression, flexion, lateral bending and torsion tests. RESULTS: Our main findings in the experiments with an anterior interbody cage support are as follows: 1) large segmental lordosis can decrease the stiffness of monoaxial pedicle screws constructs; 2) polyaxial screws rather than monoaxial screws combined with the cage fixation provide higher compression and flexion stiffness in 21 degrees segmental lordosis; 3) polyaxial screws enhance the contact surface of the cage in 21 degrees segmental lordosis. CONCLUSION: Polyaxial screws system used in conjunction with anterior cage support yields higher contact ratio, compression and flexion stiffness of spinal constructs than monoaxial screws system does in the same model when the spinal segment is set at large lordotic angles. Polyaxial pedicle screw fixation performs nearly equal percentages of vertebra-cage contact among all constructs with different sagittal alignments, therefore enhances the stabilization effect of interbody cages in the lumbosacral area. PMID- 17349056 TI - An internet survey of 2,596 people with fibromyalgia. AB - BACKGROUND: This study explored the feasibility of using an Internet survey of people with fibromyalgia (FM), with a view to providing information on demographics, sources of information, symptoms, functionality, perceived aggravating factors, perceived triggering events, health care utilization, management strategies, and medication use. METHODS: A survey questionnaire was developed by the National Fibromyalgia Association (NFA) in conjunction with a task force of "experts in the field". The questionnaire underwent several rounds of testing to improve its face validity, content validity, clarity and readability before it was mounted on the internet. The questionnaire consisted of 121 items and is available online at the website of the National Fibromyalgia Association. RESULTS: The questionnaire was completed by 2,569 people. Most were from the United States, with at least one respondent from each of the 50 states. Respondents were predominantly middle-aged Caucasian females, most of whom had FM symptoms for > or = 4 years. The most common problems were morning stiffness, fatigue, nonrestorative sleep, pain, concentration, and memory. Aggravating factors included: emotional distress, weather changes, insomnia, and strenuous activity. Respondents rated the most effective management modalities as rest, heat, pain medications, antidepressants, and hypnotics. The most commonly used medications were: acetaminophen, ibuprofen, naproxen, cyclobenzaprine, amitriptyline, and aspirin. The medications perceived to be the most effective were: hydrocodone preparations, aprazolam, oxycodone preparations, zolpidem, cyclobenzaprine, and clonazepam. CONCLUSION: This survey provides a snap-shot of FM at the end of 2005, as reported by a self-selected population of people. This descriptive data has a heuristic function, in that it identifies several issues for further research, such as the prescribing habits of FM health care providers, the role of emotional precipitants, the impact of obesity, the significance of low back pain and the nature of FM related stiffness. PMID- 17349058 TI - Geography and genography: prediction of continental origin using randomly selected single nucleotide polymorphisms. AB - BACKGROUND: Recent studies have shown that when individuals are grouped on the basis of genetic similarity, group membership corresponds closely to continental origin. There has been considerable debate about the implications of these findings in the context of larger debates about race and the extent of genetic variation between groups. Some have argued that clustering according to continental origin demonstrates the existence of significant genetic differences between groups and that these differences may have important implications for differences in health and disease. Others argue that clustering according to continental origin requires the use of large amounts of genetic data or specifically chosen markers and is indicative only of very subtle genetic differences that are unlikely to have biomedical significance. RESULTS: We used small numbers of randomly selected single nucleotide polymorphisms (SNPs) from the International HapMap Project to train naive Bayes classifiers for prediction of ancestral continent of origin. Predictive accuracy was tested on two independent data sets. Genetically similar groups should be difficult to distinguish, especially if only a small number of genetic markers are used. The genetic differences between continentally defined groups are sufficiently large that one can accurately predict ancestral continent of origin using only a minute, randomly selected fraction of the genetic variation present in the human genome. Genotype data from only 50 random SNPs was sufficient to predict ancestral continent of origin in our primary test data set with an average accuracy of 95%. Genetic variations informative about ancestry were common and widely distributed throughout the genome. CONCLUSION: Accurate characterization of ancestry is possible using small numbers of randomly selected SNPs. The results presented here show how investigators conducting genetic association studies can use small numbers of arbitrarily chosen SNPs to identify stratification in study subjects and avoid false positive genotype-phenotype associations. Our findings also demonstrate the extent of variation between continentally defined groups and argue strongly against the contention that genetic differences between groups are too small to have biomedical significance. PMID- 17349059 TI - Equity in health services use and intensity of use in Canada. AB - BACKGROUND: The Canadian health care system has striven to remove financial or other barriers to access to medically necessary health care services since the establishment of the Canada Health Act 20 years ago. Evidence has been conflicting as to what extent the Canadian health care system has met this goal of equitable access. The objective of this study was to examine whether and where socioeconomic inequities in health care utilization occur in Canada. METHODS: We used a nationally representative cross-sectional survey, the 2000/01 Canadian Community Health Survey, which provides a large sample size (about 110,000) and permits more comprehensive adjustment for need indicators than previous studies. We separately examined general practitioner, specialist, and hospital services using two-part hurdle models: use versus non-use by logistic regression, and the intensity of use among users by zero-truncated negative binomial regression. RESULTS: We found that lower income was associated with less contact with general practitioners, but among those who had contact, lower income and education were associated with greater intensity of use of general practitioners. Both lower income and education were associated with less contact with specialists, but there was no statistically significant relationship between these socioeconomic variables and intensity of specialist use among the users. Neither income nor education was statistically significantly associated with use or intensity of use of hospitals. CONCLUSION: Our study unveiled possible socioeconomic inequities in the use of health care services in Canada. PMID- 17349060 TI - GeneBins: a database for classifying gene expression data, with application to plant genome arrays. AB - BACKGROUND: To interpret microarray experiments, several ontological analysis tools have been developed. However, current tools are limited to specific organisms. RESULTS: We developed a bioinformatics system to assign the probe set sequences of any organism to a hierarchical functional classification modelled on KEGG ontology. The GeneBins database currently supports the functional classification of expression data from four Affymetrix arrays; Arabidopsis thaliana, Oryza sativa, Glycine max and Medicago truncatula. An online analysis tool to identify relevant functions is also provided. CONCLUSION: GeneBins provides resources to interpret gene expression results from microarray experiments. It is available at http://bioinfoserver.rsbs.anu.edu.au/utils/GeneBins/ PMID- 17349062 TI - A canonical FtsZ protein in Verrucomicrobium spinosum, a member of the Bacterial phylum Verrucomicrobia that also includes tubulin-producing Prosthecobacter species. AB - BACKGROUND: The origin and evolution of the homologous GTP-binding cytoskeletal proteins FtsZ typical of Bacteria and tubulin characteristic of eukaryotes is a major question in molecular evolutionary biology. Both FtsZ and tubulin are central to key cell biology processes--bacterial septation and cell division in the case of FtsZ and in the case of tubulins the function of microtubules necessary for mitosis and other key cytoskeleton-dependent processes in eukaryotes. The origin of tubulin in particular is of significance to models for eukaryote origins. Most members of domain Bacteria possess FtsZ, but bacteria in genus Prosthecobacter of the phylum Verrucomicrobia form a key exception, possessing tubulin homologs BtubA and BtubB. It is therefore of interest to know whether other members of phylum Verrucomicrobia possess FtsZ or tubulin as their FtsZ-tubulin gene family representative. RESULTS: Verrucomicrobium spinosum, a member of Phylum Verrucomicrobia of domain Bacteria, has been found to possess a gene for a protein homologous to the cytoskeletal protein FtsZ. The deduced amino acid sequence has sequence signatures and predicted secondary structure characteristic for FtsZ rather than tubulin, but phylogenetic trees and sequence analysis indicate that it is divergent from all other known FtsZ sequences in members of domain Bacteria. The FtsZ gene of V. spinosum is located within a dcw gene cluster exhibiting gene order conservation known to contribute to the divisome in other Bacteria and comparable to these clusters in other Bacteria, suggesting a similar functional role. CONCLUSION: Verrucomicrobium spinosum has been found to possess a gene for a protein homologous to the cytoskeletal protein FtsZ. The results suggest the functional as well as structural homology of the V. spinosum FtsZ to the FtsZs of other Bacteria implying its involvement in cell septum formation during division. Thus, both bacteria-like FtsZ and eukaryote like tubulin cytoskeletal homologs occur in different species of the phylum Verrucomicrobia of domain Bacteria, a result with potential major implications for understanding evolution of tubulin-like cytoskeletal proteins and the origin of eukaryote tubulins. PMID- 17349063 TI - Subaortic and midventricular obstructive hypertrophic cardiomyopathy with extreme segmental hypertrophy. AB - BACKGROUND: Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon. CASE PRESENTATION: A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM) was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II), but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler estimated 38 mm Hg gradient at rest); and a midventricular obstruction (Doppler estimated 43 mm Hg gradient), but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death. CONCLUSION: Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM). PMID- 17349064 TI - Cells of the synovium in rheumatoid arthritis. B cells. AB - There is significant evidence arising from experimental models that autoantibodies play a key role in the pathogenesis of inflammatory arthritis. In addition to autoantibody production, B cells efficiently present antigen to T cells, produce soluble factors, including cytokines and chemokines, and form B cell aggregates in the target organ of rheumatoid arthritis. In this review we analyze the multifaceted role that B cells play in the pathogenesis of rheumatoid arthritis and discuss how this information can be used to guide more specific targeting of B cells for the therapy of this disease. PMID- 17349061 TI - Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation. AB - BACKGROUND: The usage of synonymous codons shows considerable variation among mammalian genes. How and why this usage is non-random are fundamental biological questions and remain controversial. It is also important to explore whether mammalian genes that are selectively expressed at different developmental stages bear different molecular features. RESULTS: In two models of mouse stem cell differentiation, we established correlations between codon usage and the patterns of gene expression. We found that the optimal codons exhibited variation (AT- or GC-ending codons) in different cell types within the developmental hierarchy. We also found that genes that were enriched (developmental-pivotal genes) or specifically expressed (developmental-specific genes) at different developmental stages had different patterns of codon usage and local genomic GC (GCg) content. Moreover, at the same developmental stage, developmental-specific genes generally used more GC-ending codons and had higher GCg content compared with developmental pivotal genes. Further analyses suggest that the model of translational selection might be consistent with the developmental stage-related patterns of codon usage, especially for the AT-ending optimal codons. In addition, our data show that after human-mouse divergence, the influence of selective constraints is still detectable. CONCLUSION: Our findings suggest that developmental stage-related patterns of gene expression are correlated with codon usage (GC3) and GCg content in stem cell hierarchies. Moreover, this paper provides evidence for the influence of natural selection at synonymous sites in the mouse genome and novel clues for linking the molecular features of genes to their patterns of expression during mammalian ontogenesis. PMID- 17349065 TI - T cells and post menopausal osteoporosis in murine models. AB - Estrogen deficiency is one of the most frequent causes of osteoporosis in women and a possible cause of bone loss in men. But the mechanism involved remains largely unknown. Estrogen deficiency leads to an increase in the immune function, which culminates in an increased production of tumor necrosis factor (TNF) by activated T cells. TNF increases osteoclast formation and bone resorption both directly and by augmenting the sensitivity of maturing osteoclasts to the essential osteoclastogenic factor RANKL (the RANK ligand). Increased T cell production of TNF is induced by estrogen deficiency via a complex mechanism mediated by antigen presenting cells and the cytokines IFNgamma, IL-7 and transforming growth factor-beta. The experimental evidence that suggests that estrogen prevents bone loss by regulating T cell function and the interactions between immune cells and bone is reviewed here. PMID- 17349066 TI - Physical spousal violence against women in India: some risk factors. AB - Domestic spousal violence against women in developing countries like India, is now beginning to be recognized as a widespread health problem impeding development. This study aimed to explore the risk and protective factors for lifetime spousal physical violence. A cross-sectional household survey was carried out in rural, urban and urban-slum areas across seven sites in India, among women aged 15-49 years, living with a child less than 18 years of age. The sample was selected using the probability proportionate to size method. Trained field workers administered a structured questionnaire to elicit information on spousal physical violence. The main hypothesized variables were social support, witnessed father beating mother and experience of harsh physical violence during childhood, alcohol abuse by spouse and socioeconomic variables. The outcome variables included three physical violence behaviours of hit, kick and beat. Odds ratios were calculated for risk and protective factors of violence using logistic regression. Of 9938 women surveyed, 26% reported experiencing spousal physical violence during the lifetime of their marriage. Adjusted odds ratios calculated using multiple logistic regression analysis suggest that women whose husbands regularly consumed alcohol (OR 5.6; 95% CI 4.7-6.6); who experienced dowry harassment (OR 3.2; 95% CI 2.7-3.8); had reported experiencing harsh physical punishment during childhood (OR 1.6; 95% CI 1.4-1.8) and had witnessed their fathers beat their mothers (OR 1.9; 95% CI 1.6-2.1), were at increased risk of spousal physical violence (beat, hit and kick). Higher socioeconomic status and good social support acted as protective buffers against spousal physical violence. The findings provide compelling evidence of the potential risk factors for spousal physical violence, which in turn could help in planning interventions. PMID- 17349067 TI - Biosocial covariates of adult male body mass index in Central India. AB - Body mass index (BMI) is the 'measuring rod' of nutritional status. This study investigates the type and extent of correlation between adult male BMI and socioeconomic, cultural and bio-demographical variables using data from 11,496 individuals from 38 districts of Central India. For each individual, stature, body weight and sitting height data were collected, their Cormic index and BMI computed, and averages for each district calculated. Mean BMI was found to be lowest for the population of Tikamgarh (17.90+/-1.91 kg m(-2)) and highest for that of Durg district (19.33+/-2.16 kg m(-2)), whereas the mean BMI for the total population of Central India was 18.67+/-2.18 kg m(-2), which is lower than that of well-to-do individuals in India as a whole. The F ratio indicates that there is inter-district variation in anthropometric characteristics of populations. District-wise biosocial indicators were obtained, namely population density per square kilometre, percentage urban population, percentage of population that is of scheduled caste/tribe, sex ratio, average rural population per PHC/CHC (primary or community health centre), literacy rate, life expectancy, total fertility rate, infant mortality rate, gender development index and human development index. Most of these variables were found to be significantly correlated with each other, but BMI was only significantly correlated with three of them, viz. gender development index (R2=0.211), life expectancy (R2=0.130) and infant mortality rate (R2=0.128). Gender development index and life expectancy were positively correlated with BMI, whereas infant mortality rate was negatively correlated. It is concluded that if BMI increases then life expectancy will also increase. Thus better nutritional status may be a helpful tool for reducing infant mortality rate, which is an indicator of socioeconomic status, health condition, health care and ultimately overall development of a region or population. PMID- 17349068 TI - n-3 Fatty acid fortification: opportunities and obstacles. PMID- 17349069 TI - Exploration of possible mechanisms linking vitamin D status and dietary calcium to prostate cancer. PMID- 17349070 TI - On the supposed influence of milk homogenization on the risk of CVD, diabetes and allergy. AB - Commercial milk is homogenized for the purpose of physical stability, thereby reducing fat droplet size and including caseins and some whey proteins at the droplet interface. This seems to result in a better digestibility than untreated milk. Various casein peptides and milk fat globule membrane (MFGM) proteins are reported to present either harmful (e.g. atherogenic) or beneficial bioactivity (e.g. hypotensive, anticarcinogenic and others). Homogenization might enhance either of these effects, but this remains controversial. The effect of homogenization has not been studied regarding the link between early cow's milk consumption and occurrence of type I diabetes in children prone to the disease and no link appears in the general population. Homogenization does not influence milk allergy and intolerance in allergic children and lactose-intolerant or milk hypersensitive adults. The impact of homogenization, as well as heating and other treatments such as cheesemaking processes, on the health properties of milk and dairy products remains to be fully elucidated. PMID- 17349071 TI - Calcium intake and vitamin D metabolism and action, in healthy conditions and in prostate cancer. AB - An association between Ca intake and the risk of prostate cancer has been reported in some but not all epidemiological studies. Assuming that a pathophysiological relationship would underlie this association, a favoured hypothesis proposes that relatively high Ca consumption could promote prostate cancer by reducing the production of 1,25-dihydroxyvitamin D (1,25(OH)2D; calcitriol), the hormonal form of vitamin D. The present review analyses the plausibility of this hypothesis by considering the quantitative relationships linking Ca intake to 1,25(OH)2D production and action in healthy conditions and in prostate cancer. Changes in the plasma level of 1,25(OH)2D in response to Ca intake are of very small magnitude as compared with the variations required to influence the proliferation and differentiation of prostate cancer cells. In most studies, 1,25(OH)2D plasma level was not found to be reduced in patients with prostate cancer. The possibility that the level of 1,25(OH)2D in prostate cells is decreased with a high-Ca diet has not been documented. Furthermore, a recent randomised placebo-controlled trial did not indicate that Ca supplementation increases the relative risk of prostate cancer in men. In conclusion, the existence of a pathophysiological link between relatively high Ca intake and consequent low production and circulation level of 1,25(OH)2D that might promote the development of prostate cancer in men remains so far an hypothesis, the plausibility of which is not supported by the analysis of available clinical data. PMID- 17349072 TI - Oestrogen replacement therapy reduces total plasma homocysteine and enhances genomic DNA methylation in postmenopausal women. AB - Although oestrogen replacement therapy (ERT), which can affect the risk of major cancers, has been known to reduce total plasma homocysteine concentrations in postmenopausal women, the mechanisms and subsequent molecular changes have not yet been defined. To investigate the effect of ERT on homocysteine metabolism, thirteen healthy postmenopausal women were enrolled in a double-blind, placebo controlled, randomized, cross-over study consisting of two 8-week long phases, placebo and conjugated equine oestrogen (CEE; 0.625 mg/d). Concentrations of total plasma homocysteine, vitamin B6 and serum folate and vitamin B12 were measured by conventional methods. Genomic DNA methylation was measured by a new liquid chromatography/MS method and promoter methylation status of the oestrogen receptor (ER)alpha, ERbeta and p16 genes was analysed by methylation-specific PCR after bisulfite treatment. The CEE phase demonstrated a significantly decreased mean of total plasma homocysteine concentrations compared with the placebo phase (8.08 micromol/l (6.82-9.39) v. 9.29 (7.53-11.35), P < 0.05) but there was no difference in the blood concentrations of the three B vitamins. The CEE phase also showed a significantly increased genomic DNA methylation in peripheral mononuclear cells compared with the placebo phase (2.85 (SD 0.12) ng methylcytosine/microg DNA v. 2.40 +/- (SD 0.15) P < 0.05). However, there was no difference in promoter methylation in the ERalpha, ERbeta and p16 genes. This study demonstrates that decreased homocysteinaemia by CEE therapy parallels with increased genomic DNA methylation, suggesting a potential new candidate mechanism by which ERT affects the risk of cancers and a possible new candidate biomarker for the oestrogen-related carcinogenesis through folate-related one-carbon metabolism. PMID- 17349073 TI - The APOB -516C/T polymorphism is associated with differences in insulin sensitivity in healthy males during the consumption of diets with different fat content. AB - Several apo B polymorphic sites have been studied for their potential use as markers for CHD in the population and for potential gene-diet interactions. Our aim was to determine whether the presence of the -516C/T polymorphism in the APOB gene promoter modifies insulin sensitivity to dietary fat. We studied fifty-nine healthy volunteers (thirty men and twenty-nine women, thirty-six homozygotes for the -516C allele (C/C) (nineteen males and seventeen females) and twenty-three heterozygotes for the -516T allele (C/T) (eleven males and twelve females)). Subjects consumed three diets during the feeding study, 4 weeks each: an SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate (CHO)-rich diet (30 % fat, 55 % CHO) or a MUFA-rich diet (38 % fat, 22 % MUFA) following a randomised cross over design. For each diet, we investigated peripheral insulin sensitivity with the insulin suppression test. Male carriers of the -516T allele showed a significantly greater decrease in steady-state plasma glucose concentrations when changing from the SFA-rich diet (9.18 (sd 1.35) mmol/l) to the MUFA (6.55 (sd 0.74) mmol/l) or the CHO (6.31 (sd 0.93) mmol/l) diets than did those who were homozygous for the C allele (P = 0.040). Furthermore, C/T subjects presented higher plasma NEFA values after consumption of the SFA diet compared with the MUFA and CHO diets (P = 0.001). This effect was not observed in females (P = 0.908). Our findings show that male carriers of the -516T allele, C/T, have a significant increase in insulin resistance after consumption of all diets, but the difference is more exaggerated after the SFA diet compared with the MUFA- and CHO-rich diets. PMID- 17349074 TI - Microarray analysis of hepatic genes differentially expressed in the presence of the unsaponifiable fraction of olive oil in apolipoprotein E-deficient mice. AB - The hypothesis that the unsaponifiable fraction of olive oil dramatically influences hepatic gene expression was tested in mice. Two olive oils, obtained from the same olive cultivar but by different technological procedures, were characterized to show that they differed mainly in terms of the composition/quantity of this unsaponifiable fraction. Using DNA microarrays, hepatic gene expression was analysed in apoE-deficient mice fed one of two isoenergetic, isonitrogenous diets containing either 10 % (w/w) olive oil or unsaponifiable fraction-enriched olive oil. To provide an initial screening of potential candidate genes involved in a differential response, only genes with remarkably modified expression (signal log2 ratio >3 or < - 3) were further considered. The eleven genes fulfilling these prerequisites were confirmed by quantitative RT-PCR, and then analysed in apoE-deficient mice with a C57BL/6J genetic background. Orosomucoid and serum amyloid A2 were upregulated (to variable extents depending on the genetic background) in the absence of hepatic steatosis and inflammation. Fabp5 and Mt2 were also strongly upregulated. Several proteases were highly suppressed by the unsaponifiable-enriched olive diet, independent of the genetic background. The findings indicate that change in the expression of these genes is a good marker of the intake of the unsaponifiable fraction of olive oil. The results highlight the important biological effects of the unsaponifiable fraction of olive oil. The term 'monounsaturated fatty acid enriched oil' no longer appears appropriate for describing all the oils to which it is currently applied since it does not adequately reflect that they have different biological effects. PMID- 17349075 TI - Orange juice vs vitamin C: effect on hydrogen peroxide-induced DNA damage in mononuclear blood cells. AB - The intake of fruits rich in vitamin C seems to increase the antioxidant defence of the organism. However, it is still not clear whether vitamin C alone is responsible for this effect. The aim of the present investigation was to study the effect of the intake of a single portion of blood orange juice (BOJ, 300 ml, providing 150 mg vitamin C) on mononuclear blood cell (MNBC) DNA damage, compared with a drink supplemented with the same amount of vitamin C (C-drink) or sugars (S-drink). Seven young healthy subjects were randomised in a repeated-measures design in which they received each drink on different occasions, 2 weeks apart. Blood samples were collected at baseline, every hour for 8 h, and at 24 h after the intake of each drink. Vitamin C was analysed at each time point by HPLC, whereas H2O2-induced MNBC DNA damage was evaluated at 0, 3 and 24 h by means of the comet assay. Plasma vitamin C concentration increased similarly following BOJ or C-drink intake and was not affected by the S-drink. DNA damage significantly decreased 3 h after BOJ intake (about 18 %; P < 0.01) and remained constant at 24 h (about 16 %; P < 0.01). No effect of the C-drink and S-drink was observed. In conclusion, the intake of a single portion of BOJ provided an early protection of MNBC against oxidative DNA damage; however, the protective effect of BOJ was not explained by vitamin C alone, thus other phytochemicals could be involved. PMID- 17349076 TI - Effect of meal composition and cooking duration on the fate of sulforaphane following consumption of broccoli by healthy human subjects. AB - The isothiocyanate, sulforaphane, has been implicated in the cancer-protective effects of brassica vegetables. When broccoli is consumed, sulforaphane is released from hydrolysis of glucoraphanin by plant myrosinase and/or colonic microbiota. The influence of meal composition and broccoli-cooking duration on isothiocyanate uptake was investigated in a designed experiment. Volunteers (n 12) were each offered a meal, with or without beef, together with 150 g lightly cooked broccoli (microwaved 2.0 min) or fully cooked broccoli (microwaved 5.5 min), or a broccoli seed extract. They received 3 g mustard containing pre-formed allyl isothiocyanate (AITC) with each meal. Urinary output of allyl (AMA) and sulforaphane (SFMA) mercapturic acids, the biomarkers of production of AITC and sulforaphane respectively, were measured for 24 h after meal consumption. The estimated yield of sulforaphane in vivo was about 3-fold higher after consumption of lightly cooked broccoli than fully cooked broccoli. Absorption of AITC from mustard was about 1.3-fold higher following consumption of the meat-containing meal compared with the non meat-containing alternative. The meal matrix did not significantly influence the hydrolysis of glucoraphanin and its excretion as SFMA from broccoli. Isothiocyanates may interact with the meal matrix to a greater extent if they are ingested pre-formed rather than after their production from hydrolysis of glucosinolates in vivo. The main influence on the production of isothiocyanates in vivo is the way in which brassica vegetables are cooked, rather than the effect of the meal matrix. PMID- 17349077 TI - Dietary red palm oil reduces ischaemia-reperfusion injury in rats fed a hypercholesterolaemic diet. AB - We have previously shown that dietary red palm oil (RPO) supplementation improves functional recovery in hearts subjected to ischaemia-reperfusion. However, little knowledge exists concerning the effects of RPO supplementation of a high cholesterol diet on ischaemia-reperfusion injury. The signalling mechanisms responsible for RPO's effects in the presence of cholesterol also remain to be elucidated. Therefore, the aim of the present study was to examine the effects of RPO, given with a high-cholesterol diet, on mitogen-activated protein kinase (MAPK) phosphorylation and apoptosis. Long-Evans rats were fed a control diet, a control diet containing 2% cholesterol, or a control diet containing 2% cholesterol and 7 g RPO per kg (CRPO) for 5 weeks. Hearts were excised and mounted on an isolated working heart perfusion apparatus. Cardiac function was measured after which hearts were freeze-clamped and used to assess MAPK phosphorylation and to evaluate apoptosis. Cholesterol supplementation caused a poor aortic output (AO) recovery compared with the control group (35.5 (sem 6.2) v. 55.4 (sem 2.5) %), but when RPO was added, the percentage AO increased significantly. The cholesterol group's poor AO was associated with a significant increase in p38-MAPK phosphorylation, whereas the CRPO-supplemented group showed as significant reduction in p38-MAPK phosphorylation when compared with the cholesterol-supplemented group. This significant reduction in p38-MAPK was also associated with reduced apoptosis as indicated by significant reductions in caspase-3 and poly(ADP-ribose) polymerase cleavage. PMID- 17349078 TI - Serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin K status, and its relationship to bone health indices in Danish girls. AB - Recent cross-sectional data suggest that better vitamin K status in young girls (aged 3-16 years) is associated with decreased bone turnover, even though it is not associated with bone mineral content (BMC). The objective of the present study was to investigate the relationship between serum percentage of undercarboxylated osteocalcin (%ucOC), as an index of vitamin K status, and BMC and biochemical indices of bone turnover in peri-pubertal Danish girls. This peri pubertal stage is a dynamic period of bone development, and as such, may represent an important window of opportunity for vitamin K status to modulate childhood bone health. Serum %ucOC and serum 25-hydroxyvitamin D (25 (OH) D) were measured at baseline in a study of 223 healthy girls aged 11-12 years. Urinary pyridinium crosslinks of collagen and serum total osteocalcin as markers of bone resorption and formation, respectively, as well as BMC (total body and lumbar spine) were also measured. Serum %ucOC (median 21.9 %) was not associated with markers of bone resorption or with total osteocalcin. Serum %ucOC was inversely correlated with serum 25 (OH) D (r - 0.143; P < 0.05). Serum %ucOC was negatively associated with BMC of the total body (beta - 0.045; P < 0.001) and lumbar spine (beta - 0.055; P < 0.05), after adjustment for potential confounders including vitamin D status. Better vitamin K status was associated with increased BMC, but not bone turnover, in healthy peri-pubertal Danish girls. There is a need for well-designed, randomized phylloquinone supplementation trials in children and adolescents to confirm epidemiological findings of an association between vitamin K status and bone health. PMID- 17349079 TI - Whole body and muscle energy metabolism in preruminant calves: effects of nutrient synchrony and physical activity. AB - The effects of asynchronous availability of amino acids and glucose on muscle composition and enzyme activities in skeletal muscle were studied in preruminant calves. It was hypothesized that decreased oxidative enzyme activities in muscle would explain a decreased whole body heat production with decreasing nutrient synchrony. Preruminant calves were assigned to one of six degrees of nutrient synchrony, step-wise separating the intake of protein and lactose over the two daily meals. Calves at the most synchronous treatment received two identical meals daily. At the most asynchronous treatment, 85% of the daily protein and 20% of the daily lactose supply were fed in one meal and the remainder in the other meal. Daily intakes of all dietary ingredients were identical for all treatments. Oxidative enzyme activities and fat content increased with decreasing nutrient synchrony in M. Rectus Abdominis (RA), but not in M. Semitendinosus. Cytochrome-c oxidase activity was positively correlated with fat content in RA (r 0.49; P < 0.01). Oxidative enzyme activities in both muscles were not correlated with average daily heat production, but citrate synthase activity in RA was positively correlated (P < 0.01) with the circadian amplitude (r 0.53) and maximum (r 0.61) of heat production associated with physical activity. In conclusion, this study indicates that muscle energy stores are regulated by nutrient synchrony. The lack of correlation between muscle oxidative enzyme activities and average daily heat production was in contrast with findings in human subjects. Therefore, oxidative enzyme activity in muscle should not be used as an indicator for whole body heat production in growing calves. PMID- 17349080 TI - Consumption of prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis has minor effects on selected immune parameters in polypectomised and colon cancer patients. AB - Probiotics (PRO) modulate immunity in humans, while the effect of prebiotics (PRE) and synbiotics (SYN) on the human immune system are not well studied yet. The objective of this study was to investigate whether daily intake of a SYN modulates immune functions. In a randomised double-blind, placebo-controlled trial, thirty-four colon cancer patients who had undergone 'curative resection' and forty polypectomised patients participated. Subjects of the SYN group daily received encapsulated bacteria (1 x 10(10) colony-forming units of Lactobacillus rhamnosus GG (LGG) and 1 x 10(10) colony-forming units of Bifidobacterium lactis Bb12 (Bb12)) and 10 g of inulin enriched with oligofructose. Controls received encapsulated maltodextrin and 10 g of maltodextrin. Prior to intervention (T1), and 6 (T2) and 12 weeks after the start of the intervention (T3), phagocytic and respiratory burst activity of neutrophils and monocytes, lytic activity of natural killer cells and production of interleukin (IL)-2, IL-10 and IL-12, as well as tumour necrosis factor-alpha and interferon-gamma (IFN-gamma) by activated peripheral blood mononuclear cells (PBMC) were measured. In faeces, the concentrations of transforming growth factor-beta1 and prostaglandin E2 were measured. IL-2 secretion by activated PBMC from the polyp group increased significantly between T1 or T2 and T3 (P < 0.05). In the cancer group, SYN treatment resulted in an increased capacity of PBMC to produce IFN-gamma at T3 (P < 0.05). Other immunity-related parameters were not affected by SYN treatment, neither in the cancer nor in the polyp group. In conclusion, supplementation with this SYN has minor stimulatory effects on the systemic immune system of the two study groups. Further studies in humans should aim to focus on the gut-associated immune system. PMID- 17349081 TI - Effect of dietary fish oil supplementation on cellular adhesion molecule expression and tissue myeloperoxidase activity in diabetic mice with sepsis. AB - This study investigated the effect of n-3 fatty acids on adhesion molecules and tissue myeloperoxidase (MPO) activity in diabetic mice with sepsis. Diabetes was induced by a streptozotocin injection. Mice with blood glucose levels exceeding 2000 mg/l were considered diabetic. Diabetic mice were assigned to two groups with a medium-fat (10 %, w/w) diet either provided by soyabean oil (SO, n 30) or fish oil (FO, n 30). n-3 fatty acids provided 4.3 % of the total energy and the n 3/n-6 fatty acid ratio was 1:2 in the FO diet. After feeding the respective diet for 3 weeks, all mice had sepsis induced by caecal ligation and puncture (CLP) and were killed at 0, 6 or 24 h after CLP, with ten mice at each time-point. The result showed that compared with the SO group, FO group had lower PGE2 and TNF alpha levels in peritoneal lavage fluid after CLP. Lymphocyte CD11a/CD18 expressions were higher at 6 h, whereas the percentage was lower at 24 h in the SO group than in the FO group. Neutrophil CD11b/CD18 expressions were significantly higher in the SO group than in the FO group at 0 h. The FO group had lower organ MPO activities at various time-points after CLP when compared with those of the SO group. The present findings suggest that compared with the diabetic mice fed SO, a low-dose n-3 fatty acid supplementation may attenuate leucocyte adhesion and infiltration into tissues in diabetic mice complicated with sepsis. PMID- 17349082 TI - Ellagic acid inhibits IL-1beta-induced cell adhesion molecule expression in human umbilical vein endothelial cells. AB - Expression of cell adhesion molecules by endothelium and the attachment of monocytes to endothelium may play a major role in atherosclerosis. Ellagic acid (EA) is a phenolic compound found in fruits and nuts including raspberries, strawberries, grapes and walnuts. Previous studies have indicated that EA possesses antioxidant activity in vitro. In the present study, we investigated the effects of EA on the formation of intracellular reactive oxygen species, the translocation of NFkappaB and expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 and endothelial leucocyte adhesion molecule (E-selectin) induced by IL-1beta in human umbilical vein endothelial cells (HUVEC). We found that EA significantly reduced the binding of human monocytic cell line, U937, to IL-1beta-treated HUVEC. The production of reactive oxygen species by IL-1beta was dose-dependently suppressed by EA. Supplementation with increasing doses of EA up to 50 micromol/l was most effective in inhibiting the expression of VCAM-1 and E-selectin. Furthermore, the inhibition of IL-1beta induced adhesion molecule expression by EA was manifested by the suppression of nuclear translocation of p65 and p50. In conclusion, EA inhibits IL-1beta-induced nuclear translocation of p65 and p50, thereby suppressing the expression of VCAM 1 and E-selectin, resulting in decreased monocyte adhesion. Thus, EA has anti inflammatory properties and may play an important role in the prevention of atherosclerosis. PMID- 17349083 TI - Effects of dietary soyabean meal, inulin and oxytetracycline on intestinal microbiota and epithelial cell stress, apoptosis and proliferation in the teleost Atlantic salmon (Salmo salar L.). AB - Soyabean meal (SBM)-induced enteritis in the distal intestine of the teleost Atlantic salmon (Salmo salar L.) and other salmonids may be considered a model for diet-related mucosal disorders in other animals and man. The role of the intestinal microbiota in its pathogenesis was explored. Compared to diets containing fishmeal (FM) as the sole protein source, responses to extracted SBM or the prebiotic inulin, with or without oxytetracycline (OTC) inclusion, were studied following a 3-week feeding trial. Intestinal microbiota, organosomatic indices and histology, as well as immunohistochemical detection of proliferating cell nuclear antigen (PCNA), heat shock protein 70 (HSP70) and caspase-3-positive cells in the distal intestine, were studied. Distal intestine somatic indices (DISI) were higher in inulin and lower in SBM compared to FM-fed fish. The low DISI caused by SBM corresponded with histological changes, neither of which was affected by OTC, despite a significant decrease in adherent bacteria count. Image analysis of PCNA-stained sections showed a significant increase in the proliferative compartment length in SBM-fed fish, accompanied by apparent increases in reactivity to HSP70 and caspase-3 along the mucosal folds, indicating induction of cellular repair and apoptosis, respectively. Fish fed the SBM diet had higher total number as well as a more diverse population composition of adherent bacteria in the distal intestine. Thus SBM-induced enteritis is accompanied by induction of distal intestinal epithelial cell protective responses and changes in microbiota. Putative involvement of bacteria in the inflammatory response merits further investigation. PMID- 17349084 TI - Survival and metabolic activity of selected strains of Propionibacterium freudenreichii in the gastrointestinal tract of human microbiota-associated rats. AB - In addition to their use in cheese technology, dairy propionibacteria have been identified as potential probiotics. However, to have a probiotic effect, propionibacteria have to survive and to remain metabolically active in the digestive tract. The aim of the present study was to investigate the survival and metabolic activity of Propionibacterium freudenreichii within the gastrointestinal tract of human microbiota-associated rats, and its influence on intestinal microbiota composition and metabolism. Twenty-five dairy Propionibacterium strains were screened for their tolerance towards digestive stresses and their ability to produce propionate in a medium mimicking the content of the human colon. Three strains were selected and a daily dose of 2 x 10(10) colony-forming units was fed to groups of human microbiota-associated rats for 20 d before microbiological, biochemical and molecular investigations being carried out. These strains all reached 8-log values per g faeces, showing their ability to survive in the gastrointestinal tract. Transcriptional activity within the intestine was demonstrated by the presence of P. freudenreichii-specific transcarboxylase mRNA. The probiotic efficacy of propionibacteria was yet species and strain-dependent. Indeed, two of the strains, namely TL133 and TL1348, altered the faecal microbiota composition, TL133 also increasing the caecal concentration of acetate, propionate and butyrate, while the third strain, TL3, did not have similar effects. Such alterations may have an impact on gut health and will thus be taken into consideration for further in vivo investigations on probiotic potentialities of P. freudenreichii. PMID- 17349085 TI - Isolation and characterisation of new putative probiotic bacteria from human colonic flora. AB - The present study describes a novel bacterial isolate exhibiting high ability to synthesise and secrete butyrate. The novel isolated bacterium was obtained from human faeces and grown in selective liquid intestinal microflora medium containing rumen fluid under microaerobic conditions. Its probiotic properties were demonstrated by the ability of the isolate to survive high acidity and medium containing bile acids and the ability to adhere to colon cancer cells (Caco-2) in vitro. Phylogenetic identity to Enterococcus durans was established using specific primers for 16S rRNA (99% probability). PCR analyses with primers to the bacterial gene encoding butyrate kinase, present in the butyrogenic bacteria Clostridium, showed that this gene is present in E. durans. The in vivo immunoprotective and anti-inflammatory effects of E. durans were assessed in dextran sodium sulfate (DSS)-induced colitis in Balb/c mice. Administration of E. durans ameliorated histological, clinical and biochemical scores directly related to intestinal inflammation whereas the lactic acid bacterium Lactobacillus delbrueckii was ineffective in this regard. Colonic cDNA concentrations of IL 1beta and TNF-alpha were significantly down regulated in DSS-treated E. durans fed mice but not in control or DSS-treated L. delbrueckii- fed mice. Fluorescent in situ hybridisation analyses of colonic tissue from mice fed E. durans, using a butyrate kinase probe, demonstrated that E. durans significantly adheres to the colonic tissue. The novel isolated bacterium described in the present paper, upon further characterisation, can be developed into a useful probiotic aimed at the treatment of patients suffering from ulcerative colitis. PMID- 17349086 TI - Influence of organic diet on the amount of conjugated linoleic acids in breast milk of lactating women in the Netherlands. AB - The aim of the present study was to find out whether the incorporation of organic dairy and meat products in the maternal diet affects the contents of the conjugated linoleic acid isomers (CLA) and trans-vaccenic acid (TVA) in human breast milk. To this purpose, milk samples from 312 breastfeeding mothers participating in the KOALA Birth Cohort Study have been analysed. The participants had documented varying lifestyles in relation to the use of conventional or organic products. Breast milk samples were collected 1 month postpartum and analysed for fatty acid composition. The content of rumenic acid (the main CLA) increased in a statistically significant way while going from a conventional diet (no organic dairy/meat products, 0.25 weight % (wt%), n 186) to a moderately organic diet (50-90 % organic dairy/meat, 0.29 wt%, n 33, P = 0.02) and to a strict organic diet (>90 % organic dairy/meat, 0.34 wt%, n 37, P 1.6 mmol/l) were enrolled in a 6-month dietary intervention trial conducted in Adelaide (n 47) and Perth (n 39), and randomised to consume control foods or n-3-enriched foods to achieve an EPA + DHA intake of 1 g/d. Test foods were substituted for equivalent foods in their regular diet. Erythrocyte fatty acids, plasma TG and other CVD risk factors were monitored at 0, 3 and 6 months. There were no significant differences between groups for blood pressure, arterial compliance, glucose, insulin, lipids, C-reactive protein (CRP) or urinary 11-dehydro-thromboxane B2 (TXB2) over 6 months, even though regular consumption of n-3-enriched foods increased EPA + DHA intake from 0.2 to 1.0 g/d. However, the n-3 long-chain PUFA content of erythrocytes increased by 35 and 53 % at 3 and 6 months, respectively, in subjects consuming the n-3-enriched foods. These increases were positively associated with measures of arterial compliance and negatively associated with serum CRP and urinary 11-dehydro-TXB2 excretion. Sustainable increases in dietary intakes and erythrocyte levels of n-3 long-chain PUFA can be achieved through regular consumption of suitably enriched processed foods. Such increases may be associated with reduced CV risk. PMID- 17349089 TI - An NMR-based metabonomic investigation on effects of milk and meat protein diets given to 8-year-old boys. AB - The objective of the study was to investigate the ability of an NMR-based metabonomic approach, applied to biofluids, to explore and identify overall exogenous and endogenous biochemical effects of a short-time high intake of milk protein or meat protein given to prepubertal children, the aim being to compare relative differences and not an absolute quantification. A total of twenty-four 8 year-old boys were asked to take 53 g protein as milk (n 12) or meat daily (n 12). At baseline and after 7 d, urine and serum samples were collected and high resolution 1H NMR spectra were acquired on these using a 800 MHz spectrometer. The milk diet reduced the urinary excretion of hippurate, while the meat diet increased the urinary excretion of creatine, histidine and urea. The NMR measurements on serum revealed minor changes in the lipid profile, which most probably should be ascribed to an increase in the content of SCFA in the blood after consumption of the milk diet. The meat diet had no effect on the metabolic profile of serum. The study for the first time demonstrates the capability of proton NMR-based metabonomics to identify the overall biochemical effects of consumption of different animal proteins. The urine metabolite profile is more susceptible to perturbations as a result of short diet interventions than the serum metabolite profile. The milk diet-induced reduction in urinary excretion of hippurate suggests alterations in gut microflora, which may be useful information for further studies elucidating the effects of bioactive components in milk. PMID- 17349090 TI - Vitamin B6 status assessment in relation to dietary intake in high school students aged 16-18 years. AB - The vitamin B6 status of high school students and its relationship with dietary intake were investigated in this cross-sectional study by face-to-face interview. A total of 157 healthy students aged 16-18 years (eighty-three boys and seventy four girls) were randomly recruited from two out of nineteen senior high schools in Tainan, Taiwan. Vitamin B6 intakes were calculated from three 24-h dietary records. Direct and indirect vitamin B6 status indicators were measured in plasma, erythrocytes and urine. The anthropometric data, being similar to those of the first Nutrition and Health Survey in Taiwan (1993-1996), showed the normal growth and development of these students. All students except one girl (28.7 nmol/l) had plasma pyridoxal-5'-phosphate (PLP) levels >35 nmol/l, indicating an adequate vitamin B6 status. The mean dietary vitamin B6 intakes of boys and girls were 1.04 (sd 0.29) and 0.96 (sd 0.27) mg/d, respectively. Vitamin B6 status indicators, including plasma PLP, erythrocyte alanine aminotransferase activity coefficient (EALT-AC), aspartate aminotransferase activity coefficient (EAST-AC) and urinary 4-pyridoxic acid (4-PA), were correlated with vitamin B6 intake. Students with adequate values of plasma PLP (>35 nmol/l), EALT-AC ( < 1.25), EAST AC ( < 1.8) and urinary 4-PA (>3.0 micromol/d) had median intakes of 1.08 and 1.01 mg/d, respectively, for boys and girls. This study suggests that vitamin B6 requirements for boys and girls aged 16-18 years were approximately 1.1 and 1.0 mg/d, respectively. PMID- 17349091 TI - Antidiabetic effect of long-term supplementation with Siraitia grosvenori on the spontaneously diabetic Goto-Kakizaki rat. AB - Siraitia grosvenori Swingle (SG) is a traditional Chinese fruit used as a folk medicine. Its extract (SG-ex) contains potent sweet elements with a sweetness several hundred times higher than table sugar. We investigated the antidiabetic effect of SG-ex in the type 2 diabetic Goto-Kakizaki (GK) rat. Diabetic 7-week old GK rats were fed a diet supplemented with 0.4 % of the SG-ex for 13 weeks, and its antidiabetic effects were evaluated. SG-ex had no effect on food intake or body weight. In oral glucose tolerance tests (OGTT), SG-ex supplementation improved the insulin response at 15 min (control, 63 (sem 6) pm; SG-ex, 107 (sem 20) pm; P < 0.05) and reduced the plasma glucose level at 120 min after the glucose administration (control, 18.5 (sem 0.8) mm; SG-ex, 14.8 (sem 0.7) mm; P < 0.05). The total amount of insulin in whole pancreas taken from fasting rats was higher in the SG-ex-supplemented group, which may explain the greater capacity to secrete insulin during the OGTT. Thiobarbituric acid-reactive substances in both the liver and the plasma were lower in the SG-ex-supplemented group, suggesting that an absorbable component in SG-ex has an antioxidative effect on lipid peroxidation, thereby counteracting the oxidative stress caused by a diabetic state. Excreted urine volume and urinary albumin level for 24 h were both reduced in the SG-ex-supplemented group, suggesting the attenuation of kidney damage that is caused by diabetes. These data indicate that SG-ex supplementation may prevent complications and attenuate pathological conditions for type 2 diabetes, along with its sweet characteristics. PMID- 17349092 TI - Effects of fructans-containing yacon (Smallanthus sonchifolius Poepp and Endl.) flour on caecum mucosal morphometry, calcium and magnesium balance, and bone calcium retention in growing rats. AB - Yacon roots have been considered a functional food due to the high levels of fructans they contains. In the present study, Ca and Mg balance, bone mass and strength, and caecum mucosal morphometry were evaluated. Growing male Wistar rats (n 24) were fed ad libitum control diets or diets supplemented with yacon flour (5 or 7.5 % fructooligosaccharides) for 27 d. Mineral balance was evaluated in three periods of 5 d (starting on the 4th, 10th and 16th days). After the rats were killled, the bones were removed and bone mineral density was measured. Ca analyses were performed on left femurs and tibias and biomechanical testing on right femurs. The caecum was removed and tissue samples were collected for histological analysis. Caecal histology changed noticeably in rats fed yacon flour: there was an increase in the depth and number of total and bifurcated crypts as well. Yacon flour consumption significantly (P < 0.05) resulted in a positive Ca and Mg balance, leading to higher values of bone mineral retention and biomechanical properties (peak load and stiffness) when compared to the control group. The positive effects on mineral intestinal absorption, bone mass and biomechanical properties showed an important role of yacon roots in the maintenance of healthy bones. The increased number of bifurcating crypts might be related to the higher mineral absorption caused by the enlargement of the absorbing surface in the large intestine of the animals. PMID- 17349093 TI - Attenuation of stress-induced anorexia in brown trout (Salmo trutta) by pre treatment with dietary l-tryptophan. AB - The general consensus is that brain serotonin (5-HT) inhibits feed intake in teleost fishes and other vertebrates. Dietary manipulations with the 5-HT precursor tryptophan (TRP) have, however, yielded contradictory effects on feed intake, while studies of the endocrine response to stress indicate that the effects of TRP-enriched feed are context dependent. A characteristic behavioural response to stress is a reduction in feed intake, and in the present study we investigated whether pre-treatment with TRP-enriched feed affected stress-induced changes in feeding behaviour in brown trout (Salmo trutta). After acclimatisation in observation aquaria, isolated fish were fed control or TRP-supplemented feed for 7 d, whereupon they were transferred to a novel environment, in which all fish were fed control feed. Transfer to a new environment resulted in decreased feeding in both the TRP pre-treated and the control-treated group. However, this decrease was more pronounced in the control-treated group. Previous experiments have concluded that stimulation of brain 5-HT systems by TRP enhancement does not affect feed intake in salmonid fishes, but in these studies food intake was observed in unstressed animals only. The present study suggests that pre treatment with dietary TRP attenuates stress-induced anorexia. Hence, it appears that the effect of dietary manipulations of TRP on feeding behaviour is dependent on the stress levels experienced by experimental animals. These behavioural data are discussed in the context of the involvement of 5-HT in appetite regulation. PMID- 17349094 TI - Motivational effects of 12-week moderately restrictive diets with or without special attention to the Glycaemic Index of foods. AB - Low glycaemic index (GI) diets may facilitate weight loss via behavioural and/or endocrine mechanisms. This study investigated whether the outcomes of the Weight Watchers POINTS Weight-Loss System could be improved by encouraging dieters to select low GI, high-carbohydrate foods. Ninety-six women (age 20-72 years; BMI 25 40 kg/m2) were recruited as they started the Weight Watchers POINTS programme for 12 weeks. Weekly classes were randomized so that seven (forty-five women) followed the regular programme while seven others (fifty-one women) followed a revised programme encouraging the selection of low GI foods. Anthropometric and biochemical parameters were measured before and after the 12-week diets. Participants rated hunger and desire to eat using visual analogue scales on 1 d per week, several times per d. Attrition was the same in both groups (32 v. 30 %), as well as many benefits (5 % weight loss, decreases in insulinaemia and blood lipids, waist and hip circumferences, blood pressure). Hunger and desire to eat were rated consistently lower in the low GI group over the 12-week diet. Group differences in subjective sensations were especially large in the afternoon. The 12-week weight management yielded many significant anthropometric and biochemical benefits that were not improved by encouraging dieters to select low GI foods. The subjective benefits (lower hunger and desire to eat) of the low GI diet may be a worthwhile contribution to the motivation of dieters that might affect adherence to the diet over the long term. PMID- 17349095 TI - Central adiposity in Brazilian schoolchildren aged 7-10 years. AB - Waist circumference (WC) is a measure of central adiposity related to elevated risk factor levels in children and adolescents. The aim of the present study was to describe WC percentiles in 7- to 10-year-old Brazilian children and to compare frequencies of obesity and overweight as defined by BMI and frequencies of excess and at risk of abdominal adiposity as defined by WC to the corresponding age and sex data from British references. A representative sample of 2919 schoolchildren of the city of Florianopolis (southern Brazil) was examined. Smoothed WC percentiles were derived using the least mean square method. Frequencies of overweight and obesity and of excess and at risk of abdominal adiposity were assessed using the 91st and 98th centiles of the British references as cut-off points. WC increased with age in both boys and girls, with higher values for boys at every age and percentile level. Nutritional status categories of children assessed by the 91st and 98th British BMI and WC centiles showed moderate agreement (weighted kappa = 0.58). Overweight was more frequent in Brazilian than British children: 15.1 % of girls and 20.1 % of boys were above the 91st percentile of the 1990 BMI for age British references. About one-quarter (22.0 % of girls and 26.9 % of boys) exceeded the 91st percentile of WC British references. The present data could be used to compare WC in children in other populations and may serve as a baseline for future studies of temporal trends in WC in Brazil. PMID- 17349096 TI - Outcomes of septal surgery. AB - OBJECTIVE: To assess the change in health-related quality of life following septal surgery. STUDY DESIGN: Post-intervention, health-related quality of life questionnaire. PARTICIPANTS: Adult patients undergoing septal surgery, recruited from two sources (the Scottish ENT outcomes study and the North Glasgow National Health Service Trust) over an 18-month period. MAIN OUTCOME MEASURE: Glasgow benefit inventory score. RESULTS: A total of 149 Glasgow benefit inventories were returned. Of these, 13 were incomplete and were thus excluded, leaving 136 to be analysed. The response rate from the Scottish ENT outcomes study patients was 55 per cent and the response rate from the North Glasgow National Health Service Trust patients was 41 per cent, giving an overall response rate of 49 per cent. The mean Glasgow benefit inventory score was 11.3 (standard deviation 20, 95 per cent confidence interval 7.8 to 14.7). This result was similar to those of other studies using the Glasgow benefit inventory to assess septal surgery outcomes. CONCLUSION: Patients reported minimal improvement in their health-related quality of life following septal surgery. PMID- 17349097 TI - Fibro-osseous lesion of the middle turbinate: ossifying fibroma or fibrous dysplasia? AB - Benign fibro-osseous tumours of the head and neck region seldom appear in the midface and nasal cavity. Correct differential diagnosis of fibro-osseous tumours is crucial for adequate therapy, as their clinical aggressiveness seems to differ. The rather uncommon case of a 14-year-old boy with a tumour of the middle turbinate is presented. The radiologic appearance of the tumour, on computed tomography and magnetic resonance imaging scans, was consistent with fibrous dysplasia. Angiography revealed extensive vascularisation of the tumour from both the internal and external carotid arteries. To avoid ipsilateral blindness following embolisation, a superselective embolisation of the supplying blood vessels was performed. The tumour was completely resected via an endoscopic approach. Histopathology revealed an ossifying fibroma. This case emphasises the importance of interpretation of the clinical, radiological and histological features before planning definitive treatment. Moreover, when fibro-osseous tumours are suspected, the possibility of extensive, complicated vascularisation must be considered. This case underwent radical resection, with no recurrence after four years' follow up. PMID- 17349098 TI - Idiopathic, inflammatory, medial meatal, fibrotising otitis presenting with lichen planus. AB - BACKGROUND: Of the acquired ear canal atresias, idiopathic, inflammatory, medial meatal, fibrotising otitis has been suggested as a distinct disease entity, for reasons of aetiology. OBJECTIVE: To report three more cases of idiopathic, inflammatory, medial meatal, fibrotising otitis and to further consider the possible relationship between this condition and lichen planus. PATIENTS: Three adult patients with idiopathic, inflammatory, medial meatal, fibrotising otitis, two with bilateral aural symptoms, treated and followed up at the department of otorhinolaryngology of Helsinki University Hospital. RESULTS: We found idiopathic, inflammatory, medial meatal, fibrotising otitis, affecting solely the glabrous skin of the osseous part of the external ear canals, in three patients who also suffered from severe oral lichen planus. CONCLUSIONS: The aetiopathology or pathophysiology of idiopathic, inflammatory, medial meatal, fibrotising otitis may be linked with lichen planus. Early, active treatment of idiopathic, inflammatory, medial meatal, fibrotising otitis with local corticosteroids may prevent total medial meatal atresia. PMID- 17349099 TI - Morbidity and mortality of post-tonsillectomy bleeding: analysis of cases. AB - OBJECTIVES: To analyse the circumstances of mortality in post-tonsillectomy bleeding cases, in order to better manage serious problems during resuscitation. DESIGN: Reports of inquiry committees on post-tonsillectomy mortalities. SETTING: State of Israel Ministry of Health committees. PARTICIPANTS: Senior otolaryngologists and related professionals, and the involved medical staff who participated in the inquiry committees. MAIN OUTCOMES MEASURES: Identification of actions causing undesirable effects on resuscitation outcomes. RESULTS: In recent years, the post-tonsillectomy mortality rate in Israel has been one in 12,000. The two main causes of death have been severe haemorrhagic shock and airway obstruction. CONCLUSIONS: Active bleeding should be treated, rather than waiting for spontaneous resolution. An efficient airway should be established early during resuscitation, either by intubation (within two minutes) or by cricothyroidotomy. The two main factors endangering the patient's life during resuscitation are severe blood loss, interfering with effective cardiac output, and airway obstruction. Blood loss should be quickly substituted. PMID- 17349100 TI - Sacculo-collic response in otosclerosis and following successful stapes surgery. AB - INTRODUCTION: The sacculo-collic reflex is believed to be a short latency, otolith-mediated myogenic response to sound. With the application of air conducted sound, one would expect an absent response in stapes fixation, as a fixed stapes footplate will not transmit a pressure wave to the saccule. METHODS: Fifty patients (70 stapes surgery ears, 26 otosclerotic ears and four normal ears) and 40 controls underwent repeated sacculo-collic tests. RESULTS: The results support the proposed mechanism for the sacculo-collic response. The study also suggests that, whilst stapedotomy piston prostheses are effective in the reversal of conductive hearing loss, they produce an insufficient pressure wave to elicit a myogenic response to sound. CONCLUSION: The sacculo-collic test could be a useful tool for screening otolith function and inferior vestibular nerve integrity, but further work is needed to determine the effect of stapes surgery on saccular function. PMID- 17349101 TI - Clinical presentation of postnatal and non-postnatal depressive episodes. AB - BACKGROUND: The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. METHOD: In a sample of well characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. RESULTS: The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. CONCLUSIONS: The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression. PMID- 17349102 TI - Personality diatheses: a superior explanation than disorder. AB - Diatheses confer vulnerability to disorder but are not necessarily manifest overtly or consistently. It is suggested that the main empirical findings of studies with abnormal personality support the notion that they are diatheses rather than disorders. This includes their onset early in life, their variability of expression dependent on setting, their greater association with more severe disorders and their acceptance as intrinsic components of functioning by most suffering from these conditions. It is argued that a separate axis of classification for personality diatheses rather than disorders is justified. PMID- 17349103 TI - Two-phase survey of eating disorders in gifted dance and non-dance high-school students in Taiwan. AB - BACKGROUND: Despite a growing body of literature reporting eating disorders (EDs) in non-Western countries in recent years, most of these studies are limited to questionnaire-based surveys or case-series studies. This study aimed to investigate the prevalence and correlates of EDs in Taiwanese high-school students. METHODS: The study subjects consisted of all the female high-school students enrolled in the gifted dance class in 2003 in Taiwan (n=655) and non dance female students randomly chosen from the same school (n=1251). All the participants were asked to complete self-report questionnaires, including the 26 item Eating Attitudes Test (EAT-26) and the Bulimic Investigatory Test Edinburgh (BITE). All the screen positives and an approximate 10% random sample of the screen negatives were then interviewed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders Patient Version (SCID-I/P). RESULTS: The prevalence of individual EDs was much higher in the dance [0.7% for anorexia nervosa (AN), 2.5% for bulimia nervosa (BN) and 4.8% for EDs, not otherwise specified (EDNOS)] than in the non-dance (0.1, 1.0 and 0.7% respectively) students. Multivariate logistic regression analyses revealed that being in the dance class, higher concern about body shape and lower family support were correlates of EDs for all students, whereas lower parental education level was associated with EDs only for non-dance students. CONCLUSION: EDs were more prevalent in the weight-concerned subpopulation. Although AN is still rare, BN has emerged as a comparable prevalent disorder in Taiwan, as in Western countries. PMID- 17349104 TI - The profile and risks of suicidal behaviours in the Nigerian Survey of Mental Health and Well-Being. AB - BACKGROUND: Suicide is a leading cause of death worldwide but information about it is sparse in Sub-Saharan Africa. Suicide-related behaviours can provide an insight into the extent of this compelling consequence of mental illness. METHOD: Face-to-face interviews were conducted with a representative sample of persons aged 18 years and over (n=6752) in 21 of Nigeria's 36 states (representing about 57% of the national population). Suicide-related outcomes, mental disorders, as well as history of childhood adversities were assessed using the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). RESULTS: Lifetime prevalence estimates of suicide ideation, plan and attempts were 3.2% [95% confidence interval (CI) 1.4-6.5], 1.0% (95% CI 0.4-7.5) and 0.7% (95% CI 0.5-1.0) respectively. Almost two of every three ideators who made a plan went on to make an attempt. The highest risks for transition from ideation to plan and from plan to attempt were in the first year of having ideation or plan respectively. Mental disorders, especially mood disorders, were significant correlates of suicide-related outcomes. Childhood adversities of long separation from biological parents, being raised in a household with much conflict, being physically abused, or being brought up by a woman who had suffered from depression, anxiety disorder, or who had attempted suicide were risk factors for lifetime suicide attempt. CONCLUSIONS: History of childhood adversities and of lifetime mental disorders identify persons at high-risk for suicide-related outcomes. Preventive measures are best delivered within the first year of suicide ideation being expressed. PMID- 17349105 TI - Characteristics and functions of non-suicidal self-injury in a community sample of adolescents. AB - BACKGROUND: Few studies have investigated non-suicidal self-injury (NSSI), or the deliberate, direct destruction of body tissue without conscious suicidal intent, and the motivations for engaging in NSSI among adolescents. This study assessed the prevalence, associated clinical characteristics, and functions of NSSI in a community sample of adolescents. METHOD: A total of 633 adolescents completed anonymous surveys. NSSI was assessed with the Functional Assessment of Self Mutilation (FASM). RESULTS: Some form of NSSI was endorsed by 46.5% (n=293) of the adolescents within the past year, most frequently biting self, cutting/carving skin, hitting self on purpose, and burning skin. Sixty per cent of these, or 28% of the overall sample, endorsed moderate/severe forms of NSSI. Self-injurers reported an average of 12.9 (s.d.=29.4) incidents in the past 12 months, with an average of 2.4 (s.d.=1.7) types of NSSI used. Moderate/severe self-injurers were more likely than minor self-injurers, who in turn were more likely than non-injurers, to have a history of psychiatric treatment, hospitalization and suicide attempt, as well as current suicide ideation. A four factor model of NSSI functions was indicated, with self-injurers likely to endorse both reasons of automatic reinforcement and social reinforcement. The most common reasons for NSSI were 'to try to get a reaction from someone', 'to get control of a situation', and 'to stop bad feelings'. CONCLUSIONS: Community adolescents reported high rates of NSSI, engaged in to influence behaviors of others and to manage internal emotions. Intervention efforts should be tailored to reducing individual issues that contribute to NSSI and building alternative skills for positive coping, communication, stress management, and strong social support. PMID- 17349106 TI - A naturalistic study of the effects of pharmacotherapy on substance use disorders among ADHD adults. AB - BACKGROUND: Studies of adults with attention deficit hyperactivity disorder (ADHD) show an elevated prevalence of substance use disorders (SUDs) and the substance abuse literature shows that ADHD is elevated in substance users. Some researchers postulate that stimulant treatment of ADHD increases the risk for SUD in ADHD patients but follow-up studies suggest treatment protects patients from subsequent SUDs. This report uses retrospective data to assess the impact of prior ADHD pharmacotherapy on SUDs in 206 ADHD adults (n=79 late-onset ADHD, n=127 full ADHD) grouped by lifetime history of ADHD treatment (no treatment, past treatment, current and past treatment). METHOD: Structured Clinical Interview for DSM-IV (SCID) data were used to establish abuse and dependence, and Drug Use Screening Inventory (DUSI) responses were used to establish prevalence of use, preference for cigarettes, alcohol and drugs of abuse, complications from use, and motivation for use (get high, change mood, sleep better). RESULTS: No differences were found in the prevalence of cigarette smoking, alcohol or drug abuse or dependence, as well as no significant differences in 1-month prevalence of any use or use more than 20 times. No differences were found in complications of drug or alcohol use across groups. Subjects with current treatment rated getting high as a motivating factor significantly more frequently than subjects in the past treatment group; this result lost significance when we included ADHD diagnostic category. CONCLUSIONS: Our results are consistent across substances and ADHD diagnoses, and support the hypothesis that pharmacotherapy does not cause subsequent SUDs. PMID- 17349107 TI - Suicide and other causes of mortality in bipolar disorder: a longitudinal study. AB - BACKGROUND: The high risk of suicide in bipolar disorder is well recognized, but may have been overestimated. There is conflicting evidence about deaths from other causes and little known about risk factors for suicide. We aimed to estimate suicide and mortality rates in a cohort of bipolar patients and to identify risk factors for suicide. METHOD: All patients who presented for the first time with a DSM-IV diagnosis of bipolar I disorder in a defined area of southeast London over a 35-year period (1965-1999) were identified. Mortality rates were compared with those of the 1991 England and Wales population, indirectly standardized for age and gender. Univariate and multivariate analyses were used to test potential risk factors for suicide. RESULTS: Of the 239 patients in the cohort, 235 (98.3%) were traced. Forty-two died during the 4422 person-years of follow-up, eight from suicide. The standardized mortality ratio (SMR) for suicide was 9.77 [95% confidence interval (CI) 4.22-19.24], which, although significantly elevated compared to the general population, represented a lower case fatality than expected from previous literature. Deaths from all other causes were not excessive for the age groups studied in this cohort. Alcohol abuse [hazard ratio (HR) 6.81, 95% CI 1.69-27.36, p=0.007] and deterioration from pre-morbid level of functioning up to a year after onset (HR 5.20, 95% CI 1.24 21.89, p=0.024) were associated with increased risk of suicide. CONCLUSIONS: Suicide is significantly increased in unselected bipolar patients but actual case fatality is not as high as previously claimed. A history of alcohol abuse and deterioration in function predict suicide in bipolar disorder. PMID- 17349108 TI - Hyperbaric exposure with high oxygen concentration improves altered fiber types in the plantaris muscle of diabetic Goto-Kakizaki rats. AB - Hyperbaric exposure with high oxygen concentration inhibits a growth-related increase in the glucose and insulin of diabetic rats. In this study, 5-week-old diabetic Goto-Kakizaki rats were exposed to a hyperbaric environment (1.25 atmospheric pressure) with a high oxygen concentration (36%) for 6 h daily. Fiber type distributions and oxidative enzyme activities in the fast-twitch plantaris muscle of Goto-Kakizaki rats were examined after hyperbaric exposure for 4 weeks. The percentages of high-oxidative type I and type IIA fibers increased and that of low-oxidative type IIB fibers decreased after hyperbaric exposure. Furthermore, the fiber oxidative enzyme activity increased after hyperbaric exposure, regardless of fiber type. It is concluded that altered patterns of fiber types in the plantaris muscle of diabetic rats shift toward normal, which is observed in nondiabetic rats, following hyperbaric exposure with high oxygen concentration. PMID- 17349109 TI - Parasitism of Greenbug, Schizaphis graminum, by the parasitoid Lysiphlebus testaceipes at winter temperatures. AB - Functional responses by Lysiphlebus testaceipes (Cresson), a common parasitoid of small grain aphids, on greenbug, Schizaphis graminum (Rondani), were measured at seven temperatures (14, 12, 10, 8, 6, 4, and 2 degrees C) during a 24-h period (12-h light: 12-h dark). Oviposition by L. testaceipes ceased at temperatures <4 degrees C. At all experimental temperatures, a type I, rather than a type II or type III, functional response was determined to be the best fit based on coefficient of determination (r2) values. L. testaceipes was observed to oviposit in greenbugs at temperatures below the developmental temperature of both the greenbug host (5.8 degrees C) and the parasitoid itself (6.6 degrees C). This ability to oviposit at subdevelopmental temperatures enables the parasitoid to increase the percentage of greenbugs that are parasitized while the greenbugs are unable to reproduce. The implications of these findings regarding population suppression of greenbugs are discussed. PMID- 17349110 TI - Development of Iphiseiodes quadripilis (Banks) (Acari: Phytoseiidae) on pollen or mite diets and predation on Aculops pelekassi (Keifer) (Acari: Eriophyidae) in the laboratory. AB - Development and reproduction of Iphiseiodes quadripilis (Banks) were evaluated on single food diets of pollen (Malephora crocea Jacquin [ice plant] or Quercus sp. [oak]), spider mites, [Eutetranychus banksi (McGregor) or Panonychus citri (McGregor) (Acari: Tetranychidae)], or the citrus rust mite Phyllocoptruta oleivora (Ashmead) (Acari: Eriophyidae). Experiments were conducted in an environmental chamber at 28 degrees +/- 1 degrees C, 14:10 (L:D) daylength, and 45% RH. I. quadripilis completed development and laid viable eggs that subsequently hatched on diets of either ice plant or oak pollen or eggs and motile stages of E. banksi. P. citri was acceptable as prey, but survival of larvae to adults was only 36%, whereas survival on E. banksi, ice plant pollen, and oak pollen was 48, 60, and 68%, respectively. The webbing produced by P. citri seemed to inhibit foraging behavior of I. quadripilis larvae and nymphs. Larvae of I. quadripilis developed only to the second nymphal instar on a diet of P. oleivora alone or water alone. Starved I. quadripilis females and deutonymphs were observed preying on the pink citrus rust mite, Aculops pelekassi (Keifer) (Eriophyidae). During 4-min observation trials, two series of I. quadripilis fed on 1.8 +/- 0.47 and 3.5 +/- 0.45 A. pelekassi motile stages after being starved for 6 and 24 h, respectively. I. quadripilis females did not prey on P. oleivora in arenas containing both rust mite species. PMID- 17349111 TI - Seasonal timing of diapause induction limits the effective range of Diorhabda elongata deserticola (Coleoptera: Chrysomelidae) as a biological control agent for tamarisk (Tamarix spp.). AB - The leaf beetle Diorhabda elongata Brulle subspecies deserticola Chen, collected in northwestern China, has been released in the western United States to control tamarisk (Tamarix spp.). While beetle establishment and saltcedar defoliation have been noted at northern study sites, this species has not established at latitudes south of the 38th parallel. Critical daylength for diapause induction was measured in the laboratory and ranged between 14 h 50 min to 15 h 08 min, depending on temperature, and adults were shown to cease reproduction and enter diapause at daylengths of 14 h 30 min or less. Critical daylength in the field was measured at approximately 14 h 39 min and occurred 13 d before 50% of the population reached diapause. South of 36 degrees 20' N, the longest days of the year are shorter than 14 h 39 min, making the beetles univoltine in the southern United States. North of 36 degrees 20' N, a window of reproductive activity opens 13 d after the critical daylength is reached in the spring and closes 13 d after it is passed in the summer, allowing at least a partial second summer generation. It is predicted that south of the 38th parallel, premature diapause will increase mortality and disrupt synchrony between the life cycle of the beetle and host plant availability. This could hinder establishment and help explain the failure of this population south of the 38th parallel, providing a rationale for testing other populations of D. elongata in the southern range of Tamarix in North America. PMID- 17349112 TI - Soil potassium deficiency affects soybean phloem nitrogen and soybean aphid populations. AB - The soybean aphid is an invasive pest in the midwest United States, with frequent population outbreaks. Previous work has shown that aphid population densities are higher on potassium-deficient soybean than on healthy soybean. The experiments reported here test the hypotheses that the potassium nutrition of the host plant affects the forms of phloem nitrogen available to soybean aphids, and subsequently, their abundance. In field surveys and an exclusion cage study when aphid populations were high, soybean plants with potassium deficiency symptoms had a higher density of soybean aphids than plants without deficiency symptoms. In clip cage experiments, this effect was caused by earlier aphid reproduction and higher numbers of aphid nymphs per mother on plants growing in lower potassium soil. In phloem exudation samples, the percentage of asparagine, an important amino acid for aphid nutrition, increased with decreasing soil potassium, perhaps because of potassium's role in the nitrogen use of the plant. Taken together, these results show that soybean potassium deficiency can lead to higher populations of soybean aphid through a bottom-up effect. A possible mechanism for this relationship is that soybean potassium deficiency improves the nitrogen nutrition of these N-limited insects. By releasing these herbivores from N limitation, host plant potassium deficiency may allow soybean aphid populations to reach higher levels more rapidly in the field. PMID- 17349113 TI - Development of Spalangia cameroni and Muscidifurax raptor (Hymenoptera: Pteromalidae) on live house fly (Diptera: Muscidae) pupae and pupae killed by heat shock, irradiation, and cold. AB - The objective of this study was to evaluate the suitability of killed house fly (Musca domestica L) pupae for production of two economically important pupal parasitoids. Two-day-old fly pupae were subjected to heat shock treatments of varying temperatures and durations in an oven at >or=70% RH; exposure to temperatures of 55 degrees C or higher for 15 min or longer resulted in 100% mortality. Exposure to 50 degrees C resulted in 40 and 91% mortality at 15 and 60 min, respectively. All (100%) pupae placed in a -80 degrees C freezer were killed after 10-min exposure; exposure times of <5 min resulted in <21% mortality. Progeny production of Spalangia cameroni Perkins and Muscidifurax raptor Girault and Sanders (Hymeoptera: Pteromalidae) from pupae killed by heat shock or 50 kR of gamma radiation was not significantly different from production on live hosts on the day when pupae were killed. Freeze-killed pupae produced 16% fewer S. cameroni than live pupae and an equivalent amount of M. raptor progeny on the day when pupae were killed. When killed pupae were stored in freezer bags at 4 degrees C for 4 mo, heat-killed, irradiated, and freeze-killed pupae remained as effective for production of M. raptor as live pupae. Production of S. cameroni on heat-killed and irradiated pupae was equal to parasitoid production on live pupae for up to 2 mo of storage, after which production on killed pupae declined to 63% of that observed with live pupae. Production of S. cameroni on freeze-killed pupae was 73-78% of production using live pupae during weeks 2-8 of storage and declined to 41 and 28% after 3 and 4 mo, respectively. Killing pupae by heat shock provides a simple and low-cost method for stockpiling high-quality hosts for mass-rearing both of these filth fly biological control agents. PMID- 17349114 TI - Effects of temperature on the immature development of the stone leek leafminer Liriomyza chinensis (Diptera: Agromyzidae). AB - The effect of nine constant temperatures (15, 17.5, 20, 22.5, 25, 27.5 30, 32.5, and 35 degrees C) on the development of the stone leek leafminer, Liriomyza chinensis (Kato), on Japanese bunching onion, Allium fistulosum L., was studied in the laboratory. Developmental times for immature stages were inversely proportional to temperature between 15 and 30 degrees C but increased at 32.5 degrees C. Total developmental times from egg to adult emergence decreased from 69.6 to 17.1 d for temperatures from 15 to 30 degrees C, with pupae requiring more time for development than the combined egg and larva stages. Both linear and nonlinear (Logan equation VI) models provided a reliable fit of development rates versus temperature for all immature stages. The lower developmental thresholds that were estimated from linear regression equations for the egg, first, second, and third instars, total larva, egg-larval, pupa, and total combined immature stages were 12.1, 10.6, 13.6, 8, 9.6, 11.3, 11.2, and 11.4 degrees C, respectively. The degree-day accumulation was calculated as 312.5 DD for development from egg to adult emergence. By fitting the nonlinear models to the data, the upper and optimal temperatures for egg, larva, pupa, and total immature stages were calculated as 37.8 and 31.7, 34.9 and 30.1, 35.8 and 30.6, and 35.0 and 30.9 degrees C, respectively. These data are useful for predicting population dynamics of L. chinensis under field conditions and determining the maximum proportion of susceptible individuals for facilitating improved timing of application of control measures. PMID- 17349115 TI - Biology of Pentalonia nigronervosa (Hemiptera, Aphididae) on banana using different rearing methods. AB - The banana aphid, Pentalonia nigronervosa Coquerel, is present worldwide where banana (Musa spp.) is grown. It is the vector of Banana bunchy top virus (Nanoviridae, Babuvirus), the etiological agent of banana bunchy top disease, currently the most important constraint for banana producers in Hawaii. P. nigronervosa is not well studied, and effects of temperature on its growth and reproduction are unknown. We studied the longevity and fecundity of one clone of banana aphid on different types of plant materials to determine an effective method to study the insect in the laboratory. We found that insects performed better unconfined on plantlets, followed by leaf midrib cuttings. We also conducted complete life table studies with P. nigronervosa on banana leaf midrib cuttings at 20, 25, and 30 degrees C, with a photoperiod of 12:12. Intrinsic rate of increase (r), net reproductive rate (R0), doubling time (DT), nymphal mortality, and mean offspring per female all showed maximal rates at 25 degrees C. Population growth was studied on whole banana plantlets as well, and growth rates were also highest at 25 degrees C. We found r to be greater when aphids were reared on intact banana plantlets than on cuttings. Our results show the importance of comparing insect rearing methods for studies such as life tables. PMID- 17349116 TI - Aggregation pheromone of Metamasius spinolae (Coleoptera: Curculionidae): chemical analysis and field test. AB - Male Metamasius spinolae (Gylh.) produce several volatile compounds that are likely constituents of its aggregation pheromone. These compounds were identified by volatile collections and gas chromatography (GC), followed by coupled gas chromatography-mass spectrometry (GC-MS), as 2-methyl-4-heptanone [1], 6-methyl 2hepten-4-one [2], and 2-hydroxy-2-methyl-4-heptanone [3]. Preliminary field experiments using synthetic racemates of these compounds showed that significantly more adult cactus weevils were caught in traps baited with the major single compound three or the 2 + 3 binary combination than in unbaited control traps. However, highest trap efficacy occurred with the 1 + 2 binary combination and a blend of all three synthetic compounds plus prickly pear. Potential uses for the cactus weevil pheromone and possible ways to increase trap captures are discussed. PMID- 17349117 TI - Role of host volatiles in mate location by the Japanese pine sawyer, Monochamus alternatus hope (Coleoptera: Cerambycidae). AB - We evaluated the responses of male and female Monochamus alternatus Hope (Coleoptera: Cerambycidae) to various terpenes commonly associated with host trees. Electroantennogram (EAG) tests were conducted with 12 plant volatile compounds and ethanol. Antennae of both sexes were highly sensitive to (R)-(+) alpha-pinene, (+)-3-carene, (-)-beta-pinene, and terpinolene. Both sexes of M. alternatus were attracted by traps baited with (+)-alpha-pinene, (-)-beta-pinene, (+)-3-carene, or terpinolene. Our results support the first of the three-stage hypothesis posed by Ginzel and Hanks that suggests that location of stressed trees by cerambycids involves three stages: (1) both sexes locate larval hosts by using plant volatiles as kairomones; (2) males produces sex pheromones to attract females after both sexes land on the larval hosts; (3) males and female recognize each other by contract pheromones in their epicuticular wax layer. Males and females showed differences in their EAG responses to several compounds, including (R)-(+)-alpha-pinene, (-)-beta-pinene, myrcene, (+)-3-carene, (R)-(+)-limonene, terpinolene, and trans-caryophyllene. In all cases, males exhibited greater sensitivity than females. In laboratory assays, male M. alternatus showed strong preference for 1% (+)-alpha-pinene and 1% (-)-beta-pinene over other compounds. In field assays, traps baited with (+)-alpha-pinene, (-)-beta-pinene, (+)-3 carene, or terpinolene caught more beetles than control traps. We found strong male bias in beetle catches in baited traps and those captured on the stem of stressed trees despite a strong female bias in emerging beetles in 2004. We hypothesize that male M. alternatus are more responsive than females to plant volatiles and that males have more capacity than females in finding mating locations. PMID- 17349118 TI - Temporal variation in mycophagy and prevalence of fungi associated with developmental stages of Dendroctonus ponderosae (Coleoptera: Curculionidae). AB - Mycophagy by bark beetles is widespread. However, little is known regarding which developmental stages of bark beetles actually feed on fungi. To study this question, we sampled fungi associated with Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae) throughout development in naturally attacked trees. Isolations of fungi were made from phloem adjacent to brood and from brood exoskeletons and guts. Overall, the incidence of fungi with individual brood increased as brood development progressed. Grosmannia clavigera (Robinson-Jeffrey and Davidson) Zipfel, de Beer and Wingf. and Ophiostoma montium (Rumbold) von Arx exhibited generally opposing trends in prevalence. G. clavigera was most likely to be found in phloem adjacent to prewintering third- and postwintering fourth instar larvae. O. montium was most likely to be found in phloem adjacent to eggs, first-instar larvae, pupae, and teneral adults. In contrast to isolations made from phloem, fungi isolated from brood guts and exoskeletons were not observed to shift in prevalence. First- and third-instar larvae were often observed migrating to older portions of their galleries, indicating that they do not spend all of their time feeding at, and extending, the apex of the gallery. Our results suggest that not only are D. ponderosae brood in contact with and feeding on fungi throughout development, but also, that during development, contact of brood with a particular fungus is likely to change. Such temporal shifts in fungal symbionts may be environmentally driven and have important implications in how these fungi interact with their hosts within and across generations. PMID- 17349119 TI - Effect of low temperatures on mortality and oviposition in conjunction with climate mapping to predict spread of the root weevil Diaprepes abbreviatus and introduced natural enemies. AB - The tropical root weevil, Diaprepes abbreviatus (L.), has been a pest of citrus and ornamental plants since its introduction into Lake County, FL, in 1964. Since then, it has colonized the Florida peninsula to the south of its point of introduction but has not expanded its range to the north. A lower threshold for oviposition by D. abbreviatus was estimated as 14.9 degrees C. Eggs were highly susceptible to cold, with 95% mortality (LTime95) occurring in 4.2 d at 12 degrees C. Relative susceptibility of life stages to cold was eggs > pupae > larvae > adults. Archived weather data from Florida were examined to guide a mapping exercise using the lower developmental threshold for larvae (12 degrees C) and the lower threshold for oviposition (15 degrees C) as critical temperatures for mapping the distribution of D. abbreviatus and the potential for establishment of egg parasitoids. Probability maps using the last 10 yr of weather data examined the frequency of at least 10, 15, 20, 25, or 30 d per winter when soil temperature was 5 mo, which is the duration of the cotton-free season in the subtropical Lower Rio Grande Valley of Texas and other cotton-growing areas in the Western Hemisphere. Cotton, Gossypium hirsutum L., and the boll weevil occur in the same areas with one or all three plant species (or other citrus and Opuntia species that might also nourish boll weevils) from south Texas to Argentina. Although adult boll weevils did not produce eggs when fed exclusively on the endocarps of prickly pear, orange, or grapefruit, these plants make it possible for boll weevils to survive from one cotton growing season to the next, which could pose challenges to eradication efforts. PMID- 17349123 TI - Intercolony aggression within and among local populations of the invasive ant, Myrmica rubra (Hymenoptera: Formicidae), in coastal Maine. AB - Myrmica rubra L. was introduced into New England in the early 20th century, and at present, has a patchy distribution in parts of northeastern North America, including records from 31 communities in Maine. M. rubra is highly polygynous, and colonies reproduce vegetatively, forming dense local populations where conditions are favorable. Using mobile nests and baited arenas in a series of field aggression bioassays, we tested patterns of internest tolerance within and among local populations on Mt. Desert Island, ME. We found that foragers originating from fragments of the same colony or from neighboring nests retained a high level of intraspecific tolerance over several months, whereas significant intercolony aggression among workers was present between colonies within the same local patch separated by approximately 10 m. Within populations, aggression score values were found to increase linearly with internest distance within a site. Aggression was highest between colonies from spatially different populations on the island and was higher still when nests were assayed against colonies at an off-island site 70 km away in Castine, ME. These data strongly suggest a multicolonial organization within and among local populations of M. rubra in parts of its introduced range. These findings contradict the loss of intraspecific aggression and unicolonial social structure over large geographic areas that have previously been observed in other invasive ant species, particularly Linepithema humile Mayr. PMID- 17349124 TI - Ips pini (Curculionidae: Scolytinae) is a vector of the fungal pathogen, Sphaeropsis sapinea (Coelomycetes), to Austrian pines, Pinus nigra (Pinaceae). AB - Sphaeropsis sapinea (Fr.:Fr.) Dyko and Sutton, is among the most common and widely distributed pathogens of conifers worldwide. S. sapinea is disseminated over short distances by rain splash and moist wind, but significant knowledge gaps regarding long-range dispersal remain. Our objective was to determine whether or not the pine engraver beetle, Ips pini Say, is a vector of the pathogen onto Austrian pines (Pinus nigra Arnold). In 2004 and 2005, individuals of I. pini were collected with pheromone traps at two locations in central Ohio (197 and 1,017 individuals for 2004 and 2005, respectively) and screened for the presence of S. sapinea. In the field, fresh logs of Austrian pine were baited with pheromone lures, mechanically wounded, or left undisturbed. After 2 mo, logs were evaluated for insect feeding and the presence of S. sapinea along beetle galleries. Fresh logs were also inoculated in the greenhouse with adult I. pini that were either artificially infested or uninfested with S. sapinea spores to determine vectoring potential. Phoresy rates for individual collections ranged from 0 to 4.1%; average rates were 1.5 and 2.0% for 2004 and 2005, respectively. Isolation frequencies of S. sapinea from baited (15 +/- 5%) and unbaited logs (3 +/- 1%) differed significantly (P=0.009). I. pini was also capable of transmitting the pathogen under controlled conditions. Based on phoresy rates, association, and artificial inoculation studies, we conclude that I. pini is able to transmit S. sapinea to Austrian pine stems. PMID- 17349125 TI - Nontarget effects of transgenic insecticidal crops: implications of source-sink population dynamics. AB - Widespread planting of transgenic insecticidal (TI) crops for pest control has raised concerns about potential harm to nontarget arthropods. Because the first generation of TI crops produce single Bacillus thuringiensis (Bt) toxins causing little or no harm to most nontarget arthropods, they are not likely to cause such negative effects. However, varieties of transgenic crops with multiple Bt toxins or novel toxins might be more harmful to nontarget arthropods. Field studies assessing nontarget effects typically compare the relative abundance of nontarget arthropods in TI crop fields to non-TI crop fields. However, for nontarget arthropods that are killed by TI crops, such analyses may miss important effects. Results from simulations of a spatially explicit population dynamics model show that large-scale planting of TI crops could cause three types of negative effects on nontarget arthropods that suffer mortality caused by TI crops: (1) lower abundance in TI fields than non-TI fields with little or no effect on abundance in non-TI fields, (2) lower abundance in TI fields than non-TI fields and decreased abundance in non-TI fields, and (3) loss of the arthropod from TI and non-TI fields. Simulation results show that factors increasing the potential for negative effects of TI crops on nontarget arthropods in non-TI fields are low reproduction, high emigration, high adoption of TI crops, high mortality in TI fields, insecticide sprays, and rotation of TI and non-TI fields. The results suggest that risk assessment should consider the regional distribution of transgenic crops and the life history traits of nontarget arthropods to identify the most vulnerable regions and nontarget species. PMID- 17349126 TI - Postfire succession of saproxylic arthropods, with emphasis on coleoptera, in the north boreal forest of Quebec. AB - Saproxylic succession in fire-killed black spruce [Picea mariana (Mill.) B.S.P.] coarse woody debris (CWD) in northern Quebec is estimated in this study using a 29-yr postfire chronosequence. Sampling was performed using both trunk-window traps and rearing from snag and log sections. A total of 37,312 arthropods (>220 taxa) were collected from both sampling methods. Two distinct colonization waves were identified. The onset of initial colonization occurs the year of the fire, whereas the second colonization phase begins only once debris falls to the ground. The initial colonization step is influenced by fire-associated species including subcortical predators, xylophages, and ascomycetes feeders. Abundance of most early colonizer species decline with time since fire with the disappearance of subcortical habitat. No noticeable species turnover occurred in snags thereafter. Lack of succession in snags is related to very low decomposition rates for postfire CWD because this substrate is unsuitable for species associated with highly decayed wood. Snag falling triggers fungal growth and concomitant saproxylic succession toward micro- and saprophagous species and increases accessibility for soil-dwelling organisms. Because the position of woody debris greatly influences overall physical properties of dead wood, the fall of burned CWD plays a major role in saproxylic community shift after fire. PMID- 17349127 TI - Olfactory and visual stimuli affecting host plant detection in Homalodisca coagulata (Hemiptera: Cicadellidae). AB - The relative effects of visual and olfactory stimuli on host plant detection in immature and adult Homalodisca coagulata Say (Homoptera: Cicadellidae) were studied using a novel olfactometer and factorial experimental designs. Colored, gray, and white cards were used as visual targets. Each card was attached to a glass thistle tube from which host-plant odor (from Vigna unguiculata L.) or blank, humidified air was dispensed. Visual + odor stimuli combinations were presented in no-choice tests. Nymphs were released onto a perch stick downwind from the target. Nymph response to color + odor treatments was measured by the duration of orientation behavior, residence time on the perch, and percentage of individuals that jumped to the target. The assay was modified so that adults crawled from the perch onto the target. Adult response was measured by the duration of individual behaviors (e.g., foraging) and by their position and residence time on the target. Both main effects and interactive effects of the stimuli were observed. Nymphs showed a decrease in orientation and residence times in the colored target + host odor treatments and increased jumping response in the gray + host odor treatment. When adults were exposed to host odor, the duration of foraging behavior increased, whereas crawling and phototactic behaviors decreased. Although nymphs and adults responded to visual stimuli + blank air treatments, host odor enhanced their responses. The primary effect of host odor on host detection behavior may be to enhance H. coagulata responsiveness to visual cues. PMID- 17349128 TI - Modeling Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) damages on cotton. AB - We studied and modeled damage caused by Helicoverpa armigera larvae on cotton with the aim of developing a coupled crop pest model. Two damage components were studied: the voracity (quantity of fresh matter and number of organs consumed) and feeding preferences (type of organ infested). The laboratory no-choice study of voracity on excised squares and bolls revealed that an H. armigera larva consumes 2,856 mg of fresh matter throughout its larval life, with the sixth instar consuming 86% of this quantity. This consumption rate corresponded to 23.6 squares, or 7.8 bolls. We developed equations to predict the quantity of fresh matter uptake from an individual plant organ, according to the organ mass and the larval instar. The field study of feeding preference confirmed previous findings that larvae prefer squares to bolls, with this preference decreasing as the larval age increases. However, no significant relationship was noted between the age of larvae and the size of infested organs within each organ class (square or boll). We developed a logistic model to predict the probability of a larva infesting a boll rather than a square. According to this model, the relative organ availability in the field and the larval instar were found to be significant factors. PMID- 17349129 TI - Multiple mating of male and female codling moth (Lepidoptera: Tortricidae) in apple orchards treated with sex pheromone. AB - Studies were conducted with codling moth, Cydia pomonella L., to evaluate the mating status of male and female moths in apple, Malus domestica (Borkhausen), orchards treated with and without sex pheromone dispensers. Laboratory studies first examined the effect of multiple mating of male and female moths on female fecundity and egg fertility. Females that had mated three times had a significantly higher fecundity than singly mated moths. Sequential mating by male moths had no effect on the fecundity of female moths or egg fertility. However, male moth age did impact female fecundity, with significantly fewer eggs laid after mating with virgin 1- versus 3-d-old males. The mean size of the first spermatophore transferred by males was significantly larger than all subsequent spermatophores. Classifying spermatophores based on size was used in field sampling to categorize the mating status of the female's partner. The proportion of mated females with small spermatophores (partner had previously mated) was significantly higher in treated versus untreated orchards. The proportion of female moths caught in traps baited with pear ester that were virgin was low (or= 0.192 and Nm 0.05). (3) Both VEGF-mRNA and Flk-1-mRNA significantly increased on the 14(th) day and the 18th day (P < 0.05). On the 25(th) day, the amounts of VEGF mRNA and Flk-1-mRNA were similar between the control and oxygen group (P > 0.05). CONCLUSION: Fluctuation in oxygen is associated with the development of retinal neovascularization in the retinopathy. Increased expressions of VEGF and Flk-1 in the oxgen fluctuations-induced neovascularized retina suggested that VEGF and Flk 1 might play a critical role in the pathogenesis of ROP. The results also indicated the positive feedback in the pathogenesis of ROP that the synergistic interaction of VEGF and Flk-1 in the retinal vascular proliferation. These findings provide insight into the effect of repeated oxygen fluctuation on the development of severe ROP in preterm infants. PMID- 17349141 TI - [Role of different oxygen concentration and different period of oxygen exposure in pathogenesis of retinopathy in neonatal mice]. AB - OBJECTIVE: To evaluate the role of different oxygen concentration (FiO2) and different period of oxygen exposure on oxygen-induced retinopathy (OIR) in neonatal mice and to provide evidences for proper clinical oxygen therapy. METHODS: Two hundred and four 7-day-old (P7) C57BL/6J mice were exposed to different FiO2 30%, 50% and 75% for 5, 7 and 9 days. The mice were divided into eight groups: groups 1 - 3 (n = 24 in each) were exposed to 30% oxygen for 5, 7 and 9 days, respectively; groups 4 - 6 (n = 24 in each) were exposed to 50% oxygen for 5, 7 and 9 days, respectively; group 7 (n = 30) was exposed to 75% hyperoxia for 5 days; group 8 (n = 30) was exposed to room air. Proliferative neovascular responses were estimated by observing vascular patterns in adenosine diphosphate-ase (ADPase) stained retina flat-mounts and quantitated by counting the number of new vascular cell nuclei extending into the internal limiting membrane in cross-sections. RESULTS: (1) Vascular patterns in retina flat-mounts: a) When FiO2 was 30%, the entire vascular pattern was completely normal after 5 and 7 days exposure; although the deep vascular system seemed slightly constricted after 9 days exposure, it recovered 2 days later and matured at P21. b) When FiO2 was 50%, after 5 days exposure (group 4), the larger vessels constricted and central perfusion decreased moderately; after exposing to room air for 2 days, neovascularization was seen; however, the entire vascular pattern was almost normal at P17. After 7 days of exposure to 50% O2 (group 5), the vascular pattern recovered a bit, seemed to be better than that of group 4; after 9 days of exposure to 50% O2 (group 6), only slight constriction could be seen and it disappeared 2 days later and all vessels matured later. c) When FiO2 was 75%, after 5 days exposure to hyperoxia, the larger vessels became tortuous and constricted, central perfusion became decreased obviously; after exposing to room air for 2 days, neovascularization was seen; and this response was maximal at P17 - P21. However, the mortality of nurser mice and pups increased dramatically when the duration of hyperoxia was prolonged. (2) Quantitative results in cross sections: neovascular nuclei extending into the vitreous reached (41.9 +/- 2.8) per section in 75% oxygen group, while less than 1 in every other groups, which was statistically different (P < 0.0001). CONCLUSIONS: FiO2 and the duration of hyperoxia could affect retinal vascular development. Low and moderate FiO2 could induce reversible vessel changes, while high FiO2 induced irreversible changes which should be avoided in clinic. PMID- 17349142 TI - [Dilated cardiomyopathy in a neonate]. PMID- 17349143 TI - [Amplitude-integrated electroencephalographic monitoring in early diagnosis and neurological outcome prediction of term infants with hypoxic-ischemic encephalopathy]. AB - OBJECTIVE: To study the changes of the amplitude-integrated electroencephalography (aEEG) tracings within 6 hours after birth in term infants with hypoxic-ischemic encephalopathy (HIE) and explore the value of aEEG in early diagnosis and prediction of neurological outcome in term infants. METHODS: From May 2003 to February 2005, 33 term infants with HIE at the Division of Neonatology, Pediatric Hospital of Fudan University were studied by aEEG within 6 hours after birth. The results of aEEG were categorized into three groups (normal, mildly abnormal and severely abnormal aEEG), while HIE was clinically classified into three grades (mild, moderate and severe) and the neurological outcomes at 18 months were assessed (normal, disabled and dead). The correlation between the results of aEEG, severity of HIE and neurological outcome at 18 months were analyzed, respectively. The values of aEEG on early diagnosis and neurological outcome prediction of HIE were analyzed. RESULTS: Among the 33 term infants with HIE, 20 infants had normal aEEG (normal amplitude aEEG), 5 had mildly abnormal aEEG (4 with mildly abnormal amplitude aEEG, 1 with normal amplitude and seizure) and 8 had severely abnormal aEEG (2 with mildly abnormal aEEG and seizures, 4 with severely abnormal amplitude and 2 with severely abnormal amplitude and seizures), respectively. Seventeen infants (51.5%) had mild HIE, 19 moderate (27.3%) and 7 (21.2%) severe HIE, respectively. Twenty-five cases were followed up, which showed that 19 had normal neurological outcome, 1 had disability and 5 died. By CMH square analysis and Spearman rank correlation analysis, the results of aEEG classification were correlated with the severity of HIE and the neurological outcome of term infants. Abnormal aEEG could predict the severity of HIE in term infants with a sensitivity of 100%, specificity of 81.3%, positive predictive value of 85.0% and negative predictive value of 100%, respectively. Abnormal aEEG could predict the neurological outcome of term infants with HIE, which showed a sensitivity of 100%, specificity of 90.9%, positive predictive value of 93.3% and negative predictive value of 100%, respectively. Severely abnormal aEEG could predict the severe HIE in term infants with sensitivity of 96.2%, specificity of 100%, positive predictive value of 100% and negative predictive value of 87.5%, respectively. Severely abnormal aEEG could predict the neurological outcome of term infants with HIE, which showed sensitivity of 94.7%, specificity of 100%, positive predictive value of 100% and negative predictive value of 85.7%, respectively. CONCLUSIONS: Monitoring with aEEG in term infants with HIE within 6 hours after birth could predict the severity of HIE and its neurological outcome at 18 months. PMID- 17349144 TI - [Changes of globus pallidus in the newborn infants with severe hyperbilirubinemia]. AB - OBJECTIVE: The involvement of globus pallidus has been found in neonates with acute bilirubin encephalopathy (ABE), but so far the relationship between the severity of hyperbilirubinemia and changes of globus pallidus has not been studied further. The present study was conducted to understand possible relationship between the MRI signal changes of globus pallidus and severe hyperbilirubinemia in the neonates to provide evidences for diagnosis of bilirubin encephalopathy and prediction of outcome. METHODS: Thirty-six neonates with severe hyperbilirubinemia (total serum bilirubin, i.e., TSB > 342 micromol/L) received MRI examination in a magnetic field with the strength of 1.5 - 3.0 Tesla at ages of 10 +/- 6 (2 - 34) days of life, of whom 15 were assessed as acute bilirubin encephalopathy (ABE). Routine T1WI with three kinds of sequences (SE, IR and FFE), T2WI and DWI with two kinds of sequences (EPI-SE and DW SSh SENSE) were applied. Two neuroradiologists who knew nothing about the clinical history analyzed MRI findings. TSB, unconjugated bilirubin (UCB), conjugated bilirubin (CB) and albumin (ALB) in all these neonates were measured with the same methods and analyzer. RESULTS: Symmetric hyperintense globus pallidus was shown on T1WI in 20 neonates, of whom three had symmetric hyperintense globus pallidus on T2WI (TSB = 745.3 micromol/L, 735.7 micromol/L, 707.6 micromol/L, respectively) at the same time. Remarkably higher TSB, molar ratio of TSB and ALB (B/A) and UCB were found in 20 neonates with hyperintense globus pallidus as compared to 16 cases without changes of globus pallidus (P = 0.000). No abnormal signal changes were found on DWI for all neonates; 9 neonates with TSB ranged from 342.0 micromol/L to 427.5 micromol/L did not show any abnormalities of globus pallidus, 3 of 7 neonates with TSB ranged from 427.5 micromol/L to 513.0 micromol/L, but 17 of 20 neonates with TSB more than 513.0 micromol/L showed distinct hyperintense globus pallidus. Hyperintense globus pallidus on T1WI was related to the severity of hyperbilirubinemia (Fisher's Exact Test, P = 0.000). Hyperintense globus pallidus on T1WI was found in all the 15 neonates with ABE (Fisher's Exact Test, P = 0.000), at the same time, hyperintense globus pallidus on T2WI was found in 3 cases with severe ABE. Six infants received the second MRI at ages from 2 months to 12 months, two of three infants with ABE in neonatal period showed the signal changes of globes pallidus from T1WI hyperintensity to T2WI hyperintensity and they developed cerebral palsy. The other one with normal signal showed hearing dysfunction. Another three infants without history of ABE did not show abnormal signals of globus pallidus and developed normally. CONCLUSIONS: The symmetric involvement of globus pallidus with hyperintense signals on MRI T1WI indicates the severity of hyperbilirubinemia, which relates to time of exposure to hyperbilirubinemia and is a characteristic finding of ABE. The signal switch of hyperintense globus pallidus from T1WI to T2WI predicts poor outcome. PMID- 17349145 TI - [Protective effect of N-acetylcysteine against lipopolysaccharide injury in hepatocytes of neonatal mice]. AB - OBJECTIVE: N-Acetylcysteine (NAC) is a sulfhydryl donor molecule with antioxidant and antiinflammatory effects. A major role has been described for inducible nitric oxide (NO) synthase in several inflammatory liver diseases. NAC attenuates NO generation following lipopolysaccharide injection in rats. The purpose of this study was to investigate the effect of NAC against lipopolysaccharide injury in hepatocytes of neonatal mice and the molecular mechanisms by which NAC influences inflammatory responses of the hepatocytes. METHODS: The liver of neonatal mouse was digested by collagenase to dissociate the hepatocytes. The hepatocytes were cultured and isolated. After 7 days of culture the normal hepatocytes were divided into two groups: LPS group and NAC group. In LPS group, 10 microg/ml LPS was added into the culture medium. In NAC group, 5 mmol/L NAC was added into the culture medium firstly, 10 microg/ml LPS was added after 1 h of culture. There were 12 mice in each group. The cell supernatants and the hepatocytes were collected at 0, 6 and 12 hours after adding LPS. The cell supernatants were taken to measure the alanine aminotransferase (ALT) level and nitric oxide (NO) production by the biochemical methods. The cells were taken to analyze the gene expression of induced nitric oxide synthase (iNOS) by the RT-PCR. RESULTS: In LPS group, the levels of ALT, NO and iNOS mRNA increased significantly at the time points 6 h and 12 h compared with the time point 0, (P < 0.01). Compared with the LPS group, the levels of ALT, NO and iNOS mRNA of NAC group were lower at the time points 6 h and 12 h (P < 0.01). CONCLUSIONS: NAC may play a protective role in the hepatocytes injury caused by LPS in the neonatal mice. The protective mechanism works partially through the inhibition of iNOS activation by LPS. PMID- 17349146 TI - [Diagnostic suggestions for periventricular-intraventricular hemorrhage and periventricular leukomalacia in premature infants]. PMID- 17349147 TI - [Summary of the symposium on critical care in neonates and children]. PMID- 17349148 TI - [Report of a case with Treacher Collins syndrome]. PMID- 17349149 TI - [Neonatal lupus erythematosus]. PMID- 17349150 TI - [Isolation of human metapneumovirus from children with acute respiratory tract infection in Chongqing, China]. AB - OBJECTIVE: To isolate and characterize the newly discovered human metapneumovirus (hMPV) in Chongqing, China and elucidate the clinical manifestations of hMPV infection. METHODS: Eighty-six patients hospitalized for acute respiratory tract infection in Children's Hospital, Chongqing University of Medical Sciences from December 2004 to July 2005 were enrolled in the present study. Nasopharyngeal aspirates were collected for screening for common respiratory viruses by direct immunofluorescence assay, including respiratory syncytial virus, influenza virus types A and B, parainfluenza virus types 1, 2, 3 and adenovirus, and for inoculating onto Vero-E6 and LLC-MK2 cells for hMPV isolation. Cultures were maintained in the presence of trypsin and observed for development of cytopathic effect (CPE) for 3 weeks. Presence of hMPV was first indicated by positive CPE and subsequently confirmed by reverse transcription polymerase chain reaction targeting N and F genes. Sequence of amplified F fragments were analyzed and submitted to NCBI GenBank. The clinical findings of hMPV infection were collected and analyzed. RESULTS: Of the collected 86 NPAs, six showed CPE characterized by clustering of infected cells, increased granules and eventuall detachment from cell monolayer and obvious syncytium formation. Successful isolation of hMPVs was confirmed with RT-PCR targeting hMPV F and N genes. Of the six hMPV-positive specimens, two were collected in winter (December, January), two in spring (May) and the other two in autumn (June, July). All the six patients were younger than 2 years of age with disease spectrum of bronchiolitis (2/6), bronchopneumonia (2/6), infantile asthma (1/6) and upper respiratory tract infection (1/6). Clinical findings included fever, cough, wheezing, polypnea, cyanosis and rales. Parainfluenza 3 and adenovirus seemed to beviral pathogens of co-infection. CONCLUSION: Six hMPVs were successfully isolated in the mainland of China for the first time. HMPV appears to be one important viral pathogen for acute lower respiratory tract infections in young children with a detection rate of 7% (6/86) by viral isolation. The virus causes respiratory diseases similar to those caused by respiratory syncytial virus. These findings highlight the need for future investigations to define disease burden of hMPV infection and molecular epidemiology among children in China. PMID- 17349151 TI - [Association of the vitamin D receptor gene start codon polymorphism with delayed rickets]. AB - OBJECTIVE: Delayed rickets is a special type of vitamin D deficiency, the occurrences of delayed rickets mainly relate to vitamin D deficiency, but whether there is hereditary susceptibility of children to development of delayed rickets is unknown. Recently some studies suggest that there is a significant association between vitamin D receptor gene (VDR) polymorphism and the metabolic diseases of bone. The present study aimed to explore the hereditary susceptibility of children to development of delayed rickets through studying the association of the vitamin D receptor gene start codon (VDRSC) polymorphism with delayed rickets. METHODS: The diagnosis was based on clinical, biochemical and radiological data. The subjects were composed of three groups, the patient group had 30 children, the vitamin D deficiency group 35 children, and the control group 60 normal children. The VDRSC genotypes of the three groups were determined by using polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) technique. RESULTS: There was significant difference in the frequencies distribution of VDRSC genotypes (chi(2) = 13.184, P = 0.010) and VDRSC alleles (chi(2) = 8.975, P = 0.011) among the three groups; the frequency of the FF genotype (56.7%) in the patient group was significantly higher than that in the control group (21.7%, P = 0.006) and that in the vitamin D deficiency group (22.9%, P = 0.002). The frequency of the F alleles in the patient group (70.0%) was significantly higher than that in the control group (48.3%, P = 0.006) and that in the vitamin D deficiency group (47.1%, P = 0.009). Multiple logistic regression analysis showed that FF genotype had a higher risk of delayed rickets (OR = 3.120), indicating that FF genotype may be significantly associated with delayed rickets. CONCLUSION: There is the possibility that the VDRSC polymorphism might be important in determining the hereditary susceptibility of children to development of delayed rickets. PMID- 17349153 TI - [Early intervention for children with language developmental delay]. AB - OBJECTIVE: To explore the mode of intervention for children with language developmental delay under the current condition of China. METHOD: The study population consisted of a cross-sectional convenience sample of 206 children, ages 13 - 24 months, from six communities of Qingpu in Shanghai. Parents were asked to complete detailed questionnaires about their child's spontaneous use of vocabularies. Fourteen children with vocabularies less than 5 percentile of every age group were identified as having language developmental delay. During the 12 month intervention, developmental pediatricians did the developmental assessment for every child and set goals of intervention for everybody according to their language abilities and family situation. Then kindergarten teachers who got the training in language therapy carried out the intervention. Gesell development scale was used for developmental assessment before and after the intervention. RESULTS: The developmental quotient (DQ) in areas of language and personal-social behavior was elevated significantly after 12 months of intervention (P < 0.01). The developmental quotient (DQ) in the area of adaptive behavior was also elevated (P < 0.05). There was an obvious catching up effect in both areas of language and personal-social behavior. Increased developmental age in both areas was (18.0 +/- 5.3) months and (16.2 +/- 5.9) months, respectively. The language ability of 71.4% samples was in the normal range at the end. CONCLUSIONS: The mode of medical and educational cooperation to give early intervention for children with language developmental delay is feasible. It can significantly improve the abilities in language and communication of children 1 - 2 years of age. PMID- 17349154 TI - [A study on the (CA)n in FVIII gene in Han ethnic group in Guangxi Zhuang Autonomous Region by amplification polymorphisms combined with silver staining]. AB - OBJECTIVE: Hemophilia A is an inherited bleeding disorder caused by defects in factor VIII (FVIII) gene. In the present study, the frequencies of the microsatellite alleles at introns 13 and 22 in the factor VIII gene were analyzed in the group of Han nationality in Guangxi Zhuang Autonomous Region to explore their diagnostic value for hemophilia A. These two sites were also used to detect the carriers in 13 hemophilia A families. METHODS: Ninty-one individuals of Han ethnic group in Guangxi Zhuang Autonomous Region (135 X chromosomes) and 13 HA families were subjected to molecular studies. First, these two fragments were PCR amplified simultaneously. Then, silver staining was used later to show their polymorphisms. The investigators selected one sample at random to obtain its lengths of the PCR products at these two sites by ABI310 PCR amplifier. After counting its repeated numbers of (CA) according to the documents concerned, the repeated numbers of the other samples could be counted easily. RESULTS: In the 91 individuals, 6 and 4 alleles were detected at these two sites, respectively. At intron 13 the allele frequencies ranged from 0.0002 to 0.5408 and polymorphism information content (PIC) was 0.5899. At intron 22 the allele frequencies ranged from 0.0444 to 0.4963 and its PIC was 0.5359. The actual heterozygosity for intron 13 and intron 22 were 0.6364 (28/44) and 0.5227 (23/44), respectively. In 13 hemophilia A families with positive history, 9 of them were diagnosed by this method and the diagnosis rate was 69%. CONCLUSION: With high PICs, (CA)n at intron 13 and intron 22 were two valuable sites in the diagnosis of hemophilia A in the population of Han ethnic group in Guangxi Zhuang Autonomous Region. Compared with some other HA restrictive fragment length polymorphisms (RFLP), intron 22 (GT)n (AG)n was more informative. PMID- 17349155 TI - [Etiologic and clinical characteristics of syncope in children]. AB - OBJECTIVE: Syncope is a common problem in children and adolescents. Such an event may have multiple possible causes, ranging from benign conditions to life threatening diseases. Syncope is a major challenge for the practicing physicians. It is very important to know the etiologic and clinical characteristics of syncope in children. This study aimed to improve diagnostic efficacy of syncope in children by analyzing the etiology and clinical characteristics of syncope. METHODS: The investigators retrospectively analyzed the causes of syncope and diagnostic workup of 154 consecutive children seen in Department of Pediatrics, Peking University First Hospital because of a syncopal event. RESULTS: Autonomic mediated reflex syncope (AMS) was the most common cause of syncope (65.6%), whereas cardiac disorders were found in 10 cases (6.5%) comprising the second cause of syncope in children. Other causes included psychologic problems and neurological and metabolic disorders. Although many causes were studied, 25 cases (16.2%) were found to have uncertain etiologies yet. The children with AMS were commonly seen in pubertal girls, and they had clear inducement of syncope and prodromes. The children with cardiac syncope often had history of cardiac diseases, and they were often younger than those with AMS. Lack of prodromes of syncope, exercise-related syncope, syncope spells seen in any body position, frequent syncope spells and sudden death in family were clues of cardiac syncope. Neurological disorders should be considered if there are any of the followings: syncope with seizure activity, syncope spells seen in any position, and a postictal phase of disorientation or neurologic abnormal signs. A metabolic cause was entertained when the child had a history of metabolic diseases, prolonged anger, or violent vomiting and diarrhea. Children with psychiatric disorders were adolescent girls with prolonged syncope spells, and had more frequent syncopal episodes. Most children with syncope were evaluated by many of diagnostic tests, but most of those tests were not goal-directed approach. Since persons with cardiac syncope were at increased risk for death from any cause, electrocardiography was recommended in almost all children with syncope. Neurologic testing including electroencephalography, computed tomography, etc. were rarely helpful unless neurologic signs and symptoms are present. Holter electrocardiography and echocardiography were most useful in children with suspected cardiac syncope. There was little benefit of screening cardiac enzyme in children with syncope. Routine blood tests (blood electrolytes and blood glucose, etc) rarely yield diagnostically useful information unless the children had the history of metabolic diseases. Head-up tilt testing was most useful in children with recurrent syncope in whom heart disease was not suspected. The children with frequent syncope, long lasting syncopal episode and clear psychiatric inducement of syncope should be evaluated by psychiatric testing. CONCLUSION: Syncope in children may result from a wide variety of causes, and clinicians often use a wide range of investigation to try to achieve a diagnosis. But most of investigations have low diagnostic yield. Thorough history taking, physical examination and electrocardiography are the core of the syncope workup. PMID- 17349157 TI - [Answers to the questions concerning the skin test for the use of penicillins or cephalosporins in neonates]. PMID- 17349156 TI - [In vitro expansion and function of cord blood megakaryocyte]. AB - OBJECTIVE: Cord blood (CB) provides a rich source of stem cells for transplantation. CB transplantation has been used widely after myeloablative therapy. One major disadvantage of CB transplantation is delayed platelet engraftment. The aim of this study was to hasten platelet engraftment by investigating the ability of different hematopoietic growth factor combinations to generate large numbers of megakaryocyte (Mk) from CB and by evaluating the biologic characteristics and function of the expanded Mk. METHODS: CB samples were obtained at the end of normal full-term deliveries with informed consent. Mononuclear cells (MNCs) were isolated from CB using Ficoll density centrifugation. MNC population was positively selected for CD(34) expression by magnetic cell sorting (MACS). CD(34)(+) cells were cultured in serum-free and stroma-free medium containing the following two different cytokine combinations: thrombopoietin (TPO) + stem cell factor (SCF) + interleukin (IL) -3 + IL-6 and TPO + SCF. Cultures were characterized after 3, 7, 10 and 14 days by flow cytometry, colony forming unit-megakaryocyte (CFU-Mk) and maturation evaluation (Mk ploidy). The expanded Mk function was examined by the platelet activation in vitro and severe combined immunodiffiency (SCID) mice transplantation in vivo. RESULTS: Different results were observed with different culture conditions. With the first cytokine combination optimal expansion of CD(41)(+) cells was observed on day 10, but the optimal expansion of Mk progenitors (CD(34)(+)CD(41)(+)) was observed on day 7, with a median 121 and 44-fold increase at the starting cell dose. This result was also proven by CFU-Mk. The largest numbers of CFU-Mk were also observed on day 7. The degree of maturation of Mk cells also increased as suggested by DNA content of CD(41)(+) cells, which means that CD(34)(+) cells cultured for 3 - 7 days were richer in primitive Mks, while those cultured for 10 - 14 days had greater numbers of more differentiated Mks. For the second cytokine combination, CD(41)(+) and CD(34)(+)CD(41)(+) cells were fewer than the first one, but it produced 36 and 85-fold CD(34)(+)CD(41)(+) and CD(41)(+) respectively on day 7. Platelet activation test confirmed that the expanded Mks had normal function. Therefore, the expanded Mks could be transplanted into the SCID mice bone marrow and produce human platelet in the peripheral blood of the mice. CONCLUSION: Ex vivo expanded Mk might facilitate CB transplantation and help shorten the period of post-transplant thrombocytopenia. PMID- 17349158 TI - [Effect of correlative factors for indomethacin treatment of hemodynamically significant patent ductus arteriosus in extremely low birth weight infants]. PMID- 17349159 TI - [Treatment of 14 children with hematological diseases with cord blood transplantation]. PMID- 17349160 TI - [Expression of PTEN mRNA, hTERT and DNA-PKcs in bone marrow cells of children with acute leukemia]. PMID- 17349161 TI - [Detection of cardiac actin and desman gene mutations in children with dilated cardiomyopathy]. PMID- 17349162 TI - [High dose methotrexate induced acute renal insufficiency in a patient with acute lymphoblastic leukemia]. PMID- 17349163 TI - [Recognition of the indication of orthotopic liver transplantation for hepatocellular carcinoma in China]. PMID- 17349164 TI - [The study of the different medicating ways and the formula for intravenous loading dosage of hepatitis B immunoglobulin in liver transplantation]. AB - OBJECTIVE: To evaluate the efficacy and safety of hepatitis B immunoglobulin (HBIG) by different medicating ways in patients with liver transplantation and to explore the methods for calculating the intravenous loading dosage of HBIG. METHODS: The patients enrolled were randomized into three groups (i.v group, i.m group and domino group). Under the combined utilization with Lamivudine, HBIG was given in different ways during anhepatic phase and the postoperative six days. The physical examination was done, the serum conversion rate of HBsAg was studied, the serum level of HBsAb titer, WBC, PLT, AST, GGT, TBIL, DBIL, CR, PT and PTA were tested daily within the postoperative seven days. The preoperative body weight, serum HBsAg and HBeAg titer were analyzed with the intravenous loading dosage of HBIG by multiple-factor linear regression (Stepwise). RESULTS: Both the average negative-conversion rate of serum HBsAg and the average increasing rate of serum HBsAb titer are significantly faster in i.v group and domino group than that in i.m group within the postoperative four days (P < 0.05). The regression equation to calculate the i.v loading dosage of HBIG (IU) by preoperative criteria was drawn as 1123 + 3.4 x serum HBsAg titer (IU/L) +73 x body weight (kg). There was no linear correlation found between the level of HBeAg and the loading dosage of HBIG. There were no significant difference in body temperature, pulse rate, respiratory rate, blood pressure, WBC, PLT, AST, GGT, TBIL, DBIL, CR, PT and PTA among the three groups within the postoperative seven days (P < 0.05). The rate of the second elevation of serum ALT was 10.3% (3/29), 3.4% (1/29) and 6.7% (2/30) in i.v group, i.m group and domino group, respectively (P < 0.05), and the rate of the local complications (sclerosis, edema, pain) at the injection site was 0, 89.6% (26/29) and 0, respectively (P < 0.05). CONCLUSIONS: Based on the combined utilization of lamivudine and HBIG, the qualified intervention efficacy, less complications could be obtained by medicating HBIG in a domino way (i.v first, followed by i.m), which is worthy to be promoted. PMID- 17349165 TI - [Surgical methods in living donor liver transplantation: with report of 50 cases]. AB - OBJECTIVE: To investigate and evaluate different surgical methods applied in living-donor liver transplantation (LDLT). METHODS: Fifty patients with end-stage liver disease received LDLT in our department between January 1995 and March 2006. The data were analyzed on a retrospective basis. The choice of different surgical methods, strategies applied to ensure the safety of donors and indications of LDLT in the series were reviewed. RESULTS: All donors recovered uneventfully. Among the 50 patients, 47 recipients presented with end-stage cirrhosis, 3 patients suffered from malignant tumor. To date, 6 recipients died after LDLT, among them, 3 recipients died of the operation and the other 3 recipients died of long-term complications. Resected donor livers included 9 cases of segments V, VI, VII and VIII (not including the middle hepatic veins) and 1 case of segments V, VI, VII and VIII (including the middle hepatic veins), 36 cases of segments II, III and IV (including the middle hepatic veins) and 4 cases of segments II, III, and part of IV (not including middle hepatic veins). CONCLUSIONS: LDLT helps tackle the problem of donor shortage in the world. The process is complicated, and it is very important to choose appropriate surgical methods for the improvement of surgical achievement and donor safety. PMID- 17349166 TI - [The practical value of endoscopic retrograde cholangiography in biliary complications after liver transplantation]. AB - OBJECTIVE: To investigate the practical value of endoscopic retrograde cholangiography (ERC) in biliary complications after liver transplantation. METHODS: The data of 71 biliary complications after liver transplantation were analyzed retrospectively. All patients were diagnosed and treated by ERC in our center from October 2003 to March 2006. The biliary complications included 52 cases of biliary stricture, 6 biliary leakage and 13 biliary stone. RESULTS: The diagnostic rate of ERC for biliary stricture, leakage and stone was 98.1% (51/52), 100% (6/6) and 100% (13/13), respectively. The cure rate of interventional therapy through therapeutic ERC for anastomotic, extrahepatic, hilar, intrahepatic and diffuse biliary stricture was 66.7% (4/6), 66.7% (10/15), 0 (0/7), 0 (0/2) and 0 (0/21), respectively. And that for biliary leakage, common bile duct and intrahepatic bile duct stone was 66.7% (4/6), 77.8% (7/9) and 0 (0/4), respectively. CONCLUSIONS: ERC is effective for diagnosis of biliary complications after liver transplantation. The effect of interventional therapy through ERC varies with the type of biliary complications. Only part of biliary complications (anastomotic stricture, extrahepatic biliary stricture, gently and moderate biliary leakage, common bile duct stone) can be cured by interventional therapy through ERC. PMID- 17349167 TI - [Investigation of intestinal bacterial translocation in 78 patients with cirrhosis after liver transplantation]. AB - OBJECTIVE: To investigate the prevalence and associated risk factors of bacterial translocation (BT) in patients with cirrhosis after liver transplantation and analyze the effect of BT on bacterial infection after the surgery. METHODS: Mesenteric lymph nodes (MLN), portal vein blood, and peripheral blood were collected during the liver transplantation for microbiological culture from 78 patients with cirrhosis. And meanwhile, all related clinical data were analyzed to investigate the risk factors of BT and its relationship with post-liver transplantation infections. RESULTS: BT was occurred in 8 of 78 cirrhotic patients (10.3%) and positive-rate of MLN culture was 5/8. Gram-negative aerobic bacillus was the main causative bacterium of BT (5/9), followed by Gram-positive aerobic enterococcus (22.2%, 2/9). Total bilirubin level in patients with BT was significantly higher than that in patients without BT. CONCLUSIONS: It suggests that hyperbilirubinemia is the only risk factor for BT, and BT is associated with an increased infectious rate after liver transplantation. PMID- 17349168 TI - [Study of cryopreservation of differentiated hepatocyte derived from human bone marrow stem cells]. AB - OBJECTIVE: To observe the viability and function of human bone marrow stem cell derived hepatocytes following cryopreservation in vitro. METHODS: Human bone marrow cells were induced to differentiate into hepatocytes in the presence of multiple factors. Mature hepatocytes were cryopreserved in 90% FBS and 10% DMSO (Group A), 10% FBS, 30% glycerol and 60% conditioned medium (Group B), and 10% FBS, 10% DMSO, and 80% UW solution (Group C). The cells were thawed after 4 weeks, and the cell viability and the albumin level were determined. RESULTS: The human bone marrow derived hepatocytes maintained functional morphology after thawing. The viabilities in Group A, B and C were (60.0 +/- 3.3)%, (91.0 +/- 2.6)%, and (89.0 +/- 1.4)%, respectively. After culturing for 24 h, the albumin levels in Group A, B and C were (0.210 +/- 0.005) g/L, (0.340 +/- 0.020) g/L and (0.330 +/- 0.030) g/L, respectively. CONCLUSIONS: Human bone marrow stem cell derived hepatocytes can maintain the viability and function after cryopreservation. These cells may contribute to an important source of hepatocytes for clinical hepatocyte transplantation and artificial liver support system. PMID- 17349169 TI - [CD4(+) CD25(+) Tr cells and transcription factor Foxp3 in the naturally tolerance of rat liver transplantation]. AB - OBJECTIVE: To investigate the role of intrahepatic CD4(+)CD25(+) T regulatory cells and Foxp3 gene in the natural tolerance in rat liver transplantation. METHODS: The orthotopic liver transplantation models of inbred rats (LEW and DA rats) were established with double-sleeve technique and the models were divided into two groups: tolerance group (TOL group, LEW-to-DA) and rejection group (REJ group, DA-to-LEW). The intrahepatic lymphocytes from each group were isolated by using density gradient centrifugation. CD4(+)CD25(+) T cells were isolated by magic cell sorting system (MACS) and identified by flow cytometry (FCM). CD4(+)CD25(+) Tr cells suppression on the proliferation of CD4(+)CD25(-) T effector cells were analyzed by cell proliferation assay in vitro. Western blot was used to detect Scurfin protein expression of CD4(+)CD25(+) Tr cells. RESULTS: CD4(+)CD25(+) Tr cells developed significantly greater in the TOL group than in the REJ group. In vitro, the spleen cells from LEW rats can irritate the proliferation of CD4(+)CD25(+) T cells more obviously than the syngeneic spleen cells. CD4(+)CD25(+) T cells could suppress the proliferation of CD4(+)CD25(-) T cells, but the inhibition was reversed by exogenous IL-2 (200 U/ml). CONCLUSIONS: The immune suppression function of CD4(+)CD25(+) Tr cell, mediated by Foxp3 gene, is one of the mechanisms in liver transplantation tolerance. PMID- 17349170 TI - [Adult posttransplant lymphoproliferative disease: report of 2 cases]. PMID- 17349171 TI - [Transplants Artery aspergillosis after Liver Transplantation: report of 1 case]. PMID- 17349172 TI - [Meeting Abstract of the 3rd Chinese academic conference on Organ Transplantation ]. PMID- 17349173 TI - [Diagnosis and treatment of postoperative complications after laparoscopic adjustable gastric banding procedure]. AB - OBJECTIVE: To investigate the diagnosis and treatment of the complications in patients after laparoscopic adjustable gastric banding (LAGB) procedure. METHODS: Retrospectively analyze the data of the 23 patients who received the LAGB procedure from June 2003 to November 2004. RESULTS: Of the 23 LAGB operations, 3 (13%) cases of vomiting and nausea, 1 (4.3%) case of access-port infection and 5 (21.4%) cases of food intolerance occurred. One band (4.3%) and one injection reservoir (4.3%) displaced and were removed by laparoscopy. No death and thrombo embolism occurred. CONCLUSIONS: The diagnosis and treatment of complications after LAGB in morbid obesity was special, if managed properly, the result would be satisfactory. PMID- 17349174 TI - [The first case of primary epithelial-myoepithelial carcinoma in the liver]. AB - OBJECTIVE: To report the first case of primary epithelial-myoepithelial carcinoma (EMC) in the liver. METHODS: The clinical manifestations, imaging characteristics, and histopathological changes of EMC in this case were described. The patient was a thirty-seven-year old female. A 10 cm lesion was detected in the right liver upon a routine examination. Following that, the CT scan, magnetic resonance imaging (MRI), repeated puncture biopsies, and serum alpha-fetoprotein (AFP) detection were done with no specificity and significance found. RESULTS: Right hemi-hepatectomy was performed. The special double catheterization cannula was found in the histopathological examination, and the final diagnosis of EMC was proven by immuno-histochemical staining. CONCLUSIONS: Primary EMC is difficult to be finally diagnosed prior to the surgery. The diagnosis can be confirmed using pathological examination and immuno histochemical staining of the specimen. PMID- 17349175 TI - [Study on monocyte HLA-DR expression in critically ill patients after surgery]. AB - OBJECTIVE: To explore the HLA-DR expression on CD14(+) monocyte in peripheral blood of critically ill patients after surgery and observe its relationship with prognosis of patients. METHODS: HLA-DR expression on CD14(+) monocytes in peripheral blood was measured in critically ill patients after surgery (30 cases) by using flow cytometry on the day 1, 4 and 7 after entered the ICU, and were compared with those in the healthy volunteers (28 cases). APACHE II score, sepsis related organ failure assessment (SOFA) score, age, sex and 28 d prognosis were recorded. RESULTS: The HLA-DR expression on CD14(+) monocyte in peripheral blood in critically ill patients after surgery were lower than that of healthy volunteers (P < 0.01). The CD14(+) monocyte HLA-DR expression on day 1 after entered ICU was not correlated with APACHE II score, SOFA and 28 d prognosis. However, compared with those with decreased HLA-DR expression, those with increased monocyte HLA-DR expression on day 7 had a better 28 d survival rate (P < 0.01). CONCLUSIONS: In critically ill patients after surgery, the decreased HLA DR expression on CD14(+) monocyte in peripheral blood on day 1 after entered ICU could not be regarded as a prognostic parameter, but it is significative to monitor the increased expression of HLA-DR on CD14(+) monocyte for evaluating the 28 d prognosis. PMID- 17349176 TI - [Differentiated thyroid carcinoma in children and adolescents: clinical characteristics and treatment]. AB - OBJECTIVE: To explore the clinicopathologic characteristics, treatment and prognosis of differentiated thyroid carcinoma (DTC) in adolescents. METHODS: The data of 46 patients with DTC under the age of 18 years were retrospectively reviewed. RESULTS: Twenty patients were misdiagnosed in this group (43.5%). All patients received operation, including 39 unilateral neck dissection and 6 bilateral neck dissection, followed by postoperative thyrotropin suppressive therapy. There were 42 cases of papillary carcinoma (91.3%) and 4 cases of follicular carcinoma (8.7%). Cervical lymph node metastasis was found in 39 cases (84.8%). In the follow-up period of 1 to 25 years (mean 10 years), no death of thyroid carcinoma occurred. CONCLUSIONS: The most common DTC in adolescents is papillary carcinoma with better prognosis regardless of the higher incidence of cervical lymph node metastasis. The optimal extent of primary thyroidectomy and neck dissection followed by postoperative thyrotropin suppressive therapy in adolescents with DTC may improve the quality of life and decrease the incidence of complications. PMID- 17349177 TI - [Study on the early liver metastasis forecast of colorectal neoplasms]. AB - OBJECTIVE: To obtain some effective objective markers used to predict the early liver metastasis of colorectal tumor, the relationship of liver metastasis of colorectal tumor with associate detection three markers such as CK20mRNA, CD44v6 and VEGF was studied. METHODS: The expression of CK20mRNA in patrol venous blood from 30 colorectal cancer patients was detected by fluorescent quantitative RT PCR, and the results of CD44v6 and VEGF in colorectal cancer tissue were determined by means of immunohistochemistry, and then compared with those in control groups. RESULTS: The rate of positive expression of CK20mRNA in colorectal cancer patients' patrol venous blood was obviously superior to the level of benign pathological changes controls (P < 0.01), and significantly higher than that of normal controls (P < 0.01). The rate of positive expression of CD44v6 and VEGF in colorectal tumor tissue was distinctly superior to the level of benign pathological controls, and remarkable higher than that of normal controls (P < 0.01). The positive expression of liver metastasis was also clearly higher than that of no liver metastasis (P < 0.05). The rate of positive expression of CK20mRNA in patrol venous blood was evidently correlated to the expression of CD44v6 and VEGF in tumor tissue (r(1) = 0.933, r(2) = 0.906, P < 0.05). The results of associate detection of CK20mRNA, CD44v6 and VEGF were closely related to the incidence of liver metastasis. CONCLUSIONS: If combined detecting these markers of CK20mRNA, CD44v6 and VEGF to forecast liver metastasis of colorectal tumor, the sensitivity and specialty of prediction will be improved, there were highly clinical values in predicting in early diagnosis liver metastasis of colorectal tumor. PMID- 17349178 TI - [Appraisal of the repair gastroschisis with autogenous umbilical cord]. AB - OBJECTIVE: To review the treatment of repair gastroschisis with autogenous umbilical cord in 13-year and evaluate its effect. METHODS: Twenty-two newborns who underwent the repair gastroschisis with autogenous umbilical cord between 1992 and 2005. The physical growth, intelligence measuring, area of operation in abdomen in the survived 18 cases were observed and followed-up. RESULTS: Eighteen patients recovered uneventfully, survival rate is 82%, their growth is well. They all developed incisional hernia near the operation, 9 cases recovered himself, 2 cases was operated to repair the abdominal hernia, 7 cases is under observed. CONCLUSIONS: The material is adopted easily in the operating, autogenous umbilical cord is elastic tissue and no toxicity could relax the abdominal press effectively after the operation, the survival rate is high. PMID- 17349179 TI - [Treatment and prognosis of anaplastic thyroid carcinoma]. AB - OBJECTIVE: To investigate the treatment model and the factors that influence survival of the patients with anaplastic thyroid carcinoma (ATC). METHODS: The clinical data of all patients with ATC in our hospital from May. 1970 to May. 2005 were analyzed retrospectively with regard to mortality and survival rate (Kaplan-Meier). Multivariate analysis was performed by the Cox proportional hazard model. RESULTS: Fifty cases together were analyzed. The overall 1-year, 3 year, 5-year survival rate were 39.4%, 29.6% and 20.7% respectively. The median survival time was 6 months. Univariate analysis showed the patients with their age < 55 years old, without distant metastasis, white blood cell count < 10.0 x 10(9)/L at presentation, without receiving chemotherapy, receiving radiotherapy with the dose no less than 40 Gy, receiving multiple modality therapy had a better prognosis. White blood cell count at presentation, the model of therapy were the risk factors independently influencing prognosis by multivariate analysis. CONCLUSIONS: White blood cell count at presentation, receiving surgery and postoperative radiotherapy or not were the risk factors independently influencing prognosis. The prognosis of anaplastic thyroid carcinoma was worse; the patients with ATC maybe get a better prognosis by receiving surgery and postoperative radiotherapy. PMID- 17349180 TI - [Clinical research of synchronous colorectal neoplasms]. AB - OBJECTIVE: To investigate the clinical and pathological features of synchronous colorectal carcinomas and explore the specificity of treatment for those patients. METHODS: A retrospective evaluation of 326 patients with primary colorectal cancer were performed. The patients were divided into two groups: single cases (303 patients) and synchronous cases (23 patients, index cancer and second cancer). Clinical characteristics, routine pathological findings in the two groups were compared statistically. RESULTS: There was no difference in location of the lesions between the single cases and the index lesions of synchronous cases, while the differentiation and Ducke stage of index lesions were better than those in single cases. The secondary cancer of synchronous cases showed better grades and stages than those of single cases. The frequencies of complicating adenoma and multiple polyps in synchronous cases were higher significantly than those in single cases, with the rate of 34.8% and 78.3%, 11.6% and 42.2%, respectively. All malignant lesions were resected radically, and multiple polyps (56.9%) were electro-resected under colonoscopy at 2 approximately 3 months after the carcinomas were radically resected. Of the patients complicated with adenomas, 79.1% (34 cases) were given one-stage local resection or local colectomy and the rest were given second stage electro resection. CONCLUSIONS: For the clinical and pathological features of synchronous colorectal carcinomas, it is essential to perform a complete evaluation of all colorectal lesions, establish an individual surgical treatment and follow-up in time. PMID- 17349181 TI - [Investigation of the role of hepatic oval cell in primary hepatocarcinogenesis using specific Y chromosome]. AB - OBJECTIVE: To determine the role of hepatic oval cell in primary hepatocarcinogenesis using specific Y chromosome. METHODS: The model of hepatic oval cell proliferation was established by feeding 30 male Wistar rats with 0.06% 3'3-diaminobenzidine (DAB) for 4 weeks. Another 40 female Wistar rats were equally randomized into two groups: control group and experimental group. Experimental group was inoculated with oval cells suspension from the prepared male rats under the hepatic amicula and fed with DAB for 14 weeks continuously to promote hepatocarcinogenesis. Control group was fed with DAB for 14 weeks. After primer fragments were worked out on the male rats' SRY genes using the software of primer design, DNAs were extracted from the hepatic carcinomas of the female rats of the two groups and then amplified with PCR. Electrophoretic analysis was performed on the products. RESULTS: After 14 weeks, primary hepatocarcinogenesis was found in the livers of all the 40 female rats. Electrophoresis showed the positive straps from the experimental group with the same length to the designed segments, whereas no positive straps were seen in the control group. CONCLUSIONS: The hepatic oval cells can differentiate into hepatic cancer cells, which provides the evidence that the hepatocellular carcinoma has its source from the hepatic oval cells. PMID- 17349182 TI - [Association between vascular endothelial growth factor gene 936 T/C polymorphism and colorectal cancer together with anastomotic leakage]. AB - OBJECTIVE: To investigate the association between VEGF gene 936 T/C polymorphism and colorectal cancer together with anastomotic leakage. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the VEGF 936 T/C genotypes in colorectal cancer patients and healthy controls. RESULTS: There was no significant difference in the frequency of VEGF 936 C/C genotype or C allele between colorectal cancer patients and healthy controls (P > 0.05). The C/C genotype or C allele in colorectal cancer patients with anastomotic leakage was less frequently found than in the group without anastomotic leakage (P < 0.05). CONCLUSIONS: VEGF 936 C/C genotype or C allele is not related to the development of colorectal cancer, but they can reduce the risk of anastomotic leakage after surgery in colorectal cancer patients. PMID- 17349183 TI - [Preliminary Study of Screening the Related Genes of Gallbladder Cancer with Gene Expression Profiling Chips of Tumors]. PMID- 17349184 TI - [Hepatectomy under Trans-abdominal and Pericardial Total Hepatic Vascular Exclusion of 7 cases ]. PMID- 17349185 TI - [The Development History of Surgery in China (1): 1915-1951]. PMID- 17349186 TI - [A retrospective study of 541 cases with segmental resection of mandible]. AB - OBJECTIVE: To evaluate the epidemiology and treatment of segmental defect of mandible. METHODS: A total of 541 patients were evaluated retrospectively. The character of the mandibular defect and method of reconstruction were analyzed. RESULTS: The majority of segmental defect of mandible were found in 40 - 70 years old males and the leading cause was tumor. The reconstruction methods included soft flap, reconstruction plate and bone grafts. The main complications were infection and fistula. CONCLUSIONS: Tumor was the main cause of segmental resection of mandible, which occurs mainly in adult males. The body of the mandible was often involved. Vascularized bone grafts were the main methods in reconstruction of mandible. PMID- 17349187 TI - [Analysis of postoperative survival rates of mucoepidermoid carcinoma in salivary gland]. AB - OBJECTIVE: The pathologic slides and clinical data of 119 patients with mucoepidermoid carcinoma (MEC) of salivary glands were reviewed. All patients underwent surgical therapy in Department of Oral and Maxillofacial Surgery, College of Stomatology, Fourth Military Medical University. The postoperative overall observed survival rates and specific survival rates were statistically caculated, and the correlative clinicopathologic factors influencing the prognosis were evaluated. METHODS: Statistical analysis was performed using the SPSS 10.0 software. The survival rates were obtained by the Kaplan-Meier method. The clinicopathologic parameters were evaluated using log rank test (univariate analysis) and Cox proportional hazards regression model (multivariate analysis). RESULTS: The overall observed survival rates of this group were 92.53%, 87.52% and 85.39% at 5, 10 and 15 years respectively after surgical therapy. Univariate analysis demonstrated that the factors correlated with lower in survival rates were patient's age (> or = 40 years), advanced clinical stage (TNM III, IV stage) and the poorly differentiated tumors (P < 0.05). The survival rates of male patients with MEC in the major salivary glands were significantly lower than those of female patients (P = 0.008). The degree of differentiation, TNM stage and preoperative symptoms were three important prognostic factors that were selected into the Cox proportional hazards regression model. CONCLUSIONS: Most patients with highly differentiated MEC in salivary glands had a favorable outcome after receiving adequate surgical treatment. The degree of differentiation and the TNM stage of MEC in the salivary glands are two useful factors to evaluate the prognosis of these neoplasms. PMID- 17349188 TI - [The construction and expression of PcDNA3.1(+)/GFP-TIMP-2 in human ameloblastoma cell]. AB - OBJECTIVE: To construct the eukaryotic expression vector of TIMP-2 gene and to explore its expression in human ameloblastoma cell in vitro. METHODS: The aimed gene fragment was obtained by RT-PCR. And then, molecmicrolar cloning technology and enzyme digestion were used to connect the gene with the plasmid PcDNA3.1(+), which can be expressed in eukaryotic cells and a report gene: green fluorescent protein gene (GFP) was already existed in the plasmid. We named the eukaryotic expression vector, which contended our aimed gene TIMP-2 as well as report gene GFP, PcDNA3.1(+)/GFP-TIMP-2. The vector was identified by PCR analysis, EcoR I and Xho I restriction analysis and Sequence analysis. After the PcDNA3.1(+)/GFP TIMP-2 was transfected into cultured human ameloblastoma cell, RT-PCR and Flow Cytometry (FCM) and Microscope wre respectively performed to evaluate the effect of transfection and expression. RESULTS: The constructed vector PcDNA3.1(+)/GFP TIMP-2 was proved correct by enzyme digestion and sequencing analysis. After PcDNA3.1(+)/GFP-TIMP-2 was trasnfected into cultured human ameloblastoma cell, the rate of transfection is 47.6% (Analysis report of FCM), the green fluorescence was found in plasm (observed with fluo-microwave), the expression of TIMP-2 mRNA was elevated 2.4 times compared with the control group. CONCLUSIONS: PcDNA3.1(+)/GFP-TIMP-2 was successfully constructed and it could be transfected into cultured human ameloblastoma cell. It may be benefit to further study of the relationship between the TIMP-2 gene and the behaviour of ameloblastoma. PMID- 17349189 TI - [Clinical effect of the restoration for pathological tooth wear]. AB - OBJECTIVE: To investigate the effect of the restoration for pathological tooth wear. METHODS: A total of 48 pathological weared premolars and molars with restorable space in occlusal surface in 10 patients were restored by composite resins. The patients' masticatory function (biting force, masticatory efficiency, the surface electromyographic (EMG) activity of masseter muscles and anterior temporalis) were compared before and after the treatment. At the same time, the restorations were evaluated according to the modified the United States Public Health Service (USPHS) criterion. RESULTS: After the treatment, patients' clinical syndrome disappeared, the biting force was improved (P < 0.05) and the masticatory efficiency was increased significantly (P < 0.01). EMG activity, the asymmetry index and the action index of the tested muscles during different status had no significant change (P > 0.05). The composite resin restorations of the 48 teeth were all evaluated as A after three month and one year. CONCLUSIONS: Restoring the pathological weared posterior teeth with composite resins is an effective treatment to relieve the patients' syndrome, improve their masticatory efficiency and biting force. PMID- 17349190 TI - [Clinical and experimental study on the reattachment of fractured anterior teeth]. AB - OBJECTIVE: To evaluate the clinical results of three bonding patterns for the reattachment of anterior fractured teeth. METHODS: The reattachment of 59 anterior fractured teeth was performed using three bonding patterns, which were pattern A (pulp chamber concave + labial chamfer), pattern B (pulp chamber concave + lingual notch) and pattern C (pulp chamber concave + lingual notch + labial chamfer), and followed up for more than 24 months. Pattern A, B and C were 14 teeth, 14 teeth and 31 teeth, respectively. Twenty-one sectioned maxillary central incisors (obtained from patients with periodontal disease) whose edge fragments reattached using the three bonding patterns were used for the experimental study of shear bond strength, and each pattern was used in 7 teeth. RESULTS: Three reattached teeth fractured again due to another trauma, two of which was pattern B and one was pattern A. The reattachment of the remaining 56 anterior fractured teeth was successful after a follow up of mean 28.3 months. The experimental study showed that bonding pattern A and C could bear more shear stress than bonding pattern B (F = 5.161, P = 0.017). CONCLUSIONS: The present study suggests that bonding pattern A (pulp chamber concave + labial chamfer) and C (pulp chamber concave + lingual notch + labial chamfer) were the best methods for the reattachment of fractured anterior teeth. PMID- 17349192 TI - [Effect of maxillary protraction in patients with unilateral cleft lip and palate and anterior crossbite]. AB - OBJECTIVE: To investigate the different changes after maxillary protraction between the cleft and non-cleft patients with anterior crossbite. METHODS: Prospective controlled clinical trial was carried out. Eighteen patients (aged 9.6 +/- 1.2 years) with unilateral cleft lip and palate (UCLP) were chosen as the experimental group. Eighteen non-cleft patients (aged 9.8 +/- 1.4 years) with similar malocclusions were selected as control group. All the patients were before puberty according to the evaluation of the hand wrist radiograms. Hyrax appliance and reverse headgear were used in both experimental and control groups. Lateral cephalometric radiographs were taken before and after treatment. Computerized cephalometric analysis was carried out. Paired t tests or t test were performed using software package SAS 8.1. RESULTS: After treatment, the main changes in experimental group were: SNA +1.45 degrees , A-TFH +2.19 mm, SNB -2.18 degrees , ANB +3.64 degrees , MP/SN +2.78 degrees , LL-EP +0.88 mm in UCLP group. And in control group were: SNA +1.42 degrees , A-TFH +2.12 mm, SNB -1.32 degrees , ANB +2.68 degrees , MP/SN +1.47 degrees , LL-EP -1.37 mm. CONCLUSIONS: Before puberty, maxillary protraction could accelerate maxillary forward growth in UCLP patients and the changes were similar to non-cleft patients. The occlusal relationship and soft tissue profile were improved significantly in both patients with or without cleft. The amount of mandibular posterior rotation in patients with UCLP was larger than in those with no cleft. PMID- 17349193 TI - [Cervical vertebral bone age during puberty]. AB - OBJECTIVE: To explore a method for objectively and accurately evaluating cervical vertebral bone age among Chinese growing subjects. METHODS: Using cephalometric and hand-wrist radiographs of 90 boys and 90 girls who were during pubertal period, we measured the third and fourth cervical vertebral bodies and calculated hand bone age using Liaokawa's method. A formula for calculating cervical vertebral bone age was determined by stepwise multiple regression analysis. RESULTS: A method for objectively evaluating cervical vertebral bone age among Chinese growing subjects during pubertal period was established. Y (Y: cervical vertebral bone age) = -20.189 + 24.666X(1) (X(1): AH(4)/AP) +46.468X(2) (X(2): AH(3)/AP(3)) +39.854X(3) (X(3): AH(4)/H) (r = 0.901). The R square of the equation was 0.81. The mean and standard deviation were as follows: constant = 20.19 +/- 4.89 (t = -4.13, P < 0.01), AH(4)/AP(4) = 24.67 +/- 8.32 (t = 2.97, P < 0.01), AH(3)/AP(3) = 46.47 +/- 6.60 (t = 7.04, P < 0.01), AH(4)/H(4) = 39.85 +/- 7.04 (t = 5.66, P < 0.01). CONCLUSIONS: This method could be used to evaluate Chinese growth stages objectively. PMID- 17349194 TI - [Preliminary study on the comparison and analysis of the digital maxillary alveolar casts]. AB - OBJECTIVE: To develop a three-dimensional (3-D) comparison and measuring techniques to analyze changes in palatal forms of the serial maxillary alveolar cast and to evaluate the significance of the different reference change indexes. METHODS: Following digitizing the casts with a 3-D laser scanner and using reverse engineering software Geomagic Studio 7.0 for a pair of 3-D digital maxillary alveolar cast of an infant of UCLP before and after cheiloplasty, a pair of cast surfaces were reconstructed. The reference points and the character lines were extracted. RESULTS: The model coordinate system and the datum planes were established on the basis of reference points extracted. The newly developed analysis technique completed 3-D comparison of palatal forms of UCLP infants before and after cheiloplasty. Distances and volumes changes between the surfaces were determined and expressed graphically. CONCLUSIONS: With establishing the model coordinate system and the datum plane, it is possible to visualize the comparison outcome of the reference change indexes longitudinally. The various reference change indexes may reflect the trend of the infant maxillary growth. PMID- 17349195 TI - [Comparison between genes of highly toxic strain and minimally toxic strain of Porphyromonas gingivalis]. AB - OBJECTIVE: To identify the differential genes in Porphyromonas gingivalis (P.gingivalis) highly toxic strain W83 and minimally toxic strain ATCC 33277. METHODS: Using suppression subtractive hybridization (SSH) to compare P.gingivalis highly toxic strain W83 (tester) and minimally toxic strain ATCC 33277 (driver). The chromosomal DNAs were purified from P.gingivalis W83 and P.gingivalis ATCC 33277, and digested by restriction enzyme RsaI. The tester DNA samples were separated and ligated with adaptor 1 and adaptor 2R. Two subtractive hybridization and PCR profile were performed. Tester-specific DNAs also were selectively amplified. The mixture of subtracted DNA fragments were ligated with pMD-18T vector and transformed to competent cells E.coli JM109. The differential subtraction library was established. The positive clones were identified by PCR and then sequenced, and searched homologically. RESULTS: Subtractive library which had high subtractive efficiency was successfully set up and 36 positive clones were screened by SSH. The fragments from 88 bp to 372 bp were enriched in P.gingivalis highly toxic strain W83 sequences which were absent from P.gingivalis ATCC 33277. Through dot blot analysis confirmed that all these fragments were present in P.gingivalis W83 but absent from ATCC 33277. The GenBank homology search indicated that among them, several genes were associated with two paralogous regions of the chromosome; Some genes are associated with evasion of P.gingivalis W83; Another gene was related to antibiotic resistance and the products of some genes were virulence and acquisition of peptides. CONCLUSIONS: Comparative whole-genome analysis of highly toxic and minimally toxic strains of P.gingivalis has identified the clustering of genes that are present in W83 but divergent in or absent from ATCC 33277. These genes may provide an important clue for studying the mechanism of occurrence and development of periodontal disease. PMID- 17349196 TI - [Experimental study on dog's bone marrow stem cells transfected by pIRES2-EGFP IGF-1 gene]. AB - OBJECTIVE: To establish the bone marrow stem cells (MSC) model which could highly express the insulin-like growth factor 1 (IGF-1) transfected by dog's IGF-1 gene. METHODS: pIRES2-EGFP-IGF-1 was transfected into MSC by lipofectamine. Positive clones were selected with G418. The expression of IGF-1 protein in the MSC was determined by immunohistochemistry and Western blot analysis. The IGF-1 in the supernatant of the transfected MSC was detected by sandwich-in ELISA. The periodontal ligament cells (PDLC) were cultured in the supernatant of the transfected MSC. The changes of PDLC' proliferation were observed by MTT. RESULTS: IGF-1-transfected MSC could apparently express IGF-1. The IGF-1 protein in the supernatant of the transfected MSC was confirmed by sandwich-in ELISA. IGF 1 could promote the PDLC' proliferation. CONCLUSIONS: The MSC transfected by dog's IGF-1 gene can highly express IGF-1, which may lay the foundation for further study on periodontal regeneration. PMID- 17349197 TI - [Mineralization effects of human platelet-rich plasma on human periodontium cells]. AB - OBJECTIVE: To observe the effects of platelet-rich plasma (PRP) on inducing mineralization of human gingival fibroblasts (GF), periodontal ligament cells (PDLC) and alveolar bone osteoblasts (AOB). METHODS: Human whole blood from healthy subjects was collected and PRP was obtained after twice centrifuged. GF, PDLC and AOB established from tissue explants were used at 4th passage in culture. All cells were seeded at density of 4 x 10(7)/L at 6 well tissue culture plate and cultured at standard condition for 96 hours, and then the different media was used. In the experimental group, the cells continued to be cultured in 50 ml/L PRP in DMEM media with mineral solution (10 mmol/L beta-glycerophosphate, 0.2 mmol/L freshly prepared ascorbic acid, 10 nmol/L dexamethasone), in the control group, the cells to be cultured in DMEM media with mineral solution, and in the blank group DMEM media was used. The media was changed every other day until day 30, the cells were dyed with von Kossa. Pictures were taken and analyzed by the image analysis software to semiquantitate the proportion of the positive area of von Kossa dye and attenuation aera of AOB. RESULTS: In PDLC and AOB, the quantity of mineralization nodule in the experimental group and the control group was more than that in the blank group (P < 0.05), and there were more mineralization nodules in the experimental group than in the control group (P < 0.05), while the amount of mineralization nodules in GF was low in the three groups (P > 0.05). Attenuation of AOB in the experimental group was less than the control group (P < 0.05). CONCLUSIONS: PRP can enhance the quantity of mineralization in PDLC and AOB in vitro and reduce attenuation in AOB, which suggests that PRP may be helpful to periodontal alveolar bone mineralization and regeneration. PMID- 17349198 TI - [Effect of simvastatin on residual ridge resorption after tooth extraction]. AB - OBJECTIVE: To observe the effect of simvastatin carried by poly (lactide-co glycolide) (PLGA) on residual ridge resorption following tooth extraction. METHODS: Sixty male Wistar rats were divided into experimental groups and control groups (30 rats/group). PLGA was immediately implanted with or without simvastatin into extraction sockets of the mandibular incisors. Soft X-ray photography, bone mineral density (BMD) and histopathologic study were conducted at 7, 14, 28, 56, and 84 days after implantation. RESULTS: The relative length values of residual alveolar ridge of the experimental groups were greater than those of the controls at 14, 28, 56, and 84 days after implantation, and there was a significant difference between the experimental and control groups (P < 0.05). The BMD of the specific region was higher in the experimental groups [(7.101 +/- 0.025), (7.178 +/- 0.039), and (7.162 +/- 0.052) g/cm(2)] than that in the control groups [(7.074 +/- 0.014), (7.117 +/- 0.012), and (7.059 +/- 0.037) g/cm(2)] (P < 0.05) after 28, 56, and 84 days. Light microscopy showed that bone formation rate and quality of the experimental group were better than those in the control group at the same time. CONCLUSIONS: Simvastatin carried by PLGA could induce bone formation of tooth socket. Local application of simvastatin would be potential to preserve the length and bone volume of alveolar ridge after tooth extraction. PMID- 17349199 TI - [Posttraumatic temporomandibular joint ankylosis: clinical development and surgical management]. AB - OBJECTIVE: To investigate the patterns of condylar fractures associated with temporomandibular joint ankylosis (TMJA) and treatment methods and results based on the different types of ankylosis. METHODS: Forty-two joints of ankylosis in 31 patients with were categorized to four groups according to Sawhney's classification and undergone surgical treatment as follows: a joint release and disc reposition for Type I ankylosis, a dissection of bony block and disc reposition for Type II; a dissection of full-joint and employment of the temporal myofascial flap as interposition for Type III; a radically dissection of full joint followed by ramus distraction osteogenesis and genioplasty for Type IV. All of patients were followed up for 9 to 54 months with an average of 30 months. The range of mouth opening and temporomandibular joint (TMJ) function were assessed. Condylar fractures were retrospectively investigated on the patterns and the course of ankylosis development. Macroscopical visualization on the osseously ankylosed sites and disc displacement were analyzed in comparison with the radiological findings. RESULTS: Condylar sagittal and comminuted fractures were most susceptible to TMJA. Early fibrous ankylosis occurred usually at the 4th or 5th month post-traumatically with an average month opening of 18.3 mm. The articular discs were found displaced in all cases and early bony bridge formed at a limited area where there was no disc as cushion. During fellow-up, considerable improvement in mandibular movement was attained with a stable joint function and mouth opening range of over 30 mm except for two cases in which ankylosis relapsed. CONCLUSIONS: Condylar sagittal and comminuted fractures are most likely to cause ankylosis. Early surgical intervention could reduce the disc and avoid the later ankylosis. PMID- 17349200 TI - [Evaluation of a model of temporomandibular disorders established by transzygomatic arch traction of the mandibular ramus in rabbits]. AB - OBJECTIVE: To evaluate a model of temporomandibular disorders established by transzygomatic arch traction of the mandibular ramus in rabbits. METHODS: Fifteen adult New Zealand rabbits were subjected to traction in the postero-superior direction unilaterally using elastic force and six rabbits used as the control. Histopathologic change of the disc, joint space and cartilage was observed through Hematoxylin and Eosin staining. RESULTS: Anterior disc displacement or disc deformity in four experimental rabbits was observed on the traction side 2 weeks after operation. At 4 weeks, fibrous adhesions in joint compartment were found in five experimental rabbits. The condyles or articular eminences of some experimental rabbits showed irregularities on the cartilage surface. In the 6 th week, bad disc deformity in four rabbits and severe fibrous adhesions in five rabbits was observed on the traction side, and subchondralbone and calcified cartilage became irregular. In control group, All articular structures were normal. CONCLUSIONS: A animal model of temporomandibular disorders can be established by transzygomatic arch traction of the mandible. PMID- 17349201 TI - [Temporomandibular disorders related pain interaction with age, sex and imaging changes of osteoarthrosis]. AB - OBJECTIVE: To investigate the relationship of temporomandibular disorders (TMD) related pain with age, sex and imaging changes of osteoarthrosis (OA). METHODS: All the patients were grouped based on age, sex, imaging changes of OA and TMD related pain. Craniomandibular index (CMI) was calculated for all the patients. RESULTS: TMD related pain was common in females. Significant differences of CMI were existed in all groups under the age of 45 years old. The occurrence of imagine changes of OA was higher in females than in males (P < 0.001). CONCLUSIONS: TMD related pain and imaging changes of OA were more common in females, especially in 16 - 30 years old females. PMID- 17349202 TI - [Quantitative monomolecular coverage of barium glass by the silane coupling agent gamma-methacryloxypropyltrimethoxysilane]. AB - OBJECTIVE: To study the monomolecular coverage of the silane coupling agent gamma methacryloxypropyltrimethoxysilane (gamma-MPS) on the barium glass filler surface. METHODS: Kubelka-Munk (K-M) function values of the isolated OH-groups on the barium glass filler surface, which were based on the change of gamma-MPS concentrations, were measured using the quantitative analysis of the diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy. When all of the isolated OH-groups on the filler surface disappeared (where the K-M function values was zero), the monomolecular coverage of the gamma-MPS molecules on the filler surface was indicated by the linear regression analysis. RESULTS: The relationship tallied with negative linear correlation between the K-M function values of the isolated OH-groups on the barium glass surface and the concentrations of gamma-MPS. Each gamma-MPS molecule occupied 0.21 nm(2) when the monomolecular coverage was formed on the barium glass surface. CONCLUSIONS: The result of this study indicated the optimal amount of silane coupling agent on silanated barium glass filler during the production of resin composite. PMID- 17349203 TI - [Ultrastructure of the taste pores and taste pits of human taste buds]. AB - OBJECTIVE: To observe the ultrastructural features of taste pores and taste pits of human taste buds. METHODS: Three samplers obtained randomly from adults were divided into two perts, and transmission electron microscopy and scanning electron microscopy were used to observe the fine structure of taste buds in human circumvallate papillae. RESULTS: The longer diameter of the taste pores was 1.02 - 7.36 microm, and most of taste pores contained no taste hair and dense material, and the profile of taste pit was triangular. CONCLUSIONS: Taste hair and dense material were seldom observed in most of taste pores. PMID- 17349204 TI - [Present situation of road traffic injury in maxillofacial region]. PMID- 17349205 TI - [Treatment of oral mucosal diseases: part V. Current development in diagnosis and treatment of oral candidiasis]. PMID- 17349206 TI - [The relevance of oral leukoplakia and oral lichen planus to gene single nucleotide polymorphism]. PMID- 17349207 TI - Role of leptin in immunity. AB - Leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection and inflammation and dysregulated immune response in leptin signaling-deficient mice provide strong evidence for the involvement of leptin in the immune responses. Recent data have established the regulatory function for leptin in immunity similar to the function of a pro-inflammatory cytokine, while gene-targeting studies also demonstrated an essential role of leptin in regulating hematopoiesis and lymphopoiesis. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. This review discusses recent advances in understanding the role of leptin in immunity and leptin-signaling pathways involved in modulating immune homeostasis and autoimmune pathogenesis. PMID- 17349208 TI - GATA-3 - not just for Th2 cells anymore. AB - GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A role for GATA-3 during thymic development has long implied by its continuous and regulated expression through out T lineage development, but the absolute requirement for GATA-3 during early T lymphoid commitment/survival previously precluded definitive answers to this question. Several technical breakthroughs have fueled fruitful investigation in recent years and uncovered unexpected and critical roles for GATA-3 in CD4 thymocyte survival, invariant natural killer T cell generation and function, and also in beta selection. Not only does GATA-3 participate in nearly every stage of T cell development from common lymphoid progenitor to Th2, conditional knockout studies have indicated that the influence of GATA-3 also extends beyond the immune system. PMID- 17349209 TI - Nuclear factor-kappaB: activation and regulation during toll-like receptor signaling. AB - Toll-like receptors (TLRs) recognize distinct microbial components to initiate the innate and adaptive immune responses. TLR activation culminates in the expression of appropriate pro-inflammatory and immunomodulatory factors to meet pathogenic challenges. The transcription factor NF-kappaB is the master regulator of all TLR-induced responses and its activation is the pivotal event in TLR mediated activation of the innate immune response. Many of the key molecular events required for TLR-induced NF-kappaB activation have been elucidated. However, much remains to be learned about the ability of TLRs to generate pathogen-specific responses using a limited number of transcription factors. This review will focus on our current understanding of NF-kappaB activation by TLRs and potential mechanisms for achieving a signal-specific response through NF kappaB. PMID- 17349210 TI - TNF-alpha induces transient resistance to Fas-induced apoptosis in eosinophilic acute myeloid leukemia cells. AB - Tumor necrosis factor alpha (TNF-alpha) has been recognized as an activator of nuclear factor kappaB (NF-kappaB), a factor implicated in the protection of many cell types from apoptosis. We and others have presented evidence to suggest that Fas-induced apoptosis may be an important aspect of the resolution of inflammation, and that delayed resolution of inflammation may be directly associated with NF-kappaB-dependent resistance to Fas. Because TNF-alpha activates NF-kappaB in many cell types including inflammatory cells such as eosinophils, we examined effects of TNF-alpha signaling on the Fas-mediated killing of an eosinophilic cell line AML14. While agonist anti-Fas (CH11) treatment induced apoptosis in AML14 cells, no significant cell death occurred in response to TNF-alpha alone. Electrophoretic mobility shift assay (EMSA) revealed that TNF-alpha induced NF-kappaB transactivation in AML14 cells in a time- and dose-dependent fashion, and subsequent supershift assays indicated that the translocated NF-kappaB was the heterodimer p65 (RelA)/p50. Pre-treatment of cells with TNF-alpha dramatically decreased the CH11-induced cell death in a transient fashion, accompanied by suppression of activation of caspase-8 and caspase-3 activation. Inhibition of NF-kappaB transactivation by inhibitors, BAY 11-7085 and parthenolide, reversed the suppression of Fas-mediated apoptosis by TNF alpha. Furthermore, TNF-alpha up-regulated X-linked inhibitor of apoptosis protein (XIAP) transiently and XIAP levels were correlated with the temporal pattern of TNF-alpha protection against Fas-mediated apoptosis. This finding suggested that TNF-alpha may contribute to the prolonged survival of inflammatory cells by suppression of Fas-mediated apoptosis, the process involved with NF kappaB transactivation, anti-apoptotic XIAP up-regulation and caspase suppression. PMID- 17349211 TI - The involvement of heat shock proteins in murine liver regeneration. AB - Partial hepatectomy (PHx) in mammals is a very common experimental model to investigate the process of liver regeneration. The surgery itself could give birth to a series of stresses, such as the temporary raise of body temperature and the ischaemia-reperfusion injury. Heat shock proteins (HSPs) were a family of stress-inducible proteins involved in maintaining cell homeostasis and regulating the immune system. In our study, we intended to investigate the expression and role of HSPs in liver regeneration. Using RT-PCR and Western blotting, we determined the expression in regenerating liver of HSP27, HSP60, HSP70 and HSP90 in mRNA level and protein level, respectively, with mice treated with sham operation as controls. We also used quercertin as an inhibitor of HSPs to explore their effects on liver regeneration. We found that hepatic expression of HSPs increased at the early phase of liver regeneration and declined to the constitutively low level later. Moreover, quercetin pretreatment delayed the progress of liver regeneration in mice via inhibition of HSPs. The results indicated that HSPs played an important role in liver regeneration. PMID- 17349212 TI - Down-regulation of CD44 contributes to the differentiation of HL-60 cells induced by ATRA or HMBA. AB - CD44 is highly expressed in human acute myeloid leukemia (AML) cells. Some experiments had shown that it was possible to reverse differentiation blockage in AML cells by CD44 ligation with specific antibodies, indicating that CD44 was closely related to the differentiation of leukemia cells. The differentiation of acute promyelocytic leukemia cell line HL-60 cells could be induced by all trans retinoic acid (ATRA) and hexamethylene bisacetamide (HMBA), but so far the mechanism was not demonstrated clearly. In the present study, we investigated whether ATRA or HMBA induced the growth arrest of HL-60 cells by down-regulating the expression of CD44. The results indicated that the proliferation of HL-60 cells was obviously inhibited and the differentiation was induced by both ATRA and HMBA. The decreased expression of CD44 and cyclin E mRNA, and the increased expression of p27 and p21 at mRNA levels were observed. Furthermore, there was a negative correlation between the expression of CD44 and p27. It was concluded that ATRA and HMBA played a role in the differentiation induction of HL-60 cells, which was mediated by the down-regulation of CD44, accompanied by down-regulation of cyclin E, and up-regulation of p27 and p21 mRNA. PMID- 17349213 TI - Application of two-dimensional electrophoresis in the research of retinal proteins of diabetic rat. AB - Diabetes mellitus (DM) is a chronic disease which is associated with numerous serious health complications such as diabetic retinopathy, and is the leading cause of new cases of blindness in adults at the age of 20-74 years old. The aim of the study was to establish and optimize a two-dimensional polyacrylamide gel electrophoresis (2-DE) technique for retina proteomics to improve the resolution and reproducibility, and to observe the proteomic changes of retinal tissues in diabetic and normal rats. Proteins were extracted from retinal tissues of normal and 8 weeks diabetic SD rats and used in two-dimensional electrophoresis. Various conditions of retina proteomic 2-DE were adjusted, optimized and protein spots of differential expression were obtained through analysis of 2-DE images with PDQuest software. By choosing appropriate sample amount, using pre-cast IPG dry strips (pH 5-8) and casting 12% equal gel, satisfactory 2-DE images of retina were obtained and a steady 2-DE technique was established. In this way, we found 36 spots in 2-DE gel of diabetic retinas that exhibited statistically significant variations, including up-regulation of 5 proteins in diabetic rat retinas, down regulation of 23, and disappearance of 8, in comparison with normal tissues. The differences of protein expression were observed in retinas between diabetic and normal rats. Our established 2-DE technique of retina proteins could be effectively applied in proteomics of retina diseases. PMID- 17349215 TI - Pacing mode selection in patients with sick sinus syndrome. PMID- 17349214 TI - Cell-mediated immunity imbalance in patients with intrahepatic cholestasis of pregnancy. AB - Decidual lymphocytes may mediate fetal trophoblast recognition and regulate maternal immune reaction and play an essential role in the maintenance of normal pregnancy. The aim of this study was to compare the percentage of T cells, natural killer (NK) cells and natural killer T (NKT) cells within decidual parietalis of normal pregnant controls (NP) and patients with intraheptic cholestasis of pregnancy (ICP), and to investigate the production of interleukin 4 (IL-4), interferon-gamma (IFN-gamma) in the culture supernatant of decidual parietalis mononuclear cells (DPMCs). Compared with controls, the decidua parietalis from ICP were characterized with significant increased percentages of CD3-CD56+ cells, CD3+CD56+ cells, CD56+CD16+ cells, CD56+CD16- cells, CD56+NKG2D+ cells, and the significant decreased percentages of CD3+ cells, CD3+CD4+ cells. There were no differences found for the percentage of CD3+CD8+ cells, CD56+NKG2A+ cells between control and study group. In addition, the enhanced concentration of IFN-gamma was presented in culture supernatant of DPMCs from ICP. It was suggested that the increased NK cells, NKT cells and the decreased T cells in the decidual parietalis and over-secretion of IFN-gamma could be correlated with the pathophysiology of ICP patients. PMID- 17349216 TI - Acid-related disorders and use of antisecretory medication. PMID- 17349217 TI - The global fight against diseases--a race against time. AB - Globalization is the new political theme of our time. But diseases and health problems never respected frontiers; treatment of diseases has for a long time been based on international experience, and health sciences and educations have been part of global networks. The League of Nations' global health organization was founded in 1923, and the successor, WHO, was born even before UN itself. The present and the following issue of the Bulletin, which is an English translation of a series of articles published in a special issue of Ugeskrift for Laeger, the journal of the Danish Medical Association, is different from normal issues, with its focus on the development of global diseases. Here appear the poor, the refugees and displaced, populations with limited access to international medical technology. A clear picture of the threatening perspectives of public health in major parts of the world's populations is drawn, in articles on patterns of development, urbanisation, dominant diseases, particular risk groups, and the need for a stronger effort. With figures, descriptions of trends, and cautious conclusions, the authors demonstrate the massive challenge, calling for empathy, resources, and action. This cannot be solved by proposing political toasts on the blessings of globalization, and charity shows on TV. There is--as traditions demand in health issues--a need for an international, professional effort, based on documentation, professional competence, and well-organized health programmes. PMID- 17349218 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- 17349219 TI - Global health: the ethical responsibility of the pharmaceutical industry. AB - Health as a global issue concerns all and clearly manifests global inequality. All stakeholders of the healthcare systems and disease treatment--including the pharmaceutical industry--have an ethical obligation to contribute to promoting global health. At Novo Nordisk we primarily focus on providing our contribution to global health through defeating diabetes. At the same time we stand by being a private company required to deliver a financial profit, which is why we must create positive results on the financial, the environmental and the social bottom lines. In this article we attempt to provide a brief overview of some of the initiatives that we think business companies can take--and therefore are also obliged to in promoting global health. Further, we have pointed out a number of dilemmas within research and development as well as business ethics that all companies face when they convert the ethical principles to daily practice globally. PMID- 17349220 TI - Health development--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- 17349221 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- 17349222 TI - Global mental health. AB - Mental disorders contribute significantly to the Global Burden of Disease, as four out of the ten diseases with the highest burden are psychiatric. About 25% of all 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 receiving increasing recognition. PMID- 17349223 TI - Global transition in health. AB - "Tempora mutantur et nos in illis" King Lothar I remarked by year 900 AD. What exactly changed in us over time, i.e. how patterns of the epidemiological transition in populations locally and globally might appear, was described by Omran in 1971 [1]. The effect of transition on health and diseases in populations was demonstrated by Frenkl et al in 1991 [2]. And which major public health problems following each other, and why, was underscored by LaPorte in 1995 [3]. In 2000, leaders of the world society decided to identify a range of common goals, the Millennium Development Goals (MDG), to be reached by year 2015. Many of the MDG are directly or indirectly related with the major health problems, particularly those hitting the poorest: lack of clean drinking water, unhealthy environment, high maternal mortality due to lack of care for the pregnant, and lack of control of major communicable, often fatal diseases like child diseases, malaria, HIV/AIDS and tuberculosis. It is remarkable that the specific chronic diseases of major public health relevance are in fact not mentioned in the MDG, even if these diseases increasingly are hitting populations in low- and middle income societies, i.e. developing countries. The world community seems to prioritize the diseases that are most visible, and most often linked with poverty, namely the infectious diseases mentioned above, which together kill about 17 million people annually, often in combination with malnutrition, and the 0.6 million deaths related to birth and pregnancy. With the exception of HIV/AIDS, which also hit richer societies, these diseases of poverty have been under-prioritized regarding research as well. However, at the turn of the Millennium, the burden of "Western" non-communicable diseases was increasing fast in developing countries. And by 2025, the burden of non-communicable diseases is expected to have doubled globally, with half of the burden on developing countries. Therefore it may be rewarding to look backwards upon the three stages of Omran's original thesis on epidemiological transition, to understand life and death forwards, in a world in fast transition, cf. the Danish philosopher Soeren Kirkegaard: "it is true what philosophy tells us, that life must be understood backwards, while not forgetting the second sentence, that it must be lived forwards". PMID- 17349224 TI - Health effects of migration. AB - The proportion of citizens with an ethnic minority background in Denmark is rising and considerations about how to adapt health care services to the needs of this part of the population are becoming increasingly relevant. To do this, knowledge is needed about the factors influencing the health of these population groups. Migration is one of these factors. The process of migration influences the somatic and mental health of migrants and is described in this article. Ethnicity, social position and aspects related to communication also influence migrants' health; however, we do not discuss these factors. PMID- 17349225 TI - Migrants' access to healthcare. AB - Migration means that both locally and globally our world is getting more and more multicultural. From 1975 up to the year 2000, the number of migrants in the world doubled to 175 million, which is 3% of the world's population--half of them living in low-income countries [1]. This figure includes labour migrants, permanent migrants, refugees, and asylum seekers, while undocumented migrants and people who migrate from rural to urban areas are not included. The increasing diversity of the population means new challenges for our societies, including our health services. The aim of this article is to outline a general framework for understanding the access that migrants have to healthcare and the factors that can affect that access. PMID- 17349226 TI - Access to health care for undocumented immigrants: rights and practice. AB - The purpose of this article is to analyse 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. However, in practice, undocumented immigrants in Denmark are able to receive more than emergency health care through unofficial networks of health care providers. PMID- 17349227 TI - Too many chefs in Africa. AB - Available interventions could prevent six out of ten million deaths in children younger than five 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- 17349228 TI - International nutrition and health. AB - Malnutrition is the most important underlying determinant of global disease and death. Maternal undernutrition and too early 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 of the 10 million annual child deaths are due to underlying undernutrition. With rural-urban migration, and access to refined sugar and fat, overnutrition and chronic diseases are becoming an increasing problem, also among the poor. PMID- 17349229 TI - Acute pesticide poisoning--a global public health problem. AB - Acute pesticide poisoning has become a major public health problem worldwide, following the intensification of agriculture and the promotion of agro-chemicals in low and middle income countries, with more than 300,000 deaths each year. The easy availability of highly toxic pesticides in the homes of farming communities has made pesticides the preferred means of 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 the situation. PMID- 17349230 TI - The possibilities for the health sector to actively contribute to peace processes. PMID- 17349231 TI - Socioeconomic correlates of drug use based on prescription data: a population based cross-sectional register study in Denmark 1999. AB - INTRODUCTION: In the public health system we study medical treatment which is ideally provided according to need and independently of economic means. We report use of prescription drugs according to socioeconomic classifications in North Jutland County in Denmark in 1999. METHOD: We conducted a register-based cross sectional study of 385,879 persons aged 18 years or older. Data from the computerized accounting system from the pharmacies were linked with records of socioeconomic status (SES) in the Prevention Registry at Statistics Denmark. We identified all prescriptions redeemed in North Jutland County from 1 January through 31 December 1999 and classified the socioeconomic status for each individual based on the annual registration of income/social benefits, employer, occupation and education. We computed the proportion of persons redeeming at least one prescription and computed weighted averages of prescription proportions for each SES. RESULTS: The highest prevalence of medication use was by persons in early retirement, old age pensioners, people on disability pension and others outside the workforce. We found only minor differences among different economically active groups with slightly more male top managers using cardiovascular drugs. People in the upper half of the socioeconomic scale were somewhat less likely to redeem prescriptions for treating muscle, joints and bone, and central nervous system. CONCLUSION: Social or economic barriers in buying medicine are generally small in Denmark and do probably not provide a likely explanation for the social differences in morbidity and mortality. PMID- 17349232 TI - [Selective parathyroidectomy in sporadic primary hyperparathyroidism]. PMID- 17349233 TI - [Comparison of colostomies and ileostomies as diverting stomas after low anterior resection]. AB - OBJECTIVE: The aim of the present study was to evaluate two procedures (transverse colostomy and ileostomy) as diverting stomas after low anterior resection to determine whether one is superior to the other. MATERIAL AND METHOD: A literature review was performed to compare both stomas from construction to closure. RESULTS: Distinguishing between the complications specific to stoma construction from those caused by anterior resection is difficult. While the stoma is in place, transverse colostomy seems to be better tolerated. Colostomy closure seems to have more septic complications, although the real frequency of bowel obstruction after ileostomy closure remains to be determined. CONCLUSIONS: Given the characteristics of previous studies, the superiority of one diverting stoma over the other cannot be established. Ileostomy seems better tolerated by patients and is associated with a lower complication rate after closure (bowel obstruction remains to be evaluated). Randomized prospective studies with a larger number of patients are required to determine which of these procedures is superior. PMID- 17349234 TI - [Confidence intervals: why use them?]. AB - We analyze the reasons why the use of confidence intervals is highly advisable. Among these reasons, confidence intervals provide an approach to knowledge of the real importance of a result, independently of statistical significance, as well as equivalence assessment between two variables. PMID- 17349235 TI - [Sentinel lymph node biopsy technique in breast cancer surgery in a hospital without a nuclear medical service]. AB - INTRODUCTION: Knowledge of lymph node stage is the most important prognostic factor in breast cancer. The sentinel lymph node biopsy technique (SLNBT), initially developed to avoid unnecessary dissection in melanoma, has been shown to be able to predict the axillary stage of breast cancer. The difficulty of applying the SLNBT in hospitals without a nuclear medicine service has led to the existence of external teams that allow these hospitals to apply the technique. OBJECTIVE: To test the application of the SLNBT in our hospital which has no nuclear medicine service. PATIENTS AND METHODS: Coinciding with the validation of the SLNBT in the Germans Trias i Pujol Hospital in Badalona in November 1999, and with their help, the Centre Hospitalari de Manresa began to apply this technique. In 2002, the technique was used in all the hospitals of the ALTHAIA-Xarxa Assistencial de Manresa. From November 1999 to June 2005, the technique was applied in 163 patients. RESULTS: Of the 163 patients, the technical success rate was 97.55%. In 98% of the patients, the sentinel lymph node was found in the axilla. In 10.7% of the patients, the node was found in the internal mammary basin. Twenty-six percent of the axillas had metastases of over 2 mm, and 16% had micrometastases. One hundred and five patients were spared axillary dissection. CONCLUSIONS: The SLNBT can be performed in a hospital without a nuclear medicine service. This technique improves and simplifies the surgical technique and reduces length of hospital stay and morbidity. PMID- 17349236 TI - [Results of Longo's stapled hemorrhoidectomy in ambulatory surgery for grade III IV hemorrhoids]. AB - INTRODUCTION: We prospectively evaluated the results of stapled hemorrhoidectomy for grade III-IV hemorrhoids in the ambulatory setting. METHOD: Eighty-five consecutive patients with grade III-IV hemorrhoids, treated with the stapled technique with PPH01 in the Ambulatory Surgery Service of the General Hospital of Valencia were studied. Symptomatic, ASA I-II patients who agreed to undergo ambulatory surgery (vehicle, an accompanying adult, address with telephone, elevator, and basic hygiene conditions) were included. RESULTS: Thirty-nine percent were women and 61% were men, with a mean age of 47.6 years. A total of 85.9% had grade IV hemorrhoids and 14.1% had grade III. The average surgical time was 29.81+/- 12 minutes with a mean length of hospital stay of 168.88 +/- 88 minutes. Surgical complications consisted of 16 hemorrhages of the staple line (18.8%) and five hemorrhages due to mucous tear (5.9%). During the first 8 days the most frequent complication was pain (45.9%); only 7.1% of the patients required analgesia with opiates, and one patient required admission for 24 hours for analgesic purposes. Bleeding occurred in 10 patients, five of whom reported slight bleeding on defecation that stopped spontaneously; the remaining five required admission for 24 hours after surgical revision. Nine patients (10.6%) were admitted to the hospital for 24 hours, three due to intraoperative hemorrhage, five due to postoperative hemorrhage and one due to pain. A second intervention was required in 8.2%. CONCLUSIONS: Stapled hemorrhoidectomy can be applied in an ambulatory regime. Although technically simple with a short learning curve, this technique is not free of complications. Suitable patient selection and adequate perioperative information are indispensable for the ambulatory management of this disorder. PMID- 17349237 TI - [Implantation of laparoscopic colon surgery in a general surgery department]. AB - OBJECTIVE: To evaluate the viability, safety and short-term results of laparoscopic colon surgery during the first few years after its introduction in our department. METHOD: Between January 2002 and December 2005, laparoscopic surgery was performed in patients with surgical indication for benign colon disease. After 2003, patients with malignant disease were also included. A database was created and demographic data, surgical indication, technique, conversion rate, morbidity and postoperative length of stay were recorded. All patients were operated on by the same team of three surgeons. RESULTS: Ninety consecutive patients, with a mean age of 59.2 years (20-88) underwent laparoscopic surgery. Of these, 53 were men (59%). In total, 32 patients had previously undergone one or more open laparotomies (35.5%). Surgery was indicated for benign disease in 60 patients (66%). Distribution was left colon in 79 patients and right colon in 11 patients. The most frequent technique was sigmoidectomy (67.7%). The conversion rate was 12.2%. Operating time was 199 min. (120-340) and length of postoperative stay was 7.5 days (4-57). Morbidity was 18.8% and mortality was 1.1%. CONCLUSIONS: Laparoscopic surgery of the colon is safe and reproducible. Our short-term results are similar to those of previous studies. We believe that prior experience of laparoscopic surgery is important and that a stable surgical team minimizes the effect of the learning curve. PMID- 17349238 TI - [Surgical treatment of sclerosing encapsulating peritonitis]. AB - OBJECTIVES: Sclerosing encapsulating peritonitis (SEP) or abdominal cocoon is a rare disease characterized by the formation of a fibrocollagenous membrane that wraps around the loops of the small bowel, producing obstruction. We present the results of the surgical treatment of this disease in three patients with chronic renal failure who developed SEP during the course of peritoneal dialysis (PD) and provide a literature review on the subject aimed at the general surgeon. PATIENTS AND METHOD: In our area, the PD program treated 150 patients in 14 years, with seven cases of suspected SEP. In three patients, exploratory laparotomy was required. Clinical data, diagnostic imaging tests, type of surgery, immediate postoperative course, and status of the patient during subsequent follow-up are described. RESULTS: In one of the three patients, bowel obstruction led to perforation requiring resection with anastomosis; the postoperative course was complicated and the patient died. In the remaining two patients, elective surgery was performed with the aim of removing the capsule enclosing the intestinal loops. In both patients the immediate postoperative course was favorable, although recurrence of intestinal encapsulation occurred in one patient. CONCLUSIONS: The success of surgery in this disease is determined by the technique used. The correct technique consists of freeing the adhesions and extirpating of the capsule as far as possible. Perforation, as well as resection and intestinal anastomosis, significantly increase mortality. PMID- 17349239 TI - [Predictive factors of massive intestinal necrosis in acute mesenteric ischemia]. AB - INTRODUCTION: Suspicion of intestinal necrosis in patients with mesenteric ischemia is mandatory in surgery. Many patients develop massive necrosis after open surgery. However, in some frail, elderly patients, preoperative prediction of massive intestinal necrosis could avoid an unnecessary laparotomy. The aim of this study was to assess predictive factors of massive intestinal necrosis in acute mesenteric ischemia. PATIENTS AND METHOD: We retrospectively evaluated a consecutive sample of 155 patients, 88 men and 67 women, with a mean age of 71.9 years (SD +/- 13.6), who underwent surgery for acute mesenteric ischemia in our institution from 1990 to 2004. Age, sex, clinical features, laboratory findings, and delay to surgery were recorded and assessed as possible risk factors for massive intestinal necrosis. A logistic regression model was used to identify independent prognostic factors. RESULTS: Of the 155 patients, massive intestinal necrosis was recorded in 48 (31%; 95% CI: 23.4-38.6). A statistically significant association was found between massive intestinal necrosis and age (p = 0.04), previous digoxin use (p = 0.01), shock (p = 0.009), hemoconcentration (hemoglobin levels > 16 g/dL) (p = 0.02), hyperamylasemia (p < 0.001), acidosis (p = 0.012), and alkalosis (p = 0.048). Multiple stepwise logistic regression analysis identified three independent prognostic factors that were significantly associated with a higher risk of massive intestinal necrosis: shock (OR = 3.4; 95% CI: 1.1-10), hemoconcentration (OR = 6; 95% CI: 1.6-22.8), and hyperamylasemia (OR = 4.2; 95% CI: 1.5-12.2). CONCLUSIONS: Massive intestinal necrosis can be observed in at least 25% of patients undergoing surgery for acute mesenteric ischemia. Within the limitations of a retrospective study, the variables of shock, hemoconcentration and elevated serum amylase levels may be considered as independent predictive factors of fatal necrosis of the bowel. PMID- 17349240 TI - [Multicentric inflammatory pseudotumor]. AB - Inflammatory pseudotumor is a non-neoplastic process characterized by irregular growth of inflammatory cells. This type of tumor can arise in any part of the body; most are confined to a single site and are benign. We present the case of a 51-year-old man in whom a solitary pulmonary nodule was detected as an incidental finding. Right pulmonary lobectomy was performed and histopathological analysis led to a diagnosis of inflammatory pseudotumor. The patient subsequently developed tumors in the contralateral lung and cervix, the latter being highly aggressive. We found no reports of this association in the literature, prompting the present case report. PMID- 17349241 TI - [Menetrier's disease and gastric cancer]. AB - Menetrier's disease is an infrequent hypertrophic disease of the stomach associated with hypoproteinemia of unknown etiology. This disease is considered to be premalignant since 10-15% of affected individuals develop gastric cancer. We present a 66-year-old patient who had received a diagnosis of Menetrier's disease 13 years previously and who was found to have advanced antral gastric cancer during follow-up. We provide an update on the optimal therapeutic approach, which has not been clearly defined to date. PMID- 17349242 TI - [Immunohistochemistry and surgical approaches in solitary fibrous tumor of the pleura]. AB - Solitary fibrous tumor of the pleura (SFTP) is a rare, benign, slow-growing neoplasm that arises from the submesothelial cells of the pleura. Usually, resection of the tumor and adjacent structures are sufficient for resolution. Nowadays, videothoracoscopy (VTC) allows adequate access for the surgical treatment of these tumors. CD34 antigen positivity is a differential feature with mesothelioma. We present our experience with 15 patients with SFTP (nine women and six men) who underwent surgical resection in the last 12 years (10 thoracotomies, one sternotomy and four VTC). Only four patients were symptomatic at diagnosis. In our opinion, VTC is a less invasive diagnostic and therapeutic approach than thoracotomy that provides an adequate approach for the resection of SFTP in selected patients. Because of the malignant potential of this tumor, long term follow-up is mandatory. PMID- 17349243 TI - [Rupture of a splenic artery aneurysm]. PMID- 17349244 TI - [Surgery in complicated colorectal cancer]. PMID- 17349245 TI - [Surgical approach in carcinoid tumors of the intrahepatic biliary tract]. PMID- 17349246 TI - [Multiple symmetric lipomatosis]. PMID- 17349247 TI - [Anales de Pediatria and the beginning of procedures to include the journal in Journal Citation Reports]. PMID- 17349248 TI - [Energy expenditure in critically ill children: correlation with clinical characteristics, caloric intake, and predictive equations]. AB - OBJECTIVE: To study energy expenditure (EE) in critically ill infants and children and its correlation with clinical characteristics, treatment, nutrition, caloric intake, and predicted energy expenditure calculated through theoretical formulas. PATIENTS AND METHODS: A prospective observational study was conducted in critically ill infants and children. Indirect calorimetry measurements were performed using the calorimetry module of the S5 Datex monitor. Data on mechanical ventilation, nutrition, and caloric intake were registered. Theoretical equations of energy requirement (WHO/FAO, Harris-Benedict, Caldwell Kennedy, Maffeis, Fleisch, Kleiber and Hunter) were calculated. The statistical analysis was performed using the SPSS 12.0 package. RESULTS: Sixty-eight EE determinations were performed in 43 critically ill infants and children aged between 10 days and 15 years old. Measured EE was 58.4 (18.4) kcal/kg/day, with wide individual variability. EE was significantly lower in infants and children who had undergone cardiac surgery than in the remainder. No correlation was found between EE and mechanical ventilation parameters, vasoactive drugs, sedatives, or muscle relaxants. A correlation was found between caloric intake and EE. In a high percentage of patients, predictive equations did not accurately estimate EE. The respiratory quotient was not useful to diagnose overfeeding or underfeeding. CONCLUSIONS: Wide individual variability in EE was found in critically ill infants and children. Predictive equations did not accurately estimate EE. Indirect calorimetry measured by a specific module is a simple method that could allow generalized use of EE measurement in critically ill pediatric patients undergoing mechanical ventilation. PMID- 17349249 TI - [Efficacy of heliox therapy in respiratory insufficiency in infants and children]. AB - OBJECTIVE: To analyze response to heliox therapy in critically ill infants and children with upper and/or lower airway respiratory insufficiency. PATIENTS AND METHODS: Sixty-five patients, aged between 12 days and 8 years old, treated with heliox through facial mask, nasal prongs or non-invasive ventilation were studied. Diagnoses were bronchiolitis (25), upper postextubation respiratory insufficiency (19), respiratory insufficiency after airway surgery (14), and croup-laryngotracheomalacia (7). Response to heliox treatment was measured by the change in clinical scores, respiratory rate, heart rate, pulse oximetry, blood gas analysis, and the need for non-invasive and invasive mechanical ventilation. RESULTS: Fifty-four patients (83.1 %) improved after heliox therapy, with statistically significant differences in clinical score (from 8.7 to 5.5), respiratory rate (from 51.4 to 38.8 rpm), and heart rate (from 161.6 to 145.6 bpm). No changes were observed in saturation or blood gas analysis. After heliox therapy, 29.8 % of patients required non-invasive ventilation and 26.5 % required intubation. Patients with bronchiolitis and those aged less than 1 year had a lesser response to heliox therapy and more frequently required non-invasive ventilation. No significant differences were found in intubation requirements. No adverse effects were observed. CONCLUSIONS: Heliox therapy improved clinical scores in infants and children with upper and lower airway respiratory insufficiency, but a significant percentage of patients needed non-invasive or invasive mechanical ventilation. PMID- 17349250 TI - [Tuberculosis in 0-14 year-olds in Cuba (1994-2003)]. AB - INTRODUCTION: Tuberculosis in infants and children is a sign of continuous transmission. The present article describes the distribution and the trend in incidence rates of new tuberculosis cases in 0-15-year-olds in Cuba. METHODS: Incidence rates and their trend were estimated by provinces and age groups for the 1994-2003 period. Distribution and overall variation percentages, annual average rates, and rates and percentages according to classification were determined. RESULTS: The incidence rate decreased from 0.76 x 10(5) in 1994 to 0.31 in 2003 (59.2% of the overall reduction and 6.6% of the annual average reduction). The highest rate (1.06 x 10(5)) was found in 1995 (26 cases). In almost all provinces, the incidence trend decreased, except in the City of Havana, Sancti Spiritus, Santiago de Cuba, and the Isle of Youth. Childhood tuberculosis was mainly pulmonary (69.6%). Among the affected population, the highest percentages were found in the groups aged 10-14 years (35.6%) and 1-4 years (35.2%). CONCLUSIONS: Tuberculosis is infrequent and is extremely uncommon in infants. Notification is low throughout the country and the overall trend shows a steady decrease. PMID- 17349251 TI - [Nontuberculous mycobacterial lymphadenitis]. AB - OBJECTIVE: To study the clinical features, epidemiology and outcome of nontuberculous mycobacterial lymphadenitis (NTML). METHODS: A retrospective study was performed on 54 patients under 14 years old diagnosed with atypical mycobacterial lymphadenitis between 1987 and 2004. Inclusion criteria were: (i) positive polymerase chain reaction (PCR) test or culture; (ii) positive sensitin skin test 6 mm above Mantoux; (iii) histopathologic features compatible with mycobacterial infection and/or positive direct smear for acid-fast bacilli, Mantoux reaction less than 15 mm, a normal chest radiograph, absence of exposure to an adult with tuberculosis, negative Mantoux test reactions in family members, and exclusion of other causes of granulomatous adenitis. RESULTS: Fifty-four patients were included in the study. The number of NTML cases increased notably from 1996, coinciding with a decrease in cases of tuberculous adenitis. The mean age was 35 months (range: 14 months-6 years). Submandibular nodes were involved in 22 of 63 cases of adenitis (34.9%) and cervical nodes were involved in 21 (33.3%). In 8/42 patients (19%) the tuberculin skin test was larger than 10 mm. Cultures were positive in 52.9% of the cases (18/34) and PCR in 53.3% (8/15). The most frequently isolated mycobacteria was Mycobacterium avium (61%). Therapy failed in 8/21 patients receiving antibiotics (38%), in 10/13 patients with drainage alone (77%) and in none of the patients who underwent surgery (8/8). CONCLUSIONS: Nontuberculous mycobacterial adenitis has become more frequent in our hospital since 1996. Cultures do not always allow isolation of mycobacteria and the Mantoux test frequently yields false positive results, thus hampering diagnosis. The most effective treatment was surgical excision. Nevertheless, when the surgical approach is difficult or there is postoperative recurrence, pharmacological treatment can be useful. PMID- 17349252 TI - [Iodine nutritional status in the school-aged population in Alicante (Spain)]. AB - BACKGROUND: According to the World Health Organization (WHO), goiter is endemic in Spain. The main cause of endemic goiter is iodine deficiency, which is also the principal cause of mental retardation and avoidable cerebral palsy throughout the world. MATERIAL AND METHODS: We conducted an observational study to determine the prevalence of endemic goiter and nutritional iodine status in the province of Alicante. Urinary iodine excretion was measured in a morning urine sample, and thyroid volume was measured by means of a thyroid ultrasound scan. A case of goiter was diagnosed if thyroid volume was above the 97th percentile adjusted by age, as published by the WHO. RESULTS: No cases of goiter were found. In addition, the median urinary iodine excretion levels adjusted by age were within the normal range, as defined by the WHO's criteria. CONCLUSIONS: Endemic goiter was not found in the province of Alicante and urinary iodine excretion values demonstrated adequate iodine intake. Further ultrasound studies are needed to establish reference thyroid volumes for our population. PMID- 17349253 TI - [Insulin glargine in intensively-treated type 1 diabetes mellitus]. AB - OBJECTIVES: To evaluate the use of insulin glargine in intensively-treated children and adolescents. To assess the degree of patient and parent satisfaction with this treatment. PATIENTS AND METHODS: We studied 42 patients with type 1 diabetes. There were 27 girls and 15 boys. The mean age at diagnosis was 6.8 years (range 1.2-13.2), the mean age at initiation of glargine therapy was 12.8 years (range 7.0-17.7), and the mean duration of diabetes was 6.1 years (range 2.0-11.9). Glargine indications were poor metabolic control or frequent hypoglycemia with multiple daily injections of NPH insulin, which were substituted by one dose of glargine. Patient and parent satisfaction with diabetes treatment was assessed with the scale published by Boot. ANOVA, Student's t test, Mann-Whitney and Fisher tests were applied. RESULTS: Variables are reported as mean 6 standard deviation. After 18 months, glargine reduced hemoglobin A1c levels (7.65 % +/- 0.74 vs. 8.03 % +/- 0.69; p = 0.001), with no significant changes in insulin dose (1.03 +/- 0.19 U/kg/day vs. 1.08 +/- 0.21; p = 0.052) or body mass index SDS (standard deviation score) (+0.51 +/- 0.96 vs. 10.61 +/- 1.02; p = 0.11). Glargine also increased patient satisfaction (+44.5 +/ 18.8 points vs. -9.9 +/- 26.8; p < 0.001) and parent satisfaction (+42.0 +/- 17.9 points vs. -20.8 +/- 29.1; p < 0.001) with diabetes treatment. CONCLUSIONS: 1. Glargine insulin improves metabolic control in intensively-treated children and adolescents with type 1 diabetes. 2. Glargine also improves patient and parent satisfaction with diabetes treatment. PMID- 17349254 TI - [Evaluation of formal elements of Spanish pediatrics journals]. AB - INTRODUCTION: Standardization of scientific journals is indispensable for accurate transmission of knowledge, since it guarantees the universality and reproducibility of research. The objective of this study was to evaluate the formal elements of Spanish pediatrics journals. MATERIAL AND METHODS: In 2005, we studied the characteristics of Spanish biomedical journals with special emphasis on Spanish pediatrics journals. The form used for the selection of journals for inclusion in the database Indice Medico Espanol (IME) was employed to evaluate 65 distinct characteristics in each journal. The parameters were grouped in the following five categores: journal presentation, presentation of the articles, scientific and editorial committees, content characteristics, and dissemination parameters. RESULTS: The journals with the highest overall scores were Anales de Pediatria (63 points out of a maximum of 82), followed by Pediatria de Atencion Primaria (53 points), Acta Pediatrica Espanola and Cirugia Pediatrica (55 points each), Pediatrika (53 points), and Revista Espanola de Pediatria (48 points). The score obtained by Anales de Pediatria places this journal in the top 10 Spanish journals included in IME. CONCLUSIONS: Spanish pediatrics journals meet most of the formal elements required of biomedical journals, although some aspects could be improved, such as deficiencies in the frequency and regularity of publication, mention of the dates of manuscript receipt and acceptance, the lack of a clear description of the editorial process of manuscript selection and peer review, the absence of committee members' institutional affiliations, and the absence of articles by non-Spanish authors. PMID- 17349255 TI - [Diabetes mellitus in children and adolescents: chronic complications and associated diseases]. AB - Diabetes is one of the most common chronic diseases. Type 1, or autoimmune, diabetes accounts for more than 95 % of cases in children and adolescents. Chronic hyperglycemia per se is responsible for the development of several microvascular (retinopathy, nephropathy, neuropathy) and macrovascular complications (ischemic heart disease, cerebrovascular disease, and peripheral vascular disease). Other autoimmune diseases are also more frequent in type 1 diabetic patients. The present review aims to provide an update on some recent advances in this field to aid early detection of these complications and prevent or delay their progression through improved metabolic control. PMID- 17349256 TI - [Nephropathy in Schonlein-Henoch purpura: a retrospective study of the last 25 years]. AB - Schonlein-Henoch purpura is a systemic vasculitis due to IgA-mediated hypersensitivity, almost exclusively affecting the pediatric age group. Long-term prognosis is mainly conditioned by renal involvement, which can appear at onset or during the course of the disease. To evaluate renal involvement, 764 patients with Schonlein-Henoch purpura were retrospectively reviewed. Of these, 153 (20 %) had renal involvement, the most frequent form of presentation being non-nephrotic hematuria/proteinuria (67 patients) followed by isolated hematuria (41 patients). Renal biopsy was performed in 39 patients, and the most frequent pathological findings were diffuse mesangial proliferation with IgA deposits and less than 50 % of crescentic glomeruli. Treatment was not curative. Three patients (2 %) progressed to end-stage renal failure and required renal transplantation. One patient died. Notably, two of the patients who underwent renal transplantation had disease recurrence. We stress that nephropathy is usually benign and that it requires long-term follow-up. PMID- 17349257 TI - [Childhood obesity. Recommendations of the Nutrition Committee of the Spanish Association of Pediatrics. Part II. Diagnosis. Comorbidities. Treatment]. AB - The present article reviews the diagnostic criteria for pediatric obesity and its comorbidities. Treatment is also reviewed, including promotion of physical activity, and dietetic, pharmacologic and surgical treatment. PMID- 17349258 TI - [Major histocompatibility complex class II deficiency]. AB - Major histocompatibility complex class II deficiency is an autosomal recessive primary combined immunodeficiency. The prevalence of this deficiency is highest in Mediterranean areas, especially north Africa. Early diagnosis is essential due to high mortality in the first 2 years of life and the possibility of bone marrow transplantation. We report four cases of major histocompatibility complex class II deficiency and describe their epidemiologic and clinical characteristics, diagnostic tests, treatment and outcome. PMID- 17349259 TI - [Gastrointestinal malformations: a cause of chest pain]. AB - Chest pain is an uncommon cause of consultation in childhood and is even less frequent if resulting from digestive causes. We present the cases of two patients with gastrointestinal tract malformations (diverticulum and esophageal duplication cyst) diagnosed after investigation of chest pain. A potential etiology of diverticulum could be a traction effect caused by fibrous adenopathy of tuberculous primary infection. Duplication cysts are inborn defects. Although these malformations are uncommon, clinicians should take them into account in patients with chest pain. PMID- 17349260 TI - [Neonatal sepsis due to herpes simplex virus with fulminant liver failure]. PMID- 17349261 TI - [Absence of evidence is not evidence of absence]. PMID- 17349262 TI - [Prevention of intrauterine hepatitis B virus infection in invasive procedures: a case report]. PMID- 17349263 TI - [Myocardial calcifications in an infant with congenital heart disease]. PMID- 17349264 TI - [Two splenic sequestrations in an infant with homozygous sickle cell anemia]. PMID- 17349265 TI - [Controversies in the diagnosis of pulmonary sequestration]. PMID- 17349266 TI - [Aspiration pneumonia after administration of a polyethylene glycol solution]. PMID- 17349267 TI - [Primary-specialty care referrals in patients older than 7 years]. PMID- 17349268 TI - [Pediatric methadone poisoning]. PMID- 17349269 TI - [Infant hygiene products: the importance of correct labeling]. PMID- 17349270 TI - [Hypopigmented skin lesions and coarse facies]. PMID- 17349271 TI - [Will academic research rescue the drug discovery crisis?]. PMID- 17349272 TI - [Cross-talk between the gut microflora and the host]. PMID- 17349273 TI - [Cell adhesion guides cell polarity]. PMID- 17349274 TI - [Familial pancreatic cancer and the palladin gene: a new look at cancer mechanisms]. PMID- 17349275 TI - [An X-linked lymphoproliferative syndrome (XLP) caused by mutations in the inhibitor-of-apoptosis gene XIAP]. PMID- 17349276 TI - [Shigella flexneri modulates host cell epigenetic information as a strategy to shape the transcriptional response]. PMID- 17349277 TI - [Retinal repair by transplantation of photoreceptor precursors]. PMID- 17349278 TI - [KLHL12/Cullin-3 is a new E3 ubiquitin ligase negatively regulating the Wnt pathway]. PMID- 17349279 TI - [Replication, development and totipotency]. PMID- 17349280 TI - [Hoxa2: a key gene for the facial somatosensory map]. PMID- 17349282 TI - [From nose to brain : a subtle connection]. PMID- 17349281 TI - [IL-23R, a novel susceptibility gene for inflammatory bowel disease]. PMID- 17349283 TI - [On the role played by oxygen in evolution]. PMID- 17349284 TI - [Calreticulin dictates the immunogenicity of anti-cancer chemotherapy and radiotherapy]. PMID- 17349285 TI - [The polarity protein Par-3 regulates myelination]. PMID- 17349286 TI - [Mutations in SYNE-1 lead to a newly discovered form of autosomal recessive cerebellar ataxia]. PMID- 17349288 TI - [Therapeutic agents targetting protein-protein interactions: myth or reality?]. AB - Protein-protein interactions have a key role in transduction pathways that regulate many cellular functions. Structural and functional properties of protein protein interface are now better understood, therefore offering attractive opportunities for therapeutic intervention. Developping small molecules that modulate protein-protein interactions is challenging. Nethertheless, significant progress in this endeavour has been made on several fronts. Here, we use few illustrative examples to summarize recent work in this emerging field. PMID- 17349289 TI - [mRNA-transfected dendritic cells: a promising strategy in immunotherapy]. AB - Dendritic cells play a central role in the initiation of the immune response as they are the only antigen-presenting cells able to prime naive T cells. This makes the dendritic cells the vector of choice to use as a cell-based vaccine in immunotherapy. Although there are several strategies to deliver antigen to dendritic cells, the ones transfected with mRNA coding for tumor or viral antigens are able to induce potent antigen specific T-cell responses directed against multiple epitopes. In this review, we report several advances made in the field of anti-tumoral and anti-HIV immunotherapy using mRNA-transfected dendritic cells-based approaches. PMID- 17349290 TI - [Genetic control of intercellular adhesion or how cadherins shape the fruitfly Drosophila melanogaster]. AB - The beauty and diversity of cell shapes have always fascinated both biologists and physicists. In the early 1950, J. Holtfreter coined the term "tissue affinities" to describe the forces behind the spontaneous shaping of groups of cells. These tissue affinites were later on related to adhesive properties of cell membranes. In the 1960, Malcom Steinberg proposed the differential adhesion hypothesis (DAH) as a physical explanation of the liquid-like behaviour of tissues and cells during morphogenesis. However, the link between the cellular properties of adhesion molecules, such as the cadherins, and the physical rules that shape the body, has remained unclear. Recent in vitro studies have now shown that surface tensions, which drive the spontaneous liquid-like behaviour of cell rearrangements, are a direct and linear function of cadherin expression levels. Tissue surface tensions thus arise from differences in intercellular adhesiveness, which validates the DAH in vitro. The DAH was also vindicated in vivo by stunning experiments in Drosophila. The powerful genetic tools available in Drosophila allow to manipulate the levels and patterns of expression of several cadherins and to create artificially differences in intercellular adhesiveness. The results showed that simple laws of thermodynamics, as well as quantitative and qualitative differences in cadherins expression were sufficient to explain processes as complex as the establishment of the anterior-posterior axis and the formation of the compound eye in Drosophila. PMID- 17349291 TI - [Unfolded protein response: its role in physiology and physiopathology]. AB - The endoplasmic reticulum (ER) is the first compartment in the secretory pathway. In the ER, proteins fold into their native configuration and are modified by post translational modifications. Perturbations that alter ER homeostasis therefore disrupt folding and lead to the accumulation of unfolded proteins. These perturbations include modifications of Ca2+ homeostasis, increased demand for protein folding due to elevated synthesis of proteins in specialized cells or expression of a mutant misfolded protein. To limit accumulation of unfolded proteins, the cells have developed a specialized pathway : the unfolded protein response (UPR). UPR involves the activation of three transmembrane proteins of the ER : the PKR-like ER protein kinase (PERK), the activating transcription factor 6 (ATF6) and the inositol requiring enzyme 1 (IRE-1). The activation of all three components of the UPR depends on the dissociation of the luminal chaperone BiP/GRP78 from the luminal part of these proteins. Once activated, these pathways down-regulate protein synthesis through the phosphorylation of eiF2 (eucaryotic translation initiation factor 2) and up-regulate the transcription of genes which encode ER chaperones, protein folding enzymes and components of the ER-associated degradation system (ERAD). Growing evidences indicate that UPR signaling plays critical roles in nutrient sensing, differentiation of secretory cells such as pancreatic b cell and antibody producing plasma cells, glucose homeostasis and in the development of pathologies linked to accumulation of aggregated proteins. PMID- 17349292 TI - [Molecular genetics of MTHFR: polymorphisms are not all benign]. AB - Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia. Shortly thereafter, we identified the 677C-->T variant and showed that it encoded a thermolabile enzyme with reduced activity. Currently, a total of 41 rare but deleterious mutations in MTHFR, as well as about 60 polymorphisms have been reported. The 677C-->T (Ala222Val) variant has been particularly noteworthy since it has become recognized as the most common genetic cause of hyperhomocysteinemia. The disruption of homocysteine metabolism by this polymorphism influences risk for several complex disorders, including cardiovascular disease, neural tube defects and some cancers. We describe here the complex structure of the MTHFR gene, summarize the current state of knowledge on rare and common mutations in MTHFR and discuss some relevant findings in a mouse model for MTHFR deficiency. PMID- 17349293 TI - [Gene therapy for osteoarticular disorders]. AB - Osteoarticular disorders are the major cause of disability in Europe and North America. It is estimated that rheumatoid arthritis affects 1 % of the population and that more than two third of people over age 55 develop osteoarthritis. Because there are no satisfactory treatments, gene therapy offers a new therapeutic approach. The delivery of cDNA encoding anti-arthritic proteins to articular cells has shown therapeutic efficacy in numerous animal models in vivo. Through the development and the experimental progresses that have been made for both rheumatoid arthritis and osteoarthritis, this review discusses the different gene therapy strategies available today and the safety issues with which they may be associated. Among the different vectors available today, adeno-associated virus seems the best candidate for a direct in vivo gene delivery approach for the treatment of joint disorders. PMID- 17349294 TI - [Netrin-1 and axonal guidance: signaling and asymmetrical translation]. AB - More than 10 years after its initial discovery, netrin-1 - the first described chimioattractive molecule controlling the guidance of the commissural axons - has recently known a unsuspected wave of interest because of its implication in the development of the nervous system but also, more recently, fot its role in angiogenesis and tumorigenesis. Because, of a series of recent publications on netrin-1 signaling, we propose here to describe the recent insight in netrin-1 signaling via its main receptor DCC (deleted in colorectal cancer), and the recent discovery that netrin controls the assymetric distribution of beta-actin in the growth cone. Thus, it seems that netrin-1, but also the neurotrophic factor BDNF, controls acute growth cone responses such as collapse and turning by the regulation of localized protein translation, such as beta-actin. This process involves both transport of beta-actin mRNA, bound to Vg1RBP, to specific locations, and mRNA translation upon stimulation by local activation of the translation initiation regulator eIF-4E-binding protein 1. Indeed, Netrin-1 induces the movement of Vg1RBP granules into filopodia, and triggers a polarized increase in beta-actin translation on the near side of the growth cone before growth cone turning. The binding of BDNF to its receptor Trk has a similar effect for growth cone attraction, althought it is differentially regulated. Thus, this asymetrically synthesized beta-actin may direct actin polymerization and consequently the migration of the growth cone toward the cue. PMID- 17349295 TI - [Home and leisure accidents' mortality]. PMID- 17349296 TI - [Diabetes care in sub-Saharan Africa]. PMID- 17349297 TI - [Neonatal screening: trends, debates and consensus]. AB - This study focuses on the social and political implications of the substantial expansion of genetic tests and neonatal screening. The introduction of neonatal screening for cystic fibrosis is one of the significant developments that have fuelled debate on their appropriateness. It has raised a series of questions on the pros and cons, the role of evidence in biomedicine, and the articulation between the therapeutic approach and foetal selection. In this respect France provides an ideal research field as it was one of the first countries to generalize this screening, launched in January 2002. Several questions arise: What were the terms of the debate in France and their underlying logics? How was consensus reached? More generally, what does this screening tell us about policies on life forms today? PMID- 17349298 TI - [Diffusion of genetic testing in oncology: what criteria for regulation?]. AB - Does gene testing indicate a switch from an histopathological to a molecular approach of human diseases ? Disease management in oncology is already improved by gene testing, at least for some specific cancers. It is however necessary to distinguish the analysis of genes specific to the tumour which gives clues about the fate of the tumours, from those unique to the patients, which gives clues about the future of the person. For the latter so-called germline mutations, wide scale gene-default screening would put pressure on resource allocation from the health care systems of developed countries. Currently the cost of detecting of 700 genes in the whole French population would exceed the whole health budget of the country for the next 10 years. Even if we can anticipate a dramatic decrease in the unit cost of these genetic tests in the future, their diffusion should not be controlled exclusively by technological and market forces. In this paper, we propose to discuss four main parameters for regulating these genetic tests, using as an archetypal example their application to cancer prevention and treatment: (1) which specific cancer disease is targeted by the test (prevalence, incidence, likelihood of cure with current therapeutics, number of years of life potentially saved...); (2) what are the characteristics of the genes tested and which level of evidence is required about the predictive value of the test; (3) what are the size and characteristics of the population who will be offered the test, and (4) which process and public control are necessary before market approval of the test and reimbursement of related expenditures by health care insurance schemes. PMID- 17349299 TI - [Is lung cancer screening by the helical scanner justified?]. PMID- 17349328 TI - Iliorenal bypass: indications and outcomes following 41 reconstructions. AB - Iliorenal bypass is a nonanatomic means of renal revascularization usually performed in high-risk patients. Its efficacy was assessed in this review of 35 patients (17 males and 18 females, two children and 33 adults) ranging in age 8 84 years, who were subjected to 41 iliorenal bypasses at the University of Michigan Hospital during 1975-2003. Renal artery lesions included arteriosclerosis (n = 20), developmental narrowing (n = 10), arterial fibrodysplasia (n = 3), penetrating trauma (n = 1), and aortorenal dissection associated with Marfan disease (n = 1). All patients had hypertension attributed to their renal artery disease. Twenty patients exhibited renal insufficiency (serum creatinine >1.8 mg/dL). Primary reasons for selecting an iliorenal reconstruction over a more conventional open revascularization included advanced aortic arteriosclerosis (n = 9); prior aortoaortic, aortoiliac, or aortofemoral reconstruction (n = 7); a small aortic aneurysm not justifying aortic surgery (n = 6); prior aortorenal surgery (n = 6); congenital abdominal aortic coarctation (n = 4); a hostile retroperitoneum (n = 2); or compromised cardiac status (n = 1). Eleven patients had prior ipsilateral renal artery interventions. Iliorenal bypasses were to the right kidney (n = 20), the left kidney (n = 9), and bilateral (n = 12). Conduits were saphenous veins (n = 29), synthetic prostheses (n = 11), or direct renal artery-iliac artery reimplantation (n = 1). Initial bypass patency was 93%. Follow-up averaged 7.5 years. Three early and six late graft complications resulted in eight secondary operations. The mean preoperative and postoperative serum creatinine of all 35 patients did not vary (1.9 vs. 1.8 mg/dL), although on an individual basis renal function improved in eight, remained stable in 21, and deteriorated in six patients. The series' mean preoperative blood pressure of 180/97 mm Hg decreased postoperatively to 140/78 mm Hg (P < 0.001). Hypertension was cured in three patients, improved in 27, and became worse in four. Antihypertensive medication numbers decreased postoperatively, from a median of three to two (P < 0.0001). Surgical mortality was limited to one patient succumbing from perioperative intestinal infarction. Iliorenal bypass is an effective means of renal revascularization in patients not amenable to more conventional open or transluminal procedures. PMID- 17349329 TI - Surgical management of pancreaticoduodenal artery aneurysms in association with celiac trunk occlusion or stenosis. AB - Aneurysms of the visceral arteries, especially of the pancreaticoduodenal artery, are rare. They show a wide clinical spectrum, ranging from asymptomatic incidental findings to rupture-inducing catastrophic bleedings. Since growth progression and the risk of rupture cannot be foreseen and there is no relation between the size of the aneurysm and propensity to rupture, rupture unfortunately carries a high mortality, >50%. Thus, all aneurysms of the pancreaticoduodenal artery should be treated. The therapy of choice, either operative intervention or catheter embolization, is determined by many factors. Among these are localization, size, relation to other vessels and neighboring organs, the urgency of intervention, and the experience of the therapist. Surgical therapy should be favored in patients with pancreaticoduodenal artery aneurysm due to celiac trunk occlusion. We report here our experience in the surgical treatment of pancreaticoduodenal artery aneurysms in association with celiac trunk occlusion or stenosis over the last 5 years. PMID- 17349330 TI - Carotid endarterectomy in patients with contralateral carotid artery occlusion. AB - The aim of this study was to evaluate the 30-day outcome of carotid endarterectomy in patients with contralateral carotid artery occlusion and compare it to that in patients with patent contralateral carotid artery. We compared 2,959 carotid endarterectomies performed in patients with patent contralateral internal carotid artery to 373 carotid endarterectomies performed in patients with occlusion of the contralateral carotid artery in the same institute between 1988 and 2004. Patient demographics, surgical and anesthesiological strategy, perioperative neurological and cardiac events, and deaths were compared. The patients were grouped and analyzed according to the presence or absence of symptoms and to their gender. No significant difference was shown in perioperative cardiological and neurological events and deaths in patients with contralateral carotid occlusion versus patients without contralateral carotid occlusion. Females had significant more neurological events than males, in both the asymptomatic (P < 0.001) and symptomatic (P = 0.02) groups. Concomitant occlusion of the contralateral carotid artery was not associated with increased risk of perioperative cardiological or neurological adverse events. However, female gender was associated with higher risk for adverse neurological events. PMID- 17349331 TI - Carotid artery aneurysms: Serbian multicentric study. AB - This multicentric Serbian study presents the treatment of 91 extracranial carotid artery aneurysms in 76 patients (13 had bilateral lesions). There were 61 (80.3%) male and 15 (19.7%) female patients, with an average age of 61.4 years. The aneurysms were caused by atherosclerosis in 73 cases (80.2%), trauma in six (6.6%), previous carotid surgery in six (6.6%), tuberculosis in one (1.1%), and fibromuscular dysplasia in five (5.5%). The majority (61 cases or 67%) of the aneurysms involved the internal carotid artery, 29 (31.9%) the common carotid artery bifurcation, and one (1.1%) the external carotid artery. Forty-five (49.4%) aneurysms were fusiform, while 46 (50.6%) were saccular. Twenty-nine (31.9%) cases were totally asymptomatic at the time of diagnosis. The remainder presented with compression in 14 (15.4%) cases, stroke in 11 (12.1%) cases, transient ischemic attack in 33 (36.3%) cases, and rupture in four (4.4%) cases. In cases where the aneurysm involved the internal carotid artery, four surgical procedures were performed: aneurysmectomy with end-to-end anastomosis in 30 (33.0%) cases, aneurysmectomy with vein graft interposition in 20 (22.0%) cases, aneurysmectomy with anastomosis between external and internal carotid artery in eight (8.8%) cases, and aneurysmectomy followed by arterial ligature in three cases. One case of external carotid artery aneurysm also was treated by aneurysmectomy and ligature. Aneurysm replacement with Dacron graft was performed in 29 (31.9%) cases where common carotid artery bifurcation was involved. Two (2.2%) patients died after the operation due to a stroke. They had ruptured internal carotid artery aneurysm treated by aneurysmectomy and ligature. Including these, a total of five (5.5%) postoperative strokes occurred. In two (2.2%) cases, transient cranial nerve injuries were found. Excluding the five patients who were lost to follow-up, 69 other surviving patients were followed from 2 months to 12 years (mean 5 years and 3 months). In this period, there were no new neurological events and all reconstructed arteries were patent. Three patients died more than 5 years after the operation, due to myocardial infarction. Aneurysms of the extracranial carotid arteries are rare vascular lesions that produce a high incidence of unfavorable neurological sequelae. Because of their varied etiology, location, and extension, different vascular procedures have to be used during repair of extracranial carotid artery aneurysms. In all of these procedures, an aneurysmectomy with arterial reconstruction is necessary. PMID- 17349332 TI - Cerebral monitoring of somatosensory evoked potentials during carotid surgery: a review of 100 cases. AB - The purpose of this study was to evaluate immediate and middle-term results of surgical carotid artery revascularization (CAR) with cerebral monitoring of intraoperative somatosensory evoked potentials (SEPs). Between 1998 and 2004, a total of 100 CARs in 86 patients were performed under general anesthesia with SEP monitoring. A shunt was inserted if SEP amplitude decreased by 50% or latency time increased by 10%. Immediate and middle-term results were analyzed retrospectively. The shunt insertion rate was 5%. Two transient ischemic attacks were observed, and one patient died postoperatively due to myocardial infarction. The cumulative stroke and death rate was 1% at 30 days. Intraoperative SEP monitoring with selective shunt placement can be used safely for carotid surgery. Randomized studies will be necessary to determine the respective indications for various cerebral monitoring techniques. PMID- 17349333 TI - Validity of the Hardman index to predict outcome in ruptured abdominal aortic aneurysm. AB - This study assessed the validity of the Hardman index in predicting outcome following open repair of ruptured abdominal aortic aneurysm and whether this scoring system can be used reliably to select patients for surgical repair. Patients undergoing open repair of ruptured abdominal aortic aneurysm in two university teaching hospitals over a 5-year period were identified from a computerized hospital database. Thirty-day mortality was the main outcome measure. Five Hardman index factors were calculated and related to outcome retrospectively. There were 178 patients with a mean age of 73.9 years (range 51 94) and a male to female ratio of 5.4:1. The overall in-hospital mortality was 57.3% (102/178). Univariate analysis of risk factors showed that age >76 years (P = 0.007, odds ratio [OR] 2.34, 95% confidence interval [CI] 1.26-4.37) and electrocardiograghic evidence of ischemia on admission (P = 0.002, OR 3.75, 95% CI 1.57-8.93) were associated with high mortality. However, loss of consciousness (P = 0.155, OR 1.56, 95% CI 0.85-2.86), hemoglobin <9 g/dL (P = 0.118, OR 1.89, 95% CI 0.85-4.22), and serum creatinine >0.19 mmol/L (P = 0.691, OR 1.25, 95% CI 0.42-3.70) were not significant predictors of mortality. Using a multivariate analysis, age >76 years (P = 0.043, OR 2.29, 95% CI 1.03-5.11) and myocardial ischemia (P = 0.029, OR 2.93, 95% CI 1.12-7.67) were again found to be the significant predictors of mortality. The operative mortality was 44%, 46%, 68%, 79%, and 100% for Hardman scores of 0, 1, 2, 3, and 4, respectively. No patient had a score of 5. The Hardman index is not a reliable predictor of outcome following repair of ruptured abdominal aortic aneurysm. High-risk patients may still survive and should not be denied surgical repair based on the scoring system alone. Further evaluation of the risk factors is required to reliably and justifiably exclude those patients in whom the intervention is inappropriate. PMID- 17349335 TI - Long-term results of venous bypass for lower extremity arteries with selective short segment prosthetic reinforcement of varicose dilatations. AB - The long-term benefit of venous bypass has been clearly demonstrated, but procedure feasibility is contingent upon availability of a suitable vein. In this study, we evaluated the outcome of venous bypasses performed by the first author using veins presenting dilatations that were selectively reinforced with a short prosthesis. The purpose was to answer three questions. First, should ectasis be reduced before reinforcement? Second, do hyperplasia and stenosis develop in reinforced zones? Third, do dilatation and rupture develop in unreinforced zones? Twelve patients, including 10 men and 2 women ranging in age from 36 to 77 years (median 68), underwent bypass for peripheral artery disease in seven cases, popliteal aneurysm in four, and prosthetic rupture in one. Ten patients had poor distal runoff. The bypass was femoral-to-popliteal in eight cases, femoral-to infrapopliteal in three, and popliteal-to-popliteal in one. The graft was reversed in nine cases and ex situ devalvulated in three. The number of prosthetic reinforcements used was one in two cases, two in three cases, three in six cases, and four in one case. All but one prosthetic reinforcement were made of polytetrafluoroethylene (PTFE). Bypass occlusion was observed in two cases, including one case observed in the early postoperative period after bypass for limb salvage in a young man in whom distal runoff was limited to a few collaterals and one case that occurred 4 years after a repeat bypass procedure. The other 10 bypasses remained patent throughout follow-up, which varied from 1 to 11 years (median 4). There were three deaths during follow-up. Doppler ultrasound revealed no stenosis in the reinforced zones and no dilatation in the unreinforced zones but demonstrated progressive deterioration of the runoff in 50% of cases. At the last follow-up examination, two bypasses were patent despite poor runoff. Although the number of patients in this series was small, the outcome of venous bypass using reinforced vein grafts appeared clearly better than outcomes of prosthetic bypass reported in the literature. Reinforcement can be easily achieved using a short, thin-walled PTFE prosthesis adjusted to the proper diameter by gentle dilatation using forceps. Unlike most authors, we do not recommend reducing dilatation by resection or oversewing. Reinforced zones did not develop stenosis and unreinforced intermediate zones showed little or no dilatation and no risk of rupture. PMID- 17349334 TI - Open endarterectomy of the SPT segment: an experience. AB - The purpose of the study was to evaluate the results of open endarterectomy in short atherosclerotic occlusions of the SPT segment (superficial femoral, popliteal, and tibioperoneal arteries). Retrospectively, records from July 1999 to June 2004 of patients who underwent open endarterectomy of lower limb arteries were verified; 63 patients with 66 lesions had open endarterectomy of the SPT segment as a primary procedure. At the time of this study, there were 57 patients alive and six dead, with the cause of death being unrelated to the procedure. The patients had a mean age of 71 +/- 10.73 years, and there were 18 females and 45 males. All patients underwent routine follow-up at 1, 3, 6, and 12 months and yearly thereafter. Routine clinical examination and ultrasound were done to assess the outcome. The mean length of endarterectomized superficial femoral artery was 7.42 +/- 3.66 cm (range 2-15). The lesions involved were the superficial femoral, popliteal, and tibioperoneal arteries (SPT segment). The primary cumulative patency rate by means of life-table analysis was 48.8% at 5 years (mean 12.7 months, range 1-60). During follow-up, percutaneous transluminal angioplasty was necessary in nine patients, for a primary assisted patency rate of 85.1% at 5 years. The location of recurrent stenoses after endarterectomy was usually at one of the ends of the endarterectomy site. Once a preferred technique, endarterectomy is now overshadowed by bypass procedures. Our clinical experience suggests that, in a select group of patients with SPT segment occlusions, open endarterectomy is technically feasible and should be used in cases with insufficient vein for bypass grafting. It also can be used as an alternative to allow the long saphenous vein to be reserved for a bypass procedure in the future. PMID- 17349336 TI - Low molecular weight heparin suppresses tumor necrosis factor expression from deep vein thrombosis. AB - Prior investigations have shown that low molecular weight heparin (LMWH) possesses anti-inflammatory properties in addition to its anticoagulant effects. The physiology of this anti-inflammatory mechanism is poorly understood. Experiments were performed to assess the in vivo anti-inflammatory effects of LMWH in a rat model of deep vein thrombosis (DVT). Sprague-Dawley rats were divided into three groups and underwent laparotomy and inferior vena cava (IVC) ligation directly below the renal veins to induce thrombosis. Twenty-four hours later, intraluminal clot was confirmed at repeat laparotomy using an electromagnetic flowmeter and visual inspection. An intravenous infusion of LMWH or urokinase or no infusion (control) was then performed. Subcutaneous LMWH was given postoperatively to the heparin group. Twenty-four hours after the second operation, the animals were killed, the IVC harvested, the cells from the IVC purified, and cytokine measurements done. The LMWH group showed an overall statistically significant decrease in tumor necrosis factor-alpha (TNF-alpha) levels compared to both the control and urokinase groups by analysis of variance (918 pg/mL vs. 1,345 and 1,623, respectively; P = 0.001). To ensure accuracy, individual pairwise comparisons were performed, which also showed statistically significant TNF-alpha suppression by LMWH compared to control (P = 0.015) and urokinase (P = 0.0009). Treatment of DVT with LMWH causes suppression of TNF alpha expression. This may, in part, explain its anti-inflammatory effects. PMID- 17349337 TI - Efficacy of acrylate tissue adhesive as vascular repair and hemostatic material. AB - The objective of the study was to determine the efficacy of utilizing n-butyl cyanoacrylate (NBCA) tissue adhesive glue as a vascular repair and hemostatic material in the closure of vascular wounds using a prospective, animal-based design. The study was performed on the carotid arteries of 22 goats. The experiment was performed on bilateral carotid arteries (44 procedures). In each animal, both carotid arteries were opened by a procedure simulating carotid endarterectomy. On one side, the repair material was conventional sutures; on the other side, NBCA tissue glue was utilized. The main outcome measures were duration of total flow arrest (clamping time), duration of time from start of arterial repair to complete hemostasis after clip removal (repair time), any additional stitches required after repairing either by stitch or by NBCA, and hematoxylin and eosin histopathology preparations. Forty-four simulated carotid endarterectomy and repair procedures were performed in 22 adult goats. The average repair time on the stitch side was 437 sec and on the NBCA side, 169 sec (P < 0.001). The average clamping time on the stitch side was 716 sec and on the NBCA side, 477 sec (P < 0.001). Macroscopic pathological study did not reveal any significant luminal stenosis. Foreign body microscopic changes were similarly present in both the NBCA and stitch groups, with no significant difference. This is a prospective animal-based controlled study looking into the efficacy of NBCA tissue glue as a material for arterial repair in comparison to classical suture repair. NBCA tissue adhesive glue may be of value especially when fast control of bleeding is required. PMID- 17349338 TI - Cyclooxygenase-2 expression and its association with increased angiogenesis in human abdominal aortic aneurysms. AB - Although the mechanism whereby non-steroidal anti-inflammatory drugs may reduce abdominal aortic aneurysm (AAA) development is unknown, one potential route is via inhibition of the cyclooxygenase (COX) enzyme. Despite the fact that evidence from animal models suggests a role for the COX-2 isoform in promotion of AAA development, only very limited data exist on COX-2 expression in human AAAs. Semiquantitative immunohistochemistry for COX-2 was performed on a series of formalin-fixed, paraffin-embedded human AAAs (n = 49). Associated clinicopathological data, including the degree of inflammatory cell infiltration and neorevascularization, were obtained. COX-2 protein was detected in 46 of 49 (94%) human AAAs. Expression of COX-2 protein varied widely between AAAs. COX-2 protein localized to cells in the inflammatory infiltrate with a morphology characteristic of macrophages. COX-2 expression increased with the extent of inflammatory cell infiltration (P < 0.001) and with the degree of AAA neorevascularization (P < 0.001). Logistic regression analysis identified neorevascularization (P < 0.001) as the only significant independent predictor of COX-2 positivity in human AAAs. COX-2 protein is present at increased levels in the majority of human AAAs and is expressed by mononuclear cells in the inflammatory cell infiltrate. Promotion of angiogenesis by COX-2 may play a role in AAA development. PMID- 17349339 TI - Turbulence significantly increases pressure and fluid shear stress in an aortic aneurysm model under resting and exercise flow conditions. AB - The numerical models of abdominal aortic aneurysm (AAA) in use do not take into account the non-Newtonian behavior of blood and the development of local turbulence. This study examines the influence of pulsatile, turbulent, non Newtonian flow on fluid shear stresses and pressure changes under rest and exercise conditions. We numerically analyzed pulsatile turbulent flow, using simulated physiological rest and exercise waveforms, in axisymmetric-rigid aortic aneurysm models (AAMs). Discretization of governing equations was achieved using a finite element scheme. Maximum turbulence-induced shear stress was found at the distal end of an AAM. In large AAMs (dilated to undilated diameter ratio = 3.33) at peak systolic flow velocity, fluid shear stress during exercise is 70.4% higher than at rest. Our study provides a numerical, noninvasive method for obtaining detailed data on the forces generated by pulsatile turbulent flow in AAAs that are difficult to study in humans and in physical models. Our data suggest that increased flow turbulence results in increased shear stress in aneurysms. While pressure readings are fairly uniform along the length of an aneurysm, the kinetic energy generated by turbulence impacting on the wall of the distal half of the aneurysm increases fluid and wall shear stress at this site. If the increased fluid shear stress results in further dilation and hence further turbulence, wall stress may be a mechanism for aneurysmal growth and eventual rupture. PMID- 17349340 TI - Primary leiomyosarcoma of the innominate vein. AB - Primary venous leiomyosarcoma is rare. We report the case of a primary leiomyosarcoma of the left innominate vein, with neoplastic thrombus extending into the left jugular and subclavian veins. The tumor was curatively resected en bloc with anterior mediastinal and laterocervical lymphatics, through a median sternotomy prolonged into left cervicotomy. Primary venous sarcomas may be associated with prolonged survival in individual cases, with curative resection recommended as the standard treatment, in the absence of distant spread. PMID- 17349341 TI - Spontaneous perforation of a nonaneurysmal infrarenal aorta. AB - Spontaneous perforation of a nonaneurysmal abdominal aorta due to a penetrating atherosclerotic ulcer (PAU) is exceedingly rare. We describe the case of a 57 year-old man with a perforating PAU of the infrarenal aortic wall and discuss the clinical presentation, diagnostic pathways, and therapeutic options based on a comprehensive review of the literature. Since a PAU of the aorta can give rise to chronic mild to moderate abdominal or back pain, a computed tomographic scan of the abdomen should be performed in patients with evidence of vascular disease and persistent abdominal or back discomfort. Surgical resection or stent-graft placement is indicated in symptomatic patients or in asymptomatic patients with radiographic signs of progressive PAU. PMID- 17349342 TI - Adventitial cystic disease of common femoral artery. AB - Adventitial cystic disease (ACD) is an uncommon cause of ischemia. The majority of ACD is located in the popliteal artery. Over 49 extrapopliteal locations have been described. We report on a case of femoral artery ACD in a young patient with claudication. The diagnosis was made with duplex ultrasound and confirmed with computed tomographic angiogram. The patient underwent a surgical treatment. One year postoperatively, the patient is active with no claudication. To our knowledge, this is the first reported case of extrapopliteal artery ACD in Canada. PMID- 17349343 TI - Successful descending thoracic aortic aneurysm repair during a twin pregnancy: case report and literature review. AB - A 28-year-old woman in the first trimester of a twin pregnancy presented with a symptomatic descending thoracic aortic aneurysm. We report our experience in managing a descending thoracic aortic aneurysm in this patient. PMID- 17349344 TI - Administration of octreotide for management of postoperative high-flow chylothorax. AB - Chylothorax is a rare complication of adult cardiothoracic surgery that can affect the postoperative course as it can lead to respiratory insufficiency, protein loss, fluid imbalance, and immunodeficiency. We report the case of a 51 year-old man who developed a persistent high-flow chylothorax after replacement of the descending thoracic aorta for an aneurysm. After a week of complete oral intake cessation and total parenteral nutrition, we started administration of octreotide, a somatostatin analog. It led to rapid cessation of chyle production, and the patient was discharged without further complications and chylothorax relapses. PMID- 17349345 TI - Fibromuscular dysplasia of bilateral brachial arteries treated with surgery and consecutive thrombolytic therapy. AB - A 61-year-old female was admitted to our hospital complaining of paresthesia, pain, and intermittent weakness in the right hand. A pulsating mass with bruits had developed on the patient's upper arm. We also noted an absence of radial artery pulsation. The angiographic findings revealed a classic "string of beads" appearance, which involved both brachial and renal arteries. The right brachial artery exhibited an aneurysm, which was filled with thrombus, and the distal radial artery was occluded with thromboemboli. We excised the abnormal brachial artery segment, replacing it with an autogenous reversed saphenous vein conduit. Consecutive thrombolytic therapy was then performed for the treatment of the radial artery embolism. Histological examination revealed that the patient was suffering from medial fibromuscular dysplasia. This uncommon form of fibromuscular dysplasia, which involves both brachial arteries with embolization, can be efficiently treated via surgery and consecutive thrombolytic therapy. PMID- 17349346 TI - Detachable coils for repair of extraparenchymal renal artery aneurysms: an alternative to surgical therapy. PMID- 17349347 TI - The mid-distal deep femoral artery: few important centimeters in vascular surgery. AB - The deep femoral artery is an important artery in lower-limb revascularization. Employing its initial centimeters as either an inflow or an outflow site has been advocated by many authors. The purpose of this work was to highlight the importance of the mid-distal section of the deep femoral artery, underlining its indications and advantages. From January 1998 to December 2004, we performed, at the Misericordia Hospital Vascular Surgery Unit in Grosseto, Italy, 45 bypasses employing the mid-distal deep femoral artery as an inflow or outflow site. Twenty patients (44.4%) had nonhealing ulcers and/or gangrene, while the remainder (25 patients, 55.6%) presented with rest pain or severe claudication. In 41 cases (91.1%), the mid-distal deep femoral artery was used as the inflow site for peripheral bypasses. In four cases (8.9%), the mid-distal deep femoral artery was employed as the outflow site, twice (4.4%) after aortobifemoral branch thrombosis and twice (4.4%), in the same patient, after inguinal prosthetic infection healing. When the mid-distal deep femoral artery was employed as the inflow site, primary and secondary patency at 1 and 5 years were 92.72% vs. 95.20% and 57.39% vs. 72.81%, respectively. We had two early (<30 days) failures (4.4%) in patients with posterior tibial distal anastomosis, which required above-knee amputation. In two cases (4.4%), we had to perform a transmetatarsal amputation. In one patient, after healing of the inguinal prosthetic infection of an aortobifemoral bypass, we employed the mid-distal deep femoral artery both as inflow and as outflow site. This patient required a monolateral above-knee amputation after 5 months. The mid-distal deep femoral artery is a good outflow and inflow site in patients who have previously undergone surgical interventions in Scarpa's triangle, in those having inadequate vein segment, in those with local inguinal healed infection, and in obese patients. The surgical technique is a practical, easy, elegant, and fast procedure, along with being an optimal alternative to reexploration of scarred inguinal tissue. PMID- 17349348 TI - Sizeable carotid body tumor excision by ultrasonic surgical aspirator: a new technical approach. AB - Carotid body tumors (CBTs) are rare neoplasms. Excision is the preferred treatment and is associated with low mortality and morbidity, although rates of cranial nerve dysfunction postoperatively and blood loss are still high. We herein present a case of a huge CBT, Shamblin group 3, managed successfully by the use of the Cavitral Ultrasonic Surgical Aspirator after preoperative superselective embolization. Our goal was to minimize the possibility of cranial nerve injury, blood loss, and vascular reconstruction. Careful preoperative evaluation, management, and intraoperative precision are essential for successful outcomes. Ultrasonic dissection of a CBT allows a precise and energy-controlled approach, minimizing intraoperative complications in such a demanding and delicate operation. PMID- 17349349 TI - Preliminary retrograde visceral artery reconstruction for thoracoabdominal aortic aneurysms. AB - The recent availability of thoracic endografts has expanded the options for treatment of thoracoabdominal aortic pathology. However, disease that involves the visceral aortic segment presents a special challenge due to the need to preserve mesenteric perfusion. We present three patients in whom preliminary retrograde visceral artery reconstruction was used as an adjunct prior to endovascular repair. PMID- 17349350 TI - Transperitoneal approach should be considered for suspected ruptured abdominal aortic aneurysms. AB - Although transperitoneal surgical repair has been the gold standard for patients with a suspected ruptured abdominal aortic aneurysm (rAAA), the retroperitoneal approach and endovascular aortic repair (EVAR) are increasingly being recommended as preferred approaches due to lower morbidity and mortality. To highlight the importance of considering the transperitoneal approach, we present three cases of suspected rAAA, all with a known AAA, who were found to have other significant intra-abdominal pathology at surgery that would have been missed using the other approaches. PMID- 17349351 TI - Ruptured abdominal aortic aneurysm: does trauma center designation affect outcome? AB - Ruptured abdominal aortic aneurysm (RAAA) continues to be a major cause of mortality in the United States. Rapid diagnosis and uncomplicated surgical repair remain paramount to improving survival in this population. We proposed that the addition of an organized trauma service and subsequent improved management of critically ill patients who present with RAAA would positively impact overall mortality. A retrospective analysis was performed on all patients treated for RAAA at Santa Barbara Cottage Hospital for the years 1985-2004. Patients treated before level II trauma center designation (1985-1999) were compared to those treated after the trauma center was instituted. A total of 76 patients were included in this analysis. The two groups were similar with regard to demographics. However, significant decreases in transport time from the emergency department to the operating room and overall 30-day mortality were seen in patients after the trauma center designation. This designation also led to an increase in the number of cases performed per year, centralizing the treatment for these critically ill patients. Institution of a well-prepared and organized service, such as trauma, improved the outcome for patients treated with RAAA, with a particular benefit in the unstable patient. PMID- 17349352 TI - Management of an abdominal aortic aneurysm infected with Campylobacter fetus: a case report. AB - We present a rare case of an abdominal aortic aneurysm (AAA) infected with Campylobacter fetus. The patient presented with abdominal pain and leukocytosis, without a palpable AAA. Computed tomography (CT) of the abdomen showed a 3.1 x 3.0 cm infrarenal abdominal aneurysm with an extra-aortic fluid collection. At surgery, an in situ graft was placed. Intraoperative aortic wall cultures grew pansensitive C. fetus, and blood cultures remained negative. At 9-month follow up, the patient was doing well without complaints. To our knowledge, this represents only the ninth reported case of an AAA with an aortic wall culture positive for C. fetus. PMID- 17349353 TI - Renal function after elective infrarenal aortic aneurysm repair in patients with pelvic kidneys. AB - Pelvic kidneys complicate aortic reconstructions because of increased risk of renal ischemia. Strategies for protection include shunting, cooling, and reliance on collaterals. A review identified two congenital pelvic kidney (not solitary) and five transplanted kidney patients who underwent elective abdominal aortic aneurysm repair. For congenital pelvic kidneys, topical cooling was used in one patient while no preservation was performed for the other patient. Three transplanted kidney patients were shunted, and one had endovascular repair. Postoperative creatinine values were compared to preoperative values. The two congenital pelvic kidney patients had no significant elevation of creatinine postoperatively. The transplanted kidney patient who underwent endovascular repair had no increase in creatinine postoperatively. All transplanted kidney patients who had open repair had significant but transient increase in creatinine postoperatively. Three patients who were shunted intraoperatively had normalization of creatinine. The patient who had persistent elevation of creatinine at discharge was not shunted. Aortorenal shunting or endovascular repair in transplanted pelvic kidney patients maintains renal function. For patients with congenital pelvic kidneys and adequate collaterals, cooling and collateral perfusion is usually sufficient. Though experience is limited, endovascular repair is likely to be superior to open repair in minimizing renal ischemia. PMID- 17349354 TI - Comparison of retavase and urokinase for management of spontaneous subclavian vein thrombosis. AB - Thrombolysis is an essential first step in the surgical management of acute spontaneous axillo-subclavian vein thrombosis (Paget-Schroetter syndrome). During the past decade, Urokinase became the standard thrombolytic agent until temporarily withdrawn from the market. In its absence, recombinant tissue plasminogen activator (r-TPA) was introduced and attained widespread use. A direct comparison of the efficacy of these two agents in this setting has not been published. The goal of this study is to compare thrombolytic agents in the management of acute Paget-Schroetter syndrome. This study is based on a retrospective review of 30 consecutive patients (15 Urokinase, 15 r-TPA) who underwent thrombolysis and surgery for Paget-Schroetter syndrome. Our hypothesis is that thromblysis with Urokinase and r-TPA is equally safe and effective in management of acute axillo-subclavian vein thrombosis. Primary outcome measures include success of lysis, hemorrhagic complications, subclavian vein patency at completion of treatment, resolution of presenting symptoms, and restitution of normal arm function. There were no significant differences in the primary outcome measures: success of lysis, hemorrhagic complication, perioperative bleeding, and subclavian vein patency. Time to completion of lysis was slightly shorter with r TPA (but this did not achieve statistical significance). One patient in each group suffered incomplete lysis of thrombus. One patient in the r-TPA group required transfusion due to surgical bleeding. No patient received transfusion due to thrombolysis-related bleeding. All patients experienced resolution of symptoms and return of arm function. Our findings support the hypothesis that Urokinase and r-TPA are similarly safe and successful for management of spontaneous axillo-subclavian vein thrombosis. Given these results, secondary factors such as cost, availability, and familiarity with the different agents will likely determine the agent of choice. PMID- 17349355 TI - Adjunctive proximal vein ligation with endovenous obliteration of great saphenous vein reflux: does it have clinical value? AB - The risk of clot extension to the deep venous system or pulmonary embolism following endovenous great saphenous vein (GSV) obliteration is possibly related to the size of the proximal GSV. Some practitioners therefore exclude endovenous GSV obliteration for veins greater than an arbitrary size, starting as little as 15 mm. Others provide adjunctive proximal GSV ligation either routinely, or in selected patients with large veins. The clinical value of adjunctive proximal GSV ligation is unknown. A survey of either the American Venous Forum or the American College of Phlebology, selected for their pedagogic or long-time experience with endovenous GSV obliteration. Respondent characteristics included obliteration technique (laser, radiofrequency [RF], or foam sclerotherapy), academic status, surgical training, indication for and frequency of adjunctive proximal GSV ligation, and society membership. The incidence of pulmonary embolus (PE) and deep vein thrombus (DVT) was also tallied. Twenty-one thousand nine hundred sixty five endovenous GSV obliteration cases were reported, 10,290 with a laser (46.8%), 6,275 (28.6%) with RF, and 5,400 (24.6%) with foam. Only two PEs were reported. Of the 34 patients with DVT, at least 11 had only asymptomatic ultrasound evidence of thrombus extension into the femoral vein, and at least five had only calf vein thrombosis. Comparing ligators (7) with non-ligators (15), the only characteristic significantly correlating with adjunctive proximal GSV ligation was whether the respondent had complete general or vascular surgical training; non-surgeons never ligated the saphenous vein (p < .001). There was no difference between outcomes of ligators and non-ligators. Endovenous obliteration of the GSV poses little risk of PE or DVT, no matter what size the proximal GSV. Although these adverse events may be reduced with adjunctive proximal GSV ligation, the results of this study suggest that adjunctive proximal GSV ligation is superfluous in most patients. PMID- 17349356 TI - Medical benefits of a peripheral vascular screening program. AB - We present preliminary results and analysis of a screening program that has been offered at a community-based hospital since July 2004. The program includes a quick carotid ultrasound study, abdominal aortic ultrasound imaging, and measurement of bilateral ankle/brachial indices (ABI). From July 2004 through January 2006, 1,719 patients were screened, including 1,094 (64%) women and 652 (36%) men. The majority of carotid screens were normal; however, 28.9% (497 patients) had 15-40% stenosis, 1.4% (24 patients) had 40-60% stenosis, and 0.3% (six patients) had >60% stenosis. Sixteen patients (1%) had infrarenal aortic dilation (>3 cm), and an abnormal ABI (<0.90) was detected in at least one limb in 100 patients (5.8%). No procedures resulted from carotid screening; however, two patients underwent urgent repair for 9.3 and 7.5 cm diameter abdominal aortic aneurysms. Abnormal ABI in conjunction with symptoms led to arteriography in three patients, one of whom had iliac stent deployment. This nonselective vascular screening program attracted many new patients into the health-care system. The open/endovascular procedure yield was low, but early disease detection was significant, causing numerous patients to be referred for additional testing and risk factor modification programs. These preliminary data suggest that community-based vascular screening programs play a key role in early vascular disease detection and provide the potential for prevention of disease progression while, at the same time, building sustainable business for hospitals and physicians. PMID- 17349357 TI - Pharmacologic risk factor treatment of peripheral arterial disease is lacking and requires vascular surgeon participation. AB - The pharmacologic treatment of the cardiovascular comorbidities in patients with peripheral arterial disease (PAD) can have a profound effect on the outcomes of these patients. Guidelines for the treatment of hypertension, hyperlipidemia, diabetes, and tobacco use have been published by the American Heart Association and American College of Cardiology (AHA/ACC). Patients with PAD are often under treated for these conditions. We sought to evaluate the adherence to these established guidelines in all new patients presenting with PAD to a vascular surgery clinic and delineate the opportunity for vascular surgeon involvement in these treatments. Consecutive new patients with symptomatic, objectively proven PAD (ankle-brachial index < 0.9) were evaluated in a vascular surgery clinic by a staff vascular surgeon. PAD risk factors, pre-visit medications, and prior cardiovascular interventions were recorded. Patients were stratified whether they were receiving appropriate preventive pharmacotherapy and whether they were meeting AHA/ACC goals. In patients without prior cardiovascular history, screening for these conditions was performed. One hundred sixty-seven new patients were evaluated over a 1-year period. Objectively diagnosed PAD included intermittent claudication in 115 (69%) and critical limb ischemia in 52 (31%) patients. Average age was 67.8 years, and 73 patients (44%) were current smokers. At initial evaluation, only 115 (69%) patients reported antiplatelet use. Patients with a recorded diagnosis of hypertension met clinical guidelines in 39 instances (71%). Eighteen patients (20%) with diabetes mellitus had poor glycemic control (Hgb-A1C > 7.0%). Seventeen (19%) of 88 patients with a history of hyperlipidemia were not adequately treated. Vascular surgeon medical interventions resulted in 31% of patients being started on antiplatelet therapy, 29% of hypertension therapies were modified, 19% of established lipid therapy was modified, and lipid therapy was initiated in 20%. A new diagnosis of hypertension was made in 10 cases (6%) and hyperlipidemia in 13 cases (7%). Despite clear guidelines for the medical community regarding cardiovascular prevention, a large percentage of patients with symptomatic PAD presenting to the vascular surgery clinic are not receiving appropriate therapy for their comorbidities or are not meeting the established goals. Vascular surgeons have an important role in promoting vascular health through the systemic prevention of ischemic events. PMID- 17349358 TI - Endovascular repair of a secondary aortoesophageal fistula: a case report and review of the literature. PMID- 17349359 TI - Recanalization of a thrombosed carotid artery following endarterectomy. PMID- 17349360 TI - Spontaneous dissection of the carotid and vertebral arteries: the 10-year UCSD experience. AB - The etiology of spontaneous dissection of the carotid and vertebral arteries without antecedent trauma remains unclear. The goal of this 10-year review was to examine factors regarding presentation, diagnosis, treatment, and outcome for all patients at our institution who were diagnosed with spontaneous carotid dissections (SCD) or spontaneous vertebral dissections (SVD) with no prior trauma history. A retrospective chart analysis was performed involving all discharges from UCSD Medical Center from 1995 to 2005. Patients were selected for inclusion based on the diagnosis of carotid or vertebral dissection with no associated traumatic or iatrogenic cause for their presentation. Characteristics of these patients' medical risk factors, presenting symptoms, diagnostic method and time, treatment, and outcomes were analyzed. A total of 20 patients (10 male, age 44.8 +/- 12.9 yrs; 10 female, age 39.6 +/- 14.9 yrs) were included for study. These patients represented 12 cases of SCD and nine SVD. On presentation, a majority of patients with both SVD and SCD reported headache as their primary complaint while a significantly higher rate of nausea (25% vs. 67%, p < 0.01) was reported in SVD. SVD was associated with a significantly longer diagnostic time (11 hr vs. 16 hr, p < 0.01). The most commonly performed diagnostic exam in both SCD and SVD was magnetic resonance angiography (MRA). Anticoagulation was the primary treatment in 11 of 12 SCD and all nine SVD. One patient with persistent, symptomatic bilateral carotid dissection after anticoagulation was treated with stent placement resulting in unilateral intracranial hemorrhage (ICH). Length of stay was significantly longer in SVD (5 d vs. 7 d, p < 0.02). A significantly higher incidence of persistent neurologic deficits on discharge was seen in SCD (71% vs. 33%, p < 0.02). Radiographic evidence of cerebral infarction on discharge had a stronger correlation with clinical deficits in SCD. Although there were only two cases, those treated with endovascular therapy in the setting of SCD suffered complications related to the intervention. On discharge, there did not seem to be a correlation between persistent neurologic deficits and radiographic evidence of infarction in SVD reflecting that recovery after these episodes may not be predictable based on the appearance of the infarction. PMID- 17349361 TI - Congenital anomalies of the inferior vena cava and left renal vein: implications during open abdominal aortic aneurysm reconstruction. AB - Although uncommon and usually incidental findings on imaging or at operation, congenital anomalies of the retroperitoneal venous system, particularly those involving the inferior vena cava and left renal vein, can be troublesome and dangerous during open repair of abdominal aortic aneurysms (AAA). We have provided a retrospective analysis of our single tertiary institution experience with these anomalies during more than 2400 open AAA reconstructions in an effort to determine if preoperative identification of these vessels decreased venous injury and subsequent morbidity as well as offering a thorough review of the relevant embryology, anatomy, and technical approaches for each specified anomaly for the practicing vascular surgeon. PMID- 17349362 TI - The left renal entrapment syndrome: diagnosis and treatment. AB - A retrospective analysis was performed to review 20 patients with left renal vein (LRV) entrapment syndrome. All cases were diagnosed based on ultrasonography, magnetic resonance angiography, and renal venography. Technical success was achieved in all patients. Transposition of superior mesenteric artery was performed in three cases, transposition of LRV in two, and stent implantation in the LRV in 15. Stent migration occurred in one case, and stent reimplantation was performed. One case suffered from hematoma after transposition of the superior mesenteric artery, and reoperation was performed. Follow-up was made from 6 months to 6 years after the operation. Abnormalities were not found in the urine test of 18 patients and their symptoms disappeared. Two cases still had microscopic hematuria after exercise. All surgical operations are effective for nutcracker syndrome except excessive invasiveness. Stent may be one of the mainstream therapies because of its minimal invasiveness. PMID- 17349363 TI - Preservation of renal function utilizing hypothermic circulatory arrest in the treatment of distal thoracoabdominal aneurysms (types III and IV). AB - Although left heart bypass and hypothermia are often used in the performance of type I and type II thoracoabdominal aneurysms (TAAs), most of these more distal aneurysms are done utilizing the clamp and sew technique. Renal failure occurs between 8.6% to 39% in recent series of patients following surgery for type III and IV TAAs. The purpose of this study was to determine whether the use of hypothermic circulatory arrest in these cases would serve to protect renal function. All patients were operated on using hypothermic circulatory arrest. The kidneys were perfused with cold blood during the procedures, and renal artery bypasses were aggressively used (when stenoses greater than 50% were observed). The series describes 33 consecutive patients with type III and IV TAAs who were operated on utilizing hypothermic circulatory arrest with a core temperature of 15 degrees centigrade. All visceral and renal arteries were individually perfused; 20 patients had bypass grafts of their renal artery stenoses. Although six patients had renal failure preoperatively, only one developed postoperative renal failure. This was the patient who was operated on as an emergency for severe abdominal pain, back pain, and acidosis who was also the only hospital death. Of the remaining five patients with elevated creatinines preoperatively, four had postoperative decrease of the serum creatinine. One patient developed paraparesis and one developed a stroke. The median length of stay was 8 days. Consideration should be given to the use of hypothermic circulatory arrest in type III and IV TAAs for the preservation of renal function and improved overall results. PMID- 17349364 TI - Staged arterial embolization and surgical resection of a giant splenic artery aneurysm. AB - Splenic artery aneurysms (SAAs) are increasingly being diagnosed as incidental findings. Management modalities include operative treatment, percutaneous embolization, laparascopic ligation, and observation. Giant SAAs larger than 8 cm are a rare entity. We report the case of a 78-year-old woman with an 11 cm SAA who underwent successful percutaneous embolization, followed by surgical excision. We discuss the management of this patient and provide a review of the relevant literature. The approach to SAA should remain individualized. PMID- 17349365 TI - The hybrid aneurysm repair: extending the landing zone in the thoracoabdominal aorta. AB - We present two cases of concomitant management of a type I thoracoabdominal aneurysm and an infrarenal aneurysm via laparotomy, open infrarenal aortic replacement, visceral bypasses from the infrarenal graft, and finally endovascular exclusion of the thoracoabdominal aneurysm. While there are other reports of hybrid procedures for patients with preexisting aortic grafts in place or with retrograde visceral perfusion from a native iliac artery for type II thoracoabdominal aneurysm, these are the first reported cases of concurrent management of a type I thoracoabdominal aneurysm and an infrarenal aneurysm using the infrarenal graft as a distal landing zone for the thoracoabdominal endograft. PMID- 17349366 TI - Surgical repair of an aberrant splenic artery aneurysm: report of a case. AB - Aneurysms of the splenic artery are the most common splanchnic aneurysms. Aneurysms of a splenic artery with an anomalous origin from the superior mesenteric artery are however rare, with eight previously reported cases. Their indications for treatment are superposable to those of aneurysms affecting an orthotopic artery. Methods of treatment of this condition include endovascular, minimally invasive techniques and surgical resection. We report one more case of aneurysm of an aberrant splenic artery, treated with surgical resection, and preservation of the spleen. PMID- 17349367 TI - Surgical management of giant superior mesenteric artery aneurysm. AB - The superior mesenteric artery (SMA) is an uncommon location of aneurysm formation. This entity is potentially lethal and should be treated once a diagnosis is made. When the aneurysm reaches a large size, there is a high risk of rupture and surgical treatment should not be delayed, although it can be technically demanding because there is a significant portion of bowel at risk for ischemia. Here, we describe our approach for the management of a giant SMA aneurysm. PMID- 17349368 TI - Late infected pseudoaneurysm formation after uneventful iliac artery stent placement. AB - Percutaneous transluminal angioplasty and endovascular stent placement are becoming common techniques for iliac artery stenosis and obstruction that are intended to reduce the need for surgical bypass procedures. The usual complications include acute or subacute thrombosis, distal embolization, dissection, and extravasation. Although stent infection is very rare after stent replacement, it is reportedly associated with a high risk of morbidity and mortality, and the use of prophylactic antibiotics should be considered. We present a case of rupture of an infected pseudoaneurysm at the site of the external iliac artery that occurred 4 months after an uneventful percutaneous transluminal angioplasty and stent placement. PMID- 17349369 TI - Treatment options for primary infected aorta. AB - A 71-year-old man, with a history of anterior-perineal bowel resection for previous malignancy, presented with a septic picture and back pain. Investigations revealed a primary infected aorta. At laparotomy an ileocolic tumor was also discovered and resected. Blood cultures prior to the operation were positive for Escherichia coli, and Enterococcus faecium was cultured from the actual aorta. PMID- 17349370 TI - Fungal infection of aortoiliac endograft: a case report and review of the literature. AB - Infection of aortoiliac endografts is, to date, a rare complication of endovascular surgery. Staphylococcus species are the most common responsible pathogens, just as in cases with infected grafts after open aortic surgery. We report a case of a 65-year-old man with a history of diabetes mellitus and bladder cancer who developed stent-graft infection 3 years after endovascular treatment for a 5.6 cm abdominal aortic aneurysm. The diagnosis of endograft infection was established radiologically by computed tomographic scans. After intravenous administration of antibiotics and fluids to improve his clinical condition, the patient underwent surgical excision of the infected prosthesis and a bifurcated rifampicin-impregnated Dacron graft was placed in situ. Cultures from the purulent fluid around the aorta and from the endograft revealed development of Candida albicans. To our knowledge, this is the first case of an infected endograft due to a fungus. The patient died from septic shock 3 days postoperatively in the intensive care unit. PMID- 17349371 TI - Major arterial involvement and review of Behcet's disease. AB - Behcet's disease was first defined by Hulusi Behcetin 1937 as a multisystemic disorder with characteristic pathologic findings including recurrent orogenitalulcers, vascular disorders, and ocular and cutaneous lesions. The disease is mostly encountered at the third and fourth decades of life and especially prevalent in Mediterranean and Far East Asia.Behcet's disease may have both venous and arterial manifestations. The arterial form is rare but it is bore with its manner and to consider recurrent surgical treatments. In this retrospective study, we reviewed the literature related to Behcet's disease and discussed in respect to vascular involvement and the prognosis of surgical treatment.Thirty-one consecutive patients with vasculo-Behcet's disease visiting the departments of cardiovascular surgery, dermatology, and internal medicine in Medical Faculty of Istanbul have been reviewed retrospectively. All available clinical,pathologic, and postoperative data were reviewed and analyzed. Venous system pathologies were present in 15 patients. The pathologies in the remaining patients were related to the arterial tree. Ten patients with aneurysms and/or pseudoaneurysms and six patients with occlusive lesions have undergone surgical treatment. Pseudoaneurysms occurred in six patients at least twice or more. Vascular manifestations are the main predictors of mortality and morbidity in Behcet's disease. Arterial complications may lead to difficult surgical problems.Any invasive methods to arterial system may cause pseudoaneurysms. Repairs by using autogenous veins or synthetic grafts may lead to anastomotic false aneurysms. Surgical treatment should not to be applied in the acute phase of the disease and systemic therapy including colchicine, aspirin,and corticosteroids should be considered for all patients. PMID- 17349372 TI - Extra-anatomical reconstruction in the case of an inaccessible groin: the axillopopliteal bypass. AB - Axillopopliteal bypass is a relatively unknown and uncommon therapeutic option for patients with critical limb ischemia in the presence of an inaccessible groin due to infection or excessive scar formation. In our center, this procedure is performed several times a year. The results of all axillopopliteal bypass reconstructions over an 11-year period were analyzed. Thirty axillopopliteal bypass grafts were performed on 24 patients (16 men, mean age 67 years). In 23 limbs, the indication was persistent groin infection after previous vascular surgery and a threatened limb. In seven limbs, the possibility to anastomose in the groin was absent. There were eight patients (27%) with diabetes mellitus, hypertension was present in 43% (n = 13), and 90% (n = 27) were current or previous smokers. During 5 years of follow-up, 11 patients died, eight during the first year after operation. The primary patency after 1 year was 64% (n = 9). The secondary patency after 1 year was 77%. Seven amputations (23%) were needed: six for ischemia and one for persistent infection. Limb salvage after 1 year was 84%. A limitation of the study is the small number of patients, which was not enough for uni- and multivariate risk analyses with sufficient statistical power. The results of axillopopliteal bypass surgery in patients with critical limb ischemia and an inaccessible groin demonstrate a high mortality rate of 29% after 1 year. However, surviving patients may benefit from the operation in terms of limb salvage because the primary patency was 64% and the secondary patency 77% at 1 year follow-up. We conclude that extra-anatomical axillopopliteal bypass is a valuable therapeutic option for limb salvage in this specific patient population. PMID- 17349373 TI - Treatment of incompetent vein of Giacomini (thigh extension branch). AB - Most varices secondary to truncal insufficiency arise from the greater saphenous vein (GSV), short saphenous vein (SSV), or accessory saphenous branch. However, an important etiology for varices that arise on the posterior thigh or calf is often overlooked. The thigh extension (TE) branch, also known as the vein of Giacomini in many patients, may also contribute to venous pathology. Patients were assigned to one of three categories depending on the anatomical findings. All patients were treated with a combination of endovenous ablation using a 940 nm Skin Pulse S laser and foam sclerotherapy. Eighteen patients were treated and followed for at least 2 years. There were no complications. All patients had successful ablation of the TE branch with successful obliteration of any perforators or collateral vessels. Varices secondary to TE branch insufficiency are common when coexisting SSV insufficiency is present. The incidence increases when both SSV insufficiency and GSV insufficiency exist. This study groups the pattern of TE branch pathology into three anatomical patterns. Combination therapy based on the prevalent anatomical group being treated was done. There was successful ablation in all groups with no complications. As experience in venous disease and expertise by the surgeon increases, more examples of this pattern of pathology will become evident. PMID- 17349374 TI - Atherosclerotic sonographic markers and central cardiovascular status. PMID- 17349375 TI - [Wrist prostheses]. AB - The indications and the complications of the total wrist prostheses limited its diffusion. The complexity of the wrist joint improve the conception of the implant who respected the biomechanics. The experience and the follow-up are too short. All implants respect the wrist biomechanics, but the carpus' fixation is the main cause of loosening. PMID- 17349376 TI - [Short-term results of the IPP 2 proximal interphalangeal joint prosthesis]. AB - INTRODUCTION: The most commonly used type of proximal interphalangeal joint prosthesis is a silicone spacer. A variety of other types of prosthesis have been used over the years. The originalty of our new prosthesis lies in its mode of bone anchorage; namely osseointegration. DESCRIPTION OF PROSTHESIS AND OPERATIVE TECHNIQUE: Two titanium covered screws are inserted in the medullary canals of the proximal and middle phalanges. A connecting hinge allows movement from 0 degrees to 100 degrees. Implantation can be performed without the need for specialised instrumentation. A preoperative template allows the size of screw to be determined in advance. RESULTS: Twenty-eight prostheses were implanted of which 24 were reviewed at a minimum follow up interval of 3.9 years. The diagnosis was primary osteoarthritis in 13 cases and 6 cases were secondary to trauma. Six of the 21 surviving prostheses had a mean follow up period of 6 years (5-14) and 15 a mean of 3 years (2-4). The mean range of movement was -12/55 degrees preoperatively and -9/77 degrees postoperatively. Three patients underwent revision surgery. There was condensation of bone around the proximal screw discernable after 6 months. There were no visible changes in the middle phalanx. The prosthesis did not subside into the proximal phalanx. DISCUSSION: Osseointegration has only recently been taken up in orthopaedics as a means of bone anchorage. In our experience the IPP2 prosthesis had excellent integration in all cases and to date there has been only one hinge breakage. PMID- 17349377 TI - [Patient information in carpal tunnel release]. AB - Patients must be informed of the benefits and risks before any surgical procedure. This information must be clear, honest, specific and complete in order that the patient can give his or her informed consent. This information has to be given face to face, however paper may be used to emphasize certain points and aid retention of information. We studied information sheets for carpal tunnel release given out in ten different hand surgery centres. Different points were identified to analyse each form. From this analysis, a literature review and recent law texts, we propose a new information sheet for carpal tunnel release. PMID- 17349378 TI - [Dynamic biomechanical study of a new osteosynthesis system for distal radius fractures]. AB - The aim of this study was to evaluate the stability in compression of a new implant for fractures of the distal radius. Of all the displacements found with this fracture, shortening is the one most difficult to maintain by osteosynthesis. We tested the properties of a central-medullary steel nail 9 cm length, of diameter 5 mm, curvilinear, introduced at the radial styloid, combining proximal unicortical and distal bicortical locking. The biomechanical laboratory tests were carried out on 10 human radii taken from 5 male anatomical subjects of ages ranging from 48 to 88 years. A wedge-shaped defect in the metaphyseal zone was created to reproduce posterior shortening in these Pouteau Colles' fractures. The same anatomical subject received the two types of osteosynthesis: an intramedullary nail and a styloid pinning. The force displacement curves showed that intramedullary osteosynthesis with this interlocking nail is an assembly three times more resistant to compression than bi-styloid pinning. Stabilization of this fracture in porotic bone has to rely on distal screw purchase in the subchondral bone, which seems to us to be the only element able to resist compressive forces. This new implant should make it possible to restore and preserve the length of the radius whilst maintaining reduction in all three dimensions. Given its good biomechanical results, this nail constitutes a viable possibility for minimally invasive internal fixation of these fractures and warrants a clinical trial. PMID- 17349379 TI - [Bone lengthening by distraction of the metacarpal or phalanx in children]. AB - We report the results of bone lengthening using progressive distraction performed for congenital hand deformities in 12 children between 1998 and 2004. The series is retrospective. Patients were aged between 2 and 11 years. The distraction site was metacarpal in 9 cases and phalangeal in 3 cases. The Mondeal micro distraction device was used. The lengthening procedure was a callotasis with a 0.25 to 0.5 mm/day distraction pace in all cases. The final mean lengthening was 16 mm, and the mean treatment duration was 107 days. The complication rate was 33%. The distraction procedure is described in detail. It is feasible in very young patients as a micro distraction device is used. Family education may prevent complications. This therapeutic procedure gave functional improvement without impairment of distal sensitivity. PMID- 17349380 TI - [Medial epicondyle fractures in children]. AB - INTRODUCTION: Medial epicondylar fractures account for 11% of elbow injuries in children. It represents a Salter-Harris type I lesion. Diagnosis is difficult but on the whole, results are satisfactory. The treatment of this fracture is controversial. PATIENTS AND METHODS: Our study looked at fifty-nine patients between 7 and 14 years old. The main mechanism of injury in our study was a fall (98%). The significance of the fracture displacement was judged according to the classification of Marion and Faysse. We noted 10 cases of stage II, 14 cases of stage III and 35 cases of stage IV according to their classification. Forty-one patients were treated by surgical fixation. Fifty patients were reviewed at an average of six years follow up and the results evaluated according to the criteria of Hardacre. RESULTS: The result was good in 95% of those cases with conservative treatment and in 80% of those cases with operative treatment. Prominence of the medial epicondyle and limitation of elbow motion were the main complications. DISCUSSION: According the literature, a sports accident is the most frequent cause of the injury. The results are better with conservative treatment because there is no relation between fracture displacement and final results. The excellent results of conservative treatment permit us to recommend this method except in those cases with a persistent intra-articular fragment or neurovascular complication. PMID- 17349381 TI - [Madelung deformity: isolated ulnar wedge osteotomy]. AB - OBJECTIVES: Madelung deformity is defined as a partial closure of the medial half of the distal radial growth plate, with anatomical consequences (wrist deformity), and functional impairment (decrease range of motion, loss of grip strength, and wrist pain). We report a new surgical procedure including a shortening of the ulna combined with slight anterior flexion osteotomy aiming to correct the radio-ulnar dislocation and to improve the range of forearm rotation, without correcting the global deformity. METHODS: This was a retrospective study of four symptomatic wrists in three patients. The follow-up was 24 months. Patients were assessed clinically and radiologically pre and post operatively. The ulnar shaft was shortened and anteriorly flexed through a dorsal and ulnar approach and fixed with a fitted internal DCP plate. The aim of this osteotomy was to reduce the dislocated distal radio-ulnar joint. RESULTS: At 24 months follow-up, the function was considerably improved with a correction of the ulno carpial conflict. The range of painfree forearm rotation improved. The post operative views showed a correction of the dorsal dislocation of the ulnar head. CONCLUSION: This technique seemed to be safe and demonstrated good results in these four wrists. It should be proposed in patients with Madelung deformity and assessed prospectively. PMID- 17349382 TI - [Failure of initial surgical treatment of a giant cell tumor of the capitate and its salvage: a case report]. AB - Giant Cell Tumors are rare tumors in the young adult and localisation in the hand is even more exceptional. In the absence of adjuvant treatment, the literature reports a strong potential for local recurrence of between 75 and 86%. These tumours also have a risk of sarcomatosis degeneration and pulmonary metastasis. The case report concerns a 24-year-old patient, with a Giant Cell Tumour of the capitate initially diagnosed on simple curettage, and we describe her treatment together with the treatment of a subsequent reccurrence. A literature review will also highlight the current knowledge of this disease. PMID- 17349384 TI - [Elbow arthroscopy: intra-articular pathologies.] AB - Elbow arthroscopy has become to be the most useful tool for the treatment of many intra-articular affections of the elbow. Radiological statement is necessary including plain radiographs and CT or MR arthrography before performing arthroscopy. Loose bodies are the more frequent indication, they are often related with an other intra-articular pathology. The others indications for an elbow arthroscopy can be, osteochondritis dissecans, synovial fringe, synovitis especially rheumatoid arthritis and arthritic elbow. The treatment of this different pathologies is discribe keeping in mind the potential risks especially neurological. PMID- 17349385 TI - [Arthroscopic Management of the Stiff Elbow.] AB - Elbow stifness has diverse etiologies, the most common being post-trauma. It appears that both arthroscopic and open techniques can achieve satisfactory results when employed properly. Their use is dictated both by the surgeon's level of expertise and an accurate preoperative assessment. When the release is done arthroscopically, collateral ligament stability is not compromised and morbidity from surgical dissection is minimized. The technique of arthroscopic release is described with all steps and difficulties. Arthroscopic capsular release is a technically demanding procedure that requires meticulous attention to detail and should only be attempted by surgeons with extensive experience in elbow arthroscopy. PMID- 17349386 TI - [Arthroscopic treatment of acute elbow fractures.] AB - Surgical management of the rare thrue articular fractures of the elbow remain difficult: the surgeon must achieve anatomical reconstruction with a reliable fixation allowing mobilisation of the joint for early rehabilitation. Arthroscopic treatment of elbow fractures (capitellum, coronoid, olecranous and radial head) gives an excellent intra articular view with few soft tissue damage. Cartilage damage, intra articular loose bodies and capsulolabral injuries are then well adressed. Arthroscopic management of elbow fracture is potentially dangerous for the neuro-vascular structures and requiere good knowleges in elbow arthroscopic technique. We routinely use lateral approach, trying to avoid the medial approach in traumatology. This article relates the differents surgical techniques. A preoperative computed tomography is needed to select the eligible fractures for those techniques. PMID- 17349387 TI - [Extra-articular elbow arthroscopy.] AB - Extra-articular elbow arthroscopy has to be considered as the evolution of the elbow surgery to a mini invasive endoscopically assisted surgery developed by the recent advance of the elbow arthroscopy. Various pathologies, such as lateral epicondylitis, ulnar nerve entrapment, distal Biceps tendon rupture, synovial cysts, or olecranon bursitis have been treated arthroscopically. Extra-articular pathologies can be treated through an intra-articular endoscopic approach. The true endoscopic extra-articular technique is proced through a real anatomical space or inside a space of work created de novo by the surgeon. The difficulty of using endoscopy in extra-articular pathologies of the elbow is related to the vasculo-nervous structures sourrounding the articulation wich are directly subject to potential injury. Elbow extra-articular endoscopy must be considered as a difficult and sometimes dangerous procedure reserved to experimented elbow arthroscopic surgeons. Those techniques are yet to demonstrate their superiority in term of results and security compare to the open techniques. PMID- 17349388 TI - [Set-up, portals and normal exploration in wrist arthroscopy.] AB - Arthroscopy is an accepted technique for evaluation of intra-articular pathology and treatment of a variety of disorders even in the wrist joint. Dedicated miniaturized instrumentation is needed along with a specific traction system. The external distraction alone (dry technique) allows for complete joint exploration and several type of arthroscopic surgery, avoiding annoying leaking in the subcutaneous tissues, though further distension of the articular pouches can be achieved by saline infusion (fluid distension or wet technique). Knowledge of surface anatomic landmarks and careful surgical technique are required for proper portal placement and in order to avoid injury to the numerous noble structures crossing nearby. Description of radio- and medio-carpal portals is provided along with the different bony, condral, synovial and ligamentous structures that can be visualised or treated through each portal. Surgeon can choose the most suitable portal for scope or instruments, according to specific needs for diagnostic or therapeutic purposes. PMID- 17349389 TI - [Therapeutic interest of wrist arthroscopy about 1000 cases.] AB - Wrist arthroscopy is a relatively recent procedure because it was described in the 70's. During the first period of 80's it became an indisputable technique of diagnosis. Since the 90's many therapeutic procedure were described by several authors all over the world. This technique increase a lot the understanding of wrist pathologies and ameliorate significantly the results for patients. We report our experience about 1000 wrist arthroscopy between 1998 and 2005. The patients were always operated on outpatient basis under local regional anaesthesiology. The arm was laid on the table and the hand on in-line traction (5-7 kg). We used a 2.4 mm arthroscope, 30 degrees angled. The both joints, radiocarpal and midcarpal, were systematically explored. The small portals were not closed. In our experience, only 42 arthroscopies (4%) were without surgical procedure. We separated the indications in 7 chapters: 1) arthoscopic assistance for fractures treatment (distal radius and scaphoid: 7%; 2) TFCC tears (17%); 3) treatment of intrinsic ligaments tears (scapholunate and lunotriquetral: 21%); 4) ectomy (radial styloidectomy, wafer, carpal boss 13%); 5) resection of wrist ganglia (21%); 6) partial prosthesis (2,5%); 7) others techniques (arthrolysis, synovectomy 14,5%). PMID- 17349390 TI - [Arthroscopic treatment of distal radius fracture.] AB - The orthopaedic surgeons cannot predict the functional results after a distal intra articular radius fracture. The intra-articular incongruity of more than 1 mm is associated with the development of secondary osteoarthrosis. The wrist arthroscopy became an essential help for the reduction of these fractures. The hand is normally in an upright position with a traction of approximately 4-5 kg which facilitates the reduction of the extra-articular fracture component. It is possible to use a technique of horizontal traction. The arthroscopy allows the reduction and control of the fixing of the various fragments, but also the treatment associated lesions associated. One randomized study, which compared 34 arthroscopically treated fractures with 48 openly treated, concluded that the arthroscopy-treated group had better outcome, better reduction, better grip strength and better range of motion than the openly treated group. The treatment of intra articular distal radius fractures with arthroscopic assistance is thus the guaranteeing of the most anatomical reduction of articular surface. It allows the diagnosis and the treatment of the associated lesions, decreases the peripheral fibrous scars of soft tissues by avoiding initially extensive approaches and finally gives better functional results. PMID- 17349391 TI - [Percutaneous fixation of scaphoid fractures with arthroscopic assistance.] AB - We report the results of a series of 37 recent fractures of the scaphoid treated by percutaneous screwing under X-ray control with systematic realization of a wrist arthroscopy. In 22 cases the factures were undisplaced and we had 15 displaced fractures. In all the cases the wrist arthroscopy allows to check the quality of the reduction, the good positioning of the screws and the correct reduction of fragments. Union was obtained in all cases with an average of 62 days (range 45-80). The functional recovery of the operated wrists was good with an early return to work on average 21 days (between 0 days and 3 months). The systematic association of wrist arthroscopy to the percutaneous screwing secures the procedure which can be proposed to motived patients interested by a fast return to the active life. The quality and the stability of the reduction are controlled and avoid complications due to bad positioning of the material. The possibility of treating in the same time the associated intra carpal ligaments tears lesions is possible. PMID- 17349392 TI - [Arthroscopic management of recent or chronic lesions of Triangular Fibrocartilage Complex of the wrist.] AB - Lesions of the triangular fibrocartilage complex of the wrist (TFCC) have perfectly been dismembered by Andrew Palmer and have largely benefited from progress of arthroscopy of the wrist. One distinguishes thus traumatic lesions (class 1) individualized according to their localization, central (1-A), ulnar (1 B), radial (1-D) or distal (1-C). Central lesions are classically associated to a positive ulnar variance. The clinical symptomatology evokes a meniscal like syndrome of the wrist. In case of failure of the medical treatment, it will be necessary to propose a surgical procedure guided by histopathology of the triangular complex. Thus, ulnar peripheral richly vascularized lesions (1-B) could therefore potentially heal and will have to benefit by an attempt of surgical reattachment (arthroscopic technique of Whipple, Poehling or other techniques) or by an osteosynthesis in case of fracture on the basis on the ulnar styloid process. Central fibrocartilage lesions (1-A) or radial avulsions (1-D) are less vascularized and have therefore little probability to heal; they will benefit then ideally from the endoscopic debridement of unstable flaps of the central portion of TFCC. No immobilization is required and rehabilitation is immediately undertaken. Less frequent class 1-C lesions justify in our practice a simple arthroscopic regularization, alone complete ruptures could have necessitate a direct suture. Class 2 degenerative lesions are graduated (A to E) according to evolution of the chondromalacia of the ulnar head and carpal bone, perforation of the central disc and lunotriquetral ligament degeneration. They are usually associated with a constitutional or an acquired ulnar plus variance syndrome, for example after a distal radius fracture malunion. The clinical symptomatology needs to differentiate them from the simple frequent physiological perforations after the age of 50 years. Arthroscopy will allow to regularize unstable non-vascularized lesions and to perform a wafer procedure through the large hole of the central disc. Alone lesions with very positive ulnar variance or fail of minimally invasive procedures, justify, in our experience, a shortening osteotomy of the ulna. PMID- 17349394 TI - [Arthroscopic styloidectomy.] AB - The radial styloidectomy is a symptomatic treatment of the radio scaphoidal impingement. Famous many years ago for the treatment of post-traumatic arthritis of the wrist (SLAC, SNAC wrist) this procedure has been progressively abandoned. The miniaturization of the wrist's arthroscopical tools allows stiloidectomy under arthroscopy. This treatment allows the disappearance of the impingement and protects the surrounding soft tissue. After a short historical, anatomical and biomechanical study, the authors expose the technique of the styloidectomy under an arthroscopic procedure. PMID- 17349393 TI - [Arthroscopic management of scapholunate instability.] AB - Scapholunate ligament tears cause chronic instability leading to SLAC. Wrist arthroscopy allows to see the lesions, even at an early stage, and to treat them with a simple K-Wires fixation in acute cases. Patients were treated on an outpatient basis with tourniquet and under regional anaesthesia. In acute cases, the scapholunate dissociation was reduced by external and internal manoeuvres. The fixation was done with pins under arthroscopic and fluoroscopic control. In chronic lesions, after wrist arthroscopy check, an electrothermal shrinkage can be performed in some cases. An arthroscopic classification was created with 4 grades. Wrist arthroscopy is the best technique for early diagnosis, and assures the best functional results. PMID- 17349395 TI - [Arthroscopic distal ulna resection after post traumatic ulno carpal abutment.] AB - Ulno carpal abutments secondary to the sequels of a fracture of the radius are often due to the inversion of the distal radio ulnar index by shortening relative to the radius. This positive ulnar variance eventually leads to an abutment between the head of the ulnar and the proximal articular face of the lunate with alteration of the cartilaginous carpal surfaces. The wrist arthroscopy makes diagnosis and treatment possible in a less invasive way. The patients are operated on as outpatients under local regional anaesthetic using a pneumatic tourniquet. The arthroscope is positioned using the 3-4 radio carpal opening permitting exploration of the joint. The surgical treatment is performed by arthroscopy using a burr and going in through the 6R radio carpal opening. In this way we use the technique of partial resection of the distal ulna. We have a series of 62 patients who have benefited from the technique of partial resection of the ulnar head by arthroscopy. There were 30 men and 32 women. The average age was 66 years old (between 45 and 82). Our average follow-up is 32 months (between 12 and 60 months). Recovery of mobility was immediate in all cases with persistent pain in the radio ulnar joint in 8 cases. Arthroscopic treatment of ulno carpal abutment has proved itself effective and innocuous. It should nevertheless be reserved for operations on small sized inversions of the distal radio ulnar index (less than 5 mm). In the event of larger ulnar variances we prefer ulnar shortening osteotomy. The other techniques will be restricted to cases where the distal radio ulnar joint has been impaired. PMID- 17349396 TI - [Arthroscopic treatment of the ulnar impaction syndrome.] AB - The ulnar impaction syndrome is due to hyperpressure in the ulnocarpal joint. It occurs most frequently following distal radial fractures with shortening, but can also be secondary to a primitive length discrepancy between a short radius and a long ulna (positive ulnar variance). Symptoms and clinical findings, even though characteristic, are not specific. Standard X rays show a positive ulnar variance, and sometimes a hyperpressure cyst in the lunate. CT arthroscan and MRI studies demonstrate indirect signs of hyperpressure. If medical treatment fails to improve the condition, the choice surgical technique is arthroscopic, allowing debridement of the TFCC central tear, and shortening of the horizontal aspect of the ulnar head. PMID- 17349397 TI - [Arthroscopic treatment of dorsal wrist ganglia.] AB - Incidentally discovered in 1987, arthroscopic treatment of dorsal wrist ganglia is based on our knowledge of their physiopathology which in turn benefits from the arthroscopic wrist evaluation. Dorsal wrist ganglia arise in the radiocarpal space from the dorsal part of the scapholunate ligament and migrate along the dorsal wrist capsule. According to their position above or under the dorsal intercarpal ligament, their cutaneous projection may vary. The basis of the arthroscopic treatment of wrist ganglia is, as with open surgery, the capsular resection in front of their origin. Arthroscopic resection is made either from dorsal radio-carpal or midcarpal approaches with little morbidity. Scars are unnoticeable, wrist mobility and strength close to normal by three months, which is the delay for dorsal wrist pain, always very limited, to disappear. The recurrence rate is however still debatable. Close to zero in some series, we had almost 20% recurrence rate in our series, with half of patients who reccur after two years follow-up. This variability in the recurrence rate also exists with open techniques. The only prospective and randomized study available to date found no differences between the two techniques, according to the recurrence rate. PMID- 17349398 TI - [Arthroscopic subacromial decompression.] AB - In 1983, Ellman reported the first subacromial decompression by arthroscopy as an alternative to open acromioplasty which described by Neer in 1972. Subacromial decompression combinates a removing of the antero lateral part of the acromion, a release of the coraco acromial ligament and a subacromial bursectomy. The principal indication is a chronic anterior impingement after failure to medical treatment. This subacromial decompression can be associated to cuff debridement, cuff repair, tenotomy or tenodesis of the biceps tendon or repair intraarticular lesion (SLAP, labrum...). The contraindications are massive cuffs tear with a superior migration of the humeral head or if the acromion is flat. Then, acromioplasty and release of the CA ligament could create a superior and anterior migration of the humeral head responsable to a pseudo paralytic shoulder. If we compare to open acromioplasty, arthroscopic decompression has some advantages; no split deltoid or desinsertion of anterior deltoid fibers, small cicatrices, less postoperative pain allowing immediate physiotherapy and possibility to explorate and to repair intra articular lesion during the same operation. PMID- 17349399 TI - [Arthroscopic Volar Wrist Ganglionectomy.] AB - As an original technique developed by our department, the preliminary result of arthroscopic resection of volar wrist ganglion was first published in 2003. Since then, there were few reports in the literature concerning this new treatment method. The aim of the study is to evaluate the long-term outcome of this treatment technique. From August 1997 to April 2005, 21 volar wrist ganglia with average size of 2 cm (range 1-4 cm) were treated. The average age of patients was 48.6 (range 18-63). Thirteen ganglia had previous treatment including either aspiration or open excision. Seventy-one percent of the operations were performed under local anesthesia. Wrist arthrogram was performed in 9 cases. Seven cases showed origin from radiocarpal joint and all proceeded to arthroscopic resection successfully. Arthroscopically, 75% of ganglia arose from the interval between radioscaphocapitate and long radiolunate ligament, and 25% from the interval between long radiolunate and short radiolunate ligament. Sixteen of the 21 ganglia could be excised by arthroscopic technique. The average follow up was 56 months (range 101 - 9 months). There were 2 recurrences. One was treated with repeated arthroscopic excision and the other by open excision. There was no impairment of wrist motion and function in all patients. No neurovascular complication was encountered. Arthroscopic resection was an effective treatment method for well-selected volar wrist ganglion arising from the radiocarpal joint in long run. PMID- 17349400 TI - [Arthroscopic management of articular cartilage defect.] AB - The chondral changes of the carpus are frequent, often after trauma but also being able to be secondary with degenerative disease. The wrist arthroscopy generally makes it possible to make the diagnosis of these lesions, before they are visible by the usual paraclinic examinations. It will make it possible to withdraw foreign body, cartilage or osseous fragments free in the articulation at the origin of pains. It will also allow the abrasion of small size area of chondral change. Lastly, it will be an essential tool for a secondary conventional treatment. The installation of partial implants in necrosis of proximal pole by arthroscopy is a recent technique very well adapted. PMID- 17349401 TI - [Arthroscopic wrist arthrolysis.] AB - Wrist stiffness is a complication of wrist trauma or surgery. Rehabilitation is the treatment of choice to improve the wrist range of motion. Since 1988 we used the arthroscopic wrist arthrolysis. Criteria for patient inclusion in our preop and postop study were wrist stiffness with or without pain, unsuccessful results from rehabilitation after 3 to 6 months. From 1988 to 2003, 47 cases (45 patients: 35 males and 10 females), with a mean age of 36 years were operated on. All the radiocarpal, midcarpal and DRUJ portals were used in relationship with the site of rigidity. At a mean follow up of 58 months (range from 3 to 176 months) no complications were documented. Pain was almost absent in all the cases, mean flexion-extension ROM increased from 92 degrees preop to 106 degrees postop, mean pronation/supination increased from 145 degrees preop to 155 degrees postop, and mean grip strength increased from 25 to 31 kg postop. The average modified Mayo Wrist Score improved from 39 to 87, and the postop DASH Questionnaire obtained an average of 21 points. PMID- 17349402 TI - [Arthroscopic treatment of osteoarthritis of scaphotrapezotrapezoid joint.] AB - Osteoarthritis of scaphotrapezotrapezoid joint corresponds to 13% of wrist arthritis. It is seldom isolated. The arthroscopic treatment associates a radial mid carpal portal and a STT portal called 1-2 midcarpal portal. Between 2002 and 2005, we carried out 13 resection isolated from the distal pole of the scaphoid. There were only women whose average age was 58 years. The improvement was real on the level of the pain, mobility and the muscular force. In same time, we operated on 13 patients by associating an implant in pyrocarbone as interposition after resection. The average age was 67 years. The average follow-up was 20 months. We had two implant dislocations for technical errors. The quality of the results helped by the invasive initially mini-approach and the arthroscopy can make it possible to select some indications. PMID- 17349403 TI - [Arthroscopy of the Trapeziometacarpal and Metacarpophalangeal Joints.] AB - Indications for small joint arthroscopy in the hand remain poorly understood. This is due to a paucity of papers discussing this technique in the literature, as well as inadequate hands on training in the pearls and pitfalls regarding this application within the commonly used "scope" of arthroscopy. Despite the fact that small joint arthroscopes have been available for over a decade, hand surgeons have been slow to adopt this technique within their treatment armamentarium for the treatment of both traumatic and degenerative conditions involving the thumb and the digital metacarpophalangeal joints. A proposed arthroscopic classification for basal joint osteoarthritis provides additional clinical information and can direct further treatment depending on the stage of disease. This chapter will also review the brief history of trapeziometacarpal arthroscopy and provide insight as to how this technique can be incorporated into a treatment algorithm in managing this common affliction. Metacarpophalangeal joint arthroscopy is even less commonly used, while traumatic and overuse injuries are frequently seen in the thumb, and present an ideal indication in certain scenarios. Painful conditions affecting the metacarpophalangeal joints of the fingers are less commonly seen, yet the small joint arthroscope presents a much clearer picture of the present pathology compared to other imaging techniques or even open, and potentially deleterious, surgery. The application of this technology to the smaller joints will soon make the treating surgeon realize that a myriad of pathologies are readily visible and can augment treatment, as well as diagnosis. Similar to the wrist, small joint arthroscopy may one day supplant imaging techniques such as MRI or CT in establishing an accurate diagnosis. PMID- 17349404 TI - [Arthroscopic surgery of the trapeziometacarpal joint.] AB - Treatments of 1st CMC joint arthritis are numerous. Arthroscopic surgery allows distal trapezium resection in early stage of CMC arthritis, avoiding more extensive classical open surgery. The distal trapezium resection is performed under arthroscopic control, associated to tendinous interposition. Between 2000 and 2005 we treated 32 patients. There were 26 women and 6 men. The average age was 56 years old (range 48-78). In 4 cases we had to transform the procedure in open surgery with trapezectomy. Postoperative pain were usual and long. We had technical fault with foreign bodies in one case, insufficient resection in 2 cases. One case presented a secondary joint collapses with necessity of other operation. PMID- 17349405 TI - [Complication and prevention of upper limb joints arthroscopy.] AB - Arthroscopy for upper limb joints disorders has been used increasingly over the past two decades, and is often considered by population as minor surgery. It would be a mistake to mask potential complications, even if they are less important than equivalent conventional technique. Complications depend on the joint, and despite the relative lack of experience for wrist and small joints, elbow arthroscopy seems to be the arthroscopic technique with most important complication rate. However, most of these complications remain minor and curable. Teaching of anatomy and arthroscopic techniques, respect of elementary prudence rules, should allow to control the risk and the learnig curve. Clear and honest information about potential complications provided to patient is certainly the best way to reduce consequences of these complications. PMID- 17349406 TI - [Arthroscopic treatment of calcifying tendinitis of the rotator cuff.] AB - The treatment of symptomatic calcifying tendinitis of the rotator cuff is usally medical. Whereas, chronic and painfull features can beneficiate of a surgical treatment. With shoulder arthroscopy it's possible to remove the type A and B calcifications and to perform a bursectomy and acromioplasty in type C uncollected. The clinical and radiological results with one year of follow-up upgrate 90% of good and excellent results. Calcifying tendinitis reatment appear like one of the best indications of the shoulder arthroscopy. PMID- 17349407 TI - [Contribution to the upper limb surgery.] PMID- 17349408 TI - [Arthroscopic surgery of the acromioclavicular joint.] AB - Lesion of the acromioclavicular joint is a usual clinical condition because of it superficial situation. It is often involved in trauma of the shoulder girdle. Moreover, degenerative changes are quite always observed for patients over 40. Distal clavicle resection as a treatment of acromioclavicular joint disease had been first described in 1941. Clinical results in term of mobility and shoulder pain are good and durable in time. Referring to the expansion arthroscopic techniques, distal clavicle resection lead to same middle and long term results as open surgery. Arthroscopic procedures have the theoretical advantages of no deltoid disruption and may help the surgeon to diagnose and treat associated lesions such as rotator cuff ruptures. More recently, arthroscopic surgeries for fresh and/or chronic acromioclavicular disjunctions were proposed. These procedures remain in development and need further evaluations. PMID- 17349409 TI - [Historical developments of upper limp arthroscopy.] AB - The fathers of arthroscopy are without any doubt Kenji Takagi and his disciple Masaki Watanabe. They initiated these procedures and allowed the developments at the origin of the hardware used at our time. Not without difficulty, professional societies were organized on the different continents and at the international level. The shoulder then the elbow, the wrist and the hand profited from considerable projections these last years to become techniques impossible to circumvent of the osteoarticular surgery. PMID- 17349410 TI - [Arthroscopic treatment of capsular shoulder stiffness.] AB - The shoulder capsular sitffness must be managed first by a physiotherapist and the arthroscopic release is indicated after failure. The clinical assessment is essential and reveals the loss of passive motion in specified direction. The x rays and imaging are necessary for excluding the other etiologies of shoulder stiffness. The arthroscopic treatment is part of he treatment strategy which has to be explained to the patient. The arthroscopic treatment starts by measuring under anesthesia the loss of passive motion. The next step consists of the release of the rotator interval followed by resection of the anterior capsule. Finally, the posterior capsule is cut according to the location of the capsular retraction. The interest of the subacromial debridement is still of debate. The postoperative pain control and the rehabilitation are part of the treatment. The literature analysis demonstrates the efficiency of the arthroscopic treatment, even if the post-op care are often long. A delay of 6 months is currently necessary to obtain the final results. The main advantages of the arthroscopic treatment is to address specifically the retracted capsule and to perform a selective release which allow to start rehabilitation program early. PMID- 17349411 TI - [Shoulder arthroscopy. Partial thickness tears of the rotator cuff.] AB - Partial tears are frequent in rotator cuff pathology. Articular-side lesions, bursal-side lesion and interstitial lesion inside the thickness of the tendon are described. Etiopathogeny is not clearly known. It seems a multifactory association with intrinsic tendinous factors (vascularity, normal ageing of the tendon), extrinsic mechanical factors (impingement syndrome) and trauma. Clinically, the complaint is a painful shoulder with full range of motion. The rotator cuff examination does not shown weakness but pain. The onset is traumatic or degenerative. It could be the consequence of overuse specially in case of overhead sport. Diagnosis is confirmed by arthro-CT or/and (arthro) MRI. It is useful for the treatment to determine the size of the rupture regarding the thickness of the tendon. Natural history shows that partial tears do not healed. Treatment of the partial tear of the cuff is still debatable particularly for intertstitial lesion (acromioplasty, debridment, repair). Isolated acromioplasty permit to obtain pain relief but do not prevent evolution to full-thickness tear when the lesion concern more than 50% of the thickness of the tendon. In this case, arthroscopic tendon repair gives good and reliable results. PMID- 17349412 TI - [Arthroscopic repair of full-thickness tears of the rotator cuff.] AB - INTRODUCTION: Shoulder arthroscopy was only at first a surgical technique for subacromial decompression and has been progressively extended to the cuff repairs. This surgery remains nevertheless difficult and requires to be described exactly. A multicenter study of the French Arthroscopic Society allowed to analyse and to underline the quality of the clinical and anatomical results. SURGICAL TECHNIQUE: The technique is described exactly as well as the necessary material. Repair will be adapted to the size and the location of the tear. The technical skill should be simple, effective and reproducible to obtain the best anatomical result. RESULTS: The Constant score improved from an average 46.3 (13.4) to 82.7 (+/-10.3) at the last follow-up, with 62% of patients' symptom free. Strength improved from 5.8 (+/-3.7) to 13.6 (+/-5.4). Ninety-four percent of the results were rated as excellent or good (Constant score>65). A watertight repair was found in 74.1% of the cases. DISCUSSION: Numerous correlations allow to confirm the results found in the literature: the healing of the cuff improves global functional results even when the tear is massive; anatomical result depends on the size of the initial tear; preoperative fatty degeneration is an important predictive factor; the healing of the cuff is related to the age. The quality of the results, the evolution of the material, the simplification and the codification of the surgical technique make it an accessible, effective reproducible surgery. PMID- 17349413 TI - [SLAP lesions: treatment.] AB - The advent of shoulder arthroscopy, as well as our improved understanding of shoulder anatomy and biomechanics, has led to the identification of previously undiagnosed lesions involving the superior labrum and biceps tendon anchor. Although the history and physical examinations as well as improved imaging modalities (arthro-MRI, arthro-CT) are extremely important in understanding the pathology, the definitive diagnosis of superior labrum anterior to posterior (SLAP) lesions is accomplished through diagnostic arthroscopy. Treatment of these lesions is directed according to the type of SLAP lesion. Generally, type I did not need any treatment, type III are debrided, whereas type II and many type IV lesions are repaired. The purpose of this article is to review the anatomy, classification, diagnosis and current treatment recommendations of SLAP lesions. PMID- 17349414 TI - [Arthroscopic treatment of shoulder fractures.] AB - Therapeutic options for shoulder joint fractures include conservative treatment or surgery, but indications for either treatment remain vague. Arthroscopic treatment of glenoid fractures and greater tuberosity fractures represents an alternative and allows anatomical reduction and reliable fixation with decreased soft tissue trauma. With this minimally invasive technique, large muscular dissections are avoided and postoperative recovery is shortened. This technique also allows a complete joint inspection and a more accurate diagnosis for associated injuries than conventional imaging methods. Arthroscopy is a useful diagnostic tool that may avoid underestimation of these associated injuries (labrum, rotator cuff tendons, cartilage) and is also helpful for treating these lesions in the same time. However, arthroscopic treatment of shoulder fractures needs a learning curve depending on surgeon's experience in shoulder arthroscopy. At present, indications for arthroscopic treatment of shoulder fractures are limited to anterior or posterior glenoid rim fractures and some greater tuberosity fractures. This selection is best made using preoperative computed tomography and especially 2D reconstruction. PMID- 17349415 TI - [Shoulder arthroscopy: setting, portals and normal exploration.] AB - Arthroscopy has been established as a valuable technique in diagnosis and treatment of the injured and deseased shoulder. Arthroscopy is not a new diagnostic tool but offers new approaches to the surgical treatment of shoulder pathology. Shoulder arthroscopy is usally performed under general anesthesia or/with scalene block. The patient is positioned in opposite lateral decubitus position or in beach chair position. Diagnostic arthroscopic is initiated with insertion of the arthroscope from the posterior portal into the gleno humeral joint. Inspection should be organized systematic visualization of the entire joint (articular surfaces of the glenoid and humeral head, glenoid labrum, long head of the biceps tendon, sub scapularis tendon, axillary pouch, capsular ligaments, synovial membrane). Then endoscopic visualization of the subacromail space is a valuable and essential adjunct to the gleno humeral arthroscopy (impingement syndrome, rotator cuff tears, calcific tendinitis, acromio calvicular joint disorders). PMID- 17349416 TI - [Arthroscopic treatment of anterior glenohumeral instability.] AB - Arthroscopic treatment of anterior shoulder instability is now well defined but its learning curve remains long. This technique should only be used for a certain kind of instability. Surgical gesture should be acquired such as the different devices that are proposed. Arthroscopic techniques are still in progress and results are improving with the selection of patient who could benefit by it. PMID- 17349417 TI - [Endoscopic treatment of snapping scapula.] AB - We describe an endoscopic method for resection of the superomedial corner of the scapula in cases of painful snapping scapula. A preoperative computed tomography may be useful to show narrowing between the superomedial corner and the chest wall. Endoscopic technique gives the same goods results than open surgery with in cosmetic advantage and early rehabilitation. Avoided neurological lesion need to perform a precise portal placement. PMID- 17349419 TI - Risedronate-induced Hepatitis. PMID- 17349421 TI - Orthostatic intolerance in chronic fatigue syndrome. PMID- 17349422 TI - Asian Indians and coronary artery disease risk. PMID- 17349423 TI - Obstructive sleep apnea in minorities. PMID- 17349425 TI - Outcomes and physician specialty among patients with heart failure: association is not causation. PMID- 17349427 TI - Reduce the risk of reinfarction and related complications after myocardial infarction. PMID- 17349429 TI - Progression of chronic kidney disease: can it be prevented or arrested? PMID- 17349430 TI - ADAPT trial data. PMID- 17349434 TI - Treatment of Staphylococcus aureus prosthetic valve endocarditis. PMID- 17349436 TI - The trialist, meta-analyst, and journal editor: lessons from ADAPT. PMID- 17349437 TI - Hepatocellular cancer: a guide for the internist. AB - Hepatocellular cancer is the third leading cause of cancer-related deaths worldwide. Its incidence has increased dramatically in the United States because of the spread of hepatitis C virus infection and is expected to increase for the next 2 decades. Hepatitis B virus, hepatitis C virus, and chronic heavy alcohol use leading to cirrhosis of the liver remain the most important causes. The diagnosis of hepatocellular cancer rests on a combination of radiologic, serologic, and histopathologic criteria. Liver transplantation is the only definitive treatment. Resection of the tumor and other percutaneous therapies are more commonly used in practice, because most hepatocellular cancers are detected at an advanced stage. Patients who are at high risk for the development of hepatocellular cancer should be screened with an ultrasound of the liver every 6 months. The prognosis is dependent on both the underlying liver function and the stage at which the tumor is diagnosed. The aim of this review is to familiarize internists in screening, diagnosis, and referral of patients with hepatocellular cancer in an appropriate and timely fashion. PMID- 17349438 TI - Meta-analysis comparing CT colonography, air contrast barium enema, and colonoscopy. AB - INTRODUCTION: Published studies have reported a wide range of sensitivities and specificities for computed tomographic (CT) colonography for polyp detection, generating controversy regarding its diagnostic accuracy. METHODS: A meta analysis of published studies comparing the accuracies of CT colonography and colonoscopy for polyp detection was performed. The pooled per-patient sensitivities and specificities were calculated at various thresholds for polyp size. Summary receiver operating characteristic (sROC) curves were also constructed. RESULTS: Thirty studies were included in the meta-analysis of CT colonography. The pooled per-patient sensitivity of CT colonography was higher for polyps greater than 10 mm (0.82, 95% confidence interval [CI], 0.76-0.88) compared with polyps 6 to 10 mm (0.63, 95% CI, 0.52-0.75) and polyps 0 to 5 mm (0.56, 95% CI, 0.42-0.70). Similarly, the exact area under the sROC curve (area +/- standard error) was higher using a threshold greater than 10 mm (0.898 +/- 0.063) compared with thresholds of greater than 5 mm and any size (0.884 +/- 0.033 and 0.822 +/- 0.059, respectively). There were no significant differences in the diagnostic characteristics of 2-dimensional versus 3-dimensional CT colonography. At a threshold greater than 5 mm, the exact area under the sROC curve was significantly higher for endoscopic colonoscopy compared with CT colonography (0.998 +/- 0.006 vs 0.884 +/- 0.033, P < .005). CONCLUSIONS: CT colonography has a reasonable sensitivity and specificity for detecting large polyps but was less accurate than endoscopic colonoscopy for smaller polyps. Thus, CT colonography may not be a reasonable alternative in situations in which a small polyp may be clinically relevant. PMID- 17349439 TI - Office management of geriatric urinary incontinence. AB - Urinary incontinence is a common and potentially disabling condition affecting 15% to 30% of those aged 65 years and older. It adversely affects physical health, psychological well-being, and health care costs. Even when it is not curable, proper management of urinary incontinence can lead to improved quality of life for patients and caregivers. Despite its prevalence, many geriatric patients suffering from urinary incontinence are undiagnosed and untreated. Patients often do not report the problem, and health care professionals often do not ask about it. Health care professionals should therefore learn to identify, evaluate, and manage urinary incontinence based upon the available evidence and practice guidelines. Although the evidence base for specific recommendations for the office evaluation and management of geriatric urinary incontinence is limited, a basic evaluation to identify treatable causes of incontinence, referral of appropriate patients for further evaluation, and several noninvasive management strategies can greatly improve these symptoms in many older patients. PMID- 17349440 TI - Updates in the management of gout. AB - The majority of patients with gout are cared for by primary care physicians. Although both the physician and patient may easily recognize the acute arthritis of gout, errors in selecting the most appropriate medication and proper dose are common. The clinical stages of gout include asymptomatic hyperuricemia, intermittent gouty arthritis, and chronic tophaceous gout. Treatment of gout is usually considered after the first attack of arthritis, typically podagra. The aims of treatment are to alleviate the pain and inflammation associated with acute attacks, prevent future attacks, and decrease uric acid levels. Confusion frequently arises because certain medications such as colchicine may have dual purposes: to treat an acute attack and to suppress future attacks. The purpose of this management update is to provide practical advice about prescribing the proper medication considering both treatment goals and patient comorbidities. PMID- 17349441 TI - A cautionary tale. PMID- 17349442 TI - An absorbing problem. PMID- 17349443 TI - Pressured to appear. PMID- 17349444 TI - It's elemental. PMID- 17349445 TI - Looks like snow. PMID- 17349446 TI - The impersonator. PMID- 17349447 TI - Increasing trends in incidence of overweight and obesity over 5 decades. AB - PURPOSE: We evaluated trends in the incidence of overweight and obesity over the past 50 years. METHODS: We evaluated trends in the incidence of overweight (25< or =body mass index [BMI] <30 kg/m2), obesity (BMI > or =30 kg/m2) and stage 2 obesity (BMI > or =35 kg/m2) from 1950 to 2000 in Framingham Study participants (n=6798, 54% women). Individuals aged 40-55 years who attended 2 examinations 8 years apart in each decade were eligible. RESULTS: The incidences of overweight, obesity, and stage 2 obesity increased across the decades in both sexes (P for trend <.001). For men, the incidence of overweight rose from 21.8% (95% confidence interval [CI], 17.6-26.5) in the 1950s to 35.2% (95% CI, 28.6-42.5) in the 1990s; of obesity from 5.8% (95% CI, 4.4-7.6) to 14.8% (95% CI, 12.2-17.9); and of stage 2 obesity from 0.2% (95% CI, 0.1-0.9) to 5.4% (95% CI, 4.0-7.2). For women, incidence rates of overweight increased from 15.0% (95% CI, 12.3-18.1) to 33.1% (95% CI, 29.0-37.4); of obesity from 3.9% (95% CI, 2.9-5.3) to 14% (95% CI, 11.6-16.7); and of stage 2 obesity from 1.7% (95% CI, 1.1-2.6) to 4.4% (95% CI, 3.2-6.0). Overall, incidence rates of overweight increased 2-fold and that of obesity more than 3-fold over 5 decades, findings that remained robust upon additional adjustment for baseline BMI in each decade. CONCLUSIONS: The incidence of overweight and obesity increased progressively over the last 5 decades, suggesting that the rising trend in prevalence is not a recent phenomenon. PMID- 17349448 TI - Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. AB - PURPOSE: Cyclical patterns of compliance have been observed with many health related activities such as dieting and exercise. It is not known whether such patterns of compliance exist among users of chronic medications. We sought to estimate the percentage of patients who restart osteoporosis therapy after a prolonged lapse in medication use and to identify the factors associated with a return to compliance. METHODS: We studied 26,636 new users of an osteoporosis medication (alendronate, calcitonin, estrogen, raloxifene, or risedronate) who were age 65 or older and had an extended lapse in refill compliance, defined as a period of at least 60 days after the completion of one prescription in which no refill for any osteoporosis medication was obtained. Survival curves were used to estimate the length of time until therapy is resumed. We estimated the association between patient characteristics and the rate of resuming treatment using Cox proportional hazards analysis. We then conducted a case crossover analysis to examine whether certain events occurring during follow-up triggered a return to refill compliance. RESULTS: Of patients who stopped therapy for at least 60 days, an estimated 30% restarted treatment within 6 months, and 50% restarted within 2 years. Among patients who had at least 6 months of continuous use before their interruption in treatment (n=5863), 42% restarted therapy within 6 months and 59% within 2 years. Younger patients, women, and those with a history of a fracture were more likely to return after a break in medication use. Recent hip fractures, discharges from nursing homes, and bone mineral density testing also predicted a return to treatment. CONCLUSION: Extended gaps in treatment are common among users of osteoporosis medications. Because the effectiveness of these drugs used in an interrupted way is unknown, compliance interventions should emphasize the need for continuous medication use. Further research is needed to understand why patients often go for months without refilling prescriptions and also whether similar utilization patterns exist for other chronic medications. PMID- 17349449 TI - Development of a risk score for colorectal cancer in men. AB - BACKGROUND: Colorectal cancer is a common and preventable disease for which screening rates remain unacceptably low. METHODS: We developed a risk scoring system for the development of colorectal cancer among participants in the Physician's Health Study, a prospective cohort of 21,581 US male physicians who were all free of cancer. Predictors of colorectal cancer were self-reported and identified from the baseline questionnaire. Logistic regression was used to determine the independent predictors of incident colorectal cancer over the follow-up period. Risk scores were created from the sum of the odds ratios of the final predictors and used to divide the cohort into categories of increasing relative risk. RESULTS: During 20 years of follow-up, 381 cases of colon cancer and 104 cases of rectal cancer developed in the cohort. Age, alcohol use, smoking status, and body mass index were independent significant predictors of colorectal cancer. The point scores were used to define 10 risk groups. Those in the highest risk group (9-10 points) had an odds ratio of 15.29 (6.19-37.81) for colorectal cancer compared with those with the lowest risk. We further stratified scores into 3 risk classes. Compared with those at the lowest relative risk, the odds ratio for colorectal cancer was 3.07 (2.46-3.83) in the intermediate risk group and 5.75 (4.44-7.44) in the highest risk group. CONCLUSIONS: We developed a simple scoring system for colorectal cancer that identifies men at increased relative risk on the basis of age and modifiable factors. This tool should be validated in other populations. PMID- 17349450 TI - Smoking, alcohol consumption, and Raynaud's phenomenon in middle age. AB - BACKGROUND: Data suggest Raynaud's phenomenon shares risk factors with cardiovascular disease. Studies of smoking, alcohol consumption, and Raynaud's have produced conflicting results and were limited by small sample size and failure to adjust for confounders. Our objective was to determine whether smoking and alcohol are independently associated with Raynaud's in a large, community based cohort. METHODS: By using a validated survey to classify Raynaud's in the Framingham Heart Study Offspring Cohort, we performed sex-specific analyses of Raynaud's status by smoking and alcohol consumption in 1840 women and 1602 men. Multivariable logistic regression analyses were used to examine the relationship of Raynaud's to smoking and alcohol consumption. RESULTS: Current smoking was not associated with Raynaud's in women but was associated with increased risk in men (adjusted odds ratio [OR] 2.59, 95% confidence interval [CI], 1.11-6.04). Heavy alcohol consumption in women was associated with increased risk of Raynaud's (adjusted OR 1.69, 95% CI, 1.02-2.82), whereas moderate alcohol consumption in men was associated with reduced risk (adjusted OR 0.51, 95% CI, 0.29-0.89). In both genders, red wine consumption was associated with a reduced risk of Raynaud's (adjusted OR 0.59, 95% CI, 0.36-0.96 in women and adjusted OR 0.30, 95% CI, 0.15-0.62 in men). CONCLUSIONS: Our data suggest that middle-aged women and men may have distinct physiologic mechanisms underlying their Raynaud's, and thus sex-specific therapeutic approaches may be appropriate. Our data also support the possibility that moderate red wine consumption may protect against Raynaud's. PMID- 17349451 TI - Cost-effectiveness of treatment for hepatitis C in an urban cohort co-infected with HIV. AB - PURPOSE: Recent clinical trials have evaluated treatment strategies for chronic infection with hepatitis C virus (HCV) in patients co-infected with human immunodeficiency virus (HIV). Our objective was to use these data to examine the cost-effectiveness of treating HCV in an urban cohort of co-infected patients. METHODS: A computer-based model, together with available published data, was used to estimate lifetime costs (2004 US dollars), life expectancy, and incremental cost per year of life saved (YLS) associated with 3 treatment strategies: (1) interferon-alfa and ribavirin; (2) pegylated interferon-alfa; and (3) pegylated interferon-alfa and ribavirin. The target population included treatment-eligible patients, based on an actual urban cohort of HIV-HCV co-infected subjects, with a mean age of 44 years, of whom 66% had genotype 1 HCV, 16% had cirrhosis, and 98% had CD4 cell counts >200 cells/mm3. RESULTS: Pegylated interferon-alfa and ribavirin was consistently more effective and cost-effective than other treatment strategies, particularly in patients with non-genotype 1 HCV. For patients with CD4 counts between 200 and 500 cells/mm3, survival benefits ranged from 5 to 11 months, and incremental cost-effectiveness ratios were consistently less than $75,000 per YLS for men and women of both genotypes. Due to better treatment efficacy in non-genotype 1 HCV patients, this group experienced greater life expectancy gains and lower incremental cost-effectiveness ratios. CONCLUSIONS: Combination therapy with pegylated interferon-alfa and ribavirin for HCV in eligible co-infected patients with stable HIV disease provides substantial life expectancy benefits and appears to be cost-effective. Overcoming barriers to HCV treatment eligibility among urban co-infected patients remains a critical priority. PMID- 17349452 TI - NSAID use and progression of chronic kidney disease. AB - PURPOSE: The effects of nonselective and selective cyclooxygenase-2 specific (COX 2) nonsteroidal anti-inflammatory drug (NSAID) use on the progression of chronic kidney disease (CKD) is uncertain. Due to the high prevalence of both CKD and NSAID use in older adults, we sought to determine the association between NSAID use and the progression of CKD in an elderly community-based cohort. METHODS: All subjects > or =66 years of age who had at least one serum creatinine measurement in 2 time periods (July-December, 2001 and July-December, 2003) were included. Multiple logistic regression analyses, including covariates for age, sex, baseline estimated glomerular filtration rate (eGFR), diabetes, and comorbidity were used to explore the associations of NSAID use on the primary (decrease in eGFR of > or =15 mL/min/1.73) and secondary (mean change in eGFR) outcomes. RESULTS: A total of 10,184 subjects (mean age 76 years; 57% female) were followed for a median of 2.75 years. High-dose NSAID users (upper decile of cumulative NSAID exposure) experienced a 26% increased risk for the primary outcome (odds ratio [OR] 1.26, 95% confidence interval [CI], 1.04-1.53). A linear association between cumulative NSAID dose and change in mean GFR also was seen. No risk differential was identified between selective and nonselective NSAID users. CONCLUSIONS: High cumulative NSAID exposure is associated with an increased risk for rapid CKD progression in the setting of a community-based elderly population. For older adult patients with CKD, these results suggest that nonselective NSAIDs and selective COX-2 inhibitors should be used cautiously and chronic exposure to any NSAID should be avoided. PMID- 17349453 TI - Assessment of FIBROSpect II to detect hepatic fibrosis in chronic hepatitis C patients. AB - BACKGROUND: The degree of liver fibrosis in patients with Hepatitis C (HCV) provides important prognostic information; however, the only current method available to obtain this information is by performing a liver biopsy. Liver biopsies are invasive, associated with complications, and costly. There has been recent interest in developing a panel of serum markers that can reliably predict the presence of fibrosis and, thus, obviate the need for a liver biopsy. Our objective was to prospectively validate a panel of serum fibrosis markers (FIBROSpect(SM) II) that has been recently developed. METHODS: Serum was obtained from 108 consecutive HCV (15% with HCV/ETOH) patients seen in a hepatology clinic at a single tertiary care center at the time of liver biopsy. The performance of FIBROSpect II (consisting of 3 fibrosis markers: hyaluronic acid, tissue inhibitor of metalloproteinases 1, and alpha-2-macroglobulin) in differentiating mild (F0-F1) from significant (F2-F4) fibrosis was assessed by comparing the panel results with performed liver biopsy. RESULTS: The prevalence of significant fibrosis in the study group was 36.1%. The diagnostic value of the serum marker panel to detect significant fibrosis as assessed by area under the receiver operating characteristic (ROC) curve was 0.826. Performance characteristics are as follows: sensitivity 71.8%, specificity 73.9%, positive predictive value 60.9%, negative predictive value 82.3%, and overall accuracy of 73.1%. CONCLUSION: This prospective study supports the clinical utility of serum markers in detecting fibrosis and validates the performance of FIBROSpect II in a prospective cohort of patients. The high negative predictive value of the test provides a reliable alternative to rule out severe fibrosis. PMID- 17349454 TI - Physician preferences and attitudes regarding industry support of CME programs. PMID- 17349456 TI - Updating electrocardiography standards. PMID- 17349458 TI - Short-term dynamics in fibrillatory wave characteristics at the onset of paroxysmal atrial fibrillation in humans. AB - INTRODUCTION: The purpose of this study was to investigate the magnitude and time course of fibrillatory wave dynamics during spontaneous onset of paroxysmal atrial fibrillation (AF). METHODS: We studied fibrillatory waves in Holter recordings of paroxysmal AF with regard to the fibrillation-free interval (FFI) preceding each episode. RESULTS: For 38 episodes of paroxysmal AF in 20 patients, dominant frequency (DF) ranged from 4.4 to 6.8 Hz (5.5 +/- 0.5 Hz). Long-FFI episodes showed a gradual increase in DF over the first 4 minutes (P < .0001). Short-FFI episodes showed an increase only from the first to the second minute (P < .003). For all 7 patients exhibiting both long-FFI and short-FFI episodes, short-FFI episodes had a higher initial DF (P < .002). CONCLUSION: The dynamics during onset and their relation to the FFI are consistent with the influence of short-term electrophysiological changes and their reversal. These findings have implications for the timing of antifibrillatory interventions. PMID- 17349459 TI - Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift. AB - Recent analysis of clinical data and a clearer understanding of the role of chemical structure in the development of cross-reactivity indicate that the increased risk of an allergic reaction to certain cephalosporins in penicillin allergic patients is smaller than previously postulated. Medline and EMBASE databases were searched using the following keywords: cephalosporin, penicillin, allergy, and cross-sensitivity for the years 1960 to 2005. Among 219 articles retrieved, 106 served as source material for this review. A significant increase in allergic reactions to cephalothin, cephaloridine, cephalexin, cefazolin, and cefamandole was observed in penicillin-allergic patients; no increase was observed with cefprozil, cefuroxime, ceftazidime, or ceftriaxone. Clinical challenges, skin testing, and monoclonal antibody studies point to the paramount importance of similarities in side chain structure to predict cross-allergy between cephalosporins and penicillins. First-generation cephalosporins have a modest cross-allergy with penicillins, but cross-allergy is negligible with 2nd- and 3rd-generation cephalosporins. Particular emphasis is placed on the role of chemical structure in determining the risk of cross-reactivity between specific agents. PMID- 17349460 TI - Oral beta-lactams in the treatment of acute otitis media. AB - Acute otitis media (AOM) is an important infectious disease among children throughout the world. The management of AOM is complicated by difficulties in diagnosis, spontaneous resolution, altered microbiology after pneumococcal conjugate vaccine use, and expanding antimicrobial resistance. The recent introduction of the heptavalent pneumococcal vaccine has resulted in a decrease in AOM due to penicillin-nonsusceptible strains of Streptococcus pneumoniae (PNSP) and an increase in infection due to beta-lactamase-positive nontypeable Haemophilus influenzae. The results of in vitro susceptibility testing in the context of broad surveillance programs provide useful information regarding the potency and spectrum of the oral beta-lactam antibacterial agents used in the treatment of AOM. The application of pharmacokinetic/pharmacodynamic breakpoints provides an effective means of projecting the potential clinical efficacy of the available agents. In view of what appears to be an increase prominence of beta lactamase-positive Gram-negative AOM pathogens and a decrease in PNSP, it appears that empiric therapy for AOM should now include an agent with activity against beta-lactamase-positive H. influenzae and S. pneumoniae. PMID- 17349461 TI - Role of oral extended-spectrum cephems in the treatment of acute exacerbation of chronic bronchitis. AB - Risk stratification is the recommended approach for treatment of acute exacerbation of chronic bronchitis (AECB) to optimize the chances of clinical success. The suggested oral therapy for "simple or uncomplicated" AECB, which is predominantly a result of infection due to Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, includes advanced macrolides and 2nd- or 3rd-generation cephalosporins, in addition to the older 1st-line agents (aminopenicillins, doxycycline, trimethoprim/sulfamethoxazole, and erythromycin). In light of increasing resistance of H. influenzae and S. pneumoniae to the older agents, the specific directed structural modification of the cephalosporin nucleus resulted in the development of extended-spectrum 3rd-generation oral cephems with enhanced beta-lactamase stability and improved activity against Gram positive pathogens (penicillin-susceptible S. pneumoniae and oxacillin susceptible Staphylococcus aureus). Analysis of results of double-blind randomized clinical trials assessing efficacy of the extended-spectrum oral cephems published since 2000 demonstrates that both cefdinir and cefditoren have similar point estimates of success in comparison to their comparators (cefuroxime, cefprozil, or Locarbacef), when either the clinical cure or the bacteriologic response was analyzed. Thus, oral extended-spectrum 3rd-generation cephems, which retain antimicrobial efficacy against the traditional respiratory pathogens despite changing resistance patterns, offer excellent coverage against the key pathogens involved in simple or uncomplicated AECB. PMID- 17349463 TI - A biomechanical comparison of the modified Mason-Allen stitch and massive cuff stitch in vitro. AB - PURPOSE: The suture-tendon interface is generally regarded as the weak link in rotator cuff fixation. High rates of failure in arthroscopic rotator cuff repair have led to a search for strong yet easy-to-perform suture configurations. The goal of this study was to compare the strength of 2 commonly used suture configurations, the modified Mason-Allen stitch and the massive cuff stitch, when suture-anchored into bone. METHODS: Fourteen sheep shoulders were harvested and the infraspinatus tendon isolated. Each infraspinatus tendon was split in half longitudinally along the axis of its fibers to yield 2 tendon-bone specimens per shoulder, for a total of 28 specimens. Each split tendon was then repaired by use of a double-loaded suture anchor with a modified Mason-Allen and simple suture in one specimen and the massive cuff stitch in the other. Each specimen was initially cyclically loaded on a vertical MTS uniaxial load frame (MTS Systems, Eden Prairie, MN) under force control from 5 to 30 N at 0.25 Hz for 20 cycles. Each specimen was then loaded to failure under displacement control at a rate of 1 mm/s. Peak-to-peak displacement, cyclic elongation, ultimate tensile load, stiffness, and mode of failure were recorded. A repeated-measures analysis of variance was performed, with an alpha level of significance set at P < .05. RESULTS: No statistically significant difference was found with regard to ultimate load to failure between the modified Mason-Allen stitch (110.4 +/- 55.1 N) and massive cuff stitch (116.4 +/- 37.9 N). In addition, no statistically significant difference was found with regard to cyclic elongation, peak-to-peak displacement, or initial displacement. The most common mode of failure for both suture configurations was suture pullout. CONCLUSIONS: The modified Mason-Allen stitch and massive cuff stitch yield similar biomechanical profiles when suture anchored into bone. CLINICAL RELEVANCE: The massive cuff stitch may be a simpler and biomechanically equivalent alternative to the modified Mason-Allen stitch in arthroscopic rotator cuff repair. PMID- 17349464 TI - The cam effect of the proximal humerus: its role in the production of relative capsular redundancy of the shoulder. AB - PURPOSE: The purpose of this study was to investigate quantitatively the cam effect of the proximal humerus (whereby the anteroinferior capsule of the shoulder is tensioned in abduction-external rotation by virtue of asymmetric rotation of the eccentrically positioned humeral head), as well the extent to which a reduction in the cam effect would cause a relative capsular redundancy, in the cadaveric shoulder. METHODS: Five fresh-frozen cadaveric shoulders were tested. K-wires were used to sequentially position the shoulder in 3 different positions: neutral anatomic position, with contact at the glenoid bare spot; 90 degrees-90 degrees neutral shift position, with contact at the glenoid bare spot; and 90 degrees-90 degrees posterosuperior shift position, with contact 4.3 mm posterosuperior to the glenoid bare spot. The topographic anterior band distance (TABD) was measured with the shoulder in each of the 3 positions. The relative redundancy that occurred by shifting the glenohumeral contact point was determined by subtracting the TABD in the 90 degrees-90 degrees posterosuperior shift position from the TABD in the 90 degrees-90 degrees neutral shift position. RESULTS: The results of repeated-measures analysis of variance showed significant differences among the mean TABD values for the 3 positions (P < .010). There was a significant increase in TABD when the shoulder was brought from the neutral anatomic position to the 90 degrees-90 degrees neutral shift position (P < .020), confirming the cam effect of the proximal humerus in the 90 degrees-90 degrees position. Furthermore, the TABD decreased significantly when the 90 degrees-90 degrees neutral shift position changed to the 90 degrees-90 degrees posterosuperior shift position (P < .005), indicating a significant reduction in the cam effect with a concomitant relative redundancy in the anteroinferior capsuloligamentous complex. CONCLUSIONS: The proximal humerus produces a significant cam effect on the anteroinferior capsule when the shoulder is brought into a position of 90 degrees abduction and 90 degrees external rotation. A reduction in the cam effect as a result of a posterosuperior shift of the glenohumeral contact point with the shoulder in the 90 degrees-90 degrees position results in a relative redundancy of the anteroinferior capsuloligamentous complex. This relative capsular redundancy, coupled with the pseudolaxity that occurs with SLAP lesions, can produce a degree of apparent anterior laxity that is independent of any true translational anterior instability. CLINICAL RELEVANCE: The relative redundancy in the anteroinferior shoulder capsule caused by a decrease in the cam effect of the proximal humerus may have clinical implications in the pathophysiology of the disabled throwing shoulder. This relative redundancy is a secondary pseudolaxity, with the primary pathology being a tight posteroinferior capsule. Appropriate treatment (stretching of the posteroinferior capsule) of the primary pathology is a more appropriate initial treatment than instability surgery. PMID- 17349465 TI - The superior-medial shoulder arthroscopy portal is safe. AB - PURPOSE: The superior-medial (SM) shoulder arthroscopic portal (Neviaser portal) is the portal anatomically closest to the suprascapular nerve, and any potential benefits of this portal would be mitigated if risk of suprascapular nerve injury were significant. The purpose of this study is to determine the safety of the SM arthroscopic shoulder portal. We hypothesize that the SM shoulder arthroscopic portal is safe. METHODS: Twelve fresh cadaveric shoulders were securely positioned to simulate shoulder arthroscopy in the beach-chair position with the arm at the patient's side in neutral rotation. An SM portal was established 1 cm medial to the acromion and 1 cm posterior to the clavicle, and a 5.5-mm burr sheath was oriented toward the acromioclavicular joint. The skin and trapezius were resected, the supraspinatus was retracted, and the suprascapular nerve was identified. The distance between the sheath and the nerve was measured by 2 independent observers with calipers. A safe distance was defined as 10 mm. RESULTS: The measured distances between the nerve and burr ranged from 18.5 to 35.7 mm, with a mean of 24.2 +/- 5 mm. The distance is significantly greater than the safe distance of 10 mm (P < .0001). CONCLUSIONS: This study shows that the SM portal is safe. The distance between an instrument oriented toward the acromioclavicular joint via the SM portal and the suprascapular nerve was 18.5 mm or greater in all specimens. CLINICAL RELEVANCE: Our study has clinical relevance because the SM portal is useful for arthroscopic rotator cuff repair, arthroscopic superior labrum repair, and arthroscopic distal clavicle excision. PMID- 17349466 TI - The subscapularis footprint: an anatomic description of its insertion site. AB - PURPOSE: The purpose of this study was to describe the anatomic footprint of the subscapularis tendon. METHODS: We examined 19 cadaveric shoulder specimens in this study. Dissection was carried out to the level of the subscapularis through a deltopectoral approach. The subscapularis tendon was identified, and the dissection was continued, elevating the tendon, subperiosteally, from its insertion site at the lesser tuberosity. The dimensions of the footprint were measured superior to inferior, as well as medial to lateral, by a single observer. RESULTS: The insertion of the subscapularis tendon on the lesser tuberosity was trapezoidal in shape. The mean length of the subscapularis tendon footprint was 2.5 cm (range, 1.5 to 3.0 cm). The superior portion of the footprint was the widest part of the subscapularis insertion. The mean width at the most superior aspect of the insertion site was 1.8 cm (range, 1.5 to 2.6 cm). The most inferior aspect of the footprint was much narrower, with a mean width of 0.3 cm (range, 0.1 to 0.7 cm). CONCLUSIONS: The subscapularis insertion footprint has a broad and wide superior attachment that narrows distally to form a trapezoidal shape. We found the mean length of the footprint to be 2.5 cm. The mean superior width of the footprint was 1.8 cm, which was maintained for the upper 60% of the tendon insertion, at which point the footprint began to rapidly narrow to a minimum width of 0.3 cm at its most inferior aspect. The upper 60% of the footprint provided by far the major surface area for tendon insertion, consistent with prior findings of superior load transmission at the superior aspect of the footprint. CLINICAL RELEVANCE: This broad attachment site superiorly is likely important in load transmission. Knowledge of the shape of the footprint of the subscapularis, with a broad superior attachment, makes it easier for the surgeon to perform an accurate anatomic surgical reconstruction of the torn subscapularis. PMID- 17349467 TI - Arthroscopic wrist arthrolysis after wrist fracture. AB - PURPOSE: To evaluate the results of this surgical procedure in patients affected by wrist stiffness after wrist fracture. Criteria for patient inclusion in our preoperative and postoperative study were wrist stiffness with or without pain, decreased grip strength, and unsuccessful results 3 to 6 months after following a rehabilitation program. METHODS: From 1988 to 2003, surgery was performed in 22 patients (16 men and 6 women) with a mean age of 37 years. Radiocarpal, midcarpal, and distal radioulnar joint portals were used in relation to the site of rigidity. Statistical evaluation was performed in all cases. RESULTS: At a mean follow-up of 28 months (range, 9 to 144 months), no complications were documented. One case that was operated on bilaterally successively required an additional right wrist arthroscopic arthrolysis to reach the same level of improvement as that of the contralateral side. Pain was almost absent in all cases (P < .0001), and mean flexion/extension range of motion increased from 84 degrees preoperatively to 99 degrees postoperatively, mean pronation/supination increased from 144 degrees to 159 degrees, and mean grip strength increased from 22 to 28 kg (P < .0001). The mean modified Mayo wrist score improved from 28 to 79 postoperatively (P < .0001), and the mean postoperative score on the Disabilities of the Arm, Shoulder and Hand questionnaire was 21 points. CONCLUSIONS: Arthroscopic wrist arthrolysis is a suitable and promising surgical option for the treatment of wrist rigidity after trauma or surgery. In our series pain and wrist flexion-extension and grip strength significantly improved. The procedure is safe and required a minimal amount of invasive surgery while also permitting the surgeon to identify the precise cause of the intra-articular rigidity and pain. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17349468 TI - Radiographic measurements of the intercondylar notch: are they accurate? AB - PURPOSE: The purpose of this study was to evaluate the accuracy of radiographic measurements of the intercondylar notch. METHODS: Radiographs of 10 cadaveric knees were obtained via the 3 methods reported in the literature (Holmblad 45 degree, Holmblad 70 degree, and Rosenberg views), after removal of the patella and surrounding soft tissues. The anterior outlet of the intercondylar notch of each knee was then outlined with barium paste, and radiography was repeated. A total of 1,770 radiographs were obtained for the 10 knees. Six measurements of the anterior outlet of the intercondylar notch were made from each radiograph and corrected for magnification. Finally, the notch width index was calculated. Caliper measurements were subsequently made of each knee to compare the size of the anterior outlet of the notch with the radiographic measurements with and without barium. RESULTS: There were statistically significant differences in caliper measurements compared with all but one radiographic measurement obtained from the Holmblad 45 degree, Holmblad 70 degree, and Rosenberg views. The radiographs taken with barium outlining the intercondylar notch clearly showed the inability to accurately identify the anterior outlet on radiographs. CONCLUSIONS: Even under optimal conditions, correcting for technique, projection, and magnification, most of the radiographic measurements of the anterior outlet of the intercondylar notch were inaccurate. The notch width index calculated from the Holmblad 70 degree view appears to be the only accurate radiographic measurement. CLINICAL RELEVANCE: This controlled laboratory study shows that clinicians should use caution when basing conclusions on radiographic measurements of the intercondylar notch. PMID- 17349469 TI - An anatomic study of the iliotibial tract. AB - PURPOSE: To identify the structure of the iliotibial tract at knee level, as well as its insertions, layer arrangement, and relationship with other structures of the lateral region of the knee and to compare the findings with available literature. METHODS: Ten detailed anatomic dissections were performed by using incisions as recommended by the literature in fresh cadaver knees identifying the iliotibial tract components. RESULTS: The authors observed an iliotibial tract arrangement in superficial, deep, and capsular-osseous layers. Insertions have been described as follows: at linea aspera, at the upper border of the lateral epicondyle, at the patella, and at Gerdy's tibial tuberculum and across the capsular-osseous layer. CONCLUSIONS: The iliotibial tract (ITT) has important interconnections to the femur, the patella, and the lateral tibia; the iliopatellar band joins the ITT to the patella through the superficial oblique retinaculum and the lateral femoropatellar ligament, and the ITT capsular-osseous layer presents differentiated fibers in an arched arrangement that borders the femoral condyle and inserts laterally to the Gerdy's tubercle. CLINICAL RELEVANCE: The iliotibial tract can be considered as an anterolateral knee stabilizer, particularly its capsular-osseous layer, which, together with the anterior cruciate ligament, constitutes a functional unit forming a spatial "horseshoe" form. The detailed description of the structures forming iliotibial tract plays an important role in the study of knee instabilities. Its important tibial, femoral, and patellar connections are described so that better understanding of tibial femoral instability on the lateral side as well as patellofemoral instability can be achieved and mechanisms of repair can be conceived. PMID- 17349470 TI - Incidence of the anterior meniscofemoral ligament: an arthroscopic study in anterior cruciate ligament-deficient knees. AB - PURPOSE: The purpose of this study was to arthroscopically determine the incidence of the anterior meniscofemoral ligament of Humphry in anterior cruciate ligament (ACL)-deficient knees. METHODS: One hundred forty knees were prospectively evaluated during arthroscopic ACL reconstruction procedures. The mean patient age was 30 years (range, 16 to 45 years), and there were 93 male and 47 female patients. In 69 patients, the right knee was evaluated, and in 71, the left. Inclusion criteria were skeletally mature patients aged under 45 years with isolated ACL injuries. Exclusion criteria were degenerative articular changes, external meniscus injuries, insufficiencies of ligaments other than the ACL, and previous knee surgery. RESULTS: The anterior meniscofemoral ligament of Humphry was present in all of the knees evaluated. CONCLUSIONS: It has been proposed that traumatic and degenerative changes may explain the variation of the reported incidence of the meniscofemoral ligament. In our study in young patients with no degenerative changes, no meniscal injuries or surgery, and no ligament disruption except from the ACL, the anterior meniscofemoral ligament presented as a constant structure. CLINICAL RELEVANCE: Given the high incidence of the appearance of the anterior meniscofemoral ligament, this structure should be preserved during meniscus and ligament surgeries at least until its function and clinical relevance are determined. PMID- 17349471 TI - The fetal anterior cruciate ligament: an anatomic and histologic study. AB - PURPOSE: The purposes of this study were to better understand the fetal development of the anterior cruciate ligament (ACL); to identify the gross anatomy of the ACL; to perform a complete histologic evaluation of the ligament, particularly with respect to the distinction between bundles; and to evaluate ACL length, diameter, cellularity, vascularity, and insertion sites. METHODS: By use of 40 intact knee joints of human fetuses, the gross anatomy of the ACL was inspected under a stereomicroscope (n = 40). The histologic evaluation was performed on the sagittal (n = 20) and transverse (n = 10) sections. RESULTS: The gross observations revealed the presence of 2 distinct bundles: anteromedial (AM) and posterolateral (PL). The femoral origin of each ACL bundle was located in the posterior aspect of the medial surface of the lateral femoral condyle. The footprint of the tibial insertion was ovoid, with the AM bundle located anterior and medial to the PL bundle. The mean length of the ACL was 3.7 mm, the mean width was 1.1 mm, and the mean thickness was 0.9 mm. There was high cellularity, with approximately 5,600 cells/mm2, and intense vascularity. The AM and PL bundles were divided by a well-defined septum. The femoral origin had less dense connective tissue compared with the tibial insertion. CONCLUSIONS: From the time of fetal development, the ACL is composed of 2 bundles, AM and PL. The gross morphology of the ACL in fetuses is similar to that reported in adults; the histology is diverse in cellularity and vascularity. CLINICAL RELEVANCE: This study provides useful information about the anatomy and histology of the fetal ACL. PMID- 17349472 TI - The attachments of the fiber bundles of the posterior cruciate ligament: an anatomic study. AB - PURPOSE: This study aimed to provide data on the sizes and locations of the attachments of the posterior cruciate ligament (PCL) to the tibia and the femur. METHODS: We studied 39 cadaveric knees. The PCL consistently separated into anterolateral (AL) and posteromedial (PM) fiber bundles. Data were obtained to describe the size, position, and center of the PCL bundles related to clock positions and referenced to the center of the circular posterior medial condyle on the femur, as well as to the mediolateral and anteroposterior dimensions of the tibia. The coordinates for the femoral attachment of the PCL bundles were measured parallel to the femoral shaft and to the femoral intercondylar notch roof. RESULTS: A wide variation in shape and size of the PCL attachment was found on the femur, but the pattern of attachment to the tibia was consistent. The tibial attachment of the PCL occupied the posterior intercondylar fossa. The AL bundle's anterior limit was the root of the posterior horn of the medial meniscus, and the PM bundle extended below the joint line by 7 +/- 2 mm (mean +/- SD). On the femur, the AL bundle was centered at 7 +/- 2 mm from the articular cartilage at 10:20 +/- 00:30 o'clock, and the PM bundle was centered at 10 +/- 3 mm from the cartilage at 08:30 +/- 00:30 o'clock. The PCL extended from beyond the 12-o'clock position in all specimens. CONCLUSIONS: Accurate knowledge of the anatomic positions of the bundles of the PCL on both femur and tibia is essential to developing more successful reconstruction techniques. CLINICAL RELEVANCE: The results of this study may be applied to the design of guidance systems for double bundle PCL reconstruction techniques and as a reference for graft tunnel placement in in vitro or clinical follow-up studies. PMID- 17349473 TI - Observations on bone tunnel enlargement after double-bundle anterior cruciate ligament reconstruction. AB - PURPOSE: The purpose of this study was to determine the amount of tibial and femoral bone tunnel enlargement after double-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: Twenty-five consecutive patients undergoing primary double-bundle hamstring ACL reconstruction were included in a prospective case series. Femoral fixation was performed by means of 2 EndoButton CL devices (Smith & Nephew Endoscopy, Andover, MA), and tibial fixation was done with 2 bioresorbable interference screws. Magnetic resonance imaging (MRI) was performed in all patients at a mean of 12.3 months postoperatively. Tunnel enlargement was determined by digitally measuring the widths perpendicular to the long axis of the anteromedial (AM) and posterolateral (PL) tunnels on an oblique coronal and axial plane. The MRI measurements were compared with the intraoperative drill diameter. RESULTS: The mean tibial AM bone tunnel diameter increased from 0.74 to 1.06 cm, and the mean PL diameter increased from 0.60 to 0.89 cm. The mean femoral AM bone tunnel diameter increased from 0.71 to 0.97 cm, and the mean PL diameter increased from 0.58 to 0.85 cm. Bone tunnel enlargement was 43% (P = .001) for both tibial tunnels and 35% (P = .001) versus 48% (P < .001) for the femoral AM bone tunnel versus the PL femoral bone tunnel. On the tibial side, communication of the bone tunnels occurred in 41% of patients. CONCLUSIONS: This study shows significant tibial and femoral bone tunnel enlargement on MRI after 4 tunnel double-bundle ACL reconstruction 1 year postoperatively. In 41% of patients separate tibial bone tunnel measurements were impossible because of tunnel communication caused by intraoperative bone tunnel drilling, screw contact, or postoperative bone tunnel enlargement. On the femoral side, no bone tunnel communication occurred. The short-term clinical results were good and were not influenced by tunnel communication. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17349474 TI - Histologic changes after meniscal repair using radiofrequency energy in rabbits. AB - PURPOSE: Our purpose was to investigate histologic changes in the rabbit meniscus after meniscal repair via radiofrequency energy (RFE). METHODS: Twenty Japanese white rabbits underwent bilateral knee arthrotomies, and a longitudinal tear was made in the avascular area of both medial menisci. On the right knees, RFE treatment (60 degrees C and 40 W) was performed on the femoral surface of the meniscal tear in monopolar mode. On the left knees, the meniscus was left untreated as a control. The rabbits were killed at 0, 1, 2, 4, or 12 weeks after surgery, and all medial menisci were examined histologically. The expression of autocrine motility factor in meniscal fibrochondrocytes was examined by immunohistochemical analysis. RESULTS: Histologic examination at baseline showed fusion of collagen fibers in the tear. Failure of fusion was found in 2 of 4 menisci at 2 weeks and 1 of 4 menisci at 4 and 12 weeks. One week after surgery, the specimens showed an acellular area as a result of fibrochondrocyte death. The acellular area expanded deeper until 4 weeks and was reduced at 12 weeks. On the femoral surface of the RFE-treated area, fibroblast proliferation was found at 2 weeks, and fibroblasts had invaded into the meniscus tissue from the meniscal surface at 12 weeks. Immunohistochemical analysis showed that the expression of autocrine motility factor in RFE-treated menisci was significantly higher than that in control menisci from 1 to 12 weeks. CONCLUSIONS: RFE treatment at 60 degrees C and 40 W fused the collagen fiber in the meniscal tear in rabbits just after surgery. After RFE treatment, an acellular area developed as a result of fibrochondrocyte damage. RFE caused fibroblast proliferation at 2 weeks. The acellular area was reduced by cell repopulation at 12 weeks. CLINICAL RELEVANCE: RFE may induce fibroblast proliferation for meniscal repair. PMID- 17349475 TI - Arthroscopic proximal realignment of the patella for recurrent instability: report of a new surgical technique with 1 to 7 years of follow-up. AB - PURPOSE: Our purpose was to study the 1- to 7-year results of a new arthroscopic technique for recurrent lateral patellar dislocation or subluxation. METHODS: The study group included 38 knees in 37 patients treated over a period of 7 years; 36 knees in 35 patients were available for review (2 were lost to follow-up). There were 26 female and 9 male patients. All patients were evaluated at a mean follow up of 51 months (range, 1 to 7 years). The indications for surgery were recurrent dislocation in 23 knees and recurrent subluxation in 13 knees. Arthroscopic evaluation and lateral release was carried out routinely via 4 portals. A fifth medial patellar portal was used for medial plication with 3 to 7 nonabsorbable sutures. This surgical technique of realignment of the patella was first used in 1994. RESULTS: At final follow-up, the median Lysholm score improved from 17 to 70. The results were excellent or good in 28 of 36 knees (78%), fair in 4 (11%), and poor in 4 (11%). Subjective improvement was reported by 89% of patients. CONCLUSIONS: Arthroscopic realignment of the patella is a procedure with less morbidity and faster rehabilitation, and the results are comparable to, if not better than, those of the established open procedures. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17349476 TI - Knee chondral lesions: incidence and correlation between arthroscopic and magnetic resonance findings. AB - PURPOSE: To determine the incidence and morphologic characteristics of knee chondral lesions found at arthroscopy and their correlation with magnetic resonance imaging (MRI). METHODS: This is a prospective study on 190 consecutive knee arthroscopic procedures performed between March 2003 and February 2004 by the same surgical team. The study group's age average was 34.8 years (14 to 77 years). The indication for surgery included anterior cruciate ligament tears, meniscal tears, and anterior knee pain. Patients without a preoperative MRI study were excluded. MRI reports were performed by qualified radiologists in all the cases. Chondral lesions were classified according to the International Cartilage Repair Society (ICRS) classification and were included in a database along with the MRI reports. The results were analyzed statistically with analysis of variance, Pearson, kappa, and chi-square tests. RESULTS: One hundred fifteen chondral lesions in 82 patients were found during the arthroscopic procedure. Most of them were single lesions (72%) located on the medial femoral condyle (32.2%) or medial patellae (22.6%); 62.6% of the lesions were classified as ICRS type 2 or 3-A, with an average surface of 1.99 cm2. We found a significant direct correlation between the patient's age and the size of the lesion (P = .001). MRI sensitivity was 45% with a specificity of 100%. The sensitivity increased with deeper lesions (direct relation with the ICRS classification). Our results showed a statistical power of 100%. CONCLUSIONS: Although unenhanced MRI using a 1.5 Tesla magnet with conventional sequences (proton density-weighted, T1-weighted, and T2-weighted) is most accurate at revealing deeper lesions and defects at the patellae, our study shows that a considerable number of lesions will remain undetected until arthroscopy, which remains the gold standard. LEVEL OF EVIDENCE: Level III, diagnostic study of nonconsecutive patients. PMID- 17349477 TI - Biodegradable shoulder anchors have unique modes of failure. AB - Biodegradable suture anchors have facilitated and revolutionized arthroscopic tissue-to-bone repair, especially in the shoulder. However, the anchor is but a part of the repair construct, which also includes a suture, tied in a knot, that attaches the tissue (tendon or labrum) to bone. Bioabsorbable anchors may result in loose bodies. Two cases are reported as sentinel events highlighting this potential risk. In the first case, combining a nonabsorbable suture (forming the anchor eyelet) with an anchor body made from rapidly degrading copolymer resulted in the suture becoming a loose body as the anchor body reabsorbed. In the second case, a portion of the eyelet and upper screw thread, itself composed of a biodegradable copolymer, became a loose body as the anchor absorbed, perhaps because the eyelet became proud with regard to the host bone during cyclic loading. Biodegradable anchors offer many advantages over metal anchors but do not eliminate the risk of a glenohumeral loose body. Unexpected postoperative symptoms such as painful catching, popping, or "squeaking" may indicate a glenohumeral loose body and warrant an arthroscopic evaluation. In the future, improved shoulder suture anchor design may lower the risk of this complication. PMID- 17349478 TI - Single-portal SLAP lesion repair. AB - SLAP lesions are increasingly being recognized as a common cause of shoulder pain. Because an intact superior labral complex is required for peak performance of the shoulder, it is critical that all arthroscopic surgeons are able to recognize and repair these injuries. The most common method of repair involves at least 2 additional portals. The area of repair can become quite crowded, and the method can be challenging at times. A simple and highly reproducible technique is described. This technique requires only an anterior portal for suture management and no special instrumentation. A 5-mm anterior portal is established along with a standard posterior portal. A spinal needle is inserted from the anterior lateral aspect of the acromion to identify the most desirable location for the suture anchor. After placement of the suture anchor, a second spinal needle is placed in the area of the subclavian portal. This needle is passed through the base of the biceps origin. PDS suture (Ethicon, Somerville, NJ) is placed through the needle and captured with a standard grasper. Before the needle is removed, a loop grasper or crochet hook is used to locate the needle. This prevents the suture from getting caught in hypertrophic tissue. A standard switching technique is then performed, and both sutures are brought out of the anterior portal and tied. This technique is simple and reproducible and requires no special instrumentation. PMID- 17349479 TI - Osteoarticular allograft transplantation for large humeral head defects in glenohumeral instability. AB - During traumatic anterior shoulder dislocation, significant derangement of normal anatomy occurs. Open and arthroscopic techniques alike have emphasized anatomic reconstruction of anterior capsulolabral structures while often neglecting associated osteoarticular pathology. Recent studies have shown that failure rates after Bankart repair are dramatically higher in the presence of large glenohumeral bone defects, yet little has been written about how to best address these lesions. Historically, these patients will undergo multiple procedures culminating with nonanatomic solutions to constrain the humeral head (coracoid transfer or open capsular shift). Significant loss of motion yields unacceptable results in a high-demand athletic population. We present a new approach to athletic, highly functional patients with recurrent anterior instability and large humeral head defects (Hill-Sachs lesion). Anterior capsulolabral pathology is addressed arthroscopically, and the Hill-Sachs lesion is then addressed via a limited posterior approach to the humeral head. Osteoarticular allograft transplantation is performed by use of a single plug to fill the defect. As described, this procedure can be performed in a single operative setting or as a staged procedure for those patients who still have subjective subluxation as a result of continued engagement of a large humeral head defect after Bankart repair. Importantly, our posterior approach does not require takedown of the anterior capsulolabral repair to address the bone defect. We have performed this procedure in a 19-year-old enlisted US Navy seaman, with excellent short-term results. At 1-year of follow-up, he has returned to full active military duty without restriction. PMID- 17349480 TI - Posterior cruciate ligament reconstruction with a single-sling technique using a tibialis anterior tendon allograft. AB - Reconstruction of the posterior cruciate ligament (PCL) has been performed in various ways. Recent biomechanical tests revealed that a double-bundle graft with a 2-tunnel technique is more likely to restore normal knee stability throughout the full range of knee motion. Several techniques using double-bundle grafts have been implemented for PCL reconstruction; however, each technique has its own advantages and disadvantages. To provide a simplified surgical technique and minimize its inherent complications, the purpose of this study was to introduce a novel technique of arthroscopic PCL reconstruction using an allogeneic tibialis anterior tendon and forming a single sling. PMID- 17349481 TI - A view from above: a modified Patel's medial midpatellar portal for anterior cruciate ligament arthroscopic surgery. AB - The use of flexible positions based on the surgeon's need to address specific pathology has been advocated in arthroscopic surgery. In this report we reappraise the midpatellar portals popularized by Patel and present a technique modification of the medial midpatellar portal (mMPP) focusing on its use in anterior cruciate ligament primary and revision arthroscopic surgery. The modified mMPP is established under arthroscopic control from a high anterolateral portal. Its location is more proximal than the original Patel's mMPP. The nearly vertical orientation of the arthroscope and its proximity to the midline offer a wider and almost face-to-face visualization of the intercondylar notch in the coronal plane, which would provide advantages over standard portals. The anteromedial and anterolateral portals may both be used as working portals without crowding because the arthroscope is cranially located. The need to perform notchplasty is reduced, minimizing bleeding from trabecular bone. Aggressive soft-tissue processing in the intercondylar notch to improve visualization is seldom required. The recipient site is less devascularized, which may promote autograft healing. The modified mMPP may also facilitate femoral tunnel placement and setting of an interference screw. It is safe and reproducible and may add to the diagnostic and working capabilities of the knee arthroscopist. PMID- 17349482 TI - Three-portal technique for anterior cruciate ligament reconstruction: use of a central medial portal. AB - Standard endoscopic reconstruction of the anterior cruciate ligament (ACL) is performed with the use of 2 arthroscopic portals. The surgical error most commonly associated with ACL reconstruction is improper positioning of the tunnel. Errors in femoral tunnel position may be related to poor visualization of the lateral wall. When anatomic double-bundle ACL reconstruction is performed, proper visualization of the lateral wall is essential to ensure correct placement of both tunnels. We propose the use of a central portal, in addition to more standard anterolateral and anteromedial portals, to enhance visualization of the lateral wall. In addition, the arthroscope can be moved interchangeably throughout the portals during the procedure for improved viewing during specific steps. An accessory anteromedial portal placed inferiorly and medially allows placement of the femoral tunnels while providing a high central anteromedial portal for best visualization of the lateral wall. As a result, no notchplasty is required, and a more anatomic reconstruction can be performed. PMID- 17349483 TI - Anterior cruciate ligament graft preparation: a new and quick alternative to the whipstitch. AB - Anterior cruciate ligament reconstruction is a common procedure in orthopaedic practice. Hamstring autograft is increasingly becoming the graft of choice; however, there is little consensus as to the best method of graft preparation and, in particular, the efficacy of the use of a whipstitch with all tibial fixation systems. We propose a new, quick, and economical method of preparing the hamstring graft that involves securing a double loop of suture material around the tendon. This is achieved by passing a loop of No. 2 braided suture under the tendon; the free suture ends are then subsequently passed through the loop twice and tightened. This "loop-the-loop" traction suture allows the surgeon to apply adequate traction to the graft for tensioning while not compromising graft fixation. This new technique is faster than conventional whipstitching and has cost savings, because no needles are necessary. It is of particular help when using a central 4-quadrant sleeve-and-screw fixation device. PMID- 17349484 TI - Combined posterior Bankart lesion and posterior humeral avulsion of the glenohumeral ligaments associated with recurrent posterior shoulder instability. AB - Recurrent posterior glenohumeral instability is uncommon and is often misdiagnosed. Damage to the posterior capsule, posteroinferior glenohumeral ligament, and posterior labrum have all been implicated as sources of traumatic posterior instability. We describe a case of traumatic recurrent posterior instability resulting from a posterior Bankart lesion accompanied by posterior humeral avulsion of the glenohumeral ligaments. The Bankart lesion was repaired using a single arthroscopic suture anchor at the glenoid articular margin. The posterior humeral avulsion of the glenohumeral ligaments was addressed with 3 suture anchors placed at the capsular origin at the posterior humeral head. Using these anchors, the posterior capsule was advanced laterally and superiorly for a secure repair. Arthroscopic anatomic reconstruction of both lesions resulted in an excellent clinical outcome. PMID- 17349485 TI - Combined intra- and extra-articular arthroscopic treatment of entrapment neuropathy of the infraspinatus branches of the suprascapular nerve caused by a periglenoidal ganglion cyst. AB - Entrapment neuropathy of the suprascapular nerve with pain and weakness of the affected shoulder is a rare clinical entity for which several treatment modalities have been reported. Instead of trying to evacuate the cyst from within the joint, the cyst was approached through the subacromial space after subacromial bursectomy, exposure of the spinoglenoid notch, and insertion of a small retractor through an additional posterior portal. This allowed retraction of the infraspinatus muscle together with the inferior branch of the suprascapular nerve for better visualization. After localization of the cyst and nerve, the membrane was incised and the entire viscous contents could be aspirated with a shaver. The intra-articular area of labral detachment was then repaired like a posterior aspect of a SLAP II lesion. The technique described combines the advantages of open and arthroscopic surgery, allowing one to address the underlying intra-articular pathology, completely evacuate the ganglion cyst, and protect the suprascapular nerve. PMID- 17349486 TI - Intraoperative anterior cruciate ligament graft contamination. AB - Intraoperative anterior cruciate ligament graft contamination is a rare but potentially devastating occurrence for any surgeon to encounter. Most instances in our experience have happened when a surgeon first enters practice or is operating in a new environment with new staff. Based on the currently available literature and the senior author's personal experience with 3 cases, intraoperative cleansing of the graft followed by implantation is a reasonable option. The protocol used successfully in these 3 cases includes getting the graft off of the floor immediately, removing any suture material in the graft, cleansing the graft for 15 to 30 minutes each in chlorohexidine and triple antibiotic solution, followed by a normal saline rinse. All graft sutures should then be replaced. The graft should then be resized and the tibial and femoral tunnels adjusted if needed. After implantation of the graft, additional intraoperative and postoperative intravenous antibiotic and/or oral antibiotic administration is also recommended for the first 1 to 2 weeks. Close clinical follow-up is also very important the first 6 weeks postoperatively and should include candid communication with the patient and family. PMID- 17349487 TI - The Duncan loop: all knots and tangles. PMID- 17349488 TI - Magnetic resonance imaging for patellofemoral malalignment. PMID- 17349490 TI - Midazolam as adjunct therapy to morphine to relieve dyspnea? PMID- 17349492 TI - Bone marrow biopsy symptom control and palliative care consultation. PMID- 17349493 TI - Comparing hospice and nonhospice patient survival among patients who die within a three-year window. AB - There is a widespread belief by some health care providers and the wider community that medications used to alleviate symptoms may hasten death in hospice patients. Conversely, there is a clinical impression among hospice providers that hospice might extend some patients' lives. We studied the difference of survival periods of terminally ill patients between those using hospices and not using hospices. We performed retrospective statistical analysis on selected cohorts from large paid claim databases of Medicare beneficiaries for five types of cancer and congestive heart failure (CHF) patients. We analyzed the survival of 4493 patients from a sample of 5% of the entire Medicare beneficiary population for 1998-2002 associated with six narrowly defined indicative markers. For the six patient populations combined, the mean survival was 29 days longer for hospice patients than for nonhospice patients. The mean survival period was also significantly longer for the hospice patients with CHF, lung cancer, pancreatic cancer, and marginally significant for colon cancer (P=0.08). Mean survival was not significantly different (statistically) for hospice vs. nonhospice patients with breast or prostate cancer. Across groups studied, hospice enrollment is not significantly associated with shorter survival, but for certain terminally ill patients, hospice is associated with longer survival times. The claims-based method used death within three years as a surrogate for a clinical judgment to recommend hospice, which means our findings apply to cases where a clinician is very sure the patient will die within three years, and it points to the need to validate these findings. PMID- 17349494 TI - Living with hope: initial evaluation of a psychosocial hope intervention for older palliative home care patients. AB - The overall purpose of this study was to evaluate the effectiveness of a psychosocial supportive intervention called the "Living with Hope Program" (LWHP) in increasing hope and quality of life for older adult, community-living, terminally ill cancer patients. Using a mixed method concurrent nested experimental design, 60 terminally ill cancer patients over the age of 60 years were randomly assigned to a treatment group and a control group. Baseline hope (Herth Hope Index [HHI]) and quality-of-life scores (McGill Quality of Life Questionnaire [MQOL]) were collected at the first visit in the patients' homes by trained research assistants. Those in the treatment group received the LWHP, which consisted of viewing an international award-winning video on hope and a choice of one of three hope activities to work on over a one-week period. The control group received standard care. Hope and quality-of-life data were collected one week later from both groups. Qualitative data using open-ended hope questions were collected from the treatment group. Patients receiving the LWHP had statistically significant higher hope (U=255, P=0.005) and quality-of-life scores at Visit 2 (U=294.5, P=0.027) than those in the control group. Qualitative data confirmed this finding, with the majority (61.5%) of patients in the treatment group reporting the LWHP increased their hope. This preliminary evaluation of the effectiveness of the LWHP suggests that it may increase hope and quality of life for older terminally ill cancer patients at home. PMID- 17349495 TI - Symptom management with massage and acupuncture in postoperative cancer patients: a randomized controlled trial. AB - The level of evidence for the use of acupuncture and massage for the management of perioperative symptoms in cancer patients is encouraging but inconclusive. We conducted a randomized, controlled trial assessing the effect of massage and acupuncture added to usual care vs. usual care alone in postoperative cancer patients. Cancer patients undergoing surgery were randomly assigned to receive either massage and acupuncture on postoperative Days 1 and 2 in addition to usual care, or usual care alone, and were followed over three days. Patients' pain, nausea, vomiting, and mood were assessed at four time points. Data on health care utilization were collected. Analyses were done by mixed-effects regression analyses for repeated measures. One hundred fifty of 180 consecutively approached cancer patients were eligible and consented before surgery. Twelve patients rescheduled or declined after surgery, and 138 patients were randomly assigned in a 2:1 scheme to receive massage and acupuncture (n=93) or to receive usual care only (n=45). Participants in the intervention group experienced a decrease of 1.4 points on a 0-10 pain scale, compared to 0.6 in the control group (P=0.038), and a decrease in depressive mood of 0.4 (on a scale of 1-5) compared to +/-0 in the control group (P=0.003). Providing massage and acupuncture in addition to usual care resulted in decreased pain and depressive mood among postoperative cancer patients when compared with usual care alone. These findings merit independent confirmation using larger sample sizes and attention control. PMID- 17349496 TI - Ecological momentary assessment of fatigue in patients receiving intensive cancer therapy. AB - The ability to accurately assess the incidence, intensity, and timing of cancer related fatigue is important for clinicians attempting to manage this symptom and for researchers evaluating interventions to reduce or alleviate fatigue. This methodological report describes our experiences with ecological momentary assessment (EMA) and discusses its applicability for capturing real-time, real world assessments of fatigue in patients receiving intensive cancer therapy. This methodological report is part of a larger study examining fatigue and physical activity before and after hematopoietic stem cell transplantation (HSCT). A prospective, repeated measures design was used to assess changes in fatigue three days before and three days after intensive cancer therapy and HSCT. A convenience sample (n=20 before HSCT, and n=17 after HSCT) was drawn from two Midwestern academic medical centers. Real-time fatigue was measured with a single-item, global, fatigue intensity scale. Multiple fatigue assessments were conducted throughout each study day. Data were collected electronically, facilitating examination of compliance. Subjects responded to fatigue intensity queries 87% of the time before HSCT and 86% after HSCT. Response rates were not unduly influenced by level of fatigue, time of day, or gender. The study findings demonstrate that it is feasible to use computerized EMA to collect self-report fatigue data in acutely ill oncology patients. Most HSCT patients were able to provide real-time fatigue data even when experiencing multiple side effects from the preparatory regimen. EMA is a novel approach that holds substantial promise for investigating fatigue and other cancer symptoms. PMID- 17349497 TI - Development of the paediatric pain profile: role of video analysis and saliva cortisol in validating a tool to assess pain in children with severe neurological disability. AB - The Paediatric Pain Profile (PPP) is a 20-item behavior-rating scale designed to assess pain in children with severe to profound neurological impairment. Three raters independently used the PPP to rate behavior of 29 children (mean age 9.6, SD 5.8) filmed during everyday morning activities. The validation process included assessment of interrater reliability and exploration of the relationship of PPP scores with saliva cortisol concentration. There was substantial agreement between raters. The PPP showed strong association with global pain assessments and differentiated between preselected high- and low-pain groups. PPP score showed moderate correlation with saliva cortisol concentration, but a single child explained the strength of the relationship and overall, saliva cortisol concentrations appeared low. The data provide additional evidence that the PPP is a reliable and valid instrument for pain assessment in neurologically impaired children. Cortisol levels are not a useful criterion for pain in this population and further study of cortisol response to stress/pain in children with severe neurological impairments is needed. PMID- 17349498 TI - Nurses' perceptions of children's pain: a pilot study of cognitive representations. AB - Despite advances in pain assessment and management, hospitalized children continue to report high levels of pain intensity. Untreated pain can have deleterious effects on multiple body functions, resulting in delayed recovery, prolonged hospitalization, and worsening illness. Prior research demonstrates that nurses administered analgesia that was less than amounts recommended by standards and less than that available by physician order. This study was conducted to better understand how nurses think about and respond to children's pain by examining pediatric nurses' cognitive representations (CRs) and comparing the contents of CRs with standards of practice and with management decisions in case studies. Kaplan's theory of CR guided the research. Twenty registered nurses' CRs were measured by the Conceptual Content Cognitive Map open-ended technique. Descriptive and content analyses revealed that participants have rich and diverse CRs of children's pain. Cognitive map content items (294) were coded by investigators as belonging to an assessment (63%) or management (37%) domain. Items were further coded into multiple subgroups in each domain. For assessment, 65% of participants included the use of children's self-report of pain in their maps while 80% included behavioral manifestations; 50% included both. For management, 75% of participants identified pharmacological approaches, 60% identified nonpharmacological approaches, and 35% identified family involvement; 25% identified all three approaches. Indicators in participants' cognitive maps suggest there may be a relationship between nurses' CRs and choice of analgesic administration. Findings provide the direction for future education and research to improve children's pain relief. PMID- 17349499 TI - Optimism predicting daily pain medication use in adolescents with sickle cell disease. AB - This study examined the influence of optimism on pain medication use in adolescents with sickle cell disease (n=27; 18 females, 9 males). Participants completed a baseline measure of optimism and an average of 100 daily-diary assessments of pain severity and medication use. Results indicated that adolescents who experienced more severe pain used more analgesic and opioid medications. Optimism was a significant moderator of the relation between pain and opioid-medication use. At medium and high levels of optimism, pain was positively related to opioid use, but at low levels of optimism, the same relation was not present, suggesting that more optimistic adolescents are better able to match their medication use to their pain severity. Future research should examine how other psychosocial factors might influence pain medication use in adolescents and adults who experience pain, and clinicians should take into account psychosocial factors when working with pain populations. PMID- 17349500 TI - A brief cognitive-behavioral intervention reduces hospital admissions in refractory angina patients. AB - Chronic refractory angina is an increasingly prevalent, complex chronic pain condition, which results in frequent hospitalization for chest pain. We have previously shown that a novel outpatient cognitive-behavioral chronic disease management program (CB-CDMP) improves angina status and quality of life in such patients. In the present study of 271 chronic refractory angina patients enrolled in our CB-CDMP, total hospital admissions were reduced from 2.40 admissions per patient per year to 1.78 admissions per patient per year (P<0.001). The rising trend of total hospital bed day occupancy prior to enrollment fell from 15.48 days per patient per year to a stable 10.34 days per patient per year (P<0.001). There were 32 recorded myocardial infarctions prior to enrollment compared to eight in the year following enrollment (14% vs. 2.3%, P<0.001) and overall mortality was lower that comparable groups treated with surgery. This study shows that educating patients and demystifying angina using a brief outpatient CB-CDMP produces an immediate and sustained reduction in hospital admission costs that represents a major potential health care saving. This benefit accrues in addition to the known effects of CB-CDMP on symptoms and quality of life. These data suggest that a CB-CDMP approach to symptom palliation represents a low cost alternative to palliative revascularization. PMID- 17349501 TI - Hospital deaths in Sweden: are individual socioeconomic factors relevant? AB - As the proportion of deaths in hospital falls, it is important to ensure that social disadvantage has no role in determining place of death. This study investigated the association between individual sociodemographic factors and deaths in hospitals for the population of Stockholm County, Sweden, using linked population registers. In 2002, 14,517 (87%) of the 16,617 adult decedents in Stockholm County had contact with health services in the three years before they died. Twenty-two percent (3,210) of these deaths were in hospitals. Individual income, education, country of birth, and gender had no influence on likelihood of hospital death in multivariate analyses. Decedent characteristics associated with higher chance of hospital death included older age, being married, diagnosis of heart disease, and contact with ambulatory services (not family practitioners) in the three years before death. Cancer patients were no more or less likely than those without cancer to die in hospital. In health systems wishing to reduce an already low proportion of deaths in acute hospitals, enhancing palliative and social support for older patients and people with noncancer diagnoses may merit attention. PMID- 17349502 TI - Low use of durable medical equipment by chronically disabled elderly. AB - Assistive devices are a common effective approach to mitigating the effects of chronic disability. The Medicare Durable Medical Equipment (DME) benefit is intended to provide patients with equipment to meet the challenges of health related disability; the penetrance of benefit among the disabled is unclear. A nationally representative cohort of 4,687 community-dwelling elderly enrolled in fee-for-service Medicare (part of the Medicare Current Beneficiary Survey in 1999 and 2000) assessed self-reported disability, and receipt of Medicare DME was assessed through linked claims. Fewer than half the chronically disabled, and less than one-quarter of the newly disabled, received any DME from Medicare. These data suggest underuse of the benefit by the disabled elderly. PMID- 17349503 TI - Yoga for women with metastatic breast cancer: results from a pilot study. AB - Metastatic breast cancer (MBC) remains a terminal illness for which major treatment advances are slow to appear, and hence it is crucial that effective palliative interventions be developed to reduce the cancer-related symptoms of women with this condition during the remaining years of their lives. This pilot/feasibility study examined a novel, yoga-based palliative intervention, the Yoga of Awareness Program, in a sample of women with MBC. The eight-week protocol included gentle yoga postures, breathing exercises, meditation, didactic presentations, and group interchange. Outcome was assessed using daily measures of pain, fatigue, distress, invigoration, acceptance, and relaxation during two preintervention weeks and the final two weeks of the intervention. Thirteen women completed the intervention (mean age=59; mean time since diagnosis=7 years; two African American, 11 Caucasian). During the study, four participants had cancer recurrences, and the physical condition of several others deteriorated noticeably. Despite low statistical power, pre-to-post multilevel outcomes analyses showed significant increases in invigoration and acceptance. Lagged analyses of length of home yoga practice (controlling for individual mean practice time and outcome levels on the lagged days) showed that on the day after a day during which women practiced more, they experienced significantly lower levels of pain and fatigue, and higher levels of invigoration, acceptance, and relaxation. These findings support the need for further investigation of the effects of the Yoga of Awareness Program in women with MBC. PMID- 17349504 TI - Topical agents for the management of musculoskeletal pain. AB - The recent recognition of the magnitude of cardiovascular risk of both nonselective nonsteroidal anti-inflammatory drugs and COX-2 selective inhibitors, in addition to the persistent concerns about the use of opioids, has brought increased attention to nonsystemic, topical analgesics. These agents have a favorable safety profile and there is increasing evidence indicating their efficacy for a variety of pain disorders. The use of topical analgesics in the treatment of the most prevalent musculoskeletal pain syndromes is described, with a focus on mechanisms for drug delivery and clinical trials data. PMID- 17349505 TI - Multimodal approaches to the management of neuropathic pain: the role of topical analgesia. AB - Because of their localized activity and low systemic absorption, topical analgesics have a favorable safety profile and a low risk for drug-drug interactions. There is a growing body of evidence on the efficacy and safety of these agents in a variety of pain disorders, including the most prevalent neuropathic pain conditions. The molecular basis for the usage of peripheral analgesics in neuropathic pain and the available clinical trial evidence for a wide variety of topical agents are reviewed. PMID- 17349508 TI - Resilience and developmental psychopathology. AB - Humans vary to a great extent in their ability to adapt to adverse experiences. Resilience reflects the positive end of this spectrum of adaptation and maladaptation in response to risk exposure. Some individuals, despite being faced with the most pernicious of adversities, manage to avoid psychologic collapse and to maintain healthy adjustment. For decades, researchers and clinicians have searched for the correlates and causes of resilience, and several comprehensive reviews of these efforts are available. This article provides an overview of resilience research and selectively summarizes recent advances in the field, with a particular focus on a developmental psychopathology perspective. This article highlights some of the challenges to resilience research and uses the example of maltreatment to illustrate some of these issues. PMID- 17349509 TI - Cultural understandings of resilience: roots for wings in the development of affective resources for resilience. AB - The authors examine one of the precursors of positive development: attachment. Attachment and the positive growth it portends for populations of children under stress underpins positive developmental outcomes now termed "resilience." Resilience may be understood as a process of adaptation to adversity that is scaffolded by environmental, cultural, social, psychologic, and physiologic processes. The authors focus on two methodologically different approaches to studying attachments that contribute to resilient functioning at two different phases of development (toddlerhood and adolescence). The authors examine the cultural differences found in manifestations of resilience in different countries and cultures. Organized around this theme of attachment, the authors identify adaptive factors in resistance to risk from adverse circumstances. The authors strive to identify how the adaptation involved in attachment relations can protect against vulnerability. The authors conclude with a description of the processes that might help us to understand situational, experiential, and personal resources that intersect to protect the developing individual against assaults on normal growth and development. PMID- 17349510 TI - Measuring protective factors: the development of two resilience scales in Norway. AB - The prevalence of mental disorders among adults and adolescents is high, and World Health Organization estimates indicate an increase in the near future, especially in depressive disorders. Clarifying the development of psychopathology and preservation of mental health is of the utmost importance. Identification of influential protective and vulnerability factors is a primary focus. The development of valid and reliable operationalizations of protective factors may be one step toward determining which factors are important and influential in preserving good mental health and preventing the development of psychopathology. This article summaries of the development of an adult and an adolescent scale for measuring protective factors associated with resilience. PMID- 17349511 TI - Genetically informative designs in the study of resilience in developmental psychopathology. AB - The study of resilience, defined here as the ability to recover from a prior illness or the capacity to remain well in the face of extraordinary genetic or environmental risk factors, is the focus of this article. We believe that to study resilience in the domain of developmental psychopathology it is necessary to use genetically informative strategies. Extending this argument to the study of resilience (eg, why some kids recover) is the focus of last part this article and our research strategies in the next decade. PMID- 17349512 TI - Brazilian approaches to understanding and building resilience in at-risk populations. AB - In this article, the authors present studies related to the concept of resilience as they emerged in Brazil. First, the article describes current definitions and some methodologic approaches developed and used by Brazilian researchers in their investigations. Then it focuses on studies conducted in different parts of the country, emphasizing the resilience process in children, youth, and families of different at-risk conditions. Finally, the article illustrates the applications of those findings on intervention, prevention, social policies, and clinical practice. PMID- 17349513 TI - Uphenyo ngokwazi kwentsha yasemalokishini ukumelana nesimo esinzima: a South African study of resilience among township youth. AB - This article presents the concept of resilience as it is understood by South African township youth and the role that Life Orientation (a compulsory school subject that aims at equipping youth to deal with and master their difficult circumstances) plays in developing and sustaining their resilience. The implication for practice is clear: Resilience is a dynamic, interactive process that can be nurtured by stakeholders who are cognizant of the importance of cultural and basic systemic components. PMID- 17349514 TI - Chinese approaches to understanding and building resilience in at-risk children and adolescents. AB - This article discusses the prevailing Chinese belief systems that have bearings on the perception and practices of promoting resilience among children and youth in a major city in China. It briefly describes a huge social intervention program entitled "Understanding the Adolescent Project" to combat the problems among grade 7 students identified as adolescents at risk from 2001 to 2004 in Hong Kong Special Administrative Region. A critical review of the problems encountered by social workers in the delivery of the program is presented to support the move to provide the preventive program for grade 4 students with clinical symptoms on a screening tool for identification of at-risk status. Starting in 2005, a large scale positive youth development program was being developed for all secondary one to three (grades 7 to 9) students. Encouraging results of the evaluation studies demonstrated the effectiveness of this new preventive program, entitled Positive Adolescent Training through Holistic Social Programs. PMID- 17349515 TI - Understanding the findings of resilience-related research for fostering the development of African American adolescents. AB - African American youth face a number of challenges to prosocial development that the majority of American youth never encounter. Despite this, the research clearly documents that African American youth often are resilient in the face of these challenges. This article explores various factors associated with resilience in African American children and their implications for practitioners. An ecologic framework described by Bronfenbrenner is used as an organizing framework for understanding interventions at the micro-, mezzo-, and exo-system levels. In this article, the importance of identity formation, maintenance of social networks, and exposure to safe and supportive environments is expressed in conjunction with recommendations for practitioners. Practitioners are encouraged to stress the promotion of ethnic and racial identity and self-efficacy with the youth and their family and the involvement of the youth and family in meaningful activities through local community centers, schools, churches, and other organizations serving youth. A case study of an African American girl, from age 16 into adulthood and motherhood, is presented to illustrate the interplay between protective and risk factors. PMID- 17349516 TI - Personal and interpersonal characteristics related to resilient developmental pathways of sexually abused adolescents. AB - Childhood sexual abuse is a prevalent and important social problem. In this article the authors' main objective is the exploration of resilience among sexually abused adolescents under child protection services care in Quebec, Canada. The introduction provides an overview of the impact of childhood sexual abuse and conceptualizations of trauma, resilience, recovery, and factors linked to resilience profiles. The remainder of the article discusses a study of resilience and factors predicting resilience over a 5-month period for a sample of 86 teenage girls under child protection services care. PMID- 17349517 TI - Cognitive vulnerability to depression: exploring risk and resilience. AB - Scientific progress in risk research does not always translate to progress in resilience research. One explanation for the disconnect between risk and resilience research is inadequate theory construction in psychopathology. In this article, the authors argue that improved theory construction can help bridge the gap between risk and resilience. An example from the field of depression is used to illustrate how well constructed theories of risk can be used to develop and test preventions and interventions that bolster resilience. This article concludes with a discussion about the need for cross-cultural research on risk and resilience, which exemplifies a variety of environmental and genetic risk and resilience factors encountered by different populations and cultures. PMID- 17349518 TI - Understanding the relationship between resiliency and bullying in adolescence: an assessment of youth resiliency from five urban junior high schools. AB - Much of the debate on youth bullying and violence focuses upon interventions with instigators of the violence or on broad-based general prevention strategies that may or may not be geared toward individual school conditions. These strategies frequently take a problem-focused approach that can pathologize behavior and create divisions within schools rather than providing solutions. One of the reasons why this occurs is because it is difficult for educators to gather specific information related to bullying and aggressive behaviors in their school or district. This article provides an overview of a comprehensive assessment tool, the Youth Resiliency: Assessing Developmental Strengths questionnaire, developed by Resiliency Canada, that is being used by educators and other concerned stakeholders to understand the dynamics of resiliency to bullying and other aggressive behavior patterns. The article also provides information for understanding the resiliency factors and strengths related to a range of connected behaviors and attitudes of young people who engage in bullying. It also suggests a strength-based approach that can be used by educators, parents, students, and members of the community to promote the development of resiliency through collaborative strategies that address the needs of youth in their school. PMID- 17349519 TI - Nuances in early adolescent developmental trajectories of positive and problematic/risk behaviors: findings from the 4-H study of positive youth development. AB - Using data from the first three waves of data (Grades 5, 6, and 7) from the 4-H Study of Positive Youth Development (PYD), the authors assessed among 1,184 youth (58.5% female) the patterns of change associated with indicators of PYD and of risks/problem behaviors. Results indicated that five PYD trajectories represent change across grades, four trajectories were associated with indicators of internalizing problems, and three trajectories were associated with indicators of externalizing problems. Although theoretical expectations associated with the study of both child and adolescent resilience and PYD led to the expectation that most youth across the early adolescent period would show change marked by the coupling of increases in PYD and decreases in risk/problem behaviors, only about one-sixth of all youth in the sample manifested this particular pattern of change. Other youth remained stable over time, showed increases in PYD and risk, and declined in PYD. The multiplicity of patterns of conjoint trajectories for PYD and risks/problem behaviors constitutes a challenge for both developmental theory and applications aimed at enhancing resilience and positive development among adolescents. PMID- 17349520 TI - Resilience theory and the diagnostic and statistical manual: incompatible bed fellows? AB - As in any scientific undertaking, theoretical orientation and the classification schemas underlying those theories are important to test hypotheses about optimal conditions for fostering positive growth and adaptation. This article explores what conceptual factors prevent the integration of resilience theory and practice into the Diagnostic and Statistical Manual (DSM). We argue that the DSM was a necessary first step toward a general theory of classification because diagnoses in psychiatry needed to be operationalized but that the DSM's inability to evolve as a classification system and to incorporate developmentally sensitive interactional and transactional factors make the DSM categorical approach inadequate for developmental science. Developmental research, based on firm evidence from context-sensitive longitudinal studies analyzing risk and resilience factors, suggests a reconceptualization based on multiple developmental pathways operating dimensionally across the lifespan and intergenerationally. PMID- 17349521 TI - Building strengths through practice-research-policy collaborations. AB - Solving long-standing, sensitive social problems through community-based, collaborative partnerships requires more than rushed policies and program efforts that react to sudden crises. Efforts to support resilient trajectories in children dealing with adversities like peer victimization or adolescents' searching for engagements and identities in communities struggling with a dramatic change in its economic base requires a sustained and coordinated effort based on the best knowledge that we have. But action must not only be knowledge based, it must also be relevant, and the "buy-in" of or "pull from" those who are affected by the action as recipients or as implementers needs to be secured. Collaboration of policy makers, practitioners, and researchers can advance this agenda. Involving decision-makers and knowledge users in the formulation of knowledge has been highlighted as the best predictor for the application of research knowledge. Community-based research can ensure that research results are relevant to a wider audience and thus hasten adoption beyond the immediate communities. PMID- 17349522 TI - Fuzzy thinking on biomarkers. PMID- 17349523 TI - Survival benefit for early hormone ablation in biochemically recurrent prostate cancer. AB - PURPOSE: To determine whether early initiation of androgen ablation in patients with biochemically recurrent prostate cancer, but without clinically evident metastases, is associated with improved overall or disease-specific survival. To describe subgroups, based on PSA kinetics, which are most likely to benefit from early androgen ablation. MATERIALS AND METHODS: A retrospective cohort of 124 patients, who were definitively treated by external beam radiotherapy between 1988 and 1999, and subsequently received androgen ablation for biochemical (92 patients) or clinically metastatic (32 patients) failure, was reviewed. Median follow-up time was 6.2 years. Overall survival, disease-specific survival, and hormonal control were examined and compared for patients whose hormone ablation was started early (prostate-specific antigen [PSA] 7 months) or late in the course of their biochemical failure. RESULTS: All patients had biochemical response to hormone initiation, with a median PSA nadir of 0.05 ng/ml. Early initiation of hormone ablation resulted in statistically significant improvement in all outcome measures. Multivariate analysis indicated that PSA doubling time at hormone initiation was the most consistent predictor of outcome. The 5-year overall survival was 78% for patients whose androgen ablation was initiated at doubling time 7 months. Mean survival improved from 84.9 +/- 4.6 (doubling time 7). Survival for patients started on hormones with doubling time <5 months was similar to that of patients with clinical metastases. CONCLUSIONS: This survival benefit justifies the use of androgen ablation in patients whose doubling time approaches 7 months. A randomized trial is needed to confirm these findings, investigate potential benefit for patients with longer doubling times, and gather data on the morbidity of early hormone ablation, including quality of life issues. PMID- 17349524 TI - Pathologic findings at radical prostatectomy: risk factors for failure and death. AB - BACKGROUND: Failure after radical prostatectomy can occur even out to 25 years after surgery. Therefore, it is important that studies have sufficient follow-up to determine more accurately the risk of failure. We evaluated a large cohort of patients for pathologic findings and risk of failure with a median follow-up of 9.5 years. MATERIAL AND METHODS: Between 1985 and 1995, 719 patients underwent radical prostatectomy for lymph node negative prostate cancer. The prostate was inked and evaluated for: (1) positive bladder neck or urethral margin, (2) positive seminal vesicle, (3) into capsule, (4) through capsule, and (5) positive margin. These were considered positive pathologic findings. RESULTS: Overall, 264 (37%) of the patients had biochemical recurrence. For those patients with failure, median time to biochemical recurrence was 2.4 years. Five and 10-year biochemical failure rates were 28% and 38%, respectively. Pathologic stage of disease significantly (<0.0001) predicted for subsequent failure. If there were no positive pathology findings, the recurrence rate was 25%, compared to 63% for any of the 3 findings. Overall, 212 (29%) of the patients have died. Five and 10 year survival were 91% and 75%, respectively. A total of 45 patients (6%) died of prostate cancer. For patients with negative pathology findings, 3% died as a direct consequence of prostate cancer, compared to 13% if the pathology was positive. Of the patients with positive seminal vesicle, 28% died of cancer. CONCLUSION: Patients with any of the following factors have a risk of failure exceeding 40% and are candidates for studies of adjuvant therapy: seminal vesicle involvement, extension through the capsule, or margin involvement. PMID- 17349525 TI - Growth rates of renal cell carcinoma and oncocytoma under surveillance are similar. AB - OBJECTIVE: Through examining our experience with renal mass surveillance, we hoped to determine factors suggestive of renal cell carcinoma. METHODS: We followed for at least 1 year 41 patients with 47 solid renal masses (mean diameter 2.0 cm, range 0.8-5). Mean surveillance duration was 29 months and was more than 2 years for 23 masses (49%). RESULTS: Overall mean increase in diameter was 0.27 cm/year, but 21 (45%) did not grow, and mean growth rate was 0.5 cm/year in the 26 that did grow. Of the masses, 14 have been treated, 33 continue to be followed, and pathology is known in 16 (34%). Growth was seen in all 6 known oncocytomas (mean 0.52 cm/year), 80% of the 10 biopsy proven renal cell carcinomas grew (mean 0.71 cm/year), but only 12 (39%) of the masses with unknown pathology (0.08 cm/year). There was no factor that distinguished oncocytomas from renal cell carcinomas. In 1 patient, a 3-cm mass that had not changed in size for 6 years doubled in size over 6 months, and metastatic disease developed. CONCLUSIONS: Although growth of most renal masses is slow, some grow quickly, and delayed growth with metastases can occur. No factor distinguished renal cell carcinomas from oncocytomas. Surveillance for renal masses remains an option but must be rigorous and continuous, and is not without risk of progression. PMID- 17349526 TI - Gene expression profile in squamous cell carcinoma of the urinary bladder using complementary deoxyribonucleic acid microarray. AB - To date, molecular evidence studies for bladder cancer, using the microarray technology, are focusing on the transitional cell carcinoma, however, similar fingerprinting studies have rarely been performed on the other molecular phenotypes of bladder cancer, squamous cell carcinoma (SCC). This study was conducted to monitor the gene expression profiles for bilharzial-related SCC of the bladder to be able to compare its data with transitional cell carcinoma microarray data. A total of 17 paired bilharzial urinary bladder SCC specimens and their corresponding normal urothelium were analyzed using the complementary deoxyribonucleic acid microarray hybridization approach to study the molecular basis of the development of SCC of the urinary bladder. Validation of the microarray results was performed using the Northern blotting technique. After supervised analysis of the microarray data, there was at least a 3-fold difference in the expression between SCC of the bladder and normal urothelium in 82 genes. A total of 38 genes were up-regulated in SCC of the bladder, including matrix degradation-related genes, growth factors, different oncogenes, and immunology related genes. Conversely, 44 genes were down-regulated in SCC of the bladder, including integrins, laminins, cadherins, nonmetastatic cell 1 (NM23) and apoptosis-related genes. Our findings can explain the aggressive behavior of SCC of the bladder. Such gene profiling studies will add to our understanding of the mechanisms of carcinogenesis, and may also improve our ability to diagnose and treat bladder cancer. PMID- 17349527 TI - Significance of Aurora-A expression in renal cell carcinoma. AB - The objective of this study was to evaluate Aurora-A expression in human renal cell carcinomas (RCCs) to clarify the clinical significance of Aurora-A expression in this disease. Expression levels of Aurora-A messenger ribonucleic acids and proteins in both normal kidney and RCC specimens obtained from 131 patients undergoing radical nephrectomy were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemical staining, respectively. Various levels of Aurora-A protein expression were noted in 127 of the 131 RCC specimens (96.9%), while only 101 of the 131 normal kidney tissues (77.1%) showed Aurora-A staining. In addition, the expression levels of Aurora-A protein in both normal and RCC specimens were in proportion to those of Aurora-A messenger ribonucleic acids. Aurora-A protein expression in RCC tissues was significantly related to tumor grade, but not with age, gender, tumor size, pathologic stage, or histologic cell type. Cell proliferative activity in RCC specimens was significantly associated with Aurora-A expression, while there was no significant correlation between the apoptotic index and Aurora-A protein expression. Furthermore, there was no significant difference in recurrence-free survival between patients with strong Aurora-A expression and those with weak expression. In conclusion, despite the detection in the majority of RCC tissues, Aurora-A expression failed to show the significant association with major pathologic factors and prognosis in patients with RCC. PMID- 17349529 TI - Testis-specific protein Y-encoded gene is expressed in early and late stages of gonadoblastoma and testicular carcinoma in situ. AB - The testis-specific protein Y-encoded gene (TSPY) is a tandem repeat gene located at the critical region for the gonadoblastoma locus on Y chromosome that predisposes the dysgenetic gonads of intersex individuals to oncogenesis. The expression and molecular properties of TSPY suggest that it is the putative gene for the gonadoblastoma locus on Y chromosome. In this study, we examined the expression of TSPY and other germ cell tumor markers in 4 cases of gonadoblastoma using immunostaining techniques. Our results showed that TSPY expression was closely associated with initiation and various stages of gonadoblastoma development. TSPY protein localized with established germ cell tumor markers, such as the placental alkaline phosphatase, c-KIT, and OCT3/4, in the same tumor cells of both gonadoblastoma and adjacent carcinoma in situ, the precursor for germ cell tumors. These findings support the candidacy of TSPY as the gene for the gonadoblastoma locus on Y chromosome and suggest that TSPY could be a significant marker for these types of germ cell tumors. PMID- 17349528 TI - Expression of insulin-like growth factor-1 receptor in local and metastatic prostate cancer. AB - PURPOSE: The insulin-like growth factor (IGF)-1 receptor is currently being targeted in clinical trials in prostate cancer. Despite this targeting, there are conflicting data on the presence of this receptor in human tumor samples, largely because of differences in technique. MATERIALS AND METHODS: Immunohistochemistry was used to determine the presence of IGF-1 receptor in frozen normal prostate and prostate cancer specimens. Clinical and pathologic parameters were correlated with IGF-1 receptor intensity and frequency of staining. Only 2-3+ staining on a scale of 0-3 was considered positive in this evaluation. RESULTS: IGF-1 receptor was expressed in normal prostate epithelium in 6 of 6 patients without cancer and in morphologically normal epithelium adjacent to tumor cells in 21 of 22 patients with cancer studied. IGF-1 receptor was present in the prostate tumor epithelium of 28 of 28 primary tumors, 3 of 5 locally recurrent androgen-independent tumors, and in 4 of 5 metastatic lymph nodes. Stromal staining patterns were positive in 2 of 28 specimens near benign epithelium compared to 19 of 30 specimens of stroma surrounding tumor epithelium (P < 0.0001, Fisher exact test). Stroma adjacent to Gleason grade >or=7 tumors showed higher intensity staining than that adjacent to lower grade tumors (P < 0.001). Expression of the closely related insulin receptor did not show expression in either normal or cancer epithelium, or in adjacent stroma. CONCLUSIONS: This study using frozen tissue shows widespread IGF 1 receptor expression in normal prostate, prostate cancers, and metastases. These data support investigations into IGF-1 receptor as a therapeutic target in prostate cancer. PMID- 17349530 TI - Pediatric reconstructive techniques in adult urology. PMID- 17349531 TI - Creation of continence mechanisms (Mitrofanoff) without appendix: the Monti and spiral Monti procedures. AB - This is a review of the technique to create a continent catheterizable stoma using the Yang-Monti principle of a transversely tubularized segment of bowel. Pediatric urologists have widely used this technique for years, especially when the appendix is either not available or suitable for use. It provides the surgeon with a reliable, predictable, and durable method for creating a continent catheterizable channel. The indications for its use, principles of construction, and outcomes in a large population of children are described. PMID- 17349532 TI - Technical aspects of abdominal stomas. AB - Continent urinary diversion has gained increasing popularity in the pediatric population during the last few decades. In adults, continent diversions are usually needed to replace a bladder after cystectomy for invasive carcinoma. Subsequently, the creation of functional and cosmetically hidden urinary and cecal abdominal stomas has become an integral part of many urinary reconstructive procedures. These techniques, originally developed for pediatric urinary reconstruction have gained increasing popularity for adult patients in need of a continence procedure. In the current manuscript, we review the technical aspects of site selection, mucocutaneous anastomosis, cosmetic appearance, and management of associated complications. PMID- 17349533 TI - Plastic surgery repair of abdominal wall and pelvic floor defects. AB - Urologists often encounter large perineal and abdominal wall defects, the treatment of which may require close collaboration with the plastic surgeon. These complex defects can be successfully treated using a variety of techniques. Ventral hernias or freshly created abdominal wall defects can be treated with the basic principles of tension-free closure using abdominal wall components separation, synthetic mesh reconstruction, and, more recently, biosynthetic acellular dermis reconstruction. Pelvic floor defects often require flap reconstruction using gracilis flaps, vertical rectus abdominis myocutaneous flaps, or local fasciocutaneous flap. In this article, we seek to familiarize the urologists with the most common techniques used by plastic and reconstructive surgeons in the treatment of these complicated pelvic floor and abdominal wall defects. PMID- 17349534 TI - Malignancy associated with the use of intestinal segments in the urinary tract. AB - Use of intestinal segments for urinary tract reconstruction has become widespread. In these patients, urologists are increasingly encountering malignancies that may be a direct result of this altered milieu. This review attempts to summarize the current literature on cancer in patients with intestinal segments in their urinary tracts. Although the exact etiology for this increased risk of malignancy is still unclear, several theories have been proposed. Many investigators now recommend annual screening in patients who have intestinal segments in contact with urine beginning 10 years after the initial surgery. PMID- 17349535 TI - Do we need a geriatric assessment for a better surgical treatment in older patients with bladder cancer? PMID- 17349556 TI - Legal issues in dermatology: informed consent, complications and medical malpractice. AB - Legal considerations can arise in almost any aspect of a dermatology practice. A full textbook on health care law would be required to adequately cover the varied legal issues as they relate to dermatology. This article will focus on the relationship between informed consent and the development of complications that may lead to a cause of action based on negligence. Because it is the lack of informed consent that may form the basis of a medical malpractice claim, the issues of what constitutes a medical malpractice claim will be fully described. PMID- 17349557 TI - Complications and adverse reactions in the use of newer biologic agents. AB - New developments in genetic engineering and biotechnology have allowed the creation of bioengineered molecules that target specific steps in the pathogenesis of several immune-mediated disorders, including Crohn's disease, rheumatoid arthritis, psoriasis and psoriatic arthritis, ankylosing spondylitis, pemphigus, and B-cell lymphoma. These drugs work by eliminating pathogenic T cells (alefacept), blocking T-cell activation and/or inhibiting the trafficking of T cells (efalizumab), changing the immune profile from Th1 to Th2, blocking cytokines (eg, tumor necrosis factor alpha antagonists including etanercept, infliximab and adalimumab, or interleukin-1-receptor antagonists [anakinra]), or eliminating pathogenic B cells (rituximab). This article reviews the complications and adverse reactions associated with these medications. PMID- 17349558 TI - Adverse events associated with nonablative cutaneous laser, radiofrequency, and light-based devices. AB - Medical and esthetic indications and demand for nonablative laser and light-based treatments are increasing. Although these are generally safe procedures, laser practitioners should be aware of potential complications that may be associated with therapy. An adverse event may be defined as any undesirable effect, even if expected, that occurs with laser treatment. These adverse events can be related to patient factors, professional errors, common side effects, and more serious complications. A variety of providers, including nondermatologists, perform laser treatments and must be aware of therapeutic outcomes as well as potential complications after laser surgery. Clinical indications for nonablative laser treatments, common side effects, and more serious adverse events will be reviewed in addition to treatment and prevention of these potential complications. PMID- 17349559 TI - Complications of sclerotherapy. AB - Sclerotherapy is the systematic, targeted elimination of intracutaneous and subcutaneous varicose, reticular, telangiectasias by the injection of a locally irritating chemical substance, called a sclerosant. The endpoint of this process is functionally analogous to surgical removal of a vein. However, regardless of the best of intentions, complications can and will occur with enough sclerotherapy treatments. Complications resulting from sclerotherapy can be divided into the following categories for ease of explanation: (1) frequent but transient, (2) rare but self-limited, and (3) rare but major. This article will focus on select complications in sclerotherapy, review the most common complications observed, and discuss how to minimize these in daily practice. PMID- 17349560 TI - Complications with the use of botulinum toxin type A for cosmetic applications and hyperhidrosis. AB - In dermatology, botulinum toxin is now most often used to reduce dynamic facial creases and treat primary focal hyperhidrosis. The exemplary safety record of this medication is such that after nearly 2 decades, it is not known to have any long-term adverse events. Transient adverse events, such as mild injection pain, are typically minor and spontaneously remitting. Headache, nausea and flu-like symptoms, lid and brow ptosis after upper face injection, lower face asymmetry after perioral injection, and fine motor impairment after palmar injection are uncommon to rare. Understanding of anatomic landmarks and site-specific precautions can further mitigate the incidence of unwanted effects. Patients who do experience uncommon, transient effects can be reassured that these are not dangerous and will resolve completely without intervention. PMID- 17349561 TI - Adverse effects when injecting facial fillers. AB - Facial soft-tissue augmentation has become ubiquitous in cosmetic dermatology. In the appropriate patient and with appropriate training, fillers can temporarily eliminate rhytides, creases, and defects, thereby producing a rejuvenated appearance. Yet, even in the most experienced injectors, there can be complications. These adverse effects can be divided into early and late and range from bruising to necrosis. Understanding the anatomy, limitations of the filler and proper technique can reduce the risk of adverse effects. When a complication occurs, the practitioner should understand how to manage them from observation to surgical intervention. PMID- 17349562 TI - Bleeding complications in dermatologic surgery. AB - Although the overall incidence is low, bleeding complications in dermatologic surgery can occur and be the source of significant patient morbidity. In this article, we summarize the key aspects of preoperative assessment of patients at risk for bleeding. A review of current issues and literature regarding safe continuation of anticoagulant and antiplatelet medications in dermatologic surgery patients is also presented. In addition, principles for management of bleeding events, should they occur, are also highlighted. PMID- 17349563 TI - Infectious complications and antibiotic use in dermatologic surgery. AB - Infection rates in dermatologic surgery are low, ranging on average from 1 to 3%. Studies have shown that many practitioners likely overuse antibiotics, both for prevention of wound infection and in endocarditis prophylaxis. This article discusses patient and environmental risk factors in would infection. Data on wound infection prophylaxis are reviewed, and specific guidelines set forth with regards to appropriate antibiotic usage, drug selection, dosage, and timing. In addition, recommendations surrounding endocarditis and prosthetic joint infection prophylaxis are presented as they apply to dermatologic surgery. PMID- 17349564 TI - Pediatric surgical pearls: minimizing complications. AB - Performing dermatologic surgery in infants and children presents unique challenges. A thorough understanding of both pediatric developmental milestones and their unique surgical circumstances is essential to providing optimal dermatologic care of the pediatric patient. In this work, we combine the authors' experiences with data from the literature to provide pediatric dermatologic procedural pearls. PMID- 17349565 TI - Giant cell fibroblastoma: an update and addition of 86 new cases from the Armed Forces Institute of Pathology, in honor of Dr. Franz M. Enzinger. AB - A quarter of a century ago at the International Academy of Pathology in Boston, Mass, Drs Enzinger and Shmookler's seminal abstract on giant cell fibroblastoma (GCF) included 20 GCFs on the back and thigh of mostly male children. These tumors involved dermis and subcutis, and had parallel fascicles of wavy uniform spindled cells with wiry collagen, dense sclerosis, and gaping spaces with scattered and rimming pleomorphic giant cells. EM suggested fibroblastic phenotype. All cases had benign behavior, but almost half recurred. The caveat was mistaking this tumor for a malignancy. In 1989, Drs Enzinger, Shmookler, and Weiss published this abstract as 28 cases from the AFIP (1960-1981), including 4 adults up to 55 years old. They proposed a relationship of this childhood tumor to dermatofibrosarcoma protuberans (DFSP). Since these original descriptions of GCF, there has been additional immunohistochemical and molecular support for a relationship between DFSP and GCF. We reviewed additional AFIP cases of GCF since 1981, in honor of Dr Enzinger. These new cases included 60 males and 26 females, whose ages ranged from 6 months to 62 years (median, 6 years; 62%, younger than 10 years; 77%, younger than 20 years; and only 10 patients were older than 40 years). Thirty-nine GCF cases with evaluable epidermis were observed to be protuberant, one with superficial ulceration. Most cases were dermal and subcutaneous, 3 purely dermal, and 5 involved superficial skeletal muscle. Almost all cases demonstrated a honeycomb pattern, and several, a parallel pattern of infiltration. Several cases spared adnexa. Pure GCF areas ranged from solid and collagenized to angiectoid and myxoid, the latter with small to large cystlike spaces. Most cases were relatively hypocellular, except one case with more atypia and mitotic activity. GCF demonstrated myoid whorls in 2 cases, a feature previously described in DFSP. Most remarkable is the peculiar perivascular lymphocytes in an onionskin pattern in GCF, not observed in DFSP. Furthermore, histologic intralesional hemorrhage seems to be common in GCF, particularly near the fascia. Fourteen of our 86 cases demonstrated 5% to 70% (median, 20%) dense nongiant cell storiform areas, interpreted as hybrid GCF-DFSP. Three of these cases demonstrated hypercellular DFSP. One hybrid case had fibrosarcomatous transformation. Two cases of pure GCF recurred as a hybrid tumor with DFSP areas, one of these with hypercellular DFSP. In all but one case, the DFSP was adjacent to GCF with an abrupt transition. Most cases studied were positive for CD34 (more intense in DFSP than relatively hypocellular GCF areas) and negative for smooth muscle actin, desmin, HMB-45, keratin, and S100 protein. GCF is exactly clinically and morphologically the same as Dr Enzinger and colleagues originally described it. Additional observations of marked perivascular and onionskin-like chronic inflammation and consistent hemorrhage may aid in the diagnosis of this previously well-described tumor. Collectively, we now have even more convincing morphologic, immunophenotypic, and molecular evidence that GCF is on a spectrum with DFSP. PMID- 17349566 TI - Changing trends in the distribution of the histologic types of lung cancer: a review of 4,439 cases. AB - Lung cancer is the second most common cancer and the leading cause of cancer death in both men and women. The purpose of the study is to explore the distribution of the 4 major histologic types of lung carcinoma and the incidence of lung cancer with reference to all other sites of cancer. The clinical and histopathologic data of 4,439 patients with lung carcinoma between January 1980 and December 2003 were reviewed. Adenocarcinoma has become the most frequent histologic type in men and women (36.8% and 46.5%, respectively), followed by squamous cell carcinoma (31.6% and 25.4%, respectively). The incidence of large cell (undifferentiated) carcinoma in men and women is 18.0% and 9.9%, respectively. The incidence of small cell carcinoma in men and women is 13.7% and 18.3%, respectively. In addition, analysis of our data indicates that lung cancer rate is decreasing, relative to all other primary cancer sites. The results of this study suggest that the incidence of lung cancer has decreased in comparison with other sources of cancer in southern Texas. This observation is consistent with the current national trends. In addition, there are significant changes in the distribution of the major histologic types of lung cancer. The results of this study may portend important changes in the selection of targeted therapy and patient management. PMID- 17349567 TI - Unusual findings in papillary thyroid microcarcinoma suggesting partial regression: a study of two cases. AB - Histologic changes of regression have been recognized in many malignant tumors, although they have not been documented in thyroid carcinoma. We analyze here the histologic features of 2 cases of papillary thyroid microcarcinoma, one of the diffuse sclerosing variant and another multicentric of the follicular variant, that suggest partial regression. The histologic and clinical features of the 2 thyroid microcarcinomas were compared with the features of regression reported in other tumors. Hematoxylin and eosin stains were examined in each case. In addition, immunoperoxidase stains for thyroglobulin and thyroid transcription factor-1 were performed on the metastatic and primary lesions of each case. Immunostains for CD4 and CD8 performed on the thyroid lesions were also examined. Both patients presented with metastatic papillary thyroid carcinoma in regional lymph nodes with no clinical or radiologic evidence of primary tumor in the thyroid glands. When examined, the thyroid glands revealed only microscopic foci of papillary thyroid carcinoma measuring less than 1.5 mm, diffuse sclerosis and a lymphocytic infiltrate mainly composed of cytotoxic T lymphocytes around the neoplastic microfollicles. Numerous psammoma bodies were also found in the thyroid of case 1, and venulitis similar to that seen in acute hepatic rejection was also seen in the microcarcinoma of case 2. The 2 patients reported had papillary thyroid microcarcinomas measuring less than 1.5 mm and features suggestive of regression characterized by extensive fibrosis, an accompanying T lymphocyte infiltrate, venulitis, and only a few clusters of neoplastic cells or a few neoplastic follicles. Thus, we believe that these histologic changes suggest regression because papillary thyroid microcarcinomas measuring less than 1.5 mm do not metastasize and have been considered innocuous or medical curiosities. PMID- 17349568 TI - Immunohistochemical expression of PTEN and beta-catenin for endometrial intraepithelial neoplasia in Japanese women. AB - PTEN and beta-catenin are the most common genes for which genetic abnormalities are found in endometrioid adenocarcinoma (type I) and even in their precursors. Currently, the World Health Organization (WHO) classifies endometrial hyperplasia as a premalignant disease. However, one of the problems in the current WHO endometrial hyperplasia schema is that it is not always a reproducible classification system. Subsequently, the alternative molecular genetics and morphometric-based classification, referred to as the endometrial intraepithelial neoplasia (EIN) classification system, has been proposed. We reclassified endometrial lesions in Japanese women using the EIN category and compared them with the results of PTEN as well as beta-catenin immunohistochemistry. A total of 117 cases that were initially diagnosed as endometrial hyperplasia according to WHO classification were reevaluated histopathologically by the EIN diagnosis category. They were classified into 38 EIN and 32 benign architectural changes of unopposed estrogen (BAC), and 47 cases were excluded. In addition, for comparison, we examined 20 cases of normal proliferative endometrium (NPE). Subsequently, the expressions of PTEN and beta-catenin were analyzed immunohistochemically. Glandular epithelium was positive for PTEN in all the cases of NPE (20/20), whereas 12.5% (4/32) of BAC and 34.2% (13/38) of EIN were PTEN-null (negative). Endometrial intraepithelial neoplasia was significantly less frequently positive for PTEN than NPE (P < .025). The nuclear staining for beta-catenin was seen in 26.3% (10/38) of EIN cases, and the intensity was generally strong. Instead, none of the BAC or NPE showed positive nuclear staining. Thus, the nuclear staining was statistically more frequently seen in EIN than in the other 2 categories (P < .025 for each). In addition, 22 of 38 EIN cases (57.9%) were either PTEN-negative or nuclear beta-catenin-positive. This combination was statistically significantly more frequently seen than BAC (4/32, 12.5%) (P < .001) and NPE (0/20, 0%) (P < .0001). Immunohistochemical loss of PTEN and positive nuclear staining of beta-catenin were frequently seen in EIN but were not seen in NPE cases in Japanese women. The combination of PTEN negative/beta-catenin-positive results may become the reliable marker for detecting EIN. PMID- 17349569 TI - Granulomatous lobular mastitis: two case reports with focus on radiologic and histopathologic features. AB - Granulomatous lobular mastitis (GLM) is a rare, benign condition with an unknown etiology that can appear as cancer on mammogram, ultrasound, and magnetic resonance imaging. The terminology of GLM was first named by Going et al (J Clin Pathol 1987;40:535-540) in 1987 after he noted the lobule centered distribution on histologic exam. We present 2 case reports of GLM that clinically and radiographically appeared as malignant lesions. The first case was a 31-year-old woman with a 1-month history of breast mass, and the second case was a 33-year old woman with a 2-week history of breast mass. Both cases were histologically diagnosed as GLM. Retrospectively, we identified ultrasound and magnetic resonance imaging characteristics that may be used in the future to classify the breast mass before biopsy. PMID- 17349570 TI - Carcinoid tumor of the gall bladder. AB - Carcinoid of the gall bladder and bile duct is a rare tumor. Primary gall bladder and biliary duct system carcinoids constitute less than 1% of all carcinoid tumors arising from different parts of the body. We describe a case of carcinoid tumor of the gall bladder in a 53-year-old woman. The rarity of this entity prompted us to present our patient as a case report. There have been only 33 cases described in the literature. PMID- 17349571 TI - Xanthogranulomatous salpingitis associated with fallopian tube mucosal endometriosis: a clue to the pathogenesis. AB - Xanthogranulomatous salpingitis is an unusual inflammatory lesion of the fallopian tube, characterized by accumulation of foamy macrophages in the wall of the fallopian tube along with other chronic inflammatory cells. Only a few cases of xanthogranulomatous salpingitis have been reported in the English medical literature, some under different nomenclature. An association, most commonly with pelvic inflammatory disease and endometriosis, has been suggested. A 41-year-old woman with prior history of breast carcinoma underwent bilateral salpingoophorectomy because of hematosalpinx. The histology revealed xanthogranulomatous salpingitis in the setting of extensive fallopian tube mucosal endometriosis, endometritis, and presence of an intrauterine contraceptive device. Multiple etiologies have been linked to the xanthogranulomatous process at this location in previously reported cases. A whole spectrum of changes may exist in this lesion and probably represent a specialized form of tissue reaction secondary to multiple etiologies. Although it has been associated with pelvic endometriosis, it has never been demonstrated through progressive changes, beginning with mucosal endometriosis to the full blown xanthogranulomatous inflammation. To the best of our knowledge, this is the first reported case that demonstrates different stages in the pathogenesis of this lesion and provides an insight into the histogenesis of this entity. PMID- 17349572 TI - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. AB - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is an extremely rare pulmonary lesion, with only 39 cases reported in the literature. We report an additional case and review the literature. The patient is a 41-year-old man with a 5-year history of progressive dyspnea, cough, and wheezing. He was initially diagnosed as having bronchial asthma but did not respond to treatment of bronchodilators and inhaled steroids. Pulmonary function tests showed airflow obstruction. Chest computed tomography revealed a mosaic pattern of air trapping and thickening of bronchial walls. Open lung biopsy showed diffuse proliferation of pulmonary neuroendocrine cells within the bronchiolar epithelium, often bulging into or obliterating the bronchiolar lumen. These cells also breached the basement membrane, forming tumorlets. There was prominent peribronchiolar fibrosis and obliterative bronchiolitis. The pathologic evaluation of lung tissue is currently the gold standard in making a definitive diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, and all the reported cases were diagnosed by either open lung biopsy or lobectomy. PMID- 17349573 TI - A case of primary unilateral adrenal Burkitt-like large cell lymphoma presenting as adrenal insufficiency. AB - Primary adrenal lymphoma is extraordinarily rare, in comparison with secondary adrenal involvement by non-Hodgkin lymphoma. Although higher-resolution imaging techniques have enhanced detection of adrenal masses, biopsy or excision is often needed for definitive diagnosis. Percutaneous computed tomography-guided fine needle aspiration has great diagnostic value in the workup of adrenal masses, but is limited by sampling error and artifacts. Primary adrenal lymphoma most commonly manifests with diffuse large B-cell morphology. Burkitt-like large cell lymphoma morphology has been previously reported only once, to our knowledge. We report an 80-year-old man presenting with unilateral primary adrenal lymphoma showing Burkitt-like morphology and adrenal insufficiency. Fine needle aspiration yielded a dispersed population of monomorphic, medium to large cells suggestive of lymphoma. Although dispersed cell populations cytologically favor lymphoma, metastatic poorly differentiated carcinoma and adrenal cortical carcinoma can manifest similarly. Integrated histological, immunohistochemical, and flow cytometric immunophenotyping would provide an accurate and definitive diagnosis. We review the literature and discuss important issues with regard to diagnosis. PMID- 17349574 TI - Concurrent angiomyolipoma and two oncocytomas in the same kidney. AB - We report on a rare case of synchronous angiomyolipoma (AML) and 2 oncocytomas (OCs) in the same kidney of a 73-year-old woman. During the course of a follow-up for a long-standing staghorn calculus in the left kidney, a 4-cm right suprarenal mass and a small solid nodule adjacent to a cyst in the midportion of the right kidney were radiographically discovered. A radical nephrectomy was performed. The suprarenal tumor was found to be an AML, and the small nodule was an OC (1.5 cm). An additional OC (0.8 cm) elsewhere in the right kidney was also identified. The coexistence of AML and other renal tumors is uncommon. Among reported cases, conventional renal cell carcinoma, possibly reflecting its higher incidence, has been the most common concurrent tumor with AML. Although only rare cases of simultaneous AML and OC have been reported in the literature, it appears that the proportion of OC among concurrent renal tumors with AML is higher than expected based on its frequency among all surgically resected renal neoplasms. Whether there is a pathogenetic association between AML and OC needs to be further investigated. PMID- 17349575 TI - Histology: a unique area of the medical laboratory. AB - Fundamental differences in samples, procedures, nature of results, automation, productivity, staffing levels, and background decision making along work flow and turnaround times characterize histology as a unique area within the medical laboratory. For histology laboratories to function successfully, individual and collective training, well-defined goals, and implemented accountabilities with effective supervision are required. The pathologist, as immediate client of the histology laboratory, has to be involved in the whole operation to assure optimal patient care. PMID- 17349576 TI - The cause of sarcoidosis: the Centurial enigma solved. AB - I am an experienced pathologist (4 decades), and I can now confidently perceive the cause of sarcoidosis. I can see clearly now because of 2 things: (1) modern evidence indicating a genetic-based immune dysregulation as an essential predisposing causal cofactor and (2) a century of accumulated pathology observations relevant to the point. The first factor helps explain numerous environmental, clinical, and research uncertainties, contradictions, and puzzles. The second factor, not readily available to clinicians, allows me to perceive the answer. The argument: (1) although most pathologists are vague in their conception of a "granuloma," the discerning pathologist realizes that a "true," well-formed epithelioid granuloma has only a very limited number of possible causes; (2) these causes do not include autoimmune diseases nor "self perpetuating" granulomas to a "cleared" infectious agent; (3) the only feasible 2 causes are an infection or a reaction to a foreign particulate; (4) the only possible infections are ones where the infectious agent can be seen under the microscope; (5) experienced infectious disease pathologists do not see a microorganism (after a century of looking); (6) foreign particulates are therefore the cause (the only feasible cause remaining). This is not a new speculation; what I contribute that is new are pathology perceptions that confirm it beyond speculation. The reason the particles are not seen microscopically is that they are nanoparticles (less than a micrometer in largest dimension); larger particles are cleared from the lung efficiently by mucociliary transport. Direct evidence for this nanoparticulate theory is abundant. A recent case I studied has some compelling details. The nanoparticle theory should be accepted and acted upon, guiding further research, and there are risk-free measures that probably could benefit patients now. PMID- 17349577 TI - The EGF receptor Hokey-Cokey. AB - In cancer, the epidermal growth factor (EGF) receptor (EGFR) can be activated by mutations that disrupt the inactive conformation and allow the active conformation to predominate. Structural studies have elucidated the molecular events that lead to EGFR activation and shown that small-molecule anti-EGFR drugs can bind to either the inactive or the active conformation of the kinase domain. In this issue of Cancer Cell, Yun et al. present 12 crystal structures of the wild-type or mutant forms of the EGFR kinase domain bound to four different ligands. This study will prove invaluable to those developing novel anti-EGFR drugs. PMID- 17349578 TI - A case of mistaken identity? Nonductal origins of pancreatic "ductal" cancers. AB - In this issue of Cancer Cell, Guerra and colleagues provide important new insights regarding the ability of specific pancreatic cell types to generate invasive pancreatic cancer. First, they demonstrate that classical pancreatic "ductal" neoplasia can be induced by activation of oncogenic Kras in nonductal exocrine cells. Second, they show that, while Kras activation in immature acinar and centroacinar cells is readily able to induce ductal neoplasia, Kras-mediated tumorigenesis in mature exocrine pancreas requires the induction of chronic epithelial injury. The results shed new light on the "cell of origin" of pancreatic ductal cancer and demonstrate that chronic pancreatitis provides a permissive environment for Kras-induced pancreatic neoplasia. PMID- 17349579 TI - A brake becomes an accelerator: PTP1B--a new therapeutic target for breast cancer. AB - The protein tyrosine phosphatase PTP1B, previously recognized for its role in downregulating insulin and leptin signaling, has now been shown to function as a positive regulator of signaling events associated with breast tumorigenesis. Inhibitors of PTP1B that have been developed as drug candidates for treatment of diabetes and obesity may offer new avenues for the treatment of breast cancer. PMID- 17349580 TI - Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. AB - Mutations in the EGFR kinase are a cause of non-small-cell lung cancer. To understand their mechanism of activation and effects on drug binding, we studied the kinetics of the L858R and G719S mutants and determined their crystal structures with inhibitors including gefitinib, AEE788, and a staurosporine. We find that the mutations activate the kinase by disrupting autoinhibitory interactions, and that they accelerate catalysis as much as 50-fold in vitro. Structures of inhibitors in complex with both wild-type and mutant kinases reveal similar binding modes for gefitinib and AEE788, but a marked rotation of the staurosporine in the G719S mutant. Strikingly, direct binding measurements show that gefitinib binds 20-fold more tightly to the L858R mutant than to the wild type enzyme. PMID- 17349581 TI - Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. AB - Oncogenic Kras initiates pancreatic tumorigenesis, while subsequent genetic events shape the resultant disease. We show here that concomitant expression of Kras(G12D) and haploinsufficiency of the Smad4/Dpc4 tumor suppressor gene engenders a distinct class of pancreatic tumors, mucinous cystic neoplasms (MCNs), which culminate in invasive ductal adenocarcinomas. Disease evolves along a progression scheme analogous to, but distinct from, the classical PanIN-to ductal adenocarcinoma sequence, and also portends a markedly different prognosis. Progression of MCNs is accompanied by LOH of Dpc4 and mutation of either p53 or p16. Thus, these distinct phenotypic routes to invasive adenocarcinoma nevertheless share the same overall mutational spectra. Our findings suggest that the sequence, as well as the context, in which these critical mutations are acquired helps determine the ensuing pathology. PMID- 17349582 TI - In vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: a cell and animal model of virally induced Kaposi's sarcoma. AB - Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial-lineage cells generates a cell (mECK36) that forms KS-like tumors in mice. mECK36 expressed most KSHV genes and were angiogenic, but they didn't form colonies in soft agar. In nude mice, mECK36 formed KSHV-harboring vascularized spindle cell sarcomas that were LANA+/podoplanin+, overexpressed VEGF and Angiopoietin ligands and receptors, and displayed KSHV and host transcriptomes reminiscent of KS. mECK36 that lost the KSHV episome reverted to nontumorigenicity. siRNA suppression of KSHV vGPCR, an angiogenic gene upregulated in mECK36 tumors, inhibited angiogenicity and tumorigenicity. These results show that KSHV malignancy is in vivo growth restricted and reversible, defining mECK36 as a biologically sensitive animal model of KSHV-dependent KS. PMID- 17349583 TI - Molecular definition of breast tumor heterogeneity. AB - Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-beta pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations. PMID- 17349585 TI - Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. AB - Pancreatic ductal adenocarcinoma (PDA), one of the deadliest human cancers, often involves somatic activation of K-Ras oncogenes. We report that selective expression of an endogenous K-Ras(G12V) oncogene in embryonic cells of acinar/centroacinar lineage results in pancreatic intraepithelial neoplasias (PanINs) and invasive PDA, suggesting that PDA originates by differentiation of acinar/centroacinar cells or their precursors into ductal-like cells. Surprisingly, adult mice become refractory to K-Ras(G12V)-induced PanINs and PDA. However, if these mice are challenged with a mild form of chronic pancreatitis, they develop the full spectrum of PanINs and invasive PDA. These observations suggest that, during adulthood, PDA stems from a combination of genetic (e.g., somatic K-Ras mutations) and nongenetic (e.g., tissue damage) events. PMID- 17349586 TI - Long-term functional results of primary reconstruction of severe forearm injuries. AB - Severe forearm injuries caused by machinery such as a power saw represented about 0.2% of all upper limb injuries operated on in the plastic surgery section of our institute between 1993 and 1997. These are complex and contaminated injuries with severe damage to skin, muscles, tendons, nerves, vessels and bones. Primary repair or reconstruction of all the divided vital structures was carried out in our series of four patients, including one 4-cm cable nerve graft for a median nerve defect. After an average 22-month follow up, the functional results showed grade M4 motor recovery and better than grade S3+ sensory recovery of the hand in all four patients. We suggest that a definitive primary procedure is best when possible. This will achieve a better functional outcome from early neural regeneration, and will reduce the frequency of secondary procedures, cause less scarring, and shorten the duration of hospital stays and rehabilitation periods. PMID- 17349584 TI - Fez1/Lzts1 absence impairs Cdk1/Cdc25C interaction during mitosis and predisposes mice to cancer development. AB - The FEZ1/LZTS1 (LZTS1) protein is frequently downregulated in human cancers of different histotypes. LZTS1 is expressed in normal tissues, and its introduction in cancer cells inhibits cell growth and suppresses tumorigenicity, owing to an accumulation of cells in G2/M. Here, we define its role in cell cycle regulation and tumor progression by generating Lzts1 knockout mice. In Lzts1(-/-) mouse embryo fibroblasts (MEFs), Cdc25C degradation was increased during M phase, resulting in decreased Cdk1 activity. As a consequence, Lzts1(-/-) MEFs showed accelerated mitotic progression, resistance to taxol- and nocodazole-induced M phase arrest, and improper chromosome segregation. Accordingly, Lzts1 deficiency was associated with an increased incidence of both spontaneous and carcinogen induced cancers in mice. PMID- 17349587 TI - Extended reverse dorsal metacarpal artery flap: clinical experience and donor site morbidity. AB - Extended reverse dorsal metacarpal artery (RDMA) flaps use the skin from the dorsum of the hand to cover defects of the long fingers up to the distal phalanx. The authors present a series of 12 patients who underwent closure of defects of the long fingers with these flaps. As relevant literature is scarce, special emphasis was put on donor site morbidity. Active and passive total range of motion (TRM) and pinch grip strength of the finger neighbouring the reconstructed one were evaluated and compared to the corresponding finger of the contralateral hand. The donor site was furthermore evaluated for cosmetic appearance and pain. There was no statistically significant difference for active and passive TRM. The difference for pinch grip reached statistical significance (p=0.04). Subjective evaluation of pain and cosmetic appearance by the patients revealed a mean pain value of 1.25 on a visual analogue scale (0=no pain, 10=maximal imaginable pain) and a mean estimation of cosmetic appearance of 8 (visual analogue scale, 0=worst cosmetic result, 10=best cosmetic result). In conclusion, compared to other flaps, the extended RDMA flap is a fast, secure and single-stage procedure for defect coverage on the long fingers with low donor site morbidity. PMID- 17349588 TI - Evaluation of moving and static two point discriminations of volar forearm skin before and after transfer as a sensate radial forearm island flap in reconstruction of degloving injury of the thumb. AB - In degloving injury of the thumb the large skin defect needs cover with sensate, glabrous and pliable skin. Although coverage of this defect with a sensate free flap from the foot is the best choice, most commonly, cover is achieved using a non-sensate distant pedicle flap. Between 2001 and 2003, degloving injuries of the thumb in eight patients were reconstructed using a sensate radial forearm flap in the sensory territory of the lateral ante-brachial nerve of the forearm which was repaired to the digital nerve of the thumb (six cases) or to a branch of the sensory radial nerve (two cases). Follow-up period ranged from 17 to 41 months (mean: 29.9 months). Sensory evaluation was performed using the moving two point discrimination (M-2PD) and static two point discrimination (S-2PD) of the volar forearm skin. These altered significantly after transfer and their values approached those of the contra-lateral thumb but never reached normal sensation (p<0.01). Sensate radial forearm island flap is a reliable option to cover a large defect of the thumb such as degloving injury and the sensation produced is acceptable. PMID- 17349589 TI - Surgical treatment and results in 17 cases of open lacerations of the extensor hallucis longus tendon. AB - There is a scarcity of information on extensor hallucis longus tendon injuries and published studies frequently offer conflicting treatment recommendations and results. PATIENTS AND METHODS: This paper reports on the treatment and results of open lacerations of the extensor hallucis longus tendon in 17 patients treated by a plastic surgeon over a period of 12 years. All injuries occurred due to industrial accidents. All patients were males with a mean age of 30 years (range=21-49 years). All zones of tendon injury were represented except zones 2 and 5. Sixteen patients underwent surgical exploration within 24h of injury and one patient had a delayed repair using a tendon graft. The laceration of the tendon was complete in 15 patients, and in these patients, the tendon repair was protected for 6 weeks using k-wires to the big toe and short-leg walking cast. The remaining two patients had partial tendon lacerations and were treated conservatively (without tendon suturing) and immediate unrestricted mobilisation. One patient had significant soft tissue loss requiring reverse sural artery flap cover. At final follow-up (mean=3 months), the results of tendon repair were assessed as per the grading system of Lipscomb and Kelly, and the AOFAS hallux score for pain (maximum score of 40 points indicating no pain) and for functional capability (maximum score of 45 points). RESULTS: All patients healed with no infections or painful neuromas. Two patients experienced prolonged mild aching pain in the foot on walking, but the pain eventually resolved in both patients. All patients returned back to work 2.5-5 months after surgery. As per Lipscomb and Kelly's grading system, the result was graded as good in four patients and fair in the remaining 13 patients. No poor results were seen. The AOFAS hallux pain score was 40 points in all patients and the mean functional capability score was 42.1 points (range=40-45 points). CONCLUSION: A large series of extensor hallucis longus tendon lacerations is reported. Treatment and the methods of immobilisation are given for various zone and injury types. Although it is difficult to obtain a completely normal range of motion of the big toe after surgery, all patients are expected to recover good active extension and return back to work pain-free. PMID- 17349590 TI - Nomenclature for fingers and phalanges: to name or to number? AB - INTRODUCTION: Two systems exist for describing fingers and phalanges: Naming and Numbering. This can cause confusion for clinicians. We compared the two systems to see if one was better understood. METHODS: Thirty-eight clinicians were asked a questionnaire to identify 11 terms on hand outline drawings. RESULTS: Naming was better understood than Numbering both overall (McNemar's test, p=0.000026) and with just abbreviations (p=0.0017) or full terms (p=0.000074). Radial/ulnar was superior to medial/lateral for laterality (p=0.046). Within the Naming system, the full terms were less ambiguous than abbreviations (p=0.000012). Our study suggests that Naming is better understood than Numbering and that full terms are preferable to abbreviations. To describe laterality, radial and ulnar are less ambiguous that medial and lateral. PMID- 17349591 TI - Choice of flap for the management of deep sternal wound infection--an anatomical classification. AB - BACKGROUND: Infection of a median sternotomy wound is a rare albeit potentially fatal complication because of the risk of mediastinitis and deep sternal wound infection. Current treatment of deep sternal wound infection comprises antibiotics, debridement and transposition of muscle or omental flaps to fill the anterior mediastinal dead space. METHODS: A retrospective analysis of the deep sternal wound infections treated in our unit over a nine-year period was performed. RESULTS: Out of the 11 903 consecutive coronary artery bypass graft procedures performed, 27 patients were referred to plastic surgery for management of deep sternal wound infection with flaps. Wounds were classified based on their location on the sternum as type A (upper (1/2)), B (lower (1/2)) or C (whole of sternum). Five patients had type A wounds, 12 type B wounds and 10 type C wounds. The mean age was 68 years and the M:F ratio was 20:7. We describe guidelines for the choice of flap for sternal wound reconstruction, according to the anatomical site of the wound dehiscence. PMID- 17349592 TI - Antibiotic use in abdominoplasty: prospective analysis of 207 cases. AB - The increasing demand for plastic surgery of the abdomen has also increased the number of complications, some of them very difficult to manage. It has been stated that antibiotics are unquestionably effective in preventing postoperative wound infections. In the present study, we aimed to provide guidelines for the use of prophylactic antibiotics in abdominoplasty operations. A prospective study was planned on 207 patients. Three study groups were formed according to the administration of antibiotics as follows: group 1, no antibiotics; group 2, preoperative antibiotics only; and group 3, both preoperative and postoperative antibiotics. Twenty patients showed bacterial growth in the intraoperative bacterial culture. There was significant difference in the incidence of infection between groups 1 and 2, groups 1 and 3, but there was no difference between groups 2 and 3. In conclusion, we recommend a single preoperative dose of intravenous antibiotic to prevent infection and also secure the patient from antibiotic side effects. PMID- 17349593 TI - An alternative classification of incisional hernias enlisting morphology, body type and risk factors in the assessment of prognosis and tailoring of surgical technique. AB - Incisional hernias occur in 5-10% of patients who have undergone laparotomy and are associated with a high morbidity and significant socioeconomic costs. Better understanding of the anatomy and improved methods for reinforcement of the abdominal wall with alloplastic meshes have reduced the recurrence rate to 1-10% depending on the type of hernia and the technique employed. A number of surgical repair techniques and mesh types are available. However, precise criteria for incorporating patient body type, risk factors for recurrence, hernia morphology, and the available biomaterials into planning of the surgical approach (open versus laparoscopic) have yet to be established. The elaboration of such criteria would require comparative evaluation of long-term results in a sufficiently large number of patients, e.g. in multicentre trials or meta-analyses of standardised data from different centres. Current classifications have the drawback that they fail to take account of prognostically relevant risk factors for recurrence and are not self-explanatory. The authors present a classification of incisional hernias that is self-explanatory and practicable in routine clinical practice. Based on the cornerstones of morphology (M), hernia size in cm (S), and risk factors for recurrence (RF), the scheme enables easy description and documentation of the hernia, and provides evidence for the indications and limitations of the main surgical repair techniques. Since randomised studies can scarcely be conducted on incisional hernias due to the numerous morphological variables, the classification presented here may offer an alternative means for comparative data analysis. PMID- 17349594 TI - Inverting bilateral figure-of-eight suture of the rectus sheath after burst abdomen with destruction of the linea alba: a new technique. AB - The authors report a new technique for secondary abdominal closure after burst abdomen as illustrated by the case of a patient who developed a perforated sigmoid diverticulitis following septic polyarthritis. Sigmoid resection was followed on the sixth day postoperative by a burst abdomen. Upon abdominal revision the burst abdomen was found to be caused by necrotic destruction of the linea alba. Abdominal wall closure was achieved using the novel technique of inverting bilateral interrupted figure-of-eight suture of the anterior and posterior rectus sheaths in combination with relieving lateral incisions and mesh implantation in the sublay technique. It remains for future studies to show whether this technique can reduce the high incisional hernia rate following secondary abdominal wall closure. PMID- 17349595 TI - The dynamic rotation of Langer's lines on facial expression. AB - Karl Langer investigated directional variations in the mechanical and physical properties of skin [Gibson T. Editorial. Karl Langer (1819-1887) and his lines. Br J Plast Surg 1978;31:1-2]. He produced a series of diagrams depicting lines of cleavage in the skin [Langer K. On the anatomy and physiology of the skin I. The cleavability of the cutis. Br J Plast Surg 1978;31:3-8] and showed that the orientation of these lines coincided with the dominant axis of mechanical tension in the skin [Langer K. On the anatomy and physiology of the skin II. Skin tension. Br J Plast Surg 1978;31:93-106]. Previously these lines have been considered as a static feature. We set out to determine whether Langer's lines have a dynamic element and to define any rotation of the orientation of Langer's lines on the face with facial movement. One hundred and seventy-five naevi were excised from the face and neck of 72 volunteers using circular dermal punch biopsies. Prior to surgery a vertical line was marked on the skin through the centre of each naevus. After excision distortions of the resulting wounds were observed. The orientation of the long axis of each wound, in relation to the previously marked vertical line, was measured with a goniometer with the volunteer at rest and holding their face in five standardised facial expressions: mouth open, smiling, eyes tightly shut, frowning and eyebrows raised. The aim was to measure the orientation of the long axis of the wound with the face at rest and subsequent rotation of the wound with facial movement. After excision elliptical distortion was seen in 171 of the 175 wounds at rest. Twenty-nine wounds maintained the same orientation of distortion in all of the facial expressions. In the remaining wounds the long axis of the wound rotated by up to 90 degrees . The amount of rotation varied between sites (p>0.0001). We conclude that Langer's lines are not a static feature but are dynamic with rotation of up to 90 degrees . It is possible that this rotation in the axis of mechanical tension will affect the appearance of the resulting scar. PMID- 17349596 TI - Management of severe tip ptosis in closed rhinoplasty: the horizontal columellar strut. AB - BACKGROUND: Tip ptosis is a relatively common nasal deformity, with an incidence as high as 72% in rhinoplasty patients. Different techniques were described for surgical correction of the droopy tip, such as the lateral crural steel, the lateral crural overlay, the tongue-in-groove technique and others. Most authors agreed that an external rhinoplasty approach is necessary for effectively conducting the alar cartilage-modifying techniques mentioned above. METHODS: In this article we challenge this paradigm and introduce an efficient method for aesthetic correction of severe tip ptosis through an internal rhinoplasty approach. Twenty-three patients with severe ptosis of the nasal tip were operated on by the senior author (MH) between 2000 and 2005 using the described technique. After carrying out the necessary manoeuvres to achieve the desired tip rotation (reduction of cephalic border of alar cartilages, modification of the caudal septum, reduction of upper lateral cartilages), the desired tip position was maintained with the horizontal columellar strut, whose initial operative description appears here. RESULTS: The desired rotation and projection were maintained in all but three patients over the first year after the surgery. In three patients we observed some loss of tip projection after 1 year. We did not witness complications directly related to the horizontal columellar strut. CONCLUSION: The horizontal columellar strut is an efficient tool for stabilising the corrected position of a severely ptotic nasal tip. We recommend adding the horizontal columellar strut to the array of available rhinoplasty techniques. PMID- 17349597 TI - Maxillary growth of adult patients with unoperated cleft: answers to the debates. AB - Maxillary growth of adult patients with unoperated cleft has long been studied, but results varied between different studies. The objectives of this study were to determine the growth potential of adult patients with unoperated clefts compared to the normal population and to differentiate the growth potential among types of clefts. METHODS: Subjects were from the same ethnic group, were more than 16 years of age with non-syndromic cleft and no associated anomalies. The types of cleft included unilateral complete cleft lip and palate (UCLP), bilateral complete cleft lip and palate (BCLP), unilateral cleft lip (UCL) and isolated cleft palate (CP). The sella-nasion-A point (SNA) angle from the cephalometry was measured, and a dental cast study using a three-dimensional imaging system was performed. RESULTS: SNA measurements showed significant differences among different groups, the BCLP group having larger values and the CP group having smaller values when compared with normal values. Dental cast analysis measuring palatal surface area showed a significantly smaller area in patients with cleft as compared to normal controls, but no difference among the different types of cleft. From the linear measurement it was found that the interdental distance was significantly more narrow in the anterior part up to the first premolar region as compared to the control group, especially in the complete cleft groups (UCLP and BCLP). Dentoalveolar arch was also deeper and longer in these complete cleft groups. CONCLUSION: There is an intrinsic tissue deficiency in all groups of patients with cleft; however, the sagittal development is still comparable to that of a normal population. Tissue deficiency mostly occurs in the anterior part. There is no difference in terms of the deficiencies among the different groups of cleft. PMID- 17349598 TI - Cleft palate repair with the use of osmotic expanders: a preliminary report. AB - A new method of cleft palate repair by expansion of tissue by means of osmotic expanders implanted in the first stage of treatment is described. Self-expanding expanders manufactured by OSMED (Ilmenau, Germany) were implanted under the mucoperiosteal layer of the hard palate, on purpose to generate more tissue and provide facility for palate repair performed 24-48h later. Nineteen children aged from 2 to 3 years were operated from January 2004 to 15 April 2005. In clefts<10mm, tissue repair was possible without relaxing incisions. In 11 patients with clefts>10mm, cleft palate repair was more difficult and the outcomes were less favourable. Despite more generous dissection of the neurovascular bundles and other adjunctive measures such as mucosal V-Y plasty [Bardach J, Salyer K. Surgical techniques in cleft lip and palate. Chicago, London: Year Book Medical Publishers, Inc.; 1987.] and suturing of the mucosal grafts at the border of the hard and soft palate, seven 2-4mm fistulae were noted, however. Concluding, in spite of some shortcomings and unacceptable rate of fistula in wide clefts, the above-presented method seems to be an attractive concept. Despite some technical problems related mostly to still tested optimal filling phase, tissue expansion makes palate repair easier, probably without relaxing incisions and bone denudation. Consequently, some adverse effects on facial growth may be reduced. So far, there is no evidence for it, however, and since this is a preliminary report, there is a need for longer observations and larger material. PMID- 17349599 TI - A geometrically sound technique of vermilion repair in unilateral cleft lip. AB - In unilateral cleft lip, there is always a deficiency of vermilion on the medial side of the cleft, which can be augmented by techniques using excess vermilion from the lateral side of the cleft, like the use of a simple V-advancement flap. We developed a modification of Noordhoff's lateral vermilion flap that preserves the parallel relationship of the muco-vermilion line and the white roll but improves results in unilateral cleft lip patients. In a study of 30 patients undergoing surgical repair of complete unilateral cleft lip, we found that this method offers a superior alternative to the straight-line repair. This geometrically sound technique for vermilion reconstruction offers the cleft surgeon a simple and effective method for augmenting total lip height and creating a normal appearing Cupid's bow. PMID- 17349600 TI - Laser hair removal in women with polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS) is one of the most common reasons for women to present seeking removal of facial hair, particularly within the UK National Health Service (NHS). In the NHS, there is geographical variation in the number of laser treatments available to women with PCOS, with some units limiting patients to six treatments whilst others allow unlimited treatments. This study aims to assess the effect of number of treatments on women with PCOS. METHODS: This study prospectively assessed hair counts, hair-free intervals and patient satisfaction in 60 women with PCOS undergoing 3ms pulse duration alexandrite laser treatment. RESULTS: Following six treatments there was a mean 31+/-38% reduction in hair counts (mean+/-SD; P=0.001). Mean hair-free interval (HFI) increased steadily with treatment, from 1.9 weeks after six treatments to 4.3 weeks after 10 treatments (P=0.001). From the postal questionnaire, after an average of 12 treatments, 31% of patients had a HFI longer than 6 weeks compared to only 2.6% after six treatments (P=0.003). Overall, despite the low hair count reductions, 95% of patients were satisfied with treatment. CONCLUSION: In women with PCOS, laser treatment is associated with a poorer than expected reduction in hair counts and HFI following treatment. However, offering more than six treatments does have additional benefits in terms of prolonging HFI and overall patient satisfaction with treatment is very high. PMID- 17349601 TI - Providing pain relief for laser resurfacing: effectiveness of the CoolAnalgesia device. AB - Laser resurfacing is a painful procedure, and is therefore usually carried out under general anaesthetic or local anaesthetic with sedation. However, the small but significant risk of adverse events from either of these methods has resulted in an effort to develop other methods of controlling the pain associated with the use of lasers. This trial describes of the use of a cooling device (the CoolAnalgesia device) with a carbon dioxide laser. The only anaesthetic used was a eutectic mixture of lidocaine anaesthetic (EMLA) applied as a cream to the face at least 60 min prior to the procedure. Twenty consecutive patients attending two laser centres for facial resurfacing were recruited. Each patient was asked to assess the level of pain on a visual analogue scale from 1-10 every 2 min during lasering. Only one of the patients had a mean pain score for the duration of the treatment of above five, four patients recorded a pain score of above five at some stage during their treatment, but none requested that the treatment be stopped. It would appear that the CoolAnalgesia device in combination with EMLA cream provides a level of anaesthesia sufficient to allow laser resurfacing without the use of local anaesthetic injections or intra-venous agents. PMID- 17349602 TI - An analysis of 1361 aesthetic procedures from 2000 to 2005 in a large regional plastic surgery unit: implications for cosmetic surgery training. AB - One of the challenges facing our profession is the adequate training of plastic surgeons in the subspeciality of aesthetic surgery, in addition to covering the rest of the large curriculum. The UK's Chief Medical Officer, Professor Sir Liam Donaldson, has recently called for better training for doctors, better information for patients, and a touger regulatory structure for private cosmetic surgery. In this study, we show that the training of cosmetic procedures in our unit has risen steadily over the 6 year period studied. As part of our committment to improving training, our unit has recently organised a 3 month block soely dedicated to aesthetic surgery, allowing increasing exposure to cosmetic clinics and theatre sessions. It is clear that as a group, we must continue to develop robust training schemes to produce plastic surgeons able to cope with the demands of 21st Century healthcare, and ensure that the public does not fall prey to practitioners in unregulated clinics. PMID- 17349603 TI - Hypoplastic thumb in Gorlin's syndrome. AB - Gorlin's syndrome or naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder that predisposes to basal cell carcinomas of the skin, ovarian fibromas, and medulloblastomas. This condition is due to mutations in the Patched (PTCH) gene which maps to chromosome 9q22 and acts as a tumour suppressor gene. Gorlin's syndrome is characterized by the development of multiple jaw keratocysts and/or basal carcinomas. There is a distinctive coarse facial appearance with macrocephaly, frontal bossing and prognathism. Most individuals have skeletal anomalies such as bifid ribs or wedge-shaped vertebrae. We present a case in which the patient presented with bilateral thumb hypoplasia. Various hand deformities have been reported in patients with Gorlin's syndrome including short metacarpals, cutaneous syndactyly of the second and third fingers, and pre- or post-axial polydactyly, but hypoplasia of the thumb has not been reported previously. These features of Gorlin's syndrome may be helpful diagnostically. The thumbs should be examined carefully in Gorlin's syndrome patients as minor degrees of hypoplasia are easy to miss. However, they still needs a specialist input to give the patient an optimum function of the thumb and the hand. PMID- 17349604 TI - Clinical case of ossifying fasciitis of the hand. AB - Ossifying fasciitis is a rare benign tumour similar to nodular fasciitis histopathologically, but, morphologically, composed of metaplastic bone with calcification and chondroid differentiation. This lesion may easily be misinterpreted as malignancy, clinically and histologically, because it presents as a rapidly growing mass originating from subcutaneous or deep fascial tissues. These lesions are usually located in upper and lower extremities and trunk. We present a case in which, unusually, it was located in the flexor tendon sheath of the hand, which caused limitation of motion. Clinical suspicion and accurate histopathology of this rare benign lesion is important because it is commonly misdiagnosed as a malignancy and results in unnecessary aggressively wide resection. PMID- 17349605 TI - A technique to facilitate symmetrical and atraumatic placement of the core suture during flexor tendon repair. AB - We present a technique aiding symmetrical accurate and atraumatic placement of the core suture during tendon repair. This technique facilitates a neat repair and avoids unnecessary contact with the tendon during the insertion of the core suture. PMID- 17349606 TI - Camping gas burns: our experience. PMID- 17349607 TI - Reply to Islanded tripier flap--another useful variant. PMID- 17349608 TI - 'Recurrent' basal cell carcinomas may represent new primary neoplasias: differences between aggressive and nonaggressive histologic subtypes. PMID- 17349609 TI - An innovative technique for marking the donor site for full thickness skin grafts. PMID- 17349610 TI - The cost and risk impacts of rerouting railroad shipments of hazardous materials. AB - Rail shipments of hazardous materials expose the population near the routes to the possibility of an accident resulting in a spill. Rail routes are determined by economic concerns such as route length and the revenue generated for the originating carrier. In this paper we consider an alternate routing strategy that takes accident risks into account. We employ a model to quantify rail transport risk and then use a weighted combination of cost and risk and generate alternate routes. In some cases the alternate routes achieve significantly lower risk values than the practical routes at a small incremental cost. While there are generally fewer rerouting alternatives for rail than for road transport, considering the possible consequences of a train derailment we argue that risk should be taken into account when selecting rail routes and that the cost-risk tradeoffs should be evaluated. PMID- 17349611 TI - Light vehicle fuelling errors in the UK: the nature of the problem, its consequences and prevention. AB - Errors arising during the fuelling of light vehicles are increasing. It is estimated that around 300,000 misfuellings occurred in the UK in 2001 alone, with direct costs of approximately pound35 million and considerable inconvenience caused to all those involved. This study has investigated the causes of fuelling errors. A hierarchical task analysis of the fuelling of light vehicles was developed and data gathered from 23 individuals who had misfuelled. Errors were found to have occurred because the physical and psychological conditions on the filling station forecourt presented sufficient opportunity for an error producing sequence of events to be triggered. These occurred when specific factors were present either singly or in combination in the fuelling environment, creating an error 'pathway'. The probability of an error occurring is dependent upon the strength and type of influence these factors have on the performance of the fuelling task. It is proposed that errors are best prevented by applying ergonomic principles to the design, and/or modification of filling station layout and equipment. In this way, the error pathways may be broken and successful fuelling encouraged. PMID- 17349612 TI - Structure and conformation of the disulfide bond in dimeric lung surfactant peptides SP-B1-25 and SP-B8-25. AB - Raman spectroscopy was used to determine the conformation of the disulfide linkage between cysteine residues in the homodimeric construct of the N-terminal alpha helical domain of surfactant protein B (dSP-B(1-25)). The conformation of the disulfide bond between cysteine residues in position 8 of the homodimer of dSP-B(1-25) was compared with that of a truncated homodimer (dSP-B(8-25)) of the peptide having a disulfide linkage at the same position in the alpha helix. Temperature-dependent Raman spectra of the S-S stretching region centered at approximately 500 cm(-1) indicated a stable, although highly strained disulfide conformation with a chi(CS-SC) dihedral angle of +/-10 degrees for the dSP-B(1 25) dimer. In contrast, the truncated dimer dSP-B(8-25) exhibited a series of disulfide conformations with the chi(CS-SC) dihedral angle taking on values of either +/-30 degrees or 85+/-20 degrees . For conformations with chi(CS-SC) close to the +/-90 degrees value, the Raman spectra of the 8-25 truncated dimers exhibited chi(SS-CC) dihedral angles of 90/180 degrees and 20-30 degrees . In the presence of a lipid mixture, both constructs showed a nu(S-S) band at approximately 488 cm(-1), corresponding to a chi(CS-SC) dihedral angle of +/-10 degrees . Polarized infrared spectroscopy was also used to determine the orientation of the helix and beta-sheet portion of both synthetic peptides. These calculations indicated that the helix was oriented primarily in the plane of the surface, at an angle of approximately 60-70 degrees to the surface normal, while the beta structure had approximately 40 degrees tilt. This orientation direction did not change in the presence of a lipid mixture or with temperature. These observations suggest that: (i) the conformational flexibility of the disulfide linkage is dependent on the amino acid residues that flank the cysteine disulfide bond, and (ii) in both constructs, the presence of a lipid matrix locks the disulfide bond into a preferred conformation. PMID- 17349613 TI - Fast cortical oscillation after thalamic degeneration: pivotal role of NMDA receptor. AB - We examined electrophysiological and molecular changes of the thalamocortical system after thalamic degeneration in Purkinje cell degeneration (pcd) mice. In pcd mice, neurons in specific thalamic nuclei including the ventral medial geniculate nucleus began to degenerate around postnatal day 50, whereas the visual thalamic nucleus and nonspecific thalamic nuclei remained almost intact. In association with the morphological changes, auditory evoked potentials in the primary auditory cortex (AC) began to decrease gradually. Fast Fourier transform analysis of spontaneous cortical field potentials revealed that fast oscillation (FO) around 25 Hz occurred in the AC but not in the visual cortex. Quantitative mRNA analysis demonstrated that expression of the N-methyl-D-aspartate (NMDA) receptor was up-regulated in the AC but not in the visual cortex. Systemic administration of an NMDA antagonist abolished the FO in the AC. These results indicate that increased NMDA activity may cause the FO in the AC of pcd mice. PMID- 17349614 TI - Role of homologous ASP334 and GLU319 in human non-gastric H,K- and Na,K-ATPases in cardiac glycoside binding. AB - Cardiac steroids inhibit Na,K-ATPase and the related non-gastric H,K-ATPase, while they do not interact with gastric H,K-ATPase. Introducing an arginine, the residue present in the gastric H,K-ATPase, in the second extracellular loop at the corresponding position 334 in the human non-gastric H,K-ATPase (D334R mutation) rendered it completely resistant to 2mM ouabain. The corresponding mutation (E319R) in alpha1 Na,K-ATPase produced a approximately 2-fold increase of the ouabain IC(50) in the ouabain-resistant rat alpha1 Na,K-ATPase and a large decrease of the ouabain affinity of human alpha1 Na,K-ATPase, on the other hand this mutation had no effect on the affinity for the aglycone ouabagenin. These results provide a strong support for the orientation of ouabain in its biding site with its sugar moiety interacting directly with the second extracellular loop. PMID- 17349615 TI - Unsaturation at the surfactant head: influence on the activity of lipase and horseradish peroxidase in reverse micelles. AB - Influence of unsaturation present at the surfactant head on the activity of interfacially located enzyme, lipase, and horseradish peroxidase (HRP) is investigated in cationic reverse micelles of a series of surfactants having unsaturated (allyl and pyridinium moieties) as well as analogous saturated (n propyl and piperidinium moieties) polar head. Lipase activity increases with n propyl (saturated) substitution as the increase in the headgroup area (A(min)) presumably provides greater space for the enzyme to attain flexible conformation and increases the local concentrations of enzyme and substrate at the interface. In contrast, activity of lipase decreases with increasing number of allyl (unsaturated) substitution though A(min) gradually increased. Similar trend in deactivation was observed when unsaturation is present in cyclic ring (pyridine) at the surfactant head in comparison to the saturated analogue, piperidine. Circular dichroism (CD) spectra of lipase in reverse micelles indicate that ellipticity in the far-UV region increases with increasing unsaturation. Thus, lipase probably loses its alpha-helix content and thereby its activity. Inhibition of biocatalyst with increasing unsaturation at the polar head of surfactant is also observed in case of HRP, an oxidoreductase enzyme. PMID- 17349616 TI - Microarray analysis reveals that Type I interferon strongly increases the expression of immune-response related genes in Ubp43 (Usp18) deficient macrophages. AB - Type I interferon (IFN) contributes significantly to innate immune responses to pathogen infections in macrophages. Our previous studies demonstrate that Ubp43, an ISG15-specific isopeptidase, is highly expressed in macrophages and noncatalytically inhibits Type I IFN signaling. To understand the effect of Type I IFN and Ubp43 in macrophage activation, we analyzed the expression of IFN-beta stimulated genes in wild-type and Ubp43(-/-) bone marrow derived macrophages (BMMs). Here, we show that Ubp43 regulates IFN-beta stimulated genes at genome level. IFN hypersensitivity of Ubp43(-/-) BMMs resulted in the identification of 749 unique genes that are upregulated by IFN-beta, including a large group of previously unidentified IFN-stimulated genes. Functional analyses of these genes showed that Type I IFN strongly induced the expression of a group of immune response related genes, including genes for antigen presentation, antiviral responses, and chemokine and cytokine production. These results provide excellent biochemical support for the high resistance of viral and bacterial infection of Ubp43 knockout mice, suggesting that Ubp43 is a potential therapeutic target for the enhancement of immune responses against infections. PMID- 17349617 TI - Water and methanolic extracts of Salvia officinalis protect HepG2 cells from t BHP induced oxidative damage. AB - Common sage (Salvia officinalis L., Lamiaceae) is an aromatic and medicinal plant well known for its antioxidant properties. Some in vivo studies have shown the biological antioxidant effects of sage. However, the intracellular antioxidant mechanisms of action are still poorly understood. In this study, we evaluated the cytoprotective effects of two sage extracts (a water and a methanolic extract) against tert-butyl hydroperoxide (t-BHP)-induced toxicity in HepG2 cells. The most abundant phenolic compounds present in the extracts were rosmarinic acid and luteolin-7-glucoside. Both extracts, when co-incubated with the toxicant, protected significantly HepG2 cells against cell death. The methanolic extract, with a higher content of phenolic compounds than the water extract, conferred better protection in this in vitro model of oxidative stress with liver cells. Both extracts, tested in a concentration that protects 80% against cell death (IC(80)), significantly prevented t-BHP-induced lipid peroxidation and GSH depletion, but not DNA damage assessed by the comet assay. The ability of sage extracts to reduce t-BHP-induced GSH depletion by 62% was probably the most relevant contributor to the observed cytoprotection. A good correlation between the above cellular effects of sage and the effects of their main phenolic compounds was found. When incubated alone for 5h, sage extracts induced an increase in basal GSH levels of HepG2 cells, which indicates an improvement of the antioxidant potential of the cells. Compounds present in sage extracts other than phenolics may also contribute to this latter effect. Based in these results, it would be of interest to investigate whether sage has protective effects in suitable in vivo models of liver diseases, where it is known that oxidative stress is involved. PMID- 17349618 TI - The importance of 3,4-epoxy-1,2-butanediol and hydroxymethylvinyl ketone in 3 butene-1,2-diol associated mutagenicity. AB - 1,2:3,4-Diepoxybutane is hypothesized to be the main intermediate involved in mutagenicity following exposure to low levels of 1,3-butadiene (BD) in mice, while metabolites of 3-butene-1,2-diol (BD-diol) are thought to become involved in both rats and mice at higher exposures. BD-diol is biotransformed to hydroxymethylvinyl ketone (HMVK), a potentially mutagenic metabolite, and 3,4 epoxy-1,2-butanediol (EB-diol), a known mutagen. To determine the relative importance of HMVK and EB-diol in BD-diol associated mutagenesis, we have examined the dosimetry of a HMVK derived DNA adduct, as well as EB-diol derived DNA and hemoglobin adducts, in rodents exposed to BD-diol. We previously demonstrated similarities in the shapes of the dose-response curves for EB-diol derived DNA adducts, hemoglobin adducts, and Hprt mutant frequencies in BD-diol exposed rodents, indicating that EB-diol was involved in the mutagenic response associated with BD-diol exposure. To examine the role of HMVK in BD-diol mutagenicity, a method to quantify the alpha-regioisomer of HMVK derived 1,N(2) propanodeoxyguanosine (alpha-HMVK-dGuo) was developed. The method involved enzymatic hydrolysis of DNA, HPLC purification, and adduct measurement by liquid chromatography - tandem mass spectrometry. Intra- and inter-experimental variabilities were determined to be 2.3-18.2 and 4.1%, respectively. The limit of detection was approximately 5 fmol of analyte standard injected onto the column or 5 fmol/200 microg DNA. The method was used to analyze liver DNA from control female F344 rats and female F344 rats exposed to 36 ppm BD-diol. In addition, liver samples from female Sprague-Dawley rats exposed to 1000 ppm BD were analyzed. alpha-HMVK-dGuo was not detected in any of the samples analyzed. Several possible explanations exist for the negative results including the possibility that alpha-HMVK-dGuo may be a minor adduct or may be efficiently repaired. Alternatively, HMVK itself may be readily detoxified by glutathione (GSH) conjugation. While experiments must be conducted to understand the exact mechanism(s), these results, in addition to published EB-diol derived adduct dosimetry and existing HMVK derived mercapturic acid data, suggest that EB-diol is primarily responsible for BD-diol induced mutagenicity in rodents. PMID- 17349619 TI - Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH SY5Y human neuroblastoma cells. AB - Oxidative stress plays an important role in Alzheimer's disease and other neurodegenerative disorders. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L, shows potent antioxidant property. In this paper, the neuroprotective effects of salidroside on hydrogen peroxide (H2O2)-induced apoptosis in SH-SY5Y cells were investigated. Pretreatment with salidroside markedly attenuated H2O2-induced cell viability loss and apoptotic cell death in a dose-dependent manner. The mechanisms by which salidroside protected neuron cells from oxidative stress included the induction of several antioxidant enzymes, thioredoxin, heme oxygenase-1, and peroxiredoxin-I; the downregulation of pro-apoptotic gene Bax and the upregulation of anti-apoptotic genes Bcl-2 and Bcl-X(L). Furthermore, salidroside dose-dependently restored H2O2-induced loss of mitochondrial membrane potential as well as the elevation of intracellular calcium level. These results suggest that salidroside has protective effects against oxidative stress-induced cell apoptosis, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases implicated with oxidative stress. PMID- 17349620 TI - Attenuated function and expression of P-glycoprotein at blood-brain barrier and increased brain distribution of phenobarbital in streptozotocin-induced diabetic mice. AB - The aim of the study was to investigate whether diabetes mellitus modulated the function and expression of P-glycoprotein and the distribution of phenobarbital in the brain of 3-week streptozotocin-induced diabetic mice. P-glycoprotein function in blood-brain barrier was assessed by measuring the brain-to-plasma concentration ratios of rodamine123, a well-known P-glycoprotein substrate, in non-diabetic mice and diabetic mice. P-glycoprotein expression in the brain cortex was evaluated with western blot. Whether diabetes mellitus changed the distribution of phenobarbital (60 mg/kg, i.v.) in brain of mice was measured, and whether the changed distribution caused the difference of phenobarbital (80 and 100 mg/kg) -induced loss of the righting reflex in non-diabetic and diabetic mice were also investigated. The results showed that the brain-to-plasma concentration ratio value of rodamine123 in diabetic mice was significantly higher than that of non-diabetic mice, western blot suggested that the protein level of P glycoprotein in the brain of 3-week diabetic mice was significantly lower than that of non-diabetic mice, and insulin treatment restored the impairment of P glycoprotein. The exposure of phenobarbital in brain of diabetic mice was 1.30 fold of that of non-diabetic mice, while in plasma the fold was 1.09. The increased distribution of phenobarbital in the brain of diabetic mice significantly increased the duration of phenobarbital-induced loss of the righting reflex and reduced the latency time of loss of the righting reflex. All the results suggested that the function and expression of P-glycoprotein might be impaired and the brain distribution of phenobarbital was increased in brain of streptozotocin-induced diabetic mice. PMID- 17349621 TI - Effects of intrastriatal injections of glutamate receptor antagonists on the severity of paroxysmal dystonia in the dtsz mutant. AB - Imbalances of the glutamatergic system are implicated in the pathophysiology of various basal ganglia disorders, but few is known about their role in dystonia, a common neurological syndrome in which involuntary muscle co-contractions lead to twisting movements and abnormal postures. Previous systemic administrations of glutamate receptor antagonists in dtsz hamsters, an animal model of primary paroxysmal dystonia, exerted antidystonic effects and electrophysiological experiments pointed to an enhanced corticostriatal glutamatergic activity. In order to examine the pathophysiological relevance of these findings, we performed striatal microinjections of the alpha-amino-2,3-dihydro-5-methyl-3-oxo-4 isoxazolepropanoic acid (AMPA) receptor antagonist 2,3-dioxo-6-nitro-7 sulfamoylbenzo(f)quinoxaline (NBQX) and the N-methyl-D-aspartate (NMDA) receptor antagonists D(-)-2-amino-5-phosphopentanoic acid (AP-5), (R)-(+)-3-amino-1 hydroxypyrrolidin-2-one (HA-966) and dizocilpine (MK-801). The striatal application of NBQX reduced the severity and increased the latency to onset of dystonia significantly only at a dosage of 0.08 microg per hemisphere, lower (0.03 microg) and higher dosages (0.16 microg and 0.32 microg) failed to exert comparable effects on the severity. None of the striatal injected NMDA receptor antagonists influenced the severity of the dystonic attacks in the mutant hamster. The combined application of NBQX (0.08 microg) with AP-5 (1.0 microg) failed to exert synergistic antidystonic effects, but the beneficial effect on the severity of dystonia of the single application of NBQX was reproduced. Therefore, corticostriatal glutamatergic overactivity mediated by AMPA receptors, but not by NMDA receptors, is possibly important for the manifestation of dystonic attacks in the dtsz hamster mutant. PMID- 17349622 TI - The calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS reduces neurogenic increases in dural blood flow. AB - In an in vivo preparation of the exposed rat cranial dura mater electrical field stimulation causes increases in blood flow that are mainly due to the vasodilatory effect of calcitonin gene-related peptide (CGRP) released from meningeal afferents. In this preparation the effect of BIBN4096BS, a non-peptide competitive antagonist of CGRP receptors, was examined. Additionally, in an in vitro preparation of the hemisected rat skull the effect of BIBN4096BS on CGRP release stimulated by activation of meningeal afferents was analysed. Injection of BIBN4096BS at cumulative doses of 300 microg/kg and 900 microg/kg caused dose dependent inhibition of the electrically evoked blood flow increases. The basal blood flow and vital parameters were not significantly changed by any dose. In the hemisected skull BIBN4096BS at 10(-6) M did not alter the CGRP release evoked by depolarizing K(+) concentrations or antidromic electrical stimulation of the trigeminal ganglion. We conclude that neurogenic increases in dural blood flow are reduced by BIBN4096BS without changing basal vascular parameters. This peripheral effect may be important with regard to CGRP receptor inhibition as an antimigraine strategy. PMID- 17349623 TI - Gastrin-releasing peptide activates Akt through the epidermal growth factor receptor pathway and abrogates the effect of gefitinib. AB - Gastrin-releasing peptide (GRP) is a mitogen for lung epithelial cells and initiates signaling through a G-protein-coupled receptor, gastrin-releasing peptide receptor (GRPR). Because GRPR transactivates the epidermal growth factor receptor (EGFR), we investigated induction by GRP of Akt, an EGFR-activated signaling pathway, and examined effects of GRP on viability of non-small cell lung carcinoma (NSCLC) cells exposed to the EGFR tyrosine kinase inhibitor gefitinib. GRP induced Akt activation primarily through c-Src-mediated transactivation of EGFR. Transfection of dominant-negative c-Src abolished GRP induced EGFR and Akt activation. GRP induced release of amphiregulin, and pre incubation with human amphiregulin neutralizing antibody eliminated GRP-induced Akt phosphorylation. Pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 completely blocked GRP-initiated Akt phosphorylation. These results suggest that GRP stimulates Akt activation primarily via c-Src activation, followed by extracellular release of the EGFR ligand amphiregulin, leading to the activation of EGFR and PI3K. Pretreatment of NSCLC cells with GRP resulted in an increase in the IC(50) of gefitinib of up to 9-fold; this protective effect was mimicked by the pretreatment of cells with amphiregulin and reversed by Akt or PI3K inhibition. GRP appears to rescue NSCLC cells exposed to gefitinib through release of amphiregulin and activation of the Akt pathway, suggesting GRPR and/or EGFR autocrine pathways in NSCLC cells may modulate therapeutic response to EGFR inhibitors. PMID- 17349625 TI - Leishmania amazonensis: humoral response to amastigote excreted-antigens in murine leishmaniasis. AB - With the purpose of studying the antigenic role that factors excreted by Leishmania amastigotes might have during murine infection, immunoblots were carried out with sera from C57BL/6 and BALB/c mice infected with two strains of Leishmania (L.) amazonensis, NR and IFLA/BR. Both strains differ widely in virulence in BALB/c mice. BALB/c but not C57BL/6 sera recognized several excretion products. The excreted antigens showed a strong response towards IgG1 and IgG2a isotypes whilst they reacted only weakly against IgG2b and IgG3. A low molecular weight antigen (about 20 kDa) excreted by both Leishmania strains was strongly recognized by IgG1 from BALB/c mice sera infected with IFLA/BR, the most virulent strain. Sera from NR infected mice were incapable of recognizing this antigen in spite of its presence in NR excreted products. The results indicate that the humoral immune response to excreted antigens of amastigotes depends on both the host genetic background and the parasite strain. PMID- 17349624 TI - Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury. AB - We assessed the temporal and spatial characteristics of PN-induced oxidative damage and its relationship to calpain-mediated cytoskeletal degradation and neurodegeneration in a severe unilateral controlled cortical impact (CCI) traumatic brain injury (TBI) model. Quantitative temporal time course studies were performed to measure two oxidative damage markers: 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE) at 30 min, 1, 3, 6, 12, 24, 48, 72 h and 7 days after injury in ipsilateral cortex of young adult male CF-1 mice. Secondly, the time course of Ca(++)-activated, calpain-mediated proteolysis was also analyzed using quantitative western-blot measurement of breakdown products of the cytoskeletal protein alpha-spectrin. Finally, the time course of neurodegeneration was examined using de Olmos silver staining. Both oxidative damage markers increased in cortical tissue immediately after injury (30 min) and elevated for the first 3 6 h before returning to baseline. In the immunostaining study, the PN-selective marker, 3NT, and the lipid peroxidation marker, 4HNE, were intense and overlapping in the injured cortical tissue. alpha-Spectrin breakdown products, which were used as biomarker for calpain-mediated cytoskeletal degradation, were also increased after injury, but the time course lagged behind the peak of oxidative damage and did not reach its maximum until 24 h post-injury. In turn, cytoskeletal degradation preceded the peak of neurodegeneration which occurred at 48 h post-injury. These studies have led us to the hypothesis that PN-mediated oxidative damage is an early event that contributes to a compromise of Ca(++) homeostatic mechanisms which causes a massive Ca(++) overload and calpain activation which is a final common pathway that results in post-traumatic neurodegeneration. PMID- 17349626 TI - Trypanosoma cruzi: activity of essential oils from Achillea millefolium L., Syzygium aromaticum L. and Ocimum basilicum L. on epimastigotes and trypomastigotes. AB - Trypanocidal activity of clove (Syzygium aromaticum L.), basil (Ocimum basilicum L.) and yarrow (Achillea millefolium L.) essential oils and some of their constituents (eugenol and linalool) was investigated on Trypanosoma cruzi epimastigote and bloodstream trypomastigote forms. Steam distillation was used to isolate the essential oils, with chemical analyses performed by gas chromatography (GC) and GC coupled to mass spectrometry (GC-MS). The IC(50) (concentration that inhibits 50% parasite growth) of the oils and constituents upon T. cruzi was determined by cell counting in a Neubauer chamber. Cell morphology alterations were observed by scanning and transmission electron microscopy. Treatment with oils and constituents demonstrated that they inhibit parasite growth, with clove essential being the most effective one (IC(50)=99.5 microg/ml for epimastigotes and 57.5 microg/ml for trypomastigotes). Ultrastructural alterations were observed mainly in the nucleus. PMID- 17349627 TI - Properties of recombinant glycine decarboxylase P- and H-protein subunits from the cyanobacterium Synechocystis sp. strain PCC 6803. AB - The multi-enzyme complex glycine decarboxylase is important for one-carbon metabolism, essential for the photorespiratory glycolate cycle of plants, and comprises four different polypeptides, P-, H-, T-, and L-protein. We report on the production and properties of recombinant P-protein from the cyanobacterium Synechocystis and also describe features of recombinant H-protein from the same organism. The P-protein shows enzymatic activity with lipoylated H-protein and very low activity with H-apoprotein or lipoate as artificial cofactors. Its affinity towards glycine is unaffected by the presence and nature of the methyleneamine acceptor molecule. The cyanobacterial H-protein apparently forms stable dimers. PMID- 17349628 TI - Site specific phosphorylation of cytochrome c oxidase subunits I, IVi1 and Vb in rabbit hearts subjected to ischemia/reperfusion. AB - We have mapped the sites of ischemia/reperfusion-induced phosphorylation of cytochrome c oxidase (CcO) subunits in rabbit hearts by using a combination of Blue Native gel/Tricine gel electrophoresis and nano-LC-MS/MS approaches. We used precursor ion scanning combined with neutral loss scanning and found that mature CcO subunit I was phosphorylated at tandem Ser115/Ser116 positions, subunit IVi1 at Thr52 and subunit Vb at Ser40. These sites are highly conserved in mammalian species. Molecular modeling suggests that phosphorylation sites of subunit I face the inter membrane space while those of subunits IVi1 and Vb face the matrix side. PMID- 17349629 TI - Analysis of membrane topology of neutral sphingomyelinase 2. AB - Neutral sphingomyelinase 2 (nSMase2), which has two hydrophobic segments at its NH(2)-terminus, plays an important role in ceramide-mediated cell regulation. Here, we investigated the membrane topology of nSMase2. When a double-tagged nSMase2 at both the NH(2) and COOH termini, was overexpressed in MCF-7 cells, the signals from both tags were detected in the inner leaflet of the plasma membrane. Furthermore, insertion of a tag into the internal sequence and green fluorescent protein-fused deletion mutants revealed that the entire catalytic region of the protein was located on the cytosolic face of the membranes and each hydrophobic segment is integrated into the membranes, but unlikely to span the entire membrane. These results indicate the presence of the enzyme in the inner leaflet of plasma membrane. PMID- 17349630 TI - Attenuated cytotoxicity but enhanced betafibril of a mutant amyloid beta-peptide with a methionine to cysteine substitution. AB - Amyloid-beta peptide (Abeta), the major constituent of senile plaques in the Alzheimer's disease (AD) brain, is the main source of oxidative stress leading to neurodegeneration. The methionine residue in this peptide is reported to be responsible for neurotoxicity. Structurally similar substitution with methionine 35 replaced by cysteine in Abeta(40) was synthesized, and this result in enhanced beta-sheet structures according to both circular dichroism (CD) spectra and beta fibril specific fluorescence assay but attenuated cytotoxicity whether in the presence of copper or not. These findings may provide further evidence on disclosing the connection between amyloid beta-aggregation and Abeta-induced neurotoxicity. PMID- 17349631 TI - Protein kinase D enzymes are dispensable for proliferation, survival and antigen receptor-regulated NFkappaB activity in vertebrate B-cells. AB - To investigate the importance of protein kinase D (PKD) enzymes we generated a PKD-null DT40 B-lymphocyte cell line. Previously we have shown that PKDs have an essential role in regulating class II histone deacetylases in DT40 B-cells [Matthews, S.A., Liu, P., Spitaler, M., Olson, E.N., McKinsey, T.A., Cantrell, D.A. and Scharenberg, A.M. (2006) Essential role for protein kinase D family kinases in the regulation of class II histone deacetylases in B lymphocytes. Mol. Cell Biol. 26, 1569-1577]. We now show that PKDs are also required to regulate HSP27 phosphorylation in DT40 B-cells. However, in contrast to previous observations in other cell types, PKD enzymes do not regulate basic cellular processes such as proliferation or survival responses, nor NFkappaB transcriptional activity downstream of the B cell antigen receptor. Thus, PKDs have a selective role in DT40 B-cell biology. PMID- 17349632 TI - Histone deacetylase inhibitors suppress natural killer cell cytolytic activity. AB - Treatment of transformed cells from leukemia or solid tumors with histone deacetylase inhibitors (HDACi) was shown to increase their sensitivity to NK cell lysis. In this study, treatment of IL-2-activated NK cells with HDACi including suberoylanilide hydroxamic acid and valproic acid was studied. Both drugs at therapeutic concentrations inhibited NK cell cytotoxicity on human leukemic cells. This inhibition was associated with decreased expression and function of NK cell activating receptors NKp46 and NKp30 as well as impaired granule exocytosis. NFkappaB activation in IL-2-activated NK cells was inhibited by both HDACi. Pharmacologic inhibition of NFkappaB activity resulted in similar effects on NK cell activity like those observed for HDACi. These results demonstrate for the first time that HDACi prevent NK cytotoxicity by downregulation of NK cell activating receptors probably through the inhibition of NFkappaB activation. PMID- 17349633 TI - Kinetics of the plastoquinone pool oxidation following illumination Oxygen incorporation into photosynthetic electron transport chain. AB - The oxidation of the PQ-pool after illumination with 50 or 500 micromol quantam( 2)s(-1) was measured in isolated thylakoids as the increase in DeltaA(263), i.e., as the appearance of PQ. While it was not observed under anaerobic conditions, under aerobic conditions it was biphasic. The first faster phase constituted 26% or 44% of total reappearance of PQ, after weak or strong light respectively. The dependence on oxygen presence as well as the correlation with the rate of oxygen consumption led to conclusion that this phase represents the appearance of PQ from PQ(*-) produced in the course of PQH(2) oxidation by superoxide accumulated in the light within the membrane. PMID- 17349634 TI - DNA methylation imprints on the IG-DMR of the Dlk1-Gtl2 domain in mouse male germline. AB - Mouse genomes show a large cluster of imprinted genes at the Dlk1-Gtl2 domain in the distal region of chromosome 12. An intergenic-differentially methylated region (IG-DMR) located between Dlk1 and Gtl2 is specifically methylated in the male germline; IG-DMR regulates the parental allele-specific expression of imprinted genes. Here, we show the resetting of IG-DMR methylation marks during male germ-cell differentiation. For parental allele-specific methylation analysis, polymorphisms were detected in a 2.6-kb IG-DMR in three mouse strains. Bisulfite methylation analysis showed erasure of the marks by E14 and re establishment before birth. The IG-DMR methylation status was maintained in spermatogonia and spermatocytes of mature testes. The IG-DMR methylation status established before birth is thus maintained throughout the lifetime in the male germline. PMID- 17349635 TI - A remote but significant sequence homology between glycoside hydrolase clan GH-H and family GH31. AB - Although both the alpha-amylase super-family, i.e. the glycoside hydrolase (GH) clan GH-H (the GH families 13, 70 and 77), and family GH31 share some characteristics, their different catalytic machinery prevents classification of GH31 in clan GH-H. A significant but remote evolutionary relatedness is, however, proposed for clan GH-H with GH31. A sequence alignment, based on the idea that residues equivalent in the primordial catalytic GH-H/GH31 (beta/alpha)(8)-barrel may not be found in the present-day GH-H and GH31 structures at strictly equivalent positions, shows remote sequence homologies covering beta3, beta4, beta7 and beta8 of the GH-H and GH31 (beta/alpha)(8)-barrels. Structure comparison of GH13 alpha-amylase and GH31 alpha-xylosidase guided alignment of GH H and GH31 members for construction of evolutionary trees. The closest sequence relationship displayed by GH31 is to GH77 of clan GH-H. PMID- 17349636 TI - Upregulation of the TGFbeta signalling pathway by Bcr-Abl: implications for haemopoietic cell growth and chronic myeloid leukaemia. AB - Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by uncontrolled growth of progenitor cells expressing the tyrosine kinase fusion gene product, Bcr-Abl. At present, little is known regarding how TGFbeta, and downstream Smad transcription factors, influence CML cell proliferation in the context of Bcr-Abl expression. Here we show that ectopic Bcr-Abl expression dramatically increases TGFbeta/Smad-dependent transcriptional activity in Cosl cells, and that this may be due to enhancement of Smad promoter activity. Bcr-Abl expressing TF-1 myeloid cells are more potently growth arrested by TGFbeta compared to the parental TF-1 cell line. Additionally, growth of Bcr-Abl expressing CD34+ cells from chronic phase CML patients is inhibited by TGFbeta and, interestingly, treatment of a non-proliferating CD34+ CML cell sub population with the TGFbeta kinase inhibitor SB431542 enhanced cell death mediated by the Bcr-Abl inhibitor imatinib. Our data suggest that the expression of Bcr-Abl leads to hyper-responsiveness of myeloid cells to TGFbeta, and we hypothesise that this novel cross-regulatory mechanism might play an important role in maintaining the transformed progenitor cell population in CML. PMID- 17349637 TI - Detection of antizona pellucida antibodies in the sera from premature ovarian failure patients by a highly specific test. AB - OBJECTIVE: To develop a highly specific test for the detection of antizona pellucida (ZP) antibodies in the sera from premature ovarian failure (POF) patients. DESIGN: Laboratory study. SETTING: University hospital. PATIENT(S): Twenty-seven idiopathic POF patients, 30 control women, and 30 healthy males. INTERVENTION(S): Anti-ZP antibodies were detected by the microdot assay using a very small amount of human ZP or porcine ZP. The effect of anti-ZP antibodies on sperm-ZP binding was examined by hemizona assay. MAIN OUTCOME MEASURE(S): Results from the microdot assay and hemizona assay. RESULT(S): By the microdot assay using human ZP, the sera from POF patients reacted significantly stronger than those of control women and healthy males. However, no obvious difference could be found by the same assay using porcine ZP among these three groups. Anti-ZP antibodies against sera from some POF patients showed significant blocking effects on sperm-ZP binding assessed by hemizona assay. Anti-ZP antibodies were detected in 7 of 27 POF patients, while none were detected in control women and healthy males. CONCLUSION(S): Some idiopathic POF patients have anti-ZP antibodies in their sera, which were detected with high specificity by a newly developed microdot assay using a very small amount of human ZP. PMID- 17349638 TI - Combined intrauterine and twin cervical pregnancy managed by a new conservative modality. AB - OBJECTIVE: To describe a rare case of a heterotopic pregnancy with two gestational sacs in the cervix and one in the uterine cavity. DESIGN: Case report. SETTING: Tertiary university hospital. PATIENT(S): A 45-year-old woman was diagnosed with a triplet gestation 7 weeks following IVF treatment for primary infertility of 5 years' duration. Transvaginal ultrasound scan revealed three gestational sacs: one sac inside the uterine cavity containing a live fetus, and two sacs in the uterine cervix, one containing a live fetus and a second empty sac. INTERVENTION(S): Pregnancy termination was performed by selective intraarterial catheterization of the uterine artery, intraarterial administration of methotrexate, and uterine artery embolization with Gelfoam. MAIN OUTCOME MEASURE(S): Intra- or postprocedural complications and fertility preservation. RESULT(S): The pregnancy termination was successfully performed without intra- or postprocedural complications, with preservation of the patient's fertility. CONCLUSION(S): Intraarterial methotrexate with uterine vessel embolization is an effective conservative approach to heterotopic cervical pregnancy. PMID- 17349639 TI - Nitric oxide levels in women with missed and threatened abortion: results of a pilot study. AB - The aim of this study was to evaluate the systemic production of nitric oxide (NO) in missed and threatened abortion and in nonpregnant and regular pregnant controls with the purpose of defining its role in the mechanisms regulating the first-trimester pregnancy toward either positive or negative evolution. Patients with missed abortion showed serum NO levels clearly decreased compared with nonpregnant patients and patients with regular pregnancy and threatened abortion, supporting a direct functional role of the NO mediator in early embryonic development and confirming its importance in the uterus and cervix during abortion. PMID- 17349640 TI - Successful management of an extensive intracranial sinus thrombosis in a patient undergoing IVF: case report and review of literature. AB - OBJECTIVE: To report a successfully managed case of extensive intracranial sinus thrombosis that occurred during an IVF cycle, and to review the literature. DESIGN: Case report and review of literature. SETTING: University-affiliated teaching hospital. PATIENT(S): A 38-year-old nulliparous woman who developed severe ovarian hyperstimulation syndrome on luteal day (LD) 5 during an IVF cycle. Hemoconcentration was corrected, ascitis drained, and heparin prophylaxis started. On LD7, the patient complained of severe headache and neck pain. A magnetic resonance imaging (MRI) study of the head showed extensive cortical vein and dural sinus thrombosis, including the superior sagittal sinus and transverse sinuses. INTERVENTION(S): The patient was fully heparinized using low-molecular weight heparin. On LD15 she was discharged home on warfarin, after confirming a negative pregnancy test. Complete thrombophilia work-up was negative. MAIN OUTCOME MEASURE(S): Clinical outcome. RESULT(S): Repeat MRI 2 months later revealed patent superior sagittal sinus and transverse sinuses, unremarkable cortical veins, and no evidence of flow obstruction. The patient was asymptomatic, with no neurologic sequelae. CONCLUSION(S): Extensive intracranial sinus thrombosis in women undergoing IVF may present with minimal symptoms and can occur in the absence of pregnancy and thrombophilia and despite heparin prophylaxis and correction of hemoconcentration. Medical management was successful and left the patient with no neurologic sequelae. PMID- 17349641 TI - Preimplantation genetic screening as an alternative to prenatal testing for Down syndrome: preferences of women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. AB - OBJECTIVE: Although the primary goal of preimplantation genetic screening (PGS) is to increase pregnancy rates in women undergoing IVF/intracytoplasmic sperm injection treatment, it has been suggested that it may also be used as an alternative to prenatal testing for Down syndrome. DESIGN: Trade-off questionnaires. SETTING: Two university centers for reproductive medicine. PATIENT(S): Two hundred forty-four subfertile women. INTERVENTION(S): Scenarios with different pregnancy chances after PGS and with different risk reductions of a Down syndrome pregnancy were presented. MAIN OUTCOME MEASURE(S): Willingness to have PGS performed in the various scenarios. RESULT(S): In case PGS would discover all Down syndrome embryos without affecting pregnancy chances, 83% of the women would have PGS performed. If PGS lowered pregnancy chances from one in five to one in seven, 36% of the women preferred to have PGS performed. If PGS reduced the chance of a Down syndrome pregnancy with 80% without affecting pregnancy chances, 75% of the women would have PGS performed, and 31% of them would refrain from prenatal testing afterward. CONCLUSION(S): Most women favor PGS for Down syndrome screening, even if it is not 100% sensitive. The acceptability depends on the effect PGS has on pregnancy chances, and, to a lower extent on its sensitivity to detect Down syndrome embryos. PMID- 17349642 TI - Women with advanced-stage endometriosis and previous surgery respond less well to gonadotropin stimulation, but have similar IVF implantation and delivery rates compared with women with tubal factor infertility. AB - OBJECTIVE: To investigate the response to controlled ovarian hyperstimulation and ART outcomes in women with advanced-stage endometriosis and previous surgeries at the Yale IVF program between 1996 and 2002. DESIGN: Retrospective case control study. SETTING: Academic medical center. PATIENT(S): The study group consisted of 68 women who previously undergone laparoscopic surgery for advanced-stage endometriosis. The control group included 106 women with tubal-factor infertility. The women with endometriosis underwent 133 IVF-ET cycles and the control group 208 cycles. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF-ET. MAIN OUTCOME MEASURE(S): Response to gonadotropins, fertilization, cleavage, implantation, pregnancy, miscarriage, and live birth rates. RESULT(S): Lower peak E(2) levels, higher total gonadotropin requirements, lower oocyte yield, and higher cancellation rates were found in women with endometriosis compared with tubal-factor control subjects. However, no differences were found in fertilization, cleavage, implantation, pregnancy, miscarriage, and delivery rates between the endometriosis and tubal-factor groups. CONCLUSION(S): Women with advanced-stage endometriosis who have undergone previous surgery respond less well to gonadotropins than women with tubal-factor infertility. However, implantation, pregnancy, and delivery rates are similar, suggesting that embryo quality and uterine receptivity remains unaffected despite diminished ovarian reserve in women with endometriosis. PMID- 17349643 TI - A multicenter randomized, controlled study comparing laparoscopic versus minilaparotomic myomectomy: short-term outcomes. AB - OBJECTIVE: To compare the laparoscopic and minilaparotomic approaches for symptomatic uterine leiomyomas treatment in terms of safety and feasibility. DESIGN: Randomized controlled trial. SETTING: Three university departments of obstetrics and gynecology of Catanzaro, Rome, and Florence, Italy. PATIENT(S): One hundred thirty-six women wishing to conceive and candidate for myomectomy due to symptomatic uterine leiomyomas or unexplained infertility. INTERVENTION(S): Myomectomy through laparoscopic or minilaparotomic access. MAIN OUTCOME MEASURE(S): Surgical outcomes. RESULT(S): Leiomyoma enucleation and hysterotomy suturing times were significantly shorter after minilaparotomic myomectomy, whereas the degree of surgical difficulty was significantly higher for the laparoscopic myomectomy. Intraoperative blood loss, variation in hemoglobin levels, quantity of pain control drugs used postoperatively, and hospitalization were significantly lower in the laparoscopic group than in the minilaparotomic one. Our surgical outcomes were significantly influenced by specific investigational centers involved, and by leiomyoma dimensions and localizations. This last variable is the strongest predictor of surgical outcome. CONCLUSION(S): Laparoscopic and minilaparotomic approaches to myomectomy are two safe and minimally invasive surgical procedures. A careful evaluation of the dimensions and localizations of fibroids are needed to address to the right choice to the best approach. PMID- 17349644 TI - Bouc-Wen model parameter identification for a MR fluid damper using computationally efficient GA. AB - A non-symmetrical Bouc-Wen model is proposed in this paper for magnetorheological (MR) fluid dampers. The model considers the effect of non-symmetrical hysteresis which has not been taken into account in the original Bouc-Wen model. The model parameters are identified with a Genetic Algorithm (GA) using its flexibility in identification of complex dynamics. The computational efficiency of the proposed GA is improved with the absorption of the selection stage into the crossover and mutation operations. Crossover and mutation are also made adaptive to the fitness values such that their probabilities need not be user-specified. Instead of using a sufficiently number of generations or a pre-determined fitness value, the algorithm termination criterion is formulated on the basis of a statistical hypothesis test, thus enhancing the performance of the parameter identification. Experimental test data of the damper displacement and force are used to verify the proposed approach with satisfactory parameter identification results. PMID- 17349645 TI - Use of emergency contraceptive pills and condoms by college students: a survey. AB - OBJECTIVES: This study examined the intentions, knowledge, and attitudes of college students regarding the use of emergency contraceptive pills (ECPs) and condoms. DESIGN AND SETTING: A cross-sectional descriptive study was conducted at 16 Korean colleges. METHODS: Data were collected from March 15 to June 10, 2006 from a convenience sample of 1046 college students using a survey questionnaire. The survey included measures of demographic variables, intention to use ECPs (one item) and condoms (one item), knowledge about ECPs (12 items), and attitudes toward using ECPs (12 items) and condoms (16 items). All items except knowledge were rated on a 5-point Likert-type response format, with higher scores indicating greater intentions, more positive attitudes, and greater knowledge. RESULTS: Of the 1046 participants, 76.3% had heard of ECPs and 13.2% of the sexually active participants (n=190) had used them. Participants showed a general lack of knowledge about ECPs and misconceptions about their safety. The intentions of using ECPs and condoms were positively correlated with each other and with attitude such that the more positive the attitude, the greater their intention to use both ECPs and condoms. There were significant gender differences on many of the variables, in that female students had higher knowledge about ECPs, intention of using ECPs and condoms, and more positive attitude toward condoms than male students who had more positive attitudes toward ECPs. Females had more concerns about the safety of ECPs than males. CONCLUSIONS: The findings suggest that college students must be better informed about ECPs, and reassured about their safety. Additionally, promoting ECPs would not negatively affect condom use. Efforts are needed to disseminate up-to-date information to the general public and to develop educational and awareness programs to empower young people to make informed decisions about the use of ECPs and condoms. PMID- 17349646 TI - Bringing caring and competence into focus in gerontological nursing: a longitudinal, multi-method study. AB - BACKGROUND: The recent literature suggests that caring has become increasingly devalued as health systems focus primarily on cure. This is a worrying trend, particularly for gerontological nursing, where cure is often not possible. Consequently, work with older people is often not seen as an attractive career option, a perception that is frequently reinforced during students' practise placements, which exert a considerable influence on the values that inform their future professional practise. AIMS AND OBJECTIVES: To explore longitudinally the way that students experience their placement, and to identify the characteristics of an 'enriched' environment of care that potentially creates a positive view of work with older people. METHODS: A multi-method longitudinal study using a constructivist methodology and comprising both conceptual and empirical phases was undertaken. This paper concentrates on the results emerging from 57 focus groups completed over a 3 year period in four School's of Nursing in England, short visits to 33 placement areas and in-depth visits to seven placement areas. FINDINGS: The paper describes a temporal model of the student placement experience in which their focus of attention and effort varies over time. Five 'foci' are identified-self as focus, course as focus, professional care as focus, patient as focus, person as focus. The extent to which students are able to achieve person as focus is crucially dependant upon the input of their mentor, and their exposure to enriched environments of care that can be understood in terms of the 'senses framework'. RELEVANCE TO PRACTISE: The paper describes several important ways in which students' placement experiences can be enhanced, enabling them to form and consolidate a more rounded and positive view of gerontological nursing. Numerous practical suggestions for achieving an 'enriched' environment of learning that enables students to appreciate the value of care as well as cure are identified. PMID- 17349647 TI - Oxidative and nitrative changes seen in lipoproteins following exercise. AB - Oxidative damage to lipoproteins, in particular low density lipoprotein (LDL), is known to play a role in a number of diseases associated with ageing such as cardiovascular disease, atherosclerosis, arthritis, dementia and the metabolic syndrome. Physical activity or exercise can alter the balance of oxidative and anti-oxidative species within the human body. A number of studies have assessed the effect of exercise training or a single exercise bout on plasma lipid oxidation or nitration, protein oxidation and circulating lipoprotein oxidation, but results are extremely mixed and the message arising from current literature in regard to exercise and its effect upon the oxidative status of lipoproteins is somewhat confusing. This review aims to summarise the studies investigating the effect of exercise on lipoprotein oxidation and nitration, and highlight areas in need of future research. PMID- 17349648 TI - Determination of impurities in flame retardant monomer 2-carboxyl ethyl(phenyl) phosphinic acid by ion chromotography. AB - In this paper, a method based on ion chromatography (IC) with conductivity detector was developed for the determination of impurities including phenyl phosphinic acid (BPA), phenyl phosphonic acid (PPOA) and crylic acid in flame retardant monomer 2-carboxyl ethyl(phenyl) phosphinic acid (CEPPA). Under favorable chromatographic conditions, good linear relationship, sensitivity and reproducibility were obtained. Detection limits of BPA, PPOA and crylic acid were 1.5, 0.5, 0.4 microg l(-1), respectively. Relative standard deviations (RSD) of repeated analyses were less than 2.22% (n=10). The real samples (white crystal) have been tested and rate of recovery were 89-108%. It was confirmed that this method could be used in the analysis of flame retardant monomers. PMID- 17349649 TI - Extraction and clean-up strategies for the analysis of poly- and perfluoroalkyl substances in environmental and human matrices. AB - The rapidly expanding field of per- and polyfluorinated alkyl substances (PFASs) research has resulted in a wide range of analytical methodologies to determine the human and environmental exposure to PFASs. This paper reviews the currently applied techniques for sample pre-treatment, extraction and clean-up for the analysis of ionic and non-ionic PFASs in human and environmental matrices. Solid phase extraction (SPE) is the method of choice for liquid samples (e.g. water, blood, serum, plasma), and may be automated in an on-line set-up for (large volume) sample enrichment and sample clean-up. Prior to SPE, sample pre-treatment (filtration or centrifugation for water or protein precipitation for blood) may be required. Liquid-liquid extraction can also be used for liquid samples (and does not require above mentioned sample pretreatment). Solid-liquid extraction is the commonly applied method for solid matrices (biota, sludge, soil, sediment), but automation options are limited due to contamination from polytetrafluorethylene tubings and parts applied in extraction equipment. Air is generally preconcentrated on XAD-resins sandwiched between polyurethane foam plugs. Clean-up of crude extracts is essential for destruction and removal of lipids and other co-extractives that may interfere in the instrumental determination. SPE, (fluorous) silica column chromatography, dispersive graphitized carbon and destructive methods such as sulphuric acid or KOH treatment can be applied for clean-up of extracts. Care should be taken to avoid contamination (e.g. from sample bottles, filters, equipment) and losses of PFASs (e.g. adsorption, volatilization) during sampling, extraction and clean-up. Storage at -20 degrees C is generally appropriate for conservation of samples. PMID- 17349650 TI - Adsorption and micelle formation of alkylammonium chloride-alkyltrimethylammonium chloride mixtures. AB - The surface tension of the aqueous solutions of binary cationic surfactant mixtures of (1) dodecylammnonium chloride (DAC)-tetradecyltrimethylammonium chloride (TTAC), (2) decylammonium chloride (DeAC)-dodecyltrimethylammonium chloride (DTAC), and (3) DAC-DTAC was measured as a function of the total molality and composition of surfactants at 298.15 K. The compositions of surfactants in the adsorbed film and micelle were evaluated and the phase diagram of adsorption and that of micelle formation were constructed. Furthermore the excess Gibbs energies of adsorption and micelle formation were calculated to estimate the deviation from the corresponding ideal mixing. It was found that the surface and micelle are enriched in trimethylammonium salts in (1) and (2), while in ammonium salt in (3) compared to the bulk solution. On the other hand, the micelle is enriched in trimethylammonium salts compared to the surface at the critical micelle concentration (CMC) in all the systems. The miscibility of the surfactants was clarified from the standpoints of the structure of the head group and of the matching between the size of polar head group of surfactants and the difference in hydrocarbon chain length. PMID- 17349651 TI - Experimental investigation on bubble coalescence under nonuniform temperature distribution in reduced gravity. AB - Results on bubble coalescences from the space experiment of thermocapillary bubble migration conducted on board the Chinese 22nd recoverable satellite are presented in this paper. Some coalescences of large spherical bubbles under microgravity are observed through bubbles staying at the upper side of the test cell. The data of bubble coalescence time are recorded and compared with theoretical predictions, which is based on a theory to describe the tendency of coalescence connected to chemical potential difference. It is implied that the theory is applicable for the experimental data of bubble coalescence. Moreover, the angle between the line of two bubble centers and temperature gradient falled mostly in the range 20 degrees -40 degrees . PMID- 17349652 TI - A multiscale approach to ion diffusion in clays: building a two-state diffusion reaction scheme from microscopic dynamics. AB - The mobility of particles is generally lowered by the presence of a confining medium, both because of geometrical effects, and because of the interactions with the confining surfaces, especially when the latter are charged. The water/mineral interface plays a central role in the dynamics of ions. The ionic mobility in clays is often understood as an interplay between the diffusion of mobile ions and their possible trapping at the mineral surfaces. We describe how to build a two-state diffusion-reaction scheme from the microscopic dynamics of ions, controlled by their interaction with a mineral surface. The starting point is an atomic description of the clay interlayer using molecular simulations. These provide a complete description of the ionic dynamics on short time and length scales. Using the results of these simulations, we then build a robust mesoscopic (Fokker-Planck) description. In turn, this mesoscopic description is used to determine the mobility of the ions in the interlayer. These results can then be cast into a diffusion-reaction scheme, introducing in particular the fraction of mobile ions, or equivalently the distribution coefficient Kd. This coefficient is of great importance in characterizing electrokinetic phenomena in porous materials. PMID- 17349653 TI - Electrokinetic and surface chemical characterizations of an irradiated microfiltration polysulfone membrane: comparison of two irradiation doses. AB - The effect of ionizing radiation on the surface and electrokinetic characteristic parameters for a porous membrane of pore size 0.2 mum is determined and correlated with the irradiation dose (10 and 80 J/kg). Changes in NaCl permeability and membrane system electrical resistance determined from diffusion and impedance spectroscopy measurements are consistent with the increase of membrane pore radii/porosity, in agreement with SEM micrographs and reported results. Low irradiation dose seems to clean the membrane surface of impurities, according to XPS results, but the increase of irradiation doses could affect surface roughness. Due to the relatively high pore radius, ion transport numbers are practically independent of radiation and dose, but irradiation slightly modifies the membrane solution interface by increasing its weakly electronegative character, which could be of interest in the ultrafiltration of proteins or macromolecules. PMID- 17349654 TI - Proteomics of the flesh fly brain reveals an abundance of upregulated heat shock proteins during pupal diapause. AB - Most molecular work on insect diapause has focused on the expression of unique diapause transcripts, rather than the protein products. Here we present results from a proteomic comparison of diapausing and nondiapausing pupal brains. Proteins extracted from diapausing pupal brains of the flesh fly Sarcophaga crassipalpis were separated by two-dimensional gel electrophoresis and compared with those from nondiapausing pupal brains. Unique proteins and proteins present at different levels of abundance in diapausing and nondiapausing brains were identified by Nano-LC/MS/MS (capillary-liquid chromatography-nanospray tandem mass spectrometry). With this approach and Coomassie staining, we detected 37 diapause-unique or upregulated (> or = 2x) proteins, and 43 proteins that were downregulated or not present in diapause. Heat shock proteins (Hsp70 and several small Hsps) were among the most conspicuous brain proteins present in higher amounts during diapause. Brain proteins that were less abundant in diapause included phosphoenolpyruvate synthase, fatty acid binding protein, EG0003.7, and an endonuclease. Our 2-D proteome maps included several additional unknown proteins that were more abundant in either the diapause or nondiapause brains. While the mRNAs encoding some of these proteins (e.g. Hsps) were previously known to be associated with diapause, the other proteins were not known to be linked to diapause, thus suggesting that the proteomic approach nicely supplements the work done at the transcript level. PMID- 17349655 TI - Persistence of Metarhizium anisopliae incorporated into soilless potting media for control of the black vine weevil, Otiorhynchus sulcatus in container-grown ornamentals. AB - The objective of this study was to determine the persistence of Metarhizium anisopliae (F52), measured as infectivity against black vine weevil larvae, in a soilless potting medium at six wholesale nursery locations across the Willamette Valley, Oregon. A granule formulation (0.30 and 0.60 kg/m(3)) was incorporated into media at planting and fungal persistence determined over two growing seasons. The fungus persisted in the potting media over the duration of the experiment with 50-60% of the larvae exposed to treated media becoming infected at the end of the experiment. The percentage of infected larvae gradually declined from > or = 90% on week 3 to 40-60% by week 19. Larval infection rebounded over the fall and winter months of 2004 to 75-80% followed again by a slow decline over the course of the second growing season. PMID- 17349656 TI - Caveolin-1 inhibits matrix metalloproteinase-2 activity in the heart. AB - Apart from its ability to degrade extracellular matrix proteins, matrix metalloproteinase-2 (MMP-2) was recently revealed to have targets and actions within the cardiac myocyte. The localization of MMP-2 in caveolae of endothelial cells suggests that caveolin-1 (Cav-1) may play a role in regulating MMP-2. The caveolin scaffolding domain (CSD) of Cav-1 regulates several proteins including those involved with signaling cascades. Whether Cav-1 is responsible for regulating MMP-2 in the heart is unknown. Hearts from Cav-1(-/-) or Cav-1(+/+) mice were isolated and heart extracts or lipid raft enriched membrane fractions were prepared. MMP-2 activity in Cav-1(-/-) hearts was markedly enhanced when compared with Cav-1(+/+) hearts with no changes in MMP-2 protein levels between groups. In contrast, MMP-2 activity and protein level were greatly reduced in lipid raft enriched fractions of Cav-1(-/-) hearts. Purified CSD inhibited MMP-2 activity in a concentration-dependent manner as assessed using an in vitro degradation assay with a fluorogenic MMP-2 substrate (OmniMMP). These data suggest that Cav-1 plays a role in regulating MMP-2 activity. Cav-1 may thus be a novel mechanism to regulate MMP-2 activity in the heart. PMID- 17349657 TI - From the periplasmic signaling domain to the extracellular face of an outer membrane signal transducer of Pseudomonas aeruginosa: crystal structure of the ferric pyoverdine outer membrane receptor. AB - The pyoverdine outer membrane receptor, FpvA, from Pseudomonas aeruginosa translocates ferric pyoverdine across the outer membrane through an energy consuming mechanism using the proton motive force and the TonB-ExbB-ExbD energy transducing complex from the inner membrane. We solved the crystal structure of the full-length FpvA bound to iron-pyoverdine at 2.7 A resolution. Signal transduction to an anti-sigma protein of the inner membrane and to TonB-ExbB-ExbD involves the periplasmic domain, which displays a beta-alpha-beta fold composed of two alpha-helices sandwiched by two beta-sheets. One iron-pyoverdine conformer is bound at the extracellular face of FpvA, revealing the conformer selectivity of the binding site. The loop that contains the TonB box, involved in interactions with TonB, and connects the signaling domain to the plug domain of FpvA is not defined in the electron density following the binding of ferric pyoverdine. The high flexibility of this loop is probably necessary for signal transduction through the outer membrane. PMID- 17349658 TI - Protective effects of antioxidant medications on limb ischemia reperfusion injury. AB - BACKGROUND: N-acetylcysteine, beta-glucan, and coenzyme Q(10) were shown to have antioxidant and anti-inflammatory effects on reperfusion injury. The aim of our study was to determine and evaluate the effects of these agents on ischemia reperfusion injury of limb. MATERIAL AND METHOD: Forty-four New Zealand white rabbits, all female, weighing between 2.3 to 4.2 (mean 3.8) kg, were used in the study. Four study groups were arranged of 11 animals each, by randomization. The first group was the control group (Group C), the other groups were the Group Q, which was medicated with coenzyme Q10, the Group betaG, which was medicated with beta-glucan, and the Group N, medicated with N-acetylcysteine. After baseline measurements, for the ischemia-reperfusion experiments, common iliac artery was clamped and collateral flow was occluded by a rubber arterial tourniquet wrapped around the thigh at the proximal third of the leg. After 60 min of transient ischemic period, the limb was perfused for 180 min. After perfusion, biopsy was taken from the adductor magnus muscle. Second blood sampling was done after reperfusion period. Blood and tissue analysis were done and evaluated statistically. RESULTS: Baseline and post-reperfusion levels of glutathione peroxidase (GPx), super oxide dismutase (SOD), malonyldialdehyde (MDA), and nitric oxide (NO) changed significantly. While MDA levels increased in the control group, it decreased in the other study groups. The increase in GPx and SOD levels were significant in all groups except the control group. Levels of NO were found to have decreased in the control group, whereas it had increased in the other groups. CONCLUSION: Antioxidant medication may help lowering limb ischemia reperfusion injury. All mentioned medications in our study are shown to be able to have an effective role for preventing ischemia reperfusion injury to some extent through their antioxidant properties. PMID- 17349659 TI - A new modified technique for heterotopic femoral heart transplantation in rats. AB - BACKGROUND: Abbott developed the first experimental accessory heart transplant rat model in 1964. This intra-abdominal model required a labor-intensive aortic anastomosis. In 1971, Heron modified the operation by using sutureless cervical vessel anastomoses. Rao and Lisitza developed a femoral heart accessory transplant model in 1985. Our goal was to improve this femoral model for the study of cardiac transplantation between both syngeneic and allogeneic rats. METHODS: ACI and Lewis rats weighing 150 to 350 g were used as donors and recipients (n = 12). The left common carotid and left pulmonary arteries were anastomosed to the femoral artery and vein in an end-to-end fashion, respectively. Improved modifications included the use of hemostatic vessel clips, heparinization of both donor and recipient, a ventricular prolene stay-suture for secure graft placement, and transfemoral echocardiography (TFE). Total operative time averaged 61 +/- 12 minutes. RESULTS: Femoral accessory transplanted hearts (FATHs) allowed easier pulse palpation and access for TFE versus previously described cervical and intra-abdominal models. This modification allows precise detection of acute graft rejection (AGR) and is defined as absent ventricular contraction in the presence of anastomostic patency. CONCLUSIONS: Our new modified technique for heterotopic femoral heart transplantation in rats is a relatively easily learned and reproduced procedure that allows superior allograft access for palpation and improved echocardiographic assessment. Femoral heterotopic heart transplantation remains an effective model for allograft transplantation study. PMID- 17349660 TI - An unusual case of a spasticity-lacking phenotype with a novel SACS mutation. AB - The authors describe an unusual case of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) without leg spasticity, which is a core clinical feature of ARSACS. This is the second family with a spasticity-lacking phenotype in ARSACS. A peripheral nerve conduction study disclosed decreases in motor and sensory nerve conduction velocities with the disease progression. Although the leg spasticity is reported to become progressively worse during the disease and is prevalent in older patients, we first observed that the symptom had disappeared, probably due to the progressive peripheral nerve degeneration in the disease course. Thus, we should analyze the SACS gene even in cases of early onset cerebellar ataxia without spasticity. The patient had a novel homozygous 2 base pair deletion mutation (c.5988-9 del CT) of the SACS gene, but the genotype was different from that in our first family of this phenotype. A further genotype phenotype correlation study is required to clarify the molecular mechanism underlying 'sacsinopathies'. PMID- 17349661 TI - Cryptogenic multi-infarcts and cortico-subcortical dementia in a young adult. AB - INTRODUCTION: Etiology of stroke and dementia in young adults are challenging clinical problems, and these diseases often have devastating consequences. We present a case where a final etiologic diagnosis is not possible, in spite of an exhaustive study. CASE REPORT: A 34-year-old man presented with a 5-year history of transient neurological deficits. Examination disclosed a cortico-subcortical dementia, but no other deficits. Laboratory evaluation was unremarkable, including the basic vascular study, homocystein, immunologic study, ACE, serology for Lyme, syphilis and HIV, tests for mitochondrial cytopathy, CADASIL and Fabry's disease, and CSF study. Prothrombotic study was normal except for a heterozygous mutation for factor V Leiden and for methylene tetrahydrofolate reductase. Cardiac exams (electrocardiogram, transesophagic echocardiography and 24 h-ECG) were normal. Cervical and transcranial duplex ultrasound and magnetic resonance angiography (MRA)-were normal, except for a hypoplasic right vertebral artery. Brain magnetic resonance imaging revealed corticosubcortical atrophy and multiple infarcts. The patient was prescribed antiplatelet and statin therapy, and is presently clinically stabilized after 3 years of follow-up, scoring 2 in modified Rankin scale. DISCUSSION: Differential diagnosis of young onset vascular dementia is wide, including a number of rare sporadic and hereditary diseases. Although our case has a heterozygotic mutation for factor V Leiden, this might not explain the whole clinical picture; furthermore, there is no history of other vascular events, as venous thrombosis. An extensive investigation did not lead to a final etiological diagnosis. Nevertheless, even in these cases prevention with antiplatelet and statin might lead to clinical stabilization. PMID- 17349662 TI - Maternal leptin treatment during lactation programs the thyroid function of adult rats. AB - Recently, we showed that both maternal malnutrition during lactation and leptin treatment during the neonatal period program thyroid function. In this study we evaluate whether maternal leptin treatment during lactation programs thyroid function of the offspring in the adulthood. The dams were divided into 2 groups: Lep-daily sc single injected with 8 microg/100 g of body weight with recombinant rat leptin during the last 3 days of lactation and control group (C) that received the same volume of saline. The 180 day-old animals received a single i.p. injection of (125)I (2.22x10(4) Bq) and they were killed 2 h after the injection. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) and leptin concentrations were measured by radioimmunoassay. The milk of leptin-treated mothers on the last day of treatment had higher leptin (p<0.05) concentration. The pups of the leptin-treated mothers had at 21 days an unchanged T3, T4 and leptin serum concentrations with higher TSH (p<0.05). The offspring of Lep mothers had at 180 days a higher T3 (p<0.05) with normal thyroid (125)I uptake, T4 and TSH serum concentrations compared to the controls. So, the mother's hyperleptinaemia during lactation programs to a higher T3 serum concentration on the offspring, probably by a higher leptin transfer through the milk. PMID- 17349663 TI - Blood mononucleocytes are sensitive to the DNA damaging effects of iron overload- in vitro and ex vivo results with human and rat cells. AB - Iron exposure enhances colorectal carcinogeneis, by producing reactive oxygen species, which damage lipids, proteins and DNA. We recently demonstrated that ferric-nitrilotriacetate (Fe-NTA) damages DNA of human colon cells in different stages of malignant transformation. Opposed to this, little is known on systemic effects of iron and it is still difficult to determine the border between essential iron supplementation and iron overload in humans. The aim of this study was to determine whether Fe-NTA causes global and specific DNA damage in peripheral leucocytes. Human leucocytes were treated in vitro with Fe-NTA for 30 min at 37 degrees C. Male Sprague Dawley rats were fed (6 weeks) with an iron overload diet (9.9 g Fe/kg DM) and whole blood was collected. DNA damage was measured in human and rat blood cells using the alkaline version of the Comet Assay with repair specific enzymes. In human cells the distribution of TP53 in the comet images was detected using fluorescence in situ hybridization (Comet FISH) to measure DNA damage in the region of the TP53 gene. Fe-NTA (10-500 microM) was clearly genotoxic in human leucocytes in vitro, and also in leucocytes of rats fed the iron overload diet. The induced damage in human leucocytes was approximately two-fold that observed previously in human colon cells. Oxidized bases were induced by iron in rat leucocytes in vivo, while they were not induced in human leucocytes in vitro. Fe-NTA enhanced the migration of TP53 signals into the comet tail of human leucocytes, indicating a high susceptibility of this tumour-relevant gene towards DNA damage induced by iron overload. In conclusion, iron markedly induced DNA damage in human and rat leucocytes, which shows that these white blood cells are sufficiently sensitive to assess exposure to iron. The measurement of DNA damage in human leucocytes could be used as a sensitive biomarker to study iron overload in vivo in humans and thus to determine whether supplementation results in genotoxic risk. PMID- 17349664 TI - Molybdenum cofactor-dependent resistance to N-hydroxylated base analogs in Escherichia coli is independent of MobA function. AB - Lack of molybdenum cofactor (MoCo) in Escherichia coli and related microorganisms was found to cause hypersensitivity to certain N-hydroxylated base analogs, such as HAP (6-N-hydroxylaminopurine). This observation has lead to a previous proposal that E. coli contains a molybdoenzyme capable of detoxifying such N hydroxylated analogs. Here, we show that, unexpectedly, deletion of all known or putative molybdoenzymes in E. coli failed to reveal any base-analog sensitivity, suggesting that a novel type of MoCo-dependent activity is involved. Further, we establish that protection against the analogs does not require the common molybdopterin guanine-dinucleotide (MGD) form of the cofactor, but instead the guanosine monophosphate (GMP)-free version of MoCo (MPT) is sufficient. PMID- 17349665 TI - The use of infrared thermography as an early indicator of bovine respiratory disease complex in calves. AB - Bovine respiratory disease (BRD) complex causes considerable distress to domestic livestock and economic hardship to the beef industry. Furthermore, the resulting extensive use of antimicrobial treatments is a growing concern from the perspective of facilitating antibiotic resistant microbes. The earlier detection of BRD would enable an earlier, more targeted treatment regime and earlier isolation of infected individuals. The objective of the present study was to investigate the use of non-invasive infrared thermography in the early detection of BRD in cattle. Studies were conducted on 133 head of weaned calves. Data demonstrated that infrared thermography was able to identify animals at early stages of illness, often several days to over one week before clinical signs were manifest. Data indicated that 4-6 days prior to the onset of clinical symptoms of BRD, greater positive and negative predictive values and test efficiency for infrared thermography (80%, 65% and 71%, respectively) compared to the industry standard practice of clinical scoring (70%, 45% and 55%, respectively). PMID- 17349666 TI - The geomagnetic field influences the sensitivity of our eyes. AB - Experiments involving the orientation of animals, especially birds, have shown that the visual system and geomagnetic field are linked. On the basis of these findings, we have addressed the question of whether there is an influence of the geomagnetic field on light-sensitivity of the visual system in man. Here we report on measurements of the photopic sensitivity of the human visual system for a 0.5s test-stimulus without magnetic field and with the full local field of 48 microT rotated into the line of view. The experiments show that the geomagnetic field increases this sensitivity by 6-7%, depending on the stimulated area. Based on this increase the probable change in perception of the background luminance was calculated by the Weber-law. PMID- 17349667 TI - Form vision in the insect dorsal ocelli: an anatomical and optical analysis of the Locust Ocelli. AB - The dorsal ocelli are commonly considered to be incapable of form vision, primarily due to underfocused dioptrics. We investigate the extent to which this is true of the ocelli of the locust Locusta migratoria. Locust ocelli contain thick lenses with a pronounced concavity on the inner surface, and a deep clear zone separating retina and lens. In agreement with previous research, locust ocellar lenses were found to be decidedly underfocused with respect to the retina. Nevertheless, the image formed at the level of the retina contains substantial information that may be extractable by individual photoreceptors. Contrary to the classical view it is concluded that some capacity for resolution is present in the locust ocelli. PMID- 17349668 TI - Co-treatment of hydrogen sulfide and methanol in a single-stage biotrickling filter under acidic conditions. AB - Biofiltration of waste gases is cost-effective and environment-friendly compared to the conventional techniques for treating large flow rates of gas streams with low concentrations of pollutants. Pulp and paper industry off-gases usually contain reduced sulfur compounds, such as hydrogen sulfide and a wide range of volatile organic compounds (VOCs), e.g., methanol. It is desirable to eliminate both of these groups of compounds. Since the co-treatment of inorganic sulfur compounds and VOCs in biotrickling filters is a relatively unexplored area, the simultaneous biotreatment of H2S and methanol as the model VOC was investigated. The results showed that, after adaptation, the elimination capacity of methanol could reach around 236 g m(-3) h(-1) with the simultaneous complete removal (100%) of 12 ppm H2S when the empty bed residence time is 24 s. The pH of the system was around 2. Methanol removal was hardly affected by the presence of hydrogen sulfide, despite the low pH. Conversely, the presence of the VOC in the waste gas reduced the efficiency of H2S biodegradation. The maximal methanol removal decreased somewhat when increasing the gas flow rate. This is the first report on the degradation of methanol at such low pH in a biotrickling filter and on the co-treatment of H2S and VOCs under such conditions. PMID- 17349669 TI - Completely autotrophic nitrogen-removal over nitrite in lab-scale constructed wetlands: evidence from a mass balance study. AB - A mass-balance study was carried out to investigate the transformation of nitrogenous pollutants in vertical flow wetlands. Landfill leachate containing low BOD, but a high concentration of ammonia, was treated in four wetland columns under predominately aerobic conditions. Influent total nitrogen in the leachate consisted mainly of ammonia with less than 1% nitrate and nitrite, and negligible organic nitrogen. There was a substantial loss of total nitrogen (52%) in one column, whereas other columns exhibited zero to minor losses (<12%). Net nitrogen loss under study conditions was unexpected. Correlations between pH, nitrite and nitrate concentrations indicated the removal of nitrogen under study conditions did not follow the conventional, simplistic, chemistry of autotrophic nitrification. Through mass-balance analysis, it was found that CANON (Completely Autotrophic Nitrogen-removal Over Nitrite) was responsible for the transformation of nitrogen into gaseous form, thereby causing the loss of nitrogen mass. The results show that CANON can be native to aerobic engineered wetland systems treating wastewater that contains high ammonia and low BOD. PMID- 17349670 TI - Reactive transport of uranium(VI) and phosphate in a goethite-coated sand column: an experimental study. AB - The migration of uranium(VI) in subsurface environments is strongly influenced by its adsorption/desorption reactions at the solid/solution interface. Phosphate is often present in subsurface systems and was shown to significantly affect U(VI) adsorption in previous batch experiments. In this study, column experiments were conducted to investigate the effects of phosphate on U(VI) adsorption and transport under flow conditions. The adsorption of U(VI) and phosphate was very low on pure quartz sand with negligible effects on U(VI) and phosphate transport. However, U(VI) and phosphate transport was retarded in a column packed with goethite-coated sand. The presence of phosphate, either as a co-solute with U(VI) or pre-adsorbed, greatly increased U(VI) adsorption and retardation. U(VI) and phosphate adsorption in our column experiments were rate-limited, and the adsorption of U(VI) and phosphate was not reversible, with kinetic limitations more pronounced for desorption than for adsorption. This study demonstrated the importance of phosphate in controlling U(VI) mobility in subsurface environments and helped illustrate some phenomena potentially applicable to U(VI) adsorption and transport in natural systems, especially where U(VI) adsorption is rate limited. PMID- 17349671 TI - Regeneration of iron for trichloroethylene reduction by Shewanella alga BrY. AB - Zero valent iron (ZVI), the primary reactive material in several permeable reactive barriers, is often oxidized to ferrous or ferric iron, resulting in decreased reactivity with time. Iron reducing bacteria can reconvert the ferric iron to its ferrous form, prolonging the reduction of chlorinated organic contaminants. In this study, the reduction of Fe(II,III) oxide and Fe(III) oxide by a strain of iron reducing bacteria of the group Shewanella alga BrY(S. alga BrY) was observed in both aqueous and solid phases. S. alga BrY preferentially reduced dissolved ferric iron over the solid ferric iron. In the presence of iron oxide the Fe(II) ions reduced by S. alga BrY efficiently reduced trichloroethylene (TCE). On the other hand, Fe(II) produced by S. alga BrY covered the reactive surfaces of ZVI iron filings and inhibited the reduction of TCE by ZVI. The formation of precipitates on the iron oxide or Fe0 surface was confirmed by scanning electron microscopy. The results suggest that iron-reducing bacteria in the oxidized Fe0 barriers can enhance the removal rate of chlorinated organic compounds and influence on the long-term performance of Fe0 reactive barriers. PMID- 17349672 TI - Degradation of octylphenol and nonylphenol by ozone - part II: indirect reaction. AB - The indirect reaction of octylphenol (OP) and nonylphenol (NP) with hydroxyl radicals (*OH) during ozonation was investigated at pH values ranging from 6 to 9. A parameter Rct, representing the ratio of the *OH-exposure to the ozone exposure, was measured using a method involving a low concentration of p chlorobenzoic acid as a *OH-probe compound during the ozonation. By assuming that Rct is a constant value at a given pH, the second order rate constants of the alkylphenol reaction with hydroxyl radicals were determined as 1.4(+/-0.2) x 10(10) and 1.1(+/-0.2) x 10(10) M(-1) s(-1) for OP and NP, respectively. The proportions of each alkylphenol degraded by direct molecular ozone reaction and indirect hydroxyl radical reaction were predicted at different pH values. The contribution of indirect *OH reactions with each AP was found to represent over 50% of the total degradation for pH approximately 7, and the contribution increases substantially with pH>7. PMID- 17349673 TI - A comparative study in treating two VOC mixtures in trickle bed air biofilters. AB - Two independent parallel trickling bed air biofilters (TBABs) ("A" and "B") with two different typical VOC mixtures were investigated. Toluene, styrene, methyl ethyl ketone (MEK), and methyl isobutyl ketone (MIBK) were the target VOCs in the mixtures. Biofilter "A" was fed equal molar ratio of the VOCs and biofilter "B" was fed a mixture based on EPA 2003 emission report. Backwashing and substrate starvation operation were conducted as biomass control. Biofilter "A" and "B" maintained 99% overall removal efficiency for influent concentration up to 500 and 300 ppmv under backwashing operating condition, respectively. The starvation study indicated that it can be an effective biomass control for influent concentrations up to 250 ppmv for biofilter "A" and 300 ppmv for "B". Re acclimation of biofilter performance was delayed with increase of influent concentration for both biofilters. Starvation operation helped the biofilter to recover at low concentrations and delayed re-acclimation at high concentrations. Furthermore, re-acclamation for biofilter "B" was delayed due to its high toluene content as compared to biofilter "A". The pseudo first-order removal rate constant decreased with increase of volumetric loading rate for both biofilters. MEK and MIBK were completely removed in the upper 3/8 media depth. While biofilter depth utilization for the removal of styrene and toluene increased with increase of influent concentrations for both biofilters. However, toluene removal utilized more biofilter depth for biofilter "B" as compared to biofilter "A". PMID- 17349674 TI - Photochemical transformation of azoxystrobin in aqueous solutions. AB - The photochemical behaviour of azoxystrobin fungicide (AZX) in water was studied under laboratory conditions. Photodegradation was initiated using a solar simulator (xenon arc lamp) or a jacketed Pyrex reaction cell equipped with a 125 W, high-pressure mercury lamp. HPLC/MS analysis (APCI and ESI in positive and negative modes) was used to identify AZX photoproducts. The calculated polychromatic quantum efficiencies (phi) of AZX at pH 4.5, 7 and 9 were 5.42 x 10(-3), 3.47 x 10(-3) and 3.06 x 10(-3) (degraded molecules per absorbed photon), respectively. The relatively narrow range of values indicates the stability of AZX with respect to photodegradation in the studied pH range. Results from the HPLC/MS analysis suggest that the phototransformation of AZX proceeds via multiple, parallel reaction pathways including: (1) photo-isomerization (E-->Z), (2) photo-hydrolysis of the methyl ester and of the nitrile group, (3) cleavage of the acrylate double bond, (4) photohydrolytic ether cleavage between the aromatic ring giving phenol, and (5) oxidative cleavage of the acrylate double bond. PMID- 17349675 TI - Desorption of copper and cadmium from soils enhanced by organic acids. AB - The adsorption/desorption behavior of copper and cadmium on soils was investigated in this study. The adsorption isotherm of copper and cadmium conformed to Langmuir equation better than Freundlich equation. The effect of ionic strength, pH, and organic acid, including ethylenediamine tetraacetic disodium acid salt (EDTA), citric acid, oxalic acid and tartaric acid, on the desorption of copper and cadmium was studied. The desorption of copper and cadmium increased with the increase of ionic strength, while the desorption decreased with the rise of pH. The desorption of copper and cadmium enhanced by organic acids was influenced by pH. EDTA showed excellent enhancement on the desorption of both copper and cadmium; citric acid demonstrated great enhancement on the desorption of copper but negligible enhancement on the desorption of cadmium; oxalic acid enhanced the desorption of copper only at pH around 6.4 and enhanced the desorption of cadmium in the pH range from 6.4 to 10.7; tartaric acid slightly enhanced the desorption of copper but negligibly enhanced the desorption of cadmium. The desorption mechanism in the presence of organic acids were explained as the competition of complexation, adsorption and precipitation. The net effect determined the desorption efficiency. This study provided guidance for the selection of organic acids to enhance the electrokinetic (EK) remediation of copper and cadmium from contaminated soils. PMID- 17349676 TI - Degradation of octylphenol and nonylphenol by ozone - part I: direct reaction. AB - This aqueous reaction between ozone and two alkylphenols (APs), namely octylphenol (OP) and nonylphenol (NP), has been investigated. Both compounds are important endocrine disrupting chemicals, which arise from the biodegradation of alkylphenol ethoxylates and are often found at relatively high concentrations in wastewater effluents. In this paper the results of an experimental study are presented which provide values for the reaction rate constants between molecular ozone and undissociated OP and NP, and overall reaction rate constants for the degradation of the two APs at pH values in the range of 7-9. The kinetic rate constants for OP and NP degradation by molecular ozone were 4.33(+/-0.18) x 10(4) and 3.90(+/-0.10) x 10(4) M(-1) s(-1), and the reaction stoichiometry was similar in both cases and equal to approximately 1.3:1 ([O3]:[AP]). The overall second order reaction rate constants for the two APs increased significantly with increasing pH, which is believed to be mainly due to the increasing influence of indirect radical reaction with increasing pH; this aspect is considered in more detail in a companion paper. A preliminary investigation of the reaction mechanism suggests that an initial product of ozonation is hydroxyl-alkyl phenol. PMID- 17349677 TI - Chelate assisted phytoextraction of heavy metals from soil. Effect, mechanism, toxicity, and fate of chelating agents. AB - The low-cost, plant-based phytoextraction technique has often been described as a promising technique to remediate heavy metal contaminated agricultural land. The application of chelating agents has shown positive effects in increasing the solubility of heavy metals in soil and therefore in enhancing phytoextraction. This paper gives an overview of the chelating agents applied in recent studies. Various synthetic aminopolycarboxylic acids, such as ethylene diamine tetraacetic acid, and natural ones such as, ethylene diamine disuccinate and nitrilotriacetic acid, are described. Additionally, results of the application of natural low molecular weight organic acids, such as citric and tartaric acid are given. The effectiveness of these different chelating agents varies according to the plant and the heavy metals used. Furthermore, a focus is laid on the chelating agents fate after application and on its toxicity to plants and soil microorganisms, as well as it degradation. The rate of degradation is of great importance for the future of chelate assisted phytoextraction as it has a direct impact on the leaching probability. An effective prevention of leaching will be crucial for the acceptance and the economic breakthrough of enhanced phytoextraction, but a satisfactory solution to this key issue has so far not been found. Possibly further experiments in the field of enhanced phytoextraction will be able to solve this major problem, but over decades various greenhouse experiments and recently field experiments have resulted in different observations. Therefore, it is questionable if further research in this direction will lead to a promising solution. Phytoextraction has possibly reached a turning point in which it should distance itself from chelate assisted phytoextraction and focus on alternative options. PMID- 17349678 TI - Telemetered electromyography of peroneus longus in Varecia variegata and Eulemur rubriventer: implications for the functional significance of a large peroneal process. AB - A foot specialized for grasping small branches with a divergent opposable hallux (hallucal grasping) represents a key adaptive complex characterizing almost all arboreal non-human euprimates. Evolution of such grasping extremities probably allowed members of a lineage leading to the common ancestor of modern primates to access resources available in a small-branch niche, including angiosperm products and insects. A better understanding of the mechanisms by which euprimates use their feet to grasp will help clarify the functional significance of morphological differences between the euprimate grasp complex and features representing specialized grasping in other distantly related groups (e.g., marsupials and carnivorans) and in closely related fossil taxa (e.g., plesiadapiforms). In particular, among specialized graspers euprimates are uniquely characterized by a large peroneal process on the base of the first metatarsal, but the functional significance of this trait is poorly understood. We tested the hypothesis that the large size of the peroneal process corresponds to the pull of the attaching peroneus longus muscle recruited to adduct the hallux during grasping. Using telemetered electromyography on three individuals of Varecia variegata and two of Eulemur rubriventer, we found that peroneus longus does not generally exhibit activity consistent with an important function in hallucal grasping. Instead, extrinsic digital flexor muscles and, sometimes, the intrinsic adductor hallucis are active in ways that indicate a function in grasping with the hallux. Peroneus longus helps evert the foot and resists its inversion. We conclude that the large peroneal tuberosity that characterizes the hallucal metatarsal of prosimian euprimates does not correlate to "powerful" grasping with a divergent hallux in general, and cannot specifically be strongly linked to vertical clinging and climbing on small-diameter supports. Thus, the functional significance of this hallmark, euprimate feature remains to be determined. PMID- 17349679 TI - Production vs. respiration in river systems: an indicator of an "ecological status". AB - The Riverstrahler model of ecological functioning of large drainage networks validated on the Seine river system has been used for calculating the seasonal variations of Production and Respiration at various spatial scales (e.g. according to river orders). Based on the measurements of biological processes, the P/R ratio has led to an evaluation of the "ecological functioning", beyond the notion of "good ecological status". Furthermore, the effects, on the P/R ratio, of the geomorphological and climate factors characterizing the Hydro-Eco Regions (HER) of the Seine watershed have been quantitatively explored with the model. Whereas one finds a typical upstream-downstream pattern of the P/R ratio variations under the traditional rural conditions that prevailed in the Seine basin until the end of the 18th century, this pattern is strongly affected by the changes in urban populations and the implementation of wastewater collection and treatment, more than by the specificity of the physical factors characterizing the different HER. We have also found that autotrophy (a P/R ratio >1) might leads to eutrophication symptoms when P exceeds 1-2 mg C m(-2) d(-1) and that heterotrophy of the system (P/R ratio< 1) would reveal organic pollution when R exceeds 1-2 mg C m(-2) d(-1), stocks and fluxes of organic matter being expressed in carbon unit. Consequently, the P/R ratio appears as a good indicator of the perturbations caused by human activities in the watershed. The Riverstrahler model is able to quantify this effect. PMID- 17349680 TI - Improved cryosections and specific immunohistochemical methods for detecting hypoxia in mouse and rat cochleae. AB - The present study was undertaken to develop an improved cryoembedding method for analysis of mice and rat cochleae, which permits high-quality cryosections and preserves overall structure and cellular resolution as shown by hematoxylin/eosin staining. The preservation of morphology and antigenicity is mandatory to achieve optimal results. A total of 20 male cd/1 mice and 14 male Sprague-Dawley rats were used in experiments for optimization of preservation, fixative, decalcification, embedding and cryosectioning of cochleae from adult and aged rodents. In addition, a novel immunohistochemical procedure (using Hydroxyprobe-1 kit) was developed for detecting regions of hypoxia in mice and rat cochlea. This method employs a primary fluorescent-conjugated monoclonal antibody directed against pimonidazole protein adducts that are created in hypoxic tissues. Subsequent studies of hypoxia inducible factor-1alpha (HIF-1alpha) by immunofluorescence in the cochlea of these animals were performed in order to confirm that immunochemical detection of pimonidazole protein is representative of a hypoxic environment. We conclude that the present method results in high quality cryosections of cochlear tissues presenting good anatomical and histological preservation. Furthermore, our optimized procedures provide novel tools for the investigation of neuro-sensory-epithelium in physio-pathological situations associated with hypoxia and/or ischemia, such as inner ear development, plasticity, regeneration and senescence. PMID- 17349681 TI - Adherence with montelukast or fluticasone in a long-term clinical trial: results from the mild asthma montelukast versus inhaled corticosteroid trial. AB - BACKGROUND: Nonadherence with asthma therapy is common and may contribute to poor clinical outcomes. OBJECTIVE: To examine the effect of dosing frequency and mode of delivery of therapy on adherence and clinical outcomes. METHODS: We examined adherence in patients with mild persistent asthma (15-85 years) enrolled in a randomized study of montelukast (10 mg once daily) or fluticasone (88 microg, 2 puffs twice daily) during a 12-week double-blind treatment period (DB), followed by a 36-week open-label trial (OL). Adherence was monitored using eDEM for montelukast/placebo and MDILog devices for fluticasone/placebo. RESULTS: Participants used at least 1 puff of inhaled therapy on 83.3% DB/76.8% OL of days and at least 1 dose of oral therapy on 77.5%/71.4% of days (P < .0001). Subjects used inhaled therapy less than prescribed on 49.5%/57.5% of days, compared with 22.5%/28.6% of days for oral therapy (P < .0001). In the DB, a dose-response relationship was observed with fluticasone and asthma rescue-free days (P = .02) and FEV(1) percent predicted (P < .01) only for patients with FEV(1) < or = 86%. In the OL period, a dose-response relationship was observed with fluticasone and FEV(1) percent predicted (P < .001). CONCLUSION: Whereas subjects were more likely to use inhaled fluticasone/placebo at least once a day, subjects were more likely to take once-daily oral montelukast/placebo as prescribed. Clinical outcomes were inconsistently associated with adherence levels. CLINICAL IMPLICATIONS: Patients were less likely to be fully adherent with twice-daily therapy than with once-daily therapy, but most still achieved adequate asthma control. PMID- 17349682 TI - Further fatal allergic reactions to food in the United Kingdom, 1999-2006. PMID- 17349683 TI - Cloning, sequencing, and recombinant production of Sin a 2, an allergenic 11S globulin from yellow mustard seeds. AB - BACKGROUND: Among allergenic spices, mustard represents 1 of the most important in terms of allergenic potency and widespread use. An 11S globulin (Sin a 2) has been isolated from yellow mustard seeds and identified as a new major allergen. OBJECTIVE: Cloning and sequencing a cDNA encoding a Sin a 2 subunit and producing the allergen as a recombinant protein. METHODS: Sin a 2 subunit-encoding cDNA was amplified by polymerase chain reaction, cloned, and sequenced. The allergen was produced as a recombinant protein in Escherichia coli and used for enzyme-linked immunosorbent assay, immunoblotting, and inhibition experiments. Sera from patients with mustard allergy and an anti-polyhistidine monoclonal antibody were used. RESULTS: Sin a 2-specific cDNA comprises an open reading frame that encodes a protein of 510 amino acids, in which the first 23 residues correspond to the signal peptide. Sequence alignment with other allergenic 11S globulins showed levels of sequence identity ranging between 27% and 38%. Three peptides described as epitopes in Ara h 3 were moderately conserved in Sin a 2. Approximately 87% of the IgE binding to natural Sin a 2 was inhibited by the recombinant allergen using sera from patients with mustard allergy. CONCLUSION: The recombinant 11S globulin from yellow mustard seeds produced in E coli retained the IgE-binding capability of the natural allergen. CLINICAL IMPLICATIONS: The availability of Sin a 2 sequence and its recombinant production could help to develop future therapeutic approaches and might well open new investigation lines to resolve whether 11S globulins are proteins implicated in cross-reactivity processes involving mustard seeds. PMID- 17349684 TI - Not all farming environments protect against the development of asthma and wheeze in children. AB - BACKGROUND: In recent years, studies have shown a protective effect of being raised in a farm environment on the development of hay fever and atopic sensitization. Inconsistent data on the relation of farming to asthma and wheeze have raised some doubt about a true protective effect. OBJECTIVE: We sought to study the differential effects of farm-associated exposures on specific asthma related health outcomes. METHODS: The cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle study included 8263 school-age children from rural areas in 5 European countries. Information on farm-related exposures and health outcomes was obtained by using questionnaires. In subsamples allergen-specific IgE and RNA expression of CD14 and Toll-like receptor genes were measured, and dust from children's mattresses was evaluated for microbial components. RESULTS: Inverse relations with a diagnosis of asthma were found for pig keeping (odds ratio [OR], 0.57; 95% CI, 0.38-0.86), farm milk consumption (OR, 0.77; 95% CI, 0.60-0.99), frequent stay in animal sheds (OR, 0.71; 95% CI, 0.54-0.95), child's involvement in haying (OR, 0.56; 95% CI, 0.38-0.81), and use of silage (OR, 0.55; 95% CI, 0.31-0.98; for nonatopic asthma) and in Germany for agriculture (OR, 0.34; 95% CI, 0.22 0.53). Protective factors were related with higher expression levels of genes of the innate immunity. Potential risk factors for asthma and wheeze were also identified in the farm milieu. Levels of endotoxin and extracellular polysaccharides were related to the health outcomes independently of the farm exposures. CONCLUSIONS: The protective effect of being raised in a farm environment was ascribed to distinct exposures. CLINICAL IMPLICATIONS: The development of atopic sensitization and atopic and nonatopic asthma is most likely determined by different environmental factors, possibly reflecting distinct pathomechanisms. PMID- 17349685 TI - Three months' administration of anti-IgE to a patient with Churg-Strauss syndrome. PMID- 17349686 TI - Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. AB - BACKGROUND: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants. OBJECTIVE: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri. METHODS: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens. RESULTS: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected. CONCLUSION: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. CLINICAL IMPLICATION: Probiotics may reduce the incidence of IgE-associated eczema in infancy. PMID- 17349687 TI - Epididymal and ejaculated cat spermatozoa are resistant to cold shock but egg yolk promotes sperm longevity during cold storage at 4 degrees C. AB - The aims were to evaluate the susceptibility of feline ejaculated and epididymal spermatozoa to cold shock and to evaluate the effect of egg yolk in the preservation extender. Ejaculated and epididymal spermatozoa from eight males were subjected to a slow (0.5 degrees C/min) or a fast (3 degrees C/min) cooling rate with controls kept in room temperature. Ejaculated and epididymal spermatozoa from another eight males were cooled in a plain Tris buffer (Tris) or in Tris with 20% egg yolk (EYT) and evaluated for 96 h. Subjective motility (MOT), plasma membrane integrity (PMI), and acrosome integrity (ACRI) were evaluated. Cooling did not induce sperm damage regarding PMI (P=0.6) or ACRI (P=0.19) and chilled spermatozoa had better overall MOT (P=0.046) than controls. EYT was better for MOT (P>0.05) from 48 h of cold storage than Tris. EYT was also better for overall ACRI (P<0.0001) while Tris was better for overall PMI (P=0.0004). There were no interactions between time and treatment (P>0.05) for PMI or ACRI. Ejaculated spermatozoa had better overall MOT (P<0.05) and PMI (P<0.05) than epididymal spermatozoa, and higher ACRI in experiment 1 (P=0.0003) but not in experiment 2 (P=0.117). Source of spermatozoa did not affect the susceptibility to cooling or the effect of egg yolk as there were no interactions (P>0.05) between source of spermatozoa and treatment (cooling or control) or between time, source and extender (P>0.05). In conclusion cat spermatozoa were tolerant to cold shock and egg yolk was beneficial for preservation of MOT and ACRI but not PMI. PMID- 17349688 TI - Dentin decontamination using chloramine T prior to experiments involving bacteria. AB - OBJECTIVES: This study aims to investigate the importance of ISO11405 recommended storage regime for extracted teeth in surface disinfectant chloramine T (chlT) prior to use in biofilm or in vitro caries studies involving microorganisms. ChlT may be absorbed into dentin and undergoes breakdown with organic material. METHODS: Extracted roots were stored in chlT (2 days), rinsed and transferred to distilled deionised water. HPLC at regular intervals determined chlT elution. At 4 weeks roots were boiled in water and eluent assessed with HPLC. ChlT breakdown (+/-organic material) over time was monitored with HPLC. ChlT minimum inhibitory/bactericidal concentration (MIC/MBC) against Lactobacillus acidophilus was evaluated using L. acidophilus broth and chlT serial dilutions. RESULTS: No significant increase in chlT elution was detected between 2h and 4 weeks (ANOVA, Tukeys, p>0.05), although levels tended to increase with time. ChlT detected in water was 0.005%, corresponding to 0.05% in dentin. After boiling (4 weeks) chlT breakdown products in water corresponded to 0.015% in dentin. MIC/MBC of chlT against L. acidophilus was 0.031%. SIGNIFICANCE: ChlT breakdown is accelerated by organic material. L. acidophilus is highly sensitive to chlT. ChlT readily leaches from dentin but rinsing does not reduce chlT concentration below MIC/MBC. Low levels of chlT may remain but will probably be in a less active form. Teeth disinfected in chlT for use in research involving bacteria must be stored in distilled water for at least 2h to reduce chlT concentration below MBC, although longer will give greater elution and breakdown. PMID- 17349689 TI - Human early placental development: potential roles of the endometrial glands. AB - There is strong evidence that the endometrial glands play a key role in regulating placental development in many domestic species, but their contribution in the human has largely been ignored once implantation is complete. Here we re evaluate their role during the first trimester. Connections between the glands and the intervillous space have been observed from day 17 post-conception through to the end of the first trimester. In the absence of a maternal arterial supply to the early placenta it is believed that the carbohydrate- and lipid-rich secretions represent an important source of nutrients during the first trimester, and possibly the beginning of the second trimester. The secretions also contain a variety of growth factors that may regulate placental morphogenesis since their receptors are present on villous and extravillous trophoblast, and villous endothelial cells. Other components of the secretions may modulate immune responses and trophoblast invasion at the materno-fetal interface. We speculate that lactogenic hormones secreted by decidual cells and the syncytiotrophoblast may act in concert with human chorionic gonadotropin to stimulate the secretory activity of glandular epithelial cells during the first trimester. There is circumstantial evidence, but as yet no conclusive proof, that deficient glandular activity is associated with pregnancy failure in the human. PMID- 17349690 TI - Modeling Ca2+ signaling differentiation during oocyte maturation. AB - Ca2+ is a fundamental intracellular signal that mediates a variety of disparate physiological functions often in the same cell. Ca2+ signals span a wide range of spatial and temporal scales, which endow them with the specificity required to induce defined cellular functions. Furthermore, Ca2+ signaling is highly plastic as it is modulated dynamically during normal physiological development and under pathological conditions. However, the molecular mechanisms underlying Ca2+ signaling differentiation during cellular development remain poorly understood. Oocyte maturation in preparation for fertilization provides an exceptionally well suited model to elucidate Ca2+ signaling regulation during cellular development. This is because a Ca2+ signal with specialized spatial and temporal dynamics is universally essential for egg activation at fertilization. Here we use mathematical modeling to define the critical determinants of Ca2+ signaling differentiation during oocyte maturation. We show that increasing IP3 receptor (IP3R) affinity replicates both elementary and global Ca2+ dynamics observed experimentally following oocyte maturation. Furthermore, our model reveals that because of the Ca2+ dependency of both SERCA and the IP3R, increased IP3R affinity shifts the system's equilibrium to a new steady state of high cytosolic Ca2+, which is essential for fertilization. Therefore our model provides unique insights into how relatively small alterations of the basic molecular mechanisms of Ca2+ signaling components can lead to dramatic alterations in the spatio temporal properties of Ca2+ dynamics. PMID- 17349691 TI - Recent breakthroughs in the molecular mechanism of capacitative calcium entry (with thoughts on how we got here). AB - Activation of phospholipase C by G-protein-coupled receptors results in release of intracellular Ca(2+) and activation of Ca(2+) channels in the plasma membrane. The intracellular release of Ca(2+) is signaled by the second messenger, inositol 1,4,5-trisphosphate. Ca(2+) entry involves signaling from depleted intracellular stores to plasma membrane Ca(2+) channels, a process referred to as capacitative calcium entry or store-operated calcium entry. The electrophysiological current associated with capacitative calcium entry is the calcium-release-activated calcium current, or I(crac). In the 20 years since the inception of the concept of capacitative calcium entry, a variety of activation mechanisms have been proposed, and there has been considerable interest in the possibility of transient receptor potential channels functioning as store-operated channels. However, in the past 2 years, two major players in both the signaling and permeation mechanisms for store-operated channels have been discovered: Stim1 (and possibly Stim2) and the Orai proteins. Activation of store-operated channels involves an endoplasmic reticulum Ca(2+) sensor called Stim1. Stim1 acts by redistributing within a small component of the endoplasmic reticulum, approaching the plasma membrane, but does not appear to translocate into the plasma membrane. Stim1, either directly or indirectly, signals to plasma membrane Orai proteins which constitute pore-forming subunits of store-operated channels. PMID- 17349692 TI - Functional characterization of tumor necrosis factor superfamily 15 (TNFSF15) induced by lipopolysaccharides and Eimeria infection. AB - A full-length cDNA encoding chicken tumor necrosis factor superfamily 15 (TNFSF15) was isolated and its functional role was investigated. TNFSF15 transcripts were primarily expressed in spleen, liver, intestinal intraepithelial lymphocytes (IEL), peripheral blood lymphocytes and bursa. In vitro infection of HTC macrophages with three species of Eimeria sporozoites induced TNFSF15 gene expression. In vivo experiments revealed that TNFSF15 gene was highly increased following primary infections with Eimeria acervulina or Eimeria maxima. In contrast, no consistent changes in transcript levels were seen following primary infection with Eimeria tenella, or following secondary infection with any of the three Eimeria species. Following infection with E. acervulina and E. maxima, TNFSF15 transcripts were primarily expressed in intestinal CD4(+) and TCR2(+) IEL, respectively. A dose-dependent cytotoxic effect of recombinant TNFSF15 protein was observed on HTC and LSCC-RP9 tumor cells. These results indicate that TNFSF15 plays an important role in local inflammatory response to Eimeria. PMID- 17349693 TI - Molecular characterisation of Lac s 1, the major allergen from lettuce (Lactuca sativa). AB - BACKGROUND: IgE sensitisation to non-specific lipid transfer proteins (nsLTP), e.g., Pru p 3 the major allergen from peach and most important allergenic LTP, is strongly associated with severe symptoms in food allergic patients. Lac s 1, a member of the nsLTP protein family, was recently identified as major allergen in lettuce (Lactuca sativa), but has not yet been investigated on the molecular basis. OBJECTIVE: Molecular characterisation and immunological comparison of Lac s 1 to peach allergen Pru p 3. METHODS: Lac s 1 cDNA was cloned by RT-PCR and natural (n) Lac s 1 was purified by a two-step chromatography. Protein structure was verified by N-terminal sequencing, mass spectrometry, and circular dichroism spectroscopy. Immunoblotting, ImmunoCAP, and competitive IgE binding experiments were performed to study the IgE sensitisation pattern and cross-reactivity with Pru p 3. Allergenic potency was analysed by histamine release assay. RESULTS: Twenty-nine lettuce allergic patients, with or without concomitant peach allergy, and 19 peach allergic patients without lettuce allergy were included in this study. IgE reactivity to lettuce was due to mono-sensitisation to Lac s 1 or cross-reactive glycan structures. Two Lac s 1 isoforms were identified which showed amino acid identity (aa-id) of 62% to each other, up to 66% to Pru p 3, and 72% to the N-terminal peptide of plane pollen LTP Pla a 3. The prevalence of IgE binding to nLac s 1 was 90% using lettuce extract in immunoblotting experiments. Enhanced sensitivity was observed in ImmunoCAP using purified nLac s 1 in comparison to extracts (93% versus 76%). Although IgE sensitisation to Lac s 1 and Pru p 3 was strongly associated, the two LTPs showed different IgE binding properties. Sensitisation to LTPs does not necessarily reflect the clinical disease, but Lac s 1 was capable of triggering histamine release as shown by positive skin test results in Lac s 1 mono-sensitised patients and by in vitro mediator release assays. CONCLUSION: Purified nLac s 1 will enhance the sensitivity in component resolved diagnosis of lettuce allergy. Similar to other cross-reactive food allergies, exclusive testing of IgE reactivities to LTP cannot be used as biomarker for clinical relevance. Our data provide indirect evidence that Pru p 3 might act as the primary sensitising agent in patients allergic to both lettuce and peach. PMID- 17349694 TI - Transcriptome analysis of human immune responses following live vaccine strain (LVS) Francisella tularensis vaccination. AB - The live vaccine strain (LVS) of Francisella tularensis is the only vaccine against tularemia available for humans, yet its mechanism of protection remains unclear. We probed human immunological responses to LVS vaccination with transcriptome analysis using PBMC samples from volunteers at time points pre- and post-vaccination. Gene modulation was highly uniform across all time points, implying commonality of vaccine responses. Principal components analysis revealed three highly distinct principal groupings: pre-vaccination (-144 h), early (+18 and +48 h), and late post-vaccination (+192 and +336 h). The most significant changes in gene expression occurred at early post-vaccination time points (or=1 reactor to the tuberculin skin test). Biological differences are expected in the transmission dynamics, and hence risk factors for bTB breakdown, on farms where infection persists in the herd compared to farms where infection is more sporadic or short-lived. Comparative case-control studies were performed to test farm management practices as potential risk factors for transient (under breakdown restrictions for 6 months) bTB breakdown over 5 years (1995-1999) on 179 and 171 UK cattle farms, respectively. Farms were characterised for badger sett density and farm habitat composition by ground survey, farmers were questioned retrospectively on management practices, and cases and controls were identified from national tuberculin test records. Controlling for routine tuberculin testing interval, log transformed herd size, regional location, badger sett density and farm habitat complexity, multivariable logistic regression identified increased odds of both transient and persistent breakdown on farms that bought-in cows (odds ratio (OR)>or=4.9; 95% confidence interval (CI)>or=1.1;22.8). In addition, the purchase of >50 head of cattle (OR=4.0, 95% CI=1.0;16.0) and the storage of manure for >or/=6 months (OR=4.4; 95% CI=1.3;15.4) were risk factors for transient breakdown, whereas the use of silage clamps (OR=9.1; 95% CI=2.0;40.8) increased the risk of persistent breakdown. Decreased odds of both transient and persistent breakdown were associated with higher stocking densities (>3cattle/ha) (OR8.0gNeuAcL(-1)h(-1). In this process, the expensive activator, ATP, necessary for maximal activity of GlcNAc 2-epimerase in free enzyme system can be omitted. PMID- 17349708 TI - Construction of recombinant Escherichia coli D11/pMSTO and its use in enzymatic preparation of 7-aminocephalosporanic acid in one pot. AB - The main drawback in the industrial production of 7-aminocephalosporanic acid is the accumulation of intermediate (AKA-7-ACA) and destruction of substrate (cephalosporin C) catalyzed by catalase and beta-lactamase. To overcome the adverse effect of these enzymes on the conversion process, Escherichia coli D11 with mutation of katG, katE and ampC genes was constructed by P1 phage transduction, which enabled it not to produce catalase and beta-lactamase, respectively. At the same time, recA mutation in D11 increased the stability of foreign plasmid. With D11 used as host, both d-amino acid oxidase and GL-7-ACA acylase were cloned and expressed by the recombinant plasmids of pMSS or pMSTO, and the production of two enzymes could be increased by addition of 1.0% glucose. Cells of recombinant strain D11/pMSTO could directly convert cephalosporin C into 7-aminocephalosporanic acid at 25 degrees C, with the yield of more than 74%. The data suggested that the constructed D11/pMSTO could be an alternative catalyst for production of 7-aminocephalosporanic acid in one pot. PMID- 17349709 TI - Expression, purification and characterization of human IFN-lambda1 in Pichia pastoris. AB - Interferon-lambda (IFN-lambda) is a newly identified IFN family which belongs to the class II cytokines. The three members of this family represent antiviral activities like other IFNs. In the present study, recombinant human IFN-lambda1 (rhIFN-lambda1) was produced by using the methylotrophic yeast Pichia pastoris (P. pastoris) expression system. cDNAs encoding amino acids 23-200 or 20-200 of human IFN-lambda1 were cloned and joined to sequence encoding the leader region (prepro segment) of the precursor of Saccharomyces cerevisiae alpha-factor. The two hybrid genes were subcloned into yeast integrative vector pAO815 separately to construct expression plasmids bearing four tandem copies of IFN-lambda1 expression cassettes. The expression plasmids were then used to transform into P. pastoris strain GS115, resulting in recombinant strains GS115/IFNlambda1P and GS115/IFNlambda1G with Mut(+) or Mut(s) phenotype. rhIFN-lambda1 was secreted into the medium upon methanol induction. In GS115/IFNlambda1P, however, KEX2 cleavage for mature rhIFN-lambda1 generation was inhibited by a proline at [Formula: see text] and the products were different from anticipation. GS115/IFNlambda1G strain secreted two forms of mature rhIFN-lambda1 with the same N-terminal sequence and different molecular weight. Periodic acid-Schiff (PAS) staining indicated that these proteins were glycosylated. The yield of low glycosylated rhIFN-lambda1 in GS115/IFNlambda1G strain was approximately 65 mg l( 1) in shaking flasks, representing around 57% of the total secreted proteins. rhIFN-lambda1 was purified by cation exchange chromatography and gel filtration. The purified rhIFN-lambda1 showed specific efficiency to activate signal transducer and activator of transcription 1 (STAT1) and STAT2 that was comparable to that of commercial IFNalpha2a. PMID- 17349710 TI - Quasispecies and its impact on viral hepatitis. AB - Quasispecies dynamics mediates adaptability of RNA viruses through a number of mechanisms reviewed in the present article, with emphasis on the medical implications for the hepatitis viruses. We discuss replicative and non replicative molecular mechanisms of genome variation, modulating effects of mutant spectra, and several modes of viral evolution that can affect viral pathogenesis. Relevant evolutionary events include the generation of minority virus variants with altered functional properties, and alterations of mutant spectrum complexity that can affect disease progression or response to treatment. The widespread occurrence of resistance to antiviral drugs encourages new strategies to control hepatic viral disease such as combination therapies and lethal mutagenesis. In particular, ribavirin may be exerting in some cases its antiviral activity with participation of its mutagenic action. Despite many unanswered questions, here we document that quasispecies dynamics has provided an interpretation of the adaptability of the hepatitis viruses, with features conceptually similar to those observed with other RNA viruses, a reflection of the common underlying Darwinian principles. PMID- 17349713 TI - [Testing range of motion in cerebral palsy]. AB - OBJECTIVES: To propose a standardized test of joint range of motion in paediatric patients with cerebral palsy, based on the opinion of a cerebral palsy specialist group (physicians, physiotherapists and surgeons) and literature review. MATERIALS AND METHODS: A Delphi process was adapted to elaborate a complete test of lower-limb-joint range of motion. During the preparation phase, a pilot committee selected a list of items compiled from literature search and personal experience. A first questionnaire was proposed to 16 experts, then six discussion meetings followed. From the results, the pilot committee prepared a second questionnaire for the experts and finalized the complete test of joint range of motion. RESULTS: The complete test includes 24 items related to goniometric measurements in supine and prone positions. Principal conditions necessary for an accurate exam are included. Further, a testing guide with visuals of the proposed exam techniques was developed. CONCLUSIONS: The standardized testing of lower limb-joint range of motion will allow for better communication between clinicians and will facilitate the development of a database. Care should be taken in the interpretation of the joint range-of-motion test results and realized only after reliability analysis of the test, especially interobserver reliability. A further step would be to develop an outpatient booklet for cerebral palsy that shows growth and weight curves, joint range-of-motion curves and curves of the principal radiographic measurements during growth. PMID- 17349712 TI - Estradiol loaded PLGA nanoparticles for oral administration: effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo. AB - The present investigation was aimed at optimization of estradiol loaded PLGA nanoparticulate formulations resulting in improved oral bioavailability and sustained release of estradiol by varying the molecular weight and copolymer composition of PLGA. Nanoparticles were prepared following emulsion-diffusion evaporation method employing didodecyldimethyl ammonium bromide (DMAB) as stabilizer. The effect of polymer molecular weight and copolymer composition on particle properties and release behavior (in vitro and in vivo) has been reported. Drug release in vitro decreased with increase in molecular weight and lactide content of PLGA. Zero order release was obtained with low molecular weight (14,500 and 45,000 Da) PLGA, while high molecular weight (85,000 and 213,000 Da) and different copolymer compositions followed square root of time (Higuchi's pattern) dependent release. The bioavailability of estradiol from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg estradiol/rat. The in vivo performance of the nanoparticles was found to be dependent on the particle size, polymer molecular weight and copolymer composition. The C(max) of drug in the plasma was dependent on the polymer molecular weight and composition while particle size was found to influence the duration of release, suggesting smaller is better. The histopathological examination revealed absence of any inflammatory response with the formulations prepared of low/high molecular weight or high lactide content polymers for the studied period. Together, these results indicate that nanoparticulate formulations are ideal carriers for oral administration of estradiol having great potential to address the dose related issues of estradiol. PMID- 17349711 TI - Human immunodeficiency virus (HIV-1) Vpr induced downregulation of NHE1 induces alteration in intracellular pH and loss of ERM complex in target cells. AB - Human immunodeficiency virus type 1 (HIV-1) Vpr is known to dysregulate host cellular functions through its interaction with cellular proteins. Using a protein array we assessed Vpr-mediated differential regulation of host cellular proteins expression. Results demonstrated that Vpr differentially regulated host factors that are involved in functions, such as cell proliferation, differentiation and apoptosis. One of the most highly downregulated proteins attained was the sodium hydrogen exchanger, isoform 1 (NHE1), which showed a significant (60%) decrease in HIV-1 Vpr(+) virus infected cells as compared to HIV-1 Vpr(-) virus infected control. NHE1 downregulation further led to acidification of cells and was directly correlated with loss of ezrin, radixin and moesin (ERM) protein complex and decreased AKT phosphorylation. Vpr-mediated NHE1 dyregulation is in part through GR pathway as GR antagonist, mifepristone reversed Vpr-induced NHE1 downregulation. PMID- 17349714 TI - Stem cells therapy for type 1 diabetes. AB - In this article, we have reviewed the developments of studies of stem cells therapy for type 1 diabetes since this century. Review of the literature was based on computer searches (PubMed) and our studies. Type 1 diabetes can now be ameliorated by islet transplantation, but this treatment is restricted by the scarcity of islet tissue. Hopes for a limitless supply of a substitute for primary islets of Langerhans and progress in stem cell biology have led to research into the feasibility of stem/progenitor cells to generate insulin producing cells to use in replacement therapies for diabetes. An increasing body of evidence indicated that, in addition to embryonic stem cells, several potential adult stem/progenitor cells, derived from pancreas, liver, spleen, and bone marrow could differentiate into insulin-producing cells in vitro or in vivo. However, significant controversy currently exists in this field. Moreover, safe suppression of autoimmunity or specific tolerance to auto-antigens for patients with type 1 diabetes must be achieved before this promising new technology can lead to a great progress in clinical practice. To prevent type 1 diabetes through genetic engineering of hematopoietic stem cells represents another new strategy. Much basic research is still required. PMID- 17349715 TI - Wheat genotypes show contrasting abilities to recover from anoxia in spite of similar anoxic carbohydrate metabolism. AB - Physiological and metabolic responses to anoxia and reaeration were compared for 4-7-day-old seedlings of 11 genotypes of wheat (Triticum aestivum) with reputed differences in waterlogging tolerance. Genotypes differed in seminal root elongation, and recovery of root tissue K(+) concentration, during reaeration following 72 h anoxia. Post-anoxic recovery ranged from complete (100% retention of seminal root elongation potential) to almost nil (death of all seminal root apices and inability to recover K(+) concentration). The anoxia tolerance ranking of the genotypes based on these parameters corresponded with that of their reputed waterlogging tolerance, but with some exceptions. However, the differences in anoxia tolerance of the seedlings could not be explained by differences in capacity for ethanol production. A decreased ability to utilise seed starch reserves under anoxia, due to inadequate levels of alpha-amylase activity at the time anoxia was imposed, was apparent in all genotypes. PMID- 17349716 TI - Primary mucosal melanoma. AB - Primary mucosal melanomas are rare, biologically aggressive neoplasms. The distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites is 55.4%, 18.0%, 23.8%, and 2.8%, respectively. The median age at presentation is the seventh decade, and women are given the diagnosis more frequently than men. Unfortunately, most afflicted individuals harbor micrometastatic disease and experience a course characterized by multiple local recurrences before the clinical development of distant disease. Approximately a third of patients have nodal involvement at presentation, and the overall 5-year survival is only 25%. Despite aggressive surgical resection and a multitude of adjuvant treatments, the prognosis remains grave. Early detection, which is difficult because of the occult anatomic locations in which these tumors occur, allows the best hope for cure. PMID- 17349717 TI - The influence of restrained and external eating patterns on overeating. AB - Eating in response to an increasingly obesogenic environment has been strongly implicated as a salient aspect of eating behaviour, arguably influenced by learning and experience. Interindividual differences in susceptibility to weight gain may be due, in part, to variability in response to environmental triggers. The phenomenon of food craving may also be an important factor influencing appetite control. The present study tested a model, in which food craving was hypothesised to be an intervening causal variable, on a causal pathway between responsivity to environmental cues and the development of obesity. One hundred and twenty four participants (aged 21-71 years, 83 females and 41 males) completed the study. Participants completed the Dutch eating behaviour questionnaire (DEBQ), measuring external eating (externality), emotional eating (emotionality) and restrained eating behaviour (restraint), and an adapted form of the food craving inventory (FCI), assessing cravings for carbohydrate, fats, sweets and fast food fats, in addition to total food cravings. Initial analysis showed positive correlations between FCI-tot and body mass index (BMI), FCI-fats and BMI and FCI-fast food fats and BMI in both men and women, and between FCI carbohydrates and BMI in men only. Multiple regression analyses showed externality as the principal predictor of food craving, which was greater in males compared to females, but differential for different food groups between genders. Restrained eating and cravings for fats and fast food fats were negatively associated in women only. As predicted, total cravings, and cravings for fats and fast food foods mediated the positive association between external eating and BMI. It is concluded that appetitive response to external cues as an important risk factor in appetite control is mediated through cravings for particular food groups and is gender-dependent. PMID- 17349718 TI - Dietary restraint: intention versus behavior to restrict food intake. AB - The Dutch Eating Behavior Questionnaire Restraint Scale (DEBQ-R) assesses both intentions to restrict food intake (3 items) and actual behavioral restraint (7 items). Studies in general population's samples have shown that the DEBQ-R is a reliable instrument with all items loading highly on a single factor. The purpose of the present study was to examine the psychometric properties of a two-factor intention-versus-behavior structure of the DEBQ-R in 3 different weight-concerned samples with people from different (over)weight categories (total N=790) using confirmatory factor analysis. A robust two-factor structure emerged in the various samples, generally supporting a distinction between DEBQ-R questions relating to intentions to restrict food intake and actual restrictive behavior. Results obtained in this study are important, because they suggest that a distinction between restrained intention and behavior could help to explain the relation between dietary restraint and external overeating tendencies. Future longitudinal research should examine whether the newly developed dietary restraint scales predict changes in overeating and Body Mass Index (BMI). PMID- 17349719 TI - 3D-QSAR and molecular docking studies on benzothiazole derivatives as Candida albicans N-myristoyltransferase inhibitors. AB - N-Myristoyltransferase has been a promising new target for the design of novel antifungal agents with new mode of action. Molecular docking and three dimensional quantitative structure-activity relationship (3D-QSAR) methods, CoMFA and CoMSIA, were applied to a set of novel benzothiazole Candida albicans N myristoyltransferase (CaNmt) inhibitors. The binding mode of the compounds at the active site of CaNmt was explored using flexible docking method and various hydrophobic and hydrogen-bonding interactions were observed between the benzothiazole inhibitors and the target enzyme. The best CoMFA and CoMSIA models had a cross-validated coefficient q(2) of 0.733 and 0.738, respectively, which showed high correlative and predictive abilities on both the test set and training set. The 3D contour maps of CoMFA and CoMSIA provided smooth and interpretable explanation of the structure-activity relationship for the compounds. The analysis of the 3D contour plots permitted interesting conclusions about the effects of different substituent groups at different position of the benzothiazole ring, which will guide the design of novel CaNmt inhibitors with higher activity. PMID- 17349720 TI - [MPO-ANCA related vasculitis presenting as chronic iron deficiency anemia due to paucisymptomatic intra-alveolar haemorrhage]. AB - INTRODUCTION: An alveolar haemorrhage occurs in 12 to 29% during microscopic polyangeitis and can reveal this disease. EXEGESIS: We report the case of a fifteen years old female patient with a microscopic polyangeitis which was diagnosed during the investigation of a chronic anemia with chronic asymptomatic alveolar haemorrhage and extracapillary glomerulonephritis with antineutrophil cytoplasmic antibodies positive (anti-myeloperoxydase antibodies). The good tolerance of alveolar haemorrhage is usual for children, particularly in idiopathic pulmonary haemorrhage but is exeptionnal for adults. According to some studies, thirty percent of idiopathic pulmonary haemorrhage goes to auto-immune disease. CONCLUSION: This observation shows that complementary pulmonary investigations are necessary in chronic anemia when gynaecologic and digestive investigations are negative and that auto-immune investigations are judicious in the survey of idiopathic pulmonary haemorrhage. PMID- 17349721 TI - [Beta 2-microglobulin amyloidosis presenting as intestinal perforation in a haemodialysis patient]. AB - Long term haemodialysis patient is subject to several complications such as generalised amyloidosis which is the result of deposits of beta2-microglobulin not depurated by haemodialysis. Digestive location causes ischemic accidents such as ulcer, infarctus, digestive haemorrhage, pseudo-obstruction and perforation manifested by a surgical emergency. Our observation is the 6th case of intestinal perforation caused by amyloidosis deposit reported in the literature. PMID- 17349722 TI - [Nodular thrombophlebitis and granulomatous systemic disease]. AB - INTRODUCTION: Nodular thrombophlebitis is septal hypodermitis characterised by vasculitis with vein thrombosis. It may indicate serious underlying disorders. EXEGESIS: We present two cases of nodular superficial phlebitis, which revealed tuberculosis and sarcoidosis. CONCLUSION: Nodular thrombophlebitis are classic during evolution of Behcet disease or Buerger vasculitis. In sarcoidosis, erythema nodosum and granulomatous involvement are the most common cutaneous manifestation. Nodular thrombophlebitis has never been described. Panniculitis are classical in tuberculosis. But most cases are erythema nodosum and cases of erythema induratum of Bazin. Nodular thrombophlebitis could reveal thrombophilic abnormalities, and even more neoplasms especially when they are recurrent and migratory. PMID- 17349723 TI - Intranasal immunization with chlamydial protease-like activity factor and CpG deoxynucleotides enhances protective immunity against genital Chlamydia muridarum infection. AB - We have reported recently that intranasal (i.n.) vaccination with chlamydial protease-like activity factor (CPAF) and interleukin-12 (IL-12) enhances protective immunity against genital chlamydial challenge. In this study, we show that i.n. or intraperitoneal (i.p.) vaccination with CPAF plus CpG deoxynucleotides (CpG), an alternative T helper 1 (Th1) adjuvant, induced robust CPAF-specific IFN-gamma responses and elevated levels of serum antibody and vaginal IgA production. CPAF+CpG vaccinated animals displayed accelerated genital chlamydial clearance, and minimal hydrosalpinx and inflammatory cellular infiltration compared to mock-immunized (PBS) challenged animals. Together, CpG dexoynucleotides are an efficacious alternative Th1 adjuvant with CPAF to induce protective anti-chlamydial immunity. PMID- 17349724 TI - Vaccination with Trypanosoma rangeli reduces the infectiousness of dogs experimentally infected with Trypanosoma cruzi. AB - The goal of this work was to test the efficacy of the vaccination with Trypanosoma rangeli in dogs. Mongrel dogs received three subcutaneous injections of fixed T. rangeli epimastigotes at 6-week intervals. Such immunisation induced antibodies against Trypanosoma cruzi. While both control and immunised dogs developed detectable parasitemia, this was lower and shorter in vaccinated animals. Interestingly, feeding of Triatoma infestans nymphs on vaccinated and chronically infected dogs led to a sharp reduction in the rate of bug infection. These results suggest that it might be possible to reduce the vectorial parasitemia through vaccination of dogs. As dogs are known to play a major role in the domestic cycle of T. cruzi, this might represent a strategy to reduce parasite transmission to humans. PMID- 17349725 TI - Repair of the deep circumflex iliac artery free flap donor site with Protack (titanium spiral tacks) and Prolene (polypropylene) mesh. PMID- 17349726 TI - Re: Wright S, Bekiroglu F, Whear NM, Grew NR. Use of Palacos R-40 with gentamicin to reconstruct temporal defects after maxillofacial reconstructions with temporalis flaps. Br J Oral Maxillofac Surg 2006;44:531-533. PMID- 17349728 TI - A theory of the visual system biology underlying development of spatial frequency lateralization. AB - The spatial frequency hypothesis contends that performance differences between the hemispheres on various visuospatial tasks are attributable to lateralized processing of the spatial frequency content of visual stimuli. Hellige has proposed that such lateralization could arise during infant development from the earlier maturation of the right hemisphere combined with the increasing sensitivity of the visual system to high spatial frequencies. This proposal is intuitively appealing but lacks an explicit theory with respect to the underlying visual system biology. In this paper, we develop such a theory based on knowledge of visual system processing and development. We then translate our theory into a computational model that serves as the basis for a series of development simulations. We find that the simulations produce spatial frequency lateralization effects consistent with those observed empirically. We relate the nature of the neural asymmetry implied by our theory to empirical findings on visual pathway bias and the relative spatial frequency lateralization effect. PMID- 17349729 TI - Intrahippocampal insulin improves memory in a passive-avoidance task in male wistar rats. AB - The main impacts of insulin favor the peripheral organs. Although it functions as a neuropeptide, insulin possesses also some central effects. The aim of this study was to determine the effect of intrahippocampal infusion of insulin on passive avoidance learning in healthy male rats. Thirty male wistar rats were divided into three groups (n=10 each). The experimental group had posttraining insulin infusion into the CA1 region of dorsal hippocampus, after which they were compared with sham (saline) and control (intact) groups. Insulin treated animals had greater latency to enter the dark compartment in compare with saline treated (p=0.023) or control groups (p=0.017). Upon our results, we concluded that intrahippocampal injections of insulin may enhance memory for a simple learning task which supports the concept that insulin possibly plays an endogenous role in memory formation. PMID- 17349730 TI - Mind does really matter: evidence from neuroimaging studies of emotional self regulation, psychotherapy, and placebo effect. AB - This article reviews neuroimaging studies of conscious and voluntary regulation of various emotional states (sexual arousal, sadness, negative emotion). The results of these studies show that metacognition and cognitive recontextualization selectively alters the way the brain processes and reacts to emotional stimuli. Neuroimaging studies of the effect of psychotherapy in patients suffering from diverse forms of psychopathology (obsessive-compulsive disorder, panic disorder, unipolar major depressive disorder, social phobia, spider phobia, borderline personality) are also examined. The results of these studies indicate that the mental functions and processes involved in diverse forms of psychotherapy exert a significant influence on brain activity. Neuroimaging investigations of the placebo effect in healthy individuals (placebo analgesia, psychostimulant expectation) and patients with Parkinson's disease or unipolar major depressive disorder are also reviewed. The results of these investigations demonstrate that beliefs and expectations can markedly modulate neurophysiological and neurochemical activity in brain regions involved in perception, movement, pain, and various aspects of emotion processing. Collectively, the findings of the neuroimaging studies reviewed here strongly support the view that the subjective nature and the intentional content (what they are "about" from a first-person perspective) of mental processes (e.g., thoughts, feelings, beliefs, volition) significantly influence the various levels of brain functioning (e.g., molecular, cellular, neural circuit) and brain plasticity. Furthermore, these findings indicate that mentalistic variables have to be seriously taken into account to reach a correct understanding of the neural bases of behavior in humans. An attempt is made to interpret the results of these neuroimaging studies with a new theoretical framework called the Psychoneural Translation Hypothesis. PMID- 17349731 TI - Using a choice experiment to measure the environmental costs of air pollution impacts in Seoul. AB - Air pollution, a by-product of economic growth, has been incurring extensive environmental costs in Seoul, Korea. Unfortunately, air pollution impacts are not treated as a commercial item, and thus it is difficult to measure the environmental costs arising from air pollution. There is an imminent need to find a way to measure air pollution impacts so that appropriate actions can be taken to control air pollution. Therefore, this study attempts to apply a choice experiment to quantifying the environmental costs of four air pollution impacts (mortality, morbidity, soiling damage, and poor visibility), using a specific case study of Seoul. We consider the trade-offs between price and attributes of air pollution impacts for selecting a preferred alternative and derive the marginal willingness to pay (WTP) estimate for each attribute. According to the results, the households' monthly WTP for a 10% reduction in the concentrations of major pollutants in Seoul was found to be approximately 5494 Korean won (USD 4.6) and the total annual WTP for the entire population of Seoul was about 203.4 billion Korean won (USD 169.5 million). This study is expected to provide policy makers with useful information for evaluating and planning environmental policies relating specifically to air pollution. PMID- 17349732 TI - Removal of copper (II) from aqueous solution by adsorption onto low-cost adsorbents. AB - The use of low-cost adsorbents was investigated as a replacement for current costly methods of removing metals from aqueous solution. Removal of copper (II) from aqueous solution by different adsorbents such as shells of lentil (LS), wheat (WS), and rice (RS) was investigated. The equilibrium adsorption level was determined as a function of the solution pH, temperature, contact time, initial adsorbate concentration and adsorbent doses. Adsorption isotherms of Cu (II) on adsorbents were determined and correlated with common isotherm equations such as Langmuir and Freundlich models. The maximum adsorption capacities for Cu (II) on LS, WS and RS adsorbents at 293, 313 and 333 K temperature were found to be 8.977, 9.510, and 9.588; 7.391, 16.077, and 17.422; 1.854, 2.314, and 2.954 mg g( 1), respectively. The thermodynamic parameters such as free energy (delta G0), enthalpy (delta H0) and entropy changes (delta S0) for the adsorption of Cu (II) were computed to predict the nature of adsorption process. The kinetics and the factors controlling the adsorption process were also studied. Locally available adsorbents were found to be low-cost and promising for the removal of Cu (II) from aqueous solution. PMID- 17349733 TI - Geological and technical characterisation of Iscehisar (Afyon-Turkey) marble deposits and the impact of marble waste on environmental pollution. AB - Turkey, due to its location in the Alpine-Himalayan belt, has numerous marble deposits. More than 250 marble types with different colours and patterns have been produced from these deposits and one hundred of these are well known around the world. One such well-known marble type is Afyon-Iscehisar. Afyon-Iscehisar is Palaeozoic in age and has been quarried since the era of the Roman empire. The Afyon region is known as one of the most important marble production and processing centres in Turkey. The Afyon province, which possesses 3.5% of exploitable marble reserves (3,872,000,000 tonne) in Turkey, yields 9% of the total marble block production. The 409 marble processing plants in Afyon produce 19% of the total slab in Turkey. As a result of marble production activities, approximately 340,000 tonne of marble waste has accumulated in the area. While some of these unshaped marble blocks are re-used and returned to the economy, the majority are discarded. There are two waste marble storage fields located in the Afyon-Iscehisar region. All of the solid and fine-grained marble waste is stored in waste marble storage fields in Susuz Bogazi and in the nearby Iscehisar marble quarries. The ecological effects of the marble waste, which were once discharged everywhere and exhibited visual pollution, has now been reduced to a minimal level. PMID- 17349734 TI - Reconstructive surgery for invasive squamous carcinoma of the glans penis. AB - OBJECTIVES: We present medium-term outcome data for patients with invasive penile cancer treated with glansectomy and reconstruction with a split-thickness skin graft. METHODS: A series of consecutive patients referred with penile malignancies over a 6-yr period were analyzed prospectively. A dedicated histopathologist reviewed all the specimens. After clinical staging, patients with tumours confined to the glans were offered glansectomy. RESULTS: A total of 72 patients (32% of patients, 31% of procedures) underwent glansectomy for penile carcinoma. Of these, 65 patients were new diagnoses and seven were recurrences after radiotherapy. The mean follow-up period was 27 mo (range: 4-68 mo). There have been three late local recurrences (4%). CONCLUSION: Glansectomy appears to be an oncologically safe and effective procedure for patients with glans-confined squamous cell tumours. It preserves maximum phallic length and results in a very satisfactory cosmetic penile appearance after reconstruction. PMID- 17349735 TI - The management of regional lymph nodes in patients with penile carcinoma and reliability of sentinel node biopsy. PMID- 17349736 TI - Editorial comment on: Reconstructive surgery for invasive squamous carcinoma of the glans penis. PMID- 17349737 TI - The gonadotropins: tissue-specific angiogenic factors? AB - The gonadotropins, whose members are human chorionic gonadotropin (hCG), lutenizing hormone (LH) and follicle-stimulating hormone (FSH) are a well characterized hormone family known to regulate reproductive functions in both females and males. Recent studies indicate that they can modulate the vascular system of reproductive organs. It was shown that gonadotropins not only influence the expression of vascular endothelial growth factor (VEGF) and both its receptors VEGFR-1 and -2, but also modulate other ubiquitously expressed angiogenic factors like the angiopoietins and their receptor Tie-2, basic fibroblast growth factor or placental-derived growth factor. Some recent data indicates a possible direct action of gonadotropins on endothelial cells. Thus, the gonadotropins act as tissue-specific angiogenic factors providing an optimal vascular supply during the menstrual cycle and early pregnancy in the female reproductive tract as well as in testis. In pathological conditions (e.g. preeclampsia, intrauterine growth restriction, ovarian hyperstimulation or endometriosis), these tightly regulated interactions between the gonadotropins and the ubiquitous angiogenic factors appear to be disturbed. The intent of this short manuscript is to review the current knowledge of the regulatory role of the gonadotropins in vasculo- and angiogenesis. We also review angiogenic actions of thyroid-stimulating hormone (TSH), a glycoprotein closely related to gonadotropins, which display strong gonodal actions. PMID- 17349738 TI - Guillain-Barre syndrome associated with Salmonella paratyphi A. AB - A 31-year-old Nepali man was admitted to the intensive care unit with a 3-day history of fever associated with four-limb weakness, followed by difficulty in swallowing. The patient came from Nepal 20 days before admission. On examination the patient was conscious and appeared ill, with a temperature of 38.0 degrees C. His four limbs were weak (grades 2-3) and he was areflexic with mild facial weakness and absent gag reflex. Brain CT and MRI were normal. Cerebrospinal fluid analysis showed high protein. A neurophysiologic study showed data consistent with motor axonal polyradiculopathy. The patient was diagnosed with Guillain Barre syndrome (GBS), and intravenous immunoglobulin (0.4 g/kg day for 5 days) was administered. On the third hospitalization day, the patient developed respiratory failure for which he was intubated and mechanically ventilated. On the same day, blood samples grew Salmonella paratyphi A (S. paratyphi A), which was sensitive to ceftriaxone. The patient was then diagnosed with GBS associated with S. paratyphi A, and treated with ceftriaxon (2 g administered intravenously, daily for 10 days). On the eleventh hospitalization day the patient was weaned from ventilator and extubated successfully. Subsequently, the patient improved, his fever subsided, and he regained muscle power satisfactorily. PMID- 17349739 TI - Lumbar subdural haematoma after temporomesial resection in epilepsy patients- report of two cases and review of the literature. AB - We present two cases of lumbar subdural haematoma, both occurring after an uneventful temporomesial focus resection in patients suffering from medically intractable epilepsy. Initial symptom was back pain and sciatica 4 days and 13 days postoperatively, but no neurological deficits were observed. The diagnosis was confirmed by MRI. No risk factor could be identified. The pain responded well to conservative treatment and the haematomas resolved without neurological sequelae. A review of the literature reveals that the characteristics of spinal subdural haematoma following craniotomy are very similar. Six out of 12 reported cases occurred in temporal epilepsy surgery. All had a benign course and did not require an operative procedure. Back pain after epilepsy surgery may be caused by an intraspinal haematoma and should be investigated by MRI. PMID- 17349740 TI - Exploitation of drug-induced Bcl-2 overexpression for restoring normal apoptosis function: a promising new approach to the treatment of multidrug resistant cancer. AB - Agents antagonizing the anti-apoptotic Bcl-2 protein have been shown to restore normal apoptotic processes in cancer cells. Since upregulation of Bcl-2 is often observed in recurrent or refractory hematological malignancies, we were prompted to investigate whether drug-selected leukemia cells overexpressing Bcl-2 were more susceptible to Bcl-2 antagonists. The current study showed that a camptothecin (CPT)-selected human leukemia cell line (CPT-K5) had remarkably higher expression levels of Bcl-2 than its drug sensitive parental cell (RPMI 8402). A small molecule inhibitor of Bcl-2, HA14-1, induced much more extensive apoptosis in CPT-K5 than in RPMI 8402 cells, as characterized by DNA fragmentation, loss of mitochondrial membrane potential (Deltapsi(m)) and plasma membrane integrity, as well as the activation of caspase. Taken together, these findings suggest that small molecule Bcl-2 inhibitors may represent a promising class of alternative agents for the treatment of Bcl-2 overexpressed refractory or recurrent hematological malignancies when conventional chemotherapy fails. PMID- 17349741 TI - Detecting K-ras mutations in stool from fecal occult blood test cards in multiphasic screening for colorectal cancer. AB - Fecal occult blood testing (FOBT) is proven an efficient way of reducing mortality from colorectal cancer but has a relatively low positive predictive value (PPV). This study evaluated the ability to detect K-ras mutations in stool DNA from FOBT cards and to improve the PPV of the screening process. Two hundred and five consecutive positive FOBT cards and an arbitrary sample of 38 negative cards from a population-based screening program were included. K-ras mutations in FOBT card stool were sought using allele-specific hybridization. DNA was successfully amplified from 87.2% of cards. In 130 cases with positive FOBT and amplifiable DNA 23 malignancies and 25 adenomas were detected. In 34.8% of the malignancies, a mutation in K-ras was detected. The PPV for malignancies increased from 17.7% (all positive cards) to 60.0% if cards with four or more fields were positive and K-ras was positive (RR=2.66, 95% CI: 1.2-6.1). Testing for K-ras mutations in DNA extracted from stool from positive FOBT cards is feasible. Sequential detection of cancer-associated genetic markers from FOBT based stool samples may potentially help separate true from false positives in a FOBT-based screening process. PMID- 17349742 TI - Influence of leaks in surface filters on particulate emissions. AB - Compliance with severe limit values of dust emissions is a main characteristic of surface filters. This characteristic is due to the high particle collection efficiency of surface filters. Beside regular operation it is necessary to consider phenomena such as a "pinhole" bypass through leaks in surface filters to ensure the above mentioned compliance with the limit values at all times. Experimental research has been carried out to observe and understand the "pinhole" bypass through leaks and the behaviour of pinholes over filtration time. To work out the influence of different filtration conditions the parameters pinhole diameter, filter face velocity and dust cake thickness were varied. The results can be explained by formulas usually used to calculate volumetric flow rates of orifice gauges. The experiments and the calculations lead to the conclusions that bigger pinholes decrease the collection efficiency and higher filter face velocities increase the collection efficiency of pinholed filter media. PMID- 17349743 TI - Separation technologies for sludge dewatering. AB - Particles in sludge feeds interact strongly one with another to prevent settling and offer a significant resistance to filtration and compression. This leads to the need for dewatering forces to be compressive ones applied directly to the networked solid phase; sometimes shear forces can be an assist dewatering. Designs of filtration equipment most suitable for sludge dewatering have evolved to meet the intrinsic characteristics of sludges, the most important of which are their compressibility and fine particle sizes, which lead to cakes with extraordinarily high solids contents close to the filter medium. Hence, the membrane plate press, the belt filter and the decanter centrifuge have become most widely accepted machines for sludge dewatering. Filter presses tend to yield a drier solids discharge, but the level of dryness depends on the sludge properties. The same feed properties dictate the need for chemical pre-treatment to ensure the highest rates of dewatering and best clarity of filtrate, and correct choice of filter cloth is also crucial in these respects. PMID- 17349744 TI - Adsorption characteristics of Congo Red onto the chitosan/montmorillonite nanocomposite. AB - A series of biopolymer chitosan/montmorillonite (CTS/MMT) nanocomposites were prepared by controlling the molar ratio of chitosan (CTS) and montmorillonite (MMT). The nanocomposites were characterized by FTIR and XRD. The effects of different molar ratios of CTS and MMT, initial pH value of the dye solution and temperature on adsorption capacities of samples for Congo Red (CR) dye have been investigated. The adsorption capacities of CTS, MMT and CTS/MMT nanocomposite with CTS to MMT molar ratio of 5:1 for CR were compared. The results indicated that the adsorption capacity of CTS/MMT nanocomposite was higher than the mean values of those of CTS and MMT. The adsorption kinetics and isotherms were also studied. It was shown that all the sorption processes were better fitted by pseudo-second-order equation and the Langmuir equation. PMID- 17349745 TI - GABA-immunoreactive photoreceptors in the retina of an anuran, Pelobates fuscus. AB - We have recently started to unravel the retinal neurochemistry of an anuran species, the spadefoot toad (Pelobates fuscus), because of its unique lifestyle. The immunolabelling experiments included tests to localize the major inhibitory transmitter, gamma-aminobutyric acid (GABA) to subsets of retinal neurons, using commercially available antibodies. Apart from the regular GABA-immunoreactive pattern observed formerly in other anurans, certain structures in the photoreceptor layer were also regularly labeled for GABA. The soma diameter of the labeled cells is 5-6 microm and the outer segment seems to be unlabeled. In resin-embedded preparations GABA-positive photoreceptor cells were identified as cones based on their sparse distribution and short outer segments. If these cells release GABA as a transmitter, it may act on the second order cells, from which certain horizontal and bipolar cells have functional GABA receptors. Alternatively, GABA may influence the cones themselves through autoreceptors. PMID- 17349746 TI - Trapping efficacy of Duddingtonia flagrans against Haemonchus contortus at temperatures existing at lambing in Australia. AB - The aim of this study was to determine the trapping efficacy of Duddingtonia flagrans against Haemonchus contortus at the temperature ranges experienced around lambing in the major sheep producing regions of Australia. Faeces were collected from Merino wethers, maintained in an animal house and which had received either D. flagrans chlamydospores for a 6-day period (DF) or not (NIL). Faeces were incubated at one of four daily temperature regimens which were composed of hourly steps to provide 6-19 degrees C, 9-25 degrees C, 14-34 degrees C and 14-39 degrees C to mimic normal diurnal air temperature variation. Enumeration of the number of preinfective and infective larvae that had migrated from or remained in faecal pellets was used to calculate percentage recovery and trapping efficacy of D. flagrans. Recovery of H. contortus larvae of both stages was significantly lower in DF faeces but the magnitude of the effect was considerably greater for infective larvae. Mean recovery of infective larvae from NIL and DF faeces was 10.6 and 0.4%, respectively, indicating a mean trapping efficacy of 96.4%. The lowest trapping efficacy (80.7%) was observed at 6-19 degrees C but total recovery of infective larvae, from DF faeces, was greatest at the two highest temperature regimens, although still less than 0.9%. The results of this study indicate that typical Australian lambing temperatures should not be a barrier to the use of D. flagrans as an effective biocontrol of H. contortus in Australia. PMID- 17349747 TI - Spatial distribution of acaricide profiles (Boophilus microplus strains susceptible or resistant to acaricides) in southeastern Mexico. AB - The ability of Boophilus microplus strains to be susceptible (-) or resistant (+) to amidines (Am), synthetic pyrethroids (SP), and/or organo-phosphates (OP) (or acaricide profiles) was investigated in 217 southeastern Mexican cattle ranches (located in the states of Yucatan, Quintana Roo, and Tabasco). Three questions were asked: (1) whether acaricide profiles varied at random and, if not, which one(s) explained more (or less) cases than expected, (2) whether the spatial distribution of acaricide profiles was randomly or non-randomly distributed, and (3) whether acaricide profiles were associated with farm-related covariates (frequency of annual treatments, herd size, and farm size). Three acaricide profiles explained 73.6% of the data, representing at least twice as many cases as expected (P<0.001): (1) Am-SP-, (2) Am+SP+, and (3) (among ranches that dispensed acaricides > or = 6 times/year) Am-OP+SP+. Because ticks collected in Yucatan ranches tended to be susceptible to Am, those of Quintana Roo ranches displayed, predominantly, resistance to OP/SP, and Tabasco ticks tended to be resistant to Am (all with P < or = 0.05), acaricide profiles appeared to be non randomly disseminated over space. Across states, two farm-related covariates were associated with resistance (P < or = 0.02): (1) high annual frequency of acaricide treatments, and (2) large farm size. Findings supported the hypothesis that spatial acaricide profiles followed neither random nor homogeneous data distributions, being partially explained by agent- and/or farm-specific factors. Some profiles could not be explained by these factors. Further spatially explicit studies (addressing host-related factors) are recommended. PMID- 17349748 TI - Sphingosine 1-phosphate stimulation of NADPH oxidase activity: relationship with platelet-derived growth factor receptor and c-Src kinase. AB - This study demonstrates for the first time that sphingosine 1-phosphate (S1P) increases H2O2 production in NIH3T3 fibroblasts through NADPH oxidase activation, confirming the involvement of phosphoinositide-3-kinase and protein kinase C in the activation of this enzyme in non-phagocyte mammalian cells. The results demonstrate also that both platelet-derived growth factor (PDGF) and S1P-mediated NADPH oxidase activation and H2O2 production by Gi-protein coupled receptors (GPCRs) and c-Src kinase. Moreover, both PDGF and S1P activate c-Src kinase through GPCRs, indicating that this kinase can constitute a connection factor between PDGF and S1P signaling, confirming the cross-talk previously found between their receptors. Thus, Gi-protein-mediated NADPH oxidase activation with the consequent H2O2 increase constitutes an early event in the PDGF and S1P pathways. However, a different time course of H2O2 production in S1P-stimulated cells compared to that obtained in PDGF-stimulated cells has been observed, and this seems to be related to the different activation behavior of c-Src kinase induced after S1P or PDGF stimulation. Finally, these data demonstrate that S1P induced H2O2 production is necessary to maximize c-Src kinase activation, confirming that this is a redox regulated kinase. After which, c-Src plays an important role both upstream and downstream from NADPH oxidase activation. PMID- 17349749 TI - Response of the HPA-axis to alcohol and stress as a function of alcohol dependence and family history of alcoholism. AB - Dysfunction of the hypothalamic-pituitary-adrenal (HPA)-axis has been observed in chronic alcoholics and in non-alcoholic sons of alcoholic parents, while genetic and environmental factors, such as stress, may play a significant role in the development of alcoholism. The present study was designed to investigate the response of the HPA-axis to alcohol and stress as a function of family history of alcoholism and chronic alcohol abuse. We determined changes in plasma adrenal corticotrophin (ACTH) and cortisol concentrations in response to a placebo or an alcohol (0.50g ethanol/kg body wt) drink and to a stress task performed 30 min following ingestion of either the placebo or the alcohol drink in social and heavy drinkers with [high risk (HR)] and without [low risk (LR)] a family history of alcoholism. Thus, four groups of healthy male individuals, low risk with no alcohol-dependence diagnosis (LRNAD), high risk with no alcohol-dependence diagnosis (HRNAD), low-risk alcohol dependent (LRAD) and high-risk alcohol dependent (HRAD), participated in the four experimental sessions given in random order. Basal plasma ACTH levels of LRNAD participants were higher from those of the other three groups of participants. Basal plasma cortisol levels of HRAD participants were higher from those of LRNAD and HRNAD but not of LRAD participants. The stress-induced increases of plasma ACTH and cortisol concentrations were more pronounced in LRNAD participants. The alcohol drink prevented the stress-induced increases in plasma ACTH and cortisol of all groups of participants. The self-ratings of anxiety were attenuated in LRNAD and LRAD participants in the alcohol only session and in HRNAD and HRAD participants in the alcohol plus stress session. In conclusion, there are differences in the activity of the HPA-axis as a function of family history and alcohol dependence, while the effect of an alcohol drink on the self-rating of anxiety may be influenced by both family history and stress. PMID- 17349750 TI - Pellagra: A clue as to why energy failure causes diseases? AB - Pellagra is a curable dietary illness that unchecked leads to dementia, diarrhoea, dermatitis and death due to lack of the precursors for NAD(H). In addition it caused a wide range of monosyndromic degenerative and functional neurological disorders as well as profound developmental, premature aging and metabolic syndromes. Pellagrins harbour many chronic infections including tuberculosis, yeasts and malaria, that may be symbionts supplying nicotinamide adenine dinucleotide {NAD(H)} when the diet is poor. Many common diseases and aging may be caused by electrogenic energy mismatches from lack of a timely supply of NAD(H) creating disturbed metabolic fields and "protonopathies". Initially these may present in compartments fronted by homeostatic corrections from chronic symbiotic infections to inflammatory disease, cancer and degenerative/autophagic diseases that can all release NAD(H). PMID- 17349751 TI - Antioxidant activity of Agaricus blazei. AB - The ethanolic extract of Agaricus blazei and ethyl acetate and hydroalcoholic fractions were evaluated for their antioxidant activity. PMID- 17349752 TI - Genetic characterization of maedi-visna virus (MVV) detected in Finland. AB - The aim of the study was to characterize the small-ruminant lentiviruses (SRLVs) detected in Finland by defining their phylogenetic relationships and by studying the evolution of the virus based on a well-known epidemiology. The study material comprised lung tissue samples of 20 sheep from 5 different farms, a cell-cultured virus from one of the original sheep lung samples, and a blood sample of a goat. The sheep were identified as positive during seroepidemiologic screenings in 1994 1996 and the goat in 2001. Initial classification of a 251 nucleotide sequence within gag gene amplified from the uncultured samples as well as from the cell cultured virus showed that the SRLVs were genetically close and that they were more closely related to the prototype ovine maedi-visna viruses (MVVs) than to the caprine arthritis-encephalitis virus (CAEV). The lentivirus detected from the goat aligned within the cluster of the Finnish ovine viruses, demonstrating a natural sheep-to-goat transmission. Further phylogenetic analysis of the proviral gag, pol and env sequences confirmed the initial classification and showed that they constituted a new subtype within the diverse MVV group. The sequence analyses also showed that the virus had remained genetically relatively stable, in spite of the time given for virus evolution, an estimated 20 years, and in spite of the virus crossing the host species barrier. PMID- 17349753 TI - Preparation of an enteric-soluble solid-state emulsion using oily drugs. AB - To improve the patient's compliance and enhance the stability of oily drugs in the gastric fluid, an enteric-soluble solid-state emulsion (ESE), was developed. The ESE was prepared by spreading liquid o/w-emulsions on a flat glass and drying at the oven maintained at 40 degrees C. Aerosil 200 was applied as solid carrier and emulsifier. And Eudragit L30D-55 was used as enteric coating material. The influence of various preparation parameters on the residual volatile oil and the release behavior was investigated. Droplet size distribution of the primary emulsions and the emulsion after reconstitution of zedoary turmeric oil (ZTO) ESE in the phosphate buffer were also measured. When ZTO ESE was immersed into phosphate buffer (pH 6.8), the stable emulsion was formed in 20min, but the release was obviously suppressed when it was exposed to the gastric fluid. It was concluded that preparation of enteric-soluble solid-state emulsion by the present method for oral oily drug was feasible. PMID- 17349754 TI - Study on liposomalization of zinc-coproporphyrin I as a novel drug in photodynamic therapy. AB - Photodynamic therapy (PDT) with a photosensitizer and laser irradiation has been shown to have potential effects in cancer chemotherapy. However, the commercial drug clinically gave many problems due to the poor solubility of the photosensitizer in water and the photosensitivity as an adverse reaction of PDT. We have examined best condition on the liposomalization of Zn-complexed coproporphyrin I (ZnCPI) as novel photosensitizer. The difference of pH in buffer significantly changed the ZnCPI entrapped ratio. The entrapped ratio of ZnCPI in PBS(-) buffer was 10.8+/-0.3%, whereas, these levels in some lactate buffer (below pH 5.0) increased. The change between the molecular form<=>ionic form of ZnCPI was occurred due to the change of the pH of buffer, and the amount of ZnCPI in the liposomal membrane changed. The difference of this level was considered to be contributed by the change of zeta potentials. Next, we examined the effect of the different pH of the buffer in liposomal preparation on the ZnCPI distribution in each tissue after each liposome administration. At 2 and 6h post-injection of ZnCPI liposome (pH 4.6), the ZnCPI concentration in the plasma of Ehrlich ascites carcinoma bearing mice was shown to be higher compared to that in other groups. The ZnCPI concentrations in the tumor after 2 and 6h of ZnCPI liposome (pH 4.6) treatment were shown to be higher than that in other groups. In conclusion, it is considered that the ZnCPI liposome (pH 4.6) had the effective antitumor activity with laser irradiation without the adverse reactions. PMID- 17349756 TI - Anti-inflammatory effect of Sasim extracts in PHA-stimulated THP-1 and peripheral blood mononuclear cells from cerebral infarction patients. AB - Sasim, a prescription composed of seven herbal mixtures, has been widely used for the treatment of cerebral infarction as an oriental medicine in Korea. However, the mechanisms by which the formula affects on the production of pro-inflammatory cytokines in cerebral infarct patients remain unknown yet. The levels of secretory protein and mRNA of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interlukin (IL)-1beta, and IL-6, were significantly increased in both THP-1 differentiated macrophage-like cells (T/M) and peripheral blood mononuclear cells (PBMCs) from cerebral infarct patients at 24h after stimulation with phytohemagglutinin (PHA) (p<0.05). However, pretreatment of Sasim strongly suppressed the secretion of pro-inflammatory cytokines in PHA stimulated T/M cells and PBMCs. Moreover, Sasim significantly suppressed the transcriptional levels of pro-inflammatory cytokines in PHA-stimulated THP-1/M cells. These data indicate that Sasim may be beneficial in the cessation of inflammatory processes of cerebral infarction through suppression on the production of pro-inflammatory cytokines via inhibition of mRNA expression. PMID- 17349757 TI - Allele frequencies for nine STR loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820) in the Italian population. AB - Genotype and allele frequencies for STR loci D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820 were investigated in 289 unrelated Italian Caucasian individuals from the North and South regions. After co-amplification by polymerase chain reaction, automatic DNA profiling of these nine STR loci was performed by ABI PRISM((R)) 310 DNA Genetic Analyzer. For each locus, statistical parameters for forensic and paternity purposes were then calculated; the combined power of discrimination and the combined power of exclusion of all nine loci were 0.9999999999917 and 0.99992 for the Northern population and 0.9999999999921 and 0.99991 for the Southern population. PMID- 17349758 TI - Allelic frequencies of the 15 STR loci included in the AmpFlSTR Identifiler PCR Amplification Kit in an autochthonous sample from Spain. AB - The aim of this study was to estimate the allelic frequencies of the 15 STR loci included in the AmpFlSTR Identifiler PCR Amplification Kit in a sample of 342 unrelated Caucasian individuals autochthonous from Spain to be used for forensic purposes and population studies. The combined power of discrimination and the combined power of exclusion for all of the 15 loci were 5.68x10(-18) and 0.9999964, respectively. According to the obtained data, the D18S51 locus may be considered the most informative among the tested loci. PMID- 17349759 TI - Genetic polymorphisms of 15 AmpFlSTR identifiler loci in Romani population from Northwestern Croatia. AB - The 15 AmpFlSTR identifiler PCR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818 and FGA) were analyzed in the sample of 100 unrelated Romani individuals from Northwestern Croatia. The agreement with HWE was confirmed for all loci. The combined power of discrimination (PD) and the combined power of exclusion (PE) for the 15 studied loci were 0.9999999999999996243580692 and 0.999990752, respectively. According to the presented data, D2S1338 proved to be the most informative marker. Population comparisons revealed significantly different F(ST) values for all analyzed population pairs. PMID- 17349760 TI - [MRI of knee tuberculous arthritis]. AB - Tuberculous arthritis is rare and the diagnosis may be confused with inflammatory arthritis. Only few cases, explored by MRI, have been reported in the literature. We report 3 cases of tuberculous arthritis of the knee revealed by insidious pain. The abnormalities revealed by MRI suggested tuberculosis. Diagnosis was confirmed by histology. PMID- 17349761 TI - Alteration of Drosophila life span using conditional, tissue-specific expression of transgenes triggered by doxycyline or RU486/Mifepristone. AB - The conditional systems Tet-on and Geneswitch were compared and optimized for the tissue-specific expression of transgenes and manipulation of life span in adult Drosophila. Two versions of Tet-on system reverse-tetracycline-Trans-Activator (rtTA) were compared: the original rtTA, and rtTAM2-alt containing mutations designed to optimize regulation and expression. The rtTAM2-alt version gave less leaky expression of target constructs in the absence of doxycyline, however the absolute level of expression that could be achieved was less than that produced by rtTA, in contrast to a previous report. Existing UAS-rtTAM2-alt insertions were re-balanced, and combined with several tissue-general and tissue-specific GAL4 driver lines to yield tissue-specific, doxycyline-inducible transgene expression over three orders of magnitude. The Geneswitch (GS) system also had low background, but the absolute level of expression was low relative to Tet-on. Consequently, actin5C-GS multi-insert chromosomes were generated and higher-level expression was achieved without increased background. Moderate level over expression of MnSOD has beneficial effects on life span. Here high-level over expression of MnSOD was found to have toxic effects. In contrast, motor-neuron specific over-expression of MnSOD had no detectable effect on life span. The results suggest that motor-neuron tissue is not the essential tissue for either MnSOD induced longevity or toxicity in adult males. PMID- 17349762 TI - Overexpression of hUMP1/POMP proteasome accessory protein enhances proteasome mediated antioxidant defence. AB - The proteasome is the major cellular proteolytic machinery. It is involved in the regulation of various pathways via the selective degradation of either short lived normal proteins or damaged proteins permitting the cellular detoxification. Proteasome has impaired function during several biological processes, including aging and diseases; however, it can be activated through overexpression of beta(5)- or beta(1)-subunits, resulting to enhanced survival and extended lifespan. In the current study, we have investigated proteasomal up-regulation via overexpression of hUMP1/POMP protein, the known accessory factor for proteasome assembly in humans. hUMP1/POMP overexpressing fibroblasts have increased levels of functional proteasome and enhanced capacity to cope better and faster with various oxidative stressors. These data highlight hUMP1/POMP role in proteasome assembly and further strengthen the prospect of genetic manipulation of the proteasomal system. PMID- 17349763 TI - Hemodynamics of ovarian veins: MR angiography in women with uterine leiomyomata. AB - PURPOSE: The passive reflux into ovarian veins (OVs) is well known as a common finding in normal asymptomatic women. The purpose of this study was to investigate the hemodynamics of OVs in women with myomatous uterus. MATERIALS AND METHODS: Thirty-two women with symptomatic uterine leiomyomata underwent time-of flight MR (TOF-MR) angiography, including venography and arteriography, and contrast-enhanced MRI. The frequency of reflux into OVs on TOF-MR angiography was retrospectively assessed with uterine volume, and compared to that of normal women in previous publication. The statistical evaluation was performed using Fisher's exact test. RESULTS: The mean uterine volume was 932 +/- 612 ml (range, 301-2627 ml). The reflux into left OVs was observed in 4 of 32 women (13%) and that into right OVs was noted in 0 of 32 women (0%). These rates were significantly lower than those of normal asyptomatic women in the previous publication (p<0.05). The reflux into OVs was observed in 0 of 19 women (0%) with 600 ml or larger myomatous uterus, whereas it was noted in 4 of the remaining 13 women (31%) with less than 600 ml myomatous uterus, with significant difference between the two groups (p=0.02). CONCLUSIONS: We found that reflux into OVs was infrequent in the vast majority of women with myomatous uterus, especially those with larger uterus due to leiomyomata on the basis of TOF-MR angiography. These findings suggested myomatous uterus could affect the flow direction of OVs, and passive reflux into OVs might be prevented due to the influence of antegrade flow of OVs. PMID- 17349764 TI - Sensitive and rapid LC-ESI-MS method for the determination of trimetazidine in human plasma. AB - A sensitive method, based on liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS), was developed for the determination of trimetazidine in human plasma. Buflomedil was used as the internal standard (IS). Plasma samples were extracted with a mixture of cyclohexane-diethyl ether (1:1, v/v) and the analytes were chromatographically separated on a phenomenex Luna 5 mu C18 (2) 100A HPLC column with a mobile phase of 10 mM ammonium acetate buffer solution containing 0.1% acetic acid-methanol (45:55, v/v). The electrospray ionization was employed in a single quadrupole mass spectrometer for the analytical determination. The lower limit of quantification (LLOQ) was 0.5 ng/ml for trimetazidine and the measuring ranges were from 0.5 to 200 ng/ml. The intra- and inter-run standard deviation was less than 4.1% and 7.8%, respectively. The method was successfully applied to study the pharmacokinetics of trimetazidine in healthy Chinese volunteers. PMID- 17349765 TI - High performance liquid chromatographic determination of 3-methylflavone-8 carboxylic acid, the main active metabolite of flavoxate hydrochloride in human urine. AB - High performance liquid chromatographic (HPLC) method was presented for the determination of 3-methylflavone-8-carboxylic acid as the main active metabolite of flavoxate hydrochloride (FX) in human urine. The proposed method was based on using CN column with mobile phase consisting of acetonitrile-12 mM ammonium acetate (40:60, v/v) and adjusted to apparent pH 4.0 with flow rate of 1.5 ml min(-1). Quantitation was achieved with UV detection at 220 nm. The proposed method was utilized to the determination of dissolution rate for tablets containing flavoxate hydrochloride. The urinary excretion pattern has been calculated using the proposed method. PMID- 17349766 TI - Assessment of the solid-state composition of an active salicylanilide compound by FT-Raman spectroscopy. AB - A biologically active salicylanilide compound currently appears in three known solid-state forms: polymorph I (Pol I), polymorph II (Pol II) and the amorphous form (Amorph). The obtained FT-Raman spectra revealed several regions of interest (ROIs) qualitatively distinguishing the different forms, allowing samples with an unknown polymorphic composition to be quantitatively analysed by FT-Raman spectroscopy. The Markov-transformed peak areas of the Raman-bands in the ROIs from the samples were determined and compared with the transformed peak areas obtained for the reference solid-state forms. A constrainted linear regression model estimated the contribution of each reference to the different samples. The applicability of this approach was demonstrated by analysing commercially available batches. PMID- 17349767 TI - Quantitative analysis of sulfur-related metabolites during cadmium stress response in yeast by capillary electrophoresis-mass spectrometry. AB - The objective of this research is to establish an evaluation system of metabolites by capillary electrophoresis-mass spectrometry (CE-MS) in response to chemical stress using the unicellular genome model, yeast (Saccharomyces cerevisiae strain S288C). A method previously reported by Soga et al. was modified and validated for the determination of sulfur-related metabolites, 23 cationic metabolites, in yeast extract. A mixture of 5 mM formic acid in 50% (v/v) 2-propanol was used for the sheath liquid to improve the detection sensitivity. Moreover, washing of CE capillary with 0.1M ammonia solution between successive runs enhanced the reproducibility. After analytical validation, the method was applied to the metabolomic analysis of yeast cells in response to cadmium (Cd) stress. Under Cd exposure, some interesting observations were obtained, particularly the depletion of glycine and the strong accumulation of L gamma-glutamylcysteine in yeast cells. PMID- 17349768 TI - On-line purity monitoring in high-speed counter-current chromatography: application of HSCCC-HPLC-DAD for the preparation of 5-HMF, neomangiferin and mangiferin from Anemarrhena asphodeloides Bunge. AB - An efficient on-line purity monitoring strategy based on on-line coupling of high speed counter-current chromatography (HSCCC) with high-performance liquid chromatography-diode array detection (HPLC-DAD) was successfully applied for the first time to the isolation and purification of 5-hydroxymethyl furancarboxaldehyde (5-HMF), mangiferin and neomangiferin from the Chinese medicinal plant Anemarrhena asphodeloides Bunge, a plant used in the traditional Chinese medicine. The introduction of on-line purity monitoring in HSCCC has greatly improved the efficiency of this technique by overcoming the drawbacks of post-purification sample handling in HSCCC isolation. The effluent from the outlet of HSCCC was split into two parts, and one was collected, while the other was introduced directly through a switch valve into a HPLC-DAD system for purity monitoring. Using this method the desired fractions with high purities could be collected. From 600 mg partially purified extract, 165.6 mg neomangiferin and 292.8 mg mangiferin with purities of 98.9 and 99.5%, respectively, were obtained with a two-phase solvent system composed of n-butanol-water (1:1, v/v) by increasing the flow-rate of the mobile phase stepwise from 1.0 to 2.2 ml min(-1) after 210 min. A 17.1mg 5-HMF with purity of 96.6% was also isolated for the first time. PMID- 17349769 TI - Empowering discourse in patient education. AB - OBJECTIVE: A systematic literature review, using a metasummary technique for qualitative studies (n=15) was conducted to describe the nature of empowering discourses between patient and nurse. METHODS: Computerised searches from 1995 to October 2005 were conducted on the Ovid Medline database using the keywords empower(*), power(*), resource(*), participat(*), facilitat(*), negotiat(*), communicat(*), interact(*), dialog(*), discours(*), discuss(*), encount(*), conversat(*) and 'nurse-patient relations'. All statements concerning empowering discourse were integrated into 29 abstracted findings. Frequency and intensity effect sizes were then calculated. RESULTS: Empowering discourses vary from study to study. Analysed as a whole, an empowering discourse has specific characteristics and structure. Both patients and nurses have essential roles within this type of discourse and their relationship is characterized by an appreciation of each other's expertise within these roles. CONCLUSION: The results of this review show empowerment during discourse between patient and nurse has a complex and multifaceted but analysable nature. More research is needed to find systematic methods of empowering discourse. PRACTICE IMPLICATIONS: The results of this study increase nurses' understanding of empowering methods in patient education identifying ways of facilitating patient empowerment. PMID- 17349770 TI - Physicians do not heal thy relatives. PMID- 17349771 TI - Structural analysis and magnetic resonance imaging predict plaque vulnerability: a study comparing symptomatic and asymptomatic individuals. AB - BACKGROUND: More than half of all cerebral ischemic events are the result of rupture of extracranial plaques. The clinical determination of carotid plaque vulnerability is currently based solely on luminal stenosis; however, it has been increasingly suggested that plaque morphology and biomechanical stress should also be considered. We used finite element analysis based on in vivo magnetic resonance imaging (MRI) to simulate the stress distributions within plaques of asymptomatic and symptomatic individuals. METHODS: Thirty non-consecutive subjects (15 symptomatic and 15 asymptomatic) underwent high-resolution multisequence in vivo MRI of the carotid bifurcation. Stress analysis was performed based on the geometry derived from in vivo MRI of the carotid artery at the point of maximal stenosis. The finite element analysis model considered plaque components to be hyperelastic. The peak stresses within the plaques of symptomatic and asymptomatic individuals were compared. RESULTS: High stress concentrations were found at the shoulder regions of symptomatic plaques, and the maximal stresses predicted in this group were significantly higher than those in the asymptomatic group (508.2 +/- 193.1 vs 269.6 +/- 107.9 kPa; P = .004). CONCLUSIONS: Maximal predicted plaque stresses in symptomatic patients were higher than those predicted in asymptomatic patients by finite element analysis, suggesting the possibility that plaques with higher stresses may be more prone to be symptomatic and rupture. If further validated by large-scale longitudinal studies, biomechanical stress analysis based on high resolution in vivo MRI could potentially act as a useful tool for risk assessment of carotid atheroma. It may help in the identification of patients with asymptomatic carotid atheroma at greatest risk of developing symptoms or mild-to-moderate symptomatic stenoses, which currently fall outside current clinical guidelines for intervention. PMID- 17349772 TI - [Mitochondria in anaesthesia and intensive care]. AB - OBJECTIVE: Mitochondria play a key role in energy metabolism within the cell through the oxidative phosphorylation. They are also involved in many cellular processes like apoptosis, calcium signaling or reactive oxygen species production. The objectives of this review are to understand the interactions between mitochondrial metabolism and anaesthetics or different stress situations observed in ICU and to know the clinical implications. DATA SOURCES: References were obtained from PubMed data bank (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) using the following keywords: mitochondria, anaesthesia, anaesthetics, sepsis, preconditioning, ischaemia, hypoxia. DATA SYNTHESIS: Mitochondria act as a pharmacological target for the anaesthetic agents. The effects can be toxic like in the case of the local anaesthetics-induced myotoxicity. On the other hand, beneficial effects are observed in the anaesthetic-induced myocardial preconditioning. Mitochondrial metabolism could be disturbed in many critical situations (sepsis, chronic hypoxia, ischaemia-reperfusion injury). The study of the underlying mechanisms should allow to propose in the future new specific therapeutics. PMID- 17349773 TI - [Metabolic acidosis in a context of acute severe asthma]. AB - In a context of asthma, lactic acidosis may occur during beta2-agonist therapy. Several cases have been reported during its administration by intravenous and/or inhaled route. This side-effect seems rather unknown and the mechanism for compensation of metabolic acidosis by hyperventilation may worsen dyspnoea and mislead clinicians. Other causes of lactic acidosis such as a major hypoxemia, a cardiovascular collapse or sepsis may also be experienced in this context and must be ruled out before attributing the lactic acidosis to beta2-agonist treatment. We report the case of a 50-year-old man hospitalized for an acute major asthma, who received a salbutamol continuous infusion associated with inhaled terbutaline. A serum lactate level of 13 mmol/l was noted eight hours after the introduction of the bronchodilator treatment. After reducing doses of beta2-agonists, the evolution was favourable, regarding both respiratory and metabolic aspects, with a rapid decrease of the serum lactate level, which finally returned to normal level after 32 hours of hospitalization. PMID- 17349774 TI - Intolerance of uncertainty: Exploring its dimensionality and associations with need for cognitive closure, psychopathology, and personality. AB - The dimensionality and correlates of the Intolerance of Uncertainty Scale (IUS) were examined in a sample of 239 university students. In addition to completing the IUS, participants completed measures of worrying, anxious arousal, anhedonic depression, the big five personality dimensions, and the Need for Closure Scale. A factor analysis of the IUS suggested that it includes the following dimensions: (a) desire for predictability; (b) tendency to become paralyzed in the face of uncertainty; (c) tendency to experience distress in the face of uncertainty; and (d) inflexible uncertainty beliefs. Subscale scores computed on the basis of the factor analysis were differentially associated with the other variables. PMID- 17349775 TI - Emotion regulation and anxiety disorders. AB - Recent attention has been given to the role of emotion regulation in the development and maintenance of psychopathology. Gross [Gross, J. J., & John, O. P. (1998). Mapping the domain of expressivity: multimethod evidence for a hierarchical model. Journal of Personality and Social Psychology, 74, 170-191] provided a framework from which to understand emotion regulation processes, and it is within this framework that the literature on emotion regulation/dysregulation in the anxiety disorder population is reviewed, with a focus on possible deficiencies that lead to or maintain the disorders. The present paper aims to: (1) briefly introduce emotion regulation strategies of suppression and reappraisal; (2) summarize the empirical studies of emotion regulation within anxiety disorders; (3) discuss the neurobiological markers of emotion regulation within these disorders; (4) provide future directions for research; and (5) summarize possible treatment implications resulting from this important area of research. PMID- 17349776 TI - Modulation of microglia and CD8(+) T cell activation during the development of stress-induced herpes simplex virus type-1 encephalitis. AB - The central nervous system (CNS) has been shown to be vulnerable to a variety of insults in animals exposed to glucocorticoids. For example, psychological stress, a known inducer of glucocorticoid production, enhances the susceptibility of mice to herpes simplex virus type-1 (HSV-1) infection and results in the development of HSV-1 encephalitis (HSE). To determine the immune mechanisms by which stress promotes the development of HSE, we examined the role of the glucocorticoid receptor (GR) and the N-methyl-d-aspartate (NMDA) receptor in the development of HSE. Our findings demonstrate that blockade of either the GR or the NMDA receptor enhances survival following HSV-1 infection in stressed mice to levels similar to non-stressed mice. Subsequent studies determined the effect of GR and NMDA receptor blockade on immune function by specifically examining both microglia and CD8(+) T cell activation. Stress inhibited the expression of MHC class I by microglia and other brain-derived antigen presenting cells (CD45(hi)) independent of either the glucocorticoid receptor or the NMDA receptor, suggesting that stress-induced suppression of MHC class I expression in the brain does not affect survival during HSE. Blockade of the NMDA receptor, however, diminished HSV-1 induced increases in class I expression by CD45(hi) cells, suggesting that blockade of the NMDA receptor may limit CNS inflammation. Also, while CD8(+) T cell activation and function in the brain were not affected by stress, the number of CD8(+) T cells in the superficial cervical lymph nodes (SCLN) was decreased in stressed mice via GR-mediated mechanisms. These findings indicate that stress induced hypocellularity is mediated by the GR while NMDA receptor activation is responsible for enhancing CNS inflammation. The combined effects of GR-mediated hypocellularity of the SCLN and NMDA receptor-mediated CNS inflammation during stress promote the development of HSE. PMID- 17349777 TI - Mapping of aggrecan, hyaluronic acid, heparan sulphate proteoglycans and aquaporin 4 in the central nervous system of the mouse. AB - The extracellular matrix (ECM) of the central nervous system (CNS) is found dispersed in the neuropil or forming aggregates around the neurons called perineuronal nets (PNNs). The ECM mainly contains chondroitin sulphate proteoglycans (CSPG), hyaluronic acid (HA) and tenascin-R. Heparan sulphate proteoglycans (HSPG) can also be secreted in the ECM or be part of the cell membrane. The ECM has a heterogeneous distribution which has been linked to several functions, such as specific regional maintenance of hydrodynamic properties in the CNS, in which aquaporins (AQP) play an important role. AQP are a family of membrane proteins which acts as a water channel and AQP4 is the most abundant isoform in the brain. Nevertheless the importance of these proteins, their distribution and correlation in the whole CNS of mice is only partially known. In the present study, the histochemical and immunohistochemical distribution of PNNs, using Wisteria floribunda agglutinin (WFA), aggrecan, HA, HSPGs and AQP4 is described, and their perineuronal and neuropil staining has been semi-quantitatively evaluated in the whole CNS of mice. The results showed that the aggrecan, HA and HSPGs perineuronal distribution coincided partially and this could be related to ECM functional properties. AQP4 showed a heterogeneous distribution throughout the CNS. In some areas, an inverse correlation between AQP4 and ECM components has been observed, suggesting a complementary role for both in the maintenance of water homeostasis. A common location for AQP4 and HSPGs has also been observed in CNS neuropil. PMID- 17349779 TI - Applications of fluorescence microscopy to single bacterial cells. AB - Fluorescence-imaging techniques are now being applied to single bacterial cells for the determination of in vivo kinase and transcription activity, protein protein interactions, protein localization and protein mobility. Time-lapse imaging is being used at a population level to study heterogeneities, colony morphologies and the genetic networks underlying these phenomena. We will discuss here the possibilities, advantages and limitations of such techniques, focusing on the use of green fluorescent protein and its spectral variants. PMID- 17349778 TI - Computer-aided diagnosis in medical imaging: historical review, current status and future potential. AB - Computer-aided diagnosis (CAD) has become one of the major research subjects in medical imaging and diagnostic radiology. In this article, the motivation and philosophy for early development of CAD schemes are presented together with the current status and future potential of CAD in a PACS environment. With CAD, radiologists use the computer output as a "second opinion" and make the final decisions. CAD is a concept established by taking into account equally the roles of physicians and computers, whereas automated computer diagnosis is a concept based on computer algorithms only. With CAD, the performance by computers does not have to be comparable to or better than that by physicians, but needs to be complementary to that by physicians. In fact, a large number of CAD systems have been employed for assisting physicians in the early detection of breast cancers on mammograms. A CAD scheme that makes use of lateral chest images has the potential to improve the overall performance in the detection of lung nodules when combined with another CAD scheme for PA chest images. Because vertebral fractures can be detected reliably by computer on lateral chest radiographs, radiologists' accuracy in the detection of vertebral fractures would be improved by the use of CAD, and thus early diagnosis of osteoporosis would become possible. In MRA, a CAD system has been developed for assisting radiologists in the detection of intracranial aneurysms. On successive bone scan images, a CAD scheme for detection of interval changes has been developed by use of temporal subtraction images. In the future, many CAD schemes could be assembled as packages and implemented as a part of PACS. For example, the package for chest CAD may include the computerized detection of lung nodules, interstitial opacities, cardiomegaly, vertebral fractures, and interval changes in chest radiographs as well as the computerized classification of benign and malignant nodules and the differential diagnosis of interstitial lung diseases. In order to assist in the differential diagnosis, it would be possible to search for and retrieve images (or lesions) with known pathology, which would be very similar to a new unknown case, from PACS when a reliable and useful method has been developed for quantifying the similarity of a pair of images for visual comparison by radiologists. PMID- 17349780 TI - The rrn locus and gyrB genotyping confirm the existence of two clonal groups in strains of Yersinia enterocolitica subspecies palearctica biovar 1A. AB - Eighty-one strains of Yersinia enterocolitica biovar 1A representing several serotypes isolated from India, France, Germany and the USA were analyzed using ribotyping, 16S-23S rDNA intergenic spacer length polymorphism analysis (PCR ribotyping) and gyrB restriction fragment length polymorphism. Ribotyping with BglI, NciI and EcoRV distinguished 81 strains into 4, 3 and 2 ribotypes respectively. BglI-NciI combination gave the highest Simpson's diversity index (DI=0.43). Strains with identical ribotypes were further differentiated by PCR ribotyping. The combination of BglI-NciI ribotyping with PCR ribotyping increased DI to 0.72. This suggested that the combination of the two may be used for molecular epidemiological studies of Y. enterocolitica biovar 1A. This approach clearly resolved the strains into two clonal groups, each comprising strains isolated from humans, swine, pork and wastewater. PCR-RFLP of the gyrB gene using three enzymes (AluI, MspI and HinfI) distinguished strains into seven types and confirmed the existence of two clonal groups. Thus, assessment of heterogeneity based on chromosomal restriction analysis (ribotyping), rRNA spacer length polymorphism (PCR-ribotyping) and gyrB gene analysis were in concordance and provided unequivocal evidence for the presence of two groups amongst strains of Y. enterocolitica biovar 1A despite their diverse geographic origins. These data also grouped clinical and non-clinical strains of serotype O:6,30-6,31 into discrete subgroups. PMID- 17349781 TI - Association between serotonin transporter availability and hostility scores in healthy volunteers - a single photon emission computed tomography study with [(123)I] ADAM. AB - The present study examined the relationship between serotonin transporter (SERT) availability and hostility scores in healthy volunteers. SERT availability was measured by using SPECT with [(123)I] ADAM in 10 healthy participants. Hostility was measured with the Cook-Medley Hostility Scale. Hostile attribution, but not the other subscales of hostility, was negatively correlated with SERT availability. Central serotoninergic activities may play a role in hostility. PMID- 17349782 TI - Antibody-antigenic peptide interactions monitored by SPR and QCM-D. A model for SPR detection of IA-2 autoantibodies in human serum. AB - This work reports on a complementary use of surface plasmon resonance (SPR) and quartz crystal microbalance with dissipation monitoring (QCM-D) technologies to study interactions between a peptide antigen and polyclonal antibodies, in an experimental format suitable for diagnostic assays of autoimmune diseases. In the chosen model, a synthetic peptide from the juxtamembrane region of IA-2 (a type 1 diabetes associated antigen) was immobilized by an optimized chemical protocol applicable to both BIACORE and QCM-D sensors. A thorough study of the peptide immobilization was performed to optimize the signal-to-noise ratio using mixed self-assembled monolayers (SAM) on a gold surface. Introduction of polyethylene glycol (EG(6)) chains into mixed SAM layers and addition of an anionic surfactant to the human serum reduced non-specific binding without modifying the viscoelasticity properties of the layer. Under our conditions, the antibody SPR detection limit was determined to be 0.2 nM in diluted human serum. This value is in agreement with the reported rank distribution of IA-2 antibodies in diabetic patient sera. Label-free and real-time technologies such as SPR and/or QCM-D could be precious tools in future diagnostic assays. PMID- 17349783 TI - Magnetic resonance spectroscopy suggests key differences in the metastatic behaviour of medulloblastoma. AB - BACKGROUND: Metastatic medulloblastoma has a poorer prognosis than localised disease in part due to inherent properties of the tumour. 1H magnetic resonance spectroscopy (MRS) provides a powerful method for investigating tumour metabolism in vivo. METHODS: Magnetic resonance imaging and short echo time (Te 30 ms) single voxel MRS were performed on the primary tumour of 16 children with medulloblastoma prior to surgical resection. Tumour volumes were calculated using a segmentation technique and the MRS was analysed using LCModel. RESULTS: Patients with metastatic disease had primary tumours which were smaller (p=0.01), had higher levels of total choline (p=0.03) and lower levels of mobile lipids (p=0.04). CONCLUSION: Metastatic medulloblastomas have metabolite profiles indicative of increased cell growth and decreased cell death compared with localised tumours reflecting intrinsic differences in underlying biology. Localised tumours with an MRS metabolite profile similar to those with metastatic disease may be at increased risk of metastatic relapse. PMID- 17349784 TI - ECOG performance status 0 or 1 and symptom classification do not improve the ability to predict renal cell carcinoma-specific survival. AB - OBJECTIVES: We tested and compared the improvement in prognostic ability related to the consideration of either ECOG performance status (ECOGPS) and/or symptom classification (S-CLASS) in renal cell carcinoma specific mortality (RCC-SM) predictions. METHODS: Univariate and multivariate Cox regression analyses targeted RCC-SM in 2570 RCC patients treated with either partial or radical nephrectomy. The increment in predictive accuracy related to the addition of either ECOGPS, S-CLASS or both was quantified using Harrell's concordance index. RESULTS: Follow-up ranged from 0.1 to 23 years (median 3.2) and 610 patients (23.7%) died of RCC. In multivariable analyses, ECOGPS and S-CLASS represented independent predictors of RCC-SM. The addition of ECOGPS to established RCC-SM predictors increased the predictive accuracy by 0.3% (p=0.8) versus 0.6% (p=0.5) for S-CLASS versus 0.6% (p=0.5) for both. CONCLUSIONS: Neither ECOGPS nor S-CLASS improves the ability to predict RCC-SM. Therefore, these variables may be safely omitted when RCC-SM risk is quantified. PMID- 17349785 TI - Cancer incidence in AIDS patients in Catalonia, Spain. AB - HIV infected people and AIDS patients develop cancer more frequently than the general population. The objective of this study was to evaluate the risk of developing cancer among 15 to 69 year old AIDS patients from two geographic areas: Tarragona and Girona provinces, in north-eastern Spain. We have studied invasive and in situ cancers (for all sites) among 1659 AIDS patients from +/-5 years around the date of their AIDS diagnosis by matching the population-based Cancer Registries with the AIDS Registry covering these populations. The periods used in the linkage were 1981-1998 for Tarragona and 1994-1999 for Girona. Sex and age-standardised incidence ratios (SIRs) of observed-to-expected cancers were calculated by type of cancer as a measure of risk. For selected types of cancers, SIRs were also calculated for HIV exposure category. Compared with the general population, incidence of cancer among AIDS patients (invasive and in situ) increased 22.9 fold in men (n=142) and 21.0 fold in women (n=45). High statistically significant SIRs were found for Kaposi's sarcoma (KS) (male, 486.4; female, 1030.0), non-Hodgkin's lymphoma (NHL) (male, 126.1; female, 192.8) and invasive cervical cancer (41.8). High risks were also found for Hodgkin's lymphoma (31.1), liver cancer (29.4) and lung cancer (9.4) in men, and in situ cervical cancer (24.4) in women. For all non-AIDS defining malignant neoplasms as a group SIRs were 3.4 in men and 2.5 in women. Among men, homo/bisexuality was strongly related to risk of KS and NHL. The rates of cervical cancer, Hodgkin's lymphoma, liver cancer and lung cancer were among the highest ever reported linked to HIV infection. For the cervical cancer this could be attributable to the low incidence of this cancer in the general population and to the high prevalence of intravenous drug users among HIV women and probably due to poor preventive strategies in this population. PMID- 17349786 TI - Lactate dehydrogenase as a prognostic factor for survival time of terminally ill cancer patients: a preliminary study. AB - This study evaluated lactate dehydrogenase (LDH) as a prognostic factor for survival time in terminal cancer patients. We prospectively followed 93 consecutive inpatients with terminal cancer in one general hospital. Cox's proportional hazard model was used to adjust the influence of some clinical and laboratory variables on survival time. For 25 patients, LDH levels at 2 weeks and 1 week before death were compared by paired t test. In multivariate analysis, elevated LDH level (313 IU/L) was confirmed as an unfavourable indicator for survival time (hazard ratio=2.087, p=0.002). Serum LDH levels were significantly increased as the patients approached death. A combined index comprising LDH levels, C reactive protein levels, uric acid levels, presence of moderate to severe pain, fatigue, hypotension and performance status demonstrated a good stratification value for predicting survival time. Our results showed that serum LDH level can be a useful predictor of survival time of terminally ill cancer patients. PMID- 17349787 TI - Influence of pressure on pyrolysis of black liquor: 2. Char yields and component release. AB - This is the second in a series of papers concerning the behavior of black liquor during pyrolysis at elevated pressures. Two industrial black liquors were pyrolyzed under pressurized conditions in two laboratory-scale devices, a pressurized single-particle reactor and a pressurized grid heater. Temperatures ranging between 650 and 1100 degrees C and pressures in the range 1-20 bar were studied. Char yields were calculated and based on analysis of some of the chars the fate of carbon, sodium, potassium and sulfur was determined as a function of pyrolysis pressure. At temperatures below 800 degrees C little variation in char yield was observed at different pressures. At higher temperatures char yield increased with pressure due to slower decomposition of sodium carbonate. For the same reason, sodium release decreased with pressure. Sulfur release, however, increased with pressure primarily because there was less opportunity for its capture in the less-swollen chars. PMID- 17349788 TI - Characterization of beta-xylosidase enzyme from a Pichia stipitis mutant. AB - beta-Xylosidase production was maximal for the mutant Pichia stipitis NP54376 grown on xylan as the sole carbon source. beta-Xylosidase was purified from culture supernatant by (NH(4))(2)SO(4) precipitation and a hydrophobic interaction chromatography on phenyl sepharose. Optima of pH and temperature were 5.0 and 50 degrees C, respectively. The enzyme was inhibited by 2-mercaptoethanol (100%) and Fe(3+) (80%), and moderately affected by Cu(2+), Ag(+), NH(4)(+) and Mg(2+) and SDS. The purified xylosidase hydrolyzed xylobiose and xylo oligosaccharides and it did not exhibit activity against cellulose, starch, maltose and cellobiose. 2.5 g l(-1) glucose repressed beta-xylosidase activity in the NP54376 strain. The K(m) and V(max) values on p-nitrophenyl-beta xylopyranoside were 1.6 mM and 186 micromol p-nitrophenyl min(-1)mg(-1) protein, respectively. Analysis of the hydrolysis products by HPLC indicated that the major hydrolysis product is xylobiose in all the carbon sources tested. PMID- 17349789 TI - Management of warm-season grass mixtures for biomass production in South Dakota USA. AB - Switchgrass (Panicum virgatum L.), big bluestem (Andropogon gerardii Vitman), and indiangrass (Sorghastrum nutans (L.) Nash) are native warm-season grasses commonly used for pasture, hay, and conservation. More recently switchgrass has also been identified as a potential biomass energy crop, but management of mixtures of these species for biomass is not well documented. Therefore, the objectives of our study were to: (1) determine the effects of harvest timing and N rate on yield and biomass characteristics of established warm-season grass stands containing a mixture of switchgrass, big bluestem, and indiangrass, and (2) evaluate the impact of harvest management on species composition. Five N rates (0, 56, 112, and 224 kg ha(-1) applied annually in spring and 224 kg ha(-1) evenly split between spring and fall) and two harvest timings (anthesis and killing frost) were applied to plots at two South Dakota USA locations from 2001 to 2003. Harvesting once a year shortly after a killing frost produced the greatest yields with high concentrations of neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin (ADL) along with lower concentrations of total nitrogen (TN) and ash. This harvest timing also allowed for the greatest percentage of desirable species while maintaining low grass weed percentages. While N rates of 56 and 112 kg ha(-1) tended to increase total biomass without promoting severe invasion of grass and broadleaf weed species, N application did not always result in significant increases in biomass production. Based on these results, mixtures of switchgrass and big bluestem were well suited for sustainable biomass energy production. Furthermore, N requirements of these mixtures were relatively low thus reducing production input costs. PMID- 17349790 TI - Influence of pressure on pyrolysis of black liquor: 1. Swelling. AB - This is the first of two papers concerning the behavior of black liquor during pyrolysis under pressurized conditions. Two industrial kraft liquors were pyrolyzed in a laboratory-scale pressurized single particle reactor and a pressurized grid heater at temperatures ranging from 650 to 1100 degrees C and at pressures between 1 and 20 bar. The dimensions of the chars produced were measured and the specific swollen volume was calculated. Swelling decreased roughly logarithmically over the pressure range 1-20 r. An expression is developed to predict the specific swollen volume at elevated pressure when the volume at 1 bar is known. The bulk density of the char increased with pressure, indicating that liquors will be entrained less easily at higher pressures. PMID- 17349791 TI - Sororin is required for stable binding of cohesin to chromatin and for sister chromatid cohesion in interphase. AB - Sister chromatid cohesion depends on cohesin [1-3]. Cohesin associates with chromatin dynamically throughout interphase [4]. During DNA replication, cohesin establishes cohesion [5], and this process coincides with the generation of a cohesin subpopulation that is more stably bound to chromatin [4]. In mitosis, cohesin is removed from chromosomes, enabling sister chromatid separation [6]. How cohesin associates with chromatin and establishes cohesion is poorly understood. By searching for proteins that are associated with chromatin-bound cohesin, we have identified sororin, a protein that was known to be required for cohesion [7]. To obtain further insight into sororin's function, we have addressed when during the cell cycle sororin is required for cohesion. We show that sororin is dispensable for the association of cohesin with chromatin but that sororin is essential for proper cohesion during G2 phase. Like cohesin, sororin is also needed for efficient repair of DNA double-strand breaks in G2. Finally, sororin is required for the presence of normal amounts of the stably chromatin-bound cohesin population in G2. Our data indicate that sororin interacts with chromatin-bound cohesin and functions during the establishment or maintenance of cohesion in S or G2 phase, respectively. PMID- 17349792 TI - Contending with transcriptional arrest during RNAPII transcript elongation. AB - Studies of RNA polymerase II (RNAPII) transcript elongation have revealed an extremely complex biochemical process. Obstacles to transcription, such as nucleosomes and DNA damage, must be overcome constantly, requiring the involvement of numerous accessory factors with diverse functions. Together, these factors ensure that transcript elongation is, overall, a highly efficient reaction. The understanding of the basic biochemical principles and factors underlying transcript elongation by RNAPII has greatly improved over the past few years. In particular, studies of RNAPII ubiquitylation and degradation have provided new insight into how cells handle obstacle-induced transcriptional arrest. PMID- 17349793 TI - Synthesis and evaluation of 2-(2,6-dihalophenyl)-3-pyrimidinyl-1,3-thiazolidin-4 one analogues as anti-HIV-1 agents. AB - A series of 2-(2,6-dihalophenyl)-3-(substituted pyrimidinyl)-1,3-thiazolidin-4 ones were designed on the prediction of quantitative structure-activity relationship (QSAR) studies, synthesized, and evaluated as HIV-1 reverse transcriptase inhibitors. Our attempts in correlating the identified molecular surface features related properties for modeling the HIV-1 RT inhibitory activity resulted in some statistically significant QSAR models with good predictive ability. The results showed that compounds 4m and 4n were highly active in inhibiting HIV-1 replication with EC(50) values in the range of 22-28 nM in MT-4 as well as in CEM cells with selectivity indexes of >10,000. The derived models collectively suggest that the compounds should be compact without bulky substitution on its peripheries for better HIV-1 RT inhibitory activity. These models also indicate a preference for hydrophobic compounds to obtain good HIV-1 RT inhibitory activity. PMID- 17349794 TI - Amphiphilic polyether branched molecules to increase the circulation time of cationic particles. AB - The preparation, physicochemical and biological properties of amphiphilic polyether branched molecules is described. These 'bunch shaped' molecules when inserted into cationic liposomes/DNA complexes have shown efficient surface charge shielding. As a consequence they efficiently inhibited the non specific interactions with blood components and significantly enhanced circulation time of the particles in the blood track. Formulations containing these molecules compared positively with those containing PEG lipids, providing a 5-fold increase in circulation time. PMID- 17349795 TI - Alarm criteria in radiation portal monitoring. AB - Gamma detectors at border crossings are intended to detect illicit nuclear material. These detectors collect counts that are used to determine whether to trigger an alarm. Several candidate alarm rules are evaluated, with attention to background suppression caused by the vehicle. Because the count criterion leads to many nuisance alarms and because background suppression by the vehicle is smaller for ratios of counts, analysis of a ratio criterion is included. Detection probability results that consider the effects of 5 factors are given for 2 signal-injection studies, 1 for counts, and 1 for count ratios. PMID- 17349796 TI - Behavior of oxidation in the radiochromic gel dosimeter through photoacoustic technique measurements. AB - Natural oxidation is an undesirable process suffered by gel dosimetry systems as it changes the values and spatial distribution of absorbed doses. Natural oxidation of Fricke xylenol gel (FXG) dosimeter was inferred from optical absorbance values measured for the first time using the photoacoustic technique. An acoustic detector measures the intensity of the light transmitted by the FXG, which is directly proportional to the ionizing radiation dose absorbed by the samples. In this work, we demonstrated the behavior, the rates, and the dependence of natural oxidation on storage temperature, time, and active components through measurements by photoacoustic technique. PMID- 17349797 TI - Less fat with nesfatin. AB - The brain receives information on the body's fuel supply through a bewildering array of chemical messengers that signal either negative or positive energy balance. Nesfatin-1, a secreted protein of previously unknown function, acts as a satiety factor. Nesfatin-1 suppresses appetite in both the short term and the long term, is made by neurons in brain centers that regulate energy balance and might act via melanocortin pathways. Nesfatin-1 is the latest addition to the surprisingly large number of chemical messengers telling the body that the tank is full. PMID- 17349798 TI - Doping with growth hormone/IGF-1, anabolic steroids or erythropoietin: is there a cancer risk? AB - Anabolic steroid and peptide hormones or growth factors are utilized to increase the performance of athletes of professional or amateur sports. Despite their well documented adverse effects, the use of some of these agents has significantly grown and has been extended also to non-athletes with the aim to improve appearance or to counteract ageing. Pre-clinical studies and epidemiological observations in patients with an excess of hormone production or in patients chronically treated with hormones/growth factors for various pathologies have warned about the potential risk of cancer development and progression which may be also associated to the use of certain doping agents. Anabolic steroids have been described to provoke liver tumours; growth hormone or high levels of its mediator insulin-like growth factor-1 (IGF-1) have been associated with colon, breast, and prostate cancers. Actually, IGF-1 promotes cell cycle progression and inhibits apoptosis either by triggering other growth factors or by interacting with pathways which have an established role in carcinogenesis and cancer promotion. More recently, the finding that erythropoietin (Epo) may promote angiogenesis and inhibit apoptosis or modulate chemo- or radiosensitivity in cancer cells expressing the Epo receptor, raised the concern that the use of recombinant Epo to increase tissue oxygenation might favour tumour survival and aggressiveness. Cancer risk associated to doping might be higher than that of patients using hormones/growth factors as replacement therapy, since enormous doses are taken by the athletes often for a long period of time. Moreover, these substances are often used in combination with other licit or illicit drugs and this renders almost unpredictable all the possible adverse effects including cancer. Anyway, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer. PMID- 17349799 TI - Protective effect of PNQX on motor units and muscle property after sciatic nerve crush in neonatal rats. AB - Sciatic nerve injury in neonatal rats results in significant reduction in the number of surviving motoneurons and impairs muscle development. We examined the possible neuroprotective effects of daily in vivo administration of 1,4,7,8,9,10 hexahydro-9-methyl-6-nitropyrido[3,4-f]quinoxaline-2,3-dione (PNQX), an AMPA/kainate receptor antagonist, on sciatic nerve injured rats, during the period of plasticity of the rat nervous system. Furthermore, we investigated the effect of PNQX on muscle properties impaired by nerve crush. At the second postnatal day, the sciatic nerve of the rat left hind limb was crushed. Twenty four rats were subsequently treated with PNQX and an equal number of rats, as control group, were treated with saline. PNQX was injected subcutaneously once daily (14 mg kg(-1) body weight). Treatment continued until the rats were 14 days old. Measurements were then carried out to assess the contractile properties of the extensor digitorum longus (EDL), a fast-contracting muscle, and of the soleus muscle, a slow-contracting muscle, in four "age groups" of rats, each consisting of six PNQX-treated and six control animals: (a) postnatal day (P) 14, (b) postnatal day (P) 21, (c) postnatal day (P) 28 and (d) adult rats. The following parameters were recorded: number of motor units, muscle weight, maximal tetanic tension (TET 100), time to peak (TTP), half relaxation time (HRT), and fatigue index (FI). Improvement in motor unit survival after nerve injury was observed in all age groups administering PNQX. Also axotomy-induced impairment of muscle properties such as muscle weight, tension development, contraction and relaxation velocity was counteracted by injection of PNQX. The fatigue index was altered by axotomy and mostly normalized by treatment with this compound. AMPA/kainate receptor antagonists, with low toxicity, may serve in the future, as possible neuroprotective agents after acute neural injury or even as therapeutic agents in neurodegenerative diseases. PMID- 17349800 TI - Carotenoids and human health. AB - Oxidative stress is an important contributor to the risk of chronic diseases. Dietary guidelines recommend increased consumption of fruits and vegetables to combat the incidence of human diseases such as cancer, cardiovascular disease, osteoporosis and diabetes. Fruits and vegetables are good sources of antioxidant phytochemicals that mitigate the damaging effect of oxidative stress. Carotenoids are a group of phytochemicals that are responsible for different colors of the foods. They are recognized as playing an important role in the prevention of human diseases and maintaining good health. In addition to being potent antioxidants some carotenoids also contribute to dietary vitamin A. There is scientific evidence in support of the beneficial role of phytochemicals in the prevention of several chronic diseases. Although the chemistry of carotenoids has been studied extensively, their bioavailability, metabolism and biological functions are only now beginning to be investigated. Recent interest in carotenoids has focused on the role of lycopene in human health. Unlike some other carotenoids, lycopene does not have pro-vitamin A properties. Because of the unsaturated nature of lycopene it is considered to be a potent antioxidant and a singlet oxygen quencher. This article will review carotenoids in general and lycopene in particular for their role in human health. PMID- 17349801 TI - Detection of protein-RNA crosslinks by NanoLC-ESI-MS/MS using precursor ion scanning and multiple reaction monitoring (MRM) experiments. AB - Protein-RNA interactions within ribonucleoprotein particles (RNPs) can be investigated by UV-induced crosslinking of proteins to their cognate RNAs and subsequent isolation and mass-spectrometric analysis of crosslinked peptide-RNA oligonucleotides. Because of the low crosslinking yield, a major challenge in protein-RNA UV crosslinking is the detection of the crosslinked species over the excess of non-crosslinked material, especially when complex systems (native RNPs) are investigated. Here, we applied a novel approach that uses on-line nanoLC-ESI MS/MS to detect and subsequently sequence peptide-RNA oligonucleotide crosslinks from crude mixtures. To detect the crosslinks we made use of features shared by crosslinks and phosphopeptides, that is, the phosphate groups that both carry. A precursor ion scan for m/z 79 (negative-ion mode, -ve) is applied to selectively detect analytes bearing the phosphate-containing species (i.e., residual non crosslinked RNA and peptide-RNA crosslinks) from crude mixtures and to determine their exact m/z values. On this basis, a multiple reaction monitoring (MRM) experiment monitors the expected decomposition from the different precursor charge states of the putative crosslinks to one of the four possible RNA nucleobases [m/z 112, 113, 136, 152 (positive-ion mode, +ve)]. On detection, a high-quality MS/MS is triggered to establish the structure of the crosslink. In a feasibility study, we detected and subsequently sequenced peptide-RNA crosslinks obtained by UV-irradiation of (1) native U1 snRNPs and (2) [15.5K-61K-U4atac] snRNPs prepared by reconstitution in vitro. MRM-triggered collision-induced dissociation (CID) MS/MS enabled us to obtain sequence information about the crosslinked peptide and RNA moiety. PMID- 17349802 TI - Transmission mode ion/ion proton transfer reactions in a linear ion trap. AB - A new method is described for effecting ion/ion proton transfer reactions that involves storage of analyte ions while oppositely charged ions are transmitted through the stored ion population. In this approach, the products are captured and stored in the linear ion trap for subsequent mass analysis. Charge reduction of multiply charged protein ions is used as an example to illustrate the analytical usefulness of this method. In another variation of the transmission mode ion/ion reaction approach, two charge inversion experiments, implemented by passing analyte ions through a population of multiply charged reagent ions in a LIT, are also demonstrated. A pulsed dual ion source approach coupled with a hybrid triple quadrupole/linear ion trap instrument was used to demonstrate these two methods. The results for ion/ion reactions implemented using these so-called "transmission mode" experiments were comparable to those acquired using the more conventional mutual storage mode, both in terms of efficiency and information content of the spectra. An advantage of transmission mode experiments compared with mutual storage mode experiments is that they do not require any specialized measures to be taken to enable the simultaneous storage of oppositely charged ions. PMID- 17349803 TI - Three-dimensional reconstruction of bovine brain V-ATPase by cryo-electron microscopy and single particle analysis. AB - Bovine V-ATPase from brain clathrin-coated vesicles was investigated by cryo electron microscopy and single particle analysis. Our studies revealed great flexibility of the central linker region connecting V1 and V0. As a consequence, the two sub-complexes were processed separately and the resulting volumes were merged computationally. We present the first three-dimensional (3D) map of a V ATPase obtained from cryo-electron micrographs. The overall resolution was estimated 34A by Fourier shell correlation (0.5 cutoff). Our 3D reconstruction shows a large peripheral stalk and a smaller, isolated peripheral density, suggesting a second, less well-resolved peripheral connection. The 3D map reveals new features of the large peripheral stator and of the collar-like density attached to the membrane domain. Our analyses of the membrane domain indicate the presence of six proteolipid subunits. In addition, we could localize the V0 subunit a flanking the large peripheral stalk. PMID- 17349804 TI - Effect of sex-steroid hormones, testosterone and estradiol, on humoral immune parameters of gilthead seabream. AB - The role of sex-steroid hormones, testosterone (T) and 17beta-estradiol (E2), on the humoral immune parameters of the teleost gilthead seabream Sparus aurata was studied attempting to deepen on the knowledge of the immune-reproductive system interactions. Fish were injected intraperitoneally with coconut oil containing different dosages of T (0, 2, or 5 microg g(-1) body weight [bw]) or E2 (0, 1, or 2 microg g(-1) bw) and sampled 1, 3, and 7 days later. Hormonal levels and immune parameters (complement, peroxidase and antiprotease activities and IgM levels) were determined in plasma. Plasma hormone levels peaked at 1 day post-injection decreasing thereafter. Treatment with T significantly increased both complement and peroxidase activities after 3 days of injection but antiprotease activity and IgM levels remained unchanged. Treatment with E2 enhanced complement activity 1 day post-injection while decreased it after 3 and 7 days. However, peroxidase activity increased at 3 and 7 days post-injection while total IgM levels decreased. Implications of T and E2 in the immune-reproductive system interactions were discussed. PMID- 17349805 TI - Context-specific learning and control: the roles of awareness, task relevance, and relative salience. AB - The processes mediating dynamic and flexible responding to rapidly changing task environments are not well understood. In the present research we employ a Stroop procedure to clarify the contribution of context-sensitive control processes to online performance. In prior work Stroop interference varied as a function of probe location context, with larger Stroop interference occurring for contexts associated with a high proportion of congruent items [Crump, M. J., Gong, Z., & Milliken, B. (2006). The context-specific proportion congruent stroop effect: location as a contextual cue. Psychonomic Bulletin &Review, 13, 316-321.] Here, we demonstrate that this effect does not depend on awareness of the context manipulation, but that it can depend on attention to the predictive context dimension, and on the relative salience of the target and predictive context dimensions. We discuss the implications of our results for current theories of cognitive control. PMID- 17349806 TI - Effect of reduced levels of the LDL receptor of Ehrlich ascites tumor cells on cholesterol uptake and cell proliferation: a coculture study with baby hamster kidney cells. AB - We have introduced a heterologous coculture model between Ehrlich ascites tumor (EAT) and baby hamster kidney cells (PtK2), and we have studied the influence of PtK2 cells and their newly synthesized cholesterol on uptake and tumor cell proliferation. PtK2 cells produce about five times more cholesterol as compared to EAT cells, and they support tumor cell growth in coculture experiments. This growth stimulation is reduced by 80% when EAT cells are cultured in PtK2 cell derived medium in the presence of a monoclonal anti-low-density lipoprotein receptor (anti-LDL(r)) antibody. Freshly synthesized cholesterol by PtK2 cells is taken up by EAT cells in a time-dependent manner amounting to a threefold increase after 24 h. Alternatively, cholesterol transfer to EAT cells is decreased between 28% and 35%, when PtK2 cell cholesterol synthesis is inhibited in the presence of mevinolin, the specific inhibitor of the hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase. Furthermore, lower levels of EAT cell LDL receptor induced by antisense technology reduces cholesterol uptake and cell proliferation. These data demonstrate a metabolic interaction between normal and tumor cells mediated via the exchange of cholesterol, an important membrane constituent. PMID- 17349807 TI - Prevalence of Neospora caninum and bovine viral diarrhoea virus in dairy cows in Southern Vietnam. AB - The main purpose of this study was to investigate the prevalence of Neospora caninum and bovine viral diarrhoea virus (BVDV) in some dairy herds in Southern Vietnam, and to ascertain whether there were differences in seroprevalences between herds with imported and locally bred cows. Serum samples collected on five state farms and 97 smallholder herds were analysed for the presence of antibodies to N. caninum and BVDV. All BVDV antibody-negative sera were further tested by antigen-ELISA in order to identify persistently infected individuals. The N. caninum prevalence varied between 16% and 53% in the state herds, and was higher in the four herds that had imported cows than in the herd that only had locally bred cows. Nineteen percent of the samples collected on smallholder farms, which all had only locally bred cows, had antibodies to N. caninum. The BVDV seroprevalence varied between 58% and 93% on the state farms. In smallholder herds, the prevalence of BVDV among the sampled cows was 18% and even lower on the state farms. Despite the high seroprevalence for BVDV in the state herds, no persistently BVDV infected cows were found. Given the high prevalence for Neospora and BVDV among herds with imported cows, it seems advisable to test for both infections before cattle are imported into the country. PMID- 17349808 TI - Structural and chemical basis for enhanced affinity and potency for a large series of estrogen receptor ligands: 2D and 3D QSAR studies. AB - The estrogen receptor (ER) is an important drug target for the development of novel therapeutic agents for the treatment of breast cancer. Progress towards the design of more potent and selective ER modulators requires the optimization of multiple ligand-receptor interactions. Comparative molecular field analyses (CoMFA) and hologram quantitative structure-activity relationships (HQSAR) were conducted on a large set of ERalpha modulators. Two training sets containing either 127 or 69 compounds were used to generate QSAR models for in vitro binding affinity and potency, respectively. Significant correlation coefficients (affinity models, CoMFA, r(2)=0.93 and q(2)=0.79; HQSAR, r(2)=0.92 and q(2)=0.71; potency models, CoMFA, r(2)=0.94 and q(2)=0.72; HQSAR, r(2)=0.92 and q(2)=0.74) were obtained, indicating the potential of the models for untested compounds. The generated models were validated using external test sets, and the predicted values were in good agreement with the experimental results. The final QSAR models as well as the information gathered from 3D contour maps should be useful for the design of novel ERalpha modulators having improved affinity and potency. PMID- 17349809 TI - One-year post-primary antibody persistence and booster immune response to a fully liquid five-component acellular pertussis, diphtheria, tetanus, inactivated poliomyelitis, Haemophilus influenzae type b conjugate vaccine. AB - OBJECTIVE: To evaluate antibody persistence one year after three-dose primary vaccination and booster immune response during the second year of life for a fully liquid diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis Haemophilus influenzae type b (DTaP-IPV-PRP approximately T) vaccine. METHODS: Infants at 18-19 months of age were given a booster dose of either DTaP-IPV-PRP approximately T (group A) or DTaP-IPV plus PRP approximately T at separate injection sites (group B), after primary vaccination at two, four and six months of age, with the same vaccines. Antibody concentrations were measured pre- and post-booster. Reactogenicity and safety were evaluated from parent reports. RESULTS: Before the booster dose, 93.1% of group A and 95.1% of group B children still had anti-PRP antibody titers > or =0.15 microg/ml. All children had antibody levels believed to protect against tetanus, polio 1 (except one subject in group B), polio 2, polio 3, and diphtheria (except one subject in group A). At least 94% of children still had antibody concentrations > or =5 ELISA units (EU) to pertussis antigens (pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), fimbriae 2 and 3 (FIM2+3)). One month after the booster dose, all subjects achieved antibody concentrations or titers believed to be protective for PRP (polyribose ribitol phosphate)(> or =1 microg/ml), diphtheria and tetanus (> or =0.1 IU/ml) and poliovirus types 1, 2, and 3 (> or =81/dil.), and at least 90.5% of subjects had four-fold increases in antibody concentrations to pertussis antigens following the booster. Anti-PRP geometric mean titers (GMTs) increased from 1.07 to 59.6 microg/ml and from 1.8 to 62.2 microg/ml in groups A and B, respectively. Both vaccine groups showed low reactogenicity rates. CONCLUSIONS: The fully liquid pentavalent DTaP-IPV-PRP approximately T vaccine is highly immunogenic, with good antibody persistence for each antigen approximately one year after primary vaccination and strong booster responses at 18-19 months of age. Because this combined vaccine is fully liquid, requiring no reconstitution of lyophilized PRP approximately T, the ease of use and proper administration are improved. PMID- 17349810 TI - GBV-B as a pleiotropic virus: distribution of GBV-B in extrahepatic tissues in vivo. AB - GB virus B (GBV-B) infection of New World monkeys is considered to be a useful surrogate model for hepatitis C virus (HCV) infection. GBV-B replicates in the liver and induces acute resolving hepatitis but little is known whether the other organs could be permissive for the virus. We investigated the viral tropism of GBV-B in tamarins in the acute stage of viral infection and found that the viral genomic RNA could be detected in a variety of tissues. Notably, a GBV-B-infected tamarin with marked acute viremia scarcely showed a sign of hepatitis, due to preferential infection in lymphoid tissues such as lymph nodes and spleen. These results indicate that GBV-B as well as HCV is a pleiotropic virus in vivo. PMID- 17349811 TI - [For a systematic use of perineal prosthesis?]. PMID- 17349812 TI - [Restrictive indications for vaginal meshes]. PMID- 17349813 TI - Non-motor dysfunction in Parkinson's disease. AB - In the field of neurology, Parkinson's disease (PD) is commonly perceived to be a disorder affecting only the (extrapyramidal) motor system, characteristically manifesting as bradykinesia, rigidity, tremor and postural instability. Although non-motor symptoms such as behavioural abnormalities, dysautonomia, sleep disturbances and sensory dysfunctions are also common and quite disabling manifestations of the disease, they are often not formally assessed and thus are frequently misdiagnosed and/or under diagnosed. For this reason, in this review we have concentrated on the pathophysiological and clinical basis of non-motor involvement such as olfactory dysfunction, depression, dementia, dysautonomia and sleep disorders in PD. The early recognition of these symptoms may well perhaps lead to an earlier diagnosis of PD, but in any case should lead to more prompt and effective treatment of the relatively unrecognized non-motor problems associated with PD. PMID- 17349814 TI - The role of cytokines in the regulation of ocular autoimmune inflammation. AB - The eye is a unique place for the development of an immune response. Beyond the usual mechanisms of immune restraint, the eye evolved with its exclusive mechanisms such as anterior chamber associated immune deviation. Therefore, immune-mediated inflammation in the eye does not develop at the same pace as in other sites of the body. Here we will address such peculiarities as they regard to ocular autoimmunity, using the experimental autoimmune uveitis as a model to understand the participation of cytokines in the process of aggression against the eye, as well as their immunoregulatory role. PMID- 17349815 TI - Dynamic kinetic resolution catalyzed by enzymes and metals. AB - The development of new strategies to efficiently synthesize chiral compounds is of extreme importance. Dynamic kinetic resolution is a powerful tool to transform a racemic mixture into one enantiomer. This strategy overcomes the limitation of the maximum 50% yield in a kinetic resolution by combining it with an in situ racemization of the substrate. Recently, the coupling of enzymes and transition metals for dynamic kinetic resolution of a variety of molecules has attracted considerable attention and a deeper understanding of the compatibility of these two catalysts has been achieved. PMID- 17349816 TI - Adding handles to unhandy substrates: anaerobic hydrocarbon activation mechanisms. AB - In spite of their chemical inertness, hydrocarbons are degraded by microorganisms in the complete absence of oxygen. As all known aerobic hydrocarbon degradation pathways start with oxygen-dependent reactions, hydrocarbon catabolism in anaerobes must be initiated by novel biochemical reactions. In recent years, the enzymes catalyzing oxygen-independent activation of several hydrocarbons have been identified. Surprisingly, a variety of reactions seems to be employed to overcome the activation barrier of different hydrocarbons. This review presents the current understanding on some of these reactions and the associated degradation pathways: oxygen-independent hydroxylation as employed in ethylbenzene metabolism, fumarate addition to methyl or methylene carbons in toluene or alkane degradation, and only recently discovered reactions such as methylation of naphthalene or anaerobic methane oxidation via reverse methanogenesis. PMID- 17349817 TI - Theoretical bioinorganic chemistry: the electronic structure makes a difference. AB - Theoretical bioinorganic and biomimetic chemistry involves the careful description of the electronic structure: for example, 'valence bond reading' of broken-symmetry density functional theory computations gives insight into the structure and bonding of metal-radical systems with complex electronic structures. Exploring the reactivities of such systems leads to the design of novel compounds with better reactivities. Combined quantum-mechanics/molecular mechanics (QM/MM), where the QM part is a sophisticated ab initio method, aids in understanding nature's most complicated reaction mechanisms in atomic detail. First principles molecular dynamics simulations (Car-Parrinello simulations) open up exciting new avenues for studying transition metal centers and enable several questions to be addressed that cannot be resolved with either standard quantum chemical or traditional force-field methods. PMID- 17349819 TI - Plant non-specific lipid transfer proteins: an interface between plant defence and human allergy. AB - Plant non-specific LTPs (lipid transfer proteins) form a protein family of basic polypeptides of 9 kDa ubiquitously distributed throughout the plant kingdom. The members of this family are located extracellularly, usually associated with plant cell walls, and possess a broad lipid-binding specificity closely related to their three-dimensional structure. The nsLTP fold is characterized by a compact domain composed of 4 alpha-helices, firmly held by a network of 4 conserved disulphide bridges. This fold presents a large internal tunnel-like cavity, which can accommodate different types of lipids. nsLTPs are involved in plant defence mechanisms against phytopathogenic bacteria and fungi, and, possibly, in the assembly of hydrophobic protective layers of surface polymers, such as cutin. In addition, several members of the nsLTP family have been identified as relevant allergens in plant foods and pollens. Their high resistance to both heat treatment and digestive proteolytic attack has been related with the induction by these allergens of severe symptoms in many patients. Therefore, they are probably primary sensitizers by the oral route. nsLTP sensitization shows an unexpected pattern throughout Europe, with a high prevalence in the Mediterranean area, but a low incidence in Northern and Central European countries. PMID- 17349820 TI - Tuberculosis of thymus--a case report. AB - Tuberculosis rarely figures in the list of thymic masses. We hereby report a case of thymic tuberculosis successfully managed with surgical excision and antituberculouschemotherapy. PMID- 17349821 TI - Papillary fibroelastoma of aortic valve: diagnosis and surgical management. AB - Papillary fibroelastoma (PFE) is a rare and benign cardiac tumour that mainly affects the valves. This tumour has the potential to cause serious life threatening thromboembolic complications. Herein, we describe successful excision of an aortic valve papillary fibroelastoma. The importance of valve sparing tumour resection is emphasised. PMID- 17349822 TI - Video-assisted thoracic surgery for pneumothorax in LAM. AB - Spontaneous pneumothorax is one of the more common presentations of lymphangioleiomyomatosis; however, recurrences are common which can be challenging to manage particularly in bilateral pneumothorax. We present a case of recurrent bilateral spontaneous pneumothorax associated with lymphangioleiomyomatosis, diagnosed intra-operatively, and confirmed by the resected lung specimen. Video-assisted thoracic surgery bullectomy and mechanical as well as talc pleurodesis was required to prevent further recurrences. The case discusses the unusual clinical course, radiological, operative and pathologic findings of the disease, and management difficulties that are distinct from other causes of spontaneous pneumothorax. PMID- 17349823 TI - Large bronchogenic cyst: diagnosis and surgical management. AB - Herein we describe a patient with an unusually large bronchogenic cyst. The removal of the cyst was performed through a mini-thoracotomy and facilitated by video-assisted thoracic surgery (VATS). PMID- 17349824 TI - The role of nurses in a chest pain unit. AB - The chest pain unit (CPU) provides a service for patients at moderate-to-low risk for acute coronary syndrome (ACS). Although the number of CPUs has continued to grow worldwide, little has been written on the specific role and contribution of nursing in CPUs. The stay of patients in the CPU can be divided into six stages: triage, diagnosis, treatment, observation/monitoring, discharge, and follow-up. CPU nurses are in a unique position to promote evidence-based practice during all of these stages. Deeper insight into the unique role of nurses in CPUs will promote understanding of what type of knowledge, skills, and attitudes are required to provide the services that will contribute to improved quality of care for chest pain patients. PMID- 17349825 TI - A vaccination strategy to enhance mucosal and systemic antibody and T cell responses against influenza. AB - Influenza infections are a major cause of mortality and morbidity worldwide. Therefore, there is a need to establish vaccines and immunization protocols that can prevent influenza infections. Herein, we show that one intranasal (IN) followed by one intramuscular (IM) immunizations with a combination of cell culture produced hemagglutinin (HA) antigens derived from 3 different influenza strains induced significantly higher serum hemagglutination inhibition (HI) and serum IgG antibody titers as well as T cell responses, compared to 2 IM, 2 IN or 1 M followed by 1 IN immunizations. Moreover, while 2 IM immunizations did not induce any antibody responses in nasal secretions or cervical lymph nodes, which drain the nasal mucosa, IN immunizations alone or in combination with IM immunization induced mucosal and local responses. These data show that the IN followed by IM immunization strategy holds promise to significantly raise serum and local antibody and T cell responses against seasonal influenza strains, and possibly pandemic influenza strains, for which no pre-existing immunity exists. PMID- 17349826 TI - New-onset seizures in adults: possible association with consumption of popular energy drinks. AB - Energy drinks contain a mixture of compounds, of which caffeine, guarana, and herbal supplements such as ginkgo and ginseng are major components. Survey of popular literature reveals anecdotal observations of adverse events associated with consumption of energy drinks. However, there are no reported cases in the published literature. We report a series of four patients who had discrete seizures on multiple occasions, following heavy consumption of energy drinks. Once the patients were abstinent from the energy drinks, no recurrent seizures were reported. We propose that the large consumption of energy drinks rich in caffeine, taurine, and guarana seed extract could have provoked these seizures. PMID- 17349827 TI - Methods for protecting silica sorbents used in high-performance liquid chromatography from strongly adsorbed impurities during purification of human recombinant insulin. AB - One of the main stages of human recombinant insulin (HRI) production is the hormone purification by means of reversed phase high-performance liquid chromatography (RP HPLC). The optimization of this stage determines the increase of the total manufacturing yield. Therefore, the cost of the sorbent used in HPLC influences the cost of the manufacturing product, i.e. HRI substance. However, resolution between HRI and its admixtures decreases with time. The reason for this is the sorbent contamination with strongly adsorbed impurities (SAI) which are accumulated during elution. In the following research several methods for sorbent protection are studied. The opinion that SAI are mainly high-molecular weight compounds was examined using gel filtration. Different sorbent types were tested for the use in guard column. The results obtained were applied and improved at preparative level. PMID- 17349828 TI - 9- and 10-Nitro-oleic acid do not interfere with the GC-MS quantitative determination of nitrite and nitrate in biological fluids when measured as their pentafluorobenzyl derivatives. AB - The nitrated lipids 9-nitro-oleic acid (9-NO(2)-OA) and 10-nitro-oleic acid (10 NO(2)-OA) have been reported to be present in blood of healthy humans. Free and esterified forms of 9-NO(2)-OA and 10-NO(2)-OA have been detected in human plasma at about 600 and 300 nM, respectively. These concentrations are of the same order of magnitude of circulating nitrite. In theory, 9-NO(2)-OA and 10-NO(2)-OA may interfere with the analysis of circulating nitrite and nitrate. In the present study, we investigated a possible interference of 9-NO(2)-OA and 10-NO(2)-OA with the GC-MS method of analysis of nitrite and nitrate involving derivatization by pentafluorobenzyl (PFB) bromide in aqueous acetone at 50 degrees C for 5 min (nitrite) or for 60 min (nitrite and nitrate). Our results show that 9-NO(2)-OA and 10-NO(2)-OA do not interfere with the GC-MS analysis of nitrite and nitrate as PFB derivatives in plasma and phosphate buffered saline when added to these matrices at supraphysiological concentrations of 1-10 microM. Thus, nitrated lipids such as 9-NO(2)-OA and 10-NO(2)-OA can be excluded as potential interfering substances in the GC-MS quantitative determination of nitrite and nitrate as their PFB derivatives. PMID- 17349829 TI - Mechanical characterization of collagen-glycosaminoglycan scaffolds. AB - Tissue engineering scaffolds are used extensively as three-dimensional analogs of the extracellular matrix (ECM). However, less attention has been paid to characterizing the scaffold microstructure and mechanical properties than to the processing and bioactivity of scaffolds. Collagen-glycosaminoglycan (CG) scaffolds have long been utilized as ECM analogs for the regeneration of skin and are currently being considered for the regeneration of nerve and conjunctiva. Recently a series of CG scaffolds with a uniform pore microstructure has been developed with a range of sizes of equiaxed pores. Experimental characterization and theoretical modeling techniques have previously been used to describe the pore microstructure, specific surface area, cell attachment and permeability of these variants. The results of tensile and compressive tests on these CG scaffolds and of bending tests on the individual struts that define the scaffold network are reported here. The CG scaffold variants exhibited stress-strain behavior characteristic of low-density, open-cell foams with distinct linear elastic, collapse plateau and densification regimes. Scaffolds with equiaxed pores were found to be mechanically isotropic. The independent effects of hydration level, pore size, crosslink density and relative density on the mechanical properties was determined. Independent control over scaffold stiffness and pore size was obtained. Good agreement was observed between experimental results of scaffold mechanical characterization and low-density, open-cell foam model predictions for uniform scaffolds. The characterized scaffold variants provide a standardized framework with defined extracellular environments (microstructure, mechanics) for in vitro studies of the mechanical interactions between cells and scaffolds as well as in vivo tissue engineering studies. PMID- 17349831 TI - The concept of acute care surgery: a vision for the not-so-distant future. PMID- 17349832 TI - At the center of the "perfect storm": the patient. PMID- 17349833 TI - Acute care surgery: the trauma surgeon's perspective. PMID- 17349834 TI - Acute care surgery: the safety net hospital model. PMID- 17349835 TI - Acute care surgery: the academic hospital's perspective. PMID- 17349836 TI - Organization of faculty practice and resident training in acute care surgery in an academic medical center. PMID- 17349837 TI - Acute care surgery: a proposed training curriculum. PMID- 17349838 TI - Acute care surgery: the surgery program director's perspective. PMID- 17349839 TI - Acute care surgery: a functioning program and fellowship training. PMID- 17349840 TI - Acute care surgery from the orthopedic surgeon's perspective: a lost opportunity. PMID- 17349841 TI - Acute care surgery: challenges and opportunities from the neurosurgical perspective. PMID- 17349842 TI - Acute care surgery: the general surgeon's perspective. PMID- 17349843 TI - Surgical hospitalism: a perspective from the community hospital. PMID- 17349844 TI - Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. AB - BACKGROUND: Tumor recurrence remains the major cause of death after curative resection for hepatocellular carcinoma (HCC). The purpose of this study was to identify risk factors for the recurrence of HCC and to examine long-term outcomes after resection. METHODS: From July 1992 to July 2004, 193 consecutive patients who underwent hepatic resection as primary therapy with curative intent for HCC were included in this single-center analysis. The perioperative mortality rate was 5%. Time to recurrence (disease-free survival) and overall survival were determined by Kaplan-Meier analysis. Demographic, tumor, and treatment characteristics were tested for their prognostic significance by univariate and multivariate analysis with the log-rank test and the Cox proportional hazards model, respectively. RESULTS: Median overall survival for the entire cohort was 71 +/- 11 months; disease-free survival was 34 months (range, 1-149 months). After a median follow-up time of 34 months, 98 patients (51%) experienced recurrent cancer; initial tumor recurrence was confined to the liver in 86 patients (88%). With the use of multivariate analysis, preoperative vascular invasion detected on radiologic imaging studies; postoperative vascular invasion found on pathologic assessment, and intermediate and poor tumor differentiation and tumor size and number were significant predictors of disease-free survival. Of the 98 patients who had tumor recurrence, 53 patients (54%) underwent additional therapy (ablation, 31 patients; re-resection, 11 patients; transarterial chemoembolization, 8 patients; liver transplantation, 3 patients) with improvement in survival. CONCLUSION: Despite recurrences in >50% of patients, long-term survival can be achieved after resection of HCC. Identification of risk factors, close follow-up evaluation, and early detection are mandatory because recurrences that are confined to the liver may be amenable to treatment with an additional survival benefit. PMID- 17349845 TI - Bile leakage after hepatectomy for hepatolithiasis: risk factors and management. AB - BACKGROUND: Bile leakage remains a major postoperative complication after liver resection. Bile leakage after hepatectomy for liver neoplasms has been well studied. However, the risk factors and management of this complication after liver resection for intrahepatic lithiasis has not been investigated. METHODS: From January 1992 to June 2004, 312 consecutive patients with intrahepatic lithiasis underwent hepatic resections Sun Yet-san University. Perioperative risk factors pertaining to the development of bile leakage were identified using univariate and multivariate analysis. The management and outcome of these patients with bile leakage were evaluated. RESULTS: Bile leakage developed in 23 (7.4%) of 312 patients. The multivariate logistic regression analysis identified that left hepatectomy (P=.024, odds ratio [OR]=3.695, 95% confidence interval [CI]: 1.185 to 11.517) and the period greater than 1 month between operative time and the latest acute cholangitis attack (P=.02, OR=4.144, 95% CI: 1.248 to 13.757) were the independent risk factors for development of bile leakage after hepatectomy for hepatolithiasis. The septic complications were higher in the patients with bile leakage than in those without bile leakage (ie, wound infection: 56.5% vs 13.5%, P=.001; subphrenic abscess: 21.7% vs 4.8%, P=.01; septicemia: 8.7% vs 0.7%, P=.029). Percutaneous drainage or combined endoscopic naso-biliary drainage was the first choice of treatment for bile leakage; 20 (87.0%) of 23 patients were treated by this method. One patient underwent re operation for diffuse peritonitis due to withdrawal of T tube inadvertently at postoperative day 1. Two patients with bile leakage were re-operated due to uncontrollable hemobilia at postoperative day 5 and 12, respectively. CONCLUSIONS: Patients who underwent hepatectomy at the period less than 1 month after the latest attack of acute cholangitis carry high risk for the development of bile leakage. Preoperative cholangiography to identify the aberrant hepatic duct for high risk patients and avoidance of hepatectomy at the acute phase of cholangitis are of critical importance to prevent bile leakage after hepatectomy. Percutaneous drainage is the primary and effective treatment for bile leakage. PMID- 17349846 TI - Clinical role of orotate phosphoribosyl transferase and dihydropyrimidine dehydrogenase in colorectal cancer treated with postoperative fluoropyrimidine. AB - BACKGROUND: Orotate phosphoribosyl transferase (OPRT) is an essential enzyme for activation of 5-fluorouracil (5-FU) and its derivatives. Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme for degradation of 5-FU. In colorectal cancer (CRC), few studies have evaluated the relationship between OPRT, DPD, and clinicopathologic features. METHODS: The study included 150 patients whose CRCs were classified into stage II to IV, and resected operatively. OPRT and DPD expression were evaluated using immunohistochemistry with new antibodies. Relationships between their expressions and clinicopathologic features. Survival curves were calculated using Kaplan-Meier method, and differences were evaluated with log-rank test. Cox proportional hazards model was also used. RESULTS: OPRT expression showed a negative correlation with advances in venous invasion (P=.041), though DPD expression showed positive correlations with advances in venous invasion (P=.0053), and cancer stage (P=.0064). The patients survival rates were higher in those OPRT(+) than in those OPRT(-) (P=.004), and higher in those DPD(-) than in those DPD(+) (P=.008). The estimated hazard ratio for patients death with OPRT and DPD expression were 2.43 and 6.55 (P=.0047 and .0096) respectively. CONCLUSIONS: OPRT expression was associated negatively with CRC progression and related with better prognosis, although DPD expression was positively correlated with CRC progression and related with poor prognosis. The overall patients survival rates were best in the patients OPRT(+)DPD(-), and worst in those OPRT(-)DPD(+) in treatment with fluoropyrimidine after operation. PMID- 17349847 TI - Objective evidence that bariatric surgery improves obesity-related obstructive sleep apnea. AB - BACKGROUND: Obstructive sleep apnea (OSA) is associated with obesity. Our aim in this study is to report objective improvement of obesity-related OSA and sleep quality after bariatric surgery. METHODS: Prospective bariatric patients were referred for polysomnography if they scored >or=6 on the Epworth Sleepiness Scale. The severity of OSA was categorized by the respiratory disturbance index (RDI) as follows: absent, 0 to 5; mild, 6 to 20; moderate, 21 to 40; and severe, <40. Patients were referred for repeat polysomnography 6 to 12 months after bariatric surgery or when weight loss exceeded 75 lbs. Means were compared using paired t tests. Chi-square tests and linear regression models were used to assess associations between clinical parameters and RDI; P<.05 was considered statistically significant. RESULTS: Of 349 patients referred for polysomnography, 289 patients had severe (33%), moderate (18%), and mild (32%) OSA; 17% had no OSA. At a median of 11 months (6 to 42 months) after bariatric surgery, mean body mass index (BMI) was 38 +/- 1 kg/m2 (P<.01 vs 56 +/- 1 kg/m2 preoperatively) and the mean RDI decreased to 15 +/- 2 (P<.01 vs 51 +/- 4 preoperatively) in 101 patients who underwent postoperative polysomnography. In addition, minimum oxygen saturation, sleep efficiency, and rapid eye movement latency improved, and the requirement for continuous positive airway pressure was reduced (P or =64 years predicted for higher withdrawal rates. Patients with a history of CHF had lower withdrawal rates. Mean QTc interval was prolonged by 2.4 ms. No treatment discontinuations occurred due to QTc prolongation, and no Torsades de Pointes was reported. Sixty-four deaths occurred during a total of 2,102 patient-years (3.0% annually) during the ROLE program. When extending observations to all patients exposed to ranolazine during the double-blind trials (n = 972) preceding the ROLE program, annual mortality was 2.8% compared with >5% as predicted by DTS. CONCLUSIONS: Long-term therapy with ranolazine seems well tolerated in high-risk CHD patients. Survival analyses suggest that symptomatic improvements attributable to ranolazine are not offset by increased mortality. PMID- 17349882 TI - Treatment with ezetimibe plus low-dose atorvastatin compared with higher-dose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets? AB - OBJECTIVES: We sought to test the platelet inhibitory and anti-inflammatory effects of a higher statin dosage compared with combined treatment with ezetimibe plus a low statin dose. BACKGROUND: Reducing the level of low-density lipoprotein cholesterol (LDL-C) with statins induces important pleiotropic effects such as platelet inhibition. An insufficient LDL-C reduction often is treated with ezetimibe, an intestinal cholesterol absorption inhibitor, in combination with a low statin dose. It is not known whether this combination therapy has the same pleiotropic effects as a statin monotherapy. METHODS: Fifty-six patients with coronary artery disease were assigned randomly to receive either 40 mg/day of atorvastatin or 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin for 4 weeks. The levels of LDL-C, platelet activation markers after stimulation, platelet aggregation, and plasma chemokine levels (i.e., regulated on activation normally T-cell expressed and secreted [RANTES]) were measured before and after changing lipid-lowering medication. RESULTS: Platelet activation markers (P selectin) after stimulation (adenosine diphosphate) were reduced by 40 mg/day of atorvastatin (-5.2 +/- 1.6 arbitrary units) but not by ezetimibe plus low-dose atorvastatin (2.1 +/- 1.8 arbitrary units; p < 0.005) despite a similar reduction of LDL-C (atorvastatin -1.01 +/- 0.18 mmol/l vs. ezetimibe plus atorvastatin 1.36 +/- 0.22 mmol/l, p = NS). Thrombin receptor-activating peptide-induced platelet aggregation as well as plasma RANTES levels were reduced by 40 mg/day of atorvastatin but not by ezetimibe plus low-dose atorvastatin. CONCLUSIONS: Platelet reactivity and a proinflammatory chemokine were reduced more by the higher atorvastatin dose than by ezetimibe plus low-dose atorvastatin. In patients with coronary artery disease, it might be important to combine ezetimibe with higher statin dosages to benefit from cholesterol-independent pleiotropic effects. PMID- 17349883 TI - Incidence, timing, and correlates of stent thrombosis with the polymeric paclitaxel drug-eluting stent: a TAXUS II, IV, V, and VI meta-analysis of 3,445 patients followed for up to 3 years. AB - OBJECTIVES: This study sought to study stent thrombosis with the paclitaxel eluting Taxus stent. BACKGROUND: The incidence and timing of stent thrombosis after drug-eluting stent placement compared with bare-metal stent implantation remain unsettled, with consequent uncertainty about risk stratification and long term recommendations for antiplatelet medications. METHODS: This study used a patient-based meta-analysis using the 4 principal TAXUS randomized trials (3,445 patients) with a follow-up duration of > or =1 year. RESULTS: Cumulative stent thrombosis occurred in 1.28% +/- 0.31% in the Taxus group and 0.76% +/- 0.23% in the bare-metal stent group at 3 years (hazard ratio 1.51 [95% confidence interval 0.73 to 3.14], p = 0.26). Hazard ratios (per 100 patients per 6 months) were similar between the Taxus stent group (0.59 [95% confidence interval 0.22 to 0.95]) and the bare-metal stent group (0.64 [95% confidence interval 0.26 to 1.02]) through 6 months during the prescribed clopidogrel period. However, from 6 months to 3 years there were more stent thromboses in the Taxus group (hazard ratio 0.19 [95% confidence interval 0.06 to 0.32] vs. 0.02 [95% confidence interval 0.00 to 0.07], p = 0.049). Of 8 patients with Taxus-related thrombosis after 6 months, 0 were taking clopidogrel and 2 were not taking aspirin consistently. No Taxus-related stent thrombosis occurred after 2 years (922 patients thus far followed up for 3 years). Independent correlates of stent thrombosis were nonuse of clopidogrel, male gender, smoking, and possibly use of multiple nonoverlapping stents. CONCLUSIONS: Approximately 0.8% of Taxus patients have stent thrombosis in the first 6 months after stent implantation, similar to bare-metal stents. However, a modest increase in risk is present with Taxus stents beyond 6 months, possibly because of inadequate antiplatelet drug therapy. PMID- 17349884 TI - Diagnostic accuracy of rubidium-82 myocardial perfusion imaging with hybrid positron emission tomography/computed tomography in the detection of coronary artery disease. AB - OBJECTIVES: Our objective was to determine the accuracy of rubidium-82 myocardial perfusion positron emission tomography-computed tomography (PET-CT) imaging for detecting obstructive coronary artery disease (CAD). BACKGROUND: Hybrid PET-CT is a new noninvasive imaging modality for evaluating patients with known or suspected CAD. METHODS: We evaluated 64 consecutive patients with suspected CAD undergoing rest-stress rubidium-82 cardiac PET-CT (CT was only used for attenuation correction) and coronary angiography within 7 days (range 1 to 180 days). Patients with known CAD, previous myocardial infarction, or revascularization were excluded. Thirty-eight patients with a low likelihood for CAD were also studied. Obstructive CAD was defined as > or =70% diameter stenosis on angiography. RESULTS: The mean age of the patients was 62 +/- 15 years, with a body mass index of 31 +/- 8 kg/m2. Chest pain and/or dyspnea were the predominant reasons for evaluation. Stress perfusion defects were detected in 41 of 44 patients with obstructive CAD (sensitivity 93%, 95% confidence interval [CI] 87 to 99). The specificity of PET-CT was 83% (48 of 58, 95% CI 71 to 91), and its overall diagnostic accuracy was 87% (95% CI 79 to 93). All patients with a low likelihood for CAD showed normal scans, for a normalcy rate of 100% (38 of 38, 95% CI 91 to 100). The sensitivity for detecting CAD in patients with single and multivessel (> or =2 vessels) disease was 92% (22 of 24, 95% CI 74 to 99) and 95% (19 of 20, 95% CI 74 to 99), respectively. CONCLUSIONS: Myocardial perfusion PET CT affords high sensitivity and overall accuracy for detecting CAD, including patients with single-vessel disease, women, and obese patients. PMID- 17349885 TI - Integrated single-photon emission computed tomography and computed tomography coronary angiography for the assessment of hemodynamically significant coronary artery lesions. AB - OBJECTIVES: The purpose of this study was to assess the physiologic significance of coronary artery lesions with an integrated single-photon emission computed tomography (SPECT) and computed tomography coronary angiography (CTCA) device. BACKGROUND: Myocardial perfusion imaging (MPI) with SPECT is of value for assessing the physiologic significance of coronary lesions. Computed tomography coronary angiography is a new technique to noninvasively detect coronary stenosis, with high sensitivity and negative predictive value (NPV) but lower specificity and positive predictive value (PPV). The experimental SPECT/CTCA hybrid imaging device (Infinia gamma camera and LightSpeed16 CT, General Electric, Milwaukee, Wisconsin) enables concurrent assessment of coronary anatomy and myocardial perfusion. METHODS: Fifty-six patients with angina pectoris underwent single-session SPECT-MPI and CTCA with the hybrid device and coronary angiography (CA) within 4 weeks. The ability of fused SPECT/CTCA images to diagnose physiologically significant lesions showing >50% stenosis and reversible perfusion defects in the same territory was determined and compared with CTCA stand-alone. RESULTS: Of a total of 224 coronary segments in 56 patients, 12 patients and 54 segments (23%) were excluded from further analysis of CTCA. Overall, 170 coronary segments were evaluated. The sensitivity, specificity, PPV, and NPV of CTCA were 96%, 63%, 31%, and 99%, respectively, as compared with 96%, 95%, 77%, and 99%, respectively, for SPECT/CTCA. CONCLUSIONS: Hybrid SPECT/CTCA imaging results in improved specificity and PPV to detect hemodynamically significant coronary lesions in patients with chest pain. Single-photon emission computed tomography/CTCA might play a potentially important role in the noninvasive diagnosis of coronary artery disease and introduce an objective decision-making tool for assessing the need for interventions in each occluded vessel. PMID- 17349886 TI - Anatomic-functional imaging by single-photon emission computed tomography/computed tomography as the cornerstone of diagnosis and treatment for coronary patients: a glimpse into the (near) future? PMID- 17349887 TI - Evidence for functional heterogeneity of circulating B-type natriuretic peptide. AB - OBJECTIVES: These studies describe molecular forms of circulating B-type natriuretic peptide (BNP) as well as their biological activity. BACKGROUND: Increased circulating levels of immunoreactive BNP correlate with the severity of heart failure and are considered a sensitive biomarker. However, little is known about the molecular forms of circulating BNP and their biological activity. METHODS: Western blot analysis was used to characterize immunoreactive BNP species in heart failure plasma. Recombinant proBNP was assessed for reactivity in commercially available BNP assays and cell activity by cyclic guanosine monophosphate production in vascular cells. RESULTS: Heart failure plasma contained both low- (LMW-BNP) and high-molecular-weight (HMW-BNP) forms. The LMW BNP migrated similarly to a 32-amino acid BNP standard, whereas HMW-BNP, when deglycosylated, was similar to deglycosylated recombinant proBNP. Recombinant proBNP and BNP were equally recognized by the Triage BNP assay (Biosite, San Diego, California). Furthermore, recombinant proBNP and BNP were both recognized by the Advia Centaur BNP test (Bayer Diagnostics, Tarrytown, New York), but only recombinant proBNP was recognized by the Elecsys NTproBNP assay (Roche Diagnostics, Indianapolis, Indiana). Recombinant proBNP exerted significantly less biological activity than BNP on human endothelial and vascular smooth muscle cells. Comparison of effective concentration (50%) values indicates that proBNP is 6- to 8-fold less potent than BNP in these human cells. CONCLUSIONS: This study demonstrates that proBNP, constituting a substantial portion of immunoreactive BNP in heart failure plasma, possesses significantly lower biological activity than the processed 32-amino acid hormone. These results implicate a discordance in heart failure between the high circulating levels of immunoreactive BNP and hormone activity, suggesting that some patients may be in a state of natriuretic peptide deficiency. PMID- 17349888 TI - Acute phosphodiesterase 5 inhibition mimics hemodynamic effects of B-type natriuretic peptide and potentiates B-type natriuretic peptide effects in failing but not normal canine heart. AB - OBJECTIVES: The aim of this work was to test whether acute phosphodiesterase 5 (PDE5) inhibition via sildenafil (SIL) mimics and/or potentiates cardiorenal effects of exogenous natriuretic peptide (NP) infusion. BACKGROUND: Heart failure (HF) is often accompanied by elevated NP secretion yet blunted responsiveness. Such NP resistance may, in part, relate to increased cyclic guanosine monophosphate (cGMP) catabolism by PDE5. METHODS: Dogs (n = 7) were studied before and after tachypacing-induced HF. Animals received 30-min infusion of B type natriuretic peptide (BNP) (2 mug/kg bolus, 0.02 mug/kg/min), and on a separate day SIL (1 mg/kg, intravenous), followed by BNP (SIL + BNP). Phosphodiesterase 5 activity was measured in lung, vasculature, and kidney. RESULTS: At baseline (non-failing), BNP lowered central venous, pulmonary capillary wedge, diastolic, mean pulmonary artery, and mean arterial pressure. Sildenafil had no effects, and SIL + BNP was similar to BNP alone. In contrast, SIL lowered these pressures similarly to BNP in dogs with HF, and SIL + BNP was additive in further reducing pulmonary pressures over BNP alone. Plasma cGMP/plasma BNP ratio was markedly reduced with HF, indicating NP resistance. Sildenafil plus BNP increased this ratio in HF, but had no effect in non-failing animals. Sildenafil had no independent diuretic/natriuretic effects nor did it enhance BNP effects under baseline or HF conditions. In HF, PDE5 activity was significantly increased in the systemic and pulmonary vasculature and in the kidney. CONCLUSIONS: The PDE5 activity in systemic and pulmonary vasculature increases in HF rendering hemodynamic responses to PDE5 inhibition identical to those from BNP infusion. Natriuretic peptide desensitization in HF relates, in part, to increased PDE5 activity, supporting a therapeutic role for PDE5 inhibition. PMID- 17349889 TI - Heart failure: a state of brain natriuretic peptide deficiency or resistance or both! PMID- 17349890 TI - Long QT syndrome and pregnancy. AB - OBJECTIVES: This study was designed to investigate the clinical course of women with long QT syndrome (LQTS) throughout their potential childbearing years. BACKGROUND: Only limited data exist regarding the risks associated with pregnancy in women with LQTS. METHODS: The risk of experiencing an adverse cardiac event, including syncope, aborted cardiac arrest, and sudden death, during and after pregnancy was analyzed for women who had their first birth from 1980 to 2003 (n = 391). Time-dependent Kaplan-Meier and Cox proportional hazard methods were used to evaluate the risk of cardiac events during different peripartum periods. RESULTS: Compared with a time period before a woman's first conception, the pregnancy time was associated with a reduced risk of cardiac events (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.10 to 0.76, p = 0.01), whereas the 9 month postpartum time had an increased risk (HR 2.7, 95% CI 1.8 to 4.3, p < 0.001). After the 9-month postpartum period, the risk was similar to the period before the first conception (HR 0.91, 95% CI 0.55 to 1.5, p = 0.70). Genotype analysis (n = 153) showed that women with the LQT2 genotype were more likely to experience a cardiac event than women with the LQT1 or LQT3 genotype. The cardiac event risk during the high-risk postpartum period was reduced among women using beta-blocker therapy (HR 0.34, 95% CI 0.14 to 0.84, p = 0.02). CONCLUSIONS: Women with LQTS have a reduced risk for cardiac events during pregnancy, but an increased risk during the 9-month postpartum period, especially among women with the LQT2 genotype. Beta-blockers were associated with a reduction in cardiac events during the high-risk postpartum time period. PMID- 17349891 TI - Dimethylarginine dimethylaminohydrolase promotes endothelial repair after vascular injury. AB - OBJECTIVES: We sought to determine if a reduction in asymmetric dimethylarginine (ADMA) enhances endothelial regeneration. BACKGROUND: Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase (NOS). Increased plasma levels of ADMA are associated with endothelial vasodilator dysfunction in patients with vascular disease or risk factors. Asymmetric dimethylarginine is eliminated largely by the action of dimethylarginine dimethylaminohydrolase (DDAH), which exists in 2 isoforms. Dimethylarginine dimethylaminohydrolase-1 transgenic (TG) mice manifest increased DDAH activity, reduced plasma and tissue ADMA levels, increased nitric oxide synthesis, and reduced systemic vascular resistance. METHODS: The left femoral arteries of DDAH1 TG mice and wild-type (WT) mice were injured by a straight spring wire, and regeneration of the endothelial cell (EC) monolayer was assessed. Endothelial sprouting was assayed with growth factor-reduced Matrigel. RESULTS: Regeneration of the EC monolayer was more complete 1 week after injury in TG mice (WT vs. TG: 40.0 +/- 6.5% vs. 61.2 +/- 6.4%, p < 0.05). The number of CD45 positive cells at the injured sites was reduced by 62% in DDAH TG mice (p < 0.05). Four weeks after injury, the neointima area and intima/media ratio were attenuated in DDAH TG mice (WT vs. TG: 0.049 +/- 0.050 mm2 vs. 0.031 +/- 0.060 mm2, 3.1 +/- 0.5 vs. 1.7 +/- 0.2, respectively, p < 0.05). Endothelial cell sprouting from vascular segments increased in TG mice (WT vs. TG: 24.3 +/- 3.9 vs. 39.0 +/- 2.2, p < 0.05). CONCLUSIONS: We find for the first time an important role for DDAH in EC regeneration and in neointima formation. Strategies to enhance DDAH expression or activity might be useful in restoring the endothelial monolayer and in treating vascular disease. PMID- 17349893 TI - Heart failure and genomics. PMID- 17349895 TI - Cardiac mast cells: implications for heart failure. PMID- 17349896 TI - Recommendations for the standardization and interpretation of the electrocardiogram: part I: the electrocardiogram and its technology a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society endorsed by the International Society for Computerized Electrocardiology. AB - This statement examines the relation of the resting ECG to its technology. Its purpose is to foster understanding of how the modern ECG is derived and displayed and to establish standards that will improve the accuracy and usefulness of the ECG in practice. Derivation of representative waveforms and measurements based on global intervals are described. Special emphasis is placed on digital signal acquisition and computer-based signal processing, which provide automated measurements that lead to computer-generated diagnostic statements. Lead placement, recording methods, and waveform presentation are reviewed. Throughout the statement, recommendations for ECG standards are placed in context of the clinical implications of evolving ECG technology. PMID- 17349897 TI - Recommendations for the standardization and interpretation of the electrocardiogram: part II: electrocardiography diagnostic statement list a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society Endorsed by the International Society for Computerized Electrocardiology. AB - This statement provides a concise list of diagnostic terms for ECG interpretation that can be shared by students, teachers, and readers of electrocardiography. This effort was motivated by the existence of multiple automated diagnostic code sets containing imprecise and overlapping terms. An intended outcome of this statement list is greater uniformity of ECG diagnosis and a resultant improvement in patient care. The lexicon includes primary diagnostic statements, secondary diagnostic statements, modifiers, and statements for the comparison of ECGs. This diagnostic lexicon should be reviewed and updated periodically. PMID- 17349898 TI - The laryngeal tube device: a simple and timely adjunct to airway management. AB - INTRODUCTION: Endotracheal intubation (ETI) is a motor skill that demands practice. Emergency medical service providers with limited intubation experience should consider using airway adjuncts other than ETI for respiratory compromise. Prehospital ETI has been recently interrogated by evidence exposing worsened patient outcomes. The laryngeal tube (LT) airway was approved by the Food and Drug Administration in 2003 for use in the United States. Using difficult airway simulated models, we sought to describe the time difference between placing the ETI and LT and the successful placement of each adjunct in varied levels of healthcare providers. METHODS: Emergency medicine resident physicians, fourth year medical students, and paramedic students were asked to use both ETI and the LT. Subjects were timed (seconds) on ETI and LT placement on 2 different simulators (AirMan and SimMan; Laerdal Co, Wappingers Falls, NY). After ETI was complete, they were given 30 seconds to review an instructional card before placement of the LT. We measured placement time and successful placement of the device for ETI vs LT. Successful placement in the manikin was defined by a combination of breath sounds, chest rise, and absence of epigastric sounds. RESULTS: Overall mean placement time in the AirMan and SimMan for ETI was 76.4 (95% confidence interval [CI], 63.3-89.5) and 45.9 (95% CI, 41.0-50.2) seconds, respectively. Mean placement time for the LT in the AirMan and SimMan was 26.9 (95% CI, 24.3-29.5) and 20.3 (95% CI, 18.1-22.5) seconds, respectively. The time difference between ETI and LT for both simulators was significant (P < .0001). Successful placement of the LT compared with ETI in the AirMan was significant (P = .001). CONCLUSIONS: A significant time difference and simplicity exists in placing the LT, making it an attractive device for expeditious airway management. Further studies will need to validate the LT effectiveness in ventilation and oxygenation; however, its uncomplicated design allows for successful use by a variety of healthcare providers. PMID- 17349899 TI - Discordance between serum creatinine and creatinine clearance for identification of ED patients with abdominal pain at risk for contrast-induced nephropathy. AB - STUDY OBJECTIVE: Despite creatinine clearance (CrCl) being a better estimate of renal function, serum creatinine (Cr) is more commonly used to screen for renal insufficiency in patients scheduled for an enhanced abdominal computed tomography (CT) in an attempt to reduce the likelihood of contrast-induced nephropathy (CIN). Our objective was to determine the incidence of renal insufficiency (a CrCl <60 mL/min) among patients who have serum Cr below 1.5 mg/dL (the most commonly accepted Cr cutoff for the administration of intravenous contrast). This study was conducted in a population of emergency department patients with acute abdominal pain being considered for CT scan. METHODS: We performed post hoc analysis of a prospective cross-sectional study that enrolled nongravid adults with acute nontraumatic abdominal pain. Patients on dialysis were excluded. The data that we collected included demographics, history, duration/description of pain, patient reported weight, laboratory data, imaging studies, and final diagnosis. Creatinine clearance values (< or >60 mL/min) were compared to Cr values of 1.0, 1.2, 1.5, and 1.8 mg/dL to determine the percentage of patients at risk for nephropathy after contrast injection at each Cr cutoff. Descriptive statistics were used with 95% confidence intervals (CIs). RESULTS: Seven hundred sixty-five patients were enrolled; 59% (451/765) had an abdominal CT scan. Of 108 patients with CrCl less than 60 mL/min, 59 patients had a Cr less than 1.8 mg/dL (55%; 95% CI, 45%-64%); 43 had a Cr less than 1.5 mg/dL, the most commonly accepted Cr cutoff for contrast administration (40%; 95% CI, 31%-50%); 21 patients had a Cr less than 1.2 mg/dL (19%; 95% CI, 12%-28%); and 10 had a Cr less than 1.0 mg/dL (9%; 95% CI, 5%-16%). CONCLUSION: The most commonly used Cr cutoff (1.5 mg/dL) for contrast administration fails to identify 40% of the patients at risk for CIN. Future studies should address whether using CrCl rather than serum Cr decreases the incidence of contrast-induced nephropathy. PMID- 17349900 TI - High-risk ED patients with nonvariceal upper gastrointestinal hemorrhage undergoing emergency or urgent endoscopy: a retrospective analysis. AB - OBJECTIVES: The optimal timing of interventional endoscopy within the initial 24 hours remains controversial. We designed a retrospective study to compare the outcomes between emergency endoscopy (EE) and urgent endoscopy (UE) for high-risk patients with nonvariceal upper gastrointestinal hemorrhage presenting to the emergency department (ED). METHODS: The medical records of 189 patients with nonvariceal upper gastrointestinal hemorrhage who underwent endoscopy within 24 hours of admission to the ED were reviewed. Patients were divided into 2 groups: EE group (<8 hours) or UE group (8-24 hours). We compared the endoscopic findings, hemostatic procedures, rate of hemostasis, rebleeding, need for transfusion, length of hospitalization, and mortality between the 2 groups. RESULTS: There were 88 patients (47%) in the EE group and 101 patients (53%) in the UE group. Ulcers with active bleeding or exposed vessel were found more frequently in the EE group than in the UE group (19% vs 8%, P = .03; 34% vs 12%, P < .001). Fifty patients had blood retention in the stomach, especially in the EE group (40% vs 15%, P < .001). Forty-four (50%) patients in the EE group and 21 (21%) patients in the UE group received endoscopic interventions. Combination modalities of endoscopic hemostasis were more commonly used in the EE group than in the UE group (40% vs 15%, P < .001). Primary hemostasis was achieved at a rate of 95% in both groups. There was no statistical difference regarding the rate of recurrent bleeding, total amount of transfusion, length of hospital stay, and mortality rate in both groups. CONCLUSIONS: Although more active lesions were detected and more therapeutic attempts were performed in the EE group, the outcome showed no difference in both groups. Emergency endoscopy performed less than 8 hours after arrival to the ED showed no definite benefit in comparison with UE performed within 8 to 24 hours. PMID- 17349901 TI - Heparin-platelet factor 4 antibodies in patients presenting to the ED with thrombosis. AB - BACKGROUND: Patients with heparin-platelet factor 4 (PF4) antibodies, particularly platelet-activating ones, are at risk for heparin-induced thrombocytopenia if administered heparin. We determined the heparin-PF4 antibody prevalence in emergency department (ED) patients presenting with chest pain or symptoms of thrombosis. METHODS: Admission samples from 324 ED patients with chest pain or symptoms of thrombosis were tested for heparin-PF4 antibodies and, if positive, platelet-activating antibodies. RESULTS: Twenty-four (7.4%; 95% confidence interval, 4.8%-10.8%) patients had heparin-PF4 antibodies. Seropositivity occurred in 18 (9.2%) of 196 patients recently (< or =6 months) hospitalized vs 6 (4.7%) of 128 not recently hospitalized (P = .19), and in 16/231 (6.9%) patients with chest pain vs 8/93 (8.6%) with other thrombosis (P = .64). Of 22 seropositive patients retested, 8 (7 recently hospitalized) had platelet-activating antibodies. CONCLUSION: Heparin-PF4 antibody prevalence is 7.4% in ED patients with chest pain or thrombosis, with approximately 1 in 3 seropositive patients having platelet-activating antibodies. Alternative, nonheparin anticoagulation would be prudent in these at-risk patients. PMID- 17349902 TI - Pulmonary embolism risk assessment screening tools: the interrater reliability of their criteria. AB - BACKGROUND: Diagnostic evaluation for suspected pulmonary embolism (PE) is challenging. Dimerized plasmin fragment D (D-dimer) assays are increasingly used but have been validated only in "low-risk" patients. The accurate interpretation and application of risk assessment criteria are critical to the appropriate use of D-dimer. We sought to determine the interrater agreement of attending and third-year resident emergency medicine physicians in the specific elements of the Canadian and the Charlotte risk stratification tools and their clinical application. METHODS: We prospectively enrolled a convenience sample of patients presenting to an urban university emergency department with suspected PE. Standardized data collection sheets were used by an attending physician and a third-year resident physician to determine the presence or absence of risk factors included in published PE prediction instruments. Each physician was blinded to the other's results and the patients' D-dimer result. Interrater agreement was measured using kappa statistics (with 95% confidence intervals). RESULTS: Two hundred seventy-one patients were screened. The kappa scores for each risk criterion were as follows: previous deep vein thrombosis, 0.90 (95% confidence interval, 0.83-0.97); malignancy, 0.87 (0.76-0.97); deep vein thrombosis symptoms, 0.54 (0.39-0.70); immobilization, 0.41 (0.26-0.57); unexplained hypoxia, 0.58 (0.42-0.74); tachycardia, 0.94 (0.89-0.98); hemoptysis, 0.76 (0.51-1.0); and PE more likely than another diagnosis, 0.50 (0.36-0.64). CONCLUSIONS: Interrater agreement was only fair for several important risk criteria. Small differences in determining pretest probability can lead to significant variability in risk assessment and how, or whether, the diagnosis of PE is evaluated. This study raises questions about the reliability and applicability of published PE screening criteria in clinical settings. PMID- 17349903 TI - Emergency physicians can easily obtain ultrasound images of anatomical landmarks relevant to lumbar puncture. AB - INTRODUCTION: Although ultrasound has been used in administering epidural anesthesia, it is unknown if emergency physicians (EPs) can obtain ultrasound images useful for lumbar puncture. OBJECTIVE: The objective of the study was to determine EPs' ability to apply a standardized ultrasound technique for visualizing landmarks surrounding the dural space. METHODS: Two EPs sought to identify relevant anatomy in emergency patients. Visualization time for 5 anatomical structures (spinous processes or laminae, ligamentum flavum, dura mater, epidural space, subarachnoid space), body mass index, and perception of landmark palpation difficulty were recorded. RESULTS: Seventy-six subjects were enrolled. Soft tissue and bony anatomical structures were identified in all subjects. Mean body mass index was 31.4 +/- 9.8 (95% confidence interval, 29.1 33.6). High-quality images were obtained in less than 1 minute in 153 (87.9%) scans and in less than 5 minutes in 174 (100%) scans. Mean acquisition time was 57.19 seconds; SD, 68.14 seconds; range, 10 to 300 seconds. CONCLUSION: In this cohort, EPs were able to rapidly obtain high-quality ultrasound images relevant to lumbar puncture. PMID- 17349904 TI - Surge capacity: a proposed conceptual framework. AB - There is a need for emergency planners to accurately plan for and accommodate a potentially significant increase in patient volume in response to a disaster. In addition, an equally large political demand exists for leaders in government and the healthcare sector to develop these capabilities in a financially feasible and evidence-based manner. However, it is important to begin with a clear understanding of this concept on a theoretical level to create this capacity. Intuitively, it is easy to understand that surge capacity describes the ability of a healthcare facility or system to expand beyond its regular operations and accommodate a greater number of patients in response to a multiple casualty producing event. The way a response to this need is implemented will, of course, vary dramatically depending on numerous issues, including the type of event that has transpired, the planning that has occurred before its occurrence, and the resources that are available. Much has been written on strategies for developing and implementing surge capacity. However, despite the frequency with which the term is used in the medical literature and by the lay press, a clear description of surge capacity as a concept is lacking. The following article will provide this foundation. A conceptual framework of surge capacity will be described, and some new nomenclature will be proposed. This is done to provide the reader with a comprehensive yet simplified view of the various elements that make up the concept of surge capacity. This framework will cover the types of events that can cause a surge of patients, the general ways in which healthcare facilities respond to these events, and the categories of people who would make up the population of affected victims. PMID- 17349905 TI - Can ED staff accurately estimate the weight of adult patients? AB - PURPOSE: The purpose of the study was to determine the accuracy of adult weight estimates by emergency department personnel. BASIC PROCEDURES: This was a prospective, nonrandomized, observational study in a university tertiary referral center. All patient care staff and all adult patients were eligible. Patients were weighed at the bedside, then staff were asked individually for estimates. Data were analyzed using SPSS general linear modeling procedures (SPSS, Chicago, IL) to obtain a generalized analysis of variance. MAIN FINDINGS: Eighty-seven staff provided 957 estimates on 241 patients. Providers were within 5% of true weight on 33% of estimates (95% confidence interval [CI], 28-38). In our a priori subgroups, a significant difference was noted only for body mass index (BMI); percentages of correct estimates were 16% (95% CI, 0-33; n = 33) for BMI < 18.5; 38% (95% CI, 33-43; n = 654) for 18.5 < or = BMI < or = 30; and 23% (95% CI, 17 30; n = 270) for BMI > 30 (P < .001). PRINCIPAL CONCLUSIONS: Emergency department personnel provided accurate weights in only 33% of estimates. Estimates became significantly less accurate in underweight and obese patients (defined by BMI). PMID- 17349906 TI - Recognizing asymptomatic elevated blood pressure in ED patients: how good (bad) are we? AB - OBJECTIVE: This study was conducted to determine if emergency medicine (EM) physicians recognize emergency department (ED) patients with asymptomatic elevated blood pressure (AEBP) by diagnosis, treatment, or referral. The study also evaluated whether differences exist in identification of AEBP based on patient age, sex, race, or insurance status. METHODS: A retrospective chart review of all adult patients presenting to a tertiary care teaching hospital ED between April 1, 2004, and June 30, 2004, was performed. Patients were included if documented blood pressure(s) were 140/90 mm Hg or higher. Exclusion criteria included age younger than 18 years or older than 89 years, history of hypertension, admission, condition clearly defined by a hypertensive state, or blood pressure lower than 140/90 mm Hg. RESULTS: A total of 9805 charts were reviewed; 1574 (16%) patients met inclusion criteria. The average age of our study patient was 38 +/- 14 years; 51% were women and 71.8% were African American. Only 112 patients with AEBP (7%) received attention for their elevated blood pressure (ie, diagnosis, treatment, medication prescription, and/or referral). There was no statistically significant difference between patients identified with AEBP and those not recognized by ED physicians by patient age, sex, race, or insurance status. CONCLUSIONS: Emergency department physicians recognize, treat, and/or refer only a small percentage of ED patients with AEBP. No difference in identification, treatment, or referral exists based on patient age, sex, race, or insurance status. PMID- 17349907 TI - The effect of hydrocortisone on the outcome of out-of-hospital cardiac arrest patients: a pilot study. AB - OBJECTIVE: Several studies have disclosed the importance of serum adrenocorticotropic hormone and cortisol levels in resuscitation. The objective of this study was to observe the effect of hydrocortisone on the outcome of out of-hospital cardiac arrest (OHCA) patients. DESIGN: Prospective, nonrandomized, open-labeled clinical trial. SETTING: Emergency department (ED) of National Taiwan University Hospital. PATIENTS AND PARTICIPANTS: Ninety-seven nontraumatic adult OHCA victims. INTERVENTIONS: Serum adrenocorticotropic hormone and total cortisol levels were examined in all patients. The hydrocortisone group (n = 36) received 100 mg intravenous hydrocortisone during resuscitation, and the nonhydrocortisone group (n = 61) received 0.9% saline as placebo. MEASUREMENTS AND RESULTS: Comparison of return of the spontaneous circulation (ROSC) rates between the 2 groups was analyzed. The hydrocortisone group had a significantly higher ROSC rate than the nonhydrocortisone group (61% vs 39%, P = .038). Hydrocortisone administration within 6 minutes after ED arrival led to an increased ROSC rate (90% vs 50%, P = .045). The hydrocortisone and nonhydrocortisone groups did not differ in the development of electrolyte disturbances, gastrointestinal tract bleeding, or infection during early postresuscitation period (gastrointestinal bleeding: 41% vs 46%, P = .89; infection: 50% vs 75%, P = .335). There was no significant difference between the hydrocortisone and nonhydrocortisone groups in terms of 1- and 7-day survival and hospital discharge rates. CONCLUSIONS: Hydrocortisone treatment during resuscitation, particularly when administrated within 6 minutes of ED arrival, may be associated with an improved ROSC rate in OHCA patients. PMID- 17349908 TI - Application of clinical criteria for ordering radiographs to detect cervical spine fractures. AB - OBJECTIVE: The aim of the study was to determine if spinal-immobilized patients met clinical criteria for x-rays and which clinical criteria were associated with cervical fractures. METHODS: This was a prospective, observational analysis of clinical findings and radiograph results for patients transported to the emergency department in spinal immobilization by emergency medical services. The presence of altered mentation, distracting injury, cervical spine tenderness, neck pain, neurologic deficit, and palpable deformity was recorded for each subject. RESULTS: Of the 2044 subjects enrolled in the study, 1367 subjects received radiographs and 50 had cervical spine fractures. Sixty percent of subjects met some clinical criteria for radiograph ordering. Cervical spine tenderness and neurologic deficit were the only clinical criteria statistically associated with fractures. All subjects with fractures met 1 or more of the clinical criteria for radiographs. CONCLUSION: Cervical spine radiographs were ordered for a significant number of patients who did not meet the clinical criteria. However, omission of any one of the criterion other than palpable deformity would have potentially resulted in a missed fracture. Strictly following the criteria would have significantly reduced the number of cervical spine radiographs taken. PMID- 17349909 TI - The use of ultrasound to identify pertinent landmarks for lumbar puncture. AB - OBJECTIVE: This study was conducted to assess the ultrasound's (US's) ability to identify pertinent landmarks for lumbar puncture (LP) in patients of various body mass indices (BMIs) and establish spatial relationships of pertinent LP landmarks across BMIs. METHODS: In this institutional review board-approved cross-sectional study, we calculated the BMIs of eligible patients and then categorized them as normal (BMI < or =24.9), overweight (BMI 24.9-30), or obese (BMI > or =30). We recorded the difficulty in palpating traditional LP landmarks. Identification and measurement of the spatial relationships of the sacrum; spinous processes of lumbar vertebrae L3, L4, and L5; ligamentum flavum; and the spinal canal by US was attempted. RESULTS: Successful identification of pertinent structures (L4-L5 spinous processes and the spinal canal) occurred in 100% of patients with normal BMI, 95% of those who were overweight, and 74% of those who were obese (P = .011). Difficulty in palpating landmarks was noted in 5% of patients with normal BMI, 33% of those who were overweight, and 68% of those who were obese (P < .0001). In subjects with difficult-to-palpate landmarks, US identified pertinent structures in 16 of 21 (76%; 95% confidence interval, 53-92). The average distance from skin to ligamentum flavum was 44 mm in those with normal BMI, 51 mm in those who were overweight, and 64 mm in those who were obese (P < .00001); measurements between spinous processes did not vary by BMI. Overall, there was a moderate correlation (0.62) between BMI and the distance from skin to ligamentum flavum. CONCLUSION: The usefulness of US in identifying structures for LP is inversely related to BMI. Even with this limitation, US is still able to identify obese patients' pertinent landmarks almost 75% of the time. In addition, US may be helpful in identifying pertinent structures for LP in those patients with difficult-to-palpate landmarks. In patients who were obese with structures not palpable by hand or identifiable by US, other modalities should be considered. PMID- 17349910 TI - Decrease in NTproBNP plasma levels indicates clinical improvement of acute decompensated heart failure. AB - Thirty-seven consecutive patients with acute decompensated heart failure (ADHF) admitted to emergency departments for acute dyspnea were investigated. Ten patients with acute exacerbation of chronic obstructive pulmonary disease and 10 patients with hypertension crisis were also included as controls. For each patient, a plasma amino-terminal pro-B-type natriuretic peptide (NTproBNP) concentration measurement was performed at admission, 4, 12, and 24 hours later, and on the day of discharge. In patients with ADHF, the observation of a progressive reduction to a complete relief of symptoms of heart failure was accompanied by a reduction of 58% of NTproBNP plasma levels on the day of discharge. Amelioration of symptoms was accompanied by improvement of physiologic parameters and New York Heart Association functional class. In the control population (chronic obstructive pulmonary disease and hypertension crisis patients), no significant variation of NTproBNP levels in comparison with those at admission was found at each time point. In conclusion, a plasma profile obtained with sequential measurements indicates that a significant decrease in NTproBNP levels is associated with the clinical improvement of patients with ADHF at the time of discharge. PMID- 17349911 TI - Incidence of occult upper gastrointestinal bleeding in patients presenting to the ED with hematochezia. AB - OBJECTIVE: The aim of the study was to determine the incidence of nasogastric (NG) aspiration revealing a clinically unsuspected upper gastrointestinal (GI) bleeding in patients presenting to the emergency department (ED) with hematochezia. A secondary aim was to identify factors associated with an upper GI source. METHODS: Data were prospectively collected from patients 18 years or older with either bright red blood per rectum or maroon stools. Patients were excluded if their history revealed hematemesis or their examination revealed melena, bleeding from an external hemorrhoid, or anal fissure. An NG tube was placed, and initial and postlavage aspirates were inspected and tested with Gastrocult (Beckman Coulter, Inc, Palo Alto, CA) for the presence of blood. Additional data included demographics, history, vital signs, and laboratory results. RESULTS: Of 114 patients, 11 (9.6%; 95% confidence interval, 4.9%-16.6%) had a positive NG aspirate. There were no statistically significant differences in age, sex, or race between the 2 groups. Factors associated with a positive aspirate were history of upper GI bleeding (P = .04), heart rate (P = .055), and hemoglobin (P = .03). CONCLUSION: Patients presenting to the ED with hematochezia require NG tube placement and aspiration to exclude an upper GI source of bleeding. History of an upper GI bleeding and anemia were associated with a positive NG aspirate. PMID- 17349912 TI - Lack of correlation in welfare check distribution and transport patterns in a rural critical care transport service. AB - INTRODUCTION: Understanding patterns of use of emergency medical services is important for planning adequate programs, budgets, and schedules. Understanding the factors associated with use of these services can help systems target high risk populations or behaviors and allocate budgetary resources appropriately. Previous data have shown an association between the use of emergency health care use and distribution of welfare check distribution in both the United States and Canada. These data have limitations. In these studies, no attempt was made to investigate whether this increase in use was for particular types of complaints (medical or traumatic) or true outside of an urban community. The purpose of this study was to investigate whether there were similar monthly associations in patterns of use of a regional transport service for either medical or traumatic complaints. METHODS: Med Flight is a regional aeromedical service operated by the University of Wisconsin. The service provides transport services to all hospitals and emergency medical services for critically ill or injured patients inside a radius of approximately 75 miles. The program transports approximately 1200 patients per year. Data for all transports for the years 1998-2004 were obtained. Daily numbers of transports were then compared for all patients and subsets of those with specifically traumatic or cardiac-related complaints. RESULTS: There were 7756 transports during the study period: 34% of the transports were trauma related; 30% were cardiac related. There was a significant association between trauma-related flights and both month of the year (P < .0001) and day of the week (P < .001), but not for total or cardiac-related flights. There was no association between day or week of the month and transports. CONCLUSION: In contrast to previous studies, these findings show no association between use of a regional transport service and time of the month. Determinants of use of emergency services may differ between urban and nonurban areas. PMID- 17349913 TI - Acute-onset dysrhythmia heralding fulminant myocarditis and refractory cardiac arrest treated with ED cardiopulmonary bypass and extracorporeal membrane oxygenation. AB - BACKGROUND: The outcome of refractory cardiac arrest is poor. The purpose of this report is to describe two cases presenting with fulminant myocarditis and refractory cardiac arrest treated with emergency department cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), with subsequent recovery. METHODS: Report of two cases. RESULTS: Two patients presented with a new onset dysrhythmia heralding fulminant myocarditis and cardiac arrest refractory to advanced life support measures. Chest compressions and positive pressure ventilation maintained oxygenation and perfusion until CPB could be initiated in the ED followed by ECMO. Spontaneous cardiac recovery followed, associated with normal neurocognitive function. CONCLUSION: While CPB and ECMO initiation in the ED is a rare event, this could provide patients with cardiac arrest presentations suggestive of myocarditis, additional time for recovery to occur. Clinical factors suggesting a good outcome are witnessed cardiac arrest in a previously healthy child with immediate initiation of effective CPR and good brain perfusion and function as evidence by substantial bodily movement during CPR. Significant dysrhythmias in a previously healthy child may herald substantial deterioration and cardiac arrest. PMID- 17349914 TI - Reperfusion strategies in the emergency treatment of ST-segment elevation myocardial infarction. AB - Prompt restoration of blood flow is the primary treatment goal in ST-segment elevation myocardial infarction to optimize clinical outcomes. The ED plays a critical role in rapid triage, diagnosis, and management of ST-elevation myocardial infarction, and in the decision about which of the 2 recommended reperfusion options, that is, pharmacologic and mechanical (catheter-based) strategies, to undertake. Guidelines recommend percutaneous coronary intervention (PCI) if the medical contact-to-balloon time can be kept under 90 minutes, and timely administration of fibrinolytics if greater than 90 minutes. Most US hospitals do not have PCI facilities, which means the decision becomes whether to treat with a fibrinolytic agent, transfer, or both, followed by PCI if needed. Whichever reperfusion approach is used, successful treatment depends on the ED having an integrated and efficient protocol that is followed with haste. Protocols should be regularly reviewed to accommodate changes in clinical practice arising from ongoing clinical trials. PMID- 17349915 TI - Sixty-four-slice computed tomographic coronary angiography: will the "triple rule out" change chest pain evaluation in the ED? AB - Sixty-four-slice computed tomographic (CT) coronary angiography is a new technique for the noninvasive visualization of the coronary arteries. It enables noninvasive detection of coronary plaque and determination of severity without instrumentation of the heart. Although not yet commonly used in the emergency department setting, it stands poised to dramatically change the way that patients with chest pain are evaluated. In addition to evaluation of the coronary arteries, CT angiography has long been used to evaluate patients for other dangerous causes of chest pain such as aortic dissection and pulmonary embolus. Although these new scanners excel at all of these diagnostic modalities, the true excitement is in the possibility of combining several different protocols into one, allowing for multiple causes of chest pain to be "ruled out" simultaneously. This article describes the current state of the art of cardiac CT, current state of research, and current areas of controversy. PMID- 17349916 TI - Steroids in cardiac arrest: not ready for prime time? PMID- 17349917 TI - Multiple-dose activated charcoal in carbamazepine poisoning. PMID- 17349918 TI - Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells. AB - Mechanical ventilation with hyperoxia is necessary to treat critically ill patients. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), which can cause acute inflammatory lung injury. One of the major effects of hyperoxia is the injury and death of pulmonary epithelium, which is accompanied by increased levels of pulmonary proinflammatory cytokines and excessive leukocyte infiltration. A thorough understanding of the signaling pathways leading to pulmonary epithelial cell injury/death may provide some insights into the pathogenesis of hyperoxia-induced acute inflammatory lung injury. This review focuses on epithelial responses to hyperoxia and some of the major factors regulating pathways to epithelial cell injury/death, and proinflammatory responses on exposure to hyperoxia. We discuss in detail some of the most interesting players, such as NF-kappaB, that can modulate both proinflammatory responses and cell injury/death of lung epithelial cells. A better appreciation for the functions of these factors will no doubt help us to delineate the pathways to hyperoxic cell death and proinflammatory responses. PMID- 17349919 TI - Cardiovascular targets for estrogens and phytoestrogens: transcriptional regulation of nitric oxide synthase and antioxidant defense genes. AB - The benefits of dietary antioxidants against cardiovascular disease have been examined in numerous clinical trials and animal models, yet there is limited evidence linking consumption of soy isoflavones with enhanced expression of antioxidant defense genes in the vasculature. Epidemiological evidence that populations consuming soy products, rich in isoflavones genistein and daidzein, have a lower incidence of cardiovascular disease has led to the suggestion that isoflavones may be beneficial for cardiovascular health. However, population based studies cannot prove causality and may be confounded by other dietary influences. We review the molecular mechanisms (nongenomic vs genomic) by which estrogens, isoflavones, and polyphenols stimulate intracellular signal transduction pathways involved in endothelial nitric oxide production and transcriptional activation of antioxidant defense genes in vascular and other cell types. We have critically evaluated the literature that estrogenic compounds modulate vascular reactivity in vitro and in vivo, and conclude that isoflavones may protect against cardiovascular disease by virtue of their ability to activate intracellular signaling pathways, leading to increased NO bioavailability and an upregulation of antioxidant gene expression via the key transcription factors NFkappaB and Nrf2. These intracellular signaling cascades may represent a fundamental mechanism by which dietary phytoestrogens maintain redox homeostasis in the vasculature in health and disease. PMID- 17349920 TI - Use and abuse of exogenous H2O2 in studies of signal transduction. AB - The goal of this review is to present a rationale for the use of exogenous H(2)O(2), which has been demonstrated to have both toxicological and physiological signaling roles. Reasons for the use of exogenous application of nontoxic concentrations of H(2)O(2) in model systems and caveats for interpretation of the data obtained will both be presented. Briefly, an argument for the cautious use of the addition of exogenous H(2)O(2) is that, because of the permeability of cell membranes to this neutral small molecule, a concentration that is produced locally and that is necessary for the physiological action can be mimicked. On the other hand, it must be recognized that the addition of an agent or its enzymatic generation in the medium may produce reactions that may not normally occur because the total dose of H(2)O(2) and the concentration of H(2)O(2) in some cellular locations will exceed what is normally achieved even under a pathophysiological state. For this reason, this review will try to provide an unbiased balanced pros- and -cons analysis of this issue. PMID- 17349921 TI - It's hard to get downstream without a raft: a commentary on "reactive oxygen species promote raft formation in T lymphocytes". PMID- 17349922 TI - Reactive oxygen species promote raft formation in T lymphocytes. AB - Lipid rafts are involved in many cell biology events, yet the molecular mechanisms on how rafts are formed are poorly understood. In this study we probed the possible requirement of reactive oxygen species (ROS) for T-cell receptor (TCR)-induced lipid raft formation. Microscopy and biochemical analyses illustrated that blockage of ROS production, by superoxide dismutase-mimic MnTBAP, significantly reduced partitioning of LAT, phospho-LAT, and PLC-gamma in lipid rafts. Another antioxidant N-acetylcysteine (NAC) displayed a similar suppressive effect on the entry of phospho-LAT into raft microdomains. The involvement of ROS in TCR-mediated raft assembly was observed in T-cell hybridomas, T leukemia cells, and normal T cells. Removal of ROS was accompanied by an attenuated activation of LAT and PKCtheta, with reduced production of IL-2. Consistently, treating T cells with the ROS-producer tert-butyl hydrogen peroxide (TBHP) greatly enhanced membrane raft formation, distribution of phospho-LAT into lipid rafts, and increased IL-2 production. Our results indicate for the first time that ROS contribute to TCR-induced membrane raft formation. PMID- 17349923 TI - Phosphatidylserine and phosphatidylcholine-containing liposomes inhibit amyloid beta and interferon-gamma-induced microglial activation. AB - There is increasing evidence that microglial activation is one of the major pathogenic factors for Alzheimer's disease (AD) and the inhibition of the inflammatory activation of the microglia thus appears to be neuroprotective and a potentially useful treatment for AD. Phospholipids such as phosphatidylserine (PS) and phosphatidylcholine (PC) have been reported to modulate the immune function of phagocytes. In addition, PS has been reported to be a nootropics that can be used as nonprescription memory or cognitive enhancers. We therefore evaluated the effects of liposomes, which comprise both PS and PC (PS/PC liposomes), on the microglial production of tumor necrosis factor-alpha (TNF alpha), nitric oxide (NO), and superoxide (*O(2)-) induced by amyloid beta (Abeta) and interferon-gamma (IFN-gamma). Pretreatment of microglia with PS/PC liposomes considerably inhibited the TNF-alpha, NO and *O(2)- production induced by Abeta/IFN-gamma. These results suggest that PS/PC liposomes have both neuroprotective and antioxidative properties through the inhibition of microglial activation, thus supporting the nootropic and antidementia effect of PS. PMID- 17349924 TI - Protein modification elicited by oxidized low-density lipoprotein (LDL) in endothelial cells: protection by (-)-epicatechin. AB - The action of oxidatively modified low-density lipoprotein (oxLDL) on vascular endothelial cells has been proposed to be a crucial process leading to endothelial dysfunction and atherogenesis. OxLDL was shown here to elicit oxidative stress in bovine aortic endothelial cells or human umbilical vein endothelial cells, as judged by an increase in 2',7'-dichlorofluorescein fluorescence and elevated levels of carbonylated, nitrated, and 2-hydroxynonenal coupled proteins. These effects were sensitive to apocynin, indicating involvement of NADPH oxidase. A 170-kDa polypeptide carbonylated upon exposure of cells to oxLDL was identified by immunoprecipitation as EGF receptor. Immunocytochemical visualization by confocal microscopy revealed the highest levels of modified proteins in the perinuclear region. Exposure of endothelial cells to oxLDL led to modulation of the expression levels of *NO synthases; the endothelial isoform (eNOS) was down-regulated via proteasomal degradation, whereas the inducible isoform (iNOS) was up-regulated in an enzymatically active state. eNOS protein was found to be both carbonylated and nitrated upon exposure of cells to oxLDL. iNOS contributed to the generation of modified proteins as judged by the effects of the selective inhibitor L-NIO. These oxLDL-elicited changes in vascular endothelial cells described were suppressed by (-) epicatechin, a dietary polyphenol, which inhibited NADPH oxidase activity in these cells. PMID- 17349925 TI - Acute ethanol pretreatment increases FAS-mediated liver injury in mice: role of oxidative stress and CYP2E1-dependent and -independent pathways. AB - This study evaluated whether acute ethanol pretreatment potentiates Fas-mediated liver injury and if oxidative stress and CYP2E1 play a role in any enhanced hepatotoxicity. There were 3-fold increases of transaminases and more extensive apoptotic necrosis of hepatocytes and focal hemorrhages of the hepatic lobule in mice treated with Jo2 Fas agonistic antibody plus ethanol compared to saline control or to mice treated with Jo2 or ethanol alone. CYP2E1 catalytic activity and protein were increased 2-fold by the acute ethanol pretreatment. There were 2 and 2.5-fold increases of caspase-8 and caspase-3 activity and 1.6-fold increases of apoptotic-positive cells in the Jo2 plus acute ethanol group compared to the Jo2 alone group. Levels of TNF-alpha, malondialdehyde, 4 hydroxynonenal, protein carbonyl formation, 3-nitrotyrosine protein adducts, and inducible nitric oxide synthase were increased in the Jo2 plus ethanol group. The enhanced hepatotoxicity of Jo2 plus ethanol and the elevated oxidative stress and TNF levels were lower in CYP2E1 knockout mice compared to wild-type mice expressing CYP2E1 but higher than saline controls. Toxicity also declined in mice treated with gadolinium chloride, an inhibitor of the inducible nitric oxide synthase or the antioxidant, N-acetyl-L-cysteine. These data indicate that acute ethanol pretreatment is capable of elevating hepatic apoptosis and liver injury induced by Jo2 Fas agonistic antibody. The enhanced hepatotoxicity involves increased oxidative and nitrosative stress, and appears to be mediated by CYP2E1 dependent and also CYP2E1-independent mechanisms. PMID- 17349926 TI - Glutathione-induced radical formation on lactoperoxidase does not correlate with the enzyme's peroxidase activity. AB - Lactoperoxidase (LPO) is believed to serve as a mediator of host defense against invading pathogens. The protein is more abundant in body fluids such as milk, saliva, and tears. Lactoperoxidase is known to mediate the oxidation of halides and (pseudo)halides in the presence of hydrogen peroxide to reactive intermediates presumably involved in pathogen killing. More recently, LPO has been shown to oxidize a wide diversity of thiol compounds to thiyl free radicals, which ultimately lead to the formation of a protein radical characterized by DMPO immunospin trapping. In the same study by our group the authors claimed that a consequence of this protein radical formation was the inactivation of LPO (Guo et al., J. Biol. Chem.279:13272-13283; 2004). Here we demonstrate that although thiyl radical formation does lead to LPO radical production, the formation of this radical is unrelated to the enzyme's activity. We suggest the source of this misleading interpretation to be the binding of GSH to ELISA plates, which interferes with ABTS and guaiacol oxidation. In addition, DMPO-GSH-nitrone adducts bind to ELISA plates, leading to ambiguities of interpretation since we have demonstrated that DMPO-GSH nitrone does not bind to LPO, and only LPO protein-DMPO-nitrone adducts can be detected by Western blot. PMID- 17349927 TI - Mechanisms underlying the chronic pioglitazone treatment-induced improvement in the impaired endothelium-dependent relaxation seen in aortas from diabetic rats. AB - The objectives of this study were to determine the effects of chronic treatment with pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the impaired endothelium-dependent relaxation seen in aortas from established streptozotocin (STZ)-induced diabetic rats, and to identify some of the molecular mechanisms involved. Starting at 8 weeks of diabetes, pioglitazone (10 mg/kg) was administered to STZ-induced diabetic rats for 4 weeks. In untreated STZ rats (vs age-matched control rats): (1) ACh-induced relaxation, cGMP accumulation, phosphorylation of the cGMP-dependent protein kinase substrate vasodilator stimulated phosphoprotein at Ser-239 [an established biochemical end-point of nitric oxide (NO)/cGMP signaling], and Cu/Zn-superoxide dismutase (SOD) expression and SOD activity were all reduced; (2) aortic superoxide generation, nitrotyrosine expression, and NAD(P)H oxidase activity were increased; (3) plasma endothelin-1 (ET-1) and aortic c-Jun (AP-1 component) protein expressions were increased. Pioglitazone treatment markedly corrected the above abnormalities. Collectively, these results suggest that pioglitazone treatment improves endothelium-dependent relaxation by reducing oxidative stress via increased SOD activity, decreased NAD(P)H oxidase activity, and a decreased ET-1 level, and that this decreased ET-1 level may be attributable to an inhibition of the AP-1 signaling pathway. PMID- 17349928 TI - Visualization of ribonucleotide reductase catalytic oxidation establishes thioredoxins as its major reductants in yeast. AB - Thioredoxins and/or glutaredoxins assist ribonucleotide reductase, and other such enzymes that require disulfide bond reduction during their catalytic cycle. In Saccharomyces cerevisiae, the presence of either pathway is essential but which of these pathways operates in ribonucleotide reductase reduction and how this function contributes to the pathways' essential nature have not been definitively established. We have identified two in vivo redox forms of the S. cerevisiae ribonucleotide reductase R1 subunit, which correspond to catalytically reduced or oxidized enzymes. Cells lacking thioredoxins, which exhibit an elongated S phase, accumulate R1 in its oxidized form and also contain significantly decreased deoxyribonucleotide levels during the S phase. Overexpressing R1 in these cells increases both the amount of the R1 reduced form and the concentrations of deoxyribonucleotides and accelerates DNA replication. These results establish thioredoxins as the major RNR reducing system in yeast and indicate that impaired RNR reduction accounts for the S phase defects of thioredoxin-deficient cells. PMID- 17349929 TI - Full survival of paraquat-exposed rats after treatment with sodium salicylate. AB - Over the past decades, there have been numerous fatalities resulting from accidental or voluntary ingestion of the widely used herbicide paraquat dichloride (methyl viologen; PQ). Considering that the main target organ for PQ toxicity is the lung and involves the production of reactive oxygen and nitrogen species, inflammation, disseminated intravascular coagulation, and activation of transcriptional regulatory mechanisms, it may be hypothesized that an antidote against PQ poisonings should counteract all these effects. For this purpose, sodium salicylate (NaSAL) may constitute an adequate therapeutic drug, due to its ability to modulate inflammatory signaling systems and to prevent oxidative stress. To test this hypothesis, NaSAL (200 mg/kg ip) was injected in rats 2 h after exposure to a toxic dose of PQ (25 mg/kg, ip). NaSAL treatment caused a significant reduction in PQ-induced oxidative stress, platelet activation, and nuclear factor (NF)-kappaB activation in lung. In addition, histopathological lesions induced by PQ in lung were strongly attenuated and the oxidant-induced increases of glutathione peroxidase and catalase expression became absent. These effects were associated with a full survival of the PQ-treated rats (extended for more than 30 days) in comparison with 100% of mortality by Day 6 in animals exposed only to PQ, suggesting that NaSAL constitutes an important and valuable therapeutic drug to be used against PQ-induced toxicity. Indeed, NaSAL constitutes the first compound with such degree of success (100% survival). PMID- 17349930 TI - Interactions between nitric oxide and peroxynitrite during prostaglandin endoperoxide H synthase-1 catalysis: a free radical mechanism of inactivation. AB - Peroxynitrite (ONOO(-)) can serve either as a peroxide substrate or as an inactivator of prostaglandin endoperoxide H synthase-1 (PGHS-1). Herein, the mechanism of PGHS-1 inactivation by ONOO(-) and the modulatory role that nitric oxide (*NO) plays in this process were studied. PGHS-1 reacted with ONOO(-) with a second-order rate constant of 1.7 x 10(7) M(-1) s(-1) at pH 7.0 and 8 degrees C. In the absence of substrates, the enzyme was dose-dependently inactivated by ONOO(-) in parallel with 3-nitrotyrosine formation. However, when PGHS-1 was incubated with ONOO(-) in the presence of substrates, the direct reaction with ONOO(-) was less relevant and ONOO(-)-derived radicals became involved in enzyme inactivation. Bicarbonate at physiologically relevant concentrations enhanced PGHS-1 inactivation and nitration by ONOO(-), further supporting a free radical mechanism. Importantly, *NO (0.4-1.5 microM min(-1)) was able to spare the peroxidase activity of PGHS-1 but it enhanced ONOO(-)-mediated inactivation of cyclooxygenase. The observed differential effects of *NO on ONOO(-)-mediated PGHS 1 inactivation emphasize a novel aspect of the complex modulatory role that *NO plays during inflammatory processes. We conclude that ONOO(-)-derived radicals inactivate both peroxidase and cyclooxygenase activities of PGHS-1 during enzyme turnover. Finally, our results reconcile the proposed alternative effects of ONOO(-) on PGHS-1 (activation versus inactivation). PMID- 17349931 TI - Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production. AB - Pharmacological mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)) opening protects against ischemic damage and mimics ischemic preconditioning. However, physiological and pathological signaling events that open this channel are still not fully understood. We found that catalase, which removes H(2)O(2), is capable of reversing the beneficial effects of ischemic preconditioning but not of mitoK(ATP) agonist diazoxide. On the other hand, 2-mercaptopropionylglycine prevented cardioprotection in both cases, suggesting that this compound may present effects other than scavenging of reactive oxygen species. Indeed, 2 mercaptopropionylglycine and a second thiol-reducing agent, dithiothreitol, impair diazoxide-mediated activation of mitoK(ATP) in isolated heart mitochondria. This demonstrates that mitoK(ATP) activity is regulated by thiol redox status. Furthermore, stimulating the generation of endogenous mitochondrial reactive oxygen species or treating samples with H(2)O(2) strongly enhances mitoK(ATP) activity, in a manner probably dependent on redox sensors located in the channel's sulfonylurea receptor. We also demonstrate that mitoK(ATP) channel activity effectively prevents mitochondrial reactive oxygen release. Collectively, our results suggest that mitoK(ATP) acts as a reactive oxygen sensor that decreases mitochondrial free radical generation in response to enhanced local levels of oxidants. As a result, these channels regulate mitochondrial redox state under physiological conditions and prevent oxidative stress under pathological conditions such as ischemia/reperfusion. PMID- 17349932 TI - Hydrogen peroxide induces nitric oxide and proteosome activity in endothelial cells: a bell-shaped signaling response. AB - We investigated nitric oxide (*NO)-mediated proteosomal activation in bovine aortic endothelial cells (BAEC) treated with varying fluxes of hydrogen peroxide (H(2)O(2)) generated from glucose/glucose oxidase (Glu/GO). Results revealed a bell-shaped *NO signaling response in BAEC treated with Glu/GO (2-20 mU/ml). GO treatment (2 mU/ml) enhanced endothelial nitric oxide synthase (eNOS) phosphorylation and *NO release in BAEC. With increasing GO concentrations, phospho eNOS and *NO levels decreased. Bell-shaped responses in proteasomal function and *NO induction were observed in BAEC treated with varying levels of GO (2-10 mU/ml). Proteosomal activation induced in GO-treated BAEC was inhibited by N(omega)-nitro-L-arginine-methyl ester pretreatment, suggesting that *NO mediates proteasomal activation. Intracellular *NO induced by H(2)O(2) was detected by isolating the 4,5-diaminoflourescein (DAF-2)/*NO/O(2)-derived "green fluorescent product" using the high-performance liquid chromatography fluorescence technique, a more rigorous and quantitative methodology for detecting the DAF-2/*NO/O(2) reaction product. Finally, the relationships between H(2)O(2) flux, proteasomal activation/inactivation, endothelial cell survival, and apoptosis are discussed. PMID- 17349933 TI - Bcl-2 protects against hyperoxia-induced apoptosis through inhibition of the mitochondria-dependent pathway. AB - Bcl-2 is an antiapoptotic molecule that prevents oxidative stress damage and cell death. We investigated the possible protective mechanisms mediated by Bcl-2 during hyperoxia-induced cell death in L929 cells. In these cells, hyperoxia promoted apoptosis without DNA fragmentation. Overexpression of Bcl-2 significantly protected cells from oxygen-induced apoptosis, as shown by measurement of lactate dehydrogenase release, quantification of apoptotic nuclei, and detection of Annexin-V-positive cells. Bcl-2 partially prevented mitochondrial damage and interfered with the mitochondrial proapoptotic signaling pathway: it reduced Bax translocation to mitochondria, decreased the release of cytochrome c, and inhibited caspase 3 activation. However, treatment with the caspase inhibitor Z-VAD.fmk failed to rescue the cells from death, indicating that protection provided by Bcl-2 was due not only to caspase inhibition. Bcl-2 also prevented the release of mitochondrial apoptotic inducing factor, a mediator of caspase-independent apoptosis, correlating with the absence of oligonucleosomal DNA fragmentation. In addition, Bcl-2-overexpressing cells showed significantly higher intracellular amounts of glutathione after 72 h of oxygen exposure. In conclusion, our results demonstrate that the overexpression of Bcl-2 is able to prevent hyperoxia-induced cell death, by affecting mitochondria-dependent apoptotic pathways and increasing intracellular antioxidant compounds. PMID- 17349934 TI - Mitochondrial aconitase reaction with nitric oxide, S-nitrosoglutathione, and peroxynitrite: mechanisms and relative contributions to aconitase inactivation. AB - Using highly purified recombinant mitochondrial aconitase, we determined the kinetics and mechanisms of inactivation mediated by nitric oxide (*NO), nitrosoglutathione (GSNO), and peroxynitrite (ONOO(-)). High *NO concentrations are required to inhibit resting aconitase. Brief *NO exposures led to a reversible inhibition competitive with isocitrate (K(I)=35 microM). Subsequently, an irreversible inactivation (0.65 M(-1) s(-1)) was observed. Irreversible inactivation was mediated by GSNO also, both in the absence and in the presence of substrates (0.23 M(-1) s(-1)). Peroxynitrite reacted with the [4Fe-4S] cluster, yielding the inactive [3Fe-4S] enzyme (1.1 x 10(5) M(-1) s(-1)). Carbon dioxide enhanced ONOO(-)-dependent inactivation via reaction of CO(3)*(-) with the [4Fe-4S] cluster (3 x 10(8) M(-1) s(-1)). Peroxynitrite also induced m aconitase tyrosine nitration but this reaction did not contribute to enzyme inactivation. Computational modeling of aconitase inactivation by O(2)*(-) and *NO revealed that, when NO is produced and readily consumed, measuring the amount of active aconitase remains a sensitive method to detect variations in O(2)*(-) production in cells but, when cells are exposed to high concentrations of NO, aconitase inactivation does not exclusively reflect changes in rates of O(2)*(-) production. In the latter case, extents of aconitase inactivation reflect the formation of secondary reactive species, specifically ONOO(-) and CO(3)*(-), which also mediate m-aconitase tyrosine nitration, a footprint of reactive *NO derived species. PMID- 17349935 TI - Dietary cysteine alleviates sucrose-induced oxidative stress and insulin resistance. AB - Diets that promote oxidative stress favor impairment in glucose homeostasis. In this context, increasing the cysteine intake may be beneficial by maintaining glutathione status. We have investigated the effects of dietary cysteine on oxidative stress and glucose homeostasis in rats fed a high-sucrose (HS) diet. Rats were assigned for 6 weeks to a standard diet or to HS diets in which the protein source was either an alpha-lactalbumin-rich whey concentrate (a cysteine rich protein) or the total milk proteins alone or supplemented with 5.8 or 20 g N acetylcysteine per kilogram of food. Increasing the cysteine intake prevented HS induced oxidative stress, as assessed by blood and tissue glutathione and carbonyl levels. At the same time, the HS-induced glucose intolerance, impaired postprandial glycemic control, and decrease in muscle and liver insulin-induced activation of insulin receptor substrate 1 and Akt were prevented by increasing the level of dietary cysteine, a major original finding. Of great interest was the observation that all beneficial effects of cysteine supplementation were duplicated by the consumption of a cysteine-rich protein. These data show that increasing the cysteine intake limits HS-induced impairment of glucose homeostasis and suggest that these effects are mediated by a reduction in oxidative stress. PMID- 17349936 TI - Glucose-induced cataract in CuZn-SOD null lenses: an effect of nitric oxide? AB - Lenses from mice lacking the antioxidant enzyme copper-zinc superoxide dismutase (SOD1) show elevated levels of superoxide radicals and are prone to developing cataract when exposed to high levels of glucose in vitro. As superoxide may react further with nitric oxide, generating cytotoxic reactive nitrogen species, we attempted to evaluate the involvement of nitric oxide in glucose-induced cataract. Lenses from SOD1-null and wild-type mice were incubated with high or normal levels of glucose (55.6 and 5.56 mM). A nitric oxide synthase inhibitor (L NAME) or a nitric oxide donor (DETA/NO) was added to the culture medium. Cataract development was assessed using digital image analysis of lens photographs and cell damage by analyzing the leakage of lactate dehydrogenase. The levels of superoxide radicals in the lenses were also measured. L-NAME was found to reduce cataract development and cell damage in the SOD1-null lenses exposed to high glucose. On the other hand, DETA/NO accelerated cataract development, especially in the SOD1-null lenses. These lenses also showed a higher leakage of lactate dehydrogenase than wild-type controls. We conclude that a combination of high glucose and absence of SOD1 increases the formation of cataract and that nitric oxide probably contributes to this process. PMID- 17349937 TI - Membrane cholesterol in the regulation of aminophospholipid asymmetry and phagocytosis in oxidized erythrocytes. AB - Cholesterol is known to affect several membrane functions, including membrane susceptibility to oxidative stress. In order to gain a better understanding of the relationship between cholesterol contents, structural integrity, and degree of survival in oxidatively stressed erythrocytes, here we analyzed the transbilayer phospholipid distribution, the morphology, and the degree of clearance observed in cholesterol-modified (enriched or depleted) and unmodified (control) erythrocytes exposed to tert-butylhydroperoxide. We report that the modification of cholesterol contents in erythrocytes promotes the externalization of phosphatidylserine (PS) to the membrane surface, which is consistent with a concomitant inhibition of aminophospholipid translocase (APLT) and an increased uptake of modified erythrocytes by macrophages. Moreover, cholesterol depletion modifies the transbilayer aminophospholipid distribution induced by oxidative stress to a great extent, significantly increasing PS externalization, which is associated with the strongest decrease in APLT activity. The loss of normal PS asymmetry is positively correlated with enhanced phagocytosis, and an increase in echinocyte forms is observed in all oxidized erythrocytes. We envisage that PS externalization could be due, at least in part, to the decrease in APLT activity induced by oxidative stress, the activity of which is also dependent on membrane cholesterol contents. PMID- 17349938 TI - Compartment-dependent management of H(2)O(2) by peroxisomes. AB - Peroxisomes (PO) are essential and ubiquitous single-membrane-bound organelles whose ultrastructure is characterized by a matrix and often a crystalloid core. A unique feature is their capacity to generate and degrade H(2)O(2) via several oxidases and catalase, respectively. Handling of H(2)O(2) within PO is poorly understood and, in contrast to mitochondria, they are not regarded as a default H(2)O(2) source. Using an ultrasensitive luminometric H(2)O(2) assay, we show in real time that H(2)O(2) handling by matrix-localized catalase depends on the localization of H(2)O(2) generation in- and outside the PO. Thus, intact PO are inefficient at degrading external but also internal H(2)O(2) that is generated by the core-localized urate oxidase (UOX). Our findings suggest that, in addition to the PO membrane, the matrix forms a significant diffusion barrier for H(2)O(2). In contrast, matrix-generated H(2)O(2) is efficiently degraded. We further show that the tubular structures in crystalloid cores of UOX are associated with and perpendicularly oriented toward the PO membrane. Studies on metabolically active liver slices demonstrate that UOX directly releases H(2)O(2) into the cytoplasm, with the 5-nm primary tubules in crystalloid cores serving as exhaust conduits. Apparently, PO are inefficient detoxifiers of external H(2)O(2) but rather can become an obligatory source of H(2)O(2)--an important signaling molecule and a potential toxin. PMID- 17349939 TI - Statistical deformable bone models for robust 3D surface extrapolation from sparse data. AB - A majority of pre-operative planning and navigational guidance during computer assisted orthopaedic surgery routinely uses three-dimensional models of patient anatomy. These models enhance the surgeon's capability to decrease the invasiveness of surgical procedures and increase their accuracy and safety. A common approach for this is to use computed tomography (CT) or magnetic resonance imaging (MRI). These have the disadvantages that they are expensive and/or induce radiation to the patient. In this paper we propose a novel method to construct a patient-specific three-dimensional model that provides an appropriate intra operative visualization without the need for a pre or intra-operative imaging. The 3D model is reconstructed by fitting a statistical deformable model to minimal sparse 3D data consisting of digitized landmarks and surface points that are obtained intra-operatively. The statistical model is constructed using Principal Component Analysis from training objects. Our deformation scheme efficiently and accurately computes a Mahalanobis distance weighted least square fit of the deformable model to the 3D data. Relaxing the Mahalanobis distance term as additional points are incorporated enables our method to handle small and large sets of digitized points efficiently. Formalizing the problem as a linear equation system helps us to provide real-time updates to the surgeons. Incorporation of M-estimator based weighting of the digitized points enables us to effectively reject outliers and compute stable models. We present here our evaluation results using leave-one-out experiments and extended validation of our method on nine dry cadaver bones. PMID- 17349940 TI - Disaster: nursing homes need to be prepared. PMID- 17349942 TI - To evacuate or not to evacuate: lessons learned from Louisiana nursing home administrators following Hurricanes Katrina and Rita. AB - OBJECTIVES: To evaluate the "lessons learned" by Louisiana Nursing Home (NH) administrative directors (ADs) forced to make decisions relating to resident evacuation before Hurricanes Katrina and Rita and determine how emergency planning has changed in those NHs. DESIGN: Twenty in-depth telephone interviews followed by a focus group conducted in New Orleans. SETTING: Louisiana NHs in parishes affected by Hurricanes Katrina and Rita. PARTICIPANTS: Twenty ADs employed by affected NHs during August and September 2005. MEASUREMENTS: Qualitative data sources consisted of transcribed telephone and focus group interviews. Data were analyzed using narrative summary analysis and descriptive data were tabulated using an abstraction tool. RESULTS: Nine of 20 NHs evacuated before the hurricanes and 11 sheltered in place. Six additional NHs evacuated following the storms. The most common perceived consequences related to the evacuation process were resident morbidity or mortality (6 of 15), transportation issues (5 of 15), and staffing deficiencies (3 of 15). Common findings among the NHs that sheltered in place included supply shortages (8 of 11), facility damage (5 of 11), and staffing issues (4 of 11). CONCLUSION: Respondents noted 4 general themes during the interviews and focus group session: (1) ADs felt abandoned by the state and federal emergency response apparatus during and after the hurricanes, and continue to feel that they are not a priority; (2) there is substantial physical and technical difficulty in evacuating frail NH residents; (3) staff retention remains a critical problem regardless of the evacuation decision; (4) there are key "lessons learned" that can be incorporated into future disaster planning. PMID- 17349943 TI - The utility of PET brain imaging in the initial evaluation of dementia. AB - Given the challenges and benefits of timely and accurate diagnosis of neurodegenerative disorders and the importance of appropriate subsequent treatments, physicians and patients alike desire tools that aid in diagnosing dementia as early and as precisely as possible. One of these tools may be functional brain imaging, specifically positron emission tomography (PET). Recent technological advancements, ongoing research studies, and approval for reimbursement by various insurance companies and Medicare, under certain circumstances, have led to an increased interest in the use of this tool in the evaluation of dementia. This article will review PET brain imaging in the initial assessment and diagnosis of dementia, including its place in current guidelines and role in diagnostic algorithms, its applicability in differentiating among various dementia syndromes and major psychiatric disorders, and some of the controversies surrounding its utility in general clinical practice. PMID- 17349944 TI - Substantial daily pain among nursing home residents. AB - OBJECTIVE: To evaluate the prevalence of substantial daily pain among nursing home residents aged 65 and older. DESIGN, SETTING, AND METHODS: The Minimum Data Set (MDS) annual or admission assessment, available September 2002, for Alabama nursing home residents was used. Logistic regression was used to examine the association of such pain with nursing home characteristics as well as resident specific factors. RESULTS: The analysis is based on 27,628 nursing home residents 65 and older with mean age of 82.8 years; 20% African American; 25% male. Seventeen percent had substantial daily pain. By nursing home, reported substantial daily pain prevalence ranged from 0% to 54.7%. The prevalence of pain was less in smaller nursing homes (P < .001). Bivariate correlations were significant for all sociodemographic and mental status variables; number of medications; dementia; thyroid, musculoskeletal, neurological, pulmonary, and sensory disorders; allergies; anemia; and cancer. Factors independently correlated with substantial daily pain included (odds ratio, 95% confidence interval) sociodemographic characteristics: white race (1.5, 1.3-1.7), female (1.3, 1.2-1.5), married (1.1, 1.0-1.2), admission within year (2.0, 1.8-2.1); nursing home characteristics: nonprofit or government financing (1.3, 1.2-1.5), greater number of residents (1.4, 1.3-1.5); subject-specific conditions: no cognitive impairment (1.6, 1.5-1.7), communication ability (1.4, 1.2-1.5), sad mood/depression (1.5, 1.4-1.6), taking 10 or more medications (2.0, 1.9-2.2), musculoskeletal disease (1.9, 1.7-2.0), anemia (1.1, 1.0-1.2), and cancer (1.6, 1.4-1.8). Lower odds of substantial daily pain were associated with older age, rural locale, dementia, and thyroid, neurological, pulmonary, and sensory disorders. DISCUSSION: This study highlights within-state variation in MDS reporting by nursing home as well as resident-specific factors associated with daily substantial pain. Rural, for-profit, and low-occupancy nursing homes had less documented pain. Communication ability and not having cognitive impairment were important factors in having such pain reported. PMID- 17349945 TI - Family member perception of quality of their visits with relatives with dementia: a pilot study. AB - OBJECTIVE: The purpose of the investigation was to identify factors influencing quality of visits with institutionalized patients suffering from dementia. STUDY DESIGN: Two focus groups of family members of patients residing on a Dementia Special Care Unit. SETTING: Dementia Special Care Unit in a Veterans Administration Hospital. PARTICIPANTS: Spouses and adult children of institutionalized patients with dementia. INTERVENTION: During the focus group the family members were asked to identify factors that contribute to the quality of their visits with loved ones suffering from dementia. The group sessions were recorded and transcribed verbatim. Data obtained during the sessions were analyzed and specific factors affecting the visiting experience were identified. RESULTS: Numerous factors affecting the visiting experience were identified and were grouped into personal, interpersonal, and environmental domains. CONCLUSIONS: The presence of visitors in the long-term care setting is very important. Visiting provides a link with the families and communities, and promotes the quality of life for patients with dementia. Satisfying experience during the visits helps the families to enjoy the interaction and promotes their involvement with their institutionalized relatives. Health care providers should make efforts to improve the quality of visits. PMID- 17349946 TI - Nursing home medication administration cost minimization analysis. AB - OBJECTIVES: To assess the time it takes nurses to administer medications in the nursing home setting, to calculate nursing cost of medication administration, and to determine whether using extended-release products are justified by decreasing nursing costs. DESIGN: Cost-minimization analysis using observational data from a time-motion analysis. SETTING: Two 150-bed nursing homes in rural eastern North Carolina. PARTICIPANTS: Nurses working during first and second shifts. MEASUREMENTS: Nurses were timed as they each administered medications to 12 patients. The mean time required to administer each dosage form was calculated. The cost of nursing time was based on the average nursing staff salary of $20.45 per hour as reported by the directors of nursing. Time and cost to dispense one more medication during an existing medication pass and an additional medication pass are calculated. RESULTS: The time to administer an additional dose of an oral medication to one patient was 45.01 seconds during an already scheduled medication pass and 63.05 seconds during a new medication pass. The cost of adding an oral medication once a day for a patient will cost $7.67 per month if administered at the same time as other medications or $10.74 per month if a new medication pass is required. The administration of other dosage forms, such as crushed, percutaneous enteroscopic gastrostomy, injection, and patch was more time involved and, thus, costlier. Formulas are provided to calculate medication administration cost based on local salary. CONCLUSIONS: Nursing time and costs for medication administration in the nursing home are great and should be considered when selecting a product. This may justify the selection of higher cost extended-release products. PMID- 17349947 TI - Development and implementation of the TrAC (Tracking After-hours Calls) database: a tool to collect longitudinal data on after-hours telephone calls in long-term care. AB - INTRODUCTION: Effective telephone communication between long-term care (LTC) nurses and physicians is an integral part of high-quality care, yet little is known about this key aspect of LTC practice. The authors describe the development and implementation of the TrAC (Tracking After-hours Calls) system, an electronic database designed to collect longitudinal data on after-hours telephone calls from LTC facilities. DEVELOPMENT: A relational database was developed to systematically record key characteristics of calls received from LTC facilities, including the date, time, location and reason for each call (new symptom/event, lab or x-ray report, verify admission orders, order clarification, other). Physicians also recorded their actions based on the call and their impression of 5 aspects of the telephone encounter. A daily report of after-hours calls was generated using the electronic call log software and delivered to patients' primary care providers and LTC facility personnel. IMPLEMENTATION: Eight geriatric medicine fellows and 40 internal medicine interns participated in the initial implementation of the database. Over a 10-month period, data were collected on 2015 calls. Call reporting was sustained over time (mean calls per week 47.6, SD 8.2) and data collection was complete (<1.5% missing values). The most common reasons for calls to the physician were falls (17%) and lab or x-ray reports (11%). Overall, 75% of calls were for clinical problems. At the end of the study period, the geriatrics clinical group decided to adapt the TrAC database for continued use in routine clinical practice. CONCLUSION: Use of the TrAC database was a feasible way to collect longitudinal data on telephone communication between nurses and physicians in LTC. The system can be used for the development and evaluation of quality improvement programs and as an educational tool in geriatrics training programs. PMID- 17349948 TI - The application of evidence-based principles of care in older persons (issue 5): Alzheimer's disease. PMID- 17349949 TI - The medical director's role: neglect in long-term care. PMID- 17349950 TI - Barriers to effective palliative care in the nursing home setting. PMID- 17349952 TI - P bodies and the control of mRNA translation and degradation. AB - Recent results indicate that many untranslating mRNAs in somatic eukaryotic cells assemble into related mRNPs that accumulate in specific cytoplasmic foci referred to as P bodies. Transcripts associated with P body components can either be degraded or return to translation. Moreover, P bodies are also biochemically and functionally related to some maternal and neuronal mRNA granules. This suggests an emerging model of cytoplasmic mRNA function in which the rates of translation and degradation of mRNAs are influenced by a dynamic equilibrium between polysomes and the mRNPs seen in P bodies. Moreover, some mRNA-specific regulatory factors, including miRNAs and RISC, appear to repress translation and promote decay by recruiting P body components to individual mRNAs. PMID- 17349954 TI - A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination. AB - The ubiquitin (Ub)-conjugating enzyme Ubc13 is implicated in Rad6/Rad18-dependent postreplication repair (PRR) in budding yeast, but its function in vertebrates is not known. We show here that disruption or siRNA depletion of UBC13 in chicken DT40 or human cells confers severe growth defects due to chromosome instability, and hypersensitivity to both UV and ionizing radiation, consistent with a conserved role for Ubc13 in PRR. Remarkably, Ubc13-deficient cells are also compromised for DNA double-strand break (DSB) repair by homologous recombination (HR). Recruitment and activation of the E3 Ub ligase function of BRCA1 and the subsequent formation of the Rad51 nucleoprotein filament at DSBs are abolished in Ubc13-deficient cells. Furthermore, generation of ssDNA/RPA complexes at DSBs is severely attenuated in the absence of Ubc13. These data reveal a critical and unexpected role for vertebrate Ubc13 in the initiation of HR at the level of DSB processing. PMID- 17349953 TI - Rad50 adenylate kinase activity regulates DNA tethering by Mre11/Rad50 complexes. AB - Mre11 and Rad50 are the catalytic components of a highly conserved DNA repair complex that functions in many aspects of DNA metabolism involving double-strand breaks. The ATPase domains in Rad50 are related to the ABC transporter family of ATPases, previously shown to share structural similarities with adenylate kinases. Here we demonstrate that Mre11/Rad50 complexes from three organisms catalyze the reversible adenylate kinase reaction in vitro. Mutation of the conserved signature motif reduces the adenylate kinase activity of Rad50 but does not reduce ATP hydrolysis. This mutant resembles a rad50 null strain with respect to meiosis and telomere maintenance in S. cerevisiae, correlating adenylate kinase activity with in vivo functions. An adenylate kinase inhibitor blocks Mre11/Rad50-dependent DNA tethering in vitro and in cell-free extracts, indicating that adenylate kinase activity by Mre11/Rad50 promotes DNA-DNA associations. We propose a model for Rad50 that incorporates both ATPase and adenylate kinase reactions as critical activities that regulate Rad50 functions. PMID- 17349955 TI - Structure of a herpesvirus-encoded cysteine protease reveals a unique class of deubiquitinating enzymes. AB - All members of the herpesviridae contain within their large tegument protein a cysteine protease module that displays deubiquitinating activity. We report the crystal structure of the cysteine protease domain of murine cytomegalovirus M48 (M48(USP)) in a complex with a ubiquitin (Ub)-based suicide substrate. M48(USP) adopts a papain-like fold, with the active-site cysteine forming a thioether linkage to the suicide substrate. The Ub core participates in an extensive hydrophobic interaction with an exposed beta hairpin loop of M48(USP). This Ub binding mode contributes to Ub specificity and is distinct from that observed in other deubiquitinating enzymes. Both the arrangement of active-site residues and the architecture of the interface with Ub lead us to classify this domain as the founding member of a previously unknown class of deubiquitinating enzymes. PMID- 17349956 TI - Evolution of Ime2 phosphorylation sites on Cdk1 substrates provides a mechanism to limit the effects of the phosphatase Cdc14 in meiosis. AB - Progression through meiosis in yeast is governed by the cyclin-dependent kinase Cdk1, in concert with a related kinase called Ime2. It remains unclear how these kinases collaborate to meet the unique demands of meiotic progression. We demonstrate that Ime2 and Cdk1 phosphorylate an overlapping substrate set and that the two kinases overlap functionally as inhibitors of the ubiquitin ligase APC(Cdh1) and replication origin licensing. Surprisingly, Ime2 phosphorylates Cdk1 substrates at distinct phosphorylation sites that are highly resistant to dephosphorylation by the phosphatase Cdc14. We propose that Ime2-dependent phosphorylation of a subset of cell-cycle proteins limits the effects of Cdc14 in meiosis. PMID- 17349957 TI - Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. AB - Interleukin (IL)-1beta maturation is accomplished by caspase-1-mediated proteolysis, an essential element of innate immunity. NLRs constitute a recently recognized family of caspase-1-activating proteins, which contain a nucleotide binding oligomerization domain and leucine-rich repeat (LRR) domains and which assemble into multiprotein complexes to create caspase-1-activating platforms called "inflammasomes." Using purified recombinant proteins, we have reconstituted the NALP1 inflammasome and have characterized the requirements for inflammasome assembly and caspase-1 activation. Oligomerization of NALP1 and activation of caspase-1 occur via a two-step mechanism, requiring microbial product, muramyl-dipeptide, a component of peptidoglycan, followed by ribonucleoside triphosphates. Caspase-1 activation by NALP1 does not require but is enhanced by adaptor protein ASC. The findings provide the biochemical basis for understanding how inflammasome assembly and function are regulated, and shed light on NALP1 as a direct sensor of bacterial components in host defense against pathogens. PMID- 17349958 TI - DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage. AB - Genotoxic stress exerts biological activity by activating downstream effectors, including the p53 tumor suppressor. p53 regulates cell-cycle checkpoint and induction of apoptosis in response to DNA damage; however, molecular mechanisms responsible for committing to these distinct functions remain to be elucidated. Recent studies demonstrated that phosphorylation of p53 at Ser46 is associated with induction of p53AIP1 expression, resulting in commitment to apoptotic cell death. In this regard, the role for Ser46 kinases in p53-dependent apoptosis has been established; however, the kinases responsible for Ser46 phosphorylation have yet to be identified. Here, we demonstrate that the dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) directly phosphorylates p53 at Ser46. Upon exposure to genotoxic stress, DYRK2 translocates into the nucleus for Ser46 phosphorylation. Consistent with these results, DYRK2 induces p53AIP1 expression and apoptosis in a Ser46 phosphorylation-dependent manner. These findings indicate that DYRK2 regulates p53 to induce apoptosis in response to DNA damage. PMID- 17349959 TI - MDM2-regulated degradation of HIPK2 prevents p53Ser46 phosphorylation and DNA damage-induced apoptosis. AB - In response to DNA damage, p53 induces either cell-cycle arrest or apoptosis by differential transcription of several target genes and through transcription independent apoptotic functions. p53 phosphorylation at Ser46 by HIPK2 is one determinant of the outcome because it takes place only upon severe, nonrepairable DNA damage that irreversibly drives cells to apoptosis. Here, we show that p53 represses its proapoptotic activator HIPK2 via MDM2-mediated degradation, whereas a degradation-resistant HIPK2 mutant has increased apoptotic activity. Upon cytostatic, nonsevere DNA damage, inhibition of HIPK2 degradation is sufficient to induce p53Ser46 phosphorylation and apoptosis, converting growth-arresting stimuli to apoptotic ones. These findings establish HIPK2 as an MDM2 target and support a model in which, upon nonsevere DNA damage, p53 represses its own phosphorylation at Ser46 due to HIPK2 degradation, supporting the notion that the cell-cycle-arresting functions of p53 include active inhibition of the apoptotic ones. PMID- 17349960 TI - Structural basis for interaction of the ribosome with the switch regions of GTP bound elongation factors. AB - Elongation factor G (EF-G) catalyzes tRNA translocation on the ribosome. Here a cryo-EM reconstruction of the 70S*EF-G ribosomal complex at 7.3 A resolution and the crystal structure of EF-G-2*GTP, an EF-G homolog, at 2.2 A resolution are presented. EF-G-2*GTP is structurally distinct from previous EF-G structures, and in the context of the cryo-EM structure, the conformational changes are associated with ribosome binding and activation of the GTP binding pocket. The P loop and switch II approach A2660-A2662 in helix 95 of the 23S rRNA, indicating an important role for these conserved bases. Furthermore, the ordering of the functionally important switch I and II regions, which interact with the bound GTP, is dependent on interactions with the ribosome in the ratcheted conformation. Therefore, a network of interaction with the ribosome establishes the active GTP conformation of EF-G and thus facilitates GTP hydrolysis and tRNA translocation. PMID- 17349961 TI - An essential function of the SRC-3 coactivator in suppression of cytokine mRNA translation and inflammatory response. AB - Steroid receptor coactivator-3 (SRC-3) is a transcriptional coactivator for nuclear receptors and other transcription factors. Although multiple physiological roles of SRC-3 have been revealed, its involvement in the inflammatory process remains unclear. Herein we show that SRC-3(-/-) mice are markedly hypersensitive to LPS-induced endotoxic shock. In response to LPS, SRC 3(-/-) macrophages produce significantly more proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1beta than wild-type controls, although they express similar amounts of cytokine mRNAs, suggesting that SRC-3 can exert effects at translational levels. Increased heavy polysome-associated TNF-alpha and IL-1beta mRNAs in SRC-3(-/-) macrophages implicate SRC-3 as a translational repressor. SRC 3 may cooperate with other translational repressors such as TIA-1 and TIAR to regulate cytokine mRNA translation. Collectively, our studies reveal an essential function of SRC-3 as a coordinator of inflammatory mRNA translation and as a physiologic protective factor against the lethal endotoxic shock triggered by an acute inflammatory response. PMID- 17349962 TI - c-Src activates endonuclease-mediated mRNA decay. AB - The mRNA endonuclease PMR1 initiates mRNA decay by forming a selective complex with its translating substrate mRNA. Previous work showed that the ability of PMR1 to target to polysomes and activate decay depends on the phosphorylation of a tyrosine residue at position 650. The current study shows that c-Src is responsible for activating this mRNA decay pathway. c-Src was recovered with immunoprecipitated PMR1, and it phosphorylates PMR1 in vitro and in vivo. The interaction with c-Src involves two domains of PMR1: Y650 and a series of proline rich SH3 peptides in the N terminus. In cells with little c-Src, PMR1 targeting to polysomes is induced by constitutively active c-Src but not by inactive forms of the kinase. Similarly, only active c-Src induces PMR1-mediated mRNA decay. Finally, we show that EGF rapidly induces c-Src phosphorylation of PMR1, providing a direct link between tyrosine kinase-mediated signal transduction and mRNA decay. PMID- 17349963 TI - The influence of pregnancy on intestinal parasite infection in Thai women. AB - The relationship between pregnancy and both the susceptibility and pathogenicity of parasite infections is disputed. This study compares the prevalence and intensity (as measured by density of eggs in stool samples) of intestinal helminth infections in pregnant and control groups of women from Khon Kaen Province in the northeast of Thailand. Stool samples were taken at the end of the first, second and third trimesters of pregnancy as well as 2 months after parturition and compared for the two groups. There were no significant changes in the prevalence of any of the common helminth species during the course of pregnancy or between the pregnant and control groups. Nor was there any evidence that the density of helminth eggs in the stool samples differed between sample times or between the pregnant and control groups. Our study therefore supports the hypothesis that pregnancy does not influence the course of human infection with helminths. PMID- 17349964 TI - Annexin B1 at the host-parasite interface of the Taenia solium cysticercus: Secreted and associated with inflammatory reaction. AB - Annexin B1 is a novel member of annexin family firstly cloned by immunological screening a Taenia solium cysticercus library. To investigate the histological distribution and physiological role(s) of this protein, we first prepared a specific monoclonal antibody against annexin B1. Western blot analysis indicated that annexin B1 could be detected in cystic fluid of T. solium cysticercus and sera of pigs/humans with cysticercosis. Thus, annexin B1 might belong to the secreted members of annexins. Immunohistochemical analysis revealed that annexin B1 was mainly present in the tegument of bladders, but not in the scolex and neck; it was also detected in the surrounding host-derived layer with granulomatous infiltration. Together with previous, the presented data suggested that the protein inhibited mammalian PLA2 in vitro, and might down regulate host inflammatory responses. PMID- 17349965 TI - Radiative and non-radiative charge recombination pathways in Photosystem II studied by thermoluminescence and chlorophyll fluorescence in the cyanobacterium Synechocystis 6803. AB - The mechanism of charge recombination was studied in Photosystem II by using flash induced chlorophyll fluorescence and thermoluminescence measurements. The experiments were performed in intact cells of the cyanobacterium Synechocystis 6803 in which the redox properties of the primary pheophytin electron acceptor, Phe, the primary electron donor, P(680), and the first quinone electron acceptor, Q(A), were modified. In the D1Gln130Glu or D1His198Ala mutants, which shift the free energy of the primary radical pair to more positive values, charge recombination from the S(2)Q(A)(-) and S(2)Q(B)(-) states was accelerated relative to the wild type as shown by the faster decay of chlorophyll fluorescence yield, and the downshifted peak temperature of the thermoluminescence Q and B bands. The opposite effect, i.e. strong stabilization of charge recombination from both the S(2)Q(A)(-) and S(2)Q(B)(-) states was observed in the D1Gln130Leu or D1His198Lys mutants, which shift the free energy level of the primary radical pair to more negative values, as shown by the retarded decay of flash induced chlorophyll fluorescence and upshifted thermoluminescence peak temperatures. Importantly, these mutations caused a drastic change in the intensity of thermoluminescence, manifested by 8- and 22 fold increase in the D1Gln130Leu and D1His198Lys mutants, respectively, as well as by a 4- and 2.5-fold decrease in the D1Gln130Glu and D1His198Ala mutants, relative to the wild type, respectively. In the presence of the electron transport inhibitor bromoxynil, which decreases the redox potential of Q(A)/Q(A)( ) relative to that observed in the presence of DCMU, charge recombination from the S(2)Q(A)(-) state was accelerated in the wild type and all mutant strains. Our data confirm that in PSII the dominant pathway of charge recombination goes through the P(680)(+)Phe(-) radical pair. This indirect recombination is branched into radiative and non-radiative pathways, which proceed via repopulation of P(680)(*) from (1)[P(680)(+)Ph(-)] and direct recombination of the (3)[P(680)(+)Ph(-)] and (1)[P(680)(+)Ph(-)] radical states, respectively. An additional non-radiative pathway involves direct recombination of P(680)(+)Q(A)( ). The yield of these charge recombination pathways is affected by the free energy gaps between the Photosystem II electron transfer components in a complex way: Increase of DeltaG(P(680)(*)<-->P(680)(+)Phe(-)) decreases the yield of the indirect radiative pathway (in the 22-0.2% range). On the other hand, increase of DeltaG(P(680)(+)Phe(-)<-->P(680)(+)Q(A)(-)) increases the yield of the direct pathway (in the 2-50% range) and decreases the yield of the indirect non radiative pathway (in the 97-37% range). PMID- 17349966 TI - Redox-linked protonation state changes in cytochrome bc1 identified by Poisson Boltzmann electrostatics calculations. AB - Cytochrome bc(1) is a major component of biological energy conversion that exploits an energetically favourable redox reaction to generate a transmembrane proton gradient. Since the mechanistic details of the coupling of redox and protonation reactions in the active sites are largely unresolved, we have identified residues that undergo redox-linked protonation state changes. Structure-based Poisson-Boltzmann/Monte Carlo titration calculations have been performed for completely reduced and completely oxidised cytochrome bc(1). Different crystallographically observed conformations of Glu272 and surrounding residues of the cytochrome b subunit in cytochrome bc(1) from Saccharomyces cerevisiae have been considered in the calculations. Coenzyme Q (CoQ) has been modelled into the CoQ oxidation site (Q(o)-site). Our results indicate that both conformational and protonation state changes of Glu272 of cytochrome b may contribute to the postulated gating of CoQ oxidation. The Rieske iron-sulphur cluster could be shown to undergo redox-linked protonation state changes of its histidine ligands in the structural context of the CoQ-bound Q(o)-site. The proton acceptor role of the CoQ ligands in the CoQ reduction site (Q(i)-site) is supported by our results. A modified path for proton uptake towards the Q(i)-site features a cluster of conserved lysine residues in the cytochrome b (Lys228) and cytochrome c(1) subunits (Lys288, Lys289, Lys296). The cardiolipin molecule bound close to the Q(i)-site stabilises protons in this cluster of lysine residues. PMID- 17349967 TI - Protons bound to the Mn cluster in photosystem II oxygen evolving complex detected by proton matrix ENDOR. AB - Protons in the vicinity of the oxygen-evolving manganese cluster in photosystem II were studied by proton matrix ENDOR. Six pairs of proton ENDOR signals were detected in both the S(0) and S(2) states of the Mn-cluster. Two pairs of signals that show hyperfine constants of 2.3/2.2 and 4.0 MHz, respectively, disappeared after D(2)O incubation in both states. The signals with 2.3/2.2 MHz hyperfine constants in S(0) and S(2) state multiline disappeared after 3 h of D(2)O incubation in the S(0) and S(1) states, respectively. The signal with 4.0 MHz hyperfine constants in S(0) state multiline disappeared after 3 h of D(2)O incubation in the S(0) state, while the similar signal in S(2) state multiline disappeared only after 24 h of D(2)O incubation in the S(1) state. The different proton exchange rates seem to be ascribable to the change in affinities of water molecules to the variation in oxidation state of the Mn cluster during the water oxidation cycle. Based on the point dipole approximation, the distances between the center of electronic spin of the Mn cluster and the exchangeable protons were estimated to be 3.3/3.2 and 2.7 A, respectively. These short distances suggest the protons belong to the water molecules ligated to the manganese cluster. We propose a model for the binding of water to the manganese cluster based on these results. PMID- 17349968 TI - Membrane interaction of islet amyloid polypeptide. AB - Increasing evidence suggests that the misfolding and deposition of IAPP plays an important role in the pathogenesis of type II, or non-insulin-dependent diabetes mellitus (T2DM). Membranes have been implicated in IAPP-dependent toxicity in several ways: Lipid membranes have been shown to promote the misfolding and aggregation of IAPP. Thus, potentially toxic forms of IAPP can be generated when IAPP interacts with cellular membranes. In addition, membranes have been implicated as the target of IAPP toxicity. IAPP has been shown to disrupt membrane integrity and to permeabilize membranes. Since disruption of cellular membranes is highly toxic, such a mechanism has been suggested to explain the observed IAPP toxicity. Here, we review IAPP-membrane interaction in the context of (1) catalyzing IAPP misfolding and (2) being a potential origin of IAPP toxicity. PMID- 17349969 TI - Effect of potassium perfluorooctanesulfonate, perfluorooctanoate and octanesulfonate on the phase transition of dipalmitoylphosphatidylcholine (DPPC) bilayers. AB - Perfluorooctanesulfonic acid (PFOS) is a persistent environmental pollutant that may cause adverse effects by inhibiting pulmonary surfactant. To gain further insights in this potential mechanism of toxicity, we investigated the interaction of PFOS potassium salt with dipalmitoylphosphatidylcholine (DPPC) - the major component of pulmonary surfactant - using steady-state fluorescence anisotropy spectroscopy and DSC (differential scanning calorimetry). In addition, we investigated the interactions of two structurally related compounds, perfluorooctanoic acid (PFOA) and octanesulfonic acid (OS) potassium salt, with DPPC. In the fluorescence experiments a linear depression of the main phase transition temperature of DPPC (T(m)) and an increased peak width was observed with increasing concentration of all three compounds, both using 1,6-diphenyl 1,3,5-hexatriene (DPH) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5 hexatriene p-toluenesulfonate (TMA-DPH) as fluorescent probes. PFOS caused an effect on T(m) and peak width at much lower concentrations because of its increased tendency to partition onto DPPC bilayers, i.e., the partition coefficients decrease in the K(PFOS)>K(PFOA)>>K(OS). Similar to the fluorescence anisotropy measurements, all three compounds caused a linear depression in the onset of the main phase transition temperature and a significant peak broadening in the DSC experiments, with PFOS having the most pronounced effect of the peak width. The effect of PFOS and other fluorinated surfactants on DPPC in both mono- and bilayers may be one mechanism by which these compounds cause adverse biological effects. PMID- 17349970 TI - Facilitating a benign interpretation bias in a high socially anxious population. AB - Previous research has shown that high socially anxious individuals lack the benign interpretation bias present in people without social anxiety. The tendency of high socially anxious people to generate more negative interpretations may lead to anticipated anxiety about future social situations. If so, developing a more benign interpretation bias could lead to a reduction in this anxiety. The current study showed that a benign interpretation bias could be facilitated (or 'trained') in a high socially anxious population. Participants in the benign training groups had repeated practice in accessing benign (positive or non negative) interpretations of potentially threatening social scenarios. Participants in the control condition were presented with the same social scenarios but without their outcomes being specified. In a later recognition task, participants who received benign interpretation training generated more benign, and less negative, interpretations of new ambiguous social situations compared to the control group. Participants who received benign training also predicted that they would be significantly less anxious in a future social situation than those in the control group. Possible implications of the findings for therapeutic interventions in social phobia are discussed. PMID- 17349971 TI - Small GTPase Rho signaling is involved in beta1 integrin-mediated up-regulation of intercellular adhesion molecule 1 and receptor activator of nuclear factor kappaB ligand on osteoblasts and osteoclast maturation. AB - We assessed the characteristics of human osteoblasts, focusing on small GTPase Rho signaling. Beta1 Integrin were highly expressed on osteoblasts. Engagement of beta1 integrins by type I collagen augmented expression of intercellular adhesion molecule 1 (ICAM-1) and receptor activator of nuclear factor kappaB ligand (RANKL) on osteoblasts. Rho was activated by beta1 stimulation in osteoblasts. Beta1 Integrin-induced up-regulation of ICAM-1 and RANKL was inhibited by transfection with adenoviruses encoding C3 transferase or pretreated with Y 27632, specific Rho and Rho-kinase inhibitors. Engagement of beta1 integrin on osteoblasts induced formation of tartrate-resistant acid phosphatase (TRAP) positive multinuclear cells (MNC) in a coculture system of osteoblasts and peripheral monocytes, but this action was completely abrogated by transfection of C3 transferase. Our results indicate the direct involvement of Rho-mediated signaling in beta1 integrin-induced up-regulation of ICAM-1 and RANKL and RANKL dependent osteoclast maturation. Thus, Rho-mediated signaling in osteoblasts seems to introduce major biases to bone resorption. PMID- 17349972 TI - S1P stimulates chemotactic migration and invasion in OVCAR3 ovarian cancer cells. AB - OVCAR3 ovarian cancer cells express three sphingosine 1-phosphate (S1P) receptors, S1P(1), S1P(2), and S1P(3), but not S1P(4). Stimulation of OVCAR3 cells with S1P induced intracellular calcium increases, which were partly inhibited by VPC 23019 (an S1P(1/3) antagonist). S1P-induced calcium increases were mediated by phospholipase C and pertussis toxin (PTX)-sensitive G-proteins in OVCAR3 cells. S1P stimulated extracellular signal-regulated kinase, p38 kinase, and Akt which were inhibited by PTX. S1P-stimulated chemotactic migration of OVCAR3 cells in a PTX-sensitive manner, indicating crucial role of G(i) protein(s) in the process. S1P-induced chemotactic migration of OVCAR3 cells was completely inhibited by LY294002 and SB203580. Pretreatment of VPC 23019 (an S1P(1/3) antagonist) completely inhibited S1P-induced chemotaxis. S1P also induced invasion of OVCAR3 cells, which was also inhibited by VPC 23019. Taken together, this study suggests that S1P stimulate chemotactic migration and cellular invasion, and VPC 23019-sensitive S1P receptor(s) might be involved in the processes. PMID- 17349973 TI - Domains in the XPA protein important in its role as a processivity factor. AB - XPA is a protein essential for nucleotide excision repair (NER) where it is thought to function in damage recognition/verification. We have proposed an additional role, that of a processivity factor, conferring a processive mechanism of action on XPF and XPG, the endonucleases, involved in NER. The present study was undertaken to examine the domain(s) in the XPA gene that are important for the ability of the XPA protein to function as a processivity factor. Using site directed mutagenesis, mutations were created in several of the exons of XPA and mutant XPA proteins produced. The results showed that the DNA binding domain of XPA is critical for its ability to act as a processivity factor. Mutations in both the zinc finger motif and the large basic cleft in this domain eliminated the ability of XPA to confer a processive mechanism of action on the endonucleases involved in NER. PMID- 17349974 TI - Mouse homologue of yeast Prp19 interacts with mouse SUG1, the regulatory subunit of 26S proteasome. AB - Yeast Prp19 has been shown to involve in pre-mRNA splicing and DNA repair as well as being an ubiquitin ligase. Mammalian homologue of yeast Prp19 also plays on similar functional activities in cells. In the present study, we isolated mouse SUG1 (mSUG1) as binding partner of mouse Prp19 (mPrp19) by the yeast two-hybrid system. We confirmed the interaction of mPrp9 with mSUG1 by GST pull-down assay and co-immunoprecipitation assay. The N-terminus of mPrp19 including U-box domain was associated with the C-terminus of mSUG1. Although, mSUG1 is a regulatory subunit of 26S proteasome, mPrp19 was not degraded in the proteasome-dependent pathway. Interestingly, GFP-mPrp19 fusion protein was co-localized with mSUG1 protein in cytoplasm as the formation of the speckle-like structures in the presence of a proteasome inhibitor MG132. In addition, the activity of proteasome was increased in cells transfected with mPrp19. Taken together, these results suggest that mPrp19 involves the regulation of protein turnover and may transport its substrates to 26S proteasome through mSUG1 protein. PMID- 17349975 TI - Hepatocyte growth factor at S phase induces G2 delay through sustained ERK activation. AB - The effect of growth factors on the cell cycle progression, except G1/S transition, is poorly understood. Herein, we examined the effect of hepatocyte growth factor (HGF) treated at S phase on the cell cycle progression of HeLa cells. Interestingly, the treatment resulted in G2 delay, evidenced by flow cytometric and mitotic index analyses. The delay corresponded with the delay of degradation of cyclin A and cyclin B, and the delay of decrease of Cdk1/cyclin B and Cdk2/cyclin A kinase activities. As for the signaling responsible, sustained activation of ERK, but neither of p38MAPK nor of JNK, was observed after HGF treatment at S phase. Furthermore, U0126, an inhibitor of MEK1, and DN-MEK partially abrogated the G2 delay, indicating that activation of MEK-ERK pathway is involved. Taken together, HGF treatment of HeLa cells at S phase induces G2 delay partially through sustained activation of ERK signaling. PMID- 17349976 TI - ROS mediate the hypoxic repression of the hepcidin gene by inhibiting C/EBPalpha and STAT-3. AB - Hepcidin, a liver peptide, systemically inhibits iron utilization and is downregulated under hypoxic conditions. However, little is known about the mechanism underlying the hypoxic suppression of hepcidin. Here, we tested the possibility that HIF-1 and ROS are involved in hepcidin regulation. Hepcidin mRNA, pre-mRNA, and protein levels were reduced in mouse livers and in HepG2 cells after hypoxic incubation, and HIF-1 overexpression and knock-down studies showed that hepcidin regulation is independent of HIF-1. On the other hand, ROS levels were significantly elevated in hypoxic HepG2 cells, and anti-oxidants prevented the hypoxic down-regulation of hepcidin. Conversely, a prooxidant, H(2)O(2), suppressed hepcidin expression in these cells even in normoxia. Of the various transcription factors examined, C/EBPalpha and STAT-3 were found to dissociate from hepcidin promoter under hypoxia, but to become fully engaged after anti-oxidant treatment. These results suggest that ROS repress the hepcidin gene by preventing C/EBPalpha and STAT-3 binding to hepcidin promoter during hypoxia. PMID- 17349977 TI - Design of 5'-untranslated region variants for tunable expression in Escherichia coli. AB - Redesign or modification of the cellular physiology requires a quantitatively well-controlled expression system known as the "tunable expression." Although the modification of promoters demonstrates the great impact on the translation efficiency, it is difficult to detect the proper variants required for tunable expression. The 5'-untranslated region (UTR), however, can be an important target for tunable expressions because the ribosome binding affinity is directly modulated by the sequence variants of the Shine-Dalgarno (SD) sequence and the AU rich sequence, which are the ribosome binding sites and a SD-sequence-independent translation enhancer, respectively. This study developed a simple method to obtain numerous 5'-UTR variants and analyze their translation efficiency based on the PCR-based site-directed mutagenesis and the expressional PCR using coupled in vitro transcription/translation system derived from Escherichia coli and eGFP gene as a template. SD sequence variants (18) and AU-rich sequence variants (36), which have a wide range of relative expression levels ranging from 0.1 to 2.0, were obtained. The translation efficiency was affected by the ribosome binding affinity and its accessibility that is dependent on the secondary structure around the 5'-UTR. PMID- 17349978 TI - Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism. AB - Autism is a severe neurodevelopmental disorder defined by social and communication deficits and ritualistic-repetitive behaviors that are detectable in early childhood. Brain-derived neurotrophic factor (BDNF) plays a critical role in the pathogenesis of autism. In this study, we examined the SNP- and haplotypic-association of BDNF with autism in a trios-based association study (the Autism Genetic Resource Exchange). We also examined the expression of BDNF mRNA in the peripheral blood lymphocytes of drug-naive autism patients and control subjects. In the TDT of autism trios, the SNP haplotype combinations showed significant associations in the autism group. BDNF expression in the drug naive autistic group was found to be significantly higher than in the control group. We suggest that BDNF has a possible role in the pathogenesis of autism through its neurotrophic effects on the serotonergic system. PMID- 17349979 TI - Biochemical characterization of the type I inositol polyphosphate 4-phosphatase C2 domain. AB - Inositol polyphosphate 4 phosphatases (IP4Ps) are enzymes involved in the regulation of phosphoinositide 3-kinase lipid signaling. They catalyze the hydrolysis of the 4-position phosphate from phosphatidylinositol 3,4-bisphosphate to phosphatidylinositol 3-phosphate. In this paper we have characterized a lipid binding C2 domain located on the N-terminus of type I IP4Ps. Mutational analysis of the lipid binding loops suggests that Asp61, Asp120, Asp123, Lys122, Arg124 are involved in lipid binding in vitro. In addition, we show that this C2 domain binds calcium but calcium is not involved in lipid binding. This paper provides insight into the mechanism of membrane interaction of IP4Ps. PMID- 17349980 TI - The fate of "dark" neurons produced by transient focal cerebral ischemia in a non necrotic and non-excitotoxic environment: neurobiological aspects. AB - BACKGROUND INFORMATION: We recently proposed novel neurobiological ideas for discussion regarding the common nature (malfunction of a physicochemical phenomenon genetically programmed for the morphological execution of ontogenetic apoptosis), mechanism of formation (phase transition in an intraneuronal gel structure) and mode of death (neither necrosis nor apoptosis) of "dark" neurons. These ideas were deduced from morphological changes in neurons found in a visually undamaged environment after in vivo or postmortem mechanical or electric injuries and after hypoglycemia. OBJECTIVE: In search of further support, this paper revisits these ideas in the case of transient focal cerebral ischemia by investigating the light- and electron-microscopic changes produced in neurons by a 1-h occlusion of the rat middle cerebral artery in non-necrotic and non excitotoxic tissue areas, where extraneuronal pathological processes may not influence the intraneuronal events. RESULTS: In the first hour after restoration of circulation, the soma-dendrite domains of "dark" neurons displayed hyperbasophilia, hyperargyrophilia, hyper-electron density and a dramatic compaction of ultrastructural elements. Between 1 h and 1 day of the restored circulation, the degree of ultrastructural compaction decreased and mitochondrion derived membranous whorls appeared in several "dark" neurons indicating recovery. Further, the cytoplasm of scattered neurons manifesting the apoptotic condensation pattern of the nuclear chromatin displayed the same morphological features as those of the freshly produced "dark" neurons. After 1 day of restored circulation, both the non-recovering "dark" neurons and the apoptotic neurons fell into membrane-bound, compact and electron-dense fragments, which were subsequently engulfed by phagocytotic cells. CONCLUSION: These observations support each of the ideas mentioned above. PMID- 17349981 TI - Familial Alzheimer's disease presenilin 1 mutation M146V increases gamma secretase cutting of p75NTR in vitro. AB - The cholinergic neurons of the basal forebrain are amongst the first to degenerate in Alzheimer's disease. These neurons are unique in the brain, expressing the tyrosine kinase receptor TrkA, together with the common neurotrophin receptor p75NTR; both of which bind nerve growth factor. Activation of the TrkA receptor is important in the maintenance of cell viability, whereas the p75NTR receptor has been implicated in apoptosis. Mutations in the gene for presenilin 1, a multi-transmembrane aspartyl protease, are known to cause familial Alzheimer's disease. This is thought to be due to their effect on gamma secretase-dependent processing of amyloid precursor protein and subsequent formation of amyloid. Since p75NTR was recently shown to undergo gamma-secretase regulated intramembrane proteolysis, this study examines the effect of familial Alzheimer mutations on processing of p75NTR. PC12 cells were stably transfected with familial mutations M146V, A246E and deltaE9 and wild-type presenilin 1 and were examined here for gamma-secretase-dependent proteolysis of p75NTR. Overexpression of wild-type presenilin 1 did not increase gamma-secretase mediated cleavage of p75NTR. However, by contrast, the presence of the M146V mutation was shown to significantly increase cleavage of p75NTR compared with the other mutations. Survival of cholinergic neurons will depend on the balance between the receptors TrkA and p75NTR, and their respective signalling pathways. Thus alterations in p75NTR proteolysis may influence this equilibrium. The novel finding that a mutation may increase processing of p75NTR may have implications for the pathogenic outcome in Alzheimer's disease. PMID- 17349982 TI - 5-Lipoxygenase inhibitor MK-886 increases GluR1 phosphorylation in neuronal cultures in vitro and in the mouse cortex in vivo. AB - Modifications of AMPA glutamate receptor GluR1 phosphorylation are critical for neuroplastic mechanisms. Previous in vitro studies in brain slices employed MK 886, a functional inhibitor of the enzyme 5-lipoxygenase (5-LOX), and found increased GluR1 phosphorylation. Since slice preparations have accompanying postmortem phosphorylation changes, e.g., decreased GluR1 phosphorylation, it remains to be clarified whether MK-886 can affect GluR1 phosphorylation in intact neurons and in the brain in vivo. We used primary neuronal cultures prepared from embryonic mouse brain and in vivo drug administration to investigate the effects of MK-886 on GluR1 phosphorylation using quantitative Western immunoblotting assays. In vitro, MK-886 increased GluR1 phosphorylation at both serine 831 and serine 845. In vivo, repeated but not a single MK-886 injection increased GluR1 phosphorylation in the prefrontal cortex. These findings indicate that MK-886 has an intrinsic effect on neuronal phosphorylation both in vitro and in vivo and support the use of MK-886 as a pharmacological tool in studies of not only the 5 LOX pathway but also neuronal GluR1 functioning. PMID- 17349983 TI - Brain and cognitive processes of imitation in bimanual situations: Making inferences about mirror neuron systems. AB - The relationship between mirror neuron systems and imitation is being widely studied. However, most if not all, studies on imitation have investigated only the mirror mode. The present study examined whether imitation in a mirror (specular) mode is likely to reflect similar or distinct neural processes and psychological principles as imitation in a non-mirror (anatomical) mode. Experiment 1 examined whether altering sensory information may reverse the typical mirror mode advantage, resulting in superior performance in the non mirror mode. Experiment 2 examined whether the two different modes of imitation rely differentially on target selection (goals) and effector selection (means). Experiment 3 examined whether spatial translations are likely to occur in a typical non-mirror imitation mode. Experiment 4 examined whether non-mirror imitation would be the naturally selected mode of imitation under some situations. Findings from all experiments demonstrated marked differences between mirror and non-mirror modes of imitation. The implications of these findings may raise challenges for theories and models of mirror neurons. PMID- 17349984 TI - Understanding the role of transforming growth factor-beta1 in intimal thickening after vascular injury. AB - Intimal thickening is the most important cause of in-stent restenosis. The pathology of intimal thickening is attributable to a local inflammatory response after vascular injury which results in the production of cytokines. Transforming growth factor-beta1 (TGF-beta1) is a profibrotic cytokine that is involved in the induction of intimal thickening. Up-regulation of TGF-beta1 after arterial injury results in the activation of various downstream pathways which stimulate the proliferation and migration of vascular smooth muscle cells, as well as the production of local extracellular matrix proteins. Recent evidence suggests that antagonizing TGF-beta1 activity with direct or indirect inhibitors may attenuate or prevent intimal thickening. Additionally, TGF-beta1 synthesis, activation and downstream regulation may also serve as significant sources of treatment. This review attempts to show the role of TGF-beta1 in the pathology of intimal thickening and underlines the importance of TGF-beta1 as a target for therapy. PMID- 17349985 TI - Alteration of DMBA-induced oxidative stress by additive action of a modified indigenous preparation--Kalpaamruthaa. AB - The present study investigated the protective efficacy of the novel preparation named as Kalpaamruthaa (KA, includes Semecarpus anacardium Linn nut milk extract (SA), dried powder of Phyllanthus emblica fruit and honey) on the peroxidative damage and abnormal antioxidant levels in the hepatic mitochondrial fraction of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma rats. Female Sprague-Dawley rats of weight 180+/-10 g were categorized into six groups. Three groups were administered DMBA (25 mg/rat dissolved in olive oil, orally) to induce mammary carcinoma. One of these groups received KA treatment (300 mg/kg b.wt., orally) and other group received SA (200 mg/kg b.wt., orally) for 14 days after 90 days of DMBA induction. Vehicle-treated control and drug control groups were also included. The hepatic mitochondrial fraction of untreated DMBA rats showed 2.96-fold increase in MDA content when compared to control rats and abnormal changes in the activities/levels of mitochondrial enzymic (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzymic (glutathione, vitamin C and vitamin E) antioxidants were observed. DMBA-treated rats also showed decline in the activities of mitochondrial enzymes such as succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase. In contrast, rats treated with SA and KA showed normal lipid peroxidation antioxidant defenses and mitochondrial enzymes, thereby showing the protection rendered by SA and KA. Although, KA treatment exhibited more profound effect in inhibiting DMBA-induced oxidative stress than sole SA treatment. Results of the study indicate that the anticarcinogenic activity of KA during DMBA-initiated mammary carcinogenesis is mediated through alteration of hepatic antioxidant status as well as modulation of TCA cycle enzymes. On the basis of the observed results, KA can be considered as a readily accessible, promising and novel cancer chemopreventive agent. PMID- 17349986 TI - Lipid, haemostatic and inflammatory variables in relation to the estrogen receptor alpha (ESR1) PvuII and XbaI gene polymorphisms. AB - BACKGROUND: Estrogen is known to affect lipoprotein metabolism, the haemostatic system and inflammatory markers. Our aim was to determine whether estrogen receptor alpha (ESR1) PvuII and XbaI gene polymorphisms can influence lipid, haemostatic and inflammatory variables in healthy Caucasian women and men of reproductive age. METHODS: 58 healthy women (aged between 18 and 45 years) and 55 healthy men (aged between 21 and 45 years) of reproductive age were enrolled in our study. FSH levels, lipid (total cholesterol, triglyceride, HDL cholesterol, lipoprotein(a), apo A-I, apo B), haemostatic (prothrombin time, activated partial thromboplastin time (aPTT), thrombin time, fibrinogen, factor V, VII, VIII, protein C, protein S, antithrombin III) and inflammatory (CRP) variables were measured on autoanalyzers using commercially available kits. Serum VLDL and LDL cholesterol concentrations were calculated with the equation of Friedewald. The ESR1 PvuII and XbaI genotypes were determined with PCR-RFLP method. RESULTS: In the total group, the ESR1 XbaI GG genotype carriers had significantly higher serum lipoprotein(a) concentrations than the AA or AG genotype carriers. Serum total cholesterol concentrations were significantly higher in healthy women with the PvuII CC genotype than in those with the TT or TC genotypes, whereas healthy women with the GG genotype of the ESR1 XbaI polymorphism had significantly higher serum total cholesterol and LDL cholesterol levels compared to those with the AA or AG genotypes. No other effects of the ESR1 PvuII and XbaI polymorphisms were found on the investigated lipid, haemostatic and inflammatory variables either in the total group or in women and men separately. CONCLUSIONS: The ESR1 PvuII and XbaI gene polymorphisms seem to affect lipoprotein metabolism in healthy subjects of peak reproductive age. However, further studies are needed to determine the molecular mechanisms by which the two polymorphisms could influence serum lipid levels. PMID- 17349987 TI - Hepatic surgery-related hypophosphatemia. AB - This review describes pathophysiology of post-surgical hypophosphatemia (HP), which has particularly high incidence following liver transplantation. HP remains poorly understood; and there is a lack of universally accepted guidelines for its investigation and management. The pathogenesis of HP following major liver surgery has been hypothesized as being due either to excessive utilization by regenerating liver or increased urinary losses of phosphate. This review provides evidence that excessive urinary loss rather than increased Pi uptake by the liver is the most likely mechanism, and this may be mediated by recently described phosphaturic factors, known as phosphatonins. Until recently blood Pi homeostasis had been explained solely in terms of classical hormones, i.e., vitamin D and PTH. It is however increasingly recognized that phosphatonins may play a critical role in the post-operative HP, but the exact mechanism and candidate phosphaturic factor has not yet been identified. In this review, we have described likely mechanisms and suggest candidate phosphatonins that may mediate urinary Pi loss following liver transplantation. We also discuss the biochemical consequences of cellular Pi depletion, which exposes some gaps in the utilization of established knowledge and therefore in the management of HP. The main aspects of pathophysiology of HP and cellular Pi depletion are presented to provide rational for novel biochemical investigations, which are likely to improve monitoring of HP associated metabolic stress as well as extent of severity of HP, and thereby enhance management of these patients. PMID- 17349988 TI - Characterization of plasma protein profiles from patients with neurofibromatosis I. AB - BACKGROUND: Neurofibromatosis type I (NF1) is a common autosomal dominant disorder, affecting approximately one in every 3500 individuals. Early diagnosis of NF1 can be ambiguous, and clinical symptoms are diverse. We compared plasma protein profiles between normal controls and NF1 patients for yielding important insights into the mechanisms underlying NF1 related tumor formation and diagnostic biomarkers to classify the diverse clinical symptoms. METHODS: MALDI TOF mass spectrometry was used to identify plasma proteins. Prior to that, a micro-solution isoelectric focusing (microsol-IEF) pre-fractionation combined with two-dimensional gel electrophoresis (2-DE) using the narrow pH range strip was applied to enhance the resolution and sensitivity. RESULTS: There was a significant increase in fibrinogen level in patients with NF1. This increase in fibrinogen expression was subsequently confirmed by Western blotting assay. Furthermore, the effect of fibrinogen on cell growth was tested on PC12 cells. CONCLUSION: Fibrinogen is the central protein associated with angiogenesis; a process which modulates tumor growth, the up-regulation of fibrinogen may help explain the development of neurofibromas in NF1 patients. PMID- 17349989 TI - Parathyroidectomy monitored by intra-operative PTH: the relevance of the 20 min end-point. AB - OBJECTIVES: RI-PTH measurements are a prerequisite for minimally invasive parathyroidectomy, providing guidance regarding the removal of hyper-functioning tissue. Different criteria of PTH decrease, concentration and clearance were analyzed in order to predict surgical treatment. DESIGN AND METHODS: Blood samples at pre-incision, manipulation, 5, 10 and 20 min after resection, were collected from 145 patients presenting unambiguous, pre-surgical "single adenoma" diagnosis. RESULTS: The meeting of Irvin criterion would have permitted the identification of 28% uncured cases leading to 4% unnecessary neck exploration. On the contrary, we would have identified all of the uncured patients, to the detriment of 7% unnecessarily prolonged procedure by taking into account PTH drop, concentration and clearance shape at 20 min. CONCLUSIONS: The 20' end-point plays a key role in the correct determination of surgical outcome, strongly improving the possibility of adequate patient treatment. However, since the high success rate of traditional parathyroidectomy, yet not provided by RI-PTH, the utmost improvement to hyper-parathyroidism surgical treatment by RI-PTH could be achieved in pre-operative equivocal glands localization or multiglandular disease selected population to quickly guide and confirm the complete removal of all hyper-secreting tissue. PMID- 17349990 TI - False recollection in children with reading comprehension difficulties. AB - Children with reading comprehension difficulties display impaired performance on semantic processing tasks. These impairments are assumed to reflect weaker knowledge about abstract semantic associations between words in poor comprehenders [Nation, K., and Snowling, M. (1999). Developmental differences in sensitivity to semantic relations among good and poor comprehenders: evidence from semantic priming. Cognition, 19, B1-B13.]. We examined the performance of poor comprehenders on the Deese/Roediger/McDermott (DRM) paradigm. Children studied spoken words that were semantic associates (e.g., bed, rest, and awake) or phonological associates (e.g., pole, bowl, and hole) followed by free recall and a recognition test containing nonstudied critical words (e.g., sleep and roll). Results showed reduced recall and recognition of critical words in the semantic condition but not in the phonological condition for poor comprehenders. We argue that poor comprehenders are less sensitive to abstract semantic associations between words because of reduced gist memory. PMID- 17349991 TI - Tissue-specific changes in glutathione content of hypoxic newborn pigs reoxygenated with 21% or 100% oxygen. AB - We compared the responses towards oxidative stress in the liver, lung, brain, heart, kidney and small intestine of hypoxic newborn animals resuscitated with 21% or 100% oxygen. After stabilization, piglets (1-3 days, 1.6-2.0 kg, n=8/group) were randomized to receive 2 h of alveolar hypoxia (FiO(2)=0.10-0.14) followed by reoxygenation with 21% or 100% oxygen for 1 h and then another hour with 21% oxygen. Controls were sham-operated without hypoxia-reoxygenation. At the end of the experiment, tissues from liver, lung, brain, heart, kidney and small intestine were collected and tested for GSH, GSSG and lipid peroxidation levels and histological examination. In normoxic controls, liver had the highest GSH level, followed by brain, heart, lung, small intestine and kidney which had the highest level of oxidative stress markers (GSSG level and GSSG:GSH ratio). Hypoxic-reoxygenated piglets had the highest GSSG levels and GSSG:GSH ratio in the kidney. Hypoxic piglets resuscitated with 100% oxygen had higher GSSG:GSH ratios in the lung and liver, but not in the kidney, brain, heart and small intestine, than controls, which were not different from the 21% group. No significant differences in peroxidation and histological tissue damage were found between groups in the liver and lung. We concluded that although hypoxic piglets resuscitated with 100% oxygen have higher oxidative stress in the liver and lung than with 21% oxygen, there are no significant differences in peroxidation and histological tissue damage acutely. PMID- 17349992 TI - 3,5-dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7): a new multidrug resistance inhibitor devoid of effects on Langendorff-perfused rat heart. AB - Cardiac effects of 3,5-dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6 dimethylpyridine (DP7), a novel multidrug resistance (MDR) inhibitor, in Langendorff-perfused rat heart have been investigated and compared to that of nifedipine. Nifedipine decreased concentration-dependently (IC50=8.89+/-1.09x10( 8) M) left ventricular pressure leaving unaltered coronary perfusion pressure, whereas DP7 did not affect both parameters. Nifedipine did not modify both QRS and QT intervals of electrocardiogram (ECG). Second-degree atrioventricular block or ventricular rhythm occurred in presence of nifedipine, however, in 4 out of 6 hearts. DP7, up to 30 microM, failed to alter ECG parameters. In conclusion, DP7, may represent a lead compound for the development of potent dihydropyridine MDR chemosensitizers devoid of cardiac effects. PMID- 17349993 TI - Suppressive effect of a novel water-soluble artemisinin derivative SM905 on T cell activation and proliferation in vitro and in vivo. AB - Artemisinin and its derivatives exhibit potent immunosuppressive activity. The aim of this study was to investigate the suppressive effects of SM905, a new water-soluble artemisinin derivative, on T lymphocytes both in vitro and in vivo, and explore its potential mode of action. The results showed that SM905 had a high inhibitory activity in Concanavalin A (ConA)-induced splenocyte proliferation and mixed lymphocyte reaction, and a relatively low cytotoxicity in vitro. In ovalbumin-immunized mice, oral administration of SM905 dose-dependently suppressed T cell proliferative response to ovalbumin, and inhibited anti ovalbumin interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production by T cells. Further studies showed that SM905 inhibited TCR (T cell receptor)/CD3 plus CD28-mediated primary T cell proliferation and cytokine production (IL-2 and IFN gamma), and exerted an inhibitory action on the phosphorylation of mitogen activated protein (MAP) kinases including extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal kinase (JNK), and the activation of Ras. The results of this study provided experimental evidence that the new artemisinin derivative SM905 had immunosuppressive effects both in vitro and in vivo. SM905 suppressed T cell activation, which was associated with the inhibition of MAP kinases and Ras activation. Our results suggested a potential of SM905 to be developed as a new type agent for treating T cell-mediated immune disorder. PMID- 17349994 TI - mGlu5 receptor and protein kinase C implicated in the development and induction of neuropathic pain following chronic ethanol consumption. AB - The central mechanisms of neuropathic pain following chronic ethanol consumption are poorly understood. We previously reported that the levels of metabotropic glutamate 5 (mGlu5) receptor and phosphorylated-protein kinase C (PKC) were significantly increased in the spinal cord following chronic ethanol consumption. The aim of this study was to investigate whether mGlu5 receptor and PKC inhibitors directly attenuate the neuropathic pain-like state induced by chronic ethanol treatment in rats. A significant decrease in the mechanical nociceptive threshold was observed 5 weeks of chronic ethanol consumption. This hyperalgesia was significantly attenuated by repeated i.p. injection of (S)-2,6-diamino-N-[[1 (oxotridecyl)-2-piperidinyl]methyl] hexanamide dihydrochloride (NPC15437), a selective PKC inhibitor, once a day for a week after 4 weeks of ethanol treatment. Furthermore, this hyperalgesia was also significantly attenuated by repeated i.p. injection of 6-methyl-2-[phenylethynyl]-pyridine (MPEP), a selective mGlu5 receptor inhibitor, once a day for a week after 4 weeks of ethanol treatment. Furthermore, the hyperalgesia that developed after 5 weeks of ethanol treatment was significantly suppressed by a single i.p. post-injection with either NPC15437 or MPEP. These findings constitute direct evidence that spinal mGlu5 receptor and PKC play substantial roles in the development and maintenance of an ethanol-dependent neuropathic pain-like state in rats. PMID- 17349995 TI - Involvement of the sigma1 receptor in inhibiting activity of fluvoxamine on marble-burying behavior: comparison with paroxetine. AB - In the present study, we examined the involvement of the sigma1 receptor in the inhibitory effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine, compared with that of paroxetine, on marble-burying behavior, which is an animal model of obsessive-compulsive disorder. Sigma1 receptor agonists (+) SKF 10047 and PRE-084 significantly inhibited marble-burying behavior. Sigma receptor antagonist BD 1047 and selective sigma1 receptor antagonist BD 1063 significantly attenuated the inhibition of marble-burying behavior by fluvoxamine. In contrast, selective sigma2 receptor antagonist SM-21 failed to affect the inhibition of marble-burying behavior by fluvoxamine. On the other hand, BD 1047 and BD 1063 had no effect on the inhibition of marble-burying behavior by paroxetine. These observations show that activation of the sigma1 receptor is a necessary component in the inhibitory effect of fluvoxamine on marble-burying behavior, and that the mechanism of its action is clearly different from that of paroxetine. PMID- 17349997 TI - Comparison of cell interactions with laser machined micron- and nanoscale features in polymer. AB - Control of cell responses to artificial surfaces is a research goal for much of the biomaterials community. The role that the micron scale topography of a surface can play in controlling cell responses has been well documented and recent advances in nanofabrication techniques have lead to an interest in cells' responses to submicron-scale surface features. The study described here compares the relative influences that nanoscale and micron-scale features exert on cells by examining cytoskeletal organisation. Micron-scale structures were generated on the polyamide Kapton using a 193 nm ArF Excimer laser, at 400 mJ/cm2 fluence. Nanoscale features were generated on Kapton using the excimer laser with a phase mask. Osteoblasts were seeded onto surfaces for 24 h, then the cell membranes were detergent-extracted, and the cells were applied with a primary antibody to actin and a colloidal gold-conjugated secondary antibody. Samples to be examined using the confocal were mounted in glycerol, those for electron microscopy were carbon-coated. The organisation of actin was examined on micron- and nano-scale structures by scoring sections for order of branching and angles of branching to relate changes in the cytoskeleton relative to the control. Although there was a strong influence of micron-scale structures, the cytoskeleton of cells on the nanoscale structures were similar to the controls. PMID- 17349996 TI - Opioid agonist efficacy predicts the magnitude of tolerance and the regulation of mu-opioid receptors and dynamin-2. AB - It has been proposed that opioid agonist efficacy may play a role in tolerance and the regulation of opioid receptor density. To address this issue, the present studies estimated the in vivo efficacy of three opioid agonists and then examined changes in spinal mu-opioid receptor density following chronic treatment in the mouse. In addition, tolerance and regulation of the trafficking protein dynamin-2 were determined. To evaluate efficacy, the method of irreversible receptor alkylation was employed and the efficacy parameter tau estimated. Mice were injected with the irreversible mu-opioid receptor antagonist clocinnamox (0.32 25.6 mg/kg, i.p), and 24 h later, the analgesic potency of s.c. morphine, oxycodone and etorphine were determined. Clocinnamox dose-dependently antagonized the analgesic effects of morphine, etorphine and oxycodone. The shift to the right of the dose-response curves was greater for morphine and oxycodone compared to etorphine and the highest dose of clocinnamox reduced the maximal effect of morphine and oxycodone, but not etorphine. The order of efficacy calculated from these results was etorphine>morphine>oxycodone. Other mice were infused for 7 days with oxycodone (10-150 mg/kg/day, s.c.) or etorphine (50-250 microg/kg/day, s.c.) and the analgesic potency of s.c. morphine determined. The low efficacy agonist (oxycodone) produced more tolerance than the high efficacy agonist (etorphine) at equi-effective infusion doses. In saturation binding experiments, the low efficacy opioid agonists (morphine, oxycodone) did not regulate the density of spinal mu-opioid receptors, while etorphine produced approximately 40% reduction in mu-opioid receptor density. Furthermore, etorphine increased spinal dynamin-2 abundance, while oxycodone did not produce any significant change in dynamin-2 abundance. Overall, these data indicate that high efficacy agonists produce less tolerance at equi-effective doses. Furthermore, increased efficacy was associated with mu-opioid receptor downregulation and dynamin-2 upregulation. Conversely, lower efficacy agonists produced more tolerance at equi-effective doses, but did not regulate mu-opioid receptor density or dynamin-2 abundance. Taken together, these studies indicate that agonist efficacy plays an important role in tolerance and regulation of receptors and trafficking proteins. PMID- 17349998 TI - Human Misato regulates mitochondrial distribution and morphology. AB - Misato of Drosophila melanogaster and Saccharomyces cerevisiae DML1 are conserved proteins having a homologous region with a part of the GTPase family that includes eukaryotic tubulin and prokaryotic FtsZ. We characterized human Misato sharing homology with Misato of D. melanogaster and S. cerevisiae DML1. Tissue distribution of Misato exhibited ubiquitous distribution. Subcellular localization of the protein studied using anti-Misato antibody suggested that it is localized to the mitochondria. Further experiments of fractionating mitochondria revealed that Misato was localized to the outer membrane. The transfection of Misato siRNA led to growth deficiencies compared with control siRNA transfected HeLa cells, and the Misato-depleted HeLa cells showed apoptotic nuclear fragmentation resulting in cell death. After silencing of Misato, the filamentous mitochondrial network disappeared and fragmented mitochondria were observed, indicating human Misato has a role in mitochondrial fusion. To examine the effects of overexpression, COS-7 cells were transfected with cDNA encoding EGFP-Misato. Its overexpression resulted in the formation of perinuclear aggregations of mitochondria in these cells. The Misato-overexpressing cells showed low viability and had no nuclei or a small and structurally unusual ones. These results indicated that human Misato has a role(s) in mitochondrial distribution and morphology and that its unregulated expression leads to cell death. PMID- 17349999 TI - Zinc transporter 2 (SLC30A2) can suppress the vesicular zinc defect of adaptor protein 3-depleted fibroblasts by promoting zinc accumulation in lysosomes. AB - Zinc accumulation in the lumen of cytoplasmic vesicles is one of the mechanisms by which cells can store significant amounts of this essential but potentially toxic biometal. Previous studies had demonstrated reduced vesicular zinc levels in fibroblasts from mutant mice deficient in adaptor protein 3 (AP-3), a complex involved in protein trafficking to late endosomes and lysosomes. We have observed a similar phenotype in the human fibroblastoid cell line, M1, upon small interference RNA-mediated AP-3 knockdown. A survey of the expression and localization of zinc transporter (ZnT) family members identified ZnT2, ZnT3, and ZnT4 as likely mediators of vesicular zinc accumulation in M1 cells. Expression of green fluorescence protein (GFP)-tagged ZnT2 and ZnT3 promoted accumulation of vesicular zinc as visualized using the indicator zinquin. Moreover, GFP-ZnT2 overexpression elicited a significant accumulation of zinc within mature lysosomes, which in untransfected M1 cells contained little or no chelatable zinc, and restored the zinc storage capability of AP-3-deficient cells. These results suggest that ZnT2 can facilitate vesicular zinc accumulation independently of AP-3 function, and validate the M1 fibroblastoid line as a human cell culture system amenable to the study of vesicular zinc regulation using techniques compatible with functional genomic approaches. PMID- 17350000 TI - The SUF iron-sulfur cluster biosynthetic machinery: sulfur transfer from the SUFS SUFE complex to SUFA. AB - Iron-sulfur cluster biosynthesis depends on protein machineries, such as the ISC and SUF systems. The reaction is proposed to imply binding of sulfur and iron atoms and assembly of the cluster within a scaffold protein followed by transfer of the cluster to recipient apoproteins. The SufA protein from Escherichia coli, used here as a model scaffold protein is competent for binding sulfur atoms provided by the SufS-SufE cysteine desulfurase system covalently as shown by mass spectrometry. Investigation of site-directed mutants and peptide mapping experiments performed on digested sulfurated SufA demonstrate that binding exclusively occurs at the three conserved cysteines (cys50, cys114, cys116). In contrast, it binds iron only weakly (K(a)=5 x 10(5)M(-1)) and not specifically to the conserved cysteines as shown by Mossbauer spectroscopy. [Fe-S] clusters, characterized by Mossbauer spectroscopy, can be assembled during reaction of sulfurated SufA with ferrous iron in the presence of a source of electrons. PMID- 17350001 TI - Plastid division coordination across a double-membraned structure. AB - Chloroplasts still retain components of the bacterial cell division machinery and research over the past decade has led to an understanding of how these stromal division proteins assemble and function as a complex chloroplast division machinery. However, during evolution plant chloroplasts have acquired a number of cytosolic division proteins, indicating that unlike the cyanobacterial ancestors of plastids, chloroplast division in higher plants require a second division machinery located on the chloroplast outer envelope membrane. Here we review the current understanding of the stromal and cytosolic plastid division machineries and speculate how two protein machineries coordinate their activities across a double-membraned structure. PMID- 17350002 TI - Identification by surface plasmon resonance of the mycobacterial lipomannan and lipoarabinomannan domains involved in binding to CD14 and LPS-binding protein. AB - The mycobacterial lipoglycans, lipomannan (LM) and lipoarabinomannan (LAM), regulate host defence mechanisms through their interaction with pattern recognition receptors such as Toll-like receptors (TLRs). We have developed a surface plasmon resonance assay to analyse the molecular basis for the recognition of Mycobacterium kansasii LM or LAM, by immobilized CD14 and LPS binding protein (LBP) both being capable to promote presentation of bacterial glycolipids to TLRs. The affinity of either LM/LAM was higher to CD14 than to LBP. Kinetic and Scatchard analyses were consistent with a model involving a single class of binding sites. These interactions required the lipidic anchor, but not the carbohydrate domains, of LM or LAM. We also provide evidence that addition of recombinant LBP enhanced the stimulatory effect of LM or LAM on matrix metalloproteinase-9 expression and secretion in macrophages, through a TLR1/TLR2-dependent mechanism. PMID- 17350003 TI - FurA modulates gene expression of alr3808, a DpsA homologue in Nostoc (Anabaena) sp. PCC7120. AB - The DNA-binding protein from stationary phase (Dps) protein family plays an important role in protecting microorganisms from oxidative and nutritional stresses. In silico analysis of the promoter region of alr3808, a dpsA homologue from the cyanobacterium Nostoc sp. PCC7120 shows putative iron-boxes with high homology with those recognized by FurA (ferric uptake regulator). Evidence for the modulation of dpsA by FurA was obtained using in vitro and in vivo approaches. SELEX linked to PCR was used to identify P(dpsA) as a FurA target. Concurrently, EMSA assays showed high affinity of FurA for the dpsA promoter region. DpsA expression analysis in an insertional mutant of the alr1690 alphafurA message (that exhibited an increased expression of FurA) showed a reduced synthesis of DpsA. These studies suggest that FurA plays a significant role in the regulation of the DpsA. PMID- 17350004 TI - Overexpression of pitx3 upregulates expression of BDNF and GDNF in SH-SY5Y cells and primary ventral mesencephalic cultures. AB - The transcription factor Pitx3 plays an important role in the development of midbrain to promote the growth and differentiation of dopamine neurons. The present study has demonstrated that overexpression of Pitx3 in SH-SY5Y cells and primary ventral mesencephalic (VM) cultures significantly increased the mRNA levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), and remarkably elevated the protein levels of these two neurotrophic factors. Our data provide the first evidence that pitx3 expressing cells are able to upregulate the expression of BDNF and GDNF. Therefore, Pitx3 might be a good target for the treatment of Parkinson's disease. PMID- 17350005 TI - Putting the clamps on membrane fusion: how complexin sets the stage for calcium mediated exocytosis. AB - Three recent papers have addressed a long-standing question in exocytosis: how does a sudden calcium influx trigger a coordinated synchronous release in regulated exocytosis [Giraudo, C.G., Eng, W.S., Melia, T.J. and Rothman, J.E. (2006) A clamping mechanism involved in SNARE-dependent exocytosis. Science 313, 676-680; Schaub, J.R., Lu, X., Doneske, B., Shin, Y.K. and McNew, J.A. (2006) Hemifusion arrest by complexin is relieved by Ca(2+)-synaptotagmin I. Nat. Struct. Mol. Biol. 13, 748-750; Tang, J., Maximov, A., Shin, O.H., Dai, H., Rizo, J. and Sudhof, T.C. (2006) A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell 126, 1175-1187]? Using diverse approaches that include cell-free reconstitution of the membrane fusion machinery and in vivo manipulation of fusogenic proteins, these groups have established that the complexin proteins are fusion clamps. By arresting vesicle secretion just prior to fusion, complexin primes select vesicles for a fast, synchronous response to calcium. PMID- 17350006 TI - Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells. AB - Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells. PMID- 17350007 TI - Survival rate of human oocytes and pregnancy outcome after vitrification using slush nitrogen in assisted reproductive technologies. AB - OBJECTIVE: To report the survival rate of oocytes and the rate of successful pregnancies obtained from super-rapid cooling of oocytes using slush nitrogen (SN(2)). DESIGN: Prospective clinical research. SETTING: A university-affiliated hospital. PATIENT(S): Twenty-eight infertile women who underwent 30 cycles of IVF ET using previously vitrified oocytes. INTERVENTION(S): Oocytes were vitrified by super-rapid cooling using SN(2). MAIN OUTCOME MEASURE(S): Morphological normality of thawed oocytes and clinical outcome. RESULT(S): In 30 cycles of ovarian stimulation for IVF, 364 surplus oocytes from 28 patients were vitrified using SN(2). Three hundred two (85.1% +/- 2.9%) of the oocytes survived after warming. Fertilization and cleavage rates were 77.4% +/- 3.5% (168/218) and 94.3% +/- 2.1% (158/168), respectively. Thirteen pregnancies (43.3%) resulted from 30 uterine transfers of 120 embryos with an implantation rate of 14.2% (17/120). There were no differences between the pregnancy rate after vitrification/warming and that obtained from routine noncryopreserved oocytes. CONCLUSION(S): The present report suggests that super-rapid cooling may improve the clinical efficacy of human oocyte vitrification and may be a valuable tool for human assisted reproductive technologies. PMID- 17350008 TI - Diagnostic accuracy of EUS for vascular invasion in pancreatic and periampullary cancers: a meta-analysis and systematic review. AB - BACKGROUND: Vascular invasion (VI) in a patient with pancreatic or periampullary cancers precludes surgery and indicates a poor prognosis. Published data on the accuracy of EUS in diagnosing VI is varied. OBJECTIVE: The aim of this meta analysis was to evaluate the accuracy of EUS in diagnosing VI in patients with pancreatic and periampullary cancers. DESIGN: Data from EUS studies were pooled according to the Mantel-Haenszel and DerSimonian Laird methods. PATIENTS: EUS studies in which VI was confirmed by surgery or angiography were selected. INTERVENTIONS: EUS. MAIN OUTCOME MEASURES: Pooled estimates of sensitivity, specificity, likelihood ratios, and diagnostic odds ratio of EUS. RESULTS: Data were extracted from 29 studies (N = 1308) that met the inclusion criteria. The pooled sensitivity of EUS in diagnosing VI was 73% (95% CI, 68.8-76.9) and the pooled specificity was 90.2% (95% CI, 87.9-92.2). The positive likelihood ratio for diagnosing VI by EUS was 9.1 (95% CI, 4.6-17.9) and the negative likelihood ratio was 0.3 (95% CI, 0.2-0.5). Diagnostic odds ratio, the odds of having VI in positive as compared with negative EUS studies, was 40.1 (95% CI, 16.1-99.9). The P value for chi(2) heterogeneity for all the pooled estimates was >.05. CONCLUSIONS: Although EUS is the best noninvasive test to diagnose VI in pancreatic and periampullary cancers, this meta-analysis showed that the specificity (90%) is high but the sensitivity (73%) is not as high as suggested. Further refinements in EUS technologies and interpretation may improve the sensitivity for detecting VI. PMID- 17350009 TI - Endoluminal suturing may overcome the limitations of clip closure of a gaping wide colon perforation (with videos). AB - BACKGROUND: It is unclear whether large gaping perforations of the colon can be closed by the endoluminal route. OBJECTIVE: To evaluate the feasibility and the outcome of closure of large perforations of colon with clips and sutures by using through-the-endoscope novel devices. DESIGN: Prospective animal study. SETTING: University hospital. PATIENTS: Ten pigs. INTERVENTIONS: Closure of a 4-cm full thickness colon perforation freshly created by an insulated-tip knife with the InScope Multi-Clip Applier (n = 6) and with the tissue approximation device (n = 4). MAIN OUTCOME MEASUREMENTS: (a) Technical feasibility of closure, (b) clinical monitoring for 2 weeks, (c) necropsy (day 14), (d) healing by a dye-leak test and histology. RESULTS: Endoluminal closure of a 4-cm-long colon perforation was successful in 9 of 10 animals. The clips failed to close a gaping wide colon perforation in 1 animal. The sutures were successful in the closure of both nongaping and gaping perforations. Successful closure resulted in a leakproof sealing at 2 weeks and prevented clinical peritonitis in all the animals in the clip-closure group and in 3 of 4 animals in the suture-closure group. Necropsy at 2 weeks revealed mild peritonitis in 2 of the 5 animals in the clip closure group and in 2 of the 4 animals in the suture-closure group; none developed fecal peritonitis. LIMITATIONS: None. CONCLUSIONS: Endoluminal closure of a 4-cm colon perforation with clips was successful in the majority of cases. Sutures were useful in the closure of gaping colon perforations that could not be closed with clips. PMID- 17350010 TI - ACTH stimulation in four Asian bull elephants (Elephas maximus): an investigation of androgen sources in bull elephants. AB - The phenomenon of musth is a very stressful event, both behaviorally and physiologically. An ACTH stimulation test was conducted in four adult Asian bull elephants to investigate the possibility that the classical hypothalamic pituitary-adrenal (HPA) axis is active during musth, resulting in an increase in adrenally produced steroids. Serum cortisol, testosterone (T), androstenedione (A4), androstenediol (A5), and dehydroepiandrosterone (DHEA) were measured. Cortisol increased 3-10 times above baseline in response to ACTH stimulation, and DHEA doubled. A4 and A5 were erratic, while testosterone decreased significantly in all bulls. The pattern of results suggests that the adrenal steroid increase which occurs during musth results from some mechanism other than the classical HPA axis. PMID- 17350011 TI - Effect of melatonin on salt gland and kidney function of gulls, Larus glaucescens. AB - This study examined effects of exogenous melatonin on osmoregulatory hormones and water and sodium secretion by salt glands and excretion via the kidneys of Glaucous-winged gulls (Larus glaucescens). Six saline acclimated gulls were injected with inulin and paraminohippuric acid and then infused with 500 mM NaCl to stimulate salt gland secretion. Each bird was given infusions of NaCl alone and NaCl plus melatonin. Experiments were made one week apart in a randomized order. A large blood sample (to measure osmoregulatory hormones) was taken before infusion, at secretion, and at the end of infusion. A small blood sample was taken at the midpoint of each of six 10 min sequential collections of salt gland secretion and urine. Melatonin tended to increase plasma sodium concentration, did decrease plasma osmolality, but did not affect potassium concentration. Melatonin did not affect salt gland secretion rate or concentration nor renal plasma flow or glomerular filtration. Melatonin increased urine flow rate, tended to increase urine sodium concentration, and did decrease urine potassium concentration. Combined renal and extrarenal sodium excretion was greater during MT treatment. During NaCl infusion, angiotensin II increased, aldosterone decreased, and arginine vasotocin remained unchanged. Melatonin did not affect these responses. These data suggest an osmoregulatory role for melatonin in birds with salt glands. PMID- 17350012 TI - A longitudinal study of LH, gonadal and adrenal steroids in four intact Asian bull elephants (Elephas maximus) and one castrate African bull (Loxodonta africana) during musth and non-musth periods. AB - During their annual musth cycle, adult African and Asian bull elephants have increased gonadal androgens (testosterone [T], dihydrotestosterone [DHT], androstenedione [A4]). Because musth is a physiologically and psychologically stressful time, this study was conducted to investigate whether the adrenal glands (stimulated by stress) increase production of both glucocorticoids and androgens during musth. Weekly serum samples were taken for 11-15 months from four intact adult Asian bull elephants, and from a castrate African bull elephant who exhibits musth. Testosterone, androstenediol (A5), A4, luteinizing hormone (LH), cortisol, and dehydroepiandrosterone (DHEA) were measured in each sample. In three of the four intact bulls, all hormones measured increased during musth. Adrenal androgens were strongly correlated with LH and testicular androgens, though not to cortisol. None of the hormones measured in the castrate bull increased during his musth cycles. While the significance of adrenal activity in the elephant during musth has yet to be determined, this study provides evidence that the adrenal gland actively produces both glucocorticoids and androgens during musth in the Asian elephant. PMID- 17350013 TI - Amino acids are more important insulinotropins than glucose in a teleost fish, barfin flounder (Verasper moseri). AB - The insulinotropic effects of eighteen L-amino acids, two D-amino acids, and glucose were investigated to evaluate the priority of those as stimulators of insulin secretion in barfin flounder (Verasper moseri). This is also the first step in characterizing the insulinotropin-sensing molecule. After intramuscular injection of amino acids or glucose at doses of 3.50 and 1.75 mmol/kg body weight, plasma was collected periodically to determine plasma insulin level. Twelve amino acids and glucose showed insulinotropic effects. Four L-amino acids (Arg, Ala, Met, Ser) produced significantly higher integrated levels of plasma insulin (12.4-34.8 ng/ml) than glucose (average: 4.7 ng/ml) during 3h after injection. D-Amino acids (Arg, Ala) showed no activity. This indicates that many amino acids have strong insulinotropic activities and supports a classic idea, which is well known but has not been confirmed, that amino acids rather than glucose are the important insulinotropins in fish. This study also indicates that the insulinotropic activity of amino acids is restricted to L-amino acids and establishes which amino acids are the strongest stimulators of the insulinotropin sensor in barfin flounder. Co-injection of insulin and L-Thr, L-Ala, or glucose produced a hypoglycemic and hypoaminoacidemic state, indicating that insulin can lower blood amino acid level as well as blood sugar level. This study suggests that insulin plays a more important role than glucose in the regulation of blood L-amino acid metabolism, at least in flounder. PMID- 17350015 TI - Stabilizing frequency weighted controller reduction approach. AB - This note addresses the problem of instability in frequency weighted controller reduction methods based on similarity transformations. The aim is to reduce the complexity of the controllers derived by modern controller design packages for practical applications. For a given controller a framework is proposed that parameterizes a set of reduced controllers that preserve the stability of the closed loop system. Then based on this result a complementary algorithm to obtain a stabilizing stable reduced controller based on the two sided frequency weighted reduction method is presented. In addition, a sufficient condition for the existence of such a framework is derived. PMID- 17350014 TI - GnRH and GnRH receptors in metazoa: a historical, comparative, and evolutive perspective. AB - About 50years after Harris's first demonstration of its existence, GnRH has strongly stimulated the interest and imagination of scientists, resulting in a high number of studies in an increasing number of species. For the endocrinologist, GnRH, via its actions on the synthesis and release of pituitary gonadotrophins, is first an essential hormone for the initiation and maintenance of the reproductive axis, but recent data suggest that GnRH emerged in animals lacking a pituitary. In this context, this review intends to explore the current status of knowledge on GnRH and GnRH receptors in metazoa in order to see if it is possible to draw an evolutive scenario according to which GnRH actions progressively evolved from the control of simple basic functions in early metazoa to an indirect mean of controlling gonadal activity in vertebrates through a sophisticated network of finely tuned neurons developing in a rather fascinating way. This review also intends to provide an evolutive scenario based on the recent advances of whole genome sequencing possibly explaining the number of GnRH and GnRH receptor variants according to the 2R and 3R theories accompanied by gene losses. PMID- 17350016 TI - Constrained H2 approximation of multiple input-output delay systems using genetic algorithm. AB - The paper presents a constrained H2 approximation method for multiple input output delay systems by using a genetic algorithm. The H2 error between the original and the approximate models is minimized subject to constraints on the H(infinity) error between them and the matching of their steady-state under step inputs. In particular, the H2 error is used as the objective (fitness) function for minimization with the best parameters of the approximate model obtained by repeating the genetic operations on the population incorporated a parameter search space expansion scheme. The effectiveness of the proposed method is demonstrated by numerical examples. It is shown that the approximate models obtained by this approach have better approximation performance in both the H2 and H(infinity) norms, as well as the steady-state response, than those obtained by a previous gradient-based minimization approach. PMID- 17350017 TI - By the day nurses bank up in a casual pool! PMID- 17350018 TI - Linking demography and host dispersal to Trichuris arvicolae distribution in a cyclic vole species. AB - Spatial structure in the distribution of pathogen infection can influence both epidemiology and host-parasite coevolutionary processes. It may result from the spatial heterogeneity of intrinsic and extrinsic factors, or from the local population dynamics of hosts and parasites. In this study, we investigated the effects of landscape, host dispersal and demography (population abundance and phase of the fluctuation) on the distribution of a gastro-intestinal nematode Trichuris arvicolae in the fossorial water vole Arvicola terrestris sherman. This rodent exhibits outbreaks occurring regularly in Franche-Comte (France). Thirteen out-of-phase populations were studied in autumn 2003. They exhibited highly different T. arvicolae prevalences. The heterogeneity in prevalences was not explained by population structure, landscape or vole abundance, but by the phase of the vole population fluctuations. Populations at the end of the high density phase showed null prevalence whereas populations in increase or outbreak phases exhibited higher prevalences. Population genetic analyses based on microsatellites revealed significant differentiation between vole populations, and higher dispersal rates of young voles compared with old ones. These younger individuals were also infected more frequently than older voles. This suggested a role of host dispersal in the distribution of T. arvicolae. However, there was a strong discrepancy between the spatial patterns of prevalence and of host genetics or demographic phase. Genetic differentiation and differences in demographic phase exhibited significant spatial autocorrelations whereas prevalence did not. We concluded that the distribution of T. arvicolae is influenced by vole dispersal, although this effect might be overwhelmed by local adaptation processes or environmental conditions. PMID- 17350019 TI - Regulatory CD4+ CD25+ Foxp3+ T cells expand during experimental Plasmodium infection but do not prevent cerebral malaria. AB - Pathogenic CD8+ T cells are implicated in the physiopathological mechanisms leading to experimental cerebral malaria (CM) in Plasmodium berghei ANKA (PbA) infected mice. Therefore, we hypothesised that in CM susceptible mice the neuropathology could be, at least in part, the result of an inefficient control of pathogenic effector T cells by CD4+ CD25+ Treg cells. Remarkably, the number of CD4+ CD25high T cells expressing Foxp3 increased in the spleen during the course of infection. These cells displayed an activated phenotype and consistent with that, CD4+ CD25high Treg cells isolated from PbA-infected mice showed an enhanced regulatory activity in vitro. Surprisingly, these cells do not migrate to the brain at the time of neurological symptoms as the conventional CD4+ T cells do. CM was not exacerbated in anti-CD25 treated mice when infected with PbA one month after treatment, even if splenic CD8+ T cells expressing CD69 increased in these mice. Taken together, these results show that P. berghei infection leads to an increase of the number of splenic CD4+ CD25high Treg cells exhibiting in vitro suppressive function, but they do not seem to be involved in vivo in the protection against CM. PMID- 17350020 TI - Increased risk of incident stroke associated with the cyclooxygenase 2 (COX-2) G 765C polymorphism in African-Americans: the Atherosclerosis Risk in Communities Study. AB - BACKGROUND: A hallmark feature of atherosclerosis is inflammation mediated by prostaglandins (PGs) catalyzed by the enzyme cyclooxygenase (COX). The present study explored whether the COX-2 G-765C polymorphism contributes to increased incidence of coronary heart disease (CHD) or stroke in the large prospective Atherosclerosis Risk in Communities (ARIC) Study. METHODS: Incidences of CHD and stroke were identified through annual follow-up and hospital and death certificate surveillance. The study included 1488 incident CHD and 527 stroke events after an average of 14 years of follow-up. The frequency of the -765C variant allele was markedly different between African-Americans and whites, therefore all analyses were performed separately by race. Due to the small number of persons with the -765CC genotype, heterozygous and homozygous variant genotypes were combined for this analysis. RESULTS: The COX-2 G-765C polymorphism was not a significant predictor of CHD in either racial group, but it was a significant predictor of incident stroke in African-Americans. After adjustment for age and gender, the hazard rate ratio for developing stroke for the CG+CC genotypes relative to the GG genotype was 1.34 (95% confidence interval [CI] 1.03 1.74, P=0.03) in African-Americans. This result was essentially unchanged when established predictors such as smoking, diabetes and hypertension were added to the model (HRR 1.34, 95%CI 1.03-1.76, P=0.03). CONCLUSION: We have found the COX 2 G-765C polymorphism to be a risk factor for incident stroke in African Americans. This study provides additional evidence for utilizing inflammation related genetic polymorphisms for identifying individuals at increased risk for stroke. PMID- 17350021 TI - C-reactive protein genetics is associated with carotid artery compliance in men in The Cardiovascular Risk in Young Finns Study. AB - Although C-reactive protein (CRP) is known to predict cardiovascular events, its status as a causal risk factor is still controversial. CRP gene single nucleotide polymorphisms (SNPs) have been shown to associate with CRP concentration, but no direct independent effect on early atherosclerotic changes has been demonstrated. We aimed to determine if CRP gene polymorphisms or haplotypes are associated with CRP concentration or carotid artery compliance (CAC), an indicator of subclinical atherosclerosis. We genotyped CRP gene polymorphisms -717A>G, -286C>T>A, +1059G>C, +1444C>T and +1846G>A and measured CRP concentration and CAC in 2283 young adults participating in The Cardiovascular Risk in Young Finns Study. A strong association was found between CRP genotypes and CRP concentration, which was also seen at the haplotype level. Linear regression analysis showed an independent effect of each SNP on CRP concentration after adjustment for risk factors, except for +1444 in males. Moreover, -286C>T>A, +1444C>T and +1846G>A were associated with CAC in males, but not in females. Men carrying the SNP -286 allele C had increased CAC after adjusting for risk factors. These data suggest that the presence of high producer CRP genotype is deleterious to carotid elasticity in men. PMID- 17350022 TI - Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages. AB - Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10 50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions. PMID- 17350023 TI - Correlation of carotid atheromatous plaque inflammation with biomechanical stress: utility of USPIO enhanced MR imaging and finite element analysis. AB - OBJECTIVE: The aim of this study was to explore whether there is a relationship between the degree of MR-defined inflammation using ultra small super paramagnetic iron oxide (USPIO) particles, and biomechanical stress using finite element analysis (FEA) techniques, in carotid atheromatous plaques. METHODS AND RESULTS: 18 patients with angiographically proven carotid stenoses underwent multi-sequence MR imaging before and 36 h after USPIO infusion. T(2)(*) weighted images were manually segmented into quadrants and the signal change in each quadrant normalised to adjacent muscle was calculated after USPIO administration. Plaque geometry was obtained from the rest of the multi-sequence dataset and used within a FEA model to predict maximal stress concentration within each slice. Subsequently, a new statistical model was developed to explicitly investigate the form of the relationship between biomechanical stress and signal change. The Spearman's rank correlation coefficient for USPIO enhanced signal change and maximal biomechanical stress was -0.60 (p=0.009). CONCLUSIONS: There is an association between biomechanical stress and USPIO enhanced MR-defined inflammation within carotid atheroma, both known risk factors for plaque vulnerability. This underlines the complex interaction between physiological processes and biomechanical mechanisms in the development of carotid atheroma. However, this is preliminary data that will need validation in a larger cohort of patients. PMID- 17350024 TI - Replacement of dietary soy protein isolate with concentrates of soy 7S or 11S globulin has minimal or no effects on plasma lipoprotein profiles and biomarkers of coronary risk in monkeys. AB - Effects of soy peptide fractions on risk factors for coronary heart disease are unknown. We compared the effects of a soy protein isolate, a soy 7S fraction concentrate and a soy 11S fraction concentrate on total plasma cholesterol, HDL cholesterol, LDL+VLDL cholesterol and triacylglycerol in adult male cynomolgus monkeys. Effects on biomarkers of coronary risk [soluble E-selectin, vascular cell-adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta-1 (TGF-beta-1) and plasminogen activator inhibitor-1 (PAI-1)] were also determined. Relative to a soy- and isoflavone-free diet (casein and lactalbumin as the source of protein), soy protein isolate had the predicted favorable effects on plasma lipoproteins, i.e., reductions in total and VLDL+LDL cholesterol (8 and 14%, respectively) (P's<0.05) and a 41% increase in HDL (P<0.05). Effects of 7S and 11S on these variables were less favorable. In fact, there was a 7% increase in total plasma cholesterol concentration (P<0.05) in monkeys fed 7S that was accounted for primarily by an increase in VLDL+LDL cholesterol. There was no effect of any protein source on cardiovascular biomarkers. Replacement of dietary soy protein isolate with concentrated 7S or 11S does not result in improvement of plasma lipoprotein profiles or cardiovascular biomarkers in monkeys. PMID- 17350025 TI - Epidermal growth factor stimulates Rac1 and p21-activated kinase in vascular smooth muscle cells. AB - Epidermal growth factor (EGF) has been shown to be a potent mitogen for vascular smooth muscle cells (VSMC) both in vitro and in vivo, thus contributing to the development of atherosclerosis and hypertension. Stimulation of Rho-family GTPases Rac/Cdc42 exerts pleiotropic cellular effects and have been demonstrated to contribute to EGF-induced proliferation in other cell systems. However, the effect of EGF on Rac/Cdc42 activation is unknown for VSMC. In the present report, we evaluated stimulation of Rac/Cdc42 by EGF in VSMC performing PAK-PBD binding assay. EGF treatment of VSMC induced time and concentration dependent binding of GTP-bound Rac1 to PAK-PBD peaking at 1 min and showing sustained activation up to 15 min. However, stimulation of Cdc42 could not be demonstrated. To further evaluate downstream effectors of Rac1 stimulation of p21-activated kinase (PAK) and c-Jun N-terminal kinase (JNK) by EGF was determined. In VSMC, EGF sequentially stimulated PAK, peaking at 5 min, and JNK, peaking at 15 min. Pretreatment of VSMC by EGF receptor specific tyrosine kinase inhibitor AG1478 and non-specific tyrosine kinase inhibitor genistein inhibited EGF-induced activation of Rac1, PAK and JNK, whereas tyrosine kinase inhibitors specific for Src (PP1) and specific for platelet-derived growth factor (AG1296) had no effect. Specific inhibition or Rac1 by NSC23766 attenuated EGF-induced [(3)H] thymidine incorporation in VSMC. Our data provide evidence for EGF-induced Rac1 activation and implicate PAK and JNK as downstream targets of Rac1 in EGF signal transduction in VSMC. PMID- 17350026 TI - Coronary calcification is more predictive of carotid intimal medial thickness in black compared to white middle aged men. AB - BACKGROUND: Race-specific data for the association between coronary artery calcification (CAC) and carotid intimal medial thickness (IMT) are limited. We sought to compare black-white specific associations of these two measures. METHODS: We conducted a population-based study of 379 randomly selected men aged 40-49 years (84 black and 295 white) from Allegheny County, US (2004-2006). Agatston CAC score was evaluated by electron-beam tomography and carotid IMT was evaluated by ultrasonography. RESULTS: Compared to white men, black men had similar prevalence of CAC (p=0.56) and higher total carotid IMT (p<0.001). In black and white men, CAC score had significant positive correlations with total carotid IMT (r=0.47 and r=0.24, respectively, p<0.001 for both) as well as the IMT for the common carotid artery (CCA), internal carotid artery and carotid bulb. The associations of CAC with total and CCA IMT were significantly stronger in black (beta=0.07 and beta=0.05, respectively) than white men (beta=0.03 and beta=0.01, respectively) after adjustment for traditional coronary risk factors (p=0.046 and p=0.036, respectively). CONCLUSIONS: In black and white middle aged men, CAC score had significant positive correlations with total and segmental carotid IMT. CAC was more predictive of total and CCA IMT in black than white men independent of coronary risk factors. PMID- 17350027 TI - Numerical simulation of saccular aneurysm hemodynamics: influence of morphology on rupture risk. AB - The governing equations for pulsatile fluid flow were solved in their finite volume formulation in order to simulate blood flow in a variety of three dimensional aneurysm geometries. The influence of geometric factors on flow patterns and fluid mechanical forces was studied with the goal of identifying the risk of aneurysm rupture. Aneurysm morphology was characterized by quantitative shape indices reflecting the three dimensionality of the vasculature derived from clinical studies. Recirculation zones and secondary flows were observed in aneurysms and arteries. Regions of extreme and alternating shear stress were observed and identified as sites for potential aneurysm rupture. The ellipticity of an aneurysm was observed to be strongly correlated with wall shear stress at the aneurysm fundus, while its non-sphericity, volume, and degree of undulation were more weakly correlated. PMID- 17350028 TI - Use and misuse of supervised pattern recognition methods for interpreting compositional data. AB - In this paper, the critical aspects of supervised learning pattern recognition techniques are examined in order to apply the suitable methodology avoiding its abuse and misuse that could provide pitfalls and misleading results. PMID- 17350029 TI - Synthesis, isolation, and redispersion of resorcinarene-capped anatase TiO2 nanoparticles in nonaqueous solvents. AB - C-undodecylcalix[4]-resorcinarene (C(11)-resorcinarene)-capped anatase TiO(2) nanoparticles have been synthesized and could be isolated and redispersed in different nonaqueous solvents. The adsorption of C(11)-resorcinarene onto the surface of TiO(2) nanoparticles led the shifting of the onset wavelength of the optical absorption in the visible range along with a broad band centered at 422 nm corresponding to ligand-to-metal charge transfer transition within the surface titanium(IV)-C(11)-resorcinarene complex. The interaction of TiO(2) nanoparticle with C(11)-resorcinarenes was investigated by photoluminescence (PL). Proton nuclear magnetic resonance ((1)H NMR) spectroscopy study revealed that the C(11) resorcenarene molecules adsorbed chemically onto the surfaces of TiO(2) nanoparticles. The average particle diameter of bare anatase TiO(2) and C(11) resorcinarene-capped TiO(2) was determined using transmission electron microscopy (TEM) and was found to be equal to ca. 5 nm. PMID- 17350030 TI - Synthesis and stabilization of Prussian blue nanoparticles and application for sensors. AB - Prussian blue (PB) nanoparticles were synthesized by two methods from FeCl2 and K3Fe(CN)6 and from FeCl3 and K3Fe(CN)6 based on the method published by Fiorito et al., and stabilized by different polymers like polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polyallylamine hydrochloride (PAH), polydiallyl dimethyldiammonium chloride (PDDA) and polystyrene sulfonate (PSS). The effect of the monomer/Fe3+ ratio was studied regarding the average particle size and zeta potential. The forming PB structure was checked by X-ray diffraction. The stabilization was successful for every applied polymer, but the average particle size significantly differs. Particle size distributions were determined by Malvern type nanosizer equipment and by transmission electron microscope (TEM) and zeta potential values were determined for the obtained stabile samples. The results revealed that by using FeCl2 and K3Fe(CN)6 for PB preparation particles with narrow size distribution and average diameter of 1.7 nm occurred but stabilization was necessary. By the other method the dispersion was stabile with 182 nm particles but the particle size exponentially decreased to 18 nm with increasing PVP concentration. Ultrathin nanofilms were prepared on glass support by the alternating layer-by-layer (LbL) method from PB particles and PAH. The morphology of the prepared films was investigated also by AFM. The films were immobilized on interdigitated microsensor electrodes (IME) and tested in sensing hydrogen peroxide and different acids like acetic acid, hydrochloric acid vapors. PMID- 17350031 TI - Adsorption of toxic organic compounds from water with hydrophobic silica aerogels. AB - Silica monolith aerogels with different degrees of hydrophobicity were prepared by incorporating methyltrimethoxysilane (MTMS) or trimethylethoxysilane (TMES) in standard sol-gel synthesis followed by supercritical drying of gels with carbon dioxide (CO(2)) at 40 degrees C and 100 bar. The hydrophobicity of the aerogels was tested by measuring the contact angle (theta). The aerogels were also characterised by FTIR, DSC, and porosity measurements. Adsorption capacity measurements show that such modified hydrophobic silica aerogels are excellent adsorbents for different toxic organic compounds from water. In comparison to granulated active carbon (GAC) they exhibit capacities which are from 15 to 400 times higher for all tested compounds. Adsorption properties of hydrophobic silica aerogel remain stable even after 20 adsorption/desorption cycles. PMID- 17350032 TI - An amperometric immunosensor for separation-free immunoassay of CA125 based on its covalent immobilization coupled with thionine on carbon nanofiber. AB - A carbon nanomaterial, soluble carbon nanofiber, was used for the first time to construct an immunosensor for a rapid separation-free immunoassay. The acidic oxidation of the carbon nanofiber provided its solubility and wettability for convenient preparation of a porous carbon nanofiber membrane and a larger number of active sites for covalent binding of carcinoma antigen-125 (CA125) and thionine as electron transfer mediator. This matrix was a suitable environment for the immobilized protein. The immobilized HRP-labeled immunoconjugate showed good enzymatic activity for the oxidation of thionine by hydrogen peroxide. With a competitive mechanism, the differential pulse voltammetric peak current of this system decreased linearly with increasing CA125 concentration (from 2 to 75 U/ml) in the incubation solution. The CA125 immunosensor showed good precision, high sensitivity, acceptable stability and reproducibility with a detection limit of 1.8 U/ml. The soluble carbon nanofiber is a novel method for preparation of immunosensors. PMID- 17350033 TI - Ex vivo delivered stromal cell-derived factor-1alpha promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. AB - We aimed to optimize non-viral transfection of human stromal cell derived factor (SDF-1alpha) gene into skeletal myoblasts (SkM) and, transplant these cells to establish transient SDF-1alpha gradient to favor extra-cardiac stem cell translocation into infarcted heart. Optimized conditions for transfection of SDF 1alpha gene into syngenic SkM were achieved using FuGene6/phSDF-1alpha (3:2v/w, 4 h transfection) with 125 microM ZnCl(2) (p<0.001). After characterization for transgene overexpression by immunostaining, ELISA and PCR, the cells were transplanted in female rat model of myocardial infarction. Thirty-six rats were grouped (n=12/group) to receive 70 microl DMEM without cells (group-1) or containing 1.5 x 10(6) non-transfected (group-2) or SDF-1alpha transfected SkM (group-3). On day 4 post-transplantation (in 4 animals/group), marked expression of SDF-1alpha/sry-gene (p=0.003), total Akt, phospho-Akt and Bcl2 was observed in group-3. The number of CD31(+), C-kit(+) and CD34(+) cells was highest in group-3 hearts (p<0.01). Blood vessel density in group-3 was higher in both scar and peri scar regions (p<0.001) as compared with other groups. Echocardiography showed improved indices of left ventricle contractile function and remodeling in group-3 (p<0.05) as compared with groups-1 and -2. We conclude that ex vivo SDF-1alpha transgene delivery promotes stem and progenitor cell migration to the heart, activates cell survival signaling and enhances angiomyogenesis in the infarcted heart. PMID- 17350034 TI - The use of human cardiac tissue in biophysical research: the risks of translation. AB - There has been increasing enthusiasm for biomedical research that focuses directly on human pathophysiology, in part fueled by the recent NIH roadmap initiative. While this approach has considerable merit, a myopic and primary focus on human disease and on human tissue introduces a plethora of research risks and concerns that could potentially complicate data interpretation and retard scientific progress. While some of these issues are generic when one extrapolates from animal models to the human circumstance, others are more specific to the cardiovascular system in general and to the study of cardiocyte biology in particular. This brief review will highlight some of these. PMID- 17350036 TI - Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice. AB - Elevated activities of the sympathetic nerve and renin-angiotensin systems are common features of heart failure. This study was designed to investigate the roles of the AT1 receptor in cardiac hypertrophy and oxidative stress during excessive beta-adrenoceptor stimulation using an AT1 receptor antagonist (ARB) and AT1a receptor-deficient (AT1aR(-/-)) mice. Isoproterenol (ISO) was given to C57BL mice with or without ARB (olmesartan) treatment and to AT1aR(-/-) mice by a subcutaneously implanted osmotic mini-pump for 11 days at a rate of 15 mg/kg/day. Chronic ISO infusion to C57BL mice caused concentric cardiac hypertrophy (sham; 4.1+/-0.1, ISO; 5.2+/-0.2 mg/g heart to body weight ratio), accompanied by enhancement of cardiac collagen accumulation, lipid peroxidation, superoxide generation and NADPH oxidase activity. The AT1a and beta-1,2 receptor mRNA expressions were down-regulated in the heart of ISO-infused mice. Olmesartan markedly suppressed cardiac mass enlargement as well as increases of oxidative indicators without any effects on heart rate. Olmesartan did not affect the cardiac angiotensin and beta-adrenergic receptor mRNA expression patterns. The AT1a receptor contribution to ISO-induced cardiac hypertrophy was reproduced in AT1aR(-/-) mice. These data suggest that the AT1 receptor plays a crucial role in the development of cardiac hypertrophy and oxidative stress under excessive beta adrenergic stimulation, and that ARB treatment is beneficial for sympatho excitatory cardiac hypertrophy and failure in mice. PMID- 17350035 TI - Cardioprotection and mitochondrial S-nitrosation: effects of S-nitroso-2 mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia-reperfusion injury. AB - Mitochondrial dysfunction is a key pathologic event in cardiac ischemia reperfusion (IR) injury, and protection of mitochondrial function is a potential mechanism underlying ischemic preconditioning (IPC). Acknowledging the role of nitric oxide (NO()) in IPC, it was hypothesized that mitochondrial protein S nitrosation may be a cardioprotective mechanism. The reagent S-nitroso-2 mercaptopropionyl-glycine (SNO-MPG) was therefore developed to enhance mitochondrial S-nitrosation and elicit cardioprotection. Within cardiomyocytes, mitochondrial proteins were effectively S-nitrosated by SNO-MPG. Consistent with the recent discovery of mitochondrial complex I as an S-nitrosation target, SNO MPG inhibited complex I activity and cardiomyocyte respiration. The latter effect was insensitive to the NO() scavenger c-PTIO, indicating no role for NO() mediated complex IV inhibition. A cardioprotective role for reversible complex I inhibition has been proposed, and consistent with this SNO-MPG protected cardiomyocytes from simulated IR injury. Further supporting a cardioprotective role for endogenous mitochondrial S-nitrosothiols, patterns of protein S nitrosation were similar in mitochondria isolated from Langendorff perfused hearts subjected to IPC, and mitochondria or cells treated with SNO-MPG. The functional recovery of perfused hearts from IR injury was also improved under conditions which stabilized endogenous S-nitrosothiols (i.e. dark), or by pre ischemic administration of SNO-MPG. Mitochondria isolated from SNO-MPG-treated hearts at the end of ischemia exhibited improved Ca(2+) handling and lower ROS generation. Overall these data suggest that mitochondrial S-nitrosation and complex I inhibition constitute a protective signaling pathway that is amenable to pharmacologic augmentation. PMID- 17350037 TI - Structural Insight into concerted inhibition of alpha 2 beta 2-type aspartate kinase from Corynebacterium glutamicum. AB - Aspartate kinase (AK) catalyzes the first step of the biosynthesis of the aspartic acid family amino acids, and is regulated via feedback inhibition by end products including Thr and Lys. To elucidate the mechanism of this inhibition, we determined the crystal structure of the regulatory subunit of AK from Corynebacterium glutamicum at 1.58 A resolution in the Thr-binding form, the first crystal structure of the regulatory subunit of alpha(2)beta(2)-type AK. The regulatory subunit contains two ACT domain motifs per monomer and is arranged as a dimer. Two non-equivalent ACT domains from different chains form an effector binding unit that binds a single Thr molecule, and the resulting two effector binding units of the dimer associate perpendicularly in a face-to-face manner. The regulatory subunit is a monomer in the absence of Thr but becomes a dimer by adding Thr. The dimerization is eliminated in mutant AKs with changes in the Thr binding region, suggesting that the dimerization induced by Thr binding is a key step in the inhibitory mechanism of AK from C. glutamicum. A putative Lys-binding site and the inhibitory mechanism of CgAK are discussed. PMID- 17350038 TI - Solution structure and self-association properties of the p8 TFIIH subunit responsible for trichothiodystrophy. AB - Trichothiodystrophy (TTD) is a rare hereditary multi-system disorder associated with defects in nucleotide excision repair (NER) and transcription as consequences of mutations in XPB, XPD and p8/TTD-A subunits of transcription factor IIH (TFIIH). Here, we report the solution structure of the p8/TTD-A protein, a small alpha/beta protein built around an antiparallel beta-sheet that forms a homodimer with an extended interface. In order to characterize the dimer interface, we have introduced a mutation at position 44, which destabilizes the dimeric form of the protein. We have shown that this mutation has no effect on the intrinsic ability of p8/TTD-A to stimulate NER in vitro, but affects the capacity of p8/TTD-A to restore TFIIH concentration in TTD-A fibroblasts. Point mutations found in TTD-A patients are discussed on the basis of the present structure. PMID- 17350039 TI - The structure of the KinA-Sda complex suggests an allosteric mechanism of histidine kinase inhibition. AB - The Bacillus subtilis histidine kinase KinA controls activation of the transcription factor governing sporulation, Spo0A. The decision to sporulate involves KinA phosphorylating itself on a conserved histidine residue, after which the phosphate moiety is relayed via two other proteins to Spo0A. The DNA damage checkpoint inhibitor Sda halts this pathway by binding KinA and blocking the autokinase reaction. We have performed small-angle X-ray scattering and neutron contrast variation studies on the complex formed by KinA and Sda. The data show that two Sda molecules bind to the base of the DHp dimerization domain of the KinA dimer. In this position Sda does not appear to be able to sterically block the catalytic domain from accessing its target histidine, as previously proposed, but rather may effect an allosteric mode of inhibition involving transmission of the inhibitory signal via the four-helix bundle that forms the DHp domain. PMID- 17350040 TI - Kinetic and structural characterisation of Escherichia coli nitroreductase mutants showing improved efficacy for the prodrug substrate CB1954. AB - Escherichia coli nitroreductase (NTR) is a flavoprotein that reduces a variety of quinone and nitroaromatic substrates. Among these substrates is the prodrug 5 [aziridin-1-yl]-2,4-dinitrobenzamide (CB1954) that is activated by NTR to form two products, one of which is highly cytotoxic. NTR in combination with CB1954 has entered clinical trials for virus-directed enzyme-prodrug therapy of cancer. Enhancing the catalytic efficiency of NTR for CB1954 is likely to improve the therapeutic potential of this system. We previously identified a number of mutants at six positions around the active site of NTR that showed enhanced sensitisation to CB1954 in an E. coli cell-killing assay. In this study we have purified improved mutants at each of these positions and determined their steady state kinetic parameters for CB1954 and for the antibiotic nitrofurazone. We have also made a double mutant, combining two of the most beneficial single mutations. All the mutants show enhanced specificity constants for CB1954, and, apart from N71S, the enhancement is selective for CB1954 over nitrofurazone. One mutant, T41L, also shows an increase in selectivity for reducing the 4-nitro group of CB1954 rather than the 2-nitro group. We have determined the three-dimensional structures of selected mutants bound to the substrate analogue nicotinic acid, using X-ray crystallography. The N71S mutation affects interactions of the FMN cofactor, while mutations at T41 and F124 affect the interactions with nicotinic acid. The structure of double mutant N71S/F124K combines the effects of the two individual single mutations, but it gives a greater selective enhancement of activity with CB1954 over nitrofurazone than either of these, and the highest specificity constant for CB1954 of all the mutations studied. PMID- 17350041 TI - The acylaminoacyl peptidase from Aeropyrum pernix K1 thought to be an exopeptidase displays endopeptidase activity. AB - Mammalian acylaminoacyl peptidase, a member of the prolyl oligopeptidase family of serine peptidases, is an exopeptidase, which removes acylated amino acid residues from the N terminus of oligopeptides. We have investigated the kinetics and inhibitor binding of the orthologous acylaminoacyl peptidase from the thermophile Aeropyrum pernix K1 (ApAAP). Complex pH-rate profiles were found with charged substrates, indicating a strong electrostatic effect in the surroundings of the active site. Unexpectedly, we have found that oligopeptides can be hydrolysed beyond the N-terminal peptide bond, demonstrating that ApAAP exhibits endopeptidase activity. It was thought that the enzyme is specific for hydrophobic amino acids, in particular phenylalanine, in accord with the non polar S1 subsite of ApAAP. However, cleavage after an Ala residue contradicted this notion and demonstrated that P1 residues of different nature may bind to the S1 subsite depending on the remaining peptide residues. The crystal structures of the complexes formed between the enzyme and product-like inhibitors identified the oxyanion-binding site unambiguously and demonstrated that the phenylalanine ring of the P1 peptide residue assumes a position different from that established in a previous study, using 4-nitrophenylphosphate. We have found that the substrate-binding site extends beyond the S2 subsite, being capable of binding peptides with a longer N terminus. The S2 subsite displays a non-polar character, which is unique among the enzymes of this family. The S3 site was identified as a hydrophobic region that does not form hydrogen bonds with the inhibitor P3 residue. The enzyme-inhibitor complexes revealed that, upon ligand-binding, the S1 subsite undergoes significant conformational changes, demonstrating the plasticity of the specificity site. PMID- 17350042 TI - Ubiquitin-dependent proteolysis of the microtubule end-binding protein 1, EB1, is controlled by the COP9 signalosome: possible consequences for microtubule filament stability. AB - The COP9 signalosome (CSN) is a regulatory particle of the ubiquitin (Ub) proteasome system (UPS) consisting of eight subunits (CSN1-CSN8). We show that the CSN stabilizes the microtubule end-binding protein 1 (EB1) towards degradation by the UPS. EB1, the master regulator of microtubule plus ends, controls microtubule growth and dynamics. Therefore, regulation of EB1 stability by the CSN has consequences for microtubule function. EB1 binds the CSN via subunit CSN5. The C terminus of EB1 is sufficient for interaction with the CSN. Dimerization of EB1 is a prerequisite for complex association and subsequent CSN mediated phosphorylation, as revealed by studies with the EB1I224A mutant, which is unable to dimerize. In cells, EB1 and CSN co-localize to the centrosome, as demonstrated by confocal fluorescence microscopy. EB1 is ubiquitinated and its proteolysis can be inhibited by MG132, demonstrating that it is a substrate of the UPS. Its degradation is accelerated by inhibition of CSN-associated kinases. HeLa cells permanently expressing siRNAs against CSN1 (siCSN1) or CSN3 (siCSN3) exhibit reduced levels of the CSN complex accompanied by lower steady-state concentrations of EB1. In siCSN1 cells, EB1 is less phosphorylated as compared with control cells, demonstrating that the protein is most likely protected towards the UPS by CSN-mediated phosphorylation. The CSN-dependent EB1 stabilization is not due to the CSN-associated deubiquitinating enzyme USP15. Treatment with nocodazole revealed a significantly increased sensitivity of siCSN1 and siCSN3 cells towards the microtubule depolymerizing drug accompanied by a collapse of microtubule filaments. A nocodazole-induced cell-cycle arrest was partially rescued by CSN1 or EB1. These data demonstrate that the CSN dependent protection of EB1 is important for microtubule function. PMID- 17350043 TI - Cognitive and functional impairment in hypertensive brain microangiopathy. AB - Brain microangiopathy, whose neuroimaging expression is represented by age related white matter changes (ARWMC), is largely due to hypertension and it is, in turn, responsible for geriatric syndromes, including decline in cognitive, functional and motor/gait abilities. This review analyzes the link between hypertension and ARWMC, as well as the complex relationships between ARWMC and cognitive impairment, executive dysfunction, and movement/gait abnormalities. The available evidence supports the hypothesis that these functional consequences of ARWMC are responsible for substantial disability in the elderly. Thus, adequate treatment of hypertension may represent a feasible way to reduce the burden of disability in late life. PMID- 17350044 TI - Relapses matter: the costs & consequences of multiple sclerosis relapses. PMID- 17350045 TI - The emotional and psychological impact of multiple sclerosis relapses. AB - Acute relapses of multiple sclerosis (MS) are experienced as crises that disrupt the status quo for individuals with MS and their families. These unpredictable- and always unexpected--events elicit strong reactions, including grief, anxiety, anger, and guilt, as people struggle to understand why they occur. Although early relapses are a signal for most MS specialists to recommend treatment with one of the approved disease-modifying therapies, the remissions that follow contribute to patient and family denial about the realities of the disease, making it difficult for patients to begin and to adhere to ongoing treatment. Each ensuing attack confronts this denial, forcing patients and families to acknowledge the MS diagnosis and begin adapting to the demands of the illness in their daily lives. This paper discusses the meaning attributed by individuals and families to relapses leading to the MS diagnosis and the recommendation for disease-modifying therapy, the adjustments that are made by patients and their families to residual deficits following acute episodes, and suggestions for clinicians on how they might facilitate the adjustment process. PMID- 17350046 TI - Hyperglycemia independently increases the risk of early death in acute spontaneous intracerebral hemorrhage. AB - BACKGROUND: It is unclear whether hyperglycemia on admission in patients with acute intracerebral hemorrhage (ICH) increases the risk of early death. METHODS: 100 consecutive patients (median age, 67.8 years) with acute supratentorial ICH within 24 h of onset were prospectively enrolled. Clinical characteristics and plasma glucose were assessed in all patients. ICH volume was measured on admission CT (<24 h) and follow-up CT (<48 h) scans. Patients were divided into two groups: the death group, who died within 14 days of onset, and the survival group. The association between early death and clinical characteristics were investigated by multivariate logistic regression analysis. RESULTS: The death group consisted of 11 patients (median age, 77 years), while the survival group consisted of 89 patients (median age, 67 years). The admission plasma glucose level and the ICH volume were higher in the death group than in the survival group (glucose: death, 205 mg/dl vs. survival, 131 mg/dl, p<0.0001; and ICH volume: survival, 13.6+/-15.3 ml vs. death 101.1+/-48.7 ml, p<0.0001). Using receiver operating characteristic (ROC) curve, cut-off values that predicted early death were 150 mg/dl for the glucose level and >20 ml for the initial IVH volume. On multivariate logistic regression analysis, admission plasma glucose level>150 mg/dl (OR 37.5, CI 1.4-992.7, p=0.03) and IVH volume>20 ml (OR 64.6, CI 1.3-3173.5, p=0.04) were independent factors associated with early death. CONCLUSION: Admission hyperglycemia may independently increase the risk of early death in acute spontaneous intracerebral hemorrhage. PMID- 17350047 TI - The psychosocial effect of multiple sclerosis: the impact of relapses. AB - Historically, the disease course of multiple sclerosis (MS) has been generally characterized by steady progression, with unpredictable relapses possibly resulting in remission. There has always been the threat of incomplete recovery during this period. Therefore, each relapse is a powerful reminder of the chronic nature of the disease, with a profound effect on the social sphere of the individual with MS. MS in general, and relapses in particular, strain the coping mechanisms of the individual and his or her family, friends, and vocational network. Recent evidence has shown that disease-modifying therapy reduces the frequency and severity of MS relapses, an important goal of MS management. Nevertheless, it is important for clinicians to be familiar with the widespread psychosocial impact of MS in terms of their patients' social involvement, partnership and family roles, and employment. PMID- 17350048 TI - Quantitative nested real-time PCR assay for assessing the clinical course of tuberculous meningitis. AB - Although the "gold standard" for diagnosis of tuberculous meningitis (TBM) is bacterial isolation of Mycobacterium tuberculosis (M. Tb), there are still several complex issues. Recently, in the diagnosis of TBM, the detection of M. Tb DNA in cerebrospinal fluid (CSF) samples using PCR has been widely performed as more rapid, sensitive, and specific diagnostic method. Based on Taq Man(R) PCR, the authors developed a novel technique of internally controlled quantitative nested real-time (QNRT) PCR assay that provided a prominent improvement in detection sensitivity and quantification. Total 43 CSF samples from 8 serial patients with suspected TBM were analyzed. The CSF samples were collected before and during standard anti-tuberculosis treatments (ATT). The QNRT-PCR assay revealed positive results for 24 out of 43 serial CSF samples (55.8%) collected during the treatment course of ATT. Moreover, the bacterial cell (BC) numbers of M. Tb analyzed by the QNRT-PCR assay decreased gradually, correlating with the improvements of the patient's clinical conditions. Since the QNRT-PCR assay provides the ability to calculate a numerical value for the initial BC numbers of M. Tb in CSF samples, this method is an extremely useful and advanced technique for use in assessing the clinical course of TBM. PMID- 17350050 TI - Synergism between hydrogen sulfide (H(2)S) and nitric oxide (NO) in vasorelaxation induced by stonustoxin (SNTX), a lethal and hypotensive protein factor isolated from stonefish Synanceja horrida venom. AB - Stonustoxin (SNTX) is a 148 kDa, dimeric, hypotensive and lethal protein factor isolated from the venom of the stonefish Synanceja horrida. SNTX (10-320 ng/ml) progressively causes relaxation of endothelium-intact, phenylephrine (PE) precontracted rat thoracic aortic rings. The SNTX-induced vasorelaxation was inhibited by L-N(G)-nitro arginine methyl ester (L-NAME), suggesting that nitric oxide (NO) contributes to the SNTX-induced response. Interestingly, D, L proparglyglycine (PAG) and beta-cyano-L-alanine (BCA), irreversible and competitive inhibitors of cystathionine-gamma-lyase (CSE) respectively, also inhibited SNTX-induced vasorelaxation, indicating that H(2)S may also play a part in the effect of SNTX. The combined use of L-NAME with PAG or BCA showed that H(2)S and NO act synergistically in effecting SNTX-induced vasorelaxation. PMID- 17350049 TI - Evolutionary graph theory: breaking the symmetry between interaction and replacement. AB - We study evolutionary dynamics in a population whose structure is given by two graphs: the interaction graph determines who plays with whom in an evolutionary game; the replacement graph specifies the geometry of evolutionary competition and updating. First, we calculate the fixation probabilities of frequency dependent selection between two strategies or phenotypes. We consider three different update mechanisms: birth-death, death-birth and imitation. Then, as a particular example, we explore the evolution of cooperation. Suppose the interaction graph is a regular graph of degree h, the replacement graph is a regular graph of degree g and the overlap between the two graphs is a regular graph of degree l. We show that cooperation is favored by natural selection if b/c>hg/l. Here, b and c denote the benefit and cost of the altruistic act. This result holds for death-birth updating, weak-selection and large population size. Note that the optimum population structure for cooperators is given by maximum overlap between the interaction and the replacement graph (g=h=l), which means that the two graphs are identical. We also prove that a modified replicator equation can describe how the expected values of the frequencies of an arbitrary number of strategies change on replacement and interaction graphs: the two graphs induce a transformation of the payoff matrix. PMID- 17350051 TI - Luminex detection of fecal indicators in river samples, marine recreational water, and beach sand. AB - Research to understand and remediate coastal pollution is moving toward a multitiered approach in which traditional enumeration of fecal indicators is accompanied by molecular analysis of a variety of targets. Technology that rapidly detects multiple microbial contaminants would benefit from such an approach. The Luminex 100 system is a suspension array that assays multiple analytes rapidly in a single well of a microtiter plate. The ability of the system to simultaneously detect multiple fecal indicating bacteria in environmental samples was tested. Primer/probe sets were designed to simultaneously detect the following fecal indicators: the Bacteroides fragilis group, Enterococcus spp., Escherichia coli and Shigella spp., Bacteroides distasonis, and Ent. faecalis. Specificity and sensitivity of the Luminex probes was tested against laboratory cultures. In addition, sequencing, culture plate testing, and specificity testing with environmental isolates were steps taken to validate the function of the assay with environmental samples. Luminex response to cultures and to environmental samples was consistent with sequencing results, suggesting that the technology has the potential to simultaneously detect multiple targets for coastal water quality applications, particularly as progress is made to efficiently extract DNA from water and sediment matrices. PMID- 17350052 TI - Gaussian approximations for phylogenetic branch length statistics under stochastic models of biodiversity. AB - Stein's method for Gaussian approximations and derived results are used to study the distribution of two phylogenetic branch length statistics: the total height of cherries and the sum of external branch lengths. The Gaussian approximations are obtained under a particular model of phylogenetic tree recently introduced by Popovic. Under an appropriate normalization the model is shown to behave similarly as the coalescent, and the approximations given here are also valid in this context. PMID- 17350053 TI - [Less invasive calibration of lumbar canal stenosis. Results with a tubular muscle retraction system used in 35 patients]. AB - BACKGROUND: The purpose of this study was to evaluate retrospectively the indications, surgical technique, and postoperative findings in a series of 35 patients presenting lumbar canal stenosis due to osteoarthritic degeneration who underwent surgery using a tubular system for muscle retraction. METHODS: This retrospective analysis included 35 patients, 28 with lumbar canal stenosis on a single level and seven with stenosis on two levels. On the stress images, 8 of these 35 patients presented stable degenerative spondylolisthesis. The surgical technique consisted in using a tubular system for muscle retraction. This enabled access for magnification and microsurgery of the canal, which was opened via an interlaminal approach. Concentric endocanal treatment was thus achieved without laminectomy. The same surgeon performed these 35 operations. The following variables were noted: patient age, level of canal narrowing, initial symptoms, duration of the operation, postoperative pain, use of analgesics, duration of hospital stay, clinical outcome at one and six months. RESULTS: The postoperative period (mean postoperative stay 2.5 days) was generally uneventful with little pain (mean VAS 0.8). This can be explained by the absence of invasive dissection. Disinsertion of the paravertebral muscles and use of elevators can induce muscle ischemia. The spine is not destabilized since laminectomy is avoided. The six month outcome showed relief of the initial symptom for 84% of patients. There were two dural breaches with no clinical impact and one patient required revision surgery because of destabilization of a degenerative spondylolisthesis. One other patient also required revision for complementary laminectomy. CONCLUSION: The short-, mid-, and long-term results of spinal canal recalibration using a less invasive approach to lumbar canal stenosis via a tubular system for muscle retraction has provided encouraging results in terms of symptom relief. The early postoperative period is short and uneventful allowing earlier resumption of daily activities. This technique reduces the cost of hospitalization and drugs and is adapted for geriatric patients. The long-term outcome with this technique should be assessed in terms of spinal stability after recalibration. PMID- 17350054 TI - Functional brain correlates of response time variability in children. AB - During tasks requiring response inhibition, intra-individual response time variability, a measure of motor response preparation, has been found to correlate with errors of commission, such that individuals with higher variability show increased commission errors. This study used fMRI to examine the neural correlates of response variability in 30 typically developing children, ages 8 12, using a simplified Go/No-go task with minimal cognitive demands. Lower variability was associated with Go activation in the anterior cerebellum (culmen) and with No-go activation in the rostral supplementary motor area (pre-SMA), the postcentral gyrus, the anterior cerebellum (culmen) and the inferior parietal lobule. For both Go and No-go events, higher variability was associated with activation in prefrontal cortex and the caudate. The findings have implications for neuropsychiatric disorders such as ADHD and suggest that during response inhibition, children with more consistent performance are able to rely on premotor circuits involving the pre-SMA, important for response selection; those with less consistent performance instead recruit prefrontal circuits involved in more complex aspects of behavioral control. PMID- 17350055 TI - Volitional control of food transport and bolus formation during feeding. AB - When healthy individuals eat solid food, chewed food is usually transported to the oropharynx where it accumulates before swallowing (stage II transport). We tested the hypothesis that this transport process can be altered by volition. Eight healthy young subjects ate 8 g pieces of cookie with barium while movements were recorded with videofluorography. There were two trials for each subject, each with different instructions: 1) without command: to eat the cookie in his/her usual manner; 2) with command: to chew the cookie, give a signal when ready to swallow, and then swallow on command of the investigator. We measured the number of chewing cycles, the duration of each stage in the feeding sequence, and the position of the leading edge of the barium at time of command and at swallow onset. Sequence duration was longer with than without command (P=0.02), primarily because of an increase in the number of chewing cycles (P=0.02). The leading edge was typically higher in the foodway at the time of swallow onset with than without command (P=0.06). Under the command condition, stage II transport was delayed, and transport to the valleculae was inhibited. Volition alters swallow initiation in both the timing and location of the food bolus relative to the airway. PMID- 17350056 TI - [Solitary bony plasmocytoma of the mandible]. AB - INTRODUCTION: Solitary plasmocytoma is a rare malignant tumor, belonging to the larger family of plasma cell proliferative diseases observed in bones. The mandible localization reported here is extremely rare. CASE REPORT: A 57-year-old man consulted for a tumefaction of the right mandible. Physical examination revealed a mandibular tumor with an osseous consistency covered by a healthy mucous. Radiologically, the tissue processed from the mandible, which presented a defect and an eroded cortical. Hemimandibulectomy was performed. Pathologic examination of the operative specimen demonstrated plasmocytoma. Complementary radiotherapy was performed. Outcome at 13 months was favorable, without recurrence of multiple myeloma. DISCUSSION: Plasma cell tumors are rare, about 10% of them are solitary plasmocytomas observed in intra- or extramedullar sites. Pathology is required for confirmation. An exhaustive assessment is needed to rule out multiple myeloma. Most solitary forms are observed in the spine. Appropriate treatment combines surgery and radiotherapy. Careful surveillance is required because of the frequent progression to multiple myeloma. PMID- 17350057 TI - [Antenatal diagnosis of rapidly involuting congenital hemangiomas (RICH)]. AB - INTRODUCTION: Since 1996, vascular anomalies are classified either as tumors or malformations. Infantile hemangioma is the most common vascular tumor. It is an endothelial cellular proliferation, stimulated after birth (10th day) which then slow involves. Congenital hemangioma is a different kind of hemangioma develops prenatally appearing fully grown at birth. Rapidly involuting congenital hemangioma (RICH) generally involutes spontaneously while non involuting congenital hemangioma (NICH) usually requires a surgical procedure. The clinical and radiological aspects of these two tumors differ significantly at birth. Most congenital hemangiomas detected at antenatal ultrasonography, due to their cephalic localization and their size (up to 10 cm) are RICH. MATERIAL AND METHODS: We report on five vascular tumors detected in utero during the second and third trimesters, and after birth. RESULTS: There were three boys and two girls. The average size of the RICH was 5 cm (1.8-10 cm). Four were cephalic and one on a lower limb. A doppler examination was available in three patients, and showed fast-flow in two. Prenatal magnetic resonance imaging was available in three patients. DISCUSSION: The diagnosis of RICH can be suspected on the antenatal ultrasonography. Fast-flow on the doppler examination confirms the diagnosis. It is advisable to repeat the ultrasonography every two to four weeks to reevaluate the possibility of delivery and the fetal cardiac status. In the event of a prenatal vascular tumor the differential diagnosis also includes other congenital tumors. Magnetic resonance imaging would be indicated if there is any doubt about malignancy. Regular follow-up is necessary during the first months to confirm the diagnosis. RICH regress rapidly while the size of malignant tumors increases. A biopsy is necessary to obtain histopatholgical proof. PMID- 17350058 TI - [An unusual jugal abscess after third molar extraction: a complication of hemostatic wax]. AB - Bleeding is a common complication after third molar extraction. Hemostatic agents can be helpful in controlling intraoperative bleeding. Infection is another common complication. Horseley's wax is frequently used for bone surgery and less often for dental surgery. We report an unusual case of abscess formation in the jaw after third molar extraction. Surgical exploration of the abscess disclosed the presence of surgical wax in the center of a foreign body granuloma. We discuss the use of surgical wax and other local hemostatic agents and the subsequent risk of complications. PMID- 17350059 TI - [Mesenchymal chondrosarcoma of the mandible]. AB - INTRODUCTION: Mesenchymal chondrosarcoma is a rare form of chondrosarcoma and mandibular localization is rare. OBSERVATION: We report a case of mesenchymal chondrosarcoma of the mandible in a 23-year-old patient who consulted for a voluminous tumor of the right mandible. Radiological findings suggested a malignant tumor. A hemimandibulectomy and a pelvectomy were performed. The histological assessment showed zones of neoplastic cartilage and small ovoid cells, typical of mesenchymal chondrosarcoma. DISCUSSION: Mesenchymal chondrosarcoma is a rare malignant tumor of skeletal and extra skeletal origin. The most frequent localizations are the femur, the ribs, and facial bones. Histologically, these tumors have a typical biphasic pattern consisting of both small cells and islands of atypical cartilage. Because of its rich vascular component, this lesion has often been confused with hemangiopericytoma. Surgery is the usual treatment. The prognosis is very poor with a high risk of relapse and metastasis. PMID- 17350060 TI - Dynamics of escape mutants. AB - We use multi-type Galton-Watson branching processes to model the evolution of populations that, due to a small reproductive ratio of the individuals, are doomed to extinction. Yet, mutations occurring during the reproduction process, may lead to the appearance of new types of individuals that are able to escape extinction. We provide examples of such populations in medical, biological and environmental contexts and give results on (i) the probability of escape/extinction, (ii) the distribution of the waiting time to produce the first individual whose lineage does not get extinct and (iii) the distribution of the time it takes for the number of mutants to reach a high level. Special attention is dedicated to the case where the probability of mutation is very small and approximations for (i)-(iii) are derived. PMID- 17350061 TI - Transplacental exposure to inorganic arsenic at a hepatocarcinogenic dose induces fetal gene expression changes in mice indicative of aberrant estrogen signaling and disrupted steroid metabolism. AB - Exposure to inorganic arsenic in utero in C3H mice produces hepatocellular carcinoma in male offspring when they reach adulthood. To help define the molecular events associated with the fetal onset of arsenic hepatocarcinogenesis, pregnant C3H mice were given drinking water containing 0 (control) or 85 ppm arsenic from day 8 to 18 of gestation. At the end of the arsenic exposure period, male fetal livers were removed and RNA isolated for microarray analysis using 22K oligo chips. Arsenic exposure in utero produced significant (p<0.001) alterations in expression of 187 genes, with approximately 25% of aberrantly expressed genes related to either estrogen signaling or steroid metabolism. Real-time RT-PCR on selected genes confirmed these changes. Various genes controlled by estrogen, including X-inactive-specific transcript, anterior gradient-2, trefoil factor-1, CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over expressed. Estrogen-regulated genes including cytokeratin 1-19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed. Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17beta-hydroxysteroid dehydrogenase-7 (HSD17beta7; involved in estradiol production) and decreased expression of HSD17beta5 (involved in testosterone production). The expression of key genes important in methionine metabolism, such as methionine adenosyltransferase-1a, betaine-homocysteine methyltransferase and thioether S-methyltransferase, were suppressed. Thus, exposure of mouse fetus to inorganic arsenic during a critical period in development significantly alters the expression of various genes encoding estrogen signaling and steroid or methionine metabolism. These alterations could disrupt genetic programming at the very early life stage, which could impact tumor formation much later in adulthood. PMID- 17350062 TI - Interacting influence of potassium and polychlorinated biphenyl on cortisol and aldosterone biosynthesis. AB - Giving human adrenocortical H295R cells 14 mM KCl for 24 h significantly induced not only aldosterone biosynthesis but also cortisol biosynthesis. Pre-treating the cells with polychlorinated biphenyl 126 (PCB126) further increased potassium induced aldosterone and cortisol productions in a dose-dependent manner, but all examined concentrations of PCB126 had little effect on the yields of precursor steroids progesterone and 17-OH-progesterone. Subsequent examinations revealed that CYP11B1 and CYP11B2 genes, responsible for the respective final steps of the cortisol and aldosterone biosynthetic pathways, exhibited increased responsiveness to PCB126 under high potassium. While 10(-5) M PCB126 was needed to induce a significant increase in the basal mRNA abundance of either gene, PCB126 could enhance potassium-induced mRNA expression of CYP11B1 at 10(-7) M and CYP11B2 at 10(-9) M. Actually, potassium and PCB126 synergistically upregulated mRNA expression of both genes. Potassium raised the transcriptional rates of CYP11B1 and CYP11B2 probably through a conserved Ad5 cis-element, whereas PCB126 appeared to regulate these two genes at the post-transcriptional level. Positive potassium-PCB126 synergism was also detected in CYP11B2 enzyme activity estimated by aldosterone/progesterone ratio. In contrast, potassium and PCB126 increased CYP11B1 enzyme activity or cortisol/17-OH-progesterone ratio additively. Moreover, potassium improved the time effect of PCB126 on gene expression and enzyme activity of CYP11B2, but not the PCB126 time response of CYP11B1. These data demonstrated that potassium differentially enhanced the potency of PCB126 to induce CYP11B1- and CYP11B2-mediated steroidogenesis. PMID- 17350063 TI - Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology. AB - PURPOSE: In the present study, diffusion-weighted magnetic resonance imaging (DW MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. METHODS: Three hours and 24 h after the intoxication with soman (172 microg/kg), the mice were anesthetized with an isoflurane/N(2)O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. RESULTS: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication and was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. CONCLUSIONS: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into the brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures. PMID- 17350064 TI - Microarray analysis of the AHR system: tissue-specific flexibility in signal and target genes. AB - Data mining published microarray experiments require that expression profiles are directly comparable. We performed linear global normalization on the data of 1967 Affymetrix U74av2 microarrays, i.e. the transcriptomes of >100 murine tissues or cell types. The mathematical transformation effectively nullifies inter experimental or inter-laboratory differences between microarrays. The correctness of expression values was validated by quantitative RT-PCR. Using the database we analyze components of the aryl hydrocarbon receptor (AHR) signaling pathway in various tissues. We identified lineage and differentiation specific variant expression of AHR, ARNT, and HIF1alpha in the T-cell lineage and high expression of CYP1A1 in immature B cells and dendritic cells. Performing co-expression analysis we found unorthodox expression of the AHR in the absence of ARNT, particularly in stem cell populations, and can reject the hypothesis that ARNT2 takes over and is highly expressed when ARNT expression is low or absent. Furthermore the AHR shows no co-expression with any other transcript present on the chip. Analysis of differential gene expression under 308 conditions revealed 53 conditions under which the AHR is regulated, numerous conditions under which an intrinsic AHR action is modified as well as conditions activating the AHR even in the absence of known AHR ligands. Thus meta-analysis of published expression profiles is a powerful tool to gain novel insights into known and unknown systems. PMID- 17350065 TI - Non-invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity. AB - Gliosis is a universal response of the brain to almost all types of neural insults, including neurotoxicity, neurodegeneration, viral infection, and stroke. A hallmark of gliotic reaction is the up-regulation of the astrocytic biomarker GFAP (glial fibrillary acidic protein), which often precedes the anatomically apparent damages in the brain. In this study, neonatal transgenic mice at postnatal day (PD) 4 expressing GFP (green fluorescent protein) under the control of a widely used 2.2-kb human GFAP promoter in the brain are treated with two model neurotoxicants, 1-methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2' CH(3)-MPTP), and kainic acid (KA), respectively, to induce gliosis. Here we show that the neurotoxicant-induced acute gliosis can be non-invasively imaged and quantified in the brain of conscious (un-anesthetized) mice in real-time, at 0, 2, 4, 6, and 8 h post-toxicant dosing. Therefore the current methodology could be a useful tool for studying the developmental aspects of neuropathies and neurotoxicity. PMID- 17350066 TI - Ostreolysin affects rat aorta ring tension and endothelial cell viability in vitro. AB - The effects of ostreolysin, a cardiotoxic cytolysin produced by the edible oyster mushroom (Pleurotus ostreatus), were studied on tension development in isolated rat aortic ring. Its cytotoxic effects on human umbilical vein endothelial cells and Chinese hamster lung fibroblasts were also studied. Ostreolysin induced a concentration-dependent increase in aortic ring tension in the range from 5 to 30 microg/ml, and was cytotoxic to both cell lines. These effects could contribute significantly to its previously observed cardiotoxicity. PMID- 17350068 TI - Feature-based processing of audio-visual synchrony perception revealed by random pulse trains. AB - Computationally, audio-visual temporal synchrony detection is analogous to visual motion detection in the sense that both solve the correspondence problem. We examined whether audio-visual synchrony detection is mediated by a mechanism similar to low-level motion sensors, by one similar to a higher-level feature matching process, or by both types of mechanisms as in the case of visual motion detection. We found that audio-visual synchrony-asynchrony discrimination for temporally dense random pulse trains was difficult, whereas motion detection is known to be easy for spatially dense random dot patterns (random dot kinematograms) due to the operation of low-level motion sensors. Subsequent experiments further indicated that the temporal limiting factor of audio-visual synchrony discrimination is the temporal density of salient features not the temporal frequency of the stimulus, nor the physical density of the stimulus. These results suggest that audio-visual synchrony perception is based solely on a salient feature matching mechanism similar to that proposed for high-level visual motion detection. PMID- 17350067 TI - A TRIM5alpha-independent post-entry restriction to HIV-1 infection of macaque cells that is dependent on the path of entry. AB - The replication of human immunodeficiency type-1 (HIV-1) is restricted in macaque cells, in part due to host factors that provide intrinsic immunity after entry. Here we show that a rhesus macaque epithelial cell line engineered to express human CD4, sMAGI cells, has at least two post-entry restrictions to HIV-1 replication: one that is dependent on a previously described post-entry restriction factor of macaque cells, TRIM5alpha, and another that is primarily TRIM5alpha-independent. The TRIM5alpha restriction, which was observed with particles that had an HIV-1 core pseudotyped with VSV-G envelope, is saturable and can be completely abrogated by introducing TRIM5alpha-specific siRNA into the cells. A similar TRIM5alpha-dependent restriction was observed when sMAGI cells expressing human CCR5 were infected with an R5-HIV-1. In contrast, even when viruses enter sMAGI cells using CD4 and an endogenous rhesus coreceptor at levels sufficient to saturate TRIM5alpha, they do not productively infect the sMAGI cells. Nor does treatment of sMAGI cells with TRIM5alpha-specific siRNA relieve this post-entry restriction; this was true whether the HIV-1 core was pseudotyped with SIV envelope or an R5-HIV-1 envelope. Together these data suggest that there is an alternate restriction to replication, here called Lv3, that is encountered by viruses that enter via interaction with CD4 and an endogenous rhesus coreceptor. Thus, these findings suggest that post-entry events are dependent upon the mechanism by which HIV-1 enters the cell. PMID- 17350069 TI - Effects of trial repetition in texture discrimination. AB - Performance on the texture discrimination task improves with practice but was also shown to decrease between closely spaced sessions. Here we explored immediate changes in performance within a single session. We found that, after an initial increase, performance declined with further training within a single session. This deterioration in performance was smaller when the inter-trial interval was longer than 3s. Performance recovered when targets were presented in new locations within the texture stimulus-thereby excluding a general fatigue process or adaptation to the stimulus light-intensity as an explanation for our findings. Further, the complete transfer of deterioration between eyes pointed to cortical origin. Deterioration was also found for task-irrelevant targets, indicating the involvement of a sensory mechanism. Collectively, these findings trace the deterioration of performance in the texture discrimination task, previously observed across several hours, to cortical events occurring during or immediately after stimulus presentation. PMID- 17350070 TI - Recovery from axial myopia induced by a monocularly deprived facemask in adolescent (7-week-old) guinea pigs. AB - PURPOSE: Guinea pigs have been increasingly used as an animal model for experimental myopia. Infant guinea pigs are susceptible to recovery from myopia within 2 weeks of form deprivation. This study investigated whether adolescent guinea pigs are susceptible to recovery from myopia after a longer period of form deprivation. METHOD: Twenty-two guinea pigs (age of 3 weeks) were randomly assigned to two groups: MDF (monocularly deprived facemask, n=11) and normal control (free of form deprivation, n=11). All animals underwent biometric measurement (refraction, corneal curvature and axial length) prior to the experiment. Animals in the MDF group wore a facemask that covered the right eye for 4 weeks. The MDF was then removed and biometric measurement was performed immediately and at 2, 6, 10 and 14 days. The same measurement was performed in the normal control group at time-points matching those of the MDF group. RESULTS: The MDF eyes were approximately 4D more myopic with a greater increase in vitreous length by 0.12 mm compared to either the fellow or the normal control eyes after form deprivation (p<0.01). This relative myopia shifted rapidly towards hyperopia within 2 days after removal of the MDF, followed by a more gradual recovery. A complete recovery occurred by 6 days after removal of the MDF compared to the fellow and normal control eyes (p>0.05). Vitreous length in the MDF eyes slightly reduced within 2 days after removal of the MDF and then remained steady. The MDF eyes were similar to both the fellow and normal control eyes in vitreous length (p>0.05) 6 days after removal of the MDF. There was no significant difference between the MDF, fellow and normal control eyes in the other axial components during the form deprivation and recovery period. CONCLUSION: Adolescent guinea pigs are susceptible to recovery from MDF-induced myopia. The refractive recovery is mainly correlated to the inhibited axial elongation of the vitreous chamber of the previously deprived eyes. PMID- 17350071 TI - Specific alterations of tyrosine hydroxylase immunopositive cells in the retina of NT-4 knock out mice. AB - To assess the effect of NT-4 deprivation on maturation of retinal circuitry, we investigated a mouse with targeted deletion of the gene encoding nt-4 (nt-4(-/ )). In particular, we studied neurons immunostained by an antibody recognizing tyrosine hydroxylase (TH), the rate limiting enzyme for dopamine (DA) synthesis. We found that TH immunopositive processes were altered in the retina of nt-4(-/ ). Alteration of TH immunopositive processes in nt-4(-/-) mice resulted in changes of DA turnover, as assessed by high-pressure liquid chromatography measurements. These findings suggest that retinal NT-4 plays a role in the morphological maturation of dopaminergic retinal cells. PMID- 17350072 TI - Density effects on activated sludge zone settling velocities. AB - A recently developed method to manipulate biomass density based on the addition of synthetic microspheres was used to isolate density effects on zone (hindered) settling velocities in samples from full-scale activated sludge plants over a range biomass densities and concentrations. Settling velocities increased by as much as a factor of five as density was increased by microsphere addition. The effects of density on the Vesilind sedimentation model parameters (V=V(o)e(-kX) , where V is the settling velocity, X is the biomass concentration, and V(o) and k are constants) were evaluated. The parameter V(o) was positively correlated with density for values greater than approximately 1.02 g/mL, while k values were approximately constant in this range. New models were developed for settling velocity as a function of both density and biomass concentration, and these may be useful for future incorporation with clarifier models to improve predictions of system performance, particularly when biomass characteristics known to affect density are variable, such as polyphosphate and nonvolatile suspended solids content. PMID- 17350073 TI - Development of high-rate anaerobic ammonium-oxidizing (anammox) biofilm reactors. AB - To promptly establish anaerobic ammonium oxidation (anammox) reactors, appropriate seeding sludge with high abundance and activity of anammox bacteria was selected by quantifying 16S rRNA gene copy numbers of anammox bacteria by real-time quantitative PCR (RTQ-PCR) and batch culture experiments. The selected sludge was then inoculated into up-flow fixed-bed biofilm column reactors with nonwoven fabric sheets as biomass carrier and the reactor performances were monitored over 1 year. The anammox reaction was observed within 50 days and a total nitrogen removal rate of 26.0 kg-Nm(-3)day(-1) was obtained after 247 days. To our knowledge, such a high rate has never been reported before. Hydraulic retention time (HRT) and influent NH(4)(+) to NO(2)(-) molar ratio could be important determinant factors for efficient nitrogen removal in this study. The higher nitrogen removal rate was obtained at the shorter HRT and higher influent NH(4)(+)/NO(2)(-) molar ratio. After anammox reactors were fully developed, the community structure, spatial organization and in situ activity of the anammox biofilms were analyzed by the combined use of a full-cycle of 16S rRNA approach and microelectrodes. In situ hybridization results revealed that the probe Amx820 hybridized anaerobic anammox bacteria were distributed throughout the biofilm (accounting for more than 70% of total bacteria). They were associated with Nitrosomonas-like aerobic ammonia-oxidizing bacteria (AAOB) in the surface biofilm. The anammox bacteria present in this study were distantly related to the Candidatus Brocadia anammoxidans with the sequence similarity of 95%. Microelectrode measurements showed that a high in situ anammox activity (i.e., simultaneous consumption of NH(4)(+) and NO(2)(-)) of 4.45 g-N of (NH(4)(+)+NO(2)(-))m(-2)day(-1) was detected in the upper 800 microm of the biofilm, which was consistent with the spatial distribution of anammox bacteria. PMID- 17350074 TI - Solar-based detoxification of phenol and p-nitrophenol by sequential TiO2 photocatalysis and photosynthetically aerated biological treatment. AB - Simulated solar UV/TiO(2) photocatalysis was efficient to detoxify a mixture of 100 mgphenoll(-1) and 50 mgp-nitrophenol (PNP) l(-1) and allow the subsequent biodegradation of the remaining pollutants and their photocatalytic products under photosynthetic aeration with Chlorella vulgaris. Photocatalytic degradation of phenol and PNP was well described by pseudo-first order kinetics (r(2)>0.98) with removal rate constants of 1.9x10(-4) and 2.8x10(-4)min(-1), respectively, when the pollutants were provided together and 5.7x10(-4) and 9.7x10(-4)min(-1), respectively, when they were provided individually. Photocatalytic pre-treatment of the mixture during 60 h removed 50+/-1% and 62+/-2% of the phenol and PNP initially present but only 11+/-3% of the initial COD. Hydroquinone, nitrate and catechol were identified as PNP photocatalytic products and catechol and hydroquinone as phenol photocatalytic products. Subsequent biological treatment of the pre-treated samples removed the remaining contaminants and their photocatalytic products as well as 81-83% of the initial COD, allowing complete detoxification of the mixture to C. vulgaris. Similar detoxification efficiencies were recorded after biological treatment of the irradiated mixture with activated sludge microflora or with an acclimated consortia composed of a phenol-degrading Alcaligenes sp. and a PNP-degrading Arthrobacter sp., although the acclimated strains biodegraded the remaining pollutants faster. Biological treatment of the non-irradiated mixture was inefficient due to C. vulgaris inhibition. PMID- 17350075 TI - Fermentation of agro-food wastewaters by activated sludge. AB - This study investigates the potential of agro-food wastewater fermentation by activated sludge. Experimental results shown that all of the agro-food wastewaters studied initially had considerable concentrations of fermentable substrates, ranging from 19% to 68% of the total COD, but not all of the substrates contained in this COD fraction were fermented after an anaerobic stage of 10h. The percentage of fermentable substrates fermented by the activated sludge during the anaerobic stage ranged from 14% to 68%, presenting the potato processing wastewater the highest concentration of fermented substrates. A mathematical model was proposed to describe the fermentation process. By using this model, the maximum fermentation rates were obtained, ranging their values from 0.6 to 3.4 (gCODgCOD(-1)d(-1)). The fermentation potentials of the agro-food wastewaters were also determined, their values ranged from 0.17 to 0.20 (gCODgCOD(-1)) except for the cheese and the winery wastewater which presented fermentation potentials of 0.12 and 0.14 (gCODgCOD(-1)), respectively. PMID- 17350076 TI - Fluorescence characterization of cross flow ultrafiltration derived freshwater colloidal and dissolved organic matter. AB - 3-D fluorescence excitation-emission matrix (EEM) spectrophotometry was applied to investigate the fluorescence characterization of colloidal organic matter (COM) and truly dissolved organic matter (DOM) from an urban lake and a rural river fractionated by the cross flow ultrafiltration (CFUF) process with a 1kDa membrane. Relatively high tryptophan-like fluorescence intensity is found in the urban water, although the fluorescence of both water samples is mainly dominated by humic/fulvic-like fluorophores. During CFUF processing, the fluorescence intensities of humic/fulvic-like materials in the retentate increased rapidly, but a slight increase is also observed in the permeate fluorescence intensity. Very different ultrafiltration behaviour occurred with respect to the tryptophan like fluorophore, where both permeate and retentate fluorescence intensities increase substantially at the beginning of the CFUF process, then tend to remain constant at high concentration factor (cf) values. Comparison with tryptophan standards demonstrates that freshwater tryptophan-like fluorescence is not dissolved and 'free', but is, in part, colloidal and related to the ultrafiltration behaviour of fulvic/humic-like matter. A good linear relationship between the retentate humic/fulvic-like fluorescence intensity and organic carbon concentration further reveals that fluorescent humic/fulvic-like substances are the dominant contributors to colloidal organic carbon, mainly in the colloidal fraction. PMID- 17350077 TI - Influence of the presence of heavy metals and surface-active compounds on the sorption of bisphenol A to sediment. AB - The effects of different heavy metals (Cd, Pb), cationic surfactants cetyltrimethylammonium bromide (CTAB), anionic surfactant sodium dodecylbenzenesulfonate (SDBS) and the chemistry of the solution (pH and ionic strength) on the sorption of bisphenol A (BPA) to sediment were studied. Results showed that the presence of Cd and Pb caused a significant increase on the sorption of BPA to sediment and the sorption isotherms were in good agreement with Freundlich equation. The effect of surfactants on the adsorption of BPA onto sediment was found to strongly depend on the type of the surfactants. The presence of CTAB promoted BPA sorption and the amount of BPA adsorbed onto sediment increased linearly with concentration of CTAB. In contrast, the presence of anionic surfactant (SDBS) caused a slight reduction on the sorption of BPA. It was also found that the sorption behavior of BPA was affected by solution pH and ionic strength. The larger amount of BPA was absorbed with higher ionic strength and lower pH. This study may provide important insights into the understanding of the transport and fate of BPA in the environment. PMID- 17350078 TI - Dynamics of metal tolerant plant communities' development in mine tailings from the Cartagena-La Union Mining District (SE Spain) and their interest for further revegetation purposes. AB - Mine tailings are typical elements in post-mining landscapes which usually have high heavy metal contents and are affected by intensive erosion processes, above all in arid and semiarid areas. Revegetation of these sites is considered a low cost and suitable technology to effect surface stabilization. Spontaneous plant communities that colonize tailings in Southern Spain showed different behavior depending on the pH: in neutral tailings the plant communities were formed by less number of plant species than in acid tailings but they had less seasonal variations, showing a stable development. This spontaneous vegetation, that is adapted to metal toxicity and to drought, allows reducing air borne and water erosion, and may mitigate the spread of the contamination to the nearby areas. PMID- 17350079 TI - Bioaccumulation, bioavailability and environmental fate of chlorophenol impurities, polychlorinated hydroxydiphenylethers and their methoxy analogues. AB - The bioaccumulation potential and environmental fate of polychlorinated hydroxydiphenyl ethers (HO-PCDEs; polychlorinated phenoxyphenols, PCPP), the major impurities of chlorophenol formulations and their methoxy analogues (MeO PCDEs; polychlorinated methoxyanisoles, PCPAs) were investigated. Oligochaete worms (Lumbriculus variegatus) exposed to sediment spiked with a model substance of one HO-hexaCDE (4'-HO-PCDE 161) or its methoxy analogue (4'-MeO-PCDE 161) clearly accumulated the test compounds revealing the potential for environmental risk of HO-PCDEs and MeO-PCDEs. The HO-PCDE tested has earlier been reported as an abundant component in a Finnish chlorophenol formulation (Ky-5) and its methoxy analogue is recognized as an abundant MeO-PCDE in sawmill soil contaminated by the formulation. The occurrence of 4'-HO-PCDE 161 and its methoxy analogue among other HO-PCDEs and MeO-PCDEs in lake mussels (Anodonta piscinalis) incubated in a river contaminated via the manufacture of Ky-5 showed that these compounds are bioavailable and transported in the aquatic environment. Mussel comparison with sediment data pointed to a higher accumulation potential for MeO PCDEs than for HO-PCDEs. The finding of HO-PCDEs in groundwater samples collected from a groundwater reservoir, which had been contaminated by chlorophenols, points to potential of HO-PCDEs for transport with water in soil. PMID- 17350080 TI - Biogenic sulphide plays a major role on the riboflavin-mediated decolourisation of azo dyes under sulphate-reducing conditions. AB - The effect of high concentrations of sulphate on the reductive decolourisation of different azo dyes by anaerobic sludge was studied in batch cultures. Sludge cultures were pre-incubated under sulphate-reducing conditions prior addition of dyes. Little or no effects of sulphate (5-10 g sulphate l(-1)) on the rate of decolourisation of Reactive Orange 14 (RO14), Direct Blue 53 (DB53) and Direct Blue 71 (DB71) were observed when no external redox mediator was provided. However, an increase in sulphate concentration, in the presence of riboflavin (20 microM), enhanced the decolourisation of all dyes. The first-rate constant of decolourisation (k) was increased up to 2-, 3.6- and 2-fold for RO14, DB53 and DB71, respectively, by supplying high sulphate concentrations, compared to the controls lacking sulphate, in the presence of the redox mediator. Sulphate reduction did not take place during the course of azo reductions, but was only evident before dye addition and after complete decolourisation, suggesting azo dyes reduction out-competed sulphate reduction for the available reducing equivalents. The experimental data suggest that reduction of azo dyes by riboflavin, which had been reduced by biogenic sulphide, was the major mechanism implicated during decolourisations, which was corroborated by abiotic incubations. Riboflavin greatly accelerated the abiotic reduction of RO14, so that the k value was increased up to 44-fold compared to the control lacking riboflavin. PMID- 17350081 TI - Expression of inhibitor-of-apoptosis protein family members in malignant mesothelioma. AB - Inhibitor-of-apoptosis proteins (IAPs) mediate cancer cell survival and chemoresistance. We analyzed the expressions of X-linked IAP (XIAP), survivin, and livin in malignant mesothelioma. Ten effusions were analyzed for XIAP, survivin, and livin expression using immunoblotting. Based on the immunoblotting results, 112 mesotheliomas from 94 patients (pleural, n = 77; peritoneal, n = 35; solid, n = 68; effusions, n = 44) were immunostained for XIAP and survivin expression. Results were analyzed for associations with anatomic site (pleura versus peritoneum), specimen type (solid versus effusion), proliferation (Ki-67 score), and survival. Immunoblotting showed expression of XIAP in 9 of 10 effusions and that of survivin in 4 of 10 effusions, but no expression of livin. Immunohistochemistry showed cytoplasmic XIAP expression in 71 of the 112 (63%) tumors. XIAP expression was significantly higher in peritoneal mesotheliomas than in pleural mesotheliomas (P = .001) and in effusions than in solid lesions (P = .017). Cytoplasmic survivin was found in 75 of the 112 (67%) tumors and showed no site-related difference. Nuclear survivin was expressed in 37 of the 112 (33%) tumors, with a trend for positive association with the Ki-67 score (P = .051). Nuclear survivin (P = .003) and Ki-67 (P = .013) were downregulated in effusions as compared with solid tumors. Higher XIAP expression and Ki-67 score were associated with a trend for poor overall survival (P = .064 for both) in the univariate analysis. XIAP and survivin, but not livin, are frequently expressed in malignant mesotheliomas. Nuclear survivin expression is reduced in effusions as compared with solid lesions concomitantly with reduced proliferation. XIAP is upregulated in mesothelioma effusions and peritoneal mesotheliomas, suggesting a prosurvival role in malignant mesothelioma cells, particularly at these anatomic sites. PMID- 17350082 TI - A clinical algorithm to predict the loading dose of phenprocoumon. PMID- 17350083 TI - MMP-13 (collagenase 3) immunolocalisation during initial orthodontic tooth movement in rats. AB - Matrix metalloproteinases (MMPs) are enzymes that play a central role in periodontal ligament (PDL) space remodelling during orthodontic tooth movement. It has previously been shown that messenger RNA levels of MMP-13 increase significantly following the application of orthodontic forces. The aim of the present study was to examine immunolocalisation of MMP-13 and to evaluate if this collagenase is time-dependently and differentially detected within the PDL following the application of orthodontic forces to create areas of compression and tension. This was achieved by placing elastic bands between the maxillary first and second molars of 16 male Sprague-Dawley rats (each weighing 120-200g) for 12 and 24h. The molar-bearing segments were dissected and processed for histological and immunohistochemical examination. Binding of a monoclonal antibody was used to evaluate MMP-13 localization using an indirect streptavidin/biotin immunperoxidase technique. MMP-13 was found to be inducible at the protein level by the application of forces. The PDL and osteoblast-lineage cells showed a time-dependent increase in immunolabelling of MMP-13. Immunolabelling of MMP-13 was detected initially on the compression side, and then on both the compression and the tension sides. Since this increase in MMP-13 immunolabelling occurred very early following the application of an orthodontic force in both PDL and alveolar bone, this would indicate that MMP-13 might play an important role during tooth movement. PMID- 17350084 TI - NMDA receptor in conditioned flavor-taste preference learning: blockade by MK-801 and enhancement by D-cycloserine. AB - Conditioned flavor-taste preference (CFTP) is a robust form of learning in which animals acquire a preference for a flavor (e.g. Kool-Aid) previously mixed with a highly preferred tastant (e.g. fructose) over a flavor previously mixed with a less-preferred tastant (e.g. saccharin). Here, the role of the N-methyl-D aspartate (NMDA) glutamate-glycine receptor (NR) was probed using systemic MK 801, a non-competitive antagonist, and D-cycloserine (DCS), a glycine agonist. Rats were injected with MK-801 (100 microg/kg) or vehicle 30 min prior to a daily 2-h conditioning session with 1-bottle access to a Kool-Aid flavor (grape or cherry) mixed with either 8% fructose (CS+/F) or 0.2% saccharin (CS-/S). CFTP expression was measured in 2-bottle preference tests between the Kool-Aid flavors mixed with 0.2% saccharin (CS+/S vs. CS-/S). While vehicle-treated rats acquired a preference for CS+/S over CS-/S, MK-801 prior to conditioning completely blocked CFTP learning. The effect of MK-801 was specific to CFTP acquisition, because follow-up experiments demonstrated that MK-801 did not induce a conditioned taste aversion, cause state-dependent learning, or affect CFTP expression. In a second approach, rats were injected with DCS (15 mg/kg) 60 min prior to daily conditioning. In contrast to MK-801, administration of DCS prior to conditioning enhanced CFTP learning (but not reversal conditioning). These results demonstrate that NR neurotransmission is critical for CFTP learning. Furthermore, enhancement of CFTP learning by DCS suggests that endogenous levels of glycine or D-serine may be a limiting factor in CFTP learning. PMID- 17350085 TI - Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults; the accuracy of the MedDietScore. AB - OBJECTIVE: We sought to evaluate the accuracy of a diet score in relation to hypertension, hypercholesterolemia, diabetes and obesity. METHODS: A diet score (range 0-55) has been developed that assesses adherence to the Mediterranean diet. For the consumption of items presumed to be close to Mediterranean dietary pattern (non-refined cereals, fruits, vegetables, legumes, olive oil, fish and potatoes) scores 0 to 5 for never, rare, frequent, very frequent, weekly and daily consumption were assigned, while for the consumption of foods presumed to be away from this pattern (red meat and products, poultry and full fat dairy products) scores on a reverse scale were assigned. Positive and negative predictive values, in relation to hypertension, hypercholesterolemia, diabetes and obesity status of the ATTICA study participants (n=3042, enrolment 2001-02 in Athens metropolitan area, aged 18-89 years) were calculated and the 10-year CHD risk based on Framingham equations was estimated, too. RESULTS: The positive predictive values of the score regarding hypertension, hypercholesterolemia, diabetes and obesity are: 45% (95% CI 43%-48%), 46% (95% CI 44%-49%), 12% (95% CI 11%-14%) and 33% (95% CI 30%-35%), while the negative predictive values are 86% (95% CI 85%-88%), 71% (95% CI 69%-74%), 98% (95% CI 97%-99%) and 97% (95% CI 96% 98%), respectively. Moreover, a 10-unit increase in the diet score is associated with 4% lower 10-year CHD risk (+/-0.1%, p<0.001). CONCLUSION: The proposed Mediterranean Diet Score may be useful in detecting individuals prone to the development of nutrition-related health conditions and cardiovascular disease. PMID- 17350086 TI - Impact of disease management on health care utilization: evidence from the "Florida: A Healthy State (FAHS)" Medicaid Program. AB - OBJECTIVE: To examine the impact of disease management on utilization of selected health care services. METHOD: Prospective observational population-based study comparing Florida Medicaid patients who elected to participate in disease management (DM, N=15,275) with a usual-care (UC, N=32,034) group who elected not to participate in the program. Patients had at least one of four chronic diseases (diabetes, asthma, congestive heart failure, and hypertension) and all received standard health care. DM participants received supplementary telephone health counseling by a managed care specialist. The data for this paper were collected between October 2001 and October 2004. RESULTS: Annual rates of inpatient hospital stays, inpatient days, emergency room (ER) visits, and outpatient (OP) visits, during and post intervention, were used as outcomes. Age, race, gender, comorbidities, severity indicators, geographic location and pre-intervention utilization were used as covariates. Compared to UC patients, DM patients had lower adjusted post intervention annualized rates of hospitalizations ranging from 0.07 to 0.38 stays, lower rates of hospital days ranging from 0.40 to 2.54 days, and lower rates of ER visits ranging from 0.10 to 0.91 visits per DM enrollee in all four chronic conditions. Most results were statistically significant at the 5% level, except for hypertension patients, where they were suggestive, though not significant. CONCLUSION: Disease management is effective in reducing potentially avoidable inpatient hospital stays and ER visits among patients with chronic illness. PMID- 17350087 TI - Ultrastructure and morphology of spermatozoa in Chinese sturgeon (Acipenser sinensis Gray 1835) using scanning and transmission electron microscopy. AB - The Chinese sturgeon (Acipenser sinensis Gray 1835) is an endangered anadromous sturgeon inhabiting the Yangtze River in China. In this study, the ultrastructure and morphology of spermatozoa was studied using transmission and scanning electron microscopy with a cryo-holder. The spermatozoon consisted of an elongated head with a distinct acrosome and nucleus region, a midpiece and a flagellum. The mean length of the head and midpiece, the flagellum and total length of spermatozoon were 4.48, 33.3 and 37.8 microm, respectively. The nucleus was an elongated trapezoid shape with anterior (acrosome) end narrower than the posterior. Granular material and an actin filament were observed within the anterior acrosome. Three to five endonuclear canals were present. The midpiece was eudipleural along its longitudinal axis. Compared to other sturgeon species, the data from the present study suggest a more recent evolutionary linkage between Chinese sturgeon and white sturgeon (Acipenser transmontanus Richardson 1836). PMID- 17350088 TI - Chemical activation of parthenogenetic and nuclear transfer porcine oocytes using ionomycin and strontium chloride. AB - Effective protocols for oocyte activation are crucial for study of parthenogenetic development and to produce nuclear transfer reconstructed embryos. This study investigated the use of ionomycin (ION) and strontium chloride (Sr(2+)) in the activation of parthenogenetic and nuclear transfer porcine oocytes. In-vitro-matured oocytes with a polar body were treated with varying concentrations of ION, Sr(2+) or its combinations, and then fixed or cultured to assess activation and development rates, respectively. Ionomycin concentrations of 10 and 15 microM resulted in more frequent oocyte activation and the 15 microM in advanced development compared to 5 microM (71.8 and 70%vs. 47.5%; P=0.04, and 43.7%vs. 19.3%; P=0.008, respectively). Oocytes treated with 10, 20 or 30 mM of Sr(2+) for 2 or 4h displayed a pronuclear formation rate ranging from 46.7 to 70%. When employed after a 5 min treatment with 10 or 15 microM ION, exposure to 10 mM Sr(2+) for 4 h resulted in higher pronuclear formation than did the 20 mM concentration (82 and 88.6%vs. 63.3 and 73.2%; P=0.03). Nuclear transfer reconstructed oocytes treated with 15 microM/5 min ION followed by 10 mM/4 h Sr(2+) resulted in a higher development to blastocyst stage compared to those treated with 15 microM ION alone (17.7 vs. 11.3%; P=0.06). In conclusion, we inferred that the inclusion of Sr(2+) in the activation protocol can benefit the development of nuclear transfer reconstructed porcine oocytes. PMID- 17350089 TI - Effects of trabecular calcium phosphate scaffolds on stress signaling in osteoblast precursor cells. AB - The objective of this research was to investigate stress-signaling patterns in response to two-dimensional (2-D) and three-dimensional (3-D) calcium phosphate (CP) materials using human embryonic palatal mesenchyme cells (HEPM, CRL-1486, ATCC, Manassas, VA), an osteoblast precursor cell line. Control discs and scaffolds were fabricated from hydroxyapatite and beta tri-CP ceramics. Phospho specific antibody cell-based ELISA technique was utilized on members of the mitogen-activated protein kinase cascade including; the extracellular signal regulated kinases (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and the anti apoptosis mediator protein kinase B (AKT). Quantification of these signals was evaluated during the early attachment phase of osteoblast precursor cells. In this study, it was observed that 3-D CP scaffolds significantly activated the stress mediators p38 and JNK but not ERK1/2. This signal trend was matched with an up-regulation in AKT, suggesting the ability of cells to manage high stress signals in response to 3-D CP architecture and that 3-D CP scaffolds are necessary for studies simulating a natural trabecular bone organization. The absence of these signals in 2-D CP surfaces indicated the importance of local architecture conditions on cell stress response. It was concluded from this study that osteoblast precursor cells cultured in 3-D CP scaffolds experience greater stress-signaling patterns when compared to 2-D CP surfaces. PMID- 17350090 TI - Bovine placental steroid sulphatase: molecular cloning and expression pattern in placentomes during gestation and at parturition. AB - Apart from during the prepartal period, the main oestrogen produced by the bovine trophoblast is oestrone sulphate (E1S) which does not bind to nuclear oestrogen receptors (ER). High steroid sulphatase (StS) activities previously detected in the maternal part of bovine placentomes (caruncles) suggest the local activation of E1S ("sulphatase pathway"). Consequently, the expression pattern of StS in bovine placentomes was investigated by immunohistochemistry using an antiserum against human placental StS. Cross-reactivity for bovine StS was confirmed by Western blot yielding a single band of 62 kDa in both bovine and human placenta. Immunostaining for StS was detected in caruncular epithelial cells (CEC), which was clearly related to gestational age. In animals pregnant between 100 and 284 days (n=17), signals were restricted to CEC adjacent to the chorionic plate and basal primary and secondary chorionic villi. After the onset of prepartal luteolysis (days 273-282; n=3) and during active labour (n=5) overall staining intensity had increased substantially and signals occurred ubiquitously in the flattened and partially dismantled caruncular epithelium. A 2204 bp full-length mRNA transcript of the bovine StS exhibiting 74% and 77% sequence identity to human StS on the mRNA and protein levels, respectively, was cloned by RACE-PCR. Real-time RT-PCR detected a 2.5-fold increase of StS-mRNA in prepartal placentomes, which, however, was not statistically significant. The co localisation of ERalpha and StS in CEC is consistent with a role of placental oestrogens as regulators of caruncular growth and differentiation, and the up regulation of carunclar StS may be involved in the marked prepartal increase of free oestrogens. PMID- 17350091 TI - A commentary on gestational programming and functions of HLA-G in pregnancy. AB - HLA-G is an HLA class Ib gene that is highly expressed in human trophoblast cells. The single HLA-G mRNA is alternatively spliced to generate at least seven transcripts, three of which encode soluble isoforms. Many studies have shown that high levels of soluble antigens are associated with successful implantation and graft acceptance. To study expression, regulation and functions of two of the soluble isoforms, HLA-G5 and HLA-G6, we generated recombinant proteins in eukaryotic cells and developed monoclonal antibodies specific for each of the two proteins. In addition, we investigated the olive baboon Paan-AG gene as a potential functional correlate of HLA-G. Here, we present summaries of the studies that have been conducted in our laboratory using these tools and discuss the results within the context of the research on this topic that is ongoing in ours and other laboratories worldwide. Collectively, the data indicate that soluble HLA-G is a critical contributor to immune privilege in pregnancy and imply that this placenta-derived substance may impact other pathways leading to successful reproduction. PMID- 17350092 TI - Hofbauer cells in early human placenta: possible implications in vasculogenesis and angiogenesis. AB - The stroma of the placental villi contain numerous macrophages, so-called Hofbauer cells which are of mesenchymal origin and are thought to function in many processes. Although there are many studies concerning placental vasculogenesis and angiogenesis, there has been a lack of evidence on the possible roles of Hofbauer cells in these processes. In this study we hypothesized that Hofbauer cell locations and numbers might be correlated with the vascular structures within the placental villi core and therefore may be implicated to play roles in placental vasculogenesis and angiogenesis. Placental tissues were obtained from normal first-trimester pregnancies. Tissues were prepared for light microscopic investigations. Double immunohistochemistry staining with CD31/PECAM1 and CD68 was applied to placental tissues. In placental villous core, majority of the Hofbauer cells were found to be either in close contact with angiogenic cell cords and primitive vascular tubes or located in between them. Moreover, the number of Hofbauer cells and vasculogenic structures were found to be significantly correlated. The findings of this study suggest for the first time that Hofbauer cells might be involved in the processes of vasculogenesis and angiogenesis in the placenta. PMID- 17350093 TI - Expression of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) genes in blasts of infant acute lymphoblastic leukemia with organ involvement. AB - The mRNA contents of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 in leukemia cells from 33 infants with acute lymphoblastic leukemia (ALL) were quantified at initial presentation, and the correlation between their expression and patient clinical characteristics was examined. The mRNA contents of MMP-2 and MMP-9 were not associated with any patient characteristics. Positive correlation was found between hepatosplenomegaly and the MMP-2/TIMP-1 and MMP-2/TIMP-2 ratios (p=0.005 and 0.009) and between CNS involvement and the MMP-2/TIMP-2 ratio (p=0.012). The results suggest that MMP/TIMP balance is closely related to the infiltration of leukemia cells into extramedullary organs. PMID- 17350095 TI - PTSD and stress sensitisation: a tale of brain and body Part 2: animal models. AB - Animal models that are characterised by long-lasting conditioned fear responses as well as generalised behavioural sensitisation to novel stimuli following short lasting but intense stress have a phenomenology that resembles that of PTSD in humans. These models include brief sessions of shocks, social confrontations, and a short sequence of different stressors. Subgroups of animals with different behavioural traits or coping styles during stress exposure show a different degree or pattern of long-term sensitisation. Weeks to months after the trauma, treated animals on average also show a sensitisation to novel stressful stimuli of neuroendocrine, cardiovascular and gastrointestinal motility responses as well as altered pain sensitivity and immune function. Functional neuroanatomical and pharmacological studies in these animal models have provided evidence for involvement of amygdala and medial prefrontal cortex, and of brain stem areas regulating neuroendocrine and autonomic function and pain processing. They have also generated a number of neurotransmitter and neuropeptide targets that could provide novel avenues for treatment in PTSD. PMID- 17350094 TI - The plasmid replicon of Epstein-Barr virus: mechanistic insights into efficient, licensed, extrachromosomal replication in human cells. AB - The genome of Epstein-Barr Virus (EBV) and plasmid derivatives of it are among the most efficient extrachromosomal replicons in mammalian cells. The latent origin of plasmid replication (oriP), when supplied with the viral Epstein-Barr Nuclear Antigen 1 (EBNA1) in trans, provides efficient duplication, partitioning and maintenance of plasmids bearing it. In this review, we detail what is known about the viral cis and trans elements required for plasmid replication. In addition, we describe how the cellular factors that EBV usurps are used to complement the functions of the viral constituents. Finally, we propose a model for the sequential assembly of an EBNA1-dependent origin of DNA synthesis into a pre-Replicative Complex (pre-RC), which functions by making use only of cellular enzymatic activities to carry out the replication of the viral plasmid. PMID- 17350096 TI - Comments on "effect of soil properties on arsenic fractionation and bioaccessibility in cattle and sheep dipping vat sites" by D. Sarkar et al. (2007) Environment International 33 (2007) 164-169. PMID- 17350097 TI - A flexible matrix algebra framework for the multimedia multipathway modeling of emission to impacts. AB - When assessing human health or ecosystem impacts of chemicals several calculation steps need to be addressed. Matrix algebra solving techniques are a useful approach to structure and solve the system of mass balance equations assessing chemical fate in environmental multimedia models. We suggest expanding this matrix approach towards a framework which includes the exposure, effect, and damage assessment for human health and ecosystems, also applicable to spatial modeling. Special emphasis is laid upon interpretation of the physical meaning of different elements within the matrices. The proposed framework provides several advantages such as simplified updating or extending of models to new impact pathways, possibility of covering various models within the same framework and transparency. Interpretation of intermediate and final results is facilitated, e.g., allowing for direct identification of dominating exposure pathways. Model comparability and evaluation is well supported, as the four matrices contain all intermediate results in a clear and interpretable way, independent from parameters, such as amount and place of emission. Multidisciplinary work is strongly facilitated enabling the linkage of different models from various disciplines together, since each of its modules defines a clear interface of intermediate results. This framework was reviewed by an independent expert panel within a UNEP/SETAC workshop, and adopted as starting-point for new advances in modeling environmental toxic releases within the UNEP/SETAC Life Cycle Initiative. PMID- 17350098 TI - Multicomponent T2 analysis of dithiocarbamate-mediated peripheral nerve demyelination. AB - Standard light microscope histological evaluation of peripheral nerve lesions has been used routinely to assess peripheral nerve demyelination; however, the development of magnetic resonance (MR) methodology for assessing peripheral nerve may provide complementary information, with less expense and in less time than nerve histology methods. In this study, the utility of multicomponent NMR T(2) relaxation analysis for assessing myelin injury in toxicology studies was examined using two dithiocarbamates, N,N-diethyldithiocarbamate (DEDC) and pyrrolidine dithiocarbamate (PDTC), known to produce myelin injury and elevate copper in the nervous system. T(2) analysis was used in conjunction with standard histological methods to assess myelin injury and determine if dithiocarbamate mediated copper accumulation in peripheral nerve was associated with more severe myelin lesions. Male Sprague-Dawley rats were administered i.p. DEDC for 8 weeks and maintained on either a diet containing normal (13 ppm) or elevated (200 ppm) copper. Another group of male Sprague-Dawley rats was administered oral PDTC and a 200 ppm copper diet, with controls given only the 200 ppm copper diet, for 47 weeks. Following exposures, the morphology of sciatic nerve was evaluated using light microscopy and multicomponent T(2) analysis of excised fixed nerves; and copper levels in sciatic nerve were determined using ICP-AES. Light microscopy demonstrated the presence of a primary myelinopathy in dithiocarbamate-exposed rats characterized by intramyelinic edema, demyelination, and secondary axonal degeneration. Both the nerve copper level and number of degenerated axons, as ascertained by ICP-AES and microscopy, respectively, were augmented by dietary copper supplementation in conjunction with administration of DEDC or PDTC. T(2) analysis revealed a decreased contribution from the shortest T(2) component in multicomponent T(2) spectra obtained from animals administered DEDC or PDTC, consistent with decreased myelin content; and the decrease of the myelin water component was inversely correlated to the levels of nerve copper and myelin lesion counts. Also, the T(2) analysis showed reduced variability compared to histological assessment. These studies support multicomponent T(2) analysis as a complementary method to light microscopic evaluations that may also be applicable to in vivo assessments. PMID- 17350100 TI - Time course of biochemical and behavioural effects of a single high dose of chlorpyrifos. AB - The purpose the present study was to determine if tolerance is developed to all behavioural effects produced by a single high dose of chlorpyrifos (CPF). For this, the study was divided in two phases; in the first phase, we studied the time course of the effects produced by treatment with a high dose of CPF (250 mg/kg s.c.) on rat locomotor activity and anxiety behaviours recorded on an open field, as well as on AChE inhibition. Results showed that CPF produced a maximum inhibition of AChE (72% of inhibition) 2 days after its administration, exhibiting a partial recovery of its activity by day 30 (55% of inhibition). On locomotor activity CPF produced a biphasic effect; a reduction only on day 2, and an increase on day 30. An anxiolytic-like effect was only observed within 2 and 5 days after CPF treatment. These results indicate that the tolerance has been developed to the behavioural effects produced by s.c. administration of CPF, but with a different time course. In the second phase, since disturbances in cholinergic system might trigger dopaminergic dysfunctions, we tested the locomotor activity following challenge with amphetamine (1mg/kg i.p.) at 11 and 30 days after CPF treatment. Data obtained showed that amphetamine produced an increase in total distances and rearing in vehicle and CPF groups on days 11 and 30. However, CPF group exhibited lower increase relative to vehicle group in both days. This effect is independent of the percentage of AChE inhibition and therefore, of change in the cholinergic system. Data are discussed under the light of the adaptative mechanisms underlying the recovery of the cholinergic overstimulation after s.c. exposure to high doses of CPF. PMID- 17350099 TI - Can endocrine disruptors influence neuroplasticity in the aging brain? AB - Only within the last two decades has the adult mammalian brain been recognized for its ability to generate new nerve cells and other neural structures and in essence to rewire itself. Although hippocampal structures have received the greatest scrutiny, other sites, including the cerebral cortex, also display this potential. Such processes remain active in the aging brain, although to a lesser degree. Two of the factors known to induce neurogenesis are environmental enrichment and physical activity. Gonadal hormones, however, also play crucial roles. Androgens and estrogens are both required for the preservation of cognitive function during aging and apparently help counteract the risk of Alzheimer's disease. One overlooked threat to hormonal adequacy that requires close examination is the abundance of environmental endocrine-disrupting chemicals that interfere with gonadal function. They come in the form of estrogenic mimics, androgen mimics, anti-estrogens, anti-androgens, and in a variety of other guises. Because our brains are in continuous transition throughout the lifespan, responding both to environmental circumstances and to changing levels of gonadal steroids, endocrine-disrupting chemicals possess the potential to impair neurogenesis, and represent a hazard for the preservation of cognitive function during the later stages of the life cycle. PMID- 17350101 TI - The benefits and drawbacks of nicotine exposure in the cortex and hippocampus of old rats. AB - Nicotine is the main alkaloid of tobacco and possesses well-established stimulant effects. Previous reports show that nicotine at low doses improves memory functions, while high doses impair memory. This study aims to analyze the effects of nicotine (NIC) on inhibitory avoidance task and on DNA damage, reactive oxygen species (ROS) concentration, total antioxidant capacity, and lipid peroxidation in cortex and hippocampus of old rats. Male Wistar rats of 24-26 months old (620 700g) were exposed i.p. to two doses (0.3 and 1mg/kg) of NIC daily during 9 days. The treatment NIC 0.3 enhanced long-term memory (p<0.05), whereas NIC 1 improved both short and long-term memories (p<0.05). DNA damage was observed only in hippocampus (p<0.05) after NIC 1 exposure. A similar result was obtained for ROS: higher levels were detected at NIC 1 treatment in hippocampus (p<0.05). No alterations in the total antioxidant capacity were verified after NIC exposure (0.3 and 1mg/kg) in both tissues (p>0.05). Finally, evidence of oxidative damage was observed in terms of lipid peroxides levels, being higher at NIC 1 in hippocampus (p<0.05). Overall the results indicate that deleterious effects paralleled the improved short and long-term memories at the highest NIC dose, since augmented DNA damage, ROS concentration and lipid peroxides levels were registered. PMID- 17350102 TI - Catalytic sterilization of Escherichia coli K 12 on Ag/Al2O3 surface. AB - Bactericidal action of Al(2)O(3), Ag/Al(2)O(3) and AgCl/Al(2)O(3) on pure culture of Escherichia coli K 12 was studied. Ag/Al(2)O(3) and AgCl/Al(2)O(3) demonstrated a stronger bactericidal activity than Al(2)O(3). The colony-forming ability of E. coli was completely lost in 0.5 min on both of Ag/Al(2)O(3) and AgCl/Al(2)O(3) at room temperature in air. The configuration of the bacteria on the catalyst surface was observed using scanning electron microscopy (SEM). Reactive oxygen species (ROS) play an important role in the expression of the bactericidal activity on the surface of catalysts by assay with O(2)/N(2) bubbling and scavenger for ROS. Furthermore, the formation of CO(2) as an oxidation product could be detected by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and be deduced by total carbon analysis. These results strongly support that the bactericidal process on the surface of Ag/Al(2)O(3) and AgCl/Al(2)O(3) was caused by the catalytic oxidation. PMID- 17350104 TI - Comment on "Vibrio vulnificus and V. parahaemolyticus necrotising fasciitis in fishermen visiting an estuarine tropical northern Australia location". PMID- 17350106 TI - A method for microbial cell surface fingerprinting based on surface plasmon resonance. AB - A method for microbial cell surface fingerprinting using surface plasmon resonance (SPR) is suggested. Four different Escherichia coli mutants have been used as model cells. Cell surface fingerprints were generated by registration of the interaction between the cell mutants and four different surfaces, with different physical and chemical properties, when a cell suspension was flown over the surface. Significant differences in fingerprint pattern between some of the mutants were observed. At the same time, the physical properties of the cell surfaces were determined using microelectrophoresis, contact angle measurements and aqueous two-phase partitioning and compared to the SPR fingerprints. The generated cell surface fingerprints and the physical property data were evaluated with multivariate data analysis that showed that the cells were separated into individual groups in a similar way using principal component analysis plots (PCA). PMID- 17350105 TI - Impact of thrombocytopenia on outcome of patients admitted to ICU for severe community-acquired pneumonia. AB - OBJECTIVE: To evaluate the prevalence and the prognostic value of thrombocytopenia in patients admitted to ICU for severe community-acquired pneumonia. METHODS: Multicentre observational study was conducted in 7 ICUs in the north of France over a 19-year period (1987-2005). The primary outcome measure was the ICU mortality. RESULTS: Eight hundred and twenty-two patients were studied. A platelet count < 150x10(9)/L was observed at ICU admission in 202 (25%) patients. Admission platelet count was between 101 and 149x10(9)/L, 51 and 100x10(9)/L, 21 and 50x10(9)/L, and < or = 20x10(9)/L in 100, 61, 32 and 9 patients, respectively. ICU mortality rate was 35.4%. Classifying patients into 3 categories with the following cut-offs of platelet count, > or = 150x10(9)/L, 51 149x10(9)/L, and < or = 50x10(9)/L, we observed a significant increase in ICU mortality rates which were 30.8% in the first group, 44.1% in the second group and 70.7% in the last one (p<0.0001). In multivariate analysis, thrombocytopenia < or = 50x10(9)/L appeared as an independent predictor of mortality (AOR=4.386). CONCLUSIONS: In patients admitted to ICU for severe community-acquired pneumonia, thrombocytopenia has a high prevalence and influences the outcome. PMID- 17350107 TI - IgG autoantibodies directed against desmoglein 3 cause dissociation of keratinocytes in canine pemphigus vulgaris and paraneoplastic pemphigus. AB - Pemphigus is a group of autoimmune blistering diseases of the skin and mucous membranes. In human patients with pemphigus vulgaris (PV) and paraneoplastic pemphigus (PNP), IgG autoantibodies against desmoglein (Dsg) 3 and Dsg1 play pathogenic roles in blister formation. In contrast, the target for IgG autoantibodies that induce keratinocyte dissociation has not been elucidated in canine pemphigus. The aim of the present study was to determine whether anti-Dsg IgG autoantibodies are present and disrupt the cell-cell adhesion of keratinocytes in canine PV and PNP. The extracellular domains of canine Dsg3 were recognized by IgG in 3/5 (60%) canine PV sera tested. IgG against the extracellular domains of canine Dsg1 was detected exclusively in two dogs that had PV with the mucocutaneous phenotype. In addition, anti-Dsg3 IgG was identified in canine PNP serum. Furthermore, incubation of normal human keratinocytes (NHK) with mucocutaneous canine PV serum and canine PNP serum resulted in dissociation of the NHK sheets, whereas the removal of anti-Dsg3 IgG from these canine sera blocked this dissociation. The present study indicates for the first time that circulating anti-Dsg3 IgG antibodies capable of dissociating keratinocytes are present in dogs with PV and PNP. PMID- 17350108 TI - Maternal social stress during pregnancy alters immune function and immune cell numbers in adult male Long-Evans rat offspring during stressful life-events. AB - The impact of social confrontations on distribution and function of blood immune cells in adult male rat offspring from stressed and non-stressed pregnancies was studied. Repeated 2 h resident-intruder confrontations were performed on ten consecutive days using a protective cage. Prenatally stressed intruder males (PSI) had a generally lower number of neutrophiles, monocytes, T and NK cells and reduced lymphocyte proliferation in whole blood cultures than prenatally non stressed control intruders (PCI). Differences also existed in the temporal dynamics of immunological changes. On confrontation day 1, stress-induced reductions in lymphocyte and monocyte numbers but increased granulocyte counts were observed in both groups. However, only PCI showed a partial recovery of T cell and monocyte numbers on confrontation day 10 and a full restoration in all immune cell numbers 5 days post-confrontation. Thus, the immunological response to a psychosocial stressor in adult rats can be modified by the mothers' exposure to stress during pregnancy. PMID- 17350109 TI - Phosphorylation-independent attenuation of GPCR signalling. AB - The uncoupling of G-protein-coupled receptors (GPCRs) from their cognate heterotrimeric G proteins provides an essential physiological 'feedback' mechanism that protects against both acute and chronic overstimulation of receptors. The primary mechanism by which GPCR activity is regulated is the feedback phosphorylation of activated GPCRs by kinases that are dependent on second messengers, GPCR kinases (GRKs) and arrestins. It has recently become apparent, however, that GRK2-mediated regulation of GPCR responsiveness also involves a phosphorylation-independent component that requires both heterotrimeric G-protein alpha-subunit interactions and GPCR binding. Moreover, in addition to GRK2, a growing number of GPCR-interacting proteins might contribute to the phosphorylation-independent G-protein uncoupling of GPCRs. Here, new information about the mechanisms underlying this phosphorylation independent regulation of receptor and G-protein coupling is reviewed. PMID- 17350110 TI - Off-target effects associated with long dsRNAs in Drosophila RNAi screens. AB - Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29bp) in mammalian cells has existed for several years. Two recent articles demonstrate that short sequences within long double-stranded (ds)RNAs frequently cause undesirable OTEs in cultured Drosophila cells. These results reveal the potential for high false-positive rates in RNA interference (RNAi) screens using long dsRNAs and highlight the need for screening with multiple, non-overlapping long dsRNAs or siRNAs. Discovering multiple potent siRNAs with minimal off-target profiles for each target transcript will be invaluable for genome-based studies of gene function and for personalized RNAi therapeutics. PMID- 17350111 TI - The emergence of adamantane resistance in influenza A(H1) viruses in Australia and regionally in 2006. AB - The adamantanes (amantadine and rimantadine) were the first antivirals licensed for use against influenza A viruses and have been used in some countries to control seasonal influenza. While increasing resistance of A(H3) viruses to this class of drug has been reported in recent years, only low levels of resistance were seen with A(H1) viruses until the 2005-2006 influenza season in the USA. In this study we analysed 101 human influenza A viruses isolated in 2006 that were referred to the WHO Collaborating Centre for Reference and Research in Melbourne, from Australia and the surrounding regions, for evidence of resistance to adamantanes. We found that whereas previously A(H1) resistant viruses were rare, 21.8% of the 2006 viruses had a resistant genotype. By comparison, 58.6% of influenza A(H3) viruses isolated in 2006 that were tested at the Centre, had a resistant genotype. PMID- 17350112 TI - Electrical stimulation of the ventral tegmental area exerts opposite effects on male rat sexual behaviour expression depending on the stimulated sub region. AB - The effects of electrical stimulation of the ventral tegmental area (VTA) on male rat sexual behaviour were studied. Stimulation of dorsal VTA facilitated copulation of sexually experienced animals; while ventral VTA stimulation inhibited sexual behaviour. In sexually exhausted rats, stimulation at either region lacked of an effect. It is concluded that different loci within the VTA exert opposite influences on male sexual behaviour expression and that copulation to satiation modifies this VTA control. PMID- 17350113 TI - To move or not: previous experience in a runway avoidance task determines the appearance of hippocampal Type 2 sensory processing theta. AB - Rats in a runway avoidance task responded to a test shock probe with a period of immobility lasting from 2 to 6s. The shock avoidance-trained group displayed hippocampal theta during the immobility response. The inescapable shock group, in contrast, displayed large amplitude irregular activity (LIA). Following reversal training to escapable shock, all shock avoidance-trained rats responded with LIA and inescapable shock trained rats, reversed to shock avoidance, displayed theta. PMID- 17350114 TI - Atropine-induced, state-dependent learning for spatial information, but not for visual cues. AB - This study investigates state-dependent learning employing atropine. The reaction of rats to (1) the presentation of novel stimuli, (2) habituation to intermittent presentations of the same stimulus at the same local, (3) spatial change at the site of stimulus presentation, and (4) a visual stimulus change, was investigated in the straight alleyway test, controlling for the possible development of behavioral and/or pharmacological tolerance. Our findings reveal that rats habituated to stimulus presentation at a specific location, when under an atropine effect, do react to stimulus presentation at another location, or to a different stimulus, when under an atropine effect, indicating that this drug does not interfere with the acquisition of spatial or visual information. Differently, however, rats habituated to stimulus presentation at a specific location in the absence of an atropine effect are unable to react to spatial change when under the atropine effect, but do react to a visual stimulus change. This suggests that atropine interferes either with the retrieval of previously acquired spatial information or with the comparison of previously acquired spatial information with current information, but does not interfere with visual recognition. These findings reveal that atropine interferes with the use of spatial information acquired in the absence of a drug effect. PMID- 17350115 TI - Interaction of AT1 receptors and V1a receptors-mediated effects in the central cardiovascular control during the post-infarct state. AB - Experimental objectives. Because myocardial infarct is associated with overactivation of brain angiotensin II (ANG II) and vasopressin (AVP) V1a receptors we decided to determine whether AT1 and V1a receptors-mediated effects of ANG II and AVP interact in central cardiovascular control during the post infarct state. Four groups of infarcted and four groups of sham-operated conscious rats entered the study. Results. In the infarcted rats cerebroventricular infusion of AT1 (AT1ANT, losartan) and V1a antagonist {V1aANT,d(CH(2))(5)[Tyr(Me)(2)Ala-NH(2)(9)]VP} and combined infusion of both these compounds performed 4 weeks after induction of the infarct significantly and comparably reduced mean arterial blood pressure (MABP) in comparison to control experiments (artificial cerebrospinal fluid infusion). In the sham rats MABP was not affected by any of the infusions. In control experiments MABP and HR responses to an alarming air jet stress were significantly higher in the infarcted than in the sham rats. Both responses were normalized with the same effectiveness by administration of AT1ANT, V1aANT and AT1ANT+V1aANT. In the sham rats administration of these compounds did not affect MABP and HR responses to stress. CONCLUSION: The results provide evidence for interaction of AT1 and V1a receptors-mediated effects of ANG II and AVP in the central cardiovascular control during the post-infarct state. PMID- 17350116 TI - Angiotensin-(3-7) pressor effect at the rostral ventrolateral medulla. AB - Ang-(3-7) is a fragment of the renin-angiotensin system that can be derived both from Ang II or Ang-(1-7). In the present study we determined the cardiovascular effects produced by angiotensin-(3-7) [Ang-(3-7)] microinjection into the rostral ventrolateral medulla (RVLM), a key region for the control of sympathetic drive to the periphery. RVLM microinjection of Ang-(3-7) (20, 40 or 80 ng) in male Wistar rats anesthetized with urethane produced significant increases in MAP (19+/-3.8 mm Hg, n=5; 16+/-1.6 mm Hg, n=15 and 11+/-1.2 mm Hg, n=4, respectively) as compared to saline (4+/-0.7 mm Hg, n=6). These alterations were similar to that induced by Ang-(1-7) (14+/-1.3 mm Hg, 40 ng; n=12) and Ang II (17+/-2.3 mm Hg, 40 ng; n=7). Microinjection of losartan (AT(1) receptor antagonist, 100 pmol) or A779 (selective Mas receptor antagonist, 100 pmol) did not alter the pressor effect caused by Ang-(3-7). Microinjection of an Ang-(3-7) analogue, d-Ala(7)-Ang (3-7) (100 pmol), completely abolished the pressor effect caused by Ang-(3-7). These results suggest that Ang-(3-7) may be an additional peptide of the RAS to act as neuromodulator, at least at the RVLM. Further, the Ang-(3-7) pressor effect is not mediated by the interaction with AT(1) or the Ang-(1-7), Mas, receptors. PMID- 17350117 TI - In vivo footprinting analysis of the Glypican 3 (GPC3) promoter region in neuroblastoma cells. AB - Glypican 3 (GPC3) is an X-linked gene that has its peak expression during development and is down-regulated in all studied tissues after birth. We have shown that GPC3 was expressed in neuroblastoma and Wilms' tumor. To understand the mechanisms regulating the transcription of this gene in neuroblastoma cells, we have focused our study on the identification of putative transcription factors binding the promoter. In this report we performed in vivo dimethylsulfate, UV type C irradiation and DNaseI footprinting analyses coupled with ligation mediated PCR on nearly 1000 bp of promoter in two neuroblastoma cell lines, SJNB 7 (expressing GPC3) and SK-N-FI (not expressing GPC3). Nucleosome signature footprints were observed in the most distal part of the studied region in both cell lines. We detected eight large differentially protected regions, suggesting the presence of binding proteins in both cell lines but more DNA-protein interactions in GPC3-expressing cells. Sp1 was previously shown to be able to bind some of these regions. Here by combining electromobility shift assays and chromatin immunoprecipitations we showed that the transcription factor NFY was part of the DNA-protein complex found in footprinted regions upstream of the described minimal promoter. These studies performed on chromatin in situ suggest that NFY and yet unknown cell type-specific factors may play an important role in the regulation of GPC3. PMID- 17350118 TI - Acute coronary syndrome caused by left main coronary artery plaque rupture and thrombosis - resolution after pharmacological treatment. AB - The article presents a case of a 68-year old male admitted to coronary care unit because of acute coronary syndrome without ST segment elevation. In coronary angiography a lesion in the left main coronary artery (LMCA) is found. Intravascular ultrasound (IVUS) examination confirms the diagnosis of the ruptured plaque with the presence of thrombus. Because of the well preserved lumen area a decision to continue intensive pharmacotherapy is made. Follow-up angiography and IVUS show a complete resolution of thrombus. The article discusses different management strategies in patients with confirmed ruptured plaque in LMCA. PMID- 17350119 TI - Perforation of the right ventricular free wall by an ICD lead in a patient with isolated noncompaction of the ventricular myocardium. AB - A 74-year-old patient with isolated noncompaction of the ventricular myocardium (INVM) underwent implantable cardioverter defibrillator (ICD) implantation because of sustained ventricular tachycardia. The post operative course was complicated by perforation of the right ventricular free wall by the ICD lead. The type of the active fixation transvenous ICD lead and the type of background cardiac disease are thought to be major risk factors for perforation. PMID- 17350121 TI - Diagnosis contribution of IVUS in embolic myocardial infarction. PMID- 17350122 TI - Radiofrequency pulmonary valvulotomy and valvuloplasty using transductal guidewire rail and translevofemoral venous slide: an unhackneyed solution to a newborn with pulmonary atresia, intact ventricular septum, upstream patent ductus arteriosus, and sigmoid inferior vena cava. PMID- 17350123 TI - A method for comparison of growth media in objective identification of Penicillium based on multi-spectral imaging. AB - We consider the problems of using excessive growth media for identification and performing objective identification of fungi at the species level. We propose a method for choosing the subset of growth media, which provides the best discrimination between several fungal species. Furthermore, we propose the use of multi-spectral imaging as a means of objective identification. Three species of the fungal genus Penicillium are subject to classification. To obtain an objective classification we use multi-spectral images. Previously, RGB images have proven useful for the purpose. We use multi-spectral bands as they provide additional information about the chemistry of the fungal colonies. In this study three media [Czapek yeast extract agar (CYA), oatmeal agar (OAT), and yeast extract sucrose agar (YES)] have been compared on their ability to discriminate between the three species. We propose a statistical method to test which medium or combination of media gives the best discrimination. Statistical tests indicate that YES combined with CYA is the best choice of media in this case. However, for the objective identification one medium is sufficient to discriminate between the species. Statistical tests show that there are significant differences between the species on all individual media, and that these differences are largest on YES. The objective identification has been performed solely by means of digital image analysis. The features obtained from the image analysis merely correspond to macro-morphological features. The species have been classified using only 3-4 of the spectral bands with a 100% correct classification rate using both leave one-out cross-validation and test set validation. PMID- 17350124 TI - On the dose to a moving target while employing different IMRT delivery mechanisms. AB - BACKGROUND AND PURPOSES: To compare the temporal uniformity in dose delivered to a moving target for various intensity modulation radiotherapy (IMRT) modalities: solid intensity modulator (SIM), segmented multi-leaf collimator (SMLC), and dynamic multi-leaf collimator (DMLC). MATERIALS AND METHODS: Two separate four dimensional computed tomography data sets were obtained. Tumor motion kernels and motion envelopes were determined from composite positions of the tumor in various phases of the breathing cycle. Treatment plans were created for an unmodulated open field, SIM, SMLC, and DMLC. The motion envelope was treated as a static target volume. A robotic apparatus equipped with a diode array simulated the tumor motion in the plane of the beam's eye view (BEV). Radiation was delivered to the moving target over ten trials for each modality. The average coefficient of variation (CV) was determined for each beam angle. RESULTS: The CV ranged from 0.09% to 0.15%, 0.23% to 3.14%, 1.14% to 5.51%, and 3.83% to 8.25% for the unmodulated open field, SIM, SMLC, and DMLC modalities, respectively. With gating, the CV was 0.23% to 2.31%, 0.31% to 2.97%, and 0.7% to 4.67% for SIM, SMLC, and DMLC, respectively. CONCLUSION: SIM consistently provided the most temporally uniform dose to the moving target while DMLC provided the least. The SMLC and DMLC CV improved with gated delivery. PMID- 17350125 TI - Subjective and physiological responses to emotion-eliciting pictures in male schizophrenic patients. AB - Several studies have shown that schizophrenic patients have difficulties in their ability to recognize emotional facial expressions, whereas other research indicated that they subjectively report the same emotional experience as healthy controls. The purpose of this study was to investigate whether the physiological responses that accompany emotions differ between schizophrenic patients and controls, which would suggest a different basic emotional processing mechanism in these patients. We presented 40 emotion-eliciting pictures to male patients (n=26) and controls (n=21), while measuring heart rate (HR), breathing rate (BR), skin conductance response (SCR) and systolic blood pressure (SBP). Each subject rated each picture for its degree of valence and arousal. Mixed-effects regression models were used to investigate the relationships between the subjective ratings and the physiological responses. In both groups, BR and SCR increased with increasing arousal ratings, suggesting sympathetic activation. The SBP of both groups increased with increases in both the valence and the arousal ratings. However, whereas the patients' HR first decreased with decreasing pleasure ratings and subsequently increased with higher arousal and valence ratings, the HR in the control group was influenced by a complex interaction between valence and arousal ratings. Thus, the schizophrenic patients showed similar relationships between subjective ratings and SCR, BR, and SBP, but a different relationship between subjective ratings and HR compared with the healthy controls. PMID- 17350126 TI - Sensorimotor gating and anxiety: prepulse inhibition following acute exercise. AB - This investigation examined whether gating related deficits among individuals with high trait anxiety could be moderated by an acute bout of exercise. Low (LA) and high (HA) trait anxious participants engaged in either a quiet rest or an exercise session on separate occasions. Replicating previous findings, HA participants exhibited significantly reduced PPI at lead intervals of 30 and 60 ms relative to LA controls. HA and LA participants were also found to occasion similar PPI following exercise relative to quiet rest. This finding was found to be independent of the order in which quiet rest or exercise occurred, and was not a function of differences in raw startle blink amplitude between sessions. The current results highlight the potential for PPI to index the potential anxiolytic effects of an acute exercise bout. PMID- 17350127 TI - New approach to the fungal decontamination of wheat used for wheat sprouts: effects of aminolevulinic acid. AB - Nowadays, there is a growing interest in natural, minimally processed, nutritional and healthy foods. Sprouted seeds can be offered as natural nutritive products. Regrettably, existing seed decontamination technologies are limited and have specific disadvantages. 5-aminolevulinic acid (5-ALA) as a novel and effective tool for wheat decontamination from microfungi is proposed in this work. Inhibition of wheat with 5-ALA revealed a drastically suppressed development of microfungi. Studies of wheat germination characteristics showed that 5-ALA stimulates the growth of wheat seedlings and roots without impairing the vigor of germination and the viability of seeds. 5-ALA also induces either marginal or significant activities of antioxidant enzymes which can be associated with enhanced cellular capacity to detoxify reactive oxygen species. The results indicate that 5-ALA application may be an effective, environmentally friendly and inexpensive technology to be used in producing sprouts for human consumption. PMID- 17350128 TI - A comparison of single oxidants versus advanced oxidation processes as chlorine alternatives for wild blueberry processing (Vaccinium angustifolium). AB - Advanced oxidation processes and single chemical oxidants were evaluated for their antimicrobial efficacy against common spoilage bacteria isolated from lowbush blueberries. Predominant bacterial flora were identified using biochemical testing with the assessment of relative abundance using non-selective and differential media. Single chemical oxidants evaluated for postharvest processing of lowbush blueberries included 1% hydrogen peroxide, 100 ppm chlorine, and 1 ppm aqueous ozone while advanced oxidation processes (AOPs) included combinations of 1% hydrogen peroxide/UV, 100 ppm chlorine/UV, and 1 ppm ozone/1% hydrogen peroxide/UV. Enterobacter agglomerans and Pseudomonas fluorescens were found to comprise 90-95% of the bacterial flora on lowbush blueberries. Results of inoculation studies reveal significant log reductions (p< or 5) in populations of E. agglomerans and P. fluorescens on all samples receiving treatment with 1% hydrogen peroxide, 1% hydrogen peroxide/UV, 1 ppm ozone, or a combined ozone/hydrogen peroxide/UV treatment as compared to chlorine treatments and unwashed control berries. Although population reductions approached 2.5 log CFU/g, microbial reductions among these treatments were not found to be significantly different (p< or 5) from each other despite the synergistic potential that should result from AOPs; furthermore, as a single oxidant, UV inactivation of inoculated bacteria was minimal and did not prove effective as a non-aqueous bactericidal process for fresh pack blueberries. Overall, results indicate that hydrogen peroxide and ozone, as single chemical oxidants, are as effective as AOPs and could be considered as chlorine alternatives in improving the microbiological quality of lowbush blueberries. PMID- 17350129 TI - Real-time RT-PCR quantification of Kuruma shrimp transcripts: a comparison of relative and absolute quantification procedures. AB - Housekeeping genes are often used as references when quantifying the relative abundance of transcripts of interest, because it is assumed that they are stably expressed across tissues and developmental stages. Standard housekeeping genes are targeted particularly in organisms where there is no detailed information on gene expression profiles. Here, the validity of using the two widely accepted housekeeping genes, 18S rRNA and beta-actin, as reference genes to normalize real time RT-PCR gene expression data from the Kuruma shrimp, Marsupenaeus japonicus, was tested. Expression patterns of two target genes in a diverse sample set of embryonic, larval, post-larval and gonad mRNAs were quantified using relative and absolute real-time RT-PCR procedures. Comparison of these approaches revealed significant differences (P<0.0001) in transcript level profiles between the relative and absolute procedures for both target genes. When 18S rRNA was used as a reference, target gene expression was more similar to that of the absolute method than when beta-actin was used as a reference. Variability between the relative and absolute procedures occurred for a greater percentage of the embryonic stages compared to later developmental stages. This study indicates that the use of 18S rRNA and beta-actin for studying relative gene expression patterns in Kuruma shrimp embryonic, larval, post-larval and gonad samples will give significantly variable results, and illustrates the proposition that housekeeping genes are not necessarily appropriate references for real-time RT PCR data normalization. Until suitable reference genes are characterized, gene expression experiments using the studied Kuruma shrimp tissues of different morphological developmental stages should use absolute quantification procedures. PMID- 17350130 TI - Reverse genetics for peste-des-petits-ruminants virus (PPRV): promoter and protein specificities. AB - Peste-des-petits-ruminants virus (PPRV) (family Paramyxoviridae, genus Morbillivirus) causes an acute febrile illness in sheep and goats resulting in significant morbidity and mortality in infected herds. The paramyxoviruses all have negative sense, non-segmented RNA genomes and their host range and pathogenic determinants have been extensively studied using reverse genetics. This technology also enables a more rational approach to be taken with respect to vaccine design. In order to initiate this type of work for PPRV we constructed a PPRV minigenome and studied its expression in transfected cells. As for other morbilliviruses, the minimum requirements for minigenome rescue were shown to be the cis-acting elements of the genome (GP) and antigenome (AGP) promoters as well as the three trans-acting helper proteins N (nucleocapsid), P (phosphoprotein) and L (large polymerase). Homologous PPRV helper proteins were compared to their heterologous analogues from the closely related rinderpest virus (RPV) and heterologous minigenome rescue was found to be a much less efficient process. By engineering two GP/AGP chimeric minigenomes we also identified differences between the two viruses in the specific interactions between the promoters and the transcriptase/replicase complexes. The PPRV minigenome was also shown not to strictly comply with the "rule of six"in vitro. PMID- 17350131 TI - Synthesis and characterization of highly-magnetic biodegradable poly(d,l-lactide co-glycolide) nanospheres. AB - The objective of this study was to develop high magnetization, biodegradable/biocompatible polymer-coated magnetic nanospheres for biomedical applications. Magnetic spheres were prepared by a modified single oil-in-water emulsion-solvent evaporation method utilizing highly-concentrated hydrophobic magnetite and poly(d,l lactide-co-glycolide) (PLGA). Hydrophobic magnetite prepared using oleic acid exhibited high magnetite concentrations (84 wt.%) and good miscibility with biopolymer solvents to form a stable oily suspension. The oily suspension was then emulsified within an aqueous solution containing poly(vinyl alcohol). After rapid evaporation of the organic solvent, we obtained solid magnetic nanospheres. We characterized these spheres in terms of external morphology, microstructure, size and zeta potential, magnetite content and distribution within the nanospheres, and magnetic properties. The results showed good encapsulation where the magnetite distorted the smooth surface morphology only at the highest magnetite concentrations. The mean diameter was 360-370 nm with polydispersity indices of 0.12-0.20. We obtained high magnetite content (40 60%) and high magnetization (26-40 emu/g). The high magnetization properties were obtained while leaving sufficient polymer to retain drugs making these biodegradable spheres suitable as a potential platform for the design of magnetically-guided drug delivery and other in vivo biomagnetic applications. PMID- 17350132 TI - [Isokinetic trunk strength testing in chronic low back pain. The role of habituation and training to improve measures]. AB - Isokinetic dynamometers put subjects in very different conditions from natural movement. Familiarization with the isokinetic device may therefore explain better performance without showing any improvement in strength. OBJECTIVE: To determine the part of habituation and training in improved trunk isokinetic performance on isometric assessment after a back rehabilitation program for chronic low back pain. METHODS: A total of 26 patients with chronic low back pain consecutively admitted to the same rehabilitation department for a 4-week rehabilitation program underwent isometric assessment of the trunk flexors and extensors on the day of admission and 2 days and 21 days after admission. The maximal torque and total work were registered at 30 degrees , 90 degrees and 120 degrees/s. RESULTS: Values for all parameters, except flexor values at 30 degrees/s, were significantly improved between day 0 and day 2 after admission. Between day 2 and day 21 after admission, values for all parameters were improved significantly. Except for flexor values at 30 degrees/s, the parameter values at day 2 showed improvement ranging from 33% to 58% of the improvement seen at day 21. DISCUSSION: The improvement in parameter values found on isokinetic assessment two days after a one-day rehabilitation program for low back pain is probably explained by a habituation effect. We can expect that increase in the maximal torque and total work after 3 weeks of rehabilitation is, at least in part, the consequence of the strengthening program. CONCLUSION: We should interpret with caution the results of studies involving an isokinetic dynamometer to measure the strength of trunk muscles without a learning training. PMID- 17350133 TI - Using common clinical data improves the prediction of abnormal glucose tolerance by the new criteria of impaired fasting glucose: Tehran lipid and glucose study. AB - OBJECTIVE: To identify a subgroup of individuals with impaired fasting glucose (IFG) based on the new 2003 criteria that would most likely benefit from performance of oral glucose tolerance test. METHODS: A cross-sectional study was carried out in 1999-2001 in an Iranian urban population which enrolled 8766 individuals over 20 years. Fasting and 2-h plasma glucose was measured in all subjects after exclusion of diabetic subjects. Logistic regression and receiver operation characteristic (ROC) curve analysis were used to determine the independent clinical risk factors and their optimal cut-points associated with impaired glucose tolerance (IGT) and dysglycemia (IGT or diabetes). RESULTS: Application of the new criteria decreased positive likelihood ratio (LR+) of IFG for detecting IGT (from 6.68 to 3.86) or dysglycemia (from 9.90 to 4.46) but slightly improved their agreement (Kappa increased from 0.158 to 0.286 for IGT and 0.238 to 0.354 for dysglycemia). When the clinical data (age >45 years, BMI >28 kg/m(2) and systolic blood pressure >125 mm Hg) were added to the new criteria, the agreement of IFG with IGT and dysglycemia significantly improved (Kappa=0.470 and 0.574, respectively). This also increased the LR(+) to 14.5 and 17.4, respectively, for detecting IGT or dysglycemia. CONCLUSION: The new IFG definition in combination with common clinical risk factors constitutes a group that most likely predicts IGT or dysglycemia and may be a target for which preventive strategies should be considered. PMID- 17350134 TI - Study of iron metabolism disturbances in an animal model of insulin resistance. AB - The relationship between iron and insulin-resistance (IR) is documented by the positive correlation between iron stores and IR. Moreover, some patients exhibited a hepatic iron overload associated with IR (HIO-IR) but the mechanism involved in this overload is not known. Thus, we studied the iron metabolism disturbances in an animal model of IR and the influence of provoked hyperglycemia/hyperinsulinemia on plasma iron parameters. Wistar rats were fed a control or a high-fat/high-energy (HF/HE) diet. Plasma glucose, insulin, iron, transferrin and transferrin saturation (TS) were measured during intra-peritoneal glucose test tolerance (IPGTT) compared to saline. Hemogram, tissue iron concentrations and hepatic hepcidin mRNA expression were determined at the end of experiment. HF/HE rats exhibited higher body and liver weights, increased IR index and hemoglobin concentration. Iron content was lower in the spleen of HF/HE rats and tended to decrease in the liver as compared to controls. Transferrin values were higher and these of TS lower in HF/HE group. The hepcidin mRNA was 3.5-fold lower in HF/HE rats than in controls. IPGTT had no effect on iron status parameters in both groups. As reflected by higher hemoglobin concentration, IR could increase erythropoiesis which enhances iron requirement. Iron stores and TS value decreased leading to a down-regulation of hepcidin expression which increased iron absorption. Hepcidin expression should be investigated in metabolic syndrome and hepatic iron overload associated with IR. PMID- 17350135 TI - Can plasma glucose and HbA1c predict fetal growth in mothers with different glucose tolerance levels? AB - To assess whether HbA1c and plasma glucose predicts abnormal fetal growth, 758 pregnant women attending 5 Diabetic Centers were screened for gestational diabetes mellitus (GDM). On glucose challenge (GCT) at 24-27 weeks of gestation (g.w.), negative cases formed the normal control group (N1). Positive cases took an oral glucose tolerance test (OGTT): those found negative were classed as false positives screening test (N2); if they had an OGTT result at least as high as their normal glucose levels, they were classed as having one abnormal glucose value (OAV) at OGTT; two values as GDM. HbA1c was assayed on the day of GCT. We considered fetal macrosomia, large for gestational age (LGA), ponderal index and mean growth percentile. Mean age, pre-pregnancy BMI, fasting plasma glucose (FPG) and HbA1c were progressively higher from N1 to GDM patients. The newborn of N2 mothers were heavier than those with N1 or GDM. The mean growth percentile was significantly higher in N2 than in N1. More LGA babies were born to OAV than to N1 or N2 women. Macrosomia and ponderal index did not differ significantly in the four groups. At logistic regression only plasma glucose at GCT could predict LGA babies and a ponderal index above 2.85. At risk analysis, GDM and OAV significantly predicted LGA babies, and GDM a ponderal index >2.85. In conclusion, FPG at GCT could predict fetal overgrowth and plasma glucose >85mg/dl doubles the risk of LGA infants. HbA1c at 24-27g.w. does not predict fetal overgrowth. Mild alterations in glucose tolerance correlate with fetal overgrowth and needs monitoring and treatment. PMID- 17350136 TI - tdc.msm: an R library for the analysis of multi-state survival data. AB - The aim of this paper is to present an R library, called tdc.msm, developed to analyze multi-state survival data. In this library, the time-dependent regression model and multi-state models are included as two possible approaches for such data. For the multi-state modelling five different models are considered, allowing the user to choose between Markov and semi-Markov property, as well as to use homogeneous or non-homogeneous models. Specifically, the following multi state models in continuous time were implemented: Cox Markov model; Cox semi Markov model; homogeneous Markov model; non-homogeneous piecewise model and non parametric Markov model. This software can be used to fit multi-state models with one initial state (e.g., illness diagnosis), a finite number of intermediate states, representing, for example, a change of treatment, and one absorbing state corresponding to a terminal event of interest. Graphical output includes survival estimates, transition probabilities estimates and smooth log hazard for continuous covariates. PMID- 17350137 TI - Stage IA non-small cell lung cancer: vessel invasion is a poor prognostic factor and a new target of adjuvant chemotherapy. AB - This study reports the efficacy of adjuvant chemotherapy in stage IA non-small cell lung cancer (NSCLC) with vessel invasion (Vi). We sub-divided 322 patients with surgically resected pathological stage IA NSCLC into two groups according to Vi [non-Vi (n=237) and Vi (n=85)]. Both groups were compared with regard to age, gender, performance status, smoking habits, serum carcinoembryonic antigen level, extent of surgery, tumour size, histopathology, recurrence sites, and survival. The overall 5-year survival rates of non-Vi and Vi groups were 89.6% and 71.8% (P<0.001), respectively. Distant metastasis was observed more frequently in the Vi group (P<0.001, risk ratio: 9.06). Univariate and multivariable analyses identified poor performance status, squamous cell carcinoma, tumour size>or=15 mm and Vi as poor prognostic factors (P<0.05). The overall 5-year survival rate of stage IA Vi group nearly overlapped with that of patients with stage IB NSCLC. Retrospectively, oral uracil-tegafur chemotherapy increased the overall 5-year survival rate of stage IA Vi group by more than 25% (P=0.036). In conclusion, vessel invasion is a poor prognostic factor in patients with stage IA NSCLC. Prognosis of patients with Vi-stage IA NSCLC is similar to that of patients with stage IB NSCLC and is improved significantly by postoperative oral uracil-tegafur chemotherapy. Our preliminary study suggests that stage IA Vi group benefits from adjuvant chemotherapy. PMID- 17350138 TI - Clonality and heterogeneity of pulmonary blastoma from the viewpoint of genetic alterations: a case report. AB - Biphasic pulmonary blastoma is a rare lung tumor with epithelial and mesenchymal components. Genetic alterations in this tumor are largely unknown, except for the presence of beta-catenin and p53 mutations and the absence of KRAS mutation. To understand the molecular process of histogenesis of this tumor, a whole genome allelic imbalance (AI) scanning using a high-resolution single nucleotide polymorphism array as well as mutational analysis of the p53, EGFR, KRAS and beta catenin genes were performed against the epithelial and mesenchymal components in the primary tumor and a metastatic tumor in a case of pulmonary blastoma. AI at chromosome regions 14q24-q32 and 17p11-p13 and beta-catenin mutation were commonly detected in all tumors. On the other hand, AI at chromosome regions 3p11 p14 and 9p21-p24 and p53 mutation were detected only in the mesenchymal component in the primary tumor but not in the epithelial component in the primary tumor and the brain metastasis. Likewise, AI at chromosome regions 6p24-p25 and 6q14-q27 was detected in the epithelial component in the primary tumor and the brain metastasis but not in the mesenchymal component in the primary tumor. Furthermore, the genetic alterations detected in the metastatic tumor were completely the same as those in the epithelial component in the primary tumor, indicating that a tumor cell(s) in the epithelial component in the primary tumor selectively metastasized to the brain. These results indicate that this biphasic tumor is of monoclonal origin and the phenotypic heterogeneity of the tumor is due to the differences in the accumulated genetic alterations in each component of the tumor. PMID- 17350139 TI - Expression of mitochondrial tatC in Nicotiana tabacum is responsive to benzothiadiazole and salicylic acid. AB - A cDNA, up-regulated upon treatment of tobacco cells with salicylic acid and benzo (1,2,3) thiadiazole-7-carbothioic acid S-methyl ester, was identified by differential RNA display and the full sequence obtained. This mitochondrial gene, twin arginine translocation (tatC), resembles orthologues across different species, including the gene that codes for a sec-independent membrane translocating protein in bacteria. Hypothetical tatC proteins have also been identified in the mitochondria of Arabidopsis thaliana, Oenothera berteriana, Beta vulgaris, Oryza sativa and Marchantia polymorpha. Comparative protein analysis indicates a similar function for the tatC gene. The up-regulation of the tatC gene in a 3kbp transcript was confirmed by RNA gel blot analysis. PMID- 17350140 TI - Direct and indirect effects of obestatin peptides on food intake and the regulation of glucose homeostasis and insulin secretion in mice. AB - Obestatin is a recently discovered peptide hormone that appears to be involved in reducing food intake, gut motility and body weight. Obestatin is a product of the preproghrelin gene and appears to oppose several physiological actions of ghrelin. This study investigated the acute effects of obestatin (1-23) and the truncated form, obestatin (11-23), on feeding activity, glucose homeostasis or insulin secretion. Mice received either intraperitoneal obestatin (1-23) or (11 23) (1 micromol/kg) 4h prior to an allowed 15 min period of feeding. Glucose excursions and insulin responses were lowered by 64-77% and 39-41%, respectively, compared with saline controls. However this was accompanied by 43% and 53% reductions in food intake, respectively. The effects of obestatin peptides were examined under either basal or glucose (18 mmol/kg) challenge conditions to establish whether effects were independent of changes in feeding. No alterations in plasma glucose or insulin responses were observed. In addition, obestatin peptides had no effect on insulin sensitivity as revealed by hypoglycaemic response when co-administered with insulin. Our observations support a role for obestatin in regulating metabolism through changes of appetite, but indicate no direct actions on glucose homeostasis or insulin secretion. PMID- 17350141 TI - S100B content and secretion decrease in astrocytes cultured in high-glucose medium. AB - S100B is an astrocyte calcium-binding protein that plays a regulatory role in the cytoskeleton and cell cycle. Moreover, extracellular S100B, a marker of glial activation in several conditions of brain injury, has a trophic or apoptotic effect on neurons, depending on its concentration. Hyperglycemic rats show changes in glial parameters, including S100B expression. Here, we investigated cell density, morphological and biochemical alterations in primary cortical astrocytes from rats and C6 glioma cells cultured in high-glucose medium. Astrocytes and C6 glioma cells have a reduced content of S100B and glial fibrillary acidic protein when cultured in a high-glucose environment, as well as a reduced content of glutathione and cell proliferation rate. Although these cells have been used indistinctly to study S100B secretion, we observed a contrasting profile of S100B secretion in a high-glucose medium: a decrease in primary astrocytes and an increase in C6 glioma cells. Based on the in vitro neurotrophic effects of the S100B protein, our data suggest that chronic elevated glucose levels affect astrocyte activity, reducing extracellular secretion of S100B and that this, in turn, could affect neuronal activity and survival. Such astrocyte alterations could contribute to cognitive deficit and other impairments observed in diabetic patients. PMID- 17350143 TI - Novel synthetic approach to N-aryl-4-(3-pyridyl)thiazol-2-amine and analogues using HMCM-41 as catalyst, and their biological evaluation as human platelet aggregation inhibitors. AB - A novel synthetic approach to N-aryl-4-(3-pyridyl)thiazol-2-amine and analogues using HMCM-41, a mesoporous aluminosilicate catalyst and their in vitro ADP induced platelet aggregation inhibitory activity on human blood platelets is described. Among the test compounds N-(2'-flourophenyl)-4-(3-pyridyl)thiazol-2 amine (9e) was found to be the most potent, IC(50)=4.84x10(-7)M. PMID- 17350144 TI - [Vogt-Koyanagi-Harada syndrome. Eight cases]. AB - PURPOSE: Vogt-Koyanagi-Harada disease is a rare systemic affection characterised by the association of ocular inflammatory manifestations and extra ocular lesions such as meningismus, tegumentary or auditory findings observed in pigmented population. Auto-immune origin of this syndrome is probable; a T-lymphocyte mediated autoimmune process is directed against an unidentified antigen associated with melanocytes. METHODS: The aim of this retrospective study is to determine their clinical profile in our country. RESULTS: Eight consecutive cases of Vogt-Koyanagi-Harada disease were studied during a 22-year period. All the patients fulfilled the criteria of American Uveitis Society. All patients were female and had bilateral ocular involvement as panuveitis. Retinal serous detachment was observed in 4 patients, meningitis in 6 cases. 7 patients had hearing loss and 5 patients had cutaneous lesions represented by poliosis. Corticosteroids and/or immunosuppressive therapy were administered in all patients leading to improvement in 5 patients. CONCLUSION: Our series are concording with a usually good ocular prognosis. Immunosuppressive therapy should be used early in posterior segment involvement. PMID- 17350142 TI - Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers. AB - The apolipoprotein varepsilon4 allele (APOE*4) is a major genetic risk factor for Alzheimer's disease (AD) and has been associated with altered cortical activation as assessed by functional neuroimaging in cognitively normal younger and older carriers. We chose to evaluate medial temporal lobe (MTL) activation during encoding and recognition using a perspective-dependent (route or survey) visuospatial memory task by monitoring the blood-oxygen-level-dependent (BOLD) fMRI response in older, non-demented APOE*4 carriers (APOE*4+) and non-carriers (APOE*4-). During encoding, the APOE*4- group had greater average task-associated BOLD responses in ventral visual pathways, including the MTLs, as compared to the APOE*4+ group. Furthermore, MTL activation was greater during route encoding than survey encoding on average in APOE*4-, but not APOE*4+, subjects. During recognition, both groups performed similarly and no BOLD signal differences were found. Finally, within-group analysis revealed MTL activation during encoding was correlated with recognition performance in APOE*4-, but not APOE*4+ subjects. Reduced task-associated MTL activation that does not correlate with either visuospatial perspective or task performance suggests that MTL dysregulation occurs prior to clinical symptoms of dementia in APOE*4 carriers. PMID- 17350145 TI - Influenza neuraminidase antibodies provide partial protection for chickens against high pathogenic avian influenza infection. AB - Protection of chickens against avian influenza (AI) is mostly attributed to production of antibodies against the viral glycoprotein hemagglutinin, whereas less is known about the protective role of antibodies to the other surface glycoprotein neuraminidase (NA). Therefore, vaccines encoding NA antigen (e.g., DNA and alphavirus-based virus like replicon particles (VRP)) or baculovirus expressed recombinant NA (rN2) were tested for their ability to protect against highly pathogenic AI (HPAI) in chickens. Vaccination with A/Pheasant/Maryland/4457/93 (Ph/MD) rN2 protein produced significantly higher levels of NA-inhibition (NI) activity and 88% protection from HPAI H5N2 challenge than vaccination with Ph/MD N2 DNA (25% protection). Vaccination with Ph/MD N2 VRP a minimum of two times also produced high levels of NI activity and protection against HPAI challenge (63% protection). Vaccination with VRP encoding an N2 gene that was genetically distant from the challenge virus N2 failed to protect chickens. Vaccines producing higher levels of NI activity conferred partial protection, but failed to affect viral shedding. Consideration of the homology between vaccine and challenge virus isolate NA genes may provide improved immunity if high levels of NI activity are obtained. PMID- 17350146 TI - Radioactivity in the atmosphere over Hong Kong. AB - Upper-air radioactivity soundings have been regularly conducted in Hong Kong since 1994. A total of 38 soundings, measuring the vertical profile of radioactivity in the atmosphere over Hong Kong using on-board Geiger-Mueller tubes, were made during the period 1994-2003 in different seasons and weather conditions. This paper presents the data obtained in Hong Kong and compares the composite vertical profile with observations in other parts of the world. The average Pfotzer maximum over Hong Kong was found to be at an altitude of around 16.1km, lower than those observed at higher latitudes. The variations of the Pfotzer maximum with geomagnetic rigidity and solar activity are discussed. Seasonal and local weather effects on radioactivity in the lower atmosphere were also studied. PMID- 17350147 TI - Availability of radium isotopes and heavy metals from scales and tailings of Polish hard coal mining. AB - Radium and heavy metal contaminated tailings and scales resulting from Polish hard coal mining were investigated for their mobilisation potential by using leaching methods. The main focus is set on a three-step extraction procedure proposed by BCR (Bureau Communautaire de Reference, now Standards Measurements and Testing Programme) of the European Union, which was used for investigating the availability of radium isotopes. In addition, the results of a Polish extraction procedure for the heavy metals' water solubility are presented for rough comparison. After a special treatment, the BCR-reagents were measured by gamma-spectrometry to define their radium activity concentrations; the heavy metal content in the water soluble fractions was determined by ICP-AES. The samples were collected at two different sites influenced by the discharge of pit water from hard coal mining. The tailings were taken from a former tailing pond, which now is no longer in use, but the settled material is still present. At another abandoned and meanwhile flooded tailing pond, the scales were scraped from the inside of a discharge tube. The results obtained show that there is different leaching behaviour between the radium isotopes. The tailings being characterised by surface adsorbed radium provide up to 25% of the initial (226)Ra content, (228)Ra is altogether leached up to 15%. The scales comprise stable radiobaryte (Ba[Ra]SO(4)) and can be considered as being unable to provide radium isotopes, since no trace of radium dissolution was observed. The leaching behaviour of heavy metals is similar to that of radium. Mn, Ni and Zn are dissolved by water from the tailings; the scales do not provide any. PMID- 17350148 TI - Elevated concentrations of primordial radionuclides in sediments from the Reedy River and surrounding creeks in Simpsonville, South Carolina. AB - A gamma-ray survey and analysis of 16 riverbed samples from the Reedy River watershed near Simpsonville, SC were conducted and compared with national and international studies of primordial radionuclides. The study reported here follows on a recent discovery of anomalously high uranium concentrations in several private well waters in the area. An HPGe spectrometer was used for quantification of gamma emitting radionuclides in the sediments. All sediments contained radionuclides from the uranium and thorium series as well as (40)K. Uranium-238 concentrations in sediment samples ranged from 11.1 to 74.2Bqkg(-1). The measured radionuclide concentrations were compared with data from UNSCEAR and NURE reports. The river and stream sediment data were augmented by in situ NaI(Tl) gamma-ray spectrometer measurements. Comparisons between the ex situ and in situ measurements indicate equivalently distributed uranium in the surface soils and stream sediments, the source of which is likely attributed to the monazite belts that are known to exist in the area. PMID- 17350149 TI - A chylous cyst at the right base of the neck. AB - A case is presented of a cystic lesion, which presented at the base of the right side of the neck. The lesion was more obvious on forced expiration. Aspiration revealed chylous fluid and a Magnetic Resonance Imaging (M.R.I.) scan revealed a well-circumscribed cystic lesion with no deeper extension. So far, this chylous cyst has not required treatment, but is being kept under regular review. PMID- 17350150 TI - Biomechanical comparison of extended trochanteric osteotomy and slot osteotomy for femoral component revision in total hip arthroplasty. AB - BACKGROUND: Depending upon the clinical presentation and need for exposure in revision hip arthroplasty, an extended trochanteric osteotomy or slot osteotomy could be used for removal of an inaccessible distal cement mantle, infected material, or distal fragment of a broken stem. This study is a biomechanical comparison of these two osteotomy techniques. METHODS: A press-fit femoral component with a 20-cm straight stem was implanted in each of ten synthetic femurs. The stiffness of these components implanted in the femurs was measured for a compressive load condition simulating the stance phase of level walking. Half of the femurs then received an extended trochanteric osteotomy, and the other half a slot osteotomy. Stiffness testing was repeated both after the osteotomized bone was removed, and after it was fixed back in place by cerclage wiring. FINDINGS: The stiffness of the femoral component/synthetic femur constructs in the slot osteotomy group was significantly greater than in the extended trochanteric osteotomy group. INTERPRETATION: This study demonstrated that in the laboratory setting, the slot osteotomy was significantly stiffer than the more traditional extended trochanteric osteotomy. However, the clinical implications of this increased stiffness are unknown. The ultimate choice of the type of osteotomy depends upon the exposure requirements for a given clinical situation. PMID- 17350151 TI - The inhibitory mechanism of methylmercury on differentiation of human neuroblastoma cells. AB - Methylmercury (MeHg) is a ubiquitous environmental toxicant and shows neurotoxicity to central nerve system (CNS) or neuronal cells. It has been known that MeHg has more influence to developing or differentiating CNS/neuronal cells than adult or differentiated CNS/neuronal cells. This study examined the effect of MeHg on differentiation of human neuroblastoma SH-SY5Y cells induced by all trans-retinoic acid (RA). MeHg caused the impairment of the RA-induced G(1/0) phase arrest; it was induced the reduction of G(1/0) phase and S phase arrest. Extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase C (PKC) are involved in the RA-mediated differentiation and cell cycle progression. Activation of ERK1/2 by RA was increased more in MeHg-treated differentiating cells, comparing with only RA-treated groups. Furthermore, in both cases of inhibition of ERK1/2 with PD98059 or inhibition of PKC with GF109203X, RA/MeHg induced ERK1/2 phosphorylation was reduced and G(1/0) phase arrest was induced. Thus, it indicates that the neuronal differentiation with RA was mediated by the ERK1/2 and PKC related pathway and MeHg resulted in neurotoxic influences through the disturbance in steps of differentiation by this pathway. These results suggest that MeHg inhibits RA-induced differentiation in SH-SY5Y cells by a pathway dependent ERK1/2 and PKC. PMID- 17350152 TI - The effects of sugar-free chewing gums on dental plaque regrowth: a comparative study. AB - Sugar-free chewing gum has been claimed to be a useful means of reducing dental plaque accumulation. The incorporation of additives, such as enzymes, abrasives and divalent metal ions, into gum formulations might improve their antiplaque activity, particularly at the buccal and lingual surfaces of the teeth. OBJECTIVES: The aim of this study was to investigate the plaque inhibitory effects of three sugar-free chewing gums each containing lactoperoxidase (LP), micro granules of silicon dioxide (SD), and zinc gluconate (ZG). METHODS: The study was an observer-masked, randomized cross-over design balanced for carryover effects, involving 12 healthy volunteers in a 4-day plaque regrowth model. An additive-free (AF) gum served as positive/negative control for occlusal and smooth surfaces, respectively. On day 1, subjects received professional prophylaxis, suspended oral hygiene measures, and commenced chewing their allocated product. Gum chewing was one piece chewed for 30min 4 times a day. On day 5, subjects were scored for disclosed plaque. RESULTS: There were no significant differences in antiplaque activity of the gums tested, neither for the smooth nor for the occlusal surfaces (P=0.447 and P=0.418, respectively). Similar results were obtained for the anterior and posterior sites of smooth surfaces (P>0.05), and for the lower and upper sites of occlusal surfaces (P=0.451 and P=0.53, respectively). CONCLUSIONS: These findings suggest that the chewing gums containing LP, SD and ZG would provide no plaque inhibitory effects on smooth surfaces. The gums containing these additives, therefore, should not be recommended as adjuncts to mechanical oral hygiene. PMID- 17350153 TI - Stress during development: Impact on neuroplasticity and relevance to psychopathology. AB - Development represents a critical moment for shaping adult behavior and may set the stage to disease vulnerability later in life. There is now compelling evidence that stressful experiences during gestation or early in life can lead to enhanced susceptibility for mental illness. In this paper we review the data from experimental studies aimed at investigating behavioral, hormonal, functional and molecular consequences of exposure to stressful events during prenatal or early postnatal life that might contribute to later psychopathology. The use of the newest methodology in the field and the intensive efforts produced by researchers have opened the possibility to reveal the complex, finely tuned and previously unappreciated sets of molecular interactions between different factors that are critical for neurodevelopment thus leading to important discoveries regarding perinatal life. The major focus of our work has been to revise and discuss data from animal studies supporting the role of neuronal plasticity in the long-term effects produced by developmental adversities on brain function as well as the possible implications for disease vulnerability. We believe these studies might prove useful for the identification of novel targets for more effective pharmacological treatments of mental illnesses. PMID- 17350154 TI - Brain potentials reflect access to visual and emotional memories for faces. AB - Familiar faces convey different types of information, unlocking memories related to social-emotional significance. Here, the availability over time of different types of memory was evaluated using the time-course of P3 event related potentials. Two oddball paradigms were employed, both using unfamiliar faces as standards. The infrequent targets were, respectively, artificially-learned faces (devoid of social-emotional content) and faces of acquaintances. Although in both tasks targets were detected accurately, the corresponding time-course and scalp distribution of the P3 responses differed. Artificially-learned and acquaintance faces both elicited a P3b, maximal over centro-parietal sites, and a latency of 500ms. Faces of acquaintances elicited an additional component, an early P3 maximal over frontal sites: with a latency of 350ms. This suggests that visual familiarity can only trigger the overt recognition processes leading to the slower P3b, whereas emotional-social information can also elicit fast and automatic assessments (indexed by the frontal-P3) crucial for successful social interactions. PMID- 17350155 TI - The role of beta93 Cys in the inhibition of Hb S fiber formation. AB - Recent studies have suggested that nitric oxide (NO) binding to hemoglobin (Hb) may lead to the inhibition of sickle cell fiber formation and the dissolution of sickle cell fibers. NO can react with Hb in at least 3 ways: 1) formation of Hb(II)NO, 2) formation of methemoglobin, and 3) formation of S-nitrosohemoglobin, through nitrosylation of the beta93 Cys residue. In this study, the role of beta93 Cys in the mechanism of sickle cell fiber inhibition is investigated through chemical modification with N-ethylmaleimide. UV resonance Raman, FT-IR and electrospray ionization mass spectroscopic methods in conjunction with equilibrium solubility and kinetic studies are used to characterize the effect of beta93 Cys modification on Hb S fiber formation. Both FT-IR spectroscopy and electrospray mass spectrometry results demonstrate that modification can occur at both the beta93 and alpha104 Cys residues under relatively mild reaction conditions. Equilibrium solubility measurements reveal that singly-modified Hb at the beta93 position leads to increased amounts of fiber formation relative to unmodified or doubly-modified Hb S. Kinetic studies confirm that modification of only the beta93 residue leads to a faster onset of polymerization. UV resonance Raman results indicate that modification of the alpha104 residue in addition to the beta93 residue significantly perturbs the alpha(1)beta(2) interface, while modification of only beta93 does not. These results in conjunction with the equilibrium solubility and kinetic measurements are suggestive that modification of the alpha104 Cys residue and not the beta93 Cys residue leads to T-state destabilization and inhibition of fiber formation. These findings have implications for understanding the mechanism of NO binding to Hb and NO inhibition of Hb S fiber formation. PMID- 17350156 TI - DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery studied by circular dichroism and other biophysical techniques. AB - Cationic liposomes give rise to stable complexes with DNA molecules (lipoplexes) that are of great interest for gene delivery applications. In particular, liposomes made up by a cationic lipid (DOTAP or DC-Chol) and a zwitterionic lipid (DOPE), produce stable adducts with single and double-stranded DNA oligonucleotides. Formation of these lipoplexes has been further addressed here by circular dichroism spectroscopy (CD) and by other independent biophysical methods. Titration of DNA oligonucleotides with cationic liposomes resulted into significant modifications of their circular dichroic bands. Such spectral modifications were ascribed to progressive DNA condensation and loss of native conformation, as a consequence of the electrostatic interactions taking place between the phosphate groups of DNA and the positively charged head groups of cationic lipids. In all cases, the loss of the CD feature characteristic of the native DNA conformation closely matched the inflection point of Zeta potential profiles. The resulting adducts showed peculiar and non-canonical CD spectra, while exhibiting appreciable stability at physiological pH. PMID- 17350157 TI - Assessing the efficiency gains of improved spatial targeting of policy interventions; the example of an agri-environmental scheme. AB - GIS-based spatial targeting is increasingly recognised as a potentially useful tool to design more efficient policy interventions. The use of this tool has also been advocated in the context of incentive-based agri-environmental schemes, but there has been little work to date to estimate the level of efficiency gains which it may help to achieve. This paper investigates the requirements to arrive at such estimates, using a Scottish farm woodland scheme as a case study. This agri-environmental scheme aims to provide visual amenity and biodiversity. Maps of these two benefits are used to develop improved spatial targeting scenarios that deliver significant efficiency gains in comparison to the existing scheme design. The paper discusses the nature of the spatial distribution of the relevant benefits at the landscape scale and the data requirements for the realistic estimation of efficiency gains. It concludes that although much work needs to be done, the methods available today could and should play a much greater role in improving the landscape-scale design of existing land use schemes focused on the delivery of non-market benefits. PMID- 17350158 TI - Methodology for quantifying interactions between perfusion evaluated by DCE-US and hypoxia throughout tumor growth. AB - The objective was to validate a combination of two new technologies to depict tumor physiology both temporally and spatially with dynamic contrast-enhanced sonography and an oximeter. Human cancer prostate tumors xenografted onto mice were followed for three weeks using dynamic contrast-enhanced ultrasonography (DCE-US) to detect tumor perfusion. Time intensity curves in linear data were quantified on four regions-of-interest (ROI, main tumor section and its anterior, central and posterior intra-tumoral areas) to extract three indices of perfusion. An oxygen sensor was guided by sonography to obtain accurate pO(2) measurements in the three predefined areas of tumors during their development. No impact on tumor growth of subsequent pO(2) probe insertion was detected. Among the four ROIs studied, the local central tumor showed significant perfusion and oxygenation variations throughout the experiment. A correlation was observed between local central tumor perfusion and pO(2), both of them decreasing through time (p = 0.0068; r = 0.66). The methodology which we developed demonstrated the potential of combining DCE-US with direct tissue pO(2) measurements, improving the description of complex intratumoral dynamic behavior. PMID- 17350160 TI - Functional analysis of LHbeta knockout mice. AB - LH and FSH act on gonadal cells to regulate steroidogenesis and gametogenesis. To model human reproductive disorders involving loss of LH function and to define LH responsive genes, we produced knockout mice lacking the hormone-specific LHbeta subunit. LHbeta null mice are viable but demonstrate postnatal defects in gonadal growth and function resulting in infertility. Mutant males have decreased testes size, a block in Leydig cell differentiation, and a reduction in serum and intra testicular testosterone levels. Furthermore, spermatogenesis is blocked at the round spermatid stage resulting in a total absence of the elongated spermatids. Mutant female mice are hypogonadal and demonstrate decreased levels of serum estradiol and progesterone. Ovarian histology reveals normal thecal layer, defects in folliculogenesis including many degenerating antral follicles and absence of corpora lutea. The defects in both sexes are not secondary to aberrant FSH regulation, since FSH levels were unaffected in null mice. Finally, the null mice can be pharmacologically rescued by exogenous hCG indicating that LH responsiveness of the target cells is not irreversibly lost. Thus, LHbeta null mice provide a useful model to study the consequences of an isolated deficiency of LH ligand in reproduction, while retaining normal LH-responsiveness in target cells. PMID- 17350159 TI - Is the sexual function compromised in long-term testicular cancer survivors? AB - OBJECTIVES: This study explores sexual function in a large unselected sample of Norwegian testicular cancer survivors (TCSs) by comparing the results with population data. METHODS: The study included 1084 TCSs aged 20-59 yr with mean follow-up time of 11.1 (range: 5-21) yr. They provided information about their medical, social, lifestyle, and familial situations on a questionnaire that included the Brief Male Sexual Function Inventory (BSFI). Outcome measures were mean BSFI domain scores and BSFI-based prevalence rates of sexual problems. The BSFI findings of an age-adjusted random sample of the Norwegian male population (N=929) constituted normative data (NORM). Descriptive statistics and logistic regression analyses were applied, and a significance level of <0.01 was applied. RESULTS: Compared with NORM, TCSs had significantly worse scores on ejaculatory and sexual problems in both young (20-39 yr) and middle-aged (40-59 yr) groups. In the young group, sexual satisfaction was significantly better in TCSs versus NORM. Overall sexual problems were expressed by 38.8% of the TCSs versus 35.5% in NORM. In multivariate analyses, overall sexual problems in TCSs were significantly associated with increasing age, lack of a partner, and a higher anxiety score, while ejaculation problems showed significant association with lack of a partner, and a trend for chemotherapy and neurotoxic side effects (p=0.02). CONCLUSIONS: Compared with NORM, ejaculatory function was compromised in TCSs. Overall sexual problems in TCSs were associated with factors also observed in NORM. Better sexual satisfaction in young TCSs compared with NORM should be noted. PMID- 17350161 TI - Juvenile Behcet's disease: highlighting neuropsychiatric manifestations and putative genetic mechanisms. AB - Behcet's disease is a multisystem inflammatory disorder of unknown etiology. We report a 12-year-old boy who presented with features of raised intracranial tension and seizures and was found to have cerebral venous sinus thrombosis on evaluation. Behcet's disease was diagnosed based on occurrence of recurrent oral and genital ulcers in the past and characteristic skin lesions subsequently. He also showed significant personality changes including multiple attempts of deliberate self-harm. Pedigree analysis revealed that six family members spanning three generations had recurrent oral ulcers and three members satisfied the criteria for Behcet's disease. Clinical features varied amongst the family members and there was suggestion of genetic anticipation. The index case was carrying HLA-B37/B7 and the mother was carrying B37/B40. Our report sheds light on the genetics of Behcet's disease. Unusual features were early age of onset, cerebral venous sinus thrombosis, significant personality changes and strong family history with phenotypic heterogeneity. PMID- 17350162 TI - Indications for brain CT scan in patients with minor head injury. AB - OBJECTIVES: Minor head injury is the most common type of head injury. Despite of high incidence and numerous studies performed, there is much controversy about correct evaluation of these patients. The aim of this study was to find clinical signs and symptoms which help to predict the indications for brain CT scan following minor head injury. METHODS: A series of 682 consecutive patients who had been attended at two university hospitals (Alzahra and Kashani) with minor head injury (GCS=15) were prospectively enrolled in this cohort study. In all cases clinical signs and symptoms were collected and a cranial computerized tomography (CT) scan was obtained. The relationship between the occurrence of clinical findings and appearance of intracranial posttraumatic lesions on cranial CT was analyzed by chi-square tests and statistic logistic regression methods, with 95% confidence intervals. RESULTS: Of 682 patients, 46 (6.7%) presented brain injuries on CT scan. All patients with abnormal CT scans had at least one of the following factors (risk factors): posttraumatic amnesia, loss of consciousness, posttraumatic seizure, headache, vomiting, focal neurological deficit, skull fracture, coagulopathy or antecedent of treatment with anticoagulants and patient age older than 60 years. No abnormal CT scans were found among patients without any of those risk factors on admission. Vomiting, skull fracture and age greater than 60 years were risk factors significantly correlated to an abnormal cranial CT after head injury. The presence of several risk factors in a patient increased the probability of posttraumatic lesion on CT scan. CONCLUSION: Some clinical risk factors can be used as a guide to predict the probability of abnormal CT following minor head injury. PMID- 17350163 TI - Positive regulation of deoxycytidine kinase activity by phosphorylation of Ser-74 in B-cell chronic lymphocytic leukaemia lymphocytes. AB - Deoxycytidine kinase (dCK) activates several antileukaemic nucleoside analogues. We have recently reported that the activity of dCK, overexpressed in HEK 293T cells, correlates with its phosphorylation level on Ser-74. Here, we show that dCK from B-cell chronic lymphocytic leukaemia (B-CLL) lymphocytes can be detected by an anti-phospho-Ser-74 antibody and that interindividual variability in dCK activity is related to its phosphorylation level on Ser-74. Moreover, pharmacological intervention modified Ser-74 phosphorylation, in close parallel with changes in dCK activity. These results suggest that activation of dCK via phosphorylation of Ser-74 might constitute a new therapeutic strategy to enhance activation and efficacy of nucleoside analogues. PMID- 17350164 TI - PAX3 and PAX3-FKHR promote rhabdomyosarcoma cell survival through downregulation of PTEN. AB - PAX3 or PAX3-FKHR expression is implicated in cell transformation and tumourigenesis. Here, C2C12 myoblasts were transfected with a sense Pax3 vector and a pTet-On system to induce Pax3 expression, whereas to downregulate PAX3 FKHR, Rh18 was transfected with an antisense Pax3 with a pTet-On system. The inhibition of PAX3-FKHR in Rh18 induced upregulation of PTEN. Decreased resistance to apoptosis and increased transformation ability were observed in the Rh18 cells with PAX3-FKHR downregulation. Conversely, Pax3 induction in C2C12 cells downregulated the expression of PTEN and p27(Kip1). These results indicate that the involvement of PAX3 and PAX3-FKHR in rhabdomyosarcoma tumourigenesis may be through downregulation of PTEN tumour suppressor gene, affecting the PTEN/AKT survival pathway. PMID- 17350165 TI - Concentration and speciation of heavy metals in six different sewage sludge composts. AB - This study presents the concentrations and speciation of heavy metals (HMs) in six different composts of sewage sludges deriving from two wastewater treatment plants in China. After 56 days of sludge composting with rice straw at a low C/N ratio (13:1), cadmium (Cd), copper (Cu), lead (Pb) and zinc (Zn) were enriched in sludge composts, exhibiting concentrations that varied from 0.75 to 2.0, 416 to 458, 66 to 168 and 1356 to 1750mgkg(-1) dry weight (d.w.), respectively. The concentrations increased by 12-60% for Cd, 8-17% for Cu, 15-43% for Pb and 14-44% for Zn compared to those in sewage sludges. The total concentrations of individual or total elements in the final composts exceeded the maximum permissible limits proposed for compost or fertilizer. In all the final composts, more than 70% of total Cu was associated with organic matter-bound fraction, while Zn was mainly concentrated in exchangeable and Fe-Mn oxide-bound fractions which implied the high mobility and bioavailability. Continuously aerated composting treatment exhibited better compost quality and lower potential toxicity of HMs, whereas inoculant with microorganism and enzyme spiked during composting had no obvious advantage on humification of organic matter and on reducing HM mobility and bioavailability. PMID- 17350166 TI - Comparison of nutrients degradation in small scale membrane bioreactors fed with synthetic/domestic wastewater. AB - Two membrane bioreactors were operated with biological phosphorus removal, carbon degradation and denitrification to check how comparable and representative they were compared to full-scale plants. One was fed with synthetic municipal wastewater and was switched from pre- to post-denitrification without carbon dosing. The influent of the second plant was drawn from a separate sewer. This plant worked the whole time with post-denitrification without carbon dosing. The synthetic wastewater was designed to achieve a realistic COD:TN:TP ratio and tested for long time biodegradability. The eliminations were >94% (COD) and >97% (TP) for both plants. This was within the range of commercial plants, as well as the TN elimination for the pre-denitrification of plant I (>75%). The eliminations of TN for post-denitrification were above 80% for both plants despite the high influent concentrations and the missing carbon source for post DN. A calculation of the nitrification rates gave values similar to those found in literature (1-6 mgN/(gMLVSSh)). A comparison of the denitrification showed expected rates for pre-denitrification (7.5 mgN/(gMLVSSh)) for plant I. The values (on average 1.8 mgN/(gMLVSSh)) for post-denitrification in plant II were higher than endogenous denitrification rates which are commonly reported as 0.2 0.8 mgN/(gMLVSSh). The rates for post-denitrification in plant I were only slightly higher than endogenous ones (0.9 mgN/(gMLVSSh)). PMID- 17350167 TI - Elevated plasma N-terminal ProBNP levels in unmedicated patients with major depressive disorder. AB - There is considerable evidence that cardiovascular diseases are more prevalent in patients with major depressive disorder (MDD). Secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) increases in several cardiac illnesses, making this neurohormone a reliable diagnostic and prognostic biomarker of cardiovascular risk. We measured plasma NT-proBNP levels in the following three groups of subjects free of overt cardiovascular disease: unmedicated patients with MDD (n=40), unmedicated patients with schizophrenia (n=44), and normal control subjects (n=42). The severity of depressive symptoms was rated using the Hamilton Depression Rating Scale (HAMD). Plasma NT-proBNP levels were assayed by ELISA. Plasma NT-proBNP levels were significantly higher in the MDD group (median: 217.1 pmol/L; interquartile range: 179.4-277.1 pmol/L) than in patients with schizophrenia (175.7 pmol/L [139.0-218.9]; P<0.05) or in the control group (158.9 pmol/L [98.3-212.1]; P<0.001). Among patients with MDD, there was a significant positive correlation (Spearman's rank correlation=0.422, P=0.008) between plasma NT-proBNP and HAMD scores. Altogether, our results indicate that elevated NT-proBNP levels may play a role in linking MDD with increased cardiovascular risk. PMID- 17350168 TI - Nonlinear EEG activation evoked by low-strength low-frequency magnetic fields. AB - Recent electrophysiological evidence suggested the existence of a human magnetic sense, but the kind of dynamical law that governed the stimulus-response relationship was not established. We tested the hypothesis that brain potentials evoked by the onset of a weak, low-frequency magnetic field were nonlinearly related to the stimulus. A field of 1G, 60 Hz was applied for 2s, with a 5s inter stimulus period, and brain potentials were recorded from occipital electrodes in eight subjects, each of whom were measured twice, with at least 1 week between measurements. The recorded signals were subjected to nonlinear (recurrence analysis) and linear (time averaging) analyses. Using recurrence analysis, magnetosensory evoked potentials (MEPs) were detected in each subject in both the initial and replicate studies, with one exception. All MEPs exhibited the expected latency but differed in dynamical characteristics, indicating that they were nonlinearly related to the stimulus. MEPs were not detected using time averaging, thereby further confirming their nonlinearity. Evolutionarily conditioned structures that help mediate linear field-transduction in lower life forms may be expressed and functionally utilized in humans, but in a role where they facilitate vulnerability to man-made environmental fields. PMID- 17350169 TI - Mental disorders among persons with chronic back or neck pain: results from the World Mental Health Surveys. AB - This paper reports cross-national data concerning back or neck pain comorbidity with mental disorders. We assessed (a) the prevalence of chronic back/neck pain, (b) the prevalence of mental disorders among people with chronic back/neck pain, (c) which mental disorder had strongest associations with chronic back/neck pain, and (d) whether these associations are consistent across countries. Population surveys of community-dwelling adults were carried out in 17 countries in Europe, the Americas, the Middle East, Africa, Asia, and the South Pacific (N=85,088). Mental disorders were assessed with the Composite International Diagnostic Interview, third version (CIDI 3.0): anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, posttraumatic stress disorder, and social anxiety disorder), mood disorders (major depression and dysthymia), and alcohol abuse or dependence. Back/neck pain was ascertained by self-report. Between 10% and 42% reported chronic back/neck pain in the previous 12 months. After adjusting for age and sex, mental disorders were more common among persons with back/neck pain than among persons without. The pooled odds ratios were 2.3 [95% CI=2.1-2.5] for mood disorders, 2.2 [95% CI=2.1-2.4] for anxiety disorders, and 1.6 [95% CI=1.4-1.9] for alcohol abuse/dependence in people with versus without chronic back/neck pain. Although prevalence rates of back/neck pain were generally lower than in previous reports, mental disorders were associated with chronic back/neck pain. The strength of association was stronger for mood and anxiety disorders than for alcohol abuse/dependence. The association of mental disorders with back/neck pain showed a consistent pattern across both developed and developing countries. PMID- 17350170 TI - Site-specific fracture plane determination using the FIB/TEM. AB - A new method for the determination of the crystallographic indices of planar fracture surfaces is described. The key innovation is the use of a focused ion beam instrument to extract two transmission electron microscopy (TEM) foils from the fracture surface. Selected area diffraction of these foils in the TEM allows the determination of the fracture plane from the cross product of two crystallographic line directions contained within the plane. This allows the indices to be determined from relatively small fracture surfaces, affording fracture plane determinations from facets on polycrystalline samples. The validation of this method using cleavage fracture in pure zinc is described. PMID- 17350171 TI - The strong localization of surface plasmon polariton on a metal-coated tip of optical fiber. AB - It is shown that during the propagation of surface plasmon polariton (SPP) on a metal-coated tip of an optical fiber its wavelength essentially decreases and wave fields anomalously increase. Dependence of a degree of localization of SPP on sharpness of the structure and width of the metal layer is defined. The received results can be used to increase the resolution of scanning optical microscope. PMID- 17350172 TI - A new method based on image analysis for determining cyanobacterial biomass by CLSM in stratified benthic sediments. AB - Cyanobacteria are the dominant primary producers in microbial mats, which are stratified benthic microbial ecosystems found in coastal environments. Some cyanobacteria form long filaments, which make difficult to apply classical methods to estimate their biomass because they establish strong interactions with detritic particles. In a previous study, we described a method for determining cyanobacterial biomass by means of confocal laser scanning microscopy (CLSM). However, the manual method used, based on summa projection images, was difficult to apply when analyzing a large number of samples. In this paper, we described a new automated method, based on stacks and applying the plugin voxel counter in the ImageJ analysis system, more adequate for obtaining biomass data quickly from a large number of CLSM images. PMID- 17350173 TI - A bio-mathematical model of time prediction in corneal angiogenesis after alkali burn. AB - BACKGROUND: The determination of angiogenesis time is the key prerequisite to obtaining a balance between valid repair and excessive angiogenesis in wound healing. The aim of the investigation was to establish a bio-mathematical model predicting corneal angiogenesis time after alkali burn by back propagation neural network (BP neural network). METHODS: The corneas of mice in 24 groups were burned by 0.01 mol/l NaOH. Five mice in each group were sacrificed at 6h after alkali burn. The expression levels of vegf and tsp2, determined by real-time quantitive PCR, were used as input vectors in BP neural network. Meanwhile, the corneal angiogenesis of other mice, inspected every 3h in 24 groups till the angiogenesis time were determined, served as output vectors. The data of 18 groups were randomly chosen for network adaptation while that of other 6 groups for simulation forecasting with functions of minmax (), postreg, prepca, trapca, respectively. RESULTS: A bio-mathematical model of two-level BP neural network was established, for its purpose to predict the angiogenesis time through the expression values of vegf and tsp2. The performance index (0.00999996) was smaller than the target value (0.01) after adapting 36,557 times and the accuracy rate of this predict system was 83.33%. Furthermore, the ideal regression line and the optimization regression line were almost coincident (R=0.988 in network adaptation and R=0.793 in simulation forecasting). CONCLUSIONS: The investigation indicated that the bio-mathematical model had available performance of simulation and forecasting. It might provide a novel method to solve clinical problems. PMID- 17350174 TI - Reduced basal and lipopolysaccharide-stimulated adenosine A1 receptor expression in the brain of nuclear factor-kappaB p50-/- mice. AB - Adenosine promotes cytoprotection under conditions of infection, ischemic preconditioning and oxidative stress. Previous studies from our laboratory indicate that the expression of the adenosine A1 receptor (A1AR) is induced by oxidative stress via activation of nuclear factor (NF)-kappaB. The prototypic transcription factor is composed of homo- or heterodimers of p50 and p65 subunits. To determine the role of NF-kappaB in the regulation of the A1AR in vivo, we compared the A1AR RNA and protein levels in the brains of mice lacking the p50 subunit of NF-kappaB (p50-/- mice) and age-matched B6129PF2/J (F2) controls. Radioligand binding assays in the cortex revealed a significantly lower number of A(1)AR (maximal binding capacity, Bmax) in the cortex of p50-/- mice (151+/-62 fmol/mg protein) versus 479+/-181 fmol/mg protein in the F2 (N=5 per strain, P<0.05), but no change in the equilibrium dissociation constant. Similar reductions in A1AR were measured in the hippocampus, brain stem and hypothalamus and in peripheral tissues, such as the adrenal gland, kidney and spleen. Estimation of the A1AR following purification by antibody affinity columns also indicated reduced A1AR in the p50-/- mice cortex, as compared with the F2 mice. A1AR immunocytochemistry indicates distinct neuronal labeling in the F2 cortex, which was substantially reduced in similar sections obtained from p50-/- mice. The p50-/- mice expressed lower levels of A1AR mRNA than F2 mice, as determined by real time PCR. Quantitation of the A1AR transducing G proteins by Western blotting show significantly less Galphai3, no change in Galphai1, but higher levels of Galphao and Gbeta in the cortices of p50-/-, as compared with F2 mice. Administration of bacterial lipopolysaccharide (LPS), an activator of NF-kappaB, increased A1AR expression in the cortices of F2 mice but not p50-/- mice. Cortical neurons cultures prepared from p50-/- mice showed a greater degree of apoptosis, compared with neurons from F2 mice. Activation of the A1AR reduced apoptosis with greater efficacy in cultures from F2 than p50-/- mice. Taken together, these data support a role for NF-kappaB in determining both the basal and LPS-stimulated A1AR expression in vivo which could contribute to neuronal survival. PMID- 17350175 TI - Coffee, stress and cortisol in nursing staff. AB - According to cognitive activation theory, long-lasting work demands without rest or lack of coping may lead to sustained activation and pathology. Cortisol is one of the most important stress hormones in humans and increased basal levels of cortisol are considered a valid marker for sustained activation. In order to investigate this association further, we investigate the relationships between salivary cortisol profiles, job stress, work load (effort/reward, demand/control) and health (subjective health complaints and health-related quality of life) in a population of health care workers. Forty-four women filled in a questionnaire and collected five saliva samples on two consecutive working days (1: wake-up time, 2: wake-up time+30 min, 3: wake-up time+45 min, 4: 1500 h and 5: 2200 h). There was no relationship between psychosocial factors at work and cortisol levels in the morning (cortisol level at wake-up time and awakening cortisol response (ACR)). Only the confounding variable tobacco reached a significant level in the hierarchical regressions analyses. Our significant findings are limited to the afternoon decline and the evening values. The decrease during the day relates to decision authority, physical functioning, general health, and vitality in the single, unadjusted regression analyses. The decrease also relates to coffee intake, which we included originally as a confounding variable. In the final hierarchical regression of the evening values, only decision authority and coffee were significantly related to cortisol levels in the evening. PMID- 17350176 TI - The potential benefits of green tea in patients with uveitis. PMID- 17350177 TI - The risk of early and late lung sequelae after conformal radiotherapy in breast cancer patients. AB - PURPOSE: To study the risks of early and late radiogenic lung damage in breast cancer patients after conformal radiotherapy. METHODS AND MATERIALS: Radiogenic lung sequelae were assessed prospectively in 119 patients by means of clinical signs, radiologic abnormalities, and the mean density change (MDC) of the irradiated lung on CT. RESULTS: Significant positive associations were detected between the development of lung abnormalities 3 months or 1 year after the radiotherapy and the age of the patient, the ipsilateral mean lung dose (MLD), the radiation dose to 25% of the ipsilateral lung (D(25%)) and the volume of the ipsilateral lung receiving 20 Gy (V(20 Gy)). The irradiation of the axillary and supraclavicular lymph nodes favored the development of pneumonitis but not that of fibrosis. No relation was found between the preradiotherapy plasma TGF-beta level and the presence of radiogenic lung damage. At both time points, MDC was strongly related to age. Significant positive associations were demonstrated between the risks of pneumonitis or fibrosis and the age of the patient, MLD, D(25%), and V(20 Gy). A synergistic effect of MLD, D(25%), and V(20 Gy) with age in patients older than 59 years is suggested. CONCLUSION: Our analyses indicate that the risks of early and late radiogenic lung sequelae are strongly related to the age of the patient, the volume of the irradiated lung, and the dose to it. PMID- 17350178 TI - Antinociceptive effect and acute toxicity of the essential oil of Hyptis fruticosa in mice. AB - The essential oil of the Hyptis fruticosa leaves was analyzed by GC/MS and evaluated for antinociceptive property as well as acute toxicity in mice. The essential oil, at doses of 100, 200, and 400 mg/kg (s.c.), produced significant inhibition of acetic acid-induced writhing, but did not manifest a significant effect in hot-plate test. There was no acute toxicity at doses up to 5 g/kg. Bicyclogermacrene, 1,8-cineole, alpha-pinene, and beta-caryophyllene were the major compounds detected in the essential oil. PMID- 17350179 TI - Anti-TB activity of Evodia elleryana bark extract. AB - An ethyl acetate extract of bark from Evodia elleryana produced significant growth inhibition of Mycobacterium tuberculosis at concentrations only minimally inhibitory to human T cells. The crude extract yielded 95% inhibition of TB at 50 microg/ml. The crude extract yielded 29% growth inhibition of human T-cells in culture at that concentration. PMID- 17350180 TI - Increased QT interval variability index in acute alcohol withdrawal. AB - OBJECTIVE: Acute alcohol withdrawal is associated with increased cardiovascular mortality, most likely due to cardiac arrhythmias. As the QT interval reflects the most critical phase for the generation of reentry and thus for arrhythmia, we examined QT variability in patients suffering from acute alcohol withdrawal. METHODS: High resolution electrocardiographic recordings were performed in 18 male unmedicated patients suffering from acute alcohol withdrawal, 18 matched controls and 15 abstained alcoholics. From these, parameters of beat-to-beat heart rate and QT variability such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the severity of withdrawal symptoms and with serum electrolyte concentrations. RESULTS: Heart rate and QTvi were significantly increased in acute alcohol withdrawal. Abstained alcoholics did not significantly differ from controls. While QTvi correlated with the severity of alcohol withdrawal symptoms, the mean QT interval duration showed an inverse relationship with serum potassium concentrations. CONCLUSION: Our data indicate increased QT variability and thus increased repolarization lability in acute alcohol withdrawal. This might add to the elevated risk for serious cardiac arrhythmias. In part, these changes might be related to increased cardiac sympathetic activity or low potassium, thus suggesting the latter as possible targets for adjuvant pharmacological therapy during withdrawal. PMID- 17350181 TI - Customizing treatment to the patient: adaptive treatment strategies. PMID- 17350182 TI - Identification and transcription of transfer RNA genes in dinoflagellate plastid minicircles. AB - The dinoflagellate chloroplast genome is unique in that the genes are found on small circular DNA molecules carrying from one to three genes. In addition, only 14 of the typical chloroplast-located genes have so far been discovered on minicircles, while a number have been transferred to the nucleus. We have sequenced four new minicircles from the dinoflagellate Heterocapsa triquetra, three of which carry a single protein-coding gene (psbD, psbE, petD) and one that appears to be an "empty" circle. Using the tRNA prediction programs ARAGORN and tRNAscan-SE, tRNA-Met was found in the petD circle immediately downstream of the end of petD, while tRNA-Trp and tRNA-Pro were detected in the psbE and petD circles as well as in several chimeric circles of H. triquetra and the psbA minicircles of Heterocapsa pygmaea. RT-PCR showed that the tRNAs were co transcribed with the protein-coding genes that preceded them, and cleaved from the precursor before a poly(U) tail was added to the mRNA. PMID- 17350183 TI - Characterization of biosynthetic gene cluster for the production of virginiamycin M, a streptogramin type A antibiotic, in Streptomyces virginiae. AB - Virginiamycin M (VM) of Streptomyces virginiae is a hybrid polyketide-peptide antibiotic with peptide antibiotic virginiamycin S (VS) as its synergistic counterpart. VM and VS belong to the Streptogramin family, which is characterized by strong synergistic antibacterial activity, and their water-soluble derivatives are a new therapeutic option for combating vancomycin-resistant Gram-positive bacteria. Here, the VM biosynthetic gene cluster was isolated from S. virginiae in the 62-kb region located in the vicinity of the regulatory island for virginiamycin production. Sequence analysis revealed that the region consists of 19 complete open reading frames (ORFs) and one C-terminally truncated ORF, encoding hybrid polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS), typical PKS, enzymes synthesizing precursors for VM, transporters for resistance, regulatory proteins, and auxiliary enzymes. The involvement of the cloned gene cluster in VM biosynthesis was confirmed by gene disruption of virA encoding a hybrid PKS-NRPS megasynthetase, which resulted in complete loss of VM production without any effect on VS production. To assemble the VM core structure, VirA, VirF, VirG, and VirH consisting, as a whole, of 24 domains in 8 PKS modules and 7 domains in 2 NRPS modules were predicted to act as an acyltransferase (AT)-less hybrid PKS-NRPS, whereas VirB, VirC, VirD, and VirE are likely to be essential for the incorporation of the methyl group into the VM framework by a HMG-CoA synthase-based reaction. Among several uncommon features of gene organization in the VM gene cluster, the lack of AT domain in every PKS module and the presence of a discrete AT encoded by virI are notable. AT-overexpression by an additional copy of virI driven by ermEp() resulted in 1.5-fold increase of VM production, suggesting that the amount of VirI is partly limiting VM biosynthesis. PMID- 17350184 TI - Molecular cloning and characterization of a novel form of the human vacuolar H+ ATPase e-subunit: an essential proton pump component. AB - Several of the 13 subunits comprising mammalian H(+)-ATPases have multiple alternative forms, encoded by separate genes and with differing tissue expression patterns. These may play an important role in the intracellular localization and activity of H(+)-ATPases. Here we report the cloning of a previously uncharacterized human gene, ATP6V0E2, encoding a novel H(+)-ATPase e-subunit designated e2. We demonstrate that in contrast to the ubiquitously expressed gene encoding the e1 subunit (previously called e), this novel gene is expressed in a more restricted tissue distribution, particularly kidney and brain. We show by complementation studies in a yeast strain deficient for the ortholog of this subunit, that either form of the e-subunit is essential for proper proton pump function. The identification of this novel form of the e-subunit lends further support to the hypothesis that subunit differences may play a key role in the structure, site and function of H(+)-ATPases within the cell. PMID- 17350186 TI - Identification and purification of a novel adhesion-associated protein in a new strain of Lactobacillus, L15, from flounder (Paralichthys olivaceus). AB - Adhesion is a crucial and prerequisite step for Lactobacillus colonization in the digestive tract which subsequently confers its probiotic effects on the host. The aim of this report was to identify and purify a novel adhesion-associated protein which mediates the adherence of a new strain of Lactobacillus, L15, to intestinal mucus from flounder. It was shown that surface proteins were involved in the adhesion of L15 to flounder mucus. The adhesion efficiencies of this strain were significantly decreased from 16.0% to 5.8% after extraction of L15 with 5 M LiCl and were further inhibited to 3.6% by blocking with an L15 cell extract containing surface proteins. The adhesion-associated protein in the cell extract was visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) and was identified by Western blotting with sulfo-N-hydroxysuccinimide biotin (B-NHS)-labeled crude mucus as a 61.8 kDa protein. The identical protein could be purified from L15 whole cell proteins by affinity chromatography using Sepharose, covalently coupled with crude mucus. It was demonstrated that the adhesion-associated protein was a new adhesive protein. Its characteristics and similarities with other known adhesive proteins need further investigation. PMID- 17350185 TI - TNF-alpha represses transcription of human Bone Morphogenetic Protein-4 in lung epithelial cells. AB - Bone Morphogenetic Proteins are key signaling molecules in vertebrate development. Little is known about Bmp gene regulation in any organ. In Drosophila, the Bmp gene, dpp is regulated by Dorsal, the invertebrate homologue of Rel-NF-kB. In this study we examined whether TNF-alpha, which activates NF-kB, can regulate Bmp4 gene expression. TNF-alpha reduced Bmp4 mRNA in lung adenocarcinoma A549 cells and repressed transcriptional activity of the human Bmp4 promoter in a dose-dependent manner. Similar repression was observed when the Bmp4 promoter was co-transfected with a p65 (RelA) expression vector in the absence of TNF-alpha treatment, suggesting that RelA mediates the effect of TNF alpha. In support of this finding, the repressor effect of TNF-alpha on Bmp4 was abrogated by a co-transfected dominant negative mutant of IkB (S32A/S36A). The human Bmp4 promoter contains 3 putative consensus binding sites for NF-kB. Surprisingly, only one of the latter binding sites was capable of binding NF-kB. Repressor effect of NF-kB was not dependent on any of the three binding sites, but localized to a 122 bp fragment which bound both RelA and SP1. SP1 stimulated transcription, whereas increasing doses of RelA opposed this effect. In vivo, TNF alpha inhibited branching morphogenesis and LacZ gene expression in Bmp4-lacz transgenic lungs. These data support a model in which TNF-alpha-induced RelA interacts with SP1 to bring about transcriptional repression of Bmp4 gene. These findings provide a mechanistic paradigm for interactions between mediators of inflammation and morphogenesis with relevant implications for normal lung development and pathogenesis of disease. PMID- 17350187 TI - Ethanol and acetaldehyde induce similar changes in extracellular levels of glutamate, taurine and GABA in rat anterior cingulate cortex. AB - It is controversial regarding to the roles of acetaldehyde and ethanol in the central nervous system. In the present study, the effects of acetaldehyde and ethanol on extracellular levels of glutamate, taurine and GABA in the anterior cingulate cortex (ACC) of freely moving rats were investigated by using the microdialysis technique coupled to high performance liquid chromatography (HPLC) with fluorescent detection. The result showed that glutamate levels were significantly decreased after acute administration of acetaldehyde (AcH, 20 and 100 mg/kg, i.p.), while taurine levels were significantly increased after the higher dose of acetaldehyde (100 mg/kg, i.p.). GABA levels had no changes at any doses of acetaldehyde tested. Interestingly, similar changes of these amino acids were induced by ethanol (EtOH, 3 g/kg, i.p.) when sodium azide (NaN3, 10 mg/kg, i.p.), a catalase inhibitor that can reduce brain ethanol metabolism, was used simultaneously. These findings suggest that acetaldehyde and ethanol have the similar effects on the extracellular output of glutamate, taurine and GABA in the ACC. PMID- 17350188 TI - Effect of individual heifer oocyte donors on cloned embryo development in vitro. AB - The aim of this study was to determine the effect of individual oocyte donors on cloned embryo development in vitro. Five Holstein heifers of varied genetic origins were subject to ovum pick up (OPU) once weekly. In total, 913 oocytes were recovered from 1304 follicles. A mean of 7.7+/-0.4 oocytes was recovered per session per animal. Individual mean oocyte production varied significantly in quantity but not in quality (morphological categories) among heifers. Oocytes from individual heifers were used as recipient cytoplasm for somatic cell nuclear transfer (SCNT). Cumulus cells, collected from a single Holstein cow genetically unrelated to the oocyte donor, were used as donor cells. Although the percentage of reconstructed embryos that started to cleave was nearly constant, the percentage of cleaved embryos that developed into blastocysts showed clear individual heifer variation (61%, 51%, 31%, 28% and 24%, respectively), with a mean of 38% showing blastocyst formation. In vitro fertilization (IVF) was also conducted with oocyte from the same heifers used in SCNT. A variation of blastocyst production among individual heifers was also shown in the IVF experiment, but the rank of oocyte donor based on the blastocyst rate was changed. In conclusion, individual oocyte donor may have an effect on cloned embryo development in vitro, which differed from the effect on IVF embryos. PMID- 17350189 TI - Systemic and intraovarian effects of corpus luteum on follicular dynamics during estrous cycle in hair breed sheep. AB - The present study aimed to determine systemic and local effects of corpora lutea (CL), on follicular dynamics throughout the estrous cycle. All follicles >or=2 mm and CL were assessed by daily transrectal ultrasonography in 12 West African ewes. Blood samples were collected to determine plasma concentration of progesterone. Fifteen estrous cycles were evaluated with a mean interovulatory interval of 16.8+/-0.2 days. Two (13.3%), 10 (66.7%) and 3 (20%) of the estrous cycles had 2, 3 and 4 waves of follicular development, respectively. In sheep with three waves of follicular development, both the length of growing phase and the growth rate of dominant follicles from midluteal wave II were diminished (3.4+/-0.3 days, P<0.0001, and 0.4+/-0.1 mm/day, P<0.01, respectively) when compared to follicles from early luteal phase (wave I, 4.1+/-0.2 days, and 0.7+/ 0.1 mm/day) or late luteal phase (wave III, 6.3+/-0.4 mm and 0.6+/-0.1 mm/day). The diameter of the dominant follicle was smaller during the midluteal phase (3.9+/-0.1 mm, P<0.0001) than in the early and late luteal phase (5.0+/-0.2 and 5.7+/-0.2 mm; respectively). The effect of the dominant follicle was less during midluteal phase, because number of accompanying smaller follicles was fewer (P<0.01) in waves I and III (6.3+/-0.9 compared with 3.4+/-0.8 and 2.3+/-0.7). The number of follicles was also different between ovaries that had CL and those that did not. The total number of large follicles during the luteal phase was less in ovaries with CL (0.9+/-0.5 compared with 2.7+/-0.3; P<0.01), as was the mean daily number of both large (0.1+/-0.02 compared with 0.2+/-0.02; P<0.001) and total number of follicles >or=2 mm (2.5+/-0.1 compared with 3.3+/-0.1; P<0.01). Current results indicate that the presence of a functional CL may exert both systemic and local effects on the population of follicles, affecting the dominance exerted by large follicles. PMID- 17350190 TI - The longitudinal effects of a perimenopausal health education intervention on the mid-life women in Taiwan. AB - OBJECTIVES: The study purpose was to evaluate the longitudinal effects, after 3 months and 1-year, of a perimenopausal health education intervention for mid-life women in Taiwan. METHODS: This study was conducted at two hospitals and their neighborhood communities (each included three subgroups, traditional Chinese, gynecologic and neighborhood communities), using a parallel-design, control trial for mid-life women. There were three instruments: (1) the Perceived Uncertainty Scale, (2) the Perceived Perimenopausal Disturbances Scale and (3) the Practice of Health Behaviors Scale. The intervention effects from the study baseline to a 1-year follow-up were estimated using the mixed effect model (SAS-MIXED procedure) for repeated measures of health behaviors, perceived uncertainty and perceived perimenopausal disturbances. RESULTS: A total of 161 women were in the education group, while 174 women were in the control group. After a 1-year follow up, health education intervention had significantly increased the practice of health behavior in both Chinese medicine subgroups (beta=15.39, P<0.001) and gynecologic clinics subgroup (beta=10.08, P<0.005). On the other hand, health education intervention had significantly decreased perceived uncertainty in subgroups of Chinese medicine (beta=-9.52, P<0.005). CONCLUSIONS: The perimenopausal health education had positive effects in reducing perceived uncertainty and increasing practice of health behavior among women from Chinese medicine clinics after a 1-year follow-up. Women from the gynecologic clinics showed the intervention effects of increasing health behavior after a three month and 1-year follow-ups. However, the women from neighborhood communities did not show any significant intervention effects at follow-ups. It is important to urge the women from communities to promote health practices for their perimenopausal transition instead of just living with their changing health. PMID- 17350191 TI - Stabilization mechanism of limaprost in solid dosage form. AB - The effect of polymeric pharmaceutical excipients on the degradation of limaprost by hydrolysis was assessed by near infrared (NIR) spectroscopy and spin-spin relaxation time (T(2)) measurements of proton NMR. Freeze-dried limaprost-alfadex formulated with various polymeric pharmaceutical excipients was exposed under humidified condition at 25 degrees C and 75% relative humidity. The freeze-dried limaprost-alfadex formulated with cellulose derivatives, hydroxypropylmethylcellulose (HPMC) and hydroxypropylcellulose (HPC-L), degraded easily. However, degradation was suppressed in samples formulated with polysaccharides, dextran40, dextrin, and pullulan, although the water sorption was more than 10% (w/w). A second-derivative NIR study showed the changes in the water mobility in the mixtures. The absorption peak near 1900nm, which was assigned to water with high mobility, was observed in the humidified HPMC and HPC L. The proton NMR spin-spin relaxation time measurements indicated that the structural relaxation of a polymeric excipient changed upon humidification. The polysaccharides showed only Gaussian relaxations, but the cellulose derivatives showed Lorentzian relaxations and Gaussian relaxations. The T(2) values of the Gaussian relaxation in HPMC and HPC-L were higher than those in dextran40, dextrin, and pullulan throughout the humidifying period. The higher molecular mobility of HPMC and HPC-L is related to the mobility of water, which may accelerate limaprost degradation. PMID- 17350192 TI - Toxicological evaluation of ethyl acetate extract of Cylicodiscus gabunensis stem bark (Mimosaceae). AB - The toxicity profile of the ethyl acetate (EA) extract of the stem bark of Cylicodiscus gabunensis (CG) was studied in Wistar rats. The rats were administered graded doses (0.75, 1.5, 3 and 6 g/kg p.o.) of the extract daily for 6 weeks and the effects on clinical signs, body weight, food and water consumption, organ weight, haematology, histology as well as serum, hepatic and renal biochemical parameters were measured. Body weight of dosed and control rats increase throughout the duration of treatment but food and water consumption were not significantly affected. The relative weights of the liver, lungs, heart and kidneys remained normal whereas a significant change was observed in that of the spleen. The hematocrit level was increased in treated animal. Our data demonstrates a significant increase in serum concentrations of aspartate amino transferase, alanine amino-transferase, total cholesterol and glucose with high dose of CG treatment tested (3-6 g/kg). CG also caused a significant reduction in hepatic malondialdehyde concentration. Renal urea and creatinine levels were reduced significantly in test groups. Histological findings reveal a characteristic progression treatment-related effect on liver, kidneys and lungs. The acute toxicity LD50 was estimated at 14.5 and 11 g/kg body weight (b.w.) for male and female respectively, but dose-related mortality of 30 and 50% were observed during the sub-acute toxicity. These findings have once more highlighted the limitations of the acute toxicity LD50 testing and suggest that CG may exert varied toxicological effects when administered orally in rats. PMID- 17350193 TI - Antinociceptive activity of aqueous extract of Pachyptera hymenaea (DC.) in mice. AB - The standardized aqueous extract of leaves of Pachyptera hymenaea (DC.) belonging to family Bignoniaceae was investigated for possible antinociceptive effect in mice. Three different models were used to study the effects of extract on nociception, namely acetic acid-induced writhing test, formalin test (paw licking test) and tail flick test in mice. The extract was administered 1h prior to pain induction in the dose range of 25, 50 and 75mg/kg orally. The extract at the given dose range reduced the acetic acid induced nociception by 44.03, 52.90 and 62.46% respectively. The extract reduced formalin effect in both the phases of experiment by 32.36, 41.94, 54.29% and 35.39, 50.17, 55.86% respectively. In the tail flick study, animals' reaction time were increased by 22.69, 38.24 and 40.26% at the above selected doses respectively at 120min after drug administration. Naloxone (2mg/kg; s.c.) significantly antagonized the effect of extract in formalin and tail flick method, while partially antagonized the effect in writhing test. However caffeine completely reverted the extract effect in both the phases of formalin test. Results of these studies revealed that the extract have significant antinociceptive activity in the used models with a possible involvement of central mechanism and adenosine system. PMID- 17350194 TI - Antinociceptive and anti-inflammatory properties from the bulbs of Cipura paludosa Aubl. AB - This study examined the antinociceptive and anti-inflammatory actions of Cipura paludosa Aubl. in several models of inflammatory pain in mice and rats. The ethanolic extract (EE) from Cipura paludosa (1-300mg/kg) given by i.p. and p.o. routes, 30 or 60min earlier, produced a dose-dependent inhibition of the acetic acid-induced pain and Evans blue leakage in mice with ID(50) values of 2.8 and 17.6mg/kg and 17.2 and 176.1mg/kg, respectively. The EE (10mg/kg, i.p.) also inhibited the allodynia (39+/-6%)- and oedema (97+/-6%)-induced by the intraplantar injection of CFA. In addition, the EE (1-30mg/kg, i.p.) inhibited both mechanical and thermal hyperalgesia induced by prostaglandin E(2), PMA and bradykinin in the rat paw, with ID(50) values of 7.3, 12.1 and 4.7 and 13.9, 18.9 and 1.5mg/kg, respectively. These data demonstrate that EE of Cipura paludosa elicited pronounced antinociceptive and anti-inflammatory actions against some models of inflammatory pain in mice and rats. The mechanism by which the extract produced antinociception still remains unclear, but a great part of this effect seems to be related to modulation of the release or action of pro-inflammatory mediators. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant. PMID- 17350195 TI - Ligustilide attenuates pain behavior induced by acetic acid or formalin. AB - Danggui is a popular traditional Chinese medicinal (TCM) herb, which has long been used clinically to treat primary dysmenorrhoea. In a recent study, we demonstrated that ligustilide (LIG), one of the main compounds of Danggui essential oil, has multiple effects on uterine smooth muscles and possesses a non specific antispasmodic function, which suggests that LIG might play a major role in the therapeutic activity of Danggui in primary dysmenorrhoea. Since pain is the main syndrome of dysmenorrhea, the present investigation was carried out to evaluate the analgesic activity of LIG in vivo. LIG was intra-gastrically administered to animals. We demonstrated for the first time that LIG could cause a significant dose-related reduction of acetic acid-induced writhing response and formalin-induced licking time in both the early and late phases. These results showed that LIG possessed antinociceptive and anti-inflammatory activities. These findings plus the data we reported recently implied that LIG not only has an active dilatory effect on myometrium but also an effective role in reducing the neurogenic and inflammatory pain, thus having the potential to be developed into an effective drug for the treatment of various pain syndromes including primary dysmenorrhoea. PMID- 17350196 TI - A red clover (Trifolium pratense) phase II clinical extract possesses opiate activity. AB - Trifolium pratense (TP) is one of the most common herbs for the relief of menopausal symptoms. Little is known about its mechanisms of action. In this study, we investigated the affinity of TP at the mu- and delta-opiate receptors. We found that a clinically used TP extract bound to the mu-opiate receptor with a high affinity (K(i)=9.7+/-1.6microg/ml). The same extract was also found to have affinity at the delta-opiate receptor with K(i) of 15.9+/-2.4microg/ml. These results for the first time suggest a potential new mechanism of action of TP at the opiate receptors. Given the essential role of the opioid system in regulating temperature, mood, and hormonal levels and actions, this may explain in part the beneficial effect of TP in alleviating menopausal symptoms. PMID- 17350197 TI - Fatal unintentional intoxications with tramadol during 1995-2005. AB - Tramadol is an extensively used centrally acting analgesic and is considered a safe drug devoid of many serious adverse effects of traditional opioids. However, recently, toxicity and an abuse potential of tramadol have been reported. This study examined fatal unintentional tramadol intoxications among Swedish forensic autopsy cases between 1995 and 2005. All fatal intoxications were selected, in which toxic concentrations of tramadol (>1 microg/g femoral blood) had been detected, and where the forensic pathologist considered the intoxication unintentional and the fatal outcome at least partly explained by tramadol. Toxicology analyses, police reports, autopsy protocols and medical records were scrutinized. A total of 17 cases (eleven men and six women) of fatal unintentional tramadol intoxications were identified. For these cases the median age was 44 years (range 18-78 years) and the median tramadol concentration was 2.0 microg/g (range 1.1-12.0 microg/g). Other pharmaceutical substances, illicit drugs or ethanol were detected in addition to tramadol in all of these cases. In fact, intoxication with multiple drugs was considered the cause of death in 10 (59%) cases. However, in seven cases tramadol was the only substance present in toxic concentrations. A history of substance abuse was identified in 14 (82%) subjects and a present tramadol abuse in 8 (47%). These results suggest that fatal intoxications with tramadol may occur unintentionally and that subjects with a history of substance abuse may be at certain risk. Precaution is therefore warranted when prescribing tramadol in such patients. PMID- 17350198 TI - Early diagnosis of Wegener's granulomatosis presenting with bilateral facial paralysis and bilateral serous otitis media. AB - Wegener's granulomatosis (WG) is a multi-system disease characterized by granuloma formation and widespread necrotizing vasculitis. It classically presents with involvement of the upper and lower respiratory tracts and renal system. Facial nerve palsy and otologic manifestations have been reported during the course of the disease but it is extremely rare as the presenting features. In Literature only one case of bilateral facial palsy as presenting sign of WG is reported. The testing of anticytoplasmic antibodies versus neutrophil polymorphonucleate granules (c-ANCA) are highly specific for the diagnosis of WG, being positive in 97% of the cases. The early diagnosis and the timely medical treatment lead to high rates of remission of an otherwise lethal disease. A case of WG presenting with bilateral facial paralysis and bilateral serous otitis media is reported. PMID- 17350199 TI - [Neurologic and psychiatric manifestations of Lyme disease]. AB - The neurological and psychiatric manifestations of Borrelia burgdorferi sensu lato are so numerous that Borrelia is also called the "new great imitator". Thus knowing about the multiple clinical aspects of neuroborreliosis is necessary for the clinician. We reviewed literature for "classical" neuroborreliosis such as acute meningoradiculitis or chronicle encephalomyelitis, but also for encephalitis, myelitis, polyneuritis, radiculitis and more controversial disorders such as chronic neurological disorders, ischemic and hemorrhagic stroke, and motor neuron disease. We specified every time on which basis each disorder was attributed to Lyme disease, particularly if European or American criteria were met. Every part of the nervous system can be involved: from central to peripheral nervous system, and even muscles. In endemic areas, Lyme serology must be assessed in case of unexplained neurological or psychiatric disorder. In case of positive serology, CSF assessment with intrathecal anti-Borrelia antibody index will be more efficient to prove the diagnosis. PMID- 17350200 TI - Positioning of the wrist for scaphoid radiography. AB - PURPOSE: The purpose of this cadaver study was to determine the ideal position of the wrist for scaphoid radiography. MATERIALS AND METHODS: Four cadaver wrists were rotated around their longitudinal axis in 15 degrees increments and exposures were taken. Seven postero-anterior images were taken as well. Thus, 18 images of each wrist were available for assessment. Views were determined in which the main anatomic regions of the scaphoid were visualized undistorted. The size and localization of the overlap of other carpal bones were also evaluated. Finally, views with the best visualization of anatomic landmarks were selected. The results of these three investigations were compared to literature data. RESULTS: We consider the following four images the most valuable in the diagnostic imaging of scaphoid bone: (1) Postero-anterior view in ulnar deviation of wrist and fist position of the hand; (2) oblique view in 60 degrees of pronation; (3) oblique view in 60 degrees of supination; (4) lateral view. CONCLUSION: We concluded that our four views are sufficient for proper radiographic evaluation of the scaphoid. PMID- 17350201 TI - Salvage treatment of pneumonia and initial treatment of tracheobronchitis caused by multidrug-resistant Gram-negative bacilli with inhaled polymyxin B. AB - Systemic colistin has shown efficacy against multidrug-resistant Pseudomonas aeruginosa and Acinetobacter spp., but it has presented poor results in pneumonia. Aerosolized polymyxin in cystic fibrosis patients has had good results. In this study, inhaled polymyxin B was used to treat respiratory infections by multidrug-resistant Gram-negative bacilli (MR-GNBs). Nineteen patients were treated with inhaled polymyxin B: 14 pneumonia, most of which had previously failed treatment with intravenous polymyxin B, and 5 tracheobronchitis. Inhaled polymyxin B was given at the dose of 500,000 IU twice a day after an aerosolized beta(2)-agonist. In pneumonia, inhaled and intravenous polymyxin B was given together. Median age was 69 years; 89% were in the intensive care unit. Sixteen infections (84%) were caused by P. aeruginosa. Klebsiella pneumoniae, Alcaligenes xylosoxidans, and Burkholderia sp. caused one infection each. In the 14 pneumonia cases, median of previous use of intravenous polymyxin B was 20 days (range, 0-32). Inhaled polymyxin B was used for a mean of 14 days (range, 4-25). Cure occurred in 10 (53%) patients, improvement in 8 (42%), and failure in 1. Nine patients died during hospitalization (all with pneumonia). Adverse events occurred in 4 patients without interruption of inhalation. This is the largest report using inhaled polymyxin B to treat nosocomial pneumonia by MR-GNB that had failed intravenous polymyxin B. It was also effective alone in P. aeruginosa tracheobronchitis. PMID- 17350202 TI - Burkholderia pseudomallei animal and human isolates from Malaysia exhibit different phenotypic characteristics. AB - Burkholderia pseudomallei is a Gram-negative saprophytic soil bacterium, which is the etiologic agent of melioidosis, a severe and fatal infectious disease occurring in human and animals. Distinct clinical and animal isolates have been shown to exhibit differences in phenotypic trait such as growth rate, colony morphology, antimicrobial resistance, and virulence. This study was carried out to gain insight into the intrinsic differences between 4 clinical and 6 animal B. pseudomallei isolates from Malaysia. The 16S rRNA-encoding genes from these 10 isolates of B. pseudomallei were sequenced to confirm the identity of these isolates along with the avirulent Burkholderia thailandensis. The nucleotide sequences indicated that the 16S rRNA-encoding genes among the 10 B. pseudomallei isolates were identical to each other. However, the nucleotide sequence differences in the 16S rRNA-encoding genes appeared to be B. pseudomallei and B. thailandensis specific. The growth rate of all B. pseudomallei isolates was determined by generating growth curves at 37 degrees C for 72 h. The isolates were found to differ in growth rates with doubling time varying from 1.5 to 2.3 h. In addition, the B. pseudomallei isolates exhibited considerable variation in colony morphology when grown on Ashdown media, brain-heart infusion agar, and Luria-Bertani agar over 9 days of observation. Antimicrobial susceptibility tests indicated that 80% of the isolates examined were Amp(R) Cb(R) Kn(R) Gm(R) Chl(S) Te(S). Virulence of the B. pseudomallei clinical and animal isolates was evaluated in B. pseudomallei-susceptible BALB/c mice. Most of the clinical isolates were highly virulent. However, virulence did not correlate with isolate origin since 2 of the animal isolates were also highly virulent. PMID- 17350203 TI - Rapid detection of early typhoid fever in endemic community children by the TUBEX O9-antibody test. AB - Typhoid remains a global public health problem, and quick accurate immunodiagnosis is needed. Here, we examined the performance of the 5-min TUBEX O9-antibody detection kit in 243 outpatients (mostly children and infants) in their first week of fever and 57 healthy subjects in the Bangladesh community. Based on culture results, TUBEX was 91.2% (31/34) sensitive and 82.3% (172/209) specific in febrile subjects. However, specificity was better in nonfebrile healthy subjects (89.5%, 51/57) or in febrile individuals who serologically had dengue fever (90.5%, 57/63), suggesting that some culture-negative febrile individuals could be truly typhoidal. These individuals were also positive in an anti-crude O9 enzyme-linked immunosorbent assay (ELISA) and the Widal test. Regression analysis of the TUBEX and ELISA results showed good concordance between them, better with the combined IgM-IgG ELISA than with IgM alone, suggesting that TUBEX detects IgM antibodies not necessarily by themselves, as previously reported, but with the help of IgG antibodies. PMID- 17350204 TI - Rapid detection of rifampin-resistant Mycobacterium tuberculosis directly from stained sputum smears using single-tube nested polymerase chain reaction deoxyribonucleic acid sequencing. AB - Microscopy is the mainstay of laboratory diagnosis of tuberculosis especially in resource poor countries. The World Health Organization has also recommended microscopy as the mainstay of diagnosis for directly observed treatment, short course. Using DNA extracts from Ziehl-Neelsen (ZN)-stained sputum smears, a single-tube nested polymerase chain reaction was optimized to confirm Mycobacterium tuberculosis complex and detect rifampin (RIF) resistance by sequencing, using a combination of novel (rpoB47 and rpoB158) and previously described (rpoB105 and rpoB293) primers. Carryover DNA was strictly monitored using several negative controls, and inhibition was ruled out by spiked controls. No such target was detected from negative controls and purified genomic DNA from other nontubercular mycobacteria. Resistance could be detected in 91.1% (51/56) slides. The results obtained were concordant with the 1% proportion method and DNA sequencing performed on culture isolates. Our results demonstrate that the method is suitable for rapid detection of susceptibility to RIF in acid-fast bacillus-positive ZN-stained slides obtained from patients suspected of harboring drug-resistant M. tuberculosis. PMID- 17350205 TI - Incidence, risk factors, and predictors of outcome of candidemia. Survey in 2 Italian university hospitals. AB - In recent decades, Candida spp. emerged as the fourth most common cause of nosocomial bloodstream infections. The incidence of candidemia was 0.13 per 100 persons. Eighty-three cases (61%) of candidemia were due to Candida albicans and 53 (39%) to nonalbicans Candida spp. Twelve strains of Candida (9%) had shown in vitro resistance to fluconazole, 5 (4%) to itraconazole, 2 (1.5%) to voriconazole, 12 (9%) to 5-flucytosine, and 1 (0.7%) to amphotericin B. Multivariate logistic regression analysis of risk factors showed that length of hospitalization, presence of a central venous catheter, previous episodes of candidemia or bacteremia, parenteral nutrition, and chronic renal failure were variables independently associated with the development of candidemia. Multivariate logistic regression analysis of prognostic indicators showed that the independent variables associated with poor prognosis were inadequate initial therapy (P < .001) and high APACHE III score (P = .004). The inadequate initial therapy associated with mortality indicates the need for additional investigations to define high-risk patients for beneficial antifungal prophylaxis. PMID- 17350206 TI - Reevaluation of current susceptibility breakpoints for Gram-negative rods based on pharmacodynamic assessment. AB - Although pharmacodynamic (PD) modeling is now being considered for decision support for susceptibility breakpoint determination against Gram-negative bacteria, these PD-derived breakpoints should be verified using a clinically applicable population of organisms. In this analysis, a 5000-patient Monte Carlo simulation was used to determine PD breakpoints, the highest 2-fold MIC in which the probability of bactericidal target attainment (PTA) remained > or = 90%. Percent susceptibilities for 639 Pseudomonas aeruginosa, 103 Acinetobacter baumannii, 705 Escherichia coli, and 418 Klebsiella spp. collected during the 2004 Meropenem Yearly Susceptibility Test Information Collection surveillance study were then defined according to the PD-derived breakpoint (%S(PD)) and compared with the current Clinical Laboratory Standards Institute (CLSI)-defined breakpoints (%S(CLSI)). %S(PD) and %S(CLSI) were compared with the bactericidal PTA for each pathogen population to determine the degree of agreement. Resulting PD breakpoints were drug and dose dependent; moreover, values were commonly 2 to 4 MIC dilutions lower than CLSI breakpoints. Overall, %S(PD) more closely agreed with the PTA for the tested beta-lactam and fluoroquinolone dosing regimens. In contrast, %S(CLSI) overestimated PTA for many dosing regimens, especially against Pseudomonas: piperacillin/tazobactam 4.5 g qid (+9.7%), ciprofloxacin 0.4 g bid (+13.7%) and 0.4 g tid (+9.3%), and levofloxacin 0.5 g every 24 h (+22.4%) and 0.75 g every 24 h (+9.9%). Differences were most pronounced against the nonfermenting Gram-negative bacteria and were not observed among the Enterobacteriaceae. As a result, a new method of breakpoint classification is proposed, which is dosing regimen and pathogen specific, and is designed to denote isolates as susceptible only if target bactericidal exposures are achievable with the dosing regimen selected. PMID- 17350207 TI - Optochin resistance in Streptococcus pneumoniae induced by frozen storage in glycerol. AB - Susceptibility to optochin is frequently the only test used to differentiate Streptococcus pneumoniae from other alpha-hemolytic streptococci isolated from clinical specimens. The current study shows that storage of S. pneumoniae isolates in tryptic soy broth containing 15% glycerol at -70 degrees C can lead to optochin resistance. This optochin resistance was sometimes reversible by growing the bacteria in broth. Optochin-susceptible and optochin-resistant variants of individual S. pneumoniae isolates have similar pulsed-field gel electrophoresis pattern. However, optochin-resistant S. pneumoniae isolates exhibit differences in ultrastructure compared with optochin-susceptible variants. This study demonstrates that the frozen storages of S. pneumoniae in glycerol may affect the optochin phenotype. Thus, this characteristic should not be the only one used for identification of S. pneumoniae after frozen storage of isolates. PMID- 17350208 TI - Characterization of the Western blotting IgG reactivity patterns in the clinical phases of acquired syphilis. AB - We standardized the Western blotting (WB) method for detecting Treponema pallidum IgG (Tp-IgG) antibodies in sera samples of patients with syphilis and correlated the reactivity profile of bands with the clinical phases of the disease. The WB Tp-IgG has 100% sensitivity and 99.5% specificity. The clinical phases of the disease were associated with the reactive bands from TpN15 to TpN47. Quantitative Venereal Disease Research Laboratories was used to assist the WB Tp-IgG analysis. In primary syphilis, the reaction intensity for the antigenic band TpN47 was usually more intense when compared with other clinical phase. In secondary and sometimes in early latent syphilis, antibodies reacted with high numbers of antigenic proteins of T. pallidum. In late latent syphilis, various bands became negative, but the TpN15 and TpN47 were reactive. In tertiary syphilis, we observed reactivity with the TpN15 band and low reactivity with the TpN47. We concluded that WB Tp-IgG could be used to confirm serologic tests and characterize clinical phases of syphilis. PMID- 17350209 TI - Rapid identification of Fusobacterium nucleatum and Fusobacterium necrophorum by fluorescence in situ hybridization. AB - Identification of clinically relevant Fusobacterium spp. is hampered by their slow growth, their frequent occurrence in polymicrobial culture, and the low reliability of biochemical differentiation methods. A newly developed fluorescence in situ hybridization (FISH) assay allowed reliable and rapid identification of Fusobacterium necrophorum and Fusobacterium nucleatum from culture. Preliminary results show that the method offers the perspective for direct detection of these pathogens in blood cultures and abscess aspirates. PMID- 17350210 TI - Relevance of autoantibody detection to the rapid diagnosis of brucellosis. AB - The rose bengal test is often used for rapid diagnosis of human brucellosis in endemic areas. However, autoantibodies have never been investigated as a reason for false-positive or false-negative results. Therefore, the aim of this study was to show the effect of autoantibody detection on the rapid diagnosis of human brucellosis in an endemic area. The study included 2 groups: antinuclear antibody (ANA)-positive and ANA-negative groups. Diagnosis of brucellosis was established by isolation of Brucella spp. from blood culture. The overall sensitivity and specificity of the rose bengal test were 100% and 90.8%, respectively. The specificity (100% versus 89%) and positive predictive value of the test (100% versus 8%) fell markedly from the ANA-negative to the ANA-positive group. As a conclusion, this study verified our suspicion about the effect of autoantibodies on rose bengal test results to the diagnosis of human brucellosis. However, to have definite decisions, extensive studies with larger populations are needed. PMID- 17350211 TI - Oesophagostomum dentatum: potential as a model for genomic studies of strongylid nematodes, with biotechnological prospects. AB - There are substantial gaps in the knowledge of the molecular processes of development and reproduction in parasitic nematodes, despite the fact that understanding such processes could lead to novel ways of treating and controlling parasitic diseases, through blocking or disrupting key biological pathways. Biotechnological advances through large-scale sequencing projects, approaches for the analysis of differential gene and protein expression and functional genomics (e.g., double-stranded RNA interference) now provide opportunities to investigate the molecular basis of developmental processes in some parasitic nematodes. The porcine nodule worm, Oesophagostomum dentatum (order Strongylida), may provide a platform for testing the function of genes from this and related nematodes, given that this species can be grown and maintained in culture in vitro for periods longer than other nematodes of the same order. In this article, we review relevant biological, biochemical and molecular biological and genomic information about O. dentatum and propose that the O. dentatum - pig system provides an attractive model for exploring molecular developmental and reproductive processes in strongylid nematodes, leading toward new intervention methods and biotechnological outcomes. PMID- 17350212 TI - Biodiesel from microalgae. AB - Continued use of petroleum sourced fuels is now widely recognized as unsustainable because of depleting supplies and the contribution of these fuels to the accumulation of carbon dioxide in the environment. Renewable, carbon neutral, transport fuels are necessary for environmental and economic sustainability. Biodiesel derived from oil crops is a potential renewable and carbon neutral alternative to petroleum fuels. Unfortunately, biodiesel from oil crops, waste cooking oil and animal fat cannot realistically satisfy even a small fraction of the existing demand for transport fuels. As demonstrated here, microalgae appear to be the only source of renewable biodiesel that is capable of meeting the global demand for transport fuels. Like plants, microalgae use sunlight to produce oils but they do so more efficiently than crop plants. Oil productivity of many microalgae greatly exceeds the oil productivity of the best producing oil crops. Approaches for making microalgal biodiesel economically competitive with petrodiesel are discussed. PMID- 17350213 TI - Postnatal development of GABA and calbindin cells and fibers in the prefrontal cortex and basolateral amygdala of gerbils (Meriones unguiculatus). AB - The postnatal maturation of immunohistochemically stained gamma-amino-butyric acid (GABA) and calbindin (CB) cells and fibers were quantitatively examined in the prefrontal cortex (PFC) and the basolateral amygdala (BLA) of the Mongolian gerbil (Meriones unguiculatus). Animals of different ages, ranging from juvenile (postnatal day (PD)14, PD20, PD30), to adolescent (PD70), adult (PD180, PD540) and aged (PD720) were analyzed. Results reveal an increase in GABAergic fiber densities between PD14-20 in the PFC and the BLA with a concomitant decrease in cell density. After PD70 GABA fiber density slightly decreases again in the BLA, while there is a further slow but significant increase in the PFC between PD70 and PD540. Fibers immunoreactive for the calcium binding-protein CB, which is predominantly localized in particular GABAergic subpopulations, also accumulate between PD14 and PD20 in the PFC and BLA, while a concomitant decrease in cell density is only seen in the BLA. Both areas reveal a decrease of CB cells between PD30 and PD70, which parallels with a decrease of CB fibers in the PFC. However, there is no particular 'aging-effect' in the fiber or cell densities of GABA or CB in any of the investigated areas in old animals. In conclusion, we here demonstrate long-term dynamics in cell and fiber densities of the GABAergic system until late in development which might correspond to the prolonged maturation of other neuroanatomical and functional systems. PMID- 17350214 TI - Measuring shared decision making processes in psychiatry: skills versus patient satisfaction. AB - OBJECTIVE: To measure to what extent clinicians in a psychiatry department involve patients in decision making about treatment choice and to compare these data with patients' satisfaction rates about clinician communication behaviours. METHODS: Communication was analyzed by scoring 61 audio taped consultations with a validated instrument (OPTION). Patients scored satisfaction on the same OPTION behaviours. Eight clinicians were involved, as were 61 patients. RESULTS: The clinicians scored on average 43 points at overall 'shared decision making', on a scale of 0-100. Clinicians performed well in asking if patients had any questions. They scored low on meta-items about the decision making process: checking the preferred approach of the patient to receive information, or checking the preferred level of involvement in decision making. Satisfaction scores of a group of 29 patients showed no concern about these low scores. CONCLUSION: The clinicians in this study did not ask meta questions about participation in decision making. An explanation given was that they intuitively 'feel' if a patient wants to be involved or not. Patients did not express great concern about this. More experiments with clinicians openly checking desired participation levels of patients are needed, in order to learn more about possibilities in meta communication, and possible biases of clinicians. PRACTICE IMPLICATIONS: Our starting point was that clinicians need to become experts in all roles of their profession, as communicator as well as medical expert. Providing mirror information by assessing decision making behaviours will help to improve performance. Clinicians should be able to perform these SDM behaviours, even if patients are not asking for participation. Claims that clinicians do empathically feel if patients are able to involve in decision making, should be checked by scientific experiments. PMID- 17350215 TI - Anatomic exclusion from endovascular repair of thoracic aortic aneurysm. AB - OBJECTIVES: We sought to define the current anatomic barriers to thoracic aortic aneurysm (TAA) stent grafting to guide future device development. METHODS: All patients presenting with TAA requiring repair were evaluated for endovascular repair during a 4-year period (2000 to 2004). The TAAs evaluated were those beginning distal to the left common carotid artery (LCCA) and ending proximal to the celiac artery. All patients in whom endovascular repair was indicated underwent cross-sectional imaging by computed tomography angiography and three dimensional modeling of their thoracic and abdominal arterial anatomy. Patients were evaluated for endovascular TAA repair in the context of the inclusion/exclusion criteria of pivotal United States Food and Drug Administration trials of the Gore TAG and Medtronic Talent devices. Anatomic requirements included >or=20 mm of suitable proximal and distal neck length, and proximal and distal neck diameters of 20 to 42 mm. These trials allowed the use of femoral or iliac access, including the use of conduits, and permitted stent graft coverage of the left subclavian artery (LSA) after preliminary carotid subclavian bypass. Patients rejected for medical reasons or who died during evaluation were not included in the review. RESULTS: A total of 126 patients (73 men, 53 women) with TAA located between the LCCA and celiac artery were screened for endovascular repair, and 33 (26%) were rejected for anatomic reasons. The remaining 93 patients underwent endografting (59 Talent, 34 TAG). Rejection was not significantly different by gender (16/73 men, 17/53 women, P = .22, NS). Most patients (28/33) were rejected for more than one criterion. Hostile proximal neck characteristics were the most prevalent reason for disqualification, despite the ability to cover the LSA to extend the proximal seal zone. Many of these patients (16/28) also had distal neck anatomy unsuitable for grafting. Overall, 19 patients had hostile distal necks. Difficulties with vascular access (diseased or tortuous iliac arteries, or a small caliber aorta) that could not be overcome even by use of conduits occurred in a significant fraction of patients (10/33). CONCLUSIONS: Most patients with a TAA located between the LCCA and the celiac artery can be treated by endovascular repair. Patients excluded from TAA stent graft protocols for anatomic reasons most commonly have hostile proximal neck features that preclude endovascular repair with currently available devices. Transposition of arch vessels to facilitate greater use of existing stent grafts or development of new stent graft designs are needed to expand the applicability of TAA endovascular repair. PMID- 17350216 TI - Adjunctive parenteral therapy with lipo-ecraprost, a prostaglandin E1 analog, in patients with critical limb ischemia undergoing distal revascularization does not improve 6-month outcomes. AB - PURPOSE: In patients with critical limb ischemia (CLI), distal revascularization remains the procedure of choice for preventing limb loss, but long-term outcomes for pain relief, wound healing, and prevention of amputation remain suboptimal. Prostaglandin drug therapy as an adjuvant to revascularization may improve these outcomes. The current trial was designed to test the hypothesis that the use of lipo-ecraprost, a lipid encapsulated prostaglandin E(1) prodrug, as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI. METHODS: The study was randomized, multicenter, double blind, and placebo controlled. Patients meeting clinical and hemodynamic criteria for CLI who were undergoing either bypass or endovascular revascularization of the below knee popliteal or more distal arteries were randomized to receive placebo or a 60-microg dose of lipo-ecraprost administered intravenously starting or= 6 was considered successful treatment. Differences in leakage between responders and non responders, and between (169)Erbium and (186)Rhenium were examined. Regression analyses were performed to explore whether baseline variables predicted leakage. Both at 6 and 12 months response rates were 25 of 36 (69%). Five of 11 (45%) non responders showed leakage versus 20 of 25 (80%) responders (P=0.06). Mean leakage to lymph nodes was 0.4+/-0.7% versus 2.4+/-0.8% (P=0.04). Median leakage to liver/spleen was 0% versus 0.3% (P=0.4). Only age at the time of injection correlated significantly with leakage to lymph nodes. The (169)Erbium group showed leakage in 1 of 7 (14%) versus 24 of 30 (80%) for the (186)Rhenium group (P=0.002). Mean leakage to lymph nodes was 0.11+/-0.3% versus 2.1+/-2.8% (P=0.001). Median leakage to liver/spleen was 0% versus 0.5% (P=0.006). Leakage to non-target organs does not impair the clinical effect of RSO. Only age predicted leakage to lymph nodes significantly. Other baseline characteristics did not predict leakage. (169)Erbium shows significantly lower leakage to non target organs than (186)Rhenium in RSO. PMID- 17350270 TI - Dosimetry of (32)P radiocolloid for treatment of cystic craniopharyngioma. AB - In Tajrish Shohada Hospital, patients with either cystic craniopharyngiomas or cystic astrocytomas have been treated with (32)P radiocolloid by stereotactic procedure. The total activity was prescribed for delivery dose between 200 and 300 Gy to the cyst wall thicknesses of 1-3mm. In this project, MD-55-2 radiochromic film was utilized to determine the dose distribution around the source. The film dosimetry data were compared with Monte Carlo simulated values calculated with MCNP4C code. In addition, the clinical and dosimetric factors such as the cyst volume, and method of radiocolloid injection were evaluated. The required activity and distribution of radial dose in and out of cyst wall have been investigated. PMID- 17350271 TI - Effect of a commercial extract of Paullinia cupana (guarana) on the binding of 99mTc-DMSA on blood constituents: An in vivo study. AB - We studied the influence of a commercial extract of Paullinia cupana (guarana) on the binding of technetium-99m-dimercaptosuccinic acid ((99m)Tc-DMSA) on blood constituents. Plasma (P) and blood cells (BC) from Wistar rats (control and treated) were separated. P and BC were precipitated with trichloroacetic acid (TCA) or ammonium sulphate (AS) and soluble (SF) and insoluble fractions (IF) isolated. The percentage of incorporated radioactivity (%ATI) in each fraction was determined. The treatment influenced the %ATI in IF-P and in IF-BC isolated by TCA precipitation. PMID- 17350272 TI - Activity standardisation of (18)F and ionisation chamber calibration for nuclear medicine. AB - Primary activity standardisations were performed on solutions of (18)F using 4pibeta-gamma coincidence counting and liquid scintillation counting (LSC) according to the CIEMAT/NIST method. A beta(+)-emission probability of 96.86% was used for both methods. The various standardised (18)F solutions were measured in ionisation chambers of the Physikalisch-Technische Bundesanstalt (PTB) and compared by determining radionuclide calibration factors. Already in 2001 an (18)F solution had been standardised at the PTB and compared with the results of nine national metrology institutes (NMIs), using the ISOCAL IV secondary radionuclide calibrators of the National Physical Laboratory (NPL) as transfer instruments and a (68)Ge check source solution. These results were linked to the International Reference System (SIR) at the Bureau International des Poids et Mesures (BIPM) by aliquots of solutions sent by the Laboratoire National Henri Becquerel (BNM-LNHB) and the NPL. Further on, in 2005, PTB sent an aliquot of an (18)F solution to the SIR for ionisation chamber measurements. A value of the equivalent activity was determined and included in the key comparison database (KCDB). The recent PTB value of the equivalent activity of the SIR is in good agreement with the key comparison reference value determined from five NMIs. These results confirm that the standardisation of (18)F solutions can be achieved with the accuracy required for use in nuclear medicine and, in particular, for applications in positron emission tomography (PET). PMID- 17350273 TI - Investigation of photoneutron dose equivalent from high-energy photons in radiotherapy. AB - Spatial distribution of photoneutron dose equivalent during radiotherapy at different beam size, depth, and distance from a 15 MV linear accelerator was investigated with bubble detectors in a water phantom. The photoneutron dose equivalent was mainly from fast neutrons, and decreased with distance at a fixed field and with depth. Besides, photoneutron dose equivalent was slightly affected by beam size due to the variation of tungsten area exposed in the beam direction and photoneutrons occurred at the jaws. Fast photoneutron dose equivalent of shallow critical organs was represented still considerably outside the beam size. PMID- 17350274 TI - Use of (99m)Tc from a commercial (99)Mo/(99m)Tc generator as yield tracer for the determination of (99)Tc at low levels. AB - The concentrations of (99)Tc and impurity radionuclides in the (99m)Tc tracer solution obtained from a commercial (99)Mo/(99m)Tc generator were measured by gamma spectrometry and liquid scintillation counting. (99)Mo and (103)Ru were found in the (99m)Tc eluate. A simple separation using two extra alumina cartridges was investigated to purify the eluate to obtain a suitable (99m)Tc tracer with low (99)Tc concentration. The activity ratio of (99)Tc/(99m)Tc in the prepared (99m)Tc solution is lower than 15 x 10(-9), which is higher than the theoretical ratio of less than 10 x 10(-9). The possible reason is discussed. The (99)Tc in the 20 kBq spiked (99m)Tc tracer was found to be less than 0.3 mBq, which is lower than the detection limit of the radiometric method used for environmental samples. The purified (99m)Tc eluate is used as yield tracer for the determination of low levels of (99)Tc in environmental samples. PMID- 17350275 TI - Synaptic responses in superficial layers of medial entorhinal cortex from rats with kainate-induced epilepsy. AB - Mesial temporal lobe epilepsy patients often display shrinkage of the entorhinal cortex, which has been attributed to neuronal loss in medial entorhinal cortex layer III (MEC-III). MEC-III neuronal loss is reproduced in chronic epileptic rats after kainate-induced (KA) status epilepticus. Here we examined, in vitro, functional changes in superficial entorhinal cortex layers. Alterations in superficial layer circuitry were suggested by showing that presubiculum, parasubiculum and deep MEC stimulation evoked 100-300 Hz field potential transients and prolonged EPSPs (superimposed on IPSPs) in superficial MEC which were partially blocked by APV (in contrast to control) and fully blocked by CNQX. Contrary to controls, bicuculline (5 and 30 microM) had minor effects on evoked field potentials in KA rats. GAD65/67 in situ hybridization revealed preserved interneurons in MEC-III. In conclusion, hyperexcitability in superficial MEC neurons is not due to loss of GABAergic interneurons and probably results from alterations in synaptic connectivity within superficial MEC. PMID- 17350277 TI - Altered D(1) dopamine receptor trafficking in parkinsonian and dyskinetic non human primates. AB - Dyskinesias represent a debilitating complication of levodopa therapy for Parkinson's disease (PD). While we recently demonstrated that levodopa-induced dyskinesia results from increased dopamine D(1) receptor-mediated transmission, we also questioned the possible role of subcellular localization of D(1) and D(2) receptors in mediating these effects as we previously showed that D(1) receptors undergo differential trafficking in striatal neurons of non-dyskinetic PD patients. Taking advantage of a monkey brain bank, we here report changes affecting the cellular and subcellular distribution of D(1) and D(2) dopamine receptors within the striatum of three experimental groups: normal, parkinsonian and dyskinetic L-dopa-treated parkinsonian animals. Our studies at both light and electron microscopy levels show a recruitment of D(1) receptor at the plasma membrane of striatal neurons in the parkinsonian animals and a strong increase of D(1) expression both at the membrane and in cytoplasm of dyskinetic animals, whereas D(2) receptor distribution is only modestly affected in all conditions. Our results rule out the hypothesis of a pathological overinternalization of dopamine receptors in levodopa-induced dyskinesia but raise the possibility for involvement of D(1) receptors in the priming phenomenon through massive and sudden internalization in response to the first ever administration of L-dopa and for an altered homologous desensitization mechanism in dyskinesia leading to an increased availability of D(1) receptors at membrane. Further experiments including parkinsonian monkeys chronically treated with L-dopa that show no dyskinesia and parkinsonian monkeys treated only once with L-dopa are now necessary to confirm our hypothesis. PMID- 17350278 TI - Biological activity of 5-aminolevulinic acid and its methyl ester after storage under different conditions. AB - 5-Aminolevulinic acid (ALA) is a natural precursor of protoporphyrin IX (PpIX) and heme in cells. Photodynamic therapy (PDT) utilizes a metabolic imbalance in cancer cells, leading to increased PpIX generation from exogenous ALA. Due to chemical instability of ALA in therapeutic concentrations at pH values larger than 5.0 and at high temperatures, it looses its activity by spontaneous dimerization to 2,5-dicarboxyethyl-3,6-dihydropyrazine (DHPY). ALA esters are now supplementing ALA in PDT, but little is known about their stability. We have studied the stability of ALA and its methyl ester (MAL) stored under different conditions (temperatures, pH values) by measuring their ability to generate PpIX. 100mM solutions of both compounds were found to be stable at pH 4 and at 4 degrees C. However, at pH 5.5 they lost almost 10% of the initial activity during 5days of storage at 4 degrees C. The fastest decay of ALA and MAL was seen at pH 7.4 and at 37 degrees C, and followed first order kinetics. At pH 7.4 and at 4 degrees C MAL lost its PpIX producing ability more slowly than at 37 degrees C. Our work shows that solutions should be prepared immediately before use and stored at low temperatures. The pH of stock solutions should not exceed 5. PMID- 17350276 TI - Identification of photoreceptor genes affected by PRPF31 mutations associated with autosomal dominant retinitis pigmentosa. AB - Several ubiquitously expressed genes encoding pre-mRNA splicing factors have been associated with autosomal dominant retinitis pigmentosa (adRP), including PRPF31, PRPF3 and PRPF8. Molecular mechanisms by which defects in pre-mRNA splicing factors cause photoreceptor degeneration are not clear. To investigate the role of pre-mRNA splicing in photoreceptor gene expression and function, we have begun to search for photoreceptor genes whose pre-mRNA splicing is affected by mutations in PRPF31. Using an immunoprecipitation-coupled-microarray method, we identified a number of transcripts associated with PRPF31-containing complexes, including peripherin/RDS, FSCN2 and other photoreceptor-expressed genes. We constructed minigenes to study the effects of PRPF31 mutations on the pre-mRNA splicing of these photoreceptor specific genes. Our experiments demonstrated that mutant PRPF31 significantly inhibited pre-mRNA splicing of RDS and FSCN2. These observations suggest a functional link between ubiquitously expressed and retina specifically expressed adRP genes. Our results indicate that PRPF31 mutations lead to defective pre-mRNA splicing of photoreceptor-specific genes and that the ubiquitously expressed adRP gene, PRPF31, is critical for pre-mRNA splicing of a subset of photoreceptor genes. Our results provide an explanation for the photoreceptor-specific phenotype of PRPF31 mutations. PMID- 17350279 TI - Modulation of eotaxin-3 (CCL26) in alveolar type II epithelial cells. AB - Airway epithelial inflammation associated with emphysema, chronic bronchitis, chronic obstructive pulmonary disease (COPD) and asthma is regulated in part by alveolar type II cell chemokine signaling. Data suggest that resident lung cells use CCR3, CCR5 and CCR2 chemokine receptor/ligand systems to regulate the profile of leukocytes recruited in disease-associated inflammatory conditions. Thus studies were designed to test whether alveolar type II cells possess a Th1 activated CCR5-ligand system that modulates the Th2-activated CCR3/eotaxin-2 (CCL24), eotaxin-3 (CCL26) chemokine systems. The A549 alveolar type II epithelial-like cell culture model was used to demonstrate that alveolar type II cells constitutively express CCR5 which may be upregulated by MIP-1alpha (CCL3) whose expression was induced by the Th1 cytokines IL-1beta and IFN-gamma. Selective down-regulation of CCL26, but not CCL24, was observed in CCL3 and IL 4/CCL3 stimulated cells. Down-regulation was reversed by anti-CCR5 neutralizing antibody treatment. Thus, one mechanism through which Th1-activated CCCR5/ligand pathways modulate Th2-activated CCR3/ligand pathways is the differential down regulation of CCL26 expression. Results suggest that the CCR3 and CCR5 receptor/ligand signaling pathways may be important targets for development of novel mechanism-based adjunctive therapies designed to abrogate the chronic inflammation associated with airway diseases. PMID- 17350280 TI - Liquid chromatography electron capture dissociation tandem mass spectrometry (LC ECD-MS/MS) versus liquid chromatography collision-induced dissociation tandem mass spectrometry (LC-CID-MS/MS) for the identification of proteins. AB - Electron capture dissociation (ECD) offers many advantages over the more traditional fragmentation techniques for the analysis of peptides and proteins, although the question remains: How suitable is ECD for incorporation within proteomic strategies for the identification of proteins? Here, we compare LC-ECD MS/MS and LC-CID-MS/MS as techniques for the identification of proteins. Experiments were performed on a hybrid linear ion trap-Fourier transform ion cyclotron resonance mass spectrometer. Replicate analyses of a six-protein (bovine serum albumin, apo-transferrin, lysozyme, cytochrome c, alcohol dehydrogenase, and beta-galactosidase) tryptic digest were performed and the results analyzed on the basis of overall protein sequence coverage and sequence tag lengths within individual peptides. The results show that although protein coverage was lower for LC-ECD-MS/MS than for LC-CID-MS/MS, LC-ECD-MS/MS resulted in longer peptide sequence tags, providing greater confidence in protein assignment. PMID- 17350281 TI - Up-regulation of Connexin43 in the glial scar following photothrombotic ischemic injury. AB - Several types of CNS injury and various diseases are associated with the development of a glial scar. Astrocytes are major components of the glial scar. They are interconnected by gap junctions, with connexin43 (Cx43) being the most prominent channel protein. We applied a model of focal cerebral ischemia to study the spatio-temporal expression of glial fibrillary acidic protein, as well as of Cx43 mRNA and protein in gliotic tissue up to 60 days after injury. Reactive astrocytes enveloping the lesion up-regulated their Cx43 mRNA and protein. A band of reactive astrocytes filling in the lesion exhibited elevated Cx43 and showed a high degree of proliferation. Because of these findings, we hypothesize a role for Cx43 in glial scar formation, specifically in the proliferation of astrocytes. PMID- 17350282 TI - Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory. AB - Learning and memory depend upon poorly defined synaptic and intracellular modifications that occur in activated neurons. Mitogen activated protein kinase extracellular regulated kinase (MAPK-ERK) signaling and de novo protein synthesis are essential aspects of enduring memory formation, but the precise effector molecules of MAPK-ERK signaling in neurons are not well defined. Early growth response (Egr) transcriptional regulators are examples of MAPK-ERK regulated genes and Egr1 (zif268) has been widely recognized as essential for some aspects of learning and memory. Here we show that Egr3, a transcriptional regulator closely related to Egr1, is essential for normal hippocampal long-term potentiation (LTP) and for hippocampal and amygdala dependent learning and memory. In the absence of Egr3, the defects in learning and memory appear to be independent of Egr1 since Egr1 protein levels are not altered in amygdala, hippocampus or cortex. Moreover, unlike Egr1-deficient mice which have impairments in late phase hippocampal LTP and consolidation of some forms of long term hippocampus- and amygdala-dependent memory, Egr3-deficient mice have profound defects in early- and late-phase hippocampal LTP, as well as short-term and long-term hippocampus- and amygdala-dependent learning and memory. Thus, Egr3 has an essential role in learning and memory processing that appears to be partly distinct from the role of Egr1. PMID- 17350283 TI - Differential impact of Lhx2 deficiency on expression of class I and class II odorant receptor genes in mouse. AB - Odorant receptor (OR) genes can be classified into two types: fish-like class I OR genes and mammalian-specific class II OR genes. We have previously shown that Lhx2, a LIM-homeodomain protein, binds to the homeodomain site in the promoter region of mouse M71, a class II OR, and that a knockout mutation in Lhx2 precludes expression of all tested class II OR genes including M71. Here, we report that most class I OR genes, which are expressed in a dorsal region of the olfactory epithelium, are still expressed in Lhx2-deficient embryos. There are two exceptions: two class I OR genes, which are normally expressed in a more ventral region, are no longer expressed in Lhx2 mutant mice. Lhx2 is transcribed in olfactory sensory neurons irrespective of expression of class I or class II OR genes. Thus, a deficiency of Lhx2 has a differential impact on class I and class II OR gene expression. PMID- 17350284 TI - Generation of ribosome nascent chain complexes for structural and functional studies. AB - Biochemical and structural studies of co-translational folding, targeting and translocation depend on an efficient methodology to prepare ribosome nascent chain complexes (RNCs). Here we present our approach for the generation of homogenous and stable RNCs involving in vitro translation and affinity purification. Fusing the SecM arrest sequence, which tightly interacts with the ribosomal tunnel, to the nascent polypeptide chain significantly enhanced the stability of the RNCs. We have been able to increase the yield of the affinity purification step by engineering a tag with higher affinity. The RNCs generated with this approach have been successfully used to obtain 3D cryo-electron microscopic reconstructions of complexes with the signal recognition particle and the translocon. The established procedure is highly efficient and if scaled up could yield milligram amounts of RNCs sufficient for crystallization experiments. PMID- 17350285 TI - Cell-free production of G protein-coupled receptors for functional and structural studies. AB - G-protein coupled receptors (GPCRs) are key elements in signal transduction pathways of eukaryotic cells and they play central roles in many human diseases. So far, most structural and functional approaches have been limited by the immense difficulties in the production of sufficient amounts of protein samples in conventional expression systems based on living cells. We report the high level production of six different GPCRs in an individual cell-free expression system based on Escherichia coli extracts. The open nature of cell-free systems allows the addition of detergents in order to provide an artificial hydrophobic environment for the reaction. This strategy defines a completely new technique for the production of membrane proteins that can directly associate with detergent micelles upon translation. We demonstrate the efficient overproduction of the human melatonin 1B receptor, the human endothelin B receptor, the human and porcine vasopressin type 2 receptors, the human neuropeptide Y4 receptor and the rat corticotropin releasing factor receptor by cell-free expression. In all cases, the long chain polyoxyethylene detergent Brij78 was found to be highly effective for solubilization and milligram amounts of soluble protein could be generated in less than 24 h. Single particle analysis indicated a homogenous distribution of predominantly protein dimers of the cell-free expressed GPCR samples, with dimensions similar to the related rhodopsin. Ligand interaction studies with the endothelin B receptor and a derivative of its peptide ligand ET 1 gave further evidence of a functional folding of the cell-free produced protein. PMID- 17350286 TI - Characterization of a Rab GTPase up-regulated in the shrimp Peneaus japonicus by virus infection. AB - The molecular mechanisms of the immune system against virus in shrimp are not well known, despite its economic importance as an aquaculture species. In this investigation, a Rab gene (named as PjRab gene) was obtained from Peneaus japonicus shrimp, which exhibited high homology with Rab 6 of other species. The PjRab protein, having GTP-binding activity, contained characteristic signatures of Rab proteins with 6 GTP binding domains and 5 Rab specific domains. However, the PjRab protein exhibited a very different prenylation site (CLLNL) at its C terminus from most of other Rabs. The PjRab gene was ubiquitously expressed in shrimp tissues. Real-time PCR revealed that the PjRab gene was up-regulated in WSSV-resistant shrimp, suggesting that the PjRab protein might play an important role in shrimp immune response against virus infection. This discovery might contribute better understanding to the molecular events involved in shrimp as well as invertebrate immune responses. PMID- 17350287 TI - Modulation of carp (Cyprinus carpio) neutrophil functions during an infection with the haemoparasite Trypanoplasma borreli. AB - Trypanoplasma borreli is an extracellular blood parasite of common carp (Cyprinus carpio) transmitted by fish-biting leeches. The infestation with this parasite in juvenile carp may range between 75% and 100%, especially in fish recovering from the first hibernation period. T. borreli is perfectly adapted to its prolonged survival in a cyprinid host. Elevated numbers of activated neutrophils in peripheral blood and tissues are reported during T. borreli infection, but in context of the disease, the direct reason for elevated neutrophil numbers and their role during the infection remain unclear. In this study, a quantitative transmigration system, permitting the harvest of highly pure (> or = 97%) neutrophil populations was applied to investigate the modulation of carp neutrophil functions during T. borreli infection. We demonstrate time-dependent kinetics of a serum-induced down-regulation of neutrophil chemotaxis and an up regulation of ROS production during the course of infection. With highly pure neutrophil populations, we could show that this divergent alteration of neutrophil functions was neither caused by T. borreli metabolites nor by the parasite itself. Moreover, when added to highly purified neutrophils, parasite metabolites did not alter the leukotriene B4-induced neutrophil chemotaxis nor the Staphylococcus aureus-induced ROS production. We conclude that the haemoparasite T. borreli does not interact with neutrophils directly, but indirectly modulates their functions via serum factors induced by parasite interaction with other components of the immune system. PMID- 17350288 TI - Effect of selective fatiguing of the shank muscles on single-leg-standing sway. AB - Control of standing requires the continuous activity of the leg muscles. In single leg standing the system is less redundant and muscular activity is more intensive. The objective of this study was to examine the effect of force imbalance of the shank muscles, evoked by their selective fatiguing, on postural control in single-leg standing. Five healthy subjects performed two single-leg standing trials, lasting as long as the subject could maintain steady balance, and separated by a 240s quasi-isotonic sustained effort to induce fatigue of the Tibialis Anterior and Peroneus muscles. The following were on-line monitored: sway-related parameters, e.g., ground reaction force and center of pressure in the standing trials; and electromyogram of the Tibialis Anterior, Peroneus and Gastrocnemius muscles in all experiments. Simple and multiple linear regressions served to study the fatigue effects on the relationship between muscle activity and postural sway. The results indicate that the evoked muscle imbalance leads to (a) increased postural sway; (b) increased correlation between muscle activity, and sway-related parameters. Thus, with the reduction of the level of redundancy the system becomes more synchronized. These results have potential relevance for cases of muscle impairment, in which electrical stimulation is required to augment muscle activity. PMID- 17350289 TI - Cerebellar contributions to episodic memory encoding as revealed by fMRI. AB - Event-related functional Magnetic Resonance Imaging (fMRI) allows for the comparison of hemodynamic responses evoked by items that are remembered in a subsequent memory task vs. items that are forgotten. In this way, brain regions that assumingly contribute to successful memory encoding have been identified, including the left inferior prefrontal cortex (LIPC) and the medial temporal lobe. Although a cerebellar involvement in verbal working memory is well established, a contribution of the cerebellum to episodic long-term encoding has only sporadically been described, and mechanisms underlying cerebellar memory effects are unclear. We conducted a typical incidental verbal memory fMRI experiment with three different encoding tasks varying the depth of semantic processing. Slice positioning allowed for the coverage of the entire cerebellum. We observed a significant subsequent memory effect within the superior and posterior right cerebellar hemisphere that was task independent. Additionally, we found a different area within the superior right cerebellum displaying a memory effect specifically for semantically processed words and a bilateral cerebellar activation specifically associated with encoding success only for a non-semantic task. Our results suggest that besides its known role in verbal working memory, the cerebellum contributes to episodic long-term encoding and should therefore be considered in future fMRI studies dealing with episodic memory. PMID- 17350290 TI - A tensor based morphometry study of longitudinal gray matter contraction in FTD. AB - Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by progressive behavioural abnormalities and frontotemporal atrophy. Here we used tensor based morphometry (TBM) to identify regions of longitudinal progression of gray matter atrophy in FTD compared to controls. T1-weighted MRI images were acquired at presentation and 1-year follow-up from 12 patients with mild to moderate FTD and 12 healthy controls. Using TBM as implemented in SPM2, a voxel wise estimation of regional tissue volume change was derived from the deformation field required to warp a subject's late to early anatomical images. A whole brain analysis was performed, in which a level of significance of p<0.05 corrected for multiple comparisons (family wise error-FWE) was accepted. Based on prior studies, a region of interest (ROI) analysis was also performed, including in the search area bilateral medial and orbital frontal regions, anterior cingulate gyrus, insula, amygdala and hippocampus. Within this ROI a level of significance of p<0.001 uncorrected was accepted. In the whole brain analysis, the anterior cingulate/paracingulate gyri were the only regions that showed significant atrophy change over 1 year. In the ROI analysis, the left ventro-medial frontal cortex, right medial superior frontal gyrus, anterior insulae and left amygdala/hippocampus showed significant longitudinal changes. In conclusion, limbic and paralimbic regions showed detectable gray matter contraction over 1 year in FTD, confirming the susceptibility of these regions to the disease and the consistency with their putative role in causing typical presenting behaviours. These results suggest that TBM might be useful in tracking progression of regional atrophy in FTD. PMID- 17350291 TI - When goals are missed: dealing with self-generated and externally induced failure. AB - The posterior medial frontal cortex (pMFC) has been consistently implicated in performance monitoring. It is assumed to signal the need for adjustments whenever the outcome of an action is worse than intended. Up to now, monitoring of self generated errors has been in the focus of research. In everyday life, however, also external reasons such as machine malfunction may cause that an action goal is missed, such that compensatory actions are needed. Using functional magnetic resonance imaging (fMRI) we tested whether the pMFC is engaged not only by self generated errors but also by failure to achieve the goal resulting from external reasons and whether performance monitoring activity differs between the two conditions. In a modified flanker task yielding sufficient numbers of self generated errors technical malfunctions were simulated on a subset of correct trials. Malfunctions and errors led to equal fMRI signal increases in the pMFC. The activity time course differed, however; in malfunctions the maximum occurred later than in errors. Moreover, pMFC activity was stronger with increasing time needed for actions compensating the failure to achieve the action goal in the first place. The results suggest that its activity increases when selection of the compensatory action turns out to be more ambiguous and demanding. Thus, no matter of whether adjustments are needed as a result of a self-generated error or external factors, the pMFC plays a prominent role in initiating compensatory actions and in the selection of the appropriate compensation. PMID- 17350292 TI - Molecular evidence and phylogenetic affiliations of Wolbachia in cockroaches. PMID- 17350293 TI - The effects of plasma proteins on delayed repolarization in vitro with cisapride, risperidone, and D, L-sotalol. AB - INTRODUCTION: Drug-induced long QT syndrome (LQTS) has been linked to arrhythmias (including Torsades de Pointes and sudden cardiac death), and has led to an increased awareness of the potential risk of delayed repolarization in vitro and in vivo. However, in vitro assessments of delayed repolarization have not been fully predictive of in vivo effects. METHODS: To define the extent to which plasma protein binding (ppb) contributes to such disparities in repolarization studies, we compared drug-induced prolongation of the canine Purkinje fiber action potential duration (APD(90)) in vitro during superfusion with 100% Tyrode's solution (Tyrodes), canine plasma [50% plasma/50% Tyrodes] and a 5% solution of recombinant human serum albumin in Tyrodes (HSA). Drugs evaluated included cisapride (>98% ppb), risperidone (90% ppb), and d, l-sotalol (negligible ppb). Effects on APD were monitored using standard microelectrode techniques under physiologic conditions and temperature ([K(+)]=4 mM, 37 degrees C) during slow stimulation (2 s basic cycle length). RESULTS: The effects of cisapride and risperidone on Purkinje fiber APD(90) were significantly attenuated in the presence of plasma proteins. However, with cisapride, the extent of reduction with plasma proteins was significantly less than predicted based on calculated free drug levels. DISCUSSION: We conclude that while plasma protein binding does reduce APD prolongation seen with bound drugs, this effect is not well correlated with the calculated plasma protein binding or expected clinical free fraction. Because of the complex drug interactions that occur in plasma, the electrophysiological effects seen with bound drugs are not well correlated with the calculated free fraction and thus caution should be exercised when assigning a predictive safety window. Thus, the canine Purkinje fiber assay is useful for defining the modulation of delayed repolarization due to plasma protein binding of novel therapeutic agents. PMID- 17350294 TI - Neuropathological and MRI findings in an acute presentation of hemiconvulsion hemiplegia: a report with pathophysiological implications. AB - The mechanisms underlying the hemiconvulsion-hemiplegia-epilepsy syndrome (HHE) remain unclear. The current proposed pathogenic mechanism is a neuronal injury induced by venous thrombosis and/or hypoxia. Previous abnormalities of the brain were suggested as underlying mechanism. MATERIALS AND METHODS: We report a patient who presented acutely with hemiconvulsion-hemiplegia (HH) syndrome, but unfortunately died. We discuss the possible pathophysiology of the HH syndrome and possible therapeutic implications utilizing the data from neuroimaging and pathological studies. Post-mortem examination was performed including immunohistochemistry and electron microscopy of the brain tissue. RESULTS: The abnormalities in diffusion-weighted imaging indicate cytotoxic edema of the epileptic hemisphere. The pathological studies confirmed a right homogenous hemispheric edema without evidence of any malformation, inflammatory, infectious or metabolic disease. We found axonal damages in the right thalamus confirmed by anti-neurofilament staining. DISCUSSION: The pathological studies suggest that cytotoxic edema is responsible for neuronal damage. In HH syndrome, two mechanisms playing a role in the development of a later epilepsy could suggest delayed cell death induced by cytotoxic edema and/or thalamic dysfunction causing a disruption of thalamo-cortical circuit. In acute presentation, the use of anti edema therapy should be discussed to prevent the cell injury. PMID- 17350295 TI - Differential expression of leptin and leptin's receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. AB - OBJECTIVE: To investigate leptin's effect on cartilage metabolism and the pathophysiology of osteoarthritis (OA). METHODS: Messenger RNA (mRNA) expression and protein levels of leptin and leptin's receptor isoforms were measured by real time reverse transcription-PCR and Western blot in osteoarthritic and normal cartilage. Osteoarthritic cartilage samples were obtained from two locations of the knee (n=11) and hip (n=6); from the main defective area (advanced OA) and from adjacent macroscopically and histological intact regions (minimal OA). Paired serum and synovial fluid (SF) leptin levels were measured. The effect of leptin was evaluated on chondrocyte proliferation, IL-1beta (interleukin-1beta), NO and metalloproteinases 9 and 13 (MMP-9, MMP-13) protein expression. RESULTS: Leptin's and leptin's receptor (Ob-Rb) expression levels were significantly increased in advanced OA cartilage compared to minimal. Leptin was significantly increased in SF than serum samples. Also, leptin had a detrimental effect on chondrocyte proliferation and induced IL-1beta production and MMP-9 and MMP-13 protein expression. Furthermore, leptin's mRNA expression in advanced OA cartilage was significantly correlated with BMI of the patients. CONCLUSION: The increased leptin levels in SF point toward a local effect of leptin in articular cartilage, while the observed intrajoint differences of leptin and Ob-Rb mRNA expression may be related to the grade of cartilage destruction. The observed production of IL-1beta, MMP-9 and MMP-13 by chondrocytes after leptin treatment indicates a pro-inflammatory and catabolic role of leptin on cartilage metabolism. Furthermore, the observed correlation of leptin's mRNA expression with BMI suggests that leptin may be a metabolic link between obesity and OA. PMID- 17350297 TI - The expression of CXCR4 is down-regulated on the CD34+ cells of patients with myelofibrosis with myeloid metaplasia. AB - PURPOSE: We studied the expression of the chemokine receptor CXCR4 on circulating CD34+ cells of patients with myelofibrosis with myeloid metaplasia (MMM), and examined its relationship to the severity of disease. PATIENTS AND METHODS: Surface and intracellular CXCR4 expression were measured flow cytometrically in 84 consecutive MMM patients, 16 patients with polycythemia vera (PV), and 20 healthy subjects. In 23 MMM patients, CXCR4 gene expression level was also quantitated by real time-RT-PCR in CD34+ cells. RESULTS: The expression of CXCR4 on circulating CD34+ cells was significantly reduced in patients with MMM (P<0.001) as compared to normal controls and patients with PV (P=0.01). The levels of CXCR4 mRNA in CD34+ cells were lower in patients with MMM as compared with normal subjects, and were directly correlated with the degree of CXCR4 surface expression, demonstrating that transcriptional defects were the major cause for receptor down-regulation. No statistical association was found between JAK2V617F mutational status and the extent of CXCR4 down-regulation. CXCR4 expression on CD34+ cells inversely correlated with the number of circulating CD34+ cells (R=-0.55; P<0.001), and was severely down-regulated in high risk patients and patients with a high "myelodepletion severity index". CXCR4 down regulation was associated with advanced patient age, the presence of severe anemia, thrombocytopenia, and degree of bone marrow fibrosis. CONCLUSIONS: Reduced expression of CXCR4 by CD34+ cells is a characteristic of MMM which is associated with the constitutive mobilization of CD34+ cells and occurs in patients with advanced forms of the disease. PMID- 17350296 TI - Behavioral characterization of a transection of dorsal CA3 subcortical efferents: comparison with scopolamine and physostigmine infusions into dorsal CA3. AB - Cholinergic projections from the medial septum and diagonal band of Broca into the hippocampus have long been implicated in learning and memory. Projections from CA3 to neurons in the medial septum and the diagonal band of Broca have been anatomically characterized. The present experiments were designed to evaluate interactions between the dorsal CA3 subcortical efferents and the cholinergic efferents from the medial septum and diagonal band of Broca for spatial and nonspatial (visual object) novelty detection in the rat. In Experiment 1, physostigmine and scopolamine (both 0.4 microL at 30 microM) were infused into dorsal CA3 and animals were tested on a spatial and nonspatial (visual object) novelty detection paradigm. Scopolamine infusions into dorsal CA3 caused deficits for both spatial and nonspatial (visual object) novelty detection. Physostigmine infusions into dorsal CA3 enhanced both spatial and nonspatial (visual object) novelty detection. These data support models proposing that acetylcholine may control the dynamics for encoding, consolidation, and retrieval in the hippocampus. In Experiment 2, a selective transection of dorsal CA3 efferents in the fimbria resulted in deficits for spatial and nonspatial (visual object) novelty detection. These deficits were similar to the deficits caused by scopolamine infusions into dorsal CA3. These data demonstrate that dorsal CA3 and the medial septum/diagonal band of Broca interact, and that dorsal CA3 influences cholinergic inputs into the hippocampus to facilitate encoding. PMID- 17350298 TI - Insights into ligand selectivity in nitric oxide synthase isoforms: a molecular dynamics study. AB - Molecular dynamics (MD) simulations were carried out for inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms complexed with substrate (L-arginine) and the iNOS specific inhibitor GW 273629, 2 for a time period of 1.2ns. The simulations were compared both within and across the isoforms. iNOS specificity of inhibitor 2 is attributed to water mediated interactions and cooperative hydrogen bond networks. Juxtaposition of the carboxylic and ammonium groups in the substrate and inhibitor serve as a modulating key in binding to the isoforms. Based on these investigations, molecules 3 and 4 were rationally designed to attain specificity among the isoforms. The capability of the designed ligands was theoretically tested through MD simulations to envisage binding patterns with both isoforms. A detailed analysis of the molecular recognition pattern shows molecule 4 to be more selective to iNOS when compared to eNOS. PMID- 17350299 TI - Branchial carbonic anhydrase activity and ninhydrin positive substances in the Pacific white shrimp, Litopenaeus vannamei, acclimated to low and high salinities. AB - The Pacific white shrimp, Litopenaeus vannamei, acclimated to 30 ppt salinity, was transferred to either low (15 and 5 ppt), or high (45 ppt) salinity for 7 days. Hemolymph osmolality, branchial carbonic anhydrase activity, and total ninhydrin-positive substances (TNPS) in abdominal muscle were then measured for each condition. Hemolymph osmotic concentration was regulated slightly below ambient water osmolality in shrimp acclimated to 30 ppt. At 15 and 5 ppt, shrimp were strong hyper-osmotic regulators, maintaining hemolymph osmolality between 200 and 400 mOsm above ambient. Shrimp acclimated to 30 ppt and transferred to 45 ppt salinity were strong hypo-osmotic and hypo-ionic regulators, maintaining hemolymph osmolality over 400 mOsm below ambient. Branchial carbonic anhydrase (CA) activity was low (approximately 100 micromol CO(2) mg protein(-1) min(-1)) and uniform across all 8 gills in shrimp acclimated to 30 ppt, but CA activity increased in all gills after exposure to both low and high salinities. Anterior gills had the largest increases in CA activity, and levels of increase were approximately the same for low and high salinity exposure. Branchial CA induction appears to be functionally important in both hyper- and hypo-osmotic regulations of hemolymph osmotic concentrations. Abdominal muscle TNPS made up between 19 and 38% of the total intracellular osmotic concentration in shrimp acclimated to 5, 15, and 30 ppt. TNPS levels did not change across this salinity range, over which hemolymph osmotic concentrations were tightly regulated. At 45 ppt, hemolymph osmolality increased, and muscle TNPS also increased, presumably to counteract intracellular water loss and restore cell volume. L. vannamei appears to employ mechanisms of both extracellular osmoregulation and intracellular volume regulation as the basis of its euryhalinity. PMID- 17350300 TI - Gametogenesis correlated with steroid levels during the gonadal cycle of the sea urchin Paracentrotus lividus (Echinodermata: Echinoidea). AB - The specific mechanism regulating reproduction in invertebrates is a field of topical interest which needs to be explored in detail considering also the intriguing possible comparison with vertebrates. In this paper levels of Testosterone (T) and Estradiol (E2) and their reciprocal ratios were determined in ovaries and testis of the echinoid model species Paracentrotus lividus during the year 2004 by taking into account a putative relationship between steroid levels and reproductive cycle. T levels appeared to significantly vary during male reproductive cycle, thus suggesting a possible role of this hormone in regulation of spermatogenesis as demonstrated for other echinoderms. E2 levels were lower in males with respect to females; consequently E2 involvement in oogenesis is hypothesized. In parallel with steroid levels evaluation, variations in P450-aromatase activity and its possible role on regulation of gametogenesis were also considered. Clear correlations between steroid levels and gonad index (GI), as well as between GI and reproductive cycle were not detected, suggesting that GI alone is not a reliable parameter in describing the reproductive status of the gonads. Altogether the results obtained so far confirm the presence of a relationship between steroid levels and reproductive cycle as suggested by previous results on different echinoderm species. PMID- 17350301 TI - Purification and biochemical characterization of a 70 kDa sericin from tropical tasar silkworm, Antheraea mylitta. AB - Sericin isolated from the cocoon of the tropical tasar silkmoth Antheraea mylitta showed three major bands, with the lowest 70 kDa. This band was purified by anion exchange chromatography. Immunoblotting with concanavalin-A suggests a glycoprotein and CD analysis of secondary structure includes beta-sheet. Amino acid analysis shows that the protein is enriched in glycine and serine while the mole percentages of these two amino acids are different from sericin of mulberry silkworm. An anti A. mylitta sericin antibody was able to cross-react with sericin from A. assamensis but not the sericin of Bombyx mori and Philosamia ricini. Immunoblot analysis with proteins isolated from middle silk gland of A. mylitta at different developmental stages of larva showed that the 70 kDa sericin is developmentally regulated. These data extend the range of biochemical features found in this unusual family of proteins and may help in developing an improved understanding of their role in forming environmentally stable fibroin fiber sericin composite structures (cocoons). PMID- 17350302 TI - Effects of heterozygosity for the E180 splice mutation causing growth hormone receptor deficiency in Ecuador on IGF-I, IGFBP-3, and stature. AB - CONTEXT & OBJECTIVE: The Ecuadorian GH receptor deficiency (GHRD)/Laron syndrome population is the only large cohort with a single GHR mutation (E180 splice), permitting identification of numerous carrier and noncarrier first-degree relatives, to ascertain effects of heterozygosity on GH-dependent IGF-I and IGFBP 3 concentrations and on growth. DESIGN: First-degree relatives (n=212) of GHRD patients had specimens taken for IGF-I, IGFBP-3, and GHR genotyping. Normal statured (n=40) and short statured (n=40) unrelated controls had measurement of IGF-I, IGFBP-3, and stature. RESULTS: There were no significant differences between heterozygous and homozygous normal relatives in IGF-I or IGFBP-3 standard deviation scores (SDS). Heterozygous relatives had lower mean height SDS than did homozygous normals, but with extensive overlap between genotype groups in both child and adult relatives. Height SDS in general did not relate to IGF-I or IGFBP 3 concentrations. CONCLUSIONS: GH-dependent IGF-I and IGFBP-3 secretion is not affected by heterozygosity for the E180 splice mutation that causes GHRD/Laron syndrome in the Ecuadorian population. Heterozygosity is associated with reduction in mean statural SDS, but this is not sufficient to be clinically important and not mediated through measurable differences in circulating IGF-I or IGFBP-3 related to genotype. PMID- 17350303 TI - Immunolocalization of insulin-like growth factor I (IGF-I) during preimplantation in rat uterus. AB - OBJECTIVE: The aim of this study was to determine the insulin-like growth factor (IGF-I) immunolocalization in rat uterus at preimplantation period. DESIGN: The tissue samples were examined from pregnant animals between gestational day 1 and 5 using immunocytochemistry. RESULTS: While both the uterine luminal epithelium and the glandular epithelium were stained strongly from gestational day 1 - 3 by IGF-I antibody, the IGF-I immunoreactivity was moderate in myometrium and capillary endothelium. At this period, the IGF-I immunoreactivity was weakly present in a few endometrial stromal cells. At day 4, while IGF-I immunostaining intensity was particularly decreased in the basal domains of uterine luminal epithelium and glandular epithelium, it was similar to the first 3 days of gestation in myometrium and capillary endothelium. The endometrial vascularization and the number of stromal cells immunoreacting with IGF-I increased. The differentiation of stromal cells into decidual cells was seen at gestational day 5 and IGF-I was strongly expressed in the decidualizing cells. The IGF-I immunoreactivity in uterine luminal epithelium and glandular epithelium was similar to gestational day 4. IGF-I immunoreactivity was strongly detected in all of endometrial stromal cells. CONCLUSION: These results indicate that IGF-I expression in the rat uterus changes in the early pregnancy process and increase toward to day when implantation will be initiated. PMID- 17350304 TI - Maggot excretions/secretions inhibit multiple neutrophil pro-inflammatory responses. AB - There is renewed interest in the use of maggots (Lucilia sericata) to aid in healing of chronic wounds. In such wounds neutrophils precipitate tissue damage rather than contribute to healing. As the molecules responsible for the beneficial actions of maggots are contained in their excretions/secretions (ES), we assessed the effects of ES on functional activities of human neutrophils. ES dose-dependently inhibited elastase release and H(2)O(2) production by fMLP activated neutrophils; maximal inhibition was seen with 5-50 microg of ES/ml. In contrast, ES did not affect phagocytosis and intracellular killing of Candida albicans by neutrophils. Furthermore, 0.5 microg of ES/ml already inhibited neutrophil migration towards fMLP. ES dose-dependently reduced the fMLP stimulated expression of CD11b/CD18 by neutrophils, suggesting that ES modulate neutrophil adhesion to endothelial cells. ES did not affect the fMLP-induced rise in [Ca(2+)](i) in neutrophils, indicating that ES act down-stream of phospholipase C-mediated activation of protein kinase C. In agreement, ES inhibited PMA-activated neutrophil functional activities. ES induced a rise in intracellular cAMP concentration in neutrophils and pharmacological activators of cAMP-dependent mechanisms mimicked their inhibitory effects on neutrophils. The beneficial effects of maggots on chronic wounds may be explained in part by inhibition of multiple pro-inflammatory responses of activated neutrophils by ES. PMID- 17350305 TI - Evaluation of antimicrobial regimens in a guinea-pig model of meningitis caused by Pseudomonas aeruginosa. AB - To compare the efficacy of meropenem, ceftazidime, tobramycin and ceftazidime+tobramycin in a guinea-pig model of P. aeruginosa meningitis. After anesthesia, the atlanto-occipital membrane was punctured with a butterfly needle and 100 microl of a solution containing 10(6)CFU/ml of P. aeruginosa were injected directly into the cisterna magna. Four h later, therapy was initiated with saline or antibiotics given im for 48 h in doses that obtained CSF levels as in human meningitis: ceftazidime 200 mg/kg/8h, meropenem 200 mg/kg/8h, tobramycin 30 mg/kg/24h. Tobramycin was also given intracisternally. Animals were sacrificed at different time points. CSF and blood samples were collected and a meningeal swab was performed. Four hours after inoculation, bacterial concentration in CSF was 4 to 5log10CFU and mean WBC was 16,000/-l. All control animals died in 24h with a 12% increase in cerebral edema. All blood-cultures were negative. Ceftazidime, ceftazidime+tobramycin and meropenem reduced the CSF bacterial concentration at 8h by 2.5log10. At 48 h all CSF cultures were sterile but meningeal swab cultures remained positive in 30%. Our results suggest that meropenem may be at least as effective as ceftazidime and that the addition of tobramycin to ceftazidime may improve its efficacy. PMID- 17350306 TI - Antimonial treatment of visceral leishmaniasis: are current in vitro susceptibility assays adequate for prognosis of in vivo therapy outcome? AB - In most of the Indian subcontinent, the first line treatment for visceral leishmaniasis (VL) is sodium stibogluconate (SSG), an antimonial drug, but the efficacy of the drug varies according to region. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Nepalese VL patients, and to correlate this in vitro parasite phenotype to clinical therapy outcome. Thirty three clinical isolates of L. donovani were taken from patients with known disease history. These isolates were typed and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined. We observed (i) 22 SbV-resistant isolates out of 33 tested and (ii) 3 SbIII-resistant isolates out of 12 tested. Amongst the latter, there were three combinations of in vitro phenotypes: (i) parasites sensitive (n=4) or (ii) resistant to both drugs (n=3) and (iii) resistant to SbV only (n=5). There was no geographical clustering in terms of in vitro susceptibility. The relation between the in vitro susceptibility to antimonials and the corresponding in vivo treatment outcome was ambiguous. Our results highlight the need to adjust the currently used Leishmania drug susceptibility assays if they are to be used for prognosis of in vivo SSG treatment outcome. PMID- 17350307 TI - Generation of specific Th1 and CD8+ T-cell responses by immunization with mouse CD8+ dendritic cells loaded with HIV-1 viral lysate or envelope glycoproteins. AB - Immunization with antigen-pulsed dendritic cells (DCs) can be used to elicit optimal immune responses. We developed the SRDC cell line, with a morphology, phenotype and activity similar to mouse splenic CD4(-)CD8alpha(+)CD205(+)CD11b(-) dendritic cells, which induce a polarized Th1 immune response. We evaluated the ability of SRDCs pulsed with HIV-1 viral lysate, oligomeric soluble gp140 or capsid p24 to induce specific antibody and T-cell responses in CBA/J mice. Immunization with all loaded SRDCs elicited antibody responses against the antigens tested. However, only HIV-1 viral lysate and gp140-pulsed SRDCs elicited specific CD4(+) and CD8(+) T-cell responses. These findings demonstrate the value of well characterized DC lines for optimizing the antigen-loading mixture, according to the DC population targeted. Our data suggest that splenic DCs pulsed with complex antigens, such as HIV-1 viral lysate or oligomeric soluble gp140, could be used as vaccines, eliciting strong primary Th1-polarized and humoral immune responses against HIV proteins in vivo. PMID- 17350308 TI - Construction of a novel SHIV having an HIV-1-derived protease gene and its infection to rhesus macaques: a useful tool for in vivo efficacy tests of protease inhibitors. AB - We generated a novel SHIV (termed SHIV-pr) that possesses the HIV-1-derived protease (PR) gene in the corresponding position in the SIVmac genome. SHIV-pr is replication-competent in human and monkey CD4(+) T lymphoid cell lines as well as rhesus macaque PBMCs. The viral growth of SHIV-pr was completely blocked in the presence of a peptide-analog PR inhibitor at the tissue culture level. When SHIV pr was intravenously inoculated into two rhesus macaques, it resulted in a weak but long-lasting persistent infection in one monkey, whereas the infection of another was only temporary. To enhance the viral growth competence by adaptation, we then passaged the virus in vivo from a monkey up to the fourth generation. The initial peak values of plasma viral loads as well as the setpoint values increased generation by generation and reached those of a parental virus SIVmac. When a medication using the content of Kaletra capsule (a mixture of two PR inhibitors, lopinavir and ritonavir) was orally given to three SHIV-pr-infected monkeys for 4 weeks, plasma viral loads dropped to near or below the detection limit and quickly rebounded after the cessation of medication. The results suggest that SHIV-pr can be used to evaluate PR inhibitors using monkeys. PMID- 17350309 TI - Hallux valgus in a historical French population: paleopathological study of 605 first metatarsal bones. AB - OBJECTIVES: To estimate the prevalence of hallux valgus in a historical population in France, to identify associated skeletal abnormalities, and to look for an influence of footwear changes through time. METHODS: We studied the 605 first metatarsals found in the necropolis of the Notre-Dame-du-Bourg cathedral in Digne in the Alpes-de-Hautes-Provence region of southern France. The necropolis contains remains from the 5th to the 17th century. RESULTS: Hallux valgus was identified only in individuals older than 30years at death, and its prevalence increased significantly with age. Exostosis at the medial and dorsal aspects of the head of the first metatarsal were common in advanced forms. The prevalence was comparable in males and females in the Middle Ages but was significantly higher in males in the 16th and 17th centuries, whereas in contemporary populations females are selectively affected. CONCLUSIONS: The increase in the prevalence of hallux valgus over time suggests an influence of changes in footwear. The heeled shoes and boots made of stiff leather that men wore in premodern times probably promoted the development of hallux valgus. However, the prevalence of hallux valgus in women in western industrialized countries today is even higher than that in our historical population of older premodern individuals, suggesting an extremely deleterious effect of contemporary female footwear. PMID- 17350310 TI - Comment on Pavy et al.'s original article "Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion". PMID- 17350311 TI - Amyloid deposition in knee and ankle joints in the course of multiple myeloma. PMID- 17350313 TI - Periarteritis nodosa and AL amyloidosis: a case report. PMID- 17350312 TI - Ankylosing spondylitis, HLA-B27 positivity and the need for biologic therapies. AB - OBJECTIVES: HLA-B27 positivity strongly influences Ankylosing spondylitis (AS) disease susceptibility and phenotype. The aim of this study was to analyse an AS cohort with respect to quality of life (ASQoL), extra-articular disease, markers of disease activity (BASDAI), functional capacity (BASFI), biologic requirement, and the influence of HLA-B27 on these parameters. METHODS: Data recorded in 82 patients included demographics (age, sex), extra-articular disease (GI, ocular, dermatological, GU), cardiac and pulmonary diagnoses. BASDAI, BASFI, ASQoL, joint counts, disease duration and past/present treatment (NSAID, DMARD, steroid and biologic use) were also recorded. RESULTS: 90.2% of the cohort was B27 positive with significantly longer disease duration (17.6 v 6.9 years, p<0.05). BASFI (42.2 v 5.9), BASDAI (3.22 v 1.3), ASQoL (10 v 4), physician assessment of biologic need (24 v 5), steroid (15.7% v 12.5%) and NSAID use (98.6% v 75%) were higher in the B27 positive group, as were ocular (38.9% v 12.5%), pulmonary (4.2% v 0%) and cardiac (4.3% v 0%) features. Negative patients displayed more GI (37.5% v 19.4%), dermatological (25% v 19.7%) and GU (25% v 4.2%) features. Patients satisfying ASAS (AS assessment study group) criteria and receiving biologic therapy were 18.9% (B27 positive group) and 0% (B27 negative group). CONCLUSIONS: AS patients have significantly longer disease duration if B27 positive, higher markers of disease activity, poorer functional status, poorer quality of life, and more extra-articular manifestations. These findings were reflected in the percentage of patients needing biologic therapies. PMID- 17350316 TI - A mild and efficient ultrasound-assisted synthesis of diaryl ethers without any catalyst. AB - Diaryl ethers have been prepared by a mild and efficient S(N)Ar reaction by coupling of various phenols including that having a electron-withdrawing group with activated fluoroarenes using sonication in good to excellent yields at very low temperature (58 degrees C) under catalyst-free. PMID- 17350315 TI - [Screening for Down syndrome using first-trimester combined screening followed by second trimester ultrasound examination in an unselected population]. AB - BACKGROUND: Recent studies have reported the efficacy of first trimester combined screening for Down Syndrome based on maternal age, serum markers (human chorionic gonadotropin, pregnancy-associated plasma protein A), and ultrasound measurement of fetal nuchal translucency. However, those do not incorporate the value of the widely accepted routine 20-22 week anomaly scan. STUDY DESIGN: We carried out a multi-centre, interventional study in the unselected population of a single health authority in order to assess the performance of first trimester combined screening, followed by routine second trimester ultrasound examination and/or screening by maternal serum markers (free beta-hCG and alpha-fetoprotein measurement or total hCG, alpha-fetoprotein and unconjugated estriol measurement) when incidentally performed. Detection and screen positive rates were estimated using a correction method for non verified issues. A cost analysis was also performed. RESULTS: During the study period, 14,934 women were included. Fifty one cases of Down Syndrome were observed, giving a prevalence of 3.4 per 1000 pregnancies. Of these, 46 were diagnosed through first (N=41) or second (N=5) trimester screening. Among the 5 screen-negative Down syndrome cases, all were diagnosed postnatally after an uneventful pregnancy. Detection and screen positive rates of first trimester combined screening were 79.6% and 2.7%, respectively. These features reached 89.7 and 4.2%, respectively when combined with second trimester ultrasound screening. The average cost of the full screening procedure was 108 euro (120 $) per woman and the cost per diagnosed Down syndrome pregnancy was 7,118 euro (7,909 $). CONCLUSION: Our findings suggest that one pragmatic interventional two-step approach using first-trimester combined screening followed by second trimester detailed ultrasound examination is a suitable and acceptable option for Down syndrome screening in pregnancy. PMID- 17350317 TI - Ultrasound induced formation of paraffin emulsion droplets as template for the preparation of porous zirconia. AB - The paraffin particles were prepared by quenching process after sonicating the solution of paraffin and water at 80 degrees C. The resultant paraffin particles were then used as template for the preparation of macroporous zirconia materials. For this, zirconium normal butoxide (ZNB) modified with triethanolamine (TEA) was first hydrolyzed by water containing the dispersed paraffin particles with the surfactant, Sodium di(2-ethylhexyl) sulfosuccinate. This resulted in the formation of a slurry consisting of hydrolyzed sol and paraffin particles. After centrifugation, a cake packed with hydrated sol and paraffin particles were obtained which was then subjected to heat treatment. The sample obtained after heat treatment contained finely dispersed pores in the size range from 40 nm to 2 microm. Moreover, using the present approach it has also been observed that, change in pore size of zirconia wall is possible with a change in size of the paraffin particles. Thus, the present approach is a novel way of producing porous materials as the particle size of the template could be changed and templates become hard when they were molded as compared to the conventional methods in which there is no change in phase for the templates under 100 degrees C. PMID- 17350318 TI - Sonochemical decolorization of acid black 210 in the presence of exfoliated graphite. AB - The decolorization of acid black 210 by ultrasonic irradiation in the presence of exfoliated graphite was investigated. Low pH value and large exfoliation volume of exfoliated graphite favored the ultrasonic decolorization of acid black 210. The combination method of ultrasonic waves and exfoliated graphite achieved better results than either exfoliated graphite or ultrasound alone. Improved decolorization efficiency has been observed in the present system compared to the process using a combination of ultrasound and activated carbon. In the combination method of ultrasonic waves and exfoliated graphite, approximately 99.5% of acid black 210 was removed using 0.8 g/l exfoliated graphite at a pH of 1 within 120 min at 51 degrees C. PMID- 17350320 TI - Treating patients with Gaucher disease and parkinsonism: misrepresentation in a title. PMID- 17350321 TI - c-Kit--a hematopoietic cell essential receptor tyrosine kinase. AB - The receptor tyrosine kinase c-Kit is expressed in hematopoietic stem and progenitor cells and in several non-hematopoietic tissues. In the hematopoietic system, c-Kit is critical for proliferation, survival and differentiation. During recent years exploration of the signalling pathways downstream of this receptor has yielded significant new insights in the field. In this review, we will summarise the c-Kit background, structure, downstream signalling and medical significance with particular focus on its role in hematopoietic progenitor cells and mast cells. PMID- 17350322 TI - Multiple paths to a drug resistance phenotype: mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs. AB - The remarkable responses observed with imatinib (Gleevec) in the therapy of CML led many scientists to think that drug resistance, long recognized as a problem with "cytotoxic" agents, would soon become a thing of the past. But then reality set in. We learned that imatinib, a wonderful drug by any measure, was also susceptible to the development of resistance, as was gefitinib (Iressa), and then erlotinib (Tarceva). This evidence on resistance to "novel agents" together with new data on the complexity of cancer, the rapidly evolving story of microRNAs and their diverse roles, as well as evidence of the importance of epigenetic changes have allowed us to refine our models of drug resistance and how cells acquire these phenotypes. In this overview I will look at examples of how drug resistance develops including older and more recent data on the role of mutations, translocations, deletions, and amplification. The role of epigenetic changes and microRNAs will be discussed, as examples of different mechanisms by which a cell achieves the same end. Recurrent themes that have emerged will be underscored as we seek to understand how drug resistance occurs. PMID- 17350323 TI - Recent advances in the treatment of salivary gland cancers: emphasis on molecular targeted therapy. AB - Salivary gland cancers include tumors of different histologic characteristics and biological behavior. Radical surgery, followed or not by radiation therapy, represents the main treatment approach for this disease. The role of systemic chemotherapy is less clearly defined since trials of single-agent chemotherapy have consistently shown low response rates. Polychemotherapy is likely to induce a higher response rate, but does not improve survival. The determination of the molecular abnormalities underlying the different subtypes of salivary gland cancers might lead to more active targeted therapies. C-kit is overexpressed in a wide percentage of salivary gland carcinomas, but clinical trials with single agent imatinib have been negative. ErbB1 and ErbB2 are also frequently overexpressed in salivary gland cancers and this has provided the rationale for clinical trials with trastuzumab, cetuximab, gefitinib, lapatinib. Finally, new pathways, such as vascular endothelial growth factor, might be worth targeting and clinical trials with anti-angiogenic agents are ongoing. PMID- 17350324 TI - Non-invasive measurement of the morphology and physiology of oral mucosa by use of optical spectroscopy. AB - Differential path-length spectroscopy (DPS) was used to non-invasively determine the superficial optical properties of oral mucosa in vivo. DPS yields information on physiological parameters such as the mucosal blood content, the microvascular blood oxygenation and the average micro-vessel diameter as well as on morphological parameters such as the scattering slope and scattering amplitude. DPS measurements were made on normal and cancerous oral mucosa using a novel fiber-optic probe, and were correlated to the histological outcome of punch biopsies taken from the same location. Our data shows that the mucosa of oral squamous cell carcinoma is characterised by a significant decrease in microvascular oxygenation and increase in mucosal blood content compared to normal oral mucosa as well as a significant decrease in scattering amplitude and increase in scattering slope. PMID- 17350325 TI - Epidemiological and histopathological data and E-cadherin-like prognostic factors in early carcinomas of the tongue and floor of mouth. AB - Despite recent advances in diagnosis and treatment, overall survival of people with squamous cell carcinomas of the tongue and mouth floor continues to be low. Prognostic information is essential for improved evaluation and treatment. A molecular approach is necessary for a better understanding of cancer. We analyzed 50 patients with early squamous cell carcinoma (stages I and II - AJCC, 1997), who were surgically treated in head and neck departments at Heliopolis Hospital and Santa Casa in Sao Paulo, Brazil. We searched for epidemiological and pathological behaviors that could be involved in tumor recurrence and the influence of cellular adhesion loss in patient outcome. We established two groups: patients with disease recurrence within 3 years of follow-up and patients with no cancer recurrence in this period. Significant prognostic variables included age, daily alcohol intake, neural invasion and maximum tumor thickness. Our findings are similar to other published data in which younger patients have a better prognosis. The odds ratio for neural invasion was low but was significant for thickness. No significant difference was observed among groups in E-cadherin expression. Our data suggest that 3 and 5mm are the prognostic determinants of thickness. E-cadherin mutation was not related to recurrences but was associated with locally aggressive invasion patterns. PMID- 17350326 TI - DNA ploidy, proliferative capacity and intratumoral heterogeneity in primary and recurrent head and neck squamous cell carcinomas (HNSCC)--potential implications for clinical management and treatment decisions. AB - Despite new diagnostic and therapeutic strategies (combined radiochemotherapy, EGFR antibody Cetuximab), the prognosis of head and neck squamous cell carcinoma (HNSCC) is still poor and more information regarding prognosis is essential to establish earlier and better treatment options. To elucidate the role of DNA ploidy and cellular proliferation, resected tumors of 48 patients with primary or recurrent HNSCC were analyzed by flow cytometry and in vitro-5-bromodeoxyuridine incorporation (BrdU). The results were compared with histopathological findings such as tumor size, lymph node involvement and tumor differentiation. To assess the influence of intratumoral heterogeneity of these biological parameters, multiple biopsies (>3) were analyzed by flow cytometry and BrdU-incorporation in 12 larger (>4 cm diameter) tumors. BrdU-labeling index (LI%) was significantly higher in aneuploid HNSCC and correlated significantly with poor histologic differentiation of the analyzed tumor tissues (P<0.001). Furthermore, a trend for higher LI% in nodal positive tumors was observed. Aneuploid HNSCC showed significantly more often tissue dedifferentiation (P=0.049) and in most cases an advanced tumor stage, especially in tumors with biclonal cell lines. Lymph node involvement was also seen more often in aneuploid and undifferentiated tumors. As in aneuploid tumors recurrent HNSCC showed in most cases a higher LI% and poor tissue differentiation, but as a result of the small collection of samples there was no correlation between aneuploidy and tumor recurrence. To proof the robustness of the acquired data and to estimate the influence of intratumoral heterogeneity to ploidy and LI% multiple biopsies were analyzed in larger tumors. Using a specific statistical algorithm a secure estimation of ploidy and LI% was possible by a single biopsy in these tumors. These findings indicate aneuploidy and proliferative activity as important findings for malignant progression in HNSCC. An estimation of these biological parameters may be useful for identification of patients with high risk for lymph node involvement or tumor recurrence and pre-treatment can be performed by a single biopsy. As a conclusion, these patients may benefit from more aggressive treatment. PMID- 17350327 TI - Neoadjuvant concurrent radiochemotherapy followed by surgery in advanced oral squamous cell carcinoma (OSCC): a retrospective analysis of 207 patients. AB - Locally advanced operable oral squamous cell carcinoma (OSCC) continues to be a major therapeutic challenge despite the implementation of novel multi-modal treatment approaches. To improve local and local-regional control and to allow functional reconstruction after ablative surgery, neoadjuvant protocols have been developed during the last decade implementing radiochemotherapy prior to selective surgery. In the present retrospective analysis, the results of concurrent radiotherapy with 40 Gy and low-dose cisplatin-based chemotherapy followed by major surgery are presented for n=207 patients with an OSCC of stage III or IV. The overall survival for all patients analyzed was 49.5% after 60 months and 37.0% after 120 months. Further subgroup analysis found that histopathologic N0 tumours had a significantly better 5-year and 10-year overall survival rate than N+ tumours (p=0.004). In multivariate analysis, only postoperative N0 stage was a significant predictor for a favourable outcome (p=0.004). Overall disease-free survival of the whole patient collective was 70.4% after 60 months and 62.6% after 120 months with superior 60 month and 120 month disease-free survival for T0 (p=0.018) and N0 tumours (p=0.007), which was verified by multivariate analysis (p=0.019 and p=0.055, respectively). T+ tumours inherited a 2.5-fold increased risk for the development of local or loco-regional failure (p=0.05), and N+ tumours a 6.1-fold increased risk for the development of distant metastases (p<0.001). In conclusion, neoadjuvant radiochemotherapy with 40 Gy and concurrent low-dose cisplatin monotherapy followed by selective surgery is a feasible and reliable therapy concept, which results in encouraging overall and disease-free survival rates for therapy responders and which reliably selects therapy non-responders by the histopathological assessment of the neck dissection preparation. Those therapy non-responders might profit from intensified systemic therapy approaches. PMID- 17350328 TI - The determination of the levels of circulating galectin-1 and -3 in HNSCC patients could be used to monitor tumor progression and/or responses to therapy. AB - To evaluate galectin-1, -3 and -7 serum levels as diagnostic and/or prognostic markers for head and neck squamous cell carcinomas (HNSCCs). ELISA was employed to test sera from 102 patients with HNSCCs and from 38 healthy control volunteers for galectin-1, -3 and -7 serum levels. Serum galectin levels were assayed by ELISA and the levels of galectin expression in HNSCCs were determined by means of immunohistochemistry. HNSCCs display significant immunohistochemical amounts of galectin-7, but this galectin cannot be detected in the blood of HNSCC patients. Galectin-3 levels differ significantly (p=0.03) in healthy volunteers and HNSCC patients. Using a threshold value of 4.3 ng/ml, galectin-3 serum level enabled a significant level of discrimination (p=0.03) to be established between the cancer patients and the healthy volunteers, with 90% level of specificity and 36% level of sensitivity. The discrimination was even better when using a threshold value of 13.5 ng/ml for galectin-1 (p=0.001), with 100% level of specificity and 22% level of sensitivity. A subgroup of stage IV HNSCC patients displayed significantly reduced levels of circulating galectin-1 (p=0.003) and galectin-3 (p=0.001) after treatment as opposed to before. Galectin-3 concentrations in sera from the patients with a metastatic disease were significantly (p=0.01) higher than in sera from the patients with localized tumors. The determination of circulating levels of galectin-1 and -3 could be used to monitor the progression of their disease or their response to therapy. PMID- 17350329 TI - The anti-mutagenic and antioxidant effects of bile pigments in the Ames Salmonella test. AB - The aim of this study was to explore the potential pro- and anti-mutagenic effects of endogenous bile pigments unconjugated bilirubin (BR), biliverdin (BV) and a synthetic, water soluble conjugate, bilirubin ditaurate (BRT) in the Ames Salmonella test. The bile pigments were tested over a wide concentration range (0.01-2 micromol/plate) in the presence of three bacterial strains (TA98, TA100, TA102). A variety of mutagens including benzo[alpha]pyrene (B[alpha]P), 2,4,7 trinitrofluorenone (TNFone), 2-aminofluorene (2-AF), sodium azide (NaN(3)) and tertiary-butyl hydroperoxide (t-BuOOH), were used to promote the formation of mutant revertants. Tests were conducted with (B[alpha]P, 2-AF, t-BuOOH) and without (TNFone, NaN(3), t-BuOOH) metabolic activation incorporating the addition of the microsomal liver preparation, S9. The bile pigments alone did not induce mutagenicity in any of the strains tested (p>0.05). Anti-mutagenic effects of the bile pigments were observed in the presence of all mutagens except for NaN(3) and the anti-mutagenic effects appeared independent of the strain tested. For TNFone induced genotoxicity, the order of effectiveness was BR> or =BRT>BV. However, the order was BV> or =BRT> or =BR for 2-AF. Antioxidant testing in the TA102 strain revealed bile pigments could effectively inhibit the genotoxic effect of t-BuOOH induced oxidative stress. The apparent antioxidant and anti-mutagenic behaviour of bile pigments further suggests their presence in biological systems is of possible physiological importance. PMID- 17350330 TI - Effect of Ga2O3 on the spectroscopic properties of erbium-doped boro-bismuth glasses. AB - The spectroscopic properties and thermal stability of Er3+-doped Bi2O3-B2O3-Ga2O3 glasses are investigated experimentally. The effect of Ga2O3 content on absorption spectra, the Judd-Ofelt parameters Omega t (t=2, 4, 6), fluorescence spectra and the lifetimes of Er3+:4I 13/2 level are also investigated, and the stimulated emission cross-section is calculated from McCumber theory. With the increasing of Ga2O3 content in the glass composition, the Omega t (t=2, 4, 6) parameters, fluorescence full width at half maximum (FWHM) and the 4I 13/2 lifetimes of Er3+ first increase, reach its maximum at Ga2O3=8 mol.%, and then decrease. The results show that Er3+-doped 50Bi2O3-42B2O3-8Ga2O3 glass has the broadest FWHM (81nm) and large stimulated emission cross-section (1.03 x1 0( 20)cm2) in these glass samples. Compared with other glass hosts, the gain bandwidth properties of Er+3-doped Bi2O3-B2O3-Ga2O3 glass is better than tellurite, silicate, phosphate and germante glasses. In addition, the lifetime of 4I 13/2 level of Er(3+) in bismuth-based glass, compared with those in other glasses, is relative low due to the high-phonon energy of the B-O bond, the large refractive index of the host and the existence of OH* in the glass. At the same time, the glass thermal stability is improved in which the substitution of Ga2O3 for B2O3 strengthens the network structure. The suitability of bismuth-based glass as a host for a Er3+-doped broadband amplifier and its advantages over other glass hosts are also discussed. PMID- 17350331 TI - Non-invasive predictors of survival in cardiac amyloidosis. AB - BACKGROUND: Patients with cardiac amyloidosis (CA) have increased mortality. AIMS: Clinical, electrocardiographic, and echocardiographic parameters were assessed for risk-stratification of CA. METHODS AND RESULTS: CA was confirmed by endomyocardial biopsy in 59 patients (54.8+/-1.2 years) with light-chain (n = 43) or transthyretin amyloidosis (n = 16). Six patients without CA served as controls (NCA). Clinical symptoms, electrocardiographic, and echocardiographic parameters were analyzed for prognostic significance. Of the patients with light-chain amyloidosis, 14 died and 2 underwent heart transplantation. 1-/3-year survival was 68%/63%. Survival depended on left ventricular function (LV-EF), LV mass, radius/wall thickness, septum thickness, low voltage pattern (LVP), conduction delay, NYHA class, and stem cell transplantation. A multivariate model only contained LV-EF and LVP; the beneficial effect of stem cell transplantation was cancelled out as this treatment was withheld in patients with highest cardiac risk. Survival was most limited if both risk factors occurred. Cardiac involvement in transthyretin amyloidosis showed better survival (2 deaths, 1-/3 year survival 91%/83%). Analysis of prognostic risk factor utility in all amyloid patients (light-chain and transthyretin) again revealed LVP and LV-EF, and aetiology of amyloidosis as independent survival parameters. CONCLUSION: Prognosis of CA is poor, but aetiology of amyloid, LVP, and LV-EF allows identification of patients at highest risk of death, who may require individual treatment approaches (heart transplantation prior to causative therapy). PMID- 17350332 TI - The contribution of efflux pumps to quinolone resistance in Streptococcus pneumoniae clinical isolates. AB - Active efflux has been involved in fluoroquinolone resistance in Streptococcus pneumoniae. While only one efflux machinery has been well described (PmrA), the eventual existence of other pumps than PmrA has been suggested. The actual role of active quinolone efflux in producing ciprofloxacin resistance was examined by means of several methods. Strains HUB 2375 and HUB 3073 are clinical isolates resistant to fluoroquinolones. Since no mutations in the quinolone resistance determining regions of these strains were found, resistance to fluoroquinolones should be attributed only to efflux. Strain R6 was transformed by DNA from both HUB 2375 and HUB 3073. Selected transformants were chosen for knockout of pmrA genes by polymerase chain reaction ligation mutagenesis in order to study the actual role and the degree of involvement of PmrA in determining ciprofloxacin resistance. Results strongly supported the hypothesis that efflux pumps other than PmrA are involved in fluoroquinolone resistance in clinical strains of pneumococci. PMID- 17350333 TI - Towards an empirical model of performance enhancing supplement use: a pilot study among high performance UK athletes. AB - This paper addressed a gap in the literature of empirically derived models of performance enhancing supplement use by developing a demographic and psychosocially based model of athlete supplement use. Selected questions were used from a larger survey conducted by UK Sport into British athletes' experiences, knowledge, attitudes and opinions in relation to anti-doping activities. Forward conditional step wise logistic regression was employed on data from n=757 athletes to develop a model that discriminated supplement non users from users. The model identified that British athletes most likely to use supplements were younger (under 23) males who were more likely to see doping as a problem in their sport and were more knowledgeable about testing procedures than their non-user counterparts. Post hoc analysis reinforced that non-users saw doping as less of a problem in their sport and were less knowledgeable about drug testing procedures relative to those using supplements. The pattern of results indicated gender-specific interventions on supplement use for young male athletes may yield significant benefits. The relationship between supplement use and perception of a doping problem suggested more work is needed to understand supplement use culture within sports. The relationship between knowledge of testing procedures and supplement use suggested further research is needed to see whether this is a positive or negative effect of detection-based doping deterrence activity. PMID- 17350334 TI - Changes in markers of muscle damage of middle-aged and young men following eccentric exercise of the elbow flexors. AB - It is well documented that unaccustomed eccentric exercise induces muscle damage, but the responses of middle-aged individuals to a bout of eccentric exercise have not been reported. The purpose of this study was to compare changes in indirect markers of muscle damage following eccentric exercise of the elbow flexors between 12 young (age: 19.4+/-0.4 years, height: 173.5+/-2.0cm, body mass: 65.8+/ 3.5kg) and 12 middle-aged men (48.0+/-2.1 years, 169.5+/-1.7cm, 67.3+/-1.6kg). It was hypothesized that middle-aged men would be more susceptible to muscle damage than young men. All subjects performed six sets of five eccentric actions of the elbow flexors using a dumbbell of 40% of maximal isometric strength (MVC). Changes in MVC, elbow joint angles and range of motion, upper arm circumference, plasma creatine kinase activity and myoglobin concentration, and muscle soreness before, immediately after, and 1, 2, 3, and 4 days after exercise were compared between the young and middle-aged groups by a two-way repeated measures ANOVA. All criterion measures changed significantly (P<0.05) after exercise, but no significant differences in the changes in the measures except for muscle soreness were evident between groups. Development of muscle soreness after exercise was significantly (P<0.05) lower (approximately a half of the value) for the middle aged group compared with the young group. These results did not support the hypothesis that middle-aged men would be more susceptible to muscle damage than young men. PMID- 17350335 TI - Giant morgagni hernia causing cardiac tamponade. AB - A 57-year-old man presented with worsening symptoms of shortness of breath and chest pain. He was found to have a giant Morgagni hernia with severe compression of his right ventricle on computed tomography scan. The hernia which contained greater omentum, small intestine and transverse colon was urgently repaired through a median sternotomy and laparotomy with a polypropylene mesh. Morgagni hernia is a type of congenital diaphragmatic hernia, which may not be symptomatic until adulthood. Presentation with this degree of right ventricular compression is rare. PMID- 17350337 TI - Palmar-plantar erythrodysesthesia (PPE): a literature review with commentary on experience in a cancer centre. AB - Palmar-plantar erythrodysesthesia (PPE) or hand-foot syndrome (HFS) is a relatively common side effect of cytotoxic chemotherapy. Many cytotoxic drugs have been reported to cause the condition but it is more frequently associated with 5 fluorouracil (5FU), liposomal doxorubicin and cytarabine. The oral 5FU precursor, capecitabine is frequently associated with PPE and with the recent extension of its use to adjuvant treatment, the incidence of PPE is likely to increase. The initial symptoms are dysesthesia and tingling in the palms, fingers and soles of feet and erythema, which may progress to burning pain with dryness, cracking, desquamation, ulceration and oedema. Palms of the hands are more frequently affected than soles of the feet. This condition is painful and distressing to patients and in some incidences it results in patients not being able to work or perform normal daily activities. It can also result in treatment interruptions which impact on the efficacy of the treatment regimen. Effective and appropriate patient education from a specialist nurse prior to treatment is an essential part of patient management which will facilitate early identification of the symptoms and therefore prevent treatment delays and PPE progression. This article reviews current knowledge of the condition, including classification, and discussion of the findings of a clinical audit in a cancer centre. It includes the incidence, grading, management and impact of PPE on normal daily activities. PMID- 17350338 TI - Transcription and coregulation of multigene families in Plasmodium falciparum. AB - Subtelomeric regions in the Plasmodium genome are enriched with members of three major multigene families: var, rif and stevor. In this article, we discuss a recent study by Sharp and colleagues that focused on the transcribed repertoire of var and stevor genes in asexual and sexual Plasmodium parasites. Transcription of these two multigene families seems to be unlinked in asexual parasites. Parasites in the gametocyte stages transcribe members of the upsC subset of var genes, which indicates the intriguing possibility of their involvement in gametocyte adhesion. PMID- 17350339 TI - Research and control of parasitic diseases in Japan: current position and future perspectives. AB - Between 1950 and 1980, Japan eliminated several major parasitic diseases. In 1998, the Japanese Hashimoto Initiative was the first global programme to target parasitic diseases. Thereafter, Japan expanded its international cooperation to cover infectious diseases through integrated development programmes to improve health, to alleviate poverty and to help to achieve the Millennium Development Goals of the United Nations. Parasite control remains a major component of all subsequent operations. Opportunities to build upon past successes in order to improve the situation in the developing world - in addition to tackling emerging national threats - are promising. Substantial challenges remain and Japan has introduced major national reforms to try to overcome them. PMID- 17350340 TI - Whole-genome natural histories of apicomplexan surface proteins. AB - The natural histories of free-living and pathogenic protozoans have been described in over a century of studies, spanning a range of disciplines such as microscopic, cellular, taxonomic, pathological, clinical and molecular. Only in the last decade has this landscape of work benefited from the availability of whole-genome nucleotide sequence data. For many pathogens, it is now possible to overlay analyses of protein repertoires onto the current spectrum of knowledge. This article illuminates protozoan natural histories, particularly the rapidly evolving and highly adaptive direct physical interface of apicomplexan parasites and their hosts, by providing a brief introduction to the origin and phylogenetic distribution of parasite-encoded surface proteins and their component domains. PMID- 17350341 TI - HBV-encoded microRNA candidate and its target. AB - MicroRNAs (miRNAs) are a group of short (approximately 22 nt) noncoding RNAs that specifically regulate cellular gene expression at the post-transcriptional level. miRNA precursors (pre-miRNAs), which are imperfect stem loop structures of approximately 70 nt, are processed into mature miRNAs by cellular RNases III. To date, hundreds of miRNAs and their corresponding targets have been reported in kinds of species. Although only a few of these miRNA/target pairs have been functionally verified, some do play important roles in regulating normal development and physiology. Several viruses (e.g. the Epstein-Barr virus and human herpesvirus Kaposi's sarcoma-associated herpesvirus) has been reported to encode miRNAs. Here, we extend the analysis of miRNA-encoding potential to the Hepatitis B virus (HBV). Using computational approaches, we found that HBV putatively encodes only one candidate pre-miRNA. We then matched deduced mature miRNA sequence from this pre-miRNA against a database of 3' untranslated sequences (UTR) from the human genome. Surprisingly, none of cellular transcripts could potentially be targeted by the viral miRNA (vmiRNA) sequence. However, one viral mRNA was found to be targeted by the vmiRNA when we searched the target from viral mRNAs. We propose that HBV has evolved to use vmiRNAs as a means to regulate its own gene expression for its benefit. PMID- 17350342 TI - Slight improvement in mood and irritability after antiepileptic drug withdrawal: a controlled study in patients on monotherapy. AB - OBJECTIVE: Most antiepileptic drugs (AEDs) are considered to have effects on mood and to be effective in a number of affective disorders. There are, however, conflicting reports in the literature with respect to the psychotropic properties of AEDs. Many of the studies have a number of methodological problems, and much uncertainty still exists regarding the behavioral and mood effects of AEDs. The aim of this study was to assess, in a randomized, double-blind, placebo controlled study of seizure-free patients with epilepsy, the effect of withdrawal of AEDs in patients on monotherapy on measures of mood and behavior. METHODS: One hundred fifteen subjects who had been seizure-free >2 years on drug monotherapy went through a randomized, double-blind, placebo-controlled study. Each patient was included for 12 months or until seizure relapse. Behavioral function was assessed with the Minnesota Multiphasic Personality Inventory 2 (MMPI-2) at baseline and 7 months after withdrawal. RESULTS: Discontinuation of AEDs resulted, to a greater extent than continued treatment, in a slight improvement in symptoms of depression and irritability. Comparable results were achieved in the subgroup taking carbamazepine. For patients with a high degree of depressive and somatic symptoms at baseline, no significant differences in symptoms emerged in the withdrawal group compared with the non-withdrawal group. CONCLUSION: The results suggest that seizure-free patients with epilepsy on monotherapy can obtain a slight improvement in symptoms characteristic of depression and irritability if they discontinue treatment with AEDs. The described changes are limited, and the functional impact is of uncertain significance. PMID- 17350343 TI - Protective effect of modified glucomannans and organic selenium against antioxidant depletion in the chicken liver due to T-2 toxin-contaminated feed consumption. AB - The aim of this work was to assess the effect of T-2 toxin on the antioxidant status of the chicken and to study possible protective effects of modified glucomannan (Mycosorb) and organic selenium (Sel-Plex). Inclusion of T-2 toxin in the chickens' diet (8.1 mg/kg for 21 days) was associated with significant decreases in the concentrations of selenium (Se)(by 32.2%), alpha-tocopherol (by 41.4%), total carotenoids (by 56.5%), ascorbic acid (by 43.5%) and reduced glutathione (by 56.3%) in the liver, as well as a decrease in the hepatic activity of Se-dependent glutathione peroxidase (Se-GSH-Px) (by 36.8%). However, inclusion of modified glucomannans into the T-2 toxin-contaminated diet provided a partial protection against the detrimental effects of the mycotoxin on the antioxidant defences in the chicken liver. For example, the Se concentration in the liver was restored completely, although the Se-GSH-Px activity in the liver increased to only 81% of its control value. These protective effects of modified glucomannas were associated with a 45% reduction of lipid peroxidation in the liver in comparison to the effects of T-2 toxin alone. A combination of modified glucomannas with organic Se was shown to provide further protection against toxin induced antioxidant depletion and lipid peroxidation in the chicken liver. Thus, the data clearly indicate a major protective effect of the mycotoxin-binder in combination with organic Se against the detrimental consequences of T-2 toxin contaminated feed consumption by growing chickens. PMID- 17350344 TI - Sterol demethylation inhibitor fungicides as disruptors of insect development and inducers of glutathione S-transferase activities in Mamestra brassicae. AB - To study physiological and biochemical effects of demethylation inhibitor (DMI) fungicides on non-target insects, larvae of the cabbage moth, Mamestra brassicae L., were exposed orally to propiconazole, (R,S)-1-[2-(2,4-diclophenyl)-4-propyl 1,3-dioolan-2-ylmetyl]-1H-1,2,4-triazole (100, 200 and 600 mg L(-1)) and fenpropimorph, (+/-)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl] 2,6 dimethylmorpholinc (10, 100, 200 and 600 mg L(-1)) in a semi-synthetic diet. Ten mg L(-1) of fenpropimorph reduced larval weight and induced in vitro glutathione S-transferase activity. Reduced larval and pupal growth rate, reduced survival, prolonged developmental time, and altered patterns of larval survival and adult emergence were found for one or both fungicides in at least one of the concentrations tested. The results suggest, that although the use of agricultural fungicides is generally regarded as of minor ecotoxicological consequence for insects, feeding on DMI-treated crops may influence insect fitness, and may also leave them susceptible to pesticide treatments or to residues of pesticides and other pollutants in their food. Standard methods to detect such effects should be developed for use in the environmental risk assessment of these products. PMID- 17350345 TI - Trace metal burdens and expression of heat stable low molecular mass proteins in the female asteroid Coscinasterias muricata--Fluctuations throughout the reproductive cycle. AB - Concentrations of the essential trace metals copper and zinc were measured in the pyloric caeca of female Coscinasterias muricata sampled from Port Phillip Bay, Victoria, Australia at monthly intervals for 15 months. Results indicate that the concentrations of these metals appear to be regulated by the reproductive cycle. Peaks in zinc concentration occurred simultaneously with peaks in progesterone concentration in the pyloric caeca. These findings suggest that zinc plays a role in gametogenesis and ovarian development. Fluctuations in pyloric caeca copper concentration appear inversely related to the pyloric caecal index and associated with oocyte diameter, indicative of a role for this metal in oogenesis. The levels of cytosolic heat stable low molecular mass (LMM) proteins were examined throughout the sampling period. Heat stable LMM proteins (metallothionein-like) of 12 kDa and 7.5 kDa (apparent molecular mass) and the concentrations of copper appear to be related; although the exact nature of these proteins remains unknown. No such relationship was observed between the levels of heat stable LMM proteins and zinc. PMID- 17350346 TI - Screening and secretomic analysis of enthomopatogenic Beauveria bassiana isolates in response to cowpea weevil (Callosobruchus maculatus) exoskeleton. AB - The production of cowpea (Vigna unguiculata), an important self-sustained crop in Latin America and Africa, is severely affected by damage by the cowpea weevil Callosobruchus maculatus. The presence of a single larva in stored seeds can lead to losses of almost 40%. Control of C. maculatus currently relies on the inefficient use of chemical insecticides and post-harvest treatments. The use of entomopathogenic fungus became a reliable alternative for coleopteran pest control and has been extensively investigated. Among them, Beauveria bassiana and Metarhizium anisopliae were widely evaluated in order to measure their virulence toward many insects. In this report, we evaluated the insecticidal activity of ten strains of B. bassiana and the most lethal fungi strains were analyzed for proteinaceous secretions by two dimensional electrophoresis and for enzyme activities, including chitinolytic, proteolytic and alpha-amylolytic activities. This study could, in the near future, help to establish novel biotechnological tools to use for cowpea weevil control. PMID- 17350347 TI - Relationship between sympathetic nerve sprouting and repolarization dispersion at peri-infarct zone after myocardial infarction. AB - Sympathetic nerve sprouting is thought to contribute to sudden cardiac death (SCD) in chronic myocardial infarction (MI). However, the mechanisms remain unclear. This study investigated the relationship between sympathetic nerve sprouting and repolarization dispersion at peri-infarct zones after MI. Thirty adult New Zealand White rabbits underwent coronary artery ligation (MI group: n=20) or sham operation (SO group: n=10). Eight weeks after surgery, transmural dispersion of repolarization (TDR) was examined at the peri-infarct zones in MI group and corresponding zones in the SO group at baseline and during sympathetic nerve stimulation. Sympathetic nerve sprouting was detected by immunocytochemical staining using anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. The results demonstrated that TDR was significantly larger at peri-infarct zones in MI group than the corresponding zone in SO group at baseline or during sympathetic nerve stimulation. The densities of both GAP43- and TH-positive nerves were significantly higher at peri-infarct zones in infracted hearts than the corresponding zones in control hearts (both p<0.01). In the MI group, the density of GAP43- or TH-positive nerves at peri-infarct zones had a significantly positive correlation with the TDR or DeltaTDR (change in TDR) at baseline as well as with sympathetic nerve stimulation (p<0.05 for all). These results suggested that sympathetic nerve sprouting is more pronounced and heterogeneous at peri-infarct zones at 8 weeks after MI. The excessive sprouting of sympathetic nerves increases local ventricular TDR, which may be a potential mechanism for SCD in chronic MI. PMID- 17350349 TI - Ciliary band gene expression patterns in the embryo and trochophore larva of an indirectly developing polychaete. AB - The trochophore larvae of indirectly developing spiralians have ciliary bands with motor and feeding functions. The preoral prototroch ciliary band is the first differentiating organ in annelid and mollusk embryos. Here we report the expression of several ciliary band markers during embryogenesis and early larval stages of the indirectly developing polychaete Hydroides elegans. Genes with similarity to caveolin, beta-tubulin, alpha-tubulin, and tektin are expressed in the eight primary prototroch precursors, 1q(221) and 1q(212). Blastomeres 1q(221) and 1q(212) locate at the same equatorial latitude after the complementary asymmetric division of their 1q(22) and 1q(21) precursors. In addition, caveolin and alpha-tubulin are expressed in the metatroch and adoral ciliary zone. Caveolin is expressed in foregut ciliated cells, and alpha-tubulin is expressed in apical tuft ciliated cells. The expression of a beta-thymosin homolog is restricted to 1q(122) and 1q(121) blastomeres, which locate just above and in close association with the eight primary prototroch cells 1q(221) and 1q(212). In addition, the beta-thymosin homolog has a transient expression in the hindgut and apical zone. The expression of all these genes provides a landmark for the early specification of ciliary bands and other ciliated organs. PMID- 17350350 TI - DengueInfo: A web portal to dengue information resources. AB - DengueInfo (http://www.dengueinfo.org) is a web portal and database that brings clarity to dengue research by integrating the growing number of complete genome sequences of dengue virus with relevant literature and curated epidemiological information. Additionally, it represents a repository of on-going prospective and retrospective studies of dengue disease severity. We intend the database to be a flagship resource for the dengue community, providing standardized and high quality information and facilitating research into key aspects of dengue biology and assisting in its control. To aid this process we also introduce a standard nomenclature for dengue isolates inspired by globally accepted system used for influenza virus. PMID- 17350348 TI - Parasympathetic control of airway submucosal glands: central reflexes and the airway intrinsic nervous system. AB - Airway submucosal glands produce the mucus that lines the upper airways to protect them against insults. This review summarizes evidence for two forms of gland secretion, and hypothesizes that each is mediated by different but partially overlapping neural pathways. Airway innate defense comprises low level gland secretion, mucociliary clearance and surveillance by airway-resident phagocytes to keep the airways sterile in spite of nearly continuous inhalation of low levels of pathogens. Gland secretion serving innate defense is hypothesized to be under the control of intrinsic (peripheral) airway neurons and local reflexes, and these may depend disproportionately on non-cholinergic mechanisms, with most secretion being produced by VIP and tachykinins. In the genetic disease cystic fibrosis, airway glands no longer secrete in response to VIP alone and fail to show the synergy between VIP, tachykinins and ACh that is observed in normal glands. The consequent crippling of the submucosal gland contribution to innate defense may be one reason that cystic fibrosis airways are infected by mucus-resident bacteria and fungi that are routinely cleared from normal airways. By contrast, the acute (emergency) airway defense reflex is centrally mediated by vagal pathways, is primarily cholinergic, and stimulates copious volumes of gland mucus in response to acute, intense challenges to the airways, such as those produced by very vigorous exercise or aspiration of foreign material. In cystic fibrosis, the acute airway defense reflex can still stimulate the glands to secrete large amounts of mucus, although its properties are altered. Importantly, treatments that recruit components of the acute reflex, such as inhalation of hypertonic saline, are beneficial in treating cystic fibrosis airway disease. The situation for recipients of lung transplants is the reverse; transplanted airways retain the airway intrinsic nervous system but lose centrally mediated reflexes. The consequences of this for gland secretion and airway defense are poorly understood, but it is possible that interventions to modify submucosal gland secretion in transplanted lungs might have therapeutic consequences. PMID- 17350351 TI - Electric field modulation in tissue electroporation with electrolytic and non electrolytic additives. AB - Electroporation, cell membrane permeabilization with short electrical field pulses, is used in tissue for in vivo gene therapy, drug therapy and minimally invasive tissue ablation. For the electroporation to be successful, the electrical field that develops during the application of the pulses needs to be precisely controlled. In this study we investigate the use of electrolytic and non-electrolytic gels to generate the precise electrical fields required for controlled electroporation, in heterogeneous and irregular tissues, in vivo. Finite element computer simulations are used to illustrate various applications, such as the treatment of irregularly shaped organs and interior cavities. The feasibility of the concept is demonstrated experimentally in vivo with a rat liver subjected to irreversible electroporation. PMID- 17350352 TI - Conducting polymers in modelling transient potential of biological membranes. AB - The possibility of using conducting polymer (CP) films doped with biological ligands as artificial biological membranes to study potential formation mechanisms is presented. Calcium and magnesium ion-binding anionic sites- asparagine, glutamine, adenosinotriphosphate and heparin are incorporated into the poly(pyrrole) film during electrochemical polymerization. This approach allows the competitive calcium-magnesium ion-exchange to be inspected by open circuit measurements. After a close-to-Nernstian sensitivity of the CP membranes was induced by soaking in alkaline solutions of calcium or magnesium, dynamic experiments were performed by a change in the bulk concentration of magnesium or calcium ions. A characteristic transitory potential response, though distinctively different for the calcium and magnesium ions, was observed and explained using the diffusion layer model (DML). PMID- 17350353 TI - Association of HLA genes with diffuse panbronchiolitis in Chinese patients. AB - Diffuse panbronchiolitis (DPB) is a pulmonary disease of unknown etiology that predominantly affects East Asians, particularly Japanese with a prevalence of 0.00028. Research has shown that HLA-B54 and HLA-A11 are positively associated with this disease. HLA-A, -B, and -DR loci were analyzed using an oligonucleotide microarray in both Chinese patients with DPB and normal control subjects. The most marked difference between the patients and the controls was the decreased frequency of HLA-A2 (p=0.001, OR=0.12), which showed a negative association with the disease; however, there was no significant contribution of HLA-B loci. Interestingly, the frequency of HLA-A11 was increased (p=0.007, OR=3.9), in accordance with previous reports on Japanese and Koreans. In addition, the frequency of HLA-DRB5*010/020 slightly increased (p=0.049). The HLA-associated genes for DPB are located between the HLA-A and HLA-B loci. Differences in HLA associated genes may partially explain differences in the incidence of DPB among different populations. PMID- 17350354 TI - Enantioselective determination of azelnidipine in human plasma using liquid chromatography-tandem mass spectrometry. AB - A sensitive and simple method was developed for determination of the enantiomers of azelnidipine, (R)-(-)-azelnidipine and (S)-(+)-azelnidipine, in human plasma using chiral liquid chromatography with positive ion atmospheric pressure chemical ionization tandem mass spectrometry. Plasma samples spiked with stable isotope-labeled azelnidipine, [(2)H(6)]-azelnidipine, as an internal standard, were processed for analysis using a solid-phase extraction in a 96-well plate format. The azelnidipine enantiomers were separated on a chiral column containing alpha(1)-acid glycoprotein as a chiral selector under isocratic mobile phase conditions. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode, monitoring the transitions from m/z 583-->167 for (R)-( )-azelnidipine and (S)-(+)-azelnidipine, and from m/z 589-->167 for [(2)H(6)] azelnidipine. The standard curve was linear over the studied range (0.05-20 ng/mL), with r(2)>0.997 using weighted (1/x(2)) quadratic regression, and the chromatographic run time was 5.0 min/injection. The intra- and inter-assay precision (coefficient of variation), calculated from the assay data of the quality control samples, was 1.2-8.2% and 2.4-5.8% for (R)-(-)-azelnidipine and (S)-(+)-azelnidipine, respectively. The accuracy was 101.2-117.0% for (R)-(-) azelnidipine and 100.0-107.0% for (S)-(+)-azelnidipine. The overall recoveries for (R)-(-)-azelnidipine and (S)-(+)-azelnidipine were 71.4-79.7% and 71.7-84.2%, respectively. The lower limit of quantification for both enantiomers was 0.05 ng/mL using 1.0 mL of plasma. All the analytes showed acceptable short-term, long term, auto-sampler and stock solution stability. Furthermore, the method described above was used to separately measure the concentrations of the azelnidipine enantiomers in plasma samples collected from healthy subjects who had received a single oral dose of 16 mg of azelnidipine. PMID- 17350355 TI - In vitro and in vivo degradability and cytocompatibility of poly(l-lactic acid) scaffold fabricated by a gelatin particle leaching method. AB - Porous poly(l-lactic acid) (PLLA) scaffolds fabricated by a gelatin particle leaching technique have good mechanical property and cytocompatibility, as demonstrated by a previous in vitro study. Here we investigate further the in vitro degradation of the scaffolds in terms of weight loss, water uptake, weight average molecular weight, thermal behavior and morphology during a 39 week period in phosphate-buffered saline. The water uptake decreased dramatically during the initial stage due to release of the remaining gelatin, and then increased slightly with degradation time. The weight-average molecular weight decreased linearly as a function of time, while the crystallinity steadily increased with slightly decreased melting temperature. After degradation, many defects and big holes were seen in the scaffolds by scanning electron microscopy. Cartilage regeneration and scaffold disappearance in vivo were compared by implanting the construct into nude mice for 30-120 days. While the scaffolds maintained their intact pore structure after 23 weeks of degradation in vitro, they almost disappeared in vivo at the same time, implying a faster degradation rate in vivo. By 120 days after implantation, the scaffolds were hardly seen in the newly formed cartilage-like tissue. The regenerated cartilages could not maintain their predesigned shape after a long period of in vivo culture due to the weakening of the mechanical strength of the constructs as a result of PLLA degradation. The regions occupied initially by PLLA scaffold were filled later by collagen type II secreted by the chondrocytes, but with no evident basophilic proteoglycan. PMID- 17350356 TI - Clinical trials in neonates: ethical issues. AB - If neonates are to receive the best possible treatment, they must be involved in clinical trials. However, doing such trials raises complicated ethical issues. These issues are not unique to neonatology but some are more common or acute than in other areas of medicine. In practice, two particular issues -- equipoise and informed consent -- arise as many different types of problem. The question 'What is an ethical issue?' is important because issues that are not ethical are sometimes mistakenly thought to be so, and vice versa. When we can recognize what types of problem are ethical, we can also recognize the correct means to tackle them. PMID- 17350357 TI - Mineralized tissue cells are a principal source of FGF23. AB - While fibroblast growth factor (FGF) 23 is known as a phosphaturic factor in inherited and/or acquired hypophosphatemic disorders, it also serves an endocrine role in normal phosphate homeostasis. FGF23 acts negatively on the NaPi2a cotransporter and 25-hydroxy D(3)-1 alpha-hydroxylase with a resultant decrease in renal phosphate (Pi) reabsorption, while osteoblasts appear to be a primary source of FGF23 whose expression is counter-upregulated by 1 alpha,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Here we have shown the distribution of FGF23 in normal rat bone and tooth, and its expression profile in fetal rat calvaria (RC) cell cultures. FGF23 mRNA was detectable in multiple fetal and adult tissues but levels were much higher in adult calvaria, femur and incisor, compared to the other tissues tested. Immunoreactive FGF23 was predominantly localized to osteoblasts, cementoblasts, and odontoblasts, with sporadic labeling in some chondrocytes, osteocytes and cementocytes. Notably, osteoclasts were also found to be a possible source of FGF23. Fetal bone and tooth germ cells labeled much less intensely than young adult osteoblasts and odontoblasts. In the RC cell model, FGF23 was expressed during osteoblast development. During matrix mineralization induced by beta-glycerophosphate (beta GP), FGF23 expression was transiently upregulated and then decreased to levels lower than in their non-beta GP-treated counterparts. 1,25(OH)(2)D(3) markedly increased FGF23 expression concomitant with the inhibition of beta GP-induced mineralization. Our data suggest that FGF23 expression in bone is closely correlated with bone formation in vitro and vivo, and points towards an important role(s) for FGF23 in young adult but not fetal mineralized tissues as a systemic factor for Pi homeostasis. PMID- 17350358 TI - Recent trends in hospital utilization for acute myocardial infarction and coronary revascularization in the United States. AB - Medical advances may be shifting patients with coronary artery disease away from the hospital setting despite an aging United States population. We explored this possibility using national inpatient data to estimate the number and population based rates of hospitalization for acute myocardial infarction (AMI) and coronary revascularization from 2002 to 2005. Our primary data source was the Acute Care Tracker database, a proprietary administrative database that contains data on approximately 6 million discharges per year from 458 hospitals across the United States. Using the Acute Care Tracker database, we estimated the annual number and population-based rates of hospitalization for AMI (transmural, subendocardial) and coronary revascularization (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). Hospitalizations for AMI steadily decreased from 661,000 to 591,000 per year between 2002 and 2005, primarily due to decreases in transmural AMI. Hospitalizations for coronary revascularizations during this period varied between 794,000 and 815,000 per year, with the number of PCIs increasing and the number of CABGs decreasing. In addition, rates of hospitalization for AMI decreased from 309 to 266 per 100,000 persons between 2002 and 2005, with rates of transmural AMI decreasing substantially from 118 to 87 per 100,000 persons. Rates of hospitalization for coronary revascularization also decreased from 382 to 358 per 100,000 during this period, primarily due to decreases in CABG. In conclusion, the number and rates of hospitalization for AMI and coronary revascularization in the United States are decreasing. PMID- 17350359 TI - Usefulness of ultrasonic strain measurements to predict regional wall motion recovery in patients with acute myocardial infarction after percutaneous coronary intervention. AB - Strain Doppler echocardiography can detect systolic regional myocardial dysfunction. This study assessed whether strain could predict recovery of regional left ventricular function in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention. Forty-three patients with anterior AMI undergoing successful percutaneous coronary intervention of the left anterior descending coronary artery were studied. Longitudinal myocardial strain was measured at the left anterior descending coronary artery territory in the apical long-axis view within 24 hours after percutaneous coronary intervention. Regional wall motion was analyzed by the anterior wall motion score index (A WMSI). Viable myocardium was defined as a decrease < or = 2.0 in A-WMSI. Patients were categorized as A-WMSI at 4 weeks into a viable group (n = 24) and a nonviable group (n = 19). End-systolic strain and peak strain were significantly lower in the nonviable group than in the viable group (-4.8 +/- 4.8% vs -9.9 +/- 4.7 %, p <0.005; -9.9 +/- 4.6 vs -13.5 +/- 4.1 %, p <0.05). Moreover, corrected time to peak strain (cTPS; time delay from end-systolic to peak strain/RR interval) was significantly longer in the nonviable group than in the viable group (0.19 +/- 0.04 vs 0.13 +/- 0.03, p <0.0001). For prediction of viable myocardium, cTPS <0.15 had a sensitivity of 95% and a specificity of 85%. In conclusion, strain, especially cTPS, is useful for predicting recovery of regional left ventricular function in patients with AMI after percutaneous coronary intervention. PMID- 17350360 TI - Results and predictors of angiographic restenosis and long-term adverse cardiac events after drug-eluting stent implantation for aorto-ostial coronary artery disease. AB - The correlates of angiographic and clinical outcomes after drug-eluting stent (DES) implantation for aorto-ostial lesions remain unknown. This study evaluated long-term results of DES implantation for aorto-ostial lesions and determined risk factors for restenosis and adverse cardiac events. In total, 184 consecutive patients who underwent DES implantation for aorto-ostial lesions were investigated (DES group) compared with 172 consecutive patients treated with bare metal stents before the introduction of DESs (pre-DES group). Major adverse cardiac events (MACEs) were defined as death, Q-wave myocardial infarction, and need for target lesion revascularization. The DES group had significantly higher risk clinical and procedural profiles than the pre-DES group. Procedural success rates were 99.5% in the DES group and 100% in the pre-DES group (p = 1.0). The DES group had a significantly lower incidence of in-segment restenosis (10.5% vs 26.0%, p = 0.001) and target lesion revascularization (4.3% vs 11.6%, p = 0.011). Cumulative MACE rates at 1 year were 6.5% in the DES group and 13.4% in the pre DES group (p = 0.03). By multivariate analysis, treatment of bypass graft, treatment of in-stent restenosis, and reference vessel diameter were predictors of restenosis, and only reference vessel diameter (hazard ratio 0.20, 95% confidence interval 0.05 to 0.75, p = 0.017) inversely correlated with 1-year MACEs after DES implantation. In conclusion, DES implantation for aorto-ostial lesions is associated with a significant decrease in restenosis and MACEs compared with the pre-DES phase. Treatment of bypass graft and in-stent restenosis and reference vessel size were identified as predictors of restenosis and/or long-term MACEs after DES implantation. PMID- 17350362 TI - Elective high-risk percutaneous coronary interventions supported by extracorporeal life support. AB - This study investigated the feasibility of high-risk percutaneous coronary intervention (PCI) in hemodynamically unstable patients supported by modified cardiopulmonary bypass (extracorporeal life support [ELS]). Over a 38-month period, 15 patients (10 men, 5 women, mean age 72 +/- 9 years, mean ejection fraction 34 +/- 15%, angina pectoris New York Heart Association class III to IV) who were not eligible for coronary artery bypass grafting because of high co morbidity underwent elective high-risk PCI supported by ELS. All lesions were technically challenging. ELS perfusion cannulas in the femoral artery and vein were surgically inserted and removed. Procedural success was achieved in 14 of 15 patients. After a mean perfusion duration of 88 +/- 37 minutes, all patients were weaned from the ELS in the catheterization laboratory. The patients were ventilated for 5.1 +/- 3.3 hours. Blood transfusion was given to 8 patients. Apart from 2 groin bleedings, no other complications occurred. Patients left our hospital after 3.2 +/- 2.8 days. Of the 4 patients who died during the 15 +/- 12 month follow-up, 1 died of a noncardiac cause. In conclusion, in highly selected patients ineligible for bypass surgery, ELS-supported PCI can be performed with promising short- and long-term clinical outcomes. This complex procedure is a safe alternative whenever other options for revascularization are exhausted. PMID- 17350361 TI - A cost-minimization analysis of the angio-seal vascular closure device following percutaneous coronary intervention. AB - The Angio-Seal vascular closure device has been shown to be safe and effective in decreasing the time to hemostasis after percutaneous coronary intervention (PCI). The health economic implications of routinely using Angio-Seal after PCI have not been explored. We performed a cost-minimization analysis comparing routine Angio Seal use after PCI with mechanical compression using a decision analytic model. The relative probabilities of 7 vascular access complications were derived from pooled analysis of published randomized trials. The incremental hospital cost of each vascular complication was estimated by a matched case-control analysis of 3,943 patients who underwent PCI at our center from January 2002 and December 2004. Appropriate sensitivity and uncertainty analyses were performed. After accounting for differences in expected rates of specific complications between the 2 strategies and the incremental costs of each vascular event, the routine use of Angio-Seal was associated with a lower cost per PCI procedure of 44 dollars. Probabilistic sensitivity analysis of all model assumptions using second order Monte Carlo simulation confirmed the economic advantage of Angio-Seal in 74% of model replications. In conclusion, after PCI, the routine use of Angio Seal for femoral vascular access management was associated with net cost savings compared with mechanical compression. This cost savings was in addition to the previously demonstrated advantages of Angio-Seal in terms of patient comfort and preference. PMID- 17350363 TI - Frequency of coronary arterial late angiographic stent thrombosis (LAST) in the first six months: outcomes with drug-eluting stents versus bare metal stents. AB - Concerns have been raised about the long-term safety of drug-eluting stent (DES) implantation due to late angiographic stent thrombosis (LAST). We investigated the incidence and 6-month clinical and angiographic outcomes of LAST after DES versus bare metal stent (BMS) implantation. This study comprised 6,551 patients treated with BMSs (n = 4,104) or DESs (n = 2,447). LAST was defined as angiographically proved stent thrombotic occlusion with acute ischemic symptoms >30 days after stenting. Major adverse cardiac events were defined as death, Q wave myocardial infarction, and target lesion revascularization. Patients treated with DESs had a significantly higher risk profile than did patients treated with BMSs. There were 8 cases (0.33%) of LAST in the DES group and 7 (0.17%) in the BMS group, showing similar event rates after risk adjustment (adjusted hazard ratio 1.2, 95% confidence interval 0.1 to 18.4, p = 0.9). Four patients with LAST treated with DESs (50%) and 1 treated with BMSs (14%) were associated with discontinuation of antiplatelet therapy. Two cases (25%) of LAST with DESs occurred in patients on aspirin monotherapy and another 2 cases (25%) occurred in patients on dual antiplatelet therapy. There was no case of in-hospital death associated with LAST events. At 6-month follow-up after LAST events, major adverse cardiac events occurred in only 3 patients (43%) in the BMS group. In conclusion, the incidence of LAST was similar after DES and BMS implantations. LAST treated with DESs was associated with antiplatelet therapy discontinuation in a significant number of patients, and LAST events also developed on dual antiplatelet therapy. Patients with LAST and DESs showed favorable outcomes during follow-up. PMID- 17350364 TI - Comparison of coronary drug-eluting stents versus coronary artery bypass grafting in patients with diabetes mellitus. AB - We compared 1-year outcome after drug-eluting stent (DES) implantation with off pump bypass grafing (OPCABG) in patients with type 2 diabetes mellitus and multivessel coronary artery disease involving the proximal segment of the left anterior descending coronary artery. All consecutive diabetic patients treated by DES (DES group) or OPCABG (CABG group) in our institution from April 2002 to December 2004 because of de novo coronary lesions were included. Patients in the CABG group (n = 149) were older and had a higher rate of 3-vessel disease than those in the DES group (n = 69). At 12 months, major adverse cardiac and cerebrovascular events occurred in 29% of the DES group and 20.5% of the CABG group (unadjusted analysis, odds ratio 1.20, 95% confidence interval [CI] 0.93 to 1.54, p = 0.17). After propensity score analysis, adjusting for baseline differences between the 2 cohorts, DESs increased the risk of 12-month major adverse cardiac and cerebrovascular events (hazard ratio 1.88, 95% CI 1.09 to 3.02, p = 0.020). This was due to the higher rate for repeat revascularization in the DES group (19% vs 5%, odds ratio 2.05, 95% CI 1.12 to 3.75, p = 0.001). In contrast, there was no difference in the rate of the composite end points of death, myocardial infarction, and stroke (DES group 13%, CABG group 12%; adjusted analysis, hazard ratio 0.80, 95% CI 0.80 to 1.35, p = 0.40). In conclusion, at 1 year in diabetic patients with multivessel coronary artery disease involving the proximal left anterior descending coronary artery, the advantage of OPCABG over DES implantation seems to be limited at a lower rate of repeat revascularization. No difference seems to exist in the rate of death, stroke, and myocardial infarction. PMID- 17350365 TI - Influence of preoperative lipid-lowering therapy on postoperative outcome in patients undergoing coronary artery bypass grafting. AB - Statin therapy has recently been shown to decrease adverse perioperative events in patients undergoing vascular surgery. The potential beneficial effect of lipid lowering therapy in patients undergoing coronary artery bypass grafting (CABG) is not well known. This was an observational analysis of 4,739 patients who underwent first-time isolated CABG at a single institution from 1995 to 2001. Patients were categorized into 2 groups based on treatment with a lipid-lowering agent within 30 days before surgery. Univariate and multivariate analyses were used to determine the association between lipid-lowering therapy and survival to hospital discharge. Patients in the lipid-lowering group (n = 2,334) tended to be younger (mean age 66 +/- 10 vs 68 +/- 10 years), were more likely to be diabetic (31% vs 28%), and on beta blockers (77% vs 70%) than patients in the nonlipid lowering group (n = 2,405). In-hospital mortality was significantly lower in the lipid-lowering group than in the nonlipid-lowering therapy group (1.4% vs 2.2%, odds ratio 0.62, 95% confidence interval 0.40 to 0.96, p = 0.03). A multivariable model demonstrated a loss of statistical significance for the effect of lipid lowering therapy on in-hospital mortality (adjusted odds ratio 0.83, 95% confidence interval 0.5 to 1.37, p = 0.46). In conclusion, preoperative use of lipid-lowering therapy in patients undergoing CABG appears safe and is associated with improved survival to hospital discharge compared with patients not receiving lipid-lowering therapy. However, patient risk factors and other cardioprotective medication use associated with the use of preoperative lipid-lowering therapy appear to explain the association with improved survival. PMID- 17350366 TI - Relation of plaque size to necrotic core in the three major coronary arteries in patients with acute coronary syndrome as determined by intravascular ultrasonic imaging radiofrequency. AB - According to pathologic studies, the content of a necrotic core increases in a "linear fashion" as plaque enlarges. In addition, these 2 plaque characteristics have been associated with plaque vulnerability. This study assessed the relation between plaque cross-sectional area (CSA) and content of necrotic core (NC). Twenty-five patients (75 arteries) with acute coronary syndrome were studied. In total, 7,834 CSAs were analyzed. An analysis of plaque CSA in percentiles was performed (median 5.5 mm(2), interquartile range 3.7 to 7.8); subsequently, plaque CSA values were categorized as small (< or = 3.7 mm(2)), medium (>3.7 to < or = 7.8 mm(2)), and large (>7.8 mm(2)). There was a difference in content of the NC between arteries within each plaque CSA category. This observation was confirmed in a multivariate analysis in which only 2 variables remained statistically significant, plaque CSA (estimate 1.34, SE 0.05, p <0.0001) and studied artery (left anterior descending coronary artery, estimate 0.29, SE 0.08, p = 0.0003; left circumflex coronary artery, estimate 0.23, SE 0.07, p = 0.0014; and these vs the right coronary artery). In conclusion, the NC and plaque increase in patients with acute coronary syndromes. PMID- 17350367 TI - Impact of initial heart rate and systolic blood pressure on relation of age and mortality among fibrinolytic-treated patients with acute ST-elevation myocardial infarction presenting with cardiogenic shock. AB - Older age is associated with worse outcomes in patients with cardiogenic shock complicating ST-elevation myocardial infarction (STEMI). However, significant heterogeneity exists in different age groups with respect to outcomes. Identification of factors that modulate age-related risk of death in patients with cardiogenic shock may help clinical decision making and facilitate patient counseling. Accordingly, we evaluated 761 patients with STEMI who presented with cardiogenic shock and received fibrinolysis. We categorized patients into 3 age groups (<60 years, n = 224; 60 to 75 years, n = 360; and > or = 75 years, n = 177). Death at 30 days occurred in 118 patients <60 years of age (53%), 214 patients 60 to 75 years of age (59%), and 127 patients > or = 75 years of age (72%) with cardiogenic shock. Factors associated with death (per 10-U change) on multivariable analysis were older age (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.23 to 1.66), higher heart rate (OR 1.27, 95% CI 1.19 to 1.35), and lower systolic blood pressure (OR 1.32, 95% CI 1.23 to 1.41, c index 0.79). Important interactions were found with age, heart rate, and systolic blood pressure, suggesting that, although age was a strong independent predictor of death in patients with a heart rate < or = 100 beats/min, it was less strongly related to death in patients with a heart rate >100 beats/min in whom prognosis was uniformly poor. Further, elderly patients with a systolic blood pressure >80 mm Hg had substantial chance of recovery. In contrast, those with a systolic blood pressure < or = 80 mm Hg and heart rate >100 beats/min had 30-day death rates >90% even if they were young. In conclusion, our data suggest that, although elderly patients with cardiogenic shock have poor prognosis, presenting heart rate and systolic blood pressure provide important information to differentiate who may have greater chance of recovery. This information may help physicians in deciding treatment options for patients with cardiogenic shock and counseling them about their risks. PMID- 17350368 TI - A practical approach with outcome for the prognostic assessment of non-ST-segment elevation chest pain and normal troponin. AB - Patients with non-ST-elevation chest pain constitute a heterogeneous population. Our aim is to compare the outcome of patients with chest pain, non-ST-segment deviation, and normal troponin, categorized using a risk score, with that of patients with ST depression or troponin increase. A total of 1,449 patients with non-ST-elevation chest pain were evaluated. A validated risk score (using pain characteristics and risk factors) was applied to patients without ST depression or troponin increase. Accordingly, 4 risk categories were defined: group 1, no troponin increase, no ST depression, and risk score <3 points (n = 633); group 2, no troponin increase, no ST depression, but risk score > or = 3 points (n = 158); group 3, no troponin increase, ST depression (n = 106); and group 4, troponin increase (n = 552). Median follow-up was 26 months, and the end point was death or myocardial infarction. Group 1 experienced fewer events at 30 days (1.7%, p = 0.0001) and long-term follow-up (9.4%, p = 0.0001) than groups 2 (10.8% and 26%), 3 (6.6% and 30%), and 4 (9.5% and 25%). Kaplan-Meier curves overlapped among groups 2, 3, and 4, whereas group 1 showed a flatter curve (p = 0.0001). Using multivariate analysis, risk group (group 1 vs remaining groups) predicted 30-day (p = 0.0003) and long-term (p = 0.0001) outcome. There were no differences among groups 2, 3, and 4. In conclusion, application of a risk score to patients without troponin increase or ST deviation identified a high-risk group with prognosis similar to that of patients with troponin increase or ST depression and affords a practical classification for the full spectrum of non-ST-elevation chest pain. PMID- 17350369 TI - Microbiological profile of septic complication in patients with cardiogenic shock following acute myocardial infarction (from the SHOCK study). AB - We sought to assess the microbiologic profile of patients with suspected sepsis who participated in the SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK? (SHOCK) trial, a randomized controlled trial of early coronary revascularization in patients with cardiogenic shock complicating acute myocardial infarction. A protocol-mandated SEPSIS form was completed prospectively for 54 patients (18%) with fever or leukocytosis suggestive of sepsis. These patients were divided further into those with positive (n = 40) or negative (n = 14) culture results. The predominant pathogen isolated in patients with positive culture results was Staphylococcus aureus (32%), followed by Klebsiella pneumoniae and Pseudomonas aeruginosa. Patients with both positive and negative culture results had longer median durations of mechanical ventilation (p <0.001 and p = 0.02), intra-aortic balloon pump (IABP) support (p = 0.074 and p = 0.021), and hospital stay (p <0.001 and p = 0.048) than controls. Sepsis was predicted by both duration of IABP support (p = 0.007) and use of multiple central catheters (p = 0.026). In conclusion, clinical sepsis is common after cardiogenic shock complicating acute myocardial infarction, particularly in patients who received prolonged IABP support or had multiple central catheters. PMID- 17350370 TI - Effect of colchicine (0.5 mg twice daily) on high-sensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease. AB - In patients with stable coronary artery disease, elevated levels of biomarkers of inflammation, including high-sensitivity C-reactive protein (hs-CRP) > or = 2.0 mg/L, are predictors of future vascular events. Because long-term low-dose colchicine is a safe and effective means of dampening inflammation, we conducted an open-label pilot study to determine whether it could significantly lower hs CRP in patients with stable coronary artery disease in whom hs-CRP was > or = 2.0 mg/L despite taking both aspirin and high-dose atorvastatin therapy. Plasma hs CRP was measured in 200 patients with clinically stable coronary artery disease who were taking aspirin and atorvastatin. In 64 patients, hs-CRP was > or = 2.0 mg/L. In 20 of these patients, hs-CRP was measured again at 2 weeks (no treatment group), and in 44 patients, hs-CRP was measured again after 4 weeks of open-label colchicine 0.5 mg twice daily (treatment group). In the no treatment group, mean baseline hs-CRP did not decrease significantly, measuring 4.28 +/- 2.03 mg/L at baseline and 3.70 +/- 2.30 mg/L after repeated measurement (mean change 11.0%, 95% confidence interval [CI] -30% to +9%, p = NS). In contrast, hs-CRP decreased in all patients administered colchicine, with mean baseline hs-CRP decreasing from 4.58 +/- 2.05 to 1.78 +/- 1.38 mg/L (p <0.001), an absolute decrease of 2.80 mg/L (95% CI 2.40 to 3.65 mg/L) and a relative decrease of 60% (95% CI 54% to 67%). In 28 patients (64%) in this group, the decrease in hs-CRP was >50% from baseline, and in 31 patients (70%), hs-CRP decreased to <2.0 mg/L. No significant side effects were reported. In conclusion, low-dose colchicine (0.5 mg twice daily) can effectively decrease hs-CRP in patients with clinically stable coronary artery disease and increased hs-CRP independent of aspirin and atorvastatin use. Additional controlled studies are warranted to confirm this observation and determine whether long-term use of low-dose colchicine can improve clinical outcomes in patients with advanced vascular disease. PMID- 17350371 TI - Glutathione peroxidase-1 activity, atherosclerotic burden, and cardiovascular prognosis. AB - Recent findings suggest that erythrocyte intracellular glutathione peroxidase-1 (GPX-1) activity is related inversely to future cardiovascular events. The aim of this study is to evaluate the association of GPX-1 activity to extent of atherosclerosis, as well as its long-term prognosis in context with atherosclerotic burden. In a prospective study, we included 508 patients before coronary angiography. Atherosclerosis of carotid and leg arteries was documented using sonographic methods. Blood samples were drawn after an overnight fasting period, and GPX-1 activity was determined in washed erythrocytes. GPX-1 activity tended to decrease with increasing numbers of atherosclerotic vascular beds, so that patients without clinically relevant atherosclerosis had GPX-1 activity of 49.3 U/g hemoglobin compared with 46.0 U/g hemoglobin in patients with prevalent atherosclerosis in all 3 vascular beds (p = NS). Follow-up data (median 6.5 years) were available for 504 patients (99.2%), and 96 patients (19.0%) experienced cardiovascular events (cardiovascular death, infarction, and stroke). The event rate was inversely associated with level of GPX-1 activity divided into tertiles (hazard ratio 2.3, 95% confidence interval 1.4 to 4.0 for lowest vs highest tertile of GPX-1 activity, p = 0.002, adjusted). The highest event rate was found in persons with low GPX-1 activity and multivascular atherosclerosis (event rate 36.9%, p <0.0001). In conclusion, decreased red blood cell GPX-1 activity is associated with increased cardiovascular risk according to the extent of atherosclerosis. PMID- 17350372 TI - Comparison of coronary atherosclerotic volume in patients with glomerular filtration rates < or = 60 versus > 60 ml/min/1.73 m(2): a meta-analysis of intravascular ultrasound studies. AB - The relation between glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) and the extent and progression of coronary atherosclerosis in 989 subjects with coronary artery disease was investigated. Despite being older, more likely to be women, and having a history of hypertension, diabetes, and bypass surgery, total atheroma volume and percent atheroma volume in subjects with a low GFR did not differ from subjects with a GFR >60 ml/kg/min. Similarly, there was no difference in progression rates of total atheroma volume and percent atheroma volume in patients with GFRs lower and higher than 60 ml/min/1.73 m(2) in response to a high rate of use of established preventive therapies. In conclusion, findings suggest that the increased incidence of clinical events in patients with impaired renal function may result from factors other than atherosclerotic burden. PMID- 17350373 TI - Electrocardiographic differentiation between acute pulmonary embolism and acute coronary syndromes on the basis of negative T waves. AB - Negative T waves in precordial leads are often seen in patients with acute coronary syndrome (ACS), but also occur in those with acute pulmonary embolism (APE). However, little attention has been given to differences in negative T waves between patients with these 2 diseases. The present study examines the value of electrocardiograms for discriminating between 40 patients with APE and 87 patients with ACS who had negative T waves in the precordial leads (V(1) to V(4)) on the admission electrocardiogram. In 77 patients (89%) with ACS, the culprit lesion was confirmed angiographically to be located in the left anterior descending coronary artery. Pulmonary P waves, S(1)S(2)S(3) pattern, S(1)Q(3)T(3) pattern, low voltage, and clockwise rotation were specific for APE, but sensitivities of these findings were very low. In patients with APE, negative T waves were commonly present in leads II, III, aVF, V(1), and V(2), but were less frequent in leads I, aVL, and V(3) to V(6) (p <0.05). Negative T waves in leads III and V(1) were observed in only 1% of patients with ACS compared with 88% of patients with APE (p <0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of this finding for the diagnosis of APE were 88%, 99%, 97%, and 95%, respectively. In conclusion, the presence of negative T waves in both leads III and V(1) allows APE to be differentiated simply but accurately from ACS in patients with negative T waves in the precordial leads. PMID- 17350374 TI - Cardiac arrest in patients who smoke crack cocaine. AB - The aim of the study is to determine the clinical features and outcomes of cocaine users admitted to the hospital after cardiac arrest and compare them with nonusers. Cocaine is associated with cardiovascular complications, including ventricular arrhythmias; however, resuscitated cardiac arrest in relation to cocaine use is not a well-defined clinical entity. We reviewed available hospital charts at San Francisco General Hospital with the International Classification of Diseases, Ninth Revision diagnosis of cardiac arrest and cocaine use from 1994 to 2006. Clinical features and outcomes of cocaine users were compared with those of randomly selected control patients and age-matched controls with resuscitated cardiac arrest without cocaine use. We identified 22 patients with resuscitated cardiac arrest in the setting of cocaine use. Their average age was 42 +/- 10 years, >20 years younger than nonusers (68 +/- 16 years, p <0.01). After cardiac arrest, 12 of 22 patients (55%) who used cocaine had complete neurologic recovery in contrast to only 3 of 20 unmatched controls (15%, p <0.01) and 7 of 41 age matched controls (17%, p <0.01). Only 10 of 22 cocaine users (46%) died compared with 15 of 20 unmatched controls (75%, p = 0.05) and 32 of 41 age-matched controls (78%, p <0.01). In a combined analysis of all patients, cocaine use was the only significant predictor of neurologic recovery (p <0.01) and survival (p <0.01). In conclusion, cocaine use is associated with cardiac arrest. In patients with cardiac arrest, cocaine users are younger than nonusers and more likely to survive with neurologic recovery, even compared with age-matched controls with cardiac arrest. PMID- 17350375 TI - Relation of family history of myocardial infarction and the presence of coronary arterial calcium in various age and risk factor groups. AB - Family history of myocardial infarction (FHMI) is an independent risk factor for cardiovascular (CV) events but may be more informative in certain subgroups. The association between FHMI and the presence of coronary artery calcium (CAC) was examined in various age and risk factor groups in the Dallas Heart Study (DHS), a population-based probability sample of subjects aged 30 to 65 years. Analyses were stratified by age (with the young group composed of men aged <45 years and women aged <55 years) and by the presence of 0, 1, 2, or >2 CV risk factors. In the overall cohort of 2,743 subjects, FHMI was an independent predictor of CAC (adjusted odds ratio 1.3, 95% confidence interval 1.1 to 1.7), attributable to an independent association between FHMI and CAC in the young group (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1) that was not evident in the older subset (adjusted odds ratio 1.2, 95% confidence interval 0.91 to 1.6, interaction p = 0.02). In the young cohort, the association between FHMI and CAC was particularly robust in those with > or = 2 risk factors (FHMI-by-risk factor interaction p = 0.04). In older subjects, FHMI was not associated with CAC for any risk factor category (p >0.05 for each). In conclusion, this study suggests that FHMI is a more important predictor of atherosclerosis in young compared with older adults and, among the young, in those with multiple CV risk factors. PMID- 17350376 TI - Prevalence and clinical correlates of isolated mitral, isolated aortic regurgitation, and both in adults aged 21 to 35 years (from the CARDIA study). AB - Aortic regurgitation (AR) and mitral regurgitation (MR) can result in serious clinical complications and death. The physiologic and clinical correlates of AR and MR in a free-living young adult population, however, have not been well defined. The prevalence and correlates of AR and MR were investigated in Coronary Artery Risk Development in Young Adults (CARDIA), a multicenter National Heart, Lung, and Blood Institute study of 4,352 men and women aged 21 to 35 years who had 2-dimensionally directed M-mode echocardiographic and spectral and color Doppler examinations. Isolated MR by color Doppler was detected in 10.4% (90.4% with trivial or mild severity). Isolated AR by color Doppler was present in 0.8% (37.7% with mild severity). Combined AR and MR occurred in 0.5%. There was no association between body mass index and the prevalence or severity of MR or AR. Left ventricular mass was greater in subjects with isolated AR (mean +/- SD 172 +/- 49 g) than in those with MR (155 +/- 48 g) and greater in both groups than in subjects without MR and AR (148 +/- 44 g). AR was associated with increased aortic root diameter, whereas subjects with isolated MR and those with AR and MR had increased left atrial dimensions and greater left ventricular internal dimensions. In conclusion, MR and AR detected by color Doppler echocardiography are relatively uncommon in a healthy young adult population, but both are associated with evidence of increased left ventricular dimensions and mass. PMID- 17350377 TI - Prognostic significance of exercise induced arrhythmias and echocardiographic variables in hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HC) often presents with exercise-induced symptoms, including arrhythmias and sudden death. The investigators prospectively studied whether exercise testing is associated with immediate complications and if stress induced arrhythmias and echocardiographic variables are associated with long-term adverse outcomes. Exercise echocardiography with 6-channel continuous monitoring for arrhythmias was performed in consecutive patients with HC clinically referred for the test. End points included death, myocardial infarction, revascularization, stroke, atrial fibrillation, ventricular tachycardia, and myectomy. Of 86 patients with HC (mean age 56.6 +/- 16.1 years) who underwent exercise echocardiography, arrhythmias occurred in 39 (45%), including 23 (27%) with premature atrial contractions, 2 (2%) with atrial fibrillation, 28 (33%) with premature ventricular contractions (16 also had atrial arrhythmias), and 1 (1.2%) with nonsustained ventricular tachycardia (hemodynamically stable). During a follow-up of 2.6 +/- 2.8 years, major events occurred in 11 patients (3 deaths, 5 revascularizations, 3 strokes). In addition, 12 patients developed atrial fibrillation, 6 developed nonsustained ventricular tachycardia, and 13 underwent myectomies. Variables associated with major events included hypertension, male gender, and worsening wall motion score index with exercise; increased exercise duration was associated with fewer events. ST-T changes on baseline electrocardiography and premature ventricular contractions were associated with atrial fibrillation risk. In conclusion, in this cohort of patients with HC, exercise testing was safe. Test results were associated with risk for adverse events. PMID- 17350378 TI - Health care resource utilization in adults with congenital heart disease. AB - The number of adults with congenital heart disease (CHD) is increasing. However, rates of health care resource utilization in this population are unknown. The objectives of this study were to describe the use of general health care resources in adults with CHD and to examine the impact of CHD severity on resource utilization. The study consisted of adults alive in 1996 who had > or = 1 diagnosis of a CHD lesion conforming to the International Classification of Disease, Ninth Revision, in the physician's claims database of the province of Quebec from 1983 to 2000. From 1996 to 2000, rates of health care utilization were measured. The impact of the severity of CHD on the use of health care resources was determined using multivariate models to adjust for age, gender, Charlson co-morbidity score, and duration of follow-up. The study population consisted of 22,096 adults with CHD (42% men). From 1996 to 2000, 87% received outpatient care from specialists, 68% visited emergency rooms, 51% were hospitalized, and 16% were admitted to critical care units. Patients with severe CHD had higher adjusted rates of outpatient cardiologist care (rate ratio [RR] 2.24, 95% confidence interval [CI] 2.06 to 2.45), emergency department utilization (RR 1.09, 95% CI 1.03 to 1.17), hospitalization (RR 1.30, 95% CI 1.19 to 1.43), and days in critical care (RR 2.12, 95% CI 1.80 to 2.50) than patients with other congenital cardiac lesions. Hospitalization rates were higher than in the general Quebec adult population (RR 2.08, 95% CI 2.00 to 2.17). In conclusion, adults with CHD have high rates of health care resource utilization, particularly those with severe lesions. Appropriate resource allocation is required to serve this growing population. PMID- 17350379 TI - Association of arterial wave properties and diastolic dysfunction in patients with type 2 diabetes mellitus. AB - Left ventricular (LV) diastolic dysfunction and increased arterial stiffness are prevalent in patients with type 2 diabetes mellitus (DM). Because the systemic vasculature plays a pivotal role in myocardial loading, this study aimed to determine the effect of arterial characteristics on LV diastolic function in patients with type 2 DM. Conventional echocardiography and tissue Doppler imaging were performed in 155 patients with type 2 DM (88 men; mean age 55 +/- 11 years) with preserved LV ejection fractions (>50%). Patients were stratified into groups on the basis of LV diastolic function (normal, n = 53; delayed relaxation, n = 79; pseudonormal, n = 23). Arterial wave reflection parameters and central blood pressure were determined by radial tonometry. Arterial (brachial and carotid) structure and function were determined by standard ultrasound methods. There were no significant differences among the groups on central pressure or arterial function. LV filling pressure, determined by the ratio of early transmitral inflow velocity to diastolic early tissue velocity (E/E'), was significantly correlated with central pulse pressure (r = 0.21, p <0.05). Late diastolic inflow velocity (A) was significantly associated with central pulse pressure (r = 0.32, p <0.001), total arterial compliance (r = -0.35, p <0.001), and carotid artery stiffness (r = 0.34, p <0.001). Multiple regression analysis found central but not brachial pulse pressure independently predicted E/E' and A. In conclusion, increased central pulse pressure, possibly due to amplified pressure wave reflections, is independently associated with abnormal LV diastolic function in patients with type 2 DM. PMID- 17350380 TI - Major adverse cardiac events during endurance sports. AB - Major adverse cardiac events in endurance exercise are usually due to underlying and unsuspected heart disease. The investigators present an analysis of major adverse cardiac events that occurred during 2 consecutive annual long distance races (a 36-km beach cycling race and a 21-km half marathon) over the past 5 years. All patients with events were transported to the hospital. Most of the 62,862 participants were men (77%; mean age 40 years). Of these, 4 men (3 runners, 1 cyclist; mean age 48 years) collapsed during (n = 2) or shortly after the races, rendering a prevalence of 0.006%. Two patients collapsed after developing chest pain, 1 of whom needed resuscitation at the event site, which was successful. These patients had acute myocardial infarctions and underwent primary angioplasty. The third patient was resuscitated at the site but did not have coronary disease or inducible ventricular tachycardia or ventricular fibrillation and collapsed presumably because of catecholamine-induced ventricular fibrillation. The fourth patient experienced heat stroke and had elevated creatine kinase-MB and troponins in the absence of electrocardiographic changes. In conclusion, the risk for major adverse cardiac events during endurance sports in well-trained athletes is very low. PMID- 17350381 TI - Frequency of and inappropriate treatment of misdiagnosis of acute aortic dissection. AB - Acute aortic syndrome (AAS) comprises acute aortic dissection, intramural hematoma, and penetrating ulcer of the aorta. The importance of accurate, rapid diagnosis and intervention for AAS is underscored by its clinical and epidemiologic overlap with acute coronary syndrome and by the risks of inappropriate treatment with antithrombotic agents. To explore these concerns, the recognition, management, and outcomes of AAS in the contemporary experience of a tertiary referral center were reviewed. Sixty-six consecutive patients with AAS admitted from January 2000 to December 2004 were identified, and their records reviewed. Misdiagnosis occurred in 39% (n = 26) and was associated with longer time to correct diagnosis (mean +/- SEM 51 +/- 12 vs 15 +/- 5 hours, p = 0.003). Acute coronary syndrome was the most common misdiagnosis, resulting in inappropriate treatment with acetylsalicylic acid in 26 (100%), clopidogrel in 1 (4%), heparin in 22 (85%), and fibrinolytic agents in 3 (12%). Exposure to antithrombotic agents was associated with higher rates of major bleeding (38% vs 13%) and a trend toward greater in-hospital mortality (27% vs 13%) (p = 0.02 for combined end point). Antithrombotic agent administration was also associated with increased hemorrhagic pericardial fluid (50% vs 25%), hemorrhagic pleural effusion (15% vs 3%), and hemodynamic instability (30% vs 13%) (p = 0.02 for combined end point). In conclusion, AAS is frequently confused with acute coronary syndrome, leading to delayed diagnosis and clinically significant bleeding as a consequence of inappropriate treatment with antithrombotic agents. PMID- 17350382 TI - Evaluation of chest barriers for protection against sudden death due to commotio cordis. AB - Blunt precordial blows triggering ventricular fibrillation (commotio cordis) represent a leading cause of sudden death in young athletes. Attention has focused on the primary prevention of these tragedies with chest barriers. The U.S. Commotio Cordis Registry was accessed to determine the likelihood of sudden death in athletes exposed to precordial blows while wearing chest protectors. Of 182 cases of commotio cordis, 85 (47%) occurred during practice or competition in organized sports. In 32 of these 85 competitive athletes (38%), fatal chest blows occurred despite the presence of potentially protective equipment. Athletes wore standard, commercially available chest barriers made of polymer foam covered by fabric or hard shells, generally perceived as protective from arrhythmic consequences of the blows. These events occurred in 4 sports: hockey (n = 13; 1 goalie), football (n = 10), lacrosse (n = 6; 3 goalies), and baseball (n = 3; all catchers). Scenarios included the failure of the padding to cover the precordium so that blows circumvented the protective barrier (n = 25) or projectiles that struck the chest barrier directly (n = 7). In conclusion, a significant proportion (about 40%) of sudden deaths reported in young competitive athletes due to blunt chest blows (commotio cordis) occur despite the presence of commercially available sports equipment generally perceived as protective. PMID- 17350383 TI - Effect of anger provocation on endothelium-dependent and -independent vasodilation. AB - Anger is an independent predictor of coronary heart disease events, although the mechanisms for this relation are unclear. The effects of an anger-provoking interview compared with a neutral interview on endothelium-dependent and independent vasodilation assessed by brachial artery ultrasound were examined in 14 healthy subjects without coronary heart disease risk factors. The anger provocation condition, but not the neutral condition, caused a significant impairment in endothelium-dependent vasodilation at 90 minutes compared with baseline (p = 0.004) and 30 minutes (p = 0.013). Similarly, endothelium independent vasodilation was significantly impaired at 90 minutes after the angry interview compared with baseline (p = 0.003) and 30 minutes (p = 0.001). The decreases in endothelium-dependent and -independent vasodilation were greater after the anger-provoking interview than after the neutral interview, especially between 30 and 90 minutes. In conclusion, preliminary results suggest that an episode of anger is associated with a dysregulation in endothelium-dependent and independent pathways, suggesting that these mechanisms might contribute to the link between anger and coronary heart disease events. PMID- 17350384 TI - Comparison of three-dimensional echocardiography to two-dimensional echocardiography and fluoroscopy for monitoring of endomyocardial biopsy. AB - Real-time 3-dimensional echocardiography (RT3DE) offers the rapid acquisition of quantitative and qualitative anatomic data without the use of geometric assumptions. This study was designed to test the feasibility and potential superiority of RT3DE versus 2-dimensional echocardiography (2DE) and standard fluoroscopy for monitoring endomyocardial biopsies (EMBs). Thirty-eight consecutive EMBs performed under fluoroscopic guidance in 26 patients were monitored using 2DE and RT3DE alternately. Two reviewers scored each biopsy pass for visualization of the tip of the bioptome and location of the actual biopsy. Overall image quality was noted as good or poor, and the effect of image quality on tip localization was analyzed. A total of 243 biopsy attempts were made during 38 EMBs. The location of the biopsy was determined in 74% of the biopsies monitored with RT3DE, whereas 2DE demonstrated the location with certainty in only 43% of the biopsies (p <0.0001). On a procedure-by-procedure comparison, RT3DE was found to show the bioptome tip better in 23 of 38 biopsies, compared with 1 of 38 for 2DE (p = 0.001). In 14 of 38 EMBs, neither method was clearly better. In conclusion, RT3DE improves the ability to see the location of the bioptome during EMB compared with 2DE and fluoroscopy. PMID- 17350385 TI - Mechanism of troponin elevations in patients with acute ischemic stroke. AB - Ischemic heart disease and cerebrovascular diseases frequently co-exist in the same patient, and similar risk factors are shared. For 60 years, experimental, observational, and clinical trial data have incessantly indicated that neurologically induced myocardial injury exists. Since the introduction of troponin in the diagnosis of acute myocardial infarction, this marker has been measured in a number of other conditions as well. One of these conditions is acute ischemic stroke, causing diagnostic dilemmas for clinicians. Because various electrocardiographic alterations have also been reported in these patients, it has been suggested that elevated troponin levels are somehow neurologically mediated, thus not caused by direct cardiac release. In conclusion, this review examines the available studies that systematically measured troponin in patients with acute ischemic stroke to properly interpret troponin elevations in these patients. PMID- 17350386 TI - Usefulness of computed tomographic angiography guided percutaneous coronary intervention. AB - The intravascular ultrasound qualities of coronary computed tomographic angiography provide the rationale for a new approach to the selection of patients for percutaneous coronary intervention and to guide the performance of the procedure. Minimum luminal diameter and minimum luminal area derived from computed tomographic angiography are readily measured and are used to triage patients to medical therapy or angiographic evaluation, with subsequent decisions based on the severity of disease and intravascular ultrasound findings. Technical decisions related to percutaneous coronary intervention are guided by lesion length and plaque characteristics. In conclusion, computed tomographic angiography has the requisite intravascular ultrasound characteristics to greatly impact percutaneous coronary intervention. PMID- 17350387 TI - Obesity and mortality: a poorly understood relationship. PMID- 17350388 TI - Atherosclerosis assessment confounders in the Rancho Bernardo study. PMID- 17350389 TI - Left atrium in hypertrophic cardiomyopathy: time for reconsideration of its clinical importance? PMID- 17350390 TI - CAMELOT tales: trials and tribulations of Sir Lancelot and Lady Guinevere. PMID- 17350395 TI - Intensive care unit robotic telepresence facilitates rapid physician response to unstable patients and decreased cost in neurointensive care. AB - BACKGROUND: The timely assessment and treatment of ICU patients is important for neurosurgeons and neurointensivists. We hypothesized that the use of RTP can improve physician rapid response to unstable ICU patients. METHODS: This is a prospective study using a before-after, cohort-control design to test the effectiveness of RTP. Physicians used RTP to make rounds in the ICU in response to nursing pages. Data concerning several aspects of the RTP interaction including the latency of the response, the problem being treated, the intervention that was ordered, and the type of information gathered using the RTP were documented. The effect of RTP on ICU length of stay and cost was assessed. RESULTS: The use of RTP was associated with a reduction in latency of attending physician face-to-face response for routine and urgent pages compared to conventional care (RTP: 9.2 +/- 9.3 minutes vs conventional: 218 +/- 186 minutes). The response latencies to brain ischemia (7.8 +/- 2.8 vs 152 +/- 85 minutes) and elevated ICP (11 +/- 14 vs 108 +/- 55 minutes) were reduced (P < .001), as was the LOS for patients with SAH (2 days) and brain trauma (1 day). There was an increase in ICU occupancy by 11% compared with the prerobot era, and there was an ICU cost savings of $1.1 million attributable to the use of RTP. CONCLUSION: The use of RTP enabled rapid face-to-face attending physician response to ICU patients and resulted in decreased ICU cost and LOS. PMID- 17350396 TI - Multimedia Messaging Service teleradiology in the provision of emergency neurosurgery services. AB - BACKGROUND: Neurosurgical emergencies constitute a significant proportion of workload of a tertiary neurosurgical service. Prompt diagnosis and emergent institution of definitive treatment are critical to reduce neurological mortality and morbidity. Diagnosis is highly dependent on accurate interpretation of scans by experienced clinicians. This expertise may not be readily available especially after office hours because many neurosurgical units are manned by middle-level neurosurgical staff with varying levels of experience in scan interpretation. Multimedia Messaging Service mobile phone technology offers a simple, cheap, quick, and effective solution to the problem of scan interpretation. An MMS takes only a few minutes to send and receive and allows senior doctors to view important images and make important clinical decisions to enhance patient management in an emergency situation. METHODS: A mobile phone (with VGA camera and MMS capabilities) was provided to the neurosurgery registrar on call. The on call mobile phone is passed on to the corresponding registrar on-call the next day. All consultants had personal mobile phones that are MMS-enabled. Relevant representative CT/MRI images can be taken directly from the mobile phone from the PACS off the computer screen. When only hard copies are available, the images can be taken off the light box. After a 12-month trial period, a questionnaire was given to all staff involved in the project to ascertain the usefulness of the MMS teleradiology service. RESULTS: The survey on the use of the MMS service in a tertiary neurosurgical service demonstrated that the technology significantly improved the level of confidence of the senior-level staff in emergent clinical decision making. Significantly, the MMS images were of sufficient quality and resolution to obviate the need to view the actual scans. The impact of MMS is less pronounced in the middle-level staff, but there was a trend that most of the junior staff found the service more useful. CONCLUSION: The MMS technology is demonstrated to be a useful media for the transmission of high-quality images to assist in the diagnostic process and implementation of emergent clinical therapy. It is already in widespread use and can be seamlessly and rapidly implemented in the clinical arena to improve the quality of patient care. PMID- 17350397 TI - Endoscopic endonasal transsphenoidal surgery. Before scrubbing in: tips and tricks. AB - BACKGROUND: The interest in endoscopic endonasal transsphenoidal surgery for the treatment of sellar and perisellar lesions is growing as a consequence of the results achieved in the past 10 years and of the interest by patients, endocrinologists, and neurosurgeons. Furthermore, the special ability of the endoscope to offer a wider and detailed view of anatomic structures is a major advantage that increases the attention of neurosurgeons who seek less invasive procedures and better results. Most neurosurgeons performing transsphenoidal surgery, however, are not used to endoscopy, and changing from microsurgical to endoscopic technique can be difficult and even discouraging, often because of difficulties in the initial phase of the procedure. TECHNIQUE: With the purpose of helping minimize some of the difficulties, we describe herein useful tips and tricks that mainly concern familiarization with the endoscopic equipment, details of the transsphenoidal anatomy, and endoscopic skills. We stress the steps and details that we judge most important. CONCLUSION: We believe that by following these recommendations neurosurgeons can overcome, or even avoid, the difficulties frequently encountered transsphenoidal surgery, allowing them to safely and efficiently perform endonasal transsphenoidal endoscopic procedures. PMID- 17350398 TI - Minimally invasive lumbar laminectomy via a dual-tube technique: evaluation in a cadaver model. AB - BACKGROUND: Minimally invasive surgery is a promising new tool in treatment of spinal disorders. Minimally invasive laminectomy provides an efficacious means of achieving lumbar decompression. Present single-tube approaches may entail significant facet injury. We explore the feasibility of a dual-tube minimally invasive laminectomy approach in a cadaver model. METHODS: We performed minimally invasive lumbar laminectomies in 8 adult cadavers. Twenty-three levels were treated. We used a dual-tube technique, undercutting the facet joints bilaterally while attempting to minimize facet injury. Crossed-tube rongeuring of individual facet joints and neural foramina mirrored open techniques. Pre- and postoperative CT scans of the cadavers were obtained; we measured the cross-sectional area of the spinal canal and neural foramina in each specimen using a CT workstation. Facet damage was assessed. We used the Medtronic Sofamor-Danek (Memphis, Tenn) X Tube and Quadrant systems to complete individual procedures. RESULTS: Increases in canal cross-sectional area were achieved in each specimen: L3-4 increased from 238.3 to 354.4 mm(2) (125.1%); L4-5, 274 to 390.9 mm(2) (142.7%); and L5-S1, 349.9 mm(2) to 458.8 mm(2) (131%). Neural foraminal diameter also increased in each specimen (L3-4 right increased 123%; left, 136.8%; L4-5, 143.5% and 145.6%; L5-S1, 124% and 116% respectively). Incidental facet injury was noted in 5 (10.9%) of a potential 46 joints. CONCLUSIONS: We demonstrate that a dual-tube MIS technique can effectively complete lumbar decompressive laminectomy and foraminotomy procedures in a cadaver model, without significant facet injury. Minimally invasive surgery laminectomy techniques hold significant clinical promise. PMID- 17350399 TI - Electroencephalogram in head injury: promising new insights. PMID- 17350400 TI - Cortical synchrony changes detected by scalp electrode electroencephalograph as traumatic brain injury patients emerge from coma. AB - BACKGROUND: Recent studies show conscious perception is correlated with firing rate synchronization across multiple neuronal assemblies. This study explores the synchrony between multiple cortical surface sites as brain injury patients emerge from coma. METHODS: Scalp electrode EEG recordings were collected and analyzed from 13 traumatic brain injury patients during their stay in a neurosurgical intensive care unit. Neuronal synchrony was calculated between various electrode pairs during comatose and conscious periods defined by the GCS. Frequency bands from 1 to 30 Hz were evaluated in each patient. RESULTS: As patients emerged from coma at GCS 3 to GCS scores > or =8, synchrony values from all electrode pairs revealed a global decrease in synchrony at higher GCS scores. No significant effects were detected relative to the amount of sedation given, but at higher GCS scores significantly increased neuronal synchrony was observed between occipital lobes and right parietal and temporal lobe sites. Synchrony was decreased between frontal-occipital, frontal-parietal, and parietal-occipital electrodes. CONCLUSIONS: In frequencies from 1 to 30 Hz, synchrony between right parietal and temporal lobes, as well as bilateral occipital lobes, tends to be increased as patients emerge from comatose states. However, synchrony between most intrahemispheric cortical sites is decreased at higher GCS scores in most of the above frequency bands. Thus, brain injury patients demonstrate both increased and decreased cortical surface synchrony between different lobes during emergence from coma. PMID- 17350401 TI - Efficacy and complications of patient-controlled analgesia treatment after spinal surgery. AB - BACKGROUND: Postoperative pain is one of the most common therapeutic problems in hospitals. Patient-controlled analgesia has gained popularity over the last decade in dealing with this problem. The goal of this article is to examine the effect of PCA in patients who underwent spinal fusion and to measure its effect on the different sexes and age groups. METHODS: Two hundred thirty-seven patients who underwent spinal fusion for lumbar instability at our institution comprise this study. All patients received PCA in a certain protocol. Pain was measured according to the VAS, and any complications due to the use of PCA were recorded. RESULTS: Patient-controlled analgesia reduced the VAS in all age groups. Reduction in VAS was higher in the age group of 60 years or more. No significant differences in VAS reduction were noted between males and females. In 40% of our patients, complications were recorded. Eight percent reported more than 1 complication. However, these complications were nonfatal, and all patients responded well to conservative treatment. On termination of the study, most patients (213/237) were satisfied with the PCA procedure for reducing their pain. CONCLUSION: We conclude that PCA is an effective and safe method with high satisfaction rate in postoperative pain control in patients who undergo spinal fusion. PMID- 17350403 TI - Chronic subdural hematomas--causes of morbidity and mortality. AB - OBJECTIVE: Chronic subdural hematoma is a very common condition seen usually in the later stages of life. Treatment, although apparently simple, is associated with some morbidity and mortality with a potential for recurrence. This is especially important as the average life span of humanity increases all over the world. METHODS: A retrospective analysis of 647 cases of chronic subdural hematomas treated in NIMHANS was done. The aim of this study was to determine the factors responsible for the morbidity, mortality, and recurrence in patients with chronic subdural hematomas. RESULTS: The patients were mostly men in the sixth and seventh decade of life and presented with headache, cognitive decline, or focal deficits. CT scan was done in all cases. 94% of the patients underwent evacuation of the hematoma. There was a mortality rate of 5%, and there was a recurrence of 21%. Statistical analysis for factors both for mortality and morbidity were done. CONCLUSIONS: It was seen that statistically significant factors determining mortality were age, GCS at presentation, and associated illnesses like cardiac and renal failure. The statistically significant factors for recurrence are the presence of a thick subdural membrane visualized during surgery and brain, remaining at a depth at the end of evacuation of hematoma. Use of a subdural drain significantly reduced recurrences. The chronicity of the hematoma was not a factor determining mortality or morbidity. Drains were seen to significantly reduce recurrence in younger patients with better GCS and when the subdural membrane is seen at surgery and the brain remains at a depth at the end of hematoma evacuation. PMID- 17350406 TI - Membranectomy in organized chronic subdural hematomas: indications and technical notes. AB - BACKGROUND: The aim of the present study is to present our operative method of removing organized CSDHs and to structure the criteria for choosing this approach as first treatment. METHODS: Between 1991 and 1999 at our Institution, 14 consecutive patients with organized CSDHs required 16 craniotomies with membranectomy. They represent 5.8% of all patients (243) treated for CSDHs in the same period. All the patients had preoperative contrast-enhanced CT, and 9 patients also had contrast MRI. RESULTS: Initially, 9 patients underwent one burr hole or twist-drill hole. Of these 9 patients, 3 were treated at the same surgery with craniotomy and membranectomy as second treatment, 3 underwent a second burr hole and then membranectomy at the same surgery, and 3 patients underwent a second burr hole 3, 4, and 21 days after the first one and then membranectomy. Five patients underwent immediate craniotomy and membranectomy. There were no morbidity or mortality associated with this procedure. All patients had a full recovery without recurrence. CONCLUSIONS: Contrast-enhanced MRI has greatly improved opportunities for discovering neomembrane before surgical intervention. We believe that MRI detection of thick and extensive membranes or solid clot with mass effect makes an immediate craniotomy to remove CSDH necessary. PMID- 17350409 TI - Differentiation between intradural and extradural locations of juxta-dural ring aneurysms by using contrast-enhanced 3-dimensional time-of-flight magnetic resonance angiography. AB - BACKGROUND: Juxta-dural ring aneurysms of the ICA have different clinical outcomes and risks for SAH, which are dependent on their position in the intradural or extradural space. The aim of this study was to reveal the precise location of such aneurysms by using CE-MRA. METHODS: Contrast-enhanced MRA studies were performed in 21 patients with 24 juxta-dural ring aneurysms. The locations were evaluated by source images of CE-MRA and MPR images. We evaluated the accuracy of preoperative MRI findings by comparing imaging results with intraoperative findings in 7 cases. RESULTS: The CS was clearly enhanced in the CE-MRA technique, which allowed the precise identification of these aneurysms as intradural or extradural. Intracavernous aneurysms were diagnosed when the greater hyperintensity of the aneurysm was located within the less hyperintense region of the contrast-enhanced CS. Nine of the cases were diagnosed as intradural aneurysms, and 15 aneurysms were noted as extradural based on the findings of CE-MRA. Surgery was performed in 7 cases, which included 4 intradural and 3 extradural aneurysms, and the preoperative MRI findings corresponded with the intraoperative findings in all cases. CONCLUSION: Contrast-enhanced MRA and MPR are very useful techniques for determining the location of juxta-dural ring aneurysms. PMID- 17350410 TI - Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme. AB - BACKGROUND: Results of the current therapy for GBM are dismal; the mean survival time of patients is approximately 1 year-and it has been so for several decades. In preliminary studies, we have observed a potentiating therapeutic effect when chloroquine was added to the conventional treatment of GBM. METHODS: Over the last 5 years, 41 patients with GBM received chloroquine as an optional adjuvant administered concurrently with conventional surgery, chemotherapy, and radiotherapy. These patients did not participate in our previous studies on chloroquine administration and were studied retrospectively; 82 contemporary patients with GBM who did not receive chloroquine were included in this analysis as control subjects. The end point observed was time of survival after surgery. RESULTS: Survival time in patients treated with chloroquine was 25 +/- 3.4 months, as compared with that of 11.4 +/- 1.3 months in control subjects (P = .000; OR = 0.4; 95% CI = 0.26-0.6); the difference remained significant after regression analysis for possible clinical confounders. CONCLUSIONS: In agreement with our recent reports, chloroquine exerts a strong adjuvant effect when added to the conventional treatment of GBM. In this large cohort of unselected patients with GBM who were treated with chloroquine, the median survival time doubled as compared with that of control subjects. PMID- 17350411 TI - A novel microsurgical technique reduces hand tremor in the course of lateral suboccipital approach. AB - BACKGROUND: The physiological tremor may cause difficulties in microsurgery. The arm rest and the support of the outside hand edge on the skull reduces the tremor to 10th proportion at the end of the microsurgical instruments. METHODS: The new fingertip support technique consists of the I-III finger support, which holds the instruments, on the bridge (Bethlehem bridge) above the operation area. This technique shows the method at the lateral suboccipital approach. RESULTS: The tremor at the end of the instruments is effectively reduced. CONCLUSION: By this technique the microsurgical work may became more precise. PMID- 17350413 TI - Hiccup and neurosurgeons: a report of 4 rare dorsal medullary compressive pathologies and review of the literature. AB - OBJECTIVE: The aim of this study was to present 4 rare cases of medullary compressive lesions presenting with IH, to discuss the indications for neurosurgical decompression in such cases, and to review the possible etiologies of IH briefly. METHODS: The reported cases include (1) a 19-year-old adolescent boy and a 21-year-old man with Chiari I malformation and cervical syrinx compressing or tightening the cervico-medullary junction; (2) a 35-year-old man with ependymoma extending from the lower half of the fourth ventricle to C1/C2 junction and compressing this part of the medulla; and (3) a 16-year-old adolescent boy who was referred to the emergency department in severe distress because of IH, occurring as a result of a distal PICA aneurysm located on the floor of the lower triangle of the fourth ventricle. RESULTS: Surgical decompression in all the cases was successful in withholding the hiccups. CONCLUSION: The dorsal medullary area is not an unusual location for genesis of hiccup. When encountering a case of IH, appropriate CNS imaging studies should be included in the evaluation protocol. PMID- 17350415 TI - Primary treatment of an indirect carotid cavernous fistula by injection of N butyl cyanoacrylate in the dural wall of the cavernous sinus. AB - BACKGROUND: Carotid cavernous fistulae are abnormal communications between the carotid artery system and the cavernous sinus. Endovascular treatment is the treatment of choice, but because of their heterogeneous etiology and anatomy, an appropriate treatment plan must be tailored for each patient. CASE DESCRIPTION: A 77-year-old diabetic woman presented with rapid onset of right eye pain, conjunctivitis, and chemosis. Angiography revealed an indirect CCF located in the posterior wall of the right cavernous sinus. N-Butyl cyanoacrylate was injected directly into the fistula site in the dural wall via a microcatheter, resulting in a cure. CONCLUSION: We describe an unconventional treatment of an indirect CCF from an IPS approach. One type D(2) CCF was treated successfully using only N butyl cyanoacrylate injected directly at the fistula site. This was achieved by microcatheterization of the fistula in the posterior wall of the right cavernous sinus. PMID- 17350417 TI - Difficulty in diagnosing a case with apparent sequel cerebral sparganosis. AB - BACKGROUND: We report on a case of cerebral sparganosis that was correctly identified by a biopsy 10 years after the initial infection. CASE DESCRIPTION: A 62-year-old man presented with an unusual case of cerebral sparganosis mansoni. He was admitted to our hospital for removal of a right frontal meningioma. Computed tomographic scan and MRI of the brain showed atrophy of the left cerebral hemisphere, enlargement of the lateral ventricle, and several small ring enhanced lesions in the left frontal lobe. The patient had suffered from motor aphasia and right hemiparesis for 10 years; in addition, he had been treated for cerebral infarction. We performed a left frontal biopsy, during which we also removed the meningioma. The histologic diagnosis was cerebral sparganosis mansoni. CONCLUSIONS: The follow-up CT findings after the patient's first attack were thought to be characteristic of cerebral sparganosis mansoni. However, the radiographic findings were difficult to differentiate from those of neoplasias. PMID- 17350419 TI - Surgery for mesencephalic cavernoma: case report. AB - BACKGROUND: Intrinsic midbrain tumor has been one of the most challenging therapeutic tasks in neurosurgery because of its prognosis and risks associated with surgical procedures. We encountered a rare case of cavernoma located in the anterior-mesencephalic region presented as parkinsonism tremor. CASE DESCRIPTION: A 42-year-old woman had a resting tremor for 10 years. This tremor involved the left shoulder and the proximal and distal limb, which was exacerbated by any attempted movement and became grossly uncontrollable. She showed a partial right ophthalmoplegia with mydriasis. Her right upper and lower extremities had normal strength, but her left extremities had three-fifth strength. Her sensation was intact. Magnetic resonance imaging demonstrated a popcorn-like rounded lesion in the right ventral midbrain adjacent to the medial cerebral peduncle. To access this anterior-medial portion of the midbrain, we chose a frontotemporal transsylvian route via an orbitozygomatic craniotomy. With a longitudinal pial incision between the frontopontine fibers and the pyramidal tracts in the peduncle, the cavernoma was totally removed en bloc. After the operation, the tremor dramatically disappeared. The muscle strength of her left lower extremity improved to four fifths, whereas the upper extremity was still the same. The preoperative left oculomotor palsy seemed to have no improvement. CONCLUSIONS: Clinically manifested cavernoma due to repeated hemorrhage needs surgical intervention. With an optimal surgical approach, fairly safe entry zones on the anterior face of the rostral brainstem may be accessible, which provides a successful resection of a mesencephalic cavernoma without postoperative complications. PMID- 17350421 TI - Delayed diagnosis of cerebellar hemangioblastoma after intracerebellar hemorrhage. AB - BACKGROUND: Cerebellar hemorrhage caused by cerebellar hemangioblastoma is not a frequent case. We report a case of solid, cerebellar hemangioblastoma, diagnosed 4 years after cerebellar hemorrhage. CASE DESCRIPTION: A 69-year-old man presented with dizziness and gait disturbance. He had a 4-year history of evacuation of cerebellar hemorrhage. Gadolinium-enhanced MRI revealed a well enhancing mass in the left cerebellar hemisphere, and vertebral angiography revealed hypervascularity. Radiotherapy was given to the tumor bed. He remained stable for more than a year after radiation. CONCLUSION: In cases of spontaneous cerebellar hemorrhage, particularly in the patient without hypertension or other underlying diseases related to bleeding from tumor, cerebellar hemangioblastoma should be suspected as a rare cause of hemorrhage, and computed tomography and/or MRI with contrast administration is mandatory for differential diagnosis. PMID- 17350422 TI - Chiari malformations in patients with uncorrected sagittal synostosis. AB - BACKGROUND: Single suture craniosynostoses were long considered a benign condition with little risk of complications. In many cases, parents may forego surgical correction because of the inherent risks of surgical intervention. CASE DESCRIPTION: We report 2 cases of uncorrected sagittal synostosis associated with the development of Chiari malformations with syringomyelia later in life. To our knowledge, this is the first report of symptomatic Chiari malformations associated with uncorrected sagittal synostosis. We discuss mode of presentation and management in each case. We propose that these patients either have a pathophysiological predisposition to Chiari malformations based on the compensatory bone growth pattern in sagittal synostosis resulting in craniocephalic disproportion or that there may be an underlying genetic alteration accounting for the association of the 2 processes. CONCLUSIONS: Further investigations are warranted to investigate whether the incidence of Chiari malformations is decreased in patients who have undergone early correction of an isolated sagittal synostosis. We conclude that patients with sagittal synostosis should be evaluated for Chiari malformations before being discharged permanently from a neurosurgical practice. PMID- 17350425 TI - Fidel Castro's medical care in the socialized Cuban paradise. PMID- 17350426 TI - Declining physician morale and some answers. PMID- 17350427 TI - Health care for US children. PMID- 17350428 TI - Modern day slavery. PMID- 17350429 TI - Neurological disease: time to reassess. PMID- 17350430 TI - Non-ST-elevation acute coronary syndromes. PMID- 17350431 TI - Can we RESOLVE the treatment of sepsis? PMID- 17350432 TI - Tracking inequity: assessments of poverty-related outcomes. PMID- 17350433 TI - Health as an instrument of foreign policy. PMID- 17350434 TI - Leprosy lessons from old bones. PMID- 17350437 TI - Clinical update: postoperative analgesia. PMID- 17350438 TI - Nahid Toubia. PMID- 17350440 TI - Developmental neurotoxicity of industrial chemicals. PMID- 17350441 TI - Developmental neurotoxicity of industrial chemicals. PMID- 17350443 TI - Age-proofing hospital surge capacity. PMID- 17350444 TI - Direct-to-consumer drug information in Europe. PMID- 17350446 TI - Screening for toxoplasmosis in pregnancy. PMID- 17350447 TI - Patient safety and patient error: the carer's perspective. PMID- 17350448 TI - Risk factors for adverse outcomes in developing countries. PMID- 17350449 TI - Early child development in developing countries. PMID- 17350450 TI - Coronary heart disease in Chile. PMID- 17350451 TI - Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study. AB - BACKGROUND: The ICTUS trial was a study that compared an early invasive with a selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS). The study reported no difference between the strategies for frequency of death, myocardial infarction, or rehospitalisation after 1 year. We did a follow-up study to assess the effects of these treatment strategies after 4 years. METHODS: 1200 patients with nSTE-ACS and an elevated cardiac troponin were enrolled from 42 hospitals in the Netherlands. Patients were randomly assigned either to an early invasive strategy, including early routine catheterisation and revascularisation where appropriate, or to a more selective invasive strategy, where catheterisation was done if the patient had refractory angina or recurrent ischaemia. The main endpoints for the current follow-up study were death, recurrent myocardial infarction, or rehospitalisation for anginal symptoms within 3 years after randomisation, and cardiovascular mortality and all-cause mortality within 4 years. Analysis was by intention-to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN82153174. FINDINGS: The in-hospital revascularisation rate was 76% in the early invasive group and 40% in the selective invasive group. After 3 years, the cumulative rate for the combined endpoint was 30.0% in the early invasive group compared with 26.0% in the selective invasive group (hazard ratio 1.21; 95% CI 0.97-1.50; p=0.09). Myocardial infarction was more frequent in the early invasive strategy group (106 [18.3%] vs 69 [12.3%]; HR 1.61; 1.19-2.18; p=0.002). Rates of death or spontaneous myocardial infarction were not different (76 [14.3%] patients in the early invasive and 63 [11.2%] patients in the selective invasive strategy [HR 1.19; 0.86-1.67; p=0.30]). No difference in all-cause mortality (7.9%vs 7.7%; p=0.62) or cardiovascular mortality (4.5%vs 5.0%; p=0.97) was seen within 4 years. INTERPRETATION: Long-term follow-up of the ICTUS trial suggests that an early invasive strategy might not be better than a more selective invasive strategy in patients with nSTE-ACS and an elevated cardiac troponin, and implementation of either strategy might be acceptable in these patients. PMID- 17350452 TI - Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. AB - BACKGROUND: Drotrecogin alfa (activated) (DrotAA) is used for the treatment of adults with severe sepsis who have a high risk of dying. A phase 1b open-label study has indicated that the pharmacokinetics and pharmacodynamics of DrotAA are similar in children and adults. We initiated the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE) trial to investigate the efficacy and safety of the drug in children. METHODS: Children aged between 38 weeks' corrected gestational age and 17 years with sepsis-induced cardiovascular and respiratory failure were randomly assigned to receive placebo or DrotAA (24 microg/kg/h) for 96 h. We used a prospectively defined, novel primary endpoint of Composite Time to Complete Organ Failure Resolution (CTCOFR) score. Secondary endpoints were 28-day mortality, major amputations, and safety. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov, number NCT00049764. FINDINGS: 477 patients were enrolled; 237 received placebo, and 240 DrotAA. Our results showed no significant difference between groups in CTCOFR score (p=0.72) or in 28-day mortality (placebo 17.5%; DrotAA, 17.2%; p=0.93). Although there was no difference in overall serious bleeding events during the 28-day study period (placebo 6.8%; DrotAA 6.7%; p=0.97), there were numerically more instances of CNS bleeding in the DrotAA group (11 [4.6%], vs 5 [2.1%] in placebo, p=0.13), particularly in children younger than 60 days. For CTCOFR score days 1-14, correlation coefficient was 0.016 (95% CI -0.106 to 0.74); relative risk for 28-day mortality was 1.06 (95% CI 0.66 to 1.46) for DrotAA compared with placebo. INTERPRETATION: Although we did not record any efficacy of DrotAA in children with severe sepsis, serious bleeding events were similar between groups and the overall safety profile acceptable, except in children younger than 60 days. However, we gained important insights into clinical and laboratory characteristics of childhood severe sepsis, and have identified issues that need to be addressed in future trials in critically ill children. PMID- 17350453 TI - Ecological association between asbestos-related diseases and historical asbestos consumption: an international analysis. AB - BACKGROUND: The potential for a global epidemic of asbestos-related diseases is a growing concern. Our aim was to assess the ecological association between national death rates from diseases associated with asbestos and historical consumption of asbestos. METHODS: We calculated, for all countries with data, yearly age-adjusted mortality rates by sex (deaths per million population per year) for each disease associated with asbestos (pleural, peritoneal, and all mesothelioma, and asbestosis) in 2000-04 and mean per head asbestos consumption (kg per person per year) in 1960-69. We regressed death rates for the specified diseases against historical asbestos consumption, weighted by the size of sex specific national populations. FINDINGS: Historical asbestos consumption was a significant predictor of death for all mesothelioma in both sexes (adjusted R2=0.74, p<0.0001, 2.4-fold [95% CI 2.0-2.9] mortality increase was predicted per unit consumption increase for men; 0.58, p<0.0001, and 1.6-fold [1.4-1.9] mortality increase was predicted for women); for pleural mesothelioma in men (0.29, p=0.0015, 1.8-fold [1.3-2.5]); for peritoneal mesothelioma in both sexes (0.54, p<0.0001, 2.2-fold [1.6-2.9] for men, 0.35, p=0.0008, and 1.4-fold for women [1.2-1.6]); and for asbestosis in men (0.79, p<0.0001, 2.7-fold [2.2-3.4]). Linear regression lines consistently had intercepts near zero. INTERPRETATION: Within the constraints of an ecological study, clear and plausible associations were shown between deaths from the studied diseases and historical asbestos consumption, especially for all mesothelioma in both sexes and asbestosis in men. Our data strongly support the recommendation that all countries should move towards eliminating use of asbestos. PMID- 17350454 TI - Reductions in child mortality levels and inequalities in Thailand: analysis of two censuses. AB - BACKGROUND: Thailand's progress in reducing the under-five mortality rate (U5MR) puts the country on track to achieve the fourth Millennium Development Goal (MDG). Whether this success has been accompanied by a widening or narrowing of the child mortality gap between the poorest and richest populations is unknown. We aimed to measure changes in child-mortality inequalities by household-level socioeconomic strata of the Thai population between 1990 and 2000. METHODS: We measured changes in the distribution of the U5MR by economic strata using data from the 1990 and 2000 censuses. Economic status was measured using household assets and characteristics. The U5MR was estimated using the Trussell version of the Brass indirect method. FINDINGS: Average household economic status improved and inequalities declined between the two censuses. There were substantially larger reductions in U5MR in the poorer segments of the population. Excess child mortality risk between the poorest and richest quintile decreased by 55% (95% CI 39% to 68%). The concentration index, measured using percentiles of economic status, in 1990 was -0.20 (-0.23 to -0.18), whereas in 2000 it had dropped to 0.12 (-0.15 to -0.08), a 43% (22% to 63%) reduction. INTERPRETATION: These findings draw attention to the feasibility of incorporating equity measurement into census data. Thailand has achieved both an impressive average decrease in U5MR and substantial reductions in U5MR inequality over a 10 year period. Contributing factors include overall economic growth and poverty reduction, improved insurance coverage, and a scaling-up and more equitable distribution of primary health-care infrastructure and intervention coverage. Understanding the factors that have led to Thailand's success could help inform countries struggling to meet the fourth MDG and reduce inequality. PMID- 17350455 TI - Shock and stony hard ears. PMID- 17350456 TI - Health is global: proposals for a UK Government-wide strategy. AB - Global health enables the harmonisation of international and domestic-health concerns-its outlook is much wider than a development or foreign-assistance perspective alone. Engaging globally in health requires the creation of relevant and effective partnerships to implement solutions for shared or common problems. To build on the UK's achievements and leadership in global health, the central government Department of Health is now leading the development of a UK Government wide global strategy. This paper describes the rationale and process for developing the new UK Government-wide strategy for global health and highlights some of the issues that must be discussed. PMID- 17350457 TI - Towards good practice for health statistics: lessons from the Millennium Development Goal health indicators. AB - Health statistics are at the centre of an increasing number of worldwide health controversies. Several factors are sharpening the tension between the supply and demand for high quality health information, and the health-related Millennium Development Goals (MDGs) provide a high-profile example. With thousands of indicators recommended but few measured well, the worldwide health community needs to focus its efforts on improving measurement of a small set of priority areas. Priority indicators should be selected on the basis of public-health significance and several dimensions of measurability. Health statistics can be divided into three types: crude, corrected, and predicted. Health statistics are necessary inputs to planning and strategic decision making, programme implementation, monitoring progress towards targets, and assessment of what works and what does not. Crude statistics that are biased have no role in any of these steps; corrected statistics are preferred. For strategic decision making, when corrected statistics are unavailable, predicted statistics can play an important part. For monitoring progress towards agreed targets and assessment of what works and what does not, however, predicted statistics should not be used. Perhaps the most effective method to decrease controversy over health statistics and to encourage better primary data collection and the development of better analytical methods is a strong commitment to provision of an explicit data audit trail. This initiative would make available the primary data, all post-data collection adjustments, models including covariates used for farcasting and forecasting, and necessary documentation to the public. PMID- 17350458 TI - Ancillary-care responsibilities in observational research: two cases, two issues. PMID- 17350459 TI - Neurosarcoidosis: a treatable cause of vestibular dysfunction. PMID- 17350460 TI - Loss of heterozygosity and microsatellite instability on chromosome arm 10q in neuroblastoma. AB - Tumor suppressor genes can be inactivated by various mechanisms, including promoter hypermethylation and loss of heterozygosity. We screened the 10q locus for loss of heterozygosity and the promoter methylation status of PTEN, MGMT, MXI1, and FGFR2 in neuroblastic tumors and neuroblastoma cell lines. Expression of these genes in cell lines was analyzed with reverse transcriptase-polymerase chain reaction. Loss of heterozygosity at 10q was detected in 18% of tumors and microsatellite instability in 14%. Promoter hypermethylation of MGMT appeared in 8% of tumors and 25% of cell lines. Correlation between methylation status and lack of expression was evident for PTEN, FGFR2, and MXI1 and was less clear for MGMT. No associations between these alterations and MYCN amplification, 1p deletion, or aggressive tumor histology could be demonstrated, singly or in combination. These data suggest that 10q alterations might be implicated in the development of a small number of neuroblastomas. PMID- 17350461 TI - Allelic losses at genomic instability-associated loci in villous adenomas and adjacent colorectal cancers. AB - Allelic imbalances in premalignant villous adenomas were compared with those in adjacent microdissected colorectal carcinoma that had arisen directly from the adenomas. Carcinoma-adenoma pairs were examined from 17 patients who underwent resections for colorectal cancer. In all, 28 microsatellite markers were examined, from regions of the genome where individual allelic losses have been associated with overall genomic instability in colorectal carcinomas. Microsatellite instability (MSI) was also evaluated for each marker in each tissue type. Loss of heterozygosity for multiple markers was found in 35% of adenomas and 65% of carcinomas; the average fractional allelic loss rate was 2.5 times higher in carcinomas than in adenomas. Of the 17 patients, 4 had MSI for >30% of markers in both adenoma and carcinoma, with no significant differences between the two tissues. Markers with particularly high imbalance rates in adenomas were seen on chromosomes 11, 14, and 15. These findings provide further evidence that genomic instability is an ongoing process during carcinogenesis, with a markedly increased frequency of allelic losses seen in carcinomas, compared with adjacent adenomas. Markers on chromosomes 11, 14, and 15 may become valuable tools in the identification of patients destined to progress to colorectal carcinomas. PMID- 17350462 TI - Lipocalin 24p3 is regulated by the Wnt pathway independent of regulation by iron. AB - Lipocalin 24p3 plays a direct role in iron transport and regulates the levels of important proteins of the iron metabolism. Iron-loaded 24p3 binds to its specific receptor (24p3R) on the cell surface. Upon binding to its receptor, 24p3 is internalized into the cell, where it releases its bound iron. Iron-free 24p3 can withdraw iron from inside the cell to the outside by a reverse mechanism. We analyzed the role of the murine 24p3 gene Lcn2 (alias 24p3) as a target of the Wnt pathway. In cells with activated Wnt pathway, the levels of 24p3 protein and RNA were decreased. The withdrawal of iron led to 24p3 downregulation, and iron addition to iron-deprived cells induced 24p3 expression. Despite its strong inhibitory effect on 24p3 expression, Wnt pathway activation had no effect on the intracellular iron level. In cells with nonactivated Wnt pathway, we found an as yet unidentified transcript of 24p3R. Our results indicate independent regulation of 24p3 expression by the Wnt pathway and by the intracellular iron level. Differential splicing of the 24p3R transcript, depending on the activation state of the Wnt pathway, may modify the function of 24p3. PMID- 17350463 TI - Haploinsufficiency of 8p22 may influence cancer-specific survival in prostate cancer. AB - Although Knudson's two-hit hypothesis with functional loss of a tumor suppressor gene has been widely accepted, accumulating evidence suggests that several genes are regulated by the quantity of their product in a dose-dependent manner (gene dosage effect). The study was designed to identify the influence of gene dosage effect of 8p22 on patient prognosis. With a median age of 71 years, 40 patients with prostate cancer (11 organ-confined, 13 capsular penetrating, and 16 nodal and/or distant metastatic) were followed for a median of 68.5 months. A fluorescence in situ hybridization (FISH) technique was applied using a region specific cosmid probe combined with centromeric probe. Allelic losses of 8p22, 8p21.3, 8p21.1 approximately 2, and 8p12 were found in 23, 22, 14, and 9 patients, respectively. A Cox proportional hazard model revealed that decreased fraction (i.e., the fraction of nuclei with a lesser number of cosmid signals than of centromeric probe signals) of 8p22 proved to be the sole independent prognostic factor predicting cancer-specific death, as well as disease progression--but allelic loss of 8p22 was not predictive. Cytogenetic estimation of 8p22 by FISH can yield quantitative evaluation of relevant gene dosage, which may become a useful biomolecular marker predicting poor patient prognosis. PMID- 17350464 TI - Characterization of trisomy 8 in pediatric undifferentiated sarcomas using advanced molecular cytogenetic techniques. AB - Pediatric undifferentiated soft tissue sarcomas (USTS) are a rare group of neoplasms that are unclassifiable despite the application of immunohistochemical, cytogenetic, and molecular techniques. To date, there is a dearth of studies looking at the cytogenetic and molecular genetic alterations in such tumors. Trisomy 8, a frequent molecular alteration in neoplasia, is seen in several soft tissue sarcomas, including Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), synovial sarcoma, and leiomyosarcoma. Because USTS share several clinicobiological features with the aforementioned tumors, the occurrence of alterations in chromosome 8 was studied in 11 pediatric USTS using a combination of interphase fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and genomic profiling with oligonucleotide array comparative genomic hybridization (aCGH). The copy number status of MYC was also assessed on the same tumors using dual-color FISH, with the aim of delineating the degree and intratumoral distribution of MYC amplification in this tumor. A near-uniform presence of an increase in MYC copy number was observed, along with an increase in chromosome 8 copy number in all the tumors. SKY and aCGH analysis of tumors exhibiting trisomy 8 confirmed the numerical imbalances. The occurrence of trisomy 8 in a subset of pediatric USTS confirms a shared genomic alteration with several other soft tissue sarcomas. Further studies are required to determine the clinical implications of such a finding. PMID- 17350465 TI - Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer. AB - BUBR1, a mitotic checkpoint protein, is a key component of the mitotic spindle checkpoint machinery. Defective BUBR1 has been proposed to contribute to chromosomal instability (CIN). To elucidate the relationship of BUBR1 expression with CIN, expression of BUBR1, numbers of centrosomes, numerical aberrations of chromosomes, and DNA ploidy were examined, and BUBR1 expression status was compared with clinicopathological parameters in 104 human urothelial bladder carcinomas. Expression of BUBR1 and numbers of centrosomes were assessed by immunohistochemistry. Numerical aberrations of chromosomes 7, 9, and 17 were evaluated by fluorescence in situ hybridization. Cancers with a large intercellular variation in centromere copy number were designated as CIN cancers. Tumors with BUBR1 overexpression were associated with CIN, DNA aneuploidy, and centrosome amplification. Array CGH revealed that BUB1B amplification and loss rarely occurred, indicating that the overexpression of BUBR1 in these bladder cancers was independent of BUB1B copy number. Overexpression of BUBR1 significantly correlated with higher histological grade, advanced pathological stage, and high cell proliferation. Overexpression of BUBR1 predicted tumor recurrence and disease progression. These data suggest that overexpression of BUBR1 is potentially a new tumor marker for estimating biological characteristics of bladder cancer. PMID- 17350466 TI - Novel chromosomal aberrations in a recurrent malignant meningioma. AB - The molecular basis of tumorigenesis and tumor progression in meningiomas is not fully understood. Here we present results of conventional cytogenetic, fluorescence in situ hybridization (FISH), and comparative genetic hybridization (CGH) analyses in a patient with recurrent anaplastic meningioma. We found complex aberrant karyotype alterations previously described in anaplastic meningiomas, such as 1p, 14q aberration, and a possibly tetraploid karyotype. Loss of chromosome 22q was detected by conventional cytogenetic analysis. Additional chromosomal aberrations not previously reported included a near triploid karyotype and alterations such as 4p+, 5p-, 7p+, 8q+, and gain of chromosome 19. FISH with LSI 9p21, CEP9, LSI PML/RARA, and CGH confirmed the karyotype complexity in this case. Our findings of several previously unreported cytogenetic alterations suggest that complex karyotype alterations are a characteristic feature in anaplastic meningiomas. High chromosomal complexity might be associated with a highly aggressive meningioma phenotype. PMID- 17350467 TI - An inv(16) in Ph-negative cells of a chronic myelogenous leukemia patient after imatinib treatment. AB - Secondary chromosomal changes are known to develop in Philadelphia chromosome negative (Ph-) cells of chronic myelogenous leukemia (CML) patients after treatment with imatinib mesylate, an ABL kinase inhibitor. We report here a novel case of a pericentric inversion of chromosome 16 as the sole cytogenetic abnormality in Ph- cells after treatment of Ph+ CML with imatinib. PMID- 17350468 TI - Translocations as a mechanism for homozygous deletion of 13q14 and loss of the ATM gene in a patient with B-cell chronic lymphocytic leukemia. AB - Chromosomal aberrations detected by fluorescence in situ hybridization (FISH) on interphase nuclei are important prognostic markers in chronic lymphocytic leukemia (CLL). Deletions in 13q14 and in 11q22.3 are two of the most frequent aberrations in this disease entity (55 and 18%, respectively) and are usually effected by interstitial deletions. Here, we report on the case of a 66-year-old woman with CLL who was analyzed by conventional metaphase cytogenetics as well as fluorescence in situ hybridization. Deletion-specific probes detected a homozygous loss of two anonymous loci in chromosomal band 13q14 in parallel with a heterozygous loss of the ATM gene located in chromosomal band 11q22.3. Karyotype analysis indicated reciprocal but unbalanced translocations involving chromosomes 3, 11, and 13. Deleted sites on 13q14 appeared to be located within the breakpoint regions of the translocations. We show that mechanisms other than interstitial deletions may lead to loss of critical chromosomal regions in CLL. PMID- 17350469 TI - Late-appearing pseudocentric fission event during chronic myeloid leukemia progression. AB - Pseudocentric fission is a rare event consisting of the splitting of one functional centromere into two new products, of which only one can give rise to a functionally competent kinetochore. We report here a pseudocentric fission event within the D5Z2 alphoid subset disrupting the centromeric region of chromosome 5 in a case of chronic myeloid leukemia (CML) after treatment with imatinib and interferon. The breakage generated unequal partitioning of alpha-satellite sequences between the two fission products. One product was inserted within the long arm of chromosome 12 at band 14.3, becoming the only functional centromere of chromosome der(5). The other fission product was rearranged to form a sandwich like dicentric--but functionally monocentric--chromosome der(6), made up of material from chromosomes 5, 12, and 6. The intercentric distance on der(6) was shown to be largely >20 Mb. To our knowledge, this is the first pseudocentric fission event described in CML. Moreover, our results confirm the susceptibility to breakage of the centromeric region of chromosome 5. PMID- 17350470 TI - Embryonal rhabdomyosarcoma with a der(16)t(1;16) translocation. AB - Embryonal rhabdomyosarcoma (ERMS) is the most common subtype of RMS that predominantly involves the genitourinary tract and the head and neck regions in children younger than 10 years of age. Cytogenetically, ERMS is most frequently hyperdiploid, with extra copies of chromosomes 2, 7, 8, 11, 12, 13, and 20. No consistent structural chromosomal alteration has been identified in ERMS. In contrast, a t(2;13)(q35;q14) or t(1;13)(q36;q14) corresponding to PAX3-FOXO1A (previously FKHR) and PAX7-FOXO1A gene fusions are considered tumor-specific anomalies for alveolar RMS (ARMS). Occasionally, a recurrent secondary structural rearrangement involving chromosomes 1 and 16 is seen in translocation-positive ARMS, a der(16)t(1;16) resulting in an imbalance of 1q and 16q material. Conventional cytogenetic analysis of an ERMS arising in the urinary bladder of a 22-month-old male child revealed this nonrandom secondary chromosomal aberration, der(16)(1;16)(q22;q24), in a hyperdiploid complement with extra copies of chromosomes 2, 7, 8, 10, 12, 13, 19, and 20. Subsequent analyses showed tumor cells to be negative for FOXO1A, PAX3, or PAX7 gene locus rearrangements (by fluorescence in situ hybridization) and also negative for PAX3-FOXO1A and PAX7 FOXO1A fusion transcripts (by reverse transcriptase-polymerase chain reaction). These results suggest that the unbalanced t(1;16) translocation may be seen in RMSs lacking a primary genetic rearrangement. PMID- 17350471 TI - Three-way translocation involving band 6q21 in an acute lymphoblastic leukemia. PMID- 17350472 TI - CytCD79a expression in acute leukemia with t(8;21): biphenotypic or myeloid leukemia? PMID- 17350473 TI - Aberration of 3q and monosomy 7 in a child with acute myelogenous leukemia. PMID- 17350474 TI - Novel three-way t(4;5;22)(q35;q31;q13) in acute megakaryoblastic leukemia. PMID- 17350476 TI - Vanadyl sulfate, taurine, and combined vanadyl sulfate and taurine treatments in diabetic rats: effects on the oxidative and antioxidative systems. AB - BACKGROUND: Vanadyl sulfate (VS) and taurine are two promising agents in the treatment of diabetes related to their antihyperglycemic, antihyperlipidemic, and hyperinsulinemic effects. Data about the effects of VS on the oxidant-antioxidant system is limited and controversial. However, taurine is a well-documented antioxidant agent and our aim was to investigate the effects of VS, taurine and VS and taurine combination on the oxidative-antioxidative systems in streptozotocin-nicotinamide (STZ-NA) diabetic rats. METHODS: Nicotinamide (230 mg/kg, i.p.) and streptozotocin (65 mg/kg, i.p.) were administered. VS (0.75 mg/mL) and taurine (1%) were added to drinking water for 5 weeks. Rats were divided as control (C), diabetes (D), diabetes+VS (D+VS), diabetes+taurine (D+T), diabetes+VS and taurine (D+VST). Plasma and tissue malondialdehyde (MDA) levels were measured by high-performance liquid chromatography and spectrophotometry, respectively. Paraoxonase and arylesterase activities were measured by spectrophotometric methods and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined using commercial kits. RESULTS: VS, taurine and VS and taurine combination treatments reduced the enhanced blood glucose, serum total cholesterol and triglyceride, tissue MDA and plasma MDA (except in the D+VS group) levels and increased the reduced serum insulin level, serum paraoxonase and arylesterase activities, GSH-Px activity and SOD activity (except in the D+VS group). CONCLUSIONS: The findings of the present study suggest that VS and taurine exert beneficial effects on the blood glucose and lipid levels in STZ-NA diabetic rats. However, VS might exert prooxidative or antioxidative effects in various components of the body and taurine and VS combination might be an alternative for sole VS administration. PMID- 17350475 TI - Ethanol-mediated oxidative changes in blood lipids and proteins are reversed by aspirin-like drugs. AB - BACKGROUND: Previous work from our laboratory revealed that administration of selected nonsteroidal anti-inflammatory drugs (NSAIDs)-aspirin, naproxen, nimesulide, and piroxicam-prevented some signs of oxidative stress produced in rat livers acutely intoxicated with ethanol. Our final aim was to pursue these advantageous effects of NSAIDs in humans in relation to opposing the oxidative action of ethanol. In preparation for these studies, we conducted a search for tissues that were more accessible than liver, such as plasma and blood cells. METHODS: Either ethanol (5 g/kg body weight) or an isocaloric amount of glucose from a 30% solution alone or combined with one of the NSAIDs was administered orogastrically to rats; animals were sacrificed 5 h later. RESULTS: Ethanol increased both protein carbonylation (PCO) and thiobarbituric acid reactive substances (TBARS) in isolated lymphocytes, increased proteolysis in isolated red blood cells (RBC), and decreased the pool of plasma amino acids. The NSAIDs employed reversed the ethanol-mediated rise in PCO in plasma, but with the exception of aspirin failed to prevent the ethanol-produced decrease in the amino acid serum pool. Additionally, the increase in TBARS and PCO promoted by ethanol in lymphocytes was reverted with aspirin. In contrast, ethanol-activated proteolysis was not modified by aspirin. CONCLUSIONS: The pro-oxidant effects of ethanol and certain beneficial actions of NSAIDs, especially those of aspirin, preventing these pro-oxidant effects can be followed in blood constituents of rats. Hence, these oxidative markers could be regarded as potential clinical monitors for ethanol-mediated oxidative stress. PMID- 17350477 TI - Suppressive effects of melatonin on amyloid-beta-induced glial activation in rat hippocampus. AB - BACKGROUND: Growing evidence indicates that activated glia, as a result of chronic inflammation, are associated with amyloid-beta peptide (Abeta) deposits in the brain of Alzheimer's disease (AD) patients. The purpose of the present study was to investigate, in vivo, the effects of melatonin on glia activation, which may contribute to improved learning and memory in amnesic rats induced by amyloid-beta peptide 25-35 (Abeta25-35). METHODS: We examined cognitive function using the Morris water maze test. Expression of interleukin 1alpha (IL-1alpha) or complement 1q (C1q) in rat hippocampal tissue was determined by immunohistochemistry. RESULTS: It was found that Abeta25-35 injected into rat hippocampus induced an impairment in learning and memory and a marked increase of positive glial cells expressing IL-1alpha and C1q in hippocampus, compared with the controls. This suggests that glial activation triggered by Abeta25-35 parallels the dysfunction of learning and memory. Melatonin, at doses of 0.01, 0.1, and 1 mg/kg (i.g. for 10 days), improved learning and memory of rats treated with Abeta25-35. Cells expressing IL-1alpha and C1q were significantly decreased in hippocampus by pretreatment with melatonin at doses of 0.1 mg/kg and 1 mg/kg, but not at the dose of 0.01 mg/kg. CONCLUSIONS: Our data indicate that melatonin inhibited expressions of proinflammatory factors, which may contribute to improvement of learning and memory function in AD. PMID- 17350478 TI - Effects of acetylcysteine and probucol on contrast medium-induced depression of intrinsic renal glutathione peroxidase activity in diabetic rats. AB - BACKGROUND: Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity. METHODS: Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ). RESULTS: We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD. CONCLUSIONS: These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity. PMID- 17350479 TI - Gene dosage is not responsible for the upregulation of MRP1 gene expression in adult leukemia patients. AB - BACKGROUND: Upregulation of multidrug resistance-associated protein (MRP1) gene has been detected in many in vitro systems and could be the basis of the drug resistance phenotype in vivo. Increase in gene dosage and overexpression are two major mechanisms for increasing MRP1 expression level. In many drug resistant cell lines, MRP1 gene amplification has been detected. However, it is not yet known whether gene amplification plays a role in inducing the multidrug resistance phenotype clinically. METHODS: To establish whether MRP1 gene copy number is a common feature of the upregulation of MRP1 expression in cancer patients, we studied the MRP1 gene copy number in leukemia patients by fluorescent in situ hybridization (FISH) and real-time PCR. This involved determination of the MRP1 gene copy number and mRNA level in the peripheral blood of 52 adult leukemic patients and ten healthy volunteers. The leukemic CCRF-CEM cell line (drug sensitive) and its drug-resistant subline CCRF-E1000, which has MRP1 overexpression, were used as controls. RESULTS: The MRP1 gene copy number in CCRF-CEM was normal but increased significantly in CCRF-E1000 cell line. However, in the presence or absence of MRP1 overexpression, increase in gene dosage was not detected in patients. CONCLUSIONS: Our data suggest that the increase in MRP1 gene dosage observed in resistant cell lines is not responsible for the upregulation of MRP1 expression in leukemic patients. PMID- 17350480 TI - Cytogenetic profile of childhood acute lymphoblastic leukemia in Oman. AB - BACKGROUND: Chromosomal abnormalities have important diagnostic and prognostic significance in acute lymphoblastic leukemia (ALL). The purpose of this study was to define and classify the frequency and type of chromosomal abnormalities among newly diagnosed children with ALL and compare the results with those reported from other geographical regions of the world. METHODS: Bone marrow chromosomal studies with GTG banding were performed in untreated ALL pediatric patients aged from 7 days to 14 years. RESULTS: Among Omani children examined with ALL, 47 (81%) patients yielded results, with 26 (55.3%) showing an abnormal karyotype [10 (21.3%) pseudodiploid, 2 (4.3%) hypodiploid and 14 (29.7%) hyperdiploidy] and 21 (44.6%) had normal diploidy. Structural abnormalities were observed in 16 (34%), of which 11 (23.4%) cases were translocations, the most frequent being t(9;22) observed in three (6.4%) of our patients. Uncommon translocations such as t(9;15)(p11;q10), t(3;6)(p12;q11), t(1;6)(?31;?q23), t(1;19)(q12;q12), der(18)t(12;18)(q11;p11), and other structural aberrations add(2)(q22), add(6)(q16), add(18)(q22), add(14)(q32) along with deletions del(10)(q22), del(12)(p11), del(12)(p12), del(18)(q11) were also observed. CONCLUSIONS: The study showed a good correlation and concordance between the ploidy distribution by cytogenetics and flow cytometry. The patterns of chromosomal anomalies in our patients showed some variations in the frequency of aberrations reported. It is therefore necessary that newer techniques like fluorescence in situ hybridization (FISH) along with reverse transcriptase polymerase chain reaction (RT-PCR) and spectral karyotyping will help us identify chromosomal aberrations not detected by conventional cytogenetic methods in the near future. To our knowledge, this is the first report from the Middle East of a cytogenetic study on childhood ALL. PMID- 17350481 TI - Allopurinol as adjunctive therapy in intractable epilepsy: a double-blind and placebo-controlled trial. AB - BACKGROUND: Adenosine has been proposed to be an endogenous anticonvulsant agent. It inhibits glutamate release from excitatory neurons and neuronal firing. Therefore, adenosine agonists have potential clinical application as antiepileptics. In this double-blind randomized, placebo-controlled trial, we assessed the antiepileptic effect of allopurinol as an adjuvant agent in 38 patients with refractory epilepsy. METHODS: Thirty eight patients were randomly allocated equally to allopurinol+preexisting antiepileptic (Group A) or placebo+preexisting antiepileptic (Group B) for a 6-month, double-blind, placebo controlled study. The dose of allopurinol was titrated up to 300 mg/day (100 mg TDS). The dose of preexisting medications was maintained without change over the trial. The effect of allopurinol was evaluated by a reduction in the total number of seizures per month and duration of seizure attacks. RESULTS: Of 38 participants, 32 patients completed the study. There were significant differences between the two groups in terms of reduction in the total number of seizure over the trial. Seizures reduction of >30% in 66%, >50% in 55%, and >60% in 44% of cases in the allopurinol group was achieved after 2 months and persisted during the study. Nevertheless, only during month 4 was there a significant difference between the two groups regarding reduction in seizure duration. In the allopurinol group, two patients had transient rashes, two patients had mild nausea, and two experienced dizziness, but only one patient discontinued the drug due to dizziness. In the placebo group, one patient had rash and one patient had nausea. In addition, no significant hematological or hepatic changes were found during the trial in both groups. CONCLUSIONS: The results suggest allopurinol as a safe and effective adjuvant agent in refractory epilepsy. Based on this study, we suggest that purine metabolism pathways and the specific use of allopurinol should be further investigated with regards to neurobiology and treatment of refractory epilepsy. PMID- 17350482 TI - Helicobacter pylori in bronchiectasis: a polymerase chain reaction assay in bronchoalveolar lavage fluid and bronchiectatic lung tissue. AB - BACKGROUND: A number of studies have implicated an association between H. pylori and diverse extra-gastroduodenal pathologies. Chronic inflammation and increased immune response have been observed in bronchiectasis, likely gastroduodenal inflammatory diseases. H. pylori has been found in the trachea-bronchial aspirates of mechanically ventilated patients. Furthermore, the seroprevalence of H. pylori was found to be significantly higher in patients with bronchiectasis than in the control group. The present study was performed to investigate the possible role of H. pylori in the pathogenesis of bronchiectasis. METHODS: Prospectively, bronchoalveolar lavage fluid (BALF) was obtained from patients with bronchiectasis (n=26) and control (n=20). BALF was subjected to polymerase chain reaction (PCR) to determine the presence of H. pylori and serum IgG against H. pylori was determined with micro-ELISA kit. In addition, PCR was performed to determine H. pylori in surgically removed lung tissues from patients with bronchiectasis (n=97). RESULTS: H. pylori DNA was not detected in the BALF or in lung tissue samples. In addition, anti-H. pylori IgG level in patients with bronchiectasis did not show statistically significant difference from that of the control. CONCLUSIONS: Our study provided evidence that there might be no direct association between H. pylori and bronchiectasis; however, the indirect role of soluble products of H. pylori could not be excluded. PMID- 17350483 TI - Progressive impairment of autonomic control of heart rate in patients with multiple sclerosis. AB - BACKGROUND: Data regarding the autonomic control of heart rate in multiple sclerosis (MS) patients depending on the disease duration are lacking in the literature. The goal of this study was to evaluate differences in heart rate variability (HRV) in patients with MS according to the duration of the disease. METHODS: The study included 39 patients (23 female and 16 male; median age 42 years, range 34-53 years) with relapsing-remitting MS (RRMS) in stable phase and 39 age- and sex-matched healthy controls. RRMS patients were divided into two groups: group 1 with 21 patients within 5 years and group 2 with 18 patients with >5 years from the diagnosis of MS. HRV analysis was done with 24-h Holter ECG. RESULTS: Patients with RRMS had a significantly lower overall HRV than controls: SDNN 91+/-18 msec vs. 135+/-24 msec, p<0.001. RRMS patients with lower duration of disease (Group 1) had all higher HRV parameters except LF/HF ratio compared with RRMS patients with >5 years from the diagnosis of MS (Group 2): SDNN 94+/-24 vs. 88+/-21 msec, p=0.008; TP 2028+/-1326 vs. 1683+/-1017 ms2, p=0.006. CONCLUSIONS: Results of the study suggested that the autonomic control of heart rate depends on the disease duration in RRMS patients. Longer disease duration led to progressive impairment of cardiac autonomic balance in MS patients. PMID- 17350484 TI - Relationship between pericardial fluid B-type natriuretic peptide and ventricular structure and function. AB - BACKGROUND: We undertook this study to investigate the levels of pericardial B type natriuretic peptide (BNP) and its relationship with ventricular structure and function. METHODS: Pericardial and plasma BNP concentrations were measured in 18 patients with congenital ventricular septal defect. RESULTS: The mean level of BNP in the pericardial fluid (324.8+/-137.3 pg/mL) was higher than the plasma (20.8+/-6.1 pg/mL) (p=0.03). Pericardial BNP was correlated with the plasma BNP (r=0.85, p<0.01). A good correlation was also found between the pericardial BNP and left atrial diameter, left ventricular end-diastolic and end-systolic diameter, left ventricular ejection fraction, right ventricular diameter and pulmonary artery systolic pressure (p<0.05). CONCLUSIONS: The levels of BNP in pericardial fluid were higher than in the plasma. Similar to plasma BNP, pericardial BNP is also related to the ventricular structure and function. PMID- 17350485 TI - Influence of glucose in the dialysate on the activity of erythrocyte-glutathione peroxidase and blood selenium concentration in hemodialyzed patients. AB - BACKGROUND: The aim of the study was to show the influence of glucose in the dialysate on the intensity of oxidative stress, activity of glutathione peroxidase (GSHPx) and concentration of selenium in patients undergoing regular hemodialysis. METHODS: The study was comprised of 85 patients hemodialyzed with dialysate containing glucose [HD-g(+)] or not containing glucose [HD-g(-)], patients with chronic renal failure on conservative treatment and control group. The concentrations of the products of reaction with thiobarbituric acid (TBARS), concentration of selenium in erythrocytes and plasma, concentration of copper in erythrocytes and the activity of GSHPx were determined. RESULTS: GSHPx had significantly higher activity in HD-g(-) group before HD than in control group. In HD-g(+) group before hemodialysis, the activity of GSHPx was significantly lower than in the control group. After HD, the activity showed a statistically significant increase. In both hemodialyzed groups, selenium concentration before hemodialysis both in plasma and erythrocytes was significantly lower, compared to control group. In the group of patients with CRF on conservative treatment, selenium concentration in RBC was significantly higher, compared to concentrations obtained in other groups except for control group. The increase of copper concentration in erythrocytes was accompanied by the increase of oxidative stress and increase of TBARS concentration. The opposite relationship was observed for selenium-its concentration was inversely correlated to copper concentration. CONCLUSIONS: In both groups of hemodialyzed patients, hemodialysis caused the increase of GSHPx in erythrocyte activity and increase of plasma and erythrocyte selenium concentration. PMID- 17350486 TI - High frequency of cardiovascular risk factors in overweight adult Japanese subjects. AB - BACKGROUND: It has been suggested that Japanese subjects categorized as having normal weight (body mass index [BMI]<25.0) as defined by WHO (2000) have a tendency toward increased incidence of dyslipidemia and diabetes. Our objective was to assess the suitability for Japanese subjects of the Regional Office for the Western Pacific Region of WHO criteria pertaining to obesity (WPRO criteria, 2000) by analyzing cardiovascular risk factors relative to gender and age in overweight Japanese with BMI of 23.0-24.9. METHODS: There were 3,608 subjects (2,387 men: 42.3+/-0.2 years and 1,221 women: 41.6+/-0.3 years) who participated in a community setting and cross-sectional study and were not using any prescription drugs for obesity-related diseases. BMI and cardiovascular risk factors (blood pressure, plasma levels of total cholesterol, LDL-cholesterol, HDL cholesterol, triglyceride, Lp(a), glucose, HbA1C, uric acid, white blood cell count, AST, ALT and gamma-GTP) were compared by BMI classes and by gender and age group. RESULTS: The subjects were categorized as 21% "overweight" (23.0-24.9 BMI), 17% "obese I" (25.0-29.9 BMI) and 2% "obese II" (over 30.0 BMI), all based on WPRO criteria. Graded increases in BMI classes based on these WPRO criteria were positively associated with frequency and values of cardiovascular risk factors, and the "overweight" had a significantly higher risk of cardiovascular disease than did the "normal" subjects. CONCLUSION: While a relationship between BMI and cardiovascular risk factors is gender and age specific, our investigation, highlighting the increasing risks of "overweight" with a BMI of 23.0-24.9, suggests that WPRO criteria are more relevant and therefore suitable for Japanese subjects. PMID- 17350487 TI - Sequence analysis of mitochondrial DNA hypervariable regions: an approach to personal identification. AB - BACKGROUND: Mitochondrial DNA (mtDNA) sequence analysis of the hypervariable control region has been shown to be an effective tool for personal identification. The high copy and maternal mode of inheritance make mtDNA analysis particularly useful when old samples or degradation of biological samples prohibits the detection of nuclear DNA analysis. METHODS: This study reports mtDNA polymorphisms in both HV1 and HV2 of the non-coding D-loop region from 30 Iranian persons (10 unrelated families in three sequential maternal generations). RESULTS: Eighty one polymorphic nucleotide positions were found, 32 in HV1 and 49 in HV2. The sequence of HV1 and HV2 and the occurred polymorphism were completely similar in each family, except for heteroplasmy in five positions in HV2. The average numbers of nucleotide differences between families were 5.2 nucleotides in HV1 and 2.8 nucleotides in HV2. CONCLUSIONS: We expect eight nucleotide differences in sequence of both HV1 and HV2 in two unknown, unrelated Iranian samples. PMID- 17350488 TI - Can submaximal exercise variables predict peak exercise performance in women with chronic fatigue syndrome? AB - This study aimed at examining whether physiological exercise variables at the submaximal level, defined as 75% of the age-predicted target heart rate, are able to predict peak exercise performance in women with chronic fatigue syndrome (CFS) (n=222). Subjects performed a bicycle ergometric test against a graded increase in workload until exhaustion with continuous monitoring of electrocardiographic and ventilatory variables. Oxygen uptake at the submaximal level (VO2SUBMAX) correlated strongly with peak oxygen uptake (VO2PEAK) (r=0.70). For the prediction of VO2PEAK, linear regression analysis determined the line of best fit as: VO2PEAK=0.95xVO2SUBMAX+372.3. Using this equation, the mean error in the prediction was 14.6+/-11.2% (range 0.1-63.7%). It is concluded that the prediction of VO2PEAK based on VO2SUBMAX might be useful for analyzing group differences or treatment effects but not for individual (clinical) purposes. PMID- 17350489 TI - Prescription rheumatology practices among Mexican specialists. AB - BACKGROUND: We undertook this study to describe prescription practices and the degree of disease control in a large sample of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) treated by rheumatologists in Mexico. METHODS: Board-certified Mexican rheumatologists across the country were asked to assess consecutive RA and AS patients; 1208 patients completed a self administered questionnaire with information on demographics, disease duration, co morbidity, treatment, pain, disability and a validated Spanish version of instruments to measure physical function and quality of life. RESULTS: Of the 1096 RA patients, 88.1% were treated with nonsteroidal anti-inflammatory drugs (NSAIDs), 1020 (93.3%) with disease-modifying anti-rheumatic drugs (DMARDs), 365 (33.4%) with steroids, and 70 (6.4%) with biological agents. Their mean Health Assessment Questionnaire Disability Index (HAQ-Di) score was 1.21+/-0.80, Disease Activity Index, 28 joint count (DAS 28) 3.9+/-1.29, and Rheumatoid Arthritis Disease Activity Index (RADAI), 3.94+/-2.01. Regarding the 112 AS patients, 110 (98.2%) received NSAIDs, 90 (80.4%) were on DMARDs, 11 (9.8%) took steroids, and 11 (9.8%) received biological agents, their functional status shown as Bath Ankylosing Spondylitis Functional Index (BASFI) score of 4.4+/-2.5. Among the 1110 DMARD users, only 64 received one drug, and a great proportion used two or more DMARDs; 81 subjects (16.2%) were on biological agents, in any combination. RA patients more commonly used methotrexate, 791 (72%) cases, and hydroxychloroquine. Taking into account their diagnosis, the combination most prescribed was NSAIDs plus DMARDs in 660 subjects (54.7%). CONCLUSIONS: DMARDs in combination with other drug are the most frequently prescribed therapeutic scheme for RA and AS patients. These schemes used for both conditions by Mexican rheumatologists are in line with current international recommendations. PMID- 17350490 TI - Apolipoprotein B (APOB) gene polymorphism in patients with gallbladder disease. AB - Cholelithiasis is one of the most prevalent gastroenterological diseases, precipitated mainly by environmental factors. However, twin studies provided strong evidence for a role of genetic factors in the disease pathogenesis. An association between plasma lipoprotein levels and gallstone disease (GSD) was presented. Apolipoprotein B is an essential structural component of triglyceride rich lipoprotein particles and plays an important role in the maintenance of cholesterol homeostasis in mammals. Various studies have shown a relationship between APOB gene polymorphisms and lipoprotein levels, but only few investigated a potential association between APOB polymorphism and GSD, giving contrary results. In the current study, an association between common polymorphisms in APOB gene (T2488T and E4154K) and cholesterol gallstone disease was examined. Two hundred and forty patients of Caucasian origin suffering from cholelithiasis, as well as 217 healthy individuals, were included in the study. Patients were genotyped for two single nucleotide polymorphisms (SNPs) in APOB gene: 2488C>T (XbaI), and 4154G>A (EcoRI) using PCR-RLFP method. The resulting analysis has shown that polymorphic loci in positions 2488 and 4154 in APOB gene are in full linkage in a Polish population and form only three haplotypes: 2488C-4154G, 2488T 4154G and 2488C-4154A. Frequency and distribution of 2488C>T alleles did not differ significantly between patients and controls. The 4154G allele has been found to be associated with GSD (p=0.001). A risk of gallstone formation was reduced in 4154AA homozygotes (OR=0.25, p=0.009) and heterozygous individuals (OR=0.63, p=0.03) as compared to 4154GG homozygotes. Additionally, 2488C-4154A haplotype was identified as a protective factor against GSD (p=0.04). Our results suggest that SNPs in APOB, potentially considered as one of lith genes as well as certain haplotypes, may be risk factors for GSD. PMID- 17350491 TI - Follow-up study of patients diagnosed with chronic myelogenous leukemia treated with STI 571 in Ecuador. PMID- 17350493 TI - Tropical dermatology: Part II. PMID- 17350492 TI - Fifth International Symposium on Pneumococci and Pneumococcal Diseases, Alice Springs, Central Australia, 2-6 April 2006. PMID- 17350494 TI - Tungiasis and myiasis. AB - Tungiasis and myiasis are common ectoparasitic infestations that occur in developing countries in the tropics, particularly where poverty and poor standards of basic hygiene exist. The growth in international travel to and from these regions has led to an increase in the presentation of these conditions in nonendemic countries. Despite recent progress in the treatment and prevention of tungiasis and myiasis, diagnosis can present a challenge to those unfamiliar with these conditions, especially when they present in nonendemic countries. Tungiasis is caused by the penetration of the female sand flea, Tunga penetrans, into the epidermis of the host. Myiasis is a parasitic infection of the skin and mucous membranes in which the larvae of Diptera insects penetrate healthy or altered skin depending on the species. Infestations are usually self-limited and present few complications. Social neglect and inadequate health behavior in economically depressed urban neighborhoods, however, may lead to secondary infections and complications. PMID- 17350495 TI - Leprosy. AB - Leprosy is a granulomatous disease affecting the skin and nerves caused by Mycobacterium leprae. It continues to be a significant public health problem. Despite multidrug therapy, immunologic reactions continue to occur, leading to disability and deformity due to neuropathy. It is important that dermatologists are aware of the neurologic as well as the skin manifestations of the condition so that nerve involvement can be identified and treated rapidly. PMID- 17350496 TI - Cutaneous tuberculosis. AB - Cutaneous tuberculosis continues to be one of the most elusive and more difficult diagnoses to make for dermatologists practicing in developing countries. Not only because they have to consider a wider differential diagnosis (leishmaniasis, leprosy, actinomycosis, deep fungal infections, etc) but also because of the difficulty in obtaining a microbiological confirmation. Despite all the advances in microbiology, including sophisticated techniques such as polymerase chain reaction, the sensitivity of new methods are no better than the gold standard, that is, the isolation of Mycobacterium tuberculosum in culture. Even now, in the 21st century, we rely on methods as old as the intradermal reaction purified protein derivative (PPD) standard test and therapeutic trials, as diagnostic tools. In this situation, it is important to recognize the many clinical faces of cutaneous tuberculosis to prevent missed or delayed diagnoses. PMID- 17350497 TI - Sporotrichosis. AB - Sporotrichosis is a deep fungal disease caused by a dimorphic fungus, Sporothrix schenckii. It occurs more frequently in the tropical and subtropical areas and is mainly characterized by nodular lesions of cutaneous and subcutaneous tissues and adjacent lymphatics that suppurate and ulcerate. Infection occurs by manipulation of contaminated soil, cats, or some wild animals or by inhalation of spores. Itraconazole is the best drug for treatment of sporotrichosis. PMID- 17350498 TI - Chromoblastomycosis. AB - Chromoblastomycosis is a chronic subcutaneous mycotic infection caused by pigmented or dematiaceous saprophytic moulds ubiquitous in the environment. The most common etiologic agents are Fonsecaea pedrosoi and Cladophialophora carrionii, both of which can be isolated from plant debris. The infection usually follows traumatic inoculation through penetrating thorn or splinter wounds. The fungal agents develop as small clusters of cells known as muriform bodies. Several months after the injury, painless papules or nodules appear in the affected area progressing to scaly and verrucose plaques. Direct examinations of skin scrapings or histopathologic study demonstrates the typical muriform bodies. Microbiologic culture is necessary for the correct determination of the etiologic agent. Itraconazole is the treatment of choice, often in combination with surgery. Even so, results are often unsatisfactory as patients present late to medical services because of lack of funds and the fact that the disease usually affects the main family earner. PMID- 17350499 TI - Mycetoma. AB - Mycetoma is a granulomatous infection affecting mainly the feet and lower extremities. It can be caused either by aerobic, branched actinomycetes or by eumycetes. Most cases are found in tropical and subtropical regions. The infection is usually produced by the introduction of the etiologic agents through minor wounds caused by thorns and wood splinters. Clinically the disease begins as small, firm nodules that can enlarge to form extensive lesions with fistulae and abscesses with pus containing granules of the causative microorganisms. Antimicrobials and surgery are used in the management of mycetoma. The actinomycetomas generally respond well to antimicrobials. For eumycetomas, surgery may be required. New therapeutic options for drug-resistant cases are discussed. PMID- 17350500 TI - Cutaneous leishmaniasis. AB - Cutaneous leishmaniasis is a widespread tropical infection caused by numerous different species of Leishmania protozoa that are transmitted by sandflies. Its clinical presentations are extremely diverse and dependent on a variety of parasite and host factors that are poorly understood. Diagnosis should aim to identify the exact species involved, but this requires laboratory investigations that are not widely available. No single ideal treatment has been identified, and those available are limited by variable success rates and toxicity. Clinical guidelines are needed to make better use of the investigations and treatments that do exist. Prevention is currently limited to bite prevention measures. PMID- 17350502 TI - Skin care products and subtle data manipulation. AB - The dermatologists of today need to master the skills to help their patients in choosing skin care products. As physicians and scientists, we are naturally inclined to trust sophisticated and objectively derived data that are published in scientific, peer-reviewed journals and are presented to us in the form of numbers, tables, and graphs. The question that should be asked is whether a product that scored well in sophisticated tests is really superior and more suitable to the needs of our patients? Or, how far can we trust the data in scientific publications? There is no generally accepted methodology for unbiased evaluation of the efficacy and performance of skin care products. There is also no consensus on which test method best reflects the real-life performance of these products. And, most importantly, even the most objective methods and measuring devices can be and often are manipulated to support the claims of superiority of given products. We will show several out of many, many ways of how the study design, protocols, techniques, and end points can legitimately be adapted to the special characteristics of the specific product, emphasizing its advantages. PMID- 17350501 TI - Viral exanthems in the tropics. AB - Viral exanthems are a common problem in tropical regions, particularly affecting children. Most exanthems are transient and harmless, but some are potentially very dangerous. Pregnant women and malnourished or immunocompromised infants carry the greatest risk of adverse outcome. In this article, parvovirus B19; dengue and yellow fever; West Nile, Barmah Forest, Marburg, and Ebola viruses, and human herpesviruses; asymmetric periflexural exanthema of childhood; measles; rubella; enteroviruses; Lassa fever; and South American hemorrhagic fevers will be discussed. PMID- 17350503 TI - The joy of learning, practicing, and teaching dermatology--I did it my way! PMID- 17350504 TI - Patient education and counseling in a changing era of health care. PMID- 17350507 TI - Osteotomy for salvage of the arthritic ankle. AB - Ankle arthrodesis continues to be the procedure of choice for ankle arthritis. Coester and colleagues showed that arthrodesis is a significant risk factor for development of arthritis in the ipsilateral hindfoot and forefoot, however. Total ankle arthroplasty has gained significant interest but is not yet ideally suited for younger active patients because of unacceptable failure rates and complications. Osteotomies can play an important role in re-establishing normal alignment and potentially decreasing the rate of progression of wear on the articular surfaces and decreasing pain, which may allow more time before arthrodesis or arthroplasty are needed. The success of total ankle arthroplasty depends largely on the alignment of the foot and ankle and osteotomies can be used in a staged manner as part of a reconstructive effort including total ankle arthroplasty. Supramalleolar osteotomies can be used to align the tibia; alternatively, osteotomies in the midfoot and hindfoot can be used to balance the foot and ankle making them suitable for arthroplasty in an individual who perhaps would not otherwise have that treatment option. Further studies will continue to clarify the role and indications for osteotomies for treatment of ankle arthritis. PMID- 17350508 TI - The valgus ankle. AB - When a deformity of the hindfoot advances to the point where it begins to affect the alignment of the ankle, it becomes a particularly challenging problem to correct. Nonoperative options are limited and should be reserved for patients who have comorbidities prohibiting surgical attention. The associated deformities must first be corrected to protect the ankle realignment procedure. The goals of treatment are to maximise flexibility and produce a painless and plantigrade foot without the need for supplementary bracing. PMID- 17350509 TI - Distraction arthroplasty. AB - Few joint-preserving surgical options exist for the patient who has ankle arthritis refractory to conservative measures. Therefore, continuous effort is afforded to the development of additional treatment options for such patients. Distraction arthroplasty has been proposed as one of these options for the patient in whom fusion or joint replacement is not appropriate. Although the mechanism of action remains unknown, the reports of several researchers support the potential beneficial effects that can be obtained from joint distraction arthroplasty in the severely osteoarthritic ankle. Furthermore, the studies published to date suggest that these effects may not only persist for years but also improve as time progresses during the first several years after treatment. Although additional laboratory studies are needed to understand the biochemical and biomechanical effects of distraction, additional prospective clinical studies are also needed to further understand its efficacy and appropriate patient population. The data thus far suggests that joint distraction arthroplasty may be a viable alternative treatment to arthrodesis and replacement for the young patient who has a congruent, painful, mobile, arthritic ankle joint. PMID- 17350510 TI - Classification and treatment of severe ankle articular segment deficits: osteochondral allograft reconstruction. AB - Severe ankle degeneration can be a devastating problem for young adults. Although ankle fusion continues to be the gold standard, inherent long-term problems are related to this treatment option. Further advances in total ankle prosthetic arthroplasty are needed before this treatment option can be considered suitable in a younger population. The use of fresh osteochondral allograft transplantation can provide an alternative treatment option without precluding future salvage procedures. Future studies may further define the role immunosuppression can play in improving fresh osteochondral allograft viability. PMID- 17350511 TI - Combined subtalar and ankle arthritis. AB - Combined ankle and subtalar arthritis is a difficult problem for which there are varied solutions. Each solution has its advantages and disadvantages. Treatment must be specifically tailored to the patient's needs, comorbidities, and expectations. Because of the complicated nature of this condition and its treatment, complications are common and should be anticipated. PMID- 17350512 TI - Bioadjuvants for complex ankle and hindfoot reconstruction. AB - Many reconstructive options exist for symptomatic hindfoot and ankle problems. Hindfoot and tibiotalar fusions are reliable procedures with consistent results. Unfortunately, many potential complications have been cited throughout the literature. Although the most important aspect in any fusion surgery is meticulous technique, advances in technology, including PRP, bone stimulators, and BMPs seem to be useful additions in the quest to achieve solid fusions with decreased complications. PMID- 17350513 TI - Soft tissue complications following calcaneal fractures. AB - Soft tissue complications following calcaneal fractures can be frustrating to the patient and present reconstructive challenges for the surgeon. Preoperative patient assessment may define a group of patients who are best treated nonoperatively in an effort to avoid disastrous soft tissue complications. Late sequelae will continue to be seen and through the use of differential injections, physical exam, and appropriate intervention, the practitioner can usually decrease symptoms and improve a patient's function. Further studies in the treatment of open calcaneal fractures are necessary to better define treatment algorithms. A working knowledge of these complications and their management is necessary for the surgeon treating calcaneal fractures. PMID- 17350514 TI - Calcaneus malunion and nonunion. AB - Though the debate continues between operative interventions versus conservative therapy, there is significant evidence that the deformity that results from calcaneus malunions causes significant disability for the patient. Knowledge of the fracture patterns in the original calcaneal fracture aids in both understanding the deformity of the malunion and the necessary steps for correction of the deformity. Increased heel width, subfibular impingement, tibiotalar impingement, varus/valgus deformity of the hindfoot, peroneal tendon dysfunction, and subtalar arthrosis are well established consequences of calcaneal malunion. Different surgical options have been postulated either trying to address all the deformities or concentrating on certain aspects that are most clinically pressing. The simplest form of treatment is isolated lateral wall decompression, and if applied to a patient who has minimal subtalar arthrosis and no hindfoot deformity, good results are produced. The more complex surgical interventions aim to correct the lateral ankle symptoms, subtalar arthrosis, and hindfoot varus. These surgeries result in a more functional foot but should be considered a salvage procedure because there is still considerable disability as indicated by lower functional scores on the Short Form 36 and American Orthopaedic Foot and Ankle Society hindfoot surveys. Nonunion in calcaneal fractures has limited incidence within the literature for both operative and nonoperative management. Thus, any conclusion as to why there would be such a low incidence can only be made on speculation that the vascularity of the calcaneus and ability to immobilize both the subtalar and calcaneocuboid joints allow the fracture to heal. PMID- 17350515 TI - Post talus neck fracture reconstruction. AB - Talar neck fractures are interesting fractures that require careful ORIF if the patient factors allow. The long-term sequelae of these fractures can be severe regardless of the quality of the reconstruction. Posttraumatic arthritis and avascular necrosis are devastating complications that are unfortunately common. Malunion and nonunion of talar neck fractures need to be evaluated carefully with attention to adjacent joints. A full workup is needed to fully evaluate the patient and fracture factors. If the patient has failed nonoperative treatment then reconstruction or salvage is considered. Reconstruction of ununited and malunited talar neck fractures can be successful if the patient is well selected. Corrective fusion is a viable alternative for those patients who have posttraumatic arthritis. Combined ankle replacement and subtalar fusion remains another motion-conserving procedure. PMID- 17350516 TI - Reconstruction of the varus ankle from soft-tissue procedures with osteotomy through arthrodesis. AB - Cavovarus foot and ankle reconstruction is done to preserve motion whenever possible, and to maintain or impart stability, realigning foot and ankle joints into as anatomic a position as possible to restore a more normal mechanical axis to the extremity, and redistribute joint pressure or load more evenly. In patients who have a flexible deformity based on the Coleman block test, this is accomplished through calcaneal and metatarsal osteotomies to preserve joint motion, even in the presence of osteoarthritis. In cases of rigid and nonreducible deformity, the rigid cavovarus foot and ankle are addressed using a modified triple arthrodesis, an ankle arthrodesis, a tibiotalocalcaneal arthrodesis, or pantalar arthrodesis. In most patients, bony procedures are combined with soft-tissue realignment procedures. PMID- 17350517 TI - Ankle instability and impingement. AB - Ankle instability and ankle impingement are well-known complications of an ankle sprain. Both diagnosis are made primarily by history and physical examination. Ankle instability may resolve with physical therapy, but can require surgical reconstruction. Anatomic reconstruction is preferred whenever possible. Ankle impingement usually requires surgical treatment. Anterior soft tissue impingement and mild bony impingement confined to the tibia can be treated arthroscopically, whereas more severe anterior bony impingement and any form of posterior impingement require an open procedure. Ankle ligament reconstruction and surgical treatment of ankle impingement are reliably effective procedures. PMID- 17350519 TI - Prepuncture ultrasound-measured distance: an accurate reflection of epidural depth in infants and small children. AB - BACKGROUND AND OBJECTIVES: Epidural cannulation is technically difficult in children who have small anatomic structures. Ultrasound information regarding the distance of skin-to-ligament flavum may be useful, leading to an increase in success rate without dural puncture. This study was performed to assess whether ultrasound-measured, skin-to-ligament flavum distance would reflect the needle depth during epidural puncture in infants and children. METHODS: The study compromised 180 children, aged 2 to 84 months, undergoing urologic surgery. After induction of anesthesia, ultrasound images of the longitudinal median and transverse views were acquired from L4-L5 in lateral decubitus position. Measured distance of skin-to-ligament flavum in each view was compared with the perpendicular skin-to-epidural depth, which was obtained from needle depth and angle by use of a trigonometric ratio equation. Additionally, we evaluated the ultrasound visibility of the ligament flavum and dura mater, number of puncture attempts, and complications. RESULTS: The correlation coefficient between measured distance and perpendicular epidural depth was slightly higher in longitudinal median view (R2 = 0.848) than in transverse view (R2 = 0.788). The visibility of ligament flavum and dura mater was "good" in 91 and 170 of 180 patients, respectively, and "sufficient" in the remaining subjects. The epidural space was located on first puncture attempt in 179 of 180 cases (99.4%). No incidents of dural puncture or bloody tap occurred. CONCLUSIONS: Ultrasound, particularly in the longitudinal median view, provides accurate information on the distance of skin-to-ligament flavum in infants and children. With reference to the measured distance, epidural puncture can be performed with minimal risk of dural puncture (upper limit of 95% CI = 1.67%). PMID- 17350518 TI - Comparison of 0.25% levobupivacaine, 0.25% bupivacaine, and 0.125% bupivacaine for duration and magnitude of action in peripheral arterial blood flow induced by sympathetic block in dogs. AB - BACKGROUND AND OBJECTIVES: The aim of this study is to compare 0.25% levobupivacaine with 0.25% bupivacaine and 0.125% bupivacaine to examine the duration and magnitude of vasodilative effect induced by sympathetic block. METHODS: We measured mean arterial pressure (MAP), heart rate (HR), and right and left brachial-artery blood flow (BABF) before and after cervicothoracic sympathetic block in 24 dogs. The experimental protocol was designed as follows: (1) left cervicothoracic sympathetic block with 1.0 mL of 0.25% levobupivacaine (n = 8), (2) left cervicothoracic sympathetic block with 1.0 mL of 0.25% bupivacaine (n = 8), and (3) left cervicothoracic sympathetic block with 1.0 mL of 0.125% bupivacaine (n = 8). RESULTS: MAP and HR did not change significantly throughout the study in either group. Left cervicothoracic sympathetic block with 0.25% levobupivacaine increased left BABF significantly from 5 minutes through 80 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 185 +/- 35%; P <.01). Left cervicothoracic sympathetic block with 0.25% bupivacaine increased left BABF significantly from 5 minutes through 100 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 251 +/- 47%; P < .01). Left cervicothoracic sympathetic block with 0.125% bupivacaine increased left BABF significantly from 5 minutes through 80 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 155 +/- 20%; P < .01). CONCLUSIONS: 0.25% Levobupivacaine may have a lower potency compared with 0.25% bupivacaine in sympathetic block in dogs. PMID- 17350520 TI - Characterizing novice behavior associated with learning ultrasound-guided peripheral regional anesthesia. AB - BACKGROUND AND OBJECTIVES: Ultrasound-guided regional anesthesia is a rapidly growing field. There exists little information regarding the competencies involved with such a practice. The objective of this exploratory study was to characterize the behavior of novices as they undertook the challenges of learning a new technique. In addition to assessing for both committed errors and accuracy, we aimed to identify previously unrecognized quality-compromising behaviors that could help structure effective training interventions. METHODS: By using detailed video analyses, the performances of 6 anesthesia residents were evaluated while on a dedicated 1-month rotation in ultrasound-guided regional anesthesia. From these video reviews, we assessed accuracy, errors committed, performance times, and searched for previously unrecognized quality-compromising behaviors. RESULTS: A total of 520 nerve blocks were videotaped and reviewed. All residents performed at least 66 nerve blocks, with an overall success rate of 93.6% and 4 complications. Both speed and accuracy improved throughout the rotation. There were a total of 398 errors committed, with the 2 most common errors consisting of the failure to visualize the needle before advancement and unintentional probe movement. Five quality-compromising patterns of behavior were identified: (1) failure to recognize the maldistribution of local anesthesia, (2) failure to recognize an intramuscular location of the needle tip before injection, (3) fatigue, (4) failure to correctly correlate the sidedness of the patient with the sidedness of the ultrasound image, and (5) poor choice of needle-insertion site and angle with respect to the probe preventing accurate needle visualization. CONCLUSIONS: Based on the analysis of the committed errors and the identification of quality-compromising behaviors, we are able to recommend important targets for learning in future training and simulation programs. PMID- 17350521 TI - Demonstration of the spread of injectate with deep cervical plexus block: a case series. AB - BACKGROUND AND OBJECTIVES: The authors conducted a scanographic study in order to characterize the local anesthetic spread of injectate resulting from a single injection technique of deep cervical plexus block. METHODS: Six consecutive American Society of Anesthesiologists II and III patients scheduled for elective carotid endarterectomy under regional anesthesia were enrolled. Deep cervical plexus block was placed via an anterolateral approach using a nerve stimulator to guide the injection on contact with the levator scapulae nerve. With specific contractions evoked at a stimulating current intensity or = 4 drugs) (odds ratio [OR]=10.3; 95% confidence interval [CI]=3.8-27.8); IPDs (OR=8.4; 95% CI=2.7-25.5); and having a heart condition (OR=6.0; 95% CI=1.6 22.8). The logistic model yielded one predictor for PDDIs in Florida: polypharmacy (> or = 4 drugs) (OR=9.7; 95% CI=1.4-65.4). The 3-year RR for PDDIs (New York) was 1.8 (95% CI=1.2-2.8) from polypharmacy and 2.1 (95% CI=1.3-3.3) from IPDs. CONCLUSIONS: Although this research is exploratory and used a small convenience sample, the estimates obtained suggest consideration of prospective hypothesis testing using a larger database and a greater number of subjects using more recent medications. Prospective examination of developing drug-drug interactions in this way will enhance the generalizability of these findings. This study shows similarities in the prevalence rates between 2 historical cohorts in 2 states, thereby suggesting plausibility of findings. PMID- 17350561 TI - A study of the additional costs of dispensing workers' compensation prescriptions. AB - BACKGROUND: Although there is a significant amount of additional work involved in dispensing workers' compensation prescriptions, these costs have not been quantified. A study of the additional costs to dispense a workers' compensation prescription is needed to measure actual costs and to help determine the reasonableness of reimbursement for prescriptions dispensed under workers' compensation programs. OBJECTIVES: The purpose of this study was to determine the minimum additional time and costs required to dispense workers' compensation prescriptions in Texas. METHODS: A convenience sample of 30 store-level pharmacy staff members involved in submitting and processing prescription claims for the Texas Mutual workers' compensation program were interviewed by telephone. Data collected to determine the additional costs of dispensing a workers' compensation prescription included (1) the amount of additional time and personnel costs required to dispense and process an average workers' compensation prescription claim, (2) the difference in time required for a new versus a refilled prescription, (3) overhead costs for processing workers' compensation prescription claims by experienced experts at a central processing facility, (4) carrying costs for workers' compensation accounts receivable, and (5) bad debts due to uncollectible workers' compensation claims. RESULTS: The median of the sample pharmacies' additional costs for dispensing a workers' compensation prescription was estimated to be at least $9.86 greater than for a cash prescription. CONCLUSIONS: This study shows that the estimated costs for workers' compensation prescriptions were significantly higher than for cash prescriptions. These costs are probably much more than most employers, workers' compensation payers, and pharmacy managers would expect. It is recommended that pharmacy managers should estimate their own costs and compare these costs to actual reimbursement when considering the reasonableness of workers' compensation prescriptions and whether to accept these prescriptions. PMID- 17350562 TI - Innovation and the WHO's essential medicines list: giving credit where credit is due. PMID- 17350563 TI - Indian pharma enters the global arena. AB - Although known as a major supplier of generic drugs, India has begun to forge new alliances with big US and European pharma companies. Such collaborations are helping to shepherd Indian drug companies into a new era of innovative drug discovery, but regulations governing patents, drug approvals, and clinical trials are still in the process of being updated. PMID- 17350564 TI - Establishing the triplet nature of the genetic code. AB - In 1961, Crick, Barnett, Brenner, and Watts-Tobin (Crick et al., 1961) designed an elegant experimental strategy to determine the nature of the genetic code. Remarkably, they reached the correct conclusion despite the absence of technology to analyze and compare DNA and protein sequences. PMID- 17350565 TI - Nuclear actions in innate immune signaling. AB - Innate immunity in plants and animals is mediated through pattern recognition receptors, which were thought to initiate signaling in the cytoplasm to activate defense pathways. Shen et al. (2006) and Burch-Smith et al. (2007) now provide compelling evidence that certain plant disease resistance proteins, which detect specific pathogenic effectors, act in the nucleus to trigger downstream signaling and defense pathways. PMID- 17350566 TI - Magic spots cast a spell on DNA primase. AB - The bacterial signaling molecules ppGpp and pppGpp regulate transcription initiation in response to starvation by altering RNA polymerase activity. In this issue, Wang et al. (2007) show that (p)ppGpp also inhibits DNA replication elongation by interfering with DNA primase activity. Halting replication may help cells to maintain genomic integrity during periods of transient nutrient limitation. PMID- 17350567 TI - From stem cell to progenitor and back again. AB - Under normal homeostatic conditions, tissue stem cells undergo long-term self renewal and produce progeny that differentiate into several different cell types. But what happens if the stem cells are lost? In a recent issue of Developmental Cell, Nakagawa et al. (2007) propose that the progeny of stem cells, called transit-amplifying progenitor cells, are able to replace lost stem cells. PMID- 17350568 TI - The sunny side of p53. AB - Skin, the largest organ of our body, is often plagued by cancer because of exposure to ultraviolet radiation from the sun. A report by Cui et al. (2007) in this issue of Cell explains how the tumor suppressor p53 protects the skin by stimulating the suntan response. PMID- 17350569 TI - N-WASP generates a buzz at membranes on the move. AB - The fast-growing ends of actin filaments push against membranes to create cell surface protrusions and to propel the movement of membrane vesicles. Co et al. (2007) now show that the neural Wiskott-Aldrich syndrome protein (N-WASP) mediates dynamic attachment between membranes and the growing ends of actin filaments to sustain membrane movement. PMID- 17350570 TI - Autophagy: paying Charon's toll. AB - Autophagy (literally self-eating) has diverse cytoprotective functions but also is linked to programmed cell death (PCD). In this issue, Qu et al. (2007) analyze the role of autophagy in PCD during development. Unexpectedly they find that autophagy induces apoptotic cells to present a signal to ensure their clearance, which is crucial for mouse embryonic morphogenesis. PMID- 17350571 TI - Wild-type p53: tumors can't stand it. AB - Most malignant tumors disrupt the p53 signaling pathway in order to grow and survive. Although many genes in addition to p53 are mutated in tumors, recent studies by Ventura et al. (2007) and Xue et al. (2007) suggest that restoring p53 function alone is sufficient to cause regression of several different tumor types in mice and thus might represent a potent therapeutic strategy to treat certain human cancers. Martins et al. (2006) also demonstrate that restoration of p53 activity results in tumor regression but add the sobering caveat that tumors may be able to quickly generate resistance by finding other ways to disrupt the p53 pathway. PMID- 17350572 TI - Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. AB - ALIX/AIP1 functions in enveloped virus budding, endosomal protein sorting, and many other cellular processes. Retroviruses, including HIV-1, SIV, and EIAV, bind and recruit ALIX through YPX(n)L late-domain motifs (X = any residue; n = 1-3). Crystal structures reveal that human ALIX is composed of an N-terminal Bro1 domain and a central domain that is composed of two extended three-helix bundles that form elongated arms that fold back into a "V." The structures also reveal conformational flexibility in the arms that suggests that the V domain may act as a flexible hinge in response to ligand binding. YPX(n)L late domains bind in a conserved hydrophobic pocket on the second arm near the apex of the V, whereas CHMP4/ESCRT-III proteins bind a conserved hydrophobic patch on the Bro1 domain, and both interactions are required for virus budding. ALIX therefore serves as a flexible, extended scaffold that connects retroviral Gag proteins to ESCRT-III and other cellular-budding machinery. PMID- 17350573 TI - Central role of p53 in the suntan response and pathologic hyperpigmentation. AB - UV-induced pigmentation (suntanning) requires induction of alpha-melanocyte stimulating hormone (alpha-MSH) secretion by keratinocytes. alpha-MSH and other bioactive peptides are cleavage products of pro-opiomelanocortin (POMC). Here we provide biochemical and genetic evidence demonstrating that UV induction of POMC/MSH in skin is directly controlled by p53. Whereas p53 potently stimulates the POMC promoter in response to UV, the absence of p53, as in knockout mice, is associated with absence of the UV-tanning response. The same pathway produces beta-endorphin, another POMC derivative, which potentially contributes to sun seeking behaviors. Furthermore, several instances of UV-independent pathologic pigmentation are shown to involve p53 "mimicking" the tanning response. p53 thus functions as a sensor/effector for UV pigmentation, which is a nearly constant environmental exposure. Moreover, this pathway is activated in numerous conditions of pathologic pigmentation and thus mimics the tanning response. PMID- 17350574 TI - Nutritional control of elongation of DNA replication by (p)ppGpp. AB - DNA replication is highly regulated in most organisms. Although much research has focused on mechanisms that regulate initiation of replication, mechanisms that regulate elongation of replication are less well understood. We characterized a mechanism that regulates replication elongation in the bacterium Bacillus subtilis. Replication elongation was inhibited within minutes after amino acid starvation, regardless of where the replication forks were located on the chromosome. We found that small nucleotides ppGpp and pppGpp, which are induced upon starvation, appeared to inhibit replication directly by inhibiting primase, an essential component of the replication machinery. The replication forks arrested with (p)ppGpp did not recruit the recombination protein RecA, indicating that the forks are not disrupted. (p)ppGpp appear to be part of a surveillance mechanism that links nutrient availability to replication by rapidly inhibiting replication in starved cells, thereby preventing replication-fork disruption. This control may be important for cells to maintain genomic integrity. PMID- 17350575 TI - Mechanism of actin network attachment to moving membranes: barbed end capture by N-WASP WH2 domains. AB - Actin filament networks exert protrusive and attachment forces on membranes and thereby drive membrane deformation and movement. Here, we show that N-WASP WH2 domains play a previously unanticipated role in vesicle movement by transiently attaching actin filament barbed ends to the membrane. To dissect the attachment mechanism, we reconstituted the propulsive motility of lipid-coated glass beads, using purified soluble proteins. N-WASP WH2 mutants assembled actin comet tails and initiated movement, but the comet tails catastrophically detached from the membrane. When presented on the surface of a lipid-coated bead, WH2 domains were sufficient to maintain comet tail attachment. In v-Src-transformed fibroblasts, N WASP WH2 mutants were severely defective in the formation of circular podosome arrays. In addition to creating an attachment force, interactions between WH2 domains and barbed ends may locally amplify signals for dendritic actin nucleation. PMID- 17350576 TI - Coronin 1B coordinates Arp2/3 complex and cofilin activities at the leading edge. AB - Actin filament formation and turnover within the treadmilling actin filament array at the leading edge of migrating cells are interdependent and coupled, but the mechanisms coordinating these two activities are not understood. We report that Coronin 1B interacts simultaneously with Arp2/3 complex and Slingshot (SSH1L) phosphatase, two regulators of actin filament formation and turnover, respectively. Coronin 1B inhibits filament nucleation by Arp2/3 complex and this inhibition is attenuated by phosphorylation of Coronin 1B at Serine 2, a site targeted by SSH1L. Coronin 1B also directs SSH1L to lamellipodia where SSH1L likely regulates Cofilin activity via dephosphorylation. Accordingly, depleting Coronin 1B increases phospho-Cofilin levels, and alters lamellipodial dynamics and actin filament architecture at the leading edge. We conclude that Coronin 1B's coordination of filament formation by Arp2/3 complex and filament turnover by Cofilin is required for effective lamellipodial protrusion and cell migration. PMID- 17350577 TI - Autophagy gene-dependent clearance of apoptotic cells during embryonic development. AB - Autophagy is commonly observed in metazoan organisms during programmed cell death (PCD), but its function in dying cells has been unclear. We studied the role of autophagy in embryonic cavitation, the earliest PCD process in mammalian development. Embryoid bodies (EBs) derived from cells lacking the autophagy genes, atg5 or beclin 1, fail to cavitate. This defect is due to persistence of cell corpses, rather than impairment of PCD. Dying cells in autophagy gene null EBs fail to express the "eat-me" signal, phosphatidylserine exposure, and secrete lower levels of the "come-get-me" signal, lysophosphatidylcholine. These defects are associated with low levels of cellular ATP and are reversed by treatment with the metabolic substrate, methylpyruvate. Moreover, mice lacking atg5 display a defect in apoptotic corpse engulfment during embryonic development. We conclude that autophagy contributes to dead-cell clearance during PCD by a mechanism that likely involves the generation of energy-dependent engulfment signals. PMID- 17350578 TI - An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. AB - During heart development the second heart field (SHF) provides progenitor cells for most cardiomyocytes and expresses the homeodomain factor Nkx2-5. We now show that feedback repression of Bmp2/Smad1 signaling by Nkx2-5 critically regulates SHF proliferation and outflow tract (OFT) morphology. In the cardiac fields of Nkx2-5 mutants, genes controlling cardiac specification (including Bmp2) and maintenance of the progenitor state were upregulated, leading initially to progenitor overspecification, but subsequently to failed SHF proliferation and OFT truncation. In Smad1 mutants, SHF proliferation and deployment to the OFT were increased, while Smad1 deletion in Nkx2-5 mutants rescued SHF proliferation and OFT development. In Nkx2-5 hypomorphic mice, which recapitulate human congenital heart disease (CHD), OFT anomalies were also rescued by Smad1 deletion. Our findings demonstrate that Nkx2-5 orchestrates the transition between periods of cardiac induction, progenitor proliferation, and OFT morphogenesis via a Smad1-dependent negative feedback loop, which may be a frequent molecular target in CHD. PMID- 17350579 TI - Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila. AB - Anaplastic lymphoma kinase (Alk) has been proposed to regulate neuronal development based on its expression pattern in vertebrates and invertebrates; however, its function in vivo is unknown. We demonstrate that Alk and its ligand Jelly belly (Jeb) play a central role as an anterograde signaling pathway mediating neuronal circuit assembly in the Drosophila visual system. Alk is expressed and required in target neurons in the optic lobe, whereas Jeb is primarily generated by photoreceptor axons and functions in the eye to control target selection of R1-R6 axons in the lamina and R8 axons in the medulla. Impaired Jeb/Alk function affects layer-specific expression of three cell adhesion molecules, Dumbfounded/Kirre, Roughest/IrreC, and Flamingo, in the medulla. Moreover, loss of flamingo in target neurons causes some R8-axon targeting errors observed in Jeb and Alk mosaic animals. Together, these findings suggest that Jeb/Alk signaling helps R-cell axons to shape their environment for target recognition. PMID- 17350580 TI - The XIST noncoding RNA functions independently of BRCA1 in X inactivation. AB - Females with germline mutations in BRCA1 are predisposed to develop breast and ovarian cancers. A previous report indicated that BRCA1 colocalizes with and is necessary for the correct localization of XIST, a noncoding RNA that coats the inactive X chromosome (Xi) to mediate formation of facultative heterochromatin. A model emerged from this study suggesting that loss of BRCA1 in female cells could reactivate genes on the Xi through loss of the XIST RNA. However, our independent studies of BRCA1 and XIST RNA revealed little evidence to support this model. We report that BRCA1 is not enriched on XIST RNA-coated chromatin of the Xi. Neither mutation nor depletion of BRCA1 causes significant changes in XIST RNA localization or X-linked gene expression. Together, these results do not support a role for BRCA1 in promoting XIST RNA localization to the Xi or regulating XIST dependent functions in maintaining the stability of facultative heterochromatin. PMID- 17350581 TI - Further evidence for BRCA1 communication with the inactive X chromosome. AB - BRCA1, a breast and ovarian cancer-suppressor gene, exerts tumor-suppressing functions that appear to be associated, at least in part, with its DNA repair, checkpoint, and mitotic regulatory activities. Earlier work from our laboratory also suggested an ability of BRCA1 to communicate with the inactive X chromosome (Xi) in female somatic cells (Ganesan et al., 2002). Xiao et al. (2007) (this issue of Cell) have challenged this conclusion. Here we discuss recently published data from our laboratory and others and present new results that, together, provide further support for a role of BRCA1 in the regulation of XIST concentration on Xi in somatic cells. PMID- 17350582 TI - The site-specific installation of methyl-lysine analogs into recombinant histones. AB - Histone lysine residues can be mono-, di-, or trimethylated. These posttranslational modifications regulate the affinity of effector proteins and may also impact chromatin structure independent of their role as adaptors. In order to study histone lysine methylation, particularly in the context of chromatin, we have developed a chemical approach to install analogs of methyl lysine into recombinant proteins. This approach allows for the rapid generation of large quantities of histones in which the site and degree of methylation can be specified. We demonstrate that these methyl-lysine analogs (MLAs) are functionally similar to their natural counterparts. These methylated histones were used to examine the influence of specific lysine methylation on the binding of effecter proteins and the rates of nucleosome remodeling. This simple method of introducing site-specific and degree-specific methylation into recombinant histones provides a powerful tool to investigate the biochemical mechanisms by which lysine methylation influences chromatin structure and function. PMID- 17350583 TI - SnapShot: actin regulators II. PMID- 17350584 TI - Novel fucogangliosides found in human colon adenocarcinoma tissues by means of glycomic analysis. AB - The structures of acidic glycosphingolipids in colon adenocarcinoma have been analyzed extensively using a number of conventional methods, such as thin-layer chromatography and methylation analysis, and a variety of acidic glycosphingolipids present in the tissues have been reported. However, because of a number of limitations in the techniques used in previous studies in terms of resolution, quantification, and sensitivity, we employed a different method that could be applied to small amounts of tissue. In this technique, the carbohydrate moieties of acidic glycosphingolipids from approximately 20mg of colon adenocarcinoma were released by endoglycoceramidase II and were labeled by pyridylamination. They were separated and structurally characterized by a two dimensional HPLC mapping technique, electrospray ionization tandem mass spectrometry (ESI-MS/MS), and enzymatic cleavage. A total of 22 major acidic glycosphingolipid structures were identified, and their relative quantities were revealed in detail. They are composed of 1 sulfated (SM3), 1 lacto-series (SLe(a)), 6 kinds of ganglio-series, and 14 kinds of neolacto-series glycosphingolipids. They include most of the acidic glycosphingolipids previously reported to be present in the tissues and two previously unknown fucogangliosides sharing the same terminal structure: NeuAcalpha2-6(Fucalpha1-2)Galbeta1 4GlcNAcbeta1-3Galbeta1-4Glc, and NeuAcalpha2-6(Fucalpha1-2)Galbeta1-4GlcNAcbeta1 3Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3-Galbeta1-4Glc. Thus, this highly sensitive, high-resolution analysis enabled the identification of novel structures of acidic glycosphingolipids from small amounts of already comprehensively studied cancerous tissues. This method is a powerful tool for microanalysis of glycosphingolipid structures from small quantities of cancerous tissues and should be applicable to different types of malignant tissues. PMID- 17350585 TI - Synthesis of hairpin probe using deoxyguanosine as a quencher: Fluorescence and hybridization studies. PMID- 17350586 TI - Roles of intrinsic and extrinsic tongue muscles in feeding: electromyographic study in pigs. AB - The performance of tongue muscles in various feeding behaviours is not well defined. This study was undertaken to examine the role of the intrinsic and extrinsic tongue muscles during natural drinking, food ingestion and chewing. Ten 12-week-old Yucatan miniature pigs (5 in each gender) were used. Under anesthesia, fine-wire electrodes were inserted into three intrinsic (verticalis and transversus [V/T]; superior and inferior longitudinalis [SL and IL]) and two extrinsic (genioglossus [GG] and styloglossus [SG]) tongue muscles and two jaw muscles (masseter [MA] and anterior digastricus [DI]). Electromyogram (EMG) and jaw movement were recorded and synchronized when pigs were drinking water, ingesting and chewing food freely. Chewing frequency (CF), onset of activation, burst duration and integrated activity (IEMG) were assessed quantitatively, and EMG activities during drinking and ingestion were examined qualitatively. Results indicate that during chewing, the V/T and GG had one phase of activity starting at early jaw opening, and the V/T activity lasted through late of jaw closing. The SL, IL and SG had double phases with the first starting at jaw opening and the second at late jaw closing phases. The three intrinsic tongue muscles and the SG were active during 35-48% of the chewing cycle. IEMG values of the SL, IL and SG of both sides were significantly greater compared to the other muscles (p<0.05 0.01). Both the SL and the IL showed significantly higher activities in the contralateral than ipsilateral sides (p<0.05). The timing sequences of both extrinsic and intrinsic muscles were similar between ingestion and chewing, but amplitudes of the GG and IL were greatly enhanced and those of the MA and SL were reduced during ingestion. The simultaneous activation of the MA, GG and V/T were seen during drinking, along with major activity in the GG and V/T. These results suggested that the majority of activity in the intrinsic and extrinsic tongue muscles occurred during jaw opening and the occlusal phases of chewing. The activity of the GG and IL played a major role during ingestion, whereas simultaneous activation of jaw, extrinsic and intrinsic tongue muscles and major activity in the GG and V/T occurred during drinking. PMID- 17350587 TI - Immortalization and characterization of human dental pulp cells with odontoblastic differentiation. AB - OBJECTIVE: To immortalize human dental pulp (HDP) cell showing stable growth and high mineralization activities in vitro. DESIGN: HDP cells were obtained from a healthy third molar and immortalized by transfection with human telomerase transcriptase (hTERT) gene. To examine the characters of hTERT transfected HDP (HDP-hTERT) cells, we examined expression of mRNA for dentin sialophosphoprotein (DSSP), type I collagen (COLI), alkaline phosphatase (ALP) and bone sialoprotein (BSP) by RT-PCR. In addition, we examined ALP activity by biochemical method and nodule formation by alizarin red S (ALZ) staining. RESULTS: HDP-hTERT was obtained by transfection with hTERT gene. These cells bypassed the senescence and grew over 120 population doublings (PDLs) without significant growth retardation. High expression of hTERT was confirmed in HDP-hTERT by RT-PCR and showed remarkable telomerase activity. Both HDP-original (HDP-ori) and HDP-hTERT expressed DSSP, COLI, ALP and BSP mRNA and showed ALP activity and ALZ staining at the same levels. CONCLUSIONS: We were able to establish a cell line of immortalized human dental pulp cells with odontoblastic differentiation which will be a useful cell model for studying the mechanism of proliferation and differentiation of odontoblasts. PMID- 17350588 TI - Exploring pathways and barriers for coupled ET/PT in cytochrome c oxidase: a general framework for examining energetics and mechanistic alternatives. AB - Gaining a detailed understanding of the energetics of the proton pumping process in cytochrome c oxidase (CcO) is one of the challenges of modern biophysics. Although there are several current mechanistic proposals, most of these ideas have not been subjected to consistent structure-function considerations. In particular most works have not related the activation barriers for different mechanistic proposals to the protein structure. The present work describes a general approach for exploring the energetics of different feasible models of the action of CcO, using the observed protein structure, established simulation methods and a modified Marcus' formulation. We start by reviewing our methods for evaluation of the energy diagrams for different proton translocation paths and then present a systematic analysis of various constraints that should be imposed on any energy diagram for the pumping process. After the general analysis we turn to the actual computational study, where we construct energy diagrams for forward and backward paths, using the estimated calculated reduction potentials and pK(a) values of all the relevant sites (including internal water molecules). We then explore the relationship between the calculated energy diagrams and key experimental constraints. This comparison allows us to identify some barriers that are not fully consistent with the overall requirement for an efficient pumping. In particular we identify back leakage channels, which are hard to block without stopping the forward channels. This helps to identify open problems that will require further experimental and theoretical studies. We also consider reasonable adjustments of the calculated barriers that may lead to a working pump. Although the present analysis does not establish a unique and workable model for the mechanism of CcO, it presents what is probably the most consistent current analysis of the barriers for different feasible pathways. Perhaps more importantly, the framework developed here should provide a general way for examining any proposal for the action of CcO as well as for the analysis of further experimental findings about the action of this fascinating system. PMID- 17350589 TI - Cultural mediators of self-reported social anxiety. AB - East Asians generally endorse higher social anxiety than do Westerners. Widely used measures of social anxiety, however, may not account for different social values across cultures. Drawing from Korean (n=251) and Euro-Canadian (n=250) community samples, this study used a cross-sectional design to examine the relationship between ratings of social anxiety and beliefs and self-views typically found in East Asian cultures. Results indicated that independent self construal and identity consistency, views of the self that are typically associated with Western cultures, fully mediate the ethnic difference on self reported social anxiety. Moreover, two indicators of East Asian views of the self in social contexts (interdependent self-construal and self-criticism) were partial mediators. Overall, the data suggest conceptualizations of pathological social anxiety may need to be revised to be useful for studying individuals in East Asian cultures. PMID- 17350590 TI - The flexible application of a manualized treatment for PTSD symptoms and functional impairment related to the 9/11 World Trade Center attack. AB - The purpose of this treatment effectiveness study was to evaluate the flexible application of a manualized cognitive behavioral treatment (CBT) for PTSD and related symptoms in survivors of the 9/11 terrorist attack on the World Trade Center. Treatment delivery ranged from 12 to 25 sessions; therapist experience ranged from no prior training to extensive training in CBT; and training and supervision of clinicians in the treatment manual was considerably less than that required in a randomized clinical trial (RCT). Paired t-tests demonstrated significant pre-post reductions in symptoms of PTSD and depression for the flexible application of the treatment. A benchmarking analysis revealed that the moderate-to-large effect sizes found for these variables were similar to those obtained in an RCT of the same treatment. Furthermore, effect sizes on measures of outcomes particularly relevant to this population of mass violence survivors such as functional impairment, use of alcohol and drugs to cope, and use of social support to cope, were also medium to large. PMID- 17350591 TI - Asynchrony in the growth and motility responses to environmental changes by individual bacterial cells. AB - Knowing how individual cells respond to environmental changes helps one understand phenotypic diversity in a bacterial cell population, so we simultaneously monitored the growth and motility of isolated motile Escherichia coli cells over several generations by using a method called on-chip single-cell cultivation. Starved cells quickly stopped growing but remained motile for several hours before gradually becoming immotile. When nutrients were restored the cells soon resumed their growth and proliferation but remained immotile for up to six generations. A flagella visualization assay suggested that deflagellation underlies the observed loss of motility. This set of results demonstrates that single-cell transgenerational study under well-characterized environmental conditions can provide information that will help us understand distinct functions within individual cells. PMID- 17350592 TI - Inactivation of Mxi1 induces Il-8 secretion activation in polycystic kidney. AB - The Mxi1 proteins are biochemical and biological antagonists of c-myc oncoprotein. It has been reported that the overexpression pattern of c-myc might be similar to a molecular feature of early and late stages of human autosomal dominant polycystic kidney disease. We identified the cyst phenotype in Mxi1 deficient mice aged 6-12 months using H&E staining. Some chemokines containing a protein domain similar to human IL-8, which is associated with the inflammatory response, were subsequently selected from the up-regulated genes. We confirmed the expression level of these chemokines and measured protein concentrations of IL-8 using ELISA in the Mxi1-knockdown cells. IL-8 was found to be significantly increased in Mxi1-knockdown cells. We found that p38 MAP kinase activation was involved in the signal transduction of the Mxi1-inactivated secretion of IL-8. Therefore, we could suggest that the inactivation of Mxi1 leads to the inflammatory response and has the potential to induce polycystic renal disease. PMID- 17350593 TI - Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis. AB - Dietary model of steatohepatitis was established by feeding mice a methionine choline deficient (MCD) diet. Mice on MCD or control diet for 3 weeks were treated with or without NO-1886, a newly synthetic lipoprotein lipase (LPL) activator. In a separate experiment, NO-1886 was given after pre-treatment with 3 weeks of MCD diet. NO-1886 significantly reduced MCD-induced inflammation by repressing levels of hepatic lipid peroxides and pro-inflammatory tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). In addition, NO-1886 dampened hepatic steatosis via accelerating fatty acid oxidation caused by enhanced expression of PPARalpha, cytochrome P450-10 (Cyp4a10), and Acyl-CoA oxidase (ACO). It failed to regulate genes of fatty acid uptake and synthesis pathways. In conclusion, NO-1886 ameliorated and induced regression of experimental steatohepatitis via increasing endogenous LPL activation resulting in suppression on pro-inflammatory factors and reduction of hepatic fatty acids. These findings indicate that NO-1886 is a potential therapeutic agent for steatohepatitis. PMID- 17350594 TI - Stabilization of Snail by HuR in the process of hydrogen peroxide induced cell migration. AB - Snail functions as a key regulator in the induction of a phenotypic change called epithelial to mesenchymal transition (EMT). Aberrant expression of Snail prevails in the onset and development of tumor. Here, we have observed increased expression of Snail under the treatment of hydrogen peroxide (H(2)O(2)). Investigation into the underlying mechanisms revealed that stabilization of Snail mRNA contributes partially to this process. H(2)O(2)-induced the luciferase activity of the reporter construct contains the 3'UTR of Snail. Deletion of the AU-rich elements in the UTR eliminated the response of the reporter to H(2)O(2), suggesting the potential role of HuR in the process. Lowering of endogenous HuR levels through knockdown of HuR by siRNA greatly reduced the inducability and half-life of Snail mRNA, which consequently inhibited the downregulation of E cadherin by H(2)O(2). Our findings indicate that HuR plays a major role in regulating H(2)O(2)-induced Snail expression by enhancing Snail mRNA stability, which in turn enhances cell migrating ability through repressing expression of E cadherin. PMID- 17350595 TI - Shed gangliosides provide detergent-independent evidence for type-3 glycosynapses. AB - Membrane microdomains, or rafts, at the plasma membrane have been invoked to explain many cellular processes. Protein-protein interactions within such microdomains including, for example, the tetraspanin web are reported to provide a scaffold for signal transduction. However, the nature of such protein-protein interactions is not fully elucidated. Hakomori [S.I. Hakomori, The glycosynapse, Proc. Natl. Acad. Sci. USA 99 (2002) 225-232] has advanced the concept that glycosphingolipids, particularly gangliosides, provide the intermediary link between transmembrane receptors and signal transducers and has redefined membrane rafts as Type-1, -2 or -3 glycosynapses. Here, using simple immunofluorescent analysis of the ganglioside complexes naturally released from cellular microprocesses (termed "footprints") we show that the ganglioside can determine the nature of protein-protein associations. Specifically, we demonstrate that CD36 and the tetraspanin CD151, both of which interact with beta1 integrins, associate together only in the presence of the gangliosides GD2/GD3. These results substantiate the glycosynapse hypothesis and suggest that the nature of the tetraspanin web may be determined by gangliosides. PMID- 17350596 TI - Sp1 and Sp3 regulate basal transcription of the survivin gene. AB - Survivin, a unique member of the inhibitor of apoptosis protein family, is overexpressed in many cancers and considered to play an important role in oncogenesis. In this study, we cloned and identified the proximal 269 bp promoter of survivin gene, which exhibited strong promoter activity in HeLa cells. The TATA-less, GC-rich promoter contains 7 putative binding sites for Sp1, two of which (one at position -148 to -153, the other at position -127 to -140) are essential in regulating basal survivin promoter activity. Not only Sp1 but also Sp3 can activate the survivin promoter, which were proven by EMSA, blocking Sp1 or Sp3 using RNAi or mithramycin treatment of HeLa cells, and overexpression of Sp1 or Sp3. Our results collectively suggest that Sp1 cooperates with Sp3 to regulate survivin promoter activity. PMID- 17350597 TI - The bean PvSR2 gene produces two transcripts by alternative promoter usage. AB - The bean (Phaseolus vulgaris) stress-related gene number 2 (PvSR2) is heavy metal inducible. Here, the intron of PvSR2 (I-PvSR) within the coding sequence was isolated and characterized. I-PvSR exhibited a weak and constitutive promoter activity and enhanced the PvSR2 promoter activity in transiently transformed tobacco protoplasts. The transcription start site of I-PvSR promoter was mapped 72 bp upstream of the 3'-splice site. The shorter PvSR2 transcript (768nt) in bean is generated from this intronic promoter and lacks the last 56 bases of 3' end sequence of longer PvSR2 transcript (829nt) by utilizing an alternative polyadenylation site. Quantitative competitive PCR analysis further revealed that two transcripts were differently accumulated in response to Hg(2+)-exposure and the longer transcript was more abundant than the shorter one. These results demonstrate an additional non-metal inducible transcription of PvSR2 via alternative intronic promoter usage and provide new insights into expression mechanism of metal inducible gene. PMID- 17350598 TI - Apoptosis and inactivation of the PI3-kinase pathway by tetrocarcin A in breast cancers. AB - A survival kinase, Akt, is a downstream factor in the phosphatidylinositide-3' kinase-dependent pathway, which mediates many biological responses including glucose uptake, protein synthesis and the regulation of proliferation and apoptosis, which is assumed to contribute to acquisition of malignant properties of human cancers. Here we find that an anti-tumor antibiotic, tetrocarcin A, directly induces apoptosis of human breast cancer cells. The apoptosis is accompanied by the activation of a proteolytic cascade of caspases including caspase-3 and -9, and concomitantly decreases phosphorylation of Akt, PDK1, and PTEN, a tumor suppressor that regulates the activity of Akt through the dephosphorylation of polyphosphoinositides. Tetrocarcin A affected neither expression of Akt, PDK1, or PTEN, nor did it affect the expression of Bcl family members including Bcl-2, Bcl-X(L), and Bax. These results suggest that tetrocarcin A could be a potent chemotherapeutic agent for human breast cancer targeting the phosphatidylinositide-3'-kinase/Akt signaling pathway. PMID- 17350599 TI - Transcription of the mitochondrial citrate carrier gene: role of SREBP-1, upregulation by insulin and downregulation by PUFA. AB - In this study we investigated the transcriptional role of the sterol regulatory element (SRE) present in the promoter of the mitochondrial citrate carrier (CIC). We show that wild-type (but not mutated) CIC SRE cloned in front of the luciferase promoter confers transcriptional activation of the gene reporter. We also demonstrate that insulin activates, and polyunsaturated fatty acids (PUFA) inhibit, the gene reporter activity driven by the CIC promoter containing wild type (but not mutated) SRE. Finally, both insulin treatment and overexpression of SRE binding protein (SREBP-1) increase the CIC transcript and protein levels, whereas PUFA have an opposite effect. These results show that SRE/SREBP-1 play a role in the transcriptional regulation of CIC by insulin and PUFA. PMID- 17350600 TI - NF-Y and Sp1 are involved in transcriptional regulation of rat SND p102 gene. AB - SND p102 is a rat liver endoplasmic reticulum cholesterol ester hydrolase recently described as a member of a conserved family of transcriptional coactivators that promotes phospholipid secretion into lipoproteins when overexpressed in hepatocytes. In this work, we report first evidence for a mechanism of transcriptional regulation for the SND p102 (Snd1) gene. Promoter activity of 5' deletion fragments determined in human HepG2 and rat McA-RH7777 hepatoma cells by luciferase reporter gene assays showed a minimal promoter involving two inverted CCAAT boxes. EMSA demonstrated specific binding of Sp1 to GC boxes in the proximal, highly active promoter region besides that of NF-Y to CCAAT boxes reported earlier. Site-directed disruption of such CCAAT and GC boxes led to reduction in transcriptional activity, confirming the functional implication of NF-Y and Sp1 in SND p102 gene transcription. PMID- 17350601 TI - Enhanced antibody affinity to Japanese encephalitis virus E protein by phage display. AB - Obtaining antibodies with high affinity and specificity against antigens are required for the development of therapeutic and diagnostic antibodies. In this study, the contributions to binding affinity in the CDR2 and CDR3 regions of two monoclonal antibodies E3.3 and 2H2 were investigated by random mutagenesis in a phage-display synthetic oligonucleotide library. One high-affinity clone (CDR3 30) was obtained with a 3-fold increase of the dissociation constant, resulting from the changes in amino acids at residues 95, 97, and 98 in the CDRH3 region. Analysis of the predicted structure by modeling suggested that the contributions of mutated residues in the CDR3 region to the binding affinity involved not only complementarity between antigen and CDR3, but also interaction between heavy and light chains. The information gained from this study may benefit the design of vaccines and therapeutic antibodies against Japanese encephalitis virus infection. PMID- 17350603 TI - Characterization of mouse neuronal Ca2+/calmodulin kinase II inhibitor alpha. AB - We have overexpressed an 8.5-kDa mouse Ca(2+)/calmodulin kinase II inhibitor alpha protein (mCaMKIINalpha) in Escherichia coli and demonstrate that the recombinant protein is a potent inhibitor of Ca(2+)/calmodulin kinase II (CaMKII) in vitro. However, antibodies raised against recombinant mCaMKIINalpha react with an approximately 37-kDa protein present in mouse brain. The pattern of expression of the approximately 37-kDa protein is similar to that of mCaMKIINalpha mRNA as both are expressed in normal but not Japanese encephalitis virus (JEV)-infected mouse brain. Subcellular localization studies indicate that the approximately 37 kDa protein is present in the post-synaptic density (PSD) where mCaMKIIalpha is known to perform key regulatory functions. We conclude that the approximately 37 kDa protein identified in this study is mCaMKIINalpha and its localization in the PSD indicates a novel role for this protein in the regulation of neuronal CaMKIIalpha. PMID- 17350602 TI - DeltaPKC mediates microcerebrovascular dysfunction in acute ischemia and in chronic hypertensive stress in vivo. AB - Maintaining cerebrovascular function is a priority for reducing damage following acute ischemic events such as stroke, and under chronic stress in diseases such as hypertension. Ischemic episodes lead to endothelial cell damage, deleterious inflammatory responses, and altered neuronal and astrocyte regulation of vascular function. These, in turn, can lead to impaired cerebral blood flow and compromised blood-brain barrier function, promoting microvascular collapse, edema, hemorrhagic transformation, and worsened neurological recovery. Multiple studies demonstrate that protein kinase C (PKC), a widely expressed serine/threonine kinase, is involved in mediating arterial tone and microvascular function. However, there is no clear understanding about the role of individual PKC isozymes. We show that intraperitoneal injection of deltaV1-1-TAT(47-57) (0.2 mg/kg in 1 mL), an isozyme-specific peptide inhibitor of deltaPKC, improved microvascular pathology, increased the number of patent microvessels by 92% compared to control-treated animals, and increased cerebral blood flow by 26% following acute focal ischemia induced by middle cerebral artery occlusion in normotensive rats. In addition, acute delivery of deltaV1-1-TAT(47-57) in hypertensive Dahl rats increased cerebral blood flow by 12%, and sustained delivery deltaV1-1-TAT(47-57) (5 uL/h, 1 mM), reduced infarct size by 25% following an acute stroke induced by MCA occlusion for 90 min. Together, these findings demonstrate that deltaPKC is an important therapeutic target for protection of microvascular structure and function under both acute and chronic conditions of cerebrovascular stress. PMID- 17350604 TI - Pattern recognition analysis of polyamines in the plasma of rat models with adenovirus infection. PMID- 17350605 TI - Evaluation of the roles of adenosine deaminase and xanthine oxidase in reperfusion injury in patients with myocardial infarction. PMID- 17350606 TI - Serum level of ornithine carbamoyltransferase is influenced by the state of Kupffer cells. AB - BACKGROUND: The ratio of ornithine carbamoyltransferase (OCT) to alanine aminotransferase (ALT) or glutamate dehydrogenase (GDH) in serum has been suggested as an indicator for the diagnosis of hepatocellular carcinoma and alcoholic liver disease, respectively. However, the mechanisms responsible for the increase in these ratios are still unclear. METHODS: Wistar rats were pretreated with lipopolysaccharide (LPS) or gadolinium chloride (GD) before being administered with thioacetamide (TAA, 200 mg/kg, ip). Serum OCT and ALT levels were compared with control values. Half-lives of the enzymes in circulation were evaluated after the intravenous injection of the purified enzymes into rats with or without the pretreatment. RESULTS: The serum level of OCT at 24 h after the administration of TAA was significantly lower in the LPS-treated group, and not influenced by pretreatment with GD. The half-life of OCT was prolonged from 1.06+/-0.14 to 2.07+/-0.29 h (p<0.05) by the pretreatment with GD, but not influenced by the administration of LPS. No change was observed in the clearance of GDH or ALT among the pretreatments. CONCLUSIONS: Leakage into and clearance from the circulation of OCT are influenced by whether Kupffer cells are activated or not. OCT alone or in combination with other markers may be a useful indicator for Kupffer cell activation as well as mitochondrial damage in hepatic cells. PMID- 17350607 TI - Determination of butyrylcholinesterase (BChE) phenotypes to predict the risk of prolonged apnea in persons receiving succinylcholine in the healthy population of western Iran. AB - OBJECTIVE: The best known clinical application of serum BChE assay is to predict abnormally prolonged apnea following the application of the muscle relaxant succinylcholine. The aim of the present study was to assess the frequency of BChE phenotypes and to predict the risk of apnea for those receiving succinylcholine among the residents in western Iran. METHODS: We examined the frequency of nine BChE phenotypes in 1548 volunteers including 816 males and 732 females with the mean age of 35+/-15 years from an apparently healthy group living in western Iran. The frequencies of BChE phenotypes were determined using BChE activity measurements and by inhibition with dibucaine, fluoride, and the compound Ro2 0683 (Hoffman-La-Roche). RESULTS: The reference range for serum total BChE activity was 4600-14000 U/L (using butyrylthiocholine iodide as substrate). The mean value obtained for men (9030 U/L) was significantly (p<0.05) higher than that for women (8550 U/L). The frequencies of four alleles U, A, F, S were calculated to be 0.9826, 0.0165, 0.008 and 0.001, respectively. The frequency of phenotypes of BChE was as follows: normal phenotype (UU) 95.5%, moderate sensitive to succinylcholine including UA,US,UF phenotypes was 3.9% and hypersensitive to succinylcholine (AA, AF, AS, FF, SS) was 0.58%. CONCLUSION: This study indicates that the population of western Iran has a medium frequency of succinylcholine-sensitive individuals compared to other populations. We suggest that determination of BChE activity and phenotype by the micro automated method is well suited to pre-operative screening and detection of at-risk of prolonged apnea in persons receiving succinylcholine in the healthy population of western Iran. PMID- 17350608 TI - Synesthesia and number cognition in children. AB - Grapheme-color synesthesia, when achromatic digits evoke an experience of a specific color (photisms), has been shown to be consistent, involuntary, and linked with number concept in adults, yet there have been no comparable investigations with children. We present a systematic study of grapheme-color synesthesia in children aged between 7 and 15 years. Here we show that such children (but not children with phoneme-color synesthesia) experience involuntary difficulties in numerical tasks when digits are presented in colors incongruent with their photisms. Synesthesia in children may thus have important consequences for certain aspects of numerical cognition. PMID- 17350609 TI - Comparison of actual vs. synthesized ternary phase diagrams for solutes of cryobiological interest. AB - Phase diagrams are of great utility in cryobiology, especially, those consisting of a cryoprotective agent (CPA) dissolved in a physiological salt solution. These ternary phase diagrams consist of plots of the freezing points of increasing concentrations of solutions of cryoprotective agents (CPA) plus NaCl. Because they are time-consuming to generate, ternary diagrams are only available for a small number of CPAs. We wanted to determine whether accurate ternary phase diagrams could be synthesized by adding together the freezing point depressions of binary solutions of CPA/water and NaCl/water which match the corresponding solute molality concentrations in the ternary solution. We begin with a low concentration of a solution of CPA+salt of given R (CPA/salt) weight ratio. Ice formation in that solution is mimicked by withdrawing water from it which increases the concentrations of both the CPA and the NaCl. We compute the individual solute concentrations, determine their freezing points from published binary phase diagrams, and sum the freezing points. These yield the synthesized ternary phase diagram for a solution of given R. They were compared with published experimental ternary phase diagrams for glycerol, dimethyl sulfoxide (DMSO), sucrose, and ethylene glycol (EG) plus NaCl in water. For the first three, the synthesized and experimental phase diagrams agreed closely, with some divergence occurring as wt% concentrations exceeded 30% for DMSO and 55% for glycerol, and sucrose. However, in the case of EG there were substantial differences over nearly the entire range of concentrations which we attribute to systematic errors in the experimental EG data. New experimental EG work will be required to resolve this issue. PMID- 17350610 TI - Sox9 is required for precursor cell expansion and extracellular matrix organization during mouse heart valve development. AB - Heart valve structures derived from mesenchymal cells of the endocardial cushions (ECs) are composed of highly organized cell lineages and extracellular matrix. Sox9 is a transcription factor required for both early and late stages of cartilage formation that is also expressed in the developing valves of the heart. The requirements for Sox9 function during valvulogenesis and adult valve homeostasis in mice were examined by conditional inactivation of Sox9 using Tie2 cre and Col2a1-cre transgenes. Sox9(flox/flox);Tie2-cre mice die before E14.5 with hypoplastic ECs, reduced cell proliferation and altered extracellular matrix protein (ECM) deposition. Sox9(flox/flox);Col2a1-cre mice die at birth with thickened heart valve leaflets, reduced expression of cartilage-associated proteins and abnormal ECM patterning. Thickened valve leaflets and calcium deposits, characteristic of valve disease, are observed in heterozygous adult Sox9(flox/+);Col2a1-cre mice. Therefore, Sox9 is required early in valve development for expansion of the precursor cell population and later is required for normal expression and distribution of valvular ECM proteins. These data indicate that Sox9 is required for early and late stages of valvulogenesis and identify a potential role for Sox9 in valve disease mechanisms. PMID- 17350611 TI - Migration of volatile organic compounds from attached garages to residences: a major exposure source. AB - Vehicle garages often contain high concentrations of volatile organic compounds (VOCs) that may migrate into adjoining residences. This study characterizes VOC concentrations, exposures, airflows, and source apportionments in 15 single family houses with attached garages in southeast Michigan. Fieldwork included inspections to determine possible VOC sources, deployment of perfluorocarbon tracer (PFT) sources in garages and occupied spaces, and measurements of PFT, VOC, and CO(2) concentrations over a 4-day period. Air exchange rates (AERs) averaged 0.43+/-0.37 h(-1) in the houses and 0.77+/-0.51 h(-1) in the garages, and air flows from garages to houses averaged 6.5+/-5.3% of the houses' overall air exchange. A total of 39 VOC species were detected indoors, 36 in the garage, and 20 in ambient air. Garages showed high levels of gasoline-related VOCs, e.g., benzene averaged 37+/-39 microg m(-3). Garage/indoor ratios and multizone IAQ models show that nearly all of the benzene and most of the fuel-related aromatics in the houses resulted from garage sources, confirming earlier reports that suggested the importance of attached garages. Moreover, doses of VOCs such as benzene experienced by non-smoking individuals living in houses with attached garages are dominated by emissions in garages, a result of exposures occurring in both garage and house microenvironments. All of this strongly suggests the need to better control VOC emissions in garages and contaminant migration through the garage-house interface. PMID- 17350612 TI - Functional activation by central monoamines of human dopamine D(4) receptor polymorphic variants coupled to GIRK channels in Xenopus oocytes. AB - We studied the functional activation of different polymorphic variants of the human dopamine D(4) receptors by the three major central monoamines, dopamine, noradrenaline and serotonin. Dopamine D(4) receptors carrying two (D4.2), four (D4.4) or seven (D4.7) repeats within the third intracellular domain were co expressed with G protein-regulated inwardly rectifying potassium channels (GIRK1) in frog oocytes. All the dopamine D(4) receptor variants coupled to oocyte G(i/o) proteins and modulated co-expressed GIRK1 channels. Monoamine-induced responses were detected as increases in voltage-clamp recorded GIRK1 currents. Dopamine, noradrenaline as well as serotonin stimulated dopamine D(4) receptors. Dose response analysis showed that dopamine and noradrenaline are full agonists whereas serotonin acted as partial agonist. Dopamine was 5-fold more potent on D4.2 and D4.7 (EC(50)=1 nM) than on D4.4 (EC(50)=5 nM) suggesting that the actions of dopamine and therapeutic drugs on dopamine D(4) receptors might vary among individuals depending on their repertoire of expressed alleles. In contrast, noradrenaline and serotonin did not discriminate among dopamine D(4) receptor variants (EC(50 NA)=50 nM, EC(50 5-HT)=1.5 microM). All monoamine effects were blocked by the specific dopaminergic D(4) antagonist (S)-(-)-4-[4-[2 (Isochroman-1-yl)ethyl]piperazin-1-yl]benzenesulfonamide (PNU101387). Sequence analyses of dopamine D(4) receptors and related monoamine receptors revealed that dopamine D(4) receptors have most aminoacidic residues necessary for binding of dopamine, noradrenaline and serotonin. Our data indicate that dopamine D(4) receptors can be pharmacologically stimulated by any the three major central monoamines. PMID- 17350613 TI - The histamine H3 receptor antagonist clobenpropit enhances GABA release to protect against NMDA-induced excitotoxicity through the cAMP/protein kinase A pathway in cultured cortical neurons. AB - Using the histamine H3 receptor antagonist clobenpropit, the roles of histamine H3 receptors in NMDA-induced necrosis were investigated in rat cultured cortical neurons. Clobenpropit reversed the neurotoxicity in a concentration-dependent manner, and showed peak protection at a concentration of 10(-7) M. This protection was antagonized by the histamine H3 receptor agonist (R)-alpha methylhistamine, but not by the histamine H1 receptor antagonist pyrilamine or the histamine H2 receptor antagonist cimetidine. In addition, the protection by clobenpropit was inhibited by the GABAA receptor antagonists picrotoxin and bicuculline. Further study demonstrated that the protection by clobenpropit was due to increased GABA release. The inducible GABA release was also inhibited by (R)-alpha-methylhistamine, but not by pyrilamine or cimetidine. Furthermore, both the adenylyl cyclase inhibitor SQ-22536 and the protein kinase A (PKA) inhibitor H-89 reversed the protection and the GABA release by clobenpropit. In addition, clobenpropit reversed the NMDA-induced increase in intracellular calcium level, which was antagonized by (R)-alpha-methylhistamine. These results indicate that clobenpropit enhanced GABA release to protect against NMDA-induced excitotoxicity, which was induced through the cAMP/PKA pathway, and reduction of intracellular calcium level may also be involved. PMID- 17350614 TI - Comparison of the binding distribution of agonist and antagonist ligands for histamine H3 receptors in pig brain by quantitative autoradiography. AB - The relationship between the abundances of agonist and antagonist-binding sites for monoamine receptors is poorly established. Therefore, we used quantitative autoradiography to investigate the distribution and concentration of binding sites for histamine H(3) receptor ligands in cryostat sections of pig brain. As in other species, binding of the histamine H(3) receptor agonist [(3)H]N(alpha) methylhistamine was highly heterogeneous in the pig brain, with highest B(max) in the substantia nigra, followed by the nucleus accumbens and caudate, intermediate binding in frontal cortex, diencephalon, and mesencephalon, and absent specific binding in cerebellum: the affinity of [(3)H]N(alpha)-methylhistamine was close to 1 nM in all regions of pig brain. Thus, the saturation binding parameters for this H(3) receptor agonist in pig brain were similar to the earlier reports in rat, guinea pig, and human. The distribution of histamine H(3) receptors labeled with the receptor antagonist [(125)I]iodophenpropit in adjacent cryostat sections from the same group of pigs was very similar to that of [(3)H]N(alpha) methylhistamine. However, the B(max) of the receptor antagonist was 40% higher in the basal ganglia than was the B(max) of the receptor agonist. The K(d) for the receptor antagonist ligand was close to 0.9 nM in all regions. These results suggest that histamine H(3) receptor agonist-binding sites, i.e. those linked to intracellular G-protein, comprise a subset of the total receptor antagonist binding sites in the basal ganglia, as has been reported for dopamine D(2) receptors. PMID- 17350615 TI - Adrenal adrenaline- and noradrenaline-containing cells and celiac sympathetic ganglia are differentially controlled by centrally administered corticotropin releasing factor and arginine-vasopressin in rats. AB - The adrenal glands and sympathetic celiac ganglia are innervated mainly by the greater splanchnic nerves, which contain preganglionic sympathetic nerves that originated from the thoracic spinal cord. The adrenal medulla has two separate populations of chromaffin cells, adrenaline-containing cells (A-cells) and noradrenaline-containing cells (NA-cells), which have been shown to be differentially innervated by separate groups of the preganglionic sympathetic neurons. The present study was designed to characterize the centrally activating mechanisms of the adrenal A-cells, NA-cells and celiac sympathetic ganglia with expression of cFos (a marker for neural excitation), in regard to the brain prostanoids, in anesthetized rats. Intracerebroventricularly (i.c.v.) administered corticotropin-releasing factor (CRF) induced cFos expression in the adrenal A-cells, but not NA-cells, and celiac ganglia. On the other hand, i.c.v. administered arginine-vasopressin (AVP) resulted in cFos induction in both A cells and NA-cells in the adrenal medulla, but not in the celiac ganglia. Intracerebroventricular pretreatment with indomethacin (an inhibitor of cyclooxygenase) abolished the CRF- and AVP-induced cFos expression in all regions described above. On the other hand, intracerebroventricular pretreatment with furegrelate (an inhibitor of thromboxane A2 synthase) abolished the CRF-induced cFos expression in the adrenal A-cells, but not in the celiac ganglia, and also abolished the AVP-induced cFos expression in both A-cells and NA-cells in the adrenal medulla. These results suggest that centrally administered CRF activates adrenal A-cells and celiac sympathetic ganglia by brain thromboxane A2-mediated and other prostanoid than thromboxane A2 (probably prostaglandin E2)-mediated mechanisms, respectively. On the other hand, centrally administered AVP activates adrenal A-cells and NA-cells by brain thromboxane A2-mediated mechanisms in rats. PMID- 17350616 TI - Human estrogen receptor alpha gene is a target of Runx2 transcription factor in osteoblasts. AB - Several studies into the mechanisms involved in control of osteoblast-specific gene expression have identified Runx2 and ERalpha (estrogen receptor alpha) as essential regulators of osteoblast differentiation. Recently, interactions between Runx2 and ERalpha have been described. Here, we investigate the role of Runx2 on the regulation of ERalpha expression by determining its interaction with the F promoter, one of the multiple promoters of the human ERalpha gene and the only one active in bone. We found that, in this promoter, three Runx2-like sites are present. By electrophoretic mobility shift assay in combination with supershift and ChIP experiments, we demonstrated that Runx2 preferentially binds one of the Runx2 motifs of the F promoter. To understand whether or not they are involved in influencing F promoter activity, different promoter-reporter deletion and mutation constructs were transiently transfected into human osteoblastic cells. Comparison of luciferase activities allowed the identification of a prevalent negative role of a sequence context, within the -117,877/-117,426 region, which may be under the control of Runx2 (a) site. Finally, silencing and overexpression of endogenous Runx2 provided evidence that Runx2 has a more complex role than initially expected. In fact, Runx2 (a) and Runx2 (b) sites carried out opposite roles which are conditioned by Runx2 levels in bone cells. Therefore, the resulting F promoter activity may be tightly regulated by a dynamic interplay between these two Runx2 sites, with a predominance of negative effect of the Runx2 (a) site. PMID- 17350617 TI - Characterization of the sterol-binding domain of oxysterol-binding protein (OSBP) related protein 4 reveals a novel role in vimentin organization. AB - Oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4; also designated OSBP2 and HLM) are implicated in sterol-transport and/or sensing via binding to protein partners. The aggregation of vimentin by an N-terminal truncated variant of ORP4 (ORP4S), but not full-length ORP4L, suggested a functional interaction with this intermediate filament. Herein, we identify ORP4 domains that interact with vimentin, and determine how sterols and OSBP influence this activity. In CHO cells, ORP4L co-localized with filamentous vimentin but extensive remodeling of vimentin filaments required mutation of a leucine repeat motif (amino acids 361-382) adjacent to the oxysterol-binding domain. Similarly, the absence of the leucine repeat in ORP4S 418-878 resulted in co-localization with aggregated vimentin filaments, suggesting that both the sterol-binding domain and leucine repeat are involved. Transient expression of OSBP leucine repeat mutants also promoted vimentin aggregation by a mechanism involving heterodimerization with ORP4L. Glutathione S-transferase (GST)-ORP4 380-878 bound vimentin, cholesterol and 25-hydroxycholesterol in vitro. However, sterol-binding or a mutation that ablated sterol-binding did not influence the interaction of GST-ORP4 with vimentin. Thus the sterol-binding domain of ORP4 binds vimentin, cholesterol and oxysterols, and interacts with the filamentous vimentin network. PMID- 17350618 TI - Effect of excess synthesis of extracellular matrix components by trabecular meshwork cells: possible consequence on aqueous outflow. AB - The extracellular matrix (ECM) of the trabecular meshwork (TM) is an important determinant of its functional properties. This study was performed to investigate whether overexpression of ECM components, laminin (LM) and collagen type IV (Col) by TM cells may play a role in the development of outflow resistance. To determine the effect of excess LM and Col expression on cell monolayer permeability, an in vitro cell culture model was used in which overexpression of the two ECM components, LM and Col, was induced by high glucose (HG) (30 mM) or 0.1 microM dexamethasone (D) in bovine and human trabecular meshwork (BTM and HTM) cells. Western blot analysis and immunofluorescence staining confirmed increased LM and Col synthesis in cells exposed to HG or D. Increased level of LM and Col protein resulted in reduced cell monolayer permeability. Transfection with antisense oligos (AS-oligos) targeted against LM or Col inhibited HG- or D induced LM and Col gene overexpression in TM cells with concomitant increase in permeability. The AS-oligo strategy was effective in reducing LM or Col level in the TM cells in all conditions tested in this study. These findings suggest that increased LM and Col deposition in the outflow pathway may cause resistance to aqueous outflow and contribute to the development of primary open angle glaucoma (POAG). PMID- 17350619 TI - Schistosoma mansoni: expression of Fes-like tyrosine kinase SmFes in the tegument and terebratorium suggests its involvement in host penetration. AB - Protein Tyrosine Kinases (PTKs) are important molecules in intra- and inter cellular communication, playing a major role in signal transduction processes. We have previously identified and characterized the molecular structure of a new PTK in Schistosoma mansoni, SmFes. SmFes exhibits the characteristic features of Fes/Fps protein tyrosine kinase subfamily of which it is the first member described in helminths. Herein, we show that genes orthologous to SmFes are also present in other Schistosoma species and the transcript is detected in Schistosoma japonicum. The SmFes protein was detected at all the main life-cycle stages and was most abundant in cercariae and newly-transformed schistosomula. However, no protein was detected in schistosomula maintained in vitro for 7 days. By immunolocalization assays we showed that SmFes is particularly concentrated at the terebratorium of miracidia and tegument of cercaria and schistosomula skin stage. These findings suggest that SmFes may play a role in signal transduction pathways involved in larval transformation after penetration into intermediate and definitive hosts. PMID- 17350620 TI - The role of Asp-295 in the catalytic mechanism of Leuconostoc mesenteroides sucrose phosphorylase probed with site-directed mutagenesis. AB - Replacements of Asp-295 by Asn (D295N) and Glu (D295E) decreased the catalytic center activity of Leuconostoc mesenteroides sucrose phosphorylase to about 0.01% of the wild-type level (k(cat)=200s(-1)). Glucosylation and deglucosylation steps of D295N were affected uniformly, approximately 10(4.3)-fold, and independently of leaving group ability and nucleophilic reactivity of the substrate, respectively. pH dependences of the catalytic steps were similar for D295N and wild-type. The 10(5)-fold preference of the wild-type for glucosyl transfer compared with mannosyl transfer from phosphate to fructose was lost in D295N and D295E. Selective disruption of catalysis to glucosyl but not mannosyl transfer in the two mutants suggests that the side chain of Asp-295, through a strong hydrogen bond with the equatorial sugar 2-hydroxyl, stabilizes the transition states flanking the beta-glucosyl enzyme intermediate by > or = 23kJ/mol. PMID- 17350621 TI - Glu 69 is essential for the high sensitivity of muscle fructose-1,6 bisphosphatase inhibition by calcium ions. AB - Muscle fructose-1,6-bisphosphatase (FBPase) is highly sensitive toward inhibition by AMP and calcium ions. In allosteric inhibition by AMP, a loop 52-72 plays a decisive role. This loop is a highly conservative region in muscle and liver FBPases. It is feasible that the same region is involved in the inhibition by calcium ions. To test this hypothesis, chemical modification, limited proteolysis and site directed mutagenesis Glu(69)/Gln were employed. The chemical modification of Lys(71-72) and the proteolytic cleavage of the loop resulted in the significant decrease of the muscle FBPase sensitivity toward inhibition by calcium ions. The mutation of Glu(69)-->Gln resulted in a 500-fold increase of muscle isozyme I(0.5) vs. calcium ions. These results demonstrate the key role that the 52-72 amino acid loop plays in determining the sensitivity of FBPase to inhibition by AMP and calcium ions. PMID- 17350622 TI - A zinc-finger like metal binding site in the nucleosome. AB - UV spectroscopy demonstrated that chicken mononucleosomes bind Co(II) and Zn(II) ions at submicromolar concentrations in a tetrahedral mode, at a conserved zinc finger-like site, composed of Cys110 and His113 residues of both H3 molecules. Neither of these metal ions substituted for another, indicating a limited binding reversibility. Molecular modeling indicated that the tetrahedral site is formed by unhindered rotations around Calpha-Cbeta bonds in the side chains of the zinc binding residues. The resulting local rearrangement of the protein structure shields the bound metal ion from the solvent, explaining the observed lack of reversibility of the binding. Consequences of these findings for zinc homeostasis, metal toxicology and nucleosomal regulation are discussed. PMID- 17350624 TI - Membrane protein assembly patterns reflect selection for non-proliferative structures. AB - Membrane proteins that regulate solute movement are often built from multiple copies of an identical polypeptide chain. These complexes represent striking examples of self-assembling systems that recruit monomers only until a prescribed level for function is reached. Here we report that three modes of assembly - distinguished by sequence and stoichiometry - describe all helical membrane protein complexes currently solved to high resolution. Using the 13 presently available non-redundant homo-oligomeric structures, we show that two of these types segregate with protein function: one produces energy-dependent transporters, while the other builds channels for passive diffusion. Given such limited routes to functional complexes, membrane proteins that self-assemble exist on the edge of aggregation, susceptible to mutations that may underlie human diseases. PMID- 17350623 TI - PKCzetaII is a target for degradation through the tumour suppressor protein pVHL. AB - PKCzetaII is a rapidly degraded variant of PKCzeta that suppresses epithelial cell polarisation. It is shown here that PKCzetaII is a target for the E3 ligase and tumour suppressor Von Hippel-Lindau protein (pVHL). Deletion studies demonstrate that the C-terminal region is required for the pVHL and proteasome dependent turnover of PKCzetaII, however it is the N-terminal PB1 domain of PKCzetaII that is required for pVHL complex formation. Reciprocal deletion studies define the pVHL effector domain as the dominant PKCzetaII binding site. The results indicate that pVHL recruits PKCzetaII via its PB1 domain and causes ubiquitination and degradation via the distal C-terminus of PKCzetaII. PMID- 17350625 TI - Metabolism controls dimerization of the chloroplast FoF1 ATP synthase in Chlamydomonas reinhardtii. AB - Dimers and oligomers of F-type ATP synthases have been observed previously in mitochondria of various organisms and for the CF(o)F(1) ATP synthase of chloroplasts of Chlamydomonas reinhardtii. In contrast to mitochondria, however, dimers of chloroplast ATP synthases dissociate at elevated phosphate concentration. This suggests a regulation by cell physiological processes. Stable isotope labeling of living cells and blue-native PAGE have been employed to quantitate changes in the ratio of monomeric to dimeric CF(o)F(1) ATP synthase. Chlamydomonas reinhardtii cells were cultivated photoautotrophically in the presence of (15)N and photomixotrophically at natural (14)N abundance, respectively. As compared to photoautotrophic growth, an increased assembly of ATP synthase dimers on the expense of preexisting monomers during photomixotrophic growth was observed, demonstrating a metabolic control of the dimerization process. PMID- 17350626 TI - (-)-Epigallocatechin gallate suppresses endothelin-1-induced interleukin-6 synthesis in osteoblasts: inhibition of p44/p42 MAP kinase activation. AB - We previously showed that endothelin-1 (ET-1) stimulates the synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells, and that protein kinase C (PKC)-dependent p44/p42 mitogen-activated protein (MAP) kinase plays a part in the IL-6 synthesis. In the present study, we investigated the effect of (-)-epigallocatechin gallate (EGCG), one of the major flavonoids containing in green tea, on ET-1-induced IL-6 synthesis in osteoblasts and the underlying mechanism. EGCG significantly reduced the synthesis of IL-6 stimulated by ET-1 in MC3T3-E1 cells as well primary cultured mouse osteoblasts. SB203580, a specific inhibitor of p38 MAP kinase, but not SP600125, a specific SAPK/JNK inhibitor, suppressed ET-1-stimulated IL-6 synthesis. ET-1-induced phosphorylation of p38 MAP kinase was not affected by EGCG. On the other hand, EGCG suppressed the phosphorylation of p44/p42 MAP kinase induced by ET-1. Both the IL-6 synthesis and the phosphorylation of p44/p42 MAP kinase stimulated by 12 O-tetradecanoylphorbol 13-acetate (TPA), a direct activator of PKC, were markedly suppressed by EGCG. The phosphorylation of MEK1/2 and Raf-1 induced by ET-1 or TPA were also inhibited by EGCG. These results strongly suggest that EGCG inhibits ET-1-stimulated synthesis of IL-6 via suppression of p44/p42 MAP kinase pathway in osteoblasts, and the inhibitory effect is exerted at a point between PKC and Raf-1 in the ET-1 signaling cascade. PMID- 17350627 TI - Predominantly buried residues in the response regulator Spo0F influence specific sensor kinase recognition. AB - Several alanine mutations in the response regulator Spo0F induce hypersporulation in Bacillus subtilis. L66A, I90A and H101A mutants are purported to be involved in contacts stabilizing the orientation of the alpha4-helix and hence the beta4 alpha4 kinase recognition loop. Y13A is thought to affect the orientation of the alpha1-helix and consequently phosphatase action. Using comparative NMR chemical shift analyses for these mutants, we have confirmed these suppositions and isolated residues in Spo0F critical in sensor kinases discrimination. In addition, we discuss how buried residues and intra-protein communication networks contribute to precise molecular recognition by ensuring that the correct surface is presented. PMID- 17350628 TI - Differential requirement for the translocation of clostridial binary toxins: iota toxin requires a membrane potential gradient. AB - Clostridial binary toxins, such as Clostridium perfringens Iota and Clostridium botulinum C2, are composed of a binding protein (Ib and C2-II, respectively) that recognizes distinct membrane receptors and mediates internalization of a catalytic protein (Ia and C2-I, respectively) with ADP-ribosyltransferase activity that depolymerizes the actin cytoskeleton. After internalization, it was found that C2 and Iota toxins were not routed to the Golgi apparatus and exhibited differential sensitivity to inhibitors of endosome acidification. While the C2-I component of C2 toxin was translocated into the cytosol from early endosomes, translocation of the Ia component of Iota toxin occurred between early and late endosomes, was dependent on more acidic conditions, and uniquely required a membrane potential gradient. PMID- 17350630 TI - Design, implementation, and testing of a single axis levitation system for the suspension of a platform. AB - This paper describes the design and implementation of a single axis DC attraction type suspension system, where a platform (vehicle structure) of around 14 kg mass is made to remain suspended at the desired operating gap under a ferromagnetic guide-way. The prototype has four electromagnetic actuators of attraction type and four inductive gap sensors, all located at the corners of the platform. The four actuators are controlled independently through four identical controllers, and the stable levitation of the platform is achieved through the single input and single output (SISO) control of each air-gap. The emphasis of this work is on the design and development of the switched mode power amplifier cum controller unit for the four actuators. The proposed single switch-based power circuit simplifies the overall hardware, and it can be extended to any number of magnet coils. A cascade lead compensation control scheme utilizing an inner current loop and outer position loop has been designed and implemented for the stabilization of such a highly unstable and strongly nonlinear system. The prototype has been successfully tested, and stable levitation was demonstrated with the desired operating gap. PMID- 17350629 TI - Effects of synthetic conjugated estrogens A on sleep quality in postmenopausal women with nocturnal diaphoresis and/or hot flushes: a pilot study. AB - In a single-center, double-blind, placebo-controlled pilot study, patients who received 0.625 mg daily of synthetic conjugated estrogens A experienced a statistically significant reduction in the average number of hot flushes and galvanic skin responses. The polysomnographic change in sleep measures did not reach statistical significance, but the data suggest an overall improvement in sleep quality in the treatment group. PMID- 17350631 TI - Lysophosphatidylcholine contents in plasma LDL in patients with type 2 diabetes mellitus: relation with lipoprotein-associated phospholipase A2 and effects of simvastatin treatment. AB - Increased lipoprotein-associated PLA(2) (Lp-PLA(2)) predicts the future development of cardiovascular diseases. Although lysophosphatidylcholine (lyso PC) produced by Lp-PLA(2) may contribute to its proatherogenic activity, the relation between Lp-PLA(2) and lyso-PC content in LDL remains unclarified. We determined the correlation between lyso-PC content in LDL and serum concentrations of Lp-PLA(2), chemokines, oxidative and inflammatory markers and microvascular complications in 32 patients with type 2 diabetes mellitus free of macroangiopathy. We also investigated the effect of simvastatin treatment on Lp PLA(2) and lyso-PC content in 26 hypercholesterolemic patients with type 2 diabetes mellitus. 1-palmitoyl lyso-PC was measured using electrospray ionization liquid chromatography/mass spectrometry and Lp-PLA(2) by ELISA. Lyso-PC content in LDL was significantly higher in diabetic patients than in control healthy subjects. Lyso-PC content correlated significantly with Lp-PLA(2) levels (r=0.56, p<0.0001), and was significantly higher in patients with preproliferative or proliferative retinopathy and those with nephropathy than the control. Simvastatin treatment reduced serum Lp-PLA(2) and lyso-PC content in LDL. Our findings suggest that Lp-PLA(2) has the proatherogenic activity by contributing to the production of lyso-PC in circulating LDL. PMID- 17350632 TI - Subclinical coronary atherosclerosis and resting ECG abnormalities in an unselected general population. AB - OBJECTIVES: Exposure to cardiovascular (CV) risk factors may result in coronary atherosclerosis and myocardial disease, which is reflected in the extent of coronary artery calcification (CAC) and resting ECG abnormalities, respectively. We studied the association of CAC with ECG abnormalities in a general population without myocardial infarction or revascularization. METHODS: The total cohort of 4814 subjects (45-75 years) were randomly selected from the general population for the Heinz Nixdorf Recall Study, an ongoing study designed to assess the prognostic value of modern risk stratification methods. In addition to measuring standard risk factors, digitized resting ECGs and the EBT-based Agatston score were obtained. Subjects were separated into those without (n=1929) and with CV disease (CVD) or treated risk factors (tRF) (n=2558). RESULTS: In both groups, a positive CAC-score was more frequent and CAC-scores were higher in men and women with ECG abnormalities as compared to those with normal ECGs (p<0.05 each). In persons without CVD/tRF, a CAC > or =75th percentile was more frequent in those with LVH (42.4%) and QTc >440 ms (34.2%) as compared to normal ECGs (23.0%, p<0.01 for both). In persons with CVD/tRF, a CAC-score > or =75th percentile was found in subjects with A-Fib (46.3%), borderline-LVH (39.1%), ECG signs of MI (40.5%) and major ECG abnormalities (40.3%) versus 31.2% in those with normal ECGs (p<0.03 for all). In multivariate analysis, LVH (p=0.025) and major ECG abnormalities (p=0.04) remained independently associated with CAC in subjects without and with CVD/tRF, respectively. CONCLUSIONS: ECG-based evidence of myocardial disease is often associated with an elevated CAC burden, suggesting a link between epicardial and myocardial manifestations of risk factor exposure. The association of CAC burden with different ECG abnormalities in different clinical groups may have implications for the interpretation of the resting ECG and CAC burden in risk stratification. PMID- 17350633 TI - Hypercholesterolemia is associated with visual field alterations detectable with computerized perimetry. AB - Computerized perimetry analysis of the visual field enables the capacity of the visual cortex to process the electric impulse received from the eyeball to be detected. Considering that hypercholesterolemia can cause cognitive worsening by altering the functioning of the cerebral cortex, we attempted to determine whether it can affect the cortical processing of the visual stimuli, as detected by computerized perimetry. We undertook computerized perimetry analysis of 208 male and female patients (mean age, 48.5 years) with plasma low density lipoprotein (LDL) cholesterol concentrations above 3.36 mmol/L and compared the results with the same number of matched controls with LDL cholesterol concentrations below 3.36 mmol/L. No subject had any neuro-ophthalmological disease that could have affected the results. A Humphrey 745 computerized perimetry device was used to measure the mean deviation, the pattern standard deviation, the corrected pattern standard deviation, short-term fluctuations and the foveal threshold. Compared with the control subjects, the patients with hypercholesterolemia showed worsening in all the perimetry variables analyzed. Moreover, we also found a direct association between plasma LDL cholesterol concentrations and the perimetry alterations, and an inverse association between these alterations and the figures for HDL cholesterol. Our data show that computerized perimetry can detect alterations in the visual field of persons with hypercholesterolemia, suggesting that increased plasma concentrations of cholesterol may have a negative influence on the visual neuron cells. PMID- 17350634 TI - Separation of amino acids, peptides and corresponding Amadori compounds on a silica column at elevated temperature. AB - Maillard reaction of glucose with amino acids and peptides has become a very important experimental model in the food flavor and pharmaceutical industries for better understanding the mechanism of food flavor generation and drug stability. Because of the amino acid and sugar functional groups present in their structures, most of the reaction components formed during the initial stages of Maillard reaction as well as the substrates are relatively polar. These compounds are poorly retained on a conventional reversed phase column. While polar stationary phases like HILIC column do provide better retention for these polar components, method selectivity could still be a challenge due to the structural similarity between these analytes. In this report, parameters such as pH, mobile phase composition and temperature were investigated using different brands of bare silica columns in order to separate glycine (G), diglycine (DG), triglycine (TG), and the corresponding Amadori compounds of glucose-glycine (GG), glucose diglycine (GDG) and glucose-triglycine (GTG). An excellent separation for glycine, glycine peptides and their Amadori compounds was obtained on a bare silica column at an elevated temperature. PMID- 17350635 TI - Direct determination of free cyanide in drinking water by ion chromatography with pulsed amperometric detection. AB - Cyanide is a regulated contaminant in drinking water in the United States. This paper describes an ion chromatography method with pulsed amperometric detection (PAD) that directly determines free cyanide in drinking water. Samples are treated with sodium hydroxide to stabilize cyanide and with a cation-exchange cartridge to remove transition metals. Cyanide is separated by anion-exchange chromatography and detected by PAD with a waveform optimized for cyanide and used with a disposable silver working electrode. The recovery of cyanide spiked into five water samples was >80%. With an MDL of 1.0 microg/L, this method determines cyanide concentrations well below the reporting limits for free cyanide in drinking water. PMID- 17350636 TI - Application of high-speed counter-current chromatography for the isolation of 9' cis-neoxanthin from fresh spinach. AB - Preparative HSCCC (high-speed counter-current chromatography) could be applied for the isolation of 9'-cis-neoxanthin from a crude carotenoid extract of fresh spinach leaves. The separation was performed on a Pharma-Tech Research Corp. CCC 1000 with a solvent system composed of hexane:ethanol:water at a volume ratio of 5:5:4.5 at a flow rate of 3 mL/min and at 850 rpm, using the lower phase as mobile phase. 9'-cis-neoxanthin with a purity of up to 94% could be obtained with a single HSCCC purification step of the crude carotenoid extract. PMID- 17350637 TI - Monolithic poly[(trimethylsilyl-4-methylstyrene)-co- bis(4 vinylbenzyl)dimethylsilane] stationary phases for the fast separation of proteins and oligonucleotides. AB - In this paper the synthesis, optimisation and application of a silane based monolithic copolymer for the rapid separation of proteins and oligonucleotides is described. The monolith was prepared by thermal initiated in situ copolymerisation of trimethylsilyl-4-methylstyrene (TMSiMS) and bis(4 vinylbenzyl)dimethylsilane (BVBDMSi) in a silanised 200 microm I.D. fused silica column. Different ratios of monomer and crosslinker, as well as different ratios of micro- (toluene) and macro-porogen (2-propanol) were used for optimising the physical properties of the stationary phase regarding separation efficiency. The prepared monolithic stationary phases were characterised by measurement of permeability with different solvents, determination of pore size distribution by mercury intrusion porosimetry (MIP). Morphology was studied by scanning electron microscopy (SEM). Applying optimised conditions, a mixture comprised of five standard proteins ribunuclease A, cytochrome c, alpha-lactalbumine, myoglobine and ovalbumine was separated within 1 min by ion-pair reversed-phase liquid chromatography (IP-RPLC) obtaining half-height peak widths between 1.8 and 2.4 s. Baseline separation of oligonucleotides d(pT)(12-18) was achieved within 1.8 min obtaining half-height peak widths between 3.6 and 5.4 s. The results demonstrate the high potential of this stationary phase for fast separation of high-molecular weight biomolecules such as oligonucleotides and proteins. PMID- 17350638 TI - Preparation and characterization of polyethyleneimine modified ion-exchanger based on poly(methacrylate-co-ethylene dimethacrylate) monolith. AB - A polyethyleneimine (PEI) modified ion-exchanger was prepared based on poly(methacrylate-co-ethylene dimethacrylate) monolith cast in 100 mm x 4.6 mm I.D. stainless steel tube with heptane as the porogenic solvent at 65 degrees C for 12 h. The pores larger than 500 nm presented 85% of total pore volume of PEI monolith and provided the better permeability for separation. Bovine serum albumin (BSA) binding capacity on the column was enhanced with increasing the molecular weight of PEI, indicated that the brush ligand emanated from the surface and captured more protein by multiple binding sites. Titration experiment as well as BSA retention versus the pH of mobile phase showed that the monolith exhibited weak ion-exchange property, and recovered BSA on the monolith reached 97% when NaCl content in mobile phase was higher than 0.5 M. Frontal analysis and gradient elution of BSA indicated that PEI monolith provided the rapid mass transfer in chromatographic procedure, which made the dynamic binding capacities as well as column efficiency keep as constants at high operating flow rate. Fast separation of three mode proteins mixture (lysozyme, hemoglobin and BSA) on the monolith was achieved within 3 min at velocity of 1445 cm/h. This demonstrated the potential of PEI monolith for the rapid analysis and separation of proteins. PMID- 17350639 TI - Microwave-assisted extraction of active pharmaceutical ingredient from solid dosage forms. AB - The microwave assisted extraction (MAE) technique has been evaluated for the extraction of active pharmaceutical ingredients (API) from various solid dosage forms. Using immediate release tablets of Compound A as a model, optimization of the extraction method with regards to extraction solvent composition, extraction time and temperature was briefly discussed. Complete recovery of Compound A was achieved when samples were extracted using acetonitrile as the extraction solvent under microwave heating at a constant cell temperature of 50 degrees C for 5 min. The optimized MAE method was applied for content uniformity (single tablet extraction) and potency (multiple tablets extraction) assays of release and stability samples of two products of Compound A (5 and 25mg dose strength) stored at various conditions. To further demonstrate the applicability of MAE, the instrumental extraction conditions (50 degrees C for 5 min) were adopted for the extraction of montelukast sodium (Singulair) from various solid dosage forms using methanol-water (75:25, v/v) as the extraction solvent. The MAE procedure demonstrated an extraction efficiency of 97.4-101.9% label claim with the greatest RSD at 1.4%. The results compare favorably with 97.6-102.3% label claim with the greatest RSD at 2.9% obtained with validated mechanical extraction procedures. The system is affordable, user-friendly and simple to operate and troubleshoot. Rapid extraction process (7 min/run) along with high throughput capacity (up to 23 samples simultaneously) would lead to reduced cycle time and thus increased productivity. PMID- 17350640 TI - New process for the manufacture of alpha-1 antitrypsin. AB - We report a novel method for the extraction of alpha-1 antitrypsin (AAT) from plasma. This method uses an anion-exchange column and two metal chelate columns. The AAT is recovered in a 60% yield and a purity of over 90%. The AAT manufactured by this method was stable at 4 degrees C for 12 months without any stabilisers. Other proteins of therapeutic value and commercial interest are recoverable in good yields. The simplicity of this process makes it a suitable alternative to the traditionally employed ethanol precipitation method where high ethanol levels inactivate AAT. PMID- 17350641 TI - Dewetting self-assembly of nanoparticles into hexagonal array of nanorings. AB - Nanoparticles self-assembled into ring-shaped aggregates that were arranged in a two-dimensional (2D) hexagonal pattern. This hierarchic pattern was prepared by casting a toluene solution composed of polystyrene (PS) and Ag nanoparticles (NP). Dewetting of the thin composite layer induced the mesoscopic hexagonal array of PS-NP droplets. Within each dried droplet (dot), Ag nanoparticles self assembled into a spot- or a ring-shaped 2D superlattice alternatively depending on the size of the dot, which was controlled by the molecular weight of PS. PMID- 17350642 TI - Electrokinetics in extremely bimodal suspensions. AB - Prompted by the results obtained by Mantegazza et al. [Nature Physics 1 (2005) 103], where the electric birefringence of suspensions of elongated particles was strikingly affected by the presence of a sea of very small (size ratio lower than 10:1) colloidal spheres, we have undertaken an investigation of other electrokinetic phenomena in suspensions containing various relative concentrations of large (Teflon or polystyrene latex) and small (nanometer-sized silica spheres) colloids. We have determined the quantities that might be greatly affected by the size distribution of the particles, mainly in the presence of ac electric fields, since the response of the suspensions will show very characteristic relaxations, dominated in principle by the size of the particles. In this work, we report on measurements of the dielectric dispersion of mixed particles as a function of the concentration, ionic strength, and field frequency. The results indicate that the response is not just a simple combination of those obtained with suspensions of the individual particles, and in fact the presence of even small amounts of the small particles affects considerably the frequency response of the suspensions. PMID- 17350643 TI - Effect of interfacial rheology on model emulsion coalescence II. Emulsion coalescence. AB - In Part I, surface pressure isotherms were measured for model interfaces between a dispersed water phase and a continuous phase of asphaltenes, toluene, and heptane. Here, the coalescence rate of model emulsions prepared from the same components is determined from measured drop size distributions at 23 degrees C. A correlation is found between the initial coalescence rate and the interfacial compressibility. It is shown that the change in coalescence rate as the emulsion ages and coalesces can be predicted from surface pressure isotherm data also obtained at 23 degrees C. The stability of the emulsions was further assessed in terms of free water resolved after a treatment of heating at 60 degrees C and centrifugation. The emulsions were aged up to 24 h prior to treatment. The free water resolution appears to correlate to the "capacity for coalescence" of the interfacial film; that is, to the product of the initial film compressibility and (1-CR), where CR is the film ratio at which the film crumples. PMID- 17350645 TI - Comments on the conditions for similitude in electroosmotic flows. AB - This note provides a few comments on the conditions required for similitude between velocity and electric field in electroosmotic flows. The velocity fields of certain electroosmotic flows with relatively thin electric double layers (EDLs) are known to be irrotational in regions outside of the EDL. Under restricted conditions, the velocity field, V , can be expressed in terms of the electric field, E , as V =cE , where c is a scalar constant. The irrotationality solution is certainly unique and exact for Stokes flow, but may not be stable (or unique) for flows with Reynolds numbers significantly greater than unity. PMID- 17350644 TI - Charging and swelling of cellulose films. AB - Charging and swelling of cellulose in aqueous environments are of highest interest with respect to the performance of cellulose based products and applications. To unravel the interplay between ionization and structural features of the biopolymer hydrogel we compared non-crosslinked and crosslinked cellulose thin films based on a determination of the Donnan potential [S.S. Dukhin, R. Zimmermann, C. Werner, J. Colloid Interface Sci. 274 (2004) 309] from microslit electrokinetic (streaming potential/streaming current) experiments and layer thicknesses from ellipsometry in aqueous electrolyte solutions. The pH dependence of the Donnan potential, reflecting the ionization of carboxylic acid groups within the cellulose films, was found to be significantly different from the related trend of the streaming current which reflects the characteristics of the topmost surface of the layers: While carboxylic acid groups on the surface of the films dissociate as isolated functionalities, the electrostatic interactions of ionized groups within the cellulose layers cause an incomplete dissociation (pK shift) of the carboxylic acid and a layer expansion (swelling) in the alkaline pH range. The system was found to restrict its volume charge density even after structural restrictions (crosslinking) of the layer and at lower ionic strength of the solutions through a further decrease of the degree of dissociation of the carboxylic acid functions. These findings were attributed to the local accumulation of the carboxylic acid groups caused by preferential oxidation of the amorphous regions of the cellulose and to the ordered water structure within the layer. PMID- 17350646 TI - Partial molar volume of anionic polyelectrolytes in aqueous solution. AB - In this work the partial molar volumes (V) of different anionic polyelectrolytes and hydrophobically modified polyelectrolytes (PHM) were measured. Polymers like polymaleic acid-co-styrene, polymaleic acid-co-1-olefin, polymaleic acid-co-vinyl 2-pyrrolidone, and polyacrylic acid (abbreviated as MAS-n, PA-n-K2, AMVP, and PAA, respectively) were employed. These materials were investigated by density measurements in highly dilute aqueous solutions. The molar volume results allow us to discuss the effect of the carboxylic groups and the contributions from the comonomeric principal chain. The PAA presents the smaller V, while the largest V value was for AMVP. The V of PHM shows a linear relationship with the number of methylene groups in the lateral chain. It is found that the magnitude of the contribution per methylene group decreases as the hydrophobic character of the environment increases. PMID- 17350647 TI - Aggregation and adsorption of reactive dyes in the presence of an anionic surfactant on mesoporous aminopropyl silica. AB - A surface tension technique was used to determine the critical aggregation concentration (cac) of a yellow and a red dye in relation to the presence of the anionic surfactant sodium dodecylbenzene sulfonate (DBS) and to temperature changes in buffered aqueous solutions. The cac values of the yellow dye increase from 25 to 45 degrees C (from 41.37 to 50.32 mg L-1) and decrease from 45 to 55 degrees C (from 50.32 to 38.72 mg L-1). The cac values for the red dye/DBS aggregates decrease (from 124.52 to 88.50 mg L-1) from 25 to 55 degrees C. Adsorption of the two dyes onto a mesoporous aminopropyl silica (Sil-NH2) was also studied. The adsorption of the yellow dye increases with an increase in temperature from 25 to 55 degrees C. In the presence of DBS the adsorption on Sil NH2 for the yellow dye decreases, and for the red dye increases from 25 to 55 degrees C. Adsorptions occurred below and above the cac of the anionic dyes/DBS aggregates. Adsorption of the dyes onto Sil-NH2 fitted well to the Langmuir, Freundlich, and Redlich-Peterson adsorption models. However, in the presence of DBS, only the Freundlich model fit the experimental adsorption data at low dye concentrations (less than 400 mg L-1). In this case, the Redlich-Peterson model was only fitted to the red dye adsorption data. The magnitude of the Dubinin Radushkevich energetic parameters (E, from 7.00 to 15.00 kJ mol-1) indicates that the adsorption of the dyes onto Sil-NH2, in the absence and in the presence of DBS, is controlled by water adsorbed/dye in solution ion-exchange interactions. It is observed that the values of DeltaadsH are positive for both dyes and the values are quite similar to each other. The exception is the adsorption of the yellow dye in the presence of DBS, which is slightly exothermic. The DeltaadsG values are all negative. However, the interactions of the dyes with Sil-NH2 silica are more spontaneous in the presence of the surfactant. The positive adsorption entropy values (DeltaadsS) for the interaction of the dyes suggest that entropy is a driving force of the dye adsorptions. However, the entropic contribution is higher for the adsorptions in the presence of DBS. It was suggested that the chemical structures of the dyes play an important role in the formation of the dye/DBS aggregates and in dye adsorption onto the aminopropyl silica. PMID- 17350648 TI - An efficient and targeted gene integration system for high-level antibody expression. AB - Random integration linking genomic amplification has been used to generate desired cell lines for stable and high-level expressing recombinant antibodies. But this technique is laborious, and the expression level is unpredictable due to position effects. Here, we have constructed a cell-vector system for high-level antibody expression using an FRT/FLP strategy to overcome position effects. The key is to target the FRT sequence to chromosomal locations where there is a high rate of transcription and gene amplification, and the amplified genes can be maintained. To screen desired loci with high transcriptional activity and amplifiable capacity, dual weakened markers (selectable galactosidase and amplifiable dihydrofolate reductase, DHFR) and the FRT sequence were synchronously cloned into a plasmid. After transfection of a Chinese hamster ovary host cell line with this plasmid, we selected 20 candidate cell lines from 721 individual clones. An antibody gene-targeting vector carrying an FRT-fused hygromycin gene was constructed to target antibody genes into the chromosomal FRT site by FLP recombinase. Three out of 20 cell lines can be used as host cells for site-specific recombination. By using southern blot and fluorescence in situ hybridization (FISH), a candidate engineered cell line, number 37, was chosen. It contains a single FRT-tagged locus in its genome. FISH analysis indicated that the antibody genes were all located at the original FRT-tagged locus in the genome of the gene-targeted and gene-amplified cell lines. Three kinds of recombinant antibodies were successfully expressed in candidate cell line 37. The highest producers produced more than 200 mug/ml of the antibody in 6 days of continuous culture in a spinner flask. PMID- 17350649 TI - Cellular reactions to sedimentation and temperature stress in the Caribbean coral Montastraea cavernosa. AB - We present evidence of cellular responses to increased sedimentation and temperature in Montastraea cavernosa collected off Broward County, Florida. We sampled corals from six different sites approximately, 500-1000 m off shore, 10 15m depth. Six samples were collected from four sites adjacent to areas of underwater marine dredging (project sites), while the remaining two samples were obtained far away from the influence of the marine dredging (control sites). SSTs around collection time ranged 0.6-0.9 degrees C over the 40-year monthly mean. All specimens collected at project sites exhibited histopathological evidence of mild to moderate sedimentation stress including changes in size and number of mucocytes in epidermis and gastrodermis, attenuation of the epidermal and gastrodermal tissues, presence of cellular debris, and changes in number of zooxanthellae. These findings corroborate results of laboratory-based, sand application experiments. In addition to the above-noted changes, one specimen exhibited multiple lesions consisting of unusual gastrodermal detachment with infiltration of amoebocytes into the adjacent mesoglea. Tissues surrounding detachment injuries exhibited marked to severe cellular changes. Accumulations of amoebocytes at lesion sites are seldom observed in wild corals. This response may be part of an organized reaction to injury and infection, as has been documented in sea anemones and gorgonians; however, further research is needed on the nature and role(s) of the scleractinian amoebocytes. PMID- 17350652 TI - Control of multiple sclerosis relapses with immunomodulating agents. AB - Relapses in multiple sclerosis (MS) have wide-ranging consequences for patients and should be actively controlled with an appropriate immunomodulating agent provided soon after the diagnosis of MS. Several agents with varying mechanisms of action are approved for use in treating MS. Here we take a brief look at several short- and long-term comparative trials, examining the established strengths and weaknesses of the available immunomodulators. By reviewing the existing comparisons, clinicians will better understand the factors determining when to initiate therapy with an immunomodulator and how to determine which of these treatments may best suit their patients' needs. PMID- 17350651 TI - Hierarchical disabled-1 tyrosine phosphorylation in Src family kinase activation and neurite formation. AB - There are two developmentally regulated alternatively spliced forms of Disabled-1 (Dab1) in the chick retina: an early form (Dab1-E) expressed in retinal precursor cells and a late form (Dab1-L) expressed in neuronal cells. The main difference between these two isoforms is the absence of two Src family kinase (SFK) recognition sites in Dab1-E. Both forms retain two Abl/Crk/Nck recognition sites implicated in the recruitment of SH2 domain-containing signaling proteins. One of the Dab1-L-specific SFK recognition sites, at tyrosine(Y)-198, has been shown to be phosphorylated in Reelin-stimulated neurons. Here, we use Reelin-expressing primary retinal cultures to investigate the role of the four Dab1 tyrosine phosphorylation sites on overall tyrosine phosphorylation, Dab1 phosphorylation, SFK activation and neurite formation. We show that Y198 is essential but not sufficient for maximal Dab1 phosphorylation, SFK activation and neurite formation, with Y232 and Y220 playing particularly important roles in SFK activation and neuritogenesis, and Y185 having modifying effects secondary to Y232 and Y220. Our data support a role for all four Dab1 tyrosine phosphorylation sites in mediating the spectrum of activities associated with Reelin-Dab1 signaling in neurons. PMID- 17350650 TI - Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein. AB - The ribonuclease inhibitor protein (RI) binds to members of the bovine pancreatic ribonuclease (RNase A) superfamily with an affinity in the femtomolar range. Here, we report on structural and energetic aspects of the interaction between human RI (hRI) and human pancreatic ribonuclease (RNase 1). The structure of the crystalline hRI x RNase 1 complex was determined at a resolution of 1.95 A, revealing the formation of 19 intermolecular hydrogen bonds involving 13 residues of RNase 1. In contrast, only nine such hydrogen bonds are apparent in the structure of the complex between porcine RI and RNase A. hRI, which is anionic, also appears to use its horseshoe-shaped structure to engender long-range Coulombic interactions with RNase 1, which is cationic. In accordance with the structural data, the hRI.RNase 1 complex was found to be extremely stable (t(1/2)=81 days; K(d)=2.9 x 10(-16) M). Site-directed mutagenesis experiments enabled the identification of two cationic residues in RNase 1, Arg39 and Arg91, that are especially important for both the formation and stability of the complex, and are thus termed "electrostatic targeting residues". Disturbing the electrostatic attraction between hRI and RNase 1 yielded a variant of RNase 1 that maintained ribonucleolytic activity and conformational stability but had a 2.8 x 10(3)-fold lower association rate for complex formation and 5.9 x 10(9) fold lower affinity for hRI. This variant of RNase 1, which exhibits the largest decrease in RI affinity of any engineered ribonuclease, is also toxic to human erythroleukemia cells. Together, these results provide new insight into an unusual and important protein-protein interaction, and could expedite the development of human ribonucleases as chemotherapeutic agents. PMID- 17350653 TI - Studying genetic regulatory networks at the molecular level: delayed reaction stochastic models. AB - Current advances in molecular biology enable us to access the rapidly increasing body of genetic information. It is still challenging to model gene systems at the molecular level. Here, we propose two types of reaction kinetic models for constructing genetic networks. Time delays involved in transcription and translation are explicitly considered to explore the effects of delays, which may be significant in genetic networks featured with feedback loops. One type of model is based on delayed effective reactions, each reaction modeling a biochemical process like transcription without involving intermediate reactions. The other is based on delayed virtual reactions, each reaction being converted from a mathematical function to model a biochemical function like gene inhibition. The latter stochastic models are derived from the corresponding mean field models. The former ones are composed of single gene expression modules. We thus design a model of gene expression. This model is verified by our simulations using a delayed stochastic simulation algorithm, which accurately reproduces the stochastic kinetics in a recent experimental study. Various simplified versions of the model are given and evaluated. We then use the two methods to study the genetic toggle switch and the repressilator. We define the "on" and "off" states of genes and extract a binary code from the stochastic time series. The binary code can be described by the corresponding Boolean network models in certain conditions. We discuss these conditions, suggesting a method to connect Boolean models, mean-field models, and stochastic chemical models. PMID- 17350654 TI - Fairness evolution in the ultimatum game is a function of reward size. AB - I formulate a simple model of the ultimatum game, in which a proposer and a responder can receive a reward if they agree on how to divide this reward between them. The model is easy to analyse and shows that strong tendencies to fair division are expected when evolution of strategy frequencies follow the traditional gradient dynamics assumed in evolutionary models. The mean stable offer is typically around 20-40% although this depends on the maximum payoff and if rejection thresholds can evolve independently from proposals. The stable proportion offered at evolutionary equilibrium increases with the maximum payoff, if proposal and acceptance thresholds are dictated by the same strategy and cannot evolve independently. If proposal and acceptance evolve independently, the stable proportion instead decreases with the maximum payoff. The stable outcome may also show substantial variation. PMID- 17350655 TI - The Chd family of chromatin remodelers. AB - Chromatin remodeling enzymes contribute to the dynamic changes that occur in chromatin structure during cellular processes such as transcription, recombination, repair, and replication. Members of the chromodomain helicase DNA binding (Chd) family of enzymes belong to the SNF2 superfamily of ATP-dependent chromatin remodelers. The Chd proteins are distinguished by the presence of two N terminal chromodomains that function as interaction surfaces for a variety of chromatin components. Genetic, biochemical, and structural studies demonstrate that Chd proteins are important regulators of transcription and play critical roles during developmental processes. Numerous Chd proteins are also implicated in human disease. PMID- 17350656 TI - Signal pathways coupled to activation of neuronal nitric oxide synthase in the spinal cord by nociceptin/orphanin FQ. AB - Nociceptin/orphanin FQ (N/OFQ) was earlier shown to be involved in the maintenance of neuropathic pain by activating neuronal nitric oxide synthase (nNOS). We recently established an ex vivo system to elucidate biochemical and molecular mechanisms for nNOS activation by the use of a combination of isolated intact spinal cord preparations and NADPH-diaphorase histochemistry. Here we examined the N/OFQ signal pathways coupled to nNOS activation in the spinal cord by using this ex vivo system. N/OFQ enhanced nNOS activity in the superficial layer of the spinal cord, as assessed by NADPH-diaphorase histochemistry, in a time- and dose-dependent manner. The maximum effect was observed at 3-10 nM. The N/OFQ-stimulated nNOS activity was inhibited by NMDA receptor antagonists MK-801 and D-AP5, but not by the NR2B-selective antagonist CP-101,606; and the stimulated activity was observed in NR2D(-/-) mice, but not in NR2A(-/-) or NR2A( /-)/NR2D(-/-) mice. N/OFQ receptor antagonists attenuated the nNOS activity stimulated by N/OFQ, but not that by NMDA. Furthermore, the potentiation of nNOS by N/OFQ was inhibited by calphostin C and Ro 31-8220, PP2, and KN-62, but not by H-89. These results suggest that N/OFQ stimulated nNOS activity by a biochemical cascade initiated by activation of NMDA receptors containing NR2A. PMID- 17350657 TI - Antiproliferative and antioxidant activities of a tricin acylated glycoside from sugarcane (Saccharum officinarum) juice. AB - From sugarcane juice, a flavone, identified by spectroscopic methods as tricin-7 O-beta-(6''-methoxycinnamic)-glucoside, was isolated, in addition to orientin. The tricin derivative was shown to have antioxidant activity higher than Trolox by means of the DPPH assay and lower by the beta-carotene/linoleic acid system. It showed in vitro antiproliferative activity against several human cancer cell lines, with higher selectivity toward cells of the breast resistant NIC/ADR line. PMID- 17350658 TI - Strobilols A-D: four cadinane-type sesquiterpenes from the edible mushroom Strobilurus ohshimae. AB - Four sesquiterpenoids--strobilols A (1), B (2), C (3), and D (4)--were isolated from the organic extracts of fruiting bodies of the edible mushroom Strobilurus ohshimae. Their structures were determined by spectroscopic methods. Compound 1 exhibited moderate activity against the brine shrimp Artemia salina. This paper is the first report on isolation of cadinane-type sesquiterpenoids from S. ohshimae. PMID- 17350659 TI - Isolation and identification of potential cancer chemopreventive agents from methanolic extracts of green onion (Allium cepa). AB - Phase II xenobiotic metabolizing enzymes confer amelioration of risk arising from potentially carcinogenic chemicals derived both endogenously, and exogenously, from food and the environment. In this study, efforts were made to isolate and identify potentially cancer preventive constituents from methanolic extracts of green onion (Allium cepa) directed by the quinone reductase (QR) induction bioassay using murine hepatoma (Hepa 1c1c7) cells. Crude methanolic extracts of green onion tissue were solvent-partitioned, and subsequently fractionated by flash chromatography, thin layer chromatography and high pressure preparative liquid chromatography to afford pure QR-inducing isolates. Multiple isolates were found active at inducing QR. One newly identified compound, 5-hydroxy-3-methyl-4 propylsulfanyl-5H-furan-2-one (3), and four known compounds: 5-(hydroxymethyl) furfural (1), acetovanillone (2), methyl 4-hydroxyl cinnamate (4) and ferulic acid methyl ester (5), were isolated and identified as active agents. PMID- 17350660 TI - [Mandibular aggressive fibromatosis]. AB - INTRODUCTION: Aggressive fibromatosis is a rare histologically benign fibrous tumor with a potential for locoregional aggression. Treatment is not well defined and several therapeutic approaches have been proposed. Surgical treatment is the reference, chemotherapy, radiotherapy and homonotherapy being proposed as complementary treatment or for inoperable tumors. CASE REPORT: A three-year-old patient underwent surgery for removal of a mandibular tumor. Pathology reported aggressive fibromatosis. The patient was given conservative treatment and was free of recurrence nine years after resection. DISCUSSION: Conservative surgery for aggressive mandibular fibromatosis appears to be preferable to radical mutilating surgery which would have a major impact on facial growth in children. PMID- 17350661 TI - Spatial patterns and coexistence mechanisms in systems with unidirectional flow. AB - River ecosystems are the prime example of environments where unidirectional flow influences the dispersal of individuals. Spatial patterns of community composition and species replacement emerge from complex interplays of hydrological, geochemical, biological, and ecological factors. Local processes affecting algal dynamics are well understood, but a mechanistic basis for large scale emerging patterns is lacking. To understand how these patterns could emerge in rivers, we analyze a reaction-advection-diffusion model for two competitors in heterogeneous environments. The model supports waves that invade upstream up to a well-defined "upstream invasion limit". We discuss how these waves are produced and present their key properties. We suggest that patterns of species replacement and coexistence along spatial axes reflect stalled waves, produced from diffusion, advection, and species interactions. Emergent spatial scales are plausible given parameter estimates for periphyton. Our results apply to other systems with unidirectional flow such as prevailing winds or climate-change scenarios. PMID- 17350662 TI - Tissue- and cell-specific expression of metallothionein genes in cadmium- and copper-exposed mussels analyzed by in situ hybridization and RT-PCR. AB - Metallothioneins (MTs) are metal-inducible proteins that can be used as biomarkers of metal exposure. In mussels two families of MT isoforms (MT10 and MT20) have been characterized. In this study, mussels (Mytilus galloprovincialis) were exposed to 200 ppb Cd and 40 ppb Cu for 2 and 9 days to characterize the tissue and isoform specificity of metal-induced MT expression. Non-radioactive in situ hybridization demonstrated that both MT isoforms were mainly transcribed in digestive tubule epithelial cells, especially in basophilic cells. Weaker MT expression was detected in non-ciliated duct cells, stomach and gill epithelial cells, haemocytes, adipogranular cells, spermatic follicles and oocytes. RT-PCR resulted in cloning of a novel M. galloprovincialis isoform homologous to recently cloned Mytilus edulis intron-less MT10B isoform. In gills, Cd only affected MT10 gene expression after 2 days of exposure while increases in MT protein levels occurred at day 9. In the digestive gland, a marked increase of both isoforms, but especially of MT20, was accompanied by increased levels of MT proteins and basophilic cell volume density (Vv(BAS)) after 2 and 9 days and of intralysosomal metal accumulation in digestive cells after 9 days. Conversely, although metal was accumulated in digestive cells lysosomes and the Vv(BAS) increased in Cu-exposed mussels, Cu exposure did not produce an increase of MT gene expression or MT protein levels. These data suggest that MTs are expressed in a tissue-, cell- and isoform-specific way in response to different metals. PMID- 17350663 TI - Cytotoxicity of SiO2 in A549 cells. PMID- 17350664 TI - Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis. AB - Methamphetamine (METH) is an abused drug that may cause psychiatric and neurotoxic damage, including degeneration of monoaminergic terminals and apoptosis of non-monoaminergic cells in the brain. The cellular and molecular mechanisms underlying these METH-induced neurotoxic effects remain to be clarified. In this study, we performed a time course assessment to investigate the effects of METH on intracellular oxidative stress and mitochondrial alterations in a human dopaminergic neuroblastoma SH-SY5Y cell line. We characterized that METH induces a temporal sequence of several cellular events including, firstly, a decrease in mitochondrial membrane potential within 1 h of the METH treatment, secondly, an extensive decline in mitochondrial membrane potential and increase in the level of reactive oxygen species (ROS) after 8 h of the treatment, thirdly, an increase in mitochondrial mass after the drug treatment for 24 h, and finally, a decrease in mtDNA copy number and mitochondrial proteins per mitochondrion as well as the occurrence of apoptosis after 48 h of the treatment. Importantly, vitamin E attenuated the METH-induced increases in intracellular ROS level and mitochondrial mass, and prevented METH induced cell death. Our observations suggest that enhanced oxidative stress and aberrant mitochondrial biogenesis may play critical roles in METH-induced neurotoxic effects. PMID- 17350665 TI - Time and pH-dependent sorption of the veterinary antimicrobial sulfathiazole to clay minerals and ferrihydrite. AB - Substantial amounts of sulfonamides, ionizable, polar veterinary antimicrobials, may reach the environment by spreading of manure. Sorption to soils and sediments is a crucial but not sufficiently understood process influencing the environmental fate of sulfonamides. Therefore, we investigated sorption of sulfathiazole to clay minerals (montmorillonite, illite) and ferrihydrite for varying pH values and two contact times (1d, 14 d) under sterile conditions. Results were compared to sulfathiazole sorption to organic sorbents. Sulfathiazole sorption to inorganic sorbents exhibited pronounced pH dependence consistent with sorbate speciation and sorbent charge properties. While sulfathiazole cations were most important for sorption to clay minerals, followed by neutral species, ferrihydrite was a specific anion sorbent, showing significant sorption only between pH 5.5-7. Experiments revealed a substantial increase of sorption with time for ferrihydrite (pH 5.5-7) and illite (pH<5.5). Reasons may be disaggregation of clay minerals and, for ferrihydrite, diffusion and sorption of sulfathiazole in micropores. Independent of contact time and pH, sorption to inorganic sorbents was more than an order of magnitude lower than to organic sorbents. This implies that in many topsoils and sediments inorganic sorbents play a minor role. Our results highlight the need to account for contact time and speciation when predicting sulfonamide sorption in the environment. PMID- 17350666 TI - Dioxins, metals, and fish toxicity in ash residue from space heaters burning used motor oil. AB - Ash residue, generated from burning used motor oil, is a complex and ubiquitous waste stream. Ash samples were collected from space heaters and analyzed for dioxins (N=10), expressed as toxic equivalents (TEQ), and heavy metals (N=9). TEQ averaged 148-164 ng kg(-1) (standard deviation [SD] 385-416 ng kg(-1)), depending on methods used for non-detects (NDs) and toxic equivalency factors (TEFs). It is notable that median TEQ (2.89-3.49 ng kg(-1)) was about 50 fold lower, reflecting the influence of several high end values on the mean. The proportion of NDs among 17 polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in each sample averaged 38.2% (range 0-94.1%). Total metals averaged 103,000 mg kg(-1) (SD 26,600 mg kg(-1)), with Zn, Cu, and Pb contributing 89.3%, 6.4%, and 3.0% of the total, respectively. Rainbow trout bioassays resulted in median mortalities of 3.2% and 42.0% (respective SD 25.3% and 43.2%) at ash concentrations of 10 and 100 mg l(-1), respectively. Nominal concentrations of several metals (e.g., Cu, Zn) in the fish bioassay exceeded their reported median lethal concentrations (LC50s) for the test species. Multiple regressions (Bonferroni P<0.05) demonstrated that most of the variance in fish mortality could be accounted for by pH, metals (e.g., As, Cd, Pb), and TEQ. Mean TEQ concentration in used oil ash ranked on the high end of TEQ content in other environmental matrices, including wood ash, cement kiln dust, biosolids, and soils. Overall, these results suggest that suitable disposal methods are needed for ash generated from burning used motor oil. PMID- 17350667 TI - Pulmonary thromboendarterectomy: a clinicopathologic study of 200 consecutive pulmonary thromboendarterectomy cases in one institution. AB - Approximately 2000 patients underwent pulmonary thromboendarterectomy (PTE) to date at University of California, San Diego. We retrospectively reviewed the clinicopathologic manifestations of 200 consecutive PTE cases from June 2004 to February 2006 with an emphasis on the histopathologic spectrum of chronic thromboembolic disease. Pathology reports and all histologic sections of study cases were examined. Pertinent clinical data were obtained from operative reports and medical records. In the study group, there were 2 cases (1 man, 1 woman) of pulmonary artery sarcomas and 1 case of metastatic tumor emboli from a testicular germ cell tumor. Two patients (both women) showed histologic evidence of arteritis without clinically apparent systemic vasculitis. The remaining 195 PTE patients with chronic thromboembolic disease consisted of 97 women and 98 men with a mean age of 52 (range, 17-83) and 51 (range, 16-82), respectively. Bilateral PTE was performed in 191, and unilateral PTE was performed in 4 (right and left, 2 each) patients. History of deep vein thrombosis was noted in 38.5%, and coagulation abnormalities were documented in 16.4% of these 195 cases. Grossly, the volumes of PTE specimens were greater in men than in women and on the right side than on the left in both men and women. Microscopically, the thrombi were recent fibrinous clot in 0.8%, mixed fibrinous and organizing in 45%, and old organized in 54.2% of specimens. Inflammation within the thrombi was usually mild but moderate and severe inflammation was found in 13.4% and 1.3% of specimens, respectively. Exuberant epithelioid granulomas were seen within the thrombi in one patient who had a history of sarcoidosis. Collections of foamy histiocytes and/or cholesterol clefts were found in 45%, and calcification was present in 11.5% of specimens. One case revealed diffuse myofibroblastic proliferation in a highly inflammatory background containing numerous plasma cells, reminiscent of inflammatory myofibroblastic tumor. In summary, pathology of PTE specimens in our study group encompassed remodeling of thrombi at various stages with variable degrees of inflammation and cellularity, granulomas associated with sarcoidosis, a rare case showing features of inflammatory myofibroblastic tumor, primary or metastatic malignancy, and isolated pulmonary arteritis. PMID- 17350668 TI - Utility of SKP2 and MIB-1 in grading follicular lymphoma using quantitative imaging analysis. AB - Follicular lymphoma is classified into grades (G)1, 2, and 3 based on the number of centroblasts in neoplastic follicles. However, the accuracy of manually counting these centroblasts is limited by certain cells (large centrocytes, follicular dendritic cells, and histiocytes) that could mimic centroblast morphology. The reproducibility of follicular lymphoma grading is dependent upon observer experience; therefore, significant variations occur. This study is to explore a more objective, reliable way of grading follicular lymphoma using a quantitative imaging system in conjunction with immunostains with antibodies to proliferation markers MIB-1 and S-phase kinase-associated protein 2 (SKP2). Fifty eight follicular lymphomas (G1, n = 23; G2, n = 18; and G3, n = 17) were studied on formalin-fixed, paraffin-embedded sections. Positive nuclear staining of both Ki-67 and SKP2 was recorded using the quantitative Clarient ACIS II system (Aliso Viejo, CA, USA). Ten high-power fields (x400) from randomly selected neoplastic follicles were counted by a pathologist blinded to the previously assigned morphologic grade. The results show that the percentages of Ki-67+ and SKP2+ cells significantly differ among the different grades of follicular lymphoma. A higher grade of follicular lymphoma is associated with a higher percentage of Ki 67+ and SKP2+ cells. The overall SKP2+% cells are substantially lower than Ki 67+% cells in the same grade of follicular lymphoma. Statistical significance is observed in Ki-67+ cells between follicular lymphoma G1 and follicular lymphoma G3 and between G1 and G2. In contrast, statistical significance is noted in SKP2+% cells between follicular lymphoma G1 and follicular lymphoma G3 and between follicular lymphoma G2 and follicular lymphoma G3. The findings suggest that the SKP2 expression has better discrimination with grades of follicular lymphoma than Ki-67 expression. Compared with traditional methods, quantitation of SKP2 expression using a quantitative image analysis system might be a useful and objective approach in grading follicular lymphoma. PMID- 17350669 TI - Fatty acid synthase overexpression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype. AB - Overexpression of fatty acid synthase (FASN), a key enzyme for de novo lipogenesis, is observed in many cancers including colorectal cancer and is associated with poor clinical outcomes. Cellular FASN expression is physiologically upregulated in a state of energy excess. Obesity and excess energy balance have been known to be risk factors for colorectal cancer. High degree of microsatellite instability (MSI-H) is a distinct phenotype in colorectal cancer, associated with CpG island methylator phenotype (CIMP). Previous data suggest that obesity or altered energy balance may potentially modify risks for MSI-H cancers and microsatellite stable (MSS) cancers differently. However, the relationship between MSI and FASN overexpression has not been investigated. Using 976 cases of population-based colorectal cancer samples from 2 large prospective cohort studies, we correlated FASN expression (by immunohistochemistry) with MSI, KRAS and BRAF mutations, p53 expression (by immunohistochemistry), and CIMP status [determined by MethyLight for 8 CIMP specific gene promoters including CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1]. Marked (2+) FASN overexpression was observed in 110 (11%) of the 976 tumors and was significantly more common in MSI-H tumors (21% [28/135]) than MSI-low (5.6% [4/72], P = .004) and MSS tumors (11% [72/678], P = .001). The association between FASN overexpression and MSI-H persisted even after stratification by CIMP status. In contrast, FASN overexpression was not correlated with CIMP after stratification by MSI status. Fatty acid synthase overexpression was not significantly correlated with sex, tumor location, p53, or KRAS/BRAF status. In conclusion, FASN overexpression in colorectal cancer is associated with MSI-H, independent of CIMP status. PMID- 17350670 TI - Immunohistochemical detection of antiapoptotic protein X-linked inhibitor of apoptosis in mammary carcinoma. AB - An immunohistochemical survey of X-linked inhibitor of apoptosis (XIAP) expression in mammary carcinoma was performed. XIAP, the most potent of the inhibitor of apoptosis family of caspase inhibitors, has been linked to tumor aggressiveness and therapeutic resistance in several malignancies and is considered an attractive target for cancer drug discovery. Routinely processed sections from 94 ductal carcinomas, 9 lobular carcinomas, and 10 ductal carcinomas with lobular components or features were subjected to citrate-based antigen retrieval, immunostained with anti-XIAP (BD Biosciences, Franklin Lakes, NJ), Envision+ reagents (Dako, Carpinteria, CA), and diaminobenzidine. Positive staining was found in 22.7% of grade 1, 44% of grade 2, and 89.5% of grade 3 ductal carcinomas. Strong staining occurred in no cases of grade 1, 13% of grade 2, and 55.2% of grade 3 ductal carcinomas. XIAP staining increased overall with grade of ductal carcinoma in situ as well. The staining intensity of invasive carcinoma correlated with that of the corresponding ductal carcinoma in situ in 70% of cases. Ductal carcinomas overall showed more staining than lobular carcinomas. XIAP is most strongly and commonly detected in grade 3 ductal carcinoma. The degree of XIAP expression appears frequently to be determined in the preinvasive intraductal phase of tumorigenesis. These findings suggest a possible role of XIAP in the more aggressive clinical behavior of grade 3, compared with lower-grade ductal carcinomas. PMID- 17350671 TI - Age-related changes of astorocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector. AB - We investigated the age-related alterations of astorocyte, oligodendrocyte and microglia in the mouse hippocampal CA1 sector under the same conditions using immunohistochemistry. Glial fibrillary acidic protein (GFAP), 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and isolectin B(4) immunoreactivity was measured in 2-, 8-, 18-, 40-42- and 50-59-week-old mice. Total number of GFAP positive cells was unchanged in the hippocampal CA1 sector up to 40-42 weeks of birth. In 50-59-week-old mice, however, a significant increase in the number of GFAP-positive cells was observed in the hippocampal CA1 sector, exhibiting the morphology of reactive astrocytes. In contrast, the fibers of CNPase immunoreactivity were unchanged in the hippocampal CA1 sector up to 18 weeks of birth. In 40-42- and 50-59-week-old mice, however, a significant decrease in the densities of CNPase-positive fibers was observed in the hippocampal CA1 sector. On the other hand, total number of isolectin B(4)-positive cells was unchanged in the hippocampal CA1 sector up to 40-42 weeks of birth. In 50-59-week-old mice, however, a significant decrease in the number of isolectin B(4)-positive cells was observed in the hippocampal CA1 sector. Our results show that astrocytes proliferate and are activated in the hippocampal CA1 sector with advancing age. Furthermore, the present study demonstrates that the fibers of oligodendrocytes and total number of microglial cells in the hippocampal CA1 sector are decreased during ageing processes. These results suggest that age-related changes of astorocytes, oligodendrocytes and microglia had occurred in the mouse hippocampal CA1 sector. PMID- 17350672 TI - On an empirical relationship between SO2 concentration and distance from a highway using passive samplers: a case study in Shanghai, China. AB - In this paper, field measurements were performed to determine SO(2) concentration gradients from a highway in Shanghai using passive samplers. It was demonstrated that passive sampling method is a cost-effective and convenient way to monitor specific gaseous pollutants at small scales over long sampling periods in air quality studies. Using function fit analysis for the measured results, a shifted power-law relationship had been found between SO(2) concentration and the distance from a highway. Accordingly, an empirical shifted power-law model was developed for describing and predicting the SO(2) gradients near a highway, in which k is the only parameter and named as diffusion attenuation coefficient. There was a surprisingly significant negative correlation between known SO(2) concentration at reference point (C(0)) and diffusion attenuation coefficient (k). By the correlation equation of C(0) and k, appropriate value of k could be calculated with measured C(0). Therefore, the empirical shifted power-law model developed in this study could be practically and conveniently applied for predicting the SO(2) distributions near a highway with known C(0). PMID- 17350673 TI - True difference or something else? Problems in cost of osteoarthritis studies. AB - OBJECTIVES: To identify the commonalities and discrepancies among the published cost of osteoarthritis (OA) studies and to further propose some potential improvements for this type of research. METHODS: A systematic literature review was performed on MEDLINE (1966 to April 2006) by using 2 overlapping search strategies to identify cost of illness studies in OA based on the predefined eligible criteria. Direct and indirect costs per patient per annum were separately summarized across studies and countries. The sample size-weighted mean was calculated when there were 2 or more studies from the same country. Discount rates of 3% and appropriate exchange rates were used in conversion of the costs reported in different years and different currencies to 2005 US dollars. RESULTS: Ten articles fulfilling the eligible criteria were included in the literature synthesis. Of these, 4 were from the USA, 2 each from Canada and France, and 1 each from Italy and Hong Kong. After adjusted to 2005 US dollars, annual direct costs per patient (in descending order) were $9147 in Hong Kong, $4792 in USA, $2878 in Canada, $1271 in Italy, and $345 in France. In contrast, indirect costs were only reported by 5 studies in 4 countries. The highest indirect costs were $9847 per patient per annum in Canada and the lowest were $864 in Hong Kong. CONCLUSIONS: The observed substantial variations in costs of OA across studies and countries may not reflect the true differences among them. The comparability across these identified studies is quite limited, which highlights the importance of standardization in cost of OA studies. PMID- 17350674 TI - Epidemiology of spondyloarthritis in the People's Republic of China: review of the literature and commentary. AB - OBJECTIVES: The prevalence of spondyloarthritis (SpA) and its prototype ankylosing spondylitis (AS) varies considerably in different parts of the world. With 20% of the world's population in China, there is potential for a significant disease burden. Eight of the 10 articles providing primary data on the prevalence of SpA in China are in the Chinese language; our objective is to review all 10 articles for English readers. METHODS: Articles were retrieved by search engines in both the English language (www.pubmed.gov) and Chinese language web sites (www.cnki.net). We limited our search to publications of the period 1994 to 2006, and the key words used were (entered as Chinese characters) "prevalence AND spondyloarthropathy," "prevalence AND ankylosing spondylitis," "epidemiology AND spondyloarthropathy," and "epidemiology AND ankylosing spondylitis." For each survey, we examined the number of subjects surveyed, the survey instrument, the criteria used for classifying patients as SpA or AS, and other methodological quality issues. RESULTS: There were 2 AS surveys in the military and 8 surveys in the civilian communities. Overall, the pooled prevalence of AS for the military and civilian communities is 0.24%, 95% confidence interval (CI: 0.17 to 0.32) and 0.23%, 95% CI (0.19 to 0.28), respectively. There is 1 SpA survey in the military and 4 surveys in the civilian communities. The prevalence of SpA in the military survey is 0.45%. The pooled prevalence of SpA from the civilian surveys is 0.93%, 95%CI (0.53 to 1.65). We found that the survey methodology is generally not well reported, giving rise to concerns about the methodological quality and hence validity of the results. CONCLUSION: The prevalence of AS and SpA in China are similar to Caucasians in the U.S. or Europe. PMID- 17350675 TI - Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes. AB - OBJECTIVES: To discuss fibromyalgia syndrome (FMS) and overlapping conditions, eg, irritable bowel syndrome, headaches, and chronic fatigue syndrome, within the concept of central sensitivity syndromes (CSS). METHODS: A critical overview of the literature and incorporation of the author's own views. RESULTS: The concept of CSS seems viable. It is based on mutual associations among the CSS conditions as well as the evidence for central sensitization (CS) among several CSS members. However, such evidence is weak or not available in other members at this time, requiring further studies. The biology of CSS is based on neuroendocrine aberrations, including CS, that interact with psychosocial factors to cause a number of symptoms. CONCLUSIONS: CSS is an important new concept that embraces the biopsychosocial model of disease. Further critical studies are warranted to fully test this concept. However, it seems to have important significance for new directions for research and patient care involving physician and patient education. Each patient, irrespective of diagnosis, should be treated as an individual considering both the biological and psychosocial contributions to his or her symptoms and suffering. PMID- 17350676 TI - Varied presentations of enthesopathy. AB - BACKGROUND: The concept of "enthesis organ" allows a new look at the nature of enthesis involvement in some rheumatic and nonrheumatic systemic disorders. OBJECTIVES: To describe the various presentations of enthesopathy in the course of systemic medical disorders using the available literature data. METHODS: Review of relevant articles from 1996 to 2006 retrieved by a Medline search utilizing the index terms "enthesis," "enthesitis," and "tendonitis." The list of articles reviewed herein is not exhaustive, with preference given, where possible, to studies and surveys over case reports as well as the most recent literature reflecting new developments on the subject. RESULTS: Enthesis is defined as the site of insertion of a tendon, ligament, fascia, or articular capsule into bone. Pain originating in the free nerve endings enriched entheses (enthesalgia) may represent a potential cause of chronic musculoskeletal pain in some individuals. Enthesis involvement in the disease process is well appreciated in spondyloarthropathies and in rheumatoid arthritis, though overshadowed by synovitis in the latter. Calcium deposition diseases may constitute the most significant articular cause of enthesopathies in the general population. New data may shed light on the possible pathophysiologic role of enthesopathy in the development of osteoarthritis. Various metabolic and endocrine conditions may manifest with enthesopathy features. The pathogenic mechanisms of enthesis involvement are not uniform and differ in the diverse disorders. CONCLUSIONS: The concept of enthesopathy as a variety of syndromes in the course of many rheumatic, metabolic, and endocrine disorders should be appreciated. Exercise of a high level of suspicion toward enthesopathic involvement, and greater knowledge of enthesopathy's characteristic patterns and diagnostic possibilities, may allow better management of many patients in rheumatology practice. PMID- 17350677 TI - Alginate as an antiglycating agent for human serum albumin. AB - Hyperglycemia and the accumulation of advanced glycation endproducts (AGEs) in tissues and serum have important roles in diabetic complications. Therefore, the identification of anti-glycation compounds is attracting considerable interest. In this study, the interaction of human serum albumin (HSA) with fructose, in the absence and presence of alginate, was studied by circular dichroism, absorbance and fluorescence techniques. The characterization study of AGEs was performed using autofluorescence, fibrillar formation, the increase in absorbance and the quantification of free lysine side chains. The results indicate that alginate inhibits the fructation of HSA as observed by a reduction in the formation of fluorescent AGEs and fibrils. Furthermore, alginate reduces the amount of modified lysine side chains, signified by the lack of increase in absorbance, and increases the helicity of this protein. PMID- 17350678 TI - Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from a heparin-conjugated poly(L-lactic-co-glycolic acid) scaffold. AB - In this study, a heparin-conjugated poly(l-lactic-co-glycolic acid) (HP-PLGA) scaffold was developed for the sustained delivery of bone morphogenetic protein-2 (BMP-2), and then used to address the hypothesis that BMP-2 delivered from this scaffold could enhance ectopic bone formation. We found the amount of heparin conjugated to the PLGA scaffolds could be increased up to 3.2-fold by using scaffolds made from star-shaped PLGA, as compared to scaffolds made from linear PLGA, and that the release of BMP-2 from the HP-PLGA scaffold was sustained for at least 14 days in vitro. The BMP-2 released from the HP-PLGA scaffold stimulated an increase in alkaline phosphatase (ALP) activity of osteoblasts for 14 days in vitro, suggesting that the HP-PLGA scaffold delivery system releases BMP-2 in a bioactive form for a prolonged period. By contrast, BMP-2 release from unmodified (no heparin) PLGA scaffolds induced a transient increase in ALP activity for the first 3 days and a decrease thereafter. In vivo bone formation studies showed the BMP-2-loaded HP-PLGA scaffolds induced bone formation to a much greater extent than did either BMP-2-loaded unmodified PLGA scaffolds or unloaded (no BMP-2) HP-PLGA scaffolds, with 9-fold greater bone formation area and 4-fold greater calcium content in the BMP-2-loaded HP-PLGA scaffold group compared to the BMP-2-loaded unmodified PLGA scaffold group. Collectively, these results demonstrate that the HP-PLGA delivery system is capable of potentiating the osteogenic efficacy of BMP-2, and underscore its importance as a possible bone regeneration strategy. PMID- 17350679 TI - Comparative aspects of placental evolution: a workshop report. PMID- 17350680 TI - TRPC1: the link between functionally distinct store-operated calcium channels. AB - Although store-operated calcium entry (SOCE) was identified more that two decades ago, understanding the molecular mechanisms that regulate and mediate this process continue to pose a major challenge to investigators in this field. Thus, there has been major focus on determining which of the models proposed for this mechanism is valid and conclusively establishing the components of the store operated calcium (SOC) channel(s). The transient receptor potential canonical (TRPC) proteins have been suggested as candidate components of the elusive store operated Ca(2+) entry channel. While all TRPCs are activated in response to agonist-stimulated phosphatidylinositol 4,5, bisphosphate (PIP(2)) hydrolysis, only some display store-dependent regulation. TRPC1 is currently the strongest candidate component of SOC and is shown to contribute to SOCE in many cell types. Heteromeric interactions of TRPC1 with other TRPCs generate diverse SOC channels. Recent studies have revealed novel components of SOCE, namely the stromal interacting molecule (STIM) and Orai proteins. While STIM1 has been suggested to be the ER-Ca(2+) sensor protein relaying the signal to the plasma membrane for activation of SOCE, Orai1 is reported to be the pore-forming component of CRAC channel that mediates SOCE in T-lymphocytes and other hematopoetic cells. Several studies now demonstrate that TRPC1 also associates with STIM1 suggesting that SOC and CRAC channels are regulated by similar molecular components. Interestingly, TRPC1 is also associated with Orai1 and a TRPC1-Orai1-STIM1 ternary complex contributes to SOC channel function. This review will focus on the diverse SOC channels formed by TRPC1 and the suggestion that TRPC1 might serve as a molecular link that determines their regulation by store-depletion. PMID- 17350681 TI - Central AT(1) receptor blockade increases metabolic cost during exercise reducing mechanical efficiency and running performance in rats. AB - The effect of central angiotensin AT(1) receptor blockade on metabolic rate and running performance in rats during exercise on a treadmill (18 m x min(-1), 5% inclination) was investigated. Oxygen consumption (VO(2)) was measured, using the indirect calorimetry system, while the animals were exercising until fatigue after injection of 2 microL of losartan (Los; 60 nmol, n=9), an angiotensin II AT(1) receptor antagonist, or 2 microL of 0.15 M NaCl (Sal, n=9) into the right lateral cerebral ventricle. Mechanical efficiency (ME) and workload (W) were calculated. The W performance by Los-treated animals was 29% lesser than in Sal treated animals (p<0.02). During the first 10 min of exercise (dynamic state of exercise), there was a similar increase in VO(2), while ME remained the same in both groups. Thereafter (steady state of exercise), VO(2) remained stable in the Sal group but continued to increase and stabilized at a higher level in Los treated animals until fatigue. During the steady state of exercise there was a sharper reduction in ME in Los-treated rats compared to Sal-treated animals (p<0.01) that was closely correlated to W (r=0.74; p<0.01). Our data showed that AT(1) receptor blockade increases metabolic cost during exercise, reducing mechanical efficiency. These results indicate that central angiotensinergic transmission modulates heat production, improving ME during the steady state of exercise. PMID- 17350682 TI - Characteristics of novel myeloid precursor cell line, PC-MDS, established from a bone marrow of the patient with therapy-related myelodysplastic syndrome. AB - We report on characteristics of the first human cell line, PC-MDS, derived from a bone marrow of a patient with therapy-related myelodysplastic syndrome (t-MDS) who had no overt post-MDS leukemia. Classic cytology analyses, immunophenotyping, cytogenetic and molecular genetic procedures were used for characterization of the cell line. PC-MDS cells are positive for the expression of CD13, CD15, CD30, CD33, and CD45 antigen. Positive cytochemical staining and immunophenotype analyses indicated that PC-MDS cells have some characteristics of the early myeloid precursor cell. The karyotype analysis of PC-MDS cell line revealed various numerical and structural changes including those typically associated with t-MDS: del(5)(q13)[7], der(5)t(5;11)(p11;q11)[13], -7[6], del(7)(q31)[2], +20[3], -20[4]. Evaluation of methylation status in a promoter region of p15, p16 and MGMT genes showed biallelic hypermethylation pattern of 5' promoter region only in MGMT gene. PC-MDS is the first t-MDS derived cell line, and based on its immunological, cytogenetic and molecular characterization could be a new tool in evaluation of complex biology of MDS and a model for methylation studies. PMID- 17350683 TI - Clinical significance of high-Km 5'-nucleotidase (cN-II) mRNA expression in high risk myelodysplastic syndrome. AB - We analyzed cytosolic high-Km 5'-nucleotidase (cN-II) and deoxycytidine kinase (dCK) mRNA expression in bone marrow mononuclear cells (BMMNC) of patients with high-risk myelodysplastic syndrome (MDS) using quantitative real-time polymerase chain reaction (rt-PCR). At diagnosis, the cN-II mRNA expression of patients was higher than that of healthy volunteers, but the dCK mRNA expression showed no significant difference. Patients with ara-C-containing chemotherapies whose BMMNC showed a high level of cN-II expression (greater than the median value) had shorter median overall survival (15 months versus 22 months, p<0.01) and shorter median post-chemotherapy survival (10 months versus 16 months, p=0.012). These data suggest that the expression level of cN-II mRNA might be a prognostic factor of high-risk MDS. PMID- 17350684 TI - No effect of platelet-activating factor on the proliferation and apoptosis of immature forms of leukemic blasts. PMID- 17350685 TI - Multigeneration effects of insect growth regulators on the springtail Folsomia candida. AB - Multigeneration tests are very useful for the assessment of long term toxicity of pollutants such as endocrine disruptor compounds. In this study, multigeneration reproduction tests adapted from the ISO standard 11267 were conducted with the Collembola Folsomia candida. Springtails were exposed to artificial soil contaminated with four insect growth regulators (methoprene, fenoxycarb, teflubenzuron, and precocene II) according to two different experimental set-ups. In the first set-up, the parental generation (F(0)) of Collembola was exposed to a pollutant for 28 days. Juveniles from the F(1) generation were transferred to uncontaminated soil for another 28-day period to generate the F(2) generation. In the second set-up, the F(0) generation was exposed to a pollutant for 10 days before being transferred to uncontaminated soil to reproduce. After 18-28 days, juveniles from the F(1) were transferred to clean soil to generate the F(2) generation. An effect on the number of hatched juveniles of the F(2) generation was observed for methoprene after exposure of the F(0) for 28 days and hatching of F(1) in contaminated soil. For methoprene and teflubenzuron, significant effects were even observed on the F(2) generation with the second experimental set-up, when only the F(0) generation was exposed for 10 days. This shows that the impact of these substances is transgenerational, which can have important consequences for the population of these or other organisms. No effect on the F(2) generation was observed with fenoxycarb and precocene II with the 10-day exposure experiment. Our results show that the developed experimental procedures are appropriate to assess the long term effects of endocrine disrupting compounds on the reproduction of the non-target species F. candida. Another important finding is that two substances with the same predicted mode of action (i.e., the two juvenile hormone analogues fenoxycarb and methoprene) do not necessarily affect the same endpoints in F. candida. PMID- 17350686 TI - MICA marks additional risk factors for Type 1 diabetes on extended HLA haplotypes: an association and meta-analysis. AB - The association of the HLA complex on chromosome 6 does not explain total linkage of the HLA region to Type 1 Diabetes (T1D), leading to the hypothesis that there may be additional causal genes in the HLA region for immune-related disorders. Reports on the MHC Class I chain-related A (MICA) gene as candidate for association with T1D are contradicting. We investigated whether variation in MICA is associated to T1D in a cohort of 350 unrelated individuals with juvenile-onset T1D and 540 control subjects, followed by a meta-analysis of 14 studies. We also investigated an HLA-independent association for MICA with T1D. In our case control study, we found that the MICA*A5 variant was significantly associated with an increased risk for T1D, while MICA*A6 was significantly associated with a decreased risk that was confirmed by our meta-analysis. However, the meta analysis did not show an association of MICA*A5 T1D. Analysis of MICA alleles conditional on T1D-associated high-risk MHC class II haplotypes revealed that MICA*A6 was associated with an increased risk for T1D when this marker co occurred with HLA DQ2DR17 T1D-risk-haplotypes. In contrast, MICA*A6 reduced the risk from the HLA DQ8DR4 T1D-risk haplotype. Moreover, MICA*A9 showed a significant association to increased risk for T1D on DQ8DR4 haplotypes. Co inheritance of MICA*A6 with the HLA DQ2DR17 haplotype in T1D indicates this haplotype may carry the additional genetic factors for T1D, but our study does not support an independent association between MICA variants and T1D. PMID- 17350687 TI - Clear lens extraction with multifocal apodized diffractive intraocular lens implantation. AB - PURPOSE: To assess efficacy, safety, predictability, and stability after clear lens extraction (CLE) with multifocal diffractive intraocular lens (IOL) implantation. DESIGN: Prospective, nonrandomized, masked observational case series (self-controlled). PARTICIPANTS: Two hundred twenty-four eyes of 112 consecutive patients after CLE with bilateral AcrySof ReSTOR Natural IOL implantation. Eyes were divided into myopic (mean spherical equivalent [SE], 6.01+/-2.71 diopters [D]) and hyperopic (mean SE, +3.86+/-2.52 D) groups. METHODS: Monocular and binocular uncorrected distance visual acuity (VA), best corrected distance VA, uncorrected distance near VA, and best distance-corrected near VA were recorded preoperatively and 6 months after surgery. MAIN OUTCOMES MEASURES: Efficacy, safety, predictability, and stability. RESULTS: At 6 months postoperatively, uncorrected distance VA was 20/25 or better in 100% of the eyes. Efficacy indexes were 0.97 for myopic and 0.96 for hyperopic patients. No eye lost > or =2 lines of best-corrected distance VA; for the myopic group, 10 eyes gained 1 line, and 10 eyes gained > or =2 lines; for the hyperopic group, 20 eyes gained 1 line, and 15 eyes gained > or =2 lines. Safety indexes were 1.05 for myopic and 1.02 for hyperopic patients. All eyes were within +/-1.00 D of the desired refraction. No eye lost >2 lines of best distance-corrected near VA; for the myopic group, 10 eyes lost 1 or 2 lines, 15 eyes gained 1 line, and 5 eyes gained 2 lines; for the hyperopic group, 8 eyes lost 1 or 2 lines, 20 eyes gained 1 line, and 16 eyes gained 2 lines. Safety indexes at near were 1.05 for myopic and 1.11 for hyperopic patients. Uncorrected distance near VA was better for hyperopic than myopic patients (0.95+/-0.08 vs. 0.88+/-0.15). Efficacy indexes at near were 1.03 for myopic and 1.10 for hyperopic patients. CONCLUSIONS: Clear lens extraction with multifocal IOL implantation is an effective procedure for correcting ametropia and presbyopia. Safety and efficacy indexes at distance were comparable in myopic and hyperopic patients. However, at near, both indexes were larger for hyperopic patients. PMID- 17350688 TI - Femtosecond laser versus mechanical microkeratome for LASIK: a randomized controlled study. AB - PURPOSE: To compare corneal haze (backscattered light) and visual outcomes between fellow eyes randomized to LASIK with the flap created by a femtosecond laser (bladeless) or with the flap created by a mechanical microkeratome. DESIGN: Randomized, controlled, paired-eye study. PARTICIPANTS: Twenty-one patients (42 eyes) received LASIK for myopia or myopic astigmatism. METHODS: One eye of each patient was randomized to flap creation with a femtosecond laser (IntraLase FS, IntraLase Corp., Irvine, CA) with intended thickness of 120 microm, and the fellow eye to flap creation with a mechanical microkeratome (Hansatome, Bausch & Lomb, Rochester, NY) with intended thickness of 180 microm. Patients were examined before and at 1, 3, and 6 months after LASIK. MAIN OUTCOME MEASURES: Corneal backscatter, high-contrast visual acuity, manifest refractive error, contrast sensitivity, and intraocular forward light scatter were measured at each examination. Flap thickness was measured by confocal microscopy at 1 month, and patients were asked if they preferred the vision in either eye at 3 months. RESULTS: Corneal backscatter was 6% higher after bladeless LASIK than after LASIK with the mechanical microkeratome at 1 month (P = 0.007), but not at 3 or 6 months. High-contrast visual acuity, contrast sensitivity, and forward light scatter did not differ between treatments at any examination. Flap thicknesses at 1 month were 143+/-16 microm (bladeless, mean +/- standard deviation) and 138+/ 22 microm (mechanical microkeratome), with no statistical difference in variances. At 3 months, 5 patients preferred the bladeless eye, 7 patients preferred the microkeratome eye, and 9 patients had no preference. CONCLUSIONS: The method of flap creation did not affect visual outcomes during the first 6 months after LASIK. Although corneal backscatter was greater early after bladeless LASIK than LASIK with the mechanical microkeratome, patients did not perceive a difference in vision. PMID- 17350689 TI - Pathophysiology of respiratory failure following acute dichlorvos poisoning in a rodent model. AB - Organophosphate (OP) poisoning causes a cholinergic crisis with a wide range of clinical effects including central apnea, pulmonary bronchoconstriction and secretions, seizures, and muscle weakness. The morbidity and mortality from acute OP poisoning is attributed to respiratory failure but the relative contributions of the central and peripheral effects in producing collapse of the respiratory system are unclear. In this study we used a novel adult rat model of acute OP poisoning to analyze the pathophysiology of acute OP poisoning. We found that poisoning caused rapidly lethal central apnea. In animals sustained with mechanical ventilation, we found that following central apnea there ensued progressive pulmonary insufficiency that was variable in timing and severity. Our findings support the hypothesis that OP poisoning in this animal model causes a sequential "two hit" insult, with rapid central apnea followed by delayed impairment of pulmonary gas exchange with prominent airway secretions. PMID- 17350690 TI - Metal ligand substitution and evidence for quinone formation in taurine/alpha ketoglutarate dioxygenase. AB - The three metal-binding ligands of the archetype Fe(II)/alpha-ketoglutarate (alphaKG)-dependent hydroxylase, taurine/alphaKG dioxygenase (TauD), were systematically mutated to examine the effects of various ligand substitutions on enzyme activity and metallocenter properties. His99, coplanar with alphaKG and Fe(II), is unalterable in terms of maintaining an active enzyme. Asp101 can be substituted only by a longer carboxylate, with the D101E variant exhibiting 22% the k(cat) and threefold the K(m) of wild-type enzyme. His255, located opposite the O(2)-binding site, is less critical for activity and can be substituted by Gln or even the negatively charged Glu (81% and 33% active, respectively). Transient kinetic studies of the three highly active mutant proteins reveal putative Fe(IV)-oxo intermediates as reported in wild-type enzyme, but with distinct kinetics. Supplementation of the buffer with formate enhances activity of the D101A variant, consistent with partial chemical rescue of the missing metal ligand. Upon binding Fe(II), anaerobic samples of wild-type TauD and the three highly active variants generate a weak green chromophore resembling a catecholate-Fe(III) species. Evidence is presented that the quinone oxidation state of dihydroxyphenylalanine, formed by aberrant self-hydroxylation of a protein side chain of TauD during aerobic bacterial growth, reacts with Fe(II) to form this species. The spectra associated with Fe(II)-TauD and Co(II)-TauD in the presence of alphaKG and taurine were examined for all variants to gain additional insights into perturbations affecting the metallocenter. These studies present the first systematic mutational analysis of metallocenter ligands in an Fe(II)/alphaKG-dependent hydroxylase. PMID- 17350691 TI - Reliability of the interval death rate analysis for estimating the time course of the motoneurone afterhyperpolarization in humans. AB - The reliability of the afterhyperpolarization (AHP) time course, as estimated by the interval death rate (IDR) analysis was evaluated both within and between investigators. The IDR analysis uses the firing history of a single motor unit train at low tonic firing rates to calculate an estimate of the AHP time course [Matthews PB. Relationship of firing intervals of human motor units to the trajectory of post-spike after-hyperpolarization and synaptic noise. J Physiol 1996;492:597-628]. Single motor unit trains were collected from the tibialis anterior (TA) to determine intra-rater reliability (within investigator). Data from the first dorsal interosseus (FDI), collected in a previous investigation [Gossen ER, Ivanova TD, Garland SJ. The time course of the motoneurone afterhyperpolarization is related to motor unit twitch speed in human skeletal muscle. J Physiol 2003;552:657-64], were used to examine the inter-rater reliability (between investigators). The lead author was blinded to the original time constants and file identities for the re-analysis. The intra-rater reliability of the AHP time constant in the TA data was high (r(2)=0.88; p<0.001; ICC=0.91). The inter-rater reliability for the FDI data was also strong (r(2)=0.92; p<0.001; ICC=0.95). The standard error of measurement was 0.61 ms for the TA and 0.55 ms for FDI. It is concluded that the interval death rate analysis is a reliable tool for estimating the AHP time course with experienced investigators. PMID- 17350692 TI - Lipoteichoic acids selectively stimulate rat mast cells to cysteinyl leukotriene generation and affect mast cell migration after tumor necrosis factor (TNF) priming. AB - It is well established that mast cells play a critical role in the host defense against bacteria. Upon stimulation with bacteria and their antigens, mast cells release various mediators and cytokines that promote the development of inflammation at the site of infection. In the present study, we examined the ability of lipoteichoic acids (LTAs), some of the major components of cell walls of most gram-positive bacteria, to stimulate mast cell degranulation and histamine release as well as to generate of cysteinyl leukotrienes (LTs). We also studied the influence of LTAs on mast cell migration. Experiments were done on rat peritoneal mast cells and LTA from Staphyloccocus aureus and LTA from Bacillus subtilis were used. We have stated that neither S. aureus LTA nor B. subtilis LTA used at a wide range of concentrations (from 10(-4) to 10(5)ng/mL) induced mast cell degranulation and histamine release. However, stimulation of mast cells with both LTAs resulted in generation and release of significant levels of LTs. We have also documented that none of the LTAs stimulated rat mast cell migration, even in the presence of laminin. IL-6 priming did not influence mast cell migration towards LTAs, whereas, pretreatment of mast cells with TNF caused time-dependent mast cell migration in response to LTAs stimulation. Pretreatment of mast cells with anti-TNFR1 antibodies completely inhibited LTA induced migratory response of TNF-primed mast cells. Our results showed that LTAs might be among important bacterial antigens involved in mast cell activation during bacterial infections. PMID- 17350693 TI - New targets for established proteins: exploring G-CSF for the treatment of stroke. AB - Several recent reports describe the efficacy of the hematopoietic factor granulocyte-colony-stimulating factor (G-CSF) in models of stroke and neurodegeneration. Here, we discuss the role of G-CSF as a novel type of multifactorial drug with which to treat stroke, and describe aspects of its modes of action in stroke, in addition to the relationship between clinical trials and the preclinical dataset. Neuroprotective activity in stroke models seems to be based on a direct anti-apoptotic activity in neurons that is mediated by the neuronally expressed G-CSF receptor. Explanations for the long-term effects that improve recovery in different experimental models of stroke include the enhancement of neurogenesis in the adult brain and the stimulation of blood vessel formation. Additional beneficial effects might be based on systemic influences on immunocompetence and inflammation parameters, and the activation of bone-marrow-derived stem cells. Several clinical trials have been initiated in stroke patients, mainly to demonstrate the safety of G-CSF in this setting. PMID- 17350694 TI - The endocannabinoid system in targeting inflammatory neurodegenerative diseases. AB - The classical divide between degenerative and inflammatory disorders of the CNS is vanishing as accumulating evidence shows that inflammatory processes are important in the pathophysiology of primarily degenerative disorders, and neurodegeneration complicates primarily inflammatory diseases of the brain and spinal cord. Here, we review the contribution of degenerative and inflammatory processes to CNS disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis and HIV-associated dementia. An early combination of neuroprotective and anti-inflammatory approaches to these disorders seems particularly desirable because isolated treatment of one pathological process might worsen another. We also discuss the apparently unique opportunity to modify neurodegeneration and neuroinflammation simultaneously by pharmacological manipulation of the endocannabinoid system in the CNS and in peripheral immune cells. Current knowledge of this system and its involvement in the above CNS disorders are also reviewed. PMID- 17350695 TI - Effects of sublethal abiotic stressors on population growth and genetic diversity of Pellioditis marina (Nematoda) from the Westerschelde estuary. AB - Understanding the effects of anthropogenic pollutants at the ecosystem level requires a proper understanding of the toxicological effects at the population level. Species living in estuaries resist highly fluctuating conditions, and are often exposed to sublethal concentrations of pollutants coming from industrial and domestic wastes. In the Westerschelde estuary, the most upstream sampled population of the nematode Pellioditis marina is genetically less diverse than elsewhere. It experiences lower salinities and higher Cd concentrations than more downstream populations in the estuary. In the present study, we investigate whether these environmental conditions may explain the lower genetic diversity in the most upstream location. To this end we followed the development of genetically diverse P. marina populations under experimental conditions during 14 days. Genetic diversity was assessed in the F1, F2 and F5 generation by screening mitochondrial cytochrome oxidase c subunit 1 variation with the single-strand conformation polymorphism method (SSCP) and nucleotide sequencing. Our results show that sublethal Cd concentrations reduce population development of P. marina at suboptimal salinities, and that low salinity conditions induce responses at the genetic level. Nevertheless, the genetic effects were not persistent over generations, which emphasize the need for longer multigenerational experiments. PMID- 17350696 TI - Evidence for changes in the transcription levels of two putative P-glycoprotein genes in sea lice (Lepeophtheirus salmonis) in response to emamectin benzoate exposure. AB - Overexpression of P-glycoproteins (Pgps) is assumed to be a principal mechanism of resistance of nematodes and arthropods to macrocyclic lactones. Quantitative RT-PCR (Q-RT-PCR) was used to demonstrate changes in transcription levels of two putative P-glycoprotein genes, designated here as SL0525 and SL-Pgp1, in sea lice (Lepeophtheirus salmonis) following exposure to emamectin benzoate (EMB). Pre adult L. salmonis were challenged in an EMB bioassay for 24h and gene expression was studied from lice surviving EMB concentrations of 0, 10, and 30ppb. Gene expression was measured using Q-RT-PCR with elongation factor 1 (eEF1alpha) as an internal reference gene. The results show that both target genes, SL0525 and SL Pgp1, had significantly increased levels of expression with exposure to 10ppb EMB (p=0.11 and p=0.17, respectively) whereas the group exposed to 30ppb was on the verge of being significant (p=0.053) only in the expression of SL-Pgp1. Gene expression for SL0525 and SL-Pgp1 were increased over five-fold at 10ppb EMB. Therefore, the upregulation of these target genes may offer protection by increasing Pgp expression when lice are exposed to EMB. Our optimized Q-RT-PCR can be used to determine if over-expression of these genes could be the basis for development of resistance in sea lice and thus allow suitable alternative chemotherapeutic options to be assessed. PMID- 17350697 TI - Challenged sodium balance and expression of angiotensin type 1A receptor mRNA in the hypothalamus of Wistar and Dahl rat strains. AB - The present study investigates the influence of a chronic high Na+ diet (8% Na+) on the expression of the angiotensin type 1A (AT1A) receptor gene in the lamina terminalis and paraventricular nucleus of the hypothalamus (PVH) in normotensive Wistar (W) rats, as well as in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats. Three weeks of 8% Na+ diet led to a higher blood pressure in DS rats compared to DR and W rats. Moreover, the high Na+ diet was correlated with a decreased expression of AT1A receptor mRNA in the median preoptic nucleus (MnPO) and in the PVH of DS rats, compared to DR and W rats. Contrastingly, the AT1A receptor mRNA expression was not altered by the high Na+ diet in the forebrain circumventricular organs of all the rat strains. Interestingly, a furosemide induced Na+ depletion was correlated with an increased expression of AT1A receptor mRNA in the PVH, MnPO and SFO of both the DS and DR rats. It is concluded that chronic high Na+ diet did differently regulate the expression of AT1A receptor mRNA in two hypothalamic integrative centers for hydromineral and cardiovascular balance (the PVH and MnPO) in DS rats, compared to DR and W rats. However, the AT1A receptor mRNA expression was similarly regulated in DS and DR rats in response to an acute Na+ depletion, suggesting a distinct high Na+ induced regulation of the AT1A receptor gene in the PVH and MnPO of DS rats. PMID- 17350698 TI - The effect of co-morbidity on the rehabilitation process in elderly patients after hip fracture. AB - We conducted a prospective observational study involving patients older than 65 years admitted for rehabilitation to the Geriatric Department of a university hospital after surgical treatment of hip fracture. We assessed functional status before, during and at the end of rehabilitation and as a measure of success of rehabilitation we calculated the Montebello Rating Factor Score (MRFS). In an attempt to make this index more reflective of changes in rehabilitative status we revised it accordingly. We measured demographic characteristics, cognitive function, affective status and co-morbidity. Data were collected from 102 patients with average age 79.0+/-6.5 years over a period of 12 months. In the uinvariant analysis, cognitive status, length of stay in Geriatric Department and co-morbidity were found as significant predictors of rehabilitation success. In the linear regression only Severity Index (SI) of Cumulative Illness Rating Scale for Geriatrics (CIRS-G) was found as a statistically significant predictor of rehabilitation outcome. In our context, we found that only co-morbidity (as measured by CIRS) is the best predictor of rehabilitation outcome of elderly patients after surgical repair of hip fracture. PMID- 17350699 TI - Influence of level of activity on cognitive performance and cognitive plasticity in elderly persons. AB - As a result of the rapid increase in the elderly population over recent decades, the analysis of factors influencing cognitive aging has become a focus of great interest for current research. In this area, numerous papers have indicated a relation between specific psychosocial variables and the level of activity and cognitive performance and plasticity in old age. This study aimed at testing a theoretical model, which establishes relations between level of activity, cognitive performance and cognitive plasticity in old age. In this study 176 elderly persons participated and were evaluated by means of a cognitive screening test, two cognitive plasticity evaluation tests and a questionnaire on the level of activity before and after retirement. A structural equation analysis was carried out on the data, which reveal significant relations between level of activity after retirement and cognitive performance and plasticity. Similarly, a significant relation is established between cognitive functioning and plasticity. The findings lend support to studies affirming that a high level of activity protects against cognitive decline and is related to cognitive plasticity in old age. PMID- 17350700 TI - Coronary risk factors and coronary atheroma burden at severely narrowing segments. AB - BACKGROUND: While only few data exist correlating cardiovascular risk factors with volumetric measurements of coronary atheroma burden in patients with coronary artery disease, a recent report using intravascular ultrasound (IVUS) demonstrated independent predictors of atherosclerotic burden in a native coronary artery with relatively mild narrowing (20-50% diameter stenosis by visual estimation). The purpose of this study was to examine whether cardiovascular risk factors can predict atherosclerotic burden at severely narrowing segments (>50% diameter stenosis). METHODS: Patients who met the criteria (high-quality, automated pull-back IVUS images of severely narrowing segments prior to intervention) were identified from the IVUS database of the Cardiovascular Core Analysis Laboratory at Stanford University. Using commercially available planimetry software, lumen and vessel inside external elastic membrane areas were manually traced at every 0.5-mm interval in diseased segments. Using Simpson's method, vessel, lumen, and plaque (vessel minus lumen) volumes were calculated, and average area was calculated as volume data divided by length. Percent plaque volume was computed as plaque volume divided by vessel volume. Multiple linear regression analysis with backward selection was used to determine the risk factors for atherosclerotic burden. RESULTS: For percent plaque volume, diabetes or hypertension were predictors of more severe disease. For average plaque area, male gender or diabetes were predictors of more severe disease. These variables were also independent predictors in multivariate regression models. CONCLUSIONS: Male gender, hypertension, and diabetes are also strong independent predictors of atherosclerotic burden in coronary disease patients, though analyzed segments and disease severity were different. PMID- 17350701 TI - Coronary narrowing secondary to compression by pericardial hydatid cyst. AB - Echinococcus granulosus remains a clinical problem in undeveloped and developing countries. It commonly affects the liver and lung, but, rarely, other organs such as the heart can be involved. In this report, we describe an unusual case in which pericardial hydatid cyst mimicking acute coronary syndrome secondary to compression by pericardial hydatid cyst attached to the anterolateral wall of the left ventricle. We made diagnosis by transthoracic 2D echocardiography, and confirmed by cardiac magnetic resonance imaging and serologic tests. Because our patient refused to have an operation, albendazole therapy was given. It is important to recognize this unusual disease, because it may lead to serious complications. PMID- 17350702 TI - Respiratory waveform facilitating recognition of hiccup-induced electrocardiographic artifacts. PMID- 17350703 TI - Effect of Mycobacterium paratuberculosis infection on production, reproduction, and health traits in US Holsteins. AB - Our objective was to estimate the effect of Mycobacterium paratuberculosis infection on milk, fat, and protein yield deviations, pregnancy rate, lactation somatic cell score, and projected total months in milk (productive life). A serum ELISA and fecal culture for M. paratuberculosis were performed on 4375 Holsteins in 232 DHIA herds throughout the US. Primarily first through third lactation cows (99% of total) were assayed for infection. Trait information (except productive life) was obtained for the lactation concurrent with disease tests. Productive life was total months in milk through a cow's life, which was projected if a cow was still milking. For most analyses, case definition for M. paratuberculosis infection was defined as either an ELISA S/P ratio>or=0.25 or a positive fecal culture for M. paratuberculosis or both. To determine if diagnostic test affected estimates, case definition was redefined to include only cows with ELISA S/P ratios>or=0.25 or only fecal culture-positive cows. Linear models were used to estimate effect of M. paratuberculosis infection on traits. M. paratuberculosis infected cows (7.89% of cows) produced 303.9 kg less milk/lactation, 11.46 kg less fat/lactation, and 9.49 kg less protein/lactation (P or =15% were 6.6 (5.4, 8.2), 5.5 (4.7, 6.5), 5.6 (4.8, 6.6), and 3.5 (3.0, 4.1), for the WHO, ATPIII, IDF, and EGIR definitions, respectively. The population attributable risk (PAR) of high CVD risk due to the MetS was highest for the IDF (23.4%). Insulin resistance was detected in 56.1, 69.7, 50.9, and 91.1% of those meeting the ATPIII, WHO, IDF, and EGIR definitions, respectively. CONCLUSION: The WHO definition was associated with the greatest CVD risk, but is not practical for clinical use. The higher PAR due to the IDF definition, with only slightly lower CVD risk than WHO, and clinical utility of the IDF definition, indicates that it may be a useful tool for CVD prevention. PMID- 17350711 TI - Simulation of cardiovascular system diseases by including the autonomic nervous system into a minimal model. AB - Diagnosing cardiovascular system (CVS) diseases from clinically measured data is difficult, due to the complexity of the hemodynamic and autonomic nervous system (ANS) interactions. Physiological models could describe these interactions to enable simulation of a variety of diseases, and could be combined with parameter estimation algorithms to help clinicians diagnose CVS dysfunctions. This paper presents modifications to an existing CVS model to include a minimal physiological model of ANS activation. A minimal model is used so as to minimise the number of parameters required to specify ANS activation, enabling the effects of each parameter on hemodynamics to be easily understood. The combined CVS and ANS model is verified by simulating a variety of CVS diseases, and comparing simulation results with common physiological understanding of ANS function and the characteristic hemodynamics seen in these diseases. The model of ANS activation is required to simulate hemodynamic effects such as increased cardiac output in septic shock, elevated pulmonary artery pressure in left ventricular infarction, and elevated filling pressures in pericardial tamponade. This is the first known example of a minimal CVS model that includes a generic model of ANS activation and is shown to simulate diseases from throughout the CVS. PMID- 17350712 TI - Peripheral arterial ischemia by a primary lung tumour invading left atrium. AB - Peripheral arterial embolism from a malignant tumour is an uncommon manifestation of a neoplasm. Here, we present a case of acute upper limb ischemia due to an embolus originating from primary lung malignancy invading the left atrium. PMID- 17350713 TI - CD63 as a biomarker for predicting the clinical outcomes in adenocarcinoma of lung. AB - BACKGROUND: The prognosis of lung cancer is still poor, since there are few early detection tools available yet. So, it is important to identify more efficient and clinically applicable biomarkers associated with the prognosis in as earlier stages as possible. PATIENTS AND METHODS: In this study, we observed the expression of CD63 in 90 cases of non-small cell lung cancer (NSCLC) to explore the potential of this molecule as a prognostic biomarker for lung cancer subtypes using real-time quantitative RT-PCR and tissue microarray based immunohistochemistry. RESULTS: Majority of NSCLCs (75.8%) showed lower CD63 RNA level (less than half) than normal tissue. Notably, all SqCs showed low expression except one case, while AdCs showed diverse range of expression. CD63 protein expression level was largely compatible with RNA level. Totally, 63.3% of NSCLC were CD63 protein expression negative. All SqCs were negative, while majority (70.2%) of adenocarcinomas (AdCs) were positive. CD63 protein negativity was significantly associated with SqCs type, larger tumor size, and advanced stage. In AdCs, CD63 negativity was associated with poor survival (p=0.008). This association was also significant in earlier stage (I and II) AdCs (p=0.041), but not in advanced stage AdCs. After being adjusted for age and sex by Cox regression and stratified by stages, CD63 negativity still showed borderline association with poor survival as an independent predictor (p=0.076, HR=2.3). CONCLUSIONS: Taken together, these results suggest that CD63 can be a biomarker for predicting the prognosis in earlier stage of lung AdCs. Our findings can be a clue to investigate the role of CD63 in tumorigenesis of AdCs of lung and other cancers. PMID- 17350714 TI - The ups and downs of trophic control in continental shelf ecosystems. AB - Traditionally, marine ecosystem structure was thought to be determined by phytoplankton dynamics. However, an integrated view on the relative roles of top down (consumer-driven) and bottom-up (resource-driven) forcing in large-scale, exploited marine ecosystems is emerging. Long time series of scientific survey data, underpinning the management of commercially exploited species such as cod, are being used to diagnose mechanisms that could affect the composition and relative abundance of species in marine food webs. By assembling published data from studies in exploited North Atlantic ecosystems, we found pronounced geographical variation in top-down and bottom-up trophic forcing. The data suggest that ecosystem susceptibility to top-down control and their resiliency to exploitation are related to species richness and oceanic temperature conditions. Such knowledge could be used to produce ecosystem guidelines to regulate and manage fisheries in a sustainable fashion. PMID- 17350715 TI - The Pleistocene re-wilding gambit. AB - Re-wilding parts of North America with exotic Old-World species is an exciting but controversial conservation proposal hijacked by opinions over appropriate conservation baselines and details of implementation. Debate over its worth has become partisan. Here, I summarize the multifaceted issues surrounding Pleistocene re-wilding and edge debate from hazy conceptual arguments to empirical questions that can plug gaps in knowledge and begin to resolve this divisive conservation issue. PMID- 17350716 TI - Three-dimensional visualization and quantification of non-aqueous phase liquid volumes in natural porous media using a medical X-ray Computed Tomography scanner. AB - This study demonstrates the capabilities of a typical medical X-ray Computed Tomography (CT) scanner to non-destructively quantify non-aqueous phase liquid (NAPL) volumes, saturation levels, and three-dimensional spatial distributions in packed soil columns. Columns packed with homogeneous sand, heterogeneous sand, or natural soil, were saturated with water and injected with known quantities of gasoline or tetrachloroethene and scanned. A methodology based on image subtraction was implemented for computing soil porosity and NAPL volumes in each 0.35 mm x 0.35 mm x 1 mm voxel of the columns. Elimination of sample positioning errors and instrument drift artifacts was essential for obtaining reliable estimates of above parameters. The CT data-derived total NAPL volume was in agreement with the measured NAPL volumes injected into the columns. CT data derived NAPL volume is subject to a 2.6% error for PCE and a 15.5% error for gasoline, at average NAPL saturations as low as 5%, and is mainly due to instrument noise. Non-uniform distributions of NAPL due to preferential flow, and accumulation of NAPL above finer-grained layers could be observed from the data on 3-D distributions of NAPL volume fractions. PMID- 17350717 TI - Pulsed pumping process optimization using a potential flow model. AB - A computational model is applied to the optimization of pulsed pumping systems for efficient in situ remediation of groundwater contaminants. In the pulsed pumping mode of operation, periodic rather than continuous pumping is used. During the pump-off or trapping phase, natural gradient flow transports contaminated groundwater into a treatment zone surrounding a line of injection and extraction wells that transect the contaminant plume. Prior to breakthrough of the contaminated water from the treatment zone, the wells are activated and the pump-on or treatment phase ensues, wherein extracted water is augmented to stimulate pollutant degradation and recirculated for a sufficient period of time to achieve mandated levels of contaminant removal. An important design consideration in pulsed pumping groundwater remediation systems is the pumping schedule adopted to best minimize operational costs for the well grid while still satisfying treatment requirements. Using an analytic two-dimensional potential flow model, optimal pumping frequencies and pumping event durations have been investigated for a set of model aquifer-well systems with different well spacings and well-line lengths, and varying aquifer physical properties. The results for homogeneous systems with greater than five wells and moderate to high pumping rates are reduced to a single, dimensionless correlation. Results for heterogeneous systems are presented graphically in terms of dimensionless parameters to serve as an efficient tool for initial design and selection of the pumping regimen best suited for pulsed pumping operation for a particular well configuration and extraction rate. In the absence of significant retardation or degradation during the pump-off phase, average pumping rates for pulsed operation were found to be greater than the continuous pumping rate required to prevent contaminant breakthrough. PMID- 17350719 TI - A voluntary ingestion of alcohol-based hand rub. PMID- 17350718 TI - Matrix diffusion coefficients in volcanic rocks at the Nevada test site: influence of matrix porosity, matrix permeability, and fracture coating minerals. AB - Diffusion cell experiments were conducted to measure nonsorbing solute matrix diffusion coefficients in forty-seven different volcanic rock matrix samples from eight different locations (with multiple depth intervals represented at several locations) at the Nevada Test Site. The solutes used in the experiments included bromide, iodide, pentafluorobenzoate (PFBA), and tritiated water ((3)HHO). The porosity and saturated permeability of most of the diffusion cell samples were measured to evaluate the correlation of these two variables with tracer matrix diffusion coefficients divided by the free-water diffusion coefficient (D(m)/D*). To investigate the influence of fracture coating minerals on matrix diffusion, ten of the diffusion cells represented paired samples from the same depth interval in which one sample contained a fracture surface with mineral coatings and the other sample consisted of only pure matrix. The log of (D(m)/D*) was found to be positively correlated with both the matrix porosity and the log of matrix permeability. A multiple linear regression analysis indicated that both parameters contributed significantly to the regression at the 95% confidence level. However, the log of the matrix diffusion coefficient was more highly correlated with the log of matrix permeability than with matrix porosity, which suggests that matrix diffusion coefficients, like matrix permeabilities, have a greater dependence on the interconnectedness of matrix porosity than on the matrix porosity itself. The regression equation for the volcanic rocks was found to provide satisfactory predictions of log(D(m)/D*) for other types of rocks with similar ranges of matrix porosity and permeability as the volcanic rocks, but it did a poorer job predicting log(D(m)/D*) for rocks with lower porosities and/or permeabilities. The presence of mineral coatings on fracture walls did not appear to have a significant effect on matrix diffusion in the ten paired diffusion cell experiments. PMID- 17350720 TI - Surveillance of extended-spectrum beta-lactamase-producing bacteria and routine use of contact isolation: experience from a three-year period. AB - The usefulness and applicability of isolation precautions were questioned for extended-spectrum beta-lactamase (ESBL)-producing strains of Enterobacteriaceae in the endemic setting. We performed a surveillance programme for ESBL-positive organisms and the infection control management of patients colonized or infected with these organisms. Between 1 January 2002 and 31 December 2004, a total of 147 cases of ESBL-producing strains of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis from 123 patients were noted. The overall incidence of ESBL producing-strain-positive cases was 0.12/1000 patient-days. The proportion of referred cases was 35% (N=51); 65% of cases (N=96) were acquired in our institution. Infections developed in 57 cases (38.8%), of which 36 (63.3%) were nosocomial. Contact isolation precautions were carried out for 79.6% of the cases, with a median duration of contact isolation precautions for 14 days (range: 0-144). The contact isolation precautions resulted in 2985 isolation days in total, i.e. 995 isolation days per year. Typing by pulsed-field gel electrophoresis showed clonal diversity in 94.2% of the isolates from patients. Seven patient-to-patient transmissions were noted. Only in 10 cases (6.8%) was colonization with ESBL-producing strains cleared. Considering the large number of immunocompromised patients treated in our institution (>1500 bone marrow or solid organ transplantations performed during 2002-2004), we will continue to isolate patients who are colonized or infected with ESBL-producing organisms. PMID- 17350721 TI - Inadequate treatment of ventilator-associated pneumonia: risk factors and impact on outcomes. AB - Initial antibiotic therapy is an important determinant of clinical outcomes in ventilator-associated pneumonia (VAP). Several studies have investigated this issue, with conflicting results. This study investigated risk factors of inadequate empirical antimicrobial therapy and its impact on outcomes for patients with a clinical diagnosis of VAP. The primary outcome was adequacy of antimicrobial therapy. Secondary outcomes were duration of mechanical ventilation, hospital and intensive care unit (ICU) lengths of stay, and mortality due to VAP. Mean age was 62.9+/-15.2 years, mean APACHE (Acute Physiological Assessment and Chronic Health Evaluation) II score was 20.1+/-8.1 and mean MODS (Multiple Organ Dysfunction Score) was 3.7+/-2.5. Sixty-nine (45.7%) of 151 patients with a clinical diagnosis of VAP received inadequate antimicrobial treatment for VAP initially. There were 100 (66.2%) episodes of VAP caused by multidrug-resistant pathogens, of which 56% were inadequately treated, whereas the rate of inadequate antimicrobial therapy for VAP caused by susceptible-drug pathogens was 25.5% (P<0.001). Multiple logistic regression analysis revealed that the risk of inadequate antimicrobial treatment was more than twice as great for patients with late-onset VAP [odds ratio (OR), 2.93; 95% confidence interval (CI), 1.30-6.64; P=0.01], and more than three times for patients with VAP caused by multidrug-resistant pathogens (OR, 3.07; 95% CI, 1.29 7.30; P=0.01) or with polymicrobial VAP (OR, 3.67; 95% CI, 1.21-11.12; P=0.02). Inadequate antimicrobial treatment was associated with higher mortality for patients with VAP. Two of three independent risk factors for treatment inadequacy were associated with the isolation and identification of micro-organisms. PMID- 17350722 TI - Effect of neonatal intensive care unit environment on the incidence of hospital acquired infection in neonates. AB - The influence of the inanimate hospital environment and hospital design on nosocomial infection is a topic for discussion. This study evaluated the impact of the neonatal intensive care unit (NICU) environment on the risk of hospital acquired infection (HAI). HAI surveillance was performed during a four-year period when the NICU was moved initially from an old facility to temporary accommodation and then eventually to a new and better-designed facility. The rate of HAI rose significantly from 12.8 to 18.6% (P<0.01) after moving to the temporary unit, which had a lower sink:cot ratio and a higher monthly admission rate. In contrast, the rates of catheter-associated staphylococcal bacteraemia decreased significantly after moving to the new NICU (P<0.0001). Since peripherally inserted central catheters (PICCs) were introduced concomitantly with the move to the new unit, however, the catheter type may have contributed towards this reduction in CVC-related staphylococcal bacteraemias. Moving to a temporary NICU with poor handwashing facilities and higher admission activity resulted in higher rates of HAI. PMID- 17350723 TI - Acceptance of influenza vaccination by nursing personnel in Mexico. PMID- 17350724 TI - Control and prevention of healthcare-associated tuberculosis: the role of respiratory isolation and personal respiratory protection. AB - Although the prevalence of tuberculosis continues to decline in most developed countries, the risk of healthcare-associated tuberculosis, remains for patients or healthcare staff. Outbreaks of healthcare-associated tuberculosis are usually associated with delays in diagnosis and treatment, or the care of patients in sub optimal facilities. The control and prevention of tuberculosis in hospitals is best achieved by three approaches, namely administrative (early investigation diagnosis, etc.), engineering (physical facilities e.g. ventilated isolation rooms) and personal respiratory protection (face sealing masks which are filtered). Recent guidelines on the prevention of tuberculosis in healthcare facilities from Europe and the USA have many common themes. In the UK, however, negative pressure isolation rooms are recommended only for patients with suspected multi-drug resistant TB and personal respiratory protection, i.e. filtered masks, are not considered necessary unless multi-drug resistant TB is suspected, or where aerosol-generating procedures are likely. In the US, the standard of care for patients with infectious tuberculosis is a negative pressure ventilated room and the use of personal respiratory protection for all healthcare workers entering the room of a patient with suspected or confirmed tuberculosis. The absence of clinical trials in this area precludes dogmatic recommendations. Nonetheless, observational studies and mathematical modelling suggest that all measures are required for effective prevention. Even when policies and facilities are optimal, there is a need to regularly review and audit these as sometimes compliance is less than optimal. The differences in recommendations may reflect the variations in epidemiology and the greater use of BCG vaccination in the UK compared with the United States. There is a strong argument for advising ventilated facilities and personal respiratory protection for the care of all patients with tuberculosis, as multi-drug tuberculosis may not always be apparent on admission, and these measures minimise transmission of all cases of TB to other patients and healthcare staff. PMID- 17350725 TI - Doctors' awareness of their patients' urinary catheterization status. PMID- 17350726 TI - Healthcare-associated infections in neonatal units: lessons from contrasting worlds. AB - Neonatal intensive care units are vulnerable to outbreaks and sporadic incidents of healthcare-associated infections (HAIs). The incidence and outcome of these infections are determined by the degree of immaturity of the neonatal immune system, invasive procedures involved, the aetiological agent and its antimicrobial susceptibility pattern and, above all, infection control policies practised by the unit. It is important to raise awareness of infection control practices in resource-limited settings, since overdependence upon antimicrobial agents and co-existing lack of awareness of infection control is encouraging the emergence of multi-drug-resistant nosocomial pathogens. We reviewed 125 articles regarding HAIs from both advanced and resource-limited neonatal units in order to study risk factors, aetiological agents, antimicrobial susceptibility patterns and reported successes in infection control interventions. The articles include surveillance studies, outbreaks and sporadic incidents. Gram-positive cocci, viruses and fungi predominate in reports from the advanced units, while Gram negative enteric rods, non-fermenters and fungi are commonly reported from resource-limited settings. Antimicrobial susceptibility patterns from surveillance studies determined the empirical therapy used in each neonatal unit. Most outbreaks, irrespective of the technical facilities available, were traced to specific lack of infection control practices. We discuss infection control interventions, with special emphasis on their applicability in resource-limited settings. Cost-effective measures for implementing these interventions, with particular reference to the recognition of the role of the microbiologist, the infection control team and antibiotic policies are presented. PMID- 17350727 TI - Environmental contamination following toilet use in the operating department. PMID- 17350728 TI - Distribution of the antiseptic-resistance genes qacEDelta1 in 331 clinical isolates of Pseudomonas aeruginosa in China. PMID- 17350729 TI - Inactivation of Norovirus by ozone gas in conditions relevant to healthcare. AB - We evaluated the ability of ozone gas to inactivate Norovirus and its animal surrogate feline calicivirus (FCV) in dried samples placed at various locations within a hotel room, a cruise liner cabin and an office. Norovirus was measured by quantitative reverse transcriptase real-time polymerase chain reaction (QRT PCR) assay, and FCV by a combination of QRT-PCR and virus infectivity assays. We were able to reduce the concentration of infectious FCV by a factor of more than 10(3), and in some cases beyond detection, under optimal conditions of ozone exposure with less than an hour of total operation. QRT-PCR assays indicated similar decreases in both viral RNAs. Virus-containing samples dried onto hard surfaces (plastic, steel and glass), and soft surfaces such as fabric, cotton and carpet, were equally vulnerable to the treatment. Our results show that Norovirus can be inactivated by exposure to ozone gas from a portable commercial generator in settings such as hotel rooms, cruise ship cabins and healthcare facilities. PMID- 17350730 TI - Reducing neonatal nosocomial bloodstream infections through participation in a national surveillance system. AB - A national nosocomial surveillance system for neonatal intensive care patients with a very low birthweight was set up in Germany in 2000 (NEO-KISS). Forty-eight neonatal intensive care units (NICUs) participated in the programme, which focused upon nosocomial bloodstream infections (BSIs) and pneumonia. Only data from NICUs participating for at least three years were included and the years compared. The relative risks and their 95% confidence intervals (CIs) were calculated and a multiple logistic regression analysis performed to identify significant risk factors. Twenty-four units that met the selection criteria accumulated data for 3856 patients and 152 437 patient-days in their first three years of participation. The incidence density of BSIs decreased significantly by 24% from 8.3 BSIs per 1000 patient-days in the first year to 6.4 in the third year. In the multiple logistic regression analysis, BSI in the third year of participation was significantly lower than in the first year of participation (odds ratio=0.73, 95% CI 0.60-0.89). The year of participation was an independent risk factor for BSI but not for pneumonia. Our data suggest that participation in ongoing surveillance of nosocomial infections in NICUs, requiring individual units to feedback data, may lead to a reduction in BSI rates. PMID- 17350731 TI - Closure of medical departments during nosocomial outbreaks: data from a systematic analysis of the literature. AB - A total closure of an affected medical department is one of the most expensive infection control measures during investigation of a nosocomial outbreak. However, until now there has been no systematic analysis of typical characteristics of outbreaks, for which closure was considered necessary. This article presents data on features of such nosocomial epidemics published during the past 40 years in the medical literature. A search of the Outbreak Database (1561 nosocomial outbreaks in file) revealed a total of 194 outbreaks that ended up with some kind of closure of the unit (median closure time: 14 days). Closure rates (CRs) were calculated and stratified for medical departments, for causative pathogens, for outbreak sources, and for the assumed mode of transmission. Data were then compared to the overall average CR of 12.4% in the entire database. Wards in geriatric patient care were closed significantly more frequently (CR: 30.3%; P<0.001) whereas paediatric wards showed a significantly lower CR (6.1%; P=0.03). Pathogen species with the highest CR were norovirus (44.1%; P<0.001) and influenza/parainfluenza virus (38.5%; P<0.001). If patients were the source of the outbreak, the CR was significantly increased (16.7%; P=0.03). Infections of the central nervous system were most often associated with closure of the ward (24.2%; P=001). A systematic evaluation of nosocomial outbreaks can be a valuable tool for education of staff in the absence of an outbreak, but may be even more helpful for potentially cost-intensive decisions in the acute outbreak setting on the ward. PMID- 17350732 TI - Measuring antibiotic timing for pneumonia in the emergency department: another nail in the coffin. PMID- 17350733 TI - Impairment of spatial memory consolidation in APP(751SL) mice results in cue guided response. AB - APP(751SL) mice of 5-6- and 7-8-month-old and their wild-type littermates were submitted to one-session learning in a water-maze with three levels of training (4, 12 or 22 trials). Training consisted in finding a submerged platform with a fixed location and marked by a cue. During testing two platforms were presented: one consistent with the spatial location allowing place-response (PR) and the other signaled by the cue enabling cued-response (CR). When testing occurred 24h after training, wild-type and 5-6-month-old APP(751SL) mice exhibited a shift in response strategy as a function of training level, by executing CR when trained with 4 trials and PR when trained with 12 trials, but 7-8-month-old APP(751SL) mice executed only CR. However, they displayed PR when tested 1h after 12- and 22 trial, suggesting a consolidation deficit. Zif268 imaging showed plasticity impairment of the hippocampal-dependent memory system but not of the dorsolateral caudate nucleus. Moreover, in these APP(751SL) mice, the deficit selectively affecting hippocampal function cannot be directly related to the onset of beta amyloid deposits. PMID- 17350734 TI - Raman, FT-IR, NMR spectroscopic data and antimicrobial activity of bis[micro2 (benzimidazol-2-yl)-2-ethanethiolato-N,S,S-chloro-palladium(II)] dimer, [(micro2 CH2CH2NHNCC6H4)PdCl]2.C2H5OH complex. AB - The 1,6-bis(benzimidazol-2-yl)-3,4-dithiahexane (1) ligand and its palladium(II) chloride complex [(micro(2)-SCH(2)CH(2)NHNCC(6)H(4))PdCl](2)xC(2)H(5)OH (2) have been synthesised and characterised by spectroscopical methods. The crystal structure of the triclinic title compound (P-1 (no. 2), a=879.6(1) pm, b=984.4(1) pm, c=1471.8(2) pm; alpha=94.330(6) degrees , beta=98.546(6) degrees , gamma=99.258(7) degrees , Z=2) was solved from X-ray single crystal diffraction data. In the binuclear complex, each palladium atom is coordinated in a slightly distorted square-planar arrangement by one nitrogen, two bridging sulphurs and one terminal chlorine atom. Molar conductivity, FT-Raman, FT-IR (mid-i.r., far i.r.), (1)H and (13)C NMR spectra of the complex (2) have been recorded and show a good accordance with the square-planar geometry. The antimicrobial and antifungal activities of palladium(II) chloride, free ligand, its hydrochloride salt and the complex were evaluated using the disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) the dilution method, against 10 bacteria and five yeast cultures. The results for the antibacterial from the disk diffusion method were assessed in side-by-side comparison with those for penicillin-g, ampicillin, cefotaxime, vancomycin, ofloxacin and tetracycline. Antifungal activities were referenced with nystatin, ketaconazole, and clotrimazole, commercial antifungal agents. The data from the dilution procedure were compared with gentamycin as antibacterial and nystatin as antifungal agent, respectively. In most cases, the compounds tested showed broad spectrum (Gram positive and Gram negative) activities that were comparatively more active, or as potent as referenced pharmaceutical agents. The palladium complex has the potential to generate new kind of metabolites by displaying high affinities for most of the receptors compared with palladium chloride, free ligand and its hydrochloride salt. PMID- 17350735 TI - Chemical adjuvants for plasmid DNA vaccines. AB - Plasmid DNA vaccines are a promising modality for immunization against a variety of human pathogens. Immunization via multiple routes with plasmid DNA can elicit potent cellular immune responses, and these immunogens can be administered repeatedly without inducing anti-vector immunity. Nonetheless, the immunogenicity of plasmid DNA vaccines has been limited by problems associated with delivery. A number of adjuvants have been designed to improve plasmid DNA immunogenicity, either by directly stimulating the immune system or by enhancing plasmid DNA expression. Chemical adjuvants for enhancing plasmid DNA expression include liposomes, polymers, and microparticles, all of which have shown promise for enhancing the expression and immunogenicity of plasmid DNA vaccines in animal models. Micro- and nanoparticles have not been shown to enhance immune responses to plasmid DNA vaccines. However, formulation of plasmid DNA with some non particulate polymeric adjuvants has led to a statistically significant enhancement of immune responses. Further development of these technologies will significantly improve the utility of plasmid DNA vaccination. PMID- 17350737 TI - Open rhinoplasty for African-American noses. AB - Our aim was to evaluate the use of open rhinoplasty for cosmesis on African American noses. Thirty African-American patients with Fitzpatrick skin type V or VI and typical African-American noses who had had open rhinoplasty between January 1997 and November 2000, and at least 3-years' follow-up were selected and their casenotes examined retrospectively. Patients' evaluations were recorded at all consultations and the data was recorded on standard protocols together with objective measurements including wound healing and complications. All patients thought that the definition and projection of the tip was successful and 27 of the under projected tips were improved. Two had a persistently slightly wider interalar distance than they wanted. In one the nostrils were asymmetrical. The nasal dorsum was improved in all patients, with no complaints of under or over correction. Revision was necessary in one patient who complained of mobility of the silicone rubber (Silastic) implant that had been placed over the anterior nasal spine. Only one patient was unsatisfied on the subjective evaluation. Columellar scarring was noticed only by the staff, and there were no signs of keloid and hypopigmentation, or hyperpigmentation. Postoperatively, there were two synechiae and one haemorrhage. Open rhinoplasty using the transcolumellar external incision for aesthetic correction of African-American noses gives satisfactory results with few complications. PMID- 17350736 TI - Comparison of immunogenicity between codon optimized HIV-1 Thailand subtype B gp140 and gp145 vaccines. AB - HIV-1 pandemic posed an unprecedented challenge to the global health and it is believed that an effective vaccine will be the final solution against HIV-1. HIV 1 envelope is the primary immunogen in developing neutralization antibody based HIV vaccine. To define the suitable Env derived immunogen, we systemically compared the immunogenicity of gp140 and gp145 in a DNA vaccination alone and a prime-boost modalities. Two DNA vaccines and two recombinant Tiantan vaccinia vaccines (rTTV) were constructed for vaccination of female Balb/c mice. Elispot assay was used to read out the T cell immunity and ELISA assay was used to quantify antibody immunity. PLL (poly-L-leucine)-ELISA assay was used in linear antibody epitope mapping. Mice primed with gp145 tended to elicit more Env specific T cells responses than those primed with gp140, significant difference was observed in DNA immunization alone. The ultimate T cell responses in prime boost regimen tend to be determined mainly by the priming efficacy. Linear antibody epitope mapping displayed that sera raised by gp145 priming were vigorously reactive to more peptides than that by gp140. Our data demonstrated HIV-1 Thailand B-derived gp145 may raise higher T-cell responses and broader linear peptide-specific antibody responses than gp140 does. However, it remains to be determined that how these observations are relevant to the neutralization of antibody activities. PMID- 17350739 TI - Toward a conceptual framework of instrumental antisocial decision-making and behavior in youth. AB - This paper reviews and organizes relevant theory and research toward a conceptual framework of instrumental antisocial decision-making and behavior in youth. To date, social cognitive study of the development of youth antisocial functioning has largely focused on response patterns (e.g., cognitive responses to aversive cues). Though instrumental decision making is paid significant attention in research on adult criminality, there exists no framework by which youths' goal driven behavioral decisions that are made in pursuit of antisocial motives and interests may be understood. This is a problem in that lessons from research on children and adolescents suggest that there are meaningful differences in structure, phenomenology and function of subtypes of antisocial behavior (instrumental versus reactive). The absence of such a model may account, at least in part, for why the study of instrumental antisocial behavior in youth remains relatively limited. PMID- 17350738 TI - Intra-articular anesthesia and knee muscle response. AB - BACKGROUND: Many receptors located within the intra-articular knee structures contribute to the neuromuscular responses of the knee. The purpose was to compare the automatic postural response induced by a perturbation at the foot before and after an intra-articular injection of a local anesthetic (bupivicaine), after a saline (sham) injection, and after no intra-articular injection (control) in the knee. METHODS: Muscle onset latencies and automatic response magnitudes for the vastus medialis, vastus lateralis, biceps femoris, medial hamstrings, tibialis anterior, and gastrocnemius were measured using electromyography (EMG) when anteriorly directed perturbations were applied to the feet of 30 subjects. All subjects then received a lidocaine skin injection followed by: an intra-articular bupivicaine injection (treatment group); an intra-articular saline injection (sham group); or no injection (control group), depending on their randomized group assignment. The perturbation tests were then repeated. FINDINGS: Muscle onset latencies and automatic response magnitudes did not change as a result of the intra-articular injections. Latencies were significantly greater for the vastus medialis and vastus lateralis when compared to the medial hamstrings, biceps femoris and tibialis anterior (P<0.001). Automatic response magnitudes for the tibialis anterior were significantly greater than those of the hamstrings, which were greater than those of the quadriceps (P<0.001). INTERPRETATION: There were no differences in muscle response when anteriorly directed perturbations were applied to the foot with or without an injection of local anesthetic in the knee. Intra-articular receptors were either unaffected by the anesthetic or the extra-articular receptors or receptors of the other joints were able to compensate for their loss. PMID- 17350740 TI - Personality and chronic fatigue syndrome: methodological and conceptual issues. AB - Among clinical psychologists, consulting physicians, scientific researchers and society in general an image has emerged of patients with chronic fatigue syndrome (CFS) as perfectionist, conscientious, hardworking, somewhat neurotic and introverted individuals with high personal standards, a great desire to be socially accepted and with a history of continuously pushing themselves past their limits. The aim of this article is to (a) give a concise review of the main recent studies on personality and CFS, (b) address the major methodological problems in the study of personality in CFS and (c) discuss some of the conceptual assumptions that seem to limit the research on personality and CFS. The results of the reviewed studies range from no evidence of major differences between the personalities of patients with CFS and controls, to evidence of severe psychopathology and personality disorder in patients with CFS. Although personality seems to play a role in CFS, it is difficult to draw general conclusions on the relation between personality and CFS. It is argued that this is partially due to the diversity and heterogeneity in study methods, patient populations, control groups and CFS case definitions. Personality should be regarded as an important factor to be studied in CFS. However, additional studies are needed, not focusing exclusively on personality disorder, or personality considered on a general trait level. In recent developments in personality research, the continually evolving life narrative that makes sense of, and gives direction to, an individual's life is also regarded as an important aspect of personality. New insights into personality and CFS might be gained by systematically studying the self-narratives of patients with the syndrome. PMID- 17350741 TI - Safety evaluation of water extracts of Toona sinensis Roemor leaf. AB - The purposes of this study were to evaluate the safety of water extracts of Toona sinensis Roemor leaf (TSL-1). The mutagenic properties of TSL-1 was investigated using the Ames test, and no mutagenicity was found toward all tester strains (Salmonella typhimurium TA98, TA100, TA102 and TA1535). In the acute oral toxicity study, a single limit dose of 5000 mgTSL-1/kg bw was given to male and female ICR mice, then observed for a 14-day period. In the subacute study, TSL-1 was administered as oral daily dose of 1000 mg/kg bw/day for 28 days. The results showed no acute lethal effect at a maximal tested dose of 5000 mg/kg bw TSL-1 in male and female mice. The subacute toxicity showed the oral administration of 1000 mg/kg bw for consecutive 28 days was safe in male mice. TSL-1 treated female mice showed decreases of food intake and kidney relative weight in acute oral toxicity test, and decreases of body weight gain, food intake and lung relative weight in subacute toxicity trial. However, no remarked toxic effects were found in the biochemical and histopathological parameters of TSL-1 treated female mice. These effects whether related to the major components or other ingredients in TSL 1 need to elucidate in the further studies. PMID- 17350742 TI - Study on the mechanism of trichlorfon-induced inhibition of progesterone synthesis in mouse leydig tumor cells (MLTC-1). AB - Trichlorfon, a widely used organophosphorus pesticide, has been reported to disrupt reproductive function in humans. However, the mechanisms have not been clearly elucidated. In the present study, mouse Leydig tumor cells (MLTC-1) was used to evaluate the effect of trichlorfon on progesterone synthesis. After the various concentrations of trichlorfon treatment (0, 0.04, 0.2, 1, 5 or 25 micromol/l) for 24h, the progesterone production presented a dose-dependent decrease in the presence of some stimulators such as human chorionic gonadotrophin (hCG), cholera toxin (CT) or forskolin. However, the levels of intracellular cAMP remained unaltered, which suggested that trichlorfon suppressed steroidogenesis occurred after PKA activation along cAMP/PKA pathway. Moreover, trichlorfon suppressed the expression of the steroidogenic acute regulatory protein (StAR) mRNA and protein, and also profoundly inhibited the activity of P450 side chain cleavage enzyme (P450scc), rather than 3beta hydorxysteroid dehydrogenase (3beta-HSD). The suppressive expression of P450scc mRNA and protein further accounted for the inhibitory action of trichlorfon on steroidogenesis. These results indicated that trichlorfon suppressed progesterone synthesis in MLTC-1 cells, at least in part, via inhibiting StAR expression and P450scc activity. PMID- 17350743 TI - Impending cardiac arrest due to mitral-valve stenosis and left atrial "ball valve" thrombus. PMID- 17350744 TI - The neurobiological characteristics of rapid eye movement (REM) sleep are candidate endophenotypes of depression, schizophrenia, mental retardation and dementia. AB - Animal models are a promising method to approach the basic mechanisms of the neurobiological disturbances encountered in mental disorders. Depression is characterized by a decrease of REM sleep latency and an increase of rapid eye movement density. In schizophrenia, electrophysiological, tomographic, pharmacological and neurochemical activities are all encountered during REM sleep. Mental retardation and dementia are characterized by rather specific REM sleep disturbances. Identification of the genetic support for these abnormalities (endophenotypes) encountered during REM sleep could help to develop specific treatments. PMID- 17350745 TI - Expert opinion: vaginal aplasia: creation of a neovagina following the Creatsas vaginoplasty. AB - Vaginal aplasia is an uncommon congenital anomaly which is usually diagnosed as part of the Mayer-Rokitansky-Kuster-Hauser syndrome. The appropriate management of the anomaly includes the creation of a neovagina, and various surgical or non surgical techniques have been described. Among them the Creatsas modification of Williams vaginoplasty is an operative technique which involves the following surgical steps: Under general anesthesia, and after cutting the hymen with the use of diathermy, a U-shaped incision is made in the vulva extending across the perineum and up to the medial side of the labia to the level of the external urethral meatus, being 4cm lateral to it. The tissues are mobilized and a first layer of interrupted sutures is put between the inner skin margins using absorbable material with the knots lying inside the creating neovagina. A second layer of the same material is used to approximate the subcutaneous fat and the perineal muscles and finally, the external skin is sutured with absorbable interrupted stitches. The Creatsas vaginoplasty is simple, safe and highly effective, as its application in a large number of patients has been followed by excellent results, with the creation of a satisfactory neovagina (length 10-12 cm, width 5 cm) in 98% of patients. PMID- 17350746 TI - Effect of metformin on IGF-1 and IGFBP-1 levels in obese patients with polycystic ovary syndrome. PMID- 17350747 TI - Determination of metformin transfer across the human placenta using a dually perfused ex vivo placental cotyledon model. AB - OBJECTIVE: The aim of the study was to quantify and characterize metformin transfer across the human placenta using an ex vivo placental perfusion model. STUDY DESIGN: Placentas were obtained from vaginal deliveries or caesarean sections and selected cotyledons were cannulated and dually perfused. Metformin (1 microg/ml) and a permeability reference marker, antipyrine (50 microg/ml), were added to the maternal circulation. Each perfusion experiment was conducted for 180 min while samples were taken from the maternal and fetal compartments. The integrity and viability of the placenta were determined by measuring the flow rates, fetal artery inflow pressure, and hCG production during the experiments. RESULTS: Six complete experimental set-ups were completed. The maternal-fetal transport rates for metformin and antipyrine were 10.61+/-2.85% and 30.98+/ 5.62%, respectively. The clearance index, calculated as the ratio between the permeabilities of metformin and antipyrine, was 0.34+/-0.05. CONCLUSION: The results indicate that metformin is able to cross the mature human placenta; thus, fetal exposure must be considered when treating pregnant women with metformin. PMID- 17350748 TI - LCA: a decision support tool for environmental assessment of MSW management systems. AB - Life cycle assessment (LCA) can be successfully applied to municipal solid waste (MSW) management systems to identify the overall environmental burdens and to assess the potential environmental impacts. In this study, two methods used for current MSW management in Phuket, a province of Thailand, landfilling (without energy recovery) and incineration (with energy recovery), are compared from both energy consumption and greenhouse gas emission points of view. The comparisons are based on a direct activity consideration and also a life cycle perspective. In both cases as well as for both parameters considered, incineration was found to be superior to landfilling. However, the performance of incineration was much better when a life cycle perspective was used. Also, landfilling reversed to be superior to incineration when methane recovery and electricity production were introduced. This study reveals that a complete picture of the environmental performance of MSW management systems is provided by using a life cycle perspective. PMID- 17350749 TI - Editorial comment on: systematic assessment of the ability of the number and percentage of positive biopsy cores to predict pathologic stage and biochemical recurrence after radical prostatectomy. PMID- 17350750 TI - Systematic assessment of the ability of the number and percentage of positive biopsy cores to predict pathologic stage and biochemical recurrence after radical prostatectomy. AB - OBJECTIVES: We hypothesized that the number and/or percentage of positive cores, proxies of tumor volume, could improve the ability to predict pathologic stages and/or biochemical recurrence (BCR). To test this hypothesis, we examined radical retropubic prostatectomy (RRP) data from three centers on two continents. MATERIAL AND METHODS: Clinical data from men undergoing RRP at three different institutions were used to predict pathologic stages and BCR. Univariable and multivariable logistic analyses and Cox regression analyses were used. Predictive accuracy (PA) was assessed with the area under the receiver operating characteristics curve estimates, which were subjected to 200 bootstraps to reduce overfit bias. The statistical significance of PA gains was assessed with the Mantel-Haenszel test. RESULTS: The number and the percentage of positive cores were independent predictors of virtually all pathologic stage outcomes and of BCR. In PA analyses, the percentage of positive cores improved the PA of pathologic stage predictions and of BCR predictions between 0.06% and 1.49%. Conversely, the number of positive cores improved the PA of pathologic stage predictions and of BCR predictions between 0.36% and 1.14%. CONCLUSIONS: The information derived from biopsy cores is important and can improve the ability to predict pathologic stage and BCR. It appears that the percentage of cores is most helpful in stage predictions. Conversely, the number of cores appears to improve mostly BCR predictions. Consideration of both variables might not be helpful because of the similarity of information they encode. PMID- 17350751 TI - Editorial comment on: systematic assessment of the ability of the number and percentage of positive biopsy cores to predict pathologic stage and biochemical recurrence after radical prostatectomy. PMID- 17350752 TI - The interaction and cellular localization of HSP27 and ERbeta are modulated by 17beta-estradiol and HSP27 phosphorylation. AB - Recently, we identified heat shock protein 27 (HSP27) as an estrogen receptor beta (ERbeta) associated protein that acts as a co-repressor of estrogen signaling and serves as a biomarker of atherosclerosis. In this study, we sought to further characterize the subcellular interaction of HSP27 and ERbeta, as well as explore the factors that may modulate this interaction. In vitro we determined that phosphorylated HSP27 is retained in the cytoplasm after treatment with 17beta-estradiol and to a lesser extent with heat shock. Under all experimental conditions ERbeta was found to be slightly more abundant in the cytoplasm compared to the nucleus. HSP27 and ERbeta associate in both the cytoplasm and nucleus, however, co-localization studies reveal that in the presence of 17beta estradiol, a significant portion of this interaction occurs outside of the nucleus. These data highlight an extranuclear interaction between ERbeta and HSP27 that may be of potential importance in modulating estrogen signaling. PMID- 17350753 TI - Extragonadal LH/hCG action--not yet time to rewrite textbooks. AB - Gonadotropins are indispensable in both sexes in the regulation of gonadal sex steroid production and gametogenesis. In addition to their well-established classical actions, numerous recent publications have indicated the presence and function of luteinizing hormone/chorionic gonadotropin receptors (LH/hCG-R) in a variety of extragonadal tissues. However, the physiological significance of such effects has remained unclear. We have generated two genetically modified mouse models, one with excessive production of hCG and the other with targeted disruption of LH/hCG-R gene, and used them to address the functions of LH and hCG. Numerous gonadal and extragonadal phenotypes were found in the models with the two extremes of LH/hCG action. However, when the extragonadal effects were scrutinized in greater detail, they all appeared to arise through modification of gonadal function, either through enhanced or inhibited response to LH/hCG stimulation. Hence, further evidence is needed before the extragonadal LH/hCG-R expression can be considered functionally significant. PMID- 17350754 TI - Feasibility investigation of oily wastewater treatment by combination of zinc and PAM in coagulation/flocculation. AB - Poly-zinc silicate (PZSS) is a new type of coagulant with cationic polymer synthesized by polysilicic acid and zinc sulfate. It has been used in several sorts of wastewaters treatment, but not used in oily wastewater treatment. In this study, we investigated the coagulation/flocculation of oil and suspended solids in heavy oil wastewater (HOW) by PZSS and anion polyacrylamide (A-PAM). The properties of PZSS cooperated with A-PAM were compared with PAC and PFS in dosages, PAMs amount, settling time, pH value and flocs morphology. The results showed that PZSS was more efficient than PAC and PFS. Under the optimum experimental conditions of coagulation/flocculation (dosage: 100mg/L, A-PAM dosage: 1.0mg/L, settling time time: 40min and pH 6.5-9.5), more than 99% of oil was removed and suspended solid value less than 5mg/L by using PZSS cooperated with A-PAM, which could satisfy the demands of the pre-treatment process for HOW to be reused in the steam boiler or recycled into the injecting well. PMID- 17350755 TI - Simultaneous sorption and desorption of Cd, Cr, Cu, Ni, Pb, and Zn in acid soils II. Soil ranking and influence of soil characteristics. AB - In Part I of this paper we reported, for each of 11 acid soils, the rankings of six metals according to their sorption from solutions containing all six, and according to their retention under desorption conditions. Here, we analyse the same data from a different perspective: for each metal, we rank the soils by their capacities to sorb and retain it as reflected by soil/solution distribution coefficients K(d100) measured using starting solutions containing 100mgL(-1) of each metal. We also ranked the soils for overall heavy metal sorption and retention capacities using Kaplan's compound measure K(dSigma), and we investigated the influence of soil characteristics on K(d100) and K(dSigma100) values. Overall capacity for sorption of heavy metals was positively related to HOM, kaolinite and Fe oxides contents, and negatively related to CEC and to vermiculite and haematite contents. Overall capacity for retention of heavy metals was positively related to HOM and kaolinite contents, and negatively related to CEC and vermiculite content. The good correlation between K(dSigma100)(sorption) and the first component extracted in a principal components analysis of K(d100)(sorption) values, and between K(dSigma100)(retention) and the first component extracted in a principal components analysis of K(d100)(retention) values, supports the adequacy of K(dSigma) as a measure of the overall capacity of a soil to sorb or retain heavy metals. PMID- 17350756 TI - Depressed mood and lateralized prefrontal activity during a Stroop task in adolescent children. AB - Negative affective style and depressive disorders share a common pattern of brain activation asymmetry in adults, characterized by reduced left relative to right prefrontal activation. It is not clear whether a similar pattern of asymmetry is related to depressive mood state during the period of adolescence, an important stage of emotional and brain development. We correlated Beck Depression Inventory (BDI) scores from 16 adolescents with prefrontal, anterior cingulate, and amygdala activity during functional magnetic resonance imaging (FMRI) of the Stroop Interference task. Depressed mood correlated positively with activity in the left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate gyrus, and negatively with activity in the right DLPFC. When interpreted from a compensatory recruitment perspective, findings suggest that affective lateralization in adolescents is consistent with that seen in adulthood. PMID- 17350757 TI - Hydrogen peroxide-induced Ca2+ responses in CNS pericytes. AB - OBJECTIVE: The aims of the present study were to elucidate the interaction of reactive oxygen species (ROS) and Ca(2+) response in central nervous system (CNS) pericytes. METHODS: The intracellular Ca(2+) concentration was measured using fluorescent Ca(2+) indicator, fura-2, in cultured CNS pericytes. RESULTS: Hydrogen peroxide evoked a dose-dependent increase in cytosolic Ca(2+), which was completely inhibited by catalase. Removal of external Ca(2+) or addition of nicardipine (1 microM) during application of hydrogen peroxide did not affect Ca(2+) response. Incubation of the cells in Ca(2+) free solution did not abolish but slightly reduced Ca(2+) response by hydrogen peroxide. Ca(2+) response to hydrogen peroxide was not altered by the depletion of intracellular Ca(2+) by thapsigargin (1 microM). Pretreatment of the cells with tyrosine kinase inhibitor genistein (100 microM) or tyrphostin A47 (30 microM) significantly reduced Ca(2+) increase by hydrogen peroxide. CONCLUSIONS: These results indicate that hydrogen peroxide evokes Ca(2+) increase predominantly by release from intracellular Ca(2+) store, which may be regulated by tyrosine kinases. PMID- 17350758 TI - Significant correlation between plasma and CSF anticholinergic activity in presurgical patients. AB - Previous studies have suggested a possible link between cognitive impairment and anticholinergic burden as reflected by high serum anticholinergic activity (SAA). Thus, we hypothesized a close relationship between anticholinergic activity in cerebral spinal fluid (CSF) and blood. However, it has never been convincingly demonstrated that peripheral anticholinergic activity correlates with central anticholinergic levels in presurgical patients. Therefore, anticholinergic activity was measured in blood and CSF from 15 patients with admission scheduled for urological surgery to compare peripheral and central anticholinergic level. Blood and CSF probes were taken after routine premedication and before spinal anesthesia. Anticholinergic activity was determined by competitive radioreceptor binding assay for muscarinergic receptors. Correlation analysis was conducted for peripheral and central anticholinergic levels. The mean anticholinergic levels were 2.4+/-1.7 in the patients' blood and 5.9+/-2.1 pmol/mL of atropine equivalents in CSF. Interestingly, the anticholinergic activity in CSF was about 2.5-fold higher than in patients' blood. A significant linear correlation was detected between blood and CSF levels. Therefore we conclude that SAA levels adequately reflect central anticholinergic activity. When patients receiving or not receiving anticholinergic medication were compared, anticholinergic activity tended to increase in blood and CSF after receiving anticholinergic medication > or =4 weeks (p>0.05). PMID- 17350759 TI - Multipotent stem cells from the young rat inner ear. AB - The terminal mitosis of hair cells (HCs) and supporting cells (SCs) in mammalian cochlea occurred during middle embryonic development. Most hearing loss results from the incapacity of the cochlear sensory epithelium to replace lost hear cells. Deafness due to hair cells loss is normally irreversible. The present study showed that cells acutely dissociated from the cochlea of young rat, cultured with EGF and FGF2, developed into otospheres that showed expression of nestin and incorporation of 5'-Bromo-2-deoxyuridine (BrdU). The subcultured otospheres maintained for up to 10 passages. In addition, the cochlea sphere derivatives contributed to a variety of cell types. They were found to differentiate to neuron, glia, hair cell and supporting cell phenotypes. The results suggest that the young rat inner ear cells have self-renewal capability and multipotent differentiation potential. This work raises the possibility that inner ear cells in the early post-natal rat have the character of pluripotent stem cells and might be a source for cell replacement therapy in the inner ear. PMID- 17350760 TI - 5-HT2 modulation of AY-9944 induced atypical absence seizures. AB - We investigated the role of 5-HT(2A) and 5-HT(2C) receptors in atypical absence seizures (AAS) induced by trans-1,4-bis[2-chloro-benzylaminomethyl] cyclohexane, dihydrocholoride (AY-9944). The total duration and number and mean duration of the spontaneous bursts of slow spike-and-wave discharges (SSWD) that characterize the AY model were measured using electrocorticographic (ECoG) recordings in freely moving animals. In a randomized counterbalanced dose response design, rats were treated with either the 5-HT(2A) agonist 1-[2,5-dimethoxy-4-iodophenyl]-2 aminopropane (DOI, 0.5, 1 or 2 mg/kg), the 5-HT(2C) preferring agonist m chlorophenylpiperazine (mCPP, 1, 2, or 4 mg/kg), the 5-HT(2A) antagonist ketanserin (2.5 or 5 mg/kg), or vehicle. DOI significantly reduced the total duration and number of SSWD. In contrast, mCPP had no effect on total duration or number of SSWD. Ketanserin exacerbated the number of SSWD at 2.5 mg/kg but produced mixed results at 5.0 mg/kg. However, none of the treatments affected the mean SSWD duration. These data support the hypothesis that 5HT(2A) receptors are involved in the pathology of experimental atypical absence seizures. PMID- 17350761 TI - Etomidate and propofol-hyposensitive GABAA receptor beta3(N265M) mice show little changes in acute alcohol sensitivity but enhanced tolerance and withdrawal. AB - Gamma-aminobutyric acid-A (GABAA) receptors are ligand-gated ion channels comprised of subunits from several classes (alpha, beta, gamma, delta). Recent studies have clearly demonstrated that the functional properties of GABAA receptors are altered following chronic ethanol administration that could provide the molecular basis for the previously proposed role of these receptors in ethanol tolerance and dependence. Because the subunit composition of GABAA receptors determines receptor pharmacology, the present study was devoted to assess if the behavioral sensitivity after acute and chronic ethanol exposure depends on beta3-containing GABAA receptors. In the present study, we used knock in mice harboring a point mutation (N265M) in the second transmembrane region of the beta3 subunit of the GABAA receptor in order to study acute and chronic behavioral effects of ethanol. More specifically, we tested tolerance to loss of righting reflex (LORR) and the development of withdrawal signs after chronic ethanol exposure using ethanol vapor chambers. Our results show that the beta3(N265M) mutation does not play a major modulatory role of acute ethanol induced LORR. However, following repeated LORR testing, enhanced tolerance to the intoxicating effects of ethanol was observed--a finding which was unrelated to the pharmacokinetics of ethanol as both genotypes had the same blood alcohol concentrations following repeated LORR testing. In addition, following chronic alcohol vapor exposure, mouse mutants displayed increased handling-induced convulsions during withdrawal. The results of the present study suggest that the alcohol effects abolished by the beta3(N265M) mutation do not play a dominant role in acute alcohol intoxication but influence ethanol tolerance and withdrawal. PMID- 17350762 TI - Modulation of persistent nociceptive inputs in the anterior pretectal nucleus of the rat. AB - The anterior pretectal nucleus (APtN) participates in nociceptive and antinociceptive mechanisms. Drugs were injected into the ventral APtN to evaluate how intrinsic mechanisms interact in the nucleus during persistent allodynia produced by a surgical incision in a rat hind paw. Naloxone (1 and 10 ng/0.08 microl), methysergide (0.037 and 3.7 ng/0.08 microl) or atropine (0.1 and 10 ng/0.08 microl) increased the allodynia. The effect of methysergide was intensified by naloxone or atropine, the effect of atropine was intensified by naloxone or methysergide, but the effect of naloxone was not changed by methysergide or atropine. DAMGO (1.5 microg/0.08 microl), oxotremorine (5 microg/0.08 microl) or serotonin (5 microg/0.08 microl) reduced the allodynia. The effect of DAMGO was less intense in methysergide-treated rats but was not changed in atropine-treated rats, the effect of serotonin was not changed by naloxone or atropine, and the effect of oxotremorine was not changed by naloxone or methysergide. Baclofen (150 ng/0.08 microl) increased, whereas phaclofen (300 ng/0.1 microl) reduced the allodynia. Bicuculline (50 ng/0.08 microl) increased the incision pain, while muscimol (50 ng/0.08 microl) did not change it. Phaclofen was inhibited by methysergide but was unchanged by atropine. The effect of DAMGO was reduced by phaclofen (100 ng/0.1 microl). We interpret these results as indicative that noxious inputs utilize cholinergic and serotonergic pathways in the vAPtN for the activation of descending pain control mechanisms, the serotonergic pathway being under the control of GABAergic neurons which, in turn, are modulated negatively by opioid nerve terminals. PMID- 17350763 TI - PLC-beta 3 signals upstream of PKC epsilon in acute and chronic inflammatory hyperalgesia. AB - While protein kinase C epsilon has been shown to contribute to acute and chronic mechanical hyperalgesia, its upstream signaling pathway has received little attention. Since phospholipase C can signal to PKC epsilon and has been implicated in nociceptor sensitization, we tested if it is upstream of PKC epsilon in mechanisms underlying primary mechanical hyperalgesia. In the rat, the PKC epsilon-dependent mechanical hyperalgesia and hyperalgesic priming (i.e., a form of chronic latent enhanced hyperalgesia) induced by carrageenan were attenuated by a non-selective PLC inhibitor U-73122. A lipid mediator of PLC signaling, l-alpha-lysophosphatidylcholine produced dose-dependent mechanical hyperalgesia and hyperalgesic priming, which was attenuated by EAVSLKPT, a selective PKC epsilon inhibitor. However, U-73122 did not attenuate hyperalgesia induced by psi epsilon RACK, a selective PKC epsilon activator. Antisense to PLC beta 3 isoform, which was found in small-diameter dorsal root ganglion neurons, also attenuated carrageenan-induced acute and chronic-latent hyperalgesia. These studies support the suggestion that PLC-beta 3 is an important upstream signaling molecule for PKC epsilon-mediated acute and chronic inflammatory pain. PMID- 17350764 TI - Immunodiagnosis of current fasciolosis in sheep naturally exposed to Fasciola hepatica by using a 2.9 kDa recombinant protein. AB - A 2.9 kDa recombinant-Fasciola hepatica protein (FhrAPS) was employed to estimate the prevalence of fasciolosis in sheep maintained under field conditions. For this purpose, 340 samples with known status in relation to fasciolosis by using a direct-ELISA and the coprological sedimentation were used. These samples were analysed by using an indirect-ELISA (iELISA) and the FhrAPS recombinant protein and excretory/secretory antigens (FhES) of this trematode. Current fasciolosis (CF) was named when results were positive to antigenemia and/or coprology. Out of 198 sheep with current fasciolosis, 68% were positive to the FhrAPS-ELISA test and 53% to the FhES. We observed 14% of the CF-neg sheep were positive to the FhrAPS, whereas this percentage was 52% with the FhES. A significant correlation between FhrAPS and current fasciolosis was obtained (r2=0.513, p=0.001). We concluded that the FhrAPS provides a more suitable antigen than FhES for developing field trials to know the prevalence of early and current fasciolosis. PMID- 17350765 TI - Efficacy of vaccination in preventing giardiasis in calves. AB - The objective of this study was to evaluate the efficacy of a vaccine in the prevention of Giardia duodenalis infection in calves. Six 2-week old calves were vaccinated subcutaneously with a sonicated G. duodenalis trophozoite vaccine. Six 2-week old control calves received a subcutaneous injection of sterile phosphate buffered-saline mixed with adjuvant. Injections were repeated after 28 days. Eleven days after the second injection, calves were challenged orally with 1x10(5) purified G. duodenalis cysts from a naturally infected calf. Throughout the study, fecal samples were collected at regular intervals and examined for the presence of G. duodenalis cysts. Blood samples were collected weekly until G. duodenalis challenge and bi-weekly following challenge. Calves were euthanized 14 days after challenge and G. duodenalis trophozoites within the small intestines were enumerated. Serum antibody titers were significantly higher in vaccinated compared to non-vaccinated calves. Vaccinated calves tended to excrete more G. duodenalis cysts in their feces than non-vaccinated calves. The number of trophozoites in the small intestine was not different between vaccinated and non vaccinated calves. Changes consistent of moderate enteritis were found in the intestines of one vaccinated and one non-vaccinated calf. Despite a serological immune response following vaccination, this vaccine was not efficacious in preventing giardiasis or reducing cyst shedding in calves. PMID- 17350766 TI - Caution on the potential usefulness of statins in neuropsychiatric diseases. PMID- 17350767 TI - Zonular fibers, multimolecular composition as related to function (elasticity) and pathology. AB - Zonular fibers (ZF) play an important role in accommodation. With the rapid increase over the last decade of the oldest part of the population in industrialized countries, age-dependent loss of accommodation became an increasingly important problem. It appeared therefore interesting to review old and recent literature on ZF, their composition, structure and pathological alterations. By comparing former and recent reports it appeared to us, that several previous reports were not sufficiently taken in consideration for the understanding of the rheological properties of ZF. Elastin and proteoglycans glycosaminoglycans were reported previously as constituents of ZF. Their presence besides fibrillin, the major constituent, helps to explain the rheological properties of these fibers, and especially their elasticity and its age- and pathology-dependent decline. Our review points also to some of the major problems, which remain to be addressed by future experiments. PMID- 17350768 TI - Possible role of nucleotide correlations between human exon junctions. AB - There is ample evidence that prediction of human splice sites can be refined by analyzing the nucleotides surrounding splice sites. This could mean that exon nucleotides over splice sites harbour information for the splicing process in addition to the coding information to specify aminoacids. We analyzed the correlations among the nucleotides lying at the end and at the beginning of all the consecutive human exons to seek relationships among the nucleotides. We have divided the sequences taking into account the phase of interruption. Even though exon sequences are involved in the coding function, we found phase-dependent, specific correlations in the area of exon junctions. These regularities do not give rise to specific motifs, but rather to a phase-specific nucleotide context that could contribute to define the splice site or aid the splicing machinery to join the exon ends. Results provide further evidence that accurate selection of human splice sites likely requires the contribution of exon regulatory sequences. PMID- 17350769 TI - Genetic diversity of Hungarian canine distemper virus strains. AB - To achieve proper diagnosis of dogs based on acute clinical symptoms and poorly preserved field samples taken from animals that died due to canine distemper (CD), a new differential diagnostic test has been developed based on polymerase chain reaction (PCR). In this study, more than 150 samples collected from dogs showing respiratory, gastrointestinal and neurological signs suggesting canine distemper virus (CDV) infection were examined. The samples consisted of urine, blood and nasal swabs collected from clinically ill patients, sent to our laboratory by clinicians from various veterinary clinics throughout Hungary. Various organs collected during the necropsy of dogs with pathological changes that suggested CDV infection were also included. Three distinct PCRs were designed. For diagnostic purposes, a primer pair specific to a 409 bases-long segment within the conservative part of the large polymerase region (L) of the CDV genome was designed. Using this test, out of the 150 analyzed samples, 46 (30.66%) proved to be positive for CDV, indicating that CDV still represents a high risk to the canine population in Hungary. For the phylogenetical analysis, a primer pair that completely encompasses the hemagglutinin (H) gene of the CDV genome was designed. The amplicons of this region were sequenced in both directions using the appropriate primers. Our results indicate that several different CDV genotypes are currently present in Hungary. Nine of the analyzed Hungarian strains turned out to belong to the so-called Arctic group of CDVs, and were most closely related to non-European strains from North America, China and Greenland, as well as to the phocine distemper virus 2 (PDV-2) isolated from Baikal seals (Phoca sibirica). One of the Hungarian strains showed high similarity to other European isolates from Denmark, Germany, Italy and Turkey, as well as to other isolates from geographically more distant regions, such as the USA. Three Hungarian strains seem to join a new cluster that is formed by only a couple of strains, one isolated from a mink in Denmark, and another from a dog in North America. Using a third set of primers, a restriction fragment length polymorphism (RFLP) assay has also been designed for the fast and reliable differentiation of the wild-type CDVs from the vaccine strains. PMID- 17350770 TI - Specific identification of Gallibacterium by a PCR using primers targeting the 16S rRNA and 23S rRNA genes. AB - Gallibacterium was recently established as a new genus including organisms previously reported as Pasteurella anatis, [Actinobacillus] salpingitidis and avian Pasteurella haemolytica-like organisms. The aim of the present study was to develop a PCR method allowing unambiguous identification of Gallibacterium. PCR primers positioned in the 16S rRNA (1133fgal) and 23S rRNA (114r) genes were defined and their specificity was subsequently tested on 122 strains. Twenty-five of the strains represented all of the presently available 15 phenotypic variants of Gallibacterium from different geographical locations, 22 other strains represented other poultry associated bacterial species or bacteria which could pose a differential diagnostic problem including members of the families Pasteurellaceae, Enterobacteriaceae and Flavobacteriaceae, and finally 75 Gallibacterium field strains isolated from Mexican chicken egg-layers. Specific amplicons were generated in all 100 Gallibacterium strains tested, whereas none of the non-Gallibacterium strains tested positive. Correct identification was confirmed by hybridization with the Gallibacterium specific probe GAN850. Two internal amplification control strategies were successfully incorporated into the PCR assay, one based on amplification of the house-keeping gene rpoB (sharing target DNA) and another based on addition of trout DNA (foreign target DNA) and amplification with beta-actin specific primers. In conclusion, the described PCR assay enables specific identification of Gallibacterium and will thus stand as a strong alternative to the present diagnostic methods. PMID- 17350771 TI - Presence and diversity of the beta-lactamase gene in cat and dog staphylococci. AB - Staphylococci are part of the normal microflora of humans and animals and some are potential pathogens that have become resistant to almost all known antibiotics. Despite the widespread reports of penicillin resistance in cat and dog staphylococci, the mechanism underlying penicillin resistance has not been examined. This study was aimed at investigating the molecular basis of resistance to penicillin in cat and dog staphylococcal isolates that showed phenotypic resistance to beta-lactam antibiotics. An 861 bp fragment of the structural blaZ gene which codes for beta-lactamase production in staphylococci was amplified by polymerase chain reaction (PCR) and the products were sequenced. Sequenced fragments were analysed by protein signature typing and sequences were compared to published blaZ sequences of human and bovine staphylococcal strains held in a public database. Four known protein signature types (1, 3, 5 and 6) and one new type (12) were identified in this study. When sequences were compared with published blaZ sequences, gene phylogenetic analysis revealed three major groups. The four variants of beta-lactamases types (A, B, C and D) belonged to each major group except for types A and D which were both in group II. These findings confirm that the blaZ gene is responsible for beta-lactamase production leading to subsequent resistance to beta-lactam antibiotics in feline and canine staphylococci and that the gene shows similar diversity and relatedness as found with blaZ sequences obtained from human and bovine staphylococci. PMID- 17350772 TI - Oxygen tension during in vitro culture of bovine embryos: effect in production and expression of genes related to oxidative stress. AB - In vitro bovine embryos production and quality was evaluated in two culture systems, which utilize different oxygen tension. After IVM/IVF presumptive zygotes were cultured in either one of the two systems. The culture systems evaluated were-high O2: SOFaaci medium and culture for 7 d under 5% CO2 in air, at 39 degrees C in the presence of cumulus cells (control); low O2: SOFaaci medium and culture for 7 d under 5% CO2 and 5% O2 at 39 degrees C. In low O2 system the zygotes were denuded by successive pipetting before being transferred to culture medium, while in the high O2 zygotes kept the cumulus cells that remained after IVF. Cleavage rates were evaluated 48 h post-insemination (hpi) and the blastocyst rates at D6 and D7 post-insemination (pi). From both groups a total of 94 expanded blastocysts, from D7 of culture, were fixed and stained with aceto-orcein to evaluate cell numbers. Seven pools of 15 embryos from each treatment were frozen for gene expression evaluation. The abundance of transcripts for genes related to oxidative stress, superoxide dismutase (Mn-SOD), catalase, gluthatione peroxidase (GPX) and for embryo quality, interferon-tau (IFN-tau) were determined using a semi-quantitative RT-PCR. Cleavage rate was similar (P>0.05) for both groups. The blastocyst rate at D6 pi was greater (P<0.05) in the group cultured under low O2 tension (37.4%) than in the high O2 tension (21.9%). However, blastocyst rate and total cell number at D7 were similar (P>0.05) between groups. No change (P>0.05) in transcript amount between treatments was observed for GPX, catalase and IFN-tau genes. However, the relative abundance of transcripts for Mn-SOD gene was greater (P<0.05) for embryos cultured in high O2 tension system. The results suggest that bovine embryos can be cultured either in SOFaaci medium under greater O2 tension in the presence of cumulus cells, or in SOFaaci medium under less O2 tension, without affecting embryo production or quality. PMID- 17350773 TI - Alterations in the human brain in menopause. AB - In a series of studies we showed that menopause in women causes alterations not only in the neuronal expression of estrogen receptors (ER) alpha and beta, but also in local estrogen production in several brain areas and in the rate of neuronal metabolism. Although such changes are clearly brain region-specific, there seems to be no evidence at present for a decrease in neuronal metabolic rate. On the contrary, an increase in the neuronal metabolic activity and in the level of ERalpha in postmenopausal women was noted. In the supraoptic nucleus (SON) that is a major source of plasma arginine-vasopressin (AVP) we found that neuronal metabolic activity as judged from the Golgi apparatus and cell size was markedly enhanced in women after menopause accompanied by an increase in ERalpha and a decrease in ERbeta. Similar changes were noted in the medial mamillary nucleus and in the hippocampus that are involved in the regulation of learning and memory. Recently we aimed at determining whether in addition to the canonical ERalpha and ERbeta, estrogen receptor splice variants lacking entire exons may also be involved in the menopause-associated changes in the human brain. We detected del. 2 (missing exon 2), del. 4 (lacking exon 4), del. 7 (exon 7 absent) and MB1 (deletion of 168 nucleotides in the exon 1) in the frozen hippocampal tissue of 6 women (46, 52, 59, 64, 77 and 83 years of age). No age-related changes were observed for the mentioned splice forms in women of this group. PMID- 17350774 TI - Tibolone for prevention and treatment of postmenopausal osteoporosis. AB - Tibolone has been widely accepted as remedy for vasomotor symptoms and for prevention of bone loss. Studies over the past 25 years have documented its effects on bone mineral density in younger and older women. Tibolone reduces bone turnover substantially (about the same amount as hormone therapy). Increases in bone mineral density (BMD) accompany this reduction in bone turnover, but like all other antiresorptive therapies, reduction in fracture risk (i.e. 50%) is always greater than would be predicted from BMD change. Finally, as with hormone therapies, dosage reductions have been prompted by new evidence of low dosage efficacy and concern over dose-related side effects. Solid evidence has now emerged from large, dose-ranging studies that the 1.25mg tibolone dosage is adequate for preservation of BMD and for reduction of fracture risk. Now that fracture efficacy has been added to the list of tibolone's documented bone benefits, physicians must consider this in the overall risks and benefits of its use. PMID- 17350775 TI - The influence of noise type and level upon stochastic resonance in human audition. AB - The present study examined the extent to which noise type and fine differentiations in noise level produced improvements in auditory threshold via the mechanism of stochastic resonance. Participants' thresholds for a sinusoidal signal (2.0 kHz) were estimated using a three interval forced choice task. These measures were obtained in quiet, in the presence of Gaussian noise, and in the presence of uniform (flat spectrum, zero-mean amplitude distribution) noise. The noises were presented at several levels from audible to inaudible (0.0 to -35.0 dB/Hz). The present results show that thresholds improved by a small, but significant, amount for noise levels just below subjects' thresholds and that these improvements are not due solely to a simple summation of power between the signal and the noise. In addition, a subset of subjects showed larger and significant threshold increases at very low noise levels (-30.0 to -35.0 dB/Hz). The outcomes suggest that either Gaussian or uniform noise produces equivalent threshold improvements, SR may already be nearly optimized in persons with normal hearing, and that the maximum benefit possible from SR occurs over a narrow range of noise levels. PMID- 17350776 TI - Effects of auditory pathway anatomy and deafness characteristics? Part 2: On electrically evoked late auditory responses. AB - The purpose of this study was to distinguish the effects of different parameters on latencies of wave N1, wave P2, and inter-peak interval N1-P2 of electrical late auditory responses (ELARs). ELARs were recorded from four intra-cochlear electrodes in fourteen adult HiRes90K cochlear implant users who had at least three months of experience. The relationship between latencies and stimulation sites in the cochlea was characterized to assess the influence of the auditory pathway anatomy on ELARs, i.e., whether the speed of neural propagation varies according to the place that is activated in the cochlea. Audiograms before implantation, duration of deafness, and psychophysics at first fitting were used to describe the influence of deafness characteristics on latencies. The stimulation sites were found to have no effect on ELAR latency and, while there was no influence of psychophysics on latency, a strong relationship was shown with duration of deafness and the pre-implantation audiogram. Thus, ELAR latency was longer for poorer audiograms and longer durations of deafness and this relationship appeared to be independent of stimulation parameters such as stimulation site. Comparison between these findings and those from the equivalent study on EABR waves IIIe and Ve latency [Guiraud, J., Gallego, S., Arnold, L., Boyle, P., Truy, E., Collet, L., 2007. Effects of auditory pathway anatomy and deafness characteristics? (1): On electrically evoked auditory brainstem responses. Hear. Res. 223 (1-2), 48-60] shows that, while ELAR and EABR latencies are related with parameters that reflect the integrity of the auditory pathway, ELAR latency is less dependent on stimulation parameters than EABR latency. PMID- 17350777 TI - Isolation and identification of antiplasmodial sesquiterpene lactones from Oncosiphon piluliferum. AB - Oncosiphon piluliferum (Asteraceae) is used traditionally to treat a variety of ailments, mainly fevers. This prompted the screening of this plant for antiplasmodial properties. The dichloromethane extract of the aerial parts of the plant showed activity in vitro against the chloroquine-sensitive (IC(50) 2.6microg/ml) and the chloroquine-resistant (IC(50) 3.1microg/ml) strains of Plasmodium falciparum. Through conventional chromatographic techniques and bioassay-guided fractionation, sesquiterpene lactones of the germacranolide and eudesmanolide type displaying significant in vitro antiplasmodial activity (IC(50) values ranging from 0.4 to 4.4microg/ml) were isolated and identified by spectroscopic data. In addition, the cytotoxic effects of the active compounds against Chinese Hamster Ovarian (CHO) cells were evaluated and the compounds were found to be toxic to mammalian cells at similar concentrations. Structure activity relationships were assessed. PMID- 17350778 TI - Genetic analysis of 15 STR loci on Chinese Tibetan in Qinghai Province. AB - We report allele frequencies and statistical parameters of 15 short tandem repeats (STR) loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) determined in 850 unrelated individuals of Chinese Tibetan, an ethnic group residing in Qinghai Province, China. We observed 155 alleles with allele frequencies ranging from 0.0006 to 0.5682. The distribution of these observed genotypes were not significantly different from the expected distribution according to Hardy Weinberg equilibrium. The forensic parameters from the data showed high values. In conclusion, the 15 STR loci are useful for forensic analysis, paternity tests for Tibetans in the region, and population genetic studies. PMID- 17350779 TI - Allele frequencies for nine STR loci in Ovambo population using AmpFlSTR Profiler Kit. AB - Allele frequencies for the nine short tandem repeat (STR) loci D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317, and D7S820 were investigated in 195 unrelated Ovambo (Bantus) population from Namibia. AmpFlSTR Profiler Kit was employed for amplification. For each locus, 6-19 alleles were observed. Comparison between Ovambo population data and that of other African populations was performed. AmpFlSTR Profiler detection system is a useful tool for individual identification in Ovambo population. PMID- 17350780 TI - 16 Y chromosomal STR haplotypes in Japanese. AB - A total of 1079 Japanese males were typed for the following 16 Y chromosomal short tandem repeat (Y-STR) markers: DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385, DYS393, DYS391, DYS439, DYS635, DYS392, Y GATA H4, DYS437, DYS438 and DYS448 using an AmpFlSTR(R) Yfiler PCR Amplification kit (Applied Biosystems). A total of 950 haplotypes for the 16 Y-STR markers were detected and, of these, 886 haplotypes were unique. The most frequent haplotype was found in 22 Japanese males. The haplotype diversity was 0.9992, indicating a high potential for differentiating between male individuals. There were 10 haplotypes with no allele detected at the DYS448 marker. Thus, the presence of such atypical haplotypes should be noted, when DNA typing results obtained from degraded DNA samples and/or DNA mixture samples from more than one male individual are being interpreted. PMID- 17350781 TI - Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age. AB - The association between inflammation and neuropsychiatric symptoms in old age is generally accepted but poorly understood. The purpose of this study was to examine whether inflammation precedes depressive symptoms and cognitive decline in old age, and to identify specific inflammatory pathways herein. We measured serum C-reactive protein (CRP) and lipopolysaccharide-induced production of Interleukin (IL)-1beta, IL-6, Tumor Necrosis Factor (TNF)-alpha, IL-1 receptor antagonist (ra), and IL-10 levels in 85-year-old participants free from neuropsychiatric symptoms at baseline (n=267). Participants were prospectively followed for depressive symptoms (Geriatric Depression Scale) and cognitive functioning (Mini Mental State Examination) from 85 to 90 years. Higher baseline CRP levels preceded accelerated increase in depressive symptoms (p<0.001). A higher production capacity of the pro-inflammatory cytokine IL-1beta preceded a greater increase of depressive symptoms (p=0.06), whereas that of its natural antagonist IL-1ra preceded a smaller increase of depressive symptoms (p=0.003). There was no relation of CRP, IL-1beta, and IL-1ra with cognitive decline. Our findings show that in old age inflammatory processes contribute to the development of depressive symptoms but not cognitive decline. A high innate IL 1ra to IL-1beta production capacity reflects a better ability to neutralize inflammation and may therefore protect against depressive symptoms. PMID- 17350782 TI - Anterior knee pain. AB - Anterior knee pain is a common complain in all ages athletes. It may be caused by a large variety of injuries. There is a continuum of diagnoses and most of the disorders are closely related. Repeated minor trauma and overuse play an important role for the development of lesions in Hoffa's pad, extensor mechanism, lateral and medial restrain structures or cartilage surface, however usually an increase or change of activity is referred. Although the direct relation of cartilage lesions, especially chondral, and pain is a subject of debate these lesions may be responsible of early osteoarthrosis and can determine athlete's prognosis. The anatomy and biomechanics of patellofemoral joint is complex and symptoms are often unspecific. Transient patellar dislocation has MR distinct features that provide evidence of prior dislocation and rules our complication. However, anterior knee pain more often is related to overuse and repeated minor trauma. Patella and quadriceps tendon have been also implicated in anterior knee pain, as well as lateral or medial restraint structures and Hoffa's pad. US and MR are excellent tools for the diagnosis of superficial tendons, the advantage of MR is that permits to rule out other sources of intraarticular derangements. Due to the complex anatomy and biomechanic of patellofemoral joint maltracking is not fully understood; plain films and CT allow the study of malalignment, new CT and MR kinematic studies have promising results but further studies are needed. Our purpose here is to describe how imaging techniques can be helpful in precisely defining the origin of the patient's complaint and thus improve understanding and management of these injuries. PMID- 17350783 TI - Patients perceptions of information about risks at cardiac surgery. AB - OBJECTIVE: The aim was to describe the patients' own experiences of risk information in connection with cardiac surgery and it's outcome. METHODS: Questionnaires were answered prior to and 8 weeks after cardiac surgery. Data were analysed using qualitative content analysis. Patients in the intervention group (n=55) received standard information and a newly written extended information brochure about risks in connection with cardiac surgery. Patients in the control group (n=44) only received standard information. RESULTS: Three categories emerged: attitude towards information, deficiencies and advantages of the information and concerns related to cardiac surgery. Patients in both groups pointed out the importance of information when they were put on the waiting list. Patients in the control group missed information about complications and some patients thought that their complications were caused by maltreatment. Patients having complications in the intervention group were more understanding about their situation. CONCLUSION: Much can be done for the patients on their path from diagnosis and being accepted for cardiac surgery and throughout the treatment period regarding the provision of information. PRACTICE IMPLICATIONS: If patients become carefully and thoroughly informed by the health care professionals, they are more satisfied and better prepared if complications occur. PMID- 17350784 TI - Impaired Fas-induced apoptosis of T lymphocytes in patients with abdominal aortic aneurysms. AB - OBJECTIVE: Homeostasis of the immune system is maintained by apoptotic elimination of potentially pathogenic autoreactive lymphocytes. Emerging evidence shows that Fas-mediated apoptosis is impaired in activated lymphocytes from patients with autoimmune disease. The aim of this work was to assess apoptosis mediated by the cell death receptor Fas in peripheral T lymphocytes from patients with abdominal aortic aneurysms (AAA). METHODS: The apoptotic pathway was triggered by anti-Fas monoclonal antibodies in cultured and activated peripheral T-cell lines from 20 AAA patients with control groups of 15 patients with aortic atherosclerotic occlusive disease (AOD) and 25 healthy individuals. Cell survival and death (apoptosis) rate were assessed. RESULTS: Cross-linkage of Fas receptor exerted a strong apoptotic response on T cells from AOD patients and healthy controls, but a much less pronounced effect on T cells from AAA patients. The evaluation of cell survival rate showed a significantly higher percentage in AAA group (98.9% +/- 10.3%) than in the AOD subjects (58.9% +/- 15.2%) or the healthy group (59.4% +/- 12.9%; P < .001). Apoptosis assessment by annexin V and propidium iodide staining and flow cytometry showed similar results. The defect in AAA group was not due to decreased Fas expression, since Fas was expressed at normal levels. Moreover, it specifically involved the Fas system because cell death was induced in the normal way by methylprednisolone. Complementary DNA sequencing identified no causal Fas gene mutation, but two silent single nucleotide polymorphisms with higher frequency were found in the AAA group. CONCLUSIONS: Fas-induced apoptosis in activated T cells from AAA patients is impaired. This may disturb the normal down-regulation of the immune response and thus provide a new insight into possible mechanisms and routes in the pathogenesis of AAA. PMID- 17350785 TI - Curative surgery after neoadjuvant chemotherapy in metastatic poorly differentiated neuroendocrine carcinoma. PMID- 17350786 TI - [Cutaneous manifestations as the initial presentation of Wegener's granulomatosis]. AB - INTRODUCTION: Wegener's granulomatosis is a rare systemic vasculitis, characterized by involvement of the upper airways, lungs and kidneys; other organs may also be affected. Cutaneous lesions occur frequently during the disease course but seldom as its initial presentation. Digital necrosis and splinter hemorrhages of fingernails are described, but very rarely. CASE: We report the case of a 55-year-old man presenting multisystemic Wegener's granulomatosis with mucosal and cutaneous involvement at initial presentation: tongue and labial ulcers, digital necrosis, splinter hemorrhages of fingernails, and purpura. The PR3-ANCA titer was high. Imaging and the histological findings of both cutaneous and renal biopsies suggest a diagnosis of Wegener's granulomatosis. He was treated with prednisone, cyclophosphamide, and cotrimoxazole. Cutaneous and mucosal symptoms disappeared 6 weeks after treatment began. DISCUSSION: The particularity of this case is the association of four separate cutaneous manifestations of Wegener's granulomatosis - two of them very rare - as the initial presentation of this multisystemic disease. PMID- 17350787 TI - [New insights into the pathogenesis of ANCA-positive vasculitides]. AB - Recent studies provided new insights into the pathogenesis of vasculitides associated with antineutrophil cytoplasm antibodies (ANCA). They yield more information about the pathogenic role of ANCA, the initiation of the immune response against proteinase 3, the expression of ANCA target antigens on neutrophil surfaces, endothelial damage and the mechanisms of vasculitis associated with propylthiouracil. The pathogenic role of antimyeloperoxidase antibodies has been established in vitro and in vivo in animal models and in human. A pathogenic role for antiproteinase 3 antibodies has not yet been clearly established in vivo although it is well documented in vitro. PMID- 17350788 TI - [Animals parasites that cause human diseases]. PMID- 17350789 TI - [Alcohol, tobacco and colorectal adenomas and cancer. Case-control study in a population with positive fecal occult blood tests]. AB - OBJECTIVE: To analyze the associations between lifestyle factors and colorectal adenomas or cancers in a population 50-74 years old. METHOD: The study population underwent colonoscopy after positive fecal occult blood test in Health examination centers of the French general health insurance. The two sets of cases (n= 674 cancers, n=2618 adenomas) were compared with controls (n=5456). Associations between risk of colorectal disease and health data (mainly tobacco and alcohol consumption, physical activity, obesity, and laboratory test results) were analyzed with logistic regression models to estimate odds ratios. RESULTS: The probability of colorectal cancer or adenoma was statistically associated with age (60 years or older in men and women). A significant relation between these diseases was observed with smoking (in both smokers and ex-smokers) and with alcohol consumption, with odds ratios above 1.30. The other risk factors studied were not significantly associated with these colorectal diseases. CONCLUSION: This result provides still more evidence of the need for actions against these risk behaviors. PMID- 17350790 TI - [Evidence-based medicine for the national ranking examination: response to critics]. PMID- 17350792 TI - [Prevention of cervical cancer (II): prophylactic HPV vaccination, current knowledge, practical procedures and new issues]. AB - Despite the considerable success of early screening for prevention of cervical cancer, Pap smears have not fulfilled the hopes that it would lead to a large scale reduction of this cancer's incidence. Screening appears to be useful for a tiny portion of the world population, although a relatively large portion must put up with its limitations and disadvantages. Human papilloma viruses (HPV) 16 and 18 are responsible for two thirds of all cervical cancers worldwide. The condylomata (condyloma acuminatum), or genital warts, induced by HPV 6 and 11 are frequent among the young and difficult to manage. The extent and burden of HPV infection are considerable, as is the psychological and emotional impact of the diseases associated with it. Because cancer of the cervix is the final consequence of chronic HPV infection, it can be prevented by vaccination. A prophylactic vaccine to protect against the precancerous and cancerous lesions associated with HPV should save lives, reduce expensive diagnostic and therapeutic interventions, and have substantial individual and collective benefits. Clinical trials of anti-HPV vaccines for the prevention of cervical cancer and condyloma have shown remarkable results and an efficacy unequaled in the history of vaccination against infectious diseases. Vaccine efficacy has been shown only in young girls never exposed to the virus and only for the lesions associated with the specific viral types in the vaccine. Preliminary data indicate that the vaccination is effective in women who have previously eliminated naturally the virus. It has no therapeutic effects on existing lesions or in healthy virus carriers. Practical questions remain to be resolved. If the vaccination is left to individual initiative and vaccination coverage is insufficient, there will be no perceptible reduction in the frequency of cervical cancer. Vaccination policies will not be identical in poor countries, where the disease represents one of the leading causes of mortality among women, and in the rich countries, where screening programs have considerably reduced the frequency of this cancer. Current planning calls for the introduction of systematic vaccination of young girls aged 9-15 years, with progressive "catch-up" vaccination of the cohorts of young women aged 16-26 years. Nonetheless mathematical models and immunogenicity results indicate a possible benefit for individual vaccination of adults. This approach must still be assessed in the clinical trials underway. Because the vaccine does not protect against all types of HPV associated with cervical cancer, screening must be continued according to the conditions currently set. Vaccination and screening, which are complementary and synergistic, now constitute the new standards for prevention of this disease. PMID- 17350791 TI - [What type of adjuvant chemotherapy should be proposed for the initial treatment of glioblastoma?]. AB - Carmustine wafers (Gliadel) and temozolomide (Temodal) were recently approved for initial management of glioblastoma. Gliadel) is a polymer wafer containing carmustine. These wafers are designed to be placed in the surgical cavity after glioblastoma resection to deliver local chemotherapy. This treatment is intended for tumors for which gross total resection is possible. Temozolomide is administered concomitantly with radiotherapy for six weeks followed by six cycles of adjuvant temozolomide (EORTC 26981, also known as "Stupp's protocol"). Temozolomide administered according to this protocol produced a median survival benefit of 2 months in glioblastomas, and carmustine a similar benefit in high grade gliomas. The two-year survival rate was 26.5% with radiotherapy plus temozolomide compared with 10.4% with radiotherapy alone. In patients with complete resection, two-year survival reached 38%. These two new treatments are essentially intended for patients younger than 70 years and with a Karnofsky index>70. Ongoing studies are evaluating the possible value of combining these two treatments. PMID- 17350793 TI - [Microscopic polyangiitis]. AB - Microscopic polyangiitis was initially considered a "microscopic" form of polyarteritis nodosa and was not definitively distinguished from it until the Chapel Hill nomenclature (1994). Microscopic polyangiitis is a systemic necrotizing vasculitis of small vessels. Its typical clinical manifestations are rapidly progressive glomerulonephritis and alveolar hemorrhage. Other possible symptoms resemble those encountered in polyarteritis nodosa. Microscopic polyangiitis belongs to the group of ANCA-associated vasculitides, and 75-80% of patients have pANCA to myeloperoxidase (MPO). Anti-MPO ANCA pathogenicity has been established in animal models, and a recent report describes transplacental transfer of these antibodies in humans, resulting in pulmonary hemorrhage and renal involvement in the newborn. Patients with no poor prognostic factors, as defined by a five-factor score, can be treated with corticosteroids alone, with immunosuppressants added only in case of treatment failure. Patients with one or more poor prognostic factors must receive a combination of corticosteroids and immunosuppressants, mainly intravenous pulsed cyclophosphamide, with plasma exchange as an adjuvant therapy for those with severe renal involvement. Once remission is achieved, maintenance therapy can replace cyclophosphamide by azathioprine or methotrexate. Biological therapies are under evaluation. The remission rate is above 80% with these regimens, and the relapse rate is around 30% at 5 years, lower than for Wegener's granulomatosis. PMID- 17350794 TI - Studies on the region involved in the transport activity of Escherichia coli TolC by chimeric protein analysis. AB - Gram-negative bacteria possess the outer membrane protein TolC which acts as an exit duct across the outer membrane. However, the region involved in the transport activity of TolC has remained unclear. We analyzed this region by creating chimeric TolCs. First, we expressed the genes for TolCs of Vibrio parahaemolyticus (vp-tolC) and Salmonella typhimurium (sal-tolC) in Escherichia coli. The levels of sequence identity in the mature region of VP-TolC/EC-TolC and Sal-TolC/EC-TolC with maximum matching are 43% and 90%, respectively. We found that the transport activity of VP-TolC was weak compared with that of TolC of E. coli (EC-TolC) although the transport activity of Sal-TolC was similar to that of EC-TolC. A comparison of the sequence of the three tolCs showed that the sequence around the periplasmic region covering Asn-188 to Lys-214 of EC-TolC is lowly identical to that of VP-TolC although the region of EC-TolC is almost identical to that of Sal-TolC. We think, therefore, that the region covering Asn-188 to Lys 214 of EC-TolC may have an important role to express its transport activity in E. coli. To examine the possibility, we divided the region of EC-TolC into three and exchanged the gene for each portion with that of vp-tolC. These mutant ec-tolCs were expressed in E. coli and the activity of each chimeric TolC was measured. The results showed that the portion covering Val-198 to Lys-214 of EC-TolC is deeply involved in the transport activity. PMID- 17350795 TI - Lycopene activity against chemically induced DNA damage in Chinese hamster ovary cells. AB - Lycopene is a natural pigment synthesized by plants and microorganisms, and it is mainly found in tomatoes. It is an acyclic isomer of beta-carotene and one of the most potent antioxidants. Several studies have demonstrated the ability of lycopene to prevent chemically induced DNA damage; however, the mechanisms involved are still not clear. In the present study, we investigated the antigenotoxic/antimutagenic effects of lycopene in Chinese Hamster Ovary Cells (CHO) treated with hydrogen peroxide, methylmethanesulphonate (MMS), or 4 nitroquinoline-1-oxide (4-NQO). Lycopene (97%), at final concentrations of 10, 25, and 50 microM, was tested under three different protocols: before, simultaneously, and after the treatment with the mutagens. Comet and cytokinesis block micronucleus assays were used to evaluate the level of DNA damage. Data showed that lycopene reduced the frequency of micronucleated cells induced by the three mutagens. However, this chemopreventive activity was dependent on the concentrations and treatment schedules used. Similar results were observed in the comet assay, although some enhancements of primary DNA damage were detected when the carotenoid was administered after the mutagens. In conclusion, our findings confirmed the chemopreventive activity of lycopene, and showed that this effect occurs under different mechanisms. PMID- 17350796 TI - The relation between symptom validity testing and MMPI-2 scores as a function of forensic evaluation context. AB - The association between scores on MMPI-2 scales and cognitive symptom validity test (SVT) failure was investigated in 127 criminal defendants evaluated for competency to stand trial, criminal responsibility, and drug dependence, and 141 personal injury and disability claimants. Results indicated that SVT failure was associated with exaggerated symptom presentation involving somatic complaints in civil litigants and more global exaggeration of psychopathology and somatic complaints in criminal defendants. Scores on the MMPI-2 Fake Bad Scale (FBS) were associated with SVT failure in both civil and criminal litigants, whereas scores on the MMPI-2 F(P) scale were associated with SVT failure in criminal defendants, but not in civil plaintiffs. These results support the utility of the FBS as an indicator of non-credible presentation of somatic and cognitive complaints in both civil and criminal forensic psychological assessments, and indicate that the lack of association between the MMPI-2 infrequency scales and SVT failure is limited to civil forensic settings. PMID- 17350797 TI - Race-specific norms: using the model of hypertension to understand issues of race, culture, and education in neuropsychology. AB - Development of appropriate and clear guidelines for proper use of neuropsychological tests among ethnic minorities is a current and significant challenge. Although development of race/ethnicity-specific norms is popular, it is also controversial. Some have argued that these norms will improve the sensitivity and specificity of neuropsychological measures in detecting cognitive impairment. However, two major arguments have surfaced that: (1) race-specific norms ignore underlying cultural and educational factors for which race serves as a proxy, and (2) setting "more lenient" cutoffs for impairment among ethnic minorities denies these groups needed services. In this paper, we argue that recent research on hypertension reveals a number of crucial lessons for neuropsychologists who are struggling with this issue. The model of hypertension is helpful in understanding issues of construct validity in neuropsychological testing, and is also helpful in revealing possible underlying causes of poor cognitive test performance for which race serves as a proxy. PMID- 17350798 TI - Members of a novel gene family, Gsdm, are expressed exclusively in the epithelium of the skin and gastrointestinal tract in a highly tissue-specific manner. AB - Gasdermin (Gsdm) was originally identified as a candidate causative gene for several mouse skin mutants. Several Gsdm-related genes sharing a protein domain with DFNA5, the causative gene of human nonsyndromic hearing loss, have been found in the mouse and human genomes, and this group is referred to as the DFNA5 Gasdermin domain family. However, our current comparative genomic analysis identified several novel motifs distinct from the previously reported domain in the Gsdm-related genes. We also identified three new Gsdm genes clustered on mouse chromosome 15. We named these genes collectively the Gsdm family. Extensive expression analysis revealed exclusive expression of Gsdm family genes in the epithelium of the skin and gastrointestinal tract in a highly tissue-specific manner. Further database searching revealed the presence of other related genes with a similar N-terminal motif. These results suggest that the Gsdm family and related genes have evolved divergent epithelial expression profiles. PMID- 17350799 TI - The gestational environment and Parkinson's disease: evidence for neurodevelopmental origins of a neurodegenerative disorder. AB - Parkinson's Disease (PD) is a degenerative neurological disorder that typically manifests symptoms in late adulthood, after loss of dopaminergic neurons in the nigrostriatal system. A lack of heritability for idiopathic PD has implicated adulthood environmental factors in the etiology of the disease. However, compelling evidence from animal models published within the past few years has shown that a range of environmental factors occurring during the perinatal period (including exposure to the common pesticides paraquat and maneb, organochlorine pesticides, and iron-enriched diet) and the prenatal period (including the pesticide maneb, cocaine, and the bacterial product LPS) can either directly cause a reduction in the number of dopamine neurons, or cause an increased susceptibility to degeneration of these neurons with subsequent environmental insults or with aging alone. In this review, these models are described for potential relevance in linking PD with the Fetal Basis of Adult Disease (FeBAD) hypothesis. Additionally, challenges in studying the neurodevelopmental basis of neurodegeneration experimentally and epidemiologically are presented. PMID- 17350800 TI - The relationship of self-injurious behavior and other maladaptive behaviors among individuals with severe and profound intellectual disability. AB - Participants were 101 individuals with self-injurious behavior (SIB) and severe or profound intellectual disability who were matched by gender, age, and level of intellectual disability to controls. Persons with SIB were more likely to exhibit the challenging behaviors of physical aggression, property destruction, sexually inappropriate behaviors and stereotypies when compared to controls, suggestive of co-occurring behaviors. Moreover, the maladaptive behavior of irritability, as assessed by the aberrant behavior checklist (ABC) was able to correctly classify 72.8% of the sample into their respective group memberships. Implications of these findings are discussed. PMID- 17350801 TI - Developmental lead (Pb) exposure reduces the ability of the NMDA antagonist MK 801 to suppress long-term potentiation (LTP) in the rat dentate gyrus, in vivo. AB - Chronic developmental lead (Pb) exposure increases the threshold and enhances decay of long-term potentiation (LTP) in the dentate gyrus of the hippocampal formation. MK-801 and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype impair induction of LTP. In addition, Pb exposure reduces presynaptic glutamate release and is associated with alterations in NMDA receptor expression. This study examined LTP in Pb-exposed animals challenged with a low dose of MK-801 to assess the sensitivity of this receptor to inhibition. Pregnant rats received 0.2% Pb acetate in the drinking water beginning on gestational day 16, and this regimen was continued through lactation. Adult male offspring maintained on this solution from weaning were prepared with indwelling electrodes in the perforant path and dentate gyrus. Several weeks later, input/output (I/O) functions were collected in awake animals before and after saline or MK-801 administration (0.05 mg/kg, s.c.). LTP was induced using suprathreshold train stimuli 60 min post-drug. Post-train I/O functions were reassessed 1 and 24 h after train delivery. Upon full decay of any induced LTP, drug conditions were reversed such that each animal was tested under saline and MK-801. I/O functions measured 1 and 24 h after train induction as well as immediate post-train responses revealed significant LTP of comparable magnitude that was induced in both control and Pb-exposed animals tested under saline conditions. In contrast, MK-801 reduced LTP in control but not in Pb exposed animals. The broadening of the excitatory postsynaptic potential evident in responses evoked by train stimuli is NMDA-dependent. Pb exposure attenuated the MK-801-induced reduction in area of this NMDA component by approximately 50%. These findings are consistent with other neurochemical and behavioural observations and suggest that up-regulation of postsynaptic NMDA receptors produces subsensitivity to the inhibitory effects of MK-801 on hippocampal LTP following chronic developmental Pb exposure. PMID- 17350802 TI - New insights about iron bioavailability inhibition by zinc. AB - OBJECTIVE: We measured the effects of lower and higher doses of zinc (Zn) given as an aqueous solution on the bioavailability of iron (Fe). METHODS: Fourteen healthy subjects received a solution with 0.5 mg of elemental Fe as ferrous sulfate given alone or with 0.59 mg of Zn as zinc sulfate (molar ratio Zn:Fe 1:1). Fourteen days after they received a second solution with 10 mg of Fe given alone or with 11.71 mg of Zn (molar ratio Zn:Fe 1:1). Iron bioavailability was assessed by erythrocyte incorporation of iron radioisotopes (55)Fe and (59)Fe. RESULTS: No significant effect of Zn on Fe bioavailability was observed at lower doses; however, at higher doses Fe bioavailability was inhibited by 56% (P < 0.001, repeated measures analysis of variance). CONCLUSION: The inhibitory effect of Zn on Fe bioavailability depends on the total amount of both minerals present in the intestinal lumen. This fact should be considered when designing a supplementation program if Fe and Zn are to be provided together. PMID- 17350803 TI - Iron absorption from wheat flour: effects of lemonade and chamomile infusion. AB - OBJECTIVE: We measured iron bioavailability of meals based on wheat flour consumed by a vulnerable population in Latin America. METHODS: Bioavailability of iron (ferrous sulfate) from fortified noodles, noodle soup, noodle soup eaten with lemonade sweetened with panela (unrefined whole cane sugar), bread alone, and bread consumed with a chamomile infusion sweetened with panela was studied using the double isotopic method in 13 women. RESULTS: Iron bioavailabilities from bread, noodles, and noodle soup were not significantly different (7.4%, 6.3%, and 6.0%, respectively). Iron absorption from noodle soup was significantly higher when given with lemonade (11.0%) compared with absorption of the same meal without lemonade (P < 0.02) or with the absorption of noodles (P < 0.04). Iron absorption of bread given alone or with chamomile infusion sweetened with panela (8%) was not significantly different. CONCLUSION: Iron bioavailability of meals based on wheat flour, fortified with ferrous sulfate, is improved when given with lemonade. The consumption of this beverage may be an alternative to further increase the effectiveness of wheat flour fortification in preventing iron deficiency in low-income Latin American populations. PMID- 17350804 TI - Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice. AB - OBJECTIVE: Effective approaches should be established to prevent the onset of type 2 diabetes mellitus, which has been increasing in developed countries. The present study examined whether dietary supplementation with cacao liquor proanthocyanidins (CLPr) could prevent elevation of blood glucose levels in mice with diabetes mellitus and obesity. METHODS: C57BL/KsJ-db/db (db/db) diabetic obese mice and C57BL/KsJ-db/+m (db/+m) control mice were fed a diet containing 0% w/w CLPr (0% CLPr), 0.5% w/w CLPr (0.5% CLPr), or 1.0% w/w CLPr (1.0% CLPr) from age 3 wk to age 6 wk. Levels of blood glucose were measured at 4 and 5 wk of age. The animals were sacrificed and the levels of blood glucose and fructosamine were measured at 6 wk of age. RESULTS: The levels of blood glucose and fructosamine were higher in the db/db mice than in the db/+m mice fed a diet containing 0%, 0.5%, or 1.0% CLPr. In the db/+m mice, the levels of blood glucose or fructosamine were not significantly different across animals fed 0% CLPr, 0.5% CLPr, and 1.0% CLPr. In the db/db mice, however, a diet containing 0.5% or 1.0% CLPr decreased the levels of blood glucose and fructosamine compared with that containing 0% CLPr without significant effects on body weights or food consumption. CONCLUSION: Dietary supplementation with CLPr can dose-dependently prevent the development of hyperglycemia in diabetic obese mice. The dietary intake of food or drinks produced from cacao beans might be beneficial in preventing the onset of type 2 diabetes mellitus. PMID- 17350807 TI - Cognitive impairment in schizophrenia: clinical ratings are not a suitable alternative to neuropsychological testing. AB - Despite the fact that cognitive impairment rated with clinical rating scales has been shown to be a poor proxy for cognitive functioning measured with a performance-based assessment battery, studies are still using this approach to predict aspects of outcome in schizophrenia. In the current study 106 outpatients with chronic schizophrenia who had been stable both from a symptomatic and a medication perspective for a period of 6 months before study inclusion were investigated to assess the relationship between a clinical rating of cognitive impairment and the actual performance on neuropsychological tests. The cognitive component of the PANSS was compared to results from a neuropsychological test battery which was selected to cover domains known to be impaired in patients with schizophrenia. Correlations of the cognitive component of the PANSS with the individual neuropsychological tests were low. They ranged between 0.19 and 0.35. None of them was sufficiently high to indicate that the cognitive component of the PANSS adequately covers the cognitive dimension measured by the respective neuropsychological test. These data clearly show that clinical assessment of cognitive deficits by the PANSS is not a viable alternative to neuropsychological testing to obtain information about cognitive functioning in schizophrenia. PMID- 17350806 TI - SGA and measures for muscle mass and strength in surgical Vietnamese patients. AB - OBJECTIVE: This study compared the outcome of the Subjective Global Assessment (SGA) in preoperative surgical patients with objective measurements of muscle mass and strength and with biochemical data. A secondary aim was to test the influence of inflammatory activity on muscle strength. METHODS: Two hundred seventy-four consecutive patients who were admitted for elective major abdominal surgery were assessed using the SGA, anthropometry, muscle strength, and laboratory measurements (hemoglobin, protein, albumin, C-reactive protein, and lymphocytes). Normal values for midarm muscle circumference (MAMC) and handgrip strength were obtained in a healthy control group. For all other variables, normal values available for the Vietnamese population were used. RESULTS: Of 274 patients (151 men, 123 women) assessed, 61 (22.3%) were classified as SGA class A (well nourished), 97 patients (35.4%) as class B (moderately malnourished), and 116 patients (42.3%) as class C (severely malnourished). There were significant differences in age, body weight, percentage of weight loss, triceps skinfold thickness, MAMC, and serum albumin across the three SGA classes. Almost all patients rated class A had normal MAMC and handgrip strength. However, a large proportion of patients rated as B or C also had normal MAMC and handgrip strength (38% of men, 50% of women). Handgrip strength per square meter correlated with serum albumin (r = 0.278, P < 0.001) and this correlation persisted when handgrip strength was controlled for MAMC (r = 0.296, P < 0.001 in men; r = 0.237, P < 0.01 in women). CONCLUSION: The SGA correctly identifies patients with normal muscle mass and strength but a substantial number of patients rated SGA B or C have normal muscle mass and strength. Muscle strength is not only positively associated with muscle mass but also negatively with inflammatory activity. PMID- 17350808 TI - Processes controlling the transmission of bacterial pathogens in the environment. AB - Many pathogens in the environment can be transmitted to human populations and cause outbreaks and epidemics. Transmission is a multifactorial process influenced by the physiology of the pathogen as it exits its initial host, the mechanisms it uses for surviving outside the host, the physiology of the pathogen as it enters the next susceptible host and its ability to establish a successful infection. Few studies so far have focused on the processes responsible for modulating microbial survival in non-host environments and the transmission dynamics between infected and susceptible hosts, as well as the interplay between hosts. A better understanding of these mechanisms is thus necessary for predicting and preventing future outbreaks. PMID- 17350809 TI - Interactions of pyrrolobenzodiazepine dimers and duplex DNA from methicillin resistant Staphylococcus aureus. AB - Binding of two bactericidal pyrrolobenzodiazepine (PBD) dimers, SJG-136 and ELB 21, to genomic DNA from Staphylococcus aureus EMRSA-16 was investigated. Both agents cross-linked purified EMRSA-16 DNA. The more potent agent, ELB-21, had a greater capacity to cross-link DNA after incubation with intact cells than SJG 136. Extensive interstrand cross-linking at multiple sites on the EMRSA-16 genome was demonstrated by probing EcoRI-restricted DNA with mecA and 16S rDNA. Cross linking was again greater in DNA extracted from ELB-21-treated cells and was compatible with frequency analysis of preferred binding sequences in EMRSA-16 DNA. These studies support the premise that the potency of ELB-21 is due to efficient cell penetration and provide evidence that the antibacterial activity of PBD dimers results from cross-linking at specific genomic sites. PMID- 17350810 TI - History of medicine: our Hippocratic heritage. PMID- 17350811 TI - Absorption and metabolism of albendazole after intestinal ischemia/reperfusion. AB - Pathophysiological processes involving inflammatory response may affect absorption and biotransformation of some drugs, modifying their pharmacokinetic behaviour. Ischemia/reperfusion (I/R) injury has been used as a model for inflammatory processes. The aim of this work was to study the effect of intestinal I/R injury on the absorption and metabolism processes of one orally administered drug, albendazole that is anthelmintic drug, it undergoes intestinal bioconversion into albendazole sulfoxide by two enzymatic systems, cytochromes P450 (CYP450) and flavin-containing monooxygenase (FMO). Male Wistar rats were used to study the influence of I/R in the intestinal absorption and metabolism of albendazole, after 60 min of mesenteric occlusion and 30 min of reperfusion. The intestinal studies were performed in microsomal, and everted ring incubations. During in situ studies, the I/R group had faster disappearance of albendazole from the lumen. In addition, albendazole only appeared in blood samples of the I/R group, while albendazole sulfoxide appeared in both samples and was higher in the control group. These findings are supported by significant reductions of albendazole sulfoxide formation in intestinal everted ring assays and in microsomal incubations after the I/R process. Both metabolizing systems, CYP4503A and FMO, were affected by I/R. Our data indicate that I/R injury, considered as an inflammatory model, reduces absorption and metabolism processes of albendazole. PMID- 17350812 TI - Effects of ethanol/l-menthol on the dynamics and partitioning of spin-labeled lipids in the stratum corneum. AB - The interaction of ethanol as well as ethanol/L-menthol mixtures with the uppermost layer of epidermis, the stratum corneum, was investigated by electron paramagnetic resonance (EPR) spectroscopy utilizing spin-labeled analogs of androstanol (ASL), stearic acid (5-DSA) and methyl stearate (5-DMS). The EPR spectra of these spin probes structured in stratum corneum tissue of neonatal rat are characterized by the coexistence of two spectral components indicating the presence of two classes of spin labels with very different states of mobility. Probably, one class of spin labels is H-bonded to the polar surface of the membrane and another class corresponds to spin labels more deeply inserted in the hydrophobic core. EPR results showed that in the ethanol range 0-70% neither fluidity in stratum corneum membranes nor the relative fractions of these two components changes were observed. Instead, ethanol only caused a selective extraction of spin labels. The removal of the steroid ASL began at 30% ethanol, reaching extraction levels over 50% at ethanol concentrations of 60-70%, whereas the more hydrophobic 5-DMS was partially removed only with 70% ethanol. Addition of 5% L-menthol to the solvent containing 20% ethanol increases both the mobility and the fraction of those spin labels situated in the hydrophobic core (more mobile spectral component). Altogether, these findings suggest that the L-menthol stabilizes mainly in the central region of stratum corneum membranes attracting the membrane lipids and causing hydrogen bond ruptures in the polar membrane interface. PMID- 17350813 TI - Development, characterization and in vivo evaluation of benzocaine-loaded liposomes. AB - This study reports the development and in vivo evaluation of a liposomal formulation of the local anaesthetic benzocaine. Multi-lamellar (MLV) and small uni-lamellar (SUV) vesicles entrapping benzocaine were prepared using 50:50 w/w phosphatidylcholine-cholesterol as lipophilic phase and 50:50 v/v ethanol-water as hydrophilic phase. Liposome size, Zeta-potential, encapsulation efficiency and skin penetration properties were determined. Drug permeation from liposomal dispersions, as such or formulated in Carbopol gel, was evaluated through artificial lipophilic membranes and excised abdominal rat skin, whereas in vivo anaesthetic effect was tested on rabbits. Interestingly, addition of the drug into the hydrophilic phase, rather than into the lipophilic one, during liposome preparation enabled an improvement of the MLV's entrapment efficiency from 29.7% to 82.3%. On the other hand, sonication conditions to obtain SUV influenced size and polydispersity index of the vesicles and reduced the entrapment efficiency by about 30%. All liposomal-benzocaine formulations showed sustained release properties and a more intense anaesthetic effect than plain drug. Permeation experiments from drug solutions in gel containing the same amount of ethanol as in the liposomal formulations made it possible to exclude a possible enhancer effect of this solvent, at least when not used in liposomal formulations. MLV with the drug added into the hydrophilic phase gave the most effective formulation, showing a permeability coefficient value 2.5 times higher than that of the plain drug and allowing a significant improvement (P<0.01) not only of intensity but also of duration of anaesthetic effect of benzocaine. These results suggest that a suitably developed liposomal formulation of benzocaine can be of actual value for improving its clinical effectiveness in topical anaesthesia. PMID- 17350814 TI - beta-Sitosterol activates Fas signaling in human breast cancer cells. AB - beta-Sitosterol is the most abundant phytosterol. Phytosterols are enriched in legumes, oil seeds and unrefined plant oils as found in foods such as peanut butter, pistachios and sunflower seeds. beta-Sitosterol inhibits the growth of several specific types of tumor cells in vitro and decreases the size and the extent of tumor metastases in vivo. The effects of beta-sitosterol on the extrinsic apoptotic programmed cell death pathway in human breast MCF-7 and MDA MB-231 adenocarcinoma cells were examined, along with the extent of its incorporation into cellular membranes and its effects on cell growth, expression of Fas receptor pathway proteins, and caspase-8 activity. The results show that beta-sitosterol exposure promotes its enrichment in transformed cell membranes and significantly inhibits tumor cell growth. Concurrently, Fas levels and caspase-8 activity are significantly increased. These actions are specific, as expression of other proteins of the Fas receptor pathway, including Fas ligand, FADD, p-FADD and caspase-8, remain unchanged. These findings support the hypothesis that beta-sitosterol is an effective apoptosis-promoting agent and that incorporation of more phytosterols in the diet may serve a preventive measure for breast cancer. PMID- 17350815 TI - Patterns of chest wall kinematics during volitional pursed-lip breathing in COPD at rest. AB - BACKGROUND: Analysis of chest wall kinematics can contribute to identifying the reasons why some patients benefit from pursed-lip breathing (PLB). MATERIAL AND METHODS: We evaluated the displacement of the chest wall and its compartments, the rib cage and abdomen, by optoelectronic plethysmography (OEP), during supervised PLB maneuver in 30 patients with mild to severe chronic obstructive pulmonary disease (COPD). RESULTS: OEP showed two different patterns. A first pattern characterized the 19 most severely obstructed and hyperinflated patients in whom PLB decreased end-expiratory volumes of the chest wall and abdomen, and increased end-inspiratory volumes of the chest wall and rib cage. Deflation of the abdomen and inflation of the rib cage contributed to increasing tidal volume of the chest wall. The second pattern characterized 11 patients in whom, compared to the former group, PLB resulted in the following: (i) increased end-expiratory volume of the rib cage and chest wall, (ii) greater increase in end-inspiratory volume of the rib cage and abdomen, and (iii) lower tidal volume of the chest wall. In the patients as a whole changes in end-expiratory chest wall volume were related to change in Borg score (r(2)=0.5, p<0.00002). CONCLUSIONS: OEP helps identifying the reason why patients with COPD may benefit from PLB at rest. PMID- 17350816 TI - Young maternal age at delivery is associated with asthma in adult offspring. AB - OBJECTIVE: Some studies have shown an association between lower maternal age at delivery and increased asthma in children and young adults. It is unclear whether this represents an effect of maternal ageing or a protective effect of siblings. In a North-European population based study, we investigated whether mother's age at delivery was associated with risk for asthma and hay fever in adult offspring, taking into account relevant confounders. METHODS: A total of 16,190 subjects (74%) aged 23-54 yr answered a postal questionnaire in a follow-up of the European Community Respiratory Health Survey (ECRHS I). RESULTS: The associations of maternal age at delivery with hay fever, respiratory symptoms and diagnosed asthma were analysed using logistic regression, adjusting for household size, dwelling, parental education, centre, gender, adult hay fever, smoking, age and body mass index (BMI). The adjusted odds ratios (95% CI) for wheeze with breathlessness, wheeze without a cold and asthma in the offspring were 0.94 (0.90 0.99), 0.89 (0.86-0.94) and 0.92 (0.88-0.97), respectively, per 5 yr increase in maternal age. No heterogeneity between centres was found (p=0.84). The estimates remained similar in sub-sample analyses when adjusting for siblings, maternal smoking (n=3109) and for birth weight (n=1686). Hay fever was more common among those with the youngest and oldest mothers. CONCLUSIONS: In this large North European multi-centre study, asthma was less common with increasing maternal age. This effect was consistent between centres and persisted with adjustment for several potential confounders, suggesting that the association may possibly be explained by biological changes related to maternal ageing. PMID- 17350817 TI - Healthcare waste management: current practices in selected healthcare facilities, Botswana. AB - Healthcare waste management continues to present an array of challenges for developing countries, and Botswana is no exception. The possible impact of healthcare waste on public health and the environment has received a lot of attention such that Waste Management dedicated a special issue to the management of healthcare waste (Healthcare Wastes Management, 2005. Waste Management 25(6) 567-665). As the demand for more healthcare facilities increases, there is also an increase on waste generation from these facilities. This situation requires an organised system of healthcare waste management to curb public health risks as well as occupational hazards among healthcare workers as a result of poor waste management. This paper reviews current waste management practices at the healthcare facility level and proposes possible options for improvement in Botswana. PMID- 17350818 TI - Development of a new quality fair access best value performance indicator (BVPI) for recycling services. AB - Recycling schemes are being used worldwide to reduce the impact of municipal waste. Those using public funds are usually obliged to set performance indicators by which the standards of such schemes can be measured. In the UK, a set of statutory Best Value Performance Indicators (BVPI) must be reported annually, such as the Quality of Fair Access, which monitors the public's access to recycling facilities within 1000 m (known as BVPI 91). This work shows that BVPI 91, and performance indicators like it, quantify only very basic recycling services. A much more sensitive performance indicator is developed in this paper, labelled as the Maximum Practicable Recycling Rate Provision (MPRRP) achievable by a local authority. It indicates the percentage of local waste that could be reasonably recycled using the services provided, calculated on the basis of the average composition of the local waste, the local population coverage for collection of any materials, and nationally provided information stating how much of each material stream is generally suitable (practical) for recycling. Evidence for the usefulness of this new quantity is presented. Although this paper refers a particular performance indicator in the UK, its findings are applicable to all urban areas worldwide needing to monitor recycling service. Furthermore, the MPRRP could be used for planning purposes, and for determining the level of performance of an existing service, by comparing its predicted recycling rate to that actually obtained. Further work is now being carried out on this. PMID- 17350819 TI - Overoxidized polypyrrole film directed single-walled carbon nanotubes immobilization on glassy carbon electrode and its sensing applications. AB - In this paper, the films of overoxidized polypyrrole (PPyox) directed single walled carbon nanotubes (SWNTs) have been electrochemically coated onto glassy carbon electrode (GCE). Electroactive monomer pyrrole was added into the solution containing sodium dodecyl sulfate (SDS) and SWNTs. Then, electropolymerization was proceeded at the surface of GCE, and a novel kind of conducting polymer/carbon nanotubes (CNTs) composite film with the orientation of CNTs were obtained correspondingly. Finally, this obtained polypyrrole (PPy)/SWNTs film modified GCE was oxidized at a potential of +1.8 V. It can be found that this proposed PPyox/SWNTs composite film modified GCE exhibited excellent electrocatalytic properties for some species such as nitrite, ascorbic acid (AA), dopamine (DA) and uric acid (UA), and could be used as a new sensor for practical applications. Compared with previous CNTs modified electrodes, SWNTs were oriented towards the outside of modified layer by PPyox and SDS, which made the film easily conductive. Moreover, this proposed film modified electrode was more stable, selective and applicable. PMID- 17350820 TI - Functional organization of the medial frontal cortex. AB - The anterior cingulate cortex (ACC) and adjacent areas of the medial frontal cortex (MFC) have been implicated in monitoring behaviour and in detecting errors. Recent evidence, however, suggests that the ACC not only registers the occurrence of errors but also represents other aspects of the reinforcement history that are crucial for guiding behaviour. Other studies raise the possibility that dorsal MFC areas not only monitor behaviour but also actually control response selection, particularly when the task in hand is changing. Many decisions are made in social contexts and their chances of success depend on what other individuals are doing. Evaluation of other individuals is therefore crucial for effective action selection, and some ACC regions are implicated in this process. PMID- 17350821 TI - Loss of APAF-1 expression is associated with tumour progression and adverse prognosis in colorectal cancer. AB - The aim of this study was to determine the prognostic value of APAF-1 in colorectal cancer (CRC). Immunohistochemistry for APAF-1 was performed on a tissue microarray of 1015 mismatch-repair (MMR) proficient and 130 sporadic MLH1 negative CRCs. The association of APAF-1 with clinico-pathological features including 10-year survival time was analysed. Methylation specific PCR was performed on a subset of MMR-proficient and MLH1-negative CRC. Loss of APAF-1 was associated with advanced T stage (p-value=0.022), N stage (p-value=0.009), vascular invasion (p-value=0.001) and worse survival (p-value=0.017) in MMR proficient CRC. In MLH1-negative CRC, loss of APAF-1 was associated with metastasis (p-value=0.041), worse prognosis (p-value<0.001) and independently predicted shorter survival time (p-value<0.001). No methylation was found in the selected region of APAF-1. APAF-1 is a marker of tumour progression in MMR proficient CRC and an independent adverse prognostic factor in MLH1-negative CRC. PMID- 17350822 TI - Prognosis in patients with hepatocellular carcinoma correlates to mutations of p53 and/or hMSH2 genes. AB - Association of gene alterations and prognosis has not fully been elucidated in hepatocellular carcinoma (HCC). To clarify the relationship between p53 and hMSH2 mutations and prognosis, we analysed these mutations in 83 HCC cases and assessed their association with various clinicopathological factors. The 3-year disease free survival (DFS) or overall survival (OS) rates in HCC patients with p53 mutation and p53 wild/hMSH2 mutation significantly decreased compared with those without these mutations (14.3% and 37.5% versus 67.5% for DFS; 35.7% and 50.0% versus 96.4% for OS, respectively). In the multivariate analysis, categories by p53 and hMSH2 mutation status, and liver cirrhosis demonstrated statistical significances for DFS and OS. Moreover, the frequency of patients with p53 and/or hMSH2 mutations in intrahepatic metastasis (75.0%) was significantly higher than that in multicentric occurrence (14.3%). Thus, p53 and hMSH2 mutations will be useful for identifying subsets of HCC patients with poor prognosis. PMID- 17350823 TI - Should DPD analysis be required prior to prescribing fluoropyrimidines? AB - Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolic catabolism of chemotherapeutic agent 5-fluorouracil (5FU) and its derivatives, including capecitabine. Numerous genetic mutations have been identified in the DPD gene locus (DPYD), with a few key variants having functional consequences on enzymatic activity. Deficiencies in DPD activity have been shown to cause 5FU-treated cancer patients to experience severe drug-related toxicities, often requiring extensive medical intervention. We review the performance of assays that assess DPD and DPYD status, with an emphasis on the robustness for routine clinical applications. None of the current strategies are adequate to mandate routine DPD testing prior to starting a fluoropyrimidine-based therapy. However, further research and technological improvements will hopefully allow prospective identification of potentially toxic patients, in order to reduce the number of patients with severe, life-threatening side effects to 5FU treatment. PMID- 17350824 TI - Exonic, but not intronic polymorphisms of ESR1 gene might influence the hypolipemic effect of raloxifene. AB - Studies have shown that selective modulator of estrogen receptor raloxifene, exerts hypolipemic properties at least partially through estrogen receptor alpha activation. To test the hypothesis that polymorphisms of estrogen receptor alpha are associated with the influence of 6 months raloxifene treatment on serum lipids, two intronic (PvuII and XbaI), and one exonic polymorphism (P325P) were analyzed in 49 postmenopausal women, mean age 62.5+/-5.7 years. In all subjects, the total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were determined before and after 6 months of raloxifene treatment. We were unable to find any relationship between estrogen receptor alpha genotype and serum lipids at baseline. At the end of 6 months treatment with raloxifene, the mean decrease of total cholesterol and LDL cholesterol, independently of genotypes, was highly significant, but no influence on HDL and triglycerides concentrations was found. Neither the PvuII nor XbaI ESR1 gene polymorphisms were associated with the magnitude of lipid changes after 6 months treatment, whereas the subjects with non-CC genotype of P325P mutation had significantly lower total cholesterol and LDL cholesterol concentrations, and higher decline of total cholesterol (p<0.05). CONCLUSION: Our data suggest that exonic, but not intronic polymorphisms of estrogen receptor alpha gene might intensify the cholesterol lowering effect of raloxifene. PMID- 17350825 TI - Arundo donax L. reed: new perspectives for pulping and bleaching. 5. Ozone-based TCF bleaching of organosolv pulps. AB - Three selected alkali-based organosolv pulps (alkali-sulfite-anthraquinone methanol (ASAM), alkali-anthraquinone-methanol (organocell) and ethanol-soda) from agrofibre crop giant reed (Arundo donax L.) were bleached by an ozone-based TCF (totally chlorine- free) bleaching sequence AZE(R)QP (where A is an acidic pulp pre-treatment, Z is an ozone stage, (E(R)) is an alkaline extraction in the presence of reducing agent, Q is a pulp chelating, P is a hydrogen peroxide stage) without oxygen pre-bleaching, and compared with a conventional kraft pulp used as a reference. The different response on bleaching conditions within each bleaching stage was noted for all tested pulps. The pulp bleachability, in terms of brightness improvement or lignin removal per unit of applied chemicals, was found higher for the organocell pulp. The ASAM and ethanol-soda pulps showed the highest bleaching selectivity, expressed by viscosity loss per unit of lignin removed or brightness improved. The overall bleaching results of organosolv pulps were superior to kraft. PMID- 17350826 TI - Improved phytase production by a thermophilic mould Sporotrichum thermophile in submerged fermentation due to statistical optimization. AB - Culture variables affecting phytase production by a thermophilic mould Sporotrichum thermophile in submerged fermentation were optimized. Soluble starch, peptone, Tween-80 and sodium phytate were identified by Plackett-Burman design as the most significant factors to affect phytase production. The 2(4) full factorial central composite design of response surface methodology was applied for optimizing the concentrations of the significant variables and to delineate their interactions. Starch, Tween-80, peptone and sodium phytate at 0.4%, 1.0%, 0.3% and 0.3% supported maximum enzyme titres, respectively. An overall 3.73-fold improvement in phytase production was achieved due to optimization. When sodium phytate was substituted with wheat bran (3%), the phytase titre in the former was comparable with that in the latter. PMID- 17350827 TI - Lentinus edodes and Pleurotus species lignocellulolytic enzymes activity in submerged and solid-state fermentation of lignocellulosic wastes of different composition. AB - Lentinus edodes and Pleurotus species from various origins were compared for the first time for their ability to produce lignocellulolytic enzyme in solid-state (SSF) and submerged (SF) fermentation of various plant raw material. Fungi cultivation in identical culture conditions revealed wide differences among both species and strains of the same species. The yields of CMCase (62.3Uml(-1)), xylanase (84.1 U ml(-1)), FPA (5.9 U ml(-1)), and laccase (4103 Ul(-1)) are the best so far obtained with the strains of oyster mushrooms. The study pointed out that the nature of lignocellulosic material and the method of fungi cultivation are factors determining the expression of lignocellulolytic potential of fungi as well as the ratio of individual enzymes in enzyme complex. SSF of tree leaves is favorable for laccase and MnP secretion by the majority L. edodes and Pleurotus strains, whereas SF provides better production of hydrolytic enzymes. PMID- 17350828 TI - Pulping of holm oak wood. Influence of the operating conditions. AB - This paper reports on the influence of independent variables in the pulping of holm oak wood (Quercus ilex L.) [viz. temperature (135-195 degrees C), cooking time (30-90min) and soda concentration (10-20%)] on the yield, holocellulose content, alpha-cellulose content, brightness and viscosity of the resulting pulp. By using a central composite factorial design, equations relating each dependent variable to the different independent variables were derived that reproduced the experimental results for the dependent variables with errors less than 5-15% in all cases. The highest pulp yield (56.9%) was obtained with the lowest values of the operating variables. However, obtaining the optimum holocellulose content, alpha-cellulose content and viscosity (viz. 94.5%, 78.5% and 1395ml/g, respectively) entailed using values of the independent variables above their mean levels. Also, ensuring optimal brightness (viz. 24.3%) required using higher temperatures and soda concentrations. A compromise that saves equipment immobilized capital and about 25% of soda is using a soda concentration of 15% at 195 degrees C for 30min. The yield thus obtained differs by less than 29.5% from the highest level; also, the resulting holocellulose content, alpha-cellulose content and brightness differ by less than 12% from their respective optimum values. PMID- 17350829 TI - Adsorption of Cd(II) ions from aqueous solutions using activated carbon prepared from olive stone by ZnCl2 activation. AB - This study is aimed to remove Cd(II) ions from aqueous solutions by adsorption. As adsorbent, activated carbon prepared from olive stone, an agricultural solid by-product was used. Different activating agent (ZnCl(2)) amounts and adsorbent particle size were studied to optimize adsorbent surface area. The adsorption experiments were conducted at different parameters such as, adsorbent dose, temperature, equilibrium time and pH. According to the experiments results, the equilibrium time, optimum pH, adsorbent dosage were found 60 min, pH > 6 and 1.0 g/50 ml respectively. The kinetic data supports pseudo-second order model and intra-particle model but shows very poor fit for pseudo-first order model. Adsorption isotherms were obtained from three different temperatures. These adsorption data were fitted with the Langmuir and Freundlich isotherms. In addition, the thermodynamic parameters, standard free energy (DeltaG(0)), standard enthalpy (DeltaH(0)), standard entropy (DeltaS(0)) of the adsorption process were calculated. To reveal the adsorptive characteristics of the produced active carbon, BET surface area measurements were made. Structural analysis was performed using SEM-EDS. The resulting activated carbons with 20% ZnCl(2) solution was the best sample of the produced activated carbons from olive stone with the specific surface area of 790.25 m(2)g(-1). The results show that the produced activated carbon from olive stone is an alternative low-cost adsorbent for removing Cd(II). PMID- 17350830 TI - Synthesis of beta-cyclodextrin and starch based polymers for sorption of azo dyes from aqueous solutions. AB - Three beta-cyclodextrin (polymers 1-3) and a starch-based (polymer 4) polymers were synthesized using hexamethylene diisocyanate (HMDI) as a cross-linking agent in dry dimethylformamide and used as a sorbent for the removal of some selected azo dyes from aqueous solutions. The cross-linked polymers were characterized by Fourier transform infrared spectroscopy, thermogravimetric and differential scanning calorimetric analysis. Results of sorption showed that cyclodextrin and starch based polymers can be effectively used as a sorbent for the removal of anionic azo dyes. The Influence of the amide groups and the chemical structure of azo dyes are also studied. Results of sorption experiments showed that these adsorbent exhibited high sorption capacities toward Direct Violent 51 (80% for polymer 1, 69% for polymer 2, 70% for polymer 3 and 78% for polymer 4). The sorption capacity of dyes on the polymers was dependent on the presence of sulfonate groups of the anionic dyes. In order to explain the results an adsorption mechanism mainly physical adsorption and interactions such as hydrogen bonding, ion-exchange due to the nature of the polymer network and the formation of an inclusion complex due to the beta-CD molecules through host-guest interaction is proposed. PMID- 17350831 TI - Influence of disinfectants on domestic wastewater treatment plant performance. AB - The inhibition effect of the disinfectants was investigated under laboratory conditions. COD removal, nitrification process and oxygen uptake rate were the observed processes. Disinfectants can be divided into a few groups depending on the present biocides. The results of the experiments showed a significant influence of the disinfectants containing sodium hypochlorite on the activated sludge. Domestos and Savo caused the highest inhibition on the respiration, 99% and 100%, respectively; while Asanox and Clorox had the highest effect on COD removal, 97% and 100%, respectively. Bref duo active, which also contains sodium hypochlorite, caused the lowest inhibition for all observed processes. Disinfectants based on other biocides did not cause significant inhibitions. PMID- 17350832 TI - Plantain fibre bundles isolated from Colombian agro-industrial residues. AB - Comestible fruit production from Musaceas plants is an important economical activity in developing countries like Colombia. However, it generates a large amount of agro-industrial residues. Some of them are a potential resource of natural fibres, which can be used as reinforcement for composite materials. In this work, a series of commercial plantain (Musa AAB, cv "Dominico Harton") fibre bundles extracted from pseudostem, leaf sheath and rachis agricultural wastes were analyzed. Mechanical decortication and biological retting processes were used during fiber extraction. No significant differences in composition of vascular bundles were observed for both extraction processes. Gross morphological characteristics and mechanical behavior have been evaluated. Conducting tissues with spiral-like arrangement are observed attached to fibre bundles. This fact suggests a big amount of these tissues in commercial plantain plants. Both used extraction methods are not enough to remove them. Pseudostem fibre bundles have higher specific strength and modulus and lower strain at break than leaf sheath and rachis fibre bundles, having values comparable to other lignocellulosic fibres bundles. PMID- 17350833 TI - Application of the Suzuki-Miyaura cross-coupling to increase antimicrobial potency generates promising novel antibacterials. AB - Antimicrobial peptides have been recognized as a novel class of antibiotics, and several candidates are currently in clinical trials. In this work, a tripeptide derivative containing 4-iodo phenylalanine has been derivatized through the Suzuki-Miyaura cross-coupling. This has enabled the rapid and efficient synthesis of an array of tripeptide derivatives encompassing novel biaryl moieties. The peptide derivatives show high activity against Gram-positive bacteria. PMID- 17350834 TI - Antitumor agents. 256. Conjugation of paclitaxel with other antitumor agents: evaluation of novel conjugates as cytotoxic agents. AB - Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, including camptothecin (CPT), epipodophyllotoxin (EP), colchicine (COL), and glycyrrhetinic acid (GA), at the 2'- or 7-position on paclitaxel (TXL, 1) through an ester, imine, amine, or amide bond. Newly synthesized conjugates were evaluated for cytotoxic activity against replication of several human tumor cell lines. Among them, TXL-CPT conjugates, 8-10, were more potent than TXL itself against the human prostate carcinoma cell line PC-3 (ED(50)=14.8, 3.1, 19.4nM compared with 55.5nM), and conjugate 10 was also 8-fold more active than TXL against the LN-CAP prostate cancer cell line. These compounds also possessed anti-angiogenesis ability as well as lower inhibitory effects against a normal cell line (MRC-5). Thus, conjugates 8-10 are possible antitumor drug candidates, particularly for prostate cancer. PMID- 17350835 TI - Further studies of tyrosine surrogates in opioid receptor peptide ligands. AB - A series of opioid peptide ligands containing modified N-terminal tyrosine (Tyr) residues was prepared and evaluated against cloned human mu, delta, and kappa opioid receptors. This work extends the recent discovery that (S)-4 carboxamidophenylalanine (Cpa) is an effective tyrosine bioisostere. Amino acids containing negatively charged functional groups in place of tyrosine's phenolic hydroxyl lacked receptor affinity, while exchange of Tyr for (S)-4 aminophenylalanine was modestly successful. Peptides containing the new amino acids, (S)-4-carboxamido-2,6-dimethylphenylalanine (Cdp) and (S)-beta-(2 aminobenzo[d]thiazol-6-yl)alanine (Aba), displayed binding (K(i)) and functional (EC(50)) profiles comparable to the parent ligands at the three receptors. Cdp represents the best performing Tyr surrogate in terms of overall activity, while Cpa and Aba show a subtle proclivity toward the delta receptor. PMID- 17350836 TI - Synthesis of fluorescent-labeled aeruginosin derivatives for high-throughput fluorescence correlation spectroscopy assays. AB - The design and solid-phase synthesis of effective fluorescent-labeled aeruginosin derivatives and their application to the fluorescence correlation spectroscopy (FCS)-based competitive binding assay of an aeruginosin library are described. The phenolic hydroxyl group on the (R)-3-(4-hydroxyphenyl)lactic acid (d-Hpla) residue was observed to be suitable for connecting Rhodamine green derivative with minimum loss of biological activity. In addition, the FCS-based binding assay of the library using fluorescent-labeled chemical probes was also achieved. PMID- 17350837 TI - Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors. AB - A novel class of selective Tie-2 inhibitors was derived from a multi-kinase inhibitor 1. By reversing the amide connectivity and incorporating aminotriazine or aminopyridine hinge-binding moieties, excellent Tie-2 potency and KDR selectivity could be achieved with 3-substituted terminal aryl rings. X-ray co crystal structure analysis aided inhibitor design. This series was evaluated on the basis of potency, selectivity, and rat pharmacokinetic parameters. PMID- 17350838 TI - Immuno-stimulating properties of diosgenyl saponins isolated from Paris polyphylla. AB - The effects of three diosgenyl saponins isolated from Paris polyphylla on the immuno-stimulating activity in relation to phagocytosis, respiratory burst, and nitric oxide production in mouse macrophage cells RAW 264.7 have been investigated. Our results showed that all three diosgenyl saponins significantly enhanced phagocytic activity that increased with the concentration of saponins to reach a maximum, and then tended to decrease with higher concentrations. Saponins with sugar moiety directly induced respiratory burst response in RAW 264.7 cells that increased with the concentrations and reached a maximum, then decreased with higher concentrations after 2-h incubations, however, diosgenin had no PMA triggered respiratory burst response. Treatment of RAW 264.7 cells with saponins with sugar moiety for 24-h caused a significant increase in the production of nitric oxide, while diosgenin had no effect at all. Consequently, relationship between molecular structures of three diosgenyl saponins and their immunomodulatory activities was discussed, and a possible mechanism of immuno stimulating function of diosgenyl saponins was accordingly explored. PMID- 17350839 TI - Synthesis and structure-activity relationships of spirohydantoin-derived small molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). AB - The design, synthesis, and SAR of a series of substituted spirohydantoins are described. Optimization of an in-house screening hit gave compounds that exhibited potent binding affinity and functional activity at MCH-R1. PMID- 17350840 TI - Aryl sulfonamido indane inhibitors of the Kv1.5 ion channel. AB - A collection of aryl sulfonamido indanes based on the lead compound 1 was synthesized and evaluated for Kv1.5 inhibitory activity. Kv1.5 inhibitors have the potential to be atrium-selective agents for treatment of atrial fibrillation. (1R,2R)-1 has an IC(50) of 0.033microM against Kv1.5 and is selective against other cardiac ion channels, including hERG. PMID- 17350841 TI - 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV. AB - A novel series of 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives were designed and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4). The phenylalanine series afforded compounds such as 10 that were potent and selective (DPP-4, IC(50)=28nM), but exhibited limited oral bioavailability. The corresponding cyclohexylalanine derivatives such as 25 afforded improved PK exposure and efficacy in a murine OGTT experiment. The X-ray crystal structure of 25 bound to the DPP-4 active site is presented. PMID- 17350842 TI - Ironing out the wrinkles of neutrophil phagocytosis. AB - Though phagocytosis of microbes by professional phagocytes such as neutrophils is crucial for the survival of the host, it is still unclear how the apparent 'stretching' of the plasma membrane is achieved. Microscopically, pseudopod extension, particulate engulfment and phagosome closure all require seemingly large expansions of the cell surface area. Although actual membrane stretching can be ruled out on the basis of physical properties of lipid bilayers, the addition of new membrane from within the cell, either by exocytosis or phagosomal fusion with endoplasmic reticulum membrane, might provide an explanation. However, these events do not seem to have major roles during phagocytosis by neutrophils. Instead, neutrophils might use a more primitive mechanism, that is, the unfolding of surface membrane wrinkles, to provide the additional membrane for phagocytosis. Here, we briefly discuss why membrane unwrinkling provides a feasible hypothesis for membrane expansion during neutrophil phagocytosis, and suggest a potential molecular mechanism for neutrophil control over membrane surface wrinkles, and the potential signalling route. PMID- 17350844 TI - Intraventricular meningiomas: a surgical challenge. AB - BACKGROUND: Primary intraventricular meningiomas (IVM) pose a surgical challenge as they often remain asymptomatic until they become very large; have close proximity to vital intraventricular structures; and, their vascular supply is often encountered only after significant tumor debulking. In this study, the surgical management of IVM is discussed. METHODS: Between 1989 and 2003, nine patients (7 with lateral and 2 with fourth ventricular) IVM, were operated upon. Raised intracranial pressure, gait ataxia, memory impairment, seizures (motor and sensory) were the main presentations. Four had hydrocephalus while five had either a sequestered temporal or occipital horn. All were large tumors with an average size more than 5.3 cm. The lateral ventricular IVM were accessed by the posterior middle temporal gyrus (n=5) or the superior parietal lobule (n=2) approach. A midline suboccipital craniectomy was used for the fourth ventricular IVM. RESULTS: Total excision was achieved in eight and partial excision in one. Patients with lateral ventricular tumors required a postoperative intraventricular drain for a minimum period of 48 hours. The main morbidity included visual field defects and transient hemiparesis, seizure and meningitis. The one patient with partial excision died 6 weeks later due to transtentorial herniation as a result of intratumoral bleed and lateral ventricular sequestration. CONCLUSIONS: An IVM, being initially asymptomatic, usually attains a large size before detection. During surgery, its devascularisation is usually achieved only after significant tumor debulking. Development of hydrocephalus or ventricular sequestration should be constantly monitored and may be avoided in the postoperative period by continuous external ventricular drainage. PMID- 17350845 TI - First synthesis of 7alpha- and 7beta-amino-DHEA, dehydroepiandrosterone (DHEA) analogues and preliminary evaluation of their cytotoxicity on Leydig cells and TM4 Sertoli cells. AB - Efficient syntheses of new DHEA analogues, and their apoptotic and necrotic effects on Leydig cells and TM4 Sertoli cells are described. The key step in the synthetic strategy of 7-amino-DHEA derivatives involves a bromination on C-7 position to give an epimeric mixture of bromides which were substituted by azides and reduced to give 7alpha- and 7beta-amino-3beta-hydroxyandrost-5-en-17-ones. No cytotoxic effect induced by apoptosis mechanism was observed on Leydig and TM4 Sertoli cells by treatment with these amino-DHEA analogues. A necrotic effect was induced only in TM4 Sertoli cells. The best activity was obtained with 7alpha,beta-amino-androst-5-en-3beta-ol and 7beta-amino-3beta-hydroxy-androst-5 en-17-one. PMID- 17350846 TI - Anticancer, neuroprotective activities and computational studies of 2-amino-1,3,4 thiadiazole based compound. AB - Anticancer activity studies of 2-(4-fluorophenylamino)-5-(2,4-dihydroxyphenyl) 1,3,4-thiadiazole (FABT), as one of the most promising derivatives from the N substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole set, have been continued. The tested compound inhibited proliferation of tumor cells derived from cancers of nervous system (medulloblastoma/rhabdosarcoma, neuroblastoma, and glioma) and peripheral cancers including colon adenocarcinoma and lung carcinoma. The anticancer effect of FABT was attributed to decreased cell division and inhibited cell migration. Furthermore, in anticancer concentrations it exerted a trophic effect in neuronal cell culture and had no influence on viability of normal cells including astrocytes, hepatocytes, and skin fibroblasts. Moreover, a prominent neuroprotective activity of FABT was observed in the neuronal cultures exposed to neurotoxic agents like serum deprivation and glutamate. To determine probability of tautomeric transition and indicate potential sites of interactions of FABT molecule with the receptor, quantum-chemical calculations with the ab initio Hartree-Fock model were made. PMID- 17350847 TI - Studies of inclusion complexes of natural and modified cyclodextrin with (+)catechin by NMR and molecular modeling. AB - The aim of this paper is to describe the inclusion properties and the factors affecting the complexation selectivity and stabilization of catechin (CA) into beta-cyclodextrin (beta-CD) and two of its derivatives, namely Heptakis 2,6-di-O methyl-beta-cyclodextrin (DM-beta-CD) and 2 hydroxypropyl-beta-cyclodextrin (HP beta-CD). Analysis of the proton shift change using the continuous variation method confirm the formation of a 1:1 stoichiometric complex for catechin and the different CDs in aqueous medium. The formations constant obtained by diffusion ordered spectroscopy (DOSY) techniques indicated the following trend upon complex formation: beta-CD>HP-beta-CD>DM-beta-CD. The detailed spatial configuration is proposed based on 2D NMR methods. These results are further interpreted using molecular modeling studies. The latter results are in good agreement with the experimental data. The models confirm that when CA-beta-CD is formed, the catechol moiety in the complex is oriented toward the primary rim; however when CD is derivatized to HP-beta-CD and DM-beta-CD this ring is oriented toward the secondary rim. PMID- 17350848 TI - U/Th dating of carbonate deposits from Constantina (Sevilla), Spain. AB - Uranium-series method has been applied to continental carbonate deposits from Constantina, Seville, in Spain. All samples analysed were impure carbonates and the leachate-leachate method was used to obtain activity ratios in carbonate fraction. Leachate-residue methods were applied to one of the samples in order to compare with leachate-leachate method, but leachate-residue method assumptions did not meet and ages resulting from leachate-residue methods were not valid. Ages obtained by leachate-leachate method range from 1.8 to 23.5ky BP and are consistent with stratigraphical positions of samples analysed. Initial activity ratios for uranium isotopes are practically constant in this period, thus indicating that no changes in environmental conditions occur between 1.8 and 23.5ky period. PMID- 17350849 TI - Retransfusion of pericardial blood does not trigger systemic coagulation during cardiopulmonary bypass. AB - OBJECTIVE: During cardiopulmonary bypass (CPB), systemic coagulation is believed to become activated by blood contact with the extracorporeal circuit and by retransfusion of pericardial blood. To which extent retransfusion activates systemic coagulation, however, is unknown. We investigated to which extent retransfusion of pericardial blood triggers systemic coagulation during CPB. METHODS: Thirteen patients undergoing elective coronary artery bypass grafting surgery were included. Pericardial blood was retransfused into nine patients and retained in four patients. Systemic samples were collected before, during and after CPB, and pericardial samples before retransfusion. Levels of prothrombin fragment F(1+2) (ELISA), microparticles (flow cytometry) and non-cell bound (soluble) tissue factor (sTF; ELISA) were determined. RESULTS: Compared to systemic blood, pericardial blood contained elevated levels of F(1+2), microparticles and sTF. During CPB, systemic levels of F(1+2) increased from 0.28 (0.25-0.37; median, interquartile range) to 1.10 (0.49-1.55) nmol/l (p=0.001). This observed increase was similar to the estimated (calculated) increase (p=0.424), and differed significantly between retransfused and non-retransfused patients (1.12 nmol/l vs 0.02 nmol/l, p=0.001). Also, the observed systemic increases of platelet- and erythrocyte-derived microparticles and sTF were in line with predicted increases (p=0.868, p=0.778 and p=0.205, respectively). Before neutralization of heparin, microparticles and other coagulant phospholipids decreased from 464 microg/ml (287-701) to 163 microg/ml (121-389) in retransfused patients (p=0.001), indicating rapid clearance after retransfusion. CONCLUSION: Retransfusion of pericardial blood does not activate systemic coagulation under heparinization. The observed increases in systemic levels of F(1+2), microparticles and sTF during CPB are explained by dilution of retransfused pericardial blood. PMID- 17350850 TI - A complete traumatic tracheal rupture. PMID- 17350851 TI - Analysis of the fiber architecture of the heart by quantitative polarized light microscopy. Accuracy, limitations and contribution to the study of the fiber architecture of the ventricles during fetal and neonatal life. AB - OBJECTIVE: To address the advantages and drawbacks of quantitative polarized light microscopy for the study of myocardial cell orientation and to identify its contribution in the field. METHODS: Quantitative polarized light microscopy allows to measure the orientation of myocardial fibers into the ventricular mass. For each pixel of a horizontal section, this orientation is the mean value of the directions of all myosin filaments contained in the thickness of the section for each pixel of the section and is accounted for by two angles, the azimuth angle, which is the angle of the fiber in the plane of the section, and the elevation angle, which measures the way the fiber escapes from the section. The azimuth is accurately measured, and its range of definition is complete from 0 degrees to 180 degrees . The elevation angle can be defined only in the range 0 degrees to 90 degrees . It is accurately measured between 20 degrees and 70 degrees . From 0 degrees to 20 degrees , there is a systematic bias raising the measured values, and from 70 degrees to 90 degrees , the angle is not accurately measured. RESULTS: With this method, we validated Streeter's conjecture concerning the architecture of the left ventricle. We formulated a pretzel conjecture about the fiber architecture of the whole ventricular mass during fetal period. In our model, elaborated by visual analysis of registered maps of orientation, the fibers run like geodesics on a nested set of 'pretzels'. Next, the validity of the helical ventricular myocardial band model of Torrent-Guasp has been examined. It appears that the band model does not account for the patterns observed in our data during the fetal period. However, after the major events of postnatal cardiovascular adaptation, our data can neither discard nor confirm Torrent Guasp's model. CONCLUSIONS: Present limitations of quantitative polarized light analysis can neither confirm nor discard the existing models of fiber orientation in the whole ventricular mass after the neonatal period. However, the problems of mathematical and experimental validation of these two models have been posed in a rigorous manner. Non-ambiguous fiber tracking and demonstration of these models will require significant improvement of the definition range of the elevation angle that should be extended to 180 degrees . PMID- 17350852 TI - Left atrial invasion by pulmonary adenocarcinoma. PMID- 17350853 TI - Replacing the diseased aortic valve and the proximal aorta in the elderly patient. AB - Subcoronary implantation of the Medtronic stentless bioprosthesis and an extension using a vascular tube prosthesis provide a safer alternative to the more invasive conventional composite graft replacement or a full root replacement using a homograft or a stentless valve. The advantage lies in eliminating the need for coronary mobilisation and anastomosis which actually lead to the increased risk in those procedures. PMID- 17350854 TI - Right extrapleural pneumonectomy for malignant mesothelioma via median sternotomy or thoracotomy? Short- and long-term results. AB - OBJECTIVE: To examine the short- and long-term results of right extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MM) via median sternotomy or thoracotomy. METHODS: We analysed the results of EPP in consecutive patients with early stage MM undergoing a radical surgery protocol for MM over a 7-year period. Initially thoracotomy, but later median sternotomy, was the incision of choice for right-sided tumours. The effects of the change of approach on perioperative course and survival were analysed. RESULTS: EPP was performed in 105 patients (50 left thoracotomy, 22 right thoracotomy, 28 sternotomy, 5 combined sternotomy and right thoracotomy). Operation time was faster with median sternotomy than right thoracotomy (p=0.008). Right thoracotomy was associated with higher epidural infusion volume in the first 3 days than median sternotomy (p<0.001). There were fewer postoperative complications in the sternotomy group (p=0.05). There were no differences in pathological stage, completeness of resection or duration of postoperative stay. Median survival following left thoracotomy, right thoracotomy and median sternotomy was 18.3, 8.5 and 17.7 months, respectively (p=0.02). Planned neoadjuvant or adjuvant chemotherapy was more common following median sternotomy than right thoracotomy (p=0.01). However, compared with the left thoracotomy and sternotomy groups, right EPP performed via thoracotomy was an independent predictor of poor prognosis (hazard ratio 2.3 (95% confidence intervals, CI 1.3-4.1), p=0.02). No wound complications or tumour recurrence have been observed following median sternotomy. CONCLUSIONS: Median sternotomy should be considered as an alternative approach to thoracotomy for right EPP. PMID- 17350855 TI - Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment. AB - OBJECTIVE: Local recurrence remains a major problem in the treatment of malignant pleural mesothelioma. The aim of the underlying study was to establish a standardised local recurrence model in rats which enables to study different intrapleural therapies. MATERIALS AND METHODS: Fifty microlitre containing 1 x 10(6) cells of a syngeneic rat malignant mesothelioma cell line (II-45), established from mesothelioma in Fischer 344 rats exposed to asbestos, were inoculated subpleurally via a left-sided thoracotomy. Tumour size was assessed 6 days later and the tumour nodule completely resected. Evaluation of recurrence at the resection site was performed after 10 days (n=6) and 6 days (n=6). The recurrent nodule was histopathologically confirmed. In a second experiment, this new recurrence model was evaluated for the effect of intrapleural therapy with different agents: 4 ml of cisplatin-solution (100mg(2)/kg BW), cisplatin combined with the fibrin-based sealant Vivostat, 4 ml taurolidine 2%, repeated injection of 1 microg of the chemokine CCL-19 at the tumour site and 4 ml povidone-iodine in a dilution 1:10. In a control group, the chest cavity was filled with 4 ml 0.9% NaCl. The primary endpoint was the extent of tumour recurrence. RESULTS: Six days after inoculation, all animals presented a standardised tumour nodule at the injection site of a mean diameter of 5.1 (+/-0.8)mm. Evaluation of the recurrence after 10 days showed a relapse directly at the resection site, but additional tumour nodules on the ipsi- and contralateral chest wall were found and histologically confirmed. The animals that were sacrificed 6 days after resection of the tumour nodule showed a recurrence only at the resection site with no macroscopic or microscopic evidence of other tumour. Resection of the tumour nodule combined with intrapleural application of the different agents lead to clear reduction of recurrence. The strongest effect was observed after intrapleural application of cisplatin-Vivostat with significant decrease of the longest, widest and thickest diameter of the recurrence. CONCLUSIONS: With this new recurrence model for investigation of malignant pleural mesothelioma in rats, we were able to investigate new intrapleural therapies after pneumonectomy. The intrapleural application of cisplatin-Vivostat significantly reduced the extent of local recurrence. PMID- 17350856 TI - Effect of preoperative angiotensin converting enzyme inhibitor or angiotensin receptor blocker use on the frequency of atrial fibrillation after cardiac surgery: a cohort study from the atrial fibrillation suppression trials II and III. AB - BACKGROUND: Two recent meta-analyses demonstrated that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce the risk of developing new-onset atrial fibrillation (AF) by nearly 50%. However, the ability of ACEIs or ARBs to prevent postoperative atrial fibrillation (POAF) after cardiac surgery has not been adequately evaluated. OBJECTIVE: To evaluate the impact of preoperative ACEI or ARB use on the incidence of POAF after cardiac surgery. METHODS: Patients undergoing coronary artery bypass grafting and/or valvular surgery from the (atrial fibrillation suppression trials II and III (AFIST II and III) randomized, controlled trials were evaluated in this cohort evaluation. Data in respect to patient demographics, surgical characteristics, medication utilization and the incidence of POAF (defined as AF lasting at least 5 min in duration documented by telemetry) were all uniformly and prospectively collected as part of AFIST II and III. Multivariate logistic regression was utilized to calculate adjusted odds ratios with 95% confidence intervals. RESULTS: A total of 338 patients were evaluated of which 175 (51.8%) received an ACEI or ARB preoperatively and 163 (48.2%) did not. The study population was 65.7+/-9.1 years of age, 77.8% were male, 11.2% underwent valve surgery, 3.6% had prior AF, 10.1% had heart failure and 84.0 and 37.9% received postoperative beta blockade and prophylactic amiodarone, respectively. In total, 110 (32.5%) patients developed POAF. Upon multivariate logistic regression, the preoperative use of an ACEI or ARB was not found to be associated with a statistically significant reduction in POAF (adjusted odds ratio; 0.71, 95% CIs 0.42-1.20). CONCLUSIONS: Although preoperative ACEI or ARB use reduced the odds of developing POAF by 29%, this association with not found to be statistically significant. A study with approximately 600 subjects would be needed to discern if ACEIs or ARBs truly impact POAF. PMID- 17350857 TI - Allografts for aortic valve or root replacement: insights from an 18-year single center prospective follow-up study. AB - OBJECTIVE: Whether allografts are the biological valve of choice for AVR in non elderly patients remains a topic of debate. In this light we analyzed our ongoing prospective allograft AVR cohort and compared allograft durability with other biological aortic valve substitutes. METHODS: Between April 1987 and October 2005, 336 patients underwent 346 allograft AVRs (95 subcoronary, 251 root replacement). Patient and perioperative characteristics, cumulative survival, freedom from reoperation, and valve-related events were analyzed. Using microsimulation, for adult patients, age-matched actual freedom from allograft reoperation was compared to porcine and pericardial bioprostheses. RESULTS: Mean age was 45 years (range 1 month to 83 years); 72% were males. Etiology was mainly endocarditis 32% (active 22%), congenital 31%, degenerative 9%, and aneurysm/dissection 12%. Twenty-seven percent underwent prior cardiac surgery. Hospital mortality was 5.5% (N=19). During follow-up (mean 7.4 years, maximum 18.5 years, 98% complete), 54 patients died; there were 57 valve-related reoperations (3 early technical, 11 non-structural, 39 structural valve deterioration (SVD), 4 endocarditis), 5 cerebrovascular accidents, 1 fatal bleeding, 8 endocarditis. Twelve-year cumulative survival was 71% (SE 3), freedom from reoperation for SVD 77% (SE 4); younger patient age was associated with increased SVD rates. Actual risk of allograft reoperation was comparable to porcine and pericardial bioprostheses in a simulated age-matched population. CONCLUSIONS: The use of allografts for AVR is associated with low occurrence rates of most valve-related events, but over time the risk of SVD increases, comparable to stented xenografts. It remains in our institute the preferred valve substitute only for patients with active aortic root endocarditis and for patients in whom anticoagulation should be avoided. PMID- 17350859 TI - Cloning and characterization of three hypothetical secretion chaperone proteins from Xanthomonas axonopodis pv. citri. AB - Xanthomonas axonopodis pv. citri (Xac) causes citrus canker in plantations around the world and is of particular significance in Brazil where its incidence has risen exponentially over the past decade. Approximately one third of the predicted Xac open reading frames show no homology, or homology with very low score with that of known sequences. It is believed that Xac utilizes secretion systems to transfer virulence proteins into susceptible eukaryotic cells. This process is assisted by secretion chaperones that maintain virulence proteins partly or completely unfolded during translocation. We have cloned three of these hypothetical secretion chaperones: XAC0419 and XAC1346 from type III secretion system (TTSS) and XACb0033 from type IV secretion system (TFSS). All proteins were cloned in a pET23a vector (Novagen), expressed at 37 degrees C using a BL21(DE3)pLysS Escherichia coli strain and purified by ion exchange and gel filtration chromatographic methods. Pure proteins were characterized using spectroscopic measurements: circular dichroism, and both static and lifetime emission fluorescence in the case of XACb0033. The analyzed proteins are stable at elevated temperatures (up to 65 degrees C) and exhibit alpha-helix content from approximately 30% (XACb003) to approximately 87% (XAC1346). XACb0033 exhibits lifetimes in the fluorescence experiments that indicate different neighborhoods for its tryptophan residues. These chaperones have the characteristics of TTSS and TFSS: all are small, with a high alpha-helix content, and without ATP-binding or ATP-hydrolyzing activity. PMID- 17350858 TI - Rosuvastatin displays anti-atherothrombotic and anti-inflammatory properties in apoE-deficient mice. AB - Inflammation contributes importantly to all stages of atherosclerosis, including the onset of acute thrombotic complications. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. Moreover, statins have been shown to possess several pleiotropic properties independent of cholesterol lowering in experimental settings. Based on these premises, we investigated the anti-inflammatory and anti-atherothrombotic properties of rosuvastatin in vivo, testing its effect on cholesterol and monocyte accumulation, and on adhesion molecules and tissue factor (TF) expression. ApoE-deficient female mice were fed a cholesterol-rich diet containing rosuvastatin (0, 1, 2 or 10 mg kg(-1)d(-1)) for 12 weeks. Treatment with rosuvastatin did not significantly affect either body weight gain or plasma total cholesterol (C) and triglyceride levels. However, rosuvastatin treatment dose-dependently reduced ICAM-1 expression in the aortic valves (V) (up to 40% inhibition, p<0.05) and in the proximal segment of the ascending aorta (AA) ( 50%, p<0.001). Similarly, rosuvastatin inhibited VCAM-1 expression in the V ( 40%) and in the AA (-35%, p<0.05). Moreover, there was a reduced accumulation of macrophages in the V in a dose-dependent and statistically significant manner ( 45%, p<0.01). These anti-inflammatory effects were reflected in a reduction of cholesterol deposition in the entire aorta, both in the free and in the esterified form. Finally, the expression of tissue factor, the most potent pro thrombogenic agent, was consistently reduced in AA by rosuvastatin treatment ( 71%, p<0.001). Altogether, these data demonstrate that rosuvastatin has anti inflammatory and anti-atherothrombotic activities in apoE-deficient mice that could translate in a beneficial effect on atherogenesis. PMID- 17350860 TI - Discontinuous membrane helices in transport proteins and their correlation with function. AB - Alpha-helical bundles and beta-barrel proteins represent the two basic types of architecture known for integral membrane proteins. Irregular structural motifs have been revealed with the growing number of structures determined. "Discontinuous" helices are present in membrane proteins that actively transport ions. In the Ca(2+)-ATPase, a primary active transporter, and in the secondary transporters NhaA, LeuT(Aa), ClC H(+)/Cl(-) exchanger and Glt(Ph), the helical structure of two membrane segments is interrupted and the interjacent polypeptide chain forms an extended peptide. The discontinuous helices are integrated in the membrane either as transmembrane-spanning or hairpin-type segments. In addition, the secondary transporters have inverted internal duplication domains, which are only weakly correlated with their amino acid sequence. The symmetry comprises either parts of or the complete molecule, but always includes the discontinuous helices. The helix-peptide-helix motif is correlated with the ion translocation function. The extended peptides with their backbone atoms, the helix termini and the polar/charged amino acid residues in close vicinity provide the basis for ion recognition, binding and translocation. PMID- 17350861 TI - Identification and characterization of two homologues of interferon-stimulated gene ISG15 in crucian carp. AB - ISG15 is one of the most strongly induced genes upon viral infection, interferon (IFN) stimulation, and lipopolysaccharide (LPS) stimulation, and only one copy has been found in mammals so far. Here two fish ISG15 genes, termed CaISG15-1 and CaISG15-2, have been cloned and sequenced from UV-inactivated GCHV (grass carp haemorrhagic virus)-infected and IFN-produced CAB cells (crucian carp Carassius auratus blastulae embryonic cells) by suppression subtractive hybridization. The full-length cDNA sequences of two crucian carp ISG15 encode a 155-amino-acid protein and a 161-amino-acid protein, both of which show 78.9% identity overall and possess the characteristic structures of mammalian ISG15 proteins including two tandem ubiquitin-like domains and the C-terminal canonical LRLRGG motif. In CAB cells treated with different stimuli including active virus, UV-inactivated GCHV and IFN containing supernatant (ICS), the expression of both CaISG15-1 and CaISG15-2 was upregulated but displayed different kinetics. Poly I:C and LPS were also able to induce an increase in mRNA for both genes. In CAB cells responsive to active GCHV, UV-inactivated GCHV, CAB ICS, Poly I:C and LPS, CaISG15-1 was upregulated more significantly than CaISG15-2. These results suggest that there are two ISG15 homologues in crucian carp, both of which might play distinct roles in innate immunity against viral and bacterial infection. PMID- 17350862 TI - Effect of spatial attention on stimulus-specific haemodynamic repetition effects. AB - The aim of this fMRI study was to investigate whether spatial attention to the initial and/or repeated presentation of a stimulus is necessary to observe repetition-related modulations of the neural responses evoked by that stimulus. During each trial, two stimuli were presented simultaneously, one left and one right of fixation. During each block, participants were instructed to attend covertly to stimuli in one of the two hemifields and respond whether each was a face or house, ignoring the contralateral stimulus. Regions that preferred one stimulus category over the other, such as the fusiform face area and parahippocampal place area, showed evidence of some processing of the ignored stimuli. However, a reduced response to repeated stimuli (repetition suppression) was only reliable for preferred stimuli when both their initial and repeated presentations were attended. This suggests that attention is necessary for both the acquisition and expression of the neural mechanisms that underlie repetition suppression, at least over the lags of 2-16 intervening trials used here. PMID- 17350863 TI - Thiazolidinediones exhibit different effects on preadipocytes isolated from rat mesenteric fat tissue and cell line 3T3-L1 cells derived from mice. AB - The effects of PPAR-gamma agonists, thiazolidinediones (TZDs), on preadipocytes isolated from rat mesenteric adipose tissue and murine cell line 3T3-L1 were compared using an in vitro cell culture system. After each cell formed a confluent monolayer under appropriate medial conditions, pioglitazone or troglitazone was applied at 10 microM to each medium for cell maturation. We observed morphological changes in each cell, especially the accumulation of lipid droplets in the cytoplasm, during the culture periods. At the end of culture, DNA content, triglyceride (TG) content and glycerol-3-phosphate dehydrogenase (GPDH) activity were determined. Adiponectin concentrations in each culture medium were also measured during appropriate experimental periods. Application of TZDs increased the DNA content, TG accumulation and GPDH activity in the 3T3-L1 cells but not in the mesenteric adipocytes. Although TG accumulation was unchanged, the number of lipid particles was decreased and the size of lipid particles in the mesenteric adipocytes was increased by TZD application. Although the TZDs increased adiponectin release from the 3T3-L1 cells, adiponectin release from mesenteric adipocytes was suppressed (P<0.05). Thus, the effects of TZDs differed between the primary culture of mesenteric adipose cells and the line cell culture of 3T3-L1 cells. The source of adipocytes is an important factor in determining the action of TZDs in vitro, and particular attention should be paid when evaluating the effect of PPAR-gamma agonists on adipose tissues. PMID- 17350864 TI - The proline permease of Aspergillus nidulans: functional replacement of the native cysteine residues and properties of a cysteine-less transporter. AB - The major proline transporter (PrnB) of Aspergillus nidulans belongs to the Amino acid Polyamine Organocation (APC) transporter superfamily. Members of this family have not been subjected to systematic structure-function relationship studies. In this report, we examine the functional replacement of the three native Cys residues (Cys54, Cys352 and Cys530) of PrnB and the properties of an engineered Cys-less PrnB protein, as background for employing a Cys-scanning mutagenesis approach. We show that simultaneous replacement of Cys54 with Ala, Cys352 with Ala and Cys530 with Ser results in a functional Cys-less PrnB transporter. We also introduce the use of a biotin-acceptor domain tag to quantitate protein levels of the engineered PrnB mutants by Western blot analysis. Finally, by using the background of the Cys-less PrnB transporter, we evaluate the functional importance of amino acids Q219, K245 and F248 of PrnB, which our previous data had suggested to be involved in the mechanism of PrnB-mediated proline uptake. In the current study, we show that K245 and F248 but not Q219 are critical for PrnB mediated proline uptake. PMID- 17350865 TI - A new strategy for fast radiofrequency CW EPR imaging: direct detection with rapid scan and rotating gradients. AB - Rapid field scan on the order of T/s using high frequency sinusoidal or triangular sweep fields superimposed on the main Zeeman field, was used for direct detection of signals without low-frequency field modulation. Simultaneous application of space-encoding rotating field gradients have been employed to perform fast CW EPR imaging using direct detection that could, in principle, approach the speed of pulsed FT EPR imaging. The method takes advantage of the well-known rapid-scan strategy in CW NMR and EPR that allows arbitrarily fast field sweep and the simultaneous application of spinning gradients that allows fast spatial encoding. This leads to fast functional EPR imaging and, depending on the spin concentration, spectrometer sensitivity and detection band width, can provide improved temporal resolution that is important to interrogate dynamics of spin perfusion, pharmacokinetics, spectral spatial imaging, dynamic oxymetry, etc. PMID- 17350866 TI - Nonuniform sampling and maximum entropy reconstruction applied to the accurate measurement of residual dipolar couplings. AB - Residual dipolar couplings (RDC) provide important global restraints for accurate structure determination by NMR. We show that nonuniform sampling in combination with maximum entropy reconstruction (MaxEnt) is a promising strategy for accelerating and potentially enhancing the acquisition of RDC spectra. Using MaxEnt-processed spectra of nonuniformly sampled data sets that are reduced up to one fifth relative to uniform sampling, accurate 13C'-13Calpha RDCs can be obtained that agree with an RMS of 0.67 Hz with those derived from uniformly sampled, Fourier transformed spectra. While confirming that frequency errors in MaxEnt spectra are very slight, an unexpected class of systematic errors was found to occur in the 6th significant figure of 13C' chemical shifts of doublets obtained by MaxEnt reconstruction. We show that this error stems from slight line shape perturbations and predict it should be encountered in other nonlinear spectral estimation algorithms. In the case of MaxEnt reconstruction, the error can easily be rendered systematic by straightforward optimization of MaxEnt reconstruction parameters and self-cancels in obtaining RDCs from nonuniformly sampled, MaxEnt reconstructed spectra. PMID- 17350867 TI - Prediction of cytotoxicity data (CC(50)) of anti-HIV 5-phenyl-1-phenylamino-1H imidazole derivatives by artificial neural network trained with Levenberg Marquardt algorithm. AB - A Levenberg-Marquardt algorithm trained feed-forward artificial neural network in quantitative structure-activity relationship (QSAR) was developed for modeling of cytotoxicity data for anti-HIV 5-phenyl-1-phenylamino-1H-imidazole derivatives. A large number of descriptors were calculated with Dragon software and a subset of calculated descriptors was selected with a stepwise regression as a feature selection technique. The 28 molecular descriptors selected by stepwise regression, as the most feasible descriptors, were used as inputs for feed forward neural network. The neural network architecture and its parameters were optimized. The data were randomly divided into 31 training and 11 validation sets. The prediction ability of the model was evaluated using validation data set and "one-leave-out" cross validation method. The root mean square errors (RMSE) and mean absolute errors for the validation data set were 0.042 and 0.024, respectively. The prediction ability of ANN model was also statistically compared with results of linear free energy related model. The obtained results show the validity of proposed model in the prediction of cytotoxicity data of corresponding anti-HIV drugs. PMID- 17350868 TI - Inhaled corticosteroids for recurrent respiratory symptoms in preschool children in general practice: randomized controlled trial. AB - BACKGROUND: Therapy with inhaled corticosteroids (ICS) is beneficial in patients with asthma. However, in preschool children with symptoms like cough, wheeze, or shortness of breath diagnosing asthma is difficult. Therefore, the role of ICS in the management of preschool children with recurrent respiratory symptoms is unclear. We assessed the effectiveness of ICS in preschool children with recurrent respiratory symptoms in general practice. METHODS: In this multicenter, randomized, double blind, placebo controlled trial, 96 children aged 1-5 years consulting their general practitioners for recurrent respiratory symptoms and in whom treatment with ICS was considered by the general practitioner were randomly allocated to receive ICS (fluticasone propionate 200 mcg/day by metered dose inhaler/spacer combination) or placebo for 6 months. Outcome assessments were carried out 1, 3, and 6 months after randomization. The primary outcome measure was the symptom score (cough, shortness of breath and wheeze during day and night) as measured by a symptom diary card. Secondary endpoints were symptom-free days, use of rescue medication, adverse events, and lung function variables as measured by the interrupter technique and forced oscillation technique. RESULTS: During the 6 months treatment period, symptoms improved in both groups, with no differences between ICS and placebo. In addition, none of the secondary outcome parameters showed differences between both treatment groups. CONCLUSION: ICS treatment has no beneficial effect in preschool children with recurrent respiratory symptoms in general practice. We therefore recommend a watchful waiting policy with only symptomatic treatment in these children. General practitioners and pediatricians should be aware of the high probability of overtreatment when prescribing ICS in these children. PMID- 17350869 TI - Development of skin structure and cutaneous water loss in nestling desert house sparrows from Saudi Arabia. AB - The outer layer of the epidermis, the stratum corneum (SC), contains lipids and corneocytes, which together form layers that limit cutaneous water loss (CWL). We examined the development of structure of the SC and CWL in nestling House Sparrows (Passer domesticus) from Saudi Arabia. We measured CWL of nestlings, and characterized development of their epidermis using electron microscopy. We tested two antagonistic hypotheses, that CWL decreases as nestlings age, a response to increased thickness of SC, and an opposite idea that CWL increases as nestlings age even though the number of layers of the SC remains constant. CWL of nestling House Sparrows varied with developmental stages, in a non-linear fashion, but not significantly so. CWL of nestlings averaged 7.31+/-1.5 g H(2)O/(m(2) h), whereas for adults it was 4.95 g/(m(2) h); adult CWL was 67.7% that of nestlings. We found that morphology of the SC did not change linearly with age, but seemed to vary with developmental stage. CWL decreased as the SC thickness increased and as the total thickness of the corneocytes increased. Further, we found that CWL decreased as the thickness of the extracellular space increased, number of corneocytes increased, and proportion of the SC that is extracellular space increased. PMID- 17350870 TI - Purification, characterization, and cDNA cloning of opine dehydrogenases from the polychaete rockworm Marphysa sanguinea. AB - Alanopine dehydrogenase (AlDH) and three isoforms of strombine/alanopine dehydrogenase (St/AlDH) were purified from muscle tissue of the polychaete rockworm Marphysa sanguinea. The four enzymes, which can be distinguished by the isoelectric point, are monomeric 42 kDa proteins, possess similar pH-activity profiles, and display specificity for pyruvate and NAD(H). The three isoforms of St/AlDH show equivalent Km and Vmax for glycine and L-alanine and for D-strombine and meso-alanopine. Free amino acid levels in the muscle and D-strombine accumulation in vivo during muscle activity suggest that St/AlDHs function physiologically as StDH. AlDH shows specificity for L-alanine and meso-alanopine, but not for glycine or D-strombine. The amino acid sequences of AlDH and one of the St/AlDH isoforms were determined by a combination of amino acid sequence analysis and cDNA cloning. St/AlDH cDNA consisted of 1586 bp nucleotides that encode a 399-residue protein (43,346.70 Da), and AlDH cDNA consisted of 1587 bp nucleotides that encode a 399-residue protein (43,886.68 Da). The two amino acid sequences deduced from the cDNA displayed 67% amino acid identity, with greatest similarity to that of tauropine dehydrogenase from the polychaete Arabella iricolor. PMID- 17350871 TI - Integrated physiology and pathophysiology of CB1-mediated effects of the endocannabinoid system. AB - The discovery of the endocannabinoid system (ECS) has raised a large interest in the scientific community providing us with a strikingly long list of apparently independent multi organ effects. As a result, in most reviews on this issue the main function of the ECS is considered as modulatory. Unfortunately, this vision does not add much to our understanding of the specific biological function of the ECS. Thus, modulatory is what in general all biological systems are or should be. In this review we will show that the apparent inconsistent puzzle of the very different tissue specific effects of endocannabinoids (ECs) can be reconstructed in one unitary picture. This picture clearly shows that all the different CB1 mediated effects of ECs sub-serve one major physiological function: to facilitate and increase energy storage. We will also analyze the implications of this unitary vision of the ECS in different contexts. First, in the context of the systems that regulate energy balance, introducing a new systematization based on two homeostatic systems: an endostatic and an exostatic system. Second, in the context of evolution, showing how the function of the ECS has shifted from essential to survival to almost pathological in current times. Finally, in a pathophysiological context, introducing the new concept of "proactive evolution diseases", which can explain the current obesity epidemic and the role the ECS plays in it. PMID- 17350872 TI - Late onset neurogenic claudication in a case of metallic intradural ballistic fragment. AB - Metallic foreign bodies in the intradural location are rare. Even rarer is the absence of neurodeficit in such cases. We report a case where the patient came to the outdoor department of our hospital with symptoms of neurogenic claudication. From history the patient did not volunteer the information which was pertinent to his symptomatology. On examination he was asked about the small scar in his lumbar region. He attributed it to the subjectively insignificant trauma he had sustained when he had been trapped in a crossfire and had been hit by a fragment. The patient had been absolutely symptom free for 12 months after the event followed by 6 months of increasing claudication. X-ray and CT examination revealed the presence of a metallic foreign body in the lumbar spinal canal. Surgical exploration and removal correlated the presence. This case report substantiates the view that a patient with a foreign body in the spinal canal is always a potential candidate for surgery. PMID- 17350873 TI - [Malignant ovarian germ cell tumours: a trial of 36 cases]. AB - OBJECTIVE: With personal results and a review of the literature, we report the eventual interest of surgical staging in malignant ovarian germ cell tumours. PATIENTS AND METHODS: This was a retrospective study of 36 patients (21.5-[8-61]) with malignant ovarian germ cell tumours between January 1984 and December 2004. There were 4 groups: no 1--dysgerminoma only, no 2--immature teratoma, no 3- malignant ovarian germ cell tumours with secretion. All the patients had a minimal follow up of 18 months after treatment. We reported conservative or non conservative surgery, if surgical staging was made and description of eventual neoadjuvant or adjuvant chemotherapies and finally the recurrences and deaths. RESULTS: Stages of FIGO were: group 1--IA n=2, IC n=2, IIB n=1, IIIA n=2, IIIC n=3; group 2--IA n=3 (G1, G2, G2), IC n=1 (G3); group 3--IA n=8, IC n=4, IIA n=1, IIIA n=1, IIIB n=3, IIIC n=5. Three patients had neoadjuvant chemotherapy. All the patients had cytoreductive surgery (conservative surgery n=31) with staging in 15 cases. Twenty-six patients had adjuvant chemotherapy. Five years global survival was 92%. DISCUSSION AND CONCLUSION: Surgery in a young patient with malignant ovarian germ cells tumours must be conservative (adnexectomy) (preserving fertility and because of good prognostic). In case of stage IA with part of dysgerminoma and/or immature teratoma and/or embryonal carcinoma certified by surgical staging, strict follow up could be organized (clinic, radiology, AFP, HCG). In case of more than stage IA, chemotherapy is indicated after conservative surgery and surgical staging. PMID- 17350875 TI - [Prolegomena before any psychoanalytical approach to endometriosis]. AB - Endometriosis is a disease, which requires medication or surgery to be treated. However, it can be considered as a symptom psychoanalytically speaking. Before going further into the question from this point of view, let us examine some prolegomena--preliminary principles. The scientistic ideology of a La Mettrie's "Human Machine", the unconscious subject promoted by psychoanalysts for more than a century, the Anglo-American notion of post-traumatic stress disorder, and womanhood and the mental structure customarily called hysteria stand for the main prolegomena. English and French speaking psychopathological literature is reviewed to introduce our personal experience of women with endometriosis. Finally, a public consultation is considered to confirm or invalidate scientific data stemmed from psychoanalytical experience. PMID- 17350877 TI - Mechanosensitive channel of large conductance. AB - Microbial cells constitutively express the Large Conductance Mechanosensitive Channel which opens in response to stretch forces in the lipid bilayer. The channel protein forms a homopentamer with each subunit containing two transmembrane regions and gates via the bilayer mechanism evoked by hydrophobic mismatch and changes in the membrane curvature and/or transbilayer pressure profile. During the stationary phase and during osmotic shock the channel protein is up-regulated to prevent cell lysis. Pharmacological potential of MscL may involve discovery of new age antibiotics to combat multiple drug-resistant bacterial strains. PMID- 17350876 TI - Src kinase signaling in leukaemia. AB - Role of Src kinases in acute lymphoblastic leukaemia has been recently demonstrated in leukaemia mouse model. Retained activation of Src kinases by the BCR-ABL oncoprotein in leukaemic cells following inhibition of BCR-ABL kinase activity by imatinib indicates that Src activation by BCR-ABL is independent of BCR-ABL kinase activity and provides an explanation for reduced effectiveness of the BCR-ABL kinase activity inhibitors in Philadelphia chromosome-positive acute lymphoblastic leukaemia. Simultaneous inhibition of kinase activity of both BCR ABL and Src kinases results in long-term survival of mice with acute lymphoblastic leukaemia. Leukaemic stem cells exist in acute lymphoblastic leukaemia, and complete eradication of this group of cells would provide a curative therapy for this disease. PMID- 17350878 TI - Oral cancer survival in young people in South East England. AB - The incidence rate of oral cancer among young people in the UK has been increasing since 1970s. The objective of this study was to compare relative survival of young people (under 45 years of age) diagnosed with oral cancer with that of older people (45 years and older) resident in South East England. Between 1986 and 2002, 5 year relative survival was higher among young people compared with the older group, suggesting age was a strong independent predictor of survival. Apart from age other independent predictors of survival included stage, treatment and affluence but residence was not a significant predictor of survival in either age group. For the young age group (0-44 years) mean relative survival for the period under study was relatively constant but consistently higher in younger women than in younger men. PMID- 17350879 TI - 18F-fluorodeoxyglucose-positron emission tomography and bone scintigraphy for detecting bone metastases in patients with malignancies of the upper aerodigestive tract. AB - The role of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in identifying bone metastases in patients with head and neck cancer is not clear. We compared the ability of FDG-PET and bone scintigraphy (BS) to detect bone metastases in patients with upper aerodigestive tract (UADT) malignancies. Patients with histologically confirmed malignancies in the UADT underwent both FDG-PET and BS at initial staging or follow-up. The two methods were compared in patients and in seven skeletal regions. Maximum standard uptake value (SUVmax) on PET was calculated in each lesion and compared between true- and false-positive lesions. This study included 564 eligible patients, of whom 17 had bone metastases. The spine was the most frequently involved site, followed by the lungs and liver. Both FDG-PET and BS had high specificity, accuracy, and negative predictive values for detecting bone metastases (>95% each), and the two methods did not differ in sensitivity, specificity, and predictive values (P>0.05). Both FDG-PET (n=15) and BS (n=14) yielded a significant number of false-positive results, which could be corrected by further work-ups and follow-up imaging. Compared with true-positive lesions, the false-positive lesions on FDG-PET were usually single (86.7% vs. 12.5%, P<0.001) and had lower mean SUVmax (2.4 vs. 5.6, P<0.001). FDG-PET is not more accurate than BS for detecting bone metastasis in patients with UADT cancer. Positive findings on FDG-PET or BS require further confirmation. PMID- 17350880 TI - A novel strategy for the determination of enantiomeric compositions of chiral compounds by chemometric analysis of the UV-vis spectra of bovine serum albumin receptor-ligand mixtures. AB - In this work, a novel strategy was constructed to determine the enantiomeric composition of chiral substances discriminated by bovine serum albumin (BSA) based on the UV-vis spectra of the receptor-ligand mixtures coupled with partial least squares (PLS-1) analysis. Taking tryptophan (Trp) enantiomer as an example, when 20 microM BSA was used, the enantiomeric composition was accurately determined with concentration of only 100 nM and the corresponding enantiomeric excess as high as 98% (or -98%), which is relatively more sensitive than in literature. Furthermore, the BSA-based approach was also used to predict the enantiomeric composition of other chiral compounds, such as phenylalanine (Phe), tyrosine (Tyr), alanine (Ala), cysteine (Cys), DOPA and propranolol (Prop). The results fully demonstrate that BSA is effective in determination of enantiomeric composition of some chiral compounds. PMID- 17350881 TI - Langmuir-Blodgett films of p-terphenyl in different matrices: evidence of dual excimer. AB - Langmuir-Blodgett (LB) films at different mole fractions of p-terphenyl have been prepared using two different matrices, viz., stearic acid (SA) and polymethyl methacrylate (PMMA). Multilayered LB films have been formed by changing various LB parameters namely, mole fraction of mixing, changing the number of layers as well as also the different surface pressure of lifting. The spectroscopic characteristics of mixed LB films, solution and microcrystal have been compared using UV-vis absorption and steady state fluorescence spectroscopy. Change of planarity of TP molecules are occurred while going from solution to solid states/films. Fluorescence spectra of the mixed LB films reveal intense excimeric emission in the mixed LB films with D1 excimer peak at 397 nm and D2 excimer peak at 412 nm. Various LB parameters namely changing the number of layers as well as the different surface pressure of lifting played important roles in the formation of dual excimeric sites in the mixed LB films. PMID- 17350882 TI - Normal coordinates analyses of disaccharides constituted by D-glucose, D galactose and D-fructose units. AB - A thorough study of the vibrational spectra of two disaccharides, melibiose and turanose, is presented in this work. The infrared and Raman spectra of these two compounds have been first recorded in the mid infrared range then in the far infrared region (for Raman only). These spectra constitute the main experimental support for the calculations of the modified Urey-Bradley-Shimanouchi force fields of these two disaccharides. Good agreements have been obtained between the observed and calculated frequencies. In a second time, spectra of O-deuterated derivatives have been recorded and used in order to confirm some of the frequency assignments and to test the validity of the obtained force fields. PMID- 17350883 TI - Effect of bismuth oxide on the thermal stability and Judd-Ofelt parameters of Er3+/Yb3+ co-doped aluminophosphate glasses. AB - The Er3+/Yb3+ co-doped glasses with compositions of xBi2O3-(65-x)P2O5-4Yb2O3 11Al2O3-5BaO-15Na2O (where x=0, 2.5, 5, 7.5 and 10 mol%) were prepared using the normal melt quench technique. The optical absorption spectra of the glasses were recorded in the wavelength range 300-1700 nm. The effect of Bi2O3 content on the thermal stability and absorption spectra of glasses was investigated. In addition, the Judd-Ofelt parameters and oscillator strengths were calculated by employing Judd-Ofelt theory. It was observed that the positions of the fundamental absorption edge and cut-off wavelength shifted towards red as the content of Bi2O3 increased. However, there were no red shifts found both in the peak wavelength and in the center of mass wavelength of all absorption bands with Bi2O3 content increasing. The results of Judd-Ofelt theory analysis showed that Judd-Ofelt parameters Omega t (t=2, 4, 6) changed sharply when Bi2O3 concentration exceeded 5 mol%. The variation trends of experimental oscillator strength were similar with those of Judd-Ofelt parameters as function of Bi2O3 concentrations. Moreover, differential scanning calorimetry experiments showed that the increases of Bi2O3 content weakened the network structure and then lowered the thermal stability of the glasses. The spontaneous emission probability A rad, branching ratio beta and the radiative lifetime tau rad were also calculated and analyzed. The stimulated emission cross-section of Er3+ was calculated according to the McCumber theory. It was found that the stimulated emission cross-section of Er3+ was monotonically increases with Bi2O3 content increasing. PMID- 17350884 TI - Derivative-ratio spectrophotometric method for the determination of ternary mixture of aspirin, paracetamol and salicylic acid. AB - A derivative spectrophotometric method was developed for the assay of a ternary mixture of aspirin (ASP), paracetamol (PAR) and salicylic acid (SAL). The method is based on the use of the first and second derivatives of the ratio spectra and measurement at zero-crossing wavelengths. The ratio spectra were obtained by dividing the absorption spectrum of the mixture by that of one of the components. The concentration of the other components are then determined from their respective calibration curves treated similarly. The described method was applied for the determination of these combinations in synthetic mixtures and dosage forms. The results obtained were accurate and precise. PMID- 17350885 TI - Vibrational spectra of dipropylsulfoxide. AB - FTIR and Raman spectra analysis of pure dipropylsulfoxide (DPSO), binary mixtures of DPSO/CCl(4), and DPSO/water has been first performed. The complex pattern of spectra has been explained on the basis of molecular interactions between DPSO and other molecules and, in the aqueous solutions, the role of both hydrophilic and hydrophobic interactions have been discussed depending on the concentrations. The changes in the intensities and in the frequencies of DPSO bands on concentration have been considered. The curve fitting procedure has been performed for both SO and C-H stretching region, and, on the basis of deconvolution results different type of molecular interactions have been considered. Density function theory DFT/(B3LYP) method has been used to determine the optimized geometry for free DPSO and for 1 DPSO:1 water complex. On the basis of the 6-31+G(d) quality sets parameters, the DFT calculated bond parameters and harmonic vibrations are in a very good agreement with experimental data. PMID- 17350886 TI - Acute respiratory infection by human metapneumovirus in children in southern Brazil. AB - BACKGROUND: Human metapneumovirus (hMPV) has been described as an etiologic agent of acute respiratory infections (ARI), mainly in pediatric patients. Viral isolation is difficult and has low sensitivity, and consequently RT-PCR assays are currently used for detection. OBJECTIVES: Detect hMPV in ARI in hospitalized children in Southern Brazil; standardize a RT-PCR for routine hMPV diagnosis; validate a positive control for molecular tests; and perform phylogenetics analyses. STUDY DESIGN: Nasopharyngeal aspirates (NPA) from 156 hospitalized children were studied. A conserved region of the nucleoprotein gene was cloned, characterized and used to standardize an RT-PCR assay. Phylogenetic analyses were performed. Clinical data were obtained from medical records. RESULTS: hMPV was detected in 6.4% of the samples. Dyspnea and wheezing were frequently reported symptoms and the most common diagnoses were bronchiolitis, acute respiratory insufficiency or laryngotracheobronchitis. Nucleotide sequence alignment revealed 97.7% identity with genotype A1 of hMPV. The detection limit of hMPV genomes by RT-PCR in clinical samples was 180 copies/microL. CONCLUSION: This is the first report of the detection and genetic characterization of hMPV infections in children with lower ARI in Southern Brazil. PMID- 17350887 TI - Polyunsaturated fatty acids stimulate phosphatidylcholine synthesis in PC12 cells. AB - The synthesis of phospholipids in mammalian cells is regulated by the availability of three critical precursor pools: those of choline, cytidine triphosphate and diacylglycerol. Diacylglycerols containing polyunsaturated fatty acids (PUFAs) apparently are preferentially utilized for phosphatide synthesis. PUFAs are known to play an important role in the development and function of mammalian brains. We therefore studied the effects of unsaturated, monounsaturated and polyunsaturated fatty acids on the overall rates of phospholipid biosynthesis in PC12 rat pheochromocytoma cells. Docosahexaenoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (AA, 20:4n-6) all significantly stimulated the incorporation of (14)C-choline into total cellular phospholipids. In contrast, monounsaturated oleic acid (OA) and the saturated palmitic (PA) and stearic (SA) acids did not have this effect. The action of DHA was concentration-dependent between 5 and 50 microM; it became statistically significant by 3 h after DHA treatment and then increased over the ensuing 3 h. DHA was preferentially incorporated into phosphatidylethanolamine (PE) and phosphatidylserine (PS), while AA predominated in phosphatidylcholine (PC). PMID- 17350888 TI - First case of human babesiosis in Germany - Clinical presentation and molecular characterisation of the pathogen. AB - Babesiosis is a common infection of animals and is gaining increasing attention as an emerging tick-borne zoonosis of humans in Europe. Here we report on the first case of human babesiosis in Germany in a 63-year-old splenectomised German patient with a relapse of nodular lymphocyte-predominant Hodgkin's lymphoma. After treatment with a chimeric anti-CD20 antibody preparation (Rituximab), the patient was hospitalised because of anaemia and dark urine from haemoglobinuria. Presumptive diagnosis of babesiosis was made based on piriform parasitic erythrocytic inclusions in peripheral blood smears and confirmed by Babesia specific 18S rDNA PCR. Sequence analysis revealed a >99% homology of the amplicon with the recently described EU1 organism clustering within the Babesia divergens/Babesia odocoilei complex. Despite treatment with quinine and clindamycin the patient relapsed and developed chronic parasitaemia requiring re treatment and long-term maintenance therapy with atovaquone before he eventually seroconverted and the parasite was cleared. Our findings suggest that human babesiosis occurs in Germany and can take a chronic course in immunocompromised individuals. PMID- 17350889 TI - Pacing during an elite Olympic distance triathlon: comparison between male and female competitors. AB - This study investigated whether pacing differed between 68 male and 35 female triathletes competing over the same ITU World Cup course. Swimming, cycling and running velocities (m s(-1) and km h(-1)) were measured using a global positioning system (Garmin, UK), video analysis (Panasonic NV-MX300EG), and timing system (Datasport, Switzerland). The relationship between performance in each discipline and finishing position was determined. Speed over the first 222 m of the swim was associated with position (r=-0.88 in males, r=-0.97 in females, both p<0.01) and offset from the leader, at the swim finish (r=-0.42 in males, r= 0.49 in females, both p<0.01). The latter affected which pack number was attained in bike lap 1 (r=0.81 in males, r=0.93 in females, both p<0.01), bike finishing position (both r=0.41, p<0.01) and overall finishing position (r=0.39 in males, r=0.47 in females, both p<0.01). Average biking speed, and both speed and pack attained in bike laps 1 and 2, influenced finishing position less in the males (r=-0.42, -0.2 and -0.42, respectively, versus r=-0.74, -0.75, and -0.72, respectively, in the females, all p<0.01). Average run speed correlated better with finishing position in males (r=-0.94, p<0.01) than females (r=-0.71, p<0.001). Both sexes ran faster over the first 993 m than most other run sections but no clear benefit of this strategy was apparent. The extent to which the results reflect sex differences in field size and relative ability in each discipline remains unclear. PMID- 17350890 TI - Coronary artery fistula with coronary sinus obstruction and retrograde drainage. AB - Coronary artery to coronary sinus fistula (CACSF) in association with stenosis of coronary sinus (CS) ostium and retrograde drainage via persistent left superior vena cava (LSVC) is an extremely rare anomaly presenting in the neonatal period. We report herein a 2-day-old boy with similar anomalies, who presented to us with congestive heart failure and underwent surgical repair. Echocardiography including Doppler ultrasound was a non-invasive, quick and accurate tool to diagnose each abnormality satisfactorily. This anomaly has clinical, physiological and surgical implications due to presence of altered flow pattern and variable anatomy. Therefore, such malformations need a careful assessment, preferably by non-invasive diagnostic tools, and appropriate management. PMID- 17350891 TI - Idiopathic pulmonary trunk aneurysm causing airway obstruction in an infant. AB - We report a case of idiopathic pulmonary trunk aneurysm in an infant, in which the main clinical picture was airway obstruction. Aneurysmorraphy was the chosen surgical approach and showed to be successful on 13 months follow-up. PMID- 17350892 TI - Isolation and preliminary characterization of a Cd-binding protein from Tenebrio molitor (Coleoptera). AB - The effect of cadmium (Cd) exposure on Cd-binding ligands was investigated for the first time in a beetle (Coleoptera), using the mealworm Tenebrio molitor (L) as a model species. Exposure to Cd resulted in an approximate doubling of the Cd binding capacity of the protein extracts from whole animals. Analysis showed that the increase was mainly explained by the induction of a Cd-binding protein of 7134.5 Da, with non-metallothionein characteristics. Amino acid analysis and de novo sequencing revealed that the protein has an unusually high content of the acidic amino acids aspartic and glutamic acid that may explain how this protein can bind Cd even without cysteine residues. Similarities in the amino acid composition suggest it to belong to a group of little studied proteins often referred to as "Cd-binding proteins without high cysteine content". This is the first report on isolation and peptide sequence determination of such a protein from a coleopteran. PMID- 17350893 TI - Gastrointestinal tuberculosis: an unusual presentation. PMID- 17350894 TI - Role of endoscopic ultrasound in the diagnosis of intraductal papillary mucinous neoplasms: correlation with surgical histopathology. AB - BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are precancerous tumors characterized by dilation of the main pancreatic duct, its side branches, or both. The purpose of this study was to evaluate the role of endoscopic ultrasound (EUS) in differentiating benign and malignant IPMNs. METHODS: We identified all patients between July 1996-November 2005 who underwent preoperative EUS for IPMNs. Malignancy was defined as the presence of invasive carcinoma; all other neoplasms were considered benign. The results of EUS and EUS guided fine-needle aspiration (EUS-FNA) were compared with corresponding histopathology. RESULTS: Seventy-four patients (38 male; mean age, 65 years) with 21 (28%) malignant and 53 (72%) benign IPMNs were identified. Sixty-five (88%) underwent EUS-FNA. Compared with benign tumors, patients with malignant IPMNs were more likely to be older (P = .011), present with jaundice (P = .03) or weight loss (P = .03), and have EUS features of a dilated main pancreatic duct (P = .0001), solid lesion (P = .0001), pancreatic ductal filling defects (P = .03), or thickened septa within any cyst (P = .02). The sensitivity, specificity, and accuracy of EUS-FNA for the diagnosis of malignancy were 75% (95% confidence interval [CI], 53%-89%), 91% (95% CI, 79%-97%), and 86% (95% CI, 76%-93%), respectively. Cyst or pancreatic duct fluid carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 did not differ between groups. CONCLUSIONS: Older age, jaundice and weight loss, and EUS features of a solid lesion, dilated main pancreatic duct, ductal filling defects, and thickened septa are predictive of malignancy in patients with IPMNs. EUS-FNA cytology is helpful, but cyst fluid CEA and CA 19-9 are of limited value to differentiate malignant from benign IPMNs. PMID- 17350895 TI - Duodenal thrombotic thrombocytopenic purpura. PMID- 17350896 TI - Speciation and phylogeography of the Southeast Asian Anopheles sundaicus complex. AB - Anopheles sundaicus s.l. is a malaria vector in coastal areas of Southeast Asia. Previous studies showed at least four distinct species within the complex. The present study investigated the phylogeography and the status of A. sundaicus s.l. populations from Cambodia, Thailand, Malaysia and Indonesia with regard to A. sundaicus s.s. from Sarawak, Malaysian Borneo and A. epiroticus in Vietnam and Thailand. Three lineages recovered by analyses of Cyt-b and COI (mtDNA) confirmed the presence of A. sundaicus s.s. in Malaysian Borneo, the distribution of A. epiroticus from southern Vietnam to peninsular Malaysia, and recognised a distinct form in Indonesia that is named A. sundaicus E. The phylogenetic and demographic analyses suggest that the three species were separated during the Early Pleistocene (1.8-0.78 Myr) and experienced bottlenecks followed by a genetic expansion in more recent times. Based on the results and knowledge of the biogeography of the area, we hypothesise that the combination of cyclical island and refugium creation was the cause of lineage isolation and bottleneck events during the Pleistocene. PMID- 17350897 TI - Protein influence on the plasma membrane dielectric properties: in vivo study utilizing dielectric spectroscopy and fluorescence microscopy. AB - We have investigated the origin of the dielectric response of the plasma membrane of living yeast cells (Saccharomyces cerevisiae) by using radiofrequency dielectric spectroscopy. The cells were genetically engineered to overexpress in the membrane of yeast cells a G protein-coupled receptor--the Sterile2-alpha factor receptor protein (Ste2p)--fused to the green fluorescent protein (GFP). Presence of the Ste2-GFP proteins in the plasma membrane was confirmed by exciting the cells at 476 nm and observing with a confocal microscope the emission characteristic of the GFP from individual cells. The dielectric behavior of cells suspended in KCl solution was analyzed over the frequency range 40 Hz 110 MHz and compared to the behavior of control cells that lacked the ability to express Ste2p. A two-shell electrical cell model was used to fit the data starting from known structural parameters and adjustable electrical phase parameters. The best-fit value for the relative permittivity of the plasma membrane showed no significant difference between cells expressing Ste2p (1.63+/ 0.11) and the control cells (1.75+/-0.16). This result confirmed earlier predictions that the dielectric properties of the plasma membrane in the radiofrequency range mostly reflect the properties of the hydrophobic layer of the membrane, which is populated by the hydrocarbon tails of the phospholipids and hydrophobic segments of integral membrane proteins. We discuss ways by which dielectric spectroscopy can be improved to be used for tag-free detection of proteins on the membrane. PMID- 17350898 TI - Clinical trials in cystic fibrosis. AB - In patients with cystic fibrosis (CF), clinical trials are of paramount importance. Here, the current status of drug development in CF is discussed and future directions highlighted. Methods for pre-clinical testing of drugs with potential activity in CF patients including relevant animal models are described. Study design options for phase II and phase III studies involving CF patients are provided, including required patient numbers, safety issues and surrogate end point parameters for drugs, tested for different disease manifestations. Finally, regulatory issues for licensing new therapies for CF patients are discussed, including new directives of the European Union and the structure of a European clinical trial network for clinical studies involving CF patients is proposed. PMID- 17350899 TI - Interactions of serum with lung surfactant extract in the bronchiolar and alveolar airway models. AB - Lung surfactant (LS) a lipid-protein mixture is secreted by type-II pneumocytes and prevents alveolar collapse as well as maintains upper airway patency. In certain lung pathophysiology dysfunction of the LS occurs due to leakage of serum derived materials interacting with surfactant at the respiratory air-water interface. Bovine lipid extract surfactant (BLES) with and without foetal calf serum (FCS) were studied as models of bronchiolar airway patency using a capillary surfactometer, and in alveolar (terminal) airway using adsorbed Langmuir films in a surface balance. About 5 wt.% of serum was found to maximally decrease airway patency of BLES by 90%, as well as the surface films ability to reach low surface tension below 25 mN/m. In fact, FCS was found to be about 200 fold more potent inhibitor of the surfactant extract compared to a major serum component, albumin. Also serum but not albumin significantly reduced the gel phase structures found in BLES films under compression at low amounts (5-10 wt.%), and eventually abolished these organized structures as imaged by fluorescence and atomic force microscopy. This fact suggests that serum caused complete molecular re-organization of the surfactant lipids in films at an air water interface, and the ability of such films to reduce surface tension or maintain airway patency. The study may provide a novel structure-function disruption model for lung surfactant inactivation in the airways in pathophysiology. PMID- 17350900 TI - Cardiovascular proteomic analysis. AB - Here, we report on our proteomic studies in the field of cardiovascular medicine. Our research has been focused on understanding the role of proteins in cardiovascular disease with a particular focus on epigenetic regulation and biomarker discovery, with the objective of better understanding cardiovascular pathophysiology to lead to the development of new and better diagnostic and therapeutic methods. We have used mass spectrometry for over 5 years as a viable method to investigate protein-protein interactions and post-translational modifications in cellular proteins as well as a method to investigate the role of extra-cellular proteins. Use of mass spectrometry not only as a research tool but also as a potential diagnostic tool is a topic of interest. In addition to these functional proteomics studies, structural proteomic studies are also done with expectations to allow for pinpoint drug design and therapeutic intervention. Collectively, our proteomics studies are focused on understanding the functional role and potential therapeutically exploitable property of proteins in cardiovascular disease from both intra-cellular and extra-cellular aspects with both functional as well as structural proteomics approaches to allow for comprehensive analysis. PMID- 17350901 TI - Development and validation of a liquid chromatography-tandem mass spectrometric method for the determination of the major metabolites of duloxetine in human plasma. AB - A sensitive bioanalytical method for the measurement of two major circulating metabolites of duloxetine [4-hydroxy duloxetine glucuronide (LY550408) and 5 hydroxy-6-methoxy duloxetine sulfate (LY581920)] in plasma is reported. This method produced acceptable precision and accuracy over the validation range of 1 1000 ng/mL. Several issues had to be addressed in order to develop an LC/MS/MS assay for these metabolites. First, 4-hydroxy duloxetine glucuronide required chromatographic resolution from the 5-, and 6-hydroxy duloxetine glucuronide isomers. Second, the glucuronide conjugate is readily ionized under positive ESI conditions, while the sulfate conjugate required negative ESI conditions to obtain adequate sensitivity. Finally, the chromatographic conditions needed to separate the glucuronide isomers were not suitable for the analysis of the sulfate conjugate. The present method addressed these challenges, and was successfully applied to multiple human pharmacokinetic studies in which subjects received oral doses of duloxetine hydrochloride. PMID- 17350902 TI - Determination of N-acetyl retigabine in dog plasma by LC/MS/MS following off-line microElution 96-well solid phase extraction. AB - A high throughput off-line microElution 96-well solid phase extraction (SPE) followed by liquid chromatography with tandem mass spectrometry (LC/MS/MS) quantification for the determination of N-acetyl retigabine in dog plasma has been developed and validated. The method involves the use of microElution 96-well SPE for the simultaneous extraction of N-acetyl retigabine and rapid removal of its N-glucuronide metabolite that has shown to be problematic due to its instability using other clean-up methods. The microElution SPE technology eliminates the need for post-extraction solvent evaporation and greatly reduces sample preparation time consequently improving assay efficiency. PMID- 17350903 TI - Relationship between MPA free fraction and free MPAG concentrations in heart transplant recipients based on simultaneous HPLC quantification of the target compounds in human plasma. AB - A simple and sensitive HPLC method for the simultaneous analysis of free MPA and free MPAG was developed. Separation was achieved on a X-Terra RP18 column with acetonitrile-40 mM orthophosphoric acid as eluents using a gradient elution mode over 35 min at a flow rate of 1.5 ml/min. The assay was linear in the range 0.005 mg/L (LOQ) to 5mg/L for free MPA and 0.05 mg/L (LOQ) to 200 mg/L for free MPAG. Isolation of free MPA and free MPAG was done by ultrafiltration and the ultrafiltrate was directly injected. A positive correlation between MPA free fractions and free MPAG concentrations was found. Likewise, free MPAG was related to total MPAG concentrations in the seven heart transplant patients. PMID- 17350904 TI - Ultra sensitive determination of limaprost, a prostaglandin E1 analogue, in human plasma using on-line two-dimensional reversed-phase liquid chromatography-tandem mass spectrometry. AB - A highly sensitive and selective method has been developed and validated to determine limaprost, a prostaglandin (PG) E(1) analogue, in human plasma by on line two-dimensional reversed-phase liquid chromatography-tandem mass spectrometry (2D-LC/MS/MS) due to the lack of efficient methods to determine very low levels of limaprost in plasma. Limaprost and its deuterium derivatives, used as internal standard, were extracted by protein precipitation and following three step solid phase extractions. After extraction procedure, samples were analyzed by on-line 2D-LC/MS/MS with electrospray ionization in negative mode. The 2D-LC system consists of Phenyl column at first dimension and ODS at second dimension with a trapping column placed between the separation columns. The linear dynamic range of this method was 0.1-10 pg/ml with 3 ml of plasma (r >0.9987). Acceptable precision and accuracy were obtained over the calibration curve ranges. The assay has been successfully used in analyses of human plasma samples to support clinical pharmacokinetics studies. PMID- 17350905 TI - HPLC determination of midazolam and its three hydroxy metabolites in perfusion medium and plasma from rats. AB - A new, simple, rapid, sensitive, and repeatable isocratic reverse-phase HPLC method was developed and validated for simultaneous determination of midazolam and its main three hydroxylated metabolites, i.e. 1'-hydroxymidazolam, 4 hydroxymidazolam, and 1',4-dihydroxymidazolam in rat liver perfusate and also plasma. Diazepam was used as an internal standard to ensure precision and accuracy of this method. Analytes were extracted from alkalinized samples into diethyl ether using single-step liquid-liquid extraction. A C18 analytical column and a mobile phase composed of acetonitrile and sodium acetate buffer were used for the chromatographic separation with UV detection. Limits of detection varied between 7.9 and 19.6 microg/L for midazolam and its hydroxy metabolites. The overall recovery for the analytes exceeded 92%, for concentrations twice the limits of detection. The intra- and inter-day precision at three different concentrations never exceeded 8 and 11% variation, respectively. This method is applicable for modeling and description of possible pharmacological interactions on rat (CYP3A1/2) or human (CYP3A4/5) cytochrome P450 enzymes. PMID- 17350906 TI - Studies on endotoxin removal mechanism of adsorbents with amino acid ligands. AB - In this paper, a series of adsorbents with different amino acid ligands for endotoxin removal were prepared and endotoxin adsorption capacities (EAC) in aqueous solution were studied using an affinity column. The results showed that the property and structure of amino acid ligands have great influence on EAC. As the increasing of isoelectric point and polarity of amino acids ligands, EACs of the adsorbents increased. In addition, computer simulation method was employed to a further investigation on the interaction between endotoxins and ligands. Based on the results, some adsorbents were applied to remove endotoxin from endotoxemia rabbit's serum. Similar adsorption results were observed and the removal efficiency of adsorbents with Arg, Ser ligands is up to 78%. PMID- 17350907 TI - Fluorescence spectroscopic analysis of the proximity changes between the central helix of troponin C and the C-terminus of troponin T from chicken skeletal muscle. AB - Recent structural studies of the troponin (Tn) core complex have shown that the regulatory head containing the N-lobe of TnC is connected to the IT arm by a flexible linker of TnC. The IT arm is a long coiled-coil formed by alpha-helices of TnI and TnT, plus the C-lobe of TnC. The TnT is thought to play a pivotal role in the linking of Ca(2+) -triggered conformational changes in thin filament regulatory proteins to the activation of cross-bridge cycling. However, a functional domain at the C-terminus of TnT is missing from the Tn core complex. In this study, we intended to determine the proximity relationship between the central helix of TnC and the TnT C-terminus in the binary and the ternary complex with and without Ca2+ by using pyrene excimer fluorescence spectroscopy and fluorescence resonance energy transfer. Chicken fast skeletal TnC contains a Cys102 at the E helix, while TnT has a Cys264 at its C-terminus. These two cysteines were specifically labeled with sulfhydryl-reactive fluorescence probes. The measured distance in the binary complex was about 19 Angstroms and slightly increased when they formed the ternary complex with TnI (20 Angstroms). Upon Ca2+ binding the distance was not affected in the binary complex but increased by approximately 4 Angstroms in the ternary complex. These results suggest that TnI plays an essential role in the Ca(2+) -mediated change in the spatial relationship between the C-lobe of TnC and the C-terminus of TnT. PMID- 17350908 TI - [The state of the organized screening in Hungary in 2006]. AB - Hungary carries a heavy burden of cancer. At present, the organized screening of symptomless people seems to be the most promising strategy. According to the state-of-the art, those are the mammography-based breast screening, the cytology screening of cervix uteri, and the colorectal screening using immunochemical detection of the fecal occult blood satisfy the criteria of organized screening. The screening for cancers of the oral cavity, and the methods suitable for early detection of prostate cancer are not based on epidemiological evidence, therefore can only be applied opportunistically, as part of the medical practice. For the time belong, there are no suitable methods for detection of early lung cancer. The organized screening which applies personal call-and-recall has been incorporated in the National Public Health Programme. The concepts underlying the organized screening are fully in accordance with the recommendations by the European Union. The Chief Medical Officers' Office (OTH) is being charged with the organization, coordination and evaluation of organized screening programmes for the above screening modalities. In the past few years, an appropriate system for administration and information (including a country-wide screening registry) has been established, in addition to a regional coordination system based on the institutes of National Public Health and Medical Officers' Service (ANTSZ) and a nation-wide network of mammography and cytological laboratories, capable of meeting the requirements. This publication is to summarize the problems yet to be solved and the results expected from the organized screening programmes. PMID- 17350909 TI - [Paper and/or online journals?]. PMID- 17350910 TI - [The effects of drug-eluting coronary stents]. AB - (Drug-eluting stents substantially reduce the incidence of restenosis after percutaneous coronary interventions.) The cytostatic drugs however not only inhibit the proliferation of smooth muscle cell and neointima proliferation but also delay the endothelisation of the stent struts. It may result in persistent inflammatory reaction and also in stent thrombosis. The trials comparing the efficacy of drug-eluting and bare metal stents, and also that of the two drug eluting stent brands are reviewed. The efficacy of the two brands of drug-eluting stents in prevention of restenosis is almost equal. Late stent thrombosis is more frequent after drug eluting, than after bare metal stents. This rare, but severe complication may develop if drug-eluting stents are used in off-label indications and anatomic situations. In order to avoid late stent thrombosis devices should be used as labelled, the platelet inhibitory treatment should be more efficacious and longlasting than these days. Thorough information about the importance of adherence to prescribed treatment should be delivered to the patients and to the medical community as well. PMID- 17350911 TI - [Increase of muscle mass and strength with hormones and other drugs, combined with physical training]. AB - Increasing muscle mass and strength is the aim of some body builders and sportsmen, and is a therapeutic target in hormonal deficiencies, as well as in many clinical situations, when muscle devastation is a life-limiting factor. Human growth hormone, insulin-like growth factor, anabolic-androgen steroids and regulating proteins influencing muscle development and differentiation are used also for delaying the aging processes. Some of the practices are hailed by several myths, mainly because doping cases in certain competitive sports. Physiology, and therapeutic experiences with these substances are reviewed with special reference to physical exercise and to some frail conditions. PMID- 17350912 TI - [Hydrops fetalis--a retrospective study]. AB - In a retrospective study, the authors examined the occurrence of hydrops in foetal and neonatal cases in a five-year period. During this time, the clinical and pathologic diagnosis of hydrops was established in 28 cases. In three cases, the hydrops was caused by Rh incompatibility, and in 25 cases non-immune hydrops was discovered by clinical and pathologic examination. The cause of hydrops was recognised in 25 cases and no underlying disease was discernible in three. In 12 cases, the pregnancy was spontaneously terminated. Artificial abortion was performed in four cases. In this series, four hydropic newborns died on the first week of their life. The average age in artificial abortion was 16-20 gestational week and 24 in spontaneous abortion or stillbirth. Pathologic examination revealed increased weight, oedema, ascites, and hydrothorax in all cases. In half of the cases, there was also hydropericardium. Hepatosplenomegaly, cardiomegaly, pulmonary hypoplasia, increased extramedullary hemopoiesis, and placenta oedema were seen in all the cases. Causes of the non-immune hydrops were cardiac malformation in 4 cases, chromosome anomaly in 3, cystic hygroma in 2, skeletal anomaly in 1, foeto-foetal transfusion in 3, infection in 7 and sacrococcygeal teratoma in 1 case. In two cases, the underlying disease was reported to be of maternal origin. Comparing the clinical and pathologic findings there were only three cases with absolute agreement. The underlying disease revealed by pathologic examination was regarded to be significant from respect of inheritance, therapeutic approach, and further management in 10 cases. The authors emphasise the importance of pathologic examinations in foetal hydrops and point out the significance of clinico-pathological collaboration in the decision about further management of hydropic foetuses. PMID- 17350913 TI - [Mihaly Lenhossek, Editor-in-Chief of the Orvosi Hetilap, 1905-1922]. PMID- 17350914 TI - [Pediatrics (1898-1905), one of the supplements to the Orvosi Hetilap]. PMID- 17350919 TI - [Determining factors of cardiac biomarkers in hemodialysed diabetic and non diabetic patients]. AB - INTRODUCTION: Cardiovascular diseases are highly prevalent in chronic renal failure patients, especially in diabetic population. Cardiac biomarkers such as pro-brain natriuretic peptide N-terminal piece (NT-proBNP), cardiac troponin T (cTnT) and high sensitive CRP (hs-CRP) are increasingly used for early detection. AIMS: The authors analysed, which factors influence cardiac biomarker levels in hemodialysed patients and whether these factors depend on the presence of diabetes. METHODS: In 28 diabetic and 40 non-diabetic patients on chronic hemodialysis was analysed the association between routine laboratory data, bioimpedance parameters, results of echocardiography and ambulatory blood pressure monitoring on cardiac biomarkers. Multivariate linear regression analysis (ANOVA) was applied for statistical evaluation. RESULTS: The authors found stronger correlation (p = 0.034 vs. p = 0.001) between NT-proBNP and extracellular volume/total water volume hyperhydration ratio (ecv/twv) evaluated in diabetics than in non-diabetics. In case of cTnT, no relation was found with CaxP, iPTH, Kt/V, beta2-microglobulin, and serum uric acid levels. The hs-CRP was correlated with total cholesterol (p = 0.039) and EPO-dose (p = 0.03) in diabetics, while with serum fibrinogen (p = 0.025) in non-diabetics. The HbA1c didn't influence biomarkers in the diabetic group. CONCLUSIONS: The factors having an impact on cardiac biomarker levels are similar in diabetic and non diabetic hemodialysed patients. According to results the presence of end-stage renal disease in a cross-sectional survey probably overcomes the impact of diabetes and quality of glycaemic control on cardiac biomarker levels. PMID- 17350920 TI - [Treatment of hepatitis C in patients on renal replacement therapy]. AB - The prevalence of hepatitis C virus infection among patients on hemodialysis is about ten times higher than in the normal population. The infection can induce chronic glomerulonephritis, as an extrahepatic manifestation, which can lead to end stage renal disease. However, in the majority of the patients hepatitis C virus is acquired as a nosocomial infection during the hemodialysis. In most of the infected patients the liver enzymes are usually normal and need regular screening of the hepatitis C antibody to detect the infection. Despite of the normal liver enzymes, the liver disease may progress to cirrhosis. A part of the patients wait for renal transplantation. The immunosuppressive treatment after the renal transplantation results in a significantly increased viral replication which might induce further progression of the liver disease. Interferon treatment given after the transplantation can induce rejection and graft failure. Therefore the antiviral treatment should be administered during the hemodialysis or earlier. Only limited data are available with the treatment of patients with impaired renal function. Mostly alfa-interferon was used in these patients. Due to the impaired renal clearance and higher serum concentration interferon seems to be more effective, but less tolerable in patients with end stage renal disease than in normal patients. Ribavirin is also excreted exclusively by the kidney and the anemia is even more pronounced in these patients, therefore it is contraindicated in patients on hemodialysis. The pharmacokinetics of the pegylated interferon alfa-2a is very advantageous for the patients with end stage renal disease. The safety and efficacy of peginterferon alfa-2a is now being confirmed in many publications. PMID- 17350921 TI - [Non invasive detection of fetal Rh using real-time PCR method]. AB - INTRODUCTION: In the last ten years the detection of fetal origin cells and cell free fetal DNA in maternal circulation opened new horizons in non-invasive prenatal diagnosis. The diagnostic possibilities are based on the differences between the maternal and fetal origin DNA. One of the differences could be the Rh blood group and the genetical background. The Rh incompatibility is the most frequent blood group incompatibilities in the clinical practice, which can cause fetal anemia, hydrops and even fetal death. AIMS: The aim of this study was to detect the fetal DNA in maternal circulation, to determine the Rh status of the fetus, and to compare the reliability of the method with the data found in other studies. METHODS: Blood samples and amnionic fluid samples were collected from 30 pregnant women, with Rh negative status, between 11-22 week of gestation presented for genetic amniocentesis at the 1st. Department of Obstetrics and Gynecology, Semmelweis University. After DNA isolation real-time PCR was performed in order to detect the exon 7 of the RhD gene located on the first chromosome (1p36.11.). RESULTS: In 24 cases the PCR reaction gave same result in case of the DNA isolated from plasma and amniotic fluid, but in six cases there was no PCR product of plasma samples and the product was detectable in amniotic fluid samples. The exon 7 was detectable in 25 cases, and there was no product in 5 cases. CONCLUSIONS: The real-time PCR method seems to be an easy and reliable method to determine the fetal Rh blood group. The sensitivity and specificity of the method in this study is in concordance with international data. The use of more than one probe could increase the sensitivity of the method. PMID- 17350922 TI - [Treatment of extra-esophageal variceal bleeding with cyanoacrylate]. AB - BACKGROUND AND AIMS: Endoscopic obliteration of bleeding extra-esophageal varices using N-butyl-2-cyanoacrylate (Histoacryl) has been validated by several authors. The aim of the present paper is to describe the intravariceal injection technique using cyanoacrylate and to present the own results and complications observed in conjunction with the haemostatic treatment. PATIENTS AND METHODS: A total of 11 intravariceal injection treatments of N-butil-2-cyanoacrylate were performed in 8 patients (3 males, 5 females, mean age 65.5 years) with extra-esophageal variceal bleeding. In 7 cases the bleeding varices were located in the gastric fundus and in one case the varix was found in the duodenum. Variceal bleeders under subintensive care were treated early electively with 1:1 ratio cyanoacrylate lipiodol intravariceal injection solutions. The injection needle was inserted trough a standard endoscope. RESULTS: Early haemostasis was achieved in all patients (11/11) and no early rebleeding occurred. In one case because of repeated episodes of late recurrent bleedings 3 more injection treatments were performed. In another case several hours after the injection a transitional cerebral ischemic attack developed. Injection needle sticking occurred during one treatment. There was no mortality due to acute bleeding while two patients died because of hepatic failure during the follow up period. CONCLUSIONS: Endoscopic injection of diluted cyanoacrylate and lipiodol appears to be an effective and safe treatment method of the extra-esophageal variceal bleeding. Injection treatment in an early elective fashion can be performed with the standard sclerotherapy equipment. PMID- 17350923 TI - [Psychiatric disorders leading to noncompliance in a consultative psychiatric practice]. AB - INTRODUCTION: Noncompliance is a complex problem which can appear in each phase of the medical treatment. Lack of cooperation can cause difficulties in the examinations, during the invasive interventions following the diagnostic process, and also in the pharmacological treatment. Among the reasons leading to noncompliance, psychiatric disorders concomitant with somatic disturbances play a major role. AIM: To study the most common psychiatric disorders leading to noncooperative behavior through the examination of those cases, in which the reason of the psychiatric consultation was noncompliance. METHOD: The documentation of a five years period's consultations was retrospectively studied in the Consultation-Liaison Psychiatric Service of Szt. Laszlo Hospital. In this publication we discuss those consultations which were requested because of noncompliance. RESULTS: Dementia (27.3%) and affective disorders (40.9%) were most commonly diagnosed in noncompliance patients. Diabetes, pulmonary and renal failures were more frequent in noncompliance patients than in the whole consulted patient group. CONCLUSIONS: As comorbid depression is appearing more frequently in chronically ill patients, and because noncompliance is more frequent in depressed individuals, screening of depression in patients with diabetes, pulmonary and renal failure is a good chance in the prevention of noncompliance. PMID- 17350924 TI - [Shwachman-Diamond syndrome: clinical manifestations and molecular genetics]. AB - The Shwachman-Diamond syndrome is a rare, autosomal recessive primary immunodeficiency disorder characterized by exocrine pancreatic insufficiency, metaphyseal dysostosis, short stature, bone marrow dysfunction and recurrent infections. The authors summarize current knowledge on molecular pathomechanisms, diagnostic criteria, therapy, and clinical manifestations of the syndrome. They present the first Hungarian patient with Shwachman-Diamond syndrome, in whom mutation analysis was performed. The patient had neutropenia, exocrine pancreatic failure, severe growth retardation, and recurrent skin and respiratory tract infections. Two previously undescribed mutations in the Shwachman-Diamond syndrome gene (c.362A > C, p.N121T and c.523C > T, p.R175W) were found. Recently, the mother became pregnant again and requested prenatal diagnosis, which revealed a carrier status of the c.523C > T, (p.R175W) mutation only, so the mother decided to complete the pregnancy. PMID- 17350925 TI - [Rotavirus infection]. PMID- 17350928 TI - An analysis of amino acid sequences surrounding archaeal glycoprotein sequons. AB - Despite having provided the first example of a prokaryal glycoprotein, little is known of the rules governing the N-glycosylation process in Archaea. As in Eukarya and Bacteria, archaeal N-glycosylation takes place at the Asn residues of Asn-X-Ser/Thr sequons. Since not all sequons are utilized, it is clear that other factors, including the context in which a sequon exists, affect glycosylation efficiency. As yet, the contribution to N-glycosylation made by sequon-bordering residues and other related factors in Archaea remains unaddressed. In the following, the surroundings of Asn residues confirmed by experiment as modified were analyzed in an attempt to define sequence rules and requirements for archaeal N-glycosylation. PMID- 17350929 TI - Widespread distribution of archaeal reverse gyrase in thermophilic bacteria suggests a complex history of vertical inheritance and lateral gene transfers. AB - Reverse gyrase, an enzyme of uncertain funtion, is present in all hyperthermophilic archaea and bacteria. Previous phylogenetic studies have suggested that the gene for reverse gyrase has an archaeal origin and was transferred laterally (LGT) to the ancestors of the two bacterial hyperthermophilic phyla, Thermotogales and Aquificales. Here, we performed an in depth analysis of the evolutionary history of reverse gyrase in light of genomic progress. We found genes coding for reverse gyrase in the genomes of several thermophilic bacteria that belong to phyla other than Aquificales and Thermotogales. Several of these bacteria are not, strictly speaking, hyperthermophiles because their reported optimal growth temperatures are below 80 degrees C. Furthermore, we detected a reverse gyrase gene in the sequence of the large plasmid of Thermus thermophilus strain HB8, suggesting a possible mechanism of transfer to the T. thermophilus strain HB8 involving plasmids and transposases. The archaeal part of the reverse gyrase tree is congruent with recent phylogenies of the archaeal domain based on ribosomal proteins or RNA polymerase subunits. Although poorly resolved, the complete reverse gyrase phylogeny suggests an ancient acquisition of the gene by bacteria via one or two LGT events, followed by its secondary distribution by LGT within bacteria. Finally, several genes of archaeal origin located in proximity to the reverse gyrase gene in bacterial genomes have bacterial homologues mostly in thermophiles or hyperthermophiles, raising the possibility that they were co-transferred with the reverse gyrase gene. Our new analysis of the reverse gyrase history strengthens the hypothesis that the acquisition of reverse gyrase may have been a crucial evolutionary step in the adaptation of bacteria to high-temperature environments. However, it also questions the role of this enzyme in thermophilic bacteria and the selective advantage its presence could provide. PMID- 17350930 TI - AMP-forming acetyl-CoA synthetases in Archaea show unexpected diversity in substrate utilization. AB - Adenosine monophosphate (AMP)-forming acetyl-CoA synthetase (ACS; acetate:CoA ligase (AMP-forming), EC 6.2.1.1) is a key enzyme for conversion of acetate to acetyl-CoA, an essential intermediate at the junction of anabolic and catabolic pathways. Phylogenetic analysis of putative short and medium chain acyl-CoA synthetase sequences indicates that the ACSs form a distinct clade from other acyl-CoA synthetases. Within this clade, the archaeal ACSs are not monophyletic and fall into three groups composed of both bacterial and archaeal sequences. Kinetic analysis of two archaeal enzymes, an ACS from Methanothermobacter thermautotrophicus (designated as MT-ACS1) and an ACS from Archaeoglobus fulgidus (designated as AF-ACS2), revealed that these enzymes have very different properties. MT-ACS1 has nearly 11-fold higher affinity and 14-fold higher catalytic efficiency with acetate than with propionate, a property shared by most ACSs. However, AF-ACS2 has only 2.3-fold higher affinity and catalytic efficiency with acetate than with propionate. This enzyme has an affinity for propionate that is almost identical to that of MT-ACS1 for acetate and nearly tenfold higher than the affinity of MT-ACS1 for propionate. Furthermore, MT-ACS1 is limited to acetate and propionate as acyl substrates, whereas AF-ACS2 can also utilize longer straight and branched chain acyl substrates. Phylogenetic analysis, sequence alignment and structural modeling suggest a molecular basis for the altered substrate preference and expanded substrate range of AF-ACS2 versus MT ACS1. PMID- 17350931 TI - SSoNDelta and SSoNDeltalong: two thermostable esterases from the same ORF in the archaeon Sulfolobus solfataricus? AB - Previously, we reported from the Sulfolobus solfataricus open reading frame (ORF) SSO2517 the cloning, overexpression and characterization of an esterase belonging to the hormone-sensitive lipase (HSL) family and apparently having a deletion at the N-terminus, which we named SSoNDelta. Searching the recently reported Sulfolobus acidocaldarius genome by sequence alignment, using SSO2517 as a query, allowed identity of a putative esterase (ORF SAC1105) sharing high sequence similarity (82%) with SSO2517. This esterase displays an N-terminus and total length similar to other known esterases of the HSL family. Analysis of the upstream DNA sequence of SS02517 revealed the possibility of expressing a longer version of the protein with an extended N-terminus; however, no clear translation signal consistent with a longer protein version was detected. This new version of SSO2517 was cloned, over-expressed, purified and characterized. The resulting protein, named SSoNDeltalong, was 15-fold more active with the substrate p nitrophenyl hexanoate than SSoNDelta. Furthermore, SSoNDeltalong and SSoNDelta displayed different substrate specificities for triacylglycerols. These results and the phylogenetic relationship between S. solfataricus and S. acidocaldarius suggest a common origin of SSO2517 and SAC1105 from an ancestral gene, followed by divergent evolution. Alternatively, a yet-to-be discovered mechanism of translation that directs the expression of SSoNDeltalong under specific metabolic conditions could be hypothesized. PMID- 17350932 TI - Lineage-specific partitions in archaeal transcription. AB - The phylogenetic distribution of the components comprising the transcriptional machinery in the crenarchaeal and euryarchaeal lineages of the Archaea was analyzed in a systematic manner by genome-wide profiling of transcription complements in fifteen complete archaeal genome sequences. Initially, a reference set of transcription-associated proteins (TAPs) consisting of sequences functioning in all aspects of the transcriptional process, and originating from the three domains of life, was used to query the genomes. TAP-families were detected by sequence clustering of the TAPs and their archaeal homologues, and through extensive database searching, these families were assigned a function. The phylogenetic origins of archaeal genes matching hidden Markov model profiles of protein domains associated with transcription, and those encoding the TAP homologues, showed there is extensive lineage-specificity of proteins that function as regulators of transcription: most of these sequences are present solely in the Euryarchaeota, with nearly all of them homologous to bacterial DNA binding proteins. Strikingly, the hidden Markov model profile searches revealed that archaeal chromatin and histone-modifying enzymes also display extensive taxon-restrictedness, both across and within the two phyla. PMID- 17350933 TI - The genome of Hyperthermus butylicus: a sulfur-reducing, peptide fermenting, neutrophilic Crenarchaeote growing up to 108 degrees C. AB - Hyperthermus butylicus, a hyperthermophilic neutrophile and anaerobe, is a member of the archaeal kingdom Crenarchaeota. Its genome consists of a single circular chromosome of 1,667,163 bp with a 53.7% G+C content. A total of 1672 genes were annotated, of which 1602 are protein-coding, and up to a third are specific to H. butylicus. In contrast to some other crenarchaeal genomes, a high level of GUG and UUG start codons are predicted. Two cdc6 genes are present, but neither could be linked unambiguously to an origin of replication. Many of the predicted metabolic gene products are associated with the fermentation of peptide mixtures including several peptidases with diverse specificities, and there are many encoded transporters. Most of the sulfur-reducing enzymes, hydrogenases and electron-transfer proteins were identified which are associated with energy production by reducing sulfur to H(2)S. Two large clusters of regularly interspaced repeats (CRISPRs) are present, one of which is associated with a crenarchaeal-type cas gene superoperon; none of the spacer sequences yielded good sequence matches with known archaeal chromosomal elements. The genome carries no detectable transposable or integrated elements, no inteins, and introns are exclusive to tRNA genes. This suggests that the genome structure is quite stable, possibly reflecting a constant, and relatively uncompetitive, natural environment. PMID- 17350934 TI - Gene decay in archaea. AB - The gene-dense chromosomes of archaea and bacteria were long thought to be devoid of pseudogenes, but with the massive increase in available genome sequences, whole genome comparisons between closely related species have identified mutations that have rendered numerous genes inactive. Comparative analyses of sequenced archaeal genomes revealed numerous pseudogenes, which can constitute up to 8.6% of the annotated coding sequences in some genomes. The largest proportion of pseudogenes is created by gene truncations, followed by frameshift mutations. Within archaeal genomes, large numbers of pseudogenes contain more than one inactivating mutation, suggesting that pseudogenes are deleted from the genome more slowly in archaea than in bacteria. Although archaea seem to retain pseudogenes longer than do bacteria, most archaeal genomes have unique repertoires of pseudogenes. PMID- 17350935 TI - Assimilation of ammonium ions and reutilization of nitrogen in rice (Oryza sativa L.). AB - A major source of inorganic nitrogen for rice plants grown in paddy soil is ammonium ions. The ammonium ions are actively taken up by the roots via ammonium transporters and subsequently assimilated into the amide residue of glutamine (Gln) by the reaction of glutamine synthetase (GS) in the roots. The Gln is converted into glutamate (Glu), which is a central amino acid for the synthesis of a number of amino acids, by the reaction of glutamate synthase (GOGAT). Although a small gene family for both GS and GOGAT is present in rice, ammonium dependent and cell type-specific expression suggest that cytosolic GS1;2 and plastidic NADH-GOGAT1 are responsible for the primary assimilation of ammonium ions in the roots. In the plant top, approximately 80% of the total nitrogen in the panicle is remobilized through the phloem from senescing organs. Since the major form of nitrogen in the phloem sap is Gln, GS in the senescing organs and GOGAT in developing organs are important for nitrogen remobilization and reutilization, respectively. Recent work with a knock-out mutant of rice clearly showed that GS1;1 is responsible for this process. Overexpression studies together with age- and cell type-specific expression strongly suggest that NADH GOGAT1 is important for the reutilization of transported Gln in developing organs. The overall process of nitrogen utilization within the plant is discussed. PMID- 17350936 TI - Common mycorrhizal networks provide a potential pathway for the transfer of hydraulically lifted water between plants. AB - Plant roots may be linked by shared or common mycorrhizal networks (CMNs) that constitute pathways for the transfer of resources among plants. The potential for water transfer by such networks was examined by manipulating CMNs independently of plant roots in order to isolate the role(s) of ectomycorrhizal (EM) and arbuscular mycorrhizal fungal (AMF) networks in the plant water balance during drought (soil water potential -5.9 MPa). Fluorescent tracer dyes and deuterium enriched water were used to follow the pathways of water transfer from coastal live oak seedlings (Quercus agrifolia Nee; colonized by EM and AMF) conducting hydraulic lift (HL) into the roots of water-stressed seedlings connected only by EM (Q. agrifolia) or AMF networks (Q. agrifolia, Eriogonum fasciculatum Benth., Salvia mellifera Greene, Keckiella antirrhinoides Benth). When connected to donor plants by hyphal linkages, deuterium was detected in the transpiration flux of receiver oak plants, and dye-labelled extraradical hyphae, rhizomorphs, mantles, and Hartig nets were observed in receiver EM oak roots, and in AMF hyphae of Salvia. Hyphal labelling was scarce in Eriogonum and Keckiella since these species are less dependent on AMF. The observed patterns of dye distribution also indicated that only a small percentage of mycorrhizal roots and extraradical hyphae were involved with water transfer among plants. Our results suggest that the movement of water by CMNs is potentially important to plant survival during drought, and that the functional ecophysiological traits of individual mycorrhizal fungi may be a component of this mechanism. PMID- 17350937 TI - Is there evidence for convergent evolution around human microsatellites? AB - A study by Vowles and Amos (2004) identified atypical patterns of base composition around human microsatellites and argued that microsatellites generate mutational biases in their flanking regions. Here, we perform simulations of molecular evolution using a simple model that suggest similar patterns can be produced without any such biases in genome evolution. PMID- 17350938 TI - A very high fraction of unique intron positions in the intron-rich diatom Thalassiosira pseudonana indicates widespread intron gain. AB - Although spliceosomal introns are present in all characterized eukaryotes, intron numbers vary dramatically, from only a handful in the entire genomes of some species to nearly 10 introns per gene on average in vertebrates. For all previously studied intron-rich species, significant fractions of intron positions are shared with other widely diverged eukaryotes, indicating that 1) large numbers of the introns date to much earlier stages of eukaryotic evolution and 2) these lineages have not passed through a very intron-poor stage since early eukaryotic evolution. By the same token, among species that have lost nearly all of their ancestral introns, no species is known to harbor large numbers of more recently gained introns. These observations are consistent with the notion that intron-dense genomes have arisen only once over the course of eukaryotic evolution. Here, we report an exception to this pattern, in the intron-rich diatom Thalassiosira pseudonana. Only 8.1% of studied T. pseudonana intron positions are conserved with any of a variety of divergent eukaryotic species. This implies that T. pseudonana has both 1) lost nearly all of the numerous introns present in the diatom-apicomplexan ancestor and 2) gained a large number of new introns since that time. In addition, that so few apparently inserted T. pseudonana introns match the positions of introns in other species implies that insertion of multiple introns into homologous genic sites in eukaryotic evolution is less common than previously estimated. These results suggest the possibility that intron-rich genomes may have arisen multiple times in evolution. These results also provide evidence that multiple intron insertion into the same site is rare, further supporting the notion that early eukaryotic ancestors were very intron rich. PMID- 17350940 TI - Intensity modulating and other radiation therapy devices for dose painting. AB - The introduction of intensity-modulated radiation therapy (IMRT) in the early 1990s created the possibility of generating dramatically improved dose distributions that could be tailored to fit a complex geometric arrangement of targets that push against or even surround healthy critical structures. IMRT is a new treatment paradigm that goes beyond the capabilities of the earlier technology called three-dimensional radiation therapy (3DCRT). IMRT took the older approach of using fields that conformed to the silhouette of the target to deliver a relatively homogeneous intensity of radiation and separated the conformal fields into many subfields so that intensity could be varied to better control the final dose distribution. This technique makes it possible to generate radiation dose clouds that have indentations in their surface. Initially, this technology was mainly used to avoid and thus control the dose delivered to critical structures so that they are not seriously damaged in the process of irradiating nearby targets to an appropriately high dose. Avoidance of critical structures allowed homogeneous dose escalation that led to improved local control for small tumors. However, the normal tissue component of large tumors often prohibits homogeneous dose escalation. A newer concept of dose-painting IMRT is aimed at exploiting inhomogeneous dose distributions adapted to tumor heterogeneity. Tumor regions of increased radiation resistance receive escalated dose levels, whereas radiation-sensitive regions receive conventional or even de escalated dose levels. Dose painting relies on biologic imaging such as positron emission tomography, functional magnetic resonance imaging, and magnetic resonance spectroscopy. This review will describe the competing techologies for dose painting with an emphasis on their commonalities. PMID- 17350941 TI - Imaging and alignment for image-guided radiation therapy. AB - Image-guided radiation therapy is an exciting new area that focuses heavily on the potential benefit of advanced imaging and image registration to improve precision, thus limiting morbidity and potentially allowing for safe delivery of increased dose. This review explores the issues surrounding the use of imaging and image registration for treatment planning and verification, with emphasis on the underlying patient model and alignment algorithms. PMID- 17350942 TI - Advances in image-guided radiation therapy. AB - Imaging is central to radiation oncology practice, with advances in radiation oncology occurring in parallel to advances in imaging. Targets to be irradiated and normal tissues to be spared are delineated on computed tomography (CT) scans in the planning process. Computer-assisted design of the radiation dose distribution ensures that the objectives for target coverage and avoidance of healthy tissue are achieved. The radiation treatment units are now recognized as state-of-the-art robotics capable of three-dimensional soft tissue imaging immediately before, during, or after radiation delivery, improving the localization of the target at the time of radiation delivery, to ensure that radiation therapy is delivered as planned. Frequent imaging in the treatment room during a course of radiation therapy, with decisions made on the basis of imaging, is referred to as image-guided radiation therapy (IGRT). IGRT allows changes in tumor position, size, and shape to be measured during the course of therapy, with adjustments made to maximize the geometric accuracy and precision of radiation delivery, reducing the volume of healthy tissue irradiated and permitting dose escalation to the tumor. These geometric advantages increase the chance of tumor control, reduce the risk of toxicity after radiotherapy, and facilitate the development of shorter radiotherapy schedules. By reducing the variability in delivered doses across a population of patients, IGRT should also improve interpretation of future clinical trials. PMID- 17350943 TI - Stereotactic body radiation therapy in multiple organ sites. AB - INTRODUCTION: Stereotactic body radiation therapy (SBRT) uses advanced technology to deliver a potent ablative dose to deep-seated tumors in the lung, liver, spine, pancreas, kidney, and prostate. METHODS: SBRT involves constructing very compact high-dose volumes in and about the tumor. Tumor position must be accurately assessed throughout treatment, especially for tumors that move with respiration. Sophisticated image guidance and related treatment delivery technologies have developed to account for such motion and efficiently deliver high daily dose. All this serves to allow the delivery of ablative dose fractionation to the target capable of both disrupting tumor mitosis and cellular function. RESULTS: Prospective phase I dose-escalation trials have been carried out to reach potent tumoricidal dose levels capable of eradicating tumors with high likelihood. These studies indicate a clear dose-response relationship for tumor control with escalating dose of SBRT. Prospective phase II studies have been reported from several continents consistently showing very high levels of local tumor control. Although late toxicity requires further careful assessment, acute and subacute toxicities are generally acceptable. Patterns of toxicity, both clinical and radiographic, are distinct from those observed with conventionally fractionated radiotherapy as a result of the unique biologic response to ablative fractionation. CONCLUSION: Prospective trials using SBRT have confirmed the efficacy of treatment in a variety of patient populations. Although mechanisms of ablative-dose injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in the treatment arsenal. PMID- 17350944 TI - Particle radiation therapy using proton and heavier ion beams. AB - Particle beams like protons and heavier ions offer improved dose distributions compared with photon (also called x-ray) beams and thus enable dose escalation within the tumor while sparing normal tissues. Although protons have a biologic effectiveness comparable to photons, ions, because they are heavier than protons, provide a higher biologic effectiveness. Recent technologic developments in the fields of accelerator engineering, treatment planning, beam delivery, and tumor visualization have stimulated the process of transferring particle radiation therapy (RT) from physics laboratories to the clinic. This review describes the physical, biologic, and technologic aspects of particle beam therapy. Clinical trials investigating proton and carbon ion RT will be summarized and discussed in the context of their relevance to recent concepts of treatment with RT. PMID- 17350945 TI - Proton therapy in clinical practice: current clinical evidence. PMID- 17350946 TI - Intraoperative radiation therapy. AB - Intraoperative radiation therapy (IORT) is the delivery of irradiation at the time of an operation. This is performed by different techniques including intraoperative electron beam techniques and high-dose rate brachytherapy. IORT is usually given in combination with external-beam radiation therapy with or without chemotherapy and surgical resection. IORT excludes part or all dose-limiting sensitive structures, thereby increasing the effective dose to the tumor bed (and therefore local control) without significantly increasing normal tissue morbidity. Despite best contemporary therapy, high rates of local failure occur in patients with locally advanced or recurrent rectal cancer, retroperitoneal sarcoma, select gynecologic cancers, and other malignancies. The addition of IORT to conventional treatment methods has improved local control as well as survival in many disease sites in both the primary and locally recurrent disease settings. More recently, there has been interest in the use of IORT as a technique of partial breast irradiation for women with early breast cancer. Given newer and lower cost treatment devices, the use of IORT in clinical practice will likely grow, with increasing integration into the treatment of nonconventional malignancies. Optimally, phase III randomized trials will be carried out to prove its efficacy in these disease sites. PMID- 17350947 TI - Transcatheter and ablative therapeutic approaches for solid malignancies. AB - The purpose of this article is to present in a concise manner an overview of the most widely used locoregional transcatheter and ablative therapies for solid malignancies. An extensive MEDLINE search was performed for this review. Therapies used for liver cancer were emphasized because these therapies are used most commonly in the liver. Applications in pulmonary, renal, and bone tumors were also discussed. These approaches were divided into catheter-based therapies (such as transcatheter arterial chemoembolization, bland embolization, and the most recent transcatheter arterial approach with drug-eluting microspheres), ablative therapies (such as chemical [ethanol or acetic acid injection]), and thermal ablative therapies (such as radiofrequency ablation, laser induced thermotherapy, microwave ablation, cryoablation, and extracorporeal high intensity focused ultrasound ablation). A brief description of each technique and analysis of available data was reported for all therapies. Locoregional transcatheter and ablative therapies continue to be used mostly for palliation, but have also been used with curative intent. A growing body of evidence suggests clear survival benefit, excellent results regarding local tumor control, and improved quality of life. Clinical trials are underway to validate these results. Image-guided transcatheter and ablative approaches currently play an important role in the management of patients with various types of cancer-a role that is likely to grow even more given the technological advances in imaging, image guidance systems, catheters, ablative tools, and drug delivery systems. As a result, the outcomes of patients with cancer undoubtedly will improve. PMID- 17350948 TI - Advances in the treatment of localized prostate cancer: the role of anatomic and functional imaging in men managed with radiotherapy. AB - Radiation therapy is an active modality in the management of local and regional prostate cancer, but can be curative only if all existing disease is encompassed within the treatment portal. In addition to the ability to deliver sufficient radiation dose, accurate targeting is critical to achieve better treatment outcomes. Failure to accommodate daily variations in setup and organ motion potentially limits the efficacy of sophisticated conformal techniques (three dimensional conformal radiotherapy and intensity-modulated radiotherapy). Increased use of various online and real-time imaging techniques is an important step toward enhancing treatment accuracy. The incorporation of functional imaging techniques into treatment planning is another important step. The addition of biologic and metabolic information regarding the location and extent of disease combined with real-time online imaging will allow us to better determine where, how, and with what to treat appropriate targets and improve cure rates. PMID- 17350949 TI - Accelerated partial breast irradiation in early-stage breast cancer. AB - Whole-breast irradiation, as part of breast-conservation therapy (BCT), has well established results, good cosmesis, and low toxicity. Results from the BCT trials suggest that the risk for ipsilateral breast cancer recurrence resides within close proximity to the original tumor site. This leads investigators to consider the role of an accelerated and more tumor bed-focused course of radiotherapy. Accelerated partial-breast irradiation (APBI) involves treating a limited volume of breast tissue, with dose of irradiation per fraction increased and the treatment time course decreased. Four currently available methods of APBI are interstitial brachytherapy, intracavitary brachytherapy, intraoperative radiotherapy, and three-dimensional conformal external-beam radiotherapy. Patient selection is critical. This review article presents some preliminary clinical observations and limitations that suggest a potential role for APBI as a more user-friendly mode for delivering radiotherapy after lumpectomy for early breast cancer. PMID- 17350950 TI - Evidence-based recommendations for local therapy for soft tissue sarcomas. AB - There has been a gradual migration in the local treatment of soft tissue sarcomas from amputation and similar radical resectional approaches to more conservative, function-preserving surgery combined with radiotherapy. This progress has been made possible by small, single-institution, randomized trials that demonstrated the superiority of this more conservative, combined-modality approach. In the new millennium, attention has shifted to defining subsets of patients who might be adequately treated by surgery alone and defining the optimal sequence of surgery and radiation for patients who require both types of local therapy. There remains considerable discussion and debate surrounding the issue of pre- and postoperative chemotherapy for patients with localized soft tissue sarcomas. Adjuvant chemotherapy is a standard of care for adults who have the subtypes of soft tissue sarcomas that typically occur in pediatric patients (Ewing sarcoma, rhabdomyosarcoma), and just as clearly, adjuvant chemotherapy is not warranted in patients with low- and intermediate-risk disease (stages I and II). For patients with higher risk disease (stage III), the available randomized trials do not convincingly demonstrate a clinical benefit to adjuvant chemotherapy. As such, a complete accounting of potential risks and benefits is appropriate when discussing adjuvant chemotherapy with patients who have stage III disease. PMID- 17350951 TI - Future issues in highly conformal radiotherapy for head and neck cancer. AB - Improving the conformity of the radiation dose to targets in the head and neck promises reduced toxicity and, in some cases, potentially improved local-regional tumor control. Intensity-modulated radiotherapy (IMRT) is a method that allows highly conformal delivery of radiotherapy. In recent years, its use has spread rapidly in both academic and community radiation oncology facilities. The use of IMRT has raised multiple issues related to target definition, optimal treatment delivery methods, and the need to account for anatomic changes occurring during therapy. Some of these issues are reviewed in this article. PMID- 17350952 TI - Organ preservation for rectal cancer. AB - Organ preservation with maintenance of function in the treatment of rectal cancer is highly valued by patients. Although most patients with resectable rectal cancer can undergo a sphincter-sparing radical procedure, there are patient, tumor, surgeon, and treatment factors that influence the ability to restore intestinal continuity after radical resection. Although population-based data suggest that the rate of sphincter preservation is lower than could be obtained at expert centers, there are patients in whom low anterior resection with colo anal anastomosis is not technically feasible and/or oncologically sound. Additionally, resection with ultralow anastomosis results in functional compromise in many patients. Local treatment of rectal cancer aims to decrease the morbidity and the functional sequelae associated with radical resection; however, local excision is associated with a higher rate of local recurrence than is radical resection. Strict selection criteria are essential when considering local excision, and patients should be informed of the risk of local recurrence. The use of adjuvant therapy with local excision, particularly in patients with T2 lesions, has promise but should be considered only as part of a clinical trial. PMID- 17350953 TI - The rapamycin-binding domain of the protein kinase mammalian target of rapamycin is a destabilizing domain. AB - Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase. The resulting ternary complex has been used to conditionally perturb protein function, and one such method involves perturbation of a protein of interest through its mislocalization. We synthesized two rapamycin derivatives that possess large substituents at the C-16 position within the FRB-binding interface, and these derivatives were screened against a library of FRB mutants using a three-hybrid assay in Saccharomyces cerevisiae. Several FRB mutants responded to one of the rapamycin derivatives, and twenty of these mutants were further characterized in mammalian cells. The mutants most responsive to the ligand were fused to yellow fluorescent protein, and fluorescence levels in the presence and absence of the ligand were measured to determine stability of the fusion proteins. Wild-type and mutant FRB domains were expressed at low levels in the absence of the rapamycin derivative, and expression levels rose up to 10-fold upon treatment with ligand. The synthetic rapamycin derivatives were further analyzed using quantitative mass spectrometry, and one of the compounds was found to contain contaminating rapamycin. Furthermore, uncontaminated analogs retained the ability to inhibit mTOR, although with diminished potency relative to rapamycin. The ligand-dependent stability displayed by wild-type FRB and FRB mutants as well as the inhibitory potential and purity of the rapamycin derivatives should be considered as potentially confounding experimental variables when using these systems. PMID- 17350954 TI - Regulation of ionizing radiation-induced apoptosis by mitochondrial NADP+ dependent isocitrate dehydrogenase. AB - Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. By supplying NADPH for antioxidant systems, we recently demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage are some of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm). In this study, we demonstrate that modulation of IDPm activity in U937 cells regulates ionizing radiation-induced apoptosis. When we examined the regulatory role of IDPm against ionizing radiation-induced apoptosis in U937 cells transfected with the cDNA for mouse IDPm in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPm expressed in target cells and their susceptibility to apoptosis. Upon exposure to 2 gray gamma-irradiation, there was a distinct difference between the IDPm transfectant cells in regard to the morphological evidence of apoptosis, DNA fragmentation, cellular redox status, oxidative damage to cells, mitochondrial function, and the modulation of apoptotic marker proteins. In addition, transfection of HeLa cells with an IDPm small interfering RNA decreased the activity of IDPm, enhancing the susceptibility of radiation-induced apoptosis. Taken together, these results indicate that IDPm may play an important role in regulating the apoptosis induced by ionizing radiation, and the effect of IDPm small interfering RNA on HeLa cells offers the possibility of developing a modifier of radiation therapy. PMID- 17350955 TI - Characterization of the Pseudomonas aeruginosa Lol system as a lipoprotein sorting mechanism. AB - Escherichia coli lipoproteins are localized to either the inner or the outer membrane depending on the residue that is present next to the N-terminal acylated Cys. Asp at position 2 causes the retention of lipoproteins in the inner membrane. In contrast, the accompanying study (9) revealed that the residues at positions 3 and 4 determine the membrane specificity of lipoproteins in Pseudomonas aeruginosa. Since the five Lol proteins involved in the sorting of E. coli lipoproteins are conserved in P. aeruginosa, we examined whether or not the Lol proteins of P. aeruginosa are also involved in lipoprotein sorting but utilize different signals. The genes encoding LolCDE, LolA, and LolB homologues were cloned and expressed. The LolCDE homologue thus purified was reconstituted into proteoliposomes with lipoproteins. When incubated in the presence of ATP and a LolA homologue, the reconstituted LolCDE homologue released lipoproteins, leading to the formation of a LolA-lipoprotein complex. Lipoproteins were then incorporated into the outer membrane depending on a LolB homologue. As revealed in vivo, lipoproteins with Lys and Ser at positions 3 and 4, respectively, remained in proteoliposomes. On the other hand, E. coli LolCDE released lipoproteins with this signal and transferred them to LolA of not only E. coli but also P. aeruginosa. These results indicate that Lol proteins are responsible for the sorting of lipoproteins to the outer membrane of P. aeruginosa, as in the case of E. coli, but respond differently to inner membrane retention signals. PMID- 17350956 TI - Amino acids at positions 3 and 4 determine the membrane specificity of Pseudomonas aeruginosa lipoproteins. AB - Escherichia coli lipoproteins with Asp at position 2 remain in the inner membrane, whereas those having other amino acids are targeted to the outer membrane by the Lol system. However, inner membrane lipoproteins without Asp at position 2 are found in other Gram-negative bacteria. MexA of Pseudomonas aeruginosa, an inner membrane-specific lipoprotein involved in multidrug efflux, has Gly at position 2. To identify the residue or region of MexA that functions as an inner membrane retention signal, we constructed chimeric lipoproteins comprising various regions of MexA and an outer membrane lipoprotein, OprM, and analyzed their membrane localization. Lys and Ser at positions 3 and 4, respectively, were found to be critical for the inner membrane localization of MexA in P. aeruginosa. Substitution of these residues with Leu and Ile, which are present in OprM, was sufficient to target the chimeric lipoprotein to the outer membrane and to abolish the ability of MexA to confer drug resistance. The membrane specificity of a model lipoprotein, lipoMalE, a lipidated variant of the periplasmic maltose-binding protein of E. coli, was also determined by the residues at positions 3 and 4 in P. aeruginosa. In contrast to the widely accepted "+2 rule" for E. coli lipoproteins, these results suggest a new "+3, +4 rule" for lipoprotein sorting in P. aeruginosa, namely, the final destination of lipoproteins is determined by the residues at positions 3 and 4. PMID- 17350957 TI - Dual role for SUMO E2 conjugase Ubc9 in modulating the transforming and growth promoting properties of the HMGA1b architectural transcription factor. AB - Members of the HMGA1 (high mobility group A1) family of architectural transcription factors, HMGA1a and HMGA1b, play important roles in many normal cellular processes and in tumorigenesis. We performed a yeast two-hybrid screen for HMGA1-interacting proteins and identified the SUMO E2 conjugase Ubc9 as one such partner. The Ubc9-interacting domain of HMGA1 is bipartite, consisting of a proline-rich region near the N terminus and an acidic domain at the extreme C terminus, whereas the HMGA1-interacting domain of Ubc9 comprises a single region previously shown to associate with and SUMOylate other transcription factors. Consistent with these findings, endogenous HMGA1 proteins and Ubc9 could be co immunoprecipitated from several human cell lines. Studies with HMGA1b proteins containing mutations of either or both Ubc9-interacting domains and with Ubc9 depleted cell lines indicated that the proline-rich domain of HMGA1b positively influences transformation and growth, whereas the acidic domain negatively influences these properties. None of the changes in HMGA1 protein functions mediated by Ubc9 appears to require SUMOylation. These findings are consistent with the idea that Ubc9 can act as both a positive and negative regulator of proliferation and transformation via its non-SUMO-dependent interaction with HMGA1 proteins. PMID- 17350958 TI - SufE transfers sulfur from SufS to SufB for iron-sulfur cluster assembly. AB - Iron-sulfur (Fe-S) clusters are key metal cofactors of metabolic, regulatory, and stress response proteins in most organisms. The unique properties of these clusters make them susceptible to disruption by iron starvation or oxidative stress. Both iron and sulfur can be perturbed under stress conditions, leading to Fe-S cluster defects. Bacteria and higher plants contain a specialized system for Fe-S cluster biosynthesis under stress, namely the Suf pathway. In Escherichia coli the Suf pathway consists of six proteins with functions that are only partially characterized. Here we describe how the SufS and SufE proteins interact with the SufBCD protein complex to facilitate sulfur liberation from cysteine and donation for Fe-S cluster assembly. It was previously shown that the cysteine desulfurase SufS donates sulfur to the sulfur transfer protein SufE. We have found here that SufE in turn interacts with the SufB protein for sulfur transfer to that protein. The interaction occurs only if SufC is present. Furthermore, SufB can act as a site for Fe-S cluster assembly in the Suf system. This provides the first evidence of a novel site for Fe-S cluster assembly in the SufBCD complex. PMID- 17350959 TI - Ground state structure of F1-ATPase from bovine heart mitochondria at 1.9 A resolution. AB - The structure of bovine F(1)-ATPase, crystallized in the presence of AMP-PNP and ADP, but in the absence of azide, has been determined at 1.9A resolution. This structure has been compared with the previously described structure of bovine F(1)-ATPase determined at 1.95A resolution with crystals grown under the same conditions but in the presence of azide. The two structures are extremely similar, but they differ in the nucleotides that are bound to the catalytic site in the beta(DP)-subunit. In the present structure, the nucleotide binding sites in the beta(DP)- and beta(TP)-subunits are both occupied by AMP-PNP, whereas in the earlier structure, the beta(TP) site was occupied by AMP-PNP and the beta(DP) site by ADP, where its binding is enhanced by a bound azide ion. Also, the conformation of the side chain of the catalytically important residue, alphaArg 373 differs in the beta(DP)- and beta(TP)-subunits. Thus, the structure with bound azide represents the ADP inhibited state of the enzyme, and the new structure represents a ground state intermediate in the active catalytic cycle of ATP hydrolysis. PMID- 17350961 TI - The effect of the readthrough acetylcholinesterase variant (AChE-R) on uterine muscle and leiomyomas. AB - Acetylcholine signaling and acetylcholinesterase (AChE) function(s) are pivotal elements in muscle development. The effects of the stimulus-dependent readthrough AChE variant, AChE-R, on leiomyomas and normal myometrium proliferation were assessed in vivo and in vitro. Histological preparations and cell cultures therefrom were obtained during hysterectomies or myomectomies and included both the leiomyoma sample and the adjacent normal uterine muscle as control. In situ hybridization procedures were performed using AChE cRNA probes complementary to the human AChE-R transcript. Antibodies against the AChE-R variant served for immunohistochemical staining. To determine the biological function of AChE-R on the uterine muscle cell cultures, we used a synthetic peptide representing the potentially cleavable morphogenically active C-terminus of AChE-R (ARP). Cell proliferation was assessed using the incorporation of 5'-bromo-2-deoxyuridine (BrDU). Leiomyomas expressed an excess of AChE-R mRNA and the AChE-R protein compared with the normal myometrium. Cell cultures originating from leiomyomas proliferated significantly faster than cultures from the adjacent myometrium (P = 0.027 at BrDU incorporation). Addition of ARP (2-200 nM) caused a dose-dependent decrease in the proliferation of cell cultures from both leiomyomas and the myometrium. The effect on the myometrium reached statistical significance (at 20 and 200 nM, P = 0.02), whereas the variability of the rapidly proliferating primary cultures was high and precluded statistical significance in the leiomyoma cultures. AChE-R is involved in the proliferation of the myometrium. The inhibitory effect of ARP on the myometrium may suggest a future therapeutic role of ARP. PMID- 17350960 TI - Protein kinase C delta is required for survival of cells expressing activated p21RAS. AB - Inhibition of protein kinase C (PKC) activity in transformed cells and tumor cells containing activated p21(RAS) results in apoptosis. To investigate the pro apoptotic pathway induced by the p21(RAS) oncoprotein, we first identified the specific PKC isozyme necessary to prevent apoptosis in the presence of activated p21(RAS). Dominant-negative mutants of PKC, short interfering RNA vectors, and PKC isozyme-specific chemical inhibitors directed against the PKCdelta isozyme demonstrated that PKCdelta plays a critical role in p21(RAS)-mediated apoptosis. An activating p21(RAS) mutation, or activation of the phosphatidylinositol 3 kinase (PI3K) Ras effector pathway, increased the levels of PKCdelta protein and activity in cells, whereas inhibition of p21(RAS) activity decreased the expression of the PKCdelta protein. Activation of the Akt survival pathway by oncogenic Ras required PKCdelta activity. Akt activity was dramatically decreased after PKCdelta suppression in cells containing activated p21(RAS). Conversely, constitutively activated Akt rescued cells from apoptosis induced by PKCdelta inhibition. Collectively, these findings demonstrate that p21(RAS), through its downstream effector PI3K, induces PKCdelta expression and that this increase in PKCdelta activity, acting through Akt, is required for cell survival. The p21(RAS) effector molecule responsible for the initiation of the apoptotic signal after suppression of PKCdelta activity was also determined to be PI3K. PI3K (p110(C)(AAX), where AA is aliphatic amino acid) was sufficient for induction of apoptosis after PKCdelta inhibition. Thus, the same p21(RAS) effector, PI3K, is responsible for delivering both a pro-apoptotic signal and a survival signal, the latter being mediated by PKCdelta and Akt. Selective suppression of PKCdelta activity and consequent induction of apoptosis is a potential strategy for targeting of tumor cells containing an activated p21(RAS). PMID- 17350962 TI - Normalization of hormonal imbalances, ovarian follicular dynamics and metabolic effects in follitrophin receptor knockout mice. AB - Genetically modified follitrophin receptor knockout female mice with total FSH receptor (FSH-R) deletion are sterile and their combined estrogen deficiency hyperandrogenemic status provides an experimental paradigm to study the effect of hormonal imbalances on ovarian function and metabolic alterations. Elevated LH levels causing hyperandrogenemia perturb normal folliculogenesis. To control diverse pathophysiology associated with hormonal imbalances, we investigated the effects of transplanting a single normal mouse ovary in young mutants. An intact FSH-R signalling system in the graft responded promptly to the up-regulated pituitary gonadotrophins circulating in the host mutant. Resumption of regular estrous cycles validated stimulation of uterine functions. Secretions from the viable functioning grafts partially corrected follicular abnormalities originally present in host ovaries. Stromal hyperplasia responsible for high ovarian LH receptor and key enzymes in host thecal/interstitial complex and hyperandrogenemia was reduced in host ovaries. Increases in plasma estradiol and reduced LH and free testosterone re-established the negative-feedback system. Reduced android obesity and activation of mammary glands indicated the combined beneficial effects of normalized steroid hormones on target organs. These data provide evidence that ovarian transplantation in mutants corrects estrogen loss and hyperandrogenemia. However, correction of hormonal imbalances is not sufficient to fully restore effects of FSH-R loss in host granulosa cells. PMID- 17350963 TI - Altered expression of HOXA10 in endometriosis: potential role in decidualization. AB - Endometriosis is a poorly understood gynaecologic disorder that is associated with infertility. In this study, we examined the expression of HOXA10 in the eutopic endometrium of baboons with induced endometriosis. A decrease in HOXA10 mRNA was observed after 3, 6, 12 and 16 months of disease, which reached statistical significance at 12 and 16 months. HOXA10 protein levels were decreased in both the epithelial and stromal cells of the endometrium. Furthermore, expression of beta3 integrin (ITGB3), which is upregulated by HOXA10, was decreased, whereas EMX2, a gene that is inhibited by HOXA10, was increased. Next, methylation patterns of the HOXA10 gene were analysed in the diseased and control animals. The F1 region on the promoter was found to be the most significantly methylated in the endometriosis animals and this may account for the decrease in HOXA10 expression. Finally, we demonstrate that stromal cells from the eutopic endometrium of baboons with endometriosis expressed significantly higher levels of insulin-like growth factor binding protein-1 (IGFBP1) mRNA than disease-free animals in response to estradiol, medroxyprogesterone acetate and dibutyryl cAMP (H + dbcAMP). The functional role of HOXA10 in IGFBP1 expression was further explored using human endometrial stromal cells (HSC). Overexpression of HOXA10 in HSC resulted in a decrease of IGFBP1 mRNA, whereas silencing HOXA10 caused an increase of IGFBP1 mRNA, even in the presence of H + dbcAMP. These data demonstrate that HOXA10 negatively influences IGFBP1 expression in decidualizing cells. Thus, the decrease in HOXA10 levels may in part be involved with the altered uterine environment associated with endometriosis. PMID- 17350964 TI - PI3K/Akt and ERK1/2 signalling pathways are involved in endometrial cell migration induced by 17beta-estradiol and growth factors. AB - Cell motility and invasion are crucial events for endometrial cells, not only for the establishment of pathological states but also during the physiological tissue remodelling that occurs during the menstrual cycle and embryo implantation. We have characterized these phenomena in endometrial stromal cells evaluating cell migration-specific stimuli and the biochemical pathways involved. Ability of endometrial cells to migrate on collagen type IV substrate was evaluated by means of chemotaxis experiments. Modulation of this phenomenon by different growth factors and steroid hormones and their ability to activate extracellular signal regulated protein kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/Akt signalling in this context were examined. Platelet-derived growth factor (PDGF) BB, epidermal growth factor and fibroblast growth factor-2 as chemoattractant agents stimulated basal migration of endometrial stromal cells through the rapid activation of both ERK1/2 and PI3K/Akt signalling pathways. Experiments using wortmannin and PD98059, specific inhibitors of the PI3K/Akt and ERK1/2 activity, respectively, showed that the activation of both pathways is required for growth factor-induced cell motility responses. Similarly, 17beta-estradiol (10(-6)-10( 8) M) could enhance both constitutive and PDGF-induced migration of the cells and their rapid treatment with the hormone significantly increased phosphorylation of ERK1/2 and Akt. Conversely, progesterone did not interfere with the basal migration but inhibits the PDGF-induced motility of this cell type. Rapid activation of intracellular signalling cascades ERK1/2 and PI3K/Akt by growth factors and estrogens is involved in the migration of normal endometrial stromal cells. PMID- 17350965 TI - Parenting programme for parents of children at risk of developing conduct disorder: cost effectiveness analysis. AB - OBJECTIVE: To investigate the cost effectiveness of a parenting programme. DESIGN: An incremental cost effectiveness analysis alongside a pragmatic randomised controlled trial of the effectiveness of a group parenting programme delivered through Sure Start in the community. SETTING: Sure Start areas in north and mid Wales. PARTICIPANTS: Parents of 116 children aged 36-59 months (87% of the clinical sample) at risk of developing conduct disorders defined by scoring over the clinical cut off on the Eyberg child behaviour inventory). Children were identified by health visitors and recruited by the research team. INTERVENTION: The Webster-Stratton Incredible Years basic parenting programme or a six month waiting list control. MAIN OUTCOME MEASURE: Incremental cost per unit of improvement on the intensity score of the Eyberg child behaviour inventory. RESULTS: The bootstrapped incremental cost effectiveness ratio point estimate was 73 pounds sterling (109 euros, $142) per one point improvement on the intensity score (95% confidence interval 42 pounds sterling to 140 pounds sterling ). It would cost 5486 (8190 euros, $10,666) to bring the child with the highest intensity score to below the clinical cut-off point and 1344 (2006 euros, $2618) to bring the average child in the intervention group within the non-clinical limits on the intensity score (below 127). For a ceiling ratio of 100 pounds sterling (149 euros, $194) per point increase in intensity score, there is an 83.9% chance of the intervention being cost effective. The mean cost per child attending the parenting group was 1934 pounds sterling (2887 euros, $3760) for eight children and 1289 pounds sterling (1924 euros, $2506) for 12 children, including initial costs and materials for training group leaders. When we categorised the sample into relatively mild, moderate, and severe behaviour groups based on intensity scores at baseline the intervention seemed more cost effective in those with the highest risk of developing conduct disorder. CONCLUSION: This parenting programme improves child behaviour as measured by the intensity score of the Eyberg child behaviour inventory at a relatively low cost and was cost effective compared with the waiting list control. This parenting programme involves modest costs and demonstrates strong clinical effect, suggesting it would represent good value for money for public spending. PMID- 17350966 TI - Parenting intervention in Sure Start services for children at risk of developing conduct disorder: pragmatic randomised controlled trial. AB - OBJECTIVE: To evaluate the effectiveness of a parenting programme as a preventive intervention with parents of preschool children considered to be at risk of developing conduct disorder. DESIGN: Pragmatic randomised controlled trial using a block design with allocation by area. SETTING: Eleven Sure Start areas in north and mid-Wales. PARTICIPANTS: 153 parents from socially disadvantaged areas, with children aged 36-59 months at risk of conduct disorder defined by scoring over the clinical cut off on the Eyberg child behaviour inventory. Participants were randomised on a 2:1 basis, 104 to intervention and 49 to remaining on the wait listing (control). Twenty (13%) were lost to follow-up six months later, 18 from the intervention group. INTERVENTION: The Webster-Stratton Incredible Years basic parenting programme, a 12 week group based intervention. MAIN OUTCOME MEASURES: Problem behaviour in children and parenting skills assessed by self reports from parents and by direct observation in the home. Parents' self reported parenting competence, stress, and depression. Standardised and well validated instruments were used throughout. RESULTS: At follow-up, most of the measures of parenting and problem behaviour in children showed significant improvement in the intervention group. The intention to treat analysis for the primary outcome measure, the Eyberg child behaviour inventory, showed a mean difference between groups of 4.4 points (95% confidence interval 2.0 to 6.9, P<0.001) on the problem scale with an effect size of 0.63, and a mean difference of 25.1 (14.9 to 35.2, P<0.001) on the intensity scale with an effect size of 0.89. CONCLUSION: This community based study showed the effectiveness of an evidence based parenting intervention delivered with fidelity by regular Sure Start staff. It has influenced policy within Wales and provides lessons for England where, to date, Sure Start programmes have not been effective. TRIAL REGISTRATION: ISRCTN46984318. PMID- 17350967 TI - Impact of NHS walk-in centres on primary care access times: ecological study. AB - OBJECTIVE: To examine whether walk-in centres contribute to shorter waiting times for a general practice appointment. DESIGN: Ecological study. SETTING: 2509 general practices in 56 primary care trusts in England; 32 walk-in centres within 3 km of one of these practices. MAIN OUTCOME MEASURE: Waiting time to next available general practitioner appointment (April 2003 to December 2004), from national monthly primary care access survey. RESULTS: The percentage of practices achieving the target waiting time of less than 48 hours to see a general practitioner increased from 67% to 87% over the 21 month study period (adjusted odds ratio 1.07 (95% confidence interval 1.06 to 1.08) per increase in month). Achievement of the waiting time target decreased with increasing multiple deprivation (0.57 (0.49 to 0.67) for most versus least deprived third) and increased with increasing practice population size (1.02 (1.00 to 1.04) per 1000 increase). No evidence was found that increasing distance from a walk-in centre was associated with decreasing odds of achieving the waiting time target (1.00 (0.99 to 1.01) per km increase). Increasing "exposure" to a walk-in centre, modelled with a distance decay function based on attendance rates, also showed little evidence of association with achievement of the waiting time target (1.02 (0.97 to 1.08) for interquartile range increase). No evidence existed that the rate of increase in achieving the 48 hour target over time was enhanced by proximity or "exposure" to a walk-in centre. Results were similar when the analysis was rerun with data for 2003 only (done because pressure in 2004 to meet the government's deadline might have led to other changes that could have masked any walk-in centre effect). CONCLUSIONS: No evidence existed that walk-in centres shortened waiting times for access to primary care, and the results do not support the use of walk-in centres for this purpose. PMID- 17350968 TI - Circulating levels of the chemokine CCL18 but not CXCL16 are elevated and correlate with disease activity in rheumatoid arthritis. AB - BACKGROUND: Antigen-presenting cells (APC) and T cells are considered to play a significant role in the pathogenesis of rheumatoid arthritis (RA). CCL18 and CXCL16 are two chemokines that facilitate T cell attraction by APC, of which a role in the pathogenesis of RA has been suggested. OBJECTIVE: To compare the circulating levels of CXCL16 and CCL18 in RA with controls and to investigate the relation of CXCL16 and CCL18 with RA disease activity and joint damage. METHODS: Circulating CCL18 and CXCL16 levels were determined in 61 RA patients with a follow-up of 6 years and a group of 41 healthy controls with ELISA. Chemokine levels were correlated with demographic data, disease activity (DAS28) and joint damage (modified Sharp score). In addition, serum CCL18 and CXCL16 levels from a cohort of 44 RA patients treated with anti-TNF-alpha were correlated with disease activity. RESULTS: CCL18 levels in serum were significantly elevated in RA patients compared with controls, while serum CXCL16 levels were not. In contrast to CXCL16, serum CCL18 was positively correlated with disease activity. Both CCL18 and CXCL16 levels decreased upon treatment with anti-TNF-alpha. Neither CCL18 nor CXCL16 correlated with joint damage and progression. CONCLUSION: Here, we show, for the first time, that circulating CCL18 and not CXCL16 levels are elevated in RA patients as compared with controls and correlate with disease activity in RA. More knowledge regarding the regulation and function of both CCL18 and CXCL16 is essential to value their role in RA. PMID- 17350969 TI - Surgical stress index reflects surgical stress in gynaecological laparoscopic day case surgery. AB - BACKGROUND: Monitoring of analgesia remains a challenge during general anaesthesia. The surgical stress index (SSI) is derived from the photoplethysmographic waveform amplitude and the heart beat-to-beat interval. We evaluated the ability of SSI to measure surgical stress in patients undergoing gynaecological laparoscopy. Our hypothesis was that while keeping State Entropy (SE) at a predetermined level, SSI would be higher in patients receiving a beta blocking agent (esmolol) than in those receiving an opioid (remifentanil) during laparoscopy. METHODS: Thirty women undergoing gynaecological laparoscopy were assigned randomly to receive esmolol (n = 15) or remifentanil (n = 15). Anaesthesia was induced with propofol and fentanyl and maintained with desflurane and nitrous oxide 50% in oxygen to keep SE at 50(5). The infusion of esmolol or remifentanil was started before laparoscopy and adjusted to keep the systolic blood pressure at -20 to +10% from the preoperative value. RESULTS: During the fentanyl phase, before surgery, both groups behaved similarly, with an increase in SSI after intubation. In the patients receiving esmolol, the SSI reacted to the initial incision (P < 0.05), and remained high after trocar insertion (P < 0.05). In patients receiving remifentanil, it did not react to the initial incision, but increased after trocar insertion (P < 0.05), and it remained lower both after incision (P < 0.05) and after trocar insertion (P < 0.05). CONCLUSION: SSI was higher in patients receiving esmolol. The index seems to reflect the level of surgical stress and may help guide the use of opioids during general anaesthesia. PMID- 17350970 TI - Potential effect of NICE tuberculosis guidelines on paediatric tuberculosis screening. AB - OBJECTIVE: Assays based on interferon gamma (IFNgamma) are an exciting new development for screening for latent tuberculosis infection (LTBI) in adults, but there are limited data on their effectiveness in children. Nevertheless new National Institute for Health and Clinical Excellence (NICE) guidelines recommend their use when screening paediatric tuberculosis (TB) contacts. We evaluated the potential effect of the new NICE guidelines on current paediatric practice. DESIGN: Children screened for TB who had had an IFNgamma assay performed (QuantiFERON-TB Gold (QFG)) were included. Actual outcomes from existing guidelines were compared with those that would have been obtained using NICE guidelines. RESULTS: QFG assays were performed on 120 children, 103 as part of TB contact tracing. Six of the 120 (5%) were QFG positive, and seven of the 120 (6%) were indeterminate. Where both Mantoux and QFG results were available, these agreed in 62/104 (60%) of cases. QFG tests were more likely to correlate with a negative Mantoux (98% agreement) than with a positive Mantoux (11% agreement). Management outcomes differed for 23/103 children seen as part of TB contact tracing. Only one (1%) of these had an indeterminate QFG result. 17 (85%) fewer children would have been given LTBI treatment (chemoprophylaxis) and two (2%) children with possible TB would not have been identified using NICE guidelines. CONCLUSION: New NICE guidelines for the use of IFNgamma-based tests for TB screening will reduce the number of children treated for presumed LTBI. Long-term prospective studies are needed to determine the number of children with positive Mantoux tests but negative IFNgamma results who are not given LTBI treatment yet later develop TB. PMID- 17350971 TI - What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery? AB - AIM: To identify the proportion and characteristics of patients with severe symptomatic mitral regurgitation (MR) who are denied surgery. METHODS AND RESULTS: In the Euro Heart Survey on valvular heart disease, 396 patients had severe symptomatic MR as assessed by Doppler-echocardiography (grade > or =3/4) and New York Heart Association class II or greater. Patient characteristics were analysed according to the decision to operate or not. A decision not to operate was taken in 193 patients (49%). In multivariable analysis, decreased left ventricular ejection fraction (LVEF) [OR = 1.39 per 10% decrease, 95% CI (1.17 1.66), P = 0.0002], non-ischaemic aetiology [OR = 4.44, 95% CI (1.96-10.76), P = 0.0006], older age [OR = 1.40 per 10-year increase, 95% CI (1.15-1.72), P = 0.001], increased Charlson comorbidity index [OR = 1.38 per 1 point increase, 95% CI (1.12-1.72), P = 0.004], and grade 3 MR [OR = 2.23, 95% CI (1.28-3.29), P = 0.005] were associated with the decision not to operate. One-year survival was 96.0 +/- 1.4% in patients with a positive decision for intervention vs. 89.5 +/- 2.3% in those with a negative decision (P = 0.02). CONCLUSION: Surgery was denied in 49% of patients with severe symptomatic MR. Impaired LVEF, older age, and comorbidity were the most striking characteristics of patients who were denied surgery. The weight of age and LVEF in the decision do not seem justified according to current knowledge. PMID- 17350973 TI - Discovery of microRNA-mRNA modules via population-based probabilistic learning. AB - MOTIVATION: MicroRNAs (miRNAs) and mRNAs constitute an important part of gene regulatory networks, influencing diverse biological phenomena. Elucidating closely related miRNAs and mRNAs can be an essential first step towards the discovery of their combinatorial effects on different cellular states. Here, we propose a probabilistic learning method to identify synergistic miRNAs involving regulation of their condition-specific target genes (mRNAs) from multiple information sources, i.e. computationally predicted target genes of miRNAs and their respective expression profiles. RESULTS: We used data sets consisting of miRNA-target gene binding information and expression profiles of miRNAs and mRNAs on human cancer samples. Our method allowed us to detect functionally correlated miRNA-mRNA modules involved in specific biological processes from multiple data sources by using a balanced fitness function and efficient searching over multiple populations. The proposed algorithm found two miRNA-mRNA modules, highly correlated with respect to their expression and biological function. Moreover, the mRNAs included in the same module showed much higher correlations when the related miRNAs were highly expressed, demonstrating our method's ability for finding coherent miRNA-mRNA modules. Most members of these modules have been reported to be closely related with cancer. Consequently, our method can provide a primary source of miRNA and target sets presumed to constitute closely related parts of gene regulatory pathways. PMID- 17350972 TI - Adjunctive value of CT coronary angiography in the diagnostic work-up of patients with typical angina pectoris. AB - AIMS: To determine the adjunctive value of CT coronary angiography (CTCA) in the diagnostic work-up of patients with typical angina pectoris. METHODS AND RESULTS: CTCA was performed in 62 consecutive patients (45 male, mean age 58.8 +/- 7.7 years) with typical angina undergoing diagnostic work-up including exercise-ECG and conventional coronary angiography. Only patients with sinus heart rhythm and ability to breath hold for 20 s were included. Patients with initial heart rates >/=70 beats/min received beta-blockers. We determined the post-test likelihood ratios, to detect or exclude patients with significant (>/=50% lumen diameter reduction) stenoses, of exercise-ECG and CTCA separately, and of CT performed after exercise-ECG testing. The prevalence of patients with significant coronary artery disease (CAD) was 74%. Positive and negative likelihood ratios for exercise-ECG were 2.3 [95% confidence interval (CI): 1.0-5.3] and 0.3 (95% CI: 0.2-0.7) and for CTCA 7.5 (95% CI: 2.1-27.1) and 0.0 (95% CI: 0.0-8), respectively. CTCA increased the post-test probability of significant CAD after a negative exercise-ECG from 58 to 91%, and after a positive exercise-ECG from 89 to 99%, while CT correctly identified patients without CAD (probability 0%). CONCLUSION: Non-invasive CTCA is a potentially useful tool, in the diagnostic work-up of patients with typical angina pectoris, both to detect and to exclude significant CAD. PMID- 17350974 TI - 'Faster counting while walking' as a predictor of falls in older adults. AB - OBJECTIVE: To establish whether changes in a spoken verbal task performance while walking compared with being at rest could predict falls among older adults. DESIGN: Prospective cohort study of 12 months' duration. SETTING: Twenty-seven senior housing facilities. PARTICIPANTS: Sample of 187 subjects aged 75-100 (mean age 84.8 +/- 5.2). During enrollment, participants were asked to count aloud backward from 50, both at rest and while walking and were divided into two groups according to their counting performance. Information on incident falls during the follow-up year was monthly collected. MEASUREMENTS: The number of enumerated figures while sitting on a chair and while walking, and the first fall that occurred during the follow up year. RESULTS: The number of enumerated figures under dual-task as compared to single task increased among 31.5% of the tested subjects (n = 59) and was associated with lower scores in MMSE (P = 0.034), and higher scores in Geriatric Depression Scale (P = 0.007) and Timed Up & Go (P = 0.005). During the 12 months follow-up, 54 subjects (28.9%) fell. After adjusting for these variables, the increase in counting performance was significantly associated with falls (adjusted OR = 53.3, P < 0.0001). Kaplan-Meier distributions of falls differed significantly between subjects who either increased or decreased their counting performance (P < 0.0001). CONCLUSIONS: Faster counting while walking was strongly associated with falls, suggesting that better performance in an additional verbal counting task while walking might represent a new way to predict falls among older adults. PMID- 17350975 TI - Cholinesterase inhibitors and cardiovascular disease: a survey of old age psychiatrists' practice. PMID- 17350976 TI - Cognitive impairment and MRI correlates in the elderly patients with type 2 diabetes mellitus. AB - BACKGROUND: exact mechanisms underlying cognitive dysfunction in diabetes mellitus (DM) remain unclear. Imaging studies of the brain could help to identify possible structural brain lesions underlying cognitive dysfunction. OBJECTIVE: to describe a detailed neuropsychological profile in patients functioning independently with type 2 DM. Secondly, correlations were studied between cognitive impairment and brain lesions on magnetic resonance imaging (MRI), i.e. periventricular hyperintensities (PVH), deep white matter lesions (DWML), medial temporal lobe atrophy (MTA), cerebral atrophy and lacunar infarcts. In addition, the influence of relevant disease variables of DM was studied. METHODS: 92 patients with type 2 DM (mean age 73.2 +/- 5.7 years, mean duration 13.8 +/- 10.8 years) and 44 control subjects (mean age 72.9 +/- 5.3 years) were included and underwent an extensive neuropsychological test battery and an MRI of the brain. RESULTS: neuropsychological scores were worse for each cognitive domain except for memory functions after adjustment for hypertension in a group of elderly patients with type 2 DM compared to healthy control subjects. Only PVH were independently associated with motor speed, whereas all other MRI measures were not independently associated with cognitive impairment. Interactions between the different MRI measures were not present. Glycosylated haemoglobin (HbA(1c)) and duration of DM were significantly associated with cognitive dysfunction. CONCLUSIONS: the data of this cross-sectional study show that type 2 DM is associated with diminished cognitive function in different cognitive domains, while memory is less affected after adjustment for hypertension. The association of cognitive impairment with MRI measures is equivocal, whereas HbA(1c) and duration of DM were significantly associated with cognitive dysfunction. PMID- 17350977 TI - Type of alcohol consumed, changes in intake over time and mortality: the Leisure World Cohort Study. AB - BACKGROUND: modifiable behavioural risk factors including smoking and alcohol consumption are major contributing or actual causes of mortality. OBJECTIVE: to examine the effect of alcohol intake on all-cause mortality in older adults. DESIGN AND SETTING: prospective population-based cohort study of residents of a California, United States retirement community. SUBJECTS: 8,877 women and 5,101 men (median age, 74 years) who in the early 1980s completed a postal health srvey incluing details on alcohol consumption. METHODS: participants were followed for 23 years (1981-2004) including two follow-up questionnaires (in 1992 and 1998) asking about current alcohol intake. Age-adjusted and multivariate-adjusted risk ratios of death and 95% confidence intervals were calculated separately for men and women, using proportional hazard regression. RESULTS: of the 8,644 women and 4,980 men with complete information on the variables of interest and potential confounders, 6,930 women and 4,456 men had died (median age, 87 years). Both men and women who drank alcohol had decreased mortality compared with non-drinkers. Those who drank two or more drinks per day had a 15% reduced risk of death. The reduced risk was not limited to one type of alcohol. Stable drinkers (those who reported drinking both at baseline and follow-up) had a significantly decreased risk of death compared with stable non-drinkers. Those who started drinking at follow-up also had a significantly lower risk. Women who quit drinking were at increased risk of death. CONCLUSION: in elderly men and women, moderate alcohol intake exhibits a beneficial effect on mortality. Those who quit may do so for health reasons that affect mortality. PMID- 17350979 TI - MTHFR C677T has differential influence on risk of MSI and MSS colorectal cancer. AB - The majority of colorectal cancer (CRC) exhibiting the micosatellite instability (MSI) phenotype is due to hypermethylation of the hMLH1 gene promoter. We aimed to test the hypothesis that polymorphisms in genes coding for enzymes involved in folate metabolism play a role in altered promoter-specific hypermethylation and thus predispose to MSI CRC. Analysis of MSI was performed in 1685 CRCs, and polymorphism genotypes were determined in germline DNA for all cases and 2692 cancer-free controls. MSI was observed in 171 cancers (10.1%). Compared to homozygous wild-type individuals, those with MTHFR 677TT genotype were more likely to have MSI than microsatellite stable (MSS) CRC [odds ratio (OR) 1.90; 95% confidence interval (CI): 1.09-3.31]. When MTHFR C677T genotype frequencies in MSS CRC cases were compared to controls, individuals with homozygous variant genotype were at 19% reduced risk of cancer compared to wild type (OR = 0.81; 95% CI: 0.65-1.02). Conversely, when MSI CRC cases were compared to controls, individuals with one or two MTHFR 677T alleles were at 42% increased cancer risk (OR = 1.42; 95% CI: 1.02-1.96). Our observations indicate that MTHFR 677TT homozygous individuals are more likely to develop MSI CRC than those with wild type genotype, and this common polymorphism has differential influences on MSI and MSS CRC risk. Stratification by MSI status should aid future studies investigating the complex relationships between genotype, environmental factors and CRC risk. PMID- 17350980 TI - Successful catheter ablation of focal atrial tachycardia from the non-coronary aortic cusp. AB - We describe a patient with frequent episodes of unusual paroxysmal supraventricular tachycardia. During the electrophysiological examination, the tachycardia was easily induced and terminated by atrial pacing. The earliest activation during right atrial activation mapping was located near the atrioventricular node and the His bundle. However, detailed mapping of the aortic root demonstrated that the local activation in the non-coronary aortic cusp preceded the activation at the His bundle region. Radiofrequency catheter ablation at this site terminated the tachycardia with no complications. PMID- 17350981 TI - The contribution of rate adaptive pacing with single or dual sensors to health related quality of life. AB - AIMS: The characteristics of sensors to perform rate adaptive pacing are well established but whether their contribution improves health-related quality of life (QoL) remains disputable. To compare the effects on QoL with an integrated dual sensor [minute ventilation (MV) and acceleration, TT sensor] with a single MV sensor, and with no rate adaptive pacing. METHODS AND RESULTS: This Dutch multi centre, prospective, single- (patient) blind study was performed in patients after first pacemaker (PM) implant for sick sinus syndrome or AV block. After a 3-month 'sensor off'-period following DDD PM implantation, where the latter 2 months permitted the MV sensor to learn the intrinsic rhythm, a 2-month period of DDDR with TT sensor or 2 months of DDDR with MV sensor, subsequently the two modes were crossed over. Quality of life was determined with Aquarel, the disease-specific instrument for PM patients. Heart rate, percentages of sensor driven and intrinsic rhythm were retrieved from PM memories. Sixty-four patients completed the 7-month study. In sick sinus patients, percentages of sensor-driven pacing occurred significantly more frequently than in AV block patients After implant QoL improved significantly: before 71.3 and after 83.5% (P < 0.001) measured with Aquarel and in 3 of 9 SF-36 scales, but no significant additive QoL benefit with dual or MV sensor pacing was observed. Pacing diagnosis, percentages of rate adaptive pacing, and heart rate influencing medication did not influence this result. CONCLUSION: Pacemaker implantation strongly improves QoL, but neither single- nor dual- sensor-driven pacing offered additional improvement in QoL during the initial 8 months after the first PM implant. PMID- 17350982 TI - NIP-141, a multiple ion channel blocker, terminates aconitine-induced atrial fibrillation and prevents the rapid pacing-induced atrial effective refractory period shortening in dogs. AB - AIMS: NIP-141 is a novel multiple ion channel blocker with atrial selective effects. In this study, we examined the effects of NIP-141 on aconitine-induced atrial fibrillation (AF) and rapid atrial pacing-induced atrial effective refractory period (ERP) shortening in dogs. METHODS AND RESULTS: Aconitine AF was induced by the application of aconitine on the right appendage. NIP-141 (10 mg/kg) converted AF to sinus rhythm in 5 of 6 dogs. The Na(+) channel blockers disopyramide (1 mg/kg) and phenytoin (10 mg/kg) also terminated AF, but the I(Kr) blocker (d-sotalol; 4 mg/kg) and a Ca(2+) channel blocker (verapamil; 0.3 mg/kg) did not terminate AF in this model. To clarify the mechanism of AF termination, we examined the effects on ERP and conduction time, but NIP-141 (10 mg/kg) had no significant effects. In a short-term rapid atrial pacing model, NIP-141 (2.5 mg/kg/10 min, followed by 0.033 mg/kg/min) prevented atrial ERP shortening. We also found NIP-141 bound to Na(+) channel site 2 receptor and L-type Ca(2+) channel, but not to Na(+) channel site 1 receptor using radioligands binding assay. CONCLUSION: NIP-141 terminated AF in aconitine-induced AF and prevented the atrial remodelling by short-term rapid pacing in dogs, possibly via the blocking of Na(+) and Ca(2+) channels. PMID- 17350983 TI - Evolution of left ventricular function in paediatric patients with permanent right ventricular pacing for isolated congenital heart block: a medium term follow-up. AB - AIMS: We aimed to assess the evolution of left ventricular (LV) systolic function in children with right ventricular apical (RVA) pacing for isolated congenital heart block (ICHB) and to identify possible predictors of LV function deterioration. Right ventricular apical pacing can be detrimental to LV function in a significant number of adults. Effects in children are still controversial. METHODS AND RESULTS: Left ventricular shortening fraction (LV SF) and QRS duration were retrospectively assessed in 45 children with RVA pacing for ICHB: before pacemaker (PM) implantation, immediately after and then regularly during a follow-up of 58.69 +/- 45.23 months. Patients were categorized as stable or deteriorators according to an arbitrarily chosen cut-off point of > or =7% decrease in LV SF. Lupus status was unknown. Overall LV SF did not change significantly (41.42% +/- 8.21 before pacing, 39.77% +/- 7.03 immediately after PM implant, 37.43% +/- 9.91 with chronic pacing, P = NS). Deteriorators (n = 13) had significantly higher baseline heart rate (57.5 +/- 8.7 vs. 46.9 +/- 10.5 bpm, P < 0.05) and baseline LV SF (46.17 +/- 8.13 vs. 38.4 +/- 6.4%; P < 0.05), a significantly higher proportion of them being implanted before 2 years of age: 8 of 13 (61.5%) vs. 5 of 25 (20%) in the stable group (P < 0.05). Deteriorators had a higher incidence of an initial epicardial lead and narrower native QRS. CONCLUSION: Permanent RVA pacing for ICHB does not necessarily affect LV function in children. The risk of deterioration of LV function seems to be higher in children with higher baseline heart rate and better baseline LV SF, especially with pacing at a younger age, a narrower native QRS and RVA epicardial pacing site. PMID- 17350984 TI - Internal atrial shock delivery by standard diagnostic electrophysiology catheters in goats: effects on atrial electrogram amplitude and tissue architecture. AB - AIMS: In this study, we evaluated the effects of atrial shock delivered via diagnostic electrophysiology catheters. METHODS AND RESULTS: In 11 anaesthetized goats, decapolar catheters were positioned in the right atrial appendage (RAA) and coronary sinus (CS). Three different catheters and two cardioversion protocols were evaluated. In four goats, 50 J shocks were delivered using catheters with 1 mm electrodes (surface area 70 mm(2)). In 6 goats, catheters with 2 mm electrodes (area 140 mm(2)) were used. In three of the six goats, 50 J shocks were given while in the other 3, 10 J shocks were delivered. In 1 goat 50 J shocks were delivered via 5 mm electrode catheters (area 310 mm(2)). No persisting adverse effects occurred. However, the electrogram amplitude at the RAA and CS decreased by >50-98% (P > 0.01). The amount of amplitude decrease was most pronounced at the CS site and for 50 J shocks. Goats were sacrificed after 9 +/- 1 days. Macroscopy revealed endocardial lesions at the electrode locations. Microscopy showed endocardial thrombosis, and necrosis with formation of granulation tissue. Changes were most marked with diagnostic catheters and 50 J shocks. CONCLUSIONS: Atrial shock delivery via diagnostic catheters causes local ablation lesions. The amount of amplitude decrease, macroscopic and microscopic damages were related to the energy applied and electrode surface area. PMID- 17350985 TI - In vitro activity against anaerobes of retapamulin, a new topical antibiotic for treatment of skin infections. AB - OBJECTIVES: Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections. The aim of this study was to determine the antimicrobial activity of retapamulin by determining the minimal inhibitory concentration (MIC) values of this new drug and comparators against a wide range of anaerobic bacteria of human origin. METHODS: The in vitro activity of retapamulin and six comparators (amoxicillin, amoxicillin/clavulanic acid, ceftriaxone, imipenem, clindamycin and metronidazole) was evaluated against 232 anaerobic clinical isolates. MICs were determined by the CLSI reference agar dilution method (M11-A6). RESULTS: Ceftriaxone, clindamycin and amoxicillin/clavulanic acid resistance rates were 54%, 42% and 9.6%, respectively, within the Bacteroides fragilis group. Despite high resistance rates to various antibiotics, retapamulin inhibited 37/52 (71%) strains of the B. fragilis group and 85/87 (98%) of the other Gram-negative bacilli at a concentration of 2 mg/L or less. All the investigated strains of Clostridium perfringens were inhibited by 1 mg/L retapamulin. Three strains of C. difficile and one strain of C. clostridioforme demonstrated decreased susceptibility to retapamulin. Based on inhibitory concentrations, retapamulin was more active than clindamycin, metronidazole and ceftriaxone against Propionibacterium acnes and anaerobic Gram-positive cocci, as all isolates were inhibited by 4 mg/L). The majority of the resistant strains harboured point mutations in their rpoB genes at codons 530, 540 and 545 and showed cross-resistance to rifabutin. Four clinical isolates with moderate rifampicin resistance (8 mg/L) showed a rifabutin-susceptible phenotype and did not harbour any mutation in the sequenced rpoB fragments. Sequence analysis of 100 rifampicin-susceptible isolates revealed numerous novel silent mutations in the rpoB genes resulting in amino acid exchanges, but not in resistance. CONCLUSIONS: Resistance to rifampicin/rifabutin in H. pylori strains isolated in Germany is still low and is associated with mutations in the rpoB gene. Further surveillance studies analysing the use of rifabutin in H. pylori eradication and its association with the occurrence of rifabutin-resistant strains are required. PMID- 17350990 TI - Exploratory study comparing the metabolic toxicities of a lopinavir/ritonavir plus saquinavir dual protease inhibitor regimen versus a lopinavir/ritonavir plus zidovudine/lamivudine nucleoside regimen. AB - OBJECTIVES: To assess the safety, efficacy and metabolic toxicity of lopinavir/ritonavir + saquinavir or zidovudine/lamivudine and evaluate the pharmacokinetics of lopinavir/ritonavir + saquinavir. METHODS: HIV-1-infected, antiretroviral-naive subjects were randomized to lopinavir/ritonavir (400/100 mg) twice daily + saquinavir (800 mg) or zidovudine/lamivudine (150/300 mg) in a Phase II, 48 week study. Subjects receiving lopinavir/ritonavir + zidovudine/lamivudine initiated escalating doses of saquinavir (400, 600 and 800 mg) weekly for 3 weeks. RESULTS: By intent-to-treat (non-completer = failure) analysis, 10/16 (63%) lopinavir/ritonavir + saquinavir-treated and 7/14 (50%) lopinavir/ritonavir + zidovudine/lamivudine-treated subjects achieved plasma HIV 1 RNA <50 copies/mL (P=0.713) at week 48. Safety, tolerability, metabolic changes and truncal fat increases were similar between groups. Small decreases in the lower extremity fat in the zidovudine/lamivudine group (-6%) and a statistically significant increase in the lower extremity fat in the saquinavir group (+19%) were observed. Lopinavir/ritonavir co-administered with saquinavir 600 or 800 mg twice daily produced saquinavir concentrations similar to those previously reported for saquinavir/ritonavir 1000/100 mg twice daily. CONCLUSIONS: Treatment regimens had similar efficacy and tolerability. Metabolic parameters suggested lipoatrophy in the zidovudine/lamivudine treatment group. Saquinavir 600 and 800 mg twice daily produced concentrations similar to those previously reported for saquinavir/ritonavir 1000/100 mg twice daily. PMID- 17350991 TI - Hydromineral neuroendocrinology: mechanism of sensing sodium levels in the mammalian brain. AB - Dehydration causes an increase in the sodium (Na) concentration and osmolarity of body fluids. For Na homeostasis of the body, control of Na and water intake and excretion are of prime importance. Although the circumventricular organs (CVOs) were suggested to be involved in body-fluid homeostasis, the system for sensing Na levels within the brain, which is responsible for the control of Na- and water intake behaviour, has long been an enigma. Na(x) is an atypical sodium channel that is assumed to be a descendant of the voltage-gated sodium channel family. Our studies on the Na(x)-gene-targeting (Na(x)(-/-)) mouse revealed that Na(x) channels are localized to the CVOs and serve as a sodium-level sensor of body fluids. As the first step to understand the cellular mechanism by which the information sensed by Na(x) channels is reflected in the activity of the organs, we dissected the subcellular distribution of Na(x). Double-immunostaining and immuno-electron microscopic analyses revealed that Na(x) is exclusively localized to perineuronal lamellate processes extending from ependymal cells and astrocytes in the organs. In addition, glial cells isolated from the subfornical organ were sensitive to an increase in the extracellular sodium level, as analysed by an ion imaging method. These results suggest that glial cells bearing Na(x) channels are the first to sense a physiological increase in the level of sodium in body fluids, and regulate the neural activity of the CVOs by enveloping neurons. Close communication between inexcitable glial cells and excitable neural cells thus appears to be the basis of the central control of salt homeostasis. PMID- 17350992 TI - Role of TRPV ion channels in sensory transduction of osmotic stimuli in mammals. AB - In signal transduction of metazoan cells, ion channels of the family of transient receptor potential (TRP) have been identified to respond to diverse external and internal stimuli, amongst them osmotic stimuli. This report highlights findings pertaining to the TRPV subfamily, focusing on mammalian members. Of the six mammalian TRPV channels, TRPV1, 2 and 4 were demonstrated to function in transduction of osmotic stimuli. TRPV channels have been found to function in cellular as well as systemic osmotic homeostasis. In a striking example of evolutionary conservation of function, mammalian TRPV4 has been found to rescue osmosensory deficits of the TRPV mutant strain osm-9 in Caenorhabditis elegans, despite not more than 26% orthology of the respective proteins. PMID- 17350993 TI - Neurophysiological characterization of mammalian osmosensitive neurones. AB - In mammals, the osmolality of the extracellular fluid is maintained near a predetermined set-point through a negative feedback regulation of thirst, diuresis, salt appetite and natriuresis. This homeostatic control is believed to be mediated by osmosensory neurones which synaptically regulate the electrical activity of command neurones that mediate each of these osmoregulatory effector responses. Our present understanding of the molecular, cellular and network basis that underlies the central control of osmoregulation is largely derived from studies on primary osmosensory neurones in the organum vasculosum lamina terminalis (OVLT) and effector neurones in the supraoptic nucleus (SON), which release hormones that regulate diuresis and natriuresis. Primary osmosensory neurones in the OVLT exhibit changes in action potential firing rate that vary in proportion with ECF osmolality. This effect results from the intrinsic depolarizing receptor potential which these cells generate via a molecular transduction complex that may comprise various members of the transient receptor potential vanilloid (TRPV) family of cation channel proteins, notably TRPV1 and TRPV4. Osmotically evoked changes in the firing rate of OVLT neurones then regulate the electrical activity of downstream neurones in the SON through graded changes in glutamate release. PMID- 17350994 TI - Transient dynamics of genetic regulatory networks. AB - We present an approximation scheme for deriving reaction rate equations of genetic regulatory networks. This scheme predicts the timescales of transient dynamics of such networks more accurately than does standard quasi-steady state analysis by introducing prefactors to the ODEs that govern the dynamics of the protein concentrations. These prefactors render the ODE systems slower than their quasi-steady state approximation counterparts. We introduce the method by examining a positive feedback gene regulatory network, and show how the transient dynamics of this network are more accurately modeled when the prefactor is included. Next, we examine the repressilator, a genetic oscillator, and show that the period, amplitude, and bifurcation diagram defining the onset of the oscillations are better estimated by the prefactor method. Finally, we examine the consequences of the method to the dynamics of reduced models of the phage lambda switch, and show that the switching times between the two states is slowed by the presence of the prefactor that arises from protein multimerization and DNA binding. PMID- 17350995 TI - Quantifying robustness and dissipation cost of yeast cell cycle network: the funneled energy landscape perspectives. AB - We study the origin of robustness of yeast cell cycle cellular network through uncovering its underlying energy landscape. This is realized from the information of the steady-state probabilities by solving a discrete set of kinetic master equations for the network. We discovered that the potential landscape of yeast cell cycle network is funneled toward the global minimum, G1 state. The ratio of the energy gap between G1 and average versus roughness of the landscape termed as robustness ratio (RR) becomes a quantitative measure of the robustness and stability for the network. The funneled landscape is quite robust against random perturbations from the inherent wiring or connections of the network. There exists a global phase transition between the more sensitive response or less self degradation phase leading to underlying funneled global landscape with large RR, and insensitive response or more self-degradation phase leading to shallower underlying landscape of the network with small RR. Furthermore, we show that the more robust landscape also leads to less dissipation cost of the network. Least dissipation and robust landscape might be a realization of Darwinian principle of natural selection at cellular network level. It may provide an optimal criterion for network wiring connections and design. PMID- 17350997 TI - Numerical Matrices Method for nonlinear system identification and description of dynamics of biochemical reaction networks. AB - A flexible Numerical Matrices Method (NMM) for nonlinear system identification has been developed based on a description of the dynamics of the system in terms of kinetic complexes. A set of related methods are presented that include increasing amounts of prior information about the reaction network structure, resulting in increased accuracy of the reconstructed rate constants. The NMM is based on an analytical least squares solution for a set of linear equations to determine the rate parameters. In the absence of prior information, all possible unimolecular and bimolecular reactions among the species in the system are considered, and the elements of a general kinetic matrix are determined. Inclusion of prior information is facilitated by formulation of the kinetic matrix in terms of a stoichiometry matrix or a more general set of representation matrices. A method for determination of the stoichiometry matrix beginning only with time-dependent concentration data is presented. In addition, we demonstrate that singularities that arise from linear dependencies among the species can be avoided by inclusion of data collected from a number of different initial states. The NMM provides a flexible set of tools for analysis of complex kinetic data, in particular for analysis of chemical and biochemical reaction networks. PMID- 17350996 TI - Quantitative vibrational dynamics of iron in carbonyl porphyrins. AB - We use nuclear resonance vibrational spectroscopy and computational predictions based on density functional theory (DFT) to explore the vibrational dynamics of (57)Fe in porphyrins that mimic the active sites of histidine-ligated heme proteins complexed with carbon monoxide. Nuclear resonance vibrational spectroscopy yields the complete vibrational spectrum of a Mossbauer isotope, and provides a valuable probe that is not only selective for protein active sites but quantifies the mean-squared amplitude and direction of the motion of the probe nucleus, in addition to vibrational frequencies. Quantitative comparison of the experimental results with DFT calculations provides a detailed, rigorous test of the vibrational predictions, which in turn provide a reliable description of the observed vibrational features. In addition to the well-studied stretching vibration of the Fe-CO bond, vibrations involving the Fe-imidazole bond, and the Fe-N(pyr) bonds to the pyrrole nitrogens of the porphyrin contribute prominently to the observed experimental signal. All of these frequencies show structural sensitivity to the corresponding bond lengths, but previous studies have failed to identify the latter vibrations, presumably because the coupling to the electronic excitation is too small in resonance Raman measurements. We also observe the FeCO bending vibrations, which are not Raman active for these unhindered model compounds. The observed Fe amplitude is strongly inconsistent with three-body oscillator descriptions of the FeCO fragment, but agrees quantitatively with DFT predictions. Over the past decade, quantum chemical calculations have suggested revised estimates of the importance of steric distortion of the bound CO in preventing poisoning of heme proteins by carbon monoxide. Quantitative agreement with the predicted frequency, amplitude, and direction of Fe motion for the FeCO bending vibrations provides direct experimental support for the quantum chemical description of the energetics of the FeCO unit. PMID- 17350998 TI - C-phycocyanin hydration water dynamics in the presence of trehalose: an incoherent elastic neutron scattering study at different energy resolutions. AB - We present a study of C-phycocyanin hydration water dynamics in the presence of trehalose by incoherent elastic neutron scattering. By combining data from two backscattering spectrometers with a 10-fold difference in energy resolution we extract a scattering law S(Q,omega) from the Q-dependence of the elastic intensities without sampling the quasielastic range. The hydration water is described by two dynamically different populations--one diffusing inside a sphere and the other diffusing quasifreely--with a population ratio that depends on temperature. The scattering law derived describes the experimental data from both instruments excellently over a large temperature range (235-320 K). The effective diffusion coefficient extracted is reduced by a factor of 10-15 with respect to bulk water at corresponding temperatures. Our approach demonstrates the benefits and the efficiency of using different energy resolutions in incoherent elastic neutron scattering over a large angular range for the study of biological macromolecules and hydration water. PMID- 17350999 TI - The influence of protonation states on the dynamics of the NhaA antiporter from Escherichia coli. AB - The crystal structure of NhaA Na(+)/H(+) antiporter of Escherichia coli has provided a basis to explore the mechanism of Na(+) and H(+) exchange and its regulation by pH. However, the dynamics and nature of the pH-induced changes in the proteins remained unknown. Using molecular mechanics methods, we studied the dynamic behavior of the hydrogen-bonded network in NhaA on shifting the pH from 4 to 8. The helical regions preserved the general architecture of NhaA throughout the pH change. In contrast, large conformational drifts occurred at pH 8 in the loop regions, and an increased flexibility of helix IVp was observed on the pH shift. A remarkable pH-induced conformational reorganization was found: at acidic pH helix X is slightly curved, whereas at alkaline pH, it is kinked around residue Lys(300). The barrier that exists between the cytoplasmic and periplasmic funnels at low pH is removed, and the two funnels are bridged by hydrogen bonds between water molecules and residues located in the TMSs IV/XI assembly and helix X at alkaline pH. In the variant Gly(338)Ser that lost pH control, a hydrogen bonded chain between Ser(338) and Lys(300) was found to block the pH-induced conformational reorganization of helix X. PMID- 17351000 TI - Refinement of the AMBER force field for nucleic acids: improving the description of alpha/gamma conformers. AB - We present here the parmbsc0 force field, a refinement of the AMBER parm99 force field, where emphasis has been made on the correct representation of the alpha/gamma concerted rotation in nucleic acids (NAs). The modified force field corrects overpopulations of the alpha/gamma = (g+,t) backbone that were seen in long (more than 10 ns) simulations with previous AMBER parameter sets (parm94 99). The force field has been derived by fitting to high-level quantum mechanical data and verified by comparison with very high-level quantum mechanical calculations and by a very extensive comparison between simulations and experimental data. The set of validation simulations includes two of the longest trajectories published to date for the DNA duplex (200 ns each) and the largest variety of NA structures studied to date (15 different NA families and 97 individual structures). The total simulation time used to validate the force field includes near 1 mus of state-of-the-art molecular dynamics simulations in aqueous solution. PMID- 17351001 TI - Numerical calculations of single-cell electroporation with an electrolyte-filled capillary. AB - An electric field is focused on one cell in single-cell electroporation. This enables selective electroporation treatment of the targeted cell without affecting its neighbors. While factors that lead to membrane permeation are the same as in bulk electroporation, quantitative description of the single-cell experiments is more complicated. This is due to the fact that the potential distribution cannot be solved analytically. We present single-cell electroporation with an electrolyte-filled capillary modeled with a finite element method. Potential is calculated in the capillary, the solution surrounding the cell, and the cell. The model enables calculation of the transmembrane potential and the fraction of the cell membrane that is above the critical electroporation potential. Electroporation at several cell-to-tip distances of human lung carcinoma cells (A549) stained with ThioGlo-1 demonstrated membrane permeation at distances shorter than approximately 7.0 microm. This agrees well with the model's prediction that a critical transmembrane potential of 250 mV is achieved when the capillary is approximately 6.5 microm or closer to the cell. Simulations predict that at short cell-to-tip distances, the transmembrane potential increases significantly while the total area of the cell above the critical potential increases only moderately. PMID- 17351002 TI - Field theoretic study of bilayer membrane fusion III: membranes with leaves of different composition. AB - We extend previous work on homogeneous bilayers to calculate the barriers to fusion of planar bilayers that contain two different amphiphiles, a lamellar former and a hexagonal former, with different compositions of the two in each leaf. Self-consistent field theory is employed, and both standard and alternative pathways are explored. We first calculate these barriers as the amount of hexagonal former is increased equally in both leaves to levels appropriate to the plasma membrane of human red blood cells. We follow these barriers as the composition of hexagonal formers is then increased in the cis layer and decreased in the trans layer, again to an extent comparable to the biological system. We find that, while the fusion pathway exhibits two barriers in both the standard and alternative pathways, in both cases the magnitudes of these barriers are comparable to one another, and small, on the order of 13 k(B)T. As a consequence, one expects that once the bilayers are brought sufficiently close to one another to initiate the process, fusion should occur rapidly. PMID- 17351004 TI - Origin of bistability in the lac Operon. AB - Multistability is an emergent dynamic property that has been invoked to explain multiple coexisting biological states. In this work, we investigate the origin of bistability in the lac operon. To do this, we develop a mathematical model for the regulatory pathway in this system and compare the model predictions with other experimental results in which a nonmetabolizable inducer was employed. We investigate the effect of lactose metabolism using this model, and show that it greatly modifies the bistable region in the external lactose (Le) versus external glucose (Ge) parameter space. The model also predicts that lactose metabolism can cause bistability to disappear for very low Ge. We have also carried out stochastic numerical simulations of the model for several values of Ge and Le. Our results indicate that bistability can help guarantee that Escherichia coli consumes glucose and lactose in the most efficient possible way. Namely, the lac operon is induced only when there is almost no glucose in the growing medium, but if Le is high, the operon induction level increases abruptly when the levels of glucose in the environment decrease to very low values. We demonstrate that this behavior could not be obtained without bistability if the stability of the induced and uninduced states is to be preserved. Finally, we point out that the present methods and results may be useful to study the emergence of multistability in biological systems other than the lac operon. PMID- 17351003 TI - Pacemaking through Ca2+ stores interacting as coupled oscillators via membrane depolarization. AB - This study presents an investigation of pacemaker mechanisms underlying lymphatic vasomotion. We tested the hypothesis that active inositol 1,4,5-trisphosphate receptor (IP(3)R)-operated Ca(2+) stores interact as coupled oscillators to produce near-synchronous Ca(2+) release events and associated pacemaker potentials, this driving action potentials and constrictions of lymphatic smooth muscle. Application of endothelin 1 (ET-1), an agonist known to enhance synthesis of IP(3), to quiescent lymphatic smooth muscle syncytia first enhanced spontaneous Ca(2+) transients and/or intracellular Ca(2+) waves. Larger near synchronous Ca(2+) transients then occurred leading to global synchronous Ca(2+) transients associated with action potentials and resultant vasomotion. In contrast, blockade of L-type Ca(2+) channels with nifedipine prevented ET-1 from inducing near-synchronous Ca(2+) transients and resultant action potentials, leaving only asynchronous Ca(2+) transients and local Ca(2+) waves. These data were well simulated by a model of lymphatic smooth muscle with: 1), oscillatory Ca(2+) release from IP(3)R-operated Ca(2+) stores, which causes depolarization; 2), L-type Ca(2+) channels; and 3), gap junctions between cells. Stimulation of the stores caused global pacemaker activity through coupled oscillator-based entrainment of the stores. Membrane potential changes and positive feedback by L type Ca(2+) channels to produce more store activity were fundamental to this process providing long-range electrochemical coupling between the Ca(2+) store oscillators. We conclude that lymphatic pacemaking is mediated by coupled oscillator-based interactions between active Ca(2+) stores. These are weakly coupled by inter- and intracellular diffusion of store activators and strongly coupled by membrane potential. Ca(2+) store-based pacemaking is predicted for cellular systems where: 1), oscillatory Ca(2+) release induces depolarization; 2), membrane depolarization provides positive feedback to induce further store Ca(2+) release; and 3), cells are interconnected. These conditions are met in a surprisingly large number of cellular systems including gastrointestinal, lymphatic, urethral, and vascular tissues, and in heart pacemaker cells. PMID- 17351005 TI - Unfolding of beta-sheet proteins in SDS. AB - Beta-sheet proteins are particularly resistant to denaturation by sodium dodecyl sulfate (SDS). Here we compare unfolding of two beta-sandwich proteins TNfn3 and TII27 in SDS. The two proteins show different surface electrostatic potential. Correspondingly, TII27 unfolds below the critical micelle concentration via the formation of hemimicelles on the protein surface, whereas TNfn3 only unfolds around the critical micelle concentration. Isothermal titration calorimetry confirms that unfolding of TII27 sets in at lower SDS concentrations, although the total number of bound SDS molecules is similar at the end of unfolding. In mixed micelles with the nonionic detergent dodecyl maltoside, where the concentration of monomeric SDS is insignificant, the behavior of the two proteins converges. TII27 unfolds more slowly than TNfn3 in SDS and follows a two-mode behavior. Additionally TNfn3 shows inhibition of SDS unfolding at intermediate SDS concentrations. Mutagenic analysis suggests that the overall unfolding mechanism is similar to that observed in denaturant for both proteins. Our data confirm the kinetic robustness of beta-sheet proteins toward SDS. We suggest this is related to the inability of SDS to induce significant amounts of alpha-helix structure in these proteins as part of the denaturation process, forcing the protein to denature by global rather than local unfolding. PMID- 17351006 TI - Different dark conformations function in color-sensitive photosignaling by the sensory rhodopsin I-HtrI complex. AB - The haloarchaeal phototaxis receptor sensory rhodopsin I (SRI) in complex with its transducer HtrI delivers an attractant signal from excitation with an orange photon and a repellent signal from a second near-UV photon excitation. Using a proteoliposome system with purified SRI in complex with its transducer HtrI, we identified by site-directed fluorescence labeling a site (Ser(155)) on SRI that is conformationally active in signal relay to HtrI. Using site-directed spin labeling of Ser(155)Cys with a nitroxide side chain, we detected a change in conformation following one-photon excitation such that the spin probe exhibits a splitting of the outer hyperfine extrema (2A'(zz)) significantly smaller than that of the electron paramagnetic resonance spectrum in the dark state. The dark conformations of five mutant complexes that do not discriminate between orange and near-UV excitation show shifts to lower or higher 2A'(zz) values correlated with the alterations in their motility behavior to one- and two-photon stimuli. These data are interpreted in terms of a model in which the dark complex is populated by two conformers in the wild type, one that inhibits the CheA kinase (A) and the other that activates it (R), shifted in the dark by mutations and shifted in the wild-type SRI-HtrI complex in opposite directions by one-photon and two-photon reactions. PMID- 17351007 TI - Force of an actin spring. AB - Cellular movements are produced by forces. Typically, cytoskeletal proteins such as microtubules and actin filaments generate forces via polymerization or in conjunction with molecular motors. However, the fertilization of a Limulus polyphemus egg involves a third type of actin-based cellular engine--a biological spring. During the acrosome reaction, a 60-microm long coiled and twisted bundle of actin filaments straightens and extends from a sperm cell, penetrating the vitelline layer surrounding the egg. A subtle overtwist of 0.2 degrees /subunit underlies the mechanochemical basis for the extension of this actin spring. Upon calcium activation, this conformational strain energy is converted to mechanical work, generating the force required to extend the bundle through the vitelline layer. In this article, we stall the extension of the acrosome bundle in agarose gels of different concentrations. From the stall forces, we estimate a maximum force of 2 nN and a puncturing pressure of 1.6 MPa. We show the maximum force of extension is three times larger than the force required to puncture the vitelline layer. Thus, the elastic strain energy stored in the acrosome bundle is more than sufficient to power the acrosome reaction through the egg envelope. PMID- 17351008 TI - Defining the interface between the C-terminal fragment of alpha-transducin and photoactivated rhodopsin. AB - A novel combination of experimental data and extensive computational modeling was used to explore probable protein-protein interactions between photoactivated rhodopsin (R*) and experimentally determined R*-bound structures of the C terminal fragment of alpha-transducin (Gt(alpha)(340-350)) and its analogs. Rather than using one set of loop structures derived from the dark-adapted rhodopsin state, R* was modeled in this study using various energetically feasible sets of intracellular loop (IC loop) conformations proposed previously in another study. The R*-bound conformation of Gt(alpha)(340-350) and several analogs were modeled using experimental transferred nuclear Overhauser effect data derived upon binding R*. Gt(alpha)(340-350) and its analogs were docked to various conformations of the intracellular loops, followed by optimization of side-chain spatial positions in both R* and Gt(alpha)(340-350) to obtain low energy complexes. Finally, the structures of each complex were subjected to energy minimization using the OPLS/GBSA force field. The resulting residue residue contacts at the interface between R* and Gt(alpha)(340-350) were validated by comparison with available experimental data, primarily from mutational studies. Computational modeling performed for Gt(alpha)(340-350) and its analogs when bound to R* revealed a consensus of general residue-residue interactions, necessary for efficient complex formation between R* and its Gt(alpha) recognition motif. PMID- 17351009 TI - Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites. AB - The free [Ca2+] in endoplasmic/sarcoplasmic reticulum Ca2+ stores regulates excitability of Ca2+ release by stimulating the Ca2+ release channels. Just how the stored Ca2+ regulates activation of these channels is still disputed. One proposal attributes luminal Ca2+-activation to luminal facing regulatory sites, whereas another envisages Ca2+ permeation to cytoplasmic sites. This study develops a unified model for luminal Ca2+ activation for single cardiac ryanodine receptors (RyR2) and RyRs in coupled clusters in artificial lipid bilayers. It is shown that luminal regulation of RyR2 involves three modes of action associated with Ca2+ sensors in different parts of the molecule; a luminal activation site (L-site, 60 microM affinity), a cytoplasmic activation site (A-site, 0.9 microM affinity), and a novel cytoplasmic inactivation site (I2-site, 1.2 microM affinity). RyR activation by luminal Ca2+ is demonstrated to occur by a multistep process dubbed luminal-triggered Ca2+ feedthrough. Ca2+ binding to the L-site initiates brief openings (1 ms duration at 1-10 s(-1)) allowing luminal Ca2+ to access the A-site, producing up to 30-fold prolongation of openings. The model explains a broad data set, reconciles previous conflicting observations and provides a foundation for understanding the action of pharmacological agents, RyR associated proteins, and RyR2 mutations on a range of Ca2+-mediated physiological and pathological processes. PMID- 17351010 TI - Lipid chain-length dependence for incorporation of alamethicin in membranes: electron paramagnetic resonance studies on TOAC-spin labeled analogs. AB - Alamethicin is a 19-residue hydrophobic peptide, which is extended by a C terminal phenylalaninol but lacks residues that might anchor the ends of the peptide at the lipid-water interface. Voltage-dependent ion channels formed by alamethicin depend strongly in their characteristics on chain length of the host lipid membranes. EPR spectroscopy is used to investigate the dependence on lipid chain length of the incorporation of spin-labeled alamethicin in phosphatidylcholine bilayer membranes. The spin-label amino acid TOAC is substituted at residue positions n = 1, 8, or 16 in the sequence of alamethicin F50/5 [TOAC(n), Glu(OMe)(7,18,19)]. Polarity-dependent isotropic hyperfine couplings of the three TOAC derivatives indicate that alamethicin assumes approximately the same location, relative to the membrane midplane, in fluid diC(N)PtdCho bilayers with chain lengths ranging from N = 10-18. Residue TOAC(8) is situated closest to the bilayer midplane, whereas TOAC(16) is located farther from the midplane in the hydrophobic core of the opposing lipid leaflet, and TOAC(1) remains in the lipid polar headgroup region. Orientational order parameters indicate that the tilt of alamethicin relative to the membrane normal is relatively small, even at high temperatures in the fluid phase, and increases rather slowly with decreasing chain length (from 13 degrees to 23 degrees for N = 18 and 10, respectively, at 75 degrees C). This is insufficient for alamethicin to achieve hydrophobic matching. Alamethicin differs in its mode of incorporation from other helical peptides for which transmembrane orientation has been determined as a function of lipid chain length. PMID- 17351011 TI - The structural determinants of macrolide-actin binding: in silico insights. AB - By the use of x-ray structures and flexible docking, we have developed the first in silico ligand-based view of the structural determinants of the binding of small molecule mimics of gelsolin, natural products bound to actin. Our technique highlights those residues on the actin binding site forming important hydrophobic and hydrogen-bonding interactions with the ligands. Significantly, through the flexible docking of toxin fragments, we have also identified potential residues on the actin binding site that have yet to be exploited. Guided by these observations, we have demonstrated that kabiramide C can be modified to produce a structure with a predicted binding energy increased by 20% while the molecular mass is reduced by 20%, clearly indicating the potential for future elaboration of structures targeting this important component of the cytoskeleton. PMID- 17351012 TI - A stable water chain in the hydrophobic pore of the AmtB ammonium transporter. AB - The accessibility of water molecules to the pore of the AmtB ammonium transporter is studied using molecular dynamics simulations. Free energy calculations show that the so-called hydrophobic pore can stabilize a chain of water molecules in a well of a few kcal/mol, using a favorable electrostatic binding pocket as an anchoring point. Moreover, the structure of the water chain matches precisely the electronic density maxima observed in x-ray diffraction experiments. This result questions the general assumption that the AmtB pore only contains ammonia (NH(3)) molecules diffusing in a single file fashion. The probable presence of water molecules in the pore would influence the relative stability of NH(3) and NH(4)(+), and thus calls for a reassessment of the overall permeation mechanism in ammonium transporters. PMID- 17351013 TI - The effect of protein complexation on the mechanical stability of Im9. AB - Force mode microscopy can be used to examine the effect of mechanical manipulation on the noncovalent interactions that stabilize proteins and their complexes. Here we describe the effect of complexation by the high affinity protein ligand E9 on the mechanical resistance of the simple four-helical protein, Im9. When concatenated into a construct of alternating I27 domains, Im9 unfolded below the thermal noise limit of the instrument ( approximately 20 pN). Complexation of E9 had little effect on the mechanical resistance of Im9 (unfolding force approximately 30 pN) despite the high avidity of this complex (K(d) approximately 10 fM). PMID- 17351015 TI - A free-rotating and self-avoiding chain model for deriving statistical potentials based on protein structures. AB - Statistical potentials have been widely used in protein studies despite the much debated theoretical basis. In this work, we have applied two physical reference states for deriving the statistical potentials based on protein structure features to achieve zero interaction and orthogonalization. The free-rotating chain-based potential applies a local free-rotating chain reference state, which could theoretically be described by the Gaussian distribution. The self-avoiding chain-based potential applies a reference state derived from a database of artificial self-avoiding backbones generated by Monte Carlo simulation. These physical reference states are independent of known protein structures and are based solely on the analytical formulation or simulation method. The new potentials performed better and yielded higher Z-scores and success rates compared to other statistical potentials. The end-to-end distance distribution produced by the self-avoiding chain model was similar to the distance distribution of protein atoms in structure database. This fact may partly explain the basis of the reference states that depend on the atom pair frequency observed in the protein database. The current study showed that a more physical reference model improved the performance of statistical potentials in protein fold recognition, which could also be extended to other types of applications. PMID- 17351014 TI - Tetracaine-membrane interactions: effects of lipid composition and phase on drug partitioning, location, and ionization. AB - Interactions of the local anesthetic tetracaine with unilamellar vesicles made of dimyristoyl or dipalmitoyl phosphatidylcholine (DMPC or DPPC), the latter without or with cholesterol, were examined by following changes in the drug's fluorescent properties. Tetracaine's location within the membrane (as indicated by the equivalent dielectric constant around the aromatic fluorophore), its membrane:buffer partition coefficients for protonated and base forms, and its apparent pK(a) when adsorbed to the membrane were determined by measuring, respectively, the saturating blue shifts of fluorescence emission at high lipid:tetracaine, the corresponding increases in fluorescence intensity at this lower wavelength with increasing lipid, and the dependence of fluorescence intensity of membrane-bound tetracaine (TTC) on solution pH. Results show that partition coefficients were greater for liquid-crystalline than solid-gel phase membranes, whether the phase was set by temperature or lipid composition, and were decreased by cholesterol; neutral TTC partitioned into membranes more strongly than the protonated species (TTCH(+)). Tetracaine's location in the membrane placed the drug's tertiary amine near the phosphate of the headgroup, its ester bond in the region of the lipids' ester bonds, and associated dipole field and the aromatic moiety near fatty acyl carbons 2-5; importantly, this location was unaffected by cholesterol and was the same for neutral and protonated tetracaine, showing that the dipole-dipole and hydrophobic interactions are the critical determinants of tetracaine's location. Tetracaine's effective pK(a) was reduced by 0.3-0.4 pH units from the solution pK(a) upon adsorption to these neutral bilayers, regardless of physical state or composition. We propose that the partitioning of tetracaine into solid-gel membranes is determined primarily by its steric accommodation between lipids, whereas in the liquid-crystalline membrane, in which the distance between lipid molecules is larger and steric hindrance is less important, hydrophobic and ionic interactions between tetracaine and lipid molecules predominate. PMID- 17351016 TI - Reciprocal effects of IFN-beta and IL-12 on STAT4 activation and cytokine induction in T cells. AB - IL-12 is an immunoregulatory cytokine, which promotes Th1 cell differentiation and is a major inducer of IFN-gamma. IFN-beta, a Type I IFN used in the treatment of multiple sclerosis, has been shown to significantly increase the expression of the anti-inflammatory cytokine IL-10, a major suppressor of Th1 cytokines. The beneficial immunomodulatory effects of IFN-beta may in part be a result of its ability to suppress IL-12. However, IL-12 and IFN-beta signal via the STAT4 pathway. Our aim was to investigate the relationship between IL-12 and IFN-beta by observing the effect of prior exposure to IL-12 or IFN-beta on the ability of T cells to subsequently respond to the other cytokine. We report that IFN-beta increases IL-12-induced STAT4 phosphorylation and up-regulates IL-12 receptor beta1 and beta2 expression. However, despite this up-regulation, IFN-beta suppressed IL-12-induced IFN-gamma expression. Our results suggest that this may be a result of the parallel induction of IL-10 by IFN-beta. PMID- 17351017 TI - The relaxin family peptide receptor 3 activates extracellular signal-regulated kinase 1/2 through a protein kinase C-dependent mechanism. AB - Human gene 3 relaxin (H3 relaxin) is a member of the relaxin/insulin family of peptides. Neuropeptides mediate behavioral responses to stress and regulates appetite; however, the cell signaling mechanisms that control these events remain to be identified. The relaxin family peptide receptor 3 (RXFP3, formerly GPCR135 or SALPR) was characterized as the receptor for H3 relaxin, functionally coupled to the inhibition of cAMP. We have identified that RXFP3 stably expressed in Chinese hamster ovary (CHO)-K1 (CHO-RXFP3) and human embryonic kidney (HEK) 293 (HEK-RXFP3) cells activates extracellular signal-regulated kinase (ERK) 1/2 when stimulated with H3 relaxin and an H3 relaxin B-chain (dimer) peptide. Using inhibitors of cellular signaling proteins, we subsequently determined the mechanism of ERK1/2 activation by RXFP3. ERK1/2 phosphorylation requires the activation of G(i/o) proteins and seems to require receptor internalization and/or compartmentalization into lipid-rich environments. ERK1/2 activation also predominantly occurred via the activation of a protein kinase C-dependent pathway, although activation of phosphatidylinositol 3-kinase and Src tyrosine kinase were also involved to a lesser extent. The mechanisms underlying ERK1/2 phosphorylation were similar in both CHO-RXFP3 and HEK-RXFP3 cells, although some differences were evident. Phospholipase Cbeta and the transactivation of endogenous epidermal growth factor receptors both played a role in RXFP3-mediated ERK1/2 activation in HEK293 cells; however, they were not involved in RXFP3 mediated ERK1/2 activation in the CHO-K1 cell background. The pathways identified in CHO- and HEK-transfected cells were also used in the murine SN56 neuronal cell line, suggesting that these pathways are also important for RXFP3-mediated signaling in the brain. PMID- 17351018 TI - Engineering of alpha1-antitrypsin variants selective for subtilisin-like proprotein convertases PACE4 and PC6: importance of the P2' residue in stable complex formation of the serpin with proprotein convertase. AB - Furin and PACE4, members of the subtilisin-like proprotein convertase (SPC) family, have been implicated in the metastatic progression of certain tumors in addition to the activation of viral coat proteins and bacterial toxins, indicating that these enzymes are potential targets for therapeutic agents. Alpha1-Antitrypsin Portland is an engineered alpha1-antitrypsin designed as a furin-specific inhibitor and has been used as a tool in the functional analysis of furin. In this work, we engineered rat alpha1-antitrypsin to create a PACE4 specific inhibitor. Substituting Arg-Arg-Arg-Arg for Ala-Val-Pro-Met(352) at P4 P1 and Ala for Leu(354) at P2' created a potent PACE4- and PC6-specific inhibitor. This variant (RRRRSA) formed an SDS- and heat-stable serpin/proteinase complex with PACE4 or PC6 and inhibited both enzyme activities. The RRRRSA variant was efficiently cleaved by furin without formation of the stable complex. This is the first report of a highly selective protein-based inhibitor of PACE4 and PC6. This inhibitor will be useful in delineating the roles of PACE4 and PC6 localized in the extracellular matrix. PMID- 17351019 TI - Directed evolution of Tk-subtilisin from a hyperthermophilic archaeon: identification of a single amino acid substitution responsible for low temperature adaptation. AB - Tk-subtilisin from the hyperthermophilic archaeon Thermococcus kodakaraensis is synthesized in a prepro-form (prepro-Tk-subtilisin), secreted in a pro-form (pro Tk-subtilisin), and matured to an active form (mat-Tk-subtilisin*; a Ca(2+)-bound active form of matured domain of Tk-subtilisin) upon autoprocessing and degradation of the propeptide [Tk-propeptide; propeptide of Tk-subtilisin (Gly1 Leu69)]. Pro-Tk-subtilisin exhibited halo-forming activity only at 80 degrees C, but not at 70 and 60 degrees C, because Tk-propeptide is not effectively degraded by mat-Tk-subtilisin* and forms an inactive complex with mat-Tk-subtilisin* at <80 degrees C. Random mutagenesis in the entire prepro-Tk-subtilisin gene, followed by screening for mutant proteins with halo-forming activity at 70 and 60 degrees C, allowed us to identify single Gly56 --> Ser mutation in the propeptide region responsible for low-temperature adaptation of pro-Tk-subtilisin. SDS-PAGE analyses and mat-Tk-subtilisin* activity assay of pro-G56S-subtilisin indicated more rapid maturation than pro-Tk-subtilisin. The resultant active form was indistinguishable from mat-Tk-subtilisin* in activity and stability, indicating that Gly56 --> Ser mutation does not seriously affect the folding of the mature domain. However, this mutation greatly destabilized the propeptide, making it unstructured in an isolated form. As a result, Tk-propeptide with Gly56 --> Ser mutation (G56S-propeptide) was more susceptible to proteolytic degradation and less effectively inhibited mat-Tk-subtilisin* activity than Tk-propeptide. These results suggest that pro-G56S-subtilisin is more effectively matured than pro-Tk subtilisin at lower temperatures, because autoprocessed G56S-propeptide is unstructured upon dissociation from mat-Tk-subtilisin* and is therefore effectively degraded by mat-Tk-subtilisin*. PMID- 17351021 TI - Editorial: just in cases... PMID- 17351020 TI - MECP2 mutations in males. AB - Rett syndrome (RS; MIM 312750) is a severe neurological disorder affecting exclusively females. Its prevalence is about 1 in 10,000 female births, and it is a prominent cause of profound mental handicap in women. RS is caused by mutations in the X-linked methyl CpG-binding protein 2 (MECP2) gene. These mutations were initially thought to be lethal in males. However, MECP2 mutations are now frequently identified in mentally retarded male patients. The frequency of disease-causing MECP2 mutations in this population is between 1.3% and 1.7%. Surprisingly, MECP2 mutations in males are responsible for a wide spectrum of neurological disorders, ranging from mild mental retardation to severe neonatal encephalopathy. The aim of this review is to describe the nature of the MECP2 mutations identified in male patients to date and their associated phenotypes. PMID- 17351022 TI - A critical review of complementary therapies for cancer-related fatigue. AB - PURPOSE: To review the available literature on the use of complementary and alternative medicine (CAM) treatments for cancer-related fatigue with an aim to develop directions for future research. METHODS: PubMed, EMBASE, CINAHL, PsycINFO, and SPORTDiscus were searched for relevant studies. Original clinical trials reporting on the use of CAM treatments for cancer-related fatigue were abstracted and critically reviewed. RESULTS: CAM interventions tested for cancer related fatigue include acupuncture, aromatherapy, adenosine triphosphate infusions, energy conservation and activity management, healing touch, hypnosis, lectin-standardized mistletoe extract, levocarnitine, massage, mindfulness-based stress reduction, polarity therapy, relaxation, sleep promotion, support group, and Tibetan yoga. Several of these interventions seem promising in initial studies. CONCLUSION: Currently, insufficient data exist to recommend any specific CAM modality for cancer-related fatigue. Therefore, potentially effective CAM interventions ready for further study in large, randomized clinical trials (eg, acupuncture, massage, levocarnitine, and the use of mistletoe) should be pursued. Other interventions should be tested in well-designed feasibility and phase II trials. PMID- 17351023 TI - Effectiveness of CancerGuides a study of an integrative cancer care training program for health professionals. AB - PURPOSE: To determine how CancerGuidesa, an integrative cancer care training program, would affect participants' perception of their professional skills, their mood, use of self care and mind-body modalities, and the acceptance of integrative cancer care at their institutions. STUDY DESIGN: Qualitative and quantitative measures were used during the training program and at 6-month follow up. A focus group met before and after the training, and individual interviews of focus group participants were done at follow-up. METHODS: The week-long program consisted of lectures that provided information on integrating conventional and complementary therapies into individualized programs of cancer care. Small group sessions used mind-body techniques to allow participants to understand the dilemmas faced by cancer patients. A self-report survey was administered at the training program and at 6-month follow-up. The survey included questions on the personal and professional use of modalities and on participants' sense of how well they met the course objectives. Qualitative questions addressed self-care, changes in clinical practice, and the acceptance of integrative therapies by their institutions. The Profile of Mood States was administered before and after the training. RESULTS: Six months after the training, there was a significant increase in the use and/or recommendation of complementary and alternative medicine modalities in clinical practice and a significant increase in the personal practice of these modalities. Participants' perceived level of skill for all of the course objectives was significantly increased following the training and was maintained at 6-month follow-up. There were significant reductions in the Anger-Hostility and Tension-Anxiety subscale scores of the Profile of Mood States questionnaire. In response to qualitative questions, participants reported positive changes in patient care and in their clinical practices at 6-month follow-up. The subset of participants in the focus group interviews reported similar improvements. Thirty-five percent of those responding at follow-up reported an increase in acceptance of integrative cancer therapies at their institutions, and 77% reported making positive changes in self-care. CONCLUSIONS: Cancer-Guides provided training that allowed participants to enhance personal self-care, to interact more effectively with their patients, and to develop programs of integrative cancer care. PMID- 17351024 TI - Pilot crossover trial of Reiki versus rest for treating cancer-related fatigue. AB - Fatigue is an extremely common side effect experienced during cancer treatment and recovery. Limited research has investigated strategies stemming from complementary and alternative medicine to reduce cancer-related fatigue. This research examined the effects of Reiki, a type of energy touch therapy, on fatigue, pain, anxiety, and overall quality of life. This study was a counterbalanced crossover trial of 2 conditions: (1) in the Reiki condition, participants received Reiki for 5 consecutive daily sessions, followed by a 1 week washout monitoring period of no treatments, then 2 additional Reiki sessions, and finally 2 weeks of no treatments, and (2) in the rest condition, participants rested for approximately 1 hour each day for 5 consecutive days, followed by a 1-week washout monitoring period of no scheduled resting and an additional week of no treatments. In both conditions, participants completed questionnaires investigating cancer-related fatigue (Functional Assessment of Cancer Therapy Fatigue subscale [FACT-F]) and overall quality of life (Functional Assessment of Cancer Therapy, General Version [FACT-G]) before and after all Reiki or resting sessions. They also completed a visual analog scale (Edmonton Symptom Assessment System [ESAS]) assessing daily tiredness, pain, and anxiety before and after each session of Reiki or rest. Sixteen patients (13 women) participated in the trial: 8 were randomized to each order of conditions (Reiki then rest; rest then Reiki). They were screened for fatigue on the ESAS tiredness item, and those scoring greater than 3 on the 0 to 10 scale were eligible for the study. They were diagnosed with a variety of cancers, most commonly colorectal (62.5%) cancer, and had a median age of 59 years. Fatigue on the FACT-F decreased within the Reiki condition (P=.05) over the course of all 7 treatments. In addition, participants in the Reiki condition experienced significant improvements in quality of life (FACT-G) compared to those in the resting condition (P <.05). On daily assessments (ESAS) in the Reiki condition, presession 1 versus postsession 5 scores indicated significant decreases in tiredness (P <.001), pain (P <.005), and anxiety (P<.01), which were not seen in the resting condition. Future research should further investigate the impact of Reiki using more highly controlled designs that include a sham Reiki condition and larger sample sizes. PMID- 17351025 TI - Acupuncture for chemotherapy-associated cognitive dysfunction: a hypothesis generating literature review to inform clinical advice. AB - There is an emerging consensus that between one fifth and one half of breast cancer patients experience chemotherapy-associated cognitive dysfunction. Research shows that patients with cancer are often interested in acupuncture for symptom relief. A clinical question thus arises: What should physicians advise their patients regarding the use of acupuncture to alleviate or ameliorate chemotherapy-associated cognitive dysfunction? The authors review and synthesize 2 bodies of relevant research literature: (1) the developing literature on the etiology and nature of chemotherapy-associated cognitive dysfunction and (2) the literature concerning acupuncture for neurological diseases and psychological issues. There is evidence that acupuncture may be effectively used to manage a range of psychoneurological issues, some of which are similar to those experienced by patients with chemotherapy-associated cognitive dysfunction. The evidence of efficacy is more promising for psychological than neurological conditions. Given evidence of possible efficacy combined with evidence of demonstrated safety, we suggest that physicians should support patient decisions to use acupuncture services for chemotherapy-associated cognitive dysfunction, especially given the lack of proven alternatives. PMID- 17351026 TI - Modulation of doxorubicin-induced genotoxicity by Aegle marmelos in mouse bone marrow: a micronucleus study. AB - The effect of various concentrations of Aegle marmelos (AME) on the doxorubicin (DOX)-induced genotoxic effects in mice bone marrow was studied. Treatment of mice with different concentrations of DOX resulted in a dose-dependent elevation in the frequency of micronucleated polychromatic (MPCE) as well as normochromatic (MNCE) erythrocytes in mouse bone marrow. The frequencies of MPCE and MNCE increased with scoring time, and the greatest elevation for MPCE was observed at 48 hours post-DOX treatment, whereas a maximum increase in MNCE was observed at 72 hours post-DOX treatment. This increase in MPCE and MNCE was accompanied by a decline in the polychromatic erythrocytes-normochromatic erythrocytes (PCE/NCE) ratio, which showed a DOX-dose-dependent decline. Treatment of mice with 200, 250, 300, 350, and 400 mg/kg body weight of AME, orally once daily for 5 consecutive days before DOX treatment, significantly reduced the frequency of DOX induced micronuclei accompanied by a significant elevation in the PCE/NCE ratio at all scoring times. The greatest protection against DOX-induced genotoxicity was observed at 350 mg/kg AME. The protection against DOX-induced genotoxicity by AME may be due to inhibition of free radicals and increased antioxidant status. PMID- 17351027 TI - Cytoprotective effect of Podophyllum hexandrum against gamma radiation is mediated via hemopoietic system stimulation and up-regulation of heme-oxygenase-1 and the prosurvival multidomain protein Bcl-2. AB - The radioprotective effect of a hydroalcoholic extracted material (REC-2000) from the rhizome of Podophyllum hexandrum was studied in mice exposed to lethal gamma radiation (10 Gy). The extract (REC-2000) was found to restore the hemoglobin content (14.73 +/- 0.33) and total leukocyte count (TLC) (4166.66 +/- 0.02) in lethally (10 Gy) gamma-irradiated mice on the 15th day in comparison to the radiation control mice. The hemoglobin content of the drug + radiation group was observed to be significantly (21.25%) higher than the radiation control group on the 10th day. Similarly, the TLC was significantly increased (83.33 times) in the drug + radiation group as compared to a radiation (10 Gy) only group on the 10th day. Enhanced expression of heme-oxygenase-1 and Bcl-2 protein observed by Western blotting further supports the observation of hemopoietic recovery in irradiated mice. These findings indicate that the bioactive constituents present in REC-2000 exert the radioprotective effect by modulating the hemopoietic system. PMID- 17351028 TI - Modulation of natural killer cell activity, antibody-dependent cellular cytotoxicity, and antibody-dependent complement-mediated cytotoxicity by andrographolide in normal and Ehrlich ascites carcinoma-bearing mice. AB - Modulation of immune responses is highly relevant in tumor cell destruction. The present study is focused on the effect of Andrographis paniculata extract (APE) and its isolated compound andrographolide (ANDLE) on cell-mediated immune responses in normal and tumor-bearing control animals. Treatment with APE and ANDLE significantly enhanced natural killer cell activity in normal (APE, 46.82% cell lysis; ANDLE, 40.79% cell lysis) and tumor-bearing animals (APE, 48.66% cell lysis; ANDLE, 42.19% cell lysis) on the fifth day, and it was observed earlier than in tumor-bearing control animals (12.89% cell lysis on day 9). Antibody dependent cellular cytotoxicity was also increased in APE (45.17% cell lysis on day 11) as well as ANDLE (39.92% cell lysis on day 11)-treated normal and tumor bearing animals (APE, 47.39% cell lysis; ANDLE, 41.48% cell lysis on day 11) compared to untreated tumor-bearing control animals (maximum of 11.76% cell lysis on day 17). An early enhancement of antibody-dependent complement-mediated cytotoxicity was also observed by the administration of APE and ANDLE in normal as well as tumor-bearing animals. APE and ANDLE administration could significantly enhance the mitogen-induced proliferation of splenocyte, thymocyte, and bone marrow cells. Moreover, treatment of APE and ANDLE significantly elevated the production of interleukin-2 and interferon-gamma in normal and Ehrlich ascites carcinoma-bearing animals. PMID- 17351029 TI - The role of Zyflamend, an herbal anti-inflammatory, as a potential chemopreventive agent against prostate cancer: a case report. AB - Correlation between dietary intake and occurrence of prostate cancer has gained significant support in recent years. Although a direct correlation has yet to be proven between inflammation and prostate cancer, chronic or recurrent inflammation has been hypothesized to be the major predisposing factor for this disease. The authors have been studying Zyflamend, a novel herbal anti inflammatory mixture, as a potential chemopreventive agent in a phase 1 trial for patients diagnosed with prostatic intraepithelial neoplasia. They report the results of the first patient who has completed the 18-month study in which 24 patients were assigned to a cohort and placed on successive herbal supplement regimen starting with Zyflamend alone. PMID- 17351030 TI - Surviving against all odds: analysis of 6 case studies of patients with cancer who followed the Gerson therapy. AB - A considerable number of patients with cancer have used or are using the Gerson therapy, an alleged anticancer metabolic diet. However, there is almost no scientific support for this regimen. Hence, the present case review study of 6 patients with metastatic cancer who used the Gerson therapy aims at critically evaluating each case to derive some valid interpretations of its potential effect. All 6 cases had a cancer diagnosis with poor prognosis. Despite the presence of some confounding variables, it seems that the Gerson regimen has supported patients to some extent both physically and psychologically. More scientific attention needs to be directed to this area so that patients can practice safe and appropriate therapies that are based on evidence rather than anecdotes. PMID- 17351031 TI - Integrating Chinese and conventional medicine in colorectal cancer treatment. AB - The Chinese have been integrating cancer treatment for the past 60 years. Using conventional and Chinese traditional medicine, this integration has evolved into a sophisticated hybrid of medicine that has generated a great deal of well designed research demonstrating that the use of combined care can improve outcomes for patients with cancer. This article seeks to explain the integration in terms of treatment of colorectal cancer and a colorectal cancer case with Duke's stage C adenocarcinoma. PMID- 17351032 TI - Degradation of alkyl methyl ketones by Pseudomonas veronii MEK700. AB - Pseudomonas veronii MEK700 was isolated from a biotrickling filter cleaning 2 butanone-loaded waste air. The strain is able to grow on 2-butanone and 2 hexanol. The genes for degradation of short chain alkyl methyl ketones were identified by transposon mutagenesis using a newly designed transposon, mini Tn5495, and cloned in Escherichia coli. DNA sequence analysis of a 15-kb fragment revealed three genes involved in methyl ketone degradation. The deduced amino acid sequence of the first gene, mekA, had high similarity to Baeyer-Villiger monooxygenases; the protein of the second gene, mekB, had similarity to homoserine acetyltransferases; the third gene, mekR, encoded a putative transcriptional activator of the AraC/XylS family. The three genes were located between two gene groups: one comprising a putative phosphoenolpyruvate synthase and glycogen synthase, and the other eight genes for the subunits of an ATPase. Inactivation of mekA and mekB by insertion of the mini-transposon abolished growth of P. veronii MEK700 on 2-butanone and 2-hexanol. The involvement of mekR in methyl ketone degradation was observed by heterologous expression of mekA and mekB in Pseudomonas putida. A fragment containing mekA and mekB on a plasmid was not sufficient to allow P. putida KT2440 to grow on 2-butanone. Not until all three genes were assembled in the recombinant P. putida was it able to use 2 butanone as carbon source. The Baeyer-Villiger monooxygenase activity of MekA was clearly demonstrated by incubating a mekB transposon insertion mutant of P. veronii with 2-butanone. Hereby, ethyl acetate was accumulated. To our knowledge, this is the first time that ethyl acetate by gas chromatographic analysis has been definitely demonstrated to be an intermediate of MEK degradation. The mekB encoded protein was heterologously expressed in E. coli and purified by immobilized metal affinity chromatography. The protein exhibited high esterase activity towards short chain esters like ethyl acetate and 4-nitrophenyl acetate. PMID- 17351033 TI - TraY and integration host factor oriT binding sites and F conjugal transfer: sequence variations, but not altered spacing, are tolerated. AB - Bacterial conjugation is the process by which a single strand of a conjugative plasmid is transferred from donor to recipient. For F plasmid, TraI, a relaxase or nickase, binds a single plasmid DNA strand at its specific origin of transfer (oriT) binding site, sbi, and cleaves at a site called nic. In vitro studies suggest TraI is recruited to sbi by its accessory proteins, TraY and integration host factor (IHF). TraY and IHF bind conserved oriT sites sbyA and ihfA, respectively, and bend DNA. The resulting conformational changes may propagate to nic, generating the single-stranded region that TraI can bind. Previous deletion studies performed by others showed transfer efficiency of a plasmid containing F oriT decreased progressively as increasingly longer segments, ultimately containing both sbyA and ihfA, were deleted. Here we describe our efforts to more precisely define the role of sbyA and ihfA by examining the effects of multiple base substitutions at sbyA and ihfA on binding and plasmid mobilization. While we observed significant decreases in in vitro DNA-binding affinities, we saw little effect on plasmid mobilization even when sbyA and ihfA variants were combined. In contrast, when half or full helical turns were inserted between the relaxosome protein-binding sites, mobilization was dramatically reduced, in some cases below the detectable limit of the assay. These results are consistent with TraY and IHF recognizing sbyA and ihfA with limited sequence specificity and with relaxosome proteins requiring proper spacing and orientation with respect to each other. PMID- 17351034 TI - Target site selection of Pseudomonas putida transposon Tn4652. AB - We analyzed the target preferences of a Tn3 family transposon Tn4652. Alignment of 93 different insertion sites revealed a consensus sequence which resembles that of Tn3, indicating that despite a low similarity between Tn4652 and Tn3 transposases, their target site recognition is conserved. PMID- 17351035 TI - XphA/XqhA, a novel GspCD subunit for type II secretion in Pseudomonas aeruginosa. AB - The opportunistic human pathogen bacterium Pseudomonas aeruginosa secretes various exoproteins in its surrounding environment. Protein secretion involves different secretory systems, including the type II secretion system, or T2SS, that is one of the most efficient secretory pathways of P. aeruginosa. There are two T2SS in this bacterium, the quorum-sensing-regulated Xcp system and the Hxc system, which is only present under phosphate-limiting conditions. Like T2SS of other bacteria, the Xcp T2SS is species specific, and this specificity mainly involves two proteins, XcpP (GspC family) and the secretin XcpQ (GspD family), which are the gatekeepers of the system. Interestingly, an orphan secretin, XqhA, was previously reported as being able to functionally replace the XcpQ secretin. In this study, we identified another gene, which we named xphA (xcpP homologue A), which is located next to xqhA. We showed that deletion of the xphA gene in an xcpP mutant caused the disappearance of the residual secretion observed in this mutant strain, indicating that the protein XphA plays a role in the secretion process. Our results also revealed that complementation of an xcpP/xcpQ mutant can be obtained with the gene couple xphA/xqhA. The XphA and XqhA proteins (the P(A)Q(A) subunit) could thus form, together with XcpR-Z, a functional hybrid T2SS. A two-dimensional polyacrylamide gel electrophoresis analysis showed that except for the aminopeptidase PaAP, for which secretion is not restored by the P(A)Q(A) subunit in the xcpP/xcpQ deletion mutant, each major Xcp-dependent exoprotein is secreted by the new hybrid machinery. Our work supports the idea that components of the GspC/GspD families, such as XphA/XqhA or XcpP/XcpQ, are assembled as a specific tandem within the T2SS. Each of these pairs may thus confer a different level of secretion specificity, as is the case with respect to PaAP. Finally, using a chromosomal xphA-lacZ fusion, we showed that the xphA-xqhA genes are transcribed from an early stage of bacterial growth. We thus suggest that the P(A)Q(A) subunit might be involved in the secretion process at a different growth stage than XcpP/XcpQ. PMID- 17351036 TI - A novel fur- and iron-regulated small RNA, NrrF, is required for indirect fur mediated regulation of the sdhA and sdhC genes in Neisseria meningitidis. AB - Iron is both essential for bacterial growth and toxic at higher concentrations; thus, iron homeostasis is tightly regulated. In Neisseria meningitidis the majority of iron-responsive gene regulation is mediated by the ferric uptake regulator protein (Fur), a protein classically defined as a transcriptional repressor. Recently, however, microarray studies have identified a number of genes in N. meningitidis that are iron and Fur activated, demonstrating a new role for Fur as a transcriptional activator. Since Fur has been shown to indirectly activate gene transcription through the repression of small regulatory RNA molecules in other organisms, we hypothesized that a similar mechanism could account for Fur-dependent, iron-activated gene transcription in N. meningitidis. In this study, we used a bioinformatics approach to screen for the presence of Fur-regulated small RNA molecules in N. meningitidis MC58. This screen identified one small RNA, herein named NrrF (for neisserial regulatory RNA responsive to iron [Fe]), which was demonstrated to be both iron responsive and Fur regulated and which has a well-conserved orthologue in N. gonorrhoeae. In addition, this screen identified a number of other likely, novel small RNA transcripts. Lastly, we utilized a new bioinformatics approach to predict regulatory targets of the NrrF small RNA. This analysis led to the identification of the sdhA and sdhC genes, which were subsequently demonstrated to be under NrrF regulation in an nrrF mutant. This study is the first report of small RNAs in N. meningitidis and the first to use a bioinformatics approach to identify, a priori, regulatory targets of a small RNA. PMID- 17351037 TI - Regulation of hydrogen peroxide-dependent gene expression in Rhodobacter sphaeroides: regulatory functions of OxyR. AB - Genome-wide transcriptome profiling was used to reveal hydrogen peroxide (H(2)O(2))-dependent regulatory mechanisms in the facultatively photosynthetic bacterium Rhodobacter sphaeroides. In this study we focused on the role of the OxyR protein, a known regulator of the H(2)O(2) response in bacteria. The transcriptome profiles of R. sphaeroides wild-type and oxyR mutant strains that were exposed to 1 mM H(2)O(2) for 7 min or were not exposed to H(2)O(2) were analyzed. Three classes of OxyR-dependent genes were identified based on their expression patterns in the wild type of oxyR mutant strains with differing predicted roles of oxidized and reduced OxyR as activators of transcription. DNA binding studies revealed that OxyR binds upstream of class I genes, which are induced by H(2)O(2) and exhibit similar basal levels of expression in the wild type and oxyR mutant strains. The effect of OxyR on class II genes, which are also induced by H(2)O(2) but exhibit significantly lower basal levels of expression in the wild-type strain than in the mutant, is indirect. Interestingly, reduced OxyR also activates expression of few genes (class III). The role of reduced OxyR as an activator is shown for the first time. Our data reveal that the OxyR-mediated response is fast and transient. In addition, we found that additional regulatory pathways are involved in the H(2)O(2) response. PMID- 17351038 TI - Error-prone DNA repair system in enteroaggregative Escherichia coli identified by subtractive hybridization. AB - Enteroaggregative Escherichia coli (EAEC) are etiologic agents of diarrhea. The EAEC category is heterogeneous, but most in-depth experimentation has focused on prototypical strain, 042. We hypothesized that 60A, another EAEC strain, might posses virulence or fitness genes that 042 does not have. Through subtractive hybridization we identified 60A-specific sequences, including loci present in other E. coli and phage DNA. One locus thus identified was impB, a LexA repressed error-prone DNA repair gene that has been identified in plasmids from other enteric organisms and which we detected in 21 of 34 EAEC strains. An isogenic 60A impB mutant showed decreased survival and mutagenesis after exposure to UV, as well as bile salt exposure, compared to the wild-type strain, and these phenotypes could be complemented in trans. The EAEC strain 60A imp operon differs structurally from previously described homologs. A cryptic gene, impC, present in other imp operons, is absent from 60A. In addition, transcription of impAB in strain 60A occurs from a promoter that is dissimilar to the previously described impC promoter but is still triggered by UV-mediated damage. In strain 60A the impAB and the aggregative adherence fimbriae I (AAF/I)-encoding genes are on the same large plasmid, and the 60A version of the operon is predominantly seen in AAF/I-positive EAEC. Supplementary imp SOS-inducible error-prone repair systems are common among EAEC even though they are absent in prototypical strain 042. PMID- 17351039 TI - Identification of critical residues in the propeptide of LasA protease of Pseudomonas aeruginosa involved in the formation of a stable mature protease. AB - LasA protease is a 20-kDa elastolytic and staphylolytic enzyme secreted by Pseudomonas aeruginosa. LasA is synthesized as a preproenzyme that undergoes proteolysis to remove a 22-kDa amino-terminal propeptide. Like the propeptides of other bacterial proteases, the LasA propeptide may act as an intramolecular chaperone that correctly folds the mature domain into an active protease. To locate regions of functional importance within proLasA, linker-scanning insertional mutagenesis was employed using a plasmid containing lasA as the target. Among the 5 missense insertions found in the mature domain of proLasA, all abolished enzymatic activity but not secretion. In general, the propeptide domain was more tolerant to insertions. However, insertions within a 9-amino-acid region in the propeptide caused dramatic reductions in LasA enzymatic activity. All mutant proLasA proteins were still secreted, but extracellular stability was low due to clustered insertions within the propeptide. The codons of 16 residues within and surrounding the identified 9-amino-acid region were subjected to site directed mutagenesis. Among the alanine substitutions in the propeptide that had a major effect on extracellular LasA activity, two (L92A and W95A) resulted in highly unstable proteins that were susceptible to proteolytic degradation and three (H94A, I101A, and N102A) were moderately unstable and allowed the production of a LasA protein with low enzymatic activity. These data suggest that these clustered residues in the propeptide may play an important role in promoting the correct protein conformation of the mature LasA protease domain. PMID- 17351040 TI - Biosynthesis of isoprenoid wax ester in Marinobacter hydrocarbonoclasticus DSM 8798: identification and characterization of isoprenoid coenzyme A synthetase and wax ester synthases. AB - Marinobacter hydrocarbonoclasticus DSM 8798 has been reported to synthesize isoprenoid wax ester storage compounds when grown on phytol as the sole carbon source under limiting nitrogen and/or phosphorous conditions. We hypothesized that isoprenoid wax ester synthesis involves (i) activation of an isoprenoid fatty acid by a coenzyme A (CoA) synthetase and (ii) ester bond formation between an isoprenoid alcohol and isoprenoyl-CoA catalyzed, most likely, by an isoprenoid wax ester synthase similar to an acyl wax ester synthase, wax ester synthase/diacylglycerol acyltransferase (WS/DGAT), recently described from Acinetobacter sp. strain ADP1. We used the recently released rough draft genome sequence of a closely related strain, M. aquaeolei VT8, to search for WS/DGAT and acyl-CoA synthetase candidate genes. The sequence information from putative WS/DGAT and acyl-CoA synthetase genes identified in this strain was used to clone homologues from the isoprenoid wax ester synthesizing Marinobacter strain. The activities of the recombinant enzymes were characterized, and two new isoprenoid wax ester synthases capable of synthesizing isoprenoid ester and acyl/isoprenoid hybrid ester in vitro were identified along with an isoprenoid-specific CoA synthetase. One of the Marinobacter wax ester synthases displays several orders of magnitude higher activity toward acyl substrates than any previously characterized acyl-WS and may reflect adaptations to available carbon sources in their environments. PMID- 17351041 TI - Integrated response to inducers by communication between a catabolic pathway and its regulatory system. AB - Efficient gene regulation of metabolic pathways implies that the profile of molecules inducing the pathway matches that of the molecules that are metabolized. Gratuitous induction, a well-known phenomenon in catabolic pathways, is the consequence of differences in the substrate and inducer profiles. This phenomenon is particularly evident in pathways for biodegradation of organic contaminants that can be induced by a variety of molecules similar to the real substrates. Analysis of the regulation of tetralin biodegradation genes in mutant strains with mutations that affect each component of the initial dioxygenase enzymatic complex indicated that the response of the regulatory system to potential inducers is altered differently depending on the mutated component. Based on the expression phenotypes of a number of single or double mutants, we propose a model that represents an unprecedented way of communication between a catabolic pathway and its regulatory system to prevent efficient induction by a molecule that is not a real substrate. This communication allows a better fit of the substrate and inducer profiles, thus minimizing gratuitous induction, without a requirement for optimal coevolution to match the specificity of catabolic enzymes and their regulatory systems. Modulation of the regulatory system in this way not only provides a more appropriate response to potential inducers recognized by the regulatory system but also may properly adjust the levels of gene expression to the substrate availability. PMID- 17351042 TI - Molecular genetics and genomic analysis of scytonemin biosynthesis in Nostoc punctiforme ATCC 29133. AB - The indole-alkaloid scytonemin is the most common and widespread sunscreen among cyanobacteria. Previous research has focused on its nature, distribution, ecology, physiology, and biochemistry, but its molecular genetics have not been explored. In this study, a scytonemin-deficient mutant of the cyanobacterium Nostoc punctiforme ATCC 29133 was obtained by random transposon insertion into open reading frame NpR1273. The absence of scytonemin under conditions of induction by UV irradiation was the single phenotypic difference detected in a comparative analysis of the wild type and the mutant. A cause-effect relationship between the phenotype and the mutation in NpR1273 was demonstrated by constructing a second scytoneminless mutant through directed mutagenesis of that gene. The genomic region flanking the mutation revealed an 18-gene cluster (NpR1276 to NpR1259). Four putative genes in the cluster, NpR1274 to NpR1271, with no previously known functions, are likely to be involved in the assembly of scytonemin. Also in this cluster, there is a redundant set of genes coding for shikimic acid and aromatic amino acid biosynthesis enzymes, leading to the production of tryptophan and tyrosine, which are likely to be biosynthetic precursors of the sunscreen. PMID- 17351043 TI - Differential Bvg phase-dependent regulation and combinatorial role in pathogenesis of two Bordetella paralogs, BipA and BcfA. AB - To successfully colonize their mammalian hosts, many bacteria produce multiple virulence factors that play essential roles in disease processes and pathogenesis. Some of these molecules are adhesins that allow efficient attachment to host cells, a prerequisite for successful host colonization. Bordetella spp. express a number of proteins which either play a direct role in attachment to the respiratory epithelia or exhibit similarity to known bacterial adhesins. One such recently identified protein is BipA. Despite the similarity of BipA to intimins and invasins, deletion of this protein from B. bronchiseptica did not result in any significant defect in respiratory tract colonization. In this study, we identified an open reading frame in B. bronchiseptica, designated bcfA (encoding BcfA [bordetella colonization factor A]), that is similar to bipA. In contrast to the maximal expression of bipA in the Bvg intermediate (Bvg(i)) phase, bcfA is expressed at high levels in both the Bvg(+) and Bvg(i) phases. We show here that BvgA and phosphorylated BvgA bind differentially to the bcfA promoter region. Utilizing immunoblot assays, we found that BcfA is localized to the outer membrane and that it is expressed during animal infection. While deletion of either bipA or bcfA did not significantly affect respiratory tract colonization, concomitant deletion of both genes resulted in a defect in colonization of the rat trachea. Our results indicate that the two paralogous proteins have a combinatorial role in mediating efficient respiratory tract colonization. PMID- 17351044 TI - Expression analysis of multiple dnaK genes in the cyanobacterium Synechococcus elongatus PCC 7942. AB - We analyzed the stress responses of three dnaK homologues (dnaK1, dnaK2, and dnaK3) in the cyanobacterium Synechococcus elongatus PCC 7942. A reporter assay showed that under stress conditions the expression of only the dnaK2 gene was induced, suggesting a functional assignment of these homologues. RNA blot hybridization indicated a typical stress response of dnaK2 to heat and high-light stress. Primer extension mapping showed that dnaK2 was transcribed from similar sites under various stress conditions. Although no known sequence motif was detected in the upstream region, a 20-bp sequence element was highly conserved in dnaK2; it was essential not only for the stress induction but also for the basal expression of dnaK2. The ubiquitous upstream localization of this element in each heat shock gene suggests its important role in the cyanobacterial stress response. PMID- 17351045 TI - MarT activates expression of the MisL autotransporter protein of Salmonella enterica serotype Typhimurium. AB - MisL is a Salmonella enterica serotype Typhimurium fibronectin binding protein whose expression is induced during infection of mice. T-POP transposon mutagenesis identified marT as a positive regulatory element controlling expression of a misL::lacZYA transcriptional fusion. Gel shift analysis identified MarT as a transcriptional activator of the misL promoter. PMID- 17351046 TI - The Escherichia coli regulator of sigma 70 protein, Rsd, can up-regulate some stress-dependent promoters by sequestering sigma 70. AB - The Escherichia coli Rsd protein forms complexes with the RNA polymerase sigma(70) factor, but its biological role is not understood. Transcriptome analysis shows that overexpression of Rsd causes increased expression from some promoters whose expression depends on the alternative sigma(38) factor, and this was confirmed by experiments with lac fusions at selected promoters. The LP18 substitution in Rsd increases the Rsd-dependent stimulation of these promoter-lac fusions. Analysis with a bacterial two-hybrid system shows that the LP18 substitution in Rsd increases its interaction with sigma(70). Our experiments support a model in which the role of Rsd is primarily to sequester sigma(70), thereby increasing the levels of RNA polymerase containing the alternative sigma(38) factor. PMID- 17351047 TI - Defining genomic islands and uropathogen-specific genes in uropathogenic Escherichia coli. AB - Uropathogenic Escherichia coli (UPEC) strains are responsible for the majority of uncomplicated urinary tract infections, which can present clinically as cystitis or pyelonephritis. UPEC strain CFT073, isolated from the blood of a patient with acute pyelonephritis, was most cytotoxic and most virulent in mice among our strain collection. Based on the genome sequence of CFT073, microarrays were utilized in comparative genomic hybridization (CGH) analysis of a panel of uropathogenic and fecal/commensal E. coli isolates. Genomic DNA from seven UPEC (three pyelonephritis and four cystitis) isolates and three fecal/commensal strains, including K-12 MG1655, was hybridized to the CFT073 microarray. The CFT073 genome contains 5,379 genes; CGH analysis revealed that 2,820 (52.4%) of these genes were common to all 11 E. coli strains, yet only 173 UPEC-specific genes were found by CGH to be present in all UPEC strains but in none of the fecal/commensal strains. When the sequences of three additional sequenced UPEC strains (UTI89, 536, and F11) and a commensal strain (HS) were added to the analysis, 131 genes present in all UPEC strains but in no fecal/commensal strains were identified. Seven previously unrecognized genomic islands (>30 kb) were delineated by CGH in addition to the three known pathogenicity islands. These genomic islands comprise 672 kb of the 5,231-kb (12.8%) genome, demonstrating the importance of horizontal transfer for UPEC and the mosaic structure of the genome. UPEC strains contain a greater number of iron acquisition systems than do fecal/commensal strains, which is reflective of the adaptation to the iron limiting urinary tract environment. Each strain displayed distinct differences in the number and type of known virulence factors. The large number of hypothetical genes in the CFT073 genome, especially those shown to be UPEC specific, strongly suggests that many urovirulence factors remain uncharacterized. PMID- 17351048 TI - Nitric oxide synthase-dependent nitric oxide production is associated with salt tolerance in Arabidopsis. AB - Nitric oxide (NO) has emerged as a key molecule involved in many physiological processes in plants. To characterize roles of NO in tolerance of Arabidopsis (Arabidopsis thaliana) to salt stress, effect of NaCl on Arabidopsis wild-type and mutant (Atnoa1) plants with an impaired in vivo NO synthase (NOS) activity and a reduced endogenous NO level was investigated. Atnoa1 mutant plants displayed a greater Na+ to K+ ratio in shoots than wild-type plants due to enhanced accumulation of Na+ and reduced accumulation of K+ when exposed to NaCl. Germination of Atnoa1 seeds was more sensitive to NaCl than that of wild-type seeds, and wild-type plants exhibited higher survival rates than Atnoa1 plants when grown under salt stress. Atnoa1 plants had higher levels of hydrogen peroxide than wild-type plants under both control and salt stress, suggesting that Atnoa1 is more vulnerable to salt and oxidative stress than wild-type plants. Treatments of wild-type plants with NOS inhibitor and NO scavenger reduced endogenous NO levels and enhanced NaCl-induced increase in Na+ to K+ ratio. Exposure of wild-type plants to NaCl inhibited NOS activity and reduced quantity of NOA1 protein, leading to a decrease in endogenous NO levels measured by NO-specific fluorescent probe. Treatment of Atnoa1 plants with NO donor sodium nitroprusside attenuated the NaCl-induced increase in Na+ to K+ ratio. Therefore, these findings provide direct evidence to support that disruption of NOS dependent NO production is associated with salt tolerance in Arabidopsis. PMID- 17351050 TI - The MI-1-mediated pest resistance requires Hsp90 and Sgt1. AB - The tomato (Solanum lycopersicum) Mi-1 gene encodes a protein with putative coiled-coil nucleotide-binding site and leucine-rich repeat motifs. Mi-1 confers resistance to root-knot nematodes (Meloidogyne spp.), potato aphids (Macrosiphum euphorbiae), and sweet potato whitefly (Bemisia tabaci). To identify genes required in the Mi-1-mediated resistance to nematodes and aphids, we used tobacco rattle virus (TRV)-based virus-induced gene silencing (VIGS) to repress candidate genes and assay for nematode and aphid resistance. We targeted Sgt1 (suppressor of G-two allele of Skp1), Rar1 (required for Mla12 resistance), and Hsp90 (heat shock protein 90), which are known to participate early in resistance gene signaling pathways. Two Arabidopsis (Arabidopsis thaliana) Sgt1 genes exist and one has been implicated in disease resistance. Thus far the sequence of only one Sgt1 ortholog is known in tomato. To design gene-specific VIGS constructs, we cloned a second tomato Sgt1 gene, Sgt1-2. The gene-specific VIGS construct TRV SlSgt1-1 resulted in lethality, while silencing Sgt1-2 using TRV-SlSgt1-2 did not result in lethal phenotype. Aphid and root-knot nematode assays of Sgt1-2 silenced plants indicated no role for Sgt1-2 in Mi-1-mediated resistance. A Nicotiana benthamiana Sgt1 VIGS construct silencing both Sgt1-1 and Sgt1-2 yielded live plants and identified a role for Sgt1 in Mi-1-mediated aphid resistance. Silencing of Rar1 did not affect Mi-1-mediated nematode and aphid resistance and demonstrated that Rar1 is not required for Mi-1 resistance. Silencing Hsp90-1 resulted in attenuation of Mi-1-mediated aphid and nematode resistance and indicated a role for Hsp90-1. The requirement for Sgt1 and Hsp90-1 in Mi-1-mediated resistance provides further evidence for common components in early resistance gene defense signaling against diverse pathogens and pests. PMID- 17351051 TI - The FRD3-mediated efflux of citrate into the root vasculature is necessary for efficient iron translocation. AB - Iron, despite being an essential micronutrient, becomes toxic if present at high levels. As a result, plants possess carefully regulated mechanisms to acquire iron from the soil. The ferric reductase defective3 (frd3) mutant of Arabidopsis (Arabidopsis thaliana) is chlorotic and exhibits constitutive expression of its iron uptake responses. Consequently, frd3 mutants overaccumulate iron; yet, paradoxically, the frd3 phenotypes are due to a reduction in the amount of iron present inside frd3 leaf cells. The FRD3 protein belongs to the multidrug and toxin efflux family, members of which are known to export low-M(r) organic molecules. We therefore hypothesized that FRD3 loads an iron chelator necessary for the correct distribution of iron throughout the plant into the xylem. One such potential chelator is citrate. Xylem exudate from frd3 plants contains significantly less citrate and iron than the exudate from wild-type plants. Additionally, supplementation of growth media with citrate rescues the frd3 phenotypes. The ectopic expression of FRD3-GFP results in enhanced tolerance to aluminum in Arabidopsis roots, a hallmark of organic acid exudation. Consistent with this result, approximately 3 times more citrate was detected in root exudate from plants ectopically expressing FRD3-GFP. Finally, heterologous studies in Xenopus laevis oocytes reveal that FRD3 mediates the transport of citrate. These results all strongly support the hypothesis that FRD3 effluxes citrate into the root vasculature, a process important for the translocation of iron to the leaves, as well as confirm previous reports suggesting that iron moves through the xylem as a ferric-citrate complex. Our results provide additional answers to long-standing questions about iron chelation in the vasculature and organic acid transport. PMID- 17351049 TI - Sampling the Arabidopsis transcriptome with massively parallel pyrosequencing. AB - Massively parallel sequencing of DNA by pyrosequencing technology offers much higher throughput and lower cost than conventional Sanger sequencing. Although extensively used already for sequencing of genomes, relatively few applications of massively parallel pyrosequencing to transcriptome analysis have been reported. To test the ability of this technology to provide unbiased representation of transcripts, we analyzed mRNA from Arabidopsis (Arabidopsis thaliana) seedlings. Two sequencing runs yielded 541,852 expressed sequence tags (ESTs) after quality control. Mapping of the ESTs to the Arabidopsis genome and to The Arabidopsis Information Resource 7.0 cDNA models indicated: (1) massively parallel pyrosequencing detected transcription of 17,449 gene loci providing very deep coverage of the transcriptome. Performing a second sequencing run only increased the number of genes identified by 10%, but increased the overall sequence coverage by 50%. (2) Mapping of the ESTs to their predicted full-length transcripts indicated that all regions of the transcript were well represented regardless of transcript length or expression level. Furthermore, short, medium, and long transcripts were equally represented. (3) Over 16,000 of the ESTs that mapped to the genome were not represented in the existing dbEST database. In some cases, the ESTs provide the first experimental evidence for transcripts derived from predicted genes, and, for at least 60 locations in the genome, pyrosequencing identified likely protein-coding sequences that are not now annotated as genes. Together, the results indicate massively parallel pyrosequencing provides novel information helpful to improve the annotation of the Arabidopsis genome. Furthermore, the unbiased representation of transcripts will be particularly useful for gene discovery and gene expression analysis of nonmodel plants with less complete genomic information. EST sequence accession numbers in GenBank are EH 795234 through EH 995233 and EL 000001 through EL 341852. PMID- 17351053 TI - A WUSCHEL-LIKE HOMEOBOX gene represses a YABBY gene expression required for rice leaf development. AB - YABBY and WUSCHEL-LIKE HOMEOBOX (WOX) genes have been shown to play important roles in lateral organ formation and meristem function. Here, we report the characterization of functional relationship between rice (Oryza sativa) YAB3 and WOX3 in rice leaf development. Rice YAB3 is closely related to maize (Zea mays) ZmYAB14 and Arabidopsis (Arabidopsis thaliana) FILAMENTOUS FLOWER (FIL), whereas rice WOX3 is highly conserved with maize narrow sheath1 (NS1) and NS2 and Arabidopsis PRESSED FLOWER (PRS). In situ hybridization experiments revealed that the expression of both genes was excluded from the shoot apical meristem, but the transcripts were detected in leaf primordia, young leaves, and reproductive organs without any polar distribution. The function of the two genes was studied by both overexpression and RNA interference (RNAi) in transgenic rice. YAB3 RNAi induced twisted and knotted leaves lacking specialized structures such as ligule and auricles, while no phenotypic change was observed in YAB3 overexpression plants, suggesting that rice YAB3 may be required for leaf cell growth and differentiation. Overexpression of WOX3 repressed YAB3 and showed a YAB3 RNAi phenotype. The expression of class I KNOTTED-LIKE HOMEOBOX (KNOX) genes was ectopically induced in leaves of YAB3 RNAi or WOX3 overexpression plants. Data from inducible WOX3 expression and DNA-protein interaction assays suggested that WOX3 acted as a transcriptional repressor of YAB3. These data reveal a regulatory network involving YAB3, WOX3, and KNOX genes required for rice leaf development. PMID- 17351055 TI - A novel bioinformatics approach identifies candidate genes for the synthesis and feruloylation of arabinoxylan. AB - Arabinoxylans (AXs) are major components of graminaceous plant cell walls, including those in the grain and straw of economically important cereals. Despite some recent advances in identifying the genes encoding biosynthetic enzymes for a number of other plant cell wall polysaccharides, the genes encoding enzymes of the final stages of AX synthesis have not been identified. We have therefore adopted a novel bioinformatics approach based on estimation of differential expression of orthologous genes between taxonomic divisions of species. Over 3 million public domain cereal and dicot expressed sequence tags were mapped onto the complete sets of rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana) genes, respectively. It was assumed that genes in cereals involved in AX biosynthesis would be expressed at high levels and that their orthologs in dicotyledonous plants would be expressed at much lower levels. Considering all rice genes encoding putative glycosyl transferases (GTs) predicted to be integral membrane proteins, genes in the GT43, GT47, and GT61 families emerged as much the strongest candidates. When the search was widened to all other rice or Arabidopsis genes predicted to encode integral membrane proteins, cereal genes in Pfam family PF02458 emerged as candidates for the feruloylation of AX. Our analysis, known activities, and recent findings elsewhere are most consistent with genes in the GT43 families encoding beta-1,4-xylan synthases, genes in the GT47 family encoding xylan alpha-1,2- or alpha-1,3-arabinosyl transferases, and genes in the GT61 family encoding feruloyl-AX beta-1,2-xylosyl transferases. PMID- 17351054 TI - Magnaporthe grisea infection triggers RNA variation and antisense transcript expression in rice. AB - Rice blast disease, caused by the fungal pathogen Magnaporthe grisea, is an excellent model system to study plant-fungal interactions and host defense responses. In this study, comprehensive analysis of the rice (Oryza sativa) transcriptome after M. grisea infection was conducted using robust-long serial analysis of gene expression. A total of 83,382 distinct 21-bp robust-long serial analysis of gene expression tags were identified from 627,262 individual tags isolated from the resistant (R), susceptible (S), and control (C) libraries. Sequence analysis revealed that the tags in the R and S libraries had a significant reduced matching rate to the rice genomic and expressed sequences in comparison to the C library. The high level of one-nucleotide mismatches of the R and S library tags was due to nucleotide conversions. The A-to-G and U-to-C nucleotide conversions were the most predominant types, which were induced in the M. grisea-infected plants. Reverse transcription-polymerase chain reaction analysis showed that expression of the adenine deaminase and cytidine deaminase genes was highly induced after inoculation. In addition, many antisense transcripts were induced in infected plants and expression of four antisense transcripts was confirmed by strand-specific reverse transcription-polymerase chain reaction. These results demonstrate that there is a series of dynamic and complex transcript modifications and changes in the rice transcriptome at the M. grisea early infection stages. PMID- 17351056 TI - E2F regulates FASCIATA1, a chromatin assembly gene whose loss switches on the endocycle and activates gene expression by changing the epigenetic status. AB - Maintenance of genome integrity depends on histone chaperone-mediated chromatin reorganization. DNA replication-associated nucleosome deposition relies on chromatin assembly factor-1 (CAF-1). Depletion of CAF-1 in human cells leads to cell death, whereas in Arabidopsis (Arabidopsis thaliana), where it is involved in heterochromatin compaction and homologous recombination, plants are viable. The mechanism that makes the lack of CAF-1 activity compatible with development is not known. Here, we show that the FASCIATA1 (FAS1) gene, which encodes the CAF 1 large subunit, is a target of E2F transcription factors. Mutational studies demonstrate that one of the two E2F binding sites in its promoter has an activator role, whereas the other has a repressor function. Loss of FAS1 results in reduced type A cyclin-dependent kinase activity, inhibits mitotic progression, and promotes a precocious and systemic switch to the endocycle program. Selective up-regulation of the expression of a subset of genes, including those involved in activation of the G2 DNA damage checkpoint, also occurs upon FAS1 loss. This activation is not the result of a global change in chromatin structure, but depends on selective epigenetic changes in histone acetylation and methylation within a small region in their promoters. This suggests that correct chromatin assembly during the S-phase is required to prevent unscheduled changes in the epigenetic marks of target genes. Interestingly, activation of the endocycle switch as well as introduction of activating histone marks in the same set of G2 checkpoint genes are detected upon treatment of wild-type plants with DNA damaging treatments. Our results are consistent with a model in which defects in chromatin assembly during the S-phase and DNA damage signaling share part of a pathway, which ultimately leads to mitotic arrest and triggers the endocycle program. Together, this might be a bypass mechanism that makes development compatible with cell division arrest induced by DNA damage stress. PMID- 17351052 TI - Nitric oxide and cGMP signaling in calcium-dependent development of cell polarity in Ceratopteris richardii. AB - Single-celled spores of the fern Ceratopteris richardii undergo gravity-directed cell polarity development that is driven by polar calcium currents. Here we present results that establish a role for nitric oxide (NO)/cGMP signaling in transducing the stimulus of gravity to directed polarization of the spores. Application of specific NO donors and scavengers inhibited the calcium-dependent gravity response in a dose-dependent manner. The effects of NO donor exposure were antagonized by application of NO scavenger compounds. Similarly, the guanylate cyclase inhibitors 6-anilino-5,8-quinolinedione and 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin, and the phosphodiesterase inhibitor Viagra, which modulate NO-dependent cGMP levels in the cells, disrupted gravity-directed cell polarity in a dose-dependent manner. Viagra effects were antagonized by application of NO scavengers, consistent with the postulate that NO and cGMP are linked in the signaling pathway. To identify other components of the signaling system we analyzed gene expression changes induced by Viagra treatment using microarrays and quantitative real-time reverse transcription-polymerase chain reaction. Preliminary microarray analysis revealed several genes whose expression was significantly altered by Viagra treatment. Three of these genes had strong sequence similarity to key signal transduction or stress response genes and quantitative real-time reverse transcription-polymerase chain reaction was used to more rigorously quantify the effects of Viagra on their expression in spores and to test how closely these effects could be mimicked by treatment with dibutyryl cGMP. Taken together our results implicate NO and cGMP as downstream effectors that help link the gravity stimulus to polarized growth in C. richardii spores. Sequence data from this article can be found in the GenBank/EMBL data libraries under accession numbers BE 640669 to BE 643506, BQ 086920 to BQ 087668, and CV 734654 to CV 736151. PMID- 17351059 TI - The response to recruitment worsens with progression of lung injury and fibrin accumulation in a mouse model of acid aspiration. AB - Reopening the injured lung with deep inflation (DI) and positive end-expiratory pressure (PEEP) likely depends on the duration and severity of acute lung injury (ALI), key features of which include increased alveolar permeability and fibrin accumulation. We hypothesized that the response to DI and PEEP would worsen as ALI evolves and that this would correspond with increasing accumulation of alveolar fibrin. C57BL/6 mice were anesthetized and aspirated 75 microl of HCl (pH 1.8) or buffered normal saline. Subgroups were reanesthetized 4, 14, 24, and 48 h later. Following DI, tissue damping (G) and elastance (H) were measured periodically at PEEP of 1, 3, and 6 cmH(2)O, and air within the lung (thoracic gas volume) was quantified by microcomputed tomography. Following DI, G and H increased with time during progressive lung derecruitment, the latter confirmed by microcomputed tomography. The rise in H was greater in acid-injured mice than in controls (P < 0.05) and also increased from 4 to 48 h after acid aspiration, reflecting progressively worsening injury. The rise in H was reduced by PEEP, but this effect was significantly blunted by 48 h (P < 0.05), also confirmed by thoracic gas volume. Lung permeability and alveolar fibrin also increased over the 48-h study period, accompanied by increasing levels and transcription of the fibrinolysis inhibitor plasminogen activator inhibitor-1. Lung injury worsens progressively in mice during the 48 h following acid aspiration. This injury manifests as progressively increasing alveolar instability, likely due to surfactant dysfunction caused by increasing levels of alveolar protein and fibrin. PMID- 17351058 TI - Successful gene tagging in lettuce using the Tnt1 retrotransposon from tobacco. AB - The tobacco (Nicotiana tabacum) element Tnt1 is one of the few identified active retrotransposons in plants. These elements possess unique properties that make them ideal genetic tools for gene tagging. Here, we demonstrate the feasibility of gene tagging using the retrotransposon Tnt1 in lettuce (Lactuca sativa), which is the largest genome tested for retrotransposon mutagenesis so far. Of 10 different transgenic bushes carrying a complete Tnt1 containing T-DNA, eight contained multiple transposed copies of Tnt1. The number of transposed copies of the element per plant was particularly high, the smallest number being 28. Tnt1 transposition in lettuce can be induced by a very simple in vitro culture protocol. Tnt1 insertions were stable in the progeny of the primary transformants and could be segregated genetically. Characterization of the sequences flanking some insertion sites revealed that Tnt1 often inserted into genes. The progeny of some primary transformants showed phenotypic alterations due to recessive mutations. One of these mutations was due to Tnt1 insertion in the gibberellin 3beta-hydroxylase gene. Taken together, these results indicate that Tnt1 is a powerful tool for insertion mutagenesis especially in plants with a large genome. PMID- 17351057 TI - A genomic approach to suberin biosynthesis and cork differentiation. AB - Cork (phellem) is a multilayered dead tissue protecting plant mature stems and roots and plant healing tissues from water loss and injuries. Cork cells are made impervious by the deposition of suberin onto cell walls. Although suberin deposition and cork formation are essential for survival of land plants, molecular studies have rarely been conducted on this tissue. Here, we address this question by combining suppression subtractive hybridization together with cDNA microarrays, using as a model the external bark of the cork tree (Quercus suber), from which bottle cork is obtained. A suppression subtractive hybridization library from cork tree bark was prepared containing 236 independent sequences; 69% showed significant homology to database sequences and they corresponded to 135 unique genes. Out of these genes, 43.5% were classified as the main pathways needed for cork biosynthesis. Furthermore, 19% could be related to regulatory functions. To identify genes more specifically required for suberin biosynthesis, cork expressed sequence tags were printed on a microarray and subsequently used to compare cork (phellem) to a non-suberin-producing tissue such as wood (xylem). Based on the results, a list of candidate genes relevant for cork was obtained. This list includes genes for the synthesis, transport, and polymerization of suberin monomers such as components of the fatty acid elongase complexes, ATP-binding cassette transporters, and acyltransferases, among others. Moreover, a number of regulatory genes induced in cork have been identified, including MYB, No-Apical-Meristem, and WRKY transcription factors with putative functions in meristem identity and cork differentiation. PMID- 17351060 TI - Cigarette smoke extract-induced suppression of caspase-3-like activity impairs human neutrophil phagocytosis. AB - Neutrophils are the primary inflammatory cell in smokers' lungs, but little is known about the ability of cigarette smoke to modulate neutrophil function. Neutrophils undergo caspase-3-dependent spontaneous, as well as phagocytosis induced, apoptosis. This study investigated the ability of cigarette smoke extract (CSE) to alter neutrophil caspase-3 activity, apoptosis, and phagocytosis. CSE treatment resulted in a dramatic suppression of neutrophil caspase-3-like activity, which correlated with reduced cleavage of glutamate-L cysteine ligase catalytic subunit, a known target of active caspase-3. CSE did not affect procaspase-3 processing to its active fragment, suggesting a direct effect of CSE on active caspase-3. Consistent with this, CSE inhibited active recombinant caspase-3 activity, which was abolished by dithiothreitol, suggesting a redox-sensitive mechanism. CSE-induced suppression of caspase-3 activity did not alter spontaneous apoptosis but did impair phagocytic activity. Since CSE treatment resulted in profound suppression of caspase-3 activity but did not alter apoptosis, the possibility of a threshold level of caspase-3 activity was investigated. CSE reduced caspase-3 activity in a concentration-dependent manner. Despite near complete suppression of caspase-3 activity, spontaneous apoptosis was not altered. Conversely, treatment with the pan-caspase inhibitor, Z-Val-Ala Asp-fluoromethylketone, reduced spontaneous apoptosis. These data demonstrate that CSE does not suppress caspase-3 activity below a threshold level to prevent spontaneous apoptosis, but the level of inhibition is sufficient to impair neutrophil phagocytic activity. These divergent functions of caspase-3 may contribute to the persistence of neutrophils in the lungs of smokers, as well as be a factor in their higher incidence of community-acquired pneumonia. PMID- 17351062 TI - Heparan sulfates mediate pressure-induced increase in lung endothelial hydraulic conductivity via nitric oxide/reactive oxygen species. AB - We investigated the nonlinear dynamics of the pressure vs. hydraulic conductivity (L(p)) relationship in lung microvascular endothelial cells and demonstrate that heparan sulfates, an important component of the endothelial glycocalyx, participate in pressure-sensitive mechanotransduction that results in barrier dysfunction. The pressure vs. L(p) relationship was complex, possessing both time and pressure-dependent components. Pretreatment of lung capillary endothelial cells with heparanase III completely abolished the pressure-induced increase in L(p). This extends our (7) previous observation regarding heparan sulfates as mechanotransducers for shear stress. Inhibition of nitric oxide (NO) synthase with L-NAME (N(G)-nitro-L-arginine methyl ester HCl) and intracellular scavenging of reactive oxygen species (ROS) by TBAP [tetrakis-(4-benzoic acid) porphorin] significantly attenuated the pressure-induced L(p) response. Intracellular NO/ROS were visualized using the fluorescent dye, 2'7'-dichlorofluorescein diacetate (DCFA), and cells demonstrated a pressure-induced increase in intracellular fluorescence. Heparanase pretreatment significantly reduced the pressure-induced increase in intracellular fluorescence, suggesting that cell-surface heparan sulfates directly participate in mechanotransduction that results in NO/ROS production and increased permeability. This is the first report to demonstrate a role for heparan sulfates in pressure-mediated mechanotransduction and barrier regulation. These observations may have important clinical implications during conditions where pulmonary microvascular pressure is elevated. PMID- 17351061 TI - Physiological and biochemical markers of alveolar epithelial barrier dysfunction in perfused human lungs. AB - To study air space fluid clearance (AFC) under conditions that resemble the clinical setting of pulmonary edema in patients, we developed a new perfused human lung preparation. We measured AFC in 20 human lungs rejected for transplantation and determined the contribution of AFC to lung fluid balance. AFC was then compared with air space and perfusate levels of a biological marker of epithelial injury. The majority of human lungs rejected for transplant had intact basal (75%) and beta(2)-adrenergic agonist-stimulated (70%) AFC. For lungs with both basal and stimulated AFC, the basal AFC rate was 19 +/- 10%/h, and the beta(2)-adrenergic-stimulated AFC rate was 43 +/- 13%/h. Higher rates of AFC were associated with less lung weight gain (Pearson coefficient -0.90, P < 0.0001). Air space and perfusate levels of the type I pneumocyte marker receptor for advanced glycation end products (RAGE) were threefold and sixfold higher, respectively, in lungs without basal AFC compared with lungs with AFC (P < 0.05). These data show that preserved AFC is a critical determinant of favorable lung fluid balance in the perfused human lung, raising the possibility that beta(2) agonist therapy to increase edema fluid clearance may be of value for patients with acute lung injury and pulmonary edema. Also, although additional studies are needed, a biological marker of alveolar epithelial injury may be useful clinically in predicting preserved AFC. PMID- 17351064 TI - Oxygen delivery by blood determines the maximal VO2 and work rate during whole body exercise in humans: in silico studies. AB - It has been proposed by Saltin (J Exp Biol 115: 345-354, 1985) that oxygen delivery by blood is limiting for maximal work and oxygen consumption in humans during whole body exercise but not during single-muscle exercise. To test this prediction quantitatively, we developed a static (steady-state) computer model of oxygen transport to and within human skeletal muscle during single-muscle (quadriceps) exercise and whole body (cycling) exercise. The main system fluxes, namely cardiac output and oxygen consumption by muscle, are described as a function of the "primary" parameter: work rate. The model is broadly validated by comparison of computer simulations with various experimental data. In silico studies show that, when all other parameters and system properties are kept constant, an increase in the working muscle mass from 2.5 kg (single quadriceps) to 15 kg (two legs) causes, at some critical work intensity, a drop in oxygen concentration in muscle cells to (very near) zero, and therefore oxygen supply by blood limits maximal oxygen consumption and oxidative ATP production. Therefore, the maximal oxygen consumption per muscle mass is significantly higher during single-muscle exercise than during whole body exercise. The effect is brought about by a distribution of a limited amount of oxygen transported by blood in a greater working muscle mass during whole body exercise. PMID- 17351063 TI - Dose-dependent recruitment of CD25+ and CD26+ T cells in a novel F344 rat model of asthma. AB - The ovalbumin (OVA)-induced airway inflammation in rats is a commonly used model to explore the pathobiology of asthma. However, its susceptibility varies greatly between rat strains, and presently Brown Norway (BN) rats are preferentially used. Since recruitment of T cells to the lungs depends on the CD26 (dipeptidyl peptidase IV, DPPIV) expression, Fischer 344 strain (F344) rats are a highly relevant rat strain, in particular because CD26-deficient substrains are available. To establish a F344 rat model of asthma, we challenged F344 rats using different doses of aerosolized antigen (0%, 1%, 2.5%, 5%, and 7.5% OVA) and compared these effects with intratracheal instillation of OVA (1.5 mg/0.3 ml). Asthmoid responsiveness was determined by analysis of early airway responsiveness (EAR), antigen-specific IgE levels, as well as airway inflammation including the composition of T cell subpopulations in the bronchoalveolar lavage (BAL) and lung tissue with special respect to the T cell activation markers CD25 and CD26. Even low allergen doses caused allergen-specific EAR and increases of antigen-specific IgE levels. However, EAR and IgE levels did not increase dose dependently. Higher concentrations of OVA led to a dose-dependent increase of several immunological markers of allergic asthma including an influx of eosinophils, T cells, and dendritic cells. Interestingly, a dose-dependent increase of CD4(+)/CD25(+)/CD26(+) T cells was found in the lungs. Summarizing, we established a novel F344 rat model of aerosolized OVA-induced asthma. Thereby, we found a dose-dependent recruitment of cellular markers of allergic asthma including the activated CD4(+)/CD25(+)/CD26(+) T cell subpopulation, which has not been described in asthma yet. PMID- 17351065 TI - Cardiovascular dysfunction in Zucker obese and Zucker diabetic fatty rats: role of hydronephrosis. AB - Recent studies in our laboratory using the Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rat models resulted in unexpectedly high mortality rates in all genotypes including healthy homozygous lean Zucker rats, possibly because of renal dysfunction. Therefore, we evaluated left ventricular (LV) and kidney morphology and function in young ZO, Zucker diabetic fatty obese (ZDFO), homozygous Zucker/ZDF lean (ZL), and Sprague-Dawley (SD) rats. Hydronephrosis was evident in ZL, ZO, and ZDFO but not SD kidneys. ZDFO rats exhibited impaired LV shortening and relaxation with increased arterial stiffness. LV wall thickness was lower and LV end-systolic wall stress was higher in ZDFO compared with SD rats. Plasma ANG II was lower in ZO and ZDFO rats, which may be a result of reduced renal parenchyma with hydronephrosis; norepinephrine was higher in ZDFO rats than SD controls. Covariate analysis indicated that LV end-systolic wall stress was associated with renal dysfunction. The presence of hydronephrosis and its association with LV dysfunction potentially limits the ZDF model for study of the effects of diabetes on renal and cardiovascular function. PMID- 17351067 TI - Differential regulation of L-type Ca2+ channels in cerebral and mesenteric arteries after simulated microgravity in rats and its intervention by standing. AB - This study was designed to clarify whether simulated microgravity can induce differential changes in the current and protein expression of the L-type Ca(2+) channel (Ca(L)) in cerebral and mesenteric arteries and whether these changes can be prevented by daily short-duration -G(x) exposure. Tail suspension [hindlimb unloading (HU)] for 3 and 28 days was used to simulate short- and medium-term microgravity-induced deconditioning effects. Standing (STD) for 1 h/day was used to provide -G(x) as a countermeasure. Whole cell patch-clamp experiments revealed an increase in current density of Ca(L) of vascular smooth muscle cells (VSMCs) isolated from cerebral arteries of rats subjected to HU and a decrease in VSMCs from mesenteric arteries. Western blot analysis revealed a significant increase and decrease of Ca(L) channel protein expression in cerebral and small mesenteric arterial VSMCs, respectively, only after 28 days of HU. STD for 1 h/day did not prevent the increase of Ca(L) current density in cerebral arterial VSMCs, but it prevented completely (within 3 days) and partially (28 days) the decrease of Ca(L) current density in small mesenteric arterial VSMCs. Consistent with the changes in Ca(L) current, STD for 1 h/day did not prevent the increase of Ca(L) expression in cerebrovascular myocytes but did prevent the reduction of Ca(L) expression in mesenteric arterial VSMCs subjected to 28 days of HU. These data indicate that simulated microgravity up- and downregulates the current and expression of Ca(L) in cerebral and hindquarter VSMCs, respectively. STD for 1 h/day differentially counteracted the changes of Ca(L) function and expression in cerebral and hindquarter arterial VSMCs of HU rats, suggesting the complexity of the underlying mechanisms in the effectiveness of intermittent artificial gravity for prevention of postflight cardiovascular deconditioning, which needs further clarification. PMID- 17351066 TI - Nongenomic, endothelium-independent effects of estrogen on human coronary smooth muscle are mediated by type I (neuronal) NOS and PI3-kinase-Akt signaling. AB - Sex steroids exert profound and controversial effects on cardiovascular function. For example, estrogens have been reported to either ameliorate or exacerbate coronary heart disease. Although estrogen dilates coronary arteries from a variety of species, the molecular basis for this acute, nongenomic effect is unclear. Moreover, we know very little of how estrogen affects human coronary artery smooth muscle cells (HCASMC). The purpose of this study was to elucidate nongenomic estrogen signal transduction in HCASMC. We have used tissue (arterial tension studies), cellular (single-channel patch clamp, fluorescence), and molecular (protein expression) techniques to now identify novel targets of estrogen action in HCASMC: type I (neuronal) nitric oxide synthase (nNOS) and phosphatidylinositol 3-kinase (PI3-kinase)Akt. 17beta-Estradiol (E(2)) increased NO-stimulated fluorescence in HCASMC, and cell-attached patch-clamp experiments revealed that stimulation of nNOS leads to increased activity of calcium activated potassium (BK(Ca)) channels in these cells. Furthermore, overexpression of nNOS protein in HCASMC greatly enhanced BK(Ca) channel activity. Immunoblot studies demonstrated that E(2) enhances Akt phosphorylation in HCASMC and that wortmannin, an inhibitor of PI3-kinase, attenuated E(2)-stimulated channel activity, NO production, Akt phosphorylation, and estrogen-stimulated coronary relaxation. These studies implicate the PI3-kinase/Akt signaling axis as an estrogen transduction component in vascular smooth muscle cells. We conclude, therefore, that estrogen opens BK(Ca) channels in HCASMC by stimulating nNOS via a transduction sequence involving PI3-kinase and Akt. These findings now provide a molecular mechanism that can explain the clinical observation that estrogen enhances coronary blood flow in patients with diseased or damaged coronary arteries. PMID- 17351068 TI - Protein kinase C isoform-dependent modulation of ATP-sensitive K+ channels in mitochondrial inner membrane. AB - The ATP-sensitive K(+) (K(ATP)) channels in both sarcolemmal (sarcK(ATP)) and mitochondrial inner membrane (mitoK(ATP)) are the critical mediators in cellular protection of ischemic preconditioning (IPC). Whereas cardiac sarcK(ATP) contains Kir6.2 and sulfonylurea receptor (SUR)2A, the molecular identity of mitoK(ATP) remains elusive. In the present study, we tested the hypothesis that protein kinase C (PKC) may promote import of Kir6.2-containing K(ATP) into mitochondria. Fluorescence imaging of isolated mitochondria from both rat adult cardiomyocytes and COS-7 cells expressing recombinant Kir6.2/SUR2A showed that Kir6.2-containing K(ATP) channels were localized in mitochondria and this mitochondrial localization was significantly increased by PKC activation with phorbol 12 myristate 13-acetate (PMA). Fluorescence resonance energy transfer microscopy further revealed that a significant number of Kir6.2-containing K(ATP) channels were localized in mitochondrial inner membrane after PKC activation. These results were supported by Western blotting showing that the Kir6.2 protein level in mitochondria from COS-7 cells transfected with Kir6.2/SUR2A was enhanced after PMA treatment and this increase was inhibited by the selective PKC inhibitor chelerythrine. Furthermore, functional analysis indicated that the number of functional K(ATP) channels in mitochondria was significantly increased by PMA, as shown by K(ATP)-dependent decrease in mitochondrial membrane potential in COS-7 cells transfected with Kir6.2/SUR2A but not empty vector. Importantly, PKC mediated increase in mitochondrial Kir6.2-containing K(ATP) channels was blocked by a selective PKCepsilon inhibitor peptide in both COS-7 cells and cardiomyocytes. We conclude that the K(ATP) channel pore-forming subunit Kir6.2 is indeed localized in mitochondria and that the Kir6.2 content in mitochondria is increased by activation of PKCepsilon. PKC isoform-regulated mitochondrial import of K(ATP) channels may have significant implication in cardioprotection of IPC. PMID- 17351069 TI - An analysis of the DOCA-salt model of hypertension in HO-1-/- mice and the Gunn rat. AB - Heme oxygenase-1 (HO-1) is induced in the vasculature in the DOCA-salt model of hypertension in rats. Whereas the HO system and its products may exert vasodilator effects, recent studies have suggested that the HO system may predispose to hypertension. The present study examined the effects of selected components of the HO system, specifically, the HO-1 isozyme and the product bilirubin in the DOCA-salt model of systemic hypertension; the experimental approach employed mutant rodent models, namely, the HO-1(-/-) mouse and the hyperbilirubinemic Gunn rat. DOCA-salt induced HO-1 protein in the aorta in HO 1(+/+) mice and provoked a significant rise in systolic arterial pressure in HO 1(-/-) mice but not in HO-1(+/+) mice; this effect could not be ascribed to impaired urinary sodium excretion or impaired glomerular filtration rate in the DOCA-salt-treated HO-1(-/-) mice. The administration of DOCA salt to uninephrectomized rats significantly increased systolic arterial pressure in wild type rats, an effect that was attenuated in the mutant Gunn rat; this reduction in systemic hypertension in the DOCA-salt-treated Gunn rat was not due to a greater induction of HO-1 in the vasculature or to a more avid urinary sodium excretion. DOCA-salt impaired endothelium-dependent and endothelium-independent vasorelaxation in wild-type rats but not in Gunn rats; prior exposure to bilirubin repaired the defect in endothelium-dependent vasorelaxation in aortic rings in DOCA-salt-treated rats. DOCA salt stimulated vascular production of superoxide anion in wild-type but not in Gunn rats. We suggest that HO-1 and the product bilirubin may exert a countervailing effect in the DOCA-salt model of systemic hypertension. PMID- 17351070 TI - Mitochondrial Ca2+-activated K+ channels more efficiently reduce mitochondrial Ca2+ overload in rat ventricular myocytes. AB - We investigated the role of the mitochondrial ATP-sensitive K(+) (K(ATP)) channel, the mitochondrial big-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, and the mitochondrial permeability transition pore (MPTP) in the ouabain induced increase of mitochondrial Ca(2+) in native rat ventricular myocytes by loading cells with rhod 2-AM. To overload mitochondrial Ca(2+), we pretreated cells with ouabain before applying mitochondrial K(ATP) or BK(Ca) channel and/or MPTP opener. Ouabain (1 mM) increased the rhod 2-sensitive fluorescence intensity (160 +/- 5.0% of control), which was dramatically decreased to the control level on application of diazoxide and NS-1619 in a dose-dependent manner (half inhibition concentrations of 78.3 and 7.78 muM for diazoxide and NS-1619, respectively). This effect was reversed by selective inhibition of the mitochondrial K(ATP) channel by 5-hydroxydecanoate, the mitochondrial BK(Ca) channel by paxilline, and the MPTP by cyclosporin A. Although diazoxide did not efficiently reduce mitochondrial Ca(2+) during prolonged exposure to ouabain, NS 1619 reduced mitochondrial Ca(2+). These results suggest that although mitochondrial BK(Ca) and K(ATP) channels contribute to reduction of ouabain induced mitochondrial Ca(2+) overload, activation of the mitochondrial BK(Ca) channel more efficiently reduces ouabain-induced mitochondrial Ca(2+) overload in our experimental model. PMID- 17351071 TI - Effects of posture on peripheral vascular responses to lower body positive pressure. AB - We tested the hypothesis that peripheral vascular responses (in the lower and upper limbs) to application of lower body positive pressure (LBPP) are dependent on the posture of the subjects. We measured heart rate, stroke volume, mean arterial pressure, leg and forearm blood flow (using the Doppler ultrasound technique), and leg (LVC) and forearm (FVC) vascular conductance in 11 subjects (9 men, 2 women) without and with LBPP (25 and 50 mmHg) in supine and upright postures. Mean arterial pressure increased in proportion to increases in LBPP and was greater in supine than in upright subjects. Heart rate was unchanged when LBPP was applied to supine subjects but was reduced in upright ones. Leg blood flow and LVC were both reduced by LBPP in supine subjects [LVC: 4.8 (SD 4.0), 3.6 (SD 3.5), and 1.4 (SD 1.8) ml.min(-1).mmHg(-1) before LBPP and during 25 and 50 mmHg LBPP, respectively; P < 0.05] but were increased in upright ones [LVC: 2.0 (SD 1.2), 3.4 (SD 3.4), and 3.0 (SD 2.0) ml.min(-1).mmHg(-1), respectively; P < 0.05]. Forearm blood flow and FVC both declined when LBPP was applied to supine subjects [FVC: 1.3 (SD 0.6), 1.0 (SD 0.4), and 0.9 (SD 0.6) ml. min(-1).mmHg(-1), respectively; P < 0.05] but remained unchanged in upright ones [FVC: 0.7 (SD 0.4), 0.7 (SD 0.4), and 0.6 (SD 0.5) ml.min(-1).mmHg(-1), respectively]. Together, these findings indicate that the leg vascular response to application of LBPP is posture dependent and that the response differs in the lower and upper limbs when subjects assume an upright posture. PMID- 17351072 TI - Estrogen-TNF interactions and vascular inflammation. PMID- 17351073 TI - Hypertrophic and dilated cardiomyopathy mutations differentially affect the molecular force generation of mouse alpha-cardiac myosin in the laser trap assay. AB - Point mutations in cardiac myosin, the heart's molecular motor, produce distinct clinical phenotypes: hypertrophic (HCM) and dilated (DCM) cardiomyopathy. Do mutations alter myosin's molecular mechanics in a manner that is predictive of the clinical outcome? We have directly characterized the maximal force-generating capacity (F(max)) of two HCM (R403Q, R453C) and two DCM (S532P, F764L) mutant myosins isolated from homozygous mouse models using a novel load-clamped laser trap assay. F(max) was 50% (R403Q) and 80% (R453C) greater for the HCM mutants compared with the wild type, whereas F(max) was severely depressed for one of the DCM mutants (65% S532P). Although F(max) was normal for the F764L DCM mutant, its actin-activated ATPase activity and actin filament velocity (V(actin)) in a motility assay were significantly reduced (Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner DA, Mende U, Lohse MJ, Warshaw D, Seidman CE, Seidman JG. Proc Natl Acad Sci USA 103: 14525-14530, 2006.). These F(max) data combined with previous V(actin) measurements suggest that HCM and DCM result from alterations to one or more of myosin's fundamental mechanical properties, with HCM-causing mutations leading to enhanced but DCM-causing mutations leading to depressed function. These mutation-specific changes in mechanical properties must initiate distinct signaling cascades that ultimately lead to the disparate phenotypic responses observed in HCM and DCM. PMID- 17351074 TI - Forebrain regions associated with postexercise differences in autonomic and cardiovascular function during baroreceptor unloading. AB - The cortical regions representing peripheral autonomic reactions in humans are poorly understood. This study examined whether changes in forebrain activity were associated with the altered physiological responses to lower body negative pressure (LBNP) following a single bout of dynamic exercise (POST-EX). We hypothesized that, compared with the nonexercised condition (NO-EX), POST-EX would elicit greater reductions in stroke volume (SV) and larger increases in heart rate (HR) and muscle sympathetic nerve activity (MSNA) during LBNP (5, 15, and 35 mmHg). Forebrain neural activity (n = 11) was measured using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. HR, SV, arterial blood pressure (ABP), and MSNA were collected separately. Compared with NO-EX, baseline ABP was reduced, whereas HR and total vascular conductance (TVC) were elevated in POST-EX (P < 0.05). In both conditions, 5 mmHg LBNP did not elicit a change (from baseline) in any physiological parameter. Compared with NO-EX, 35 mmHg LBNP-mediated decreases in SV and TVC produced greater increases in HR and MSNA during POST-EX (P < 0.05). The right posterior insula and dorsal anterior cingulate cortex demonstrated a larger decrease in BOLD at 5 mmHg LBNP but greater BOLD increase at 15 and 35 mmHg LBNP POST-EX vs. NO-EX (P < 0.005). Conversely, the thalamus and ventral medial prefrontal cortex displayed the opposite BOLD activity pattern (i.e., larger increase at 5 mmHg LBNP but greater decrease at 15 and 35 mmHg LBNP POST-EX vs. NO-EX). Our findings suggest that discrete forebrain regions may be involved with the generation of baroreflex mediated sympathetic and cardiovascular responses elicited by moderate LBNP. PMID- 17351076 TI - Diversity of Ca2+-induced morphology revealed by morphological phenotyping of Ca2+-sensitive mutants of Saccharomyces cerevisiae. AB - Yeast cell morphology can be treated as a quantitative trait using the image processing software CalMorph. In the present study, we investigated Ca(2+) induced morphological changes in Ca(2+)-sensitive (cls) mutants of Saccharomyces cerevisiae, based on the discovery that the characteristic Ca(2+)-induced morphological changes in the Ca(2+)-sensitive mutant zds1 reflect changes in the Ca(2+) signaling-mediated cell cycle control pathway. By applying hierarchical cluster analysis to the quantitative morphological data of 58 cls mutants, 31 of these mutants were classified into seven classes based on morphological similarities. The patterns of morphological change induced by Ca(2+) in one class differed from those of another class. Based on the results obtained using versatile methods for phenotypic analysis, we conclude that a high concentration of Ca(2+) exerts a wide variety of effects on yeast and that there are multiple Ca(2+)-regulatory pathways that are distinct from the Zds1p-related pathway. PMID- 17351075 TI - Multiple basic helix-loop-helix proteins regulate expression of the ENO1 gene of Saccharomyces cerevisiae. AB - The basic helix-loop-helix (bHLH) eukaryotic transcription factors have the ability to form multiple dimer combinations. This property, together with limited DNA-binding specificity for the E box (CANNTG), makes them ideally suited for combinatorial control of gene expression. We tested the ability of all nine Saccharomyces cerevisiae bHLH proteins to regulate the enolase-encoding gene ENO1. ENO1 was known to be activated by the bHLH protein Sgc1p. Here we show that expression of an ENO1-lacZ reporter was also regulated by the other eight bHLH proteins, namely, Ino2p, Ino4p, Cbf1p, Rtg1p, Rtg3p, Pho4p, Hms1p, and Ygr290wp. ENO1-lacZ expression was also repressed by growth in inositol-choline-containing medium. Epistatic analysis and chromatin immunoprecipitation experiments showed that regulation by Sgc1p, Ino2p, Ino4p, and Cbf1p and repression by inositol choline required three distal E boxes, E1, E2, and E3. The pattern of bHLH binding to the three E boxes and experiments with two dominant-negative mutant alleles of INO4 and INO2 support the model that bHLH dimer selection affects ENO1 lacZ expression. These results support the general model that bHLH proteins can coordinate different biological pathways via multiple mechanisms. PMID- 17351077 TI - The WW domain protein PRO40 is required for fungal fertility and associates with Woronin bodies. AB - Fruiting body formation in ascomycetes is a highly complex process that is under polygenic control and is a fundamental part of the fungal sexual life cycle. However, the molecular determinants regulating this cellular process are largely unknown. Here we show that the sterile pro40 mutant is defective in a 120-kDa WW domain protein that plays a pivotal role in fruiting body maturation of the homothallic ascomycete Sordaria macrospora. Although WW domains occur in many eukaryotic proteins, homologs of PRO40 are present only in filamentous ascomycetes. Complementation analysis with different pro40 mutant strains, using full-sized or truncated versions of the wild-type pro40 gene, revealed that the C terminus of PRO40 is crucial for restoring the fertile phenotype. Using differential centrifugation and protease protection assays, we determined that a PRO40-FLAG fusion protein is located within organelles. Further microscopic investigations of fusion proteins with DsRed or green fluorescent protein polypeptides showed a colocalization of PRO40 with HEX-1, a Woronin body-specific protein. However, the integrity of Woronin bodies is not affected in mutant strains of S. macrospora and Neurospora crassa, as shown by fluorescence microscopy, sedimentation, and immunoblot analyses. We discuss the function of PRO40 in fruiting body formation. PMID- 17351078 TI - The pathogenic fungus Cryptococcus neoformans expresses two functional GDP mannose transporters with distinct expression patterns and roles in capsule synthesis. AB - Cryptococcus neoformans is a fungal pathogen that is responsible for life threatening disease, particularly in the context of compromised immunity. This organism makes extensive use of mannose in constructing its cell wall, glycoproteins, and glycolipids. Mannose also comprises up to two-thirds of the main cryptococcal virulence factor, a polysaccharide capsule that surrounds the cell. The glycosyltransfer reactions that generate cellular carbohydrate structures usually require activated donors such as nucleotide sugars. GDP mannose, the mannose donor, is produced in the cytosol by the sequential actions of phosphomannose isomerase, phosphomannomutase, and GDP-mannose pyrophosphorylase. However, most mannose-containing glycoconjugates are synthesized within intracellular organelles. This topological separation necessitates a specific transport mechanism to move this key precursor across biological membranes to the appropriate site for biosynthetic reactions. We have discovered two GDP-mannose transporters in C. neoformans, in contrast to the single such protein reported previously for other fungi. Biochemical studies of each protein expressed in Saccharomyces cerevisiae show that both are functional, with similar kinetics and substrate specificities. Microarray experiments indicate that the two proteins Gmt1 and Gmt2 are transcribed with distinct patterns of expression in response to variations in growth conditions. Additionally, deletion of the GMT1 gene yields cells with small capsules and a defect in capsule induction, while deletion of GMT2 does not alter the capsule. We suggest that C. neoformans produces two GDP-mannose transporters to satisfy its enormous need for mannose utilization in glycan synthesis. Furthermore, we propose that the two proteins have distinct biological roles. This is supported by the different expression patterns of GMT1 and GMT2 in response to environmental stimuli and the dissimilar phenotypes that result when each gene is deleted. PMID- 17351080 TI - Clinical measurement of pharyngeal surface electromyography: exploratory research. AB - BACKGROUND: Dysphagia diagnosis is limited by our inability to evaluate the underlying neuromuscular pathology of swallowing. A novel approach using pharyngeal surface electromyography (PsEMG) has been reported in the literature. OBJECTIVE: Three exploratory projects were undertaken to provide data toward the validation of PsEMG as a clinical measure of pharyngeal physiology. The first evaluates laterality of electrode placement in the pharynx. The second and third evaluate PsEMG using a circumferential and unidirectional electrode, respectively, during swallowing maneuvers. METHODS: In experiment 1, a catheter housing 3 manometric sensors and 1 bipolar PsEMG electrode was randomly inserted in each nares of 10 participants. Moving jaw radiographs were taken, and the PsEMG electrode was measured in millimeters from midline. In experiments 2 and 3, the catheter was placed in 22 and 40 research participants, respectively. Waveform characteristics were collected during swallowing maneuvers. The 2 experiments differed by type of electrode (circumferential, unidirectional) and swallowing maneuver (noneffortful and effortful swallow; noneffortful, effortful, and tongue-hold swallow). RESULTS: Midline electrode placement occurred on 20% of trials with deviation of up to 14.7 mm on all other trials. Maneuver-specific differences in amplitude were not detected with PsEMG; unacceptable levels of intrasubject and intersubject variability were identified. Temporal relationships of PsEMG and pharyngeal manometric pressure appeared appropriate. The unidirectional electrode revealed a unique bimodal PsEMG pattern that may reflect sequential contraction of muscles of the posterior pharyngeal wall. CONCLUSIONS: The current PsEMG design and procedures do not validly measure pharyngeal muscle activity. Recommendations for improved methods are provided. PMID- 17351079 TI - Candida albicans Rho-type GTPase-encoding genes required for polarized cell growth and cell separation. AB - Rho proteins are essential regulators of morphogenesis in eukaryotic cells. In this report, we investigate the role of two previously uncharacterized Rho proteins, encoded by the Candida albicans RHO3 (CaRHO3) and CaCRL1/CaRHO4 genes. The CaRHO3 gene was found to contain one intron. Promoter shutdown experiments using a MET3 promoter-controlled RHO3 revealed a strong cell polarity defect and a partially depolarized actin cytoskeleton. Hyphal growth after promoter shutdown was abolished in rho3 mutants even in the presence of a constitutively active ras1(G13V) allele, and existing germ tubes became swollen. Deletion of C. albicans RHO4 indicated that it is a nonessential gene and that rho4 mutants were phenotypically different from rho3. Two distinct phenotypes of rho4 cells were elongated cell morphology and an unexpected cell separation defect generating chains of cells. Colony morphology of crl1/rho4 resulted in a growth-dependent smooth (long cell cycle length) or wrinkled (short cell cycle length) phenotype. This phenotype was additionally dependent on the rho4 cell separation defect and was also found in a Cacht3 chitinase mutant that shows a strong cytokinesis defect. The overexpression of the endoglucanase encoding the ENG1 gene, but not CHT3, suppressed the cell separation defect of crl1/rho4 but could not suppress the cell elongation phenotype. C. albicans Crl1/Rho4 and Bnr1 both localize to septal sites in yeast and hyphal cells but not to the hyphal tip. Deletion of RHO4 and BNR1 produced similar morphological phenotypes. Based on the localization of Rho4 and on the rho4 mutant phenotype, we propose a model in which Rho4p may function as a regulator of cell polarity, breaking the initial axis of polarity found during early bud growth to promote the construction of a septum. PMID- 17351081 TI - Impaired discrimination of surface friction contributes to pinch grip deficit after stroke. AB - BACKGROUND: Impaired sensation and force production could both contribute to handgrip limitation after stroke. Clinically, training is usually directed to motor impairment rather than sensory impairment despite the prevalence of sensory deficit and the importance of sensory input for grip control. OBJECTIVE: The aim of this study was to investigate if sensory deficits contribute to pinch grip dysfunction beyond that attributable to motor deficits poststroke. METHODS: The study enlisted 45 stroke participants and 45 healthy controls matched for age, gender, and hand dominance. Ability to differentiate surface friction (Friction Discrimination Test [FDT]), match object weight (Weight Matching Test [WMT]), produce grip force to track a visual target (Visually Guided Pinch Test [VGPT]), and perform a Pinch-Grip Lift-and-Hold Test (PGLHT) was quantified relative to normative performance, as defined by matched controls. The relationship between sensory ability (FDT, WMT) and altered PGLHT performance adjusted for motor ability (VGPT) after stroke was then examined using multivariate regression. RESULTS: Deficits in FDT, WMT, and VGPT ability were present in at least half of the stroke sample and were largely independent across the variables. Poorer friction discrimination was significantly associated with longer latencies of grip-lift (r = .34; P = .03) and grip force dysregulation (r= .34; P= .03) after the impact of VGPT was statistically removed from PGLHT ability. However, performance on WMT did not relate to either PGLHT deficit. CONCLUSION: The findings indicate that impaired friction discrimination ability contributes to altered timing and force adjustment during PGLHT poststroke. PMID- 17351082 TI - Establishing the minimal clinically important difference of the Barthel Index in stroke patients. AB - BACKGROUND: The interpretation of the change scores of the Barthel Index (BI) in follow-up or outcome studies has been hampered by the fact that its minimal clinically important difference (MCID) has not been determined. OBJECTIVE: This article was written to establish the MCID of the BI in stroke patients. METHODS: Both anchor-based and distribution-based methods were used to establish the MCID. In the anchor-based method, 43 stroke inpatients participated in a follow-up study designed to determine the MCID of the BI using patients' global ratings of the activities of daily living function on a 15-point Likert-type scale. The mean change scores on the 20-point scale of the BI of the MCID group, based on the patients' ratings on the Likert-type scale, served as the first estimate of the MCID. In the distribution-based method, 56 chronic stroke patients participated in the test-retest reliability study to determine the MCID of the BI. One standard error of measurement (SEM) served as the second estimate for the MCID. The larger MCID value of the 2 estimates was chosen as the MCID of the BI. RESULTS: In the anchor-based study, there were 20 patients in the MCID group, with a mean change score of 1.85 points (ie, the first MCID estimate). In the distribution-based study, the SEM based on test-retest agreement was 1.45 points (ie, the second MCID estimate). The MCID of the BI in stroke patients was estimated to be 1.85 points. CONCLUSION: The authors' results, within the limitations of their design, suggest that if the mean BI change score within a stroke group has reached 1.85 points in a study, the change score on the BI can be perceived by patients as important and beyond measurement error (ie, such a change score is clinically important). PMID- 17351083 TI - Comparison of finger tracking versus simple movement training via telerehabilitation to alter hand function and cortical reorganization after stroke. AB - OBJECTIVE: To compare 2 telerehabilitation training strategies, repetitive tracking movements versus repetitive simple movements, to promote brain reorganization and recovery of hand function. METHODS: Twenty subjects with chronic stroke and 10 degrees of voluntary finger extension were randomly assigned to receive 1800 telerehabilitation trials over 2 weeks of either computerized tracking training (track group) with the affected finger and wrist involving temporospatial processing to achieve accuracy or movement training (move group) with no attention to accuracy. Following movement training, the move group crossed over to receive an additional 2 weeks of tracking training. Behavioral changes were measured with the Box and Block test, Jebsen Taylor test, and finger range of motion, along with a finger-tracking activation paradigm during fMRI. RESULTS: The track group showed significant improvement in all 4 behavioral tests; the move group improved in the Box and Block and Jebsen Taylor tests. The improvement for the track group in the Box and Block and Jebsen Taylor tests did not surpass that for the move group. A consistent group pattern of brain reorganization was not evident. The move group, after crossing over, did not show further significant improvements. CONCLUSION: Telerehabilitation may be effective in improving performance in subjects with chronic stroke. Tracking training with reinforcement to enhance learning, however, did not produce a clear advantage over the same amount of practice of random movements. Two weeks of training may be insufficient to demonstrate a behavioral advantage and associated brain reorganization. PMID- 17351084 TI - Impaired short-term motor learning in multiple sclerosis: evidence from virtual reality. AB - OBJECTIVE: Virtual reality (VR) has been proposed as a potentially useful tool for motor assessment and rehabilitation. The objective of this study was to investigate the usefulness of VR in the assessment of short-term motor learning in multiple sclerosis (MS). METHODS: Twelve right-handed MS patients and 12 control individuals performed a motor-tracking task with their right upper limb, following the trajectory of an object projected on a screen along with online visual feedback on hand position from a sensor on the index finger. A pretraining test (3 trials), a training phase (12 trials), and a posttraining test (3 trials) were administered. Distances between performed and required trajectory were computed. RESULTS: Both groups performed worse in depth planes compared to the frontal (x,z) plane (P < .006). MS patients performed worse than control individuals in the frontal plane at both evaluations (P < .015), whereas they had lower percent posttraining improvement in the depth planes only (P = .03). CONCLUSIONS: The authors' VR system detected impaired motor learning in MS patients, especially for task features requiring a complex integration of sensory information (movement in the depth planes). These findings stress the need for careful customization of rehabilitation strategies, which must take into account the patients' motor, sensory, and cognitive limitations. PMID- 17351085 TI - Expiratory muscle strength training: speech production outcomes in patients with multiple sclerosis. AB - PURPOSE: This study investigated the effect of expiratory muscle strength training (EMST) on voice production, dysarthria, and voice-related quality-of life issues in persons with multiple sclerosis (PwMS). It was hypothesized that PwMS would have improved voice production and reduced voice-related quality-of life issues following EMST. PARTICIPANTS AND METHODS: Seventeen participants with MS and 14 healthy (H) controls completed 8 weeks of EMST, followed by 4 weeks of no training. Analyzed outcomes as a function of EMST were maximal expiratory pressure (MEP), sustained vowel prolongation (SVP), words per minute (WPM) measured from connected speech, and quality-of-life indices related to the presence of the dysarthria and dysphonia. RESULTS: PwMS had lower MEPs, shorter SVP, and less WPM than the controls prior to training. Following EMST, both groups had significant improvement in MEPs that stayed above baseline after training halted. EMST did not improve voice production or voice-related quality of life for PwMS. CONCLUSION: Respiratory muscle weakness is present in PwMS having mild- to moderate-level disability. EMST improved expiratory muscle strength but did not statistically change objective and subjective components of voice/speech production in PwMS. PMID- 17351086 TI - VEGF-C is associated with lymphatic status and invasion in oral cancer. AB - BACKGROUND: Nodal metastasis is a major prognostic indicator for oral squamous cell carcinoma (OSCC) progression. Recently, it has been revealed that lymphangiogenic growth factor VEGF-C and its receptor Flt-4 play an important role for invasion and metastasis in cancer cells. AIM: To examine VEGF-C expression and its correlation with lymphatic status, including the number of lymph vessels and lymphatic invasion, tumour invasion and metastasis in OSCC. METHODS: Intratumoural and peritumoural lymphatic vessels were examined using D2 40 in 54 OSCC cases and correlated with VEGF-C expression and clinicopathological findings. The histological pattern of invasion and pathological findings were compared. RESULTS: High expression of VEGF-C was frequently observed in OSCC and was associated with increased number of lymph vessels and lymphatic invasion. VEGF-C was well correlated with invasion pattern and metastasis. CONCLUSIONS: Results suggest that VEGF-C may play an important role for lymphangiogenesis and invasion in the metastatic process and can be a strong predicting factor for metastasis of OSCC. PMID- 17351087 TI - The microbial community structure in petroleum-contaminated sediments corresponds to geophysical signatures. AB - The interdependence between geoelectrical signatures at underground petroleum plumes and the structures of subsurface microbial communities was investigated. For sediments contaminated with light non-aqueous-phase liquids, anomalous high conductivity values have been observed. Vertical changes in the geoelectrical properties of the sediments were concomitant with significant changes in the microbial community structures as determined by the construction and evaluation of 16S rRNA gene libraries. DNA sequencing of clones from four 16S rRNA gene libraries from different depths of a contaminated field site and two libraries from an uncontaminated background site revealed spatial heterogeneity in the microbial community structures. Correspondence analysis showed that the presence of distinct microbial populations, including the various hydrocarbon-degrading, syntrophic, sulfate-reducing, and dissimilatory-iron-reducing populations, was a contributing factor to the elevated geoelectrical measurements. Thus, through their growth and metabolic activities, microbial populations that have adapted to the use of petroleum as a carbon source can strongly influence their geophysical surroundings. Since changes in the geophysical properties of contaminated sediments parallel changes in the microbial community compositions, it is suggested that geoelectrical measurements can be a cost-efficient tool to guide microbiological sampling for microbial ecology studies during the monitoring of natural or engineered bioremediation processes. PMID- 17351088 TI - Adherence of enterohemorrhagic Escherichia coli O157, O26, and O111 strains to bovine intestinal explants ex vivo. AB - We used bovine intestinal organ culture to study infection by enterohemorrhagic Escherichia coli serogroups O157, O26, and O111. We show colonization and attaching and effacing lesion formation on explants derived from the ileum, colon, and rectum. Intimin and Tir were detected at the sites of adherent bacteria; Tir was essential for colonization. PMID- 17351089 TI - Improved luciferase tagging system for Listeria monocytogenes allows real-time monitoring in vivo and in vitro. AB - An improved system for luciferase tagging Listeria monocytogenes was developed by constructing a highly active, constitutive promoter. This construct gave 100-fold higher activity in broth than any native promoter tested and allowed for imaging of lux-tagged L. monocytogenes in food products, during murine infections, and in tumor targeting studies. PMID- 17351090 TI - Characterization of a latent virus-like infection of symbiotic zooxanthellae. AB - A latent virus-like agent, which we designated zooxanthella filamentous virus 1 (ZFV1), was isolated from Symbiodinium sp. strain CCMP 2465 and characterized. Transmission electron microscopy and analytical flow cytometry revealed the presence of a new group of distinctive filamentous virus-like particles after exposure of the zooxanthellae to UV light. Examination of thin sections of the zooxanthellae revealed the formation and proliferation of filamentous virus-like particles in the UV-induced cells. Assessment of Symbiodinium sp. cultures was used here as a model to show the effects of UV irradiance and induction of potential latent viruses. The unique host-virus system described here provides insight into the role of latent infections in zooxanthellae through environmentally regulated viral induction mechanisms. PMID- 17351091 TI - Microbial reductive dechlorination of aroclor 1260 in Baltimore harbor sediment microcosms is catalyzed by three phylotypes within the phylum Chloroflexi. AB - The specific dechlorination pathways for Aroclor 1260 were determined in Baltimore Harbor sediment microcosms developed with the 11 most predominant congeners from this commercial mixture and their resulting dechlorination intermediates. Most of the polychlorinated biphenyl (PCB) congeners were dechlorinated in the meta position, and the major products were tetrachlorobiphenyls with unflanked chlorines. Using PCR primers specific for the 16S rRNA genes of known PCB-dehalogenating bacteria, we detected three phylotypes within the microbial community that had the capability to dechlorinate PCB congeners present in Aroclor 1260 and identified their selective activities. Phylotype DEH10, which has a high level of sequence identity to Dehalococcoides spp., removed the double-flanked chlorine in 234-substituted congeners and exhibited a preference for para-flanked meta-chlorines when no double-flanked chlorines were available. Phylotype SF1 had similarity to the o-17/DF-1 group of PCB-dechlorinating bacteria. Phylotype SF1 dechlorinated all of the 2345 substituted congeners, mostly in the double-flanked meta position and 2356-, 236 , and 235-substituted congeners in the ortho-flanked meta position, with a few exceptions. A phylotype with 100% sequence identity to PCB-dechlorinating bacterium o-17 was responsible for an ortho and a double-flanked meta dechlorination reaction. Most of the dechlorination pathways supported the growth of all three phylotypes based on competitive PCR enumeration assays, which indicates that PCB-impacted environments have the potential to sustain populations of these PCB-dechlorinating microorganisms. The results demonstrate that the variation in dechlorination patterns of congener mixtures typically observed at different PCB impacted sites can potentially be mediated by the synergistic activities of relatively few dechlorinating species. PMID- 17351092 TI - Adopting selected hydrogen bonding and ionic interactions from Aspergillus fumigatus phytase structure improves the thermostability of Aspergillus niger PhyA phytase. AB - Although it has been widely used as a feed supplement to reduce manure phosphorus pollution of swine and poultry, Aspergillus niger PhyA phytase is unable to withstand heat inactivation during feed pelleting. Crystal structure comparisons with its close homolog, the thermostable Aspergillus fumigatus phytase (Afp), suggest associations of thermostability with several key residues (E35, S42, R168, and R248) that form a hydrogen bond network in the E35-to-S42 region and ionic interactions between R168 and D161 and between R248 and D244. In this study, loss-of-function mutations (E35A, R168A, and R248A) were introduced singularly or in combination into seven mutants of Afp. All seven mutants displayed decreases in thermostability, with the highest loss (25% [P<0.05]) in the triple mutant (E35A R168A R248A). Subsequently, a set of corresponding substitutions were introduced into nine mutants of PhyA to strengthen the hydrogen bonding and ionic interactions. While four mutants showed improved thermostability, the best response came from the quadruple mutant (A58E P65S Q191R T271R), which retained 20% greater (P<0.05) activity after being heated at 80 degrees C for 10 min and had a 7 degrees C higher melting temperature than that of wild-type PhyA. This study demonstrates the functional importance of the hydrogen bond network and ionic interaction in supporting the high thermostability of Afp and the feasibility of adopting these structural units to improve the thermostability of a homologous PhyA phytase. PMID- 17351093 TI - Characterization of Fusarium oxysporum beta-1,6-galactanase, an enzyme that hydrolyzes larch wood arabinogalactan. AB - A type II arabinogalactan-degrading enzyme (FoGal1) was purified from Fusarium oxysporum 12S, and the corresponding cDNA was isolated. FoGal1 had high similarity to enzymes of glycoside hydrolase family 5. Treatment of larch wood arabinogalactan with the recombinant enzyme indicated that FoGal1 is a beta-1,6 galactanase that preferentially debranches beta-1,6-galactobiose from the substrate. PMID- 17351094 TI - Optimization of a 12-hour TaqMan PCR-based method for detection of Salmonella bacteria in meat. AB - We developed a 12-h Salmonella detection method, based on 8 h of preenrichment, followed by automated DNA extraction and a sensitive real-time PCR. The method was optimized to obtain the highest possible yield of cells and DNA. The growth of different Salmonella strains in various preenrichment media and the effects of adding growth-promoting and selective reagents were explored, taking into account their PCR compatibility. The effects of (i) analyzing larger volumes (1 to 5 ml) from preenriched samples and introducing wash steps prior to DNA extraction, (ii) regulating the amount of paramagnetic particles (increasing it from 60 to 90 microl) in the DNA extraction, (iii) eluting the DNA in reduced volumes (25 or 50 microl rather than 100 microl), and (iv) increasing the PCR template volume (from 5 to 20 microl) were investigated. After 8 h of preenrichment, buffered peptone water yielded the highest number of salmonellae. When analyzing minced meat samples, positive effects of increasing the initial sampling volume from 1 to 5 ml and increasing the amount of paramagnetic particles to 90 microl were observed. However, washing the pellet and eluting the DNA in reduced volumes (25 and 50 microl) had no positive effects and resulted in decreased reproducibility. Increasing the amount of PCR template DNA from 5 to 20 mul improved the threshold cycle value by approximately 2. The improved 12-h PCR method was successfully compared to a reference culture method with 100 minced meat and poultry samples, with a relative accuracy of 99%, a relative sensitivity of 98%, and a relative specificity of 100%. PMID- 17351095 TI - Second acyl homoserine lactone production system in the extreme acidophile Acidithiobacillus ferrooxidans. AB - The acidophilic proteobacterium Acidithiobacillus ferrooxidans is involved in the industrial biorecovery of copper. It is found in acidic environments in biofilms and is important in the biogeochemical cycling of metals and nutrients. Its genome contains a cluster of four genes, glyQ, glysS, gph, and act, that are predicted to encode the alpha and beta subunits of glycine tRNA synthetase, a phosphatase, and an acyltransferase, respectively (GenBank accession no. DQ149607). act, cloned and expressed in Escherichia coli, produces acyl homoserine lactones (AHLs) principally of chain length C14 according to gas chromatography and mass spectrometry measurements. The AHLs have biological activity as shown by in vivo studies using the reporter strain Sinorhizobium meliloti Rm41 SinI-. Reverse transcription-PCR (RT-PCR) experiments indicate that the four genes are expressed as a single transcript, demonstrating that they constitute an operon. According to semiquantitative RT-PCR results, act is expressed more highly when A. ferrooxidans is grown in medium containing iron than when it is grown in medium containing sulfur. Since AHLs are important intercellular signaling molecules used by many bacteria to monitor their population density in quorum-sensing control of gene expression, this result suggests that A. ferrooxidans has two quorum-sensing systems, one based on Act, as described herein, and the other based on a Lux-like quorum-sensing system, reported previously. The latter system was shown to be upregulated in A. ferrooxidans grown in sulfur medium, suggesting that the two quorum-sensing systems respond to different environmental signals that may be related to their abilities to colonize and use different solid sulfur- and iron-containing minerals. PMID- 17351096 TI - Structural analysis and characterization of lacticin Q, a novel bacteriocin belonging to a new family of unmodified bacteriocins of gram-positive bacteria. AB - Lactococcus lactis QU 5 isolated from corn produces a novel bacteriocin, termed lacticin Q. By acetone precipitation, cation-exchange chromatography, and reverse phase high-performance liquid chromatography, lacticin Q was purified from the culture supernatant of this organism, and its molecular mass was determined to be 5,926.50 Da by mass spectrometry. Subsequent analyses of amino acid and DNA sequences revealed that lacticin Q comprised 53 amino acid residues and that its N-terminal methionine residue was formylated. In contrast to most bacteriocins produced by gram-positive bacteria, lacticin Q had no N-terminal extensions such as leader or signal sequences. It showed 66% and 48% identity to AucA, a hypothetical protein from Corynebacterium jeikeium plasmid pA501, and aureocin A53, a bacteriocin from Staphylococcus aureus A53, respectively. The characteristics of lacticin Q were determined and compared to those of nisin A. Similar to nisin A, lacticin Q exhibited antibacterial activity against various gram-positive bacteria. Lacticin Q was very stable against heat treatment and changes in pH; in particular, it was stable at alkaline pH values, while nisin A was inactivated. Moreover, lacticin Q induced ATP efflux from a Listeria sp. strain in a shorter time and at a lower concentration than nisin A, indicating that the former affected indicator cells in a different manner from that of the latter. The results described here clarified the fact that lacticin Q belongs to a new family of class II bacteriocins and that it can be employed as an alternative to or in combination with nisin A. PMID- 17351097 TI - Flagellin diversity in Clostridium botulinum groups I and II: a new strategy for strain identification. AB - Strains of Clostridium botulinum are traditionally identified by botulinum neurotoxin type; however, identification of an additional target for typing would improve differentiation. Isolation of flagellar filaments and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that C. botulinum produced multiple flagellin proteins. Nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) analysis of in-gel tryptic digests identified peptides in all flagellin bands that matched two homologous tandem flagellin genes identified in the C. botulinum Hall A genome. Designated flaA1 and flaA2, these open reading frames encode the major structural flagellins of C. botulinum. Colony PCR and sequencing of flaA1/A2 variable regions classified 80 environmental and clinical strains into group I or group II and clustered isolates into 12 flagellar types. Flagellar type was distinct from neurotoxin type, and epidemiologically related isolates clustered together. Sequencing a larger PCR product, obtained during amplification of flaA1/A2 from type E strain Bennett identified a second flagellin gene, flaB. LC-MS analysis confirmed that flaB encoded a large type E-specific flagellin protein, and the predicted molecular mass for FlaB matched that observed by SDS-PAGE. In contrast, the molecular mass of FlaA was 2 to 12 kDa larger than the mass predicted by the flaA1/A2 sequence of a given strain, suggesting that FlaA is posttranslationally modified. While identification of FlaB, and the observation by SDS-PAGE of different masses of the FlaA proteins, showed the flagellin proteins of C. botulinum to be diverse, the presence of the flaA1/A2 gene in all strains examined facilitates single locus sequence typing of C. botulinum using the flagellin variable region. PMID- 17351098 TI - The dasABC gene cluster, adjacent to dasR, encodes a novel ABC transporter for the uptake of N,N'-diacetylchitobiose in Streptomyces coelicolor A3(2). AB - N,N'-Diacetylchitobiose [(GlcNAc)(2)] induces the transcription of chitinase (chi) genes in Streptomyces coelicolor A3(2). Physiological studies showed that (GlcNAc)(2) addition triggered chi expression and increased the rate of (GlcNAc)(2) concentration decline in culture supernatants of mycelia already cultivated with (GlcNAc)(2), suggesting that (GlcNAc)(2) induced the synthesis of its own uptake system. Four open reading frames (SCO0531, SCO0914, SCO2946, and SCO5232) encoding putative sugar-binding proteins of ABC transporters were found in the genome by probing the 12-bp repeat sequence required for regulation of chi transcription. SCO5232, named dasA, showed transcriptional induction by (GlcNAc)(2) and N,N',N'''-triacetylchitotriose [(GlcNAc)(3)]. Surface plasmon resonance analysis showed that recombinant DasA protein exhibited the highest affinity for (GlcNAc)(2) (equilibrium dissociation constant [K(D)] = 3.22 x 10( 8)). In the dasA-null mutant, the rate of decline of the (GlcNAc)(2) concentration in the culture supernatant was about 25% of that in strain M145. The in vitro and in vivo data clearly demonstrated that dasA is involved in (GlcNAc)(2) uptake. Upstream and downstream of dasA, the transcriptional regulator gene (dasR) and two putative integral membrane protein genes (dasBC) are located in the opposite and same orientations, respectively. The expression of dasR and dasB, which seemed independent of dasA transcription, was also induced by (GlcNAc)(2) and (GlcNAc)(3). PMID- 17351099 TI - Automated image analysis for quantitative fluorescence in situ hybridization with environmental samples. AB - When fluorescence in situ hybridization (FISH) analyses are performed with complex environmental samples, difficulties related to the presence of microbial cell aggregates and nonuniform background fluorescence are often encountered. The objective of this study was to develop a robust and automated quantitative FISH method for complex environmental samples, such as manure and soil. The method and duration of sample dispersion were optimized to reduce the interference of cell aggregates. An automated image analysis program that detects cells from 4',6' diamidino-2-phenylindole (DAPI) micrographs and extracts the maximum and mean fluorescence intensities for each cell from corresponding FISH images was developed with the software Visilog. Intensity thresholds were not consistent even for duplicate analyses, so alternative ways of classifying signals were investigated. In the resulting method, the intensity data were divided into clusters using fuzzy c-means clustering, and the resulting clusters were classified as target (positive) or nontarget (negative). A manual quality control confirmed this classification. With this method, 50.4, 72.1, and 64.9% of the cells in two swine manure samples and one soil sample, respectively, were positive as determined with a 16S rRNA-targeted bacterial probe (S-D-Bact-0338-a A-18). Manual counting resulted in corresponding values of 52.3, 70.6, and 61.5%, respectively. In two swine manure samples and one soil sample 21.6, 12.3, and 2.5% of the cells were positive with an archaeal probe (S-D-Arch-0915-a-A-20), respectively. Manual counting resulted in corresponding values of 22.4, 14.0, and 2.9%, respectively. This automated method should facilitate quantitative analysis of FISH images for a variety of complex environmental samples. PMID- 17351100 TI - VanA-type enterococci from humans, animals, and food: species distribution, population structure, Tn1546 typing and location, and virulence determinants. AB - VanA-type human (n=69), animal (n=49), and food (n=36) glycopeptide-resistant enterococci (GRE) from different geographic areas were investigated to study their possible reservoirs and transmission routes. Pulsed-field gel electrophoresis (PFGE) revealed two small genetically related clusters, M39 (n=4) and M49 (n=13), representing Enterococcus faecium isolates from animal and human feces and from clinical and fecal human samples. Multilocus sequence typing showed that both belonged to the epidemic lineage of CC17. purK allele analysis of 28 selected isolates revealed that type 1 was prevalent in human strains (8/11) and types 6 and 3 (14/15) were prevalent in poultry (animals and meat). One hundred and five of the 154 VanA GRE isolates, encompassing different species, origins, and PFGE types, were examined for Tn1546 type and location (plasmid or chromosome) and the incidence of virulence determinants. Hybridization of S1- and I-CeuI-digested total DNA revealed a plasmid location in 98% of the isolates. Human intestinal and animal E. faecium isolates bore large (>150 kb) vanA plasmids. Results of PCR-restriction fragment length polymorphism and sequencing showed the presence of prototype Tn1546 in 80% of strains and the G-to-T mutation at position 8234 in three human intestinal and two pork E. faecium isolates. There were no significant associations (P>0.5) between Tn1546 type and GRE source or enterococcal species. Virulence determinants were detected in all reservoirs but were significantly more frequent (P<0.02) among clinical strains. Multiple determinants were found in clinical and meat Enterococcus faecalis isolates. The presence of indistinguishable vanA elements (mostly plasmid borne) and virulence determinants in different species and PFGE-diverse populations in the presence of host-specific purK housekeeping genes suggested that all GRE might be potential reservoirs of resistance determinants and virulence traits transferable to human-adapted clusters. PMID- 17351101 TI - Effect of the mycorrhizosphere on the genotypic and metabolic diversity of the bacterial communities involved in mineral weathering in a forest soil. AB - To date, several bacterial species have been described as mineral-weathering agents which improve plant nutrition and growth. However, the possible relationships between mineral-weathering potential, taxonomic identity, and metabolic ability have not been investigated thus far. In this study, we characterized a collection of 61 bacterial strains isolated from Scleroderma citrinum mycorrhizae, the mycorrhizosphere, and the adjacent bulk soil in an oak forest. The ability of bacteria to weather biotite was assessed with a new microplate bioassay that measures the pH and the quantity of iron released from this mineral. We showed that weathering bacteria occurred more frequently in the vicinity of S. citrinum than in the bulk soil. Moreover, the weathering efficacy of the mycorrhizosphere bacterial isolates was significantly greater than that of the bulk soil isolates. All the bacterial isolates were identified by partial 16S rRNA gene sequence analysis as members of the genera Burkholderia, Collimonas, Pseudomonas, and Sphingomonas, and their carbon metabolism was characterized by the BIOLOG method. The most efficient isolates belonged to the genera Burkholderia and Collimonas. Multivariate analysis resulted in identification of three metabolic groups, one of which contained mainly bacterial isolates associated with S. citrinum and exhibiting high mineral-weathering potential. Therefore, our results support the hypothesis that by its carbon metabolism this fungus selects in the bulk soil reservoir a bacterial community with high weathering potential, and they also address the question of functional complementation between mycorrhizal fungi and bacteria in the ectomycorrhizal complex for the promotion of tree nutrition. PMID- 17351102 TI - A novel reductive dehalogenase, identified in a contaminated groundwater enrichment culture and in Desulfitobacterium dichloroeliminans strain DCA1, is linked to dehalogenation of 1,2-dichloroethane. AB - A mixed culture dechlorinating 1,2-dichloroethane (1,2-DCA) to ethene was enriched from groundwater that had been subjected to long-term contamination. In the metagenome of the enrichment, a 7-kb reductive dehalogenase (RD) gene cluster sequence was detected by inverse and direct PCR. The RD gene cluster had four open reading frames (ORF) showing 99% nucleotide identity with pceB, pceC, pceT, and orf1 of Dehalobacter restrictus strain DSMZ 9455(T), a bacterium able to dechlorinate chlorinated ethenes. However, dcaA, the ORF encoding the catalytic subunit, showed only 94% nucleotide and 90% amino acid identity with pceA of strain DSMZ 9455(T). Fifty-three percent of the amino acid differences were localized in two defined regions of the predicted protein. Exposure of the culture to 1,2-DCA and lactate increased the dcaA gene copy number by 2 log units, and under these conditions the dcaA and dcaB genes were actively transcribed. A very similar RD gene cluster with 98% identity in the dcaA gene sequence was identified in Desulfitobacterium dichloroeliminans strain DCA1, the only known isolate that selectively dechlorinates 1,2-DCA but not chlorinated ethenes. The dcaA gene of strain DCA1 possesses the same amino acid motifs as the new dcaA gene. Southern hybridization using total genomic DNA of strain DCA1 with dcaA gene-specific and dcaB- and pceB-targeting probes indicated the presence of two identical or highly similar dehalogenase gene clusters. In conclusion, these data suggest that the newly described RDs are specifically adapted to 1,2-DCA dechlorination. PMID- 17351103 TI - Modulation of heroin and cocaine self-administration by dopamine D1- and D2-like receptor agonists in rhesus monkeys. AB - Cocaine-heroin combinations ("speedballs") are commonly self-administered by polydrug abusers. Speedball self-administration may reflect in part an enhancement of the reinforcing effects of the drug combination compared with either drug alone. The present study investigated the degree to which the dopamine receptor system plays a role in cocaine-induced enhancement of heroin self-administration. In rhesus monkeys trained under a progressive ratio schedule of i.v. drug injection, combining heroin with cocaine shifted the heroin dose response function leftward, and isobolographic analysis indicated that the combined effects were dose-additive. Likewise, combining heroin with the D1-like receptor agonists 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-(1H)-3 benzazepine HCl (SKF 81297) and 6-chloro-N-allyl-7,8-dihydroxy-1-phenyl-2,3,4,5 tetrahydro-[1H]-3-benzazepine (SKF 82958) resulted in a leftward shift in the heroin dose-response function that was dose-additive. In contrast, combining heroin with the D2-like agonists R-(-)-propylnorapomorphine (NPA) and quinpirole shifted the heroin dose-response function to the right. Isobolographic analysis of the combined effects of heroin with NPA and quinpirole revealed infra-additive interactions in both cases. When combined with cocaine instead of heroin, both the D1-like receptor agonist SKF 81297 and the D2-like receptor agonist NPA enhanced cocaine self-administration. The combinations of SKF 81297 with cocaine were dose additive; however, the NPA-cocaine interaction was infra-additive. Together, the results suggest that D1- and D2-like receptor mechanisms may play qualitatively different roles in the combined self-administration of heroin and cocaine. In particular, stimulation of D1-like receptors enhances self administration of heroin or cocaine individually, similar to the effects of combining cocaine with heroin, whereas stimulation of D2-like receptors seems to play primarily an inhibitory role. PMID- 17351104 TI - In vitro and in vivo pharmacological characterization of ethyl-4-[trans-4-[((2S) 2-hydroxy-3-[4-hydroxy-3[(methylsulfonyl)amino]-phenoxy]propyl) amino]cyclohexyl]benzoate hydrochloride (SAR150640), a new potent and selective human beta3-adrenoceptor agonist for the treatment of preterm labor. AB - Ethyl-4-[trans-4-[((2S)-2-hydroxy-3-[4-hydroxy-3[(methylsulfonyl)amino] phenoxy]propyl) amino]cyclohexyl]benzoate hydrochloride (SAR150640) was characterized as a new potent and selective beta(3)-adrenoceptor agonist for the treatment of preterm labor. SAR150640 and its major metabolite, the corresponding acid 4-[trans-4-[((2S)-2-hydroxy-3-[4-hydroxy-3[(methylsulfonyl) amino] phenoxy]propyl)amino]cyclohexyl]benzoic acid (SSR500400), showed high affinity for beta(3)-adrenoceptors (K(i) = 73 and 358 nM) and greater potency than (-) isoproterenol in increasing cAMP production in membrane preparations from human neuroblastoma cells (SKNMC), which express native beta(3)-adrenoceptors (pEC(50) = 6.5, 6.2, and 5.1, respectively). SAR150640 and SSR500400 also increased cAMP production in membrane preparations from human uterine smooth muscle cells (UtSMC), which also express native beta(3)-adrenoceptors (pEC(50) = 7.7 and 7.7, respectively). In these cells, SAR150640 dose-dependently inhibited oxytocin induced intracellular Ca(2+) mobilization and extracellular signal-regulated kinase 1/2 phosphorylation. SAR150640 and SSR500400 had no beta(1)- or beta(2) agonist or antagonist activity in guinea pig atrium and trachea, or in human isolated atrium and bronchus preparations. Both compounds concentration dependently inhibited spontaneous contractions in human near-term myometrial strips, with greater potency than salbutamol and 4-[3-[(1,1-dimethylethyl)-amino] 2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP12177) (pIC(50) = 6.4, 6.8, 5.9, and 5.8, respectively), but with similar potency to (-) isoproterenol and atosiban (oxytocin/vasopressin V(1)a receptor antagonist). SAR150640 also inhibited the contractions induced by oxytocin and prostaglandin F(2alpha). In vivo, after intravenous administration, SAR150640 (1 and 6 mg/kg), but not atosiban (6 mg/kg), dose-dependently inhibited myometrial contractions in conscious unrestrained female cynomolgus monkeys, with no significant effects on heart rate or blood pressure. In contrast, salbutamol (50 and 250 microg/kg) had no inhibitory effect on uterine contractions, but it dose-dependently increased heart rate. These findings indicate a potential for the therapeutic use of SAR150640 in mammals during preterm labor. PMID- 17351105 TI - Chlorambucil cytotoxicity in malignant B lymphocytes is synergistically increased by 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026)-mediated inhibition of DNA double-strand break repair via inhibition of DNA-dependent protein kinase. AB - Chlorambucil (CLB) treatment is used in chronic lymphocytic leukemia (CLL) but resistance to CLB develops in association with accelerated repair of CLB-induced DNA damage. Phosphorylated histone H2AX (gammaH2AX) is located at DNA double strand break (DSB) sites; furthermore, it recruits and retains damage-responsive proteins. This damage can be repaired by nonhomologous DNA end-joining (NHEJ) and/or homologous recombinational repair (HR) pathways. A key component of NHEJ is the DNA-dependent protein kinase (DNA-PK) complex. Increased DNA-PK activity is associated with resistance to CLB in CLL. We used the specific DNA-PK inhibitor 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026) to sensitize CLL cells to chlorambucil. Our results indicate that in a CLL cell line (I83) and in primary CLL-lymphocytes, chlorambucil plus NU7026 has synergistic cytotoxic activity at nontoxic doses of NU7026. CLB treatment results in G(2)/M phase arrest, and NU7026 increases this CLB-induced G(2)/M arrest. Moreover, a kinetic time course demonstrates that CLB-induced DNA-PK activity was inhibited by NU7026, providing direct evidence of the ability of NU7026 to inhibit DNA-PK function. DSBs, visualized as gammaH2AX, were enhanced 24 to 48 h after CLB and further increased by CLB plus NU7026, suggesting that the synergy of the combination is mediated by NU7026 inhibition of DNA-PK with subsequent inhibition of DSB repair. PMID- 17351106 TI - Ethonafide-induced cytotoxicity is mediated by topoisomerase II inhibition in prostate cancer cells. AB - Ethonafide is an anthracene-containing derivative of amonafide that belongs to the azonafide series of anticancer agents. The lack of cross-resistance in multidrug-resistant cancer cell lines and the absence of a quinone and hydroquinone moiety make ethonafide a potentially less cardiotoxic replacement for existing anthracene-containing anticancer agents. For this study, we investigated the anticancer activity and mechanism of ethonafide in human prostate cancer cell lines. Ethonafide was cytotoxic against three human prostate cancer cell lines at nanomolar concentrations. Ethonafide was found to be better tolerated and more effective at inhibiting tumor growth compared with mitoxantrone in a human xenograft tumor regression mouse model. Mechanistically, we found that ethonafide inhibited topoisomerase II activity by stabilizing the enzyme-DNA complex, involving both topoisomerase IIalpha and -beta. In addition, ethonafide induced a potent G(2) cell cycle arrest in the DU 145 human prostate cancer cell line. By creating stable cell lines with decreased expression of topoisomerase IIalpha or -beta, we found that a decrease in topoisomerase IIalpha protein expression renders the cell line resistant to ethonafide. The decrease in sensitivity to ethonafide was associated with a decrease in DNA damage and an increase in DNA repair as measured by the neutral comet assay. These data demonstrate that ethonafide is a topoisomerase II poison and that it is topoisomerase IIalpha-specific in the DU 145 human prostate cancer cell line. PMID- 17351107 TI - Nicotinic facilitation of delta9-tetrahydrocannabinol discrimination involves endogenous anandamide. AB - Systemic administration of the main active ingredient in cannabis, Delta9 tetrahydrocannabinol (THC), alters extracellular levels of acetylcholine in several brain areas, suggesting an involvement of the cholinergic system in the psychotropic effects of cannabis. Here, we investigated whether drugs acting at either nicotinic or muscarinic receptors can modulate the discriminative effects of THC. In rats that had learned to discriminate effects of 3 mg/kg i.p. injections of THC from injections of vehicle, the nicotinic agonist nicotine (0.1 0.56 mg/kg subcutaneous) and the muscarinic agonist pilocarpine (0.3-3 mg/kg i.p.) did not produce THC-like effects, but they both potentiated the discriminative effects of low doses of THC (0.3-1 mg/kg). Neither the nicotinic antagonist mecamylamine (1-5.6 mg/kg i.p.) nor the muscarinic antagonist scopolamine (0.01-0.1 mg/kg i.p.) altered the discriminative effects of THC, but they blocked the potentiation of discriminative effects of THC by nicotine and pilocarpine, respectively. The cannabinoid CB(1) antagonist rimonabant (1 mg/kg i.p.) reversed nicotine- but not pilocarpine-induced potentiation of THC discrimination, suggesting that nicotine potentiation is, at least in part, mediated by release of endogenous cannabinoids in the brain. In addition, when metabolic degradation of the endogenous cannabinoid anandamide was blocked by the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3' carbamoylbiphenil-3-yl-ester (URB-597; 0.3 mg/kg i.p.) nicotine, but not pilocarpine, produced significant THC-like discriminative effects that were antagonized by rimonabant. Our results suggest that nicotinic and muscarinic cholinergic receptors modulate the discriminative effects of THC by fundamentally different mechanisms. Nicotinic, but not muscarinic, modulation of THC discrimination involves elevations in endogenous levels of anandamide. PMID- 17351108 TI - Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. AB - New Zealand black (NZB) mice with autoimmune and B lymphoproliferative disease (B LPD) are a model for human chronic lymphocytic leukemia (CLL). A genomewide linkage scan of the NZB loci associated with lymphoma was conducted in F1 backcrosses of NZB and a control strain, DBA/2. Of 202 mice phenotyped for the presence or absence of LPD, surface maker expression, DNA content, and microsatellite polymorphisms, 74 had disease. The CD5(+), IgM(+), B220(dim), hyperdiploid LPD was linked to 3 loci on chromosomes 14, 18, and 19 that are distinct from previously identified autoimmunity-associated loci. The region of synteny with mouse D14mit160 is the human 13q14 region, associated with human CLL, containing microRNAs mir-15a16-1. DNA sequencing of multiple NZB tissues identified a point mutation in the 3' flanking sequence of the identical microRNA, mir-16-1, and this mutation was not present in other strains, including the nearest neighbor, NZW. Levels of miR-16 were decreased in NZB lymphoid tissue. Exogenous miR-16 delivered to an NZB malignant B-1 cell line resulted in cell-cycle alterations and increased apoptosis. Linkage of the mir-15a/16-1 complex and the development of B-LPD in this spontaneous mouse model suggest that the altered expression of the mir-15a/16-1 is the molecular lesion in CLL. PMID- 17351109 TI - Human tissue mast cells are an inducible reservoir of persistent HIV infection. AB - We have proposed that, unlike other HIV-vulnerable cell lineages, progenitor mast cells (prMCs), cultured in vitro from undifferentiated bone marrow-derived CD34(+) pluripotent progenitors (PPPs), are susceptible to infection during a limited period of their ontogeny. As infected prMCs mature in culture, they lose expression of viral chemokine coreceptors necessary for viral entry and develop into long-lived, latently infected mature tissue mast cells (MCs), resistant to new infection. In vivo recruitment of prMCs to different tissue compartments occurs in response to tissue injury, growth, and remodeling or allergic inflammation, allowing populations of circulating and potentially HIV-susceptible prMCs to spread persistent infection to diverse tissue compartments. In this report, we provide in vivo evidence to confirm this model by demonstrating that HIV-infected women have both circulating prMCs and placental tissue MCs (PLMCs) that harbor inducible infectious HIV even after highly active antiretroviral therapy (HAART) during pregnancy. Furthermore, infectious virus, capable of infecting alloactivated fetal cord blood mononuclear cells (CBMCs), could be induced in isolated latently infected PLMCs after weeks in culture in vitro. These data provide the first in vivo evidence that tissue MCs, developed from infected circulating prMCs, comprise a long-lived inducible reservoir of persistent HIV in infected persons during HAART. PMID- 17351110 TI - A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia. AB - This phase 2 study evaluated the efficacy and safety of the oral farnesyltransferase inhibitor tipifarnib in adults with refractory or relapsed acute myeloid leukemia (AML). Patients (n=252) received tipifarnib 600 mg twice a day for 21 days in 28-day cycles. Median age was 62 years; 99 (39%) patients were 65 years or older. Eleven (4%) of 252 patients achieved complete remission (CR) or complete remission with incomplete platelet recovery (CRp; 9 CR and 2 CRp). Nineteen patients (8%), including those who achieved CR/CRp, achieved a reduction in bone marrow blasts to less than 5% blasts. Bone marrow blasts were reduced more than 50% in an additional 8 patients (total = 27; 11%). Median survival was 369 days for patients who achieved CR/CRp. Myelosuppression was the most common adverse event. The most common nonhematologic toxicities were fever, nausea, and hypokalemia. Single-agent treatment with tipifarnib induced durable CR/CRp, which was associated with prolonged survival, in some patients with refractory or relapsed AML. The response rate observed in this heavily pretreated group of patients suggests the requirement to enhance the response rate either by combining tipifarnib with other active agents or determining factors that are predictive of response. PMID- 17351111 TI - A novel proteoliposomal vaccine elicits potent antitumor immunity in mice. AB - Therapeutic vaccination against idiotype is a promising strategy for immunotherapy of B-cell malignancies. Its feasibility, however, is limited by the requirement for a patient-specific product. Here we describe a novel vaccine formulation prepared by simply extracting cell-membrane proteins from lymphoma cells and incorporating them together with IL-2 into proteoliposomes. The vaccine was produced in 24 hours, compared with more labor-intensive and time-consuming hybridoma or recombinant DNA methods. The vaccine elicited T-cell immunity in vivo, as demonstrated by secretion of type 1 cytokines. It protected against tumor challenge at doses of tumor antigen 50 to 100 times lower than that previously observed using either liposomes formulated with IL-2 and secreted lymphoma immunoglobulin or a prototype vaccine consisting of lymphoma immunoglobulin conjugated to keyhole limpet hemocyanin. The increased potency justifies testing similar patient-specific human vaccines prepared using extracts from primary tumor samples. PMID- 17351112 TI - EGO, a novel, noncoding RNA gene, regulates eosinophil granule protein transcript expression. AB - Gene expression profiling of early eosinophil development shows increased transcript levels of proinflammatory cytokines, chemokines, transcription factors, and a novel gene, EGO (eosinophil granule ontogeny). EGO is nested within an intron of the inositol triphosphate receptor type 1 (ITPR1) gene and is conserved at the nucleotide level; however, the largest open reading frame (ORF) is 86 amino acids. Sucrose density gradients show that EGO is not associated with ribosomes and therefore is a noncoding RNA (ncRNA). EGO transcript levels rapidly increase following interleukin-5 (IL-5) stimulation of CD34(+) hematopoietic progenitors. EGO RNA also is highly expressed in human bone marrow and in mature eosinophils. RNA silencing of EGO results in decreased major basic protein (MBP) and eosinophil derived neurotoxin (EDN) mRNA expression in developing CD34(+) hematopoietic progenitors in vitro and in a CD34(+) cell line model. Therefore, EGO is a novel ncRNA gene expressed during eosinophil development and is necessary for normal MBP and EDN transcript expression. PMID- 17351113 TI - ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia. AB - Extracellular signal-regulated kinase-1/2 (ERK1/2) is frequently found constitutively activated (p-ERK1/2) in hematopoietic diseases, suggesting a role in leukemogenesis. The aim of this study was to assess the expression and clinical role of p-ERK1/2 in adult acute lymphoblastic leukemia (ALL). In 131 primary samples from adult de novo ALL patients enrolled in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acute Linfoide (LAL) 2000 protocol and evaluated by flow cytometry, constitutive ERK1/2 activation was found in 34.5% of cases; these results were significantly associated with higher white blood cell (WBC) values (P=.013). In a multivariate analysis, p-ERK1/2 expression was an independent predictor of complete remission achievement (P=.027). Effective approaches toward MEK inhibition need to be explored in order to evaluate whether this may represent a new therapeutic strategy for adult ALL patients. PMID- 17351114 TI - A core subunit of the RNA-processing/degrading exosome specifically influences cuticular wax biosynthesis in Arabidopsis. AB - The cuticle is an extracellular matrix composed of cutin polyester and waxes that covers aerial organs of land plants and protects them from environmental stresses. The Arabidopsis thaliana cer7 mutant exhibits reduced cuticular wax accumulation and contains considerably lower transcript levels of ECERIFERUM3/WAX2/YORE-YORE (CER3/WAX2/YRE), a key wax biosynthetic gene. We show here that CER7 protein is a putative 3'-5' exoribonuclease homologous to yeast Ribonuclease PH45 (RRP45p), a core subunit of the RNA processing and degrading exosome that controls the expression of CER3/WAX2/YRE. We propose that CER7 acts by degrading a specific mRNA species encoding a negative regulator of CER3/WAX2/YRE transcription. A second RRP45p homolog found in Arabidopsis, designated At RRP45a, is partially functionally redundant with CER7, and complete loss of RRP45 function in Arabidopsis is lethal. To our knowledge, CER7 is currently the only example of a core exosomal subunit specifically influencing a cellular process. PMID- 17351115 TI - The Arabidopsis aba4-1 mutant reveals a specific function for neoxanthin in protection against photooxidative stress. AB - The aba4-1 mutant completely lacks neoxanthin but retains all other xanthophyll species. The missing neoxanthin in light-harvesting complex (Lhc) proteins is compensated for by higher levels of violaxanthin, albeit with lower capacity for photoprotection compared with proteins with wild-type levels of neoxanthin. Detached leaves of aba4-1 were more sensitive to oxidative stress than the wild type when exposed to high light and incubated in a solution of photosensitizer agents. Both treatments caused more rapid pigment bleaching and lipid oxidation in aba4-1 than wild-type plants, suggesting that neoxanthin acts as an antioxidant within the photosystem II (PSII) supercomplex in thylakoids. While neoxanthin-depleted Lhc proteins and leaves had similar sensitivity as the wild type to hydrogen peroxide and singlet oxygen, they were more sensitive to superoxide anions. aba4-1 intact plants were not more sensitive than the wild type to high-light stress, indicating the existence of compensatory mechanisms of photoprotection involving the accumulation of zeaxanthin. However, the aba4-1 npq1 double mutant, lacking zeaxanthin and neoxanthin, underwent stronger PSII photoinhibition and more extensive oxidation of pigments than the npq1 mutant, which still contains neoxanthin. We conclude that neoxanthin preserves PSII from photoinactivation and protects membrane lipids from photooxidation by reactive oxygen species. Neoxanthin appears particularly active against superoxide anions produced by the Mehler's reaction, whose rate is known to be enhanced in abiotic stress conditions. PMID- 17351116 TI - Impairment of cellulose synthases required for Arabidopsis secondary cell wall formation enhances disease resistance. AB - Cellulose is synthesized by cellulose synthases (CESAs) contained in plasma membrane-localized complexes. In Arabidopsis thaliana, three types of CESA subunits (CESA4/IRREGULAR XYLEM5 [IRX5], CESA7/IRX3, and CESA8/IRX1) are required for secondary cell wall formation. We report that mutations in these proteins conferred enhanced resistance to the soil-borne bacterium Ralstonia solanacearum and the necrotrophic fungus Plectosphaerella cucumerina. By contrast, susceptibility to these pathogens was not altered in cell wall mutants of primary wall CESA subunits (CESA1, CESA3/ISOXABEN RESISTANT1 [IXR1], and CESA6/IXR2) or POWDERY MILDEW-RESISTANT5 (PMR5) and PMR6 genes. Double mutants indicated that irx-mediated resistance was independent of salicylic acid, ethylene, and jasmonate signaling. Comparative transcriptomic analyses identified a set of common irx upregulated genes, including a number of abscisic acid (ABA) responsive, defense-related genes encoding antibiotic peptides and enzymes involved in the synthesis and activation of antimicrobial secondary metabolites. These data as well as the increased susceptibility of ABA mutants (abi1-1, abi2 1, and aba1-6) to R. solanacearum support a direct role of ABA in resistance to this pathogen. Our results also indicate that alteration of secondary cell wall integrity by inhibiting cellulose synthesis leads to specific activation of novel defense pathways that contribute to the generation of an antimicrobial-enriched environment hostile to pathogens. PMID- 17351117 TI - The thylakoid lumen protease Deg1 is involved in the repair of photosystem II from photoinhibition in Arabidopsis. AB - Deg1 is a Ser protease peripherally attached to the lumenal side of the thylakoid membrane. Its physiological function is unknown, but its localization makes it a suitable candidate for participation in photoinhibition repair by degradation of the photosystem II reaction center protein D1. We transformed Arabidopsis thaliana with an RNA interference construct and obtained plants with reduced levels of Deg1. These plants were smaller than wild-type plants, flowered earlier, were more sensitive to photoinhibition, and accumulated more of the D1 protein, probably in an inactive form. Two C-terminal degradation products of the D1 protein, of 16 and 5.2 kD, accumulated at lower levels compared with the wild type. Moreover, addition of recombinant Deg1 to inside-out thylakoid membranes isolated from the mutant could induce the formation of the 5.2-kD D1 C-terminal fragment, whereas the unrelated proteases trypsin and thermolysin could not. Immunoblot analysis revealed that mutants containing less Deg1 also contain less FtsH protease, and FtsH mutants contain less Deg1. These results suggest that Deg1 cooperates with the stroma-exposed proteases FtsH and Deg2 in degrading D1 protein during repair from photoinhibition by cleaving lumen-exposed regions of the protein. In addition, they suggest that accumulation of Deg1 and FtsH proteases may be coordinated. PMID- 17351119 TI - Management of Morel-Lavallee lesion of the knee: twenty-seven cases in the national football league. AB - BACKGROUND: The Morel-Lavallee lesion is a closed degloving injury most commonly described in the region of the hip joint after blunt trauma. It also occurs in the knee as a result of shearing trauma during football and is a distinct lesion from prepatellar bursitis and quadriceps contusion. PURPOSE: To review the authors' experience with Morel-Lavallee lesion of the knee in the elite contact athlete to construct a diagnostic and treatment algorithm. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-seven knees in 24 players were identified from 1 National Football League team's annual injury database as having sustained a Morel-Lavallee lesion between 1993 and 2006. Their charts were retrospectively reviewed. RESULTS: The most common mechanism of injury was a shearing blow on the playing surface (81%). The most common motion deficit was active flexion (41%). The mean time for resolution of the fluid collection and achievement of full active flexion was 16.3 days. The mean number of practices missed was 1.5. The mean number of games missed was 0.1. Fourteen knees (52%) were treated successfully with compression wrap, cryotherapy, and motion exercises. Thirteen knees (48%) were treated with at least 1 aspiration, and 6 knees (22%) were treated with multiple aspirations for recurrent serosanguineous fluid collections. In 3 cases (11%), the Morel-Lavallee lesion was successfully treated with doxycycline sclerodesis after 3 aspirations failed to resolve the recurrent fluid collections; return to play was immediate thereafter in each case. CONCLUSION: In football, Morel-Lavallee lesion of the knee usually occurs from a shearing blow from the playing field. Diagnosis is confirmed when examination reveals a large suprapatellar area of palpable fluctuance. Elite athletes are typically able to return to practice and game play long before complete resolution of the lesion. Recurrent fluid collections can occur, necessitating aspiration in approximately half the cases for successful treatment. Recalcitrant fluid collections can be safely and expeditiously treated with doxycycline sclerodesis. PMID- 17351120 TI - Arthroscopic treatment of the painful "internal" snapping hip: results of a new endoscopic technique and imaging protocol. AB - BACKGROUND: Traditional surgical treatment for a painful snapping iliopsoas tendon has been an open lengthening of the tendon. HYPOTHESIS: An endoscopic release will alleviate painful snapping of the tendon. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Six patients with painful snapping hips who had no pain relief after magnetic resonance arthrography, which included injection of bupivacaine into the hip joint, subsequently had an ultrasound evaluation of their iliopsoas tendons and an anesthetic injection into the psoas bursa. In all 6 patients, the injection relieved their hip pain, and in 4, real-time imaging demonstrated snapping of the tendon. All hips were evaluated with the 100-point Harris hip scoring system before and at 1.5, 3, 6, and 12 months after surgery. RESULTS: Preoperative hip scores averaged 58 points. After surgery, all patients had hip flexor weakness, used crutches for 5 weeks, and had 6-week scores that averaged 62 points. The patients continued to improve, and at 6 and 12 months, their scores averaged 90 and 96 points, respectively, and none had recurrence of their snapping or pain. CONCLUSION: Ultrasound-guided anesthetic injection of the psoas bursa is useful to confirm snapping of the iliopsoas tendon as the cause of a patient's hip pain. Endoscopic release of the tendon is a safe outpatient procedure that provides effective relief of the snapping and pain. PMID- 17351118 TI - Integration of chloroplast nucleic acid metabolism into the phosphate deprivation response in Chlamydomonas reinhardtii. AB - Cell survival depends on the cell's ability to acclimate to phosphorus (P) limitation. We studied the chloroplast ribonuclease polynucleotide phosphorylase (PNPase), which consumes and generates phosphate, by comparing wild-type Chlamydomonas reinhardtii cells with strains with reduced PNPase expression. In the wild type, chloroplast RNA (cpRNA) accumulates under P limitation, correlating with reduced PNPase expression. PNPase-deficient strains do not exhibit cpRNA variation under these conditions, suggesting that in the wild type PNPase limits cpRNA accumulation under P stress. PNPase levels appear to be mediated by the P response regulator PHOSPHORUS STARVATION RESPONSE1 (PSR1), because in psr1 mutant cells, cpRNA declines under P limitation and PNPase expression is not reduced. PNPase-deficient cells begin to lose viability after 24 h of P depletion, suggesting that PNPase is important for cellular acclimation. PNPase-deficient strains do not have enhanced sensitivity to other physiological or nutrient stresses, and their RNA and cell growth phenotypes are not observed under P stress with phosphite, a phosphate analog that blocks the stress signal. In contrast with RNA metabolism, chloroplast DNA (cpDNA) levels declined under P deprivation, suggesting that P mobilization occurs from DNA rather than RNA. This unusual phenomenon, which is phosphite- and PSR1 insensitive, may have evolved as a result of the polyploid nature of cpDNA and the requirement of P for cpRNA degradation by PNPase. PMID- 17351121 TI - Activity level and subjective knee function 15 years after anterior cruciate ligament injury: a prospective, longitudinal study of nonreconstructed patients. AB - BACKGROUND: The activity level and subjective knee function after an anterior cruciate ligament (ACL) injury treated without reconstruction have not been well elucidated. HYPOTHESIS: Patients with ACL injury can achieve good knee function and satisfactory long-term activity level when treated by early activity modification combined with rehabilitation. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. MATERIALS AND METHODS: One hundred patients with an acute total ACL injury were observed for 15 years. All patients initially underwent arthroscopic surgery and a rehabilitation program. They were advised to modify their activity level, especially by avoiding contact sports. Patients with recurrent giving-way episodes and/or secondary meniscal injuries that required fixation (n = 6) were subsequently excluded and underwent reconstruction (n = 22). Sixty-seven patients with unilateral nonreconstructed ACL injury remained at the 15-year follow-up. The Lysholm knee score, Tegner activity level, and a visual analog score for global knee function were recorded at regular intervals. At the final follow-up, patients were further evaluated with the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective knee evaluation form. RESULTS: Forty patients resumed their preinjury activity level or higher within 3 years. The median activity level 15 years after injury had decreased from 7 to 4 according to Tegner activity scale (P < .001). The mean Lysholm knee score was 96 and 95, 1 and 3 years after injury, respectively, but declined to 86 after 15 years (P < .001). Forty-nine patients had good/excellent results, and 14 had fair (n = 6) or poor function (n = 8) at 15 years. Patients injured in contact sports scored lower in the quality of life sub-scale of KOOS than those injured in noncontact sports (P < .05). Thirteen of the 67 patients (19%) were reoperated with an arthroscopic procedure because of knee symptoms. CONCLUSION: Early activity modification and neuromuscular rehabilitation resulted in a good knee function and an acceptable activity level in the majority of the nonreconstructed patients. The decline in activity level of patients engaged in contact sports at the time of injury affected their subjective quality of life more than patients involved in noncontact sports. PMID- 17351122 TI - Clinical, histologic, and radiographic outcomes of distal femoral resurfacing with hypothermically stored osteoarticular allografts. AB - BACKGROUND: Fresh osteoarticular allograft transplantation has a long history of clinical success. These grafts have typically been implanted less than 1 week from donor asystole. HYPOTHESIS: Osteoarticular allografts stored 4 to 6 weeks represent a viable alternative to treat full-thickness cartilage and osteochondral defects of the distal femur as measured by clinical, histologic, and magnetic resonance imaging (MRI) criteria. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Osteoarticular allografts were implanted after a mean graft storage time (at 4 degrees C) of 36 days (range, 28-43). Sixty-seven patients received massive hypothermically stored osteoarticular allografts. Ten knees in 8 of these patients underwent second-look arthroscopic evaluation and biopsy at a mean of 40 months (range, 23-60) after implantation. Clinical assessment was performed using multiple outcome measures and sequential MRI evaluations. Biopsy specimens were obtained from the graft as well as from native articular cartilage at the time of second-look arthroscopy for histologic analysis. RESULTS: The mean International Knee Documentation Committee scores were as follows: preoperative, 27 (range, 9-55); postoperative, 79 (range, 56 99); P = .002. The mean Lysholm scores were as follows: preoperative, 37 (range, 12-47); postoperative, 78 (range, 55-90); P = .002. The mean Short Form-36 physical scores were as follows: preoperative, 38 (range, 24-55); postoperative, 51 (range, 39-61); P = .002. The mean Tegner scores were as follows: preoperative, 4.3 (range, 1-9); postoperative, 5.3 (range, 4-7); P = .16. The mean International Cartilage Repair Society score at follow-up was 10 (nearly normal) (range, 7-11). The mean modified Outerbridge scores were as follows: preoperative, 4.3 (range, 3-5); postoperative, 0.6 (range, 0-1); P = .002. The mean graft and native cartilage cellular density and viability were not statistically different. CONCLUSIONS: Fresh-stored osteoarticular grafts for full thickness articular surface defects of the distal femur appear to offer a viable biological method to restore knee function. Our study suggests that osteoarticular grafts stored in cell culture medium at 4 degrees C for 4 to 6 weeks provide successful short-term clinical outcomes. PMID- 17351123 TI - In vivo measurement of the pivot-shift test in the anterior cruciate ligament deficient knee using an electromagnetic device. AB - BACKGROUND: The pivot-shift test is commonly used for assessing dynamic instability in anterior cruciate ligament-insufficient knees, which is related to subjective knee function, unlike static load-displacement measurement. Conventional measurements of 3-dimensional position displacement cannot assess such dynamic instability in vivo and produce comparable parameters. Not only 3 dimensional position displacement but also its 3-dimensional acceleration should be measured for quantitative evaluation of the pivot-shift test. HYPOTHESIS: Knees with a positive pivot-shift test result have increased tibial anterior translation and acceleration of its subsequent posterior translation, and they are correlated with clinical grading. STUDY DESIGN: Controlled laboratory study. MATERIALS AND METHODS: Thirty patients with isolated anterior cruciate ligament injury were included. Pivot-shift tests were evaluated under anesthesia manually and experimentally using an electromagnetic knee 6 degrees of freedom measurement system. From 60 Hz of 6 degrees of freedom data, coupled tibial anterior translation was calculated, and acceleration of posterior translation was computed by secondary derivative. RESULTS: All anterior cruciate ligament deficient knees demonstrated a positive pivot-shift test result. The coupled tibial anterior translation was 7.7 and 15.6 mm in anterior cruciate ligament intact and -deficient knees, respectively. The acceleration of posterior translation was -797 and -2001 mm/s(2), respectively. These differences were significant (P < .01). The coupled tibial anterior translation and acceleration of posterior translation in the anterior cruciate ligament-deficient knee were larger in correlation with clinical grading (P = .03 and P < .01, respectively). CONCLUSION: The increase of tibial anterior translation and acceleration of subsequent posterior translation could be detected in knees with a positive pivot shift result, and this increase was correlated to clinical grading. CLINICAL RELEVANCE: These measurements can be used for quantified evaluation of dynamic instability demonstrated by the pivot-shift test. PMID- 17351124 TI - Catastrophic head injuries in high school and college football players. AB - BACKGROUND: Catastrophic head injuries in football are rare but tragic events. PURPOSE: To update the profile of catastrophic head injuries in high school and college football players and to describe relevant risk factors. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We reviewed 94 incidents of severe football head injuries reported to the National Center for Catastrophic Sports Injury Research during 13 academic years (September 1989 through June 2002). RESULTS: In the study period there were an average of 7.23 (standard deviation = 2.05) direct high school and college catastrophic head injuries in scholastic football participants per year. There were 0.67 injuries per 100 000 (95% confidence interval: 0.54, 0.81 per 100 000) high school and 0.21 injuries per 100 000 (95% confidence interval: 0.0, 0.49 per 100 000) college participants for a risk ratio of 3.28 (95% confidence interval: 0.81, 13.3). The injuries resulted in subdural hematoma in 75 athletes, subdural hematoma with diffuse brain edema in 10 athletes, diffuse brain edema in 5 athletes, and arteriovenous malformation or aneurysm in 4 athletes. Fifty-nine percent of the contacts reported that the athlete had a history of a previous head injury, of which 71% occurred within the same season as the catastrophic event. Thirty-nine percent of the athletes (21 of 54) were playing with residual neurologic symptoms from the prior head injury. There were 8 (9%) deaths as a result of the injury, 46 (51%) permanent neurologic injuries, and 36 (40%) serious injuries with full recovery. Most players sustained a major impact to the head either from tackling or being tackled. CONCLUSION: The incidence of catastrophic head injuries in football has remained low since the advent of the modern day football helmet in the early 1970s. The incidence of catastrophic head injuries in football is dramatically higher at the high school level than at the college level. Although the reason for this discrepancy is unclear, an unacceptably high percentage of high school players were playing with residual symptoms from a prior head injury. Coaches, athletes, athletic trainers, and medical personnel need to adhere to the guideline that an athlete with any neurologic symptoms from a head injury should be strongly discouraged from returning to play. PMID- 17351126 TI - Can medical schools teach high school students to be scientists? AB - The preeminence of science in the United States is endangered for multiple reasons, including mediocre achievement in science education by secondary school students. A group of scientists at Oregon Health and Science University has established a class to teach the process of scientific inquiry to local high school students. Prominent aspects of the class include pairing of the student with a mentor; use of a journal club format; preparation of a referenced, hypothesis driven research proposal; and a "hands-on" laboratory experience. A survey of our graduates found that 73% were planning careers in health or science. In comparison to conventional science classes, including chemistry, biology, and algebra, our students were 7 times more likely to rank the scientific inquiry class as influencing career or life choices. Medical schools should make research opportunities widely available to teenagers because this experience dramatically affects one's attitude toward science and the likelihood that a student will pursue a career in science or medicine. A federal initiative could facilitate student opportunities to pursue research. PMID- 17351125 TI - D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury. AB - Traumatic brain injury triggers a massive glutamate efflux, activation of NMDA receptor channels, and cell death. Recently, we reported that NMDA receptors in mice are down-regulated from hours to days following closed head injury (CHI), and treatment with NMDA improved recovery of motor and cognitive functions up to 14 d post-injury. Here we show that a single injection of a low dose of D cycloserine (DCS), a partial NMDA receptor agonist, in CHI mice 24 h post-injury, resulted in a faster and greater recovery of motor and memory functions as assessed by neurological severity score and object recognition tests, respectively. Moreover, DCS treatment of CHI mice led to a significant improvement of hippocampal long-term potentiation (LTP) in the CA1 region that was completely blunted in CHI control mice. However, DCS did not improve CHI induced impairment in synaptic glutamate release measured by paired pulse facilitation (PPF) ratio in hippocampal CA1 region. Finally, CHI-induced reduction of brain-derived neurotrophic factor (BDNF) was fully restored following DCS treatment. Since DCS is in clinical use for other indications, the present study offers a novel approach to treat human brain injury. PMID- 17351127 TI - 19F-NMR detection of lacZ gene expression via the enzymic hydrolysis of 2-fluoro 4-nitrophenyl beta-D-galactopyranoside in vivo in PC3 prostate tumor xenografts in the mouse. AB - Gene therapy shows promise for treating prostate cancer and has been evaluated in several clinical trials. A major challenge that remains is to establish a method for verifying transgene activity in situ. The lacZ gene encoding beta galactosidase historically has been the most popular reporter gene for molecular biology. We have designed a 19F NMR approach to reveal lacZ gene expression by assessing beta-galactosidase (beta-gal) activity in vivo. The substrate 2-fluoro 4-nitrophenyl beta-D-galactopyranoside (OFPNPG) is readily hydrolyzed by beta-gal with a corresponding decrease in the 19F-NMR signal from OFPNPG and the appearance of a new signal shifted 4-6 ppm upfield from the aglycone 2-fluoro-4 nitrophenol (OFPNP). We report proof of principle in cultures of PC3 prostate cancer cells using 19F NMR spectroscopy and 19F chemical shift imaging. More importantly, we demonstrate for the first time the ability to differentiate wild type and lacZ-expressing prostate tumor xenografts in mice using this approach. PMID- 17351128 TI - LAPSER1 is a putative cytokinetic tumor suppressor that shows the same centrosome and midbody subcellular localization pattern as p80 katanin. AB - Prostate cancer is one of the most common cancers in men, with more than 500,000 new worldwide cases reported annually, resulting in 200,000 deaths of mainly older men in developed countries. Existing treatments have not proved very effective in managing prostate cancer, and continuing efforts therefore are ongoing to explore novel targets and strategies for future therapies. LAPSER1 has been identified as a candidate tumor suppressor gene in prostate cancer, but its true functions remain unknown. We report here that LAPSER1 colocalizes to the centrosomes and midbodies in mitotic cells with gamma-tubulin, MKLP1, and p80 katanin, and is involved in cytokinesis. Moreover, RNAi-mediated disruption of LAPSER1, which is accompanied by the mislocalization of p80 katanin, results in malformation of the central spindle. Significantly, the enhanced expression of LAPSER1 induces binucleation and renders the cells resistant to oncogenic transformation. In cells transformed by the v-Fps oncogene, overexpressed LAPSER1 induces abortive cytokinesis, followed by mitotic catastrophe in a p80 katanin dependent manner. Cells that are rescued from this apoptotic pathway with Z-VAD fmk display karyokinesis. These results suggest that LAPSER1 participates in cytokinesis by interacting with p80 katanin, the disruption of which may potentially cause genetic instability and cancer. PMID- 17351129 TI - Adenovirus E4orf6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53. AB - The adenovirus protein E4orf6 targets p53 for polyubiquitination and proteasomal degradation and is known to form a complex with the Cul5-ElonginB-ElonginC E3 ubiquitin ligase. However, whether Cul5 is directly responsible for the E4orf6 mediated degradation of p53 remains unclear. By using a dominant-negative mutant of Cul5 and silencing Cul5 expression through RNA interference, we have now demonstrated that E4orf6-mediated p53 degradation requires Cul5. Furthermore, we have identified a lentiviral Vif-like BC-box motif in E4orf6 that is highly conserved among adenoviruses from multiple species. More importantly, we have shown that this Vif-like BC-box is essential for the recruitment of Cul5-ElonginB ElonginC E3 ubiquitin ligase by E4orf6 and is also required for E4orf6-mediated p53 degradation. E4orf6 selectively recruited Cul5 despite the lack of either a Cul5-box, which is used by cellular substrate receptors to recruit Cul5, or a newly identified HCCH zinc-binding motif, which is used by primate lentiviral Vif to recruit Cul5. Therefore, adenovirus E4orf6 molecules represent a novel family of viral BC-box proteins the cellular ancestor of which is as yet unknown. PMID- 17351130 TI - Evolution and multilevel optimization of the genetic code. AB - The discovery of the genetic code was one of the most important advances of modern biology. But there is more to a DNA code than protein sequence; DNA carries signals for splicing, localization, folding, and regulation that are often embedded within the protein-coding sequence. In this issue, Itzkovitz and Alon show that the specific 64-to-20 mapping found in the genetic code may have been optimized for permitting protein-coding regions to carry this extra information and suggest that this property may have evolved as a side benefit of selection to minimize the negative effects of frameshift errors. PMID- 17351131 TI - A palindrome-driven complex rearrangement of 22q11.2 and 8q24.1 elucidated using novel technologies. AB - Constitutional translocations at the same 22q11.21 low copy repeat B (LCR-B) breakpoint involved in the recurrent t(11;22) are relatively abundant. A novel 46,XY,t(8;22)(q24.13;q11.21) rearrangement was investigated to determine whether the recurrent LCR-B breakpoint is involved. Investigations demonstrated an inversion of the 3Mb region typically deleted in patients with the 22q11.2 deletion syndrome. The 22q11.21 inversion appears to be mediated by low copy repeats, and is presumed to have taken place prior to translocation with 8q24.13. Despite predictions based on inversions observed in other chromosomes harboring low copy repeats, this 22q11.2 inversion has not been observed previously. The current studies utilize novel laser microdissection and MLPA (multiplex ligation dependent probe amplification) approaches, as adjuncts to FISH, to map the breakpoints of the complex rearrangements of 22q11.21 and 8q24.21. The t(8;22) occurs between the recurrent site on 22q11.21 and an AT-rich site at 8q24.13, making it the fifth different chromosomal locus characterized at the nucleotide level engaged in a translocation with the unstable recurrent breakpoint at 22q11.21. Like the others, this breakpoint occurs at the center of a palindromic sequence. This sequence appears capable of forming a perfect 145 bp stem-loop. Remarkably, this site appears to have been involved in a previously reported t(3;8) occurring between 8q24.13 and FRA3B on 3p14.2. Further, the fragile site like nature of all of the breakpoint sites involved in translocations with the recurrent site on 22q11.21, suggests a mechanism based on delay of DNA replication in the initiation of these chromosomal rearrangements. PMID- 17351132 TI - Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicans. AB - Candida albicans is the most common fungal pathogen of humans. Frequently found as a commensal within the digestive tracts of healthy individuals, C. albicans is an opportunistic pathogen that causes a wide variety of clinical syndromes in immuno-compromised individuals. A comprehensive annotation of the C. albicans genome sequence was recently published. Because many C. albicans coding sequences are interrupted by introns, proper intron annotation is essential for the accurate definition of genes in this pathogen. Intron annotation is also important for identifying potential targets of splicing regulation, a common mechanism of gene control in eukaryotes. In this study, we report an improved annotation of C. albicans introns. In addition to correcting the existing intron annotations, 25% of which were incorrect, we have used novel computational and experimental approaches to identify new introns, bringing the total to 415, almost double the number previously known. Our identification methods focus primarily on intron features rather than protein-coding features, overcoming biases of traditional intron annotation methods. Introns are not randomly distributed in C. albicans, and are over-represented in genes involved in specific cellular processes, such as splicing, translation, and mitochondrial respiration. This nonrandom distribution suggests functional roles for these introns, and we demonstrate that splicing of two transcripts whose introns have unusual sequence features is responsive to environmental factors. PMID- 17351133 TI - Genome-wide identification of spliced introns using a tiling microarray. AB - The prediction of gene models from genome sequence remains an unsolved problem. One hallmark of eukaryotic gene structure is the presence of introns, which are spliced out of pre-mRNAs prior to translation. The excised introns are released in the form of lariats, which must be debranched prior to their turnover. In the yeast Saccharomyces cerevisiae, the absence of the debranching enzyme causes these lariat RNAs to accumulate. This accumulation allows a comparison of tiling array signals of RNA from the debranching mutant to the wild-type parent strain, and thus the identification of lariats on a genome-wide scale. This approach identified 141 of 272 known introns, confirmed three previously predicted introns, predicted four novel introns (of which two were experimentally confirmed), and led to the reannotation of four others. In many instances, signals from the tiling array delineated the 5' splice site and branchpoint site, confirming predicted gene structures. Nearly all introns that went undetected are present in mRNAs expressed at low levels. Overall, 97% of the significant probes could be attributed either to spliced introns or to genes up-regulated by deletion of the debranching enzyme. Because the debranching enzyme is conserved among eukaryotes, this approach could be generally applicable for the annotation of eukaryotic genes and the detection of novel and alternative splice forms. PMID- 17351134 TI - Recent human effective population size estimated from linkage disequilibrium. AB - Effective population size (N(e)) determines the amount of genetic variation, genetic drift, and linkage disequilibrium (LD) in populations. Here, we present the first genome-wide estimates of human effective population size from LD data. Chromosome-specific effective population size was estimated for all autosomes and the X chromosome from estimated LD between SNP pairs <100 kb apart. We account for variation in recombination rate by using coalescent-based estimates of fine scale recombination rate from one sample and correlating these with LD in an independent sample. Phase I of the HapMap project produced between 18 and 22 million SNP pairs in samples from four populations: Yoruba from Ibadan (YRI), Nigeria; Japanese from Tokyo (JPT); Han Chinese from Beijing (HCB); and residents from Utah with ancestry from northern and western Europe (CEU). For CEU, JPT, and HCB, the estimate of effective population size, adjusted for SNP ascertainment bias, was approximately 3100, whereas the estimate for the YRI was approximately 7500, consistent with the out-of-Africa theory of ancestral human population expansion and concurrent bottlenecks. We show that the decay in LD over distance between SNPs is consistent with recent population growth. The estimates of N(e) are lower than previously published estimates based on heterozygosity, possibly because they represent one or more bottlenecks in human population size that occurred approximately 10,000 to 200,000 years ago. PMID- 17351135 TI - Low copy repeats mediate distal chromosome 22q11.2 deletions: sequence analysis predicts breakpoint mechanisms. AB - Genomic disorders contribute significantly to genetic disease and, as detection methods improve, greater numbers are being defined. Paralogous low copy repeats (LCRs) mediate many of the chromosomal rearrangements that underlie these disorders, predisposing chromosomes to recombination errors. Deletions of proximal 22q11.2 comprise the most frequently occurring microdeletion syndrome, DiGeorge/Velocardiofacial syndrome (DGS/VCFS), in which most breakpoints have been localized to a 3 Mb region containing four large LCRs. Immediately distal to this region, there are another four related but smaller LCRs that have not been characterized extensively. We used paralog-specific primers and long-range PCR to clone, sequence, and examine the distal deletion breakpoints from two patients with de novo deletions mapping to these distal LCRs. Our results present definitive evidence of the direct involvement of LCRs in 22q11 deletions and map both breakpoints to the BCRL module, common to most 22q11 LCRs, suggesting a potential region for LCR-mediated rearrangement both in the distal LCRs and in the DGS interval. These are the first reported cases of distal 22q11 deletions in which breakpoints have been characterized at the nucleotide level within LCRs, confirming that distal 22q11 LCRs can and do mediate rearrangements leading to genomic disorders. PMID- 17351137 TI - Rats depend on habit memory for discrimination learning and retention. AB - We explored the circumstances in which rats engage either declarative memory (and the hippocampus) or habit memory (and the dorsal striatum). Rats with damage to the hippocampus or dorsal striatum were given three different two-choice discrimination tasks (odor, object, and pattern). These tasks differed in the number of trials required for learning (approximately 10, 60, and 220 trials). Dorsal striatum lesions impaired discrimination performance to a greater extent than hippocampal lesions. Strikingly, performance on the task learned most rapidly (the odor discrimination) was severely impaired by dorsal striatum lesions and entirely spared by hippocampal lesions. These findings suggest that discrimination learning in the rat is primarily supported by the dorsal striatum (and habit memory) and that rats engage a habit-based memory system even for a task that takes only a few trials to acquire. Considered together with related studies of humans and nonhuman primates, the findings suggest that different species will approach the same task in different ways. PMID- 17351136 TI - The influence of visual ability on learning and memory performance in 13 strains of mice. AB - We calculated visual ability in 13 strains of mice (129SI/Sv1mJ, A/J, AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, MOLF/EiJ, SJL/J, SM/J, and SPRET/EiJ) on visual detection, pattern discrimination, and visual acuity and tested these and other mice of the same strains in a behavioral test battery that evaluated visuo-spatial learning and memory, conditioned odor preference, and motor learning. Strain differences in visual acuity accounted for a significant proportion of the variance between strains in measures of learning and memory in the Morris water maze. Strain differences in motor learning performance were not influenced by visual ability. Conditioned odor preference was enhanced in mice with visual defects. These results indicate that visual ability must be accounted for when testing for strain differences in learning and memory in mice because differences in performance in many tasks may be due to visual deficits rather than differences in higher order cognitive functions. These results have significant implications for the search for the neural and genetic basis of learning and memory in mice. PMID- 17351138 TI - Medial auditory thalamic stimulation as a conditioned stimulus for eyeblink conditioning in rats. AB - The neural pathways that convey conditioned stimulus (CS) information to the cerebellum during eyeblink conditioning have not been fully delineated. It is well established that pontine mossy fiber inputs to the cerebellum convey CS related stimulation for different sensory modalities (e.g., auditory, visual, tactile). Less is known about the sources of sensory input to the pons that are important for eyeblink conditioning. The first experiment of the current study was designed to determine whether electrical stimulation of the medial auditory thalamic nuclei is a sufficient CS for establishing eyeblink conditioning in rats. The second experiment used anterograde and retrograde tract tracing techniques to assess neuroanatomical connections between the medial auditory thalamus and pontine nuclei. Stimulation of the medial auditory thalamus was a very effective CS for eyeblink conditioning in rats, and the medial auditory thalamus has direct ipsilateral projections to the pontine nuclei. The results suggest that the medial auditory thalamic nuclei and their projections to the pontine nuclei are components of the auditory CS pathway in eyeblink conditioning. PMID- 17351139 TI - Hormonal and monoamine signaling during reinforcement of hippocampal long-term potentiation and memory retrieval. AB - Recently it was shown that holeboard training can reinforce, i.e., transform early-LTP into late-LTP in the dentate gyrus during the initial formation of a long-term spatial reference memory in rats. The consolidation of LTP as well as of the reference memory was dependent on protein synthesis. We have now investigated the transmitter systems involved in this reinforcement and found that LTP-consolidation and memory retrieval were dependent on beta-adrenergic, dopaminergic, and mineralocorticoid receptor (MR) activation, whereas glucocorticoid receptors (GRs) were not involved. Blockade of the beta-adrenergic signaling pathway significantly increased the number of reference memory errors compared with MR and dopamine receptor inhibition. In addition, beta-adrenergic blockade impaired the working memory. Therefore, we suggest that beta-adrenergic receptor activation is the main signaling system required for the retrieval of spatial memory. In addition, other modulatory interactions such as dopaminergic as well as MR systems are involved. This result points to specific roles of different modulatory systems during the retrieval of specific components of spatial memory. The data provide evidence for similar integrative interactions between different signaling systems during cellular memory processes. PMID- 17351140 TI - Implicit probabilistic sequence learning is independent of explicit awareness. AB - Studies into interactions between explicit and implicit motor sequence learning have yielded mixed results. Some of these discrepancies have been attributed to difficulties in isolating implicit learning. In the present study, the effect of explicit knowledge on implicit learning was investigated using a modified version of the Alternating Serial Response Time (ASRT) task, a probabilistic sequence learning paradigm that yields continuous and relatively pure measures of implicit learning. Results revealed that implicit learning occurred to the same extent, whether or not subjects had explicit knowledge. Some evidence, however, indicated that explicit knowledge could interfere with the expression of implicit learning early in training. In addition, there were dissociations between learning measures, in that reaction time and accuracy were differentially affected by explicit knowledge. These findings indicate that implicit sequence learning occurs independently of explicit knowledge, and help to explain previous discrepant findings. PMID- 17351142 TI - Synapse specificity of long-term potentiation breaks down with aging. AB - Memory shows age-related decline. According to the current prevailing theoretical model, encoding of memories relies on modifications in the strength of the synapses connecting the different cells within a neuronal network. The selective increases in synaptic weight are thought to be biologically implemented by long term potentiation (LTP). Here, we report that tetanic stimulation of afferent fibers in slices from 12-mo-old mice triggers an LTP not restricted to the activated synapses. This phenomenon, which can be anticipated to hinder memory encoding, is suppressed by blocking either L-type Ca(++) channels or Ca(++) induced Ca(++) release, both well known to become disregulated with aging. PMID- 17351141 TI - Angiotensin-(1-7)-induced plasticity changes in the lateral amygdala are mediated by COX-2 and NO. AB - It is known from studies outside the brain that upon binding to its receptor, angiotensin-(1-7) elicits the release of prostanoids and nitric oxide (NO). Cyclooxygenase (COX) is a key enzyme that converts arachidonic acid to prostaglandins. Since there are no data available so far on the role of COX-2 in the amygdala, in a first step we demonstrated that the selective COX-2 inhibitor NS-398 significantly reduced the probability of long-term potentiation (LTP) induction in the lateral nucleus of the amygdala. Similarly, in COX-2(-/-) mice, LTP induced by external capsule (EC) stimulation was impaired. Second, we evaluated the action of angiotensin-(1-7) in the amygdala. In wild-type mice, angiotensin-(1-7) increased LTP. This LTP-enhancing effect of Ang-(1-7) was not observed in COX-2(+/-) mice. However, in COX-2(-/-) mice, Ang-(1-7) caused an enhancement of LTP similar to that in wild-type mice. The NO synthetase inhibitor L-NAME blocked this angiotensin-(1-7)-induced increase in LTP in COX-2(-/-) mice. Low-frequency stimulation of external capsule fibers did not cause long-term depression (LTD) in drug-free and angiotensin-(1-7)-treated brain slices in wild type mice. In contrast, in COX-2(-/-) mice, angiotensin-(1-7) caused stable LTD. Increasing NO concentration by the NO-donor SNAP also caused LTD in wild-type mice. Our study shows for the first time that LTP in the amygdala is dependent on COX-2 activity. Moreover, COX-2 is involved in the mediation of angiotensin-(1-7) effects on LTP. Finally, it is recognized that there is a molecular cross-talk between COX-2 and NO that may regulate synaptic plasticity. PMID- 17351143 TI - LTP induction modifies functional relationship among hippocampal neurons. AB - To obtain evidence linking long-term potentiation (LTP) and memory, we examined whether LTP induction modifies functional relationship among neurons in the rat hippocampus. In contrast to neurons in low-frequency stimulated or AP5-treated slices, LTP induction altered 'functional connectivity,' as defined by the degree of synchronous firing, among simultaneously recorded neurons in the CA3 region. Interestingly, functional connectivity changed bidirectionally so that the total sum of functional connectivity remained constant. These results demonstrate LTP induced changes in neuronal functional connectivity and suggest the existence of a normalization mechanism for the total sum of functional connectivity. PMID- 17351144 TI - Long-term memory for place learning is facilitated by expression of cAMP response element-binding protein in the dorsal hippocampus. AB - Extensive research has shown that the hippocampus is necessary for consolidation of long-term spatial memory in rodents. We reported previously that rats using a place strategy to solve a cross maze task showed sustained phosphorylation of hippocampus cyclic AMP response element-binding protein (CREB), a transcription factor implicated in long-term memory formation. In the current study, we used viral vector-mediated gene transfer to test the hypothesis that formation of long term memory for place learning can be facilitated by increasing levels of CREB in the dorsal hippocampus. Three days after intrahippocampus infusion, experimental (HSV-CREB) and control (HSV-LacZ; saline) rats were trained during a single session on a place task in a water cross maze. Rats were tested for memory 5 d later. Rats in all groups showed short-term memory, and there were no significant differences among treatment groups during acquisition. However, only HSV-CREB infused rats showed significant savings between training and test, while HSV-LacZ and saline-treated rats did not. Quantitative Western blotting confirmed that levels of dorsal hippocampus CREB were increased during training in rats infused with HSV-CREB in comparisons with controls. The present results show that formation of long-term memory can be facilitated by increasing levels of hippocampus CREB protein. PMID- 17351145 TI - Context preexposure prevents forgetting of a contextual fear memory: implication for regional changes in brain activation patterns associated with recent and remote memory tests. AB - Contextual fear conditioning was maintained over a 15-day retention interval suggesting no forgetting of the conditioning experience. However, a more subtle generalization test revealed that, as the retention interval increased, rats showed enhanced generalized fear to an altered context. Preexposure to the training context prior to conditioning, however, prevented this enhanced generalized fear from developing. These results support the hypothesis that the memory representation of the context degrades as the memory ages and is responsible for enhanced generalization. The implications of these results for systems consolidation versus forgetting interpretations of regional changes in neural activation patterns that occur as memories age are discussed. PMID- 17351146 TI - Lexico-semantic structure and the word-frequency effect in recognition memory. AB - The word-frequency effect (WFE) in recognition memory refers to the finding that more rare words are better recognized than more common words. We demonstrate that a familiarity-discrimination model operating on data from a semantic word association space yields a robust WFE in data on both hit rates and false-alarm rates. Our modeling results suggest that word frequency is encoded in the semantic structure of language, and that this encoding contributes to the WFE observed in item-recognition experiments. PMID- 17351147 TI - Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. AB - Muscle protein metabolism is resistant to insulin's anabolic effect in healthy older subjects. This is associated with reduced insulin vasodilation. We hypothesized that aerobic exercise restores muscle protein anabolism in response to insulin by improving vasodilation in older subjects. We measured blood flow, endothelin-1, Akt/mammalian target of rapamycin (mTOR) signaling, and muscle protein kinetics in response to physiological local hyperinsulinemia in two groups of older subjects following a bout of aerobic exercise (EX group: aged 70 +/- 2 years; 45-min treadmill walk, 70% heart rate max) or rest (CTRL group: aged 68 +/- 1 years). Baseline endothelin-1 was lower and blood flow tended to be higher in the EX group, but protein kinetics was not different between groups. Insulin decreased endothelin-1 (P < 0.05) in both groups, but endothelin-1 remained higher in the CTRL group (P < 0.05) and blood flow increased only in the EX group (EX group: 3.8 +/- 0.7 to 5.3 +/- 0.8; CTRL group: 2.5 +/- 0.2 to 2.6 +/ 0.2 ml x min(-1) x 100 ml leg(-1)). Insulin improved Akt phosphorylation in the EX group and increased mTOR/S6 kinase 1 phosphorylation and muscle protein synthesis (EX group: 49 +/- 11 to 89 +/- 23; CTRL group: 58 +/- 8 to 57 +/- 12 nmol x min(-1) x 100 ml leg(-1)) in the EX group only (P < 0.05). Because breakdown did not change, net muscle protein balance became positive only in the EX group (P < 0.05). In conclusion, a bout of aerobic exercise restores the anabolic response of muscle proteins to insulin by improving endothelial function and Akt/mTOR signaling in older subjects. PMID- 17351148 TI - A functional variant of the adipocyte glycerol channel aquaporin 7 gene is associated with obesity and related metabolic abnormalities. AB - Aquaporin 7 (AQP7), the gateway protein controlling glycerol release, has recently emerged as a modulator of adipocyte metabolism. AQP7 knockout mice develop obesity and hyperglycemia. The contribution of AQP7 to these abnormalities in humans is unknown. We examined whether common single nucleotide polymorphisms (SNPs) in the AQP7 gene modulate the risk of obesity and related abnormalities. Among several SNPs we identified, A-953G in the AQP7 promoter was associated with type 2 diabetes in 977 (530 female/447 male) Caucasians: odds ratio for XG (i.e., AG+GG) versus AA individuals was 1.36 (95% CI 1.01-1.84), P = 0.04. This finding was entirely due to the association among females (1.8 [1.2 2.6], P = 0.004), which was no longer significant when adjusted for BMI. In fact, BMI was higher in XG than in AA females (30.8 +/- 6.6 vs. 28.9 +/- 5.2, P = 0.002). This association was confirmed in independent case-control study (n = 299 female subjects) for morbid obesity (1.66 [1.01-2.74], P = 0.04). Luciferase and mobility shift assays showed that, compared with -953A, the -953G promoter had reduced transcriptional activity (P = 0.001) and impaired ability to bind CCAAT/enhancer binding protein (C/EBP)beta transcription factor (P = 0.01). Finally, AQP7 expression in adipose tissue decreased from AA to AG to GG individuals (P = 0.036). These data strongly suggest that AQP7 downregulation is pathogenic for obesity and/or type 2 diabetes. PMID- 17351150 TI - Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. AB - We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3 content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria. Respiration was normalized to citrate synthase activity (mitochondrial content) in isolated mitochondria. Maximal ADP-stimulated respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese subjects (all P < 0.05). There were no differences in respiration with palmitoyl-l-carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between the groups. In the whole group, state 3 respiration with pyruvate plus malate and respiration through ETC were negatively associated with A1C, and the proportion of type 2X fibers correlated with markers of insulin resistance (P < 0.05). In conclusion, we provide evidence for a functional impairment in mitochondrial respiration and increased amount of type 2X fibers in muscle of type 2 diabetic patients. These alterations may contribute to the development of type 2 diabetes in humans with obesity. PMID- 17351151 TI - Proteomics identification of sorting nexin 27 as a diacylglycerol kinase zeta associated protein: new diacylglycerol kinase roles in endocytic recycling. AB - Diacylglycerol kinase zeta is a member of the diacylglycerol kinase family of enzymes, which generate phosphatidic acid through diacylglycerol phosphorylation. In addition to the catalytic and cysteine-rich domains found in all diacylglycerol kinases, diacylglycerol kinase zeta has a MARCKS domain as well as a C-terminal region containing four ankyrin repeats and a PDZ-binding motif. Previous reports demonstrated that diacylglycerol kinase zeta interaction with several proteins is an important mechanism for modulating the localization and activity of this enzyme. Here we used a proteomics approach to search for novel diacylglycerol kinase zeta-interacting proteins and identified sorting nexin 27 (SNX27), a recently described member of a protein family involved in intracellular trafficking, which has a PDZ domain in addition to the phox homology domain characteristic of SNX proteins. Co-immunoprecipitation studies and two-hybrid analysis confirmed physical, PDZ-dependent association between SNX27 and diacylglycerol kinase zeta. Because diacylglycerol kinase zeta is expressed abundantly in T lymphocytes, we characterized SNX27 expression and subcellular localization in these cells. SNX27 co-localized with transferrin receptor-positive vesicles, pointing to its participation in T cell endocytic recycling. Expression of deletion mutants revealed that in addition to the phox homology domain the SNX27 PDZ domain contributed to vesicle localization of this protein, suggesting that interaction with diacylglycerol kinase zeta regulates SNX27 localization. Analysis of cells with RNA interference-mediated knockdown of diacylglycerol kinase zeta showed accelerated transferrin receptor exit from the lymphocyte endocytic recycling compartment back to the plasma membrane, further confirming diacylglycerol kinase zeta-dependent control of vesicle trafficking. These data support a previously unreported role for diacylglycerol kinase zeta in the modulation of membrane trafficking, which may also help to define SNX27 function. PMID- 17351152 TI - The relationship between arterial elasticity and metabolic syndrome features. AB - The purpose of this study was to examine the effects of metabolic syndrome (MS) features on arterial elasticity of the large and small arteries in apparently healthy adults, to examine the effect of clustered features of MS, and to determine which features are most predictive of large and small artery elasticity. The subjects for this study consisted of 126 men and women, age 45 years and older. The subjects rested supine while pulse contour analysis was measured from the radial artery by using an HDI/Pulsewave CR-2000 instrument (Hypertension Diagnostic, Inc) to assess arterial elasticity in the large and small arteries. Medical history was obtained along with body mass index, waist circumference, body surface area, and blood pressure. Large artery elasticity was lower (p = 0.002) in subjects with hypertension (12.7 -/+ 4.3 mL/mm Hg x 10) than in those with normotension (15.0 -/+ 4.2 mL/mm Hg x 10; mean -/+ SD), and small artery elasticity was lower (p = 0.001) as well (3.9 -/+2.3 mL/mm Hg x 100 vs 5.3 -/+ 2.5 mL/mm Hg x 100). Large artery elasticity was lower (p = 0.02) in obese subjects (12.2 -/+ 4.9 mL/mm Hg x 10) than in nonobese subjects (14.2 -/+ 4.5 mL/mm Hg x 10), and large artery elasticity was lower (p = 0.04) in subjects with abdominal obesity (12.2 -/+ 4.5 mL/mm Hg x 10) than in those without (14.5 -/+ 4.8 mL/mm Hg x 10). Large artery elasticity decreased as the number of features of MS increased (p < 0.01). Multiple regression showed that body mass index and the presence of hypertension were predictors of large artery elasticity (R = 0.61, R2 = 0.37, p = 0.003, SEE = 3.60 mL/mm Hg x 10), and hypertension was a predictor of small artery elasticity (R = 0.53, R2 = 0.28, p = 0.001, SEE = 2.12 mL/mm Hg x 100). Hypertension and obesity are the features of MS that are most predictive of impairment in large and small artery elasticity in apparently healthy middle-aged and older adults. Furthermore, impairment in large artery elasticity is more evident in subjects with at least three features of MS. PMID- 17351153 TI - Arterial stiffness: determinants and relationship to the metabolic syndrome. AB - This study aimed to investigate independent determinants of arterial stiffness and evaluate the association of arterial stiffness with the presence of metabolic syndrome (MS). Demographic characteristics, hemodynamic parameters, and cardiovascular (CV) risk factors were assessed in Greek food industry employees with no history of diabetes or CV disease in order to isolate multiple correlates of arterial stiffness as assessed by pulse wave velocity (PWV). Subsequently, logistic regression analysis was performed using as end point the presence of MS, defined according to the National Cholesterol Education Program. Data from 424 participants (mean age 45.3 -/+ 15.5 years, 298 [70.3%] males, average PWV 8.5 /+ 3.6 m/s) were analyzed. PWV was higher in men (8.8 -/+ 3.1 m/s) compared to women (7.7 -/+ 2.9 m/s, p < 0.01). Age, systolic blood pressure, and heart rate were isolated as multivariate determinants of PWV (adjusted R2 0.511 [p < 0.0001] in men and 0.538 [p < 0.0001] in women). The overall prevalence of the MS was 14.6%, being similar in both genders. Four variables were shown to be independent predictors of the presence of MS: waist circumference >102 cm (men)/88 cm (women) (OR 8.6, [95% CI 2.8, 20.6], p < 0.001), insulin resistance (homeostasis model assessment >4) (6.3, [2.1, 17.6], p < 0.001), total cholesterol >240 mg/dL (5.5, [1.7, 12.4], p < 0.01), PWV >9 m/s (4.1, [1.5, 9.9], p < 0.01). High PWV, which was found to be mostly determined by advanced age, elevated systolic BP, and accelerated heart rate, appeared to exhibit a strong independent association with the presence of MS together with adiposity and insulin resistance. This index should be considered as a useful marker for CV risk stratification. PMID- 17351154 TI - Impact of the metabolic syndrome on atrial size in patients with new-onset atrial fibrillation. AB - Atrial fibrillation (AF) is the most common arrhythmia, and it is strongly related to atrial enlargement. Metabolic syndrome (MetSyn) is associated with increased cardiovascular morbility and mortality. However, the impact of the MetSyn on cardiac arrhythmias is poorly elucidated. The aim of this study was to compare atrial dimensions in patients suffering from nonvalvular paroxysmal AF, with and without MetSyn, trying to identify structural differences that could favor the occurrence of this arrhythmia. The study population consisted of 60 patients who presented with at least 1 episode of paroxysmal AF. From these, 26 patients fulfilled the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) definition of MetSyn, while the remaining 34 patients did not. Left atrial size was assessed by 2-dimensional echocardiography. Patients with MetSyn had a mean atrial size of 46.2 -/+ 4.3 mm and those without MetSyn had a mean atrial size of 41.6 -/+ 1.9 mm, p < 0.011. MetSyn may favor the occurrence of paroxysmal AF by increasing atrial size. This concept deserves more research. PMID- 17351155 TI - Short-term administration of orlistat reduced daytime triglyceridemia in obese women with the metabolic syndrome. AB - The objective of this prospective, controlled, randomized study was to evaluate the effect of orlistat administration for 10 days on daytime capillary triglyceridemia in obese women with metabolic syndrome (MetSyn). Thirty-two obese, nondiabetic women with MetSyn were evaluated. The presence of MetSyn was defined according to the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) criteria. Patients were randomized into 2 similar groups: group A (orlistat), mean age 50.1 -/+ 8.2 years, received a low-calorie diet combined with orlistat 120 mg tid for 10 days and group B (control), mean age 51.2 -/+ 9.1 years, received only the low-calorie diet for the same period of time. Anthropometric, lipids, and parameters of insulin resistance were measured before and after 10 days of intervention. Capillary triglycerides (TGc) were measured at 6 different time points during the day and daytime triglyceridemia was expressed as area under the curve of TGc (AUC-TGc). Most anthropometric measurements (body weight, body mass index, waist circumference, and percentage of fat mass) and most metabolic parameters (total cholesterol [TC], fasting venous triglycerides [TGfv], high-density lipoprotein cholesterol [HDL-C] levels, fasting glucose [FG], fasting insulin [FI], and homeostasis model for assessment [HOMA] for insulin resistance index) decreased significantly in both groups, while waist-to-hip ratio (WHR) and systolic (SBP) and diastolic blood pressure (DBP) did not change significantly in both groups and low-density lipoprotein cholesterol (LDL-C) levels decreased only in the orlistat group. Following minimal weight loss, TGc at most time points and AUC-TGc were significantly reduced only in group A. In group A, AUG-TGc decreased by 17% from 36.4 -/+11.8 to 30.2 -/+9.9 mmol/Lxh(-1) (p < 0.001), and this reduction was significantly greater compared with the control group (p < 0.05) and remained significant after percentage of weight loss was taken into account. This decrease of AUC-TGc significantly correlated with the decrease of HOMA index (p < 0.05, r = 0.39) and the decrease of TGfv (p < 0.001, r = 0.62). The tolerability of orlistat was very good and side effects were transient and of minimal intensity. In conclusion, short-term administration of orlistat significantly reduced daytime triglyceridemia in obese, nondiabetic women with MetSyn. This reduction could offer cardiovascular benefits in these high-risk patients. Long-term studies with more patients are needed to reach definite conclusions. PMID- 17351156 TI - The open artery hypothesis: beneficial effects and long-term prognostic importance of patency of the infarct-related coronary artery. AB - There seem to be additional mechanisms of benefit in patients receiving late reperfusion therapy in a time when the opportunity for myocardial salvage has been missed. Previous studies have demonstrated that the restoration of blood flow in the infarct-related coronary artery in patients with acute myocardial infarction improves left ventricular function and reduces mortality. Initially, it was thought that survival was improved because viable myocardium was salvaged. However, data obtained over the past several years have suggested that the restoration of antegrade flow in the infarct-related artery may improve survival via a mechanism independent of the influence on left ventricular function. Clinical interest in the open artery hypothesis has recently resurfaced owing to a substantial improvement in technical aspects of percutaneous coronary interventions (PCI). Observational data suggest a role for late intervention as safer and more effective mechanical reperfusion practices have emerged. Long-term clinical benefits have been shown from balloon angioplasty late after myocardial infarction (MI). Therefore, patients with failed thrombolysis or those with late presenting MI may still benefit from PCI by mechanisms independent of myocardial salvage. There is accumulative evidence on this matter. Possible mechanisms include reduction of ventricular remodeling, diminished ventricular instability reducing the incidence of arrhythmias, and provision of collaterals to other territories in the event of further coronary artery occlusion. However, caution must be exercised in interpreting the results of studies examining the open artery hypothesis. This hypothesis can be tested in its purest sense in animal experiments; however, the clinical situation is much more complex. Patients may have acute-on-chronic coronary artery occlusion in the presence of multivessel disease and well-developed collateral channels. The pattern of necrosis may also be different with areas of necrosis separated by islands of ischemic, stunned, hibernating, or normal cells. Therefore, the patency of the infarct-related coronary artery in single or multivessel disease days to weeks after infarction markedly influences long-term prognosis unrelated to improvement of left ventricular function. Current technology has made it feasible to open and maintain patency of most occluded infarct-related arteries. However, the hypothesis that late mechanical reperfusion in patients with asymptomatic occluded infarct-related artery will improve long-term clinical outcomes remains to be proved and is currently being tested in a large randomized trial. PMID- 17351157 TI - Role of novel mediators of inflammation in left ventricular remodeling in patients with acute myocardial infarction: do they affect the outcome of patients? AB - Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is a major mechanism for cardiovascular death and disability. A significant number of post-MI patients develop progressive left ventricular enlargement and heart failure and many require heart transplantation and ventricular assist devices. Understanding of the basic mechanisms regulating the reaction to injury is crucial for the development of site-specific cell biological strategies of intervention to both reduce injury and promote repair. To determine whether there are new inflammatory markers having a role in structural remodeling after AMI in patients who applied to the emergency department of this hospital with severe chest pain at the first 12 hours, the authors measured the levels of C-reactive protein (CRP), macrophage colony-stimulating factor (M-CSF) and interleukin-3 (IL 3) in patients with AMI at hospital admission and on day 5. They measured plasma CRP concentrations by using highly sensitive CRP reagent with the immunonephelometric method, and plasma M-CSF and IL-3 concentrations with the help of a commercial enzyme-linked immunoassay test in 30 patients with AMI. Mean plasma CRP, M-CSF, and IL-3 concentrations at admission to the hospital were significantly higher than those on day 5 (5.0 -/+ 3.1 mg/dL, 119.4 -/+ 103.6 pg/mL, and 155.1 -/+ 83.4 ng/mL, respectively, p < 0.001 for each value). CRP, M CSF, and IL-3 were all increased in patients with AMI. These findings suggest that these are new inflammatory markers, which may have important roles in LV remodeling after AMI. PMID- 17351158 TI - Effects of statins on restenosis after coronary stent implantation. AB - Experimental data and preliminary clinical studies suggest that lipid-lowering drugs might have a beneficial effect on restenosis after coronary angioplasty. Recently, statins have been focused on prevention of restenosis after coronary stent implantation. However, their benefit has not yet been established. The authors studied the effects of statins on stent restenosis. We compared retrospectively the quantitative coronary angiographic (QCA) variables between 62 dyslipidemic patients treated with statins (pravastatin or fluvastatin) and 62 normolipidemic patients, as a control, treated without statins after undergoing successful coronary stent implantation with 6-month follow-up angiography from May 1999 to December 2002. Major cardiac events were about the same in both groups. Each of the QCA variables before and immediately after coronary stenting was similar in the 2 groups. At follow-up angiography, however, minimal lumen diameter (MLD) (2.12 -/+ 0.73 vs 1.78 -/+ 0.7; p < 0.01) was larger in the statin group than in the normolipidemia group. Both restenosis rate (15% vs 31%; p = 0.05) and target lesion revascularization rate (10% vs 24%; p = 0.05) were lower in the statin group than in the normolipidemia group. Statin reduced restenosis rate. The efficacy of statins appears to be dependent on their pleiotropic effects on vascular wall rather than on lipid-lowering effects. PMID- 17351159 TI - Comparison of clinical characteristics of acute myocardial infarction in aborigines and nonaborigines in Taitung area of Taiwan. AB - This study aims to examine the correlation between acute myocardial infarction and various risk factors in eastern Taiwan as well as compare the manifestations of this serious disorder in nonaborigine and aborigine populations in the region. We collected 440 consecutive patients (308 nonaborigines and 132 aborigines) who were diagnosed with acute myocardial infarction (AMI) at the Mackay Memorial Hospital, Taitung Branch, between the years 1994 and 2001. Analysis showed that AMI was more prevalent in nonaborigines than in aborigines (0.021 -/+ 0.009% vs 0.011 -/+ 0.009%, p = 0.02). In term of gender, as a whole or within each ethnic group, AMI was more predominant in men than in women (as a whole, 70%; nonaborigines, 73%; aborigines, 63%; nonaborigines vs aborigines p = 0.03), and nonaborigines had more male patients. Regarding in-hospital mortality, the distribution of age (aborigine 68.2 -/+ 13.1 vs nonaborigine 73.5 -/+10.4, p = 0.02) and percentage of smokers (aborigine 15% vs nonaborigine 32%, p = 0.05) were different between the ethnic groups. Significant risk factors as a whole included the age, total cholesterol, uric acid, and the Killip Class of AMI. Multiple regression analysis showed that diabetes, age > or = 70 years, uric acid > or = 9.0 mg/dL, and Killip class 3 or 4 had relative risk of 1.81, 2.08, 2.89, and 1.63, respectively. However, mortality rate was not affected by ethnicity. PMID- 17351160 TI - Effects of heart rate on brachial-ankle pulse wave velocity and ankle-brachial pressure index in patients without significant organic heart disease. AB - This study evaluated the effects of heart rate (HR) on brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI). Thirty-two patients without significant organic heart disease underwent elective cardiac catheterization or electrophysiologic study, and were then enrolled in right atrial pacing (RAP; 11 men, 9 women; aged 48 -/+ 15 years) or right ventricular pacing (RVP; 6 men, 6 women, aged 45 -/+ 13 years) studies. Three different HR levels (90, 100, and 110 beats per minute) were paced in random order. By stepwise, multiple linear regression analysis, age, systolic blood pressure (SBP), and pulse pressure (PP) correlated positively with baseline baPWV. In the RAP group, as HR increased, baPWV and left brachial diastolic blood pressure increased significantly (p < or = 0.015), while ABI, left ankle SBP, left brachial PP, and left ankle PP decreased significantly (p < or = 0.013). In the RVP group, as HR increased, baPWV also increased significantly (p = 0.001), while ABI, left ankle SBP, and PP decreased significantly (p < or = 0.034). Values of baPWV and ABI may be influenced by HR in young and middle-aged patients without significant organic heart disease. When these values are used to evaluate and follow up cardiovascular risk in patients, HR changes should be considered. PMID- 17351161 TI - Thromboangiitis obliterans (Buerger's disease): searching for a therapeutic strategy. AB - Treatment of thromboangiitis obliterans (Buerger's disease) includes both surgical and nonsurgical approaches, or a combination of both. A definite therapeutic approach has not yet been set. This article reviews the proposed therapeutic strategies and considers the advantages and disadvantages of each treatment. Cessation of smoking seems to be the only globally accepted therapeutic measure to prevent disease progression. A number of promising novel therapeutic strategies may prove useful for the treatment of this physically and socially mutilating disease. PMID- 17351162 TI - Coagulation, fibrinolytic system activation and endothelial dysfunction in patients with mitral stenosis and sinus rhythm. AB - Anticoagulation treatment can prevent systemic embolism in patients with mitral stenosis (MS) and atrial fibrillation (AF), but this treatment is under debate if patients are in sinus rhythm. The authors aimed to determine the hemostatic changes in patients with MS and sinus rhythm. Forty-six patients (28 in sinus rhythm and 18 in AF) with mitral stenosis were enrolled in this study. They studied systemic venous fibrinogen, D-dimer, antithrombin-III, tissue plasminogen activator (tPA), plasminogen activator inhibitor-I (PAI-I), von Willebrand factor (vWF), and platelet factor 4 (PF 4) in these patients. The patients were first classified according to their rhythm as sinusal and AF, and then according to the presence of left atrial spontaneous echo contrast (LASEC). Fibrinogen, D-dimer, antithrombin-III, vWF, and PF 4 levels were significantly greater in patients with MS and sinus rhythm or atrial fibrillation compared to the control group (p < 0.05). Whether the rhythm was sinus or AF, fibrinogen, D-dimer, antithrombin III, vWF, and PF 4 levels were significantly higher in patients with LASEC than in the control group (p < 0.05). Only PF 4 was higher in the AF group than in those with sinus rhythm (p < 0.05). As to plasminogen activator and PAI-I levels, only tissue plasminogen activator levels were found to be higher in the AF group than in those with sinus rhythm and the control group (p < 0.05). In patients with mitral stenosis and sinus rhythm, if LASEC is present, coagulation activation, platelet activation, and endothelial dysfunction are similar in patients with AF, and anticoagulation should be considered in these patients. PMID- 17351163 TI - Wine, diet, and arterial hypertension. AB - Hypertension is one of the leading causes of death in developed countries, and the number of prehypertensive patients is increasing. The beneficial effects of moderate wine consumption on cardiovascular diseases have been demonstrated, along with the healthy influence of a Mediterranean dietary pattern. The association of these 2 factors on hypertension and its complications is considered here. As wine polyphenols exert a vasorelaxing action, they might positively influence the hemodynamic situation of these patients. These effects could be enhanced by dietary constituents, such as garlic, onions, and olive oil, which are widely employed in Mediterranean cooking. By evaluating many studies performed in animal models and in humans, the authors conclude that moderate wine consumption, if associated with a healthy dietary pattern, such as the Mediterranean one, could help hypertensive patients to ameliorate their arterial pressure and quality of life by reducing cardiovascular morbidity and mortality rates. PMID- 17351164 TI - P-wave durations in patients experiencing atrial fibrillation during exercise testing. AB - Augmented sympathoadrenal activity during exercise may contribute to occurrence of various arrhythmias including atrial fibrillation (AF). The prolongation of intraatrial and interatrial conduction times and inhomogeneous propagation of sinus impulses are well-known characteristics of the atrium prone to fibrillate and are evaluated by maximum P-wave duration (P max), P-wave dispersion (PWD). To show the increased P max and PWD values in patients experiencing AF during exercise testing and the role of beta blockade on treatment of exercise-induced AF, 22 of these patients were compared with a control group consisting of 41 patients without AF attacks. P max (p = 0.001) and PWD (p = 0.001) values were significantly higher in patients with AF compared to those without AF. The development of AF during exercise testing was found to be positively correlated with P max (r = 0.87, p < 0.001), PWD (r = 0.83, p = 0.001), and work load (r = 0.34, p = 0.002) and negatively correlated with ejection fraction (r = -0.26, p=0.02). After the treatment with beta-blocking agents for 2 weeks, the decrease in P max and PWD values was accompanied by a much lower prevalence of exercise induced AF. Consequently, the patients with AF had greater P max and PWD values compared to control subjects, and these simple parameters were well correlated with the occurrence of AF during exercise testing. Furthermore, treatment of these patients with beta blockers would appear to decrease the recurrence of exercise-induced AF and to be associated with a decrease in P-wave durations. PMID- 17351165 TI - The effect of ephedra and high fat dieting: a cause for concern! A case report. AB - The increased incidence of obesity in the world has resulted in more and more people attempting to lose weight through a variety of diets. Many of these diets employ caloric reduction through the elimination of certain food groups. These diets may initially be associated with weight loss (including water weight) but follow up reports of these diets show high drop out rates, proinflammatory changes which can precipitate heart disease and weight gain following cessation of these diets. Efforts to use prescription anorexic medications have been associated with valvular disease and other health concerns. Dissatisfaction with the medical community and a subsequent increase in the availability of information on the Internet, are only two of the reasons why people are looking at alternative medicine to assist with health care issues. This includes the use of herbal supplements for appetite suppression. A review of the literature reveals several problems with some of these supplements, including Ephedra. Potentially serious adverse effects include dysrhythmias, heart failure, myocardial infarction, changes in blood pressure, and death have occurred. Unfortunately, one half of all patients experiencing a myocardial infarction have total cholesterol levels below 150 mg/dL and/or no prior cardiac symptoms. This means that the development of inflammatory changes which can precipitate myocardial infarction may go unnoticed by conventional testing and unless markers of inflammation and coronary perfusion are looked for, changes which can precipitate myocardial infarction may go unnoticed until cardiac injury occurs. The following case presentation shows how an individual with exertional dyspnea and concerned about her weight was affected by both the ingestion of a low carbohydrate diet and ephedra. PMID- 17351166 TI - A sequential approach to the management of a massive intracoronary thrombus in ST elevation myocardial infarction: a case report. AB - Thrombus-laden coronary lesions present a particular challenge to the interventional cardiologist. Despite the development of multiple strategies to attack this problem, lesions with angio-graphically visible thrombus still carry a high risk of complications when coronary intervention is attempted. The authors present a case of acute inferior ST elevation myocardial infarction with a massive thrombus in an ectatic right coronary artery. Sequential treatment with intra-coronary glycoprotein IIb/IIIa inhibitor, rheolytic thrombectomy with 2 different-sized catheters, and transcatheter thrombus aspiration with a Pronto aspiration catheter was required to achieve a satisfactory result. This case illustrates the potential benefit of combining various mechanical strategies to treat intracoronary thrombus. PMID- 17351167 TI - Simultaneous multivessel coronary spasm causing acute myocardial infarction: a case report. AB - Spontaneous simultaneous multivessel coronary artery spasm in patients with acute myocardial infarction (AMI) is uncommon. A 79-year-old Japanese man was transferred to this hospital because of severe prolonged chest pain and faintness. Left coronary angiography revealed total occlusion of the left anterior descending and the left circumflex coronary arteries. Moreover, right coronary angiography revealed 99% stenosis of the right coronary artery. After intracoronary administration of nicorandil, left coronary artery and right coronary artery angiography revealed no organic stenosis or thrombus. This is the first report in which simultaneous 3-vessel spasm was documented by emergency angiography in AMI. PMID- 17351168 TI - Bilateral coronary artery fistulas communicating with main pulmonary artery and left ventricle: case report. AB - Coronary artery fistula is an uncommon congenital malformation that generally drains into the main pulmonary artery or the right side of the heart. This is a case report on bilateral coronary artery fistulas communicating with the main pulmonary artery and the left ventricle. A 65-year-old woman was investigated for recurrent chest pain. Coronary angiography revealed this anomalous coronary artery connection without evidence of atherosclerotic coronary artery disease. The rarity of coronary artery fistulas involving both the main pulmonary artery and the left ventricle is emphasized. PMID- 17351169 TI - Automatic implantable cardioverter defibrillator for the treatment of ventricular fibrillation following coronary artery spasm: a case report. AB - Coronary artery spasm is an infrequently recognized condition that causes Prinzmetal's angina and specific electrocardiographic changes. A 50-year-old man who suffered a spontaneously aborted acute inferior myocardial infarction is presented. He underwent cardiac catheterization, which initially showed a normal coronary artery. The coronary angiogram was repeated shortly after a second presentation of acute coronary syndrome and ventricular fibrillation. Coronary spasm of very proximal right coronary artery was present, which was reversed completely with intracoronary nitroglycerin. The spasm segment was first stented. Subsequently, an automatic implantable cardioverter defibrillator was inserted because of the uncertainty of future spasm recurrence. The patient was discharged with oral isosorbide dinitrate and Amlodipine. In further follow-up, the patient had two separate shocks within 4 months of implantation. Ventricular fibrillation was the trigger for the shock therapy in both occasions. PMID- 17351170 TI - Swallow syncope in a patient with esophageal stenosis caused by an ascending aorta aneurysm: differential diagnosis from postprandial hypotension: a case report. AB - Swallow syncope is usually caused by organic or functional disorders of the esophagus due to abnormal vasovagal reflex. In elderly patients this situation could be confused with postprandial hypotension. We present a case of an elderly patient who presented with swallow syncope that was caused by a waist in the midportion of esophagus induced by an ascending aorta aneurysm. PMID- 17351172 TI - Orthovoltage radiation and weekly low dose of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs. AB - The efficacy and toxicity of orthovoltage radiation therapy and concurrent low doses of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs was investigated retrospectively. The 39 dogs had 40 soft tissue sarcomas and received 51 Gy orthovoltage radiation in 17 daily 3 Gy fractions; they also received 10 mg/m(2) doxorubicin once a week administered intravenously one hour before the dose of radiation. The median follow-up time was 910 days. The tumours recurred locally in seven of the dogs, in five of them within the radiation field; the median time to their recurrence was 213 days (range 63 to 555 days). Six of the dogs developed a distant metastasis after a median time of 276 days (range eight to 826 days). The one-year and two- to four year tumour control rates were 84 per cent and 81 per cent, respectively, and the one-, two- and three- to four-year survival rates were 85 per cent, 79 per cent and 72 per cent, respectively. Tumours with a mitotic rate of more than 9 per 10 high-power fields were significantly more likely to recur, and the dogs with such tumours survived for significantly shorter periods. PMID- 17351173 TI - Retrospective study of noroviruses in samples of diarrhoea from cattle, using the Veterinary Laboratories Agency's Farmfile database. AB - A collaborative study was undertaken by the Veterinary Laboratories Agency (vla) and the Royal Veterinary College (rvc) to determine the prevalence of bovine noroviruses in cattle with diarrhoea. Samples of bovine diarrhoea were provided by the vla from routine diagnostic submissions and a reverse transcription-pcr was used by the rvc to detect the viruses. Epidemiological information about the samples was provided retrospectively by the Farmfile database. Noroviruses were detected in 44 (11 per cent) of the 398 samples tested, and Farmfile data were used to investigate the differences between the positive and negative animals. PMID- 17351174 TI - Lancefield group B and C streptococci in East African camels (Camelus dromedarius). AB - Seventeen Lancefield group C streptococci (13 Streptococcus equi zooepidemicus and four Streptococcus dysgalactiae equisimilis) and 185 Lancefield group B streptococci (Streptococcus agalactiae) were isolated from camels (Camelus dromedarius) in Kenya and Somalia; 59 of the isolates were from healthy nasopharynx, vaginal and rectal mucosa and from non-abscessed lymph nodes, and the other 143 isolates were from clinical infections of the respiratory tract, tick bite lesions, abscessed lymph nodes, abscesses and other purulent skin lesions, periarthritis and arthritis, puerperal infection and gingivitis. The role of Lancefield group B and C streptococci as commensals and common opportunistic pathogens in East African camels is described. PMID- 17351175 TI - PrP genotypes in a pedigree flock of Santa Ines sheep. PMID- 17351176 TI - Streptococcus bovis biotype I meningoencephalitis in an alpaca (Lama pacos) cria. PMID- 17351177 TI - Relative concentrations of progesterone and estradiol-17beta in blood serum, whole milk, skimmed milk and milk whey of Holstein cows. PMID- 17351178 TI - Bilateral thrombosis of the brachial artery in an adult horse. PMID- 17351179 TI - Prevention and control of avian influenza: the need for a paradigm shift in pandemic influenza preparedness. AB - Avian influenza presents both challenges and opportunities to leaders around the world engaged in pandemic influenza preparedness planning. Most resource-poor countries will be unable to stockpile antivirals or have access to eventual human vaccines for pandemic flu. Preparedness plans, directed at controlling avian influenza at the source, enable countries simultaneously to promote national and global health, animal welfare and international development. Improving the veterinary infrastructure and capacity of resource-poor countries is one way to prevent potential pandemic flu deaths in resource-rich countries. In this article, Amanda Martinot, James Thomas, Alejandro Thiermann and Nabarun Dasgupta argue that national health leaders need to consider more comprehensive strategies that incorporate veterinary surveillance and improvements in veterinary infrastructure for the control of avian influenza epizootics as part of national pandemic preparedness planning. This, they argue, will require a shift in attitude, from thinking in terms of preparation for an inevitable pandemic to pre emption of the potential pandemic through prevention measures in the animal population. PMID- 17351180 TI - Canine knee replacement and cruciate disease. PMID- 17351182 TI - BSE and the safety of milk. PMID- 17351183 TI - Concurrent tail docking and microchipping in puppies. PMID- 17351184 TI - Fowl typhoid in a small backyard laying flock. PMID- 17351185 TI - High-throughput determination of mode of inhibition in lead identification and optimization. AB - After finishing the primary high-throughput screening, the screening team is often faced with thousands of hits to be evaluated further. Effective filtering of these hits is crucial in identifying leads. Mode of inhibition (MOI) study is extremely useful in validating whether the observed compound activity is specific to the biological target. In this article, the authors describe a high-throughput MOI determination method for evaluating thousands of compounds using an existing screening infrastructure. Based on enzyme or receptor kinetics theory, the authors developed the method by measuring the ratio of IC(50) or percent inhibition at 2 carefully chosen substrate or ligand concentrations to define an inhibitor as competitive, uncompetitive, or noncompetitive. This not only facilitates binning of HTS hits according to their MOI but also greatly expands HTS utility in support of the medicinal chemistry team's lead optimization practice. Three case studies are presented to demonstrate how the method was applied successfully in 3 discovery programs targeting either an enzyme or a G protein-coupled receptor. PMID- 17351187 TI - The Coronary Artery Revascularization Prophylaxis (CARP) Trial: results and remaining controversies. AB - A high percentage of patients requiring elective vascular surgery also has indications for coronary artery revascularization, leading to varied opinions as to whether to undertake coronary artery revascularization first, to use risk stratification, or to do no coronary intervention before elective vascular surgery. The Coronary Artery Revascularization Prophylaxis (CARP) Trial determined the long-term benefit of coronary artery revascularization in patients with stable coronary artery disease undergoing elective infra-renal aortic or infra-inguinal vascular surgery. Following application of inclusion/exclusion criteria, those patients who did not require urgent vascular surgery or have significant co-existing conditions underwent cardiac evaluation and angiography. Eligible patients (stenosis >70% in one or more cardiac vessels) were randomized to either undergo coronary revascularization or to have no coronary intervention before vascular surgery; 5859 patients were screened and 4669 were excluded for clinical or other reasons. The remaining 1190 patients underwent coronary angiography following which 680 were excluded for clinical or other reasons. The remaining 510 were randomized to coronary artery revascularization (258) before vascular surgery and no coronary intervention before vascular surgery (252). Coronary artery revascularization neither improves long-term survival nor does it improve short-term outcomes for elective aortic or infra-inguinal vascular surgery. PMID- 17351188 TI - Commentary on "The Coronary Artery Revascularization Prophylaxis (CARP) Trial: results and remaining controversies". PMID- 17351189 TI - Aortic debranching procedures to facilitate endografting. AB - Since approval of the Gore TAG device in 2005, endo-grafting of isolated descending thoracic aneurysms has been a welcome replacement to open surgery by many vascular and cardiac surgeons. Obvious constraints of this new technology are seal zones relative to adjacent brachiocephalic and visceral vessels. This is particularly important with regard to the more extensive thoracoabdominal aortic aneurysms. Although branched or fenestrated stent grafts have been used for such cases, these technically advanced devices are not available for general use and, therefore, many practitioners are left with few alternatives other than standard open repair. Some centers have tinkered with various forms of extra-anatomic bypass to lengthen seal zone sites and facilitate stent graft repair. The lack of uniformity and long-term data hamper acceptance of this approach. This review attempts to cull all available information on this technique from recent case reports and series published in the literature. PMID- 17351190 TI - Commentary on "Aortic debranching procedures to facilitate endografting". PMID- 17351191 TI - Bioabsorbable stenting for peripheral arterial occlusive disease. AB - Bioabsorbable stents offer an unproven but theoretically appealing means to address the deficiencies of current stent designs. Ideally, these stents would provide early postprocedural scaffolding support yet undergo a predictable process of reabsorption, thus removing the persistent stimulus for neointimal hyperplasia. Prototypes include polymeric formulations and magnesium-based absorbable metal stents. Current and future human trials will ascertain if bioabsorbable stents truly deliver a physiologic advantage in the treatment of peripheral occlusive disease. PMID- 17351192 TI - Commentary on "Bioabsorbable stenting for peripheral arterial occlusive disease". PMID- 17351193 TI - Carotid stent trials: past, present, and future. AB - Carotid stenting has emerged as a therapeutic alternative to standard carotid endarterectomy in patients with carotid bifurcation disease. The percutaneous modality holds the potential to replace a large proportion of the carotid surgical procedures performed throughout the world. Carotid stenting has undergone technologic advances in the last decade, including improved sheaths and guides, lower profile balloons and stents, and the almost ubiquitous use of dependable distal embolization protection devices. Contemporary data confirm the safety and efficacy of the procedure for patients with high-grade lesions who are at higher-than-normal risk for standard open carotid repair. Whether lower-risk patients should be offered stenting as an alternative to carotid endarterectomy is a question that must await the results of ongoing clinical trials. PMID- 17351194 TI - Commentary on "Carotid stent trials--past, present, and future." Let's do it our way. PMID- 17351195 TI - Office-based treatment of venous disease. AB - Many recent developments in the care of venous disease have dramatically changed the options for office-based treatments. Traditionally relegated to patient education, compression, and wound care, office-based care is witnessing a dramatic change in treatment of patients particularly diagnosed with the full spectrum of chronic venous disease. These treatments primarily involve sclerotherapy, ambulatory phlebectomy, and percutaneous venous ablation. Although these procedures can be delivered in a general vascular surgery clinic, more effective and streamlined care may be best provided by forming a specialty vein clinic created specifically for patients with varicose veins or all stages of chronic venous disease. An overview about sclerotherapy, ambulatory phlebectomy, and percutaneous venous ablation treatments that can be safely performed in the office and the benefits of forming a clinic dedicated only to venous treatment are present. PMID- 17351196 TI - Commentary on "Office-based treatment of venous disease". PMID- 17351197 TI - Impact of plaque characterization on carotid interventions. AB - Plaque characterization is the first step in a process that will help guide physicians to select patients with atherosclerotic carotid disease that is at risk for subsequent neurologic sequelae. Multiple imaging modalities are undergoing investigation, with B-mode ultrasonography and magnetic resonance imaging showing the most promise for clinical applicability in the near future. These techniques provide excellent characterization of plaque components and appear to correlate with findings at the time of carotid interventions. Magnetic resonance findings may additionally predict transition of asymptomatic carotid plaques into symptomatic lesions. Computed tomography imaging as currently performed does not appear to evaluate plaque components adequately. Whether knowledge of plaque characteristics can be used to impact procedural outcomes remains speculative. PMID- 17351198 TI - Commentary on "Impact of plaque characterization on carotid interventions". PMID- 17351199 TI - Percutaneous interventions in dialysis access. AB - The creation and long-term management of dialysis accesses has been and remains a challenging aspect of vascular surgery practice. Until recently, vascular surgeons relied on open techniques to salvage and maintain dialysis fistulas and grafts. In the last 10 years, percutaneous approaches have become widely adopted and to this day continue to be refined as new devices and techniques are developed. Recent series have found similar technical success rates to open surgery, with the best results seen in the treatment of short-segment and anastomotic stenoses. Percutaneous interventions also allow for treatment of remote and surgically inaccessible lesions such as central vein stenoses. Some of the pitfalls of this approach include the exposure to thrombolytics, intravenous contrast, and radiation. Nevertheless, despite these limitations, a percutaneous approach has become first-line therapy in dialysis access management. PMID- 17351200 TI - Commentary on "Percutaneous interventions in dialysis access". PMID- 17351201 TI - Vagus nerve stimulation therapy for treatment of drug-resistant epilepsy and depression. AB - Vagal nerve stimulation therapy is a new adjunctive treatment for drug-resistant epilepsy and depression. It consists of a pulse generator that transmits impulses to the left vagus nerve via an implantable electrode and can be performed by surgeons familiar with the anatomy of the cervical vagus nerve. The minimum age for vagal nerve stimulation therapy for epilepsy is 12 years, and for depression, 18 years. Hoarseness and cough are the most common side effects. Response rates to vagal nerve stimulation therapy vary and depend on several other factors. If used as adjunctive therapy, vagal nerve stimulation has shown better control of seizures or depression at smaller doses of antiepileptic or antidepressive medications and also results in decreased dose-dependent side effects. Vagal nerve stimulation therapy appears safe as an adjunctive treatment for drug resistant epilepsy and depression. Long-term data are needed to better define its ultimate role in various subsets of patients. PMID- 17351202 TI - Commentary on "Vagus nerve stimulation therapy for treatment of drug-resistant epilepsy and depression". PMID- 17351203 TI - Advances in endovascular treatment of femoropopliteal arterial occlusive disease. AB - Over the past decade, accumulated experience and considerable advances in percutaneous endovascular techniques have enabled their use with increasing frequency for the management of peripheral arterial occlusive disease. However, despite the established role of endoluminal approaches in many other arterial territories, their application for the treatment of femoropopliteal occlusive disease is still debatable due to unique unfavorable anatomical, functional, and flow characteristics of this area. Conventional balloon angioplasty in the femoral and popliteal arteries is frequently associated with suboptimal results and high restenosis rates. To overcome these limitations, emerging approaches have been introduced or are currently under investigation. These include angioplasty modifications, newer concepts in stent design, adjunctive pharmacotherapy, debulking devices, and the application of gamma radiation and freezing in an attempt to reduce intimal hyperplastic response and consequently to expand the application of minimal invasive techniques in the hostile femoropopliteal environment. This review article will present the current status and future trends of endovascular therapy of femoropopliteal artery occlusive disease. PMID- 17351207 TI - Bradycardia in minor trauma: don't be slow on the uptake! AB - We report the case of a 13-year-old boy presenting with profound bradycardia following minor trauma. Our patient had gastroschisis at birth and has moderate learning difficulties but is otherwise fit and well. Whilst playing at home he fell sustaining a minor cervical hyperextension injury. He immediately complained of tetraplegia and hyposensibility. The ambulance crew noted profound bradycardia with normotension and he was transported to hospital with full spinal immobilisation precautions. Over the subsequent 2 hours he made a full neurological recovery. Bradycardia persisted with a beat-to-beat variation of 30 60 bpm. ECG showed sinus bradycardia with atrial ectopics and he remained haemodynamically normal. Neuroimaging studies revealed hypoplasia of the odontoid peg with a relative narrowing of the spinal canal at this level. There was no evidence of spinal cord contusion or compression. His bradycardia resolved over 36 hours without further intervention. On discharge the patient was advised to wear a cervical hard collar when mobilising. This association of a craniocervical abnormality with learning difficulties, and gastroschisis has not been previously described. We discuss several other causes of odontoid peg instability, which may lead to severe autonomic effects with relatively insignificant trauma. PMID- 17351208 TI - Fulminant Wegener's granulomatosis presenting as epistaxis. AB - The case of a 63-year-old woman who presented to the emergency department with epistaxis and haemodynamic instability is reported. Subsequent investigation showed renal failure and multiple pulmonary nodules. A positive proteinase 3 antineutrophil cytoplasmic antibody test supported the diagnosis of fulminant Wegener's granulomatosis, requiring urgent dialysis, plasma exchange and immunosuppression. This is the first report in the emergency literature of Wegener's granulomatosis presenting as acute epistaxis. Emergency physicians should consider Wegener's granulomatosis in patients with atypical epistaxis. In patients presenting with clinically severe, active disease early proteinase 3 antineutrophil cytoplasmic antibody testing is recommended. PMID- 17351209 TI - Lodged oesophageal button battery masquerading as a coin: an unusual cause of bilateral vocal cord paralysis. AB - An 11-month-old girl with an oesophageal foreign body was presented: from the radiographic appearance it was presumed to be a coin. Microlaryngoscopy 5 h after ingestion revealed a button battery impacted in the hypopharynx with severe damage to the oesophageal mucosa. The patient was intubated for 6 days in the intensive care unit because of stridor and respiratory distress. Repeat microlaryngoscopy demonstrated bilateral vocal cord palsy, which was presumed to be secondary to the involvement of the recurrent laryngeal nerves in the injury. We recommend that in the absence of a history of observed ingestion, it should be assumed that coin-like foreign bodies are button batteries until proven otherwise. PMID- 17351210 TI - Spontaneous cervical cord haemorrhage: an unusual presentation. AB - Spontaneous haemorrhage within or compressing the spinal cord is a rare condition that requires emergency investigation and treatment. Such a case presenting with rapidly progressive flaccid quadriparesis, with subsequent ventilatory failure is reported. In this case the patient probably had an unfortunate complication of hypertension and over-anticoagulation. PMID- 17351211 TI - Haemothorax after pig-tail catheter removal in a patient with primary spontaneous pneumothorax. AB - A case of haemothorax is described which occurred after the removal of a small pig-tail chest tube (8.5 F) that was inserted in the second intercostal space in the mid-clavicular line, for primary spontaneous pneumothorax management. The patient was successfully resuscitated and 0.85 l of blood was aspirated. There was no evidence for pre-existing haemothorax, no metal instrument was used and no precipitating factor was present. Thus, it is possible that bleeding was due to a tear of a vessel proximal to the second intercostal space during pig-tail catheter removal by a "grapple-hook" mechanism. Whether a pig-tail catheter in itself carries an additional risk of complications compared with other catheter types is questionable. However, this report highlights the potential danger that accompanies pig-tail drain insertion into the second intercostal space in the mid clavicular line, and suggests that insertion in other sites is technically easy and potentially safer for pneumothorax drainage. PMID- 17351212 TI - Beware of prosthetic valve thrombosis despite therapeutic anticoagulation. AB - Patients with mechanical heart valves require anticoagulation within carefully controlled ranges to prevent valve thrombosis, a life-threatening condition. The majority of doctors will be required to manage anticoagulation, often on a temporary basis such as during elective procedures. As long-term anticoagulation management moves away from specialised hospital clinics, there needs to be widespread awareness of the complications of sub-therapeutic international normalised ratios (INRs). PMID- 17351213 TI - Allergy evaluation after emergency treatment: anaphylaxis to the over-the-counter medication clobutinol. AB - Anaphylaxis is traditionally diagnosed and treated as an acute emergency but should be always followed by a search for specific triggers, resulting in avoidance strategies. This case report highlights the relevance of a detailed evaluation after anaphylaxis for diagnosis of a rare but potentially life threatening allergy. Considering the high frequency of clobutinol application, IgE-mediated allergic hypersensitivity seems extremely rare and has to be distinguished from infection-associated urticaria and angioedema as well as non specific summation effects. Accidental re-exposure has to be strictly avoided and therefore after identification of clobutinol as the anaphylaxis trigger, the patient received detailed allergy documents including international non proprietary and trade names of the culprit drug. PMID- 17351214 TI - For whom the bell tolls. PMID- 17351215 TI - Should exercise treadmill testing be provided in the emergency department? PMID- 17351216 TI - Clarification of cyanide's effect on oxygen transport characteristics in a canine model. AB - OBJECTIVE: To clarify the cardiovascular mechanisms of cyanide poisoning by evaluating oxygen transport characteristics using a canine model. METHODS: A prospective controlled experiment was performed at a hospital-based animal laboratory. Five male beagle (17 (2) kg) dogs were anesthetised with alpha chloralose, paralysed with pancuronium bromide and mechanically ventilated. Potassium cyanide was infused at 0.045 mg/kg/min for 110 min. Heart rate, blood pressure, cardiac output, oxygen delivery (DO2), oxygen consumption (VO2) and oxygen extraction ratio (OER) were measured every 10 min for 140 min. DO2 was measured by an indirect calorimeter. RESULTS: Cyanide and lactate levels peaked at 1.52 (0.25) mg/l and 9.1 (1.5) mmol/l, respectively. Systolic blood pressure remained relatively constant whereas diastolic blood pressure decreased by 19%. Cardiac output, heart rate and DO2 increased to a maximum of 6%, 10% and 10%, respectively, at 40 min, after which they declined to a low of 32%, 28% and 30% below baseline, respectively. Stroke volume remained constant. Oxygen consumption initially increased by 5%, then decreased to 24% below baseline. The OER initially declined to 35% below baseline, then increased throughout the rest of the study. CONCLUSION: Cyanide poisoning in the canine model showed two phases of injury. The first (compensated) phase had a mechanism consistent with a traditional global oxygen consumption defect. The second (decompensated) phase had a mechanism consistent with heart failure. This heart failure was due to bradycardia. These data suggest chronotropy as an avenue of further study in the temporary treatment of cyanide poisoning. PMID- 17351217 TI - Bayes pulmonary embolism assisted diagnosis: a new expert system for clinical use. AB - BACKGROUND: The diagnosis of pulmonary embolism demands flexible decision models, both for the presence of clinical confounders and for the variability of local diagnostic resources. As Bayesian networks fully meet this requirement, Bayes Pulmonary embolism Assisted Diagnosis (BayPAD), a probabilistic expert systems focused on pulmonary embolism, was developed. METHODS: To quantitatively validate and improve BayPAD, the system was applied to 750 patients from a prospective study done in an Italian tertiary hospital where the true pulmonary embolism status was confirmed using pulmonary angiography or ruled out with a lung scan. The proportion of correct diagnoses made by BayPAD (accuracy) and the correctness of the pulmonary embolism probabilities predicted by the model (calibration) were calculated. The calibration was evaluated according to the Cox regression calibration model. RESULTS: Before refining the model, accuracy was 88.6%. Once refined, accuracy was 97.2% and 98%, respectively, in the training and validation samples. According to Cox analysis, calibration was satisfactory, despite a tendency to exaggerate the effect of the findings on the probability of pulmonary embolism. The lack of some investigations (like Spiral computed tomographic scan and Lower limbs doppler ultrasounds) in the pool of available data often prevents BayPAD from reaching the diagnosis without invasive procedures. CONCLUSIONS: BayPAD offers clinicians a flexible and accurate strategy to diagnose pulmonary embolism. Simple to use, the system performs case-based reasoning to optimise the use of resources available within a particular hospital. Bayesian networks are expected to have a prominent role in the clinical management of complex diagnostic problems in the near future. PMID- 17351218 TI - Endotracheal tube and laryngeal mask airway cuff volume changes with altitude: a rule of thumb for aeromedical transport. AB - BACKGROUND: Helicopters and light (unpressurised) aircraft are used increasingly for the transport of ventilated patients. Most of these patients are ventilated through endotracheal tubes (ETTs), others through laryngeal mask airways (LMAs). The cuffs of both ETTs and LMAs inflate with increases in altitude as barometric pressure decreases (30 mbar/1000 feet). Tracheal mucosa perfusion becomes compromised at a pressure of approximately 30 cm H2O; critical perfusion pressure is 50 cm H2O. METHODS: The change in dimensions of the inflated cuffs of a size 8 ETT and a size 5 LMA were measured with digital callipers at 1000 feet intervals in the unpressurised cabin of an Agusta 109 helicopter used by the Warwickshire and Northamptonshire Air Ambulance. RESULTS: A linear expansion in cuff dimensions as a function of altitude increase was identified. For ETTs, a formula for removal of air from the cuff with increasing altitude was calculated and is recommended for use in aeromedical transfers. This is 1/17x1.1 = 0.06 ml/1000 foot ascent/ml initial cuff inflation. CONCLUSION: The data for LMA cuff expansion failed to show significant correlation with altitude change. Further work is required to determine a similar rule of thumb for LMA cuff deflation. PMID- 17351219 TI - Stability of succinylcholine solutions stored at room temperature studied by nuclear magnetic resonance spectroscopy. AB - The effect of storage temperature on the stability of two succinylcholine chloride solutions (20 and 50 mg/ml) was evaluated. Molecular composition was analysed using nuclear magnetic resonance spectroscopy. At room temperature, the degradation rate constant was 1.2%/month for the 20 mg/ml solution and 2.1%/month for the 50 mg/ml solution. The corresponding monthly degradation rates for the two solutions were 0.18% and 0.30% when stored at 4 degrees C, and 5.4% and 8.1% when stored at 37 degrees C. If a 10% loss of potency is considered acceptable, then the 20 and 50 mg/ml succinylcholine solutions can be stored in emergency resuscitation carts at room temperature for 8.3 and 4.8 months, respectively. PMID- 17351220 TI - Validation of the Emergency Severity Index (ESI) in self-referred patients in a European emergency department. AB - OBJECTIVE: To validate the Emergency Severity Index (ESI) triage algorithm in predicting resource consumption and disposition by self-referred patients in a European emergency department. METHODS: This was a prospective, observational cohort study using a convenience sample of self-referred emergency department patients >14 years of age presenting to a busy urban teaching hospital during a 39-day period (27 May-4 July 2001). Observed resource use was compared with resource utilisation predicted by the ESI. Outpatient referrals after discharge and hospitalisations were also recorded. RESULTS: ESI levels were obtained in 1832/3703 (50%) self-referred patients, most of whom were in the less severe ESI 4 (n = 685, 37%) and ESI-5 (n = 983, 54%) categories. Use of resources was strongly associated with the triage level, rising from 15% in ESI-5 to 97% in ESI 2 patients. Specialty consultations and admissions also rose with increasing ESI severity. Only 5% of ESI-5 patients required consultation and <1% were admitted, whereas 85% of ESI-2 patients received a consultation and 56% were admitted, 26% to a critical care bed. Only 2% of the ESI-5 patients underwent blood tests, compared with 76% of the sicker ESI-2 patients. X rays were the most commonly used resource in patients triaged to ESI-4 and ESI-5. CONCLUSION: The ESI triage category reliably predicts the severity of a patient's condition, as reflected by resource utilisation, consultations and admissions in a population of self referred patients in a European emergency department. It clearly identifies patients who require minimal resources, or at most an x ray, and those unlikely to require admission. PMID- 17351221 TI - A population follow-up study of patients who left an emergency department without being seen by a medical officer. AB - OBJECTIVES: To describe the population of emergency department patients who leave without being seen by a medical officer, to investigate the circumstances of their visit and to ascertain whether they subsequently receive alternative medical care. METHODS: A follow-up study was conducted of patients who were initially triaged, but left without being seen by a medical officer between July 2003 and October 2003 in a tertiary referral hospital emergency department in Sydney, Australia. Emergency Department Information System data were reviewed for population demographics, presenting complaints and acuity rating of patients. Follow-up telephone interviews were conducted within 7 days after the patient left the emergency department. RESULTS: During the study period, 8.6% (1272 of 14 741) of the emergency department patients left without seeing a doctor and 35.9% (457 of 1272) of these patients who walks out were contacted for follow-up. The results from bivariate and multivariate analyses showed that walkout rates significantly varied by sociodemographic and clinical characteristics of the patients. Young patients aged 0-29 years, and those with longer waiting time for triage and triaged as "less urgent" were more likely to walk out than others. Overcrowding in the emergency department had a significant association with walkout of patients. Prolonged waiting time was the most common reason for leaving emergency departments without being seen by a doctor. Only 12.7% (58 of 457) of the walkout patients revisited emergency departments within 7 days of their departure and of those who were subsequently admitted following their return to hospital accounted for 5.0% (23 of 457). Of the follow-up patients, 39.4% felt angry about their emergency department experiences. CONCLUSIONS: The number of patients who leave an emergency department without seeing a doctor is strongly correlated with waiting time for medical review. Achieving shorter emergency department waiting times is central to reducing the numbers of people leaving without being seen. The rate of patients who leave without being seen is also strongly correlated with triage category. These findings highlight the importance of accurate triaging, as this clearly influences waiting time. It is also likely that there are patients who benefit from the reassurance of the triage assessment, and therefore feel less urgency for medical review. These may be cases where immediate medical review is not essential. This area should be further explored. These results are important for planning and staffing health services. Decision makers should identify and target factors to minimise walkouts from public hospital emergency departments. PMID- 17351222 TI - The East Anglian specialist registrar assessment tool. AB - BACKGROUND: In our region, it was acknowledged that the process of assessment needed to be improved, but before developing a system for this, there was a need to define the "competent or satisfactory trainee". OBJECTIVE: To outline the process by which a consensus was achieved on this standard, and how a system for formally assessing competency across a wide range of knowledge skills and attitudes was subsequently agreed on, thus enabling increased opportunities for training and feedback and improving the accuracy of assessment in the region. METHODS: The opinions of trainees and trainers from across the region were collated, and a consensus was achieved with regard to the minimum acceptable standard for a trainee in emergency medicine, thus defining a competent trainee. The group that set the standard then focused on identifying the assessment methods most appropriate for the evaluation of the knowledge, skills and attitudes required of an emergency medicine trainee. The tool was subsequently trialled for a period of 6 months, and opinion evaluated by use of a questionnaire. RESULTS: The use of the tool was reviewed from both the trainers' and trainees' perspectives. 42% (n = 11) of trainers and 31% (n = 8) trainees responded to the questionnaire. In the region, there were 26 trainers and 26 trainees. Five trainees and nine trainers had used the tool. 93% (14/15) of respondents thought that the descriptors used to describe the satisfactory trainee were acceptable; 89% (8/9) of trainers thought that it helped them assess trainees more accurately. 60% (3/5) of trainees thought that, as a result, they had a better understanding of their weak areas. CONCLUSION: We believe that we achieved a consensus across our region as to what defined a satisfactory trainee and set the standard against which all our trainees would subsequently be evaluated. The use of this tool to assess trainees during the pilot period was disappointing; however, we were encouraged that most of those using the tool thought that it allowed an objective assessment of trainees and feedback on areas requiring further work. Those who used the tool identified important reasons that may have hindered widespread use of the assessment tool. PMID- 17351223 TI - Do emergency department physiotherapy practitioner's, emergency nurse practitioners and doctors investigate, treat and refer patients with closed musculoskeletal injuries differently? AB - INTRODUCTION: This paper aims to assess whether emergency department physiotherapy practitioner's (EDPPs), emergency nurse practitioner's (ENPs) and emergency department doctors investigate, treat and refer patients with closed musculoskeletal injuries differently. METHOD: The emergency department records of patients who fitted the departmental criteria for being treated by either ENPs, EDPPs or doctors were selected retrospectively during a 2 1/2 month period between 1 March and 15 May 2005. The investigation, management and referral or discharge of these patients were analysed. RESULTS: There was no significant difference between the proportion of patients sent for x ray and the type of clinician. (p = 0.17) There was also no significant difference between the proportions of x rays found to have fractures/dislocations with each type of clinician (p = 0.99). All fractures and dislocations were found to have been managed following the written departmental protocols. Consequently, further analysis was for soft tissue injuries only. For soft tissue injuries, senior house officers gave more patients analgesia/non-steroidal anti-inflammatory drugs compared with other clinicians (86%, p<0.001). ENPs gave more structural support (bandages, etc) compared with other clinicians (80%, p<0.001). Consultant's arranged the least formal follow-up although this was not significant (7.6%, p = 0.054) and middle grades offered the most follow-up (17%, p = 0.054) with this again not being significant. However, EDPPs referred significantly more patients for physiotherapy follow-up (9.2%, p = 0.031). CONCLUSION: ENPs, EDPPs and doctors of all grades investigated patients with fractures and dislocations similarly and managed them following the written departmental guidelines. However, there were statistically significant differences in the way patients with closed soft tissue injuries were treated and followed-up. PMID- 17351224 TI - Bupivacaine in the emergency department is underused: scope for improved patient care. AB - AIMS: To determine patterns of local anaesthetic use, knowledge and perceived use of local anaesthetic by emergency department doctors, and barriers to bupivacaine use. METHODS: This was a multifaceted, observational study undertaken at two large metropolitan emergency departments. It comprised a retrospective chart review of patients who had been given local anaesthetic in the emergency department, an examination of ordering records of local anaesthetics in the emergency department, and a cross-sectional survey of emergency department doctors. RESULTS: The charts of 95 patients were reviewed. Most (93.7%) injuries were lacerations and the most common site was the hand (41.4%). 88 (92.6%), 4 (4.2%) and 3 (3.2%) patients were given lignocaine, prilocaine (Bier's blocks) and bupivacaine (digital blocks), respectively. Four (4.2%) cases were identified for which bupivacaine was likely to have been a better alternative than the lignocaine used. These were finger/hand injuries likely to be associated with considerable prolonged pain. The emergency department pharmacy records indicated that 30 times more lignocaine than bupivacaine was ordered in 2004-5. 30 (88.2%) of 34 doctors completed the survey. Knowledge of local anaesthetic pharmacology was variable: 33% and 66% did not know that bupivacaine was more cardiotoxic and that lignocaine was more painful, respectively. The main barriers to bupivacaine use were "habit" of using lignocaine (46.7%), cardiac toxicity (40%) and slower onset (30%). CONCLUSION: Bupivacaine seems to be underused in some appropriate circumstances. Accordingly, there is scope for improvement in patient care through critical evaluation of local anaesthetic practice. This is particularly necessary because barriers to bupivacaine use are often non-clinical (habit, availability, familiarity) rather than clinical (toxicity, onset time). PMID- 17351225 TI - The College of Emergency Medicine curriculum: is the specialty-specific knowledge section fit for purpose? AB - OBJECTIVE: To determine whether the knowledge specified in the specialty-specific section of the College of Emergency Medicine curriculum covered the diagnoses presenting to a UK teaching hospital emergency department. METHOD: An audit of 1000 sets of notes was undertaken, the diagnosis abstracted and mapped to the curriculum. RESULTS: 1076 diagnoses were derived and all were covered by the curriculum. The three most common diagnostic categories were musculoskeletal, wound management and cardiology. CONCLUSION: The curriculum covered all the diagnoses in this sample. Knowing the frequency of a diagnosis could be used to inform training and assessment. PMID- 17351226 TI - The intubating laryngeal mask: is there a role for paramedics? AB - OBJECTIVE: To compare the ability of UK paramedics to intubate a simulated difficult airway using a Mackintosh laryngoscope versus an intubating laryngeal mask airway (ILMA). METHOD/DESIGN: A randomised controlled trial. RESULTS: 100% of the paramedics were able to intubate a simulated difficult airway using the ILMA versus 0% of those using the Mackintosh laryngoscope. CONCLUSIONS: This study has demonstrated the ability of paramedics to use the ILMA when faced with a difficult intubation. However, further evaluation of this potential role for the ILMA is required. PMID- 17351227 TI - Safe access/egress systems for emergency ambulances. AB - OBJECTIVE: To comparatively evaluate the three most widely used ambulance stretcher loading systems; easi-loader, ramp/winch and tail lift to identify a preferred system based on safety and usability evidence. METHODS: Three data types were collected in the field, the laboratory and from a national questionnaire. Field data were collected using the qualitative methods of observation (link analysis and hierarchical task analysis) and interview (critical incident technique) over 12 months during 2004-5. Laboratory data were collected for detailed postural analysis. A national ranking questionnaire was used to prioritise the resulting design issues. RESULTS: The field study data were analysed, triangulated and summarised in a taxonomy to identify the design and operational issues. A list of 14 criteria was used in a national ranking exercise with 134 ambulance staff and manufacturers. Patient and operator safety was ranked as the highest priority, followed by manual handling. The postural analysis found that the easi-loader system presented the highest postural risk. CONCLUSIONS: The tail lift was found to be the preferred and safest loading system from both the field and laboratory research and is the recommended option from the evaluated loading systems. PMID- 17351228 TI - Hypokalaemia and sudden cardiac death--lessons from implantable cardioverter defibrillators. AB - The cases of four patients experiencing ventricular arrhythmia secondary to drug induced hypokalaemia requiring treatment by a previously implanted cardioverter defibrillator (ICD) are reported here. In three cases, hypokalaemia developed within a short period of time after modification of diuretic regimen with loop and thiazide diuretics had been carried out or potassium-sparing drugs had been withdrawn. In one patient, hypokalaemia occurred after months of treatment with several potassium-sparing and non-potassium-sparing diuretics. The fact that the combination of thiazide and loop diuretics can be associated with pronounced hypokalaemia and life-threatening arrhythmias, which may be terminated by device treatment in patients with an ICD but may be fatal in patients with structural heart disease but without an ICD, is highlighted here. Prompt recognition and correction of hypokalaemia is mandatory if such patients present to the emergency department. PMID- 17351229 TI - Low-flow priapism needs recognition and early correct treatment. AB - Low-flow priapism is a rare condition whereby there is a persistent, painful erection. The patient often presents late because of embarrassment. Failure to recognise this as an emergency and instigate immediate treatment may lead to cavernosal tissue ischaemia, fibrosis and subsequent long-term impotence. A case of low-flow priapism, that demonstrated a lack of urgency and understanding is discussed. An internet-based literature search provided a treatment regimen with resolution of tumescence. PMID- 17351230 TI - Do peripheral blood cultures taken in the emergency department influence clinical management? AB - BACKGROUND: Blood cultures are routinely used to investigate suspected sepsis in the emergency department despite several studies showing their limited influence on patient management. OBJECTIVES: To quantify the use and clinical relevance of blood cultures obtained in the emergency department. METHODS: A retrospective study of blood cultures taken in the emergency department between 1 January 2003 and 31 December 2004. Microbiology results and patients' records were reviewed to determine the influence of positive cultures on subsequent patient management. RESULTS: 2213 blood cultures were taken in the emergency department over the study period. 132 (6%) yielded a positive result. Three positive cultures had incomplete information. Of the remaining 129 positive cultures, 30 (1.4% of all cultures) were "true positives" and 4 (0.18%) influenced subsequent patient management. CONCLUSIONS: Blood cultures taken in our emergency department (Southern General Hospital, Glasgow, UK) rarely yield bacterial growth, and over 2 years only four cultures seemed to directly influence patient management. Better guidelines are required for targeted use of blood cultures in the emergency department. PMID- 17351231 TI - Do peripheral blood cultures taken in the emergency department influence clinical management? AB - BACKGROUND: Blood cultures are routinely used to investigate suspected sepsis in the emergency department despite several studies demonstrating their limited influence on patient management. OBJECTIVES: To quantify the use and clinical relevance of blood cultures obtained in the emergency department. METHODS: A retrospective study of blood cultures taken in the emergency department between 1 January 2003 and 31 December 2004. Microbiology results and patient records were reviewed to determine the influence of positive cultures on subsequent patient management. RESULTS: 2213 blood cultures were taken in the emergency department over the study period. 132 (6%) yielded a positive result. Three positive cultures cases had incomplete information. Of the remaining 129 positive cultures, 30 (1.4% of all cultures) were "true positives" and 4 (0.18%) influenced subsequent patient management. CONCLUSIONS: Blood cultures taken in our emergency department rarely yield bacterial growth and over 2 years, only four seemed to directly influence patient management. Better guidelines are required for targeted use of blood cultures in the emergency department. PMID- 17351232 TI - Life-threatening episode after ingestion of toad eggs: a case report with literature review. AB - It is known that toad possesses several toxic substances in the skin and parotid glands. In the past, toad-venom poisoning had been reported from ingestion of toad soup, Kyushin and aphrodisiac pills, but the poisoning from toad eggs is observed for the first time. The case of a healthy female who had previously eaten toad soup twice without any discomfort is reported. She developed gastrointestinal symptoms and life-threatening cardiac rhythm after ingestion of toad eggs. PMID- 17351233 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Conservative management or suturing for small, uncomplicated hand wounds. AB - A short cut review was carried out to establish whether suturing provided any advantage over conservative management for small, uncomplicated hand wounds. Only one paper presented a trial addressing the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this paper are tabulated. The clinical bottom line is that there doesn't appear to be any great advantage to suturing. The importance of clinical evaluation, to ensure that the wound really is uncomplicated, is stressed. PMID- 17351235 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. C Reactive Protein and the diagnosis of intracranial infection. AB - A short cut review was carried out to determine whether measuring C Reactive Protein might help in the diagnosis of intracranial infection in a patient presenting to the Emergency department with an acute headache. 62 papers were found, but none answered the question. The clinical bottom line is that there doesn't appear to be any evidence for, or against, the use of C Reactive Protein in the diagnosis of intracranial infection in patients presenting to the Emergency department with an acute headache. PMID- 17351236 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Prophylactic antibiotics are not indicated in uncomplicated hand lacerations. AB - A short cut review was carried out to establish whether prophylactic antibiotics should be used as part of the management of uncomplicated hand lacerations. From a search of 237 papers only five presented trials addressing the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this paper are tabulated. The clinical bottom line is that there doesn't appear to be any evidence to support the use of prophylactic antibiotics in uncomplicated hand lacerations. PMID- 17351237 TI - The prehospital management of chest injuries: a consensus statement. Faculty of Pre-hospital Care, Royal College of Surgeons of Edinburgh. AB - This paper provides a guideline for the management of prehospital chest injuries after a consensus meeting held by the Faculty of Prehospital Care, Royal College of Surgeons of Edinburgh, Edinburgh, UK, in January 2005. An overview of the prehospital assessment, diagnosis and interventions for life threatening chest injury are discussed, with the application of skills depending on the training, experience and competence of the individual practitioner. PMID- 17351238 TI - A dramatic drop in blood pressure following prehospital GTN administration. AB - A male in his sixties with no history of cardiac chest pain awoke with chest pain following an afternoon sleep. The patient did not self medicate. The patient's observations were within normal limits, he was administered oxygen via a face mask and glyceryl trinitrate (GTN). Several minutes after the GTN the patient experienced a sudden drop in blood pressure and heart rate, this was rectified by atropine sulphate and a fluid challenge. There was no further deterioration in the patient's condition during transport to hospital. There are very few documented case like this in the prehospital scientific literature. The cause appears to be the Bezold-Jarish reflex, stimulation of the ventricular walls which in turn decreases sympathetic outflow from the vasomotor centre. Prehospital care providers who are managing any patient with a syncopal episode that fails to recover within a reasonable time frame should consider the Bezold Jarisch reflex as the cause and manage the patient accordingly. PMID- 17351240 TI - Case of the month: Honey I glued the kids: tissue adhesives are not the same as "superglue". AB - A case of a father who treated his child's facial laceration with the home supply of "superglue" having been previously misinformed that superglue is used to treat lacerations is presented. The differences between tissue adhesive and superglue are described and suggest that emergency staff should be careful to avoid using the term "superglue" when using tissue adhesives. PMID- 17351241 TI - An unusual presentation of foreign-body ingestion at the emergency department. PMID- 17351242 TI - Calcaneal avulsion fracture. PMID- 17351243 TI - Complications of yoga. PMID- 17351244 TI - A guide to reducing citation errors in bibliographies. PMID- 17351245 TI - Photokeratitis following the manipulation of aquaria disinfection lamps. PMID- 17351246 TI - Attitudes to triage of Chinese emergency room patients in a Beijing tertiary hospital. PMID- 17351247 TI - Medico-legal consideration of gastric lavage in acutely intoxicated patients. PMID- 17351248 TI - Comparing nitrate storage and remobilization in two rice cultivars that differ in their nitrogen use efficiency. AB - Soil nitrogen (N) is available to rice crops as either nitrate or ammonium, but only nitrate can be accrued in cells and so factors that influence its storage and remobilization are important for N use efficiency (NUE). The hypothesis that the ability of rice crops to remobilize N storage pools is an indicator of NUE was tested. When two commonly grown Chinese rice cultivars, Nong Ken (NK) and Yang Dao (YD), were compared in soil and hydroponics, YD had significantly greater NUE for biomass production. The ability of each cultivar to remobilize nitrate storage pools 24 h after N supply withdrawal was compared. Although microelectrode measurements of the epidermal sub-cellular nitrate pools in leaves and roots showed similar patterns of vacuolar remobilization in both cultivars, whole-tissue analysis showed very little depletion of storage pools after 24 h. However, leaf epidermal cell cytosolic nitrate activities were significantly higher in YD when compared with NK. Before N starvation and growing in 10 mM nitrate, the xylem nitrate activity in YD was lower than that of NK. After 24 h of N starvation the xylem nitrate had decreased more in YD than in NK. Tissue analysis of stems showed that YD had accumulated significantly more nitrate than NK, and the remobilization pattern suggested that this store is important for both cultivars. Changes in nitrate reductase activity (NRA) and expression were measured. Growing in 10 mM nitrate, NRA was undetectable in roots of both cultivars, and the leaf total NRA of equivalent leaves was similar in NK and YD. When the N supply was withdrawn, after 24 h NRA in NK was reduced to 80% but no decrease was found in YD. The proportion of NRA in an active form in YD was significantly higher than that in NK under both nitrate supply and deprivation conditions. Checking NR gene expression showed that leaf expression of OsNia1 was faster to respond to nitrate deprivation than OsNia2 in both cultivars. These measurements are discussed in relation to cultivar differences and physiological markers for NUE in rice. PMID- 17351249 TI - Biology of the molybdenum cofactor. AB - The transition element molybdenum (Mo) is an essential micronutrient for plants where it is needed as a catalytically active metal during enzyme catalysis. Four plant enzymes depend on molybdenum: nitrate reductase, sulphite oxidase, xanthine dehydrogenase, and aldehyde oxidase. However, in order to gain biological activity and fulfil its function in enzymes, molybdenum has to be complexed by a pterin compound thus forming the molybdenum cofactor. In this article, the path of molybdenum from its uptake into the cell, via formation of the molybdenum cofactor and its storage, to the final modification of the molybdenum cofactor and its insertion into apo-metalloenzymes will be reviewed. PMID- 17351250 TI - Pressure gradients along whole culms and leaf sheaths, and other aspects of humidity-induced gas transport in Phragmites australis. AB - Emergent aquatic macrophytes growing in waterlogged anaerobic sediments overlain by deep water require particularly efficient ventilating systems. In Phragmites australis (Cav.) Trin. ex Steud, pressurized gas flows, generated by humidity induced diffusion of air into leaf sheaths, enhance oxygen transport to below ground parts and aid in the removal of respiratory CO2 and sediment-generated CO2 and methane. Although modelling and flow measurements have pointed to the probable involvement of all leaf sheaths in the flow process and the development of pressure gradients along the whole lengths of living culm and leaf sheaths, direct measurements of pressure gradients have never been reported. The aim of this study was to search for pressure gradient development in Phragmites culms and leaf sheaths and to determine their magnitudes and distribution. In addition, dynamic (with gas flow) and static pressures (no flow condition) and their relationship to flows, leaf sheath areas, and living-to-dead culm ratios were further investigated. Dynamic pressures (DeltaPd) recorded in the pith cavities of intact (non-excised) leafy culms, pneumatically isolated from the below-ground parts and venting through an artificial bore-hole near the base, revealed a curvilinear gradient of pressure 'asymptoting' towards the tips of the culms. Similarly, DeltaPd in upper and lower parts of leaf sheaths increased with distance from the base of the culm, with values in the upper parts always being greater. Curvilinear gradients of pressure were also found along pneumatically isolated individual leaf sheaths, but radial channels linking the leaf sheath aerenchyma with the pith cavity of the culm appeared to offer little resistance to flow. In keeping with predictions, static pressure differentials (DeltaPs) achieved in intact and excised culms and single leaf sheaths on intact culms proved to be relatively independent of leaf sheath area, whereas the potential for developing convective flows (pressure-driven flows) increased with increasing leaf sheath area. As measured by the ventilating coefficient [1 (DeltaPd/(DeltaPs)] the old dead (efflux) to living (influx) culm ratio of 1:12 compared with 1:25 raised ventilating efficiency from 31% to 71%, giving flows per tall culm into the rhizome system of c. 2.8 cm3 and 6.5 cm3 min-1, respectively. It was concluded that dynamic pressure gradients probably extend along the whole length of the leafy culms and leaf sheaths of Phragmites and that all leaf sheaths and all exposed points along the leaf sheaths can contribute convective gas-flow to the rhizome system. PMID- 17351251 TI - Reduced host cell reactivation of oxidative DNA damage in human cells deficient in the mismatch repair gene hMSH2. AB - Germ line mutations in the mismatch repair (MMR) genes hMSH2 and hMLH1 account for approximately 98% of hereditary non-polyposis colorectal cancers. In addition, there is increasing evidence for an involvement of MMR gene expression in the response of cells to UV-induced skin cancer. The link between MMR and skin cancer suggests an involvement of MMR gene expression in the response of skin cells to UV-induced DNA damage. In this report, we have used two reporter gene assays to examine the role of hMSH2 and hMLH1 in the repair of oxidative DNA damage induced by UVA light and DNA damage caused by methylene blue plus visible light (MB+VL). UVA and MB+VL produce 8-hydroxyguanines in DNA that are repaired by base excision repair (BER). AdHCMVlacZ is a replication-deficient recombinant adenovirus that expresses the beta-galactosidase (beta-gal) reporter gene under the control of the human cytomegalovirus (CMV) immediate-early promoter. We show a reduced host cell reactivation for beta-gal expression of UVA-treated and MB+VL treated AdHCMVlacZ in hMSH2-deficient LoVo human colon adenocarcinoma cells compared to their hMSH2-proficient counterpart SW480 cells, but not in hMLH1 deficient HCT116 human colon adenocarcinoma cells compared to hMLH1-proficient HCT116-chr3 cells. We have also reported previously that enhanced expression of the undamaged AdHCMVlacZ reporter gene is induced by the pre-treatment of cells with lower levels of the DNA-damaging agent and to higher expression levels in transcription-coupled repair (TCR)-deficient compared to TCR-proficient cells. Here we show that pre-treatment of cells with UVA or MB+VL enhanced expression of the undamaged reporter gene to a higher level in LoVo compared to SW480 cells but there was little or no difference in HCT116 compared to HCT116-chr3 cells. These results suggest a substantial involvement of hMSH2 but little or no involvement of hMLH1 in the repair of UVA- and MB+VL-induced oxidative DNA damage by BER. PMID- 17351252 TI - Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP). AB - BACKGROUND: High cure rates are expected in good-risk metastatic nonseminomatous germ-cell tumor (NSGCT) patients with bleomycin, etoposide and cisplatin. PATIENTS AND METHODS: Patients received either three cycles of BE500P or four cycles of E500P every 3 weeks. Disease was defined according to the Institut Gustave Roussy prognostic model. Patients were retrospectively assigned into the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. A sample size of 250 patients was necessary for an expected favorable response rate (primary end point) of 90% and not more than a 10% difference between the two arms. RESULTS: Among 257 assessable patients, 124 and 122 patients achieved a favorable response in the 3BE500P and 4E500P arms, respectively (P = 0.34). Median follow-up was 53 months. The 4-year event-free survival rates were 91% and 86%, respectively (P = 0.135). The 4-year overall survival rates were not significantly different [five deaths versus 12 deaths, respectively (P = 0.096)]. Similar nonsignificant trends were observed in good IGCCCG prognosis patients. CONCLUSIONS: Both regimens produced similar results in terms of favorable response rates. As the trial was underpowered for survival analyses, conclusive data would require a larger randomized trial. Unless such a study is done, 3BE500P is the treatment of choice for metastatic NSGCT patients. PMID- 17351253 TI - Phase III study in stage IV non-small-cell lung cancer patients treated with two courses of cisplatin/gemcitabine followed by a randomization to three additional courses of the same combination or gemcitabine alone. AB - BACKGROUND: This randomised phase III study investigated if in responsive and stable disease (SD) stage IV patients after two courses of cisplatin and gemcitabine, single-agent gemcitabine (experimental arm) was not inferior in terms of overall survival (OS) to cisplatin-gemcitabine (standard arm). PATIENTS AND METHODS: Noninferiority was defined as an increase in the hazard of death (HR) < or = 1.33 in the experimental arm. From January 2001 to February 2004, 340 patients were registered and 250 were randomised. Cisplatin was administered on day 1 at 75 mg/m2 and Gemcitabine on days 1 and 8 at 1250 mg/m2 every 3 weeks. RESULTS: Response rate after two courses was 29%. The 1-year progression-free survival was 13% in both arms. One-year survival was 52% in the standard and 42% in the experimental arm for an HR of 1.21 [90% confidence interval (CI) 0.97 1.51]. Postprogression survival was in favour of the standard arm (HR 1.30, 95% CI 0.99-1.70, P = 0.051). Grades 3-4 toxicity favoured in the experimental arm. CONCLUSION: In responsive and SD patients with stage IV non-small-cell lung cancer it was not possible to demonstrate that three courses of gemcitabine alone are not inferior, in terms of OS, to the standard approach of three courses of cisplatin-gemcitabine. PMID- 17351254 TI - Quantitative real-time PCR analysis and microarray-based RNA expression of HER2 in relation to outcome. AB - BACKGROUND: Our aim was to use quantitative real-time PCR (Q-PCR) and RNA expression profiles (RNA-EPs) to investigate HER2 status in relation to outcome. PATIENTS AND METHODS: Cut-off levels for Q-PCR and RNA-EP were established in relation to immunohistochemistry (IHC) validated by FISH in a test set of frozen tissue samples from 40 primary breast cancers. The HER2 status was subsequently studied in another validation set of 306 tumors, where Q-PCR and RNA-EP results were compared with previously carried out IHC that we had validated by chromogenic in situ hybridization (CISH). RESULTS: Q-PCR and RNA-EP offered similar sensitivity (90% versus 77%), specificity (93% versus 95%), and negative (99% versus 98%) and positive (63% versus 61%) predictive values for HER2 determinations. Analyses of relapse-free survival (RFS) and overall survival on the basis of 5 and 10 years of follow-up indicated equivalent hazard ratios for all three techniques. In contrast to IHC/CISH, both Q-PCR and RNA-EP analyses of HER2 also gave statistically significant results regarding RFS and breast cancer corrected survival after 10 years of follow-up. CONCLUSION: The use of RNA-EP and Q-PCR to analyze HER2 in frozen and formalin-fixed breast cancer samples may be an alternate approach to IHC in combination with FISH/CISH. PMID- 17351255 TI - Gastrin-releasing peptide receptor as a molecular target in experimental anticancer therapy. AB - Over the last two decades, several lines of experimental evidence have suggested that the gastrin-releasing peptide (GRP) may act as a growth factor in many types of cancer. For that reason, gastrin-releasing peptide receptor (GRPR) antagonists have been developed as anticancer candidate compounds, exhibiting impressive antitumoral activity both in vitro and in vivo in various murine and human tumors. In this article, the GRPR cell surface expression profile in human malignancies is reviewed aiming at the identification of potential tumor types for future clinical trials with GRP analogues and antagonists. In this review, we summarize the current literature regarding the GRPR status in human malignancies. Source data were obtained by searching all published material available through Medline, PubMed and relevant articles from 1971 to 2006. The data available demonstrated a high expression of GRPRs in a large spectrum of human cancers, demonstrating the potential relevance of this intracellular signaling pathway in various human tumor models. The GRPR may be an interesting target for therapeutic intervention in human malignancies, as carriers for cytotoxins, immunotoxins or radioactive compounds, being also a potential tool for tumor detection. PMID- 17351256 TI - Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer. AB - BACKGROUND: The purpose of the study was to evaluate the efficacy of weekly paclitaxel (Taxol) in advanced esophageal cancer. PATIENTS AND METHODS: One hundred and two patients with advanced esophageal cancer were treated with paclitaxel 80 mg/m2 weekly over a 1-h infusion. One cycle was defined as 4 weeks of therapy. Ninety-five patients were assessable for toxicity and 86 patients who completed at least two cycles of treatment were assessable for response. Sixty six patients had adenocarcinoma (66%) and 65 patients (68%) had no prior chemotherapy. RESULTS: A median of three cycles was delivered (range 1-11). Partial responses (PRs) were seen in 11 patients [13%, 95% confidence interval (CI) 6% to 20%]. In patients without prior chemotherapy, PRs were seen in 10 patients (15%, 95% CI 6% to 24%), with comparable response in adenocarcinoma (8/50, 16%) and squamous carcinoma (2/15, 13%). Limited response was seen in patients with prior chemotherapy (1/21, 5%). The median duration of response was 172 days. The median survival was 274 days. Therapy was well tolerated with minimal hematologic or grade 3 or 4 toxicity. CONCLUSION: Weekly paclitaxel has limited activity in esophageal cancer. The median survival, modest activity, and tolerance of therapy indicate that weekly paclitaxel may be an option in patients unable to tolerate combination chemotherapy. PMID- 17351257 TI - Potential risks and benefits of radiation therapy as adjuvant treatment in patients with low-risk carcinoma of the mammary gland: taking cutaneous postradiation angiosarcoma as an opportunity for a critical appraisal of postoperative radiotherapy. PMID- 17351258 TI - Breast cancer in elderly women: a different reality? Results from the NORA study. AB - BACKGROUND: The incidence of breast cancer increases with age, and the disease affects many older women; however, attitudes about prevention and treatment of breast cancer vary based on the patient's age. Older women have less access to clinical trials and fewer opportunities for treatment with innovative therapies. The National Oncological Research observatory on Adjuvant therapy in breast cancer (NORA) study was a cohort study designed to obtain information about adjuvant strategies for treatment of breast cancer after surgery, patterns of recurrence, and possible correlations between cancer-related events and biological factors. PATIENTS AND METHODS: This report describes patient characteristics, disease status, and local and systemic adjuvant treatments in a population of breast cancer patients aged >or=65 years. The NORA study consecutively enrolled >3500 patients from 2000 through 2002 at 77 Italian hospitals; of these, 1085 were aged >or=65 years. Data on patient characteristics, cancer presentation, and treatments were analyzed to identify possible relationships between these factors and age. RESULTS: The findings indicate that age is significantly related to later diagnosis and different patterns of treatment. Choice of adjuvant systemic treatment was primarily related to hormone receptor status and tumor stage but was strongly influenced by the patient's age; there was a proportional relationship between endocrine treatment and increasing age. Cyclophosphamide, methotrexate, and 5-fluorouracil as well as anthracyclines were widely used, but the use of taxanes was limited to a very small percentage of patients. CONCLUSIONS: The findings of the NORA study may help to change attitudes that currently exclude a significant proportion of breast cancer patients from secondary prevention policies, more active treatment strategies, and clinical research trials based on age. PMID- 17351259 TI - Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer. AB - PURPOSE: Recent studies have indicated that expression of chemokine receptors CXCR4 and CCR7 could be an indicator of the metastatic potential of breast cancer. Expression of CXCR4 and CCR7 along with the biomarkers HER2-neu and epidermal growth factor receptor (EGFR) was investigated in inflammatory breast cancer (IBC) to evaluate their prognostic implications. EXPERIMENTAL DESIGN: CXCR4, CCR7, and EGFR were evaluated by immunohistochemical staining (IHC) of paraffin-embedded tissue sections. HER2-neu amplification was assessed by FISH and/or IHC. All patients received chemotherapy, surgery, and radiation. RESULTS: Forty-four cases diagnosed with IBC from 1994 to 2002 were included in the study. In all, 18 (40.9%) patients had positive CXCR4, 10 (22.7%) had positive CCR7, 21 (47.7%) had positive HER2-neu, and EGFR was positive in 12 of 40 patients (30%). The 5-year overall survival (OS) was 24.8% for CXCR4-positive disease versus 42.3% for CXCR4-negative patients (P = 0.53) and 20.0% for CCR7-positive disease versus 41.9% for CCR7-negative patients (P = 0.24). EGFR-positive disease had significantly worse OS compared with EGFR-negative disease (P = 0.01). CONCLUSIONS: These data demonstrate the expression of growth factor and chemokine receptors in IBC. The expression of these receptors is associated with increased risk of recurrence and death, and thus, they may represent potential therapeutic targets in IBC. PMID- 17351260 TI - Monitoring of renal function in cancer patients: an ongoing challenge for clinical practice. AB - BACKGROUND: Renal impairment (RI) has been shown to be one major risk factor in a number of diseases and is associated with a dismal clinical outcome. However, the influence of milder degrees of renal disease is less well defined, particularly not in patients with malignant diseases. PATIENTS AND METHODS: We analyzed 167 patients with solid tumors and hematological malignancies. Besides disease specific parameters, serum creatinine, cystatin C and the estimated glomerular filtration rate (eGFR) ['modification of diet in renal disease' equation (MDRD)/Cockcroft-Gault (CG)] were determined. Patients were compared within eGFR, creatinine and cystatin C groups. RESULTS: The median MDRD, CG, creatinine and cystatin C levels of all patients were 88 ml/min/1.73 m2, 89 ml/min, 1 mg/dl and 0.9 mg/l, respectively. Patients with chronic kidney disease stage 2 still showed normal creatinine and cystatin levels of 1 mg/dl and 1.1 mg/l, respectively, although mild RI was frequent. Those cancer patients with decreased eGFR (MDRD) (<60 ml/min/1.73 m2) had increased odds ratios (ORs) to have more concurrent diagnoses [OR 3.4; 95% confidence interval (CI) 1.5-8.1], a body mass index >24 kg/m2 (OR 2.1; 95% CI 1.0-4.5) and an elevated (> 245 pg/ml) pro-brain natriuretic peptide level (proBNP) (OR 9.2; 95% CI 3.0-28.3). CONCLUSIONS: These observations suggest that grouping cancer patients according to renal function, especially eGFR, may be one way to determine specific risk groups. PMID- 17351261 TI - Uterine temporal response to acute exposure to 17alpha-ethinyl estradiol in the immature rat. AB - The rat uterus responds to acute estrogen treatment with a series of well characterized physiological responses; however, the gene expression changes required to elicit these responses have not been fully characterized. In order to understand early events induced by estrogen exposure in vivo, we evaluated the temporal gene expression in the uterus of the immature rat after a single dose of 17 alpha-ethinyl estradiol (EE) by microarray analysis, evaluating the expression of 15,923 genes. Immature 20-day-old rats were exposed to a single dose of EE (10 microg/kg), and the effects on uterine histology, weight, and gene expression were determined after 1, 2, 8, 24, 48, 72, and 96 h. EE induced changes in the expression of 3867 genes, at least at one time point (p < or = 0.0001), and at least 1.5-fold (up- or downregulated). Specifically, the expression of 8, 116, 3030, 2076, 381, 445, and 125 genes was modified at 1, 2, 8, 24, 48, 72, or 96 h after exposure to EE, respectively (p < or = 0.0001, t-test). At the tissue and organ level, a clear uterotrophic response was elicited by EE after only 8 h, reaching a maximum after 24 h and remaining detectable even after 96 h of exposure. The uterine phenotypic changes were induced by sequential changes in the transcriptional status of a large number of genes, in a program that involves multiple molecular pathways. Using the Gene Ontology to better understand the temporal response to estrogen exposure, we determined that the earliest changes were in the expression of genes whose products are involved in transcriptional regulation and signal transduction, followed by genes implicated in protein synthesis, energy utilization, solute transport, cell proliferation and differentiation, tissue remodeling, and immunological responses among other pathways. The compendium of genes here presented represents a comprehensive compilation of estrogen-responsive genes involved in the uterotrophic response. PMID- 17351262 TI - Preclinical cardiovascular risk assessment in modern drug development. PMID- 17351263 TI - Functional analysis of hairpin ribozyme active site architecture. AB - The hairpin ribozyme is a small catalytic motif found in plant satellite RNAs where it catalyzes a reversible self-cleavage reaction during processing of replication intermediates. Crystallographic studies of hairpin ribozymes have provided high resolution views of the RNA functional groups that comprise the active site and stimulated biochemical studies that probed the contributions of nucleobase functional groups to catalytic chemistry. The dramatic loss of activity that results from perturbation of active site architecture points to the importance of positioning and orientation in catalytic rate acceleration. The current study focuses on the network of noncovalent interactions that align nucleophilic and leaving group oxygens in the orientation required for the S(N)2 type reaction mechanism and orient the active site nucleobases near the reactive phosphate to facilitate catalytic chemistry. Nucleotide modifications that alter or eliminate individual hydrogen bonding partners had different effects on the activation barrier to catalysis, the stability of ribozyme complexes in the ground state, and the internal equilibrium between cleavage and ligation of bound products. Furthermore, substitution of hydrogen bond donors and acceptors with seemingly equivalent pairs sometimes had very different functional consequences. These biochemical analyses augment high resolution structural information to provide insights into the functional significance of active site architecture. PMID- 17351264 TI - A case control study of lung cancer and exposure to chrysotile and amphibole at a slovenian asbestos-cement plant. AB - A lung cancer case-control study was conducted in a Slovenian asbestos-cement factory for which unusually good records of asbestos exposures were available. The cohort consisted of all 6714 workers employed at the Salonit Anhovo factory after 31 December 1946 who worked there for at least one day between 1964 and 1994. Fifty-eight histologically confirmed cases of primary lung cancer and 290 controls were selected from the cohort. Working life exposure histories to amphibole and chrysotile forms of asbestos were estimated separately. Airborne asbestos concentrations were low. For example, the arithmetic mean exposure to all forms of asbestos in the highest exposure period (1947-1971) was 1.2 f/cm(3). Chrysotile asbestos made up about 90% of this exposure (mean 1.1 f/cm(3)), whereas amphibole accounted for 10% (0.1 f/cm(3)). Comparing those above and below the 90 percentile of cumulative exposure, the odds ratios for all asbestos, chrysotile and amphibole were 1.5, 1.6 and 2.0, respectively, but confidence intervals were wide. There are only a few asbestos-lung cancer studies with high quality exposure data and exposures in this low range. Though imprecise, the findings are important to the ongoing debate about asbestos risks. PMID- 17351265 TI - Ventilation equations for improved exothermic process control. AB - Exothermic or heated processes create potentially unsafe work environments for an estimated 5-10 million American workers each year. Excessive heat and process contaminants have the potential to cause acute health effects such as heat stroke, and chronic effects such as manganism in welders. Although millions of workers are exposed to exothermic processes, insufficient attention has been given to continuously improving engineering technologies for these processes to provide effective and efficient control. Currently there is no specific occupational standard established by OSHA regarding exposure to heat from exothermic processes, therefore it is important to investigate techniques that can mitigate known and potential adverse occupational health effects. The current understanding of engineering controls for exothermic processes is primarily based on a book chapter written by W. C. L. Hemeon in 1955. Improvements in heat transfer and meteorological theory necessary to design improved process controls have occurred since this time. The research presented involved a review of the physical properties, heat transfer and meteorological theories governing buoyant air flow created by exothermic processes. These properties and theories were used to identify parameters and develop equations required for the determination of buoyant volumetric flow to assist in improving ventilation controls. Goals of this research were to develop and describe a new (i.e. proposed) flow equation, and compare it to currently accepted ones by Hemeon and the American Conference of Governmental Industrial Hygienists (ACGIH). Numerical assessments were conducted to compare solutions from the proposed equations for plume area, mean velocity and flow to those from the ACGIH and Hemeon. Parameters were varied for the dependent variables and solutions from the proposed, ACGIH, and Hemeon equations for plume area, mean velocity and flow were analyzed using a randomized complete block statistical design (ANOVA). Results indicate that the proposed plume mean velocity equation provides significantly greater means than either the ACGIH or Hemeon equations throughout the range of parameters investigated. The proposed equations for plume area and flow also provide significantly greater means than either the ACGIH or Hemeon equations at distances >1 m above exothermic processes. With an accurate solution for the total volumetric flow, ventilation engineers and practicing industrial hygienists are equipped with the necessary information to design and size hoods, as well as place them at an optimal distance from the source to provide adequate control of the rising plume. The equations developed will allow researchers and practitioners to determine the critical control parameters for exothermic processes, such as the exhaust flow necessary to improve efficacy and efficiency, while ensuring adequate worker protection. PMID- 17351266 TI - Evaluating fungal populations by genera/species on wide body commercial passenger aircraft and in airport terminals. AB - Given the potential health effects of fungi and the amount of time aircrew and passengers spend inside aircraft, it is important to study fungal populations in the aircraft environment. Research objectives included documenting the genera/species of airborne culturable fungal concentrations and total spore concentrations on a twin-aisle wide body commercial passenger aircraft. Twelve flights between 4.5 and 6.5 h in duration on Boeing 767 (B-767) aircraft were evaluated. Two air cooling packs and 50% recirculation rate (i.e. 50:50 mix of outside air and filtered inside air) were utilized during flight operations. Passenger occupancy rates varied from 67 to 100%. N-6 impactors and total spore traps were used to collect sequential, triplicate air samples in the front and rear of coach class during six sampling intervals throughout each flight: boarding, mid-climb, early cruise, mid-cruise, late cruise and deplaning. Comparison air samples were also collected inside and outside the airport terminals at the origin and destination cities resulting in a total of 522 culturable and 517 total spore samples. A total of 45 surface wipe samples were collected using swabs onboard the aircraft and inside the airport terminals. A variety of taxa were observed in the culturable and total spore samples. A frequency analysis of the fungal data indicated that Cladosporium, Aspergillus and Penicillium were predominant genera in the culturable samples whereas Cladosporium, Basidiospores and Penicillium/Aspergillus were predominant in the total spore samples. Fungal populations observed inside the aircraft were comprised of similar genera, detected significantly less frequently and with lower mean concentrations than those observed in typical office buildings. Although sources internal to the aircraft could not be ruled out, our data demonstrate the importance of passenger activity as the source of the fungi observed on aircraft. Isolated fungal peak events occurred occasionally when concentrations of a particular genus or species rose sharply inside the cabin for a limited period. Overall, our research demonstrates that on the sampled flights the B-767 filtration system operated efficiently to remove fungal spores when two air cooling packs and 50% recirculation rate were utilized during flight operations. PMID- 17351267 TI - Tracing past human male movements in northern/eastern Africa and western Eurasia: new clues from Y-chromosomal haplogroups E-M78 and J-M12. AB - Detailed population data were obtained on the distribution of novel biallelic markers that finely dissect the human Y-chromosome haplogroup E-M78. Among 6,501 Y chromosomes sampled in 81 human populations worldwide, we found 517 E-M78 chromosomes and assigned them to 10 subhaplogroups. Eleven microsatellite loci were used to further evaluate subhaplogroup internal diversification. The geographic and quantitative analyses of haplogroup and microsatellite diversity is strongly suggestive of a northeastern African origin of E-M78, with a corridor for bidirectional migrations between northeastern and eastern Africa (at least 2 episodes between 23.9-17.3 ky and 18.0-5.9 ky ago), trans-Mediterranean migrations directly from northern Africa to Europe (mainly in the last 13.0 ky), and flow from northeastern Africa to western Asia between 20.0 and 6.8 ky ago. A single clade within E-M78 (E-V13) highlights a range expansion in the Bronze Age of southeastern Europe, which is also detected by haplogroup J-M12. Phylogeography pattern of molecular radiation and coalescence estimates for both haplogroups are similar and reveal that the genetic landscape of this region is, to a large extent, the consequence of a recent population growth in situ rather than the result of a mere flow of western Asian migrants in the early Neolithic. Our results not only provide a refinement of previous evolutionary hypotheses but also well-defined time frames for past human movements both in northern/eastern Africa and western Eurasia. PMID- 17351268 TI - An analytical model for calculating microdosimetric distributions from heavy ions in nanometer site targets. AB - The analytical model of Xapsos used for calculating microdosimetric spectra is based on the observation that straggling of energy loss can be approximated by a log-normal distribution of energy deposition. The model was applied to calculate microdosimetric spectra in spherical targets of nanometer dimensions from heavy ions at energies between 0.3 and 500 MeV amu(-1). We recalculated the originally assumed 1/E(2) initial delta electrons spectrum by applying the Continuous Slowing Down Approximation for secondary electrons. We also modified the energy deposition from electrons of energy below 100 keV, taking into account the effective path length of the scattered electrons. Results of our model calculations agree favourably with results of Monte Carlo track structure simulations using MOCA-14 for light ions (Z = 1-8) of energy ranging from E = 0.3 to 10.0 MeV amu(-1) as well as with results of Nikjoo for a wall-less proportional counter (Z = 18). PMID- 17351269 TI - IAEA/IDEAS intercomparison exercise on internal dose assessment. AB - An Internet based intercomparison exercise on assessment of occupational exposure due to intakes of radionuclides has been performed to check the applicability of the 'General Guidelines for the Assessment of Internal Dose from Monitoring Data' developed by the IDEAS group. There were six intake cases presented on the Internet and 81 participants worldwide reported solutions to these cases. Results of the exercise indicate that the guidelines have a positive influence on the methodologies applied for dose assessments and, if correctly applied, improve the harmonisation of assessed doses. PMID- 17351270 TI - Radiation-induced DNA damage responses. AB - The amazing feature of ionising radiation (IR) as a DNA damaging agent is the range of lesions it induces. Such lesions include base damage, single strand breaks (SSBs), double strand breaks (DSBs) of varying complexity and DNA cross links. A range of DNA damage response mechanisms operate to help maintain genomic stability in the face of such damage. Such mechanisms include pathways of DNA repair and signal transduction mechanisms. Increasing evidence suggests that these pathways operate co-operatively. In addition, the relative impact of one mechanism over another most probably depends upon the cell cycle phase and tissue type. Here, the distinct damage response pathways are reviewed and the current understanding of the interplay between them is considered. Since DNA DSBs are the major lethal lesion induced by IR, the focus lies in the mechanisms responding to direct or indirectly induced DSBs. PMID- 17351271 TI - Point: Recent long-term clinical studies support an enhanced role for thiazolidinediones in the management of type 2 diabetes. PMID- 17351272 TI - Safe at school: a Virginia experience. AB - OBJECTIVE: The Commonwealth of Virginia passed legislation in 1999 requiring nonmedical school personnel to assist students with the management of type 1 diabetes when school nurses were unavailable. This study was designed to determine which school personnel in Virginia currently assist type 1 diabetic students with insulin administration and management of hypoglycemia and to determine if these students are being cared for in a safe manner. RESEARCH DESIGN AND METHODS: Parents of children with type 1 diabetes who attended public school in Virginia during the previous year and who were receiving their diabetes care at the University of Virginia diabetes clinics were asked to participate in an anonymous survey. The survey asked parents which school personnel were responsible for their child's diabetes care while at school and which persons helped with specific care tasks including blood glucose monitoring, insulin administration, and assistance with treatment of hypoglycemia. Questions were asked regarding the occurrence and treatment of hypoglycemia and any adverse effects of such treatment. RESULTS: A total of 185 parents whose children attended 153 different schools responded, 69% of whom reported that a full-time school nurse was assigned to their child's school. In other schools, teachers, administrators, coaches, and cafeteria workers supplemented part-time nurses in assisting students with diabetes management tasks. Although hypoglycemia was not a rare event (75% of students experienced a median of five episodes per year), only one severe event requiring the use of glucagon was reported. In that case, glucagon was administered appropriately by a part-time school nurse, and the student experienced no adverse effects related to the treatment. CONCLUSIONS: Students with type 1 diabetes can be cared for safely during the school day by a variety of trained medical and nonmedical personnel. The occurrence of one severe hypoglycemic event among 185 students suggests that as many as 3% of students could experience severe hypoglycemia in a given school year. Legislation that permits nonmedical school personnel to assist students with their diabetes management could make the diabetic children's school day safer and improve their overall glucose control. PMID- 17351273 TI - Leisure-time physical activity is associated with the metabolic syndrome in type 1 diabetes: effect of the PPARgamma Pro12Ala polymorphism: the FinnDiane Study. PMID- 17351274 TI - Association of A1C with cardiovascular disease and metabolic syndrome in Asian Indians with normal glucose tolerance. AB - OBJECTIVE: This study examines the association of A1C with cardiovascular disease (CVD) risk factors, coronary artery disease (CAD), and metabolic syndrome in Asian Indians with normal glucose tolerance (NGT). RESEARCH DESIGN AND METHODS: This cross-sectional study recruited subjects from phase III of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study in a representative population of Chennai (formerly Madras) in South India, conducted between January 2003 and June 2004. Included were 1,644 subjects with NGT, i.e., fasting plasma glucose <100 mg/dl (5.6 mmol/l) and 2-h postload plasma glucose <140 mg/dl (7.8 mmol/l). A1C was measured using the Biorad Variant machine. Metabolic syndrome was defined based on modified Adult Treatment Panel III guidelines. RESULTS: The mean +/- SD A1C value in the study cohort was 5.5 +/- 0.4%. A1C showed a significant association with BMI (beta = 0.017, P < 0.001), systolic (beta = 0.002, P = 0.028) and diastolic (beta = 0.202, P = 0.017) blood pressure, waist circumference (beta = 0.007, P < 0.001), serum cholesterol (beta = 0.002, P < 0.001), triglycerides (beta = 0.001, P < 0.001), LDL cholesterol (beta = 0.002, P < 0.001), fasting insulin (beta = 0.009, P < 0.001), and homeostasis model assessment of insulin resistance (beta = 0.047, P < 0.001) after adjusting for age and sex. Regression analysis showed that A1C had a strong association with metabolic syndrome that persisted after adjusting for age and sex (odds ratio [OR] 2.9 [95% CI 2.08-4.00]; P < 0.001). A1C also had a strong association with CAD (2.6 [1.23-5.63]; P = 0.01), but the significance was lost when adjusted for age and sex. CONCLUSIONS: There is a strong association of A1C with prevalent CVD risk factors in Asian-Indian subjects with NGT. PMID- 17351275 TI - Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant adults. AB - OBJECTIVE: Although weight loss interventions have been shown to reduce steatosis in nonalcoholic fatty liver disease (NAFLD), the impact of dietary macronutrient composition is unknown. We assessed the effect on serum alanine aminotransferase (ALT) concentrations of two hypocaloric diets varying in amounts of carbohydrate and fat in obese insulin-resistant individuals, a population at high risk for NAFLD. RESEARCH DESIGN AND METHODS: Post hoc analysis of ALT concentrations was performed in 52 obese subjects with normal baseline values and insulin resistance, as quantified by the steady-state plasma glucose (SSPG) test, who were randomized to hypocaloric diets containing either 60% carbohydrate/25% fat or 40% carbohydrate/45% fat (15% protein) for 16 weeks. The primary end point was change in ALT, which was evaluated according to diet, weight loss, SSPG, and daylong insulin concentrations. RESULTS: Although both diets resulted in significant decreases in weight and SSPG, daylong insulin, and serum ALT concentrations, the 40% carbohydrate diet resulted in greater decreases in SSPG (P < 0.04), circulating insulin (P < 0.01), and ALT (9.5 +/- 9.4 vs. 4.2 +/- 8.3 units/l; P < 0.04) concentrations. ALT changes correlated with improvement in insulin sensitivity (P = 0.04) and daylong insulin (P < 0.01). Individuals with ALT concentrations above the proposed upper limits experienced significant declines in ALT, unlike those with lower ALT levels. CONCLUSIONS: In a population at high risk for NAFLD, a hypocaloric diet moderately lower in carbohydrate decreased serum ALT concentrations to a greater degree than a higher carbohydrate/low-fat diet, despite equal weight loss. This may result from a relatively greater decline in daylong insulin concentrations. Further research with histological end points is needed to further explore this finding. PMID- 17351276 TI - Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults. AB - OBJECTIVE: Accumulating research suggests low-circulating vitamin D concentrations, i.e., 25-hydroxyvitamin-D [25(OH)D], may be associated with an increased prevalence of metabolic syndrome; however, previous studies have not accounted for parathyroid hormone (PTH) levels. We examined the association of 25(OH)D and PTH with the prevalence of metabolic syndrome in a community-based cohort of older adults. RESEARCH DESIGN AND METHODS: Participants included 410 men and 660 women, 44-96 years old, who completed a follow-up clinic visit in 1997-1999 as part of the Rancho Bernardo Study. Sex-specific logistic regression models were fit to estimate the odds of ATP III (Adult Treatment Panel III) defined metabolic syndrome across quintiles of 25(OH)D and PTH, adjusting for age, season, and major lifestyle factors. RESULTS: In men, there was a significant trend (P = 0.03) of increasing adjusted odds for metabolic syndrome with increasing PTH concentrations, primarily due to an odds ratio of 2.02 (95% CI 0.96-4.24) in men in the top quintile (> or =63 ng/l) of PTH concentration. This association remained unchanged after taking into account 25(OH)D levels and excluding men with diabetes or impaired renal function; it was attenuated after adjustment for the homeostasis model assessment of insulin resistance. Neither PTH in women nor 25(OH)D levels in either sex was related to the metabolic syndrome. CONCLUSIONS: These findings suggest an increased risk of metabolic syndrome with elevated PTH levels in older men and no effect of 25(OH)D concentrations in either sex. The reason for the sex difference in the PTH metabolic syndrome association is unknown. Prospective studies are necessary to better determine the roles of 25(OH)D and PTH in the etiology of metabolic syndrome. PMID- 17351277 TI - Diabetes care in extended-care facilities: appropriate intensity of care? AB - OBJECTIVE: The American Diabetes Association (ADA) does not recognize different treatment goals for the institutionalized adult compared with the outpatient adult with diabetes, nor has it outlined specific recommendations for this population. The purpose of this study was to examine physician management of patients with type 1 and type 2 diabetes residing in extended-care facilities and to compare this management with ADA standards of care for the outpatient adult. RESEARCH DESIGN AND METHODS: This retrospective chart review included data from 108 residents with type 1 or type 2 diabetes at 11 extended health care facilities in the Midwestern U.S. and included a review of the medical problem list, medication list, laboratory reports, and all physician and consultation notes during the study period. RESULTS: Blood glucose was monitored in 98% of the subjects, and 38% met glucose goals. A1C goal was achieved in 67% of patients. Blood pressure was monitored in 94% of patients, with 55% meeting goal. Thirty one percent of patients had yearly lipids checked, 37% had annual electrocardiograms, 7% had urine analyzed for microalbuminuria, 42% were on aspirin, 87% received foot exams, 42% received dilated eye exams, 89% received influenza vaccinations, and 46% received pneumoccocal vaccinations. CONCLUSIONS: Care of the institutionalized elderly with diabetes fails to meet ADA standards of care for the outpatient adult. Separate practice guidelines are needed for people with diabetes who reside in extended care facilities in order to improve quality and consistency of care. PMID- 17351278 TI - Efonidipine simultaneously improves blood pressure, endothelial function, and metabolic parameters in nondiabetic patients with hypertension. PMID- 17351279 TI - Short-term weight change and the incidence of diabetes in midlife: results from the Australian Longitudinal Study on Women's Health. AB - OBJECTIVE: Although there is consensus that excess adiposity is strongly associated with type 2 diabetes, its relationship with weight change is less clear. This study investigates the relative impact of BMI at baseline and short term (2- or 3-year) weight changes on the incidence of diabetes. RESEARCH DESIGN AND METHODS: Prospective data were collected from a population-based cohort of middle-aged women participating in the Australian Longitudinal Study on Women's Health (n = 7,239 for this report). To date, participants have completed four mailed surveys (S1, 1996; S2, 1998; S3, 2001; and S4, 2004). Generalized estimating equations were used to model binary repeated-measures data to assess the impact of BMI at S1 and weight change (S1 to S2; S2 to S3) on 3-year incidence of diabetes at S3 and S4, respectively, adjusting for sociodemographic and lifestyle factors. RESULTS: BMI at S1 was strongly associated with the development of diabetes by S3 or S4. Compared with women who had a BMI <25 kg/m2, those with BMI > or =25 kg/m2 had higher incidence of diabetes (P < 0.0001), with odd ratios reaching 12.1 (95% CI 7.6-19.3) for women in the very obese group (BMI > or =35 kg/m2). There was no association between shorter-term weight gain or weight loss on first-reported diagnosis of diabetes (P = 0.08). CONCLUSIONS: Because women's risk of developing type 2 diabetes in midlife is more closely related to their initial BMI (when aged 45-50 years) than to subsequent short term weight change, public health initiatives should target the prevention of weight gain before and during early adulthood. PMID- 17351280 TI - The effect of beta-adrenergic and peroxisome proliferator-activated receptor gamma stimulation on target genes related to lipid metabolism in human subcutaneous adipose tissue. AB - OBJECTIVE: The sympathetic nervous system and thiazolidinediones control lipid metabolism and have been implicated in body weight regulation. This study was conducted to determine whether the simultaneous activation of these two signaling systems might synergize to exert beneficial effects on the expression of key genes involved in lipid metabolism and mitochondrial biogenesis in subcutaneous fat in nondiabetic subjects. RESEARCH DESIGN AND METHODS: A total of 57 women and men were randomized into four groups: 1) placebo/placebo (PP), 2) ephedrine HCl (25 mg, 3 times daily) plus caffeine (200 mg, 3 times daily)/placebo (ECP), 3) placebo/pioglitazone (45 mg) (PPio), and 4) ephedrine plus caffeine/pioglitazone (ECPio) for 16 weeks. Adipose tissue samples were obtained after 12 weeks of treatment to determine gene expression. RESULTS: Body fat decreased by 6.0 and 4.6% in the ECP and ECPio groups, respectively, while remaining unchanged in the PPio and PP groups. Triglyceride levels decreased by -7.7, -24, -15.2, and -41 mg/dl after 16 weeks treatment in the PP, PPio, ECP, and ECPio groups, respectively. This indicates that pioglitazone groups with or without EC (ephedrine HCl plus caffeine) decreased triglycerides, and EC groups with or without pioglitazone decreased body weight. The mRNA for sirtuin 1 and CD36 increased only in the ECPio group. Carnitine palmitoyltransferase-1, medium-chain acyl CoA dehydrogenase, and malonyl-CoA decarboxylase increased with PPio and ECPio. Stearoyl-CoA desaturase decreased with ECP. CONCLUSIONS: Combined activation of peroxisome proliferator-activated receptor-gamma and beta adrenergic receptors has beneficial effects on body weight, plasma triglycerides, and lipid metabolism in subcutaneous fat by increasing the expression of genes required for fatty acid catabolism. PMID- 17351281 TI - Additive effects of obesity and TCF7L2 variants on risk for type 2 diabetes among cardiac patients. PMID- 17351282 TI - Exercise capacity and body mass as predictors of mortality among male veterans with type 2 diabetes. AB - OBJECTIVE: To demonstrate the relation of exercise capacity and BMI to mortality in a population of male veterans with type 2 diabetes. RESEARCH DESIGN AND METHODS: After excluding two underweight patients (BMI <18.5 kg/m2), the study population comprised 831 consecutive patients with type 2 diabetes (mean age 61 +/- 9 years) referred for exercise testing for clinical reasons between 1995 and 2006. Exercise capacity was determined from a maximal exercise test and measured in metabolic equivalents (METs). Patients were classified both according to BMI category (18.5-24.9, 25.0-29.9, and > or =30 kg/m2) and by exercise capacity (<5.0 or > or =5.0 maximal METs). The association among exercise capacity, BMI, other clinical variables, and all-cause mortality was assessed by Cox proportional hazards. Study participants were followed for mortality up to 30 June 2006. RESULTS: During a mean follow-up of 4.8 +/- 3.0 years, 112 patients died, for an average annual mortality rate of 2.2%. Each 1-MET increase in exercise capacity conferred a 10% survival benefit (hazard ratio 0.90 [95% CI 0.82-0.98]; P = 0.01), but BMI was not significantly associated with mortality. After adjustment for age, ethnicity, examination year, BMI, presence of cardiovascular disease (CVD), and CVD risk factors, diabetic patients achieving <5 maximal METs were 70% more likely to die (1.70 [1.13-2.54]) than those achieving > or =5 maximal METs. CONCLUSIONS: There was a strong inverse association between exercise capacity and mortality in this cohort of men with documented diabetes, and this relationship was independent of BMI. PMID- 17351283 TI - A multicenter randomized controlled trial of motivational interviewing in teenagers with diabetes. AB - OBJECTIVE: We sought to examine the efficacy of motivational interviewing with teenagers aged 14-17 years with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a randomized controlled trial analyzed by intention to treat, 66 teenagers with type 1 diabetes attending diabetes clinics in South Wales, U.K., were randomly assigned to the intervention group (38) and control group (28). Teenagers in the intervention group received motivational interviewing, and the control group received support visits. All participants received individual sessions over 12 months. The main outcome measures assessed at baseline, 6, 12, and 24 months were serum A1C and psychosocial self-report questionnaires including quality of life and well-being measures. RESULTS: At 12 months, 60 patients had complete data. At the end of the intervention (12 months), the mean A1C in the motivational interviewing group was significantly lower than in the control group (P = 0.04), after adjusting for baseline values. At 24 months (when n = 47), this difference in A1C was maintained (P = 0.003). There were differences in psychosocial variables at 12 months, with the motivational interviewing group indicating more positive well-being, improved quality of life, and differences in their personal models of illness (all P < 0.01). Some of these differences were maintained at 24 months. CONCLUSIONS: Motivational interviewing can be an effective method of facilitating behavioral changes in teenagers with type 1 diabetes with subsequent improvement in their glycemic control. PMID- 17351284 TI - Metabolic syndrome in hypertensive patients: correlation between anthropometric data and laboratory findings. PMID- 17351285 TI - The underuse of screening services among elderly women with diabetes. AB - OBJECTIVE: To determine whether the use of nondiabetes-related preventive services (mammography, colorectal cancer screening, and bone density testing) among elderly diabetic women is different from the use among nondiabetic women. RESEARCH DESIGN AND METHODS: Using a representative sample of the U.S. elderly female population and the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare files, we identified women with or without diabetes who were > or =67 years of age on 1 January 1999. All women with a prior history of cancer were excluded. Bivariate and multivariate analyses were used to compare the rates of preventive service use and to understand the factors influencing their use in the next 2-4 years. RESULTS: Women with diabetes were less likely to have a mammogram (odds ratio [OR] 0.83 [95% CI 0.78-0.88]), colorectal cancer screening (0.79 [0.70-0.88]), and bone density testing (0.63 [0.58-0.69]). Women with diabetes seen by endocrinologists had significantly higher rates of bone density testing than women seen by primary care physicians. Women seen by obstetrician/gynecologists had the highest rates of use of all three services. CONCLUSIONS: Elderly women with diabetes are less likely to receive cancer and osteoporosis screening than women without diabetes. Physicians treating these patients need to assure that they receive all recommended preventive services appropriate for their age. Additional national guidelines, practice-based improvements, and patient education targeting those at greatest risk of not receiving these services may be needed to achieve parity. PMID- 17351286 TI - Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1/MAC25) is linked to endothelial-dependent vasodilation in high-ferritin type 2 diabetes. PMID- 17351287 TI - Adolescents at risk for MODY3 diabetes prefer genetic testing before adulthood. PMID- 17351288 TI - Counterpoint: A Diabetes Outcome Progression Trial (ADOPT): good for sulfonylureas? PMID- 17351289 TI - Reproducibility and validity of the Shanghai Men's Health Study physical activity questionnaire. AB - Reproducibility and validity of the physical activity questionnaire (PAQ) used in the Shanghai Men's Health Study (2003-2006, People's Republic of China) was evaluated in a random sample of 196 participants aged 40-74 years. Participants completed a PAQ at baseline and again 1 year later, 12 monthly 7-day physical activity recalls, and four quarterly 1-week physical activity logs. Reproducibility was evaluated by using the two PAQs and validity by comparing the PAQs with 1-year averages of the two criterion measures: 7-day physical activity recall and physical activity log. The PAQ had moderate to high reproducibility for measuring adult exercise participation (kappa = 0.60) and energy expenditure (r(s) = 0.68), nonexercise activities (correlation coefficients = 0.42-0.68), and total daily energy expenditure (r(s) = 0.68, kappa(quartiles) = 0.47). Correlations between the PAQ and criterion measures of adult exercise were 0.45 (7-day physical activity recall) and 0.51 (physical activity log) for the first PAQ and 0.62 (7-day physical activity recall) and 0.71 (physical activity log) for the second PAQ. Correlations between PAQ nonexercise activities and the physical activity log and 7-day physical activity recall were 0.31-0.86. Correlations for total energy expenditure were high (0.62-0.77). Results indicate that the Shanghai Men's Health Study PAQ has reasonable reproducibility and validity for classifying men by their level of exercise and nonexercise activities in this cohort. PMID- 17351291 TI - Pregnancy loss among pregnancies conceived through assisted reproductive technology, United States, 1999-2002. AB - Approximately 30% of pregnancies in the United States may end in miscarriage or stillbirth. Whether pregnancies conceived through assisted reproductive technology (ART) are at an increased risk of loss is inconclusive, and data on maternal age-, ART type-, and gestational age-specific risk of loss are limited. Data on 148,494 ART pregnancies conceived from 1999 through 2002 were analyzed by use of the Kaplan-Meier method to estimate risks of pregnancy loss after specified gestational ages (conditional risk) for 14 groups stratified by maternal age and ART procedure. Births, maternal deaths, and induced abortions were censored. The Kaplan-Meier estimate of total risk of pregnancy loss was 29% but ranged from 22% to 63% depending on patient age and ART procedure. By 6 weeks' gestation, 58% of all pregnancy losses occurred. Conditional risk of pregnancy loss ranged from 10% to 45% at 6 weeks' gestation and from 2% to 7% at the first trimester; it was less than 2% after 20 weeks' gestation. Results can be used to counsel ART patients and inform future research on the etiology of pregnancy loss. PMID- 17351290 TI - Age, Gene/Environment Susceptibility-Reykjavik Study: multidisciplinary applied phenomics. AB - In anticipation of the sequencing of the human genome and description of the human proteome, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES Reykjavik) was initiated in 2002. AGES-Reykjavik was designed to examine risk factors, including genetic susceptibility and gene/environment interaction, in relation to disease and disability in old age. The study is multidisciplinary, providing detailed phenotypes related to the cardiovascular, neurocognitive (including sensory), and musculoskeletal systems, and to body composition and metabolic regulation. Relevant quantitative traits, subclinical indicators of disease, and medical diagnoses are identified by using biomarkers, imaging, and other physiologic indicators. The AGES-Reykjavik sample is drawn from an established population-based cohort, the Reykjavik Study. This cohort of men and women born between 1907 and 1935 has been followed in Iceland since 1967 by the Icelandic Heart Association. The AGES-Reykjavik cohort, with cardiovascular risk factor assessments earlier in life and detailed late-life phenotypes of quantitative traits, will create a comprehensive study of aging nested in a relatively genetically homogeneous older population. This approach should facilitate identification of genetic factors that contribute to healthy aging as well as the chronic conditions common in old age. PMID- 17351292 TI - Growth trajectory matters: interpreting the associations among birth weight, concurrent body size, and systolic blood pressure in a cohort study of 378,707 Swedish men. AB - The interpretation of the inverse association of birth weight with adult blood pressure after adjustment for concurrent size has been debated. In a large sample (n = 378,707) of Swedish men aged 18 years, born between 1973 and 1984, the authors found considerable variation in birth weight within strata of identical adult body mass index (to the nearest kg/m(2); range: 17-33 kg/m(2)), weight (nearest kg; range: 52-100 kg), and height (nearest cm; range: 164-196 cm). The regression coefficient of systolic blood pressure on birth weight was inverse and the same within strata of identical body mass index (p(interaction) = 0.80), weight (p = 0.79), and height (p = 0.35). When the analyses were restricted to those who were born between 39 and 41 weeks' gestation, consistent inverse associations remained within strata of identical adult size. Findings were similar when hypertension (rather than mean systolic blood pressure) was the outcome. These findings demonstrate that, for male babies who grow to be the same size at age 18 years, those who were of lower birth weight have on average higher blood pressure and a greater risk of hypertension. They suggest that growth between conception and early adulthood has relevance to understanding the etiology and, hence, prevention of high blood pressure. PMID- 17351294 TI - Perceived racial discrimination and nonadherence to screening mammography guidelines: results from the race differences in the screening mammography process study. AB - The study objective was to determine whether perceived racial discrimination influenced nonadherence to screening mammography guidelines. Enrolled in this prospective study were 1,451 women aged 40-79 years who obtained an "index" screening mammogram at one of five urban hospitals in Connecticut between October 1996 and January 1998. This logistic regression analysis included 1,229 women (484 African American (39%), 745 White (61%)) who completed telephone interviews at baseline and follow-up (on average 29 months later). Perceived racial discrimination was measured as lifetime experience in seven possible situations. Approximately 42% of African-American women and 10% of White women reported lifetime racial discrimination. Perceived racial discrimination was not associated with nonadherence to age-specific mammography screening guidelines in unadjusted or multivariate-adjusted analyses. Although these negative findings may reflect the well-recognized problems associated with measurement of perceived discrimination, it is possible that women who recognize and report racial discrimination develop compensatory characteristics that enable positive health prevention behavior, in spite of their past experiences. PMID- 17351293 TI - Association of arsenic exposure during pregnancy with fetal loss and infant death: a cohort study in Bangladesh. AB - The authors evaluated the effect of arsenic exposure on fetal and infant survival in a cohort of 29,134 pregnancies identified by the health and demographic surveillance system in Matlab, Bangladesh, in 1991-2000. Arsenic exposure, reflected by drinking water history and analysis of arsenic concentrations in tube-well water used by women during pregnancy, was assessed in a separate survey conducted in 2002-2003. Data on vital events, including pregnancy outcome and infant mortality, were collected by monthly surveillance at the household level. The risk of fetal loss and infant death in relation to arsenic exposure was estimated by a Cox proportional hazards model. Drinking tube-well water with more than 50 microg of arsenic per liter during pregnancy significantly increased the risks of fetal loss (relative risk = 1.14, 95% confidence interval: 1.04, 1.25) and infant death (relative risk = 1.17, 95% confidence interval: 1.03, 1.32). There was a significant dose response of arsenic exposure to risk of infant death (p = 0.02). Women of reproductive age should urgently be prioritized for mitigation activities where drinking water is contaminated by arsenic. PMID- 17351295 TI - Crystal structure of YegS, a homologue to the mammalian diacylglycerol kinases, reveals a novel regulatory metal binding site. AB - The human lipid kinase family controls cell proliferation, differentiation, and tumorigenesis and includes diacylglycerol kinases, sphingosine kinases, and ceramide kinases. YegS is an Escherichia coli protein with significant sequence homology to the catalytic domain of the human lipid kinases. We have solved the crystal structure of YegS and shown that it is a lipid kinase with phosphatidylglycerol kinase activity. The crystal structure reveals a two-domain protein with significant structural similarity to a family of NAD kinases. The active site is located in the interdomain cleft formed by four conserved sequence motifs. Surprisingly, the structure reveals a novel metal binding site composed of residues conserved in most lipid kinases. PMID- 17351296 TI - Wnt signaling stimulates osteoblastogenesis of mesenchymal precursors by suppressing CCAAT/enhancer-binding protein alpha and peroxisome proliferator activated receptor gamma. AB - Mesenchymal precursor cells have the potential to differentiate into several cell types, including adipocytes and osteoblasts. Activation of Wnt/beta-catenin signaling shifts mesenchymal cell fate toward osteoblastogenesis at the expense of adipogenesis; however, molecular mechanisms by which Wnt signaling alters mesenchymal cell fate have not been fully investigated. Our prior work indicates that multipotent precursors express adipogenic and osteoblastogenic transcription factors at physiological levels and that ectopic expression of Wnt10b in bipotential ST2 cells suppresses expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) and increases expression of Runx2, Dlx5, and osterix. Here, we demonstrate that transient activation of Wnt/beta-catenin signaling rapidly suppresses C/EBPalpha and PPARgamma, followed by activation of osteoblastogenic transcription factors. Enforced expression of C/EBPalpha or PPARgamma partially rescues lipid accumulation and decreases mineralization in ST2 cells expressing Wnt10b, suggesting that suppression of C/EBPalpha and PPARgamma is required for Wnt/beta-catenin to alter cell fate. Furthermore, knocking down expression of C/EBPalpha, PPARgamma, or both greatly reduces adipogenic potential and causes spontaneous osteoblastogenesis in ST2 cells and mouse embryonic fibroblasts, suggesting that Wnt signaling alters the fate of mesenchymal precursor cells primarily by suppressing C/EBPalpha and PPARgamma. PMID- 17351297 TI - Polio eradication: window of opportunity! PMID- 17351298 TI - Control of anemia: the time to act is now. PMID- 17351300 TI - Low dose 'Sprinkles'-- an innovative approach to treat iron deficiency anemia in infants and young children. AB - Iron supplementation programs using pediatric tablets or drops have not been successful in the control of anemia amongst infants and children in India. Sprinkles is an innovative multi-micronutrient home fortification strategy to control iron deficiency and anemia. OBJECTIVE: We aimed to determine the hematologic response to different doses and forms of iron in Sprinkles and iron drops. SETTING: Twenty two villages of Vadu Rural Health Program, KEM Hospital, Pune. DESIGN: Double blind clustered randomized community-based trial. SUBJECTS: Children (n=432) aged 6 to 18 mo age with Hb between 70 to 100 g/L were enrolled. METHODS: Selected villages were randomized into 5 groups: Sprinkles 12.5, 20 or 30 mg ferrous fumarate, Sprinkles 20 mg micronized ferric pyrophosphate or drops 20 mg ferrous glycine sulphate (DROPS) for 8 weeks. Household socio-demographic information was collected at baseline. Side effects and compliance were monitored through weekly visits. Hemoglobin was estimated at baseline, 3 and 8 weeks. Ferritin was assessed at baseline and 8 weeks. RESULTS: Baseline characteristics were similar across all groups. Hemoglobin increased significantly (P<0.0001) in all groups at 8 weeks with no difference between groups. Ferritin increased (P<0.0001) significantly in all groups with no difference across the groups. Compliance (overall range: 42 to 62 %) was lowest for DROPS. Side effects were significantly higher among DROPS compared to Sprinkles (p>0.05). CONCLUSIONS: Sprinkles 12.5 mg FF dose is as efficacious as higher doses of iron in Sprinkles or DROPS in increasing hemoglobin. Sprinkles FF 12.5 mg is recommended as it has fewer reported side effects and better compliance compared to DROPS. PMID- 17351301 TI - Evaluation and management of hypertension. PMID- 17351302 TI - Moya Moya cases treated with encephaloduroarteriosynangiosis. AB - OBJECTIVE: To study neurological outcome of Moya Moya disease treated surgically with Encephaloduroarteriosynengopsis (EDAS). DESIGN: Prospective observational study. SETTINGS: Community and General with tertiary care facility. SUBJECTS: Eight children diagnosed with Moya Moya disease by Magnetic Resonance Angiogramover 4 years of period were selected for EDAS. Children who were not able to sustain surgery excluded from study. METHODS: Treatment modality selected were surgery in form of EDAS. After surgery subjects were followed up for minimum of 2 year period to know neurological out come. Outcome was reported as poor, fair, good and excellent. No statistical analysis performed due to small sample size. RESULTS: After surgery no episode of stroke or TIA was observed in any patient during 2 year follow up period and all patients are living without any new neurological deficit. CONCLUSION: Long term outcome of EDAS is promising. PMID- 17351303 TI - Primary vesicoureteral reflux in Iranian children. AB - BACKGROUND: Experience with vesicoureteral reflux (VUR) differs in different centers and there are plenty of controversies. OBJECTIVE: The aim of this study was to evaluate the outcome of primary VUR complications and the rate of recurrence of UTI. METHODS: The medical charts of all infants and children with primary VUR who were followed up by two nephrologist were reviewed. During 19 years (1985 to 2004), 330 patients (271 females, 59 males) with 496 refluxing ureters were followed up as primary VUR. RESULTS: The patients age at diagnosis was 54 days to 16 years (Mean: 4.1 years) and the mean duration of follow-up was 4.5 years. Urinary tract infection (UTI) was the presenting symptom in 95% and fever was recorded in 35% of cases. Frequencies of different grades of VUR at initial investigation were 10% 35% 30% 13% and 12% for grades I to V, respectively. Recurrence of UTI in VUR of grades I to V, were 22.2% 18.1% 20% 23.4% and 17.9% respectively. Follow-up voiding cystourethrogram revealed resolution of VUR in 55% improvement in 27.5%, no change in 12% and deterioration in 5.5% Complications such as chronic renal failure and hypertension were observed in 13 and 13 patients, respectively. Renal scarring was present in 52% of boys and 29% of girls. CONCLUSION: The present study indicates that symptomatic primary VUR is more common and has better prognosis in girls. Recurrence of UTI is not related to the grade of VUR. PMID- 17351304 TI - Issues in counseling for Down syndrome. AB - We studied the background information, concerns and specific queries of thirty four families of children with Down syndrome. Majority of the parents were aware that their child has Down syndrome and has or will have mental retardation. However, most of the families were ignorant about the lack of curative treatment, chromosomal nature of the disorder and prenatal screening and testing options. PMID- 17351306 TI - Recurrent acute disseminated encephalomyelitis. AB - Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating condition, which is usually monophasic. Recurrent ADEM is a much less characterized entity and its differentiation from multiple sclerosis (MS) poses a diagnostic challenge. We report a seven year old girl with recurrence of ADEM after 19 months and discuss the diagnostic issues involved. PMID- 17351305 TI - Seroprevalence of Chlamydia pneumoniae in asthmatic children from Northern India. AB - Serum from children with chronic persistent asthma was subjected to C. pneumoniae IgG antibody determination. C. pneumoniae IgG serology suggestive of persistent infection was significantly higher in chronic persistent asthma group than in the control group. Seropositivity was significantly more in moderate and severe persistent groups than in the control subjects. There was no evidence of acute C. pneumoniae infection (IgM serology done in duplicate) in acute exacerbations. PMID- 17351307 TI - Townes-Brocks syndrome with hypothyroidism. AB - Townes-Brocks syndrome (TBS) is an autosomal dominant disorder with multiple malformations and variable expression. Major findings include external ear anomalies, hearing loss, limb deformity, imperforate anus, and renal malformations. Hypothyroidism is not a recognized feature of TBS. We are reporting a case of TBS with hypothyroidism, a rare association. PMID- 17351308 TI - Volvulus complicating dextrogastria in an infant. AB - We report eventration of right hemi-diaphragm resulting in gastric volvulus of the right sided stomach in an infant. The diagnosis of this rare association was made with contrast CT scan. Patient was initially managed with reduction of stomach, plication of right hemi diaphragm, anterior gastropexy and Ladds procedure, but required re-laparotomy after two months for recurrent volvulus. PMID- 17351309 TI - PHACES syndrome with congenital hypothyroidism. AB - The acronym PHACE syndrome stands for Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta and other cardiac defects, Eye abnormalities, Sternal clefting and/or a supraumbilical raphe. We report a 20 day old neonate who presented with a large facial hemangioma and Dandy-Walker cyst. This case is unusual because the cyst was detected antenatally and there was associated congenital hypothyroidism, which has been described very rarely with this condition. PMID- 17351310 TI - Maffucci syndrome. PMID- 17351311 TI - Atypical presentation of atypical organism. PMID- 17351312 TI - Congenital mirror movements in a child with Chiari type 1 malformation. PMID- 17351313 TI - Ketamine. PMID- 17351314 TI - The WH index revisited. PMID- 17351315 TI - Relation between corticotropin-releasing hormone neuron number in the hypothalamic paraventricular nucleus and depressive state in Alzheimer's disease. AB - BACKGROUND/AIMS: Depression occurs in 20-50% of the Alzheimer disease (AD) patients. It is not known whether depression in AD shares its pathophysiology with depressive disorder. Previously we found a fourfold increase of corticotropin-releasing hormone (CRH)-immunoreactive (IR) neurons in the hypothalamic paraventricular nucleus in depression. The objective of the present study was to find out whether in depression in AD the same phenomenon of an increased number of CRH-IR neurons could be observed. METHODS: Post-mortem brain tissue was obtained from a cohort of 23 AD patients prospectively studied using the Cornell Scale for Depression in Dementia to measure depressive symptoms. The number of CRH-IR neurons was determined using immunocytochemistry and the Image Pro Plus analysis program. RESULTS: A significant positive correlation was found between the Cornell scores and the number of CRH-IR neurons (p = 0.039) in AD patients. CONCLUSION: These results suggest that depressive disorder and depression in AD share, at least partly, their pathophysiology. PMID- 17351316 TI - A preliminary study towards downregulation of murine bone marrow eosinophilopoiesis mediated by small molecule inhibition of interleukin-5 receptor alpha gene in vitro. AB - BACKGROUND: Bone marrow eosinophilopoiesis induced by IL-5 makes a major contribution to eosinophilic airway inflammation in asthma. Bone marrow CD(34)(+) cells expressing IL-5Ralpha may be eosinophil progenitors. However, research on the effect of blocking IL-5Ralpha expression on bone marrow eosinophilopoiesis has seldom been reported. OBJECTIVE: To explore the effect of inhibiting IL 5Ralpha expression with IL-5Ralpha short hairpin RNA-expressing vector on murine bone marrow eosinophilopoiesisin vitro. METHODS: We constructed 4 kinds of plasmid vectors that could express small molecule inhibition, short hairpin RNA, which targeted IL-5Ralpha (P-IL-5Ralpha), and selected an effective one by transfecting B lymphoma cells in vitro. We also constructed an adenovirus vector which was inserted into an effective template sequence (Ad-IL-5Ralpha). The bone marrow cells were obtained from healthy Balb/c mice, and cultured and transfected by Ad-IL-5Ralpha in vitro. The expression of IL-5Ralpha and the count of newly produced eosinophils were detected in the cultured bone marrow cells. RESULTS: We found that P-IL-5Ralpha-3 targeted at the sequence of CAG CTG CCT GGT TCG TCT T markedly suppressed the IL-5Ralpha expression in the B lymphoma cellsin vitro. Ad IL-5Ralpha could suppress the IL-5Ralpha expression of murine bone marrow cellsin vitro and it could also significantly decrease the IL-5-induced eosinophilia in the cultured bone marrow cells. CONCLUSION: These results indicate that the blocking of IL-5Ralpha expression by small molecule inhibition can help to effectively decrease murine bone marrow eosinophilopoiesis, and that bone marrow may be used as a critical target organ in the diseases involved in eosinophilia, such as asthma. PMID- 17351317 TI - Utility of the Bender Gestalt Test for differentiation of dementia with Lewy bodies from Alzheimer's disease in patients showing mild to moderate dementia. AB - AIMS: We examined the utility of the Bender Gestalt Test (BGT) for the differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD), comparing BGT scores between DLB and AD patients showing mild to moderate dementia. METHODS: Eighteen DLB patients, 36 AD patients controlled by age, years of education, Clinical Dementia Rating and Mini Mental State Examination scores, and 21 nondemented elderly participants controlled by age and years of education were subjected to the BGT. Their BGT performances were scored according to the Pascal-Suttell method. RESULTS: The DLB group showed significantly higher (that is worse) BGT scores than the other groups. When a cutoff point of 98 was used to differentiate DLB from AD, the patients exceeding 98 were 94% in the DLB group, 17% in the AD group and 0% in the control group. The sensitivity and specificity of this cutoff point were 0.94 and 0.89, respectively. CONCLUSION: The BGT is a useful neuropsychological test to differentiate DLB from AD. PMID- 17351318 TI - Screening of cognitive impairment in chronic obstructive pulmonary disease. AB - Cognitive dysfunction is common and clinically important in severe chronic obstructive pulmonary disease (COPD). We investigated the diagnostic accuracy of the Mini Mental State Examination (MMSE) and Instrumental Activities of Daily Living (IADL) scale in screening severe cognitive dysfunction in 149 patients with COPD, mean age 69.3+/-8.5 years, forced expiratory volume in 1 s=36.6+/ 17.8% of the predicted. Patients underwent the MMSE and an in-depth neuropsychological assessment based upon the Mental Deterioration Battery (MDB). The 5-item IADL scale was assessed. The sample was randomly divided into a training (n=73) and a testing (n=76) population. The diagnostic accuracy of MMSE, IADL scale or both versus cognitive dysfunction corresponding to abnormal performance in 3 or more MDB tests was assessed in the training population and the model obtained was tested in the testing population. The combination of MMSE<24 and dependence in at least 1 IADL had better diagnostic accuracy than either MMSE or IADL, with sensitivity=52.4, specificity=82.7, positive predictive value=55.0% and negative predictive value=81.1% in the testing population. MMSE and the 5-item IADL scale can be used to exclude, but not to detect cognitive dysfunction in COPD patients. A confirmatory cognitive test should be administered to patients with an MMSE score of <24 and who are dependent in at least 1 IADL. PMID- 17351319 TI - Deficits in facial emotion processing in mild cognitive impairment. AB - BACKGROUND: Patients with Alzheimer disease consistently demonstrate impaired performance on tests of facial emotion processing. However, it remains unclear how early in the neurodegenerative process these deficits emerge. METHODS: We approached this question by examining facial emotional processing in a 'pre dementia' condition, amnestic mild cognitive impairment (MCI). Nine single-domain amnestic MCI subjects, 14 multiple-domain amnestic MCI subjects (MCI-MD), and 68 normal control subjects were assessed with the Florida Affect Battery. RESULTS: After adjustment for age and gender, analyses of performance across the facial affect processing subtests of the Florida Affect Battery demonstrated intact performance in the single-domain MCI group but significantly impaired performance in the MCI-MD group, particularly on a test of facial affect discrimination. Within the MCI-MD group, men performed disproportionately worse than women. Performance on facial affect discriminations in the MCI-MD group correlated most robustly with performance on tests of frontal/executive function. CONCLUSION: These data suggest that facial emotion processing can be impaired in MCI prior to the more marked cognitive deficits seen with clinically diagnosed Alzheimer disease. PMID- 17351320 TI - Cognitive changes in Parkinson's disease patients with visual hallucinations. AB - OBJECTIVE: To evaluate the decline in specific neuropsychological functions in nondemented Parkinson's disease (PD) patients with a history of visual hallucinations (VH). METHODS: Twenty PD patients with VH, 20 PD patients without VH and 18 normal controls were followed up over a 1-year period and assessed for cognitive decline. RESULTS: Forty-five percent of nondemented hallucinating PD patients developed dementia during the 1-year period between baseline and follow up evaluations. Of the nondemented hallucinating PD patients nearly 70% showed impairment in multiple cognitive domains. The progressive decline in hallucinating PD patients affected mainly visual memory for faces and visuoperceptive-visuospatial functions. CONCLUSION: Our results support a fast impairment of complex visual functions in hallucinating PD patients, but also a progressive decline in multiple cognitive domains, which have been identified as a risk of developing dementia in PD. PMID- 17351321 TI - Diagnostic value of the Reflux Disease Questionnaire in general practice. AB - OBJECTIVES: This study determined the diagnostic and therapeutic response of the Reflux Disease Questionnaire (RDQ) using the symptom association probability (SAP) as reference. In addition, the RDQ's construct validity and its relationship to quality of life (QOL) were ascertained. METHODS: Seventy-four patients with GORD symptoms (age 51 years (22-78); male 62%) derived from primary care completed the RDQ, GSRS and QOLRAD before and after a 2 weeks' course of esomeprazole 40 mg daily. The SAP was determined by a 24-hour pH recording before PPI treatment. The diagnostic abilities of the RDQ (total and 4 dimensions scores) were assessed with the area under the curve (AUC) of a receiver operating curve. RDQ scores before and after PPI treatment were compared with Wilcoxon tests. Multiple linear regressions assessed the RDQ's construct validity (GSRS) and relationship to QOL (QOLRAD). RESULTS: The AUCs were low for all RDQ dimensions (AUC <0.6). In the SAP-positive patients all RDQ dimensions improved (p < 0.0001) while the scores of the SAP negatives did not (heartburn p < 0.01; GORD and total score p < 0.05; regurgitation and dyspepsia n.s.). The RDQ was related to the total and reflux GSRS dimensions while the food and drink QOL dimension was linearly associated with the RDQ. CONCLUSIONS: The RDQ is a valid and reliable questionnaire with excellent construct validity and a good relationship to QOL. The diagnostic value of the RDQ in primary care is limited, but combination with an additional PPI treatment course might improve the RDQ's ability to discriminate GORD patients according to their SAP outcome. PMID- 17351322 TI - Relationships between the autonomic nervous system, humoral factors and immune functions in the intestine. AB - The mammalian intestinal epithelium is a unique model for studying cellular differentiation since it undergoes continuous and rapid renewal. Substantial new information has accumulated on the mechanisms of regulation of the gene expression (e.g. Wnt, Hedgehog, bone morphogenic proteins), and the cell proliferation and apoptosis of the intestine. New knowledge has been gained in areas of genetics, central nervous system and enteric nervous system neurotransmitters (e.g. serotonin, corticotrophin-releasing factor, endogenous cannabinoid system, pathogen associated molecular patterns) of motility, sensitivity and secretion, the effect of altered mucosal inflammation on cytokine and paracrine activation, and neural sensitization, postinfectious disorders, the influence of psychologic stress on gut functioning through alterations in regulatory pathways, and improved accuracy of diagnosis both at the gut and brain level. In addition, acknowledgement of these mechanisms might help to develop strategies for therapy of neuronal abnormalities, which cause different gastrointestinal disease (e.g. irritable bowel syndrome, Crohn's disease). The present review focuses on the relationships between the gene expression and the intestine, and furthermore, presents the evidence and gastrointestinal diseases of the autonomic nervous system, the humoral factors, and the immune functions related intestinal proliferation and apoptosis. PMID- 17351323 TI - Flow and pressure during liver preservation under ex situ and in situ perfusion with University of Wisconsin solution and histidine-tryptophan-ketoglutarate solution. AB - Effective preservation of liver grafts is the first essential step for successful liver transplantation. Insufficient perfusion leads to ischemic-type biliary lesions after transplantation. Perfusion of the graft can be performed either in situ or ex situ, with gravity flow or pressure-controlled. Mainly University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are used widespread in clinical liver transplantation. Due to a persistent lack of data, we performed this systematic investigation of in situ and ex situ perfusion of liver grafts with HTK (low-viscous) and UW (high-viscous) solutions at different pressure steps on the perfusion solution (gravity flow, 50, 100, 150, and 200 mm Hg). End points were perfusion flow and pressure in the hepatic artery. A pig model was used with n = 8 pigs randomized to each (HTK and UW) group. In situ perfusion was ineffective for both solutions at any pressure on the perfusate bag. Ex situ perfusion showed significantly improved flow and pressure in the hepatic artery and, therefore, was highly effective. No major differences between HTK and UW solutions could be detected. Therefore, an additional ex situ perfusion of the hepatic artery should be mandatory in every liver procurement. PMID- 17351324 TI - Risk factors for functional decline in nonagenarians: a one-year follow-up. The NonaSantfeliu study. AB - BACKGROUND: Disability and a decline in functional capacity are common in old age. OBJECTIVE: To determine predictors of functional decline in nonagenarians' basic activities of daily living (ADL) after 1 year of follow-up. METHODS: A sample of 97 nonagenarians subjects not previously severely dependent (Barthel Index >59) was evaluated. This sample included 72 women (74.2%) and the mean (SD) age was 93.4 +/- 2.7 years. The following data were collected: sociodemographic data, Barthel Index (BI), Lawton-Brody Index (LI), Mental State Examination (MEC), a short version of the Mini-Nutritional Assessment, comorbidity (Charlson Index), lower-extremity function, Gait Rating Scale from the Tinetti Performance Oriented Mobility Scale and prevalent chronic diseases. Subjects who had a 10 point or higher decline in the BI in 1 year were compared to subjects who had no decline or a maximum decline of 9 points. In addition, subjects whose total BI score fell below 60 were compared to the group of subjects who maintained scores between 60 and 100. The Student's t test, the chi(2) or the Fisher's exact test, and a multiple logistic regression analysis (with the identified risk factors of age and gender) were performed. RESULTS: 39 nonagenarians experienced a 10-point or higher decline in the BI in 1 year. A lower LI score (p = 0.003) and visual impairment (p = 0.01) were associated with functional decline. The multiple regression analysis showed that there was a significant association with LI (odds ratio (OR) 0.74, confidence interval 95% 0.60-0.91, p < 0.005). The 18 nonagenarians who had a BI <60 had a BI >60 at baseline. Lower scores on the LI (p = 0.004) and on the MEC (p = 0.01), a history of a previous stroke (p = 0.009) and higher Charlson Index scores (p = 0.03) were associated with recently acquired, severe dependency. A multiple regression analysis showed a significant association between LI (OR 0.65, 0.47-0.89, p < 0.008) and a history of previous strokes (OR 3.39, 1.01-11.34, p < 0.04). CONCLUSIONS: According to the definition used to describe functional basic ADL decline, poor performance in instrumental ADL at baseline and a history of a stroke appear to be independent risk factors. Prevention strategies could be intensified in this subgroup of nonagenarians. PMID- 17351326 TI - Analysis of the relationship between pollinosis and date of birth in Switzerland. AB - BACKGROUND: The first months of life may represent a vulnerable period in the development of atopic diseases. The objective of this study was to examine the relationship between the month of birth and the development of birch and grass pollen allergy in the Swiss population. METHODS: Data from the Swiss Study on Air Pollution and Lung Diseases in Adults(SAPALDIA) as well as the Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution and Climate (SCARPOL) were used. A logistic regression was calculated with grass and birch pollen sensitisation (positive skin prick test) or allergy (positive skin prick test and allergic symptoms) as outcome variables and the season of birth as predictor variable. The contribution of the season of birth on pollinosis was further adjusted for well-known risk factors and potential confounding variables. RESULTS: The logistic regression revealed a significant effect of the season of birth on birch pollen sensitisation and an effect of borderline significance on birch pollen allergy, i.e. subjects born in the pollen season (March to April) showed an increased risk of being sensitised/allergic to birch pollen. The results also indicated a tendency towards an increased risk for subjects born in the grass pollen season (May to June) to develop grass pollen allergy. CONCLUSION: Our results support the hypothesis that the first few months of life constitute a sensitive period, during which inhalative exposure to certain allergens may predispose to the subsequent development of atopic respiratory disease. PMID- 17351327 TI - Allergic sensitization and disease in mother-child pairs from Germany: role of early childhood environment. AB - BACKGROUND: Early childhood influences are important for the development of the allergic phenotype. In East Germany, tremendous lifestyle changes took place after 1990 and it can be hypothesized that the allergic phenotypes in mothers and their children are less similar than in West Germany. This was investigated in our study done in mothers and their 6-year-old children from East and West Germany in the year 2000. METHODS: 1,393 mother-child pairs participated. A subgroup of 774 pairs gave blood for the determination of specific IgE. Regional differences in mother-child correlations and in prevalence of mother-child combinations with respect to allergic sensitization and disease were examined by logistic regression analysis. RESULTS: The adjusted association in positive allergic sensitization between mothers and their children was not significant in East Germany (OR 1.23, 95% CI: 0.68-2.24) but highly significant in West Germany (OR 2.89, 95% CI: 1.73-4.80). The probability for the combination of 'negative' mother and 'positive' child was significantly higher in East than in West Germany. CONCLUSIONS: Mother-child transmission of atopy predisposition can even be cancelled by environmental changes. PMID- 17351325 TI - Animal models for small for gestational age and fetal programming of adult disease. AB - Fetal growth retardation is a fetal adaptation in response to inadequate supply of oxygen and/or nutrients. Animal models of intrauterine growth retardation are an invaluable tool to question the genetic, molecular and cellular events that determine fetal growth and development. Rodent and non-litter bearing animals are mammalian system with similar embryology,anatomy and physiology to humans. Utilization of these systems has led to a greater understanding of the pathophysiology and consequences of intrauterine growth retardation. These observations are comparable to that observed in humans born small for gestational age, and are of interest because of the known association between poor fetal growth and development of adult disease. All the experimental manipulations described here have altered a number of metabolic and physiological variables, but the pattern of alterations seems to vary with the procedure and species employed. This review describes animal models for intrauterine growth retardation and assesses their potentials and limitations at aiming to improve strategies for the prevention of adult disease. PMID- 17351328 TI - C-Reactive protein-induced endothelial microparticle generation in HUVECs is related to BH4-dependent NO formation. AB - BACKGROUND: C-reactive protein (CRP) has been proven to facilitate endothelial injury via reduced NO production. Endothelial microparticles (EMPs) have emerged as a novel marker of endothelial injury. METHODS: In vitro cultured human umbilical vein endothelial cells (HUVECs) were incubated with CRP (20 mg/l) for 24 h. The numbers of EMPs with CD31- and CD51-positive staining were assessed flow-cytometrically, and NO production was measured using the Griess reaction in the presence or absence of tetrahydrobiopterin (BH(4)), respectively. RESULTS: The number of EMPs was significantly increased in HUVECs stimulated by CRP compared with the control group and, in parallel, NO production was decreased (p < 0.05). In the presence of CRP, pretreatment with BH(4) decreased EMP counts and restored NO production to baseline levels (p < 0.05) while pretreatment with 2,4 diamino-6-hydroxypyrimidine (DAHP), a BH(4) synthesis inhibitor, further prompted EMP formation and decreased NO production (p < 0.05). However, adding exogenous BH(4) after pretreatment with DAHP suppressed EMP formation and restored NO production (p < 0.05). CONCLUSIONS: This study demonstrates that CRP induces EMP generation in HUVECs and this effect is, at least in part, related to impaired BH(4)-dependent NO production. Augmented EMP generation in HUVECs is suggested as a novel potential mechanism contributing to the pathogenesis of vascular injury related to CRP. PMID- 17351329 TI - What's your diagnosis: Epidermoid cyst in bone. PMID- 17351330 TI - ER-phagy: selective autophagy of the endoplasmic reticulum. AB - Throughout their life, cells must maintain homeostasis while facing constantly fluctuating demands on their different organelles. A major mechanism for the homeostatic control of organelle function is the unfolded protein response (UPR), a signaling pathway that triggers a comprehensive remodeling of the endoplasmic reticulum (ER) and the biosynthetic pathway according to need. We discovered that activation of the UPR in yeast also induces a new branch of macroautophagy that selectively targets the ER. We term this process "ER-phagy", in analogy to pexophagy and mitophagy, the two other known forms of organelle-specific marcoautophagy. ER-phagy involves the generation of autophagosomes that selectively include ER membranes and whose delimiting double membranes also derive, at least in part, from the ER. This finding provides direct evidence that the ER can serve as a membrane source for autophagosome formation and indicates that ER-phagy entails engulfment of the ER by itself. ER-phagy could remove damaged or redundant parts of the ER and thus represent an important degradative functionality of the UPR that helps to afford homeostatic control. PMID- 17351331 TI - Collaboration of proteolytic systems. PMID- 17351332 TI - Nanoparticles as a novel class of autophagy activators. AB - Nano-sized objects exist as engineered tools as well as natural or anthropogenic environmental factors. Recent progress in the field of nanotechnology allows for a deeper understanding of their impact on organisms. Recently, we showed that the size-dependent cell interaction with quantum dots is autophagy-mediated. The potential role of other endo- and exogenous nanoparticles in terms of autophagy is discussed here. Their physical properties should be taken into consideration while constructing delivery systems. Furthermore, we propose several models of targeted nanoparticles delivery. Autophagy can be considered as an additional mechanism providing intracellular selectivity for introduced nanoparticles. PMID- 17351333 TI - Oxidative stress overrides the spindle checkpoint. AB - Aneuploidy, an abnormal chromosome set, can ensue from failure of the spindle checkpoint, the safeguard mechanism that halts anaphase onset until mitotic spindle assembly. Inefficiency of cells to maintain the normal chromosome set across cell generations has been linked to tumorigenesis and senescence. Here we show that oxidative stress overrides the spindle checkpoint mechanism. Oxidant challenge of checkpoint-arrested cells led to proteolysis of the anaphase inhibitor securin and mitotic cyclins. This appeared consequent to loss of cyclin B-cdk1 activity caused by oxidant-induced reversal of cdk1 inhibitory phosphorylation. These observations may provide a link between aneuploidy occurrence and oxidative stress. PMID- 17351334 TI - Cell division and maintenance of epithelial integrity in the deafened auditory epithelium. AB - Quiescence is among the hallmarks of the sensory epithelium of the cochlea. When auditory sensory cells (hair cells) degenerate they are not replaced, and therefore hearing loss is permanent. Cochlear hair cells are susceptible to several types of lesions, including aminoglycoside antibiotics. The application of the aminoglycoside neomycin in the inner ear mimics cases of severe hair cell loss and leads to collapse of the cochlear epithelium. We now report that in mature guinea pig cochleae injected with neomycin, the remaining nonsensory cells undergo robust proliferative response. p27( Kip1), an inhibitor of cell cycle in the cochlea, was present in nondividing cells and absent during mitosis. Dividing cells retained their tight junction complexes and maintained the structural confluence of the auditory epithelium during cell division. The plane of mitosis was invariably parallel to the luminal surface. These results indicate that the flat epithelium of the cochlea can down-regulate p27( Kip1) and divide after a severe lesion and suggest that the cell divisions assist in maintaining the epithelial confluence throughout the cochlea. Presence of mitosis in the tissue presents therapeutic opportunities for gene transfer and stem cells therapies. PMID- 17351336 TI - XRCC3 depletion induces spontaneous DNA breaks and p53-dependent cell death. AB - In vertebrate cells, Xrcc3 initiates the repair of exogenous induced-DNA breaks during S and G(2)/M phases of the cell cycle by homologous recombination. However, much less is known of the role of Xrcc3 in the response to spontaneous DNA breaks. Using a siRNA approach, we show that depletion of XRCC3 inhibits the proliferation of MCF7 breast cancer cells. This inhibition of replication coincides with the accumulation of DNA breaks, as shown by the comet assay. Cell cycle specific analysis of gammaH2AX expression shows that S and G2/M phase cells express the highest fraction of gammaH2AX positive cells. This is consistent with replication-dependent accumulation of DNA breaks and deficient homologous recombination. While the induction of gammaH2AX is followed by cell death in parental cells, a p53 knockdown derivative becomes more resistant to XRCC3 depletion-induced death without changes in the levels of gammaH2AX. These results show that XRCC3 is required for the proliferation of MCF7 cells, and that decrease in its expression leads to the accumulation of DNA breaks and the induction of p53-dependent cell death. PMID- 17351335 TI - A dominant role for p53-dependent cellular senescence in radiosensitization of human prostate cancer cells. AB - Because p53 inactivation may limit the effectiveness of radiation therapy for localized prostate cancer, it is important to understand how this gene regulates clonogenic survival after an exposure to ionizing radiation. Here, we show that premature cellular senescence is the principal mode of cell death accounting for the radiosensitivity of human prostate cancer cell lines retaining p53 function. Alternative stress response pathways controlled by this tumor suppressor, including cell cycle arrest, DNA damage repair, mitotic catastrophe and apoptosis, contributed significantly less to radiation-induced clonogenic death. Using a dominant negative C-terminal fragment of p53, we present the first evidence that a complete loss of endogenous p53 function is sufficient to limit the irradiation-induced senescence and clonogenic death of prostate cancer cells. Conversely, inheritance of wild-type p53 by prostate cancer cells lacking a functional allele of this gene (i.e., DU145) significantly increases clonogenic death through p53-dependent cellular senescence and apoptotic pathways. Our data provide evidence that mutations of even one p53 allele may be sufficient to alter their clonogenic fate. In addition, they support the idea that the p53 pathway can be used as a specific target for enhancing the radiosensitivity of prostate cancer cells. Activation of p53 by the drug nutlin-3 is shown to be an effective radiosensitizer of prostate cancer cells retaining functional alleles of p53 and this effect was entirely attributable to an increased induction of p53-dependent cellular senescence. PMID- 17351337 TI - Interfering with MAP kinase docking interactions: implications and perspective for the p38 route. AB - Docking interactions are key to understand the dynamic assembly of signal transduction complexes in the cell. In particular, the docking domain (D domain) dependent interactions described so far for several MAPK routes are essential to specify the upstream regulators, downstream mediators and also inactivators that complex with the p38, JNK and ERK proteins. In addition to contributing to the maintenance of the linearity and specificity of these pathways, novel data have revealed that docking contacts also regulate the activity, subcellular distribution and substrate selection of each MAPK. Moreover, phosphorylation inside or around a docking domain is emerging as a novel mechanism of regulation of MAPK association with cellular partners, suggesting new potential strategies for the design of selective MAPK inhibitors. Here, we discuss these novel data and the biochemical and cellular implications they may have with specific emphasis on the p38 route. PMID- 17351338 TI - Inhibitor of NF kappa B alpha is a host sensor of coxsackievirus infection. AB - Apoptosis is a host response to viral infection: programmed cell death can limit viral replication. Therefore, the knowledge of pathways by which cells detect viral infection and activate apoptosis may be of considerable interest when developing strategies against viral pathogens. We have shown that cells activate apoptosis in response to Coxsackievirus B3 (CVB3) infection. In an effort to discover how cells detect viral infections, we found that the viral protease 3C(pro) cleaves IkappaBalpha. Truncated IkappaBalpha forms a stable complex with NFkappaB, translocates to the nucleus and inhibits NFkappaB transactivation, increasing apoptosis and decreasing viral replication. In contrast, cells in which IkappaBalpha expression is reduced are more susceptible to viral infection, showing less apoptosis and more viral replication. IkBalpha thus acts as a sensor of viral infection. Cleavage of host proteins by pathogen proteases is a novel mechanism by which the host recognizes and responds to viral infection. PMID- 17351339 TI - Inhibition of VEGF signaling pathways in multiple myeloma and other malignancies. AB - Due to its direct effects on endothelial cells, circulatory endothelial progenitor cells, hematopoietic stem cells, immune cells, osteoclasts, osteoblasts and neurons, vascular endothelial growth factor (VEGF) is linked to tumor cell development, progression, metastatic osteolysis and drug resistance, as well as clinical features such as metastatic osteolysis. Importantly, recent advances in the understanding of mechanisms of action of antiangiogenic drugs/VEGF-inhibitors have fundamentally changed treatment regimens in cancer. VEGF plays a key role not only in solid tumors but also in hematologic malignancies, including multiple myeloma (MM). Despite recent advances in our understanding of MM pathogenesis and novel therapies (bortezomib and lenalidomide), it remains incurable. Our own and others' work suggest that VEGF inhibitors e.g., the small molecule VEGF receptor inhibitor pazopanib, may also improve patient outcome in MM. PMID- 17351340 TI - Glycogen synthase kinase-3 phosphorylates and regulates the stability of p27kip1 protein. AB - p27Kip1 is a critical regulator of the eukaryotic cell cycle. It acts as a check point protein and regulates cell cycle progression at the G1 and G1/S phase as well as predominantly blocks cell cycle progression in the absence of growth factors. Intracellular turnover of p27 is tightly regulated at the level of translation as well as by posttranslational modification. The mechanism by which p27 protein is rapidly degraded during the G1 and G1/S phase transition is well characterized. However, the process by which p27 remains extremely stable in the absence of growth factors remains unknown. Here, we report that GSK-3 dependent phosphorylation of p27 protein is essential for its enhanced stability. p27 protein harbours 2 functional GSK-3 phosphorylation sites at the C- terminus, which was found to be effectively phosphorylated by the cognate enzyme both in vitro and in vivo. Combined with earlier observation which shows that it phosphorylates and triggers cyclin D degradation; GSK-3 now appears to be a central mediator of the cell-cycle regulatory network, where it acts as a two-way switch, phosphorylating and targeting pro-proliferative factors for degradation on one hand and simultaneously phosphorylating and stabilizing an anti proliferative factor on the other hand. This dual mode of activity may doubly ensure that cell cycle progression is aptly prohibited under conditions of limited growth factor availability. PMID- 17351342 TI - Oncogenes in myeloproliferative disorders. AB - Myeloproliferative disorders (MPDs) constitute a group of hematopoietic malignancies that feature enhanced proliferation and survival of one or more myeloid lineage cells. William Dameshek is credited for introducing the term "MPDs" in 1951 when he used it to group chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) under one clinicopathologic category. Since then, other myeloid neoplasms have been added to the MPD member list: chronic neutrophilic (CNL), eosinophilic (CEL) and myelomonocytic (CMML) leukemias; juvenile myelomonocytic leukemia (JMML); hypereosinophilic syndrome (HES); systemic mastocytosis (SM); and others. Collectively, MPDs are stem cell-derived clonal proliferative diseases whose shared and diverse phenotypic characteristics can be attributed to dysregulated signal transduction--a consequence of acquired somatic mutations. The most recognized among the latter is BCR-ABL, the disease-causing mutation in CML. Other mutations of putative pathogenetic relevance in MPDs include: JAK2V617F in PV, ET, and PMF; JAK2 exon 12 mutations in PV; MPLW515L/K in PMF and ET; KITD816V in SM; FIP1L1-PDGFRA in CEL-SM; rearrangements of PDGFRB in CEL-CMML and FGFR1 in stem cell leukemia-lymphoma syndrome; and RAS/PTPN11/NF1 mutations in JMML. This increasing repertoire of mutant molecules has streamlined translational research and molecularly targeted drug development in MPDs. PMID- 17351341 TI - Role of the CDKN1A/p21, CDKN1C/p57, and CDKN2A/p16 genes in the risk of atherosclerosis and myocardial infarction. AB - Atherosclerosis is characterized by excessive proliferation of neointimal leukocytes and vascular smooth muscle cells (VSMCs). In mice, the manipulation of cell cycle inhibitors such as CDKN1B (p27) and CDKN1A (p21) modifies the risk of developing atherosclerosis. In humans, CDKN1A, CDKN1B and CDKN1C (p57) are differentially expressed in normal versus atherosclerotic vessels. A DNA polymorphism within the CDKN1B promoter has been associated with myocardial infarction (MI). In the present study, we analyzed the effect of CDKN1A, CDKN1C and CDKN2A (p16) polymorphisms on MI-risk. A total of 316 patients (all male, < 55 years) and 434 controls were genotyped, and the allele and genotype frequencies were compared between the two groups. Two CDKN1C polymorphisms, a promoter GT-repeat and a variable number of repeats of the amino acid PAPA-motif, were associated with MI. The presence of two alleles < or = 11-repeats (9/11, 10/11 and 11/11 genotypes) was significantly less frequent among patients (p < 0.001). This difference was also significant when analyzing the subpopulation of smokers (p = 0.004), suggesting a protective role for these low-repeat genotypes (OR = 0.49, 95%CI = 0.32-0.73). The PAPA-BB homozygotes were significantly less frequent in patients, but this could be attributed to a linkage disequilibrium between the 11-repeats and B alleles. No significantly different frequencies between patients and controls for the four CDKN1A (-1026A/G, -754G/C, -369G/C and Ser31Arg) and the three CDKN2A (-523 G/A, +22 G/A and Ala148Thr) polymorphisms was found. In conclusion, we provide here genetic evidence for the association between DNA-variants in the CDKN1C/p57 gene and the risk of atherosclerosis and MI. PMID- 17351343 TI - Mig-6, signal transduction, stress response and cancer. AB - The mitogen-inducible gene-6 (Mig-6) is an immediate early response gene encoding a nonkinase scaffolding adaptor protein. Mig-6 gene expression can be rapidly and robustly induced under both normal and pathological scenarios by factors including hormones, growth factors, and stresses. However, the precise role of Mig-6 has virtually been a mystery until recently, when we and others discovered that Mig-6 may play important roles in regulating stress response, maintaining homeostasis in tissues like joints or cardiac muscle, and functioning as a tumor suppressor. The discovery that Mig-6 acts as a negative feedback inhibitor of EGF receptor signaling through a direct, physical interaction with the EGF receptor opens a door for understanding the mechanism underlying Mig-6 function. Yet how Mig-6 fine tunes or integrates signal transduction in many pathophysiological situations remains to be determined. Here we will highlight recent discoveries on the role of Mig-6 in stress response, tissue homeostasis, and cancer development; review the transcriptional regulation of Mig-6 expression; share insight into its mechanism in regulating signal transduction; and discuss the paradox of its action modes under different pathophysiological conditions. PMID- 17351345 TI - Inactivated poliovirus vaccine. PMID- 17351344 TI - p38 MAP kinase regulates stem cell apoptosis in human hematopoietic failure. AB - Myelodysplastic syndromes (MDS) are clonal stem cell disorders that lead to ineffective hematopoiesis and are common causes of low blood counts in the elderly. The exact molecular mechanisms regulating increased stem apoptosis in these disorders are not well defined. p38 MAPK activation is important in regulating the growth inhibitory signals of TNF-alpha, TGF-beta and Interferons on human hematopoiesis. Our findings show that p38 MAPK is overactivated in myelodysplasia bone marrows and regulates hematopoietic stem cell apoptosis. Inhibition of p38 MAPK by genetic or pharmacologic means decreases apoptosis and stimulates in vitro hematopoiesis from primary MDS hematopoietic progenitors. These studies point to the potential efficacy of selective p38alpha inhibitor, SCIO-469, in human bone marrow failure. PMID- 17351346 TI - G2 checkpoint kinase inhibitors exert their radiosensitizing effects prior to the G2/M transition. AB - Chemical inhibitors of the G2 checkpoint can sensitize p53-defective cancer cells to DNA damage and several are in preclinical or clinical development. These compounds are commonly thought to increase killing at the G2/M transition by forcing cells to divide with unrepaired DNA. We examined the effects of the ATM/ATR inhibitor caffeine and the Chk1 inhibitor isogranulatimide on the clonogenic survival of two p53-defective cell lines, MCF7-mp53 and HCT-116 p53-/- cells, when added at different times after exposure to ionizing radiation. Exposure 16-24 h after irradiation, when G2 arrest is maximal, forced premature entry into mitosis but increased clonogenic survival. Radiosensitization occurred mostly upon exposure between 2 and 16 h after irradiation, correlating with S phase traversal. These results suggest that inhibition of the S phase activities of ATM/ATR and Chk1 may be more relevant to radiosensitization of p53-defective cells than G2 checkpoint abrogation and that careful scheduling of combination treatments might be required for synergistic antitumour effects in vivo. PMID- 17351347 TI - Severe mental retardation, epilepsy, anal anomalies, and distal phalangeal hypoplasia in siblings. AB - We report two sisters born to consanguineous parents with an identical syndrome consisting of severe mental retardation and epilepsy, hypoplastic terminal phalanges, and anteriorly displaced anus. Further metabolic and genetic testing failed to detect the etiology. A whole genome linkage scan showed homozygosity for a 28-Mb region on chromosome 1p, and a 65-Mb region spanning most of chromosome 14. These results are consistent with an autosomal recessive condition that is similar to, but likely distinct from, Coffin-Siris syndrome. PMID- 17351348 TI - Evaluating the association between congenital cystic adenomatoid malformation of the lung and abdominal wall laxity. AB - We report a male fetus with congenital cystic adenomatoid malformation of the lung, who was treated by laser with resolution of hydrops. Postnatally, the infant had the typical abdominal wall laxity and undescended testes characteristic of prune-belly syndrome. The sonographic diagnosis of cystic adenomatoid malformation was confirmed histologically after postnatal resection. The relationship between cystic adenomatoid malformation and prune-belly syndrome is evaluated through analysis of the present and previously reported cases. We show that there does appear to be a true association between cystic adenomatoid malformation and prune-belly syndrome. We also, however, demonstrate that the traditional explanation (cystic adenomatoid malformation-related hydrops causes ascitic abdominal distension resulting in prune-belly syndrome) is unlikely to be straightforwardly correct. PMID- 17351349 TI - Two cases of macrocephaly and immune deficiency. AB - Macrocephaly describes a head circumference greater than two standard deviations above the mean and is a feature of a number of genetic syndromes. Here we report on two patients with microcephaly, immune deficiency and anemia. In addition, one case had periventricular leukomalacia and the other case had myelinisation delay in periventricular white matter development. These cases may represent a distinct new syndrome. PMID- 17351350 TI - New clinical findings in the Richieri-Costa/Pereira type of acrofacial dysostosis. AB - The Richieri-Costa/Pereira form of acrofacial dysostosis is an autosomal recessive condition characterized by short stature, Pierre-Robin sequence, preaxial and postaxial abnormalities in hands, congenital talipes, cleft mandible and malformations of the larynx. We report female infant presenting with severe micrognathia, a hypoplasic clavicle, median mandible cleft, bilateral hand abnormalities and talipes, laryngeal malformations, hip subluxation with acetabular dysplasia and mesomelic shortening of limbs. A few reported patients have clavicular hyploplasia but hip subluxation with acetabular dysplasia and mesomelic shortening of limbs have not been described. PMID- 17351351 TI - Warburg Micro syndrome in a Turkish boy. AB - We report a 4-year-old Turkish boy with Warburg Micro syndrome born to consanguineous parents. He had ptosis, deep-set eyes, microphthalmia, microcornea, microcephaly, prominent ears and nasal root, micrognathia, hypertrichosis, spastic diplegia, skin hyperextensibility and joint hypermobility, hypogenitalism, cerebral atrophy and hypoplasia of corpus callosum and cerebellum. Sequence analysis of exon 8 of the RAB3GAP gene has confirmed the presence of a splice donor mutation (748+1G>A) in the homozygous state. Skin hyperextensibility and joint hypermobility in the affected child have not been reported in Warburg Micro syndrome cases to date. This report compares the symptoms and features of the case with previously reported cases of Warburg Micro syndrome. PMID- 17351352 TI - Torg-Winchester syndrome: lack of efficacy of pamidronate therapy. AB - Torg-Winchester syndrome, which includes nodular arthropathy with osteolysis (OMIM 605156), is a condition associated with generalized osteoporosis. On the basis of usefulness of pamidronate in conditions with osteoporosis, we hypothesized that the drug will improve osteolysis and/or osteoporosis in this condition. After obtaining informed consent from the parents, two siblings affected with Torg-Winchester syndrome were administered intravenous pamidronate over a period of 3 years. The clinical status was monitored along with the bone mineral density (using radiographs and X-ray densitometry) to assess the effect of the drug. Clinically there was no improvement. Although the bone mineral density improved in axial skeleton, osteoporosis and osteolysis continued to worsen in the appendicular skeleton. We conclude that pamidronate does not improve peripheral osteolysis in multicentric osteolysis and nodular arthropathy caused by mutation in matrix metalloproteinase 2 gene. PMID- 17351353 TI - Relatively mild phenotype in a patient with interstitial 6q24.3-q25.2 deletion. AB - We report a patient with a de-novo interstitial deletion of chromosome 6 with breakpoints at q24.3-q25.2. The patient presented with intra-abdominal testes, mild dysmorphic features, feeding difficulties in the first 3 years of life and normal development with no learning difficulties. To our knowledge this is the first report of a 6q interstitial deletion with these particular breakpoints. This is also the first patient with an interstitial 6q deletion and normal intellectual development. Cryptorchidism seems to be a recurrent finding in males with 6q deletions involving similar breakpoints. PMID- 17351354 TI - Hypotonia, developmental delay and features of scalp-ear-nipple syndrome in an inbred Arab family. AB - We report two children from an inbred Arab family with features suggestive of scalp-ear-nipple syndrome who in addition had severe hypotonia and developmental delay. Also addition, other features seen in scalp-ear-nipple syndrome such as camptodactyly, syndactyly and dry skin were absent in these children. We suggest the children in this report have a severe recessive form of this syndrome. PMID- 17351355 TI - Interstitial deletion of the short arm of chromosome 1 (1p13.1p21.1) in a girl with mental retardation, short stature and colobomata. AB - Interstitial deletions on the short arm of chromosome 1 are rare. We describe a girl with severe mental retardation, short stature and dysmorphic features including colobomata where high-resolution comparative genomic hybridization revealed an interstitial deletion with breakpoints in band 1p13.1 and 1p21.1. The deletion was further characterized by real-time polymerase chain reaction. We hypothesize that haploinsufficiency of WNT2B (wingless-type MMTV integration site family, member 2B) and NTNG1 (Netrin G1) contributed to the patient's phenotype. PMID- 17351356 TI - Nasopharyngeal teratoma associated with a complex congenital cardiac anomaly. PMID- 17351357 TI - Duplication of the nipples and areolae. AB - A young South African woman has bilateral duplication of the nipples and areolae in an apparently horizontal plane on each breast. She is otherwise normal in every respect, and her family history is negative. This configuration of breast tissue is very unusual and, to the best of our knowledge, it has not previously been reported. PMID- 17351358 TI - Osteocraniostenosis: a further case report documenting the antenatal findings. AB - Osteocraniostenosis is a rare, lethal skeletal dysplasia with a distinctive phenotype and diagnostic X-ray findings. We present a case of an infant who was antenatally detected to have dysmorphic facial features as early as 22 weeks of gestation. Subsequent postnatal investigations confirmed the diagnosis of osteocraniostenosis. These antenatal findings have not been documented previously. We discuss both the antenatal and postnatal findings of this condition. PMID- 17351359 TI - Cerebro-facio-thoracic dysplasia: expanding the phenotype. AB - We report a further two patients with cerebro-facio-thoracic dysplasia, a rare autosomal recessive condition with thoracic costovertebral dysplasia, developmental delay and characteristic facial features. One of our patients has the additional features of large, bilateral colobomas of the optic nerve, ptosis, small conical teeth and severe left-sided talipes. He also has hypermobile joints, especially in his hands and anterior subluxation of the shoulders. The second patient has hypodensity of the grey matter on magnetic resonance imaging, which is the second report of this finding in cerebro-facio-thoracic dysplasia. In addition, he has hypoplasia of the corpus callosum. These cases illustrate the expanding phenotype of this condition, and support the hypothesis that this is an autosomal recessive condition. PMID- 17351360 TI - Prader-Willi and Klinefelter syndrome: a coincidence or not? AB - Prader-Willi syndrome is a complex multisystem disorder characterized by neonatal hypotonia, developmental delay, short stature, obesity, behaviour problems, hypothalamic hypogonadism and characteristic appearance. A number of sex chromosome abnormalities have been reported in children with Prader-Willi syndrome. We report on an infant with a 47, XXY karyotype and Prader-Willi syndrome diagnosed at 2 months of age. He is possibly the youngest to be reported with both Prader-Willi syndrome and Klinefelter syndrome. We have shown that the extra X chromosome causing Klinefelter syndrome is paternal in origin and Prader Willi syndrome is due to maternal heterodisomy indicating that these two events occurred coincidentally. PMID- 17351361 TI - Encephalomyopathy and optic atrophy with tall stature and mitochondrial dysfunction: a new syndrome. PMID- 17351362 TI - Antioxidant activity of carvedilol in cardiovascular disease. AB - Oxidative and inflammatory stresses are cardinal in the pathogenesis of hypertension and atherosclerosis. Oxidative stress also leads to the induction of inflammation through the activation of proinflammatory transcription factors. Understanding the mechanisms leading to oxidative stress and the means of suppressing it are important in controlling complications related to atherogenesis, since oxidative and inflammatory stress are important in the pathogenesis of atherosclerosis. The failure of chemical antioxidants [which scavenge reactive oxygen species (ROS)], such as vitamins E and C, has led to further exploration of the ROS-suppressive effects of drugs used in the treatment of cardiovascular disease. Carvedilol has been shown to possess both ROS scavenging and ROS-suppressive effects, and its use is associated with a reduction in oxidative stress. Furthermore, anti-inflammatory effects of carvedilol have now been described. Although further clinical investigations are required, these properties may contribute to the improvement in clinical outcomes observed with carvedilol. PMID- 17351363 TI - Blood pressure lowering in acute ischaemic stroke: an update on the role of angiotensin receptor blockers. PMID- 17351364 TI - Aldosterone antagonist therapy in resistant hypertension. PMID- 17351365 TI - How to assess mean blood pressure properly at the brachial artery level. AB - OBJECTIVES: Mean arterial pressure at the upper arm is traditionally calculated by adding one-third of the pulse pressure to the diastolic pressure. We questioned the general validity of this formula. METHODS: We used previously recorded resting intrabrachial pressure and Riva-Rocci Korotkoff blood pressure measurements in 57 subjects (study A) and 24-h intra-arterial recordings obtained in 22 ambulant subjects (study B). RESULTS: In study A the intra-arterially measured 'real' mean pressure was found at 39.5 +/- 2.5% of pulse pressure above diastolic pressure, namely at a level higher than the expected 33.3% of pulse pressure, in all individuals. Results were not related to age, blood pressure, pulse pressure or heart rate levels. Mean pressure calculated with the traditional one-third rule therefore underestimated 'real' mean pressure by 5.0 +/- 2.3 mmHg (P < 0.01) when calculated from intra-arterial pressure readings, and by 4.9 +/- 5.3 mmHg (P < 0.01) when calculated from Riva-Rocci Korotkoff readings. In study B we showed activity-related variations in the relative level of the 'real' mean pressure, which increased by 1.8 +/- 1.4% (P < 0.01) during sleep, and decreased by 0.5 +/- 0.9% during walking (P < 0.05) and by 0.8 +/- 1.3% during cycling (P < 0.01). CONCLUSION: The mean pressure at the upper arm is underestimated when calculated using the traditional formula of adding one-third of the pulse pressure to the diastolic pressure. This underestimation can be avoided by adding 40% of pulse pressure to the diastolic pressure. The proposed approach needs to be validated through larger scale studies. PMID- 17351366 TI - Cardiovascular risk assessment in hypertensive patients: major discrepancy according to ESH and SCORE strategies. AB - BACKGROUND: The European Society of Hypertension (ESH) guidelines recommend two possible strategies for the assessment of cardiovascular risk (CVR) in essential hypertensive (HT) patients: categorical tables and SCORE risk charts. However, the outcome of these methods has not been compared. OBJECTIVE AND METHODS: We assessed CVR according to ESH and SCORE risk charts adapted to use in Belgium in 106 HT patients (mean age: 52.4 +/- 12.9 years, male/female ratio: 46/60) without diabetes or other associated clinical conditions. RESULTS: The distribution of low, moderate, high and very high added risk was strikingly different (kappa coefficient = 0.08) according to ESH categorical tables (n = 1, 24, 24, 57) and SCORE risk charts (n = 60, 12, 10, 24). Furthermore, compared with ESH, CVR class according to SCORE was lower in the majority of patients (n = 72, 68%) while it was similar in 23 (22%) and higher in 11 patients (10%). Patients for whom risk was lower by SCORE compared to ESH differed from the others by age (46.7 +/- 10.0 versus 64.6 +/- 9.2, P < 10) and proportion of females (71 versus 26%, P < 10). CONCLUSIONS: In this series of patients with mainly moderate or severe hypertension, the distribution of cardiovascular risk was strikingly different according to ESH categorical tables and SCORE risk charts. This might be explained in part by the lower weight attributed to blood pressure in risk assessment, especially in young female subjects. If confirmed, these results should prompt the performance of a prospective study to assess which strategy most accurately predicts CVR in hypertensive patients. PMID- 17351367 TI - Effect of the alpha2C-adrenoreceptor deletion322-325 variant on sympathetic activity and cardiovascular measures in healthy subjects. AB - BACKGROUND: The alpha2C-adrenergic receptor plays an important role in the regulation of the sympathetic nervous system and, therefore, blood pressure and heart rate. A deletion polymorphism in its gene (ADRA2C del322-325), ten times more common in black than white Americans, has been associated with a loss of function in vitro and, under controlled study conditions, raised blood pressure and catecholamine secretion. We therefore examined the hypothesis that the ADRA2C deletion variant would alter sympathetic activity and contribute to ethnic differences in blood pressure. METHODS: We measured resting plasma norepinephrine and epinephrine concentrations, blood pressure and heart rate in 224 healthy subjects (127 whites), and determined their ADRA2C del322-325 genotype. Additionally, we analyzed heart rate variability (HRV) in a subgroup of 50 black subjects. RESULTS: Systolic (SBP) and diastolic blood pressure (DBP) were higher in blacks than whites [difference (95% confidence interval), 4.4 (1.5-7.4) mmHg, P = 0.003; and 2.7 (0.7-4.6) mmHg, P = 0.01, respectively]. Norepinephrine concentrations did not differ among subjects with 0, 1 and 2 copies of the deletion variant [median (interquartile range), 185.0 (147.5-269.8), 200.0 (154.9 257.0) and 173.8 (158.5-235.8) pg/ml, respectively; P = 0.54]. Similarly, none of the HRV parameters differed among the genotype groups. In multiple linear regression analyses adjusting for multiple covariates, the deletion genotype was not associated with SBP or DBP. In contrast, black ethnicity was associated with higher SBP (P = 0.001) and DBP (P = 0.005). CONCLUSION: The ADRA2C deletion polymorphism had no effect on markers of resting sympathetic activity and cardiovascular measures, and did not account for ethnic differences in blood pressure. PMID- 17351368 TI - Is the plasminogen activator inhibitor-1 gene a candidate gene predisposing to hypertension? Results from a population-based study in Spain. AB - BACKGROUND: Studies in humans and mice suggest that plasminogen activator inhibitor-1 (PAI-1) might be a candidate gene for arterial hypertension. Our aims were to analyse whether the functional 4G/5G PAI-1 polymorphism represents a risk marker for the development of arterial hypertension regardless of hypertension related metabolic variables. METHODS: Eight hundred and fifteen unrelated individuals (387 men, age 35-74 years) from a cross-sectional, population-based, epidemiological survey in the province of Segovia (Spain) were studied. Anthropometric/biochemical parameters--body mass index, waist circumference, diastolic and systolic blood pressures, high-density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, fasting glucose, insulin, C reactive protein, and PAI-1 levels--were analysed. The 4G/5G PAI-1 genotypes were established by restriction fragment length polymorphism. Insulin resistance was estimated by the homeostasis model assessment. Tobacco consumption data were obtained using a standard questionnaire. RESULTS: The 4G/4G PAI-1 genotype was significantly associated with a high prevalence of arterial hypertension. This association remained statistically significant even after adjustment for hypertension-related metabolic variables in our population (adjusted odds ratio, 1.858; 95% confidence interval, 1.135-3.018; P = 0.013). CONCLUSION: Our results show that the 4G/4G PAI-1 genotype appears to be associated with an elevated relative risk of developing arterial hypertension, regardless of PAI-1 levels and other hypertension-related factors, in a representative sample of the Spanish population. PMID- 17351369 TI - Interaction between the angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea as a mechanism for hypertension. AB - OBJECTIVE: Obstructive sleep apnoea (OSA) confers a risk of hypertension and cardiovascular complications. Both the renin-angiotensin-aldosterone system and OSA are important determinants of blood pressure, but it is not fully known how they interact. The aim of this study was to explore the interaction between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and OSA in the association with hypertension. DESIGN: A community-based, case control design with hypertensive patients in primary care (n = 157) and normotensive population controls (n = 181). METHODS: All subjects underwent ambulatory polysomnography during one night. OSA was defined by a minimum of 10 apnoea/hypopnoea events per hour. Office blood pressure was measured and hypertension status was assessed. The genotypes were determined using polymerase chain reaction. RESULTS: An interaction analysis including sex, ACE I/D polymorphism (DD and ID versus II), and OSA identified a significant interaction between OSA and the ACE I/D polymorphism: odds ratio (OR) 6.3, 95% confidence interval (CI) 1.8-22.5, P = 0.004 as well as between OSA and sex: OR 3.3, 95% CI 1.1-9.6, P = 0.033. OSA was significantly associated with hypertension in men but not in women. CONCLUSION: The interaction between the ACE gene I/D polymorphism and OSA appears to be an important mechanism in the development of hypertension, particularly in men. PMID- 17351370 TI - Effect of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension. AB - OBJECTIVE: It has been shown that angiotensin-converting enzyme inhibition or angiotensin receptor blockade may improve endothelial dysfunction, an early manifestation of atherosclerosis, in patients with diabetes. Whether this protective effect is mediated through blood pressure-lowering effects or other specific mechanisms such as a reduction in oxidative stress is not clear. We investigated the influence of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension. METHODS: Thirteen patients were included in this randomized, double-blind, crossover study; they received losartan 50 mg twice daily for 4 weeks followed by atenolol 50 mg twice daily or vice versa. Concomitant medication with renin angiotensin blocking agents or beta-blockers was withdrawn, whereas other medication remained unchanged. At baseline and after each treatment period, flow mediated dilation of the brachial artery and oxidative stress were measured in serum samples. RESULTS: Flow-mediated dilation was increased significantly after 4 weeks' treatment with losartan (3.4 +/- 0.44%) compared with atenolol (2.58 +/- 0.42%; P = 0.01). 8-Isoprostanes, a marker of oxidative stress, were significantly reduced in the losartan group compared with baseline (0.039 +/- 0.007 versus 0.067 +/- 0.006 ng/ml; P = 0.01), but did not differ from baseline with atenolol. Glucose, hemoglobin A1c, highly sensitive C-reactive protein, lipids and systolic blood pressure remained unaltered, whereas diastolic blood pressure tended to be lower in the atenolol group. CONCLUSIONS: This study demonstrates that losartan significantly improved endothelial function in type 2 diabetes patients with hypertension compared with atenolol. This must be independent of the blood pressure-lowering effect of losartan and is probably caused by an antioxidative effect of the angiotensin receptor blocker. PMID- 17351371 TI - Effects of prostaglandin E1alpha cyclodextrin [corrected] treatment on endothelial dysfunction in patients with systemic sclerosis. AB - OBJECTIVE: Systemic sclerosis (SSc) is characterized by an altered nitric oxide (NO): endothelin I ratio and by endothelial dysfunction. AIMS: To verify the effects of prostaglandin E1 (PGE1) alpha-cyclodestrin treatment on endothelial function, quantified as flow-mediated dilation (FMD) of the radial artery. METHODS: In 16 women with SSc (age 57 +/- 2.7 years, means +/- SE) in whom a diagnosis of SSc had been made several years earlier (7.1 +/- 1.2 years), FMD was evaluated by an echotracking technique on the radial artery, using trinitroglycerin vasodilation as a non-endothelial measure of the vessel's ability to increase its diameter maximally. FMD was evaluated after 4 months washout period and after 4 months cyclic infusion of PGE1 alpha-cyclodestrin. Expired NO was measured at the same time. RESULTS: PGE1 alpha-cyclodestrin cyclic infusions did not modify systolic and diastolic blood pressure, heart rate or trinitroglycerin radial artery vasodilation. On the other hand, it induced a marked and significant increase in FMD of the radial artery, which was also accompanied by an increase in blood flow and expired NO. CONCLUSIONS: Endothelial dysfunction and reduced FMD associated with SSc are improved by cyclic treatment with PGE1 alpha-cyclodestrin. This effect occurs together with a concomitant increase in expired NO, suggesting its direct positive influence on endothelial function. It may also partly explain the clinical beneficial effect of the drug in SSc. PMID- 17351372 TI - Increased store-operated and 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx in monocytes is mediated by transient receptor potential canonical channels in human essential hypertension. AB - OBJECTIVE: Activation of nonselective cation channels of the transient receptor potential canonical (TRPC) family has been associated with hypertension. Whether store-operated channels, which are activated after depletion of intracellular stores, or second-messenger-operated channels, which are activated by 1-oleoyl-2 acetyl-sn-glycerol, are affected in essential hypertension is presently unknown. METHODS: Using a polymerase chain reaction, an in-cell western assay and the fluorescent dye technique we studied TRPC3, TRPC5, and TRPC6 expression and store operated and 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx into human monocytes in 19 patients with essential hypertension and in 17 age-matched and sex-matched normotensive control individuals. RESULTS: We observed a significantly increased expression of TRPC3 and TRPC5, but not TRPC6, in essential hypertension. Store-operated calcium influx was significantly elevated in essential hypertension. Store-operated calcium influx was reduced by the inhibitor 2-aminoethoxydiphenylborane, specific TRPC3 and TRPC5 knockdown, but not TRPC6 knockdown using gene silencing by RNA interference. 1-Oleoyl-2-acetyl sn-glycerol-induced calcium influx and barium influx were also significantly elevated in essential hypertension. The 1-oleoyl-2-acetyl-sn-glycerol-induced cation influx was reduced by TRPC3 and TRPC5 knockdown. CONCLUSION: We demonstrated an increased TRPC3 and TRPC5 expression and a subsequently increased store-operated calcium influx and increased 1-oleoyl-2-acetyl-sn-glycerol-induced cation influx in monocytes of patients with essential hypertension. This increased activation of monocytes through TRPC channels in patients with essential hypertension may promote vascular disease in these patients. PMID- 17351373 TI - Enhancement of receptor-operated cation current and TRPC6 expression in arterial smooth muscle cells of deoxycorticosterone acetate-salt hypertensive rats. AB - OBJECTIVES: In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, altered reactivity of blood vessels to vasoactive agonists is frequently associated with an elevation in blood pressure. Canonical transient receptor potential (TRPC) channels are believed to encode receptor-operated cation channels (ROC), the activation of which is involved in smooth muscle depolarization and vasoconstriction. The aims of the present study were to investigate whether the ROC current is increased in DOCA-hypertensive rats and determine whether aldosterone directly enhances the expression of TRPC. METHODS: The nystatin perforated patch-clamp technique was used for the recording of receptor stimulated ion currents in mesenteric arterial smooth muscle cells, which were enzymatically dispersed from sham-operated and DOCA-salt hypertensive rats. Expressions of TRPCs were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and by Western blot analysis. RESULTS: Receptor-stimulated currents activated by 5-hydroxytryptamine (serotonin) and norepinephrine were increased significantly in the mesenteric arterial smooth muscle cells of DOCA salt hypertensive rats compared to sham-operated rats. Ion-substitution experiments revealed that the enhanced currents were cation currents (ROC currents). Enhanced expression of TRPC6 in mesenteric arteries from DOCA-salt hypertensive rats was demonstrated by real-time RT-PCR. Up-regulation of TRPC6 by aldosterone treatment in vitro was also observed in A7r5 cells by RT-PCR and in western blots. CONCLUSION: These results suggest that aldosterone enhances TRPC6 expression and ROC currents in vascular smooth muscle cells, and that this may in turn contribute to altered vascular reactivity and to hypertension. PMID- 17351374 TI - Augmentation index and carotid intima-media thickness are differently related to age, C-reactive protein and oxidized low-density lipoprotein. AB - OBJECTIVE: Ageing, plasma circulating C-reactive protein (CRP), oxidized low density lipoprotein (OxLDL) and homocysteine (Hcy) are associated with atherosclerosis. The aim of this study was to evaluate the relationship between age, inflammatory and oxidative stress-related markers with functional and structural changes of the arteries in asymptomatic persons. METHODS: CRP, OxLDL and Hcy were measured in 175 clinically healthy subjects, aged 40-70 years. Ultrasonography and pulse wave analysis were used to measure carotid intima-media thickness (IMT) and augmentation index (AIx). RESULTS: OxLDL was correlated with IMT (r = 0.24, P = 0.003), whereas CRP was correlated with AIx (r = 0.21, P = 0.005). No correlation was detected between Hcy and AIx or age-adjusted IMT. There was a significant association between AIx and age 50 years (r = 0.40; P = 0.001). In stepwise regression analysis age, weight, white blood cell count, OxLDL, heart rate and timing of the reflected waveform adjusted for height were significantly and independently associated with IMT (R = 0.41; P < 0.001). At the same time, AIx as the dependent variable correlated positively with age, gender, CRP and mean arterial pressure, and negatively with heart rate, weight and height, in stepwise regression analysis (R = 0.63; P < 0.001). CONCLUSION: The results of the present study showed that CRP, OxLDL, Hcy and age are not similarly related to AIx and IMT in asymptomatic persons. The results suggest that CRP and younger age are related to arterial stiffness, whereas OxLDL and older age become more important determinants of structural changes of the arteries in asymptomatic persons. PMID- 17351375 TI - Estimate of white-coat effect and arterial stiffness. AB - OBJECTIVES: Blood pressure (BP) measured in the office is usually higher than the average ambulatory BP, a difference generally taken as an estimate of the white coat effect. This study was designed to assess whether such a difference is associated with impairment of the conduit arterial system. METHODS: We calculated the difference between office and average daytime peak systolic blood pressure (DeltaSBP) in 2778 hypertensive participants (1240 women) of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale cohort. Arterial stiffness was evaluated using an adjusted office pulse pressure to stroke volume ratio (PP/SV), measured at rest, which has previously been shown to predict cardiovascular outcome independent of echocardiographic left ventricular hypertrophy. Effective arterial elastance was also estimated. RESULTS: Across quintiles of PP/SV, significant linear, positive trends were found with age, the proportion of women, plasma glucose and triglyceride levels (0.05 > P < 0.0001). Heart rate measured in the office increased mildly with quintiles of PP/SV (P < 0.05). After adjusting for age, sex, body weight and office heart rate, DeltaSBP progressively increased with increasing quintiles of PP/SV (P for trend < 0.0001), whereas stroke volume decreased, paralleling the increase in left ventricular relative wall thickness (both P < 0.0001) and left ventricular mass index (P < 0.05). The significant increase in effective arterial elastance with quintiles of PP/SV was also independent of peak systolic BP, in addition to age, sex, heart rate and body weight. CONCLUSIONS: The difference between office BP and ambulatory BP, an estimate of the white-coat effect, is strongly associated with increased arterial stiffness, evaluated by a two-element fluid system accumulator. PMID- 17351376 TI - Reduced levels of N-terminal-proatrial natriuretic peptide in hypertensive patients with metabolic syndrome and their relationship with left ventricular mass. AB - OBJECTIVES: The metabolic syndrome (MS) is associated with left ventricular hypertrophy (LVH). Previous evidence has shown that LVH is favoured by low levels of atrial natriuretic peptide (ANP), independently from blood pressure (BP), in hypertension. Although levels of natriuretic peptides are known to be lower in obesity, plasma ANP levels have not yet been assessed in MS. We aimed to assess the ANP levels and their relationship with left ventricular mass (LVM) in patients affected by MS. METHODS: One hundred and twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, echocardiographical and biochemical parameters, and levels of both N terminal (NT)-proANP and alphaANP were assessed. RESULTS: Hypertensive patients affected by MS had higher LVM and increased frequency of LVH. NT-proANP levels were significantly lower in MS, independent of waist circumference (WC). Log(NT proANP) levels were significantly inversely related to left ventricular mass index (LVMI) (beta = -0.360, P < 0.001) and LVM/height (beta = -0.370, P < 0.001) in the whole hypertensive population by multiple linear regression analysis. The relationship of log(NT-proANP) with LVM was more enhanced in patients with MS. CONCLUSIONS: The present study demonstrates that levels of NT-proANP are significantly reduced in hypertensive patients affected by MS, and they are significantly inversely related to the increased LVM observed in these patients. Our findings, while supporting previous experimental and clinical evidence of the antihypertrophic role of ANP in hypertension, may help to identify one of the possible mechanisms directly underlying LVH in MS. PMID- 17351377 TI - Effects of telmisartan on fat distribution in individuals with the metabolic syndrome. AB - BACKGROUND: Visceral fat obesity plays an essential role in the clustering of atherosclerotic multiple risk factors in the metabolic syndrome. Telmisartan, an angiotensin II type 1 receptor blocker, has partial agonistic properties for peroxisome proliferator-activated receptor gamma, which is a key regulator of adipocyte differentiation and function. METHODS: This study aimed to clarify the impact of telmisartan on fat distribution and insulin sensitivity in the metabolic syndrome. In this open-label, prospective, randomized study, patients with the metabolic syndrome (waist circumference: men >or= 85 cm, women >or= 90 cm) were treated either with amlodipine (n = 26) or with telmisartan (n = 27) for 24 weeks, and fat distribution and insulin sensitivity were determined. RESULTS: Systolic and diastolic blood pressure were decreased in both groups to a comparable level. However, insulin and glucose levels during an oral 75 g glucose loading were decreased only in the telmisartan group. The visceral fat area, determined by abdominal computed tomography scan, was reduced in the telmisartan group after 24 weeks' treatment, but the subcutaneous fat area did not change in either group. CONCLUSION: The results imply that telmisartan could treat both the hemodynamic and metabolic aberrations seen in patients with the metabolic syndrome, improving insulin resistance and glucose intolerance at least partly through visceral fat remodeling. PMID- 17351378 TI - Babies, pre-eclamptic mothers and grandparents: a three-generation phenotyping study. AB - OBJECTIVES: Pre-eclampsia (PE) is associated with an increased incidence of cardiovascular disease in later life. Daughters of PE mothers have an increased risk of developing the disease; recent epidemiological data suggest a (grand)paternal contribution. We have directly studied the parents of 673 women with stringently defined PE in relation to their daughters' disease. METHODS: (Grand)parental medical history, current medication and blood pressure (using an Omron 705 automated monitor) were recorded, with obstetric history for the grandmother, including directly verified pregnancy hypertension. RESULTS: The age of the 649 participating grandmothers was 55.5 +/- 7.5 years (mean +/- SD) and that of the 542 participating grandfathers was 58.0 +/- 7.3 years. Essential hypertension (EHT) requiring therapy was present in 23.4% of the grandmothers and 22.8% of the grandfathers. Patients had moderate to severe PE; a quarter were delivered before 34 weeks' gestation. A third of the babies had birthweights below the third centile; the perinatal mortality rate was 2.1%. Grandparental absolute systolic pressures and EHT status were highly significant determinants of maternal systolic pressure during gestation (F = 11.8, P < 0.001; F = 8.91, P = 0.003, respectively); maternal body mass index (BMI) had less effect. A similar, less marked, pattern was seen for diastolic pressure (F = 6.01, P = 0.014; F = 11.50, P < 0.0001). Grandmaternal EHT did not influence her daughter's systolic or diastolic pressure (P > 0.2 for both). CONCLUSIONS: A paternal, but not maternal, history of EHT is associated with increased risks of non-pregnant hypertension in the children, the risk being greater in daughters than sons. Pregnancy may unveil or exacerbate this effect, possibly reflecting underlying endothelial vulnerability. PMID- 17351379 TI - Blood pressure lowering after experimental cerebral ischemia provides neurovascular protection. AB - BACKGROUND: There is evidence that acutely elevated blood pressure (BP) after stroke is associated with increased cerebral hemorrhage and edema. Previous experiments in our laboratory have shown that candesartan 1 mg/kg administered after reperfusion in a model of hypertension after experimental ischemic stroke reduces neurovascular damage and improves outcome. These results could be either mediated by BP lowering or a BP-independent cerebrovascular protective effect. OBJECTIVES: To determine the contribution of BP lowering to the neurovascular protection previously reported with candesartan after stroke. METHODS: Male Wistar rats (280-305 g) underwent 3 h of middle cerebral artery occlusion (MCAO). At reperfusion, either hydralazine 1 mg/kg (n = 8), enalapril 5 mg/kg (n = 7) or enalapril 10 mg/kg (n = 8) were administered intravenously. BP was measured by telemetry for 2 days before and 24 h after MCAO. After neurological function was assessed, brain tissue was processed for infarct size and hemoglobin content analyses. RESULTS: Mean arterial pressure (MAP) increased from 92 to 124 mmHg immediately upon MCAO and decreased to 112 mmHg after reperfusion, remaining elevated for 24 h (P < 0.0001) in the saline group. Hydralazine reduced MAP (P = 0.048) and infarct size (53 versus 30%, P = 0.0083), and there was a trend towards decreased hemoglobin content. Enalapril 5 mg/kg did not significantly change MAP or other outcomes. Enalapril 10 mg/kg reduced MAP (P < 0.0001) and infarct size (53 versus 29%, P = 0.003). There was an intermediate effect on both hemoglobin content and neurological function, neither one was significant. The time course of BP lowering varied with each treatment. CONCLUSION: Acute BP lowering after reperfusion in acute ischemic stroke is an effective strategy to achieve neurovascular protection. The rate, extent and mechanism of BP lowering may determine the magnitude of protection. PMID- 17351380 TI - Involvement of thromboxane A2 receptor in the cerebrovascular damage of salt loaded, stroke-prone rats. AB - BACKGROUND: Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded, stroke-prone, spontaneously hypertensive rats (SHRSP). Thromboxane A2 (TP) receptor stimulation by 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) is involved in the process of vascular inflammation. OBJECTIVE: In the present study, we examined the involvement of TP receptor in the development of cerebrovascular damage in salt-loaded SHRSP. METHODS: Nine week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without ONO-8809 treatment (a TP receptor antagonist) for 5 weeks. Blood pressure, mortality, and the parameters of cerebrovascular inflammation and damage were compared between the groups. Moreover, we examined the effect of 8-iso-PGF2alpha infusion on cerebrovascular injury of SHRSP. RESULTS: High salt intake in SHRSP significantly increased blood-brain barrier impairment and early mortality, which were suppressed by ONO-8809 treatment independent of changes in blood pressure. Salt loading also significantly increased superoxide production in basilar arteries of SHRSP, which was suppressed by ONO-8809 treatment. Macrophage accumulation and matrix metalloproteinase-9 (MMP-9) activity in the stroke-negative area in the contralateral cerebral cortex to the stroke lesion of salt-loaded SHRSP and 8-iso PGF2alpha-treated SHRSP were significantly reduced by ONO-8809 treatment. The ONO 8809 treatment prevented thinning of the vessel layer in cerebral arterioles of salt-loaded SHRSP and 8-iso-PGF2alpha-treated SHRSP. CONCLUSIONS: These results suggest that TP receptor stimulation by 8-iso-PGF2alpha may involve salt loading induced stroke through activation of cerebrovascular inflammation and damage. PMID- 17351381 TI - Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies. AB - OBJECTIVE: To investigate whether a threshold exists for cardiovascular risk in type 2 diabetic patients with hypertension, the association between renal function and cardiovascular risk was examined across the entire physiological range of serum creatinine. DESIGN AND METHODS: The RENAAL and LIFE studies enrolled 1513 and 1195 patients with type 2 diabetes and hypertension, respectively. The relationship between baseline serum creatinine and the risk for a composite outcome of myocardial infarction, stroke or cardiovascular death was examined using Cox regression models. To adjust for heterogeneity between studies and treatment groups, these factors were included as strata when applicable. The analyses were conducted with adjustment for age, gender, smoking, alcohol use, blood pressure, heart rate, total and high-density lipoprotein (HDL) cholesterol, hemoglobin, albuminuria and prior cardiovascular disease. RESULTS: The hazard ratios across the baseline serum creatinine categories < 0.9 mg/dl, 0.9-1.2 mg/dl, 1.2-1.6 mg/dl, 1.6-2.8 mg/dl and >or= 2.8 mg/dl were 0.51 (95% confidence interval 0.34, 0.74), 0.74 (0.55, 1.00), 1.00 (reference), 1.24 (0.96, 1.59) and 1.67 (1.17, 2.91), respectively. Baseline serum creatinine (per mg/dl) strongly predicted the composite cardiovascular endpoint in LIFE [2.82(1.74,4.56), P < 0.001], RENAAL [1.41(1.12,1.79), P < 0.001], as well as the combined studies [1.51(1.21,1.87), P < 0.001]. CONCLUSION: A progressively higher risk for the composite cardiovascular endpoint was observed with incremental baseline serum creatinine in type 2 diabetic patients with hypertension, even within the normal range. Thus, there appears to be no serum creatinine threshold level for an increased cardiovascular risk. Baseline serum creatinine was a major independent risk factor for cardiovascular disease (www.ClinicalTrials.gov number NCT00308347). PMID- 17351382 TI - Racial differences in renal vascular response to angiotensin blockade with captopril or candesartan. AB - OBJECTIVE: We compared the renal vascular response to captopril and candesartan among nondiabetic, normotensive black and white participants to explore angiotensin-converting enzyme-independent generation of angiotensin II. METHODS: Thirteen black individuals and 10 white individuals in low-salt balance were given captopril and candesartan on sequential study days, and the renal plasma flow responses to these agents were measured. RESULTS: Consistent with our prior observations, white individuals demonstrated a strong, significant correlation between responses to these drugs (r = 0.78, P = 0.008) and a significantly greater increase in the renal plasma flow in response to candesartan compared with captopril (104.2 +/- 26.8 versus 52.4 +/- 24.3 ml/min per 1.73 m; P = 0.03). In black participants, however, no correlation between responses to captopril and to candesartan was observed (r = 0.22, P = 0.47) and there was no difference in the renal plasma flow response between the two drugs (90.4 +/- 13.0 versus 80.4 +/- 15.3 ml/min per 1.73 m; P = 0.59). The difference in the response to the two drugs was significantly higher among white participants compared with black participants (P = 0.03). CONCLUSION: We confirmed the contribution of an angiotensin-converting enzyme-independent pathway for angiotensin II generation in the kidneys of nondiabetic, normotensive white, but not black, individuals. PMID- 17351383 TI - Discrepancy between improvement of insulin sensitivity and that of arterial endothelial function in patients receiving antihypertensive medication. AB - OBJECTIVES: We evaluated whether the changes in the insulin sensitivity observed in hypertensive patients following treatment with an angiotensin II receptor blocker (candesartan) or calcium-channel antagonist (amlodipine) might be related to improvement of the endothelial function (END) and/or plasma level of high sensitive C-reactive protein (CRP) following such treatment. METHODS AND RESULTS: Seventy-one hypertensive patients (age: 58 +/- 10 years) without obvious target organ damage were allocated randomly to treatment with either candesartan at the dose of 8 mg/day or amlodipine at the dose of 5 mg/day. At the start and end of the 8-month treatment period, the homeostasis model assessment index of insulin resistance (HOMA-IR index), plasma CRP and END, as assessed by changes in the forearm blood flow in reactive hyperemia, were determined. While significant improvement of END was observed in patients receiving either drug, only candesartan, but not amlodipine, also reduced the plasma CRP and HOMA-IR index (2.13 +/- 1.92 --> 1.53 +/- 1.47, P < 0.05). In the patients receiving treatment with candesartan, stepwise multivariate linear regression analysis revealed that the percent change in the HOMA-IR index was significantly and independently correlated with that in the plasma CRP (beta = 0.38, P < 0.05), but not with that in END: CONCLUSION: Improvement of the END alone by the antihypertensive medication might not entirely explain the improvement of the insulin sensitivity observed in these patients. Additional mechanisms may be involved, and the anti inflammatory effects of the medication observed in patients treated with candesartan may also be related, at least in part, to the observed improvement of insulin sensitivity. PMID- 17351384 TI - Low-dose spironolactone in the management of resistant hypertension: a surveillance study. AB - METHODS: We have conducted an open observational study of the use of spironolactone 25-50 mg in the management of patients with resistant hypertension. This drug was recommended in 133 patients who were already receiving an angiotensin-blocking drug in addition to other therapies. RESULTS: Of these, three defaulted from follow-up and 11 could not tolerate spironolactone. We therefore have outcome data on 119 patients. The addition of spironolactone (median dose 25 mg) was associated with a mean (SD) fall in systolic blood pressure of 21.7 mmHg (24.0; P < 0.001) and diastolic blood pressure of 8.5 mmHg (14.9; P < 0.001). In two patients spironolactone had to be discontinued on account of a rise of serum potassium to above 6.0 mmol/l, whereas overall the mean increase in serum potassium was 0.3 mmol/l. CONCLUSION: With careful monitoring of plasma electrolytes, spironolactone at a low dose is an effective add-in drug in patients with hypertension resistant to a regime that includes an angiotensin-blocking agent. PMID- 17351385 TI - Ethnic disparities in malignant hypertension: further observations. PMID- 17351387 TI - European Society of Hypertension Working Group on Obesity: background, aims and perspectives. PMID- 17351388 TI - Histone deacetylase inhibitors for epigenetic therapy of cancer. AB - Histone acetylation and histone deacetylation play key roles in the epigenetic regulation. Thus, inhibition of deacetylation controlled by histone deacetylases may result in chromatin remodeling, upregulation of key tumor repressor genes, differentiation or apoptosis. Therefore many naturally occurring and synthetic histone deacetylase inhibitors have been shown to display potent anticancer activities in preclinical studies. The exact mechanism by which histone deacetylases exert their effect, however, is still obscure; in any case it is more complicated than originally understood. Although several representatives of this novel class of therapeutic agents are currently at early stages of clinical development, rational design leading to highly selective histone deacetylase inhibitors against histone deacetylase isoforms will not only probably offer more potent anticancer drugs, but also critical insights into their mechanism of action. PMID- 17351389 TI - Src, chemoresistance and epithelial to mesenchymal transition: are they related? AB - The Src family of nonreceptor tyrosine kinases regulates numerous cellular processes, including proliferation, differentiation, migration, survival and angiogenesis. In solid tumors, Src is frequently aberrantly active, and promotes tumor progression and metastasis. Although multiple Src functions may contribute to metastasis, recently Src has been shown to play a role in epithelial to mesenchymal transition. Increased Src activity promotes this process and inhibition of Src suppresses epithelial to mesenchymal transition. Although the molecular events causing epithelial to mesenchymal transition are becoming well defined, the processes in tumor cells that trigger the onset of this phenotype remain unclear. Recent studies have associated epithelial to mesenchymal transition with the development of chemoresistance. Src has also been shown to be involved in chemoresistance of cancer cells. The activation of Src in chemoresistant cells is related to an increase in motility, invasiveness and detachment, all phenotypes characteristic both of Src activation and of epithelial to mesenchymal transition. This review focuses on upregulation of Src in cancer as it relates to chemoresistance and epithelial to mesenchymal transition. PMID- 17351390 TI - RNA interference targeting the R2 subunit of ribonucleotide reductase inhibits growth of tumor cells in vitro and in vivo. AB - RNA interference, a posttranscriptional gene-silencing mechanism, has received considerable attention for its potential as a new therapeutic strategy to treat human diseases and conditions including cancer. Various studies have supported a role for the R2 subunit of ribonucleotide reductase in cancer progression and metastasis. Short interfering siRNA 1284 was designed to target R2. In vitro studies, in which three different human tumor cell lines (A498, HT-29 and A2058) were transfected with short interfering siRNA 1284, demonstrate sequence-specific down-regulation of R2, which coincides with a decrease in cell proliferation, and cell cycle inhibition. In vivo studies with xenograft mouse models, generated from the same tumor cell lines, indicate that treatment with short interfering siRNA 1284 leads to inhibition of tumor growth and this effect was found to be dose dependent. Taken together, these results suggest that short interfering siRNA 1284, targeting R2, has great potential to serve as a therapeutic agent towards the treatment of human cancers. PMID- 17351391 TI - Correlations between the activities of 19 standard anticancer agents, antioxidative enzyme activities and the expression of ATP-binding cassette transporters: comparison with the National Cancer Institute data. AB - The aim of this work was to determine the functional activities of four different antioxidative enzymes (glutathione reductase, glutathione-S-transferase, glutathione peroxidase, thioredoxin reductase) and the protein expression of three ATP-binding cassette transporters (P-glycoprotein, multidrug resistance protein 1, multidrug resistance protein 2) in a panel of 14 human cancer cell lines. Enzyme activities and transporter expression were then correlated with the in-vitro cytotoxic activities (GI50 values) of 19 standard antitumor drugs. Analogous data from the National Cancer Institute were used for comparison. The GI50 values of the platinum complexes, alkylating agents, antimetabolites, topoisomerase inhibitors and antimitotic drugs were determined by crystal violet or 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assay. Standard enzymatic assays employed to measure the glutathione peroxidase, glutathione-S transferase, glutathione reductase and thioredoxin reductase activities. The protein expression of the ATP-binding cassette transporter proteins was investigated by the Western-blot method. The delta method was used to normalize the data before bivariant correlation analysis. Only a few correlations between enzyme and cytotoxic activities of the antitumor agents were found. The GI50 values for melphalan and camptothecin correlated positively with the activity of glutathione-S-transferase, whereas GI50 values for methotrexate correlated positively with the cellular activities of both glutathione reductase and thioredoxin reductase. A significant correlation between glutathione reductase and thioredoxin reductase activities was found in our panel of cell lines. Neither P-glycoprotein nor multidrug resistance protein 2 expression could be detected by Western blot analysis in any cell lines investigated, but multidrug resistance protein 1 was consistently observed in all but four lines. Multidrug resistance protein 1 expression correlates positively with the GI50 values of several drugs, e.g. vinblastine and etoposide, and negatively with the GI50 values of 5-fluorouracil. The results confirm the complexity of resistance to antitumor agents and show that the GSH-thioredoxin system alone is not a good indication of intrinsic resistance for many of these anticancer drugs. PMID- 17351392 TI - Inhibition of adenosine monophosphate-activated protein kinase induces apoptosis in multiple myeloma cells. AB - In this study, we show that adenosine monophosphate-activated protein kinase (AMPK) is expressed and activated in multiple myeloma cells. The inhibition of AMPK induced growth arrest and reduction of cell viability in the cell viability assay using the water-soluble tetrazolium salt 4-[3-(4-iodophenyl)-2-(4 nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1 assay). Induction of apoptosis was determined by annexin-V and propidium iodide staining. The prevention of apoptosis using the pancaspase inhibitor ZVAD-fmk and caspase-3 cleavage upon incubation with the AMPK inhibitor (AMPKI) is shown. Furthermore, incubation of myeloma cells with AMPKI resulted in the downregulation of pAMPK, Mcl-1 and Bcl-xL. Coincubation of AMPKI and melphalan led to a strong additional increase of apoptosis in myeloma cells. We conclude that AMPKI has a strong antimyeloma activity in vitro and represents a new targeted strategy in the treatment of multiple myeloma. PMID- 17351393 TI - G1 arrest induction represents a critical determinant for cisplatin cytotoxicity in G1 checkpoint-retaining human cancers. AB - Cisplatin has been used effectively to treat various human cancer types; yet, the precise mechanism underlying its cytotoxicity remains unknown. In eukaryotes, progression through G1 is monitored by a checkpoint, which executes G1 arrest in the event of DNA damage to allow time for repair before initiating DNA replication. The retinoblastoma tumor suppressor gene is an integral component of the mammalian G1 checkpoint. The utility of the retinoblastoma gene as a therapeutic for human cancers has been investigated. Intriguingly, the cytotoxicity profile of the retinoblastoma gene therapy closely parallels the clinical targets of cisplatin. It prompted an investigation into the potential role of the checkpoint-induced G1 arrest in cisplatin cytotoxicity. Here, the evidence that G1 arrest induction represents a critical step in cisplatin-induced lytic path is presented. First, cisplatin-treated human cancer cells undergo a prolonged G1 arrest before dying. Second, triggering G1 arrest via infection with a recombinant adenovirus expressing the human retinoblastoma gene is sufficient to potentiate lethality in the absence of cisplatin. Third, the extent of the lethality induced correlates with the G1-arresting potential of the ectopically expressed human retinoblastoma polypeptide. Fourth, human cancer cells resistant to cisplatin do not undergo G1 arrest despite cisplatin treatment. The above mechanism may be exploited to develop therapeutics that preserve the efficacy of cisplatin yet bypass its mutagenicity associated with the formation of secondary tumors. PMID- 17351394 TI - Differential regulation of DNA repair protein Rad51 in human tumour cell lines exposed to doxorubicin. AB - Radiotherapy and chemotherapy often induce DNA double-strand breaks in both normal and malignant cells. The proteins involved in the repair of such lesions are central to cancer prognosis and treatment, as they can be overexpressed in many cancers, accelerating malignant transformation and increasing repair capacity, potentially leading to cellular resistance. If malignant cells can be selectively targeted repair proteins could also be candidates for targeted therapy. In this study, two keyplayers in eukaryotic DNA double-strand break repair, Rad51 and DNA-dependent protein kinase catalytic subunit, were analysed in noncancerous human breast cells (MCF12A) and the breast cancer cell lines (MDA MB 231 and MCF7) in response to treatment with doxorubicin. A cell cycle independent increase in Rad51 protein levels (a recombinase involved in homologous recombination repair) was observed 24 and 48 h after treatment in MDA MB 231 and MCF12A when exposed to low levels of doxorubicin, whereas MCF7 cells displayed a continuous decrease in Rad51 protein with increasing drug concentration. DNA-dependent protein kinase catalytic subunit, which is involved in nonhomologous end joining of DNA lesions, remained unaltered under all conditions tested. Topoisomerase II-alpha protein, the primary target of doxorubicin, was upregulated at low concentrations of doxorubicin in all cell lines tested. Here we show that Rad51 protein levels can be differentially regulated in normal and malignant breast cell lines in response to doxorubicin, independent of cell cycle state. These observations have direct relevance to chemosensitivity and add an additional prognostic factor that could be taken into account when designing targeted therapeutic regimes. PMID- 17351395 TI - The TKTL1 gene influences total transketolase activity and cell proliferation in human colon cancer LoVo cells. AB - A plasmid carrying DNA to be transcribed into a small interfering RNA against transketolase-like-1 mRNA was constructed and transfected into a human colon cancer cell line. The mRNA expression of transketolase gene family in the human colon cell line was determined by real-time polymerase chain reaction. The effect of anti-transketolase-like-1 small interfering RNA on cell proliferation and cell cycle in the human colon cancer cell line cells was detected by flow cytometry and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide. The transketolase-like-1 gene was significantly downregulated in human colon cancer cell line cells transfected with small interfering RNA transketolase-like-1 constructs compared with the cells transfected with control vector and the cells without transfection. In addition, the anti-transketolase-like-1 small interfering RNA construct significantly decreased the level of transketolase in the transfected human colon cancer cell line cells, arrested them in G0/G1 phase and substantially inhibited cell proliferation. No significant difference was found in the other two genes (transketolase and transketolase-like-2 genes) between the transfected human colon cancer cell line cells and the controls (P>0.05). Our data demonstrated that the transketolase-like-1 gene plays an important role in total transketolase activity and in the cell proliferation of human colon cancer. Transketolase-like-1 may serve as a target for novel anticancer therapies. PMID- 17351396 TI - ARC-111 inhibits hypoxia-mediated hypoxia-inducible factor-1alpha accumulation. AB - ARC-111, a small-molecule topoisomerase I inhibitor, is a potent cytotoxic drug against multiple human cancer cell lines under normoxic conditions (Li et al., Cancer Res 2003; 63:8400-8407). In this study, we explore the potential of ARC 111 as a hypoxia-inducible factor-1alpha inhibitor under hypoxic conditions. The transcription factor, hypoxia-inducible factor-1alpha, is an essential regulator of tumorigenesis and an attractive molecular target for cancer therapy. We demonstrate that ARC-111 specifically inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1alpha, but not other short half-life proteins in multiple human cancer cell lines. ARC-111 inhibits hypoxia-inducible factor 1alpha protein synthesis specifically and does not inhibit protein synthesis globally. We demonstrate that inhibition of hypoxia-inducible factor-1alpha accumulation by ARC-111 is independent of proteasomal degradation. In addition, we demonstrate using topoisomerase I-resistant cell lines that topoisomerase I is required for ARC-111-mediated hypoxia-inducible factor-1alpha inhibition. Experiments performed with nocodazole indicate that ARC-111 inhibits hypoxia inducible factor-1alpha accumulation in a cell-cycle-independent manner. Analysis of AKT and mammalian target of rapamycin phosphorylation reveals that ARC-111 does not exhibit inhibitory effect on the phosphatidylinositol-3-kinase AKT mammalian target of rapamycin signaling pathway. It has been previously shown that topotecan, a topoisomerase I inhibitor, can also modulate hypoxia-induced hypoxia-inducible factor-1alpha accumulation (Rapisarda et al., Cancer Res 2003; 64:1475-1482). In addition to inhibiting hypoxia-induced accumulation of hypoxia inducible factor-1alpha, ARC-111 exhibits antiproliferative effects against multiple human cancer cell lines. We demonstrate that topoisomerase I is required for the antiproliferative effects of ARC-111. Antiproliferative effects of ARC 111, however, are oxygen-independent, which is distinguishable from inhibition of hypoxia-inducible factor-1alpha accumulation by ARC-111, which is only observed under hypoxia. The results indicate that inhibiting hypoxia-inducible factor 1alpha accumulation and exhibiting antiproliferation of ARC-111 are through distinct mechanisms of action, which reinforce the potential anticancer effect of ARC-111 on hypoxic tumors. PMID- 17351397 TI - Antitumor properties of diastereomeric and geometric analogs of vitamin D3. AB - Analogs of 1,25-dihydroxyvitamin D3 with a reversed configuration at C-1 or C-24 and E or Z geometry of the double bond at C-22 in the side chain or at C-5 in the triene system were examined for their antiproliferative activity in vitro against a spectrum of various human cancer cell lines. The analogs coded PRI-2201 (calcipotriol), PRI-2202 and PRI-2205, such as calcitriol and tacalcitol (used as a referential agents), revealed antiproliferative activity against human HL-60, HL-60/MX2, MCF-7, T47D, SCC-25 and mouse WEHI-3 cancer cell lines. The toxicity studies in vivo showed that PRI-2202 and PRI-2205 are less toxic than referential agents. Even at total doses of 2.5-5.0 mg/kg distributed during 5 successive days, no changes in body weight were observed. Calcitriol and tacalcitol showed toxicity in the same protocol at 100 times lower doses. Calcipotriol was lethal to all mice after administration of a total dose of 5.0 mg/kg. The analog PRI 2205 appeared to be more active in mouse Levis lung cancer tumor growth inhibition than calcitriol, calcipotriol or PRI-2202. This analog did not reveal calcemic activity at doses which inhibit tumor growth in vivo nor at higher doses. PMID- 17351398 TI - Intratumoral delivery of paclitaxel-loaded poly(lactic-co-glycolic acid) microspheres for Hep-2 laryngeal squamous cell carcinoma xenografts. AB - The introduction of induction chemotherapy provides an expectation of laryngeal function preservation without reduction in survival for patients with advanced laryngeal squamous cell carcinoma. The antitumor activity of conventional intravenous chemotherapy, however, is limited by systemic toxicity. The polymeric drug system delivered locally provides a novel modality of increasing therapeutic concentrations of drug for a prolonged period while decreasing systemic levels. In the current study, paclitaxel-loaded sustained-release microspheres were developed using poly(lactic-co-glycolic acid) as a drug carrier. Intratumoral administration of paclitaxel in the formulation of polymer showed enhanced efficacy against laryngeal squamous cell carcinoma in nude mice compared with conventional paclitaxel injection via the intratumoral or intraperitoneal route. No significant toxic reactions were observed in the experiment. Immunohistochemical findings indicated that paclitaxel exhibited antiangiogenic activity by inhibiting the expression of basic fibroblast growth factor and vascular endothelial growth factor within the tumor. Moreover, this effect could be better exploited via localized delivery of polymeric paclitaxel. In conclusion, direct administration of polymeric drug system at the tumor sites proved to be promising for the treatment of laryngeal carcinoma. PMID- 17351399 TI - Inhibition of five xenografted human cancers and two murine cancers by the tripeptide tyroservatide. AB - The tripeptide tyroservatide (tyrosyl-seryl-valine, pTyr-Ser-Val-NH2) has been shown to have antitumor effects on experimental hepatocarcinoma. This study aimed to observe the effects of tyroservatide on other five human carcinomas: A549 (nonsmall cell lung carcinoma), BGC-823 (gastric cancer), MCF-7 (breast cancer), K562 (leukemia), A375 (melanoma) and two murine cancers: Lewis lung cancer and B16 (melanoma) in vivo. In vivo nude mice bearing xenografts of five different human tumors or C57BL/6 mice bearing xenografts of two different murine tumors were given daily intraperitoneal injections of tyroservatide or saline as controls, after tumor implantation. The inhibition of xenografts was determined by calculating the tumor volume and measuring tumor weight. Tyroservatide could significantly inhibit the growth of human lung carcinoma A549, human leukemia K562 and human melanoma A375 in nude mice (P<0.05). In addition, tyroservatide significantly inhibited the subcutaneous tumor growth of Lewis lung carcinoma and B16 melanoma (P<0.05). Tyroservatide, however, could not significantly suppress xenografts of BGC-823 and MCF-7 in nude mice (P>0.05). The results obtained indicate that tyroservatide exhibits different effects on different tumors, which will provide clinical applications guidance of tyroservatide as an anticancer drug. PMID- 17351400 TI - A phase I dose-escalation study of S-1 plus carboplatin in patients with advanced non-small-cell lung cancer. AB - We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer. Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin on day 1 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 5/65; level 2, 5/80; level 3, 6/80 [carboplatin (area under the curve, mg/ml/min)/S-1 (mg/m/day)]. The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle. Twelve patients were enrolled in this study. The main grade 3 or grade 4 toxicities observed during the first cycle were neutropenia (41%), thrombocytopenia (41%) and transaminase elevation. Two of three patients in level 2 had dose-limiting toxicity and this level was considered the maximum tolerated dose. Level 1 was selected as the recommended dose. Objective responses were seen in four patients (response rate 33%). The combination of S-1 plus carboplatin is a feasible and well-tolerated regimen for the treatment of patients with advanced non-small-cell lung cancer. PMID- 17351401 TI - Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6 positive metastatic breast cancer: final results of a phase I study. AB - The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer. Anthracycline and taxane-pretreated patients with metastatic breast cancer that expressed CD44v6 received one single infusion of bivatuzumab mertansine and were observed for 21 days within one treatment course. Starting dose was 25 mg/m, while dose was escalated by increments of 25 mg/m. Patients who experienced a disease stabilization were eligible for further courses with bivatuzumab mertansine. Blood serum samples were taken throughout the treatment period for pharmacokinetic analysis. Twenty-four patients were treated at eight different dose levels (25-200 mg/m), seven of these patients received more than one course of bivatuzumab mertansine. Two dose-limiting toxicities occurred: one patient treated with 125 mg/m developed transient National Cancer Institute Common Toxicity Criteria grade 4 elevation of liver enzymes; another patient treated at 175 mg/m experienced National Cancer Institute Common Toxicity Criteria grade 3 vomiting. She died from renal failure, which might have been caused by deterioration of pre-existing renal insufficiency. The most common toxicities were transient and mild skin disorders in 75% of patients. As a consequence of one fatal toxic epidermal necrolysis that occurred in a study running in parallel, the clinical trials programme of bivatuzumab mertansine was discontinued. None of the patients developed antibodies against bivatuzumab mertansine. No objective responses were observed. Disease stabilization was achieved in 50% of patients independently of dose level. In conclusion, bivatuzumab mertansine targets CD44v6 and appears to stabilize heavily pretreated metastatic breast cancer that expresses CD44v6. The maximum tolerated dose could not be determined in this trial as the sponsor discontinued the clinical development of bivatuzumab mertansine. PMID- 17351402 TI - Gemcitabine and ifosfamide as a second-line treatment for cisplatin-refractory metastatic urothelial carcinoma: a phase II study. AB - Few treatment options are available for cisplatin-refractory urothelial carcinoma. We evaluated the efficacy and safety of a new regimen composed of gemcitabine and ifosfamide as a second-line salvage chemotherapy for the disease. The gemcitabine and ifosfamide regimen consists of gemcitabine 800 mg/m/day intravenously for 30 min on days 1, 8, and 15; ifosfamide 1500 mg/m/day intravenously for 24 h on days 8-10; and mesna 800 mg intravenously bolus before ifosfamide and 1500 mg/m/day intravenously for 24 h on days 8-11. Cycles are repeated every 28 days. Between 1998 and 2005, 23 patients (median age 66) unresponsive to cisplatin-based chemotherapy (n=10) or who had tumor progression within 6 months of a previous response to cisplatin-based therapy (n=13) were enrolled. The median interval between the two chemotherapy regimens was 1.8 months (range 0.9-5.6). In total, 82 treatment cycles (median 3, range 1-8) were given. The overall response rate was 22% (95% confidence interval 5-39) with one complete response and four partial responses. Twenty-one patients succumbed to the disease. The median progression-free survival and overall survival were 3.5 and 4.8 months, respectively. Grade 3 or 4 leukopenia and thrombocytopenia occurred in 10 and eight patients, respectively. One, two and two patients complicated with grade 3 vomiting, diarrhea and stomatitis were present, respectively. No grade 3 or 4 neurotoxicity or nephrotoxicity was seen in these patients. The gemcitabine and ifosfamide regimen has an acceptable toxicity profile, but shows insufficient clinical activity in patients with cisplatin refractory urothelial carcinoma to warrant further testing. PMID- 17351403 TI - QT prolongation and Torsades de Pointes in patients previously treated with anthracyclines. AB - Anthracyclines reduce myocardial repolarization reserve and might increase the risk for Torsades de Pointes a long time after treatment. We studied all the publications concerning Torsades de Pointes in patients previously treated with anthracyclines to investigate the clinical circumstances leading to this rare life-threatening complication. Our literature search yielded nine reports of 11 patients who had developed Torsades de Pointes anywhere from weeks to years following treatment with anthracyclines. One of the patients was hospitalized in our medical center. Risk factors and triggers for Torsades de Pointes, among other clinical aspects, were analyzed in each report. Most patients (n=10; 90.9%) were previously treated with anthracyclines owing to acute leukemias: acute myelogenous leukemia (n=5), acute lymphocytic leukemia (n=3) and acute promyelocytic leukemia (n=2). One patient was previously treated with anthracyclines owing to Hodgkin's lymphoma. Most patients were women (n=9; 81.8%). The most prevalent triggers for Torsades de Pointes were the administration of a QT-prolonging agent (n=10; 90.9%) and hypokalemia (n=9; 81.8%). Azole derivatives were the most prevalent of the QT-prolonging agents that triggered Torsades de Pointes (n=5; 45.5%). Although four patients suffered from anthracycline-induced left ventricular dysfunction and five other patients had only one or two questionable triggers for Torsades de Pointes, in only two of these cases the authors considered previous treatment with anthracyclines as a risk factor for Torsades de Pointes. Previous treatment with anthracycline is an underestimated risk factor for Torsades de Pointes. Possible triggers includes azole derivatives, other QT-prolonging agents and hypokalemia. Women patients are particularly at risk. PMID- 17351404 TI - The use of white blood cell count and left shift in the diagnosis of appendicitis in children. AB - BACKGROUND: The use of white blood cell (WBC) count and left shift in the diagnosis of appendicitis in pediatric patients is unproven. It is commonly thought that children with appendicitis have an elevated WBC count with a left shift; however, most data supporting this belief stem from studies conducted on appendicitis in adults, not children. The purpose of this investigation was to determine the value of WBC count and differential in the diagnosis of appendicitis in children presenting to the emergency department (ED) with acute abdominal pain. METHODS: Seven hundred twenty-two pediatric ED patients with a primary complaint of nontraumatic abdominal pain were identified by prospective and retrospective methods. White blood cell count with differential was performed on patients with history and physical examination findings that were felt to warrant laboratory investigation. Results of WBC counts were determined as low, normal, or high, with or without a left shift, based on normal age-related values per laboratory protocol for pediatric patients. RESULTS: The diagnosis of appendicitis was made in 10.2% of all patients presenting to the ED with acute abdominal pain. Thirty percent of toddlers (1-3.9 years) with high WBC counts had appendicitis, whereas 0% of toddlers with low WBC counts and 4.8% of toddlers with normal WBC counts had appendicitis (chi = 6.5, P = 0.04). A normal WBC count did not rule out appendicitis in toddlers; however, the negative predictive value (NPV) for normal or low WBC count was high (NPV = 95.6%). In the child age group (4-11.9 years), high WBC count was both sensitive and specific for the diagnosis of appendicitis in children (sensitivity = 71%, specificity = 72%), and the NPV for normal or low WBC count was high (NPV = 89.5%). Lastly, 43.9% of adolescents (12-19 years) with high WBC counts had appendicitis, whereas 0% of adolescents with low WBC counts and 8.3% of adolescents with normal WBC counts had appendicitis (chi = 37.3, P < 0.001). The NPV for a low or normal WBC count was also high in the adolescent group (NPV = 91.9%). Left shift was also strongly associated with appendicitis. Among toddlers, 40% of patients with a left shift had appendicitis, whereas 1.8% of toddlers without a left shift had appendicitis (chi = 25.7, P < 0.001, NPV = 98.2%). Similarly, left shift was strongly associated with appendicitis in children and adolescents. Among children, 54.3% of patients with a left shift had appendicitis, whereas 5.4% of children without a left shift had appendicitis (chi = 67.8, P < 0.001, NPV = 90.5%). Among adolescents, 53.5% of patients with a left shift had appendicitis, whereas 6.1% of adolescents without a left shift had appendicitis (chi = 72.3, P < 0.001, NPV = 93.9%). In patients with a left shift, 51.2% had appendicitis, whereas 3.7% of patients without a left shift had appendicitis (chi = 226.2; P < 0.001, NPV = 96.3%). In all patients with appendicitis, elevated WBC counts had a sensitivity of 67% and a specificity of 80%. Using left shift alone as an indicator for appendicitis was associated with a sensitivity of 59% and a specificity of 90%. However, when a high WBC count and left shift were combined, the sensitivity climbed to 80%, and specificity remained at 79%. The sensitivity fell to 47% when both a high WBC count and left shift were analyzed, and specificity climbed to 94%. The positive likelihood ratio for a high WBC count and left shift was 9.8. CONCLUSIONS: The determination of WBC count and differential is useful in the diagnosis of appendicitis in children presenting to the ED with nontraumatic acute abdominal pain, regardless of age. High WBC counts and left shift are independently, strongly associated with appendicitis in children aged 1 to 19 years. In fact, for this subset of patients older than 4 years, the most common diagnosis in the setting of an elevated WBC count was appendicitis. The presence of an increased WBC count or left shift carries with it a high sensitivity (79%), and the presence of both high WBC count and left shift has the highest specificity (94%). These values are, therefore, helpful in the diagnosis and exclusion of appendicitis. Although not absolute, the WBC count and left shift can be helpful in the diagnosis and exclusion of appendicitis. PMID- 17351405 TI - Pediatric and neonatal transport teams with and without a physician: a comparison of outcomes and interventions. AB - OBJECTIVE: To determine whether a transport team composed of advanced practice nurses could function as effectively as a physician-nurse team, as measured by patient outcome. DESIGN: Observational cohort study. SETTING: The interfacility transport team at a tertiary care children's hospital. PATIENTS AND OTHER PARTICIPANTS: Fourteen transport nurses and 539 patients. METHODS: A transport team was studied during a previously planned change in composition from a physician-nurse team to a nurse-nurse team. Data were recorded by transport nurses and by subsequent review of the medical record during two 4-month periods, 1 before and 1 after the team change. Pediatric risk of mortality scores (a marker for degree of illness) were assigned for the periods before, during, and after transport. Transport time intervals, demographic data, and patient outcomes were also recorded. Data were assessed using frequency tables for discrete variables, as well as mean and standard deviation for continuous variables. For identification of group differences, chi test was used. MAIN OUTCOME MEASURES: Mortality, transport-related morbidity, overall transport times and interval times, and outcome of procedures performed by transport nurses. RESULTS: Five hundred thirty-nine data sheets were received: 228 before (group 1) and 311 after (group 2) the team change. Physicians attended 128 (56.1%) group 1 transports and 15 (4.82%) group 2 transports. There were no significant differences in mean pediatric risk of mortality scores between group 1 and group 2 patients. Mortality was equivalent. Group 2 transport times were significantly shorter than group 1 times. Transport nurses performed 8 intubations; all were successful. CONCLUSIONS: Outcomes for the 2 types of teams were equivalent. Nonphysician teams responded more quickly and spent less time at the referring facility. PMID- 17351406 TI - Efficacy of short-term intravenous antibiotic in neonates with urinary tract infection. AB - BACKGROUND: Recent studies have questioned the use of prolonged intravenous treatment in neonates with urinary tract infection (UTI). The aim of the present study was to examine the clinical course of neonates with UTI with special attention paid to the rates of bacteremia and meningitis and to determine the efficacy of short-term intravenous antibiotic. METHODS: Retrospective review of clinical charts of neonates admitted for UTI. Patients were treated first intravenously with a beta-lactam antibiotic and gentamicin. Treatment was completed orally. RESULTS: One hundred seventy-two neonates (median age, 19 days) were included. Of 129 blood cultures carried out, 16 (12.4%) were positive. Analysis of cerebrospinal fluid was performed in 75 patients; none of the cultures was positive. Forty-nine patients (28.5%) were treated with ampicillin and gentamicin and 105 (61%) with amoxicillin-clavulanate and gentamicin. The median length of intravenous treatment was 4 days (P25: 3; P75: 6). Oral amoxicillin-clavulanate was used in the continuation phase in 75%. No treatment failure or relapse was detected. Eleven (8.7%) of 126 patients had renal scarring at 6 months. CONCLUSIONS: The clinical course in neonates with UTI treated with short-term intravenous antibiotic followed by oral treatment is highly favorable, both in short and long terms. The absence of meningitis and the good evolution of the associated bacteremias argue in favor of a review of the habitual diagnostic therapeutic protocol in neonates. PMID- 17351407 TI - The gap between pediatric emergency department procedural pain management treatments available and actual practice. AB - OBJECTIVES: To describe the spectrum of procedures performed and the pain management methods used in our pediatric emergency department. METHODS: Encounter records were retrospectively reviewed for all patients presenting to our pediatric emergency department, a stand-alone pediatric department with 20,000 patient visits per year, located in an urban, public teaching hospital, between March and June 2004. Data collected included patient demographics, provider type, procedures performed, and pharmacological pain management methods documented used. For intravenous catheter placement, the time lag between order and placement was noted. RESULTS: There were 1727 procedures performed in 1210 patients (18% of the total 6545 patients seen). Few to no patients undergoing venipuncture, intravenous catheter placement, fingersticks, intramuscular or subcutaneous injections, urethral catheterization, or nasogastric tube placement received pain management. The median time between order and placement of intravenous catheters was 30 minutes. Nearly all patients undergoing fracture reductions received procedural sedation with ketamine, and most of the lacerations repaired with sutures and nail avulsions received injected local anesthetic. Pain management of abscess incision and drainage and lumbar punctures was more variable. For lumbar punctures, of the patients aged 4 months or younger with a procedure note written, only 29% (7/24) had pain management documented versus 85% (22/26) of those aged 1 year or older (P < 0.0001). CONCLUSIONS: Several minor painful procedures are commonly performed in the emergency department without pharmacological pain management. There remains a gap between what we know to be effective, easily implemented pain management strategies, and what is actually practiced. We must work to close this gap. PMID- 17351408 TI - Emergency care for children in pediatric and general emergency departments. AB - OBJECTIVE: We examine the pediatric emergency department (ED) population and their clinical course in pediatric versus general EDs and identify potential factors contributing to differences in performance metrics between the 2 ED settings. METHODS: This was a retrospective analysis of pediatric visits to nationally representative EDs participating in the National Hospital Ambulatory Medical Care Survey from 1995 to 2002. Differences between pediatric and general EDs were examined in terms of patient characteristics and clinical course. RESULTS: Pediatric EDs treated more children with medical problems than general EDs, which treated more children with injuries. Visits by children to pediatric EDs were associated with longer wait times to see a physician (median, 40 vs. 25 minutes; P < 0.001) and longer stays in the ED (median, 130 vs. 98 minutes; P = 0.006). In multivariate analysis, the type of ED treating a pediatric patient was a significant determinant of wait time (percent change for pediatric EDs, 23.1; 95% confidence interval [CI], 3.4-46.6), length of stay (percent change for pediatric EDs, 23.0; 95% CI, 5.1-43.9), and rate of discharge (odds ratio for pediatric EDs, 0.75; 95% CI 0.61-0.92). Children in pediatric EDs seemed to be sicker than those in general EDs. CONCLUSIONS: These data provide the first glimpse of health care delivery to children seen in EDs nationally. Our findings indicate that significant differences exist between pediatric visits to pediatric and general EDs. These findings may be useful in establishing performance metrics for the care of ill and injured children in both pediatric and general EDs. PMID- 17351409 TI - Lemierre syndrome: a case report. AB - Lemierre syndrome is a condition that can have high morbidity and mortality, but if it is diagnosed early in a patient's workup, that is, in the ED, the morbidity and mortality can be significantly decreased. First described by Dr Andre Lemierre in 1936, Lemierre syndrome is a clinical condition, which presents as septic emboli in the internal jugular vein after an untreated pharyngitis. This condition can have significant morbidity and mortality; therefore, although it is not common in today's era of antimicrobials, it should still be considered and thought of to prevent the significant consequences that may occur from it. In this article, we will present a child who was admitted for fever, neck pain, lymphadenopathy, and lung abscesses which was diagnosed as Lemierre syndrome. This syndrome will be discussed so as to heighten clinical awareness of it. PMID- 17351410 TI - Gravel gut: small bowel perforation due to a blunt ingested foreign body. AB - The ingestion of foreign bodies remains a common occurrence in children. Most ingested foreign bodies pass spontaneously, although up to 1% will result in intestinal perforation. Specific foreign bodies such as sharp, pointed, or corrosive objects have been typically associated with perforation. The initial diagnosis of foreign body ingestion may be difficult in the absence of a witness, and the presentation of perforation in this situation difficult to distinguish from other causes of an acute abdomen. We report a case of ileal perforation due to a blunt ingested foreign body in a child in whom the diagnosis was unclear until laparotomy. This case highlights the difficulties in managing pediatric ingested foreign bodies, including the risk of perforation even with a blunt object. PMID- 17351411 TI - Emergency department presentation of acute disseminated encephalomyelitis. AB - Acute disseminated encephalomyelitis is an acute demyelinating disorder of the central nervous system that usually occurs in children and young adults. We report the case of an 8-year-old girl who presented to the emergency department with acutely altered mental status. Standard workup including head computed tomography, lumbar puncture, and routine chemistries was unrevealing. Magnetic resonance imaging revealed findings consistent with acute disseminated encephalomyelitis. Response to treatment with steroids was dramatic. Both the rapidity of onset and resolution of this patient's symptoms are unusual for the course of this disease. PMID- 17351412 TI - Vaginal laceration from a high-pressure water jet in a prepubescent girl. AB - OBJECTIVE: To document an unusual case of water douche injury in a prepubescent girl. DESIGN: Case report. RESULTS: After sitting atop a high-pressure water jet in a public fountain, a 9-year-old girl experienced pain and vaginal bleeding. She sustained a laceration high in her vaginal vault with an estimated total blood loss of 750 mL. Examination and vaginal packing were done under general anesthesia resulting in cessation of bleeding. CONCLUSIONS: High-pressure water douche is recognized as producing serious vaginal injury in adult women but is not well reported as a cause of genital trauma in the pediatric population. Although not well documented, the prepubescent vagina is capable of receiving significant trauma due to highly pressurized water. Initial trauma management should be implemented with subsequent repair of the laceration, if possible. The prepubescent genital anatomy must be taken into account during examination and postoperative care. PMID- 17351413 TI - Novel applications of ultrasound in pediatric emergency medicine. AB - A new field, termed emergency ultrasound (EUS), has recently been established. The past decade saw rapid development in the field of EUS in adult patients, especially as performed by emergency medicine physicians. Ultrasound imaging offers several advantages over traditional radiographic techniques, many of which are especially relevant to patients in the pediatric emergency department. Recent literature has documented increased use of EUS for pediatric patients. This review will examine basic principles of ultrasound relevant to pediatric emergency medicine physicians. Emphasis will be placed on understanding the instrument and its limitations. In addition, we will review recent developments in this field. It is our goal that the reader will gain an understanding of the strengths and limitations of this instrument and will therefore be in a position to plan their own program in EUS in pediatrics. Furthermore, it is hoped that this review will serve as an impetus for innovative research, to refine and extend the indications of this modality to benefit patients in the pediatric emergency department. PMID- 17351415 TI - ECGs in the ED. PMID- 17351416 TI - Acute liver failure in children. AB - OBJECTIVE: To review the incidence, etiologies, pathophysiology, and treatment of acute liver failure (ALF) in children. Emphasis will be placed on the initial management of the multiple organ system involvement of ALF. METHOD: MEDLINE search from 1970 to March 2005 was performed. Search headings were as follows: acute liver failure, fulminant liver failure, pediatric liver failure, hepatic encephalopathy, and liver transplantation. Studies written in English were selected. Pediatric studies were emphasized. Adult studies were referenced if there were no pediatric studies available in regard to a specific aspect of liver failure. CONCLUSIONS: Pediatric acute liver failure is a rare but life threatening disease. The common etiologies differ for given age groups. Management includes treating specific causes and supporting multiple organ system failure. Commonly associated disorders that require initial recognition and treatment include energy production deficiencies (hypoglycemia), coagulation abnormalities, immune system dysfunctions, encephalopathy, and cerebral edema. Criteria used to determine the need for liver transplant are reviewed as well as the difficulties associated with predicting which patients will meet these criteria and how rapidly liver transplant will become the only option. Finally, experimental procedures that may provide additional time for the liver to recover are briefly reported. PMID- 17351417 TI - Automated evaluation of sensitivity to foot shock in mice: inbred strain differences and pharmacological validation. AB - Assessing foot shock sensitivity in rodents can be useful in identifying analgesic or hyperalgesic drugs, and phenotyping inbred or genetically altered mice. Furthermore, as foot shock is an integral part of several rodent behavioral models, sensitivity should also be assessed to accurately interpret behavioral measures from these models. To eliminate variability and increase the efficiency of manually scored shock sensitivity paradigms, we utilized a startle reflex system to automatically quantify responses to varying levels of foot shock. Eight inbred mouse strains were tested for reactivity to foot shock in this system, as well as inherent startle response activity to loud noise bursts. Strain rank order for shock reactivity differed from that for acoustic startle, suggesting that pathways activated in response to each differed. Analgesic doses of morphine and acetaminophen specifically reduced foot shock responses without affecting motor reflexive responses to loud noises in each strain tested. We also tested diazepam and scopolamine, which are often used to disrupt behavior in shock related paradigms to illustrate the usefulness of this assay. Overall, these results demonstrate that our automated method is a quick and simple way to accurately assess potential foot shock sensitivity differences owing to strain, genotype or drug treatments. PMID- 17351418 TI - Pharmacological profiles in rats of novel antipsychotics with combined dopamine D2/serotonin 5-HT1A activity: comparison with typical and atypical conventional antipsychotics. AB - Combining antagonist/partial agonist activity at dopamine D2 and agonist activity at serotonin 5-HT1A receptors is one of the approaches that has recently been chosen to develop new generation antipsychotics, including bifeprunox, SSR181507 and SLV313. There have been, however, few comparative data on their pharmacological profiles. Here, we have directly compared a wide array of these novel dopamine D2/5-HT1A and conventional antipsychotics in rat models predictive of antipsychotic activity. Potency of antipsychotics to antagonize conditioned avoidance, methylphenidate-induced behaviour and D-amphetamine-induced hyperlocomotion correlated with their affinity at dopamine D2 receptors. Potency against ketamine-induced hyperlocomotion was independent of affinity at dopamine D2 or 5-HT1A receptors. Propensity to induce catalepsy, predictive of occurrence of extrapyramidal side effects, was inversely related to affinity at 5-HT1A receptors. As a result, preferential D2/5-HT1A antipsychotics displayed a large separation between doses producing 'antipsychotic-like' vs. cataleptogenic actions. These data support the contention that 5-HT1A receptor activation greatly reduces or prevents the cataleptogenic potential of novel antipsychotics. They also emphasize that interactions at 5-HT1A and D2 receptors, and the nature of effects (antagonism or partial agonism) at the latter has a profound influence on pharmacological activities, and is likely to affect therapeutic profiles. PMID- 17351419 TI - Effects of amphetamine on differential reinforcement of low rates of responding. AB - A multiple differential reinforcement of low rate 8 s discrete-trial, differential reinforcement of low rate 8 s free-operant procedure was used to investigate the effects of D-amphetamine on interval timing in pigeons. On the discrete trial differential reinforcement of low rate early responses terminated the trial; on the free-operant differential reinforcement of low rate early responses reset the reinforcement timer but had no other effects. Frequency distributions of log interevent times for responses following reinforcement on both the free-operant and discrete-trial components showed a single-peaked distribution. The interevent time distribution for responses preceded by unreinforced responses on the free-operant differential reinforcement of low rate showed two peaks. The pigeons were administered two doses of D-amphetamine for 20 successive sessions. The means of interevent time distributions did not change under drug for either condition but widths of the distributions increased in both conditions and for both types of interevent times in the free-operant differential reinforcement of low rate. In the free-operant condition the mean interevent time for responses preceded by prior responses declined significantly with drug owing to a reduction in the proportion of responses in the shorter interevent time distribution. In effect, response bouts were shortened by drug administration. The rate-dependent hypothesis well described the effect of amphetamine on responses in the free-operant procedure. These results are discussed in the context of amphetamine's effects on the temporal structure of behavior. PMID- 17351420 TI - Chronic administration of clozapine alleviates reversal-learning impairment in isolation-reared rats. AB - Isolation rearing has been used for inducing schizophrenia-like symptoms in rats. Human schizophrenics have deficits in prefrontal-dysfunction-related cognitive/behavioral flexibility. Rats with lesions of the medial prefrontal cortex perform poorly in reversal learning. It is uncertain whether isolation rearing, however, causes reversal-learning impairment in adult rats. Using the rotating T maze, this study examined the effect of chronic administration of clozapine on visual discrimination learning and reversal learning in isolation reared and socially reared adult rats. The results show that isolation-reared rats without clozapine injection performed significantly worse than socially reared rats in reversal learning but not in acquisition learning. Chronic injection of clozapine (5 or 10 mg/kg) in isolation-reared rats significantly improved reversal learning but had no effects on acquisition learning. Further data analyses show that in both the inhibition phase and the new-strategy acquisition phase of reversal learning, isolation-reared rats needed significantly more correct-response trials to reach the criterion than socially reared rats, and clozapine significantly reduced the isolation-induced impairment of reversal learning only in the new-strategy-acquisition phase. In socially reared rats, clozapine had a dose-related interfering effect on reversal learning but not acquisition learning. This study supports the use of isolation rearing as a model for investigating the neurodevelopmental hypothesis of schizophrenia. PMID- 17351421 TI - Reversal of haloperidol-induced extrapyramidal symptoms by buspirone: a time related study. AB - Effects of coadministration of buspirone were investigated on the time course of haloperidol-induced extrapyramidal symptoms in rats. Rats treated with haloperidol at a dose of 1 mg/kg exhibited impaired motor coordination and a decrease in exploratory activity. Coadministration of buspirone at a dose of 1 mg/kg attenuated haloperidol-induced deficits of motor coordination but no effect was produced on the deficits of exploratory activity, possibly because of a 'floor effect'. Long-term administration of haloperidol (1 mg/kg) twice a day for 5 weeks did not produce tolerance to haloperidol-induced deficits of exploratory activity. The deficits of motor coordination were attenuated after 4-5 weeks of drug administration. Coadministration of buspirone for 3-5 weeks attenuated and reversed haloperidol-induced deficits of exploratory activity. Deficits of motor coordination were smaller in rats cotreated with buspirone after 1 week but not after 2-5 weeks. Administration of haloperidol for 2 weeks elicited vacuous chewing movements with twitching of facial musculature that increased in a time dependent manner as the treatment continued to 5 weeks. Animals cotreated with buspirone exhibited a gradual reversal of the response during 2-5 weeks of treatment. The mechanism involved in the attenuation/reversal of haloperidol induced extrapyramidal symptoms by buspirone is discussed. Prior administration of buspirone for 2 weeks may be of help in the improvement of extrapyramidal symptoms induced by antipsychotic drugs. PMID- 17351422 TI - Plasma levels of rotigotine and the reversal of motor deficits in MPTP-treated primates. AB - Rotigotine is a nonergolinic dopamine D3/D2/D1-receptor agonist used clinically for the treatment of Parkinson's disease. This study aimed to determine the relationship between peak antiparkinsonian activity and drug plasma levels after administration of rotigotine to 1-methyl-4-phenyl-1,2,3,6-tetrahydropytidine treated primates. Using single subcutaneous injections of rotigotine and blood sampling at two subsequent time points, the relationship between improvement in motor activity and plasma rotigotine level was evaluated in 1-methyl-4-phenyl 1,2,3,6-tetrahydropytidine-treated common marmosets. Rotigotine (0.01875-0.3 mg/kg subcutaneously) produced an increase in locomotor activity even at the lowest dose tested. Total increase in motor activity and duration of drug effect were dose related. Motor disability was similarly improved by rotigotine in a dose-dependent manner. At the highest doses, hyperactivity and stereotypy were observed. Plasma concentrations of rotigotine were linearly related to dose over dosage range employed, but not to behavioral response. Results show that pulsatile administration of rotigotine effectively normalizes motor activity in 1 methyl-4-phenyl-1,2,3,6-tetrahydropytidine-treated marmosets. Although dose and plasma concentrations of rotigotine are closely related, drug effects in the brain measured as locomotion and improvement of disability dissociate from plasma levels. Plasma levels corresponding to the optimal dose range (0.01875-0.075 mg/kg) will guide a continuous administration regimen of rotigotine in a subsequent study using the same experimental model of Parkinson's disease. PMID- 17351423 TI - Resistance to change of alcohol self-administration: effects of alcohol-delivery rate on disruption by extinction and naltrexone. AB - A common finding in resistance to change research with food-maintained operant behavior is that the persistence of behavior depends on the rate of reinforcement delivered in the context in which the behavior occurs. The present experiment evaluated the effects of rate of response-dependent alcohol delivery on the resistance to change of rats' alcohol self-administration in the face of disruption produced by extinction and a range of doses of naltrexone (1.0, 3.0, 10.0 mg/kg, subcutaneous). Rats responded for a 10% alcohol solution in a multiple schedule of reinforcement arranging a higher rate of alcohol delivery (variable interval 15 s) in the presence of one stimulus and a lower rate of alcohol delivery (variable interval 45 s) in the presence of another stimulus. Baseline response rates and resistance to extinction were higher in the presence of the stimulus associated with higher rates of alcohol delivery. This finding is consistent with studies of the resistance to change of food-maintained behavior. The rate of alcohol delivered in the components, however, did not systematically affect resistance to disruption by naltrexone. One interpretation of this finding from the perspective of behavioral momentum theory is that naltrexone may decrease the impact of alcohol-associated stimuli on the persistence of drinking by reducing sensitivity to the relative reinforcement conditions arranged in the presence of different stimuli. PMID- 17351424 TI - Fixed-ratio schedules of cocaine self-administration in rhesus monkeys: joint control of responding by past and upcoming doses. AB - By manipulating a signaled upcoming cocaine dose, we investigated how the dose just received and the upcoming dose jointly controlled cocaine self administration. Three rhesus monkeys self-administered cocaine according to a multiple schedule differing in dose following completion of a fixed-ratio response requirement. The larger dose (0.03 or 0.056 mg/kg) was 10-fold higher than the smaller dose (0.003 or 0.0056 mg/kg). Following each infusion, there was an equal probability that the next dose would be large or small. This resulted in four types of signaled transitions: from a small dose to a small dose, small to large, large to large, and large to small. Across conditions the response requirement was increased. At lower ratios, pauses were brief and run rates were controlled by the upcoming dose. At larger ratios, pauses were pronounced, and run rates suppressed, in transitions from a large to a small dose. The behavioral disruption engendered by this transition occurred with both dose combinations. The results suggest that negative discriminable shifts in drug availability disrupt ongoing responding. PMID- 17351426 TI - In vitro evaluation of magnetic resonance imaging at 3.0 tesla on clonogenic ability, proliferation, and cell cycle in human embryonic lung fibroblasts. AB - OBJECTIVES: We investigated the influence of magnetic resonance (MR) at 3.0 T on clonogenic ability, proliferation, and cell cycle in an embryonic human cell line. MATERIALS AND METHODS: Cells (human lung fibroblasts Hel 299) were exposed to the static magnetic field (3.0 T) of a magnetic resonance imager (MRI) and to a turbo spin echo sequence at 3.0 T within clinical limitations (specific absorption rate 0.92 W/kg). A special MR-compatible incubation system was used. A control group (sham-exposed) and a MRI group (exposed) were set up. We investigated 3 biologic endpoints: colony forming, cell cycle, and proliferation ability. The exposure time was 2 hours in each experiment. RESULTS: In the statistical analysis, none of these tests showed relevant differences between the exposed and sham-exposed group. CONCLUSIONS: No influences of the static field alone as well as a turbo spin echo sequence at 3.0 T on clonogenic ability, proliferation, or cell cycle in eugenic human lung fibroblasts were found. PMID- 17351427 TI - Proton magnetic resonance spectroscopic imaging in the border zone of gliomas: correlation of metabolic and histological changes at low tumor infiltration- initial results. AB - PURPOSE: We sought to retrospectively investigate differences in correlation of absolute metabolites concentrations and metabolite ratios with histopathologic parameters of stereotactic biopsies from the border zone of gliomas. MATERIALS AND METHODS: Proton magnetic resonance spectroscopic imaging (H-MRSI) with high spatial resolution was performed in 10 glioma patients at 1.5 T. Magnetic resonance spectroscopic imaging (MRSI) data were coregistered to a 3D MR data set used for stereotactic procedures. Metabolite concentrations of choline-containing compounds (Cho), creatine (Cr), and total N-acetyl-aspartate (tNAA) in addition to metabolite ratios of Cho/Cr, tNAA/Cr, and Cho/tNAA were calculated for voxel positions at biopsy loci with low tumor cell infiltration. Metabolite values were correlated with histopathologic findings expressed as a relative (% tumor infiltration, %TI) and an absolute parameter (tumor cell number, TCN). RESULTS: We found a strong negative linear correlation for tNAA with %TI (R = -0.773, P < 0.001) and TCN (R = -0.769, P < 0.001) but no correlation for Cho (P > 0.05). On the other hand, the metabolite ratio of Cho/Cr showed a moderate positive linear correlation with %TI (R = 0.523, P = 0.012) and TCN (R = 0.486, P = 0.019), but no correlation was obtained for tNAA/Cr (P > 0.05). Differences in correlation between tNAA and Cho as well as tNAA/Cr and Cho/Cr were significant for both %TI (P = 0.012 and P = 0.024) and TCN (P = 0.016 and P = 0.040) using a t test. CONCLUSIONS: We conclude that absolute values of tNAA are more significant than Cho in the detection of low tumor cell infiltration. On the basis of absolute metabolite values, neuronal damage seems to be more distinct than cell membrane proliferation in the border zone of gliomas. Furthermore, the calculation of metabolite ratios versus Cr for the border zone may yield to misleading results because Cr is not constant in this area. PMID- 17351428 TI - Assessment of hepatic perfusion in transplanted livers by pharmacokinetic analysis of dynamic magnetic resonance measurements. AB - OBJECTIVE: The purpose of this study was to validate the assessment of hepatic perfusion by pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance image series. MATERIALS AND METHODS: Dynamic measurements were performed with a saturation recovery turbo fast low angle shot (ie, FLASH) sequence over the course of approximately 4 minutes in 17 patients with transplanted livers. By pharmacokinetic analysis using an open 2-compartment model, we estimated and correlated an amplitude of signal enhancement, A, and the perfusion rate, kp, with invasive perfusion measurements from implanted thermo diffusion probes (FTDP). RESULTS: Data analysis for segment IV of the transplanted livers yielded a mean blood flow of 81 +/- 19 mL/min/100g and a mean perfusion rate of 13 +/- 6 minutes. There was a significant correlation between FTDP and kp (rS = 0.64, P = 0.01) but not with A. CONCLUSIONS: Although our open 2-compartment model oversimplifies the complexity of hepatic perfusion, it allows a numerically robust estimation of regional blood flow per unit of blood volume. Thus, dynamic magnetic resonance imaging represents a noninvasive method to assess hepatic perfusion rate which can be visualized in color coded images. PMID- 17351429 TI - Evaluation of a reduced dose protocol for respiratory gated lung computed tomography in an animal model. AB - OBJECTIVE: We sought to evaluate and validate a low-dose protocol for respiratory gated multislice computed tomography (CT) for volume calculations in small ventilated neonatal animals as a model for the ventilated human neonatal lung. MATERIALS AND METHODS: Five mechanically ventilated newborn piglets were imaged in a multislice CT scanner (0.5-mm slice thickness, 4:16 pitch, 0.5 seconds rotation time, 120 kV) using a normal (100 mAs) and a reduced (10 mAs) dose protocol. All animals were scanned twice (at 100 and 10 mAs) at each of 3 different ventilator settings. Complete volume datasets were reconstructed throughout the respiratory cycle in increments of 10% using retrospective half scan reconstruction. End-inspiratory volumes and volumes during maximal expiration (functional residual capacity) were calculated by a customized software and values for normal and reduced dose protocols were compared using Kolmogorov-Smirnov test and Bland-Altman plots. RESULTS: Two volume datasets (one normal and one reduced dose protocol) showed artifacts on the axial images, which could not be analyzed by the software. Those values were determined after manual segmentation and excluded from final analysis. The mean (+/-SD) end-inspiratory volumes and functional residual capacity were 34.3 +/- 10.1 mL and 25.3 +/- 8.0 mL for the normal-dose protocol versus 33.1 +/- 10.0 mL and 24.7 +/- 8.1 mL for the reduced-dose protocol, respectively. There was no statistically significant difference between normal and reduced dose protocol (KS-Test: D = 0.14 < Dmax). CONCLUSION: Lung volume calculation in ventilated newborn piglets (end inspiratory volumes and functional residual capacity) can be performed using respiratory-gated multislice CT even at a substantially reduced dose (eg, to 10 mAs). This makes the technique a candidate for future pediatric use. PMID- 17351430 TI - Fluorescent bacterial magnetic nanoparticles as bimodal contrast agents. AB - OBJECTIVES: The purpose of this study was to assess whether fluorochrome-coupled bacterial magnetic nanoparticles can be used as bimodal contrast agent for both magnetic resonance imaging (MRI) and near-infrared fluorescence optical (NIRF) imaging of cultured macrophages. MATERIALS AND METHODS: Bacterial magnetic nanoparticles (magnetosomes, particle diameter: 42 nm) were harvested from Magnetospirillum gryphiswaldense and characterized by using MRI. After covalent coupling to the fluorescent dye DY-676 (lambdaabs./lambdaem.= 676 nm/701 nm, Dyomics, Jena, Germany), the fluorescent magnetosomes were analyzed by fluorescence-activated cell sorting. Subsequently, murine macrophages J774 were incubated with the bimodal contrast agent (3 hours) and examined by a whole-body near infrared small animal imaging system as well as by using a 1.5 T clinical MR system. Moreover, labeled cells were characterized using confocal laser scanning microscopy (CLSM) and ultrathin section transmission electron microscopy. RESULTS: Characterization of the nanoparticles by MRI revealed R1 and R2 relaxivities of 3.2 mMs and 526 mMs, respectively. Fluorochrome-coupled magnetosomes exhibited increased fluorescence intensities at wavelengths >670 nm. Macrophages that were incubated with the contrast agent showed a significant fluorescence emission in the near infrared range as imaged with a whole body NIR imaging system, FACS analysis and CLSM. Moreover, CLSM data showed the greatest fluorescence intensities within intracellular compartments and colocalized with the magnetosomes. With MRI, both T1 and T2 relaxation times were substantially shortened at concentrations greater than 600 cells/microL. DISCUSSION AND CONCLUSION: Macrophages could be labeled with fluorescent magnetosomes, and they were successfully imaged using both a 1.5 T MR scanner as well as with NIRF optical methods. The use of this bimodal contrast agent for diagnostic purposes may benefit from the excellent spatial resolution of the MRI and the high sensitivity of the fluorescence imaging. PMID- 17351431 TI - Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging. AB - RATIONALE AND OBJECTIVES: To investigate the potential of gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for the differential diagnosis of nonalcoholic steatohepatitis (NASH) and fatty liver (FL). METHODS: Twenty-one male rats were divided into 3 groups. Seven rats in the NASH group were fed a choline-deficient diet for 10 weeks, and the 7 rats in the FL group were fed a standard diet also containing 1% (wt/wt) orotic acid for 4 weeks. As a control, 7 rats were fed a standard diet. After the feeding period, all rats were subjected to contrast-enhanced dynamic and delayed MRI with a 2D-FLASH technique. Gd-DTPA (0.1 mmol Gd/kg) and Gd-EOB-DTPA (0.025 mmol Gd/kg) were injected into the tail vein at 24-hour intervals. Signal intensities of the liver were measured for each MR image and the relative enhancement (RE) was calculated. In addition, the time of maximum RE (Tmax) and the half-life of RE (T1/2) in liver were compared. After MRI, the liver was histologically analyzed to evaluate steatosis, hepatitis, and fibrosis. RESULTS: Diffuse macrovesicular steatosis and severe fibrosis were observed in the NASH group, whereas diffuse microvesicular steatosis and rare fibrosis were observed in the FL group. Immediately after the Gd-DTPA injection, the RE in the liver of each group temporarily increased, and thereafter, rapid RE reduction was observed. However, a continuous increase and subsequent slow reduction of RE were induced after the Gd-EOB-DTPA injection. Although there was no difference between the Tmax and T1/2 of each group after the Gd-DTPA injection, Tmax and T1/2 of the NASH group were significantly prolonged in comparison with FL and control groups after the Gd-EOB-DTPA injection (P < 0.01). CONCLUSIONS: It was possible to differentiate NASH and FL by evaluating the SI time course on Gd-EOB-DTPA enhanced MRI. PMID- 17351432 TI - Improved evaluation of myocardial perfusion and viability with the magnetic resonance blood pool contrast agent p792 in a nonreperfused porcine infarction model. AB - OBJECTIVES: To investigate whether a magnetic resonance (MR) blood pool contrast agent enables both evaluation of myocardial perfusion and viability in nonreperfused infarction in pigs. MATERIALS AND METHODS: An optimized MR protocol using the blood pool contrast agent P792 (0.026 mmol/kg, twice the clinical dose, Guerbet, France) was investigated to evaluate nonreperfused myocardial infarction in an animal model. P792 was compared with the extracellular contrast agent Gd DOTA (0.1 mmol/kg). The MRI findings were compared with histomorphometry performed with microspheres to evaluate perfusion and triphenyltetrazolium chloride (TTC) to evaluate viability. Contrast-enhanced MR imaging of the heart was performed on a 1.5-Tesla scanner 2 days after instrumentation in 6 minipigs. A saturation recovery steady-state free precession sequence was used for perfusion imaging and an inversion recovery fast low-angle shot sequence for evaluation of myocardial viability. RESULTS: P792 tended to depict areas of reduced perfusion more accurately than Gd-DOTA (17.2% +/- 11.1% versus 13.7% +/- 8.0%) in comparison to the gold standard of histomorphometry with microspheres (18.2% +/- 9.8%). Moreover, P792, but not Gd-DOTA, depicted ischemic areas for 30 minutes after intravenous injection. The change in myocardial signal intensity during first pass was not significantly different after P792 compared with Gd DOTA (140.3% +/- 64.4% versus 123.3% +/- 22.5%, P = 0.56). P792 was highly accurate in depicting infarcted areas (11.1% +/- 7.1%) compared with Gd-DOTA (12.1% +/- 8.2%, r = 0.98, P < 0.001) and histomorphometry with TTC (12.2% +/- 8.0%, r = 0.99, P < 0.001). CONCLUSIONS: Unlike Gd-DOTA, the blood pool contrast agent P792 allows evaluation of myocardial perfusion for a period of 30 minutes and shows good agreement with histomorphometry. P792 must be examined in further studies to evaluate its potential in evaluating early myocardial lesions and reperfusion. In addition, P792 also allows for evaluation of myocardial viability. PMID- 17351433 TI - Dynamic magnetic resonance nephrography: is saturation recovery TrueFISP advantageous over saturation recovery TurboFLASH? AB - PURPOSE: In this volunteer study, 2 navigator-gated strongly T1-weighted saturation-recovery (SR) sequences, a turbo fast low angle shot (TurboFLASH) and a new true fast imaging in steady precession (TrueFISP) readout technique, were compared for suitability in dynamic magnetic resonance nephrography. MATERIALS AND METHODS: Ten healthy volunteers (mean age 26.1 +/- 3.6) were equally divided into 2 subgroups. After bolus-injection of 3.75 mL of gadobutrol (approximately 0.05 mmol/kg body weight), slightly obliqued coronal single-slice images of the kidneys were recorded every 4-5 seconds during free breathing using 1 of the 2 sequences. Time-intensity curves were determined from manually drawn regions-of interest over the kidney parenchyma. Both sequences were subsequently evaluated with regard to linearity of signal, signal to noise ratio (SNR), and time dependent behavior of signal intensity curves. RESULTS: : The TurboFLASH readout showed better linearity of the signal behavior as compared with the TrueFISP technique (TurboFLASH: no deviation from linearity down to T1 = 400 milliseconds; TrueFISP at T1 = 700 milliseconds: 12% deviation, at T1 = 400 milliseconds: 19%). The time-intensity curves of the TrueFISP sequence exhibited distinctly lower variability than the TurboFLASH approach. The SNR increased with TrueFISP by 3.4 +/- 0.5-fold for native renal parenchyma and by 3.3 +/- 0.9 for contrast-enhanced renal parenchyma. For split renal function evaluation, the linear regression to the signal increase in the first minutes after the first pass could be performed with higher reliability using the TrueFISP technique (increase of correlation coefficient by 17.1%). CONCLUSION: A SR navigator-gated TrueFISP sequence seems most favorable for dynamic magnetic resonance nephrography due to the high signal yield and low curve variability. PMID- 17351434 TI - Searching for alleles associated with complicated outcomes after burn injury. AB - Sepsis is a serious and growing health problem among patients admitted to intensive care units. When accompanied by organ failure, sepsis carries a 30-50% case-fatality rate. Although our understanding of burn pathophysiology has grown in recent years, we are still unable to identify accurately patients who are at increased risk for infectious complications and death. Genetic predisposition is likely to explain a portion of this variation. Understanding which genes and allelic variants contribute to disease risk would increase our ability to predict who is at increased risk and intervene accordingly, as well as identify molecular targets for novel and individualized therapies. Several obstacles exist to identification of which specific alleles and loci contribute to patient risk, including achievement of sufficient statistical power, population admixture and epistatic interaction among multiple genes and environmental factors. Although increasing sample size will resolve most, if not all, of these issues, slow patient accrual often makes this solution impractical for a single institution within a reasonable timeframe. This situation is complicated by the fact that traditional analysis methods perform poorly in the face of data sparseness. Identification of risk factors for severe sepsis and death after burn injury will likely require collaborative patient enrollment as well as development of advanced analytical methodologies. While overcoming these obstacles may prove difficult, the effort is warranted, as the ultimate benefit to patients is considerable. PMID- 17351435 TI - Management of postburn contractures of the upper extremity. AB - Postburn contractures of the upper extremity are better prevented than treated, but many patients still suffer from this disability, especially after suboptimal primary care or major burns. Principles applicable to release of postburn contractures of the upper extremity are discussed, with a joint-specific review of relevant techniques to accomplish the release of the contracture. Pre- and postoperative care is discussed. PMID- 17351436 TI - How patients enter the burn care system is changing: a glimmer from the National Burn Repository. PMID- 17351438 TI - The relationship of serum lactate and base deficit in burn patients to mortality. AB - Serum lactate and base deficit in trauma patients have been shown to correlate with mortality. This study examines the relationship of these parameters to mortality among burn patients. We evaluated patients with >or=20% TBSA burn injury who had a serum lactate or base deficit recorded during the initial 48 hours of admission over a 5-year period. The primary study outcome was mortality. The mean (+/-SD) age of study patients (N = 128) was 35.2 +/- 21.1 years, the mean burn size was 41.7 +/- 17.9% TBSA, and the mortality rate was 17.1%. Mean serum lactate values of patients who died were significantly higher than those of survivors at admission and at 12, 18, and 24 hours after admission. The highest serum lactate value in the first 48 hours after admission was higher for nonsurvivors than survivors. Mean base deficit at admission and 6 hours after admission was significantly lower in patients who died than in survivors; in addition, the worst base deficit during the first 48 hours of care was significantly lower in patients who died than in those who survived. Early serum lactate and base deficit values are often worse for burn patients who die than for survivors. Elevation of serum lactate values during the first 48 hours after a burn is an independent risk factor for death, but no threshold value for serum lactate is demonstrable. Resuscitation should not be withheld from burn patients on the basis of any lactate or base deficit value. PMID- 17351437 TI - Standard operating procedures for the clinical management of patients enrolled in a prospective study of Inflammation and the Host Response to Thermal Injury. AB - As part of the National Institutes of General Medical Sciences (NIGMS)-funded Inflammation and the Host Response to Injury study, participating investigators created a database, a clinical data collection protocol, and web-based case report form. To obtain high-quality clinical endpoints for correlation with genomic data, a uniform approach to patient management between centers was required. Standard operating procedures (SOPs) were generated to minimize variability and promote a uniform standard of patient care. The SOPs are necessary to enable validation of the clinical endpoints to be used for comparison with genomic and proteomic information derived from samples of blood and tissue obtained from thermally injured patients. Participating investigators identified areas of potential practice variation and developed a set of SOPs based on available data and sound clinical principles. In the absence of sufficient clinical data to identify a single management strategy, SOPs were designed to apply the best approach to management without interfering with local standards of care. The data- collection instrument, or case report form, was constructed concurrently with the SOPs. Wherever possible, the case report form was modified to collect data that might resolve controversial management issues. Modifications in management strategies that were necessary for children are delineated as needed. Data queries and site visits were conducted to audit compliance. SOPs for 10 areas of clinical care were developed. The institution of the SOPs required minor changes in clinical practice patterns and personnel training but did not require participating centers to procure new technology or alter the utilization of clinical resources significantly. The SOPs represent current management strategies applied to the study population to reduce variation in patient management. The SOPs are easily adaptable to other burn-related clinical protocols as well as to the routine daily management burn patients. PMID- 17351439 TI - Pneumonia after inhalation injury. AB - We sought to evaluate the incidence, morbidity, and mortality of pneumonia among inhalation injury patients requiring admission to our burn unit. We undertook a retrospective study of 228 consecutive patients with inhalation injury who were admitted to the burn unit of a level one trauma center between 2001 and 2004. Of the remaining 117 patients with inhalation injury and requiring hospitalization for at least 48 hours, 32 (27%) developed pneumonia. The average patient with inhalation injury and pneumonia developed their infiltrate on day 6 +/- 5 days and required 3 +/- 4 burn operations. There was no difference seen in age, sex, or carboxyhemoglobin level between inhalation injury patients with and without pneumonia (P > .05). The inhalation injury patients that had an associated TBSA burn of at least 20% had a 60% (12/20) pneumonia rate, which was significantly higher then the 21% (20/97) pneumonia rate observed in patients with an association burn less then 20%. The overall mortality of patients with inhalation injury and pneumonia was 19% (6/32), double the mortality rate of 9% (8/85) found in patients with inhalation injury and no pneumonia. The average length of stay of inhalation injury patients with pneumonia was significantly longer (47 +/- 44 days) then inhalation injury patients without pneumonia (26 +/- 54 days; P < .05). The presence of pneumonia among inhalation injury patients significantly increased length of stay and doubled mortality rates. Admission carboxyhemoglobin levels, age, and sex had no relationship to the development of pneumonia. An increase in TBSA burn was associated with a higher pneumonia rate. PMID- 17351440 TI - Invited critique: fostering a plurality of voices in the burn literature: a concept not common to scholarly consideration of the editorial peer review process. PMID- 17351441 TI - Outcomes of Acinetobacter baumannii infection in critically ill burned patients. AB - The objective of this study was to determine the incidence of drug resistance among isolates of Acinetobacter baumannii from our Burn Intensive Care Unit (BICU), the rate of clinical cure, and the mortality rate. We undertook a retrospective review of all cases of infection from the BICU between January 2004 and November 2005. The group consisted of 24 men (80%) and 6 women with a mean age of 43 years (range, 17-76 years, +/-14.5 years). Mean TBSA burned was 43% (range, 9-75%, +/-19%). Mean BICU length of stay was 49 days (range, 5-118 days, +/-30 days). Patients developed their first infection after a mean of 16 days (5 73 days, +/-14 days). The initial site of infection was bronchoalveolar lavage in 21 (70%), blood in 6 (20%), central venous catheter tip in 2 (7%), and urine in 1 (3%). The isolates displayed resistance to imipenem in 87% of cases. No organism displayed resistance to colistin (polymixin E). Patients were treated with colistin in 20 cases (67%), with amikacin in 8 cases (27%), and with imipenem in 2 cases (7%). A total of 10 patients (33%) died, 1 from gastrointestinal bleeding and 9 from active infection, giving an infection related mortality of 30%. In 21 cases (70%), a cure was achieved with a mean duration of treatment of 16 days (range, 4-30 days, +/-7 days). The majority of A. baumannii isolates were multidrug resistant; however, no isolate displayed resistance to colistin. Cure rate was 70% and infection-related mortality reached 30%. More investigation is warranted to improve prevention and to assess new therapeutic agents. PMID- 17351442 TI - Electrical and lightning injuries. AB - The aim of this study was to explore the mechanisms, complications, morbidity, and mortality associated with electrical injuries. Of 5053 acute burn admissions during a 5-year period, 202 patients (4%) had electrical burn injuries. Their mean age was 27.5 years (range, 3-71 years). Ninety-eight percent were male, and the extent of burn ranged from 1% to 70% TBSA (mean, 10.5 +/- 10.7% TBSA). High voltage electricity caused 54% of the electrical injuries. Forty-two percent were caused by low-voltage currents and 4% by lightning. A total of 217 surgical procedures were performed on 202 patients Fifteen patients (7.4%) required amputation. All patients who had abnormal electrocardiograms underwent cardiac monitoring. Four had cardiac complications. Mean hospital stay was 13.9 +/- 14.6 days (range, 1-90). Four patients (2%) died. Electrical burn injuries continue to be a serious problem of modern society. Climbing power poles is the most common mechanism for high-voltage injury. Special consideration is required to prevent this type of injury in our region. PMID- 17351443 TI - Growth deceleration and restoration after serious burn injury. AB - There is a common perception that burned children are at risk for growth deceleration. However, because the prevalence, duration, and degree of this stereotypic growth are poorly described, making informed decisions about treatment is difficult. This article describes the natural history of growth after burn injury, according to the findings of a retrospective review conducted in a regional pediatric burn center. The study population comprised children younger than 13 years at the time of injury, who survived burns involving >or=30% TBSA. Main outcome measures were height and weight; values obtained upon admission for burn injury and at all subsequent hospital admissions were converted to height-for-age and weight-for-age Z scores with use of a reference standard. Z scores were then used to determine whether baseline height and weight status (according to initial admission data) were recouped after burn injury. Medical records of 159 patients (2910 admissions) were reviewed. Children with massive burns (>or=50% TBSA) had height-for-age Z scores that were significantly below their baseline average for all years studied (mean fall in Z score units of 0.50-0.76; P < .0001). This decline in height-for-age Z scores represented a deficit of 1.6 to 5.8 cm. Seventeen patients (11%) had height-for-age Z scores consistent with stunting. Weight-for-age Z scores were not statistically lower than the reference standard, except for patients with massive burns up to 1.5 years post-burn. In our population of burned children, only massively burned children demonstrated a decline in stature. The decline for most was modest. PMID- 17351444 TI - The use of Hyalomatrix PA in the treatment of deep partial-thickness burns. AB - Since 2001, Hyalomatrix PA (Fidia Advanced Biopolymers, Abano Terme, Italy) has been used in our center on pediatric burned patients as a temporary dermal substitute to cover deep partial-thickness burns after dermabrasion. This "bridge" treatment was adopted to remove necrotic debris (dermabrasion) and to stimulate regeneration in a humid and protected environment (Hyalomatrix PA). We present results obtained with this approach. On the third to fifth day after admission, dermabrasion was practiced on deep burned areas, which were covered with Hyalomatrix PA. Change of dressings was performed every 7 days. On day 21, those areas still without signs of recovery were removed with classic escharectomy and covered with thin skin grafts. We treated 300 patients. Sixty one percent needed only one dermabrasion treatment, 22.3% (67 patients) more than one, and 16.7% (50 patients) the classic escharectomy. A total of 83% of patients healed within 21 days. Our study suggests that the combination of dermabrasion with a temporary dermal substitute could be a good and feasible approach for treatment of deep partial-thickness burns. Prospective randomized studies are now necessary to compare our protocol with the gold standard treatment of topical dressings. PMID- 17351445 TI - Noninvasive methods for determining lesion depth from vesicant exposure. AB - Before sulfur mustard (HD) injuries can be effectively treated, assessment of lesion depth must occur. Accurate depth assessment is important because it dictates how aggressive treatment needs to be to minimize or prevent cosmetic and functional deficits. Depth of injury typically is assessed by physical examination. Diagnosing very superficial and very deep lesions is relatively easy for the experienced burn surgeon. Lesions of intermediate depth, however, are often problematic in determining the need for grafting. This study was a preliminary evaluation of two noninvasive bioengineering methodologies, laser Doppler perfusion imaging (LDPI) and indocyanine green fluorescence imaging (ICGFI), to determine their ability to accurately diagnose depth of sulfur mustard lesions in a weanling swine model. Histological evaluation was used to assess the accuracy of the imaging techniques in determining burn depth. Six female weanling swine (8-12 kg) were exposed to 400 microl of neat sulfur mustard on six ventral sites for 2, 8, 30, or 60 minutes. This exposure regimen produced lesions of varying depths from superficial to deep dermal. Evaluations of lesion depth using the bioengineering techniques were conducted at 24, 48, and 72 hours after exposure. After euthanasia at 72 hours after exposure, skin biopsies were taken from each site and processed for routine hematoxylin and eosin histological evaluation to determine the true depth of the lesion. Results demonstrated that LDPI and ICGFI were useful tools to characterize skin perfusion and provided a good estimate of HD lesion depth. Traditional LDPI and the novel prototype ICGFI instrumentation used in this study produced images of blood flow through skin lesions, which provided a useful assessment of burn depth. LDPI and ICGFI accurately predicted the need for aggressive treatment (30- and 60-minute HD lesions) and nonaggressive treatment (2- and 8-minute HD lesions) for the lesions generated in this study. Histological evaluation confirmed the accuracy of the assessment. The ICGFI instrument offers several advantages over LDPI including real-time blood flow imaging, low cost, small size, portability, and not requiring the patient to be repositioned. A negative, however, is the need for intravenous dye injection. Although this would not be an issue in a hospital, it may be problematic in a mass casualty field setting. Additional experiments are required to determine the exposure time necessary to produce a graded series of partial-thickness HD lesions and to optimize instrumental parameters. The data generated in this follow-on study will allow for a full assessment of the potential LDPI and ICGFI hold for predicting the need for aggressive treatment after HD exposure. The lasting message is that objective imaging techniques can augment the visual judgment of burn depth. PMID- 17351446 TI - The effect of air pressure on edema and healing of scalded tissue of rats. AB - To study the effectiveness of using high-pressure air on edema and healing of second-degree scald burns in rats. A self-designed high pressure airtight box in which the air pressure can be controlled is used to observe the edema and healing time of second degree burned tissues in rat under different air pressures. With the air pressure increased by 30 cm H2O, there was a significant reduction of edema, exudation and healing time of the scalded tissue. Increasing air pressure can reduce edema, exudation and healing time of scalded tissue. PMID- 17351447 TI - The efficacy of linear polarized polychromatic light on burn wound healing: an experimental study on rats. AB - We aimed to investigate the questionable effect of linear polarized polychromatic light on burn wound healing in rats. Two deep second-degree burn wounds on the backside of each of 21 Sprague-Dawley rats were created with a standard burning procedure by applying a heated plaque. Burned regions located right dorsolaterally and classified as group I lesions were treated with linear polarized polychromatic light + open dressing + antibacterial pomade, whereas group II lesions were located left dorsolaterally and treated with only open dressing + antibacterial pomade. Macroscopic evaluation was performed for determination of the completed wound closure rate, measurement of burn wound area, and investigation of macroscopic edema, hyperemia, and epithelialization. Histopathological evaluation included monitoring of epithelialization, vascularization, origination of granulation tissue, inflammatory cell response, and total histopathological score on days 7, 14, and 21 after burn creation. Macroscopic evaluation revealed more obvious epithelialization in group I lesions between days 6 and 15. The number of completely closed wounds was higher in group I than in group II on days 16 and 21. The average area of burn wounds was lower from day 5, hyperemia was less on days 2 to 17, and edema was less from day 4 to day 13 in group I lesions. Histopathological evaluation revealed a higher rate of epithelialization on day 7 and higher vascularization occurrence on day 21 in group I lesions. Linear polarized polychromatic light seems to be effective in the treatment of burn wounds and in the promotion of healing. This may be related to linear polarized polychromatic light stimulation of epithelialization and vascularization. PMID- 17351448 TI - Changing pattern of adult burn referrals to a regional burns centre. AB - The National Burn Care Review prompted us to review trends in adult acute admissions to our unit with the intention to implement the guidelines of referral set down in the report. We had recently also adopted a more open admissions policy in keeping with these recommendations. This was achieved by a retrospective casenote analysis with the years 1981, 1991, and 2001 used as reference snapshot years to outline trends. The results showed an increase in the number of patients, a decrease in the depth and extent of burns, a decrease in the number of inpatient days and crude mortality rate. There was also a slight decrease in the age of patients. PMID- 17351449 TI - Invited critique: changing pattern of adult burn referrals to a regional burn center. PMID- 17351450 TI - Epidemiology of suicide by burns in the province of Isfahan, Iran. AB - The aim of the study was to determine epidemiologic features and factors associated with suicidal behaviors by burns requiring hospitalization in the province of Isfahan, Iran. A prospective population-based study of all suicidal behaviors by burns requiring hospitalization was conducted in the province of Isfahan, Iran, from March 21, 2005 to March 20, 2006. Data were obtained from patients, family members, and/or friends through interviews during the course of hospitalization. A total of 89 patients ages 13 to 62 years with suicidal behaviors by burns were identified during the study period, representing an overall incidence rate of 2.9 per 100,000 persons-year (P-Y; 95% confidence interval 2.3-3.5 per 100,000 P-Y). Females (4.7 per 100,000 P-Y) had a higher rate of suicidal behavior by burns than males (1.2 per 100,000 P-Y; P < .001). The age-specific rate of suicidal behavior by burns peaked at age group 20 to 29 years (6.3 per 100,000 P-Y). Among the population aged 15 to 29 years, married women had a higher rate of suicidal behavior by burns (9.3 per 100,000 P-Y) than single women (6.6 per 100,000 P-Y). The highest rate of suicidal behavior by burns was found among the unemployed population (17.7 per 100,000 P-Y). The most frequent precipitating factor for suicidal behavior was a quarrel with a family member, relative, and/or friend (61.8%). Depression and anxiety disorders were the most frequent psychiatric comorbidities associated with suicidal behaviors. Mortality rate caused by suicidal behavior by burns was 1.4 per 100,000 P-Y. A high rate of suicidal behavior among young and mostly married women in the province of Isfahan is a tragedy and great concern. Social, cultural, and economical factors may contribute to suicidal behavior in Isfahan, and they need to be addressed through education, support, and commitment. Findings of this study can be used for implementation of a preventive program(s) to reduce the incidence of suicide among high risk groups. PMID- 17351451 TI - Dermatology Life Quality Index (DLQI) scores in burn victims after revival. AB - This study aimed to evaluate reliability and validity of the Dermatology Life Quality Index (DLQI) in Iranian burned patients and to examine this question, "Does burn severity or other demographical characteristics affect the patient's perception of his or her quality of life after burn injury?" In this study, we used the Persian version of DLQI questionnaire; its reliability and validity has been confirmed earlier in vitiligo patients. The questionnaire was administered to a group of patients with burn scars after revival. The internal consistency of the questionnaire was assessed by Cronbach's alpha coefficient. Validity was performed using convergent validity. In all, 109 patients (mean age, 28.94) enrolled in the study. The scores of DLQI ranged from 4 to 28 (mean +/- SD, 17.76 +/- 5.55). Reliability analysis showed satisfactory result (Cronbach's alpha, 0.75). Cronbach's alpha coefficient in the patients with a Burn Index >or=15% was greater than those with <15%, which is an acceptable result. The Persian version of the DLQI is a reliable and valid instrument for assessing the impacts of burn scars on quality of life. The life quality index of all the patients irrelevant to age and sex were significantly impaired. PMID- 17351452 TI - Thermal injury in patients with seizure disorders: an opportunity for prevention. AB - Serious burn injuries are a potential threat to patients with seizure disorder. There are limited studies addressing this issue. Therefore, a retrospective study was undertaken with two goals: one to develop better understanding of this potential threat and two to create a prevention message regarding seizure-related burns. The burn center registry was reviewed to ascertain the number of patients who sustained burn injury during or directly after a seizure from 2000 to 2005. Thirty-two patients were admitted (44% female, 56% male) with mean age of 39 years (SD +/- 10.4) after sustaining a burn during or after a seizure. Average TBSA was 8.3% (SD +/- 4.8) with 72% of patients experiencing full-thickness burns. The three most prevalent etiologies were falling into a stove while cooking (34%; n = 11), falling on hot pavement (31%; n = 10), and falling into a campfire (9%; n = 3). A full 88% of patients (n = 28) reported a previous diagnosis of seizure disorder, whereas the other 9% (n = 3) reported seizures related to alcohol consumption. Laboratory reports revealed 20 patients (63%) had subtherapeutic levels of antiseizure medication, 1 patient (3%) had toxic levels, and 5 patients (16%) were not being treated for seizures. Upon discharge, 23 patients went home with family, 5 were discharged to skilled nursing, 1 to a homeless shelter, 1 died, and 2 patients were lost to follow-up. Because of the severe burns observed in epileptic burn patients, a burn-prevention brochure was developed and is being distributed to seizure patients and their families. PMID- 17351453 TI - Therapeutic efficacy of a therapeutic cooking group from the patients' perspective. AB - The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns. PMID- 17351454 TI - Scald prevention campaigns: do they work? AB - The aim of this study was to quantify the effectiveness of the Queensland "Hot Water Burns Like Fire" campaign. Cross-section temperature sampling of households' bathroom hot water taps was conducted in Brisbane in 1990 before the intervention (n = 872) and in 2002 to 2003 after the intervention (n = 871). In both surveys, temperature was measured with thermometers held under running water from the bathroom hot tap until the reading stabilized (2 minutes). In 2002 to 2003 the interviewer also recorded whether or not the householder believed a tempering valve was installed in the home. The main injury outcome measure was all scald injury-related admissions at hospitals in Queensland from July 1990 to June 2003. The difference between the mean hot water tap temperature in 1990 and in 2002 to 2003 was determined with independent sample t-tests (P < .05). Rates of hospital admissions were grouped into two categories: scald injuries per year prior to the introduction of the hot water tempering valve legislation (April 1998) and scald injuries per year post-legislation. The difference between the preintervention and postintervention mean rates was determined with t-tests (P < .05). Additionally, the rates were plotted on a scatter plot by year, and a linear regression analysis was used to quantify the relationship with rates of scald-related injuries and year. The temperature in homes where the occupants reported having a tempering valve (mean = 55.5 degrees C) was significantly lower than in homes whose occupants reported not having a tempering valve (mean = 60.1 degrees C) or did not know whether they had a tempering valve (mean = 61.8 degrees C) (P < .01). However, the comparison of the hot water temperature between 1990 and 2002 to 2003 showed a significantly higher mean hot water temperature in 2002 to 2003 (P < .01). There was a significantly higher mean scald injury rate after the introduction of the "Hot Water Burns Like Fire" campaign (170.36/100,000) than before (113.41/100,000; P = .01). The linear regression line of best fit of these data has a slope of 10.43 (P < .01) and an r of 0.79. The results of this study suggest that the Queensland "Hot Water Burns Like Fire" campaign has not led to a significant reduction in hot water temperature or scald injury rates. The lack of effect identified in this study provides further evidence of the strong need to conduct rigorous evaluations of all major health promotion campaigns to add to the evidence base for such activities. PMID- 17351455 TI - Impact of a pediatric residential burn camp experience on burn survivors' perceptions of self and attitudes regarding the camp community. AB - Summer camp is reported to be a positive and valuable experience for burn and nonburned children. Objective studies comparing the effectiveness, similarities, and differences of rehabilitative vs recreational camps are limited. The aim of this study, year 1, was to assess the effect of burn camp on self-esteem and integration as reported by burn children via the Rosenberg Self-Esteem Scale and a community integration survey. During year 2, burn campers completed these measures again and their self-esteem and integration scores were compared with a group of nonburn campers. The first year results showed significant improvement in burn camper's self-esteem from the beginning to end of camp and successful integration into the camp community. During year 2, burn surviving children reported significantly lower self-esteem before camp than the comparison group, but after camp, burn children's self-esteem was comparable with that of nonburn campers. White non-Hispanic campers reported more sustained improvement in self esteem than other ethnic groups. Burn campers reported a high level of integration into the camp across sex, years since burn, years at camp, or ethnicity, scoring slightly higher than the comparison group. Age was positively correlated with integration among the burn, but not the nonburn campers. Helping children deal with their burn injuries through a rehabilitative program such as burn camp appears to provide benefit for child burn survivors. PMID- 17351456 TI - Metformin-associated lactic acidosis in a burn patient. AB - Hyperglycemia commonly is observed as part of the hypermetabolic response to severe burn injury. In routine burn care, physicians use interventions to address and reduce the complications of this stress-induced hyperglycemia. Metformin (1,1 dimethylbiguanide), an orally administered hyperglycemic medication, has been used previously to modulate the stress-induced hyperglycemic response in nondiabetic burn patients. The use of this medication in nonburn diabetic patients has been associated with the development of lactic acidosis. We present an acute burn patient who developed lactic acidosis while receiving metformin for management of his diabetes. PMID- 17351457 TI - Mobile phone-triggered thermal burns in the presence of supplemental oxygen. AB - In this case report, we present a patient who used a nasal cannula for oxygen supplementation and suffered deep, second-degree burns to his nose and left leg when an electrical spark shot out of the cable's connection socket while the cellular phone was ringing and the cable was, simultaneously, being disconnected from the socket. The cellular phone, a device commonly thought by many people to be both useful and safe, thus has the potential to serve as a heat source that might ignite and cause burns. PMID- 17351458 TI - Acute stroke in the burn patient. AB - A 3-year-old boy was brought to our hospital with 62% TBSA burn injury by boiled water. He received modern burn therapy, including early debridment and skin grafts. The patient discharged 70 days after being burned. Unfortunately, he sustained an acute right-sided hemiparesis 7 days after discharge. Magnetic resonance imaging revealed left middle cerebral artery territory infarction, and a magnetic resonance angiogram showed nonvisualization of left distal intra cranial carotid artery and proximal middle cerebral artery. Thickened walls of these arteries indicated acute dissection. The patient received a follow-up magnetic resonance angiogram study 10 years later to check cerebral vascular lesions that may not have been apparent on the original image studies. It showed only persistently thickened left distal intra-cranial carotid artery and middle cerebral artery walls, indicative of old dissection. Therefore, carotid artery dissection must be considered as one cause of acute stroke in pediatric burn patient, even in the recovery phase of burn injury. PMID- 17351459 TI - Cupping treatment and associated burn risk: a plastic surgeon's perspective. AB - A recent clinical case at the Freiburg University Hospital, Germany, involving burn injuries sustained by cupping treatments is reviewed. The history of the cupping method, indications and contemporary use of this treatment, and the risks from the standpoint of the plastic surgeon are discussed. PMID- 17351460 TI - Superficial burns secondary to misuse of acetic acid solution. AB - Topical use of acetic acid solutions is one of the treatments for human papillomavirus infections, although the disease can spontaneously resolve. Over the-counter availability of acetic acid solutions for medical use presents a potential hazard for misuse. Here we present an example of accidental use. A 13 year-old boy was wounded as a result of using an acetic acid solution for cosmetic purposes. Superficial burns on the left side of his face were managed with topical wound care, and minimal scar formation occurred. PMID- 17351461 TI - Chemical scalp burns after hair highlights. AB - Hair highlighting using chemical solutions to alter the pigmentation of hair is a popular procedure. Given their chemical properties, these solutions also are potentially caustic to the scalp. However, the actual incidence and range of injuries is not well reported in the American literature. We report a representative case from the severe end of the injury spectrum, that of a full thickness chemical burn as a result of direct contact from hair-lightening solution. We review the composition and potential side effects of the chemicals used. Meticulous attention to the instructions of use is recommended to prevent these injuries. To our knowledge, this is the first case report of a full thickness chemical scalp burn as a result of highlighting in the American literature, and we hope that it will serve as an educational resource with respect to the potential risks of this very common procedure. PMID- 17351462 TI - Peer support in the burn center. PMID- 17351465 TI - Induced sputum and exhaled nitric oxide as noninvasive markers of airway inflammation from work exposures. AB - PURPOSE OF REVIEW: Noninvasive measures of airway inflammation are increasingly used in the investigation and management of asthma. Their role in the investigation of occupational lung diseases, however, is not as clearly established. The present article reviews the use of noninvasive methods - induced sputum and exhaled nitric oxide - in the assessment of airway inflammation during the investigation of occupational asthma and eosinophilic bronchitis, and reviews studies investigating the effect of exposure to various occupational agents on airway inflammation in healthy individuals. RECENT FINDINGS: A number of studies have confirmed the association between exposure to occupational agents and the presence of eosinophilic airway inflammation after that exposure in individuals with occupational asthma. Individuals with positive specific inhalation challenges to occupational agents seem to show a greater increase in exhaled nitric oxide than those with negative specific inhalation challenges. Exposure to various agents associated with an increase in exhaled nitric oxide mainly induced a neutrophilic inflammation. SUMMARY: Increasing evidence supports the use of induced sputum as an additional tool in the investigation of occupational asthma. The role of exhaled nitric oxide in the investigation of occupational asthma needs to be clarified due to conflicting evidence reported in the literature. PMID- 17351466 TI - Developments in laboratory diagnostics for isocyanate asthma. AB - PURPOSE OF REVIEW: Isocyanates, reactive chemicals used to generate polyurethane, are a leading cause of occupational asthma worldwide. Workplace exposure is the best-recognized risk factor for disease development, but is challenging to monitor. Clinical diagnosis and differentiation of isocyanates as the cause of asthma can be difficult. The gold-standard test, specific inhalation challenge, is technically and economically demanding, and is thus only available in a few specialized centers in the world. With the increasing use of isocyanates, efficient laboratory tests for isocyanate asthma and exposure are urgently needed. RECENT FINDINGS: The review focuses on literature published in 2005 and 2006. Over 150 articles, identified by searching PubMed using keywords 'diphenylmethane', 'toluene' or 'hexamethylene diisocyanate', were screened for relevance to isocyanate asthma diagnostics. New advances in understanding isocyanate asthma pathogenesis are described, which help improve conventional radioallergosorbent and enzyme-linked immunosorbent assay approaches for measuring isocyanate-specific IgE and IgG. Newer immunoassays, based on cellular responses and discovery science readouts are also in development. SUMMARY: Contemporary laboratory tests that measure isocyanate-specific human IgE and IgG are of utility in diagnosing a subset of workers with isocyanate asthma, and may serve as a biomarker of exposure in a larger proportion of occupationally exposed workers. PMID- 17351467 TI - Work-exacerbated asthma. AB - PURPOSE OF REVIEW: To summarize recent findings on work-exacerbated asthma, based on medical literature published during 2005 and the first 10 months of 2006. RECENT FINDINGS: Although prevalence estimates varied considerably among six recent epidemiologic studies, collectively they contribute to the conclusion that work-exacerbated asthma is common. Median work-exacerbated asthma prevalence estimates were 18% of adults with asthma, 25% of working adults with asthma and 45% of all work-related asthma cases. Work-exacerbated asthma can result from a variety of occupational triggers, including physical factors (e.g. extreme temperatures, exercise), behavioral states (e.g. strong emotions, stress), odors (e.g. perfume), general irritants and dust, and second-hand cigarette smoke. Work exacerbated asthma cases have many of the same demographic and clinical traits as other adults with asthma and occupational asthma cases, although some differences have been reported. Recent review articles have offered some recommendations on the management of work-exacerbated asthma, but more comprehensive advice is anticipated from a professional medical society in the next few years. SUMMARY: Epidemiologic studies indicate that work-exacerbated asthma is common. Researchers have started to pay attention to work-exacerbated asthma, but more studies are needed on all aspects of this condition in order to improve diagnosis, management and prevention. PMID- 17351468 TI - Baker's asthma. AB - PURPOSE OF REVIEW: Baker's asthma is one of the leading causes of occupational asthma and this review describes recent developments in the field. RECENT FINDINGS: The location of bakery production has undergone change and, subsequently, so has the location of baker's asthma. Innovations in the baking industry have also led to new, potentially allergenic, ingredients. A new family of cereal allergens has been identified, including wheat thioredoxin hb (Tri a25). New enzymes are being added to bread that may have allergic potential. The relationship of specific sensitization and baker's asthma has been confirmed in further studies. Measuring specific sensitization to bakery allergens is an essential part of making the diagnosis but there is a lack of standardization of allergen tests. Advancements are being made in the measurement of airborne allergens through the Measurement of Occupational Allergen Exposure project and the development of novel measurement techniques. This will enable better exposure response relationships and more accurate risk assessment. SUMMARY: Progress is being made to better identify bakery allergens and measure exposures accurately. Changes in the location of bread production and new allergens mean that the distribution and determinants of baker's asthma are changing. PMID- 17351469 TI - New insights into laboratory animal exposures and allergic responses. AB - PURPOSE OF REVIEW: To update the epidemiology of laboratory animal allergy, identify new exposures in the laboratory animal workplace, discuss complexities in the exposure-response relationship, and review the immunology of symptomatic and allergic responses. RECENT FINDINGS: Laboratory animal allergy remains a common occupational hazard of research scientists, technicians and animal handlers. The epidemiology is typical of a stable workforce: incidence is low, although prevalence is high. Risk factors of atopy, current exposures, and sensitization to cats or dogs incompletely predict disease. Exposures include a complex, potent mixture of allergens, biological adjuvants such as endotoxin and irritants. The dose-response relationship between laboratory animal exposure, sensitization and symptoms is hard to define: cross-sectional studies identify most sensitized workers in moderate laboratory animal exposure, not in the highest exposure. Exposure assessments based on workday averages underestimate exposure peaks that may be significant for symptoms and disease. Although we have assumed that workers without symptoms are not sensitized to laboratory animal allergens, recent data demonstrate that many asymptomatic workers do make laboratory animal-specific immune responses that may be necessary to prevent symptomatic disease. SUMMARY: Understanding laboratory animal exposures and disease must include exposures other than allergen, and responses other than allergic disease. PMID- 17351471 TI - New developments in the understanding of immunology in silicosis. AB - PURPOSE OF REVIEW: There is compelling evidence that the immune responses induced by crystalline silica particles are implicated in the development of silicosis. This article reviews recent observations which further delineate how innate and adaptive immunity are involved in this lung disease. RECENT FINDINGS: First, silica particles are recognized to have pathogen-associated molecular patterns by the innate immune system. The MARCO receptor expressed on the surface of macrophages appears crucial for the recognition and the uptake of silica as well as the activation of these immune cells in silicosis. Additional data support a major role of inflammation (mast cells, B lymphocytes and TNFalpha) in the development of lung fibrosis but also cancer. Silica-induced acute inflammation is accompanied by thrombosis; strongly suggesting that inhaled silica particles may also induce extrapulmonary lesions. Surprisingly, a pronounced anti inflammatory reaction may also contribute to silica-induced lung fibrosis in mice and represent an additional etiopathogenic pathway of silicosis. Interestingly, it has been proposed that the pulmonary expression of IL-9 (a T lymphocyte related interleukin) or Heme oxygenase-1 (an anti-inflammatory molecule) attenuated silicotic disease progression in animals. SUMMARY: New pathogenic routes involving innate receptors and antiinflammation as well as new antifibrotic immune mediators have been recently described in experimental silicosis, highlighting new potential therapeutic targets and strategies. PMID- 17351470 TI - Flavoring-related bronchiolitis obliterans. AB - PURPOSE OF REVIEW: In 2000, inhalation of butter flavoring vapors was first associated with clinical bronchiolitis obliterans among workers in microwave popcorn production. Toxicologic and epidemiologic studies in the succeeding 5 years have intervention and research implications. RECENT FINDINGS: Irreversible obstructive disease exists in workers throughout the microwave popcorn industry, in flavoring manufacture, and in the chemical synthesis of diacetyl, a predominant chemical in butter flavoring. Biologic plausibility of the role of diacetyl and other components of butter flavoring in causing bronchiolitis obliterans exists in rodent experiments which demonstrate respiratory epithelial necrosis. Some risky jobs were associated with short-term peak flavoring exposures, and average 8-h diacetyl exposures as low as 0.02 parts per million were measured in a work area where disease occurred in workers mixing butter flavorings with heated oil. SUMMARY: Until safe levels of flavoring chemicals are determined, prevention requires substitution, engineering controls, improved work practices, and personal protective equipment to lower exposure, in conjunction with medical surveillance for accelerated declines in pulmonary function. An epidemiologic approach to longitudinal medical surveillance and flavoring chemical exposures, paired with inhalation toxicology studies of flavoring components, will lay the basis for determining health-protective exposure limits for various flavoring chemicals. PMID- 17351472 TI - Prevention of asthma in childhood. AB - PURPOSE OF REVIEW: The prevalence of asthma is increasing in many parts of the world, particularly in developed countries. The present review focuses on recent literature regarding asthma prevention in childhood. RECENT FINDINGS: Several environmental exposures in infancy or early childhood are associated with reduced prevalence of asthma, but the mechanisms leading to these associations remain unknown. Recent studies have demonstrated limited success in the prevention of asthma or asthma symptoms with the use of asthma medications, once the therapy is discontinued. Immunotherapy offers another strategy for asthma prevention, and groups treated with this intervention have demonstrated reduced atopy and asthma. Several multi-interventional trials have demonstrated a reduced asthma symptom burden but have not demonstrated significant differences in objective measures such as lung function or bronchial hyper-responsiveness between intervention groups. SUMMARY: The most promising asthma prevention strategies to date have been those that use a multi-interventional approach employing both dietary and environmental manipulations. More research is needed to assess the long-term follow-up of multi-interventional trials and to evaluate novel intervention strategies in the primary or secondary prevention of asthma in childhood. PMID- 17351473 TI - Management approaches to intermittent wheezing in young children. AB - PURPOSE OF REVIEW: To review the recently published studies addressing various treatment approaches for episodic wheezing in young children. RECENT FINDINGS: A landmark study demonstrated that short courses of oral corticosteroids initiated at the first sign of an upper respiratory tract infection decreased wheezing episode frequency and severity. Since then, alternative treatment strategies have been investigated. Montelukast decreased short-term daytime cough and delayed exacerbations following hospitalization for respiratory syncytial virus bronchiolitis, and led to fewer exacerbations without decreasing oral corticosteroids use among children with intermittent asthma. Preschool children with frequent wheezing at high risk for asthma receiving daily inhaled corticosteroids experienced lower rates of exacerbations requiring oral corticosteroids. Episodic use of inhaled corticosteroids, initiated at the early signs of an upper respiratory infection, led to modest reduction in symptoms, but not oral corticosteroid use. Among young children with 'preasthma', inhaled corticosteroids initiated after 3 days of wheezing did not affect the frequency or severity of wheezing episodes. SUMMARY: Evidence for the preferred treatment strategies for intermittent wheezing in young children remains incomplete. Most of the studies represent heterogeneous populations and lack adequate statistical power to evaluate relevant outcomes. Based on the evidence, there is rationale for further investigation of several management strategies, including corticosteroids and/or leukotriene receptor antagonists administered daily or episodically. PMID- 17351474 TI - Heterogeneity in response to asthma medications. AB - PURPOSE OF REVIEW: Evidence for the heterogeneity of response to asthma medications including inhaled corticosteroids and leukotriene receptor antagonists is mounting. beta2-Adrenoceptor gene polymorphisms may contribute to asthma responsiveness to short- and long-acting beta2-agonists. This review examines recent articles describing variability in response to inhaled corticosteroids, leukotriene receptor antagonists and short-acting beta2-agonists specifically in pediatric persistent asthmatics. RECENT FINDINGS: In the late 1990's, differences in the response to a leukotriene receptor antagonist and an inhaled corticosteroid in adults with moderate persistent asthma were first described. Subsequently, similar findings have recently been elucidated in children with mild to moderate persistent asthma. The variability in response to these two classes of control medicines now appears to encompass all ages with persistent asthma. In general, despite the variability in response to these medications, both resulted in improved clinical and physiologic control measures. SUMMARY: Childhood asthma is a complex disease with numerous clinical phenotypes that contribute to response variability to asthma medications. PMID- 17351475 TI - Difficult to control asthma in children. AB - PURPOSE OF REVIEW: The management of children with difficult asthma requires a systematic approach. These children are prescribed high doses of inhaled or oral corticosteroids and a balance must be struck between therapeutic efficacy and side effects. It is important to ensure the diagnosis is correct and that the reasons for poor control in a given child are characterized so that treatment can be targeted for maximal effect. RECENT FINDINGS: Recent data have demonstrated the correlation between invasive and noninvasive measurement of airway eosinophils. Noninvasive markers of inflammation can be used to determine phenotype and there is increasing evidence on the utility of repeated measures to monitor control and treatment effects. Side effects of high-dose corticosteroids remain a concern. The emergence of new therapies may be of benefit. These are often expensive, however, and have the potential for major side effects. Adherence remains a significant obstacle to the effective management of difficult asthma. SUMMARY: Children with difficult asthma are a heterogeneous group. Characterization and monitoring of these children can be enhanced by measurements of noninvasive markers of inflammation. Further evaluation of new and phenotype specific treatments for children with difficult asthma need to be evaluated in prospective randomized controlled trials. PMID- 17351476 TI - Airway remodelling in children: when does it start? AB - PURPOSE OF REVIEW: The review characterizes airway remodelling in childhood asthma and describes how early in life it is possible to detect, and possibly cure, the cellular and biochemical changes that characterize this event. This topic is timely and relevant since a variety of clinical and epidemiologic studies strongly suggest that in asthma, remodelling may start very early in life and that current prevention and treatment measures, including early avoidance measures and pharmaceutical interventions, are relatively ineffective in preventing the development of irreversible airway changes or in reverting them, once established. RECENT FINDINGS: Recent findings show that structural changes characterizing remodelling, such as subepithelial basement membrane thickening, epithelial cell disruption, protease/antiprotease imbalance and neoangiogenesis, are detectable in children with asthma and even in children with respiratory symptoms or with atopy, before a clear clinical diagnosis of bronchial asthma is made. SUMMARY: Identification of the early structural changes that may precede the development of asthma and of factors leading to permanent loss of lung function appear central to future asthma management. PMID- 17351477 TI - New perspectives in the treatment of allergic rhinitis and asthma in children. AB - PURPOSE OF REVIEW: Allergic rhinitis and asthma are some of the most prevalent chronic diseases in children. Meticulous evaluations of the therapeutic options and interventions are needed to control this burden. The central pathogenic mechanism is an immediate hypersensitivity reaction, followed by interventions in the allergic cascade. Once inflammation is established, potent anti-inflammatory agents or mediator antagonists could help control the phenomenon and reduce the characteristic symptoms related to severity. RECENT FINDINGS: Monoclonal antibody against IgE has demonstrated its efficacy in reducing the symptoms of asthma and rhinitis. In difficult-to-treat asthma patients it allows a reduction in the dose of inhaled steroids, the number of exacerbations, emergency visits and hospitalizations. Its broad implementation is limited by its high cost because adverse events are not a concern. Specific sublingual immunotherapy gave promising results in clinical trials, while modifying immunoglobulins and cytokine profiles, also inducing T-cell tolerance. Safety issues of subcutaneous immunotherapy have been surpassed by the sublingual route, with equivalent efficacy. The new inhaled steroid ciclesonide is effective in established inflammation, is activated only in the respiratory system, and has negligible systemic effects. SUMMARY: Robust evidence on the efficacy and safety of several novel therapies in rhinitis and asthma is available. PMID- 17351480 TI - New potential leads in the biology and treatment of attention deficit hyperactivity disorder. AB - PURPOSE OF REVIEW: This review highlights recent neuroimaging and genetic studies of attention deficit-hyperactivity disorder that may inform biologically targeted interventions and treatments. RECENT FINDINGS: The findings suggest that attention deficit-hyperactivity disorder is characterized by specific learning and cognitive deficits due to abnormalities in dopamine-rich prefrontal circuitry, of genetic or environmental origins. In addition to prefrontal cortical areas, the basal ganglia, cerebellum, and parietal cortex have been implicated in the condition. These regions are part of unique circuits that project both to and from the prefrontal cortex, thus providing a means for signaling prefrontal regions when top-down control of behavior needs to be imposed. Ineffective signaling of control systems by any one of these regions can lead to poor regulation of behavior. Likewise, intact signaling but inefficient top-down control could result in poor regulation of behavior. SUMMARY: Identification of which cognitive and neural processes are altered in attention deficit-hyperactivity disorder and acknowledgement of different casuses of the condition will lead to more individualized, biologically targeted interventions and treatments. This new direction in research and treatment has occurred as the result of a shift from diagnosis as a phenotype, to refined phenotypes of core cognitive deficits that can be more easily tied to the underlying biology. PMID- 17351481 TI - New developments in Smith-Magenis syndrome (del 17p11.2). AB - PURPOSE OF REVIEW: Recent clinical, neuroimaging, sleep, and molecular cytogenetic studies have provided new insights into the mechanisms leading to the Smith-Magenis phenotype and are summarized in this review. RECENT FINDINGS: Cross sectional studies of patients with Smith-Magenis syndrome have found evidence for central and peripheral nervous system abnormalities, neurobehavioral disturbances, and an inverted pattern of melatonin secretion leading to circadian rhythm disturbance. A common chromosome 17p11.2 deletion interval spanning approximately 3.5 Mb is identified in about 70% of individuals with chromosome deletion. Recently heterozygous point mutations in the RAI1 gene within the Smith Magenis syndrome critical region have been reported in Smith-Magenis syndrome patients without detectable deletion by fluorescent in-situ hybridization. Patients with intragenic mutations in RAI1 as well as those with deletions share most but not all aspects of the phenotype. SUMMARY: Findings from molecular cytogenetic analysis suggest that other genes or genetic background may play a role in altering the functional availability of RAI1 for downstream effects. Further research into additional genes in the Smith-Magenis syndrome critical region will help define the role they play in modifying features or severity of the Smith-Magenis syndrome phenotype. More research is needed to translate advances in clinical research into new treatment options to address the sleep and neurobehavioral problems in this disorder. PMID- 17351482 TI - Recent developments in neurofibromatosis type 1. AB - PURPOSE OF REVIEW: This review summarizes the recent clinical and genetic developments in neurofibromatosis type 1 (NF1) and provides an insight into the possible underlying pathomechanisms. RECENT FINDINGS: NF1, or von Recklinghausen disease, is one of the most common hereditary neurocutaneous disorders in humans. Clinically, NF1 is characterized by cafe-au-lait spots, freckling, skin neurofibroma, plexiform neurofibroma, bony defects, Lisch nodules and tumors of the central nervous system. The responsible gene, NF1, encodes a 2818 amino acid protein (neurofibromin). Pathological mutations range from single nucleotide substitutions to large-scale genomic deletions dispersed throughout the gene. In addition to the conventional mutation screening methods, a DNA chip microarray based technology, combinational sequence-based hybridization, has been introduced to expedite mutation detection. Functional analysis has become more amenable following the development of the following: (1) primary Schwann cell cultures from NF1 patients; (2) mouse models; (3) proteomic technologies; and (4) mRNA silencing by RNA interference. These studies have shown that neurofibromin plays a role in adenylate cyclase and AKT-mTOR mediated pathways. It also appears to affect Ras-GTPase activating protein activity through the phosphorylation of protein kinase C which impacts on cell motility by binding with actin in the cytoskeleton. SUMMARY: Recent advances in the clinical features and molecular genetics of NF1 will be discussed together with insights into the underlying pathomechanisms of NF1. PMID- 17351483 TI - Neuroimaging in tuberous sclerosis complex. AB - PURPOSE OF REVIEW: In this review we discuss recent advances in the neuroimaging of patients with tuberous sclerosis complex (TSC), highlighting its application in improving clinical management, particularly in the case of intractable epilepsy. RECENT FINDINGS: Progress in structural and functional imaging has led to further characterization of the brain lesions in TSC. New magnetic resonance imaging techniques that can delineate the extent of structural brain abnormalities in TSC have been developed. Diffusion tensor imaging unveils the microstructural abnormalities of the brain lesions and of the morphologically normal appearing white matter in TSC. It can potentially identify the epileptogenic zone. Positron emission tomography scanning with 2-deoxy-2 [18F]fluoro-D-glucose can assess the full extent of functional brain abnormalities in TSC. The use of alpha [11C] methyl-L-tryptophan positron emission tomography scanning has proven to be a useful tool in the identification of epileptogenic tubers and has improved the outcome of surgery for epilepsy in TSC. SUMMARY: Major advances of neuroimaging in TSC have shown evidence of widespread structural and functional brain abnormalities. In TSC patients with intractable epilepsy, new neuroimaging modalities can now provide an accurate assessment of the epileptogenic zone, thereby permitting improved identification of patients who can have good seizure outcome following surgery for epilepsy. PMID- 17351484 TI - Prospects for gene therapy in inherited neurodegenerative diseases. AB - PURPOSE OF REVIEW: The use of gene therapy to correct or replace deficient genes has been a long-standing aspiration. RECENT FINDINGS: Recent findings from basic and applied research suggest that at last it may be possible to translate experimental procedures into effective patient therapies for genetic diseases. Therapies for neurodegenerative diseases potentially include, as their targets, both monogenic conditions (e.g. lysosomal storage disorders) and more genetically complex diseases (such as Alzheimer's and Parkinson's disorders). SUMMARY: The use of gene therapy to target the central nervous system presents specific technical and biological challenges. These may be overcome by using novel gene vector delivery strategies. Current research should illuminate the temporal window required to achieve a successful therapy. As greater knowledge is accumulated about gene therapy, correlations will be made between the level of gene expression from the therapeutic vector, the extent of correction after treatment, and the stage of disease progression when therapy is initiated. PMID- 17351485 TI - The treatment of chronic epilepsy: a review of recent studies of clinical efficacy and side effects. PMID- 17351487 TI - Epilepsy. AB - PURPOSE OF REVIEW: To provide a critical review of studies published between December 2005 and November 2006, and detect the advances of basic and clinical research in epilepsy. RECENT FINDINGS: The complexity of the mechanisms underlying epileptogenesis and drug resistance was repeatedly highlighted. Seizure diagnosis and classification are still difficult, despite the use of valid and reliable instruments. Even well defined epilepsy syndromes may exhibit complex genetic patterns and atypical electroencephalogram features. Low prevalence rates of active epilepsy have been reported from several countries, suggesting underreporting for sociocultural reasons. Several pregnancy and neonatal factors can be found to increase the risk of epilepsy when accurate data are available from well defined populations. Early remission of seizures does not always predict terminal remission after prolonged follow-up. Cognitive regression may be associated with the presence of interictal electroencephalographic epileptiform abnormalities. A Cochrane review showed lamotrigine to be less frequently withdrawn than carbamazepine. However, these findings are contrasted by clinical practice, which showed no individual drug to be more likely to confer seizure freedom than any other. SUMMARY: Recent research highlights the complexity of the mechanisms of epileptogenesis and drug response, and the difficulties with the classification of epilepsy into separate phenotypic categories. PMID- 17351486 TI - Emerging epilepsy models: insights from mice, flies, worms and fish. AB - PURPOSE OF REVIEW: Animal models provide a means to investigate fundamental mechanisms of abnormal electrical discharge (i.e., seizures). Understanding the pathogenesis of epilepsy and therapy development have greatly benefited from these models. Here we review recent mouse mutants featuring spontaneous seizures and simpler organisms. RECENT FINDINGS: New genetically engineered mice provide additional insights to cellular mechanisms underlying seizure generation (BK calcium-activated potassium channels and interneuron-expressed sodium channels), genetic interactions that exacerbate seizure phenotype (Scn2a, Kcnq2 and background) and neurodevelopmental influences (Dlx transcription factors). Mutants for neuronal nicotinic acetylcholine receptors, Glut-1 deficiency and aquaporin channels highlight additional seizure phenotypes in mice. Additional models in Caenorhabditis elegans (Lis-1) and Danio rerio (pentylenetetrazole) highlight a reductionist approach. Taking further advantage of 'simple' organisms, antiepileptic drugs and genetic modifiers of seizure activity are being uncovered in Drosophila. SUMMARY: Studies of epilepsy in mutant mice provide a framework for understanding critical features of the brain that regulate excitability. These, and as yet undiscovered, mouse mutants will continue to serve as the foundation for basic epilepsy research. Interestingly, an even greater potential for analyzing epileptic phenotypes may lie in the more widespread use of genetically tractable organisms such as worms, flies and zebrafish. PMID- 17351488 TI - Teratogenesis of sodium valproate. AB - PURPOSE OF REVIEW: Sodium valproate has been a first-line antiepileptic drug for 40 years. A recent multicentre study conducted in the UK (Standard and New Antiepileptic Drugs) has confirmed what most practising neurologists had long suspected--that sodium valproate is the most effective drug in the treatment of idiopathic generalized epilepsy and juvenile myoclonic epilepsy. RECENT FINDINGS: Knowledge of the drug's unsurpassed efficacy has intensified the dilemma faced by neurologists treating people with epilepsy, and in particular young women. Recent data from pregnancy registers has not only confirmed that sodium valproate is teratogenic but also that it may be associated with neurodevelopmental delay and autistic spectrum disorders in the children of women exposed to the drug during pregnancy. Thus physicians have to balance the undoubted benefits of seizure freedom for their female patients with the potential long-term consequences for the infants of these patients. SUMMARY: There is undoubtedly a phamacogenetic component to sodium valproate's teratogenic and neurodevelopmental effects. Future research may enable us to identify those women whose offspring may be affected. Research now underway will help quantify the precise risk of neurodevelopmental delay in the offspring of women exposed to the drug, although it will be some years before results become available. PMID- 17351489 TI - Vaccination, seizures and 'vaccine damage'. AB - PURPOSE OF REVIEW: Concerns about the safety of vaccination have plagued the community, with reduction in vaccine uptake resulting in increased risk of epidemics. Vaccination has been implicated in the cause of febrile seizures, 'vaccine encephalopathy' and autistic spectrum disorders. Evaluation of alleged associations is complicated by evolution in the vaccination field. This review focuses on the risk of seizures following vaccination and the alleged associations of vaccination with vaccine encephalopathy and also with autism spectrum disorders. RECENT FINDINGS: Over the last decade the introduction of new vaccines such as the acellular pertussis vaccine has produced a reduction in seizures following vaccination, the outcome of which was benign even with older vaccines. New evidence emerged in 2006 showing that cases of alleged 'vaccine encephalopathy' are due to mutations within a sodium channel gene. The weight of epidemiological evidence does not support a relationship between vaccination and childhood epileptic encephalopathies or autism spectrum disorders. SUMMARY: Vaccines are safer than ever before, but the challenge remains to convey this message to society in such a way that produces change in attitudes to vaccination and subsequent increase in vaccine coverage. PMID- 17351490 TI - The anaesthetic and intensive care of status epilepticus. AB - PURPOSE OF REVIEW: Status epilepticus refractory to first and second-line anticonvulsants represents an outstanding challenge to the medical team. This review covers new insights into the anaesthetic and intensive care of status epilepticus. RECENT FINDINGS: In the anaesthetic treatment of status epilepticus, barbiturates, midazolam, or propofol are the drugs of choice, but the lack of controlled prospective data as yet does not allow the recommendation of a preference for one of the substances, unequivocally. Recent observational studies reported on inhalational anaesthetics and supplementary nonanaesthetics such as levetiracetam or topiramate that may be administered if status epilepticus is not controlled by intravenous anaesthetics. Nonpharmacological approaches including resective surgery, brain stimulation, and hypothermia may be applied in selected patients, only. Psychogenic nonepileptic status epilepticus commonly mimics refractory generalized convulsive status epilepticus, and clinical features discerning the two conditions are presented. The underlying cause is the major contributor for a difficult-to-treat 'malignant' course of status epilepticus and together with age determines mortality and functional outcome. SUMMARY: The common substances administered for the anaesthetic treatment of status epilepticus require assessment in a prospective randomized controlled trial. Alternative pharmacological or nonpharmacological approaches need further studies as well before they can be recommended as part of the therapeutic regime. PMID- 17351491 TI - The use of SPECT and PET in routine clinical practice in epilepsy. AB - PURPOSE OF REVIEW: The aim of this article is to give a subjective review of the usefulness of single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging in clinical practice in epilepsy for 2007. RECENT FINDINGS: Both ictal perfusion SPECT and interictal fluorodeoxyglucose PET can provide new information in the presurgical evaluation of intractable partial epilepsy. These functional imaging modalities reflect dynamic seizure-related changes in cerebral cellular functions. Although asymmetry of fluorodeoxyglucose PET metabolism has been useful to localize the epileptic temporal lobe, which tends to be more hypometabolic than the contralateral one, both frontal lobes are more hypometabolic than the epileptic temporal lobe, and may represent a region of 'surround inhibition'. Due to its low temporal resolution, ictal perfusion SPECT hyperperfusion patterns often contain both the ictal onset zone and propagation pathways. These patterns often have a multilobulated 'hourglass' appearance. The largest and most intense hyperperfusion cluster often represents ictal propagation, and does not always need to be resected in order to render a patient seizure free. SUMMARY: Optimized interictal FDG-PET and ictal perfusion SPECT as part of a multimodality imaging platform will be important tools to better understand the neurobiology of epilepsy and to better define the epileptogenic, ictal onset, functional deficit and surround inhibition zones in refractory partial epilepsy. PMID- 17351492 TI - Temporal lobe surgery in patients with normal MRI. AB - PURPOSE OF REVIEW: The surgical approach to nonlesional temporal lobe epilepsy presents a significant challenge due to uncertainties regarding the extent of resection necessary to result in a seizure-free state. To outline an optimum surgical strategy, an understanding of the clinical and diagnostic presentation of mesial and lateral temporal epilepsy is required in order to properly characterize the location of the ictal onset zone. This review focuses on several methods used to identify this ictal onset zone, with emphasis on the impact each modality has on surgical outcome. RECENT FINDINGS: Factors predicting an excellent surgical outcome include the presence of a discrete zone of low voltage fast activity and prolonged propagation time on the electroencephalogram, and the absence of metabolic dysfunction in the contralateral temporal lobe. Identifying epileptogenic regions in the temporal lobe using magnetic source imaging is a recent technique that has also yielded promising surgical outcomes. Recent prospective studies have shown that a temporal neocortical resection is very effective in providing a seizure free outcome given strict localization of the ictal onset zone to the lateral temporal region, highlighting the need for accurate characterization of mesial versus lateral nonlesional epilepsy. SUMMARY: With accurate identification of the ictal onset zone with intracranial electroencephalography, a tailored temporal resection can yield excellent surgical results. PMID- 17351493 TI - Prognosis of chronic and newly diagnosed epilepsy: revisiting temporal aspects. AB - PURPOSE OF REVIEW: The purpose is to review recent papers on the prognosis of epilepsy, with an emphasis on the importance of considering the temporal aspects of epilepsy. RECENT FINDINGS: The review considers five specific points: What is the chance of spontaneous remission without treatment (i.e. what is the natural history of untreated epilepsy)? What is the prognosis of epilepsy in newly diagnosed patients and how effective is therapy in previously drug-naive patients? Does delaying treatment make long-term prognosis worse? Is the prognosis of chronic established epilepsy inevitably bad? Refractory epilepsy, pharmaco-resistance and the influence of time. SUMMARY: This paper reviews the recent evidence that has provided data about temporal aspects of prognosis in epilepsy and confirms the importance of taking a synoptical view of prognosis, incorporating temporal aspects, in making clinical prognostic predictions. PMID- 17351495 TI - Bibliography. Current world literature. Developmental disorders. PMID- 17351494 TI - Mechanisms of status epilepticus: an evidence-based review. AB - (1) Status epilepticus is a significant health problem that is under-recognized, yet is associated with major morbidity and mortality. (2) Mechanisms accounting for status epilepticus emergence from a single seizure, and for prolonged status epilepticus duration, remain unclear. (3) No randomized controlled trials, systematic reviews, or meta-analyses were found in any of the databases searched regarding the pathophysiologic mechanisms of status epilepticus in humans. (4) Ongoing and future research is likely to more clearly define the pathogenetic mechanisms of status epilepticus. This, in turn, is likely to encourage better treatment 'targeting' for particular aspects of the condition. PMID- 17351496 TI - A model and reference data for retrospective dose assessment of organ doses (red bone marrow, lymphatic system) in diagnostic radiography and nuclear medicine, 1946-1995. AB - Retrospective dosimetry for radiologic and nuclear medicine examinations has been a challenge both for individual patients and in epidemiologic studies. Methodological problems include the large range of patient exposures from radiologic examinations, which spans over three orders of magnitude, the considerable dose reduction over time for most types of examinations due to technical advancements, and the increasing concern for radiation protection and quality issues in radiologic practice. A three-step model for retrospective dosimetry for patient exposure is presented that allows determination of organ doses to the red bone marrow and the lymphatic tissue, respectively, for typical examinations over the time period 1946-1995. The model starts from a set of doses assuming ideal technical equipment and radiologic practice. Step II considers the advancement of technical equipment over the different decades since the introduction of medical radiology in the early 1940's. Step III refers to quality in radiologic routine and allows for adjustment for less-than-ideal standards of radiologic practice. Model parameters are derived from contemporary literature and a multitude of historical sources. Tables with reference data are provided that allow a straightforward application of the model in the context of analytic epidemiologic studies. Wherever possible, reference doses are based on dose area product to allow for easy adjustment to different settings and inclusion of prospective data. The model and the results can be readily extended to different countries with different technical advancement and standard of radiologic practice. PMID- 17351497 TI - Assessment of intakes and doses to workers followed for 15 years after accidental inhalation of 60CO. AB - Intakes and doses are assessed for seven workers who accidentally inhaled particles containing Co in the same incident. Comprehensive whole body data to 15 y, and some early urine and fecal data, are available for each individual. The biokinetic and dosimetric models currently recommended by ICRP have been used to assess these cases. It was not possible to obtain good fits to the data using the ICRP models with their default parameter values. However, good fits to all the measurement data were obtained by varying parameter values following a procedure similar to that recommended in recently developed guidelines for assessment of internal doses from monitoring data. It was found that retention in the lungs was much longer than predicted by the ICRP Human Respiratory Tract Model, and so for each case it was necessary to reduce the particle transport clearance of material from the deep lungs. This reduction in lung clearance rates, and the use of specific AMAD values, were the dominating factors in changing assessed doses from those calculated using ICRP default values. PMID- 17351498 TI - Catch-up of delayed tooth eruption associated with uranium intoxication. AB - The population at large is at risk of oral exposure to uranium. Previous studies performed at our laboratory showed delayed tooth eruption 7 d post-administration of a single oral dose of uranyl nitrate in newborn rats. Rat kidney exhibiting severe damage 2 d post-acute uranyl nitrate exposure showed signs of recovery after 7 d; however, tooth eruption and development were significantly lower as compared with their age-matched controls. The aim of the present work was to establish whether tooth eruption and development, delayed by uranium exposure, can catch up to normal values at longer experimental times. In addition, since it is well documented that uranium intoxication by other routes of entry causes alterations in bone growth, we also aimed to evaluate the effect of oral exposure to uranium on mandibular growth. An experimental group of 16 1-d-old Wistar rats received a single 90 mg kg-1 body weight oral dose of uranyl nitrate. Another group of 16 age-matched rats received an equal volume of saline solution and served as the control. Eight animals in each group were killed 7 d post treatment, and the remaining animals were killed 27 d after the onset of the experiment. Morphometric measurements of mandibular growth were performed on radiographs. Tooth eruption and development were evaluated histomorphometrically on histologic sections obtained at the level of the mesial root of the first molar. Our results showed that the tooth eruption, dental development, and mandibular growth retardation observed 7 d post-acute uranyl nitrate exposure caught up completely after 27 d. PMID- 17351499 TI - Cytogenetic observations in human peripheral blood leukocytes following in vitro exposure to THz radiation: a pilot study. AB - Emerging technologies are considering the possible use of Terahertz radiation in different fields ranging from telecommunications to biology and biomedicine. The study of the potential effects of Terahertz radiation on biological systems is therefore an important issue in order to safely develop a variety of applications. This paper describes a pilot study devoted to determine if Terahertz radiation could induce genotoxic effects in human peripheral blood leukocytes. For this purpose, human whole blood samples from healthy donors were exposed for 20 min to Terahertz radiation. Since, to our knowledge, this is the first study devoted to the evaluation of possible genotoxic effects of such radiation, different electromagnetic conditions were considered. In particular, the frequencies of 120 and 130 GHz were chosen: the first one was tested at a specific absorption rate (SAR) of 0.4 mW g-1, while the second one was tested at SAR levels of 0.24, 1.4, and 2 mW g-1. Chromosomal damage was evaluated by means of the cytokinesis block micronucleus technique, which also gives information on cell cycle kinetics. Moreover, human whole blood samples exposed to 130 GHz at SAR levels of 1.4 and 2 mW g-1 were also tested for primary DNA damage by applying the alkaline comet assay immediately after exposure. The results obtained indicate that THz exposure, in the explored electromagnetic conditions, is not able to induce either genotoxicity or alteration of cell cycle kinetics in human blood cells from healthy subjects. PMID- 17351500 TI - Spatial variation of waterborne radon and temporal variation of radon in water at nine Maine schools. AB - Nine elementary schools in Maine were examined to track the release of 222Rn and to determine the transfer coefficient from water into air. Water-use simulations were performed by running sinks and sprayers for 1 h in a kitchen. The 222Rn in air was measured over 24 h throughout the school. The subsequent release of 222Rn into the kitchen air was measured to be greater than the EPA action level of 0.15 Bq L-1 (4 pCi L-1), but negligible concentrations of 222Rn were found in adjacent classrooms. In two schools, more than 10 222Rn-in-air detectors were placed throughout the kitchen and showed a three-fold spatial concentration variation. During the hour-long simulations, the 222Rn in water concentration was measured periodically, and many of the schools showed an increase in the 222Rn concentration in water before remaining constant. These measured variations suggest that multiple detectors are needed to accurately measure waterborne 222Rn in air, and multiple delayed measurements of 222Rn dissolved in water are needed to obtain a representative groundwater sample. PMID- 17351501 TI - Atomic bomb induced 152Eu: reconciliation of discrepancy between measurements and calculation. AB - In order to resolve the discrepancy between the measured and calculated 152Eu activity induced by the atomic bomb at Hiroshima, extremely low background gamma ray spectrometry was performed for 17 granite samples collected from 134 m to more than 3 km from the hypocenter. Measurements agreed well with theoretical calculations based on DS02 up to 1.4 km from hypocenter. PMID- 17351502 TI - Lung cancer risk associated to exposure to radon and smoking in a case-control study of French uranium miners. AB - A case-control study nested in the cohort of French uranium miners took smoking information into account in investigating the effect of radon exposure on lung cancer risk. This study included 100 miners who died of lung cancer and 500 controls matched for birth period and attained age. Data about radon exposure came from the cohort study, and smoking information was retrospectively determined from a questionnaire and occupational medical records. Smoking status (never vs. ever) was reconstructed for 62 cases and 320 controls. Statistical analyses used conditional logistic regression. The effect of radon exposure on lung cancer risk was assessed with a linear excess relative risk model, and smoking was considered as a multiplicative factor. Mean cumulative radon exposures were 114.75 and 70.84 Working Level Months (WLM) among exposed cases and controls, respectively. The crude excess risk of lung cancer per 100 WLM was 0.98 (95% CI: 0.18-3.08%). When adjusted for smoking, the excess risk was 0.85 per 100 WLM (95% CI: 0.12-2.79%), which is still statistically significant. The relative risk related to smoking was equal to 3.04 (95% CI: 1.20-7.70). This analysis shows a relative risk of lung cancer related to smoking similar to that estimated from previous miners' cohorts. After adjustment for smoking, the effect of radon exposure on lung cancer risk persists, and its estimated risk coefficient is close to that found in the French cohort without smoking information. PMID- 17351503 TI - Analysis of tenth-value-layers for common shielding materials for a robotically mounted stereotactic radiosurgery machine. AB - Tenth-value-layers (TVLs) for a 6 MV stereotactic radiosurgery (SRS) x-ray beam have been computed using Monte Carlo methods for radiation transport simulation. The first and equilibrium TVLs were determined in the three most common building materials used in radiation therapy vault construction: ordinary concrete, lead, and steel (iron). In contrast to broad-beam 6 MV TVL data found in the literature, the SRS TVLs can change rapidly with the size of the radiation field incident on the barrier. This research has investigated characteristics of TVLs as a function of field size (diameter) at the barrier for all materials, with special attention given to the TVL properties in iron. The x-ray spectrum used to perform these simulations was generated for the CyberKnife accelerator with the BEAMnrc Monte Carlo code. Using this spectrum as input to the MCNP5 Monte Carlo code, predicted tissue-maximum-ratio (TMR) values for a 6-cm-diameter field (at 80 cm from the target) were benchmarked against measured TMR data. The MCNP5 code was used to simulate all barrier transmissions, keeping the standard error of each data point below 1% of the mean. Results compare very well with previous measured concrete TVLs and also with published broad-beam 6 MV TVL data for all three barrier materials. PMID- 17351504 TI - Measurement of the leakage radiation from linear accelerators in the backward direction for 4, 6, 10, 15, and 18 MV x-ray energies. AB - The x-ray leakage from the housing of a therapy x-ray source is regulated to be <0.1% of the useful beam exposure at 1 m from the source. It is to be expected that the machine leakage in the backward direction would be less because the gantry and stand contain significant amounts of additional metal to attenuate the x rays. A reduction in head leakage in this direction will have a direct effect on the thickness of the shielding wall behind the linear accelerator. However, no reports have been published to date on measurements in this area. The x-ray leakage in the backward direction has been measured from linacs having energies of 4, 6, 10, 15, and 18 MV using a 100 cm ionization chamber and Al2O3 dosimeters. The leakage was measured at nine different positions over the rear wall using a 3 x 3 matrix with a 1-m separation between adjacent horizontal and vertical points with either the leftmost or rightmost column aligned with the target and isocenter. In general, the leakage is less than the canonical value, but the exact value depends on energy, gantry angle, and measurement position. There is significantly greater attenuation directly behind the gantry stand for all energies. Leakage at 10 MV for some positions exceeded 0.1%. Additionally, neutron leakage measurements were made for 10, 15, and 18 MV x-ray beams using track-etch detectors. The average neutron leakage was less than 0.1% except for 18 MV, where neutron leakage was more than 0.1% of the useful beam at some positions. PMID- 17351505 TI - A gamma camera re-evaluation of potassium iodide blocking efficiency in mice. AB - The protection of the thyroid against radioiodine uptake has been an important safety concern for decades. After several studies examined potassium iodide blockade efficacy in the 1960's and 1970's, a standard dosage was prescribed by both the World Health Organization and the U.S. Food and Drug Administration. In this paper, we tested the effectiveness of a scaled version of that standard dosage in comparison to higher doses in mice. A novel gamma camera was employed with a high spatial resolution for precisely quantifying activity within the thyroid and a field of view large enough to image the entire mouse body. Thyroid and whole-body 125I biodistribution was analyzed immediately after exposure and 1 and 7 days later. It was found that 1 h after exposure five times the scaled human dose blocked thyroid uptake about 40% more effectively than the 1X scaled dose. Even after 1 d and 7 d, five times the recommended scaled human dose blocked approximately 10% more effectively than the 1X dose. These data suggest the need for continued evaluation of the effectiveness of KI as a blocking agent and the application of novel, non-invasive technologies to this important human health issue. PMID- 17351509 TI - Return to work-from research to practice. PMID- 17351510 TI - Impact of topiramate migraine prophylaxis on workplace productivity: results from two US randomized, double-blind, placebo-controlled, multicenter trials. AB - OBJECTIVE: We conducted this study to determine whether topiramate at 100 mg/d for the treatment of migraine headache is associated with improved productivity in the workplace. METHODS: Results were derived from two randomized, double blind, placebo-controlled trials among migraineurs. The number of hours of absenteeism (A), presenteeism (P), and total lost productivity (TLP) (A + P) were calculated. Results were not adjusted for multiplicity. RESULTS: A total of 325 (162 in the topiramate group and 163 in the placebo group) of 449 subjects were included. Per person mean monthly A rate was only significantly less for individuals within the topiramate group (1.0 hours per person) versus those in the placebo group (1.5 hours per person) for month 3 (P < 0.05). Per person mean P and TLP rates were significantly lower for individuals in the topiramate group versus those in the placebo group for months 1 through 5 (P < 0.05). CONCLUSIONS: Findings suggest that topiramate, compared with placebo, is associated with decreased workplace presenteeism and TLP. PMID- 17351511 TI - Influence of personal exposure to particulate air pollution on cardiovascular physiology and biomarkers of inflammation and oxidative stress in subjects with diabetes. AB - OBJECTIVE: We investigated whether personal exposure to particulate matter a 5 mm space deficiency). The following parameters were measured and used to compare the two groups: individual and collective mesiodistal tooth diameters, dental arch length, as well as buccal and lingual dental arch widths in the canine and molar regions. To compare the two groups the Student's t-test with 95% confidence interval was used. RESULTS: Statistically significant differences in both tooth diameters and transverse arch dimensions were found between the two groups. The crowded group was found to have a significantly smaller maxillary arch width and larger tooth size when compared with the uncrowded group. CONCLUSION: The results of this study suggest under equal conditions (a Class I skeletal relationship) tooth size has a greater role in developing dental crowding. PMID- 17351682 TI - Prevalence, clinical picture, and risk factors of dry socket in a Jordanian dental teaching center. AB - AIMS: The aims of this study were to determine the prevalence, clinical picture, and risk factors of dry socket at the Dental Teaching Center of Jordan University of Science and Technology (DTC/JUST). METHODS AND MATERIALS: Two specially designed questionnaires were completed over a four-month period. One questionnaire was completed for every patient who had one or more permanent teeth extracted in the Oral Surgery Clinic. The other questionnaire was completed for every patient who returned for a post-operative visit and was diagnosed with dry socket during the study period. RESULTS: There were 838 dental extractions carried out in 469 patients. The overall prevalence of dry socket was 4.8%. There was no statistically significant association between the development of dry socket and age, sex, medical history, medications taken by the patient, indications for the extraction, extraction site, operator experience, or the amount of local anesthesia and administration technique used. The prevalence of dry socket following non-surgical extractions was 3.2%, while the prevalence following surgical extractions was 20.1% (P< 0.002). The prevalence of dry socket following surgical and non-surgical extractions was significantly higher in smokers (9.1%) than in non-smokers (3%) (P = 0.001), and a direct linear trend was observed between the amount of smoking and the prevalence of dry socket (P = 0.034). The prevalence of dry socket was significantly higher in the single extraction cases (7.3%) than in the multiple extraction cases (3.4%) (P = 0.018). The clinical picture and management of dry socket at DTC/JUST were similar to previous reports in the literature. The prevalence of dry socket, its clinical picture, and management at DTC/JUST are similar to those reported in the literature. CONCLUSION: Smoking and surgical trauma are associated with an increased incidence of dry socket. Moreover, patients who had single extractions were more likely to develop dry socket than those who had multiple extractions in the same visit. PMID- 17351683 TI - Attitudes of Romanian dental students towards tobacco and alcohol. AB - AIM: The aim of this study was to assess smoking and alcohol use in male and female Romanian dental students and to compare this with different levels of education. METHODS AND MATERIALS: A total of 315 questionnaires were distributed to male and female dental students (first to sixth year students). RESULTS: Among the 315 respondents, 37.33% were smokers and 71.04% o f students used alcohol on a regular basis. Overall, there was a 30-day smoking prevalence of 32.47%. Among those who smoked daily, 24% were sixth year students and only 10% were first year. The average number of cigarettes smoked was thirteen cigarettes per day with males smoking more than females (p<0.0001). The average number of years as a smoker was five years, with fifth and sixth year students smoking longer than others (p<0.001). The average age when students started to smoke was 17.15 years. Statistically significant differences were observed between genders related to alcohol drinking (p<0.0001). Significant linear relationships were shown between smoking and alcohol consumption (r;2=0.47, p<0.0001). CONCLUSION: There was a clear difference in smoking and alcohol consumption between groups of Romanian dental students. PMID- 17351684 TI - Hematoma following periodontal surgery with a torus reduction: a case report. AB - BACKGROUND: There are no published case reports that hematomas occur on the floor of the mouth as a result of periodontal surgery. REPORT: These three case reports document post surgical hematoma formation on the floor of the mouth that pose problems with the diagnosis, prognosis, and patient management. All cases involved periodontal surgery where extensive reduction of tori and bony exostoses were required. Two cases resulted in hematomas in the floor of the mouth. However, a change in the post surgical management for a third case demonstrated possible prevention of hematoma formation. SUMMARY: Hematomas in the floor of the mouth can be a resolving post surgical phenomenon or a serious vascular insult to this region of the oral cavity. This report clarifies the diagnosis, prognosis, and the best management protocol through the presentation of three cases. PMID- 17351685 TI - Diagnosis and treatment of atypical odontalgia: a review of the literature and two case reports. AB - AIM: This report presents two cases diagnosed with atypical odontalgia (AO) and successfully treated with amitriptyline as well as providing a review of the current literature on the subject. RESULTS: The literature indicates the most important issue is an accurate differential diagnosis to distinguish between AO, pulpal pain, myofascial pain, and trigeminal neuralgia. CONCLUSION: Once the correct diagnosis is made the prognosis of AO is usually fair and the administration of tricyclic antidepressants often resolves symptoms. An effort should be made to avoid any unnecessary dental treatment that would only aggravate the problem. PMID- 17351686 TI - Epidermoid cyst of the buccal mucosa: a case report. AB - AIM: The purpose of this article is to describe a rare case of an epidermoid cyst in the buccal cheek region and a review of the literature. BACKGROUND: Dermoid and epidermoid cysts are developmental pathologies occurring in the head and neck region with an incidence ranging from 1.6% to 6.9%, and both cysts reported in less than 0.01% of all oral cavity cysts. REPORT: A rare case of an epidermoid cyst originating from the buccal mucosa in a 38-year-old woman with a complaint of swelling and facial asymmetry in the left cheek just distal to the commissure for six months is presented in this report. PMID- 17351687 TI - Severe hemorrhage during an incisional biopsy: a report of a case. AB - BACKGROUND: Surgical procedures under local anesthesia are routinely employed by the dentist and are susceptible to significant complications which demand immediate care from the dental professional. REPORT: This report presents a case of severe arterial hemorrhage during a simple removal of a lesion during an incisional biopsy. SUMMARY: In the event of severe arterial hemorrhage in a conventional dental office, manual compression for containing the hemorrhage and use of an adequate light source to correctly visualize the origin of the bleeding is recommended. If visible, the dental surgeon must attempt to perform vascular ligature or an occlusive suture. If the hemorrhage cannot be controlled after these measures, the patient must be transported to a hospital while continuing local compression during transit. PMID- 17351688 TI - Transmigration of mandibular canines: a report of six cases and a review of the literature. AB - BACKGROUND: The transmigration of a mandibular canine is a rare phenomenon, the etiology of which is not clear. The literature on this rare condition is reviewed, and six cases of transmigrated mandibular canines are presented. REPORT: Panoramic radiographic examination of six patients revealed each patient had one impacted transmigrated mandibular canine. Of the six impacted teeth, the left mandibular canine was involved in four instances and the right in two. In one case the transmigrated canine was associated with a dentigerous cyst. SUMMARY: Transmigration of the mandibular canine is a rare event, and early radiographic examination of the patient is important for treatment. In addition, future studies may lead to a better understanding of this rare anomaly and improvement of the classification criteria. PMID- 17351689 TI - Facilitating recovery: evidence for organized stroke care. AB - Despite dramatic advances in the management of thrombolysis and acute stroke, organized rehabilitation remains the cornerstone of recovery from stroke. The importance of organized stroke care in facilitating recovery has been recognized for the last 10 years, but it is still unclear how organized rehabilitation contributes to improved outcomes. This paper presents a synthesis of evidence of the benefits of organized care, especially with respect to stroke severity and different types of organized stroke care. It presents an overview of possible processes within organized rehabilitation that may contribute to good outcomes. The role of integrated care pathways within rehabilitation settings is discussed, highlighting the limitations of current evidence and uncertainty about their benefits. Finally, some key challenges have been identified for stroke units in improving rehabilitation outcomes over the next decade and for healthcare planners in investing adequately in organized stroke services. PMID- 17351690 TI - Early supported discharge after stroke. AB - Patients after stroke conventionally receive much of their rehabilitation in hospital. Services have been developed that offer patients an early discharge from hospital with more rehabilitation at home (early supported discharge). This paper sets out a systematic review of all randomized trials of early supported discharge services that included 12 trials (1659 patients). There was a reduced odds of death or dependency equivalent to 5 fewer adverse outcomes (95% confidence interval 1-10) for every 100 patients receiving an early supported discharge service (p = 0.04). Patients receiving early supported discharge services showed an 8 day reduction (p < 0.0001) in the length of hospital stay. The greatest benefits were seen in the trials evaluating a co-ordinated multidisciplinary early supported discharge team and with patients with mild moderate disability. The experience of a trial from Stockholm is described in order to explore the potential mechanism of action of early supported discharge services. In conclusion, an illustrative case report is set out, indicating a typical patient pathway in an early supported discharge service. PMID- 17351691 TI - Stroke, complex regional pain syndrome and phantom limb pain: can commonalities direct future management? AB - Despite being different conditions, complex regional pain syndrome type 1, phantom limb pain and stroke share some potentially important similarities. This report examines experimental and clinical findings from each patient population. It identifies common aspects of symptomatic presentation, sensory phenomena and patterns of cortical reorganization. Based on these common findings, we argue that established principles of stroke rehabilitation are also applicable to rehabilitation of complex regional pain syndrome type 1 and phantom limb pain. In addition, we contend that promising treatment approaches for complex regional pain syndrome type 1 and phantom limb pain may be helpful in stroke rehabilitation. Examples of emerging supportive evidence for these hypotheses are provided and discussed. PMID- 17351692 TI - Evaluation of botulinum toxin therapy of spastic equinus in paediatric patients with cerebral palsy. AB - OBJECTIVE: To develop a clinical and instrumental protocol to assess the postural and dynamic effects following treatment with botulinum neurotoxin A in children with cerebral palsy affected by spastic equinus. DESIGN: Open study, in which every patient served as his or her own control. PATIENTS: Ten sequential children with cerebral palsy and spastic dynamic equinus foot. METHODS: Botulinum neurotoxin A was injected in the gastrocnemius, soleus and tibialis posterior muscles. The main measures were: pedobarometry, dynamic surface electromyography, video gait analysis scale, and the modified Ashworth Scale. RESULTS: After treatment with botulinum neurotoxin A, pedobarometric evaluation revealed a significant change in all parameters, including a decrease in the modified Ashworth Scale and an increase in the range of motion. All children showed significant improvement in initial foot contact, as documented by the video gait analysis scale. The calf muscle electromyography pattern showed a decrease in co contraction during gait in all children. These modifications were statistically significant for all parameters considered (p < 0.05). CONCLUSION: This pilot study suggests that dynamic electromyography and pedobarometry are simple to use and provide useful data; this protocol could be preferable in young and uncooperative children in order to monitor rehabilitation treatments. PMID- 17351693 TI - Analysing the favourable effects of physical exercise: relationships between physical fitness, fatigue and functioning in Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy. AB - OBJECTIVE: To elucidate the effects of physical exercise in severely fatigued patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy, and to clarify the mutual relationships between 5 domains studied in these patients: physical fitness, fatigue, objectively measured actual mobility, perceived physical functioning, and perceived mental functioning. DESIGN: Case series. SUBJECTS/PATIENTS: Twenty patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy. METHODS: The patients undertook a 12-week physical exercise program. Relationships between domains were studied in the change scores, and additionally in the baseline data of patients. The percentage of significant relationships between each pair of domains was determined. RESULTS: In the change scores, a small percentage of significant relationships was found between the physical fitness domain and the other 4 domains (2/30, 7%). A higher percentage of significant relationships was found between the domains perceived mental functioning and actual mobility (44%), perceived mental functioning and perceived physical functioning (44%), and between fatigue and perceived physical functioning (33%). Generally, similar patterns were found in the baseline data. CONCLUSION: Changes in fatigue, actual mobility and perceived functioning seem not to be influenced by changes in physical fitness. This study stresses the presence and importance of additional effects of a physical training program, not directly related to increasing fitness. PMID- 17351694 TI - Stretching exercises vs manual therapy in treatment of chronic neck pain: a randomized, controlled cross-over trial. AB - OBJECTIVE: To compare the effects of manual therapy and stretching exercise on neck pain and disability. DESIGN: An examiner-blinded randomized cross-over trial. PATIENTS: A total of 125 women with non-specific neck pain. METHODS: PATIENTS were randomized into 2 groups. Group 1 received manual therapy twice weekly and Group 2 performed stretching exercises 5 times a week. After 4 weeks the treatments were changed. The follow-up times were after 4 and 12 weeks. Neck pain (visual analogue scale) and disability indices were measured. RESULTS: Mean value (standard deviation) for neck pain was 50 mm (22) and 49 mm (19) at baseline in Group 1 and Group 2, respectively, and decreased during the first 4 weeks by 26 mm (95% Confidence Interval 20-33) and 19 mm (12-27), respectively. There was no significant difference between groups. Neck and shoulder pain and disability index decreased significantly more in Group 1 after manual therapy (p=0.01) as well as neck stiffness (p=0.01). CONCLUSION: Both stretching exercise and manual therapy considerably decreased neck pain and disability in women with non-specific neck pain. The difference in effectiveness between the 2 treatments was minor. Low-cost stretching exercises can be recommended in the first instance as an appropriate therapy intervention to relieve pain, at least in the short term. PMID- 17351695 TI - Test-retest reliability of psychophysical lift capacity in patients with non specific chronic low back pain and healthy subjects. AB - OBJECTIVE: Psychophysical lift capacity tests are lifting tests in which the performance, expressed in Newtons, is divided by the perceived exertion, expressed on a Borg scale. The aim of this study was to analyse test-retest reliability of psychophysical lift capacity tests. SUBJECTS: Patients with non specific chronic low back pain (n=20) and healthy subjects (n=20). METHODS: Psychophysical lift capacity tests were assessed during a back school intake at the Centre for Rehabilitation of the University Medical Centre Groningen. Patients on the waiting list and healthy subjects were assessed twice, with a 2 week interval between assessments. Intra-class correlation (ICC) was calculated as a measure of reliability. An ICC > or = 0.75 was considered as an acceptable reliability. Limits of agreement as a measure for natural variation were calculated. RESULTS: The psychophysical static and dynamic lift capacity tests showed good reliability (ICC > or = 0.75). The limits of agreement are substantial, indicating a considerable natural variation between test-sessions for all psychophysical tests. CONCLUSION: The psychophysical static lift capacity and dynamic lifting capacity are reliable instruments for patients with non specific chronic low back pain and healthy subjects. However, a substantial amount of natural variation should be taken into account between 2 test sessions when interpreting the test results clinically. PMID- 17351696 TI - Measuring mobility in people with lower limb amputation: Rasch analysis of the mobility section of the prosthesis evaluation questionnaire. AB - OBJECTIVE: To assess the psychometric properties of the Mobility Section of the Prosthesis Evaluation Questionnaire (PEQ-MS). DESIGN: A postal survey, including self-report assessment of prosthetic capability and performance with the PEQ-MS and the Locomotor Capabilities Index, and of other variables associated with prosthetic wear and use. The PEQ-MS data underwent Rasch analysis for rating scale diagnostics and a reliability and validity study. PATIENTS: A total of 123 subjects (mean age 54 years) who had undergone lower limb amputation in the previous 5 years and who had completed rehabilitation and a prosthetic training programme. RESULTS: According to Rasch analysis and expert review, some response categories of the PEQ-MS (13 items, 11-level numeric rating scale) were collapsed and one item was deleted. The remaining 12 items fitted to the Rasch model and created a revised scale with a 5-level response format, the PEQ-MS12/5. The PEQ MS12/5 demonstrated good reliability (person-separation reliability = 0.95, item separation reliability = 0.98) and internal construct validity. Moreover, the correlation with the Locomotor Capabilities Index (rs = 0.78) and with prosthetic wear and use (rs range 0.41-0.59) supported the convergent validity of the PEQ MS12/5. CONCLUSION: The new PEQ-MS12/5 presents good psychometric characteristics for measuring mobility in people with lower limb amputations. These preliminary results provide an already applicable instrument and a solid basis for further validation studies. PMID- 17351697 TI - Mortality after spinal cord injury in Norway. AB - OBJECTIVES: To study mortality, cause of death and risk indicators for death in Norwegian patients with spinal cord injury. DESIGN: A cross-sectional study with retrospective data. SUBJECTS: All patients (n=387) with traumatic spinal cord injury admitted to Sunnaas Rehabilitation Hospital, Norway, during the period 1961-82. METHODS: Medical records were reviewed retrospectively. Causes of death were collected from Statistics Norway and death certificates. Standardized mortality ratios (SMRs) were calculated for the entire sample and for causes of death. To explore risk indicators for death, a Cox regression model was used. RESULTS: During the observation period, 1961-2002, 142 patients died. The main causes of death were pneumonia/influenza (16%), ischaemic heart diseases (13%) and urogenital diseases (13%). SMR was 1.8 for men and 4.9 for women. Cause specific SMRs were markedly elevated for urogenital diseases, suicide, pneumonia/influenza, urogenital cancer, and diseases of the digestive system. Risk indicators for death were: higher age at injury, tetraplegia, functionally complete spinal cord injury, pre-injury cardiovascular disease, alcohol or substance abuse and psychiatric diagnosis. CONCLUSION: The SMRs show that life expectancy is reduced in chronic spinal cord injury in Norway, more for women than for men. Cause-specific SMRs and risk indicators suggest that the high mortality rates after spinal cord injury to a certain degree are related to preventable aetiologies. To maximize longevity in chronic spinal cord injury, more attention must be paid to co-morbidity. PMID- 17351698 TI - Sexual activity and satisfaction in men with traumatic spinal cord lesion. AB - OBJECTIVE: To estimate sexual activity and sexual satisfaction in men with spinal cord lesion. DESIGN: Cross-sectional study. SUBJECTS: All adult citizens in Helsinki with traumatic spinal cord lesion were identified. The final study group comprised 92 male subjects, corresponding to a participation rate of 79%. METHODS: A structured questionnaire was sent to all subjects and they were invited for a clinical visit. Clinical examination was based on the manual of the American Spinal Injury Association (ASIA). Examinations were performed on all subjects by the same experienced physician and physiotherapist. RESULTS: In total, 86% of the subjects experienced sexual desire and 68% had been sexually active during the last 12 months. A total of 65% of subjects reported experiencing orgasm since the injury, but most subjects rated it as weaker than before the injury. There were no statistically significant differences between the ASIA Impairment Scale groups. Men with paraplegia reported a more satisfactory sex life (p = 0.05) than those with tetraplegia. CONCLUSION: This study confirms the earlier findings that the ability to reach orgasm is deficient in men with spinal cord lesion. The completeness of the lesion had no effect. The more severe locomotory disability might adversely affect the sex life of persons with tetraplegia compared with those with paraplegia. PMID- 17351699 TI - Impact on participation and autonomy questionnaire: internal scale validity of the Swedish version for use in people with spinal cord injury. AB - OBJECTIVE: To evaluate aspects of internal scale validity and reliability of the Swedish version of the Impact on Participation and Autonomy questionnaire (IPA-S) for use in people with spinal cord injury. SUBJECTS: A total of 161 persons with spinal cord injury. METHOD: IPA-S psychometric properties were evaluated using Rasch rating scale analysis. RESULTS: The results show that the IPA-S has 27 items for perceived participation and 6 items for perceived problems with participation, indicating 2 underlying unidimensional constructs for use in people with spinal cord injury, after removal of misfitting items. The established hierarchical order of the item calibration values in both scales appeared logical and the distances between the items, with a few exceptions in the problem scale, were appropriate. Both scales demonstrated good separation reliability. The range of item calibration values in both scales did not fully cover the range of measures of persons' perceived participation and problems thereof. CONCLUSION: The psychometric properties of IPA-S are promising and indicate that IPA-S has potential to be developed further. PMID- 17351700 TI - Cross-diagnostic validity of the SF-36 physical functioning scale in patients with stroke, multiple sclerosis and amyotrophic lateral sclerosis: a study using Rasch analysis. AB - OBJECTIVE: The aim of this study was to investigate unidimensionality and differential item functioning of the SF-36 physical functioning scale (PF10) in patients with various neurological disorders. PATIENTS: PATIENTS post-stroke (n = 198), with multiple sclerosis (n = 151) and amyotrophic lateral sclerosis (n = 193) participated. METHODS: Unidimensionality of the PF10 within the patient groups was investigated by performing a separate Rasch analysis for each group. Differential item functioning was investigated in a pooled Rasch analysis of the 3 groups. RESULTS: Within each group, all items fitted the Rasch model, except the "bathing/dressing" item in the amyotrophic lateral sclerosis group. The pooled analysis showed inadequate fit to the Rasch model for one item ("walking several hundred metres"). Of the other 9 fitting items, 5 showed differential item functioning for stroke vs multiple sclerosis and amyotrophic lateral sclerosis, while no differential item functioning was found between multiple sclerosis and amyotrophic lateral sclerosis. CONCLUSION: All items of the PF10, except one for the amyotrophic lateral sclerosis group, form a unidimensional scale, supporting the use of a sum score as a measure of physical functioning within these diagnostic groups. When comparing the data of patients after stroke, with that of patients with multiple sclerosis and/or amyotrophic lateral sclerosis patients, adjustments for differential item functioning are required. PMID- 17351701 TI - Gait in hemiplegia: evaluation of clinical features with the Wisconsin Gait Scale. AB - OBJECTIVE: To assess the ability of the Wisconsin Gait Scale to evaluate qualitative features of changes in hemiplegic gait in post-stroke patients. DESIGN: A prospective observational study. SUBJECTS: Ten healthy subjects and 56 hemiplegic outpatients, more than 12 months post-stroke, consecutively admitted in a rehabilitation centre. METHODS: Patients were videotaped while walking at a comfortable speed. Quantitative and clinical gait parameters were derived from videotaped walking tasks at admission and at the end of a period of rehabilitation training. Qualitative features were assessed using the Wisconsin Gait Scale. Functional status was rated through the modified Barthel Index. RESULTS: After training, the median Wisconsin Gait Scale score improved significantly (28 vs 26.5; p = 0.003). In particular, "weight shift to paretic side" and patterns during the swing phase of the affected leg were improved. Gait velocity (0.3 vs 0.4 m/sec; p = 0.001) and stride length (77 vs 85 cm; p = 0.0002) increased significantly, whereas number of steps (25 vs 23; p = 0.004), stride period (2.5 vs 2.3 sec; p = 0.04), and stance period (2.1 vs 2 sec; p = 0.03) of the unaffected side were reduced. The Barthel Index score increased (71 vs 78; p = 0.005). CONCLUSION: The Wisconsin Gait Scale is a useful tool to rate qualitative gait alterations of post-stroke hemiplegic subjects and to assess changes over time during rehabilitation training. It may be used when a targeted and standardized characterization of hemiplegic gait is needed for tailoring rehabilitation and monitoring results. PMID- 17351702 TI - Disability in a 4-year follow-up study of people with post-polio syndrome. AB - OBJECTIVE: To evaluate changes over time in a clinically based cohort of individuals with post-polio syndrome. DESIGN: A prospective longitudinal study. SUBJECTS: A total of 106 individuals with poliomyelitis sequelae were included in the study. They were self-referred or had been referred to the post-polio clinic. After 4 years subjects were called for a follow-up and underwent the same measurements as at the initial assessment. METHODS: The following measurements were conducted at both the initial assessment, and the follow-up: questionnaires including Nottingham Health Profile, muscle strength and walking speed. RESULTS: Minor changes in disability during a 4-year period were shown. A significant reduction in muscle strength was only seen for 60 degrees flexion in the left leg and for right and left dorsal flexion. No change could be seen in the total Nottingham Health Profile score. CONCLUSION: The minor changes in disability found in this study are an indication that we still do not know which subjects are at risk for deterioration. It is difficult to say whether the small changes over time shown in this study are associated with support from the polio clinic or are an expression of the natural history of the syndrome. However, it is hoped that support from the polio clinic may result in self-selected lifestyle changes, which may positively influence the development of symptoms and functional capacity. PMID- 17351703 TI - Gait recovery in a distal spinal muscular atrophy patient wearing a patellar tendon-bearing orthosis and orthopaedic shoes. AB - OBJECTIVE: To illustrate that a patient with distal spinal muscular atrophy can recover gait with a combination of orthoses and orthopaedic shoes. SUBJECT: A 28 year-old man with distal spinal muscular atrophy affecting only the distal muscles of the lower limbs. Clinical examination showed a bilateral pes cavus with a varus and a 90 degrees equinus of the ankle joint. METHODS: The patient was fitted with orthopaedic shoes and a patellar tendon-bearing orthosis. In order to assess the clinical effects of this fitting, a complete physical examination was performed and the patient's temporo-spatial gait parameters were assessed quantitatively using gait analysis tools (Gaitrite) both prior to treatment and after one month. RESULTS: Before the fitting, the patient was not able to walk alone or to maintain an upright position and he suffered from foot pain. One month after the fitting was applied, the patient was able to walk alone and to maintain an upright position for 1 hour. His pain disappeared. Quantified study of the patient's gait parameters shows that the temporo-spatial parameters are close to normal with fitting. CONCLUSION: Clinical and quantitative data both confirm the subjective improvements reported by the patient. PMID- 17351704 TI - A new procedure for communication with a patient with minimal motor function and fatigability. AB - As with eye movements in locked-in syndrome, severe motor dysfunction should be coped with by an agreed system of interpretation to express feelings and needs. However, it is possible that such patients might make errors in the agreed system of interpretation through fatigue, which would cause misunderstandings. We report here a new questioning and verifying strategy for an agreed system of interpretation. Our questioning strategy is characterized by repeating questions in different forms, specifically by affirmative and negative sentences (Double Checked agreed system of interpretation). When the patient wants to express "Yes", a single movement is required for an affirmative question and no movement is required for a negative one. When the patient wants to express "No", no movement is required for an affirmative question and one movement is required for a negative one. The Double-Checked agreed system of interpretation can help patients to cope with fatigability and can also help to prevent misunderstandings. If the same responses to both affirmative and negative questions are given, we can consider that those answers reflect fatigue. In addition, we have developed a strategy to evaluate the patient's understanding of the Double-Checked agreed system of interpretation by modifying the Western Aphasia Battery. This report describes how to apply the Double-Checked agreed system of interpretation, using the example of a 48-year-old brain-injured man with minimal motor function and severe fatigability. PMID- 17351705 TI - Potentiation of botulinum toxin type A with oral anti-spasticity medications in the management of focal spasticity. PMID- 17351706 TI - Coupling of capillary electroseparation techniques with mass spectrometric detection. PMID- 17351707 TI - Instrumental modification intended to save time, and volumes of sample and reagent solutions, in the atomic fluorescence spectrometric determination of mercury. AB - Use of small membrane pumps, instead of peristaltic pumps, to introduce sample and reagent solutions into the spectrometer has several advantages in atomic fluorescence spectrometric determination of mercury. This simple modification results in a substantial saving in the time required for the measurements and so 90% of reagent solution volumes and 95% of sample solution volumes are saved, with a consequent decrease in the volume of waste generated. The sampling frequency is almost tripled, with no deterioration in sensitivity, which is similar to that obtained by use of peristaltic pumps. The relative standard deviation for ten consecutive measurements of a 1 microg L-1 mercury solution was approximately 2%. PMID- 17351708 TI - Confirmation of a genetic locus for X-linked recessive high myopia outside MYP1. AB - High myopia is a severe ocular condition affecting approximately 100 million people throughout the world. It is a common cause of blindness, and several studies have suggested it is transmitted through Mendelian traits. High myopia is clinically and genetically heterogeneous, with eight loci assigned. Most loci have not been confirmed by additional studies, and genes responsible for high myopia have not been identified. We recently studied a Chinese family with X linked high myopia and mapped the high myopia locus to Xq25-q27.2. This linked region overlapped with that of MYP13 but was outside MYP1. PMID- 17351709 TI - The ACVR1 617G>A mutation is also recurrent in three Japanese patients with fibrodysplasia ossificans progressiva. AB - Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and presents progressive extra-skeletal ossification. The 617G>A (R206H) mutation in the activin receptor type IA (ACVR1) gene has been identified in all examined individuals with FOP of various ethnic groups, including Caucasian and Chinese descents. Here, we examined three Japanese patients with FOP for ACVR1 mutations. We identified the 617G>A mutation in all three patients. Our results suggest that the mutation in the ACVR1 gene is common and recurrent in the global population. PMID- 17351710 TI - Two novel nonsense mutations in GALNT3 gene are responsible for familial tumoral calcinosis. AB - Ectopic periarticular calcifications associated with elevated levels of serum phosphate represent the principal clinical features of hyperphosphatemic familial tumoral calcinosis (HFTC), a rare autosomal recessive metabolic disorder. The disease can be caused by recessive mutations in at least two different genes: GalNAc transferase 3 (GALNT3), encoding a glycosyltransferase that initiates mucin-type O-glycosylation, and fibroblast growth factor 23 (FGF23), which encodes a regulator of phosphate circulating levels. In the current study, we performed mutation analyses of the GALNT3 gene in a subject with HFTC and in his relatives. Sequence analyses revealed that the proband was a compound heterozygote for two novel nonsense mutations in exon 4 (Y322X) and in exon 7 (Q481X). Cosegregation of the mutations with the disease within the family was confirmed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. This is the first report describing the simultaneous presence of two different stop codons in the coding sequence of the GALNT3 gene. PMID- 17351711 TI - Advances in polyamine research in 2007. AB - Polyamines are small aliphatic amines found in all living organisms except some Archaea. In plants, putrescine, spermidine, and spermine are major components which are not only involved in fundamental cellular processes, for example cell proliferation, differentiation, and programmed cell death, but also in adaptive responses to environmental stress. In this article we review plant polyamine research focusing on recent studies. PMID- 17351712 TI - Induction and inhibition of cyclobutane pyrimidine dimer photolyase in etiolated cucumber (Cucumis sativus) cotyledons after ultraviolet irradiation depends on wavelength. AB - Under polychromatic ultraviolet (UV) irradiation (maximum energy at 327 nm) the activity of DNA photolyase specific to cyclobutane pyrimidine dimers (CPDs), CPD photolyase, increased by an amount which depended on UV irradiance, and the level of CPD photolyase gene (CsPHR) transcripts temporarily increased before the activity reached a constant level. UV light (>320 nm) was more effective than visible light at increasing CPD photolyase activity. In contrast, monochromatic UV irradiation at wavelengths <300 nm increased the level of CsPHR transcripts similarly to irradiation at wavelengths >320 nm, but reduced CPD photolyase activity compared with the dark control. Exposure of a CPD photolyase solution to UV-C (254 nm) reduced enzyme activity and induced accumulation of H(2)O(2). Addition of H(2)O(2) to the enzyme solution also inactivated CPD photolyase activity. These results suggest the possibility that reactive oxygen species participate in the inactivation of CPD photolyase in cotyledons exposed to UV irradiation of <300 nm. PMID- 17351713 TI - An electric frequency-to-place map for a cochlear implant patient with hearing in the nonimplanted ear. AB - The aim of this study was to relate the pitch of high-rate electrical stimulation delivered to individual cochlear implant electrodes to electrode insertion depth and insertion angle. The patient (CH1) was able to provide pitch matches between electric and acoustic stimulation because he had auditory thresholds in his nonimplanted ear ranging between 30 and 60 dB HL over the range, 250 Hz to 8 kHz. Electrode depth and insertion angle were measured from high-resolution computed tomography (CT) scans of the patient's temporal bones. The scans were used to create a 3D image volume reconstruction of the cochlea, which allowed visualization of electrode position within the scala. The method of limits was used to establish pitch matches between acoustic pure tones and electric stimulation (a 1,652-pps, unmodulated, pulse train). The pitch matching data demonstrated that, for insertion angles of greater than 450 degrees or greater than approximately 20 mm insertion depth, pitch saturated at approximately 420 Hz. From 20 to 15 mm insertion depth pitch estimates were about one-half octave lower than the Greenwood function. From 13 to 3 mm insertion depth the pitch estimates were approximately one octave lower than the Greenwood function. The pitch match for an electrode only 3.4 mm into the cochlea was 3,447 Hz. These data are consistent with other reports, e.g., Boex et al. (2006), of a frequency to-place map for the electrically stimulated cochlea in which perceived pitches for stimulation on individual electrodes are significantly lower than those predicted by the Greenwood function for stimulation at the level of the hair cell. PMID- 17351714 TI - Efficient expression and primary purification of 6-his tagged human Fas ligand in Dictyostelium discoideum. AB - Human Fas ligand (hFasL) is a member of the tumor necrosis factor (TNF) family with many medical interests. To produce this protein efficiently, an improved vector which could express the recombinant hFasL protein with a 6-his tag at its C-terminal was constructed. The new vector was transformed into Dictyostelium discoideum AX3 which then produced 157 microg hFasL l(-1). Using one-step Ni affinity chromatography, it was purified with a recovery of 92% and purity of 91%. PMID- 17351715 TI - RifP; a membrane protein involved in rifamycin export in Amycolatopsis mediterranei. AB - The rifamycin gene cluster in Amycolatopsis mediterranei includes the gene rifP, whose role in antibiotic production has not yet been established. In this work, the rifP gene was silenced and the results indicated that it codes for a protein to export rifamycin, avoiding its accumulation inside the cell. An antisense cassette was constructed by inserting the rifP gene in an antisense orientation downstream from the modified ermE* promoter, and upstream of the Tasd terminator (aspartate semialdehyde dehydrogenase of A. lactamdurans). Partial silencing of the rifP gene by the use of the antisense cassette, cloned in the plasmid pUAMAE5, resulted in a 70% decrease in the extracellular rifamycin B. A protein of 53 kDa was absent in the membrane fraction of the silenced strain. This is the same size of the expected product from the rifP gene. The 2D structure analysis indicated it belongs to a Drug:H+ antiporter family which includes a wide number of membrane transport proteins. PMID- 17351716 TI - Solvent-free synthesis of glyceryl ferulate using a commercial microbial lipase. AB - A process was optimized for the enzymatic synthesis of glyceryl ferulate with a yield of up to 96% using a vacuum-rotary evaporation strategy under following conditions: 15 mmol glycerol, 1.5 mmol ethyl ferulate, 170 mg Candida antarctica lipase, at 60 degrees C for 10 h and under a vacuum of 10 mm Hg. The immobilized lipase can be used 10 times. PMID- 17351717 TI - Introduction to bioreactors of shake-flask inocula leads to development of oxidative stress in Aspergillus niger. AB - Inoculation of bioreactors with shake-flask cultures present the organism with an immediate shift from an environment with little O2 to one in which O2 is typically at 100% saturation. The inoculation of such shake-flasks cultures into bioreactors sparged with 1 vvm air or 1 vvm air/O2 mix i.e. 50% O2 enrichment is an oxidatively stressful event, as judged by immediate increases in the intracellular concentrations of superoxide anion radical (O2*-) (from 4,600 to 11,600 RLU mg DCW(-1) and 5,500 to 23,000 RLU mg DCW(-1) respectively) and changes in the activities of the major antioxidant enzymes superoxide dismutase and catalase in all cultures. There are further effects on metabolic indices, particularly decreased nutrient consumption in oxygenated cultures (from 0.16 to 0.12 g starch g DCW h(-1)) and decreased protein production, indicating that inoculation of the bioreactor exerts a global burden on the cellular metabolic networks. PMID- 17351718 TI - Cervical stump prolapse complicating laparoscopic supracervical hysterectomy in a nulliparous woman. AB - A resurgence of supracervical hysterectomies is being seen, as providers are becoming more comfortable with minimally invasive surgery. Proponents of this technique advocate that leaving the cervix prevents the disruption of proper anatomical relationships, which allows better apical support of the vagina. We report a case of cervical stump prolapse 6 months after a laparoscopic supracervical hysterectomy (LSH) in a 36-year-old, nulliparous, obese woman who demonstrated excellent uterine support before her surgery. PMID- 17351719 TI - Adjustable continence therapy for the treatment of urinary incontinence after radical cystectomy and orthotopic neobladder in women. AB - The management of urinary incontinence after radical cystectomy and orthotopic neobladder reconstruction is a very challenging situation. We report on a patient that developed a neobladder-urethro-vaginal fistula successfully treated but resulting in severe urinary incontinence that was cured after the periurethral insertion of adjustable silicone balloons. PMID- 17351720 TI - CBF changes in drug naive juvenile myoclonic epilepsy patients. AB - PURPOSE: The role of thalamus and brainstem in generalized epilepsy has been suggested in previous studies. The aim of the present study was to assess regional cerebral blood flow (rCBF) abnormality in juvenile myoclonic epilepsy (JME) patients. METHODS: (99m)Tc-ethylcysteinate dimer brain single photon emission computed tomography (SPECT) was performed in 19 drug naive JME patients and 25 normal controls with the similar age and gender distribution. Differences of rCBF between a JME group and a normal control group were examined by the statistical parametric mapping of brain SPECT images using independent t test. The regression analyses in SPM were also performed between rCBF and the age of seizure onset or the disease duration in JME group. RESULTS: Compared to normal controls, the JME group showed a significant rCBF reduction in bilateral thalami, red nucleus, midbrain, pons, left hippocampus, and in the cerebelli (FDR corrected p < 0.01) whereas rCBF increase in the left superior frontal gyrus (uncorrected p < 0.001 but FDR corrected p > 0.05). Disease duration was negatively correlated with rCBF in bilateral frontal cortices, caudate nuclei, brainstem and cerebellar tonsils. CONCLUSIONS: Our results suggest that abnormal neural networks in the thalamus, hippocampus, brainstem and cerebellum are associated with JME. PMID- 17351721 TI - Functional involvement of cerebral cortex in adult sleepwalking. AB - The pathophysiology of adult sleepwalking is still poorly understood. However, it is widely accepted that sleepwalking is a disorder of arousal. Arousal circuits widely project to the cortex, including motor cortex. We hypothesized that functional abnormality of these circuits could lead to changes in cortical excitability in sleepwalkers, even during wakefulness. We used transcranial magnetic stimulation (TMS) to examine the excitability of the human motor cortex during wakefulness in a group of adult sleepwalkers. When compared with the healthy control group, short interval intracortical inhibition (SICI), cortical silent period (CSP) duration, and short latency afferent inhibition (SAI) were reduced in adult sleepwalkers during wakefulness. Mean CSP duration was shorter in patients than in controls (80.9 +/- 41 ms vs. 139.4 +/- 37 ms; p = 0.0040). Mean SICI was significantly reduced in patients than in controls (73.5 +/- 38.4% vs. 36.7 +/- 13.1%; p = 0.0061). Mean SAI was also significantly reduced in patients than in controls (65.8 +/- 14.2% vs. 42.8 +/- 16.9%; p = 0.0053). This neurophysiological study suggests that there are alterations in sleepwalkers consistent with an impaired efficiency of inhibitory circuits during wakefulness. This inhibitory impairment could represent the neurophysiological correlate of brain "abnormalities" of sleepwalkers like "immaturity" of some neural circuits, synapses, or receptors. PMID- 17351722 TI - Association of daytime sleepiness with nigrostriatal dopaminergic degeneration in early Parkinson's disease. AB - INTRODUCTION: Many patients with Parkinson's disease (PD) report daytime sleepiness. Its etiology, however, is still not fully understood. The aim of this study was to examine if the amount of nigrostriatal dopaminergic degeneration is associated with subjective daytime sleepiness in patients with PD. PATIENTS AND METHODS: We investigated 21 patients with PD clinically and by means of [(123)I] FP-CIT-SPECT (DaTSCAN(R)). Each patient filled in the Epworth sleepiness scale (ESS), the Parkinson's Disease Sleep Scale (PDSS), and the self-rating depression scale according to Zung (SDS) to assess sleepiness, sleep quality, and depressive symptoms. RESULTS: The mean specific dopamine transporter binding in the 21 PD patients (60.8 +/- 10.4 years, nine females, median Hoehn and Yahr stage 2.0) was decreased. Nine patients were in Hoehn and Yahr stage 1 (58.7 +/- 6.6 years, four females; ESS score 7.4 +/- 4.5; PDSS score 105.1 +/- 30.9), the other 12 patients were in Hoehn and Yahr stage 2 (62.4 +/- 12.6 years, five females; ESS score 6.7 +/- 4.7, PDSS score 97.1 +/- 25.6). Age, gender, ESS, and PDSS scores were not significantly different in both groups. However, ESS scores showed an inverse correlation with mean DAT binding in the striatum (r = -0.627, p = 0.03), the caudate nucleus (r = -0.708, p = 0.01), and the putamen (r = -0.599, p = 0.04) in patients with Hoehn and Yahr stage 2. There was no correlation of the ESS score with age, disease duration, UPDRS motor score, PDSS score, or depression score. CONCLUSION: Subjective daytime sleepiness seems to be associated with dopaminergic nigrostriatal degeneration in early PD. PMID- 17351723 TI - Increased serotonin transporter availability in the brainstem of migraineurs. AB - For decades, serotonin has been speculated to play a major role in migraine pathophysiology. The central serotonergic system is located in the raphe nuclei and the adjacent reticular formation in the brainstem. Recently, radioligands targeting the brain serotonin transport protein (SERT) have been developed. We used the highly specific SERT-radioligand (123)I-ADAM [2-((2-((dimethylamino) methyl)phenyl)thio)-5-iodophenylamine] to test the hypothesis of the mesopontine serotonergic system being involved in the pathophysiology of migraine. Nineteen migraine patients and 10 healthy, age- and sex-matched controls were enrolled. The neuroimaging study was performed interictally during the pain-free interval. Single Photon Emission Computed Tomography (SPECT)-images were coregistered with MRI-scans. Region of interest (ROI)-analysis revealed a highly significant increase of (123)I-ADAM uptake in the mesopontine brainstem of migraineurs (p < 0.001). In contrast, (123)IADAM uptake in the thalamus did not differ significantly between migraineurs and controls. Our study demonstrates for the first time a significant increase of brainstem SERT-availability in migraineurs, suggesting a dysregulation of the brainstem serotonergic system. It remains to be elucidated whether the altered SERT-availability is causally related to migraine pathophysiology or whether it reflects secondary pathophysiological mechanisms. PMID- 17351724 TI - Glatiramer acetate induced acute exacerbation of autoimmune hepatitis in a patient with multiple sclerosis. PMID- 17351725 TI - Does sleep protect against ischemic stroke? Less frequent ischemic strokes but more severe ones. AB - BACKGROUND AND OBJECTIVE: Stroke occurrence follows a circadian curve, with a higher frequency in the morning. This curve changes if the hours of sleep also change. Our aim was to evaluate the characteristics, risk factors, and prognosis associated with sleep stroke. METHODS: Patients with ischemic stroke (n = 813), consecutively assessed in our hospital for 2 years, were recorded with the time of clinical onset, pathological antecedents, severity (NIHSS), clinical classification, etiologic TOAST classification, and functional outcome at 3 months (modified Rankin scale). When clinical disturbance appeared during night sleep time it was considered as sleep stroke (SS). The rest were considered wakefulness stroke (WS). Differences SS-WS were analyzed with chi(2), t-student, Mann-Whitney U, and logistic regression tests. RESULTS: From 813 patients included, 127 were SS (15.6%). The SS frequency was less than expected for the corresponding interval of hours. After the univariate analysis and posterior logistic regression, obesity was a factor associated with SS. Adjustment for age and gender revealed that atrial fibrillation (AF) was less frequent in the SS group. There were no differences for other risk factors or in the etiologic distribution. SS had a greater initial clinical severity and a worse functional outcome at 3 months. This functional outcome was dependent on the initial clinical severity. CONCLUSIONS: Whilst sleep could be associated with a lesser stroke occurrence, it could also be associated with a higher severity. Obesity appears as a factor related to SS whilst AF appears related to WS. PMID- 17351726 TI - Fatigue: an important feature of late-onset Pompe disease. AB - OBJECTIVE: To investigate the prevalence and severity of fatigue in adult patients with Pompe disease. METHODS: The Fatigue Severity Scale (FSS) was assessed in an international population of 225 adults with Pompe disease, a metabolic disorder presenting as a slowly progressive proximal myopathy. The FSS scores were compared to those of healthy controls and the relationship between the level of fatigue and other patient characteristics was investigated. RESULTS: The mean age of the participants was 47 (SD 13) years and the mean disease duration 11 (SD 8) years. 43% used a wheelchair and 46% had respiratory support, 29% needed both. 67% of the participants had a FSS score > or =5, indicating severe fatigue. The mean FSS score was 5.2 (SD 1.5), which was significantly higher than that of healthy controls (p < 0.001). Fatigue was not related to age, sex or disease duration. Patients who used a wheelchair or respiratory support were on average more fatigued than those who did not (p = 0.01). However, of the patients who did not use these aids, 59% also had a FSS score > or =5. FSS scores were highest among patients who reported a high frequency of sleep disorders, but patients who never experienced sleep difficulties were also fatigued (mean FSS score = 4.8). CONCLUSION: Fatigue is highly prevalent among both mildly and severely affected adult patients with Pompe disease. The FSS appears a useful tool in assessing fatigue in Pompe disease. PMID- 17351727 TI - Encephalitis lethargica following Bartonella henselae infection. PMID- 17351729 TI - Steroid responsive encephalopathy with positive thyroid antibodies. A syndrome, not a diagnosis? PMID- 17351730 TI - Plant immunity: cellular aspects of signaling. PMID- 17351731 TI - Clathrin is involved in organization of mitotic spindle and phragmoplast as well as in endocytosis in tobacco cell cultures. AB - We previously identified a 175 kDa polypeptide in Lilium longiflorum germinating pollen using a monoclonal antibody raised against myosin II heavy chain from Physarum polycephalum. In the present study, the equivalent polypeptide was also found in cultured tobacco BY-2 cells. Analysis of the amino acid sequences revealed that the 175 kDa polypeptide is clathrin heavy chain and not myosin heavy chain. After staining of BY-2 cells, punctate clathrin signals were distributed throughout the cytoplasm at interphase. During mitosis and cytokinesis, clathrin began to accumulate in the spindle and the phragmoplast and then was intensely concentrated in the cell plate. Expression of the C-terminal region of clathrin heavy chain, in which light chain binding and trimerization domains reside, induced the suppression of endocytosis and the formation of an aberrant spindle, phragmoplast, and cell plate, the likely cause of the observed multinucleate cells. These data strongly suggest that clathrin is intimately involved in the formation of the spindle and phragmoplast, as well as in endocytosis. PMID- 17351732 TI - Temperature-sensitive formation of chloroplast protrusions and stromules in mesophyll cells of Arabidopsis thaliana. AB - In leaf mesophyll cells of transgenic Arabidopsis thaliana plants expressing GFP in the chloroplast, stromules (stroma-filled tubules) with a length of up to 20 mum and a diameter of about 400-600 nm are observed in cells with spaces between the chloroplasts. They appear extremely dynamic, occasionally branched or polymorphic. In order to investigate the effect of temperature on chloroplasts, we have constructed a special temperature-controlled chamber for usage with a light microscope (LM-TCC). This LM-TCC enables presetting of the temperature for investigation directly at the microscope stage with an accuracy of +/-0.1 degrees C in a temperature range of 0 degrees C to +60 degrees C. With the LM-TCC a temperature-dependent appearance of chloroplast protrusions has been found. These structures have a considerably smaller length-to-diameter ratio than typical stromules and reach a length of 3-5 mum. At 5-15 degrees C (low temperatures), almost no chloroplast protrusions are observed, but they appear with increasing temperatures. At 35-45 degrees C (high temperatures), numerous chloroplast protrusions with a beaklike appearance extend from a single chloroplast. Interaction of stromules with other organelles has also been investigated by transmission electron microscopy. At 20 degrees C, transverse sections of stromules are frequently observed with a diameter of about 450 nm. A close membrane-to-membrane contact of stromules with the nucleus and mitochondria has been visualised. Golgi stacks and microbodies are found in the spatial vicinity of stromules. At 5 degrees C, virtually no chloroplast protrusions or stromules are observed. At 35 degrees C, chloroplast protrusions are present as broader thylakoid-free stroma-filled areas, resulting in an irregular chloroplast appearance. PMID- 17351733 TI - Below-ambient levels of UV induce chloroplast structural change and alter starch metabolism. AB - Electromagnetic radiation (EMR) in the 400-700 nm bandwidth of photosynthetically active radiation (PAR) has been established as an important source of energy for photosynthesis and environmental signals regulating many aspects of green-plant life. Above-ambient levels of UV-B radiation (290-320 nm) under high-PAR conditions have been shown to elicit responses in chloroplasts of Brassica napus similar to those of chloroplasts at low-PAR exposure (W. Fagerberg and J. Bornman, Physiol. Plant. 101: 833-844, 1997). The question arises as to whether UV at normal levels can also evoke similar responses. Here we provide evidence that even below-ambient levels of UV-B (1/28 ambient; Durham, N.H., U.S.A., 1200 hours, March) were capable of inducing an increase in thylakoid surface area relative to the chloroplast volume typical of a low-PAR response (shade response) in sunflowers. This response occurred even though leaves were concurrently exposed to PAR levels that normally induce a "sun" or high-PAR response in the absence of UV-B. Subambient levels of UV-B were also associated with a decrease in chloroplast and starch volume. Exposure to levels of UV-A 1/10 of ambient appeared to enhance the high-PAR response of the chloroplast, characterized by an increase in the amounts of stored starch, an increase in chloroplast volume density ratio values, and a decrease in thylakoid surface area density ratios relative to the high-light controls. These effects were opposite to those seen in UV-B-exposed tissue. In a general sense, subambient levels of UV-B evoked a response similar to that elicited by low-PAR irradiance, while subambient UV-A elicited responses similar to those typical of high-PAR irradiance. The fact that below-ambient levels of UV altered a normal chloroplast structural response to PAR provides evidence that UV may be an important environmental signal for plants. PMID- 17351734 TI - Characteristics of motive force derived from trajectory analysis of Amoeba proteus. AB - We used a monochromatic charge-coupled-device camera to observe the migration behavior of Amoeba proteus every 5 s over a time course of 10000 s in order to investigate the characteristics of its centroid movement (cell velocity) over the long term. Fourier transformation of the time series of the cell velocity revealed that its power spectrum exhibits a Lorentz type profile with a relaxation time of a few hundred seconds. Moreover, some sharp peaks were found in the power spectrum, where the ratios of any two frequencies corresponding to the peaks were expressed as simple rational numbers. Analysis of the trajectory using a Langevin equation showed that the power spectrum reflects characteristics of the cell's motive force. These results suggest that some phenomena relating to the cell's motility, such as protoplasmic streaming and the sol-gel transformation of actin filaments, which seem to be independent phenomena and have different relaxation times, interact with each other and cooperatively participate in the generation process of the motive force. PMID- 17351735 TI - Dynamics and localization of H2O2 production in elicited plant cells. AB - H(2)O(2) produced in plant cells plays a dual role. In addition to its antimicrobial effect, it also acts as a secondary messenger initiating and modulating responses of plants exposed to unfavorable external signals. A suspension culture of Rubia tinctorum cells challenged with elicitors was used as a model system to investigate H(2)O(2) formation. Cellular H(2)O(2) was measured by a modified titanium(IV) method, while that in the medium was detected with scopoletin fluorescence. Localization of H(2)O(2) production at the ultrastructural level was carried out by the CeCl(3) reaction. A fungal elicitor induced H(2)O(2) production with transient maxima, the first of which appeared 4 min after treatment. Three subsequent maxima appeared in the cells up to 48 h after treatment. Exposure of cells to exogenous jasmonic acid and salicylic acid also changed the H(2)O(2) concentration maxima over 48 h; however, their timing was slightly shifted. Fungal-elicitor, jasmonic acid, and salicylic acid treatments had different effects on the H(2)O(2) concentration in the medium. Ultrastructural investigations revealed that electron-dense precipitates were present at the plasmalemma and in some nearby vesicular cytoplasmic structures 30 min after treatment. Later samples showed cytochemical-precipitate accumulation in the cell walls. These deposits appeared to be local and independent of the direction of the external signal. We could not detect the presence of H(2)O(2) in peroxisomes, mitochondria, plastids, or the central vacuolar space. Electron energy loss spectroscopy investigations distinguished between the cerium containing precipitates and other electrondense particles, thereby proving that H(2)O(2) generation occurs locally. PMID- 17351736 TI - The movement protein BC1 promotes redirection of the nuclear shuttle protein BV1 of Abutilon mosaic geminivirus to the plasma membrane in fission yeast. AB - In order to monitor their interaction and cellular localisation, the movement protein (MP; syn. BC1) and the nuclear shuttle protein (NSP; syn. BV1) of the geminivirus Abutilon mosaic virus (AbMV) were ectopically expressed in Schizosaccharomyces pombe cells, either alone or together under the control of an inducible promoter. For highest resolution, electron microscopy using freeze fracture immunolabelling served to detect these proteins in situ. As expected from previous in planta and yeast experiments, NSP accumulated within the nuclei, whereas MP was targetted to the protoplasmic face of plasma membranes when expressed alone. Upon coexpression, NSP was localised at the plasma membranes, where it was strongly attached. These results support a model in which NSP transports viral DNA to the cell periphery to facilitate cell-to-cell movement of viral DNA within plants. In contrast to AbMV MP, no plant-specific protein seems to be necessary for the translocation of NSP to the plasma membrane. PMID- 17351737 TI - Even if you build it, we may not come: correlates of non-attendance at a sexual risk reduction workshop for STD clinic patients. AB - Sexual risk reduction interventions have been shown to reduce sexual risk behavior; however, attendance at these interventions is sometimes disappointingly low. To improve recruitment efforts, we investigated whether patient characteristics were associated with non-attendance at a single-session, sexual risk reduction intervention. Patients from an STD clinic (N = 990; 48% female; 64% African American) who were eligible and who agreed to participate in a randomized, clinical trial were invited to a 4-h, sexual risk reduction workshop. Fifty-six percent of those who were invited attended the workshop. Those who did not attend were more likely to be younger, male, Caucasian, and employed. Attendance did not differ as a function of sexual behavior or infection status. These findings identify the population sub-groups who are likely to require special effort to attract to a workshop. We encourage more effective marketing and recruitment approaches for sexual risk reduction programs. PMID- 17351738 TI - Does patient-provider racial/ethnic concordance influence ratings of trust in people with HIV infection? AB - Despite widely available and effective treatments, there are racial/ethnic disparities in HIV-related mortality rates. The reason for inadequate HIV/AIDS management among minority populations is not fully understood, however recent research indicates that patients rate the quality of their health care higher if they are racially/ethnically concordant with their providers. As trust plays prominently on health care ratings, we examined whether racial/ethnicity concordance was associated with two dimensions of trust, trust in the provider and mistrust in the health care system, in 380 HIV infected people New York City. In this sample, concordance was associated with lower mistrust in the health care system, but not with trust in provider. We conclude that in this patient population and within the health care system available to them, racial/ethnic concordance might be more important for helping patients to understand and navigate the health care system rather than in interpersonal relationships with a single provider. PMID- 17351739 TI - SAHA induces apoptosis in hepatoma cells and synergistically interacts with the proteasome inhibitor Bortezomib. AB - Histone deacetylase (HDAC) inhibitors represent a promising group of anticancer agents. This paper shows that the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) stimulated at 5-10 microM apoptosis in human hepatoma HepG2 and Huh6 cells, but was ineffective in primary human hepatocytes (PHH). In HepG2 cells SAHA induced the extrinsic apoptotic pathway, increasing the expression of both FasL and FasL receptor and causing the activation of caspase-8. Moreover, SAHA enhanced the level of Bim proteins, stimulated alternative splicing of the Bcl-X transcript with the expression of the proapoptotic Bcl-Xs isoform, induced degradation of Bid into the apoptotic factor t-Bid and dephosphorylation and inactivation of the anti-apoptotic factor Akt. Consequently, SAHA caused loss of mitochondrial transmembrane potential, release of cytochrome c from mitochondria, activation of caspase-3 and degradation of PARP. Interestingly, a combination of suboptimal doses of SAHA (1 microM) and bortezomib (5-10 nM), a potent inhibitor of 26S proteasome, synergistically induced apoptosis in both HepG2 and Huh6 cells, but was ineffective in PHH. Combined treatment increased with synergistic effects the expression levels of c-Jun, phospho-c-Jun and FasL and the production of Bcl-Xs. These effects were accompanied by activation of Bid, caspase-8 and 3. In conclusion, SAHA stimulated apoptosis in hepatoma cells and exerted a synergistic apoptotic effect when combined with bortezomib. In contrast, these treatments were quite ineffective in inducing apoptosis in PHH. Thus, our results suggest the potential application of the SAHA/bortezomib combination in clinical trials for liver cancer. PMID- 17351740 TI - The hunter-gatherer theory of sex differences in spatial abilities: data from 40 countries. AB - This study used some of the data from the BBC Internet study to assess the universality of sex related spatial competencies, as these are described in the terms of Silverman and Eals' (1992) hunter-gatherer theory of human spatial sex differences. As predicted, men scored significantly higher than women on a test of three-dimensional mental rotations in all seven ethnic groups and 40 countries used. Close to prediction, women scored significantly higher than men on a test of object location memory in all seven ethnic groups and 35 of the 40 countries. The data were discussed in terms of their implications for research approaches in this area and a paradigm for future studies was proposed, based on the interaction of innate and environmental factors in the ontogenetic development of spatial sex differences. PMID- 17351741 TI - Gender and sexual orientation differences in cognition across adulthood: age is kinder to women than to men regardless of sexual orientation. AB - Despite some evidence of greater age-related deterioration of the brain in males than in females, gender differences in rates of cognitive aging have proved inconsistent. The present study employed web-based methodology to collect data from people aged 20-65 years (109,612 men; 88,509 women). As expected, men outperformed women on tests of mental rotation and line angle judgment, whereas women outperformed men on tests of category fluency and object location memory. Performance on all tests declined with age but significantly more so for men than for women. Heterosexuals of each gender generally outperformed bisexuals and homosexuals on tests where that gender was superior; however, there were no clear interactions between age and sexual orientation for either gender. At least for these particular tests from young adulthood to retirement, age is kinder to women than to men, but treats heterosexuals, bisexuals, and homosexuals just the same. PMID- 17351742 TI - Dasatinib may also inhibit c-Kit in triple negative breast cancer cell lines. PMID- 17351743 TI - Correlation of levels and patterns of genomic instability with histological grading of invasive breast tumors. AB - Pathological grade is a useful prognostic factor for stratifying breast cancer patients into favorable (well-differentiated tumors) and less favorable (poorly differentiated tumors) outcome groups. The current system of tumor grading, however, is subjective and a large proportion of tumors are characterized as intermediate-grade tumors, making determination of optimal treatments difficult. To determine whether molecular profiles can discriminate breast disease by grade, patterns and levels of allelic imbalance (AI) at 26 chromosomal regions frequently altered in breast disease were examined in 185 laser microdissected specimens representing well-differentiated (grade 1; n = 55), moderately differentiated (grade 2; n = 71), and poorly-differentiated (grade 3; n = 59) stage I-IV breast tumors. Overall levels of AI were significantly higher in grade 3 compared to grade 1 tumors (P < 0.05). Grades 1 and 3 showed distinct genetic profiles--grade 1 tumors were associated with large deletions of chromosome 16q22, while alterations at 9p21, 11q23, 13q14, 17p13.1 and 17q12 were characteristics of grade 3 carcinomas. In general, levels and patterns of AI in grade 2 carcinomas were intermediate between grade 1 and grade 3 tumors. Patterns of AI accurately categorized approximately 70% of samples into high- or low-grade disease groups, suggesting that the majority of breast tumors have genetic profiles consistent with high- or low-grade, and that molecular signatures of breast tumors can be useful for more accurate characterization of invasive breast cancer. PMID- 17351744 TI - ATM allelic variants associated to hereditary breast cancer in 94 Chilean women: susceptibility or ethnic influences? AB - Besides BRCA1 and BRCA2, two genes accounting for a small proportion of breast cancer cases, ATM has been widely proposed as a low-penetrance susceptibility gene. Several nucleotide changes have been proposed to be associated with breast cancer, still remaining a high controversy in this sense. We screened the ATM gene in 94 breast cancer patients selected from 78 high-risk families, not presenting a mutation in BRCA1 or BRCA2. We found three novel allelic variants: IVS64 + 51delT and p.L752L, not showing association with hereditary breast cancer, and p.L694L found in one family in two breast cancer patients. Two amino acid substitutions p.S707P and p.F858L, previously reported to be associated with breast cancer, were present in our study in cases and controls, lacking of association with breast cancer. A positive association of c.5557G>A (p.D1853N) was found (OR 2.52, P = 0.008), when analyzed alone and in combination with an intronic variant IVS24-9delT (OR 3.97; P = 0.0003). We postulate that our discrepancies with other reports related to the associated ATM alleles to hereditary breast cancer, as well as discrepancies in the literature between other groups, could be explained by the diversity in the ethnic origins of families gathered in a sole study, and the selection of the control group. In relation to this issue, and based on genetic markers, we found that the Chilean group of breast cancer families in this study has a stronger European genetic component than our control sample selected randomly from the Chilean population. PMID- 17351745 TI - VRP immunotherapy targeting neu: treatment efficacy and evidence for immunoediting in a stringent rat mammary tumor model. AB - The ability to overcome intrinsic tolerance to a strict "self" tumor-associated antigen (TAA) and successfully treat pre-existing tumor is the most stringent test for anti-tumor immunotherapeutic strategies. Although this capacity has been demonstrated in various models using complicated strategies that may not be readily translated into the clinical arena, straightforward antigen-specific immunotherapeutic strategies in the most stringent models of common epithelial cancers have largely failed to meet this standard. We employed an immunotherapeutic strategy using an alphavirus-based, virus-like replicon particle (VRP), which has in vivo tropism for dendritic cells, to elicit immune responses to the non-mutated TAA rat neu in an aggressive rat mammary tumor model. Using this VRP-based immunotherapeutic strategy targeting a single TAA, we generated effective anti-tumor immunity in the setting of pre-existing tumor resulting in the cure of 36% of rats over multiple experiments, P = 0.002. We also observed down-regulation of rat neu expression in tumors that showed initial responses followed by tumor escape with resumption of rapid tumor growth. These responses were accompanied by significant anti-tumor proliferative responses and CD8+ cellular tumor infiltrates, all of which were restricted to animals receiving the anti-neu immunotherapy. Together these data, obtained in a stringent "self" TAA model, indicate that the VRP-based antigen-specific immunotherapy elicits sufficiently potent immune responses to exert immunologic pressure, selection, and editing of the growing tumors, thus supporting the activity of this straightforward immunotherapy and suggesting that it is a promising platform upon which to build even more potent strategies. PMID- 17351746 TI - A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women. AB - BACKGROUND: Many women experience symptoms of cyclical mastalgia, such as breast pain, tenderness, and nodularity. Tamoxifen and other drugs have been used to alleviate cyclical mastalgia symptoms; however, their use is associated with potentially serious side effects. The current study compared the safety and efficacy of two doses of a topical gel containing 4-hydroxytamoxifen (Afimoxifene, formerly known as 4-OHT) with placebo gel for the treatment of moderate to severe cyclical mastalgia. METHODS: Premenopausal women aged at least 18 years experiencing moderate to severe symptoms were randomized to receive placebo, 2 mg, or 4 mg of Afimoxifene daily delivered as a transdermal hydroalcoholic gel for 4 menstrual cycles. The primary efficacy parameter was change in mean pain intensity as measured by the Visual Analog Scale (VAS) for the seven worst pain score days within a cycle from baseline to the fourth cycle. RESULTS: After 4 cycles of treatment, statistically significant improvements relative to placebo were measured in mean VAS score in the 4-mg Afimoxifene group (-12.71 mm [95% confidence interval, -0.96 to -24.47; P = 0.034]). Patient global assessment of pain, physician's assessment of pain, tenderness on palpation, and nodularity following 4 cycles of treatment were significantly more likely to show improvements in the 4-mg group, compared with placebo (P = 0.010 [pain]; P = 0.012 [tenderness]; P = 0.017 [nodularity]). Overall, Afimoxifene was well tolerated with few adverse events and no drug-related SAE occurred in any group. There were no changes in menstrual pattern or plasma hormone levels and no breakthrough vaginal bleeding in patients treated with Afimoxifene. CONCLUSION: After 4 months of treatment, daily topical breast application of Afimoxifene resulted in statistically significant improvements in signs and symptoms of cyclical mastalgia across patient- and physician-rated scales with excellent tolerability and safety. PMID- 17351747 TI - Parent-adolescent collaboration: an interpersonal model for understanding optimal interactions. AB - Current parent-adolescent behavioral interaction research highlights the importance of three elements of behavior in defining adaptive interactions: autonomy, control, and warmth vs. hostility. However, this research has largely addressed the developmental needs and psychosocial outcomes of adolescents, as opposed to parents, with a focus on how parent and adolescent behaviors influence adolescent adaptation. This paper utilizes both adolescent and mid-life developmental research, as well as parent-adolescent interaction research, to introduce a model for conceptualizing parent-adolescent interactions as a transactional process in which both parental and adolescent development are considered. Further, ideas are presented describing how adaptive parent adolescent interactions may change across adolescence. The concept of collaboration is proposed as a conceptual tool for assessing one form of adaptive parent-adolescent interactions. The structural analysis of social behavior (SASB) is presented as a model for studying the complex reciprocal processes that occur in parent-adolescent interpersonal processes. PMID- 17351748 TI - Phase II study of amrubicin, 9-amino-anthracycline, in patients with advanced non small-cell lung cancer: a West Japan Thoracic Oncology Group (WJTOG) study. AB - PURPOSE: We conducted a multicenter phase II study of amrubicin, a novel 9 aminoanthracycline, to evaluate its efficacy and safety in patients with non small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Entry requirements included cytologically or histologically proven measurable NSCLC, stage III or IV, no prior therapy, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and adequate organ function. Amrubicin was given by daily intravenous injection at 45 mg/m2/day for three consecutive days, repeated at 3 week intervals. Each patient received at least three treatment cycles. RESULTS: Sixty two patients were enrolled in this study. Of the 62 registered patients, 60 were eligible and assessable for efficacy, and 59 for toxicity. Overall response rate was 18.3% (95% confidence interval [CI], 9.5 to 30.4%) and median survival time was 8.2 months (95% CI, 6.7 to 10.4 months). Major toxicity was myelosuppression, with incidences of grade 3 or 4 toxicity of 78.0% for neutropenia, 54.2% for leukopenia, 30.5% for anemia, and 28.8% for thrombocytopenia. Non-hematological toxicities with a greater than 50% incidence were anorexia (69.5%), nausea/vomiting (55.9%), and alopecia (75.9%), but were relatively mild, with grade 3 toxicities observed in only one patient each (1.7%). CONCLUSION: Amrubicin was an active, well-tolerated agent in the treatment of NSCLC. PMID- 17351749 TI - The toxic potential of aldrin and heptachlor on Danio rerio juveniles (Cypriniformes, Cyprinidae). AB - With the objective of evaluating the effects of organochlorine pesticides (aldrin and heptachlor) on the survival, growth and gill morphology of juvenile zebrafish (Danio rerio), four partial chronic toxicity bioassays were conducted (seven days' duration) with both compounds in a semi-static system with renewal every 24 h. The results did not show any effects on the fish's survival, but did on their growth and gill morphology. Aldrin was more toxic than heptachlor, since the chronic value (CV) for growth was nearly 8.7 times less, a result confirmed by analyzing the histology of the gills, in which the changes detected were considered more severe for the former substance. In general, they were found branchial lesions of first stage, in other words, cell proliferation between the secondary lamellae, hyperplasia, lifting of respiratory epithelial cells; fusion of several secondary lamellae and dilation of blood vessels. Aneurysms (alterations of second stage) they were verified in the exposed organisms to the aldrin, which also presented about 10% of reduction in the standard length and 30% of reduction in the total weight in relation to the exposed organisms to the control. For heptachlor these values were of 8% and 25%, respectively. The intensity of the gill lesions and growth of the fish did not depend on the pesticide concentration, suggesting different modes of action of the products. PMID- 17351750 TI - Modeling and detecting potentially ruinous streaks in health expenditures. AB - The mean of a distribution of medical expenditures in an insured population can be affected significantly by the occurrence of a few high cost cases. This fact leads some organizations that hold the primary risk for the population (e.g., health plans or self-insured employers) to seek reinsurance arrangements that spread the risk of high cost cases across a broader pool. Recently, the private reinsurance market has experienced some difficulties, attributable to information asymmetries between primary risk holders and reinsurers. The disproportionate effect of a few high cost cases also has generated interest in the development of "risk-adjustment" systems that attempt to reduce the difference in health plans' unreimbursed costs either to endogenous management decisions or random chance. We discuss these issues in light of a well-known statistical result regarding the probability of "streaks" in random data. We illustrate problems that can arise and suggest methods to distinguish random streaks from systematic trends. PMID- 17351751 TI - The attribution of hostile intent in mothers, fathers and their children. AB - Child externalising symptoms are associated with a bias towards attributing hostile intent to others. We examined the role of parental attributions in the development of this hostile attribution bias in children. The parents of 134 children aged 5-7 years responded to hypothetical social scenarios examining a) their general tendency to attribute hostile intent to the ambiguous behaviour of others, and b) hostile attributions made specifically to their child. Children's own attributions of hostile intent and levels of externalising symptomatology were assessed. The results indicated that child externalising symptoms were positively associated with both a generalised tendency towards the attribution of hostile intent and child-specific hostile attributions in parents. Child externalising symptoms were themselves associated with hostile attributions made by the child. However, no direct associations were observed between parental and child attributions of hostile intent. Thus, although the results suggest a role for parental social information processing biases in the development of child externalising symptoms, a direct transmission of such biases from parent to child was not supported. PMID- 17351752 TI - Restraint and cancellation: multiple inhibition deficits in attention deficit hyperactivity disorder. AB - We used variations of the stop signal task to study two components of motor response inhibition-the ability to withhold a strong response tendency (restraint) and the ability to cancel an ongoing action (cancellation)-in children with a diagnosis of attention deficit hyperactivity disorder (ADHD) and in non-ADHD controls of similar age (ages 7-14 years). The goal was to determine if restraint and cancellation were related and if both were deficient in ADHD. The stop signal task involved a choice reaction time task (go task) which required a rapid response. The demand for inhibitory control was invoked through the presentation of a stop signal on a subset of go trials which required that the ongoing response be suspended. The stop signal was presented either concurrently with the go signal (restraint version) or after a variable delay (cancellation version). In Study 1, we compared ADHD and control children on the cancellation version of the stop task; in Study 2, we compared ADHD and controls on the restraint version. In Study 3, a subset of ADHD and control participants completed both tasks so that we could examine convergence of these dimensions of inhibition. Compared to control participants, ADHD participants showed a deficit both in the ability to cancel and to restrain a speeded motor response. Performance on the restraint version was significantly correlated with performance on the cancellation version in controls, but not in ADHD participants. We conclude that ADHD is associated with deficits in both restraint and cancellation subcomponents of inhibition. PMID- 17351754 TI - Psychometric properties of Darryl, a cartoon based measure to assess community violence-related PTSD in children. AB - OBJECTIVE: To examine the reliability and validity of Darryl, a cartoon-based measure of PTSD symptoms and a screening tool for identifying children and adolescents with a PTSD diagnosis. METHOD: Exposure to community violence, PTSD symptoms and diagnostic status were assessed in a sample of 49 children and adolescents at an urban outpatient psychiatry clinic. RESULTS: Darryl has good internal consistency for the full scale and adequate reliability for each DSM-IV PTSD symptom cluster. Darryl correlates significantly (r = 0.64, P < 0.001) with the most frequently used measure for assessing PTSD in children (CPTSD-RI). As a screening tool, Darryl has excellent sensitivity and specificity in relationship to the KID-SCID. CONCLUSIONS: In comparison to other child PTSD measures, Darryl has comparable or better psychometric properties and assesses PTSD symptoms in a more developmentally appropriate manner, especially in the domain of community violence. The value of Darryl as a screening tool remains preliminary given the limited number of diagnosed cases of PTSD in the study sample. Full scale efforts at replication are warranted. PMID- 17351755 TI - Changes in the treatment of acute psychosis in a German public hospital from 1998 to 2004. AB - INTRODUCTION: The aim of our study was to investigate antipsychotic treatment strategies in acute schizophrenic episodes in a German university hospital. METHODS: Documented pharmacological procedures in the first six weeks of acute episodes of schizophrenia in the years 1998 (n = 108), 2001 (n = 92), and 2004 (n = 94) were analyzed. Inclusion criteria were: admission voluntary and involuntary as inpatient to our acute ward with a diagnosis of F20x according to ICD 10. RESULTS: Atypical antipsychotics (AAP) were significant more frequently used in the first week of treatment in 2001 and 2004 compared to the year 1998. Switching to AAP occurred significantly earlier in 2001 and 2004 (after 7.6 +/- 7 days in 1998, 3.5 +/- 5 days in 2001 and 2.3 +/- 5 days in 2004; P < 0.002). In all three years prescription of high potent typical antipsychotics decreased during the first six weeks of treatment. Involuntary treatment (P < 0.001) and age (P = 0.001) were significantly correlated to initial prescription of AAP. Involuntary admitted patients received more often a combination of high-potent conventional high potent typical neuroleptics and AAP (48% vs. 24%, P = 0.007). CONCLUSION: Second generation atypicals are used more frequently according to current guidelines and switching from conventional medications occurs earlier. PMID- 17351756 TI - Kisspeptins and the placenta: regulation of trophoblast invasion. AB - The invasion of extravillous trophoblasts into the uterine wall is of crucial importance for placental and fetal development, and its dysregulation has been implicated in a wide spectrum of abnormal pregnancies. Mechanistically, trophoblast invasion strongly resembles the invasion of tumour cells, but differs from it by tight regulation in time and space. This regulation is accomplished by different factors including cytokines and hormones, which are produced by both fetal as well as maternal tissues i.e., placenta and uterus, respectively. Recently, products of the KiSS-1 gene (kisspeptins) have been identified to not only inhibit metastasis in various tumours, but also to repress trophoblast invasion via binding to the G protein-coupled receptor KiSS-1R. In the placenta, expression levels of kisspeptins and their receptor are highest in the first trimester in humans and at day 12.5 in rats, respectively. This coincides with the time when invasiveness peaks and invasion regulation is of central importance. Human kisspeptins are predominantly produced by the syncytiotrophoblast, whereas KiSS-1R is additionally expressed on the invading extravillous trophoblasts indicating a paracrine regulation of extravillous trophoblast invasion by the syncytiotrophoblast. In the structurally different rat placenta both KiSS-1 and its receptor are predominantly expressed by the invasive trophoblast giant cells, thus establishing an autocrine system in the invasion regulation of this trophoblast subpopulation. Amongst all kisspeptins the highly conserved kisspeptin Kp-10 has strongest invasion inhibiting effects suggesting its major role in regulation of trophoblast invasion. PMID- 17351757 TI - Grounded theory and backward mapping: exploring the implementation context for wraparound. AB - Within children's mental health, there is an increasing demand for wider implementation of wraparound and other interventions that can provide comprehensive, individualized, family-driven care. Unfortunately, implementation has proven difficult because these approaches do not necessarily flourish within traditionally organized agencies and systems. This has highlighted the need for information about how mental health agencies and systems must evolve if they are to provide a hospitable implementation environment for these interventions. A first step in developing this information is through research that advances conceptual and theoretical understanding of the impact of contextual factors on implementation. At the same time, there is an immediate need for practical information to guide decision making and policy development in settings where implementation is being undertaken. This article describes a study of wraparound implementation that used a combination of qualitative strategies to meet both of these needs simultaneously. It is argued that these strategies are particularly well suited to the study of emerging practices that reflect-and help drive transformation in mental health systems. PMID- 17351758 TI - The concept of recovery as an organizing principle for integrating mental health and addiction services. AB - Despite a range of long-standing historical, political, ideological, professional, structural, and practical barriers, there has been, and continues to be, a clear consensus that integration between mental health and addiction services is sorely needed and long overdue. This paper focuses on one dimension of the challenge of integration from among the several - the conceptual - and proposes the construct of recovery as an organizing principle for bridging the divide between the two domains. After reviewing briefly the parallel history of the two traditions and their shared need for transformation to a recovery orientation, the authors offer an integrated model of recovery for persons with co-occurring disorders. They then derive from this model the underlying values, guiding principles, key strategies, and essential ingredients of recovery oriented systems of care that comprise a common approach across both addictions and mental illness, offering a strengths-based solution to achieving integration where pathology-focused approaches have failed. PMID- 17351759 TI - Clinical follow-up of 11 Argentinian CD40L-deficient patients with 7 unique mutations including the so-called "milder" mutants. AB - CD40 ligand (CD40L) deficiency is an X-linked combined immunodeficiency characterized by impaired class switch recombination. We analyzed clinical and molecular findings in 11 Argentinian patients from seven unrelated families. The mean age at onset of symptoms was 1.1 years (0.5-3.0 years) and the 10 alive patients have a median age of 17 years. We identified two nonsense mutations, including R11X reported as a "hypomorphic" defect, four missense mutations, and one point deletion. Although R11X was associated herein with parvovirus B19 anemia and higher Igs levels as previously described, histoplasmosis and Pneumocystis jiroveci pneumonia were also present. Other so-called "milder" mutation, T254M, was present in three related patients clinically and immunologically undistinguishable from the rest of the cohort. Furthermore, 10 of the 11 patients, having heterogeneous mutations, never had persistent neutropenia, none presented Cryptosporidium sp. infection nor developed liver biliary tract disease, highlighting the debatable concept of "milder" mutations. PMID- 17351762 TI - Influence of CCR5-Delta32 genotype in Spanish population with multiple sclerosis. AB - A number of association studies have explored the relationship between the CCR5 Delta32 allele and the risk of developing multiple sclerosis (MS), with varying results. In light of the results of several studies that have analyzed the role of the allele in MS, it has been proposed that the allele is involved in the etiopathogeny of the disease. Our study revealed a statistically significant difference between the study group and the control group for the carriers of at least one deleted allele (P = 0.027). The allele was more frequent in the control group, which suggests a possible protective effect of this deletion against MS. When ethnic origin was taken into account in the same analysis, we saw that the bulk of the difference was attributable to the Basque group, although the trend was also visible in the control group. Consideration of ethnic origin is therefore essential for the analysis of our sample. CCR5-Delta32 allele distribution was higher in the Basque control population than in the Basque MS population, which suggests that it confers a protective effect against MS. Relevant values were a P value of 0.008 and an odds ratio of 0.168 (95% confidence interval, 0.038 to 0.737). PMID- 17351760 TI - Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. AB - Initially used as a replacement therapy for immunodeficiency diseases, intravenous immunoglobulin (IVIg) is now widely used for a number of autoimmune and inflammatory diseases. Considerable progress has been made in understanding the mechanisms by which IVIg exerts immunomodulatory effects in autoimmune and inflammatory disorders. The mechanisms of action of IVIg are complex, involving modulation of expression and function of Fc receptors, interference with activation of complement and the cytokine network and of idiotype network, regulation of cell growth, and effects on the activation, differentiation, and effector functions of dendritic cells, and T and B cells. PMID- 17351763 TI - RNAi-dependent and -independent antiviral phenotypes of chromosomally integrated shRNA clones: role of VASP in respiratory syncytial virus growth. AB - Stable RNA interference (RNAi) is commonly achieved by recombinant expression of short hairpin RNA (shRNA). To generate virus-resistant cell lines, we cloned a shRNA cassette against the phosphoprotein gene of respiratory syncytial virus (RSV) into a polIII-driven plasmid vector. Analysis of individual stable transfectants showed a spectrum of RSV resistance correlating with the levels of shRNA expressed from different chromosomal locations. Interestingly, resistance in a minority of clones was due to mono-allelic disruption of the cellular gene for vasodilator-stimulated phosphoprotein (VASP). Thus, pure clones of chromosomally integrated DNA-directed RNAi can exhibit gene disruption phenotypes resembling but unrelated to RNAi. PMID- 17351766 TI - Comment on: Evans JMM, Ogston SA, Emslie-Smith A, Morris AD (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930-936. PMID- 17351764 TI - The proprotein convertases are potential targets in the treatment of dyslipidemia. AB - The family of the secretory proprotein convertases (PCs) comprises seven basic amino acid (aa)-specific subtilisin-like serine proteinases known as PC1/3, PC2, furin, PC4, PC5/6, PACE4 and PC7, and two other PCs, SKI-1 (subtilisin-kexin isozyme-1)/S1P (site-1 protease) and PCSK9 (proprotein convertase subtilisin kexin 9) that cleave at nonbasic residues. Except for the testicular PC4, all the other convertases are expressed in brain and peripheral organs and play a critical role in various functions including the production of diverse neuropeptides as well as growth factors and receptors, the regulation of cellular adhesion/migration, cholesterol and fatty acid homeostasis, and growth/differentiation of progenitor cells. Some of these convertases process proteins that are implicated in pathologies, including cancer malignancies, tissue regeneration, and viral infections. The implication of some of these convertases in sterol/lipid metabolism has only recently been appreciated. SKI 1/S1P activates the synthesis of cholesterol and fatty acids as well as the LDL receptor (LDLR), whereas PCSK9 inactivates the LDLR. Moreover, furin, PC5 and/or, PACE4 inactivates endothelial and lipoprotein lipases. Humans and mice exhibiting either a gain or loss of function of PCSK9 through specific point mutations or knockouts develop hypercholesterolemia and hypocholesterolemia phenotypes, respectively. A PCSK9 inhibitor in combination with statins offers a most promising therapeutic target to treat cardiovascular disorders including dyslipidemias. Specific inhibitors/modulators of the other PCs should find novel therapeutic applications in the control of PC-regulated pathologies. PMID- 17351767 TI - Suppression of LTP-like plasticity in human motor cortex by the GABAB receptor agonist baclofen. AB - Previous experiments in slice preparations revealed that pharmacological activation of GABAB receptors down- or up-regulates long-term potentiation (LTP), depending on whether increase of GABAB receptor mediated inhibitory postsynaptic potentials or decrease of presynaptic auto-inhibition of GABAA receptor mediated inhibition predominates. The effects of GABAB receptor activation on LTP in humans in vivo are unknown. Here we show, by using transcranial magnetic stimulation, that the GABAB receptor agonist baclofen decreases paired associative stimulation induced LTP-like plasticity in human motor cortex. This suggests that increased GABAB mediated inhibitory postsynaptic potentials drive this effect, and that baclofen may have a negative impact on LTP-dependent behavioural processes such as motor learning. PMID- 17351768 TI - Adverse drug effects in elderly people -- a disparity between clinical examination and adverse effects self-reported by the patient. AB - OBJECTIVE: The trend towards polypharmacy is increasing among the elderly, and associated with this trend is an increased risk of adverse drug effects and drug drug interactions. Our objective was to assess whether drug adverse effects reported by patients are in general agreement with those identified by a physician. METHODS: We evaluated the medication of 404 randomly selected individuals aged 75 years or older by means of interviews carried out by trained nurses and examinations conducted by a physician. The medication used by these patients was recorded prior to the physician's examination and modified thereafter if considered appropriate. Adverse effects noted by the physician were compared to those self-reported by the patients. RESULTS: Almost all of the patients (98.8%) were using at least one drug, and the mean total number of drugs used was 6.5. Adverse effects were self-reported by 11.4% of the patients, whereas the physician observed apparent adverse drug effects in 24.0% of the patients. No adverse effects were reported in 53.2% of the patients. There were only seven patients that had adverse effects that were both self-reported and identified by the physician, and only four of these patients reported the same adverse effect that had been identified by the physician. CONCLUSION: There was a great disparity between the adverse effects identified by the physician and those reported by the patients themselves. Based on our results, it would appear that elderly people tend to neglect adverse drug effects and may consider them to be an unavoidable part of normal ageing. Therefore, physicians should enquire about possible adverse effects even though elderly patients may not complain of any drug-related problems. PMID- 17351769 TI - Regulation of porcine classical and nonclassical MHC class I expression. AB - Major histocompatibility complex (MHC) class I molecules comprise a family of polymorphic cell surface receptors consisting of classical 1 a molecules that present antigenic peptides and nonclassical 1 b molecules. Gene expression for human classical and nonclassical MHC class I molecules has been shown to be differentially regulated by interferon, with variation in the nucleotide sequence of promoter regions, resulting in differences in interferon inducibility and basal levels of gene transcription. In this study on porcine classical and nonclassical swine leukocyte Ag (SLA) class I molecules, we show alignments of putative regulatory elements in the promoters of the three functional classical class I genes, SLA-1, SLA-2, and SLA-3; two nonclassical 1 b genes, SLA-6 and SLA 7; and a MIC-2 gene. Promoter elements were cloned upstream from a luciferase reporter gene, and the basal and inducible activities of each were characterized by expression in Max cells, an immortalized pig cell line that responds to interferon and tumor necrosis factor alpha (TNF-alpha). All three classical class I but not nonclassical promoters responded to interferon. This was confirmed by the transactivation of SLA-1, but not SLA-7, after the co expression with interferon regulatory factors (IRFs), IRF-1, IRF-2, IRF-3, IRF-7, and IRF-9. Classical class I genes were activated by cotransfection with nuclear factor kappa B (NF-kappaB) p65 and by treatment of cells with TNF-alpha, although, unlike human promoter there was no synergistic effect with interferon. The greatest effect on classical class I promoters was coexpression with the class II transactivator (CIITA), important for constitutive transactivation. These results determine the differential regulation of porcine classical and nonclassical MHC class I and reflects their importance in antigen presentation during infection. PMID- 17351770 TI - Gene duplication, allelic diversity, selection processes and adaptive value of MHC class II DRB genes of the bank vole, Clethrionomys glareolus. AB - The generation and maintenance of allelic polymorphism in genes of the major histocompatibility complex (MHC) is a central issue in evolutionary genetics. Recently, the focus has changed from ex situ to in situ populations to understand the mechanisms that determine adaptive MHC polymorphism under natural selection. Birth-and-death evolution and gene conversion events are considered to generate sequence diversity in MHC genes, which subsequently is maintained by balancing selection through parasites. The ongoing arms race between the host and parasites leads to an adaptive selection pressure upon the MHC, evident in high rates of non-synonymous vs synonymous substitution rates. We characterised the MHC class II DRB exon 2 of free living bank voles, Clethrionomys glareolus by single-strand conformation polymorphism and direct sequencing. Unlike other arvicolid species, the DRB locus of the bank vole is at least quadruplicated. No evidence for gene conversion events in the Clgl-DRB sequences was observed. We found not only high allelic polymorphism with 26 alleles in 36 individuals but also high rates of silent polymorphism. Exceptional for MHC class II genes is a purifying selection pressure upon the majority of MHC-DRB sequences. Further, we analysed the association between certain DRB alleles and the parasite burden with gastrointestinal trichostrongyle nematodes Heligmosomum mixtum and Heligmosomoides glareoli and found significant quality differences between specific alleles with respect to infection intensity. Our findings suggest a snapshot in an evolutionary process of ongoing birth-and-death evolution. One allele cluster has lost its function and is already silenced, another is loosing its adaptive value in terms of gastrointestinal nematode resistance, while a third group of alleles indicates all signs of classical functional MHC alleles. PMID- 17351771 TI - Improved production of erythromycin A by expression of a heterologous gene encoding S-adenosylmethionine synthetase. AB - An S-adenosylmethionine synthetase (SAM-s) gene from Streptomyces spectabilis was integrated along with vector DNA into the chromosome of a Saccharopolyspora erythraea E2. Elevated production of SAM was observed in the recombinant strain Saccharopolyspora erythraea E1. The results from the bioassay showed that the titer of erythromycin was increased from 920 IU ml(-1) by E2 to approximately 2,000 IU ml(-1) by E1. High performance liquid chromatography (HPLC) analysis revealed that there was a 132% increase in erythromycin A compared with the original strain, while the erythromycin B, the main impurity component in erythromycin, was decreased by 30%. The sporulation process was inhibited, while the SAM-s gene was expressed. The addition of the exogenous SAM also inhibited sporulation and promoted an increase in erythromycin titers. PMID- 17351772 TI - Development of a 60-mer oligonucleotide microarray on the basis of benzene monooxygenase gene diversity. AB - We constructed a 60-mer oligonucleotide microarray on the basis of benzene monooxygenase gene diversity to develop a new technology for simultaneous detection of the functional gene diversity in environmental samples. The diversity of the monooxygenase genes associated with benzene degradation was characterized. A new polymerase chain reaction (PCR) primer set was designed using conserved regions of benzene monooxygenase gene (BO12 primer) and used for PCR-clone library analysis along with a previously designed RDEG primer which targeted the different types of benzene monooxygenase gene. We obtained 20 types of amino acid sequences with the BO12 primer and 40 with the RDEG primer. Phylogenetic analysis of the sequences obtained suggested the large diversity of the benzene monooxygenase genes. A total of 87 60-mer probes specific for each operational taxonomical unit were designed and spotted on a microarray. When genomic DNAs of single strains were used in microarray hybridization assays, corresponding sequences were successfully detected by the microarray without any false-negative signals. Hybridization with soil DNA samples showed that the microarray was able to detect sequences that were not detected in clone libraries. Constructed microarray can be a useful tool for characterizing monooxygenase gene diversity in benzene degradation. PMID- 17351773 TI - Role of small animal PET for molecular imaging in pre-clinical studies. PMID- 17351775 TI - Greater trochanteric epiphysiodesis. AB - In this paper, we wished to determine: (1) if a greater trochanteric epiphysiodesis (GTE) slows the growth of the greater trochanter; (2) if bone peg epiphysiodesis or screw epiphysiodesis is more effective at slowing greater trochanteric growth; and (3) if a GTE is most effective in young (<8 years) or older (>8) age. In this retrospective study, 35 children with unilateral Perthes disease underwent GTE. The height of the greater trochanter was measured radiographically at the time of surgery and at least two years after surgery. The untreated opposite side, which showed no radiographic evidence of Perthes disease, was used as a control. Epiphysiodesis was performed by using multiple drill holes and either a screw or a bone peg. Mean age at the time of surgery was 7 years (range, 3.2 to 12.2 years) and mean follow-up was 58 months (range, 24 to 104 months). We found that the growth of the greater trochanter that underwent epiphysiodesis was inhibited by 0.9 mm/year, as compared to the unaffected side (p=0.007). Greater inhibition (1.8 mm/year) was noted in children who underwent a bone peg epiphysiodesis and also, surprisingly, in those over 8 years of age. PMID- 17351774 TI - Scintigraphic techniques in primary hyperparathyroidism: from pre-operative localisation to intra-operative imaging. AB - INTRODUCTION: Primary hyperparathyroidism (PHPT) is an increasingly diagnosed disease worldwide. In most cases, PHPT is related to the presence of a solitary parathyroid adenoma (PA). Fifty percent or more of newly diagnosed PHPT patients are asymptomatic, and there is debate among endocrinologists and endocrine surgeons about whether or not such patients should be treated. LOCALIZATION: Usually, in a PHPT patient with a solitary PA that is well localised pre operatively, a parathyroidectomy with limited or minimally invasive neck exploration is offered. The diffusion of minimally invasive neck exploration procedures is a consequence of the significant improvement in the accuracy of pre operative imaging (mainly scintigraphic) techniques; these techniques have changed the surgical strategy to PHPT, from the wide traditional bilateral neck exploration to limited neck exploration. REVIEW: The present review considers developments during the past 10-15 years with regard to both the accuracy of pre operative localising imaging techniques and intra-operative minimally invasive procedures in order to provide endocrinologists and endocrine surgeons with further information about the newly available diagnostic and therapeutic tools for use in PHPT patients with a solitary PA. PMID- 17351776 TI - Recurrent pericardial effusion and pericardial tamponade in a patient with limited systemic sclerosis. AB - We describe a patient with limited systemic sclerosis who presented with a large pericardial effusion with tamponade on echocardiogram, requiring pericardiocentesis to drain 1.2 l of fluid. She had a rapid re-accumulation of pericardial fluid and subsequently required a pericardial window. Although small pericardial effusions are common in patients with systemic sclerosis it is rare to have hemodynamic compromise. Previously reported large pericardial effusions have been seen in patients with pulmonary hypertension and renal failure however these were absent in our patient. PMID- 17351777 TI - Tissue culture-induced locus-specific alteration in DNA methylation and its correlation with genetic variation in Codonopsis lanceolata Benth. et Hook. f. AB - We have reported recently that tissue culture induced a high level of genetic variation at the primary nucleotide sequence in regenerants of medicinal plant Codonopsis lanceolata. It is not known, however, whether epigenetic variation in the form of alteration in DNA methylation also occurred in these plants. Here, we investigated possible alterations in level and pattern of cytosine methylation at the CCGG sites in the same set of regenerants relative to the donor plant, by the MSAP method employing a pair of isoschizomers, HpaII and MspI, which recognize the same restriction site but are differentially sensitive to cytosine methylation at the CCGG sites. A total of 1,674 MSAP profiles were resolved using 39 primer combinations. Of these, 177 (10.5%) profiles were polymorphic among the regenerants and/or between the regenerant(s) and the donor plant, in EcoRI + HpaII or EcoRI + MspI digest but not in both, indicating alteration in cytosine methylation patterns of specific loci, though their estimated total level of methylation remained more or less the same as the donor plant. Gel blot analysis validated most of the variant MSAP profiles as bona fide alteration in methylation patterns. Correlation analysis between the MSAP data and the previously reported ISSR and RAPD data revealed significant correlations, suggesting their possible intrinsic interrelatedness. Thirty-seven typical variant MSAP profiles were isolated and sequenced, of which 5 showed significant homology to known-function genes, 2 to chloroplast sequences, whilst the rest 30 did not find a match in the database. PMID- 17351778 TI - The role of MR imaging in scaphoid disorders. AB - The scaphoid bone of the wrist is one of the most commonly fractured bones in the body. Due to its importance in the biomechanics and functionality of the wrist, it is important to depict and characterize the type of injury. Plain radiographs and scintigraphy may fail to disclose the type and severity of the injury. In patients with normal initial plain radiographs, MR imaging can discriminate occult fractures from bone bruises and may also demonstrate ligamentous disruption. MR imaging can also discriminate the proximal pole viability versus avascular necrosis secondary to previous fracture, which is important for treatment planning. Treatment of non-united fractures with vascularized grafts can be evaluated with contrast-enhanced MR imaging. Idiopathic osteonecrosis or Preiser's disease was originally described after trauma. The non-traumatic disorders of the scaphoid include post-traumatic osteoarthritis, inflammatory bone marrow edema in patients with rheumatoid arthritis, and osteomyelitis. MR imaging is helpful in all the above disorders to demonstrate early bone marrow edema, cartilage degeneration and associated subchondral marrow changes. The most commonly found tumors in the scaphoid are usually benign and include enchondroma, osteoblastoma and osteoid osteoma. MR imaging is not mandatory for the initial diagnosis, which should be based on plain X-ray findings. PMID- 17351779 TI - Microbubble ultrasound contrast agents: an update. AB - Microbubble contrast agents for ultrasound (US) have gained increasing interest in recent years, and contrast-enhanced US (CEUS) is a rapidly evolving field with applications now extending far beyond the initial improvements achieved in Doppler US. This has been achieved as a result of the safe profile and the increased stability of microbubbles persisting in the bloodstream for several minutes, and also by the availability of specialized contrast-specific US techniques, which allow a definite improvement in the contrast resolution and suppression of signal from stationary tissues. CEUS with low transmit power allows real-time scanning with the possibility of prolonged organ insonation. Several reports have described the effectiveness of microbubble contrast agents in many clinical applications and particularly in the liver, spleen, and kidneys. CEUS allows the assessment of the macrovasculature and microvasculature in different parenchymas, the identification and characterization of hepatic and splenic lesions, the depiction of septal enhancement in cystic renal masses, and the quantification of organ perfusion by the quantitative analysis of the echo signal intensity. Other fields of application include the assessment of abdominal organs after traumas and the assessment of vesico-ureteral reflux in children. Finally, tumor-targeted microbubbles make possible the depiction of specific biologic processes. PMID- 17351780 TI - Effect of computer-aided detection as a second reader in multidetector-row CT colonography. AB - Our purpose was to assess the effect of computer-aided detection (CAD) on lesion detection as a second reader in computed tomographic colonography, and to compare the influence of CAD on the performance of readers with different levels of expertise. Fifty-two CT colonography patient data-sets (37 patients: 55 endoscopically confirmed polyps > or =0.5 cm, seven cancers; 15 patients: no abnormalities) were retrospectively reviewed by four radiologists (two expert, two nonexpert). After primary data evaluation, a second reading augmented with findings of CAD (polyp-enhanced view, Siemens) was performed. Sensitivities and reading time were calculated for each reader without CAD and supported by CAD findings. The sensitivity of expert readers was 91% each, and of nonexpert readers, 76% and 75%, respectively, for polyp detection. CAD increased the sensitivity of expert readers to 96% (P = 0.25) and 93% (P = 1), and that of nonexpert readers to 91% (P = 0.008) and 95% (P = 0.001), respectively. All four readers diagnosed 100% of cancers, but CAD alone only 43%. CAD increased reading time by 2.1 min (mean). CAD as a second reader significantly improves sensitivity for polyp detection in a high disease prevalence population for nonexpert readers. CAD causes a modest increase in reading time. CAD is of limited value in the detection of cancer. PMID- 17351782 TI - Sacral parasite with histopathological features of an unequally conjoined twin. AB - A sacral parasite is a rare congenital anomaly classified etiologically as duplicitas asymmetros, where the parasitic mass is regarded as the tissue remnants of an unequally conjoined twin. We, herein, report a case of a sacral parasitic mass found in a female neonate. A huge sacral mass was found at 30 weeks of gestation by fetal ultrasonography. The fetus was delivered by a Caesarean operation at 37 weeks and 6 days of gestation. The alpha-fetoprotein (AFP) level was 174,640 ng/ml. The mass separated by an operation on the day after her birth, contained structures similar to imperfect limbs and backbone. A variety of tissue and organs having derived from three germ layers were identified within the mass and showed a tendency to be highly differentiated. Even though a large proportion of the central nervous system tissue showed immature and dysplastic features, there were no evidences suggesting the presence of neoplasm. The infant has shown normal growth and is doing well without a recurrence of the sacral mass or any elevation in the serum AFP level during the12-month follow-up. We therefore believe that the present case should be considered a sacral parasite, rather than a sacrococcygeal teratoma. Although it should be recognized that such sacral parasite is very rare, this case provides further information that can be useful for diagnosis. PMID- 17351783 TI - Mesorectum, is it an appropriate term? PMID- 17351781 TI - Urinary tract injuries in patients with multiple trauma. AB - This article mainly reviews urinary tract injuries in patients with multiple trauma. Approximately 10% of all traumatic injuries resulting from an external force will involve the genitourinary system. The article discusses mechanisms of injury, diagnosis, and therapeutical approaches for renal, ureteral, bladder, and urethral trauma. Due to the complexity of such injuries--despite several attempts to provide a standard strategy in trauma patients with urinary tract involvement- an individual and patient-specific-therapeutic approach is mandatory in most cases. However, the availability of classified guidelines may help the surgeon to reach the most accurate decision. Because of the similarity of American and European guidelines on urological trauma, this article adapts injury severity scales and classification from the American Association for the Surgery of Trauma. PMID- 17351784 TI - Parabolic flight experience is related to increased release of stress hormones. AB - Numerous studies have shown significant effects of weightlessness on adaptational processes of the CNS, cardiovascular and/or muscular system. Most of these studies have been carried out during parabolic flights, using the recurring 20 s of weightlessness at each parabola. Although some of these studies reported on potential influences not only of weightlessness but also of the stressful situation within a parabolic flight, especially provoked by the ongoing changes between 1.8, 1 and 0 G, so far there seems to be only marginal information about objective parameters of stress evoked by parabolic flights. By collecting blood samples from a permanent venous catheter several times during parabolic flights, we were able to show an increase of prolactin, cortisol and ACTH in the course of a 120 min flight. We conclude, therefore, that previous reported effects of weightlessness on adaptational processes may be affected not only by weightlessness but also by the exposure to other stressors experienced within the environment of a Zero-G airbus. PMID- 17351785 TI - Physiological costs and temporo-spatial parameters of walking on a treadmill vary with body weight unloading and speed in both healthy young and older women. AB - Walking on a treadmill with Body Weight Unloading (BWU), which has been successfully used on patients with neurological conditions, may also be used as a training tool to increase walking speed in healthy individuals. We hypothesised that BWU enables individuals to walk at a faster speed on a treadmill than they would do in normal gravity conditions without increasing their effort and with an increase in both stride length (SL) and stride frequency (SF). Oxygen uptake, heart rate (HR), SL and SF of six older women (mean +/- SD; 70 +/- 4 years) and six young women (26 +/- 3 years) were measured during treadmill walking at three self-selected speeds (comfortable, slow and fast) and three different percentages of BWU (0, 20 and 40%). No significant differences were found between the groups in any self-selected walking speeds and any of the other variables. The combined data of the two groups showed that walking energy cost per unit of time (WECt) and HR at fast speed with 40% of BWU (258 +/- 60 J kg(-1) min(-1) and 95 +/- 15 beats min(-1), respectively) were similar to those measured at comfortable speed with no BWU (273 +/- 47 J kg(-1) min(-1) and 101 +/- 16 beats min(-1), respectively). Also SL and SF increased significantly with speed (P < 0.017) at any given percentage of BWU. The results suggest that 40% of BWU enables both young and older women to walk at a faster speed on a treadmill without increasing their effort and with an increase in both SL and SF. PMID- 17351786 TI - Phototransduction in ganglion-cell photoreceptors. AB - A third class of photoreceptors has recently been identified in the mammalian retina. They are a rare cell type within the class of ganglion cells, which are the output cells of the retina. These intrinsically photosensitive retinal ganglion cells support a variety of physiological responses to daylight, including synchronization of circadian rhythms, modulation of melatonin release, and regulation of pupil size. The goal of this review is to summarize what is currently known concerning the cellular and biochemical basis of phototransduction in these cells. I summarize the overwhelming evidence that melanopsin serves as the photopigment in these cells and review the emerging evidence that the downstream signaling cascade, including the light-gated channel, might resemble those found in rhabdomeric invertebrate photoreceptors. PMID- 17351787 TI - Mir1-CP, a novel defense cysteine protease accumulates in maize vascular tissues in response to herbivory. AB - When lepidopteran larvae feed on the insect-resistant maize genotype Mp708 there is a rapid accumulation of a defensive cysteine protease, Maize insect resistance 1-cysteine protease (Mir1-CP), at the feeding site. Silver-enhanced immunolocalization visualized with both light and transmission electron microscopy was used to determine the location of Mir1-CP in the maize leaf. The results indicated that Mir1-CP is localized predominantly in the phloem of minor and intermediate veins. After 24 h of larval feeding, Mir1-CP increased in abundance in the vascular parenchyma cells and in the thick-walled sieve element (TSE); it was also found localized to the bundle sheath and mesophyll cells. In situ hybridization of mRNA encoding Mir1-CP indicated that the primary sites of Mir1-CP synthesis in the whorl are the vascular parenchyma and bundle sheath cells. In addition to the phloem, Mir1-CP was also found in the metaxylem of the leaf and root. After 24 h of foliar feeding, the amount of Mir1-CP in the root xylem increased and it appeared to move from xylem parenchyma into the root metaxylem elements. The accumulation of Mir1-CP in maize vascular elements suggests Mir1-CP may move through these tissues to defend against insect herbivores. PMID- 17351788 TI - Reciprocal influence of ethylene and gibberellins on response-gene expression in Arabidopsis thaliana. AB - The complexity of hormonal responses and their functional overlap support the presence of an intensive cross-talk between hormone signalling pathways. A detailed analysis of responses induced by ethylene and gibberellin (GA) in a GA insensitive mutant (gai), an ethylene-resistant mutant (etr1-3), the gai etr1-3 double-mutant, and in wild-type Arabidopsis thaliana plants, revealed multiple interactions between ethylene and GA signal transduction pathways. Ethylene insensitive mutants and wild-type plants treated with 1-methylcyclopropene (1 MCP), an ethylene perception inhibitor, displayed a stronger responsiveness of genes differentially regulated by GA. In addition, microarray-analysis showed that the GA-response in an ethylene-insensitive background is different from that in the wild-type, confirming the importance of ethylene in a plant's response towards GA. In this paper, we present a number of genes with an altered response pattern as a direct consequence of cross-talk between ethylene and GA. PMID- 17351789 TI - Endogenous orienting modulates the Simon effect: critical factors in experimental design. AB - Responses are faster when the side of stimulus and response correspond than when they do not correspond, even if stimulus location is irrelevant to the task at hand: the correspondence, spatial compatibility effect, or Simon effect. Generally, it is assumed that an automatically generated spatial code is responsible for this effect, but the precise mechanism underlying the formation of this code is still under dispute. Two major alternatives have been proposed: the referential-coding account, which can be subdivided into a static version and an attention-centered version, and the attention-shift account. These accounts hold clear-cut predictions for attentional cuing experiments. The former would assume a Simon effect irrespective of attentional cuing in its static version, whereas the attention-centered version of the referential-coding account and the attention-shift account would predict a decreased Simon effect on validly as opposed to invalid cued trials. However, results from previous studies are equivocal to the effects of attentional cuing on the Simon effect. We argue here that attentional cueing reliably modulates the Simon effect if some crucial experimental conditions, mostly relevant for optimizing attentional allocation, are met. Furthermore, we propose that the Simon effect may be better understood within the perspective of supra-modal spatial attention, thereby providing an explanation for observed discrepancies in the literature. PMID- 17351790 TI - Occurrence of Camallanus cotti in greatly diverse fish species from Danjiangkou Reservoir in central China. AB - Two thousand four hundred fifty-eight fish comprised of 53 species were captured in the Danjiangkou Reservoir, in the northwestern part of Hubei Province, central China during 2004, to examine Camallanus cotti infections. We found that 19 cypriniform, 3 siluriforme, and 4 perciforme fishes were infected by the nematode. Our study revealed the species, Hemiculter bleekeri bleekeri, Culter oxycephaloide, Pseudolaubuca sinensis, Acanthobrama simony, Mylopharyngodon piceus, Ctenopharyngodon idella, Gnathopogon imberbis, G. argentatus, Saurogobio dabryi, S. dumerili, Gobiobotia ichangensis, Liobagrus marginatoides, and Ctenogobius shennongensis as new hosts of the worm. The number and range of fish host species found in this survey were much greater than any of the previous investigations. The mean prevalence, prevalence, mean abundance, and intensity of infection varied in different fish species, indicating a possible host preference. Moreover, we suggest that this nematode is a native parasite of cypriniform fishes in China, perhaps initially in the reaches of the Yangtze River. PMID- 17351791 TI - Effects of species richness and elevated carbon dioxide on biomass accumulation: a synthesis using meta-analysis. AB - Magnitude of growth enhancement by elevated CO(2) in a plant assemblage is dependent on a number of biotic and abiotic factors, including species richness. In this meta-analysis, we examined effects of elevated CO(2) on plant biomass accumulation in single- (populations) and multi-species (communities) assemblages. The primary objectives were to statistically synthesize the voluminous CO(2) studies conducted so far and to assess the collective response of plant growth to elevated CO(2) as affected by species richness. Our analysis showed that biomass enhancement by higher CO(2) was consistently lower in communities than in populations. For example, total plant biomass (W(T)) increased only 13% in communities compared to 30% in populations in response to elevated CO(2) across all studies included in this synthesis. Above- and below ground biomass responded similarly as W (T) to elevated CO(2) and species richness. Smaller growth enhancement by CO(2) was found in communities consisting of species of different growth forms (woody vs. herbaceous species) or functional groups (legumes vs. non-legumes). This pattern was consistent across three major classes of facilities (closed, semi-open and open systems) used to manipulate CO(2) concentrations. An analysis of free-air CO(2) enrichment studies revealed that the population-community difference in growth enhancement by higher CO(2) was also dependent on the rate of N addition. Populations responded more than communities only when soil was amended with N. From the CO(2) studies synthesized in this meta-analysis, it is obvious that the collective growth responsiveness to elevated CO(2) will be lower in communities than in populations. We hypothesize that resource usurpation, i.e., competitive compartmentation of growth-limiting resources by less responsive species, may be important in determining growth response to elevated CO(2) in a community and is one of the reasons responsible for the lower biomass enhancement by elevated CO(2) in communities, as found in this synthesis. PMID- 17351792 TI - Amphibian survival, growth and development in response to mineral nitrogen exposure and predator cues in the field: an experimental approach. AB - Mineral nitrogen (N) has been suggested as a potential factor causing declines in amphibian populations, especially in agricultural landscapes; however, there is a question as to whether it remains in the water column long enough to be toxic. We explored the hypothesis that mineral N can cause both lethal and sublethal toxic effects in amphibian embryos and larvae in a manipulative field experiment. We sampled 12 ponds, fertilizing half with ammonium nitrate fertilizer early in the spring, and measured hatching, survival, development, growth, and the incidence of deformities in native populations of wood frog (Rana sylvatica) and eastern tiger salamander (Ambystoma tigrinum tigrinum) embryos and larvae held in in situ enclosures. We found that higher ammonium concentrations negatively affect R. sylvatica more strongly than A. tigrinum. R. sylvatica tended to have lower survival as embryos and young tadpoles, slowed embryonic development, and an increased proportion of hatchlings with deformities at experimentally elevated ammonium. A. tigrinum did not experience significantly reduced survival, but their larval development was slowed in response to elevated ammonium and the abundance of large invertebrate predators. Variable species susceptibility, such as that shown by R sylvatica and A. tigrinum, could have large indirect effects on aquatic community structure through modification of competitive or predator prey relationships. Ammonium and nitrate + nitrite concentrations were not correlated with other measures that might have affected amphibians, such as pH, pond area, depth, or vegetation. Our results highlight the potential importance of elevated ammonium on the growth, development and survival of amphibians, especially those that breed in surface waters receiving anthropogenic N inputs. PMID- 17351793 TI - Influence of temporal heterogeneity in nitrogen supply on competitive interactions in a desert shrub community. AB - Soil nutrients in arid systems are supplied to plants in brief pulses following precipitation inputs. While these resource dynamics have been well documented, little is known about how this temporal heterogeneity influences competitive interactions. We examined the impacts of the temporal pattern of N supply on competitive intensity and ability in an N-limited desert shrub community. At our field site, the three codominant shrubs, Atriplex confertifolia, A. parryi, and Sarcobatus vermiculatus, differ in seasonal growth patterns, with A. confertifolia and S. vermiculatus achieving higher growth rates earlier in the growing season than A. parryi. We predicted that these timing differences in maximum growth rate may interact with temporal variation in N supply to alter competitive abilities over time. Seedlings of the two Atriplex species were planted either individually in field plots or as target plants surrounded by neighbor seedlings. After one year of establishment, the same amount of (15)N was applied to plots either as early spring pulses, mid spring pulses or continuously through the second growing season. Competitive effects were observed under continuous and pulsed N supply. Averaged across all target-neighbor treatments, competitive intensity was approximately 1.8-fold greater when N was pulsed compared to when N was supplied continuously, but overall, the outcome of competitive interactions was not influenced by N pulse timing. While the timing of resource supply did not differentially influence the competitive abilities of coexisting species in this system, the temporal pattern of resource supply did alter the intensity of competitive interactions among species. While additional studies in other systems are needed to evaluate the generality of these results, this study suggests that competitive intensity may not necessarily be a direct function of productivity or resource availability as traditionally assumed. Instead, the intensity of competitive interactions in resource-poor systems may depend upon the temporal pattern of resource supply. PMID- 17351794 TI - Timing of dispersal: effect of ants on aphids. AB - Mutualists can affect many life history traits of their partners, but it is unclear how this translates into population dynamics of the latter. Ant-aphid associations are ideal for studying this question, as ants affect aphids, both positively (e.g., protection against natural enemies) and negatively (e.g., reduction of potential growth rates). The unresolved question is whether these effects, which have been observed at the level of individuals and under controlled environmental conditions, have consequences at the population level. On estimating aerial aphid populations by using weekly suction trap data spanning up to 22 years from different locations in France, we show that in ant-attended aphid species long-distance dispersal occurs significantly later, but that the year-to-year changes in the peak number of migrants are not significantly lower than for non-attended aphids. Host alternation had the same retarding effect on dispersal as ant attendance. We discuss the delay in the timing of dispersal in ant-attended aphids, and potential costs that arise in mutualistic systems. PMID- 17351795 TI - Positive indirect effect of tadpoles on a detritivore through nutrient regeneration. AB - In aquatic food webs consumers can affect other members of the web by releasing nutrients as a result of their feeding activity. There is increasing evidence of these positive effects on primary producers, but such nutrient regeneration can also affect detritivores, by favoring the activities of detritus-associated microbes. We examined the effects of nutrient regeneration by tadpoles on leaf eating detritivores under laboratory conditions. We fed four species of tadpoles three different food items (leaf litter, algae, and sludgeworms). We then conditioned terrestrial dead leaves with water from reared tadpoles (treatments) or food items alone (controls), and compared the C:N ratios of the conditioned leaves and the growth of the isopod Asellus hilgendorfii fed on the conditioned leaves. Tadpole feeding activity reduced the C:N ratio of conditioned leaves, and the effect was greatest when tadpoles were fed algae. Isopod growth rates were often higher when they were fed the litter conditioned with water from reared tadpoles. Thus, nutrient regeneration by tadpoles had a positive indirect effect on detritivores by enhancing leaf quality. Tadpoles often occur in nutrient limited habitats where leaf litter is the major energy source, and their facilitative effects on leaf-eating detritivores may be of great significance in food webs by enhancing litter decomposition. PMID- 17351796 TI - Host habitat patchiness and the distance decay of similarity among gastro intestinal nematode communities in two species of Mastomys (southeastern Senegal). AB - Beta-diversity, or how species composition changes with geographical distance, has seldom been studied for different habitats. We present here quantitative estimates of the relationship between geographic distance and similarity of parasitic nematode communities in two closely related rodent host species that live in habitats with very different spatial configurations. In southeastern Senegal Mastomys natalensis lives exclusively inside human villages whereas M. erythroleucus is continuously distributed outside villages. Both host species and their gastro-intestinal nematodes were sampled on the same spatial scale. Beta diversity was found to be higher in parasite communities of M. erythroleucus than in those of M. natalensis, and significantly related to geographic distance in this first species. Even on the local spatial scale studied, host dispersal limitation, and stochastic events, may affect species turnover in nematode communities of M. erythroleucus. In M. natalensis, no relationship was found between geographic distance and nematode community similarity, however, suggesting low host dispersal rates between habitat patches. Together with previous population genetic results, this study illustrates the need for different approaches with regard to dispersal in natural populations and its effect on biodiversity. PMID- 17351797 TI - Multi-trophic effects of ungulate intraguild predation on acorn weevils. AB - Predators and parasitoids may contribute to controlling the population sizes of phytophagous insects, and this has been shown to benefit plants. Phytophagous insects may also be killed by other herbivores (intraguild predation), usually larger-sized vertebrates that ingest insects accidentally while feeding on common food sources. We studied the intraguild predation on acorn weevils by ungulates and assessed the consequences for weevil populations. Infested acorns are prematurely abscised and the weevil larvae finish their development inside the acorns after being dropped. Our results show that weevil larvae were killed by ungulates eating the infested acorns on the ground. Ungulates did not discriminate between infested and sound acorns, and the probability of a larva being incidentally eaten was inversely related to acorn availability. Thus, predation risk was enhanced by the premature drop of infested acorns when acorn availability on the ground was low. Predation rates on infested acorns were much higher where ungulates were present, and acorn infestation rates were significantly lower. However, ungulates did not provide the oaks any net benefit, since the reduction of infestation rates was not enough to compensate for the large amounts of sound acorns eaten by ungulates. Seed predation is usually studied as a progressive loss of seeds by pre- and post-dispersal predators, but the interactions between them are usually not considered. We show that intraguild predation on insects by large ungulates had an effect on the structure of the foraging guild, as the proportion of acorns predated by insects decreased; however, replicating the same experimental design in different ecological scenarios would increase the strength of these results. In conclusion, the present study shows the importance of considering the multi-trophic interactions between seed predators in order to have a complete picture of granivory. PMID- 17351798 TI - In memory of Dr. Johannes Brodehl, born 20 October 1931 and died 2 September 2006. PMID- 17351799 TI - The M-ANNHEIM classification of chronic pancreatitis: introduction of a unifying classification system based on a review of previous classifications of the disease. AB - BACKGROUND: Several classification systems of chronic pancreatitis have been proposed to provide a basis for treatment and research. All of these previous classifications were designed at the height of pancreatic research of their respective times; thus, each represented the most current knowledge available to pancreatologists at the time. However, none of these classifications provide simultaneously a simple standardized system for the clinical classification of chronic pancreatitis according to etiology, clinical stage, and severity of the disease, nor are they consistently useful for directing clinical practice and comparing interinstitutional data. Thus, we aimed to develop a new classification system of chronic pancreatitis to provide a framework for studying the interaction of various risk factors on the course of the disease. METHODS: We reviewed the literature on the clinical course of all different forms of chronic pancreatitis, and we reviewed all previous classification systems of the disease. This approach provided a basis for the development of a new and unifying classification of chronic pancreatitis. RESULTS: We established the M-ANNHEIM multiple risk factor classification system based on the current knowledge of acute and chronic pancreatitis. This classification allows patients to be categorized according to the etiology, clinical stage, and severity of their disease. The severity of pancreatic inflammation was assessed using a scoring system that takes into account the clinical symptoms and treatment options of chronic pancreatitis. Finally, four hypothetical patients were categorized according to the M-ANNHEIM classification system to provide examples of its applicability in clinical practice. CONCLUSIONS: The M-ANNHEIM multiple risk factor classification system is simple, objective, accurate, and relatively noninvasive, and it incorporates etiology, different stages of the disease, and various degrees of clinical severity. This new classification system will be helpful for investigating the impact and interaction of various risk factors on the course of the disease and will facilitate the comparison and combination of interinstitutional data. PMID- 17351800 TI - Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer. AB - BACKGROUND: Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1)-MMP, TIMP-1, and TIMP-2 in biopsy tissues of gastric cancer, and the correlation between their expression and clinicopathological parameters. METHODS: Biopsy specimens from 66 patients with gastric carcinoma were available for this study. To determine the expression of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out on tumor and normal tissues, respectively, sampled during diagnostic gastroscopic examination. Immunohistochemical staining of representative samples using monoclonal antibody directed against MT1-MMP was done, and the clinicopathological variables were reviewed retrospectively. RESULTS: The expression level of MMPs and TIMPs was evaluated using the tumor : normal (T/N) ratios of MMPs and TIMPs. The T/N ratio of MT1-MMP mRNA showed a significant correlation with lymph node metastasis and tumor stage (P < 0.05). The other RT PCR data of MMP-2, MMP-9, TIMP-1, and TIMP-2 did not show any significant correlation with clinicopathological parameters. Immunohistochemistry for MT1-MMP showed a positive immunoreaction in gastric adenocarcinoma and negative staining in normal mucosa. CONCLUSIONS: The correlation between the increased expression of MT1-MMP and clinicopathological variables reflects a role in predicting the aggressive behavior of gastric cancer. Because an RT-PCR assay can be performed on biopsy specimens obtained before surgery, an evaluation of MT1-MMP expression in biopsy specimens by RT-PCR may provide useful preoperative information on tumor aggressiveness. PMID- 17351801 TI - Effects of alpha-linolenic acid on colonic secretion in rats with experimental colitis. AB - BACKGROUND: Few studies have specifically examined the effects of n-3 polyunsaturated fatty acids (PUFAs) on intestinal water and ion secretion in ulcerative colitis (UC). The aim of this study was to examine the contribution of prostaglandins (PGs) and leukotrienes (LTs) to mucosal secretion in intestines with UC and to evaluate the effect of dietary n-3 PUFAs on diarrhea in UC. METHODS: We measured the short-circuit current (Isc), using the Ussing chamber method, and fatty acid composition in the colonic mucosa of rats with dextran sulfate sodium (DSS)-induced experimental colitis. The DSS-treated rats were fed either a perilla oil-enriched diet (perilla group) or a soybean oil-enriched diet (soybean group); a control group did not undergo DSS administration. RESULTS: The bradykinin-stimulated DeltaIsc in the soybean and perilla groups was significantly higher than that in the control group. The mucosal level of arachidonic acid in the perilla group was significantly lower than that in the soybean group. The mucosal levels of alpha-linolenic acid and EPA in the perilla group were significantly higher than those in the soybean group. The bradykinin stimulated DeltaIsc was significantly suppressed after pretreatment with indomethacin in both the soybean and perilla groups, and was also significantly reduced in both groups after pretreatment with AA861. The suppression of bradykinin-stimulated DeltaIsc by the addition of AA861 was significantly higher in the perilla group than in the soybean group. CONCLUSIONS: Our results suggest that supplementation with alpha-linolenic acid, in combination with a lipoxygenase inhibitor, could suppress the increase in Cl- secretion in patients with UC. PMID- 17351802 TI - Pancreas divisum does not modify the natural course of chronic pancreatitis. AB - BACKGROUND: Pancreas divisum is the most common congenital variant of the pancreas; however, its clinical significance remains controversial. The purpose of our study was to determine the role of pancreas divisum in the development of chronic pancreatitis. METHODS: We compared the clinical presentation, morphological findings, and course of disease of 30 patients with chronic pancreatitis associated with pancreas divisum (there was coexisting chronic alcohol abuse in 18 cases) to those of 57 patients with chronic pancreatitis and no evidence of pancreas divisum (15 with nonalcoholic pancreatitis and 42 with alcoholic pancreatitis). RESULTS: Sex distribution, age at onset of disease, clinical presentation, course of disease, and frequency of complications were not affected by the presence of pancreas divisum. Although the etiology of pancreatitis in patients with pancreas divisum may be attributed to impaired drainage of the majority of the gland through the minor papilla, we observed a relatively low frequency of isolated dorsal duct involvement in our patients irrespective of alcohol use (25% and 28% in patients with and without a history of alcohol abuse, respectively). However, involvement of the ventral duct was commonly observed (75% and 72%, respectively). CONCLUSIONS: The presence of pancreas divisum in our study did not modify the natural course of chronic nonalcoholic or alcoholic pancreatitis. Pancreas divisum is not likely to play a dominant role in the etiopathogenesis of chronic pancreatitis. PMID- 17351803 TI - Adenovirus-mediated p53 gene transfer sensitizes hepatocellular carcinoma cells to heavy-ion radiation. AB - BACKGROUND: The purpose of this study was to investigate whether adenovirus mediated p53 transfer could sensitize hepatocellular carcinoma to heavy-ion irradiation. METHODS: HepG2 cells were preexposed to a (12)C(6+) beam, and then infected with replication-deficient adenovirus recombinant vectors containing human wild-type p53 (AdCMV-p53) ((12)C(6+) irradiation + AdCMV-p53 infection). The survival fraction was determined by clonogenic assay. The cell cycle, cell apoptosis, and p53 expression were monitored by flow cytometric analysis. RESULTS: p53 expression in (12)C(6+) irradiation + AdCMV-p53 infection groups was markedly higher than that in (12)C(6+) irradiation only groups (P < 0.05), suggesting that the preexposure to the (12)C(6+) beam promoted the expression of exogenous p53 in HepG2 cells infected with AdCMV-p53 only. The G(1)-phase arrest and cell apoptosis in the (12)C(6+) irradiation + AdCMV-p53 infection groups were significantly more than those in the (12)C(6+) irradiated groups (P < 0.05). The survival fractions of the (12)C(6+) irradiation + AdCMV-p53 infection groups decreased by 30%-49% compared with those of the (12)C(6+) beam-irradiated only groups (P < 0.05). CONCLUSIONS: Adenovirus-mediated p53 gene transfer can promote G(1)-phase arrest and cell apoptosis, thus sensitizing hepatocellular carcinoma cells to heavy-ion irradiation. PMID- 17351804 TI - Mild ERCP-induced and non-ERCP-related acute pancreatitis: two distinct clinical entities? AB - BACKGROUND: The aim of this study was to evaluate the hypothesis that mild endoscopic retrograde cholangiopancreatography (ERCP)-induced acute pancreatitis (AP) runs a distinctly shorter clinical course compared with mild attacks caused by other etiological factors. METHODS: ERCP-induced AP was defined as the persistence of postprocedure abdominal pain requiring analgesia for at least 24 h in association with hyperamylasemia of more than three times the normal value. Among 2552 patients who had undergone ERCP between 1996 and 2002 in two different hospitals, mild AP developed after "elective" ERCP in 48 (group I). Among a random sample of 10% of 700 patients admitted with AP to both hospitals during the same study period, 58 had mild non-ERCP-related AP (group II). Results shown are medians. RESULTS: Patients in group I had significantly shorter durations of pain (55 vs. 114 h, P < 0.0001), analgesic intake (56 vs.93 h, P = 0.007), and intravenous hydration (48 vs. 80 h, P < 0.0001), a lower opiate analgesic requirement (58 mg morphine equivalent vs. 100 mg, P = 0.001), a shorter time to resumption of oral diet (3 vs. 5 days, P < 0.0001), and a shorter hospital stay (4 vs. 7 days, P < 0.0001) than patients in group II. CONCLUSIONS: The current definitions of ERCP-induced AP select a cohort of patients whose mild attacks run a significantly shorter and milder course than non-ERCP-related mild attacks. A new consensus definition of ERCP-induced AP that describes attacks of similar clinical course is needed. PMID- 17351805 TI - The cost-effectiveness of universal vaccination of children against hepatitis A in Argentina: results of a dynamic health-economic analysis. AB - BACKGROUND: Socioeconomic improvements can reduce levels of endemic hepatitis A, but conversely increase the burden of disease. Routine childhood vaccination can rapidly control hepatitis A infection rates through the induction of herd immunity, although such programs can be costly. METHODS: We evaluated the healthcare benefits and cost-effectiveness of a routine childhood vaccination program against hepatitis A in Argentina, using a dynamic model that incorporated the changing epidemiology of infection and the impact of vaccine-induced herd immunity. Demographic, disease, and economic data from Argentina were used where available. RESULTS: At 95% coverage, the program would reduce the number of hepatitis A infections by 352,405 annually, avoiding 121,587 symptomatic cases and 428 deaths. Substantial healthcare benefits were also observed with vaccination coverage as low as 70%, which would prevent 295,826 infections. Economically, the program would save 23,989,963 US$ annually at 95% coverage, equivalent to 3,429 US$ per life-year gained. The program remained cost-saving in response to variation in factors, including disease-related costs, discount rate, herd immunity level, and rate of decrease of force of infection. The break-even cost per vaccine dose for the society was 25 US$ in the base-case, more than three times the current public cost of 7 US$ per dose. CONCLUSIONS: Routine childhood vaccination against hepatitis A showed both health benefits and robust economic benefits in this analysis, supporting the recent decision of the Argentine government to implement such a program. PMID- 17351806 TI - Comparison between ulinastatin and gabexate mesylate for the prevention of post endoscopic retrograde cholangiopancreatography pancreatitis: a prospective, randomized trial. AB - BACKGROUND: It has been reported that the administration of ulinastatin, gabexate mesylate, or somatostatin may be effective in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, few randomized trials of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis have been reported. The aim of this study was to compare the efficacy of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis. METHODS: Sixty-eight patients who underwent diagnostic ERCP at our hospital were divided at random by computer-generated randomization into an ulinastatin group (n = 34) and a gabexate group (n = 34). Each patient received a continuous intravenous infusion of ulinastatin (150,000 units) or gabexate mesylate (600 mg), beginning 60-90 min before the ERCP and continuing until 22 h after the ERCP. The primary endpoint was the incidence of post-ERCP pancreatitis, and the secondary endpoints were the incidences of hyperenzymemia and pain. RESULTS: The overall incidence of post-ERCP pancreatitis was 2.9% (two patients), comprising one patient in the ulinastatin group and one patient in the gabexate group (2.9% vs 2.9%, respectively). Neither of these two patients developed severe pancreatitis. There were no significant differences in the serum levels of pancreatic enzymes or in the levels of pain between the two groups. CONCLUSIONS: There was no clinical difference between the effect of preventive administration of ulinastatin and that of gabexate mesylate on the incidence of post-ERCP pancreatitis. Ulinastatin may be equivalent in efficacy to gabexate for reducing the incidence of post-ERCP pancreatitis. PMID- 17351807 TI - A male patient with severe acute hepatitis who was domestically infected with a genotype H hepatitis B virus in Iwate, Japan. AB - Although all eight genotypes of hepatitis B virus (HBV) strains are circulating in Japan, no cases of acute hepatitis with foreign HBV strains of genotype H have thus far been reported in Japan. Here, we report a 35-year-old Japanese patient with severe acute hepatitis who was domestically infected with genotype H HBV. On admission, he had a high HBV load of 1.0 x 10(9) copies/ml, elevated levels of total bilirubin (7.0 mg/dl) and alanine aminotransferase (3606 IU/l), and reduced prothrombin activity of 39.0%. The HB-JAIW05 isolate obtained in the present study was composed of 3215 nucleotides and had the highest similarity of 99.7% with the reported genotype H HBV isolate recovered from a Japanese blood donor. The HB-JAIW05 isolate had neither precore (A1896) nor core promoter (T1762/A1764) mutations. However, upon comparison with the consensus sequence of ten reported HBV isolates of the same genotype, the HB-JAIW05 isolate had 17 nucleotide substitutions including five missense mutations in the P gene, which may be related to vigorous replication of HBV in this case. He had no history of traveling abroad, but had had extramarital sexual contact with two Japanese women living in Iwate, Japan, 2 weeks and 2 months before the disease onset, respectively. Our results suggest that rare HBV genotypes such as H may be spreading in Japan via sexual contact. Further molecular epidemiological studies on HBV to clarify the exact changing profiles of de novo HBV infection in Japan in relation to genotype and genomic variability are warranted. PMID- 17351808 TI - Two cases of hepatopulmonary syndrome with improved liver function following long term oxygen therapy. AB - Hepatopulmonary syndrome (HPS) is a complication of liver disease that is characterized by hypoxemia and intrapulmonary vascular dilatations. The only established therapy for this disorder is liver transplantation. Here, we report two patients (a 63-year-old woman and a 72-year-old man) with HPS associated with hepatitis C virus-related cirrhosis. We gave the patients low-dose oxygen supplementation to improve their respiratory symptoms. Surprisingly, their liver function improved from Child Pugh class C to class A, and ascites disappeared after a year of oxygen supplementation. We believe that long-term oxygen therapy contributed to the improvement of liver function in these two cases. Long-term oxygen therapy might offer a new therapeutic approach to improve liver function in patients with cirrhosis with hypoxemia. PMID- 17351809 TI - A case of lymphoepithelioma-like carcinoma of the colon with ulcerative colitis. AB - Follow-up colonoscopy of a 25-year-old Japanese man with ulcerative colitis (UC) who had undergone endoscopic mucosal resection twice for early colon cancers revealed the presence of a new 1.5-cm-diameter tumor in the sigmoid colon. It was diagnosed by preoperative biopsy as a poorly differentiated adenocarcinoma. Sigmoidectomy was performed, and the pathological findings revealed lymphoepithelioma-like carcinoma (LEC). In situ hybridization to detect Epstein Barr virus (EBV)-encoded small RNAs showed positive signals in stromal lymphocytes, but weak signals in the tumor cells. The association between EBV and LEC was obscure in this case. Unlike typical UC-mediated colon cancers, the lesion was poorly differentiated, and negative for p53 signals immunohistochemically. These findings may hint at a novel mechanism of carcinogenesis in UC-mediated colorectal cancer. PMID- 17351810 TI - Long-term nutritional assessment and quality of life in patients with cirrhosis taking a late evening snack. PMID- 17351811 TI - Response of estuarine biofilm microbial community development to changes in dissolved oxygen and nutrient concentrations. AB - The information content and responsiveness of microbial biofilm community structure, as an integrative indicator of water quality, was assessed against short-term changes in oxygen and nutrient loading in an open-water estuarine setting. Biofilms were grown for 7-day periods on artificial substrates in the Pensacola Bay estuary, Florida, in the vicinity of a wastewater treatment plant (WWTP) outfall and a nearby reference site. Substrates were deployed floating at the surface and near the benthos in 5.4 m of water. Three sampling events covered a 1-month period coincident with declining seasonal WWTP flow and increasing dissolved oxygen (DO) levels in the bottom waters. Biomass accumulation in benthic biofilms appeared to be controlled by oxygen rather than nutrients. The overriding effect of DO was also seen in DNA fingerprints of community structure by terminal restriction fragment length polymorphism (T-RFLP) of amplified 16S rRNA genes. Ribotype diversity in benthic biofilms at both sites dramatically increased during the transition from hypoxic to normoxic. Terminal restriction fragment length polymorphism patterns showed pronounced differences between benthic and surface biofilm communities from the same site in terms of signal type, strength, and diversity, but minor differences between sites. Sequencing of 16S rRNA gene clone libraries from benthic biofilms at the WWTP site suggested that low DO levels favored sulfate-reducing prokaryotes (SRP), which decreased with rising oxygen levels and increasing overall diversity. A 91-bp ribotype in the CfoI-restricted 16S rRNA gene T-RFLP profiles, indicative of SRP, tracked the decrease in relative SRP abundance over time. PMID- 17351812 TI - Quantification of sulfate-reducing bacteria in industrial wastewater, by real time polymerase chain reaction (PCR) using dsrA and apsA genes. AB - Real-time polymerase chain reaction (PCR) is considered a highly sensitive method for the quantification of microbial organisms in environmental samples. This study was conducted to evaluate real-time PCR with SybrGreen detection as a quantification method for sulfate-reducing bacteria (SRB) in industrial wastewater produced by several chemical industries. We designed four sets of primers and developed standard curves based on genomic DNA of Desulfovibrio vulgaris from pure culture and on plasmids containing dissimilatory sulfate reductase (dsrA) or adenosine-5'-phosphosulfate reductase (apsA) genes of SRB. All the standard curves, two for dsrA and two for apsA genes, had a linear range between 0.95 x 10(2) and 9.5 x 10(6) copies/microL and between 1.2 x 10(3) and 1.2 x 10(7) copies/microL, respectively. The theoretical copy numbers of the tenfold dilutions of D. vulgaris genomic DNA were best estimated (between 2.7 to 10.5 times higher than theoretical numbers) by the standard curve with DSR1F and RH3-dsr-R primers. To mimic the effect of foreign DNA in environmental samples, serial dilutions of D. vulgaris genomic DNA were mixed with Escherichia coli chromosomal DNA (40 ng per assay). This influenced neither PCR amplification nor the quantification of target DNA. Industrial wastewater was sampled during a 15 month period and analyzed for the presence of SRB, based on dsrA gene amplification. SRB displayed a higher abundance during the summer (about 10(7) 10(8) targets mL(-1)) and lower during the winter (about 10(4)-10(5) targets mL( 1)). The results indicate that our real-time PCR approach can be used for detection of uncultured SRB and will provide valuable information related to the abundance of SRB in durable environmental samples, such as complex and saline industrial wastewaters. PMID- 17351814 TI - Arsenic occurrence in Brazil and human exposure. AB - Environmental exposure to arsenic (As) in terms of public health is receiving increasing attention worldwide following cases of mass contamination in different parts of the world. However, there is a scarcity of data available on As geochemistry in Brazilian territory, despite the known occurrence of As in some of the more severely polluted areas of Brazil. The purpose of this paper is to discuss existing data on As distribution in Brazil based on recent investigations in three contaminated areas as well as results from the literature. To date, integrated studies on environmental and anthropogenic sources of As contamination have been carried out only in three areas in Brazil: (1) the Southeastern region, known as the Iron Quadrangle, where As was released into the drainage systems, soils and atmosphere as a result of gold mining; (2) the Ribeira Valley, where As occurs in Pb-Zn mine wastes and naturally in As-rich rocks and soils; (3) the Amazon region, including the Santana area, where As is associated with manganese ores mined over the last 50 years. Toxicological studies revealed that the populations were not exposed to elevated levels of As, with the As concentrations in surface water in these areas rarely exceeding 10 microg/L. Deep weathering of bedrocks along with formation of Fe/Al-enriched soils and sediments function as a chemical barrier that prevents the release of As into the water. In addition, the tropical climate results in high rates of precipitation in the northern and southeastern regions and, hence, the As contents of drinking water is diluted. Severe cases of human As exposure related to non-point pollution sources have not been reported in Brazil. However, increasing awareness of the adverse health effects of As will eventually lead to a more complete picture of the distribution of As in Brazil. PMID- 17351813 TI - Bacteria of the Roseobacter clade show potential for secondary metabolite production. AB - Members of the Roseobacter clade are abundant and widespread in marine habitats and have very diverse metabolisms. Production of acylated homoserine lactones (AHL) and secondary metabolites, e.g., antibiotics has been described sporadically. This prompted us to screen 22 strains of this group for production of signaling molecules, antagonistic activity against bacteria of different phylogenetic groups, and the presence of genes encoding for nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS), representing enzymes involved in the synthesis of various pharmaceutically important natural products. The screening approach for NRPS and PKS genes was based on polymerase chain reaction (PCR) with degenerate primers specific for conserved sequence motifs. Additionally, sequences from whole genome sequencing projects of organisms of the Roseobacter clade were considered. Obtained PCR products were cloned, sequenced, and compared with genes of known function. With the PCR approach genes showing similarity to known NRPS and PKS genes were found in seven and five strains, respectively, and three PKS and NRPS sequences from genome sequencing projects were obtained. Three strains exhibited antagonistic activity and also showed production of AHL. Overall production of AHL was found in 10 isolates. Phylogenetic analysis of the 16S rRNA gene sequences of the tested organisms showed that several of the AHL-positive strains clustered together. Three strains were positive for three or four categories tested, and were found to be closely related within the genus Phaeobacter. The presence of a highly similar hybrid PKS/NRPS gene locus of unknown function in sequenced genomes of the Roseobacter clade plus the significant similarity of gene fragments from the strains studied to these genes argues for the functional requirement of the encoded hybrid PKS/NRPS complex. Our screening results therefore suggest that the Roseobacter clade is indeed employing PKS/NRPS biochemistry and should thus be further studied as a potential and largely untapped source of secondary metabolites. PMID- 17351815 TI - Distribution and phytoavailability of antimony at an antimony mining and smelting area, Hunan, China. AB - An investigation of the distribution, fractionation and phytoavailability of antimony (Sb) and other heavy metals in soil sampled at various locations in the vicinity of a Sb mine revealed elevated levels of Sb, most certainly due to the mining activities. The concentration of Sb in the soil samples was 100.6-5045 mg kg(-1); in comparison, the maximum permissible concentration for Sb in soil in The Netherlands is 3.5 mg kg(-1), and the maximum permissible concentration of pollutant Sb in receiving soils recommended by the World Health Organization is 36 mg kg(-1). The soil sampled near the Sb mine areas had also contained high concentrations of As and Hg. Root and leaf samples from plants growing in the Sb mine area contained high concentrations of Sb, with the concentration of Sb in the leaves of radish positively correlating with Sb concentrations in soil. The distribution of Sb in the soil showed the following order: strongly bound to the crystalline matrix > adsorbed on Fe/Mn hydrous oxides, complexed to organic/sulfides, bound to carbonates > weakly bound and soluble. Solvents showed varying levels of effectiveness in extracting Sb (based on concentration) from the soil, with SbNH4NO3 > SbEDTA > SbHAc, SbH2O > SbNH4OAc, in decreasing order. The concentration of easily phytoavailable Sb was high and varied from 2.5 to 13.2 mg kg(-1), the percentage of moderately phytoavailable Sb ranged from 1.62 to 8.26%, and the not phytoavailable fraction represented 88.2-97.9% of total Sb in soils. PMID- 17351816 TI - Multiple sex chromosome system of X1X1X2X2/X1X2)Y type in lutjanid fish, Lutjanus quinquelineatus (Perciformes). AB - The karyotype and other chromosomal markers as revealed by C-banding and Ag staining were studied in Lutjanus quinquelineatus and L. kasmira (Lutjanidae, Perciformes). While in latter species, the karyotype was invariably composed of 48 acrocentric chromosomes in both sexes, in L. quinquelineatus the female karyotype had exclusively 48 acrocentric chromosomes (2n = 48) but that of the male consisted of one large metacentric and 46 acrocentric chromosomes (2n = 47). The chromosomes in the first meiotic division in males showed 22 bivalents and one trivalent, which was formed by an end-to-end association and a chiasmatic association. Multiple sex chromosome system of X(1)X(1)X(2)X(2)/X(1)X(2)Y type resulting from single Robertsonian fusion between the original Y chromosome and an autosome was hypothesized to produce neo-Y sex chromosome. The multiple sex chromosome system of L. quinquelineatus appears to be at the early stage of the differentiation. The positive C-banded heterochromatin was situated exclusively in centromeric regions of all chromosomes in both species. Similarly, nucleolus organizer region sites were identified in the pericentromeric region of one middle-sized pair of chromosomes in both species. The cellular DNA contents were the same (3.3 pg) between the sexes and among this species and related species. PMID- 17351817 TI - The use of a non-LTR element to date the formation of the Sdic gene cluster. AB - Transposable elements comprise a considerable part of eukaryotic genomes, and there is increasing evidence for their role in the evolution of genomes. The number of active transposable elements present in the host genome at any given time is probably small relative to the number of elements that no longer transpose. The elements that have lost the ability to transpose tend to evolve neutrally. For example, non-LTR retrotransposons often become 5' truncated due to their own transposition mechanism and hence lose their ability to transpose. The resulting transposons can be characterized as "dead-on-arrival" (DOA) elements. Because they are abundant and ubiquitous, and evolve neutrally in the location where they were inserted, these DOA non-LTR elements make a useful tool to date molecular events. There are four copies of a "dead-on-arrival" RT1C element on the recently formed Sdic gene cluster of Drosophila melanogaster, that are not present in the equivalent region of the other species of the melanogaster subgroup. The life history of the RT1C elements in the genome of D. melanogaster was used to determine the insertion chronology of the elements in the cluster and to date the duplication events that originated this cluster. PMID- 17351818 TI - Quantitative covariance NMR by regularization. AB - The square root of a covariance spectrum, which offers high spectral resolution along both dimensions requiring only few t (1) increments, yields in good approximation the idealized 2D FT spectrum provided that the amount of magnetization exchanged between spins is relatively small. When this condition is violated, 2D FT and covariance peak volumes may differ. A regularization method is presented that produces a modified covariance spectrum with cross-peak volumes that closely match their 2D FT analogues. The method is demonstrated for TOCSY spectra with variable mixing times. PMID- 17351819 TI - Molecular cloning and expression characteristics of alternative oxidase gene of cotton (Gossypium hirsutum). AB - A novel alternative oxidase (AOX) gene derived from cotton (Gossypium hirsutum), designated as GhAOX1, was cloned with RACE-PCR. The full-length cDNA of GhAOX1was 1,298 bp in size, containing a 996 bp open reading frame (ORF) which corresponds to a precursor protein of 332 amino acid residues with a calculated molecular mass of 37.5 kDa. The predicted amino acid sequence exhibited 68.4%, 68.1%, 59.4%, and 69.8% homology to the alternative oxidases of Arabidopsis thaliana, Nicotiana tabacum, Solanum tuberosum and Glycine max, respectively. Interestingly, striking similarity in several coding regions, such as metal binding and hydrophobic alpha-helix regions was seen between GhAOX1 and other AOX1 proteins. Analysis of the exon/intron structure of the GhAOX1 gene showed that GhAOX1 consisted of four exons and three introns. Southern analysis indicated that the GhAOX1 was a single copy gene belonging to a multi-gene family. Expression analysis by Northern blot revealed that the GhAOX1 exhibited preferential expression in tissues, with the higher expression being found in cotyledons and petals. GhAOX1 was also found to be induced by a variety of stresses stimulation including cold, citrate, SA, KCN and antimycin A in cotton. PMID- 17351820 TI - Knocking down Wnt9a mRNA levels increases cellular proliferation. AB - Wnts are secreted lipid-modified signaling proteins. Activation of Wnt signalling in many tissues has also been associated with cancer. In many eukaryotes, expression of nuclear-encoded mRNA can be strongly inhibited by the presence of a small double-stranded RNA corresponding to exon sequences in the mRNA. In this study we used pAVU6+27 vectors, which have SalI and XbaI clone sites, to construct the siRNA expression vectors for human Wnt9a. Two kinds of small interfering RNA inserts were designed, synthesized and visually tested for efficacy by in situ hybridization, the results demonstrated that in the cells, transfected with U6+27 cassettes with anti-Wnt9a hairpin siRNA inserts, dramatically reduced Wnt9a signals were observed as compared to the untransfected cells. The results of flow cytometry analysis showed that the cell proliferation was promoted after lowering expression of the human Wnt9a in MCF-7 cells by RNAi, but was inhibited after over-expression of human Wnt9a. These results suggests the expression level of human Wnt9a in MCF-7 that breast cancer may play a role in adjusting the rate of cellular proliferation. PMID- 17351821 TI - Unlicensed and off-label use of medicines at a neonatology clinic in Italy. AB - OBJECTIVE: Many drugs used for children are not licensed or are used off-label. An increased risk of medication errors and unexpected adverse drug reactions (ADR) associated with off-label and unlicensed drug prescription has been reported. This risk increases in the newborn, who are more likely to be predisposed to an ADR due to their physiological immaturity. The objective of this study was to describe the use of unlicensed or off-label drugs in a Neonatal Intensive Care Unit (NICU). METHODS: All drugs prescribed to newborn admitted to the Neonatology Unit of Bari University Hospital, from July 1st to August 31st in 2004 were recorded. MAIN OUTCOME MEASURES: All the drugs prescribed were analysed with regard to their license status, then the licensed drugs were compared to the indications, dose, route of administration, duration of treatment, contraindications and warnings specified in the summary of product characteristics of the marketing authorization. RESULTS: Data were collected on 176 prescriptions for 61 different drugs given to 34 newborns. Drugs were licensed in 88% and unlicensed in 12% of cases. About the licensed drugs, in 37.5% medicines were used following the terms of the marketing authorization, in 22.7% of cases medicines were used in an off-label manner as they contained no information for paediatric use in the marketing authorization and in 27.8% of cases medicines were licensed for paediatric use, but they were used off-label with regard to age, dose, route of administration and duration of treatment. CONCLUSIONS: Despite European and American initiatives aiming to promote greater awareness and research in the paediatric population, these data demonstrate that there is still a high percentage of unlicensed or off-label drugs use in neonatology, underlining the need to stimulate scientific data collection by means of experimental studies or outcome research. PMID- 17351822 TI - Parent-proxy and child self-reported health-related quality of life: using qualitative methods to explain the discordance. AB - BACKGROUND: Although parent-proxy reports of health-related quality of life (HRQOL) are only moderately correlated with child reported HRQOL, it remains unknown why these scores differ. The aim of this study was to use a qualitative methodology to examine why parents and children report different levels of HRQOL. METHOD: The sample consisted of 15 parent-child pairs. A think-aloud technique was used where parents and children were given a generic HRQOL instrument (KIDSCREEN) and instructed to share their thoughts with the interviewer. Qualitative analyses were conducted to assess whether parents and children base their answer on different experiences or reasoning, have different response styles, or interpret the items differently. RESULTS: There was discordance between parents and children, in terms of rating scale and in terms of the reasoning for their answer. Children tended to have different response styles to parents, where for example, children tended to provide extreme scores (highest or lowest score) and base their response on one single example, more than parents. Parents and children interpreted the meaning of the items very similarly. DISCUSSION: This study provides evidence to suggest that discordance among parent child pairs on KIDSCREEN scores may be as a result of different reasoning and different response styles, rather than interpretation of items. These findings have important implications when parent-proxy reported HRQOL is used to guide clinical/treatment decisions. PMID- 17351823 TI - The mathematical relationship among different forms of responsiveness coefficients. AB - BACKGROUND: Little consensus exists regarding the most appropriate measure of responsiveness. While most indices are variants on Cohen's effect size, the mathematical relationships among these indices have not been elucidated. Consequently, the health-related quality of life (HRQL) literature contains many publications in which a variety of different indices are computed and differences among them noted. These differences are completely predictable when the underlying analytical form of each coefficient is explicated. METHODS: In this paper, we begin with a mathematical analysis of the variance components underlying an observed change score. From this, we determine analytically the relationships among the more commonly used indices of responsiveness. CONCLUSIONS: Based on this analysis, we conclude that Cohen's effect size and the Standardized Response Mean are the two most appropriate measures, as each provides unique information and each best captures an important relation between treatment effect and variability in response. However, the latter should be interpreted with caution, as under some circumstances, any measure based on variability in change scores can give misleading information. On this basis, we recommend that future analysis of responsiveness be restricted to the Cohen effect size to ensure interpretability and comparability with treatment effects in other domains. PMID- 17351824 TI - IRT health outcomes data analysis project: an overview and summary. AB - BACKGROUND: In June 2004, the National Cancer Institute and the Drug Information Association co-sponsored the conference, "Improving the Measurement of Health Outcomes through the Applications of Item Response Theory (IRT) Modeling: Exploration of Item Banks and Computer-Adaptive Assessment." A component of the conference was presentation of a psychometric and content analysis of a secondary dataset. OBJECTIVES: A thorough psychometric and content analysis was conducted of two primary domains within a cancer health-related quality of life (HRQOL) dataset. RESEARCH DESIGN: HRQOL scales were evaluated using factor analysis for categorical data, IRT modeling, and differential item functioning analyses. In addition, computerized adaptive administration of HRQOL item banks was simulated, and various IRT models were applied and compared. SUBJECTS: The original data were collected as part of the NCI-funded Quality of Life Evaluation in Oncology (Q-Score) Project. A total of 1,714 patients with cancer or HIV/AIDS were recruited from 5 clinical sites. MEASURES: Items from 4 HRQOL instruments were evaluated: Cancer Rehabilitation Evaluation System-Short Form, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Functional Assessment of Cancer Therapy and Medical Outcomes Study Short-Form Health Survey. RESULTS AND CONCLUSIONS: Four lessons learned from the project are discussed: the importance of good developmental item banks, the ambiguity of model fit results, the limits of our knowledge regarding the practical implications of model misfit, and the importance in the measurement of HRQOL of construct definition. With respect to these lessons, areas for future research are suggested. The feasibility of developing item banks for broad definitions of health is discussed. PMID- 17351825 TI - Next steps for use of item response theory in the assessment of health outcomes. AB - OBJECTIVES: We review the NCI/DIA conference, "Improving health outcomes assessment based on modern measurement theory and computerized adaptive testing," and suggest next steps in use of item response theory (IRT) to assess health outcomes. BACKGROUND: In recent years the level of interest and use of IRT methods has increased dramatically among health outcomes researchers. The NCI/DIA conference on June 24-25, 2004, was one of the first systematic opportunities to examine many challenging issues in applying IRT to the health outcomes field. METHOD: Based on the conference presentations, we identified five issues important to future applications of IRT to health outcomes. RESULTS: The five key issues are as follows: (1) collaboration between academia, government and industry; (2) common versus unique item banks; (3) educating and establishing standards for use and reporting of IRT; (4) demonstrating the value of IRT; and (5) continuing efforts to improve the user friendliness of IRT software. CONCLUSIONS: Moving forward will require a collaborative effort between academia, government agencies, and industry to design and conduct IRT research. A common item bank developed with collaboration from investigators from multiple institutions could be very valuable to the field. The establishment of consensus standards for use and reporting of IRT results would help users and consumers of the methodology. Clear documentation of how IRT can lead to better patient reported outcome measures and more accurate understanding of substantive issues is essential. Academia, government and industry should continue current work to enhance the user-friendliness of the IRT software. PMID- 17351826 TI - A practical approach to maternal phenylketonuria management. AB - More women with phenylketonuria are becoming pregnant and need appropriate management to avoid the effects of raised phenylalanine on the fetus: facial dysmorphism, microcephaly, growth retardation, developmental delay and congenital heart disease. Here we describe our experiences from a single centre gained over almost three decades. A series of six cases is presented to illustrate key points in management. Ideally, phenylalanine-restricted diet is started before conception in a planned fashion, but some women present pregnant and blood phenylalanine must be lowered rapidly. The aims of management are to maintain blood phenylalanine concentration in the target range (100-250 micromol/L) before and throughout the pregnancy, and to ensure adequate maternal nutrition and appropriate weight gain. Blood phenylalanine is monitored twice, three times a week, before and after conception respectively. Weight is monitored on a weekly basis and key micronutrients are monitored every 6-8 weeks in clinic. From the second trimester onwards, dietary phenylalanine intake has to be promptly increased, as phenylalanine tolerance increases rapidly. Postnatal management includes a neurological assessment of the infant at 4-8 weeks and an echocardiogram for infants conceived off diet. Subsequently, offspring are seen at 1 year, 4 years, 8 years and 14 years for neuropsychometric evaluations. Regular follow-up of the mother remains important whether on or off a phenylalanine-restricted diet. PMID- 17351827 TI - Localization and activity of calmodulin is involved in cell-cell adhesion of tumor cells and endothelial cells in response to hypoxic stress. AB - Adhesion of tumor cells to endothelial cells is known to be involved in the hematogenous metastasis of cancer, which is regulated by hypoxia. Hypoxia is able to induce a significant increase in free intracellular Ca2+ levels in both tumor cells and endothelial cells. Here, we investigate the regulatory effects of calmodulin (CaM), an intracellular calcium mediator, on tumor cell-endothelial cell adhesion under hypoxic conditions. Hypoxia facilitates HeLa cell-ECV304 endothelial cell adhesion, and results in actin cytoskeleton rearrangement in both endothelial cells and tumor cells. Suppression of CaM activation by CaM inhibitor W-7 disrupts actin cytoskeleton organization and CaM distribution in the cell-cell contact region, and thus inhibits cell-cell adhesion. CaM inhibitor also downregulates hypoxia-induced HIF-1-dependent gene expression. These results suggest that the Ca2+ -CaM signaling pathway might be involved in tumor cell endothelial cell adhesion, and that co-localization of CaM and actin at cell-cell contact regions might be essential for this process under hypoxic stress. PMID- 17351828 TI - Mutations in the TORNADO2 gene affect cellular decisions in the peripheral zone of the shoot apical meristem of Arabidopsis thaliana. AB - An EMS (ethyl methanesulfonate) mutagenesis effector screen performed with the STM:GUS marker line in Arabidopsis thaliana identified a loss-of-function allele of the TORNADO2 gene. The histological and genetic analyses described here implicate TRN2 in SAM function, where the peripheral zone in trn2 mutants is enlarged relative to the central stem cell zone. The trn2 mutant allele partially rescues the phenotype of shoot meristemless mutants but behaves additively to wuschel and clavata3 alleles during the vegetative phase and in the outer floral whorls. The development of carpels in trn2 wus-1 double mutant flowers indicates that pluripotent cells persist in floral meristems in the absence of TRN2 function and can be recruited for carpel anlagen. The data implicate a membrane bound plant tetraspanin protein in cellular decisions in the peripheral zone of the SAM. PMID- 17351829 TI - On rats, refuse, and recycling. PMID- 17351830 TI - In the heat of the summer : lessons from the heat waves in Paris. PMID- 17351831 TI - The genetic structure of populations of the vulnerable aquatic macrophyte Ranunculus nipponicus (Ranunculaceae). AB - Ranunculus nipponicus (Makino) Nakai is a vulnerable aquatic macrophyte in the Kinki district, which is the southernmost distribution of this species in Japan. The genetic diversity and structure within and among eleven extant populations were assessed using the inter-simple sequence repeats (ISSR) polymerase chain reaction in association with combinations of propagation pattern (clonal and/or seeds) and genotypic geographical structure. In total, 53 bands were amplified, of which 18 (34%) were polymorphic. Analysis of the ISSR bands identified 46 genotypes among 81 individuals from one stream population and 72 distinct genotypes among 147 individuals in the Kinki district. An unweighted pair group method with arithmetic mean (UPGMA) dendrogram showed some unity among upstream and downstream subpopulations within one stream and eleven populations. The Shannon index of genetic diversity was 0.109 for one stream population and 0.313 for total genetic diversity, suggesting relatively high genetic diversity. Analysis of molecular variance (AMOVA) revealed that 84.1% of the total genetic diversity occurred among populations and the remaining diversity (15.9%) occurred within populations. Significant genetic differentiation occurred among populations in the Kinki district. These results suggest that conservation of each population is important for maintaining genetic diversity of R. nipponicus in this district. PMID- 17351832 TI - Evaluation of recombinant HP6-Tsag, an 18 kDa Taenia saginata oncospheral adhesion protein, for the diagnosis of cysticercosis. AB - With the objective of providing inexpensive and reproducible assays for the detection of antibodies indicating exposure to Taenia saginata and Taenia solium, we have evaluated the diagnostic utility of the T. saginata oncosphere adhesion protein (HP6-Tsag), expressed in baculovirus (HP6-Bac) and bacteria (HP6-GST [glutathione S-transferase]), employing enzyme-linked immunosorbent assays (ELISAs) and sera from T. saginata infected cattle, T. solium infected pigs and serum and cerebrospinal fluid (CSF) samples from clinically defined T. solium neurocysticercosis (NCC) patients. The two recombinant proteins were antigenic in all three systems, with the signal to background ratio of the HP6-Bac ELISA slightly higher than that for the HP6-GST ELISA. Assay performance in cattle was similar to previously described peptide-based ELISA assays, although NCC sample sensitivity/specificity was marginally better. The sensitivity of the HP6-Bac and HP6-GST ELISAs was close for active human NCC (77.4 and 80.6% for serum and 76.9 and 73.1% for CSF samples, respectively). In inactive human NCC, however, the sensitivity of the HP6-Bac ELISA was almost twice that of the HP6-GST ELISA. Because peptides are relatively expensive and recombinant proteins are simple and economical to produce, the latter may provide useful reagents for antibody detection in countries with endemic cysticercosis/NCC. PMID- 17351833 TI - Improvement of a beta-glucanase activity test by taking into account the batch reactor balance of the test system. AB - Activity tests of enzymes are often applied for determining their concentration. In the easiest case, just one product concentration is measured after a given time. This often leads to nonlinear dependences of the apparent activity with enzyme protein concentration. A general solution of this problem consists in using the balance equation of the assay system, which commonly represents a batch reactor. Here, the balance equation of the batch for a general Michaelis Menten type reaction kinetics is used as the calibration function. The correlation of the apparent activity and enzyme concentration was established by capturing the enzyme by means of metal chelate interaction owing to a hexahistidine tag attached to the beta-glucanase. PMID- 17351834 TI - Measuring safety culture in the ambulatory setting: the safety attitudes questionnaire--ambulatory version. AB - BACKGROUND: Provider attitudes about issues pertinent to patient safety may be related to errors and adverse events. We know of no instruments that measure safety-related attitudes in the outpatient setting. OBJECTIVE: To adapt the safety attitudes questionnaire (SAQ) to the outpatient setting and compare attitudes among different types of providers in the outpatient setting. METHODS: We modified the SAQ to create a 62-item SAQ-ambulatory version (SAQ-A). Patient care staff in a multispecialty, academic practice rated their agreement with the items using a 5-point Likert scale. Cronbach's alpha was calculated to determine reliability of scale scores. Differences in SAQ-A scores between providers were assessed using ANOVA. RESULTS: Of the 409 staff, 282 (69%) returned surveys. One hundred ninety (46%) surveys were included in the analyses. Cronbach's alpha ranged from 0.68 to 0.86 for the scales: teamwork climate, safety climate, perceptions of management, job satisfaction, working conditions, and stress recognition. Physicians had the least favorable attitudes about perceptions of management while managers had the most favorable attitudes (mean scores: 50.4 +/- 22.5 vs 72.5 +/- 19.6, P < 0.05; percent with positive attitudes 18% vs 70%, respectively). Nurses had the most positive stress recognition scores (mean score 66.0 +/- 24.0). All providers had similar attitudes toward teamwork climate, safety climate, job satisfaction, and working conditions. CONCLUSION: The SAQ-A is a reliable tool for eliciting provider attitudes about the ambulatory work setting. Attitudes relevant to medical error may differ among provider types and reflect behavior and clinic operations that could be improved. PMID- 17351835 TI - Physician-patient communication about prescription medication nonadherence: a 50 state study of America's seniors. AB - CONTEXT: Understanding and improving the quality of medication management is particularly important in the context of the Medicare prescription drug benefit that took effect last January 2006. OBJECTIVE: To determine the prevalence of physician-patient dialogue about medication cost and medication adherence among elderly adults nationwide. DESIGN: Cross-sectional survey. PARTICIPANTS: National stratified random sample of community-dwelling Medicare beneficiaries aged 65 and older. MAIN OUTCOME MEASURES: Rates of physician-patient dialogue about nonadherence and cost-related medication switching. RESULTS: Forty-one percent of seniors reported taking five or more prescription medications, and more than half has 2 or more prescribing physicians. Thirty-two percent overall and 24% of those with 3 or more chronic conditions reported not having talked with their doctor about all their different medicines in the last 12 months. Of seniors reporting skipping doses or stopping a medication because of side effects or perceived nonefficacy, 27% had not talked with a physician about it. Of those reporting cost-related nonadherence, 39% had not talked with a physician about it. Thirty eight percent of those with cost-related nonadherence reported switching to a lower priced drug, and in a multivariable model, having had a discussion about drug cost was significantly associated with this switch (odds ratio [OR] 5.04, 95% confidence interval [CI] 4.28-5.93, P < .001). CONCLUSIONS: We show that there is a communication gap between seniors and their physicians around prescription medications. This communication problem is an important quality and safety issue, and takes on added salience as physicians and patients confront new challenges associated with coverage under new Medicare prescription drug plans. Meeting these challenges will require that more attention be devoted to medication management during all clinical encounters. PMID- 17351836 TI - Relationship between peer assessment during medical school, dean's letter rankings, and ratings by internship directors. AB - BACKGROUND: It is not known to what extent the dean's letter (medical student performance evaluation [MSPE]) reflects peer-assessed work habits (WH) skills and/or interpersonal attributes (IA) of students. OBJECTIVE: To compare peer ratings of WH and IA of second- and third-year medical students with later MSPE rankings and ratings by internship program directors. DESIGN AND PARTICIPANTS: Participants were 281 medical students from the classes of 2004, 2005, and 2006 at a private medical school in the northeastern United States, who had participated in peer assessment exercises in the second and third years of medical school. For students from the class of 2004, we also compared peer assessment data against later evaluations obtained from internship program directors. RESULTS: Peer-assessed WH were predictive of later MSPE groups in both the second (F = 44.90, P < .001) and third years (F = 29.54, P < .001) of medical school. Interpersonal attributes were not related to MSPE rankings in either year. MSPE rankings for a majority of students were predictable from peer assessed WH scores. Internship directors' ratings were significantly related to second- and third-year peer-assessed WH scores (r = .32 [P = .15] and r = .43 [P = .004]), respectively, but not to peer-assessed IA. CONCLUSIONS: Peer assessment of WH, as early as the second year of medical school, can predict later MSPE rankings and internship performance. Although peer-assessed IA can be measured reliably, they are unrelated to either outcome. PMID- 17351837 TI - HIV-infected African Americans are willing to participate in HIV treatment trials. AB - BACKGROUND: Despite the high prevalence rates of HIV infection in the African American community, African Americans remain underrepresented in HIV treatment trials. OBJECTIVE: (1) To develop a questionnaire that measures attitudes and concerns about HIV treatment trials among HIV-infected African Americans at a university-based clinic. (2) To determine actual participation rates and willingness to participate in future HIV treatment trials among HIV-infected African Americans at a university-based clinic. DESIGN: Questionnaire development and cross-sectional survey. SETTING, PARTICIPANTS, AND MEASUREMENTS: In a sample of 200 HIV-infected African-American adults receiving medical care at the Pittsburgh AIDS Center for Treatment (a university-based ambulatory clinic), we assessed research participation rates and willingness to participate in future HIV treatment trials, trust in the medical profession, sociodemographic characteristics, attitudes, and concerns about HIV treatment trials. MAIN OUTCOME MEASURES: Research participation rates and willingness to participate in future HIV treatment trials. RESULTS: Only 57% of survey respondents had ever been asked to participate in an HIV treatment trial but 86% of those asked said yes. Prior research participation was significantly related to willingness to participate in future HIV treatment trials (P = .001). Contrary to previous studies, neither trust/distrust in the medical profession nor beliefs about the dishonesty of researchers was associated with research participation rates or willingness to participate in future HIV treatment trials. CONCLUSIONS: Having never been asked to participate in research is a major barrier to the participation of HIV infected African Americans in HIV treatment trials. African Americans who seek medical care for HIV infection should be asked to participate in HIV treatment trials. PMID- 17351838 TI - Computers in the exam room: differences in physician-patient interaction may be due to physician experience. AB - BACKGROUND: The use of electronic medical records can improve the technical quality of care, but requires a computer in the exam room. This could adversely affect interpersonal aspects of care, particularly when physicians are inexperienced users of exam room computers. OBJECTIVE: To determine whether physician experience modifies the impact of exam room computers on the physician patient interaction. DESIGN: Cross-sectional surveys of patients and physicians. SETTING AND PARTICIPANTS: One hundred fifty five adults seen for scheduled visits by 11 faculty internists and 12 internal medicine residents in a VA primary care clinic. MEASUREMENTS: Physician and patient assessment of the effect of the computer on the clinical encounter. MAIN RESULTS: Patients seeing residents, compared to those seeing faculty, were more likely to agree that the computer adversely affected the amount of time the physician spent talking to (34% vs 15%, P = 0.01), looking at (45% vs 24%, P = 0.02), and examining them (32% vs 13%, P = 0.009). Moreover, they were more likely to agree that the computer made the visit feel less personal (20% vs 5%, P = 0.017). Few patients thought the computer interfered with their relationship with their physicians (8% vs 8%). Residents were more likely than faculty to report these same adverse effects, but these differences were smaller and not statistically significant. CONCLUSION: Patients seen by residents more often agreed that exam room computers decreased the amount of interpersonal contact. More research is needed to elucidate key tasks and behaviors that facilitate doctor-patient communication in such a setting. PMID- 17351839 TI - Acting on reflection: the effect of reflection on students' clinical performance on a standardized patient examination. AB - BACKGROUND: Little evidence exists to support the value of reflection in the clinical setting. OBJECTIVE: To determine whether reflecting and revisiting the "patient" during a standardized patient (SP) examination improves junior medical students' performance and to analyze students' perceptions of its value. DESIGN: Students completed a six-encounter clinical skills examination, writing a guided assessment after each encounter to trigger reflection. SPs evaluated the students with Medical Skills and Patient Satisfaction checklists. During the last three encounters, students could opt to revisit the SP and be reevaluated with identical checklists. PARTICIPANTS: One hundred and forty-nine third year medical students. MEASUREMENTS: Changes in scores in the Medical Skills and Patient Satisfaction checklists between first visit and revisit were tested separately per case as well as across cases. RESULTS: On the medical skills and patient satisfaction checklists, mean revisit scores across cases were significantly higher than mean first visit scores [12.6 vs 12.2 (pooled SD = 2.4), P = .0001; 31.2 vs 31.0 (pooled SD = 3.5), P = .0001)]. Sixty-five percent of the time, students rated "reflect-revisit" positively, 34% neutrally, and 0.4% negatively. Five themes were identified in the positive comments: enhancement of (1) medical decision making, (2) patient education/counseling, (3) student satisfaction/confidence, (4) patient satisfaction/confidence, and (5) clinical realism. CONCLUSIONS: Offering third year medical students the option to reflect and revisit an SP during a clinical skills examination produced a small but nontrivial increase in clinical performance. Students perceived the reflect revisit experience as enhancing patient-centered practices (counseling, education) as well as their own medical decision making and clinical confidence. PMID- 17351840 TI - Gender differences in aspirin use among adults with coronary heart disease in the United States. AB - BACKGROUND: Aspirin reduces mortality for men and women with coronary heart disease (CHD). Previous research suggests women with acute coronary syndromes receive less aggressive care, including less frequent early administration of aspirin. The presence of gender differences in aspirin use for secondary prevention is less clear. OBJECTIVE: To determine if a gender difference exists in the use of aspirin for secondary prevention among individuals with CHD. DESIGN: We analyzed data from the nationally representative 2000-2002 Medical Expenditure Panel Surveys to determine the prevalence of regular aspirin use among men and women with CHD. PARTICIPANTS: Participants, 1,869, 40 years and older who reported CHD or prior myocardial infarction. RESULTS: Women were less likely than men to use aspirin regularly (62.4% vs 75.6%, p < .001) even after adjusting for demographic, socioeconomic and clinical characteristics (adjusted OR = 0.62, 95% CI, 0.48-0.79). This difference narrowed but remained significant when the analysis was limited to those without self-reported contraindications to aspirin (79.8% vs 86.4%, P = .002, adjusted OR = 0.68, 95% CI, 0.48-0.97). Women were more likely than men to report contraindications (20.5% vs 12.5%, P < .001). Differences in aspirin use were greater between women and men with private health insurance (61.8% vs 79.0%, P < .001, adjusted OR = 0.48, 95% CI, 0.35-0.67) than among those with public coverage (62.5% vs 70.7%, P = .04, adjusted OR = 0.74, 95% CI, 0.50-1.11) (P < .001 for gender-insurance interaction). CONCLUSION: We found a gender difference in aspirin use among patients with CHD not fully explained by differences in patient characteristics or reported contraindications. These findings suggest a need for improved secondary prevention of cardiovascular events for women with CHD. PMID- 17351841 TI - Impact of pneumococcal vaccination on pneumonia rates in patients with COPD and asthma. AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are included in several national pneumococcal vaccination recommendations whereas asthma patients are not. The objective of this study was to evaluate pneumonia related hospitalization risk in patients with COPD or asthma and vaccination impact. METHODS: We identified patients with documented pneumococcal vaccination from a cohort of veterans with either a diagnosis of asthma or COPD and their matched controls. Patients were identified between October 1, 1997 and September 30, 1998 and followed for 5 years. For each group we identified pneumococcal pneumonia hospitalizations and all pneumonia-related hospitalizations in the periods before and after vaccination. We estimated hospitalization rates and compared rates in the asthma and COPD groups to controls using negative binomial regression models. RESULTS: We identified 16,074 COPD patients (average age 65.8 years), 14,028 controls for the COPD patients (average age 67.5 years), 2,746 asthma patients (average age 53.0 years), and 1,345 controls for the asthma patients (average age 59.2 years). Compared to controls, the adjusted risk of pneumococcal pneumonia hospitalizations before pneumococcal vaccination was COPD = 8.02 (95% CI, 4.44-14.48) and asthma = 0.76 (0.17-3.53). For any pneumonia related hospitalization, the adjusted risk was COPD = 3.91 (3.40-4.50) and asthma = 1.45 (0.85-2.46). After vaccination, events decreased in all groups. The adjusted risk for pneumococcal pneumonia hospitalizations postvaccination was COPD = 3.87 (2.55-5.88) and asthma = 0.30 (0.04-1.99). For any pneumonia-related hospitalization the adjusted risk was COPD = 3.71 (3.33-4.13) and asthma = 0.79 (0.50-1.25). CONCLUSIONS: This study supports the value of vaccinating COPD patients; however, the value of vaccination for asthma patients is less certain. PMID- 17351842 TI - Average household exposure to newspaper coverage about the harmful effects of hormone therapy and population-based declines in hormone therapy use. AB - BACKGROUND: The news media facilitated the rapid dissemination of the findings from the estrogen plus progestin therapy arm of the Women's Health Initiative (EPT-WHI). OBJECTIVE: To examine the relationship between the potential exposure to newspaper coverage and subsequent hormone therapy (HT) use. DESIGN/POPULATION: Population-based cohort of women receiving mammography at 7 sites (327,144 postmenopausal women). MEASUREMENTS: The outcome was the monthly prevalence of self-reported HT use. Circulation data for local, regional, and national newspapers was used to create zip-code level measures of the estimated average household exposure to newspaper coverage that reported the harmful effects of HT in July 2002. RESULTS: Women had an average potential household exposure of 1.4 articles. There was substantial variation in the level of average household exposure to newspaper coverage; women from rural sites received less than women from urban sites. Use of HT declined for all average potential exposure groups after the publication of the EPT-WHI. HT prevalence among women who lived in areas where there was an average household exposure of at least 3 articles declined significantly more (45 to 27%) compared to women who lived in areas with <1 article (43 to 31%) during each of the subsequent 5 months (relative risks 0.86-0.92; p < .006 for all). CONCLUSIONS: Greater average household exposure to newspaper coverage about the harms associated with HT was associated with a large population-based decline in HT use. Further studies should examine whether media coverage directly influences the health behavior of individual women. PMID- 17351843 TI - An exploratory study of primary care physician decision making regarding total joint arthroplasty. AB - BACKGROUND: For patients to experience the benefits of total joint arthroplasty (TJA), primary care physicians (PCPs) ought to know when to refer a patient for TJA and/or optimize nonsurgical treatment options for osteoarthritis (OA). OBJECTIVE: To evaluate the ability of physicians to make clinical treatment decisions. DESIGN AND PARTICIPANTS: A survey, using ten clinical vignettes, of PCPs in Indiana. MEASUREMENTS: A test score (range 0 to 10) was computed based on the number of correct answers consistent with published explicit appropriateness criteria for TJA. We also collected demographic characteristics and physicians' perceived success rate of TJA in terms of pain relief and functional improvement. RESULTS: There were 149 PCPs (response rate = 61%) who participated. The mean test score was 6.5 +/- 1.5. Only 17% correctly identified the published success rate of TJA (i.e., > or =90%). In multivariate analysis, the only physician related variables associated with test score were ethnicity, board status, and perceived success rate of TJA. Physicians who were white (P = .001), board certified (P = .04), and perceived a higher success rate of TJA (P = .004) had higher test scores. CONCLUSIONS: PCP knowledge with respect to guideline concordant care for OA could be improved, specifically in deciding when to consider TJA versus optimizing nonsurgical options. Moreover, the perception of the success rate of TJA may influence a clinician's decision making. PMID- 17351844 TI - A national survey of medical students' beliefs and knowledge in screening for prostate cancer. AB - BACKGROUND: Today's medical students are being educated at a time when there are no evidence-based guidelines for prostate cancer screening. OBJECTIVE: To examine medical students' knowledge and beliefs concerning prostate cancer screening and specific determinants for their beliefs. DESIGN, SETTING, AND PARTICIPANTS: One thousand six hundred and forty four students were sampled at 20 medical schools using a web-based, cross-sectional survey. MAIN OUTCOME MEASURES: Basic knowledge and beliefs about prostate cancer testing, epidemiology, and therapy were ascertained. RESULTS: Four of 8 knowledge items were answered incorrectly by 50% or more of students. Seven of 8 students believe that early diagnosis from screening can improve survival from prostate cancer. Second- and third-year students were more likely than fourth-year students to believe that the digital rectal exam (DRE) and the prostate-specific antigen test were accurate, adjusted odds ratio (AOR) 1.8; 95% confidence interval (CI), 1.2 to 2.7 and 1.7; 1.3 to 2.2 for second and third years, respectively, for the DRE. Black and Hispanic students were no more likely than white students to agree that early screening diagnosis improves survival, but blacks were more likely to agree with screening black or Hispanic men (AOR 7.8; 95% CI, 5.3 to 11.4 and 3.2; 2.2 to 4.7, respectively). More knowledgeable students were less likely to believe in the benefit of early detection and the accuracy of the prostate-specific antigen (AOR 0.3; 95%CI, 0.2 to 0.5). CONCLUSIONS: Medical students generally are very optimistic about the benefits of screening for prostate cancer. Increased knowledge about prostate cancer is associated with a more conservative view of screening. Other predictors are independent of this knowledge. PMID- 17351845 TI - The effect of patients' met expectations on consultation outcomes. A study with family medicine residents. AB - OBJECTIVES: To know the patients' expectations and the fulfillment of these at family medicine consultations by resident doctors and to assess their effect on some consultation outcomes. DESIGN: A prospective cohort study. PARTICIPANTS: Patients attending family medicine consultations held by 38 resident doctors: 1,301 eligible patients, 702 filled in all questionnaires. MEASUREMENTS: Before each visit, the patients' expectations about that particular consultation were registered. Right after the visit was over, their perception of several aspects of the communicative interaction with the doctor was measured. Later, patients were interviewed on the phone to know how their expectations had been fulfilled, how satisfied they were about the consultation, how they had followed the doctor's suggestions, if they were going to seek further care for the same cause later, and the evolution of their clinical problem. Logistic regression was the main analysis used. RESULTS: The most common expectations were the doctor showing interest and listening (30.5%), getting some information about the diagnosis (16.3%), and sharing problems and doubts (11.1%). The rate of main expectations that were met was 76.5%. Satisfaction with the encounter was associated with the clinical evolution [odds ratio (OR) 2.23; confidence interval (CI): 1.32-3.75], and the fulfilling of the patients' main or two main expectations was significantly related to all the measured outcomes (satisfaction OR 3.51, CI: 1.73-7.8; adherence OR 1.80, CI: 1.11-2.92; clinical evolution OR 1.54, CI: 1.01 2.35; and seeking further care later OR 0.54, CI:0.36-0.81) CONCLUSIONS: Patients prioritize expectations of a more general sort when they attend primary care consultations and residents fulfill these acceptably. The fulfillment of expectations seems to affect the studied outcomes more than other factors. PMID- 17351847 TI - Patient receipt and understanding of written information provided with isotretinoin and estrogen prescriptions. AB - BACKGROUND: Medication guides (MG) and mandatory patient package inserts (MPPI) are required with some prescription medications. OBJECTIVE: We sought to determine how many patients receive, read, and understand these mandated materials. DESIGN AND PARTICIPANTS: A total of 3,620 patients were identified as filling prescriptions for isotretinoin or selected estrogen products from February 2004 to January 2005. Patients were surveyed to gauge receipt and understanding of the MG for isotretinoin and the MPPI for estrogen. MEASUREMENTS AND MAIN RESULTS: A total of 500 patients completed the survey, with 186 (93%) of the 200 isotretinoin patients and 258 (86%) of the 300 estrogen patients reporting receipt of the MG/MPPI with their most recent prescription. The majority of respondents reported confidence in their knowledge of their medication (86% for isotretinoin and 75% for estrogen). However, the mean score on 5 questions assessing recognition of medication risks was only slightly better than the score expected from guessing (3.1 vs 2.5, P < .01 for both isotretinoin and estrogen). CONCLUSIONS: Despite receiving the information and reporting confidence in medication knowledge, patients' understanding of major risks with these medications was poor. This finding highlights the need to develop better risk communication strategies to improve the safe and effective use of prescription medications. PMID- 17351846 TI - Alcohol consumption among older adults in primary care. AB - BACKGROUND: Alcohol misuse is a growing public health concern for older adults, particularly among primary care patients. OBJECTIVES: To determine alcohol consumption patterns and the characteristics associated with at-risk drinking in a large sample of elderly primary care patients. DESIGN: Cross-sectional analysis of multisite screening data from 6 VA Medical Centers, 2 hospital-based health care networks, and 3 Community Health Centers. PARTICIPANTS: Patients, 43,606, aged 65 to 103 years, with scheduled primary care appointments were approached for screening; 27,714 (63.6%) consented to be screened. The final sample of persons with completed screens comprised 24,863 patients. MEASUREMENTS: Quantity and frequency of alcohol use, demographics, social support measures, and measures of depression/anxiety. RESULTS: Of the 24,863 older adults screened, 70.0% reported no consumption of alcohol in the past year, 21.5% were moderate drinkers (1-7 drinks/week), 4.1% were at-risk drinkers (8-14 drinks/week), and 4.5% were heavy (>14 drinks/week) or binge drinkers. Heavy drinking showed significant positive association with depressive/anxiety symptoms [Odds ratio (OR) (95% CI): 1.79 (1.30, 2.45)] and less social support [OR (95% CI): 2.01 (1.14, 2.56)]. Heavy drinking combined with binging was similarly positively associated with depressive/anxiety symptoms [OR (95%): 1.70 (1.33, 2.17)] and perceived poor health [OR (95% CI): 1.27 (1.03, 1.57)], while at-risk drinking was not associated with any of these variables. CONCLUSIONS: The majority of participants were nondrinkers; among alcohol users, at-risk drinkers did not differ significantly from moderate drinkers in their characteristics or for the 3 health parameters evaluated. In contrast, heavy drinking was associated with depression and anxiety and less social support, and heavy drinking combined with binge drinking was associated with depressive/anxiety symptoms and perceived poor health. PMID- 17351848 TI - Internal medicine residents reject "longer and gentler" training. AB - BACKGROUND: Increasing complexity of medical care, coupled with limits on resident work hours, has prompted consideration of extending Internal Medicine training. It is unclear whether further hour reductions and extension of training beyond the current duration of 3 years would be accepted by trainees. OBJECTIVE: We aimed to determine if further work-hour reductions and extension of training would be accepted by trainees and whether resident burnout affects their opinions. DESIGN: A postal survey was sent to all 143 Internal Medicine residents at the University of Colorado School of Medicine in May 2004. MEASUREMENTS: The survey contained questions related to opinions on work-hour limits using a 5 point Likert scale ranging from strongly agree to strongly disagree. Burnout was measured using the Maslach Burnout Inventory, organized into three subscales: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment, with burnout defined as high EE or DP. RESULTS: Seventy-four percent (106/143) of residents returned the survey. The vast majority (84%) of residents disagreed or strongly disagreed with extending training to 4 or 5 years. Burnout residents were less averse to extending training (strongly agree or agree, 18.9% vs 4.3%, P = .04). The majority of residents (68.9%) disagreed or strongly disagreed with establishing a 60-hour/week limit. Residents who met the criteria for burnout were more likely to agree that a 60-hour limit would be better than an 80-hour limit (strongly agree or agree, 22% vs 8%, P = .02). CONCLUSIONS: In this program, most Internal Medicine residents are strongly opposed to extending their training to 4 or 5 years and would prefer the current 80 hours/week cap. A longer, less intense pace of Internal Medicine training seems to be less attractive in the eyes of current trainees. PMID- 17351849 TI - Air travel and venous thromboembolism: a systematic review. AB - CONTEXT: Despite multiple attempts to document and quantify the danger of venous thromboembolism (VTE) following prolonged travel, there is still uncertainty about the magnitude of risk and what can be done to lower it. OBJECTIVES: To review the methodologic strength of the literature, estimate the risk of travel related VTE, evaluate the efficacy of preventive treatments, and develop evidence based recommendations for practice. DATA SOURCES: Studies identified from MEDLINE from 1966 through December 2005, supplemented by a review of the Cochrane Central Registry of Controlled Trials, the Database of Abstracts of Reviews of Effects, and relevant bibliographies. STUDY SELECTION: We included all clinical studies that either reported primary data concerning travel as a risk factor for VTE or tested preventive measures for travel-related VTE. DATA EXTRACTION AND ANALYSIS: Two reviewers reviewed each study independently to assess inclusion criteria, classify research design, and rate methodologic features. The effect of methodologic differences, VTE risk, and travel duration on VTE rate was evaluated using a logistic regression model. DATA SYNTHESIS: Twenty-four published reports, totaling 25 studies, met inclusion criteria (6 case-control studies, 10 cohort studies, and 9 randomized controlled trials). Method of screening for VTE [screening ultrasound compared to usual clinical care, odds ratio (OR) 390], outcome measure [all VTE compared to pulmonary embolism (PE) only, OR 21], duration of travel (<6 hours compared to 6-8 hours, OR 0.011), and clinical risk ("higher" risk travelers compared to "lower," OR 3.6) were significantly related to VTE rate. Clinical VTE after prolonged travel is rare [27 PE per million flights diagnosed through usual clinical care, 0.05% symptomatic deep venous thrombosis (DVT) diagnosed through screening ultrasounds], but asymptomatic thrombi of uncertain clinical significance are more common. Graduated compression stockings prevented travel-related VTE (P < 0.05 in 4 of 6 studies), aspirin did not, and low-molecular-weight heparin (LMWH) showed a trend toward efficacy in one study. CONCLUSIONS: All travelers, regardless of VTE risk, should avoid dehydration and frequently exercise leg muscles. Travelers on a flight of less than 6 hours and those with no known risk factors for VTE, regardless of the duration of the flight, do not need DVT prophylaxis. Travelers with 1 or more risk factors for VTE should consider graduated compression stockings and/or LMWH for flights longer than 6 hours. PMID- 17351850 TI - Racial/ethnic differences in multiple self-care behaviors in adults with diabetes. AB - OBJECTIVE: To assess racial/ethnic differences in multiple diabetes self-care behaviors. DESIGN: Cross-sectional study. PARTICIPANTS: 21,459 participants with diabetes in the 2003 Behavioral Risk Factor Surveillance survey. MEASUREMENTS: The study assessed self-care behaviors including physical activity, fruits/vegetables consumption, glucose testing, and foot examination, as well as a composite of the 4 self-care behaviors across racial/ethnic groups. Multiple logistic regression was used to assess the independent association between race/ethnicity, the composite variable, and each self-care behavior controlling for covariates. STATA was used for statistical analysis. RESULTS: Overall, 6% engaged in all 4 self-care behaviors, with a range of 5% in non-insulin users to 8% in insulin users. Blacks were less likely to exercise (OR 0.63, 95% CI 0.51, 0.79), while Hispanics and "others" were not significantly different from whites. Hispanics (OR 0.64, 95% CI 0.49, 0.82) and others (OR 0.69, 95% CI 0.49, 0.96) were less likely to do home glucose testing, while blacks were not significantly different from whites. Blacks (OR 1.42, 95% CI 1.12, 1.80) were more likely to do home foot examinations, while Hispanics and others were not significantly different from whites. Blacks (OR 0.56, 95% CI 0.36, 0.87) were less likely to engage in all 4 behaviors, while Hispanics and others were not significantly different from whites. There were no significant racial/ethnic differences in fruit and vegetable consumption. CONCLUSIONS: Few patients engage in multiple self-care behaviors at recommended levels, and there are significant racial/ethnic differences in physical activity, dietary, and foot care behaviors among adults with diabetes. PMID- 17351851 TI - Early initiation of colorectal cancer screening in individuals with affected first-degree relatives. AB - BACKGROUND: Several guidelines recommend initiating colorectal cancer screening at age 40 for individuals with affected first-degree relatives, yet little evidence exists describing how often these individuals receive screening procedures. OBJECTIVES: To determine the proportion of individuals in whom early initiation of colorectal cancer screening might be indicated and whether screening disparities exist. DESIGN: Population-based Supplemental Cancer Control Module to the 2000 National Health Interview Survey. PARTICIPANTS: Respondents, 5,564, aged 40 to 49 years were included within the analysis. MEASUREMENTS: Patient self-report of sigmoidoscopy, colonoscopy, or fecal occult blood test. RESULTS: Overall, 279 respondents (5.4%: 95% C.I., 4.7, 6.2) reported having a first-degree relative affected with colorectal cancer. For individuals with a positive family history, 67 whites (27.9%: 95% C.I., 21.1, 34.5) and 3 African American (9.3%: 95% C.I., 1.7, 37.9) had undergone an endoscopic procedure within the previous 10 years (P-value = .03). After adjusting for age, family history, gender, educational level, insurance status, and usual source of care, whites were more likely to be current with early initiation endoscopic screening recommendations than African Americans (OR = 1.38: 95% C.I., 1.01, 1.87). Having an affected first-degree relative with colorectal cancer appeared to have a stronger impact on endoscopic screening for whites (OR = 3.21: 95% C.I., 2.31, 4.46) than for African Americans (OR = 1.05: 95% C.I., 0.15, 7.21). CONCLUSIONS: White participants with a family history are more likely to have endoscopic procedures beginning before age 50 than African Americans. PMID- 17351852 TI - Pharyngitis management: defining the controversy. AB - Despite numerous controlled trials, clinical practice guidelines and cost effective analyses, controversy persists regarding the appropriate management strategy for adult pharyngitis. In this perspective, we explore this controversy by comparing two competing clinical guidelines. Although the guidelines appear to make widely diverging recommendations, we show that the controversy centers on only a small proportion of patients: those presenting with severe pharyngitis. We examine recently published data to illustrate that this seemingly simple problem of strep throat remains a philosophical issue: should we give primacy to relieving acute time-limited symptoms, or should we emphasize the potential societal risk of antibiotic resistance? We accept potentially over treating a minority of adult pharyngitis patients with the most severe presentations to reduce suffering in an approximately equal number of patients who will have false negative test results if the test-and-treat strategy were used. PMID- 17351853 TI - The role of internists during epidemics, outbreaks, and bioterrorist attacks. AB - Internists are well-positioned to play significant roles in recognizing and responding to epidemics, outbreaks, and bioterrorist attacks. They see large numbers of patients with various health problems and may be the patients' only interaction with the medical community for symptoms resulting from infectious diseases and injuries from radiation, chemicals, and/or burns. Therefore, Internists must understand early warning signs of different bioterrorist and infectious agents, proper reporting channels and measures, various ways that they can assist the public health response, and roles of different local, state, and federal agencies. In addition, it is important to understand effects of a public health disaster on clinic operations and relevant legal consequences. PMID- 17351854 TI - Professionalism and evolving concepts of quality. AB - For much of the twentieth century, quality of care was defined specifically in terms of physician characteristics and behaviors. High-quality physicians were well trained, knowledgeable, skillful, and compassionate. More recently, quality of care has been defined in terms of systems of care. High-quality organizations develop and adopt practices to reduce adverse events and optimize outcomes. This essay discusses this transformation from physician-based to organization-based concepts of quality and the consequences for patient care and medical professionalism. PMID- 17351856 TI - Rhabdomyolysis and acute renal failure after fire ant bites. AB - We describe a 59-year-old patient who developed acute renal failure because of rhabdomyolysis after extensive red fire ant bites. This case illustrates a serious systemic reaction that may occur from fire ant bites. Consistent with the clinical presentation in rhabdomyolysis associated with non-traumatic causes, hyperkalemia, hypophosphatemia, hypocalcemia, and high anion gap acidosis were not observed in this patient. While local allergic reactions to fire ant bites are described in the literature, serious systemic complications with rhabdomyolysis and renal failure have not been previously reported. It is our effort to alert the medical community of the possibility of such a complication that can occur in the victims of fire ant bites. PMID- 17351855 TI - Giant cell arteritis presenting as small bowel infarction. AB - Giant cell arteritis predominantly affects cranial arteries and rarely involves other sites. We report a patient who presented with small bowel obstruction because of infarction from mesenteric giant cell arteritis. She had an unusual cause of her obstruction and a rare manifestation of giant cell arteritis. In spite of aggressive therapy with steroids, she died a month later because of multiple complications. We discuss the diagnosis and management of small bowel obstruction and differential diagnosis of vasculitis of the gastrointestinal tract. We were able to find 11 cases of bowel involvement with giant cell arteritis in the English literature. This case report illustrates that giant cell arteritis can be a cause of small bowel obstruction and bowel infarction. In the proper clinical setting, vasculitides need to be considered early in the differential diagnosis when therapy may be most effective. PMID- 17351857 TI - Reversible pulmonary hypertension and isolated right-sided heart failure associated with hyperthyroidism. AB - Hyperthyroidism may present with signs and symptoms related to dysfunction of a variety of organs. Cardiovascular pathology in hyperthyroidism is common. A few case reports describe isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension as the prominent cardiovascular manifestations of hyperthyroidism. Although most textbooks do not mention hyperthyroidism as a cause of pulmonary hypertension and isolated right heart failure, the literature suggests that some hyperthyroid patients may develop reversible pulmonary hypertension and isolated right heart failure. We report a case of hyperthyroidism presenting with signs and symptoms of isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension, which resolved with treatment of hyperthyroidism. PMID- 17351858 TI - Spinal cord infarction with multiple etiologic factors. AB - Spinal cord infarction is uncommon and usually presents with sudden onset of paralysis and sensory disturbances. A variety of causes are described, but rarely with multiple factors involved. We report a case of a 63-year-old man with a history of diabetes mellitus, hypertension, and osteoarthritis who presented with acute onset of chest pain, numbness, and weakness associated with episodic hypotension. He had incomplete tetraplegia and was areflexic without spasticity. Pain and temperature sensations were impaired below the C7 dermatome and absent below the T4 dermatome bilaterally. Proprioception and vibration sensations were diminished on the right below the C6 dermatome. Magnetic resonance imaging showed spinal cord infarction affecting C6-T3 segments, and severe cervical and lumbar spine degenerative changes. This case illustrates an unusual presenting symptom of spinal infarction, the need to identify multiple risk factors for spinal cord infarction, and the importance of optimal preventive therapy in patients at risk. PMID- 17351859 TI - Measuring a safety culture: critical pathway or academic activity? PMID- 17351861 TI - JPMorgan 25th annual healthcare conference. PMID- 17351862 TI - JPMorgan 25th annual healthcare conference. R&D at Merrimack, Inotek and Gemin X. PMID- 17351863 TI - JPMorgan 25th annual healthcare conference. Pipelines from NovaCardia, Quark Biotech, Raven Biotechnologies and Serenex. PMID- 17351864 TI - Respiratory Viruses of Animals Causing Disease in Humans--Keystone Symposium. PMID- 17351865 TI - Gastrointestinal Cancers--2007 symposium. Multidisciplinary approaches to the prevention, diagnosis and therapy of GI cancers. PMID- 17351866 TI - Second-Generation Pharmaceutical Proteins-EUFEPS Workshop on Optimizing Biotech Medicines. PMID- 17351867 TI - Drug Safety and Pharmacovigilance--second annual marcus evans conference. PMID- 17351868 TI - Antibody Engineering--IBC's 17th annual international conference. Antibody engineering and immunotherapeutics for the 21st century. PMID- 17351869 TI - Translating Depression and Anxiety Therapeutics--a marcus evans conference. Facilitating the transition from late-stage preclinical research to early development. PMID- 17351870 TI - Protein Engineering for Biotherapeutics--IBC's second annual conference. Developing and improving next generation biotherapeutics. PMID- 17351871 TI - Menopause Pharmacotherapeutic Development--CBI's second annual conference. PMID- 17351872 TI - Therapeutic success via targeted approaches and strategic partnerships with clinical laboratories. AB - The future of personalized medicine and the biopharmaceutical industry may lie in the close interaction between drug developers and clinical laboratories. The output of the Human Genome Project and other basic research into various diseases is generating data on individual variation in the treatment responses of patients; the biopharmaceutical industry and clinical laboratories will be expected to use this information to identify those patients who are best able to respond to a particular targeted therapy. Strategic partnerships between drug companies and clinical laboratories will be the centerpiece of this new era of medical treatment, providing higher-resolution diagnostics as well as more efficacious and safer treatment options. PMID- 17351873 TI - AMPA receptor potentiators as cognitive enhancers. AB - With an aging population, cognitive decline as a result of aging, Alzheimer's disease and other neurological conditions has become a major problem. Many of the current medications (eg, acetylcholinesterase inhibitors) for cognitive disorders show limited efficacy and are effective only in certain populations. Several other pharmacological pathways are therefore being explored in an attempt to develop superior medications. Glutamate and glutamate receptors are well recognized to play a key role in long-term potentiation (LTP), a process that is believed to underlie memory formation. Glutamate antagonists have been demonstrated to block LTP and to disrupt memory in both rodents and humans. Based on these data, it is not surprising that boosting glutamatergic transmission has been explored as a means of enhancing cognition. AMPA (alpha-amino-3-hydroxy-5 methyl-4-isoxazole propionic acid) receptors have been demonstrated to control fast synaptic transmission. Several classes of AMPA receptor potentiators have been described in the last decade. These molecules bind to allosteric sites on AMPA receptors, slow desensitization and thereby enhance signaling through the receptors. Some AMPA receptor potentiator agents have been explored in rodent models and are now entering clinical trials. Research complexity for these agents arises from the multiple AMPA receptor subtypes on which the molecules can act differentially, as well as from the distribution of AMPA receptors and the difficulty in studying cognition in naive rodents. Nevertheless, boosting Ca(2+) flux through the AMPA receptor, and enhancing LTP and downstream pathways may provide a novel approach to the treatment of cognitive deficits. PMID- 17351874 TI - Drug evaluation: Vilazodone--a combined SSRI and 5-HT1A partial agonist for the treatment of depression. AB - Vilazodone is a combined selective serotonin reuptake inhibitor (SSRI) and a 5 HT(1A) receptor partial agonist that is being developed by Clinical Data Inc for the treatment of depression. In preclinical studies, vilazodone compared favorably to other antidepressants such as paroxetine and fluoxetine. Orally administered vilazodone inhibited ultrasonic vocalization in the rat after electrical foot shock (a model of anxiolytic activity). Yet, in the forced swimming test model of depression in rats, vilazodone administered intraperitoneally was active at 1 mg/kg but not at 3 or 10 mg/kg. During clinical trials, vilazodone completely abolished REM sleep for 8 h and demonstrated antidepressant efficacy that was equal to that of current antidepressant therapeutics. The author concludes that the success of vilazodone as an effective antidepressant agent will depend on whether the drug can produce a more rapid antidepressant effect than other SSRI agents, or if specific genetic markers of patients can be associated with clinical efficacy. PMID- 17351878 TI - [What makes "Head-and-Neck-Cancers" recur: Tumorinvasion "revisited"]. AB - Head and neck squamous cell carcinomas (HNSCC) are common cancers with a relatively poor prognosis. Locoregionale recurrences are regularly encountered and associated with a detrimental outcome. Studies of the last few years report that not only tumor staging and grading influence locoregional control but also histologic and biological markers. One such histological marker is coined "worst pattern of invasion". It describes a histologic growth pattern consisting of invading tumor cell islands and strands that are dispatched from the invasion front (POI typ 4 and 5). Additional features of invasion are perineural invasion and extracapsular nodal extension. Besides histological markers there are molecular characteristics that include the expression of gene families involved in extracellular matrix degradation. The data suggest that head and neck cancers differ with respect to their invasive growth capacity and thus their ability to generate locoregionale recurrences. It appears that locoregionale control is a consequence of this growth pattern. This may explain, why in recent clincial studies the prognostic marker "pattern-of-invasion" outweights even such well established prognosticators such as "surgical margins". PMID- 17351880 TI - [Modern thyroidectomy and their German medical fee-accounting]. PMID- 17351881 TI - [Occupational head and neck cancer: Part II: Not-registered occupational diseases]. AB - Substances such as cement dust, polycyclic aromatic carbonhydrates (PAC), diesel exhaust and lubricatant cooling may contribute to the formation of cancer, but are not yet recognized as to be causing occupational cancer. By decree, these diseases can be recognized for compensation when there is enough new evidence for causality. The knowledge about these conditions is crucial for judgement. The technical supervisory board of the Employer's Liability Insurance Association should be asked to report information about the working place concentration of the accused substances before a decision can be made, because life-style factors (alcohol, smoking, nutrition) may contribute also. PMID- 17351882 TI - A new non-randomized model for analysing sensitive questions with binary outcomes. AB - We propose a new non-randomized model for assessing the association of two sensitive questions with binary outcomes. Under the new model, respondents only need to answer a non-sensitive question instead of the original two sensitive questions. As a result, it can protect a respondent's privacy, avoid the usage of any randomizing device, and be applied to both the face-to-face interview and mail questionnaire. We derive the constrained maximum likelihood estimates of the cell probabilities and the odds ratio for two binary variables associated with the sensitive questions via the EM algorithm. The corresponding standard error estimates are then obtained by bootstrap approach. A likelihood ratio test and a chi-squared test are developed for testing association between the two binary variables. We discuss the loss of information due to the introduction of the non sensitive question, and the design of the co-operative parameters. Simulations are performed to evaluate the empirical type I error rates and powers for the two tests. In addition, a simulation is conducted to study the relationship between the probability of obtaining valid estimates and the sample size for any given cell probability vector. A real data set from an AIDS study is used to illustrate the proposed methodologies. PMID- 17351883 TI - A DID analysis of the impact of health insurance reform in the city of Hangzhou. AB - The purpose of this study is to examine the impact of the 2003 reform of the health insurance system (in particular, the reduction in the co-payment amount) on the consumption of inpatient medical services in the city of Hangzhou using a differences-in-difference (DID) empirical strategy. The results confirm that private-sector employees (PSEs) (who were much more directly affected by the 2003 reform) were much more responsive to the reform than government employees. The growth rate of overall inpatient expenditures of PSEs (including retirees) increased by 26.4 percentage points more than that of government employees, which implies a relatively high (in absolute magnitude) price elasticity of demand for inpatient care of -1.10. Moreover, the growth rate of overall inpatient expenditures of currently employed PSEs increased by 37 percentage points more than that of government employees. Thus, the reform was effective in increasing PSEs' consumption of inpatient medical services, thereby reducing inter occupational inequities. However, a gap still exists between government employees and PSEs in their consumption of inpatient medical services, and thus further reforms of the system (for example, further reductions in inter-occupational inequities) are needed. PMID- 17351884 TI - Sur model with spatial effects: an application to mental health expenditure. AB - This study analyses, through the adoption of a seemingly unrelated regression approach, the temporal evolution of policy interactions among local authorities in England when allocating mental health resources. This new approach in health economics may shed light on the degree of interdependence between adjacent municipalities at a specific point in time (e.g. before, during, or after a change in policy), exploiting the information carried by the panel, rather than that of a single cross-section. PMID- 17351885 TI - Simultaneous determination of myo-inositol and scyllo-inositol by MEKC as a rapid monitoring tool for inositol levels. AB - A simple and rapid MEKC method was developed for the simultaneous determination of myo-inositol, scyllo-inositol, and glucose. Prior to electrophoretic separation, the nonfluorescent inositols and glucose were derivatized by N methylisatoic anhydride at 25 degrees C for 10 min so that they could be detected by a fluorescence detector during separation. The good separation with high efficiency by MEKC was achieved in 13 min with a glycine buffer containing SDS and PEG 4000. Several parameters affecting the separation were studied, including the pH of BGE, the concentrations of glycine, SDS, and PEG 4000, and the applied voltage. Using glycerol as an internal standard, the linear ranges of the method for myo-inositol, scyllo-inositol, and glucose were 0.03-10, 0.01-5, and 0.05-20 mM; the concentration LODs of myo-inositol, scyllo-inositol, and glucose were 0.020, 0.0078, and 0.026 mM, respectively. The method was applied to analyze extracellular myo-inositol and glucose in the microdialysates from rat brain cortex of ischemia animal model and intracellular myo-inositol and scyllo inositol in the rat brain extract. PMID- 17351886 TI - Protein expression profile in the striatum of rats with methamphetamine-induced behavioral sensitization. AB - Repeated administration of methamphetamine (MAP) results in an increased behavioral response to the drug during subsequent exposure. This phenomenon is called behavioral sensitization. Sensitization is an enduring phenomenon, and suggests chronic alterations in neuronal plasticity. MAP-induced sensitization has been proposed and widely investigated as an animal model of MAP psychosis and schizophrenia. However, little is known about the molecular mechanisms underlying MAP-induced sensitization. 2-DE-based proteomics allows us to examine global changes in protein expression in complex biological systems and to propose hypotheses concerning the mechanisms underlying various pathological conditions. In the present study, we examined protein expression profiles in the striatum of MAP-sensitized rats using 2-DE-based proteomics. Repeated administration of MAP (4.0 mg/kg, once a day, intraperitoneal (i.p.)) for 10 days significantly augmented the locomotor response to an MAP challenge injection (1.0 mg/kg, i.p.) on day 11. This enhanced activity was maintained even after a week of drug abstinence. 2-DE analysis revealed 42 protein spots were differentially regulated in the striatum of MAP-sensitized rats compared to control. Thirty-one protein spots were identified using MALDI-TOF, including synapsin II, synaptosomal associated protein 25 (SNAP-25), adenylyl cyclase-associated protein 1 (CAP1), and dihydropyrimidinase-related protein 2 (DRP2). These proteins can be related to underlying mechanisms of MAP-induced behavioral sensitization, indicating cytoskeletal modification, and altered synaptic function. PMID- 17351887 TI - Contamination of nuclear fractions with plasma membrane lipid rafts. AB - Subcellular fractionation is central to a range of cell biological, biochemical and proteomic studies. Purification of nuclear-enriched fractions is critical for studies on nuclear structure and function. Here we show that detergent-based nuclear isolation methods cause the redistribution of proteins associated with plasma membrane lipid rafts into nuclear fractions. The glycosyl phosphatidylinositol (GPI)-anchored prion protein (PrP(C)) and a GPI-anchored construct of angiotensin converting enzyme (GPI-ACE), as well as the lipid raft markers flotillin-1 and -2, were present in the nuclear fractions derived using three different subcellular fractionation protocols. Incubation of intact cells with bacterial phosphatidylinositol-specific phospholipase C (PI-PLC), which cleaves GPI-anchored proteins from the cell surface, significantly reduced the amount of PrP(C) and GPI-ACE in the nuclear fraction. Buoyant sucrose density gradient centrifugation in the presence of Triton X-100 of the nuclear fraction resulted in a significant proportion of the GPI-anchored proteins being recovered in the low density lipid raft fractions. These data indicate that the nuclear fraction isolated using such subcellular fractionation protocols is contaminated with components of plasma membrane lipid rafts and raises questions as to the integrity of the nuclear fraction isolated by such protocols for use in detailed cell biological studies and proteomics analysis. PMID- 17351888 TI - Yeast proteome map (update 2006). AB - To improve the potential of two-dimensional gel electrophoresis for proteomic investigations in yeast we have undertaken the systematic identification of Saccharomyces cerevisiae proteins separated on 2-D gels. We report here the identification of 187 novel protein spots. They were identified by two methods, mass spectrometry and gene inactivation. These identifications extend the number of protein spots identified on our yeast 2-D proteome map to 602, i.e. nearly half the detectable spots of the proteome map. These spots correspond to 417 different proteins. The reference map and the list of identified proteins can be accessed on the Yeast Protein Map server (www.ibgc.u-bordeaux2.fr/YPM). PMID- 17351889 TI - Methods for the purification of ubiquitinated proteins. AB - Post-translational protein modification by the covalent conjugation of ubiquitin, originally implicated as a signal for proteolytic degradation by 26S proteasome, has now been realised to play important roles in the regulation of almost all biological processes in eukaryotes. In order to understand these processes in greater detail there is a requirement for techniques that can purify mixtures of ubiquitin-conjugated proteins, as a prerequisite to their identification and characterisation. Here we review the methods that have been applied to the bulk purification of ubiquitinated proteins and discuss their applications in proteomic analyses of the 'ubiquitome'. PMID- 17351890 TI - WITHDRAWN: An improved direct pumping approach to eliminate sample bias in capillary electrokinetic injection. AB - The EOF pump was successfully used as a means of introducing samples into a capillary system. An improved sample injection device has been developed using a Teflontrade mark union (TU) to link the two capillaries together. The capillary applied high voltage served as the EOF pump to pull the liquid inside while the other one served the purposes of isolating the electric field. Using the bias degree (BD) and SD of bias (SDB), it was possible to quantitatively determine the sampling bias and evaluate the effectiveness of injection approaches in bias elimination. Several related factors were evaluated, and it was found that TU approach could fully eliminate the bias under the optimal conditions. The fracture did not affect the efficiency, leak, or dilute the sample significantly. This approach was effective under both normal and reverse EOF situations and adapted to real samples. Finally, a TU method using grounded injection electrode was proposed and shown to be suitable for samples with low conductivity and high injection voltage. PMID- 17351891 TI - On-line coupling of SPE and CE-MS for peptide analysis. AB - An on-line SPE-CE-MS system has been developed for the analysis of peptides. Analytes are preconcentrated using a C(18) microcolumn (5 x 0.5 mm id), and then introduced into the CE system via a valve interface. The CE system with a Polybrene-poly(vinylsulfonate) bilayer coated capillary is combined with an ion trap mass spectrometer via ESI using a coaxial sheath-liquid sprayer. The on-line coupling of the SPE and CE step by the valve interface is advantageous because it allows an independent functioning of the system parts. Optimization of the SPE-CE system was performed using UV detection. Subsequently, the SPE-CE system has been coupled to the ion-trap mass spectrometer. Test solutions with enkephalin peptides (50 ng/mL) were used for evaluation of system performance. Repeatability of effective mobility and peak area ratio of the two enkephalins were within 1.2% and 9% RSD, respectively. The analysis of 1:1 v/v diluted cerebrospinal fluid samples spiked with enkephalin peptides showed detection limits (S/N = 3) in the range of 1.5-3 ng/mL (around 5 nM), which were similar to those obtained for enkephalin test solutions. Moreover, the potential of the on-line SPE-CE-MS system was demonstrated by the analysis of a cytochrome C digest. Some hydrophilic peptides did not show sufficient retention on the SPE column, and were lost during preconcentration. Nonetheless, positive identification of the protein was achieved, indicating the feasibility of the system for proteomics. PMID- 17351892 TI - An electrical pumping approach to eliminate sample bias in capillary electrokinetic injection. AB - A general pumping injection (PI), which involves the use of two capillaries with different diameters, was taken to evaluate systematically the effects on eliminating sample bias associated with the electrokinetic injection process in CE. One end of the separation capillary of the smaller diameter was inserted into another pumping capillary of larger diameter. When a high voltage was applied to the pumping capillary, the EOF generated inside will act as a pump to drive the solution stream in the separation capillary. The results have demonstrated that PI is suitable for both normal and reverse EOF situations. Second, the bias degree (BD) and SD of bias we presented were used to evaluate the degree of the bias under different conditions, and the factors of bias elimination have been investigated. Under optimal conditions, the bias was satisfactorily eliminated by PI. This EOF pumping system was successfully applied to the analysis of samples in CEC for a bias-free injection. Moreover, this two-capillary pumping system did not significantly affect the EOF, current, and the column efficiency of the separation process. Finally, a PI with grounded electrode was proposed and shown to be suitable for samples with low conductivity and ions with different mobility. PMID- 17351893 TI - Multivariate analysis of 2-DE protein patterns--practical approaches. AB - Practical approaches to the use of multivariate data analysis of 2-DE protein patterns are demonstrated by three independent strategies for the image analysis and the multivariate analysis on the same set of 2-DE data. Four wheat varieties were selected on the basis of their baking quality. Two of the varieties were of strong baking quality and hard wheat kernel and two were of weak baking quality and soft kernel. Gliadins at different stages of grain development were analyzed by the application of multivariate data analysis on images of 2-DEs. Patterns related to the wheat varieties, harvest times and quality were detected on images of 2-DE protein patterns for all the three strategies. The use of the multivariate methods was evaluated in the alignment and matching procedures of 2 DE gels. All the three strategies were able to discriminate the samples according to quality, harvest time and variety, although different subsets of protein spots were selected. The explorative approach of using multivariate data analysis and variable selection in the analyses of 2-DEs seems to be promising as a fast, reliable and convenient way of screening and transforming many gel images into spot quantities. PMID- 17351894 TI - Comparison of atmospheric pressure photoionization and ESI for CZE-MS of drugs. AB - The performance of atmospheric pressure photoionization (APPI) and ESI for CZE was compared using a set of seven drugs (basic amines, quaternary amines and steroids) and four different BGEs. The influence of volatile and nonvolatile BGEs of acidic and neutral pH on the MS responses of test compounds was evaluated by infusion of test solutions into the respective ion sources, and by actual CZE-MS experiments. The infusion experiments indicate that sodium phosphate buffers cause ionization suppression in ESI-MS, although for the amines the suppression was modest (25-60% signal reduction). By contrast, APPI-MS responses were not affected by nonvolatile BGEs. With phosphate buffers, ESI-MS responses for the basic amines were still a factor 3-13 higher than the APPI-MS signals, whereas the steroids yielded similar responses in ESI-MS and APPI-MS. The quaternary amines could readily be detected in ESI-MS, but detection in APPI-MS required specific interface conditions. Using typical CZE-APPI-MS settings, quaternary amines remained undetected. Remarkably, the S/Ns observed in CZE-ESI-MS for the test compounds, were generally similar when using volatile and nonvolatile BGEs. For basic compounds, the S/Ns obtained in CZE-ESI-MS were a factor 2-5 higher than in CZE-APPI-MS, whereas steroids yielded equal S/Ns in both methods. Overall, it is concluded that when using relatively low BGE concentrations, the sensitivity of ESI-MS detection in CZE is more favorable than APPI-MS detection, even when nonvolatile BGEs are employed. PMID- 17351895 TI - Accelerated multiple-pass moving average: a novel algorithm for baseline estimation in CE and its application to baseline correction on real-time bases. AB - We present a novel algorithm for baseline estimation in CE. The new algorithm which we have named as accelerated multiple-pass moving average (AMPMA) is combined to three preexisting low-pass filters, spike-removal, moving average, and multi-pass moving average filter, to achieve real-time baseline correction with commercial instrumentation. The successful performance of AMPMA is demonstrated with simulated and experimental data. Straightforward comparison of experimental data clearly shows the improvement AMPMA provides to the linear fitting, LOD, and accuracy (absolute error) of CE analysis. PMID- 17351896 TI - Global protein expression profiling of budding yeast in response to DNA damage. AB - Exposure to DNA-damaging agents can activate cell cycle checkpoint and DNA repair processes to ensure genetic integrity. Such exposures also can affect the transcription of many genes required for these processes. In the budding yeast Saccharomyces cerevisiae, changes of global gene expression as a result of a DNA damaging agent were previously identified by using DNA chip technology. DNA microarray analysis is a powerful tool for identifying genes whose expressions are changed in response to environmental changes. Transcriptional levels, however, do not necessarily reflect cellular protein levels. Green fluorescent protein (GFP) has been widely used as a reporter of gene expression and subcellular protein localization. We have used 4156 yeast strains expressing full length, chromosome-tagged GFP fusion proteins to monitor changes of protein levels in response to the DNA-damaging agent, methyl methanesulphonate (MMS). Through flow cytometry, we identified 157 proteins whose levels were increased at least three-fold following treatment with MMS. Of 157 responsible genes, transcriptions of 57 were previously not known to be induced by MMS. Immunoblot experiments with tandem affinity-tagged yeast strains under the same experimental conditions confirmed these newly found proteins as inducible. These results suggest, therefore, that the 57 protein expressions are regulated by different mechanisms, such as post-translational modifications, and not by transcriptional regulation. PMID- 17351897 TI - Handling drop-out in longitudinal clinical trials: a comparison of the LOCF and MMRM approaches. AB - This study compares two methods for handling missing data in longitudinal trials: one using the last-observation-carried-forward (LOCF) method and one based on a multivariate or mixed model for repeated measurements (MMRM). Using data sets simulated to match six actual trials, I imposed several drop-out mechanisms, and compared the methods in terms of bias in the treatment difference and power of the treatment comparison. With equal drop-out in Active and Placebo arms, LOCF generally underestimated the treatment effect; but with unequal drop-out, bias could be much larger and in either direction. In contrast, bias with the MMRM method was much smaller; and whereas MMRM rarely caused a difference in power of greater than 20%, LOCF caused a difference in power of greater than 20% in nearly half the simulations. Use of the LOCF method is therefore likely to misrepresent the results of a trial seriously, and so is not a good choice for primary analysis. In contrast, the MMRM method is unlikely to result in serious misinterpretation, unless the drop-out mechanism is missing not at random (MNAR) and there is substantially unequal drop-out. Moreover, MMRM is clearly more reliable and better grounded statistically. Neither method is capable of dealing on its own with trials involving MNAR drop-out mechanisms, for which sensitivity analysis is needed using more complex methods. PMID- 17351898 TI - Identification of a novel human papillomavirus (HPV97) related to HPV18 and HPV45. AB - Human papillomavirus (HPV) type 97 was identified and the genome was cloned from cervicovaginal cells of a Costa Rican woman with a normal Pap smear. The HPV97 L1 open reading frame (ORF) was most closely related to HPV45 (84% identity) and HPV18 (79% identity), placing it into the high-risk alpha7 species. Ectopic expression of the HPV97 E6 and E7 proteins significantly decreased steady state p53 and pRb levels using an in vitro cotransfection assay, respectively. These data suggest that HPV97 shares a most recent common ancestor with HPV18 and HPV45 and should be evaluated in cancer specimens from different geographic populations. PMID- 17351899 TI - Cell exfoliation in the human colon: myth, reality and implications for colorectal cancer screening. AB - Colonocyte exfoliation in the human colon constitutes a unique mechanism of cell population control that can undergo significant changes under different physiological and pathological conditions. Being closely related to the apoptosis and anoikis, cell exfoliation from colonic epithelium appears to be a relatively rare event in normal conditions, but its rate dramatically increases in neoplasia, when cell removal by apoptosis in situ does not function properly. Several studies show that significant numbers of exfoliated colonocytes are not lost in the faecal contents of the gut, but retained in the mucocellular layer overlying colonic mucosa. Recent observations allow hypothesizing that the mucocellular layer containing exfoliated colonocytes may gradually migrate distally, eventually leading to the accumulation of the cells exfoliated from malignant colorectal tumours on the surface of the rectal mucosa. Implications of exfoliated colonocyte analysis to colorectal cancer screening and early diagnosis are discussed. PMID- 17351900 TI - No evidence for association of NOD2 R702W and G908R with colorectal cancer. AB - Polymorphisms in nucleotide oligomerization domain 2 gene (NOD2) have been associated with increased susceptibility to Crohn's disease. Recently, possible association of the NOD2 variants R702W, G908R and 3020insC with colorectal cancer (CRC) has been studied among Polish, Greek, Finnish and New Zealand Caucasian CRC patients, but the results have been controversial. In the Polish study, 3020insC alone, and in the Greek study all the 3 variants, showed association with CRC. In a study from New Zealand, R702W appeared to increase CRC risk. In addition, the combined frequencies of the 3 variants were significantly elevated in CRC patients compared with healthy controls. We have previously shown that NOD2 3020insC is not associated with increased CRC risk in Finland. In the current study, we have genotyped the R702W and G908R in a population-based series of 1,042 CRC patients and in 508 healthy controls to study the possible contribution of these variants to CRC predisposition. Of the CRC patients, 953 were successfully analyzed. R702W and G908R were equally, frequently seen in CRC patients and controls (R702W: 2.2% vs. 2.1%; G908R: 0.3% vs. 0.2%). No associations between NOD2 variants and clinical characteristics were observed. Our results indicate that NOD2 variants R702W, G908R and 3020insC do not predispose to CRC in Finland. Environmental or additional genetic factors may play a role in CRC development in NOD2 variant carriers. Further work is necessary to establish the possible role of NOD2 variants in CRC predisposition. PMID- 17351901 TI - Mannose-binding lectin and gastric cancer. PMID- 17351902 TI - RNAse A-like enzymes in serum inhibit the anti-neoplastic activity of siRNA targeting polo-like kinase 1. AB - Down-modulation of target molecules in tumor cells by small interfering (si) RNAs is a promising anti-cancer strategy. A major challenge of this approach is the loss of silencing activity of the siRNAs in vivo. Our study aimed at investigating the influence of the serum compartment on the anti-tumor activity of siRNA directed against Polo-like kinase 1 (Plk1), a mitosis-associated serine/threonine kinase. The data showed that siRNA-induced suppression of Plk1 expression effectively reduced the viable cell mass and increased apoptosis in several cancer cell lines. Preincubation of the siRNA in human serum led to shortening of the siRNA as well as loss of its Plk1 silencing and anti-tumor activity. This loss of activity was prevented by inhibition of RNAse A-like enzymes. These data indicate that the anti-neoplastic effect of siRNAs declines upon incubation in human serum. This loss of anti-neoplastic activity can be prevented by inhibition of their degradation by RNAse A-like enzymes. This may have important implications for the development of a human therapeutic application of siRNAs. PMID- 17351903 TI - Risk of second cancer after chronic lymphocytic leukemia. AB - Smoking is not considered a risk factor for chronic lymphocytic leukemia (CLL) yet increased lung cancer risk has been reported for these patients. Little data exist on the temporal variation in lung cancer risk after CLL, or its histological composition. We investigated the occurrence of second cancers in a large cohort of CLL patients with particular emphasis on lung cancer and its major subtypes. We followed all patients diagnosed with CLL in Denmark in the period 1943-2003 (n = 12,373) for the occurrence of second cancers. The relative risk was expressed as the standardized incidence ratio (SIR), i.e. the ratio of observed to expected number of cancers, based on incidence rates for the Danish population. During follow-up 1,105 cancers occurred among the CLL patients (SIR = 1.59 (95% CI 1.50-1.69)). SIR for all cancers combined remained elevated more than 10 years after CLL (SIR = 1.80 (1.56-2.08)). Lung cancer occurred in 141 patients (SIR = 1.61 (1.37-1.90)). The relative risk of lung cancer did not vary by gender, or time of follow-up, but was higher in younger (SIR(<60 years) = 2.22 (1.62-3.06)) than in older (SIR(70-79 years) = 1.21 (0.88-1.68)) age-groups. Elevated risks were observed for adenocarcinoma (SIR = 2.20 (1.57-3.08)) and squamous cell carcinoma (SIR = 1.52 (1.06-2.17)) of the lung. We speculate that shared genetic risk factors may explain the accumulation of lung and other cancers in CLL patients. PMID- 17351904 TI - Biomarkers in drug development: friend or foe? A personal reflection gained working within oncology. AB - Hopes and expectations for the use and utility of new, emerging biomarkers in drug development have probably never been higher, especially in oncology. Biomarkers are exalted as vital patient selection tools in an effort to target those most likely to benefit from a new drug, and so to reduce development costs, lessen risk and expedite developments times. It is further hoped that biomarkers can be used as surrogate endpoints for clinical outcomes, to demonstrate effectiveness and, ultimately, to support drug approval. However, I perceive that all is not straightforward, and, particularly in terms of the promise of accelerated drug development, biomarker strategies may not in all cases deliver the advances and advantages hoped for. PMID- 17351905 TI - Assessing the clinical utility of agoraphobia in the context of panic disorder. AB - In the DSM-IV, a panic disorder (PD) diagnosis includes specification of agoraphobia, which is primarily an index of situational avoidance due to fear of panic. No other anxiety diagnosis requires specification of level of avoidance. This raises the question as to whether agoraphobia provides unique information beyond the core features of PD (i.e., panic attacks and panic-related worry). The incremental validity of agoraphobia, defined using DSM-IV specifiers versus level of situational avoidance, was examined in relation to the expression and treatment of PD (N=146). Analyses indicate that agoraphobia status adds uniquely to the prediction of PD symptoms, impairment, and response to treatment. However, level of situational avoidance, defined either as a continuous or dichotomous variable, appears to have greater utility compared to the DSM-IV method of classifying agoraphobia. In summary, the agoraphobia specifier seems to have clinical utility but this could be improved by focusing on a dimensional assessment of situational avoidance. PMID- 17351906 TI - Microevolution in genomic short sequence repeats of Candida albicans in non neutropenic patients. AB - The genome of the yeast Candida albicans harbours many genomic short sequence repeats (SSRs). These are stable upon transition of colonization to infection in immune-compromised patients. We show here that in non-neutropenic patients this transition may coincide with variation in several of the SSRs. This may have implications for stage-specific expression of C. albicans pathogenicity factors. PMID- 17351907 TI - Role of Gts1p in regulation of energy-metabolism oscillation in continuous cultures of the yeast Saccharomyces cerevisiae. AB - Energy-metabolism oscillation (EMO) in an aerobic chemostat culture of yeast is basically regulated by a feedback loop of redox reactions in energy metabolism and modulated by metabolism of storage carbohydrates. In this study, we investigated the role of Gts1p in the stabilization of EMO, using the GTS1 deleted transformant gts1Delta. We found that fluctuations in the redox state of the NAD co-factor and levels of redox-regulated metabolites in glycolysis, especially of ethanol, are markedly reduced in amplitude during EMO of gts1Delta, while respiration indicated by the oxygen uptake rate (OUR) and energy charge is not so affected throughout EMO in gts1Delta. Further, the transitions of the levels of OUR, NAD(+) : NADH ratio and intracellular pH between the two phases were apparently retarded compared with those in the wild-type, suggesting attenuation of EMO in gts1Delta. Furthermore, the mRNA levels of genes encoding enzymes for the synthesis of trehalose and glycogen are fairly reduced in gts1Delta, consistent with the decreased synthesis of storage carbohydrates. In addition, the level of inorganic phosphate, which is required for the reduction of NAD(+) and mainly supplied from trehalose synthesis, was decreased in the early respiro-fermentative phase in gts1Delta. Thus, we suggested that the deletion of GTS1 as a transcriptional co-activator for these genes inhibited the metabolism of storage carbohydrates, which causes attenuation of the feedback loop of dehydrogenase reactions in glycolysis with the restricted fluctuation of ethanol as a main synchronizing agent for EMO in a cell population. PMID- 17351908 TI - Osmoresistant yeast Zygosaccharomyces rouxii: the two most studied wild-type strains (ATCC 2623 and ATCC 42981) differ in osmotolerance and glycerol metabolism. AB - The yeast Zygosaccharomyces rouxii is known for its high tolerance to osmotic stress, which is thought to be caused by sets of specific genes. Relatively few Z. rouxii genes have been identified so far, all of them having homologues in Saccharomyces cerevisiae; none of them was Z. rouxii-specific. Most of the known Z. rouxii genes were isolated from two wild-type strains, ATCC 2623 and ATCC 42981. In this study, we compared these two strains with regard to some of their morphological, physiological and genomic properties. Important differences were found in their salt tolerance and assimilation of glycerol and karyotype; slight differences were also present in their cell morphology. The ATCC 42981 strain showed a higher resistance to salts, higher glycerol production and, unlike ATCC 2623, was able to assimilate glycerol. Under conditions of osmotic stress, the glycerol production in both Z. rouxii strains was much lower than in a S. cerevisiae S288c culture, which suggested the presence of a system that efficiently retains glycerol inside Z. rouxii cells. The karyotype analysis revealed that ATCC 42981 cells contain more chromosomes and have a bigger genome size than those of ATCC 2623. PMID- 17351909 TI - Cloning, sequencing and characterization of the alpha-aminoadipate reductase gene (LYS2) from Saccharomycopsis fibuligera. AB - The gene putatively encoding alpha-aminoadipate reductase (AAR) was isolated successfully by degenerate PCR and chromosome walking, based on cassette PCR methods, from the dimorphous yeast Saccharomycopsis fibuligera PD70 and was named SfLYS2. Sequence analysis revealed that it contained a putative open reading frame (ORF) of 4161 bp and encoded a polypeptide of 1386 amino acids. The deduced translation product shared an identity of 53% and 51% to the Lys2p homologues of Candida albicans and Saccharomyces cerevisiae, respectively. An atypical TATA box and a GCN4-box element were found in the 5'-upstream region. Genomic Southern hybridization suggested the presence of a single locus of SfLYS2 in the S. fibuligera genome. Expression of the ORF of SfLYS2 in a lys2(-) strain of S. cerevisiae could functionally complement the lysine mutant of the S. cerevisiae strain. S. fibuligera could use lysine as the sole nitrogen source but its growth was inhibited on the alpha-aminoadipate (AA) medium. Approximately 90% of the mutants of S. cerevisiae resistant to AA are lysine auxotrophs; in contrast all the mutants of S. fibuligera resistant to AA recovered in this work were not lysine auxotrophs. PMID- 17351910 TI - Cloning, characterization and functionality of the orotidine-5'-phosphate decarboxylase gene (URA3) of the glycolipid-producing yeast Candida bombicola. AB - Candida bombicola is a yeast species known to synthesize glycolipids. Although these glycolipids find several industrial, cosmetic and pharmaceutical applications, very little is known about the genetics of C. bombicola. A basic tool for genetic study and modification is the availability of an efficient transformation and selection system. In order to develop such a system, the URA3 gene of Candida bombicola was isolated using degenerate PCR and genomic walking. The gene encodes for an enzyme of 262 amino acids and shows high homology with the known orotidine-5'-phosphate decarboxylases of several other yeast species. The functionality of the gene was proved by complementation of a URA3-negative Saccharomyces cerevisiae strain. PMID- 17351911 TI - Micromere-derived signal regulates larval left-right polarity during sea urchin development. AB - The micromeres (Mics) lineage functions as a morphogenetic signaling center in early embryos of sea urchins. The Mics lineage releases signals that regulate the specification of cell fates along the animal-vegetal and oral-aboral axes. We tested whether the Mics lineage might also be responsible for differentiation of the left-right (LR) axis by observing of the placement of the adult rudiment, which normally forms only on the left side of the larvae, after removal of the Mics lineage. When all of the Mics lineage were removed from embryos of the regular sea urchin Hemicentrotus pulcherrimus between the 16- and 64-cell stages, the LR placement of the rudiment became randomized. However, the immediate retransplantation of the Mics rescued the normal LR placement of the rudiment, indicating that the Mics lineage releases a signal that specifies LR polarity. Additionally, we investigated whether the specification of LR polarity of whole embryos in the indirect-developing sea urchin H. pulcherrimus is affected by LiCl exposure, which disturbs the establishment of LR asymmetry in a direct-developing sea urchin. Larvae derived from normal animal caps combined with LiCl-exposed Mics descendants were defective in normal LR placement of the rudiment, suggesting that LiCl interferes with the Mics-derived signal. In contrast, embryos of two sand dollar species (Scaphechinus mirabilis and Astriclypeus manni) were resistant to alteration of LR placement of the rudiment by either removal of the Mics lineage or LiCl exposure. These results indicate that the Mics lineage is involved in specification of LR polarity in the regular sea urchin H. pulcherrimus, and suggest that LiCl impairs the normal LR patterning by affecting Mics-derived signaling. PMID- 17351912 TI - Protective effect of ethyl pyruvate on msP rat leukocytes damaged by alcohol intake. AB - Alcohol consumption for long periods negatively influences physiological functions of many cells, and leads to organ damage. Reactive oxygen and nitrogen species produced by ethanol metabolism cause adverse effects that might be alleviated by simultaneous treatment with various antioxidants. Here, the ability of ethyl pyruvate (EP) to reduce ethanol-induced oxidative stress was evaluated. Chemiluminescence studies show that EP has a higher capacity than pyruvate to scavenge hydrogen peroxide and superoxide anions. In order to evaluate whether EP can exert a protective effect against ethanol, rats were offered 10% ethanol in drinking burettes, containing or not different concentrations of EP (0.3%, 1% and 3%). The comet assay was employed to quantify the alcohol-induced DNA damage in rat lymphocytes. This test is a promising tool for the estimation of DNA damage at the single cell level. A significant protective effect of EP was observed in rat groups treated with this antioxidant, compared with those drinking only ethanol. Since EP has been shown to decrease the expression of numerous pro inflammatory mediators, the monocyte respiratory burst was evaluated. The activation of monocyte NADPH oxidase by phorbol esters (PMA) showed that superoxide anion production was higher in the ethanol group than in the control group. The presence of EP considerably reduced superoxide anion production. In conclusion, hypotheses on possible mechanisms of action of EP on rat white blood cells are proposed. PMID- 17351913 TI - Curcumin reduces indomethacin-induced damage in the rat small intestine. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical medicine. Their utility is, however, often limited by the adverse effects they produce in the gastrointestinal tract. Oxidative stress has been shown to occur in the small intestine in response to the oral administration of indomethacin, an NSAID commonly used in toxicity studies. In view of this, the effect of curcumin, an agent with anti-oxidant properties, was evaluated on indomethacin-induced small intestinal damage in a rat model. Rats were pretreated with various doses of curcumin (20 mg kg(-1), 40 mg kg(-1) and 80 mg kg(-1)) before administering indomethacin at 20 mg kg(-1). Various parameters of oxidative stress and the extent of small intestinal damage produced by indomethacin, with and without pretreatment with curcumin, were measured. Macroscopic ulceration was found to occur in the small intestine in response to indomethacin. The viability of enterocytes from indomethacin-treated animals was significantly lower than those from control animals. Drug-induced oxidative stress was also evident as seen by increases in the levels of malondialdehyde and protein carbonyl and in activities of pro-oxidant enzymes such as myeloperoxidase and xanthine oxidase in indomethacin-treated rats. Concomitant decreases were seen in the activities of the antioxidant enzymes catalase and glutathione peroxidase in these animals. Pretreatment with curcumin was found to ameliorate these drug-induced changes. Thus, curcumin appears to hold promise as an agent that can potentially reduce NSAID-induced small intestinal damage. PMID- 17351914 TI - Electrophysiological study of infant and adult rats under acute intoxication with fluoroacetamide. AB - A study was conducted of acute intoxication of infant and adult Wistar rats with fluoroacetamide (FAA), an inhibitor of oxidative metabolism. FAA was administered orally to adult rats at 1/2 LD(50) and subcutaneously to infant rats at LD(100) or 1/10 LD(50). Electrocardiogram (ECG), respiration and motor activity were registered for 7 days. Clinical analysis of ECG and the heart rate variability (HRV) was carried out to assess the state of the vegetative nervous system. In adult rats, FAA caused marked disturbances in the activity of cardiovascular and respiratory systems, including the development of a potentially lethal acute cor pulmonale. Conversely, there were no significant changes of cardiac function and respiration in infant rats; they died because of extreme emaciation accompanied by retardation of development. In adult rats, bursts of associated cardiac and respiratory tachyarrhythmia, as well as regular high amplitude spasmodic sighs having a deca-second rhythm were observed. In both infant and adult rats, FAA caused short-term enhancement of humoral (metabolic) and sympathetic activities, followed by a gradual and stable predominance of parasympathetic influence on HRV. Under conditions of FAA inhibition of the tricarboxylic acid cycle, the observed physiological reactions may be explained by activation of alternative metabolic pathways. This is also supported by a lack of ontogenetically caused inhibition of spontaneous motor activity in infant rats poisoned with FAA, which highlights the significance of the alternative metabolic pathways for implementation of deca-second and minute rhythms and a lack of a rigid dependence of these rhythms upon activity of neuronal networks. PMID- 17351915 TI - Protective effect of diphenylmethyl selenocyanate against CCl4-induced hepatic injury. AB - Organoselenocyanates represent an important class of chemopreventive agent, which possess antioxidative, antimutagenic as well as cancer chemopreventive properties. The present study is an attempt to evaluate the protective effect of diphenylmethyl selenocyanate -- a synthetic organoselenocyanate against carbon tetrachloride (CCl(4))-induced hepatic damage in Swiss albino mice in vivo. Mice were pretreated with the Se-compound orally in a duration dependent manner (7 and 15 days) to observe its protective action against an acute toxic dose (24 h) of CCl(4) (single injection at a dose of 20 microl and 50 microl kg(-1) b.w.) that induced hepatic necrosis and caused DNA damage (strand breaks) in the hepatocytes. This study revealed that pretreatment with the Se-compound reduced the extent of massive hepatic necrosis in a duration dependent manner, but it had no modulatory effect on hepatocellular apoptosis caused by acute toxic doses of CCl(4). It was also found that the Se-compound could significantly (P < 0.01) prevent the CCl(4)-induced elevation of DNA damage in hepatocytes measured by comet assay in a duration dependent manner. So these findings will further strengthen the view that organoselenocyanate is an effective chemopreventive agent against acute hepatic damage, caused by halogenated alkanes such as CCl(4). PMID- 17351916 TI - Fertile triploid males: an uncommon case among hybrid vertebrates. AB - The endemic Iberian minnow Squalius alburnoides is a complex of fishes of hybrid origin including both males and females with distinct ploidy levels and varying proportions of the parental genomes. In this paper we demonstrated that in contrast to many vertebrate hybrid lineages the sperm of triploid hybrid males of S. alburnoides is viable and fully functional. Flow cytometry and analysis of sequences of a fragment of the beta-actin nuclear gene applied to progenitors and offspring evidenced that these males produced their sperm clonally, as already described for diploid hybrids. The presence of different types of fertile males (nonhybrid diploids with normal meiosis and both diploid and triploid hybrids) coupled with hybridogenetic meiosis in females endows this vertebrate complex with a high level of independence from other species and contributes to maintain its genetic variability. PMID- 17351917 TI - Apium graveolens modulates sodium valproate-induced reproductive toxicity in rats. AB - Sodium valproate (VPA), a common treatment of epilepsy and other diseases, is known to have severe toxic effects on testis both in experimental animals and in humans. The present study was designed to investigate the protective effect of Apium graveolens (AG) against the VPA-induced testis injury. Testicular toxicity was induced by the administration of VPA (500 mg/kg/day) once daily for 7 consecutive days. Protective group received daily doses (200 mg/kg/day) of AG crude extract for 23 days prior to VPA administration. VPA-induced reproductive toxicity was assessed based on the weight of testes, sperm analysis, and serum concentrations of sexual hormones. The relative weights of testes and epididymes and the sperm numbers viability were all decreased following the valproate administration. Testosterone levels dropped while follicle stimulating hormone (FSH) level increased following the drug administration. Severe histopathological changes in testis were observed such as degeneration of seminiferous tubules and depletion of germ cells. These biochemical and histological changes were also associated with alterations of oxidative stress markers. Levels of malondialdehyde have increased, while superoxide dismutase activity has decreased. Pretreatment with A. graveolens extract has effectively alleviated most of the VPA-induced effects suggesting a protective role of A. graveolens extract against experimental VPA-induced toxicity. Apigenin content was estimated and was shown as a major fraction of the A. graveolens extract. PMID- 17351918 TI - Four-helix bundle cavitein reveals middle leucine as linchpin. AB - A template-assembled de novo four-helix bundle is used to examine the hydrophobic effect within the bundle interior. Leu to Ala variants of the basis sequence GG EELLKKLEELLKKG were characterized by GuHCl denaturation, NMR dispersion, and N H/D exchange experiments. The results show that the middle leucine (L7) is imperative in maintaining bundle stability. The average leucine was found to contribute 1.8 kcal mol(-1) toward stability, whereas the middle leucines contribute 2.7 kcal mol(-1) each. Substituting alanine into the middle position (7) constitutes a striking 95% reduction of the overall cavitein stability. PMID- 17351919 TI - Dome set-up in urodynamics. PMID- 17351921 TI - Amplicon profiles in ovarian serous carcinomas. AB - Ovarian serous carcinoma is the most common and lethal type of ovarian cancer and its molecular etiology remains poorly understood. As an ongoing effort to elucidate the pathogenesis of ovarian serous carcinomas, we assessed the DNA copy number changes in 33 high-grade serous carcinomas and 10 low-grade serous tumors by using a genome-wide technique, single nucleotide polymorphism array, performed on affinity-purified tumor cells from fresh surgical specimens. Compared to low grade tumors, high-grade serous carcinomas showed widespread DNA copy number changes. The most frequent alterations were in loci harboring candidate oncogenes: cyclin E1 (CCNE1), AKT2, Notch3 and PIK3CA as well as in novel loci, including 12p13, 8q24, 12p13 and 12q15. Seven amplicons were selected for dual color fluorescence in situ hybridization analysis in approximately 90 high-grade serous carcinomas and 26 low-grade serous tumors, and a high level of DNA copy number gain (amplification) was found in CCNE1, Notch3, HBXAP/Rsf-1, AKT2, PIK3CA and chr12p13 occurring in 36.1%, 7.8%, 15.7%, 13.6%, 10.8% and 7.3% of high-grade serous carcinomas. In contrast, we did not observe high level of ERBB2 amplification in any of the samples. Low-grade tumors did not show DNA copy number gain in any of the loci, except in 2 (8%) of 24 low-grade tumors showing low copy number gain in the Notch3 locus. Taken together, our results provide the first comprehensive analysis of DNA copy number changes in highly pure ovarian serous carcinoma. These findings may have important biological and clinical implications. PMID- 17351922 TI - Maintenance of certification - an update. PMID- 17351923 TI - Clinical outcomes three years after PLAATO implantation. AB - BACKGROUND: The percutaneous left atrial appendage transcatheter occlusion system (PLAATO) is an alternative to coumadin in patients with atrial fibrillation (AF) and contraindications to anticoagulation. It appears to be protective against stroke in intermediate follow-up studies. HYPOTHESIS: The PLAATO system is protective against stroke and is safe in long-term follow-up. METHODS: Eleven patients (age 72 +/- 9 years) enrolled in the PLAATO feasibility and safety trial at our institution were followed (36 +/- 1.4) months. All patients had contraindications to anticoagulation and had at least one risk factor for stroke. The predicted stroke risk for this cohort was 8.6% per year as calculated using the CHADS2 score (A validated scoring system assigning 1 point for CHF, hypertension, diabetes, and age >75 years, and 2 points for history of stroke). The primary end-point was the incidence of stroke, and secondary end points were complications related to PLAATO device and systemic embolic events. RESULTS: There was one stroke during follow-up; the stroke risk in our population was 3% per year. Interestingly, the observed stroke risk in these patients after occluding the left atrial appendage is comparable to what would have been observed with warfarin. No systemic embolic events were noted in our cohort and no long term complications related to PLAATO were seen. CONCLUSION: The PLAATO device decreases the risk of stroke in a high-risk cohort of AF patients. Furthermore, the safety of this device is confirmed during this long-term follow up study. A larger trial is needed to validate these findings. PMID- 17351924 TI - Renal artery aneurysm treatment with coil embolization. AB - Renal artery aneurysm is a rare condition, but its incidence has increased through discovery because of improved imaging techniques. However, a therapeutic approach for renal artery aneurysm has not been established. We report the case of a 58-year-old female who had developed hypertension at 52 years of age and was under oral medication for this condition. In a medical check-up, a right renal artery aneurysm of 10 mm in diameter was detected by computed tomography (CT). Renal function was normal and there were no abnormalities in urinalysis; therefore, the patient was observed as an outpatient. Abdominal CT performed 9 months later revealed a saccular renal artery aneurysm of 15 mm in diameter with partial wall calcification and mild mural thrombus. Selective right renal arteriography detected a tumor with calcification, but no renal arterial stenosis or renal arteriovenous fistula. Since the aneurysm had enlarged, catheter treatment was selected to reduce the risk of rupture. A 6-Fr guide catheter was inserted into the right renal artery and the tip of a microcoil catheter was advanced into the aneurysm, which was then embolized with 12 microcoils. The absence of the aneurysm was confirmed using right renal arteriography. No complications occurred during or after embolization, and selective right renal arteriography performed 3 months later showed no change in the coil position or blood flow in the aneurysm, suggesting a good postoperative course. Our results suggest that this approach may generally be applicable for renal artery aneurysms, depending on the shape, size, and location of the aneurysm. PMID- 17351926 TI - New respect for old conditions. PMID- 17351927 TI - Physician-diagnosed asthma and acute chest syndrome: associations with NOS polymorphisms. AB - The main objectives of this paper were to test the hypothesis that polymorphisms in NOS1 and NOS3 genes associate with ACS in SCD patients and to characterize the association between physician-diagnosed asthma and acute chest syndrome (ACS). Case-control study of sickle cell disease patients >or=5 years old with ACS (cases; n=86) and those without ACS (controls; n=48) was carried out. Associations between ACS and the AAT repeat in intron 13 (formerly intron 20) of the NOS1, and with NOS3 T-786C polymorphism were explored. Physician-diagnosed asthma was determined by chart review, patient- or parent (guardian)-reported asthma, and drug use. Eighty five percent of participants with asthma had at least one episode of ACS compared to 14.6% of controls: adjusted odds ratio (OR) (95%CI) 5.46 (2.20,13.5), P= or<0.0001. Asthma correlated with the number of episodes of ACS (P<0.001). NOS1 AAT repeat polymorphism associated with the risk of ACS (P=0.001) in patients without physician-diagnosed asthma. No associations were found between the genotype of the NOS3 T-786C SNP and ACS. Physician diagnosed asthma is a major risk factor for ACS. NOS1 AAT repeat polymorphism may contribute to physician-diagnosed asthma. PMID- 17351928 TI - Association between inflammatory markers in induced sputum and clinical characteristics in children with non-cystic fibrosis bronchiectasis. AB - To study clinical, radiological and laboratory features of children with non cystic fibrosis (non-CF) bronchiectasis (BE) and the association between symptom scores, spirometry, high-resolution computed tomography (HRCT) findings and inflammatory markers in induced sputum in these children. Twenty-seven children with steady-state non-CF BE were cross-sectionally evaluated by symptom scores, pulmonary function tests, anatomic extension and severity scores of BE in HRCT and tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) levels in induced sputum. There were 16 girls and 11 boys. Median (interquartile range) age of study group was 11.4 (9.5-13.6) years, follow-up duration was 3.5 (2-6.5) years and symptom scores were 4 (3-6). Pulmonary function tests revealed FEV(1) of 82%pred (72-93), FVC of 82%pred (74-92), and FEF(25-75%) of 82%pred (68-95). According to anatomic extent of BE on HRCT; 2 patients had mild, 4 had moderate and 21 had severe BE. Based on severity scores of HRCT; 10 patients had mild, 10 had moderate and 7 had severe BE. Neutrophils consisted 29.9% (14.9-53.7) of the total leucocytes in induced sputum samples. Sputum concentration of TNF-alpha was 58 pg/ml (9.2-302) while IL-8 concentration was 2.7 ng/ml (1.7-2.8). Symptom scores correlated with FEV(1) and sputum IL-8 levels (r=-0.49, r=0.67, P<0.05). There was a significant correlation between HRCT severity scores and symptoms, FEV(1), sputum IL-8 and TNF-alpha levels (r=0.64, r=-0.68, r=0.41, r=0.41, respectively, P<0.05). In children BE is associated with ongoing inflammation. This inflammation can be reliably monitored by radiological scores, spirometry, as well as sputum inflammatory markers. Follow-up of children with BE using these clinical tools may improve patient care. PMID- 17351929 TI - Hypertrichosis as a side effect of inhaled steroids in children. AB - Three spontaneous reports of patients in whom a relationship between hypertrichosis and inhaled corticosteroids (ICS) was suspected, were reported to Lareb, The Netherlands Pharmacovigilance Center. We sought evidence for and against a causal relationship between hypertrichosis and ICS in children. The relationship between hypertrichosis and ICS was studied mathematically by assessing the Reporting Odds Ratio (ROR) and by determining the Naranjo Score (NS). We also studied the reports sent to the Pharmacovigilance Database of the Uppsala Monitoring Centre (UMC) of the WHO and reviewed the literature. In the Dutch children, the ROR between hypertrichosis and ICS was 14.6 (95%CI 3.6-59.5), the NS was 4. In the database of the UMC 20 more reports on hypertrichosis and ICS were found, contributing to the results of the Dutch database. Taken together, 11 boys and 12 girls were involved with a mean age of 7 years (range 1 17). The time between the start of ICS and the occurrence of hypertrichosis varied between 1 month and 3 years. Besides the hypertrichosis, growth retardation was found in 5 children and adrenal suppression in 12. In 12 children the outcome after cessation was reported: in 6 children the hypertrichosis improved, whilst in 6 it did not. We found sufficient evidence to support the suspicion that hypertrichosis might be a true adverse effect of ICS. We found no simple dose-effect relationship but obviously there is an individual susceptibility. After cessation of ICS the exaggerated hair growth will not disappear in all children. Hypertrichosis may be a useful clinical pointer to exogenous steroid excess. PMID- 17351930 TI - Oral antiplatelet therapy for percutaneous coronary revascularization. AB - Great strides in interventional pharmacotherapy have been made over the past few decades, virtually all focused on optimizing peri-PCI antithrombotic therapy in order to reduce thrombotic complications. Our understanding of the role of platelets and of antiplatelet therapies in this process continues to evolve. Today, dual or even triple antiplatelet therapy has become standard of care at the time of PCI followed by dual therapy long-term in the majority of patients. However, currently available oral regimens are hampered by limitations including the need to initiate treatment at least a few hours before the procedure to achieve maximum benefit and the safety issues surrounding irreversible platelet inhibition in the uncommon, but not rare situations when a patient requires surgical revascularization. These limitations have led to the suboptimal "real world" utilization of these proven agents and have fostered the development of a wide variety of alternative platelet inhibitors with theoretical, but still unproven clinical benefits. There are ample clinical data that strongly support the use of aspirin and clopidogrel in virtually all patients undergoing a PCI today. This review will highlight these data as well as emphasize the gaps in our understanding. (c) 2007 Wiley-Liss, Inc. PMID- 17351931 TI - Predictors of carotid stent restenosis. AB - OBJECTIVES: We sought to determine the predictors of restenosis after carotid artery stenting and report alternatives for its management. BACKGROUND: Carotid artery stenting has been increasingly accepted as an alternative to carotid endarterectomy (CEA). Predictors of carotid stent restenosis have not been firmly established, and management of restenotic lesions can be challenging. METHODS: A retrospective, single-center review was conducted of 399 carotid stent procedures in 363 patients over 9 years, with a mean follow-up of 24 months (range 6-99 months). Clinical variables included age, gender, symptoms, hypertension, diabetes, tobacco use, renal insufficiency, coronary artery disease, hyperlipidemia, peripheral vascular disease, history of CEA, and history of neck radiation (XRT). Angiographic variables included reference vessel diameter, lesion length, post-stenting residual stenosis, stent diameter, type of stent, and number of stents. RESULTS: Overall, restenosis occurred in 15 patients (3.8%). However, the restenosis occurred in 7 of 35 (20%) patients who had previous XRT, 6 of 57 (10.5%) patients who had previous CEA, and 2 of 9 (22%) patients who previously had both CEA and XRT. The only analyzed variables that were significantly associated with an increased risk of restenosis were previous CEA (OR 4.28, P = 0.008) or XRT (OR 11.3, P 0.5 to 2.0, >2.0 to 5.0, and >5.0. Whereas the daily drug dose in mg/kg was significantly higher when the levels were >5.0 microg/mL, there was no consistent relation between dose and level below that threshold. In adult patients getting standard doses of voriconazole orally, the drug levels are highly variable. Based on limited available data, between a quarter and two-thirds of these levels could potentially be associated with a lower likelihood of response or a higher likelihood of failure. CONCLUSIONS: Future voriconazole studies should incorporate prospective therapeutic drug monitoring and consideration should be given to checking levels in patients receiving the drug for confirmed, life threatening fungal infections. PMID- 17351938 TI - Pulmonary manifestations in patients with cutaneous T-cell lymphomas. AB - BACKGROUND: Lungs are among the most common organs of extranodal involvement by cutaneous T-cell lymphomas (CTCLs), yet the magnitude of lung involvement is not clear, and only a few case reports have addressed this issue to date. The objective of this study was to present the authors' observations on how to recognize lung involvement by CTCL and evaluate the clinical and radiologic differences between involvement of the lungs by CTCL and by pneumonia. METHODS: A retrospective analysis was conducted of all 710 patients with confirmed CTCL who presented to The University of Texas M. D. Anderson Cancer Center between January 1996 and January 2005. Demographics, tumor characteristics, respiratory symptoms, thoracic imaging, microbiology, and laboratory studies were reviewed. RESULTS: During the 9-year period that was studied, 122 patients presented with pulmonary radiologic abnormalities, including 67 patients who also had respiratory symptoms. Pneumonia (n = 27 patients) or lung involvement (n = 6 patients) in patients with CTCL were associated with high mortality rates (hazard ratio, 1.82; 95% confidence interval, 1.08-3.07%; P = .026). The pathogens that were isolated from lower respiratory cultures were Staphylococcus aureus (n = 4 patients), Aspergillus fumigatus (n = 2 patients), Mycobacterium avium-intracellulare (n = 2 patients), Pseudomonas aeruginosa (n = 1 patient), respiratory syncytial virus (n = 1 patient), and Candida parapsilosis (n = 1 patient). Most of the radiologic findings in patients with pneumonia were opacities. Six patients had involvement of lung by CTCL, and most common radiologic pulmonary findings were either a solitary nodule or multiple progressing pulmonary nodules. CONCLUSIONS: Pneumonia and lung involvement by CTCL are relatively rare but portend poor survival. Thus, patients with CTCL should be evaluated thoroughly with thoracic imaging when they experience respiratory symptoms. PMID- 17351939 TI - Intracytoplasmic lumina in metastatic medullary thyroid carcinoma. PMID- 17351940 TI - Immunocytochemistry for hepatocyte nuclear factor-1beta (HNF-1beta): a marker for ovarian clear cell carcinoma. AB - Recent microarray studies have shown that the expression of hepatocyte nuclear factor-1beta (HNF-1beta) was significantly up-regulated in clear cell carcinoma (CCC) of the ovary. HNF-1beta may be a useful marker for CCC in peritoneal fluid cytology. We designed an experimental study using three CCC cell lines to evaluate the influence of alcohol fixation or air drying on immunocytochemistry for HNF-1beta. Each cell line was cultured on chamber slides or transplanted into the abdominal cavity of nude mice, then the slides or ascites smears of nude mice were immunostained with or without microwave-mediated epitope retrieval. Immunoreactivity with HNF-1beta, which was either alcohol-fixed or air-dried, was noticeably improved after microwave heating. In contrast, two serous adenocarcinoma cell lines never showed immunoreactivity. Based on these results, 21 archival Papanicolaou-stained slides of peritoneal fluid (5 CCCs, 12 serous, 2 mucinous, and 2 endometrioid adenocarcinomas) were decolorized and immunostained under heating pretreatment. Five of 5 CCCs were distinctively positive for HNF 1beta, whereas all non-CCC ovarian cancers were negative for this protein. The present study clearly demonstrated that heating epitope retrieval improved the immunoreactivity for a nuclear protein in alcohol-fixed or air-dried cytology specimens. HNF-1beta is likely to be helpful for the diagnosis of CCC in the peritoneal fluid. PMID- 17351941 TI - Needle aspiration cytology and immunohistologic findings in a case of leiomyosarcoma of the breast. PMID- 17351942 TI - Primary pleural epithelioid hemangioendothelioma with rhabdoid phenotype: report and review of the literature. AB - Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor described in diverse locations including lung and liver. Relative to these sites, primary EHE of the serous cavities is uncommon. EHE in the serous cavities mimics mesothelioma and adenocarcinoma clinically, radiographically, cytologically, and histologically. EHEs have plasmacytoid epithelioid cells with cytoplasmic vacuoles. In addition to these features, we noted eccentric nuclei with abundant eosinophilic cytoplasm and nuclei displaced peripherally by globular cytoplasmic inclusions imparting a "rhabdoid" phenotype. These cells were often seen surrounding a hyaline core. Rhabdoid features are not unique to a single entity, and a comprehensive immunohistochemical panel is essential. We report the occurrence of pleural EHE with rhabdoid features presenting in a pleural effusion, and review the literature of primary serosal EHEs. PMID- 17351943 TI - Endocervical component in conventional cervical smears: influence on detection of squamous cytologic abnormalities. AB - The objective of this study was to correlate the number of endocervical cells and the number of atypical cells in cervical smears with cytological abnormalities to verify if a higher number of endocervical cells would implicate in a higher number of squamous atypical cells. In this cross sectional study, it was made a blinded review of 294 conventional cervical smears. The consensus diagnoses reached by the blinded review by three observers included 213 low-grade squamous intraepithelial lesions (LSILs) and 81 high-grade squamous intraepithelial lesions (HSILs). In each cervical smear were computed the number of endocervical cells and the number of squamous atypical cells, and it was established the following score: one (0-5 cells); two (6-10 cells); three (11-25 cells); four (26 50 cells); and five (more than 50 cells). Compared to the smears with an account of endocervical cells classified in score 1 (0-5 cells), an account of more than 50 endocervical cells was significantly associated to the presence of at least 10 squamous atypical cells in the cervical smears (OR 2.87 95% CI 1.54-5.35). Data from this study suggest that there is a positive association between the number of endocervical cells and the number of squamous atypical cells suggestive of SIL. PMID- 17351944 TI - Molecular diagnostic testing as an adjunct to morphologic evaluation of pancreatic ductal system brushings: potential augmentation for diagnostic sensitivity. AB - Malignancies arising from the pancreatic and biliary ductal systems present the gastroenterologist and pathologist with diagnostic challenges. Tumors of the pancreatic and/or biliary ductal system may present as either duct strictures or mass lesions. When lesions present as strictures without associated demonstrable masses, brushing cytology may represent the only reasonable diagnostic technique aside from open biopsy. Diagnostic sensitivities for brushing cytology have ranged from 18 to 90%. Positive diagnoses of malignancy are of great clinical value but a negative result is of relatively little clinical aid when the radiographic or clinical findings are suspicious for a malignancy.A variety of techniques have been used in an attempt to improve diagnostic sensitivity for brushing cytology. These have included immunohistochemistry and various molecular diagnostic techniques. Using the high resolution melting curve technique, we performed mutational analysis on 20 bile duct brushing specimens for mutations in p53, K-ras, BRAF, and EGFR genes. Eleven specimens had corresponding surgical specimens, which were similarly analyzed. Our series included twelve adenocarcinomas, one islet cell tumor, one case of dysplasia, and six benign cases. K-ras mutations were found in cytology specimens of 3 out of 12 malignancies. No EGFR or B-raf mutations were detected and only a single p53 mutation in an adenocarcinoma was detected in the corresponding cytology specimen. No mutations were detected in benign lesions or in the dysplasia. Only 8% of specimens from adenocarcinomas had p53 mutations and only 33% of cases had K-ras mutations. Mutational analysis did not appear to improve the cytologic detection of adenocarcinoma by bile duct brushings. PMID- 17351945 TI - Metastatic thymic carcinoma with hyaline stromal material mimicking adenoid cystic carcinoma. PMID- 17351946 TI - Mucinous carcinoma of breast with abundant psammoma bodies in fine-needle aspiration cytology: a case report. AB - Fine-needle aspiration (FNA) cytology plays an important role in the diagnosis of various pathologic conditions in the breast. Microcalcification can be observed in benign and malignant breast lesions, but psammoma bodies (PBs) are rarely reported in breast lesions and are a feature of papillary neoplasms. However, we have observed PBs in large numbers in a mucinous carcinoma of breast, which is not previously reported in FNA of breast lesions. A 65-yr-old postmenopausal woman underwent FNA of a palpable mass. The aspirate revealed mucinous carcinoma cells associated with plenty of PBs. This case report of mucinous carcinoma of the breast with abundant PBs highlights the cytodiagnostic pattern of the lesion and formation of PBs. PMID- 17351947 TI - Solitary fibrous tumor of the lung: a case report with a study of the aspiration biopsy, histopathology, immunohistochemistry, and autopsy findings. AB - Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm of ubiquitous location. In addition to its classic presentation as a pleural-based mass, it can be encountered in a variety of other sites. A pleural-based lung lesion can be easily accessed by radiologic guidance for cytologic study. Several reports have described the cytologic findings of SFT at various locations, including the lung. However, diagnostic difficulties can occur due to unusual clinical, radiologic, atypical cytomorphologic, and histologic features. We describe a case of intrapulmonary SFT in which a false-positive malignant diagnosis was rendered on fine-needle aspiration biopsy and concurrent surgical core biopsy prior to radiofrequency ablation. The patient died of procedural complications, and an autopsy was performed. Retrospective study of the case, especially correlation of cytologic, histologic, autopsy findings, and immunohistochemistry results were helpful in correctly diagnosing the case as SFT. We are reporting this case with emphasis on avoiding diagnostic pitfalls by being familiar with the accepted cytohistologic features and appropriate immunohistochemical results. PMID- 17351948 TI - Ciliated hepatic foregut cyst: report of a case on fine-needle aspiration. AB - Ciliated hepatic foregut cyst (CHFC) is a rare, benign, solitary cyst consisting of ciliated columnar epithelium. They are lined by a layer of ciliated columnar cells and contain mucoid material and debris. It is the ciliated epithelium that distinguishes them from other hepatic cysts. The cyst is generally found incidentally on radiologic imaging or during surgical exploration. There has been an increase in the number of reports of CHFC during the past 15 years in the surgical pathology literature, presumably because of increased availability of various radiologic imaging modalities. Although it is rare, CHFC should be included in the differential diagnosis of cystic lesions of the liver and is important to consider in aspirates obtained for the evaluation of possible neoplastic disease. We report a case diagnosed by fine-needle aspiration for a liver cyst discovered incidentally during the evaluation of acute pancreatitis. PMID- 17351949 TI - Telangiectatic osteosarcoma: the St. Jude Children's Research Hospital's experience. AB - BACKGROUND: Telangiectatic osteosarcoma (TOS) is a rare subtype of osteosarcoma (OS). The authors reviewed their experience with TOS to characterize its histologic, radiologic, and clinical features. METHODS: The authors reviewed records, pathology material, and imaging studies from all patients with TOS who were treated between 1978 and 2005 and compared their outcomes with the outcomes of patients with all other subtypes of high-grade osteosarcoma (OS). RESULTS: Among 323 patients with OS, 22 patients (6.8%) had TOS. Two additional patients who were treated in Chile on a recent OS trial were included. The median age at diagnosis of the 24 patients was 15.7 years. Four patients (17%) had metastatic disease, and 9 of 21 patients (43%) had pathologic fractures. Only 5 patients (who were treated after 1994) underwent limb-salvage surgery. Estimates of 5-year event-free survival (58.3% +/- 11.9%) and overall survival (66.8% +/- 11.6%) were similar to those for patients with other OS subtypes (P > or = .85). The absence of local disease progression and chemotherapy with > or =3 agents that were active against OS were correlated with improved outcome (P < or = .005). The presence of a pathologic fracture was not associated with surgery type or patient outcome. CONCLUSIONS: TOS was associated with a high rate of pathologic fracture. With multimodality therapy, the outcome of patients with TOS was similar to that of patients with other high-grade OS subtypes. The absence of local disease progression and chemotherapy with > or =3 active agents were associated with a favorable outcome. PMID- 17351950 TI - Phase II randomized study of daily gefitinib treatment alone or with vinorelbine every 2 weeks in patients with adenocarcinoma of the lung who failed at least 2 regimens of chemotherapy. AB - BACKGROUND: The objective of this study was to assess the efficacy of adding chronic, intermittent, low-dose vinorelbine to gefitinib treatment for patients who had adenocarcinoma of the lung who failed>or=2 regimens of chemotherapy. METHODS: Patients were randomized into 2 arms: Oral gefitinib 250 mg daily (the G arm) or vinorelbine 15 mg/m2 as an intravenous infusion on Day 1 and oral gefitinib 250 mg daily on Days 2 through 14 every 2 weeks (the GV arm). From August 2004 to October 2005, 48 patients were enrolled. Epidermal growth factor receptor (EGFR) exon 18 through 21 nucleotide sequence analysis and fluorescence in situ hybridization were performed in patients who had tumor tissue specimens available for analysis. RESULTS: After randomization, each arm had 24 patients. However, 3 patients refused vinorelbine treatment and were given gefitinib treatment only. Thus, 27 patients received G treatment, and 21 patients received GV treatment. Objective response rates were 55.6% in the G arm and 52.4% in the GV arm. All toxicities in both arms were mild. The 1-year progression-free survival rate was 57.1% in the GV arm and 21.2% in the G arm (P=.008). The median survival was 13.3 months in the G arm and 23.4 months in the GV arm (P=.1231). Three of 6 patients (50%) had an exon 19 in-frame deletion, and 2 of 10 patients had EGFR gene high polysomy or amplification (20%). CONCLUSIONS: Gefitinib was highly effective in ethnic Chinese patients with adenocarcinoma of the lung who failed previous platinum and taxane treatment. The addition of low-dose vinorelbine every 2 weeks produced a significantly better 1-year progression-free survival rate. PMID- 17351951 TI - Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study. AB - BACKGROUND: It is believed widely that chemotherapy-induced cognitive impairment occurs in a subgroup of patients with breast cancer. However, recent reports have provided no evidence that chemotherapy affects cognition. In this study, the authors questioned whether cognitive compromise in patients with breast cancer is attributable to chemotherapy. In addition, the effects of therapy-induced menopause and of the erythropoiesis-stimulating factor darbepoetin alpha on cognitive performance were assessed. METHODS: A battery of neuropsychological tests was used to assess cognitive performance in 101 patients with breast cancer before neoadjuvant chemotherapy (T1) and toward the end of neoadjuvant chemotherapy (T2) with combined epirubicin, paclitaxel, and cyclophosphamide with concomitant darbepoetin alpha. Repeated-measures multiple analyses of variance and a reliable-change approach were used for statistical analyses. RESULTS: At T1, the group means ranged below the test norms in 5 of 12 cognitive tests. At T2, multiple analyses of variance (MANOVA) indicated a significant overall improvement in the test results (P<.001). After correcting for practice effects, cognitive decline predominated in 27% of patients, whereas improvement predominated in 28% of patients. Cognitive performance was not related significantly to self-reported cognitive problems, anxiety and depression, menopause, or darbepoetin alpha administration. CONCLUSIONS: Even before chemotherapy, a subgroup of patients with breast cancer showed cognitive compromise that was unrelated to anxiety or depression. During chemotherapy, cognitive function remained stable in most patients, improved in a subgroup, and deteriorated in another subgroup. The deterioration may have been caused by side effects of chemotherapy, but it also may have been related to currently unidentified factors that cause prechemotherapy cognitive compromise. Therapy induced menopause and darbepoetin alpha did not appear to influence cognition. PMID- 17351952 TI - Prophylactic salpingo-oophorectomy in a series of 89 women carrying a BRCA1 or a BRCA2 mutation. AB - BACKGROUND: Prophylactic salpingo-oophorectomy (SO), which is recommended in BRCA1/2 mutation carriers, still needs to be reappraised. METHODS: In all, 89 BRCA1/BRCA2 mutation carriers underwent SO between 1994-2004. Past medical and familial history, SO, results and survival after SO were analyzed. RESULTS: The series consisted of 56 BRCA1 and 33 BRCA2 mutation carriers. All but 1 had a family history of breast (BC) and/or ovarian cancer; 42 BRCA1 and 31 BRCA2 had a personal history of BC. The median age at SO was 44 (BRCA1) and 49.5 (BRCA2) years for women without previous BC (not significant) and 48 (BRCA1) and 53 BRCA2) years (P=.03) for women with previous BC. Occult ovarian (n=2) and/or fallopian (n=3) carcinomas were found in 4 patients (4.5%): 1 experienced recurrence (4 years), 2 are disease-free (26 and 38 months of follow-up), and 1 died from BC (12 months). Among the other 69 patients with previous BC (median follow-up, 42 months), 14 developed ipsilateral or contralateral BC and 8 developed metastatic disease. Among the 16 patients without previous BC (median follow-up, 27 months), 3 developed BC. Of the 89 patients, 85 are still alive: 3 died from BC and 1 died from pancreatic cancer. No peritoneal malignancy was observed. CONCLUSIONS: This study shows that prophylactic SO remains an important option for BRCA1/2 mutation carriers as asymptomatic ovarian/fallopian cancers were found in 4.5% of patients. However, a longer follow-up and larger series are required to more precisely evaluate the benefits of this procedure in terms of BC incidence, peritoneal malignancy, or recurrence. PMID- 17351953 TI - Multimodality treatment of melanoma brain metastases incorporating stereotactic radiosurgery (SRS). AB - BACKGROUND: Brain metastases are a frequent complication in advanced melanoma. A 3.6 to 4.1-month median survival has been reported after treatment with whole brain radiotherapy. We performed a retrospective analysis of our institutional experience of multimodality treatment utilizing linear accelerator (Linac)-based stereotactic radiosurgery (SRS). METHODS: Forty-four melanoma patients with brain metastases underwent 66 SRS treatments for 156 metastatic foci between 1999 and 2004. Patients were treated with initial SRS if or=70, but 37 patients had active systemic metastases (Recursive Partition Analysis Class 2). Survival was calculated from the time of diagnosis of brain metastases. Minimum follow-up was 1 year after SRS. The potential role of prognostic factors on survival was evaluated including age, sex, interval from initial diagnosis to brain metastases, surgical resection, addition of whole brain radiotherapy (WBRT), number of initial metastases treated, and number of SRS treatments using Cox univariate analysis. RESULTS: The median survival of melanoma patients with brain metastases was 11.1 months (95% confidence interval [CI]: 8.2-14.9 months) from diagnosis. One-year and 2-year survivals were 47.7% and 17.7%, respectively. There was no apparent effect of age or sex. Surgery or multiple stereotactic radiotherapy treatments were associated with prolonged survival. Addition of WBRT to maintain control of brain metastases in a subset of patients did not improve survival. CONCLUSIONS: Our results suggest that aggressive treatment of patients with up to 5 melanoma brain metastases including SRS appears to prolong survival. Subsequent chemotherapy or immunotherapy after SRS may have contributed to the observed outcome. PMID- 17351954 TI - Five-year survival after surgical treatment for kidney cancer: a population-based competing risk analysis. AB - BACKGROUND: Kidney cancer's rising incidence is largely attributable to the increased detection of small renal masses. Although surgery rates have paralleled this incidence trend, mortality continues to rise, calling into question the necessity of surgery for all patients with renal masses. Using a population-based cohort, a competing risk analysis was performed to estimate patient survival after surgery for kidney cancer, as a function of patient age and tumor size at diagnosis. METHODS: With data from the Surveillance, Epidemiology, and End Results Program (1983-2002), a cohort was assembled of 26,618 patients with surgically treated, local-regional kidney cancer. Patients were sorted into 20 age-tumor size categories and the numbers of patients that were alive, dead from kidney cancer, and dead from other causes were tabulated. Poisson regression models were fitted to obtain estimates of cancer-specific and competing-cause mortality. RESULTS: Age-specific kidney cancer mortality was stable across all size strata but varied inversely with tumor size. Patients with the smallest tumors enjoyed the lowest cancer-specific mortality (5% for massesor=70 years) was 28.2% (95% confidence interval [CI]: 25.9%-30.8%), irrespective of tumor size. CONCLUSIONS: Despite surgical therapy, competing-cause mortality for patients with renal masses rises with increasing patient age. After 5 years, one-third of elderly patients (>or=70 years) will die from other causes, suggesting the need for prospective studies to evaluate the role of active surveillance as an initial therapeutic approach for some small renal masses. PMID- 17351955 TI - Predicting blood pressure improvement in hypertensive patients after renal artery stent placement: renal fractional flow reserve. AB - BACKGROUND: Renal stent placement improves or cures hypertension in only 60-70% of patients with renal artery stenosis (RAS) and uncontrolled hypertension. There is a need to better identify patients who are likely to respond to percutaneous renal revascularization. We investigated whether an abnormal renal fractional flow reserve (FFR) would predict blood pressure improvement in patients undergoing renal artery stent placement. METHODS: We prospectively enrolled 17 patients with unilateral RAS and medically refractory hypertension (BP > 140/90 mm Hg). Renal FFR was measured at maximal hyperemia induced by papaverine followed by renal stent placement. Blood pressure improvement was defined as a blood pressure of or =4 sessions were evaluated as the intervention group, and 41 patients who participated in < or =2 sessions comprised the participant group. Hospital Anxiety and Depression Scale (HADS) and the Brief Fatigue Inventory (BFI) were completed before every session, relating to the previous week. RESULTS: BFI scores were higher in the participant group (p=0.06). In the intervention group, the median HADS score for depression was 9 at the beginning and 7 after the fourth appointment (p=0.021). The median BFI score changed from 5.7 to 4.1 (p=0.24). The anxiety score was in the normal range from the beginning. CONCLUSION: Anthroposophical art therapy is worthy of further study in the treatment of cancer patients with depression or fatigue during chemotherapy treatment. PMID- 17351988 TI - Structures, stabilities, and electronic and optical properties of c(58) fullerene isomers, ions, and metallofullerenes. AB - The 1205 classical isomers of fullerene C58, as well as one quasi-fullerene C58 isomer with a heptagonal ring (labeled as Cs:hept) have been investigated by the quantum chemical methods PM3, HCTH/3-21G, and B3LYP/6-31G(d). Isomer C3v:0001, which has the lowest number of adjacent pentagons, is predicted to be the most stable isomer, but the quasi-fullerene isomer Cs:hept is only 2.50 kcal mol-1 higher in energy. Systematic investigations of the electronic properties of C3v:0001 and Cs:hept find that the C3v:0001 isomer has high vertical electron affinity (3.19 eV). The nucleus-independent chemical shifts (NICS) value at the center of Cs:hept (-5.1 ppm) is more negative than that of C60 (-2.8 ppm). The NICS value at the center of the heptagonal ring in Cs:hept (-2.5 ppm) indicates weakly aromatic character. In contrast, the C58(6-) and C58(8-) ions of the C3v:0001 and Cs:hept geometries possess large aromatic character, with NICS values between -14.0 and -26.2 ppm. To clarify the thermodynamic stabilities of C58 isomers at different temperatures, the entropy contributions are taken into account on the basis of the Gibbs energy at the B3LYP/6-31G(d) level. The C3v:0001 isomer prevails in a wide range of temperatures, and the Cs:hept isomer is also an important component around 2800 K. The IR spectra of C58 isomers are simulated to facilitate experimental identification of different isomers. In addition, the electronic spectra and the second-order hyperpolarizabilities are predicted by ZINDO and the sum-over-states model. The static second-order hyperpolarizability of the C3v:0001 isomer is 96.5 % larger than that of C60, and its second-order hyperpolarizabilities at external field frequencies are at least nine times larger than those of C60. PMID- 17351989 TI - Tunable film degradation and sustained release of plasmid DNA from cleavable polycation/plasmid DNA multilayers under reductive conditions. AB - The controllable and sustained release of DNA from the surfaces of biomaterials or biomedical devices represents a new method for localized gene delivery. We report the synthesis of a novel polycation containing disulfide bonds in its backbone and the fabrication of polycation/plasmid DNA multilayered thin films by layer-by-layer assembly. The films are very stable during preparation and in storage, however, they gradually degrade and release the incorporated DNA when incubated in PBS buffer containing dithiothreitol (DTT), which results from the degradation of a disulfide-contained polymer under reductive conditions. The film degradation rate and DNA release rate can be tuned by the concentration of reducing agent. This approach will be useful in gene therapy and tissue engineering by controlled administration of therapeutic DNA deposited on the surface of implantable biomedical devices or tissue engineering scaffolds. PMID- 17351990 TI - Novel dome-shaped structures for high-efficiency patterning of individual microbeads in a microfluidic device. PMID- 17351991 TI - Nanocrystal-based luminescent composites for nanoimprinting lithography. PMID- 17351992 TI - Nanoscale pits as templates for building a molecular device. PMID- 17351993 TI - Porous liquids. AB - The aim of this article is to put forward the novel concept of porous liquids, or, more precisely, liquids with permanent microporosity. In contrast to the small, transient cavities that exist between the molecules of any liquid (here called "extrinsic" porosity), we suggest that a truly microporous liquid could exist if it had empty pores within the molecules of the liquid ("intrinsic" porosity). By using rigid host molecules with restricted access windows, any unwanted occupation of the pores could be prevented (i.e., the pores could be kept empty and available so that the liquid would be genuinely microporous). The liquid could have permanent, well-defined, empty pores capable of molecular recognition when exposed to other species (e.g., gases etc.). We stress that these phases are not the same as simple solutions of host species, in which any pores would normally be occupied by solvent molecules. In microporous liquids, any solvent molecules, if present, would be deliberately sterically excluded from the host cavities, to leave them readily accessible. Microporous liquids would be of considerable fundamental interest. They could combine properties of microporous solids, such as size- and shape-selective sorption and so forth, with the rapid mass transfer, fluidity and fast kinetics of liquids. Some synthetic approaches to these materials are discussed in this article. Also, whilst the overall concept of microporous liquids is new, literature is described which suggests that some examples have arguably already been reported, even if they have not previously been recognised and characterised in such terms. PMID- 17351994 TI - A cell-permeable synthetic transcription factor mimic. PMID- 17351995 TI - Reversible formation of a [2]catenane through first- and second-sphere coordination. PMID- 17351996 TI - A cubic 3d-4f structure with only ferromagnetic Gd-Mn interactions. PMID- 17351997 TI - Palladium-catalyzed coupling of ammonia and hydroxide with aryl halides: the direct synthesis of primary anilines and phenols. PMID- 17351998 TI - An isolable and monomeric phosphorus radical that is resonance-stabilized by the vanadium(IV/V) redox couple. PMID- 17351999 TI - Doping golden buckyballs:Cu@Au16- and Cu@Au17- cluster anions. PMID- 17352000 TI - Iridium-catalyzed synthesis of primary allylic amines from allylic alcohols: sulfamic acid as ammonia equivalent. PMID- 17352001 TI - Charge-metal interaction of a carbon nanotube. PMID- 17352002 TI - Spin-orbit ab initio investigation of the ultraviolet photolysis of diiodomethane. AB - The UV photodissociation (<5 eV) of diiodomethane (CH(2)I(2)) is investigated by spin-orbit ab initio calculations. The experimentally observed photodissociation channels in the gas and condensed phases are clearly assigned by multi-state second-order multiconfigurational perturbation theory in conjunction with spin orbit interaction through complete active space-state interaction potential energy curves. The calculated results indicate that the fast dissociations of the first two singlet states of CH(2)I(2) and CH(2)I--I lead to geminate-radical products, CH(2)I (.)+I((2)P(3/2)) or CH(2)I (.)+ I*((2)P(1/2)). The recombination process from CH(2)I--I to CH(2)I(2) is explained by an isomerization process and a secondary photodissociation reaction of CH(2)I--I. Finally, the study reveals that spin-orbits effects are significant in the quantitative analysis of the electronic spectrum of the CH(2)I--I species. PMID- 17352003 TI - Optical Fourier transform spectroscopy of single-walled carbon nanotubes and single molecules. AB - We use two-beam interferometry in combination with confocal microscopy for Raman and fluorescence studies of spatially isolated single-walled carbon nanotubes and single dye molecules. We investigate the potential of optical Fourier transform spectroscopy for the spectral characterization of single molecules and molecular nanostructures. We demonstrate that it is possible to obtain the temporal coherence characteristics as well as reliable spectroscopic data of the single photon fluorescence emission of an isolated molecule from one measured interferogram, even though the molecule exhibits intensity fluctuations and spectral jumps. PMID- 17352004 TI - Nonlinear optical properties of ferrocene- and porphyrin-[60]fullerene dyads. AB - A series of novel [60]fullerene-ferrocene and [60]fullerene-porphyrin dyads, in which a fullerene and an electron donating moiety are attached through a flexible triethylene glycol linker are synthesized and their nonlinear optical (NLO) response studied. Specifically, the third-order susceptibility chi(3) of all fullerene derivatives are measured in toluene solutions by the optical Kerr effect (OKE) technique using 532 nm, 35 ps laser pulses and their second hyperpolarizability gamma are determined. All fullerene dyads studied exhibit enhancement of their NLO response compared to pristine fullerenes which has been attributed to the formation of a charge separated state. All experimentally measured hyperpolarizability gamma values are also calculated by the semiempirical methods AM1 and PM3. A good correlation is found between the theoretical and experimental values, suggesting that simple semiempirical methods can be employed for the designing and optimization of the fullerene-containing dyads displaying improved nonlinear responses. PMID- 17352005 TI - What is the ideal support group? Views of Australian people with cancer and their carers. AB - AIMS: To explore views on the ideal structure and process of support groups for cancer patients. PATIENTS AND METHODS: From 184 cancer support groups identified in NSW, Australia, 50 were randomly selected within strata of five variations in group structure: homogenous versus heterogenous participants; urban versus rural; community versus hospital setting, leader with cancer experience or not; and with professional training or not. Four hundred and seventy-six group members completed a questionnaire. RESULTS: Participants valued being with others like them, gaining information about cancer and having an effective leader. Groups were seen to be currently failing people from culturally and linguistically diverse backgrounds, and links with oncology health professionals were inadequate. Few clear preferences for structure were expressed, except for the non-exclusion of those with a poor prognosis. Patients tended to prefer the structure of their own group, but patients longer since diagnosis, those with better informal support and carers preferred to meet in the community setting, while men with prostate cancer preferred a medical setting. CONCLUSIONS: Some suggestions for group structure and process can be made on the basis of these findings; however, individual variation suggests that a needs analysis should be made by individual groups. PMID- 17352006 TI - How to provide insomnia interventions to people with cancer: insights from patients. AB - Chronic insomnia affects approximately one quarter of cancer patients. Non pharmacologic interventions are the treatment of choice for chronic insomnia, yet they are rarely offered to people with cancer. The study question was how to make these interventions available to cancer patients. Twenty-six cancer patients who had sleep difficulty participated in focus groups or one-to-one interviews. The key questions included: What would be the best way for you to find out about a service for insomnia treatment? What would make it easy/difficult for you to participate? Transcripts were examined independently by three readers who identified participants' answers to the questions, as well as themes that emerged from participants' reflections on their experience with cancer and sleep difficulty. The readers then worked together to reach consensus on a final classification system for describing the content of patients' responses. Participants provided many practical answers to our specific questions. In addition, the following themes emerged: sleep difficulty needs greater recognition by health professionals; patients wish to receive more information about sleep and sleep difficulty; and that although patients perceive sleep as being important, they are reluctant to report sleep problems to doctors. Furthermore, participants recommended that the assessment and treatment of sleep difficulty be integrated into the health care system while considering the cancer treatment status and energy level of patients. PMID- 17352007 TI - Between traditional and modern perceptions of breast and cervical cancer screenings: a qualitative study of Arab women in Israel. AB - Arab women have undergone major modernization processes in recent years and the effect of these processes on attitudes to screening should be examined. Fifty-one Israeli Arab women participated in focus groups in five representative communities. The women expressed a combination of traditional beliefs and modern biomedical knowledge concerning risk and preventive factors related to cancer. Special importance was given to birth and breast-feeding as protective factors, integrating modern views with traditional concepts of motherhood as a woman's principal role in society. A major theme on who or what was responsible for one's health emerged, opinions ranging across fate and God's will, physicians and health services, or, as a substantial number of participants asserted, taking personal responsibility for one's health. A related theme that emerged was the perception of cancer as either a punishment or as a test devised by God. Fears of stigma related to breast or gynecological examinations, worries about the spouse's reaction once a lump is detected, and worries regarding the violation of religious and cultural requirements of modesty, were expressed. However, there was firm agreement that although these created emotional difficulties, they were not sufficiently important to cause women to forgo screenings. PMID- 17352008 TI - The hepatic sinusoidal endothelial lining and colorectal liver metastases. AB - Colorectal cancer (CRC) is a common malignant disease and the severe nature of cases in men and women who develop colorectal cancer makes this an important socio-economic health issue. Major challenges such as understanding and modeling colorectal cancer pathways rely on our understanding of simple models such as outlined in this paper. We discuss that the development of novel standardized approaches of multidimensional (correlative) biomolecular microscopy methods facilitates the collection of (sub) cellular tissue information in the early onset of colorectal liver metastasis and that this approach will be crucial in designing new effective strategies for CRC treatment. The application of X-ray micro-computed tomography and its potential in correlative imaging of the liver vasculature will be discussed. PMID- 17352009 TI - Current role of bloodless liver resection. AB - Liver resections are demanding operations which can have life threatening complications although they are performed by experienced liver surgeons. Recently new technologies are applied in the field of liver surgery, having one goal: safer and easier liver operations. The aim of this article is to address the issue of bloodless liver resection using radiofrequency energy. Radionics, Cool tip System and Tissue Link are some of the devices which are using radiofrequency energy. All information included in this article, refers to these devices in which we have personal experience in our unit of liver surgery. These devices take advantage of its unique combination of radiofrequency current and internal electrode cooling to perform sealing of the small vessels and biliary radicals. Dissection is also feasible with the cool-tip probe. For the purposes of this study patient sex, age, type of disease and type of surgical procedure in association with the duration of parenchymal transection, blood loss, length of hospital stay, morbidity and mortality were analyzed. Cool-tip RF device may provide a unique, simple and rather safe method of bloodless liver resections if used properly. It is indicated mostly in cirrhotic patients with challenging hepatectomies (segment VIII, central resections). The total operative time is eliminated and the average blood loss is significantly decreased. It is important to note that this technique should not be applied near the hilum or the vena cava to avoid damage of these structures. PMID- 17352011 TI - Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis. AB - AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n=45), borderline NASH (n=24), simple fatty liver (n=9), and normal tissue (n=5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA. RESULTS: Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively. CONCLUSION: Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology. PMID- 17352010 TI - Novel approaches towards conquering hepatitis B virus infection. AB - Currently approved treatments for hepatitis B virus (HBV) infection include the immunomodulatory agent, IFN-alpha, and nucleos(t)ide analogues. Their efficacy is limited by their side effects, as well as the induction of viral mutations that render them less potent. It is thus necessary to develop drugs that target additional viral antigens. Chemicals and biomaterials by unique methods of preventing HBV replication are currently being developed, including novel nucleosides and newly synthesized compounds such as capsid assembling and mRNA transcription inhibitors. Molecular therapies that target different stages of the HBV life cycle will aid current methods to manage chronic hepatitis B (CHB) infection. The use of immunomodulators and gene therapy are also under consideration. This report summarizes the most recent treatment possibilities for CHB infection. Emerging therapies and their potential mechanisms, efficacy, and pitfalls are discussed. PMID- 17352012 TI - Adherence and invasion of mouse-adapted H pylori in different epithelial cell lines. AB - AIM: To assess the adhesion and invasion abilities of different mouse adapted H pylori strains in different cell lines in vitro and investigate their effects on the virulence factors cagA and vacA. METHODS: The adherence and invasion abilities of different H pylori strains in different epithelial cell lines were examined by the gentamycin protection assay. The null mutants of cagA and vacA were processed by direct PCR mutation method. The morphologic changes of different cell lines after H pylori attachment were examined by microscopy. RESULTS: The densities of adherence to and invasion into cells in vitro were different from those in the mouse infection experiments. 88-3887 strain could invade and adhere to cells stronger than SS1 and X47. All tested strains had better adhering and invasive abilities in SCG-7901 cell. CagA and vacA minus mutants had the same invasion and adherent abilities as their wild types. In all strains and cell lines tested, only AGS cell had the significant hummingbird phenotype after inoculation with the 88-3887 wild-type. CONCLUSION: Both the host cells and the bacteria play important parts in the invasion and adhesion abilities of H pylori. CagA and VacA are not related to the ability of invasion and adhesion of H pylori in different cell lines in vitro. PMID- 17352013 TI - Proteasome inhibition-induces endoplasmic reticulum dysfunction and cell death of human cholangiocarcinoma cells. AB - AIM: To determine if proteasome inhibition induces apoptosis in human cholangiocarcinoma cells, and if so, to elucidate the cellular mechanisms. METHODS: Studies were performed in the human KMCH, KMBC, and Mz-ChA-1 cholangiocarcinoma, and normal rat cell lines. MG132, a peptide aldehyde, which inhibits the chymotrypsin-like activity of the proteasome was employed for this study. Apoptosis was assessed morphologically by 4'-6-Diamidino-2-phenylindole (DAPI) nuclear staining and fluorescence microscopy. Mitochondrial membrane potential was examined using a fluorescent unquenching assay. Ultrastructural changes during cell death were examined using transmission electron microscopy (TEM). Caspase 3/7 activity was assessed using an enzymatic-based fluorescent assay. Cytosolic-free calcium concentrations were measured using Fura-2 and digitized fluorescent microscopy. RESULTS: MG132, a proteasome inhibitor, induced apoptosis in all the cholangiocarcinoma cell lines examined. In contrast, minimal cytotoxicity was observed in normal rat cholangiocytes. Apoptosis was time- and concentration-dependent. There was no change in the mitochondrial membrane potential between treated and untreated cells. Ultrastructural examination by transmission electron microscopy displayed the classic features of apoptosis, but in addition, there was also dramatic vacuolization of the endoplasmic reticulum (ER). Unexpectedly, no increase in caspase 3/7 activity was observed in MG132 treated cells, nor did the pancaspase inhibitor, Q-VD-OPh prevent cell death. The protein synthesis inhibitor, cycloheximide, blocked apoptosis induced by proteasome inhibitor indicating that ER dysfunction was dependent upon the formation of new proteins. CONCLUSION: Proteasome inhibition induces ER dysfunction and caspase-independent cell death selectively in human cholangiocarcinoma cells. Proteasome inhibitors warrant evaluation as anticancer agents for the treatment of human cholangiocarcinoma. PMID- 17352014 TI - Pancreatic carcinoma coexisting with chronic pancreatitis versus tumor-forming pancreatitis: diagnostic utility of the time-signal intensity curve from dynamic contrast-enhanced MR imaging. AB - AIM: To evaluate the ability of the time-signal intensity curve (TIC) of the pancreas obtained from dynamic contrast-enhanced magnetic resonance imaging (MRI) for differentiation of focal pancreatic masses, especially pancreatic carcinoma coexisting with chronic pancreatitis and tumor-forming pancreatitis. METHODS: Forty-eight consecutive patients who underwent surgery for a focal pancreatic mass, including pancreatic ductal carcinoma (n=33), tumor-forming pancreatitis (n=8), and islet cell tumor (n=7), were reviewed. Five pancreatic carcinomas coexisted with longstanding chronic pancreatitis. The pancreatic TICs were obtained from the pancreatic mass and the pancreatic parenchyma both proximal and distal to the mass lesion in each patient, prior to surgery, and were classified into 4 types according to the time to a peak: 25 s and 1, 2, and 3 min after the bolus injection of contrast material, namely, type-I, II, III, and IV, respectively, and were then compared to the corresponding histological pancreatic conditions. RESULTS: Pancreatic carcinomas demonstrated type-III (n=13) or IV (n=20) TIC. Tumor-forming pancreatitis showed type-II (n=5) or III (n=3) TIC. All islet cell tumors revealed type-I. The type-IV TIC was only recognized in pancreatic carcinoma, and the TIC of carcinoma always depicted the slowest rise to a peak among the 3 pancreatic TICs measured in each patient, even in patients with chronic pancreatitis. CONCLUSION: Pancreatic TIC from dynamic MRI provides reliable information for distinguishing pancreatic carcinoma from other pancreatic masses, and may enable us to avoid unnecessary pancreatic surgery and delays in making a correct diagnosis of pancreatic carcinoma, especially, in patients with longstanding chronic pancreatitis. PMID- 17352015 TI - Embryonic stem cells develop into hepatocytes after intrasplenic transplantation in CCl4-treated mice. AB - AIM: To transplant undifferentiated embryonic stem (ES) cells into the spleens of carbon tetrachloride (CCl4)-treated mice to determine their ability to differentiate into hepatocytes in the liver. METHODS: CCl4, 0.5 mL/kg body weight, was injected into the peritoneum of C57BL/6 mice twice a week for 5 wk. In group 1 (n=12), 1 x 10(5) undifferentiated ES cells (0.1 mL of 1 x 10(6)/mL solution), genetically labeled with GFP, were transplanted into the spleens 1 d after the second injection. Group 2 mice (n=12) were injected with 0.2 mL of saline twice a week, instead of CCl4, and the same amount of ES cells was transplanted into the spleens. Group 3 mice (n=6) were treated with CCl4 and injected with 0.1 mL of saline into the spleen, instead of ES cells. Histochemical analyses of the livers were performed on post-transplantation d (PD) 10, 20, and 30. RESULTS: Considerable numbers of GFP-immunopositive cells were found in the periportal regions in group 1 mice (CCl4-treated) on PD 10, however, not in those untreated with CCl4 (group 2). The GFP-positive cells were also immunopositive for albumin (ALB), alpha-1 antitrypsin, cytokeratin 18, and hepatocyte nuclear factor 4 alpha on PD 20. Interestingly, most of the GFP positive cells were immunopositive for DLK, a hepatoblast marker, on PD 10. Although very few ES-derived cells were demonstrated immunohistologically in the livers of group 1 mice on PD 30, improvements in liver fibrosis were observed. Unexpectedly, liver tumor formation was not observed in any of the mice that received ES cell transplantation during the experimental period. CONCLUSION: Undifferentiated ES cells developed into hepatocyte-like cells with appropriate integration into tissue, without uncontrolled cell growth. PMID- 17352016 TI - Effects of hypothalamic paraventricular nuclei on apoptosis and proliferation of gastric mucosal cells induced by ischemia/reperfusion in rats. AB - AIM: To investigate the effects of electrical stimulation of hypothalamic paraventricular nuclei (PVN) on gastric mucosal cellular apoptosis and proliferation induced by gastric ischemia/reperfusion (I/R) injury. METHODS: For different experimental purposes, stimulating electrode plantation or electrolytic destruction of the PVN was applied, then the animals' GI/R injury model was established by clamping the celiac artery for 30 min and allowing reperfusing the artery for 30 min, 1 h, 3 h or 6 h respectively. Then histological, immunohistochemistry methods were used to assess the gastric mucosal damage index, the gastric mucosal cellular apoptosis and proliferation at different times. RESULTS: The electrical stimulation of PVN significantly attenuated the GI/R injury at 30 min, 1 h and 3 h after reperfusion. The electrical stimulation of PVN decreased gastric mucosal apoptosis and increased gastric mucosal proliferation. The electrolytic destruction of the PVN could eliminate the protective effects of electrical stimulation of PVN on GI/R injury. These results indicated that the PVN participated in the regulation of GI/R injury as a specific area in the brain, exerting protective effects against the GI/R injury, and the protection was associated with the inhibition of cellular apoptosis and the promotion of gastric mucosal proliferation. CONCLUSION: Stimulating PVN significantly inhibits the gastric mucosal cellular apoptosis and promots gastric mucosal cellular proliferation. This may explain the protective mechanisms of electrical stimulation of PVN against GI/R injury. PMID- 17352017 TI - Effect of BN52021 on NFkappa-Bp65 expression in pancreatic tissues of rats with severe acute pancreatitis. AB - AIM: To investigate dynamic changes and significance of expression of NF kappaBp65 in pancreatic tissues of rats with severe acute pancreatitis (SAP), as well as BN52021 effects. METHODS: Wistar male rats were randomly divided into negative control group (NC group, n=60), SAP-model group (SAP group, n=60), and BN52021-treated group (BN group, n=60), and each of the above groups was respectively divided into 6 subgroups at different time points after operation (1 h, 2 h, 3 h, 6 h, 12 h, and 24 h) (n=10). By RT-PCR and Western blot, NF kappaBp65 mRNA and its protein expression in pancreatic tissues of rats were detected respectively. RESULTS: The expression of NF-kappaBp65 mRNA dynamically changed in both SAP groups and BN groups. The mRNA level was higher in SAP groups than NC groups at 2 h, 3 h, 12 h, and 24 h after operation (P<0.05), higher in BN groups than NC groups at all time points (P<0.05), and higher in BN groups than SAP group at 1 h (P<0.05). The NF-kappaBp65 protein level was higher in SAP groups than NC groups at 1 h, 3 h, and 6 h (P<0.01), and 2 h, 12 h, and 24 h (P<0.05), higher in BN groups than NC groups at all time points (P<0.05), and lower in BN groups than SAP groups at 1 h, 3 h, and 6 h (P<0.05). CONCLUSION: The expression of NF-kappaBp65 in pancreatic tissues is dynamically changed and the changes play an important role in pathogenesis of SAP. BN52021 exerts therapeutic effects through reducing the expression level of NF-kappaBp65 protein in the early stage of SAP. PMID- 17352018 TI - Serum gamma-glutamyltransferase, alanine aminotransferase, and aspartate aminotransferase activity in Iranian healthy blood donor men. AB - AIM: To determine serum gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity, and to assess their correlation with demographic and clinical findings in healthy blood donors. METHODS: This cross-sectional study was performed in 934 male blood donors, aged 18 to 68 years, who consecutively attended Tehran blood transfusion service in 2006. All participants were seronegative for HBV or HCV infections, non alcohol users, and all underwent a standard interview and anthropometric tests. Clinical and biochemical parameters including AST, ALT, and GGT activities were determined. Patients taking drugs known to cause hepatic fat deposition were excluded. For AST, ALT, and GGT variables, we used 33.33 and 66.66 percentiles, so that each of them was divided into three tertiles. RESULTS: Mean AST, ALT, and GGT activities were 25.26 +/- 12.58 U/L (normal range 5-35 U/L), 33.13 +/- 22.98 (normal range 5-35 U/L), and 25.11 +/- 18.32 (normal range 6-37 U/L), respectively. By univariate analyses, there were significant associations between increasing AST, ALT, or GGT tertiles and age, body weight, body mass index, and waist and hip circumferences (P<0.05). By multiple linear regression analyses, ALT was found to be positively correlated with dyslipidemia (B=6.988, P=0.038), whereas ALT and AST were negatively correlated with age. AST, ALT, and GGT levels had positive correlation with family history of liver disease (B=15.763, P<0.001), (B=32.345, P<0.001), (B=24.415, P<0.001), respectively. CONCLUSION: Although we did not determine the cutoffs of the upper normal limits for AST, ALT, and GGT levels, we would suggest screening asymptomatic patients with dyslipidemia and also subjects with a family history of liver disease. PMID- 17352019 TI - Higher radiation dose with a shorter treatment duration improves outcome for locally advanced carcinoma of anal canal. AB - AIM: To assess whether radiation dose and duration of treatment influence local control and survival of patients with locally advanced anal cancer treated with definitive chemoradiation. METHODS: Twenty-eight consecutive patients who were treated with definitive radiation therapy for bulky anal cancers (> 5 cm in size) were reviewed. Nineteen patients had T3 lesions, 8 patients had T4 lesions, and 15 patients had lymph node involvement. The median tumor size was 7.5 cm. All but one patient received concurrent chemoradiation. The median radiation dose was 54 Gy. The median duration of treatment was 58 d. RESULTS: With a median follow-up of 2.5 years in all patients and 7.8 years in living patients, the 2-year local recurrence-free probability was 57% and overall survival rate was 67%. Neither radiation dose nor duration of treatment alone was predictive of either time to local failure or overall survival. However, longer treatment breaks can potentially mask an advantage over higher radiation doses. Therefore, we examined those patients who received >or= 54 Gy within 60 d, comparing them to the rest of the patients. Of patients who received >or= 54 Gy within 60 d, local progression free probability was 89% versus 42% for the rest of the group (P=0.01). CONCLUSION: Local failure is a significant problem in locally advanced carcinomas of the anal canal. Higher radiation doses with limited treatment breaks may offer an increase in local control and survival. PMID- 17352020 TI - Endoscopic sphincterotomy in patients with stenosis of ampulla of Vater: three year follow-up of exocrine pancreatic function and clinical symptoms. AB - AIM: To investigate retrospectively the long-term effect of endoscopic sphincterotomy (ES) including exocrine pancreatic function in patients with stenosis of ampulla of Vater. METHODS: After diagnostic endoscopic retrograde cholangiopancreatography (ERCP) and ES because of stenosis of the ampulla of Vater (SOD Type I), follow-up examinations were performed in 60 patients (mean follow-up time 37.7 mo). Patients were asked about clinical signs and symptoms at present and before intervention using a standard questionnaire. Before and after ES exocrine pancreatic function was assessed by determination of immunoreactive fecal elastase 1. Serum enzymes indicating cholestasis as well as serum lipase and amylase were measured. RESULTS: Eighty percent of patients reported an improvement in their general condition after ES. The fecal elastase 1 concentrations (FEC) in all patients increased significantly after ES. This effect was even more marked in patients with pathologically low concentrations (< 200 microg/g) of fecal elastase prior to ES. The levels of serum lipase and amylase as well as serum alcaline phosphatase (AP) and gamma glutamyltranspeptidase (GGT) decreased significantly after ES. CONCLUSION: The results of this study demonstrate that patients with stenosis of the ampulla of Vater can be successfully treated with endoscopic sphincterotomy. The positive effect is not only indicated by sustained improvement of clinical symptoms and cholestasis but also by improvement of exocrine pancreatic function. PMID- 17352021 TI - Unsedated ultrathin upper endoscopy is better than conventional endoscopy in routine outpatient gastroenterology practice: a randomized trial. AB - AIM: to compare the feasibility and patients' tolerance of esophagogastroduodenoscopy (EGD) using a thin endoscope with those of conventional oral EGD and to determine the optimal route of introduction of small caliber endoscopes. METHODS: One hundred and sixty outpatients referred for diagnostic EGD were randomly allocated to 3 groups: conventional (C)-EGD (9.8 mm in diameter), transnasal (TN)-EGD and transoral (TO)-EGD (5.9 mm in diameter). Pre-EGD anxiety was measured using a 100-mm visual analogue scale (VAS). After EGD, patients and endoscopists completed a questionnaire on the pain, nausea, choking, overall discomfort, and quality of the examination either using VAS or answering some questions. The duration of EGD was timed. Blood oxygen saturation (SaO2) and heart rate (HR) were monitored during EGD. RESULTS: Twenty-one patients refused to participate in the study. The 3 groups were well-matched for age, gender, experience with EGD, and anxiety. EGD was completed in 91.1% (41/45), 97.5% (40/41), and 96.2% (51/53) of cases in TN-EGD, TO-EGD, and C-EGD groups, respectively. TN-EGD lasted longer (3.11 +/- 1.60 min) than TO-EGD (2.25 +/- 1.45 min) and C-EGD (2.49 +/- 1.64 min) (P<0.05). The overall tolerance was higher (P<0.05) and the overall discomfort was lower (P<0.05) in TN-EGD group than in C-EGD group. EGD was tolerated "better than expected" in 73.2% of patients in TN-EGD group and 55% and 39.2% of patients in TO-EGD and C-EGD groups, respectively (P<0.05). Endoscopy was tolerated "worst than expected" in 4.9% of patients in TN-EGD group and 17.5% and 23.5% of patients in TO-EGD and C EGD groups, respectively (P<0.05). TN-EGD caused mild epistaxis in one case. The ability to insufflate air, wash the lens, and suction of the thin endoscope were lower than those of conventional instrument (P<0.001). All biopsies performed were adequate for histological assessment. CONCLUSION: Diagnostic TN-EGD is better tolerated than C-EGD. Narrow-diameter endoscope has a level of diagnostic accuracy comparable to that of conventional gastroscope, even though some technical characteristics of these instruments should be improved. Transnasal EGD with narrow-diameter endoscope should be proposed to all patients undergoing diagnostic EGD. PMID- 17352022 TI - Use of probiotics for prevention of radiation-induced diarrhea. AB - AIM: To investigate the efficacy of a high-potency probiotic preparation on prevention of radiation-induced diarrhea in cancer patients. METHODS: This was a double-blind, placebo-controlled trial. Four hundred and ninety patients who underwent adjuvant postoperative radiation therapy after surgery for sigmoid, rectal, or cervical cancer were assigned to either the high-potency probiotic preparation VSL#3 (one sachet t.i.d.,) or placebo starting from the first day of radiation therapy. Efficacy endpoints were incidence and severity of radiation induced diarrhea, daily number of bowel movements, and the time from the start of the study to the use of loperamide as rescue medication. RESULTS: More placebo patients had radiation-induced diarrhea than VSL#3 patients (124 of 239 patients, 51.8%, and 77 of 243 patients, 31.6%; P<0.001) and more patients given placebo suffered grade 3 or 4 diarrhea compared with VSL#3 recipients (55.4% and 1.4%, P<0.001). Daily bowel movements were 14.7 +/- 6 and 5.1 +/- 3 among placebo and VSL#3 recipients (P<0.05), and the mean time to the use of loperamide was 86 +/- 6 h for placebo patients and 122 +/- 8 h for VSL#3 patients (P<0.001). CONCLUSION: Probiotic lactic acid-producing bacteria are an easy, safe, and feasible approach to protect cancer patients against the risk of radiation induced diarrhea. PMID- 17352023 TI - Self-expandable metallic stents for palliation of patients with malignant gastric outlet obstruction caused by stomach cancer. AB - AIM: To ascertain clinical outcome and complications of self-expandable metal stents for endoscopic palliation of patients with malignant obstruction of the gastrointestinal (GI) tract. METHODS: A retrospective review was performed throughout August 2000 to June 2005 of 53 patients with gastric outlet obstruction caused by stomach cancer. All patients had symptomatic obstruction including nausea, vomiting, and decreased oral intake. All received self expandable metallic stents. RESULTS: Stent implantation was successful in all 53 (100%) patients. Relief of obstructive symptoms was achieved in 43 (81.1%) patients. No immediate stent-related complications were noted. Seventeen patients had recurrent obstruction (tumor ingrowth in 14 patients, tumor overgrowth in 1 patient, and partial distal stent migration in 2 patients). The mean survival was 145 d. Median stent patency time was 187 d. CONCLUSION: Endoscopic placement of self-expandable metallic stents is a safe and effective treatment for the palliation of patients with inoperable malignant gastric outlet obstruction caused by stomach cancer. PMID- 17352024 TI - Clinical considerations and therapeutic strategy for sigmoid volvulus in the elderly: a study of 33 cases. AB - AIM: To evaluate different types of treatment for sigmoid volvulus and clarify the role of endoscopic intervention versus surgery. METHODS: A retrospective review of the clinical presentation and imaging characteristics of 33 sigmoid volvulus patients was presented, as well as their diagnosis and treatment, in combination with a literature review. RESULTS: In 26 patients endoscopic detorsion was achieved after the first attempt and one patient died because of uncontrollable sepsis despite prompt operative treatment. Seven patients had unsuccessful endoscopic derotation and were operated on. On two patients with gangrenous sigmoid, Hartmann's procedure was performed. In five patients with viable colon, a sigmoid resection and primary anastomosis was carried out. Three patients had a lavage "on table" prior to anastomosis, while in the remaining 2 patients a diverting stoma was performed according to the procedure of the first author. Ten patients were operated on during their first hospital stay (3 to 8 d after the deflation). All patients had viable colon; 7 patients had a sigmoid resection and primary anastomosis, 2 patients had sigmoidopexy and one patient underwent a near-total colectomy. Two patients (sigmoidectomy-sigmoidopexy) had recurrences of volvulus 43 and 28 mo after the initial surgery. Among 15 patients who were discharged from the hospital after non-operative deflation, 3 patients were lost to follow-up. Of the remaining 12 patients, 5 had a recurrence of volvulus at a time in between 23 d and 14 mo. All the five patients had been operated on and in four a gangrenous sigmoid was found. Three patients died during the 30 d postoperative course. The remaining seven patients were admitted to our department for elective surgery. In these patients, 2 subtotal colectomies, 3 sigmoid resections and 2 sigmoidopexies were carried out. One patient with subtotal colectomy died. Taken together of the results, it is evident that after 17 elective operations we had only one death (5.9%), whereas after 15 emergency operations 6 patients died, which means a mortality rate of 40%. CONCLUSION: Although sigmoid volvulus causing intestinal obstruction is frequently successfully encountered by endoscopic decompression, however, the principal therapy of this condition is surgery. Only occasionally in patients with advanced age, lack of bowel symptoms and multiple co-morbidities might surgical repair not be considered. PMID- 17352025 TI - Validity and cost comparison of 14carbon urea breath test for diagnosis of H Pylori in dyspeptic patients. AB - AIM: To validate and compare the cost of microdose 14C urea breath test (UBT) with histology and rapid urease test for the diagnosis of H Pylori. METHODS: Ninety-four consecutive patients with dyspeptic symptoms undergoing gastroscopy were enrolled. Gastric biopsies were taken for histology and rapid urease test. UBT was performed after gastroscopy by microdose 14C urea capsules. Sensitivity, specificity and accuracy of UBT were calculated and compared with histology and rapid urease test. Cost comparison of these tests was also performed. RESULTS: H pylori was diagnosed by histology and rapid urease test in 66 (70%) and 61 (65%) patients, while 14C UBT detected infection in 63 (67%). Accuracy of UBT was 93% in comparison with histology while its positive and negative predictive values were 97% and 84%, respectively. Comparison of 14C UBT with rapid urease test gives an accuracy of 96%, with positive and negative predictive values of 95% and 97%, respectively. These results were highly reproducible with a Kappa test (P value<0.001). Cost of histology or rapid urease test with gastroscopy was 110 USD or 95 USD respectively while the cost of UBT was 15 USD. CONCLUSION: Microdose 14C UBT was comparable to histology and rapid urease test. 14C UBT is an economical, self sufficient and suitable test to diagnose active H pylori infection in less developed countries. PMID- 17352026 TI - Omeprazole-based triple therapy with low-versus high-dose of clarithromycin plus amoxicillin for H pylori eradication in Iranian population. AB - AIM: To investigate the efficacy and tolerability of H pylori eradication in an omeprazole-based triple therapy with high- and low-dose of clarithromycin and amoxicillin. METHODS: One hundred and sixty H pylori positive patients were randomly assigned to two groups based on the following 2 wk investigation; (1) group A or low-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 250 mg b.i.d and amoxicillin 500 mg b.i.d; and (2) group B or high-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 500 mg b.i.d and amoxicillin 1000 mg b.i.d. During the study H pylori status was assessed by histology and rapid urease test prior and by (13)C-urea breath test 6 wk after the therapy. Standard questionnaires were administered to determine the compliance to treatment and possible adverse events of therapy. Data were subject to chi2 to compare the eradication rates in the two groups. The significant level of 95% (P or = 16 years from Southern Estonia during 2002-2003 (n = 185) were interviewed. HSD was defined as the interval from a patient's first contact with a medical provider to the date of TB diagnosis. RESULTS: The factors significantly associated with HSD greater than the median (19 days) and the 75th percentile (40 days) were smear negativity, absence of cough among symptoms, absence of chest X-ray during the first visit and age > 60 years. A significantly shorter HSD was determined in non-Estonians and unemployed patients. HSD was not associated with the specialty of the doctor first contacted by the patient. CONCLUSION: This study in Southern Estonia shows that the health care system is still managing the diagnosis of PTB without significant delays, even after substantial modifications in the health care system resulting from social reform in a post-socialist country, and that family physicians can manage PTB patients successfully. PMID- 17352093 TI - Additional risk of developing TB for household members with a TB case at home at intake: a 15-year study. AB - OBJECTIVE: To assess the additional risk to household contacts from an infectious case of tuberculosis (TB) at home in a rural community in south India. METHODS: In all, 3506 contacts of smear-positive (S+C+) and 2910 contacts of smear negative TB cases (S-C+) and 246 845 persons with no TB case at home were followed for 15 years, with a repeat survey every 2.5 years consisting of radiographic and sputum examination, selective follow-up of high-risk individuals and passive surveillance. If a case developed during follow-up, all household members were subsequently considered as contacts. Cox's proportional hazards model (multivariate) was employed to compare incidences. RESULTS: The annual incidence of culture-positive TB was respectively 526 and 271 per 100000 population for contacts of smear-positive and smear-negative patients, and 198/100000 in non-contacts. The adjusted hazard rate was 3.4 for contacts of smear-positive patients (95% CI 3.0-3.9) and 1.7 for contacts of smear-negative patients (95% CI 1.4-2.0) as compared to non-contacts. Of 3942 incident cases, 337 (8.5%) came from households with a TB case. CONCLUSION: Although family contacts had a significantly higher incidence, their contribution to total new caseload was meagre. Contact chemoprophylaxis as a public health measure would therefore have limited impact on community TB incidence. PMID- 17352094 TI - Results of directly observed treatment for tuberculosis in Ensenada, Mexico: not all DOTS programs are created equally. AB - SETTING: Tuberculosis (TB) program in Ensenada, Mexico. OBJECTIVE: To evaluate the impact of the DOTS strategy on adherence and cure rates in everyday practice. DESIGN: Retrospective analysis of 629 patients diagnosed with TB. MEASUREMENTS AND RESULTS: A total of 70% of the patients under directly observed treatment (DOT) were cured vs. 72.8% of those under self-administered treatment (SAT, P = 0.57). There was no difference on the length of therapy according to treatment regimen (4.82 +/- 2.41 for DOT vs. 4.93 +/- 2.16 for SAT, P = 0.61); 16.8% of patients under DOT abandoned treatment vs. 14.1% in the SAT group (P = 0.40). Logistic regression analysis confirmed the previous findings, with length of treatment under 6 months being the strongest predictive variable for treatment failure (OR 18.8, P < 0.00). The type of regimen (DOT vs. SAT) was not predictive of treatment failure (OR for failure for SAT regimen 0.65, P = 0.14). CONCLUSIONS: Cure and completion of treatment rates in our population under study did not differ significantly when comparing DOT vs. SAT. Those in charge of the DOTS programs in a given country need to assess which are the most important ingredients for success in their particular program. PMID- 17352095 TI - Operational conditions influencing the proficiency of AFB microscopy services in the Philippines. AB - SETTING: The microscopy services of the Philippine National Tuberculosis Programme (NTP). OBJECTIVE: To investigate how operational conditions in field microscopy centres (MC) affect proficiency. DESIGN: In 2004, a newly developed external quality assessment system (blinded rechecking) for acid-fast bacilli (AFB) microscopy employing lot quality assurance sampling (LQAS) was introduced into the NTP by the Philippine government. Performance reported by the quality assurance centres (QACs) of the four provinces and four cities was analysed. RESULT: There was no significant difference in rechecking results between small MCs examining fewer than 166 slides (500 slides/3 sputum samples per suspect) and larger MCs in the provinces. City MCs recorded better performance than those of the provinces. A city QAC covers only five MCs in average, whereas a provincial QAC covers 38. The average distance between city QACs and MCs is much shorter (3.2 km) than in the provinces (60.5 km). CONCLUSION: The number of MCs to be covered by each QAC and the distances between QAC and MCs are the dominant factors influencing the quality of AFB microscopy. Combining a few neighbouring MCs to reduce the number of MCs and/or provision of sufficient travel funds and timely use of vehicles, particularly in the provinces, are recommended. PMID- 17352096 TI - Validation of candidate smear microscopy quality indicators, extracted from tuberculosis laboratory registers. AB - SETTING: Kinshasa Province, Democratic Republic of Congo. OBJECTIVE: To identify and validate register-based indicators of acid-fast bacilli (AFB) microscopy quality. DESIGN: Selection of laboratories based on reliability and variation in routine smear rechecking results. Calculation of relative sensitivity (RS) compared to recheckers and its correlation coefficient (R) with candidate indicators based on a fully probabilistic analysis incorporating vague prior information using WinBUGS. RESULTS: The proportion of positive follow-up smears correlated well (median R 0.81, 95% credibility interval [CI] 0.58-0.93), and the proportion of first smear-positive cases fairly (median R 0.70, 95% CI 0.38-0.89) with RS. The proportions of both positive suspect and low positive case smears showed poor correlations (median R 0.27 and -0.22, respectively, with ranges including zero). CONCLUSIONS: The proportion of positives in follow-up smears is the most promising indicator of AFB smear sensitivity, while the proportion of positive suspects may be more indicative of accessibility and suspect selection. Both can be obtained from simple reports, and should be used for internal and external monitoring and as guidance for supervision. As proportion of low positive suspect smears and consistency within case series are more difficult to interpret, they should be used only on-site by laboratory professionals. All indicators require more research to define their optimal range in various settings. PMID- 17352097 TI - Auto-antibody profiles in patients with active pulmonary tuberculosis. AB - OBJECTIVES: To determine the prevalence of a wide array of auto-antibodies in patients with tuberculosis (TB) compared with healthy controls. MATERIALS AND METHODS: Forty-seven consecutive patients (age 47 +/- 21 years, 29 males) with recently diagnosed active pulmonary tuberculosis (PTB) and 39 healthy controls were enrolled. Data collected on a questionnaire included clinical features of the disease, duration of symptoms, presence of fever, cough, arthralgia, myalgia, sicca symptoms and others. Serum samples were collected from the patients' before initiating TB treatment, frozen at -20 degrees C and tested for antinuclear antibodies (ANA), anti-ds DNA, anti-Sm, anti-RNP, anti-Ro, anti-La, and anti cardiolipin (ACA) (IgG and IgM). RESULTS: Rheumatic symptoms were relatively rare: arthralgia (n = 2), myalgias (n = 2), and eye (n = 1) and mouth dryness (n = 4). The TB patients' mean serum levels of anti-ds DNA, anti-Sm, anti-RNP, anti SSA (anti-Ro), and anti-ACA-IgM were significantly increased compared with controls (P < 0.05 for all). A significantly higher proportion of TB patients had increased pathological levels of anti-ds DNA (32% vs. 2.5%), anti-Sm (38% vs. 0%), anti-RNP (15% vs. 0%), anti-Ro (64% vs. 10%), anti-ACA-IgG (59% vs. 0%) and anti-ACA-IgM (47% vs. 7.7%) (P < 0.05 for all). CONCLUSIONS: Patients with active TB have significantly increased titres of various auto-antibodies, including highly specific serological markers, such as anti-Sm. RELEVANCE: Differential interpretation of serological studies of patients with systemic manifestations should consider the possibility of PTB. PMID- 17352098 TI - Predominance of a single genotype of Mycobacterium tuberculosis in regions of Southern Africa. AB - SETTING: Zimbabwe and Zambia. OBJECTIVE: To determine the genetic diversity of Mycobacterium tuberculosis strains isolated from tuberculosis (TB) patients in Zimbabwe and Zambia. DESIGN: M. tuberculosis isolates cultured from TB patients presenting at referral hospitals in Zimbabwe and health care clinics in Zambia were characterised by IS6110 genotyping and/or spoligotyping using internationally standardised methods. Genotypic data were compared to those from Cape Town and the SpolDB3.0 database. RESULTS: A predominant group of strains could be identified among 116/246 (47.2%) Zimbabwean isolates by their characteristic IS6110-banding pattern and unique spoligotype signature, where spacers 21-24, 27-30 and 33-36 were deleted. Comparison with strains from Cape Town showed that they were closely related to a family of strains present in 2.3% of Cape Town patients. Comparison of the spoligotypes with those obtained from 114 isolates from Zambia showed that 74 (65%) of these isolates had the same spoligotype signature. Spoligotypes in the SpolDB3.0 database showed that this group of strains was rarely isolated in other parts of the world, but was commonly isolated in Southern Africa. CONCLUSION: A predominant group of strains infecting approximately half of the patients in the study are major contributors to the TB epidemic in this region. We have designated this group of strains the Southern Africa 1 (SAF1) family. PMID- 17352099 TI - Impact of short-term exposure to fluoroquinolones on ofloxacin resistance in HIV negative patients with tuberculosis. AB - SETTING: Seoul, Korea, a country with an intermediate tuberculosis (TB) burden and low prevalence of human immunodeficiency virus (HIV) infection. OBJECTIVES: To determine the frequency of ofloxacin (OFX) resistance in Mycobacterium tuberculosis, and to assess whether short-term use of fluoroquinolones (FQNs) induces ofloxacin-resistant M. tuberculosis. DESIGN: The subject cohort consisted of 2788 patients with culture-confirmed TB with drug susceptibility testing data; only four were HIV-positive. The patients were divided into two groups: those who were or were not recently exposed to FQNs. RESULTS: Of the 2788 isolates, the rates of OFX resistance were 1.1% and 8.5% in initially treated and retreated patients, respectively (P < 0.05). Of the 94 OFX-resistant isolates, 83 (88.3%) were multidrug-resistant (MDR). There was no difference in rates of OFX resistance throughout the study period, or between the FQN-exposed (1/39, 2.6%) and control groups (93/2749, 3.4%). The median duration of FQN treatment was 7 days (range 1-47 days). One OFX-resistant isolate in the FQN-exposed group was MDR. CONCLUSION: The rate of OFX-resistant M. tuberculosis was low and stationary throughout the study period in Korea. Most OFX resistance was accompanied by MDR, and the frequency of OFX-resistant M. tuberculosis was low in subjects taking short-term FQNs. PMID- 17352100 TI - Impact of drug-resistant tuberculosis on the survival of HIV-infected patients. AB - OBJECTIVE: To determine the effect of drug-resistant tuberculosis (TB) on the survival of human immunodeficiency virus (HIV) infected patients in an area with a high prevalence of TB. DESIGN: Retrospective cohort study. RESULTS: Of 225 HIV TB patients with a mean age of 35.8 years, 72.4% were male. The median CD4 cell count at TB diagnosis was 44 cells/mm3. Sixty per cent presented with extra pulmonary TB (EPTB). Sixty-three (28%) patients were infected with Mycobacterium tuberculosis resistant to at least one drug; respectively 16.4%, 9.3%, 5.3% and 12.9% were resistant to isoniazid (INH), rifampicin (RMP), ethambutol and streptomycin, and 14 (6.2%) had multidrug-resistant TB (MDR-TB). During a median follow-up of 11.5 months, 4% died. From Kaplan-Meier analysis, INH resistance, RMP resistance and MDR-TB were associated with shorter survival (log-rank test, P < 0.005). Cox's proportional hazard model showed that MDR-TB (hazard ratio [HR] 11.7; 95% CI 2.1-64.9), not receiving antiretroviral therapy (ART) (HR 7.9; 95% CI 1.5-43.1) and EPTB (HR 5.1; 95% CI 1.9-25.9) were significant risk factors for death. CONCLUSION: MDR-TB and EPTB substantially reduce survival among patients co-infected with HIV and TB. Early detection and optimal treatment of MDR-TB are crucial. ART significantly prolongs survival and should be initiated in HIV-TB co infected patients. PMID- 17352101 TI - Mycobacterium kansasii in HIV patients: clarithromycin and antiretroviral effects. AB - SETTING: Charity Hospital New Orleans, Louisiana, USA. OBJECTIVE: To define the differences between the pre-HAART (highly active anti-retroviral treatment) and HAART eras in patients co-infected with Mycobacterium kansasii and the human immunodeficiency virus (HIV). DESIGN: A retrospective chart review revealed 82 patients with HIV and M. kansasii during the 6-year period from 1 July 1991 to 30 June 1997 (pre-HAART era), while the 6-year period from 1 July 1997 to 30 June 2003 (HAART era) revealed 55 cases. RESULTS: Among all patients with M. kansasii and HIV, 47 (34%) had an additional, concurrent mycobacterial infection and two had triple mycobacterial species isolation. More patients (17/82, 21%) had disseminated mycobacterial disease in the pre-HAART era than in the HAART era (3/55, 5%; P = 0.045). Pre-HAART patients treated without clarithromycin (CLM) survived a median of 2 months vs. 10 months for pre-HAART patients treated with CLM (P = 0.05). Those treated without CLM had a median survival of 2 months in the pre-HAART era (n = 19) vs. 10.5 months in the HAART era (n = 12, P < 0.02). CONCLUSION: CLM use in treatment of M. kansasii in HIV-co-infected patients is associated with significantly longer survival. PMID- 17352102 TI - A longitudinal study of changes in respiratory status in young adults, 1993-2001. AB - SETTING: There is little information regarding the prognosis of respiratory symptoms in early adulthood or the effects of potential risk factors. OBJECTIVE: To observe changing respiratory morbidity in a group of young adults over a period of 6-8 years. DESIGN: Subjects responding to three or more consecutive postal respiratory surveys carried out between 1993 and 2001 were included in the study. In addition to asthma (defined by a validated scoring system), two symptoms were examined: wheeze and being woken by cough. Five outcomes were defined: persistent, remission, new onset, never and intermittent. RESULTS: Of 2693 subjects who responded to at least one survey, about one third were eligible for inclusion: 10.2% reported wheeze at each survey (persistent) and 3.6% had persistent asthma. Persistent wheeze was seen in almost half (46.7%) of those reporting the symptom at their first survey. The corresponding figure for asthma was 32%. New onset wheeze was found in 16.2% of subjects without wheeze at baseline (asthma 9.7%). Smoking was significantly associated with new onset wheeze (OR 1.97, 95% CI 1.30-3.00) and asthma (OR 2.14, 95% CI 1.26-3.50), but not with persistent symptoms. CONCLUSION: These findings highlight the importance of policies to reduce smoking prevalence in young adults, and will help in the planning of future health care. PMID- 17352103 TI - Attitudes of private pharmacists in the management of asthma patients in Lome. AB - BACKGROUND: Optimal asthma management requires interventions by a number of health professionals, including pharmacists. OBJECTIVE: To assess the attitudes of pharmacists towards asthma patients and to evaluate their knowledge about how to use the metered dose inhaler. METHODS: A descriptive survey through self administered questionnaire was conducted among pharmacists in private pharmacies in Lome, Togo. Pharmacists who did not respond before the sixth round of the investigator were excluded from the study. RESULTS: The participation rate was 76.4%. All pharmacists stated that asthma patients visited their pharmacies during and/or between acute episodes. Some asthma patients visited the pharmacies without prior medical prescription. Asthma drugs were delivered without medical prescription, particularly during acute episodes. In case of acute episodes, care was provided by 51.2% of pharmacists. Aerosol devices were the most widely used treatment, although the technical procedures required for correct inhalation were found to be poorly understood by 27.4% of the pharmacists. Pharmacists provided recommendations to patients on long-term treatment, regular medical follow-up and avoidance of allergens and tobacco smoking. CONCLUSION: Rather than limiting their action to dispensing drugs, pharmacists can also become involved in educating asthma patients. PMID- 17352104 TI - Rising ELISPOT count prior to the onset of symptoms of full-blown tuberculosis disease. AB - The relationship between the T-cell response to mycobacterial antigens and the likelihood of progression to disease has not been defined. We report a rapidly rising ELISPOT count in a 55-year-old man with evidence of Mycobacterium tuberculosis infection prior to the onset of symptoms of disease. This case illustrates the possible utility of quantitative changes in the ELISPOT count in predicting progression from M. tuberculosis infection to disease. PMID- 17352105 TI - Diagnosis and treatment of latent tuberculosis. PMID- 17352106 TI - [Digestive interventional endoscopy in pediatrics]. AB - With development and improvement of the endoscope equipment, the paediatric endoscopy is developing from the diagnosis endoscopy to the interventional endoscopy. It is realized under general anaesthesia as a minimal invasive surgery and it is necessary to regularize the legal requirements. The main acts are realized in a current way in paediatrics endoscopy units: extraction of foreign body, dilation of oesophageal strictures, gastrostomy, polipectomy. Other indications are less frequent: injection sclerotherapy, haemostasis of upper GI bleeding or endoscopic achalasia treatment. The biliary and/or pancreatic lesions is rare in children, in these cases, interventional endoscopy is usually done with the collaboration of the adult endoscopists, with a far experience. Interventional endoscopy is a safe and effective technique that can be performed in all the pediatrics endoscopy units. PMID- 17352107 TI - [Therapeutic strategy in cloacal exstrophy]. AB - Cloacal exstrophy is a complex multisistemic anomaly that involves gastrointestinal and genitourinary issues. The aim of our paper is to report our experience in dealing with genital reconstruction and faecal and urinary continence in patients with female cloacal anomalies. We reviewed the clinical records from the three patients we have achieved a final reconstruction. We recorded the surgical management and both functional and anatomic results. The three of them required a bladder neck closure associated with a continent stoma, they are dry with intermittent catheterization and free of upper urinary complications. Genital reconstruction required a unique plan for each one, according to their anatomy and their cosmetic desires. One of the patients reported satisfactory sexual intercourse. Management of patients with cloacal exstrophy has major concerns about urinary and fecal continence and about genital reconstruction and function. Knowing the long-term results may help to develop management strategies and improve counselling for patients who have under-gone reconstruction. PMID- 17352108 TI - [Congenital portosystemic shunt. The Abernethy malformation]. AB - BACKGROUND: Congenital portosystemic shunt (CEPS) is a rare condition that was first reported by John Abernethy in 1793. Two types of CEPS are described: type I (side to end anastomosis) or congenital absence of the portal vein, and type II (side to side anastomosis) with portal vein supply partially conserved. Type I CEPS is usually seen in girls and associates multiple malformations as polysplenia, malrotation, and cardiac anomalies. Type II is even rarer with no sex preference and no malformations associated. Hepatic encephalopathy is a common complication of both types in adulthood. Liver transplantation is the only effective treatment for symptomatic type I CEPS. A therapeutic approach for type II could be surgical closure of the shunt. OBJECTIVE: To analyse our experience in diagnosis and management of portosystemic shunts. METHODS: We report 4 cases of CEPS (3 type I and 1 type II) diagnosed between January-1997 and March-2005 in our department. RESULTS: We present 4 patients with ages at diagnosis ranging from 0 to 28 months, 3 type I CEPS (2 boys and 1 girl) and 1 boy type II. The type I girl was prenatally diagnosed at 12 weeks of gestation. Initial clinical signs in type 1 boys were splenomegaly and hypersplenism, both with normal pondo statural growth. No polysplenia or cardiac anomalies were assessed. One of them presented mild developmental delay, dismorphic features and facial telangiectasias. He had normal coagulation tests with chronic hepatic dysfunction (high transaminases) and regenerative nodular lesions were seen by imaging techniques. The other type I patient had hypoprothrombinemia, tendency to capillary bleeding (haematomas and epistaxis) with preserved liver function. Both patients have developed mild portal hypertension and present steatosis signs at liver biopsy. The type I girl presents a 21 trisomy and associates a cardiac anomaly (interauricular communication). Her hepatic function test are normal but liver calcifications can be seen by ultrasound. Type II child associates hypospadias but he has no clinical sigh or symptom related to the shunt. In our three cases diagnosis was suggested by conventional and Doppler ultrasound and confirmed by angio-resonance imaging. All our patients are included in a meticulous clinical and radiological follow-up with no need of surgical treatment for the shunt until now. CONCLUSIONS: Although diagnosis of these malformations could be casual we have to think about CEPS in children presenting unspecific liver disease. Magnetic angio-resonance imaging is actually the best diagnosis methods for CEPS. These patients have a high risk for developing hepatic encephalopathy and portal hypertension, so a careful follow-up is required although surgery is not usually needed until adulthood. PMID- 17352109 TI - [Soft tissue sarcomas (1991-2004)]. AB - BACKGROUND: The aim of this study is to review the results of the treatment of soft tissue sarcomas (STS) in our Department during the last 13 years. MATERIAL AND METHODS: Fifty-seven children (39 rhabdomyosarcomas (RMS) and 18 other types of sarcomas) have been treated. Nineteen RMS were excluded because they were treated by oher departments. The charts of 39 chidren were analysed evaluating several parameters (age, sex, location, histology, initial stage, clinical and surgical treatment and results) as prognostic factors using actuarial survival analyses and log-rank tests. RESULTS: 1. RMS: Median age at diagnosis was 2.3 years (range 6 m-16y). Twelve were genitourinary, 3 thoracic, 3 abdominal, 1 was located in limb and 1 in the neck. Histologically, 13 were embryonal, 5 botryoid, 1 alveolar and 1 fusiform. At diagnosis, 74% were in stages I or II. Fine needle aspiration biopsy (FNAB) was made in 5 children and the result was always imprecise or mistaken. Surgical biopsy was made before the definitive surgery in 12 cases. In the remaining 8 children the diagnosis was made only after surgical resection. With an mean follow-up of 70 +/- 43 moths, 6 children died. The prognostic factors associated with poor outcomes were genitourinary location, non radical excission, the presence of distant metastases at onset and alveolar histology. 2. Other sarcomas: Median age at diagnosis was 10.9 years (range 4 days-15 years). Among this group, there were 6 fibrosarcomas, 4 indifferentiated sarcomas, 3 synovial sarcomas, 2 abdominal desmoplastic small round cell tumours, 2 neurofibrosarcomas and 1 leiomyosarcoma. Only 9 received chemotherapy and one radiotherapy. All but one were operated. Five out ot the 19 died. CONCLUSIONS: Although the role of surgery is crucial, it is necessary to refine the initial histological diagnosis, because neither the PAAF or the biopsy have always been correct. The negative prognostic factors in our series were metastases present at diagnosis, genitourinary location and alveolar (RMS), desmoplastic or indifferenciated histology. PMID- 17352110 TI - [Esophageal replacement. 12 years experience]. AB - Esophageal replacement is a surgical procedure rarely indicated in children. It is used in esophageal atresia type I and long-gap atresia when anastomosis is not possible, corrosive strictures and other unusual causes. Type and location of the graft depend on etiology and surgeon preferences. We analyse our results of a large series of esophageal replacement. METHODS: . We reviewed esophageal replacements carried out in our department between January-1992 and December 2004. We report 29 patients (15 girls and 14 boys) with ages ranging from 2 months until 14 years old (median 24 months). 11 (37.9%) had esophageal atresia type I, 7 (24.1%) long-gap esophageal atresia, 8 (27.5%) caustic esophagitis, 1 herpetic esophagitis, 1 candida esophagitis and 1 esophageal necrosis due to sclerotherapy. Colon was used for substitution in 25 cases (86.2%) and stomach in 4 (13.8%). Graft location was retromediastinal in 25 children (86.2%), retrosternal in 3 and subcutaneous in 1. Native esophagus was removed in all but 2 out of 3 retrosternal cases. RESULTS: After a follow up between 7 and 145 months (median 76 months) all children have a functional graft. Actually all patients tolerate oral feeding in a satisfactory way, and have had a normal pondostatural growth. Post-operative complications were pyloric obstruction in 3 patients (10.3%), upper anastomosis stricture in 3 (10.3%), 2 (6.9%) surgical wound evisceration, 2 (6.9%) diaphragmatic hernia, 1 (3.4%) retro-mediastinal abscess and 1 (3.4%) colo-gastric emptying difficulties. Also 2 pleural effusions, 1 cervical wound abscess and 1 abdominal wound one. Re-operation was needed in 11 patients (38%) due to these adverse events. Other complications were conservatively solved: 6 (20.7%) salivary fistula, 1 intestinal suboclusion and a dumping syndrome. One girl died due to a mycotic mediastinal abscess with perforation of the aorta 11 days after surgery. Overall survival was 96.5%. CONCLUSIONS: Esophageal replacement has limited indications. It allow a good functional result, with adequate oral feeding and normal growth. We believe that both colon and stomach have similar outcomes, but gastric pull-up is easier to perform. It is a major surgery whose risk of complications is higher in early post-operative time. PMID- 17352111 TI - [Primary lung tumors]. AB - Pulmonary neoplasia in children is usually due to methastatic disease because primary lung tumors are very unfrequent. Due to its' rarity they are usually not included in the differential diagnosis of lung masses, so treatment is delayed and prognosis is worsened. Herein, we show our experience in the management of five primary tumors of the lung or the airway: one tracheal, three bronchial, and another intraparenchymatous. We study the clinical behaviour, diagnostic work-up, treatment, histology, and follow-up. Despite its rarity, a diagnosis of pulmonary tumor should be considered in any child with respiratory symptoms that does not improve with standard therapy. An early and accurate diagnosis and an adequate treatment are crutial in the prognosis of these patients. PMID- 17352112 TI - [The role of surgery for lung nodules in pediatric oncology]. AB - AIM: To evaluate the role of lung nodule surgery in pediatric cancer patients. MATERIALS AND METHODS: The records of all cancer patients (< 18 y) treated at our pediatric institution since 1993 were reviewed. Clinical data, imaging features, surgical attitude, pathology and outcome were analyzed for those patients developing lung nodules on CT scan at any time. RESULTS: Fifty-seven out of 857 (6.6%) cancer patients had lung nodules at one or more times during their disease course, totalling seventy-five episodes. The primary pathological diagnoses include: Osteosarcoma n = 17, Ewing's sarcoma n = 14, Rhabdomyosarcoma n = 5, Germ cell tumor n = 4, other sarcomas n = 4, Wilms' tumor n = 3, Neuroblastoma n = 3, Lymphoma n = 2. Twenty-nine cases had lung nodules at diagnosis; in 20 they were found during therapy; in 29 concomitant with other sites of relapse off therapy; and in 16 patients as an isolated event during follow-up. Fifty-five biopsy procedures were performed through thoracotomy, thoracoscopy or pleural effusion cytology. Metastasic disease was confirmed in 46, whereas in 9 no malignancy was found. Among the nine, five showed either normal lung tissue or scarring after tumor necrosis, and four had other benign diagnoses including: reactive inflammatory cells, pleural lymphangioma, mycobacteria infection and inflammatory pseudotumor. In 39 instances biopsy was not done either because the diagnosis could be made through specific tests, or because the nodules disappeared in a follow-up CT scan within 2 weeks, or because of disease progressing in spite of treatment. In 4 patients surgical removal of lung metastases has afforded cure. CONCLUSIONS: Lung nodule surgery plays a fundamental role in the management of patients with pediatric malignancies: it allows accurate staging, avoiding overtreatment in more than 15% of the cases, and gives a higher chance of cure in some patients. PMID- 17352113 TI - [Are there some clinical factors that indicate the best moment of the surgery in the congenital diaphragmatic hernia?]. AB - AIM: To determine if the needs of cardiopulmonary support of neonates with congenital diaphragmatic hernia (CDH) they can be indicators for the election of the most suitable moment to the surgery. METHODS: We treated 16 consecutive neonates with congenital diaphragmatic hernia (CDH) from 2004 to 2005. Mean birth weight was 2900.63 +/- 531.51 g. Patients was divided in 2 groups. Group A: newborns without adrenaline nor noradrenaline like vasoactive drugs and conventional respiratory assistant; the surgery was performed during the first 48 hours of life. Group B: newborns with adrenaline or noradrenaline like vasoactive drugs, high-frequency oscillatory ventilation or extracorporeal membrane oxygenation; surgery was delayed (10.66 +/- 8.26 days). RESULTS: Four neonates died during the first 24 hours of life without surgical treatment not fulfilling criteria of support ECMO. Five patients were operated during the first 48 hours, fulfilling all of them the clinical criteria of the group A. Mortality does not exist in this group. Seven patients were operated late fulfilling the criteria of the group B. They all needed VAFO. Two patients of this group needed support ECMO. The survival rate in this group was 83.3%. DISCUSSION: In our opinion, the patients with CDH that need initially high cardiopulmonary support, VAFO and/or ECMO would be necessary a time of wait to realize the surgery. In those patients who don't need this level of treatment the delay would not justify itself in the surgical intervention. PMID- 17352114 TI - [Pandrial gastroesophageal reflux in healthy preterm infants]. AB - The neutralization of gastric content during feeding and in the immediate postpandrial period, has determined that until recently time these periods were excluded in the studies of the gastroesophageal reflux disease (GERD) that were made with pH-metria. The aim of this study was to characterize the events of reflux during feeding with pH and impedance,and later to compare them with which it happens in fasting periods. MATERIAL AND METHOD: We recording pH and Impedance in 21 preterms neonates without associated pathology, except the prematurity, during 8 periods of feeding-fasting (1 hour of feeding and 2 hours of rest), replacing the nasogastric tube by a catheter of feeding + impedance, previous informed consent. RESULTS: The average of reflux during the meals per hour was of 3.36 h +/- 1.23 h, whereas in fasting periods was 1.02 h was of 2.65 h +/- (p = 0.068). The number of acid reflux per hour during the fasting was higher [1, 05 (0.34-1.23) h] than in feeding periods [0, 20 (0-1.12) h] (p = 0,044). The number of weakly acid reflux per hour was significantly higher in feeding periods [2, 71 (2.03-3.30) h] than in fasting periods [1, 35 (1.13-1.97) h] (p = 0, 05). The acid exposure during the meals was of 2, 35% whereas in fasting periods was of 7, 23%. CONCLUSION: The incorporation of the Impedance within the battery of tests for the diagnosis of the gastroesophageal reflux in the pediatric population, at the moment allows us to know the pattern behavior of esophagus during the meals: feeding periods were associated with a greater number of reflux per hour, most of which weakly acidic; the acid exposure was significantly greater during fasting periods. PMID- 17352115 TI - [Pyomyositis of hip obturator muscles]. AB - Obturator internus muscle abscess (pyomyositis) is extremely rare in temperate environments, although there has been a recent reported increase in prevalence. There usually is a delay in diagnosis and onset of treatment. In addition to our case, we reviewed all cases of pyomyositis of hip muscles found in a review of the recent medical literature. PMID- 17352116 TI - [Pure gonad dysgenesia or Swyer sindrome. A case report having tumoral development: melanoma]. AB - A 14 year old girl having 10-days lumbar pain, polaquiuria and moderate pain to palpation is reported. Blood and urine analysis were normal. Abdominal ultrasound scan showed cavity free and solid, rounded, heterogeneous, intrapelvic mass compressing bladder and uterus. Magnetic resonance image was performed showing right gonad compromise with extensive liver and sacro-lumbar spine invasion. Tumoral markers were ruled out. During surgery, primary tumor mass localizad in the right gonad was completely excised. Melanotic peritoneal and hepatic disemination were observed. The patient had left streak gonad and infantile uterus (2 x 3 cm). As gonad dysgenesia was suspected, high resolution cromosomic study was performed and resulted in cariotype 46 XY. Microscopy of the resected gonad showed primary gonad melanoma. Chemotherapy was instituted with no tumor response and the patient died two month later. PMID- 17352117 TI - [Gastric volvulus]. AB - Gastric volvulus is a rare condition in pediatric population in which there is an abnormal rotation of one part of the stomach around itself. It's a surgical emergency. We report a six year old female admitted in the emergency due to upper abdominal distention, nausea without vomiting, physical exam revealed upper abdominal distention and abdominal tenderness, no bowel sounds. Laparotomy was performed and a gastric volvulus with occlusive vascular involvement was found. In the post operative period she required a second laparotomy due to adhesions in small bowel. PMID- 17352118 TI - [An association of mucocele and carcinoid tumour of the appendix]. AB - The carcinoid tumour of the appendix and the mucocele are entities rather infrequent in children and are normally diagnosed in the course of an appendicectomy that is, in most of the cases, curative. The association of both processes is unusual. The authors present a case of carcinoid tumour of the appendix associated to mucocele in a male, aged 10 patient, who underwent an appendicectomy by suspicion of an acute appendicitis. The histologic study confirmed the presence of a mucocele of the appendix associated to a carcinoid tumour with a 0,7 cm diameter. The serum serotonin and chromogranin A assessment was normal, and the TAC and colonoscopic examination resulted in no meaningful findings. The appendicectomy itself was curative, deeming it the appropiated treatment in tumours under 2 cm diameter. PMID- 17352119 TI - Globalization of environmental research. PMID- 17352120 TI - Facing hazardous matter in atmospheric particles with NanoSIMS. AB - Current scientific studies and evaluations clearly show that an increase of urban dust loads, alone or in combination with other air pollutants and certain meteorological conditions lead to different significant health effects. Premature death, increased hospital admissions and increased respiratory symptoms and diseases as well as decreased lung function can be observed in combination with high pollutant levels. Sensitive groups like elderly people or children and persons with cardiopulmonary diseases such as asthma are more strongly affected. Because of the direct contact between fine particles and lung tissue more information concerning the surface structure (mapping of toxic elements) is required. The NanoSIMS 50 ion microprobe is used to image the elemental composition at the surface of submicrometer particles. Imaging the ions of the samples under cesium bombardment identifies the organic and inorganic origins of the grains. Our investigations show that the atmospheric fine dust consists of a complex mixture of organic and inorganic compounds. Heavy metals are fixed on airborne particles in the form of hot spots in a nanometer scale. In regard to the health aspect, the hot spots consisting of toxic elements are particularly relevant as they react directly with the lung tissues. PMID- 17352121 TI - Production of ethanol by an integrated valorization of olive oil byproducts the role of phenolic inhibition. AB - Agricultural industrial wastes can frequently be used as raw materials in the production of bio-fuels. Olive-oil milling wastewater is considered as one of the most polluting agro-industrial residues, but fortunately due to its high content of organic matter, it has the potential to be a valuable starting material to obtain bio-ethanol via fermentation with Saccharomyces cerevisiae. The fermentation of olive-oil milling wastewater has been demonstrated with good yield of ethanol (8-12%v/v) once the level of reducing sugars is appropriate and the phenolic fraction, which inhibits the yeast, is removed. PMID- 17352122 TI - Impact of bioaugmentation with a consortium of bacteria on the remediation of wastewater-containing hydrocarbons. AB - GOALS, SCOPE AND BACKGROUND: It has been observed that hydrocarbon treated wastewaters still contain high COD and a number of intermediates. This suggests that the required catabolic gene pool for further degradation might be absent in the system or, that its titer value is not significant enough. By providing the desired catabolic potential, the overall efficiency of the treatment system can be improved. This study aims to demonstrate this concept by bioaugmentation of a lab-scale reactor treating refinery wastewater with a consortium having the capacity to complement the alkB genotype to the available microbial population. METHODS: Two reactors were set up using activated biomass collected from a refinery treatment plant and operated at a continuous mode for a period of 8 weeks. The feed to both reactors was kept constant. Crude oil was spiked regularly. One reactor was bioaugmented with a consortium previously described for crude oil spill remediation. The efficiency of the bioaugmented reactor was demonstrated by reduced COD. The changes in the microbial population over a period of time were analyzed by RAPD. Catabolic activity of the biomass in both reactors was monitored by PCR. The presence of the catabolic loci was confirmed by Southern Hybridization. RESULTS AND DISCUSSION: 52.2% removal of COD was observed in the bioaugmented reactor while only 15.1% reduction of COD was observed in the reactor without bioaugmentation. The change in microbial population can be seen from the 4th week, which also corresponds to improved catabolic activity. The presence of the bedA locus was seen in all samples, which indicates the presence of aromatic degraders, but the appearance of the alkB locus, from the 6th week onwards, which was observed only in the samples from the bioaugmented reactor. The results suggest that the gene pool of the bioaugmented reactor has catabolic loci that can degrade accumulated intermediates, thus improving the efficiency of the system. CONCLUSIONS: In this study, improvement of efficiency of bioremediation was demonstrated by addition of catabolic loci that are responsible for degradation. Bioaugmentation was carried out in biomass that was collected from an ETP (effluent treatment plant) treating hydrocarbon containing wastewater to study the strategies for improvement of the treatment system. Biostimulation, only marginally improved the efficiency, when compared to bioaugmentation. The improved efficiency was demonstrated by COD removal. The presence of the alkB locus suggests the importance of a catabolic gene pool that acts on accumulated intermediates. It is well documented that straight chain aliphatics and intermediates of aromatic compounds after ring cleavage, accumulate in refinery wastewater systems, thereby hindering further degradation of the wastewater. Supplementation of a catabolic gene pool that treats the lower pathway compounds and alkanes will improve the overall efficiency. In this study, results suggest that the alkB locus can also be used to monitor the degradative mode of the activated biomass. RECOMMENDATIONS AND PERSPECTIVES: Pollution from petroleum and petroleum products around the globe are known to have grave consequences on the environment. Bioremediation, using activated sludge, is one option for the treatment of such wastes. Effluent treatment plants are usually unable to completely degrade the wastewater being treated in the biological unit (the aerator chambers). The efficiency of degradation can be improved by biostimulation and bioaugmentation. This study demonstrates the improved efficiency of a treatment system for wastewater containing hydrocarbons by bioaugmentation of a consortium that supports degradation. Further experiments on a pilot scale are recommended to assess the use of bioaugmentation on a large scale. The use of molecular tools, like DNA probes for alkB, to monitor the system also needs to be explored. PMID- 17352123 TI - Changes in chlorinated organic pollutants and heavy metal content of sediments during pyrolysis. AB - BACKGROUND: There has been an increasing concern about the treatment and disposal of contaminated sediment from dredged rivers, harbors or estuaries due to the accumulated toxic organics such as dioxins and inorganics, particularly heavy metals like Cr, Pb, Zn, Cu, Hg and Cd. However, considering the huge amount of materials and financial costs involved, any candidate technology must ultimately result in reusable, residual by-products. This can only be made possible if the toxic pollutants are removed or stabilized in the raw sediment and then fed back into the materials cycle. Currently, we are developing a pyrolysis process for the commercial-scale cleanup of dioxins and heavy metal-contaminated river sediment to yield reusable char for various economical applications. In this connection, this paper describes our preliminary investigation into the extent of dioxins and heavy metal volatilization from actual contaminated sediment. The stabilization of certain metallic species, particularly Cr ions, was studied. METHODS: Laboratory scale pyrolysis experiments were conducted using a special, horizontal lab-scale pyrolyzer. Sediment samples from Shanghai Suzhou Creek and Tagonoura harbor were pyrolyzed in the reactor under nitrogen gas at 800 degrees C and different retention times of 30, 60 and 90 min. A constant heating rate of 10 degrees C min(-1) was employed. The pyrolysis gas was first allowed to pass through a cold trap to condense the tar. Uncondensed gases were then channeled through a column containing an adsorbent (XAD-2 Resin) for dioxins. Heavy metal concentrations in the initial and final sediment residues were analyzed by ICP (Nippon Jarrel-Ash) following their acid and alkali (for Cr6+) digestion. Dioxin contents of the pyrolysis char, tar, and exhaust gases in the dioxin adsorbent were also determined. For comparative purpose, thermal treatment under air flow was conducted. RESULTS: The data for the removal of heavy metals from Suzhou Creek sediment showed very significant reductions in Pb, Zn and Cr6+ content of the sediment at this condition. Percentage removals were 42.4%, 60.8% and 42.2%, respectively. The disappearance of Cr6+ was due to reduction reactions rather than volatilization, since the total Cr content remained almost unchanged. Other heavy metals such as Cu, Fe and Ni showed very minimal reductions. Nonetheless, Toxicity Characteristics Leaching Procedure (TCLP) tests confirmed that these residual heavy metals were rather stable in the pyrolysis char. Reduction of toxic Cr6+ at 42.2% has also been achieved by pyrolysis (with N2) as opposed to the more than 580% increase in Cr6+ observed during thermal oxidation (with air). DISCUSSION: Pyrolysis also removes toxic organics, particularly dioxins, from the sediment. For the total dioxins, removal percentage of 99.9999% was achieved even at the lowest retention time of 30 min. Almost all polychlorinated dibenzo-p dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs) were removed at any retention time. The TEQs detected from the solid residues were mainly contributed by dioxin-like PCBs, yet these were present in relatively trace quantities. At the shortest retention time of 30 min, only 0.000085 pg-TEQ g(-1) of polychlorinated biphenyls (PCBs) was detected in the pyrolysis char. Furthermore, the residual PCBs have very low toxicity ratings and none of the highly toxic PCBs, which were initially present in the sediment such as 3,3',4,4',5-PeCB and 3,3',4,4'5,5'-HxCB, were detected in the char. Results further confirmed that most of the dioxins that were removed were transferred to the gas phase so that volatilization may be considered as the main mechanism for their removal. CONCLUSION: Some heavy metals, particularly Pb and Zn, can be volatilized under N2 pyrolysis at 800 degrees C. Pyrolysis also prevented the formation of more toxic Cr6+ ions and, at the same time, resulted in its reduction by around 42.2%, in contrast to the 580% increase during thermal oxidation. PCDDs and PCDFs have been removed and were not formed in the solid products over the retention time range of 30-90 min at 800 degrees C. Dioxin-like PCBs mostly remained and a retention time of 30 min was found to be sufficient for its maximum removal. Recommendations and Perspectives. With the above results, a temperature of 800 degrees C at a retention time of 30 min is sufficient for the removal of total dioxins and of some heavy metals by volatilization. It is, however, necessary to destroy the dioxins as well as recover heavy metals in the gas phase. Stability of remaining heavy metals in the char also needs to be confirmed by leaching tests. These are the major concerns, which we are currently evaluating in order to establish the feasibility of our proposed, large scale pyrolysis system for sediment treatment. PMID- 17352124 TI - Ambient air pollution and daily pediatric hospitalizations for asthma. AB - GOAL, SCOPE AND BACKGROUND: A series of severe air pollution episodes in Europe and North America prior to 1960 have focused scientific and regulatory attention on the adverse effects of air pollution on human health. As a consequence of significant reductions in ambient air pollution levels in the intervening years, scientists and public health officials have become more concerned with the potential health effects of exposure to routine concentrations of air pollution. Several recent time series studies conducted worldwide have found relatively low levels of air pollutants that are below national standards were associated with adverse effects on mortality and morbidity. This study examined the effects of ambient air pollution indicators on the daily rate of pediatric hospital admissions for asthma in the Oklahoma City Metropolitan area from 2001-2003. METHODS: Data were collected for the number of children < or = 14 years old hospitalized for asthma on a daily basis (N = 1270) and ambient concentrations of NO2, O3, PM2.5, mold and pollen concentrations, and meso-scale meteorological conditions. Results. Negative binomial regression analysis revealed significant relationships between the total number of hospitalizations per day and the one hour maximum NO2 level, the proportion of susceptible children < 5 years old, and the ratio of temperature to humidity. DISCUSSION: This study of the total number of children aged < or = 14 years old experiencing hospitalizations on a daily basis in the Oklahoma City area from 2001-2003 underscores factors other than ambient air pollution, especially when concentrations are low, affect hospitalizations for pediatric asthma. For example, information related to indoor air quality, health care, family history, and exposure to environmental tobacco smoke and other irritants are not obtainable. Yet, those factors are risk drivers for asthma. Similarly, health privacy requirements prevented obtaining data on physiological factors specific to each child such as differentials in airways functional capacity or other impairments influenced asthma exacerbation. This makes calculating relative risk inappropriate. CONCLUSIONS: Although ambient air pollution concentrations and meteorological conditions influence pediatric asthma hospitalizations, they are not the major predictors in the Oklahoma City metropolitan area. This is consistent with other research that finds limited effects associated with low levels for concentrations of the criteria pollutants. RECOMMENDATIONS AND PERSPECTIVES: Although limiting concentrations for criteria air pollutants to levels below human health-based standards exhibited beneficial effects, other factors also need to be identified and addressed in order to reduce pediatric hospitalizations for asthma. PMID- 17352125 TI - Eco-labelling of shampoos, shower gels and foam baths. AB - GOAL, SCOPE AND BACKGROUND: Environmental issues of personal care products have been met with little attention in the past. Monitoring data as well as preliminary environmental risk assessments indicate that some ingredients in personal care products might be relevant pollutants in the environment. Following the precautionary principle, eco-labelling is proposed as an effective tool for source control of one major group of personal care products, shampoos, shower gels and foam baths (SSBs). Eco-labelling is a soft, but effective market driven and product specific approach to lower discharge of environmentally detrimental substances. Products that fulfil the criteria proposed help to minimise the impact of SSBs on the environment. METHODS: Available assessment tools for dangerous substances (e.g. current legislation on environmental risk assessments and classification, and labelling, eco-labelling criteria for similar products, the calculation of the critical dilution volume) were adapted and integrated into the criteria for the eco-labelling of SSBs. RESULTS AND DISCUSSION: A short outline of the eco-labelling criteria developed for SSBs is provided. The basic criteria concern the effects of the substances discharged into the waste water during and after use. Products with an eco-label award may exclusively contain substances for which basic information about their effects on the environment is available. They may not contain persistent, bioaccumulating, toxic or ecotoxicological substances. In addition, the basic criteria include requirements for the container and consumer information. CONCLUSION: The basic criteria for eco-labelling SSBs are based on the actual state of science and are at the same time as simple and transparent as possible to ensure the best applicability. SSBs that comply with the described basic criteria can contribute to a lower chemical burden of waste water treatment plants and surface water. RECOMMENDATION AND OUTLOOK: The proposal for basic criteria described should stimulate discussion on eco-labelling of SSBs. It should help to pass valid criteria supported by authorities, producers and consumer groups for a national or international eco label, e.g. for the European Flower or the German Blue Angel. In future, the successful introduction of labelled SSBs into the market will raise the awareness of the general public about the environmental effects of personal care products and it will help to promote environmentally compatible products. PMID- 17352126 TI - Effect-directed analysis of key toxicants in European river basins a review. AB - BACKGROUND: Extensive monitoring programs on chemical contamination are run in many European river basins. With respect to the implementation of the European Union (EU) Water Framework Directive (WFD), these programs are increasingly accompanied by monitoring the ecological status of the river basins. Assuming an impact of chemical contamination on the ecological status, the assignment of effects in aquatic ecosystems to those stressors that cause the effects is a prerequisite for taking political or technical measures to achieve the goals of the WFD. Thus, one focus of present European research is on toxicant identification in European river basins in order to allow for a reduction of toxic pressure on aquatic ecosystems according to the WFD. MAIN FEATURES: An overview is presented on studies that were performed to link chemical pollution in European river basins to measurable ecotoxic effects. This includes correlation-based approaches as well as investigations that apply effect-directed analysis (EDA) integrating toxicity testing, fractionation and non-target chemical analysis. Effect-based key toxicants that were identified in European surface waters are compiled and compared to EU priority pollutants. Further needs for research are identified. RESULTS: Studies on the identification of effect based key toxicants focused on mutagenicity, aryl hydrocarbon receptor-mediated effects, endocrine disruption, green algae, and invertebrates. The identified pollutants include priority pollutants and other well-known environmental pollutants such as polycyclic aromatic hydrocarbons, polychlorinated dibenzo-p dioxins, furans, and biphenyls, nonylphenol, some pesticides and tributyltin, but also other compounds that were neither considered as environmental pollutants before nor regulated such as substituted phenols, natural or synthetic estrogens and androgens, dinaphthofurans, 2-(2-naphthalenyl)benzothiophene, and N-phenyl-2 naphthylamine. DISCUSSION: Individual studies at specific sites in a European river basin demonstrated the power of combined biological and chemical analytical approaches and, particularly, of effect-directed analysis. However, the available information on effect-based key toxicants is very limited with respect to the entirety of rivers possibly at risk due to chemical contamination and with respect to toxicological endpoints considered at a specific site. A relatively broad basis of information exists only for estrogenicity and aryl hydrocarbon Ah receptor-mediated effects. CONCLUSIONS: The development of tools and strategies for an identification of key toxicants on a broader scale are a challenging task for the next years. Since investigations dealing with toxicant identification are too labor and cost-intensive for monitoring purposes, they have to be focused on the key sites in a river basin. These should include hot spots of contamination, particularly if there is evidence that they might pose a risk for downstream areas, but may also involve accumulation zones in the lower reach of a river in order to get an integrated picture on the contamination of the basin. Recommendations and Perspectives. While EDA is almost exclusively based on measurable effects in in vitro and in vivo biotests to date, an increasing focus in the future should be on the integration of EDA into Ecological Risk Assessment and on the development of tools to confirm EDA-determined key toxicants as stressors in populations, communities and ecosystems. Considering these requirements and applied in a focused way, toxicant identification may significantly help to implement the Water Framework Directive by providing evidence on the main stressors and possible mitigation measures in order to improve the ecological status of a river ecosystem. PMID- 17352127 TI - Japanese whaling and other cetacean fisheries. AB - BACKGROUND, AIM AND SCOPE: Discussions on management of whales and whaling are factually monopolized by the International Whaling Commission (IWC), resulting in a limitation of information flow to outside communities. With an aim to improve the situation, this article briefly reviews whaling and dolphin/porpoise fisheries in Japan, which is recognized to be the world largest cetacean exploitation. MAIN FEATURES: The Japanese government grants an annual take of 22,647 cetaceans of 15 species for scientific whaling and various kinds of active dolphin/porpoise fisheries by the nationals. Further, over 100 baleen whales and numerous small cetaceans are taken in passive net fisheries. They are used mostly for human consumption and some for aquarium display. RESULTS: Sustainability of the take is not evident and some populations have shown a historical decline. The Japanese program of scientific whaling has been reviewed by IWC and its Scientific Committee (SC), although they have arrived at no consensus. DISCUSSION: The current scientific whaling program invites arguments from the view points of science as well as concerning the ethics of scientists, economy, and interpretation of the International Convention for Regulation of Whaling (ICRW) of 1946. The scientific whaling and other Japanese cetacean fisheries are benefited from nationalistic public attitude, and ambiguity and weakness of the ICRW. CONCLUSIONS: Japanese cetacean harvest will continue supported by domestic demand for whale products as long as the proceeds can sustain the operation, even with criticisms from outside communities. RECOMMENDATIONS AND PERSPECTIVES: For safe management of small cetaceans exploited by Japan, studies are urgent on the population structure, abundance and validity of catch statistics. The results should be open to scientific communities. PMID- 17352129 TI - Reclaiming the definition of sustainability. AB - BACKGROUND AND SCOPE: Since its inception two decades ago, the concept of sustainable development has suffered from a proliferation of definitions, such that it has increasingly come to mean many things to many different people. This has limited its credibility, called into question its practical application and the significance of associated achievements and, overall, limited the progress in environmental and social developments which it was designed to underpin. GOAL: This viewpoint article is intended to re-open the concept of sustainable development for discussion 20 years on from the Brundtland Report, in the context of the current state of the world, our growing understanding of ecosystems and their response to stressors and the parallel increase in recognition of inherent limitations to that understanding. APPROACH: Following a brief review of the diverse manner in which the concept has developed over time, we present the case for application of a series of simple conditions for sustainability, originally developed by The Natural Step in the early 90s, which nevertheless still provide a sound basis on which progress towards sustainable development could be monitored. The paper also highlights the unavoidable links between sustainability and ethics, including those in the sensitive fields of population and quality of life. DISCUSSION: Overall we argue the need for the concept of sustainable development to be reclaimed from the plethora of economically-focused or somewhat vague and un-measurable definitions which have found increasing favour in recent years and which all too often accompany relatively minor progress against 'business as usual'. RECOMMENDATIONS AND PERSPECTIVES: The vision encapsulated in the Brundtland Report was ground-breaking. If, however, true sustainability in human interactions with the biosphere is to be realised, a far stronger and more empirical interpretation of the original intent is urgently required. To be effective, such an interpretation must encompass and guide developments in political instruments and public policy as well as corporate decision-making, and must focus increasingly on addressing the root causes of major threats to sustainability rather than just their consequences. PMID- 17352128 TI - Identification of pollution source of cadmium in soil: application of material flow analysis and a case study in Taiwan. AB - BACKGROUND: Since the 1970s, at least 200 hectares (ha) of farm-land has been polluted by the heavy metal cadmium (Cd). Consequently, the Cd pollution has led to contaminate the rice production and caused acute social panic. According to the recent investigation results performed by the Taiwan Environmental Protection Administration (TEPA), it is indicated that most of the Cd pollution incidents in Taiwan resulted from the waste-water discharge of stearate Cd factories. To prevent the Cd pollution incidents from spreading, the TEPA has either forced these factories to close down or assisted them in improving their production processes since the 1980s. Unfortunately, accidental incidents of Cd pollution still emerge in an endless stream, despite the strict governmental controls placed on these questionable factories. Whether this pollution has resulted from undetected or hidden pollution sources stemming from two decades ago or comes from some new source, will be an outstanding issue. Therefore, this study attempts to identify the pollution sources of Cd in soil in Taiwan as well as to find the solution to the above-mentioned, outstanding issue by way of a methodology termed Material Flow Analysis (MFA). METHODOLOGY: The MFA has proved to be a useful tool on providing quantitative information of the flow of substances through an economic to an environmental system. Based upon the supply and-demand theory of MFA, researchers have successfully conducted an overview of the use of materials in many industries, the construction industry being one of these. Therefore, this study tries to establish a set of analytical processes by way of MFA for identifying the pollution source of Cd in soil in Taiwan. In addition, the spirit of Life Cycle Assessment (LCA) technique was also employed to identify the materials, and products should be ignored as a crucial pollution source in this study. RESULTS AND DISCUSSION: According to the MFA methodology applied in this study and on the basis of related studies performed by Taiwanese governmental authorities, we arrive at the following analysis results: (1) the total amount of Cd from the economic perspective of material and product flow was approximately 441.2 tons; (2) the wastewater directly discharged into irrigation water can be concluded to be the major pollution route of Cd in farmland soil in Taiwan; (3) material plastic stabilizer (cadmium oxide, CdO), Zn-Pd compounds and Cu compounds should be the crucial pollution sources to contaminate environment through the route of wastewater in Cd flow analysis; (4) the crucial pollution sources to contaminate environment through the route of wastewater in Cd flow analysis were five factories, Coin, Jili, Taiwan Dye, Guangzheng and Mingguan, and they were all categorized as stearate Cd industries; (5) the typical source of the Cd pollution in soil in Changhua County through the pollution route of wastewater should be the metal surfacing process industries. CONCLUSIONS: This study proved that MFA can be a good tool for identifying Cd flow as well as for recognizing the crux of the problem concerning incidents of Cd pollution. This study led to the conclusion that the causal relationship between farmland pollution caused by Cd and stearate Cd factories in Taiwan seemed quite close by way of MFA methodology. In addition, this study also found that the wastewater discharged from a single metal surfacing process factory will not cause remarkable farmland pollution. However, the wastewater simultaneously discharged from a group of pollution factories can result in a significant pollution incident. RECOMMENDATIONS AND OUTLOOK: This case study is only a small contribution to the understanding of the toxic material flow related to Cd in the environment. This study recommends that Taiwanese governmental authorities should not deal with problems on an ad hoc basis, but should instead deal with Cd pollution problems overall employing control measures. Finally, the more accurate information or data we can collect, the more reliable results we can identify. Therefore, the quality and quantity of related data used in this MFA model should be closely scrutinized in order to ensure the most correct and comprehensive investigation on the toxic material flow. PMID- 17352130 TI - Biogas: can it be an important source of energy? PMID- 17352131 TI - 26th International Symposium on Halogenated Environmental Organic Pollutants and POPs (Dioxin 2006). PMID- 17352132 TI - [Therapeutic strategy for spontaneous pneumothorax]. AB - This study assesed the treatment of spontaneous pneumothorax from April 1998 to October 2004. Chest computed tomography (CT) was conducted on admission to judge the presence or absence of bulla and/or bleb. A total of 168 cases (112 patients) were treated. There were 93 men and 19 women with a mean age of 40.6 (range, 15 to 98) years. Of the total cases, 119 were the first pneumothorax, and 49 cases were recurrence. Video-assisted thoracoscopic surgery (VATS) was the first-choice surgical procedure. We compared a retrospective series of 168 cases treated by observation with chest tube drainage in 94 cases and bed rest in 3 cases (57.7%), VATS in 62 cases (36.9%), or limited thoracotomy (LT) conventionally in 9 cases (5.4%). The recurrence rate by observation, VATS, or LT was 42, 13, and 0%, respectively. The rate of recurrence in the observation group was higher than in the VATS group, and the rate of recurrence in the presence of bulla and/or bleb was 48% and that of recurrence in their absence was 20%. These results suggest that VATS or LT should be recommended for patients with bulla and/or bleb indicated by chest CT. In VATS, an auto-sutured line with a polyglycolic acid (PGA) sheet and the use of fibrin glue spray were thought to be effective in preventing the recurrence of pneumothorax. Futhermore, LT with primary suturing was thought to be useful in cases of skip and multiple, in consideration of the numbers, patterns, and properties of the bulla and/or bleb from the intraoperative findings through the thoracoscope. PMID- 17352133 TI - [Coronary revascularization in patients with preoperative electrical storm]. AB - We report 5 cases who underwent surgical coronary revascularization for subacute myocardial ischemia with preoperative electrical storm. All patients showed severe left ventricular dysfunction. Mean ejection fraction was 24.4 +/- 7.6%. Three patients had already had implantable cardioverter-defibrillator (ICD) therapy. Procedures were on-pump coronary artery bypass grafting (CABG) and mitral valvuloplasty (MVP) [case 1], on-pump CABG, MVP, left ventricular restoration (LVR) and cryoablation (case 2), and off-pump CABG (case 3-5). Case 5 necessitated conversion to on-pump for electrical storm during left circumflex artery (LCx) anastomosis. Case 3 suddenly died on the 2nd postoperative day due to electrical storm. Case 1 had recurrent attack of electrical storm postoperatively, treated by ICD, overdrive pacing, repeated intraaortic balloon pumping (IABP), deep sedation with endotracheal intubation, and finally catheter ablation. Four patients have survived 2 years (mean) postoperatively without any arrhythmia, and are all in good condition [New York Heart Association (NYHA) I] now. It was concluded that off-pump procedure was not suitable for subacute myocardial ischemia with electrical storm and that LVR with surgical cryoablation would be effective if indicated. PMID- 17352134 TI - [Thymoma transformed to thymic carcinoma with brain and bone metastases 6 years after recurrence]. AB - We report a man who developed brain and bone metastases 6 years after resection of recurrent thymoma. The patient underwent surgery for B2-thymoma [World Health Organization (WHO) classification] without microscopic capsular invasion at 50 year-old. The next year, he underwent the second surgery for recurrent B2-thymoma as pleural dissemination. Seven months after the second surgery, he developed recurrence of pleural dissemination. The patient refused any further aggressive treatment, including surgery, chemotherapy, and radiotherapy. The pleural disease did not increase over 6 years, then suddenly enlarged. Thereafter, the patient developed left hemiparesis due to brain metastases, followed by bone metastases. Immunochemical studies of the metastatic tumors demonstrated that these lesions seemed to be poorly differentiated thymic carcinoma (small cell carcinoma) on WHO classification. We concluded that the thymoma transformed to thymic carcinoma with brain and bone metastases during 6 years. PMID- 17352135 TI - [Left circumflex coronary aneurysm with separated left main trunk]. AB - We report a left circumflex coronary aneurysm associated with separated left main coronary trunks (LMT). A 66-year-old man was admitted to our hospital for further examination of dyspnea on effort. He has been performed maintenance hemodialysis since 1999 for chronic renal failure. Coronary angiography and multislice spiral computed tomography (CT) revealed an unusual coronary anatomic variance in which separate origins of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries arose from the left coronary aortic sinus. Furthermore, these images of the LCx revealed an aneurysm 2 cm in diameter and 99% stenosis at the proximal of side of the aneurysm. Under cardioplegic arrest, the aneurysm was ligated and coronary artery bypass grafting (left thoracic artery to posterolateral branch) was performed. The patient was discharged at the 20th postoperative day without any complication. PMID- 17352136 TI - [Extraabdominal desmoid tumor of the chest wall]. AB - We report a rare case of desmoid tumor of the chest wall. A 75-year-old female visited our hospital due to a feeling of oppression in the left chest. A chest X ray, computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large mass in the left thorax. Surgical resection of the tumor was performed under the left standard thoracotomy. The tumor was 90 x 80 x 75 mm in size and diagnosed pathologically as desmoid tumor which showed proliferation of spindle shape cells and collagen fibers. Immunohistochemistry revealed that the tumor cells were positive for vimentin, alpha-smooth muscle actin and negative for CD34. The patient has been well without recurrence for 2 years and 2 months after surgery. PMID- 17352137 TI - [Video-assisted thoracoscopic lobectomy for lung cancer patients with severe incomplete fissures or emphysema; intralobar no-touch access technique (INTACT)]. AB - OBJECTIVES: Severe air leak after lobectomy is one of well-known complications in lung cancer patients with severe emphysema or incomplete fissure. A developing air leak or persistent air leak in those patients may occur postoperative pneumonia or empyema. MATERIALS AND METHODS: For those patients, we have operated with intralobar no-touch access technique (INTACT) assisted with thoracoscopy. INTACT is a surgical procedure of lobectomy without interlobar access, a procedure of prior dissection of lobar bronchus and stapling all the fissure. From January 2004 to December 2005, we performed surgery in 227 patients with primary lung cancer, and 12 patients were performed with lobectmy with INTACT among them. Mean age was 68 +/- 7 years. RESULTS: Distribution of lobectomies was as follows: right upper lobe, 7 patients; right upper lobe and S6 segment, 1; right middle lobe and right lower lobe, 1; left upper lobe, 2; left lower lobe, 1. The length of major skin incision was 5-15 (average 9.2 +/- 3.0) cm. Pathological stage were IA in 3 patients, IB in 7, IIIA in 1 and IIIB in 1. The backgrounds of those patients were severely emphysema in 7 patients, incomplete fissure in 2, both emphysema and incomplete fissure in 2 and emphysema and huge sized tumor in 1. The postoperative air leak stopped 1.8 +/- 0.8 days. CONCLUSIONS: For carefully selected patients video-assisted thoracoscopic lobectomy by INTACT for lung cancer patients with emphysema or incomplete fissure could be a safe and valuable procedure. PMID- 17352138 TI - [Dissection of descending aorta with spinal paralysis]. AB - A 56-year-old man had undergone ascending aorta and total arch replacement because of aortic dissection (Stanford type A) in 1997. He had onset of diplegia of the lower limb and vesicorectal disability. Computed tomography (CT) showed serpentine aneurysm in the descending aorta, it was seen between the left subclavian artery and diaphragm level. It was 80 mm of maximum diameter. Magnetic resonance imaging (MRI) was performed for identified Adamkiewicz artery, but we could not identify it. We performed a graft replacement. The 8th intercostal artery was reconstructed with a branch graft. The postoperative course was uneventful. We conclude that graft replacement for spinal ischemia can be effective. PMID- 17352139 TI - [Left ventricular-right atrial communication resulting from infective endocarditis]. AB - We report a rare case of acquired left ventricular-right atrial communication resulting from infective endocarditis. A 57-year-old male with aortic regurgitation due to infective endocarditis was referred to our hospital because of severe congestive heart failure. Preoperative transthoracic echocardiography showed aortic, mitral and tricuspid severe regurgitations. Intraoperative transesophageal echocardiography revealed left ventricular-right atrial shunt. The fistula was located at the atrioventricular membranous septum. The communication site from the left view was below the commissure between the right coronary cusp and non-coronary cusp, and from the right view was just above the tricuspid annulus of the septal leaflet. The fistula was closed directly with mattress suture and aortic valve replacement and both mitral and tricuspid ring annuloplasty were carried out simultaneously. The postoperative course was uneventful. It is important to inspect shunts carefully in echocardiography of infective endocarditis with massive regurgitations. PMID- 17352140 TI - [Bilateral coronary-pulmonary artery fistulae without cardiopulmonary bypass]. AB - A 68-year-old female with heart failure was admitted on the probable diagnosis of patent ductus arteriosus. Coronary arteriography revealed the coronary-pulmonary artery fistulae which originated the bilateral coronary arteries. Excision of coronary artery fistulae was performed without cardiopulmonary bypass. The symptom of heart failure has been improved for postoperative 6 years. Coronary pulmonary artery fistula is commonly a meanders long and flowing into the pulmonary artery as one influx artery. We presume the surgical intervention without cardiopulmonary bypass would be adopted for the treatment of this type. Multidetector-row computed tomography (MD CT) is useful in verification to detect the perioperative fistulae. PMID- 17352141 TI - [Long-term survival of malignant fibrous histiocytoma of the chest wall by multidisciplinary treatment]. AB - We report a case of malignant fibrous histiocytoma (MFH) of the chest wall. A 70 year-old man admitted for recurrent chest wall tumor diagnosed for MFH histologically and resected 7 months and 13 months before admission. Chest computed tomography (CT) revealed a tumor located at right posterior chest wall. In May 1997, resection of the tumor was done (the 3rd operation), but metastasis to the ribs (the 4th operation), subcutaneous tissue (the 5th operation), and local recurrence (the 6th operation) was found within 4 years postoperatively. Resection was done for each metastasis, and postoperative radiotherapy (66 Gy) and chemotherapy (CYVADIC) were done. The patient is doing well without apparent recurrence 57 months after last surgery, and survives 113 months after initial surgery. Multidisciplinary treatment may provide longer survival for patients with MFH of the chest wall. PMID- 17352142 TI - [Left atrial myxoma surgically resected in acute phase of hemorrhagic cerebral infarction; report of a case]. AB - A 61-year-old man who had been suffered from several episodes of cerebral infarction for 3 years complained of left-sided paresthesia and was pointed out hemorrhagic infarction in the right frontal area of the brain by computed tomography (CT) and magnetic resonance imaging (MRI). The echocardiography showed left atrial mass 9 cm in length attaching to the atrial septum, which was diagnosed as left atrial myxoma causing cerebral embolism. As serial MRI showed frequent episode of cerebral infarction, we performed surgical resection of the cardiac tumor on the 10th day after the onset of the neurological symptom. Anticoagulation during cardiopulmonary bypass was maintained with 1.5 mg/kg of heparin sodium and 80 mg/hour of nafamostat mesilate (FUT). Postoperative course was uneventful without neurological deterioration. PMID- 17352143 TI - [Mitral valve replacement for hypertrophic obstructive cardiomyopathy with repeated heart failure; report of a case]. AB - A 62-year-old woman with hypertrophic obstructive cardiomyopathy suffered from repeated heart failure. Preoperative echocardiogrphy demonstrated pressure gradient (PG) of 64 mmHg in left ventricular cavity, mitral regurgitation II, and tricuspid regurgitation II with an ejection fraction of 74%. Cardiac catheterizaition revealed cardiac index of 1.50 l/min/m2. She was recommended mitral valve replacement (MVR) because she was hospitalized several times for heart failure. She underwent MVR, tricuspid annuloplasty, and modified maze operation. Postoperative PG fell till 15 mmHg in echocardiogrphy. Postoperative cardiac catheterization revealed cardiac index of 2.00 l/min/m2. MVR contributed to decrease of PG in intraventricular cavity and increase of cardiac output. Postoperative cardiac status was classified as New York Heart Association (NYHA) class I-II. PMID- 17352144 TI - [Tricuspid valve replacement for elderly patients with isolated tricuspid valve regurgitation; report of 2 cases]. AB - Isolated tricuspid valve regurgitation (TR) is a rare clinical entity. We report 2 patients, 80 and 74-year-old with isolated TR. They underwent valve replacement with the Carpentier-Edwards bioprosthesis because of resistance to medical treatment. The causes of insufficiency were suspected as congenital in case 1 and infective endocarditis in case 2, respectively. Postoperative course was free from major complications in both patients. Valvuloplasty and/or annuloplasty are recommended for TR, however, replacement of the tricuspid valve is sometimes necessary in isolated TR patients. The higher occurrence of thrombosis of mechanical prosthesis in the tricuspid position has been reported. The bioprosthesis in tricuspid position may reduce the rate of thromboembolism, thrombosis and structural dysfunction, therefore it may be an option for radical therapy in isolated TR especially in aged patients. PMID- 17352145 TI - [Pneumonectomy for lung cancer in a patient with acute respiratory failure; report of a case]. AB - A 58-year-old man had developed acute respiratory failure because of deterioration of the pneumonia, and had been on a mechanical ventilator. Bronchoscopy showed tumor occlusion of the left main stem of the bronchus. For the purpose of weaning from ventilatory support and prevention of progress of the pneumonia, we performed a pneumonectomy and systematic hilar and mediastinal lymph node dissection using a thoracoscopy. The patient could be weaned from ventilatory support, and we could improve his quality of life by minimally invasive surgery. PMID- 17352146 TI - [Pulmonary pleomorphic carcinoma with rapid and peculiar metastases; report of a case]. AB - A 54-year-old man was pointed out a mass shadow during treatment of suspected acute pyothorax. He was diagnosed as large cell carcinoma by transbronchial biopsy. Preoperative chemotherapy and right lower lobectomy were done. In pathological examination, he was diagnosed as pulmonary pleomorpic carcinoma. Postoperatively, he had rapid metastases of the pancreas, skin, muscle, brain and oral cavity. We reported a case of pulmonary pleomorphic carcinoma with rapid and peculiar metastases. PMID- 17352147 TI - [Adult growth hormone deficiency: its etiology, pathophysiology, diagnosis, and treatment]. PMID- 17352148 TI - [Selective anterior clinoidectomy]. PMID- 17352150 TI - [The influence of the primary management on the outcome of severe traumatic brain injury: role of neurosurgeons]. AB - OBJECTIVE: To evaluate the influence of the primary management on the outcome in severe head-injured-patients, we retrospectively studied the patients transported to our hospital directly and the those referred from other hospitals. METHODS: The subjects include 83 patients with severe head injury with a Glasgow coma scale (GCS) score of 8 or lower at the time of arrival at the emergency room during the periods of between January, 2003 to March, 2006. Forty nine patients were transported directly (direct group) and 34 referred from other hospitals (transfer group). The patients in direct group was transported by a helicopter or an ambulance car, and the patients in transfer group were carried by an ambulance car. The variables analyzed in these 2 groups of patients were the initial GCS score, injury severity score (ISS), and the presence or absence of light reflex or shock at the time of transportation, the time periods from the injury and primary management, the time from the injury and operation in surgical patients, the type of primary managements and outcomes. RESULT: The number of patients with shock was significantly larger in the transfer group than that in the direct group. The shock was considered to be developed during the transportation. The outcomes were then significantly poorer in the transfer group than those in the direct group. There was no significant difference between the time from the injury and primary management in these 2 groups, but the primary management seemed to be more appropriate in the direct group compared to that in the transfer group. These findings suggested that outcomes of severe high-impact head injuries, such as injuries caused by a traffic accident, would be markedly affected by the primary treatment. CONCLUSION: The doctor-helicopter system, in which emergency physicians arrive at the site shortly after the occurrence of injury, and start primary examination, will influence outcomes of multiple injuries accompanying severe head injury. Severe head-injured patients by high impact injury should be transported as early as possible to the emergency medical center, and neurosurgeons have an important role in the primary management. PMID- 17352151 TI - [Novel 3D MR angiographic findings of neurovascular compressive sites in patients with trigeminal neuralgia]. AB - Neurovascular compressive sites at the root entry zone of the trigeminal nerve were investigated in 25 patients with trigeminal neuralgia by using the fine three-dimensional (3D) magnetic resonance (MR) angiogram, obtained by a 3D time of-flight, spoiled gradient-recalled sequence. The characteristic 3D MR angiographic findings of the offending vessels were obtained at the neurovascular compressive sites 19/23 (83%), including intermittent MR signal intensity within the vessels in 14/23 (61%), and unclear margin of the vessels in 5/23 (22%). Those abnormal 3D MR angiographic findings were commonly observed at the site of neurovascular compression in conjunction with moderate degree (grade II) and severe degree (grade III) in 19/20 (95%) of the actual nerve compression by the offending vessels. Abnormal findings with 3D MR angiograms may provide flow related information to suggest a certain neurovascular compression upon the trigeminal nerve by the offending vessels. Those novel 3D MR angiographic findings may be useful for the diagnosis and decision-making process to execute the microvascular decompression surgery in patients with trigeminal neuralgia. PMID- 17352152 TI - [An aneurysm located at a fenestration of the vertebrobasilar junction successfully treated with Guglielmi detachable coils]. AB - A 35-year-old female developed a subarachnoid hemorrhage from an aneurysm located at the fenestration of the vertebrobasilar (VB) junction. The patient was treated with Guglielmi detachable coils (GDCs). The aneurysm was successfully occluded using 8 coils despite the fact that 2 major complications occurred during the procedure: perforation of the aneurysm with a coil and thrombosis of the parent artery. The GDC that had perforated the aneurysm was left and remained partially in the subarachnoid space, and embolization was continued. The thrombus was mechanically crushed and dissolved. Forty days postoperatively, the patient was discharged home with minimal sequelae. VB junction fenestration is present in 35.5%-70% of VB junction aneurysms, but fenestration of the VB junction is sometimes overlooked on selective angiography. Careful pre-operative assessment is needed for aneurysms at the VB junction. The international subarachnoid aneurysm trial (ISAT) found that endovascular treatment was superior to surgery in the management of ruptured aneurysms. Nevertheless, thromboembolic complications and perforation are associated with coil embolization. Thus, care should be taken to avoid these complications, and it is indispensable to have appropriate treatment options immediately available to deal with them should they occur. PMID- 17352153 TI - [Intracranial osteolytic hemangiopericytoma manifesting as a rapidly enlarging extracranial soft tissue mass lesion]. AB - Hemangiopericytoma is a highly vascular and rapidly growing tumor, which tends to recur at distant locations. Complete surgical resection is often difficult because of intraoperative excessive hemorrhage or brain swelling. A 31-year-old male presented with intracranial osteolytic hemangiopericytoma manifesting as a rapidly enlarging extracranial soft tissue mass lesion causing a subcutaneous mass in the forehead. Computed tomography (CT) and magnetic resonance (MR) imaging demonstrated a lesion in the frontal lobe. Careful follow up was performed because the patient suffered no neurological deficits. The subcutaneous mass rapidly enlarged for 6 months. CT and MR imaging showed an osteolytic intracalvarial lesion with an extradural soft tissue component. Angiography demonstrated obstruction of the superior sagittal sinus and dense tumor staining with slow circulation and venous drainage. Gross total surgical resection was performed following endovascular embolization of the feeding arteries. Histological examination demonstrated an hemangiopericytoma. Although rare, hemangiopericytoma should be included in the differential diagnosis of rapidly enlarging subcutaneous mass. Preoperative endovascular treatment may allow less invasive surgery. PMID- 17352154 TI - [Artery-to-artery embolism due to ruptured calcified carotid plaque]. AB - Calcified carotid plaques are thought to be less likely to be symptomatic than non-calcified plaques. We present a patient with an unusual cerebral embolism that appeared as very high density on CT and was ascertained to derive from a calcified plaque. This 46-year-old male was admitted within 1 hr of sudden aphasia onset. The admission CT scan showed multiple high-intensity lesions that appeared like calcification. They were high intensity on MRI FLAIR images. MRA showed occlusion of the posterior trunk of the middle cerebral artery. As we considered cerebral embolism, the patient received heparin followed by warfarin. Routine MRA and DSA detected no abnormality, however, a carotid echogram showed a hyperechoic plaque at the left carotid bifurcation. As the NASCET method indicated 6.5% stenosis, carotid endarterectomy was not indicated. However, the thrombus at the bifurcation gradually enlarged despite adequate medical treatment (PT-INR 2.2 - 2.7) and we decided to surgically remove the calcified plaque, thought to be the embolus source. We removed the plaque content through a defect in the plaque membrane. Intraoperatively we found that the rapidly enlarging lesion was the plaque content rather than a thrombus. Pathologically, calcification was more dominant than atherosclerosis. His postoperative course was good and he required only aspirin. This case was peculiar in that the calcification mimicked a hyperdensity embolus and that the lesion derived from a calcified plaque which is usually stable. Repeat carotid ultrasonography is easy and useful when routine investigation fails to reveal the embolic source. PMID- 17352155 TI - [New diagnostic imaging methods in neurosurgery: advent of anatomical and functional neuroimaging]. AB - Progress in imaging techniques has contributed to improvements in reliable diagnosis and surgical decision making in neurosurgery. From the viewpoint of neurosurgeons, there are two major needs in the development of imaging techniques. One is greater accuracy in demonstrating the anatomy of the brain at microscopic resolutions and the other is visualization of function or metabolism that is invisible on surgical views. Use of 3.0 T magnetic resonance imaging (MRI) in clinical patients has revealed anatomy appropriate for microsurgery at high resolution, and three-dimensional reconstruction of MRI on high specification computers helps neurosurgeons to understand the anatomy of the brain in individual patients. Functional imaging methods such as functional MRI, positron emission tomography, and magnetoencephalography have provided new insights in brain surgery, visualizing various cerebral functions on anatomic images. Recently, diffusion tensor imaging is used to visualize neural tracts passing through subcortical white matter and MR spectroscopy is used to show the metabolic status of lesions. These tools are also forms of functional imaging. New noninvasive imaging techniques are still being developed to visualize function more easily. Here, we summarize the roles of recent imaging techniques in our previous studies and discuss the future of imaging in neurosurgery. PMID- 17352156 TI - [Clinical investigation of infertile males with chromosomal anomalies]. AB - A chromosomal survey using the G-banding technique was performed on 87 subfertile male whose semen analysis demonstrated severe oligospermia and azoospermia at Yokohama City University Hospital between January 1990 and October 2002. Fourteen of these subjects demonstrated major chromosomal anomalies (16.1%). Semen analysis in these cases demonstrated azoospermia, except in one case of autosomal abnormality. Twelve patients showed sex chromosomal abnormalities including 8 Klinefelter syndrome (47XXY) and 2 XX males (46XX) and two patients had autosomal abnormalities. The follicle-stimulating hormone (FSH) value in these patients, except for the two cases of autosomal abnormality and one case of 46XYq-, was much higher than normal. Histological examination was performed in 7 cases. In these cases, intratesticular spermatozoa were seen in only two cases (Klinefelter syndrome case and ring chromosome 21 case). Chromosome studies are important in the evaluation of subfertile patients with azoospermia and severe oligospermia. Because the abnormal genotype could be transferred to the next generation, the importance of chromosome studies before ICSI should be emphasized. PMID- 17352157 TI - The preliminary results of docetaxel-prednisolone combination therapy for the Japanese patients with hormone-refractory prostate cancer. AB - Between April 2004 and August 2005, we used docetaxel in combination with prednisolone to treat 14 patients with hormone-refractory prostate cancer (HRPC). Docetaxel was administered at a dose of 70 mg/m2 once every 21 days and oral prednisolone 5 mg was administered twice daily concurrently on days 1-21. The treatment was continued until disease progression or unacceptable adverse events occurred. Prostate specific antigen (PSA) was used as a tumor marker. PSA response was defined as a reduction from baseline of at least 50% that was maintained for 4 weeks. Five patients had measurable soft tissue lesions, which were nodal metastases in 4 and liver metastasis in 1. The median follow-up was 8.4 months. During follow-up, 5 patients died. The median treatment cycle was 7 cycles. Manifestations of hematologic toxicity included 11 patients (78%) with grade 3/4 neutropenia and only I with febrile neutropenia. Two patients with gastric hemorrhage and febrile neutropenia needed hospitalization. During follow up, 8 patients (57%) achieved a PSA reduction from baseline of at least 50%. Three patients with nodal metastases and 1 patient with liver metastasis had partial response. Combined docetaxel and prednisolone was shown to be effective and feasible in Japanese patients. PMID- 17352158 TI - Oral estramustine phosphate and oral etoposide for the treatment of hormone refractory prostate cancer. AB - A total of 42 patients with hormone-refractory prostate cancer received E-E therapy. Oral estramustine phosphate (EMP) was administered twice daily for a total daily dose of 560 mg every day and oral etoposide (E-E therapy, 50 mg/body/day) was given on days 1-21 and stopped on days 22-35. Treatment was continued until the disease progression was confirmed radiographically or PSA had increased from base line of at least 25%. The median follow-up period after E-E therapy was 77.4 months (range : 12.5 to 122.3). Nineteen patients (43%) achieved a PSA decrease of 50% or greater. The median survival time of the patients who had a decrease of 50% or greater in the PSA value (PSA responder) was 29.3 months and the patients who did not (PSA non-responder) was 14.1 months (p = 0.01). There were no significant differences between PSA responders and non-responders when taking into account variables. Excluding those patients with only PSA elevation, the survival time was 14.9 months with no significant difference between PSA responders and non-responders. The toxicities (grade 3 or more) were identified as anemia, leukocytopenia thrombocytopenia, cardiovascular events, and gastrointestinal and hepatic disorders, which occurred in 0, 5, 2, 2, 14, and 2% of the patients, respectively. E-E therapy was considered to be an active oral regimen and well-tolerated for outpatients with hormone-refractory prostate cancer in Japanese patients. PMID- 17352159 TI - [Adrenal pseudocyst; a case report]. AB - We report a case of adrenal pseudocyst. A 35-year-old woman presented with palpation of right upper abdominal mass without tenderness. Abdominal computed tomographic scan showed a right retroperitoneal cystic mass 20 cm in diameter. The patient underwent complete resection of the mass, including the normal adrenal gland. The cyst contained 3100 ml of dark brown thrombotic liquid. Histopathological examination revealed adrenal pseudocyst with a thick figrocollagenous wall. The normal adrenal gland was compressed by the wall. Adrenal pseudocyst is a rare disease. The mechanisms of adrenal pseudocyst formation and their expanding nature are discussed. PMID- 17352160 TI - [Clinical evaluation of our first 50 laparoscopic adrenalectomies]. AB - We performed 50 laparoscopic adrenalectomies during the period from 1998 through 2003. We report our experience and the outcomes of this procedure, which has become a standard surgery for adrenal tumors. In most cases, the transperitoneal approach was used. In 48 cases, laparoscopic adrenalectomy was performed successfully. However, in two cases, the operation was converted to an open procedure because of bleeding. As our experience with laparoscopic adrenalectomy increased, operation time decreased. Laparoscopic adrenalectomy should be used more widely in the future. PMID- 17352161 TI - [Renal lymphangioma: report of a case]. AB - Renal lymphangioma is a very rare benign tumor caused by failure in the development of the lymphatic communication system. Since December 1997, a 55-year old man with chronic B-type virus hepatitis has been followed at our hospital. Neither kidney showed any sign of cysts at that time. In November 2000, ultrasound sonography showed a right renal simple cyst measuring 1.0 cm in diameter. Thereafter, the initial cyst increased to 5.5 cm and numerous right renal cysts, appearing similar to multilocular renal cysts, were detected in December 2004. Computed tomography demonstrated a right renal multilocular cystic tumor, 5.5 cm in diameter, which was enhanced by contrast medium. Radical nephrectomy was performed, and the pathological diagnosis was renal lymphangioma based on positive staining with D2-40 antibody, which is reactive to endothelial cells of the lymphatics. PMID- 17352162 TI - [Bilateral renal cell carcinoma associated with polycystic kidney disease: case report and literature review]. AB - A 56-year-old Japanese man consulted a urologist because of urethral bleeding. He had been undergoing hemodialysis for the past 15 years due to polycystic kidney disease. Computed tomography revealed an irregular cyst wall in the left kidney. Since a neoplasm could not be ruled out, we removed the left kidney, by laparoscopic radical nephrectomy after obtaining the patient's consent. Histopathologic diagnosis was renal cell carcinoma. Fourteen months after the operation, urethral bleeding recurred. Further examination of the bladder and the urethra revealed no significant abnormalities. The patient insisted on right nephrectomy. Therefore, laparoscopic radical nephrectomy was performed. Histopathologic diagnosis was also renal cell carcinoma. Renal cell carcinoma in patients with end-stage renal disease is fairly common and is associated with acquired cystic kidney disease. However, renal cell carcinoma associated with polycystic kidney disease is extremely rare. PMID- 17352163 TI - [Bellini duct carcinoma of the kidney: a case report]. AB - We report a case of Bellini duct carcinoma. A 65-year-old man visited our hospital because of an asymptomatic right renal mass directed by ultrasonography and computed tomography in an other hospital. His urine cytology was negative. The tumor showed a minimal enhancement in computed tomography. Under the preoperative diagnosis of an atypical right renal tumor, laparoscopic right radical nephrectomy was performed. The tumor is 50 mm in diameter and the surface was grayish-white in color. The histopathological diagnosis was low-grade Bellini duct carcinoma. Immunohistostaining revealed positive staining for UA-1 and EMA in the tumor tissue. No evidence of recurrence or metastasis was noted 36 months after surgery without any adjuvant therapy. PMID- 17352164 TI - Renal artery pseudoaneurysm after open partial nephrectomy: a case report. AB - Although intraoperative hemorrhage is a well-recognized complication of open partial nephrectomy, postoperative hemorrhage caused by a renal artery pseudoaneurysm (RAP) after open partial nephrectomy is rare. We presented a case of RAP occurring in an 84-year-old man 3 weeks after right open partial nephrectomy for renal cell carcinoma. The pseudoaneurysmal branch was successfully identified and selectively embolized using percutaneous renal arterial angiography. PMID- 17352165 TI - [Small cell carcinoma of the urinary bladder treated with neo-adjuvant cp chemotherapy (CPT-11 and CDDP): a case report]. AB - We report a cases of primary small cell carcinoma of the urinary bladder. A 68 year-old man was referred to our hospital because of asymptomatic gross hematuria. Cystoscopy showed a solid tumor on the dome of the urinary bladder. Pelvic magnetic resonance imaging (MRI) revealed a mass lesion with extravesical extention, and computed tomography(CT) scan and bone scintigraphy showed no distant metastasis. Transurethral resection of the bladder tumor (TUR-BT) was performed. Histopathological findings of the specimen showed small cell carcinoma (> pT2), with transitional cell carcinoma (TCC), grade 2-3. We performed one course of neoadjuvant CP chemotherapy using Irinotecan (CPT-11) and Cisplatin (CDDP), followed by radical cystectomy. Histopathological finding of the specimen showed no evidence of malignancy. We performed one more course of adjuvant CP chemotherapy. He has been free of disease 7 months after operation. PMID- 17352166 TI - [Giant prostate carcinoma treated effectively with endocrine therapy: case report]. AB - An 87-year-old man visited our hospital, complaining of abdominal distention and inability to urinate. Computed tomography (CT) and magnetic resonance imaging revealed a giant prostate tumor. The patient underwent percutaneous tumor biopsies. The histologic diagnosis was moderately differentiated adenocarcinoma of prostate. The clinical stage according to the TNM classification system was T4N0M0, stage IV. Combined androgen blockade therapy was performed. Four months later, CT showed that the tumor had decreased markedly in size, and the serum prostate specific antigen level was within normal range. Hormone refractory prostate cancer was not found 1 year after the start of treatment. PMID- 17352167 TI - [A case of papillary cystadenoma of the epididymis]. AB - A 74-year-old man who consulted our hospital complaining of painless left scrotal swelling. Computed tomographic demonstrated a left epididymal tumor in the hydrocele. We performed left high orchiectomy. Microscopically, several microcysts were found and tumor cells showing a papillary growth pattern were found in these microcysts. We finally diagnosed the patient as having papillary cystadenoma of the epididymis. Papillary cystadenoma of the epididymis is rare epididymal benign tumor. To our knowledge, 19 cases have been reported in Japan between 1976 and 2000. It is clinically important to determine whether or not the tumor is associated with von Hippel-Lindau disease. In our case, there was no evidence of von Hippel-Lindau disease and the patient has remained well with no complication to date. PMID- 17352168 TI - [Castleman's disease in the pelvic cavity]. AB - Although Castleman's disease may occur in any lymph node of the body, it is the most commonly found in the thoracic cavity. Castleman's disease rarely occurs in the pelvic cavity and only 18 such cases have been reported. We report a case of pelvic Castleman's disease. A 57-year-old man was referred for evaluation of a pelvic tumor. The tumor was surgically resected and the histopathological diagnosis of the resected tissue was hyaline vascular type of Castleman's disease. No evidence of disease was detected five months post-operatively. PMID- 17352169 TI - [A case of calculus in male urethral diverticulum]. AB - A 39-year-old man was admitted to our hospital because of micturition pain and swelling of the penoscrotal junction. On physical examination,a hard mass was palpated in the penoscrotal junction. Retrograde urethrography demonstrated a calculus in the diverticulum of the anterior urethra. After the suprapubic cystostomy, resection and debridment of the diverticulum were performed and the stone was removed by two-staged urethroplasty. After the operation, retrograde urethrography revealed the tissue-like urethral valve, and there was bleeding from the anastomosis of the urethra, but the patient was finally free of the disease. PMID- 17352170 TI - [Which parameters should be chosen to evaluate daily activities of the patients with chronic lung disease?]. AB - In Japan medically handicapped persons are given government support. Currently the government uses selection criteria including FEV1, PaO2, and dyspnea rating to identify level 3 handicaps, however, these criteria lack a scientific basis. The purpose of this study was to investigate the validity of the current criteria and to try to create more appropriate one. We retrospectively reviewed the clinical records of 204 cases with chronic lung disease (COPD 111, non-COPD 93). The accuracy of the current criteria was assessed by sensitivity and specificity. To find the parameters that could determine ADL, we searched for clinical parameters using simple logistic regression models, ROC curves, and cross-table analyses. To compare the accuracy of the current and newly created criteria, we assessed the sensitivity, specificity of the two criteria. Sensitivity, specificity, and overall accuracy of the current criteria were 77.6%, 74.8%, and 75.5%, respectively, however, the positive predictive value was low (46.4%). The results of the screening of the parameters showed that the following three parameters were useful discriminators of ADL: (1) supplemental oxygen use, (2) MRC scale > or =4, and (3) 6-minute walking distance <340 m. The newly created criteria using these three parameters showed better sensitivity, specificity, and overall accuracy (81.6%, 80.7%, and 80.9%, respectively) than those of the current criteria. The positive predictive value also improved. In conclusion, our results suggest that the newly created criteria that include the 6-minute walking distance are more suitable than the criteria currently used to assess the ADL of the patients with chronic respiratory disease. PMID- 17352171 TI - [Clinical study of 37 pneumonia patients in whom MRSA was identified from sputum]. AB - When we studied the clinical aspects of 37 pneumonia patients with underlying respiratory disease in whom MRSA 1 + was identified from sputum, 43.2% of these 37 pneumonia cases were diagnosed as MRSA colonization. The whole clinical course of these pneumonia patients with MRSA colonization was average 39.5 days, on the other hand, the whole clinical course of MRSA pneumonia group was 55.3 days. We should consider that MRSA must be a cause of pneumonia, in only such cases as follows; (1) patients with unstable diabetes mellitus, or with long-term administration of steroid, (2) patients with infiltrative shadows appeared not only in the lower lobe but also the upper lobe in the chest x-ray films, (3) patients with remarkable decrease of PaO2 or patients who failed to recover within one month from MRSA isolation, (4) patients with nosocomial pneumonia or patients with poor performance status or poor prognosis, (5) patients with purulent sputum containing MRSA or other bacteria such as K. pneumoniae etc and patients who failed to respond to general antibacterial agents. PMID- 17352172 TI - [Clinico-pathological prognostic factors in malignant pleural mesothelioma]. AB - The prognosis of malignant pleural mesothelioma is poor, but selected patients might benefit from multimodality treatment. To establish the means that are available to predict the variable course of the disease in malignant pleural mesothelioma patients, we retrospectively investigated the correlation of clinico pathological features of 54 patients with survival. Twenty-three patients received treatment, while 31 were referred to supportive care only. The median survival of the entire group was 8.6 months. The 1-year survival was 33.2%. Univariate analysis of subgroups showed that age over 70 years, non-epithelial histologic type, patients treated with supportive care only, and delayed diagnosis were individually associated with lower survival. The European Organization for Research and Treatment of Cancer (EORTC) score showed a significant correlation with survival (P = 0.0146). The median survival of patients with an EORTC score of over 1.27 was 3.5 months, compared to 10.5 months for patients with an EORTC score of 1.27 or less. Tumor necrosis (TN) was a poor prognostic factor on univariate analysis (P = 0.0077). Patients with TN had a median survival of 7.0 months vs 15.5 months in negative cases. On multivariate analysis, TN was determined as an independent prognostic factor (P = 0.0349). EORTC prognostic scoring systems successfully stratify survival for a general hospital population, and TN might play an important role in poor outcome in malignant pleural mesothelioma. PMID- 17352173 TI - [The methodological aspects of off-line sampling of exhaled air for nitric oxide measurement in Japanese]. AB - The measurement of exhaled nitric oxide (eNO) is a non-invasive biomarker of bronchial inflammation. Despite the usefulness of eNO measurement, NO analyzers are too expensive for widespread use by general practitioners. In comparison, the off-line (bag collection) method of eNO measurement may be more useful. In Japan, however, there have been few studies about eNO in asthmatics using the off-line method. This study shows methodological aspects of the off-line method. Briefly, with a SIEVERS bag collection kit, we recommend that the flow rate and pressure level of exhaled air should be 70 ml/sec and 10 cm H2O, respectively and that the sampled air should be measured within 12 hours. PMID- 17352174 TI - [A case of diaphragmatic paralysis caused by herpes zoster after anticancer chemotherapy]. AB - A 61-year-old woman who had been followed up after resection of lung cancer (adenosquamous cell carcinoma), was admitted to our hospital because of recurrence. She received systemic anticancer chemotherapy and the chief adverse event was leukopenia (Grade 3). Nineteen days after initiating chemotherapy, she suffered painful vesicular eruption on the right upper limb and the right upper hemithorax which was diagnosed as herpes zoster. After treatment with anti-viral drugs the vesicular eruption disappeared, but chest X-ray film revealed a right diaphragmatic relaxation. Although herpes zoster virus usually affects sensory nerves and causes painful vesicular eruption, it can also damage motor nerves. Herpes zoster virus almost affects cranial nerves, but it should be considered as the cause of diaphragmatic paralysis in this case. PMID- 17352175 TI - [Pseudotumor by asymptomatic pulmonary infarction diagnosed by video-assisted thoracic surgery]. AB - Two cases of asymptomatic pulmonary infarction were diagnosed by open lung biopsy with video-assisted thoracic surgery (VATS). Case 1: A pulmonary nodule in right S8b was pointed out in a 62-year-old man undergoing hemodialysis on chest x-ray film and CT. Case 2: A 50-year-old woman had undergone left mastectomy for mammary cancer 3 years previously and total hip replacement 1 year before. Chest X-ray film and CT revealed a pulmonary nodule in the left lower lung field and it was suspected to be metastasis of the mammary cancer. Both cases underwent open lung biopsy by VATS, and asymptomatic pulmonary infarction was revealed. When chest X-ray film shows a nodule in the lower-peripheral lung field in patients with risk factors, pulmonary infarction should be considered. PMID- 17352176 TI - [A case of primary mediastinal choriocarcinoma in which FDG-PET was performed for the evaluation of the treatment]. AB - A 61-year-old man visited another hospital with chief complaints of dry cough, appetite loss and body weight loss. On chest X ray film and CT, right supraclavicular and mediastinal lymph nodes were swollen. For further examination, he was referred to our hospital and diagnosed as primary mediastinal choriocarcinoma. We conducted surgery after four cycles of chemotherapy using cisplatin, etoposide and bleomycin. After chemotherapy, residual tumors were found on chest CT. In FDG-PET some parts of the residual tumors seen on CT showed much less uptake and the others showed similar uptake. Histologically the areas showing similar uptake contained more viable cells, and the other areas showing less uptake almost completely consisted of necrotic tissue. We believe FDG-PET can be useful to evaluate the viability of tumors after chemotherapy in extra gonadal choriocarcinoma in the mediastinum. PMID- 17352177 TI - [A case of pulmonary coccidioidomycosis]. AB - A 32-year-old Japanese woman who had been living in Arizona, United States since two years previously was admitted to our hospital because of an abnormal shadow. Her chest X-ray films revealed a small cavity in the right middle lung field which had not been identified two years ago. The chest CT showed that it was 15 mm in diameter and located in the right S6, and open lung biopsy was performed. Histological examination revealed caseous lesion of the epithelioid granulomas, that contained spherulitic forms of endospores. Fungal cultures demonstrated barrel-shaped arthroconidia. A diagnosis of pulmonary coccidioidomycosis was made. PMID- 17352178 TI - [A case of psuedocyst of the pancreas suspected to lung abscess]. AB - A 83-year-old man visited a physician because of appetite loss. The chest X-ray film showed a cavity with air-fluids sign in the left lower lung field. He was admitted to our hospital for diagnosis of the cavity lesion on a suspicion of pulmonary abscess and pulmonary tuberculosis. Amylase in fluid aspirated from the cavity was elevated to 17930 IU/l. Pseudocyst of the pancreas was diagnosed. Pseudocyst of the pancreas was considered as one of the differential diagnosis of cavities on chest X-ray film. PMID- 17352179 TI - [A case of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in a young adult successfully treated with gefitinib]. AB - The patient was a 39-year-old woman admitted with complaints of fever, clubbed fingers and arthralgia. A chest roentgenogram and chest computed tomographic scan revealed a mass in the left lower lobe. Transbronchial lung biopsy was performed, and a diagnosis of moderately differentiated adenocarcinoma was made. Physical examination confirmed finger clubbing in both hands. Bone scintigram showed marked accumulation of 99mTc-MDP in the long bones, bones of the elbows, and patellae. These findings yielded a diagnosis of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in young adult. The patient had fever and disturbance of gait of arthralgia on admission, and was treated with an oral non-steroidal anti-inflammation drug (NSAID). Advanced non small cell lung cancer (clinical stage T2 N3 M1, Stage IV) was then diagnosed. Gefitinib was administered after EGFR mutation was found in the tumor specimen. NSAID therapy alleviated the fever and arthralgia. After starting gefitinib and discontinuing the NSAID, She had kept a remission of rational symptom with cytoreductive effect. The abnormal findings of bone scintigrams subsequently disappeared and the patient's serum ICTP dropped. PMID- 17352180 TI - [Successful lobectomy in 3 lung cancer cases with severe COPD after treatment with tiotropium bromide]. AB - It is well known that lung cancer patients with severe chronic obstructive pulmonary disease (COPD) have a higher risk of postoperative complications than patients without COPD. However, the information regarding preoperative treatment to improve pulmonary function of the lung cancer patients with severe COPD is limited. Here, we report 3 lung cancer cases with severe COPD. Although all patients received medication without tiotropium bromide in combination with pulmonary rehabilitation for 1 or 2 months, their pulmonary function did not improve and the predicted postoperative FEV1/predicted FEV1 was below 40% in all cases. After the approval in Japan for use of tiotropium bromide in the treatment of COPD, all patients were treated with tiotropium bromide. The pulmonary function in all patients improved 2-4 weeks after the start of tiotropium bromide, and we performed lobectomy safely. Currently all patients maintain good pulmonary function without recurrence of lung cancer. We propose that treatment of tiotropium bromide might be one of the effective preoperative methods to improve pulmonary function of lung cancer patients with severe COPD. PMID- 17352181 TI - [A case of surgically treated primary lung cancer with myasthenia gravis]. AB - A 62-year-old woman, who had received immunosuppressive treatment for myasthenia gravis, was admitted to our hospital for the treatment of a right pulmonary tumor. In October 2003, a chest computed tomography showed a nodule-like lesion in the right lung. Two years later, the lesion was shown to have increased in size, and a right upper lobectomy was performed using video-assisted thoracic surgery. A tumor biopsy showed histological features of bronchioloalveolar carcinoma. It has been reported that malignant tumors occur more frequently in patients with myasthenia gravis with concurrent thymoma. Therefore, such patients need to be followed closely for a long period of time for any possible malignant tumor occurring in different organs. In addition, protection of the bronchial stump may be necessary to prevent a bronchial fistula, because wound healing can be delayed due to immunosuppressive treatment. PMID- 17352182 TI - [A case of pulmonary arteriovenous fistula]. AB - A 31-year-old man presenting with abrupt onset of convulsions was transported by ambulance to a nearby neurosurgery hospital. Imaging examination of the brain revealed a brain abscess in the left parietal lobe. Surgical excision of the abscess was performed. After the operation, the patient was referred to our hospital because of abnormal radio-opacities on the chest X-ray film, which were subsequently diagnosed to represent pulmonary arteriovenous fistulae in the lower lobes of both lungs. The fistulae were successfully embolized with detachable coils. Orthodeoxia (worsening of hypoxemia on assuming the upright from the supine position) was confirmed by measuring the partial pressure of oxygen in the arterial blood. We examined the shunt ratio by both the 100% O2 inhalation and 99mTc-MAA methods, and a higher ratio was obtained with the radioisotope method than with the 100% O2 inhalation method. Although it is known that the 99mTc-MAA method is more precise than the 100% O2 inhalation method, the latter is easier to perform and therefore more useful in practical clinical situations. PMID- 17352183 TI - [MicroRNA function in animal development]. PMID- 17352184 TI - [Mechanisms of molecular and neural network for thermotaxis in C. elegans]. PMID- 17352185 TI - [Potential roles of a transposon MITE in gene regulation]. PMID- 17352186 TI - [Novel RNA silencing pathway triggered by Piwi and rasiRNA]. PMID- 17352187 TI - [Mechanisms to establish left-right asymmetry in invertebrates]. PMID- 17352188 TI - [Basic principle of the segmentation clock: synchronization and robustness to noise]. PMID- 17352189 TI - [Function and structure of NAD kinase: the key enzyme for biosynthesis of NADP (H)]. PMID- 17352190 TI - [Polyamine-containing peptidoglycan and the regulation of biosynthesis of polyamines by lysine/ornithine decarboxylase in Selnomonas ruminantium]. PMID- 17352191 TI - [Current prospects for human embryonic stem cell research]. PMID- 17352192 TI - [Chariot]. PMID- 17352193 TI - [BioPORTER]. PMID- 17352194 TI - [GenomONE HVJ-E vector]. PMID- 17352195 TI - [Relationship of tumor necrosis factor alpha expression with activation of sphingomyelinase and lipid peroxidation after removal of cholestatic factor]. AB - The goal of this work was to study the expression of tumor necrosis factor alpha (TNFalpha), sphingomyelin cycle activation, and lipid peroxidation (LPO) processes after the removal of a cholestatic factor in the liver subjected to different durations of cholestasis. Restored bile flow after a 9-day hepatic cholestasis normalized sphingomyelinase (SMase) activity and levels of TNFalpha and LPO products. The removal of a cholestatic factor after a 12-day cholestasis did not normalize the studied parameters: SMase activity and the levels of TNFalpha and LPO products remained much higher compared to control. A significant positive correlation between TNFalpha expression, SMase activity, and LPO rate has been revealed. The obtained data indicate that hepatocyte apoptosis after bile outflow restoration in late cholestasis can be due to the activation of the sphingomyelin cycle, LPO, and TNFalpha expression. The synergistic interaction can sharply increase the proapoptotic capacity of each of these factors since TNFalpha activates SMase and LPO, SMase activity depends on the LPO rate, while ceramide, an SMase-produced secondary messenger of apoptosis, can induce oxidative stress. PMID- 17352196 TI - [Seasonal variation in hematological indices in bank vole (Clethrionomys glareolus) in different reproductive states]. AB - Hematological and hematopoietic indices were studied in various seasons in bank vole in different reproductive states. The seasonal variation in the indices demonstrated patterns typical of each state and reflecting the adaptive response to changed habitat conditions. PMID- 17352197 TI - [Butterflies (Lepidoptera, Diurna) in the high-mountain southeastern Russia]. AB - Groups of butterfly species established under high-mountain conditions in the southeastern Russia were described. The role of species with different distribution including arctic-alpine and alpine ones typical of these conditions in the species composition was considered. Fifteen local faunas inhabiting the areas of Buryatia, Chita, Amur, and Sakhalin Regions, and Khabarovsk and Maritime Territories were taxonomically analyzed. The common faunistic background was found in the mountains of the Mongolian-South-Siberian and East-Siberian provinces, while only some elements of the high-mountain fauna were observed at individual elevations of the South-Okhotsk province. PMID- 17352198 TI - [Significance of cardiac cannabinoid receptors in regulation of cardiac rhythm, myocardial contractility, and electrophysiologic processes in heart]. AB - Intravenous administration of cannabinoid (CB) receptor agonists (HU-210, 0.1 mg/kg; ACPA, 0.125 mg/kg; methanandamide, 2.5 mg/kg; and anandamide, 2.5 mg/kg) induced bradycardia in chloralose-anesthetized rats irrespective of the solubilization method. Methanandamide, HU-210, and ACPA had no effect on the electrophysiological activity in the heart, while anandamide increased the duration of the QRS complex. The negative chronotropic effect of HU-210 was due to CB1 receptor activation since is was not observed after CB1 receptor blockade by SR141716A (1 mg/kg intravenously) but was present after pretreatment with CB2 receptor antagonist SR144528 (1 mg/kg intravenously). CB receptor antagonists SR141716A and SR144528 had no effect on cardiac rhythm or ECG indices. Hence, in the intact heart, endogenous CB receptor agonists are not involved in the regulation of cardiac rhythm and electrophysiological processes. The chronotropic effect of CBs was independent of the autonomic nervous system because it remained significant after autonomic ganglion blockade by hexamethonium (1 mg/kg intravenously). CB receptor activation by HU-210 (0.1 and 1 microM) in vitro decreased the rate and force of isolated heart contractions, the rates of contraction and relaxation, and end diastolic pressure. The negative chronotropic effect of HU-210 was less pronounced in vitro than in vivo. The maximum inotropic effect of HU-210 was reached at the concentration of 0.1 microM. PMID- 17352199 TI - [Involvement of nitric oxide in the mechanism of adrenergic responses of systemic circulation]. AB - Increased pressor response to the infusion of alpha1-adrenoceptor agonist phenylephrine was observed in conditions of inhibited NO synthesis: the mean blood pressure increased from 33.7 to 41.1% and the total peripheral resistance increased from 6.8 to 22.0%. The effect of vasodilation induced by NO secretion in the vascular endothelium after the stimulation by alpha1-adrenoceptors on the degree of pressor changes and changes in the total peripheral resistance is proposed. PMID- 17352200 TI - [Exploratory activity of mice of different genetic strains after olfaction disruption by 3-methylindole (skatole)]. AB - The behavior of mice of two inbred strains (C57BL/6J and CBA) and their F1 hybrids was evaluated in the open field test after intraperitoneal administration of 3-methylindole (skatole) disrupting epithelium of the main olfactory system. High motor and exploratory activities and emotional sensitivity was observed in intact C57BL/6J mice compared to CBA mice and their hybrids. Anosmia induced by intraperitoneal administration of skatole changed the behavior of C57BL/6J and CBA mice. The direction of the observed changes in the orientation and exploratory behavior of anosmic animals was different. Anosmia decreased motor and exploratory activities in C57BL/6J mice and increase them in CBA mice. Intact hybrid mice demonstrated the predominance of the CBA genotype in the orientation and exploratory activity in the test used. Anosmia in hybrid animals had no significant effect on the orientation and exploratory behavior. PMID- 17352201 TI - [Quantitative patterns of development of community of Pseudomonas aeruginosa dissociants]. AB - The stationary phase of batch culture of Pseudomonas aeruginosa dissociants has been described by a variational model of consumption and growth. The generalized entropy functional was used as the objective function. The model parameters include the requirements of the dissociants for the main nutrients: carbon, nitrogen, and phosphorus. The variational model was used to calculate the limiting regions and microbial community composition during stationary growth for different initial combinations of the resources as a function of the limiting resources. A correspondence between the experimental data and model calculations has been demonstrated. A possibility to control the community structure is discussed. PMID- 17352202 TI - [Feeding and growth of Japanese scallop inhabiting different bottom sediment types]. AB - Two parts of the population of Japanese scallop Mizuhopecten yessoensis inhabiting sites with different bottom sediments in an open part of Peter the Great Bay of the Sea of Japan were compared. The scallops grew slower on muddy site compared to sandy site despite better food availability at muddy site. The food sources were determined using fatty acids as biomarkers. Analysis of the fatty acid composition of the scallops has identified diatom plankton, flagellates, and invertebrate larvae as the main scallop food sources. Benthic bacteria insignificantly contributed to the scallop diet. The food composition slightly varied in scallops on different sediment types. Most likely, low oxygen content in water, high resuspension of fine sediment particles rich in dead organic matter, and high content of contaminants accumulated in muddy sediments are the main factors of decelerated growth of scallops on muddy sites. PMID- 17352203 TI - [Heat resistance of the skeletal muscle in western palearctic green frogs (Rana esculenta complex)]. AB - Heat resistance of the gastrocnemius muscle was studied in five species of the Rana esculenta complex. It was similar in R. bedriagae, R. lessonae, and in the European form of R. ridibunda; while North African R. saharica demonstrated a lower heat resistance. No heterosis was expressed in R. esculenta, a clonal hybrid of R. lessonae and R. ridibunda, for the heat resistance of the muscle. Moreover, this species demonstrated low heat resistance at the highest test temperatures (42 degrees C). Comparison of diploid and triploid R. esculenta syntopically occurring in the same water bodies demonstrated no heat resistances between them, thus, suggesting that polyploidy has no effect on this parameter at least in this case. PMID- 17352204 TI - [Transformation of Fe, Mn, Co, and Ni compounds in humic podzols at different moisture]. AB - Incubation of humic podzol at soil moisture of 60 and 100% field capacity (FC) and after addition of peat and glucose increased the content of nickel and cobalt compounds in the water-soluble, exchangeable, organic matter-bound, and amorphous iron-bound fractions. At the same time, the content of elements bound to crystallized iron compounds decreased twofold and fourfold at 60 and 100% FC, respectively. The content of cobalt and nickel decreased in the residual fraction by 25 and 50%, respectively. The transformation of cobalt and nickel in soil is closely related to the transformation of iron and manganese compounds as well as to redox processes. The lowest pH and redox potential (RP) as well as the highest increase in the mobility of the elements was observed after soil incubation with glucose at 100% FC. PMID- 17352205 TI - [A model study of pesticide biodegradation in soil]. AB - This study addresses the efficiency of microbial preparations to degrade pesticide residues in soil. A method to degrade pesticides DNOC and pendimethalin using Pseudomonas and Arthrobacter bacteria with a fertilizer is described. PMID- 17352206 TI - [Effect of red light on activity of cAMP phosphodiesterases in photoperiodically different cereals and vernalized winter wheat]. AB - Red light illumination of seedlings of photoperiodically different cereals had a different effect on the activity of multiple cyclic adenosine monophosphate phosphodiesterases. The response of all phosphodiesterase forms was reversed in fully vernalized winter wheat Triticum aestivum L. PMID- 17352207 TI - [Microflora patterns in oil-contaminated soils]. AB - The method of glass slides was modified to study the dynamics of microbial cenoses in oil-contaminated soils. The resulting microflora patterns can be clearly distinguished between soil types and oil quality and utilization. PMID- 17352208 TI - [Biogeoenergetic description of soils in natural landscapes of Georgia]. AB - Energy consumed for soil formation and efficiency of solar energy utilization have been comparatively evaluated for various soil types in natural landscapes of Georgia. Soil formation proved to consume 16-87% of energy of the radiation balance at the surface, while cyclic biological processes consumed 0.162-1.344 kcal/(cm2 year). PMID- 17352209 TI - Establishment of human cancer cell clones with different characteristics: a model for screening chemopreventive agents. AB - BACKGROUND: The present study was undertaken in order to establish phenotypically different cell clones from 10 parental lines of human breast (MCF-7 and T-47D), prostate (PC-3 and DU145), lung (A549 and A427), colon (HCT-116 and HT-29) and bladder (TCCSUP and T24) cancer cells. MATERIALS AND METHODS: Sublines were established from each of the parental lines by the limiting dilution method. The derived clones were characterized in terms of plating efficiency, cell proliferation rate, saturation density and colony formation efficiency in soft agar. RESULTS: Phenotypically different cell clones were derived from each parental human cancer cell line, with many clones having more 'normal' characteristics than the parental line from which they were derived. CONCLUSION: Phenotypically normal clones obtained through clonal selection from human cancer cell populations are expected to be a useful tool for the screening of cancer chemopreventive agents and the study of tumor progression. PMID- 17352210 TI - Polymorphonuclear leukocytes increase the adhesion of circulating tumor cells to microvascular endothelium. AB - BACKGROUND: Reactive oxygen species (ROS) released from activated polymorphonuclear leukocytes (PMN) during surgery may play a crucial role in the enhanced distant tumor recurrence after surgical trauma. MATERIALS AND METHODS: The effect of PMN on the adhesion of the human colon carcinoma cells HT29, Caco2 and the pancreatic carcinoma cells PanC1 and BxPC3 to microvascular endothelium (MEC) was studied in a reproducible human in vitro model. RESULTS: Pre-incubation of MEC with tissue plasminogen activator (TPA)-activated PMN resulted in more than 200% increase of tumor cell adhesion to MEC compared to control (p < 0.01). Exposure of MEC to TPA or non-activated PMN did not significantly affect adhesion. Addition of the antioxidant enzymes superoxide dismutase or catalase significantly decreased tumor cell adhesion to MEC exposed to PMN. CONCLUSION: These results demonstrate that activated PMN promote tumor cell adhesion to the microvascular wall by production of ROS. This indicates that in tackling the ROS production, preventing tumor recurrence at distant sites, might be feasible. PMID- 17352211 TI - Tumour suppressor protein (p53), apoptosis inhibiting protein (Bcl-2) and proliferating cell nuclear antigen (PCNA) expressions in a rat pancreatic tumour model. AB - BACKGROUND: Previous studies have shown that, cultured rat pancreatic carcinoma cells, derived from azaserine-induced acinar tumours, yield tumours with a ductal phenotype. MATERIALS AND METHODS: In order to find out the molecular characteristics of this tumour model, tumour suppressor protein (p53), apoptosis inhibiting protein (Bcl-2) and proliferating cell nuclear antigen (PCNA) expressions were analysed in rat pancreatic and subcutaneous tumours, as well as in normal rat pancreas. RESULTS: Immunoreactivity for p53 protein was found in 86% of intrapancreatic tumours and in 100% of subcutaneous tumours. The average fraction of positive carcinoma cells was over 50%. Normal rat pancreas showed only slight positive or negative staining for p53. Bcl-2 did not show positive immunoreactivity in rat tumour samples. For PCNA all tumour samples showed positive staining. Also normal pancreas of 6-week-old animals were clearly positive, whereas the samples of the older animals were only slightly positive. CONCLUSION: Possible mutations in the p53 tumour suppressor gene and a strong expression of PCNA were shown in carcinoma cell line-induced rat pancreatic tumours. These features of the rat pancreatic tumour model resemble human pancreatic carcinoma and may favour the use of this model in pancreatic cancer studies. PMID- 17352212 TI - MRNA stability and overexpression of fatty acid synthase in human breast cancer cell lines. AB - BACKGROUND: Elevation of fatty acid synthase (FAS) in human cancers is often associated with increased tumor aggression. The basic genetic mechanisms leading to increased enzyme content in cancer cells were investigated using cell lines derived from human metastatic breast carcinomas (T47D, Zr75 and SKBr3) and normal human breast epithelium (184A1). MATERIALS AND METHODS: Western analysis, Northern blotting, [2-(14)C]malonyl-CoA incorporation assays, nuclear run-off transcription assays, mRNA decay assays, and poly(A) tail assays were used to measure and compare transcription rates of the FAS gene among the four cell lines. RESULTS: By Western analysis, FAS levels in T47D were 2.6 times lower than ZR75 and SKBr3, but 6.7 times greater than non-neoplastic 184A1 cells. FAS mRNA levels and specific activity correlated with protein content. In contrast, relative rates of FAS gene transcription were significantly higher in non neoplastic 184A1 cells than T47D, ZR75 and SKBr3. Stability of message was investigated to explain this discrepancy. The half-life of FAS mRNA in 184A1 cells was 5.6 h, or 4-5-fold less than ZR75 and SKBr3. Poly(A) tail assays showed that FAS mRNA species from 184A1 cells tended to be longer than those of breast cancer cell lines (500-1500 nt versus 500-800 nt, respectively). CONCLUSION: Breast cancer cell lines contained significantly more FAS enzyme, message and activity than non-neoplastic 184A1 cells. Yet, 184A1 cells exhibited higher rates PMID- 17352213 TI - Measuring cytotoxicity: a new perspective on LC50. AB - BACKGROUND: Cytotoxicity in cell culture is typically expressed as LC50 the concentration of a given agent which is lethal to 50% of the cells. This number is dependent on the incubation time with the agent. Previously, a two-term exponential model has been proposed to describe cell growth after a cytotoxic event: y(t) = k, * exp(-d(1)*t) + k2 * exp(d(2)*t). A dose-response relationship was observed between the parameter k2 in this formula and the concentration of the cytotoxic agent etoposide, in high-grade glioma cells was independent of incubation time. MATERIALS AND METHODS: In order to test if the model can be applied more generally, DAOY medulloblastoma cells treated with MS275, a histone deacetylase inhibitor, were used. RESULTS: The observed data fit the model well. CONCLUSION: The concentration at which k2 is reduced by 50% is called KC50. It provides a far better description of the cytotoxicity of an agent in a specific cell line than the traditional LC50. PMID- 17352214 TI - Stathmin is overexpressed in malignant mesothelioma. AB - BACKGROUND: Malignant pleural mesothelioma is a highly aggressive cancer, with low overall survival. The pathogenesis of mesothelioma is poorly understood. The aim of this study was to identify potential genes overexpressed in mesothelioma. MATERIALS AND METHODS: A cDNA microarray was used to identify potential genes that are activated in mesothelioma cell lines. Overexpression of stathmin, a cytosolic protein that regulates microtubule dynamics, was found. RT-PCR, Western blot, and immunohistochemistry were used to confirm overexpression in both cell lines and tumor samples. RESULTS: Using RT-PCR and Western blot, stathmin overexpression was confirmed in seven mesothelioma cell lines. Increased stathmin protein expression was also found in seven out of eight mesothelioma tumor samples. Finally, stathmin expression in a mesothelioma tumor was confirmed by immunohistochemistry. CONCLUSION: For the first time, stathmin was shown to be overexpressed in malignant mesothelioma. The overexpression of stathmin in mesothelioma may offer a potential therapeutic target and further studies are warranted. PMID- 17352215 TI - Three-dimensional cellular spheroid formation provides human prostate tumor cells with tissue-like features. AB - BACKGROUND: Alterations in the cellular biological responses were examined in a series of LNCaP human prostate tumor cells growing under different conditions. MATERIALS AND METHODS: LNCaP cells were grown in two-dimensional monolayer cultures, three-dimensional spheroids, or as solid tumors in immune-deprived mice. RESULTS: As compared with the growth in the monolayers, cell growth in the spheroids was reduced, while VEGF production was increased. Immunohistochemical analysis of the spheroids revealed that cells showing Ki-67 up-regulation were localized in the peripheral layer, and that the central core was necrotic. The gene expression profile in the solid tumor tissue was obviously different from that in the monolayers; however, it was similar to that in the spheroids. The prostate-specific antigen levels in the culture supernatants of spheroids increased with time and decreased with anticancer agent treatment. CONCLUSION: Spheroid formation from human prostate tumor cells exhibits tissue-like features. PMID- 17352216 TI - The biological relevance of FHL2 in tumour cells and its role as a putative cancer target. AB - The LIM-only protein FHL2 (four-and-a-half LIM-domain protein 2) belongs to the FHL protein family of transcriptional cofactors present in various cell lines. FHL2 interacts with a variety of transcription factors known to be involved in tumour development. Furthermore, FHL2 expression is often deregulated in cancer including overexpression and down-regulation in various types of tumours. The function of FHL2 in cancer is particularly intriguing, since it may act as an oncoprotein or as a tumour suppressor in a tissue-dependent fashion. This dual nature of FHL2 is also reflected by the finding that it can function as repressor or activator of transcriptional activity depending on the cell-type. The ability of FHL2 to exert functional diversity lies within its structural composition as a LIM-only protein. LIM-domains are enzymatically inactive protein-to-protein interaction domains, which determine the function of LIM-only proteins as adaptor molecules or scaffolding proteins. By selectively using different LIM-domains for protein-to-protein interactions, FHL2 is capable to interact with a broad spectrum of functionally unrelated proteins, thereby triggering different signalling pathways. In this review, the current knowledge of FHL2 expression in different cancers was summarized and the interaction of FHL2 with transcription factors and other proteins involved in cancer development was examined. Since transcription factors control all fundamental developmental and homeostatic processes, transcriptional cofactors like FHL2 are likely to contribute to human carcinogenesis and are of clinical importance in various forms of cancer. PMID- 17352217 TI - Correlation of DNA mismatch repair protein hMSH2 immunohistochemistry with p53 and apoptosis in cervical carcinoma. AB - BACKGROUND: Mutations in genes of the DNA mismatch repair system (MMR) are linked to hereditary non-polyposis colorectal cancer and also play a role in sporadic cancer. Besides its repair function, the MMR is the linkage of DNA mismatch recognition to the cell cycle control. MATERIALS AND METHODS: The correlation between the immunoreactivity of the MMR protein hMSH2 and p53, apoptosis, clinical prognosis factors and the survival rate in 102 samples of cervical carcinoma was determined. RESULTS: hMSH2 immunoreactivity was correlated with p53 and weakly correlated with apoptosis. hMSH2 immunoreactivity could not be correlated to any tumour markers, while apoptosis correlated significantly with T stage, FIGO classification and the relative risk of death from cervical cancer. CONCLUSION: In cervical cancer, the processes of DNA mismatch repair, cell cycle control and apoptosis seemingly act in concert. Decreased expression of the hMSH2 mismatch repair protein might lead to a failure in the induction of apoptosis. PMID- 17352218 TI - Short tandem repeat polymorphisms of exon 4 in Kazal-type gene ECRG2 in pancreatic carcinoma and chronic pancreatitis. AB - BACKGROUND: Short tandem repeat (STR) polymorphisms in exon 4 of the Kazal-type esophageal cancer related gene (ECRG2) have been reported to be associated with esophageal carcinoma. Kazal-type genes are associated with cancer and pancreatic disease. The aim of the present study was to examine whether ECRG2 STR polymorphisms are associated with pancreatic carcinoma and chronic pancreatitis. MATERIALS AND METHODS: A total of 209 surgically treated patients were analyzed, 92 with pancreatic adenocarcinoma and 117 with chronic pancreatitis. We retrospectively analyzed genomic DNA from peripheral blood leukocytes for STR TCA3/TCA3, TCA3/TCA4 and TCA4/TCA4 in the noncoding region of exon 4 of ECRG2. Associations between STRs and survival of cancer patients were investigated using log-rank test. RESULTS: ECRG2 STR of highest incidence was TCA3/TCA3 [47 (51%) in pancreatic carcinoma; 59 (50%) in pancreatitis patients], followed by the TCA3/TCA4 [37 (40%); 54 (46%)] and TCA4/TCA4 [8 (9%); 4 (4%)] genotypes. No correlation in frequency of STRs comparing chronic pancreatitis and pancreatic cancer was determined using the Chi-squared test (p = 0.23). STR polymorphisms were not significantly associated with reduced tumor-specific or overall survival (p > 0.05; log-rank test). CONCLUSION: The data show that ECRG2 STR polymorphism TCA3/TCA3 in exon 4 is the most prevalent polymorphism found in pancreatic adenocarcinoma and chronic pancreatitis detected in peripheral blood. None of the polymorphisms was associated with poor clinical outcome in pancreatic cancer patients. PMID- 17352219 TI - FTY720 induced Bcl-associated and Fas-independent apoptosis in human renal cancer cells in vitro and significantly reduced in vivo tumor growth in mouse xenograft. AB - BACKGROUND: A unique immunosuppressant, FTY720, selectively induces apoptosis in activated lymphocytes, but not in other hematopoietic cells. The potential that this unique mechanism could provide anticancer potential by inducing apoptosis in the human renal cancer cell line, ACHN, which is resistant to cisplatin, and its molecular pathway was investigated. MATERIALS AND METHODS: The difference in drug susceptibility to FTY720 between cancer cells and non-cancer cells was examined by MTT assay and flow cytometry. Apoptosis assay, including TUNEL staining, electron microscopy and DNA electrophoresis, was performed and the molecular pathway of FTY720 was evaluated by real time RT-PCR and Western blot. The in vivo effect of FTY720 was evaluated using a murine zenograft model. RESULTS: The susceptibility to FTY720 was significantly higher in ACHN cancer cells than in normal renal tubular cells (HK-2) at a concentration of less than 30 microM, while the susceptibility to cisplatin was even higher in HK-2 than in ACHN. Cancer cells treated with FTY720 showed findings typical of apoptosis with highly condensed nuclear chromatin and fragmented nuclei. The molecular analysis revealed that FTY720-induced apoptosis was mediated by a Fas-independent, Bcl associated signal transduction pathway, and that inhibition of extracellular signal-regulated kinase (ERK) activity was involved in its underlying mechanism of action. FTY720 treatment significantly prevented in vivo tumor growth without any severe adverse reactions, while cisplatin treatment did not inhibit tumor growth despite exhibiting severe side-effects. CONCLUSION: FTY720 may be a promising candidate for a new anticancer therapy of renal cancer. PMID- 17352220 TI - Transcriptional regulatory regions of the survivin gene activate an exogenous suicide gene in human tumors and enhance the sensitivity to a prodrug. AB - Selective expression of a therapeutic gene in tumors contributes to the efficacy and the safety of cancer therapy. Regulatory regions of genes that are preferentially expressed in tumors have been examined. The regions of the survivin gene exhibited the greatest activity in human hepatocellular carcinoma cells. Deletion of the survivin regulatory region from the 5'-side demonstrated that the 0.5 kb and the 1.4 kb fragments possessed a strong promoter activity with relative tumor specificity. Human tumors transfected with the herpes simplex virus-thymidine kinase gene, that was powered by the survivin region, became susceptible to a prodrug, ganciclovir. Although survivin gene expression was up regulated in the G2/M-phase of the cell cycle, taxol or vincristine treatment, which induce cell cycle arrest at the M-phase, did not enhance the transcriptional activity of the survivin promoter. These data collectively suggest that the survivin regulatory region induces the expression of an exogenous gene in tumors, but the transcriptional activity is not directly linked with M-phase induction. PMID- 17352221 TI - Significance of matrix metalloproteinase-7 [correction of matrix metalloproteinase-2], -11 and tissue inhibitor of metalloproteinase-1 expression in normal, hyperplastic and neoplastic endometrium. AB - BACKGROUND: Matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) are key factors in the degradation of extracellular matrix and basement membranes. This study aimed to examine the expressions of MMP 7 and -11 and TIMP-1 in normal, hyperplastic and neoplastic endometrium and their correlation to clinicopathologic factors. PATIENTS AND METHODS: Tissue samples of 40 normal endometria, 20 endometrial hyperplasias and 120 endometrial endometrioid adenocarcinomas were used for the study. Immunohistochemical staining for MMP-7 and -11 and TIMP-1 protein was performed on formalin-fixed and paraffin-embedded tissue samples. These expressions were represented as incidence of expression. RESULTS: MMP-7 was highly expressed in the glands of the basal and functional layers during the proliferative and menstrual phases. MMP-11 expression in the gland of the basal layer and the stroma of the functional layer fluctuated during the menstrual cycle. TIMP-1 was highly expressed in the late secretory and menstrual phases. MMP-7 was expressed at significantly higher levels in endometrial hyperplasia than normal endometrium, whereas MMP-11 was expressed at lower levels. In endometrial adenocarcinoma, MMP-7, MMP-11 and TIMP 1 were expressed at the same levels as in hyperplasia. MMP-7 expression in endometrial carcinoma was correlated with myometrial invasion and estrogen receptor expression. The expression of MMP-7 in the adjacent stroma was associated with a poor prognosis. CONCLUSION: MMP-7, MMP-11 and TIMP-1 expression may be regulated by the menstrual cycle, and related to the degradation and remodeling of the normal endometrium. MMP-7 expression might be a prognostic factor in endometrial carcinoma. PMID- 17352222 TI - Modulation of multidrug resistance gene expression in human breast cancer cells by (-)-gossypol-enriched cottonseed oil. AB - BACKGROUND: Multidrug resistance (MDR) is a major impediment to successful cancer chemotherapy. P-glycoprotein (P-gp), the product of the multidrug resistance 1 (MDR1) gene, acts as an efflux pump and prevents sufficient intracellular accumulation of several anticancer agents, thus, playing a major role in MDR. Tamoxifen (Tam), ICI 182 780 (ICI) and Adriamycin (Adr) alone or with (-) gossypol-enriched cottonseed oil [(-)-GPCSO] possible effects on cell growth inhibition and regulation of MDR1, mRNA and P-gp expression were examined in both an MDR human breast cancer cell line, MCF-7/Adr cells, and primary cultured human breast cancer epithelial cells (PCHBCEC). MATERIALS AND METHODS: Cells were treated with 0.05% of (-)-GPCSO either in the absence or presence of either 0.1 microM Tam, ICI or Adr for 24 h. RESULTS: Using the non-radioactive cell proliferation MTS assay, none of these chemotherapeutic agents alone inhibited MCF-7/Adr cell and PCHBCEC proliferation; meanwhile, the combination of 0.1 microM Tam, ICI or Adr with 0.05% (-)-GPCSO significantly reduced MCF-7/Adr cell growth by approximately 34%, 32% and 23%, respectively, of that of the vehicle treated cells. For PCHBCEC, the combination of 0.05% (-)-GPCSO with 0.1 microM of Tam, ICI and Adr reduced cell growth to about 94%, 90%, and 71% respectively, of the vehicle treated PCHBCEC. Furthermore, (-)-GPCSO inhibited MDR1/P-gp expression in both MCF- 7/Adr and PCHBCEC in a dose-dependent manner. Our results provide insight into the MDR-reversing potential of (-)-GPCSO in human breast cancer cells resistant to current chemotherapeutic agents. PMID- 17352223 TI - ROS mediates baicalin-induced apoptosis in human promyelocytic leukemia HL-60 cells through the expression of the Gadd153 and mitochondrial-dependent pathway. AB - BACKGROUND: Chemotherapy agents, particularly those that can induce apoptosis, are the major intervening strategy in the treatment of leukemia. In this study, we investigated the effects of baicalin (a compound obtained from Scutellaria baicalensis Georgi and S. rivularis Benth Labiateae) on the viability, induction of apoptosis and associated mechanism in human leukemia HL-60 cells. MATERIALS AND METHODS: The cell viability and apoptosis was examined by flow cytometric analysis. The results showed that baicalin induced cytotoxicity in a dose- and time-dependent manner through the activation of caspase-3, as shown by treatment of HL-60 cells with an inhibitor of caspase-3 (z-VAD-fmk). Baicalin increased the levels of ROS, Ca2+ and decreased mitochondrial membrane potential in HL-60 cells. Western blot demonstrated that baicalin promoted the levels of Gadd153, Bax, cytochrome c and caspase-3 and -12, but decreased the levels of Grp78 and Bcl-2 in HL-60 cells. CONCLUSION: Baicalin was found to induce apoptosis in HL-60 cells through multiple pathways. PMID- 17352224 TI - Overexpression of human X-box binding protein 1 (XBP-1) in colorectal adenomas and adenocarcinomas. AB - BACKGROUND: Human X-box binding protein 1 (XBP-1) is a transcription factor essential for hepatocyte growth, as well as for plasma cell differentiation. Recently, overexpression of XBP-1 has been reported in breast cancer including non-invasive carcinomas, and was suggested to play an important role in breast carcinogenesis. To investigate the involvement of XBP-1 in colorectal tumorigenecity, the expression of XBP-1 was examined in four colon cancer cell lines, six colorectal polyps and five colorectal carcinomas. MATERIALS AND METHODS: The study population consisted of eleven patients who had undergone resection for colorectal cancer or adenoma from 2000 to 2002. Four colon cancer cell lines, DLD1, SW480, HCT15 and WiDr, were also analyzed for expression of XBP 1. Reverse transcription-polymerase chain reaction was performed using eleven primary colon tumors. XBP-1 expression was then investigated using an immunohistochemical method for archived paraffin-embedded sections. RESULTS: The XBP-1 gene was overexpressed in four cases out of five primary colorectal carcinomas and in four cases out of six colorectal adenomas. Also all four cancer cell lines expressed XBP-1 mRNA. Immunohistochemical staining demonstrated that XBP-1 protein was strongly stained in the cytoplasms of cancer cells, whereas it was unreactive in the normal colon epithelial cells and stromal cells. CONCLUSION: These data indicate that increased expression of XBP-1 gene may play some role in human colon carcinogenesis through impairment of cell differentiation regulation. PMID- 17352225 TI - Tumor-specificity and type of cell death induced by trihaloacetylazulenes in human tumor cell lines. AB - Twenty trihaloacetylazulene derivatives with one atom of fluorine, chlorine, bromine or iodine was investigated for their tumor-specific cytotoxicity and apoptosis-inducing activity against three human normal cells (gingival fibroblast, HGF; pulp cell, HPC; periodontal ligament fibroblast, HPLF) and four human tumor cell lines (squamous cell carcinoma, HSC-2, HSC-3, HSC-4; promyelocytic leukemia, HL-60). There was no apparent difference in the cytotoxic activity between 2-methoxyazulenes [1a-1e, 2a-2e] and 2-ethoxyazulenes [3a-3e, 4a 4e]. Trichloroacetylazulenes [2a-2e, 4a-4e] generally showed higher cytotoxicity and tumor-specificity (expressed as a TS value) as compared with the corresponding trifluoroacetylazulenes [1a-1e, 3a-3e]. Substitution of chloride [1c, 2c, 3c. 4c], bromide [1d, 2d, 3d, 4d] or iodine [1e, 2e, 3e, 4e] at the C-3 position further enhanced cytotoxic activity against four tumor cell lines, especially HL-60 cells. Among twenty trihaloacetylazulene derivatives, two compounds [2d] and [4c] showed the highest tumor specificity (TS = > 3.5 and > 2.5, respectively). Compounds [2d] and [4c] induced apoptotic cell death characterized by caspase-3, -8 and -9 activation and internucleosomal DNA fragmentation in HL-60 cells. On the other hand, compounds [2d] and [4c] induced autophagic cell death characterized by lower activation of caspases, lack of DNA fragmentation, vacuolization and autophagosome formation detected by acridine orange and LC3-GFP fluorescence, without the decline of the intracellular concentration of three major polyamines in HSC-4 cells. The cytotoxic activity of [4c], but not [2d], was slightly reduced by 3-methyladenine, an inhibitor of autophagy. These results suggest the diversity of cell death type induced in human tumor cell lines by trihaloacetylazulene derivatives. PMID- 17352226 TI - Up-regulation of matrix metalloproteinase family gene involvement in ursolic acid induced human lung non-small carcinoma cell apoptosis. AB - Ursolic acid is a triterpenoid reported to inhibit the invasion of cancer cells. In this study, there was a significant increase in the gene expression of matrix metalloproteinase (MMP)-1, -2 -3, -9 and -10 in H460 cells after treatment with 10 microM ursolic acid for 24 h. Under these experimental conditions, it was found that ursolic acid induced H460 cell apoptosis. These results indicated that matrix metalloproteinase family members are involved not only in invasion, but also in apoptosis of cancer cells. It has been suggested that ursolic acid acts via a glucocorticoid receptor in the regulation of MMP. Our study also demonstrated that the localization of glucocorticoid receptor in the cytosol might be an important factor of MMP up-regulation during ursolic acid-induced H460 cell apoptosis. Ursolic acid induced a typical apoptosis on H460 cells, which was characterized by the activation of caspase-3, nuclear morphological changes and DNA fragmentation. PMID- 17352227 TI - Comparative biology of human and canine osteosarcoma. AB - Dogs with osteosarcoma provide an important model for the same disease in humans. In this report, the comparative nature of human and canine osteosarcoma including incidence and risk factors, clinical presentation and diagnosis, genetic abnormalities, biologic behaviour and prognostic factors, as well as treatment options are reviewed. PMID- 17352228 TI - Renal cell carcinoma-induced immunosuppression: an immunophenotypic study of lymphocyte subpopulations and circulating dendritic cells. AB - BACKGROUND: Renal cell carcinoma (RCC)-induced immune dysfunction in patients at first diagnosis was investigated. PATIENTS AND METHODS: The main circulating lymphocyte subsets, the total number of circulating and intratumor dendritic cells and the titers of circulating VEGF were quantified in 47 RCC patients, using flow cytometric, immunohistochemical and ELISA assays. RESULTS: Despite a significant activation of CD3/HLA-DR+ lymphocytes and of the CD56+ NK subset, RCC patients presented a marked immunosuppression of CD4/CD45RA naive T-cells, CD4/CD45RO memory T-cells, CD16+ NK-cells, and total circulating dendritic cells, as well as a significant increase of lymphocytes co-expressing the CD4 and CD8 antigens. Finally, CD16+/CD56+ NK and DCs were poorly represented in tumor specimens. CONCLUSION: The complex immunological dysfunctions demonstrated involve different levels of immunocompetence and indicate a pattern of major disturbance of the immune system. PMID- 17352229 TI - Association between duodenal contents reflux and squamous cell carcinoma- establishment of an esophageal cancer cell line derived from the metastatic tumor in a rat reflux model. AB - Squamous cell carcinoma (SCC) of the human esophagus has a multifactorial etiology involving several environmental and/or genetic factors. Recently, gastroesophageal reflux has been implicated as a causative factor in upper aerodigestive tract carcinogenesis. The development of esophageal squamous cell carcinoma (ESCC) in a duodenal contents reflux model without any known carcinogen present has been reported previously. In this study, the duodenal contents reflux model without gastrectomy was used. At 60 weeks post-operatively, all surviving animals had malignant lesions as follows: ESCC (40%), esophageal adenocarcinoma (EAC) (20%) and adenosquamous carcinoma (40%). In one subject, a well differentiated ESCC was detected with thoracic dissemination and metastases in lymph nodes. A novel cell line, designated ESCC-DR, was established from the thoracic metastatic tumor at the 60th post-operative week. These cells were transplanted into nude mice, and the developed nodules represented a well differentiated ESCC, resembling that of the parent site. Duodenal contents reflux has a great potential for malignant initiation and plays a role in developing not only EAC but also ESCC. PMID- 17352230 TI - Evaluation of insulin-like growth factor-1 in a mouse model of long-term abdominal radiation toxicity. AB - The purpose of these experiments was to test whether a brief course of insulin like growth factor-1 (IGF-1) injection (escalating doses) concomitant to irradiation ameliorates radiation-induced kidney dysfunction and lethal bowel toxicity in a mouse model of unilateral high-dose irradiation of the kidney and adjacent bowel. The kidney function was assessed by means of repeated 99mTc dimercaptosuccinate scans (every six weeks) during a maximum follow-up of 49 weeks. The experiments with single fractions of 12 Gy and 15 Gy revealed only minor differences in the severity of kidney dysfunction and no reduction in lethal bowel toxicity from IGF-1 treatment In the absence of any significant radioprotective effect, other strategies of response modification need to be developed. PMID- 17352231 TI - Potent cytotoxic activity of Saururus cernuus extract on human colon and breast carcinoma cultures under normoxic conditions. AB - BACKGROUND: Saururus cernuus (Sc) is a small plant, used for the treatment of various human inflammations. The present study aimed at investigating the cytotoxic potential of the methanolic extract of this plant against brine shrimp larvae and human carcinoma cells at normoxic conditions. MATERIALS AND METHODS: The in vivo lethality test was evaluated at various doses against brine shrimp larvae at different time periods. Similarly, the extract was tested for 48 h at various concentrations against human CL-18 and MDA-MB-231 carcinoma cell lines and the toxicity was evaluated using the dye binding crystal-violet assay method. RESULTS: In the shrimp assay, the extract was very active, with ED50 values ranging from 1.83 +/- 0.2 to 2.79 +/- 0.2 microg/ml at various incubation periods. The extract was also very potent in human CL-18 and MDA-MB-231 cultures with LD50 values of 1.9 +/- 0.17 and 0.26 +/- 0.03 microg/ml, respectively. CONCLUSION: The results of this study indicate that Sc extract contains very stable, potent anticancer compounds, which gain access into the cells quickly and kill carcinoma cells and shrimp larvae at normoxic conditions. PMID- 17352232 TI - Antitumor activity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs. AB - BACKGROUND: Gemcitabine is a deoxycytidine analogue that exhibits antitumoral activity against adenocarcinomas of the colon, lung and pancreas. After intravenous injection, gemcitabine is rapidly converted to the inactive metabolite 2'-deoxy-2',2'-difluorouridine by cytidine deaminase. MATERIALS AND METHODS: To improve the pharmacokinetic behavior and the antitumor activity of the drug, the gemcitabine prodrug, 4-(N)-stearoylgemcitabine (C18gem) was incorporated in liposomes and both the pharmacokinetic and the in vivo activity of this formulation intravenously or peritumorally administered in nude female CR1:Nu/Nu(CD-1)BR mice grafted with HT-29 and KB 396p cells were studied. RESULTS: The C18gem-liposomes showed both higher plasma half life and tumor regression than control and gemcitabine. CONCLUSION: The incorporation of C18gem prodrug in liposomes increased the plasma half life of the drug resulting in increased accumulation in the tumor cells and a higher level of antitumoral efficacy. The results obtained with different tumors sensitive to gemcitabine support the efficacy of this proposed drug delivery system. PMID- 17352233 TI - Macrocyclic lathyrane diterpenes as antitumor promoters. AB - Human cytomegalovirus (CMV) preferentially infects tumor tissues and the accumulated CMV immediate-early (IE) antigen may lead to tumor promotion and progression. The development of strategies to inhibit human CMV IE antigen expression and/or function is an important goal to prevent and treat certain forms of cancers associated with human CMV. The aim of this study was to search for antitumor promoters from plant sources. The effect of six macrocyclic lathyrane-type diterpenoids, latilagascenes A-E (1-5) and jolkinol B (6), isolated from the methanol extract of Euphorbia lagascae, on the expression of IE antigen in lung cancer cells (A549) infected by CMV was studied. All the compounds, except latilagascene D (4), decreased IE antigen expression of CMV. PMID- 17352234 TI - The proteasome inhibitor bortezomib augments anti-proliferative effects of mistletoe lectin-I and the PPAR-gamma agonist rosiglitazone in human melanoma cells. AB - BACKGROUND: The NFkappaB signalling pathway plays an important role in chemoresistance and decreased apoptosis. One indirect way to inhibit the NFkappaB pathway is to slow down the proteasomal degradation of its inhibitor IkappaB, thus preventing NFkappaB from translocation into the nucleus. Hence, the effect of the proteasome inhibitor bortezomib (Velcade) on the cell proliferation of the MV3, FemX-1 and G361 human melanoma cell lines and its action in combination with the PPAR-gamma agonist rosiglitazone or the mistletoe lectin ML-I, both having anti-proliferative effects on melanoma cells in single agent use, was investigated. MATERIALS AND METHODS: Proliferation of melanoma cells under the different treatment regimes over a broad concentration range (0.0001-100 microg/ml) was assessed by means of the XTT cell proliferation assay. RESULTS: At a concentration of 0.1 microg/ml bortezomib significantly reduced the proliferation rate of all melanoma cells to 1-13% of the control, which was mediated through increased apoptosis and inhibition of NFkappaB expression. Furthermore, the combination of bortezomib and rosiglitazone was the most potent and increased the effectiveness against melanoma cell growth by 63-71% (compared to single use of rosiglitazone) and by 27-39% (compared to single use of bortezomib), respectively. CONCLUSION: This combination strategy might be a promising approach for future melanoma therapy. PMID- 17352235 TI - Fas/Fas-ligand expressions in primary breast cancer are significant predictors of its skeletal spread. AB - BACKGROUND: Bones belong to the most frequent localizations of breast cancer metastases. Several studies on female breast malignancies have indicated that Fas/Fas-ligand status may have a significant impact on survival. Hence, the aim of our study was to determine if these molecules might serve as the predictors of skeletal dissemination in radically-treated breast cancer patients. PATIENTS AND METHODS: Tumor samples from 147 radically-treated breast cancer patients were studied immunohistochemically for Fas/Fas-ligand expression. RESULTS: Both Fas and Fas-ligand expression in the primary tumor were considerably less frequent among breast cancer patients with bone metastases compared to women without skeletal spread. Moreover, negative staining for Fas or the lack of Fas-ligand expression proved to be significant predictors for the survival free from bone metastases under univariate analysis. CONCLUSION: Our results suggest that the probability of bone metastases may be assessed on the basis of Fas/Fas-ligand expression in primary breast cancer. Consequently, their determination seems crucial for further prognosis and determination of adjuvant treatment. PMID- 17352236 TI - Bcl-2 expression in breast cancer: a comparative study at the mRNA and protein level. AB - BACKGROUND: Bcl-2 is one of the most important antiapoptotic genes. Although it facilitates the survival of tumor cells, its expression has been consistently associated with a better prognosis for breast cancer. Virtually all studies on Bcl-2 conducted in breast cancer have been carried out by means of immunohistochemistry. The aim of this study was to examine for the first time the expression of Bcl-2 in a series of human breast cancer, both at the mRNA and protein level. MATERIALS AND METHODS: One hundred samples from previously untreated human breast cancers were used; Bcl-2 expression was determined both by means of immunohistochemistry using the bcl-2/100/D5 monoclonal antibody and differential RT-PCR. Additionally, the expression of hormone receptors (ER and PR), c-erb-B2, p53 and the proliferation-associated Ki-67 antigen were also studied by means of immunohistochemistry as part of the standard pathological workup. RESULTS: Any degree of immunohistochemical staining correlated significantly and inversely with c-erb-B2 expression (p = 0.0008), nuclear grade 3 (p = 0.0015), a Ki-67 labeling index > 10% (p = 0.02) and tumor size (p = 0.048), and in a direct fashion with estrogen (p = 0.0003) and progesterone receptor expression (p = 0.0002). mRNA expression of the Bcl-2 gene showed a significant inverse correlation with c-erb-B2 (p = 0.016) and p53 (p = 0.014) expression, as well as with a nuclear grade 3 (p = 0.006), and a direct correlation with estrogen (p = 0.0004) and progesterone (p = 0.001) receptor expression, as well as with nodal invasion (p = 0.04). CONCLUSION: The study of Bcl-2 expression in breast cancer by means of either immunohistochemistry or RT PCR yields very similar results. In spite of its role opposing tumor cell death, Bcl-2 is associated with biological features of the tumors which define a better intrinsic prognosis, such as hormone receptor expression, low proliferation and absence of c-erb-B2 and mutant p53 expression. This may in great part explain why Bcl-2 expression has been invariably found to correlate with a better prognosis of breast cancer. PMID- 17352237 TI - Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro. AB - Mistletoe extracts are widely used in complementary and alternative cancer therapy in Europe. The extracts possess cytotoxic, as well as immunostimulatory effects. However, some investigators have suggested that low doses of mistletoe extracts could also induce tumor growth. The mistletoe extracts Helixor A, Helixor M and Helixor P were investigated for growth inhibitory and stimulatory effects in a panel of 38 human tumor cell lines in vitro. Mistletoe lectin I (ML 1), adriamycin and interleukin-6 (IL-6) were used as reference compounds. All three mistletoe preparations showed cytotoxic activity [T/C (Test/Control) < 30%]: Helixor P was the most potent, followed by Helixor M and Helixor A with IC50 (50% inhibitory concentration) values of 68.4, 114 and 133 microg/ml, respectively. The IC50 values of ML-1 and adriamycin were 0.026 and 0.069 microg/ml. None of the human tumor cell lines in the panel showed growth stimulation (T/C (Test/Control) > 125%) by the mistletoe extracts or ML-1, apart from two exceptions in the colon carcinoma cell line HCC-2998, in which Helixor M and ML-1 showed a marginal stimulation (TIC 128% and 131%, respectively) at one concentration only. Further investigations into the latter effect of Helixor M and ML-1 in the HCC-2998 line using five different proliferation assays, modified cell culture conditions and the identical production charge of mistletoe extract, as well as a new one, did not confirm the previous observation. It was concluded that the marginal stimulation found in the earlier experiments was a statistical coincidence. Helixor mistletoe preparations and ML-1 have cytotoxic activity and do not stimulate tumor cell proliferation in vitro which is in accordance with previous scientifically based observations on aqueous mistletoe extracts. PMID- 17352238 TI - CASC2a gene is down-regulated in endometrial cancer. AB - BACKGROUND: Chromosome 10q25-q26 has been strongly correlated to endometrial tumorigenesis. A novel human gene, CASC2, has previously been identified at chromosome 10q26. One out of the three alternative transcripted forms, CASC2a, has been demonstrated to be mutated at a low frequency in endometrial cancer (EC). In this study, the role of the CASC2a gene in cancer has been further defined. MATERIALS AND METHODS: Tumour and corresponding normal tissues were analysed for CASC2a mRNA expression by real-time RT-PCR and mutation status by PCR-based approaches. RESULTS: A significantly decreased level of CASC2a transcripts was observed in 13/17 (76%) EC tissues, as well as in 6/9 (67%) colorectal cancers. Exogenous expression of CASC2a in undifferentiated AN3CA endometrial cancer cells inhibited cellular growth in anchorage-independent growth assays. Finally, infrequent CASC2a mutations were able to impair the gene function. CONCLUSION: Altogether, our findings strongly suggest that CASC2a may act as a tumour suppressor gene, with both epigenetic and genetic alterations concurring to gene inactivation. Down-regulation of CASC2a may provide a growth advantage in EC cells. PMID- 17352239 TI - Involvement of Tiam1 in apoptosis induced by bufalin in HeLa cells. AB - BACKGROUND: It has been previously demonstrated that bufalin, an active agent in the Chinese medicine chan'su, induces apoptosis in human leukemia cells by altering the expression of apoptosis-related genes, such as bcl-2 and c-myc. Tiam1 was also found to play a critical role in bufalin-induced apoptosis through the activation of the Rac1, PAK and JNK pathway in human leukemia cell lines. In the present study, the involvement of the Tiam1 gene products in bufalin-induced apoptosis in human solid tumor HeLa cells was examined. MATERIALS AND METHODS: HeLa cells were treated with 10(-8) M bufalin and apoptosis was measured by ELISA quantification of nucleosomes. Tiam1 mRNA levels were quantified by real-time PCR analysis and inhibited by transfected siRNA specific for Tiam1. RESULTS: Apoptosis was induced in HeLa cells by treatment with 10(-8) M bufalin. Expression of both Tiam1 mRNA and its protein was induced 0.5 h after the start of the bufalin treatment. Transfection of Tiam1-specific siRNA into HeLa cells markedly inhibited bufalin-induced apoptosis. CONCLUSION: Our results suggest that Tiam1 is a downstream mediator of bufalin-induced apoptosis in the human solid tumor HeLa cell line, as well as in leukemia cell lines. PMID- 17352240 TI - Expression of type 2 hexokinase and mitochondria-related genes in gastric carcinoma tissues and cell lines. AB - BACKGROUND: The constant overexpression of glycolysis and active mitochondrial function are critical for productive energy required for the immortal proliferation of cancer cells. The genes related to glycolysis and mitochondrial respiration might have some function during stomach carcinogenesis. MATERIALS AND METHODS: The expression of hexokinase 2 (HK2), Bcl-2 and several mitochondria related gene products were investigated by immunohistochemistry in 257 consecutive human gastric carcinomas, and the results were compared with the clinicopathological characteristics. In addition, transcriptional change of HK2 and Bcl-2 was investigated in the hypoxic state or with mitochondrial inhibitors. RESULTS: In immunohistochemical analysis, HK2 was overexpressed in 43 out of 257 stomach cancer patients. Bcl-2 was not expressed in cases with HK2 positive cancer tissues except for one case, while the voltage-dependent anion channel, complex II and pyruvate dehydrogenase, located in mitochondria, were expressed in all cases. The patients with HK2 expression showed a worse prognosis compared to the HK2 negative cases, and patients who were negative in Bcl-2 and positive in HK2 represented the lowest survival rate. HK2 and Bcl-2 responded to hypoxia, but not to mitochondrial dysfunction while the cellular growth was severely repressed by mitochondrial inhibitors, indicating that transcriptional regulation of HK2 and Bcl-2 proceeds upstream of dysfunctional mitochondria. CONCLUSION: HK2 was overexpressed in 16.7% of gastric carcinomas, and reciprocal expression pattern with Bcl-2. The HK2 positive cases showed a worse prognosis and aggressive character. PMID- 17352242 TI - Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6. AB - BACKGROUND: Cancerous ovarian tissues contain and produce high levels of pro inflammatory cytokines (IL-1, IL-6 and TNF-alpha). The aim of this study was to assess the mechanisms by which autocrine IL-6 affects the ovarian carcinoma continuous cell line (SKOV-3) tumorigenicity. MATERIALS AND METHODS: Autocrine IL 6 was neutralized by the addition of anti-IL-6 antibodies to SKOV-3 cell cultures. The proliferation rate was evaluated by MMT staining and the capacity to produce matrix metalloproteinases (MMPs) 2 and 9 was examined by zymography. RESULTS: The SKOV-3 cells secreted IL-6 in a time-dependent manner (24-96 h). The addition of anti-IL-6 antibodies to SKOV-3 cell cultures did not affect their proliferation rate within 96 h of incubation. In addition, SKOV-3 cells secreted MMP-2 and MMP-9 as confirmed by zymography. The MMP-9 levels decreased in a time dependent manner (3, 8, 24 h) and the addition of anti-IL-6 antibodies to SKOV-3 cell cultures significantly decreased their capacity to secrete MMP-9, particularly after 8 h of incubation. MMP-2 (pro-active and active forms) was also secreted by SKOV-3 cell cultures but could be measured only after 24-96 h of incubation. The levels of MMP-2 increased in a time-dependent manner. The addition of anti-IL-6 antibodies to SKOV-3 cell cultures did not affect their capacity to secrete MMP-2. CONCLUSION: Our results suggest that IL-6 secreted by SKOV-3 cells could be involved in their tumorigenic potential, particularly potentiating their capacity to secrete MMP-9. PMID- 17352241 TI - Maspin expression was involved in colorectal adenoma-adenocarcinoma sequence and liver metastasis of tumors. AB - BACKGROUND: Maspin, a serine protease inhibitor related to the serpin family, can inhibit invasion and metastasis of malignancies. This study aimed to explore the roles of maspin expression in the tumorigenesis and progression of colorectal adenocarcinoma (CRA). MATERIALS AND METHODS: Maspin expression was examined on tissue microarrays containing CRAs (n = 119), adjacent adenoma (n = 22), adjacent non-cancerous mucosa (n = 118) and metastases (n = 67) by immunostaining. Microvessel density (MVD) was determined after labeling with anti-CD34 antibody using immunnostaining. The maspin expression was compared with clinicopathological parameters of the tumors, including expression of p53, Ki-67 and tenascin, MVD, and survival data. RESULTS: Maspin expression showed significant increase from colorectal non-cancerous mucosa to adenocarcinoma through adenoma (p < 0.05). Maspin expression correlated negatively with liver metastasis of CRA (p < 0.05), positively with tenascin expression (p < 0.05), but not with tumor size, depth of invasion, local invasion via vessels, lymph node metastasis, differentiation, expression of Ki-67 and p53 or MVD (p > 0.05). Maspin expression in the metastases of CRA was significantly consistent with their corresponding primary foci (p < 0.05). Kaplan-Meier analysis revealed no significant relationship between maspin expression and survival time of carcinoma patients (p > 0.05). CONCLUSION: Up-regulated maspin expression was involved in colorectal adenoma-adenocarcinoma sequence. Low maspin expression is closely linked to the liver metastasis of CRA possibly through degradation of the extracellular matrix-tenascin to enhance carcinoma cell mobility. PMID- 17352243 TI - Seliciclib (CYC202; r-roscovitine) in combination with cytotoxic agents in human uterine sarcoma cell lines. AB - BACKGROUND: Inhibition of cyclin-dependent kinases (CDKs) has recently emerged as an interesting approach to treat human malignancies. This was explored in human leiomyosarcoma (LMS) lines, which represent a tumour associated with poor survival, chemo-unresponsiveness and deregulation of cell cycle components. MATERIALS AND METHODS: Using isobologram analysis with MTT chemosensitivity testing, the effects of the CDK inhibitor seliciclib (CYC202, R-roscovitine) when used alone or in combination with paclitaxel was studied in uterine cancer cell lines. Apoptotic endpoints were also examined via Annexin V assay using flow cytometry and Western blotting. RESULTS: Overall seliciclib combined with paclitaxel proved synergistic for all cell lines. This was concomitant with an enhanced apoptotic effect and downregulation of the LAP survivin. CONCLUSION: Our data support the use of seliciclib as part of combination therapy for uterine cancer. PMID- 17352244 TI - Prognostic factors in Hungarian breast cancer patients. AB - BACKGROUND: Breast cancer is the most common cancer among women, with variable outcomes, justifying a continuous search for new parameters to predict accurate prognosis and indicate suitable adjuvant therapy for patients. MATERIALS AND METHODS: Fourty-four stage I-III breast cancer specimens were investigated immunohistochemically for the expression of cyclooxygenase-2 enzyme (COX-2), hormone receptors, tumor suppressor gene p53, oncogene HER2 and proliferation marker Ki-67. Additionally, twelve specimens were also investigated for the presence of the phosphorylated extracellular signal-regulated kinase (pERK). RESULTS: It was demonstrated that expressions of biological markers were related to each other (ER to p53 and Ki-67, COX-2 to ER, PgR, Ki-67 and p53, Ki-67 to p53 and PgR, p53 to PgR). CONCLUSION: Our data indicate that concomitant immunohistochemical evaluation of cyclooxygenase-2, hormone receptors, p53 and Ki 67 may be of clinical value in determining an accurate prognosis. PMID- 17352245 TI - Relation between human papillomavirus positivity and p16 expression in head and neck carcinomas--a tissue microarray study. AB - Overexpression of p16 has been demonstrated to be strongly related to the presence of HPV16, 18. Squamous cell carcinoma of the head and neck has been shown to be associated with human papillomavirus (HPV) infection. The main aim of this study was to investigate the relationship between HPV presence and p16 expression in a representative collection of 60 head and neck carcinomas by tissue microarrays. The presence of HPV (HPV6, 11-low risk, HPV16, 18-high risk) was detected by applying in situ hybridisation. P-16 protein expression was detected immunohistochemically. HPV6, 11 positivity was observed in 10 out of 60 carcinomas. HPV16, 18 presence was found in 30 out of 60 tumours. P-16 expression was detected in 35 out of 60 tumours. A statistically significant relationship was demonstrated between HPV16, 18 presence and increased expression of p16. Also the HPV6, 11 presence was significantly correlated with p16 immunoreactivity. Additionally, this study demonstrates that it is possible to analyse p16 expression and HPV presence by tissue microarrays. PMID- 17352246 TI - Ascorbic acid induces apoptosis in adult T-cell leukemia. AB - BACKGROUND: Adult T-cell leukemia (ATL) is an acute malignancy of activated T cells caused by the human T-cell lymphotrophic virus type-1 (HTLV-1). MATERIALS AND METHODS: The effects of non-cytotoxic concentrations of ascorbic acid (AA) were evaluated against HTLV-1 positive and negative cells. The effect of AA on apoptosis and proliferation was evaluated by cell cycle analysis. The role of p53, p21 Bax and Bcl-2a on cell cycle modulation and apoptosis was also assessed. The anti-proliferative effects were tested by determining the changes in the expression of transforming growth factors (TGF-alpha, TGF-beta1 and TGF-beta2). RESULTS: Ascorbic acid was found to reduce the proliferation of cells and induce apoptosis by the modulation of p53, p21, Bcl-2 and Bax. CONCLUSION: The results of this study show the anti-proliferative effects of AA against leukemic cells. PMID- 17352247 TI - Antitumor efficacy of the cytotoxic RNase, ranpirnase, on A549 human lung cancer xenografts of nude mice. AB - BACKGROUND: The cytotoxic RNase, ranpirnase (ONCONASE, ONC), may have promising therapeutic implication as an alternative for cisplatin for the treatment of lung cancer, due to inhibition of protein synthesis by t-RNA cleavage. MATERIALS AND METHODS: A549 and NCI-H1975 human NSCLC cell lines were cultured in the presence and absence of ONC. Cytotoxicity was monitored using a clonogenic assay. Using an inverted phase and fluorescence microscope, we studied whether apoptosis was induced by ONC in gefitinib-induced apoptosis-resistant A549 tumor cells. The therapeutic effectiveness of ONC was studied via single and multiple administrations on A549 human non-small cell lung cancer (NSCLC), including tumors previously untreatable by cisplatin. ONC-induced changes in ATP levels were also monitored by non-localized phosphorus MR spectroscopy. RESULTS: ONC significantly inhibited the cell growth of A549 tumors. Apoptosis was significantly induced by ONC in a dose-dependent manner. In animal studies, multiple small doses of ONC were more effective than one large single dose for the inhibition of tumor growth with reduced side-effects, probably due to the normalization of leaky tumor vessels. ONC in combination with cisplatin significantly reduced tumor growth of A549 tumors. In large tumors, including those unsuccessfully treated with cisplatin, ONC showed inhibition of tumor growth, while a second treatment of cisplatin did not. During monitoring by non localized phosphorus MR spectroscopy, ATP levels decreased, likely due to ONC induced inhibition of oxygen consumption (QO2). CONCLUSION: ONC significantly inhibited tumor growth of A549 NSCLC cells in both in vitro and in vivo studies. This investigation suggests important potential clinical uses of ONC for the treatment of NSCLC cancer patients. PMID- 17352248 TI - Inhibition of angiogenesis via FGF-2 blockage in primitive and bone metastatic renal cell carcinoma. AB - BACKGROUND: Fibroblast growth factor-2 (FGF-2) has a role in the angiogenesis induced by renal carcinoma. MATERIALS AND METHODS: Blockage of FGF-2 by an antisense oligonucleotide (ASO) or by a mouse neutralizing anti-human FGF-2 monoclonal antibody (anti-FGF-2-mAb) was evaluated on a cell line isolated from a renal carcinoma bone metastasis (CRBM-1990), on Caki-1 and ACHN cells. Cocultures of endothelial cells and ASO- or mAb-treated carcinoma lines were investigated. RESULTS: Anti-FGF-2-mAb treatment induced a 33% reduction of FGF-2 released by ACHN, a 31% reduction of FGF-2 released by Caki-1, and a 70% reduction of FGF-2 released by CRBM-1990. ASO treatment did not inhibit endothelial cell proliferation. In contrast, anti-FGF-2-mAb significantly decreased endothelial cells proliferation induced by ACHN and CRBM-1990. The inhibition of endothelial cell growth was reverted by recombinant FGF-2. CONCLUSION: Modulation of FGF-2 production by renal cell carcinoma with a blocking mAb produced a significant inhibition of endothelial cell growth. PMID- 17352249 TI - In vitro histoculture drug response assay and in vivo blood chemistry of a novel Pt(IV) compound, K104. AB - BACKGROUND: The newly synthesized octahedral Pt(IV) complex series showed potent antitumor activities, both in vitro and in vivo. Carboplatin, possessing a soluble leaving ligand, is known to be less toxic than cisplatin. The synthesized K104 is a Pt(IV) complex with a malonato leaving group and seven-membered ring structure between the central platinum and amine carrier ligands. In this study, the histoculture drug response assay (HDRA) of K104 on human cancer tissues was investigated in vitro and nephrotoxicity was examined in vivo. MATERIALS AND METHODS: Cytotoxicity was tested in various cancer cell lines, and the HDRA of K104 was evaluated by MTT assay in vitro using colorectal and breast cancer tissues from patients. In order to compare the nephrotoxicity of K104 with cisplatin and carboplatin, blood serum levels of BUN, creatinine and uric acid in ICR mice were measured. RESULTS: K104 showed more effective anticancer activities than carboplatin in most cancer cell lines. In HDRA, K104 showed a 50.0-66.7% efficacy rate compared with 33.3% of cisplatin and 58.3% of carboplatin against colorectal cancer patient tissues. In breast cancer tissues, K104 only showed an efficacy rate above 50%. The serum levels of BUN, creatinine and uric acid did not change after a single intraperitoneal administration of K104 (90 mg/kg) in ICR mice. CONCLUSION: K104 showed more effective anticancer activities than carboplatin. Cisplatin was associated with nephrotoxic effects, but K104 did not change the serum levels of BUN, creatinine and uric acid in vivo. These results suggest that K104 is a promising anticancer agent in view of its high efficacy against human solid cancer and lower toxicity in vivo. PMID- 17352250 TI - NF-kappaB-independent induction of endothelial cell apoptosis by the vascular disrupting agent DMXAA. AB - BACKGROUND: DMXAA (5,6-dimethylxanthenone-4-acetic acid; AS1404), a vascular disrupting agent currently in clinical trials, induces tumour endothelial cell apoptosis in vivo in mice and in cancer patients. DMXAA activates NF-kappaB in many different cell types. In this study, whether DMXAA-induced endothelial cell apoptosis was NF-kappaB dependent was determined. MATERIALS AND METHODS: HUVEC endothelial and T24 endothelial-like cells were treated with DMXAA and apoptosis was measured by terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL). NF-kappaB activation was measured by electrophoretic mobility shift assays (EMSA). T24 cells were transfected with IkappaBalphaM, a mutant form of the IkappaBalpha gene which cannot be phosphorylated and degraded, hence preventing NF-kappaB expression. RESULTS: No NF-kappaB up-regulation was detected in apoptotic HUVEC treated with DMXAA. The IkappaBalphaM-transfected T24 cells showed similar apoptotic responses to those of parental cells. CONCLUSION: The DMXAA-induced apoptosis is neither mediated by, nor inhibited by, the expression of the NF-kappaB pathway. PMID- 17352251 TI - Prognostic significance of metallothionein, p53 protein and Ki-67 antigen expression in laryngeal cancer. AB - BACKGROUND: This study aimed at the evaluation of the expression of metallothionein (MT) in laryngeal carcinoma and its correlation with the expression of Ki-67 antigen and p53 protein and selected clinical and pathological variables in view of their potential prognostic significance. MATERIALS AND METHODS: Sixty-five laryngeal cancer patients were retrospectively analysed. Expression of MT, Ki-67 and p53 in tumour tissue samples were assessed by immunohistochemistry. RESULTS: In laryngeal cancer a significantly augmented expression of MT, Ki-67 and p53 was noted, as compared to the control group (p < 0.001) and a significantly increased expression of MT in low malignancy tumours (G1) as compared to the control group (p < 0.001). The expression of Ki-67 antigen was positively correlated with the expression of p53 protein (r = 0.477; p < 0.05) and expression of either marker was positively correlated with malignancy grade (r = 0.47, p < 0.05; r = 0.31, p < 0.05; for Ki-67 and p53, respectively). Shortened survival was noted in patients with high expression of Ki-67 antigen and p53 protein. CONCLUSION: The intensity of MT expression was not related to prognosis in laryngeal cancer. Nevertheless, it may provide a significant index indicating the malignant transformation of benign lesions of laryngeal epithelium. PMID- 17352252 TI - (2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide induces apoptosis and cell cycle arrest in HL-60 cells. AB - BACKGROUND: Ferulic acid is one of the most ubiquitous phenolic compounds in nature, which has antioxidant and anticancer activities. However, ferulic acid derivatives, such as ferulamide have never been reported. MATERIALS AND METHODS: (2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide (compound 8), a ferulamide derivative was synthesized in our laboratory. In this study, HL-60 cells were treated with various concentrations of compound 8, and its effects on cell growth, cell cycle, apoptosis and related measurements were investigated. RESULTS: Compound 8 inhibited cell growth in a concentration- and time-dependent manner with significant cytotoxicity, and the concentration required to inhibit growth by 50% (IC50) was 8.2 microM for 24 h. The cell cycle analysis indicated that compound 8 treated cells were arrested in the G2/M-phase and followed by apoptosis. Microscopic examination showed that treatment with compound 8 displayed typical morphological features of apoptotic cells, with cell shrinking and formation of apoptotic bodies. Reverse transcription-polymerase chain reaction (RT- PCR) analysis showed a dramatic induction of CDK inhibitor p21, which inhibited the expression of cyclin B1, thereby resulting in G2/M phase arrest. After G2/M-phase arrest, cells underwent apoptosis via significant down regulation of Bcl-2 expression. CONCLUSION: These results enhance our understanding of the mechanisms of action of compound 8-mediated anticancer effects. PMID- 17352253 TI - Modulatory effects of heparin on cellular accumulation and cytotoxicity of doxorubicin in MRP1-overexpressing HL60/doxo cells. AB - BACKGROUND: The overexpression of multidrug resistance protein (MRP1), associated with high levels of intracellular glutathione (GSH), is a well characterized mechanism of multidrug resistance (MDR) in several malignancies. Various chemosensitizers have been used in vitro to modulate the MRP1 activity, but the high toxicity limits their clinical application. Unfractionated heparin (UFH), is frequently used to prevent thrombo-embolic complications in cancer patients. This in vitro study aimed to elucidate the potential role of UFH as a sensitizer in anticancer clinical chemotherapy. MATERIALS AND METHODS: The human leukemic doxorubicin-resistant cell line (HL60/doxo), which overexpresses the MRP1 protein was treated with UFH alone or in combination with three different concentrations of doxo. The intracellular accumulation and cytotoxicity of doxo and the cellular GSH content were measured in comparison with the leukotriene LTD4 receptor antagonist, MK571, a specific MRP1 inhibitor. RESULTS: UFH increased doxo accumulation and cytotoxicity in the HL60/doxo cell line with respect to cells treated with doxo alone. UFH also decreased the cellular GSH content in the HL60/doxo cells with respect to the control, suggesting a potential involvement of UFH in doxo co-transport with GSH. CONCLUSION: Our results demonstrate that UFH modulates MRP1-mediated MDR in HL60/doxo cells expressing high MRP1 levels. These findings suggest a potential clinical application of heparin as an adjuvant to overcome MRP1-mediated drug resistance in cancer patients. PMID- 17352254 TI - Inhibition of breast cancer cell proliferation by style constituents of different Crocus species. AB - Among the different species of Crocus, only C. sativus has been extensively studied for the composition and the biological properties of its styles, since these constitute the well-known spice saffron, which is widely used in the Mediterranean, Indian and Chinese diet. With high performance liquid chromatography (HPLC) and UV/vis spectroscopy, the presence of hydrophilic carotenoids in the styles of three other Crocus taxa, endemic in Greece, C. boryi ssp. tournefortii, C. boryi ssp. boryi and C. niveus, is reported for the first time. Incubation of MCF-7 and MDA-MB-231 breast cancer cells for 48 h with different concentrations of all four Crocus style extracts showed a dose dependent inhibitory effect on cell proliferation measured by the MTT assay. The antiproliferative effect was not related to the presence of estrogen receptors. Studies on the effect of trans-crocin-4 (the main carotenoid constituent of C. sativus styles, digentibiosylester of crocetin), crocetin and safranal showed that the antiproliferative effect is attributed to the constituent crocins irrespective of the degree of glycosylation. These results show that the styles of the various Crocus taxa merit further investigation of their composition and mechanisms of action of their carotenoid constituents in order to establish if they could be used as chemopreventive or anticancer agents. PMID- 17352255 TI - Comparative cytotoxicity and ROS generation by curcumin and tetrahydrocurcumin following visible-light irradiation or treatment with horseradish peroxidase. AB - In order to clarify the cytotoxic mechanism of curcumin, a well-known chemopreventive agent, the cytotoxicity (by MTT method), intracellular glutathione (using GSH detection kit) and intracellular reactive oxygen species (ROS) levels (with a flow cytometer), were measured in curcumin- and tetrahydrocurcumin (TH-curcumin)-treated cancer (HSG) and normal (HGF) cells under two different oxidation conditions: irradiation with visible light (VL) and enzymatic oxidation with horseradish peroxidase (HRP)/H2O2. The cytotoxicity of curcumin was highly enhanced by VL-irradiation, whereas that of TH-curcumin was enhanced by HRP/H2O2 treatment. The cytotoxicity of curcumin against HGF cells was greater than that against HSG cells. Curcumin significantly reduced the intracellular GSH level significantly under VL-irradiation, and increased it under HRP/H2O2, whereas TH-curcumin had no effect with either oxidation treatment. HRP/H2O2 treatment of TH-curcumin enhanced generation of ROS; in contrast, VL-irradiation of curcumin was considered to produce ROS preferably. In conclusion, curcumin was highly photo-toxic, caused a decrease in GSH and mediated ROS generation. In contrast, the cytotoxicity of TH-curcumin was enhanced by enzymatic oxidation. A low-level pro-oxidant intracellular milieu induced by TH-curcumin could be effectively useful for cancer prevention. PMID- 17352256 TI - A role for DHX32 in regulating T-cell apoptosis. AB - DHX32 is a novel putative RNA helicase with an activation-dependent pattern of expression in T-cells. To gain insight into the role of DHX32, Jurkat-DHX32 cells, a stable Jurkat T-cell line with constitutive DHX32 expression, were generated by retroviral gene transfer. There were no significant differences between control and Jurkat-DHX32 cells in terms of proliferation and response to several chemotherapeutic agents. There was an altered response of Jurkat-DHX32 cells to Fas signaling associated with down-regulation of the anti-apoptotic protein c-FLIP short. In normal peripheral blood lymphocytes, a correlation between DHX32 and c-FLIP short expression was detected in response to different T cell specific and non-specific activation stimuli. Our results suggest that DHX32 might be involved in regulating T-cell response to certain apoptotic stimuli. PMID- 17352257 TI - The role of Ca+2 on rhein-induced apoptosis in human cervical cancer Ca Ski cells. AB - Apoptosis induced by rhein, an active component of senna, has been reported in various human cancer cells, however, its molecular mechanisms are not precisely known. In this study, the mechanisms of apoptosis by which rhein acts on human cervical cancer Ca Ski cells were examined. Flow cytometric analysis demonstrated that rhein induced the abrogation of mitochondrial membrane potential (MMP) and cleavage of Bid protein. Rhein also induced an increase in the levels of Fas, p53, p21 and Bar, but a decrease in the level of Bcl-2. The activities of both caspase-8 and -9 were enhanced by rhein, promoting caspase-3 activation, leading to DNA fragmentation, thus, indicating that rhein-induced apoptosis is caspase dependent. In addition, rhein induced an increase in the level of cytoplasmic Ca2+, which was inhibited by BAPTA (a calcium chelator). BAPTA attenuated the MMP abrogation and significantly dinimished the occurrence of rhein-induced apoptosis in Ca Ski cells. In conclusion, our data demonstrate that rhein-induced apoptosis occurs via a caspase-dependent and mitochondria-dependent pathway which is closely related to the level of cytoplasmic Ca2+ in Ca Ski cells. PMID- 17352258 TI - Mast cell and eosinophil interaction in gastric carcinomas: ultrastructural observations. AB - BACKGROUND: An increase in the number of mastocytes has been described in some human neoplasms, mainly in gastric and colorectal cancer. MATERIALS AND METHODS: A case of diffuse-type gastric carcinoma, mainly infiltrated by eosinophils and mast cells, was studied using light and electron microscopy. RESULTS: Using light microscopy, cell clusters containing one mast cell and one to three eosinophils were found in the tumour stroma. Electron microscopy of this unusual stromal element revealed that mast cells established areas of junctions with eosinophils. Moreover, focal polarized exocytosis of mast cell granules was found in the areas of junctions with eosinophils. Eosinophils in contact with mast cells showed signs of important in situ activation, such as alterations in the size and number of granules, cytoplasmic vacuoles, and scattered extracellular granules. CONCLUSION: Our ultrastructural study provides morphological evidence of cross talk between activated mast cells and eosinophils that may play an important role in the enhancement of host immunity against cancer cells. PMID- 17352260 TI - Primary cultured human breast epithelial cells up-regulate protein disulfide isomerase in response to zeranol. AB - BACKGROUND: Experimental data at the molecular, cellular and organismal levels have implicated dietary components in cancer. Exposure to numerous growth factors, hormones and environmental agents, that can regulate signaling events, is involved in carcinogenesis. Research targets on gene-nutrient interactions may give useful information for the development of a novel diet-based intervention for the at-risk population. MATERIALS AND METHODS: To examine the proteomic effect of a low level dietary compound on potential breast cancer, primary human breast epithelial cells were isolated and cultured in media with or without zeranol, an anabolic, non-estrogenic growth promoter with estrogenic activity, used in beef cattle and naturally found in some fungus in grain. The cells then underwent proteomic analysis. RESULTS: 2-D electrophoresis showed that protein disulfide isomerase (PDI) was up-regulated 5-fold in the breast epithelial cells exposed to zeranol. PDI has been shown to be up-regulated in a variety of cancerous tissues, although this is the first reported up-regulation of PDI in breast tissue. CONCLUSION: PDI may be a useful marker of dietary exposure to zeranol. PMID- 17352259 TI - Morin inhibits the growth of human leukemia HL-60 cells via cell cycle arrest and induction of apoptosis through mitochondria dependent pathway. AB - The effects of morin (3,5,7,20,40-pentahydroxyflavone) on human leukemia HL-60 cells in vitro were investigated and the molecular mechanisms of morin-induced G2/M arrest and apoptosis in HL-60 cells were examined. Morin induced morphological changes and decreased the percentage of viable cells via induction of G2/M-phase arrest and apoptosis. Morin-induced G2/M-phase arrest was accompanied by the promotion of p21 and Wee1, and decreased levels of Cdc25c and cyclins A and B1 complex. Morin-induced apoptosis in HL-60 cells was also confirmed by flow cytometric assay, DNA gel electrophoresis for DNA fragmentation and DAPI staining. Morin induced apoptosis in time- and dose-dependent manners. Morin-induced apoptosis was associated with elevated intracellular reactive oxygen species (ROS) increased and Ca2+ production; decreased the levels of mitochondria membrane potential (deltapsi(m)) and increased caspase-3 activation. Collectively, these results suggest that the morin-induced apoptosis in HL-60 cells may result from the activation of caspase-3 and intracellular Ca2+ release, as well as the mitochondria membrane potential pathway. PMID- 17352261 TI - Telomere length and telomerase activity in extra-abdominal desmoid tumors. AB - The telomere biology of extra-abdominal desmoids was investigated. In 12 specimens, telomere length was assessed by Southern-blot analysis and telomerase activity was measured using a PCR-based TRAP assay. There was a significant correlation between telomere length and tumor size, with telomeres being shorter with increasing tumor size (p = 0.049), and between telomere length and PCNA positive cell rate, with telomere shortening with increased positive cell rate (p = 0.017). There was a significant correlation between telomerase activity and age at surgery, with increased activity with younger age (p = 0.015). Telomere length increased with recurrence, but telomerase activity decreased, and rate of PCNA positive cells became lower, whenever the tumors were recurrent. Decreasing telomere length correlated with tumor size, probably due to increased duration of proliferation in the tumor, and tumor aggressiveness. Recurrent case results may be due to a lower rate of cell division and the presence of telomerase activity. PMID- 17352262 TI - Pharmacokinetics of albendazole in New Zealand white rabbits: oral versus intraperitoneal administration. AB - BACKGROUND: Recent studies from our group have shown the potent antitumor effects of albendazole (ABZ). It was hypothesized that intraperitoneal (i.p.) administration of ABZ in peritoneal carcinomatosis (PC) could lead to long exposure of tumor cells to high concentration of the drug and possibly to reduced systemic toxicity. MATERIALS AND METHODS: Eight male New Zealand white rabbits were randomized into two groups, all given a single dose of ABZ 150 mg/kg suspended in 0.5% carboxymethylcellulose (CMC), either as i.p. injection, or as oral administration. The concentration of ABZ and its metabolites in plasma were determined using a high performance liquid chromatography method. RESULTS: The parent drug was detected in plasma after oral and i.p. administration. The C(max) of albendazole sulphoxide (ABZ-SO) resulted in a much higher plasma concentration in the oral group (41.86 microg/ml) than in the i.p. group (16.84 microg/ml, p < 0.05). The area under the concentration over time curve of ABZ-SO in the oral group (1010.43 microg/ml/h) was also significantly higher than that of the i.p. group (528.33 microg/ml/h, p < 0.05). Compared to oral administration, the i.p. administration of an ABZ suspension led to significantly lower plasma levels of the major metabolite (ABZ-SO). This could have considerable therapeutic benefits in the regional treatment of PC. PMID- 17352263 TI - Imatinib mesylate inhibits tumorigenicity of malignant fibrous histiocytoma cells in vivo. AB - BACKGROUND: Malignant fibrous histiocytoma (MFH) is one of the most diffuse and aggressive tumors among soft tissue sarcomas in adults, but still poorly characterized from the molecular viewpoint. MFH cell proliferation is inhibited selectively by imatinib mesylate, a tyrosine kinase inhibitor. The expressions of platelet-derived growth factor receptors (PDGFRs) and c-Kit have been previously examined in MFH cell lines and the inhibitory effect of imatinib mesylate on the MFH cell proliferation was tested. MFH cell lines showed various patterns of PDGFRs and c-Kit expression. Imatinib mesylate inhibited the proliferation of MFH cells that expressed PDGFRs and/or c-Kit. MATERIALS AND METHODS: Four MFH cell lines were used (Nara H, Nara F, GBS-1 and TNMY1). The mRNA expression of PDGFRs and c-Kit was analyzed using RT-PCR; cell proliferation was analyzed using the MTS assay. Immunohistochemistry was used to analyze the inhibitory effect of imatinib mesylate on phosphorylation of PDGFRs and c-Kit in vivo. The Nara H and TNMY1 cell lines were implanted into nude mice and tumor growth was evaluated daily by measuring the two-dimensional diameters of the tumor nodule. RESULTS: PDGFRs and c-Kit were expressed in Nara F, GBS-1 and TNMY1, but not in Nara H cells. Imatinib mesylate inhibited PDGFRs and c-Kit phosphorylation in TNMY1 cells affecting the tumorigenicity, in the control group (139 mm3 SD +/- 1.03) and treatment group (126.2 mm3 SD +/- 1.63) but did not affect the tumorigenicity of Nara H cells. CONCLUSION: Imatinib mesylate reduced in vivo tumor growth of MFH that express PDGFRs and c-Kit associated with phosphorylation suppression. PMID- 17352264 TI - Biodistribution and radioimmunotherapy of SCCHN in xenotransplantated SCID mice with a 131I-labelled anti-EpCAM monoclonal antibody. AB - BACKGROUND: The mortality from squamous cell carcinoma of the head and neck (SCCHN) remains high and almost unchanged throughout the last decades. Therefore, new therapeutic strategies are urgently needed. One promising approach is the application of radio-labeled antibodies directed against tumor-associated antigens. EpCAM is a transmembrane protein, which is overexpressed on almost all SCCHN, making it a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to establish an animal model to investigate the biodistribution and the therapeutic effect of a radio-labeled EpCAM-specific monoclonal antibody (mAb). MATERIALS AND METHODS: The mAb C215 was labeled with 131I and tested for its antitumor effect against established SCCHN xenografts in SCID mice. Initially, the biodistribution of the mAb in the tumor and different organs was determined with a gamma counter and was calculated as % injected dose/gram tissue. For therapeutic approaches 5, 15 or 25 MBq 131I-labeled mAb was injected as a single bolus into tumor-bearing mice. Control animals received either sodium chloride or the unlabeled mAb. The tumor growth and body weight of the animals were measured at various times after administration of the antibody. RESULTS: Initially, high activity was seen in all organs after systemic administration of 13I-C215. Over time general activity decreased whereas an accumulation of activity was seen in the tumor. Tumor growth was delayed in the groups receiving either 15 MBq or 25 MBq 131I-C215 relative to control groups and the 5 MBq group. However, animals in the high-dose groups suffered from treatment related toxicity, which led to body weight loss of more than 20%. CONCLUSION: Our data demonstrate that the EpCAM-specific radio-labeled mAb C215 is a promising tool to target SCCHN leading to significant tumor control. Further studies are necessary to increase efficacy and reduce toxicity of this new therapeutic approach. PMID- 17352265 TI - Apoptosis in brain tumors: prognostic and therapeutic considerations. AB - The direct and indirect regulation, as well as the mechanisms of apoptosis in the nervous tissue and their implications in the treatment and prognosis of brain tumors are reviewed. PMID- 17352266 TI - Expression of high mobility group box chromosomal protein-1 (HMGB-1) in gastric cancer. AB - The intranuclear architectural protein termed high mobility group box chromosomal protein 1 (HMGB-1) has recently been identified as a potent proinflammatory mediator. The release of HMGB-1 results in the activation of macrophages and leads to an inflammatory response. In the tumor microenvironment, it is well known that there are local inflammatory reactions and the degree of inflammatory cell infiltration inside a tumor is correlated to the prognosis of the disease. In the present study, the expression of HMGB-1 in gastric cancer cells was evaluated in relation to the clinicopathological findings (n = 76), and its expression was analyzed in comparison to immune reactive cells in gastric cancer. The expression of HMGB-1 in gastric cancer cells with the intestinal type (90.7 positive cells per 200 cancer cells +/- 37.9, n = 40) was significantly increased compared to that in the diffuse type (56.8 +/- 32.7, n = 36) (p < 0.01). Secondly, HMGB-1 expression in gastric cancer cells was positively correlated with the degree of macrophage infiltration inside the tumor microenvironment (r = 0.869, p < 0.01). Thirdly, the prognosis of the low HMGB-1 group (n = 41) was significantly poorer than that of the high HMGB-1 group (n = 35, p < 0.05), although the HMGB-1 expression in cancer cells was not an independent prognostic factor. HMGB-1 expression may be one of the key factors regulating inflammatory reactions within the tumor microenvironment. PMID- 17352267 TI - Association of matrix metalloproteinase-1 (-1607 1G/2G) polymorphism with increased risk for oral squamous cell carcinoma. AB - BACKGROUND: The purpose of this study was to investigate the possible relation of matrix metalloproteinase-1 (MMP-1) to increased risk for oral cancer, in light of recently found contribution of angiogenesis and thrombosis-related factors to the development of malignancies. MATERIALS AND METHODS: The 1G/2G polymorphism in the MMP-1 gene, which influences its expression, was examined in 156 patients with oral squamous cell carcinoma and 141 healthy controls of comparable ethnicity (Greeks and Germans), gender and age. RESULTS: In comparison to controls, the detected 2G allele frequency was significantly lower in the patient group and in subgroups with early cancer stages, with positive family history of thrombophilia, with tobacco abuse and without alcohol abuse (p < 0.05). These findings were mainly due to a significant decrease in 2G/2G homozygotes despite a small increase in 1G/2G heterozygotes in the above groups. CONCLUSION: These findings suggest a significant involvement of the MMP-1 -1607 1G/2G polymorphism in the increasing risk for oral cancer in the 1G allele European carriers. PMID- 17352268 TI - Histone deacetylase inhibitors, but not vincristine, cooperate with radiotherapy to induce cell death in medulloblastoma. AB - BACKGROUND: Though ionising radiation (IR) is an efficient means of postoperative treatment for children with medulloblastoma, the disease is incurable in about a third of them. Thus, multimodality regimens have been introduced, typically combining IR with vincristine. MATERIALS AND METHODS: The combination of IR and vincristine was compared to the combination of IR and histone deacetylase inhibitors (HDIs) for their anticancer activity against medulloblastoma cells in vitro. Cytotoxic activities were assessed by measuring propidium iodide uptake and by cell cycle analysis. RESULTS: HDIs augmented the cytotoxic effect of IR, while the combination of vincristine and IR was significantly less cytotoxic than vincristine alone. Cell cycle analyses revealed that vincristine did not interfere with IR-induced G2/M arrest, whereas HDIs abolished the latter. CONCLUSION: These in vitro findings indicate a favourable interaction of IR and HDIs, but an unfavourable one of IR and vincristine, in medulloblastoma, and provide a rationale for comparing the combination of IR with either vincristine or HDIs in vivo. PMID- 17352269 TI - Pharmacokinetics of liposomal cisplatin (lipoplatin) in combination with 5-FU in patients with advanced head and neck cancer: first results of a phase III study. AB - BACKGROUND: Lipoplatin, a novel liposomal formulation of cisplatin, is composed of cisplatin and liposomes based on dipalmityl phosphatidyl glycerol (DPPG), soy phosphatidyl choline (SPC-3), cholesterol and methoxypolyethylene glycol distearoyl phosphatidylethanolamine (mPEG2000-DSPE). Liposomal encapsulation of cisplatin is designed to increase safety and tolerability by decreasing, e.g., nephrotoxicity through decreased exposure of organs to cisplatin, while effectively delivering the drug to the tumor. In an ongoing phase III trial comparing cisplatin to lipoplatin (both in combination with infusional high-dose 5-Fluoruracil) in advanced head and neck cancer (HNC), a sub-study to determine the pharmacokinetic profile of lipoplatin in comparison to conventional cisplatin was undertaken. MATERIALS AND METHODS: In total, twelve patients with advanced HNC received a combination chemotherapy with either lipoplatin/5-FU or cisplatin/5-FU. Plasma samples were analyzed for concentration of total platinum in patients from both arms. RESULTS: All twelve patients from the pharmacokinetic sub-study were male Caucasians at a mean age of 60 years. There was no difference in age or kidney function between the two treatment groups. The total body clearance for cisplatin was 1.25 L/(hxm2) for the liposomal formulation, compared to 0.62 L/(hxm2) for conventional cisplatin. The terminal half life was half as long for lipoplatin (10.98 h) as compared to cisplatin (24.5h). Even though the maximum observed concentration in the plasma (C(max) was greater for lipoplatin than for cisplatin, the area under the concentration time-curve (AUC) was less (6.5 microg/ml vs. 4.07 microg/ml and 66.85 microg/h/ml vs. 130.33 microg/h/ml, respectively). CONCLUSION: The pharmacokinetic profile of lipoplatin (in combination with 5-FU) suggests that the liposomal formulation results in a greater body clearance and shorter half life than conventional cisplatin, which confirms the clinical observation of decreased taxicity, especially renal deterioration. PMID- 17352270 TI - Similar patterns of loss of heterozygosity in serum of adenocarcinoma of the distal oesophagus and the cardia in early diagnosis. AB - BACKGROUND: Loss of heterozygosity (LOH) may be a valuable tool for detection of malignant proceedings. The aim of our study was to investigate LOH in the serum of patients with adenocarcinoma of the distal oesophagus and the cardia for diagnostic and prognostic utility. PATIENTS AND METHODS: Matched tumour and serum samples from 46 surgically treated patients with oesophageal adenocarcinoma and cardia carcinoma divided in two groups were analysed. Twelve markers were examined with a PCR-based microsatellite analysis. RESULTS: A similar high frequency of LOH (range from 77% to 96%) was detected in the tumour and serum of both groups, whereas no LOH was detected in 20 healthy individuals. However, no significant correlation between LOH incidence and clinicopathological characteristics and survival was found. CONCLUSION: The results indicate that DNA alterations in tumours of the oesophagus and cardia are uniform. The high frequency of LOH in tumour patients underlines the utility of this molecular approach as a diagnostic tool. PMID- 17352271 TI - [Recurrent pleomorphic adenomas of the parotid gland--treatment and outcome]. AB - Epithelial tumors of the parotid gland comprise 3% of head and neck tumors, and 70%-80% of those are benign. Pleomorphic adenoma is the most common tumor of the parotid gland. Recurrence rate of pleomorphic adenomas (RPAs) following superficial parotidectomy was reported to be as high as 4%, sometimes associated with inadequate surgical treatment of the primary tumor. These tumors have a very slow growth rate, and a ten-year follow-up period is mandatory. RPAs are usually located in the superficial lobe (75%) and are often multinodular. Treatment of RPAs is challenging due to a high risk of facial nerve paresis (7%-50%) and of re recurrence. Occasionally, post-operative radiotherapy is indicated, but this treatment must be balanced with potential long term risks of secondary malignancy. Medical records of 16 patients with first recurrence and 4 patients with more than one recurrence who were treated in our institution during the past 5 years were reviewed. Five patients were treated by post-operative radiotherapy. Residual or recurrence rate following a second procedure was 15%. Two patients (10%) had permanent paresis of a single branch of the facial nerve. Seventeen out of 20 patients (85%) treated were disease-free after a follow-up period of 5 years. In conclusion, surgical treatment of RPAs is a complex procedure which should be managed by a trained surgical team and can be performed with success and minimal morbidity. PMID- 17352272 TI - [Frontal sinus fractures: five years of treatment experience]. AB - BACKGROUND: Frontal sinus fractures are commonly encountered in major trauma centers. They are almost exclusively seen in young adults and are usually caused by high velocity impacts. The intimate association of the frontal sinuses with structures such as frontal lobes and the eyes makes the appropriate management of this injury essential. PURPOSE: To review patients that suffered from frontal sinus fractures and underwent surgery, and to evaluate the efficacy and complications of this treatment. METHODS: This is a retrospective study. The study population included all the patients that suffered from frontal sinus fracture and underwent a surgical intervention between the years 1998-2002. The data that was collected included demographic parameters, cause of injury, timing and kind of surgery, postoperative complications and patient satisfaction. RESULTS: A total of 47 patients were operated on due to frontal sinus fractures during the years 1998-2002. Only 38 had adequate follow-up. Seventy percent of the patients suffered from bitable fractures. The other 30% had only anterior wall fractures. A total of 47% of the patients had additional facial fractures and 39% had intracranial injuries. Most of the patients were operated on during the first 24 hours (50%). The incidence of major postoperative complications was 2.5% (1 patient had meningitis). Minor complications occurred in 15% of the patients (mainly decreased forehead sensation). CONCLUSIONS: Frontal sinus fractures are commonly seen in major trauma centers. High index of suspicion, careful physical examination and imaging assistance are essential for accurate diagnosis. Lack of appropriate treatment can lead to serious intracranial complications. The surgical intervention achieves good cosmetic and functional outcomes in a majority of the patients. PMID- 17352273 TI - [Varicella zoster virus infection involving the maxillary branch of the trigeminal nerve]. AB - Herpes zoster is an infection caused by reactivation of the latent varicella virus in the sensory ganglia. The mechanisms responsible for Varicella zoster virus (VZV) reactivation are poorly understood. Yet, it is believed that decreased cellular immunity can be a trigger for it's reactivation. The occurrence of herpes zoster in young people may point to an underlying immunodeficiency. Therefore, the possibility of concomitant HIV infection must be eliminated. Herpes zoster manifests as a vesicular rash along a sensory dermatome, usually preceded by pain or paresthesia of the involved cutaneous area. The most commonly affected dermatomes are those of the thorax and abdomen, followed by the cranial nerves, especially the trigeminal nerve. The maxillary nerve is the least frequently affected branch of the trigeminal nerve and only rarely causes ocular injury. This is a case history of a young patient infected with VZV involving the maxillary branch of the trigeminal nerve, complicated by secondary bacterial infection of the ipsilateral hemiface. The literature regarding the epidemiology, pathogenesis, complications and the proper treatment of herpes zoster is reviewed with an emphasis on the involvement of cranial nerves. PMID- 17352274 TI - [Bilateral vocal cord paralysis due to rheumatoid arthritis]. AB - Cricoarythenoid arthritis can be part of rheumatoid arthritis, which can present with laryngeal symptoms as in other systemic diseases. Bilateral vocal cord paralysis can developed with the progression of cricoarythenoid arthritis and can endanger the patient who suffers from dyspnea and eventually choking. Ankylosis and no mobility of the arythenoids, secondary to chronic inflammatory process in the cricoarythenoid joint, induce in the chronic phase bilateral vocal cord paralysis with symptoms such as stridor, horseness, dyspnea and also pain during speaking and swallowing in the acute phase. The treatment for cricoarythenoid arthritis with bilateral vocal cord paralysis include operations for improvement of breathing and voice. Tracheostomy gives an immediate solution for acute medical condition of dyspnea, resulting from the location of the vocal cords in paramedian or median position, due to their immobility. There are other operations aiming to produce adduction of the vocal cords and widen the glottic inlet and thereby improve the airway condition. The family physician needs to consider the damage and fixation of the vocal cord in patients with advanced arthritis. Patients who have rheumatic arthritis need an otolaryngologic follow up and periodic laryngoscopic evaluation in order to prevent delayed diagnosis of bilateral vocal cord paralysis which endangers the patient's airway. It is recommended to be examined by an otolaryngologist and also to evaluate the vocal cords as part of the pre-operative evaluation of the anesthesiologist, as performed in the evaluation of the larynx in patients prior to thyroidectomy. This is a case study of a patient who had severe rheumatoid arthritis and developed cricoarythenoid arthritis and bilateral vocal cord paralysis presented with stridor and dyspnea and needed an immediate tracheostomy. Cricoarythenoid arthritis with bilateral vocal cord paralysis including treatments options are discussed. PMID- 17352275 TI - [Eating and swallowing disorders in children]. AB - INTRODUCTION: Eating and swallowing disorders in children are common and reflected in several symptoms, yet they are not well known. PATIENTS: Three patients are presented to demonstrate the spectrum of the problems, the diagnosis and the multidisciplinary team approach to treatment. DISCUSSION: To enable safe eating and thriving, swallowing and eating disorders need to be recognized and treated, according to the child's development. This can be done by a multidisciplinary team, such as the one at The Edith Wolfson Medical Center. PMID- 17352276 TI - [Associated brachial cleft anomalies in the cat eye syndrome]. AB - The cat eye syndrome is a congenital malformation usually associated with anal atresia, ocular coloboma, downward slanting eyes, microphthalmia, hypertelorism, strabismus, preauricular tags or fistulas, congenital heart defect particularly septal defect, urinary tract abnormalities, skeletal anomalies and frequently mental and physical retardation. A small supernumerary chromosome (smaller than chromosome 21) is present, frequently has 2 centromeres, is bisatellited and represents an inv dup 22 (q11). A two years old female presented to our department with an association of cat eye syndrome with preauricular tags and a first branchial arch anomaly. This article discusses the surgical management and the association between the cat eye syndrome and first branchial cleft anomaly. PMID- 17352277 TI - [Cochlear implantation in children]. AB - The pediatric cochlear implant program was launched in our department in 1990. A year earlier, we began the cochlear implant program in our center. Cochlear implant surgery changed the life of implanted children by enabling integration into the regular education program. The experience of the Sheba Medical Center is presented in 286 children who were operated on between the years 1990-2005. Hearing results were examined using questionnaires and designated audiology tests. Improvement in the hearing ability of implanted children was noted, especially in those who underwent implantations in their first years of life and in those who had previous experience using hearing aids. Post-operative complications were scanty and similar to those reported in the literature. The incidence of device failure is decreasing over the years due to production improvement. The frequency of electronic failure was found to be similar to those described in the literature. PMID- 17352278 TI - [Cochlear implantation in children with otitis media: third stage of a long-term prospective study]. AB - INTRODUCTION: The age at which cochlear implantation (CI) is performed in children generally corresponds to the age at which the prevalence of otitis media (OM) is highest. The risks of problematic middle ear infection and of potential spread of middle ear infection along the electrode array into the cochlea and the central nervous system are relatively high. Thus, it is necessary to establish a practicable protocol aimed at controlling OM prior to and after CI in young candidates. OBJECTIVE: To assess the risk for otitis media after cochlear implantation in otitis media (OM)-prone and non-OM-prone children who were treated according to a structured protocol designed to control OM prior to implantation. PATIENTS AND METHODS: Of 113 children referred for cochlear implantation during the study period, and were implanted under the age of 7 years, 70 were classified as OM-prone (Group A) and 43 as non-OM-prone (group B). Group A patients were managed according to a structured protocol aimed at pre implantation control of OM. Postimplantation follow-up ranged from 6 to 75 months (average 35.5 months). RESULTS: In the OM-prone group of children, the mean age at referral and at implantation was significantly lower and the mean interval between referral and implantation significantly higher than in the healthy group. During the first month after implantation 18 children suffered from acute otitis media, the vast majority of them (16) belonged to the OM-prone children (22.8% of this group) and 2 subjects belonged to the non-OM-prone children (4.6% of this group). During the late post-operative period 28 of the OM-prone children (40%) and 4 of the non-OM-prone children (9.3%) developed acute OM in the implanted ear. Eleven (9.7 %) of these cases, (10 belonging to the OM-prone group B (14%), and one belonging to the non-OM-prone group A (2.3%)) proved to be recurrent and therapeutically challenging. Three subjects developed acute mastoiditis without intracranial complications. Each episode of mastoiditis or otitis media was controlled conservatively without any need of surgical drainage of the mastoid. This group of challenging cases did not differ from the OM-prone children who did not prove to be OM-challenging post-CI in regards to age at referral, age at CI and average number of ventilation tube (VT) operations prior to CI. Most pathogen isolations (65%) from OM or from VT drainage developed after CI were typical pathogens for acute otitis media (AOM). However, the percentage of non-typical AOM pathogen isolation increased with time after CI. CONCLUSIONS: Early referral led to early implantation, even in children susceptible to OM. The incidence of OM decreased after implantation in both groups, but was still significantly higher in the OM-prone group. Meanwhile, prior to CI it is not possible to predict the cases that become therapeutically challenging at a later stage. PMID- 17352279 TI - [Recurrent pleomorphic adenoma of the parotid gland]. AB - Recurrent pleomorphic adenoma of the parotid gland is a challenging surgical experience. Resection of such recurrences is associated with an increased risk of facial nerve injury and a higher incidence of recurrent disease. Resection of the primary tumor with a cuff of normal tissue around it during the primary surgical resection lowers the incidence of such metastases, but even with them, metastases still occur. Surgery of such metastases requires high surgical expertise as well as intra-operative decision-making. Intraoperative monitoring of the facial nerve may be of help during these surgical interventions, but the surgeon need not rely on the monitor only, but identify the nerve based on its well known anatomy and use the monitor as another surgical tool for safe removal of the tumor. Resection of the facial nerve or some of its branches is usually not necessary, but if the nerve is the only site making the resection an incomplete one - then the nerve should sometimes be resected, after sufficient effort has been made to preserve it. In these cases, the nerve should be reconstructed with a cable graft (mainly greater auricular or sural) when possible. Radiotherapy is reserved for patients that had multiple recurrences or had massive tumor spillage during their surgical procedure of the recurrent tumor. PMID- 17352280 TI - [Return to work with heart disease]. AB - Cardiovascular disease is the leading cause of death in developed countries (40% of all causes of mortality). Heart disease is common in the working age population and thus it contributes to a decline in employees' fitness for work. In Israel about 80% of patients recuperating from myocardial infarction (MI) return to work. However, long term employment may be as low as 50% and its patterns are associated predominantly with patient age and job characteristics, as compared to measures of illness severity or the method of coronary revascularization. The need for clinical guidelines in the management of return to work after myocardial infarction has recently led to the initiation of a joint committee of the Israeli National Heart and Occupational Societies. These clinical guidelines have been published and are summarized in this issue. For most common cardiac disease, including heart failure, valve disease and angina, patients can exert themselves up to onset of symptoms. Therefore, patients with functional capacity I and II, as estimated by New York Heart Association (NYHA) criteria, can return to their previous work. Timing of return to work for patients with asymptomatic uncomplicated cardiac disease: Post MI within 4 weeks, CABG within 4-8 weeks and percutaneous interventions within 1 week. For patients with a strenuous job or in NYHA functional capacity III or IV, a few weeks of delay and exercise or other functional testing may be needed. There are a few exceptions including patients with strenuous work or specific cardiac diseases as hypertrophic cardiomyopathy, severe aortic stenosis and Marfan's syndrome. In such cases, cardiological and occupational specialist advice should be sought. PMID- 17352281 TI - [Work related musculoskeletal disorders of the upper extremity]. AB - Various musculoskeletal syndromes are considered to be work-related. The prevalence of a few of these syndromes is high. Repeated or continuous application of force over a prolonged period to the same muscle group, tendon, bursa or peripheral nerve, can cause cumulative damage. Non-physiological position of the upper limb during work time, can add further injury. The most frequent syndromes are tendonitis and tenosynovitis, nerve entrapment neuropathies and muscle injuries. Frank arthritis is relatively rare. Early diagnosis is usually associated with better prognosis and full recovery within few months. PMID- 17352282 TI - [Gynecomastia as a complication of hormonotherapy for prostate cancer: effect of prophylactic breast irradiation]. AB - Gynecomastia is a benign condition characterized by proliferation of mammary glandular tissue. Hormonotherapy with bicalutamide for prostate cancer is one of the causes of gynecomastia. The well known aim of treatment is to decrease psychological distress and to improve cosmetic appearance. Prophylactic breast irradiation may prevent the appearance of gynecomastia. PMID- 17352283 TI - [Current management of idiopathic clubfoot]. AB - Idiopathic clubfoot, one of the most common problems in pediatric orthopaedics, is characterized by a complex three-dimensional deformity of the foot. The treatment of clubfoot is controversial and continues to be so. Since nonsurgical management was thought not to yield adequate correction and a durable result, most children with idiopathic clubfoot have undergone surgery with extensive posteromedial and lateral release. However, surgical management caused residual deformity, stiffness, and pain in some children. Therefore, the favorable long term results with the Ponseti and French methods of nonsurgical management have garnered interest. Today extensive surgical treatment is no longer necessary in more then 90% of congenital clubfeet. This review aims to assess the different methods of clubfoot treatment used over the years in light of an evolving understanding of the pathoanatomy of the deformity and also clarify factors that allow a safe, logical approach to clubfoot management. PMID- 17352284 TI - [What's new in postmenopausal osteoporosis]. AB - The ability of bone to resist fracture is the best indicator of bone quality and is potentially related to several bone properties, including quality, turnover rate, microarchitecture, geometry, and mineralization. The U.S. Preventive Services Task Force recommends routine osteoporosis screening (by DXA) beginning at age 65 years for all women, and beginning at age 60 years for those at high risk. These recommendations are controversial, because no randomized trial results have shown that screening ultimately prevents fractures. Additional radiologic procedures may be helpful, particularly to define bone fractures. Several serum and urine biochemical tests are now available that provide an index of the overall rate of bone turnover and are usually characterized as those related primarily to bone formation or bone resorption. The results of clinical trials have shown that antiresorptive agents reduce fracture risk to varying degrees and that the magnitude of the reduction in fracture risk is proportional to the magnitude of changes in bone turnover and bone mineral density (BMD). The bisphosphonates are currently the preferred agents for the prevention and treatment of osteoporosis with the goal of reducing the risk of both vertebral and nonvertebral fractures. They are retained over time in the skeleton and may exert long-term effects. A 10-year course is safe and effective in women with high risk for fractures. A temporary stop may be considered after 5 years of treatment in less severe cases, on an individual basis. Calcitonin and raloxifene have no significant effect on the risk of hip and other nonvertebral fractures. Teriparatide, a synthetic 1-34 parathormone stimulates new bone formation, repairing architectural defects and reducing the risk of vertebral and all nonvertebral (but not hip) fractures in severe postmenopausal osteoporosis. Its administration is limited by time (no more than 2 years) and cost. The effect of vitamin D and calcium on the fracture's risk is controversial and its administration as the sole treatment is recommended mainly for elderly and other populations with Vitamin D deficiency. It is mandatory to supply the recommended vitamin D and calcium to the whole population independent of the need for therapy. Strontium ranelate appears to stimulate bone formation and reduce resorption and has been shown to reduce moderately vertebral and non-vertebral fractures in postmenopausal women with established osteoporosis. New medications are in development, including antiresorptive and bone formation stimulating agents. PMID- 17352285 TI - [Role of natural killer cells in normal pregnancy and recurrent pregnancy loss]. AB - Pregnancy is an immunological mystery. The conceptus survives and develops despite being an allogenic transplant, in terms of classical immunology. Natural killer cells are the predominant immune-cell population in the early human placenta. The role of these cells in human pregnancy is not fully established, yet it presumed they are required for placental development and local immunomodulation at the maternal-fetal interface. The purpose of this review is to examine recent progress in characterizing natural killer cells, the quantitative and qualitative changes that occur in these cells through pregnancy. We will also point out the possible role of these cells in the maintenance of normal pregnancy and the pathogenesis of recurrent pregnancy loss. PMID- 17352286 TI - [G-spot and female ejaculation: fiction or reality?]. AB - The G-spot is an ill-defined region, located on the anterior vaginal wall, in its upper outer third, suggested by Ernst Grafenberg, and commemorates the first letter of his name. This area is sensitive to tactile touch, which, when applied, is claimed to result in an intense female orgasm. The G-spot is thought to be the vaginal part that lies beneath the posterior part of the "female prostatic gland", which, when stimulated, results in female ejaculation during orgasm. G spot and female ejaculation have been studied intensively during the last 50 years and there is scientific (anatomical and biochemical) evidence for their existence. However, this evidence has been challenged, and the debate regarding the existence of the G-spot and female ejaculation as true clinical entities is still ongoing. PMID- 17352288 TI - [Birth by desire]. PMID- 17352287 TI - [Joseph Carey Merrick the man in the flannel mask]. AB - Joseph Carey Merrick was born like all other children in his time, yet his life story was unlike those of other people due to an odd disfiguring disease that devastated his appearance. Despite his personal and social handicap caused by his deformity, Joseph Merrick did his best to survive the challenges of every-day living in a hostile and unsympathetic world. This is the story of a man who had to cover his face from the crows behind a mask, a man whose bones have yet to find eternal peace. This is the story of the "elephant man". PMID- 17352289 TI - [Specific features of early embryogenesis in apomictic Poa pratensis L]. AB - We studied the early stages of embryo formation in apomictic Poa partensis L. It was shown that during transition to parthenogenesis, at least at the initial stages of embryogenesis, the algorithm of development of the sexual embryo is preserved. This could be due to the system of genetic control of embryogenesis, common for amphimixis and apomixis. We described asynchrony of developmental processes both within the efflorescence (asynchronous maturation of ovules) and within the ovule and even gametophyte (different timing of induction of apoarchesporic initials and oospores). This feature of pseudogamous apomicts allows them to produce simultaneously both sexual and apomictic progenies. PMID- 17352290 TI - [Daily temperature gradients and processes of organogenesis in apical meristem of Cucumis sativus L]. AB - We studied the influence of daily temperature gradients on organogenesis in apical and axil shoot meristems at different developmental stages in Cucumis sativus L. The level of organogenic activity of meristems was determined according to the number of leaf primordia on the main and lateral shoots, number of 2nd order shoots, and rudiments of flowers of different levels of development. At the studied ontogenetic stages (mesotrophic seedling or juvenile state), plants were grown under the controlled conditions: photoperiod 12 h, light intensity 100 Wt/m2, range of mean daily temperatures 20 ... 30 degrees C, and daily temperature gradients -20 ... +20 degrees C. After the temperature treatment, some plants were returned to the optimal, for growth and development, conditions for two weeks (aftereffect). Three types of organogenic activity of meristems in response to the influence of variable daily temperatures were described: stimulation, inhibition, or absence of effect. The phenomenon of stimulation includes two subtypes: optimization, when a maximum effect, observed at other constant temperatures, was attained under the influence of variable temperatures and maximization, when maximum values markedly exceeded those at constant temperatures. The patterns described are preserved on the whole in the aftereffect of daily temperatures. PMID- 17352291 TI - [Transgene 6A-99 is a molecular marker of developing somatosensory cortex in mice]. AB - Among dozens of known genes, active in the developing cortex, none possessed expression strictly limited by one functional area of the cortex. We found that in 6A-99 transgenic mice, Lac-Z-reported gene was expressed selectively in the somatosensory cortex. In the primary somatosensory cortex, expression was localized in the barrel field, including the zone of representation of vibrissae, fore and hind limbs, jaws, and head. In addition, LacZ-expressing cells were found in the secondary somatosensory cortex, as well as in the nuclei of hypothalamus and dorsal and caudal raphe nuclei. In the cortex, expression of transgene 6A-99 began on day 3 of postnatal development (P3) and embraced only the area of primary somatosensory cortex: zones of representation of the snout, vibrissae, and lower jaw. On P5, pronounced expression 6A-99 was detected in the secondary somatosensory cortex and zone of representation of fore paws. Expression in the zone of representation of hind paws was observed on P7. Expression of 6A-99 in the somatosensory cortex disappeared by P50, the age of final functional maturation of the cerebral cortex. Our results suggest that the regulation of transcription in the developing mouse somatosensory cortex differs from those in other cortical areas. Transgene 6A-99 may serve as a specific molecular marker of the developing somatosensory cortex in mice and can be used for studying the mechanisms underlying genetic and epigenetic control of the neocortex functional regionalization. PMID- 17352292 TI - [Haploadaptivity of tumor suppressor lgl and ontogenesis in Drosophila melanogaster: increased survival rate and life span under stress conditions]. AB - Mutations of tumor suppressor lgl induce neuroblastoma and malignant transformation of epithelial larval tissues in Drosophila. We have already shown that heterozygotes for lethal null variants lgl/+ are widespread in natural populations. In order to elucidate this paradox, we analyzed the parameters of biological adaptation of the carriers of one dose of the tumor suppressor. We studied the patterns of embryonic survival rate of lgl/+ flies under the conditions of competition for life resources and development at elevated and lowered temperatures (29 and 16 degrees C), influence of stress thermal conditions on life span, influence of short-term temperature stress during prezygotic period in the course of oogenesis of mothers on survival rate of F1 progenies, and resistance of heterozygotes for different lethal lgl alleles against RNA virus DCV. The loss of one dose of tumor suppressor lgl+ provided for increased survival rate and life span of lgl/+ heterozygotes under stress conditions. This phenomenon was called haploadaptivity. Important features of adaptogenesis were established in lgl/+ heterozygotes: dependence on the maternal genotype and critical periods in development. The increased survival rate of F1 progenies was determined already during early oogenesis of their lgl/+ mothers at the proembryo stage. With respect to humans, this conclusion draws attention to the oogenesis-dependent transgeneration aspect of determination and expression of mutant factors of risk, including tumor suppressors. The data obtained are essential for understanding of the causes of spreading null variants for the genes related to multiple pathologies, including cancer, in human populations. PMID- 17352293 TI - [Specific features of expression of aspartate aminotransferase genes in early development of some cyprinid fishes and their intergeneric F1 hybrids]. AB - Temporal parameters of expression of the aspartate aminotransferase gene Aat-1 parental alleles were studied in early development of intergeneric reciprocal F1 hybrids of the bream, roach, and blue bream. When the first AaT-1 expression was timed to the early stages (late blastula-gastrula), the gene parental alleles were activated asynchronously according to the maternal types (blue bream x roach hybrids). When the first Aat-1 expression was timed to later stages (yolk sac resorption), the parental alleles were activated synchronously (bream x roach, roach x bream, and roach x blue bream hybrids). The pattern of activation of embryonic genes is determined by the maternal environment and the influence of allele interactions is not excluded: Aat-f/Aat-sl (bream x roach, roach x bream, and roach x blue bream) and Aat-sl/Aat-med (blue bream x roach). PMID- 17352294 TI - [Biogenic amines regulate the reproductive function in Drosophila as neurohormones]. AB - We studied the influence of experimental increase in the octopamine and dopamine content on the level of juvenile hormone degradation, oogenesis, and fertility in wild type D. virilis flies. Feeding of flies on octopamine led to a significantly decreased level of juvenile hormone degradation (increased titer) in young and sexually mature females, rather than in males, markedly decreased the number of vitellogenic (stages 8-10) and mature (stage 14) oocytes), and sharply reduced fertility. Feeding of flies on dopamine decreased the juvenile hormone degradation (increased titer) in young wild type females and increased it (lowered the juvenile hormone titer) in sexually mature females, as well as decreased the fertility of wild type females to a level characteristic for D. virilis line with a mutation doubling the endogenous dopamine level. A possible mechanism of the influence of these amines on the reproductive function in Drosophila as neurohormones is discussed and a conclusion is drawn that the reduced fertility of females at an increased level of amines appears to be related to an increased level of ecdysteroids, which is caused by an increased, as a result of decreased degradation, juvenile hormone titer. PMID- 17352295 TI - [Postnatal development of corticosteroid function of the adrenals in C57BL/6J-Ay mice]. AB - We studied postnatal development of corticosteroid function of the adrenals in mice during the period of elevated activity of the hypothalamic-pituitary-adrenal system and the influence of mutant gene Ay on this process. Normally, a corticosterone peak in blood and increased basal and stimulated steroidogenesis in vitro are observed in 3-week old mice. In 3-week old Ay/a mice (hyperexpression of protein agouti) a corticosterone peak in blood is lowered and genotypic differences in steroidogenesis in vitro are absent, as compared to a/A mice (absence of agouti), while at the ages of 10 and 15 weeks, there were no genotypic differences in the blood level of corticosterone and steroidogenesis in vitro was elevated. Thus, a high level of corticosterone during the period of elevated activity of the hypothalamic-pituitary-adrenal system in 3-week old mice is determined by enhanced steroidogenic function of the adrenals. Mutant gene Ay in male mice affected the postnatal development of the adrenal function: the peak of corticosterone in blood was lowered during the period of elevated activity of the system. PMID- 17352296 TI - [Management recommendations in patients with methotrexate intoxication]. AB - Intoxication due to insufficient renal clearance developed in 2 patients, a 54 year-old man and a 61-year-old woman, who were under treatment with methotrexate (MTX) for a primary cerebral lymphoma and a recurrence of large-cell B-cell-non Hodgkin lymphoma, respectively. Both were treated with folinic acid rescue, thymidine, and alkalisation of the urine. MTX is a cytotoxic drug that is often used in oncology and rheumatology. Significant and even lethal toxicity can develop when the elimination ofMTX is delayed or when supportive care, such as folinic acid rescue, is inadequate. Delayed elimination can be caused by reduced renal function, by the 'third space' phenomenon such as in case of ascites, pleural fluid accumulation and oedema, and by drug-drug interactions leading to reduced renal function or a disturbance in the plasma protein binding ofMTX. Once toxicity has developed, the therapy must be directed at protection of the normal tissues, restoration of renal function and hence the renal elimination ofMTX, restoration of the alkalisation of the urine, and general supportive therapy. PMID- 17352297 TI - [Perioperative use of psychotropic drugs; advice based on casuistic and 'expert based medicine']. AB - Little scientific evidence is available on the continuation of psychotropic drugs in the perioperative period. Clinicians often have to rely on case reports and small case series. However, case reports of rare events, such as life-threatening interactions between psychotropic drugs and anaesthetics, do not provide reliable data on the frequency of such events and may lead to a rather defensive approach. Recommendations were published recently based on expert opinion from a multidisciplinary group. This proposal could be used for the development of an official, evidence-based guideline on the perioperative use of psychotropic drugs. The quality of such a guideline would be improved by prospective cohort studies that compare events in patients who discontinue psychotropic medication with those in patients who continue medication for fear of severe withdrawal symptoms. PMID- 17352298 TI - [Angiography and embolisation to control bleeding after blunt injury to the abdomen or pelvis]. AB - Angiography and embolisation are being increasingly used to control bleeding following abdominal and pelvic trauma. CT is a useful tool to select patients for such intervention-radiological angiography. The application ofangiography and embolisation requires a specific local infrastructure, logistics and expertise on the part of the radiologist, traumatologist and anaesthetist. The main indications for angiography and embolisation are: contrast blush on the CT scan and clinical signs of ongoing bleeding; they are also indicated as an adjunct to damage control procedures. Angiography and embolisation are successful in about 90% of the patients; complications occur in < 10% of the patients. An accurate estimate of the patient's physical condition, a correct assessment of the severity of the injury, and a multidisciplinary approach are important factors in the success of embolisation therapy. PMID- 17352299 TI - [Measures for patients taking psychotropic drugs who undergo elective surgery]. AB - Psychotropic drugs can increase the risk of perioperative complications when given in combination with anaesthesia. Evidence-based guidelines that address this issue are lacking. Consensus-based recommendations were formed for the perioperative management of these patients based on the available literature and a systematic evaluation of perioperative risks by the medical specialists directly involved. Patients who use lithium, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants or clozapine are at risk of experiencing adverse interactions. The anaesthesiology literature recommends discontinuing irreversible MAOIs and lithium in all cases, and tricyclic antidepressants in patients with systemic disorders. With the exception of lithium, the risks of psychiatric relapse or recurrence associated with discontinuation necessitate intensive integrated psychiatric treatment. Continuation of treatment under strict haemodynamic observation may also be an option in some cases. Patients taking selective serotonin reuptake inhibitors (SSRIs) should be observed carefully for psychological instability and physical abnormalities, and clinicians should be aware of medications that could increase the risk of haemorrhage when used in combination with SSRIs. In these cases, a psychiatrist should be consulted. The same is true for patients taking antipsychotic or other antidepressant medication who develop psychological instability or have a systemic disorder. Given the widespread use ofpsychotropic drugs and the seriousness of the associated risks, it is recommended that the decision whether to continue or discontinue psychotropic medication should become a standard component of preoperative assessment. PMID- 17352300 TI - [Diagnostic image (310). A man with a knife in his head]. AB - A 30-year-old man presented with a knife in his head; it had perforated the left temporal area and its point was located in the mouth. After surgical removal of the knife, the patient left the hospital without functional deficits. PMID- 17352301 TI - [Transcutaneous bilirubinometry useful in the determination of hyperbilirubinaemia in icteric neonates]. AB - OBJECTIVE: To evaluate the usefulness of transcutaneous bilirubinometry in determining the need for phototherapy in neonates with hyperbilirubinaemia and to assess whether this technique may be used as an alternative to blood tests. DESIGN: Prospective, descriptive. METHOD: Serum bilirubin and both midfrontal and midsternal transcutaneous bilirubin were measured in icteric neonates admitted to the neonatal ward of the Kennemer Gasthuis, Haarlem, The Netherlands, between 1 March and 31 December 2005. The Minolta JM-103 jaundice meter was used for transcutaneous assessment. Data were interpreted with the aid ofa scatter plot, a 2-by-2 table and receiver operating characteristics (ROC) curve. RESULTS: A total of 70 matched transcutaneous-serum bilirubin measurements were taken from 50 patients, 22 girls and 28 boys. The mean gestational age was 66 hours (range: 12 164) and the mean birth weight was 2766 grams (range: 1680-4600). The mean duration of maternal amenorrhoea was 36.2 weeks (range: 32-41.3). The coefficient of correlation between serum bilirubin and mean transcutaneous midfrontal and midsternal bilirubin was o.88 and 0.91, respectively. The negative predictive value of mean transcutaneous midfrontal and midsternal bilirubin measurement was 0.91 and 0.87, respectively, indicating that phototherapy would be correctly avoided in 91 and 87% of children, respectively. Based on the area under the ROC curve, the transcutaneous midfrontal bilirubin measurement was more reliable than the midsternal measurement. CONCLUSION: Transcutaneous bilirubin measurement was useful in determining the need for phototherapy in neonates with hyperbilirubinaemia. Use of this non-invasive screening method may help to avoid unnecessary blood sampling in neonates. PMID- 17352302 TI - [A drooping face; the importance of family history in children with recurrent peripheral facial palsy]. AB - An 18-year-old girl had experienced drooping at the left corner of the mouth for several weeks and could not close her left eye. These symptoms improved gradually and spontaneously. She had had a similar experience 2 years earlier; at that time, the right side of the face was affected. Family members reported similar episodes. After excluding Lyme borreliosis and cerebellopontine angle tumour, a diagnosis of idiopathic familial peripheral facial palsy was made. Peripheral facial nerve palsy is commonly seen in children and young adults. Obtaining a family history is helpful in these patients: a positive family history is found in 2.4-28.6% of the cases. In the absence of other symptoms, a diagnosis of idiopathic familial peripheral facial palsy should be considered. The prognosis of these patients is generally good and therapy is usually unnecessary. PMID- 17352303 TI - [Drug-induced systemic lupus erythematosus: reports to The Netherlands Pharmacovigilance Centre Lareb]. AB - Drug-induced SLE and idiopathic SLE differ in a number of important aspects, for example the male/female ratio and the age of the patients. There are also differences in incidence in different populations. The mechanism of drug-induced SLE is still largely unknown. It is generally assumed to be an allergic reaction to the drug. The database of the Netherlands Pharmacovigilance Centre Lareb contains 31 reports of SLE in relation to the use of 24 different drugs. In 3 of these cases, there was aggravation of pre-existent SLE. Infliximab and terbinafine are the most frequently reported in association with drug-induced SLE. Furthermore, the database contains a small number of reports of SLE associated with the use of antibiotics. It is difficult to determine whether all of the reported cases involve true drug-induced SLE, but a number of factors suggest that this is often the case, such as the presence or absence of skin involvement and the number of patients that recover after withdrawal of the drug. During the diagnosis of SLE, healthcare professionals should be aware of the use of drugs that might be associated with the induction of SLE. PMID- 17352304 TI - [A multicentre randomised clinical trial to evaluate the benefit of testing for thrombophilia following a first venous thromboembolism: the NOSTRADAMUS study]. AB - It is unknown whether testing patients for thrombophilia after a first episode of venous thromboembolism (VTE) and prolonging anticoagulant treatment in those with thrombophilia is justified. The NOSTRADAMUS trial, a multicentre randomised controlled trial, is being conducted to assess whether this strategy is beneficial in terms of clinical outcomes, quality of life and costs. Patients with a first VTE will be randomly assigned to one of two groups. The first group will be tested for thrombophilia and subsequently receive the test results; those in the second group will be tested but the results will not be disclosed. A total of 1336 patients will be included. Additional anticoagulant treatment for a predefined period will be initiated in patients found to have thrombophilia, while others will receive a standard predefined duration oftreatment. Primary outcomes are the risk of recurrent VTE, clinically important bleeding and the composite outcome of both. Other outcomes include overall quality of life and costs associated with outcome measures 18 months after the initial episode of VTE. PMID- 17352305 TI - [Sex, gender and health: developments in scientific research]. AB - The feminist movement was involved from its start in the struggle for better healthcare for women. The academic discipline 'Women's studies medical sciences', which developed in the 1980's, supported this struggle. Initial points given special attention in this new discipline were the autonomy of the (female) patient, the importance of the psychosocial context of symptoms and the demedicalisation of women's complaints. The focus of research has now shifted from reproductive health to female health during the entire lifespan. Furthermore, research has developed from female health to gender in relation to health, explicitly including men's health and the social constructions of masculinity. The psychosocial context ofgender-related complaints is of importance. Next, the concept 'gender' was replaced by the concept of'diversity', thus facilitating criticism of the ongoing medical concepts of neutrality and universality. In the future, research should be interdisciplinary, with explicit attention for the differences between men and women and the psychosocial context. PMID- 17352306 TI - [Symptomatic gallstone disease: an indication for surgery]. PMID- 17352307 TI - [Symptomatic gallstone disease: an indication for surgery]. PMID- 17352308 TI - Childhood ITP: when to treat? PMID- 17352309 TI - A comparative study of initial use of intravenous immunoglobulin and prednisolone treatments in childhood idiopathic thrombocytopenic purpur. AB - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is an acquired disorder characterized by immune-mediated platelet destruction. The aims of this study were to compare initial platelet count elevation and to determine the chance of developing persistent profound thrombocytopenia by intravenous immunoglobulin (IVIG) or prednisolone in the treatment of children with ITP. METHODS: Eighty seven children, aged from 3 months to 14 years old, diagnosed with ITP and initial platelet count less than 20 x 10(3)/mm3 were divided into two groups. Fifty-four patients received IVIG (1 g/kg/dose) for two days. Then, they received prednisolone treatment at a dose of 1 mg/kg/d starting on day 8 to maintain platelet count, followed by a tapering dose until day 60. Thirty-three patients received prednisolone (2 mg/kg/day) for 14-21 days, followed by a tapering dose until day 60. Platelet counts were evaluated on presentation days 2, 3, 5, 7, 30, 60, 90, 120, 150 and 180. RESULTS: Forty-four of 54 patients (81.5%) treated with IVIG demonstrated a rapid increase in platelet count above 20 x 10(3)/mm3 on the second day, compared to 13 of 33 patients (39.4%) in the group treated with prednisolone initially (p<0.01). There were no significant differences in mean platelet counts between both groups on days 3, 5, 7 or 30, 60, 90, 120, and 180 (all p>0.05). No serious bleeding, such as ICH, was noted in either treatment group. Persistent platelet counts lower than 20 x 10(3)/mm3 after 6 months of follow-up developed in 18 patients (33.3%) in the IVIG group and in 10 patients (30.3%) in the prednisolone group (p=0.480). CONCLUSIONS: In our study, patients treated with IVIG demonstrated a higher percentage of patients with platelet count increasing above 20 x 10(3)/mm3 on the second day compared with patients treated with prednisolone initially (p<0.01). However, there was no difference in developing persistent platelet counts lower than 20 x 10(3)/mm3 at 6 months of follow-up between the IVIG and prednisolone groups (p=0.480). PMID- 17352310 TI - The clinical differences between early-and late-onset pulmonary hemorrhage in systemic lupus erythematosus patients. AB - BACKGROUND: Pulmonary hemorrhage (PH) is a rare but possible fatal complication of systemic lupus erythematous (SLE). We try to better understand the clinical symptoms and prognosis in patients with SLE and PH. Furthermore, we want to know whether there is different between early-onset and late-onset pulmonary hemorrhage in SLE patients. METHODS: A retrospective review was carried out for all medical admissions of 3128 patients with the diagnosis of SLE at Chang Gung Medical Center from 1994 to 2003. Twenty SLE patients with PH were carefully reviewed. For all study subjects, the patient demographics, clinical, laboratory, therapeutic, and outcome data were collected and chest radiographs were reviewed. Seven of 20 patients with PH occurred earlier as one of the initial manifestations of SLE were subgrouped to early-onset group. The remaining 13 patients with PH were classified as late-onset group. RESULTS: During the 10-year period, there were 20 patients (16 females and 4 males) who had suffered from PH. The age distribution was between 13.2 and 55 years, (median age 25.5 years). The most predominant symptoms and signs were hemoptysis, tachypnea, and dyspnea. The patients, initially with low hemoglobin concentration, were prone to death. (mortality group vs survival group was 5.6 +/- 1.4 vs 7.9 +/- 2.0 gm/dL, p value = 0.004). The late-onset group had a higher rate of presenting with cough, and younger onset-age than that in the early-onset group. CONCLUSIONS: Low hemoglobin is a risk factor for mortality in SLE patients with pulmonary hemorrhage. Clinically, the late-onset group was younger than the early-onset group and had higher rate of presenting with cough. No statistical prognostic differences showed between late-onset and early-onset groups. PMID- 17352311 TI - Genetic and environmental predictors for pediatric atopic dermatitis. AB - BACKGROUND: The purpose of this study was to evaluate the influence of genetic and various environmental factors for atopic dermatitis (AD) occurring in the first 18 months of life. METHODS: We used the multistage stratified systematic sampling to recruit 2,048 mother-child pairs from the Taiwan National Birth Registry in 2003. Information on family history of atopy and environmental risk factors for AD of children were gathered by questionnaires at 18 months of age. Multiple logistic regressions were performed to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for risk factors of the AD after adjusting for potential confounders. RESULTS: AD was noted in 147/1618 (9.08%) of the children. We found maternal history of AD, maternal grandparents' history of AD, higher family income, and higher maternal education level increased the risk of pediatric AD. The adjusted ORs and their 95% CIs were 4.10 (1.27-13.25), 4.56 (1.39-15.00), 1.66 (1.00-2.77), and 1.71 (1.56-6.97), respectively. However, duration of breast feeding did not alter the risk estimates of AD. CONCLUSIONS: AD may be inherited preferentially through the maternal line. Prevention of special environmental exposures is urgently needed for children with maternal history of AD. PMID- 17352312 TI - The growth of Tibetan monks in south India--compared to the boys in Taiwan 10 years ago. AB - BACKGROUND: Studies comparing the growth of children between Tibetan and Han ethnic groups have not been reported. OBJECTIVE: To increase the understanding regarding the growth status of children and the growth difference between the Tibetan and Han ethnic groups. METHODS: Body weight, body height, and BMI of 894 Tibetan monks aged from 8-17 years old, residing in South India were collected, while growth information for boys in Taiwan was obtained from the Taiwan growth chart developed in 1997. RESULTS: In the 50th percentile, the median height difference between those boys 8 and 17 years of age was 46.8 cm, with a 5-6 cm increase each year. The median weight difference between 8- and 17-year-old groups was 33 kg, with a 0-6.5 kg increase each year. Each year, the BMIs of monks in the 5th, 50th, and 95th percentiles had 3.0-5.4%, 1.6-10%, and 3.1-8.8% increased rates, respectively. The differences of height and weight between the two groups increased between the ages of 9 and 14 years of age, but Taiwan boys and Tibetan monks had nearly the same height and weight at 17 years old. Based on the BMI-for-age curve, there were more Taiwanese boys overweight or obese than Tibetan monks. CONCLUSIONS: Even after using the data of ten years ago in Taiwan, Taiwanese boys had superior nutrition and growth status compared with Tibetan monks between the ages of eight and seventeen years, inclusive. In addition, racial differences might also play a significant factor in growth. PMID- 17352313 TI - Imaging findings in fibroepithelial polyps causing ureteropelvic junction obstruction: report of one case. AB - Fibroepithelial polyps causing ureteropelvic junction obstruction are rarely reported in the pediatric age group. We report a 9-year-old boy who had ureteropelvic junction obstruction that proved to be owing to benign fibroepithelial polyps. Intravenous pyelography showed hydronephrosis with filling defects at the left ureteropelvic junction. Operative exploration revealed several finger-like polypoid neoplasms obstructing the lumen. The involved segment was resected and a dismembered pyeloplasty was performed. Fibroepithelial polyps were diagnosed by histology. The clinical imaging findings, features and methods of surgical treatment of this rare lesion are discussed. PMID- 17352314 TI - 45,X/46,XX mosaicism in a mother and one of her discordant monozygotic twin daughters: report of one case. AB - Decreased fertility is one of the characteristics of Turner syndrome. Ovarian function in women with Turner syndrome is believed to be impaired because of an abnormal and very rapid maturation of oocytes and follicles. About 30% of mosaic Turner patients have partial ovarian function during puberty, but only 2-5% of them will ever become pregnant. We describe a woman with a mosaic form of Turner syndrome (45,X [6]/146,XX [94] karyotype from blood lymphocytes), who had a spontaneous puberty and normal fertility. After her second pregnancy, she gave birth to a set of monozygotic female twins; Twin B presented with a mild Turner syndrome phenotype and Twin A with a normal female phenotype. Karyotypic analysis performed on amniotic fluid and fetal blood samples demonstrated a normal 46,XX chromosome constitution in Twin A and a 45,X/46,XX mosaicism (27%:73% for amniotic fluid and 6%:94% for fetal blood) in Twin B. Postnatal cytogenetic investigation of blood lymphocytes showed the 45,X [7]/46,XX [93] mosaicism in Twin B. Further investigations of blood lymphocytes in both girls at the age of 4 years showed Twin A with a 46,XX karyotype and Twin B with a 45,X [4]/46,XX [96] mosaicism. The phenotype of twin A had a normal appearance, but webbing of the neck, low posterior hair line, shield chest, and mild psychomotor retardation were evident in Twin B. PMID- 17352315 TI - Neonatal startle disease with severe apnea episodes: report of one case. AB - Neonatal startle disease or stiff baby syndrome is a rare hereditary disease. It is often misdiagnosed as either neonatal seizure or cerebral palsy because of its characteristic exaggerated fits, which can be activated by external voice or touch. In fact, the exact diagnosis can be made easily according to the patient's family history and clinical examination at bedside. Glabellar tapping is a method to elicit the exaggerated responses, and the events can be relieved by forced knee-chest position. Herein, we report one case with hereditary startle disease accompanied with cyanosis and severe apneas, which could be relieved by forced knee-chest position and oral clonazepam. In conclusion, we suggest the diagnosis of the startle disease should be considered when newborns present the symptoms of neonatal seizure. Once the disease is noticed, we can pursue a simple method to confirm the diagnosis at bedside and unnecessary examination like magnetic resonance imaging can be avoided. PMID- 17352316 TI - [Trypanosomiases]. AB - Trypanosomiases are imported and rare parasitosis on the French metropolitan territory. They are re-emerging in some endemic areas, and their mode of transmission can lead to an increase of imported cases in a near future. They can be responsible for serious disease. In this paper, we describe the basic data concerning epidemiology, clinical features, diagnosis, treatment and prevention of sleeping sickness (Africa) and Chagas disease (Latin America). PMID- 17352317 TI - [Sweet's syndrome]. PMID- 17352318 TI - [Twins. What to say to the (future) parents?]. PMID- 17352319 TI - [Trends in the frequency of twin births]. AB - The proportion of twin delivery has increased by approximately 80% since the beginning of the seventies, due to the combined effects of treatments for sterility, accounting for two thirds of the increase, and delayed childbearing, accounting for one third. The twinning rate had previously experienced upward and downward fluctuations, due to the combined effects of various factors, especially the variations in age at childbearing or voluntary birth control. When the mean age at childbearing increases like over the last 30 years, the twinning rate tends to increase, since older women are more likely to have twins than younger women. On the contrary, when this age decreases like over the first 3 quarters of the 20th century, the twinning rate also tends to decrease. In France, the twinning rate reached a peak during World War I, associated in part with a temporary increase in the mean age at childbearing, as well as with a selection effect of the most fecund couples, which are also more likely to have twins. As for voluntary birth control, it tends to decrease the twinning rate as a result of that selection effect associated with fecundity, but in the opposite direction. PMID- 17352320 TI - [Management of twin pregnancy]. AB - The epidemic of multiple pregnancies continues albeit in a different form with twin pregnancies predominating. Determination of chorionicity is the key to management and regular monitoring by ultrasound is a hallmark of quality care. All multiple pregnancies should be offered first trimester screening by nuchal translucency for aneuploidy. Monochorial twins should be scanned at fortnightly intervals to allow complications such as twin-twin transfusion or IUGR to be detected and referral made to a fetal medicine centre. PMID- 17352321 TI - [Specific aspects of monochorionic pregnancies]. AB - Monochorionic pregnancies are at high risk of developing foetal and neonatal complications due to the presence of placental vascular anastomoses. These vascular anastomoses circulate on the chorionic plate and connect directly or indirectly the two foetal circulations. They may cause acute and chronic hemodynamic imbalance between the two foetuses and may cause significant morbidity, especially in the survivor at the time or nearly after the intrauterine death of its co-twin. In addition, some monochorionic pregnancies are complicated by twin-to-twin transfusion syndrome or twin-reversed-arterial perfusion sequence. The late embryo division (>8 days following the fertilization) originates in monoamniotic monochorionic pregnancy and conjoined twins and is also at risk of developing specific complications related to these conditions. Ultrasound represents the angular stone in the management of these pregnancies, firstly for the diagnosis of monochorionicity in the first trimester, and second by screening and monitoring of their specific complications. PMID- 17352322 TI - [Twin delivery]. AB - The number of twin pregnancies is still increasing. This should not be assessed only as therapeutic success but also as complex obstetrical challenges. The main difficulties encountered are dystocic presentations, dystocic labours, and cord prolapses. Specific multiple pregnancy dystocias as chin-to-chin interlocking twins and conjoined twins are very rare. Twin delivery is substantially worse when compared with singleton delivery, with increased morbidity and mortality principally involving the second twin. Labour induction is possible, and should be indicated between the 38th and 39th weeks of gestation. Caesarean section should be done easily, especially in case of prematurity or in case of breech presentation for the first twin. Excepting these cases and the usual caesarean section indications, there is no demonstrated superiority of the caesarean section delivery compared to the vaginal delivery. When needed, internal version and/or breech extraction should be done with intact membranes. Active management of the third stage is necessary, due to uterine surdistension easily leading to uterine atonia. PMID- 17352323 TI - [Tips and advice for twins' parents]. AB - The number of twins has been increasing for 20 years. The specific difficulties associated with raising twins have been well identified. As from the preparation for labor, it is essential to advise families on the help that is available to them (specialists, associations etc.) to anticipate the material and psychological difficulties families, and especially mothers, will face. These children and their families should be monitored so than they can be best advised at the various steps in providing care to and raising twins. PMID- 17352324 TI - [Adult twins]. AB - This paper explores the deep roots of closeness that twins share in their youngest age and their effect on their destiny at the adult age. Psychologists believe the bond between twins begins in utero and develops throughout the twins' lives. The four patterns of twinship described show that the twin bond is determined by the quality of parenting that twins receive in their infancy and early childhood. Common problems of adult twins bring about difficulties to adapt in a non-twin world. The nature versus nurture controversy has taken on new life focusing on inter-twin differences and the importance of parent-child interaction as fundamental to the growth and development of personality. PMID- 17352325 TI - [Patient checklist. Social assistance for twin pregnancies]. PMID- 17352326 TI - [Medical practice organization]. PMID- 17352327 TI - [Splenomegaly]. PMID- 17352328 TI - [Obesity in the adult]. PMID- 17352329 TI - [Benign hypertrophy of the prostate]. PMID- 17352330 TI - [Migraine and facial pain]. PMID- 17352331 TI - [Acute red swollen leg]. PMID- 17352332 TI - [The roots of human nature]. PMID- 17352333 TI - One-third of EDs may fail to meet 90-minute target for heart attack patients. AB - Consistent implementation of core strategies can help your ED cut as much as 30 minutes off your door-to-balloon time, according to the American College of Cardiology. Here are some steps you can start taking today: Work with emergency medical services (EMS) to establish a clear set of guidelines under which paramedics can perform an electrocardiogram in the field. Establish a protocol that enables the ED physician to activate the catheterization surgery room. Have a multidisciplined quality assurance team monitor your performance on a daily basis to ensure adherence to guidelines. PMID- 17352334 TI - System says ED patients will have zero wait times. AB - You can reduce your patient wait times to virtually zero with a lot of hard work, but you can't do it alone. It takes a combination of effective ED strategies and the cooperation of the other hospital departments. Create guidelines that cover the care the nurses can provide if the patient cannot see a physician right away. Establish a transitional unit outside of the ED but directed and managed by the ED manager. Urge the creation of and participation in a multi-discipline performance improvement team. PMID- 17352335 TI - Multivariable testing cuts door-to-doc times by 24%. AB - You can institute several process improvements in your ED in a relatively short time by testing several new ideas at once and determining those most likely to be successful. Brainstorm any and all ideas with your staff and then reduce the list to those most likely to be of benefit. Be sure to test ideas in combination as well as separately; sometimes the synergy of two ideas will make both stronger. Assign the charge nurse for each shift with the responsibility of seeing that the new ideas are carried out correctly. PMID- 17352336 TI - New evidence-based MTBI discharge form proposed. AB - Discharge forms based on proven risk factors and properly worded can help improve outcomes for patients who have suffered mild concussions. Following the literature will ensure that your forms do not omit important patient instructions. Do not use language that is too difficult for the average patient to understand. Try to stick to the sixth grade level. Make sure the patient knows what to expect in terms of potential impairments impacting daily activities. PMID- 17352337 TI - Mapping system gets patient to the right ED. AB - Utilizing a web-based system to monitor emergency services in your region can improve quality of care for patients transported to your facility by air, and it also can help minimize surge pressures if you are on divert. If you are linked to a regional system, you can advise emergency medical services on the speediest mode of transporting incoming patients. When you are on divert, the rest of the region will be alerted. Your staff will be more productive. By knowing exactly when patients will arrive, they can care for other victims when they might have been needlessly awaiting an arrival. PMID- 17352338 TI - Study: missed diagnoses have multiple causes. AB - Breakdowns in communication can be the root cause of many missed and delayed diagnoses. Here are some strategies you can use to improve communications: Be sure that your backup processes to ensure information is relayed are easily accessible. Have procedures in place that guarantee important results are communicated as quickly as possible. Your handoffs should be highly structured and systematically performed. PMID- 17352339 TI - Endovascular management of cerebral aneurysms: work in progress. PMID- 17352340 TI - Trust and reciprocity: foundational principles for human subjects imaging research. PMID- 17352341 TI - Perivascular spaces: normal and giant. AB - The purpose of this paper is to discuss both normal perivascular spaces (PVSs) and pathological giant perivascular spaces (GPVSs). The anatomy and physiology of normal PVSs, including important immunological and lymphatic roles, are described. Special attention is given to the Magnetic Resonance Imaging (MRI) findings of both normal and GPVSs. Furthermore, the clinical features and pathogenesis of GPVSs are explored, with special emphasis on the pathological implications of these lesions, and their relevance. It is important that symptomatic GPVSs not be mistaken for more devastating disease processes. When the lesions in question occur in a characteristic location along the path of a penetrating vessel, are isointense with cerebrospinal fluid on all MRI sequences, do not enhance with contrast material, are not calcified, and have normal adjacent brain parenchyma, their appearance is pathognomonic of GPVSs. The clinician should realize that an extensive differential diagnosis is superfluous and that biopsy is unnecessary in these patients. Instead, the clinical focus should be aimed at neurosurgical intervention, as dictated by the symptoms of mass effect. PMID- 17352342 TI - A comprehensive analysis of MRI research risks: in support of full disclosure. AB - Magnetic resonance imaging (MRI) procedures have been used for over 20 years. This modality is considered relatively safe and holds great promise. Yet, MRI has a number of risks. In order for MRI research to meet the Canadian standard of disclosure, the investigator must communicate and make note of all risks in their research protocols and consent forms. Those creating and reviewing research protocols and consent forms must take notice of the different circumstances under which MRI poses a risk. First, this paper will describe the current standard of disclosure in Canada for research participants. Second, the paper will provide a comprehensive synthesis of the known physical and psychological risks associated with MRI. Third, the paper will provide recommendations concerning areas for further investigation and risk reduction strategies. This information will thus equip researchers and research ethics boards (REBs) with the criteria needed for the composition of research protocols that meet the Canadian disclosure standard. PMID- 17352343 TI - Canadian Association of Neurosciences Review: the role of dopamine receptor function in neurodegenerative diseases. AB - Dopamine (DA) receptors, which are heavily expressed in the caudate/putamen of the brain, represent the molecular target of several drugs used in the treatment of various neurological disorders, such as Parkinson's disease. Although most of the drugs are very effective in alleviating the symptoms associated with these conditions, their long-term utilization could lead to the development of severe side-effects. In addition to uncovering novel mediators of physiological DA receptor functions, recent research advances are suggesting a role of these receptors in toxic effects on neurons. For instance, accumulating evidence indicates that DA receptors, particularly D1 receptors, are central in the neuronal toxicity induced by elevated synaptic levels of DA. In this review, we will discuss recent findings on DA receptors as regulators of long term neuronal dysfunction and neurodegenerative processes. PMID- 17352344 TI - Felix Vicq d'Azyr: anatomy, medicine and revolution. AB - Felix Vicq d'Azyr was born in 1748 in the small town of Valognes, Normandy. He studied medicine in Paris but he was particularly impressed by the lectures given at the Jardin du Roi by the comparative anatomist Louis Daubenton and the surgeon Antoine Petit. In 1773, Vicq d'Azyr initiated a series of successful lectures on human and animal anatomy at the Paris Medical School, from which he received his medical degree in 1774. He was elected the same year at the Academy of Sciences at age 26, thanks to his outstanding contributions to comparative anatomy. Vicq d'Azyr became widely known after his successful management of a severe cattle plague that occurred in the southern part of France in 1774, an event that led to the foundation of the Royal Society of Medicine in 1778. As Permanent Secretary of this society, Vicq d'Azyr wrote several eulogies that were models of eloquence and erudition and worth him a seat at the French Academy in 1788. Vicq d'Azyr published in 1786 a remarkable anatomy and physiology treatise: a large in-folio that contained original descriptions illustrated by means of nature-sized, colored, human brain figures of a quality and exactitude never attained before. In 1789, Vicq d'Azyr was appointed physician to the Queen Marie-Antoinette and, in 1790, he presented to the Constituent Assembly a decisive plan to reform the teaching of medicine in France. Unfortunately, Vicq d'Azyr did not survive the turmoil of the French Revolution; he died at age 46 on June 20, 1794. PMID- 17352345 TI - Treatment of intracranial aneurysms with hydrogel coated expandable coils. AB - BACKGROUND: Coiling of intracranial aneurysms with platinum coils sometimes results in relatively poor angiographic results which may be is related to low packing volumes achieved. Hydrogel coated expandable coils (HydroCoil) have been shown to achieve better aneurysm volume filling which may potentially result in lower recanalization rates. Currently there is limited clinical data on their safety and efficacy in aneurysm treatment. METHODS: We analyzed data from a prospectively collected database on patients treated at the Toronto Western Hospital. The analysis included the patients' characteristics, aneurysm size, packing, procedure related complications, recanalization and clinical outcome. RESULTS: Twenty-nine aneurysms were treated with HydroCoils only or in combination with other coils. The average calculated filling of the aneurysm volume was 74-76%. On the immediate post treatment angiograms, 44% of the berry type aneurysms were completely obliterated, 33% had a residual neck and, in 20%, a residual aneurysm was seen. Follow-up imaging was available in 23 cases. On imaging follow-up (from 2 days to 11 months) one dissecting aneurysm had recanalized. There were six technical/medical complications with no clinical consequences. Two clinically significant procedural related complications occurred. CONCLUSIONS: HydroCoils can be used effectively to treat intracranial aneurysms. The volume expansion allows for much greater packing than described for bare platinum coils, which may result in better long-term results. The recanalization rate is low but the limited follow-up does not allow for any conclusion regarding the long-term outcome. The complication rate is similar to larger current series using bare platinum coils. PMID- 17352346 TI - Clinical equipoise and treatment decisions in cervical spondylotic myelopathy. AB - OBJECTIVE: The primary objective of this study is to evaluate clinician attitudes towards the treatment of cervical spondylotic myelopathy (CSM) in order to determine whether clinical equipoise exists for a segment of this patient population. The secondary objective is to examine the factors that influence treatment decisions. METHODS: Cross-sectional internet-based survey of neurologists, neurosurgeons and orthopedic surgeons. RESULTS: Between 40-60% of respondents recommended surgery for (1) patients with minimal or no symptoms, but incidentally discovered increased T2 signal within the cervical cord on MRI, (2) patients with mild symptoms and indentation of the cervical cord but without increased T2 signal and (3) those with at least moderately severe clinical findings accompanied by MRI showing effacement of the thecal sac but without indentation of the cord or increased T2 signal. The severity of the radiological abnormalities most strongly influence treatment decisions. CONCLUSIONS: We conclude that clinical equipoise does exist for certain groups of patients with CSM, suggesting that a randomized controlled trial could be performed in this population. PMID- 17352347 TI - The G2019S LRRK2 mutation is rare in Korean patients with Parkinson's disease. AB - BACKGROUND: A number of causative mutations such as alpha-synuclein, parkin, UCHL1, Pink-1, DJ-1 have been identified in Parkinson's disease (PD). They are usually found in the familial cases. One mutation of great interest is the G2019S mutation in the LRRK2 gene, which has been reported in both familial and sporadic PD. Its prevalence has been reported to vary markedly among different races. We examined the prevalence of the G2019S mutation in the Korean PD population for genetic study planning. METHODS: We conducted a genetic analysis of the G2019S mutation by standard PCR and restriction digestion method. 453 PD patients were studied, 34% of whom had an age at onset of < 50 years and 3.8% had a positive family history. RESULTS: None of the 453 study subjects carried the G2019S mutation. CONCLUSIONS: Our result confirms previous reports that the G2019S mutation is rare among PD patients in the Asian population. This result supports the notion that the prevalence of this LRRK2 mutation is population specific, and that there may be a founder effect within western populations. PMID- 17352348 TI - Axial signs and magnetic resonance imaging correlates in Parkinson's disease. AB - BACKGROUND: Age-related brain changes may contribute to axial features in Parkinson's disease (PD). OBJECTIVES: To determine if ventricular volume and white matter high signal changes (WMC) are related to motor signs in PD and controls independent of age. METHODS: Patients were rated with the Unified Parkinson's Disease Rating Scale (subscore A: tremor, rigidity, bradykinesia, and facial expression; subscore B: speech and axial impairment). Steps and time taken to walk 9.144 meters were measured. Total ventricular volume (TVV) and intracranial volume (ICV) were measured on T1-weighted MRI using manual tracing software. WMC were rated on axial T2-weighted, dual-echo or FLAIR MR images using a visual scale. RESULTS: TVV (cm3) (PD: 36.48 +/- 15.93; controls: 32.16 +/- 14.20, p = 0.21) and WMC did not differ between groups (PD: 3.7 +/- 4.2; controls: 3.2 +/- 3.1, p = 0.55). Age correlated positively with ICV-corrected TVV and WMC in PD (cTVV: r = 0.48, p = 0.003; WMC: r = 0.42, p = 0.01) and controls (cTVV: r = 0.31, p = 0.04; WMC: r = 0.44, p = 0.003). Subscore B (r = 0.42, p = 0.01) but not subscore A (r = 0.25, p = 0.14) correlated with cTVV in PD. Steps and walking time correlated with cTVV and WMC in PD; cadence correlated with cTVV and steps with WMC in controls. Age-adjustment eliminated correlations. CONCLUSION: Subscore B, but not subscore A correlated positively with ventricular volume in PD, though this association was accounted for by age. Age-related brain change super-imposed on PD may contribute to axial features. PMID- 17352349 TI - Tumor effects on cerebral white matter as characterized by diffusion tensor tractography. AB - BACKGROUND: Diffusion tensor MRI fiber tractography (DTT) is the first non invasive in vivo technique for delineating specific white matter (WM) tracts. In cerebral neoplasm, DTT can be used to illustrate the relationship of the tumor with respect to adjacent WM trajectories. METHODS: Fiber tractography was used in this study to assess tumor-induced changes in WM trajectories in three cases of cerebral neoplasm: glioblastoma multiforme, meningioma, and anaplastic astrocytoma. RESULTS: Three patterns of WM alteration were identified: 1) disruption, 2) displacement, and 3) infiltration. Tumor disruption of WM tracts was observed in glioblastoma multiforme, which terminated fibers crossing the corpus callosum. In meningioma, DTT illustrated bulk displacement of the corticospinal tract in the affected hemisphere as well as preservation of the deviated axons. In anaplastic astrocytoma, fiber tracking demonstrated disruption of WM tracts at the tumor origin as well as intact axons through areas of tumor infiltration. CONCLUSIONS: Fiber tracking results correlated with the clinical and histopathological features of the tumor. Larger case series will be required to determine if fiber tracking can add accuracy to existing imaging methods for grading tumors. PMID- 17352350 TI - ALS incidence in Nova Scotia over a 20-year-period: a prospective study. AB - OBJECTIVE: Previous studies have suggested that the incidence of amyotrophic lateral sclerosis (ALS) in Nova Scotia is relatively high and increasing over time. This study was performed to determine the current incidence of ALS in Nova Scotia and to compare this to data collected in 1984 and 1995. METHODS: All physiatrists and neurologists were surveyed on a monthly basis over one year to record all new cases of ALS diagnosed in Nova Scotia. Data was compared to that collected using similar methods in 1984 and 1995. To validate our methods, we also performed a retrospective study using a provincial health care database. RESULTS: There were 21 new ALS cases in Nova Scotia during the 2003 study period, yielding a crude incidence of 2.24/100,000. The age-adjusted incident rate for 2003 was 2.13 (95% CI = 0.11-4.15). The age-adjusted rate for 1995 was 2.3 (95% CI = 0.08-4.53) while the age-adjusted rate for 1984 was 2.22 (95% CI = 0.13 4.32). Analysis of provincial health records identified 24 cases of ALS and an age-adjusted incidence of 2.44/100,000. CONCLUSIONS: The age-adjusted incidence of ALS in Nova Scotia has remained stable over the period 1984-2003. The incidence is similar to that reported in several other parts of the world. PMID- 17352351 TI - Recurrent stroke/TIA in cryptogenic stroke patients with patent foramen ovale. AB - BACKGROUND: Patent foramen ovale (PFO) is present in 40% of patients with cryptogenic stroke and may be associated with paradoxical emboli to the brain. Therapeutic options include antiplatelet agents, anticoagulation, percutaneous device and surgical closure. We assessed the hypothesis that there are differences in rates of recurrent TIA or stroke between patients in the four treatment groups. METHODS: Patients presenting from January 1997 with cryptogenic stroke or TIA and PFO were followed prospectively until June 2003. Treatment choice was made on an individual case basis. The primary outcome was recurrent stroke. The secondary outcome was a composite of stroke, TIA, and vascular death. RESULTS: Baseline. Our cohort consisted of 121 patients; 64 (53%) were men. Median age was 43 years. Sixty-nine percent presented with stroke and 31% with TIA. One or more vascular risk factor was present in 40%. Atrial septal aneurysm (ASA) was present in 24%. Treatment consisted of antiplatelet agents (34%), anticoagulation (17%), device (39%) and surgical closure (11%). Follow-up. Recurrent events occurred in 16 patients (9 antiplatelet, 3 anticoagulation, 4 device closure); 7 were strokes, 9 were TIA. Comparing individual treatments there was a trend toward more strokes in the antiplatelet arm (p = 0.072); a significant difference was seen for the composite endpoint (p = 0.012). Comparing closure versus combined medical therapy groups, a significant difference was seen for primary (p = 0.014) and secondary (p = 0.008) outcomes, favoring closure. Age and pre-study event predicted outcome. CONCLUSION: Patent foramen ovale closure was associated with fewer recurrent events. Complications of surgical and device closure were self-limited. PMID- 17352352 TI - Uveitis associated with Primary Angiitis of the Central Nervous System. AB - BACKGROUND: In Primary Angiitis of the Central Nervous System (PACNS), disease is typically limited to the brain and spinal cord although other organs may be affected. Uveitis is occasionally seen in systemic vasculitides but is not a recognized manifestation of PACNS. We describe two patients who developed PACNS following the onset of uveitis. CASE DESCRIPTIONS: Case 1--a 47-year-old male suffered multiple TIAs and left pontine stroke shortly after two episodes of diffuse uveitis. A cerbral angiogram demonstrated multiple caliber changes within several intracranial vessels. Cyclophosphamide was added after his stroke occurred during pulse methylprednisolone therapy. Case 2--a 35-year-old male suffered a spinal cord TIA followed by hemispheric and brainstem infarctions two months after an episode of uveitis and Bell's palsy treated with oral prednisone. A cerebral angiogram demonstrated multiple caliber changes within several intracranial vessels. He was successfully treated with oral prednisone and cyclophosphamide. CONCLUSIONS: Uveitis should be considered a recognized feature of PACNS. Combination immunosuppressive therapy with prednisone and cyclophosphamide may be necessary for successful treatment. PMID- 17352353 TI - A safe and effective method for treatment of chronic subdural haematoma. AB - OBJECTIVE: Burr-hole irrigation and burr-hole drainage without irrigation are the most popular methods for treatment of chronic subdural haematoma. It is not well known if irrigation is necessary or which method has a higher recurrence rate. We compared the recurrence rates of those two methods. MATERIALS AND METHODS: Forty two patients were treated by burr-hole irrigation (irrigation group), whereas 38 patients were treated by burr-hole drainage (drainage group). Recurrence rate and its relation with sex, age, haematoma localization and aetiology were investigated in both groups. RESULTS: There was no significant difference between recurrence rates of the two groups. There was also no correlation between recurrence rate and age, sex, haematoma localization, or aetiology. CONCLUSIONS: There was no significant difference between recurrence rates of the two groups. Since the burr-hole drainage method is simpler to carry out, its use may be preferable. PMID- 17352354 TI - MRI findings in an immunocompromised boy with CNS fungal infection. PMID- 17352355 TI - A patient with leg weakness. AB - The present case was typical in many respects for neuroinvasive WNV infection. The differential diagnosis considered was appropriately comprehensive. The present case also reminds us that little or no abnormalities will be seen on imaging in many cases, and that initial serology may be negative and should be repeated beyond the acute phase ante- or postmortem. Fortunately, specific antibodies are also now available for identification of viral proteins in tissue although sensitivity of the latter may be affected by the stage of infection and sampling of areas bearing a higher viral load. West Nile Virus, along with other emerging infections, serves notice of the health care implications of humanity's globalization of ecosystems. PMID- 17352356 TI - A retrospective study of multiple sclerosis in Siriraj Hospital, Bankok, Thailand. AB - OBJECTIVE: To determine the demographic and clinical data of Thai multiple sclerosis (MS) patients. METHODS: A retrospective study of 72 patients attending the MS clinic at Siriraj Hospital, Mahidol University, Thailand between January 1997 and June 2004. RESULTS: Fifty-eight patients (81%) were classified as clinically definite MS, 5 (7%) as Devic's syndrome, and 9 (13%) as possible MS. There were 62 females (86%) and 10 males (14%). Age at onset was 33 +/- 12 years with a mean relapse rate of 1.2 +/- 1.0 attacks per annum. None had a family history of MS. Visual impairment (53%) was the most common manifestation. Only 16% had classic (western) form of MS. Positive oligoclonal bands were found in 21%, visual evoked potentials with a typical delayed latency in 28%. MRI brain lesions compatible with McDonald's criteria were seen in only 24%, and spinal MRI brain longer than 2 vertebral bodies in 62%. The mean Kurtzke's Expanded Disability Status Scale (EDSS) was 3.0. CONCLUSIONS: Thai MS patients had much more female occurrence, no family history, common optico-spinal form, long spinal MRI lesions and low positive CSF oligoclonal bands. PMID- 17352357 TI - Tako tsubo cardiomyopathy secondary to seizures. PMID- 17352358 TI - Mechanisms of action of IVIG in adult onset Rasmussen's encephalitis. PMID- 17352359 TI - Gray-blue sclerae and osteopenia secondary to osteogenesis imperfecta. PMID- 17352360 TI - Coronary aneurysm in Kawasaki disease. PMID- 17352361 TI - Safety while swimming in a sea of energy. PMID- 17352362 TI - Designing risk-adapted therapy for multiple myeloma: the Mayo perspective. PMID- 17352363 TI - Use of cellular telephones in the hospital environment. AB - OBJECTIVE: To determine whether cellular telephones used in a normal way would cause interference with medical devices located in patient care areas of hospitals. METHODS: Two cellular telephones from different cellular carriers were tested in various patient care areas between February 15, 2006, and June 29, 2006. To monitor the medical devices and equipment in the patient care areas during testing, we observed the device displays and alarms. RESULTS: Interference of any type occurred in 0 of the 75 patient care rooms during the 300 tests performed. These 300 tests involved a total of 192 medical devices. The incidence of clinically important interference was 0% (95% confidence interval, 0%-4.8%). CONCLUSIONS: Although cellular telephone use in general has been prohibited in hospitals because of concerns that these telephones would Interfere with medical devices, this study revealed that when cellular telephones are used in a normal way no noticeable interference or Interactions occurred with the medical devices. PMID- 17352364 TI - Proton pump inhibitor therapy for peptic ulcer bleeding: Cochrane collaboration meta-analysis of randomized controlled trials. AB - OBJECTIVE: To evaluate the efficacy of proton pump inhibitors (PPIs) in treating peptic ulcer bleeding. MATERIAL AND METHODS: We searched the MEDLINE, EMBASE, CENTRAL, Cochrane Library, and metaRegister of Controlled Trials databases and published proceedings of major meetings through November 2004 for randomized controlled trials that compared oral or intravenous PPIs with placebo or a histamine2-receptor antagonist for peptic ulcer bleeding. Pharmaceutical companies and relevant experts were contacted. Data extraction and assessment of study validity were performed independently in duplicate. Assessed outcomes were 30-day all-cause mortality, rebleeding, surgery, and repeated endoscopic treatment. Influence of study characteristics on outcomes was examined by subgroup analyses and meta-regression. RESULTS: We included 24 trials (4373 participants). Statistical heterogeneity was evident only for rebleeding. Treatment with PPIs had no significant effect on mortality (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.74-1.40; number needed to treat [NNT], incalculable) but significantly reduced rebleeding (OR, 0.49; 95% CI, 0.37-0.65; NNT, 13) and the need for surgery (OR, 0.61; 95% CI, 0.48-0.78; NNT, 34) and repeated endoscopic treatment (OR, 0.32; 95% CI, 0.20-0.51; NNT, 10). Results were similar when analysis was confined to trials with adequate allocation concealment. Treatment with PPIs significantly reduced mortality in Asian trials (OR, 0.35; 95% CI, 0.16-0.74; NNT, 34) and in patients with active bleeding or a nonbleeding visible vessel (OR, 0.53; 95% CI, 0.31-0.91; NNT, 50). CONCLUSIONS: In ulcer bleeding, PPIs reduce rebleeding and the need for surgery and repeated endoscopic treatment. They improve mortality among patients at highest risk. PMID- 17352365 TI - The role of mammography in male patients with breast symptoms. AB - OBJECTIVE: To determine the contribution of mammography to the comprehensive clinical evaluation of men with breast symptoms. PATIENTS AND METHODS: We retrospectively reviewed the records of all men who underwent mammography between January 1, 2001, and December 31, 2004, at the Mayo Clinic In Jacksonville, Fla. Medical history, mammographic findings, and breast cancer diagnoses were assessed. RESULTS: A total of 198 men had 212 mammograms. Nine mammograms (from 9 different men) (4%) showed suspicious findings. Eight men underwent biopsy, which yielded a breast cancer diagnosis in 2 (1%). Of the 212 mammograms, 203 (96%) showed benign findings, including gynecomastia on 132 (62%). One patient with a benign-appearing mammogram later underwent breast biopsy, and malignant disease was diagnosed. All the men with breast cancer had a dominant mass on clinical examination and other findings suggestive of breast cancer. Of the 132 mammograms showing gynecomastia, 110 (83%) were from men who had taken predisposing medications or who had predisposing medical conditions. CONCLUSIONS: Mammography added little information to the initial patient evaluation. Breast cancer may be suspected by the presence of a dominant mass. Gynecomastia can be predicted on the basis of the patient's symptoms or preexisting condition. Patients with suspicious findings on examination warrant appropriate clinical management regardless of mammographic findings. Mammography in men may be of benefit only for image guidance of percutaneous biopsy of a suspicious mass. PMID- 17352366 TI - Relationship between age-related macular degeneration-associated variants of complement factor H and LOC387715 with coronary artery disease. AB - OBJECTIVE: To determine whether either of the gene variants associated with age related macular degeneration is associated with coronary artery disease (CAD). PATIENTS AND METHODS: This study consisted of 493 patients who underwent clinically indicated coronary angiography between June 1, 1998, and January 1, 1999. The Y402H variant of the complement factor H (CFH) gene and the A69S variant of the LOC387715 gene locus were examined by restriction fragment length polymorphism. Multiple logistic regression models were used to assess the association of CFH and LOC gene variants with CAD. Covariates with well established associations with CAD were also evaluated. RESULTS: Seventy patients (14%) were homozygous for the histidine variant (HH) of CFH, 237 (48%) were heterozygous for the histidine variant (HY), and 186 (38%) were homozygous for the tyrosine variant (YY). Three hundred eight patients (62%) were homozygous for the alanine allele of LOC387715, 170 (34%) were heterozygous for Ala and Ser alleles, and 15 (3%) were homozygous for the serine variant. The overall association of the CFH genotype with CAD was not statistically significant (P=.08). However, some evidence (P=-.046) suggested that CAD was increased for the HH genotype compared to the homozygous wild-type YY genotype (odds ratio, 1.95; 95% confidence interval, 1.01-3.76). Male sex, hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and age were other variables that demonstrated significant associations with CAD. The overall effect of the LOC genotype was not statistically significant (P=-.06). Heterozygosity for the serine variant was (P=-.02) associated with the absence of CAD vs the AS genotype (odds ratio, 0.59; confidence interval, 0.38-0.91; P=-.02). CONCLUSION: The CFH genotype may have an independent association with CAD, although our evidence did not show statistical significance. Controlling for known risk factors, the age-related macular degeneration-associated HH variant appears to be associated with CAD. The LOC387715 gene may also play a role in CAD. PMID- 17352367 TI - Postural orthostatic tachycardia syndrome: the Mayo clinic experience. AB - OBJECTIVE: To evaluate the prevalence and pathogenetic mechanisms of postural orthostatic tachycardia syndrome (POTS). PATIENTS AND METHODS: We reviewed the medical records of patients with POTS seen at the Mayo Clinic in Rochester, Minn, from January 1, 1993, through December 31, 2003. All patients were required to have had a full autonomic reflex screen. The results of the following additional tests were evaluated: thermoregulatory sweat test, plasma catecholamine measurement, serum ganglionic (a3) acetylcholine receptor antibody detection, and 24-hour urinary sodium measurement. RESULTS: We identified 152 patients (86.8% female; mean +/- SD age, 30.2+/-10.3 years) with a mean duration of symptoms of 4.1 years. The mean orthostatic heart rate increment was 44 beats/min. Half the patients had sudomotor abnormalities (apparent on both the quantitative sudomotor axon reflex test and thermoregulatory sweat test), and 34.9% had significant adrenergic impairment, indicating that at least half of the patients had a neuropathic pattern of POTS. In 13.8% of patients, onset was subacute, and ganglionic acetylcholine receptor antibody was detected in 14.6%, suggesting an autoimmune origin in at least 1 in 7 patients. Hyperadrenergic status was documented in 29.0% of patients (standing plasma norepinephrine level 2600 pg/mL), and at least 28.9% were presumably hypovolemic (24-hour urinary sodium level <100 mEq/24h). The lack of correlation between urinary sodium and standing norepinephrine levels suggests that mechanisms other than hypovolemia accounted for the hyperadrenergic state. CONCLUSION: Our findings suggest a neuropathic basis for at least half the cases of POTS and that a substantial percentage of cases may be autoimmune. Hyperadrenergic and hypovolemic correlates are likely compensatory or exacerbating. PMID- 17352368 TI - Electronic article surveillance systems and interactions with implantable cardiac devices: risk of adverse interactions in public and commercial spaces. AB - Electronic article surveillance (EAS) systems are widely implemented in public spaces and can adversely affect the performance of pacemakers and implantable cardioverter defibrillators. The interaction between implantable devices and EAS systems is a serious problem that can be minimized through appropriate facility design. Careful facility design and employee education along with patient vigilance remain imperative in avoiding potentially life-threatening EAS system implantable device interactions. PMID- 17352369 TI - Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statement. AB - Multiple myeloma is a neoplastic plasma cell dyscrasia that on a yearly basis affects nearly 17,000 individuals and kills more than 11,000. Although no cure exists, many effective treatments are available that prolong survival and improve the quality of life of patients with this disease. The purpose of this consensus is to offer a simplified, evidence-based algorithm of decision making for patients with newly diagnosed myeloma. In cases in which evidence is lacking, our team of 18 Mayo Clinic myeloma experts reached a consensus on what therapy could generally be recommended. The focal point of our strategy revolves around risk stratification. Although a multitude of risk factors have been identified throughout the years, including age, tumor burden, renal function, lactate dehydrogenase, beta2-microglobulin, and serum albumin, our group has now recognized and endorsed a genetic stratification and patient functional status for treatment. PMID- 17352370 TI - Pulmonary hypertension in patients with interstitial lung diseases. AB - Pulmonary hypertension (PH) in patients with interstitial lung diseases (ILDs) is not well recognized and can occur in the absence of advanced pulmonary dysfunction or hypoxemia. To address this topic, we identified relevant studies in the English language by searching the MEDLINE database (1966 to November 2006) and by individually reviewing the references of identified articles. Connective tissue disease-related ILD, sarcoidosis, idiopathic pulmonary fibrosis, and pulmonary Langerhans cell histiocytosis are the ILDs most commonly associated with PH. Pulmonary hypertension is an underrecognized complication in patients with ILDs and can adversely affect symptoms, functional capacity, and survival. Pulmonary hypertension can arise in patients with ILDs through various mechanisms, Including pulmonary vasoconstriction and vascular remodeling, vascular destruction associated with progressive parenchymal fibrosis, vascular inflammation, perivascular fibrosis, and thrombotic angiopathy. Diagnosis of PH in these patients requires a high index of suspicion because the clinical presentation tends to be nonspecific, particularly in the presence of an underlying parenchymal lung disease. Doppler echocardiography is an essential tool in the evaluation of suspected PH and allows ready recognition of cardiac causes. Right heart catheterization is needed to confirm the presence of PH, assess its severity, and guide therapy. Management of PH in patients with ILDs is guided by identification of the underlying mechanism and the clinical context. An increasing number of available pharmacologic agents in the treatment of PH allow possible treatment of PH in some patients with ILDs. Whether specific treatment of PH in these patients favorably alters functional capacity or outcome needs to be determined. PMID- 17352371 TI - Nonsurgical management of primary hyperparathyroidism. AB - Primary hyperparathyroidism is the most common cause of hypercalcemia in the outpatient setting and is typically caused by a single benign parathyroid adenoma. Most patients with hyperparathyroidism are postmenopausal women. Patients can be asymptomatic or minimally symptomatic. Parathyroidectomy is the definitive cure for primary hyperparathyroidism, and no medical therapies have been approved by the Food and Drug Administration for this disorder. Guidelines for surgery have been established by a National Institutes of Health consensus panel, but many patients do not meet these guidelines or have comorbid conditions that prohibit surgery. This review describes alternative treatment options for patients who decide against or are unable to proceed with surgery. PMID- 17352372 TI - 25-year-old man with abdominal pain, nausea, and fatigue. PMID- 17352373 TI - Malignant melanoma in the 21st century, part 1: epidemiology, risk factors, screening, prevention, and diagnosis. AB - Malignant melanoma is an aggressive, therapy-resistant malignancy of melanocytes. The incidence of melanoma has been steadily increasing worldwide, resulting in an increasing public health problem. Exposure to solar UV radiation, fair skin, dysplastic nevi syndrome, and a family history of melanoma are major risk factors for melanoma development. The interactions between genetic and environmental risk factors that promote melanomagenesis are currently the subject of ongoing research. Avoidance of UV radiation and surveillance of high-risk patients have the potential to reduce the population burden of melanoma. Biopsies of the primary tumor and sampling of draining lymph nodes are required for optimal diagnosis and staging. Several clinically relevant pathologic subtypes have been identified and need to be recognized. Therapy for early disease is predominantly surgical, with a minor benefit noted with the use of adjuvant therapy. Management of systemic melanoma is a challenge because of a paucity of active treatment modalities. In the first part of this 2-part review, we discuss epidemiology, risk factors, screening, prevention, and diagnosis of malignant melanoma. Part 2 (which will appear in the April 2007 issue) will review melanoma staging, prognosis, and treatment. PMID- 17352374 TI - Atrial flutter simulated by a portable compact disk player. PMID- 17352375 TI - Rapid correction of severe hyponatremia after computed tomography with intravenous contrast. PMID- 17352376 TI - Association between oral contraceptive use and premenopausal breast cancer: mediated by hormonal confounders? PMID- 17352377 TI - Quality of life in obsessive-compulsive disorder: an evaluation of impairment and a preliminary analysis of the ameliorating effects of treatment. AB - Despite the substantial impairments in life functioning associated with obsessive compulsive disorder (OCD), treatment outcome evaluations have focused almost exclusively on symptom reduction, a focus that may be too narrow to determine whether clinically significant change has occurred. Quality of life (QOL) impairment was evaluated in a clinical OCD sample (N=188) using a multidimensional life satisfaction measure. Relationships between treatment response and QOL change also were evaluated with a subsample of participants (n=120). Congruent with previous studies of OCD, substantial pretreatment QOL impairment was found across all life domains. Distinct treatment change subgroups were identified: a group reporting strong symptom reduction and very good QOL gains, a second group with significant symptom reduction but less robust QOL improvements, and a third group with limited symptom gains and QOL decreases. Implications for understanding OCD-related impairment and the clinical significance of treatment outcomes are discussed. PMID- 17352378 TI - Relaxation and susceptibility MRI characteristics in Hallervorden-Spatz syndrome. AB - PURPOSE: To evaluate the imaging characteristics of the brain with respect to relaxation and susceptibility in Hallervorden-Spatz syndrome (HSS), a rare inherited neurodegenerative disorder (also referred to as neurodegeneration with brain iron accumulation). MATERIALS AND METHODS: We reviewed 13 affected individuals who satisfied the inclusion criteria for HSS. Clinically, the patients were divided into two groups: early-childhood onset (age of onset before 10 years) and late-childhood onset (age of onset after 10 years). MRI was performed on 1.5T MR equipment. The imaging protocol included spin-echo (SE) T1 weighted (T1W), turbo spin-echo (TSE) T2W, and fluid attenuated inversion recovery (FLAIR) sequences in all patients. Susceptibility-weighted imaging (SWI) included a fast low-angle shot (FLASH) sequence in 10 patients and a blood oxygen level-dependent (BOLD) sequence in two patients. RESULTS: All of the patients showed hyperintensity on T1WI and hypointensity on T2WI in the globus pallidi (GPs) bilaterally. Central or anteromedial hyperintensity was found in all but one patient. FLASH showed augmented hypointensity in 10 patients, and BOLD showed bilateral striatonigral abnormal pigmentation in two patients. MR spectroscopy (MRS) showed normal spectra in four patients, and a reduced NAA/Cho ratio in two. CONCLUSION: MRI showed prominent signal abnormalities in the GP bilaterally in HSS. T1WI showed hyperintensity in all cases of HSS in addition to the "eye-of the-tiger" sign on T2WI. SWI, FLASH, and BOLD demonstrated mineral deposition in the GP better than conventional imaging. Involvement of the striatonigral pathways was demonstrated for the first time on BOLD SWI. PMID- 17352379 TI - Depressive personality disorder, dysthymia, and their relationship to perfectionism. AB - This paper reports the results of two studies in a nonclinical (n=105) and primary care outpatient sample (n=110), in which Depressive Personality Disorder (DPD), Dysthymia, and depression were assessed for their distinctive relationship with perfectionism. Results from both studies found that self-reported DPD, Dysthymia, and depressive symptoms were all intercorrelated, and that DPD, Dysthymia, and depressive symptoms were correlated with three dimensions of perfectionism-Concern over Mistakes, Doubts about Actions, and Parental Criticism. In the nonclinical sample, variance in measures of DPD was predicted by measures of perfectionism after controlling for depression and Dysthymia symptoms. A similar pattern of findings was observed in the primary care sample. This relationship with perfectionism did not occur when Dysthymia or depressive symptoms were predicted. Nevertheless, much of the variance in measures of DPD, Dysthymia, and depressive symptoms is associated with each other and not perfectionism. It is concluded that a common factor or set of factors underlies these disorders, but that DPD may be more strongly related to perfectionism than Dysthymia and depression. As a common factor(s) is identified, measures of DPD and Dysthymia may be refined, thereby increasing the discriminant validity of their measures. PMID- 17352380 TI - Learning and memory impairment in PTSD: relationship to depression. AB - Memory function was studied in combat veterans with posttraumatic stress disorder (PTSD), combat veterans without PTSD, and noncombat veterans. The Vocabulary and Digit Span subtests of the WAIS and Logical Memory (LMS) and Verbal Paired Associates (VPAS) subtests of the Wechsler Memory Scale III were administered. Combat veterans with PTSD showed impaired memory on the LMS and VPAS compared to combat veterans without PTSD or noncombat veterans. Veterans with PTSD also showed lower WAIS Vocabulary subtest scores--but not digit span subtest scores- than combat veterans without PTSD or noncombat veterans. Medication status, co morbid diagnosis, and age all failed to account for these memory differences, but when self-assessed depression--as measured by the Zung Self-Rating Depression Scale--or anxiety--as measured by the Spielberger State-Trait Anxiety Scale--was statistically removed, group differences on these memory measures were no longer significant. However, using a stepwise regression procedure, in which both anxiety and depression were employed to predict the LMS and VPAS scores, only the Zung scale reliably predicated performance. The present results, showing that PTSD is associated with general learning and memory impairments, is an important finding, but the specific effects of depression as a mediator of these deficits should be further studied. PMID- 17352381 TI - C-reactive protein: informative or misleading marker of Crohn's disease? PMID- 17352382 TI - Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. AB - The role of NADPH oxidase (NOX) and the regulatory subunit p47(phox) for hypoosmotic ROS generation was studied in cultured rat astrocytes and brain slices of wilde type and p47(phox) knock-out mice. Cultured rat astrocytes express mRNAs encoding for the regulatory subunit p47(phox), NOX1, 2, and 4, and the dual oxidases (DUOX)1 and 2, but not NOX3. Hypoosmotic (205 mosmol/L) swelling of cultured astrocytes induced a rapid generation of ROS that was accompanied by serine phosphorylation of p47(phox) and prevented by the NADPH oxidase inhibitor apocynin. Apocynin also impaired the hypoosmotic tyrosine phosphorylation of Src. Both, hypoosmotic ROS generation and p47(phox) serine phosphorylation were sensitive to the acidic sphingomyelinase inhibitors AY9944 and desipramine, the protein kinase C (PKC)zeta-inhibitory pseudosubstrate peptide, the NMDA receptor antagonist MK-801 and the intracellular Ca(2+) chelator BAPTA-AM. Also hypoosmotic exposure of wilde type mouse cortical brain slices increased ROS generation, which was allocated in part to the astrocytes and which was absent in presence of apocynin and in cortical brain slices from p47(phox) knock-out mice. Also ammonia induced a rapid ROS production in cultured astrocytes and brain slices, which was sensitive to apocynin. The data suggest that astrocyte swelling triggers a p47(phox)-dependent NADPH oxidase-catalyzed ROS production. The findings further support a close interrelation between osmotic and oxidative stress in astrocytes, which may be relevant to different brain pathologies including hepatic encephalopathy. PMID- 17352384 TI - MR colonography without bowel purgation for the assessment of inflammatory bowel diseases: diagnostic accuracy and patient acceptance. AB - BACKGROUND: The purpose of this pilot study was to assess the diagnostic accuracy of MR colonography (MRC) without bowel cleansing regarding its ability to quantify inflammatory bowel disease (IBD). In addition, patient acceptance was compared with conventional colonoscopy (CC). METHODS: In all, 29 patients with IBD (17 ulcerative colitis; 12 Crohn's disease) were included. While CC was performed after bowel cleansing as the gold standard, MRC was based on a fecal tagging technique and performed 48-72 hours prior to CC. The presence of inflammation in each of 7 ileocolonic segments was rated for every procedure. Patients evaluated both modalities and dedicated aspects of the examination according to a 10-point-scale (1 = good, 10 = poor acceptance). Furthermore, preferences for future examinations were investigated. RESULTS: Inflammatory segments were found by means of CC in 23 and by MRC in 14 patients. Overall sensitivity and specificity of MRC in a segment-based detection were 32% and 88%, respectively. Concerning severely inflamed segments, sensitivity increased to 53% for MRC. Overall acceptance of CC was significantly higher compared to MRC (mean value (mv) for MRT = 6.0; CC = 4.1; P = 0.003). For MRC, the placement of the rectal tube (mv = 7.3), and for CC bowel purgation (mv = 6.5), were rated as the most unpleasant. A total of 67% of patients voted for CC as the favorable tool for future examinations. CONCLUSIONS: The presented data indicate that 'fecal tagging MRC' is not suitable for an adequate quantification of inflammatory diseases of the large bowel. Furthermore, overall acceptance of endoscopic colonoscopy was superior to MRC. PMID- 17352383 TI - Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. AB - Paranodal axo-glial junctions are important for ion channel clustering and rapid action potential propagation in myelinated nerve fibers. Paranode formation depends on the cell adhesion molecules neurofascin (NF) 155 in glia, and a Caspr and contactin heterodimer in axons. We found that antibody to ganglioside GM1 labels paranodal regions. Autoantibodies to the gangliosides GM1 and GD1a are thought to disrupt nodes of Ranvier in peripheral motor nerves and cause Guillain Barre syndrome, an autoimmune neuropathy characterized by acute limb weakness. To elucidate ganglioside function at and near nodes of Ranvier, we examined nodes in mice lacking gangliosides including GM1 and GD1a. In both peripheral and central nervous systems, some paranodal loops failed to attach to the axolemma, and immunostaining of Caspr and NF155 was attenuated. K(+) channels at juxtaparanodes were mislocalized to paranodes, and nodal Na(+) channel clusters were broadened. Abnormal immunostaining at paranodes became more prominent with age. Moreover, the defects were more prevalent in ventral than dorsal roots, and less frequent in mutant mice lacking the b-series gangliosides but with excess GM1 and GD1a. Electrophysiological studies revealed nerve conduction slowing and reduced nodal Na(+) current in mutant peripheral motor nerves. The amounts of Caspr and NF155 in low density, detergent insoluble membrane fractions were reduced in mutant brains. These results indicate that gangliosides are lipid raft components that contribute to stability and maintenance of neuron-glia interactions at paranodes. PMID- 17352385 TI - Ethical issues concerning therapeutic studies in inflammatory bowel disease. AB - Physicians often take on responsibilities beyond medical care regarding their patients with ulcerative colitis and Crohn's disease: they serve as the patients' advocates to nonmedical entities and individuals, including insurance companies, schools, employers, companions, and family members. These responsibilities create a more complex relationship between the patient and their IBD physician. In addition, these responsibilities may accentuate ethical issues for the physician who is also engaged in clinical treatment trials for inflammatory bowel disease (IBD). Ethical issues include therapeutic misconception, clinical equipoise, and financial and nonfinancial conflicts of interest. Physicians who refer patients with IBD to enroll in treatment trials, as well as clinician investigators who conduct studies should consider measures to clarify the separation between clinical care and participation in a therapeutic study, and to ensure the ethical treatment of patients. These precautionary measures may include payment of participants to emphasize that the research study is different from clinical care, consent by an investigator other than the treating physician, and care to disclose conflicts of interest to the patient and the medical community in presentations and publications. If the financial conflict is too great, a physician should not participate in the clinical trial. PMID- 17352386 TI - 5-Aminosalicylic acid (mesalazine) use in Crohn's disease: a survey of the opinions and practice of Australian gastroenterologists. AB - BACKGROUND: The use of 5-aminosalicylate (5-ASA) drugs in Crohn's disease (CD) is controversial, with their continuing apparent widespread use despite high-level evidence indicating marginal benefit at best and international guidelines recommending limited indications. METHODS: In order to understand how clinicians translate the evidence base into clinical practice, we surveyed a cross-section of Australian gastroenterologists to determine opinions and prescribing patterns of 5-ASA drugs in CD. RESULTS: In all, 42% of 285 gastroenterologists who were sent a questionnaire by e-mail responded. Five (4%) never use 5-ASA drugs in CD. The drugs are most commonly prescribed for patients with colonic (96%) or ileocolonic (92%) disease location, inflammatory disease behavior (80%), and mild disease activity (97%). The majority (64%) use a dose of 1-3 g/day, but only 6% use over 4.5 g/day. Less than one-half use 5-ASA drugs as maintenance following surgical resection, but most use it for inducing remission alone (70%) or in combination with other drugs (90%), and continue its use for maintenance. Side effects are thought to be infrequent (62%) or rare (20%) and few common side effects are believed to be serious. Respondents estimated that over 90% of patients were nonadherent to prescribed 5-ASA regimens at least 50% of the time. While 84% believed that 5-ASA drugs were effective in CD, only 58% believed that they were cost-effective. CONCLUSIONS: In Australia 5-ASA drugs are extensively prescribed for CD at relatively low doses without expectation of patient adherence. Current evidence and guidelines has had little apparent impact on clinical practice. The cost implications are considerable. PMID- 17352387 TI - Manitoba Oculotrichoanal (MOTA) syndrome: report of eight new cases. AB - The Manitoba Oculotrichoanal (MOTA) syndrome was initially described by Marles et al. [1992; Am J Med Genet 42: 793-799] in Aboriginal patients of the Island Lake region of Northern Manitoba. Characteristic findings in affected patients included unilateral upper eyelid coloboma or cryptophthalmus with ipsilateral aberrant anterior hairline pattern and anal anomalies. We describe here seven new patients of the same extended kindred of Cree/Ojibway ethnicity of the Island Lake region and an eighth patient of Caucasian Dutch parents with clinical findings consistent with the diagnosis of MOTA syndrome. Two of the patients have bilateral, instead of unilateral, abnormal anterior hairline patterns. Omphalocele, a feature previously not identified, is present in three of them. The most consistent features appear to be hypertelorism and a broad or notched tip of the nose. Due to the obvious clinical overlap with Fraser syndrome, FRAS1 gene was screened in two of the affected and no mutation was found [Slavotinek et al., submitted]. PMID- 17352388 TI - Clinical and molecular characterization of a patient with a 2q31.2-32.3 deletion identified by array-CGH. AB - We report on a patient with a de novo interstitial deletion of the long arm of chromosome 2 involving bands 2q31.2-2q32.3. The patient shows severe mental retardation, absence of speech, sleep disturbances, behavioral problems, and some dysmorphic features. In particular, he presents with macrocephaly, high forehead, thick and coarse hair, thick eyebrows, synophrys, increased inner and outer canthal distance, bifid nasal tip, high palate, micrognathia, dysmorphic right ear, and long and tapering fingers. Array-CGH analysis allowed us to identify and characterize a 2q interstitial deletion of about 13 Mb, involving the segment between cytogenetic bands 2q31.2 and 2q32.3. The deletion was confirmed by quantitative PCR. We compare the phenotype of our patient with those already reported in literature. In particular, we discuss the similarities shared with two recently reported patients, studied by array-CGH, who show an overlapping deletion. The common clinical features are: long face, high forehead, abnormal teeth and ears, midface hypoplasia, high palate, micrognathia, transparent and thin skin, high frequency of inguinal hernia, severe development impairment, and behavioral problems. Some genes located in the deleted region may be good candidates for the neurological phenotype such as ZNF533 and MYO1B, which are both involved in neuronal function. Furthermore, the GLS gene could be a good candidate in generating the behavioral phenotype in the patient. In fact, it encodes for the major enzyme yielding glutamate from glutamine and it can be implicated in behavioral disturbances in which glutamate acts as a neurotransmitter. PMID- 17352389 TI - Recurrent SOX9 deletion campomelic dysplasia due to somatic mosaicism in the father. AB - Haploinsufficiency of SOX9, a master gene in chondrogenesis and testis development, leads to the semi-lethal skeletal malformation syndrome campomelic dysplasia (CD), with or without XY sex reversal. We report on two children with CD and a phenotypically normal father, a carrier of a somatic mosaic SOX9 deletion. This is the first report of a mosaic deletion of SOX9; few familial CD cases with germline and somatic mutation mosaicism have been described. Our findings confirm the utility of aCGH and indicate that for a more accurate estimate of the recurrence risk for a completely penetrant autosomal dominant disorder, parental somatic mosaicism should be considered in healthy parents. PMID- 17352390 TI - Late onset Leigh syndrome and ataxia due to a T to C mutation at bp 9,185 of mitochondrial DNA. AB - A T-to-C missense mutation at nucleotide position 9,185 in the protein-coding ATP6 gene of the mitochondrial genome was present at high heteroplasmy in members of a Canadian family with Leigh syndrome with predominant ataxia and peripheral neuropathy. This mutation results in the substitution of a proline residue for an evolutionary-conserved leucine at position of amino acid 220 near the carboxyl terminus of the mitochondrial protein. The index patient and brother, who had an identical clinical presentation, had >90% mutant mtDNA in cultured skin fibroblasts, lymphocytes, and whole blood. Their mother and a maternal uncle, symptomatic with a peripheral neuropathy alone, had 86% and 85% heteroplasmy, respectively. Symptomatic maternal cousins with early onset revealed 90% and 91% mutant mtDNA in all tissues analyzed. Studies of lymphoblasts from the asymptomatic maternal grandmother and eldest brother of the proband were heteroplasmic for mutant mtDNA with 56% and 17%, respectively. Biochemical analysis demonstrated normal respiratory chain enzyme activity in muscle and fibroblasts, normal ATP synthesis, but reduced oligomycin-sensitive H(+)ATPase in cultured lymphoblast mitochondria. We propose that the 9,185T > C mtDNA mutation is pathogenic even though the initial phenotype is mild and the biochemical phenotype not easily detectable. PMID- 17352391 TI - "Zwilling" versus "Tai Chi" configuration of double-sized ring chromosome. PMID- 17352392 TI - Sequence variation in ultraconserved and highly conserved elements does not cause X-linked mental retardation. PMID- 17352393 TI - Screening and biochemical analysis of GATA4 sequence variations identified in patients with congenital heart disease. AB - Few known monogenic causes of non-syndromic congenital heart disease (CHD) have been identified. Mutations in NKX2.5 were initially implicated in familial cases of cardiac septal defects and subsequently, functionally significant NKX2.5 mutations were found in diverse forms of non-syndromic CHD. Similarly, mutations in GATA4, which encodes a cardiac transcription factor, were first identified in familial cases of cardiac septal defects. We hypothesize that individuals with non-syndromic CHD may harbor GATA4 mutations and that these mutations alter the biochemical properties of the protein. The coding region encompassing the six exons of GATA4 was screened in a study population of 157 patients with CHD. We identified several sequence variations in GATA4. We tested these novel sequence variations that altered evolutionarily conserved amino acids and other previously reported GATA4 mutations in various biochemical assays. The novel sequence variations had no biochemical deficits while a previously reported, but unstudied, missense mutation in GATA4 (S52F) functioned as a hypomorph in transactivation assays. We did not identify any novel GATA4 mutations in our patient population with non-syndromic CHD. Consistent with previous findings, GATA4 mutations that result in deficits in transactivation ability are consistently associated with CHD suggesting that normal transactivation properties of GATA4 are required for proper cardiac development. PMID- 17352394 TI - The ADULT-EEC spectrum: an R280C mutation with a borderline phenotype. PMID- 17352395 TI - Currarino syndrome shown by prenatal onset ventriculomegaly and spinal dysraphism. AB - The most frequent cause of ventriculomegaly is spina bifida when associated with Arnold-Chiari type II malformation. We report on a prenatal diagnosis of severe ventriculomegaly in association with spinal dysraphism that was indicative of a Currarino syndrome (CS) due to a c.584delA, p.H195fsX28 truncated mutation within the HLXB9 gene. Physiopathology of the ventriculomegaly is discussed in reference to the fetopathological examination and CS embryopathology. In the present case, prognosis was poor and pregnancy termination was authorized. However, such a decision may be controversial in fetuses with less severe malformations on sonographic examination, since mutations in the HLXB9 gene can predict neither the severity nor the long-term prognosis of the disease. Due to a lack of genotype-phenotype correlation and the broad variability of phenotype in heterozygotes, clinical and genetic investigations among relatives are mandatory in all HLXB9 gene mutation cases, to detect asymptomatic CS cases and to prevent the occurrence of severe complications. PMID- 17352396 TI - Hepatobiliary MRI: current concepts and controversies. AB - Evaluation of the liver and biliary system is a frequent indication for abdominal MRI. Hepatobiliary MRI comprises a set of noninvasive techniques that are usually very effective in answering most clinical questions. There are significant limitations, however, as well as considerable variation and disagreement regarding the optimal protocols for standard hepatic MRI and magnetic resonance cholangiopancreaticography (MRCP). This review discusses pulse sequences most often used in hepatic MRI and MRCP, examines a few sources of controversy in the current literature, and summarizes some recent and future developments in the field. PMID- 17352397 TI - Use of written treatment plans for asthma by specialist physicians. AB - Few studies have addressed use of written treatment plans (WTPs) for asthma by specialist physicians. The purpose of this study is to characterize the attitudes, beliefs, and self-reported practice behaviors regarding asthma WTP use among specialist physicians. Structured interviews were conducted with pulmonologists and allergists who provide direct patient asthma care in two New York City medical centers. The interview covered five areas: (1) demographic information; (2) experiences with WTPs; (3) reported clinical practice behaviors; (4) factors influencing use of WTPs; and (5) physician-patient communication. Forty-five physicians were eligible to participate in the study. Sixty-eight percent of physicians treated adult patients while 32% were pediatric specialists. Forty-four physicians completed interviews, (response rate of 98%). Eighty-six percent indicated they use WTPs with at least some of their patients (71% of their patients had received a plan from them). Most reported handwriting plans on a blank piece of paper (66%). Most plans were symptom-based (47%) or combined symptoms with peak flow measurement (50%). Most plans supported patient autonomy. More than 80% of physicians believe the use of a WTP improves patient outcomes. The results suggest that asthma specialists in this survey utilize WTPs more frequently than reported in other studies. Physicians encourage patient autonomy and believe asthma self-management by patients improves their outcomes. Controlled studies of the efficacy of asthma management plans are needed to assess the impact of WTPs as used in clinical practice. PMID- 17352398 TI - Cervical lymphadenitis due to mycobacterium interjectum. PMID- 17352399 TI - Acute life threatening event (ALTE) in an infant with human coronavirus HCoV-229E infection. AB - In this short report we discuss the temporal association between an acute life threatening event (ALTE) and a RT-PCR confirmed coronavirus HCoV-229E infection in a 4 months old otherwise healthy infant. More detailed microbiological investigations of affected children even without apparent signs of a respiratory tract infection may help to clarify the etiology in some patients and extend our understanding of the pathogenesis. PCR-based techniques should be utilized to increase the sensitivity of detection for old and new respiratory viral pathogens in comparable cases. PMID- 17352400 TI - The selling of Thomas Eakins. PMID- 17352401 TI - Variation of the spinal nerve compositions of thoracodorsal nerve. AB - Thoracodorsal nerve distributes to the latissimus dorsi muscle. The aim of this study was to investigate the anatomic variation of the spinal nerve compositions of thoracodorsal nerve and to confirm which spinal nerve is a main component in participating amount. The most frequent type was consisted of C7 and C8 in 60%. Next frequent type was C6, C7, and C8 in 25%. Third type was C6 and C7 in 10% and fourth type was C7 alone in 5%. The diameter of each spinal nerve comprising thoracodorsal nerve was 1.20 +/- 0.23 (mean +/- SD) mm at C7, 0.43 +/- 0.15 mm at C8, and 0.33 +/- 0.09 mm at C6. These results show that the C7 nerve was the main component of thoracodorsal nerve and the anatomic variation appeared at the spinal nerve that participate by small amounts, as be excepted (C6 and C8). PMID- 17352402 TI - Anomalous continuation of the left lateral testicular vein. PMID- 17352403 TI - Nocturnal body position in sleeping children with and without obstructive sleep apnea. AB - OBJECTIVES: To assess whether body position during sleep differs among children with obstructive sleep apnea (OSAS) and controls, and to assess the effects of body position, obesity, and tonsillar size on respiratory disturbance. Four hundred and thirty consecutive children with polysomnographically demonstrated OSAS. And 185 age-, gender-, and ethnically matched children (Controls) were compared. The effect of sleep body position on respiratory disturbance was examined in OSAS, and also in relation to obesity and tonsillar size. Children with OSAS spent more time in the supine position than Controls (P<0.01), with less time spent in the side position (P<0.005). Obstructive apnea and hypopnea index (AHI) was similar in the three sleep-related positions, but apnea index (AI) was significantly greater (4.6 +/- 0.7/hr TST) in the supine position than in the side position (2.7 +/- 0.3/hr TST; P<0.001) or prone position (3.3 +/- 0.5/hr TST; P<0.01). Tonsillar size was not a contributing factor to positional differences in AI or AHI. Obese OSAS children had increased prone position (20.4 +/- 2.0%TST vs. non-obese: 10.9 +/- 2.5%TST; P<0.05), and displayed increased AHI and AI while supine. Non-obese OSAS increased AHI in prone or side positions compared to supine (P<0.01), with no significant differences in position dependent AI. Children with OSAS spend more time sleeping supine and less time on the side. Obese children with OSAS are more likely to sleep prone, suggesting that this position may promote upper airway patency in the presence of obesity. Although tonsillar size is not associated with positional differences in breathing, the presence or absence of obesity markedly modifies the effect of body position on respiratory disturbance. PMID- 17352404 TI - Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety. AB - Aerosolized antibiotics are associated with a high treatment burden that can result in non-adherence to chronic therapy. We evaluated the pharmacokinetics (PK) and safety of tobramycin inhalation powder (TIP), a novel dry-powder formulation designed to deliver a high payload of tobramycin topically to the lungs for management of chronic Pseudomonas aeruginosa infections. This was a multi-center, open-label, sequential-cohort, single-dose, dose-escalation study using the standard 300 mg dose of tobramycin solution for inhalation (TSI) as an active control. Subjects were randomized to TIP or TSI in a 3:1 ratio in each of five cohorts. Measurements included serum and sputum tobramycin concentrations, administration time, serum chemistries, acute change in lung function, and adverse events (AEs). Out of 90 randomized subjects, 86 had data for safety analysis; and 84 had data for PK analysis. Serum tobramycin PK profiles were similar for TIP and TSI. Four capsules of 28 mg TIP (total tobramycin dose 112 mg) produced comparable systemic exposure to 300 mg TSI, in less than one-third the administration time. The most common AEs associated with TIP were cough (20%) and dysgeusia (17%). TIP allows for faster and more efficient pulmonary delivery of tobramycin than TSI and has a safety profile that supports continued clinical investigation. The increased rate of local respiratory tract irritation noted with TIP is not unexpected with a high-payload powder formulation. The development of dry powder inhaled antibiotics may represent an important advance in the treatment of chronic lung infections. PMID- 17352405 TI - High affinity interaction of integrin alpha4beta1 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) enhances migration of human melanoma cells across activated endothelial cell layers. AB - The capacity of tumor cells to form metastatic foci correlates with their ability to interact with and migrate through endothelial cell layers. This process involves multiple adhesive interactions between tumor cells and the endothelium. Only little is known about the molecular nature of these interactions during extravasation of tumor cells. In human melanoma cells, the integrin alphavbeta3 is involved in transendothelial migration and its expression correlates with metastasis. However, many human melanoma cells do not express beta3 integrins. Therefore, it remained unclear how these cells undergo transendothelial migration. In this study we show that human melanoma cells with different metastatic potency, which do not express beta2 or beta3 integrins, express the VCAM-1 receptor alpha4beta1. VCAM-1 is up-regulated on activated endothelial cells and is known to promote transendothelial migration of leukocytes. Interestingly, despite comparable cell surface levels of alpha4beta1, only the highly metastatic melanoma cell lines MV3 and BLM, but not the low metastatic cell lines IF6 and 530, bind VCAM-1 with high affinity without further stimulation, and are therefore able to adhere to and migrate on isolated VCAM-1. Moreover, we demonstrate that function-blocking antibodies against the integrin alpha4beta1, as well as siRNA-mediated knock-down of the alpha4 subunit in these highly metastatic human melanoma cells reduce their transendothelial migration. These data imply that only high affinity interactions between the integrin alpha4beta1 on melanoma cells and VCAM-1 on activated endothelial cells may enhance the metastatic capacity of human beta2/beta3-negative melanoma cells. PMID- 17352406 TI - The role of the Cdk9/Cyclin T1 complex in T cell differentiation. AB - The Cdk9/Cyclin T1 complex is very important in controlling specific differentiative pathways of several cell types, including muscle cells and neurons. We recently demonstrated the involvement of this complex in B cell activation/differentiation. To check whether the Cdk9/Cyclin T1 complex is also involved in the T cell activation/differentiation process, we isolated different T cell populations by magnetic separation, based on their surface antigens. We observed that the expression level of Cdk9/Cyclin T1 increases in effector T cells (CD27(+)), as well as in activated T cells (CD25(+)) and memory T cells (CD45RA(-)), thus suggesting a specific upregulation of the Cdk9/Cyclin T1 complex following antigen encounter. We have previously demonstrated that in B cells, Cdk9 interacts in vivo with the E2A gene products E12/E47 (members of the basic helix-loop-helix family) which are involved in differentiation. In this article, we show that this interaction also occurs in T cells. This suggests an active role for the Cdk9/Cyclin T1 complex during lymphoid differentiation, through physical binding with E12 and E47. These preliminary results suggest that the Cdk9/Cyclin T1 complex may be important in the activation and differentiation program of lymphoid cells and that its upregulation, which is due to still unknown mechanisms, may contribute to malignant transformation. PMID- 17352407 TI - Transitional CpG methylation between promoters and retroelements of tissue specific genes during human mesenchymal cell differentiation. AB - In general, methylation of the promoter regions is inversely correlated with gene expression. The transitional CpG area between the promoter-associated CpG islands and the nearby retroelements is often methylated in a tissue-specific manner. This study analyzed the relationship between gene expression and the methylation of the transitional CpGs in two human stromal cells derived from the bone marrow (BMSC) and adipose tissue (ATSC), both of which have a multilineage differentiation potential. The transitional CpGs of the osteoblast-specific (RUNX2 and BGLAP), adipocyte-specific (PPARgamma2), housekeeping (CDKN2A and MLH1), and mesenchyme-unrelated (RUNX3) genes were examined by methylation specific PCR. The expression of each gene was measured using reverse transcription PCR analysis. The RUNX2, BGLAP, and CDKN2A genes in the BMSC, and the PPARgamma2 gene in the ATSC exhibited hypomethylation of the transitional CpGs along with the strong expression. The CpG island of RUNX3 gene not expressed in both BMSC and ATSC was hypermethylated. Transitional hypomethylation of the MLH1 gene was accompanied by the higher expression in the BMSC than in the ATSC. The weakly methylated CpGs of the PPARgamma2 gene in the BMSC became hypomethylated along with the strong expression during the osteoblastic differentiation. There were no notable changes in the transitional methylation and expression of the genes other than PPARgamma2 after the differentiation. Therefore, the transitional methylation and gene expression established in mesenchymal cells tend to be consistently preserved under the induction of differentiation. Weak transitional methylation of the PPARgamma2 gene in the BMSC suggests a methylation-dependent mechanism underlying the adiopogenesis of bone marrow. PMID- 17352408 TI - Insulin down-regulates TRAIL expression in vascular smooth muscle cells both in vivo and in vitro. AB - To dissect the effect of hyperinsulinemia versus hyperglycemia on TNF-related apoptosis inducing ligand (TRAIL) expression in the macrovascular district, we measured TRAIL mRNA and protein in four groups of animals: streptozotocin (SZT) induced diabetic rats, vehicle-treated control animals, diabetic rats treated with insulin and non-diabetic rats treated with insulin. While the aortas of diabetic rats did not show significant differences in TRAIL expression with respect to vehicle-treated control animals, the aortas of both diabetic and non diabetic rats treated in vivo for 16 days with insulin showed a significant decrease in TRAIL expression with respect to either diabetic and control rats. Moreover, in vitro treatment of both rat and human vascular smooth muscle cells (VSMC) with insulin induced the down-regulation of TRAIL protein. While the addition of recombinant TRAIL to rat VSMC promoted the dose-dependent release of bioactive nitric oxide (NO), this effect was significantly counteracted by pre exposure of VSMC to insulin. These findings suggest that TRAIL might act as an endogenous regulator of the vascular tone and that chronic elevation of insulin might contribute to the vascular abnormalities characterizing type-2 diabetes mellitus by down-regulating TRAIL expression and activity. PMID- 17352410 TI - The vertebral nerve revisited. AB - There is significant paucity in the literature regarding the vertebral nerve. Moreover, descriptions of this structure are conflicting. To evaluate further the anatomy and potential clinical significance of this structure, 10 fresh adult cadavers (20 sides) underwent dissection and macroscopic observation of this structure. All specimens were found to have a vertebral nerve that originated from the stellate ganglion with the exception of two left sides (10%) in which this nerve arose from the inferior cervical ganglion. This nerve ascended posteromedial to the vertebral artery. The vertebral nerve was found to be, in essence, a long and deep gray ramus communicans that connected most commonly the stellate ganglia to C6 or C7 spinal nerves by passing through the C6 and C7 transverse foramina. Fifteen percent of sides were found to have a vertebral nerve that was plexiform in its configuration. Fifty percent were found to have very small branches that entered the fibrous capsule of adjacent zygapophyseal and intervertebral joints. Some specimens were noted to have meningeal branches of the vertebral nerve. Based on our observations, the vertebral nerve is simply a deep ramus communicans, which often provides articular and meningeal branches to the adjacent spine. As neck pain is a significant reason for physician office visits, additional knowledge of the nerves innervating the joints and adjacent meninges of the neck could be important for both surgical and medical blockade of nerve fibers. PMID- 17352411 TI - Lucja Frey: a pioneering physician in tragic times. PMID- 17352409 TI - Neutrophil-activating protein-2- and interleukin-8-mediated angiogenesis. AB - In this study, we investigated the anti-angiogenic potential of nitric oxide (NO) donors and anti-integrin compounds against neutrophil-activating protein-2 (NAP 2), interleukin-8 (IL-8), and basic fibroblast growth factor (FGF-2)-induced angiogenesis. In vivo, recombinant human NAP-2 and FGF-2 induce a potent and comparable angiogenic response in the chick embryo chorioallantoic membrane (CAM). We demonstrate that NO donors and anti-integrin agents are capable of abrogating either NAP-2- or FGF-2-induced angiogenesis in the CAM model. The NO donor, S-nitroso N-acetyl penicillamine (SNAP), blocked either NAP-2- or FGF-2 mediated angiogenesis in the CAM. Similarly, angiogenesis stimulated with NAP-2 or FGF-2 was blocked by antagonist of the alphavbeta3 integrin in the CAM model. However, the inhibition of NAP-2 and IL-8 by the anti-integrin compound is significantly less than the inhibition observed with FGF-2 as the angiogenic stimulus. Similarly, the ability of these mechanisms to also inhibit endothelial cell differentiation was demonstrated. Taken together, these data illustrate the involvement of multiple pathways in the mechanisms of action for the alpha chemokine- and cytokine-mediated angiogenesis. These approaches may be a useful tool for the inhibition of angiogenesis associated with human tumor growth or with neovascular, ocular, and inflammatory diseases where chemokines and cytokines are involved. PMID- 17352412 TI - Anatomic variation of the 5th extensor tendon compartment and extensor digiti minimi tendon. AB - Anatomic variation within the 5th extensor compartment may contribute to the development of tenosynovitis and limit the usefulness of the extensor digiti minimi (EDM) for tendon transfer. The purpose of this study was to assess the anatomic variation of the EDM tendon and its surrounding retinaculum, with particular attention to anatomical variation between specimens. Forty-one fresh cadaver hands were dissected. The length of the 5th compartment retinaculum was noted. The incidence of an intercompartmental septum was noted in each specimen as well as the type of tendinous attachments present between the EDM and extensor digitorum communis (EDC) tendons. The presence and length of any accessory retinacular bands distal to the edge of proper extensor retinaculum was also noted. Only one specimen contained a single EDM tendon, while 71% (n = 29) of specimens contained two slips and 23% (n = 9) had three slips; 24% (n = 10) of EDC tendons had no slip to the small finger, while 61% (n = 25) of specimens had a single slip to the small finger. The EDC's contribution to the small finger was found to be an independent tendon in 42% of cases (n = 17), while 34% (n = 14) of specimens were found to have a common EDC slip, which branched to both the ring and small finger. Three EDM tendons divided distal to the extensor retinaculum, while the remaining EDM tendons divided beneath or proximal to the extensor retinaculum. Seventy-three percent (n = 30) of the specimens had an accessory retinacular band surrounding the EDM tendon identified at the base of the 5th metacarpal. Eighty-eight percent (n = 36) of hands had a septum between the EDM slips. The surgeon should be aware of variability within the 5th dorsal compartment in cases of trauma and in cases of tendon transfer. In our series 30 of 41 specimens were noted to contain an accessory dorsal retinacular band surrounding the EDM and 36 specimens were noted to contain a septum within the 5th compartment. The presence of an accessory retinacular band surrounding the EDM at the level of the 5th metacarpal base is an anatomic finding that requires further investigation. PMID- 17352413 TI - Sensory innervation of mandibular teeth by the nerve to the mylohyoid: implications in local anesthesia. AB - Traditionally, the nerve to the mylohyoid has been considered a motor nerve. However, dissection and clinical studies have challenged this dogma implicating the nerve to the mylohyoid as a nerve of accessory sensory innervation to mandibular teeth. Within the infratemporal fossa, the nerve to the mylohyoid branches from the inferior alveolar nerve and may be anesthetized with an inferior alveolar nerve block. However, because of the variability in location of branching and the potential barriers formed by both the pterygomandibular fascia and the sphenomandibular ligament, the nerve to the mylohyoid may escape anesthesia in an inferior alveolar nerve block. This may prevent profound local anesthesia of the mandibular teeth and may account, at least in part, for the high failure rate of the inferior alveolar nerve block. Alternative local anesthesia procedures may be employed to ensure adequate anesthesia of the nerve to the mylohyoid is achieved. This review provides a background of anatomical and clinical research of the nerve to the mylohyoid and outlines techniques suggested for providing a neural blockade of the nerve to the mylohyoid. PMID- 17352415 TI - Response to the letter to the editor from Papaloucas et al.: additional renal arteries. PMID- 17352414 TI - Anatomy and quantitation of the subscapular nerves. AB - Information regarding branches of the brachial plexus can be of utility to the surgeon for neurotization procedures following injury. Sixty-two adult cadaveric upper extremities were dissected and the subscapular nerves identified and measured. The upper subscapular nerve originated from the posterior cord in 97% of the cases and in 3% of the cases directly from the axillary nerve. The upper subscapular nerve originated as a single nerve in 90.3% of the cases, as two independent nerve trunks in 8% of the cases and as three independent nerve trunks in 1.6% of the cases. The thoracodorsal nerve originated from the posterior cord in 98.5% of the cases and in 1.5% of the cases directly from the proximal segment of the radial nerve. The thoracodorsal nerve always originated as a single nerve from the brachial plexus. The lower subscapular nerve originated from the posterior cord in 79% of the cases and in 21% of the cases directly from the proximal segment of the axillary nerve. The lower subscapular nerve originated as a single nerve in 93.6% of the cases and as two independent nerve trunks in 6.4% of the cases. The mean length of the lower subscapular nerve from its origin until it provided its branch into the subscapularis muscle was 3.5 cm and the mean distance from this branch until its termination into the teres major muscle was 6 cm. The mean diameter of this nerve was 1.9 mm. The mean length of the upper subscapular nerve from its origin to its termination into the subscapularis muscle was 5 cm and the mean diameter of the nerve was 2.3 mm. The mean length of the thoracodorsal nerve from its origin to its termination into the latissimus dorsi muscle was 13.7 cm. The mean diameter of this nerve was 2.6 mm. Our hopes are that these data will prove useful to the surgeon in surgical planning for potential neurotization procedures of the brachial plexus. PMID- 17352416 TI - Three-dimensional study of the musculotendinous architecture of supraspinatus and its functional correlations. AB - The supraspinatus is most frequently involved in shoulder pathology. However, the musculotendinous architecture of the supraspinatus has not been well documented. Therefore, the purpose of this study is to investigate the detailed three dimensional architecture of the supraspinatus throughout its volume. Ten male formalin embalmed cadaveric specimens (mean age 61.9 +/- 16 years) without any evidence of rotator cuff pathology were used. Three-dimensional coordinates (x, y, and z) of the tendon and muscle fiber bundles were collected in situ, using serial dissection and digitization. The data was reconstructed into a three dimensional model using Maya. Fiber bundle lengths, pennation angles (PA), muscle volumes, and tendon dimensions for each architecturally distinct area were computed and then analyzed using paired t-tests and ANOVA (P < 0.05). The supraspinatus was found to consist of anterior and posterior regions, which were each further subdivided into superficial, middle, and deep parts. Mean PA were found to be significantly different between the distinct parts of the anterior region of the muscle. Medial PA was also found be significantly different between the superficial and middle, and superficial and deep parts of the posterior region. These results provide insight into the normal function of the muscle and its possible contribution to the initiation and progression of supraspinatus tendon tears. PMID- 17352417 TI - Microtubules' interaction with cell cortex is required for their radial organization, but not for centrosome positioning. AB - Microtubules in interphase mammalian cells usually form a radial array with minus ends concentrated in the central region and plus-ends placed at the periphery. This is accepted as correct, that two factors determinate the radial organization of microtubules - the centrosome, which nucleate and anchor the microtubules minus-ends, and the interaction of microtubules with cortical dynein, which positions centrosome in the cell center. However, it looks as if there are additional factors, affecting the radial structure of microtubule system. We show here that in aged Vero cytoplasts (17 h after enucleation) microtubule system lost radial organization and became chaotic. To clear up the reasons of that, we studied centrosome activity, its position in the cytoplasts and microtubule dynamics. We found that centrosome in aged cytoplasts was still active and placed in the central region of the cytoplasm, while after total disruption of the microtubules it was displaced from the center. Microtubules in aged cytoplasts were not stabilized, but they lost their ability to stop to grow near cell cortex and continued to grow reaching it. Aged cytoplast lamellae was partially depleted with dynactin though Golgi remained compact indicating dynein activity. We conclude that microtubule stoppage at cell cortex is mediated by some (protein) factors, and these factors influence radial structure of microtubule system. It seems that the key role in centrosome positioning is played by dynein complexes anchored everywhere in the cytoplasm rather than anchored in cell cortex. PMID- 17352420 TI - Development of a multistage classifier for a monitoring system of cell activity based on imaging of chromosomal dynamics. AB - BACKGROUND: Cell-based assays utilizing digital image cytometry yield multivariate sets of information measuring the efficacy of medicines/chemicals. The use of a HeLa cell line that expresses a GFP-Histone-H1 fusion protein further enhances the performance of these systems, avoiding the use of dyes that may have detrimental influence on cells. Aside from the mitotic index, the distribution of the cell-cycle phases during mitosis can be used as measures of drug/treatment efficacy. Quantification of these parameters, however, requires skill and is time consuming. The purpose of this research was therefore to create a classifier to be incorporated into a system that can automatically identify the cell-cycle phases in a given image. METHODS: Features based on the shape and texture of the chromosomal regions in images of live HeLa cells were measured and analyzed. Linear discriminant functions were calculated for the eight cell-cycle phases: interphase, prophase, prometaphase, metaphase, early anaphase, anaphase, telophase and cytokinesis. RESULTS: The multistage linear discriminant classifier developed had an average classification efficiency of 87.30%. CONCLUSION: We demonstrated the possibility of creating a classifier to discriminate between cell-cycle phases using shape and texture features of chromosomal regions. The classifier can be fused to an algorithm for image segmentation, forming a system to automatically and rapidly measure the aforementioned parameters. The results can then be collated to constitute an assay assessing the effects of a drug or treatment on mammalian cells. PMID- 17352418 TI - Analysis of the linkage of MYRIP and MYO7A to melanosomes by RAB27A in retinal pigment epithelial cells. AB - The apical region of the retinal pigment epithelium (RPE) typically contains melanosomes. Their apical distribution is dependent on RAB27A and the unconventional myosin, MYO7A. Evidence from studies using in vitro binding assays, melanocyte transfection, and immunolocalization have indicated that the exophilin, MYRIP, links RAB27A on melanosomes to MYO7A, analogous to the manner that melanophilin links RAB27A on melanocyte melanosomes to MYO5A. To test the functionality of this hypothesis in RPE cells, we have examined the relationship among MYRIP, RAB27A and MYO7A with studies of RPE cells in primary culture (including live-cell imaging), analyses of mutant mouse retinas, and RPE cell fractionation experiments. Our results indicate that the retinal distribution of MYRIP is limited to the RPE, mainly the apical region. In RPE cells, RAB27A, MYRIP, and MYO7A were all associated with melanosomes, undergoing both slow and rapid movements. Analyses of mutant mice provide genetic evidence that MYRIP is linked to melanosomes via RAB27A, but show that recruitment of MYRIP to apical RPE is independent of melanosomes and RAB27A. RAB27A and MYRIP also associated with motile small vesicles of unknown origin. The present results provide evidence from live RPE cells that the RAB27A-MYRIP-MYO7A complex functions in melanosome motility. They also demonstrate that RAB27A provides an essential link to the melanosome. PMID- 17352421 TI - Subject classification obtained by cluster analysis and principal component analysis applied to flow cytometric data. AB - BACKGROUND: Polychromatic flow cytometry (PFC) allows the simultaneous determination of multiple antigens in the same cell, resulting in the generation of a high number of subsets. As a consequence, data analysis is the main difficulty with this technology. Here we show the use of cluster analysis (CA) and principal component analyses (PCA) to simplify multicolor data visualization and to allow subjects' classification. METHODS: By eight-colour cytofluorimetric analysis, we investigated the T cell compartment in donors of different age (young, middle-aged, and centenarians). T cell subsets were identified by combining positive and negative expression of antigens. The resulting data set was organized into a matrix and subjected to CA and PCA. RESULTS: CA clustered people of different ages on the basis of cytofluorimetric profile. PCA of the cellular subsets identified centenarians within a different cluster from young donors, while middle-aged donors were scattered between these groups. These approaches identified T cell phenotypes that changed with increasing age. In young donors, memory T cell subsets tended to be CD127+ and CD95- whereas CD127-, CD95+ phenotypes were found at higher frequencies in people with advanced age. CONCLUSIONS: Our data suggest the use of bioinformatic approaches to analyze large data-sets generated by PFC and to obtain the rapid identification of key populations that best characterize a group of subjects. PMID- 17352422 TI - Genetic model testing and statistical power in population-based association studies of quantitative traits. AB - The optimal method for considering different genetic models in association studies is not clear. We compared analytical strategies that use different genetic models to analyze genotype-phenotype information from association studies of quantitative traits in unrelated individuals. We created simulated datasets where the minor alleles are causal with an additive, dominant, or recessive mode of inheritance over a range of allele frequencies. We then computed power to detect these causal alleles using one or a combination of statistical models in a standard regression framework, including corrections for the multiple testing incurred by analyzing multiple models. Our results show that, as expected, maximal power is achieved when we test a single genetic model that matches the actual underlying mode of inheritance of the causal allele. When the inheritance pattern of the causal allele is unknown, the co-dominant model, a single two degrees of freedom test, has good overall performance in any of the three simple modes of inheritance simulated. Alternatively, it is slightly more powerful to analyze all three genetic models together (additive, dominant, and recessive), but only if the significance thresholds used to correct for analyzing multiple models are appropriately determined (such as by permutation). Finally, a commonly employed approach, testing the additive model alone, performs poorly for recessive causal alleles when the minor allele frequency is not close to 50%. Our observations were confirmed by analyzing an existing genetic association dataset in which we detect the effect of a KCNJ11 variant on insulinogenic index in unrelated non-diabetic individuals. PMID- 17352424 TI - Proteomic analysis of Burkholderia cepacia MBA4 in the degradation of monochloroacetate. AB - Burkholderia cepacia MBA4 is a bacterium that degrades 2-haloacids by removing the halogen and subsequent metabolism of the product for energy. In this study, 2 DE, MS/MS, and N-terminal amino acid sequencing were used to investigate the protein expression profiles of MBA4 grown in a 2-haloacid (monochloroacetate, MCA) and in the corresponding metabolic product (glycolate). Glycolate was used as a control to eliminate the proteins induced by it. Five proteins were found to be up-regulated and five proteins were down-regulated in response to MCA. The differentially expressed proteins were examined, seven of them were identified by MS/MS and two of them were sequenced by Edman degradation. Our results definitely provide an insight for understanding the physiology of B. cepacia MBA4 in response to organohalide contaminated site. PMID- 17352425 TI - Proteomic characterization of copper stress response in Cannabis sativa roots. AB - Cannabis sativa is an annual herb with very high biomass and capability to absorb and accumulate heavy metals in roots and shoots; it is therefore a good candidate for phytoremediation of soils contaminated with metals. Copper is an essential micronutrient for all living organisms, it participates as an important redox component in cellular electron transport chains; but is extremely toxic to plants at high concentrations. The aim of this work was to investigate copper effects on the root proteome of C. sativa, whose genome is still unsequenced. Copper stress induced the suppression of two proteins, the down-regulation of seven proteins, while five proteins were up-regulated. The resulting differences in protein expression pattern were indicative of a plant adaptation to chronic stress and were directed to the reestablishment of the cellular and redox homeostasis. PMID- 17352426 TI - A comprehensive proteome map of the lipid-requiring nosocomial pathogen Corynebacterium jeikeium K411. AB - Corynebacterium jeikeium is a lipid-requiring pathogen that is considered as part of the normal microflora of the human skin and associated with severe nosocomial infections. Systematic reference maps of the cytoplasmic, cell surface associated, and extracellular proteome fractions of the clinical isolate C. jeikeium K411 were examined by 2-DE coupled with MALDI-TOF MS. A sum total of 555 protein spots were identified by PMF, corresponding to 358 different proteins that were classified into functional categories and integrated into metabolic pathways. The majority of the proteins were linked to housekeeping functions in energy production and translation and to physiological processes in amino acid, carbohydrate, nucleotide, and lipid metabolism. A complete enzymatic machinery necessary to utilize exogenous fatty acids by beta-oxidation was detected in the cytoplasmic proteome fraction. In addition, several predicted virulence factors of C. jeikeium K411 were identified in the cell surface-associated and extracellular subproteome, including the cell surface proteins SurA and SurB, the surface-anchored pilus subunits SapA and SapB, the surface-anchored collagen adhesin CbpA, the cholesterol esterase Che, and the acid phosphatase AcpA. PMID- 17352427 TI - Detection of transient protein-protein interactions by bimolecular fluorescence complementation: the Abl-SH3 case. AB - Protein-protein interactions are essential in most biological processes. Many proteomic approaches have succeeded in the identification of strong and obligatory interactions but the study of weak and transient protein-protein interactions is still a challenge. The aim of the present study was to test the ability of bimolecular fluorescence complementation to detect and discriminate in vivo weak intracellular protein interactions. As a test case, the interaction of the SH3 domain from the c-Abl tyrosine kinase with both natural and designed targets has been chosen. The reassociation of functional yellow fluorescent protein (YFP) from its fragments requires previous binding between the SH3 domain and its partners; but once this occurs, the complex is trapped, turning transient SH3 interactions into stable, easily detectable ones. The method is very sensitive and can be implemented for proteomic analysis of weak protein interactions using flow cytometry. The fluorescence emission is dependent on the strength of the interaction, in such a way that it can be used, at least qualitatively, to screen for best binding candidates among similar proline-rich peptides. In addition, it is illustrated how this method can be used to gain structural insights into particular c-Abl SH3 interactions. PMID- 17352428 TI - Fabrication of Au nanowires of uniform length and diameter using a monodisperse and rigid biomolecular template: collagen-like triple helix. PMID- 17352429 TI - Anomer-selective glycosidase inhibition by 2-N-alkylated 1-azafagomines. AB - Alkylation of 1-azafagomine at the 2-N position was achieved by reductive amination of 1-N-acetyl-3,4,6-tri-O-benzyl-1-azafagomine by using aldehydes, palladium hydroxide, and hydrogen in EtOAc/water/acetic acid followed by deprotection. The 2-N-butyl, hexyl, heptyl, nonyl, decyl, and 3-phenylpropyl derivatives were made in this manner, and were tested for inhibition of alpha glucosidase from yeast, and of beta-glucosidase from almonds. The new compounds were stronger beta-glucosidase inhibitors than 1-azafagomine, but weaker alpha glucosidase inhibitors. PMID- 17352430 TI - Nondestructive mechanical release of ordered polymer microfiber arrays from porous templates. AB - The fabrication of one-dimensional (1D) nanostructures and microstructures inside the pores of porous templates is intensively investigated. The release of these structures is commonly accomplished by etching and destroying the templates. The 1D nanostructures and microstructures tend to condense because of the occurrence of capillary forces during drying of the specimens. It is shown that highly ordered arrays of polymer microfibers can be easily detached from silanized porous templates by mechanical lift-off. This procedure leaves the templates intact, thus allowing their recycling, and does not involve the use of solutions or solvents, thus circumventing condensation. Therefore, mechanical lift-off may enable the up-scaling of template-based approaches to the fabrication of highly ordered assemblies of 1D nanostructures and microstructures. PMID- 17352431 TI - Extremely high stability of glutathionate-protected Au25 clusters against core etching. PMID- 17352432 TI - Capillary kinetics of water in homogeneous, hydrophilic polymeric micro- to nanochannels. PMID- 17352433 TI - Direct electronic detection of prostate-specific antigen in serum. PMID- 17352434 TI - Intramolecular hydroamination/cyclisation of aminoallenes mediated by a neutral zirconocene catalyst: a computational mechanistic study. AB - The complete catalytic cycle for the intramolecular hydroamination/cyclisation (IHC) of 4,5-hexadien-1-ylamine (1) by a prototypical [ZrCp(2)Me(2)] precatalyst (2) has been scrutinized by employing a reliable DFT method. The present study conducted by means of a detailed computational characterisation of structural and energetic aspects of alternative pathways for all of the relevant elementary steps complements the mechanistic insights revealed from experimental results. The operative mechanism entails an initial transformation of precatalyst 2 into the thermodynamically prevalent, but dormant, bis(amido)-Zr compound in the presence of aminoallene 1. This complex undergoes a reversible, rate-determining alpha-elimination of 1 to form the imidoallene-Zr complex. The substrate-free form, which contains a chelating imidoallene functionality, is the catalytically active species and is rapidly transformed into azazirconacyclobutane intermediates through a [2+2] cycloaddition reaction. This highly facile process does not proceed regioselectively because the alternative pathways for the formation of five- and six-membered azacycles have comparable probabilities. Degradation of cyclobutane intermediates by following the most feasible pathway occurs through protonolysis of the metallacycle moiety and subsequent proton transfer from the Zr-NHR moiety onto the azacycle. The five-membered allylamine is generated through protonation at carbon atom C(6) followed by alpha-hydrogen elimination, whereas protonolysis of the cyclobutane moiety at the Zr-N bond followed by proton transfer onto carbon atom C(5) is the dominant route for the six-membered product. Of the two consecutive proton transfer steps, the second one determines the overall kinetics of the entire protonation sequence. This process is predicted to be substantially slower than the cycloaddition reaction. The factors that regulate the composition of the cycloamine products have been elucidated. PMID- 17352435 TI - Allele specific C-bulge probes with one unique fluorescent molecule discriminate the single nucleotide polymorphism in DNA. AB - A combination of an allele specific C-bulge probe and the fluorescent molecule N,N'-bis(3-aminopropyl)-2,7-diamino-1,8-naphthyridine (DANP) that binds specifically to the C-bulge provides a method for single nucleotide polymorphism (SNP) typing with only one fluorescent molecule without covalent modification of the DNA probe. The allele specific C-bulge probe contains one additional cytosine and produces a C-bulge directly flanking the SNP site upon hybridization to the target DNA. The C-bulge is a scaffold to recruit and retain DANP directly neighboring the SNP site. The DANP fluorescent probe was selectively modulated by the flanking matched and mismatched base pairs. The mutation type could be discriminated by the modulated fluorescent intensity with respect to the allele specific C-bulge probes used for the assay. PMID- 17352436 TI - Discussion on the formation and bonding in three [Ga8R10] compounds: the diversity in classical Ga-Ga bonds. AB - Herein we describe three Ga(8) compounds that feature gallium atoms in an oxidation state of 1.25 with normal valent 2e-2c bonding. Their structures and the influence of their ligands (phosphorus and nitrogen atoms directly bonded to the Ga(8) moieties) are discussed on the basis of DFT calculations, providing an insight into a probable mechanism for insertion reactions between GaX and GaX(3) species that lead to a reaction cascade via halides like Ga(2)X(4) and Ga(5)X(7) to Ga(8)X(10) and Ga(8)X(12) (2-), respectively. Finally, the Ga(8) cores of the three title compounds were compared with the topology of carbon atoms in C(8) alkanes. PMID- 17352438 TI - Na29Zn24Sn32: a zintl phase containing a novel type of {Sn14} enneahedra and heteroatomic {Zn8Sn4} icosahedra. PMID- 17352437 TI - Elucidating the mechanism of the asymmetric aza-Michael reaction. AB - The mechanism of the palladium-catalysed asymmetric aza-Michael addition of aniline to alpha,beta-unsaturated N-imide was examined from several aspects using a combination of techniques, including X-ray crystallography, mass spectrometry, NMR, UV/Vis spectroscopy, and kinetic studies. The binding of aniline to the dicationic palladium(II) metal centre was found to occur in two consecutive steps: The binding of the first aniline is fast and reversible, whereas the binding of the second aniline is slower and irreversible. This occurs in competition with the binding of the N-imide, which forms a planar six-membered chelate ring with the metal centre; coordinating through the 1,3-dicarbonyl moiety. Isotopic labelling revealed that the addition of N-H occurs in a highly stereoselective manner, allowing the synthesis of optically active beta(2)- and beta(2,3)-amino acid derivatives. The stereochemistry of the addition is postulated to be syn. In situ kinetic studies provided evidence for product inhibition. The binding of the N-imide to the catalyst was found to be the rate limiting step. Aniline was found to be an inhibitor of the pre-catalyst. The study culminated in the design of a new reaction protocol. By maintaining a low concentration of the aniline substrate during the course of the reaction, significant enhancement of yield and enantioselectivity can be achieved. PMID- 17352439 TI - Efficient bifunctional nanocatalysts by simple postgrafting of spatially isolated catalytic groups on mesoporous materials. PMID- 17352440 TI - Pentavalent arsenic can bind to biomolecules. PMID- 17352441 TI - Gamma-TaON: a metastable polymorph of tantalum oxynitride. PMID- 17352442 TI - In2Ge6O15(OH)2(H2dien): an open-framework indate germanate with one-dimensional 12-ring channels. PMID- 17352443 TI - Morita-Baylis-Hillman cyclizations of arene-ruthenium-functionalized acrylamides. PMID- 17352444 TI - Double insertion of isocyanides into dihydropyridines: direct access to substituted benzimidazolium salts. PMID- 17352445 TI - Intramolecular "hydroiminiumation" of alkenes: application to the synthesis of conjugate acids of cyclic alkyl amino carbenes (CAACs). PMID- 17352446 TI - A light-driven stereoselective biocatalytic oxidation. PMID- 17352447 TI - X-ray crystal structure of an alkene-pentacarbonyldicobalt-alkyne complex: isolation of a stable Magnus-type Pauson-Khand reaction intermediate. PMID- 17352448 TI - Asymmetric synthesis of antimicrotubule biaryl hybrids of allocolchicine and steganacin. AB - The asymmetric synthesis of novel axially chiral biaryl compounds 5 a-f containing a seven- or eight-membered heterocyclic medium ring is described. These molecules can be considered to be structural hybrids of allocolchicine- and steganacin-type natural products. The synthesis featured an atropo diastereoselective biaryl Suzuki coupling in which a benzylic stereocenter efficiently transferred its stereochemical information to the biaryl axis. The coupling conditions were optimized, and two biphenylphosphane ligands (DavePhos and S-Phos) were found to give the highest yields and diastereoselectivities. A three-element stereochemical model was proposed to explain the observed diastereoselectivities. In a second key step, the medium ring of the target molecules was formed by a stereoselective S(N)1-type cyclodehydration that probably involved a configurationally stable carbocationic intermediate, as supported by calculations. Alternatively, S(N)2-type cyclizations were employed on the same Suzuki coupling products to give the target molecules in a stereodivergent or stereoconvergent manner. These cyclization methods furnished the target hybrid analogues 5 a-f with ee values above 94 %. All analogues were evaluated as antimicrotubule agents and against a panel of cancer-cell lines using colchicine (1) and N-acetylcolchinol (3) as references. Promising activities were found for R,aR-configured compounds 5 a, b and 5 f; in particular, ethyl analogue 5 b showed a twofold antimicrotubule activity relative to colchicine. PMID- 17352449 TI - Translation of mutarotation into induced circular dichroism signals through helix inversion of host polymers. PMID- 17352450 TI - A review of the therapeutic agents used in the management of polycythaemia vera. AB - The acquired clonal disorder Polycythaemia Vera leads to increased erythropoiesis, myelopoiesis and megakaryopoeisis. These anomalies result in an increased incidence of thromboembolic events, transformation to acute leukaemia and myelofibrosis. Treatments which aim to reduce the event rate may increase anaemia but may also affect the rate of complications. This paper reviews the evidence for the treatments which have been used in the management of the disorders over a 50 plus year period. Assessment of this evidence and its limitations form the basis for the current suggested management plans. PMID- 17352451 TI - Successful ultrasound-guided laser treatment of fetal hydrops caused by pulmonary sequestration. AB - Microcystic or solid-looking fetal lung lesions associated with hydrops are associated with a high mortality rate. The most common of these lesions are microcystic congenital cystic adenomatoid malformations and pulmonary sequestrations (PS). Performing open fetal surgery by hysterotomy and lobectomy has, until now, been the only therapeutic option available following diagnosis of these lesions in the second trimester. Here we describe a new minimally invasive technique for the treatment of PS in the second trimester. Laser coagulation of the feeding systemic artery of the sequestration was performed under ultrasound guidance. The blood flow to the lung tumor was successfully arrested and hydrops reversed. The child was born at term and, at the time of writing, was alive and well at 2 years of age. Large PS with hydrops can be treated successfully by ultrasound-guided minimally invasive laser surgery. It is therefore important to utilize color Doppler ultrasound imaging for identification of a systemic feeding blood vessel in solid fetal lung tumors. Published by John Wiley & Sons, Ltd. PMID- 17352452 TI - Topology of the fibrinolytic system within the mural thrombus of human abdominal aortic aneurysms. AB - Development and progression of acquired abdominal aortic aneurysms (AAAs) involve proteolytic activity. In the present study, we investigate the distribution of fibrinolytic system components within mural thrombi of human AAAs. 20 mural thrombi and the remaining AAA walls were dissected. The luminal, intermediate and abluminal thrombus layers, and media and adventitia were separately incubated in cell culture medium. Conditioned media were then analysed for plasminogen activators (PAs), plasminogen activator inhibitor-1 (PAI-1), free-plasmin, plasmin alpha(2)-antiplasmin complexes (PAPs) and D-dimers release. In parallel, PA and PAI-1 mRNA expression analysis was performed by RT-PCR. The study was completed by immunohistochemical localization of these components in AAA, ex vivo functional imaging using (99m)Tc-aprotinin as a ligand and measurement of PAP and D-dimer plasma levels. All fibrinolytic system components were present in each aneurysmal layer. However, the mural thrombus was the main source of active serine-protease release. Interestingly, the luminal layer of the thrombus released greater amounts of PAPs and D-dimers. This paralleled the preferential immunolocalization of plasminogen and PAs, and the (99m)Tc-aprotinin scintigraphic signal observed in the luminal pole of the thrombus. In contrast, mRNA expression analysis showed an exclusive synthesis of tPA and PAI-1 within the wall, whereas uPA mRNA was also expressed within the thrombus. Taken together, these results suggest that the increased plasma concentrations of PAPs and D-dimers found in AAA patients are related to mural thrombus proteolytic activity, thus explaining their known link with AAA progression. Components of the fibrinolytic system could also represent a target for functional imaging of thrombus activities in AAA. PMID- 17352453 TI - Prenatal exposure to ultrasound waves: is there a risk? PMID- 17352454 TI - New triphosphate conjugates bearing reporter groups: labeling of DNA fragments for microarray analysis. AB - A simple and convenient method for incorporation of fluorescent or ligand groups into 3'-termini of DNA fragments is proposed. A set of triphosphoric acid monoesters bearing fluorescent groups or biotin attached to the triphosphate fragment through linkers of different lengths and structures was synthesized. All the compounds were substrates for calf thymus terminal deoxynucleotidyltransferase and were used for incorporation of marker groups into 3'-termini of DNA fragments. The compounds were successfully applied for DNA labeling during post-PCR target preparation for microarray analysis. PMID- 17352455 TI - Impact of bidentate chelators on lipophilicity, stability, and biodistribution characteristics of cationic 99mTc-nitrido complexes. AB - This report describes synthesis and evaluation of novel cationic 99mTc-nitrido complexes, [99mTcN(L)(PNP)](+) (L = ma, ema, tma, etma and mpo; PNP = PNP5, PNP6, and L6), as potential radiotracers for heart imaging. Cationic complexes [99mTcN(L)(PNP)](+) were prepared in two steps. For example, reaction of succinic dihydrazide with 99mTcO4(-) in the presence of excess stannous chloride and PDTA resulted in the [99mTcN(PDTA)n] intermediate, which then reacted Hmpo and PNP6 at 100 degrees C for 10-15 min to give [99mTcN(mpo)(PNP6)](+) in >90% yield. It was found that bidentate chelators have a significant impact on lipophilicity, solution stability, biodistribution, and metabolic stability of cationic 99mTc nitrido complexes. The fact that [99mTcN(ema)(PNP6)](+) decomposes rapidly in the presence of cysteine (1 mg/mL) while [99mTcN(etma)(PNP6)](+) and [99mTcN(mpo)(PNP6)](+) remain stable for >6 h under the same conditions strongly suggests that thione-S donors in bidentate chelators increase the solution stability of their cationic 99mTc-nitrido complexes. Biodistribution studies were performed on four cationic 99mTc-nitrido complexes in Sprague-Dawley rats. [99mTcN(etma)(PNP5)](+) is of particular interest due to its high initial heart uptake (1.81 +/- 0.35 %ID/g at 5 min postinjection), and long myocardial retention (1.99 +/- 0.47 %ID/g at 120 min postinjection). The heart/liver ratio of [99mTcN(etma)(PNP5)](+) (6.06 +/- 1.48) at 30 min postinjection is almost identical that of 99mTcN-DBODC5 (6.01 +/- 1.45), and is >2 times better than that of 99mTc-sestamibi (2.90 +/- 0.22). Results from metabolism studies show that [99mTcN(etma)(PNP5)](+) has no significant metabolism in the urine, but it does show significant metabolism in feces samples at 120 min postinjection. Planar imaging studies suggest that [99mTcN(etma)(PNP5)](+) might be able to give clinically useful images of the heart as early as 30 min postinjection. [99mTcN(etma)(PNP5)](+) is a very promising candidate for more preclinical evaluations in various animal models. PMID- 17352457 TI - Application of the general height equivalent to a theoretical plate equation to size exclusion chromatography. Study of the mass transfer of high-molecular-mass compounds in liquid chromatography. AB - The mass transfer of nonretained, high-molecular-weight polystyrene standards in a chromatographic column packed with 4-microm-diameter silica particles for SEC (average pore size 80 A) and eluted with tetrahydrofuran was investigated. The HETPs of nine polystyrene standards (MW 560, 760, 1780, 3680, 6400, 13,200, 19,300, 31,600, and 90,000) and of ethylbenzene were measured by the method of moments. These HETPs were accounted for by a general HETP equation previously derived for the mass transfer of low-molecular-weight compounds in RPLC (Gritti, F.; Guiochon, G. Anal. Chem. 2006, 78, 5329.). The best fit between the experimental and the theoretical HETPs allowed the estimation of the internal restricted diffusion coefficients of the polymers. The internal diffusion coefficients of the polystyrene standards were also measured, using the peak parking method. Both methods give comparable results and show that the restriction diffusion coefficient gammapKD decreases linearly with increasing logarithm of the polymer mass, from 0.56 for Log MW = 2.0 to 0 for Log MW = 4.8. Interestingly, the C term or limit slope of the high-velocity branch of the HETP curve passes through a maximum (highest mass-transfer resistance) for a polymer mass of 10 kDa. This maximum is well accounted for by the theoretical expression of the trans-particle mass-transfer contribution. PMID- 17352456 TI - Improvement of a recombinant anti-monkey anti-CD3 diphtheria toxin based immunotoxin by yeast display affinity maturation of the scFv. AB - Recently, a bivalent recombinant anti-human CD3 diphtheria toxin (DT) based immunotoxin derived from the scFv of UCHT1 antibody has been made that shows enhanced bioactivity and is free from the side effects of Fc receptor interaction. In this case, the diminution of CD3 binding due to the placement of the scFv domain at the C-terminus of the truncated DT in single scFv immunotoxins was compensated by adding an additional scFv domain. However, this strategy was less successful for constructing an anti-rhesus recombinant immunotoxin derived from the scFv of FN18 antibody due to poor binding of the anti-rhesus bivalent immunotoxin. We report here that, by increasing the FN18 scFv affinity through random mutagenesis and selection with a dye-labeled monkey CD3epsilongamma recombinant heterodimer, we greatly improved the bioactivity of FN18 derived immunotoxin. The best mutant, C207, contained nine mutations, two of which were located in CDRs that changed the charge from negative to positive. Binding affinity of the C207 scFv to the monkey T cell line HSC-F increased 9.8-fold. The potency of the C207 bivalent immunotoxin assayed by inhibition of protein synthesis increased by 238-fold. PMID- 17352458 TI - Conformational equilibration time of unfolded protein chains and the folding speed limit. AB - The speed with which the conformers of unfolded protein chains interconvert is a fundamental question in the study of protein folding. Kinetic evidence is presented here for the time constant for interconversion of disparate unfolded chain conformations of a small globular protein, cytochrome c, in the presence of guanidine hydrochloride denaturant. The axial binding reactions of histidine and methionine residues with the Fe(II) heme cofactor were monitored with time resolved magnetic circular dichroism spectroscopy after photodissociation of the CO complexes of unfolded protein obtained from horse and tuna and from several histidine mutants of the horse protein. A kinetic model fitting both the reaction rate constants and spectra of the intermediates was used to obtain a quantitative estimate of the conformational diffusion time. The latter parameter was approximated as a first-order time constant for exchange between conformational subensembles presenting either a methionine or a histidine residue to the heme iron for facile binding. The mean diffusional time constant of the wild type and variants was 3 +/- 2 mus, close to the folding "speed limit". The implications of the relatively rapid conformational equilibration time observed are discussed in terms of the energy landscape and classical pathway time regimes of folding, for which the conformational diffusion time can be considered a pivot point. PMID- 17352459 TI - Loop dynamics and ligand binding kinetics in the reaction catalyzed by the Yersinia protein tyrosine phosphatase. AB - The Yersinia protein tyrosine phosphatase (YopH) contains a loop of ten amino acids (the WPD loop) that covers the entrance of the active site of the enzyme during substrate binding. In this work the substrate mimicking competitive inhibitor p-nitrocatechol sulfate (PNC) is used as a probe of the active site. The dynamics of the WPD loop was determined by subjecting an equilibrated system containing YopH, PNC, and YopH bound to PNC to a laser induced temperature jump, and subsequently following the change in equilibrium due to the perturbation. Using this methodology the dynamics associated with substrate binding in YopH have been determined. These results indicate that substrate binding is coupled to the WPD loop motion, and WPD loop dynamics occur in the sub-millisecond time scale. The significance of these dynamic results is interpreted in terms of the catalytic cycle of the enzyme. PMID- 17352460 TI - Self-organizing maps for identification of new inhibitors of P-glycoprotein. AB - Self-organizing maps were trained to separate high- and low-active propafenone type inhibitors of P-glycoprotein. The trained maps were subsequently used to identify highly active compounds in a virtual screen of the SPECS compound library. PMID- 17352461 TI - Structure-activity relationship study to understand the estrogen receptor dependent gene activation of aryl- and alkyl-substituted 1H-imidazoles. AB - A series of C5-substituted 1,2,4-triaryl-1H-imidazoles was synthesized. Their gene-activating properties were determined on estrogen receptor alpha positive MCF-7 breast cancer cells, stably transfected with the plasmid EREwtcluc (MCF-7 2a cells). The influence of 4-OH and 2-Cl substituents on the phenyl rings as well as the significance of a methyl, ethyl, or phenyl group at C5 on the estrogen receptor binding and the resulting gene activation in MCF-7-2a cells was studied. The alkyl and aryl groups at C5 of 1,2,4-tris(4-hydroxyphenyl)-1H imidazole 1 increased the transactivation, while chlorine atoms on the phenyl rings diminished this effect. 5-Ethyl-1,2,4-tris(4-hydroxyphenyl)-1H-imidazole 9 was identified as the most active compound. Its excellent transcriptional activity did not only depend on the C5 ethyl group, but also on the three hydroxyl groups of the phenyl rings. Compounds (11-14) with a reduced number of hydroxyl groups displayed distinctly lower gene activation. PMID- 17352462 TI - Discovery of diaryl imidazolidin-2-one derivatives, a novel class of muscarinic M3 selective antagonists (Part 1). AB - Pharmacophore-based structural identification, synthesis, and structure-activity relationships of a new class of muscarinic M3 receptor antagonists, the diaryl imidazolidin-2-one derivatives, are described. The versatility of the discovered scaffold allowed for several structural modifications that resulted in the discovery of two distinct classes of compounds, specifically a class of tertiary amine derivatives (potentially useful for the treatment of overactive bladder by oral administration) and a class of quaternary ammonium salt derivatives (potentially useful for the treatment of respiratory diseases by the inhalation route of administration). In this paper, we describe the synthesis and biological activity of tertiary amine derivatives. For these compounds, selectivity for the M3 receptor toward the M2 receptor was crucial, because the M2 receptor subtype is mainly responsible for adverse systemic side effects of currently marketed muscarinic antagonists. Compound 50 showed the highest selectivity versus M2 receptor, with binding affinity for M3 receptor Ki = 4.8 nM and for M2 receptor Ki = 1141 nM. Functional in vitro studies on selected compounds confirmed the antagonist activity toward the M3 receptor and functional selectivity toward the M2 receptor. PMID- 17352463 TI - Discovery of diaryl imidazolidin-2-one derivatives, a novel class of muscarinic M3 selective antagonists (Part 2). AB - Synthesis and biological activity of a novel class of quaternary ammonium salt muscarinic M3 receptor antagonists, showing high selectivity versus the M2 receptor, are described. Selected compounds exhibited potent anticholinergic properties, in isolated guinea-pig trachea, and good functional selectivity for trachea over atria. In vivo, the same compounds potently inhibited acetylcholine induced bronchoconstriction after intratracheal administration in the guinea pig. PMID- 17352464 TI - Structure-based design, synthesis, and biological evaluation of potent and selective macrocyclic checkpoint kinase 1 inhibitors. AB - Based on the crystallographic analysis of a urea-checkpoint kinase 1 (Chk1) complex and molecular modeling, a class of macrocyclic Chk1 inhibitors were designed and their biological activities were evaluated. An efficient synthetic methodology for macrocyclic ureas was developed with Grubbs metathesis macrocyclization as the key step. The structure-activity relationship studies demonstrated that the macrocyclization retains full Chk1 inhibition activity and that the 4-position of the phenyl ring can tolerate a wide variety of substituents. These novel Chk1 inhibitors exhibit excellent selectivity over a panel of more than 70 kinases. Compounds 5b, 5c, 5f, 15, 16d, 17g, 17h, 17k, 18d, and 22 were identified as ideal Chk1 inhibitors, which showed little or no single agent activity but significantly potentiate the cytotoxicities of the DNA damaging antitumor agents doxorubicin and camptothecin. These novel Chk1 inhibitors abrogate the doxorubicin-induced G2 and camptothecin-induced S checkpoint arrests, confirming that their potent biological activities are mechanism-based through Chk1 inhibition. PMID- 17352465 TI - Probing the pharmacophore of ginkgolides as glycine receptor antagonists. AB - Ginkgolides are antagonists of the inhibitory ligand-gated ion channels for the neurotransmitters glycine and gamma-aminobutyric acid (GABA). In this study the ginkgolide structure was modified in order to investigate the minimum structural requirements for glycine receptor antagonism. The five native ginkgolides and a series of 29 ginkgolide derivatives were characterized at the three glycine receptor subtypes alpha1, alpha1beta, and alpha2, which revealed that only minor changes in the ginkgolide skeleton were allowed for maintaining glycine receptor antagonism. A pharmacophore model was generated and applied in a virtual screening of a compound database (300000 compounds), resulting in the identification of 31 hits. Twenty-seven of these hits were screened for biological activity, but none displayed antagonist activity at the glycine receptors. This strongly suggests the importance of other pharmacophore components in the binding of ginkgolides to glycine receptors, and we propose that the structural rigidity of the ginkgolide molecule may be crucial for its glycine receptor activity. PMID- 17352466 TI - Synthesis, structure, and magnetic properties of (A)[FeIII(oxalate)Cl2] (A = alkyl ammonium cations) with anionic 1D [FeIII(oxalate)Cl2]- chains. AB - The use of alkyl ammonium cations resulted in four compounds of (A)[FeIII(ox)Cl2] (A = Et3NH+ (1a, 1b), Me4N+ (2), and n-Bu4N+ (3); ox = oxalate), whose structures and magnetic properties were characterized. In all cases, the metal Fe(III) ions are six-coordinated by four oxygen atoms from two bischelating oxalate ligands and the two terminal Cl- ions in the cis position. Thus they form similar anionic 1D [FeIII(ox)Cl2]- chains. The chains are separated by alkyl ammonium cations in the lattice, and the cation size seems to control the interchain separation and packing patterns in the solid. A parallel arrangement of the [FeIII(ox)Cl2]- chains is observed for 1a, 2, and 3, while a crossed one is observed for 1b, which is a polymorph of 1a. Magnetic studies reveal the antiferromagnetic intrachain interactions in all compounds. The last three compounds, 1b, 2, and 3, show spin canting below 14.5, 9.5, and 3.8 K, respectively. The dipolar interaction over the interchain distance is proposed to be the result of 3D magnetic ordering in the materials. PMID- 17352467 TI - Synthesis and reactivity of Haloacetato derivatives of iron(II) including the crystal and the molecular structure of [Fe(CF3COOH)2(micro-CF3COO)2]n. AB - The syntheses of haloacetates of iron(II) and their reactivity are described. The compound Fe(CF3COO)2, 1, crystallizes from CF3COOH/(CF3CO)2O solution as the polynuclear [Fe(CF3COO)2(CF3COOH)2]n, 2, which contains bridging trifluoroacetates and monodentate trifluoroacetic acid groups. Fe(CF3COO)2(DMF)x, as obtained from Fe(CO)5 and CF3COOH/(CF3CO)2O in DMF, reacts with dioxygen at room temperature to give two micro3-oxo compounds, namely, [Fe3(micro3 O)(CF3COO)6(DMF)3], 3, a Fe(II)-Fe(III)-Fe(III) derivative, and [Fe4(micro3 O)2(micro2-CF3COO)6(CF3COO)2(DMF)4], 4, containing Fe(III) atoms only, which have been characterized by X-ray diffraction methods. Iron(II) chloro- and bromoacetates can be isolated by exchange reactions of iron(II) acetate with chloro- and bromo-substituted acetic acids in moderate to good yields. The stability of iron(II) haloacetates decreases on increasing the atomic weight and the number of halogens on the alpha-carbon atom. The species Fe(CX3COO)2 (X = Cl, 7; Br, 8), in THF solution, slowly convert into [Fe3(micro3-O)(CCl3COO)6(THF)3], 11, or [Fe3(micro3-O)(CBr3COO)6(THF)3][FeBr4], 10, respectively. Likewise, when iron(II) acetate (or trifluoroacetate) is left for several hours in the presence of a variety of haloacetic acids in THF, selective formation of different species, depending on the nature of the starting compound and of the acid employed, is observed. The formation of these products is the result of C-X bond activation (X = Cl, Br) and haloacetato decomposition, which occurs with concomitant oxidation at the metal centers. Carboxylic acid degradation species (CH2XCOOH, CX4, CX3H, CX2H2, X = Cl, Br) have been observed by GC-MS. PMID- 17352469 TI - Tuned polymer electrolyte membranes based on aromatic polyethers for fuel cell applications. AB - Poly(arylene ether sulfone)-based ionomers containing sulfofluorenyl groups have been synthesized for applications to polymer electrolyte membrane fuel cells (PEMFCs). In order to achieve high proton conductivity and chemical, mechanical, and dimensional stability, the molecular structure of the ionomers has been optimized. Tough, flexible, and transparent membranes were obtained from a series of modified ionomers containing methyl groups with the ion-exchange capacity (IEC) ranging from 1.32 to 3.26 meq/g. Isopropylidene tetramethylbiphenylene moieties were more effective than the methyl-substituted fluorenyl groups in giving a high-IEC ionomer membrane with substantial stability to hydrolysis and oxidation. Dimensional stability was significantly improved for the methyl substituted ionomer membranes compared to that of the non-methylated ones. This new ionomer membrane showed comparable proton conductivity to that of the perfluorinated ionomer membrane (Nafion 112) under a wide range of conditions (80 120 degrees C and 20-93% relative humidity (RH)). The highest proton conductivity of 0.3 S/cm was obtained at 80 degrees C and 93% RH. Although there is a decline of proton conductivity with time, after 10 000 h the proton conductivities were still at acceptable levels for fuel cell operation. The membranes retained their strength, flexibility, and high molecular weight after 10 000 h. Microscopic analyses revealed well-connected ionic clusters for the high-IEC membrane. A fuel cell operated using the polyether ionomer membrane showed better performance than that of Nafion at a low humidity of 20% RH and high temperature of 90 degrees C. Unlike the other hydrocarbon ionomers, the present membrane showed a lower resistance than expected from its conductivity, indicating superior water-holding capability at high temperature and low humidity. PMID- 17352468 TI - Triggering of the Bergman cyclization by photochemical ring contraction. Facile cycloaromatization of benzannulated cyclodeca-3,7-diene-1,5-diynes. PMID- 17352470 TI - Nephila clavipes spider dragline silk microstructure studied by scanning transmission X-ray microscopy. AB - Nephila clavipes dragline silk microstructure has been investigated by scanning transmission X-ray microscopy (STXM), a technique that allows quantitative mapping of the level of orientation of the peptide groups at high spatial resolution (<50 nm). Maps of the orientation parameter P2 have been derived for spider silk for the first time. Dragline silk presents a very fine microstructure in which small, highly oriented domains (average area of 1800 nm2, thus clearly bigger than individual beta-sheet crystallites) are dispersed in a dominant, moderately oriented matrix with several small unoriented domains. Our results also highlight the orientation of the noncrystalline fraction in silk, which has been underestimated in numerous structural models. No evidence of either a regular lamellar structure or any periodicity along the fiber was observed at this spatial resolution. The surface of fresh spider silk sections consists of a approximately 30-120 nm thick layer of highly oriented protein chains, which was found to vary with the reeling speed, where web building (0.5 cm/s) and lifeline (10 cm/s) spinning speeds were investigated. While the average level of orientation of the protein chains is unaffected by the spinning speed, STXM measurements clearly highlight microstructure differences. The slowpull fiber contains a larger fraction of highly oriented domains, while the protein chains are more homogeneously oriented in the fastpull fiber. In comparison, cocoon silk from the silkworm Bombyx mori presents a narrower orientation distribution. The strength-extensibility combination found in spider dragline silk is associated with its broad orientation distribution of highly interdigitated and unoriented domains. PMID- 17352472 TI - The gaseous enthalpy of formation of the ionic liquid 1-butyl-3-methylimidazolium dicyanamide from combustion calorimetry, vapor pressure measurements, and ab initio calculations. AB - Ionic liquids are attracting growing interest as alternatives to conventional molecular solvents. Experimental values of vapor pressure, enthalpy of vaporization, and enthalpy of formation of ionic liquids are the key thermodynamic quantities, which are required for the validation and development of the molecular modeling and ab initio methods toward this new class of solvents. In this work, the molar enthalpy of formation of the liquid 1-butyl-3 methylimidazolium dicyanamide, 206.2 +/- 2.5 kJ.mol-1, was measured by means of combustion calorimetry. The molar enthalpy of vaporization of 1-butyl-3 methylimidazolium dicyanamide, 157.2 +/- 1.1 kJ.mol-1, was obtained from the temperature dependence of the vapor pressure measured using the transpiration method. The latter method has been checked with measurements of 1-butyl-3 methylimidazolium bis(trifluoromethylsulfonyl) imide, where data are available from the effusion technique. The first experimental determination of the gaseous enthalpy of formation of the ionic liquid 1-butyl-3-methylimidazolium dicyanamide, 363.4 +/- 2.7 kJ.mol-1, from thermochemical measurements (combustion and transpiration) is presented. Ab initio calculations of the enthalpy of formation in the gaseous phase have been performed for 1-butyl-3 methylimidazolium dicyanamide using the G3MP2 theory. Excellent agreement with experimental results has been observed. The method developed opens a new way to obtain thermodynamic properties of ionic liquids which have not been available so far. PMID- 17352471 TI - An enzymatically activated fluorescence probe for targeted tumor imaging. AB - Beta-galactosidase is a widely used reporter enzyme, but although several substrates are available for in vitro detection, its application for in vivo optical imaging remains a challenge. To obtain a probe suitable for in vivo use, we modified our previously developed activatable fluorescence probe, TG-betaGal (J. Am. Chem. Soc. 2005, 127, 4888-4894), on the basis of photochemical and photophysical experiments. The new probe, AM-TG-betaGal, provides a dramatic fluorescence enhancement upon reaction with beta-galactosidase, and further hydrolysis of the ester moiety by ubiquitous intracellular esterases affords a hydrophilic product that is well retained within the cells without loss of fluorescence. We used a mouse tumor model to assess the practical utility of AM TG-betaGal, after confirming that tumors in the model could be labeled with an avidin-beta-galactosidase conjugate. This conjugate was administered to the mice in vivo, followed by AM-TG-betaGal, and subsequent ex vivo fluorescence imaging clearly visualized intraperitoneal tumors as small as 200 microm. This strategy has potential clinical application, for example, in video-assisted laparoscopic tumor resection. PMID- 17352473 TI - A structure-reactivity relationship for single walled carbon nanotubes reacting with 4-hydroxybenzene diazonium salt. AB - The first structure-reactivity relationship for electron-transfer reactions of single walled carbon nanotubes (SWNTs) has been derived and experimentally validated using 4-hydroxybenzene diazonium as a model electron acceptor. The model describes steady-state reaction data using an adsorption-controlled scheme, and electron transfer theories are used to explain the difference in reactivities between different nanotube chiralities. The formalism provides a mechanistic insight into electronically selective reactions. The influence of reagent concentration and external illumination (approximately 0.764 mW/cm2) on the reaction selectivity is described by the rate model, with quantitative descriptions of the changes in the UV-vis-nIR absorption spectra of nanotubes during reaction. Illumination was shown to decrease the selectivity of the reagent to metallic SWNTs over semiconducting SWNTs. We attribute this to the greater activity of the reagent in solution when exposed to light, resulting in greater extents of reaction for each SWNT and, hence, lower selectivity. PMID- 17352475 TI - Bimodal bond-length distributions in cobalt-doped CdSe, ZnSe, and Cd1-xZnxSe quantum dots. AB - Electronic absorption spectroscopy has been used to study changes in Co2+ ligand field parameters as a function of alloy composition in Co2+-doped Cd(1-x)Zn(x)Se nanocrystals. A shift in the energy of the 4T1(P) excited-state with alloy composition is observed. Analysis reveals that Co2+-Se2- bond lengths change relatively little as the host is varied continuously from CdSe to ZnSe, generating a large difference between microscopic and average cation-anion bond lengths in Co2+-doped CdSe nanocrystals but not in Co2+-doped ZnSe nanocrystals. The bimodal bond-length distributions observed here are shown to cause a diameter dependent enthalpic destabilization of doped semiconductor nanocrystals. PMID- 17352474 TI - Spectroscopic, computational, and kinetic studies of the mu4-sulfide-bridged tetranuclear CuZ cluster in N2O reductase: pH effect on the edge ligand and its contribution to reactivity. AB - A combination of spectroscopy and density functional theory (DFT) calculations has been used to evaluate the pH effect at the CuZ site in Pseudomonas nautica (Pn) nitrous oxide reductase (N2OR) and Achromobacter cycloclastes (Ac) N2OR and its relevance to catalysis. Absorption, magnetic circular dichroism, and electron paramagnetic resonance with sulfur K-edge X-ray absorption spectra of the enzymes at high and low pH show minor changes. However, resonance Raman (rR) spectroscopy of PnN2OR at high pH shows that the 415 cm-1 Cu-S vibration (observed at low pH) shifts to higher frequency, loses intensity, and obtains a 9 cm-1 18O shift, implying significant Cu-O character, demonstrating the presence of a OH- ligand at the CuICuIV edge. From DFT calculations, protonation of either the OH- to H2O or the mu4-S2- to mu4-SH- would produce large spectral changes which are not observed. Alternatively, DFT calculations including a lysine residue at an H bonding distance from the CuICuIV edge ligand show that the position of the OH- ligand depends on the protonation state of the lysine. This would change the coupling of the Cu-(OH) stretch with the Cu-S stretch, as observed in the rR spectrum. Thus, the observed pH effect (pKa approximately 9.2) likely reflects protonation equilibrium of the lysine residue, which would both raise E degrees and provide a proton for lowering the barrier for the N-O cleavage and for reduction of the [Cu4S(im)7OH]2+ to the fully reduced 4CuI active form for turnover. PMID- 17352476 TI - Instantaneous inclusion of a polynucleotide and hydrophobic guest molecules into a helical core of cationic beta-1,3-glucan polysaccharide. AB - We succeeded in the quantitative and selective introduction of an ammonium cationic group into the C6 position of Curdlan (CUR) by "Click Chemistry", and the obtained cationic Curdlan (CUR-N+) showed good solubility in water. ORD studies suggested that CUR-N+ adopts a single-stranded structure, different from a right-handed, triple-stranded helical structure of beta-1,3-glucan polysaccharides in water. It has been revealed that the polymeric complexes of CUR-N+ with polymeric guest molecules, such as polycytidylic acid (poly(C)), permethyldecasilane (PMDS), and single-walled carbon nanotubes (SWNTs), can be easily obtained by just mixing them in water with sonication. The characterization of the resultant CUR-N+-poly(C) complexes by UV-vis, CD spectroscopic measurements, and AFM and TEM observations revealed that they have stoichiometric, nanosized fibrous structures. From these experimental results as well as our precedent studies (e.g., refs 6 and 23), we propose that the complexation would be driven by the cooperative action of (1) the hydrogen bonding interaction between the OH group at the C2 position and hydrogen-bonding sites of the cytosine ring (ref 6d), (2) the electrostatic interaction between the ammonium cation and the phosphate anion (ref 23), as well as (3) the background hydrophobic interaction. In addition, the complexed polynucleotide chain showed a strong resistance against enzymatic hydrolysis. Likewise, the dispersion of PMDS and SWNTs in water by CUR-N+ and the fibrous structures of the complexes were confirmed by spectroscopic measurements as well as microscopic observations. These binding properties of CUR-N+, which can proceed spontaneously in water, clearly differ from those of schizophyllan (SPG), which inevitably require a denature-renature process corresponding to a conversion of a triple strand to single strands induced by DMSO or base for inclusion of polymeric guest molecules. PMID- 17352477 TI - On the photophysics of artificial blue-light photoreceptors: an ab initio study on a flavin-based dye dyad at the level of coupled-cluster response theory. AB - The photophysical behavior of a phenothiazine-phenyl-isoalloxazine dye dyad, a model system for blue-light photoreceptors functioning on the basis of photoinduced electron transfer, was investigated by employing a combination of time-dependent density functional and coupled-cluster response theory. A conical intersection between a "bright" locally excited and a "dark" charge-transfer state was found in the low-energy region of the corresponding potential energy surfaces. We propose that, for the solvated dyad, this conical intersection is responsible for the experimentally observed fast fluorescence quenching in that system. PMID- 17352478 TI - Role of aspartate-1 in Cu(II) binding to the amyloid-beta peptide of Alzheimer's disease. PMID- 17352479 TI - Spotlighting of cocaine by an autonomous aptamer-based machine. PMID- 17352480 TI - Palladium-catalyzed formal [4+2] cycloaddtion of o-xylylenes with olefins. PMID- 17352481 TI - Ionic liquids are useful contact angle probe fluids. PMID- 17352482 TI - Readily accessible, modular, and tuneable BINOL 3,3'-perfluoroalkylsulfones: highly efficient catalysts for enantioselective in-mediated imine allylation. PMID- 17352483 TI - Pd-catalyzed Kumada-Corriu cross-coupling reactions at low temperatures allow the use of Knochel-type Grignard reagents. PMID- 17352484 TI - Relative and absolute configuration of versipelostatin, a down-regulator of molecular chaperone GRP78 expression. AB - [structure: see text] Versipelostatin is the first compound which specifically inhibits the expression of GRP78 and the resultant robust cell death under stress conditions, in contrast to the weak cytotoxicity under normal conditions. Versipelostatin consists of a macrocyclic aglycone with an alpha-acyltetronic acid and three sugar moieties. The relative and absolute configuration of the aglycone moiety was established to be 4S, 5S, 6R, 9S, 10S, 13S, 16R, 18R, 19R, 20R, 24R, 27R, and 29S utilizing NMR techniques. PMID- 17352485 TI - Neoglycopeptide dendrimer libraries as a source of lectin binding ligands. AB - [structure: see text] A 15 625-membered peptide dendrimer combinatorial library was acylated with an alpha-C-fucosyl residue at its four N-termini and screened for binding to fucose-specific lectins. Dendrimer FD2 (Fuc-alpha-CH2CO-Lys-Pro Leu)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2 was identified as a potent ligand against Ulex europaeus lectin UEA-I (IC50 = 11 microM) and Pseudomonas aeruginosa lectin PA-IIL (IC50 = 0.14 microM). PMID- 17352486 TI - Domino metathesis of 3,6-dihydro-1,2-oxazine: access to isoxazolo[2,3-a]pyridin-7 ones. AB - [reaction: see text] Strained bicyclic 3,6-dihydro-1,2-oxazine is a reactive substrate in domino metathesis with an external alkene. This general transformation leads to isoxazolo[2,3-a]pyridin-7-one, a versatile scaffold combining chemical functions that could be selectively oxidized or reduced. The synthetic relevance of these domino metathesis products is demonstrated by a straightforward synthesis of a quinolizinone. PMID- 17352487 TI - Low-valent niobium-catalyzed reduction of alpha,alpha,alpha-trifluorotoluenes. AB - [reaction: see text] In the presence of 5 mol % of niobium(V) chloride, alpha,alpha,alpha-trifluorotoluene derivatives were reduced with lithium aluminum hydride to give toluene derivatives in good yields. Stepwise, partial reduction of bis(trifluoromethyl)benzene derivative was also demonstrated. PMID- 17352488 TI - Alpha-peptide/beta-peptoid chimeras. AB - [structure: see text] We describe the synthesis and characterization of the first generation of oligomers consisting of alternating repeats of alpha-amino acids and chiral N-alkyl-beta-alanine (beta-peptoid) residues. These chimeras are stable toward proteolysis, non-hemolytic, and possess antibacterial activity comparable to well-known antimicrobial agents. Moreover, the chimeras exhibit length-dependent, concentration-dependent, solvent-dependent, and ion-strength dependent ellipticity, indicating the presence of a secondary structure in solution. Thus, alpha-peptide/beta-peptoid oligomers represent a promising novel peptidomimetic backbone construct for biologically active ligands. PMID- 17352489 TI - Chromium-catalyzed arylmagnesiation of alkynes. AB - [reaction: see text] Arylmagnesiation of unfunctionalized alkynes in the presence of catalytic amounts of chromium(II) chloride and pivalic acid proceeds with high stereoselectivity. The alkenylmagnesium intermediate reacts with various electrophiles to afford the corresponding tetrasubstituted olefins in good yields. PMID- 17352490 TI - Alkylation of H-phosphinate esters under basic conditions. AB - An efficient and general procedure was developed for the direct alkylation of H phosphinate esters with LHMDS at low temperature. The simplicity of the reaction allows the use of various H-phosphinate esters and takes place with a wide range of electrophiles. The approach can be employed to access some GABA analogues or precursors to GABA analogues. The isolated yields are moderate to good. This is the first report of an alkylation with a secondary iodide or a primary chloride. PMID- 17352491 TI - Antimicrobial prenylated anthracene derivatives from the leaves of Harungana madagascariensis. AB - Three new prenylated anthranoids, harunmadagascarins C (1) and D (2) and kenganthranol D (3), together with three known compounds (4-6) were isolated from the leaves of Harungana madagascariensis. Their structures were assigned by spectroscopic methods and by comparison with literature data. In the three new natural products 1-3, one or two prenyl groups are incorporated in furan, pyran, or cyclohexane rings in four different modes of annulation. Compounds 2, 4, and 6 were strongly active against the Gram-positive Bacillus megaterium. PMID- 17352493 TI - A LuxP-FRET-based reporter for the detection and quantification of AI-2 bacterial quorum-sensing signal compounds. AB - Various bacterial species produce and monitor low-molecular weight signaling molecules that regulate specific sets of genes in a population density-dependent manner. This process is known as quorum sensing (QS). To date, the detection of QS signaling molecules from Gram-negative bacteria has relied primarily on bacterial reporter strains. These bioassays are subject to substantial interference by compounds that affect the growth and metabolism of the reporter strains. In addition, the sensitivity of reporter strains to QS signaling molecules is population density-dependent. Here, we describe the development of an in vitro assay system for the rapid detection and quantification of the furanosyl borate diester (BAI-2) subclass of autoinducer 2 (AI-2), QS molecules. The sensor is based on ligand binding-induced changes in fluorescence resonance energy transfer (FRET) between a cyan and yellow variant of GFP fused to the termini of the BAI-2 receptor, LuxP. Unexpectedly, the addition of synthetic BAI 2 to the purified biosensor induces a decrease in the level of FRET between the terminal fluorophores. Several lines of evidence, including mutation of the ligand binding sites, indicate that the observed FRET changes are BAI-2 dependent. The FRET-based BAI-2 biosensor responded to the addition of culture filtrates from wild-type Vibrio harveyi but exhibited no response to culture filtrates from V. harveyi mutants defective in BAI-2 synthesis. The sensitivity of the biosensor to BAI-2 (apparent Kd = 270 nM) was similar to that of BAI-2 bioassay systems. The limitations of microbial bioassay systems and the advantages and potential applications for the FRET-based BAI-2 biosensor are discussed. PMID- 17352494 TI - The rate enhancement produced by the ribosome: an improved model. AB - As a model for mechanistic comparison with peptidyl transfer within the ribosome, the reaction of aqueous glycinamide with N-formylphenylalanine trifluoroethyl ester (fPhe-TFE) represents an improvement over earlier model reactions involving Tris. The acidity of trifluoroethanol (pKa 12.4) resembles that of tRNA (12.98) more closely than do the acidities of model reactants described earlier, and the reactivity of the simple nucleophile glycinamide is free of potential complications that arise from alternative reaction pathways available to Tris. At 25 degrees C, the uncatalyzed reaction of glycinamide with fPhe-TFE proceeds with a second-order rate constant of 3 x 10(-5) M-1 s-1; DeltaH(++) = +7.8 kcal/mol; TDeltaS(++)= -15.7 kcal/mol. The ribosomal reaction of puromycin with fMet-tRNA proceeds 3 x 107-fold more rapidly, with a second-order rate constant (kcat/Km) of 1 x 10(3) M-1 s-1; DeltaH(++) = +16.0 kcal/mol; TDeltaS(++)= +2.0 kcal/mol. That rate enhancement, an order of magnitude larger than estimated earlier, is fully explained by the more favorable entropy of activation of the ribosomal reaction. Experiments involving ethylene glycol esters suggest that neighboring OH group effects are negligible in the presence of solvent water, which itself acts as a general base catalyst. In the desolvated interior of the ribosome, the vicinal 2'-OH group of aminoacyl-tRNA probably replaces water as a general base catalyst. But the catalytic effect of the ribosome itself is overwhelmingly entropic in origin, suggesting that the ribosome achieves its effect by physical desolvation and/or juxtaposition of the reactants in a manner conducive to peptidyl transfer. PMID- 17352495 TI - A pathogenic linked mutation in the catalytic core of human cystathionine beta synthase disrupts allosteric regulation and allows kinetic characterization of a full-length dimer. AB - Cystathionine beta-synthase catalyzes the condensation of serine and homocysteine to yield cystathionine and is the single most common locus of mutations associated with homocystinuria. In this study, we have examined the kinetic consequences of a pair of linked patient mutations, P78R/K102N, that are housed in the catalytic core of the protein and compared it to the effects of the corresponding single mutations. The P78R mutation affords purification of a mixture of higher order oligomers, P78R-I, which resembles the mixed quaternary state associated with wild-type enzyme. However, unlike wild-type enzyme, P78R-I converts over time to P78R-II, which exists predominantly as a full-length dimer. The specific activities of the K102N, P78R-I, and P78R-II mutants in the absence of AdoMet are approximately 3-, 9-, and 3-fold lower than of wild-type enzyme and are stimulated 2.9-, 2.5-, and 1.4-fold respectively by AdoMet. However, when linked, the specific activity of the resulting double mutant is comparable to that of wild-type enzyme but it is unresponsive to AdoMet, revealing that interactions between the two sites modulate the phenotype of the enzyme. Steady state kinetic analysis for the double mutant reveals a sigmoidal dependence on homocysteine that is not observed with wild-type enzyme, which is ascribed to the mutation at the K102 locus and indicates changes in subunit interactions. Hydrogen-deuterium mass spectrometric analysis reveals that, even in the absence of AdoMet, the double mutant is locked in an activated conformation that is observed for wild-type enzyme in the presence of AdoMet, providing a structural rationale for loss of this allosteric regulation. To our knowledge, this is the first example of mutations in the catalytic core of cystathionine beta-synthase that result in failure of AdoMet-dependent regulation. Furthermore, analysis of individual single mutations has permitted, for the first time, partial kinetic characterization of a full-length dimeric form of human cystathionine beta synthase. PMID- 17352496 TI - Thermodynamics of calmodulin trapping by Ca2+/calmodulin-dependent protein kinase II: subpicomolar Kd determined using competition titration calorimetry. AB - Calmodulin (CaM) trapping by Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a phenomenon whereby the affinity of CaM for CaMKII increases >1000-fold following CaMKII autophosphorylation. The molecular basis of this effect is not entirely understood. Binding of CaM to the phosphorylated and the unphosphorylated states of CaMKII is well mimicked by the interaction of CaM with two different length peptides taken from the CaM-binding region of CaMKII, peptides we refer to as the long and intermediate peptides. To better understand the conformational change accompanying CaM trapping, we have used isothermal titration calorimetry (ITC) to compare the binding thermodynamics of CaM to these peptides as well as to a shorter CaMKII-based peptide. Calorimetric analysis revealed that the enthalpy, rather than the entropy, distinguished binding of these three peptides. Furthermore, the heat capacity change was found to be similar for the long and intermediate peptides but smaller in magnitude for the short peptide. Direct titration of CaM with peptide provided the Kd value for the short peptide (Kd = 5.9 +/- 2.4 microM), but a novel, two-phased competitive binding strategy was necessary to ascertain the affinities of the intermediate (Kd = 0.17 +/- 0.06 nM) and long (Kd = 0.07 +/- 0.04 pM) peptides. To our knowledge, the Kd for the long peptide is the most potent measured to date using ITC. Together, the findings reported here support a model whereby the final conformational change accompanying CaM trapping buries little additional surface area but does involve formation of new hydrogen bonds and van der Waals contacts that contribute to formation of the high-affinity, CaM-trapped state. PMID- 17352497 TI - Mechanistic diversity in the RuBisCO superfamily: the "enolase" in the methionine salvage pathway in Geobacillus kaustophilus. AB - D-Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), the most abundant enzyme, is the paradigm member of the recently recognized mechanistically diverse RuBisCO superfamily. The RuBisCO reaction is initiated by abstraction of the proton from C3 of the d-ribulose 1,5-bisphosphate substrate by a carbamate oxygen of carboxylated Lys 201 (spinach enzyme). Heterofunctional homologues of RuBisCO found in species of Bacilli catalyze the tautomerization ("enolization") of 2,3 diketo-5-methylthiopentane 1-phosphate (DK-MTP 1-P) in the methionine salvage pathway in which 5-methylthio-d-ribose (MTR) derived from 5'-methylthioadenosine is converted to methionine [Ashida, H., Saito, Y., Kojima, C., Kobayashi, K., Ogasawara, N., and Yokota, A. (2003) A functional link between RuBisCO-like protein of Bacillus and photosynthetic RuBisCO, Science 302, 286-290]. The reaction catalyzed by this "enolase" is accomplished by abstraction of a proton from C1 of the DK-MTP 1-P substrate to form the tautomerized product, a conjugated enol. Because the RuBisCO- and "enolase"-catalyzed reactions differ in the regiochemistry of proton abstraction but are expected to share stabilization of an enolate anion intermediate by coordination to an active site Mg2+, we sought to establish structure-function relationships for the "enolase" reaction so that the structural basis for the functional diversity could be established. We determined the stereochemical course of the reaction catalyzed by the "enolases" from Bacillus subtilis and Geobacillus kaustophilus. Using stereospecifically deuterated samples of an alternate substrate derived from d ribose (5-OH group instead of the 5-methylthio group in MTR) as well as of the natural DK-MTP 1-P substrate, we determined that the "enolase"-catalyzed reaction involves abstraction of the 1-proS proton. We also determined the structure of the activated "enolase" from G. kaustophilus (carboxylated on Lys 173) liganded with Mg2+ and 2,3-diketohexane 1-phosphate, a stable alternate substrate. The stereospecificity of proton abstraction restricts the location of the general base to the N-terminal alpha+beta domain instead of the C-terminal (beta/alpha)8 barrel domain that contains the carboxylated Lys 173. Lys 98 in the N-terminal domain, conserved in all "enolases", is positioned to abstract the 1-proS proton. Consistent with this proposed function, the K98A mutant of the G. kaustophilus "enolase" is unable to catalyze the "enolase" reaction. Thus, we conclude that this functionally divergent member of the RuBisCO superfamily uses the same structural strategy as RuBisCO for stabilizing the enolate anion intermediate, i.e., coordination to an essential Mg2+, but the proton abstraction is catalyzed by a different general base. PMID- 17352499 TI - Selenium-based safety-catch linker: solid-phase synthesis of vinyl-substituted oxadiazoles and triazoles. AB - Vinyl-substituted oxadiazoles and triazoles were prepared through hydrazinolysis, acylation, cyclocondensation, and elimination of selenium resins. The polystyrene supported resins used here not only facilitate separation of products but also serve as a pro-vinyl safety-catch linker. PMID- 17352498 TI - 3'-Phosphoadenosine-5'-phosphosulfate reductase in complex with thioredoxin: a structural snapshot in the catalytic cycle. AB - The crystal structure of Escherichia coli 3'-phosphoadenosine-5'-phosphosulfate (PAPS) reductase in complex with E. coli thioredoxin 1 (Trx1) has been determined to 3.0 A resolution. The two proteins are covalently linked via a mixed disulfide that forms during nucleophilic attack of Trx's N-terminal cysteine on the Sgamma atom of the PAPS reductase S-sulfocysteine (E-Cys-Sgamma-SO3-), a central intermediate in the catalytic cycle. For the first time in a crystal structure, residues 235-244 in the PAPS reductase C-terminus are observed, depicting an array of interprotein salt bridges between Trx and the strictly conserved glutathione-like sequence, Glu238Cys239Gly240Leu241His242. The structure also reveals a Trx-binding surface adjacent to the active site cleft and regions of PAPS reductase associated with conformational change. Interaction at this site strategically positions Trx to bind the S-sulfated C-terminus and addresses the mechanism for requisite structural rearrangement of this domain. An apparent sulfite-binding pocket at the protein-protein interface explicitly orients the S sulfocysteine Sgamma atom for nucleophilic attack in a subsequent step. Taken together, the structure of PAPS reductase in complex with Trx highlights the large structural rearrangement required to accomplish sulfonucleotide reduction and suggests a role for Trx in catalysis beyond the paradigm of disulfide reduction. PMID- 17352500 TI - A QCM study of the immobilization of beta-galactosidase on polyelectrolyte surfaces: effect of the terminal polyion on enzymatic surface activity. AB - This work describes the immobilization of beta-galactosidase onto polyelectrolyte multilayer assemblies of the polyanion poly[1-[4-(3-carboxy-4 hydroxyphenylazo)benzenesulfonamido]-1,2-ethanediyl, sodium salt] (PAZO) and the polycation poly(ethylenimine) (PEI) constructed by electrostatic self-assembly (ESA). A single layer of beta-galactosidase was deposited over a precursor film comprising up to five bilayers of the PEI/PAZO polyelectrolyte pair. The enzyme was deposited on both the polycationic (PEI) and the polyanionic (PAZO) surfaces. Quartz crystal microbalance with dissipation monitoring (QCM-D), single wavelength ellipsometry, and UV-visible absorption spectroscopy revealed differences in both the amount of beta-galactosidase incorporated in each of the multilayer assemblies and the resulting enzyme packing density in the films. The enzymatic films were immersed in a reaction solution containing o-nitrophenyl beta-d-galactopyranoside (ONPG), and absorbance measurements were used to monitor the concentration of o-nitrophenyl (ONP), the product of the beta-galactosidase catalyzed by hydrolysis of ONPG. Although our data indicate that comparable amounts of beta-galactosidase are incorporated onto both surfaces, enzymatic activity is substantially inhibited when the beta-galactosidase is immobilized on the polyanionic surface compared to the enzyme on the polycationic surface. The difference in catalytic activities reflects the different abilities of the two polyelectrolytes to screen the protein's active site from the substrate environment. In both assemblies, the protein interpenetrated the PEI/PAZO multilayer, disrupting the J-aggregated state of the PAZO chromophores. This work demonstrates that the charge, conformation, and composition of underlying polyelectrolyte cushions have a significant effect on the structure and function of an immobilized protein within functional nanoassemblies. PMID- 17352501 TI - Interaction forces between talc and pitch probed by atomic force microscopy. AB - Colloidal wood resin components present in pulp are collectively called "pitch". The presence of pitch may cause severe problems due to deposits in and on the paper machine. There is thus a need for controlling pitch aggregation and adsorption. To be able to develop more efficient pitch control systems, one needs to develop the understanding of pitch-pitch interactions and of the interactions between pitch and other materials. With this general goal in mind, we present methods for preparing geometrically well-defined pitch particles attached to atomic force microscopy tips. This has enabled us to investigate the interactions between pitch and talc, an additive commonly used for pitch control. We have used model pitch particles consisting of one component only (abietic acid), a mixture of components (collophonium), and particles prepared from real pitch deposits. We show that the forces acting between pitch and talc are attractive and, once the initial approach is made, exert this attraction out to large distances of separation. We present evidence that the formation of bridging air bubbles or cavities is responsible for this interaction. PMID- 17352502 TI - Energy transfer in molecular layer-by-layer films of water-soluble perylene diimides. AB - Multilayer films of water-soluble anionic and cationic perylene diimide (PDI) moieties have been prepared using the molecular layer-by-layer method described in an earlier publication (Tang, T. J.; Qu, J. Q.; Mullen, K.; Webber, S. E. Langmuir 2006, 22, 26-28) and the fluorescence intensity compared with and without a base layer prepared using an anionic terrylene diimide dye (n-TDI), which serves as an energy-trapping layer for the PDI exciton. The fluorescence quenching data could be fit equally well to a modification of a model used by Kuhn to describe energy transfer from a J aggregate or a model developed by Kenkre and Wong to describe excitonic transfer. For both models, we obtain a characteristic energy-transfer distance on the order of 5.4 nm. Fluorescence quenching of the PDI via a single Forster energy-transfer step to the n-TDI layer is ruled out on the basis of the observed power-law dependence. We also consider a model in which the excitation is trapped at the outermost surface. This model provides a reasonable fit to the data only if the Kuhn relationship is used. PMID- 17352503 TI - Tunable quantum dots in bilayer graphene. AB - We demonstrate theoretically that quantum dots in bilayers of graphene can be realized. A position-dependent doping breaks the equivalence between the upper and lower layer and lifts the degeneracy of the positive and negative momentum states of the dot. Numerical results show the simultaneous presence of electron and hole confined states for certain doping profiles and a remarkable angular momentum dependence of the quantum dot spectrum, which is in sharp contrast with that for conventional semiconductor quantum dots. We predict that the optical spectrum will consist of a series of nonequidistant peaks. PMID- 17352504 TI - Polarizability of G4-DNA observed by electrostatic force microscopy measurements. AB - G4-DNA, a quadruple helical motif of stacked guanine tetrads, is stiffer and more resistant to surface forces than double-stranded DNA (dsDNA), yet it enables self assembly. Therefore, it is more likely to enable charge transport upon deposition on hard supports. We report clear evidence of polarizability of long G4-DNA molecules measured by electrostatic force microscopy, while coadsorbed dsDNA molecules on mica are electrically silent. This is another sign that G4-DNA is potentially better than dsDNA as a conducting molecular wire. PMID- 17352505 TI - A surface phase transition of supported gold nanoparticles. AB - A thermal phase transition has been resolved in gold nanoparticles supported on a surface. By use of asynchronous optical sampling with coupled femtosecond oscillators, the Lamb vibrational modes could be resolved as a function of annealing temperature. At a temperature of 104 degrees C the damping rate and phase changes abruptly, indicating a structural transition in the particle, which is explained as the onset of surface melting. PMID- 17352506 TI - Power generation by pressure-driven transport of ions in nanofluidic channels. AB - We report on the efficiency of electrical power generation in individual rectangular nanochannels by means of streaming currents, the pressure-driven transport of counterions in the electrical double layer. Our experimental study as a function of channel height and salt concentration reveals that the highest efficiency occurs when double layers overlap, which corresponds to nanoscale fluidic channels filled with aqueous solutions of low ionic strength. The highest efficiency of approximately 3% was found for a 75 nm high channel, the smallest channel measured. The data are well described by Poisson-Boltzmann theory with an additional electrical conductance of the Stern layer. PMID- 17352507 TI - Wavelength selective nanophotonic components utilizing channel plasmon polaritons. AB - We fabricate and investigate wavelength selective components utilizing channel plasmon polaritons (CPPs) and operate at telecom wavelengths: a waveguide-ring resonator-based add-drop multiplexer (WRR-ADM) and a compact (3.75-microm-long) Bragg grating filter (BGF). The CPP waveguides represent 0.5-microm-wide and 1.3 microm-deep V-grooves in gold, which are combined with a 5-microm-radius ring resonator (in the WRR-ADM) or 0.5-microm-long wells milled with the period of 0.75 microm across a groove (in the BGF). The CPP-based components are characterized in the wavelength range of 1425-1600 nm by use of near-field optical microscopy, exhibiting the wavelength selectivity of approximately 40 nm. PMID- 17352508 TI - Metal-molecule interface fluctuations. AB - We have created self-assembled circular chains of C60 laterally bound to a layer of Ag atoms as a model system for characterizing fluctuations at a metal-molecule interface. STM measurements show that the Ag and C60 sides of the interface fluctuate independently, with frequency-dependent amplitudes of magnitude 0.1 nm at approximately 1 Hz for the Ag edge and approximately 0.01 Hz for the C60 ring. The measured frequency spectra of the metal and molecule fluctuation amplitudes will contribute characteristic signatures to transport measurements involving such interfaces. PMID- 17352509 TI - Patterning polymeric structures with 2 nm resolution at 3 nm half pitch in ambient conditions. AB - The miniaturization limits of electronic and mechanical devices depend on the minimum pattern periodicity that is stable in ambient conditions. Here we demonstrate an atomic force microscopy lithography that enables the patterning of 2 nm organic structures with 6 nm periodicities in air. We also demonstrate that the lithography can be up-scaled for parallel patterning. The method is based on the formation of a nanoscale octane meniscus between a sharp conductive protrusion and a silicon (100) surface. The application of a high electrical field ( approximately 10 V/nm) produces the polymerization and cross-linking of the octane molecules within the meniscus followed by their deposition. The resulting pattern periodicities are very close to the ultimate theoretical limits achievable in air ( approximately 3 nm). The chemical composition of the patterns has been characterized by photoemission spectroscopy. PMID- 17352510 TI - Clostridium difficile-associated disease: changing epidemiology and implications for management. AB - Clostridium difficile-associated disease (CDAD) is increasingly being reported in many regions throughout the world. The reasons for this are unknown, are likely to be multifactorial, and are the subject of several current investigations. In addition to the upsurge in frequency of CDAD, an increased rate of relapse/recurrence, disease severity and refractoriness to traditional treatment have also been noted. Moreover, severe disease has been reported in non traditional hosts (e.g. younger age, seemingly healthy, non-institutionalised individuals residing in the community, and some without apparent antimicrobial exposure). A previously uncommon and more virulent strain of C. difficile has been reported at the centre of multiple transcontinental outbreaks. The appearance of this more virulent strain, in association with certain environmental and antimicrobial exposure factors, may be combining to create the 'perfect storm'. It is human nature to be reactive; however, the successful control of C. difficile will require healthcare systems (including administrators, and leadership within several departments such as environmental services, infection control, infectious diseases, gastroenterology, surgery, microbiology and nursing), clinicians, long-term care and rehabilitation facilities, and patients themselves to be proactive in a collaborative effort. Guidelines for the management of CDAD were last published over a decade ago, with the next iteration due in the fall (autumn) of 2007. Several newer therapies are under investigation but it is unclear whether they will be superior to current treatment options. PMID- 17352511 TI - ultra-long-acting beta2-adrenoceptor agonists: an emerging therapeutic option for asthma and COPD? AB - There has been a real interest recently in developing once-daily beta(2) adrenoceptor agonists (ultra-long-acting beta(2)-adrenoceptor agonists [ultra LABAs]) for treating asthma and chronic obstructive pulmonary disease (COPD) in an attempt to simplify their management, although an increasing amount of convincing data show an association of LABAs with a rise in asthma-related deaths and life-threatening experiences. This paper reviews the effects of different ultra-LABAs that are at varying stages of development. Arformoterol, carmoterol, indacaterol and GSK-159797 are ultra-LABAs that are likely to be introduced into the market before 2010. It is plausible that once-daily dose administration of an LABA will lead to increased convenience for patients, which may also lead to enhancement of adherence, and may have advantages leading to improved overall clinical outcomes in patients with asthma and COPD. PMID- 17352512 TI - The diagnosis and treatment of Raynaud's phenomenon: a practical approach. AB - Raynaud's phenomenon is a common disorder with vasospasm of the digital arteries causing pallor with cyanosis and/or rubor. It can be primary (idiopathic), where it is not associated with other diseases, or secondary to several diseases or conditions, including connective tissue diseases, such as scleroderma and systemic lupus erythematosus. Raynaud's is often mild enough to not require treatment; however, with secondary Raynaud's there is not only vasospasm but also fixed blood vessel defects so the ischaemia can be more severe. Complications can include digital ulcers and could, rarely, lead to amputation. Treatment is often non-pharmacological including avoiding cold and smoking cessation. Calcium channel antagonists, such as nifedipine, are often considered when treatment is needed; however, adverse effects of these drugs can include hypotension, vasodilatation, peripheral oedema and headaches. Other treatments have been studied in randomised, controlled trials including classes of drugs, such as angiotensin II inhibitors, selective serotonin reuptake inhibitors, phosphodiesterase-5 inhibitors (e.g. sildenafil), nitrates (topical or oral; the latter can be limited by adverse effects, such as flushing, headache and hypotension), and for more serious Raynaud's or its complications prostacyclin agonists may be used. There are two large studies that demonstrate that endothelin receptor blockade with bosentan can reduce the number of new digital ulcers in scleroderma patients. However, it does not affect the healing period. Thus, Raynaud's is common and often requires non-pharmacological treatment. When secondary Raynaud's is suspected, such as Raynaud's with an older age at onset or other features of connective tissue disease, then an appropriate history, physical examination and laboratory tests may be indicated to reach an appropriate diagnosis. There have been advances in pharmacological treatment, but some of the treatments are limited by adverse effects. PMID- 17352513 TI - Pharmacological Management of Peyronie's Disease. AB - Peyronie's disease is a localised, fibrosing condition of the penis that occurs in up to 9% of men. Although its aetiology has not been elucidated, Peyronie's disease probably results from the presence of a predisposing genetic susceptibility combined with an inciting event, most probably trauma. Following appropriate clinical evaluation, initial treatment consists of a trial of oral and/or intralesional pharmacotherapy. Oral therapies most commonly employed include para-aminobenzoate (Potaba) and tocopherol (vitamin E), with colchicine, tamoxifen, propoleum and acetyl-L-carnitine being used less frequently. Placebo controlled studies examining these agents have failed to show a consistent beneficial effect on Peyronie's disease, with the exception of para aminobenzoate, which may decrease plaque size and curvature, and acetyl-L carnitine, which may reduce erectile pain and inhibit disease progression. Intralesional injection therapy for Peyronie's disease is commonly used as a first-line therapy along with oral medications. The current standard of care involves injection with interferon-alpha-2a or -2b, verapamil or collagenase over 2-week intervals for a period of 5-6 months. Interferon-alpha-2b, in particular, has been documented in a large, multicentre, placebo-controlled study to be significantly more effective than placebo in decreasing penile curvature, plaque size, penile pain and plaque density. However, interferon treatment is also associated with significant adverse effects, including fever and other flu-like symptoms. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids and orgotein. Surgery is considered in patients with Peyronie's disease who have not responded to a trial of conservative medical therapy for 1 year and who are precluded from sexual intercourse. Procedures commonly performed include the Nesbit procedure (or variations of the Nesbit), penile plaque incision/excision with or without grafting, and implantation of a penile prosthesis. Further basic scientific research in Peyronie's disease is likely to identify additional targets for future pharmacotherapy. PMID- 17352514 TI - Premature ejaculation: definition and drug treatment. AB - Premature ejaculation (PE) is a frequent male sexual complaint that is mediated mainly by disturbances of serotonergic neurotransmission and certain serotonin (5 HT) receptors and, to a lesser extent, oxytocinergic neurotransmission in the CNS. The current Diagnostic Manual of Mental Disorders (fourth edition, revised text) [DSM-IV-TR] definition of PE has a low positive predictive value and is inadequate for clinical, epidemiological and drug treatment research. Categorisation of PE into four well defined syndromes has recently been proposed for the pending DSM (fifth edition) definition of PE. Over the last decade, an increasing number of studies of drug treatment of PE have been published. A meta analysis of those studies, conducted in accordance with current standards of evidence-based medicine, demonstrated similar efficacies for daily treatment with the serotonergic antidepressants paroxetine hemihydrate, clomipramine, sertraline and fluoxetine, with paroxetine (hydrochloride) hemihydrate exerting the strongest effect on ejaculation. On the basis of fundamental insights into serotonergic neurotransmission, it has been suggested that on-demand selective serotonin reuptake inhibitor (SSRI) treatment will not lead to similarly impressive delays in ejaculation as has been observed with daily SSRI treatment. Indeed, some on-demand studies with SSRIs and studies with the new SSRI dapoxetine have shown a weak ejaculation-delaying effect after 1-2 hours of drug intake. Apart from daily treatment with SSRIs, PE can be delayed by on-demand use of topical anaesthetics and tramadol. Treatment with phosphodiesterase type 5 inhibitors should not be prescribed to men with PE with normal erectile function, but may be used if PE is accompanied by erectile difficulties. There is no scientific support for treatment of PE with intracavernous injection of vasoactive drugs. Animal studies have shown that strong immediate ejaculation delay may be induced by administration of a combination of an SSRI with a serotonin 5-HT(1A) receptor antagonist. The combination of an SSRI and any other compound that immediately and potently raises serotonin neurotransmission and/or use of oxytocin receptor antagonists may form the basis for the development of new on-demand and/or daily drugs for the treatment of PE. PMID- 17352516 TI - Sitagliptin. AB - Sitagliptin, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. This increases active incretin and insulin levels, and decreases glucagon levels and post-glucose-load glucose excursion. In large, well designed phase III trials in patients with type 2 diabetes mellitus, sitagliptin 100 or 200mg once daily alone or in combination with other antihyperglycaemics was associated with significant improvements relative to placebo in overall glycaemic control and indices for insulin response and beta-cell function. Improvements from baseline in mean glycosylated haemoglobin (HbA(1c)) were significantly greater with sitagliptin monotherapy than with placebo in patients with type 2 diabetes. As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved HbA(1c) to a significantly greater extent than placebo when added to metformin or pioglitazone and was noninferior to glipizide when added to metformin. Sitagliptin was well tolerated when administered alone or in combination with other antihyperglycaemics, with an adverse event profile similar to that shown with placebo. The incidence of hypoglycaemia with sitagliptin was similar to that with placebo and, in combination with metformin, lower than that with glipizide. Sitagliptin had a generally neutral effect on bodyweight. PMID- 17352517 TI - Sitagliptin: a viewpoint by Mark S. Kipnes. PMID- 17352515 TI - Diabetic painful neuropathy: current and future treatment options. AB - Diabetic painful neuropathy (DPN) is one of the most common causes of neuropathic pain. The management of DPN consists of excluding other causes of painful peripheral neuropathy, maximising diabetic control and using medications to alleviate pain. The precise relationship between glycaemic control and the development and severity of DPN remains controversial. In this context, drugs such as aldose reductase inhibitors, ACE inhibitors, lipid-lowering agents and alpha-lipoic acid (thioctic acid) may have a useful role to play. There is also evidence that a successful pancreatic transplant may improve symptoms over time, but the mainstay of management continues to be symptomatic control of pain with drugs. Evidence from placebo-controlled studies has shown that opioids, antiepileptic and antidepressant drugs together with capsaicin are effective for alleviating DPN. Tramadol and oxycodone have been shown to be effective in studies of limited duration but their adverse effects, such as constipation and physical dependency, may limit their usefulness as a first-line treatment for DPN. Of the antidepressant drugs, the tricyclic antidepressants have been shown to be effective for alleviating DPN. These medications are widely used but their anticholinergic and sedative properties may not be well tolerated by patients. There is also good evidence that the serotonin-noradrenaline reuptake inhibitor antidepressant drugs venlafaxine and duloxetine are effective for treating DPN. However, venlafaxine may cause cardiac dysrhythmias, and patients using this medication require careful cardiac monitoring. Duloxetine appears to be less cardiotoxic and is licensed in the US and EU for alleviating DPN. The gabapentinoid group of drugs, gabapentin and pregabalin, appear to be the most evidence-based of the antiepileptic drugs for treating DPN. Large placebo controlled studies have been performed with both of these agents. For many patients, it is still unclear what advantages pregabalin has over gabapentin for DPN. Until better evidence emerges, the potential availability of less expensive generic formulations of gabapentin, together with greater experience with its use, favour gabapentin as the main antiepileptic drug for alleviating DPN. Topiramate, lamotrigine, sodium valproate and oxcarbazepine have been shown to be effective in smaller studies but do not have the same evidence base as the gabapentinoid group of drugs. Of the newer antiepileptic drugs, lacosamide appears to be the most promising for alleviating DPN. Capsaicin has the best evidence base of all the topical agents, but local anaesthetic patches may also have a useful therapeutic role. It is not possible to nominate a single drug as the first-line treatment for DPN and there is evidence that a low-dose combination of two or more drugs rather than a single agent may provide better symptomatic relief with fewer adverse effects. Further studies are necessary to clarify the best combination(s) of treatment for DPN. PMID- 17352518 TI - Sitagliptin: a viewpoint by Itamar Raz. PMID- 17352520 TI - Capecitabine in advanced gastric or oesophagogastric cancer: a viewpoint by Yoon Koo Kang. PMID- 17352519 TI - Capecitabine: in advanced gastric or oesophagogastric cancer. AB - The oral fluoropyrimidine capecitabine is metabolised preferentially in tumour tissue to the cytotoxic moiety fluorouracil. In a well designed phase III trial in patients with advanced gastric cancer, capecitabine plus cisplatin was noninferior to fluorouracil plus cisplatin in terms of progression-free survival (hazard ratio [HR] 0.81 [95% CI 0.63, 1.04]). In another similarly designed phase III trial in patients with oesophagogastric cancer (REAL 2), pooled capecitabine based regimens were noninferior to pooled fluorouracil-based regimens in terms of overall survival (HR 0.86 [95% CI 0.80, 0.99]). These data are supported by randomised and noncomparative phase II trials in treatment-naive or pretreated patients with advanced gastric cancer or oesophagogastric cancer receiving capecitabine either as monotherapy or in combination with other antitumour agents. Given the nature of chemotherapy, capecitabine-based regimens were generally well tolerated, with the nature of treatment-related adverse events occurring with capecitabine-based regimens being similar to those of fluorouracil based regimens. PMID- 17352521 TI - Capecitabine in advanced gastric or oesophagogastric cancer: a viewpoint by Sai Hong Ignatius Ou and Randall F. Holcombe. PMID- 17352523 TI - Drug therapy in dental practice: general principles. Part 2 - pharmacodynamic considerations. AB - The fundamental principles that govern drug therapy are often overlooked by the busy clinician. This disregard frequently results in the use of particular drugs and regimens that may be less ideal for the clinical situation being managed. By convention, these principles are categorized as pharmacokinetic and pharmacodynamic. Pharmacokinetic processes include drug absorption, distribution, biotransformation (metabolism), and elimination - essentially reflecting the influence of the body on the drug administered. These principles were addressed in the preceding issue of this journal. Pharmacodynamics deals with the actual mechanisms of action and effects a drug produces on the patient and is the topic for this continuing education article. PMID- 17352526 TI - An alternative approach to the monitoring of respiration by dynamic air-pressure sensor. AB - Monitoring and assessing of patient respiratory function during conscious sedation are important because many drugs used for conscious sedation produce respiratory depression and subsequent hypoventilation. The purpose of this study is to assess the value of a dynamic air-pressure sensor for respiratory monitoring of clothed patients. Eight clothed adult volunteers were reclined on a dental chair positioned horizontally. The air bag for measuring air-pressure signals corresponding to respiration was placed on the seat back of the dental chair in the central lumbar area of the subject. The subject breathed through a face mask with a respirometer attached for measuring expiratory tidal volume. The air-pressure signals corresponding to respiration were obtained and the time integration values for air pressure during each expiration (integral P(exp)) were calculated. The expiratory tidal volume (TV(exp)) was measured simultaneously by respirometer. The relationship between TV(exp) and integral P(exp) for each subject was assessed by a Pearson correlation coefficient. A strong correlation between TV(exp) and integral P(exp) was observed in all subjects. Measuring integral P(exp) by dynamic air-pressure sensor makes it possible to estimate respiratory volume breath by breath, and the respiratory pressure-time integral waveform was useful in visually monitoring the respiration pattern. We believe that in the future this device will be used to monitor respiratory physiology in clothed patients, contributing to safer sedative procedures. PMID- 17352522 TI - Clopidogrel: a review of its use in the prevention of thrombosis. AB - Clopidogrel (Plavix), Iscover) selectively and irreversibly inhibits adenosine diphosphate (ADP)-induced platelet aggregation. Long-term administration of clopidogrel was associated with a modest but statistically significant advantage over aspirin in reducing adverse cardiovascular outcomes in patients with established cardiovascular disease in the CAPRIE trial. In other large well designed multicentre trials, such as CURE, COMMIT and CLARITY-TIMI 28, the addition of clopidogrel to aspirin therapy improved outcomes in patients with acute coronary syndromes. However, some issues regarding the use of clopidogrel remain unresolved, such as the optimal loading dose in patients undergoing percutaneous coronary interventions (PCI) and the optimal treatment duration following drug-eluting intracoronary stent placement. Results of several large randomised trials, therefore, have established clopidogrel as an effective and well tolerated antiplatelet agent for the secondary prevention of ischaemic events in patients with various cardiovascular conditions, including those with ischaemic stroke or acute coronary syndromes. In addition, treatment guidelines from the US and Europe acknowledge the importance of clopidogrel in contemporary cardiovascular medicine. PMID- 17352528 TI - Anesthetic management of the trigeminocardiac reflex during mesiodens removal-a case report. AB - We describe a case in which reflection of a palatal flap for removal of a mesiodens is presented as the triggering factor for bradycardia caused by stimulation of the trigeminocardiac reflex. The management of the case, as well as the reflex arc, is discussed. PMID- 17352529 TI - Advances in understanding the actions of nitrous oxide. AB - Nitrous oxide (N(2)O) has been used for well over 150 years in clinical dentistry for its analgesic and anxiolytic properties. This small and simple inorganic chemical molecule has indisputable effects of analgesia, anxiolysis, and anesthesia that are of great clinical interest. Recent studies have helped to clarify the analgesic mechanisms of N(2)O, but the mechanisms involved in its anxiolytic and anesthetic actions remain less clear. Findings to date indicate that the analgesic effect of N(2)O is opioid in nature, and, like morphine, may involve a myriad of neuromodulators in the spinal cord. The anxiolytic effect of N(2)O, on the other hand, resembles that of benzodiazepines and may be initiated at selected subunits of the gamma-aminobutyric acid type A (GABA(A)) receptor. Similarly, the anesthetic effect of N(2)O may involve actions at GABA(A) receptors and possibly at N-methyl-D-aspartate receptors as well. This article reviews the latest information on the proposed modes of action for these clinical effects of N(2)O. PMID- 17352530 TI - Characterization and identification of microRNA core promoters in four model species. AB - MicroRNAs are short, noncoding RNAs that play important roles in post transcriptional gene regulation. Although many functions of microRNAs in plants and animals have been revealed in recent years, the transcriptional mechanism of microRNA genes is not well-understood. To elucidate the transcriptional regulation of microRNA genes, we study and characterize, in a genome scale, the promoters of intergenic microRNA genes in Caenorhabditis elegans, Homo sapiens, Arabidopsis thaliana, and Oryza sativa. We show that most known microRNA genes in these four species have the same type of promoters as protein-coding genes have. To further characterize the promoters of microRNA genes, we developed a novel promoter prediction method, called common query voting (CoVote), which is more effective than available promoter prediction methods. Using this new method, we identify putative core promoters of most known microRNA genes in the four model species. Moreover, we characterize the promoters of microRNA genes in these four species. We discover many significant, characteristic sequence motifs in these core promoters, several of which match or resemble the known cis-acting elements for transcription initiation. Among these motifs, some are conserved across different species while some are specific to microRNA genes of individual species. PMID- 17352531 TI - A look inside HIV resistance through retroviral protease interaction maps. AB - Retroviruses affect a large number of species, from fish and birds to mammals and humans, with global socioeconomic negative impacts. Here the authors report and experimentally validate a novel approach for the analysis of the molecular networks that are involved in the recognition of substrates by retroviral proteases. Using multivariate analysis of the sequence-based physiochemical descriptions of 61 retroviral proteases comprising wild-type proteases, natural mutants, and drug-resistant forms of proteases from nine different viral species in relation to their ability to cleave 299 substrates, the authors mapped the physicochemical properties and cross-dependencies of the amino acids of the proteases and their substrates, which revealed a complex molecular interaction network of substrate recognition and cleavage. The approach allowed a detailed analysis of the molecular-chemical mechanisms involved in substrate cleavage by retroviral proteases. PMID- 17352532 TI - Essential gene identification and drug target prioritization in Aspergillus fumigatus. AB - Aspergillus fumigatus is the most prevalent airborne filamentous fungal pathogen in humans, causing severe and often fatal invasive infections in immunocompromised patients. Currently available antifungal drugs to treat invasive aspergillosis have limited modes of action, and few are safe and effective. To identify and prioritize antifungal drug targets, we have developed a conditional promoter replacement (CPR) strategy using the nitrogen-regulated A. fumigatus NiiA promoter (pNiiA). The gene essentiality for 35 A. fumigatus genes was directly demonstrated by this pNiiA-CPR strategy from a set of 54 genes representing broad biological functions whose orthologs are confirmed to be essential for growth in Candida albicans and Saccharomyces cerevisiae. Extending this approach, we show that the ERG11 gene family (ERG11A and ERG11B) is essential in A. fumigatus despite neither member being essential individually. In addition, we demonstrate the pNiiA-CPR strategy is suitable for in vivo phenotypic analyses, as a number of conditional mutants, including an ERG11 double mutant (erg11BDelta, pNiiA-ERG11A), failed to establish a terminal infection in an immunocompromised mouse model of systemic aspergillosis. Collectively, the pNiiA-CPR strategy enables a rapid and reliable means to directly identify, phenotypically characterize, and facilitate target-based whole cell assays to screen A. fumigatus essential genes for cognate antifungal inhibitors. PMID- 17352533 TI - A specific primed immune response in Drosophila is dependent on phagocytes. AB - Drosophila melanogaster, like other invertebrates, relies solely on its innate immune response to fight invading microbes; by definition, innate immunity lacks adaptive characteristics. However, we show here that priming Drosophila with a sublethal dose of Streptococcus pneumoniae protects against an otherwise-lethal second challenge of S. pneumoniae. This protective effect exhibits coarse specificity for S. pneumoniae and persists for the life of the fly. Although not all microbial challenges induced this specific primed response, we find that a similar specific protection can be elicited by Beauveria bassiana, a natural fly pathogen. To characterize this primed response, we focused on S. pneumoniae induced protection. The mechanism underlying this protective effect requires phagocytes and the Toll pathway. However, activation of the Toll pathway is not sufficient for priming-induced protection. This work contradicts the paradigm that insect immune responses cannot adapt and will promote the search for similar responses overlooked in organisms with an adaptive immune response. PMID- 17352534 TI - Conversion of the BASE prion strain into the BSE strain: the origin of BSE? AB - Atypical neuropathological and molecular phenotypes of bovine spongiform encephalopathy (BSE) have recently been identified in different countries. One of these phenotypes, named bovine "amyloidotic" spongiform encephalopathy (BASE), differs from classical BSE for the occurrence of a distinct type of the disease associated prion protein (PrP), termed PrP(Sc), and the presence of PrP amyloid plaques. Here, we show that the agents responsible for BSE and BASE possess different biological properties upon transmission to transgenic mice expressing bovine PrP and inbred lines of nontransgenic mice. Strikingly, serial passages of the BASE strain to nontransgenic mice induced a neuropathological and molecular disease phenotype indistinguishable from that of BSE-infected mice. The existence of more than one agent associated with prion disease in cattle and the ability of the BASE strain to convert into the BSE strain may have important implications with respect to the origin of BSE and spongiform encephalopathies in other species, including humans. PMID- 17352535 TI - Outer surface protein B is critical for Borrelia burgdorferi adherence and survival within Ixodes ticks. AB - Survival of Borrelia burgdorferi in ticks and mammals is facilitated, at least in part, by the selective expression of lipoproteins. Outer surface protein (Osp) A participates in spirochete adherence to the tick gut. As ospB is expressed on a bicistronic operon with ospA, we have now investigated the role of OspB by generating an OspB-deficient B. burgdorferi and examining its phenotype throughout the spirochete life cycle. Similar to wild-type isolates, the OspB deficient B. burgdorferi were able to readily infect and persist in mice. OspB deficient B. burgdorferi were capable of migrating to the feeding ticks but had an impaired ability to adhere to the tick gut and survive within the vector. Furthermore, the OspB-deficient B. burgdorferi bound poorly to tick gut extracts. The complementation of the OspB-deficient spirochete in trans, with a wild-type copy of ospB gene, restored its ability to bind tick gut. Taken together, these data suggest that OspB has an important role within Ixodes scapularis and that B. burgdorferi relies upon multiple genes to efficiently persist in ticks. PMID- 17352536 TI - Live hot, die young: transmission distortion in recombination hotspots. AB - There is strong evidence that hotspots of meiotic recombination in humans are transient features of the genome. For example, hotspot locations are not shared between human and chimpanzee. Biased gene conversion in favor of alleles that locally disrupt hotspots is a possible explanation of the short lifespan of hotspots. We investigate the implications of such a bias on human hotspots and their evolution. Our results demonstrate that gene conversion bias is a sufficiently strong force to produce the observed lack of sharing of intense hotspots between species, although sharing may be much more common for weaker hotspots. We investigate models of how hotspots arise, and find that only models in which hotspot alleles do not initially experience drive are consistent with observations of rather hot hotspots in the human genome. Mutations acting against drive cannot successfully introduce such hotspots into the population, even if there is direct selection for higher recombination rates, such as to ensure correct segregation during meiosis. We explore the impact of hotspot alleles on patterns of haplotype variation, and show that such alleles mask their presence in population genetic data, making them difficult to detect. PMID- 17352538 TI - Preadolescents' and adolescents' online communication and their closeness to friends. AB - The 1st goal of this study was to investigate how online communication is related to the closeness of existing friendships. Drawing from a sample of 794 preadolescents and adolescents, the authors found that online communication was positively related to the closeness of friendships. However, this effect held only for respondents who primarily communicated online with existing friends and not for those who mainly talked with strangers. The 2nd goal was to refine 2 opposing hypotheses, the rich-get-richer and the social compensation hypotheses. Consistent with the rich-get-richer hypothesis, socially anxious respondents communicated online less often than did nonsocially anxious respondents. However, socially anxious respondents perceived the Internet as more valuable for intimate self-disclosure than did nonsocially anxious respondents, and this perception in turn led to more online communication. This result is consistent with the social compensation hypothesis. Online communication and closeness to friends increased with age. There was a curvilinear relationship between age and perceived value of the Internet for intimate self-disclosure, such that 15-year-olds were at the epitome of online self-disclosure. Girls were closer to friends and more socially anxious than were boys. PMID- 17352537 TI - Function-altering SNPs in the human multidrug transporter gene ABCB1 identified using a Saccharomyces-based assay. AB - The human ABCB1 (MDR1)-encoded multidrug transporter P-glycoprotein (P-gp) plays a major role in disposition and efficacy of a broad range of drugs including anticancer agents. ABCB1 polymorphisms could therefore determine interindividual variability in resistance to these drugs. To test this hypothesis we developed a Saccharomyces-based assay for evaluating the functional significance of ABCB1 polymorphisms. The P-gp reference and nine variants carrying amino-acid-altering single nucleotide polymorphisms (SNPs) were tested on medium containing daunorubicin, doxorubicin, valinomycin, or actinomycin D, revealing SNPs that increased (M89T, L662R, R669C, and S1141T) or decreased (W1108R) drug resistance. The R669C allele's highly elevated resistance was compromised when in combination with W1108R. Protein level or subcellular location of each variant did not account for the observed phenotypes. The relative resistance profile of the variants differed with drug substrates. This study established a robust new methodology for identification of function-altering polymorphisms in human multidrug transporter genes, identified polymorphisms affecting P-gp function, and provided a step toward genotype-determined dosing of chemotherapeutics. PMID- 17352539 TI - Cross-cultural differences in children's choices, categorizations, and evaluations of truths and lies. AB - This study examined cross-cultural differences and similarities in children's moral understanding of individual- or collective-oriented lies and truths. Seven , 9-, and 11-year-old Canadian and Chinese children were read stories about story characters facing moral dilemmas about whether to lie or tell the truth to help a group but harm an individual or vice versa. Participants chose to lie or to tell the truth as if they were the character (Experiments 1 and 2) and categorized and evaluated the story characters' truthful and untruthful statements (Experiments 3 and 4). Most children in both cultures labeled lies as lies and truths as truths. The major cultural differences lay in choices and moral evaluations. Chinese children chose lying to help a collective but harm an individual, and they rated it less negatively than lying with opposite consequences. Chinese children rated truth telling to help an individual but harm a group less positively than the alternative. Canadian children did the opposite. These findings suggest that cross-cultural differences in emphasis on groups versus individuals affect children's choices and moral judgments about truth and deception. PMID- 17352540 TI - Folkbiological reasoning from a cross-cultural developmental perspective: early essentialist notions are shaped by cultural beliefs. AB - In 2 experiments, the authors examined the evolution of folkbiological reasoning in children (4 to 10 years of age) and adults from 4 distinct communities (rural Native American, rural majority culture, and suburban and urban North American communities). Using an adoption paradigm, they examined participants' intuitions regarding the inheritance of properties and the mechanisms underlying the transmission of kindhood. Across all communities and ages, there was a strong biological component underlying reasoning about the inheritance of properties. There were also differences in children's intuitions about the mechanisms underlying kindhood: Native American children were more likely than their counterparts to consider blood as a candidate biological essence. This suggests that as children search to discover the underlying essence of a biological kind, they are guided by broad essentialist notions that are shaped by discourse within their community. PMID- 17352541 TI - How 14- and 18-month-olds know what others have experienced. AB - Fourteen- and 18-month-old infants observed an adult experiencing each of 2 objects (experienced objects) and then leaving the room; the infant then played with a 3rd object while the adult was gone (unexperienced object). The adult interacted with the 2 experienced objects in 1 of 3 ways: by (a) sharing them with the infant in an episode of joint engagement, (b) actively manipulating and inspecting them on his or her own as the infant watched (individual engagement), or (c) looking at them from a distance as the infant played with them (onlooking). As evidenced in a selection task, infants of both ages knew which objects had been experienced by the adult in the joint engagement condition, only the 18-month-olds knew this in the individual engagement condition, and infants at neither age knew this in the onlooking condition. These results suggest that infants are 1st able to determine what adults know (have experienced) on the basis of their direct, triadic engagements with them. PMID- 17352542 TI - Language and false belief: evidence for general, not specific, effects in cantonese-speaking preschoolers. AB - Two studies were conducted with Cantonese-speaking preschoolers examining J. de Villiers's (1995) hypothesis that syntactic complements play a unique role in the acquisition of false belief (FB). In Study 1, the authors found a positive correlation between FB and syntactic complements in 72 four- to six-year-old Cantonese-speaking preschoolers. Study 2 followed 72 three- to five-year-old Cantonese-speaking children who initially failed an FB screening task and were then tested on general language abilities, short-term memory, inhibition, nonverbal IQ, and on FB and complement tasks. Once age and initial FB understanding were controlled for in both multiple regression and hierarchical linear modeling analyses, complements no longer uniquely predicted FB. Instead, individual differences in general language abilities and short-term memory contributed to the variation in both complements and FB. PMID- 17352543 TI - Cumulative risk, maternal responsiveness, and allostatic load among young adolescents. AB - The purpose of this study was to examine the impact of cumulative risk exposure in concert with maternal responsiveness on physiological indicators of chronic stress in children and youth. Middle-school children exposed to greater accumulated psychosocial (e.g., family turmoil, poverty) and physical (e.g., crowding, substandard housing) risk factors manifested higher levels of allostatic load, a physiological marker of cumulative wear and tear on the body caused by the mobilization of multiple, physiological response systems. This effect was longitudinal, residualizing allostatic load 3-4 years earlier when the youth were in elementary school. This effect, however, occurred only among adolescents with mothers low in responsiveness. Cumulative risk was also associated with dynamic cardiovascular processes in response to an acute stressor (mental arithmetic). Higher risk was associated with muted reactivity and slower, less efficient recovery in blood pressure. These dynamic cardiovascular effects occurred irrespective of maternal responsiveness. PMID- 17352544 TI - Learning about tools in infancy. AB - These experiments explored the role of prior experience in 12- to 18-month-old infants' tool-directed actions. In Experiment 1, infants' use of a familiar tool (spoon) to accomplish a novel task (turning on lights inside a box) was examined. Infants tended to grasp the spoon by its handle even when doing so made solving the task impossible (the bowl did not fit through the hole in the box, but the handle did) and even though the experimenter demonstrated a bowl-grasp. In contrast, infants used a novel tool flexibly and grasped both sides equally often. In Experiment 2, infants received training using the novel tool for a particular function; 3 groups of infants were trained to use the tool differently. Later, infants' performance was facilitated on tasks that required infants to grasp the part of the tool they were trained to grasp. The results suggest that (a) infants' prior experiences with tools are important to understanding subsequent tool use, and (b) rather than learning about tool function (e.g., hammering), infants learn about which part of the tool is meant to be held, at least early in their exposure to a novel tool. PMID- 17352546 TI - Learning to map: strategy discovery and strategy change in young children. AB - A series of microgenetic experiments was conducted to examine the role of experience on 2.5- to 5-year-old children's discovery of spatial mapping strategies. With experience, 3- to 4-year-olds discovered a strategy for mapping corresponding locations that shared both featural and spatial similarities. When featural and spatial correspondences were placed in conflict, requiring children to negotiate both object-centered and location-centered mapping possibilities, 4- to 5-year-olds proved capable of discovering a novel mapping strategy, abandoning an ineffective strategy, and generalizing the acquired strategy across analogous tasks. Upon examining the mechanisms underlying developmental differences in strategy discovery and strategy change, the author observed that 3 key components contributed to the children's spatial mapping skills: encoding locations within each space, noticing a potential analogy between spaces, and detecting precise mapping correspondences. PMID- 17352545 TI - The developmental trajectories of attention focusing, attentional and behavioral persistence, and externalizing problems during school-age years. AB - The developmental trajectories of attention focusing (by parents' and teachers' reports) and attentional and behavioral persistence (observed during a laboratory task)--2 indexes of effortful control--and externalizing problems from ages 5 to 10 years were examined for 356 children combined from a pair of 3-wave (2 years apart) longitudinal studies. The authors identified clusters of children with distinct trajectories for these variables and examined the links between the effortful control trajectories and the externalizing problem trajectories. Although attention focusing remained relatively stable, attentional and behavioral persistence continued to show mean-level changes (especially among the children with lower levels of persistence). Children with high and stable trajectories of effortful control tended to exhibit low and stable trajectories of externalizing problems, whereas those with lower and/or less stable trajectories of effortful control showed more elevated and/or fluctuating trajectories of externalizing problems. PMID- 17352547 TI - Fitting objects into holes: on the development of spatial cognition skills. AB - The authors examined 14- to 26-month-old infants' understanding of the spatial relationships between objects and apertures in an object manipulation task. The task was to insert objects with various cross-sections (circular, square, rectangular, ellipsoid, and triangular) into fitting apertures. A successful solution required the infant to mentally rotate the object to be fit into the aperture and use that information to plan the action. The object was presented standing up in half of the trials; in the other half, it was lying down. The results showed that infants solved the problem consistently from age 22 months and that a successful solution was associated with appropriate preadjustments before the hand arrived with the block to the aperture. No sex differences were found. PMID- 17352549 TI - Under what conditions do young children have difficulty inhibiting manual actions? AB - Understanding how responses become prepotent is essential for understanding when inhibitory control is needed in everyday behavior. The authors investigated the conditions under which manual actions became prepotent in a go/no-go task. Children had to open boxes that contained stickers on go trials and leave shut boxes that were empty on no-go trials. In Experiment 1 (n = 40, mean age = 3.6 years), the authors obtained evidence consistent with this task requiring inhibitory control. Results of Experiment 2 (n = 40, mean age = 3.7 years) suggested that box opening was prepotent because (a) opening is the habitual action associated with boxes and (b) children planned to open boxes on go trials of the task. Experiment 3 (n = 96, mean age = 3.5 years) showed that even empty boxes elicited the same errors and that delaying responding reduced errors even though the delay occurred before the cue that indicated the correct response (contrary to a rule reflection account). Because the delay occurred after box presentation, performance was consistent with a transient activation account. Delay training might benefit children with weak inhibition. PMID- 17352550 TI - Parent-child relationships, partner relationships, and emotional adjustment: a birth-to-maturity prospective study. AB - This study examined whether detrimental childhood relationships with parents were related to partner relationship quality and emotional adjustment in adulthood. The authors tested a theoretical model in which (a) low-quality parent-child relationships were related to conflict and low-quality communication with parents in adolescence, (b) parent-adolescent conflict and low-quality communication were linked to low-quality partner relationships in young adulthood, and (c) low quality partner relationships in young adulthood were predictive of low-quality partner relationships as well as depression, anxiety, and dissatisfaction with life at midlife. Multi-informant data were used from 212 Swedish individuals who were followed from birth into adulthood. Results demonstrated that, as hypothesized, negative parent-child bonds were indirectly related to low-quality partner relationships and dissatisfaction with life in adulthood (but not anxiety and depression) through conflictual parent-adolescent communication and low quality partner relationships in young adulthood. PMID- 17352551 TI - Child negative emotionality and parenting from infancy to preschool: a meta analytic review. AB - This meta-analytic review (k = 62 studies; N = 7,613 mother-child dyads) shows that effect sizes for the association between child negative emotionality and parenting were generally small and were moderated by sample and measurement characteristics. The association between more child negative emotionality and less supportive parenting was relatively strong in lower socioeconomic status families, reversed in higher socioeconomic status families, and limited to studies with relatively high percentages of participants from ethnic minorities and studies using parent report to assess negative emotionality. Higher levels of child negative emotionality were associated with more restrictive control in samples with less than 75% 1st-born children, as well as in infants and preschoolers, and in studies using parent report or composite measures to assess both negative emotionality and restrictive parenting. Finally, more child negative emotionality was associated with less inductive control. PMID- 17352552 TI - Lexical exposure and word-form encoding in 1.5-year-olds. AB - In this study, 1.5-year-olds were taught a novel word. Some children were familiarized with the word's phonological form before learning the word's meaning. Fidelity of phonological encoding was tested in a picture-fixation task using correctly pronounced and mispronounced stimuli. Only children with additional exposure in familiarization showed reduced recognition performance given slight mispronunciations relative to correct pronunciations; children with fewer exposures did not. Mathematical modeling of vocabulary exposure indicated that children may hear thousands of words frequently enough for accurate encoding. The results provide evidence compatible with partial failure of phonological encoding at 19 months of age, demonstrate that this limitation in learning does not always hinder word recognition, and show the value of infants' word-form encoding in early lexical development. PMID- 17352553 TI - Memory plasticity across the life span: uncovering children's latent potential. AB - Memory plasticity, or the ability to improve one's memory performance through instruction and training, is known to decline during adulthood. However, direct comparisons among middle childhood, adulthood, and old age are lacking. The authors examined memory plasticity in an age-comparative multisession training study. One hundred and eight participants ages 9-10, 11-12, 20-25, and 65-78 years learned and practiced an imagery-based mnemonic technique to encode and retrieve words by location cues. Individuals of all ages were able to acquire and optimize use of the technique. Older adults and children showed similar baseline performance and improvement through mnemonic instruction. However, in line with tenets from life-span psychology (P. B. Baltes, 1987), children profited more from mnemonic practice and reached higher levels of final performance than did older adults. PMID- 17352555 TI - Social identities and intergroup bias in immigrant and nonimmigrant children. AB - Ethnic and American identity, as well as positivity and negativity toward multiple social groups, were assessed in 392 children attending 2nd or 4th grade in various New York City neighborhoods. Children from 5 ethnic groups were recruited, including White and Black Americans, as well as recent immigrants from China, the Dominican Republic, and the former Soviet Union. For ethnic minority children, greater positivity bias (evaluating one's ingroup more positively than outgroups) was predicted by immigrant status and ethnic identity, whereas negativity bias (evaluating outgroups more negatively than one's ingroup) was associated with increased age, immigrant status, and (among 4th graders only) ethnic identity. In addition, a more central American identity was associated with less intergroup bias among ethnic minority children. PMID- 17352554 TI - Multisensory exploration and object individuation in infancy. AB - Recent research indicates that by 4.5 months, infants use shape and size information as the basis for individuating objects but that it is not until 11.5 months that they use color information for this purpose. The present experiments investigated the extent to which infants' sensitivity to color information could be increased through select experiences. Five experiments were conducted with 10.5- and 9.5-month-olds. The results revealed that multimodal (visual and tactile), but not unimodal (visual only), exploration of the objects prior to the individuation task increased 10.5-month-olds' sensitivity to color differences. These results suggest that multisensory experience with objects facilitates infants' use of color information when individuating objects. In contrast, 9.5 month-olds did not benefit from the multisensory procedure; possible explanations for this finding are explored. Together, these results reveal how an everyday experience--combined visual and tactile exploration of objects--can promote infants' use of color information as the basis for individuating objects. More broadly, these results shed light on the nature of infants' object representations and the cognitive mechanisms that support infants' changing sensitivity to color differences. PMID- 17352556 TI - Intentional self-regulation and positive youth development in early adolescence: findings from the 4-h study of positive youth development. AB - In this research, the authors examined the development of intentional self regulation in early adolescence, which was operationalized through the use of a measure derived from the model of selection, optimization, and compensation (SOC). This model describes the individual's contributions to mutually influential relations between the person and his or her context. Through use of data from a longitudinal sample of 5th and 6th graders who were participating in the 4-H Study of Positive Youth Development (PYD), structural equation modeling procedure, reliability analyses, and assessments of convergent, divergent, and predictive validity suggested that a global, 9-item form of the SOC measure was a valid index of intentional self-regulation in early adolescence. Scores for this index of SOC were related to indicators of positive and negative development in predicted directions. The authors discuss the idea that self-regulation is a global process in early adolescence that contributes to PYD. PMID- 17352557 TI - Stage-environment fit during adolescence: trajectories of family relations and adolescent outcomes. AB - Within the framework of stage-environment fit theory, the authors examined the contribution of family relations to adolescent outcomes concurrently and longitudinally, as well as the moderating effects of gender and ethnicity in these associations. Data came from a longitudinal study of European American and African American families from a range of socioeconomic backgrounds. Results demonstrated that gender and ethnicity influenced both the level and rate of change in family relations and adolescent outcomes. Family relations contributed either concurrently or longitudinally to at least 1 of the adolescent outcomes. The effects of gender and ethnic moderation differed according to both the time frame and the outcome assessed. PMID- 17352558 TI - The process of emotion inference. AB - Three experiments investigated the process of inferring emotions from brief descriptions of typical eliciting situations, using response time methodology. The initial hypothesis was that emotion inferences are mediated by inferred cognitive appraisals of the eliciting event (concerning e.g., its valence or the responsible agent). This hypothesis was contradicted by the finding of Experiment 1 that emotion judgments are typically made faster than appraisal judgments. To explain this finding, it was hypothesized that emotion judgments are based on automatized (proceduralized) appraisal inferences. This hypothesis was tested in Experiments 2 and 3 using a judgment facilitation paradigm. The results supported the proceduralization hypothesis by demonstrating that appraisal judgments are facilitated by prior emotion judgments. PMID- 17352559 TI - Getting from situations to emotions: appraisal and other routes. AB - Comments on the original article by S. Siemer and R. Reisenzein regarding the process of emotion inference. When processing situational information, people can reach emotional conclusions without explicitly registering corresponding appraisals. Does this mean that appraisal cues must be guiding inference in less obvious ways? If one assumes that the emotional meaning of any situation depends on the protagonist's relation to what is happening, then emotion inference can never entirely bypass relational information. However, not all relational information is specifically appraisal-based. Further, actual emotion causation, like emotion inference, can involve explicit or implicit appraisals or even no appraisals at all. Indeed, humans do not first learn to associate emotions with situations by extracting appraisal information. PMID- 17352560 TI - Emotions and appraisals: can you have one without the other? AB - In his commentary on M. Siemer and R. Reisenzein (2007), B. Parkinson (2007) raised a number of important questions concerning the process of emotion inference and the scope of appraisal theories. Siemer and Reisenzein first examine the alternative explanations of their findings proposed by Parkinson and then look at the alternative "situated" view of emotions proposed by him. The main conclusion is that the issues raised by Parkinson can be dealt with by (suitable extensions of) appraisal theory. PMID- 17352561 TI - Emotion regulation and culture: are the social consequences of emotion suppression culture-specific? AB - Emotional suppression has been associated with generally negative social consequences (Butler et al., 2003; Gross & John, 2003). A cultural perspective suggests, however, that these consequences may be moderated by cultural values. We tested this hypothesis in a two-part study, and found that, for Americans holding Western-European values, habitual suppression was associated with self protective goals and negative emotion. In addition, experimentally elicited suppression resulted in reduced interpersonal responsiveness during face-to-face interaction, along with negative partner-perceptions and hostile behavior. These deleterious effects were reduced when individuals with more Asian values suppressed, and these reductions were mediated by cultural differences in the responsiveness of the suppressors. These findings suggest that many of suppression's negative social impacts may be moderated by cultural values. PMID- 17352562 TI - Inhibition of return to social signals of fear. AB - The present study examined whether inhibition of return (IOR) is modulated by the fear relevance of the cue. Experiment 1 found similar magnitude of IOR was produced by neutral and fear faces and luminance matched cues. To allow a more sensitive measure of endogenously directed attention, Experiment 2 removed a central reorienting cue and more precisely measured the time course of IOR. At stimulus onset asynchronies (SOAs) of 500, 1,000 and 1,500 ms, fear face and luminance matched cues resulted in similar IOR. These findings suggest that IOR is triggered by event onsets and disregards event value. Views of IOR as an adaptive "foraging facilitator," whereby attention is guided to promote optimal sampling of important environmental events, are discussed. PMID- 17352563 TI - Evidence for universality in phenomenological emotion response system coherence. AB - The authors reanalyzed data from Scherer and Wallbott's (Scherer, 1997b; Scherer & Wallbott, 1994) International Study of Emotion Antecedents and Reactions to examine how phenomenological reports of emotional experience, expression, and physiological sensations were related to each other within cultures and to determine if these relationships were moderated by cultural differences, which were operationally defined using Hofstede's (2001) typology. Multilevel random coefficient modeling analyses produced several findings of note. First, the vast majority of the variance in ratings was within countries (i.e., at the individual level); a much smaller proportion of the total variance was between countries. Second, there were negative relationships between country-level means and long- versus short-term orientation for numerous measures. Greater long-term orientation was associated with lowered emotional expressivity and fewer physiological sensations. Third, at the individual (within-culture) level, across the 7 emotions, there were consistent and reliable positive relationships among the response systems, indicating coherence among them. Fourth, such relationships were not moderated by cultural differences, as measured by the Hofstede dimensions. PMID- 17352564 TI - Task feedback effects on conflict monitoring and executive control: relationship to subclinical measures of depression. AB - Emerging evidence suggests that depression is associated with executive dysfunction, particularly after committing errors or receiving negative performance feedback. To test this hypothesis, 57 participants performed two executive tasks known to elicit errors (the Simon and Stroop Tasks) during positive or negative performance feedback. Participants with elevated depressive symptoms (Beck Depression Inventory scores >or= 13) were characterized by impaired posterror and postconflict performance adjustments, especially during emotionally negative task-related feedback. Additionally, for both tasks, depressive symptoms were inversely related to postconflict reaction time adjustments following negative, but not positive, feedback. These findings suggest that subclinical depression is associated with impairments in behavioral adjustments after internal (perceived failure) and external feedback about deficient task performance. PMID- 17352565 TI - Kindergarten children's emotion competence as a predictor of their academic competence in first grade. AB - This study examined the relation between emotion competence and academic competence and three potential mediators of this relation. In kindergarten, 193 children from elementary schools serving urban, minority, and low income students participated in an emotion competence assessment, and 142 of these children completed a follow-up assessment in first grade. The relation between teacher ratings of emotion regulation and academic competence was primarily indirect through the effect of emotion regulation on teacher ratings of attention. Peer acceptance and teacher closeness did not mediate the relations between emotion competence and academic competence. Results highlight the potential benefits of early emotion-centered prevention programs and the need to identify children with attention problems as early as possible to prevent academic difficulties. PMID- 17352566 TI - The role of attention and relatedness in emotionally enhanced memory. AB - Examining the positive and negative pictures separately revealed that emotionally enhanced memory (EEM) for positive pictures was mediated by attention, with no significant influence of emotional arousal, whereas the reverse was true of negative pictures. Consistent with this finding, in Experiment 2 EEM for negative pictures was found even when task emphasis was manipulated so that equivalent attention was allocated to negative and neutral pictures. The results show that attention and semantic relatedness contribute to EEM, with the extent varying with emotional valence. Negative emotion can influence memory independently of these 2 factors. PMID- 17352567 TI - Intoxication level and emotional response. AB - We used affective modulation of the eye-blink component of the startle reflex to examine effects of three levels of alcohol intoxication and a no-intoxication control on emotional responses to pleasant, neutral, and unpleasant pictures. Non problematic student drinkers (n=101; 48 female) were randomly assigned to intoxication groups. Normal inhibition of startle during exposure to pleasant pictures was intact across groups. In contrast, potentiation of startle during viewing of unpleasant pictures was evident in the no- and low-intoxication groups, compared to the intermediate- and high-intoxication groups, in which it was significantly reduced. This pattern suggests that a direct and selective anxiolytic effect of alcohol can occur at higher levels of intoxication without an analogous impact on response to emotionally positive stimuli at similar levels. PMID- 17352568 TI - Are facial expressions of emotion produced by categorical affect programs or dynamically driven by appraisal? AB - The different assumptions made by discrete and componential emotion theories about the nature of the facial expression of emotion and the underlying mechanisms are reviewed. Explicit and implicit predictions are derived from each model. It is argued that experimental expression-production paradigms rather than recognition studies are required to critically test these differential predictions. Data from a large-scale actor portrayal study are reported to demonstrate the utility of this approach. The frequencies with which 12 professional actors use major facial muscle actions individually and in combination to express 14 major emotions show little evidence for emotion specific prototypical affect programs. Rather, the results encourage empirical investigation of componential emotion model predictions of dynamic configurations of appraisal-driven adaptive facial actions. PMID- 17352569 TI - Toward a dialect theory: cultural differences in the expression and recognition of posed facial expressions. AB - Two studies provided direct support for a recently proposed dialect theory of communicating emotion, positing that expressive displays show cultural variations similar to linguistic dialects, thereby decreasing accurate recognition by out group members. In Study 1, 60 participants from Quebec and Gabon posed facial expressions. Dialects, in the form of activating different muscles for the same expressions, emerged most clearly for serenity, shame, and contempt and also for anger, sadness, surprise, and happiness, but not for fear, disgust, or embarrassment. In Study 2, Quebecois and Gabonese participants judged these stimuli and stimuli standardized to erase cultural dialects. As predicted, an in group advantage emerged for nonstandardized expressions only and most strongly for expressions with greater regional dialects, according to Study 1. PMID- 17352570 TI - Distinguishing between automaticity and attention in the processing of emotionally significant stimuli. AB - There is contradicting evidence as to whether irrelevant but significant emotional stimuli can be processed outside the focus of attention. In the current study, participants were asked to ignore emotional and neutral pictures while performing a competing task. In Experiment 1, orienting of attention to distracting pictures was manipulated via a peripheral cue. In Experiment 2, attentional load was varied, either leaving spare attention to process the distracting pictures or, alternatively, depleting attentional resources. Although all pictures were task irrelevant, negative pictures were found to interfere more with performance in comparison to neutral pictures. This finding suggests that processing of negative stimuli is automatic in the sense that it does not require execution of conscious monitoring. However, interference occurred only when sufficient attention was available for picture processing. Hence, processing of negative pictures was dependent on sufficient attentional resources. This suggests that processing of emotionally significant stimuli is automatic yet requires attention. PMID- 17352571 TI - Multimodal expression of emotion: affect programs or componential appraisal patterns? AB - In earlier work, the authors analyzed emotion portrayals by professional actors separately for facial expression, vocal expression, gestures, and body movements. In a secondary analysis of the combined data set for all these modalities, the authors now examine to what extent actors use prototypical multimodal configurations of expressive actions to portray different emotions, as predicted by basic emotion theories claiming that expressions are produced by fixed neuromotor affect programs. Although several coherent unimodal clusters are identified, the results show only 3 multimodal clusters: agitation, resignation, and joyful surprise, with only the latter being specific to a particular emotion. Finding variable expressions rather than prototypical patterns seems consistent with the notion that emotional expression is differentially driven by the results of sequential appraisal checks, as postulated by componential appraisal theories. PMID- 17352572 TI - Classifying chimpanzee facial expressions using muscle action. AB - The Chimpanzee Facial Action Coding System (ChimpFACS) is an objective, standardized observational tool for measuring facial movement in chimpanzees based on the well-known human Facial Action Coding System (FACS; P. Ekman & W. V. Friesen, 1978). This tool enables direct structural comparisons of facial expressions between humans and chimpanzees in terms of their common underlying musculature. Here the authors provide data on the first application of the ChimpFACS to validate existing categories of chimpanzee facial expressions using discriminant functions analyses. The ChimpFACS validated most existing expression categories (6 of 9) and, where the predicted group memberships were poor, the authors discuss potential problems with ChimpFACS and/or existing categorizations. The authors also report the prototypical movement configurations associated with these 6 expression categories. For all expressions, unique combinations of muscle movements were identified, and these are illustrated as peak intensity prototypical expression configurations. Finally, the authors suggest a potential homology between these prototypical chimpanzee expressions and human expressions based on structural similarities. These results contribute to our understanding of the evolution of emotional communication by suggesting several structural homologies between the facial expressions of chimpanzees and humans and facilitating future research. PMID- 17352573 TI - Common and distinct patterns of affective response in dimensions of anxiety and depression. AB - The authors examined the time course of affective responding associated with different affective dimensions--anxious apprehension, anxious arousal, and anhedonic depression--using an emotion-modulated startle paradigm. Participants high on 1 of these 3 dimensions and nonsymptomatic control participants viewed a series of affective pictures with acoustic startle probes presented before, during, and after the stimuli. All groups exhibited startle potentiation during unpleasant pictures and in anticipation of both pleasant and unpleasant pictures. Compared with control participants, symptomatic participants exhibited sustained potentiation following the offset of unpleasant stimuli and a lack of blink attenuation during and following pleasant stimuli. Common and unique patterns of affective responses in the 3 types of mood symptoms are discussed. PMID- 17352574 TI - When danger lurks in the background: attentional capture by animal fear-relevant distractors is specific and selectively enhanced by animal fear. AB - Across 2 experiments, a new experimental procedure was used to investigate attentional capture by animal fear-relevant stimuli. In Experiment 1 (N=34), unselected participants were slower to detect a neutral target animal in the presence of a spider than a cockroach distractor and in the presence of a snake than a large lizard distractor. This result confirms that phylogenetically fear relevant animals capture attention specifically and to a larger extent than do non-fear-relevant animals. In Experiment 2 (N=86), detection of a neutral target animal was slowed more in the presence of a feared fear-relevant distractor (e.g., a snake for snake-fearful participants) than in presence of a not-feared fear-relevant distractor (e.g., a spider for snake-fearful participants). These results indicate preferential attentional capture that is specific to phylogenetically fear-relevant stimuli and is selectively enhanced in individuals who fear these animals. PMID- 17352576 TI - The timing of appraisals. AB - The appraisal process consists of the subjective evaluation that occurs during an individual's encounter with significant events in the environment, determining the nature of the emotional reaction and experience. Placed in the context of appraisal theories of emotion-elicitation and differentiation, the aim of the present research was to test empirically the hypothesis that the intrinsic pleasantness evaluation occurs before the goal conduciveness evaluation. In two studies, intrinsically pleasant and unpleasant images were used to manipulate pleasantness, and a specific event in a Pacman-type videogame was used to manipulate goal conduciveness. Facial EMG was used to measure facial reactions to each evaluation. As predicted, facial reactions to the intrinsic pleasantness manipulation were faster than facial reactions to the goal conduciveness manipulation. These results provide good empirical support for the sequential nature of the appraisal process. PMID- 17352575 TI - Does processing of emotional stimuli predict symptomatic improvement and diagnostic recovery from major depression? AB - This study was designed to examine whether processing of emotional stimuli predicts both symptomatic improvement and recovery from depression. Participants diagnosed with Major Depressive Disorder (MDD) (N=63) completed information processing tasks to assess attention to and memory for sad, physically threatening, socially threatening, and happy stimuli. At a follow-up session an average of nine months later, participants were reassessed to determine diagnostic status and depression severity. None of the measure of attention or memory predicted diagnostic status at follow-up. Those depressed participants who remembered a higher proportion of positive words that they had endorsed as self descriptive exhibited greater symptomatic improvement. After controlling for memory of positive self-referential words, attentional measures did not predict symptomatic change. These results are consistent with a growing literature highlighting the importance of emotionally relevant memory processes for understanding the course of major depression. PMID- 17352577 TI - Sun and water: on a modulus-based measurement of happiness. AB - Most happiness researchers use semantic differential or Likert scales to assess happiness. Such conventionally used scales are susceptible to scale renorming (interpretation of scales differently in different contexts) and can produce a specious relativism effect (e.g., rating a low-income person happier than a high income person in situations where the low-income person is not happier). Building on related psychophysical measurements, the authors propose a simple, survey friendly, modulus-based scale of happiness and show that it is less susceptible to specious relativism than conventional rating scales but can still catch genuine relativism (e.g., rating a low-income person to be happier than a high income person in situations where the low-income person is indeed happier). PMID- 17352578 TI - Anger and time perception in children. AB - The present study investigated age-related variations in judgments of the duration of angry facial expressions compared with neutral facial expressions. Children aged 3, 5, and 8 years were tested on a temporal bisection task using angry and neutral female faces. Results revealed that, in all age groups, children judged the duration of angry faces to be longer than that of neutral faces. Findings are discussed in the framework of internal clock models and the adaptive function of emotion. PMID- 17352579 TI - Reflections by inner-city drug users on a Buddhist-based spirituality-focused therapy: a qualitative study. AB - A manual-guided, spirituality-focused intervention--spiritual self-schema (3-S) therapy--for the treatment of addiction and HIV-risk behavior was developed as part of a Stage I behavioral therapies development project. It is theoretically grounded in cognitive and Buddhist psychologies and may be suitable for individuals of diverse faiths. The therapy development process began with focus groups to assess addicted clients' perceived need for a spirituality-focused intervention. The therapy was then codified in manual format, and a controlled clinical trial was conducted. Here the authors report on inner-city, methadone maintained clients' personal experiences that were recorded in semistructured interviews following completion of the therapy. Findings from this qualitative study support the value of integrating spirituality-focused interventions into addiction treatment for the purpose of increasing motivation for drug abstinence and HIV prevention. PMID- 17352580 TI - Homophobia and conservative religion: toward a more nuanced understanding. AB - The failure of homophobia scales to consider the normative assumptions of religious communities may result in findings that are less useful in addressing this problem. In this study, 155 undergraduate students at a Christian university were surveyed, separately assessing attitudes toward celibate versus sexually active homosexual men and women. Results of multiple regression analyses found that participants who emphasized a person-behavior distinction (an accepted tenet of conservative religious ideology) held more negative attitudes toward lesbian women than those who were comparatively more accepting and did not emphasize such a distinction. However, participants who emphasized the person-behavior distinction held more positive attitudes toward gay men than those who were comparatively more rejecting and did not emphasize such a distinction. These relationships were significant even after accounting for variance attributable to general measures of religious commitment. Attempts to reduce homophobia within conservative religious communities may benefit from a more sensitive approach to their belief systems. PMID- 17352581 TI - Risk factors for first-time homelessness in low-income women. AB - Determinants of first-time homelessness were evaluated in Sacramento, California and Lehigh Valley, Pennsylvania. First-time homeless women had more cumulative risks for homelessness than low-income never-homeless women, even with the putative advantage of higher levels of education. Solutions to homelessness should address more than one dimension of risk. PMID- 17352582 TI - Siblings of adults with schizophrenia: expectations about future caregiving roles. AB - Sibling expectations to provide future instrumental or emotional support for a brother or sister with schizophrenia when parents became disabled or died were examined. Data came from a sample of 137 siblings participating in a longitudinal study of aging families of adults with schizophrenia. Early socialization experiences, the quality of the sibling relationship, and personal caregiver gains propel siblings toward a future caregiving role, whereas geographic distance and beliefs about the controllability of psychiatric symptoms reduce expectations of future involvement. PMID- 17352583 TI - Child adjustment and parenting in planned lesbian-parent families. AB - One hundred planned lesbian-parent families (i.e., two-mother families in which the child was born to the lesbian relationship) were compared with 100 heterosexual-parent families on child adjustment, parental characteristics, and child rearing. Questionnaires, observations, and a diary of activities were used to collect the data. The results show that especially lesbian social mothers (i.e., nonbiological mothers) differ from heterosexual fathers on parental characteristics (e.g., more parental justification and more satisfaction with the partner as coparent) and child rearing (e.g., more parental concern and less power assertion). Child adjustment is not associated with family type (lesbian parent families vs. heterosexual-parent families), but is predicted by power assertion, parental concern, and satisfaction with the partner as coparent. PMID- 17352584 TI - Help seeking among helping professionals: a role identity perspective. AB - Helping professionals, like the rest of the general population, have multiple identities (e.g., parent, community member), and many have prominent role identities as personal and professional caregivers. A recent instrument validation study illustrated that caregiver role identity is related to increased personal distress (e.g., depression, burnout), and this distress can negatively influence practitioners' professional work. This article builds on this research by expanding the conceptualization of role identity theory and extending its application to help seeking behaviors among 751 respondents in a representative sample of practicing social workers. Logistic regression analyses of data from this new measure suggest caregiver role identity may be an important risk factor for professionals needing to seek assistance for their own personal problems. PMID- 17352585 TI - Physical illness, functional limitations, and suicide risk: a population-based study. AB - The purpose of this study was to assess the independent association of physical illness and functional limitations with suicide mortality risk. The Cox proportional hazards model was used with data from the 1986-1994 National Health Interview Survey linked to the 1986-1997 National Death Index to analyze the effects of chronic physical illness and functional limitations on suicide deaths (ICD-9 E950-959). After controlling for potential confounders at baseline, functional limitations were shown to be a significant predictor of suicide. Also, psychiatric comorbidity increased the risk of completing suicide. Interestingly, chronic conditions alone were not predictive of suicide completion when functional limitation was added to the model. Implications for the clinical management of suicidal behavior among patients with chronic conditions are discussed. PMID- 17352586 TI - The longitudinal effect of intergenerational gap in acculturation on conflict and mental health in Southeast Asian American adolescents. AB - This longitudinal study examined the intergenerational gap in acculturation, subsequent conflict, and their mental health consequences in Southeast Asian American adolescents. It was hypothesized that perceived intergenerational discrepancy in acculturation during early adolescence would predict intergenerational conflict in late adolescence, which, in turn, would increase depressive symptomatology in late adolescence. Using data from the Children of Immigrants Longitudinal Study (A. Portes & R. G. Rumbaut, 2001; R. G. Rumbaut, 1994), 490 Southeast Asian American adolescents in 8th and 9th grades completed surveys and again 3 years later. The results supported the hypothesis and showed that intergenerational/intercultural conflict fully mediated the longitudinal effect of perceived intergenerational discrepancy in acculturation on depressive symptomatology. Recommendations for community-based interventions for both parents and youth are offered. PMID- 17352587 TI - Childhood institutional care and personality disorder traits in adulthood: findings from the British national surveys of psychiatric morbidity. AB - Long-term institutional care in childhood is linked with behavioral and emotional problems and can negatively affect personality development. This study tested the hypotheses that institutional care constitutes a risk factor for adult personality psychopathology and that conduct disorder acts as a mediator to the institutional care effects, based on 544 community individuals and 470 prisoners aged 18-64 years. Childhood institutional care was associated with elevated dependent, histrionic, and narcissistic traits in the community sample and with schizoid traits in prisoners. Initial findings of associations of institutional care with cluster B personality traits in the two populations disappeared after adjusting for conduct disorder symptoms. Identification and treatment of conduct/behavior problems in children before or during care may help to reduce the risk of developing certain personality disorder traits. PMID- 17352588 TI - Adolescent exposure to recurrent terrorism in Israel: posttraumatic distress and functional impairment. AB - This study examines the impact of exposure to ongoing terrorism on 695 Israeli high school students. Exposure was measured using a questionnaire developed for the security situation in Israel. Posttraumatic symptoms were measured using the UCLA PTSD Index for DSM-IV--Adolescent Version (N. Rodriguez, A. Steinberg, & R. S. Pynoos, 1999), functional impairment and somatic complaints were assessed using items derived from the Diagnostic Interview Schedule for Children (C. P. Lucas et al., 2001), and depression was measured with the Brief Beck Depression Inventory (A. T. Beck & R. W. Beck, 1972). According to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994), the prevalence of probable posttraumatic stress disorder was 7.6%. Girls reported greater severity of posttraumatic symptoms, whereas boys exhibited greater functional impairment in social and family domains. School-based screening appears to be an effective means of identifying adolescents who have been exposed to terror and are experiencing posttraumatic stress symptomatology and psychosocial impairment. PMID- 17352589 TI - Children's communication about distressing events: the role of emotional openness and psychological attributes of family members. AB - This study documents the importance of emotional openness to the recovery process in families following traumatic events. In this longitudinal study, relationships are examined between emotional openness and parents' psychological attributes, and mothers' and children's open disclosure of feelings. After September 11, 2001, 48 mothers and their 11-year-old children were interviewed about their reactions to the terrorist attacks. Measures included interview-based scores of children's and mothers' degree of openness, mothers' openness assessed during pregnancy and infancy, and parental depression and anxiety in close relationships. Emotional openness is a stable and reliably measured construct. Mothers' emotional openness was significantly related to earlier assessments of openness, indicators of their own and their spouse's emotional health, and their children's open expression of emotion about the terrorist attacks. PMID- 17352590 TI - Differential referral patterns to ethnic-specific and mainstream mental health programs for four Asian American groups. AB - This study examined the referral patterns of Chinese, Japanese, Filipino, and Korean Americans at ethnic-specific versus mainstream programs in a public mental health system. As predicted, social/ community-based services and family/friends to a lesser degree referred each Asian American group to ethnic-specific programs more than other referral sources (e.g., criminal justice and health services). Referrals by social/community-based programs to ethnic-specific versus mainstream programs were the most significant for Chinese Americans, followed by Japanese and Filipino Americans, and the least significant for Korean Americans. These findings suggest Asian American clients themselves and their social networks may view ethnic-specific programs as more culturally responsive than mainstream programs. PMID- 17352591 TI - Ever onward: the personal strivings of young adults coping with serious mental illness and the hopes of their parents. AB - This longitudinal study examined the personal strivings of young adults coping with mental illness, parents' hopes for their children, and attributes that adults and parents give to their strivings and hopes. Findings are based on separate interviews with a total of 60 young adults diagnosed with schizophrenia or bipolar disorder and their parents from 30 families. Adults and their parents generally expressed similar types of strivings and hopes and were persistent in strivings/hopes reported over a 1-year period. Adults were generally more optimistic than parents, anticipating more success in achieving their strivings with less difficulty and effort. Family agreement about strivings/hopes was significantly related to attribute ratings. Findings are discussed in the context of life span development and models of recovery. PMID- 17352592 TI - Modifiable risk and protective factors for depressive symptoms in low-income African American mothers. AB - Low-income African American mothers of young children experience high rates of depression, but many of the risk factors that have been identified provide little direction for intervention. The authors examined modifiable risk and protective factors for probable depression (Center for Epidemiological Studies Depression Scale >or= 23) in 824 African American mothers living in the 39 poorest census tracts in Detroit. Household food insufficiency and deteriorated housing significantly increased the odds of likely depression, whereas availability of a loan in a crisis, help with childcare, and transportation were protective. However, more frequent experiences of everyday discrimination greatly increased the odds of elevated depressive symptoms. These findings support the need for interventions that operate across individual and societal levels to address the fundamental causes of poor mental health. PMID- 17352593 TI - Racial differences in the characteristics of firearm suicide decedents in the United States. AB - Focusing on the reported growing use of firearms to complete suicide among African Americans, this article analyzes the 1993 National Mortality Followback Survey to examine the association of firearm suicide with race, education, geographic region, access to a firearm, depressive symptoms, and mental health service utilization on decedents aged 15 years and older. After controlling for demographic, socioeconomic, and clinical variables, the analysis indicates that African American men were twice as likely as White men to use a firearm to complete suicide. The findings suggest the importance for clinicians to screen for the presence of firearms in depressed African Americans and to reduce their access to firearms. In addition, clinicians, social workers, and public health professionals should consider racial differences in correlates of firearm suicide when designing prevention and intervention initiatives. PMID- 17352594 TI - Disparities in drug use and disorder: comparison of two American Indian reservation communities and a national sample. AB - Population-based samples provided estimates of drug use and disorder in two American Indian populations. Comparison to a national sample revealed tribal national, intertribal, and intratribal gender and age differences. Findings suggest that disparities in drug use and disorder are complex, characterized by important variations across diverse American Indian tribal cultures. PMID- 17352595 TI - Integrating behavioral health services for homeless mothers and children in primary care. AB - This article describes an innovative trauma-informed care management model in which mental health, substance abuse, and support services are integrated for homeless families in primary care. The rationale for service integration in a health care setting is discussed and the conceptual underpinnings of the model are elaborated, drawing from the literature and clinical experience. Service encounter data collected by each staff member over a 1-year period (N = 7,214 encounters) allow for description of program functions and provider roles and activities, an essential step in developing the fidelity indicators necessary for future program replication and rigorous testing in additional settings. The feasibility of implementing an integrated set of services for homeless families in primary care is demonstrated. Practice, training, and research implications are discussed. PMID- 17352596 TI - Evidence-based prevention practice in mental health: what is it and how do we get there? AB - A substantial number of children in the United States suffer from mental health problems. These children enter into adulthood at a disadvantage and often continue to experience mental health problems as adults. Historically, much less attention has been paid to prevention of mental health problems than to treatment and rehabilitative services. In recent years, however, great strides have been made in developing and evaluating prevention interventions in the area of mental health. Nevertheless, the study of prevention still lags behind clinical treatment research in identifying and disseminating effective programs and interventions. The following article draws on the work of numerous prevention scholars to develop a conceptual framework of evidence-based prevention practice in the area of mental health. Suggestions for how researchers, policy makers, and service providers can contribute to the development of evidence-based prevention practice in mental health are considered. PMID- 17352597 TI - Lesbian mothers with planned families: a comparative study of internalized homophobia and social support. AB - This study compared the perception of social support and the degree of internalized homophobia for two demographically similar groups: lesbians with planned families and lesbians who did not have children. Results found that lesbians with planned families perceived significantly less social support from friends overall, from gay men and lesbian friends specifically, and more support from their families-of-origin than lesbians who did not have children. Lesbians with planned families also reported significantly higher internalized homophobia specific to disclosure of sexual identification. The authors suggest that selective disclosure may be an adaptive response rather than a true measure of internalized homophobia. PMID- 17352598 TI - The central role of entitativity in stereotypes of social categories and task groups. AB - Research indicates that people's intuitive beliefs about groups are organized according to a group typology (B. Lickel, D. L. Hamilton, & S. J. Sherman, 2001). In Study 1, the authors compared and contrasted people's spontaneous cognitive representations of two group types, task groups and social categories. Analyses revealed significant differences as well as commonalities in people's beliefs about the group types. Notably, perceivers used more abstract, enduring language and contextually rich descriptors when characterizing social categories than when describing task groups. In Study 2, the authors investigated the differential roles of distinct group perception variables (entitativity, homogeneity, essence, role differentiation, and agency) as predictors of stereotyping for the different group types. Entitativity and all of the group perception variables significantly predicted stereotyping for both social categories and task groups. However, perceptions of entitativity mediated the association between the group perception variables and stereotypic judgments. These findings demonstrate that laypeople hold stereotype-like mental representations of group types other than social categories and that entitativity plays a crucial mediating role in stereotyping across different types of groups. PMID- 17352599 TI - The dilution model: how additional goals undermine the perceived instrumentality of a shared path. AB - Six experiments tested a dilution model of self-regulation, whereby increasing the number of goals (e.g., building muscles and losing weight) that a single means (e.g., exercising) can satisfy reduces the perception of its instrumentality with respect to each goal. The authors found that an increase in the number of simultaneous, salient goals that can be satisfied via a single means weakens the associative strength between that means and each individual goal, and as a result, individuals perceive the means as less effective for the attainment of each goal. Consequently, means that are connected to multiple (vs. single) goals are less likely to be chosen and pursued when only one of these goals is activated. PMID- 17352600 TI - The spyglass self: a model of vicarious self-perception. AB - Self-perception theory posits that people sometimes infer their own attributes by observing their freely chosen actions. The authors hypothesized that in addition, people sometimes infer their own attributes by observing the freely chosen actions of others with whom they feel a sense of merged identity--almost as if they had observed themselves performing the acts. Before observing an actor's behavior, participants were led to feel a sense of merged identity with the actor through perspective-taking instructions (Study 1) or through feedback indicating that their brainwave patterns overlapped substantially with those of the actor (Studies 2-4). As predicted, participants incorporated attributes relevant to an actor's behavior into their own self-concepts, but only when they were led to feel a sense of merged identity with the actor and only when the actor's behavior seemed freely chosen. These changes in relevant self-perceptions led participants to change their own behaviors accordingly. Implications of these vicarious self perception processes for conformity, perspective-taking, and the long-term development of the self-concept are discussed. PMID- 17352601 TI - Target and observer differences in the acceptance of questionable apologies. AB - Do people distinguish between sincere and insincere apologies? Because targets and observers face different constraints, we hypothesized that observers would differentiate between spontaneous and coerced apologies but that targets would not. In Studies 1 and 2 participants either received or observed a spontaneous apology, a coerced apology, or no apology, following a staged offense, and the predicted target-observer difference emerged. Studies 3-5 provided evidence in support of 3 mechanisms that contribute to this target-observer difference. Studies 3 and 4 indicate that this difference is due, in part, to a motivation to be seen positively by others and a motivation to feel good about oneself. Study 5 suggests that social scripts constrain the responses of targets more than those of observers. PMID- 17352602 TI - The role of need fulfillment in relationship functioning and well-being: a self determination theory perspective. AB - Self-determination theory posits 3 basic psychological needs: autonomy (feeling uncoerced in one's actions), competence (feeling capable), and relatedness (feeling connected to others). Optimal well-being results when these needs are satisfied, though this research has traditionally focused on individual well being outcomes (e.g., E. L. Deci & R. M. Ryan, 2000). Three studies examined the role of need fulfillment in relationship functioning and well-being. Study 1 found that fulfillment of each need individually predicted both individual and relationship well-being, with relatedness being the strongest unique predictor of relationship outcomes. Study 2 found that both partners' need fulfillment uniquely predicted one's own relationship functioning and well-being. Finally, in Study 3, the authors used a diary recording procedure and tested a model in which the association between need fulfillment and relationship quality was mediated by relationship motivation. Those who experienced greater need fulfillment enjoyed better postdisagreement relationship quality primarily because of their tendency to have more intrinsic or autonomous reasons for being in their relationship. PMID- 17352603 TI - Effects of social support visibility on adjustment to stress: experimental evidence. AB - Previous fieldwork has suggested that visible social support can entail an emotional cost and that a supportive act is most effective when it is accomplished either (a) outside of recipients' awareness or (b) within their awareness but with sufficient subtlety that they do not interpret it as support. To investigate the latter phenomenon, the authors conducted 3 experiments in which female participants were led to expect a stressful speech task and a confederate peer provided support in such a way that it was either visible or invisible (N=257). Invisible support (practical and emotional) reduced emotional reactivity relative to visible and no support. Visible support was either ineffective or it exacerbated reactivity. Explanatory analyses indicated that support was effective when it avoided communicating a sense of inefficacy to recipients. PMID- 17352604 TI - Realpolitik versus fair process: moderating effects of group identification on acceptance of political decisions. AB - Three studies examined the effects of perceived procedural justice and the favorability of a group-level outcome on the endorsement of a group-level decision and the evaluation of the authority responsible for the decision. Results showed that, contrary to findings usually seen with individual-level decisions, collective outcome favorability was more important than procedural justice in influencing the endorsement of the decision. Furthermore, increased identification with the group reduced the importance of procedural justice but accentuated the importance of collective outcome favorability. With regard to the evaluation of the authority, the results were similar to those obtained in individual-level decisions: Procedural fairness mattered more than collective outcome favorability. PMID- 17352605 TI - Rumination, emotion, and forgiveness: three longitudinal studies. AB - In 3 studies, the authors investigated whether within-persons increases in rumination about an interpersonal transgression were associated with within persons reductions in forgiveness. Results supported this hypothesis. The association of transient increases in rumination with transient reductions in forgiveness appeared to be mediated by anger, but not fear, toward the transgressor. The association of rumination and forgiveness was not confounded by daily fluctuations in positive affect and negative affect, and it was not moderated by trait levels of positive affectivity, negative affectivity, or perceived hurtfulness of the transgression. Cross-lagged associations of rumination and forgiveness in Study 3 more consistently supported the proposition that increased rumination precedes reductions in forgiveness than the proposition that increased forgiveness precedes reductions in rumination. PMID- 17352606 TI - The psychological structure of pride: a tale of two facets. AB - To provide support for the theoretical distinction between 2 facets of pride, authentic and hubristic (J. L. Tracy & R. W. Robins, 2004a), the authors conducted 7 studies. Studies 1-4 demonstrate that the 2 facets (a) emerge in analyses of the semantic meaning of pride-related words, the dispositional tendency to experience pride, and reports of actual pride experiences; (b) have divergent personality correlates and distinct antecedent causal attributions; and (c) do not simply reflect positively and negatively valenced, high- and low activation, or state versus trait forms of pride. In Studies 5-7, the authors develop and demonstrate the reliability and validity of brief, 7-item scales that can be used to assess the facets of pride in future research. PMID- 17352607 TI - Mental habits: metacognitive reflection on negative self-thinking. AB - In 8 studies, the authors investigated negative self-thinking as a mental habit. Mental content (negative self-thoughts) was distinguished from mental process (negative self-thinking habit). The negative self-thinking habit was assessed with a metacognitive instrument (Habit Index of Negative Thinking; HINT) measuring whether negative self-thoughts occur often, are unintended, are initiated without awareness, are difficult to control, and are self-descriptive. Controlling for negative cognitive content, the authors found that negative self thinking habit was distinct from rumination and mindfulness, predicted explicit as well as implicit low self-esteem (name letter effect), attenuated a positivity bias in the processing of self-relevant stimuli, and predicted anxiety and depressive symptoms 9 months later. The results support the assumption that metacognitive reflection on negative self-thinking as mental habit may play an important role in self-evaluative processes. PMID- 17352608 TI - The confirmability and disconfirmability of trait concepts revisited: does content matter? AB - M. Rothbart and B. Park (1986) demonstrated that, consistent with the common negativity bias, positive traits are difficult to confirm and easy to disconfirm, whereas the opposite is true for negative traits. This article extends their analysis by showing that trait (dis-)confirmability is moderated by trait content (warmth vs. competence). Study 1 identifies a trait sample representative of warmth and competence. Study 2 shows a strong negativity effect for warmth and a reduced (or absent) negativity effect for competence. Study 3 examines trait properties related to the behavioral range of the trait possessor and to the motivational goals of the perceiver as predictors of trait (dis-)confirmability. The theoretical and practical implications of the authors' findings are discussed, and avenues for future research are suggested. PMID- 17352609 TI - Origins of adolescents' ideal self: an intergenerational perspective. AB - The present longitudinal study traced the ideal self of 120 adolescents to the ideals that parents hold for themselves and for their children. Ideals were assessed using Q sorts for personality attributes and life goals. After permutation analysis was used to control for random similarity, moderate parent child ideal-self similarity was evident. Three intermediate transmission steps accounted for this intergenerational similarity: (a) transfer of parents' ideal self to ideals for their children, (b) children's perception, and (c) acceptance of these parental ideals. The last 2 processes related to parenting practices, with parental warmth augmenting parent-child concordance and restrictiveness reducing it. Compared with boys' ideal self, that of girls was more similar to the ideals that parents hold for their children and for themselves. Analyses of patterns over time suggested a growth of ideal-self stability across adolescence. PMID- 17352610 TI - Adaptive memory: survival processing enhances retention. AB - The authors investigated the idea that memory systems might have evolved to help us remember fitness-relevant information--specifically, information relevant to survival. In 4 incidental learning experiments, people were asked to rate common nouns for their survival relevance (e.g., in securing food, water, or protection from predators); in control conditions, the same words were rated for pleasantness, relevance to moving to a foreign land, or personal relevance. In surprise retention tests, participants consistently showed the best memory when words were rated for survival; the survival advantage held across recall, recognition, and for both within-subject and between-subjects designs. These findings suggest that memory systems are "tuned" to remember information that is processed for fitness, perhaps as a result of survival advantages accrued in the past. PMID- 17352611 TI - Additive and interactive effects on response time distributions in visual word recognition. AB - Across 3 different word recognition tasks, distributional analyses were used to examine the joint effects of stimulus quality and word frequency on underlying response time distributions. Consistent with the extant literature, stimulus quality and word frequency produced additive effects in lexical decision, not only in the means but also in the shape of the response time distributions, supporting an early normalization process that is separate from processes influenced by word frequency. In contrast, speeded pronunciation and semantic classification produced interactive influences of word frequency and stimulus quality, which is a fundamental prediction from interactive activation models of lexical processing. These findings suggest that stimulus normalization is specific to lexical decision and is driven by the task's emphasis on familiarity based information. PMID- 17352612 TI - Forgetting and learning potentiation: dual consequences of between-session delays in cognitive skill learning. AB - In the cognitive skill literature, between-session delays have been treated either as having a negligible effect on performance or as causing forgetting. In contrast, in the procedural skill literature, overnight between-session delays can result in performance gains. In 5 multi-session data sets, the author demonstrates that neither of these 2 models holds for the case of cognitive skill learning. Instead, the delay between sessions appeared to yield both forgetting and enhanced potential for new learning. Two candidate classes of explanation are considered, and implications for the empirical law of learning are discussed. PMID- 17352613 TI - On the dynamic nature of response criterion in recognition memory: effects of base rate, awareness, and feedback. AB - The authors examined whether participants can shift their criterion for recognition decisions in response to the probability that an item was previously studied. Participants in 3 experiments were given recognition tests in which the probability that an item was studied was correlated with its location during the test. Results from all 3 experiments indicated that participants' response criteria were sensitive to the probability that an item was previously studied and that shifts in criterion were robust. In addition, awareness of the bases for criterion shifts and feedback on performance were key factors contributing to the observed shifts in decision criteria. These data suggest that decision processes can operate in a dynamic fashion, shifting from item to item. PMID- 17352614 TI - Aging and the misinformation effect: a neuropsychological analysis. AB - Older adults' susceptibility to misinformation in an eyewitness memory paradigm was examined in two experiments. Experiment 1 showed that older adults are more susceptible to interfering misinformation than are younger adults on two different tests (old-new recognition and source monitoring). Experiment 2 examined the extent to which processes associated with frontal lobe functioning underlie older adults' source-monitoring difficulties. Older adults with lower frontal-lobe-functioning scores on neuropsychological tests were particularly susceptible to false memories in the misinformation paradigm. The authors' results agree with data from other false memory paradigms that show greater false recollections in older adults, especially in those who scored poorly on frontal tests. The results support a source-monitoring account of aging and illusory recollection. PMID- 17352615 TI - The role of inhibitory processes in part-list cuing. AB - Providing a subset of studied items as retrieval cues can have detrimental effects on recall of the remaining items. In 2 experiments, the authors examined such part-list cuing impairment in a repeated testing situation. Participants studied exemplars from several semantic categories and were given 2 successive cued-recall tests separated by a distractor task of several minutes. Part-list cues were provided in the 1st test but not the 2nd. Noncue item recall was tested with the studied category cues (same probes) in the 1st test, but novel, unstudied retrieval cues (independent probes) in the 2nd test. The authors found detrimental effects of part-list cues in both the 1st (same-probe) test and the 2nd (independent-probe) test. These results show that part-list cuing impairment can be lasting and is not eliminated with independent probes. The findings support the view that the impairment was caused by retrieval inhibition. PMID- 17352616 TI - Short cue presentations encourage advance task preparation: a recipe to diminish the residual switch cost. AB - In the task-switching literature, it has frequently been demonstrated that although advance task preparation reduces the switch cost, it never really eliminates the switch cost. This remaining residual switch cost received much attention, and it has been argued that advance preparation is restricted in nature. In the present study, the role of task-cue presentation in the establishment of the residual switch cost was investigated. In 4 experiments, the cue was removed during the preparation interval, and it was hypothesized that this would encourage participants to complete advance task preparation. The results of all 4 experiments provided support for this hypothesis: When the cue was presented for a short time and then removed, the residual switch cost completely disappeared. This was found for different cue types. Furthermore, Experiment 3 demonstrated that it was not the presence of the cue itself but merely differences in advance task preparation that caused the effects. This suggests that advance task preparation is not as restricted in nature as previously assumed. PMID- 17352617 TI - You said it before and you'll say it again: expectations of consistency in communication. AB - Repeated reference creates strong expectations in addressees that a speaker will continue to use the same expression for the same object. The authors investigate the root reason for these expectations by comparing a cooperativeness-based account (Grice, 1975) with a simpler consistency-based account. In two eye tracking experiments, the authors investigated the expectations underlying the effect of precedents on comprehension. The authors show that listeners expect speakers to be consistent in their use of expressions even when these expectations cannot be motivated by the assumption of cooperativeness. The authors conclude that though this phenomenon seems to be motivated by cooperativeness, listeners' expectation that speakers be consistent in their use of expressions is governed by a general expectation of consistency. PMID- 17352618 TI - Task switching versus cue switching: using transition cuing to disentangle sequential effects in task-switching performance. AB - Recent methodological advances have allowed researchers to address confounds in the measurement of task-switch costs in task-switching performance by dissociating cue switching from task switching. For example, in the transition cuing procedure, which involves presenting cues for task transitions rather than for tasks, cue transitions (cue switches and cue repetitions) and task transitions (task switches and task repetitions) can be examined in a complete factorial design. Transition cuing removes the confound between cue transitions and first-order task transitions, but it introduces a confound between cue transitions and longer task sequences. In the present study, transition cuing was studied with two cues per transition (REPEAT and AGAIN for task repetitions; SWITCH and CHANGE for task switches), enabling a partial deconfounding of cue transitions and task sequences. Two experiments revealed robust sequential effects, with higher order task transitions affecting performance when cue transitions were held constant and with cue transitions affecting performance when task sequences were held constant. Methodological and theoretical implications of these findings for research on task switching are discussed. PMID- 17352619 TI - Recognition memory for novel stimuli: the structural regularity hypothesis. AB - Early studies of human memory suggest that adherence to a known structural regularity (e.g., orthographic regularity) benefits memory for an otherwise novel stimulus (e.g., G. A. Miller, 1958). However, a more recent study suggests that structural regularity can lead to an increase in false-positive responses on recognition memory tests (B. W. A. Whittlesea & L. D. Williams, 1998). In the present study the authors attempted to identify the circumstances under which structural regularity benefits old-new discrimination and those under which it leads to an increase in false-positive responses. The highly generalizable tendency shown here is for structural regularity to benefit old-new discrimination. The increase in false-positive responses for structurally regular novel items may be limited to situations in which regularity is confounded with similarity to studied items. PMID- 17352620 TI - Implicit learning of semantic category sequences: response-independent acquisition of abstract sequential regularities. AB - Through the use of a new serial naming task, the authors investigated implicit learning of repeating sequences of abstract semantic categories. Participants named objects (e.g., table, shirt) appearing in random order. Unbeknownst to them, the semantic categories of the objects (e.g., furniture, clothing) followed a repeating sequence. Irrespective of whether participants were instructed to attend to the categories (Experiment 1) or whether no mention was made of the categories (Experiments 2 and 3), naming latencies reliably increased when the repeating category sequence was switched to a random sequence. This was the case even for participants showing no explicit knowledge in reproduction and recognition tests. Results indicate that abstract sequential structures are learned implicitly, even if neither the surface stimuli nor the responses follow a sequence. PMID- 17352621 TI - Interference effects from grammatically unavailable constituents during sentence processing. AB - Evidence from 3 experiments reveals interference effects from structural relationships that are inconsistent with any grammatical parse of the perceived input. Processing disruption was observed when items occurring between a head and a dependent overlapped with either (or both) syntactic or semantic features of the dependent. Effects of syntactic interference occur in the earliest online measures in the region where the retrieval of a long-distance dependent occurs. Semantic interference effects occur in later online measures at the end of the sentence. Both effects endure in offline comprehension measures, suggesting that interfering items participate in incorrect interpretations that resist reanalysis. The data are discussed in terms of a cue-based retrieval account of parsing, which reconciles the fact that the parser must violate the grammar in order for these interference effects to occur. Broader implications of this research indicate a need for a precise specification of the interface between the parsing mechanism and the memory system that supports language comprehension. PMID- 17352622 TI - The testing effect in recognition memory: a dual process account. AB - The testing effect, or the finding that taking an initial test improves subsequent memory performance, is a robust and reliable phenomenon--as long as the final test involves recall. Few studies have examined the effects of taking an initial recall test on final recognition performance, and results from these studies are equivocal. In 3 experiments, we attempt to demonstrate that initial testing can change the ways in which later recognition decisions are executed even when no difference can be detected in the recognition hit rates. Specifically, initial testing was shown to enhance later recollection but leave familiarity unchanged. This conclusion emerged from three dependent measures: source memory, exclusion performance, and remember/know judgments. PMID- 17352623 TI - The effect of working memory capacity limitations on the intuitive assessment of correlation: amplification, attenuation, or both? AB - This article challenges Yaakov Kareev's (1995a, 2000) argument regarding the positive bias of intuitive correlation estimates due to working memory capacity limitations and its adaptive value. The authors show that, under narrow window theory's primacy effect assumption, there is a considerable between-individual variability of the effects of capacity limitations on the intuitive assessment of correlation, in terms of both sign and magnitude: Limited capacity acts as an amplifier for some individuals and as a silencer for others. Furthermore, the average amount of attenuation exceeds the average amount of amplification, and the more so, the smaller the capacity. Implications regarding the applicability and contribution of the bias notion in this context and the evaluation of the adaptive value of capacity limitations are discussed. PMID- 17352624 TI - Independent retrieval of source dimensions: an extension of results by Starns and Hicks (2005) and a comment on the ACSIM measure. AB - Recently, J. J. Starns and J. L. Hicks (2005) have argued that source dimensions are retrieved independently from memory. In their innovative experiment, manipulating the retrievability of 1 source feature did not affect memory for a 2nd feature. Following C. S. Dodson and A. P. Shimamura (2000), the authors argue that the source memory measure that Starns and Hicks used (known as the average conditional source identification measure) is vulnerable to a response bias in this particular paradigm, and this may undermine Starns and Hicks's conclusion. Starns and Hicks, however, acknowledged this possibility. The authors substantiate this claim by a simulation and by replicating Starns and Hicks's experiment. In 2 further experiments, the authors use an extended multinomial model to analyze data showing that Starns and Hicks's conclusion holds even if results cannot be attributed to response biases. PMID- 17352625 TI - Qualitative differences between the joint effects of stimulus quality and word frequency in reading aloud and lexical decision: extensions to Yap and Balota (2007). AB - There have been multiple reports over the last 3 decades that stimulus quality and word frequency have additive effects on the time to make a lexical decision. However, it is surprising that there is only 1 published report to date that has investigated the joint effects of these two factors in the context of reading aloud, and the outcome of that study is ambiguous. The present study shows that these factors interact in the context of reading aloud and at the same time replicate the standard pattern reported for lexical decision. The main implication of these results is that lexical activation, at least as indexed by the effect of word frequency, does not unfold in a uniform way in the contexts reported here. The observed dissociation also implies, contrary to J. A. Fodor's (1983) view, that the mental lexicon is penetrable rather than encapsulated. The distinction between cascaded and thresholded processing offers one way to understand these and related results. A direction for further research is briefly noted. PMID- 17352628 TI - Obesity and rural health--a neglected risk factor for knee osteoarthritis. PMID- 17352629 TI - Incongruities of science, medicine, and politics. PMID- 17352630 TI - Er:YAG laser osteotomy based on refined computer-assisted presurgical planning: first clinical experience in oral surgery. AB - OBJECTIVE: This case report was aimed at primary clinical experience concerning surgical extraction of a displaced tooth with the help of the Er:YAG laser based on refined computer-assisted presurgical planning. METHODS: The case refers to the extraction of a displaced maxillary canine in a female patient. For the osteotomy, a pulsed Er:YAG laser was applied with pulse energy of 500 mJ, pulse duration of 250 microsec and pulse frequency of 12 Hz. The fiber tip (1000 microm) was kept with a 1-2 mm distance to the bone surface. Refined presurgical computer-assisted planning was performed with regard to minimization of bone loss, especially for the sake of preservation of the alveolar ridge. Based on a detailed three-dimensional (3D) reconstruction of the patient's anatomy, dynamical simulations of a buccal and a palatinal variant of access osteotomy were provided. Additionally, a volumetric profile of bone tissue quality based on Hounsfield values was generated. RESULTS: By means of the 3D reconstruction and the tissue quality profile, both bone thickness and quality was evaluated as superior in the palatinal rather than in the vestibular part. Therefore, a classical buccal access window was chosen. The laser osteotomy allowed an exact cut geometry without any thermal damage and merely minimal bone loss. CONCLUSION: The enhanced possibilities by laser osteotomy allowed for full exploitation of presurgical planning. As regards the actual case, computer-assisted planning was of benefit for an appropriate choice of access osteotomy by enabling evaluation of the consistency of the bony structures. PMID- 17352631 TI - Effect of a novel Er:YAG laser in caries removal and cavity preparation: a clinical observation. AB - OBJECTIVE: We evaluated the applicability of a novel Er:YAG laser under clinical conditions. BACKGROUND DATA: The Er:YAG laser has been demonstrated to be a safe and effective alternative to the conventional turbine bur, but the relatively low cutting speed prevented the wide application of Er:YAG laser in clinical cavity preparation. METHODS: A Smart 2940 D laser developed by Deka Corporation was used for cavity preparation in 95 teeth of 45 patients. Parameters were as follows: wavelength 2.94 microm, pulse energy 700 mJ, repetition rate 8 Hz. Pain, discomfort, assessment during cavity preparation, prognosis factor, and overall clinical evaluation were assessed during or after treatment. RESULTS: No adverse reaction was observed in any tooth. No intraoperative pain or only slight intraoperative pain was described in 85 teeth (89.5%). Cavity preparation was completed with the laser system alone in 90 teeth (94.7%). Overall clinical evaluation showed no safety problems, with a very good or good rating in 86 teeth (90.5%). The overall operation time was 49 sec on average. CONCLUSION: The Smart 2940 D is an efficient, effective, safe, and suitable instrument for caries removal and for cavity preparation. It greatly shortens operation time. PMID- 17352632 TI - Laser acupuncture in knee osteoarthritis: a double-blind, randomized controlled study. AB - OBJECTIVE: The purpose of this study was to investigate the effects and minimum effective dose of laser acupuncture in knee osteoarthritis (KOA), and to determine if it is superior to placebo treatment (sham) in the evaluation of clinical-functional outcome and quality of life. METHODS: In this randomized, placebo-controlled study, patients with grade 2 and 3 primary KOA were selected. Group I (n = 27) received 904-nm low-level laser irradiation with 10 mW/cm(2) power density, 4 mW output power, 0.4 cm(2) spot size, 0.48 J dose per session, and 120-sec treatment time on the medial side of the knee to the acupuncture point Sp9. Group II (n = 25) received placebo-laser therapy at the same place on the same point. Patients in both of the groups had treatment 5 days per week (total duration of therapy was 10 days) and 20 min per day. The study was comprised of a 2-week (10-session) intervention. Participants were evaluated before treatment (baseline), after treatment (2nd week), and at the 12th week. In this double-blind study, a blind examiner carried out all outcome assessments. The main outcome measures were as follows: pain on movement (pVAS), 50-foot walking time (50 foot w), knee circumference (KC), medial tenderness score (MTS), Western Ontario and McMaster Universities osteoarthritis index (WOMAC), and Nottingham Health Profile (NHP). RESULTS: Statistically significant improvement was observed in PVAS, 50 foot w, and KC in group 1. In Group II, statistically significant improvement was observed in PVAS, 50 foot w, and WOMAC. When groups were compared with each other, the improvement observed in KC was superior in Group I at the 2(nd) week (p = 0.005). CONCLUSION: Laser acupuncture was found to be effective only in reducing periarticular swelling when compared with placebo laser. PMID- 17352633 TI - Laser needle acupuncture at Neiguan (PC6) does not mediate heart rate variability in young, healthy men. AB - OBJECTIVE: The aim of this randomized, double-blinded, placebo-controlled trial was to evaluate specific effects of laser needle acupuncture at the Neiguan point (PC6) on sympathetic and parasympathetic nerve activity in healthy subjects using heart rate variability (HRV) analysis. BACKGROUND DATA: Acupuncture at the Neiguan point (PC6) has been shown to modulate the autonomic nervous system. METHODS: Forty-five healthy non-smoking males were randomly divided into a placebo group (n = 20) with no laser irradiation and into an intervention group (n = 25) for which laser needle irradiation (36.8 kJ/cm(2)) was performed on the right forearm. Monitoring of HRV was performed before, during, and after intervention. RESULTS: Repeated-measures MANOVA did not show statistically significant main effects of time (F = 1.29, p = 0.27) or of group (F = 1.67, p = 0.16). The time by group interaction was also not statistically significant (F = 0.95, p = 0.54). CONCLUSION: Our results suggest that heart rate variability was not influenced by laser needle acupuncture at the Neiguan point (PC6). PMID- 17352634 TI - Effect of energy and pulse repetition rate of Er: YAG laser on dentin ablation ability and morphological analysis of the laser-irradiated substrate. AB - OBJECTIVE: The aim of this study was to assess the effect of energy and pulse repetition rate of the Er:YAG laser (2.94 microm) on dentin ablation ability and substrate morphology. BACKGROUND DATA: Previous studies have demonstrated the ability of the Er:YAG laser for ablating dentin substrate. METHODS: Fifteen crowns of molars were sectioned in four fragments, providing 60 samples, which were ground to expose dentin. Initial mass was obtained by weighing the fragments. Twelve groups were randomly formed, according to the combination of laser energies (200, 250, 300, and 350 mJ) and pulse repetition rates (2, 3, and 4 Hz), usually advised for cavity preparation. The final mass was obtained, and dentin mass loss was calculated by the difference between the final and initial mass. Afterwards, specimens were prepared for scanning electron microscopy (SEM). Data were submitted to analysis of variance (ANOVA) and Scheffe test (p < 0.05). RESULTS: Pulse repetition rate of 4 Hz was statistically similar to 3 Hz, and laser energy of 350 mJ was statistically similar to 300 mJ. Increased pulse repetition rates provided higher ablation depth and slight enlargement of dentinal tubules, whereas increased energies yielded greater ablation of intertubular dentin. CONCLUSION: The ablation ability of the Er:YAG laser on dentin raised with the increase of energy and/or pulse repetition rate, the latter exhibiting a stronger influence on mass loss rate and on morphological alterations. PMID- 17352635 TI - Laser therapy in the treatment of carpal tunnel syndrome: a randomized controlled trial. AB - OBJECTIVE: This prospective, randomized, placebo-controlled trial aimed to investigate the efficacy of laser therapy in the treatment of carpal tunnel syndrome (CTS). BACKGROUND DATA: Low-level laser therapy (LLLT) has been found to have positive effects in the treatment of CTS and various musculoskeletal conditions. METHODS: A total of 81 patients were included in this study. Diagnosis of CTS was based on both clinical examination and electromyographic (EMG) study. Patients were randomly assigned into two groups. Group 1 (n = 41) underwent laser therapy (7 joules/2 min) over the carpal tunnel area. Group 2 (n = 40) received placebo laser therapy. All patients received therapy five times per week, for a total of 10 sessions. Patients also used a wrist splint each night. Patients were assessed according to pain, hand-pinch grip strength, and functional capacity. Pain was evaluated by Visual Analog Scale (VAS; day-night). Hand grip was measured by Jamar dynometer, and pinch grip was measured by pinchmeter. Functional capacity was assessed by a self-administered questionnaire for severity of symptoms. RESULTS: The mean age of the patients (70 women, 11 Men) was 49.3 +/- 11.0 (range, 26-78). After therapy there were statistically significant improvements in VAS, pinch grip, and functional capacity measurement in both groups (p < 0.001). Hand grip was found to have been improved in the laser group. In EMG, there were statistically improvements in sensory nerve velocity, and sensory and motor distal latancies in the laser group (p < 0.001). Only sensory nerve velocity was meaningful in the placebo group. CONCLUSION: In using LLLT, (1) there was no difference relative to pain relief and functional capacity during the follow-up in CTS patients; (2) there were positive effects on hand and pinch grip strengths. PMID- 17352636 TI - Percutaneous laser disc decompression for lumbar disc hernia: indications based on Lasegue's Sign. AB - OBJECTIVE: The present study was conducted to establish reasonable indications of patient neurological manifestations for use of percutaneous laser disc decompression (PLDD). BACKGROUND DATA: PLDD is a less invasive surgical procedure for lumbar disc hernia, whose indications have been described on the basis of radiographical findings. METHODS: Sixty-five consecutive patients (45 men and 20 women) with lumbar disc hernia were treated with PLDD by applying a diode laser (wavelength 805 nm). A total of 450-1,205 joules (average, 805.5 joules) were delivered per disc. All patients suffered from radicular pain. They were divided based on the presence of Lasegue's sign. The post-procedure results at 1 week and 1 year were compared between the groups. RESULTS: PLDD was effective for patients with Lasegue's sign (80.0%), but ineffective for those without the sign. CONCLUSION: The present study suggests that Lasegue's sign in patients is an indication of PLDD for lumbar disc hernia. PMID- 17352637 TI - Excision biopsy of tongue lesions by diode laser. AB - OBJECTIVE: The aim of this study was to evaluate the diode laser in excision biopsy of superficial proliferative tongue lesions under local anesthesia. BACKGROUND DATA: Most mobile tongue lesions present as surface projections and have similar clinical features. They are usually excised for diagnostic purposes using conventional surgery or electrosurgery. The diode laser has proven itself useful in different oral surgeries. METHODS: We report the results of a prospective pilot study where contact diode laser was used in excision biopsy of six mobile tongue lesions. All excised tissues were pathologically examined. To assess post-operative pain, patients were asked to correlate it to an 11-point Visual Analogue Scale (VAS); patients were also asked to assess their impression of alteration in tongue size on a 4-point scale. Healing, functional results, and recurrence rate were assessed. RESULTS: All interventions were uneventful and done at the same out-patient setting. All lesions were benign. Healing occurred by secondary intention in the six cases with no residual ulceration. Postoperative pain was mild in four cases, while two cases suffered from moderate pain. Post-operative impression of tongue swelling occurred in all cases. The mild impression disappeared by the end of the first week and the moderate one by the end of the second week. No recurrence was observed over a mean follow-up period of 15 months. CONCLUSION: The diode 980-nm laser is optimal for excision biopsy of superficial and benign proliferative lesions of the mobile tongue. PMID- 17352638 TI - Effects of treatment for manipulation of teeth and Er:YAG laser irradiation on dentin: a Raman spectroscopy analysis. AB - OBJECTIVE: The main purpose of this study was to evaluate the utility of Raman spectroscopy analysis as a research tool to study the effects of Er:YAG laser etching on dentin mineral and organic components. A secondary aim was to study the effects of the decontamination process and the storage procedure on dentin components. BACKGROUND DATA: There are no spectroscopy reports relating the effects of Er:YAG laser irradiation as an alternative to acid etching and the manipulation process on the dentin structure. METHODS: Twelve non-carious human third molars were divided in two main groups: stored in thymol solution (group A, n = 6) or autoclaved (group B, n = 6). The specimens were either etched with 37% phosphoric acid (control subgroup) or irradiated with Er:YAG laser. Irradiated samples were divided into the following subgroups: I, II, and III (80 mJ, 3 Hz, 30 sec; 120 mJ, 3 Hz, 30 sec; and 180 mJ, 3 Hz, 30 sec, respectively). Samples were analyzed by Raman spectroscopy. RESULTS: The mineral and organic dentin contents were more affected in autoclaved teeth than in the specimens stored in thymol. Peak area reduction in group A specimens treated with phosphoric acid and pulse energy of 80 mJ were the most conservative surface treatments regarding changes in the peak area of organic and inorganic dentin components. CONCLUSION: The autoclaving process and pulse energies of 120 and 180 mJ produced greater reduction of organic and inorganic contents in dentin, associated with greater reduction in the areas of 968, 1077, 1460, and 1670 cm(1) Raman peaks. PMID- 17352640 TI - Percutaneous laser disc decompression. PMID- 17352643 TI - Sex differences of human trabecular bone microstructure in aging are site dependent. AB - In this study, we characterize bone microstructure, specifically sex differences, at multiple skeletal sites in 165 subjects >52 yr of age, using microCT technology in vitro. Significant sex differences are observed at the distal radius, femoral neck, and femoral trochanter, but not at the iliac crest, calcaneus, and lumbar vertebral body. Correlations in BV/TV between sites ranged from r = 0.13 to 0.56. INTRODUCTION: The goals of this study were (1) to assess potential sex differences of bone microstructure and their difference between skeletal sites and (2) to explore the relationship of trabecular microstructural properties between relevant skeletal sites. MATERIALS AND METHODS: Trabecular bone microstructural properties were measured in vitro in 165 subjects 52-99 yr of age using microCT. Defined volumes of interest (cylinders with 6 mm diameter and 6 mm length) were scanned at a resolution of 26 microm (isotropic) in six different anatomical sites: distal radius, femoral neck and trochanter, iliac crest, calcaneus, and second lumbar vertebral body. RESULTS: At the radius and femoral neck, trabecular bone displayed a more plate-like structure, thicker trabeculae, smaller separation/higher trabecular number, higher connectivity, and a higher degree of anisotropy in men than in women (p < 0.05). At the trochanter, men displayed more plate-like structure and thicker trabeculae (p < 0.05), but no differences in trabecular separation or other parameters compared with the women. At the calcaneus, iliac crest, and second lumbar vertebra none of the bone parameters displayed significant differences between sexes. The BV/TV at one site explained a range of only 2-32% of the variability at other sites. CONCLUSIONS: These results suggest that trabecular bone microstructural properties are remarkably heterogeneous throughout the skeleton. Significant differences between men and women are observed at some, but not at all, sites. The magnitude of sex differences in trabecular microstructure coincides with that of fracture incidence observed for some of the sites in epidemiological studies. PMID- 17352644 TI - Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats. AB - We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. INTRODUCTION: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. MATERIALS AND METHODS: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8-16 wk. Long bones were subjected to microCT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. RESULTS: In the prevention mode, low doses (0.1 and 0.3 microg) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 microg TSH had increased BMD (10-11%), trabecular bone volume (100-130%), trabecular number (25 40%), trabecular thickness (45-60%), cortical thickness (5-16%), mineral apposition and bone formation rate (200-300%), and enhanced mechanical strength of the femur (51-60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. CONCLUSIONS: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling. PMID- 17352645 TI - Bivariate whole genome linkage analysis for femoral neck geometric parameters and total body lean mass. AB - A genome-wide bivariate analysis was conducted for femoral neck GPs and TBLM in a large white sample. We found QTLs shared by GPs and TBLM in the total sample and the sex-specific samples. QTLs with potential pleiotropy were also disclosed. INTRODUCTION: Previous studies have suggested that femoral neck cross-section geometric parameters (FNCS-GPs), including periosteal diameter (W), cross sectional area (CSA), cortical thickness (CT), buckling ratio (BR), and section modulus (Z), are genetically correlated with total body lean mass (TBLM). However, the shared genetic factors between them are unknown. MATERIALS AND METHODS: To identify the specific QTLs shared by FNCS-GPs and TBLM, we performed bivariate whole genome linkage analysis (WGLA) in a large sample of 451 white families made up of 4498 subjects. RESULTS: Multipoint bivariate linkage analyses for 22 autosomes showed evidence of suggestive or significant linkages (thresholds of LOD = 2.3 and 3.7, respectively) to chromosomes 3q12 and 20q13 in the entire sample, 6p25 and 10q24 in women, and 4p15, 5q34-35 and 7q21 in men. Two-point linkage analyses for chromosome X showed strong linkage to Xp22.13, Xp11.4, Xq22.3, Xq23-24, and Xq25. Complete pleiotropy was identified on 10q24 and 5q35 for TBLM and BR in women and for TBLM and CT in men, respectively. Furthermore, chromosomes 5q34-35, 7q21, 10q24, 20q13, Xp22.13, Xp11.4, and Xq25 are also of importance because of their linkage to multiple trait pairs. For example, linkage to chromosome 10q24 was found for TBLM x W (LOD = 2.31), TBLM x CT (LOD = 2.51), TBLM x CSA (LOD = 2.51), TBLM x BR (LOD = 2.64), and TBLM x Z (LOD = 2.55) in women. CONCLUSIONS: In this study, we identified several genomic regions (e.g., 3q12 and 20q13) that seem to be linked to both FNCS-GPs and TBLM. These regions are of interesting because they may harbor genes that may contribute to variation in both FNCS-GPs and TBLM. PMID- 17352646 TI - Cinacalcet in the management of tumor-induced osteomalacia. AB - Both FGF-23 and PTH inhibit renal phosphate reabsorption. We treated two patients with TIO and FGF-23-mediated hypophosphatemia with cinacalcet to test the hypothesis that medicinally induced hypoparathyroidism would decrease renal phosphate wasting. Cinacalcet treatment resulted in increased renal phosphate reabsorption, allowed for a decrease in phosphate supplementation, and showed evidence of bone healing in one of the two patients. INTRODUCTION: Tumor-induced osteomalacia (TIO) is a rare, acquired disease of renal phosphate wasting, which results in hypophosphatemia and osteomalacia. It is caused by mesenchymal tumors that produce the phosphate and vitamin D-regulating hormone, fibroblast growth factor (FGF)-23. Removal of the tumor is curative, but the tumors are often difficult to locate. Medical treatment involves high doses of oral phosphate and calcitriol, but the phosphate is often poorly tolerated and leads to diarrhea. Because PTH also promotes phosphaturia, and patients with hypoparathyroidism are hyperphosphatemic in the setting of elevated serum FGF-23, we postulated that the calcium-sensing receptor agonist, cinacalcet, which can induce hypoparathyroidism, would be an effective adjuvant in the treatment of TIO. MATERIALS AND METHODS: Two subjects with presumed TIO in whom the tumor was not located after extensive testing and who did not tolerate medical therapy with phosphorus and calcitriol were treated with cinacalcet. RESULTS: Neither treatment with phosphorus nor combined treatment with phosphorus and calcitriol had an effect on serum FGF-23 levels. Treatment with cinacalcet resulted in increased renal phosphate reabsorption and serum phosphorus and allowed for a decrease in phosphate supplementation to a dose that was tolerated. On this regimen, one patient showed significant bone healing as shown by resolution of activity on bone scan and lack of osteomalacia as assessed by histomorphometry. CONCLUSIONS: These data show that medically induced hypoparathyroidism with cinacalcet is a therapeutic option for disorders of FGF-23-mediated hypophosphatemia and that, in the absence of PTH, the phosphaturic effect of FGF 23 is decreased. PMID- 17352647 TI - Differential effects of vitamin D analogs on vascular calcification. AB - We tested the effects of calcitriol and its analog paricalcitol on VSMC calcification in vitro and in vivo. For that reason, cells and animals with five sixths nephrectomy were treated with both compounds. Calcitriol, but not paricalcitol, increased VSMC calcification in vitro and in vivo independently of calcium and phosphate levels. This increase in calcification was parallel to an increase in the RANKL/OPG ratio. INTRODUCTION: Vascular calcification is a common finding in patients with endstage renal disease. Furthermore, those patients often present secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Thus, one of the main therapeutic options is to treat those patients with calcitriol or analogs. However, this treatment presents unwanted side effects, such as increases in vascular calcification. MATERIALS AND METHODS: We tested the effect on vascular smooth muscle cell (VSMC) calcification of calcitriol and one of its analogs, paricalcitol, in vitro and in vivo in animals with endstage renal disease. RESULTS: Calcitriol increased calcification of VSMCs cultured in calcification media. This effect was not present when cells were incubated with paricalcitol. Furthermore, only cells incubated with calcitriol showed an increased RANKL/osteoprotegerin (OPG) expression. Animals with renal failure treated with hypercalcemic doses of calcitriol and paricalcitol showed an increase in systolic blood pressure. However, diastolic blood pressure only raised significantly in those animals treated with paricalcitol. This effect led to a significant increase in pulse pressure in animals treated with calcitriol. The increase in pulse pressure was likely caused by the extensive calcification observed in arteries of animals treated with calcitriol. This increase in calcification was not seen in arteries of animals treated with paricalcitol, despite having similar levels of serum calcium and phosphorus as animals treated with calcitriol. Furthermore, the decreases in serum PTH levels were similar in both treatments. CONCLUSIONS: We conclude that paricalcitol has a different effect than calcitriol in VSMC calcification and that this could explain part of the differences observed in the clinical settings. PMID- 17352648 TI - High serum IGFBP-2 is predictive of increased bone turnover in aging men and women. AB - Elevated serum IGFBP-2 is associated with lower BMD in men and women. It is unknown whether IGFBP-2 serves as a negative regulator of bone metabolism by decreasing bone formation or increasing bone resorption. Studying an age stratified community-based sample of 344 men and 276 women, IGFBP-2 was the strongest predictor of increased bone resorption among the IGF/IGFBPs studied. INTRODUCTION: Serum insulin-like growth factor binding protein-2 (IGFBP-2), which increases with age, is a predictor of low BMD among aging men and women. However, it is unknown whether IGFBP-2 negatively influences bone metabolism by decreasing bone formation or increasing bone resorption. Few have examined the relation between the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) with bone turnover markers. MATERIALS AND METHODS: In an age-stratified, random sample of the community, we examined the association between serum IGF-I, IGF-II, IGFBP-1, -2, and -3, and bone turnover markers before and after adjustment for potential confounders (age, body mass index, bioavailable estradiol and testosterone, and sex hormone binding globulin). Analyses were stratified by sex and menopausal status. RESULTS: We studied 344 men (age range, 23-90 yr) and 276 women (age range, 21-93 yr; 166 postmenopausal) not on oral contraceptives or hormone replacement. Among the IGF/IGFBPs assessed, IGFBP-2 was the strongest and most consistent predictor of bone turnover in men and women. After adjustment for potential confounders, IGFBP-2 was positively associated with osteocalcin (OC) and urine and serum N-teleopeptide (NTX) in men (r = 0.20, 0.26, and 0.23, respectively; p < 0.001), serum C-telopeptide (CTX) in premenopausal women (r = 0.28; p < 0.01), and OC, urine NTX, and serum CTX in postmenopausal women (r = 0.24, 0.33, and 0.19, respectively; p < 0.05). CONCLUSIONS: Higher serum IGFBP-2, which is predictive of lower BMD, is associated with increased markers of bone resorption, independent of age, body mass, and sex hormones. The association between IGFBP-2 and markers of bone formation may reflect coupling with increased bone resorption, which is not adequate to maintain BMD. PMID- 17352649 TI - Juvenile Paget's disease: the second reported, oldest patient is homozygous for the TNFRSF11B "Balkan" mutation (966_969delTGACinsCTT), which elevates circulating immunoreactive osteoprotegerin levels. AB - The oldest person (60 yr) with juvenile Paget's disease is homozygous for the TNFRSF11B mutation 966_969delTGACinsCTT. Elevated circulating levels of immunoreactive OPG and soluble RANKL accompany this genetic defect that truncates the OPG monomer, preventing formation of OPG homodimers. INTRODUCTION: Juvenile Paget's disease (JPD), a rare autosomal recessive disorder, features skeletal pain, fracture, and deformity from extremely rapid bone turnover. Deafness and sometimes retinopathy also occur. Most patients have diminished osteoprotegerin (OPG) inhibition of osteoclastogenesis caused by homozygous loss-of-function defects in TNFRSF11B, the gene that encodes OPG. Circulating immunoreactive OPG (iOPG) is undetectable with complete deletion of TNFRSF11B but normal with a 3-bp in-frame deletion. MATERIALS AND METHODS: We summarize the clinical course of a 60-yr-old Greek man who is the second reported, oldest JPD patient, including his response to two decades of bisphosphonate therapy. Mutation analysis involved sequencing all exons and adjacent mRNA splice sites of TNFRSF11B. Over the past 4 yr, we used ELISAs to quantitate his serum iOPG and soluble RANKL (sRANKL) levels. RESULTS: Our patient suffered progressive deafness and became legally blind, although elevated markers of bone turnover have been normal for 6 yr. He carries the same homozygous mutation in TNFRSF11B (966_969delTGACinsCTT) reported in a seemingly unrelated Greek boy and Croatian man who also have relatively mild JPD. This frame-shift deletes 79 carboxyterminal amino acids from the OPG monomer, including a cysteine residue necessary for homodimerization. Nevertheless, serum iOPG and sRANKL levels are persistently elevated. CONCLUSIONS: Homozygosity for the TNFRSF11B "Balkan" mutation (966_969delTGACinsCTT) causes JPD in the second reported, oldest patient. Elevated circulating iOPG and sRANKL levels complement evidence that this deletion/insertion omits a cysteine residue at the carboxyterminus needed for OPG homodimerization. PMID- 17352650 TI - hTERT transcription is repressed by Cbfa1 in human mesenchymal stem cell populations. AB - Human BMSSCs lose telomerase activity in vitro, which leads to chromosomal instability and cellular senescence. We observed an inverse expression pattern between the osteogenic master regulatory gene, CBFA1, and the stem cell associated gene, hTERT. We showed that Cbfa1 acts as a partial repressor of TERT, which may facilitate cellular differentiation. INTRODUCTION: The absence of telomerase activity by cultured human bone marrow stromal stem cells (BMSSCs) causes critical shortening of chromosomal telomeres, leading eventually to cellular senescence. Ex vivo expansion of BMSSCs correlates to an increase in osteogenic lineage associated markers such as alkaline phosphatase, bone sialoprotein, and osteocalcin that are regulated by the master regulatory transcription factor, Cbfa1 (Runx2). This study examined whether Cbfa1 was capable of regulating the promoter of the early stem cell-associated gene, telomerase reverse transcriptase (TERT). MATERIALS AND METHODS: Human BMSSCs were isolated by fluorescence-activated cell sorting. Telomerase activity was determined using the telometric repeat amplification protocol. CBFA1 and TERT gene expression was assessed by real-time PCR. The functional capacity of Cbfa1 to bind to the hTERT promoter was performed using a modified electrophoretic mobility shift assay (EMSA). Chromatin immunoprecipitation (ChIP) analysis was used to examine Cbfa1 binding to the hTERT promoter in vivo. Functional analysis of CBFA-1 wildtype and mutant DNA binding sites on TERT promoter fragments was assessed using the promoterless green fluorescence protein (GFP) reporter vector, pEGFP-1, after transfection into HOS cells. RESULTS: This study showed an inverse expression pattern between the osteogenic master regulatory gene, CBFA1, and the stem cell-associated gene, hTERT. The data showed that BMSSCs undergo osteogenic commitment after the loss of hTERT expression, with concomitant elevated levels of CBFA1 transcripts. In addition, two unique Cbfa1 DNA binding sites were identified on the hTERT proximal promoter by EMSA supershift assay. Mutated forms of the putative Cbfa1 binding sites, created by site-directed mutagenesis, were able to abolish this interaction. ChIP analysis showed that Cbfa1 interacted directly with the hTERT promoter in vivo. Functional studies using GFP reporter constructs, driven by 2- and 3-kbp hTERT proximal promoter fragments, showed significantly lower levels of transcriptional activity compared with corresponding constructs with mutated Cbfa1 binding site Oligo 2. CONCLUSIONS: These studies suggest that Cbfa1 may act as a repressor of early stem cell markers such as hTERT as one possible mechanism for facilitating cellular differentiation. PMID- 17352651 TI - Contribution of trochanteric soft tissues to fall force estimates, the factor of risk, and prediction of hip fracture risk. AB - We compared trochanteric soft tissue thickness, femoral aBMD, and the ratio of fall force to femoral strength (i.e., factor of risk) in 21 postmenopausal women with incident hip fracture and 42 age-matched controls. Reduced trochanteric soft tissue thickness, low femoral aBMD, and increased ratio of fall force to femoral strength (i.e., factor of risk) were associated with increased risk of hip fracture. INTRODUCTION: The contribution of trochanteric soft tissue thickness to hip fracture risk is incompletely understood. A biomechanical approach to assessing hip fracture risk that compares forces applied to the hip during a sideways fall to femoral strength may by improved by incorporating the force attenuating effects of trochanteric soft tissues. MATERIALS AND METHODS: We determined the relationship between femoral areal BMD (aBMD) and femoral failure load in 49 human cadaveric specimens, 53-99 yr of age. We compared femoral aBMD, trochanteric soft tissue thickness, and the ratio of fall forces to bone strength (i.e., the factor of risk for hip fracture, phi), before and after accounting for the force-attenuating properties of trochanteric soft tissue in 21 postmenopausal women with incident hip fracture and 42 age-matched controls. RESULTS: Femoral aBMD correlated strongly with femoral failure load (r2 = 0.73-0.83). Age, height, and weight did not differ; however, women with hip fracture had lower total femur aBMD (OR = 2.06; 95% CI, 1.19-3.56) and trochanteric soft tissue thickness (OR = 1.82; 95% CI, 1.01, 3.31). Incorporation of trochanteric soft tissue thickness measurements reduced the estimates of fall forces by approximately 50%. After accounting for force-attenuating properties of trochanteric soft tissue, the ratio of fall forces to femoral strength was 50% higher in cases than controls (0.92 +/- 0.44 versus 0.65 +/- 0.50, respectively; p = 0.04). CONCLUSIONS: It is possible to compute a biomechanically based estimate of hip fracture risk by combining estimates of femoral strength based on an empirical relationship between femoral aBMD and bone strength in cadaveric femora, along with estimates of loads applied to the hip during a sideways fall that account for thickness of trochanteric soft tissues. Our findings suggest that trochanteric soft tissue thickness may influence hip fracture risk by attenuating forces applied to the femur during a sideways fall and provide rationale for developing improved measurements of trochanteric soft tissue and for studying a larger cohort to determine whether trochanteric soft tissue thickness contributes to hip fracture risk independently of aBMD. PMID- 17352652 TI - Interrelationships between bone microarchitecture and strength in ovariectomized monkeys treated with teriparatide. AB - Bone microarchitecture measured at the iliac crest at 6 mo was confirmed to be a reasonable surrogate for, and a predictor of, architecture and strength of the femoral neck and lumbar vertebra after 18 mo of teriparatide treatment. However, the data taken together showed the importance of cortical bone volume for vertebra to assess pharmacological effects on bone quality. INTRODUCTION: Improvements in bone architecture with teriparatide treatment are suggested to contribute to fracture risk reduction in osteoporotic patients. Teriparatide significantly improves microarchitecture in the iliac crest of humans by stimulating bone modeling and remodeling processes that differ dramatically from those induced by antiresorptives. The relationship between improvements of bone microarchitecture and improvements of bone strength with teriparatide treatment has not yet been fully studied. MATERIALS AND METHODS: Ovariectomized monkeys were administered vehicle (n = 20); teriparatide 1.0 microg/kg/d (n = 19); or teriparatide 5.0 microg/kg/d (n = 21) for 18 mo. Iliac crest biopsies were obtained at 6 and 15 mo after initiation of treatment. Animals were killed after 18 mo of treatment, and adjacent vertebrae or contralateral proximal femora were processed for biomechanical or histomorphometric analyses. Pearson correlation analyses were performed to assess the relationship between biomechanical and static histomorphometric parameters of lumbar vertebra, femoral neck, and iliac crest biopsies. RESULTS: Static histomorphometric parameters of the 6- and 15-mo biopsies were significantly correlated with the vertebral and femoral neck parameters obtained at 18 mo of teriparatide treatment. Iliac crest biopsy parameters at 6 and 15 mo also correlated with vertebral and femoral neck strength at 18 mo. Static histomorphometry of the lumbar vertebra and femoral neck at 18 mo also significantly correlated with strength at these sites. However, cortical bone volume of the lumbar vertebrae had the strongest correlation with vertebral and femoral neck strength (r = 0.74 and 0.71, respectively). CONCLUSIONS: Teriparatide dose dependently improved cortical and trabecular microarchitecture of vertebra and femoral neck, as well as trabecular microarchitecture of the iliac crest. Bone microarchitecture at all sites was significantly correlated with lumbar vertebra and femoral neck strength. Cortical bone volume of vertebra had the strongest correlation with vertebral and femoral neck strength. Therefore, structural improvement seemed to be part of the mechanism for improved strength observed with teriparatide treatment. Trabecular bone architecture of the iliac crest at 6 mo also correlated with vertebral and femoral neck strength, as did femoral neck (cortical and trabecular) histomorphometry and trabecular histomorphometry of vertebra after 18 mo of treatment. Because clinical assessment of cortical bone volume is not readily possible for vertebra noninvasively, these findings confirm the importance of iliac crest biopsies to monitor skeletal health and show that biopsies are a reasonable surrogate to assess spine and femoral neck structure and function. PMID- 17352653 TI - Fidgetin-like 1 gene inhibited by basic fibroblast growth factor regulates the proliferation and differentiation of osteoblasts. AB - The FIGNL1 gene was proven to be a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). In this in vitro study, the AAA proteins inhibited osteoblast proliferation and stimulated osteoblast differentiation. We showed that FIGNL1 may play some regulatory role in osteoblastogenesis. INTRODUCTION: The fidgetin-like 1 (FIGNL1) gene encodes a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). Although the FIGNL1 protein localizes to both the nucleus and cytoplasm, the function of FIGNL1 remains unknown. In a previous study, we identified several genes that mediate the anabolic effects of basic fibroblast growth factor (bFGF) on bone by using microarray data. FIGNL1 was one of the genes that downregulated >2-fold in MC3T3-E1 cells after treatment with bFGF. Therefore, this study was aimed to identify and confirm the function of FIGNL1 on osteoblastogenesis. MATERIALS AND METHODS: We examined the effect of the FIGNL1 gene on proliferation, differentiation, and apoptosis in mouse osteoblast cells (MC3T3-E1 and mouse primary calvarial cells) using flow cytometry, RT-PCR, cell proliferation assay, and cell death assay. MC3T3-E1 cells and mouse calvarial cells were transfected with small interfering RNA (siRNA) directed against the FIGNL1 or nontargeting control siRNA and examined by cell proliferation and cell death assays. Also, FIGNL1 was fused to enhance green fluorescent protein (EGFP), and the EGFP-fused protein was transiently expressed in MC3T3-E1 cells. RESULTS: Reduced expression of FIGNL1 by bFGF and TGF-beta1 treatment was verified by RT PCR analysis. Overexpression of FIGNL1 reduced the proliferation of MC3T3-E1 and calvarial cells, more than the mock transfected control cells did. In contrast, siFIGNL1 transfection significantly increased the proliferation of osteoblasts, whereas overexpression of FIGNL1 did not seem to alter apoptosis in osteoblasts. Meanwhile, overexpression of FIGNL1 enhanced the mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) in osteoblasts. In contrast, siFIGNL1 decreased the expression of ALP and OCN. A pEGFP-FIGNL1 transfected into MCT3-E1 cells had an initially ubiquitous distribution and rapidly translocated to the nucleus 1 h after bFGF treatment. CONCLUSIONS: From these results, we proposed that FIGNL1, a subfamily member of the AAA family of proteins, might play some regulatory role in osteoblast proliferation and differentiation. Further analyses of FIGNL1 will be needed to better delineate the mechanisms contributing to the inhibition of proliferation and stimulation of osteoblast differentiation. PMID- 17352655 TI - Effects of basic fibroblast growth factor and a prostaglandin E2 receptor subtype 4 agonist on osteoblastogenesis and adipogenesis in aged ovariectomized rats. AB - bFGF stimulates osteo- and adipogenesis concurrently at skeletal sites with red but not with fatty marrow, whereas a PGE2 receptor subtype 4 agonist has bone anabolic effects at both skeletal sites and decreases adipose tissue within red and fatty marrow. INTRODUCTION: Basic fibroblast growth factor (bFGF) stimulates osteogenesis at skeletal sites with hematopoietic but not with fatty marrow. The prostaglandin E2 (PGE2) receptor subtype 4 agonist (EP4A) stimulates osteogenesis at the former skeletal sites, but its effects at fatty marrow sites are unknown. In addition, both bFGF and PGE2 through the EP4 receptor have also been implicated in adipogenesis. However, their specific effects on bone marrow adipogenesis and the inter-relationship with osteogenesis have never been studied in vivo. MATERIALS AND METHODS: Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and maintained for 1 yr after surgery. OVX rats were then injected daily with bFGF or with EP4A SC for 3 wk. The osteo- and adipogenic effects of these agents were assessed by histomorphometry and by determining changes in expression of genes associated with these events by real-time PCR in the lumbar and caudal vertebrae, bones with a predominance of hematopoietic and fatty marrow, respectively. Expression of FGFR1-4 and the EP4 receptor were also evaluated by real-time PCR and immunocytochemistry. RESULTS: bFGF and EP4A stimulated bone formation at skeletal sites with hematopoietic marrow, but only the later anabolic agent is also effective at fatty marrow sites. The diminished bone anabolic effect of bFGF at the fatty marrow site was not caused by a lack of cell surface receptors for the growth factor at this site. Interestingly, whereas EP4A decreased fatty marrow area and the number of adipocytes, bFGF increased osteogenesis and adipogenesis within the bone marrow. CONCLUSIONS: bFGF can stimulate osteogenesis and bone marrow adipogenesis concurrently at red marrow sites, but not at fatty marrow sites. In contrast, EP4A stimulates bone formation at skeletal sites with hematopoietic and fatty marrow and simultaneously decreased fatty marrow area and the number of adipocytes in the bone marrow, suggesting that osteogenesis occurs at the expense of adipogenesis. PMID- 17352654 TI - Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts. AB - Osteogenesis is synergistically enhanced by the combined effect of complimentary factors. This study showed that Nell-1 and BMP-2 synergistically enhanced osteogenic differentiation of myoblasts and phosphorylated the JNK MAPK pathway. The findings are important because of the osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of coordinated BMP-2 and Nell-1 delivery. INTRODUCTION: BMPs play an important role in the migration and proliferation of mesenchymal cells and have a unique ability to alter the differentiation of mesenchymal cells toward chondrogenic and osteogenic lineages. Signaling upstream of Cbfa1/Runx2, BMPs effects are not limited to cells of the osteoblast lineage. Thus, additional osteoblast-specific factors that could synergize with BMP-2 would be advantageous for bone regeneration procedures. NELL 1 (NEL-like molecule-1; NEL [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a novel growth factor believed to preferentially target cells committed to the osteochondral lineage. MATERIALS AND METHODS: C2C12 myoblasts were transduced with AdLacZ, AdNell-1, AdBMP-2, or AdNell-1+AdBMP-2 overexpression viruses. Effects were studied by cell morphology, alkaline phosphatase activity, osteopontin production, and MAPK signaling. Additionally, in a nude mouse model, viruses were injected into leg muscles, and new bone formation was examined after 2 and 8 wk. RESULTS: C2C12 myoblasts co transduced with AdNell-1+AdBMP-2 showed a synergistic effect on osteogenic differentiation as detected by alkaline phosphatase activity and osteopontin production. Nell-1 stimulation on AdNell-1 + AdBMP-2 preconditioned C2C12 cells revealed significant activation of the non-BMP-2 associated c-Jun N-terminal kinase (JNK) MAPK signaling pathway, but not the p38 or extracellular signal regulated kinase (ERK1/2) MAPK pathways. Importantly Nell-1 alone did not induce osteogenic differentiation of myoblasts. In a nude mouse model, injection of AdNell-1 alone stimulated no bone formation within muscle; however, injection of AdNell-1+AdBMP-2 stimulated a synergistic increase in bone formation compared with AdBMP-2 alone. CONCLUSIONS: These findings are important because of the confirmed osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of enhanced BMP-2 action with coordinated Nell-1 delivery. PMID- 17352656 TI - Dendritic cells at the osteo-immune interface: implications for inflammation induced bone loss. AB - Within the past decade, the critical roles of T cells and T cell-mediated immunity in inflammation-induced osteoclastogenesis and subsequent bone loss have been extensively studied, thereby establishing the new paradigm of osteoimmunology. Therefore, dendritic cells (DCs), the most potent antigen presenting cells, responsible for activation of naive T cells and orchestration of the immune response, became critically situated at the osteo-immune interface. Today, emerging new evidence suggests that DC may be directly involved in inflammation-induced osteoclastogenesis and bone loss, by acting as osteoclast (OC) precursors that can further develop into DC-derived OCs (DDOC) under inflammatory conditions. These findings have tremendous implications, because in addition to DC's important roles in regulating innate and adaptive immunity, a direct contribution by these cells to inflammation-induced bone loss may provide a promising therapeutic target not only for controlling inflammation but also for modulating bone destruction. PMID- 17352657 TI - Residual lifetime risk of fractures in women and men. AB - In a sample of 1358 women and 858 men, > or = 60 yr of age who have been followed up for up to 15 yr, it was estimated that the mortality-adjusted residual lifetime risk of fracture was 44% for women and 25% for men. Among those with BMD T-scores < or = -2.5, the risks increased to 65% in women and 42% in men. INTRODUCTION: Risk assessment of osteoporotic fracture is shifting from relative risk to an absolute risk approach. Whereas BMD is a primary predictor of fracture risk, there has been no estimate of mortality-adjusted lifetime risk of fracture by BMD level. The aim of the study was to estimate the residual lifetime risk of fracture (RLRF) in elderly men and women. MATERIALS AND METHODS: Data from 1358 women and 858 men > or = 60 yr of age as of 1989 of white background from the Dubbo Osteoporosis Epidemiology Study were analyzed. The participants have been followed for up to 15 yr. During the follow-up period, incidence of low-trauma, nonpathological fractures, confirmed by X-ray and personal interview, were recorded. Incidence of mortality was also recorded. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline. Residual lifetime risk of fracture from the age of 60 was estimated by the survival analysis taking into account the competing risk of death. RESULTS: After adjusting for competing risk of death, the RLRF for women and men from age 60 was 44% (95% CI, 40-48) and 25% (95% CI, 19-31), respectively. For individuals with osteoporosis (BMD T-scores < or = 2.5), the mortality-adjusted lifetime risk of any fracture was 65% (95% CI, 58 73) for women and 42% (95% CI, 24-71) for men. For the entire cohort, the lifetime risk of hip fracture was 8.5% (95% CI, 6-11%) for women and 4% (95% CI, 1.3-5.4%) for men; risk of symptomatic vertebral fracture was 18% (95% CI, 15 21%) for women and 11% (95% CI, 7-14%) for men. CONCLUSIONS: These estimates provide a means to communicate the absolute risk of fracture to an individual patient and can help promote the identification and targeting of high-risk individuals for intervention. PMID- 17352658 TI - Regulation of COX-2 mediates acid-induced bone calcium efflux in vitro. AB - Chronic metabolic acidosis induces net Ca efflux from bone; this osteoclastic bone resorption is mediated by increased osteoblastic prostaglandin synthesis. Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, is present in both constitutive (COX-1) and inducible (COX-2) forms. We report here that acidosis increases both osteoblastic RNA and protein levels for COX-2 and that genetic deficiency or pharmacologic inhibition of COX-2 significantly reduces acid-induced Ca efflux from bone. INTRODUCTION: Incubation of neonatal mouse calvariae in medium simulating physiologic metabolic acidosis induces an increase in osteoblastic prostaglandin E2 (PGE2) release and net calcium (Ca) efflux from bone. Increased PGE2 is necessary for acid-induced bone resorption, because inhibition of cyclooxygenase activity with indomethacin significantly decreases not only PGE2 production but also Ca release. Cyclooxygenase is present in both constitutive (COX-1) and inducible (COX-2) forms. Because COX-2 activity has been implicated in several forms of pathological bone resorption, we tested the hypothesis that COX-2 is critical for acid-induced, cell-mediated bone Ca efflux. MATERIALS AND METHODS: To determine the effect of metabolic acidosis on COX-2 RNA and protein, primary cells isolated from neonatal CD-1 mouse calvariae were cultured in neutral (Ntl) or physiologically acidic medium (Met). RNA levels for COX-2 and COX-1 were measured by quantitative real-time PCR. Levels of COX-2 and COX-1 protein were measured by immunoblot analysis. To determine the effect of acidosis on bone Ca efflux in genetically deficient COX-2 mice, mice heterozygous for the COX-2 knockout (strain B6;129S7-Ptgs2(tm1Jed)/J) were used as breeders, and neonatal calvariae were cultured in Ntl or Met. To determine the effects of the specific COX-2 inhibitor, NS398, on acid-induced bone resorption, CD-1 calvariae were incubated in Ntl or Met with or without NS398 (1 microM). Medium PGE2 was assayed by ELISA. RESULTS: Incubation of mouse calvarial cells in Met significantly increased COX-2 RNA and protein levels without a change in COX-1. Increased COX-2 protein levels in response to Met were also observed in cultured calvariae. Acid-induced, cell-mediated Ca efflux from B6;129S7-Ptgs2(tm1Jed)/J calvariae was dependent on genotype. From 0 to 24 h, when physicochemical Ca efflux predominates, Met significantly increased net Ca efflux in all genotypes. After 24 h, when cell-mediated Ca efflux predominates, Met induced greater Ca efflux from (+/+) than from (+/-), and there was no increase from (-/-). In calvariae from CD-1 mice, NS398 significantly inhibited both the acid-induced increase in PGE2 and Ca release. CONCLUSIONS: The specific acid-induced increase in COX-2 RNA and protein levels and the dependency of the increased Ca efflux on COX-2 activity, as determined by both genetic deficiency and pharmacologic inhibition, show that COX-2 is critical for acid-induced, cell-mediated bone resorption. PMID- 17352659 TI - The nonsense-mediated decay RNA surveillance pathway. AB - Nonsense-mediated mRNA decay (NMD) is a quality-control mechanism that selectively degrades mRNAs harboring premature termination (nonsense) codons. If translated, these mRNAs can produce truncated proteins with dominant-negative or deleterious gain-of-function activities. In this review, we describe the molecular mechanism of NMD. We first cover conserved factors known to be involved in NMD in all eukaryotes. We then describe a unique protein complex that is deposited on mammalian mRNAs during splicing, which defines a stop codon as premature. Interaction between this exon-junction complex (EJC) and NMD factors assembled at the upstream stop codon triggers a series of steps that ultimately lead to mRNA decay. We discuss whether these proofreading events preferentially occur during a "pioneer" round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC. PMID- 17352660 TI - Cell wall-associated mechanisms of disease resistance and susceptibility. AB - The plant cuticle and cell wall separate microbial pathogens from the products of plant metabolism. While microbial pathogens try to breach these barriers for colonization, plants respond to attempted penetration by a battery of wall associated defense reactions. Successful pathogens circumvent or suppress plant nonself recognition and basal defense during penetration and during microbial reproduction. Additionally, accommodation of fungal infection structures within intact cells requires host reprogramming. Recent data highlight that both early plant defense to fungal penetration and host reprogramming for susceptibility can function at the host cell periphery. Genetic evidence has also widened our understanding of how fungal pathogens are restricted during penetration at the plant cell wall. This review summarizes the current view of how plants monitor and model their cell periphery during interaction with microbial invaders. PMID- 17352661 TI - The outcome of patients with sepsis and septic shock presenting to emergency departments in Australia and New Zealand. AB - BACKGROUND: Early goal-directed therapy might benefit patients with sepsis and septic shock in Australia and New Zealand. However, the current treatment and outcome of these patients is unknown. OBJECTIVE: To report the characteristics and outcome of patients with sepsis and septic shock presenting to hospital emergency departments (EDs) in Australia and New Zealand. SETTING: All Australian and New Zealand intensive care units contributing to the Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS APD), 1997-2005. METHODS: Patients with an ICU admission diagnosis of nonurinary or urinary sepsis, or non-urinary or urinary sepsis with shock admitted from EDs between 1 January 1997 and 31 December 2005 were identified from the ANZICS APD. Predictor variables for hospital mortality were analysed using logistic regression. RESULTS: 7649 patients were admitted during the study period. The number of patients admitted per year increased progressively (1997, n= 368 [7.7 admissions per ICU]; 2005, n = 1409 [14.0 admissions per ICU]). Non-urinary sepsis with shock (n =3394, 44.4%) was the commonest admission diagnosis, and urinary sepsis with shock the least common (n = 607, 7.9%). Overall ICU and hospital mortality were 20.9% (n=1513/7250) and 27.6% (n=1980/7172), respectively. Hospital mortality was predicted by hospital type (tertiary, metropolitan, rural or private), patient age, APACHE III score, sepsis classification, mechanical ventilation within the first 24 hours after ICU admission, and calendar year. A significant interaction between sepsis classification and calendar year was demonstrated, with a linear decrease in mortality over time (odds ratio, 0.92; 95% CI, 0.86-0.99; P=0.02). CONCLUSIONS: The reported incidence of sepsis and septic shock in ICU patients presenting to the ED appears to have increased since 1997. In contrast, hospital mortality has decreased. These data require confirmation with a prospective cohort study. PMID- 17352662 TI - C-reactive protein concentration as a predictor of in-hospital mortality after ICU discharge: a nested case-control study. AB - PURPOSE: To assess the ability of potential clinical predictors and inflammatory markers to predict in-hospital mortality after patient discharge from the intensive care unit. SETTING AND PARTICIPANTS: 1272 patients who survived their index admission to a 22-bed multidisciplinary ICU of a university hospital in 2004. DESIGN: Nested case-control study with two concurrent control patients for each case of post-ICU discharge in hospital mortality. RESULTS: There were 29 unexpected in-hospital deaths after ICU discharge (2.3%). C-reactive protein (CRP) concentrations within 24 hours of ICU discharge were available for 14 of these 29 patients and 22 concurrent control patients. CRP concentration at ICU discharge was associated with subsequent mortality (mean CRP concentrations: cases, 204 mg/L v controls, 63 mg/L; P = 0.001). CRP concentration remained significantly associated with post-ICU mortality after adjustment with other potential predictors of mortality (odds ratio [OR] of death for a 10mg/L increase in CRP concentration, 1.27; 95% CI, 1.09-1.49; P = 0.005) and with propensity score (OR, 1.19; 95% CI, 1.05-1.33; P=0.004). The area under the receiver operating characteristic curve for CRP concentrations to predict in-hospital mortality was 0.87 (95% CI, 0.73-0.99; P=0.001). The destination and timing of ICU discharge, SOFA (Sequential Organ Failure Assessment) score, white cell count and fibrinogen concentration at ICU discharge were not significantly associated with in-hospital mortality after ICU discharge. CONCLUSIONS: A high CRP concentration at ICU discharge is an independent predictor of subsequent in hospital mortality. Prospective cohort studies in ICUs with different casemix, discharge criteria and post-ICU mortality rates are needed to validate and generalise our findings. PMID- 17352663 TI - Delirium in the intensive care unit: searching for causes and sources. AB - INTRODUCTION: Currently, diagnosis of delirium in theintensive care unit requires the use of one of a range of screening scales. Publications on delirium in the ICU are increasing, but most focus on psychological markers, with only limited data on physiological indicators of delirium. AIM: To assess the relationship between a range of physiological and treatment markers and the presence of delirium in an ICU cohort. METHODS: Patients admitted to the ICU of a metropolitan tertiary hospital between 1 August 2002 and 31 January 2003 were prospectively screened for delirium using the Intensive Care Delirium Screening Checklist (ICDSC). A retrospective chart review was undertaken to identify potential markers: raised white cell count, neutrophil count, and serum C reactive protein concentration, lactic acidosis, low haemoglobin concentration, use of inotropic support, corticosteroids, or continuous venovenous haemodiafiltration (CVVHDF), and presence of systemic inflammatory response syndrome. Association of these markers with delirium was assessed using chi2 statistics. RESULTS: Of 56 ICU patients who were screened for delirium, charts could be retrieved for 44 (80%): 21 had delirium during the ICU admission, and 23 did not. CVVHDF was the only variable associated with an increased risk of delirium (P=0.03). CONCLUSIONS: Treatment with CVVHDF was the only factor associated with the presence of delirium. Further research is warranted into physiological indicators as adjuncts to psychological assessment scales for delirium. The quest to find a simple biomarker for delirium continues. PMID- 17352664 TI - A technique for the simultaneous measurement of renal ATP, blood flow and pH in a large animal model of septic shock. AB - BACKGROUND: Simultaneous measurement of renal blood flow, renal ATP, renal pH and mean arterial pressure (MAP) might help investigators understand the mechanisms responsible for acute renal failure (ARF) in sepsis. OBJECTIVES: (1) To develop a technique to simultaneously measure MAP, renal blood flow, renal ATP and renal pH in a large mammal during severe sepsis and after circulatory arrest; and (2) To describe preliminary observations during such measurements. METHODS: We implanted a custom-made phosphorus coil around the left kidney and a magnetic resonance compatible blood flow probe around the renal artery of an adult Merino ewe. We induced severe sepsis by intravenous administration of Escherichia coli and obtained 31P magnetic resonance spectroscopic data at 3tesla, and continuous blood flow and MAP data before and during severe sepsis over several hours. We induced circulatory arrest with potassium chloride and measured the same 31P signal immediately and again 30 minutes later. RESULTS: We successfully and simultaneously measured MAP, renal blood flow, renal ATP and renal pH in a large mammal during severe sepsis and induced circulatory arrest. With these techniques, we observed that, despite marked hypotension, there were limited changes in renal ATP and renal pH, and that renal blood flow increased. A rapid and dramatic decrease in ATP and pH occurred with circulatory arrest. CONCLUSIONS: We have developed a technique to simultaneously monitor MAP, renal blood flow, ATP and pH in a large mammal during severe sepsis. Our initial observations indicate preservation of renal ATP in septic shock. PMID- 17352665 TI - Withdrawal of life support and chaplaincy in Australia. AB - OBJECTIVE: To explore the role of health care chaplains in providing pastoral care to patients, their families and clinical staff considering decisions to withdraw life support. METHODS: Quantitative data were obtained retrospectively from a survey of 327 Australian health care chaplains (both staff and volunteer chaplains) to initially identify chaplaincy participation in withdrawal-of-life support issues. Qualitative data were subsequently obtained by in-depth interview of 100 of the surveyed chaplains and thematically coded using the World Health Organization Pastoral Intervention (WHO-PI) codings to explore chaplains' roles. RESULTS: Over half the staff chaplains surveyed (57%) and over a quarter of the volunteer chaplains (28%) indicated that they had been involved with patients or their families in withdrawal-of-life-support decisions. Over a third of staff chaplains (37%) and 16% of volunteer chaplains had assisted clinical staff concerning withdrawal-of-life-support issues. The qualitative data revealed that chaplains were involved with patients, their families and clinical staff at all levels of pastoral intervention, including "pastoral assessment", "pastoral ministry", "pastoral counselling and education" and "pastoral ritual and worship". The specific nature of chaplaincy involvement varied considerably depending on the idiosyncratic issues faced by patients, families and clinical staff. These activities indicated that pastoral care could be provided for the support and benefit of patients, their families and clinical staff facing a complex bioethical issue. CONCLUSIONS: Through a variety of pastoral interventions, some chaplains (mostly staff chaplains) were involved in assisting patients, their families and clinical staff concerning withdrawal-of-life-support issues and thus helped ensure an holistic approach within the health care context. Given this involvement and the future potential benefit for patients, families and clinical staff, there is a need to develop continuing education and research on pastoral care and chaplaincy services. PMID- 17352666 TI - Attitudes of relatives of patients in intensive care and emergency departments to surrogate consent to research on incapacitated participants. AB - BACKGROUND: When potential research participants are incapable of providing consent, it is common for clinicians and researchers to approach family members, attempting to ascertain that person's wishes. Where legally recognised, surrogate consent may also then be provided by relatives for therapy or research involvement. This practice is widely accepted as acknowledging and maintaining patient autonomy, yet there are few data on acceptability of this to the community, or on the accuracy of surrogate decisions. METHODS: We conducted a questionnaire-based survey of 283 people in the waiting rooms of the emergency and intensive care departments of a tertiary hospital in September 2006 to evaluate attitudes to critical care research, willingness to participate if incapacitated, and acceptability of surrogate consent in these circumstances. RESULTS: 283 people were approached with the questionnaire, with 185 people fully completing and returning them: 17% strongly indicated agreement to research participation if they were critically ill, with 25% indicating they would refuse. Only 26% of respondents thought it acceptable that a relative provide consent to research participation on their behalf. Demographic factors did not influence responses, but views of respondents that participation in research was beneficial to participants correlated with an increased willingness to participate themselves. CONCLUSIONS: From our questionnaire, it appears that willingness to participate in research is less than we expected. Surrogate decision-making and the provision of surrogate consent to research was acceptable to only 26% of respondents. PMID- 17352667 TI - Heparin-induced thrombosis with a normal platelet count. AB - Heparin is commonly used in the intensive care unit for preventing and treating thromboembolic disease. One of its more significant complications is heparin induced thrombocytopenia (HIT), an immune-mediated disorder which can provoke an extreme prothrombotic state. We describe an unusual presentation of HIT, where thrombocytopenia was absent. PMID- 17352668 TI - Extreme hypernatraemia: a case report and brief review. AB - A 44-year-old man presented with extreme hypernatraemia. The case is unique in three respects: the patient's plasma sodium concentration was 208mmol/L; the aetiology was multifactorial, including essential hypernatraemia, hypodipsia and high ambient temperature; and the patient survived with full neurological recovery. We briefly review various disorders of thirst and osmorecepters. PMID- 17352669 TI - Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis. AB - BACKGROUND: Loop diuretics are commonly used in critically ill patients with acute renal failure (ARF), but their effect on clinical outcome remains uncertain. We systematically reviewed the literature comparing loop diuretics with control in the management of ARF. METHODS: Studies were identified by search of MEDLINE, EMBASE, and the Cochrane Controlled Clinical Trials Register, and review of proceedings from selected scientific meetings and clinical trial registries, and bibliographies of retrieved citations. We selected randomised controlled trials (RCTs) comparing loop diuretics with control in patients with ARF. Data were extracted in duplicate by two independent reviewers on study characteristics, quality and outcomes. Primary outcomes were mortality, need for renal replacement therapy (RRT) and renal recovery. Secondary outcomes were change to urine output, serum potassium level and acid-base status, duration of ARF or RRT, length of hospital stay and toxicity. RESULTS: Of 62 studies reviewed, five RCTs, enrolling 555 patients, were eligible and analysed. These trials enrolled a mix of patients, but only two included critically ill patients. Overall trial quality was low. There was no statistical difference in mortality (odds ratio [OR], 1.28; 95% CI, 0.89-1.84; P=0.18) or renal recovery (OR, 0.88; 95% CI, 0.59-1.31; P=0.5) with use of loop diuretics compared with control. However, loop diuretics were associated with a shorter duration of RRT (weighted mean difference, ?1.4 days; 95% CI, ?0.2 to ?2.3 days; P=0.02), shorter time to spontaneous decline in serum creatinine level (weighted mean difference, ?2.1 days; 95% CI, ?0.4 to ?3.7 days; P=0.01) and a greater increase in urine output from baseline (OR, 2.6; 95% CI, 1.4-4.9; P=0.004). Insufficient data were available on acid-base status, hospital length of stay or health costs. Four studies reported toxicity, most commonly transient tinnitus and deafness. CONCLUSIONS: Loop diuretics were not associated with improved mortality or rate of independence from RRT, but were associated with shorter duration of RRT and increased urine output. However, these findings have limited relevance to critically ill patients. The relative paucity of high-quality data assessing the value of loop diuretics in ARF for the critically ill suggests a need for a suitably powered randomised trial. PMID- 17352670 TI - The implications of enterococci for the intensive care unit. AB - OBJECTIVE: To review the evidence of pathogenicity and virulence of Enterococcus spp. in the intensive care unit. DATA SOURCES: MEDLINE search for studies and articles on Enterococcus spp. RESULTS: Enterococcus spp. are normal commensal organisms in the alimentary tract and are traditionally considered to have relatively low virulence. However, they can cause a variety of life-threatening infections, especially in immunocompromised patients and nosocomial settings. The role of enterococci as primary pathogens in polymicrobial intra-abdominal infections remains controversial. There is enough evidence to suggest that complicated, community-acquired intra-abdominal infections involving mixed flora can be treated with surgery and non-enterococcal antibiotic cover. Recent studies have shown that enterococcal peritonitis is associated with increased mortality. CONCLUSIONS: Although the prevalence of enterococcal infections may be low in Australian ICUs, these infections are associated with a higher prevalence of treatment failure and mortality. We therefore suggest the use of enterococcal antibiotic coverage in: immunocompromised patients with a high risk of bacteraemia (eg, liver transplant patients); patients with peritonitis and valvular heart disease or prosthetic intravascular material; patients with severe sepsis of abdominal origin who have previously received broad spectrum antibiotics; and patients with persistent intra- abdominal collection without clinical improvement. PMID- 17352672 TI - Statistics in review Part I: graphics, data summary and linear models. AB - Statistics and biomedical literature have historically had an uneasy alliance. A critical approach to the application of statistics is developed. Initially, we survey graphical data display and trace the historical development of the "testing" statistical paradigm, and the contributions of A R Fisher and J Neyman and E Pearson. The nuances of data summary and testing are illustrated by way of population versus sample estimation. The importance of the normality assumption is stressed, and the recurring contrast of parametric (t test) versus non parametric (Mann-Whitney) approaches to summary statistics is discussed. The t test is found to be adequate. Effect measures are outlined, and we demonstrate the utility of the unpaired t test for binary data analysis. The theory of linear models is introduced, and the underlying assumptions of the standard ordinary least squares regression are presented. The implications of transformations, in particular log transformation, are detailed, and we conclude with an overview of the principles of model selection. PMID- 17352671 TI - Extracorporeal membrane oxygenation and sepsis. AB - Extracorporeal membrane oxygenation (ECMO) is a controversial means of life support, particularly in adults. Ongoing refinements in circuit technology and widening global experience have led to ECMO being applied to a broader group of conditions than acute respiratory failure and cardiogenic shock. Septicaemia is no longer viewed as a contraindication to ECMO. Acute respiratory distress syndrome and bacterial pneumonia are the most common conditions in sepsis that may require ECMO, although septic shock with refractory hypotension may also be an indication under certain circumstances. The last indication is generally more applicable in children than adults, because of differences in the cardiovascular response to severe sepsis seen across age groups. ECMO has a role as rescue therapy in patients with severe sepsis who would otherwise die of either hypoxaemia or inadequate cardiac output. This review describes the basic technique and application of ECMO in neonates, older children, and adults with sepsis. PMID- 17352673 TI - On the very first, successful, long-term, large-scale use of IPPV. Albert Bower and V Ray Bennett: Los Angeles, 1948-1949. AB - An "unprecedented respirator patient load at Los Angeles County Hospital [LACH] in 1948 (294 respirator cases)" arose from a seasonal increase in poliomyelitis cases to nearepidemic proportions. A finding by physician Albert Bower and his team that respiratory acidosis was frequent in patients receiving intermittent negative pressure ventilation (INPV), together with their awareness of a previous high mortality rate due to the standard treatment of polio ventilatory failure with Drinker-Collins respirators, led to multiple advances in equipment technology for LACH. Most important was biomedical engineer V Ray Bennett's positive pressure respirator attachment, in use after September 1948, which converted an INPV machine, the Drinker, into one capable of supplying "intratracheal" intermittent positive pressure ventilation (IPPV), supplementary to its NPV. Together with their teams, Bower and Bennett used this attachment for 73 of 1949's 130 "respirator cases", to establish the first-ever large-scale long term success of IPPV for respiratory failure in acute polio. In 1949, they demonstrated the superiority of (supplemental) IPPV over INPV alone, achieving a survival rate of 83.7% (108/129) -- compared with the 21.1% survival rate in 1946 among the 38 patients ventilated that year. A complete system of respiratory care was developed for polio victims at LACH, setting levels of treatment and expertise distinctly higher, by 1950, than was current at other known polio respiration units, and preceding the well known developments in Copenhagen in the early 1950s. Extensive experience was obtained by a consistent medical staff, working as a team, in one hospital. Bower and Bennett deserve greater recognition of their pioneering merit than they currently receive in the written history of intensive care medicine. PMID- 17352674 TI - The definition of septic shock: implications for treatment. AB - Sepsis is among the most common reasons for admission to intensive care units throughout the world. In 1991, a new set of terms and definitions was developed to define sepsis more precisely. The concept of the "systemic inflammatory response syndrome" (SIRS) was developed, and its diagnostic criteria were defined. Sepsis was defined as suspected or microbiologically proven infection together with SIRS, while severe sepsis was defined as sepsis together with sepsis-induced organ dysfunction. Septic shock was defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation. Data from recently published trials support this hierarchical stratification, with the mortality from sepsis ranging from 10% to 15%, severe sepsis from 17% to 20%, and septic shock from 43% to 54%. The distinction between severe sepsis and septic shock is critically important as it stratifies patients into groups with a low and a high risk of dying, respectively. However, currently the diagnostic criteria of septic shock remain vague. We suggest that septic shock is best defined by a systolic blood pressure less than 90 mmHg (or a fall in systolic blood pressure of > 40 mmHg), or a mean arterial pressure less than 65 mmHg after a crystalloid fluid challenge of 30 mL per kg body weight in a patient with severe sepsis. We believe that a vasopressor should be initiated in patients who remain hypotensive after this fluid challenge. The above operational definition of septic shock is important, as it clearly and unambiguously defines in which patients, and when, treatment with a vasopressor should be initiated, and in which patients adjunctive therapy with hydrocortisone and drotrecogin alfa (activated) should be considered. PMID- 17352676 TI - Dipeptidyl peptidase IV inhibitors: the next generation of new promising therapies for the management of type 2 diabetes. AB - Type 2 diabetes is a chronic metabolic disease characterized by the presence of both fasting and postprandial hyperglycemia which is a result of pancreas beta cell dysfunction, deficiency in insulin secretion, insulin resistance and/or increased hepatic glucose production. More recently, the role of other glucoregulatory hormones, including glucagon, amylin, and the gut peptide glucagon-like peptide (GLP)-1, and an increase in the rate of postmeal carbohydrate absorption have also been included as important pathophysiologic defects. Existing anti-diabetes medications are often unefficient at achieving sustained glycemic control because they predominantly address only a single underlying defect. A number of alternative therapies for type 2 diabetes are currently under development that take advantage of the actions of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide on the pancreatic beta-cell. One such approach is based on the inhibition of dipeptidyl peptidase IV (DPP-IV), the major enzyme responsible for degrading the incretins in vivo. DPP-IV exhibits characteristics that have allowed the development of specific inhibitors with proven efficacy in improving glucose tolerance in animal models of diabetes and type 2 diabetic patients. While enhancement of insulin secretion, resulting from blockade of incretin degradation, has been proposed to be the major mode of inhibitor action, there is also evidence that inhibition of gastric emptying, reduction in glucagon secretion, peripheral insulin sensitization and important effects on beta-cell differentiation and survival can potentially preserve beta-cell mass, and improve insulin secretory function and glucose handling in diabetic patients. The present article focuses on the preclinical and clinical data of DPP-IV inhibitors that make it unique therapeutic agents representing the next generation of antidiabetes drugs. PMID- 17352677 TI - Discovery of JANUVIA (Sitagliptin), a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. AB - The emergence of glucagon-like peptide 1 (GLP-1) as a well validated approach to the treatment of type 2 diabetes and preclinical validation of dipeptidyl peptidase IV (DPP-4) inhibition as an alternate, oral approach to GLP-1 therapy prompted the initiation of a DPP-4 inhibitor program at Merck in 1999. DPP-4 inhibitors threo- and allo-isoleucyl thiazolidide were in-licensed to jump start the program; however, development was discontinued due to profound toxicity in rat and dog safety studies. The observation that both compounds inhibit the related proline peptidases DPP8 and DPP9 led to the hypothesis that inhibition of DPP8 and/or DPP9 could evoke severe toxicities in preclinical species. Indeed, the observed toxicities were recapitulated with a selective dual DPP8/9 inhibitor but not with an inhibitor selective for DPP-4. Thus, medicinal chemistry efforts focused on identifying a highly selective DPP-4 inibitor for clinical development. Initial work in an alpha-amino acid series related to isoleucyl thiazolidide was discontinued due to lack of selectivity; however, SAR studies on two screening leads led to the identification of a highly selective beta-amino acid piperazine series. In an effort to stabilize the piperazine moiety, which was extensively metabolized in vivo, a series of bicyclic derivatives were prepared, culminating in the identification of a potent and selective triazolopiperazine series. Unlike their monocyclic counterparts, these analogs typically showed excellent pharmacokinetic properties in preclinical species. Optimization of this series led to the discovery of JANUVIA (sitagliptin), a highly selective DPP-4 inhibitor for the treatment of type 2 diabetes. PMID- 17352678 TI - Aromatic heterocycle-based DPP-IV inhibitors: xanthines and related structural types. AB - Xanthines and xanthine-like DPP-IV inhibitors were first disclosed in 2002. Since then, several dozen accounts of xanthine-based DPP-IV inhibitors have been published. Only a few presentations and journal articles have appeared, with the vast majority of information coming from the patent literature. DPP-IV inhibitors related to the xanthines include purine analogues with other arrangements of the nitrogen atoms in the core structure, imidazoles, uracils, pyrimidines, pyridines, and some fused pyridines. At least one compound derived from the xanthines has advanced into clinical trials, making it likely that these molecules will play a major role in the DPP-IV inhibition arena over the next several years. PMID- 17352679 TI - 11 Years of cyanopyrrolidines as DPP-IV inhibitors. AB - Cyanopyrrolidines (cyanopyrrolidides, pyrrolidine-2-nitriles, prolinenitriles) as inhibitors of the serine protease dipeptidyl peptidase IV (DPP-IV, DP IV, CD26, EC 3.4.14.5) were first reported in 1995. The interest in this compound class grew immensely when DPP-IV was discovered as a target for the treatment of type 2 diabetes. The research on cyanopyrrolidines cumulated in the discoveries of vildagliptin (LAF237, NVP-LAF237) and saxagliptin (BMS-477118). These compounds entered Phase III clinical trials in 2004 and 2005, respectively, and an application for market approval has been filed for vildagliptin in 2006. Today cyanopyrrolidines are, as judged by the numbers of patent applications, the most prominent of several series of DPP-IV inhibitors, and have the potential to become valuable medicines for type 2 diabetes in the near future. This review summarizes some historical aspects of the discovery of cyanopyrrolidine DPP-IV inhibitors, and then focuses mainly on structure-activity-relationships, the evolution of different subseries, the possibilities to improve on the chemical instability that is associated with this compound class, and on the discoveries of vildagliptin and saxagliptin. Within this context, the properties of individual compounds and results from biological studies are discussed. The rationale of DPP-IV inhibition, clinical data, and the relevance of selectivity over related proteases are extensively reviewed in other contributions to this issue of Curr. Top. Med. Chem., and are therefore only very briefly touched. PMID- 17352680 TI - Azetidine-based inhibitors of dipeptidyl peptidase IV (DPP IV). AB - The structure-activity relationships of azetidine-based DPP IV inhibitors will be discussed in detail in the following review. The azetidine-based DPP IV inhibitors can be divided into three main subtypes, the 2-cyanoazetidines, 3 fluoroazetidines and 2-ketoazetidines. These subtypes have been explored and structure-activity relationships have been established by several groups. Several compounds within each of these subtypes display sub micromolar potency against DPP IV. The most potent cyanoazetidines and ketoazetidines have large, hydrophobic amino acid groups bound to the azetidine nitrogen and display activities below 100 nM. DPP IV inhibition is not sensitive to stereochemistry at the 2-position as both 2-(R)- and 2-(S)-cyano and -keto azetidines display similar inhibitory potencies. While these "warhead"-based cyano- and ketoazetidines have the potential for covalent, bond-forming inhibition, they can also react to internally cyclize into inactive ketopiperazines and dihydroketopyrazine. Thus, chemical instability was also explored for compounds in these two subtypes and certain members of the cyanoazetidine series display aqueous stability comparable to the closely related cyanopyrrolidines. Select 3 fluoroazetidines also display inhibitory potencies below 1 microM without the propensity for cyclization and chemical instability associated with the other subseries. PMID- 17352681 TI - Molecular recognition of ligands in dipeptidyl peptidase IV. AB - The serine protease dipeptidyl peptidase IV (DPP-IV) is a clinically validated target for the treatment of type II diabetes and has received considerable interest from the pharmaceutical industry over the last years. Concomitant with a large variety of published small molecule DPP-IV inhibitors almost twenty co crystal structures have been released to the public as of May 2006. In this review, we discuss the structural characteristics of the DPP-IV binding site and use the available X-ray information together with published structure-activity relationship data to identify the molecular interactions that are most important for tight enzyme-inhibitor binding. Optimized interactions with the two key recognition motifs, i.e. the lipophilic S1 pocket and the negatively charged Glu 205/206 pair, result in large gains in binding free energy, which can be further improved by additional favorable contacts to side chains that flank the active site. First examples show that the lessons learned from the X-ray structures can be successfully incorporated into the design of novel DPP-IV inhibitors. PMID- 17352682 TI - Prolyl peptidases related to dipeptidyl peptidase IV: potential of specific inhibitors in drug discovery. AB - Dipeptidyl peptidase IV (DPP IV) is a validated target for the treatment of type 2 diabetes, with several inhibitors currently in phase 3 clinical trials. This review will mainly focus on proline-specific dipeptidyl peptidases related to DPP IV: fibroblast activation protein (FAP), dipeptidyl peptidase 8 (DPP8), dipeptidyl peptidase 9 (DPP9) and dipeptidyl peptidase II (DPP II). The biochemical and biological properties of these enzymes will be discussed, as well as the therapeutic potential of their inhibition. The development of potent and selective inhibitors for each of these peptidases will be described. PMID- 17352684 TI - T lymphocytes as targets of statins: molecular mechanisms and therapeutic perspectives. AB - Statins are cholesterol-lowering drugs extensively used for primary and secondary prevention of cardiovascular events related to hypercholesterolemia. Because of their capacity to inhibit HMG-CoA reductase, statins also block the production of isoprenoids required for post-translational modification of proteins such as Ras superfamily GTPases, which are master regulators in signaling pathways triggered by surface receptors. As such, statins have pleiotropic effects on many cell types. In the immune system, statins harbor strong anti-inflammatory properties, which result from their capacity to interfere with the activation of proinflammatory cells, including macrophages and endothelial cells. More recently, T-lymphocytes have been identified as cellular targets of statins. Here we shall review recent findings, which document an inhibitory activity of statins on T-cell activation, proliferation, differentiation to Th1 cells and migration across the blood-brain barrier. The therapeutic perspectives of these findings, based on animal models and ongoing clinical trials, will also be discussed. PMID- 17352685 TI - Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. AB - The phosphodiesterase (PDE) 4 is the predominant cyclic AMP degrading enzyme in a variety of inflammatory cells including eosinophils, neutrophils, macrophages, T cells and monocytes. In addition, this enzyme is expressed in non-immune cells such as keratinocytes and fibroblasts. Highly selective PDE4 inhibitors are currently under evaluation for the treatment of asthma and/or chronic obstructive pulmonary disease. Due to the broad anti-inflammatory/immuno-modulatory action of PDE4 inhibitors, it has been proposed that PDE4 inhibitors might also be efficacious for skin disorders such as atopic dermatitis. Consequently, PDE4 inhibitors including cilomilast and AWD 12-281 have been tested in several models of allergic and irritant skin inflammation. These PDE4 inhibitors displayed strong anti-inflammatory action in models of allergic contact dermatitis in mice, in the arachidonic acid induced skin inflammation in mice and in ovalbumin sensitised guinea pigs. The determination of cytokines in skin homogenates revealed that both Th1 as well as Th2 cytokines are suppressed by PDE4 inhibitors, indicating an anti-inflammatory activity in both the Th2 dominated acute phase as well as the Th1 dominated chronic phase of atopic dermatitis. Due to the suppression of Th1 cytokines, activity can also be expected in psoriasis. Results of early clinical trials with both topically (cipamfylline, CP80,633) and systemically (CC-10004) active PDE4 inhibitors demonstrated efficacy in atopic dermatitis and in the case of CC-10004, also in psoriasis. AWD 12-281 (GW 842470) is currently under clinical evaluation for the topical treatment of atopic dermatitis. Results concerning clinical efficacy of this potent and selective PDE4 inhibitor are anxiously awaited. PMID- 17352686 TI - New insights on the nature of latent tuberculosis infection and its treatment. AB - Nowadays, there is no conclusive theory explaining the latent tuberculosis infection (LTBI). LTBI is reviewed herein as a standard progression of M. tuberculosis in the context of the usual microaerobiosis present in the host's tissues and displaying their main virulent factors: slow metabolism; cell wall thickness and ability to induce intragranulomatous necrosis. Therefore, latent bacilli (LB) would be generated by the irruption of specific immunity forcing bacilli to remain in a stationary phase (SP) inside the necrotic tissue. This tissue is crucial because it maintains a stable LB population and prolongs the production of foamy macrophages which facilitate the LB escape to the alveolar spaces. In the alveolar spaces, LB will regrow and, once freed in this privileged space, they will induce new granulomas -less developed because they are better controlled by immunity. This explains the ability of LB to face the chance to be drained as a consequence of the constant cellular turnover, and to survive for a long time in the lung. This activity also supports the hypothesis that generation of active TB highly depends on the probability of the LB regrowth in a favorable zone (i.e., in the pulmonary apex). This "dynamic" hypothesis faces a more classic one (or "static") essentially based on the presence of a "resuscitation" factor that would reactivate "dormant" bacilli in old lesions in the apex. Current possibilities for LTBI treatment are reviewed according to this "dynamic hypothesis", from the standard chemotherapy to the introduction of therapeutic vaccines and anti-inflammatory treatments. PMID- 17352688 TI - Biological variability and targeted delivery of therapeutics for inflammatory bowel diseases: an in silico approach. AB - Existing treatments of IBD adopt targeted oral drug delivery route for delivering bioactive agents more efficiently and with fewer side effects. However, the complex and dynamic luminal environment of the GIT and major intra/inter patient variability greatly affects treatment, resulting in variable clinical response in patients. Mathematical simulation model can be employed to consider the complex luminal environment to asses the performance of drug delivery systems for clinical efficacy. The objective of this paper was to evaluate existing targeted oral drug delivery system for the treatment of IBD subject to inter/intra patient luminal variability using in silico experiments employing previously developed mathematical model. Simulation results indicated that the average small intestinal drug release was 44+/-19% and 48+/-21% for healthy and UC subjects, respectively. The systemic absorption of drug approached 10-25% in healthy controls and 16-32% in UC subjects. Calculated drug release from the simulations for different scenario of pH and TT had a good agreement with the clinical in vivo data (13-36% and 17-35% for healthy and UC subjects, respectively). This agreement was also true for 5-ASA and its metabolite (N-acetyl-5-ASA) recovery in the colon. The computational model has a high degree of agreement with data obtained from literature. Physicians can use characteristic performance curves of different delivery systems produced in silico to select a delivery system that would work best for their patients based upon the patient's pH and transit time profiles. It also could be used by the pharmaceutical industry to improve their medicine efficacy by altering the design. PMID- 17352687 TI - Vascular remodelling and angiogenesis in asthma: morphological aspects and pharmacological modulation. AB - Tissue remodelling can affect the entire bronchial wall, including the vascular component of the mucosa, in bronchial asthma. The bronchial mucosa is more vascularized in asthmatic patients than in healthy subjects, showing an increase in the number and dimension of vessels and vascular area. In addition, vascular changes can contribute to obstructing the airway flow in asthma. Vascular Endothelial Growth Factor, a mediator derived from endothelial cells, but also from most inflammatory cells in asthma, plays a primary role in vascular remodelling and angiogenesis. Studies on lung biopsies showed that anti-asthma drugs can decrease to varying degrees the vascular component of airway remodelling in asthma. Among asthma medications, inhaled corticosteroids effectively reverse all aspects of vascular remodelling such as vasodilatation, increased vascular permeability and angiogenesis. A better knowledge of angiogenetic mechanisms in asthma will support the selection of specific medications acting on this aspect of airway remodelling. The aim of this review is to analyze the morphological aspects of the vascular component in airway remodelling in asthma, as well as its pharmacological modulation. PMID- 17352689 TI - Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammation. AB - The prevalence of allergic diseases is increasing worldwide. Hence, there is continued need for novel pharmacological therapies for the treatment of these disorders. As the mast cell is one of the essential cells that contributes to the inflammation associated with allergic diseases, this cell type remains an attractive target for such pharmacological intervention. Mast cells are major players in the early phase of the allergic response since they generate and release a variety of inflammatory mediators following antigen-dependent aggregation of IgE-bound FcepsilonRI (high affinity IgE-receptor) on the cell surface. These mediators also contribute to the late and chronic stages of allergic inflammation. Thus, the IgE/antigen response has been a major focus in the development of new drugs targeting mast cells. The essential role that stem cell factor (SCF) and its receptor, Kit, play in mast cell biology, however, may provide us with an alternative or adjunct therapy. SCF is necessary for mast cell development, proliferation and survival, but it is also known to play a role in homing and adhesion of mast cells. Furthermore, there is an increasing amount of literature demonstrating that SCF is necessary for optimal IgE/antigen-induced mast cell degranulation and cytokine production. Several drug candidates targeting SCF and/or Kit have been studied for their anti-allergic properties. These include anti-SCF antibodies, antisense oligonucleotides, Kit inhibitors, and inhibitors of downstream signaling molecules. In this review, we provide an overview of the role of SCF and Kit in mast cell activation and discuss potential drug candidates for targeting this response. PMID- 17352690 TI - Role of interleukin-21 in inflammation and allergy. AB - Interleukin-21 (IL-21) is a newly described cytokine, produced by activated CD4+ T cells. Since the discovery in 2000, IL-21 has been the object of intensive research because of its homology to IL-2, IL-4 and IL-15, and its ability to modulate both innate and adaptive immune responses. IL-21 mediates its functions through a heterodimeric receptor, composed of a specific subunit, termed IL-21 receptor (IL-21R) and the common gamma-chain, that is shared with IL-2, IL-4, IL 7, IL-9, IL-13, and IL-15 receptors. IL-21R is originally described on T, B and NK cells, which is in accordance with the cell types that mostly respond to IL 21. Indeed, IL-21 augments the proliferation of CD4+ and CD8+ T lymphocytes and regulates the profile of cytokines secreted by these cells, drives the differentiation of B cells into memory cells and terminally differentiated plasma cells, and moreover, enhances the activity of natural killer cells. More recently, IL-21R has also been documented on non-immune cells, raising the possibility that IL-21 is an important mediator in the cross-talk between immune and non-immune cells. As discussed in this review, the potential role of IL-21 in immune-mediated and allergic diseases would seem to suggest that either disrupting or enhancing IL-21 signaling may be useful in specific clinical settings. PMID- 17352691 TI - Therapeutic targeting of p-selectin in atherosclerosis. AB - P-selectin is an inflammatory adhesion molecule expressed on activated platelets and endothelial cells. The role of inflammatory cells and adhesion molecules in the development and progression of vascular diseases has been well studied in the past two decades and it is now recognised that many of the cellular and molecular events that underlie atherosclerotic vascular disease are inflammatory in nature. The critical role of P-selectin in both leukocyte recruitment and vascular disease progression has been confirmed in knockout animal models, where P selectin knockout mice crossed with apoE deficient mice exhibit significantly reduced atherosclerosis and leukocyte recruitment in the plaque. Being the primary adhesion molecule in initiating cell activation and cell adhesion to platelets and endothelial cells, P-selectin is therefore an attractive therapeutic target in vascular disease. However the basic tenet of targeting P selectin may be complicated by the presence of a soluble form of P-selectin (sP selectin). sP-selectin, lacking the cytosolic/transmembrane domain, has been identified circulating in plasma and is thought to either be derived from the secretion of an alternatively spliced protein that lacks the transmembrane domain and/or from proteolytic cleavage of the membrane form, thus reflecting the activated state of both platelets and/or endothelial cells. This review will discuss the role of P-selectin in inflammatory disease particularly in atherosclerosis and will highlight current in vitro and in vivo discoveries. PMID- 17352692 TI - Down-regulation of human RNA/DNA helicase SUV3 induces apoptosis by a caspase- and AIF-dependent pathway. AB - BACKGROUND INFORMATION: The nuclear gene hSUV3 (human SUV3) encodes an ATP dependent DNA/RNA helicase. In the yeast Saccharomyces cerevisiae the orthologous Suv3 protein is localized in mitochondria, and is a subunit of the degradosome complex which regulates RNA surveillance and turnover. In contrast, the functions of human SUV3 are not known to date. RESULTS: In the present study, we show that a fraction of human SUV3 helicase is localized in the nucleus. Using small interfering RNA gene silencing in HeLa cells, we demonstrate that down-regulation of hSUV3 results in cell cycle perturbations and in apoptosis, which is both AIF- and caspase-dependent, and proceeds with the induction of p53. CONCLUSIONS: In addition to its mitochondrial localization, human SUV3 plays an important role in the nucleus and is probably involved in chromatin maintenance. PMID- 17352693 TI - Runx3 negatively regulates Osterix expression in dental pulp cells. AB - Osterix, a zinc-finger-containing transcription factor, is required for osteoblast differentiation and bone formation. Osterix is also expressed in dental mesenchymal cells of the tooth germ. However, transcriptional regulation by Osterix in tooth development is not clear. Genetic studies in osteogenesis place Osterix downstream of Runx2 (Runt-related 2). The expression of Osterix in odontoblasts overlaps with Runx3 during terminal differentiation in vivo. Runx3 down-regulates Osterix expression in mouse DPCs (dental pulp cells). Therefore the regulatory role of Runx3 on Osterix expression in tooth development was investigated. Enforced expression of Runx3 down-regulated the activity of the Osterix promoter in the human embryonic kidney 293 cell line. When the Runx3 responsive element on the Osterix promoter, located at -713 to -707 bp (site 3, AGTGGTT) relative to the cap site, was mutated, this down-regulation was abrogated. Furthermore, electrophoretic mobility-shift assay and chromatin immunoprecipitation assays in mouse DPCs demonstrated direct functional binding of Runx3 to the Osterix promoter. These results demonstrate the transcriptional regulation of Osterix expression by Runx3 during differentiation of dental pulp cells into odontoblasts during tooth development. PMID- 17352694 TI - Developing, implementing and sustaining nursing leadership and management capacity: practical implications for quality patient services. PMID- 17352695 TI - Relevance of mission statements in Flemish not-for-profit healthcare organizations. AB - The aims of the study were to determine: (1) which components managers of Flemish not-for-profit healthcare organizations chose to incorporate in their mission statement, (2) how satisfied managers of Flemish not-for-profit healthcare organizations are with the formulation of various mission statement components and (3) if the managers of Flemish not-for-profit healthcare organizations subscribe the presumed positive relationship between mission statements and organizational performance. To address these research questions, a questionnaire was send to a convenience sample of Flemish not-for-profit healthcare managers and to a control group. The results indicate that Flemish not-for-profit healthcare managers do discriminate and differentiate between mission statement components and that they are not equally satisfied with the articulation of every component. Furthermore, Flemish not-for-profit healthcare managers do support the assumption that a well-written mission statement can produce a host of benefits. The mission statement is considered as an energy source, a guide in decision making and to influence the managers' behaviour. PMID- 17352696 TI - The need for nurses to have in service education to provide the best care for clients with chest drains. AB - Chest drains are a widespread intervention for patients admitted to acute respiratory or cardiothoracic surgery care areas. These are either inserted intraoperatively or as part of the conservative management of a respiratory illness or thoracic injury. Anecdotally there appears to be a lack of consensus among nurses on the major principles of chest drain management. Many decisions tend to be based on personal factors rather than sound clinical evidence. This inconsistency of treatment regimes, together with the lack of evidence-based nursing care, creates a general uncertainty regarding the care of patients with chest drains. This study aimed to identify the nurses' levels of knowledge with regard to chest drain management and identify and to ascertain how nurses keep informed about the developments related to the care of patients with chest drains. The data were collected using survey method. The results of the study revealed deficits in knowledge in a selected group of nurses and a paucity of resources. Nurse managers are encouraged to identify educational needs in this area, improve resources and the delivery of in service and web-based education and to encourage nurses to reflect upon their own knowledge deficits through portfolio use and ongoing professional development. PMID- 17352697 TI - The Lead Cancer Nurse - an ill-defined role? AB - The Lead Cancer Nurse (LCN) role was developed following the publication of the NHS Cancer Plan [Department of Health (2000) The NHS Cancer Plan. A Plan for Investment. A Plan for Reform. HMSO, London]. In collaboration with the Lead Cancer Clinician and Cancer Manager the role of the LCN is to contribute to the planning and delivery of cancer services in line with government guidance. However, there are significant variations in the remit and authority of the role between organizations, and limited research has been undertaken to evaluate the effectiveness of this senior nursing post. This article explores the complex and often ill-defined remit of the LCN role and compares this with Nurse Consultant and Advanced Nurse Practitioner roles. It explores the challenges that this presents both to the postholders and the organizations within which they work. Recommendations include on-going monitoring and evaluation of these posts, the development of local supportive frameworks and a review of the educational needs of these postholders. PMID- 17352698 TI - Data warehouse approach to nursing management. AB - AIM: This article describes a data warehouse approach when designing an information system to meet nursing management needs in acute hospital setting. BACKGROUND: The rapidly changing health care environment has created new challenges for nursing leaders and requires appropriate, accurate and timely data for decision-making. METHOD: Key aspects of current information needs were identified by a nursing expert group. A data warehouse-based Nursing Management Information System was produced and piloted in nine wards. A survey and interviews were conducted to evaluate the piloting. RESULTS: Data from the patient administrative system together with nursing rostering data and measures for nursing care intensity brought new opportunities for nursing management. CONCLUSIONS: A Nursing Management Information System is suggested to be built using data warehouse model. Successful implementation of a Nursing Management Information System requires systematic data quality checks. An information analyst is essential for interpreting and communicating nursing data to multi professional management groups. PMID- 17352699 TI - Challenges in delivering safe patient care: a commentary on a quality improvement initiative. AB - The specific aim of this commentary is to identify the challenges identified by nurses in the delivery of safe patient care. In reporting, some of the messages emanating from the research and policy literature, the paper highlights the importance of taking a system approach to the investigation of patient safety failures, the conflicting evidence relating to patient deaths as a result of failures in safety, and the underlying importance of culture. The paper outlines the reasons why patient safety has become so prominent, and provides a brief description of some of the definitions and terminology in current use. The commentary articulates a number of challenges in the delivery of safe care as identified by nurses during a recent quality improvement initiative, and these are organized under the themes of organizational context, working environment, and the organization and management of care. In conclusion, the paper describes the implications arising from the quality improvement initiative and the need for further research exploring the nature of safety culture in health-care organizations. PMID- 17352700 TI - Irish nurses' and midwives' understanding and experiences of empowerment. AB - AIM: This study explored conceptualizations of empowerment among Irish nurses and midwives. BACKGROUND: Current literature on the meaning of empowerment lacks consensus. As a result there is a likelihood that empowerment will be conceptualized differently between managers and subordinates. METHOD: In order to get a sense of how Irish practitioners viewed empowerment, 10 focus groups were held in locations throughout Ireland (n = 93). A national distribution of participants was obtained. RESULTS: Twenty-one different responses emerged representing what nurses and midwives understood by the term empowerment. In relation to experiences of empowerment, six themes were found to impact on empowerment experiences. Three themes emerged as central to empowerment. One theme (education for practice) was identified as an antecedent to empowerment. CONCLUSION: Empowerment is a complex concept and its meaning is contextually determined. Managers play a key role in impacting on the empowerment perceptions of Irish nurses and midwives. PMID- 17352701 TI - Computer-supported telephone nurse triage: an evaluation of medical quality and costs. AB - AIM: To evaluate a telephone nurse triage model in terms of appropriateness of referrals to the appropriate level of care, patient's compliance with given advice and costs. BACKGROUND: A key concern in each telephonic consultation is to evaluate if appropriate. METHOD: An evaluative design in primary health care with consecutive patients (N = 362) calling telephone nurse triage between November 2002 and February 2003. RESULTS: The advice was considered adequate in 325 (97.6%) cases. The patients' compliance with self-care was 81.3%, to primary health care 91.1% and to Accident and Emergency department 100%. The nurses referred self-care cases (64.7%) and Accident and Emergency cases (29.6%) from a less adequate to an appropriate level of care. The cost saving per call leading to a recommendation of self-care was euro 70.3, to primary health care euro 24.3 and to Accident and Emergency department euro 22.2. CONCLUSIONS: The telephone nurse triage model showed adequate guidance for the patients concerning level of care and released resources for the benefit of both patients and the health care system. PMID- 17352702 TI - A conceptual framework contributing to nursing administration and research. AB - The health care system has undergone major changes in the last decade. With greater acuity and complexity of illness, the adoption of innovative technologies and the shortage of health care personnel, the coordination and integration of health care services has become increasingly demanding for administrators. Growing dissatisfaction and concerns about safety issues are being expressed by the users of care who need to navigate through an increasingly complex system and by health care personnel who feel less efficient within the organization. Nursing administrators have a responsibility to address these issues but there is little scientific evidence to guide their actions. There are also few comprehensive models highlighting the main components of nursing administration - models that could guide nursing administration research. This paper presents a conceptual framework for nursing administration and research that links patient health care needs, nursing resources and the nursing care processes to the context of the health care system, and the social, political and cultural environments of care. A selected review of the oncology and cancer care literature is presented to demonstrate how this framework can organize existing knowledge about these concepts in the context of cancer care. PMID- 17352703 TI - Hospitals' organizational variables and patients' perceptions of individualized nursing care in Finland. AB - AIM: To examine the association between hospitals' organizational variables and patients' perceptions of individualized care. BACKGROUND: There is lack of evidence related to the effects that the hospital environment has on patient perceptions of the individuality of care they receive. METHODS: A cross-sectional design was used. The questionnaire survey data were obtained from 861 (response rate 82%) hospital patients and 35 (100%) nurse managers in Finland. Results An inverse relationship between the size of the hospital and ward and patients' perceptions of individualized care was found. Increased staffing or skill mix failed to predict a higher patient perception of individualized care, but primary nursing care delivery did. CONCLUSIONS: Instead of increasing the amount of nursing staff, there is a need to improve the quality of the nurse-patient interactions to facilitate individualized care. The generalizability of the study is limited by the regional nature of the setting. PMID- 17352704 TI - How nursing leadership and management interventions could facilitate the effective use of ICT by student nurses. AB - AIM: This article makes the case for how evidence-based nursing leadership and management activities could promote, implement and sustain quality patient care by student nurses using Information and Communications Technology. It is on aspects of the findings of a professional doctorate inquiry into Information and Communications Technology use and skills development by student nurses. BACKGROUND: The 21st century is both an information and knowledge age. Nursing and medical professions are facing the increasing usage of information technology in day-to-day operations with the overall aim of improving the quality of patient care. The quality of the future of the nursing profession is dependent on the calibre of those who are currently socialized to become professional nurses. The new United Kingdom Labour Government, in power since 1997, has placed increasing focus on the effectiveness of the National Health Service and using computers as one way to assist in achieving greater effectiveness. This has implications for nurse education and the future preparation of future nurses to acquire skills in Information and Communications Technology. METHOD: This is a case study approach using multiple triangulation methodology. This includes: semi-structured interview of six student nurses and four of their mentors; one unstructured meeting with the Research and Development Manager; observational visit to a medical admission ward and a renal unit; one semi-structured meeting with the Information Manager; Review of Documentation - the National Health Service Trust Nursing Strategy; and Review, Application and Development of relevant theory. FINDINGS: The overall findings are that student nurses are not using Information and Communications Technology in nursing practice in a structured and systematic way. The reasons for this are very many and very complex but are interrelated. They include strategic resource-based issues, what Jumaa referred to as Time, Human, Equipment, Information, Material and Money resources. These reasons include lack of time for Information and Communications Technology activities by both students and the qualified nurses and some staff with poor Information and Communications Technology skills. This situation is compounded by insufficient computer hardware; lack of information about the essence and value of Information and Communications Technology; perception of the direct relevance of Information and Communications Technology activities to patient care; software materials not adequate for purpose and lack of comprehensive budget and financial recognition for student's engagement with Information and Communications Technology. CONCLUSION: 'Smile and the whole world smile with you'. This old saying has a lot of truth in it. Applied to Information and Communications Technology skills development and use by student nurses we are confronted with an uncomfortable reality of many qualified nurses who themselves are not comfortable or proficient with the use of Information and Communications Technology. Some do not see the essential need for Information and Communications Technology and its direct relevance to improving patient care, nor is this always supported by the current software and systems. Willmer argued that the achievement of effective implementation of the National Health Service National Programme for Information and Technology requires efficient change management and leading people skills, and an understanding of National Health Service culture. In this article the case is made that evidence-based management and leadership interventions are a feasible approach for a sustained implementation of Information and Communications Technology use and skills development by student nurses. PMID- 17352705 TI - Care-planning meetings with stroke survivors: nurses as moderators of the communication. AB - INTRODUCTION: Stroke survivors often have communicative disabilities. They should, however, be involved when decisions are made about their care treatment. AIM: To explore and describe how nurses act as moderators of the communication in cooperative care-planning meetings and what kind of participant status the patients achieve in this type of multi-party talk. METHOD: Thirteen care-planning meetings were audio-recorded and transcribed. Nurses, social workers and stroke survivors were the main participants for the meetings. A coding scheme was created and three main categories were used for the analysis: pure utterance types, expert comments (EC) and asymmetries. RESULTS: The nurses never invited the patients to tell their own versions without possible influence from them. Mostly the nurses gave ECs. The nurses acted as the patients' advocates by talking for or about them. They rarely supported the patients' utterances. CONCLUSION: There is an urgent need for nurses to learn how to involve the patients in the communicative process about their treatment. Assessment of the patients' communicative abilities before the care-planning meetings as well as knowledge about how to invite them can improve the patients' participant status. PMID- 17352706 TI - Frail older people's experiences and use of health and social care services. AB - AIMS: To highlight older people's experiences and expectations of services and the consequences for service provision, service development and research. RATIONALE: A large amount of resources have been invested in providing services for frail older people who experienced multiple hospital admissions. However, their own views are under-reported. METHOD: Semi-structured interviews with frail older people were conducted in four Scottish Health Board areas to explore the context of emergency admissions and the use of extramural services. OUTCOMES: Frail older people are high users of services but claim that services are not responsive to their main concerns: meeting individual needs, maximizing independence and helping to live fulfilled lives. Services not catering for these needs are often cancelled or left in abeyance. CONCLUSION: The same people who are targeted by care services are reluctant to engage with them. Care providers need to adopt older people's priorities to provide them with responsive patient centred care. PMID- 17352707 TI - Building the capacity for evidence-based clinical nursing leadership: the role of executive co-coaching and group clinical supervision for quality patient services. AB - AIM: The general aims of this article were to facilitate primary care nurses (District Nurse Team Leaders) to link management and leadership theories with clinical practice and to improve the quality of the service provided to their patients. The specific aim was to identify, create and evaluate effective processes for collaborative working so that the nurses' capacity for clinical decision-making could be improved. BACKGROUND: This article, part of a doctoral study on Clinical Leadership in Nursing, has wider application in the workplace of the future where professional standards based on collaboration will be more critical in a world of work that will be increasingly complex and uncertain. This article heralds the type of research and development activities that the nursing and midwifery professions should give premier attention to, particularly given the recent developments within the National Health Service in the United Kingdom. The implications of: Agenda for Change, the Knowledge and Skills Framework, 'Our Health, Our Care, Our Say' and the recent proposals from the article 'Modernising Nursing Career', to name but a few, are the key influences impacting on and demanding new ways of clinical supervision for nurses and midwives to improve the quality of patient management and services. METHOD: The overall approach was based on an action research using a collaborative enquiry within a case study. This was facilitated by a process of executive co-coaching for focused group clinical supervision sessions involving six district nurses as co-researchers and two professional doctoral candidates as the main researchers. The enquiry conducted over a period of two and a half years used evidence-based management and leadership interventions to assist the participants to develop 'actionable knowledge'. Group clinical supervision was not practised in this study as a form of 'therapy' but as a focus for the development of actionable knowledge, knowledge needed for effective clinical management and leadership in the workplace. FINDINGS: 1. Management and leadership interventions and approaches have significantly influenced the participants' capacity to improve the quality of services provided to their patients. 2. Using various techniques, tools, methods and frameworks presented at the sessions increased participants' confidence to perform. 3. A structured approach like the Clinical Nursing Leadership Learning and Action Process (CLINLAP) model makes implementing change more practical and manageable within a turbulent care environment. The process of Stakeholder Mapping and Management made getting agreement to do things differently much easier. Generally it is clear that many nurses and midwives, according to the participants, have to carry out management and leadership activities in their day-to-day practice. The traditional boundary between the private, the public and the voluntary sector management is increasingly becoming blurred. CONCLUSION: It is conclusive that the district nurses on this innovative programme demonstrated how they were making sense of patterns from the past, planning for the future and facilitating the clinical nursing leadership processes today to improve quality patient services tomorrow. Their improved capacity to manage change and lead people was demonstrated, for example, through their questioning attitudes about the dominance of general practitioners. They did this, for example, by initiating and leading case conferences with the multi disciplinary teams. It became evident from this study that to use group clinical supervision with an executive co-coaching approach for the implementation and to sustain quality service demand that 'good nursing' is accepted as being synonymous with 'good management'. This is the future of 'new nursing'. PMID- 17352708 TI - Evolution of sex chromosomes: dosage compensation of the Lcp1-4 gene cluster on the evolving neo-X chromosome in Drosophila miranda. AB - In Drosophila miranda the small multigene family of the larval cuticle protein (Lcp1-4) genes resides on the evolving neo-X and neo-Y sex chromosome pair while in the sibling species Drosophila pseudoobscura and Drosophila persimilis the gene cluster is inherited autosomally. The neo-Y chromosomal Lcp1, Lcp2 and Lcp4 genes are, as previously shown by us, not expressed and only Lcp3 is expressed at a strongly reduced level. As a first step in understanding the evolutionary mechanism(s) transforming an autosome into a dosage compensated X we analysed the expression behaviour and promoter structure of the Lcp1-4 genes on the neo-X. The normalized relative expression levels reveal that all four neo-X chromosomal Lcp genes in D. miranda males, including Lcp3, are already dosage compensated. PMID- 17352709 TI - Organ donation: the gift, the weight and the tyranny of good acts. PMID- 17352710 TI - Banff '05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN'). AB - The 8th Banff Conference on Allograft Pathology was held in Edmonton, Canada, 15 21 July 2005. Major outcomes included the elimination of the non-specific term "chronic allograft nephropathy" (CAN) from the Banff classification for kidney allograft pathology, and the recognition of the entity of chronic antibody mediated rejection. Participation of B cells in allograft rejection and genomics markers of rejection were also major subjects addressed by the conference. PMID- 17352711 TI - Donation after cardiac death kidneys with low severity pre-arrest acute renal failure. AB - The widening gap between supply and demand for renal transplantation has prompted many centers to use donors after cardiac death. Some of these donors exhibit signs of acute renal failure (ARF) prior to cardiac arrest. Concern has been expressed about poor quality of graft function from such donors. In response to this perception, we reviewed 49 single renal transplant recipients from category III donors after cardiac death between 1998 and 2005, at our center. All kidneys but one had hypothermic machine perfusion and viability testing prior to transplantation. According to the RIFLE criteria, nine recipients had kidneys from donors with "low severity pre-arrest ARF". The remainder of the recipients were used as control group. There was no statistical significant difference in delayed graft function and rejection rates between these two groups. Recipients GFR at 12 months was 44.4 +/- 17.1 and 45.2 +/- 14.7 (mL/min/1.73m(2)) from donors with ARF and without ARF, respectively (p = 0.96). In conclusion, low severity ARF in kidneys from controlled after cardiac death donors can be a reversible condition after transplantation. Short-term results are comparable to the kidneys from same category donors without renal failure, providing that some form of viability assessment is implemented prior to transplantation. PMID- 17352712 TI - Pretransplant risk assessment in renal allograft recipients using virtual crossmatching. AB - Preformed donor-specific HLA-antibodies antibodies (DSA) are a major risk for early antibody-mediated rejection (AMR). This prospective study evaluated the accuracy of pretransplant risk assessment using virtual crossmatching (virtualXM) (i.e. comparing HLA-typing of the donor with the recipient's HLA-antibody specificities determined by flow-beads). Sixty-five consecutive patients were stratified according to virtualXM results: patients without DSA (n= 56) were considered low risk and received standard immunosuppression; patients with DSA (n= 9) were considered high risk and received additional induction with anti-T lymphocyte-globulin (ATG) and intravenous immunoglobulins. Despite induction therapy 4 of 9 patients with DSA (44%) had clinical/subclinical AMR, whereas only 2 of 56 patients without DSA (4%) (p = 0.002). Notably, one of these two patients had early AMR likely induced by non-HLA-antibodies; the other had subclinical AMR at month 6 consistent with de novo DSA. The results of virtualXM and retrospectively obtained flow-cytometric crossmatches (FCXM) (n= 59) were concordant in 51 patients (86%), four patients (7%) were virtualXM-/FCXM+ and none had AMR, four patients (7%) were virtualXM+/FCXM- and one had AMR. VirtualXM can accurately define absence or presence of DSA and may become an invaluable tool for organ allocation and pretransplant risk assessment. However, further studies need to address whether all HLA-antibodies detected by flow-beads are clinically relevant. PMID- 17352713 TI - C4d and C3d staining in biopsies of ABO- and HLA-incompatible renal allografts: correlation with histologic findings. PMID- 17352715 TI - Impact of recipient age on the long-term outcome of living donor liver transplantation for post-kasai biliary atresia. PMID- 17352718 TI - Treatment of pigmented lesions of neurofibromatosis 1 with intense pulsed-radio frequency in combination with topical application of vitamin D3 ointment. AB - Cafe-au-lait spots and pigmented freckling are found in most of patients with neurofibromatosis 1 (NF1). Although many modalities have been used for treating the pigmented lesions, the response to treatment has been variable. Therefore, we performed the treatment of pigmented lesions with NF1 by intense pulsed-radio frequency (IPL-RF) in combination with topical application of vitamin D(3) ointment. Eight patients were treated in this study and the improvement was moderate to good in six cases (75%) although the response was relatively mild. Thus, results from our study indicate that IPL-RF irradiation in combination with topical application of vitamin D(3) ointment would be useful as new modalities, especially for treatment of numerous small pigmented lesions in patients with NF1. Although further studies with large groups of patients should be performed for a better conclusion, it could improve quality of life with NF1 patients who are concerned with serious cosmetic and social problems. PMID- 17352719 TI - Blood concentrations, tolerability and efficacy of pimecrolimus cream 1% in Japanese infants and children with atopic dermatitis. AB - Pimecrolimus cream 1% is a topical calcineurin inhibitor for the treatment of atopic dermatitis. Minimal systemic exposure to pimecrolimus has been previously observed in Caucasian pediatric patients treated with the cream twice daily for up to 1 year. The objective of this open-label, non-comparative, multicenter study was to assess the systemic exposure, tolerability and efficacy of pimecrolimus cream 1% when used twice daily for 3 weeks in pediatric patients of Japanese background. The patient cohort consisted of 17 Japanese infants and children (age range, 3.6 months to 11.6 years) with atopic dermatitis of at least mild severity affecting >or=10% of the total body surface area (range, 10-48%). Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood levels of pimecrolimus were determined on days 1, 10 and 22. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, physical condition and vital signs. Efficacy parameters included the Eczema Area and Severity Index, the Investigators' Global Assessment and the pruritus score. The median exposure to pimecrolimus cream 1% was 22 treatment days (range, 9-29 treatment days). Pimecrolimus blood concentrations were <0.5 ng/mL in 94% of samples on day 1, in 93% of samples on day 10 and in 100% of samples on day 22, with no indication of an increase with increasing body surface area treated (up to 48% of the total body surface area). No drug-related systemic adverse events or serious adverse events were reported. Treatment was effective according to all efficacy parameters. The findings of this study indicate that the use of pimecrolimus cream 1% results in minimal systemic absorption of the active ingredient in pediatric patients of Japanese background with extensive disease. PMID- 17352720 TI - Treatment of idiopathic prurigo nodularis in Taiwanese patients with low-dose thalidomide. AB - Prurigo nodularis is an intensely pruritic dermatosis characterized by lichenified and excoriated papules and nodules. The course of prurigo nodularis is often chronic, and some patients respond very poorly to the standard therapeutic modalities. Because the pathogenesis of this disease remains obscure, the treatment of prurigo nodularis can be disappointing and frustrating for both the patients and physicians. Thalidomide, a tumor necrosis factor-alpha antagonist, has been suggested as an alternative treatment option for recalcitrant prurigo nodularis. In the past, the regimen for treatment of prurigo nodularis often required thalidomide at 200 mg/day. We recruited patients with intractable prurigo nodularis and treated them with low-dose thalidomide. Six patients with idiopathic prurigo nodularis were successfully treated with low dose thalidomide (50-100 mg/day) without clinical development of peripheral neuropathy. In summary, our preliminary results suggest that low-dose thalidomide may be a safe and effective treatment option for patients with recalcitrant idiopathic prurigo nodularis. PMID- 17352721 TI - Neutrophilic dermatosis of the hands: presentation of eight cases and review of the literature. AB - Pustular dermatosis of the dorsal hands is a peculiar variant of Sweet's syndrome described by Strutton et al. Nevertheless, not all authors accept this entity. We present a retrospective study of eight cases of neutrophilic vasculitis of the hands. Three patients presented with lesions only on the dorsal hands, three with lesions on the palmar surface and two with lesions on the dorsal and palmar surfaces of the hands. The patients with lesions on the dorsal surface presented a pustular aspect, and the histopathological examination revealed a high degree of vascular damage with presence of vasculitis and, in one case, with fibrinoid necrosis. Therefore, the term pustular vasculitis of the dorsal hands introduced by Strutton et al. should probably be conserved. Our cases may have demonstrated a peculiar clinicopathological disease with its own entity. PMID- 17352722 TI - Laboratory-based epidemiological study of superficial fungal infections. AB - Dermatophytosis continues to be a worldwide problem, constituting a large bulk of cases attending the dermatology outpatient's department in tropical countries. Variable climatic conditions and multiple etiological agents, whose individual prevalence varies with time, prompted an attempt to define the current pattern and etiologic prevalence in our locality, and compare them with earlier studies from different centers. Of consenting patients clinically diagnosed to have superficial fungal infections, 1975 were investigated in the laboratory. All the specimens collected from patient skin, hair or nails were subjected to direct microscopy examination in 10% potassium hydroxide (KOH) and fungal culture. Confirmed diagnosis was made only if specimen was KOH and/or culture positive. Male : female ratio was 1.65 : 1. Tinea corporis (21.4%), onychomycoses (14.7%) and tinea capitis (6.2%) were the most common laboratory-confirmed infections. Only 909 patients (47%) out of 1035 clinically suspected patients had evidence of fungal infection by either microscopy and/or culture. Of these 909 patients, 787 (86.5%) were both KOH and culture positive, 25 (2.7%) were KOH negative and culture positive, while 97 (10.6%) were KOH positive but culture negative. In 1051 patients (53%), no evidence of fungal infection was seen. Trichophyton rubrum was the most commonly isolated dermatophyte (55.2%) followed by Trichophyton mentagrophytes (19.6%) and Trichophyton tonsurans (2.9%). Candida sp. accounted for 16% of all isolates. Non-dermatophyte moulds (NDM) were isolated only in patients with onychomycoses. Our study revealed a male preponderance, tinea corporis as the commonest clinical type, and dermatophytes as the commonest mycological isolates, which is in agreement with earlier studies. Relying on clinical diagnosis alone without laboratory confirmation may result in overestimation of the problem as evidenced in other studies as compared to our study. Rarely reported NDM appear to be important etiological agents of onychomycoses. PMID- 17352723 TI - Expression of CCR5 in graft-versus-host disease (GVHD) of the skin: immunohistochemical staining of 38 cases. AB - To ascertain the involvement of CCR5 in prolongation of graft-versus-host disease (GVHD), we performed immunohistochemical staining of CCR5 in 38 GVHD samples (23 acute and 15 chronic). A total of seven out of 15 cases of chronic GVHD were positive for CCR5; however, only two out of 23 in acute GVHD were positive for CCR5. In three cases, expression of CCR5 in infiltrating lymphocytes was negative in the acute phase, but positive in the chronic phase of GVHD. These findings suggest that the immunopathological mechanism that differentiates between acute and chronic GVHD is a CCR5-mediated immunoreaction. PMID- 17352724 TI - Sweet's syndrome associated with skin methicillin-resistant Staphylococcus epidermidis infection. AB - A 53-year-old Chinese man presented with fever, a painful exudative plaque around his left eye and subsequent multiple tender plaques and nodules on his bilateral face, neck and back. He had a 12-year history of refractory anemia, a subtype of myelodysplastic syndrome. Repeated bacterial cultures of exudates from the lesion of the left zygomatic area showed growth of methicillin-resistant Staphylococcus epidermidis. A biopsy of a plaque on the back showed edema of the papillary dermis and marked neutrophilic infiltrates in the upper dermis. The patient was diagnosed with Sweet's syndrome (SS), and responded well to combination therapy of amoxycilline/sulbactam and corticosteroids. To our knowledge, this is the first reported case of SS associated with skin S. epidermidis infection. PMID- 17352725 TI - Nuchal fibroma presenting as two posterior neck masses. PMID- 17352726 TI - Successful treatment of refractory warts with topical vitamin D3 derivative (maxacalcitol, 1alpha, 25-dihydroxy-22-oxacalcitriol) in 17 patients. PMID- 17352727 TI - Multiple scrotal epidermolytic acanthomas successfully treated with topical imiquimod. PMID- 17352728 TI - Scleredema adultorum treated with narrow-band ultraviolet B phototherapy. PMID- 17352729 TI - Case of balanitis circumscripta plasmacellularis. PMID- 17352730 TI - Adult case of Langerhans cell histiocytosis. PMID- 17352731 TI - Coexistence of disseminated primary anetoderma and generalized granuloma annulare like papules. PMID- 17352732 TI - Herpes simplex virus in association with lip leucoderma. PMID- 17352733 TI - Bleeding tendency and disease activity in Henoch-Schonlein purpura: comment. PMID- 17352734 TI - A comparative proteome analysis of human metaphase chromosomes isolated from two different cell lines reveals a set of conserved chromosome-associated proteins. AB - A comparative proteome analysis of human metaphase chromosomes between a typical epithelial-like cell, HeLa S3, and a lymphoma-type cell, BALL-1, was performed. One-dimensional (1-D) SDS-PAGE and radical-free and highly reducing two dimensional electrophoresis (RFHR 2-DE) detected more than 200 proteins from chromosomes isolated from HeLa S3 cells, among which 189 proteins were identified by mass spectrometry (MS). Consistent with our recent four-layer structural model of a metaphase chromosome, all the identified proteins were grouped into four distinct levels of abundance. Both HeLa S3 and BALL-1 chromosomes contained specific sets of abundant chromosome structural and peripheral proteins in addition to less abundant chromosome coating proteins (CCPs). Furthermore, titin array analysis and a proteome analysis of the ultra-high molecular mass region indicated an absence of titin with their molecular weight (MW) more than 1000 kDa. Consequently, the present proteome analyses together with previous information on chromosome proteins provide the comprehensive list of proteins essential for the metaphase chromosome architecture. PMID- 17352735 TI - Cytoplasmic splicing of tRNA in Saccharomyces cerevisiae. AB - The splicing of nuclear encoded RNAs, including tRNAs, has been widely believed to occur in the nucleus. However, we recently found that one of the tRNA splicing enzymes, splicing endonuclease, is localized to the outer surface of mitochondria in Saccharomyces cerevisiae. These results suggested the unexpected possibility of tRNA splicing in the cytoplasm. To investigate this possibility, we examined whether cytoplasmic pre-tRNAs are bona fide intermediates for tRNA maturation in vivo. We isolated a new reversible allele of temperature-sensitive (ts) sen2 (HA sen2-42), which encodes a mutant form of one of the catalytic subunits of yeast splicing endonuclease. The HA-sen2-42 cells accumulated large amounts of pre tRNAs in the cytoplasm at a restrictive temperature, but the pre-tRNAs were diminished when the cells were transferred to a permissive temperature. Using pulse-chase/hybrid-precipitation techniques, we showed that the pre-tRNAs were not degraded but rather converted into mature tRNAs during incubation at the permissive temperature. These and other results indicate that, in S. cerevisiae, pre-tRNAs in the cytoplasm are genuine substrates for splicing, and that the splicing is indeed carried out in the cytoplasm. PMID- 17352736 TI - A requirement of FancL and FancD2 monoubiquitination in DNA repair. AB - The rare hereditary disorder Fanconi anemia (FA) can be caused by mutations in components of the FA core complex (FancA/B/C/E/F/G/L/M), a key regulator FancD2, the breast cancer susceptibility protein BRCA2/FancD1, or the newly identified FancJ/BRIP1 helicase. By performing yeast two-hybrid (Y2H) screens using N terminal chicken (ch) FancD2 as a bait, we have identified chFancL, the likely ubiquitin E3 ligase subunit of the FA core complex. We also found that ectopically expressed FancD2 and FancL co-immunoprecipitated in 293T cells, and this interaction was dependent on the PHD domain of FancL. FANCL-disrupted chicken DT40 cells displayed defects in both FancD2 monoubiquitination and focus formation. Importantly, cell lines lacking the FANCL or FANCD2 genes, or carrying a "knock-in" mutation of the FancD2 monoubiquitination site (where the Lys 563 residue is changed to Arg), displayed quantitatively identical defects in the repair of I-SceI-induced chromosomal breaks by homologous recombination (HR). These data establish the role of FANCL and FancD2 monoubiquitination in HR repair. PMID- 17352737 TI - The fission yeast DASH complex is essential for satisfying the spindle assembly checkpoint induced by defects in the inner-kinetochore proteins. AB - Spindle assembly checkpoint (SAC) is an evolutionarily conserved surveillance system for chromosome missegregation. We isolated fission yeast Hos2, a component of the Dam1/DASH complex, as a multicopy suppressor of temperature-sensitive (ts) growth of nnf1-495 mutant that exhibits the minichromosome instability (mis) phenotype, producing lethal aneuploids without prominent mitotic delay. It remains elusive why SAC is satisfied in mis mutants despite the occurrence of missegregation. We found that Hos2 binds to the inner-kinetochore regions in both prometaphase and metaphase. Hos2 is essential for kinetochore localization of Dis1, a microtubule (MT) associated Dis1/XMAP215/TOG family protein that is required for proper MT dynamics. Cells lacking DASH exhibit cold-sensitive (cs) growth with the defective in sister-chromatid disjoining (dis) phenotype, which is characterized by hyper-condensed sister-chromatid pairs and elongated spindle MTs. Although DASH-deficient cells are viable at high temperatures, DASH-deletion transforms all the inner-kinetochore mis mutants so far tested into a constitutively active state of SAC, leading to the dis phenotype. We also discovered that Hos2 over-expression commonly suppresses growth retardation in a variety of inner-kinetochore mutants. These genetic interactions highlight the DASH-action(s) in satisfying SAC when aneuploids are formed during mitosis in the inner-kinetochore-defective mis mutants. PMID- 17352738 TI - Meltrin beta (ADAM19) mediates ectodomain shedding of Neuregulin beta1 in the Golgi apparatus: fluorescence correlation spectroscopic observation of the dynamics of ectodomain shedding in living cells. AB - Membrane-anchored Neuregulin beta1 sheds its ectodomain as soluble factors. Two proteases that belong to a disintegrin and metalloprotease (ADAM) family are known to cleave Neuregulin beta1. One is tumor necrosis factor-alpha converting enzyme (TACE/ADAM17). The other is Meltrin beta (ADAM19). Against our expectation that shedding by ADAM proteases occurs at the cell surface, here we found that Meltrin beta mediates the ectodomain shedding of Neuregulin beta1 in the Golgi apparatus. Meltrin beta was localized in and around the Golgi apparatus in developing sensory neurons. Subcellular fractionation revealed that Meltrin beta generated soluble Neuregulin beta1 in Golgi-enriched fractions while TACE-cleaved Neuregulin beta1 was recovered in lighter fractions. To examine whether Meltrin beta-mediated ectodomain shedding occurs in the Golgi apparatus in living cells, we took advantage of different diffusion properties of cleavage products from those of membrane-anchored precursor proteins. Fluorescence correlation spectroscopy (FCS) is the most sensitive method to determine milli approximately submillisecond diffusion in vivo. Protease-active Meltrin beta caused a shift in autocorrelation function in FCS of green fluorescent protein (GFP)-tagged Neuregulin beta1 in the Golgi apparatus, suggesting a conversion of Neuregulin beta1 molecules from membrane-anchored to soluble forms in that organelle. The Golgi apparatus is a site of processing Neuregulin beta1 by Meltrin beta. PMID- 17352739 TI - Regulation of platelet-derived growth factor-induced Ras signaling by poliovirus receptor Necl-5 and negative growth regulator Sprouty2. AB - Necl-5, known as a poliovirus receptor and up-regulated in many cancer cells, enhances platelet-derived growth factor (PDGF)-induced activation of Ras-Raf-MEK ERK signaling, but not PDGF-induced tyrosine phosphorylation of PDGF receptor, resulting in facilitation of cell proliferation. Here, we showed that Necl-5 interacted with Sprouty2, known to be a negative regulator of growth factor induced signaling, and reduced the inhibitory effect of Sprouty2 on PDGF-induced Ras signaling. Necl-5 was reported to be down-regulated by its trans-interaction with nectin-3 upon cell-cell contact, initiating cooperative cell-cell adhesion with cadherin. This down-regulation of Necl-5 caused tyrosine phosphorylation of Sprouty2 by c-Src, which was activated by PDGF receptor in response to PDGF, and inhibited PDGF-induced Ras signaling. Thus, Necl-5 and Sprouty2 cooperatively regulate PDGF-induced Ras signaling. The roles of Necl-5 and Sprouty2 in contact inhibition for cell proliferation are also discussed. PMID- 17352740 TI - HDAC2 controls IgM H- and L-chain gene expressions via EBF1, Pax5, Ikaros, Aiolos and E2A gene expressions. AB - We previously reported that histone deacetylase-2 (HDAC2) controls the amount of IgM H-chain at the steps of transcription of its gene and alternative processing of its pre-mRNA in DT40 cells. Here, we showed not only that the HDAC2-deficiency caused repressions of gene expressions for HDAC7, EBF1, Pax5, Aiolos and Ikaros, and elevations of gene expressions for HDAC4, HDAC5, PCAF and E2A, but also that it caused altered acetylation levels of several Lys residues of core histones. Using gene targeting techniques, we generated three homozygous DT40 mutants: EBF1(-/-), Aiolos(-/-) and E2A(-/-), devoid of EBF1, Aiolos and E2A genes, respectively. Semiquantitative RT-PCR analysis of the resultant mutants revealed not only that EBF1 and Aiolos down-regulate expressions of IgM H- and L-chain genes, but also that E2A up-regulates expressions of these two genes. These results, together with others, indicate that HDAC2 controls indirectly expressions of IgM H- and L-chain genes through opposite transcriptional regulations of EBF1, Pax5, Aiolos plus Ikaros and E2A genes. PMID- 17352741 TI - c-Ski activates MyoD in the nucleus of myoblastic cells through suppression of histone deacetylases. AB - c-Ski, originally identified as an oncogene product, induces myogenic differentiation in nonmyogenic fibroblasts through transcriptional activation of muscle regulatory factors. Although c-Ski does not bind to DNA directly, it binds to DNA through interaction with Smad proteins and regulates signaling activities of transforming growth factor-beta (TGF-beta). In the present study, we show that c-Ski activates the myogenin promoter independently of regulation of endogenous TGF-beta signaling. Expression of myogenin is regulated by a transcription factor complex containing proteins of the MyoD family and the myocyte enhancer factor 2 (MEF2) family. c-Ski acts on the MyoD-MEF2 complex and modulates the activity of MyoD in myogenin promoter regulation. Interestingly, histone deacetylase (HDAC) inhibitors up-regulated basal activity of transcription from a MyoD-responsive reporter, although c-Ski failed to further augment this transcription in the presence of HDAC inhibitors. c-Ski is observed both in the cytoplasm and in the nucleus, but its nuclear localization is required for myogenic differentiation. We conclude that c-Ski induces myogenic differentiation through acting on MyoD and inhibiting HDAC activity in the nucleus of myogenic cells. PMID- 17352742 TI - Epigenetic regulation of Nanog gene in embryonic stem and trophoblast stem cells. AB - The Nanog and Oct-4 genes are essential for maintaining pluripotency of embryonic stem (ES) cells and early embryos. We previously reported that DNA methylation and chromatin remodeling underlie the cell type-specific mechanism of Oct-4 gene expression. In the present study, we found that there is a tissue-dependent and differentially methylated region (T-DMR) in the Nanog up-stream region. The T-DMR is hypomethylated in ES cells, but is heavily methylated in trophoblast stem (TS) cells and NIH/3T3 cells, in which the Nanog gene is repressed. Furthermore, in vitro methylation of T-DMR suppressed Nanog promoter activity in reporter assay. Chromatin immunoprecipitation assay revealed that histone H3 and H4 are highly acetylated, and H3 lysine (K) 4 is hypermethylated at the Nanog locus in ES cells. Conversely, histone deacetylation and H3-K4 demethylation occurred in TS cells. Importantly, in TS cells, hypermethylation of H3-K9 and -K27 is found only at the Nanog locus, not the Oct-4 locus, indicating that the combination of histone modifications associated with the Nanog gene is distinct from that of the Oct-4 gene. In conclusion, the Nanog gene is regulated by epigenetic mechanisms involving DNA methylation and histone modifications. PMID- 17352743 TI - Accumulation of multiple forms of lamin A with down-regulation of FACE-1 suppresses growth in senescent human cells. AB - 5-Bromodeoxyuridine (BrdU) clearly induces a senescence-like phenomenon in every cell type. Proteome analysis revealed that lamin A and C were most highly increased in the nuclei of HeLa cells upon addition of BrdU. Immunoblot analysis also revealed marked accumulation of nuclear prelamin A. Consistently, farnesylated-proteins converting enzyme 1 (FACE-1) was markedly down-regulated in the same cells. Similar phenomena were also observed in normal human fibroblasts undergoing replicative senescence. Immunochemical analysis confirmed the above results. Lamin A is a major component of lamina and responsible for several genetic diseases. Thus, we ectopically expressed a wild-type, a mature type and a premature type of lamin in HeLa cells. All of these forms similarly inhibited colony formation and delayed cell cycle progression mainly through G2 phase. These results suggest that a change in the amount of lamin A, rather than appearance of its truncated form, is responsible for growth retardation in affected cells. PMID- 17352744 TI - The adaptor-like protein ROG-1 is required for activation of the Ras-MAP kinase pathway and meiotic cell cycle progression in Caenorhabditis elegans. AB - The Ras-MAP kinase pathway regulates varieties of fundamental cellular events. In Caenorhabditis elegans, this pathway is required for oocyte development; however, the nature of its up-stream regulators has remained elusive. Here, we identified a C. elegans gene, rog-1, which encodes the only protein having the IRS-type phosphotyrosine-binding (PTB) domain in the worms. ROG-1 has no obvious domain structure aside from the PTB domain, suggesting that it could serve as an adaptor down-stream of protein-tyrosine kinases (PTKs). RNA interference (RNAi)-mediated down-regulation of rog-1 mRNA significantly decreased brood size. rog-1(tm1031) truncation mutants showed a severe disruption in progression of developing oocytes from pachytene to diakinesis, as was seen in worms carrying a loss-of function mutation in the let-60 Ras or mpk-1 MAP kinase gene. Furthermore, let-60 Ras-regulated activation of MPK-1 in the gonad is undetectable in rog-1(tm1031) mutants. Conversely, a gain-of-function mutation in the let-60 Ras gene rescues the brood size reduction and germ cell abnormality in rog-1(tm1031) worms. Consistently, rog-1 is preferentially expressed in the germ cells and its expression in the gonad is essential for oocyte development. Thus, ROG-1 is a key positive regulator of the Ras-MAP kinase pathway that permits germ cells to exit from pachytene. PMID- 17352745 TI - Recruitment of CG-NAP to the Golgi apparatus through interaction with dynein dynactin complex. AB - The structural organization and position of the Golgi apparatus are highly regulated by microtubule cytoskeleton and microtubule motor proteins. The mechanisms linking these proteins to the Golgi apparatus remain elusive. Here, we found that centrosome and Golgi-localized PKN associated protein (CG-NAP) was localized to the Golgi apparatus in a microtubule-dependent manner. Microtubule binding experiments revealed that CG-NAP possessed two microtubule-binding domains. We also found that CG-NAP was well co-localized with cytoplasmic dynein subunits during recovery from the on-ice treatment of cells that induced dissociation of CG-NAP from the Golgi. Similar co-localization was observed during recovery from the acetate treatment, which has been reported to inhibit the dynein-mediated transport. CG-NAP was co-immunoprecipitated with a dynactin subunit p150(Glued). Expressing the p150(Glued)-binding region of CG-NAP fused with mitochondria-targeting sequence induced recruitment of mitochondria to the pericentriolar area, suggesting that this region interacts with functional cytoplasmic dynein in vivo. Moreover, over-expression of this region caused fragmentation of the Golgi similar to that of dynamitin. These results suggest that CG-NAP is recruited to the minus ends of microtubules by interacting with cytoplasmic dynein, thereby localizes to the Golgi apparatus in a microtubule dependent manner and possibly involved in the formation of the Golgi near the centrosomes. PMID- 17352747 TI - Silver treatments for leg ulcers: a systematic review. AB - To determine the quantity and quality of current research on the effectiveness of silver-based dressings and topical agents for the treatment of leg ulcers, this paper presents a systematic review of randomized controlled trials (RCTs) looking at the effects of silver-based dressings and topical agents on leg ulcer healing. Electronic databases were searched up to May 2006 for relevant randomized controlled trials. Journals and conference proceedings were also searched. The methodological quality of selected trials was assessed and statistical pooling of the results from similar studies undertaken. Rate of healing, proportion of ulcers completely healed and change in ulcer size were observed. Nine studies were considered eligible for inclusion. These studies varied in terms of the types of leg ulcers treated, interventions used, and outcomes assessed. Studies provided inconsistent evidence regarding the effects of silver-based dressings and topical agents on leg ulcer healing. Studies generally provided poor evidence due to a lack of statistical power, poor study designs, and incomplete reporting. In conclusion, the current evidence base on the use of these silver-based products on leg ulcers is limited, both in terms of the quantity available and the quality of the evidence. This review highlights the need for further, more rigorous research to be carried out before the use of these silver-based interventions in routine leg ulcer management is supported. PMID- 17352748 TI - Effect of oral hydration on skin microcirculation in healthy young and midlife and older adults. AB - Clinically undetected underhydration lowers subcutaneous tissue oxygen, impairs healing and increases wound infection. This study examined the effect of supplemental oral hydration on noninvasive measures of skin temperature (T(s)), transcutaneous skin O(2) (PtcO(2)), and CO(2) (PtcCO(2)), and skin blood flow (laser Doppler fluxmetry [Flux]=concentration of moving blood cells [CMBC] x Velocity) in healthy adults. Nineteen Control and 18 Test (Hydrated) subjects participated. Ad libitum fluid intake was allowed before the experiment. Sensors were placed on the chest, lower legs, and feet. Time 1 resting supine T(s), PtcO(2)/PtcCO(2), and Flux/CMBC/Velocity were obtained. Then, the Test group ingested 500 mL of H(2)O. Time 2 measures were obtained 30 minutes later. Data were analyzed using ANOVA. Change in T(s), PtcO(2), PtcCO(2), and Velocity did not differ between groups. Flux increased more in the Test than in the Control group (p<0.01). The Flux change was explained by a CMBC increase (p<0.05). For midlife/older subjects only, the CMBC change was greater in the Test than in the Control group (p<0.01). Flux may be sufficiently sensitive to detect microvascular changes in response to supplemental oral hydration. These data also suggest that subtle levels of hypoperfusion due to underhydration may exist in community-dwelling healthy midlife/older adults in their natural state. PMID- 17352749 TI - Painful leg ulceration: a prospective, longitudinal cohort study. AB - This study aimed to explore the relationship between pain mechanism, pain intensity, and leg ulcer characteristics using a 6-month longitudinal cohort study in a community setting in the north of England. Patients with leg ulceration referred consecutively to district nurses were invited to participate (n=96). The main outcome measures were pain intensity using daily visual analogue scores, leg ulcer characteristics (etiology, size, location, duration), and LANSS (Leeds Assessment of Neuropathic Symptoms and Signs). Results suggested that type, duration, position, and size of the leg ulcer had no effect on average daily pain scores. Using the LANSS questionnaire, 43.5% of respondents reported symptoms suggestive of a neuropathic mechanism to their pain. Patients with neuropathic symptoms had higher average daily pain scores (p<0.001). Fewer people had healed ulcers at 6 months with neuropathic symptoms compared with those with no neuropathic symptoms (30.8 vs. 52.1%). It would seem that the severity of pain can not be predicted by the type, size, position, or duration of ulceration. Patients who scored positively for neuropathic symptoms had higher average daily pain scores and fewer had healed leg ulcers at 6 months compared with those who did not experience neuropathic signs and symptoms. PMID- 17352750 TI - Randomized clinical trial comparing two options for postoperative incisional care to prevent poststernotomy surgical site infections. AB - Surgical site infection (SSI) remains an important complication of cardiac surgery. Prevention is important, as SSI is associated with high mortality and morbidity rates. Incisional care is an important daily issue for surgeons. However, there is still scant scientific evidence on which guidelines can be based. A randomized clinical trial was performed to compare two options for postoperative incisional care. Patients undergoing sternotomy for cardiothoracic surgery were eligible. To protect an incision from exogenous contamination or direct inoculation by endogenous pathogens, the study group received an adhesive drape, impermeable to water and air. The control group was treated with a water- and air-permeable absorbent dressing. Primary outcome measure was SSI. Between March 2003 and January 2005, 1,185 patients were included. Both groups were comparable for base-line characteristics. No significant difference was found in the incidence of sternal SSI between groups (2.6 vs. 3.3%). In our study, an incisional-care program using a sterile, impermeable adhesive drape did not perform better than an absorbent dressing in reducing SSI after cardiothoracic surgery. In our view, future studies in the field of prevention of SSI should concentrate on other areas of interest. PMID- 17352751 TI - Randomized trial of two foam dressings in the management of chronic venous ulceration. AB - A multicenter prospective randomized clinical trial was undertaken to compare two foam dressings (Allevyn Hydrocellular, Smith & Nephew and Mepilex, Molnlycke Health Care AB) in the management of chronic venous leg ulceration. Patients were also randomized to two compression bandage systems (4-layer vs. cohesive short stretch) as a factorial design. Those with causes of ulceration other than venous disease were excluded. In all, 156 patients met the entry criteria and were randomized from the 12 clinical centers with a median (range) ulcer size of 4.33 (0.33-123.10) cm(2). After 24 weeks a total of 100 (64.1%) patients had complete ulcer closure, 46 (29.5%) had withdrawn from the trial, nine (5.8%) remained unhealed and one patient died. Of the patients randomized to Mepilex, 50/75 (66.7%) had complete ulcer healing compared with 50/81 (61.7%) on Allevyn. The hazard ratio for healing after adjustment for bandage type and trial center was 1.48 (95% C.I. 0.87-2.54, p=0.15), which only marginally changed following adjustment for baseline variables, neither of which achieved statistical significance (p=0.16). Withdrawal rates were similar between groups (23, 30.7% Mepilex vs. 23, 28.4% Allevyn). Pain improved following treatment with both dressings (p<0.001), but with no difference between dressings. PMID- 17352752 TI - Reduced up-regulation of cytoprotective genes in rat cutaneous tissue during the second cycle of ischemia-reperfusion. AB - Chronic wounds are major health problems that affect millions of people in the United States every year. Management of these wounds costs billions of dollars annually in the United States. Despite their clinical importance, the molecular mechanisms underlying these clinical conditions remain elusive. Repetitive ischemia-reperfusion (I-R) may play a pivotal role in chronic wound formation. The development of therapies for these wounds is hindered by the lack of animal models that allow identification of the molecular mechanisms underlying chronic wound formation. In the first study of its kind, we adapted our rat pressure sore model by imposing two cycles of ischemia (2 hours) and two cycles of reperfusion (24 hours), and we examined gene expression to better understand the molecular events that occur at the very early stages of cutaneous I-R injury with a goal of devising preventing strategies. We successfully tested our hypothesis and demonstrated that while cytoprotective genes, such as heat shock protein 70, heat shock protein 90, hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and heme oxygenase-1, were initially up-regulated during the first cycle of I-R, their up-regulation was subsequently reduced or completely abolished during the second cycle of I-R. These findings raise the possibility that reduced up-regulation of these cytoprotective genes may be causally linked to cutaneous I R injury. PMID- 17352753 TI - Trehalose lyophilized platelets for wound healing. AB - Fresh platelet preparations are utilized to treat a wide variety of wounds, although storage limitations and mixed results have hampered their clinical use. We hypothesized that concentrated lyophilized and reconstituted platelet preparations, preserved with trehalose, maintain and possibly enhance fresh platelets' ability to improve wound healing. We studied the ability of a single dose of trehalose lyophilized and reconstituted platelets to enhance wound healing when topically applied on full-thickness wounds in the genetically diabetic mouse. We compared these results with the application of multiple doses of fresh platelet preparations and trehalose lyophilized and reconstituted platelets as well as multiple doses of vascular endothelial growth factor (VEGF) and wounds left untreated. Trehalose lyophilized and reconstituted platelets, in single and multiple applications, multiple applications of fresh platelets and multiple applications of VEGF increased granulation tissue deposition, vascularity, and proliferation when compared with untreated wounds, as assessed by histology and immunohistochemistry. Wounds treated with multiple doses of VEGF and a single dose of freeze-dried platelets reached 90% closure faster than wounds left untreated. A single administration of trehalose lyophilized and reconstituted platelet preparations enhanced diabetic wound healing, therefore representing a promising strategy for the treatment of nonhealing wounds. PMID- 17352754 TI - Shift of homeostasis from parenchymal regeneration to fibroblast proliferation induced by lipopolysaccharide-activated macrophages in gastric mucosal healing in vitro. AB - Wound healing in the gastrointestinal tract is an orderly process involving orchestrated responses of various cell types. Lipopolysaccharides (LPS) are major components of the outer membrane of Gram-negative bacteria, which are known to impair gastric ulcer healing in animals. The influence of LPS on intercellular communication in wound healing, however, is unknown. We examined the effects of LPS-induced macrophage activation on the proliferative response in cultured rat gastric epithelial cells (RGM-1) and fibroblasts JHU-25. Rat peritoneal resident macrophages were activated with increasing doses of LPS. The supernatant from the activated macrophage preparation, designated as macrophage-conditioned medium, was then used to treat RGM-1 or JHU-25 cells. Cell proliferation and migration were determined by [(3)H]-thymidine incorporation and a monolayer wound-healing assay, respectively. Macrophage-conditioned medium significantly suppressed RGM-1 cell proliferation but had no effect on cell migration. The same medium, however, increased JHU-25 cell proliferation. LPS treatment alone suppressed JHU-25 cell proliferation while it had no effect on RGM-1 cell proliferation, indicating that the differential effects of the macrophage-conditioned medium on cell proliferation were elicited by the factors derived from macrophages. In this regard, tumor necrosis factor (TNF)-alpha stimulated while interleukin (IL)-1beta suppressed RGM-1 cell proliferation, suggesting that IL-1beta but not TNF-alpha may play a part in the mediation of the antiproliferative effect of macrophage conditioned medium on gastric epithelial cells. In contrast, IL-1beta suppressed while TNF-alpha had no effect on JHU-25 cell proliferation. Collectively, LPS activated macrophages delay gastric mucosal regeneration but promote fibroblast proliferation in vitro. Such changes may partly elucidate the detrimental effect of bacterial infection on tissue repair in the stomach. PMID- 17352755 TI - A silicone-based controlled-release device for accelerated proteolytic debridement of wounds. AB - A new device for rapid enzymatic debridement of cutaneous wounds has been developed using a controlled-release, silicone-based, dried emulsion. A dehydrated serine protease of the subtilisin family, previously untested for wound debridement, was incorporated into the emulsion. This device exhibited excellent storage stability. Moisture from the wound triggered an even, reproducible, and complete release of the enzyme within the first 8 hours. The device maintains a moist wound environment that allows the enzyme to achieve nearly complete digestion of the hardened eschar of full-thickness burns in a porcine model after an exposure period of 24 hours. Debridement was faster than in untreated wounds or wounds treated with a currently available enzyme ointment. Following rapid enzymatic debridement, healing appeared to progress normally, with no histological evidence of damage to adjacent healthy tissue. PMID- 17352756 TI - Keratinocyte conditioned medium abrogates the modulatory effects of IGF-1 and TGF beta1 on collagenase expression in dermal fibroblasts. AB - Overexpression of wound healing-promoting factors such as transforming growth factor-1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1) during the healing process has been implicated in the development of dermal fibrosis in patients following thermal injury, surgical incision, and deep trauma. However, the mechanism through which the expression of these two fibrogenic factors is slowed down and/or abrogated in the late stages of the healing process is not known. Here, we hypothesize that keratinocyte-releasable factors counteract the fibrogenic role of both IGF-1 and TGF-beta1 in fibroblasts. To test this hypothesis, the levels of collagenase (MMP-1), as an index for extracellular matrix degradation, in dermal fibroblasts in response to either keratinocyte conditioned medium (KCM) or our recently identified keratinocyte-releasable stratifin in the presence and absence of either IGF-1, TGF-beta1, or both were evaluated. The results of Northern analysis showed a significant increase in collagenase mRNA expression in cells treated with KCM in the presence of both IGF 1 and TGF-beta1. The effect was, at least in part, due to keratinocyte-derived stratifin that was present in KCM. This was ascertained as the levels of MMP-1 mRNA were markedly reduced when cells were treated with stratifin-immuno-depleted KCM. The results of Western blot analysis showed an increase in the level of MMP 1 protein in stratifin-treated fibroblasts and this was consistent with the level of MMP-1 mRNA expression detected by Northern analysis. However, in contrast to KCM, whose efficacy on MMP-1 expression was modestly reduced by either IGF-1 and TGF-beta1, or a combination of both, these factors abrogated the MMP-1 stimulatory effect of stratifin in fibroblasts. In summary, the results of this study revealed that both stratifin and KCM stimulate the expression of MMP-1-in fibroblasts and this effect can be abrogated by either IGF-1, TGF-beta1, or a combination of both. PMID- 17352757 TI - Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing. AB - We describe synthetic extracellular matrix (sECM) hydrogel films composed of co crosslinked thiolated derivatives of chondroitin 6-sulfate (CS) and heparin (HP) for controlled-release delivery of basic fibroblast growth factor (bFGF) to full thickness wounds in genetically diabetic (db/db) mice. In this model for chronic wound repair, full-thickness wounds were treated with CS, CS-bFGF, or CS-HP-bFGF films. At 2 and 4 weeks postinjury, wound closure and formation of the new epidermis and dermis were determined. Both CS and CS-HP hydrogel films accelerated wound repair, even without bFGF. Addition of bFGF to CS films showed partial dose-dependent acceleration of wound repair. Importantly, addition of bFGF to co-crosslinked CS-HP sECM films showed a dramatic bFGF dose-dependent acceleration of wound healing, as well as improved dermis formation and vascularization. Compared with 27% wound closure in 2 weeks in the controls, 89% wound closure was observed for mice treated with the CS-HP-bFGF films. The synthetic CS-HP sECM films mimic the chemistry and biology of heparan sulfate proteoglycans, and may have clinical potential for topical delivery of growth factors to patients with compromised wound healing. PMID- 17352758 TI - Tissue concentration of transforming growth factor beta1 and basic fibroblast growth factor in skin wounds created with a CO2 laser and scalpel: a comparative experimental study, using an animal model of skin resurfacing. AB - Although a number of ablative-laser techniques based on CO(2) and Er: YAG laser devices have been successfully developed and used in the clinical setting, the bio-molecular processes influencing wound healing after exposure to laser energy are not well elucidated. In this study, we aim to assess the impact of the mechanism of injury on the secretion of transforming growth factor beta1 (TGF beta1) and basic fibroblast growth factor (bFGF) in various stages of wound healing, in wounds created with a CO(2) laser and scalpel. Ten Wistar rats were used to determine the levels of growth factor proteins TGF-beta1 and bFGF after CO(2) laser- and scalpel-induced skin injury. Tissue was excised on day 0 for untreated skin (control sites), and on days 1, 10, 30, and 90 following laser and scalpel surgery. Specimens were processed for histopathological analysis and for determining the concentration of growth factors by a Western blot technique. The concentration of TGF-beta1 increased markedly, at day 1 postinjury, from a baseline of 130+/-16 mm(2) (mean surface area of blotted-protein lanes) to 261+/ 23 mm(2) and 394+/-22 mm(2) for laser-inflicted injury and scalpel wounds, respectively; the latter values were found to differ significantly (p<0.001). The concentration of b-FGF on day 10 postinjury differed significantly (p<0.001) between the laser sites (553+/-45 mm(2)) and the corresponding scalpel sites (418+/-41 mm(2)). Laser energy alters local tissue secretion of TGF-beta1 and bFGF of skin injuries created with the CO(2) laser compared with wounds created with a scalpel. These differences might have an impact on various aspects of wound healing of skin injuries created by a laser. PMID- 17352759 TI - Local injection of insulin-zinc stimulates DNA synthesis in skin donor site wound. AB - Our group has reported the ability of local insulin-zinc injection to accelerate skin wound healing. This experiment was conducted to investigate the metabolic mechanisms of locally injected insulin-zinc in accelerating wound healing. A partial thickness skin donor site wound was created on the back, and indwelling catheters were placed in the carotid artery and jugular vein in anesthetized rabbits. On day 7 after injury, the wound was either injected with 0.2 U of insulin-zinc, 0.4 microg zinc (the amount of zinc in 0.2 U of insulin-zinc), or not injected; stable isotope tracers were infused for measurement of wound DNA synthetic rate as a reflection of cell proliferation. Wound protein synthetic and breakdown rates were also measured. The local insulin-zinc injection increased wound insulin concentration from below 5 pmol/L to 1,260+/-780 pmol/L with minor changes in blood glucose concentration that did not require exogenous glucose replacement. In the insulin-zinc-injected wound, the total DNA synthetic rate was increased by approximately 50% (p<0.05 vs. control). In the zinc-injected wound, whereas total DNA synthetic rate was increased (p<0.05 vs. control), net protein deposition (synthesis-breakdown) was less (p<0.05) than those in the control and insulin-zinc groups. We conclude that local insulin-zinc injection stimulates wound DNA synthesis, which would be expected to accelerate wound reepithelialization. PMID- 17352760 TI - Hyperbaric oxygen stimulates epidermal reconstruction in human skin equivalents. AB - The crucial role of oxygen during the complex process of wound healing has been extensively described. In chronic or nonhealing wounds, much evidence has been reported indicating that a lack of oxygen is a major contributing factor. Although still controversial, the therapeutic application of hyperbaric oxygen (HBO) therapy can aid the healing of chronic wounds. However, how HBO affects reepithelization, involving processes such as keratinocyte proliferation and differentiation, remains unclear. We therefore used a three-dimensional human skin-equivalent (HSE) model to investigate the effects of daily 90-minute HBO treatments on the reconstruction of an epidermis. Epidermal markers of proliferation, differentiation, and basement membrane components associated with a developing epidermis, including p63, collagen type IV, and cytokeratins 6, 10, and 14, were evaluated. Morphometric analysis of hematoxylin and eosin-stained cross sections revealed that HBO treatments significantly accelerated cornification of the stratum corneum compared with controls. Protein expression as determined by immunohistochemical analysis confirmed the accelerated epidermal maturation. In addition, early keratinocyte migration was enhanced by HBO. Thus, HBO treatments stimulate epidermal reconstruction in an HSE. These results further support the importance of oxygen during the process of wound healing and the potential role of HBO therapy in cutaneous wound healing. PMID- 17352761 TI - Digit tip regrowth and differential gene expression in MRL/Mpj, DBA/2, and C57BL/6 mice. AB - MRL/Mpj mice are the only known strain of mouse that can regenerate cardiac lesions and completely heal ear punches without scarring. This study was undertaken to determine if MRL mice also have greater regrowth capabilities in amputated digit tips. Right paw digit tips of neonatal MRL mice were dissected, with the left front paws as uncut controls. Controls used for regrowth comparison were the DBA/2 and C57BL/6 inbred mouse strains. Consecutive x-ray images were captured of front paws at 0, 7, 14, 21, and 28 days postamputation. MRL mouse digit tips were found to distally regrow more quickly and reform nails partially and completely to a greater degree in comparison with DBA and B6 mice (p<0.05). We next undertook microarray expression analysis to identify the genes involved in digit tip regrowth. Four hundred genes out of 15,000 were significantly differentially expressed (p<0.05) in MRL, DBA, and B6 mice at day 4 in comparison with day 0 control tissue. Multiple differences between MRL, DBA, and B6 strains were found in genes that are implicated in the WNT signaling pathway and transcription. We conclude that MRL mice regrow digits distally more rapidly and partially and completely regrow nails to a greater degree than B6 and DBA strains. This enhanced regrowth is likely due to strain-specific increased expression of genes involved in growth and development. PMID- 17352762 TI - Long-term survival of HIV-infected patients treated with highly active antiretroviral therapy in Serbia and Montenegro. AB - BACKGROUND: Highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of HIV disease, even in terminally ill patients. Although these patients may survive many years after the diagnosis of AIDS if treated with HAART, some still die during treatment. METHODS: A retrospective study in a cohort of 481 HIV-infected patients treated with HAART between January 1998 and December 2005 was conducted to compare subgroups of long-term survivors (LTSs) and patients who died during treatment. RESULTS: A total of 48 patients survived for more than 72 months (mean 83.8+/-standard deviation 5.6 months). Thirty patients died during treatment (mean 35.3+/-25.0 months), of whom nine died from non-AIDS-related causes, 18 died from AIDS-related causes, and three died as a result of HAART toxicity. Although LTSs were significantly (P=0.015) younger at HAART initiation, age below 40 years was not a predictor of long-term survival. The subgroups did not differ in the proportion of clinical AIDS cases at HAART initiation, in the prevalence of hepatitic C virus (HCV) coinfection, or in pretreatment and end-of-follow-up CD4 cell counts. In contrast, the viral load achieved during treatment was lower in the survivors (P=0.03), as was the prevalence of hepatitis B virus (HBV) coinfection (P=0.03). Usage of either protease inhibitor (PI)-containing regimens [odds ratio (OR) 9.0, 95% confidence interval (CI) 2.2-35.98, P<0.001] or all three drug classes simultaneously (OR 7.4, 95% CI 2.2-25.1, P<0.001) was associated with long-term survival. Drug holidays incorporated in structured treatment interruption (STI) were also associated with a good prognosis (OR 14.9, 95% CI 2.9-75.6, P<0.001). CONCLUSIONS: Long-term survival was associated with PI-based HAART regimens and lower viraemia, but not with the immunological status either at baseline or at the end of follow up. STI when CD4 counts reach 350 cells/microL, along with undetectable viraemia, was a strong predictor of long-term survival. PMID- 17352763 TI - Superior virological response to boosted protease inhibitor-based highly active antiretroviral therapy in an observational treatment programme. AB - BACKGROUND: The use of boosted protease inhibitor (PI)-based antiretroviral therapy has become increasingly recommended in international HIV treatment consensus guidelines based on the results of randomized clinical trials. However, the impact of this new treatment strategy has not yet been evaluated in community treated cohorts. METHODS: We evaluated baseline characteristics and plasma HIV RNA responses to unboosted and boosted PI-based highly active antiretroviral therapy (HAART) among antiretroviral-naive HIV-infected patients in British Columbia, Canada who initiated HAART between August 1997 and September 2003 and who were followed until September 2004. We evaluated time to HIV-1 RNA suppression (<500 HIV-1 RNA copies/mL) and HIV-1 RNA rebound (>or=500 copies/mL), while stratifying patients into those that received boosted and unboosted PI based HAART as the initial regimen, using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: During the study period, 682 patients initiated therapy with unboosted PI and 320 individuals initiated HAART with a boosted PI. Those who initiated therapy with a boosted PI were more likely to have a CD4 cell count <200 cells/muL and to have a plasma HIV RNA>100 000 copies/mL, and to have AIDS at baseline (all P<0.001). However, when we examined virological response rates, those who initiated HAART with a boosted PI achieved more rapid virological suppression [relative hazard 1.26, 95% confidence interval (CI) 1.06-1.51, P=0.010]. CONCLUSIONS: Patients prescribed boosted PIs achieved superior virological response rates despite baseline factors that have been associated with inferior virological responses to HAART. Despite the inherent limitations of observational studies which require this study be interpreted with caution, these findings support the use of boosted PIs for initial HAART therapy. PMID- 17352764 TI - Cytochrome P450 2B6 (CYP2B6) G516T influences nevirapine plasma concentrations in HIV-infected patients in Uganda. AB - OBJECTIVES: Polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been shown to influence nevirapine plasma concentrations in HIV-infected European Caucasians. Although nevirapine is used extensively in Africa, the influence of CYP2B6 genotype on nevirapine exposure has not been assessed in this population. We aimed to determine the influence of CYP2B6 genotype at position 516 on nevirapine trough concentrations in HIV-infected patients in Kampala, Uganda. Additional polymorphisms in the CYP and multidrug resistance protein-1 (MDR-1) genes were also assessed for their impact on nevirapine concentrations. METHODS: The following genotypes were determined in all subjects using polymerase chain reaction-restriction fragment length polymorphism: CYP2B6 G516T, MDR-1 C3435T and G2677T, CYP3A4(*)1B and CYP3A5(*)3. Nevirapine plasma concentrations were determined using high-performance liquid chromatography in 23 HIV-infected patients who were generally healthy and had been taking nevirapine 200 mg twice daily for at least 14 days. Analysis of variance with post hoc testing was used to compare nevirapine concentrations among CYP2B6 genotype groups. RESULTS: The median nevirapine trough concentration in individuals homozygous for the variant allele (TT) was 7607 ng/mL vs 4181 and 5559 ng/mL for GG and GT individuals, respectively (GG vs TT median ratio=1.82; P=0.011). The mean ratio for TT vs GG individuals (95% confidence interval) was 1.51 (1.18, 1.84). No associations were observed between the other polymorphisms studied and nevirapine concentrations. CONCLUSIONS: CYP2B6 G516T significantly influenced nevirapine trough concentrations in HIV-infected patients in Uganda. Additional studies in larger patient populations are necessary to further define the potential clinical impact of these preliminary findings. PMID- 17352765 TI - Quality of life and depression among HIV-infected patients receiving efavirenz- or protease inhibitor-based therapy in Senegal. AB - BACKGROUND: Efavirenz has been associated with neuropsychiatric disorders, but little is known about depression and quality of life in sub-Saharan Africa, where nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are still the first-line treatment recommended by the World Heath Organization (WHO) and are widely prescribed. METHODS: In a cross-sectional study, we evaluated quality of life and depression among Senegalese patients receiving efavirenz- or protease inhibitor (PI)-based regimens. Two hundred consecutive patients who had been taking highly active antiretroviral therapy (HAART) for more than 6 months were asked to complete a questionnaire. RESULTS: According to the Center for Epidemiologic Studies Depression Scale (CES-D), 18% had depression (19% for patients on a PI-based regimen and 17% for patients on efavirenz-based treatment). Fifty-nine per cent of the patients reported no health problems in the past 4 weeks. A quarter of patients had sleep disorders. Moderate or slight adverse events were reported by 28.5% of patients. CONCLUSIONS: Quality of life and depression scores remained good in both study groups. However, quality of life and depression should be monitored in follow-up of HIV-infected patients in sub-Saharan Africa. PMID- 17352766 TI - Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death. AB - OBJECTIVES: The aim of the study was to compare incidence rates (IRs) of AIDS/death in patients with and without treatment interruption (TI) of combination antiretroviral therapy (cART) for periods of 3 months or more for different categories of CD4 cell count and viral load, and to determine risk factors for clinical progression to AIDS/death. METHODS: Patients starting cART with a CD4 cell count and a viral load available within 6 months of starting cART were included in the study. The IR and risk factors of TI were determined. We assessed the incidence rate ratios (IRRs) for TI and AIDS/death events using Poisson regression models. RESULTS: Of 3811 patients included in the study, 26% were ART-naive prior to cART. The median date of starting cART was July 1997, the median CD4 cell count was 226 cells/microL and the median viral load was 4.36 log(10) HIV-1 RNA copies/mL. We observed 1243 interruptions and 403 AIDS events/deaths. The IR of AIDS/death was higher in patients with lower CD4 cell counts or higher viral loads, regardless of TI. After adjusting for baseline factors, the IR of AIDS/death was significantly higher in the TI group than in the non-TI group [IRR 2.63; 95% confidence interval (CI) 2.01-3.44; P<0.0001]; this could be explained by current CD4 cell counts and viral loads, as the CD4 cell count- and viral load-adjusted IRR was 1.14 (95% CI 0.86-1.51; P=0.37). Within the TI group, patients with a current CD4 cell count of <200 cells/microL had a 3-fold higher risk of AIDS/death than those with a CD4 cell count of 200 350 cells/microL, whereas patients with a current CD4 cell count of >350 cells/microL had a 4-fold lower risk of disease progression. CONCLUSIONS: TI is common in clinical practice. The risk of AIDS/death increased more than 2-fold for patients stopping all cART regimen drugs for 3 months or more. Among patients experiencing a TI, those with low CD4 cell counts, high viral loads or prior AIDS had an increased risk of AIDS/death. Hence, TI should be discouraged and closely monitored if it occurs. PMID- 17352767 TI - Limitation of exercise capacity in nucleoside-treated HIV-infected patients with hyperlactataemia. AB - BACKGROUND: Inhibition of DNA polymerase gamma by nucleoside reverse transcriptase inhibitors (NRTIs) can cause mitochondrial dysfunction and cellular toxicity. Hyperlactataemia, which is a consequence of a shift in the metabolism of pyruvate, is an indicator of nucleoside-related mitochondrial toxicity. METHODS: We evaluated exercise and oxidative capacities as well as circulatory and ventilatory responses to exercise in 24 HIV-infected patients on NRTIs presenting hyperlactataemia [mean (+/-standard deviation) fasted lactate=3.5+/ 1.1 mmol/L]; 27 NRTI-treated patients with normal baseline lactate concentrations were used as controls (mean fasted lactate=1.6+/-0.3 mmol/L). RESULTS: In the patients with hyperlactataemia, the average peak work capacity (1.7+/-0.6 W/kg) and peak oxygen consumption (VO(2)) (21+/-4 mL/kg/min) were significantly lower (P<0.01) than in control subjects (work, 2.1+/-0.4 W/kg; VO(2), 25+/-4 mL/kg/min). The capacity to increase oxygen extraction during exercise was significantly diminished in the hyperlactataemia group, as shown by a low peak systemic arteriovenous oxygen difference (a-vO(2)) difference compared with controls (11+/-3 vs 14+/-3 mL/dL; P=0.008), and as indicated by a linear correlation between VO(2) and systemic a-vO(2) difference (r(2)=0.76). During exercise, the increases in cardiac output relative to VO(2) (mean Delta cardiac output (Q)/DeltaVO(2)=8+/-3.6) and ventilation (mean Delta ventilation (VE)/DeltaVO(2)=48.6+/-13.2) were significantly higher in hyperlactataemia patients compared with controls (mean cardiac output Delta(Q)/DeltaVO(2)=6+/-2; mean DeltaVE/DeltaVO(2)=42+/-12.7; P=0.03). CONCLUSIONS: The degree of exercise limitation in patients with nucleoside-related mitochondrial toxicity correlates directly with the severity of impaired muscle oxidative phosphorylation, as indicated by the capacity for muscle oxygen extraction. Exaggerated circulatory and ventilatory responses to exercise are direct consequences of the level of impaired muscle oxidative phosphorylation. PMID- 17352768 TI - Predictors of CD4 count change over 8 months of follow up in HIV-1-infected patients with a CD4 count>or=300 cells/microL who were assigned to 7.5 MIU interleukin-2. AB - BACKGROUND: ESPRIT is a randomized trial comparing the clinical impact of interleukin (IL)-2 plus antiretrovirals vs antiretrovirals alone. Identification of factors that influence the relationship between IL-2 and CD4 count recovery will enable better personalization of treatment with IL-2 in HIV-1-positive individuals. The IL-2 induction phase consists of three dosing cycles over 6-8 months (7.5 MIU twice a day, for 5 days every 8 weeks). METHODS: We included patients initiating IL-2 at the 7.5 MIU dose with an 8-month CD4 count, measured at least 30 days after their last cycle. We identified baseline predictors of CD4 count changes over 8 months using linear regression. RESULTS: Of 2090 patients assigned IL-2, 1673 (80%) were included in the analysis. The median (interquartile range) baseline CD4 count was 461 (370, 587) cells/microL with a median increase of 233 (90, 411) cells/microL at month 8. After adjustments, significant predictors of CD4 count change included CD4 nadir (29.8 cells/microL greater increase per 100 cells/microL higher; P<0.0001), last CD4 count before baseline (mean 36.0 cells/microL greater increase per 100 cells/microL higher; P<0.0001), time from antiretroviral start to baseline (8.3 cells/microL smaller increase per year longer; P=0.001), age (11.7 cells/microL smaller increase per 5 years older; P=0.005) and race (79.7 cells/microL greater increase for black patients vs white patients; P=0.003). A linear relationship existed between total IL-2 dose in the first cycle and CD4 count change (73.1 cells/microL greater increase per 15 MIU higher; P<0.0001). CONCLUSIONS: Prior nadir and current CD4 counts, age and IL-2 dose are major determinants of CD4 increases induced by with intermittent administration of IL-2 in HIV-1-positive individuals on antiretrovirals. The clinical function of these induced CD4 cells is under study. PMID- 17352769 TI - HIV-associated Isospora belli infection: incidence and risk factors in the French Hospital Database on HIV. AB - OBJECTIVE: To determine the incidence of Isospora belli infection in HIV-infected patients in France, and to study risk factors. METHODS: The French Hospital Database on HIV (FHDH) is a prospective cohort study that collects demographic, clinical and therapeutic data on patients managed in 62 hospitals. We reviewed all cases of I. belli infection recorded between 1992 and 2003. We compared the incidence in 1992-1994 [before the use of dual therapy and combination antiretroviral therapy (cART)] and in 1997-2003 (when use of cART was widespread), after stratification for CD4 cell count (< 50, 50-99, 100-199 and > 200 cells/microL). RESULTS: A total of 164 patients had I. belli infection either at enrollment (n=71) or during follow up (n=93). During the study period, I. belli infection tended to occur less frequently during follow up, and to be diagnosed mainly at database enrollment. The incidence of I. belli infection during follow up fell by 79% [relative hazard (RH) 0.21; 95% confidence interval (CI) 0.13-0.33] in the cART period compared with the pre-cART period; no such change was noted among patients with CD4 cell counts below 50 cells/microL. In multivariable analysis, the risk of I. belli infection was significantly higher among patients from sub-Saharan Africa (RH 4.3; 95% CI 2.6-7.3). After adjustment for CD4 cell count, patients receiving cotrimoxazole prophylaxis were found to be at a lower risk of I. belli infection (RH 0.3; 95% CI 0.2-0.6). CONCLUSIONS: In France, I. belli infection among HIV-infected patients is now mainly seen in patients from sub-Saharan Africa, who present at an advanced stage. PMID- 17352771 TI - Discourse, responsible research and positioning the subject. PMID- 17352770 TI - Pharmacokinetic interaction between rifampicin and ritonavir-boosted atazanavir in HIV-infected patients. AB - BACKGROUND: Tuberculosis (TB) is a common opportunistic infection among HIV infected people, and rifampicin is an important drug for the treatment of TB. However, administration of rifampicin in combination with antiretroviral therapy, particularly protease inhibitors, is difficult because of drug-drug interactions. METHODS: We have performed a prospective study in three HIV-infected patients with TB treated with a rifampicin-containing regimen (rifampicin 600 mg per day) and antiretroviral therapy including only nucleoside reverse transcriptase inhibitors (NRTIs) plus atazanavir 300 mg once a day (qd) and ritonavir 100 mg qd, to evaluate whether the inducing effect of rifampicin on the drug metabolizing enzyme cytochrome P450 (CYP) 3A4 could be overcome by the inhibitory effect of ritonavir. A complete pharmacokinetic evaluation of the steady-state concentrations of atazanavir and ritonavir was performed. RESULTS: In all three cases, more than 50% of the time the atazanavir level was below the minimum recommended trough plasma level (150 ng/mL according to current pharmacokinetic guidelines) to inhibit HIV wild-type replication. CONCLUSION: These results strongly indicate that the administration of rifampicin with a combination of atazanavir 300 mg qd plus ritonavir 100 mg qd must be avoided because subtherapeutic concentrations of atazanavir are produced. PMID- 17352772 TI - Mental health practitioner's attitude towards maintenance neuroleptic treatment for people with schizophrenia. AB - Pharmacological relapse prevention treatment for people with schizophrenia can last for years if not the person's lifetime. The attitude mental health practitioners (MHPs) hold regarding this treatment can have profound effects on service users' decisions related to treatment. The small number of studies focusing on this issue concentrates on the use of 'depot' preparations. To develop a validated inventory to assess the attitudes of MHPs towards treatment and evaluate the attitudes of a sample of MHPs. The inventory was developed in three stages; item selection, piloting and psychometric testing. The validated inventory was administered to a sample of 50 MHPs undertaking a degree level course in the psycho-social management of psychosis. The final inventory consisted of 21 attitudinal items and four items related to the practitioner's confidence. Results from the sample revealed areas of agreement, variation and uncertainty. A valid and reliable inventory has been developed. The administration of the inventory to 50 MHPs returned results which reflect variable attitudes and perceptions of competency towards maintenance neuroleptic treatment. This diversity in attitudes may have an impact on management of people with a diagnosis of schizophrenia and clinical outcomes. PMID- 17352773 TI - Aggression and violence in mental health services: categorizing the experiences of Irish nurses. AB - There is growing evidence that nurses in mental health services are likely to be victims of violence or aggression. One of the key difficulties in comparing international findings, however, has been that there has been an inadequate categorization of the types of incident to which staff are exposed. The current study aimed to identify the types of violent or aggressive incidents that staff in Irish Mental Health Services were exposed to within a 1-month long period. A cross-sectional study was undertaken with all nurses working in one of the Mental Health Services in Ireland, serving both an urban and rural population. Data were collected through a questionnaire (Scale of Aggressive and Violent Experiences) adapted from the Perceptions of Prevalence of Aggression Scale. The questionnaire was designed to collect data relating to both personal and professional demographics of the sample as well as experiences of aggressive or violent incidents respondents may have encountered in their work situation. There was a response rate of 31%. Data were analysed utilizing SPSS-11. Both descriptive and inferential analyses were undertaken. The relevant data were subjected to a series of one-way ANOVAS and chi-squared analysis. The findings suggest that nursing staff in this Mental Health Service experienced high levels of verbal aggression, with distinctions obvious between threatening and non-threatening aggression, suggesting discernment in terms of intentionality. Additionally, respondents encountered greater levels of covert or indirect violence or aggression than forms that were overtly directed towards staff. The implications are discussed in relation to both policy and practice. PMID- 17352774 TI - Mental health and debt: challenges for knowledge, practice and identity. AB - People with mental health problems (MHPs) in Britain are nearly three times more likely to report debt compared with individuals without similar conditions. With one-in-four respondents with MHPs reporting personal debt, this may be equivalent to eight or nine clients in the recommended national community mental health nurses' (CMHNs) caseload of 35. Although client debt is not a new problem for CMHNs, it can pose significant difficulties for client well-being and nursing practice. This paper reviews the published literature on debt and mental health, then considers three of the challenges that client debt can present to: (1) nursing knowledge--moving away from understandings of client debt based on crisis, and towards those focused on process and prevention; (2) nursing practice -reworking the collaborative relationship between CMHNs and external debt advice agencies; and (3) nursing identity--managing the role conflicts that engaging with client debt can bring. The paper concludes by contending that nurses should raise and monitor debt issues among clients, but cannot be expected to become proxy 'debt advisors', with CMHNs being encouraged to increasingly collaborate with debt advisors (rather than simply referring on clients). PMID- 17352775 TI - Hope and interpersonal psychiatric/mental health nursing: a systematic review of the literature--part one. AB - Psychiatric/mental health (P/MH) nursing is inherently an interpersonal endeavour; one that includes a broad range of 'helping activities'. The interpersonal activities and skills are enshrined in our underpinning philosophy, explored and learned in our curricula (all around the world) and enacted in our everyday clinical practice. Within this interpersonal context and framework, it is heartening to see that understated, abstract and yet-lasting concepts such as hope are gaining more acknowledgement, recognition and subsequently attention. While it is recognized that hope in mental health care is increasingly becoming the focal point of disciplined inquiry, the authors believe it is perhaps necessary and timely to re-examine these two concepts, namely: interpersonal P/MH nursing and hope/inspiring hope in people with mental health problems. Accordingly, this two-part article reports on a systematic review of the literature that focuses on hope (inspiring hope) within interpersonal (counselling) focused P/MH nursing. Part one focuses on the method used and the results, indicating that a total of 57 articles were included in the review: 39 were categorized as empirical studies involving either a quantitative or qualitative methodological design, and 18 were considered theoretical/clinical/review articles. Though not a product of an empirical investigation per se, it was clear that many of the articles shared and covered common ground. Thus, these were arranged into six 'loose' thematic groupings. The first three of these areas, schizophrenia, suicidality and depression form the remainder of part one of this article, and the remaining areas are included in part two. PMID- 17352776 TI - Hope and interpersonal psychiatric/mental health nursing: a systematic review of the literature--part two. AB - This is the second of a two-part article which reports on a systematic review of the literature that focuses on hope (inspiring hope) within interpersonal (counselling) focused psychiatric/mental health (P/MH) nursing. Part one focused on the first three substantive areas, whereas this article focuses on the remaining areas and the discussion points arising out of the review. The discussion points arising are: (1) despite the increasing attention to hope over the last three decades, there remains a distinct paucity of research pertaining to P/MH nurses and hope, hoping and hopelessness; (2) the research that has been undertaken thus far lacks a cumulative, sequential progressive focus and has more of a sporadic, disparate look to it; (3) there is a dearth of empirical work to underpin specific interventions; (4) this relative absence of empirical work means that P/MH nurses often have to look to allied and/or related disciplines for their hope-related research; (5) there appears to be a disparity between the alleged importance of hope and the subsequent research activity; and (6) the research that does exist across different substantive areas appears to indicate that there might be common or shared basic psychosocial processes of hope inspiration, and thus the probability of a formal grounded theory; and this allows for idiosyncratic psychosocial processes for each substantive area. As a result of this review, the authors tentatively suggest that the inspiration of hope in P/MH nursing is grounded in the relationship established between nurse and person in need of hope, an emerging empirical finding that has obvious congruence and synchronicity with the philosophy and theory of a Peplauvian-based approach to P/MH nursing. PMID- 17352777 TI - Perspectives on the prevalence and treatment of personality disorder. AB - Personality disorder (PD) is the most prevalent psychiatric disorder. A methodical literature search identified that PD is under researched compared with other mental health problems such as depression or schizophrenia. Social and psychotherapeutic approaches emerge as dominant treatment approaches with PD where there is good evidence of efficacy. Collaborative group-based therapeutic approaches appear to offer a therapeutic counterpoise to the anti-social traits often prevalent in PD. A retrospective analysis of formal group therapy on acute inpatient units (treating PD patients among other mental health disorders) reveals only one violent incident in over 40,000 treatment hours of formal group therapy. It is argued that group-based and social therapy should be the recommended treatment approach because these approaches have been shown to create a safe and contained milieu, establishing a good base for therapeutic gain with PD patients. The case for widening the scope of collaborative group and community based therapies is considered and the merits and shortcomings of a key worker system with PD patients are critiqued. PMID- 17352778 TI - Bordering on insanity: misnomer, reviewing the case of condemned women. AB - In the UK, there have been calls to develop gendered specific mental health services for women in an attempt to ensure privacy and dignity are achieved as and when women come into contact with services. This is a largely rhetorical policy objective. There are more fundamental factors affecting women's experience of mental health services that need addressing. This paper explores these issues in the context of mental health care for women who have been 'given' the diagnosis of borderline personality disorder (BPD). Borderline personality disorder effects 2% of the adult population, 75-90% of those diagnosed being women. This diagnosis continues to present considerable conceptual and therapeutic challenges for all of those involved in mental health services and it remains a categorical label that evokes a wide range of conscious and unconscious responses in mental health nurses. The paper argues that mental health nurses need to recognize the defence mechanisms involved in working with individuals who are often difficult to work with. It is only when mental health nurses can embrace and acknowledge the person in the context of their life, that the pejorative and disabling consequences of the BPD label can be eliminated, ensuring the individual's story is heard and not that which is often a pre constituted account accompanying this diagnosis. PMID- 17352779 TI - Exploring the relationship between perceived emotional intelligence, coping, social support and mental health in nursing students. AB - Studies conducted with nurses or nursing students have shown that emotional intelligence is a skill that minimizes the negative stress consequences. The present work examines the role of perceived emotional intelligence (PEI) measured by the Trait Meta-Mood Scale, in the use of stress-coping strategies, in the quantity and quality of social support and in the mental health of nursing students. The results indicated positive correlations between clarity and social support, social support and repair, and social support and mental health. Hierarchy regression analysis pointed out that clarity and emotional repair are predictors of social support, and emotional repair is the main predictor of mental health. These results show the importance of PEI in stress coping within the nursing framework. PMID- 17352780 TI - Self-harm and the words that bind: a critique of common perspectives. AB - The issue of self-harm is not only a widespread phenomenon but also a challenging one. Nurses in particular are faced with this challenge, as they tend to be the primary professional group when working with people who self-harm within health service provision. The purpose of this paper is to offer a critical appraisal of common perspectives as reported in the existing literature. Having highlighted these areas, the paper will attempt to address the challenges faced by nurses and other healthcare professionals through the proposal of strategies, including the suggestion that self-harm may be considered from a position of social constructionism to achieve a more informed and effective response when working with someone who self-harms. PMID- 17352781 TI - A national survey of community psychiatric nurses and their client care activities in Ireland. AB - Increasingly, people with mental health problems in Ireland and in the UK are receiving mental health services in the community. The aim of this study was to identify the predominant approaches to care used by community psychiatric nurses (CPNs) and the theoretical bases of their practice. One hundred and sixteen questionnaires out of 203 sent to CPNs throughout Ireland were returned, giving a response rate of 57.1%. In addition, 33 home visits by 13 CPNs were observed. The findings showed that over 96% of the sample were in full-time employment; most (71.4%) worked a 9-5 weekday shift; 31% had a postregistration counselling qualification, and about a quarter were based in hospitals. The average caseload size was 61 and the service was predominantly a closed referral one. The main client care activities were: assessment of clients, medication management, health promotion, and client and family support. From the observations, there was no evidence of CPNs practising cognitive, behaviour therapy or family therapies to any great extent. This study provides baseline data for monitoring trends in community mental health nursing in Ireland, and for informing future policy regarding service provision and training of CPNs. PMID- 17352782 TI - Transference in the nurse-patient relationship. AB - The therapeutic relationship has been considered foundational to psychiatric nursing practice since at least the mid-20th century. However, this does not, in itself, guarantee either its continuity or relevance to current practice. Concepts such as the therapeutic relationship require sustained attention, both in theory and in practice, to illustrate ongoing relevance to the discipline. This paper addresses the therapeutic relationship in psychiatric nursing via aspects of psychoanalytic theory, particularly the notion of transference, as theorized by both Freud and Lacan. Two case fragments provide practice material, through which transference in the nurse-patient relationship is explored. The nurse, in the context of his/her relationship with the patient, a sick stranger, offers both a listening and the potential development of transference. This transference can be experienced, in part, as a form of attachment to the nurse, one that is not regarded pejoratively as dependency. There is the potential, within the nurse-patient relationship, for a psychical holding to develop, one from within which both the patient can speak and transference might arise. It is argued that listening to the patient has the potential to assist the patient and, with the development of transference, can provide the context for important work. PMID- 17352783 TI - Surveying the attitudes of acute mental health nurses. AB - Recent UK policy and guidance indicates the importance of positive attitudes towards mental health service users. This is especially true in acute inpatient care, where service users are often at their most vulnerable and have higher levels of contact with mental health staff. The following paper details secondary analysis of data collected for the validation of an attitude measurement scale with a sample of 140 nursing staff in acute settings. The results demonstrate that a wide range of attitudes are held by mental health nurses towards acute mental health care. Overall, the results indicate generally positive attitudes. Significant differences were found between qualified and unqualified staff, and males and females for some questions. Recommendations are made for future attitudinal research of mental health staff. PMID- 17352785 TI - Adolescents coping with mood disorder: a grounded theory study. AB - A grounded theory methodology was used to explore the phenomenon of coping as experienced by adolescents with a mood disorder. Mood disorders among children and adolescents are more persistent than previously thought and have numerous negative associated features, including further episodes of depression, impaired social, academic and vocational relationships, use of alcohol and other drugs, and an increased risk of suicide. Current literature offered little awareness of how adolescents cope with a mood disorder, as well as their perspective of how such an illness impacts their lives. A substantive theory regarding the process of coping for adolescents with a mood disorder was generated from the data collected from one male and eight female adolescents. Using grounded theory coding procedures, a four-phase coping theory identified by the categories feeling different, cutting off connections, facing the challenge/reconnecting, and learning from the experience was developed. The core category identified in this research was An Unplanned Journey: Coping Through Connections. Implications identified for nursing practice, research and education included greater attention on the prevention of adolescent mood disorder, and the education of adolescents about the development and enhancement of healthy coping skills. PMID- 17352784 TI - Early intervention in psychosis: a rural perspective. AB - Over the past decade, there has been great interest in both the development and delivery of early intervention in psychosis services in the United Kingdom, supported by national policy and a Policy Implementation Guide (PIG). Despite this, the PIG fails to distinguish the delivery of early intervention services to different population groups. The paper aims to augment available literature with the range of complex issues that practitioners may face when working in rural settings and link this to the development of early intervention services in rural communities. This paper will also outline some of the fundamental factors that challenge delivery of early intervention to individuals with a first episode of psychosis and their families in rural communities. Important key areas for consideration will be highlighted for both the planning and delivery of early intervention to rural communities. PMID- 17352787 TI - RT-PCR amplification and sequence analysis of extra small virus associated with white tail disease of Macrobrachium rosenbergii (de Man) cultured in Taiwan. AB - Post-larvae of Macrobrachium rosenbergii infected with white tail disease (WTD) have been reported in Taiwan. The causative agents have been identified as M. rosenbergii nodavirus (MrNV) associated with extra small virus (XSV). The present study is the first report confirming the presence of XSV virus in M. rosenbergii displaying WTD symptoms in Taiwan by reverse transcription polymerase chain reaction (RT-PCR). A 772 bp amplified product was obtained by RT-PCR, cloned and sequenced. The nucleotide sequence analysis of the 772 bp DNA fragment revealed 98% and 97% identity with XSV isolated from China and India, respectively. Comparison of the deduced amino acid sequences of the XSV partial genome showed strong homology (99% and 97%) with isolates from China and India. Phylogenetic analysis revealed the XSV-Taiwan isolate was more closely related to the Chinese rather than the Indian isolates. The results demonstrated the presence of XSV virus co-infection in M. rosenbergii cultured in Taiwan suffering from WTD. PMID- 17352788 TI - A reovirus disease in cultured mud crab, Scylla serrata, in southern China. AB - A reovirus, designated mud crab reovirus (MCRV), associated with large economic losses was recently isolated from marine cultured mud crab, Scylla serrata, in southern China. The complete viral particle is 70 nm in diameter, icosahedral and non-enveloped. The virus infects connective tissue cells of the hepatopancreas, gills and intestine in mud crab and develops in the cytoplasm. Hundred per cent mortality was observed in mud crab experimentally infected by intramuscular injection, bath inoculation and oral inoculation, while cohabitation infection caused 80% mortality. The viral genome consists of 13 linear dsRNA segments, with an electrophoretic pattern 1/5/7. The results of this study suggest that the virus is highly pathogenic and can be transmitted enterically as well as via the body surface of mud crab. Although the genomic organization of this virus is different from that of the other crab reoviruses, CcRV-W2 and DpPV, all three of these reoviruses have similar electrophoresis patterns. Therefore, MCRV may be a new member of the DpPV and CcRV-W2 group. PMID- 17352789 TI - PCR-RFLP genotypes associated with quinolone resistance in isolates of Flavobacterium psychrophilum. AB - A novel genotyping method for epizootiological studies of bacterial cold-water disease caused by Flavobacterium psychrophilum and associated with quinolone resistance was developed. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) was performed on 244 F. psychrophilum isolates from various fish species. PCR was performed with primer pair GYRA-FP1F and GYRA-FP1R amplifying the A subunit of the DNA gyrase (GyrA) gene, which contained the quinolone resistance determining region. Digestion of PCR products with the restriction enzyme Mph1103I showed two genotypes, QR and QS. The difference between these genotypes was amino acid substitutions at position 83 of GyrA (Escherichia coli numbering). The genotype QR indicated an alanine residue at this position associated with quinolone resistance in F. psychrophilum isolates. Of the 244 isolates tested in this study, the number of QR genotype isolates was 153 (62.7%). In isolates from ayu (n=177), 146 (82.5%) were genotype QR. With combination of this technique and previously reported PCR-RFLP genotyping, eight genotypes were observed in F. psychrophilum isolates. Using this genotyping system, the relationships between genotype and host fish species, or locality of isolation, were analysed and are discussed. PMID- 17352790 TI - The life cycle of Chloromyxum auratum (Myxozoa) from goldfish, Carassius auratus (L.), involves an antonactinomyxon actinospore. AB - The myxozoan parasite Chloromyxum auratumHallett, Atkinson, Holt, Banner & Bartholomew, 2006, was shown experimentally to have a two-host life cycle which involved a previously undescribed antonactinomyxon actinospore stage. Myxospores obtained from gall bladders of naturally infected feral goldfish, Carassius auratus (L.), were used to infect samples of mixed species of oligochaete worms obtained from the same locality as the fish: Fern Ridge Dam, Oregon, USA. After some 110 days post-exposure, actinospores were detected from the water above the oligochaetes. The 18S rDNA sequence of these actinospores was identical to the original myxospores. Spore release was sporadic, of low intensity and short duration, which confounded efforts to identify the host oligochaete species and infect naive fish. This is the first life cycle that incorporates an actinospore of the collective group Antonactinomyxon, and the first life cycle demonstrated in the laboratory for a species of Chloromyxum. PMID- 17352791 TI - Epidemiological observations of pancreas disease of farmed Atlantic salmon, Salmo salar L., in Ireland. AB - Epidemiological investigations into the pancreas disease (PD) of farmed salmon were conducted on populations of Atlantic salmon reared in Ireland during 2003 and 2004. The investigations surveyed all marine salmon farms operating in Ireland through a detailed questionnaire with follow-up farm visits. Information was gathered on 21 populations of fish in 2003 and 14 populations in 2004. Thirteen of the 21 populations suffered PD in 2003 and 12 of the 14 in 2004. The mean mortality due to PD on affected farms was 18.8% in 2003 and 14.8% in 2004 and the loss of growth due to PD was estimated at 11.4% over the 2-year period. The highest risk periods for outbreaks of PD were early summer and early autumn and the farms most seriously affected by PD mortality were in the western counties of Ireland. Factors which showed an indication of association with a PD outbreak or high mortality during a PD outbreak were: livestock movement to another sea site, high feeding rate prior to any PD outbreak, the presence of another PD positive farm in the same water body, greater than 250000 fish on a site, a previous history of PD on a site, a high sea lice burden, and sites located in the western regions of Ireland which reared a specific strain of salmon. PMID- 17352792 TI - Blue sac disease in larval whitefish, Coregonus lavaretus (L.): pathological changes in mRNA levels of CYP1A, ERalpha, and p53. PMID- 17352793 TI - Differentiating 16S rRNA alleles of Flavobacterium psychrophilum using a simple PCR assay. PMID- 17352794 TI - A roni-like virus associated with mortalities of the freshwater crab, Eriocheir sinensis Milne Edwards, cultured in China, exhibiting 'sighs disease' and black gill syndrome. PMID- 17352795 TI - Development of an in vivo assay to assess attachment of Neoparamoeba sp. (an amphizoic gymnamoeba) to the gills of Atlantic salmon, Salmo salar L. PMID- 17352796 TI - Case mix, outcomes and comparison of risk prediction models for admissions to adult, general and specialist critical care units for head injury: a secondary analysis of the ICNARC Case Mix Programme Database. AB - INTRODUCTION: This report describes the case mix and outcome (mortality, intensive care unit (ICU) and hospital length of stay) for admissions to ICU for head injury and evaluates the predictive ability of five risk adjustment models. METHODS: A secondary analysis was conducted of data from the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme, a high quality clinical database, of 374,594 admissions to 171 adult critical care units across England, Wales and Northern Ireland from 1995 to 2005. The discrimination and calibration of five risk prediction models, SAPS II, MPM II, APACHE II and III and the ICNARC model plus raw Glasgow Coma Score (GCS) were compared. RESULTS: There were 11,021 admissions following traumatic brain injury identified (3% of all database admissions). Mortality in ICU was 23.5% and in-hospital was 33.5%. Median ICU and hospital lengths of stay were 3.2 and 24 days, respectively, for survivors and 1.6 and 3 days, respectively, for non-survivors. The ICNARC model, SAPS II and MPM II discriminated best between survivors and non-survivors and were better calibrated than raw GCS, APACHE II and III in 5,393 patients eligible for all models. CONCLUSION: Traumatic brain injury requiring intensive care has a high mortality rate. Non-survivors have a short length of ICU and hospital stay. APACHE II and III have poorer calibration and discrimination than SAPS II, MPM II and the ICNARC model in traumatic brain injury; however, no model had perfect calibration. PMID- 17352797 TI - Dosage compensation is less effective in birds than in mammals. AB - BACKGROUND: In animals with heteromorphic sex chromosomes, dosage compensation of sex-chromosome genes is thought to be critical for species survival. Diverse molecular mechanisms have evolved to effectively balance the expressed dose of X linked genes between XX and XY animals, and to balance expression of X and autosomal genes. Dosage compensation is not understood in birds, in which females (ZW) and males (ZZ) differ in the number of Z chromosomes. RESULTS: Using microarray analysis, we compared the male:female ratio of expression of sets of Z linked and autosomal genes in two bird species, zebra finch and chicken, and in two mammalian species, mouse and human. Male:female ratios of expression were significantly higher for Z genes than for autosomal genes in several finch and chicken tissues. In contrast, in mouse and human the male:female ratio of expression of X-linked genes is quite similar to that of autosomal genes, indicating effective dosage compensation even in humans, in which a significant percentage of genes escape X-inactivation. CONCLUSION: Birds represent an unprecedented case in which genes on one sex chromosome are expressed on average at constitutively higher levels in one sex compared with the other. Sex chromosome dosage compensation is surprisingly ineffective in birds, suggesting that some genomes can do without effective sex-specific sex-chromosome dosage compensation mechanisms. PMID- 17352798 TI - Plasma nevirapine levels, adverse events and efficacy of antiretroviral therapy among HIV-infected patients concurrently receiving nevirapine-based antiretroviral therapy and fluconazole. AB - BACKGROUND: The clinical data of plasma NVP level, safety and efficacy of antiretroviral therapy (ART) for the concurrent use of nevirapine (NVP)-based ART and fluconazole (FLU) is scanty. METHODS: A retrospective study was conducted in patients who were initiated NVP-based ART between October 2004 and November 2005. The objectives were to compare NVP levels, adverse events, and 36-week efficacy of NVP-based ART between patients who did not receive FLU (group A) and those who received FLU 200 mg/day or 400 mg/day (group B). RESULTS: There were 122 patients with mean +/- SD age of 36 +/- 9 years; 81 in group A and 41 in group B. Median (IQR) baseline CD4 cell count was 29 (8-79) cell/mm3 in group A and 19 (8-33) cell/mm3 in group B (P = 0.102). Baseline characteristics between the two groups were similar. Mean +/- SD NVP levels were 6.5 +/- 3.0 mg/L in group A and 11.4 +/ 6.1 mg/L in group B(P < 0.001). One (2.4%) patient in group B developed clinical hepatitis (P = 0.336). Six (7.4%) patients in group A developed NVP-related skin rashes (P = 0.096). There were no differences in term of 36-week antiviral efficacy between the two groups (P > 0.05). CONCLUSION: Co-administration of NVP and daily dosage of FLU (200 mg/day and 400 mg/day) results in markedly increased trough plasma NVP level when compared to the administration of NVP alone. The concurrent use of NVP and FLU in very advanced HIV-infected patients is well tolerated. The immunological and virological responses are favorable. PMID- 17352800 TI - Severe upper airway obstruction due to delayed retropharyngeal hematoma formation following blunt cervical trauma. AB - BACKGROUND: We report a case of severe upper airway obstruction due to a retropharyngeal hematoma that presented nearly one day after a precipitating traumatic injury. Retropharyngeal hematomas are rare, but may cause life threatening airway compromise. CASE PRESENTATION: A 50 year-old man developed severe dyspnea with oropharyngeal airway compression due to retropharyngeal hematoma 20 hours after presenting to the emergency department. The patient also had a fractured first cervical vertebra and was diagnosed with a left brachial plexopathy. The patient underwent emergent awake fiberoptic endotracheal intubation to provide a definitive airway. CONCLUSION: Retropharyngeal hematoma with life-threatening airway compromise can develop hours or days after a precipitating injury. Clinicians should be alert to the potential for this delayed airway collapse, and should also be prepared to rapidly secure the airway in this patient population likely to have concomitant cervical spinal or head injuries. PMID- 17352799 TI - Genome analysis of DNA repair genes in the alpha proteobacterium Caulobacter crescentus. AB - BACKGROUND: The integrity of DNA molecules is fundamental for maintaining life. The DNA repair proteins protect organisms against genetic damage, by removal of DNA lesions or helping to tolerate them. DNA repair genes are best known from the gamma-proteobacterium Escherichia coli, which is the most understood bacterial model. However, genome sequencing raises questions regarding uniformity and ubiquity of these DNA repair genes and pathways, reinforcing the need for identifying genes and proteins, which may respond to DNA damage in other bacteria. RESULTS: In this study, we employed a bioinformatic approach, to analyse and describe the open reading frames potentially related to DNA repair from the genome of the alpha-proteobacterium Caulobacter crescentus. This was performed by comparison with known DNA repair related genes found in public databases. As expected, although C. crescentus and E. coli bacteria belong to separate phylogenetic groups, many of their DNA repair genes are very similar. However, some important DNA repair genes are absent in the C. crescentus genome and other interesting functionally related gene duplications are present, which do not occur in E. coli. These include DNA ligases, exonuclease III (xthA), endonuclease III (nth), O6-methylguanine-DNA methyltransferase (ada gene), photolyase-like genes, and uracil-DNA-glycosylases. On the other hand, the genes imuA and imuB, which are involved in DNA damage induced mutagenesis, have recently been described in C. crescentus, but are absent in E. coli. Particularly interesting are the potential atypical phylogeny of one of the photolyase genes in alpha-proteobacteria, indicating an origin by horizontal transfer, and the duplication of the Ada orthologs, which have diverse structural configurations, including one that is still unique for C. crescentus. CONCLUSION: The absence and the presence of certain genes are discussed and predictions are made considering the particular aspects of the C. crescentus among other known DNA repair pathways. The observed differences enlarge what is known for DNA repair in the Bacterial world, and provide a useful framework for further experimental studies in this organism. PMID- 17352801 TI - Computer simulation allows goal-oriented mechanical ventilation in acute respiratory distress syndrome. AB - INTRODUCTION: To prevent further lung damage in patients with acute respiratory distress syndrome (ARDS), it is important to avoid overdistension and cyclic opening and closing of atelectatic alveoli. Previous studies have demonstrated protective effects of using low tidal volume (VT), moderate positive end expiratory pressure and low airway pressure. Aspiration of dead space (ASPIDS) allows a reduction in VT by eliminating dead space in the tracheal tube and tubing. We hypothesized that, by applying goal-orientated ventilation based on iterative computer simulation, VT can be reduced at high respiratory rate and much further reduced during ASPIDS without compromising gas exchange or causing high airway pressure. METHODS: ARDS was induced in eight pigs by surfactant perturbation and ventilator-induced lung injury. Ventilator resetting guided by computer simulation was then performed, aiming at minimal VT, plateau pressure 30 cmH2O and isocapnia, first by only increasing respiratory rate and then by using ASPIDS as well. RESULTS: VT decreased from 7.2 +/- 0.5 ml/kg to 6.6 +/- 0.5 ml/kg as respiratory rate increased from 40 to 64 +/- 6 breaths/min, and to 4.0 +/- 0.4 ml/kg when ASPIDS was used at 80 +/- 6 breaths/min. Measured values of arterial carbon dioxide tension were close to predicted values. Without ASPIDS, total positive end-expiratory pressure and plateau pressure were slightly higher than predicted, and with ASPIDS they were lower than predicted. CONCLUSION: In principle, computer simulation may be used in goal-oriented ventilation in ARDS. Further studies are needed to investigate potential benefits and limitations over extended study periods. PMID- 17352802 TI - CAALYX: a new generation of location-based services in healthcare. AB - Recent advances in mobile positioning systems and telecommunications are providing the technology needed for the development of location-aware tele-care applications. This paper introduces CAALYX--Complete Ambient Assisted Living Experiment, an EU-funded project that aims at increasing older people's autonomy and self-confidence by developing a wearable light device capable of measuring specific vital signs of the elderly, detecting falls and location, and communicating automatically in real-time with his/her care provider in case of an emergency, wherever the older person happens to be, at home or outside. PMID- 17352803 TI - Infection by the hepatitis C virus in chronic renal failure patients undergoing hemodialysis in Mato Grosso state, central Brazil: a cohort study. AB - BACKGROUND: Hepatitis C virus (HCV) is a significant problem for patients undergoing hemodialysis therapy. This situation has never been studied in Mato Grosso state, central Brazil. This study was conducted aiming to estimate the prevalence of the anti-HCV and the incidence of seroconversion in the main metropolitan region of the state. METHODS: 433 patients from the six hemodialysis units were interviewed and anti-HCV was tested by a third-generation enzyme immunoassay. An open cohort of patients who tested negative for anti-HCV at the entry of the study was created and seroconversions was assessed monthly. The staff responsible for the units were interviewed to assess whether the infection control measures were being followed. Logistic and Cox regression analysis were performed in order to assess risk factor to HCV. RESULTS: The entry on the study took place between January 2002 and June 2005. 73 out of 433 (16.9%, CI 95%: 13.3 20.8) was found to be anti-HCV reactive. The multivariate analysis indicated as risk factors associated to anti-HCV the duration of the hemodialysis treatment, the number of transfusions received, and the unit of treatment. An open cohort of 360 patients who tested negative for anti-HCV was created, with a following average of 24 (+/- 15) months. Forty seroconversions were recorded corresponding to an incidence density of 4.6/1000 patient-months, ranges 0 to 30 among the units. Cox regression indicated the time of hemodialysis (RR = 2.2; CI 95%: 1.1 4.6; p < 0.05) and the unit where treatment was performed (RR = 42.4; CI 95%: 9.9 180.5; p < 0.05) as risk factors for seroconversion. The three units with highest anti-HCV prevalence and incidence were identified as those that more frequently failed to apply control measures. CONCLUSION: The study demonstrated high prevalence and incidence of anti-HCV in some of the hemodialysis units. Time on hemodialysis therapy was an independent factor associated to HCV. Blood transfusion was associated with anti-HCV in initial survey but was not important in incident cases. Failure of applying control measures was more evident in units with the highest HCV prevalence and incidence. The results suggest that nosocomial transmission was the main spread factor of HCV in the studied population. PMID- 17352804 TI - Transcriptional activation of the human papillomavirus type 5 and 16 long control region in cells from cutaneous and mucosal origin. AB - Human papillomavirus type-16 (HPV-16) infects mucosal epithelium and is the most common type found in cervical cancer. HPV-5 infects cornified epithelium and is the most common type found on normal skin and belongs to the types frequently associated with skin cancers of Epidermodysplasia verruciformis patients. One factor by which this anatomical tropism could be determined is the regulation of HPV gene expression in the host cell. The HPV long control region (LCR) contains cis-responsive elements that regulate HPV transcription and the epithelial tropism of HPV is determined by epithelial specific constitutive enhancers in the LCR. Since HPV-16 and other types infecting the mucosa differ in host cell from HPV types infecting skin, it has been hypothesized that it is the combination of ubiquitous transcription factors working in concert in the host cell that determines the cell-type-specific expression. To study if HPV tropism could be determined by differences in transcriptional regulation we have cloned the transcriptional regulating region, LCR, from HPV-16 and HPV-5 and studied the activation of a reporter gene in cell lines with different origin. To analyse promoter activity we transfected the plasmids into four different cell lines; HaCaT, C33A, NIKS and W12E and the efficiency of HPV-5 and HPV-16 LCR in the different cell lines was compared. In HaCaT cells, with a skin origin, the HPV-5 LCR was two-fold more efficient in transcriptional activation compared to the HPV 16 LCR. In cervical W12E cells the HPV-16 LCR was almost 2-fold more effective in activating transcription compared to the HPV-5 LCR. The ability to initiate transcription in the other cell lines was independent on cell origin and HPV type. PMID- 17352805 TI - Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial). AB - BACKGROUND: Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. METHODS/DESIGN: Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). DISCUSSION: The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor. PMID- 17352806 TI - Artesunate--amodiaquine combination therapy for falciparum malaria in young Gabonese children. AB - BACKGROUND: Artesunate-amodiaquine combination for the treatment of childhood malaria is one of the artemisinin combination therapies (ACTs) recommended by National authorities in many African countries today. Effectiveness data on this combination in young children is scarce. METHODS: The effectiveness of three daily doses of artesunate plus amodiaquine combination given unsupervised (n = 32), compared with the efficacy when given under full supervision (n = 29) to children with falciparum malaria were assessed in an unrandomized study. RESULTS: 61 patients analysed revealed a PCR-corrected day-28 cure rate of 86 % (25 of 29 patients; CI 69-95 %) in the supervised group and 63 % (20 of 32 patients; CI 45 77 %) in the unsupervised group. The difference in outcome between both groups was statistically significant (p = 0.04). No severe adverse events were reported. CONCLUSION: The effectiveness of this short course regimen in young children with falciparum malaria could be augmented by increased adherence and improved formulation. PMID- 17352807 TI - New genes in the evolution of the neural crest differentiation program. AB - BACKGROUND: Development of the vertebrate head depends on the multipotency and migratory behavior of neural crest derivatives. This cell population is considered a vertebrate innovation and, accordingly, chordate ancestors lacked neural crest counterparts. The identification of neural crest specification genes expressed in the neural plate of basal chordates, in addition to the discovery of pigmented migratory cells in ascidians, has challenged this hypothesis. These new findings revive the debate on what is new and what is ancient in the genetic program that controls neural crest formation. RESULTS: To determine the origin of neural crest genes, we analyzed Phenotype Ontology annotations to select genes that control the development of this tissue. Using a sequential blast pipeline, we phylogenetically classified these genes, as well as those associated with other tissues, in order to define tissue-specific profiles of gene emergence. Of neural crest genes, 9% are vertebrate innovations. Our comparative analyses show that, among different tissues, the neural crest exhibits a particularly high rate of gene emergence during vertebrate evolution. A remarkable proportion of the new neural crest genes encode soluble ligands that control neural crest precursor specification into each cell lineage, including pigmented, neural, glial, and skeletal derivatives. CONCLUSION: We propose that the evolution of the neural crest is linked not only to the recruitment of ancestral regulatory genes but also to the emergence of signaling peptides that control the increasingly complex lineage diversification of this plastic cell population. PMID- 17352808 TI - Repetitive DNA is associated with centromeric domains in Trypanosoma brucei but not Trypanosoma cruzi. AB - BACKGROUND: Trypanosomes are parasitic protozoa that diverged early from the main eukaryotic lineage. Their genomes display several unusual characteristics and, despite completion of the trypanosome genome projects, the location of centromeric DNA has not been identified. RESULTS: We report evidence on the location and nature of centromeric DNA in Trypanosoma cruzi and Trypanosoma brucei. In T. cruzi, we used telomere-associated chromosome fragmentation and found that GC-rich transcriptional 'strand-switch' domains composed predominantly of degenerate retrotranposons are a shared feature of regions that confer mitotic stability. Consistent with this, etoposide-mediated topoisomerase-II cleavage, a biochemical marker for active centromeres, is concentrated at these domains. In the 'megabase-sized' chromosomes of T. brucei, topoisomerase-II activity is also focused at single loci that encompass regions between directional gene clusters that contain transposable elements. Unlike T. cruzi, however, these loci also contain arrays of AT-rich repeats stretching over several kilobases. The sites of topoisomerase-II activity on T. brucei chromosome 1 and T. cruzi chromosome 3 are syntenic, suggesting that centromere location has been conserved for more than 200 million years. The T. brucei intermediate and minichromosomes, which lack housekeeping genes, do not exhibit site-specific accumulation of topoisomerase II, suggesting that segregation of these atypical chromosomes might involve a centromere-independent mechanism. CONCLUSION: The localization of centromeric DNA in trypanosomes fills a major gap in our understanding of genome organization in these important human pathogens. These data are a significant step towards identifying and functionally characterizing other determinants of centromere function and provide a framework for dissecting the mechanisms of chromosome segregation. PMID- 17352809 TI - Combination of surgical excision and custom designed silicon pressure splint therapy for keloids on the helical rim. AB - Keloids are defined as dermal fibrotic lesions which are considered an aberration of the wound healing process. Their etiology and pathogenesis are poorly understood. Different treatment modalities are described in the literature depending on the morphology and size of the keloid. We report a case of a large ear keloid on the helical rim which was successfully treated with surgery and a custom designed silicon pressure clip. PMID- 17352810 TI - "A free thenar flap--a case report". AB - We present a case report of a free thenar flap surgery done for a volar right hand middle finger, distal and middle phalanx degloving injury. A free thenar flap is a fasciocutaneous sensate flap supplied by a constant branch of the superficial radial artery and its variable nerve supply. It has a distinct advantage of low donor site morbidity, better cosmesis and texture of the flap. No immobilization is required postop. The donor site can be closed primarily. PMID- 17352811 TI - Feeding oxidized fat during pregnancy up-regulates expression of PPARalpha responsive genes in the liver of rat fetuses. AB - BACKGROUND: Feeding oxidized fats causes activation of peroxisome proliferator activated receptor alpha (PPARalpha) in the liver of rats. However, whether feeding oxidized fat during pregnancy also results in activation of PPARalpha in fetal liver is unknown. Thus, this study aimed to explore whether feeding oxidized fat during pregnancy causes a PPARalpha response in fetal liver. Two experiments with pregnant rats which were administered three different diets (control; oxidized fat; clofibrate as positive control) in a controlled feeding regimen during either late pregnancy (first experiment) or whole pregnancy (second experiment) were performed. RESULTS: In both experiments pregnant rats treated with oxidized fat or clofibrate had higher relative mRNA concentrations of the PPARalpha-responsive genes acyl-CoA oxidase (ACO), cytochrome P450 4A1 (CYP4A1), L-type carnitin-palmitoyl transferase I (L-CPT I), medium-chain acyl CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) in the liver than control rats (P < 0.05). In addition, in both experiments fetuses of the oxidized fat group and the clofibrate group also had markedly higher relative mRNA concentrations of ACO, CYP4A1, CPT I, MCAD, and LCAD in the liver than those of the control group (P < 0.05), whereas the relative mRNA concentrations of PPARalpha, SREBP-1c, and FAS did not differ between treatment groups. In the second experiment treatment with oxidized fat also reduced triacylglycerol concentrations in the livers of pregnant rats and fetuses (P < 0.05). CONCLUSION: The present study demonstrates for the first time that components of oxidized fat with PPARalpha activating potential are able to induce a PPARalpha response in the liver of fetuses. Moreover, the present study shows that feeding oxidized fat during whole pregnancy, but not during late pregnancy, lowers triacylglycerol concentrations in fetal livers. PMID- 17352812 TI - Density of dopaminergic fibres in the prefrontal cortex of gerbils is sensitive to aging. AB - Mesencephalic dopamine (DA) projections are essential for cognitive and behavioral functions and believed to play a critical role during development and aging. The dopaminergic afferents of the rodent prefrontal cortex (PFC) show an extremely prolonged maturation which is very sensitive to epigenetic challenges. However, less is known about the long-term maturation and aging of these DA axons. Therefore, immunohistochemically stained DA fibres were quantitatively examined in the PFC of the Mongolian gerbil (Meriones unguiculatus) ranging from 6 to 24 months of age. Results show a decrease in DA fibre densities in the superficial layers of the PFC in 24 month old animals compared to 6 and 12 months. PMID- 17352813 TI - Genetical genomics: use all data. AB - BACKGROUND: Genetical genomics is a very powerful tool to elucidate the basis of complex traits and disease susceptibility. Despite its relevance, however, statistical modeling of expression quantitative trait loci (eQTL) has not received the attention it deserves. Based on two reasonable assertions (i) a good model should consider all available variables as potential effects, and (ii) gene expressions are highly interconnected, we suggest that an eQTL model should consider the rest of expression levels as potential regressors, in addition to the markers. RESULTS: It is shown that power can be increased with this strategy. We also show, using classical statistical and support vector machines techniques in a reanalysis of public data, that the external transcripts, i.e., transcripts other than the one being analysed, explain on average much more variability than the markers themselves. The presence of eQTL hotspots is reassessed in the light of these results. CONCLUSION: Model choice is a critical yet neglected issue in genetical genomics studies. Although we are far from having a general strategy for model choice in this area, we can at least propose that any transcript level is scanned not only for the markers genotyped but also for the rest of gene expression levels. Some sort of stepwise regression strategy can be used to select the final model. PMID- 17352814 TI - Quantitative and qualitative differences in subcutaneous adipose tissue stores across lipodystrophy types shown by magnetic resonance imaging. AB - BACKGROUND: Lipodystrophies are characterized by redistributed subcutaneous fat stores. We previously quantified subcutaneous fat by magnetic resonance imaging (MRI) in the legs of two patients with familial partial lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3, respectively). We now extend the MRI analysis across the whole body of patients with different forms of lipodystrophy. METHODS: We studied five subcutaneous fat stores (supraclavicular, abdominal, gluteal, thigh and calf) and the abdominal visceral fat stores in 10, 2, 1, 1 and 2 female subjects with, respectively, FPLD2, FPLD3, HIV-related partial lipodystrophy (HIVPL), acquired partial lipodystrophy (APL), congenital generalized lipodystrophy (CGL) and in six normal control subjects. RESULTS: Compared with normal controls, FPLD2 subjects had significantly increased supraclavicular fat, with decreased abdominal, gluteal, thigh and calf subcutaneous fat. FPLD3 subjects had increased supraclavicular and abdominal subcutaneous fat, with less severe reductions in gluteal, thigh and calf fat compared to FPLD2 subjects. The repartitioning of fat in the HIVPL subject closely resembled that of FPLD3 subjects. APL and CGL subjects had reduced upper body, gluteal and thigh subcutaneous fat; the APL subject had increased, while CGL subjects had decreased subcutaneous calf fat. Visceral fat was markedly increased in FPLD2 and APL subjects. CONCLUSION: Semi automated MRI-based adipose tissue quantification indicates differences between various lipodystrophy types in these studied clinical cases and is a potentially useful tool for extended quantitative phenomic analysis of genetic metabolic disorders. Further studies with a larger sample size are essential for confirming these preliminary findings. PMID- 17352815 TI - Association between CFL1 gene polymorphisms and spina bifida risk in a California population. AB - BACKGROUND: CFL1 encodes human non-muscle cofilin (n-cofilin), which is an actin depolymerizing factor and is essential in cytokinesis, endocytosis, and in the development of all embryonic tissues. Cfl1 knockout mice exhibit failure of neural tube closure at E10.5 and die in utero. We hypothesized that genetic variation within the human CFL1 gene may alter the protein's function and result in defective actin depolymerizing and cellular activity during neural tube closure. Such alterations may be associated with an increased risk for neural tube defects (NTDs). METHODS: Having re-sequenced the human CFL1 gene and identified five common single nucleotide polymorphisms (SNPs) in our target population, we investigated whether there existed a possible association between the genetic variations of the CFL1 gene and risk of spina bifida. Samples were obtained from a large population-based case-control study in California. Allele association, genotype association and haplotype association were evaluated in two different ethnicity groups, non-Hispanic white and Hispanic white. RESULTS: Homozygosity for the minor alleles of the SNPs studied (rs652021, rs665306, rs667555, rs4621 and rs11227332) appeared to produce an increased risk for spina bifida. Subjects with the haplotype composed of all minor alleles (CCGGT) appeared to have increased spina bifida risk (OR = 1.6, 95% CI: 0.9~2.9), however, this finding is not statistically significant likely due to limited sample size. CONCLUSION: The sequence variation of human CFL1 gene is a genetic modifier for spina bifida risk in this California population. PMID- 17352816 TI - The cause of urinary symptoms among Human T Lymphotropic Virus Type I (HLTV-I) infected patients: a cross sectional study. AB - BACKGROUND: HTLV-I infected patients often complain of urinary symptomatology. Epidemiological studies have suggested that these individuals have a higher prevalence and incidence of urinary tract infection (UTI) than seronegative controls. However, the diagnosis of UTI in these studies relied only on patient information and did not require confirmation by urine culture. The purpose of this study was to investigate the role of urinary tract infection (UTI) as the cause of urinary symptoms in HTLV-I infected patients. METHODS: In this cross sectional study we interviewed, and cultured urine from, 157 HTLV-I seropositive individuals followed regularly at a specialized clinic. All patients were evaluated by a neurologist and classified according to the Expanded Disability Status Scale (EDSS). Urodynamic studies were performed at the discretion of the treating physician. RESULTS: Sixty-four patients complained of at least one active urinary symptom but UTI was confirmed by a positive urine culture in only 12 of these patients (19%); the majority of symptomatic patients (81%) had negative urine cultures. To investigate the mechanism behind the urinary complaints in symptomatic individuals with negative urine cultures, we reviewed the results of urodynamic studies performed in 21 of these patients. Most of them (90.5%) had abnormal findings. The predominant abnormalities were detrusor sphincter hyperreflexia and dyssynergia, findings consistent with HTLV-I-induced neurogenic bladder. On a multivariate logistic regression, an abnormal EDSS score was the strongest predictor of urinary symptomatology (OR 9.87, 95% CI 3.465 to 28.116, P < 0.0001). CONCLUSION: Urinary symptomatology suggestive of UTI is highly prevalent among HTLV-I seropositive individuals but true UTI is responsible for the minority of cases. We posit that the main cause of urinary symptoms in this population is neurogenic bladder. Our data imply that HLTV-I infected patients with urinary symptomatology should not be empirically treated for UTI but rather undergo urine culture; if a UTI is excluded, further investigation with urodynamic studies should be considered. PMID- 17352817 TI - Examination of program exposure across intervention delivery modes: face-to-face versus internet. AB - BACKGROUND: There has been increasing interest in the ability of the internet to produce behaviour change. The focus of this study was to describe program exposure across three intervention groups from a randomised trial (RT) comparing traditional face-to-face, internet-mediated (combined internet plus face-to face), and internet-only program delivery. METHODS: Baseline and immediately post intervention survey data, and exposure rates from participants that commenced the RT were included (n = 192). Exposure was defined as either face-to-face attendance, website usage, or a combination of both for the internet-mediated group. Characteristics of participants who were exposed to at least 75% of the program material were explored. Descriptive analysis and logistical regression were used to examine differences between groups for program exposure. RESULTS: All groups showed decrease in program exposure over time. Differences were also observed (chi2 = 10.37, p < 0.05), between intervention groups. The internet mediated (OR = 2.4, 95% CI 1.13-5.1) and internet-only (OR = 2.96, 95% CI 1.38 6.3) groups were more likely to have been exposed to at least 75% of the program compared to the face-to-face group. Participants with high physical activity self efficacy were 1.82 (95% CI 1.15-2.88) times more likely to have been exposed to 75% of the program, and those allocated to the face-to-face group were less likely to have attended 75% of the face-to-face sessions if they were classified as obese (OR = 0.21 95% CI 0.04-0.96). CONCLUSION: These results suggest that the internet groups were as effective as the face-to-face delivery mode in engaging participants in the program material. However, different delivery methods may be more useful to different sub-populations. It is important to explore which target groups that internet-based programs are best suited, in order to increase their impact. PMID- 17352818 TI - Pulsed-field gel electrophoresis profile homogeneity of Mycobacterium avium subsp. paratuberculosis isolates from cattle and heterogeneity of those from sheep and goats. AB - BACKGROUND: Mycobacterium avium subsp. paratuberculosis (Map) causes paratuberculosis in animals and is suspected of causing Crohn's Disease in humans. Characterization of strains led to classify paratuberculosis isolates in two main types, cattle type strains, found affecting all host species, and sheep type strains, reported affecting mainly sheep. In order to get a better understanding of the epidemiology of paratuberculosis a large set of Map isolates obtained from different species over the last 25 years have been characterized. Five-hundred and twenty isolates from different hosts (cattle, sheep, goats, bison, deer and wild boar) and origins had been cultured and typed by IS1311 restriction-endonuclease-analysis. Two-hundred and sixty-nine isolates were further characterized by pulsed-field gel electrophoresis (PFGE) using SnaBI and SpeI endonucleases. Differences in strain isolation upon various media conditions were also studied. RESULTS: All bovines, 4 and 26% of Spanish sheep and goats, respectively, and the deer and wild boar studied, carried IS1311-Cattle type strains. IS1311-Sheep type encompassed 96% and 74% of Spanish sheep and goats, and all three Portuguese sheep. Thirty-seven distinct multiplex PFGE profiles were found, giving 32 novel profiles. Profiles 2-1 and 1-1 accounted for the 85% of cattle isolates. Ten distinct profiles were detected in Spanish sheep, none of them with an incidence higher than 25%. Profile 16-11 (43%) and another three profiles were identified in Spanish caprine cultures. The hierarchical analysis, clustered all profiles found in cattle, "wild" hosts and some small ruminants within the same group. The other group included 11 profiles only found in Spanish sheep and goats, including Spanish pigmented profiles. Differences in growth requirements associated with isolate genotype were observed. CONCLUSION: Cattle in Spain are infected with cattle type strains, while sheep and goats are mainly infected with sheep type strains. Although 7H9 broth based culture media seem to broadly cover the growth requirements of most Map strains, the use of various solid media is recommended to reduce any recovery biases. High genetic homogeneity of isolates from cattle, and heterogeneity of those from sheep and goats have been detected. PMID- 17352819 TI - Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens. AB - BACKGROUND: Natural antibodies directed at carbohydrates reject porcine xenografts. They are initially expressed in germline configuration and are encoded by a small number of structurally-related germline progenitors. The transplantation of genetically-modified pig organs prevents hyperacute rejection, but delayed graft rejection still occurs, partly due to humoral responses. IgVH genes encoding induced xenoantibodies are predominantly, not exclusively, derived from germline progenitors in the VH3 family. We have previously identified the immunoglobulin heavy chain genes encoding VH3 xenoantibodies in patients and primates. In this manuscript, we complete the structural analysis of induced xenoantibodies by identifying the IgVH genes encoding the small proportion of VH4 xenoantibodies and the germline progenitors encoding xenoantibody light chains. This information has been used to define the xenoantibody/carbohydrate binding site using computer-simulated modeling. RESULTS: The VH4-59 gene encodes antibodies in the VH4 family that are induced in human patients mounting active xenoantibody responses. The light chain of xenoantibodies is encoded by DPK5 and HSIGKV134. The structural information obtained by sequencing analysis was used to create computer-simulated models. Key contact sites for xenoantibody/carbohydrate interaction for VH3 family xenoantibodies include amino acids in sites 31, 33, 50, 57, 58 and the CDR3 region of the IgVH gene. Site-directed mutagenesis indicates that mutations in predicted contact sites alter binding to carbohydrate xenoantigens. Computer-simulated modeling suggests that the CDR3 region directly influences binding. CONCLUSION: Xenoantibodies induced during early and delayed xenograft responses are predominantly encoded by genes in the VH3 family, with a small proportion encoded by VH4 germline progenitors. This restricted group can be identified by the unique canonical structure of the light chain, heavy chain and CDR3. Computer-simulated models depict this structure with accuracy, as confirmed by site-directed mutagenesis. Computer-simulated drug design using computer-simulated models may now be applied to develop new drugs that may enhance the survival of xenografted organs. PMID- 17352821 TI - Mid-term echocardiographic follow up of left ventricular function with permanent right ventricular pacing in pediatric patients with and without structural heart disease. AB - BACKGROUND: Chronic right ventricular apical pacing may have detrimental effect on left ventricular function and may promote to heart failure in adult patients with left ventricular dysfunction. METHODS: A group of 99 pediatric patients with previously implanted pacemaker was studied retrospectively. Forty-three patients (21 males) had isolated congenital complete or advanced atrioventricular block. The remaining 56 patients (34 males) had pacing indication in the presence of structural heart disease. Thirty-two of them (21 males) had isolated structural heart disease and the remaining 24 (13 males) had complex congenital heart disease. Patients were followed up for an average of 53 +/- 41.4 months with 12 lead electrocardiogram and transthoracic echocardiography. Left ventricular shortening fraction was used as a marker of ventricular function. QRS duration was assessed using leads V5 or II on standard 12-lead electrocardiogram. RESULTS: Left ventricular shortening fraction did not change significantly after pacemaker implantation compared to preimplant values overall and in subgroups. In patients with complex congenital heart malformations shortening fraction decreased significantly during the follow up period. (0.45 +/- 0.07 vs 0.35 +/- 0.06, p = 0.015). The correlation between the change in left ventricular shortening fraction and the mean increase of paced QRS duration was not significant. Six patients developed dilated cardiomyopathy, which was diagnosed 2 months to 9 years after pacemaker implantation. CONCLUSION: Chronic right ventricular pacing in pediatric patients with or without structural heart disease does not necessarily result in decline of left ventricular function. In patients with complex congenital heart malformations left ventricular shortening fraction shows significant decrease. PMID- 17352820 TI - Cigarette smoke exposure inhibits extracellular MMP-2 (gelatinase A) activity in human lung fibroblasts. AB - BACKGROUND: Exposure to cigarette smoke is considered a major risk factor for the development of lung diseases, since its causative role has been assessed in the induction and maintenance of an inflamed state in the airways. Lung fibroblasts can contribute to these processes, due to their ability to produce proinflammatory chemotactic molecules and extracellular matrix remodelling proteinases. Among proteolytic enzymes, gelatinases A and B have been studied for their role in tissue breakdown and mobilisation of matrix-derived signalling molecules. Multiple reports linked gelatinase deregulation and overexpression to the development of inflammatory chronic lung diseases such as COPD. METHODS: In this study we aimed to determine variations in the gelatinolytic pattern of human lung fibroblasts (HFL-1 cell line) exposed to cigarette smoke extract (CSE). Gelatinolytic activity levels were determined by using gelatin zymography for the in-gel detection of the enzymes (proenzyme and activated forms), and the subsequent semi-quantitative densitometric evaluation of lytic bands. Expression of gelatinases was evaluated also by RT-PCR, zymography of the cell lysates and by western blotting. RESULTS: CSE exposure at the doses used (1-10%) did not exert any significant cytotoxic effects on fibroblasts. Zymographic analysis showed that CSE exposure resulted in a linear decrease of the activity of gelatinase A. Control experiments allowed excluding a direct inhibitory effect of CSE on gelatinases. Zymography of cell lysates confirmed the expression of MMP-2 in all conditions. Semi-quantitative evaluation of mRNA expression allowed assessing a reduced transcription of the enzyme, as well as an increase in the expression of TIMP-2. Statistical analyses showed that the decrease of MMP-2 activity in conditioned media reached the statistical significance (p = 0.0031 for 24 h and p = 0.0012 for 48 h), while correlation analysis showed that this result was independent from CSE cytotoxicity (p = 0.7833 for both exposures). CONCLUSION: Present work describes for the first time that, apart well characterized proinflammatory responses, human lung fibroblasts may react to CSE with a significant reduction of extracellular MMP-2 lytic activity. Therefore, fibroblasts may actively participate to the alteration of the proteolysis/antiproteolysis balance, which reflects the defective repair of the extracellular matrix. Such event should provide a further contribution to the maintenance of the inflamed state in the lungs. PMID- 17352822 TI - Identification of a human TFPI-2 splice variant that is upregulated in human tumor tissues. AB - BACKGROUND: Previous studies have shown that the expression of tissue factor pathway inhibitor-2 (TFPI-2), a matrix-associated Kunitz-type serine proteinase inhibitor, is markedly down-regulated in several tumor cells through hypermethylation of the TFPI-2 gene promoter. In the present study, RT-PCR analysis of total RNA from both human normal and tumor cells revealed a novel 289 nucleotide splice variant of the TFPI-2 transcript designated as aberrantly spliced TFPI-2 (asTFPI-2). RESULTS: Nucleotide sequence analyses indicated that asTFPI-2 consists of complete exons II and V, fused with several nucleotides derived from exons III and IV, as well as six nucleotides derived from intron C. 5'- and 3'-RACE analyses of total RNA amplified exclusively the wild-type TFPI-2 transcript, indicating that asTFPI-2 lacks either a 5'-untranslated region (UTR) or a 3'-poly (A)+ tail. Quantitative real-time RT-PCR analyses revealed that several human tumor cells contain 4 to 50-fold more copies of asTFPI-2 in comparison to normal cells. In spite of the absence of a 5'-UTR or poly (A)+ tail, the asTFPI-2 variant exhibited a half-life of ~16 h in tumor cells. CONCLUSION: Our studies reveal the existence of a novel, aberrantly-spliced TFPI 2 transcript predominantly expressed in tumor cells and provides suggestive evidence for an additional mechanism for tumor cells to down-regulate TFPI-2 protein expression enhancing their ability to degrade the extracellular matrix. PMID- 17352824 TI - Behavioural and morphological evidence for the involvement of glial cell activation in delta opioid receptor function: implications for the development of opioid tolerance. AB - Previous studies have demonstrated that prolonged morphine treatment in vivo induces the translocation of delta opioid receptors (deltaORs) from intracellular compartments to neuronal plasma membranes and this trafficking event is correlated with an increased functional competence of the receptor. The mechanism underlying this phenomenon is unknown; however chronic morphine treatment has been shown to involve the activation and hypertrophy of spinal glial cells. In the present study we have examined whether activated glia may be associated with the enhanced deltaOR-mediated antinociception observed following prolonged morphine treatment. Accordingly, animals were treated with morphine with or without concomitant administration of propentofylline, an inhibitor of glial activation that was previously shown to block the development of morphine antinociceptive tolerance. The morphine regimen previously demonstrated to initiate deltaOR trafficking induced the activation of both astrocytes and microglia in the dorsal spinal cord as indicated by a significant increase in cell volume and cell surface area. Consistent with previous data, morphine treated rats displayed a significant augmentation in deltaOR-mediated antinociception. Concomitant spinal administration of propentofylline with morphine significantly attenuated the spinal immune response as well as the morphine-induced enhancement of deltaOR-mediated effects. These results complement previous reports that glial activation contributes to a state of opioid analgesic tolerance, and also suggest that neuro-glial communication is likely responsible in part for the altered functional competence in deltaOR mediated effects following morphine treatment. PMID- 17352823 TI - Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation. AB - BACKGROUND: Human mesenchymal stem cells (MSC) with the capacity to differentiate into osteoblasts provide potential for the development of novel treatment strategies, such as improved healing of large bone defects. However, their low frequency in bone marrow necessitate ex vivo expansion for further clinical application. In this study we asked if MSC are developing in an aberrant or unwanted way during ex vivo long-term cultivation and if artificial cultivation conditions exert any influence on their stem cell maintenance. To address this question we first developed human oligonucleotide microarrays with 30.000 elements and then performed large-scale expression profiling of long-term expanded MSC and MSC during differentiation into osteoblasts. RESULTS: The results showed that MSC did not alter their osteogenic differentiation capacity, surface marker profile, and the expression profiles of MSC during expansion. Microarray analysis of MSC during osteogenic differentiation identified three candidate genes for further examination and functional analysis: ID4, CRYAB, and SORT1. Additionally, we were able to reconstruct the three developmental phases during osteoblast differentiation: proliferation, matrix maturation, and mineralization, and illustrate the activation of the SMAD signaling pathways by TGF-beta2 and BMPs. CONCLUSION: With a variety of assays we could show that MSC represent a cell population which can be expanded for therapeutic applications. PMID- 17352825 TI - Association of West Nile virus illness and urban landscapes in Chicago and Detroit. AB - BACKGROUND: West Nile virus infection in humans in urban areas of the Midwestern United States has exhibited strong spatial clustering during epidemic years. We derived urban landscape classes from the physical and socio-economic factors hypothesized to be associated with West Nile Virus (WNV) transmission and compared those to human cases of illness in 2002 in Chicago and Detroit. The objectives were to improve understanding of human exposure to virus-infected mosquitoes in the urban context, and to assess the degree to which environmental factors found to be important in Chicago were also found in Detroit. RESULTS: Five urban classes that partitioned the urban space were developed for each city region. The classes had many similarities in the two settings. In both regions, the WNV case rate was considerably higher in the urban class associated with the Inner Suburbs, where 1940-1960 era housing dominates, vegetation cover is moderate, and population density is moderate. The land cover mapping approach played an important role in the successful and consistent classification of the urban areas. CONCLUSION: The analysis demonstrates how urban form and past land use decisions can influence transmission of a vector-borne virus. In addition, the results are helpful to develop hypotheses regarding urban landscape features and WNV transmission, they provide a structured method to stratify the urban areas to locate representative field study sites specifically for WNV, and this analysis contributes to the question of how the urban environment affects human health. PMID- 17352826 TI - Sociodemographic characteristics and diabetes predict invalid self-reported non smoking in a population-based study of U.S. adults. AB - BACKGROUND: Nearly all studies reporting smoking status collect self-reported data. The objective of this study was to assess sociodemographic characteristics and selected, common smoking-related diseases as predictors of invalid reporting of non-smoking. Valid self-reported smoking may be related to the degree to which smoking is a behavior that is not tolerated by the smoker's social group. METHODS: True smoking was defined as having serum cotinine of 15+ng/ml. 1483 "true" smokers 45+ years of age with self-reported smoking and serum cotinine data from the Mobile Examination Center were identified in the third National Health and Nutrition Examination Survey. Invalid non-smoking was defined as "true" smokers self-reporting non-smoking. To assess predictors of invalid self reported non-smoking, odds ratios (OR) and 95% confidence intervals (CI) were calculated for age, race/ethnicity-gender categories, education, income, diabetes, hypertension, and myocardial infarction. Multiple logistic regression modeling took into account the complex survey design and sample weights. RESULTS: Among smokers with diabetes, invalid non-smoking status was 15%, ranging from 0% for Mexican-American (MA) males to 22%-25% for Non-Hispanic White (NHW) males and Non-Hispanic Black (NHB) females. Among smokers without diabetes, invalid non smoking status was 5%, ranging from 3% for MA females to 10% for NHB females. After simultaneously taking into account diabetes, education, race/ethnicity and gender, smokers with diabetes (ORAdj = 3.15; 95% CI: 1.35-7.34), who did not graduate from high school (ORAdj = 2.05; 95% CI: 1.30-3.22) and who were NHB females (ORAdj = 5.12; 95% CI: 1.41-18.58) were more likely to self-report as non smokers than smokers without diabetes, who were high school graduates, and MA females, respectively. Having a history of myocardial infarction or hypertension did not predict invalid reporting of non-smoking. CONCLUSION: Validity of self reported non-smoking may be related to the relatively slowly progressing chronic nature of diabetes, in contrast with the acute event of myocardial infarction which could be considered a more serious, major life changing event. These data also raise questions regarding the possible role of societal desirability in the validity of self-reported non-smoking, especially among smokers with diabetes, who did not graduate from high school, and who were NHB females. PMID- 17352828 TI - A pilot study of IL-1 inhibition by anakinra in acute gout. AB - Monosodium urate crystals stimulate monocytes and macrophages to release IL-1beta through the NALP3 component of the inflammasome. The effectiveness of IL-1 inhibition in hereditary autoinflammatory syndromes with mutations in the NALP3 protein suggested that IL-1 inhibition might also be effective in relieving the inflammatory manifestations of acute gout. The effectiveness of IL-1 inhibition was first evaluated in a mouse model of monosodium urate crystal-induced inflammation. IL-1 inhibition prevented peritoneal neutrophil accumulation but TNF blockade had no effect. Based on these findings, we performed a pilot, open labeled study (trial registration number ISRCTN10862635) in 10 patients with gout who could not tolerate or had failed standard antiinflammatory therapies. All patients received 100 mg anakinra daily for 3 days. All 10 patients with acute gout responded rapidly to anakinra. No adverse effects were observed. IL-1 blockade appears to be an effective therapy for acute gouty arthritis. The clinical findings need to be confirmed in a controlled study. PMID- 17352827 TI - Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons. AB - Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases) in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon. The resulting mutant could still replicate, although at a reduced level. In addition, mutation A231C (also in motif A) yielded high levels of replication. Taken together these results show that poliovirus polymerase conserved residues D233 and A231 are not essential to poliovirus replicon function. PMID- 17352830 TI - Evaluation of a commercial Erns-capture ELISA for detection of BVDV in routine diagnostic cattle serum samples. AB - BACKGROUND: Bovine viral diarrhoea virus (BVDV) is an important pathogen in cattle. The ability of the virus to cross the placenta during early pregnancy can result in the birth of persistently infected (PI) calves. These calves shed the virus during their entire lifespan and are the key transmitters of infection. Consequently, identification (and subsequent removal) of PI animals is necessary to rapidly clear infected herds from the virus. The objective of this study was to evaluate the suitability of a commercial Erns-capture ELISA, in comparison to the indirect immunoperoxidase test (IPX), for routine diagnostic detection of BVDV within a control programme. In addition, the effect of passive immunity and heat-inactivation of the samples on the performance of the ELISA was studied. METHODS: In the process of virus clearance within the Swedish BVDV control programme, all calves born in infected herds are tested for virus and antibodies. From such samples, sent in for routine diagnostics to SVA, we selected 220 sera collected from 32 beef herds and 29 dairy herds. All sera were tested for BVDV antigen using the Erns ELISA, and the results were compared to the results from the IPX used within the routine diagnostics. RESULTS: All 130 samples categorized as virus negative by IPX were tested negative in the ELISA, and all 90 samples categorized as virus positive were tested positive, i.e. the relative sensitivity and specificity of the ELISA was 100% in relation to IPX, and the agreement between the tests was perfect. CONCLUSION: We can conclude that the Erns ELISA is a valid alternative that has several advantages compared to IPX. Our results clearly demonstrate that it performs well under Swedish conditions, and that its performance is comparable with the IPX test. It is highly sensitive and specific, can be used for testing of heat-inactivated samples, precolostral testing, and probably to detect PI animals at an earlier age than the IPX. PMID- 17352829 TI - Resolution of LPS-induced airway inflammation and goblet cell hyperplasia is independent of IL-18. AB - BACKGROUND: The resolution of inflammatory responses in the lung has not been described in detail and the role of specific cytokines influencing the resolution process is largely unknown. METHODS: The present study was designed to describe the resolution of inflammation from 3 h through 90 d following an acute injury by a single intratracheal instillation of F344/N rats with LPS. We documented the inflammatory cell types and cytokines found in the bronchoalveolar lavage fluid (BALF), and epithelial changes in the axial airway and investigated whether IL-18 may play a role in the resolution process by reducing its levels with anti-IL-18 antibodies. RESULTS: Three major stages of inflammation and resolution were observed in the BALF during the resolution. The first stage was characterized by PMNs that increased over 3 h to 1 d and decreased to background levels by d 6-8. The second stage of inflammation was characterized by macrophage influx reaching maximum numbers at d 6 and decreasing to background levels by d 40. A third stage of inflammation was observed for lymphocytes which were elevated over d 3-6. Interestingly, IL-18 and IL-9 levels in the BALF showed a cyclic pattern with peak levels at d 4, 8, and 16 while decreasing to background levels at d 1-2, 6, and 12. Depletion of IL-18 caused decreased PMN numbers at d 2, but no changes in inflammatory cell number or type at later time points. CONCLUSION: These data suggest that IL-18 plays a role in enhancing the LPS-induced neutrophilic inflammation of the lung, but does not affect the resolution of inflammation. PMID- 17352831 TI - Assessment of Survivor Concerns (ASC): a newly proposed brief questionnaire. AB - BACKGROUND: The purpose of this study was to design a brief questionnaire to measure fears about recurrence and health in cancer survivors. Research involving fear of recurrence has been increasing, indicating that it is an important concern among cancer survivors. METHODS: We developed and tested a six-item instrument, the Assessment of Survivor Concerns (ASC). Construct validity was examined in a multiple group confirmatory factor analysis (CFA) with 592 short term and 161 long-term cancer survivors. Convergent and discriminant validity was examined through comparisons with the PANAS (Positive and Negative Affect Schedule) and the CES-D (Center for Epidemiologic Studies Depression) measures. RESULTS: CFA models for the ASC with short- and long-term survivors showed good fit, with equivalent structure across both groups of cancer survivors. Convergent and discriminant validity was also supported through analyses of the PANAS and CES-D. One item (children's health worry) did not perform as well as the others, so the models were re-run with the item excluded, and the overall fit was improved. CONCLUSION: The ASC showed excellent internal consistency and validity. We recommend the revised five-item instrument as an appropriate measure for assessment of cancer survivor worries. PMID- 17352832 TI - Determining appropriateness for rehabilitation or other subacute care: is there a role for utilisation review? AB - BACKGROUND: Rehabilitation and other forms of subacute care play an important role in the Australian health care system, yet there is ambiguity around clinical definitions of subacute care, how it differs from acute care, where it is best done and what resources are required. This leads to inconsistent and often poorly defined patient selection criteria as well as a lack of research into efficient models of care. METHODS: A literature review on the potential role of utilisation review in defining levels of care and in facilitating appropriate care, with a focus on the interface between acute care and rehabilitation. RESULTS: In studies using standardised utilisation review tools there is consistent reporting of high levels of 'inappropriate' bed days in acute care settings. These inappropriate bed days include both inappropriate admissions to acute care and inappropriate continuing days of stay. While predominantly an instrument of payers in the United States, concurrent utilisation review programs have also been used outside of the US, where they help in the facilitation of appropriate care. Some utilisation review tools also have specific criteria for determining patient appropriateness for rehabilitation and other subacute care. CONCLUSION: The high levels of 'inappropriate' care demonstrated repeatedly in international studies using formal programs of utilisation review should not be ignored in Australia. Utilisation review tools, while predominantly developed in the US, may complement other Australian patient flow initiatives to improve efficiency while maintaining patient safety. They could also play a role in the identification of patients who may benefit from transfer from acute care to another type of care and thus be an adjunct to physician assessment. Testing of the available utilisation review tools in the Australian context is now required. PMID- 17352833 TI - Regulation of metabolic networks by small molecule metabolites. AB - BACKGROUND: The ability to regulate metabolism is a fundamental process in living systems. We present an analysis of one of the mechanisms by which metabolic regulation occurs: enzyme inhibition and activation by small molecules. We look at the network properties of this regulatory system and the relationship between the chemical properties of regulatory molecules. RESULTS: We find that many features of the regulatory network, such as the degree and clustering coefficient, closely match those of the underlying metabolic network. While these global features are conserved across several organisms, we do find local differences between regulation in E. coli and H. sapiens which reflect their different lifestyles. Chemical structure appears to play an important role in determining a compounds suitability for use in regulation. Chemical structure also often determines how groups of similar compounds can regulate sets of enzymes. These groups of compounds and the enzymes they regulate form modules that mirror the modules and pathways of the underlying metabolic network. We also show how knowledge of chemical structure and regulation could be used to predict regulatory interactions for drugs. CONCLUSION: The metabolic regulatory network shares many of the global properties of the metabolic network, but often varies at the level of individual compounds. Chemical structure is a key determinant in deciding how a compound is used in regulation and for defining modules within the regulatory system. PMID- 17352834 TI - Safety and efficacy of a generic fixed-dose combination of stavudine, lamivudine and nevirapine antiretroviral therapy between HIV-infected patients with baseline CD4 <50 versus CD4 > or = 50 cells/mm3. AB - BACKGROUND: Antiretroviral therapy (ART) with a generic fixed-dose combination (FDC) of stavudine (d4T)/lamivudine (3TC)/nevirapine (NVP) is widely used in developing countries. The clinical data of this FDC among very advanced HIV infected patients is limited. METHODS: A retrospective cohort study was conducted among ART-naive HIV-infected patients who were initiated a generic FDC of d4T/3TC/NVP between May 2004 and October 2005. Patients were categorized into 2 groups according to the baseline CD4 (group A: <50 cell/mm3 and group B: > or = 50 cell/mm3). RESULTS: There were 204 patients with a mean +/- SD age of 37.1 +/- 8.9 years, 120 (58.8%) in group A and 84 (41.2%) in group B. Median (IQR) CD4 cell count was 6 (16-29) cells/mm3 in group A and 139 (92-198) cells/mm3 in group B. Intention-to-treat analysis at 48 weeks, 71.7% (86/120) of group A and 75.0% (63/84) of group B achieved plasma HIV RNA <50 copies/ml (P = 0.633). On treatment analysis, 90.5% (87/96) in group A and 96.9% (63/65) in group B achieved plasma HIV RNA <50 copies/ml (P = 0.206). At 12, 24, 36 and 48 weeks of ART, mean CD4 were 98, 142, 176 and 201 cells/mm3 in group A and 247, 301, 336 and 367 cells/mm3 in group B, respectively. There were no differences of probabilities to achieve HIV RNA <50 copies/ml (P = 0.947) and CD4 increment at 48 weeks between the two groups (P = 0.870). Seven (9.6%) patients in group A and 4 (8.5%) patients in group B developed skin reactions grade II or III (P = 1.000). ALT at 12 weeks was not different from that at baseline in both groups (P > 0.05). CONCLUSION: Initiation of FDC of d4T/3TC/NVP in HIV-infected patients with CD4 <50 and > or = 50 cells/mm3 has no different outcomes in terms of safety and efficacy. FDC of d4T/3TC/NVP can be effectively used in advance HIV-infected patients with CD4 <50 cells/mm3. PMID- 17352835 TI - Risk of contamination of nasal sprays in otolaryngologic practice. AB - BACKGROUND: Reusable nasal-spray devices are frequently used in otolaryngologic examinations, and there is an increasing concern about the risk of cross contamination from these devices. The aim of our study was to determine, by means of microbiologic analysis, the safety of a positive-displacement or pump-type atomizer after multiple uses. METHODS: A reusable nasal spray bottle, pump, and tips were used in the nasal physical examination of 282 patients admitted to a tertiary otolaryngology clinic. The effectiveness of 2 different methods of prophylaxis against microbiologic contamination (the use of protective punched caps or rinsing the bottle tip with alcohol) was compared with that of a control procedure. RESULTS: Although there was no statistically significant difference in positive culture rates among the types of nasal spray bottles tested, methicillin resistant coagulase-negative staphylococci were isolated in 4 of 198 cultures. CONCLUSION: Given these findings, we concluded that additional precautions (such as the use of an autoclave between sprays, disposable tips, or disposable devices) are warranted to avoid interpatient cross-contamination from a reusable nasal spray device. PMID- 17352836 TI - Climatic factors associated with hospitalizations for rotavirus diarrhoea in children under 5 years of age. AB - This study compares the seasonality of rotavirus diarrhoeal hospital admissions and its relationship to climatic factors across three Australian cities. Weekly admission of rotavirus diarrhoea (1993-2003) in children aged <5 years and weekly average temperature and relative humidity for each city were modelled using a log linear model with a cubic trend and season. Interactions were included to test for differences in the effect of temperature and humidity between seasons and between cities. Admissions of rotavirus diarrhoea peaked in winter and spring and were lowest in summer. Higher temperature and humidity in the previous week were associated with a decrease in rotavirus diarrhoeal admissions in three cities. The effects of both temperature and humidity on rotavirus admissions in Brisbane differed across seasons. Strategies to combat outbreaks of rotavirus diarrhoea should take climatic factors and seasonal effects into consideration to plan for the excess seasonal hospital admissions. PMID- 17352837 TI - Protecting contacts of hepatitis A: what's the difference between vaccine and human normal immunoglobulin? AB - The efficacy of vaccine when time since exposure is prolonged (more than 1 week from onset of illness in the index case) is unknown, but is likely to be significantly lower than human normal immunoglobulin (HNIG). We estimated the number of additional secondary cases that may occur through giving vaccine instead of HNIG to contacts of cases of hepatitis A who are identified more than 1 week after onset in the index case. This was calculated for different levels of vaccine efficacy, assuming HNIG efficacy to be 80-90%. The number of households that need to be treated to prevent one secondary case was calculated using estimates of secondary attack ratios (AR). If more than 1 week has elapsed from onset of illness in the index case, for an average household size of 2.3 people, a vaccine efficacy of 50% and an AR of 10-25%, 8-26 households would need to be treated with vaccine before one additional secondary case would be observed. As UK public health professionals manage around one hepatitis A case per month, it would take from 8 months to over 2 years for them to observe one additional case amongst contacts using vaccine rather than HNIG. It is unlikely that an average practitioner would notice if vaccine were 30% less effective than HNIG. Public health practice and advice to patients and contacts should be based on evidence as well as experience. PMID- 17352838 TI - Ten years of viral and non-bacterial serology in adults with cystic fibrosis. AB - Viral infections are associated with pulmonary exacerbations in children with cystic fibrosis (CF), but few studies have addressed the frequency in adults. This paper investigates the frequency and impact of viral infections in adults with CF receiving intravenous antibiotics. Pre- and post-treatment spirometry, inflammatory markers and antibody titres against influenza A, influenza B, adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae, Chlamydia psittaci, and Coxiella burnetti were analysed over a 10-year period. Non bacterial infections were identified in 5.1% of 3156 courses of treatment. The annual incidence of admissions per patient associated with viral infection was 4.9%. The presence of viral infection in association with a pulmonary exacerbation did not adversely affect lung function or inflammatory markers in the short term. Adults with CF have a lower incidence of respiratory viral infections associated with pulmonary exacerbations requiring intravenous antibiotics compared to children and infants with CF. PMID- 17352839 TI - Evaluating measles surveillance using laboratory-discarded notifications of measles-like illness during elimination. AB - For jurisdictions implementing measles elimination strategies, a minimum surveillance benchmark of 1/100 000 population per year measles-like illness (MLI) cases initially notified, but then rejected based on laboratory testing was proposed. We used this standard to assess the quality of the Victorian enhanced measles surveillance between 1998 and 2003. Victorian enhanced measles surveillance includes interviews with notified cases and confirmatory laboratory testing for notifications. We found 72% (918/1281) of measles notifications were discarded after testing. The median annual rate of discard was 2.9/100 000. The annual discard rate was inversely associated with the age of the notifications, and measles negative with no other diagnosis made was the most common laboratory outcome. The annual rates of discarded notifications in Victoria were consistently above the minimum recommended standard. The rate of discarded MLIs as a surveillance threshold should be useful in measles endemic regions, but may require modification where disease elimination has occurred. PMID- 17352840 TI - Estimating infectious diseases incidence: validity of capture-recapture analysis and truncated models for incomplete count data. AB - Capture-recapture analysis has been used to evaluate infectious disease surveillance. Violation of the underlying assumptions can jeopardize the validity of the capture-recapture estimates and a tool is needed for cross-validation. We re-examined 19 datasets of log-linear model capture-recapture studies on infectious disease incidence using three truncated models for incomplete count data as alternative population estimators. The truncated models yield comparable estimates to independent log-linear capture-recapture models and to parsimonious log-linear models when the number of patients is limited, or the ratio between patients registered once and twice is between 0.5 and 1.5. Compared to saturated log-linear models the truncated models produce considerably lower and often more plausible estimates. We conclude that for estimating infectious disease incidence independent and parsimonious three-source log-linear capture-recapture models are preferable but truncated models can be used as a heuristic tool to identify possible failure in log-linear models, especially when saturated log-linear models are selected. PMID- 17352841 TI - Epidemic influenza and vitamin D. PMID- 17352842 TI - Re: epidemic influenza and vitamin D. PMID- 17352843 TI - Epigenetic control of cellular senescence in disease: opportunities for therapeutic intervention. AB - Understanding how senescence is established and maintained is an important area of study both for normal cell physiology and in tumourigenesis. Modifications to N-terminal tails of histone proteins, which can lead to chromatin remodelling, appear to be key to the regulation of the senescence phenotype. Epigenetic mechanisms such as modification of histone proteins have been shown to be sufficient to regulate gene expression levels and specific gene promoters can become epigenetically altered at senescence. This suggests that epigenetic mechanisms are important in senescence and further suggests epigenetic deregulation could play an important role in the bypass of senescence and the acquisition of a tumourigenic phenotype. Tumour suppressor proteins and cellular senescence are intimately linked and such proteins are now known to regulate gene expression through chromatin remodelling, again suggesting a link between chromatin modification and cellular senescence. Telomere dynamics and the expression of the telomerase genes are also both implicitly linked to senescence and tumourigenesis, and epigenetic deregulation of the telomerase gene promoters has been identified as a possible mechanism for the activation of telomere maintenance mechanisms in cancer. Recent studies have also suggested that epigenetic deregulation in stem cells could play an important role in carcinogenesis, and new models have been suggested for the attainment of tumourigenesis and bypass of senescence. Overall, proper regulation of the chromatin environment is suggested to have an important role in the senescence pathway, such that its deregulation could lead to tumourigenesis. PMID- 17352844 TI - Efficacy of Gyrus diego microdissector at varying oscillation speeds. AB - OBJECTIVE: To determine the efficacy of the Gyrus diego microdissector at increasing oscillation speeds, using an in vitro tissue model. BACKGROUND: It had not previously been established whether microdissectors were more efficient at higher or lower speeds. METHODS: We investigated the effect of varying microdissector oscillation speeds on the weight of material aspirated in a given time. A 4 mm straight blade was used with constant suction strength. Jelly and liver were used to simulate polyps and muscle plus connective tissue, respectively. Water was used as a control. Repeat readings were taken at speeds of 1000, 2000, 3000, 4000 and 5000 rpm. Data were analysed using linear bivariate regression. RESULTS: The results showed significant linear trends in the cases of liver and jelly, with faster cutter speeds being associated with higher aspiration rates. CONCLUSION: These results suggest that microdissector efficacy increases with speed, up to 5000 rpm. PMID- 17352845 TI - Seroprevalence of Helicobacter pylori infection in patients with chronic nonspecific pharyngitis: preliminary study. AB - BACKGROUND AND OBJECTIVES: Chronic nonspecific pharyngitis is a chronic inflammation of the pharynx. It is found worldwide, and treatment is difficult. The underlying aetiopathogenesis is still controversial. The aim of this study was to investigate Helicobacter pylori seroprevalence in chronic nonspecific pharyngitis patients without other possible causative factors for chronic pharyngeal irritation and without H. pylori gastric mucosal infection. MATERIALS AND METHODS: Forty-one patients with symptoms of chronic nonspecific pharyngitis and 30 healthy control subjects were enrolled in this prospective, controlled, clinical study. In both study and control groups, selected patients were shown to have gastric mucosa uninfected by H. pylori, as demonstrated by the 14C-urea breath test. Comprehensive otorhinolaryngological examination did not elicit any factor contributing to the chronic pharyngeal complaint. Serum H. pylori immunoglobulin G antibody titres were assayed using serum enzyme-linked immunosorbent assay. The difference between the study and control groups was analysed by the chi-square test (the likelihood ratio was used). RESULTS: Thirty two of the 41 patients (78 per cent) and 14 of the 30 control subjects (46.7 per cent) were found to be H. pylori positive. Patients with chronic nonspecific pharyngitis were found to have a significantly higher rate of H. pylori seropositivity than the control group (p = 0.016). CONCLUSION: These data may be important in developing future treatment strategies for chronic nonspecific pharyngitis. PMID- 17352846 TI - Otitis media with effusion: what parents want to know. AB - INTRODUCTION: Otitis media with effusion is a common condition of childhood. The development of an information leaflet for parents of children with the condition, and its impact on clinical management, have not previously been examined. PATIENTS AND METHODS: Eighteen doctors and 38 parents assessed the content of an information leaflet on otitis media with effusion, by applying two rounds of the modified Delphi technique. A qualitative assessment of content items was also performed. RESULTS: From the 23-item list used in the first assessment round, four items had a low doctor-parent agreement and seven were excluded. Differences were also noticed in comments on the value of such leaflets, with parents being more positive about the value of leaflet distribution. CONCLUSION: During the consultation, doctors may not tell parents what they want to know, especially regarding daily care of their child. An information leaflet, developed using the Delphi technique, can help reduce this discrepancy and increase parents' satisfaction. PMID- 17352847 TI - A pilot effectiveness study: placebo-controlled trial of adjunctive L triiodothyronine (T3) used to accelerate and potentiate the antidepressant response. AB - The aim was to evaluate whether adjunctive T3 can help accelerate the antidepressant response and improve overall outcomes when used under naturalistic conditions. Fifty consecutive psychiatric outpatients diagnosed with major depressive disorder who were initiated on antidepressant therapy were randomized to receive adjunctive T3 or placebo in a double-blind manner over the course of 6 wk. There were no restrictions placed on the selection of antidepressant agent, dosing, ancillary medications, or psychotherapy, and there were few exclusion criteria. A positive response was defined as a > or = 50% reduction in Montgomery Asberg Depression Rating Scale scores. Response rates were higher for the adjunctive T3 cohort compared to the adjunctive placebo cohort after 1 wk (45% vs. 24%) and 2 wk (57% vs. 33%) of treatment. The likelihood of experiencing a positive response at any point over the 6-wk trial was 4.5 times greater in the adjunctive T3 cohort (95% CI 1.3-15.7). The study provides preliminary evidence that T3 can successfully be used in clinical practice to accelerate the antidepressant response and improve overall outcomes. The effectiveness model may be an untapped mechanism for evaluating the value of psychopharmacological agents. PMID- 17352848 TI - Effect of Plasmodium yoelii nigeriensis infection on hepatic and splenic glutathione-S-transferase(s) in Swiss albino and db/+ mice: efficacy of mefloquine and menadione in antimalarial chemotherapy. AB - The present report deals with the status of hepatic and splenic glutathione-S transferase (GST) activities in mice during experimental infection with Plasmodium yoelii nigeriensis and subsequent treatment of infected mice with mefloquine (Mf) and menadione (Md). The infection caused significant decline in the hepatic and splenic glutathione-S-transferase (GST) activities of albino and db/+ mice. The decline was observed in the levels of both cytosolic and microsomal GST(s) of liver and spleen in both types of mice. Intraperitoneal administration of mefloquine at a dose of 5 mg/kg and menadione at a dose of 100 mg/kg, twice daily from day 1 p.i. (day 0) until day 10, caused restoration in the levels of hepatic as well as splenic GST(s), albeit to varying degrees. Mf was able to suppress parasitaemia by day 5 in the case of albino mice and by day 3 in the case of db/+ mice but was unable to cure both types of mice completely. On the other hand, Md caused a delay in maturation of infection in both cases, but could not cure the mice. PMID- 17352849 TI - Genetic characterization of members of the genus Contracaecum (Nematoda: Anisakidae) from fish-eating birds from west-central Florida, USA, with evidence of new species. AB - Specimens of Contracaecum spp. from Phalacrocorax auritus and Pelecanus occidentalis from Florida were characterized by sequencing of the small subunit of the mitochondrial ribosomal RNA gene (rrnS) and by PCR-based RFLP analysis of the same gene and of the internal transcribed spacers (ITS) of nuclear ribosomal DNA. Analyses of the rrnS sequence data using the MP and UPGMA approaches yielded trees with similar topologies, delineating 3 main clusters. Specimens from Ph. auritus, morphologically assigned to C. rudolphii (s.l.), were part of the cluster comprising also the other 2 species of the C. rudolphii complex (A and B), but representing a genetically distinct group, potentially corresponding to a distinct lineage within the complex, provisionally named as C. rudolphii C. The second cluster comprised 5 individuals from P. occidentalis, which formed a genetically relatively homogeneous group. The rrnS data indicate that these specimens (indicated as Contracaecum sp. 1) are clearly genetically different from the morphologically most closely related species, i.e. C. rudolphii (s.l.) and C. microcephalum, and could represent a new species. The third cluster comprised 7 specimens from P. occidentalis morphologically assigned to C. multipapillatum (s.l.). These were shown to be genetically homogeneous and related to but quite distinct from C. multipapillatum from Greece, although additional studies are needed to assess their status. PCR-RFLP based markers for the quick identification of these taxa are provided. PMID- 17352851 TI - [Introduction: cardiology: 2006]. PMID- 17352850 TI - Theileria parva live vaccination: parasite transmission, persistence and heterologous challenge in the field. AB - The 'Muguga cocktail' live vaccine, delivered by an infection and treatment protocol, has been widely deployed in Eastern, Central and Southern Africa to protect cattle against East Coast fever, caused by Theileria parva. The vaccine contains 3 component stocks (Muguga, Serengeti-transformed and Kiambu 5). In a previous study, parasites from vaccinated and unvaccinated animals were genotyped with a panel of micro- and minisatellite markers (Oura et al. 2004a) and it was shown that only the Kiambu 5 stock establishes a long-term carrier state but there was no evidence for the transmission of this stock. Also parasite genotypes different from the 3 component vaccine stocks were identified in vaccinated animals. We now report a follow-up study on the same farm, some 4 years after the initial vaccination, aimed at establishing the source of the novel parasite genotypes identified in vaccinated cattle, determining the longevity of the carrier state established by the Kiambu 5 vaccine stock and re-examining whether vaccine transmission can occur over a longer time-scale. To do this, samples were taken from vaccinated and unvaccinated cattle and the parasites were genotyped with a series of micro- and minisatellite markers. The data indicate that the vaccine stabilates contain at least 6 parasite genotypes, the Kiambu 5 stock can be detected in many but not all vaccinated cattle for up to 4 years and can be transmitted to unvaccinated cattle which share grazing and that some of the vaccinated animals become infected with local genotypes without causing overt disease. PMID- 17352852 TI - [Ischemic heart disease: 2006 update]. AB - This article contains a review of the main developments reported in publications and conference presentations in 2006 on the pathophysiology, secondary prevention, prognosis, and treatment of ST-segment elevation and non-ST-segment elevation acute coronary syndrome. The latest clinical practice guidelines are also discussed. PMID- 17352853 TI - [Interventional cardiology 2006]. AB - The range of applications of percutaneous coronary intervention (PCI) continues to expand and a growing number of patients are being treated, including those with extensive cardiovascular disease, more serious comorbid conditions, and more complex lesions. Even so, the success rate is high, serious complications are rare in stable patients, and the restenosis rate has been dramatically reduced by drug-eluting stents. Nevertheless, percutaneous techniques still have major limitations restricting their use in some type of lesions, such as bifurcations and total occlusions, and their role in relation to surgical revascularization has not yet been well defined in the treatment of the left main coronary artery or multivessel disease. The development of novel types of coated stent with better mechanical characteristics and a lower risk of occlusion will further expand the ambit of PCI. The role of PCI in the management of acute coronary syndromes is already well defined, and has increased the preference for an invasive rather than a conservative approach in high-risk patients without ST elevation and the preference for primary angioplasty rather than thrombolysis in those with ST elevation. The development and implementation of integrated coronary syndrome treatment networks will enable human and material resources to be used efficiently, and will guarantee rapid access to high-quality PCI for those who need it. The potential usefulness of combining cellular therapy with interventional procedures in the treatment of acute myocardial infarction has still to be determined. At present, there is extensive research into noncoronary interventions, which, in the not too distant future, could provide percutaneous treatment for the many elderly patients with severe aortic stenosis who are not currently eligible for surgery. PMID- 17352854 TI - [Arrhythmias and cardiac electrophysiology]. AB - In the past few months, numerous articles have been published on arrhythmias and cardiac electrophysiology. As in previous years, a substantial proportion of researchers have concentrated on atrial fibrillation, both on catheter ablation of chronic and paroxysmal atrial fibrillation and on the development of new approaches to thromboembolism prophylaxis. The feasibility of atrial fibrillation ablation by remote control has been demonstrated and a step-wise approach to ablation has been proposed, which appears to improve outcome and reduce lesion size. In addition, multicenter randomized trials have shown that the improvements in functional class and left ventricular ejection fraction achieved by ablation in patients with chronic atrial fibrillation are greater than those resulting from pharmacological treatment. New strategies are being developed to improve the selection of patients for defibrillator implantation and to decrease the number of high-energy discharges occurring during follow-up. Controlled trials continue to demonstrate that pharmacological therapy is of little value in preventing recurrence of vasovagal syncope compared with maneuvers involving isometric muscular contraction. Finally, one of the most significant events in the last year was the publication of new clinical practice guidelines by European and American societies of cardiology. These provide important recommendations on the treatment and prevention of ventricular arrhythmias and sudden death and on the management of and thromboembolic prophylaxis in atrial fibrillation. PMID- 17352855 TI - [Update on cardiac imaging techniques. Echocardiography, cardiac magnetic resonance imaging, and multidetector computed tomography]. AB - This article contains a review of the most significant publications on non invasive recent cardiac imaging techniques in 2005. The increasing importance of technological innovation in echocardiography is reflected in the sections on three dimensional echocardiography, contrast echocardiography, and myocardial deformation measurement techniques (i.e., strain echocardiography). The most important developments affecting cardiology in the techniques of magnetic resonance imaging and multidetector computed tomography are also summarized. This review ends with a detailed description of the contributions made by imaging techniques to the diagnosis of aortic disease. PMID- 17352856 TI - [Heart failure in 2006]. AB - This article are summarizes the most relevant articles in the field of heart failure including epidemiology, diagnostic and therapeutic issues. Therapy includes drugs, cardiac resinchronization therapy, automatic implantable defibrillator, heart transplantation and cell therapy. Stem cell therapy is feasible and short term data indicates it is safe. However there are unresolved concerns on arrhythmias, restenosis and efficacy. At this point experts recommend that medium-sized randomized controlled trials, using surrogate endpoints, should be carried out to establish the efficacy and safety of this form of treatment. PMID- 17352857 TI - [Cardiovascular disease prevention and cardiac rehabilitation]. AB - This article reviews the main developments in cardiovascular disease prevention reported in recent publications. The prevention of coronary heart disease often begins with the identification of risk factors. Better understanding of emerging risk factors could help to improve risk assessment and increase the efficacy of preventative measures. Lifestyle modification and the introduction of better tolerated and effective new drugs have been shown to prevent atherosclerosis and prolong survival. PMID- 17352858 TI - [Global treatment of cardiovascular risk in the hypertensive patient]. AB - During 2006, new evidence supporting the need to adopt a global approach to the treatment of cardiovascular risk in hypertensive patients has been reported. It is increasingly clear that it is not sufficient to aim for optimum blood pressure control, which in any case is not easy to achieve, and that it is essential to treat all cardiovascular risk factors by using drugs with proven benefits, even when those benefits are supplementary to the drug's principal effects. In addition, drugs that could have a detrimental effect or that are, merely, less beneficial should be avoided or kept as a last resort. This appears to have happened with atenolol, and with beta-blockers in general, which have been withdrawn as first-line treatment in the recommendations of some professional societies. To lower cardiovascular risk, it is essential to prevent the development of conditions like diabetes, which are known to have drastic effect on the patient's prognosis. Recently, the results of the DREAM study, which are discussed in detail in this article, have been reported. They could lead to a change in therapeutic strategy in patients who are expected to develop diabetes. In addition, this year has seen the publication of substantial data on a new antihypertensive agent, aliskiren, the first oral renin inhibitor. It is awaiting approval by the international medicine agencies (i.e., the FDA and the EMEA), but should provide a very promising tool in the difficult area of high blood pressure management. Despite numerous advances in the pharmacologic treatment of high blood pressure, control is very difficult to achieve, principally in the elderly, in whom the prevalence of hypertension is high. In these patients, social factors and difficulties with treatment compliance also have an influence and must be dealt with by public health measures aimed at improving blood pressure control. PMID- 17352859 TI - [Progress in cardiac pacing 2006]. AB - This article summarizes progress in cardiac pacing that has taken place in the last year, such as the incorporation of navigation technology into programmers, systems for monitoring hemodynamic parameters, and new developments in patient follow-up, principally home monitoring and the use of treatment guidelines. In addition, the article covers recent findings in resynchronization therapy, paroxysmal atrial fibrillation, and the management of patients with pacemakers who need to undergo magnetic resonance imaging. PMID- 17352860 TI - [Recent developments in metabolic syndrome, population aging, and the clinical interpretation of new atrial fibrillation guidelines]. AB - This article reviews the main developments reported during the last year concerning metabolic syndrome, population aging, and new atrial fibrillation guidelines. The principal aim was to provide the clinical cardiologist with an overview of recent 2006 publications and conference reports on these topics, which have been selected for their broad clinical implications. PMID- 17352861 TI - [Foundation and application of aggregation syndrome theory in traditional Chinese medicine]. AB - This paper proposes a new idea of the theory of Ju (aggregation) syndrome complex based on succeeding to traditional Chinese medicine. It presumes that the etiological factors of Ju are both heritage deficiency and postnatal viscerae damage, which cause the disturbance of qi-transformation, and thus, the evil heat, turbid damp and stagnated blood take the chance of retention in the body, to block up the production and distribution of the essence and energy. Ju is a mixed symptom complex of asthenia and sthenia, and should be simultaneously applied to purging-tonifying therapy and aggregation-dissipating method. Under the guidance of Ju theory, patients with metabolic syndrome were treated with Chinese medicine. The symptoms were relieved, and the insulin resistance, hyperglycemia, hyperlipidemia, body weight, waist circumference, and the inflammatory cytokines were improved, which confirmed the theoretical significance of the practical value of Ju theory. PMID- 17352862 TI - [Study of standardization of syndrome diagnosis: an analysis of current status]. AB - It is one of the key problems for the development of Chinese medicine to standardize the diagnosis of syndromes. The authors mainly discuss the ideas and methods of the study of standardization of syndrome diagnosis by retrospective analysis, also put forward the following suggestions: (1) the main ideas of this study should be based on the comparison of the diseases and their relevant syndromes and the predictive diagnosis of syndromes by the effects of herbal prescription treatment; (2) they are important ways to carry out multicenter, large sample and perspective clinical trials on the basis of the investigation and study of literature, consultation of experts and retrospective case review, and following the principles of clinical epidemiology, and to use the methods of evidence-based medicine to do systemic evaluation on the criteria of syndrome diagnosis; (3) they are important sectors of the study of standardization of syndrome diagnosis to enhance the objective studies on the four diagnostic methods of traditional Chinese medicine, and to do the functional studies under the conduction of systems biology; (4) Both data excavation technology and computer intelligence are the important technique supporting this study. PMID- 17352863 TI - [Breast cancer pathogenesis of stagnation of phlegm, poison and blood stasis: rationale and clinical application in traditional Chinese medicine]. AB - Breast cancer is called "Ruyan" in literature of traditional Chinese medicine. We synthesized the ancient and contemporary discussions and raised the theory that "Duxie" (poisonous pathogenic factor) is the etiological factor and pathologic product through the whole course of breast cancer. "Liuyin Fudu" (latent poison of six exogenous pathogenic factors) and "Qiqing Yudu" (stagnant poison of seven emotions) are the main etiological factors affecting the breast cancer occurrence. "Aidu Neisheng" (internal product of cancer poison) is the essential change in breast cancer occurrence. "Tandu Yujie" (stagnation of phlegm, poison and blood stasis) is the essential pathogenesis of the breast cancer's development. "Yudu Weiqing" (vestigial poison) is the main pathogenesis of breast cancer after operation. "Yudu Pangcuan" (vestigial poison invasion elsewhere) is the key pathogenesis of recurrence and metastasis after operation. "Sanjie Jiedu" (dispersing accumulation and detoxification) is an important therapeutic principle in breast cancer's treatment after operation. The "Tandu Yujie" pathogenesis theory and "Sanjie Jiedu" therapeutic principle developed the theory about breast cancer in traditional Chinese medicine, and have some clinical application value. PMID- 17352864 TI - [Correlation between syndrome differentiation and CT quantitative diagnosis of fatty liver]. AB - OBJECTIVE: To explore the correlation between syndrome differentiation and CT quantitative diagnosis of fatty liver. METHODS: One hundred and thirteen cases of fatty liver verified clinically accepted plain CT scan after syndrome differentiation (syndrome of stagnation of liver qi and spleen deficiency, syndrome of intermingled phlegm and blood stasis, syndrome of phlegm-dampness blocking internally, syndrome of deficiency of liver and kidney, syndrome of interior dampness-heat), and then the CT values of the liver and the spleen were measured respectively. RESULTS: It was shown that there was a correlation between the syndrome differentiation and the fatty infiltration in the liver. Significant differences of the distribution of fat and the ratio of liver-spleen were found among the five different syndromes (P<0.05). Diffused, mild fatty liver mainly displayed syndrome of stagnation of liver qi and spleen deficiency. CONCLUSION: Syndrome differentiation of fatty liver is correlated with CT quantitative diagnosis, which can be discriminated by the ratio of liver-spleen. PMID- 17352865 TI - [Correlation between syndromes of posthepatitic cirrhosis and biological parameters: a report of 355 cases]. AB - OBJECTIVE: To investigate the pathological factors of syndrome pathomechanism through studying the correlation between syndromes of posthepatitic cirrhosis and biological parameters. METHODS: Clinical information of three hundred and fifty five patients with posthepatitic cirrhosis was collected and the database was established. Parameters with statistical significance were analyzed with multi factor regression analysis to investigate the main influencing factors of the syndromes of posthepatitic cirrhosis. RESULTS: Formulae of six syndromes, including syndrome of yin deficiency of liver and kidney, syndrome of damp heat, syndrome of stagnated heat smoldering, syndrome of yang deficiency of spleen and kidney, syndrome of stagnation of liver qi and spleen deficiency and syndrome of blood stasis due to qi deficiency, were established with stepwise regression analysis. CONCLUSIONS: One of the pathophysiological bases of syndrome of blood stasis due to qi deficiency in cirrhosis is synthetic dysfunction of hepatocytes. The pathophysiological basis of syndrome of damp heat is inflammatory injury, which is also syndrome of stagnated heat smoldering in cirrhosis patients. The relationship between syndrome of yin deficiency of liver and kidney and stasis and damp heat may be the pathophysiological basis of the posthepatitic cirrhosis.. PMID- 17352866 TI - [Clinical early intervention of Tongxia Huayu Decoction on pancreatic microcirculatory disturbance in severe acute pancreatitis]. AB - OBJECTIVE: To study the mechanisms of Tongxia Huayu Decoction (a Chinese herbal decoction for purgation and removing blood stasis) in prognostic improvement for severe acute pancreatitis by early intervention on pancreatic microcirculatory disturbance. METHODS: Fifty-three patients with severe acute pancreatitis were divided randomly into treatment group (n=28) and control group (n=25). Tongxia Huayu Decoction was given to the patients in treatment group in addition to the normal treatment in control group for one week. The clinical symptoms and signs, hemodiastase, urinary amylase, C-reactive protein (CRP) and endothelin (ET) of the patients in the two groups before and after treatment were observed and detected. RESULTS: The total response rate of the treatment group was 98.4%, while that of the control group was 80%, with significant difference between them (P<0.05). There was no significant difference of the contents of hemodiastase, urinary amylase, CRP and ET between the two groups before treatment, while they were significantly decreased after treatment (P<0.01) with more obvious change in treatment group (P<0.01). CONCLUSION: Tongxia Huayu Decoction brings satisfied therapeutic effect on severe acute pancreatitis. The mechanisms may associate with its reducing function on ET releasing so as to inhibit the pancreatic microcirculatory disturbance and acinar cell injury induced by ET. PMID- 17352867 TI - [Treatment of beta-thalassemia with Bushen Yisui therapy: a randomized controlled trial]. AB - OBJECTIVE: To investigate the efficacy and safety of Yisui Shengxue Granule (YSSXG), a compound traditional Chinese herbal medicine, in treating beta thalassemia. METHODS: A randomized single-blinded trial was designed. Sixty patients with beta-thalassemia were divided into two groups: 30 patients in YSSXG treated group and 30 in placebo parallel-control group. The patients in the two groups were assigned to receive either YSSXG or placebo for three months. The patients' symptoms and their blood indexes such as hemoglobin (Hb), red blood cell (RBC), reticulocytes (Ret) and fetal hemoglobin (HBF) were examined before and after the treatment. Meanwhile, the liver and spleen were examined with B mode ultrasound. RESULTS: In the YSSXG-treated group, the blood indexes (Hb, RBC, Ret and HBF) and the symptoms of the patients were improved after three-month treatment, with statistical significance compared to those before treatment (P<0.01); hepatauxe and splenomegaly were also relieved (P<0.05) and no adverse reactions were monitored. In the placebo parallel-control group, no significant improvement of the blood indexes and symptoms, as well as the hepatauxe and splenomegaly had been found (P>0.05). CONCLUSION: YSSXG demonstrates obvious clinical efficacy and no adverse reactions in treating beta-thalassemia. PMID- 17352868 TI - [A double-blind, randomized controlled trial of Chaige Qingre Granule in treating acute upper respiratory tract infection of wind heat syndrome]. AB - OBJECTIVE: To evaluate the safety and efficacy of Chaige Qingre Granule, a traditional Chinese compound herbal medicine, in treating acute upper respiratory tract infection of wind heat syndrome. METHODS: A multi-center, double-blinded, randomized controlled trial was conducted. In the phase II, 60 patients with acute upper respiratory tract infection were randomly divided into the trial group (n=30) and the control group (n=30). In the phase III, 112 patients were randomly divided into the trial group (n=84) and the control group (n=28). The trial group received 6 g Chaige Qingre Granule, and the control group received 6 g Fufang Shuanghua Granule (another traditional Chinese compound herbal medicine). The two groups were all treated for 3 days and four times daily. Clinical symptoms, syndromes, adverse effect, blood, urine and stool test, hepatorenal function and electrocardiogram were examined before and after the treatment. RESULTS: After treatment, the overall obvious response rates of the trial group and the control group were 78.57%, 82.14% (by per-protocol analysis) and 75.86%, 79.31% (by intention-to-treat analysis) respectively, and the overall response rates of the two groups were 96.43%, 100% (by per-protocol analysis) and 93.10%, 96.55% (by intention-to-treat analysis) respectively in phase II. There were no significant differences between the two groups (P>0.05). In the phase III, the overall obvious response rates of the trial group and the control group were 90.54%, 73.08% (by per-protocol analysis) and 88.16%, 70.37% (by intention to-treat analysis) respectively, and the overall response rates of the two groups were 94.59%, 96.15% (by per-protocol analysis) and 92.11%, 92.59% (by intention to-treat analysis) respectively. There were no statistical differences between the two groups (P>0.05) too. No adverse effects were found in the trial. CONCLUSION: Chaige Qingre Granule is effective and safe in treating acute upper respiratory tract infection of wind heat syndrome. PMID- 17352869 TI - [Clinical observation of Ruyiping in preventing recidivation and metastasis of breast cancer]. AB - OBJECTIVE: To observe the effect of Ruyiping, a traditional Chinese compound herbal medicine composed of 5 Chinese herbs for removing toxic materials and dissipating nodules from Runing II, another traditional Chinese compound herbal medicine for treating breast cancer, in preventing recidivation and metastasis in breast cancer patients after operation. METHODS: Eighty patients with breast cancer after operation were randomly divided into Ruyiping group and Runing II group, and prescribed Ruyiping and Runing II on the basis of chemotherapy, radiotherapy and endocrine therapy respectively for two years. RESULTS: There were two patients with metastasis and three patients lost to follow-up in Ruyiping group and three and two in Runing II group. The recidivation and metastasis rates were 5.41% and 7.89% respectively. The difference between the two groups was not statistically significant (P>0.05). The difference of disease free survival time between the two groups was also not statistically significant. CONCLUSIONS: The effect of Ruyiping in preventing recidivation and metastasis is similar to that of Runing II. Ruyiping is the essential component of Runing II for preventing recidivation and metastasis. The result provides some clinical evidences for the theory that "Yudu Pangcuan" (vestigial poison invasion elsewhere) is the essential pathogenesis of breast cancer's recidivation and metastasis and the utilization of "Sanjie Jiedu" (dispersing accumulation and detoxification) is the therapeutic principle in preventing recidivation and metastasis after operation. PMID- 17352870 TI - [Establishment and analysis of serum two-dimensional gel electrophoresis profiles of myasthenia gravis patients with spleen and kidney deficiency syndrome]. AB - OBJECTIVE: The purpose of this study was to establish two-dimensional gel electrophoresis (2-DE) profiles of serum of myasthenia gravis patients, and to identify the differential proteomic expressions between normal persons and myasthenia gravis patients with spleen and kidney deficiency syndrome. METHODS: Samples of serum protein were extracted by repeated freeze-thaw method and separated by two-dimensional electrophoresis. Differential proteomic expressions between the myasthenia gravis patients and the normal control persons were identified by two-dimensional polyacrylamide gel electrophoresis, silver staining, image-master 2-DE software analysis, peptide mass fingerprinting based on matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), BioWorks and NCBI software database searching. RESULTS: The two dimensional polyacrylamide gel electrophoresis profiles of serum proteins were successfully established by 2-DE. Twenty-one of the significant differential proteins were selected and identified by MALDI-TOF-MS. Eight of them were finally identified. CONCLUSIONS: The 2-DE profiles of serum proteins were established and the differential proteomic expressions were identified by proteome technique in our study. This can be an experimental basis for further research of the pathogenesis and treatment of myasthenia gravis. PMID- 17352871 TI - [Inhibition action of bufalin on human transplanted hepatocellular tumor and its effects on expressions of Bcl-2 and Bax proteins in nude mice]. AB - OBJECTIVE: To investigate the anti-tumor effect of bufalin and its regulation on Bcl-2 and Bax proteins in orthotopically transplanted tumor of human hepatocellular carcinoma in nude mice. METHODS: Orthotopically transplanted tumor of human hepatocellular carcinoma was established in nude mice. The mice were randomly divided into five groups: high-dose bufalin-treated group (1.5 mg/kg), medium-dose bufalin-treated group (1 mg/kg), low-dose bufalin-treated group (0.5 mg/kg), adriamycin-treated group (8.0 mg/kg), and normal saline-treated group. After 25 days, mice were sacrificed. The tumor volume was measured, and the pathological changes of tumor tissues were detected by HE staining to observe the tumor necrosis degree. Cell morphological changes were also observed by an electron microscopy. Label index of tumor cell apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and the expressions of Bcl-2 and Bax proteins were determined by immunohistochemical method. RESULTS: The tumor volume in the bufalin-treated groups was shrunk significantly compared with that in the normal saline-treated group (P<0.01). The survival time of the bufalin-treated groups was prolonged compared with that of the adriamycin-treated group and the normal saline-treated group P<0.05. Apoptotic characteristics could be seen in tumor tissues of the bufalin-treated groups. The label index of tumor cell apoptosis in the bufalin-treated groups (5.87+/-2.13, 8.86+/-2.96 and 10.60+/-3.42 in low-, medium- and high-dose groups respectively) was higher than that in the adriamycin-treated group (3.28+/-0.98) (P<0.05, P<0.01). The expression of Bax was up-regulated, while no changes were detected as to Bcl-2 protein in tumors of the bufalin-treated groups. CONCLUSION: Bufalin has significant anti-tumor effect on the orthotopically transplanted tumor of human hepatocellular carcinoma in nude mice. Its effect might be related to up-regulation of Bax protein and inducement of the tumor cell apoptosis. PMID- 17352872 TI - [Effects of Yiqi Kaimi Recipe on gastrointestinal motility and neuropeptides in rats with colonic slow transit constipation]. AB - OBJECTIVE: To observe the effects of Yiqi Kaimi Recipe (YQKMR), a traditional Chinese compound medicine, on gastrointestinal motility and neuropeptides in rats with colonic slow transit constipation. METHODS: Eighty specific pathogen free rats were included, and there were sixty rats with slow transit constipation (STC) and twenty normal rats. Sixty rats with STC were randomly divided into untreated group, cisapride-treated group and YQKMR-treated group, and twenty normal rats were allocated to normal control group. Percentage of carbon propelling, contraction frequency and amplitude of the muscle segments in vitro, and expressions of nitric oxide synthase-1 (NOS1) and substance P proteins were observed. RESULTS: Compared with the normal control group, the percentage of carbon propelling, and the contraction frequency and amplitude of the muscle segments in the untreated group decreased obviously (P<0.05) The percentage of carbon propelling, and the contraction frequency and amplitude of the muscle segments in the YQKMR-treated group and cisapride-treated group were higher than those in the untreated group (P<0.05). The expression of NOS1 protein in the untreated group was higher than that in the normal control group, YQKMR-treated group and cisapride-treated group. However, there were no significant differences between the YQKMR-treated group and the normal control group (P>0.05). The expression of substance P protein in the untreated group was lower than that in the normal control group, and there was no significant difference between the YQKMR-treated group and the normal control group too (P>0.05). CONCLUSION: Yiqi Kaimi Recipe could promote colon motility by increasing the contraction frequency and amplitude of the smooth muscle, and this may be due to its effect of regulating the expressions of NOS1 and substance P proteins in the enteric plexus. PMID- 17352873 TI - [Effects of Chinese herbs for replenishing qi and resolving stagnation on hypoxia inducible factor-1alpha and vascular endothelial growth factor in granulation tissue of skin ulcers in rats with diabetes]. AB - OBJECTIVE: To explore the effects of Chinese herbs for replenishing qi and resolving stagnation on hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in granulation tissue of skin ulcers in rats with syndrome of blood stasis and qi deficiency. METHODS: Diabetic rats with back full-thickness skin lesion and syndrome of blood stasis and qi deficiency were divided in to five groups: untreated group, basic fibroblast growth factor (bFGF) treated group, Yiqi Huayu Recipe (a recipe for replenishing qi and resolving stagnation)-treated group, Yiqi Recipe (a recipe for replenishing qi)-treated group and Huayu Recipe (a recipe for resolving stagnation)-treated group, and another eight normal rats served as normal control group. Immunohistochemical method and image analysis were used to test the expressions of HIF-1alpha and VEGF in granulation tissue of skin ulcers in rats with diabetes. RESULTS: In the untreated group, the expression of HIF-1alpha was significantly increased and the expression of VEGF was significantly decreased as compared with those in the normal control group (P<0.01). The expression of HIF-1alpha was obviously lower (P<0.01) and the expression of VEGF was significantly higher in the four drug treated groups as compared with those in the untreated group. In the Yiqi Huayu Recipe-treated group, the expression of HIF-1alpha was obviously lower than those in the bFGF-treated, Yiqi Recipe-treated and Huayu Recipe-treated groups (P<0.05 or P<0.01), and the expression of VEGF was significantly higher than that in the bFGF-treated group (P<0.01). CONCLUSION: Chinese herbs for replenishing qi and resolving stagnation can promote the wound healing in rats through reducing the expression of HIF-1alpha, accelerating the expression of VEGF in granulation tissue of skin ulcers in rats with diabetes and ameliorating the status of ischemia and hypoxia. PMID- 17352874 TI - [Effects of Huoxue Bushen Mixture on skin blood vessel neogenesis and vascular endothelial growth factor expression in hair follicle of C57BL/6 mice]. AB - OBJECTIVE: To investigate the possible stimulating mechanism of Huoxue Bushen Mixture (HXBSM), a traditional Chinese compound medicine, on hair growth of mice via measuring the variance of skin blood vessel neogenesis and vascular endothelial growth factor (VEGF) expression in the hair follicle. METHODS: Hot rosin and paraffin mixture depilation were used to induce C57BL/6 mice hair follicle to enter from telogen into anagen. Ninety C57BL/6 mice were divided into 3 groups randomly: HXBSM group, Yangxue Shengfa Capsule (YXSFC, another traditional Chinese compound medicine) group and untreated group. The mice were fed with corresponding drugs after modeling. The hair growth of the mice was observed every day. Every ten mice out of each group were executed respectively at day 4, 11 and day 17. Skin blood vessel neogenesis was counted through pathological section and VEGF expression in the hair follicle was measured via immunohistochemical method. RESULTS: The number of local blood vessel neogenisis in the HXBSM group observed was larger than that in the untreated group at day 4 (P<0.05); and evidently larger than that in the YXSFC group and the untreated group at day 11 (P<0.05). The expression of VEGF in the hair follicle was distinctively higher than that in the YXSFC group and the untreated group at day 11 and day 17 (P<0.05). CONCLUSION: HXBSM up-regulates VEGF expression to accelerate blood vessel neogenesis and hair growth. PMID- 17352875 TI - [Impact of Jinhong Tablet on thymus of rats with cholangitis]. AB - OBJECTIVE: To study the changes of the center of cellular immune thymus and the interference of Jinhong Tablet, a compound traditional Chinese herbal medicine, during the course of cholangitis. METHODS: Twenty-four male Wistar rats were randomly divided into three groups. Ligation group, simple ligation of bile duct without producing infection and fed with normal saline; untreated group, reproduce acute cholangitis and fed with normal saline; Jinhong Tablet-treated group, reproduce cholangitis and treated with Jinhong Tablet. Five days after modeling, the rats were sacrificed and the thymus were sampled to observe the morphological changes with an electronic microscope, count the index of thymus and apoptosis and assay the expressions of Bcl-2 gene coding protein and Fas gene coding protein. RESULTS: The frequency of apoptosis of thymus in the untreated group was higher than that in the Jinhong Tablet-treated group and the ligation group, and the frequency of apoptosis of thymus in the Jinhong Tablet-treated group was higher than that in the ligation group. Compared with the Jinhong Tablet-treated group and the ligation group, the weight and index of thymus were lower and the index of apoptosis of thymus was higher significantly in the untreated group (P<0.01). The expression of Bcl-2 gene coding protein in the ligation group and the Jinhong Tablet-treated group were much higher than that in the untreated group (P<0.01), but there were no significant differences of the expression of Fas gene coding protein among the three groups. CONCLUSION: There exists a promotion of non-physiological apoptosis of cellular immune center such as decrease of the weight and the index of thymus and increase of the index of apoptosis of thymus during acute cholangitis, which may be inhibited by up regulation of Bcl-2 gene coding protein with antipyretic and purgative herbs Jinhong Tablet. PMID- 17352876 TI - [Effect of traditional Chinese herbs for nourishing the liver on intracellular free calcium level in gallbladder cells of guinea pigs with gallstones]. AB - OBJECTIVE: To observe the changes of intracellular free calcium level ([Ca(2+)]i) in gallbladder cells of guinea pigs with gallstones so as to study the mechanisms of gallstone formation and the prevention and treatment function of traditional Chinese herbs for nourishing the liver. METHODS: Eighty guinea pigs were randomly divided into four groups, which were normal control group, untreated group, nourishing-liver Chinese drug (NLCD) group and ursodeoxycholic acid (UDCA) group, with 20 guinea pigs in each group. Gallstones were induced in the guinea pigs of the latter 3 groups by the feed of diet inducing cholelithiasis with high cholesterol, while the corresponding medicines were used in NLCD group and UDCA group for prevention and treatment for 7 weeks. Then the state of the guinea pigs, the formation of gallstones, and the changes of [Ca(2+)]i in gallbladder cells were observed. RESULTS: The [Ca(2+)]i in gallbladder cells of guinea pigs in the untreated group was decreased significantly. NLCD improved the behavioral signs of the guinea pigs, significantly decreased the formative rate of gallstones and increased the [Ca(2+)]i in gallbladder cells. CONCLUSIONS: The [Ca(2+)]i in gallbladder cells is the important factor for contractile function of gallbladder and the information of gallstones. Traditional Chinese herbs for nourishing the liver may significantly increase the [Ca(2+)]i in gallbladder cells to facilitate contraction of the smooth muscle cells of gallbladder and relieve the cholestatis. It may be one of the mechanisms of traditional Chinese herbs for nourishing the liver in preventing and treating cholelithiasis. PMID- 17352877 TI - [Conditioned mediums of different rat cerebral microvascular endothelial cells against damage of ischemia and ischemia/reperfusion neurons]. AB - OBJECTIVE: Using the method of lactate dehydrogenase (LDH) assay, to observe the activities of rat cerebral microvascular endothelial cells (CMECs) intervened by Tongluo Jiunao Injection (TLJNI), a traditional Chinese compound drug removing toxin to dredge brain collaterals, and then further study the effects of different kinds of conditioned mediums (CMECs-CM) of cerebral microvascular endothelial cells on ischemia and ischemia/reperfusion cerebral cortex cells, and to probe into the drug pharmacological mechanisms of CMECs in modulating the neurons. METHODS: Three kinds of CMECs (normal, ischemic and ischemic/reperfusional) were all treated by TLJNI previously, and then the three pairs of CMECs-CM without serum were collected respectively for LDH assay. Rat cerebral cortex neurons were also primarily cultured and then divided into similar three groups (normal, ischemic and ischemic/reperfusional). The neuron responses caused by CMECs-CM at different concentrations were observed by using LDH transudation rate assay. RESULTS: The LDH release values of ischemic and ischemic/reperfusional CMECs with TLJNI treatment were obviously reduced (P<0.01) compared with the same kinds of CMECs untreated. For ischemic neurons, both conditioned medium of ischemic CMECs (Is-CM) and conditioned medium of ischemic CMECs with drug treatment (IsT-CM) in high concentration of 100% increased the LDH transudation rate (P<0.01), while in low concentration of 10%, IsT-CM reduced the transudation rate (P<0.05). For ischemia/reperfusion neurons, all kinds of CMECs-CM reduced the transudation rate respectively (P<0.05 or P<0.01). As far as each group concentration was concerned, 10% or 50% showed relatively stronger effects, and both conditioned medium of normal CMECs (N-CM) group and conditioned medium of ischemic/reperfusional CMECs (Rp-CM) group had statistical significance (P<0.05 or P<0.01). For normal neurons, all kinds of CMECs-CM increased the transudation rate respectively (P<0.05 or P<0.01). As far as each group concentration was concerned, only conditioned medium of normal CMECs (N-CM) had statistical significance (P<0.05 or P<0.01). CONCLUSION: The study shows that TLJNI is capable of preventing the damage of CMECs from both ischemia and ischemia/reperfusion states. Chinese drug can restrain the brain ischemia and ischemia/reperfusion damage by the media that CMECs modulate the neurons, demonstrating the pharmacological mechanisms of TLJNI. This work also indicates that there exist some active substances against ischemia/reperfusion injury secreted from CMECs-CM with TLJNI treatment. PMID- 17352878 TI - [Effects of heterogenous suberect spatholobus stem on peripheral blood cell counts of 60Co gamma ray irradiated mice]. AB - OBJECTIVE: To investigate the effects of heterogenous suberect spatholobus stem (Spatholobus suberectu, Mucuna birdwoodiana, Millettia oosperma and Millettia dielsiana) on peripheral blood cell counts of mice with bone marrow suppression induced by (60)Co gamma ray irradiation. METHODS: Bone marrow suppression was induced by sublethal dose of (60)Co gamma ray in mice. White blood cell (WBC), red blood cell (RBC) and platelet (PLT) counts in peripheral blood of the mice were detected one day, 3, 7, 14 and 21 days after intragastric administration of different doses of the four kinds of suberect spatholobus stem, respectively. RESULTS: A slowdown of the decrease of WBC, RBC and PLT counts in peripheral blood of the mice with bone marrow suppression was observed after intragastric administration. The WBC, RBC and PLT counts in the Mucuna birdwoodiana-treated and Spatholobus suberectu-treated groups were significantly higher than those in the untreated group (P<0.05). CONCLUSION: All the four kinds of heterogenous suberect spatholobus stem can accelerate the recovery of WBC, RBC and PLT counts in peripheral blood of mice with bone marrow suppression, while the effects of Spatholobus suberectu and Mucuna birdwoodiana are relatively good. PMID- 17352879 TI - [Comparison of tunnel thread-drawing therapy and fistulectomy therapy for low complex anal fistula]. PMID- 17352880 TI - [Assessing breast cancer risk in women with mammary hyperplasia of different syndromes using mammography]. PMID- 17352881 TI - [Professor Han-jun Tang's experience in treating lymphadenopathy with Yin and Yang theory]. PMID- 17352882 TI - [Experience of Professor Han-jun Tang in treating breast cancer after operation based on syndrome differentiation]. PMID- 17352883 TI - [Treatment of chronic skin ulcers with traditional Chinese medicine: a report of five cases]. PMID- 17352884 TI - [Research on association between insulin resistance and cholelithiasis: a review]. PMID- 17352885 TI - [Influencing factors and psychotherapies of psychogenic problems in breast cancer patients]. PMID- 17352886 TI - [Application of statistical idea and the triple-type theory in the scientific research of biomedicine]. PMID- 17352887 TI - [Thinking on English translation of traditional Chinese Medicine]. PMID- 17352890 TI - Multitasking: how much is too much? PMID- 17352891 TI - Total anomalous pulmonary venous connection. AB - Total anomalous pulmonary venous connection (TAPVC) is a congenital heart defect in which there is no connection between the pulmonary veins and the left atrium. An anomalous connection is established that allows the pulmonary veins to deliver pulmonary venous blood to the right side of the heart rather than to the left side. A patent foramen ovale or an atrial septal defect develops in utero, allowing a right-to-left shunting of blood without which the infant would die. This article describes normal embryology, abnormal embryology that results in TAPVC, types of anomalous connections, how TAPVC is diagnosed, surgical correction, and nursing interventions when caring for patients with TAPVC and dealing with the concerns of their family members. PMID- 17352892 TI - Factors influencing perioperative nurses' error reporting preferences. AB - To explore the influence of scope of practice and patient outcomes on error reporting, 13 nurses were interviewed after they reviewed four "error" scenarios ranging in both scope of practice and seriousness of outcome. Of 52 theoretical incidents, only 30 were identified as errors. The nurses indicated they would formally report errors for only eight of the incidents. For another 10 incidents, the nurses would have reported using an informal reporting system only. Qualitative analysis of the interviews revealed that perceived scope of practice influenced reporting preferences, and seriousness of outcome was only a secondary consideration. Selective error reporting and the reasons for selective reporting have negative implications for patient safety. PMID- 17352893 TI - Perioperative care of the immunocompromised patient. AB - Immunity refers to the body's capacity to resist invading organisms and toxins, thereby preventing tissue and organ damage. A patient whose immune system is impaired may be at higher risk for untoward perioperative events. Some populations most at risk for immunocompromise include infants, geriatric patients, people who have undergone organ transplantation, and people with cancer. Patients who are immunocompromised have an increased risk for hypothermia, which can affect postoperative wound healing processes and can increase the risk of wound infection. This article provides a basic overview of the immune system, a discussion of common disorders and diseases of the immune system, and a guide for perioperative nurses to use when they care for a patient who is immunocompromised. PMID- 17352894 TI - Loaner instrumentation: processing the unknown. AB - The use of loaner instrumentation is a growing phenomenon in today's expanding health care environment. Central processing department personnel at Walter Reed Medical Center, Washington, DC, undertook a project to determine if loaner instrumentation coming into the facility had been decontaminated. Sixteen percent of the loaner instruments tested were positive for blood residue. The results of this project were used to strengthen internal standard operating procedures and to alert the hospital's infection control committee of a potential safety problem. PMID- 17352895 TI - Distance learning and perioperative nursing. AB - Distance learning in nursing education is arriving with unprecedented speed, which has led to much uncertainty among educators. This article provides an overview of distance learning and its application to perioperative nursing. Lack of face-to-face interaction is of foremost concern in distance learning, and educators must develop new teaching strategies to address this problem. Models for assessing outcomes and effectiveness are important tools to use when implementing a distance learning program. Basic perioperative nursing concepts, skills, procedures, and recommended practices can be introduced effectively with online distance learning modalities and then reinforced through a clinical component. PMID- 17352896 TI - Does preoperative anxiety level predict postoperative pain? AB - Preoperative anxiety is a common component of the surgical experience, and increased levels of anxiety may alter a patient's surgical course and cause increased postoperative pain. A review of the literature was undertaken to evaluate the presence and significance of any correlation between preoperative anxiety and postoperative pain. Although inconsistency was found in the articles that were reviewed, most of the available evidence revealed a positive correlation between preoperative anxiety and postoperative pain. Further studies should be conducted to establish the correlation between preoperative anxiety and postoperative pain and to determine appropriate nursing interventions. PMID- 17352898 TI - Caution: tubing misconnections can be deadly. PMID- 17352901 TI - Genetics of morphogenesis and pathogenic development of Ustilago maydis. AB - Ustilago maydis has emerged as an important model system for the study of fungi. Like many fungi, U. maydis undergoes remarkable morphological transitions throughout its life cycle. Fusion of compatible, budding, haploid cells leads to the production of a filamentous dikaryon that penetrates and colonizes the plant, culminating in the production of diploid teliospores within fungal-induced plant galls or tumors. These dramatic morphological transitions are controlled by components of various signaling pathways, including the pheromone-responsive MAP kinase and cAMP/PKA (cyclic AMP/protein kinase A) pathways, which coregulate the dimorphic switch and sexual development of U. maydis. These signaling pathways must somehow cooperate with the regulation of the cytoskeletal and cell cycle machinery. In this chapter, we provide an overview of these processes from pheromone perception and mating to gall production and sporulation in planta. Emphasis is placed on the genetic determinants of morphogenesis and pathogenic development of U. maydis and on the fungus-host interaction. Additionally, we review advances in the development of tools to study U. maydis, including the recently available genome sequence. We conclude with a brief assessment of current challenges and future directions for the genetic study of U. maydis. PMID- 17352903 TI - Genomics of the plant pathogenic oomycete Phytophthora: insights into biology and evolution. AB - The genus Phytophthora includes many destructive pathogens of plants. Although having "fungus-like" appearances, Phytophthora species reside in a eukaryotic kingdom separate from that of true fungi. Distinct strategies are therefore required to study and defend against Phytophthora. Large sequence databases have recently been developed for several species, and tools for functional genomics have been enhanced. This chapter will review current progress in understanding the genome and transcriptome of Phytophthora, and provide examples of how genomics resources are advancing molecular studies of pathogenesis, development, transcription, and evolution. A better understanding of these remarkable pathogens should lead to new approaches for managing their diseases. PMID- 17352902 TI - Enabling a community to dissect an organism: overview of the Neurospora functional genomics project. AB - A consortium of investigators is engaged in a functional genomics project centered on the filamentous fungus Neurospora, with an eye to opening up the functional genomic analysis of all the filamentous fungi. The overall goal of the four interdependent projects in this effort is to accomplish functional genomics, annotation, and expression analyses of Neurospora crassa, a filamentous fungus that is an established model for the assemblage of over 250,000 species of non yeast fungi. Building from the completely sequenced 43-Mb Neurospora genome, Project 1 is pursuing the systematic disruption of genes through targeted gene replacements, phenotypic analysis of mutant strains, and their distribution to the scientific community at large. Project 2, through a primary focus in Annotation and Bioinformatics, has developed a platform for electronically capturing community feedback and data about the existing annotation, while building and maintaining a database to capture and display information about phenotypes. Oligonucleotide-based microarrays created in Project 3 are being used to collect baseline expression data for the nearly 11,000 distinguishable transcripts in Neurospora under various conditions of growth and development, and eventually to begin to analyze the global effects of loss of novel genes in strains created by Project 1. cDNA libraries generated in Project 4 document the overall complexity of expressed sequences in Neurospora, including alternative splicing alternative promoters and antisense transcripts. In addition, these studies have driven the assembly of an SNP map presently populated by nearly 300 markers that will greatly accelerate the positional cloning of genes. PMID- 17352904 TI - Sex and virulence of human pathogenic fungi. AB - Over the past decade, opportunistic fungal infectious diseases have increased in prevalence as the population of immunocompromised individuals escalated due to HIV/AIDS and immunosuppression associated with organ transplantation and cancer therapies. In the three predominant human pathogenic fungi (Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus), a unifying feature is that all three retained the machinery needed for sex, and yet all limit their access to sexual reproduction. While less well characterized, many of the other human pathogenic fungi also appear to have the ability to undergo sexual reproduction. Recent studies with engineered pairs of diploid strains of the model yeast Saccharomyces cerevisiae, one that is sexual and the other an obligate asexual, provide direct experimental validation of the benefits of both sexual and asexual reproduction. The obligate asexual strain had an advantage in response to constant environmental conditions whereas the sexual strain had a competitive edge under stressful conditions (Goddard et al., 2005; Grimberg and Zeyl, 2005). The human pathogenic fungi have gone to great lengths to maintain all of the machinery required for sex, including the mating-type locus and the pheromone response and cell fusion pathways. Yet these pathogens limit their access to sexual or parasexual reproduction in unique and specialized ways. Our hypothesis is that this has enabled the pathogenic fungi to proliferate in their environmental niche, but to also undergo genetic exchange via sexual reproduction in response to stressful conditions such as new environments, different host organisms, or changes in the human host such as antimicrobial therapy. Further study of the sexual nature of the human pathogenic fungi will illuminate how these unique microbes have evolved into successful pathogens in humans. PMID- 17352905 TI - From genes to genomes: a new paradigm for studying fungal pathogenesis in Magnaporthe oryzae. AB - Magnaporthe oryzae is the most destructive fungal pathogen of rice worldwide and because of its amenability to classical and molecular genetic manipulation, availability of a genome sequence, and other resources it has emerged as a leading model system to study host-pathogen interactions. This chapter reviews recent progress toward elucidation of the molecular basis of infection-related morphogenesis, host penetration, invasive growth, and host-pathogen interactions. Related information on genome analysis and genomic studies of plant infection processes is summarized under specific topics where appropriate. Particular emphasis is placed on the role of MAP kinase and cAMP signal transduction pathways and unique features in the genome such as repetitive sequences and expanded gene families. Emerging developments in functional genome analysis through large-scale insertional mutagenesis and gene expression profiling are detailed. The chapter concludes with new prospects in the area of systems biology, such as protein expression profiling, and highlighting remaining crucial information needed to fully appreciate host-pathogen interactions. PMID- 17352907 TI - Fungal genomics: a tool to explore central metabolism of Aspergillus fumigatus and its role in virulence. AB - Aspergillus fumigatus is an opportunistic pathogenic fungus that primarily infects neutropenic animal hosts. This fungus is found throughout the world, can utilize a wide range of substrates for carbon and nitrogen sources, and is capable of growing at elevated temperatures. The ability to grow at high temperatures and utilize a range of nutrient substrates for growth potentially contributes to this being the number one human pathogenic mold worldwide. The recently completed genome sequence for this fungus creates an opportunity to examine how central metabolic pathways and their regulation contribute to pathogenesis. A review of the existing literature illustrates that genes involved in the biosynthesis of key nutrients are essential for pathogenesis in A. fumigatus. In addition, nutrient sensing and regulation of biosynthetic pathways also contribute to fungal pathogenesis. The advent of improved methods for manipulating the genome of A. fumigatus, along with the completed genome sequence, now make it feasible to investigate the role of all metabolic pathways and control of these pathways in fungal virulence. PMID- 17352906 TI - Genetic and genomic dissection of the Cochliobolus heterostrophus Tox1 locus controlling biosynthesis of the polyketide virulence factor T-toxin. AB - Fungal pathogenesis to plants is an intricate developmental process requiring biological components found in most fungi, as well as factors that are unique to fungal taxa that participate in particular fungus-plant interactions. The host selective polyketide toxin known as T-toxin produced by Cochliobolus heterostrophus race T, a highly virulent pathogen of maize, is an intriguing example of the latter type of virulence determinant. The Tox1 locus, which controls biosynthesis of T-toxin, originally defined as a single genetic locus, it is, in fact, two exceedingly complex loci on two chromosomes that are reciprocally translocated with respect to their counterparts in weakly pathogenic race O. Race O lacks the Tox1 locus and does not produce T-toxin. Highly virulent race T was first recognized when it caused an epidemic of Southern Corn Leaf Blight, which devastated the US corn crop in 1970. The evolutionary origin of the Tox1 locus remains unknown. PMID- 17352909 TI - Strain collections and genetic nomenclature. AB - The ease of rapidly accumulating a large number of mutants requires careful bookkeeping to avoid confusing one mutant with another. Each mutant constructed should be assigned a strain number. Strain numbers usually consist of two to three capital letters designating the lab where they were constructed and a serial numbering of the strains in a central laboratory collection. Every mutation should be assigned a name that corresponds to a particular gene or phenotype, and an allele number that identifies each specific isolate. When available for a particular group of bacteria, genetic stock centers are the ultimate resources for gene names and allele numbers. Examples include the Salmonella Genetic Stock Centre ( http://www.ucalgary.ca/~kesander/), and the E. coli Genetic Stock Center (http://cgsc.biology.yale.edu/). It is also important to indicate how the strain was constructed, the parental (recipient) strain, and the source of any donor DNA transferred into the recipient strain (Maloy et al., 1996). PMID- 17352910 TI - Use of antibiotic-resistant transposons for mutagenesis. AB - One of the greatest advances in molecular genetics has been the application of selectable transposons in molecular biology. After 30 years of use in microbial genetics studies, transposons remain indispensable tools for the generation of null alleles tagged with selectable markers, genetic mapping, manipulation of chromosomes, and generation of various fusion derivatives. The number and uses of transposons as molecular tools continues to expand into new fields such as genome sciences and molecular pathogenesis. This chapter outlines some of the many uses of transposons for molecular genetic analysis and strategies for their use. PMID- 17352911 TI - In vivo mutagenesis using EZ-Tn5. AB - Epicentre Biotechnologies has developed a suite of transposon-based tools for use in modern bacterial genetics. This chapter highlights the EZ-Tn5 Transposome system and focuses on in vivo mutagenesis and subsequent rescue cloning. Many other applications and variations have been described and are available through Epicentre's website at http://www.epibio.com/. PMID- 17352912 TI - Identification of essential genes in bacteria. AB - Essential genes are identified in duplicated regions of the bacterial chromosome. Transposition of a vector that forms operon fusions into a strain carrying a chromosomal duplication allows insertion of the transposon into essential genes because a second copy of the essential gene is present. When the duplication is allowed to segregate, only the segregant that carries the copy of the intact essential gene survives. The transposon insertion in the essential gene is maintained only in the duplication derivatives. A technique is described that uses a Tn10 derivative, Tn10dTc-araC(+), which contains a cloned copy of the Escherichia coli araC(+) gene, as a portable region of homology to generate large duplications of the Salmonella chromosome. The duplication is maintained in the population by growth in the presence of tetracycline. When the lac operon fusion vector, MudJ, is transposed into the duplicated region, removal of tetracycline from the growth media allows segregation of the duplication yielding (Ara(-)) haploid segregants which appear as red colonies or as red/white (Ara(-/+)) sectoring colonies on TTC arabinose indicator plates. However, if the insertion is in an essential gene, only segregants that lose the MudJ insertion in the essential gene survive. In this case, selection for the insertion in the essential gene yields solid white (Ara(+)) colonies in the absence of tetracycline. While the specific design presented uses Mud transposon insertions to generate lac operon (transcriptional) and lacZ gene (translational) fusions to essential genes, this technique can be used to generate transposon insertions of any kind into essential genes. PMID- 17352913 TI - Isolation of transposon insertions. AB - Transposon insertions in and near a gene of interest facilitate the genetic characterization of a gene in vivo. This chapter is dedicated to describing the isolation of mini-Tn10 insertions in any desired nonessential gene in Salmonella enterica, as well as the isolation of mini-Tn10 insertions near particular genes. The protocols describe use of a tetracycline-resistant Tn10 derivative, but similar approaches can be used for derivatives resistant to other antibiotics. In addition, these approaches are directly applicable to other bacteria that have generalized transducing phages. PMID- 17352914 TI - Localized mutagenesis. AB - Localized mutagenesis can be used to obtain mutants in genes of interest based on linkage to selectable markers. Mutagens diethylsulfate and hydroxylamine are used to obtain predominantly transition mutations in the DNA either by whole chromosomal mutagenesis or mutagenesis of DNA isolated as purified plasmid or packaged in transducing phage particles. Selectable markers can include those based on auxotrophic requirements, carbon or nitrogen source utilization, or antibiotic resistance markers, such as those encoded in transposons. PMID- 17352915 TI - Generation of deletions and duplications using transposons as portable regions of homology with emphasis on mud and Tn10 transposons. AB - In bacteria complementation and dominance testing requires the establishment of a diploid state for the gene of interest. In addition, it is often desirable to characterize reporter fusion constructs in strains with both the reporter fusion and an intact gene copy present in single copy. Transposons provide portable regions of homology to facilitate construction of targeted chromosomal rearrangements such as deletions and duplications. The properties of the large Mud transposons, MudA and MudB allow for the direct duplication and deletion of virtually any region of the Salmonella enterica chromosome between the points of two Mud insertions in a simple bacteriophage P22 transductional cross. Furthermore, duplication construction will be described for the generation of strains with a lac operon transcriptional fusion or lacZ gene translational fusion to any gene of interest at the join-point of the duplication with a second intact copy of the gene of interest located in tandem single copy in the same chromosome. In addition, methods for generation of tandem chromosomal duplications using transposon Tn10 as portable regions of homology are presented. These allow construction of strains duplicated for any gene of interest in tandem, single copy on the chromosome to allow for complementation and dominance testing for alleles for virtually any gene. PMID- 17352916 TI - Target-directed proteolysis in vivo. AB - The experimental problems associated with in vivo studies of essential proteins or integral membrane proteins have triggered geneticists to generate novel approaches that have often led to insights of general relevance (Shuman and Silhavy, 2003). In order to extend the experimental portfolio, we developed target-directed proteolysis (TDP), an in vivo method allowing structural and functional characterization of target proteins in living cells. TDP is based on the activity of the highly sequence-specific NIa protease from tobacco etch virus. When its recognition site of seven residues is engineered into target proteins and NIa protease is expressed under tight promoter control, substrates can be conditionally processed while other cellular proteins remain unaffected. Applications include conditional inactivation as well as functional characterization of target proteins. PMID- 17352917 TI - Sets of transposon-generated sequence-tagged mutants for structure-function analysis and engineering. AB - Various genetic strategies are available for the isolation of small, in-frame insertional mutants. Here, we summarize some of the ways in which the resulting mutant libraries in particular genes have been used for the analysis of protein structure-function relationships and in engineering applications. PMID- 17352918 TI - Using genomic microarrays to study insertional/transposon mutant libraries. AB - The rapid expanse of microbial genome databases provides incentive and opportunity to study organismal behavior at the whole-genome level. While many newly sequenced genes are assigned names based on homology to previously characterized genes, many putative open reading frames remain to be annotated. The use of microarrays enables functional characterization of the entire genome with respect to genes important for different growth conditions including nutrient deprivation, stress responses, and virulence. The methods described here combine advancements in the identification of genomic sequences flanking insertional mutants with microarray methodology. The combination of these methods facilitates tracking large numbers of mutants for phenotypic studies. This improves both the efficiency of genome-saturating library screens and contributes to the functional annotation of unknown genes. PMID- 17352919 TI - Screening transposon mutant libraries using full-genome oligonucleotide microarrays. AB - The experimental details for a high-throughput microarray-based screening technique for both detecting and mapping Tn5 insertion mutants in parallel within a library are presented. Following Tn5 mutagenesis, viable mutants are pooled and grown competitively under selective conditions. Chromosomal DNA is then isolated from each mutant pool. Biotin-labeled run-off in vitro RNA transcripts, representing the neighboring chromosomal DNA for each insertion remaining in the population, are generated using T7 promoters located at the ends of the transposon. Custom-designed, whole-genome oligonucleotide microarrays are used to analyze the labeled RNA transcripts and to detect each mutant in the library. Microarray data comparisons for each growth condition allow the identification of mutants that failed to survive the imposed growth selection. In addition, due to the density of the microarrays the genomic locations of the individual transposon insertions within each library can be identified to within 50 base pairs. Details for the in vivo Tn5 mutagenesis procedure, mutant library construction and competitive outgrowth, T7 in vitro transcription/labeling, and microarray data analysis will be provided. PMID- 17352920 TI - Creating recombination-activated genes and sequence-defined mutant libraries using transposons. AB - The properties of a collection of transposon Tn5 derivatives that generate reporter gene fusions and internal protein tags are summarized. Procedures utilizing several of the transposons for generating genes activated by Cre-loxP recombination and for creating large sequence-defined mutant libraries are described in detail. PMID- 17352921 TI - Use of operon and gene fusions to study gene regulation in Salmonella. AB - Coupling the expression of a gene with an easily assayable reporter gene provides a simple genetic trick for studying the regulation of gene expression. Two types of fusions between a gene and a reporter gene are possible. Operon fusions place the transcription of a reporter gene under the control of the promoter of a target gene, but the translation of the reporter gene and target gene are independent; gene fusions place the transcription and translation of a reporter gene under the control of a target gene, and result in a hybrid protein. Such fusions can be constructed in vitro using recombinant DNA techniques or in vivo using transposon derivatives. Many different transposon derivatives are available for constructing operon and gene fusions, but two extremely useful fusion vectors are (1) Mu derivatives that form operon and gene fusions to the lacZ gene, and (2) Tn5 derivative that forms gene fusions to the phoA gene. PMID- 17352922 TI - Genomic screening for regulatory genes using the T-POP transposon. AB - The identification of a gene that activates or regulates a gene or regulon of interest often requires the artificial induction of the regulatory gene. The properties of the Tn10-derived transposon T-POP allow a simple chromosomal survey of genes that, when artificially induced from an adjacent T-POP transposon by the addition of tetracycline, can activate or inhibit the expression of virtually any gene of interest. Procedures for genome-wide screening for T-POP inducible regulatory genes are described in detail. T-POP is a derivative of transposon Tn10dTc. It encodes resistance to tetracycline, but unlike Tn10dTc, the tet(A) and tet(R) promoters do not terminate within the transposon. Instead they continue out into adjacent chromosomal DNA. When this element inserts in a gene, three things will result: (1) the target gene is disrupted by the addition of a large block of DNA (approximately 3000 bases); (2) a drug-resistance gene (tetracycline resistance) included in the inserted material is now 100% linked to the insertion mutant phenotype; and (3) the mRNA transcripts initiated at either the tet(A) or tet(R) promoters (or both) will continue out into the adjacent chromosomal DNA. Despite the fancy aspects, insertion mutants are easy to isolate and can be assayed for effects on gene regulation using simple plate tests. PMID- 17352923 TI - Recombineering: in vivo genetic engineering in E. coli, S. enterica, and beyond. AB - "Recombineering," in vivo genetic engineering with short DNA homologies, is changing how constructs are made. The methods are simple, precise, efficient, rapid, and inexpensive. Complicated genetic constructs that can be difficult or even impossible to make with in vitro genetic engineering can be created in days with recombineering. DNA molecules that are too large to manipulate with classical techniques are amenable to recombineering. This technology utilizes the phage lambda homologous recombination functions, proteins that can efficiently catalyze recombination between short homologies. Recombineering can be accomplished with linear PCR products or even single-stranded oligos. In this chapter we discuss methods of and ways to use recombineering. PMID- 17352924 TI - lambda-Red genetic engineering in Salmonella enterica serovar Typhimurium. AB - The use of the recombination system from bacteriophage lambda, lambda-Red, allows for PCR-generated fragments to be targeted to specific chromosomal locations in sequenced genomes. A minimal region of homology of 30 to 50 bases flanking the fragment to be inserted is all that is required for targeted mutagenesis. Procedures for creating specific insertions, deletions, and site-directed changes are described. PMID- 17352925 TI - Probing nucleoid structure in bacteria using phage lambda integrase-mediated chromosome rearrangements. AB - Conservative site-specific recombination has been adapted for a multitude of uses, in both prokaryotes and eukaryotes, including genetic engineering, expression technologies, and as probes of chromosome structure and organization. In this article, we give a specific example of the latter application, and a quick summary of some of the myriad other genetic and biotechnology applications of site-specific recombination. PMID- 17352926 TI - Dissecting nucleic acid-protein interactions using challenge phage. AB - The bacteriophage P22-based challenge system is a sophisticated genetic tool for the characterization of sequence-specific recognition of DNA and RNA in vivo. The construction of challenge phage follows simple phage lysate preparations and detection of constructs by positive selection methods for plaques on selective strains. The challenge phage system is a powerful tool for the characterization of protein-DNA and protein-RNA interactions in vivo. The challenge phage has been further developed to characterize the interactions of multiple proteins in heteromultimeric complexes that are required for DNA binding. Under appropriate conditions, expression of the ant gene determines the lysis-lysogeny decision of P22. This provides a positive selection for and against DNA binding: repression of ant can be selected by requiring growth of lysogens, and mutants that cannot repress ant can be selected by requiring lytic growth of the phage. Thus, placing ant gene expression under the control of a specific DNA-protein interaction provides very strong genetic selections for regulatory mutations in the DNA binding protein and DNA-binding site that either increase or decrease the apparent strength of a DNA-protein interaction in vivo. Furthermore, the challenge phage contains a kanamycin-resistance element that can be used to either directly select for lysogeny or to determine the frequency of lysogeny for a given protein-DNA interaction to measure the efficiency of DNA binding in vivo. Selection for lysogeny can be used to isolate DNA-binding proteins with altered or enhanced DNA-binding specificities. The challenge phage selection provides a general method for identifying critical residues involved in DNA-protein interactions. Challenge phage selections have been used to genetically dissect many different prokaryotic and eukaryotic DNA-binding interactions. PMID- 17352927 TI - Mud-P22. AB - Mud-P22 derivatives are hybrids between phage Mu and P22 that can be inserted at essentially any desired site on the Salmonella chromosome (Benson and Goldman, 1992; Youderian et al., 1988). Induction of Mud-P22 insertions yields phage particles that, as a population, carry chromosomal DNA from the region between 150 and 250Kb on one side of the insertion. Thus, phage lysates from a representative set of Mud-P22 insertions into the S. typhimurium chromosome yield an ordered library of DNA that provides powerful tools for the genetic and physical analysis of the Salmonella genome. Although Mud-P22 has not yet been used in other species, this approach should be applicable in a variety of other bacteria as well. PMID- 17352928 TI - Phage metagenomics. AB - The vast majority of novel DNA sequences deposited in the databases now comes from environmental phage DNA sequences. Methods are presented for the cloning and sequencing of phage DNA that might otherwise be lethal to bacterial host vectors or contain modified DNA bases that prevent standard cloning of such sequences. In addition, methods are presented for the isolation of viral particles directly from soil and sediment environmental samples or from large volumes of environmental water samples. The viral particles are then purified by cesium chloride density centrifugation followed by DNA extraction. This purified viral metagenomic DNA is then used for cloning and sequencing. PMID- 17352929 TI - Proceedings of the 2nd World Congress on Huntington's Disease, 11-13 September 2005, Manchester, England, UK. PMID- 17352930 TI - Genetic criteria for Huntington's disease pathogenesis. AB - Genetic analysis aims to identify the variations in DNA sequence whose functional consequences produce heritable variations in phenotype. In one of the first successes of unbiased molecular genetic analysis in human disease, the Huntington's disease (HD) gene was mapped and cloned without any prior knowledge of the nature of its protein product or of the molecular defect that underlies the characteristic phenotype of the disorder. However, while the cloning of HD and recognition of its trinucleotide repeat expansion spawned a plethora of approaches to investigating HD through its distinctive neuropathology, the role for genetic strategies in HD research did not end there. The use of genetic analysis has remained a critical tool for defining the characteristics of the mechanism that triggers the pathogenic process, permitting the investigation of early events that occur long before traditionally recognized pathology. Delineation of these events can reveal molecular targets for development of therapies that prevent onset of HD. Most recently, an extension of genetic analysis to the identification of non-linked genetic variations that alter the course of HD pathogenesis has offered the promise of identifying modifier genes to reveal biological pathways active throughout the disease process and to provide valid targets for pharmacological intervention. Thus, unbiased genetic strategies have not only provided a crucial entree into molecular investigation of HD via a root cause that was previously unsuspected, they also represent a continuing route to accelerate the ultimate goal of developing an effective treatment for HD. PMID- 17352931 TI - The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypes. AB - The identification of the Huntington's disease (HD) mutation as a CAG/polyglutamine repeat expansion enabled the generation of transgenic rodent models and gene-targeted mouse models of HD. Of these, mice that are transgenic for an N-terminal huntingtin fragment have been used most extensively because they develop phenotypes with relatively early ages of onset and rapid disease progression. Although the fragment models have led to novel insights into the pathophysiology of HD, it is important that models expressing a mutant version of the full-length protein are analysed in parallel. We have generated congenic C57BL/6 and CBA strains for the HdhQ150 knock-in mouse model of HD so that homozygotes can be analysed on an F1 hybrid background. Although a significant impairment in grip strength could be detected from a very early age, the performance of these mice in the quantitative behavioural tests most frequently used in preclinical efficacy trials indicates that they are unlikely to be useful for preclinical screening using a battery of conventional tests. However, at 22 months of age, the Hdh(Q150/Q150) homozygotes showed unexpected widespread aggregate deposition throughout the brain, transcriptional dysregulation in the striatum and cerebellum and decreased levels of specific chaperones, all well characterised molecular phenotypes present in R6/2 mice aged 12 weeks. Therefore, when strain background and CAG repeat length are controlled for, the knock-in and fragment models develop comparable phenotypes. This supports the continued use of the more high-throughput fragment models to identify mechanisms of pathogenesis and for preclinical screening. PMID- 17352932 TI - Progressive CAG expansion in the brain of a novel R6/1-89Q mouse model of Huntington's disease with delayed phenotypic onset. AB - Transgenic models representing Huntington's disease (HD) have proved useful for understanding the cascade of molecular events leading to the disease. We report an initial characterisation of a novel transgenic mouse model derived from a spontaneous truncation event within the R6/1 transgene. The transgene is widely expressed, carries 89 CAG repeats and the animals exhibit a significantly milder neurological phenotype with delayed onset compared to R6/1. Moreover, we report evidence of progressive somatic CAG expansions in the brain starting at an early age before an overt phenotype has developed. This novel line shares a common genetic ancestry with R6/1, differing only in CAG repeat number, and therefore, provides an additional tool with which to examine early molecular and neurophysiological changes in HD. PMID- 17352933 TI - Abnormal cortical synaptic plasticity in a mouse model of Huntington's disease. AB - Huntington's disease is a fatal neurodegenerative disorder characterised by a progressive motor, psychiatric and cognitive decline and associated with a marked loss of neurons in the cortex and striatum of affected individuals. The disease is inherited in an autosomal dominant fashion and is caused by a trinucleotide (CAG) repeat expansion in the gene encoding the protein huntingtin. Predictive genetic testing has revealed early cognitive deficits in asymptomatic gene carriers such as altered working memory, executive function and recognition memory. The perirhinal cortex is believed to process aspects of recognition memory. Evidence from primate studies suggests that decrements in neuronal firing within this cortical region encode recognition memory and that the underlying mechanism is an activity-dependent long-term depression (LTD) of excitatory neurotransmission, the converse of long-term potentiation (LTP). We have used the R6/1 mouse model of HD to assess synaptic plasticity in the perirhinal cortex. This mouse model provides an ideal tool for investigating early and progressive changes in synaptic function in HD. We report here that LTD at perirhinal synapses is markedly reduced in R6/1 mice. We also provide evidence to suggest that a reduction in dopamine D2 receptor signalling may be implicated. PMID- 17352934 TI - Depletion of Complexin II does not affect disease progression in a mouse model of Huntington's disease (HD); support for role for complexin II in behavioural pathology in a mouse model of HD. AB - Huntington's disease (HD) is a progressive, inherited, neurological disorder with a complicated phenotype that is characterised by movement abnormalities, cognitive impairments and psychiatric symptoms. Although HD is a neurodegenerative disease, recent evidence indicates that neurological dysfunction, rather than frank neurodegeneration contributes to, and may even cause early symptoms in the absence of neurodegeneration. One protein that may contribute to neurological dysfunction in HD is complexin II. Complexins are presynaptic proteins that are believed to modulate neurotransmitter release. Complexin II levels are reduced in human HD striatum and cortex, and a progressive depletion of complexin II mRNA and protein has also been shown in the R6/2 mouse model of HD. Interestingly, complexin II knockout mice share behavioural deficits in reversal learning in common with R6/2 mice. Further, the two strains both show abnormalities in long-term potentiation. This evidence led us to wonder whether or not loss of complexin II underlies some of the behavioural deficits seen in R6/2 mice. To investigate this, we crossbred complexin II knockout mice with R6/2 mice to generate a double mutant mouse. The behavioural phenotype of R6/2 mice on a null complexin II background was characterised and was compared to that seen in control mice. Complete knockout of complexin II did not significantly affect the phenotype of R6/2 mice. This indicates that loss of complexin II is part of the mechanism underlying the R6/2 phenotype. Whether it is causal or compensatory remains to be determined. PMID- 17352935 TI - Testing the possible inhibition of proteasome by direct interaction with ubiquitylated and aggregated huntingtin. AB - An impairment of the ubiquitin-proteasome system (UPS) has been postulated in Huntington's disease (HD) and in other CAG-triplet repeat disorders. This hypothesis arises from the observation that polyglutamine (polyQ)-containing inclusion bodies that are characteristic of these diseases also contain components of the UPS. However, since that initial discovery, the UPS impairment hypothesis has remained controversial. Recent in vitro enzymatic studies revealed the inability of eukaryotic proteasomes to digest expanded polyQ, thus suggesting that occasional failure of polyQ to exit the proteasome may interfere with its proteolytic function. However, it has also recently been found that in vitro assembled aggregates made of synthetic polyQ fail to inhibit proteasome activity. Here we propose future experiments that may help to ellucidate whether a direct interaction between proteasomes and polyQ stretches or aggregates can result in inhibition of proteasome activity. PMID- 17352936 TI - Selective degeneration in YAC mouse models of Huntington disease. AB - Huntington disease (HD) is one of at least nine polyglutamine disorders caused by a CAG expansion in the coding region of a disease-causing gene. These disorders are characterized by selective degeneration of different regions of the brain, which is not explained by the expression pattern of the mutant protein. In HD, degeneration primarily occurs in the striatum and cortex. To examine the mechanisms responsible for the selective neuronal loss in HD, we have generated yeast artificial chromosome (YAC) transgenic models of HD that express full length mutant huntingtin (htt) from a YAC. These mice have appropriate tissue specific and temporal expression of mutant htt and accordingly recapitulate the motor deficits, cognitive impairment and selective degeneration of HD. As in human patients, mutant htt expression is not increased in the affected regions of the brain. In contrast, detection of mutant htt in the nucleus is earliest and greatest in the striatum, the region most affected in HD, suggesting that selective nuclear localization of mutant htt may contribute to the region specific atrophy in these mice. Selective phosphorylation of mutant htt on serine 421 may also contribute, as phosphorylation of mutant htt reduces its toxicity and is decreased in the striatum compared to other regions of the brain. Finally, the fact that mutant htt expression increases the susceptibility of striatal neurons to excitotoxicity but not neurons from the cerebellum, suggests that altered sensitization to excitotoxic death may also contribute to selective degeneration in YAC mice. Overall, YAC mice recapitulate the region specific damage that occurs in HD and provide a suitable model for examining the mechanisms underlying of selective degeneration. PMID- 17352937 TI - Cell transplantation for Huntington's disease Should we continue? AB - Cell transplantation for Huntington's disease has developed over the last decade to clinical application in pilot trials in the USA, France and the UK. Although the procedures are feasible, and under appropriate conditions safe, evidence for efficacy is still limited, which has led to some calls that further development should be discontinued. We review the background of striatal cell transplantation in experimental animal models of Huntington's disease and the rationale for applying similar strategies in the human disease, and we survey the present status of the preliminary studies that have so far been undertaken in patients. When we consider the variety of parameters and principles that remain poorly defined -- such as the optimal source, age, dissection, preparation, implantation, immunoprotection and assessment protocols -- it is not surprising that clinical efficacy is still unreliable. However, since these protocols are all tractable to experimental refinement, we consider that the potential for cell transplantation in Huntington's disease is greater than has yet been realised, and remains a therapeutic strategy worthy of investigation and pursuit. PMID- 17352938 TI - Imaging microglial activation in Huntington's disease. AB - Activated microglia have been proposed to play a major role in the pathogenesis of Huntington's Disease (HD). PK11195 is a ligand which binds selectively to peripheral benzodiazepine binding sites, a type of receptor selectively expressed by activated microglia in the central nervous system. Using (11)C-(R)-PK11195 positron emission tomography (PET), we have recently shown in vivo evidence of increased microglial activation in both symptomatic and presymptomatic HD gene carriers and that the degree of microglial activation in the striatum correlates with the severity of striatal dopamine D2 receptor dysfunction measured with (11)C-raclopride PET. Our findings indicate that microglial activation is an early process in the HD pathology, occurring before the onset of symptoms. The close spatial and temporal relationship between microglial activation and neuronal dysfunction lends further support to the pathogenic link between the two processes in HD. Further longitudinal studies are needed to fully elucidate this link. PMID- 17352939 TI - Change in MRI striatal volumes as a biomarker in preclinical Huntington's disease. AB - This article discusses the need for biomarkers and surrogate endpoints for future clinical trials in individuals at risk for Huntington's disease. Definitions and criteria are presented for biomarkers and surrogate endpoints, and data are presented suggesting that striatal volumes, as measured on MRI scans, meet the criteria for a biomarker. Biomarkers can be used in lieu of clinical endpoints in treatment trials if there is evidence that treatment affects the biomarker in a way that is predictive of endpoint status. Because there are currently no effective treatments for Huntington's disease, it is not yet possible to validate whether change in MRI striatal volumes can serve as an effective surrogate endpoint. It is recommended that future clinical trials be designed using MRI striatal volumes to "screen" potential treatments. Those treatments that reduce the rate of striatal atrophy can then be tested with delay of symptom onset as the clinical endpoint. This strategy is essential if efficient and cost-effective clinical trials are to be conducted in the preclinical stage of Huntington's disease. PMID- 17352940 TI - Ethyl-EPA in Huntington disease: potentially relevant mechanism of action. AB - The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n-3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing. PMID- 17352941 TI - Predictive testing for Huntington's disease. AB - Worldwide, predictive testing for Huntington's disease has become an accepted clinical application that has allowed many individuals from HD-families to proceed with their life without the uncertainty of being at risk. International guidelines have extensively contributed to establishing counselling programmes of high quality, and have served as a model for other genetic disorders. Psychological follow-up studies have increased the insight into the far-reaching impact of test results for all individuals involved. Although the guidelines have served as a useful frame of reference, clinical experience has shown the importance of a case-by-case approach to do justice to the specific needs of the individual test candidate. Issues such as ambiguous test results, lack of awareness in a test candidate of early signs of the disease, non-compliance to the test protocol, or the test candidate's need for information on the relationship between age at onset and CAG-repeat require careful consideration. Receiving a test result is only one of the transition points in the life of an individual at risk; such result needs to be valued from a life-cycle perspective. PMID- 17352942 TI - Can directed activity improve mobility in Huntington's disease? AB - Huntington's disease is an inherited disorder of the CNS that results in progressive deterioration of mobility and cognition and also affects behaviour. There are no disease-modifying interventions available to date, although there has been considerable progress in research directed at understanding the pathological basis of the disease with a view to identifying potential treatments. It is however important not to overlook currently available treatment strategies, including rehabilitation approaches. There has been little work to date to explore the potential of such approaches and here we highlight the need for more systematic studies in this area as well as the need for good objective assessment tools and the potential role that rehabilitation and training may have in the application of novel treatment options. PMID- 17352943 TI - Comprehensive care in Huntington's disease: a physician's perspective. AB - Huntington's disease is a slowly progressive neurodegenerative disorder with wide ranging effects on affected individuals and their families. Until a cure is found for the disease, patients and their families will continue to need care over years, even generations. The ideal care for HD is provided by a team, led by a physician, with input from rehabilitation therapists, nurses, psychologists, genetic counselors, social workers, and other health care providers. The goals of care are to maximize the quality of life at all points through the course of the disease, in part by anticipating problems that are likely to arise at the next stage of the illness. We describe below an approach to comprehensive care, and introduce the concept of the "Huntington disease molecule", in which the patient, in the center, is surrounded by a shell of immediate and extended family members, with bonds extended in multiple directions to provider who can give appropriate medical care, education, crisis management, research opportunities, address family issues, maximize function, and prepare for the future. PMID- 17352944 TI - Late stage care in Huntington's disease. AB - Huntington's disease (HD) is a relentlessly progressive neurodegenerative disease, which is presently incurable. Despite the hope for future therapies that exists for the families, they meantime are aware that there is little that their clinicians can do to delay either onset or progression of the disease. There are unique issues to address in a disorder where patients are aware in advance that their ability to communicate, as well as their cognitive capacity, will become impaired. Most affected individuals have experience of the disease in its late stages because of their parent's and other family member's illness. Many have their own ideas and anxieties about how their own care ought to proceed. There are no published guidelines for management of this stage of disease, although all clinicians involved in the care of HD will have their own experiences to share. This paper describes one method for such management, which includes discussion about placement for care advance directives for feeding and treatment. PMID- 17352945 TI - Benign epilepsy of childhood with rolandic spikes: typical and atypical variants. AB - Clinical course and outcome were compared for 126 children with typical and atypical features of benign epilepsy of childhood with rolandic spikes (BECRS). A retrospective case series design was used, in the setting of a tertiary-care pediatric hospital. The subjects were subdivided into two groups, based on clinical presentation. Group A comprised children with typical features of BECRS (n = 66; 52%) and Group B, those with atypical features (n = 60; 48%). Patients' charts were reviewed for demographic data, family history, comorbid conditions, atypical clinical features, anti-epileptic drugs, and outcome data. Comorbid disorders (e.g., attention deficit hyperactivity disorder, behavioral problems) were slightly more frequent in the atypical group. Overall, there was no difference between the time to become seizure free between the groups: by two years, 41 of 66 in Group A (62%) and 44 of 60 in Group B (71%) were controlled on medication and seizure free. Twenty of the 126 children (16%) required trial of a second anti-epileptic drug: 7 in Group A and 13 in Group B. Resolution of the epilepsy occurred in about the same length of time in both groups (but at different ages, consistent with different age of onset). Both groups had similar long-term outcome. PMID- 17352946 TI - Prevalence of headache and its association with sleep disorders in children. AB - An association between headache and sleep disturbances has been reported in previous studies, but there is a lack of research examining this relationship in a community sample of children in order to reveal the magnitude of the problem. Among 32 District Educational Directorates in Istanbul, nine school districts and within each district eight schools were randomly selected. A questionnaire consisting of sociodemographic variables and evaluating headache and sleep disturbances was sent to students' homes to be completed by their parents. The prevalence of headache was 31.4% (95% confidence interval: 29.5-33.4%). Migraine prevalence was 3.3%, whereas nonmigraine headache prevalence was 28.1%. The prevalence of headache was similar between males and females (29.6% vs 33.3%, P > 0.05). The frequency of headache increased with age for both sexes. Snoring, parasomnias, sweating during sleep, and daytime sleepiness were more common among children with migraine compared with nonmigraine and no headache groups. Headaches are common among schoolchildren. Because children with migraine headaches have a high prevalence of sleep disturbances, they should always be evaluated for the presence of sleep problems. PMID- 17352947 TI - Children with autism: effect of iron supplementation on sleep and ferritin. AB - To determine if there is a relationship between low serum ferritin and sleep disturbance in children with autism spectrum disorder, an 8-week open-label treatment trial with oral iron supplementation was conducted as a pilot study. At baseline and posttreatment visits, parents completed a Sleep Disturbance Scale for Children and a Food Record. Blood samples were obtained. Thirty-three children completed the study. Seventy-seven percent had restless sleep at baseline, which improved significantly with iron therapy, suggesting a relationship between sleep disturbance and iron deficiency in children with autism spectrum disorder. Sixty-nine percent of preschoolers and 35% of school aged children had insufficient dietary iron intake. Mean ferritin increased significantly (16 microg/L to 29 microg/L), as did mean corpuscular volume and hemoglobin, suggesting that low ferritin in this patient group resulted from insufficient iron intake. Similar prevalence of low ferritin at school age as preschool age indicates that children with autism spectrum disorder require ongoing screening for iron deficiency. PMID- 17352948 TI - Neurologic and cardiac findings in children with Sydenham chorea. AB - This study investigated the association between cardiac and neurologic findings and the long-term prognosis in Sydenham chorea. A retrospective, descriptive study was conducted with 40 patients between 1991 and 2004. Their age, gender, clinical findings, severity of disease, presence of carditis, and neurological findings were evaluated. Patients were predominantly female (70%), and the mean age was 11.3 +/- 2.5 years. The mean duration of chorea was 5.3 +/- 3.1 months (range, 1-12 months). Chorea was mild in 30 patients, moderate in 9, and severe in 1. Carditis was confirmed by echocardiography in 28 cases (70%); the most frequently involved valve was the mitral (35%). Duration of chorea in patients with carditis did not differ significantly from that in patients without carditis. Mean follow-up time was 2.6 +/- 1.5 years. Acute flaring of acute rheumatic fever did not recur in any patient taking penicillin prophylactically. No patient had persistent chorea. Although murmurs in patients with Sydenham chorea predicts carditis with high probability, the absence of murmur does not exclude it. In patients with carditis, the mitral valve is the one most frequently involved. PMID- 17352949 TI - Increased prevalence of silent celiac disease among Greek epileptic children. AB - Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Many reports mention the association between epilepsy and celiac disease and the occasional presence of occipital corticosubcortical calcifications. We investigated 255 children with idiopathic epilepsy. Evaluation included use of routine, easily obtainable studies. Patients were screened for immunoglobulin A (IgA), immunoglobulin G (IgG) antigliadin antibodies and immunoglobulin A antitissue transglutaminase antibodies. Moreover, presence of IgA antiendomysial and antireticulin antibodies was screened. Patients with positive IgA antigliadin antibodies underwent a small intestinal biopsy. Controls consisted of 280 healthy children. Intestinal histopathologic changes, positive IgA antigliadin antibodies or IgG antigliadin antibodies, antireticulin antibodies, and antitissue transglutaminase IgA antibodies were found in five epileptic children but not in control subjects (P = 0.0241). Intracranial calcifications were not found in epileptic children with celiac disease. The findings indicate that prevalence of silent celiac disease is increased among children with idiopathic epilepsy; the type of epilepsy does not appear to play a role. Serum antitissue transglutaminase IgA antibodies could be a good marker for celiac disease screening. Occipital corticosubcortical calcifications are rarer in children with celiac disease and epilepsy. PMID- 17352950 TI - Altered nestin expression in the cerebrum with periventricular leukomalacia. AB - Nestin is a cytoskeletal protein expressed by neural stem cells, and by immature neurons and glial cells. In an effort to explore the potential of the infant brain for repair and plasticity, we immunohistochemically studied nestin expression in the human cerebral cortex of control subjects and of patients with periventricular leukomalacia. During normal development, nestin immunoreactivity of the cortical gray and white matter was detectable throughout the fetal period, and disappeared around birth. In brain with periventricular leukomalacia, nestin expression was altered in a time- and space-dependent manner. In the cortical gray matter, neuronal immunoreactivity was often reduced in the subacute stage, but was increased in chronic and remote stages. In the white matter near a lesion of periventricular leukomalacia, glial immunoreactivity was increased in all stages. In many cases, neurons and axons far from a lesion also showed an altered expression of nestin. These findings indicate that in brain with periventricular leukomalacia, neurons and glial cells may recapitulate nestin expression in response to ischemic brain injury, suggesting functional relevance in repair and plasticity. PMID- 17352951 TI - Objective tinnitus due to essential palatal tremor in a 5-year-old. AB - A healthy 5-year-old male reported a clicking sound in both ears. Neurologic examination was normal except for an audible clicking noise that could be heard when within 10 cm of either ear and bilateral rapid rhythmic movements of the soft palate. All tests were normal including magnetic resonance imaging brain scan. One year after onset, his objective tinnitus and palatal tremor were no longer present. PMID- 17352952 TI - Recurrent spontaneous spinal epidural hematoma in a child: first case report. AB - Spontaneous spinal epidural hematomas are a rare cause of spinal cord compression. These are typically isolated events. Recurrent spontaneous spinal epidural hematomas have been reported only in two instances in adults. There have been no reports of recurrent spontaneous spinal epidural hematomas involving a child. This report details the case of a 10-year-old female with a recurrent spontaneous spinal epidural hematomas who presented with two episodes of transient lower extremity paralysis, 2 months apart, followed by a third episode a year later which resulted in permanent paralysis. PMID- 17352953 TI - Seizure associated with total parenteral nutrition-related hypermanganesemia. AB - The trace element manganese is usually supplied when total parenteral nutrition is used. However, long-term parenteral administration of manganese, which bypasses the normal regulatory mechanism, may cause hypermanganesemia. Manganese poisoning presents clinically with parkinsonian-like symptoms and psychological changes. Seizures are a rare presentation of this disease. This report describes a 10-year-old female who had received total parenteral nutrition for 3 months because of short bowel syndrome, and presented with tonic-clonic seizure, decreased level of consciousness, and fever. The serum electrolytes, glucose and the cerebrospinal fluid examination were normal. The blood culture grew Pantoea agglomerans. The brain magnetic resonance imaging disclosed no evidence of central nervous system infection. However, symmetric high-intensity signal on T1 weighted images was documented in the basal ganglia, especially in the globus pallidus. Her whole blood manganese level was 3.7 microg/dL, which was significantly higher than the normal range (0.4-1.4 microg/dL). Diagnosis of hypermanganesemia related to total parenteral nutrition was made. PMID- 17352954 TI - Trauma-induced dystonia and camptocormia in a child. AB - A 14-year-old male sustained neck trauma during a fight at school. Torticollis developed immediately afterwards, followed by axial dystonia and camptocormia. Thorough evaluation for etiology or background disease, including psychiatric examination, was negative except for the recent trauma. Antidystonia medications, administered after significant worsening of the symptoms, led to improvement. Dystonia and camptocormia resulting from trauma are rare presentations in childhood and adolescence. PMID- 17352955 TI - JC virus granule cell neuronopathy in a child with CD40 ligand deficiency. AB - JC virus infection of the brain typically causes progressive multifocal leukoencephalopathy, a demyelinating disease that rarely involves gray matter. This report presents a case of cerebellar degeneration associated with JC virus infection in a male with CD40 ligand deficiency resulting in hyperimmunoglobulin M type 1. This patient exhibited a progressive cerebellar ataxia with progressive atrophy of the cerebellar cortex in association with the presence of JC virus in the spinal fluid. JC virus infection should be considered in the differential diagnosis of ataxia in children with inherited immunodeficiencies. PMID- 17352956 TI - Magnetoencephalographic findings of Panayiotopoulos syndrome with frontal epileptic discharges. AB - We previously reported the results of a magnetoencephalographic study in patients with Panayiotopoulos syndrome manifesting occipital epileptic discharges, in which the equivalent current dipoles of spike discharges were clustered alongside the major cortical sulci, such as parieto-occipital and calcarine. This report is the result of a magnetoencephalographic study of three patients with Panayiotopoulos syndrome exhibiting equivalent current dipoles clustering in the frontal area. Patient 1, a 13-year-old male, exhibited clustering equivalent current dipoles alongside right inferior frontal sulcus, but the orientations were irregular. Patient 2 is an 11-year-old younger brother of Patient 1, whose magnetoencephalograph revealed equivalent current dipoles clustering alongside right prefrontal sulcus and regular orientations. Patient 3 is a 10-year-old female who had equivalent current dipoles clustering alongside right superior frontal sulcus and extremely regular orientations. The locations of clustering equivalent current dipoles of frontal spike discharges were not restricted to one specific frontal sulcus but were present in various locations over the convexity of the prefrontal area. In conclusion, these findings suggest that it is inappropriate to classify Panayiotopoulos syndrome as occipital epilepsy. In addition, the result of this study, that frontal spike discharges seem to occur in relatively older patients, may suggest a correlation between brain maturation and spike occurrence. PMID- 17352957 TI - Generalized nonconvulsive status epilepticus in symptomatic partial epilepsy. AB - A 6-year-old male with cortical dysplasia who developed secondarily generalized nonconvulsive status epilepticus is reported. He had partial epilepsy since the age of 10 months. On electroencephalography, almost continuous left frontocentral/anterior temporal spikes were observed at 3 years of age, which lasted until 6 years of age, when he developed nonconvulsive status epilepticus. Nonconvulsive status epilepticus lasted for more than 7 days. Electroencephalography during nonconvulsive status epilepticus documented almost continuous generalized polyspike-wave complexes suggestive of generalized nonconvulsive status epilepticus. On magnetic resonance imaging, abnormal gyration was observed in the left frontal lobe. Histopathologic analysis of the resected left frontal lobe revealed cortical dysplasia. The present case demonstrates that continuous focal epileptiform discharges caused by cortical dysplasia in the frontal lobe can develop into secondarily generalized nonconvulsive status epilepticus. PMID- 17352958 TI - Abnormal white matter in a neurologically intact child with incontinentia pigmenti. AB - Incontinentia pigmenti is an X-linked neurocutaneous disorder which is often lethal in males. Ectodermal tissues are involved, and affected females often have abnormalities of skin, teeth, hair, eyes, and the central nervous system. Central nervous system involvement ranges from none to multiple strokes, seizures, and mental retardation. Deletions in the nuclear factor kappa beta essential modulator gene at Xq28 are present in 70-80% of patients with incontinentia pigmenti. White matter abnormalities have been reported in females with significant neurologic involvement. This report describes a neurologically intact child with deletion positive incontinentia pigmenti with significant white matter involvement, broadening the scope of this finding in incontinentia pigmenti. PMID- 17352959 TI - Suspected herpes encephalitis and opercular syndrome in childhood. AB - Herpes simplex encephalitis is the most common form of sporadic viral encephalitis. It may occur at any age, giving rise to a syndrome with a high morbidity and mortality. Its presentation may be atypical, and the initial complementary investigations nonspecific, making early diagnosis difficult and thus worsening its prognosis. This report describes four infants with herpes encephalitis presenting with an opercular syndrome that left significant sequelae after the acute episode. The opercular syndrome is characterized clinically by a disturbance of voluntary control of the facio-linguo-glosso-pharyngeal muscles, affecting speech and swallowing. Recognition of the opercular syndrome as a form of presentation of herpes encephalitis enables early diagnosis to be made in these patients, with the rapid initiation of treatment with acyclovir, improving the clinical course. PMID- 17352960 TI - Has the first implementation phase of the Community Nutrition Project in urban Senegal had an impact? AB - OBJECTIVE: We evaluated the impact of the Community Nutrition Project (CNP) of Senegal, West Africa on the population. In poor urban districts, the CNP provided underweight 6- to 35-mo-old children with growth monitoring/promotion and food supplementation, and education for mothers for a period of 6 mo. METHODS: A before/after intervention and intervention zone (IZ)/control zone (CZ) design was used to assess whether CNP had an impact 18 mo after it began in Diourbel. Exhaustive samples included children 6-35 mo old in the CZ (n = 895 before and 917 after) and IZ (n = 912 and 759). The impact was assessed by the differential effect of the zone on changes in underweight, wasting, and stunting defined by the threshold of -2 or -3 z scores. RESULTS: The decrease in wasting was higher in the CZ (from 13.7% to 8.6% versus 11.3% to 10.8%, P = 0.042). Changes in stunting did not differ between zones (18.8% to 14.5% versus 15.1% to 14.7%, P = 0.21). However, in the IZ, severe wasting, stunting, and underweight disappeared in children 6-11 mo of age. In the CZ, the socioeconomic data and some outcomes in children reflected a favorable context independent of the CNP. CONCLUSION: Despite a globally satisfactory decrease in malnutrition in the IZ, no impact was demonstrated because the same or an even larger decrease was observed in the CZ, highlighting the importance of relying on a quasi-experimental design. This may be explained in part by weaknesses in the process, which probably interfered with a potential impact, and by the high degree of population mobility, which could have interfered with efficiency assessed on a geographic scale. PMID- 17352961 TI - Oral intake of Lactobacillus fermentum CECT5716 enhances the effects of influenza vaccination. AB - OBJECTIVE: We studied the coadjuvant capability of oral consumption of the breast milk-isolated strain Lactobacillus fermentum (CECT5716) for an anti-influenza vaccine. METHODS: A randomized, double-blinded, placebo-controlled human clinical trial including 50 volunteers (31 male and 19 female) was performed to address the immunologic effects of an intramuscular anti-influenza vaccine in adults (33.0 +/- 7.7 y old). Fifty percent of volunteers received an oral daily dose of methylcellulose (placebo) or probiotic bacteria (1 x 10(10) colony-forming units/d) 2 wk before vaccination and 2 wk after vaccination. RESULTS: Two weeks after vaccination there was an increase in the proportion of natural killer cells in the probiotic group but not in the placebo group. The vaccination induced an increase in T-helper type 1 cytokine concentrations and in T-helper and T cytotoxic proportions in both groups; however, the probiotic group showed a significant higher induction in some of these parameters. Regarding the humoral effects, induction of antibody response in the placebo group could not be detected. In the case of the probiotic group, a significant increase in antigen specific immunoglobulin A was detected. Although an increase in total immunoglobulin M was observed, changes in anti-influenza antigen specific immunoglobulin M were not observed. The incidence of an influenza-like illness during 5 mo after vaccination (October to February) was lower in the group consuming the probiotic bacteria. CONCLUSION: Oral administration of the strain L. fermentum CECT5716 potentates the immunologic response of an anti-influenza vaccine and may provide enhanced systemic protection from infection by increasing the T-helper type 1 response and virus-neutralizing antibodies. PMID- 17352962 TI - Watermelon consumption increases plasma arginine concentrations in adults. AB - OBJECTIVE: Watermelon is a rich source of citrulline, an amino acid that can be metabolized to arginine, a conditionally essential amino acid for humans. Arginine is the nitrogenous substrate used in the synthesis of nitric oxide and plays an essential role in cardiovascular and immune functions. No detailed studies have been conducted to evaluate plasma arginine response in humans after long-term feeding of citrulline from natural plant sources. This study investigated if watermelon juice consumption increases fasting concentrations of plasma arginine, ornithine, and citrulline in healthy adult humans. METHODS: Subjects (n = 12-23/treatment) consumed a controlled diet and 0 (control), 780, or 1560 g of watermelon juice per day for 3 wk in a crossover design. The treatments provided 1 and 2 g of citrulline per day. Treatment periods were preceded by washout periods of 2 to 4 wk. RESULTS: Compared with the baseline, fasting plasma arginine concentrations increased 12% after 3 wk of the lower-dose watermelon treatment; arginine and ornithine concentrations increased 22% and 18%, respectively, after 3 wk of the higher-dose watermelon treatment. Fasting citrulline concentrations did not increase relative to the control but remained stable throughout the study. CONCLUSION: The increased fasting plasma concentrations of arginine and ornithine and stable concentrations of plasma citrulline in response to watermelon juice consumption indicated that the citrulline from this plant origin was effectively converted into arginine. These results demonstrate that plasma concentration of arginine can be increased through intake of citrulline from watermelon. PMID- 17352963 TI - Postprandial leucine deficiency failed to alter muscle protein synthesis in growing and adult rats. AB - OBJECTIVE: This study examined the effect of a specific acute postprandial leucine deficiency on skeletal muscle protein synthesis in growing and adult rats. Because the anabolic action of dietary leucine supplementation is controversial, except during aging, we hypothesized that the maximum leucine effect might be already achieved for a normal postprandial rise of leucine. Preventing this rise during the 1- to 3-h period after feeding may reveal the leucine regulation. METHODS: On the day of the experiment, rats were fasted (postabsorptive, PA group) or fed for 1 h a control meal (postprandial, control, PP group) or a leucine-poor meal (postprandial, PP-Leu group). Muscle protein synthesis was assessed in vivo, over the 1- to 3-h period after meal distribution, using the flooding dose method (L-1-(13)C phenylalanine). RESULTS: As expected, the postprandial increase in plasma free leucine was specifically abolished after feeding the leucine-poor meal, whereas all the other plasma free amino acids were roughly at normal postprandial levels. Plasma insulin increased after feeding in young rats but was constant in adult rats. Plasma insulin was similar whatever dietary leucine levels. Rates of muscle protein synthesis were stimulated by feeding in gastrocnemius and soleus muscles from young rats but only in gastrocnemius muscles from adult rats. The PP-Leu group did not differ from the control PP group regarding muscle protein synthesis. CONCLUSION: The rise in plasma free leucine is not required for the stimulation of muscle protein synthesis during the 1- to 3-h period after feeding young and adult rats, as previously observed in old rats. PMID- 17352964 TI - Persistent anemia after Roux-en-Y gastric bypass. AB - OBJECTIVE: We report the case of a 42-y-old morbidly obese woman who presented persistent anemia as result of Roux-en-Y gastric bypass. METHODS: The surgical procedure conducted in 1999 consisted of horizontal gastroplasty with truncular vagotomy, Roux-en-Y gastrojejunal anastomosis with an alimentary limb of 60 cm, and cholecystectomy. In 2000 a second surgery (subtotal gastrectomy, i.e., 90%, with a 50-mL gastric pouch) was performed because of failed gastroplasty. Anemia was detected approximately 1 y after the second surgery. This condition worsened significantly after an abdominal lipectomy performed in 2001. Since then, different oral iron compounds were used for treatment, but with unsatisfactory results. The subject was anemic for 4 y. RESULTS: The condition was corrected only after intravenous iron administration. Iron absorptions from 3 mg of iron as ferrous ascorbate and from a standardized diet that also contained 3 mg of iron were 48.4% and 39.9%, respectively. CONCLUSION: Iron absorption tests provided evidence that the reduction of intestinal iron absorption capacity was the most probable cause of the persistent anemia. PMID- 17352965 TI - Herbal research: the good, the bad and the worrying. PMID- 17352966 TI - The effects of P6 acupressure in the prophylaxis of chemotherapy-related nausea and vomiting in breast cancer patients. AB - BACKGROUND: Nausea, and to a lesser extend vomiting, remain significant clinical problems after the administration of chemotherapy, with up to 60% of patients reporting nausea despite use of antiemetics. Combining antiemetics with other non pharmacological treatments may prove more effective in decreasing nausea than antiemetics alone. Hence, the aim of the current study was to evaluate the effectiveness of using acupressure in Pericardium 6 (Neiguan) acu-point in managing chemotherapy-induced nausea and vomiting. METHODS: This was a randomised controlled trial. Acupressure was applied using wristbands (Sea-Band) which patients in the experimental group had to wear for the 5 days following the chemotherapy administration. Assessments of nausea, retching and vomiting were obtained from all patients daily for 5 days. Thirty-six patients completed the study from two centres in the UK, with 19 patients allocated to the control arm and 17 to the experimental arm. RESULTS: It was found that nausea and retching experience, and nausea, vomiting and retching occurrence and distress were all significantly lower in the experimental group compared to the control group (P<0.05). The only exception was with the vomiting experience, which was close to significance (P=0.06). DISCUSSION: Results highlight the important role of safe and convenient non-pharmacological complementary therapies, such as acupressure, in the management of the complex symptoms of chemotherapy-related nausea and vomiting. PMID- 17352967 TI - An examination of the prescription and dispensing of medicines by Western herbal therapists: a national survey in Australia. AB - OBJECTIVE: To describe the patterns of prescription and dispensing of herbal medicines employed by Western herbal practitioners in Australia. DESIGN: A national postal survey sent to all full members of the National Herbalist Association of Australia (NHAA). SETTING: Nationwide clinics of professional herbal practitioners in Australia. MAIN OUTCOME MEASURES: Measures of medicinal use were collected including aspects of prescription, formulation, dispensing and preparation forms of medicines used. The practitioners were asked if they dispensed their own medicines, about the form of herbal preparations used, aspects of formulation and dosages. RESULTS: The predominant prescription by most Western herbal practitioners in Australia is individualised herbal formulae rather than the use of single herbs. Traditional preparations of herbals such as teas and powders are used but liquid herbal extracts are most commonly dispensed. These liquid medicines are in the form of highly concentrated fluid extracts in ratios of 1:1 or 1:2, herb material to liquid. Pre-formulated tablets or capsules made by herbal manufacturers are being incorporated into modern practice but most prescriptions are individualised liquid formulae prepared and dispensed, from the clinic dispensary, after patient consultation. In addition to internal prescriptions, topical creams, pessaries, douches, gargles, eyebaths and poultices or washes are still incorporated into treatments. Although there is variation in used dosage ranges, the predominant system is that of pharmacologically active doses of highly concentrated fluid extracts. CONCLUSION: The professional prescription of Western herbal medicines is different to commercial usage. As opposed to pre-formulated tablets, or use of single herbals, the vast majority of Western herbalists in Australia construct individualised herbal formulations for their patients after consultation. The preferred form of administration of these prescriptions is as highly concentrated liquid herbal extracts in pharmacologically active doses. PMID- 17352968 TI - Use of complementary and alternative medicine and prayer among a national sample of cancer survivors compared to other populations without cancer. AB - OBJECTIVES: Extensive use of complementary and alternative medicine (CAM) among cancer survivors has been described in literature, but the rate has not previously been compared to other groups in a true population sample. METHODS: We performed a cross-sectional study using data from the 2002 National Health Interview Survey to determine the prevalence of CAM and prayer for health (PFH) use among cancer survivors and compared the rates of such use among cancer survivors with the US general and other chronic diseased populations while controlling for key socio-demographic factors. RESULTS: Among 31,044 adult survey respondents, 1904 had a prior cancer diagnosis, of whom 40% reported CAM and 62% reported PFH use during the year before the survey. The top three CAM modalities were herbs (20%), deep breathing (14%) and meditation (9%). Controlling for other factors, cancer survivors used more CAM than the general population (adjusted odds ratio [OR] 1.36, 95% confidence interval [CI] 1.20-1.53), but similar to those with chronic symptomatic illness (p=0.5). Cancer survivors used PFH more than the general population (OR 1.87, 95% CI 1.66-2.10) and all other groups (p<0.001). The greater CAM and PFH use by cancer survivors was seen in both recent and distant diagnoses (>10 years). CONCLUSION: A previous cancer diagnosis is associated with a modest increase in CAM use compared with the general population but similar to other chronic symptomatic illnesses; however, cancer survivors are more likely to pray for health than all other populations. Exploring CAM and prayer use in clinical settings may help clinicians better understand the needs of their patients. PMID- 17352969 TI - Patterns of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease: perceived stress is a potential indicator for CAM use. AB - INTRODUCTION: The reasons for using complementary and alternative medicine (CAM) and the perception of stress in a group of patients with inflammatory bowel disease (IBD) who are actively interested in CAM were compared with those of a randomly selected group of IBD patients (controls). METHODS: Participants in a national lay workshop on CAM of the German Crohn's and Ulcerative Colitis Association (DCCV) (the study group) and a representative sample of the approximately 16,000 members and associates of the DCCV (the control group) were asked to complete a self-administered questionnaire that covered socio demographic data, past medical history, stress perception, current conventional treatment, and interest in, and usage of, CAM. RESULTS: One-hundred and twelve (80%) of the approximately 140 participants of the lay workshop and 684 (68.8%) of the 994 IBD patients in the control group completed and returned the questionnaires. The duration of illness, taken as the time since diagnosis, was shorter for the participants of the lay workshop than for the control group (p=0.0035), and fewer workshop patients stated that their disease was currently "in remission" (p=0.0377). The two groups did not differ significantly in their experiences with CAM use. Among personal reasons given for CAM use, the "lack of success of conventional therapy" (p=0.014), the wish "to take a holistic therapeutic approach" (p=0.0008), and "a different point of view from that of my physician about the cause of, and treatment options for, IBD" (p=0.038) were chosen more often in the group of workshop participants than in the control patients. A total of 92% of the workshop patients perceived stress as having a negative effect on their IBD; this is a significantly greater percentage than in the control group (70.5%; p=0.0001). CONCLUSIONS: A group of IBD patients with an active interest in CAM showed distinct differences from a randomly selected group of IBD patients in their reasons for using CAM, particularly in their wish to take a holistic therapeutic approach. Patients who think that stress has a negative effect on their IBD appear to be more likely to use CAM. PMID- 17352970 TI - Measure Yourself Concerns and Wellbeing (MYCaW): an individualised questionnaire for evaluating outcome in cancer support care that includes complementary therapies. AB - BACKGROUND AND AIM: Descriptive and experimental evaluations of cancer support services require an outcome questionnaire that is valid, responsive to change, feasible and interpretable. This paper describes the development of such a tool. DEVELOPMENT OF THE QUESTIONNAIRE: A validated individualised measure MYMOP was adapted and piloted in two centres, and a multidisciplinary research team used this experience to develop the new questionnaire, Measure Yourself Concerns and Wellbeing (MYCaW). MYCaW requires participants to nominate one or two concerns and, using a seven-point scale, to score these concerns and their general feeling of wellbeing. The follow-up questionnaire also includes the open question 'Reflecting on your time with this Centre, what were the most important aspects for you?' INVESTIGATING VALIDITY: During 2003 the two centres administered MYCaW to all new patients, before and after a course of treatment. Patients nominated concerns that spanned physical, emotional and psychosocial concerns. For patients completing follow-up questionnaires (n=254 at the Cavendish Centre and n=267 at the Bristol Cancer Help Centre), the mean change (S.D.) for the first concern score was 2.9 (1.63) and 1.91 (1.58) for the second concern score 2.5 (1.73)/1.77 (1.96) and for the wellbeing score 1.4 (1.8)/0.61 (1.52), respectively. The open question collected valuable extra data. DISCUSSION: MYCaW is a questionnaire that is appropriate for the service offered, acceptable to patients, practitioners and researchers, and is responsive to change. Further validation work is planned. PMID- 17352971 TI - Green tea and stroke prevention: emerging evidence. AB - BACKGROUND: Stroke is a leading cause of morbidity and mortality in many countries. Green tea is a simple and inexpensive beverage that is showing promise in the prevention of several diseases, including stroke. However, epidemiological studies examining the preventive effects of tea on stroke have generated inconsistent results. OBJECTIVE: To review the emerging evidence for green tea in stroke prevention. METHODS: Published articles were located by searching the PubMed, ProQuest, CINAHL and other databases, using the keywords 'tea' and 'stroke' with no restriction on publication date. Reference lists of identified articles were also searched for relevant publications. RESULTS: Two published epidemiological studies on green tea reported positive findings. A large number of studies have also proposed biological mechanisms by which tea or tea components may reduce the stroke risk. Additional studies are required from a variety of populations, assessing duration and different types of tea consumption on subtypes of stroke to provide further evidence. CONCLUSION: Green tea is a safe and cheap beverage. Its consumption should be encouraged because it could potentially serve as a practical method for stroke prevention. PMID- 17352972 TI - Traditional Chinese medicine--what are we investigating? The case of menopause. AB - CAM researchers commonly treat traditional medicines as unchanging systems. This article questions the validity of this approach by examining the treatment of menopausal syndrome by traditional Chinese medicine (TCM). Such treatment strategies were invented in 1964 and betray a strong influence of biomedical thinking. While they determine TCM treatment of menopausal syndrome in the West, physicians in China and Japan use many other treatment strategies from within the wider Chinese medical tradition in clinical practice. Cultural variability in the manifestation of menopausal syndrome furthermore questions the usefulness of simply importing treatment strategies from China to the West. This leads me to conclude that Chinese medicine as such can never be evaluated by means of clinical research. What we can do is use Chinese medicine as a resource for thinking about illness, and for formulating clinical interventions that may then be assessed using methods of evidence based research. PMID- 17352973 TI - Difficult behaviors in long-term care patients with dementia. AB - Difficult behaviors are relatively common challenges that can occur throughout the natural progression of dementia, but are particularly common in the mid to late stages of disease. These behaviors can be challenging to manage in nursing and assisted care facilities, and can cause distress to the caregivers and to the patients themselves. Our ability to manage these symptoms can have a profound effect on the patient's quality of life. This article reviews the appropriate assessment of behavioral and psychological symptoms of dementia (BPSD) and the literature supporting various nonpharmacologic and pharmacologic treatments. Nonpharmacologic approaches should be the initial focus for treatment of most BPSD, but should these prove inadequate, a variety of medications are available with varying degrees of clinical research to support their use in ameliorating BPSD. PMID- 17352975 TI - The new F-tag 314: prevention and management of pressure ulcers. PMID- 17352977 TI - Defining and measuring quality outcomes in long-term care. AB - The US health care industry increasingly agrees that sharing information about quality of care is necessary to stimulate providers' efforts to improve the quality of health care. The availability of mandated, uniform clinical data in all nursing homes and home health agencies has facilitated the rapid adoption of public reporting of comparative quality data. This paper examines the conceptual and technical challenges underlying the application of information about long term care provider quality to judge and compare the quality of care provided by nursing homes and home health agencies. In general, the impetus to apply the emerging set of quality "tools" based on mandated clinical assessments may have outstripped the evidence for their valid application in selecting top providers or for rewarding their superior performance. PMID- 17352979 TI - A quality improvement study on calcium and vitamin D supplementation in long-term care. AB - OBJECTIVES: The objectives of this study were to evaluate the impact of a quality improvement (QI) study on improving calcium and vitamin D supplementation in a long-term care setting. DESIGN: Retrospective chart review. SETTING: An academic long-term care facility that specializes in dementia care in St Louis, MO. PARTICIPANTS: Participants consisted of 83 long-term care residents. INTERVENTION: The quality improvement team created an educational letter that was signed by the medical director and sent to the facilities' primary care physicians. This letter provided clinicians with the rationale and method to achieve adequate calcium supplementation, assess vitamin D status, and provide adequate vitamin D supplementation in our long-term care setting. Following the letter, the facility pharmacist reviewed the orders during monthly medication reviews and faxed requests to the primary care physicians for appropriate supplements or laboratory tests when necessary. MEASUREMENTS: We reviewed the charts for the presence of calcium supplementation orders, vitamin D levels, and vitamin D supplementation before and after our QI intervention. RESULTS: Of the 83 resident charts that were reviewed, only 37 (44.6%) had calcium supplementation, 19 (22.8%) had assessment of their vitamin D status, and 29 (34.9%) had ongoing vitamin D supplementation prior to implementation of the study. After the QI intervention, calcium supplementation was present in 66 residents (79.5%), vitamin D status had been assessed in 61 residents (73.4%), and vitamin D supplementation had been initiated in 65 residents (78.3%). These changes were statistically significant (P < .05). CONCLUSION: A quality improvement project that used an educational letter from the medical director combined with a medication and laboratory review by the pharmacist was able to increase the number of residents in our long-term care setting with calcium supplementation, increase the number of residents who had vitamin D status assessed, identify many residents with low vitamin D levels, and increase supplementation of vitamin D when indicated. PMID- 17352981 TI - Cardiac arrests in skilled nursing facilities: continuing room for improvement? AB - OBJECTIVES: To characterize the care received by skilled nursing facility (SNF/NF) patients suffering cardiac arrest and to evaluate the outcome of SNF/NF patients experiencing cardiac arrest. DESIGN: A retrospective analysis of an existing cardiac arrest registry to characterize SNF/NF cardiac arrest patients and to compare them to community-dwelling cardiac arrest patients was performed. SETTING: The study took place in Rochester, NY, an urban city in upstate New York with approximately 220,000 residents. PARTICIPANTS: All patients for whom emergency medical services (EMS) assistance was requested via the 911 system and who were treated for cardiac arrest between January 1998 and December 2001 were included. MEASUREMENTS: Demographic characteristics such as age, gender, race; clinical characteristics and interventions such as cardiopulmonary resuscitation (CPR), defibrillation, initial cardiac rhythm, and call response interval; outcomes measures such as return of spontaneous circulation and 1-year survival were obtained. RESULTS: Forty-two (8%) of cardiac arrest patients resided in an SNF/NF. Sixteen (38%) of the events were witnessed arrests. Only 28 (67%) patients received CPR and none were defibrillated prior to EMS arrival. One (2%) patient was alive 1 year after the event, a survival rate similar to the community-dwelling population (5%). CONCLUSION: SNF/NF patients suffering cardiac arrest often did not receive CPR or defibrillation while awaiting EMS arrival. SNF/NF patients suffering cardiac arrest have a very low survival rate, similar to the community-dwelling population. The impact of not providing CPR and defibrillation on the survival rate is unclear, but needs to be evaluated prior to any decisions regarding the medical futility of resuscitating SNF/NF patients. PMID- 17352984 TI - Eliciting goals of care in a nursing home. AB - OBJECTIVES: To identify enablers and barriers facing providers and staff in initiating Goals of Care (GOC) discussions with patients in the nursing home. DESIGN: Qualitative methods, one-on-one interviews. The interviews began with eliciting the participant's definition of GOC. The open-ended questions were designed to assess recent experience and satisfaction with the participant's role in the GOC discussion. SETTING: Nursing home. PARTICIPANTS: We interviewed 23 nursing home staff and providers. MEASUREMENTS: Transcripts were qualitatively analyzed. RESULTS: Five themes emerged that were identified as barriers to discussing GOC: (1) Fear of legal ramifications; (2) Not enough education on how to have a GOC discussion; (3) Family not involved on a regular basis; (4) Time pressure; (5) Interdisciplinary team not involved. Five themes also emerged that were identified as enablers to the GOC discussion: (1) Education/experience with the GOC discussion; (2) Interdisciplinary team involved in the discussion; (3) Established trusting relationship with the patient/family/other staff; (4) Terminal diagnosis/hospice involvement; (5) Discussion occurs in-person. CONCLUSION: A major finding of these interviews is the lack of systematic attention to GOC in the nursing home setting. Since education and experience were identified as crucial to understanding GOC, more formal education and observed practice discussing GOC is needed for all staff. The outcomes of GOC discussions should be documented in the patient record and be accessible to all staff and communicated systematically to all staff. Addressing these barriers and facilitating these enablers to the GOC discussion will improve the care of nursing home patients. PMID- 17352986 TI - Barriers to the implementation of palliative care in the nursing home. PMID- 17352989 TI - The application of evidence-based principles of care in older persons (issue 1): management of osteoporosis. PMID- 17352991 TI - Physical abuse of the elderly: the medical director's response. PMID- 17352993 TI - To treat or not to treat, that is the question: proceedings of the Quebec symposium for the treatment of osteoporosis in long-term care institutions, Saint Hyacinthe, Quebec, November 5, 2004. AB - OBJECTIVES: Patients in long-term care institutions (LTCI) are especially at risk for osteoporotic fractures owing to their lack of mobility, poor nutrition, and limited sun exposure. Previous reports have shown that osteoporosis is underdiagnosed and undertreated in LTCI despite the high incidence of osteoporotic fractures in these settings. This document has been developed to assist clinicians practicing in LTCI with the diagnosis and treatment of osteoporosis in their institutionalized patients. These proceedings offer an overview of the particular characteristics of patients at LTCI. Management strategies include both nonpharmacological and pharmacological interventions for the prevention and treatment of osteoporotic fractures in very frail older subjects. PARTICIPANTS: This guide is an edited review of presentations and discussions held by specialists in osteoporosis in the elderly together with physicians and pharmacists practicing in LTCI in the province of Quebec. This symposium was held in Saint-Hyacinthe, Quebec on November 5, 2004. VALUES: The value of a given diagnostic test or treatment option was determined based on the clinical experiences and opinions of the participants and a review of the literature from an evidence-based perspective. RECOMMENDATIONS: All patients located at LTCI are at potential risk for osteoporotic fractures. Global interventions should include vitamin D, calcium, and a comprehensive exercise program. In patients who are at high risk for osteoporotic fractures or with previous fractures, pharmacological treatment should be started. VALIDATION: These recommendations were approved during the final plenary of the symposium. All the prevailing opinions were summarized and included in this article. PMID- 17352996 TI - The application of evidence-based principles of care in older persons (issue 4): pain management. PMID- 17352998 TI - Dementia assessment and management. AB - Dementia is a common yet potentially underdiagnosed illness in the long-term care setting. Targeted screening for dementia should be routine practice, as a diagnosis of dementia will have benefits to the care of the patient. Assessment of dementia should proceed in a step-wise approach and should be tailored to the needs of the individual patient. Management of dementia involves care for the cognitive changes, behavioral changes, functional changes, and emotional issues. It also involves the management of other illnesses in light of the dementia, consideration of the needs and well-being of the caregiver, and particular attention to advanced care planning. Management techniques and goals should evolve as the patient's illness progresses. This comprehensive approach to management of dementia may reduce morbidity and mortality associated with this illness. This model of care provides patients and families with needed information and resources, a clear view of prognosis, and necessary attention to quality of life issues. PMID- 17352999 TI - Anemia increases risk for falls in hospitalized older adults: an evaluation of falls in 362 hospitalized, ambulatory, long-term care, and community patients. AB - OBJECTIVE: The objective of this study was to determine if a relationship exists between the presence of anemia and the occurrence of falls during hospitalization in ambulatory older adults from long-term care and community settings. All individuals were hospitalized for acute conditions not related to a fall. PARTICIPANTS: Three hundred sixty-two hospitalized, ambulatory older (59-104 years) adults. MEASUREMENTS: Laboratory values (hemoglobin [Hb], hematocrit [Hct]), routine laboratory tests, pertinent medical history, and demographics. RESULTS: Ambulatory hospitalized patients who fell were compared to controls (no falls during hospitalization) of similar age (P = .283) and gender distribution (P = .554). Patients who fell had significantly lower Hb (P < .00005), lower Hct (P < .00005) and were more likely to be anemic (56% vs 38%, P = .001) than controls. A logistic regression model examined the effect of Hb level and anemia on falls and included the covariates of age, gender, place of residence, and race. The model described a 22% decreased risk of falls for every 1.0 g/dL increase in Hb (P < .0005) and an overall 1.9-fold increased risk of falls in anemic patients (P < .001). Patient age, gender, and place of residence were not related to the risk of falls during hospitalization. CONCLUSIONS: These findings suggest a potentially important link between anemia and the risk of falls during hospitalization in ambulatory older patients. Further studies are needed to determine if the risk of falls can be modified by correction of anemia and to determine the applicability of these findings to older adults in different settings. PMID- 17353001 TI - A qualitative study on the comfort and fit of ladies' dress shoes. AB - The perceived differences between comfortable and uncomfortable shoes and the fit preferences in the different regions of ladies' shoes were explored. Twenty Hong Kong Chinese females participated in the study. Each participant wore and rated the different aspects of their own comfortable and uncomfortable shoes. The Wilcoxon signed rank tests showed significant differences in ten perceived characteristics between the comfortable and uncomfortable shoes. Among the ten were tactile, auditory and olfactory sensations. The ten items reliably (Cronbach alpha>0.9) distinguished between comfortable and uncomfortable shoes. There were no significant differences between comfortable and uncomfortable shoes for aesthetic-related characteristics. Further analysis on the fit ratings showed a significant impact on the fit preferences in the Toe region (p<0.0001), Metatarsophalangeal (MPJ) region (p<0.0001), Arch region (p=0.002) and Ingress/egress opening (p<0.001). Knowing the preferred type of fit can help establish a specification for comfortable shoes and also brings out the criteria that a comfortable shoe does not necessarily have the same perceived fit in every region of a shoe. PMID- 17353003 TI - A novel variant of the putative demethylase gene, s-JMJD1C, is a coactivator of the AR. AB - Evidence is accumulating in support of the view that tissue-specific effects of steroid hormones depend on the recruitment of nuclear receptor comodulator proteins. The latter interact directly with the hormone receptors and modify their transcriptional effects on specific target genes. The mechanisms of comodulator influence on nuclear receptor-controlled gene transcription is only partially understood. Here, we describe the discovery of a new AR coactivator which belongs to the JmjC containing enzyme family as a novel variant of JMJD1C (jumonji domain-containing 1C). By using a fragment of the human AR (aa 325-919) as bait in a yeast two-hybrid screen, a region of the human JMJD1C gene was identified as interacting with AR. A novel splice variant s-JMJD1C was amplified by RACE, and the binding to AR was analysed by GST-pull-down and mammalian one hybrid experiments. As a nuclear-localized protein, the s-JMJD1C gene is expressed in a variety of human tissues. In the brain, this protein is present in several, but not confined to, AR-expressing neuronal populations and its abundance varies with the hormonal status in a region-specific fashion. Interestingly, the expression of s-JMJD1C is reduced in breast cancer tumors and significantly higher in normal breast tissues indicating a putative role in tumor suppression. As s-JMJD1C has putative demethylase activity, removal of methylation seems to be important for nuclear receptor-based gene regulation. PMID- 17353002 TI - Characterization of superoxide production from aldehyde oxidase: an important source of oxidants in biological tissues. AB - Aldehyde oxidase, a molybdoflavoenzyme that plays an important role in aldehyde biotransformation, requires oxygen as substrate and produces reduced oxygen species. However, little information is available regarding its importance in cellular redox stress. Therefore, studies were undertaken to characterize its superoxide and hydrogen peroxide production. Aldehyde oxidase was purified to >98% purity and exhibited a single band at approximately 290 kDa on native polyacrylamide gradient gel electrophoresis. Superoxide generation was measured and quantitated by cytochrome c reduction and EPR spin trapping with p-dimethyl aminocinnamaldehyde as reducing substrate. Prominent superoxide generation was observed with an initial rate of 295 nmol min(-1) mg(-1). Electrochemical measurements of oxygen consumption and hydrogen peroxide formation yielded values of 650 and 355 nmol min(-1) mg(-1). In view of the ubiquitous distribution of aldehydes in tissues, aldehyde oxidase can be an important basal source of superoxide that would be enhanced in disease settings where cellular aldehyde levels are increased. PMID- 17353004 TI - Binding of bovine prion protein to heparin: a fluorescence polarization study. AB - Glycosaminoglycans (GAGs) are believed to be associated with prion disease pathology and also with metabolism of the prion protein. Fluorescence polarization assay (FPA) of binding between bovine recombinant prion protein (brecPrP) and heparin labelled with AlexaFluor488 was used in model experiments to study glycosaminoglycan-prion protein interaction. Heparin binding to brecPrP was a rapid reversible event which occurred under defined conditions. The interaction of brecPrP with fluorophore-labelled heparin was inhibited by the presence of Cu(2+) ions and was sensitive to competition with heparin, heparan sulphate, and dextran. The dissociation constant of the heparin-brecPrP complex was 73.4+/-3.7 nM. Circular dichroism (CD) experiments indicated that the structure of brecPrP was less helical in the presence of heparin. PMID- 17353005 TI - Apoprotein E isoform-dependent expression and secretion of pro-inflammatory cytokines TNF-alpha and IL-6 in macrophages. AB - The anti-atherogenic properties of human apoprotein E-associated lipoproteins have been partially attributed to its anti-inflammatory properties. We studied if endogenously expressed apoprotein E (apoE) elicits isoform-dependent effects on pro-inflammatory cytokine expression and secretion. Mouse J774A.1 peritoneal macrophages without native expression of apoE were used to establish cell lines with stable expression of the three human apoE isoforms, apoE2, apoE3 and apoE4. In the presence of lipopolysaccharide (LPS), expression and secretion of TNF alpha and IL-6 in cells expressing different apoE isoforms were determined by RT PCR, immunoblotting and ELISA assays. ApoE3-expressing cells have significantly lower expression and secretion levels of the two cytokines as compared to cells with apoE2 and apoE4 expression. Such observations were accompanied with the lowest ERK1/2 activity in apoE3-expressing cells. Further study shows that the apoE isoform-dependent variations of TNF-alpha and IL-6 expression/secretion in macrophages are diminished in the presence of ERK1/2 inhibitor U0126. In conclusion, apoE elicits isoform-dependent effects on macrophage TNF-alpha and IL 6 expression as well as secretion. The ERK1/2 signaling pathways are involved in mediating such apoE isoform-dependent effects. PMID- 17353006 TI - Structure-activity relationships of flavonoid-induced cytotoxicity on human leukemia cells. AB - The aim of this study was to identify structure elements in flavonoids that are associated with enhanced cytotoxic activity. We determined the cytotoxicity (EC(50)) of 23 different flavonoids, including O-methylated and glucuronidated metabolites, on the human leukemia cell line Jurkat E6-1 by analyzing cell death triggered after 24 and 48 h. By comparing the cytotoxicity of selected molecules that differ in only one structure element, we identified several structure function relationships associated with enhanced cytotoxicity, including the presence of a 2-3 double bond, the presence of a 4-carbonyl group and ortho- compared to meta-hydroxylation in the B ring. Molecules with a 3-hydroxyl group exhibited significantly lower cytotoxicity than their non-hydroxylated counterparts. O-Methylation and glucuronidation were associated with a significant increase in cytotoxicity, suggesting that metabolites found in vivo are more active than unmodified flavonoids. We identified the solubility maximum of the tested flavonoids in culture medium and found a negative correlation between maximum solubility and cytotoxicity. The results of our study may help to identify novel flavonoid structures with optimized cytotoxic activity to be tested for anti-cancer treatment. PMID- 17353007 TI - Enhanced transaminase activity of a bifunctional L-aspartate 4-decarboxylase. AB - L-Aspartate 4-decarboxylase (Asd) catalyzes mainly the beta-decarboxylation of aspartate and also transamination with alpha-keto acids. To investigate residues that are critical in directing the reaction pathway, seven point mutations were designed based on the differences between Asd and amiontransferases in conservative amino acid residues. All mutant Asds were purified and characterized. The F204W mutant enhanced aminotransferase activity, and its ratio to beta-decarboxylase activity was 3.8-fold. Its K(m) values for aspartate and alpha-ketoglutarate were 1.3 and 0.17 mM, respectively, representing a large increase in the binding affinity with substrates. The K347R mutation did not increase transaminase activity. The D360P mutation decreased transaminase activity and was more specific in catalyzing beta-decarboxylation reaction. This is the first study that successfully increased transaminase activity in Asd via site-directed mutagenesis. The modeled protein structure reveals how the residue may involve in reaction specificity, providing insights into comprehending the molecular evolution of this bifunctional enzyme. PMID- 17353008 TI - Anti-tumor activity of N-hydroxy-7-(2-naphthylthio) heptanomide, a novel histone deacetylase inhibitor. AB - Histone deacetylase (HDAC), a key enzyme in gene expression and carcinogenesis, is considered an attractive target molecule for cancer therapy. Here, we report a new synthetic small molecule, N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), as a HDAC inhibitor with anti-tumor activity both in vitro and in vivo. The compound inhibited HDAC enzyme activity as well as proliferation of human fibrosarcoma cells (HT1080) in vitro. Treatment of cells with HNHA elicited histone hyperacetylation leading to an up-regulation of p21 transcription, cell cycle arrest, and an inhibition of HT1080 cell invasion. Moreover, HNHA effectively inhibited the growth of tumor tissue in a mouse xenograph assay in vivo. Together, these data demonstrate that this novel HDAC inhibitor could be developed as a potential anti-tumor agent targeting HDAC. PMID- 17353010 TI - Protective effect of a novel cystine C(60) derivative on hydrogen peroxide induced apoptosis in rat pheochromocytoma PC12 cells. AB - Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities, especially neural diseases. One of the effective ways to prevent the reactive oxygen species (ROS) mediated cellular injury is dietary or pharmaceutical augmentation of free radical scavengers. In the present study, we describe the synthesis and characterization of a novel cystine C(60) derivative (CFD). The compound was analyzed by FT-IR, (1)H NMR, (13)C NMR, LC-MS and elemental analysis. It contains five cystine moieties per C(60) molecule. This water-soluble amino-fullerene derivative was able to scavenge both superoxide and hydroxyl radical with biocompatibility. We investigated its potential protective effects on hydrogen peroxide-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. Cells treated with hydrogen peroxide underwent cytotoxicity and apoptotic death determined by MTT assay, flow cytometry analysis, PI/Hoechst 33342 staining and glutathione peroxidase assay. The CFD was able to reduce the accumulation of reactive oxygen species and cellular damage caused by hydrogen peroxide in PC12 cells. RF assay demonstrated that CFD could penetrate through the cell membrane and it has played its distinguished role in protecting PC12 cells against hydrogen peroxide-induced cytotoxicity. The results suggest that CFD has the potential to prevent oxidative stress-induced cell death without evident toxicity. Hence, we can hypothesize that the protective effect of CFD on hydrogen peroxide-induced apoptosis is related to its scavenger activity. PMID- 17353011 TI - Analyzing the evolution of beta-endorphin post-translational processing events: studies on reptiles. AB - In many cartilaginous fishes, most ray-finned fishes, lungfishes, and amphibians, the post-translational processing of POMC includes the monobasic cleavage of beta endorphin to yield an opioid that is eight to ten amino acids in length. The amino acid motif within the beta-endorphin sequence required for a monobasic cleavage event is -E-R-(S/G)-Q-. Mammals and birds lack this motif and as a result beta-endorphin(1-8) is a not an end-product in either group. Since both mammals and birds were derived from ancestors with reptilian origins, an analysis of beta-endorphin sequences from extant groups of reptiles should provide insights into the manner in which beta-endorphin post-translational processing mechanisms have evolved in amniotes. To this end a POMC cDNA was cloned from the pituitary of the turtle, Chrysemys scripta. The beta-endorphin sequence in this species was compared to other reptile beta-endorphin sequences (i.e., Chinese soft shell turtle and gecko) and to known bird and mammal sequences. This analysis indicated that either the loss of the arginine residue at the cleavage site (the two turtle species, chick, and human) or a substitution at the glutamine position in the consensus sequence (gecko and ostrich) would account for the loss of the monobasic cleavage reaction in that species. Since amphibians are capable of performing the beta-endorphin monobasic reaction, it would appear that the amino acid substitutions that eliminated this post-translational process event in reptilian-related tetrapods must have occurred in the ancestral amniotes. PMID- 17353012 TI - Cortisol regulates eel (Anguilla anguilla) aquaporin 3 (AQP3) mRNA expression levels in gill. AB - Previous studies in eel (Anguilla anguilla) gill have shown that the expression of the aquaporin 3 (AQP3) water and small solute channel is dramatically decreased (mRNA abundance decreased by up to 97%) when these euryhaline fish are acclimated from freshwater (FW) to seawater (SW). However, AQP3 mRNA expression levels in the intestine following SW-acclimation do not change. The SW acclimating corticosteroid hormone, cortisol has previously been shown to regulate the expression of aquaporins (particularly AQP1) in eel osmoregulatory tissues in a tissue-specific and isoform-specific fashion. AQP1 is up-regulated in intestine and oesophagus, but down-regulated in kidney, following SW acclimation in these fish. This study extends knowledge of the regulation of aquaporin expression by cortisol in the eel and shows that elevated levels of this hormone down-regulate AQP3 mRNA expression in the gill in a similar manner to SW-acclimation. However, the smaller magnitude of the changes in branchial AQP3 expression induced by cortisol-infusion (around a 60% decrease), in comparison to those occurring following SW-acclimation, suggest that other factors must also contribute to AQP3 down-regulation. In a similar fashion to the regulation of AQP1 by cortisol, changes in AQP3 expression following hormone infusion appear to be tissue-specific, as little effect was seen on the level of AQP3 expression in the intestine. Again the apparent lack of change in intestinal AQP3 expression following cortisol-infusion mimicked the invariant level of intestinal AQP3 mRNA abundance following SW-acclimation. PMID- 17353013 TI - Feedback control of thyrotropin secretion in the chicken: thyroid hormones increase the expression of hypophyseal somatostatin receptor types 2 and 5. AB - We have studied the involvement of the somatostatin receptor type 5 (SSTR5) in the control of thyrotropin (TSH) release in the chicken. Hypothalamic somatostatin (SS-14) is known to inhibit both thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH)-induced TSH secretion. Studies using receptor-specific agonists have indicated that the inhibitory effect of SS-14 on TRH-induced TSH release is mediated by SSTR2 and SSTR5. Using the same agonists, we were able to demonstrate the involvement of SSTR5 in the inhibition of the in vitro CRH-induced TSH secretion by SS-14. Subsequently, we determined hypophyseal SSTR5 mRNA expression during the last week of embryonic development using real time PCR. SSTR5 mRNA levels were low until day 19 of incubation, but between day 19 and hatching SSTR5 mRNA expression increased 3-fold. Since this increase coincides with the increasing plasma T(3) levels towards hatching, and a similar ontogenetic expression pattern was found for SSTR2, we quantified hypophyseal SSTR2 and SSTR5 mRNA expression levels in chicken embryos treated with thyroid hormones. Injection of thyroid hormones was indeed found to increase the expression of both mRNAs significantly. We hypothesize that the negative feedback exerted by the increasing plasma T(3) levels towards hatching is at least in part mediated by an increased expression of SSTR2 and SSTR5. PMID- 17353014 TI - Nitric oxide modulates gonadal and adrenal function in Japanese quail Coturnix coturnix japonica. AB - Nitric oxide (NO) a gaseous neurotransmitter is reported to play an important role in controlling the release of luteinizing hormone releasing hormone (LHRH) in mammalian system. But its role has not been investigated in birds, where photoperiod plays an important role in regulating gonadal development. To investigate the effect of NO on gonadal and adrenal function of Japanese quail, in the first experiment, 3-weeks-old sexually immature quail received NO donor sodium nitroprusside (SNP, 5mg/100g body weight) orally or nitric oxide synthase (NOS) inhibitor N-nitro L-arginine methyl ester (L-NAME, 25 microg/100g body weight) intraperitoneally for 13 days in continuous condition of light (LL). Thereafter treated quail along with their respective controls were shifted to long day length (LD 16:8) for 21 days when the study was terminated. Results indicate that SNP treatment stimulated and L-NAME suppressed body weight, cloacal gland volume (an androgen dependent sex accessory organ), testes (gonado-somatic index, spermatogenesis), epididymis (histology) and adrenal (weight, histology, cortico-medullary ratio) function as well as total nitrite and nitrate concentration in plasma, hypothalamus and testes. In the second experiment, two groups of 3-weeks-old birds were maintained in short day length (LD 6:18) or long day length (LD 16:8) for 5 weeks to induce gonadal suppression and stimulation, respectively. Thereafter birds of both the photoperiod were divided into two subgroups, the short day quail receiving normal saline (SD Con) or SNP (SD+SNP) while long day quail received normal saline (LD Con) or L-NAME (LD+L-NAME) for 13 days and were maintained in their respective photoperiods, until the termination of study (21 days post treatment period). SNP stimulated all the parameters even in short day condition and L-NAME suppressed in long day quail compared to their respective controls. These findings indicate positive control of NO on the gonad and adrenal function of Japanese quail which exhibits parallel adrenal-gonad relationship. Further, NO donor induces long day effects while NOS inhibitor mimics short day effects. It is concluded that NO may not only regulate hypothalamo-hypophyseal-gonadal and -adrenal axis of Japanese quail but may also modulate its photosexual responses. PMID- 17353015 TI - Evolution of the CT/CGRP family: comparative study with new data from models of teleosts, the eel, and cephalopod molluscs, the cuttlefish and the nautilus. AB - In mammals, alternative splicing of the calcitonin gene generates two distinct peptides: calcitonin (CT), synthesised in the thyroid C cells and involved in the regulation of calcium metabolism, and calcitonin gene-related peptide (CGRP), brain neuromediator synthesised in the peripheral and central nerves. CGRP is well represented and molecularly conserved during evolution whereas CT has not been detected in any of the invertebrates analysed so far. In order to better understand the evolution of this CT/CGRP peptide family we reviewed the major data concerning its evolution from the literature and our recent data obtained in models of teleosts and cephalopod molluscs. The presence of both CGRP-like molecules and its specific bindings sites in the central nervous system of eel, cuttlefish and nautilus, suggests that the brain neurotransmitter role of CGRP could represent an ancient role in metazoa, already present in cephalopods and conserved among vertebrates, as still observed in mammals. In contrast, the presence of CGRP specific binding sites, and not the peptide itself, in the gills suggests an endocrine role for CGRP, in cephalopods and teleosts, that may have been lost during the evolution of the tetrapod lineage. These data, and the absence of CT-like molecules that we observed in cephalopods, support the hypothesis that CGRP represents the ancestral molecule of the CT/CGRP family, appeared in metazoa before the vertebrate emergence. The distinction between CT and CGRP receptors appears to be an event posterior to the emergence of ecdysozoan and lophotrochozoan protostomes, probably in relation to the CT appearance. The evolution of the CT/CGRP peptide family is probably similar to the evolution of the CT/CGRP receptor family. In fact, the genic duplication that induced the appearance of the two separate molecules, CT and CGRP, may constitute an event close to that, which induced the appearance of the two specific receptors. These events remain to be further studied in order to better understand the peptide and receptor evolution of the CT/CGRP family. PMID- 17353016 TI - Expression of secretory phospholipase A2s in human atherosclerosis development. AB - Secretory phospholipase A2s (sPLA2s) contribute to the hydrolysis of phospholipid. Among them, sPLA2-IIA, -V, and -X have been regarded as enhancers of lipid accumulation in arterial intima. However, the distribution and production of the other types of sPLA2 in human aortic wall remain unclear. Therefore, in this study, the distribution and production of seven types of sPLA2 including IIA, IID, IIE, IIF, III, V, and X in atherosclerosis development in the human aorta were comprehensively examined by immunohistochemistry and in situ hybridization (ISH). The extent of sPLA2s expression increased with atherosclerosis development, but only sPLA2-IIF was never observed in the normal aorta. Double-immunostaining demonstrated that sPLA2-V expression was limited to smooth muscle cells (SMCs), although the other sPLA2s were expressed in both macrophages and SMCs. ISH using sPLA2 cDNAs revealed that the expression pattern of each mRNA was consistent with the results of immunohistochemistry for each corresponding sPLA2. These results indicate that the seven types of sPLA2 are expressed with various patterns in all stages of atherosclerosis development and may play an atherogenic role through degradation of phospholipid. PMID- 17353017 TI - Is excessive daytime sleepiness a predictor of carotid atherosclerosis in sleep apnea? AB - OBJECTIVE: To elucidate the relationship between excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. METHODS: One hundred and forty-seven patients (102 males) with snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high sensitivity C-reactive protein and fibrinogen and four sonographic indices: intima media thickness (IMT) of the common carotid artery (CCA), IMT from the bulb to the internal carotid artery (ICA), combined IMT measurements from all segments and a plaque score. EDS was assessed by the Epworth Sleepiness Scale (ESS). Pearson correlation analysis, intergroup comparison (ANOVA) and two multiple regression models explored associations between confounders, surrogate markers and EDS. RESULTS: Forty-four patients had no OSA (apnea-hypopnea index AHI<5h(-1)), 27 mild (5-15), 25 moderate (15-30) and 51 severe OSA (>30). The ESS significantly distinguished severe OSA from non-OSA patients (p=0.003). It showed significant correlations with the BMI, HbA1c, systolic RR, the AHI, sleep time spent with an oxygen saturation <90%, the respiratory arousal index, IMT of the CCA and combined IMT measurements, but no correlation with serum markers. The ESS was found to be an independent predictor of CCA-IMT in the pre-polysomnographic multiple regression model (p=0.008), but not in the post-polysomnographic model after including respiratory variables. CONCLUSION: EDS is associated with obesity, diabetes and all respiratory variables in OSA patients and may serve as an independent predictor of carotid atherosclerosis before polysomnography. PMID- 17353018 TI - Biomechanics of the rabbit knee and ankle: muscle, ligament, and joint contact force predictions. AB - Mathematical models of small animals that predict in vivo forces acting on the lower extremities are critical for studies of musculoskeletal biomechanics and diseases. Rabbits are advantageous in this regard because they remodel their cortical bone similar to humans. Here, we enhance a recent mathematical model of the rabbit knee joint to include the loading behavior of individual muscles, ligaments, and joint contact at the knee and ankle during the stance phase of hopping. Geometric data from the hindlimbs of three adult New Zealand white rabbits, combined with previously reported intersegmental forces and moments, were used as inputs to the model. Muscle, ligament, and joint contact forces were computed using optimization techniques assuming that muscle endurance is maximized and ligament strain energy resists tibial shear force along an inclined plateau. Peak forces developed by the quadriceps and gastrocnemius muscle groups and by compressive knee contact were within the range of theoretical and in vivo predictions. Although a minimal force was carried by the anterior cruciate and medial collateral ligaments, force patterns in the posterior cruciate ligament were consistent with in vivo tibial displacement patterns during hopping in rabbits. Overall, our predictions compare favorably with theoretical estimates and in vivo measurements in rabbits, and enhance previous models by providing individual muscle, ligament, and joint contact information to predict in vivo forces acting on the lower extremities in rabbits. PMID- 17353019 TI - Rapid headspace solid-phase microextraction-gas chromatographic-time-of-flight mass spectrometric method for qualitative profiling of ice wine volatile fraction. II: Classification of Canadian and Czech ice wines using statistical evaluation of the data. AB - The previously developed and optimized headspace solid-phase microextraction (HS SPME)-GC-time-of-flight (TOF) MS analytical method for the determination of compounds with a wide range of polarities and volatilities was successfully used in this study to characterize and classify a large set of ice wines according to their origin, grape variety and oak or stainless steel fermentation/ageing conditions, based on a statistical evaluation (principal component analysis (PCA)) of the measured data. More than 130 ice wine samples collected directly from Canadian and Czech wine producers were analyzed in this study. The SPME step was beneficially carried out utilizing the new-generation super elastic divinylbenzene/Carboxen/polydimethylsiloxane (DVB/CAR/PDMS) 50 microm/30 microm fiber assembly. One fiber was used for the whole sequence of ice wine samples, control and blank experiments, which consisted of more than 600 individual extraction/injection cycles. Utilizing the high-speed TOF analyzer, full spectral information within the range of 35-450 u was collected for the entire GC run (as short as 4.5 min) without compromising in the detection sensitivity, as compared to other scanning mass analyzers operated in selected ion monitoring or MS(n) mode to achieve similar sensitivity. The identification of analytes was performed by a combination of the linear temperature-programmed retention index (LTPRI) approach with the comparison of the obtained spectra with three libraries included in the ChromaTOF software. A total of 201 peaks were tentatively assigned as ice wine aroma components and 58 of those compounds were evaluated in all of the examined samples. PMID- 17353020 TI - Numerical model for the investigation of dual-flow in a spiral counter-current chromatography column. AB - In dual-flow counter-current chromatography (DF-CCC), the two immiscible liquids are flowing in opposite directions in the coil. The method allows for the continuous separation of two solutes. In this study a numerical model was developed to allow for the detailed investigation of flow in such columns. The mesh model of the presented DF spiral column was developed in line with an existing experimental model. The paper presents results during the early filling stages for different rotation directions. These clearly illustrate the performance of the developed model by (1) confirming the importance of flowing the lighter phase from tail to head and the heavier phase from head to tail and (2) by visualising mixing waves and the recognised back and forth "swish-swash" motion as present in CCC in that operating mode. PMID- 17353021 TI - Nano-liquid chromatography analysis of dansylated biogenic amines in wines. AB - In this work, the simultaneous analysis of 10 biogenic amines (ethanolamine, methylamine, tryptamine, 2-phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine and spermine) in wines by nano-liquid chromatography (nano LC) using UV detection and a capillary bidentate C(18) column of 100 microm I.D. is proposed. The 10 selected amines, which are the most important to be determined in wine samples, were derivatized with dansyl-chloride (Dns-Cl) previous to their nano-LC determination. Excess of the derivatizing agent as well as other components of the samples were eliminated by the use of an on-line cleaning step employing a C(18) trapping column which also provided a pre concentration effect. The mobile phase composed of acetonitrile, water, acetic acid and triethylamine (TEA) mixture was pumped at a low flow rate (634 nL/min). Limits of detection (LODs) achieved ranged between 18.3 and 48.3 ng/mL; while calibration curves showed good linearity (R(2)>0.9924). The method was applied to the analysis of this group of amines in white and red wine samples after suitable treatment with polyvinylpyrrolidone (PVP) and extraction with C(18) cartridges. PMID- 17353022 TI - Use of compressed fluids for sample preparation: food applications. AB - This review attempts to provide an updated overview (including works published till June 2006) on the latest applications of compressed fluids as sample preparation techniques for food analysis. After a general review of the principles of supercritical fluid extraction (SFE) and pressurized liquid extraction (PLE; also called accelerated solvent extraction, ASE or subcritical water extraction, SWE, when water is employed as extraction solvent), the principal applications of such techniques in the mentioned fields of food and natural products are described, discussing their main advantages and drawbacks. PMID- 17353023 TI - Extracellular signal-regulated kinase (ERK) and nitric oxide synthase mediate intrathecal morphine-induced nociceptive behavior. AB - Intrathecal (i.t.) administration of morphine at a high dose of 60nmol into the spinal lumbar space in mice produces a severe hindlimb scratching followed by biting and licking. Nitric oxide (NO) is thought to play an important role in signal transduction pathways that enhance nociceptive transmission in the spinal cord. The present study was designed to determine whether high-dose i.t. morphine could influence the activation of the extracellular signal-regulated kinase (ERK), a mitogen-activated protein (MAP) kinase in neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) activation. Both 7-NI and TRIM, selective inhibitors of nNOS, resulted in a dose-dependent inhibition of high-dose i.t. morphine-induced behavior. The selective iNOS inhibitor W1400 in relatively large doses inhibited in a non dose-dependent manner. The i.t. injection of morphine evoked a definite activation of ERK in the lumbar dorsal spinal cord. Behavioral experiments showed that U0126 (0.5-2.5nmol), a MAP kinase-ERK inhibitor, dose dependently attenuated the behavioral response to i.t. morphine. In mice treated with high-dose morphine, 7-NI was very effective in blocking ERK activation, whereas W1400 had no effect. Taken together, these results suggest that the behavioral response to high-dose i.t. morphine may be triggered by the nNOS-ERK pathway in the dorsal spinal cord. PMID- 17353024 TI - The genetical bandwidth mapping: a spatial and graphical representation of population genetic structure based on the Wombling method. AB - Characterizing the spatial variation of allele frequencies in a population has a wide range of applications in population genetics. This article introduces a new nonparametric method, which provides a two-dimensional representation of a structural parameter called the genetical bandwidth, which describes genetic structure around arbitrary spatial locations in a study area. This parameter corresponds to the shortest distance to areas of significant allele variation, and its computation is based on the Womble's systemic function. A simulation study and application to data sets taken from the literature give evidence that the method is particularly demonstrative when the fine-scale structure is stronger than the large-scale structure, and that it is generally able to locate genetic boundaries or clines precisely. PMID- 17353025 TI - Cellular proteins of Microcystis aeruginosa inhibiting coagulation with polyaluminum chloride. AB - Cyanobacterial growth in semi-closed water areas such as reservoirs brings about a coagulation inhibition in a drinking water treatment system, but the inhibitory substances and mechanisms involved have yet to be elucidated. In this study, proteins having a high affinity with polyaluminum chloride (PACl) were isolated from organic substances produced by Microcystis aeruginosa with the affinity chromatography technique. Both extracellular organic matter (EOM) and cellular organic matter (COM) disturbed the flocculation of suspended kaolin with PACl, but it was likely that nonproteinous substances in EOM cause the reduction of coagulation effciency. In contrast, proteins in COM were obtained as possible inhibitory substances for the coagulation with PACl. These proteins could consume PACl in the coagulation process due to the formation of chelate complexes between these inhibitory proteins and the coagulant. The consumption of PACl by cyanobacterial proteins could be one of the important causes of the increase in coagulant demand. PMID- 17353026 TI - Oxidation of two organophosphorous insecticides by the photo-assisted Fenton reaction. AB - The photocatalytic degradation of two selected insecticides (dimethoate and methyl parathion) has been studied using the photo-assisted Fenton reaction. The degradation kinetics were studied under different conditions such as iron's and oxidant's concentration, temperature and inorganic ions. The degradation rates proved to be strongly influenced by these parameters. The replacement of hydrogen peroxide with peroxydisulfate was also tested in a photo-Fenton-like reaction. This system achieved high degradation rates of the selected compounds. Intermediate products formed during photocatalytic treatment were identified by means of solid-phase extraction (SPE) coupled to gas chromatography-mass spectroscopy techniques (GC-MS). Eight possible by-products were identified for parathion methyl and three for dimethoate formed through mainly oxidation and dealkylation reactions. Mineralization studies showed also that the photo-Fenton and the photo-Fenton-like systems are able to achieve mineralization of the insecticides. However, complete detoxification is achieved only in the presence of the photo-Fenton reagent. PMID- 17353027 TI - Photocatalytic degradation of reactive black 5 in aqueous solutions: Effect of operating conditions and coupling with ultrasound irradiation. AB - The degradation of reactive black 5 (RB 5), a representative diazo dye found in textile effluents, by means of ultraviolet irradiation (9W UVA) over TiO(2) suspensions, ultrasound irradiation (80kHz, 135W) and their combined application was investigated. Several commercial TiO(2) catalysts were screened and an anatase Hombicat UV 100 sample exhibited considerable activity in terms of solution decoloration, COD and ecotoxicity reduction. Photocatalytic degradation increased with increasing TiO(2) loading (in the range 0.05-1g/L) and decreasing dye concentration (in the range 120-20mg/L) and solution pH (in the range 9-2.6). At the typical conditions employed in this study (60mg/L dye, 0.25mg/L catalyst, ambient pH=5.8, oxygen sparging), complete decoloration was achieved after 60min of reaction. Addition of H(2)O(2) up to 0.01M hindered degradation, scavenging the photogenerated holes and hydroxyl radicals. Ultrasound irradiation resulted in low decoloration, e.g. less than 10% after 60min at 60mg/L dye and oxygen sparging and slightly improved under an argon atmosphere. The simultaneous application of ultraviolet and ultrasound irradiation resulted in increased decoloration compared to that achieved by photocatalysis and sonolysis operating separately; moreover, the overall sonophotocatalytic effect was greater than the additive effect of the two processes, implying possible synergy. PMID- 17353028 TI - Inactivation of Escherichia coli O157:H7 during thermophilic anaerobic digestion of manure from dairy cattle. AB - Inactivation of the pathogenic Escherichia coli serotype O157:H7 and a non pathogenic E. coli strain isolated from dairy cattle manure was evaluated with batch tests at 50 and 55 degrees C in biosolids from a thermophilic anaerobic digester treating the manure. Using differential-selective plating on sorbitol MacConkey (SMAC) agar to quantify E. coli, the decline in concentrations of both the sorbitol-negative (putative E. coli O157:H7) and sorbitol-positive (putative non-pathogenic E. coli) organisms followed a model that assumed there was a heat sensitive fraction and a heat-resistant fraction. Inactivation rates of the heat sensitive fractions were similar for both colony types at each temperature, suggesting that wild-type E. coli can be used as an indicator of inactivation of serotype O157:H7. The decimal reduction time for the heat-sensitive fractions was in the order of 10min at 55 degrees C and ranged from approximately 1-3h at 50 degrees C. Concentrations of heat-resistant organisms at 55 degrees C were 1.4 1.7log(10)cfu/mL. Confirmatory analyses conducted on 30 randomly selected colonies of heat-resistant sorbitol-negative cells from treatment at 55 degrees C indicated that none were serotype O157:H7, nor were they E. coli. Similar analyses on 10 sorbitol-negative isolates from untreated manure indicated that none were serotype O157:H7, although 16S rRNA gene sequence analysis indicated that eight were E. coli or closely related enteric bacteria. These findings suggest that plating on differential-selective media to quantify E. coli, including serotype O157:H7, in effluent samples from thermophilic anaerobic digestion can lead to false positive results. Therefore, more specific methods should be used to evaluate the extent of thermal inactivation of both pathogenic and non-pathogenic E. coli in manure treatment systems. PMID- 17353029 TI - Experimental and modeling approach to study sorption of dissolved hydrophobic organic contaminants to microbial biofilms. AB - A biofilm reactor was developed to investigate the sorption of polycyclic aromatic hydrocarbons (PAH) as model compounds for hydrophobic organic contaminants (HOC) to intact microbial biofilms at environmentally realistic concentrations. When operated as a differential column batch reactor, the system can be used to study the thermodynamics as well as the kinetics of the exchange of HOC between an aqueous phase and microbial biofilms. Organic carbon normalized partition coefficients (K(oc)) for phenanthrene, fluoranthene and pyrene were at the lower end of those known for other organic sorbents. Intra-biofilm diffusion coefficients (D) were calculated from decrease in solute concentration over time using a model for diffusion through a plane sheet and ranged from 0.23 to 0.45x10(-9)cm(2)s(-1) for the three PAH. These diffusion coefficients are about four orders of magnitude lower than those reported in literature for free aqueous solution. These data and the experimental approach presented here are useful to assess the importance of microbial biofilms for exchange processes of HOC in heterogeneous systems such as water distribution systems, membranes and aquifers, sewer systems or surface soils. PMID- 17353030 TI - Kinetics of the oxidation of cylindrospermopsin and anatoxin-a with chlorine, monochloramine and permanganate. AB - Cyanobacteria produce toxins that may contaminate drinking water sources. Among others, the presence of the alkaloid toxins cylindrospermopsin (CYN) and anatoxin a (ANTX) constitutes a considerable threat to human health due to the acute and chronic toxicity of these compounds. In the present study, not previously reported second-order rate constants for the reactions of CYN and ANTX with chlorine and monochloramine and of CYN with potassium permanganate were determined and the influence of pH and temperature was established for the most reactive cases. It was found that the reactivity of CYN with chlorine presents a maximum at pH 7 (rate constant of 1265 M(-1)s(-1)). However, the oxidation of CYN with chloramine and permanganate are rather slow processes, with rate constants <1 M(-1)s(-1). The first chlorination product of CYN was found to be 5-chloro-CYN (5-Cl-CYN), which reacts with chlorine 10-20 times slower than the parent compound. The reactivity of ANTX with chlorine and chloramines is also very low (k<1M(-1)s(-1)). The elimination of CYN and ANTX in surface water was also investigated. A chlorine dose of 1.5 mg l(-1) was enough to oxidize CYN almost completely. However, 3 mg l(-1) of chlorine was able to remove only 8% of ANTX, leading to a total formation of trihalomethanes (TTHM) at a concentration of 150 microg l(-1). Therefore, chlorination is a feasible option for CYN degradation during oxidation and disinfection processes but not for ANTX removal. The permanganate dose required for CYN oxidation is very high and not applicable in waterworks. PMID- 17353031 TI - Bovid postcranial ecomorphological survey of the Laetoli paleoenvironment. AB - Here we report on a bovid postcranial ecomorphological survey of the fossil assemblages from the Plio-Pleistocene site of Laetoli, Tanzania. A global sample of extant bovids (n=205), cervids (n=14), and tragulids (n=5) from seven known habitat types constitutes the comparative data set. All long bones, carpals, tarsals, and phalanges were measured. Discriminant function analyses (DFA) were conducted in order to evaluate the ability of each element to accurately predict habitat affiliation. The baseline of chance accuracy for DFAs (i.e., the percentage of correct predictions that can be expected when habitat assignments are randomized) served as the cut-off point between good and bad habitat predictors. A total of 22 elements yielded percentages of correct classification over the baseline of accuracy, and these were extended to the Laetoli fossil assemblages. Summaries of the number of specimens predicted to belong to each habitat type were used to reconstruct the paleoenvironment. The results indicate that, at the time of the deposition of the Laetolil Beds, the area had heavy woodland-bushland cover with some lighter tree and bush cover and grass available. These results lend strong support to recent suggestions that the area was on the more wooded end of the habitat spectrum, contra initial conclusions that it represented a mosaic of more open habitats. The results also indicate that, during the deposition of the Ndolanya Beds, the environment had become more open and the grassland component of the environment had increased significantly. Light woodland-bushland and an abundance of grass cover dominated the landscape, although tracts of land with denser vegetation likely existed. This conclusion agrees with earlier suggestions that the area was a semiarid bushland. PMID- 17353032 TI - The variability of regional airflow obstruction within the lungs of patients with asthma: assessment with hyperpolarized helium-3 magnetic resonance imaging. AB - BACKGROUND: It is unknown whether focal changes of airflow obstruction within the lungs of patients with asthma vary or are fixed in location with time or repeated bronchoconstriction. With hyperpolarized helium-3 magnetic resonance (H(3)HeMR) imaging, the airspaces are depicted and focal areas of airflow obstruction are shown as "ventilation defects." OBJECTIVE: To investigate the regional changes of airflow obstruction with time and repeated bronchoconstriction. METHODS: H(3)HeMR and spirometry were performed before (pre) and immediately after (post) methacholine challenge in 10 young patients with asthma on 2 days that were 7-476 days (mean, 185.3 +/- 37.2 days) apart. Pair-wise image comparisons were performed to determine the change in location of ventilation defects within the lung and their change in size. RESULTS: When comparing premethacholine versus premethacholine and postmethacholine versus post-methacholine images of the 2 days, 41% +/- 10% and 69% +/- 5% (P = .017) of defects, respectively, were in the same location, and of those, 69% +/- 12% and 43% +/- 5% (P = .022), respectively, did not change size. Comparing premethacholine versus postmethacholine images, 58% +/- 9% of defects were in the same location on day 1 and 73% +/- 7% (P = .088) on day 2. On both days, the percent increase in defect number from premethacholine to postmethacholine was much greater than the percent decrease in spirometric values (P < .001). CONCLUSION: Many of the ventilation defects persisted or recurred in the same location with time or repeated bronchoconstriction, suggesting that the regional changes of airflow obstruction are relatively fixed within the lung. CLINICAL IMPLICATIONS: The findings give new insight into the regional airflow variability within the lungs of patients with asthma. PMID- 17353033 TI - New molecular targets for the treatment of neutrophilic diseases. AB - Increased neutrophils are a feature of airway inflammation in patients with chronic obstructive pulmonary disease and in some patients with asthma, particularly patients with more severe disease, during exacerbations and with cigarette smoking. Because neutrophilic inflammation may be detrimental, there are several new approaches to inhibiting neutrophilic inflammation. Neutrophilic inflammation is resistant or poorly responsive to corticosteroids, so different anti-inflammatory approaches are needed. Blocking neutrophil chemotactic factors such as leukotriene B(4) and IL-8 and related cysteine-X-cysteine chemokines by blocking receptor for leukotriene B(4) 1 and receptor for cysteine-X-cysteine chemokines 2 receptors is an approach that is currently being investigated. Other approaches include blocking adhesion molecules such as E-selectin. Inhibiting phosphodiesterase-4, nuclear factor-kappaB, or p38 mitogen-activated protein kinase is another approach that inhibits the production of cysteine-X-cysteine chemokines. Antioxidants, long-acting beta(2)-agonists, and activators of histone deacetylase may also be effective. PMID- 17353034 TI - Antiviral activity of human beta-defensin 3 against vaccinia virus. PMID- 17353035 TI - Interactions between breast-feeding, specific parental atopy, and sex on development of asthma and atopy. AB - BACKGROUND: The influence of breast-feeding on the risk of developing atopy and asthma remains controversial. OBJECTIVE: To examine asthma and atopy outcomes by sex, reported specific parental history of atopy, and breast-feeding. METHODS: In a birth cohort, we examined childhood asthma and atopy (positive skin prick tests) by sex and breast-feeding in relation to maternal and paternal atopy. Interactions were explored in logistic regression models. RESULTS: For boys, breast-feeding (odds ratio [OR], 1.63; 95% CI, 0.93-2.87; P = .09) and maternal atopy (OR, 1.95; 95% CI, 0.93-4.08; P = .08) were each associated with atopy at age 13 years. Breast-feeding increased the risk for atopy among boys with paternal atopy (OR, 7.39; 95% CI, 2.21-24.66) compared with non-breast-fed boys with paternal atopy, but did not significantly further increase risk among subjects with maternal atopy. For girls, breast-feeding (OR, 0.74; 95% CI, 0.41 1.31) and maternal and paternal atopy were not independent risk factors for atopy at age 13 years. However, breast-feeding increased the risk for atopy in girls with maternal atopy (OR, 3.13; 95% CI, 1.20-8.14) compared with non-breast-fed girls with maternal atopy. There was no such effect among subjects with paternal atopy. Results for the outcome of asthma followed a similar pattern. CONCLUSION: The influence of breast-feeding on development of atopy and asthma differs by sex and by maternal and paternal atopy, and is most significant among subjects at lower baseline risk. CLINICAL IMPLICATIONS: Analyses of environmental risk factors for asthma and atopy should be stratified by specific parental atopy and sex. PMID- 17353036 TI - The impact of government advice to pregnant mothers regarding peanut avoidance on the prevalence of peanut allergy in United Kingdom children at school entry. AB - BACKGROUND: In June 1998, the United Kingdom government suggested that atopic pregnant and breast-feeding mothers and their infants should avoid peanuts. OBJECTIVE: We report the prevalence of peanut sensitization in the first school cohort (2003-2005) to have been conceived after the advice was issued. METHOD: A total of 1072 mother-child pairs were studied in school. Children with positive peanut skin prick test results to peanut had peanut challenges. RESULTS: Overall, 61% of 957 mothers recalled hearing the advice about peanuts in 1998. This figure was unaffected by maternal atopic status. Only 36 mothers (3.8%) followed the Government's advice by stopping the consumption of peanuts while pregnant. Maternal atopy had no effect on peanut consumption while breast-feeding. Mothers were less likely to change their diet if having a second or subsequent child compared with mothers having their first child (odds ratio 0.635, 95% Cis, 0.543 0.743; P < .01). Thirty children (2.8%; 95% CIs, 1.8% to 3.8%) had a positive peanut skin prick test result. Twenty children (1.8%; 95% CIs, 1.1% to 2.7%) were shown to have peanut allergy. This is the highest prevalence for peanut allergy recorded to date. CONCLUSIONS: The prevalence of peanut sensitization in this cohort is 2.8%, and peanut allergy now affects 1.8% of British children at school entry. It is difficult to ascertain any impact (either positive or negative) of the United Kingdom government advice on the prevalence of peanut allergy in British children aged 4-5 years from 2003 to 2005. CLINICAL IMPLICATIONS: It remains uncertain if peanut avoidance during pregnancy and breast-feeding has any effect on the prevalence of peanut allergy in children. PMID- 17353037 TI - Pathergy response to skin prick testing. PMID- 17353039 TI - Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. AB - BACKGROUND: Severe lower respiratory infections (LRIs) and atopic sensitization have been identified as independent risk factors for asthma. OBJECTIVE: The nature of potential interactions between these risk factors was the subject of this study. METHODS: A community-based cohort of 198 children at high atopic risk was followed from birth to 5 years. All episodes of acute respiratory illness in the first year were recorded and postnasal aspirates were collected for viral identification. History of wheeze and asthma was collected annually, and atopy was assessed at 6 months, 2 years, and 5 years. RESULTS: A total of 815 episodes of acute respiratory illness were reported, and 33% were LRIs. Viruses were detected in 69% of aspirates, most commonly rhinoviruses (48.3%) and respiratory syncytial virus (10.9%). At 5 years, 28.3% (n = 56) had current wheeze, and this was associated with wheezy [odds ratio (OR), 3.4 (1.2-9.7); P = .02] and/or febrile LRI [OR, 3.9 (1.4-10.5); P = .007], in particular those caused by respiratory syncytial virus or rhinoviruses [OR, 4.1 (1.3-12.6); P = .02]. Comparable findings were made for current asthma. Strikingly these associations were restricted to children who displayed early sensitization (< or =2 years old) and not observed in nonatopic patients or those sensitized later. CONCLUSION: These data suggest viral infections interact with atopy in infancy to promote later asthma. Notably the occurrence of both of these events during this narrow developmental window is associated with maximal risk for subsequent asthma, which suggests a contribution from both classes of inflammatory insults to disease pathogenesis. CLINICAL IMPLICATIONS: Protection of "high-risk" children against the effects of severe respiratory infections during infancy may represent an effective strategy for primary asthma prevention. The potential benefits of these strategies merit more careful evaluation in this age group. PMID- 17353040 TI - Development and cross-sectional validation of the Childhood Asthma Control Test. AB - BACKGROUND: For children younger than 12 years old with asthma, there are several quality-of-life instruments, clinical diaries, and questionnaires assessing symptoms; however, a validated tool for assessing asthma control is currently lacking. OBJECTIVE: To develop and validate the Childhood Asthma Control Test (C ACT), a self-administered tool for identifying children aged 4-11 years whose asthma is inadequately controlled. METHODS: A 21-item questionnaire was administered to 343 patients with asthma and their caregivers, randomly assigning 75% (n = 257) for development and cross-sectional validation of the tool and 25% (n = 86) to a confirmatory sample. Stepwise logistic regression was used to reduce the 21 items to those best able to discriminate control as defined by the specialist's rating of asthma control. RESULTS: Seven items were selected from regression analyses of the development sample to comprise the C-ACT. The scores of each item were summed for a total score (0-27), with lower scores indicating poorer control. Summed scores discriminated between groups of patients differing in the specialists' rating of asthma control (F = 36.89; P < .0001), the need for change in patients' therapy (F = 20.07; P < .0001), and % predicted FEV(1) (F = 2.66; P = .0494). A score of 19 indicated inadequately controlled asthma (specificity 74%, sensitivity 68%). These analyses were confirmed in the confirmatory sample. CONCLUSION: The C-ACT is a validated tool to assess asthma control and identify children with inadequately controlled asthma. CLINICAL IMPLICATIONS: The C-ACT can be valuable in clinical practice and research based on its validation, ease of use, input from the child and caregiver, and alignment with asthma guidelines. PMID- 17353041 TI - IL-10-treated dendritic cells decrease airway hyperresponsiveness and airway inflammation in mice. AB - BACKGROUND: IL-10 affects dendritic cell (DC) function, but the effects on airway hyperresponsiveness (AHR) and inflammation are not defined. OBJECTIVE: We sought to determine the importance of IL-10 in regulating DC function in allergen induced AHR and airway inflammation. METHODS: DCs were generated from bone marrow in the presence or absence of IL-10. In vivo IL-10-treated DCs from IL-10(+/+) and IL-10(-/-) donors pulsed with ovalbumin (OVA) were transferred to naive or sensitized mice before challenge. In recipient mice AHR, cytokine levels, cell composition of bronchoalveolar lavage (BAL) fluid, and lung histology were monitored. RESULTS: In vitro, IL-10-treated DCs expressed lower levels of CD11c, CD80, and CD86; expressed lower levels of IL-12; and suppressed T(H)2 cytokine production. In vivo, after transfer of OVA-pulsed IL-10-treated DCs, naive mice did not have AHR, airway eosinophilia, T(H)2 cytokine increase in BAL fluid, or goblet cell metaplasia when challenged, and in sensitized and challenged mice IL 10-treated DCs suppressed these responses. Levels of IL-10 in BAL fluid and numbers of lung CD4(+)IL-10(+) T cells were increased in mice that received OVA pulsed IL-10-treated DCs. Transfer of IL-10-treated DCs from IL-10-deficient mice were ineffective in suppressing the responses in sensitized and challenged mice. CONCLUSIONS: These data demonstrate that IL-10-treated DCs are potent suppressors of the development of AHR, inflammation, and T(H)2 cytokine production; these regulatory functions are at least in part through the induction of endogenous (DC) production of IL-10. CLINICAL IMPLICATIONS: Modification of DC function by IL-10 can attenuate lung allergic responses, including the development of AHR. PMID- 17353042 TI - Antigen coupled with Lewis-x trisaccharides elicits potent immune responses in mice. AB - BACKGROUND: Glycoproteins containing Lewis-x (Le(x)) trisaccharides are often associated with the host's adaptive T(H)2-type immunity, but the mechanisms underlying the T(H)2-biased response are at present unclear. OBJECTIVE: The modulatory effect of Le(x) or its glycoconjugates on IgE/T(H)2 responses was investigated. METHODS: The levels of serum antibodies and cytokines were analyzed by means of ELISA, RT-PCR, or both. RESULTS: In C3H mice Le(x) coupled with BSA (Le(x)-BSA) elicited higher levels of specific IgE and IgG1, but not IgG2a, which were associated with increased levels of splenic T(H)2 cytokines when compared with those seen in BSA-sensitized mice. In BALB/c mice sensitized with Le(x)-BSA or Le(x) mixed with ovalbumin, significantly increased levels of specific IgE and IgG2a antibodies were found concomitant with reduced levels of serum IL-12p70. These effects were attenuated in IL-12-deficient BALB/c mice. Le(x) and an isomer, Le(y), but not other isomers, inhibited the production of LPS-induced IL 12p70, associated with a significant reduction of nuclear NF-kappaB, in bone marrow-derived dendritic cells from BALB/c mice, suggesting that Le(x)-induced suppression of IL-12p70 results in an enhanced T(H)2 response. The addition of mannan, a known ligand for dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin, abrogated the suppressive effect of Le(x) trisaccharides. CONCLUSION: These results provide evidence for a potential role of Le(x) trisaccharides in shaping the immune responses through, at least in part, its suppressive effect on IL-12p70 production. Considering the relative ubiquity of glycoproteins with Le(x) or similar oligosaccharides, including plant derived (or food-derived) allergens, these findings might have a broad implication. CLINICAL IMPLICATIONS: The adjuvant activity of Le(x) trisaccharides might aid in vaccine design and might be important in determining the allergenicity of proteins containing this or other similar structures. PMID- 17353043 TI - Endogenously generated hydrogen peroxide induces apoptosis via mitochondrial damage independent of NF-kappaB and p53 activation in bovine embryos. AB - Hydrogen peroxide (H(2)O(2)) has been implicated as a key molecule in arresting embryonic development; however, its mechanism of action is not fully established. The aim of the present study was to determine the chronological generation of H(2)O(2) from oocyte to morula, and to examine the relationship of H(2)O(2) with loss of mitochondrial membrane potential, nuclear factor kappa-B (NF-kappaB), p53, caspase-3 activation, and cell death in bovine embryos in vitro. Accordingly, superoxide anion radicals were detected between 32 and 120 h after in vitro fertilization, but higher percentages of oxygen radicals were found in non-competent embryos (n=73, 22 to 34%) than in competent embryos (n=73, 0 to 1%; P<0.005). Similarly, H(2)O(2) levels were higher in non-competent embryos (n=249, 39 to 71%) than in competent embryos (n=278, 0 to 3.4%) at all developmental stages tested (P<0.005). The percentage of cells with apoptotic morphology were higher in non-competent embryos (n=411, 3 to 54%) than in competent embryos (n=306, 0 to 0.6%; P<0.005). Based on assessment of mitochondrial membrane potential, competent embryos (n=305) had the highest percentages of JC-1 staining (31 to 50%) when compared with non-competent embryos (n=411; 1 to 15%, P<0.005). The percentage of activation of general caspases was different in non-competent embryos (n=291, 15 to 57%) when compared to competent embryos (n=304, 0 to 0.5%; P<0.005). Pharmacological inhibition of caspase-3, NF-kappaB and p53 triggered aberrant embryo cytoplasmic fragmentation with and without nuclei. We concluded that the sequential mechanism of O(2)(-) and H(2)O(2) generation, mitochondrial damage, caspase activation, and apoptotic morphology might be responsible for the developmental arrest of preimplantation embryos. PMID- 17353044 TI - Placental expression of the membrane form of folate binding protein during pregnancy in swine. AB - Previous experiments indicated that secreted (s) and membrane (m) forms of folate binding protein (FBP) are present in the intrauterine environment of the pig. Our previous studies indicated that the two forms were produced sequentially; the secreted form was present in the intrauterine glands until Day 20 of gestation, whereas binding analysis indicated that folate binding increased dramatically in placental membranes until Day 50 of gestation. However, the cell types expressing mFBP have not been investigated. In this experiment, uterine wall sections from Day 20, 35, 50, 70, 90, and 105 of gestation were collected at slaughter and fixed, and subjected to in situ hybridization analysis for mFBP expression. The mFBP mRNA was expressed by both columnar and cuboidal epithelia of the placental folds and expression appeared to be similar throughout gestation. Therefore, the placenta expressed mFBP from Day 35 of gestation onward, consistent with the concept that sFBP and mFBP occur sequentially during gestation in swine, and that placental mFBP expression plays a role in folate transport after a functional chorioallantoic placenta is established (between Day 20 and 35). PMID- 17353045 TI - The dimensional stability of dental impression materials following immersion in disinfecting solutions. AB - OBJECTIVES: This investigation examined the effect of several disinfectant systems upon the dimensional stability of a range of common dental impression materials. A new disinfection process based upon hypochlorous acid was one of those examined (Sterilox). METHODS: Test specimens of commercially available impression materials from the following categories were investigated: alginates, addition-cured silicones, condensation-cured silicones and polyether. Three disinfection regimes were tested: sodium hypochlorite 5.25%, Perform ID and Sterilox. A custom-built automatic laser micrometer was used to measure the dimensions of sample discs of the test materials before disinfection, immediately after and then following 24h storage. Analysis of variance was employed to identify statistically significant differences within groups and across groups. RESULTS: All the disinfection routines tested resulted in acceptable levels of dimensional stability within the category of normal use of each impression material. All the materials tested can be disinfected with 10% Sterilox without undergoing unacceptable levels of dimensional change. SIGNIFICANCE: All the disinfection routines tested resulted in acceptable levels of dimensional stability within the category of normal use of each impression material. PMID- 17353046 TI - A three layer structure model of fluoridated enamel containing CaF2, Ca(OH)2 and FAp. AB - OBJECTIVES: The aim of this study was to develop a molecular-based structural model of human teeth after fluoridation with a commonly used amine fluoride, which is highly significant for understanding the effectiveness of topical fluoridation. METHODS: This multi method study used XPS, MAS-NMR and Raman spectroscopy measurements in order to analyze powdered synthetic hydroxylapatite (HAp), powdered human enamel samples and human enamel pieces treated with amine fluoride (Elmex) fluid) in vitro. RESULTS: The results lead to a complete structural characterization of the fluoridation products. A three layer composition of calcium hydroxide, calcium fluoride and an apatite species was identified. SIGNIFICANCE: The top surface CaF(2) layer acts as a fluoride reservoir and covers a layer of antimicrobial effective Ca(OH)(2). Ca(OH)(2) is a well-known therapeutic agent. However, up to now Ca(OH)(2) has not been described as a reaction product after topical fluoridation. Below the Ca(OH)(2) layer an acid resistant apatite species (FAp) was detected which reached directly into the bulk enamel HAp species. The three layer composition identified helps to understand the influence of fluoride application in the pathogenic mechanisms of tooth decay. Each component in this newly suggested structure model has a specific function, which explains how topical fluoridation of enamel reduces dental caries and influences its pathogenic mechanisms. PMID- 17353048 TI - Ultrastructure of human placental tissue after 6 h of normoxic and hypoxic dual in vitro placental perfusion. AB - The dual in vitro perfusion model of human placental tissue allows the study of different aspects of placental function, such as metabolism, transport and secretion of proteohormones, cytokines and prostaglandins. The integrity of the perfused placental tissue is an important parameter to validate the perfusion system. Using light and electron microscopy, the morphology of villous tissue was examined before and after six hours of normoxic (n=10) vs. hypoxic (n=10) perfusion. An apical shift of the rough endoplasmic reticulum and occasional vacuoles were found in the syncytiotrophoblast of the terminal villi, the exchange area of the placenta. No unexpected pathological findings were seen before the perfusion experiments and only slight changes with moderate distension of the endoplasmic reticulum after 6 h of normoxic perfusion. After hypoxic perfusions, distinct ultrastructural alterations, such as oedematous villous stroma, swollen or completely destroyed cell organelles (e.g., mitochondria and endoplasmic reticulum), multiple vacuoles inside syncytio- and cytotrophoblasts as well as the microvilli were seen, which leads to an impairment of the placental barrier and other functions. The ultrastructural examination of placental tissue before and after dual in vitro perfusion broadens the knowledge of physiological and pathophysiological processes in the perfused placenta and may be a beneficial part of regular validation. PMID- 17353047 TI - Neomycin prevents enzyme-mediated glycosaminoglycan degradation in bioprosthetic heart valves. AB - Bioprosthetic heart valves (BHVs) derived from glutaraldehyde crosslinked porcine aortic valves are frequently used in heart valve replacement surgeries. However, BHVs have limited durability and fail either due to degeneration or calcification. Glycosaminoglycans (GAGs), one of the integral components of heart valve cuspal tissue, are not stabilized by conventional glutaraldehyde crosslinking. Previously we have shown that valvular GAGs could be chemically fixed with GAG-targeted chemistry. However, chemically stabilized GAGs were only partially stable to enzymatic degradation. In the present study an enzyme inhibitor was incorporated in the cusps to effectively prevent enzymatic degradation. Thus, neomycin trisulfate, a known hyaluronidase inhibitor, was incorporated in cusps via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N hydroxysuccinimide (EDC/NHS) chemistry followed by glutaraldehyde crosslinking (NEG). Controls included cusps crosslinked with either EDC/NHS followed by glutaraldehyde (ENG) or only with glutaraldehyde (GLUT). NEG group showed improved resistance to in vitro enzymatic degradation as compared to GLUT and ENG groups. All groups showed similar collagen stability, measured as a thermal denaturation temperature by differential scanning calorimetry (DSC). The cusps were implanted subdermally in rats to study in vivo degradation of GAGs. NEG group preserved significantly more GAGs than ENG and GLUT. NEG and ENG groups showed reduced calcification than GLUT. PMID- 17353049 TI - Decreased induction of IL-1beta in fibroblast-like synoviocytes: a possible regulatory mechanism maintaining joint homeostasis. AB - The response of fibroblast-like synoviocytes (FLS) to inflammatory stimuli was compared to their, respectively, derived dermal fibroblasts (DF) to determine whether regulatory controls exist within FLS to insure normal joint homeostasis. We further analyzed whether the loss of the normal regulatory controls present within the FLS could predispose to the development of non-rheumatic joint disease (non-RA). Primary fibroblast cell lines were generated from synovial and skin tissue from ten rheumatoid arthritis (RA) and ten non-RA patients. Cell lines were pulse labeled with [(35)S]-methionine and stimulated with TNFalpha or IL 1beta. Protein synthesis of IL-1beta, IL-6 and IL-8 was quantitated following immunoprecipitation. Gene expression was determined by Northern blot analysis. We noted, IL-1beta was minimally detected in FLS under nonstimulated conditions. In response to stimulation with IL-1beta or TNFalpha, production of IL-1beta was found to be 3.5 and 5-fold lower in FLS, respectively, when compared to DF from the same individual. In contrast, the production of IL-6 and IL-8 in FLS upon stimulation was 3-fold and 1.6-fold higher, respectively, than in DF. Furthermore, induced IL-1beta production in FLS, normalized relative to their, respectively, stimulated DF, was 2.5 times higher in non-RA versus RA-derived cells (p=0.032), an effect noted even after several passages of growth. Our data suggest that inductive expression of IL-1beta in FLS is under specific inhibitory control. Increased production of IL-1beta in FLS of susceptible individuals may lead to a higher risk of developing severe joint damage even in the absence of systemic inflammation. PMID- 17353050 TI - Complement in experimental autoimmune encephalomyelitis revisited: C3 is required for development of maximal disease. AB - Complement per se has been shown to play an important role in demyelinating disease but controversy remains regarding the role of C3 in the development and progression of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. In this study, we used C3(-/-) mice to confirm previous findings that C3 is required for full development of EAE. Furthermore, C3(+/-) mice (with serum C3 levels 50% that of wild-type mice) developed EAE with a severity intermediate between wild-type and C3(-/-) mice. Importantly transfer of wild-type encephalitogenic T cells to C3(-/-) mice resulted in attenuated EAE. C3(-/-) mice with EAE had fewer CD4(+) and CD8(+) T cells in the CNS and 50% fewer of these cells produced IFN-gamma compared to wild-type mice. When treated with anti-CD3 antibody, CD4(+) T cells from wild-type and C3(-/-) mice had similar activation profiles as judged by IFN-gamma production and CD25 and CD69 expression, indicating there is no gross or intrinsic defect in T cells from C3( /-) mice. T cells from primed C3(-/-) mice proliferated comparably to that of control T cells on re-stimulation with MOG peptide. Our results confirm a requirement for C3 for maximal development of EAE and suggest that receptors for C3-derived activation fragments might be a viable therapeutic target for prevention and treatment demyelinating disease. PMID- 17353051 TI - Phage display of chelating recombinant antibody libraries. AB - High affinity and discriminating specificity are important parameters for any successful antibody based targeting strategy. We herein describe a system for the construction and subsequent selection of affinity-optimised chelating recombinant antibodies (CRAbs) from a randomised filamentous phage-display inter-scFv linker library. Using a simple, robust and highly degenerate tandem scFv cloning strategy a phage-display library of CRAbs with varied inter-scFv linkers was constructed and characterised. The library consisted of two single-chain Fvs (scFvs) of well characterised anti-lysozyme antibodies D1.3 and HyHEL-10(TF), specific for distinct non-overlapping epitopes, separated by flexible polypeptide linkers of varying lengths and sequences. The use of a stringent affinity-based selection strategy quickly led to the enrichment of CRAbs with a restricted set of linker lengths (16-21 amino acids) which agrees very closely with previously described crystal structure data, affinity measurements and mathematical modelling. This CRAb linker phage-display selection strategy is a widely applicable approach for the selection of very high affinity CRAbs for pairs of scFvs against potentially any target antigen, complementing the more arbitrary affinity maturation approaches based on random mutagenesis. PMID- 17353052 TI - Reproducibility of macular thickness and volume using Zeiss optical coherence tomography in patients with diabetic macular edema. AB - PURPOSE: To evaluate optical coherence tomography (OCT) reproducibility in patients with diabetic macular edema (DME). DESIGN: Prospective 1-day observational study. PARTICIPANTS: Two hundred twelve eyes of 107 patients with DME involving the macular center by clinical examination and OCT central subfield thickness of > or =225 microm. METHODS: Retinal thickness was measured with the OCT3 system, and scans were evaluated by a reading center. Reproducibility of retinal thickness measurements was assessed, and 95% confidence intervals (CIs) for a change in thickness were estimated. MAIN OUTCOME MEASURES: Reproducibility of OCT-measured central subfield thickness. RESULTS: Reproducibility was better for central subfield thickness than for center point thickness (half-width of the 95% CI for absolute change, 38 microm vs. 50 microm, and for relative change, 11% vs. 17%, respectively; P<0.001). The median absolute difference between replicate measurements of the central subfield was 7 microm (2%). Half-widths of the 95% CI for a change in central subfield thickness were 22, 23, 33, and 56 microm for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. When expressed as percentage differences between 2 measurements, half-widths of the 95% CI for a change in central subfield thickness were 10%, 10%, 10%, and 13% for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. We were unable to identify an effect on reproducibility of central subfield measurements with respect to the presence of cystoid abnormalities, subretinal fluid, vitreomacular traction, or reduced visual acuity. Reproducibility was better when both scans had a standard deviation (SD) of the center point of <10.0% (half width of the 95% CI for change, 33 microm vs. 56 microm; P<0.001). CONCLUSIONS: Reproducibility is better for central subfield thickness measurements than for center point measurements, and variability is less with retinal thickness when expressed as a percent change than when expressed as an absolute change. A change in central subfield thickness exceeding 11% is likely to be real. Scans with an SD of the center point of > or =10.0% are less reproducible and should be viewed with caution when assessing the validity of an observed change in retinal thickness in patients with DME. PMID- 17353053 TI - Automated optimal detection and classification of neural action potentials in extra-cellular recordings. AB - Determination of single unit spikes from multiunit spike trains plays a critical role in neurophysiological coding studies which require information about the precise timing of events underlying the neural codes that are the basis of behavior. Searching for optimal spike detection strategies has therefore been the focus of many studies over the past two decades. In this study we describe and implement an algorithm for the optimal real time detection and classification of neural spikes. The algorithm consists of three steps: noise analysis, template generation and real time detection and classification. The first step involves estimating the background noise statistics. In this step, a "cap-fitting" algorithm is used to automatically detect a spike free segment and then the mean, standard deviation and autocorrelation function of the noise are computed. The second step involves generating optimal templates of the spikes from a segment containing both noise and multiunit activity. In this step, a generalized matched filter is used to isolate a set of preliminary spikes from the noise. The first principal component of previously recorded templates is used as the deterministic signal. The preliminary spikes are then clustered in a sub-space spanned by the first three principal components to form new templates. The third step uses these templates for the real time spike detection and classification. In this step the incoming data are projected into a lower dimensional space that is designed to maximally separate the signal from the noise energy. This algorithm provides an accurate estimate of the signal to noise ratio and provides an accurate estimate of spike times and spike shapes. PMID- 17353054 TI - Inter-individual variability in optimal current direction for transcranial magnetic stimulation of the motor cortex. AB - We evaluated inter-individual variability in optimal current direction for biphasic transcranial magnetic stimulation (TMS) of the motor cortex. Motor threshold for first dorsal interosseus was detected visually at eight coil orientations in 45 degrees increments. Each participant (n=13) completed two experimental sessions. One participant with low test-retest correlation (Pearson's r<0.5) was excluded. In four subjects, visual detection of motor threshold was compared to EMG detection; motor thresholds were very similar and highly correlated (0.94-0.99). Similar with previous studies, stimulation in the majority of participants was most effective when the first current pulse flowed towards postero-lateral in the brain. However, in four participants, the optimal coil orientation deviated from this pattern. A principal component analysis using all eight orientations suggests that in our sample the optimal orientation of current direction was normally distributed around the postero-lateral orientation with a range of 63 degrees (S.D.=13.70 degrees). Whenever the intensity of stimulation at the target site is calculated as a percentage from the motor threshold, in order to minimize intensity and side-effects it may be worthwhile to check whether rotating the coil 45 degrees from the traditional posterior lateral orientation decreases motor threshold. PMID- 17353055 TI - Replication of infectious bursal disease virus in macrophages and altered tropism of progeny virus. AB - We serially passaged classical infectious bursal disease virus (cIBDV) and antigenic variant IBDV (vIBDV) in an avian macrophage cell line, NCSU cells, referred as mcIBDV and mvIBDV respectively and examined the in vitro and in vivo characteristics of the macrophage-adapted viruses. NCSU adapted viruses caused earlier destruction of NCSU cells than the unadapted viruses. Nitric oxide (NO) was detected earlier in cultures infected with mcIBDV and mvIBDV than in cultures infected with cIBDV and vIBDV. cIBDV and vIBDV were able to infect DF-1 cells, a chicken embryo fibroblast cell line, only after one replication cycle in NCSU cells. The genetic basis of altered tropism of progeny virus from NCSU cells infected cultures was not identified. No aa substitutions were observed in hypervariable region of VP2 of cIBDV and vIBDV passaged 1 time in NCSU cells whereas both mcIBDV and mvIBDV had multiple aa substitutions. To assess protective efficacy of mcIBDV and mvIBDV, embryonated chicken eggs were inoculated with mcIBDV and mvIBDV at embryonation day 18 (ED 18) and challenged with a virulent cIBDV at 3 weeks of age. mcIBDV and mvIBDV were immunogenic and generated antibody responses and provided 100% protection against cIBDV. PMID- 17353056 TI - Children with language problems in a speech and hearing clinic: background variables and extent of language problems. AB - OBJECTIVE: Analysis of a clinical population referred for language analysis in terms of background variables and extent of language problems. DESIGN: Descriptive study. MATERIALS AND METHODS: Children referred to a speech and hearing clinic because of assumed language problems were analyzed with standardized tests for language comprehension (Dutch version of the Reynell Developmental Comprehension Scale) and language production (Schlichting test for sentence development). A language problem was defined when the language quotient score differed 1.3S.D. from the mean (quotient scores< or =80). Furthermore, potential risk factors for language problems were compiled (gender, prematurity, birth weight, family composition, familial aggregation, parental education and daycare/home care). RESULTS: Two hundred forty children, aged between 2 and 5 years of age were included in the study. A reliable language comprehension quotient (LCQ) was obtained in 204 children (85%) and a reliable sentence development quotient (SDQ) in 206 children (85%). In 35% of the children who were assumed to have language problems, adequate language development was found. The children with language problems differed from the children without language problems with regard to language problems in the family (more family aggregation). Also the former more frequently had parents with a low level of education and more often did not attend daycare. The total referred group differed from the Dutch population with regard to gender (more boys), more instances of low birth weight, more parents with middle and high educational level, more two-parent households, fewer siblings, and more frequent attendance at daycare. CONCLUSION: Parents with a low level of education more frequently have children with language problems. However, parents with a middle and high level of education are more often concerned about the language development of their child. As a consequence, the overestimation of language problems is a real issue in clinical practice. Normal variations in language development often are not considered. The analysis of compiled background variables indicates that language problems are genetically influenced (gender and family aggregation). Language input also is of importance (interactions with a language-competent parent or caregiver and peers): children with language problems less often attended daycare. PMID- 17353057 TI - Effects of the herbicide metazachlor on macrophytes and ecosystem function in freshwater pond and stream mesocosms. AB - The chloroacetamide metazachlor is a commonly used pre-emergent herbicide to inhibit growth of plants especially in rape culture. It occurs in surface and ground water due to spray-drift or run-off in concentrations up to 100 microgL( 1). Direct and indirect effects of metazachlor on aquatic macrophytes were investigated at oligo- to mesotrophic nutrient levels employing eight stream and eight pond indoor mesocosms. Five systems of each type were dosed once with 5, 20, 80, 200 and 500 microgL(-1) metazachlor and three ponds and three streams served as controls. Pronounced direct negative effects on macrophyte biomass of Potamogeton natans, Myriophyllum verticillatum and filamentous green algae as well as associated changes in water chemistry were detected in the course of the summer 2003 in both pond and stream mesocosms. Filamentous green algae dominated by Cladophora glomerata were the most sensitive organisms in both pond and stream systems with EC(50) ranging from 3 (streams) to 9 (ponds) microgL(-1) metazachlor. In the contaminated pond mesocosms with high toxicant concentrations (200 and 500 microgL(-1)), a species shift from filamentous green algae to the yellow-green alga Vaucheria spec. was detected. The herbicide effects for the different macrophyte species were partly masked by interspecific competition. No recovery of macrophytes was observed at the highest metazachlor concentrations in both pond and stream mesocosms until the end of the study after 140 and 170 days. Based on the lowest EC(50) value of 4 microgL(-1) for total macrophyte biomass, it is argued that single exposure of aquatic macrophytes to metazachlor to nominal concentrations >5 microgL(-1) is likely to have pronounced long-term effects on aquatic biota and ecosystem function. PMID- 17353058 TI - Physiological effects of polycyclic aromatic hydrocarbons on soft-shell clam Mya arenaria. AB - The aim of this study was to investigate the effects of polycyclic aromatic hydrocarbons (PAHs) on the physiological status of the bivalve Mya arenaria. Specimens were exposed to four different sources of PAHs: aluminium smelter soot, sediment from an industrial discharge pound, charcoal fine particles and dietary PAHs assessed by feeding clams with phytoplankton freshly impregnated with dissolved PAHs. The exposure period lasted 30 days and bivalves were let to recover for an additional 20 days. At days 8, 15, 30 and 50, immune parameters (phagocytic activity and efficiency) were monitored in haemocytes. Oxidative stress measures such as catalase and lipid peroxidation were quantified in digestive gland as well as concentrations of bioaccumulated PAHs. In a second experiment, clams were exposed to [(14)C]-pyrene via the phytoplankton, and the tissue distribution of radiolabelled compound was studied. Glycogen levels in gonad and digestive gland were also measured and gametogenesis stages were investigated. Results showed a high bioaccumulation in clams exposed to dietary PAHs and contaminated sediments. Tissue distribution of [(14)C]-pyrene revealed that the radiolabelled compound persisted mainly in the gonad during 14 days. A decrease of phagocytosis was observed in contaminated male clams. The lipid peroxidation (malondialdehyde) was found to increase in the digestive gland tissues of clams exposed to dietary PAHs, smelter soot and discharge, but no differences were observed in the catalase activity. A delay in gametogenesis occurred in all exposed males and in females contaminated with coke dust and dietary PAHs. Males were more sensitive than females to PAH exposure. A dysfunction in steroid synthesis is suspected to occur due to the exposure to all sources of PAHs. PMID- 17353059 TI - Plasmodium falciparum Na+/H+ exchanger activity and quinine resistance. AB - Mutations in the Plasmodium falciparum pfcrt gene cause resistance to the 4-amino quinoline chloroquine (CQ) and other antimalarial drugs. Mutations and/or overexpression of a P. falciparum multidrug resistance gene homologue (pfmdr1) may further modify or tailor the degree of quinoline drug resistance. Recently [Ferdig MT, Cooper RA, Mu JB, et al. Dissecting the loci of low-level quinine resistance in malaria parasites. Mol Microbiol 2004;52:985-97] QTL analysis further implicated a region of P. falciparum chromosome 13 as a partner (with pfcrt) in conferring resistance to the first quinoline-based antimalarial drug, quinine (QN). Since QN resistance (QNR) and CQR are often (but not always) observed together in parasite strains, since elevated cytosolic pH is frequently (but not always) found in CQR parasites, and since the chr 13 segment linked to QNR prominently harbors a gene encoding what appears to be a P. falciparum Na(+)/H(+) exchanger (PfNHE), we have systematically measured cytosolic pH and PfNHE activity for an extended series of parasite strains used in the QTL analysis. Altered PfNHE activity does not correlate with CQR as previously proposed, but significantly elevated PfNHE activity is found for strains with high levels of QNR, regardless their CQR status. We propose that either an elevated pH(cyt) or a higher vacuolar pH-to-cytosolic pH gradient contributes to one common route to malarial QNR that is also characterized by recently defined chr 13-chr 9 pairwise interactions. Based on sequence analysis we propose a model whereby observed polymorphisms in PfNHE may lead to altered Na(+)/H(+) set point regulation in QNR parasites. PMID- 17353060 TI - Differentiation of five tuna species by a multiplex primer-extension assay. AB - A novel methodology based on analysis of mtDNA-cytb diagnostic sites was performed to discriminate four closely related species of Thunnus (Thunnus alalunga, Thunnus albacares, Thunnus obesus and Thunnus thynnus) and one species of Euthynnus (Katsuwonus pelamis) genus in raw and canned tuna. The primers used in the preliminary PCR designed in well conserved region upstream and downstream of the diagnosis sites successfully amplified a 132bp region from the cytb gene of all the species taken into consideration. The sites of diagnosis have been interrogate simultaneously using a multiplex primer-extension assay (PER) and the results were confirmed by fragment sequencing. The applicability of the multiplex PER assay to commercial canned tuna samples was also demonstrated. The proposed test could be useful for detection of fraud and for seafood traceability. PMID- 17353061 TI - Preparation of liposomal gene therapy vectors by a scalable method without using volatile solvents or detergents. AB - A scalable and safe method was developed to prepare liposomal carriers for entrapment and delivery of genetic material. The carrier systems were composed of endogenously occurring dipalmitoylphosphatidylcholine (DPPC), negatively charged dicetylphosphate (DCP), cholesterol (CHOL) and glycerol (3%, v/v). Liposomes were prepared by a modified and improved version of the heating method in which no harmful chemical or procedure is involved. Anionic lipoplexes were formed by incorporating plasmid DNA (pCMV-GFP) to the liposomes by the mediation of calcium ions. Transfection efficiency and toxicity of the lipoplexes were evaluated in CHO-K1 cells using flow cytometry and MTT assay, respectively. Controls included DNA-Ca(2+) complexes (without lipids), anionic liposome-DNA complexes (with no Ca(2+)), and a commercially available cationic liposomal formulation. Results indicated fast and reproducible formation of non-toxic lipoplexes that possess long-term stability, high DNA entrapment capacity (81%) and high transfection efficiency. The lipoplex preparation method has the potential of large-scale manufacture of safe and efficient carriers of nucleic acid drugs. PMID- 17353062 TI - Relationship between smoking, white blood cell count and metabolic syndrome in Japanese women. AB - We found that cigarette smoking increased white blood cell count, and individuals which increased white blood cell count more likely to have metabolic syndrome in Japanese men. We investigated whether similar relationship can be observed also in women. We analyzed the data from 16,383 Japanese women who underwent general health screening. Age-adjusted logistic regression analysis showed that current smoking was positively associated with a highest white blood cell count quartile with an odds ratio of 2.40 (95% CI: 2.16-2.68, P<0.0001). The white blood cell count showed a graded association with metabolic syndrome. On the other hand, the association between current smoking and metabolic syndrome was no longer significant after subdividing the individuals into groups according to the white blood cell quartile. These data collectively suggested that the association between current smoking and metabolic syndrome is heavily confounded by certain factors that increase the circulating white blood cell count in Japanese women, as in men. PMID- 17353063 TI - The association of serum gamma glutamyltransferase with components of the metabolic syndrome in the Korean adults. AB - The metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease related to insulin resistance. Recently, serum gamma glutamyltransferase (GGT) has been proposed as a marker of oxidative stress and is associated with a marked increase in the risk of cardiovascular disease. So, we investigated the association between serum GGT and components of the metabolic syndrome in the Korean adults. A total 3246 adults (aged 20-70 years, 1622 men and 1624 women) who visited Center for Health Promotion in Pusan National University Hospital for a medical checkup were included. We measured serum GGT and lipid profiles, fasting glucose, fasting insulin and blood pressure. As the quartile of serum GGT increased, the number of components of MS and prevalence of MS were increased. Serum GGT was also increased according as the number of components of MS was increased. A significant correlation (r=0.200, p<0.001 in men and r=0.133, p<0.001 in women) was noted between the numbers of the components of the MS and serum GGT. In addition, serum GGT was correlated significantly (r=0.266, p<0.001 in men and r=0.264, p<0.001 in women) with homeostasis model assessment of insulin resistance (HOMA-IR). In linear regression model, serum GGT was mainly influenced by the concentration of triglycerides and fasting glucose. In conclusion, serum GGT is closely related with insulin resistance and the increased number of components of MS. Among components of MS, serum GGT may be more associated with dyslipidemia and abnormal glucose tolerance, suggesting that serum GGT has more relationship with hepatic insulin resistance regardless of non alcoholic fatty liver disease. PMID- 17353064 TI - FDG-PET and stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer. AB - PURPOSE: To investigate the utility of positron emission tomography (PET) in patients treated with stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) on prospective institutional trials. PATIENTS AND METHODS: Fifty-eight patients with medically inoperable stage I NSCLC who participated in prospective phase I and II trials of SBRT, had >or=2 years of follow-up, and received FDG-PET imaging are the focus of this evaluation. Fifty seven of 58 patients received pre-SBRT FDG-PET to confirm stage I status. All patients received stereotactic body frame immobilization and treatment with 7-10 photon beams. SBRT total doses ranged from 24 to 72Gy in three fractions. No elective nodal irradiation was undertaken. Regular follow-up with planned CT imaging was performed on all patients. Post-SBRT FDG-PET was not mandated by protocol and was typically ordered upon concern for disease recurrence. Thirty eight post-SBRT PET studies were performed in 28 patients at a median 17.3 months following SBRT. RESULTS: With a median follow-up of 42.5 months, the 3-year actuarial overall survival and local control for this select subset of our SBRT experience were 48.9% and 74.8%, respectively. Pre-SBRT FDG-PET SUV did not predict 3-year overall survival or local control. Fourteen of 57 patients eventually failed in nodal stations by CT and/or PET. Isolated first site of failure was nodal in 6 patients (10%). Out of 28 patients with post-SBRT PET, 4 (14%) had delayed PET imaging (22-26 months after SBRT) showing moderate hypermetabolic activity (SUV 2.5-5.07), but no evidence of local, nodal, or distant recurrence by clinical examination and conventional imaging performed 20 26 months following these concerning PET findings. CONCLUSIONS: Isolated nodal recurrence following PET-staged I NSCLC treated with SBRT is uncommon. Moderate post-SBRT PET hypermetabolic activity may persist 2 years following treatment without definite evidence of recurrence. Further study is needed to confirm these results in larger populations with longer follow-up. PMID- 17353065 TI - Is the titer of adipokinetic peptides in Leptinotarsa decemlineata fed on genetically modified potatoes increased by oxidative stress? AB - The level of adipokinetic hormones (AKHs) (Peram-CAH-I and II) in the corpora cardiaca and the hemolymph of Leptinotarsa decemlineata enormously increases in the adults fed on genetically modified potatoes containing either GNA lectin or Cry 3Aa toxin concomitant with increased oxidative stress in gut tissues. A similar enhancement of the AKH titer is achieved when the adults are injected with paraquat that evokes oxidative stress. On the other hand, an injection of exogenous AKH reduces oxidative stress biomarkers in the hemolymph by reducing protein carbonyls and enhancing reduced glutathione levels. These facts indicate that there is a feedback regulation between an oxidative stressor action and the level of AKH in the insect body, and that AKHs might be involved in the activation of an antioxidant protection mechanism. These results are to our knowledge, the first evidence for the involvement of AKHs in oxidative stress mitigation, in addition to a plethora of other roles. PMID- 17353066 TI - Neuroprotection conferred by astrocytes is insufficient to protect animals from succumbing to Japanese encephalitis. AB - Astrocytes play a key role in regulating aspects of inflammation and in the homeostatic maintenance of the central nervous system (CNS). However, the role of astrocytes in viral encephalitis mediated inflammation is not well documented. As Japanese encephalitis virus (JEV) infection is localized to neurons and considering the importance of astrocytes in supporting neuronal survival and function, we have exploited an experimental model of Japanese encephalitis (JE) to better understand the role of astrocytes in JE. Suckling mice pups were inoculated with the virus and 2 and 4 days later we analyzed a panel of molecules characteristic of reactive astrogliosis. We show that JEV infection increases the expression of astrocyte-specific glial fibrillary acidic protein (GFAP), the glutamate aspartate transporter (GLAST), glutamate transporter-1 (GLT-1) and ceruloplasmin (CP). The transcript levels of growth factors produced predominantly by activated astrocytes such as nerve growth factor (NGF) and ciliary neurotrophin factor (CNTF) were elevated following JEV infection. The transcript level of brain-derived neurotrophic factor (BDNF) was also elevated following JEV infection. Both NGF and CNTF were capable of preventing ROS mediated neuronal death following in vitro JEV infection to a certain extent. Taken altogether, these data indicate that increased astrogliosis following JEV infection is accompanied by the enhanced ability of astrocytes to detoxify glutamate, inactivate free radical and produce neurotrophic factors that are involved in neuronal protection. However, this elevated physiological state of astrocyte is insufficient in conferring neuroprotection, as infected animals eventually succumb to infection. The response of astrocytes to JE can be amplified to modulate the adaptive response of brain to induce neuroprotection. PMID- 17353067 TI - NPY in rat retina is present in neurons, in endothelial cells and also in microglial and Muller cells. AB - NPY is present in the retina of different species but its role is not elucidated yet. In this work, using different rat retina in vitro models (whole retina, retinal cells in culture, microglial cell cultures, rat Muller cell line and retina endothelial cell line), we demonstrated that NPY staining is present in the retina in different cell types: neurons, macroglial, microglial and endothelial cells. Retinal cells in culture express NPY Y(1), Y(2), Y(4) and Y(5) receptors. Retina endothelial cells express all NPY receptors except NPY Y(5) receptor. Moreover, NPY is released from retinal cells in culture upon depolarization. In this study we showed for the first time that NPY is present in rat retina microglial cells and also in rat Muller cells. These in vitro models may open new perspectives to study the physiology and the potential pathophysiological role of NPY in the retina. PMID- 17353068 TI - Hypersensitivity of aquaporin 4-deficient mice to 1-methyl-4-phenyl-1,2,3,6 tetrahydropyrindine and astrocytic modulation. AB - Aquaporin 4 (AQP4) is a predominant water channel protein in mammalian brains, which is localized in the astrocyte plasma membrane. AQP4 has gained much attraction due to its involvement in the physiopathology of cerebral disorders including stroke, tumor, infection, hydrocephalus, epilepsy, and traumatic brain injury. But there is almost no evidence whether abnormal AQP4 levels are associated with degenerative diseases, such as Parkinson's disease (PD). In our studies, we established PD animal models by administration of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine to test the hypothesis that abnormal AQP4 expression is involved in the pathophysiology of this disease. We show that mutant mice lacking AQP4 were significantly more prone to MPTP-induced neurotoxicity than their wild-type littermates. Furthermore, after administration of MPTP, astroglial proliferation and GDNF protein synthesis were inhibited by AQP4 deficiency. This study demonstrates that AQP4 is important in the MPTP neurotoxic process and indicates that the therapeutic strategy targeted to astrocytic modulation with AQP4 may offer a great potential for the development of new treatment for PD. PMID- 17353069 TI - Age-related spatial learning impairment is unrelated to spinophilin immunoreactive spine number and protein levels in rat hippocampus. AB - Age-related impairments in hippocampus-dependent learning and memory tasks are not associated with a loss of hippocampal neurons, but may be related to alterations in synaptic integrity. Here we used stereological techniques to estimate spine number in hippocampal subfields using immunostaining for the spine associated protein, spinophilin, as a marker. Quantification of the immunoreactive profiles was performed using the optical disector/fractionator technique. Aging was associated with a modest increase in spine number in the molecular layer of the dentate gyrus and CA1 stratum lacunosum-moleculare. By comparison, spinophilin protein levels in the hippocampus, measured by Western blot analysis, failed to differ as a function of age. Neither the morphological nor the protein level data were correlated with spatial learning ability across individual aged rats. The results extend current evidence on synaptic integrity in the aged brain, indicating that a substantial loss of dendritic spines and spinophilin protein in the hippocampus are unlikely to contribute to age-related impairment in spatial learning. PMID- 17353070 TI - KIBRA gene variants are associated with episodic memory in healthy elderly. AB - The first hypothesis free genome wide association study on cognition recently revealed the thus far unknown association of a single nucleotide polymorphism (SNP) of the KIBRA gene with episodic memory in healthy young and middle aged volunteers. Here, we report the first independent replication of this finding in an in-depth characterized sample of healthy elderly subjects. The effectsizes of the respective KIBRA SNP on memory even exceed those of the initial report. In parallel to the first study, the effect is restricted to hippocampus-related episodic memory without effects on frontal lobe function. The impact of KIBRA on memory is most likely of high relevance in elderly subjects as it is in young. PMID- 17353071 TI - mGluR5 metabotropic glutamate receptors and dyskinesias in MPTP monkeys. AB - Modulation of excessive glutamatergic transmission within the basal ganglia is considered as an alternative approach to reduce l-Dopa-induced dyskinesias (LIDs) in Parkinson's disease (PD). In this study receptor binding autoradiography of [3H]MPEP, a metabotropic glutamate receptor 5 (mGluR5) selective radioligand, was used to investigate possible changes in mGluR5 in the basal ganglia of l-Dopa treated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys having developed LIDs compared to animals in which LIDs was prevented by adjunct treatments. LIDs were associated with an increase of mGluR5 specific binding in the posterior putamen and pallidum (+41% and +56%) compared to controls. By contrast, prevention of dyskinesias was associated with an important decrease of mGluR5 specific binding in these areas (-37% and -48%) compared with dyskinetic animals. Moreover, an upregulation (+34%) of mGluR5 receptor binding was seen in the anterior caudate nucleus of saline treated MPTP monkeys. This study is the first to provide evidence that enhanced mGluR5 specific binding in the posterior putamen and pallidum may contribute to the pathogenesis of LIDs in PD. PMID- 17353072 TI - Treatment of acute otitis media with probiotics in otitis-prone children-a double blind, placebo-controlled randomised study. AB - BACKGROUND & AIMS: To examine whether probiotics would reduce the occurrence or duration of acute otitis media (AOM), or the nasopharyngeal carriage of otitis pathogens in otitis-prone children. METHODS: During this double-blind, placebo controlled, randomised, 24-week intervention, 309 otitis-prone children (10 months-6 years) consumed either one probiotic capsule (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve 99 and Propionibacterium freudenreichii JS) (n=155) or placebo (n=154) daily. Clinical examinations were carried out and nasopharyngeal samples taken three times. Parents recorded the symptoms of upper respiratory infection (URI) in a diary. RESULTS: Probiotic treatment did not reduce the occurrence (probiotic vs. placebo: 72% vs. 65%, OR=1.48, 95% CI 0.87 2.52, p=n.s.) or the recurrence ( three) of AOM episodes (18% vs. 17%, OR=1.04, 95% CI 0.55-1.96, p=n.s.). The median duration of AOM episodes was 5.6 (IQR 3.5 9.4) vs. 6.0 (IQR 4.0-10.5) days, respectively (p= n.s.). There was a tendency showing a reduction in the occurrence of recurrent (4 to 6) respiratory infections in the probiotic group (OR for 4 URIs: 0.56, 95%CI 0.31-0.99, p=0.046; OR for 6 URIs: 0.59, 95% CI 0.34 to 1.03, p=n.s.). Probiotics did not affect the carriage of Streptococcus pneumoniae or Haemophilus influenzae, but increased the prevalence of Moraxella catarrhalis (OR=1.79, 95% CI 1.06-3.00, p=0.028). CONCLUSIONS: Probiotics did not prevent the occurrence of AOM or the nasopharyngeal carriage of otitis pathogens in otitis-prone children. A tendency showing a reduction in recurrent respiratory infections must be confirmed in further studies. PMID- 17353073 TI - No reduction of spindle neuron number in frontoinsular cortex in autism. AB - It has been suggested that spindle neurons, an evolutionarily unique type of neuron, might be involved in higher-order social, emotional, and cognitive functions. As such, it was hypothesized that these neurons may be particularly important to the pathophysiology of autism, a disease characterized in part by disruption of higher-order social and emotional processing. Therefore, we conducted the first stereological investigation of the number of spindle neurons in autism, using the optical fractionator technique. Our results did not provide evidence of a reduction in spindle neuron number in frontoinsular cortex in autism. However, this study provides the first quantitative stereological data on spindle neuron number in autism. Future postmortem studies with larger sample sizes will likely be critical in elucidating the spared and defective neural systems underlying the autistic phenotype. PMID- 17353074 TI - Kava feeding in rats does not cause liver injury nor enhance galactosamine induced hepatitis. AB - Kava, like a number of herbals, has been associated with causing liver damage based on limited evidence. In contrast, the present study found that in rats, 3 mo feedings of two types of kava extracts (an acetone extract and an ethanol extract of the Samoan kava cultivar Ava Laau) at three different doses (31.25, 62.5 and 133 mg/kg diet) produced no liver injury based on serum markers of liver damage (sorbitol dehydrogenase activities, bile acid concentrations, and beta glucuronidase activities) and serum lipid peroxide readings. In fact, for some measurements and some kava doses, the injury marker readings were below control values. Moreover, for these same parameters, kava feeding did not enhance the effects of the hepatotoxin galacatosamine (500 mg/kg ip); some kava doses even showed modest protection against liver injury. Liver histology analysis showed no signs of kava causing or enhancing liver injury. Thus, this study does not support the concept that kava produces or aggravates liver injury. PMID- 17353075 TI - Emergency thoracotomy after cardiac arrest from blunt trauma is not always futile. AB - We report a case of blunt trauma leading to pulseless electrical activity (PEA) cardiac arrest that was successfully managed with emergency department thoracotomy. While the literature suggests an almost universally poor outcome from this clinical situation, in this case the patient survived with full neurological recovery. Several factors were present in this case, which have been reported as indicating an increased chance of good outcome. These were an arrest rhythm of sinus-based PEA, non-dilated reactive pupils and a short period of cardiopulmonary resuscitation. The case illustrates that in certain circumstances, emergency thoracotomy may not be futile after blunt trauma causing cardiac arrest. PMID- 17353076 TI - Personal protection equipment for biological hazards: does it affect tracheal intubation performance? AB - PURPOSE: Personal protection equipment (PPE) is recommended for use during airway management of patients with highly contagious respiratory tract illness. While its use in chemical hazards and its effect on airway management has been assessed previously, there has been no research assessing whether this equipment affects the ability to perform tracheal intubation. It is the intention of this investigation to answer this question. METHODS: Eighteen workers at various level of training were asked to wear three different types of PPE while performing four different types of tracheal intubation. The PPE used included the eye shield, face shield and the "Dustmaster". The intubation techniques were direct laryngoscopy, intubation through the intubating laryngeal mask (Fastrach) and flexible bronchoscopy using the eyepiece and an eyepiece with camera attached. We assessed the time to intubate as well as the incidence of oesophageal intubation. A short questionnaire was used to examine participants' subjective experiences of wearing the various types of PPE. RESULTS: There was no significant effect on the time to intubation for any of the methods studied. However, all subjects found that the face shield was uncomfortably hot to wear. Fibreoptic bronchoscopic intubation using the eyepiece was particularly difficult with all of the PPE used due to the distance of the subjects' eye from the eyepiece. CONCLUSION: Although the use of PPE may not affect the length of time to intubate manikins, certain types of PPE may be uncomfortable to wear and noisy. Further research is needed to investigate whether this could be a problem in the clinical setting or in actual difficult intubations. PMID- 17353077 TI - Taurine at early reperfusion significantly reduces myocardial damage and preserves cardiac function in the isolated rat heart. AB - OBJECTIVE: The Myocardial protective effects of taurine (TA) are well known. We investigated the optimal phase of giving taurine to reduce myocardial ischaemia reperfusion injury in isolated rat hearts. METHODS: Isolated rat hearts were subjected to 20 min of global ischaemia followed by 60 min of reperfusion under three different conditions: global ischaemia alone (control group; n=8); pre ischaemic administration of taurine (pre-TA group; n=8), perfusion with 10 mmol/L taurine for 10 min just before ischaemia; post-ischaemic administration of taurine (post-TA group; n=8), perfusion with 10 mmol/L taurine for the first 10 min of reperfusion. Ventricular functional and biochemical variables, the area at risk (AAR), and infarct size (IS) after reperfusion were compared between groups. RESULTS: Recovery of ventricular function in the post-TA group was significantly greater than that in the control and pre-TA groups in terms of left ventricular pressure and rate-pressure product. Lipid peroxide product as a marker of oxidant stress in the post-TA group was significantly less than that in the control and pre-TA groups. AAR relative to left ventricular area in the post-TA group was significantly less than that in the control and pre-TA groups. IS relative to AAR in the post-TA group was significantly less than that in the control group. CONCLUSION: Taurine administered before or after ischaemia prevents infarction; being a potent free radical scavenging antioxidant, it reduced myocardial injury and provided significantly better functional recovery when given immediately after reperfusion. PMID- 17353078 TI - Fluvastatin ameliorates endotoxin induced multiple organ failure in conscious rats. AB - OBJECTIVES: Sepsis is a severe inflammatory disorder that may lead to multiple organ failure. Lipopolysaccharide (LPS) is associated with Gram-negative sepsis and can activate monocytes and macrophages to release pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO) and anti inflammatory mediator such as interleukin-10 (IL-10). In this present study, we used fluvastatin, a HMG-CoA reductase inhibitor, to study its effects upon LPS induced endotoxic shock in conscious rats. METHODS: The experiments were designed that rats received an intravenous injection of 1mg/kg fluvastatin followed 10min later, by an intravenous injection of 10mg/kg Klebsiella pneumoniae LPS, the latter inducing endotoxic shock amongst conscious rats. Subsequently, the levels of certain biochemical variables and cytokines in serum were then measured during the ensuing 48-h period following sepsis. These included total cholesterol (TCH), triglyceride (TG), blood urea nitrogen (BUN), creatinine (Cre), creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate transferase (GOT), alanine transferase (GPT), tumor necrosis factor-alpha, interleukin-10 and nitric oxide. RESULTS: LPS significantly increased blood TG, BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-10 and NO levels but decreased the blood TCH level. Pretreatment of test rats with fluvastatin decreased blood levels of certain markers of organ injury, suppressed the release of TNF-alpha and increased IL-10, and NO levels following LPS treatment. Fluvastatin did not affect the blood TCH and TG level subsequent to the development of sepsis. CONCLUSIONS: Pre-treatment with fluvastatin suppresses the release of plasma TNF-alpha, increases plasma IL 10, and NO production, and decreases the levels of markers of organ injury associated with endotoxic shock, so ameliorating LPS-induced organ damage amongst conscious rats. PMID- 17353079 TI - Artificial acrylic finger nails may alter pulse oximetry measurement. AB - INTRODUCTION: Pulse oximetry is the most common technique to monitor oxygen saturation (SpO(2)) during intensive care therapy. However, intermittent co oximetry is still the "gold standard" (SaO(2)). Besides acrylic nails, numerous other factors have been reported to interfere with pulse oximetry. Data of measurements with artificial finger nails are not sufficiently published. MATERIALS AND METHODS: A prospective clinical-experimental trial in mechanically ventilated and critically ill patients of an ICU was performed. Patients were randomly assigned to either group S (S: Siemens pulse oximeter) or group P (P: Philips pulse oximeter) prior to the measurements. SpO(2) was determined in each patient three times alternately in standard ((N)SpO(2)) and sideways position at the natural nail ((N90)SpO(2)). For the reference measurements oxygen saturation was measured by means of a haemoximeter (co-oximetry). Thereafter, SpO(2) was obtained at the acrylic finger nail in the same way ((A)SpO(2) and (A90)SpO(2)). Bias was calculated as DeltaS=(N)SpO(2)-SaO(2) and DeltaS=(A)SpO(2)-SaO(2). Accuracy (mean difference) and precision (standard deviation) were used to determine the measurement discrepancy. P<0.05 was considered significant. RESULTS: Accuracy and precision without acrylic nails applied were comparable to SaO(2) in both groups (n.s.). With acrylic nails applied a bias of DeltaS=-1.1+/ 3.14% for group S (P=0.00522) and a bias of DeltaS=+0.8+/-3.04% for group P was calculated (n.s.). CONCLUSION: Acrylic finger nails may impair the measurement of oxygen saturation depending on the pulse oximeter used and may cause significant inaccuracy. Hence, removal of artificial acrylic finger nails may be helpful to assure an accurate and precise measurement with pulse oximetry. PMID- 17353080 TI - Anomalous coronary artery causing transmural ischaemia and ventricular tachycardia in a high school athlete. AB - A previously asymptomatic 15-year-old boy was treated at our institution after an episode of chest pain, palpitation, and syncope while playing in a high school soccer game. The patient's resting electrocardiogram was normal. A transthoracic echocardiogram showed an anomalous left main coronary artery originating from the right sinus of Valsalva. Contrast-enhanced multidetector computed tomography demonstrated clearly that the anomalous vessel coursed between the aorta and the pulmonary trunk (interarterial subtype). Treadmill testing registered several nonsustained polymorphic ventricular tachycardias and transmural myocardial ischaemia in the early recovery phase (ST-elevation up to 5mm in CM5 and V2 leads). The patient underwent bypass grafting. One year later, he remains asymptomatic, and new treadmill tests have been normal. In this patient, severe transmural myocardial ischaemia was detected, possibly due to collapse or vasospasm of the anomalous vessel, triggering life-threatening ventricular arrhythmias. PMID- 17353081 TI - Teaching acute care: a course for undergraduates. AB - AIM: To describe a course designed to help medical undergraduates develop the necessary competencies to recognise and manage acutely ill patients. MATERIALS AND METHODS: Primary description by the authors of the content, development and implementation of a course designed to teach competencies recommended by the Acute Care Undergraduate Teaching (ACUTE) project of the Resuscitation Council (UK) and Intercollegiate Board of Training in Intensive Care Medicine. The course format was designed to balance best teaching methods within the context of limited available teaching time and resources. Various components of the course were rated by 155 final year medical students who attended the course. RESULTS: A one and a half day integrated acute care course based on self-learning (course manual, CD-ROM, web material), lectures, interactive tutorials, skill stations and formative and summative assessment is described. The course addresses 55/71 (77%) of competencies considered important by the ACUTE project. It was well accepted by medical students and on a scale of 1 (poor) to 5 (excellent) median student ratings of various components of the course ranged from 4-5. CONCLUSION: The course offers a method of teaching acute care for medical undergraduates in an educationally sound, resource-efficient manner. PMID- 17353082 TI - What is the appropriate outcome for studies of treatments for out-of-hospital cardiac arrest-Revision of Table 2 and Appendix D. PMID- 17353083 TI - Supportive needs of parents confronted with sudden cardiac death--a qualitative study. AB - The death of a close family member is one of life's greatest tragedies. When death is sudden and unexpected, there is an increased risk of posttraumatic reactions and complicated mourning. Care of the bereaved is still often overlooked in medical training and clinical practise. The aim of this study was to elucidate the perceived support and the needs of bereaved parents confronted with sudden cardiac death (SCD) in a young son or daughter. Data were derived from a qualitative contents analysis of tape-recorded, in-depth interviews with bereaved parents confronted with SCD 5-12 years post-loss. The 20 deceased individuals were part of the Swedish forensic SCD cohort of 15-35 year olds from 1992 to 1999. One third of the parents had had no contact with the emergency department (ED), one third had been disappointed after meeting care-givers at the ED who did not act with sensitivity and consistency, while one third were more or less satisfied with the handling at the ED. A majority of the parents experienced a lack of follow-up care; they had been left mainly to themselves to find information and support. Four factors were identified as being particularly important for the parents: evidence, reconstruction, explanation and sensitivity. There is a need of better routines to help the suddenly bereaved. A model of the major needs and a plan for the support needed are proposed. PMID- 17353084 TI - Significant factors in predicting sustained ROSC in paediatric patients with traumatic out-of-hospital cardiac arrest admitted to the emergency department. AB - BACKGROUND: Paediatric patients with out-of-hospital cardiac arrest (OHCA) due to trauma pose difficult challenges in resuscitation. Trauma is a major cause of OHCA in children. The aim of this study was to determine which factors were related to predicting a sustained return of spontaneous circulation (ROSC) in paediatric OHCA patients with trauma. METHOD: This retrospective study comprised 115 paediatric patients (56 traumatic and 59 non-traumatic OHCA patients) aged younger than 18 years who had been admitted to the emergency department (ED) from January 2000 to December 2004. We analysed the demographic data and the factors that may have influenced sustained ROSC in the group of OHCA paediatric patients with trauma. The non-trauma group was established as a control group. Survival analysis was used to compare differences in survival rate between trauma and non trauma OHCA patients. Receiver operating characteristic (ROC) analysis was used to determine the significant in-hospital CPR duration related to sustained ROSC. RESULTS: Initial cardiac rhythm on arrival (P=0.005) and the duration of in hospital CPR (P<0.001) were significant factors. Patients with PEA or VF had higher rate of sustained ROSC than those with asystole (PEA: P=0.003, VF: P=0.03). In the survival analysis, OHCA children with trauma had a lower chance of survival than non-trauma children as the interval from the scene to the ER increased (P=0.008). Based on the ROC analysis, the cut-off values of in-hospital CPR duration were 25min in OHCA paediatric patients with trauma. CONCLUSION: Several significant factors relating to sustained ROSC were determined in the OHCA paediatric patients with trauma; most importantly, we found that in-hospital CPR may have to be performed for at least 25min to enable a spontaneous circulation to return. PMID- 17353085 TI - Long-term follow-up after abdominal pregnancy. PMID- 17353086 TI - Partial and complete expulsion of the Multiload 375 IUD and the levonorgestrel releasing IUD after correct insertion. AB - OBJECTIVE: The contraceptive efficacy of intrauterine devices (IUD) is thought to relate to the position of the IUD in the uterine cavity. Several trials examined the number of copper IUD expulsions, but none evaluated the partial and complete expulsion rate of the levonorgestrel-releasing device (LNG-IUD). STUDY DESIGN: This retrospective cohort study compares the dislocation rate of the Multiload 375 IUD (ML 375) and the LNG-IUD in 214 women (107 subjects with each IUD). Transvaginal ultrasound was used to monitor the IUD position immediately after insertion, after 6 weeks, and later on at intervals of 6 months. The observation period included 3631 cycles. RESULTS: We detected a significantly lower number of dislocations in LNG-IUD users. Previous expulsion was associated with a significantly higher risk for a re-expulsion in both IUD groups. Hypermenorrhea was not associated with an increased dislocation rate in LNG-IUD users. CONCLUSION: Expulsions are less likely to occur with the LNG-IUD, which might contribute to its contraceptive efficacy. PMID- 17353087 TI - LH/hCG action and development of ovarian cancer--a short review on biological and clinical/epidemiological aspects. AB - A link between infertility therapy, especially ovulation induction therapy using gonadotropins, and the development of ovarian cancer has long been an issue of debate since an epidemiological report supporting the possibility appeared in 1992. A number of clinical/epidemiological and biological studies, including a few that we conducted, have revealed various facts regarding this issue. The aim of this short review was to summarize the last 10 years findings and to address the implications of the debates on this issue. PMID- 17353088 TI - Human ovarian carcinoma cells generate CD4(+)CD25(+) regulatory T cells from peripheral CD4(+)CD25(-) T cells through secreting TGF-beta. AB - Increased CD4(+)CD25(+) regulatory T cells predicted poor prognosis in ovarian carcinoma patients. This study aimed to define whether soluble substances secreted by ovarian carcinoma could up-regulate the proportion of CD4(+)CD25(+) regulatory T cells. Similar to TGF-beta, the low MWF (<50kDa) of supernatant derived from SKOV3 could convert part of freshly isolated CD4(+)CD25(-) T cells into CD25(+) population with similar characters as natural CD4(+)CD25(+) regulatory T cells. To deplete TGF-beta in the low MWF by neutralizing anti-TGF beta would eliminate this transformation phenomenon. These results indicate that TGF-beta secreted by ovarian carcinoma cells owns vital function in the process of converting peripheral CD4(+)CD25(-) T cells into CD4(+)CD25(+) regulatory T cells, which may provide one immunotherapeutic target for ovarian cancer. PMID- 17353090 TI - Accumulation of Cd, Pb and Zn by 19 wetland plant species in constructed wetland. AB - Uptake and distribution of Cd, Pb and Zn by 19 wetland plant species were investigated with experiments in small-scale plot constructed wetlands, into which artificial wastewater dosed with Cd, Pb and Zn at concentrations of 0.5, 2.0 and 5.0mgl(-1) was irrigated. The results showed that the removal efficiency of Cd, Pb and Zn from the wastewater were more than 90%. Generally, there were tens differences among the 19 plant species in the concentrations and quantity accumulations of the heavy metals in aboveground part, underground part and whole plants. The distribution ratios into aboveground parts for the metals absorbed by plants varied also largely from about 30% to about 90%. All the plants accumulated, in one harvest, 19.85% of Cd, 22.55% of Pb and 23.75% of Zn that were added into the wastewater. Four plant species, e.g. Alternanthera philoxeroides, Zizania latifolia, Echinochloa crus-galli and Polygonum hydropiper, accumulated high amounts of Cd, Pb and Zn. Monochoria vaginalis was capable for accumulating Cd and Pb, Isachne globosa for Cd and Zn, and Digitaria sanguinalis and Fimbristylis miliacea for Zn. The results indicated that the plants, in constructed wetland for the treatment of wastewater polluted by heavy metals, can play important roles for removal of heavy metals through phytoextraction. Selection of plant species for use in constructed wetland will influence considerably removal efficiency and the function duration of the wetland. PMID- 17353091 TI - Nuclear translocation of the transcription factor STAT5 in the rat brain after systemic leptin administration. AB - Leptin binding to its functional receptor stimulates JAK-STAT-signaling pathway, which finally results in activation and nuclear translocation of transcription factors of the signal transducer and activator of transcription (STAT) family, namely of STAT3. Here we report for the first time that systemic treatment with leptin (5 mg/kg; intraperitoneal injection) also increased the number of nuclear STAT5 signals in the hypothalamus. In particular, the entire arcuate nucleus (ARC), the ventral premammilary nucleus (PMV), and the supraoptic nucleus (SO) showed an enhanced nuclear STAT5 translocation in response to leptin when compared to saline, 120 min after the respective injection. Co-localization studies revealed that a high percentage of those STAT5-responsive cells proved to be neurons. In addition, some astrocytes within the ARC showed nuclear STAT5 signals. The functional relevance of leptin-induced nuclear STAT5 activation in hypothalamic cells still has to be determined. PMID- 17353092 TI - Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10. AB - The heptapeptide Semax, an analogue of the N-terminal adrenocorticotropic hormone fragment (4-10) (ACTH(4-10)), has been shown to exert a number of neuroprotective effects. There are some investigations that connected these effects with the increase of neurotrophin gene expression under the peptide drug application in neuron cell cultures [M.I. Shadrina, O.V. Dolotov, I.A. Grivennikov, P.A. Slominsky, L.A. Andreeva, L.S. Inozemtseva, S.A. Limborska, N.F. Myasoedov, Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analogue, Neurosci. Lett. 308 (2001) (2) 115-118]. In this work, we examined the action of Semax on rapid changes of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in vivo. Male Wistar rats were treated for 1h with Semax (50 microg/kg, single intranasal application) and neurotrophin gene expression in rat brain was analyzed by real-time polymerase chain reaction (PCR). It was revealed that an intranasal application of Semax increased the expression of both neurotrophin genes in rat hippocampus. Bdnf gene expression also increased in the brainstem and cerebellum. Ngf gene expression decreased in rat frontal cortex. Thus, Semax induces rapid, gene- and region-specific changes in neurotrophin gene expression in normal rat brain. PMID- 17353093 TI - Electrophysiological correlates of memory processing in early Finnish-Swedish bilinguals. AB - Event-related desynchronization (ERD) and event-related synchronization (ERS) of the 1-30 EEG frequencies were studied in eight early Finnish-Swedish bilinguals during an auditory bilingual Sternberg memory task using Finnish-Swedish cognates as stimuli. Only subtle differences between languages were expected, since cognates have been assumed to have shared conceptual representations in the bilingual memory. Encoding elicited theta and alpha frequency ERS and beta frequency ERD responses in both languages. Retrieval elicited theta ERS and alpha and beta ERD responses. Some statistically significant differences between encoding and retrieval in Finnish versus Swedish emerged: greater theta and alpha ERS responses were observed during encoding in Swedish than during encoding in Finnish. During between-language retrieval, later-appearing theta ERS and alpha ERD responses were elicited as compared to within-language retrieval. These delayed oscillatory responses might reflect the involvement of central executive attentional functions in relation to language switching. PMID- 17353094 TI - The effect of a GABAA agonist muscimol on acoustic injury of the mouse cochlea. AB - Gamma-aminobutyric acid (GABA) is one of major inhibitory neurotransmitter in the central nervous system and constitutes the cochlear efferent system. Glutamate excitotoxicity is implicated in the pathogenesis of acoustic injury of the cochlea. The present work investigated whether GABA(A) agonist muscimol can alleviate acoustic injury. Mice were exposed to a 4 kHz pure tone of 128 dB SPL for 4h. Muscimol and/or bicuculline, a GABA(A) antagonist, were intraperitoneally administered immediately before the onset of acoustic overexposure. The threshold shifts of the auditory brainstem response (ABR) and cochlear morphology after acoustic overexposure were then evaluated. Muscimol significantly decreased the ABR threshold shift and inhibited swelling of the afferent dendrites induced by acoustic overexposure. In addition, bicuculline inhibited the effects of muscimol. These findings suggest that activation of GABA(A) receptors reduces acoustic injury of the cochlea. PMID- 17353096 TI - Vacuum-ultraviolet Gabor holography with synchrotron radiation. AB - We present the realization of high-resolution holographic microscopy using the original Gabor geometry and imaging with radiation in the vacuum-ultraviolet (VUV) spectral region. Synchrotron VUV radiation with a wavelength of 13.8 nm was focused on a small pinhole generating a highly divergent light cone suitable for digital in-line holography. Objects of different thickness and materials have been used to test the imaging properties of holographic microscopy in the VUV wavelength range. The effective numerical aperture was limited by the illuminated area of the detector, yielding a theoretical resolution below 1 microm and an experimental one of approximately 1 microm. PMID- 17353095 TI - Cholesterol level, statin use and Alzheimer's disease in adults with Down syndrome. AB - Adults with Down syndrome (DS) are at significantly higher risk of Alzheimer's disease (AD) than the general population, but there is considerable variability in age at onset. This study tested the hypothesis that total cholesterol (TC) levels are related to vulnerability, and that the use of statins may decrease risk. The relation of TC level and statin use to risk of AD was investigated in 123 Caucasian adults with DS. Evaluations included serial assessments of cognitive, adaptive and maladaptive behavior, medical records, and neurological examinations. Mean length of follow-up was 5.5 years [1.2-7.1] for the entire sample, 5.1 years [1.2-7.1] for subjects who developed dementia, and 5.6 years [1.5-7.1] for those who did not develop dementia. Controlling for covariates, participants with TC>or=200mg/dL were more than two times as likely to develop AD than subjects with lower TC [hazard rate (HR)=2.59, p=.029, 95% CI: 1.1, 6.1]. In contrast, participants with higher TC levels who used statins during the study, had less than half the risk of developing AD than participants with higher TC levels who did not use statins (HR=.402, p=.095, 95% CI: .138, 1.173). If the protective effects of statins can be further validated, these findings suggest that their use may delay or prevent AD onset in vulnerable populations. PMID- 17353097 TI - Detection of Cd(II) using antibody-modified microcantilever sensors. AB - This work demonstrated the feasibility of detecting divalent Cd(II) ions using antibody-modified microcantilever (MCL) sensors. Different surface modification methods were compared and multilayer approach was found superior than others for MCL surface modifications for antibody-based Cd(II) sensor development. When the Cd(II)-EDTA complex sample is injected into the fluid cell where the MCL is held, the MCL bends upon the recognition of the Cd(II) complex by the antibody on the surface of the MCL. Control experiments showed that complex that does not contain Cd(II) did not cause any bending of the MCL. The detection limit of the sensor was approximately 10(-9) M. The reaction rate analysis indicated that Langmuir adsorption model is appropriate to describe the absorption of Cd(II)-EDTA-BSA on the antibody-covered MCL surface. PMID- 17353098 TI - Dynamics of anemia progression and recovery in Babesia bigemina infection is unrelated to initiating parasite burden. AB - To be informative, immunization-and-challenge experiments in support of vaccine development rely on host responses that enable distinctions to be made in the responses of immunized and non-immunized animals to infectious challenge. It is therefore important that animals be challenged with standardized infectious doses that allow such distinctions to be made. We report here the results of a challenge titration experiment in which cattle were challenged with Babesia bigemina, at dosages ranging over six orders of magnitude. No significant dose dependent differences were observed in the maximum fever attained, duration of fever, minimum hematocrit reached, kinetics with which anemia developed or was resolved, or animal weight gain. Significant differences were noted only in the length of time post-infection required to initiate fever, reach maximum fever, and attain maximum reduction in hematocrit. These results suggest that, in the absence of further supporting evidence, it is not possible to conclude any direct anti-parasite effects from reductions in maximum fever or hematocrit drop during B. bigemina immunization-and-challenge experiments. However, lengthening of the time to reduction in hematocrit may be a useful indicator of overt suppression of the challenge inoculum. PMID- 17353099 TI - How reinforcer type affects choice in economic games. AB - Behavioral economists stress that experiments on judgment and decision-making using economic games should be played with real money if the results are to have generality. Behavior analysts have sometimes disputed this contention and have reported results in which hypothetical rewards and real money have produced comparable outcomes. We review studies that have compared hypothetical and real money and discuss the results of two relevant experiments. In the first, using the Sharing Game developed in our laboratory, subjects' choices differed markedly depending on whether the rewards were real or hypothetical. In the second, using the Ultimatum and Dictator Games, we again found sharp differences between real and hypothetical rewards. However, this study also showed that time off from a tedious task could serve as a reinforcer every bit as potent as money. In addition to their empirical and theoretical contributions, these studies make the methodological point that meaningful studies may be conducted with economic games without spending money: time off from a tedious task can serve as a powerful reward. PMID- 17353100 TI - Non-contingent positive and negative reinforcement schedules of superstitious behaviors. AB - The role of schedules of reinforcement on the development of superstitious conditioning was investigated in a college age population. Participants were randomly assigned to one of eight operant schedules and instructed to remove (escape), prevent and/or remove (avoidance and escape) or produce (positive) the appearance of a computer generated stimulus using a response pad. Results from the experiment indicate that concomitant (escape and avoidance) schedules of reinforcement are most effective in facilitating acquisition of superstitious behavior as measured by self-reports of participants. PMID- 17353101 TI - Bupropion SR for the treatment of smokeless tobacco use. AB - BACKGROUND: No pharmacotherapies have been shown to increase long-term (> or = 6 months) tobacco abstinence rates among smokeless tobacco (ST) users. Bupropion SR has demonstrated potential efficacy for ST users in pilot studies. We conducted a multicenter, randomized, double-blind, placebo-controlled, clinical trial to assess the efficacy and safety of bupropion SR for tobacco abstinence among ST users. METHODS: Adult ST users were randomized to bupropion SR titrated to 150 mg twice daily (N=113) or placebo (N=112) for 12 weeks plus behavioral intervention. The primary endpoint was the 7-day point-prevalence tobacco abstinence rate at week 12. Secondary outcomes included prolonged and continuous tobacco abstinence rates, craving and nicotine withdrawal, and weight gain. RESULTS: The 7-day point prevalence tobacco abstinence rates did not differ between bupropion SR and placebo at the end treatment (53.1% versus 46.4%; odds ratio (OR) 1.3; p=0.301). The 7-day point-prevalence abstinence did not differ at weeks 24 and 52. The prolonged and continuous tobacco abstinence rates did not differ at weeks 12, 24, and 52. A time-by-treatment interaction was observed in craving over time with greater decreases in the bupropion SR group. At 12 weeks, the mean (+/-S.D.) weight change from baseline among abstinent subjects was an increase of 1.7 (+/ 2.9)kg for the bupropion SR group compared to 3.2 (+/-2.7)kg for placebo (p=0.005). CONCLUSIONS: Bupropion SR did not significantly increase tobacco abstinence rates among ST users, but it significantly decreased craving and weight gain over the treatment period. PMID- 17353102 TI - The age-dependent expression of the F18+ E. coli receptor on porcine gut epithelial cells is positively correlated with the presence of histo-blood group antigens. AB - F18(+)Escherichia coli have the ability to colonize the gut and cause oedema disease or post-weaning diarrhoea by adhering to specific F18 receptors (F18R) on the porcine epithelium. Although it is well established that a DNA polymorphism on base pair 307 of the FUT1 gene, encoding an alpha(1,2)fucosyltransferase, accounts for the F18R phenotype, the F18R nature is not elucidated yet. The aim of the present study was to investigate the correlation between the presence of H 2 histo-blood group antigens (HBGAs) or its derivative A-2 HBGAs on the porcine gut epithelium and F18(+)E. coli adherence. A significant positive correlation was found between expression of both the H-2 (r=0.586, P<0.01) and A-2 (r=0.775, P<0.01) HBGAs and F18(+)E. coli adherence after examination of 74 pigs aged from 0 to 23 weeks. The majority of the genetically resistant pigs (FUT1M307(A/A)) showed no HBGA expression (91.7%) and no F18(+)E. coli adherence (83.3%). In addition, it was found that F18R expression levels rise with increasing age during the first 3 weeks after birth and that F18R expression is maintained in older pigs (3-23 weeks old). Taken together, these data suggest that, apart from H-2 HBGAs, A-2 HBGAs might be involved in F18(+)E. coli adherence. PMID- 17353103 TI - Experimental persistent infection with bovine viral diarrhea virus in white tailed deer. AB - Bovine viral diarrhea virus (BVDV) infections cause substantial economic losses to the cattle industries. Persistently infected (PI) cattle are the most important reservoir for BVDV. White-tailed deer (Odocoileus virginianus) are the most abundant species of wild ruminants in the United States and contact between cattle and deer is common. If the outcome of fetal infection of white-tailed deer is similar to cattle, PI white-tailed deer may pose a threat to BVDV control programs. The objective of this study was to determine if experimental infection of pregnant white-tailed deer with BVDV would result in the birth of PI offspring. Nine female and one male white-tailed deer were captured and housed at a captive deer isolation facility. After natural mating had occurred, all does were inoculated intranasally at approximately 50 days of pregnancy with 10(6) CCID(50) each of a BVDV 1 (BJ) and BVDV 2 (PA131) strain. Although no clinical signs of BVDV infection were observed or abortions detected, only one pregnancy advanced to term. On day 167 post-inoculation, one doe delivered a live fawn and a mummified fetus. The fawn was translocated to an isolation facility to be hand raised. The fawn was determined to be PI with BVDV 2 by serial virus isolation from serum and white blood cells, immunohistochemistry on skin biopsy, and RT PCR. This is the first report of persistent infection of white-tailed deer with BVDV. Further research is needed to assess the impact of PI white-tailed deer on BVDV control programs in cattle. PMID- 17353104 TI - Two-tone distortion at different longitudinal locations on the basilar membrane. AB - When listening to two tones at frequency f1 and f2 (f2>f1), one can hear pitches not only at f1 and f2 but also at distortion frequencies f2-f1, (n+1)f1-nf2, and (n+1)f2-nf1 (n=1,2,3...). Such two-tone distortion products (DPs) also can be measured in the ear canal using a sensitive microphone. These ear-generated sounds are called otoacoustic emissions (OAEs). In spite of the common applications of OAEs, the mechanisms by which these emissions travel out of the cochlea remain unclear. In a recent study, the basilar membrane (BM) vibration at 2f1-f2 was measured as a function of the longitudinal location, using a scanning laser interferometer. The data indicated a forward traveling wave and no measurable backward wave. However, this study had a relatively high noise floor and high stimulus intensity. In the current study, the noise floor of the BM measurement was significantly decreased by using reflective beads on the BM, and the vibration was measured at relatively low intensities at more than one longitudinal location. The results show that the DP phase at a basal location leads the phase at an apical location. The data indicate that the emission travels along the BM from base to apex as a forward traveling wave, and no backward traveling wave was detected under the current experimental conditions. PMID- 17353105 TI - Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph nodes, and spleen on collagen-induced arthritis in mice. AB - Chelidonium majus L. has multiple applications in Korean traditional medicine because of its anti-tumoral, cytotoxic, anti-inflammatory and anti-microbial activities and has long been known to have anti-inflammatory effects. However, no study on the anti-arthritic activity of Chelidonium majus has been reported in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Cytokine production and gene expression were assessed during CIA (collagen-induced arthritis) model mice in knee joint, lymph node (LN), and spleen, using ELISA and competitive RT-PCR. DBA/1J mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with CME orally at 400, 40mg/kg once a day for 4 weeks. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Administration of CME significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IL-6 in spleen and lymph node. The erosion of cartilage was dramatically reduced in mouse knees after treatment with CME. In conclusion, our results demonstrates that CME significantly suppressed the progression of CIA and that this action was characterized by the decreased production of TNF-alpha, IL-6, IFN-gamma, B cells, gammadelta T cells (in spleen) and increased proportion of CD4+CD25+ regulatory T cells in vivo. In the serum of CME-treated mice, the levels of IgG and IgM RA factor were decreased. PMID- 17353106 TI - The Achilles tendon as a DNA source for STR typing of highly decayed corpses. AB - Forensic criminal casework often involves DNA profiling of human postmortem tissues, whereas degradational processes can affect PCR-based Short Tandem Repeat (STR) analysis. Degradation of DNA is observed to vary among different tissues and with time. Therefore, the stability of DNA in Achilles tendon samples is compared to that in muscle and kidney specimens with a variety of postmortem histories. Tissue samples from 28 autopsy cases, including 15 decomposed corpses and a control group of 13 nondecayed corpses were analysed. DNA was isolated using the All-tissue DNA Kit (GEN-IAL, Troisdorf, Germany), quantified by spectrophotometric measurement, amplified by the multiplex PCR genRES MPX-2 (Serac, Bad Homburg, Germany), and analysed on the ABI PRISM 310 Genetic Analyzer (Applied Biosystems, Darmstadt, Germany). Quantitative analysis of nondecomposed tissues revealed that the recovery of DNA was highest in kidney followed by muscle, whereas Achilles tendon tissue was the poorest source of isolated DNA. Only small amounts of DNA were present in both kidney and muscle samples from decomposed corpses. However, from decayed Achilles tendon samples twice as much DNA as from nondecayed samples could be isolated on average. These results suggest DNA to be better protected in Achilles tendons. Moreover, postmortem changes in Achilles tendons may even improve DNA isolation. PMID- 17353107 TI - The affect of tissue depth variation on craniofacial reconstructions. AB - We examined the affect of tissue depth variation on the reconstruction of facial form, through the application of the American method, utilizing published tissue depth measurements for emaciated, normal, and obese faces. In this preliminary study, three reconstructions were created on reproductions of the same skull for each set of tissue depth measurements. The resulting morphological variation was measured quantitatively using the anthropometric craniofacial variability index (CVI). This method employs 16 standard craniofacial anthropometric measurements and the results reflect "pattern variation" or facial harmony. We report no appreciable variation in the quantitative measure of the pattern facial form obtained from the three different sets of tissue depths. Facial similarity was assessed qualitatively utilizing surveys of photographs of the three reconstructions. Surveys indicated that subjects frequently perceived the reconstructions as representing different individuals. This disagreement indicates that size of the face may blind observers to similarities in facial form. This research is significant because it illustrates the confounding effect that normal human variation contributes in the successful recognition of individuals from a representational three-dimensional facial reconstruction. Research results suggest that successful identification could be increased if multiple reconstructions were created which reflect a wide range of possible outcomes for facial form. The creation of multiple facial images, from a single skull, will be facilitated as computerized versions of facial reconstruction are further developed and refined. PMID- 17353108 TI - Belarusian population genetic database for 15 autosomal STR loci. AB - Allele frequencies of 15 short tandem repeat loci included in the AmpFlSTR Identifiler kit (Applied Biosystems) were obtained from a sample set of unrelated individuals living in Belarus (n=176). For all loci, no deviation from Hardy Weinberg equilibrium was found. Results were compared with data available for the Belarusian minority residing in northeastern Poland and for other Slavic populations. Statistically significant differences were observed between Belarusians and all compared populations. The values of heterozygosity, polymorphic information content (PIC), power of discrimination (PD), power of exclusion (PE), paternity index (PI) and matching probability (pM) were calculated. PMID- 17353109 TI - MRI findings in spinal subdural and epidural hematomas. AB - BACKGROUND: Spinal hematomas are rare entities that can be the cause of an acute spinal cord compression syndrome. Therefore, an early diagnosis is of great importance. PATIENTS AND METHODS: From 2001 to 2005 seven patients with intense back pain and/or acute progressive neurological deficit were studied via 1.5 T MRI (in axial and sagittal T1- and T2-weighted sequences). Follow-up MRI was obtained in six patients. RESULTS: Four patients showed the MRI features of a hyperacute spinal hematoma (two spinal subdural hematoma [SSH] and two spinal epidural hematoma [SEH]), isointense to the spinal cord on T1- and hyperintense on T2-weighted sequences. One patient had an early subacute SEH manifest as heterogeneous signal intensity with areas of high signal intensity on T1- and T2 weighted images. Another patient had a late subacute SSH with high signal intensity on T1- and T2-weighted sequences. The final patient had a SEH in the late chronic phase being hypointense on T1- and T2-weighted sequences. DISCUSSION: MRI is valuable in diagnosing the presence, location and extent of spinal hematomas. Hyperacute spinal hematoma and the differentiation between SSH and SEH are particular diagnostic challenges. In addition, MRI is an important tool in the follow-up in patients with conservative treatment. PMID- 17353110 TI - Focal nodular hyperplasia: spoke-wheel arterial pattern and other signs on dynamic contrast-enhanced ultrasonography. AB - OBJECTIVE: To evaluate the prevalence of spoke-wheel pattern and typical symptoms of focal nodular hyperplasia (FNH) by means of dynamic contrast-enhanced ultrasonography (CEUS) in relation to lesion size. METHODS: Twenty-eight patients were included in the trial, in whom, based on the CEUS, we raised suspicion of hypervascularized liver lesion; there were 30 lesions altogether. The final diagnosis of FNH was verified by means of CT, MRI or lesion biopsy. Majority of patients (26) were females, compared to 2 male, with average age of 33.3 years. Average lesion size was 45.6 mm. Besides the ultrasound examination, we used also "blood pool" ultrasound contrast agent of second generation, sulphur hexafluoride (BR1); we evaluated enhancement of the lesion until the late stage-within 5 min from application. RESULTS: In lesions larger than 3 cm (n=20), stellate vascular enhancement was found in 19 cases (95.0%) early in arterial phase. As for lesions smaller than 3 cm (n=10), spoke-wheel pattern was observed only in 3 cases (30%) and lesions smaller than 2 cm practically did not show this phenomenon at all (n=1; 17%). Generally, symptom of spoke-wheel pattern was observed in 22 cases, i.e. in 73.3%. In total, central scar was present in 63.3% (n=19) of cases. In lesions larger than 3 cm, it was present in 85.0% (n=17), in lesions smaller than 3 cm in 20% (n=2). CONCLUSION: Contrast-enhanced ultrasonography can be the final diagnostic method for FNH larger than 3 cm which has typical spoke-wheel vessel structure on CEUS. If this phenomenon is not present and the central scar is not visible, specific diagnosis of FNH cannot be based solely on CEUS findings. PMID- 17353111 TI - Comparative analysis of cytolethal distending toxin (cdt) genes among Campylobacter jejuni, C. coli and C. fetus strains. AB - The cytolethal distending toxin (cdt) gene clusters of Campylobacter coli strain Co1-243 and C. fetus strain Col-187 were cloned and sequenced to understand the importance of Cdt as a virulence factor. The cdt genes of C. coli and C. fetus consist of three closely linked genes termed cdtA, cdtB, cdtC whose sizes are 774, 801, and 570 bp, and 702, 798, and 546 bp, respectively. The homologies of each subunit of cdt genes between C. jejuni and C. coli, C. jejuni and C. fetus, or C. coli and C. fetus are 59.6%, 40.3%, or 46.5% for cdtA, 70.2%, 62.4%, or 61.3% for cdtB, 61.3%, 52.3%, or 50.1% for cdtC, respectively. Colony hybridization assay revealed that the genes homologous to the cdtABC gene were distributed in all 27, 19, 20 strains of C. jejuni, C. coli, and C. fetus, respectively, isolated from patients and animals in species-specific manner. Furthermore, nucleotide sequence of the cdt operon, including flanking region, of 10 strains of each species indicated that though the size of the cdtB gene was conserved in each species, those of cdtA and cdtC genes varied particularly among C. coli strains. Amino acid residues demonstrated to be important for toxin activity in CdtB, corresponding to H152, D185, D222, D258, H259 in Cj-CdtB, were also conserved in Cc-CdtB and Cf-CdtB. The cdt gene cluster was located in different sites among different species but in the same site of genomes of the same species. Cdt activity produced by C. jejuni and C. fetus varied among strains, however, any C. coli strains exhibited Cdt activity on HeLa cells. These data indicate that the cdt gene may have a potential for virulence factor at least in C. jejuni and C. fetus. PMID- 17353112 TI - Two-dimensional electrophoresis analyses of atopic dermatitis and the chances to detect new candidate proteins by the variations in immobilized pH gradient strips. AB - BACKGROUND: Proteomic approaches, one of the high-throughput technologies, have been used to search for the proteins that are abnormally expressed in human diseases. The atopic dermatitis (AD)-associated genes or proteins are gradually being reported. OBJECTIVE: In accordance with recent reports, we conducted the serial proteomic studies to compare with the protein expression level and to find a critical protein associated with AD. METHODS: We applied two-dimensional electrophoresis (2-DE) coupled with MADI-TOF as well as LC-MS/MS to detect dysregulated protein in the AD proteome obtained from the patient-derived primary cells. Real-time PCR was also conducted to compare with the proteomic results in the transcriptional level. RESULTS: We successfully detected new AD-associated proteins in the AD-derived fibroblasts 2D-PAGE studies due to the IPG strip variations after conducting MALDI-TOF mass spectrometry and identification of the proteins. From the real-time PCR quantifications, we found that the altered expression of caldesmon 1 isoform 5, nucleophosmin 1, esterase D and chloride intracellular channel 4 were well matched both at the transcriptional and translational levels, and this suggested that these proteins may have important involvement with the pathogenesis of AD. CONCLUSION: By simply repeating the trials with changing the commercial strips with different lot numbers in the 2D PAGE analysis, this provided us with new finding in the AD-derived samples. This approach we used may increase the chances of finding new candidate proteins in the clinical samples and it may also be applicable for proteomic studies of other diseases. PMID- 17353113 TI - Leishmania spp.: proficiency of drug-resistant parasites. AB - Leishmaniasis is a disease caused by at least 17 different species of protozoan Leishmania parasites and currently affects around 12 million people living mostly in tropical and subtropical areas. Failure to treat leishmaniasis successfully is often due to drug resistance. However, there are no cellular and molecular markers of chemoresistance against leishmanicidal drugs and the only reliable method for monitoring resistance of individual isolates is the in vitro amastigote/macrophage model. It is thus necessary to find cellular and molecular markers that can be used systematically to identify the drug-resistant phenotype of the infecting parasites. Until now, whether drug resistance in Leishmania compromises parasite proficiency, e.g. in terms of infectivity or metabolism, has not been systematically evaluated. Therefore, here we examine whether the physiological changes expressed by drug-resistant Leishmania reflect a modification of parasite vitality in drug-resistant compared with drug-sensitive parasites. Finally, the clinical implications of drug resistance in Leishmania are also discussed. PMID- 17353114 TI - The role of antibiotics in asthma. AB - There is increasing evidence that atypical respiratory pathogens such as Chlamydophila pneumoniae and Mycoplasma pneumoniae may contribute to the pathogenesis of both stable asthma and asthma exacerbations. It is postulated that these organisms may contribute to inflammation in the airways possibly by activating inflammatory mechanisms in the respiratory tract. The macrolide class of antibiotics may have a part to play in the management of asthma by exerting anti-inflammatory effects on the chronically inflamed airways in addition to their anti-infective action. The ketolide antibiotics may also have similar properties. This paper discusses the role of these antibiotics in the management of asthma. PMID- 17353115 TI - Identification of a new type of PBX1 partner that contains zinc finger motifs and inhibits the binding of HOXA9-PBX1 to DNA. AB - PBX1 belongs to the TALE-class of homeodomain protein and has a wide functional diversity during development. Indeed, PBX1 is required for haematopoiesis as well as for multiple developmental processes such as skeletal patterning and organogenesis. It has furthermore been shown that PBX1 functions as a HOX cofactor during development. More recent data suggest that PBX1 may act even more broadly by modulating the activity of non-homeodomain transcription factors. To better understand molecular mechanisms triggered by PBX1 during female genital tract development, we searched for additional PBX1 partners that might be involved in this process. Using a two hybrid screen, we identified a new PBX1 interacting protein containing several zinc finger motifs that we called ZFPIP for Zinc Finger PBX1 Interacting Protein. We demonstrated that ZFPIP is expressed in embryonic female genital tract but also in other PBX1 expression domains such as the developing head and the limb buds. We further showed that ZFPIP is able to bind physically and in vivo to PBX1 and moreover, that it prevents the binding of HOXA9/PBX complexes to their consensus DNA site. We suggest that ZFPIP is a new type of PBX1 partner that could participate in PBX1 function during several developmental pathways. PMID- 17353116 TI - Effects of sol-gel processing parameters on the phases and microstructures of HA films. AB - Bioactive hydroxyapatite (HA) films were fabricated by a sol-gel method and triethylphosphate and calcium nitrate were used as the phosphorus and calcium precursors, respectively. The effects of the heat treatment temperature, pH level and substrate materials on the phases and microstructures of HA films were studied by X-ray diffraction (XRD), scanning electronic microscopy (SEM) and electronic probe microanalysis (EPMA) and so on. The results show that all the sol-gel films are composed of the phases of HA, CaO, TiO(2) and CaTiO(3). With increasing the calcining temperature, the crystallinity of the films increases, the structure becomes more compact and changes from granular and lamellar to cellular structure, and the Ca/P ratio increases slightly because of the loss of P in the films. The addition of ammonia (adjusting the pH level to be about 7.5) can increase the HA content in the films, and the difference of substrate materials only has a little influence on the microstructure of the sol-gel films. PMID- 17353117 TI - Quantitative and morphological analysis of biofilm formation on self-assembled monolayers. AB - In spite of intensive studies over the past two decades, the influence of surface properties on bacterial adhesion and biofilm formation remains unclear, particularly on late steps. In order to contribute to the elucidation of this point, we compared the impact of two different substrates on the formation of bacterial biofilm, by analysing bacterial amount and biofilm structure on hydrophilic and hydrophobic surfaces. The surfaces were constituted by NH(2)- and CH(3)-terminated self-assembled monolayers (SAMs) on silicon wafers, allowing to consider only the surface chemistry influence because wafers low roughness. A strain of Escherichia coli K12, able to produce biofilm on abiotic surfaces, was grown with culture durations varying from 4h to 336 h on both types of substrates. The amount of adhered bacteria was determined after detachment by both photometry at 630 nm and direct counting under light microscope, while the spatial distribution of adhered bacteria was observed by fluorescence microscopy. A general view of our results suggests a little influence of the surface chemistry on adherent bacteria amount, but a clear impact on dynamics of biofilm growth as well as on biofilm structure. This work points out how surface chemistry of substrates can influence the bacterial adhesion and the biofilm formation. PMID- 17353118 TI - Effect of HLB of additives on the properties and drug release from the glyceryl monooleate matrices. AB - Glyceryl monooleate (GMO) is an amphiphilic surfactant, which as such can solubilize hydrophilic, lipophilic and amphiphilic drug molecules in its different polarity regions. Addition of additives with different polarities in GMO leads to change in phase behavior and related properties of GMO. Effect of the additives with different hydrophilic lipophilic balance (HLB; 1.5, 3, 4, 5, 7, 10 and 11) in GMO matrices on its phase transformation, rheological properties, mechanical properties, wetting and release behavior was investigated. Polarizing light microscopy showed that the GMO matrices incorporated with lower HLB additive (1.5, 3, 4 and 5) form cubic phase at higher rate while lamellar phase was prominent for matrices with additive of HLB 7, 10 and 11. The diametrical crushing strength and viscosity was decreased with increased HLB of additive. Lower HLB additives enhanced contact angle as compared to plain matrices and high HLB additives induced change in solid-liquid interface from hydrophobic to hydrophilic leading to decline in contact angle. Percent swelling of matrices was increased linearly with increase in HLB of additives. Tensiometric method was used for determination of bioadhesive strength of hydrated matrices and it was observed that matrices with additives of HLB 10 presented highest bioadhesion due to higher rate of hydration and formation of lamellar phase. As the HLB of additives in matrix increased, release was shifted from anomalous (non-Fickian) diffusion and/or partially erosion-controlled release to Fickian diffusion. Initial lag was observed for drug released from matrices with additive of HLB 1.5, 3, 4 and 5. Thus incorporation of the additives of different HLB changed molecular packing, which significantly affected drug release pattern. PMID- 17353119 TI - Effect of sun ginseng methanol extract on lipopolysaccharide-induced liver injury in rats. AB - Sun ginseng (SG) is heat-processed Panax ginseng C.A. Meyer steamed at 120 degrees C, which has ginsenoside-Rg(3), -Rk(1), and -Rg(5) as its main ginsenoside components. The effect of SG on lipopolysaccharide (LPS)-induced liver injury in rats was investigated in this study. Intravenous injection of LPS induced excessive nitric oxide (*NO) generation in serum and increased the hepatic mitochondrial thiobarbituric acid-reactive substance (TBA-RS) level. However, the elevated TBA-RS level was significantly lowered by 15 consecutive days of SG administrations. In addition, up-regulated hepatic inducible nitric oxide synthase and heme oxygenase 1 levels in LPS-treated control rats were significantly lowered and increased, respectively, by 100 mg/kg body weight/day of SG administration. These antioxidant effects were thought to be partially related to the deactivation of nuclear factor-kappaB by SG administration. PMID- 17353120 TI - The herbal medicines Saireito and Boiogito improve the hypertension of pre eclamptic rats induced by Nomega-Nitro-L-arginine methyl ester. AB - The chronic inhibition of nitric oxide (NO) synthesis with N(omega)-Nitro-L arginine methyl ester (L-NAME) induces a pre-eclampsia-like syndrome including hypertension in pregnant rats. We tested the traditional herbal medicines Saireito (SR) and Boiogito (BO), which have been used clinically for the treatment of pre-eclampsia, in this model. L-NAME was infused subcutaneously into pregnant rats from gestational day 14 (G14). SR and BO (both at 1, 2g/kg) were administered by gavage from G14 to G20. Systolic blood pressure was measured on G19. SR and BO (both at 1, 2g/kg) inhibited L-NAME-induced hypertension. SR was effective in both pregnant and non-pregnant rats while BO was effective only in pregnant rats. BO increased blood levels of CGRP and decreased levels of endothelin-1; both are known to play important roles in regulation of blood pressure in pre-eclampsia. SR and BO may be beneficial for the treatment and prevention of hypertension in pre-eclampsia. PMID- 17353121 TI - Interstitial lung disease associated with amyopathic dermatomyositis: review of 18 cases. AB - Interstitial lung disease (ILD) associated with amyopathic dermatomyositis (ADM) is a rare and sometimes fatal condition whose clinical features are not well understood. The goal of this study was to clarify the characteristics of ILD based on its development. Eighteen patients diagnosed with ILD associated with ADM were assigned to 1 of 2 groups: (1) a rapidly progressing group, which included patients who developed abnormal lung findings within 1 month of being diagnosed with ADM (n=9); or (2) a slowly progressing group, which including patients who developed lung findings greater than 1 month after diagnosis of ADM (n=9). Serum creatine phosphokinase and C-reactive protein levels were higher in the rapidly progressing group than in the slowly progressing group. Further, arterial pH was higher and PaO(2)/F(I)O(2) was lower in the rapidly progressing group than in the slowly progressing group. On thoracic high-resolution CT, traction bronchiectasis was present in 4 of the 9 rapidly progressing patients but not in any patients of the slowly progressing group. All 9 slowly progressing patients survived with proper treatment, but only 4 of the 9 rapidly progressing patients survived. In ADM, appropriate investigations are likely required for the early diagnosis of ILD. Our data suggest that ILD associated with ADM can be classified into 2 clinical subtypes based on the time course of pulmonary involvement. Patients with rapid progression in respiratory symptoms should undergo intensive treatment as soon as possible to promote favorable outcomes. PMID- 17353122 TI - Chronic bronchitis and chronic obstructive pulmonary disease. The Finnish Action Programme, interim report. AB - The Finnish National Prevention and Treatment Programme for Chronic Bronchitis and COPD, launched in 1998, has, to date, been running for 6 years (2003). The goals of this action programme were to reduce the incidence of COPD and the number of moderate and severe cases of the disease, and to reduce both the number of days of hospitalisation and treatment costs. A prevalent implementation of over 250 information and training events started. Health centres and pharmacies appointed a person in charge of COPD patients. In order to improve the cooperation between primary and specialised care, two thirds of hospital districts created local COPD treatment chains. The early diagnosis of COPD by spirometric examination was activated during the programme. Number of health centres with available spirometric services increased to 95%. Before the start of the programme, approximately 5-9% of the adult population had COPD. During the whole programme, the proportion of male and female smokers decreased from 30% to 26% and from 20% to 19%, respectively. The total number of hospitalisation periods and days due to COPD decreased by 15% and 18%, respectively. Both the number of pensioners and daily sickness days due to COPD also decreased by 18%. Registered COPD induced deaths remained at their previous levels during the monitoring period, i.e. around 1000 deaths out of 5.2 millions annually. The measures recommended by the programme have been widely introduced but they need to be still more effective. PMID- 17353123 TI - The genetics of bronchial asthma in children. AB - Bronchial asthma is a chronic inflammatory disease based on an inappropriate stimulation of the immune system, for instance by environmental aeroallergens. It is characterised by bronchial hyperreactivity, reversible airway obstruction and mucus overproduction. During the last decades bronchial asthma has become the most common disease of childhood. Accordingly, many epidemiological and genetic studies have dealt with its origin. In fact, hundreds of genome-wide linkage analyses and association studies have identified several chromosomal regions harbouring asthma susceptibility genes like chromosome 2q, 5q, 6q, 11q, 12q and 13q. Also about 100 candidate genes for asthma have been described. However, not all of them have been confirmed in independent studies. Besides the genetic predisposition environmental factors play an important role in the development of allergic diseases. Studies predominantly performed in farmer children have shown that exposure to bacterial endotoxin early in life reduces the risk to develop asthma or atopy later on. Thus, recent studies focussed also on the interaction of genes variants with environmental factors which is summarised under the term genetic epidemiology. Further dissection of asthma genetics and its complex interaction with surrounding factors will hopefully help us in the development of new very specific drugs. In addition, the generation of a genetic risk profile for bronchial asthma should enable us for the first time to take well-directed preventive measurements early in live. PMID- 17353124 TI - GM maize from site-specific recombination technology, what next? AB - The term plant genetic engineering has long conveyed a highly efficient and precise process for the manipulation of plant genomes. For nearly two decades, research on recombinase-based applications has steadily advanced the surgical capabilities of plant genome rearrangements. Once considered interesting laboratory exercises, a first crop plant derived from this type of DNA acrobatics is heading to market. Originally configured for a specific application, to remove a selectable marker, it could be the first of more to come - and not just market free plants. PMID- 17353126 TI - Hyperactivity of the facial nucleus produced by chronic electrical stimulation in rats. AB - OBJECTIVE: There are two hypotheses for the pathogenesis of hemifacial spasm (HFS): abnormal cross-transmission between the facial nerve fibers at a site of vascular compression, and hyperactivity of the facial nucleus. To further elucidate the mechanism of HFS, we established an animal model. We applied chronic electrical stimulation (CES) to the facial nucleus in rats, and clarified functional and morphological changes in the nucleus. METHOD: Under anesthesia, a novel intracranial electrode was stereotactically implanted in the facial nucleus of six rats. CES of the facial nucleus via the implanted electrode was applied for 5 min daily for three weeks (CES animals). Facial electromyograms (EMGs) were recorded at rest and during electrical stimulation to study the excitability of the facial nucleus at 1, 2, and 4 weeks after initiating CES. As control animals, six rats were implanted with intracranial electrodes, but did not undergo CES. Electrophysiological studies of the control animals were performed using the same protocol as in the CES animals. RESULT: Spontaneous abnormal movement of the facial muscle mimicking HFS did not occur. Four weeks after starting CES, one of the six CES animals developed an abnormal EMG response with a latency of 10 ms. No control animals developed such a response. CONCLUSIONS: CES of the facial nucleus can produce an abnormal EMG response very similar to the abnormal muscle response (AMR) characteristic of HFS patients. Kindling-like hyperactivity of the facial nucleus induced by CES is the cause of the AMR, suggesting a pathogenesis of HFS. PMID- 17353125 TI - Foot motion in children shoes: a comparison of barefoot walking with shod walking in conventional and flexible shoes. AB - The increased prevalence for flatfoot and hallux valgus in modern societies may be the consequence of inadequate footwear in childhood. Based on the assumption that barefoot walking represents the best condition for the development of a healthy foot the objective of this study was to monitor the influence of commercial footwear on children's foot motion during walking. Furthermore, an attempt was made to reduce this influence by changing the physical properties of standard footwear. Children's barefoot motion pattern was monitored by a marker based optical 3D-tracking method using a multi-segment foot model. In the study's first stage, barefoot walking was compared to walking with a commercial product. In the second stage it was compared to both, the pattern with the commercial product and with the shoe modified on the basis of the findings of the first stage of the study. Eighteen children (8.2+/-0.7 years old) with no foot deformity and with the same shoe size were recruited for this study. It was found that tibio-talar ROM increased in the commercial shoe (26.6 degrees ) compared to the barefoot condition (22.5 degrees , p=0.001) whereas the medial arch changes for push-off were diminished since the variation in arch length was reduced from 9.9% (barefoot) to 5.9% (shoe, p<0.001). Further, ROM in foot torsion along the long foot axis was reduced from 9.8 degrees (bare) to 4.7 degrees (shoe, p<0.001). These parameters could be improved with more flexible footwear. The present study shows that slimmer and more flexible children's shoes do not change foot motion as much as conventional shoes and therefore should be recommended not only for children in this age but for healthy children in general. PMID- 17353127 TI - The morphology of DNA solution in an open fluidic channel studied by non-contact AFM. AB - The morphologies of pure buffer solution and DNA-containing solution in an open fluidic channel with rectangle cross section (1 microm in width and 150 nm in depth) have been explored using non-contact AFM. A remarkable feature is that a uniform nano-scale trench (approximately 15 nm deep and 14 microm long) on the surface of the DNA solution has been observed. The presence of two neighboring stretched DNA molecules near the solution surface may be responsible for the configuration of the nanotrench. This new phenomenon of partially stretched DNA molecules is likely to be useful for the future designing of fluidic devices, and for the manipulation and study of single DNA molecules. PMID- 17353128 TI - Activation cross sections of the 169Tm(d,2n) reaction for production of the therapeutic radionuclide 169Yb. AB - Activation cross sections of deuteron induced nuclear reactions on (169)Tm were measured up to 20 MeV by using the stacked-foil technique. Special emphasis was on production of the internal radiotherapy related radionuclide (169)Yb. No earlier experimental cross-section data on deuteron induced reactions on (169)Tm were found in the literature. The experimental data were compared with the results of the nuclear model codes ALICE-IPPE and EMPIRE-II. The integral yield of the (169)Tm(d,2n)(169)Yb reaction was deduced over the optimum energy range Ed = 20-->9 MeV. At 3.8 MBq/microA.h the yield is lower than that available from the commonly used (168)Yb(n,gamma) (169)Yb reactor method but on the other hand, it is higher than the yields from the earlier investigated (169)Tm(p,n)(169)Yb and (nat)Er(alpha,x) (169)Yb reactions. PMID- 17353129 TI - Measurement of K X-ray fluorescence cross-sections, fluorescence yields and intensity ratios for some elements in the atomic range 22 0.05). Inflammation parameters such as C-reactive protein (CRP) and polymorphonuclear leucocytes (PMN) were also increased in patients with brain tumor compared to controls (p < 0.05). There was a significant correlation between APRIL and CRP and PMN (p < 0.05). Results from the study suggest that APRIL may play a role in the pathogenesis of brain glioblastoma multiforme. It is possible that anti-APRIL therapy might be useful in this disease. However, this cytokine cannot be regarded as a marker of tumor size or of severity of the clinical condition of patients. PMID- 17353163 TI - IL-27 induces the production of IgG1 by human B cells. AB - It has been reported that IL-27 specifically induces the production of IgG2a by mouse B cells and inhibits IL-4-induced IgG1 synthesis. Here, we show that human naive cord blood expresses a functional IL-27 receptor, consisting of the TCCR and gp130 subunits, although at lower levels as compared to naive and memory splenic B cells. IL-27 does not induce proliferative responses and does not increase IgG1 production by CD19(+)CD27(+) memory B cells. However, it induces a low, but significant production of IgG1 by naive CD19(+)CD27(-)IgD(+)IgG(-) spleen and cord blood B cells, activated via CD40, whereas it has no effect on the production of the other IgG subclasses. In addition, IL-27 induces the differentiation of a population of B cells that express high levels of CD38, in association with a down-regulation of surface IgD expression, and that are surface IgG(+/int), CD20(low), CD27(high), indicating that IL-27 promotes isotype switching and plasma cell differentiation of naive B cells. However, as compared to the effects of IL-21 and IL-10, both switch factors for human IgG1 and IgG3, those of IL-27 are modest and regulate exclusively the production of IgG1. Finally, although IL-27 has no effect on IL-4 and anti-CD40-induced Cepsilon germline promoter activity, it up-regulates IL-4-induced IgE production by naive B cells. These results point to a partial redundancy of switch factors regulating the production of IgG1 in humans, and furthermore indicate the existence of a common regulation of the human IgG1and murine IgG2a isotypes by IL-27. PMID- 17353164 TI - Effects of tumor necrosis factor antagonist treatment on hepatitis C-related immunological abnormalities. AB - BACKGROUND: Chronic hepatitis C infection is frequently associated with a mixed cryoglobulinaemia and circulating auto-antibodies, especially anti-smooth muscle cells (SMA) and anti-liver/kidney/microsome type 1 (LKM-1) anti-tissue antibodies. Treatments with TNF antagonists favour the emergence of auto antibodies, and particularly anti-dsDNA antibodies. OBJECTIVE: To determine the impact of TNF antagonists on hepatitis C-related immune abnormalities. METHODS: We prospectively monitored for 14 weeks, six patients with actively replicating chronic hepatitis C, initiating an anti-TNF treatment for an associated rheumatoid arthritis. RESULTS: Anti-nuclear and anti-dsDNA antibodies were induced in two and three patients, respectively. Treatment had no impact on the production of antibodies against extractable nuclear antigens, and it did not induce anti-tissues antibodies in any patient. Cryoglobulinaemia appeared in 2/6 patients, and it persisted in 2 others. No patient developed any news signs of autoimmunity. HCV viraemia remained unchanged. CONCLUSIONS: Induction of auto antibodies by TNF antagonist treatments does not involve anti-tissues antibodies, even in patients with actively replicating chronic hepatitis C prone to produce anti-SMA and anti-LKM-1 antibodies. In contrast, TNF antagonists may favour emergence of cryoglobulinaemia in such patients. PMID- 17353165 TI - The stroke trial - can we predict clinical outcome of patients with ischemic stroke by measuring soluble cell adhesion molecules (CAM)? AB - BACKGROUND: Several studies have found that an increased concentration of haemostatic or inflammation markers was associated with worse prognosis in vascular disease. The inflammatory components in ischemic stroke are of current interest, and there is some experimental evidence that they may be linked. HYPOTHESIS: The study was performed to determine the association between the neurological clinical outcome and levels of cell adhesion molecules in the first four days of hospitalization in patients with acute ischemic event. METHODS: This prospective, pilot, case-controlled study examined the association between the clinical outcome and inflammatory markers within the first few days of hospitalization. The neurological evaluation was performed using the NIH score on admission and four days later, and levels of cell adhesion molecules were measured by ELISA methods on admission and four days later. RESULTS: Twenty three patients with an acute cerebral event (mean age 71 +/- 15 y, 12 women and 11 men) were examined neurologically on admission and four days later. Among 19 patients who improved, there was a significant decrease in the NIH neurological scale, from 3.8 +/- 3.2 to 1.3 +/- 1.8 (p = 0.01), which was accompanied by a significant decrease in the cell adhesion molecules that were measured (E selectin, ICAM-1 and VCAM-1). Of the four patients who did not improve, their mean clinical NIH score was 10 +/- 4.6 and worsened or remained unchanged after four days of follow-up. In this group, we could not demonstrate a significant change in levels of cell adhesion molecules between days one and four. CONCLUSIONS: Patients who improved clinically within the first four days of hospitalization demonstrated a remarkable inhibition of all three cell adhesion molecules that were measured (E-selectin, ICAM-1, and VCAM-1). Patients who did not improve had more severe cerebral infarcts, a higher NIH score on admission (10 +/- 4.6), and no change was observed in levels of cell adhesion molecules during the follow-up period. Measuring cell adhesion molecule levels may predict objectively the clinical outcome in hospitalized patients with acute ischemic stroke. PMID- 17353166 TI - [Influenza A/H5N1 virus outbreaks and prepardness to avert flu pandemic]. AB - This review emphasizes the need to improve the knowledge of the biology of H5N1 virus, a candidate for causing the next influenza pandemic. In-depth knowledge of mode of infection, mechanisms of pathogenesis and immune response will help in devising an efficient and practical control strategy against this flu virus. We have discussed limitations of currently available vaccines and proposed novel approaches for making better vaccines against H5N1 influenza virus. They include cell-culture system, reverse genetics, adjuvant development. Our review has also underscored the concept of therapeutic vaccine (anti-disease vaccine), which is aimed at diminishing 'cytokine storm' seen in acute respiratory distress syndrome and/or hemophagocytosis. PMID- 17353167 TI - [Clinical spectrum of cobalamin deficiency in Tunisia]. AB - PURPOSE: the aim of this study was to determine the prevalence of cobalamin (vitamin B12) deficiency in different populations of patients with clinical manifestations associated or secondary to cobalamin or folates deficiency and to analyse the demographic, clinical, paraclinical investigations in cobalamin deficient patients in Tunisia. METHODS: it was a prospective (1999-2001) multicenter study of 604 patients divided into four groups. The first group is composed of 478 consecutive patients with anaemia and/or macrocytosis with megaloblastic haemopoiesis on bone marrow examination without myelodyslasic or malignancy signs. The second group is made up of 34 patients with unexplained neurological symptoms without the presence of anaemia. The third group was composed of 82 invidious with isolated psychiatric disorders and the 10 patients with Hashimoto thyroiditis constituted the last group. RESULTS: serum cobalamin level was low in 98 %, 23%, 14% of cases, respectively, in the first three groups. Only one case of patients with Hashimoto thyroiditis has serum cobalamin deficiency. Pernicious anaemia (Biermer's disease) was established by dual isotope schilling examination in 103 patients among a sample of 120 serum cobalamin deficient patients (86%). The median age at presentation was 45.5 years. Severe chronic atrophic gastritis was diagnosed in 97.5% of patients with Biermer's disease. Serum antibodies against intrinsic factor and gastric parietal cells were detected in (42.5%) and (60.6%) patients, respectively; (25.5%) patients had the both types of antibodies. 23.4% patients were positive for antithyroid antibodies. Anti-nuclear antibodies were detected in 3% patients. CONCLUSION: an interesting finding of our study was the high frequency of cobalamin deficiency in Tunisia, particularly in relative young patients. Our patients had classic features of florid cobalamin deficiency (severe haematological manifestations and neuro-psychiatric disorders). The main underlying causes of such deficiencies were Biermer's disease. Subtle clinical manifestations should be recognized and investigated even in young patients at risk. PMID- 17353168 TI - [Evaluation of a telemedicine system for the transmission of morpho/immunological data at the inclusion of patients in a therapeutic trial (Goelams LLC 98)]. AB - The performances of the images digitalization and teletransmission systems make them more and more used. Applied to cellular haematology, they contribute to confrontations of diagnosis mostly within the framework of therapeutic trials. We present one of the first approaches of the use of telehematology for the inclusion of patients in the Goelams Chronic Lymphocytic Leukaemia 98 trial. The advantages were the constitution of a protected data bank, conveniently consultable; expertise on identical documents; facility of the exchanges between experts. We were able to set new standards of images sampling for CLL, solve the semantic divergences, to point out the inter-observer variability for the morphology. The limiting factors were the personal investment of the experts, but mainly the implication of first line morphologists which should benefit from adequate tools to apprehend this system of second reading like a quality control. PMID- 17353169 TI - [Biologic tests for the diagnosis of amniotic fluid embolism]. AB - Amniotic fluid embolism is a rare, unpredictable and often lethal complication of pregnancy and childbirth. Because of its variable presentation, an early biologic test would help to establish the diagnosis. We investigated in maternal serum 4 components of amniotic fluid, i.e., alpha-fetoprotein (AFP), l'insuline like growth factor binding protein-1 (IGFBP-1), fetal fibronectin (fFN) and placental alpha1-microglobulin (PAMG-1). On the 6 cesareans controls involved, none of the makers increased after membranes section. PAMG-1 is unsuitable because its detection is always positive or doubtful even in the baseline. On the 7 cases suspected of amniotic fluid embolism, no detectable increase in any of those markers was noted in 3 cases, which is not in favour of this diagnosis. In the remaining cases, IGFBP-1 and fFN became detectable, confirming histological evidences of amniotic fluid embolism in 2 cases. The follow up of those markers in maternal blood confirmed the suspicion of amniotic fluid embolism at 21 wg in one case of ongoing pregnancy. These preliminary results point out the potential interest to assay maternal serum AFP, IGFBP-1 and fFN to confirm amniotic fluid embolism using rapid laboratory tests. PMID- 17353170 TI - [Multisite validation of CDT measurement by the %CDT TIA and the Tina Quant %CDT kits]. AB - The measurement of CDT (Carbohydrate Deficient Transferrin) is an essential biological tool in the diagnosis and follow-up of alcohol abuse. It is also employed as a marker of abstinence for the restitution of driving licences. However, the precision of measurement, and the between laboratory homogeneity of the results are still discussed. The ion exchange followed by immunodetermination of CDT is available in two products, the Tina Quant %CDT (Roche, Mannheim, Germany) and the %CDT TIA (Bio-Rad, Hercules, United States). This multicentre study was undertaken: 1) to evaluate the analytical characteristics of these kits and the homogeneity of the results from one laboratory to another, independently of the method used, 2) to validate the differences between the proposed normal values of both kits, 3) to study the possibility of using commercial control sera as external quality control. Four analytical systems were included in the study (Roche Modular/Hitachi 717, Beckman Coulter Immage and LX20, Dade Behring BNII). Determinations were carried out on pools of sera, commercial control sera, kit controls, and 30 serums of patients. These latter were also analyzed in capillary electrophoresis in order to establish correlations between the techniques. The calibrations were stable over one 2 weeks period. The repeatability of measurements spread out from 3,1% to 24,7%, for a mean value lower than 10%. The commercial control sera provided reliable results, with values adapted to a routine quality control use. The results of the Bio-Rad applications were lower by approximately 20% than those of the Roche application, which justifies the difference of the normal values (2,6% versus 3%), and an identical classification of the patients in at least 27 of the 30 samples. We conclude that the analytical quality of the compared techniques, even if it could be improved, is sufficient to guarantee a good reliability of the results. An external quality control could be proposed by using the control sera that we tested. PMID- 17353171 TI - [Procalcitonin in invasive candidosis]. AB - The use of reliable and specific diagnosis tools in patients of intensive care unit constitutes the best way to follow up these patients and to take charge of severe infections. It is in the context that the measuring of procalcitonin should be considered in order to prove its role in invasive candidosis. This prospective study included 52 patients from an intensive care unit. Blood samples for serum procalcitonin were drawn on days 1, 3, 5. Our results showed that on the one hand, procalcitonin levels have significantly increased in cases of confirmed and probable candidosis. On the other hand, this parameter has a certain prognosis value. In conclusion, an increase in procalcitonin level does not only imply a bacterial infection but it should also evoke a case of invasive candidosis especially in intensive care units. PMID- 17353172 TI - [Diagnostic strategy of mucopolysaccharidosis type I in Tunisia]. AB - A Tunisian patient affected by mucopolysaccharidosis (MPS) was investigated for a biological analysis (quantitative and qualitative glycosaminoglycans (GAG) screening). We have also done an enzymatic determination of alpha-L-iduronidase activity (IDUA). The most common mutation (p.Gln 70 X, p.Trp 402X and p.Pro 533 Arg) were researched by an enzymatic restriction and sequencing of the IDUA gene. Enzymatic and urinary diagnostics suggested a MPS I phenotype. The patient investigated had the mutation p.Pro 533 Arg in the homozygous status, whereas his parents were heterozygous for this mutation. PMID- 17353173 TI - [Massive haemolysis by Clostridium perfringens: quick diagnosis in a patient with severe sepsis]. AB - Septicaemia by clostridia is a rare but nearly always fatal disease. We report a case of mortal massive haemolysis, with virtually no circulating erythrocytes, in a patient with septicaemia by Clostridium perfringens. The early finding of Clostridium perfringens in the direct Gram stain of patient's peripheral blood allowed a quick diagnosis. PMID- 17353174 TI - [Recommendations for expressing uncertainty of measurement of quantitative results in laboratory medicine]. AB - In laboratory medicine, the quantitative results of examinations are interpreted with regard to reference intervals, clinical decision limits or previous results of a patient, from which it is necessary to inform the clinician about the uncertainty of measurement linked to the value of the result. This document explains the problematic of the expression of the uncertainty of measurement. It proposes recommendations concerning a simple way to evaluate uncertainty of measurement using long term internal quality control data and the value of the uncertainty linked to the method calibration. It approaches the determination of analytical goals and the choice of methods and also the comments accompanying the record of results and a help to their interpretation. PMID- 17353175 TI - The possibility of a valuable resource of circulating DNA for single nucleotide polymorphisms genotyping: the application of a rapid and simple polymerase chain reaction with melting curve analysis for methyltetrahydrofolate reductase polymorphisms. AB - Circulating DNA from plasma is easily stored and is a valuable resource to access genetic information indispensable to modern hematology. The aim of the present project was to evaluate the integrity of circulating DNA and to investigate whether such DNA is practically tolerable for genotyping single nucleotide polymorphisms (SNP) of methyltetrahydrofolate reductase (MTHFR). We first established a protocol combined with polymerase chain reaction (PCR) and melting curve analysis (MCA) based on the different melting temperatures of heteroduplex amplicons. This method was simple and rapid, requiring 3 hours without any complex manipulation, and allowed for a reliable test and diagnostic validity. The median of the circulating DNA density in 240 donors was 33.5 ng/mL. The DNA consisted of fragments with approxiately 100 to 500 base pairs. Such DNA fragments were acceptable for quantifying the housekeeping genes of - globin using a real-time PCR method and also for genotyping the MTHFR SNP using the method of PCR with MCA. Circulating DNA from storage plasma is acceptable for genetic tests, but it is necessary to note the integrity of DNA. PMID- 17353176 TI - Reticulocyte hemoglobin equivalent: an indicator of reduced iron availability in chronic kidney diseases during erythropoietin therapy. AB - Anemia is a common complication of chronic kidney disease (CKD), particularly in dialysis patients. Correction of anemia in CKD patients includes the administration of both recombinant human erythropoietin and intravenous iron. An optimization of iron treatment requires obtaining a target hemoglobin level and avoiding an excessive body-iron overload. The reticulocyte hemoglobin content (CHr) has been shown to be an early indicator of iron-restricted erythropoiesis. The recent European guidelines for anemia treatment in CKD assessed the value for CHr >29 pg/cell as the reticulocyte parameter to evaluate a patient's iron needs. The reticulocyte hemoglobin equivalent (RET-He), recently introduced to determine the forward scatter of fluorescence-labeled reticulocytes, seems to be a sensitive indicator of iron-deficiency anemia. This study evaluates the concordance between the CHr parameter, used as a reference, and the new RET-He in a cohort of 57 dialysis patients referred to the Nephrology Unit of our hospital. All patients received erythropoietin, and iron was administered intravenously to maintain the hemoglobin level between 10 and 12 mg/dL. A total of 285 determinations were performed with both instruments. In the dialysis population, the 95% central range for CHr of 24.8 to 36.3 pg corresponds to a range for RET He of 23.3 to 40.1 pg, with a mean bias of 1.12 pg between the 2 parameters. In comparison with CHr, the value of 30.5 pg for RET-He appeared to be the best cut off point with a very good sensitivity and specificity to determine patients needing iron supplementation. Our study showed an excellent diagnostic efficiency of RET-He to evaluate patients needing iron support and demonstrated a strict correspondence between the classic CHr and the new Ret-He. This correspondence was independent of clinical changes, frequently occurring in dialysis patients. Both parameters could be used soon to guide and monitor iron treatment in dialysis patients. PMID- 17353177 TI - Neutrophil VCS parameters are superior indicators for acute infection. AB - A reliable and cost-effective laboratory method for diagnosing early bacterial infection is needed. The purpose of this study is to compare the sensitivity and specificity of the mean neutrophil volume (MNV) and neutrophil volume distribution width (NDW) parameters with manual band counts, as well as absolute neutrophil count (ANC) and Creactive protein (CRP). We analyzed the clinical history and laboratory data from 242 adult patients with subsequent randomization into 3 groups: patients with no apparent clinical evidence of infection (group 1), localized infection (group 2), and severe infection (group 3). Total white blood cell counts, percentage of neutrophils, ANC, band counts, MNV, and NDW were progressively elevated from group 1 to group 3. There were good correlations between MNV and ANC (P < .05) or band counts (P < .001). Similarly, the NDW correlated well with ANC (P < .001) and band counts (P < .05). Statistical analyses further confirmed that the MNV and NDW were better parameters, with larger areas under the curve than those of CRP, band count, and ANC. The neutrophil VCS parameters, MNV and NDW, have superior sensitivity and specificity compared to manual band count, ANC, and CRP. MNV and NDW are useful indicators in diagnosing acute infectious processes. PMID- 17353178 TI - Karyotypic identification of abnormal clones preceding morphological changes or occurring with no definite morphological features of myelodysplastic syndrome: a preliminary study. AB - The diagnosis of myelodysplastic syndrome (MDS) is difficult to establish based on morphologic features alone because dysplasia may not always be detectable and the presence of dysplasia is not itself evidence of clonal disorder. As a result, the detection of a clonal cytogenetic abnormality has a major role in difficult cases in regard to diagnosis and the recognition of morphological cytogenetic correlates. In an attempt to assess the frequency and characteristic type of abnormal clones when it is not clear whether or not a hematological condition is neoplastic, cytogenetics have been analyzed necessarily in 159 patients with unexplained cytopenia or suspected MDS. We found 14 patients (8.8%) with cytogenetic abnormalities in the absence of concomitant dysplastic features of the marrow at diagnosis. The cytogenetic changes were characteristic of those reported for myeloid malignancies: 3 del(20q), 2 Y chromosome losses, 2 del(5q), 2 11q23 abnormalities, and one each of t(3;5), i(7q), trisomy 8, and del(13q). One case of ring chromosome 4 was also found. A few months later, 3 of these patients showed marrow changes consistent with MDS. Our data demonstrated that a significant proportion of otherwise uncertain diagnoses presented abnormal clones. Long-term follow-up will be required to help determine the malignant potential of these clones. PMID- 17353179 TI - Minimal residual disease testing in acute leukemia by flow cytometry immunophenotyping: prognostic significance. AB - Two main techniques are being used for the detection of minimal residual disease (MRD) in acute leukemia (AL): immunophenotypic analysis and polymerase chain reaction (PCR). In this paper, we analyze the results of assessing MRD by means of flow cytometry (FC) in a group of 93 patients with AL who were prospectively studied and treated in a single institution over a 9-year period. The presence or absence of MRD was established at a cut-off level of 2%, as judged by FC; a single result above this level was considered to define the positivity. The patients were grouped in 4 subsets: (1) acute lymphoblastic leukemia (ALL) patients with MRD (n = 36); (2) acute myeloblastic leukemia (AML) patients with MRD (n = 13); (3) ALL patients without MRD (n = 31); and (4) AML patients without MRD (n = 13). The relapse rates in these groups were 17%, 8%, 0%, and 0%, respectively, whereas the overall 7-year survival was 65%, 69%, 83%, and 98%, respectively. Our results support the usefulness of serially assessing MRD in patients with AL by means of FC; because this method is applicable to all cases of AL, despite being less sensitive than a molecular biology study; it is a good option to follow-up patients and to decide therapeutic and timely interventions. PMID- 17353180 TI - Morphological diagnosis by bone marrow aspirate of toxoplasmosis infection in an HIV-positive patient. AB - An HIV-positive woman receiving antiretroviral therapy developed an opportunistic toxoplasma infection, detected by morphological examination of bone marrow aspirate in the absence of serological positivity. The intracellular presence of Toxoplasma gondii was confirmed by indirect immunofluorescence microscopy, using a polyclonal antitoxoplasma antiserum on marrow smears. This case report confirms the utility of morphological bone marrow examination for the diagnosis of parasitic infections in patients with impaired host defenses. PMID- 17353181 TI - Blastoid mantle cell lymphoma occurring in a patient in complete remission of chronic myelogenous leukemia. AB - The development of a de novo lymphoma in patients affected by chronic myelogenous leukemia (CML) is a rare event. The introduction of new molecular cytogenetic techniques, such as fluorescence in situ hybridization (FISH), allows a correct differential diagnosis between lymphoid blastic crisis and a blastoid variant of mantle cell lymphoma (MCL), which shows an aggressive behavior and some molecular characteristics detectable by cytogenetics and immunohistochemistry. We report a case of a blastoid variant of MCL that developed in a patient with CML who achieved complete cytogenetic and molecular response to imatinib mesylate treatment. PMID- 17353182 TI - Parvovirus B19 infection after plasma exchange for myasthenia gravis. AB - We describe a case of pure red cell aplasia caused by a B19 parvovirus infection in a female myasthenic patient treated with plasma exchange, corticosteroids, and cholinesterase inhibitors. Two weeks after albumin infusion, she developed anemia with an absence of reticulocytes. A bone marrow aspirate was performed, showing a markedly hypoplastic erythroid series with numerous giant pronormoblasts. Anemia with severe reticulocytopenia and morphology of bone marrow suggested a diagnosis of pure erythroblastopenia due to parvovirus B19 infection, which was confirmed by positive immunoglobulin (Ig)M] and IgG anti-B19 virus. The patient successfully responded to IVIG treatment with a complete remission. In this case, we could not confirm whether an albumin-derived infection combined with a concomitant immunocompromised condition due to myasthenia and immunosuppressive treatment was responsible for the disease. Although human B19 DNA content does not reflect infectivity, it is not possible to exclude that blood derivates, such as albumin, clot factors, and immune globulin may be infectious. Actually, blood component B19 infection is still an unresolved problem. Many strategies such as new methods for viral inactivation and discarding positive B19 units may help to increase blood product safety. PMID- 17353183 TI - Reticulocyte counts of Thai vegans compared with nonvegetarians. PMID- 17353184 TI - N-acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark. Environmental Health Perspectives;1979:71-79. PMID- 17353185 TI - Hierarchical classification of functionally equivalent genes in prokaryotes. AB - Functional classification of genes represents a fundamental problem to many biological studies. Most of the existing classification schemes are based on the concepts of homology and orthology, which were originally introduced to study gene evolution but might not be the most appropriate for gene function prediction, particularly at high resolution level. We have recently developed a scheme for hierarchical classification of genes (HCGs) in prokaryotes. In the HCG scheme, the functional equivalence relationships among genes are first assessed through a careful application of both sequence similarity and genomic neighborhood information; and genes are then classified into a hierarchical structure of clusters, where genes in each cluster are functionally equivalent at some resolution level, and the level of resolution goes higher as the clusters become increasingly smaller traveling down the hierarchy. The HCG scheme is validated through comparisons with the taxonomy of the prokaryotic genomes, Clusters of Orthologous Groups (COGs) of genes and the Pfam system. We have applied the HCG scheme to 224 complete prokaryotic genomes, and constructed a HCG database consisting of a forest of 5339 multi-level and 15 770 single-level trees of gene clusters covering approximately 93% of the genes of these 224 genomes. The validation results indicate that the HCG scheme not only captures the key features of the existing classification schemes but also provides a much richer organization of genes which can be used for functional prediction of genes at higher resolution and to help reveal evolutionary trace of the genes. PMID- 17353186 TI - The Src-like adaptor protein 2 regulates colony-stimulating factor-1 receptor signaling and down-regulation. AB - Src-like adaptor protein 2 (SLAP-2) is a hematopoietic adaptor protein previously implicated as a negative regulator of T-cell antigen receptor (TCR)-mediated signaling. SLAP-2 contains an SH3 and an SH2 domain, followed by a unique carboxyl-terminal tail, which is important for c-Cbl binding. Here we describe a novel role for SLAP-2 in regulation of the colony-stimulating factor 1 receptor (CSF-1R), a receptor tyrosine kinase important for growth and differentiation of myeloid cells. SLAP-2 co-immunoprecipitates with c-Cbl and CSF-1R in primary bone marrow-derived macrophages. Using murine myeloid cells expressing CSF-1R (FD-Fms cells), we show that SLAP-2 is tyrosine-phosphorylated upon stimulation with CSF 1 and associates constitutively with both c-Cbl and CSF-1R. In addition, we show that expression of a dominant negative form of SLAP-2 impairs c-Cbl association with the CSF-1R and receptor ubiquitination. Impaired c-Cbl recruitment also correlated with changes in the kinetics of CSF-1R down-regulation and trafficking. CSF-1-mediated differentiation of FD-Fms cells and activation of downstream signaling events was also enhanced in cells stably expressing dominant negative SLAP-2. Together, these results demonstrate that SLAP-2 plays a role in c-Cbl-dependent down-regulation of CSF-1R signaling. PMID- 17353187 TI - Enhanced deacetylation of p53 by the anti-apoptotic protein HSCO in association with histone deacetylase 1. AB - HSCO (hepatoma subtracted-cDNA library clone one, also called ETHE1) was originally identified by its frequent overexpression in hepatocellular carcinomas. HSCO inhibits function of NF-kappaB by binding to RelA and accelerating its export from the nucleus. We show here that HSCO exhibits anti apoptotic activity in cells exposed to DNA-damaging agents by suppressing transcriptional activity of p53. Induction of pro-apoptotic genes, Noxa, Perp, PIG3, and Bax were suppressed in cells over-expressing HSCO. By increasing ubiquitylation and degradation of p53, HSCO reduces p53 protein levels. HSCO specifically associates with histone deacetylase 1 (HDAC1) independently of Mdm2 and facilitates deacetylation of p53 at Lys-373/382 by HDAC1. The metallo-beta lactamase family consensus sequence in HSCO is important for its effect on p53 deacetylation. Co-immunoprecipitation and immunofluorescence studies suggested that HSCO, HDAC1, and p53 form a complex in the nucleus. Thus, HSCO is a cofactor that increases the deacetylase activity of HDAC1 toward p53, leading to suppression of apoptosis. Treatment of hepatocellular carcinomas that retain wild type p53 and overexpress HSCO with anti-HSCO agents might re-establish the p53 response and revert chemoresistance. PMID- 17353188 TI - Reduction of low molecular weight protein-tyrosine phosphatase expression improves hyperglycemia and insulin sensitivity in obese mice. AB - To investigate the role of low molecular weight protein-tyrosine phosphatase (LMW PTP) in glucose metabolism and insulin action, a specific antisense oligonucleotide (ASO) was used to reduce its expression both in vitro and in vivo. Reduction of LMW-PTP expression with the ASO in cultured mouse hepatocytes and in liver and fat tissues of diet-induced obese (DIO) mice and ob/ob mice led to increased phosphorylation and activity of key insulin signaling intermediates, including insulin receptor-beta subunit, phosphatidylinositol 3-kinase, and Akt in response to insulin stimulation. The ASO-treated DIO and ob/ob animals showed improved insulin sensitivity, which was reflected by a lowering of both plasma insulin and glucose levels and improved glucose and insulin tolerance in DIO mice. The treatment did not decrease body weight or increase metabolic rate. These data demonstrate that LMW-PTP is a key negative regulator of insulin action and a potential novel target for the treatment of insulin resistance and type 2 diabetes. PMID- 17353189 TI - Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter. AB - Several acid/base-coupled membrane transporters, such as the electrogenic sodium bicarbonate cotransporter (NBCe1), have been shown to bind to different carbonic anhydrase isoforms to create a "transport metabolon." We have expressed NBCe1 derived from human kidney in oocytes of Xenopus leavis and determined its transport activity by recording the membrane current in voltage clamp, and the cytosolic H(+) and Na(+) concentrations using ion-selective microelectrodes. When carbonic anhydrase isoform II (CAII) had been injected into oocytes, the membrane current and the rate of cytosolic Na(+) rise, indicative for NBCe1 activity, increased significantly with the amount of injected CAII (2-200 ng). The CAII inhibitor ethoxyzolamide reversed the effects of CAII on the NBCe1 activity. Co expressing wild-type CAII or NH(2)-terminal mutant CAII together with NBCe1 provided similar results, whereas co-expressing the catalytically inactive CAII mutant V143Y had no effect on NBCe1 activity. Mass spectrometric analysis and the rate of cytosolic H(+) change following addition of CO(2)/HCO(3)(-) confirmed the catalytic activity of injected and expressed CAII in oocytes. Our results show that the transport capacity of NBCe1 is enhanced by the catalytic activity of CAII, in line with the notion that CAII forms a transport metabolon with NBCe1. PMID- 17353190 TI - Glucokinase thermolability and hepatic regulatory protein binding are essential factors for predicting the blood glucose phenotype of missense mutations. AB - To better understand how glucokinase (GK) missense mutations associated with human glycemic diseases perturb glucose homeostasis, we generated and characterized mice with either an activating (A456V) or inactivating (K414E) mutation in the gk gene. Animals with these mutations exhibited alterations in their blood glucose concentration that were inversely related to the relative activity index of GK. Moreover, the threshold for glucose-stimulated insulin secretion from islets with either the activating or inactivating mutation were left- or right-shifted, respectively. However, we were surprised to find that mice with the activating mutation had markedly reduced amounts of hepatic GK activity. Further studies of bacterially expressed mutant enzymes revealed that GK(A456V) is as stable as the wild type enzyme, whereas GK(K414E) is thermolabile. However, the ability of GK regulatory protein to inhibit GK(A456V) was found to be less than that of the wild type enzyme, a finding consistent with impaired hepatic nuclear localization. Taken together, this study indicates that it is necessary to have knowledge of both thermolability and the interactions of mutant GK enzymes with GK regulatory protein when attempting to predict in vivo glycemic phenotypes based on the measurement of enzyme kinetics. PMID- 17353191 TI - The chloride dependence of the human organic anion transporter 1 (hOAT1) is blunted by mutation of a single amino acid. AB - Organic anion transporter 1 (OAT1) is key for the secretion of organic anions in renal proximal tubules. These organic anions comprise endogenous as well as exogenous compounds including frequently used drugs of various chemical structures. The molecular basis for the polyspecificity of OAT1 is not known. Here we mutated a conserved positively charged arginine residue (Arg(466)) in the 11(th) transmembrane helix of human OAT1. The replacement by the positively charged lysine (R466K) did not impair expression of hOAT1 at the plasma membrane of Xenopus laevis oocytes but decreased the transport of p-aminohippurate (PAH) considerably. Extracellular glutarate inhibited and intracellular glutarate trans stimulated wild type and mutated OAT1, suggesting for the mutant R466K an unimpaired interaction with dicarboxylates. However, when Arg(466) was replaced by the negatively charged aspartate (R466D), glutarate no longer interacted with the mutant. PAH uptake by wild type hOAT1 was stimulated in the presence of chloride, whereas the R466K mutant was chloride-insensitive. Likewise, the uptake of labeled glutarate or ochratoxin A was chloride-dependent in the wild type but not in R466K. Kinetic experiments revealed that chloride did not alter the apparent K(m) for PAH but influenced V(max) in wild type OAT1-expressing oocytes. In R466K mutants the apparent K(m) for PAH was similar to that of the wild type, but V(max) was not changed by chloride removal. We conclude that Arg(466) influences the binding of glutarate, but not interaction with PAH, and interacts with chloride, which is a major determinant in substrate translocation. PMID- 17353192 TI - Transient receptor potential channel A1 is directly gated by calcium ions. AB - Members of the superfamily of transient receptor potential (TRP) channels are proposed to play important roles in sensory physiology. As an excitatory ion channel TRPA1 is robustly activated by pungent irritants in mustard and garlic and is suggested to mediate the inflammatory actions of environmental irritants and proalgesic agents. Here, we demonstrate that, in addition to pungent natural compounds, Ca(2+) directly gates heterologously expressed TRPA1 in whole-cell and excised-patch recordings with an apparent EC(50) of 905 nm. Pharmacological experiments and site-directed mutagenesis indicate that the N-terminal EF-hand calcium-binding domain of the channel is involved in Ca(2+)-dependent activation. Furthermore, we determine Ca(2+) as prerequisite for icilin activity on TRPA1. PMID- 17353193 TI - Generating disulfides in multicellular organisms: emerging roles for a new flavoprotein family. PMID- 17353194 TI - Somatostatin receptors signal through EFA6A-ARF6 to activate phospholipase D in clonal beta-cells. AB - Somatostatin (SS) is a peptide hormone that inhibits insulin secretion in beta cells by activating its G(i/o)-coupled receptors. Our previous work indicated that a betagamma-dimer of G(i/o) coupled to SS receptors can activate phospholipase D1 (PLD1) (Cheng, H., Grodnitzky, J. A., Yibchok-anun, S., Ding, J., and Hsu, W. H. (2005) Mol. Pharmacol. 67, 2162-2172). The aim of the present study was to elucidate the mechanisms underlying SS-induced PLD activation. We demonstrated the presence of ADP-ribosylation factor Arf1 and Arf6 in clonal beta cells, HIT-T15. We also determined that the activation of PLD1 was mediated through Arf6. Overexpression of dominant-negative (dn) Arf6 mutant, Arf6(T27N), and suppression of mRNA levels using siRNA, both abolished SS-induced PLD activation, while overexpression of wild type Arf6 further enhanced this PLD activation. In contrast, overexpression of dn-Arf1 mutant Arf1(T31N) or dn-Arf5 mutant Arf5(T31N) failed to reduce SS-induced PLD activation. These findings suggested that Arf6, but not Arf1 or Arf5, mediates the effect of SS. We further determined the involvement of the Arf6 guanine nucleotide exchange factor (GEF) EFA6A, a GEF previously thought to be found predominantly in the brain, in the activation of PLD1 in HIT-T15 cells. Using Northern and Western blot analyses, both mRNA and protein of EFA6A were found in these cells. Overexpression of dn EFA6A mutant, EFA6A(E242K), and suppression of mRNA levels using siRNA, both abolished SS-induced PLD activation, whereas overexpression of dn-EFA6B mutant, EFA6B(E651K), failed to reduce SS-induced PLD activation. In addition, overexpression of dn-ARNO mutant, ARNO(E156K), another GEF of Arf6, had no effect on SS-induced activation of PLD. Taken together, these results suggest that SS signals through EFA6A to activate Arf6-PLD cascade. PMID- 17353195 TI - Sequence dependence and differential expression of Ggamma5 subunit isoforms of the heterotrimeric G proteins variably processed after prenylation in mammalian cells. AB - Between 1 and 2% of proteins coded for in the human genome, including all G protein gamma subunits, are predicted to be prenylated. Subsequently, prenylated proteins are proteolytically cleaved at the C terminus and carboxymethylated. These reactions are generally obligatory events required for functional expression of prenylated proteins. The biological role of prenyl substrates has made these reactions significant targets for anticancer drug development. Understanding the enzymology of this pathway will be key to success for this strategy. When Ggamma1, -2, -4, -10, -11, -12, and -13 were expressed in HEK293 cells they were completely processed according to the current understanding of the prenylation reaction. In contrast, Ggamma5 was processed to two forms; a minor one, fully processed as predicted, and a major one that was prenylated without further processing. When the Ca(1)a(2)X motif of Ggamma5, CSFL, was exchanged for that of Ggamma2, CAIL, Ggamma5 was completely processed. Conversely, Ggamma2-SFL was incompletely processed. Differential processing of Ggamma5 was found due to the presence of an aromatic amino acid in its Ca(1)a(2)X motif. Retrieving endogenous Ggamma subunits from HEK293 or Neuro-2a cells with FLAG-Gbeta constructs identified multiple Ggamma subunits by mass spectrometry in either cell, but in both cases the most prominent one was Ggamma5 expressed without C-terminal processing after prenylation. This work indicates that post prenylation reactions can generate multiple products determined by the C-terminal Ca(1)a(2)X motif. Within the human genome 10% of predicted prenylated proteins have aromatic amino acids in their Ca(1)a(2)X sequence and would likely generate the prenylation pattern described here. PMID- 17353196 TI - The immunoglobulin heavy chain constant region affects kinetic and thermodynamic parameters of antibody variable region interactions with antigen. AB - A central dogma in immunology is that antibody specificity is a function of the variable (V) region. However serological analysis of IgG(1), IgG(2a), and IgG(2b) switch variants of murine monoclonal antibody (mAb) 3E5 IgG(3) with identical V domains revealed apparent specificity differences for Cryptococcus neoformans glucuronoxylomannan (GXM). Kinetic and thermodynamic binding properties of mAbs 3E5 to a 12-mer peptide mimetic of GXM revealed differences in the affinity of these mAbs for a monovalent ligand, a result that implied that the constant (C) region affects the secondary structure of the antigen binding site, thus accounting for variations in specificity. Structural models of mAbs 3E5 suggested that isotype-related differences in binding resulted from amino acid sequence polymorphisms in the C region. This study implies that isotype switching is another mechanism for generating diversity in antigen binding and that isotype restriction of certain antibody responses may reflect structural constraints imposed by C region on V region binding. Furthermore, isotype affected the polyreactivity of V region identical antibodies, implying a role for C region in determining self-reactivity. PMID- 17353197 TI - Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation. AB - The stress hormone epinephrine is known to elicit multiple systemic effects that include changes in cardiovascular parameters and immune responses. However, information about its direct action on cancer cells is limited. Here we provide evidence that epinephrine reduces sensitivity of cancer cells to apoptosis through interaction with beta(2)-adrenergic receptors. The antiapoptotic mechanism of epinephrine primarily involves phosphorylation and inactivation of the proapoptotic protein BAD by cAMP-dependent protein kinase. Moreover, BAD phosphorylation was observed at epinephrine concentrations found after acute and chronic psychosocial stress. Antiapoptotic signaling by epinephrine could be one of the mechanisms by which stress promotes tumorigenesis and decreases the efficacy of anti-cancer therapies. PMID- 17353198 TI - Oncogenic KRAS activates hedgehog signaling pathway in pancreatic cancer cells. AB - Hedgehog (Hh) signaling is deregulated in multiple human cancers including pancreatic ductal adenocarcinoma (PDA). Because KRAS mutation represents one of the earliest genetic alterations and occurs almost universally in PDA, we hypothesized that oncogenic KRAS promotes pancreatic tumorigenesis in part through activation of the Hh pathway. Here, we report that oncogenic KRAS activates hedgehog signaling in PDA cells, utilizing a downstream effector pathway mediated by RAF/MEK/MAPK but not phosphatidylinositol 3-kinase (PI3K)/AKT. Oncogenic KRAS transformation of human pancreatic ductal epithelial cells increases GLI transcriptional activity, an effect that is inhibited by the MEK-specific inhibitors U0126 and PD98059, but not by the PI3K-specific inhibitor wortmannin. Inactivation of KRAS activity by a small interfering RNA specific for oncogenic KRAS inhibits GLI activity and GLI1 expression in PDA cell lines with activating KRAS mutation; the MEK inhibitors U0126 and PD98059 elicit a similar response. In addition, expression of the constitutively active form of BRAF(E600), but not myr-AKT, blocks the inhibitory effects of KRAS knockdown on Hh signaling. Finally, suppressing GLI activity leads to a selective attenuation of the oncogenic transformation activity of mutant KRAS-expressing PDA cells. These results demonstrate that oncogenic KRAS, through RAF/MEK/MAPK signaling, is directly involved in the activation of the hedgehog pathway in PDA cells and that collaboration between these two signaling pathways may play an important role in PDA progression. PMID- 17353199 TI - Cellular recognition of trimyristoylated peptide or enterobacterial lipopolysaccharide via both TLR2 and TLR4. AB - Evidence for specific and direct bacterial product recognition through toll-like receptors (TLRs) has been emphasized recently. We analyzed lipopeptide analogues and enterobacterial lipopolysaccharide (eLPS) for their potential to activate cells through TLR2 and TLR4. Whereas bacterial protein palmitoylated at its N terminal cysteine and N-terminal peptides derived thereof are known to induce TLR2-mediated cell activation, a synthetic acylhexapeptide mimicking a bacterial lipoprotein subpopulation for which N-terminal trimyristoylation is characteristic (Myr(3)CSK(4)) activated cells not only through TLR2 but also through TLR4. Conversely, highly purified eLPS triggered cell activation through overexpressed TLR2 in the absence of TLR4 expression if CD14 was coexpressed. Accordingly, TLR2(-/-) macrophages prepared upon gene targeting responded to Myr(3)CSK(4) challenge, whereas TLR2(-/-)/TLR4(d/d) cells were unresponsive. Through interferon-gamma (IFNgamma) priming, macrophages lacking expression of functional TLR4 and/or MD-2 acquired sensitivity to eLPS, whereas TLR2/TLR4 double deficient cells did not. Not only TLR2(-/-) mice but also TLR4(-/-) mice were resistant to Myr(3)CSK(4) challenge-induced fatal shock. d-Galactosamine sensitized mice expressing defective TLR4 or lacking TLR4 expression acquired susceptibility to eLPS-driven toxemia upon IFNgamma priming, whereas double deficient mice did not. Immunization toward ovalbumin using Myr(3)CSK(4) as adjuvant was ineffective in TLR2(-/-)/TLR4(-/-) mice yet effective in wild-type, TLR2(-/-), or TLR4(-/-) mice as shown by analysis of ovalbumin-specific serum Ig concentration. A compound such as Myr(3)CSK(4) whose stimulatory activity is mediated by both TLR2 and TLR4 might constitute a preferable adjuvant. On the other hand, simultaneous blockage of both of the two TLRs might effectively inhibit infection-induced pathology. PMID- 17353200 TI - Advances in neuromembrane proteomics: efforts towards a comprehensive analysis of membrane proteins in the brain. AB - Proteomic investigation of normal and diseased brain states has the potential to reveal novel molecular therapeutic and diagnostic targets for a multitude of pathological central nervous system conditions. Due to their unique properties, integral membrane proteins are likely to play a central role in the aetiology of these disorders. These properties, however, have prevented comprehensive analysis of this important class of proteins. Recent advances in sample preparation and proteomic quantification platforms, specifically focused on recovery and enrichment of integral membrane proteins, are discussed. PMID- 17353201 TI - Trends in socio-economic differences in tobacco smoking among German schoolchildren, 1994-2002. AB - BACKGROUND: While the graded relationship between socio-economic status (SES) and risk behaviour in adulthood has been the subject of intense research, far less is known about socio-economic differences in health-related behaviour among adolescents. The purpose of the present study is to examine socio-economic differences in adolescent tobacco use in Germany as well as changes in the relationship between 1994 and 2002. METHODS: Data were obtained from the 'Health Behaviour in School-aged Children' study conducted in the largest federal state of Germany, Northrhine-Westfalia, in 1994, 1998 and 2002. The analysis is based on 11.401 11- to 15-year old students. Socio-economic differences in regular smoking were studied in relation to both parental SES (family affluence) and students own SES (school type). Trends from 1994 to 2002 were analysed for each category of family affluence and school type separately. RESULTS: Family affluence only had a weak effect on regular smoking while for type of school a strong social gradient for smoking was found for both the genders. Trend analyses within the different family affluence and school-type categories showed that smoking has generally increased in all socio-economic groups. The level of socio economic differences remained virtually unchanged in girls and boys in the past 10 years in Germany. CONCLUSIONS: The same relationships of family affluence and school type with smoking have persisted for almost a decade in Germany. Students own SES affects adolescent smoking substantially. Prevention programmes should focus on the school setting in order to tackle current as well as future health inequalities. PMID- 17353203 TI - Pollen, tapetum and orbicule development in Modiolastrum malvifolium (Malvaceae). AB - BACKGROUND AND AIMS: Although orbicular functions are still a matter of debate, they are considered by most authors to be exclusively formed by a secretory tapetum. However, the presence of orbicules on a peritapetal membrane associated with a plasmodial tapetum has been described for Abutilon pictum (Malvaceae) in a previous study. Thus, studies on other species of Malvaceae are necessary to corroborate the presence of such bodies in other members of the family. Pollen and microsporangium development of Modiolastrum malvifolium has been studied in this work. METHODS: Anthers at different stages of development were processed for transmission electron microscopy and light microscopy. Membranes and pollen walls resistant to acetolysis were isolated from whole anthers. KEY RESULTS: Microspore tetrads have a tetrahedral arrangement. Pollen grains are shed at the bicellular stage. The tapetum is invasive, non-syncytial and a peritapetal membrane with orbicules is formed. CONCLUSIONS: This is the first report of the presence of orbicules on a peritapetal membrane in a species with a tapetum of an invasive, non-syncytial type. Taking into consideration all the information on the subject, it can be concluded that the presence of orbicules is not a stable criterion to differentiate between a secretory or plasmodial, or intermediate invasive, non syncytial tapetum. PMID- 17353202 TI - Evidence of divergence with duration of residence in circulatory disease mortality in migrants to Australia. AB - BACKGROUND: Very little is known about how acculturation affects health in different societal settings. Using duration of residence, this study investigates acculturation and circulatory disease mortality among migrants in Australia. METHODS: Data from death records, 1998-2002, and from 2001 Census data were extracted for seven migrant groups [New Zealand; United Kingdom (UK)/Ireland; Germany; Greece; Italy; China/Singapore/Malaysia/Vietnam (East Asia); and India/Sri Lanka (South Asia)] aged 45-64 years. Poisson regression models were fitted to estimate the duration of residence effect (categorized in 5-year bands and also as having arrived 2-16, 17-31 and 32 years ago or more), adjusted for sex, 5-year age group and year of death, then additionally for occupational class and marital status (SES) on relative risks (RR) of CVD mortality. RESULTS: Compared with the Australia-born population, CVD mortality was generally lower in each migrant group. Decreasing mortality with increasing duration of residence was observed for migrants from New Zealand (RR 0.95, 95% Confidence Interval 0.92 0.98, P<0.01, per 5-year increase), Greece (0.90, 0.86-0.94, P<0.01), Italy (0.94, 0.91-0.97, P<0.01) and South Asia (0.95, 0.91-0.99, P<0.01), mainly in older age groups. Trends remained after SES adjustment and also when broader categories of duration of residence were used. CVD mortality among migrants from the UK/Ireland appeared to converge towards those of the Australian-born. CONCLUSIONS: These results show divergence in CVD mortality compared with the Australian rate for New Zealanders, Greeks, Italians and South Asians. Sustained cardio-protective behavioural practices in the Australian setting is a potential explanation. PMID- 17353204 TI - A new method for non-destructive measurement of biomass, growth rates, vertical biomass distribution and dry matter content based on digital image analysis. AB - BACKGROUND AND AIMS: Biomass is an important trait in functional ecology and growth analysis. The typical methods for measuring biomass are destructive. Thus, they do not allow the development of individual plants to be followed and they require many individuals to be cultivated for repeated measurements. Non destructive methods do not have these limitations. Here, a non-destructive method based on digital image analysis is presented, addressing not only above-ground fresh biomass (FBM) and oven-dried biomass (DBM), but also vertical biomass distribution as well as dry matter content (DMC) and growth rates. METHODS: Scaled digital images of the plants silhouettes were taken for 582 individuals of 27 grass species (Poaceae). Above-ground biomass and DMC were measured using destructive methods. With image analysis software Zeiss KS 300, the projected area and the proportion of greenish pixels were calculated, and generalized linear models (GLMs) were developed with destructively measured parameters as dependent variables and parameters derived from image analysis as independent variables. A bootstrap analysis was performed to assess the number of individuals required for re-calibration of the models. KEY RESULTS: The results of the developed models showed no systematic errors compared with traditionally measured values and explained most of their variance (R(2) > or = 0.85 for all models). The presented models can be directly applied to herbaceous grasses without further calibration. Applying the models to other growth forms might require a re calibration which can be based on only 10-20 individuals for FBM or DMC and on 40 50 individuals for DBM. CONCLUSIONS: The methods presented are time and cost effective compared with traditional methods, especially if development or growth rates are to be measured repeatedly. Hence, they offer an alternative way of determining biomass, especially as they are non-destructive and address not only FBM and DBM, but also vertical biomass distribution and DMC. PMID- 17353205 TI - Comparative cryptogam ecology: a review of bryophyte and lichen traits that drive biogeochemistry. AB - BACKGROUND: Recent decades have seen a major surge in the study of interspecific variation in functional traits in comparative plant ecology, as a tool to understanding and predicting ecosystem functions and their responses to environmental change. However, this research has been biased almost exclusively towards vascular plants. Very little is known about the role and applicability of functional traits of non-vascular cryptogams, particularly bryophytes and lichens, with respect to biogeochemical cycling. Yet these organisms are paramount determinants of biogeochemistry in several biomes, particularly cold biomes and tropical rainforests, where they: (1) contribute substantially to above-ground biomass (lichens, bryophytes); (2) host nitrogen-fixing bacteria, providing major soil N input (lichens, bryophytes); (3) control soil chemistry and nutrition through the accumulation of recalcitrant polyphenols (bryophytes) and through their control over soil and vegetation hydrology and temperatures; (4) both promote erosion (rock weathering by lichens) and prevent it (biological crusts in deserts); (5) provide a staple food to mammals such as reindeer (lichens) and arthropodes, with important feedbacks to soils and biota; and (6) both facilitate and compete with vascular plants. APPROACH: Here we review current knowledge about interspecific variation in cryptogam traits with respect to biogeochemical cycling and discuss to what extent traits and measuring protocols needed for bryophytes and lichens correspond with those applied to vascular plants. We also propose and discuss several new or recently introduced traits that may help us understand and predict the control of cryptogams over several aspects of the biogeochemistry of ecosystems. CONCLUSIONS: Whilst many methodological challenges lie ahead, comparative cryptogam ecology has the potential to meet some of the important challenges of understanding and predicting the biogeochemical and climate consequences of large-scale environmental changes driving shifts in the cryptogam components of vegetation composition. PMID- 17353206 TI - A Race for survival: can Bromus tectorum seeds escape Pyrenophora semeniperda caused mortality by germinating quickly? AB - BACKGROUND AND AIMS: Pathogen-seed interactions may involve a race for seed resources, so that seeds that germinate more quickly, mobilizing reserves, will be more likely to escape seed death than slow-germinating seeds. This race-for survival hypothesis was tested for the North American seed pathogen Pyrenophora semeniperda on seeds of the annual grass Bromus tectorum, an invasive plant in North America. In this species, the seed germination rate varies as a function of dormancy status; dormant seeds germinate slowly if at all, whereas non-dormant seeds germinate quickly. METHODS: Three experimental approaches were utilized: (a) artificial inoculations of mature seeds that varied in primary dormancy status and wounding treatment; (b) naturally inoculated undispersed seeds that varied in primary dormancy status; and (c) naturally inoculated seeds from the carry-over seed bank that varied in degree of secondary dormancy, habitat of origin and seed age. KEY RESULTS: In all three approaches, seeds that germinated slowly were usually killed by the pathogen, whereas seeds that germinated quickly frequently escaped. Pyrenophora semeniperda reduced B. tectorum seed banks. Populations in drier habitats sustained 50 times more seed mortality than a population in a mesic habitat. Older carry-over seeds experienced 30 % more mortality than younger seeds. CONCLUSIONS: Given the dramatic levels of seed death and the ability of this pathogen to reduce seed carry-over, it is intriguing to consider whether P. semeniperda could be used to control B. tectorum through direct reduction of its seed bank. PMID- 17353207 TI - Two measurement methods of leaf dry matter content produce similar results in a broad range of species. AB - BACKGROUND AND AIMS: Leaf dry matter content (LDMC) is widely used as an indicator of plant resource use in plant functional trait databases. Two main methods have been proposed to measure LDMC, which basically differ in the rehydration procedure to which leaves are subjected after harvesting. These are the 'complete rehydration' protocol of Garnier et al. (2001, Functional Ecology 15: 688-695) and the 'partial rehydration' protocol of Vendramini et al. (2002, New Phytologist 154: 147-157). METHODS: To test differences in LDMC due to the use of different methods, LDMC was measured on 51 native and cultivated species representing a wide range of plant families and growth forms from central-western Argentina, following the complete rehydration and partial rehydration protocols. KEY RESULTS AND CONCLUSIONS: The LDMC values obtained by both methods were strongly and positively correlated, clearly showing that LDMC is highly conserved between the two procedures. These trends were not altered by the exclusion of plants with non-laminar leaves. Although the complete rehydration method is the safest to measure LDMC, the partial rehydration procedure produces similar results and is faster. It therefore appears as an acceptable option for those situations in which the complete rehydration method cannot be applied. Two notes of caution are given for cases in which different datasets are compared or combined: (1) the discrepancy between the two rehydration protocols is greatest in the case of high-LDMC (succulent or tender) leaves; (2) the results suggest that, when comparing many studies across unrelated datasets, differences in the measurement protocol may be less important than differences among seasons, years and the quality of local habitats. PMID- 17353208 TI - Interventions to improve water quality for preventing diarrhoea: systematic review and meta-analysis. AB - OBJECTIVE: To assess the effectiveness of interventions to improve the microbial quality of drinking water for preventing diarrhoea. DESIGN: Systematic review. DATA SOURCES: Cochrane Infectious Diseases Group's trials register, CENTRAL, Medline, Embase, LILACS; hand searching; and correspondence with experts and relevant organisations. STUDY SELECTION: Randomised and quasirandomised controlled trials of interventions to improve the microbial quality of drinking water for preventing diarrhoea in adults and in children in settings with endemic disease. DATA EXTRACTION: Allocation concealment, blinding, losses to follow-up, type of intervention, outcome measures, and measures of effect. Pooled effect estimates were calculated within the appropriate subgroups. DATA SYNTHESIS: 33 reports from 21 countries documenting 42 comparisons were included. Variations in design, setting, and type and point of intervention, and variations in defining, assessing, calculating, and reporting outcomes limited the comparability of study results and pooling of results by meta-analysis. In general, interventions to improve the microbial quality of drinking water are effective in preventing diarrhoea. Effectiveness was not conditioned on the presence of improved water supplies or sanitation in the study setting and was not enhanced by combining the intervention with instructions on basic hygiene, a water storage vessel, or improved sanitation or water supplies--other common environmental interventions intended to prevent diarrhoea. CONCLUSION: Interventions to improve water quality are generally effective for preventing diarrhoea in all ages and in under 5s. Significant heterogeneity among the trials suggests that the level of effectiveness may depend on a variety of conditions that research to date cannot fully explain. PMID- 17353209 TI - Level of renal function and serum erythropoietin levels independently predict anaemia post-renal transplantation. AB - BACKGROUND: Post-renal transplant anaemia is a potentially reversible cardiovascular risk factor. Graft function, immunosuppressive agents and inhibition of the renin-angiotensin system have been implicated in its aetiology. The evaluation of erythropoietin (EPO) levels may contribute to understanding the relative contributions of these factors. METHODS: Two-hundred and seven renal transplant recipients attending the Belfast City Hospital were studied. Clinical and laboratory data were extracted from the medical records and laboratory systems. RESULTS: Of the 207 patients (126 male), 47 (22.7%) were found to be anaemic (males, haemoglobin (Hb)<12 g/dl, females Hb<11 g/dl). The anaemic group had a significantly higher mean serum creatinine level (162.8 micromol/l vs 131.0 micromol/l, P<0.001) and lower mean estimated glomerular filtration rate (eGFR) (41.5 ml/min vs 54.9 ml/min, P<0.001) than the non-anaemic group. Individual immunosuppressive regimens were comparable between those with and those without anaemia. Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) administration was not more prevalent in those with anaemia compared with those without (36.2 vs 38.8%, P=0.88). There was a significant inverse correlation between Hb levels and serum EPO levels (R=-0.29, P<0.001), but not between EPO levels and eGFR (R=0.02, P=0.74). Higher EPO levels were predictive of anaemia, independent of eGFR in multivariate analysis. CONCLUSION: Anaemia is common in post-renal transplant patients. The levels of renal function and serum EPO and not immunosuppressive regimens or ACE-I/ARB use, are strong and independent predictors of anaemia. PMID- 17353210 TI - Human herpes virus 8 infection in kidney transplant patients from an area of northwestern Italy (Piemonte region). AB - BACKGROUND: Human herpes virus 8 (HHV-8) infection is associated with Kaposi sarcoma (KS) and other neoplastic and non-neoplastic manifestations. A strong association between HHV-8 and KS has been evidenced in transplant recipients, particularly kidney recipients. METHODS: We have investigated the HHV-8 seroprevalence by an immunoenzymatic assay in 408 patients awaiting kidney transplantation and in the corresponding 356 donors; moreover, we have tested for the presence of HHV-8 DNA by nested PCR in available serum samples of the same graft recipients at 6, 12 and >18 months post-transplantation (overall 156 specimens). Associated factors, such as age, sex, area of residence, potential for HHV-8 transmission via organ transplantation and development of KS were also investigated. RESULTS: Twenty (4.9%) of 408 patients and 7 (1.9%) of 356 donors were seropositive. HHV-8 seropositive patients were on average about 6 years older than seronegative individuals. No difference in prevalence by gender was found. Considering the area of residence of seropositive patients, 4/161 (2.48%) were resident in Piemonte vs 16/247 (6.47%) in other areas of Italy (P = n.s.). During the follow-up post-transplantation, HHV-8 DNA was found only in four patients who were seropositive before transplantation, in three cases the corresponding donor was seronegative, in one the corresponding donor was also seropositive and the recipient developed KS. At >18 months post-transplantation, two patients were HHV-8 DNA positive, both were seronegative pre-transplantation and their corresponding donors were seronegative. CONCLUSIONS: HHV-8 seroprevalence in the Piemonte region seems to be low, also in a population of kidney transplant recipients. Based on our data, it does not seem that the immunosuppressive regimen favours the reactivation of HHV-8. Our results do not suggest the possibility of HHV-8 transmission via organ transplantation. Incidence of KS among HHV-8 seropositive patients was very low. PMID- 17353211 TI - An autistic dimension: a proposed subtype of obsessive-compulsive disorder. AB - This article focuses on the possibility that autism spectrum disorder (ASD: Asperger syndrome, autism and atypical autism) in its milder forms may be clinically important among a substantial proportion of patients with obsessive compulsive disorder (OCD), and discusses OCD subtypes based on this proposition. The hypothesis derives from extensive clinical experience of OCD and ASD, and literature searches on MEDLINE. Neuropsychological deficits are more common in OCD than in panic disorder and depression. Moreover, obsessive-compulsive and schizotypal personality disorders are over-represented in OCD. These may constitute mis-perceived clinical manifestations of ASD. Furthermore, repetitive behaviours and hoarding are common in Asperger syndrome. It is suggested that the comorbidity results in a more severe and treatment resistant form of OCD. OCD with comorbid ASD should be recognized as a valid OCD subtype, analogous to OCD with comorbid tics. An odd personality, with paranoid, schizotypal, avoidant or obsessive-compulsive traits, may indicate these autistic dimensions in OCD patients. PMID- 17353213 TI - Sensory correlations in autism. AB - This study examined the relationship between auditory, visual, touch, and oral sensory dysfunction in autism and their relationship to multisensory dysfunction and severity of autism. The Sensory Profile was completed on 104 persons with a diagnosis of autism, 3 to 56 years of age. Analysis showed a significant correlation between the different processing modalities using total scores. Analysis also showed a significant correlation between processing modalities for both high and low thresholds, with the exception that auditory high threshold processing did not correlate with oral low threshold or touch low threshold processing. Examination of the different age groups suggests that sensory disturbance correlates with severity of autism in children, but not in adolescents and adults. Evidence from this study suggests that: all the main modalities and multisensory processing appear to be affected; sensory processing dysfunction in autism is global in nature; and sensory processing problems need to be considered part of the disorder. PMID- 17353212 TI - Who joins support groups among parents of children with autism? AB - This study identified factors associated with support group participation among families of children with autism. A survey was administered to 1005 caregivers of children with autism in Pennsylvania. Two-thirds of respondents (66.4%) had ever participated in an autism-specific support group. In adjusted analyses, demographic characteristics, including age and sex of the child, ethnicity and parental education and income, were associated with support group participation. Parents of children with self-injurious behavior, sleep problems or severe language deficits were more likely to belong, as were parents whose diagnosing clinician referred them to a support group. The results of this study suggest the importance of clinician referrals to groups, and the need to make groups available to under-served populations. PMID- 17353214 TI - GABA(A) receptor alpha5 subunit as a candidate gene for autism and bipolar disorder: a proposed endophenotype with parent-of-origin and gain-of-function features,with or without oculocutaneous albinism. AB - Our earlier family history studies of individuals with autism found a high incidence of major affective disorder, especially bipolar disorder, and unusual talents or intellectual abilities among family members. We now describe a subgroup of such families, selected from a large clinical experience, illustrating specific features of major affective disorder, special talents or intellectual ability, and familial patterns of trait transmission, with the additional feature of oculocutaneous albinism in some cases. These observations, suggesting parent-of-origin and gain-of-function effects, considered together with recent genetic findings in the literature, suggest a genetic hypothesis possibly unifying disparate observations found in families of individuals with autism. PMID- 17353215 TI - Language development among the siblings of children with autistic spectrum disorder. AB - Language development in 32 preschool siblings (aged 2-6 years) of children with diagnosed autistic spectrum disorder (ASD) was compared with that of a control group of 28 typical preschool children. Groups were matched by siblings' age, gender, maternal educational level and family income. The mean ages of the siblings group and the control group were 4.2 and 4.4 years. Eight of the siblings had delayed language development, of whom three received a diagnosis of developmental language disorder (DLD) and one of ASD. The sibling with ASD and two of those with DLD were excluded; the remaining 29 siblings and the controls were administered the Stanford-Binet IV. Verbal IQs of siblings were not significantly different from the control group. Siblings of children with ASD associated with intellectual impairment ('mental retardation' (MR) in Thailand) had significantly lower verbal IQ scores than siblings of children with ASD but without MR. PMID- 17353216 TI - Restricted object use in young children with autism: definition and construct validity. AB - There are currently no measures of restricted object use in young children with autism. In this study the object play of 27 young children with autism was measured in a semi-structured context to quantify restricted object use. It was hypothesized that children who engaged in less restricted object use would show better responding, joint attention, motor imitation, and intentional communication. Partial correlation coefficients were calculated between restricted object use measured at time 1 and response to joint attention, motor imitation, and coordinated attention to object and person, at time 1 and time 2 (6 months later), controlling for developmental play level. The construct validity of this measure of restricted object use was supported by the statistically significant correlations in the predicted direction of all expected associations. PMID- 17353217 TI - The Childhood Asperger Syndrome Test (CAST): test-retest reliability in a high scoring sample. AB - The Childhood Asperger Syndrome Test (CAST) is a 37-item parental self-completion questionnaire designed to screen for high-functioning autism spectrum conditions in epidemiological research. The CAST has previously demonstrated good accuracy for use as a screening test, with high sensitivity in studies with primary school aged children in mainstream schools. This study aimed to investigate test-retest reliability of the CAST in a high scoring sample. To this end, 73 parents filled in the second CAST (CAST-2) within approximately 2 months of the first administration of the CAST (CAST-1). Agreement above and below the cut-point of 15 was investigated. The kappa statistic for agreement (<15 versus > or =15) was 0.41. It was found that 70 percent (95% CI: 58, 80) of children did not move across the cut-point of 15. The correlation between the two test scores was 0.67 (Spearman's rho). The CAST shows moderate test-retest reliability in a high scoring sample, further evidence that it is a relatively robust screening tool for epidemiological research. PMID- 17353218 TI - Autism and attachment: the Attachment Q-Sort. AB - Children with autism are able to show secure attachment behaviours to their parents/caregivers. Most studies on attachment in children with autism used a (modified) Strange Situation Procedure (SSP) to examine attachment security. An advantage of the Attachment Q-Sort (AQS) over the SSP is that it can be attuned to the secure-base behaviour of children from special populations. In this study experts in the field of autism (both clinicians and researchers: N = 59) defined an AQS criterion sort for children with autism and tested its content validity. Separate criterion sorts were defined for the social subtypes aloof and active but-odd, but the two criterion sorts could be combined into one AQS criterion sort for children with autism. It is concluded that with minor amendments the original Attachment Q-Sort is applicable in observing the attachment behaviour of children with autism. PMID- 17353219 TI - Emergence of RmtB methylase-producing Escherichia coli and Enterobacter cloacae isolates from pigs in China. AB - OBJECTIVES: To investigate the occurrence of 16S rRNA methylases conferring high level resistance to aminoglycosides in Enterobacteriaceae isolated from two pig farms in China. METHODS: Enterobacteriaceae isolated from 151 pig rectal swab samples and 9 environmental samples were screened for the presence of the rmtA, rmtB, armA and rmtC genes by PCR and sequencing. Conjugation experiments were carried out to study the transferability of the 16S rRNA methylase genes. All isolates and their transconjugants were tested for susceptibility to antimicrobial agents. The clonal relatedness of RmtB-producing Escherichia coli was assessed by PFGE with XbaI. RESULTS: Of 152 Enterobacteriaceae isolates recovered from pigs, 49 (32%) were positive for the rmtB gene, including 48 E. coli and a single isolate of Enterobacter cloacae. Of the nine Enterobacteriaceae isolates from environmental samples, no 16S rRNA methylase gene was identified. The 49 rmtB-positive isolates showed resistance to ampicillin, tetracycline and trimethoprim and also carried a bla(TEM) gene. Transfer of the rmtB and bla(TEM) genes by conjugation experiments of all 49 isolates was successful, suggesting that the rmtB-containing plasmids in the E. coli and E. cloacae isolates were self-transmissible. Conjugative transfer frequencies varied from 2.2 x 10(-10) to 1.3 x 10(-6) transconjugants per recipient. The transfer of non-aminoglycoside antimicrobial resistance traits was also observed in most cases. Forty-four rmtB positive E. coli showed 30 different PFGE types. CONCLUSIONS: The rmtB gene was detected on conjugative plasmids of porcine E. coli and E. cloacae isolates. Both horizontal gene transfer and clonal spread were responsible for the dissemination of the rmtB gene. The emergence of 16S rRNA methylases in Enterobacteriaceae isolates is described for the first time in China. This is also the first report of rmtB-positive Enterobacteriaceae among healthy food-producing animals. PMID- 17353220 TI - Activity of faropenem against cephalosporin-resistant Enterobacteriaceae. AB - BACKGROUND: There is a need for new oral agents active against extended-spectrum beta-lactamase (ESBL) producers, as these increasingly cause community-onset infections. We therefore evaluated faropenem, a penem in Phase III development, against recently collected oxyimino-cephalosporin-resistant bacteria. METHODS: We tested 847 consecutive cephalosporin-resistant Enterobacteriaceae collected at 16 centres in South-East England in 2004, 501 of them with CTX-M enzymes; we also tested reference strains and transconjugants with acquired beta-lactamases and various modes of AmpC expression. MICs were determined by the BSAC agar dilution method. RESULTS: Modal MICs of faropenem for Escherichia coli or Klebsiella spp. with CTX-M or non-CTX-M ESBLs or high-level AmpC enzyme were 0.5-1 mg/L, with over 95% of producers susceptible to 90% in CHF patients (299 +/- 283 pmol/mL h; P = 0.004). S-SMase elevation was not different between ischaemic and non-ischaemic CHF and increased stepwise with NYHA class (I, 206 +/ 202; II, 284 +/- 242; III, 306 +/- 212; IV, 440 +/- 665 pmol/mL h; P = 0.003). S SMase correlated with peak VO(2) (R = -0.33, P = 0.0007) and with cytokine activation [tumour necrosis factor-alpha (TNF-alpha) R = 0.22, P = 0.02; sTNF-R1 R = 0.39, P < 0.0001]. S-SMase further correlated with reduced skeletal (quadriceps) muscle strength (R = -0.46, P < 0.0001) as well as impaired peripheral vasodilator capacity (R = -0.34, P = 0.02). In detailed body composition analysis (DEXA scan), S-SMase activity was highest in patients with cardiac cachexia (405 +/- 357 vs. non-cachectic patients: 233 +/- 202 pmol/mL h; P = 0.0007) and related to reduced lean tissue parameters but not to fat tissue parameters. In Cox proportional hazard analysis, elevated SMase related to impaired survival, independent of age, NYHA class, and mean BP (hazard ratio 2.92; 95% confidence interval 1.035-8.24; P = 0.04). CONCLUSION: S-SMase is upregulated in CHF, independent of aetiology. The association of S-SMase with clinical status, tissue amount, functional capacity of skeletal muscle tissue, and vasodilator capacity suggests that S-SMase-mediated signalling may contribute to regulatory processes of CHF pathophysiology. PMID- 17353234 TI - Moderate alcohol consumption in older adults is associated with better cognition and well-being than abstinence. AB - BACKGROUND: There is evidence of a U-shaped association between alcohol consumption and physical health outcomes in older people, such that moderate drinking is associated with better outcomes than abstinence or heavy drinking, but whether moderate drinking in older people is associated with better cognition and mental health than non-drinking has not been explored. OBJECTIVE: To assess the relationship between drinking and cognitive health in middle-aged and older people. DESIGN: Prospective observational study. SETTING/PARTICIPANTS: Six thousand and five individuals aged 50 and over who participated in Wave 1 of the English Longitudinal Study of Ageing (ELSA) and who were not problem drinkers. Exposure and outcome variables: we examined cognitive function, subjective well being, and depressive symptoms, and compared the risks associated with having never drunk alcohol, having quit drinking, and drinking at <1, <2 and >2 drinks per day. RESULTS: For both men and women, better cognition and subjective well being, and fewer depressive symptoms, were associated with moderate levels of alcohol consumption than with never having drunk any. CONCLUSIONS: In middle-aged and older men and women, moderate levels of alcohol consumption are associated with better cognitive health than abstinence. PMID- 17353235 TI - Combined saposin C and D deficiencies in mice lead to a neuronopathic phenotype, glucosylceramide and alpha-hydroxy ceramide accumulation, and altered prosaposin trafficking. AB - Saposins (A, B, C and D) are approximately 80 amino acid stimulators of glycosphingolipid (GSL) hydrolases that derive from a single precursor, prosaposin. In both humans and mice, prosaposin/saposin deficiencies lead to severe neurological deficits. The CD-/- mice with saposin C and D combined deficiencies were produced by introducing genomic point mutations into a critical cysteine in each of these saposins. These mice develop a severe neurological phenotype with ataxia, kyphotic posturing and hind limb paralysis. Relative to prosaposin null mice ( approximately 30 days), CD-/- mice had an extended life span ( approximately 56 days). Loss of Purkinje cells was evident after 6 weeks, and storage bodies were present in neurons of the spinal cord, brain and dorsal root ganglion. Electron microscopy showed well-myelinated fibers and axonal inclusions in the brain and sciatic nerve. Marked accumulations of glucosylceramides and alpha-hydroxy ceramides were present in brain and kidney. Minor storage of lactosylceramide (LacCer) was observed when compared with tissues from the prosaposin null mice, suggesting a compensation in LacCer degradation by saposin B for the saposin C deficiency. Skin fibroblasts and tissues from CD-/- mice showed an increase of intracellular prosaposin, impaired prosaposin secretion, deficiencies of saposins C and D and decreases in saposins A and B. In addition, the deficiency of saposin C in CD-/- mice resulted in cellular decreases of acid beta-glucosidase activity and protein. This CD null mouse model provides a tool to explore the in vivo functional interactions of saposins in GSL metabolism and lysosomal storage diseases, and prosaposin's physiological effects. PMID- 17353236 TI - Comparison of the phosphorylation of 4'-ethynyl 2',3'-dihydro-3'-deoxythymidine with that of other anti-human immunodeficiency virus thymidine analogs. AB - Thymidine analogs, including 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxy 3'-deoxythymidine (D4T), are important antiretroviral agents. To exert antiretroviral activity, these analogs undergo a stepwise phosphorylation intracellularly to the active triphosphate metabolites. We previously reported that 4'-substituted D4T with an ethynyl group (i.e., 4'-ethynyl D4T) increased the anti-human immunodeficiency virus (HIV) activity and was active against multidrug-resistant HIV strains. 4'-Ethynyl D4T is a better substrate for phosphorylation by human thymidine kinase 1 than D4T is. In this report, we first studied the enzymes involved in the phosphorylation of 4'-ethynyl D4T from monophosphate to triphosphate metabolites. The 4'-ethynyl D4TMP is phosphorylated by recombinant human TMP kinase with a K(m) of 19 +/- 4 microM and a k(cat) of 0.007 +/- 0.001 s(-1); the relative efficiency is about 9 and 15% of those of D4TMP and AZTMP, respectively. Several enzymes from crude cellular extracts, including nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, and 3 phosphoglycerate kinase, could phosphorylate 4'-ethynyl D4T-diphosphate. The relative phosphorylation efficiencies of 4'-ethynyl D4TDP were about 3 to 25% of those of D4TDP and were generally similar to those of AZTDP. In T-lymphoid cell lines, there was a preponderant accumulation of 4'-ethynyl D4TMP, suggesting that TMP kinase could be the rate-limiting enzyme in the metabolism of 4'-ethynyl D4T. Although the same enzymes are involved in the stepwise phosphorylation of thymidine analogs, their behaviors in phosphorylating metabolites of 4'-ethynyl D4T are different from those of D4T and AZT. Qualitatively, the metabolism of 4' ethynyl D4T is more similar to that of AZT than to that of its progenitor, D4T. PMID- 17353237 TI - Preclinical testing of candidate topical microbicides for anti-human immunodeficiency virus type 1 activity and tissue toxicity in a human cervical explant culture. AB - A human cervical explant culture was utilized for the preclinical assessment of anti-human immunodeficiency virus type 1 (HIV-1) activity and tissue toxicity of formulated, candidate topical microbicides. Products tested included cellulose acetate 1,2-benzene dicarboxylate (CAP), a carrageenan-based product (PC-515), a naphthalene sulfonate polymer (PRO 2000), a lysine dendrimer (SPL7013), a nonnucleoside reverse transcriptase inhibitor (UC781), and an antimicrobial peptide (D2A21), along with their placebos. Cervical explants were cultured overnight with HIV-1 with or without product, washed, and monitored for signs of HIV-1 infection. HIV-1 infection was determined by p24gag levels in the basolateral medium and by immunohistochemical analysis of the explant. Product toxicity was measured by the MTT [1-(4,5-dimethylthiazol-2-yl)-3,5 diphenylformazan] assay and histology. CAP, PRO 2000, SPL7013, and UC781 consistently prevented HIV-1 infection in all explants tested. PC-515 and D2A21 prevented HIV-1 infection in 50% or fewer of the explants tested. Placebos did not prevent infection in any of the explants tested. With the exception of PRO 2000 (4%), the MTT assay and histological analysis of the other products and placebos showed minimal toxicity to the epithelium and submucosa. Collectively, these data suggest that this culture system can be used for evaluating the safety and efficacy of topical microbicides designed for vaginal use. PMID- 17353238 TI - Exposure-response analyses of tigecycline efficacy in patients with complicated skin and skin-structure infections. AB - Exposure-response analyses were performed for the microbiological and clinical efficacy of tigecycline in the treatment of complicated skin and skin-structure infections, where Staphylococcus aureus and streptococci are the predominant pathogens. A prospective method was developed to create homogeneous patient populations for PK-PD analyses. Evaluable patients from three clinical trials were pooled for analysis. Patients received a tigecycline 100-mg loading dose/50 mg every 12 h or a 50-mg loading dose/25 mg every 12 h. At the test-of-cure visit, microbiologic and clinical responses were evaluated. Patients were prospectively evaluated and classified into cohorts based on baseline pathogens: S. aureus only (cohort 1), monomicrobial S. aureus or streptococci (cohort 2), two gram-positive pathogens (cohort 3), polymicrobial (cohort 4), or other monomicrobial infections (cohort 5). A prospective procedure for combining cohorts was used to increase the sample size. Logistic regression evaluated steady-state 24-h area under the concentration-time curve (AUC(24))/MIC ratio as a predictor of response, and classification and regression tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with pooled cohorts 2 and 3, the focus of these analyses, and included 35 patients with 40 S. aureus and/or streptococcal pathogens. CART analyses identified a significant AUC/MIC breakpoint of 17.9 (P = 0.0001 for microbiological response and P = 0.0376 for clinical response). The continuous AUC/MIC ratio was predictive of microbiological response based on sample size (P = 0.0563). Analysis of all pathogens combined decreased the ability to detect exposure-response relationships. The prospective approach of creating homogeneous populations based on S. aureus and streptococci pathogens was critical for identifying exposure response relationships. PMID- 17353239 TI - Covalent dimer species of beta-defensin Defr1 display potent antimicrobial activity against multidrug-resistant bacterial pathogens. AB - Beta defensins comprise a family of cationic, cysteine-rich antimicrobial peptides, predominantly expressed at epithelial surfaces. Previously we identified a unique five-cysteine defensin-related peptide (Defr1) that, when synthesized, is a mixture of dimeric isoforms and exhibits potent antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa. Here we report that Defr1 displays antimicrobial activity against an extended panel of multidrug resistant nosocomial pathogens for which antimicrobial treatment is limited or nonexistent. Defr1 fractions were collected by high-pressure liquid chromatography and analyzed by gel electrophoresis and mass spectrometry. Antimicrobial activity was initially investigated with the type strain Pseudomonas aeruginosa PAO1. All fractions tested displayed equivalent, potent antimicrobial activity levels comparable with that of the unfractionated Defr1. However, use of an oxidized, monomeric six-cysteine analogue (Defr1 Y5C), or of reduced Defr1, gave diminished antimicrobial activity. These results suggest that the covalent dimer structure of Defr1 is crucial to antimicrobial activity; this hypothesis was confirmed by investigation of a synthetic one-cysteine variant (Defr1-1cys). This gave an activity profile similar to that of synthetic Defr1 but only in an oxidized, dimeric form. Thus, we have shown that covalent, dimeric molecules based on the Defr1 beta-defensin sequence demonstrate antimicrobial activity even in the absence of the canonical cysteine motif. PMID- 17353240 TI - Preclinical safety assessments of UC781 anti-human immunodeficiency virus topical microbicide formulations. AB - The nonnucleoside reverse transcriptase inhibitor UC781 is under development as a potential microbicide to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1). Two gel formulations of UC781 (0.1% and 1.0%) were evaluated in a range of preclinical safety assessments, including systemic absorption analysis following topical application in the pig-tailed macaque models for vaginally and rectally applied topical microbicides. High-sensitivity high-performance liquid chromatography analysis of serum samples showed that no systemic absorption of UC781 was detected after repeated vaginal or rectal application of either product. However, high levels of UC781 were detectable in the cervicovaginal lavage samples up to 6 h after product exposure. Both formulations were safe to the vaginal microenvironment, even with repeated daily use, as evidenced by colposcopy, cytokine analysis, and lack of impact on vaginal microflora. By contrast, rectal application of the 1.0% UC781 formulation caused an increased expression of numerous cytokines not observed after rectal application of the 0.1% UC781 formulation. These results provide additional support for the continued development of UC781 formulations as anti-HIV microbicides. PMID- 17353241 TI - Asiatic acid and corosolic acid enhance the susceptibility of Pseudomonas aeruginosa biofilms to tobramycin. AB - Asiatic acid and corosolic acid are two natural products identified as biofilm inhibitors in a biofilm inhibition assay. We evaluated the activities of these two compounds on Pseudomonas aeruginosa biofilms grown in rotating disk reactors (RDRs) in combination with tobramycin and ciprofloxacin. To determine the ruggedness of our systems, the antibiotic susceptibilities of these biofilms were assessed with tobramycin and ciprofloxacin. The biofilm bacteria produced in the RDR were shown to display remarkable tolerance to 10 mug/ml of ciprofloxacin, thus mimicking the tolerance observed in recalcitrant bacterial infections. These studies further demonstrate that a nonmucoid strain of P. aeruginosa can form a biofilm that tolerates ciprofloxacin at clinically relevant concentrations. Neither asiatic acid nor corosolic acid reduced the viable cell density of P. aeruginosa biofilms. However, both compounds increased the susceptibility of biofilm bacteria to subsequent treatment with tobramycin, suggesting asiatic acid and corosolic acid to be compounds that potentiate the activity of antibiotics. A similar statistical interaction was observed between ciprofloxacin and subsequent treatment with tobramycin. PMID- 17353242 TI - In vitro bactericidal activity of the antiprotozoal drug miltefosine against Streptococcus pneumoniae and other pathogenic streptococci. AB - Miltefosine (hexadecylphosphocholine), the first oral drug against visceral leishmaniasis, triggered pneumococcal autolysis at concentrations higher than 2.5 microM. Bactericidal activity was also observed in cultures of other streptococci, although these failed to undergo lysis. The autolysis elicited by miltefosine can be attributed to triggering of the pneumococcal autolysin LytA. PMID- 17353243 TI - Effect of macrolide usage on emergence of erythromycin-resistant Campylobacter isolates in chickens. AB - In this work we conducted both in vitro and in vivo experiments to examine the development and mechanisms of erythromycin (Ery) resistance in Campylobacter jejuni and Campylobacter coli. In vitro plating revealed that both Campylobacter species had similar but low spontaneous mutation frequencies (3 x 10(-9) to <5.41 x 10(-10)) for Ery resistance. Chickens infected with C. jejuni or C. coli were subjected to single or multiple treatments with medicated water containing tylosin (0.53 g/liter), which transiently reduced the level of Campylobacter colonization but did not select for Ery-resistant (Ery(r)) mutants in the treated birds. However, when tylosin was given to the chickens in feed at a growth promoting dose (0.05 g/kg feed), Ery(r) mutants emerged in the birds after prolonged exposure to the antibiotic. The vast majority of the in vitro- and in vivo-selected Campylobacter mutants with Ery MICs of 8 to 256 microg/ml lacked the known resistance-associated mutations in the 23S rRNA gene, while the highly resistant mutants (Ery MIC > 512 microg/ml) had the A2074G mutation in the 23S rRNA gene. Inactivation of CmeABC, a multidrug efflux pump, dramatically reduced the Ery MIC in all of the examined mutants regardless of the presence of the A2074G mutation. Together, these results reveal distinct features associated with Ery resistance development in Campylobacter, demonstrate the significant role of CmeABC in Ery resistance, and suggest that long-term use of a macrolide as a growth promoter selects for the emergence of Ery(r) Campylobacter in animal reservoirs. PMID- 17353245 TI - Role of homoserine transacetylase as a new target for antifungal agents. AB - Microbial amino acid biosynthesis is a proven yet underexploited target of antibiotics. The biosynthesis of methionine in particular has been shown to be susceptible to small-molecule inhibition in fungi. The first committed step in Met biosynthesis is the acylation of homoserine (Hse) by the enzyme homoserine transacetylase (HTA). We have identified the MET2 gene of Cryptococcus neoformans H99 that encodes HTA (CnHTA) by complementation of an Escherichia coli metA mutant that lacks the gene encoding homoserine transsuccinylase (HTS). We cloned, expressed, and purified CnHTA and determined its steady-state kinetic parameters for the acetylation of L-Hse by acetyl coenzyme A. We next constructed a MET2 mutant in C. neoformans H99 and tested its growth behavior in Met-deficient media, confirming the expected Met auxotrophy. Furthermore, we used this mutant in a mouse inhalation model of infection and determined that MET2 is required for virulence. This makes fungal HTA a viable target for new antibiotic discovery. We screened a 1,000-compound library of small molecules for HTA inhibitors and report the identification of the first inhibitor of fungal HTA. This work validates HTA as an attractive drug-susceptible target for new antifungal agent design. PMID- 17353244 TI - Roxithromycin favorably modifies the initial phase of resistance against infection with macrolide-resistant Streptococcus pneumoniae in a murine pneumonia model. AB - Sub-MIC levels of macrolides down-regulate bacterial virulence factors and suppress inflammatory processes. The ability of macrolides to reduce the production of pneumolysin has been shown to explain the discrepancy between in vitro resistance and outcomes with macrolides against macrolide-resistant Streptococcus pneumoniae. In this study, we determined whether the ability of macrolides to regulate inflammatory processes is beneficial for innate resistance to macrolide-resistant pneumococci in a murine pneumonia model. Among the macrolides tested, only roxithromycin did not affect in vitro pneumococcal virulence factors at sub-MIC levels. Roxithromycin (1.25 to 10 mg/kg of body weight/day) was administered to mice by oral gavage for 3 days before infection with a resistant strain of S. pneumoniae. We evaluated the efficacy of the treatment by determining mouse survival curves and by measuring bacterial burdens and several inflammatory parameters in the airways. Pneumolysin and PspA in infected lungs were examined by Western blot assay. Roxithromycin at doses of > or =5 mg/kg/day increased the median survival time and retarded bacteremia without suppressing the production of pneumolysin and PspA in infected lungs. This treatment reduced matrix metalloproteinase-7 expression and activation and keratinocyte-derived chemokine production in the lungs, while it increased mononuclear cell responses in the lungs, with enhanced bacterial clearance. Concentrations of roxithromycin in plasma and tissues were below the MICs for the inoculated strain during infection. The treatment also reduced inflammatory responses to killed pneumococci in the lungs. These results suggest that the modification by roxithromycin of airway inflammatory responses, including those of matrix metalloproteinase-7 and phagocytes, is beneficial for initial resistance to macrolide-resistant pneumococci. PMID- 17353246 TI - Immunomodulatory effects of fosfomycin in experimental human endotoxemia. AB - To evaluate the effect of fosfomycin on proinflammatory cytokines, a bolus of 2 ng of bacterial lipopolysaccharide/kg of body weight was injected intravenously into healthy volunteers. After 2 h, subjects received 8 g of fosfomycin or placebo in a randomized crossover study design. The resulting concentrations of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-6 expressed as protein and mRNA levels were almost identical with and without fosfomycin. PMID- 17353247 TI - Defining the molecular forces that determine the impact of neomycin on bacterial protein synthesis: importance of the 2'-amino functionality. AB - 2-Deoxystreptamine (2-DOS) aminoglycosides exert their antibiotic actions by binding to the A site of the 16S rRNA and interfering with bacterial protein synthesis. However, the molecular forces that govern the antitranslational activities of aminoglycosides are poorly understood. Here, we describe studies aimed at elucidating these molecular forces. In this connection, we compare the bactericidal, antitranslational, and rRNA binding properties of the 4,5 disubstituted 2-DOS aminoglycoside neomycin (Neo) and a conformationally restricted analog of Neo (CR-Neo) in which the 2'-nitrogen atom is covalently conjugated to the 5''-carbon atom. The bactericidal potency of Neo exceeds that of CR-Neo, with this enhanced antibacterial activity reflecting a correspondingly enhanced antitranslational potency. Time-resolved fluorescence anisotropy studies suggest that the enhanced antitranslational potency of Neo relative to that of CR Neo is due to a greater extent of drug-induced reduction in the mobilities of the nucleotides at positions 1492 and 1493 of the rRNA A site. Buffer- and salt dependent binding studies, coupled with high-resolution structural information, point to electrostatic contacts between the 2'-amino functionality of Neo and the host rRNA as being an important modulator of 1492 and 1493 base mobilities and therefore antitranslational activities. PMID- 17353248 TI - SCO-1, a novel plasmid-mediated class A beta-lactamase with carbenicillinase characteristics from Escherichia coli. AB - A novel class A beta-lactamase (SCO-1) encoded by an 80-kb self-transferable plasmid from Escherichia coli is described. The interaction of SCO-1 with beta lactams was similar to that of the CARB-type enzymes. Also, SCO-1 exhibited a 51% amino acid sequence identity with the RTG subgroup of chromosomal carbenicillinases (RTG-1, CARB-5, and CARB-8). PMID- 17353249 TI - Comparative activities of daptomycin, linezolid, and tigecycline against catheter related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm. AB - In the setting of catheter-related bloodstream infections, intraluminal antibiotic lock therapy could be useful for the salvage of vascular catheters. In this in vitro study, we investigated the efficacies of the newer antibiotics daptomycin, linezolid, and tigecycline, in comparison with those of vancomycin, minocycline, and rifampin, against methicillin-resistant Staphylococcus aureus (MRSA) embedded in biofilm. We also assessed the emergence of MRSA strains resistant to these antibiotics, alone or in combination with rifampin, after 4 hour daily use for catheter lock therapy. Minocycline, daptomycin, and tigecycline were more efficacious in inhibiting MRSA in biofilm than linezolid, vancomycin, and the negative control (P < 0.001) after the first day of exposure to these antibiotics, with minocycline being the most active, followed by daptomycin and then tigecycline, and with vancomycin and linezolid lacking activity, similar to the negative control. After 3 days of 4-hour daily exposures, daptomycin was the fastest in eradicating MRSA from biofilm, followed by minocycline and tigecycline, which were faster than linezolid, rifampin, and vancomycin (P < 0.001). When rifampin was used alone, it was the least effective in eradicating MRSA from biofilm after 5 days of 4-hour daily exposures, as it was associated with the emergence of rifampin-resistant MRSA. However, when rifampin was used in combination with other antibiotics, the combination was significantly effective in eliminating MRSA colonization in biofilm more rapidly than each of the antibiotics alone. In summary, daptomycin, minocycline, and tigecycline should be considered further for antibiotic lock therapy, and rifampin should be considered for enhanced antistaphylococcal activity but not as a single agent. PMID- 17353250 TI - Susceptibility of drug-resistant clinical herpes simplex virus type 1 strains to essential oils of ginger, thyme, hyssop, and sandalwood. AB - Acyclovir-resistant clinical isolates of herpes simplex virus type 1 (HSV-1) were analyzed in vitro for their susceptibilities to essential oils of ginger, thyme, hyssop, and sandalwood. All essential oils exhibited high levels of virucidal activity against acyclovir-sensitive strain KOS and acyclovir-resistant HSV-1 clinical isolates and reduced plaque formation significantly. PMID- 17353251 TI - Single-dose oral amoxicillin or linezolid for prophylaxis of experimental endocarditis due to vancomycin-susceptible and vancomycin-resistant Enterococcus faecalis. AB - Endocarditis prophylaxis following genitourinary or gastrointestinal procedures targets Enterococcus faecalis. Prophylaxis recommendations advocate oral amoxicillin (2 g in the United States and 3 g in the United Kingdom) in moderate risk patients and intravenous amoxicillin (2 g) or vancomycin (1 g) plus gentamicin in high-risk patients. While ampicillin-resistant (or amoxicillin resistant) E. faecalis is still rare, there is a concern that these regimens might fail against vancomycin-resistant and/or aminoglycoside-resistant isolates. The present study tested oral linezolid as an alternative. Rats with catheter induced aortic vegetations were given prophylaxis simulating human pharmacokinetics of oral amoxicillin (2- to 3-g single dose), oral linezolid (600 mg, single or multiple oral doses every 12 h), or intravenous vancomycin (1-g single dose). Rats were then inoculated with the minimum inoculum infecting 90% of the animals (90% infective dose [ID(90)]) or with 10 times the ID(90) of the vancomycin-susceptible E. faecalis strain JH2-2 or the vancomycin-resistant (VanA phenotype) E. faecalis strain UCN41. Amoxicillin was also tested with two additional vancomycin-susceptible E. faecalis strains, 309 and 1209. Animals were sacrificed 3 days later. All the tested bacteria were susceptible to amoxicillin and gentamicin. Single-dose amoxicillin provided 100% protection against all four isolates at both the ID(90) and 10 times the ID(90). In contrast, linezolid required up to four consecutive doses to provide full protection against the vancomycin-resistant isolate. Vancomycin protected only against the vancomycin susceptible strain. The high efficacy of single-dose oral amoxicillin suggests that this regimen could be used for prophylaxis in both moderate-risk and high risk patients without additional aminoglycosides. Linezolid appears to be less reliable, at least against the vancomycin-resistant strain. PMID- 17353252 TI - In Vitro activities of isepamicin, other aminoglycosides, and capreomycin against clinical isolates of rapidly growing mycobacteria in Taiwan. AB - The in vitro activities of isepamicin against 117 Mycobacteria abscessus, 48 Mycobacterium fortuitum, and 20 Mycobacterium chelonae isolates were evaluated by a microdilution test. Isepamicin MIC(90)s were < or =16 microg/ml for the three species. Isepamicin was as active as amikacin and kanamycin and more active than tobramycin, capreomycin, gentamicin, and streptomycin. PMID- 17353253 TI - Anti-MAG/SGPG associated neuropathy does not commonly cause distal nerve temporal dispersion. AB - Patients with anti-myelin associated glycoprotein (anti-MAG) neuropathy have uniform slowing without temporal dispersion, but do usually have disproportionately distal slowing. We evaluated distal compound muscle action potential (CMAP) dispersion in 29 patients with anti-MAG/sulphated glucuronyl paragloboside (SGPG) neuropathy (titres > or = 12,800). Among 138 motor responses, 15% (tibial), 7.3% (peroneal), 10.7% (median) and 13.8% (ulnar) had distal CMAP duration > 9 ms. Disproportionate distal slowing with normal distal CMAP duration in the arms may be useful to differentiate chronic inflammatory demyelinating polyneuropathy from anti-MAG/SGPG associated neuropathy. PMID- 17353254 TI - Termination of complex partial status epilepticus by intravenous levetiracetam. PMID- 17353255 TI - Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. AB - BACKGROUND: Dementia with Lewy bodies (DLB) is a common form of dementia. The presence of Alzheimer's disease (AD) pathology modifies the clinical features of DLB, making it harder to distinguish DLB from AD clinically during life. Clinical diagnostic criteria for DLB applied at presentation can fail to identify up to 50% of cases. Our aim was to determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone. METHODS: A single photon emission computed tomography (SPECT) scan was carried out with a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT; ioflupane) on a group of patients with a clinical diagnosis of DLB or other dementia. An abnormal scan was defined as one in which right and left posterior putamen binding, measured semiquantitatively, was more than 2 SDs below the mean of the controls. RESULTS: Over a 10 year period it was possible to collect 20 patients who had been followed from the time of first assessment and time of scan through to death and subsequent detailed neuropathological autopsy. Eight patients fulfilled neuropathological diagnostic criteria for DLB. Nine patients had AD, mostly with coexisting cerebrovascular disease. Three patients had other diagnoses. The sensitivity of an initial clinical diagnosis of DLB was 75% and specificity was 42%. The sensitivity of the FP-CIT scan for the diagnosis of DLB was 88% and specificity was 100%. CONCLUSION: FP-CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone. PMID- 17353256 TI - Cognitive outcome in adults after bacterial meningitis. AB - OBJECTIVE: To evaluate cognitive outcome in adult survivors of bacterial meningitis. METHODS: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls. RESULTS: Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p<0.001) and tended to be cognitively slower than survivors of meningococcal meningitis (p = 0.08). We found a diffuse pattern of cognitive impairment in which cognitive speed played the most important role. Cognitive performance was not related to time since meningitis; however, there was a positive association between time since meningitis and self-reported physical impairment (p<0.01). The frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar. CONCLUSIONS: Adult survivors of bacterial meningitis are at risk of cognitive impairment, which consists mainly of cognitive slowness. The loss of cognitive speed is stable over time after bacterial meningitis; however, there is a significant improvement in subjective physical impairment in the years after bacterial meningitis. The use of dexamethasone was not associated with cognitive impairment. PMID- 17353257 TI - Myasthenia gravis: a long term follow-up study of Swedish patients with specific reference to thymic histology. AB - BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. The majority of patients show abnormal thymic histology. SETTING: The study was performed at the Myasthenia Gravis Centre, Karolinska University Hospital, and at the Immunological Research Laboratory, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. PATIENTS AND METHODS: Information was collected retrospectively from 1956 and prospectively from 1975 on clinical data, concomitant diseases, concentration of serum acetylcholine receptor antibodies (AChR-abs), immunosuppressive treatment (IS) and response to it, in 537 patients of whom 326 were thymectomised. Follow-up time was 1.5-50 years. RESULTS: Age at onset of MG increased from a median age of 24 years before 1975 to a median age of 61 years after 2000. Thymoma was found in 65, hyperplasia (HPL) in 185 and a normal thymus in 76 patients. The trans-sternal surgical approach for thymectomy was used in 255 patients (78%). In five patients with thymoma, MG appeared after thymectomy. Of 537 patients, 466 (87%) had circulating AChR-abs. IS was given to 300 (56%) patients, mostly those with thymoma (85%). In total, 441 patients (82%) showed an improvement. One-third of patients with HPL, a quarter of those with thymoma, one-fifth of those with a normal thymus and one seventh of those not operated on went into remission. CONCLUSION: The prognosis for the majority of patients with MG is favourable, irrespective of thymic histology. The cause may be the use of immunomodulating therapy. PMID- 17353258 TI - Usefulness of combined fractional anisotropy and apparent diffusion coefficient values for detection of involvement in multiple system atrophy. AB - OBJECTIVE: To determine whether apparent diffusion coefficient (ADC) values and fractional anisotropy (FA) values can detect early pathological involvement in multiple system atrophy (MSA), and be used to differentiate MSA-P (multiple system atrophy if parkinsonian features predominate) from Parkinson's disease (PD). METHODS: We compared ADC and FA values in the pons, cerebellum and putamen of 61 subjects (20 probable MSA patients, 21 age matched PD patients and 20 age matched healthy controls) using a 3.0 T magnetic resonance system. RESULTS: ADC values in the pons, cerebellum and putamen were significantly higher, and FA values lower in MSA than in PD or controls. These differences were prominent in MSA lacking dorsolateral putaminal hyperintensity (DPH) or hot cross bun (HCB) sign. In differentiating MSA-P from PD using FA and ADC values, we obtained equal sensitivity (70%) and higher specificity (100%) in the pons than in the putamen and cerebellum. In addition, all patients that had both significant low FA and high ADC values in each of these three areas were MSA-P cases, and those that had both normal FA and ADC values in the pons were all PD cases. Our diagnostic algorithm based on these results accurately diagnosed 90% of patients with MSA-P. CONCLUSION: FA and ADC values detected early pathological involvement prior to magnetic resonance signal changes in MSA. In particular, low FA values in the pons showed high specificity in discriminating MSA-P from PD. In addition, combined analysis of both FA and ADC values in all three areas was more useful than only one. PMID- 17353259 TI - Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer's disease. AB - OBJECTIVE: To evaluate the efficacy and safety of rapidly titrated rivastigmine administered twice (BID) or three times (TID) daily in patients with mild to moderate Alzheimer's disease (AD). METHODS: This was a 26 week international, randomised, double blind, placebo controlled study in which 678 patients with probable AD received placebo or rivastigmine 2-12 mg/day BID or TID. Primary outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS cog) and categorical analysis of the Clinician Interview Based Impression of Change incorporating caregiver information (CIBIC-Plus). Secondary outcomes were the CIBIC-Plus change from baseline, Progressive Deterioration Scale, ADAS-cogA, Mini-Mental State Examination and Global Deterioration Scale. RESULTS: At week 26, mean rivastigmine dose was 9.6 (2.76) mg/day in the TID group and 8.9 (2.93) mg/day in the BID group. Mean ADAS-cog changes from baseline in the TID and BID rivastigmine treated groups were -0.2 (SD 7.3) and 1.2 (SD 7.2) versus 2.8 (SD 7.2) for the placebo group (p<0.05). Differences between rivastigmine TID and placebo on the CIBIC-Plus categorical responder analysis were significant (31% vs 19%; p<0.05, intention to treat). No significant differences were seen between BID and placebo for this outcome measure. Adverse events were predominantly gastrointestinal, occurring mainly during dose titration. Withdrawal because of adverse events accounted for 17% of BID, 11% of TID and 9% of placebo patients. CONCLUSIONS: Rivastigmine administered as a BID or TID regimen significantly benefited cognitive, function and global performances in AD patients. The TID regimen showed a tendency for superior tolerability and permitted titration to higher doses, an outcome that is significant as the efficacy of rivastigmine is dose related. PMID- 17353260 TI - Secretion of the adipocyte-specific secretory protein adiponectin critically depends on thiol-mediated protein retention. AB - Adiponectin is a secretory protein abundantly secreted from adipocytes. It assembles into a number of different higher-order complexes. Adipocytes maintain tight control over circulating plasma levels, suggesting the existence of a complex, highly regulated biosynthetic pathway. However, the critical mediators of adiponectin maturation within the secretory pathway have not been elucidated. Previously, we found that a significant portion of de novo-synthesized adiponectin is not secreted and retained in adipocytes. Here, we show that there is an abundant pool of properly folded adiponectin in the secretory pathway that is retained through thiol-mediated retention, as judged by the release of adiponectin in response to treatment of adipocytes with reducing agents. Adiponectin is covalently bound to the ER chaperone ERp44. An adiponectin mutant lacking cysteine 39 fails to stably interact with ERp44, demonstrating that this residue is the primary site mediating the covalent interaction. Another ER chaperone, Ero1-Lalpha, plays a critical role in the release of adiponectin from ERp44. Levels of both of these proteins are highly regulated in adipocytes and are influenced by the metabolic state of the cell. While less critical for the secretion of trimers, these chaperones play a major role in the assembly of higher-order adiponectin complexes. Our data highlight the importance of posttranslational events controlling adiponectin levels and the release of adiponectin from adipocytes. One mechanism for increasing circulating levels of specific adiponectin complexes by peroxisome proliferator-activated receptor gamma agonists may be selective upregulation of rate-limiting chaperones. PMID- 17353262 TI - APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks. AB - Aprataxin and polynucleotide kinase (PNK) are DNA end processing factors that are recruited into the DNA single- and double-strand break repair machinery through phosphorylation-specific interactions with XRCC1 and XRCC4, respectively. These interactions are mediated through a divergent class of forkhead-associated (FHA) domain that binds to peptide sequences in XRCC1 and XRCC4 that are phosphorylated by casein kinase 2 (CK2). Here, we identify the product of the uncharacterized open reading frame C2orf13 as a novel member of this FHA domain family of proteins and we denote this protein APLF (aprataxin- and PNK-like factor). We show that APLF interacts with XRCC1 in vivo and in vitro in a manner that is stimulated by CK2. Yeast two-hybrid analyses suggest that APLF also interacts with the double-strand break repair proteins XRCC4 and XRCC5 (Ku86). We also show that endogenous and yellow fluorescent protein-tagged APLF accumulates at sites of H(2)O(2) or UVA laser-induced chromosomal DNA damage and that this is achieved through at least two mechanisms: one that requires the FHA domain-mediated interaction with XRCC1 and a second that is independent of XRCC1 but requires a novel type of zinc finger motif located at the C terminus of APLF. Finally, we demonstrate that APLF is phosphorylated in a DNA damage- and ATM-dependent manner and that the depletion of APLF from noncycling human SH-SY5Y neuroblastoma cells reduces rates of chromosomal DNA strand break repair following ionizing radiation. These data identify APLF as a novel component of the cellular response to DNA strand breaks in human cells. PMID- 17353261 TI - DeltaNp73 modulates nerve growth factor-mediated neuronal differentiation through repression of TrkA. AB - p73, a member of the p53 family, expresses two classes of proteins: the full length TAp73 and the N-terminally truncated DeltaNp73. While TAp73 possesses many p53-like features, DeltaNp73 is dominant negative towards TAp73 and p53 and appears to have distinct functions in tumorigenesis and neuronal development. Given its biological importance, we investigated the role of DeltaNp73 in nerve growth factor (NGF)-mediated neuronal differentiation in PC12 cells. We show that overexpression of DeltaNp73alpha or DeltaNp73beta inhibits NGF-mediated neuronal differentiation in both p53-dependent and -independent manners. In line with this, we showed that the level of endogenous DeltaNp73 is progressively diminished in differentiating PC12 cells upon NGF treatment and knockdown of DeltaNp73 promotes NGF-mediated neuronal differentiation. Interestingly, we found that the ability of DeltaNp73 to suppress NGF-mediated neuronal differentiation is correlated with its ability to regulate the expression of TrkA, the high affinity NGF receptor. Specifically, we found that DeltaNp73 directly binds to the TrkA promoter and transcriptionally represses TrkA expression, which in turn attenuates the NGF-mediated mitogen-activated protein kinase pathway. Conversely, the steady-state level of TrkA is increased upon knockdown of DeltaNp73. Furthermore, we found that histone deacetylase 1 (HDAC1) and HDAC2 are recruited by DeltaNp73 to the TrkA promoter and act as corepressors to suppress TrkA expression, which can be relieved by trichostatin A, an HDAC inhibitor. Taken together, we conclude that DeltaNp73 negatively regulates NGF-mediated neuronal differentiation by transrepressing TrkA. PMID- 17353263 TI - MEK1 and protein phosphatase 4 coordinate Dictyostelium development and chemotaxis. AB - The MEK and extracellular signal-regulated kinase/mitogen-activated protein kinase proteins are established regulators of multicellular development and cell movement. By combining traditional genetic and biochemical assays with a statistical analysis of global gene expression profiles, we discerned a genetic interaction between Dictyostelium discoideum mek1, smkA (named for its role in the suppression of the mek1(-) mutation), and pppC (the protein phosphatase 4 catalytic subunit gene). We found that during development and chemotaxis, both mek1 and smkA regulate pppC function. In other organisms, the protein phosphatase 4 catalytic subunit, PP4C, functions in a complex with the regulatory subunits PP4R2 and PP4R3 to control recovery from DNA damage. Here, we show that catalytically active PP4C is also required for development, chemotaxis, and the expression of numerous genes. The product of smkA (SMEK) functions as the Dictyostelium PP4R3 homolog and positively regulates a subset of PP4C's functions: PP4C-mediated developmental progression, chemotaxis, and the expression of genes specifically involved in cell stress responses and cell movement. We also demonstrate that SMEK does not control the absolute level of PP4C activity and suggest that SMEK regulates PP4C by controlling its localization to the nucleus. These data define a novel genetic pathway in which mek1 functions upstream of pppC-smkA to control multicellular development and chemotaxis. PMID- 17353264 TI - Efficient RNA polyuridylation by noncanonical poly(A) polymerases. AB - Nuclear poly(A) polymerase (PAP) polyadenylates nascent mRNAs, promoting their nuclear export, stability, and translation, while the related cytoplasmic polymerase GLD-2 activates translation of deadenylated mRNAs. Here we characterize the biochemical activity of fission yeast Schizosaccharomyces pombe Cid1, a putative cytoplasmic PAP implicated in cell cycle checkpoint controls. Surprisingly, Cid1 has robust poly(U) polymerase activity in vitro, especially when isolated in native multiprotein complexes. Furthermore, we found that upon S phase arrest, the 3' ends of actin mRNAs were posttranscriptionally uridylated in a Cid1-dependent manner. Finally, Hs2 (ZCCHC6), a human ortholog of Cid1, shows similar activity. These data suggest that uridylation of mRNA forms the basis of an evolutionarily conserved mechanism of gene regulation. PMID- 17353265 TI - Contribution of the serine 129 of histone H2A to chromatin structure. AB - Phosphorylation of a yeast histone H2A at C-terminal serine 129 has a central role in double-strand break repair. Mimicking H2A phosphorylation by replacement of serine 129 with glutamic acid (hta1-S129E) suggested that phosphorylation destabilizes chromatin structures and thereby facilitates the access of repair proteins. Here we have tested chromatin structures in hta1-S129 mutants and in a C-terminal tail deletion strain. We show that hta1-S129E affects neither nucleosome positioning in minichromosomes and genomic loci nor supercoiling of minichromosomes. Moreover, hta1-S129E has no effect on chromatin stability measured by conventional nuclease digestion, nor does it affect DNA accessibility and repair of UV-induced DNA lesions by nucleotide excision repair and photolyase in vivo. Similarly, deletion of the C-terminal tail has no effect on nucleosome positioning and stability. These data argue against a general role for the C terminal tail in chromatin organization and suggest that phosphorylated H2A, gamma-H2AX in higher eukaryotes, acts by recruitment of repair components rather than by destabilizing chromatin structures. PMID- 17353266 TI - Regulation of Notch1 gene expression by p53 in epithelial cells. AB - The E6 protein of cervical cancer-associated human papillomaviruses (HPVs) is known to suppress keratinocyte differentiation through unidentified mechanisms. Notch1 is a determinant of keratinocyte differentiation and functions as a tumor suppressor in mammalian epidermis. Here, we report that the Notch1 gene is a novel target of p53 and can be down-regulated by E6 through p53 degradation in normal human epithelial cells. Thus, inactivation of p53 by E6 or short-hairpin RNA (shRNA) resulted in reduced Notch1 expression at the transcription level, and a p53-responsive element could be identified in the Notch1 promoter. The expression of E6, p53 shRNA, or Notch1 shRNA suppressed both spontaneous keratinocyte differentiation in culture and its induction upon DNA damage. Furthermore, the induction of Notch1 and differentiation makers as well as thickening of the epidermal layer upon UV irradiation was observed in wild-type but not in p53-deficient mouse skin. Together, our findings not only demonstrate a novel link between p53 and Notch1 in keratinocyte differentiation upon genotoxic stress but also suggest a novel tumor suppressor mechanism of p53 in the development of squamous cell carcinomas, including HPV-induced tumors. PMID- 17353267 TI - MBD2 is required for correct spatial gene expression in the gut. AB - Gene expression in the gut is segmentally regulated, but little is known of the molecular origin of patterning. Analysis of gene expression in colons from mice lacking the methyl-CpG binding repressor MBD2 revealed frequent activation of genes that are normally only expressed in the exocrine pancreas and duodenum. Reduced DNA methylation activated the same gene set in the colon. No significant differences in DNA methylation between the colon and duodenum were detected, but MBD2 was significantly more abundant in the colon. The relevance of MBD2 concentration was tested in a human colon cancer cell line. Depletion of MBD2 was again found to activate exocrine pancreatic genes. Gene activation in this cell culture model was accompanied by loss of promoter-bound MBD2 and increased histone acetylation. The results suggest that modulation of MBD2 during gut development establishes a region-specific gene expression pattern that is essential for establishing correct segmental character. PMID- 17353268 TI - trans Autophosphorylation at DNA-dependent protein kinase's two major autophosphorylation site clusters facilitates end processing but not end joining. AB - Recent studies have established that DNA-dependent protein kinase (DNA-PK) undergoes a series of autophosphorylation events that facilitate successful completion of nonhomologous DNA end joining. Autophosphorylation at sites in two distinct clusters regulates DNA end access to DNA end-processing factors and to other DNA repair pathways. Autophosphorylation within the kinase's activation loop regulates kinase activity. Additional autophosphorylation events (as yet undefined) occur that mediate kinase dissociation. Here we provide the first evidence that autophosphorylation within the two major clusters (regulating end access) occurs in trans. Further, both UV-induced and double-strand break (DSB) induced phosphorylation in the two major clusters is predominantly autophosphorylation. Finally, we show that while autophosphorylation in trans on one of two synapsed DNA-PK complexes facilitates appropriate end processing, this is not sufficient to promote efficient end joining. This suggests that end joining in living cells requires additional phosphorylation events that either occur in cis or that occur on both sides of the DNA-PK synapse. These data support an emerging consensus that, via a series of autophosphorylation events, DNA-PK undergoes a sequence of conformational changes that promote efficient and appropriate repair of DSBs. PMID- 17353269 TI - Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit. AB - The PeBoW complex is essential for cell proliferation and maturation of the large ribosomal subunit in mammalian cells. Here we examined the role of PeBoW-specific proteins Pes1, Bop1, and WDR12 in complex assembly and stability, nucleolar transport, and pre-ribosome association. Recombinant expression of the three subunits is sufficient for complex formation. The stability of all three subunits strongly increases upon incorporation into the complex. Only overexpression of Bop1 inhibits cell proliferation and rRNA processing, and its negative effects could be rescued by coexpression of WDR12, but not Pes1. Elevated levels of Bop1 induce Bop1/WDR12 and Bop1/Pes1 subcomplexes. Knockdown of Bop1 abolishes the copurification of Pes1 with WDR12, demonstrating Bop1 as the integral component of the complex. Overexpressed Bop1 substitutes for endogenous Bop1 in PeBoW complex assembly, leading to the instability of endogenous Bop1. Finally, indirect immunofluorescence, cell fractionation, and sucrose gradient centrifugation experiments indicate that transport of Bop1 from the cytoplasm to the nucleolus is Pes1 dependent, while Pes1 can migrate to the nucleolus and bind to preribosomal particles independently of Bop1. We conclude that the assembly and integrity of the PeBoW complex are highly sensitive to changes in Bop1 protein levels. PMID- 17353270 TI - Nuclear factor I X deficiency causes brain malformation and severe skeletal defects. AB - The transcription factor family of nuclear factor I (NFI) proteins is encoded by four closely related genes: Nfia, Nfib, Nfic, and Nfix. A potential role for NFI proteins in regulating developmental processes has been implicated by their specific expression pattern during embryonic development and by analysis of NFI deficient mice. It was shown that loss of NFIA results in hydrocephalus and agenesis of the corpus callosum and that NFIB deficiency leads to neurological defects and to severe lung hypoplasia, whereas Nfic knockout mice exhibit specific tooth defects. Here we report the knockout analysis of the fourth and last member of this gene family, Nfix. Loss of NFIX is postnatally lethal and leads to hydrocephalus and to a partial agenesis of the corpus callosum. Furthermore, NFIX-deficient mice develop a deformation of the spine, which is due to a delay in ossification of vertebral bodies and a progressive degeneration of intervertebral disks. Impaired endochondral ossification and decreased mineralization were also observed in femoral sections of Nfix-/- mice. Consistent with the defects in bone ossification we could show that the expression level of tetranectin, a plasminogen-binding protein involved in mineralization, is specifically downregulated in bones of NFIX-deficient mice. PMID- 17353271 TI - Mbd2 contributes to DNA methylation-directed repression of the Xist gene. AB - Transcription of the Xist gene triggers X chromosome inactivation in cis and is therefore silenced on the X chromosome that remains active. DNA methylation contributes to this silencing, but the mechanism is unknown. As methylated DNA binding proteins (MBPs) are potential mediators of gene silencing by DNA methylation, we asked whether MBP-deficient cell lines could maintain Xist repression. The absence of Mbd2 caused significant low-level reactivation of Xist, but silencing was restored by exogenous Mbd2. In contrast, deficiencies of Mbd1, MeCP2, and Kaiso had no detectable effect, indicating that MBPs are not functionally redundant at this locus. Xist repression in Mbd2-null cells was hypersensitive to the histone deacetylase inhibitor trichostatin A and to depletion of the DNA methyltransferase Dnmt1. These synergies implicate Mbd2 as a mediator of the DNA methylation signal at this locus. The presence of redundant mechanisms to enforce repression at Xist and other loci is compatible with the hypothesis that "stacking" of imperfect repressive tendencies may be an evolutionary strategy to ensure leakproof gene silencing. PMID- 17353272 TI - Mus81-Eme1-dependent and -independent crossovers form in mitotic cells during double-strand break repair in Schizosaccharomyces pombe. AB - During meiosis, double-strand breaks (DSBs) lead to crossovers, thought to arise from the resolution of double Holliday junctions (HJs) by an HJ resolvase. In Schizosaccharomyces pombe, meiotic crossovers are produced primarily through a mechanism requiring the Mus81-Eme1 endonuclease complex. Less is known about the processes that produces crossovers during the repair of DSBs in mitotic cells. We employed an inducible DSB system to determine the role of Rqh1-Top3 and Mus81 Eme1 in mitotic DSB repair and crossover formation in S. pombe. In agreement with the meiotic data, crossovers are suppressed in cells lacking Mus81-Eme1. And relative to the wild type, rqh1Delta cells show a fourfold increase in crossover frequency. This suppression of crossover formation by Rqh1 is dependent on its helicase activity. We found that the synthetic lethality of cells lacking both Rqh1 and Eme1 is suppressed by loss of swi5(+), which allowed us to show that the excess crossovers formed in an rqh1Delta background are independent of Mus81 Eme1. This result suggests that a second process for crossover formation exists in S. pombe and is consistent with our finding that deletion of swi5(+) restored meiotic crossovers in eme1Delta cells. Evidence suggesting that Rqh1 also acts downstream of Swi5 in crossover formation was uncovered in these studies. Our results suggest that during Rhp51-dependent repair of DSBs, Rqh1-Top3 suppresses crossovers in the Rhp57-dependent pathway while Mus81-Eme1 and possibly Rqh1 promote crossovers in the Swi5-dependent pathway. PMID- 17353273 TI - PIASy-mediated sumoylation of Yin Yang 1 depends on their interaction but not the RING finger. AB - As a multifunctional protein, Yin Yang 1 (YY1) has been demonstrated to regulate both gene expression and protein posttranslational modifications. However, gaps still exist in our knowledge of how YY1 can be modified and what the consequences of its modifications are. Here we report that YY1 protein can be sumoylated both in vivo and in vitro. We have identified lysine 288 as the major sumoylation site of YY1. We also discovered that PIASy, a SUMO E3 ligase, is a novel YY1 interacting protein and can stimulate the sumoylation of YY1 both in vitro and in vivo. Importantly, the effects of PIASy mutants on in vivo YY1 sumoylation correlate with the YY1-PIASy interaction but do not depend on the RING finger domain of PIASy. This regulation is unique to YY1 sumoylation because PIASy mediated p53 sumoylation still relies on the integrity of PIASy, which is also true of all of the previously identified substrates of PIASy. In addition, PIASy colocalizes with YY1 in the nucleus, stabilizes YY1 in vivo, and differentially regulates YY1 transcriptional activity on different target promoters. This study demonstrates that YY1 is a target of SUMOs and reveals a novel feature of a SUMO E3 ligase in the PIAS family that selectively stimulates protein sumoylation independent of the RING finger domain. PMID- 17353274 TI - A novel Stat3 binding motif in Gab2 mediates transformation of primary hematopoietic cells by the Stk/Ron receptor tyrosine kinase in response to Friend virus infection. AB - Friend erythroleukemia virus has long served as a paradigm for the study of the multistage progression of leukemia. Friend virus infects erythroid progenitor cells, followed by an initial polyclonal expansion of infected cells, which is driven by the activation of a naturally occurring truncated form of the Stk receptor tyrosine kinase (Sf-Stk). Subsequently, the accumulation of additional mutations in p53 and the activation of PU.1 result in full leukemic transformation. The early stages of transformation induced by Friend virus are characterized in vitro by the Epo-independent growth of infected erythroblasts. We have shown previously that this transforming event requires the kinase activity and Grb2 binding site of Sf-Stk and the recruitment of a Grb2/Gab2 complex to Sf-Stk. Here, we demonstrate that Stat3 is required for the Epo independent growth of Friend virus-infected cells and that the activation of Stat3 by Sf-Stk is mediated by a novel Stat3 binding site in Gab2. These results underscore a central role for Stat3 in hematopoietic transformation and describe a previously unidentified role for Gab2 in the recruitment and activation of Stat3 in response to transforming signals generated by tyrosine kinases. PMID- 17353275 TI - Differential regulation of Foxo3a target genes in erythropoiesis. AB - The cooperation of stem cell factor (SCF) and erythropoietin (Epo) is required to induce renewal divisions in erythroid progenitors, whereas differentiation to mature erythrocytes requires the presence of Epo only. Epo and SCF activate common signaling pathways such as the activation of protein kinase B (PKB) and the subsequent phosphorylation and inactivation of Foxo3a. In contrast, only Epo activates Stat5. Both Foxo3a and Stat5 promote erythroid differentiation. To understand the interplay of SCF and Epo in maintaining the balance between renewal and differentiation during erythroid development, we investigated differential Foxo3a target regulation by Epo and SCF. Expression profiling revealed that a subset of Foxo3a targets was not inhibited but was activated by Epo. One of these genes was Cited2. Transcriptional control of Epo/Foxo3a-induced Cited2 was studied and compared with that of the Epo-repressed Foxo3a target Btg1. We show that in response to Epo, the allegedly growth-inhibitory factor Foxo3a associates with the allegedly growth-stimulatory factor Stat5 in the nucleus, which is required for Epo-induced Cited2 expression. In contrast, Btg1 expression is controlled by the cooperation of Foxo3a with cyclic AMP- and Jun kinase-dependent Creb family members. Thus, Foxo3a not only is an effector of PKB but also integrates distinct signals to regulate gene expression in erythropoiesis. PMID- 17353276 TI - The peptidyl prolyl cis/trans isomerase FKBP38 determines hypoxia-inducible transcription factor prolyl-4-hydroxylase PHD2 protein stability. AB - The heterodimeric hypoxia-inducible transcription factors (HIFs) are central regulators of the response to low oxygenation. HIF-alpha subunits are constitutively expressed but rapidly degraded under normoxic conditions. Oxygen dependent hydroxylation of two conserved prolyl residues by prolyl-4-hydroxylase domain-containing enzymes (PHDs) targets HIF-alpha for proteasomal destruction. We identified the peptidyl prolyl cis/trans isomerase FK506-binding protein 38 (FKBP38) as a novel interactor of PHD2. Yeast two-hybrid, glutathione S transferase pull-down, coimmunoprecipitation, colocalization, and mammalian two hybrid studies confirmed specific FKBP38 interaction with PHD2, but not with PHD1 or PHD3. PHD2 and FKBP38 associated with their N-terminal regions, which contain no known interaction motifs. Neither FKBP38 mRNA nor protein levels were regulated under hypoxic conditions or after PHD inhibition, suggesting that FKBP38 is not a HIF/PHD target. Stable RNA interference-mediated depletion of FKBP38 resulted in increased PHD hydroxylation activity and decreased HIF protein levels and transcriptional activity. Reconstitution of FKBP38 expression abolished these effects, which were independent of the peptidyl prolyl cis/trans isomerase activity. Downregulation of FKBP38 did not affect PHD2 mRNA levels but prolonged PHD2 protein stability, suggesting that FKBP38 is involved in PHD2 protein regulation. PMID- 17353277 TI - Cloning and functional analysis of hypothalamic homeobox gene Bsx1a and its isoform, Bsx1b. AB - The hypothalamus is a key regulatory unit of the neuroendocrine system and plays an essential role in energy balance and reproduction. Despite its important role, the molecular mechanisms underlying hypothalamic development are not fully understood. Here, we report molecular analyses of a newly identified murine homeobox gene, Bsx/Bsx1a, that is expressed in the developing and postnatal hypothalamus. We demonstrate that BSX1A is a DNA binding protein and a transcriptional activator. Transcriptional reporter assays identified the C terminal region of BSX1A as an activation domain. We have isolated an alternative splice form of Bsx1a, designated Bsx1b, which retains the N-terminal region but lacks the homeodomain. Analyses of subcellular localization using transfected cell lines revealed that BSX1A and BSX1B localize in the nuclei and cytoplasm, respectively. Immunohistochemical analyses suggested that both BSX1A and BSX1B are expressed in the neonatal hypothalamus. Taking these data together, we propose that alternative RNA splicing is involved in hypothalamic development/function. PMID- 17353278 TI - Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts. AB - Cadherins are the most crucial membrane proteins for the formation of tight and compact cell-cell contacts. Cadherin-based cell-cell adhesions are dynamically established and/or disrupted during various physiological and pathological processes. However, the molecular mechanisms that regulate cell-cell contacts are not fully understood. In this paper, we report a novel functional role of casein kinase 1 (CK1) in the regulation of cell-cell contacts. Firstly, we observed that IC261, a specific inhibitor of CK1, stabilizes cadherin-based cell-cell contacts, whereas the overexpression of CK1 disrupts them. CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846, a highly conserved residue between classical cadherins. Constitutively phosphorylated E-cadherin (S846D) is unable to localize at cell cell contacts and has decreased adhesive activity. Furthermore, phosphorylated E cadherin (S846D) has weaker interactions with beta-catenin and is internalized more efficiently than wild-type E-cadherin. These data indicate that CK1 is a novel negative regulator of cadherin-based cell-cell contacts. PMID- 17353279 TI - Induction of cell signaling events by the cholera toxin B subunit in antigen presenting cells. AB - Cholera toxin (CT) is one of the most effective and widely studied mucosal adjuvants. Although the ADP-ribosylating A subunit has been implicated in augmenting immune responses, the receptor-binding B subunit (CT-B) has greater immunogenicity and may be a repository of adjuvant activity without potential toxicity. In order to elucidate mechanisms of immune modulation by CT-B alone, primary B cells and macrophages were assessed for responses to CT-B in vitro, as measured by the expression of cell surface markers, cellular signaling events, and cytokine secretion. Increased phosphorylation of multiple signaling molecules, including Erk1/2 and p38, was detected. CT-B also induced transactivation of the transcription elements cyclic AMP-responsive element and NF-kappaB, the latter of which was inhibited by phosphotyrosine inhibition. While specific inhibition of MEK1/2 did not reduce CT-B induction of cell surface marker expression, it did attenuate CT-B-mediated interleukin-6 secretion. These data show that CT-B induces a set of signaling events related to cellular activation, surface molecule expression, and cytokine production that has potential implications for elucidating CT-B adjuvant activity in the absence of enzymatically active holotoxin. PMID- 17353280 TI - Haemophilus influenzae type a infection and its prevention. PMID- 17353282 TI - Identification of in vivo-expressed immunogenic proteins by serological proteome analysis of the Bacillus anthracis secretome. AB - In a previous comparative proteomic study of Bacillus anthracis examining the influence of the virulence plasmids and of various growth conditions on the composition of the bacterial secretome, we identified 64 abundantly expressed proteins (T. Chitlaru, O. Gat, Y. Gozlan, N. Ariel, and A. Shafferman, J. Bacteriol. 188:3551-3571, 2006). Using a battery of sera from B. anthracis infected animals, in the present study we demonstrated that 49 of these proteins are immunogenic. Thirty-eight B. anthracis immunogens are documented in this study for the first time. The relative immunogenicities of the 49 secreted proteins appear to span a >10,000-fold range. The proteins eliciting the highest humoral response in the course of infection include, in addition to the well established immunogens protective antigen (PA), Sap, and EA1, GroEL (BA0267), AhpC (BA0345), MntA (BA3189), HtrA (BA3660), 2,3-cyclic nucleotide diesterase (BA4346), collagen adhesin (BAS5205), an alanine amidase (BA0898), and an endopeptidase (BA1952), as well as three proteins having unknown functions (BA0796, BA0799, and BA0307). Of these 14 highly potent secreted immunogens, 11 are known to be associated with virulence and pathogenicity in B. anthracis or in other bacterial pathogens. Combining the results reported here with the results of a similar study of the membranal proteome of B. anthracis (T. Chitlaru, N. Ariel, A. Zvi, M. Lion, B. Velan, A. Shafferman, and E. Elhanany, Proteomics 4:677-691, 2004) and the results obtained in a functional genomic search for immunogens (O. Gat, H. Grosfeld, N. Ariel, I. Inbar, G. Zaide, Y. Broder, A. Zvi, T. Chitlaru, Z. Altboum, D. Stein, S. Cohen, and A. Shafferman, Infect. Immun. 74:3987-4001, 2006), we generated a list of 84 in vivo-expressed immunogens for future evaluation for vaccine development, diagnostics, and/or therapeutic intervention. In a preliminary study, the efficacies of eight immunogens following DNA immunization of guinea pigs were compared to the efficacy of a PA DNA vaccine. All eight immunogens induced specific high antibody titers comparable to the titers elicited by PA; however, unlike PA, none of them provided protection against a lethal challenge (50 50% lethal doses) of virulent B. anthracis strain Vollum spores. PMID- 17353283 TI - Wild-type and interleukin-10-deficient regulatory T cells reduce effector T-cell mediated gastroduodenitis in Rag2-/- mice, but only wild-type regulatory T cells suppress Helicobacter pylori gastritis. AB - CD4(+) CD45RB(hi) CD25(-) effector T cells (T(E)) promote Helicobacter pylori gastritis in mice, and CD4(+) CD45RB(lo) CD25(+) regulatory T cells (T(R)) are anti-inflammatory. Using adoptive transfer into H. pylori-infected Rag2(-/-) mice, we evaluated effects of wild-type (wt) C57BL/6 or congenic interleukin-10 deficient (IL-10(-/-)) T(R) cells on gastritis, gastric cytokines, and H. pylori colonization. Infected Rag2(-/-) mice colonized in the corpus and antrum with 10(5) to 10(6) H. pylori CFU/gram without associated gastritis. T(E) cell transfer caused morbidity and an H. pylori-independent pangastritis and duodenitis (gastroduodenitis) associated with increased expression of gamma interferon (IFN-gamma) and tumor necrosis factor alpha. T(E) cell transfer to H. pylori-infected mice led to additive corpus gastritis associated with inflammatory cytokine expression and reduced colonization. wt T(R) cells reduced morbidity, H. pylori corpus gastritis, gastroduodenitis, and inflammatory cytokine expression and reversed the decline in H. pylori colonization attributable to T(E) cells. Although less effective than wt T(R) cells, IL-10(-/ ) T(R) cells also reduced morbidity and gastroduodenitis but did not reduce H. pylori corpus gastritis or impact T(E) cell inhibition of colonization. Gastric tissues from mice receiving wt T(R) cells expressed higher levels of Foxp3 compared to recipients of IL-10(-/-) T(R) cells, consistent with lower regulatory activity of IL-10(-/-) T(R) cells. These results demonstrate that wt T(R) cells suppressed T(E)-cell-mediated H. pylori-independent gastroduodenitis and H. pylori-dependent corpus gastritis more effectively than IL-10(-/-) T(R) cells. Compartmental differences in T(E)-cell- and H. pylori-mediated inflammation and in regulatory effects between wt T(R) and IL-10(-/-) T(R) cells suggest that IL 10 expression by wt T(R) cells is important to regulatory suppression of gastric inflammation. PMID- 17353281 TI - Microevolution and patterns of dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans. AB - The natural history, microevolution, and patterns of interindividual transmission and global dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans were studied by population genetic analysis. The JP2 clone is strongly associated with aggressive periodontitis in adolescents of African descent and differs from other clones of the species by several genetic peculiarities, including a 530-bp deletion in the promoter region of the leukotoxin gene operon, which results in increased leukotoxic activity. Multilocus sequence analysis of 82 A. actinomycetemcomitans strains, 66 of which were JP2 clone strains collected over a period of more than 20 years, confirmed that there is a clonal population structure with evolutionary lineages corresponding to serotypes. Although genetically highly conserved, as shown by alignment of sequences of eight housekeeping genes, strains belonging to the JP2 clone had a number of point mutations, particularly in the pseudogenes hbpA and tbpA. Characteristic mutations allowed isolates from individuals from the Mediterranean area and from West Africa, including the Cape Verde Islands, to be distinguished. The patterns of mutations indicate that the JP2 clone initially emerged as a distinct genotype in the Mediterranean part of Africa approximately 2,400 years ago and subsequently spread to West Africa, from which it was transferred to the American continents during the transatlantic slave trade. The sustained exclusive colonization of individuals of African descent despite geographical separation for centuries suggests that the JP2 clone has a distinct host tropism. The colonization of family members by JP2 clone strains with unique point mutations provides strong evidence that there is intrafamilial transmission and suggests that dissemination of the JP2 clone is restricted to close contacts. PMID- 17353284 TI - A genetic screen for Mycobacterium tuberculosis mutants defective for phagosome maturation arrest identifies components of the ESX-1 secretion system. AB - After phagocytosis, the intracellular pathogen Mycobacterium tuberculosis arrests the progression of the nascent phagosome into a phagolysosome, allowing for replication in a compartment that resembles early endosomes. To better understand the molecular mechanisms that govern phagosome maturation arrest, we performed a visual screen on a set of M. tuberculosis mutants specifically attenuated for growth in mice to identify strains that failed to arrest phagosome maturation and trafficked to late phagosomal compartments. We identified 10 such mutants that could be partitioned into two classes based on the kinetics of trafficking. Importantly, four of these mutants harbor mutations in genes that encode components of the ESX-1 secretion system, a pathway critical for M. tuberculosis virulence. Although ESX-1 is required, the known ESX-1 secreted proteins are dispensable for phagosome maturation arrest, suggesting that a novel effector required for phagosome maturation arrest is secreted by ESX-1. Other mutants identified in this screen had mutations in genes involved in lipid synthesis and secretion and in molybdopterin biosynthesis, as well as in genes with unknown functions. Most of these trafficking mutants exhibited a corresponding growth defect during macrophage infection, but two mutants grew like wild-type M. tuberculosis during macrophage infection. Our results support the emerging consensus that multiple factors from M. tuberculosis, including the ESX-1 secretion system, are involved in modulating trafficking within the host. PMID- 17353285 TI - Complement receptor 3 and Toll-like receptor 4 act sequentially in uptake and intracellular killing of unopsonized Salmonella enterica serovar Typhimurium by human neutrophils. AB - The uptake and subsequent killing of Salmonella enterica serovar Typhimurium by human neutrophils was studied. In particular, two pattern recognition receptors, complement receptor 3 (CR3) and Toll-like receptor 4 (TLR4), were found to be essential for the efficient uptake and activation, respectively, of the NADPH oxidase. The uptake of Salmonella was almost completely inhibited by various monoclonal antibodies against CR3, and neutrophils from a patient with leukocyte adhesion deficiency type 1, which lack CR3, showed almost no uptake of Salmonella. A lipopolysaccharide (LPS) mutant strain of Salmonella was used to show that the expression of full-length, wild-type, or so-called smooth LPS is important for the efficient killing of intracellular Salmonella. Infection with wild-type-LPS-expressing Salmonella resulted in the generation of reactive oxygen species (ROS) in TLR4-decorated, Salmonella-containing vacuoles, whereas ROS were not induced by an LPS mutant strain. In addition, the recognition of Salmonella by neutrophils, leading to ROS production, was shown to be intracellular, as determined by priming experiments with intact bacteria under conditions where the bacterium is not taken up. Finally, the generation of ROS in the wild-type Salmonella-infected neutrophils was largely inhibited by the action of a TLR4 blocking, cell-permeable peptide, showing that signaling by this receptor from the Salmonella-containing vacuole is essential for the activation of the NADPH oxidase. In sum, our data identify the sequential recognition of unopsonized Salmonella strains by CR3 and TLR4 as essential events in the efficient uptake and killing of this intracellular pathogen. PMID- 17353286 TI - Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine schistosomiasis. AB - CD1d-restricted natural killer T (NKT) cells represent a heterogeneous population of innate memory immune cells expressing both NK and T-cell markers distributed into two major subsets, i.e., invariant NKT (iNKT) cells, which express exclusively an invariant T-cell receptor (TCR) alpha chain (Valpha14Jalpha18 in mice), and non-iNKT cells, which express more diverse TCRs. NKT cells quickly produce Th1- and/or Th2-type cytokines following stimulation with glycolipid antigen (Ag) and, through this property, play potent immunoregulatory roles in autoimmune diseases, cancer, and infection. No study has addressed the role of NKT cells in metazoan parasite infections so far. We show that during murine schistosomiasis, the apparent frequency of both iNKT cells and non-iNKT cells decreased in the spleen as early as 3 weeks postinfection (p.i.) and that both populations expressed a greater amount of the activation marker CD69 at 6 weeks p.i., suggesting an activated phenotype. Two different NKT-cell-deficient mouse models, namely, TCR Jalpha18-/- (exclusively deficient in iNKT cells) and CD1d-/- (deficient in both iNKT and non-iNKT cells) mice, were used to explore the implication of these subsets in infection. We show that whereas both iNKT and non iNKT cells do not have a major impact on the immune response during the early phase (1 and 4 weeks) of infection, they exert important, although opposite, effects on the immune response during the acute phase of the disease (7 and 12 weeks), after schistosome egg production. Indeed, iNKT cells contribute to Th1 cell differentiation whereas non-iNKT cells might be mostly implicated in Th2 cell differentiation in response to parasite Ag. Our findings suggest, for the first time, that helminths activate both iNKT and non-iNKT cells in vivo, enabling them to differentially influence the Th1/Th2 balance of the immune response. PMID- 17353287 TI - Host cell responses to Chlamydia pneumoniae in gamma interferon-induced persistence overlap those of productive infection and are linked to genes involved in apoptosis, cell cycle, and metabolism. AB - The respiratory pathogen Chlamydia (Chlamydophila) pneumoniae is associated with chronic diseases, including atherosclerosis and giant-cell arteritis, which are accompanied by the occurrence of these obligate intracellular bacteria in blood vessels. There, C. pneumoniae seems to be present in a persistent state. Persistence is characterized by modified bacterial metabolism and morphology, as well as a reversible arrest of chlamydial development. In cell culture, this persistent state can be induced by gamma interferon (IFN-gamma). To elucidate this long-term interaction between chlamydiae and their host cells, microarray screening on epithelial HeLa cells was performed. Transcription of persistently (and productively) infected cells was compared with that of mock-infected cells. Sixty-six host cell genes were regulated at 24 h and/or 96 h of IFN-gamma-induced persistence. Subsequently, a set of 17 human host cell genes related to apoptosis, cell cycle, or metabolism was identified as permanently up- or down regulated by real-time PCR. Some of these chlamydia-dependent host cell responses were diminished or even absent in the presence of rifampin. However, other expression patterns were not altered by the inhibition of bacterial RNA polymerase, suggesting two different modes of host cell activation. Thus, in the IFN-gamma model, the persisting bacteria cause long-lasting changes in the expression of genes coding for functionally important proteins. They might be potential drug targets for the treatment of persistent C. pneumoniae infections. PMID- 17353288 TI - Relaxed cleavage specificity of an immunoglobulin A1 protease from Neisseria meningitidis. AB - Respiratory pathogens, such as Neisseria meningitidis, secrete site-specific proteases able to cleave human immunoglobulin A1 (IgA1), the first line of defense at mucosal membranes. Bacterial isolates show wide variability in IgA1 protease activity, and those isolated from patients with clinical infection possess the highest levels of activity. A feature of this enzyme is the self cleavage required for secretion of the mature extracellular form. Known cleavage targets contain a proline-rich consensus recognition sequence, Pro-Pro-Ser-Pro, residing in the variable linker region that connects the protease and translocator domains. Here, we report the sequence of the NMB IgA1 protease and the unexpected self-cleavage and subsequent extracellular release of mature IgA1 protease from mutants lacking the previously defined consensus cleavage site. We investigated the possible link between enzyme secretion and variability in the linker sequence segment using site-directed mutagenesis and linker domain swapping to construct mutated and chimeric forms of the IgA1 protease from N. meningitidis strain NMB. The observed change in secreted activity levels compared to the wild-type clone indicated that the precise amino acid sequence of the intervening region, between mature IgA1 protease and the beta-core translocator domain, influences the efficacy of autoproteolytic processing. The broader specificity uncovered for the NMB IgA1 protease suggests that it could cleave a far wider range of human proteins than previously appreciated. PMID- 17353289 TI - The salmochelin siderophore receptor IroN contributes to invasion of urothelial cells by extraintestinal pathogenic Escherichia coli in vitro. AB - Extraintestinal pathogenic Escherichia coli (ExPEC) strains possess several siderophore-dependent iron uptake systems. In this study we demonstrated that the salmochelin siderophore receptor IroN is involved in the invasion of urothelial cells by ExPEC in vitro. Thus, IroN may play a dual role in the establishment of urinary tract infections, displaying an iron uptake receptor as well as an internalization factor. PMID- 17353290 TI - Murine aerosol challenge model of anthrax. AB - The availability of relevant and useful animal models is critical for progress in the development of effective vaccines and therapeutics. The infection of rabbits and non-human primates with fully virulent Bacillus anthracis spores provides two excellent models of anthrax disease. However, the high cost of procuring and housing these animals and the specialized facilities required to deliver fully virulent spores limit their practical use in early stages of product development. Conversely, the small size and low cost associated with using mice makes this animal model more practical for conducting experiments in which large numbers of animals are required. In addition, the availability of knockout strains and well characterized immunological reagents makes it possible to perform studies in mice that cannot be performed easily in other species. Although we, along with others, have used the mouse aerosol challenge model to examine the outcome of B. anthracis infection, a detailed characterization of the disease is lacking. The current study utilizes a murine aerosol challenge model to investigate disease progression, innate cytokine responses, and histological changes during the course of anthrax after challenge with aerosolized spores. Our results show that anthrax disease progression in a complement-deficient mouse after challenge with aerosolized Sterne spores is similar to that described for other species, including rabbits and non-human primates, challenged with fully virulent B. anthracis. Thus, the murine aerosol challenge model is both useful and relevant and provides a means to further investigate the host response and mechanisms of B. anthracis pathogenesis. PMID- 17353291 TI - Deficiencies of myeloid differentiation factor 88, Toll-like receptor 2 (TLR2), or TLR4 produce specific defects in macrophage cytokine secretion induced by Helicobacter pylori. AB - Helicobacter pylori is a gram-negative microaerophilic bacterium that colonizes the gastric mucosa, leading to disease conditions ranging from gastritis to cancer. Toll-like receptors (TLRs) play a central role in innate immunity by their recognition of conserved molecular patterns on bacteria, fungi, and viruses. Upon recognition of microbial components, these TLRs associate with several adaptor molecules, including myeloid differentiation factor 88 (MyD88). To investigate the contribution of the innate immune system to H. pylori infection, bone marrow-derived macrophages from mice deficient in TLR2, TLR4, TLR9, and MyD88 were infected with H. pylori SS1 and SD4 for 24 or 48 h. We demonstrate that MyD88 was essential for H. pylori induction of all cytokines investigated except alpha interferon (IFN-alpha). The secretion of IFN-alpha was substantially increased from cells deficient in MyD88. H. pylori induced interleukin-12 (IL-12) and IL-10 through TLR4/MyD88 signaling. In addition, H. pylori induced less IL-6 and IL-1beta in TLR2-deleted macrophages, suggesting that the MyD88 pathway activated by TLR2 stimulation is responsible for H. pylori induction of the host proinflammatory response (IL-6 and IL-1beta). These observations are important in light of a recent report on IL-6 and IL-1beta playing a role in the development of H. pylori-related gastric cancer. In conclusion, our study demonstrates that H. pylori activates TLR2 and TLR4, leading to the secretion of distinct cytokines by macrophages. PMID- 17353292 TI - NRAMP1 3' untranslated region polymorphisms are not associated with natural resistance to Brucella abortus in cattle. AB - The NRAMP1 gene encodes a divalent cation transporter, located in the phagolysosomal membrane of macrophages, that has been associated with resistance to intracellular pathogens. In cattle, natural resistance against brucellosis has been associated with polymorphisms at the 3' untranslated region (3'UTR) of the NRAMP1 gene, which are detectable by single-strand conformational analysis (SSCA). This study aimed to evaluate the association between NRAMP1 3'UTR polymorphisms and resistance against bovine brucellosis in experimental and natural infections. In experimentally infected pregnant cows, abortion occurred in 42.1% of cows with a resistant genotype (SSCA(r); n = 19) and in 43.1% of those with a susceptible genotype (SSCA(s); n = 23). Furthermore, no association between intensity of pathological changes and genotype was detected. In a farm with a very high prevalence of bovine brucellosis, the percentages of strains of the SSCA(r) genotype were 86 and 84% in serologically positive (n = 64) and negative (n = 36) cows, respectively. Therefore, no association was found between the NRAMP1-resistant allele and the resistant phenotype in either experimental or naturally occurring brucellosis. To further support these results, bacterial intracellular survival was assessed in bovine monocyte-derived macrophages from cattle with either the resistant or susceptible genotype. In agreement with our previous results, no difference was observed in the rates of intracellular survival of B. abortus within macrophages from cattle with susceptible or resistant genotypes. Taken together, these results indicate that these polymorphisms at the NRAMP1 3'UTR do not affect resistance against B. abortus in cattle and that they are therefore not suitable markers of natural resistance against bovine brucellosis. PMID- 17353293 TI - The ChrA-ChrS and HrrA-HrrS signal transduction systems are required for activation of the hmuO promoter and repression of the hemA promoter in Corynebacterium diphtheriae. AB - Transcription of the Corynebacterium diphtheriae hmuO gene, which encodes a heme oxygenase involved in heme iron utilization, is activated in a heme- or hemoglobin-dependent manner in part by the two-component system ChrA-ChrS. Mutation of either the chrA or the chrS gene resulted in a marked reduction of hemoglobin-dependent activation at the hmuO promoter in C. diphtheriae; however, it was observed that significant levels of hemoglobin-dependent expression were maintained in the mutants, suggesting that an additional activator is involved in regulation. A BLAST search of the C. diphtheriae genome sequence revealed a second two-component system, encoded by DIP2268 and DIP2267, that shares similarity with ChrS and ChrA, respectively; we have designated these genes hrrS (DIP2268) and hrrA (DIP2267). Analysis of hmuO promoter expression demonstrated that hemoglobin-dependent activity was fully abolished in strains from which both the chrA-chrS and the hrrA-hrrS two-component systems were deleted. Similarly, deletion of the sensor kinase genes chrS and hrrS or the genes encoding both of the response regulators chrA and hrrA also eliminated hemoglobin-dependent activation at the hmuO promoter. We also show that the regulators ChrA-ChrS and HrrA-HrrS are involved in the hemoglobin-dependent repression of the promoter upstream of hemA, which encodes a heme biosynthesis enzyme. Evidence for cross talk between the ChrA-ChrS and HrrA-HrrS systems is presented. In conclusion, these findings demonstrate that the ChrA-ChrS and HrrA-HrrS regulatory systems are critical for full hemoglobin-dependent activation at the hmuO promoter and also suggest that these two-component systems are involved in the complex mechanism of the regulation of heme homeostasis in C. diphtheriae. PMID- 17353294 TI - Perspectives and limitations of microarray-based gene expression profiling of thyroid tumors. AB - Microarray technology has become a powerful tool to analyze the gene expression of tens of thousands of genes simultaneously. Microarray-based gene expression profiles are available for malignant thyroid tumors (i.e., follicular thyroid carcinoma, and papillary thyroid carcinoma), and for benign thyroid tumors (such as autonomously functioning thyroid nodules and cold thyroid nodules). In general, the two main foci of microarray investigations are improved understanding of the pathophysiology/molecular etiology of thyroid neoplasia and the detection of genetic markers that could improve the differential diagnosis of thyroid tumors. Their results revealed new features, not known from one-gene studies. Simultaneously, the increasing number of microarray analyses of different thyroid pathologies raises the demand to efficiently compare the data. However, the use of different microarray platforms complicates cross-analysis. In addition, there are other important differences between these studies: 1) some studies use intraindividual comparisons, whereas other studies perform interindividual comparisons; 2) the reference tissue is defined as strictly nonnodular healthy tissue or also contains benign lesions such as goiter, follicular adenoma, and hyperplastic nodules in some studies; and 3) the widely used Affymetrix GeneChip platform comprises several GeneChip generations that are only partially compatible. Moreover, the different studies are characterized by strong differences in data analysis methods, which vary from simple empiric filters to sophisticated statistic algorithms. Therefore, this review summarizes and compares the different published reports in the context of their study design. It also illustrates perspectives and solutions for data set integration and meta-analysis, as well as the possibilities to combine array analysis with other genetic approaches. PMID- 17353295 TI - beta-cell failure in diabetes and preservation by clinical treatment. AB - There is a progressive deterioration in beta-cell function and mass in type 2 diabetics. It was found that islet function was about 50% of normal at the time of diagnosis, and a reduction in beta-cell mass of about 60% was shown at necropsy. The reduction of beta-cell mass is attributable to accelerated apoptosis. The major factors for progressive loss of beta-cell function and mass are glucotoxicity, lipotoxicity, proinflammatory cytokines, leptin, and islet cell amyloid. Impaired beta-cell function and possibly beta-cell mass appear to be reversible, particularly at early stages of the disease where the limiting threshold for reversibility of decreased beta-cell mass has probably not been passed. Among the interventions to preserve or "rejuvenate" beta-cells, short term intensive insulin therapy of newly diagnosed type 2 diabetes will improve beta-cell function, usually leading to a temporary remission time. Another intervention is the induction of beta-cell "rest" by selective activation of ATP sensitive K+ (K(ATP)) channels, using drugs such as diazoxide. A third type of intervention is the use of antiapoptotic drugs, such as the thiazolidinediones (TZDs), and incretin mimetics and enhancers, which have demonstrated significant clinical evidence of effects on human beta-cell function. The TZDs improve insulin secretory capacity, decrease beta-cell apoptosis, and reduce islet cell amyloid with maintenance of neogenesis. The TZDs have indirect effects on beta cells by being insulin sensitizers. The direct effects are via peroxisome proliferator-activated receptor gamma activation in pancreatic islets, with TZDs consistently improving basal beta-cell function. These beneficial effects are sustained in some individuals with time. There are several trials on prevention of diabetes with TZDs. Incretin hormones, which are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose dependent insulin secretion from the pancreas, aid the overall maintenance of glucose homeostasis through slowing of gastric emptying, inhibition of glucagon secretion, and control of body weight. From the two major incretins, glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), only the first one or its mimetics or enhancers can be used for treatment because the diabetic beta-cell is resistant to GIP action. Because of the rapid inactivation of GLP-1 by dipeptidyl peptidase (DPP)-IV, several incretin analogs were developed: GLP-1 receptor agonists (incretin mimetics) exenatide (synthetic exendin-4) and liraglutide, by conjugation of GLP-1 to circulating albumin. The acute effect of GLP-1 and GLP-1 receptor agonists on beta-cells is stimulation of glucose-dependent insulin release, followed by enhancement of insulin biosynthesis and stimulation of insulin gene transcription. The chronic action is stimulating beta-cell proliferation, induction of islet neogenesis, and inhibition of beta-cell apoptosis, thus promoting expansion of beta-cell mass, as observed in rodent diabetes and in cultured beta-cells. Exenatide and liraglutide enhanced postprandial beta-cell function. The inhibition of the activity of the DPP-IV enzyme enhances endogenous GLP-1 action in vivo, mediated not only by GLP 1 but also by other mediators. In preclinical studies, oral active DPP-IV inhibitors (sitagliptin and vildagliptin) also promoted beta-cell proliferation, neogenesis, and inhibition of apoptosis in rodents. Meal tolerance tests showed improvement in postprandial beta-cell function. Obviously, it is difficult to estimate the protective effects of incretin mimetics and enhancers on beta-cells in humans, and there is no clinical evidence that these drugs really have protective effects on beta-cells. PMID- 17353296 TI - Attenuated anterior cingulate activation during a verbal fluency task in elderly patients with a history of multiple-episode depression. AB - OBJECTIVE: Previous studies have suggested that, in elderly patients, prior depression plays a role in the recurrence of depression. The aim of this study was to investigate cerebral brain function in recovered depressed elderly and investigate the relationship between this brain function and the number of depressive episodes. METHODS: Twenty elderly depressive patients in recovery and 10 healthy volunteers were included in this study. The depressive patients were divided into those who had experienced a single depressive episode and those who had experienced multiple episodes. Functional magnetic resonance imaging was performed in each participant during a verbal fluency task. The data were analyzed using statistical parametric mapping. RESULTS: Activation in the anterior cingulate cortex was significantly attenuated in patients who had experienced multiple depressive episodes, compared with the other two groups. There were no significant differences in areas of activation between patients with a single depressive episode and healthy volunteers. CONCLUSIONS: These findings suggest that attenuated activation in the anterior cingulate cortex may be associated with multiple episodes of depression in the elderly and with the vulnerability to cycling or recurrence. PMID- 17353297 TI - Depressive symptoms as a predictor of cognitive decline: MacArthur Studies of Successful Aging. AB - OBJECTIVE: The prevalence of dementia continues to rise, and yet, there are few known modifiable risk factors. Depression, as a treatable condition, may be important in the development of dementia. Our objective was to examine the association between depressive symptoms and longitudinal cognitive changes in older adults who were high-functioning at baseline. METHODS: The authors analyzed data from a community-based cohort (aged 70-79 at baseline), who, at study entry, scored 7 or more (out of 9) on the Short Portable Mental Status Questionnaire (SPMSQ). Depressive symptoms were assessed at baseline using the depression subscale of the Hopkins Symptom Check List. Cognitive performance was measured at baseline and at seven-year follow up by the SPMSQ and by summary scores from standard tests of naming, construction, spatial recognition, abstraction, and delayed recall. RESULTS: After adjusting for potential confounders, including age, education, and chronic health conditions such as diabetes, heart attack, stroke, and hypertension, a higher number of baseline depressive symptoms were strongly associated with greater seven-year decline in cognitive performance and with higher odds of incident cognitive impairment, i.e., decline in SPMSQ score to < or = 6 (adjusted odds ratio per quartile of depressive symptoms score: 1.34, 95% confidence interval: 1.10-1.68). CONCLUSIONS: Depressive symptomatology independently predicts cognitive decline and incident cognitive impairment in previously high-functioning older persons. PMID- 17353298 TI - Efficacy of a pill-swallowing training intervention to improve antiretroviral medication adherence in pediatric patients with HIV/AIDS. AB - OBJECTIVE: We aimed to retrospectively assess the efficacy of pill-swallowing training provided as a clinical intervention to referred pediatric patients with HIV in relation to improved adherence and subsequent related health outcomes. The primary goal of this study was to demonstrate participation in pill-swallowing training is associated with improved medication adherence as documented by routine pharmacy pill counts. Secondary objectives were to assess corresponding improvements in clinically observed biologic indicators of adherence, specifically, immunologic functioning (CD4+ T-cell%) and viral load, over time. PATIENTS AND METHODS: A retrospective chart review of 23 pediatric patients with HIV aged 4 to 21 years who were clinically referred for pill-swallowing training by an experienced pediatric psychologist for either noted difficulties with currently prescribed antiretroviral regimens and/or desire to change the child's regimen/formulary. Patient demographics, reason(s) for pill-swallowing training referral, number of pill-swallowing training sessions required to attain success, adherence, CD4+ T-cell%, and viral load were abstracted at baseline and at approximately 3 and 6 months posttraining. RESULTS: Modal number of sessions required to acquire the pill-swallowing skill was 1 session. Younger children (aged 4-5 years) required a median of 2 training sessions, while older children required > or = 3 sessions. A significant improvement in adherence from baseline to 6 months post-pill-swallowing training completion was observed, as were significant related improvements in CD4+ T-cell% and viral load. CONCLUSIONS: Participation in pill-swallowing training related to improved medication adherence at 6 months posttraining. Subsequent improvements in related CD4+ T cell% and viral load were noted over time, most significantly at 6 months postintervention. These preliminary findings provide justification for additional study via a prospective, randomized, controlled clinical trial. Pill-swallowing training potentially is a successful time-limited, cost-effective intervention to improve adherence to antiretroviral therapies, and thus medical status, in children with HIV. PMID- 17353299 TI - Declines in low birth weight and preterm birth among infants who were born to HIV infected women during an era of increased use of maternal antiretroviral drugs: Pediatric Spectrum of HIV Disease, 1989-2004. AB - OBJECTIVE: Our goal was to determine trends in low birth weight and preterm birth among US infants born to HIV-infected women. METHODS: We used data from the longitudinal Pediatric Spectrum of HIV Disease, a large HIV cohort, to assess trends in low birth weight and preterm birth from 1989 to 2004 among 11,321 study infants. Among women with prenatal care, we also assessed risk factors, including maternal antiretroviral therapy during pregnancy, that were predictive of low birth weight and preterm birth using univariate and multivariate logistic regression models. RESULTS: Overall, 11,231 of 14,464 infants who were enrolled in Pediatric Spectrum of HIV Disease were tested during the neonatal period. From 1989 to 2004, testing increased from 32% to 97%. The proportion of HIV-exposed infants who had low birth weight decreased from 35% to 21% and occurred in all racial/ethnic groups. Prevalence of preterm birth decreased from 35% to 22% and occurred in all groups. Any maternal antiretroviral therapy use increased from 2% to 84%. Among 8793 women who had prenatal care, low birth weight was associated with a history of illicit maternal drug use, unknown maternal HIV status before delivery, symptomatic maternal HIV disease, black race, Hispanic ethnicity, and infant HIV infection. Antiretroviral therapy or lack of it was not associated with low birth weight. Among women with prenatal care, preterm birth was associated with a history of illicit maternal drug use, symptomatic maternal HIV disease, no antiretroviral therapy, receipt of a 3-drug highly active antiretroviral therapy regimen with protease inhibitors, black race, and infant HIV infection. CONCLUSIONS: The proportion of infants who had low birth weight or were born preterm declined during an era of increased maternal antiretroviral therapies. These Pediatric Spectrum of HIV Disease trends differ from the overall increases in both outcomes among the US population. PMID- 17353300 TI - Mycoplasma pneumoniae and atypical Stevens-Johnson syndrome: a case series. AB - Mycoplasma pneumoniae is a common cause of community-acquired respiratory illness in the adolescent population. Stevens-Johnson syndrome is an extrapulmonary manifestation that has been associated with M. pneumoniae infections. Three adolescent males presented within a 1-month period with M. pneumoniae respiratory illnesses and severe mucositis but without the classic rash typical of Stevens Johnson. Diagnosis was facilitated by the use of a polymerase chain reaction based assay. This case series highlights the potential for M. pneumoniae associated Stevens-Johnson syndrome to occur without rash and supports the use of polymerase chain reaction for early diagnosis. PMID- 17353301 TI - Cerebral aneurysms in a patient with osteogenesis imperfecta and exon 28 polymorphism of COL1A2. PMID- 17353302 TI - T2 hypointense signal of rathke cleft cyst. PMID- 17353303 TI - Interventional neuroradiology: the role of experimental models in scientific progress. AB - SUMMARY: The ultimate methodology necessary to adopt a treatment as generally beneficial is the randomized controlled trial, a method designed by and for clinicians to maximize the care of their patients in the presence of uncertainty. Some selection is however necessary to limit trials to more promising and less risky endeavors. Experimental models are the privileged answer to the problem of finding scientific evidence while refraining from harming patients in the course of this pursuit. They allow a step by step assessment, from simple but artificial settings to more complex and realistic animal models. But the use of animal models can only be justified if the community can be convinced that alternatives have been considered but are invalid, when the project is scientifically sound and methodologically irreproachable. As neurointerventional methods develop and gain wider clinical applications, progress should proceed in an orderly fashion, within limits set by prudence and human values, from the less risky, costly, time consuming methods, to the more definite, pragmatic, labor intensive but inescapable clinical trials. Each step is essential and the sequence cannot be violated without risks of errors that eventually translate into clinical morbidity. PMID- 17353304 TI - Neuropathology for the neuroradiologist: fluorescence in situ hybridization. AB - SUMMARY: Fluorescence in situ hybridization is a molecular cytogenetic technique that localizes segments of DNA within tumor cells by using dyes that are visible with a fluorescent microscope. The technique has proved useful in typing a variety of tumors such as oligodendrogliomas and in understanding the genetic forces driving oncogenesis. PMID- 17353305 TI - Diffusion MR imaging in multiple sclerosis: technical aspects and challenges. AB - SUMMARY: Diffusion tensor (DT) MR imaging has frequently been applied in multiple sclerosis (MS) because of its ability to detect and quantify disease-related changes of the tissue microstructure within and outside T2-visible lesions. DT MR imaging data collection places high demands on scanner hardware and, though the acquisition and postprocessing can be relatively straightforward, numerous challenges remain in improving the reproducibility of this technique. Although there are some issues concerning image quality, echo-planar imaging is the most widely used acquisition scheme for diffusion imaging studies. Once the DT is estimated, indexes conveying the size, shape, and orientation of the DT can be calculated and further analyzed by using either histogram- or region-of-interest based analyses. Because the orientation of the DT reflects the orientation of the axonal fibers of the brain, the pathways of the major white matter tracts can also be visualized. The DT model of diffusion, however, is not sufficient to characterize the diffusion properties of the brain when complex populations of fibers are present in a single voxel, and new ways to address this issue have been proposed. Two developments have enabled considerable improvements in the application of DT MR imaging: high magnetic field strengths and multicoil receiver arrays with parallel imaging. This review critically discusses models, acquisition, and postprocessing approaches that are currently available for DT MR imaging, as well as their limitations and possible improvements, to provide a better understanding of the strengths and weaknesses of this technique and a background for designing diffusion studies in MS. PMID- 17353306 TI - Image quality of multisection CT of the brain: thickly collimated sequential scanning versus thinly collimated spiral scanning with image combining. AB - BACKGROUND AND PURPOSE: Routine CT of the brain is traditionally performed with sequential CT. We assessed whether sequential CT can be replaced with thinly collimated multisection spiral CT without loss of image quality. MATERIALS AND METHODS: An observer study was conducted using data from 23 patients who were scanned with both a sequential (collimation, 4 x 5 mm) and a spiral technique (collimation, 4 x 1 mm; pitch, 0.875). Each sequential image was registered with 4 combined spiral CT images at 1.2 mm distance. Two neuroradiologists blindly scored 232 image pairs on 6 aspects: streak artifacts, visualization of brain tissue near skull, visualization of hypoattenuated lesions, gray/white matter differentiation, image noise, and overall image quality. A 5-point scale (range, 2 to 2) was used to score the preferences. The 23 pairs of complete scans were scored likewise. In this case, no registration was performed. RESULTS: Virtually all mean scores were positive (ie, showed a preference for the spiral technique). For the comparison of image pairs, the preferences with respect to streak artifacts (mean score, 1.36), visualization of brain tissue near the skull (mean score, 0.69), and overall image quality (mean score, 0.95) were significant (P < .001). With respect to visualization of hypo-attenuated lesions, image noise, and gray/white matter differentiation (mean scores, 0.18, 0.27, and 0.13), the preferences for spiral CT were not significant. The preferences for the spiral technique were also present at the comparison of the complete scans. CONCLUSION: Thinly collimated multisection spiral CT of the brain with image combining is superior to thickly collimated sequential CT. PMID- 17353307 TI - Effect of training and experience on qualitative and quantitative CT perfusion data. AB - BACKGROUND AND PURPOSE: To evaluate interobserver reliability of obtaining CT perfusion (CTP) data for qualitative identification of perfusion abnormality and quantitative assessment through regions-of-interest (ROIs) placement. MATERIALS AND METHODS: Six observers participated in the study (neuroradiology attending physician, neurology attending physician, neuroradiology fellow, radiology resident physician, senior and junior CT technologists). After a brief training session, each observer evaluated 20 CTP datasets for qualitative identification of a right- or left-sided perfusion abnormality or symmetric perfusion. Observers also placed a single ROI of standard size to obtain quantitative data on the most severely hypoperfused region. An additional 10 ROIs were placed on the cortex to quantitatively evaluate global cortical perfusion. Mean quantitative cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) values were analyzed. RESULTS: The kappa values for qualitative assessment of a perfusion abnormality ranged from 0.55 to 1.0. Coefficients of variation for quantitative assessment of ischemia/infarct region were 27.10% for CBF, 13.33% for CBV, and 4.66% for MTT. Coefficients of variation for quantitative assessment of global cortical perfusion were 11.88% for CBF, 13.66% for CBV, and 3.55% for MTT. The junior CT technologist and neuroradiology fellow showed significant differences compared with other observers for the ischemia/infarct region and global cortical perfusion, respectively. CONCLUSION: Overall, quantitative differences seen in this study would not necessarily affect quality of interpretation of ischemia/infarct region or global cortical perfusion. Therefore, obtaining qualitative and quantitative CTP data can reliably be performed in the clinical setting among observers with various levels of skill and experience when using a uniform and standard technique. PMID- 17353308 TI - In vivo assessment and visualization of intracranial arterial hemodynamics with flow-sensitized 4D MR imaging at 3T. AB - SUMMARY: We evaluated electrocardiogram-synchronized flow-sensitized 4 dimensional MR imaging at 3T in combination with advanced 3D visualization strategies to ascertain its feasibility for the assessment of local intracranial blood-flow patterns in vivo. In large arteries of healthy volunteers, the temporal and spatial evolution of blood flow was successfully visualized and revealed--for example, a helical flow pattern in the carotid siphon. In a patient with steno-occlusive neurovascular disease, stagnant and retrograde flow patterns were readily visible. PMID- 17353309 TI - Detection of intracranial atherosclerotic steno-occlusive disease with 3D time-of flight magnetic resonance angiography with sensitivity encoding at 3T. AB - BACKGROUND AND PURPOSE: The spatial resolution of 3D time-of-flight MR angiography (TOF-MRA) can be improved within a reasonable examination time by combining 3T and sensitivity encoding technique. We evaluated the diagnostic performance of high-resolution 3D TOF-MRA at 3T in patients with suspected atherosclerotic steno-occlusive disease of the intracranial arteries. MATERIALS AND METHODS: We assessed 160 arteries in 39 patients: 68 distal internal carotid arteries, 68 middle cerebral arteries, and 24 vertebrobasilar arteries. The measured voxel size of 3D TOF-MRA was 0.28 x 0.56 x 1.2 mm(3). Steno-occlusive disease was assessed independently by 2 observers using conventional angiography as the reference standard. RESULTS: According to observers 1 and 2, respectively, 3D TOF-MRA at 3T had a sensitivity of 78%/85% (21/27, 23/27), a specificity of 95%/95% (126/133, 127/133), a positive predictive value of 75%/79% (21/28, 23/29), and a negative predictive value of 95%/97% (126/132, 127/131), using a 50%-99% threshold of diameter stenosis. For detection of complete occlusion, according to observers 1 and 2, respectively, 3D TOF-MRA at 3T had a sensitivity of 100% (13/13), a specificity of 99% (145/147), a positive predictive value of 87% (13/15), and a negative predictive value of 100% (145/145). Interobserver agreement of 3D TOF-MRA was excellent (kappa = 0.81). CONCLUSION: High-resolution 3D TOF-MRA with sensitivity encoding at 3T can be used as a reliable diagnostic tool for the detection of clinically significant steno-occlusive disease of major intracranial arteries. PMID- 17353310 TI - MR regional perfusion imaging: visualizing functional collateral circulation. AB - SUMMARY: We applied regional perfusion imaging (RPI), a new arterial spin labeling MR imaging method that selectively studies regions of the brain perfused by individual carotid and basilar arteries. In a patient with cerebrovascular disease, RPI showed cerebral tissue perfused by pial collateral vessels, thereby demonstrating the relationship between anatomic and functional information, which was lacking in conventional x-ray angiography. RPI may be useful to study functional collateral circulation and hence guide therapy in ischemic disease. PMID- 17353311 TI - Multimodal coregistration in patients with temporal lobe epilepsy--results of different imaging modalities in lateralization of the affected hemisphere in MR imaging positive and negative subgroups. AB - BACKGROUND AND PURPOSE: In this study, intensive video electroencephalogram (EEG) monitoring, high-resolution MR imaging (MR imaging), proton MR spectroscopy ((1)H MR spectroscopy) and single-photon emission CT (SPECT) were compared in patients with temporal lobe epilepsy (TLE) to evaluate lateralization of affected hemisphere with regard to bilateral affection and postoperative outcome. PATIENTS AND METHODS: Recall ratio of each technique for indicating the affected hemisphere was determined in 49 patients with TLE. Postoperative outcome was established by Engel classification. RESULTS: Twenty-two of 25 patients with TLE with evidence for hippocampal sclerosis in MR imaging (MR imaging-positive) were graded as unilateral by EEG findings whereas 3 were classified as bilateral. Fourteen of 24 MR imaging-negative patients were graded as unilateral by EEG and 10 as bitemporal. (1)H-MR spectroscopy indicated concordant lateralization to EEG in 82% of MR imaging-positive patients and 71% of MR imaging-negative patients and to SPECT in 84% of MR imaging-positive patients and 67% of MR imaging negative patients with TLE. In unilateral TLE, the concordance rate of both modalities was 74% in MR imaging-positive patients and 67% in MR imaging-negative patients. Contralateral findings to EEG focus were found in 28% by (1)H-MR spectroscopy and in 27% by SPECT. Concordant findings to the operated side of different modalities revealed a clear tendency (P = .08) for a better postoperative outcome compared with bitemporal or contralateral findings. CONCLUSION: Our data demonstrate that multimodal imaging in patients with TLE improves lateralization of affected hemispheres, especially in patients without pathologic findings in MR imaging, and indicates bilateral effect, which is important to identify patients who will benefit from surgery. PMID- 17353312 TI - Stereotactic comparison among cerebral blood volume, methionine uptake, and histopathology in brain glioma. AB - BACKGROUND AND PURPOSE: Vascularity, metabolism, and histologic grade are related in gliomas but the exact determinants of these relationships are not fully defined. We used image coregistration and stereotactic biopsies to regionally compare cerebral blood volume (CBV) and (11)C-methionine (MET) uptake measurements in brain gliomas and to assess their relationship by histopathologic examination. MATERIALS AND METHODS: Fourteen patients with brain gliomas underwent MR imaging, including dynamic susceptibility contrast-enhanced MR and positron-emission tomography (PET) using MET acquired in identical stereotactic conditions before biopsy. MR-based CBV maps were calculated and both CBV maps and PET images were coregistered to anatomic images. Sixty-five biopsy samples were obtained on trajectories targeted toward high MET uptake area. The following histopathologic features were semiquantified in each sample: mitotic activity, endothelial proliferation, cellular pleomorphism, and tumor necrosis. CBV and MET uptake values were measured in the biopsy area and normalized to contralateral white matter. CBV ratios were compared with MET uptake ratios, and both measurements were compared with histologic features of each sample. RESULTS: CBV ratios ranged from 0.08 to 10.24 (median = 1.73), and MET uptake ratios ranged from 0.30 to 4.91 (median = 1.67). There was a positive correlation between CBV ratios and MET uptake ratios (r = 0.65, P < .001). Both CBV and MET uptake ratios were found to be significantly related to endothelial proliferation and mitotic activity (P < .01). CONCLUSION: Within glial tumors, there is a local relationship between CBV and MET uptake measurements. Both provide indices of focal malignant activity. PMID- 17353313 TI - Changes in fiber integrity, diffusivity, and metabolism of the pyramidal tract adjacent to gliomas: a quantitative diffusion tensor fiber tracking and MR spectroscopic imaging study. AB - BACKGROUND AND PURPOSE: The underlying changes in the neuronal connectivity adjacent to brain tumors cannot always be depicted by conventional MR imaging. The hypothesis of this study was that preoperative sensorimotor deficits are associated with impairment in pyramidal fiber bundles. Hence, we investigated the potential of combined quantitative diffusion tensor (DT) fiber tracking and MR spectroscopic imaging (MRSI) to determine changes in the pyramidal tract adjacent to gliomas. MATERIALS AND METHODS: Quantitative DT fiber tracking and proton MRSI were performed in 20 patients with gliomas with WHO grades II-IV. Eight patients experienced preoperative sensorimotor deficits. Mean diffusivity (MD), fractional anisotropy (FA), and number of fibers per voxel (FpV) were calculated for the pyramidal tract of the ipsilateral and contralateral hemisphere. Metabolite concentrations for choline-containing compounds (Cho), creatine (Cr), and N acetylaspartate (NAA) were computed, using LCModel, for all voxels located at the pyramidal tracts. RESULTS: For the whole pyramidal tract, quantitative DT fiber tracking resulted in significantly lower FpV and FA values (P < .001), but not MD values, for the ipsilateral hemisphere. For the section of the fiber bundle closest to the lesion, we found significantly decreased FpV and FA (P < .001) and increased MD (P = .002). MRSI showed, for the same volumes of interest, significantly decreased NAA (P = .001), increased Cho (P = .034) and Cho/NAA (P = .001) for the ipsilateral pyramidal tract. In patients suffering sensorimotor deficits, we found significantly lower FA (P = .022) and higher MD values (P = .026) and a strongly negative correlation between FA and MD (R = -0.710, P = .024) but no correlation in patients without deficits (R = 0.078, ns). CONCLUSION: Quantitative DTI was able to show significant differences in diffusivity of the pyramidal tract in patients with sensorimotor deficits in relation to patients without them. The additional use of proton MRSI may be helpful to discern whether these diffusivity changes in fiber tracts are caused by tumor infiltration or peritumoral edema. PMID- 17353314 TI - Prefrontal N-acetylaspartate and poststroke recovery: a longitudinal proton spectroscopy study. AB - BACKGROUND AND PURPOSE: Functional imaging studies suggest that poststroke recovery is related to the reorganization in both contralesional and ipsilesional prefrontal cortex. Little is known, however, about how longitudinal metabolic changes in prefrontal regions relate to the improvement after stroke. We sought to determine whether poststroke recovery is associated with changes in N acetylaspartate/creatine (NAA/Cr) ratio within contralesional prefrontal regions. MATERIALS AND METHODS: Twenty-seven patients with a first ischemic stroke located outside the frontal lobes were included. Proton MR spectroscopy ((1)H-MRS) was performed on a 1.5T scanner. Point-resolved spectroscopy sequence (PRESS) was used. NAA/Cr was measured both in ipsilesional and contralesional prefrontal regions in early (14 +/- 6 days after stroke) and chronic phases of the disease (110 +/- 30 days after). Patients' neurologic status was assessed using Scandinavian Stroke Scale (SSS) at discharge from the stroke unit and during second (1)H-MRS examination. RESULTS: Subjects showing increased contralesional NAA/Cr from first to follow-up examination improved significantly more on the SSS than patients not showing this increase. Analysis was performed while correcting for change in NAA/Cr levels in the ipsilesional hemisphere. For the whole group, the change in contralesional NAA/Cr was significantly correlated to the change in SSS scores (r = 0.40, P = .03). Change in the ipsilesional NAA/Cr measures did not correlate with the change in SSS scores. CONCLUSION: Poststroke recovery was related to the increase in contralesional prefrontal NAA/Cr. This association may reflect recovery mechanisms involving the nonaffected hemisphere. Further assessment of these regions may provide information about mechanisms contributing to neurologic improvement. PMID- 17353315 TI - A diffusion longitudinal MR imaging study in normal-appearing white matter in untreated relapsing-remitting multiple sclerosis. AB - BACKGROUND AND PURPOSE: Our aim was to evaluate the hypothesis that water diffusion alterations are present in normal-appearing white matter of patients with relapsing-remitting multiple sclerosis (RRMS) and to assess their change with time. MATERIALS AND METHODS: Fifty-four subjects with clinically diagnosed RRMS, with disease duration of less than 12 months and an expanded disability status scale (EDSS) score of <3.5, underwent a diffusion 3T MR imaging study. The apparent diffusion coefficient (ADC) maps generated were compared with those of 18 control subjects. Eighteen of the 54 patients underwent MR imaging assessment at 3 and 6 months after baseline evaluation. Remitting patients were clinically and MR imaging stable for the 2 months before the study. All patients were drug free for the 3 months before the study, and in the relapsing patients, the MR imaging was always performed before beginning treatment. RESULTS: Mean ADC values showed significant differences when relapsing, remitting, and control patients were compared. The relapsing or remitting phase showed significant difference when compared both with controls (P < .01) and between them (P < .05). Comparing mean ADC values of patients with clinical disability (EDSS <2 versus EDSS >/=2) also provided significant differences with the control group (P < .01). The data of patients showing a relapsing episode during the longitudinal part of the study showed a significant difference compared with data from their remitting phase (P < .01). CONCLUSION: Brain microstructural changes can be detected and correlate with clinical impairment during the stages of MS. These changes modify with time in the relapsing group. PMID- 17353316 TI - Whole-brain histogram and voxel-based analyses of apparent diffusion coefficient and magnetization transfer ratio in celiac disease, epilepsy, and cerebral calcifications syndrome. AB - BACKGROUND AND PURPOSE: Diffusion and magnetization transfer (MT) techniques have been applied to the investigation with MR of epilepsy and have revealed changes in patients with or without abnormalities on MR imaging. We hypothesized that also in the coeliac disease (CD), epilepsy and cerebral calcifications (CEC) syndrome diffusion and MT techniques could reveal brain abnormalities undetected by MR imaging and tentatively correlated to epilepsy. MATERIALS AND METHODS: Diffusion and MT weighted images were obtained in 10 patients with CEC, 8 patients with CD without epilepsy and 17 healthy volunteers. The whole brain apparent diffusion coefficient (ADC) and MT ratio (MTR) maps were analyzed with histograms and the Statistical Parametric Mapping 2 (SPM2) software. We employed the non-parametric Mann-Whitney U test to assess differences for ADC and MTR histogram metrics. Voxel by voxel comparison of the ADC and MTR maps was performed with 2 tails t-test corrected for multiple comparison. RESULTS: A significantly higher whole brain ADC value as compared to healthy controls was observed in CEC (P = 0.006) and CD (P = 0.01) patients. SPM2 showed bilateral areas of significantly decreased MTR in the parietal and temporal subcortical white matter (WM) in the CEC patients. CONCLUSION: Our study indicates that diffusion and MT techniques are also capable of revealing abnormalities undetected by MR imaging. In particular patients with CEC syndrome show an increase of the whole brain ADC histogram which is more pronounced than in patients with gluten intolerance. IN CEC patients, voxel-based analysis demonstrates a localized decrease of the MTR in the parieto-temporal subcortical WM. PMID- 17353317 TI - Morphometry and 1H-MR spectroscopy of the brain stem and cerebellum in three patients with fragile X-associated tremor/ataxia syndrome. AB - SUMMARY: Morphometry and spectroscopy were performed in 3 patients with fragile X associated tremor/ataxia syndrome (FXTAS). The brain stem and cerebellum were atrophic and satisfied criteria for olivopontocerebellar atrophy in 2 patients. However, the vermis was relatively spared and the basis pontis maintained its oval shape. The only spectroscopic abnormality was a decrease of the pontine N acetylaspartate/creatine ratio in 1 patient. Atrophy and metabolic changes in FXTAS differ to some extent from those of olivopontocerebellar atrophy. PMID- 17353318 TI - Acute optic nerve infarction demonstrated by diffusion-weighted imaging in a case of rhinocerebral mucormycosis. AB - SUMMARY: A 60-year-old woman developed right-eye vision loss secondary to rhinocerebral mucormycosis. Routine MR imaging sequences including enhanced MR imaging showed normal optic nerves, but a diffusion-weighted sequence and apparent diffusion coefficient maps revealed markedly restricted diffusion in the right optic nerve. This MR imaging abnormality of optic nerve infarction due to mucormycosis has not been reported previously. PMID- 17353319 TI - Bilateral orbital lymphangiomas in two patients with generalized lymphangiomatosis. AB - SUMMARY: Generalized lymphangiomatosis is a rare congenital malformation of the lymphatics, characterized by cystic lesions in parenchymal organs and lytic bone lesions. In this report, we describe the radiographic and clinical features of 2 unusual cases of generalized lymphangiomatosis with bilateral orbital involvement. PMID- 17353320 TI - Tuberculous otomastoiditis on high-resolution temporal bone CT: comparison with nontuberculous otomastoiditis with and without cholesteatoma. AB - BACKGROUND AND PURPOSE: Our purpose was to evaluate the differential findings of tuberculous otomastoiditis (TOM) and nontuberculous chronic otomastoiditis with or without middle ear cholesteatoma on high-resolution CT of the temporal bone. MATERIALS AND METHODS: We reviewed 19 cases of TOM, 30 cases of chronic otomastoiditis (COM), and 30 cases of COM with cholesteatoma (CHOM), all of which had been confirmed by pathologic examination after surgery or middle ear mucosal biopsy. Two neuroradiologists analyzed the findings of temporal bone CT. RESULTS: The soft tissue attenuation in the entire middle ear cavity, preservation of the mastoid air cells without sclerotic change, and soft tissue extension to the external auditory canal (EAC) or mucosal thickening of the bony EAC, had statistical significance (chi(2) test, P < .05) between the TOM group and the COM group and between the TOM group and the CHOM group. Erosion of the ossicles and scutum was statistically significant (chi(2) test, P < .05) between the TOM group and the CHOM group. CONCLUSION: Findings of soft tissue in the entire middle ear cavity, preservation of mastoid air cells without sclerotic change, soft tissue extension, or mucosal thickening of the EAC with intact scutum seemed to be helpful in differentiating TOM from COM and CHOM. PMID- 17353321 TI - Observer agreement in the assessment of endovascular aneurysm therapy and aneurysm recurrence. AB - BACKGROUND AND PURPOSE: Assessments of completeness of endovascular cerebral aneurysm therapy are commonly reported in the literature. We studied several aneurysm assessment scales with regard to observer variability, which directly affects validity of these scales. MATERIALS AND METHODS: Initial aneurysm occlusion and occlusion at a follow-up angiogram at 3-6 months were assessed independently by 2 experienced observers. Assessments of each aneurysm were made using 3 different scales: 4-response (complete, dog ear, neck remnant, incomplete), 3-response (complete, near-complete, incomplete), and 2-response (complete or near-complete, incomplete). Assessments were also made of comparisons of initial treatment angiogram with follow-up angiogram using 2 different scales: 3-response (better, same, worse) and 2-point response (not worse, worse). RESULTS: With assessments of both initial and follow-up angiograms, interobserver and intraobserver agreement was progressively worse with increasing response choices in the scales. Observer agreement on assessments of initial angiograms (kappa values 0.48-0.67) was worse than that for follow-up angiograms (kappa values 0.66-0.97). For the comparisons of the initial angiogram with the follow-up angiogram, there was worse observer agreement with the 3 response scale (kappa values 0.64-0.71) than with the 2-response scale (kappa values 0.78-0.89). CONCLUSION: Interobserver and intraobserver variability are inherent to assessment scales of completeness of cerebral aneurysm therapy. Observer variability is substantially better in scales that offer fewer observer responses. However, scales with fewer observer responses may not identify aneurysm subgroups that have differing risks of recurrence and/or rehemorrhage. PMID- 17353322 TI - Scales, agreement, outcome measures, and progress in aneurysm therapy. PMID- 17353323 TI - A study on maximum skin dose in cerebral embolization procedures. AB - BACKGROUND AND PURPOSE: It is essential to measure the skin dose of radiation received by patients during interventional neuroradiologic procedures performed under fluoroscopic guidance, such as embolization of cerebral aneurysms, which is regarded as a high-dose interventional radiology procedure. In this study, we report a method for evaluating maximum skin dose (MSD), an ideal marker of radiation-induced effects, based on an innovative use of radiochromic films. MATERIALS AND METHODS: Forty-eight procedures were studied in 42 patients undergoing embolization of cerebral aneurysms. Fluoroscopic and digital dose-area product (DAP), fluoroscopy time, and total number of acquired images were recorded for all procedures. The MSD was measured using Gafchromic XR type R films. RESULTS: The MSD was measured in one group of 21 procedures. The coefficient (kappa) of the interpolation line between the skin dose and the DAP (kappa = 0.0029 cm(-2)) was determined. An approximate value of MSD from the DAP for the remaining 27 procedures was estimated by means of an interpolation line. The mean MSD was found to be 1.16 Gy (range, 0.23-3.20 Gy). CONCLUSION: The use of radiochromic XR type R films was shown to be an effective method for measuring MSD. These films have the advantage of supplying information on both the maximum dose and the distribution of the dose: this satisfies the most stringent interpretation of Food and Drug Administration, American College of Radiology, and international recommendations for recording skin dose. PMID- 17353324 TI - Long-term 3T MR angiography follow-up after therapeutic occlusion of the internal carotid artery to detect possible de novo aneurysm formation. AB - BACKGROUND AND PURPOSE: The purpose of this study was to assess the incidence of de novo aneurysm formation, the incidence of subarachnoid hemorrhage (SAH), and the growth of existing untreated aneurysms in 52 patients after therapeutic carotid artery balloon occlusion for carotid aneurysms. PATIENTS AND METHODS: Between January 1996 and August 2004, 52 patients were treated with carotid artery balloon occlusion for carotid aneurysms. In June 2005, all patients, their next of kin, or family physicians were contacted and questioned concerning episodes of headache or hospital admissions that could be attributed to SAH. In addition, MR imaging and MR angiography (MRA) at 3T were performed in 26 of 44 surviving patients after a mean follow-up period of 50.2 months (median, 43.5 months; range, 14-107 months). MR imaging and MRA studies were compared with the digital subtraction angiograms at the time of carotid artery occlusion. RESULTS: During clinical follow-up of 52 patients at a mean of 50.3 months (median, 42.5 months; range, 0-107 months), no episodes of SAH were reported (0%; 97.5% confidence interval [CI], 0-8.2%). In the 26 patients with follow-up MR imaging, no de novo aneurysms were detected (0%; 97.5 CI, 0-13.2%). Five existing untreated small aneurysms in 5 patients had not enlarged after a mean follow-up of 40 months. CONCLUSION: In this study, therapeutic carotid artery occlusion was not associated with development of new aneurysms or enlargement of existing untreated aneurysms with time. PMID- 17353325 TI - Aseptic meningitis after embolization of cerebral aneurysms using hydrogel-coated coils: report of three cases. AB - SUMMARY: We report the development of aseptic meningitis in 3 patients with aneurysms treated with hydrogel-coated coils. Patients presented with febrile meningeal syndromes during the 24 hours following the procedures and responded to corticosteroids. One of them developed delayed hydrocephalus that required treatment with a ventriculoperitoneal shunt. Aseptic meningitis is one of the important complications related to hydrogel-coated coils that should be recognized. More information based on the posttreatment surveillance after use of hydrogel-coated coils is required. PMID- 17353326 TI - Balloon catheter disruption of middle cerebral artery thrombus in conjunction with thrombolysis for the treatment of acute middle cerebral artery embolism. AB - BACKGROUND AND PURPOSE: The goal of this study was to prospectively assess the feasibility, safety, and efficacy of balloon disruption of the middle cerebral artery (MCA) by using a deflated balloon catheter combined with an intra-arterial thrombolysis for the treatment of acute ischemic stroke. MATERIALS AND METHODS: Seven consecutive patients with clinical findings of acute major-vessel stroke met our criteria and underwent balloon disruption of an MCA thrombus with a deflated balloon catheter. The balloon disruption was performed with a low profile microballoon catheter. The microballoon was inflated in the distal carotid artery and then deflated and advanced just distal to the occlusion site in the MCA. Thereafter, an intra-arterial thrombolysis of the MCA was applied. The maximum time from the onset of symptoms to the start of treatment and maximum dosage of urokinase was 6 hours and 600,000 U. The outcome was classified as good for a modified Rankin Scale (mRS) score of 0 or 1, moderate for a score of 2 or 3, and poor for a score of 4 or 5. RESULTS: Complete recanalization was achieved in 5 patients and partial recanalization in 3. Three patients recovered to an mRS score of 0 or 1; 3, to scores of 2 or 3; and 1, to a score of 4. No patients died. There was no major intracerebral hemorrhage. CONCLUSIONS: The penetration of the MCA with a deflated balloon catheter combined with an intra-arterial thrombolysis may be a safe and effective treatment for acute ischemic stroke. PMID- 17353327 TI - Nidal embolization of brain arteriovenous malformations using Onyx in 94 patients. AB - BACKGROUND AND PURPOSE: To report our experience in the treatment of brain arteriovenous malformations (BAVMs) using Onyx (ev3, Irvine, Calif). PATIENTS AND METHODS: From January 1999 to October 2004, 94 patients with BAVMs were treated endovascularly in our department. They were 51 (54%) men and 43 (46%) women with a mean age of 32 years. A total of 210 endovascular procedures were performed with Onyx as the sole embolic agent in 88 procedures; Onyx and n-butyl cyanoacrylate (n-BCA) were used in combination in 50 procedures, and n-BCA alone was used in 72 procedures. RESULTS: The course of endovascular treatment was completed in 53 patients. In 26 patients (49%, 26/53) an angiographic cure was achieved using embolization as the sole therapeutic technique. Seven (13%, 7/53) patients underwent a surgical resection of the residual BAVM nidus, 20 (38%, 20/53) patients underwent radiosurgical treatment after nidal size reduction <2 cm was accomplished by endovascular treatment. Further endovascular treatment was planned in 33 patients, whereas in 5 patients, the continuation of embolization was aborted due to difficult nidus catheterization. Procedure-related permanent neurologic deficits were observed in 8 (8.5%, 8/94) patients. There were 3 procedure-related deaths. CONCLUSION: Onyx is suitable for brain BAVM embolizations and allows obtaining higher rates of anatomic cures compared with those obtained previously with other embolic agents. PMID- 17353328 TI - Inter- and intraobserver variability in the assessment of brain arteriovenous malformation angioarchitecture and endovascular treatment results. AB - BACKGROUND AND PURPOSE: Several angiographic features of brain arteriovenous malformations (BAVMs) have been associated with an increased risk of hemorrhage. However, interpretation of these features may not be consistent between observers. We conducted a study to determine inter- and intraobserver agreement of various angioarchitectural characteristics of BAVM. MATERIALS AND METHODS: Two experienced interventional neuroradiologists independently reviewed pre- and post endovascular treatment angiograms from 50 consecutive patients. Axial CT and/or MR images before treatment were included. We collected the following data: Spetzler-Martin grades, number of involved arterial territories, associated aneurysms by location (circle of Willis, feeding artery, intranidal, and venous), and nidus reduction after endovascular treatment (<33%, 33%-66%, and >66%). The reviewers were compared with each other, and 1 was compared with himself after a 3-month interval. Measures of agreement were performed by using the kappa statistic (kappa) for nominal data and the weighted kappa for ordinal data. RESULTS: Inter- and intraobserver agreement were higher for assessment of the Spetzler-Martin grade (weighted kappa = 0.70/0.75) and nidus size reduction after endovascular treatment (kappa = 0.74/0.77). Inter- and intraobserver agreement were inferior for findings concerning feeding artery aneurysms (kappa = 0.19/0.36), intranidal aneurysms (kappa = 0.34/0.35), and venous aneurysms (kappa = 0.50/0.67). CONCLUSION: Angiographic characteristics of BAVMs considered as risk factors for hemorrhage, such as aneurysms, are not reliably detected on global angiograms between different observers. In contrast, the Spetzler-Martin grading system and angiographic results of endovascular treatment can be used with high observer agreement. PMID- 17353329 TI - Percutaneous direct puncture glue embolization of high-flow craniofacial arteriovenous lesions: a new circular ring compression device with a beveled edge. AB - SUMMARY: The purpose of this study was to evaluate the efficacy of a newly designed circular ring compression device that allows safe and effective glue injection during preoperative embolization of high-flow superficial craniofacial arteriovenous malformations (AVMs). The device was used in 4 cases of craniofacial AVM with multiple feeding arteries and draining veins. It provided a safe glue injection route as well as effective compression of radiating multiple venous drainage routes. PMID- 17353330 TI - Natural history of the canine vein pouch aneurysm model. AB - BACKGROUND AND PURPOSE: The canine vein pouch aneurysm model is widely used for testing and development of devices directed at the endovascular treatment of aneurysms. Our purpose was to determine the incidence of spontaneous thrombosis and rupture of these aneurysms. MATERIALS AND METHODS: A retrospective review of laboratory records of canine vein pouch aneurysms made during a 6-year period was performed. The aneurysm and parent artery dimensions as well as incidences of spontaneous thrombosis and rupture were noted. RESULTS: During the interval studied, 326 vein patch aneurysms were made in 310 canines. Of these, 102 were sidewall (lateral) and 224 were bifurcation aneurysms. Spontaneous occlusion occurred in 9 of the sidewall aneurysms and in only 1 of the bifurcation aneurysms. None of the aneurysms ruptured. CONCLUSION: Spontaneous occlusion of the sidewall canine vein patch aneurysm occurred less than 10% of the time; in the bifurcation aneurysms, it almost never occurred. These characteristics enhance the value of this model for use in testing of devices intended for the endovascular treatment of aneurysms. PMID- 17353331 TI - Use of self-expanding stents in distal small cerebral vessels. AB - BACKGROUND: Previously, endovascular treatment of wide-necked aneurysms and stenosis involving small vessels measuring <2 mm in diameter was limited. There are no reports in the literature addressing stent placement in small distal cerebral vessels. Recent experience with the Neuroform stent has shown that this device can be safely and effectively used to treat aneurysms in vessels of this caliber. MATERIALS AND METHODS: We report 8 cases of Neuroform stent placement into cerebral vessels measuring <2 mm in diameter (range, 1.1-1.8 mm). All stents were placed for aneurysm treatment in conjunction with coiling. Lesion locations and number were as follows: anterior communicating artery region (n = 5), pericallosal artery A2-A3 (n = 1), middle cerebral artery (MCA) M1-M2 (n = 1), and MCA M3-M4 (n = 1). Clinical follow-up ranged from 4.5 to 18 months. Imaging follow-up was performed with MR imaging/MR angiography. RESULTS: All procedures were successfully performed without immediate or delayed device-related complications. Intraprocedural thrombus developed within the stent in 2 patients and immediately resolved with 10 mg of intra-arterial abciximab. Follow-up at 18 months demonstrated durable results. There were no clinical neurologic symptoms related to the treated vessel territory at follow-up. CONCLUSION: Development of newer low-profile endovascular devices allows access and ability to treat lesions farther out in the smaller cerebral vessels. We have safely and successfully treated 8 vessels smaller than 2 mm in diameter with newer self-expanding stents with good short- and intermediate-term results. Further follow-up and more experience are necessary to determine long-term results. PMID- 17353332 TI - cerebellar atrophy after moderate-to-severe pediatric traumatic brain injury. AB - BACKGROUND AND PURPOSE: Although the cerebellum has not attracted the same degree of attention as cortical areas and the hippocampus in traumatic brain injury (TBI) literature, there is limited structural and functional imaging evidence that the cerebellum is also vulnerable to insult. The cerebellum is emerging as part of a frontocerebellar system that, when disrupted, results in significant cognitive and behavioral consequences. We hypothesized that cerebellar volume would be reduced in children following TBI and wished to examine the relation between the cerebellum and known sites of projection, including the prefrontal cortex, thalamus, and pons. MATERIALS AND METHODS: Quantitative MR imaging was used to measure cerebellar white and gray matter and lesion volumes 1-10 years following TBI in 16 children 9-16 years of age and 16 demographically matched typically developing children 9-16 years of age. Cerebellar volumes were also compared with volumetric data from other brain regions to which the cerebellum projects. RESULTS: A significant group difference was found in cerebellar white and gray matter volume, with children in the TBI group consistently exhibiting smaller volumes. Repeating the analysis after excluding children with focal cerebellar lesions revealed that significant group differences still remained for cerebellar white matter (WM). We also found a relation between the cerebellum and projection areas, including the dorsolateral prefrontal cortex, thalamus, and pons in 1 or both groups. CONCLUSION: Our finding of reduced cerebellar WM volume in children with TBI is consistent with evidence from experimental studies suggesting that the cerebellum and its related projection areas are highly vulnerable to fiber degeneration following traumatic insult. PMID- 17353333 TI - Characterizing anatomic differences in boys with attention-deficit/hyperactivity disorder with the use of deformation-based morphometry. AB - BACKGROUND AND PURPOSE: Most previous neuroimaging studies of attention deficit/hyperactivity disorder (ADHD) rely on the manual delineation of the region of interest, which is subjective and lacks reproducibility. The purpose of this study was to use an automated method to assess whether there are abnormalities in the brains of patients with ADHD. In view of findings from previous imaging and neuropsychologic studies, we predicted that we would detect abnormalities in many brain regions of patients with ADHD. MATERIALS AND METHODS: Twelve boys with ADHD and 12 control subjects underwent MR imaging assessments. Statistically significant changes in regional volume were analyzed by using deformation based morphometry (DBM). This technique derived a voxel-wise estimation of regional tissue volume change from the deformation field required to warp subject to the template image. Morphologic differences between groups were estimated at each voxel, applying a threshold (P < .001) to the resulting voxel statistic maps to generate clusters of spatially contiguous suprathreshold voxels, RESULTS: The statistical results reveal some pronounced volume alterations in the brains of ADHD. Volume reductions are mainly localized in right prefrontal (Talairach 48, 20, 31), right medial temporal (Talairach 59, 52, 13), left parietal lobe (Talairach -32, -61, 41), and right basal ganglia (especially right putamen) (Talairach 21, 1, 11); the regions of volume enlargement in the brains of ADHD are observed in the right occipital lobe (Talairach 20, -86, 29) and in the left posterior lateral ventricle (Talairach 23, -40, 15). CONCLUSION: Our findings confirm that there are widespread abnormalities in volume of boys with ADHD. PMID- 17353334 TI - Treatment monitoring of brain creatine deficiency syndromes: a 1H- and 31P-MR spectroscopy study. AB - BACKGROUND AND PURPOSE: Brain creatine (Cr) deficiencies (BCr-d) are rare disorders of creatine biosynthesis and transport. We performed consecutive measures of total Cr (tCr) and of its phosphorylated fraction, phosphocreatine (PCr), in the brains of children affected by Cr synthesis defects during a long period of therapy. The aim was to identify the optimal treatment strategy for these disorders. MATERIALS AND METHODS: Two patients with guanidinoacetate methyltransferase defect (GAMT-d) were treated with different amounts of Cr and with diet restrictions aimed at reducing endogenous guanidinoacetate (GAA) synthesis. Three patients with arginine:glycine amidinotransferase defect (AGAT d) were treated with different Cr intakes. The patients' treatments were monitored by means of (1)H- and (31)P-MR spectroscopy. RESULTS: Cr and PCr replenishment was lower in GAMT-d than in AGAT-d even when GAMT-d therapy was carried out with a very high Cr intake. Cr and especially PCr replenishment became more efficient only when GAA blood values were reduced. Adenosine triphosphate (ATP) was increased in the baseline phosphorous spectrum of GAMT-d, and it returned to a normal value with treatment. Brain pH and brain P(i) showed no significant change in the AGAT-d syndrome and at any Cr intake. However, 1 of the 2 GAMT-d patients manifested a lower brain pH level while consuming the GAA lowering diet. CONCLUSIONS: AGAT-d treatment needs lower Cr intake than GAMT-d. Cr supplementation in GAMT-d treatment should include diet restrictions aimed at reducing GAA concentration in body fluids. (1)H- and especially (31)P-MR spectroscopy are the ideal tools for monitoring the therapy response to these disorders. PMID- 17353335 TI - Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study. AB - PURPOSE: To prospectively assess the short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures (VCF) treated with percutaneous vertebroplasty (PV) compared with optimal pain medication (OPM). METHODS: Randomization of patients in 2 groups: treatment by PV or OPM. After 2 weeks, patients from the OPM arm could change therapy to PV. Patients were evaluated 1 day and 2 weeks after treatment. Visual analog score (VAS) for pain and analgesic use were assessed before, and 1 day and 2 weeks after start of treatment. Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) and Roland-Morris Disability (RMD) questionnaire scores were assessed before and 2 weeks after start of treatment. Follow-up scores in patients requesting PV treatment after 2 weeks OPM treatment were compared with scores during their OPM period. RESULTS: Eighteen patients treated with PV compared with 16 patients treated with OPM had significantly better VAS and used less analgesics 1 day after treatment. Two weeks after treatment, the mean VAS was less but not significantly different in patients treated with OPM, whereas these patients used significantly less analgesics and had better QUALEFFO and RMD scores. Scores in the PV arm were influenced by occurrence of new VCF in 2 patients. After 2 weeks OPM, 14 patients requested PV treatment. All scores, 1 day and 2 weeks after PV, were significantly better compared with scores during conservative treatment. CONCLUSION: Pain relief and improvement of mobility, function, and stature after PV is immediate and significantly better in the short term compared with OPM treatment. PMID- 17353336 TI - VERTOS: A Step in the Right Direction. PMID- 17353337 TI - Outcomes of patients receiving long-term corticosteroid therapy who undergo percutaneous vertebroplasty. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine the efficacy and rate of complications in patients undergoing percutaneous vertebroplasty (PVP) for vertebral compression fractures as a result of secondary osteoporosis caused by long-term corticosteroid use compared with patients with primary osteoporosis treated with PVP. MATERIALS AND METHODS: A retrospective review of all patients undergoing PVP was conducted to identify patients who also received long-term corticosteroid therapy. Outcomes including pain, periprocedural complications, and frequency of new fractures in patients receiving corticosteroids were compared with control patients undergoing PVP for primary osteoporosis. RESULTS: Sixty-eight patients receiving long-term corticosteroid therapy underwent 79 PVP procedures. Patients treated with corticosteroids undergoing PVP were significantly younger and more likely to be male compared with control subjects. Patients receiving long-term corticosteroid treatment experienced significant pain relief immediately postprocedure and at 1 week, 1 month, 6 months, 1 year and 2 years postprocedure (P < .0001 at all time points). Patients receiving corticosteroids experienced similar decreases in pain from baseline compared with control subjects at all follow-up time points (P > .05). The complication rate for patients receiving corticosteroids was 4.4% compared with 3.4% for control subjects (P = .60). Patients on long-term corticosteroid treatment did not have an increased risk of new fractures after PVP compared with control subjects (P = .68). CONCLUSIONS: Percutaneous vertebroplasty performed for vertebral compression fractures as a result of long-term corticosteroid therapy is as safe and effective in relieving pain as PVP performed in patients with vertebral compression fractures as a result of primary osteoporosis. PMID- 17353338 TI - Effect on partial pressure of oxygen in arterial blood in percutaneous vertebroplasty. AB - BACKGROUND AND PURPOSE: The purpose of this study is to estimate the change in partial pressure of oxygen (Pao(2)) during percutaneous vertebroplasty and also to examine the factors related to the change in Pao(2). MATERIALS AND METHODS: We retrospectively reviewed preprocedural and postprocedural Pao(2) of 59 consecutive patients who underwent percutaneous vertebroplasty between November 2003 and April 2005 (11 men and 48 women; age range, 50-93; mean age, 75 years). Fifty-four patients were treated for osteoporosis-related fractures and 5 had malignant disease. Percutaneous vertebroplasty was performed in a conventional manner under local anesthetics and conscious sedation. Preprocedural and postprocedural blood drawing was performed 5 days to 30 minutes before percutaneous vertebroplasty and also at 30 minutes after the injection of bone cement. The difference between preprocedural and postprocedural data of Pao(2) was correlated with patients' age, number of treated vertebral bodies, presence of cement leakage, and presence of malignant neoplasm for each patient. RESULTS: Mean pre-Pao(2) and post-Pao(2) were 80.9 +/- 1.4 and 70.6 +/- 1.3 mm Hg (mean +/ SE) respectively (P = .0001). Using analysis of variance, there was a significant difference according to the number of vertebral bodies. There was a positive trend of decrease in Pao(2) according to the number of vertebral bodies during percutaneous vertebroplasty. Using multiple linear regression and after adjusting by preprocedural Pao(2) and other variables, the number of vertebral bodies was still highly significant. CONCLUSION: Pao(2) decreases during percutaneous vertebroplasty, and there is a correlation between the number of treated vertebral bodies and decrease in Pao(2). PMID- 17353339 TI - Osteoblastic and mixed spinal metastases: evaluation of the analgesic efficacy of percutaneous vertebroplasty. AB - PURPOSE: To determine the analgesic efficacy of percutaneous vertebroplasty in treating osteoblastic and mixed spinal metastases. MATERIALS AND METHODS: Fifty two patients underwent 59 vertebroplasty procedures for 103 painful vertebral metastases, among which 53 were pure osteoblastic and 50 were mixed (blastic and lytic). Analgesic efficacy was classified as "excellent," "good," "fair," and "poor." The patients were followed up at 1 month, 6 months, 12 months, 2 years, and 5 years. The mean follow-up period was 17 months. RESULTS: The analgesic efficacy rate was 86% at 1 month and 92% at 6 months (among which 71% of patients had "excellent" results and 21% had with "good" results). In most cases, it was stable. It was correlated with vertebral filling quality (Fisher test, P = .0932 at 1 month follow-up) but neither with filling volume (Mann-Whitney test, P = .143 at 1 month) nor with the vertebral structure, pure blastic or mixed (Fisher test, P = .784 at 1 month). There were 5 filling failures (4.7%) whose occurrence was correlated with the pure blastic structure of the vertebra (Mann-Whitney test, P = .033). Local clinical complications were observed in 5 cases (8.5%): 1 transitory radiculalgia (1.7%), 2 durable radiculalgias (3.4%), 1 cauda equina syndrome (1.7%), and 1 hemothorax (1.7%). General clinical complications were 2 pulmonary embolisms (3.4%). No patients died. The occurrence of clinical complications was not correlated with the vertebral structure (Fisher test, P = .279). CONCLUSION: Vertebroplasty for osteoblastic and mixed metastases allows, with a well-trained operator, a satisfactory anesthesia with acceptable clinical complication rates. PMID- 17353340 TI - Diffusion-weighted imaging of the spine with a non-carr-purcell-meiboom-gill single-shot fast spin-echo sequence: initial experience. AB - BACKGROUND AND PURPOSE: To prospectively evaluate the signal-to-noise ratio (SNR) improvement in diffusion-weighted imaging (DWI) of the spine with the use of a newly developed non-Carr-Purcell-Meiboom-Gill (non-CPMG) single-shot fast spin echo (SS-FSE) sequence and its effect on apparent diffusion coefficient (ADC) measurements. MATERIALS AND METHODS: Twenty-four patients were enrolled after written informed consent. DWI of the spine was obtained with an echo-planar imaging (EPI)-based sequence followed by a non-CPMG SS-FSE technique. SNR and ADC values were measured over a lesion-free vertebral corpus. A quality score was assigned for each set of images to assess the image quality. When a spinal lesion was present, contrast-to-noise ratio (CNR) and ADC were also measured. Student t tests were used for statistical analysis. RESULTS: Mean SNR values were 5.83 +/- 2.2 and 11.68 +/- 2.87 for EPI and non-CPMG SS-FSE DWI, respectively. SNR values measured in DWI using parallel imaging were found to be significantly higher (P < .01). Mean ADCs of the spine were 0.53 +/- 0.15 and 0.35 +/- 0.15 x 10(-3) mm(2)/s for EPI and non-CPMG SS-FSE DWI, respectively. Quality scores were found to be higher for the non-CPMG SS-FSE DWI technique (P < .05). Overall lesion CNR was found to be higher in DWI with non-CPMG SS-FSE. CONCLUSION: The non-CPMG SS FSE technique provides a significant improvement to current EPI-based DWI of the spine. A study including a larger number of patients is required to determine the use of this DWI sequence as a supplementary tool to conventional MR imaging for increasing diagnostic confidence in spinal pathologic conditions. PMID- 17353341 TI - Association between lumbar epidural injection and development of acute paraparesis in patients with spinal dural arteriovenous fistulas. AB - SUMMARY: We report 3 patients with previously undiagnosed spinal dural arteriovenous fistulas (SDAVFs), who developed acute paraparesis following lumbar epidural steroid injection. MR imaging demonstrated spinal cord T2 hyperintensity, edema and/or enhancement of the conus, and intradural enlarged vascular flow voids. Spinal angiography confirmed SDAVFs arising from pedicles remote from the sites of the epidural steroid injection. Fistulas were eliminated with either endovascular or combination endovascular and open surgical approaches, with subsequent partial resolution of paraparesis. PMID- 17353342 TI - Spinal arteriovenous malformations associated with Klippel-Trenaunay-Weber syndrome: a literature search and report of two cases. AB - SUMMARY: Patients with Klippel-Trenaunay-Weber syndrome present with venous varices, cutaneous capillary malformations, and tissue hypertrophy, usually involving an extremity. A small but important subset also harbors arteriovenous malformations (AVMs) of the spine. We report 2 such cases, 1 with 3 concurrent spinal arteriovenous fistulas. These cases and our review of the literature emphasize the importance of screening the spine for AVMs. In addition, it is also important to investigate for the presence of multiple spinal AVMs. PMID- 17353343 TI - Idiopathic hypertrophic spinal pachymeningitis: report of two cases with typical MR imaging findings. AB - SUMMARY: Two patients with a chronic progressive myelopathy were successfully surgically treated and idiopathic hypertrophic spinal pachymeningitis (IHSP) was found on histology. In both patients, an extensive extramedullary mass of low T2 signal with peripheral contrast enhancement was compressing the spinal cord on MR imaging. This imaging appearance in patients with chronic progressive myelopathy should suggest the diagnosis of IHSP. PMID- 17353344 TI - Atypical teratoid/rhabdoid tumor of the spine. AB - SUMMARY: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm usually seen in young children and infants. Prognosis for AT/RT is poor, with most patients dying within 1 year of presentation. AT/RT most commonly occurs intracranially. Location in the spine, though previously reported, is rare, and imaging findings have not been emphasized in the past. We present a case of AT/RT occurring in the thoracolumbar spine of a child and review available clinical and imaging findings in previously reported cases of spinal AT/RT. PMID- 17353345 TI - The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor. AB - Erythropoiesis occurs in erythroblastic islands, where developing erythroblasts closely interact with macrophages. The adhesion molecules that govern macrophage erythroblast contact have only been partially defined. Our previous work has implicated the rat ED2 antigen, which is highly expressed on the surface of macrophages in erythroblastic islands, in erythroblast binding. In particular, the monoclonal antibody ED2 was found to inhibit erythroblast binding to bone marrow macrophages. Here, we identify the ED2 antigen as the rat CD163 surface glycoprotein, a member of the group B scavenger receptor cysteine-rich (SRCR) family that has previously been shown to function as a receptor for hemoglobin haptoglobin (Hb-Hp) complexes and is believed to contribute to the clearance of free hemoglobin. CD163 transfectants and recombinant protein containing the extracellular domain of CD163 supported the adhesion of erythroblastic cells. Furthermore, we identified a 13-amino acid motif (CD163p2) corresponding to a putative interaction site within the second scavenger receptor domain of CD163 that could mediate erythroblast binding. Finally, CD163p2 promoted erythroid expansion in vitro, suggesting that it enhanced erythroid proliferation and/or survival, but did not affect differentiation. These findings identify CD163 on macrophages as an adhesion receptor for erythroblasts in erythroblastic islands, and suggest a regulatory role for CD163 during erythropoiesis. PMID- 17353346 TI - Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene. AB - Malignancies arising from retrovirally transduced hematopoietic stem cells have been reported in animal models and human gene therapy trials. Whether mature lymphocytes are susceptible to insertional mutagenesis is unknown. We have characterized a primary human CD8(+) T-cell clone, which exhibited logarithmic ex vivo growth in the absence of exogenous cytokine support for more than 1 year after transduction with a murine leukemia virus-based vector encoding the T-cell growth factor IL-15. Phenotypically, the clone was CD28(-), CD45RA(-), CD45RO(+), and CD62L(-), a profile consistent with effector memory T lymphocytes. After gene transfer with tumor-antigen-specific T-cell receptors, the clone secreted IFN gamma upon encountering tumor targets, providing further evidence that they derived from mature lymphocytes. Gene-expression analyses revealed no evidence of insertional activation of genes flanking the retroviral insertion sites. The clone exhibited constitutive telomerase activity, and the presence of autocrine loop was suggested by impaired cell proliferation following knockdown of IL-15R alpha expression. The generation of this cell line suggests that nonphysiologic expression of IL-15 can result in the long-term in vitro growth of mature human T lymphocytes. The cytokine-independent growth of this line was a rare event that has not been observed in other IL-15 vector transduction experiments or with any other integrating vector system. It does not appear that the retroviral vector integration sites played a role in the continuous growth of this cell clone, but this remains under investigation. PMID- 17353347 TI - Stereoselective metabolism of prasugrel in humans using a novel chiral liquid chromatography-tandem mass spectrometry method. AB - A liquid chromatography-tandem mass spectrometry method was developed to chromatographically separate the four stereoisomers of the active metabolite of prasugrel, R-138727, in human plasma after derivatization with bromomethoxyacetophenone to stabilize the molecule. This technique was designed to determine the relative contribution of each stereoisomer, based on statistical analyses of each stereoisomer's chromatographic peak areas. The methodology was validated and used for the analysis of clinical samples in which R-138727 had been derivatized at the time of blood collection. This technique can be useful to determine the ratios of stereoisomers in biological samples (e.g., plasma) especially in situations in which authentic standards of each individual stereoisomer are scarce or unavailable. In humans, the metabolic formation of R 138727 from prasugrel was found to be stereoselective, where 84% of R-138727 was present as RS and RR, the two most pharmacologically potent isomers, whereas the SR and SS enantiomers accounted for approximately 16%. The ratios of the R-138727 stereoisomers were consistent among subjects, regardless of the dose or time of sample collection or whether the blood was sampled after the first dose or after 4 weeks of therapy. PMID- 17353348 TI - Induction of drug-metabolizing enzymes by garlic and allyl sulfide compounds via activation of constitutive androstane receptor and nuclear factor E2-related factor 2. AB - Garlic oil (GO) contains several linear sulfur compounds, including diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), that induce drug-metabolizing enzymes such as CYP2B and NAD(P)H quinone oxidoreductase 1 (NQO1). CYP2B and NQO1 are primarily regulated by constitutive androstane receptor (CAR) and nuclear factor E2-related factor 2 (Nrf2) transcription factors, respectively. The purpose of this study was to determine whether GO and its specific constituents induce these two enzymes via CAR and Nrf2 activation. Female Wistar-Kyoto (WKY) rats express little CAR protein and exhibit less induction of CYP2B1/2 than males. GO, DAS, and DADS, but not DATS, induced CYP2B1/2 mRNA levels to a greater extent in WKY males than in females, suggesting CAR activation. Conversely, DAS induced NQO1 levels equally in WKY males and females, indicating CAR-independent induction in rats. DAS, but not GO, DADS, or DATS, induced CYP2B10 mRNA levels 530-fold in wild-type (WT) mice, whereas this induction was attenuated in CAR(-/-) mice. DAS induced NQO1 in WT and CAR(-/-) mice equally, suggesting CAR-independent induction in mice. DAS induced NQO1 5 fold in WT mice, whereas induction was completely absent in Nrf2(-/-) mice, indicating DAS also activates Nrf2. DAS induction of CYP2B10 mRNA was independent of Nrf2 presence or absence. In in vivo transcription assays, DAS activated the human CYP2B6 promoter, and the antioxidant response element of the human NQO1 promoter, respectively. These studies indicate that GO constituents, particularly DAS, activate CAR and Nrf2 to induce drug-metabolizing enzymes. PMID- 17353349 TI - Metabolism of prazosin in rat, dog, and human liver microsomes and cryopreserved rat and human hepatocytes and characterization of metabolites by liquid chromatography/tandem mass spectrometry. AB - Prazosin (2-[4-(2-furanoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline) is an antihypertensive agent that was introduced to the market in 1976. It has since established an excellent safety record. However, in vitro metabolism of prazosin has not been investigated. This study describes the in vitro biotransformation of prazosin in liver microsomes from rats, dogs, and humans, as well as rat and human cryopreserved hepatocytes and characterization of metabolites using liquid chromatography/tandem mass spectrometry. The major in vivo biotransformation pathways reported previously in rats and dogs include demethylation, amide hydrolysis, and O-glucuronidation. These metabolic pathways were also confirmed in our study. In addition, several new metabolites were characterized, including a stable carbinolamine, an iminium species, and an enamine-all formed via oxidation of the piperazine ring. Two ring-opened metabolites generated following oxidative cleavage of the furan ring were also identified. Using semicarbazide hydrochloride as a trapping agent, an intermediate arising from opening of the furan ring was captured as a pyridazine product. In the presence of glutathione, three glutathione conjugates were detected in microsomal incubations, although they were not detected in cryopreserved hepatocytes. These data support ring opening of the furan via a reactive gamma-keto-alpha,beta-unsaturated aldehyde intermediate. In the presence of UDP-glucuronic acid, prazosin underwent conjugation to form an N-glucuronide not reported previously. Our in vitro investigations have revealed additional metabolic transformations of prazosin and have shown the potential of prazosin to undergo bioactivation through metabolism of the furan ring to a reactive intermediate. PMID- 17353350 TI - Regional expression and activity of breast cancer resistance protein (Bcrp/Abcg2) in mouse intestine: overlapping distribution with sulfotransferases. AB - Breast cancer resistance protein (Bcrp/Abcg2) is a member of the ATP-binding cassette transporter family with the ability to transport a variety of sulfate conjugates. In the present study, the regional expression and activity of Bcrp and sulfotransferases (SULTs/Sults) were investigated in mouse intestine. Western blotting analysis revealed the highest expression of Bcrp in the ileum over the duodenum, jejunum, and colon. Functional analysis of Bcrp was performed in everted intestinal sacs using 4-methylumbelliferone (4MU). The mucosal secretion clearance of 4MU sulfate formed in the enterocytes was markedly reduced in the jejunum, ileum, and colon of Bcrp (-/-) mice in comparison with wild-type mice, whereas a slight and nonsignificant reduction was observed in the duodenum. The reduction in the mucosal secretion clearance was most marked in the ileum followed by the colon and jejunum. In addition, the mucosal secretion clearance of minoxidil sulfate, an active metabolite of minoxidil, was also significantly reduced in the intestine of Bcrp (-/-) mice. The sulfation activity of 4MU was higher in the colon than in the small intestine where glucuronidation activity was somewhat higher than the sulfation activity. Real-time polymerase chain reaction analysis showed that the expression of sulfotransferases, such as Sult1a1/2, Sult1b1, and Sult1d1, was also highest in the colon. These results suggest that Bcrp activity is higher in the mid to lower intestine and that the cooperation of Bcrp and SULT provides an important detoxification pathway, particularly in the colon. PMID- 17353351 TI - G551D and G1349D, two CF-associated mutations in the signature sequences of CFTR, exhibit distinct gating defects. AB - Mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR) result in cystic fibrosis (CF). CFTR is a chloride channel that is regulated by phosphorylation and gated by ATP binding and hydrolysis at its nucleotide binding domains (NBDs). G551D-CFTR, the third most common CF associated mutation, has been characterized as having a lower open probability (Po) than wild-type (WT) channels. Patients carrying the G551D mutation present a severe clinical phenotype. On the other hand, G1349D, also a mutant with gating dysfunction, is associated with a milder clinical phenotype. Residues G551 and G1349 are located at equivalent positions in the highly conserved signature sequence of each NBD. The physiological importance of these residues lies in the fact that the signature sequence of one NBD and the Walker A and B motifs from the other NBD form the ATP-binding pocket (ABP1 and ABP2, named after the location of the Walker A motif) once the two NBDs dimerize. Our studies show distinct gating characteristics for these mutants. The G551D mutation completely eliminates the ability of ATP to increase the channel activity, and the observed activity is approximately 100-fold smaller than WT-CFTR. G551D-CFTR does not respond to ADP, AMP-PNP, or changes in [Mg(2+)]. The low activity of G551D-CFTR likely represents the rare ATP-independent gating events seen with WT channels long after the removal of ATP. G1349D-CFTR maintains ATP dependence, albeit with a Po approximately 10-fold lower than WT. Interestingly, compared to WT results, the ATP dose-response relationship of G1349D-CFTR is less steep and shows a higher apparent affinity for ATP. G1349D data could be well described by a gating model that predicts that binding of ATP at ABP1 hinders channel opening. Thus, our data provide a quantitative explanation at the single-channel level for different phenotypes presented by patients carrying these two mutations. In addition, these results support the idea that CFTR's two ABPs play distinct functional roles in gating. PMID- 17353352 TI - Structural determinants of the closed KCa3.1 channel pore in relation to channel gating: results from a substituted cysteine accessibility analysis. AB - In this work we address the question of the KCa3.1 channel pore structure in the closed configuration in relation to the contribution of the C-terminal end of the S6 segments to the Ca(2+)-dependent gating process. Our results based on SCAM (substituted cysteine accessibility method) experiments first demonstrate that the S6 transmembrane segment of the open KCa3.1 channel contains two distinct functional domains delimited by V282 with MTSEA and MTSET binding leading to a total channel inhibition at positions V275, T278, and V282 and to a steep channel activation at positions A283 and A286. The rates of modification by MTSEA (diameter 4.6 A) of the 275C (central cavity) and 286C residues (S6 C-terminal end) for the closed channel configuration were found to differ by less than sevenfold, whereas experiments performed with the larger MTSET reagent (diameter 5.8 A) resulted in modification rates 10(3)-10(4) faster for cysteines at 286 compared with 275. Consistent with these results, the modification rates of the cavity lining 275C residue by MTSEA, Et-Hg(+), and Ag(+) appeared poorly state dependent, whereas modification rates by MTSET were 10(3) faster for the open than the closed configuration. A SCAM analysis of the channel inner vestibule in the closed state revealed in addition that cysteine residues at 286 were accessible to MTS reagents as large as MTS-PtrEA, a result supported by the observation that binding of MTSET to cysteines at positions 283 or 286 could neither sterically nor electrostatically block the access of MTSEA to the closed channel cavity (275C). It follows that the closed KCa3.1 structure can hardly be accountable by an inverted teepee-like structure as described for KcsA, but is better represented by a narrow passage centered at V282 (equivalent to V474 in Shaker) connecting the channel central cavity to the cytosolic medium. This passage would not be however restrictive to the diffusion of small reagents such as MTSEA, Et-Hg(+), and Ag(+), arguing against the C-terminal end of S6 forming an obstructive barrier to the diffusion of K(+) ions for the closed channel configuration. PMID- 17353353 TI - A U-turn motif-containing stem-loop in the coronavirus 5' untranslated region plays a functional role in replication. AB - The 5' untranslated region (UTR) of the mouse hepatitis virus (MHV) genome contains cis-acting sequences necessary for transcription and replication. A consensus secondary structural model of the 5' 140 nucleotides of the 5' UTRs of nine coronaviruses (CoVs) derived from all three major CoV groups is presented and characterized by three major stem-loops, SL1, SL2, and SL4. NMR spectroscopy provides structural support for SL1 and SL2 in three group 2 CoVs, including MHV, BCoV, and HCoV-OC43. SL2 is conserved in all CoVs, typically containing a pentaloop (C47-U48-U49-G50-U51 in MHV) stacked on a 5 base-pair stem, with some sequences containing an additional U 3' to U51; SL2 therefore possesses sequence features consistent with a U-turn-like conformation. The imino protons of U48 in the wild-type RNA, and G48 in the U48G SL2 mutant RNA, are significantly protected from exchange with solvent, consistent with a hydrogen bonding interaction critical to the hairpin loop architecture. SL2 is required for MHV replication; MHV genomes containing point substitutions predicted to perturb the SL2 structure (U48C, U48A) were not viable, while those that maintain the structure (U48G and U49A) were viable. The U48C MHV mutant supports both positive and negative-sense genome-sized RNA synthesis, but fails to direct the synthesis of positive- or negative-sense subgenomic RNAs. These data support the existence of the SL2 in our models, and further suggest a critical role in coronavirus replication. PMID- 17353354 TI - Identification and functional analysis of a novel human CYP2E1 far upstream enhancer. AB - Both transcriptional and post-transcriptional CYP2E1 regulatory mechanisms are known, resulting in 20-fold or greater variation in CYP2E1 expression. To evaluate functional regulatory elements controlling transcription, CYP2E1 promoter constructs were used to make adenovirus vectors containing CYP2E1 promoter-driven luciferase reporters for analyses in both primary human hepatocytes and HepG2 cells. A 1.2-kilobase pair portion of the CYP2E1 promoter was associated with 5- to 10-fold greater luciferase activity. This upstream region contained five direct repeats of 59 base pairs (bp) that increased thymidine kinase-driven luciferase reporter activity in HepG2 cells more than 5 fold, regardless of orientation. Electrophoretic mobility shift assays (EMSAs) identified sequence-specific nuclear protein binding to the 59-bp repeats that was dependent on a 17-bp sequence containing a canonical GATA binding site (WGATAR). Competitive and supershift EMSA identified the participation of GATA4, another GATA family member or GATA-like factor, and a third factor unrelated to the GATA family. Involvement of the tricho-rhino-phalangeal syndrome-1 factor, which also binds a GATA sequence, was eliminated. Rather, competitive EMSA using known binding sequences for the orphan nuclear receptors, steroidogenic factor-1 (or NR5A1), and fetoprotein transcription factor (or NR5A2) implicated an NR5A member in binding a sequence overlapping the canonical GATA. Chromatin immunoprecipitation assay demonstrated in vivo binding of NR5A2 to the enhancer sequence in human hepatocytes. The enhancer sequence is conserved within the human population but seems species-specific. The identification of this novel enhancer and its putative mechanism adds to the complexities of human CYP2E1 regulation. PMID- 17353355 TI - Chromosome breakage after G2 checkpoint release. AB - DNA double-strand break (DSB) repair and checkpoint control represent distinct mechanisms to reduce chromosomal instability. Ataxia telangiectasia (A-T) cells have checkpoint arrest and DSB repair defects. We examine the efficiency and interplay of ATM's G2 checkpoint and repair functions. Artemis cells manifest a repair defect identical and epistatic to A-T but show proficient checkpoint responses. Only a few G2 cells enter mitosis within 4 h after irradiation with 1 Gy but manifest multiple chromosome breaks. Most checkpoint-proficient cells arrest at the G2/M checkpoint, with the length of arrest being dependent on the repair capacity. Strikingly, cells released from checkpoint arrest display one to two chromosome breaks. This represents a major contribution to chromosome breakage. The presence of chromosome breaks in cells released from checkpoint arrest suggests that release occurs before the completion of DSB repair. Strikingly, we show that checkpoint release occurs at a point when approximately three to four premature chromosome condensation breaks and approximately 20 gammaH2AX foci remain. PMID- 17353356 TI - Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization. AB - The molecular mechanisms of how primordial adherens junctions (AJs) evolve into spatially separated belt-like AJs and tight junctions (TJs) during epithelial polarization are not well understood. Previously, we reported the establishment of ZO-1/ZO-2-deficient cultured epithelial cells (1[ko]/2[kd] cells), which lacked TJs completely. In the present study, we found that the formation of belt like AJs was significantly delayed in 1(ko)/2(kd) cells during epithelial polarization. The activation of Rac1 upon primordial AJ formation is severely impaired in 1(ko)/2(kd) cells. Our data indicate that ZO-1 plays crucial roles not only in TJ formation, but also in the conversion from "fibroblastic" AJs to belt-like "polarized epithelial" AJs through Rac1 activation. Furthermore, to examine whether ZO-1 itself mediate belt-like AJ and TJ formation, respectively, we performed a mutational analysis of ZO-1. The requirement for ZO-1 differs between belt-like AJ and TJ formation. We propose that ZO-1 is directly involved in the establishment of two distinct junctional domains, belt-like AJs and TJs, during epithelial polarization. PMID- 17353357 TI - Absence of integrin-mediated TGFbeta1 activation in vivo recapitulates the phenotype of TGFbeta1-null mice. AB - The multifunctional cytokine transforming growth factor (TGF) beta1 is secreted in a latent complex with its processed propeptide (latency-associated peptide [LAP]). TGFbeta1 must be functionally released from this complex before it can engage TGFbeta receptors. One mechanism of latent TGFbeta1 activation involves interaction of the integrins alpha v beta6 and alpha v beta8 with an RGD sequence in LAP; other putative latent TGFbeta1 activators include thrombospondin-1, oxidants, and various proteases. To assess the contribution of RGD-binding integrins to TGFbeta1 activation in vivo, we created a mutation in Tgfb1 encoding a nonfunctional variant of the RGD sequence (RGE). Mice with this mutation (Tgfb1(RGE/RGE)) display the major features of Tgfb1(-/-) mice (vasculogenesis defects, multiorgan inflammation, and lack of Langerhans cells) despite production of normal levels of latent TGFbeta1. These findings indicate that RGD binding integrins are requisite latent TGFbeta1 activators during development and in the immune system. PMID- 17353358 TI - Critical requirement for cell cycle inhibitors in sustaining nonproliferative states. AB - In adult vertebrates, most cells are not in the cell cycle at any one time. Physiological nonproliferation states encompass reversible quiescence and permanent postmitotic conditions such as terminal differentiation and replicative senescence. Although these states appear to be attained and maintained quite differently, they might share a core proliferation-restricting mechanism. Unexpectedly, we found that all sorts of nonproliferating cells can be mitotically reactivated by the sole suppression of histotype-specific cyclin dependent kinase (cdk) inhibitors (CKIs) in the absence of exogenous mitogens. RNA interference-mediated suppression of appropriate CKIs efficiently triggered DNA synthesis and mitosis in established and primary terminally differentiated skeletal muscle cells (myotubes), quiescent human fibroblasts, and senescent human embryo kidney cells. In serum-starved fibroblasts and myotubes alike, cell cycle reactivation was critically mediated by the derepression of cyclin D-cdk4/6 complexes. Thus, both temporary and permanent growth arrest must be actively maintained by the constant expression of CKIs, whereas the cell cycle-driving cyclins are always present or can be readily elicited. In principle, our findings could find wide application in biotechnology and tissue repair whenever cell proliferation is limiting. PMID- 17353359 TI - A CDK-related kinase regulates the length and assembly of flagella in Chlamydomonas. AB - Little is known about how cells regulate the size of their organelles. In this study, we find that proper flagellar length control in Chlamydomonas reinhardtii requires the activity of a new member of the cyclin-dependent kinase (CDK) family, which is encoded by the LF2 (long flagella 2) gene. This novel CDK contains all of the important residues that are essential for kinase activity but lacks the cyclin-binding motif PSTAIRE. Analysis of genetic lesions in a series of lf2 mutant alleles and site-directed mutagenesis of LF2p reveals that improper flagellar length and defective flagellar assembly correlate with the extent of disruption of conserved kinase structures or residues by mutations. LF2p appears to interact with both LF1p and LF3p in the cytoplasm, as indicated by immunofluorescence localization, sucrose density gradients, cell fractionation, and yeast two-hybrid experiments. We propose that LF2p is the catalytic subunit of a regulatory kinase complex that controls flagellar length and flagellar assembly. PMID- 17353361 TI - Identification of prothymosin-alpha1, the necrosis-apoptosis switch molecule in cortical neuronal cultures. AB - We initially identified a nuclear protein, prothymosin-alpha1 (ProTalpha), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProTalpha inhibited necrosis of cultured neurons by preventing rapid loss of cellular adenosine triphosphate levels by reversing the decreased membrane localization of glucose transporters but caused apoptosis through up-regulation of proapoptotic Bcl(2) family proteins. The apoptosis caused by ProTalpha was further inhibited by growth factors, including brain-derived neurotrophic factor. The ProTalpha induced cell death mode switch from necrosis to apoptosis was also reproduced in experimental ischemia-reperfusion culture experiments, although the apoptosis level was markedly reduced, possibly because of the presence of growth factors in the reperfused serum. Knock down of PKCbeta(II) expression prevented this cell death mode switch. Collectively, these results suggest that ProTalpha is an extracellular signal protein that acts as a cell death mode switch and could be a promising candidate for preventing brain strokes with the help of known apoptosis inhibitors. PMID- 17353360 TI - A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle. AB - Mutations in human survival motor neurons 1 (SMN1) cause spinal muscular atrophy (SMA) and are associated with defects in assembly of small nuclear ribonucleoproteins (snRNPs) in vitro. However, the etiological link between snRNPs and SMA is unclear. We have developed a Drosophila melanogaster system to model SMA in vivo. Larval-lethal Smn-null mutations show no detectable snRNP reduction, making it unlikely that these animals die from global snRNP deprivation. Hypomorphic mutations in Smn reduce dSMN protein levels in the adult thorax, causing flightlessness and acute muscular atrophy. Mutant flight muscle motoneurons display pronounced axon routing and arborization defects. Moreover, Smn mutant myofibers fail to form thin filaments and phenocopy null mutations in Act88F, which is the flight muscle-specific actin isoform. In wild-type muscles, dSMN colocalizes with sarcomeric actin and forms a complex with alpha-actinin, the thin filament crosslinker. The sarcomeric localization of Smn is conserved in mouse myofibrils. These observations suggest a muscle-specific function for SMN and underline the importance of this tissue in modulating SMA severity. PMID- 17353362 TI - The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization. AB - Cell polarization is required for virtually all functions of T cells, including transendothelial migration in response to chemokines. However, the molecular pathways that establish T cell polarity are poorly understood. We show that the activation of the partitioning defective (Par) polarity complex is a key event during Rap1- and chemokine-induced T cell polarization. Intracellular localization and activation of the Par complex are initiated by Rap1 and require Cdc42 activity. The Rac activator Tiam1 associates with both Rap1 and components of the Par complex, and thereby may function to connect the Par polarity complex to Rap1 and to regulate the Rac-mediated actin remodelling required for T cell polarization. Consistent with these findings, Tiam1-deficient T cells are impaired in Rap1- and chemokine-induced polarization and chemotaxis. Our studies implicate Tiam1 and the Par polarity complex in polarization of T cells, and provide a mechanism by which chemokines and Rap1 regulate T cell polarization and chemotaxis. PMID- 17353363 TI - Syk, c-Src, the alphavbeta3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption. AB - In this study, we establish that the tyrosine kinase Syk is essential for osteoclast function in vitro and in vivo. Syk(-/-) osteoclasts fail to organize their cytoskeleton, and, as such, their bone-resorptive capacity is arrested. This defect results in increased skeletal mass in Syk(-/-) embryos and dampened basal and stimulated bone resorption in chimeric mice whose osteoclasts lack the kinase. The skeletal impact of Syk deficiency reflects diminished activity of the mature osteoclast and not impaired differentiation. Syk regulates bone resorption by its inclusion with the alpha v beta3 integrin and c-Src in a signaling complex, which is generated only when alpha v beta3 is activated. Upon integrin occupancy, c-Src phosphorylates Syk. Alpha v beta3-induced phosphorylation of Syk and the latter's capacity to associate with c-Src is mediated by the immunoreceptor tyrosine-based activation motif (ITAM) proteins Dap12 and FcRgamma. Thus, in conjunction with ITAM-bearing proteins, Syk, c-Src, and alpha v beta3 represent an essential signaling complex in the bone-resorbing osteoclast, and, therefore, each is a candidate therapeutic target. PMID- 17353364 TI - Smad4 is critical for self-renewal of hematopoietic stem cells. AB - Members of the transforming growth factor beta (TGF-beta) superfamily of growth factors have been shown to regulate the in vitro proliferation and maintenance of hematopoietic stem cells (HSCs). Working at a common level of convergence for all TGF-beta superfamily signals, Smad4 is key in orchestrating these effects. The role of Smad4 in HSC function has remained elusive because of the early embryonic lethality of the conventional knockout. We clarify its role by using an inducible model of Smad4 deletion coupled with transplantation experiments. Remarkably, systemic induction of Smad4 deletion through activation of MxCre was incompatible with survival 4 wk after induction because of anemia and histopathological changes in the colonic mucosa. Isolation of Smad4 deletion to the hematopoietic system via several transplantation approaches demonstrated a role for Smad4 in the maintenance of HSC self-renewal and reconstituting capacity, leaving homing potential, viability, and differentiation intact. Furthermore, the observed down regulation of notch1 and c-myc in Smad4(-/-) primitive cells places Smad4 within a network of genes involved in the regulation HSC renewal. PMID- 17353365 TI - Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. AB - Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-alpha, and natural killer (NK) cell expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death-inducing receptor. IFN-alpha concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-alpha/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen specific mechanism can be switched on by cytokines produced during active HBV infection. PMID- 17353366 TI - IL-31-IL-31R interactions negatively regulate type 2 inflammation in the lung. AB - Interleukin (IL) 31Ralpha (glycoprotein 130-like monocyte receptor and glycoprotein 130-like receptor) heterodimerizes with oncostatin M receptor beta to bind IL-31, a cytokine expressed preferentially by CD4(+) T helper type 2 (Th2) cells. However, the functions of IL-31-IL-31R signaling in immune regulation remain unknown. Here, we identify a novel role for IL-31R in limiting type 2 inflammation in the lung. After intravenous injection of Schistosoma mansoni eggs, IL-31Ralpha(-/-) mice developed severe pulmonary inflammation, characterized by an increase in the area of granulomatous inflammation, increased numbers of resistin-like molecule alpha(+) cells, and enhanced collagen deposition compared to WT counterparts. In vitro, macrophages generated from IL 31Ralpha(-/-) mice promoted enhanced ovalbumin-specific CD4(+) T cell proliferation and purified naive CD4(+) T cells from IL-31Ralpha(-/-) mice exhibited enhanced proliferation and expression of Th2 cytokines, identifying a T cell- and macrophage-intrinsic regulatory function for IL-31R signaling. In contrast, the generation of CD4(+) T cell-mediated Th1 responses were normal in IL-31Ralpha(-/-) mice, suggesting that the regulatory role of IL-31R signaling is limited to type 2 responses. Together, these data implicate IL-31R signaling as a novel negative regulatory pathway that specifically limits type 2 inflammation. PMID- 17353367 TI - Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma. AB - To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor samples of the activated B cell-like (ABC), germinal center B cell-like (GCB), and primary mediastinal B cell lymphoma (PMBL) subgroups of DLBCL. The frequency of legitimate CSR was lower in ABC DLBCL than in GCB DLBCL and PMBL. In contrast, ABC DLBCL had a higher frequency of internal deletions within the switch mu (Smu) region compared with GCB DLBCL and PMBL. ABC DLBCLs also had frequent deletions within Sgamma and other illegitimate switch recombinations. Sequence analysis revealed ongoing Smu deletions within ABC DLBCL tumor clones, which were accompanied by ongoing duplications and activation-induced cytidine deaminase dependent somatic mutations. Unexpectedly, short fragments derived from multiple chromosomes were interspersed within Smu in one case. These findings suggest that ABC DLBCLs have abnormalities in the regulation of CSR that could predispose to chromosomal translocations. Accordingly, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving BCL6, MYC, and a novel translocation partner, SPIB. PMID- 17353368 TI - A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76. AB - The SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is a pivotal element of the signaling machinery controlling T cell receptor (TCR)-mediated activation. Here, we identify 14-3-3epsilon and zeta proteins as SLP-76 binding partners. This interaction was induced by TCR ligation and required phosphorylation of SLP-76 at serine 376. Ribonucleic acid interference and in vitro phosphorylation experiments showed that serine 376 is the target of the hematopoietic progenitor kinase 1 (HPK-1). Interestingly, either S376A mutation or HPK-1 knockdown resulted in increased TCR-induced tyrosine phosphorylation of SLP-76 and phospholipase C-gamma1. Moreover, an SLP-76-S376A mutant induced higher interleukin 2 gene transcription than wild-type SLP-76. These data reveal a novel negative feedback loop involving HPK-1-dependent serine phosphorylation of SLP-76 and 14-3-3 protein recruitment, which tunes T cell activation. PMID- 17353369 TI - Oncogenic signaling: new insights and controversies from chronic myeloid leukemia. AB - Chronic myeloid leukemia (CML), which is caused by the BCR-ABL fusion tyrosine kinase, is one of the most intensively studied human cancers. ABL kinase inhibitors have been spectacularly successful in treating CML, but disease persistence and acquired drug resistance can prevent eradication and cure of the leukemia. The development of better therapies will depend on a full understanding of signaling pathways in CML, facilitated by model studies using mutant mice. PMID- 17353370 TI - Lack of Foxp3 function and expression in the thymic epithelium. AB - Foxp3 is essential for the commitment of differentiating thymocytes to the regulatory CD4(+) T (T reg) cell lineage. In humans and mice with a genetic Foxp3 deficiency, absence of this critical T reg cell population was suggested to be responsible for the severe autoimmune lesions. Recently, it has been proposed that in addition to T reg cells, Foxp3 is also expressed in thymic epithelial cells where it is involved in regulation of early thymocyte differentiation and is required to prevent autoimmunity. Here, we used genetic tools to demonstrate that the thymic epithelium does not express Foxp3. Furthermore, we formally showed that genetic abatement of Foxp3 in the hematopoietic compartment, i.e. in T cells, is both necessary and sufficient to induce the autoimmune lesions associated with Foxp3 loss. In contrast, deletion of a conditional Foxp3 allele in thymic epithelial cells did not result in detectable changes in thymocyte differentiation or pathology. Therefore, in mice the only known role for Foxp3 remains promotion of T reg cell differentiation within the T cell lineage, whereas there is no role for Foxp3 in thymic epithelial cells. PMID- 17353371 TI - Genotype and protein expression after bone marrow transplantation for adrenoleukodystrophy. AB - BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder. It is caused by impaired function of ALD protein that results in accumulation of very long-chain fatty acids in tissues and body fluids. So far, hematopoietic stem cell transplantation (HSCT) constitutes the only curative approach able to prevent the progression of cerebral X-ALD. However, biological mechanisms of this beneficial approach are still unknown. OBJECTIVE: To describe the effect of HSCT in a family with various X-ALD disease forms by ALD mutation and protein expression analysis. DESIGN, SETTING, AND PATIENTS: In a family with various X-ALD forms, an ALD mutation screening was performed. Two boys had cerebral X-ALD and underwent HSCT. One of them is alive and well without any further neurological deterioration, whereas his cousin died of transplantation-related complications at day 76. The postmortem specimens were analyzed by genotyping and immunohistochemical assays. RESULTS: All of the affected family members carry an as-yet-undescribed large ALD gene deletion (NC_000023:g.152512130-152520645del) resulting in a complete lack of ALD protein expression on immunofluorescence analysis. After engraftment, both patients who underwent HSCT showed complete chimerism in blood. Postmortem studies in 1 patient revealed both mutant and wild-type ALD sequences in each of 23 analyzed tissues, indicating mixed chimerism. Furthermore, immunohistochemical staining for ALD protein revealed no differences between patient and control tissues including blood cells, bone marrow, and glial cells as well as neurons. CONCLUSION: To our knowledge, our analysis provides the first evidence for the stable development of a wild-type X-ALD genotype and peroxisomal ALD protein expression in a great variety of human tissues following HSCT. PMID- 17353372 TI - Pittsburgh compound B retention and verification of amyloid deposition. PMID- 17353373 TI - Effects of methylphenidate on response to oral levodopa: a double-blind clinical trial. AB - OBJECTIVE: To determine if repeated dosing with methylphenidate hydrochloride (MPD) (Ritalin; Novartis Pharmaceuticals, East Hanover, NJ), an inhibitor of the dopamine transporter, would augment the effects of oral levodopa in patients with Parkinson disease. DESIGN: The study was a double-blind, randomized, placebo controlled crossover trial. SETTING: The trial was conducted at the General Clinical Research Center (GCRC) as an inpatient study. Subjects Thirteen people with idiopathic Parkinson disease and a fluctuating motor response to levodopa were recruited from movement disorder clinics as a convenience sample. One subject was excluded because he did not have a 10% increase in tapping speed in response to levodopa. The remaining 12 subjects completed the protocol. INTERVENTIONS: A 0.4-mg/kg dose of MPD was administered orally at 8 am, noon, and 4 pm in conjunction with the subjects' normal oral antiparkinsonian medications. Oral levodopa dosage was decreased as clinically feasible during the first 4 days in the GCRC during open-label administration of MPD and hourly monitoring of parkinsonism and vital signs between 7 am and 8 pm. Subjects were discharged taking their usual antiparkinsonian medications without MPD. They returned 1 and 2 weeks later to the GCRC for 1 day of hourly monitoring of their response to the medication regimen derived during the 4 days in the GCRC, once with MPD and once with identical-appearing placebo, in a randomized sequence and double-blind conditions. MAIN OUTCOME MEASURES: The main outcome measure was the duration of "on" time between 9 am and 8 pm measured by an increase in tapping speed by 10% over the average of the 7 am to 8 am predosing tapping speed measurements. Secondary measures were estimates of "on" time obtained with the timed walking task, tremor scores, and dyskinesia scores. In addition, averages of hourly tapping speeds, walking speed, tremor scores, dyskinesia scores, vital signs, and analog scale scores for mood, anxiety, and fatigue between 9 am and 8 pm were examined. Adverse events on the double-blinded days were compared. RESULTS: Methylphenidate tended to increase the time "on" as measured by tapping (P = .09) but not by walking time or dyskinesia scores (P = .40 and .42, respectively). Methylphenidate tended to increase average tapping speed, decrease time to perform walking task, decrease tremor, and increase dyskinesia score but only the decrease in tremor reached significance. Neither the investigators nor the subjects could reliably identify active drug. Methylphenidate was well tolerated. CONCLUSIONS: The effects of 0.4 mg/kg of MPD 3 times per day on the motor response to levodopa were small and variable and judged to be clinically insignificant. Trial Registration clinicaltrials.gov Identifier: NCT00359723. PMID- 17353374 TI - New ideas in epilepsy genetics: novel epilepsy genes, copy number alterations, and gene regulation. AB - The majority of genes associated with epilepsy syndromes to date are ion channel genes. Selection bias may have allowed us to establish their role in epilepsy based on a priori knowledge of the significance of these proteins in regulating neuronal excitability. There are, however, more than 3000 genes expressed at the synapse, as well as many other genes expressed nearby in supporting cells and glia that can likewise regulate excitability. Identification of new genes involved in epilepsy may arise from studying the targets of anticonvulsant medications, ascertainment of an epileptic phenotype in mice, or as a result of positional cloning efforts. There are several loci for idiopathic focal and generalized epilepsies that lie in chromosomal regions that are devoid of known ion channels; therefore, the number of novel genes involved in epilepsy is likely to increase. Establishing the role of these novel genes in the pathogenesis of epilepsy has not been an easy task compared with the relative ease with which ion channel mutations can be studied. This review will describe several novel epilepsy genes and will then discuss other genetic causes of epilepsy, including alterations of chromosomal copy number and gene regulatory elements. PMID- 17353375 TI - Establishing subtypes of the continuum of frontal lobe impairment in amyotrophic lateral sclerosis. AB - This review summarizes recent advances in our understanding of the cognitive changes seen in patients with amyotrophic lateral sclerosis (ALS). Emphasis is placed on identifying and diagnosing subtypes of ALS patients with a continuum of frontotemporal impairment. The reviewed literature focuses on progress made in the past 20 years, with an emphasis on studies measuring abnormalities in ALS patients without dementia. We describe peer-reviewed journal articles using neuropsychological batteries and imaging techniques. We also discuss debates raised in recent meetings. In the past 2 decades, the field of ALS has been transformed in terms of its understanding of extramotor cerebral changes. Particularly in the past 10 years, investigators have invalidated the theory that cognitive abnormality in ALS patients is simply a rarely occurring, frank frontotemporal lobar degeneration syndrome. Instead, a growing body of evidence suggests that ALS patients with comorbid frontotemporal lobar degeneration lie on a spectrum of frontotemporal abnormality, with a large proportion of ALS patients possessing a range of behavioral and cognitive changes. As more investigations use standardized tools measuring behavior and cognition, distinct subtypes may be diagnosed. PMID- 17353376 TI - Interpreting the randomized clinical trial of constraint-induced movement therapy. PMID- 17353377 TI - Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. AB - BACKGROUND: To develop preventive therapy for Alzheimer disease (AD), it is essential to develop AD-related biomarkers that identify at-risk individuals in the same way that cholesterol levels identify persons at risk for heart disease. OBJECTIVE: To determine whether plasma levels of amyloid beta protein (Abeta40 and Abeta42) are useful for identifying cognitively normal elderly white subjects at increased risk for mild cognitive impairment (MCI) and AD. DESIGN: Using well established sandwich enzyme-linked immunosorbent assays, plasma Abeta40 and Abeta42 levels were analyzed at baseline in a prospective, elderly white cohort followed up for 2 to 12 (median, 3.7) years to detect incident cases of MCI or AD. SETTING: Cognitively normal, community-based white volunteers recruited from primary care settings into the Mayo Rochester Alzheimer Disease Patient Registry. Patients We followed up 563 cognitively normal white volunteers (median age, 78 years; 62% female) who had at least 1 follow-up visit after measurement of baseline plasma Abeta levels. MAIN OUTCOME MEASURES: The primary outcome was time to development of MCI or AD. The secondary outcome was the annualized rate of cognitive change in patients for whom we had 2 Mattis Dementia Rating Scale evaluations 3 to 7 years apart. RESULTS: During follow-up, 53 subjects developed MCI or AD. Subjects with plasma Abeta42/Abeta40 ratios in the lower quartiles showed significantly greater risk of MCI or AD (P = .04, adjusted for age and apolipoprotein E genotype). Comparison of subjects with plasma Abeta42/Abeta40 ratios in the lowest vs the highest quartile gave a relative risk of 3.1 (95% confidence interval, 1.1-8.3). After adjusting for age and apolipoprotein E genotype, regression analysis using annualized changes in the Dementia Rating Scale scores as an outcome variable showed that participants with lower Abeta42/Abeta40 ratios had greater cognitive decline (P = .02). CONCLUSION: The plasma Abeta42/Abeta40 ratio may be a useful premorbid biomarker for identifying cognitively normal elderly white subjects who are at increased risk for developing MCI or AD. PMID- 17353378 TI - Novel panel of cerebrospinal fluid biomarkers for the prediction of progression to Alzheimer dementia in patients with mild cognitive impairment. AB - OBJECTIVE: To use proteomic analysis of cerebrospinal fluid to discover novel proteins and peptides able to differentiate between patients with stable mild cognitive impairment (MCI) and those who will progress to Alzheimer disease (AD). DESIGN: Baseline cerebrospinal fluid samples from patients with MCI and healthy controls were profiled using surface-enhanced laser desorption/ionization time-of flight mass spectrometry. SETTING: Memory disorder clinic. PARTICIPANTS: Patients with MCI (n = 113), of whom 56 were cognitively stable and 57 progressed to AD with dementia during a 4- to 6-year follow-up, as well as 28 healthy controls who were followed up for 3 years. Main Outcome Measure During follow-up, 57 patients progressed to AD and 56 patients had stable MCI. Cerebrospinal fluid from these 2 groups of patients was compared using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. RESULTS: We identified a panel of 17 potential biomarkers that could distinguish between patients with stable MCI and patients with MCI who progressed to AD. We have positively identified and characterized 5 of the potential biomarkers. CONCLUSIONS: Proteomic profiling of cerebrospinal fluid provided a novel panel of 17 potential biomarkers for prediction of MCI progression to AD. The 5 identified biomarkers are relevant to the pathogenesis of AD and could help gain an understanding of the molecular pathways in which they may function. PMID- 17353379 TI - Voxel-based morphometry in frontotemporal lobar degeneration with ubiquitin positive inclusions with and without progranulin mutations. AB - BACKGROUND: Mutations in the progranulin gene (PGRN) have recently been identified as a cause of frontotemporal lobar degeneration with ubiquitin positive inclusions (FTLD-U) in some families. OBJECTIVE: To determine whether there is a difference in the patterns of atrophy in FTLD-U cases with and without PGRN mutations. DESIGN: Case-control study. SETTING: Brain bank of a tertiary care medical center. Patients Eight subjects who had screened positive for PGRN mutations (PGRN-positive) and who underwent volumetric magnetic resonance imaging were identified. Subjects were then matched by clinical diagnosis to a group of 8 subjects with a pathological diagnosis of FTLD-U who had screened negative for PGRN mutations (PGRN-negative). All subjects were then age-matched and sex matched to a control subject. MAIN OUTCOME MEASURES: Voxel-based morphometry was used to assess the patterns of gray matter atrophy in the PGRN-positive group compared with the PGRN-negative group and compared with controls. RESULTS: The PGRN-positive group showed a widespread and severe pattern of gray matter loss predominantly affecting the frontal, temporal, and parietal lobes. The PGRN negative group showed a less severe pattern of gray matter loss restricted mainly to the temporal and frontal lobes. On direct comparison, the PGRN-positive group showed greater gray matter loss in the frontal and parietal lobes compared with the PGRN-negative group. CONCLUSION: Findings from this study suggest that PGRN mutations may be associated with a specific and severe pattern of cerebral atrophy in subjects with FTLD-U. PMID- 17353380 TI - Cardiac valve regurgitation with pergolide compared with nonergot agonists in Parkinson disease. AB - BACKGROUND: Although most studies have suggested an increased risk of valvulopathy (primarily regurgitation) with pergolide mesylate use, one study suggested that this problem may also occur with use of the non-ergot-derived dopamine agonists pramipexole dihydrochloride and ropinirole hydrochloride. OBJECTIVE: To determine if cardiac valve regurgitation occurs more commonly in patients with Parkinson disease (PD) treated with pergolide than in those treated with nonergot agonists at a comparable dose. DESIGN: A case-control study of echocardiographic findings of valve function in patients receiving dopamine agonists for PD. SETTING: University-based referral center. Patients Thirty-six patients with idiopathic PD taking pergolide were compared with a matched control group of patients taking nonergot agonists with regard to the frequency and severity of cardiac valve regurgitation. Main Outcome Measure Valve scores (1 indicates trace; 2, mild; 3, moderate; and 4, severe) for the pergolide group were compared with those for the nonergot agonist control group. RESULTS: The mean +/- SD valve regurgitation scores in the matched pergolide group compared with the nonergot group were as follows: aortic, 0.83 +/- 1.23 vs 0.19 +/- 0.53 (P = .01); mitral, 1.42 +/- 1.0 vs 0.39 +/- 0.65 (P<.001); and tricuspid, 1.43 +/ 1.0 vs 0.19 +/- 0.53 (P<.001). Lifetime exposure to a dopamine agonist was not statistically different between the pergolide and nonergot agonist groups (P = .18). CONCLUSIONS: These data strengthen the conclusion that pergolide contributes to cardiac valve regurgitation when used in the long term as a treatment for PD. There appears to be low risk of cardiac valve regurgitation when using non-ergot-derived dopamine agonists. PMID- 17353381 TI - Adrenergic and vagal baroreflex sensitivity in autonomic failure. AB - BACKGROUND: The baroreflex is responsible for maintaining a stable blood pressure (BP) despite changes in body positions and fails in many autonomic disorders. The baroreflex regulates BP by changing the heart rate (vagal component) and total peripheral resistance (adrenergic component). Baroreflex sensitivity is widely used to quantify the vagal component of the reflex, but the adrenergic component is not quantifiable in the autonomic laboratory. OBJECTIVES: To develop and validate an index of adrenergic baroreflex sensitivity. DESIGN: We validated this index with microneurographically recorded muscle sympathetic nerve discharges generated by the Valsalva maneuver and verified it against groups of patients with graded severities of adrenergic failure. RESULTS: Adrenergic baroreflex sensitivity relates BP recovery time to the preceding decrease in BP evoked by the Valsalva maneuver. This index showed a graded and highly significant impairment in 3 groups of patients, (1) those with orthostatic hypotension (n = 26), (2) those with borderline orthostatic hypotension (n = 34), and (3) those with impaired reflex vasoconstriction without orthostatic BP change (n = 24), when compared with an age- and sex-matched control group (n = 29). Adrenergic baroreflex sensitivity better tracked the severity of adrenergic failure than the vagal component of baroreflex sensitivity and provides a much needed index to quantify total peripheral resistance changes in patients with adrenergic failure. CONCLUSIONS: The 2 indices of baroreflex sensitivity separately evaluate the vagal and adrenergic components of the baroreflex. Combined, they provide an index of composite or global baroreflex function. PMID- 17353382 TI - Body mass index and hospital discharge outcomes after ischemic stroke. AB - BACKGROUND: Obesity is a risk factor for vascular disease and has been associated with poorer outcomes in hospitalized patients. OBJECTIVE: To evaluate the relationship between body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) and discharge outcomes among persons hospitalized for ischemic stroke. METHODS: The relationship between BMI and discharge outcomes was analyzed in 805 consecutive patients with ischemic stroke admitted to a university hospital stroke service. Patients were categorized into 4 BMI categories representing lean, overweight, and class I and class II obesity. Outcome measures analyzed included discharge functional activity, direct discharge to home, and length of hospital stay. The independent effect of BMI on outcome was evaluated with regression analysis, adjusting for other variables known to predict outcome after ischemic stroke. RESULTS: Four hundred fifty-one individuals (56.0%) met study criteria. Mean age was 65 years, and 28.0% were men. In multivariate analysis, the highest BMI category (compared with lowest BMI category) was associated with the least likelihood of being discharged directly home from the hospital stroke service (26% vs 45%, P = .04), and the upper 2 BMI categories (compared with lowest BMI category) were associated with a trend toward extended length of hospital stay (6.3 vs 5.2 days, P = .08). No significant differences in the functional activity outcome were noted across BMI categories. CONCLUSIONS: Elevated BMI is associated with a lower likelihood of being discharged home and a trend toward extended hospital stay among patients hospitalized for ischemic stroke. Body mass index at hospital admission had no relation to discharge functional activity after stroke. PMID- 17353384 TI - Extensive and temporally ungraded retrograde amnesia in encephalitis associated with antibodies to voltage-gated potassium channels. AB - BACKGROUND: Encephalitis associated with antibodies to voltage-gated potassium channels (VGKC-Ab) is characterized by epilepsy, behavioral changes, and anterograde memory impairment. Magnetic resonance imaging reveals abnormal signal predominantly restricted to the mediotemporal lobes. OBJECTIVE: To determine the temporal extent and potential reversibility of retrograde amnesia in 3 patients with VGKC-Ab-associated encephalitis. DESIGN: Case report. SETTING: Clinical. Patients Three patients diagnosed as having VGKC-Ab-associated encephalitis underwent cognitive testing before and after immunotherapy. MAIN OUTCOME MEASURES: In addition to standard neuropsychological tests, retrograde memory was assessed using 2 novel tests. Memory for past newsworthy events was assessed using a public events test; test material was divided into epochs of 5 years and spanned approximately 25 years. This was complemented by a famous faces test in which patients were required to identify individuals from the recent and remote past. RESULTS: All 3 patients were found to have temporally ungraded retrograde amnesia dating back more than 20 years. Magnetic resonance imaging in all patients revealed high-signal abnormalities predominantly affecting the hippocampi. Subsequent testing performed after immunotherapy revealed subjective improvement but no evidence of a temporal gradient in the recovery of past memories. CONCLUSIONS: Encephalitis associated with VGKC-Ab results in extensive and temporally ungraded retrograde amnesia that is partially reversible with immunotherapy. Magnetic resonance imaging high-signal abnormalities were primarily restricted to the hippocampi. These data are supportive of theories postulating a role for the hippocampus in the storage and retrieval of all past memories, irrespective of age, rather than theories of memory consolidation that propose an involvement of the hippocampus only in the temporary storage of memories. PMID- 17353383 TI - Measures of adiposity and dementia risk in elderly persons. AB - BACKGROUND: Studies relating adiposity to dementia are conflicting. We explored the associations of body mass index (BMI), (calculated as weight in kilograms divided by the square of height in meters) waist circumference, and weight change to dementia, probable Alzheimer disease, and dementia associated with stroke (DAS). DESIGN: Persons without dementia were followed up for 5 years; 893 persons had BMI data, 907 had waist circumference data, and 709 had a second weight measurement. Dementia was ascertained using standard methods. Cox proportional hazards regression was used for analyses using follow-up as time to event, adjusting for demographics and apolipoprotein E-epsilon4 status. RESULTS: Compared with persons in the first quartile of BMI, persons in the third quartile had a lower dementia and Alzheimer disease risk and persons in the second quartile had a lower DAS risk. The association between BMI and dementia resembled a U shape in those younger than 76 years, while dementia risk decreased with higher BMI in those 76 years and older. The fourth quartile of waist circumference was related to a higher DAS risk in the whole sample, and to dementia and Alzheimer disease in persons younger than 76 years. Weight loss was related to a higher dementia and DAS risk, and weight gain was related to a higher DAS risk only. CONCLUSIONS: The prospective association between adiposity and dementia differs depending on the anthropometric measure used, and is modified by age. This may explain previous conflicting reports. PMID- 17353385 TI - Normal-appearing brain t1 relaxation time predicts disability in early primary progressive multiple sclerosis. AB - OBJECTIVE: To investigate whether patients with early primary progressive multiple sclerosis show changes in T1 relaxation time (T1-RT) in normal-appearing white matter (NAWM) and normal-appearing gray matter (NAGM) during 2 years and whether T1-RT at baseline predicts disability. METHODS: Twenty-one patients and 12 control subjects were studied at baseline and after 2 years. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores were assessed. T1 relaxation time histograms of NAWM and NAGM were obtained in all subjects, and mean, peak height, and peak location of the histograms were measured. Paired t tests were used to compare baseline and 2-year histogram values in patients and control subjects. To investigate whether T1-RT predicted clinical changes, multiple linear regression analysis was used. RESULTS: Patients showed increases in NAWM and NAGM T1-RT mean and peak location during follow-up, and significant decreases in NAWM and NAGM peak height. Baseline NAWM T1-RT mean values and peak height predicted disability at 2 years, as measured with the Multiple Sclerosis Functional Composite score. CONCLUSION: T1 relaxometry is a good marker of disease progression and has prognostic potential in primary progressive multiple sclerosis. PMID- 17353386 TI - Incidence of dementia in mild cognitive impairment in the cardiovascular health study cognition study. AB - OBJECTIVES: To examine the incidence of dementia in subjects with mild cognitive impairment (MCI) in the Cardiovascular Health Study Cognition Study. DESIGN: Prospective epidemiological study. SETTING: The Cardiovascular Health Study Cognition Study of Pittsburgh, Pa, was conducted from 2002 through 2003 to determine the incidence of dementia in participants classified as having MCI in 1998 and 1999. Subjects There were 136 subjects with MCI. Mild cognitive impairment was subclassified as MCI amnestic type and MCI multiple cognitive deficits type (MCI-MCDT); subjects with MCI-MCDT were also grouped based on the presence of a memory impairment. Subjects with MCI were classified as possible when there were comorbidities that could explain the subjects' cognitive deficits and as probable when there were none. Main Outcome Measure Dementia. RESULTS: The incidence of all dementias in the subjects with MCI was 147 per 1000 person-years (mean follow-up overall, 4.3 years). Of the 136 subjects with MCI, 69 (51%) in 1998 through 1999 progressed to dementia (57 [83%] to Alzheimer disease [AD]), but 25 (18%) returned to normal. Of the 10 subjects with probable MCI amnestic type, 7 (70%) progressed to dementia (all of them to AD) and none returned to normal, whereas 7 (41%) of the 17 subjects with possible MCI amnestic type became demented (6 [86%] to AD) and 3 (18%) returned to normal. Of the 40 subjects with probable MCI-MCDT, 21 (52%) progressed to dementia (17 [81%] to AD) and 2 (5%) returned to normal. Of the 69 subjects with possible MCI-MCDT, 34 (49%) progressed to dementia (28 [82%] to AD) and 20 (29%) returned to normal. Among the subjects with probable MCI-MCDT, 15 (54%) of 28 with and 6 (50%) of 12 without memory deficits progressed to dementia. CONCLUSIONS: Subjects with MCI are at high risk for dementia. The probable MCI diagnosis identified individuals in the earliest stages of dementia, usually AD, whereas the possible MCI diagnosis identified a more heterogeneous group. However, this latter group had only a slightly lower rate of conversion to dementia than the group with probable MCI, suggesting that even with comorbid conditions, there is a high likelihood of the presence of a progressive dementing disorder. PMID- 17353387 TI - A family with Parkinson disease, essential tremor, bell palsy, and parkin mutations. AB - BACKGROUND: Mutations in the parkin gene cause autosomal recessive early-onset Parkinson disease (EOPD). The A265G variant in the HS1 binding protein 3 gene (HS1BP3) is common in essential tremor (ET). OBJECTIVE: To investigate the presence of mutations in the parkin gene and the A265G variant in the HS1BP3 gene in a Mexican family with EOPD, ET, and Bell palsy. DESIGN: Direct sequencing, semiquantitative polymerase chain reaction, and reverse transcription-polymerase chain reaction were performed in the 14 members of this family. SETTING: Mexican family. Patients Two patients with EOPD were analyzed. RESULTS: Compound heterozygous mutations (EX 3_6 del and EX 5 del) in the parkin gene were identified in 2 patients with EOPD, characterized by beneficial response to levodopa, relatively slow progression, and motor complications. Although heterozygous EX 3_6 del and homozygous EX 5 del mutations in the parkin gene have been previously described, to our knowledge, this is the first report of these mutations in compound heterozygotes. Seven heterozygous A265G variants in the HS1BP3 gene were found in this pedigree, but they did not cosegregate with ET, Parkinson disease, or Bell palsy, supporting the conclusion that this variant is not associated with ET. CONCLUSIONS: Compound heterozygous parkin mutations (EX 3_6 del and EX 5 del) caused EOPD in this family, but the A265G variant in the HS1BP3 gene, previously considered to be responsible for ET, was probably not pathogenically related to the ET in this family. PMID- 17353388 TI - LRRK2 exon 41 mutations in sporadic Parkinson disease in Europeans. AB - BACKGROUND: Mutations in leucine-rich repeat kinase 2 gene (LRRK2), particularly the G2019S mutation in exon 41, have been detected in familial and sporadic Parkinson disease (PD) cases. OBJECTIVES: To assess the frequency of LRRK2 exon 41 mutations in a series of sporadic PD cases from Europe and to determine the clinical features of LRRK2 mutation carriers. DESIGN: We analyzed European cases of sporadic PD for the presence of LRRK2 exon 41 mutations. These mutations were screened by denaturing high-performance liquid chromatography, and abnormal chromatograph traces were investigated by direct sequencing to determine the exact nature of the variants. Early-onset sporadic PD cases were also screened for parkin mutations. The haplotypes associated with the G2019S mutation were determined. The clinical characteristics of patients carrying LRRK2 mutations were detailed. SETTING: French Network for the Study of Parkinson Disease Genetics. Patients Three hundred twenty patients with apparently sporadic PD from Europe. MAIN OUTCOME MEASURES: Results of genetic analyses. RESULTS: We found the G2019S mutation in 6 patients and identified 2 new variants (Y2006H and T2031S) in 1 patient each. Their clinical features were similar to those of typical PD. All G2019S mutation carriers shared a common haplotype. CONCLUSIONS: The G2019S mutation is almost as frequent in sporadic cases (1.9%) as in previously reported familial cases (2.9%) in Europe and occurs in the same common founder. We identified 2 novel variants. Although the phenotype of LRRK2 mutation carriers closely resembles that of typical PD, the age at onset was younger (29 years in 1 patient) than previously described, and 3 patients were improved by deep brain stimulation. PMID- 17353389 TI - Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. AB - OBJECTIVE: To determine the correspondence between uptake of Pittsburgh Compound B (PiB) in life and measures of beta-amyloid (Abeta) in postmortem tissue analysis. Patient A 76-year-old man with a clinical diagnosis of dementia with Lewy bodies underwent fluorodeoxyglucose (18)F and PiB positron emission tomographic brain scans. Imaging revealed marked region specific binding of PiB and abnormal fluorodeoxyglucose uptake. Intervention Autopsy was performed 3 months after the PiB scan. RESULTS: Autopsy confirmed the clinical diagnosis; in addition, there was severe cerebral amyloid angiopathy and only moderate numbers of parenchymal Abeta plaques. Biochemical measures revealed a positive correlation between Abeta levels and regional PiB binding. CONCLUSION: This report confirms that PiB detects Abeta in the living patient and demonstrates that amyloid deposited as cerebral amyloid angiopathy can be the dominant source of signal. PMID- 17353390 TI - Treatment of mitochondrial neurogastrointestinal encephalomyopathy with dialysis. AB - OBJECTIVE: To study the effect of continuous ambulatory peritoneal dialysis on nucleoside levels and clinical course in a patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Patient We studied a patient with genetically verified MNGIE, who prior to treatment had lost weight progressively, developed amenorrhea, vomited multiple times daily, and had abdominal pain. Intervention The patient was treated with peritoneal dialysis for 3 years, and the effect on symptoms and plasma concentrations of thymidine and deoxyuridine were monitored. RESULTS: Dialysis stopped vomiting and reduced abdominal pain, and the patient gained 5 kg in weight and started to menstruate again. Symptoms returned if dialysis was paused. Dialysis did not affect plasma nucleoside levels. CONCLUSIONS: This study shows an unambiguous clinical benefit of peritoneal dialysis on gastrointestinal symptoms in MNGIE. Dialysis did not affect nucleoside levels, indicating elevated thymidine and deoxyuridine levels are not solely responsible for the pathogenesis of MNGIE. PMID- 17353391 TI - Colorado surveillance program for chronic wasting disease transmission to humans: lessons from 2 highly suspicious but negative cases. AB - OBJECTIVE: To describe 2 patients with rapidly progressive dementia and risk factors for exposure to chronic wasting disease (CWD) in whom extensive testing negated the possible transmission of CWD. Design/ METHODS: We describe the evaluation of 2 young adults with initial exposure histories and clinical presentations that suggested the possibility of CWD transmission to humans. Patients A 52-year-old woman with possible laboratory exposure to CWD and a 25 year-old man who had consumed meat from a CWD endemic area. INTERVENTIONS: Clinical evaluation, neuropathological examination, and genetic testing. RESULTS: Neuropathological and genetic assessment in the 2 patients proved the diagnoses of early-onset Alzheimer disease and a rare genetic prion disease. CONCLUSION: No convincing cases of CWD transmission to humans have been detected in our surveillance program. PMID- 17353392 TI - Right anterior cingulate cortex infarction and transient speech aspontaneity. AB - BACKGROUND: According to recent functional studies, the medial frontal lobe of the dominant hemisphere plays a role in both word generation and speech initiation. To our knowledge, speech arrest with intact facial expression secondary to the right anterior cingulate cortex (ACC) lesion has not been previously reported. OBJECTIVE: To report 2 cases of speech initiation difficulties associated with a stroke of the right anterior cingulate gyrus with magnetic resonance imaging with tractography results. DESIGN: Two case reports. SETTING: Inpatient neurology clinic at a university medical center. Patients Two women who had acute and transient speech initiation problems. RESULTS: Speech evaluation revealed pure speech initiation difficulties with intact facial praxis and expression. In the patient who could be tested, writing ability was preserved. In addition to acute right ACC infarction, the magnetic resonance imaging also revealed anterior corpus callosum and/or posterior corpus callosum involvement. Tractography in patient 2 revealed fibers from the right ACC that would cross to the contralateral side. Reduced fiber numbers connecting the right supplementary motor area with the ACC were also observed, which differed from the left ACC tractography. CONCLUSIONS: To our knowledge, this is the first case series of right ACC stroke with transient speech initiation problems. Because of the rare findings of the tractography, we suggest that in some patients, speech initiation required the participation of the right ACC in addition to the language network of the left hemisphere. PMID- 17353393 TI - Acute carpal tunnel syndrome preceded by 5 years of unusual skin changes. PMID- 17353394 TI - Oculosympathetic paratrigeminal paralysis with isolated v2 involvement in carotid artery dissection. PMID- 17353395 TI - Early abnormality of diffusion-weighted magnetic resonance imaging followed by brain atrophy in a case of Gerstmann-Straussler-Scheinker disease. PMID- 17353396 TI - Changes in PDE4D isoforms in the hippocampus of a patient with advanced Alzheimer disease. PMID- 17353397 TI - Adverse reactions to anthrax vaccine (eg, optic neuritis) may be more complex or delayed than reported initially by Payne et al (2006). PMID- 17353398 TI - Slower disease progression and prolonged survival in contemporary patients with amyotrophic lateral sclerosis. PMID- 17353399 TI - High-sensitivity C-reactive protein, other markers of inflammation, and the incidence of macular degeneration in women. AB - OBJECTIVE: To investigate whether high-sensitivity C-reactive protein (hsCRP) and other biomarkers of inflammation predict age-related macular degeneration (AMD). METHODS: We measured hsCRP, soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen levels in baseline plasma samples from 27 687 participants with a mean age of 54.6 years and initially free of AMD in the Women's Health Study. We prospectively ascertained 150 cases of AMD with vision loss of 20/30 or worse in the affected eye by self-report confirmed with review of medical records during 275 852 person-years of follow-up (mean = 10 years) and used proportional hazards models to examine the relationship between these biomarkers and AMD. RESULTS: After adjustment for multiple risk factors, the hazard ratio (HR) (95% confidence interval [CI]) of AMD, contrasting the highest vs lowest quintile of hsCRP, was 3.09 (1.39-6.88) (P trend = .02). In similar models, the HR (95% CI) for sICAM-1 was 1.87 (0.97-3.58) (P trend = .07). The relationship between fibrinogen and AMD was J-shaped, with an HR (95% CI) of 2.01 (1.07-3.75) for women in the highest fifth vs second fifth. CONCLUSION: Elevated circulating levels of hsCRP, sICAM-1, and fibrinogen precede the development of visually significant AMD in women, providing further support for the hypothesis that inflammation may play a role in AMD. PMID- 17353400 TI - Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. AB - OBJECTIVE: To evaluate a dexamethasone intravitreous drug delivery system (DDS) in patients with persistent (> or =90 days despite treatment) macular edema. METHODS: This 6-month study randomized 315 patients with persistent macular edema with best-corrected visual acuity (BCVA) of 20/40 to 20/200 in the study eye to observation or a single treatment with dexamethasone DDS, 350 or 700 microg. MAIN OUTCOME MEASURES: Proportion of patients achieving a BCVA improvement of 10 or more letters or 15 or more letters, safety measures, change in fluorescein angiographic leakage, and central retinal thickness. RESULTS: At day 90 (primary end point), an improvement in BCVA of 10 letters or more was achieved by a greater proportion of patients treated with dexamethasone DDS, 700 microg (35%) or 350 microg (24%), than observed patients (13%; P<.001 vs 700-microg group; P = .04 vs 350-microg group); an improvement in BCVA of 15 letters or more was achieved in 18% of patients treated with dexamethasone DDS, 700 microg, vs 6% of observed patients (P = .006). Results were similar in patients with diabetic retinopathy, vein occlusion, or uveitis or Irvine-Gass syndrome. During 3 months of observation, 11% of treated patients and 2% of observed patients had intraocular pressure increases of 10 mm Hg or higher. CONCLUSION: In persistent macular edema, a single dexamethasone DDS treatment produced statistically significant BCVA improvements 90 days after treatment and was well tolerated for 180 days. Application to Clinical Practice Dexamethasone DDS, 700 microg, may have potential as a treatment for persistent macular edema. PMID- 17353401 TI - Effect of ruboxistaurin in patients with diabetic macular edema: thirty-month results of the randomized PKC-DMES clinical trial. AB - OBJECTIVE: To evaluate the safety and efficacy of orally administered ruboxistaurin (RBX) as a mesylate salt in patients with diabetic macular edema (DME). DESIGN: Multicenter, double-masked, randomized, placebo-controlled study of 686 patients receiving placebo or RBX orally (4, 16, or 32 mg/d) for 30 months. At baseline, patients had DME farther than 300 mum from the center of the macula, an Early Treatment Diabetic Retinopathy Study retinopathy severity level from 20 to 47A without prior photocoagulation, and an Early Treatment Diabetic Retinopathy Study visual acuity of 75 or more letters in the study eye. The primary study outcome was progression to sight-threatening DME or application of focal/grid photocoagulation for DME. Main Outcome Measure Masked grading of stereoscopic fundus photographs. RESULTS: The delay in progression to the primary outcome was not statistically significant (32 mg of RBX vs placebo, P = .14 [unadjusted]; Cox proportional hazards model adjusted for covariates, hazards ratio = 0.73; 95% confidence interval, 0.53-1.0; P = .06). However, application of focal/grid photocoagulation prior to progression to sight-threatening DME varied by site, and a secondary analysis of progression to sight-threatening DME alone showed that 32 mg of RBX per day reduced progression, compared with placebo (P = .054 [unadjusted]; Cox proportional hazards model, hazards ratio = 0.66; 95% confidence interval, 0.47-0.93; P = .02). CONCLUSIONS: Although progression to the primary outcome was not delayed, daily oral administration of RBX may delay progression of DME to a sight-threatening stage. Ruboxistaurin was well tolerated in this study. PMID- 17353402 TI - Internal limiting membrane peeling with indocyanine green or trypan blue in macular hole surgery: a randomized trial. AB - OBJECTIVE: To report on anatomical and visual outcomes after vitrectomy and internal limiting membrane peeling for idiopathic macular hole repair. METHODS: Forty patients with stage II to IV idiopathic macular holes were randomly assigned (1:1) in a 2-arm, single-center, randomized controlled . Internal limiting membrane delamination was performed using indocyanine green (ICG) solution (n = 20) or trypan blue (TB) (n = 20). Two patients did not complete the study, for a total of 19 in each group. Follow-up examinations included Early Treatment of Diabetic Retinopathy Study visual acuity, scanning laser ophthalmoscope microperimetry, optical coherence tomography, and fluorescein angiography. Main Outcome Measure Visual acuity 3 months after surgery. RESULTS: Visual acuity did not show a significant difference between study groups (95% confidence interval [CI], -2 to 1 lines). The rate of macular hole closures was identical (84%; 95% CI, 60% to 97%). Within-group visual recovery was significant only in the TB group. Central scotomata despite hole closure persisted in 8 patients (42%) in the ICG group and in 5 (26%) in the TB group. CONCLUSION: Although no statistically significant difference was detected for the primary end point, the better visual recovery in the TB group and the higher rate of persistent central scotomata in the ICG group justify a larger clinical trial. Application to Clinical Practice No statistically significant difference in visual acuity between ICG and TB in the used concentrations and application method could be proved in macular hole surgery. PMID- 17353403 TI - Beta carotene supplementation and age-related maculopathy in a randomized trial of US physicians. AB - OBJECTIVE: To test whether beta carotene supplementation affects the incidence of age-related maculopathy (ARM) in a large-scale randomized trial. DESIGN: Randomized, double-masked, placebo-controlled trial among 22 071 apparently healthy US male physicians aged 40 to 84 years. Participants were randomly assigned to receive beta carotene (50 mg every other day) or placebo. Main Outcome Measure Incident ARM responsible for a reduction in best-corrected visual acuity to 20/30 or worse. RESULTS: After 12 years of treatment and follow-up, there were 162 cases of ARM in the beta carotene group vs 170 cases in the placebo group (relative risk [RR], 0.96; 95% confidence interval [CI], 0.78 1.20). The results were similar for the secondary end points of ARM with or without vision loss (275 vs 274 cases; RR, 1.01; 95% CI, 0.86-1.20) and advanced ARM (63 vs 66 cases; RR, 0.97; 95% CI, 0.69-1.37). CONCLUSIONS: These randomized data relative to 12 years of treatment among a large population of apparently healthy men indicate that beta carotene supplementation has no beneficial or harmful effect on the incidence of ARM. Long-term supplemental use of beta carotene neither decreases nor increases the risk of ARM. PMID- 17353404 TI - Detecting visual function abnormalities using the Swedish interactive threshold algorithm and matrix perimetry in eyes with glaucomatous appearance of the optic disc. AB - OBJECTIVE: To compare the ability of 24-2 frequency-doubling perimetry (FDP Matrix) with standard automated perimetry with the Swedish interactive threshold algorithm (SAP-SITA) in detection of visual function abnormalities in patients with glaucomatous-appearing optic discs (GAOD). METHODS: This observational case control study included 80 patients with GAOD and 54 control subjects diagnosed by masked assessment of optic disc stereoscopic photographs. Abnormal visual function at SAP-SITA and FDP-Matrix testing required consistent abnormalities in 2 visual field examinations, determined using the glaucoma hemifield test outside 99% normal limits, pattern standard deviation outside 95% normal limits, or 3 contiguous points in the pattern deviation probability plot outside 95% normal limits (at least 1 P<1%) within the same hemifield. RESULTS: The FDP-Matrix and SAP-SITA detected abnormal visual function in 51% and 44%, respectively, of GAOD eyes (P = .26), and both perimetry techniques identified 11% of healthy eyes as abnormal. Agreement between FDP-Matrix and SAP-SITA was moderate (kappa = 0.49), as only 35% of GAOD eyes and 2% of healthy eyes had both visual field test results flagged as abnormal. CONCLUSIONS: The FDP-Matrix detected abnormal visual function in more eyes with GAOD than did SAP-SITA, although this difference was not significant. Each visual field test tended to identify different subsets of eyes with GAOD as abnormal. Combination of these perimetry techniques may improve the detection of visual function abnormalities in patients with glaucoma. PMID- 17353405 TI - Optic nerve hydropic axonal degeneration and blocked retrograde axoplasmic transport: histopathologic features in human high-pressure secondary glaucoma. AB - OBJECTIVE: To describe histopathologic features of anterior optic nerves of 12 eyes enucleated for sustained high ocular pressure from iris-ciliary body melanomas in 10 and choroidal melanomas with chronic angle closure in 2. METHODS: In this retrospective study, we analyzed cases indexed in 2 eye pathology laboratories and reviewed the pertinent literature. Cases were identified from diagnostic indexes; microscopic study of slides stained with hematoxylin-eosin and Verhoeff-van Gieson, Mallory trichrome, periodic acid-Schiff, alcian blue, or colloidal iron for acid mucopolysaccharide; review of available clinical documentation; and analysis of features and photography. The main outcome measures were description of optic nerve heads, prelaminar atrophy, laminar posterior bowing, locations and density of hydropic axonal degeneration, blocked retrograde axoplasmic transport, posterior atrophy, and optic nerve disorganization with glial proliferation. RESULTS: Hydropic axonal degeneration was present in front of, within, and posterior to the lamina cribrosa in all 12 eyes. This degeneration extended diffusely and posteriorly from the peripheral lamina and was most dense centrally in 10 eyes. Retrolaminar changes compatible with blockage of retrograde axoplasmic transport were seen in 9 eyes. Posterior atrophy with disorganization and glial proliferation was seen in 10 eyes. No eye had classic glaucomatous atrophic cupping. CONCLUSIONS: Diffuse and centrally intense hydropic axonal degeneration and central blocked retrograde axoplasmic transport explain loss of central acuity, generalized contraction of visual field, and generalized optic atrophy without glaucomatous cupping in eyes with prolonged high-pressure secondary glaucoma. PMID- 17353406 TI - Primary intraocular lens implantation in pediatric uveitis: a comparison of 2 populations. AB - OBJECTIVE: To evaluate the visual outcome and postoperative complications of cataract surgery with posterior chamber intraocular lens implantation in children with uveitis. DESIGN: A multicenter, retrospective, interventional case series. The setting included 3 medical centers in Israel. The interventions were cataract surgery and intraocular lens implantation. Aggressive preoperative and postoperative systemic and topical anti-inflammatory treatment was instituted. The main outcome measures included postoperative inflammation, complications, and visual outcome. RESULTS: Children with juvenile rheumatoid arthritis (JRA) associated uveitis were seen and underwent cataract surgery at an earlier age, and had a lower preoperative visual acuity and more severe uveitic complications when first seen, than those with non-JRA-associated uveitis. Visual acuity improved by 2 or more lines in all patients, and in 13 eyes the final visual acuity was 20/40 or better. Postoperative complications included elevated intraocular pressure, posterior and anterior capsular opacities, and macular dysfunction. CONCLUSIONS: Compared with those with non-JRA-associated uveitis, children with JRA-associated uveitis tend to have more severe manifestations of disease when first seen and after surgery, but there is no significant difference in postoperative course or complications. Intraocular lens implantation, including small-incision, foldable, intraocular lenses, is well tolerated, when combined with aggressive medical treatment, for controlling inflammation. We believe that intraocular lens implantation is not contraindicated in those with pediatric uveitis, including uveitis associated with JRA. PMID- 17353407 TI - Objective structured assessment of cataract surgical skill. AB - OBJECTIVE: To evaluate the Objective Structured Assessment of Cataract Surgical Skill scoring system. METHODS: An objective performance rating tool was devised. This instrument is comprised of standardized criteria with global rating and operation-specific components, each rated on a 5-point Likert scale. The total potential score was 100. Complete phacoemulsification cataract extraction operations were recorded through the operating microscope of surgeons with a range of experience (group A, <50 procedures; group B, 50-249 procedures; group C, 250-500 procedures, and group D, >500 procedures). These were then scored by independent expert reviewers masked to the grades of the surgeons. The U test was used to evaluate statistical significance. RESULTS: We evaluated 38 surgical videotapes of 38 surgeons (group A, 11 surgeons; group B, 10 surgeons; group C, 5 surgeons; and group D, 12 surgeons). Mean +/- SD overall scores were as follows: group A, 32.0 +/- 5.3; group B, 55.0 +/- 12.6; group C, 89.0 +/- 4.7; and group D, 90.0 +/- 11.1. Statistically significant differences were found between groups A and B (P = .002) and groups B and C (P = .003), but not between groups C and D (P>.99). CONCLUSION: The Objective Structured Assessment of Cataract Surgical Skill scoring system seems to have construct validity with cataract surgery and, thus, may be valuable for assessing the surgical skills of junior trainees. PMID- 17353408 TI - Incomitant esotropia following pterygium excision surgery. AB - OBJECTIVE: To report the clinical characteristics and treatment of subjects with incomitant esotropia following unilateral pterygium excision. METHODS: A retrospective review of 6 consecutive patients who developed incomitant esotropia, limited abduction, and diplopia following unilateral pterygium excision surgery. RESULTS: The mean preoperative deviation was 6 prism diopters (PD) (range, 0-25 PD) in the primary position and 13.8 PD (range, 6-25 PD) in the abducting field of the involved eye. Four patients underwent simultaneous surgery on the conjunctiva-perimuscular connective tissue complex and the medial rectus muscle. One subject had conjunctival-perimuscular connective tissue complex surgery alone. Postoperatively, all patients had orthotropia in the primary position and the deviation in the abducting field was improved to 5.2 PD (range, 0-14 PD). CONCLUSIONS: Incomitant esotropia is an uncommon but serious complication following pterygium excision surgery. Medial rectus muscle recession combined with scar tissue removal is required to eliminate diplopia in the primary position. Conjunctiva-perimuscular scar tissue removal may suffice to improve diplopia in the abduction gaze position. PMID- 17353409 TI - Transcaruncular medial canthal ligament plication for repair of lower eyelid malposition. AB - OBJECTIVE: To evaluate the long-term efficacy of transcaruncular medial canthal ligament (MCL) plication in the treatment of eyelid malposition. METHODS: Transcaruncular MCL plication was performed on 176 eyelids of 125 patients with symptomatic ocular exposure due to lower eyelid malposition in which MCL laxity was an important component. Preoperative and postoperative ocular exposure symptoms, lower eyelid position, lagophthalmos, and keratopathy were compared. RESULTS: At an average +/- SD follow-up time of 25 +/- 27 months (range, 1-103 months), 88% of preoperative symptoms resolved or improved. Lower eyelid position (P<.001), lagophthalmos (P<.001), and keratopathy (P<.001) were significantly improved. In 11% of eyelids undergoing MCL plication as the only repair, results were comparable with those in which other repairs were performed concurrently. Complications were suture breakage in 2 cases and pyogenic granuloma in 1 case. CONCLUSIONS: Transcaruncular MCL plication is a safe and effective technique for MCL laxity that contributes to lower eyelid malposition. This minimally invasive technique achieves good functional and cosmetic outcomes by re-establishing the vectoral forces for eyelid support that are normally provided by the tripartite ligament. PMID- 17353410 TI - Green bone. AB - OBJECTIVE: To describe the unusual finding of yellow-green-colored bone during routine orbital surgery, to detail its investigation, and to demonstrate its benign nature. METHODS: When green bone was found, specimens were sent for light and fluorescent microscopy, ultraviolet photography, and spectrophotometry. RESULTS: Yellow-green bone was encountered in 3 patients during orbital tumor excision or orbital fracture repair procedures. The only common cause was prior use of tetracycline during adolescence. All patients had healthy white dentition. In all cases, absence of neoplasia was demonstrated histologically. The bone fluoresced with a bright yellow-green color when exposed to 365-nm ultraviolet light. Histologic analysis demonstrated fluorescence located near the haversian canals. Spectrophotometry revealed absorption at 4 wavelengths specific to tetracycline: 230, 275, 380, and 440 nm. CONCLUSIONS: Fixation of tetracycline and ensuing fluorescence occurs mostly in areas of new bone growth and mineralization. This happens during childhood but also with bone remodeling associated with tumors or fractures. Once mineralized, teeth should therefore not be affected if tetracycline exposure occurs after ages 8 to 10 years. This paucity of external clues can lead to the surprising but innocuous surgical finding of green bone. Careful history and proper investigation can confirm its origin. PMID- 17353411 TI - Ocular pathologic findings of neurofibromatosis type 2. AB - OBJECTIVE: To gain insight into the pathogenesis of neurofibromatosis type 2 (NF2) by investigating the ocular manifestations of this disease. METHODS: Using standard histologic techniques, immunohistochemistry, and electron microscopy, we described the ocular pathologic findings of a 34-year-old woman who died from complications of NF2. RESULTS: We identified 3 types of NF2-associated lesions: juvenile posterior subcapsular cataracts, epiretinal membranes, and an intrascleral schwannoma. CONCLUSIONS: Our analysis indicated that dysplastic lens cells accumulate just anterior to the posterior lens capsule in juvenile posterior subcapsular cataracts and that dysplastic Muller cells may be a major component of NF2-associated epiretinal membranes. Clinical Relevance Our findings suggest that a subset of glial cells with epithelial features (Schwann cells, ependymal cells, and Muller cells) may be particularly sensitive to loss of the NF2 gene. Understanding the molecular basis for this sensitivity may lead to novel strategies for treating NF2. PMID- 17353412 TI - Assessing surgical competence in ophthalmology training programs. PMID- 17353413 TI - Global access to eye care. PMID- 17353414 TI - Nuclear cataract: do statins reduce risk? PMID- 17353415 TI - Access to eye care: response of the American Academy of Ophthalmology and its members to societal needs now and in the future. PMID- 17353416 TI - Access to care: eye care provider workforce considerations in 2020. PMID- 17353417 TI - Eye care in the United States: do we deliver to high-risk people who can benefit most from it? AB - OBJECTIVE: To estimate the levels of self-reported access of eye care services in the nation. METHODS: We analyzed data from the 2002 National Health Interview Survey (30 920 adults aged > or =18 years). We estimated the number of US adults at high risk for serious vision loss and assessed factors associated with the use of eye care services. RESULTS: An estimated 61 million adults in the United States were at high risk for serious vision loss (they had diabetes, had vision or eye problems, or were aged > or =65 years); 42.0% of the 78 million adults who had dilated eye examinations in the past 12 months were among this group. Among the high-risk population, the probability of having a dilated eye examination increased with age, education, and income (P<.01). The probability of receiving an examination was higher for the insured, women, persons with diabetes, and those with vision or eye problems (P<.01). Approximately 5 million high-risk adults could not afford eyeglasses when needed; being female, having low income, not having insurance, and having vision or eye problems were each associated with such inability (P<.01). CONCLUSIONS: There is substantial inequity in access to eye care in the United States. Better targeting of resources and efforts toward people at high risk may help reduce these disparities. PMID- 17353418 TI - New lacrimal cannula for probing and irrigation in the tearing patient. AB - Katena cannula K7-3016 (Katena Products, Inc, Denville, NJ) is a 23-gauge cannula that features an end-opening port for direct irrigation and a tapered tip for ease of entry into an undilated punctum. The 13-mm length makes it ideal to probe as well as irrigate the proximal lacrimal system. Katena cannula K7-3016 eliminates the need for punctal dilation and placement of Bowman probes to dilate the punctum and measure canalicular obstruction, respectively. The end-opening, direct irrigation design prevents misdiagnosis in the setting of canalicular stenosis. PMID- 17353419 TI - Warfarin-induced skin necrosis of the eyelids. PMID- 17353420 TI - Bilateral orbital infarction syndrome after bifrontal craniotomy. PMID- 17353421 TI - Solitary fibrous tumor of the conjunctiva. PMID- 17353422 TI - Ciliary body melanoma simulating multiple iris cysts. PMID- 17353423 TI - Quinine iris toxicity. PMID- 17353424 TI - Familial exudative vitreoretinopathy and osteoporosis-pseudoglioma syndrome caused by a mutation in the LRP5 gene. PMID- 17353426 TI - Trans-lamina cribrosa pressure difference. PMID- 17353427 TI - Osteoporosis-pseudoglioma syndrome may not be caused by persistent fetal vasculature. PMID- 17353428 TI - Persistent fetal vasculature. PMID- 17353429 TI - Management of orbital compartment syndrome. PMID- 17353431 TI - No association between variations in the WDR36 gene and primary open-angle glaucoma. PMID- 17353433 TI - Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. PMID- 17353434 TI - Noninvasive evaluation of coronary sinus anatomy and its relation to the mitral valve annulus: implications for percutaneous mitral annuloplasty. AB - BACKGROUND: Percutaneous mitral annuloplasty has been proposed as an alternative to surgical annuloplasty. In this respect, evaluation of the coronary sinus (CS) and its relation with the mitral valve annulus (MVA) and the coronary arteries is relevant. The feasibility of evaluating these issues noninvasively with multislice computed tomography was determined. METHODS AND RESULTS: In 105 patients (72 men, age 59+/-11 years), 64-slice multislice computed tomography was performed for noninvasive evaluation of coronary artery disease. Thirty-four patients with heart failure and/or severe mitral regurgitation were included. Three-dimensional reconstructions and standard orthogonal planes were used to assess CS anatomy and its relation with the MVA and circumflex artery. In 71 patients (68%), the circumflex artery coursed between the CS and the MVA with a minimal distance between the CS and the circumflex artery of 1.3+/-1.0 mm. The CS was located along the left atrial wall, rather than along the MVA, in the majority of the patients (ranging from 90% at the level of the MVA to 14% at the level of the distal CS). The minimal distance between the CS and MVA was 5.1+/ 2.9 mm. In patients with severe mitral regurgitation, the minimal distance between the CS and the MVA was significantly greater as compared with patients without severe mitral regurgitation (mean 7.3+/-3.9 mm versus 4.8+/-2.5 mm, P<0.05). CONCLUSIONS: In the majority of the patients, the CS courses superiorly to the MVA. In 68% of the patients, the circumflex artery courses between the CS and the mitral annulus. Multislice computed tomography may provide useful information for the selection of potential candidates for percutaneous mitral annuloplasty. PMID- 17353435 TI - Cardioprotection by ecto-5'-nucleotidase (CD73) and A2B adenosine receptors. AB - BACKGROUND: Ecto-5'-nucleotidase (CD73)-dependent adenosine generation has been implicated in tissue protection during acute injury. Once generated, adenosine can activate cell-surface adenosine receptors (A1 AR, A2A AR, A2B AR, A3 AR). In the present study, we define the contribution of adenosine to cardioprotection by ischemic preconditioning. METHODS AND RESULTS: On the basis of observations of CD73 induction by ischemic preconditioning, we found that inhibition or targeted gene deletion of cd73 abolished infarct size-limiting effects. Moreover, 5' nucleotidase treatment reconstituted cd73-/- mice and attenuated infarct sizes in wild-type mice. Transcriptional profiling of adenosine receptors suggested a contribution of A2B AR because it was selectively induced by ischemic preconditioning. Specifically, in situ ischemic preconditioning conferred cardioprotection in A1 AR-/-, A2A AR-/-, or A3 AR-/- mice but not in A2B AR-/- mice or in wild-type mice after inhibition of the A2B AR. Moreover, A2B AR agonist treatment significantly reduced infarct sizes after ischemia. CONCLUSIONS: Taken together, pharmacological and genetic evidence demonstrate the importance of CD73-dependent adenosine generation and signaling through A2B AR for cardioprotection by ischemic preconditioning and suggests 5'-nucleotidase or A2B AR agonists as therapy for myocardial ischemia. PMID- 17353436 TI - Prevalence and prognostic significance of heart failure stages: application of the American College of Cardiology/American Heart Association heart failure staging criteria in the community. AB - BACKGROUND: Heart failure (HF) is a progressive disorder associated with frequent morbidity and mortality. An American Heart Association/American College of Cardiology staging classification of HF has been developed to emphasize early detection and prevention. The prevalence of HF stages and their association with mortality are unknown. We sought to estimate HF stage prevalence in the community and to measure the association of HF stages with mortality. METHODS AND RESULTS: A population-based, cross-sectional, random sample of 2029 Olmsted County, Minnesota, residents aged > or = 45 years was identified. Participants were classified by medical record review, symptom questionnaire, physical examination, and echocardiogram as follows: stage 0, healthy; stage A, HF risk factors; stage B, asymptomatic cardiac structural or functional abnormalities; stage C, HF symptoms; and stage D, severe HF. In the cohort, 32% were stage 0, 22% stage A, 34% stage B, 12% stage C, and 0.2% stage D. Mean B-type natriuretic peptide concentrations (in pg/mL) increased by stages: stage 0=26, stage A=32, stage B=53, stage C=137, and stage D=353. Survival at 5 years was 99% in stage 0, 97% in stage A, 96% in stage B, 75% in stage C, and 20% in stage D. CONCLUSIONS: The present study provides prevalence estimates and prognostic validation for HF staging in a community cohort. Of note, 56% of adults > or = 45 years of age were classified as being in stage A (risk factors) or B (asymptomatic ventricular dysfunction). HF staging underscores the magnitude of the population at risk for progression to overt HF. PMID- 17353437 TI - High prevalence of sleep apnea syndrome in patients with long-term pacing: the European Multicenter Polysomnographic Study. AB - BACKGROUND: Cardiovascular diseases leading to pacemaker implantations are suspected of being associated with a high rate of undiagnosed sleep apnea syndrome (SAS). We sought to determine the prevalence and consequences of SAS in pacemaker patients according to pacing indications: heart failure, symptomatic diurnal bradycardia, and atrioventricular block. METHODS AND RESULTS: Ninety eight consecutive patients (mean age, 64+/-8 years) not known to have sleep apnea were included; 29 patients were paced for dilated cardiomyopathy (29%), 33 for high-degree atrioventricular block (34%), and 36 for sinus node disease (37%). All underwent Epworth Sleepiness Scale assessment and polysomnography with the pacemaker programmed to right ventricular DDI pacing mode (lower pacing rate, 50 pulses per minute). SAS was defined as an apnea-hypopnea index > or = 10/h. Mean Epworth Sleepiness Scale was in the normal range (7+/-4), although 13 patients (25%) had an abnormal score > 11/h. Fifty-seven patients (59%) had SAS; of these, 21 (21.4%) had a severe SAS (apnea-hypopnea index > 30/h). In patients with heart failure, 50% presented with SAS (mean apnea-hypopnea index, 11+/-7) compared with 68% of patients with atrioventricular block (mean apnea-hypopnea index, 24+/-29) and 58% with sinus node disease (mean apnea-hypopnea index, 19+/-23). CONCLUSIONS: In paced patients, there is an excessively high prevalence of undiagnosed SAS (59%). Whether treating SAS would have changed the need for pacing is unknown. Treatment effects should be further evaluated particularly because these patients are less symptomatic than typical SAS patients. In any case, SAS should be systematically searched for in paced patients owing to potential detrimental effects on their cardiovascular evolution. PMID- 17353438 TI - Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study. AB - BACKGROUND: Marked reductions in cardiovascular disease (CVD) morbidity and mortality have occurred in the United States over the last 50 years. We tested the hypothesis that the relative burden of CVD attributable to diabetes mellitus (DM) has increased over the past 5 decades. METHODS AND RESULTS: Participants aged 45 to 64 years from the Framingham Heart Study, who attended examinations in an "early" time period (1952 to 1974), were compared with those who attended examinations in a later time period (1975 to 1998). The risk of CVD events (n=133 among those with and 1093 among those without DM) attributable to DM in the 2 time periods was assessed with Cox proportional hazards models; population attributable risk of DM as a CVD risk factor was calculated for each time period. The age- and sex-adjusted hazard ratio for DM as a CVD risk factor was 3.0 (95% CI, 2.3 to 3.9) in the earlier time period and 2.5 (95% CI, 1.9 to 3.2) in the later time period. The population attributable risk for DM as a CVD risk factor increased from 5.4% (95% CI, 3.8% to 6.9%) in the earlier time period to 8.7% (95% CI, 5.9% to 11.4%) in the later time period (P for attributable risk ratio=0.04), although multivariable adjustment resulted in attenuation of these findings (P=0.12); most of these observations were found among men. CONCLUSIONS: The proportion of CVD attributable to DM has increased over the past 50 years in Framingham. These findings emphasize the need for increased efforts to prevent DM and to aggressively treat and control CVD risk factors among those with DM. PMID- 17353439 TI - Amplified expression profiling of platelet transcriptome reveals changes in arginine metabolic pathways in patients with sickle cell disease. AB - BACKGROUND: In sickle cell disease, ischemia-reperfusion injury and intravascular hemolysis produce endothelial dysfunction and vasculopathy characterized by reduced nitric oxide and arginine bioavailability. Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, which suggests that pathological platelet activation may contribute to sickle cell disease vasculopathy. METHODS AND RESULTS: Studies were therefore undertaken to examine transcriptional signaling pathways in platelets that may be dysregulated in sickle cell disease. We demonstrate and validate in the present study the feasibility of comparative platelet transcriptome studies on clinical samples from single donors by the application of RNA amplification followed by microarray-based analysis of 54,000 probe sets. Data mining an existing microarray database, we identified 220 highly abundant genes in platelets and a subset of 72 relatively platelet-specific genes, defined by >10-fold increased expression compared with the median of other cell types in the database with amplified transcripts. The highly abundant platelet transcripts found in the present study included 82% or 70% of platelet-abundant genes identified in 2 previous gene expression studies on nonamplified mRNA from pooled or apheresis samples, respectively. On comparing the platelet gene expression profiles in 18 patients with sickle cell disease in steady state to those of 12 black control subjects, at a 3-fold cutoff and 5% false-discovery rate, we identified approximately 100 differentially expressed genes, including multiple genes involved in arginine metabolism and redox homeostasis. Further characterization of these pathways with real-time polymerase chain reaction and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels. CONCLUSIONS: The present studies suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease and provide a novel framework for the study of disease specific platelet biology. PMID- 17353440 TI - Six-month outcome of emergency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction. AB - BACKGROUND: The outcome of resuscitated patients after cardiac arrest complicating acute myocardial infarction remains poor, primarily because of the relatively low success rates of cardiopulmonary resuscitation management. Existing data suggest potential beneficial effects of early myocardial reperfusion, but the predictors of survival in these patients remain unknown. METHODS AND RESULTS: From 1995 to 2005, 186 patients (78% men; mean age, 60.4+/ 13.8 years) underwent immediate percutaneous coronary intervention after successful resuscitation for cardiac arrest complicating acute myocardial infarction. Prompt prehospital management was performed by mobile medical care units in 154 of 186 patients, whereas 32 had in-hospital cardiac arrest. Infarct location was anterior in 105 patients (56%), and shock was present on admission in 96 (52%). Percutaneous coronary intervention (stenting rate 90%) was successful in 161 of 186 patients (87%). Six-month survival rate was 100 of 186 (54%), and 6-month survival free of neurological sequelae was 46%. By multivariate analysis, predictors of 6-month survival were a shorter interval between the onset of cardiac arrest and arrival of a first responder (odds ratio, 0.67; 95% CI, 0.54 to 0.84), a shorter interval between the onset of cardiac arrest and return of spontaneous circulation (odds ratio, 0.91; 95% CI, 0.87 to 0.96), and absence of diabetes (odds ratio, 7.30; 95% CI, 1.80 to 29.41). CONCLUSIONS: In patients with resuscitated cardiac arrest complicating acute myocardial infarction, prompt prehospital management and early revascularization were associated with a 54% survival rate at 6 months. A strategy including adequate prehospital management, early revascularization, and specific care in dedicated intensive care units should be strongly considered in resuscitated patients after cardiac arrest complicating acute myocardial infarction. PMID- 17353441 TI - Prognostic value of cardiac magnetic resonance stress tests: adenosine stress perfusion and dobutamine stress wall motion imaging. AB - BACKGROUND: Adenosine stress magnetic resonance perfusion (MRP) and dobutamine stress magnetic resonance (DSMR) wall motion analyses are highly accurate for the detection of myocardial ischemia. However, knowledge about the prognostic value of stress MR examinations is limited. We sought to determine the value of MRP and DSMR, as assessed during a single-session examination, in predicting the outcome of patients with known or suspected coronary artery disease. METHODS AND RESULTS: In 513 patients (with known or suspected coronary disease, prior coronary artery bypass graft, or percutaneous coronary intervention), a combined single-session magnetic resonance stress examination (MRP and DSMR) was performed at 1.5 T. For first-pass perfusion imaging, the standard adenosine stress imaging protocol (140 microg x kg(-1) x min(-1) for 6 minutes, 3-slice turbo field echo-echo-planar imaging or steady-state free precession sequence, 0.05 mmol/kg Gd-DTPA) was applied, and for DSMR, the standard high-dose dobutamine/atropine protocol (steady-state free-precession cine sequence) was applied. Stress testing was classified as pathological if at MRP > or = 1 segment showed an inducible perfusion deficit > 25% transmurality or if at DSMR > or = 1 segment showed an inducible wall motion abnormality. During a median follow-up of 2.3 years (range, 0.06 to 4.55 years), 19 cardiac events occurred (4.1%; 9 cardiac deaths, 10 nonfatal myocardial infarctions). The 3-year event-free survival was 99.2% for patients with normal MRP and DSMR and 83.5% for those with abnormal MRP and DSMR. Univariate analysis showed ischemia identified by MRP and DSMR to be predictive of cardiac events (hazard ratio, 12.51; 95% confidence interval, 3.64 to 43.03; and hazard ratio, 5.42; 95% confidence interval, 2.18 to 13.50; P<0.001, respectively); other predictors were diabetes mellitus, known coronary artery disease, and the presence of resting wall motion abnormality. By multivariate analysis, ischemia on magnetic resonance stress testing (MRP or DSMR) was an independent predictor of cardiac events. In a stepwise multivariate model (Cox regression), an abnormal magnetic resonance stress test result had significant incremental value over clinical risk factors and resting wall motion abnormality (P<0.001). CONCLUSIONS: In patients with known or suspected coronary artery disease, myocardial ischemia detected by MRP and DSMR can be used to identify patients at high risk for subsequent cardiac death or nonfatal myocardial infarction. For patients with normal MRP and DSMR, the 3-year event-free survival was 99.2%. MR stress testing provides important incremental information over clinical risk factors and resting wall motion abnormalities. PMID- 17353443 TI - BIPHASIC Trial: a randomized comparison of fixed lower versus escalating higher energy levels for defibrillation in out-of-hospital cardiac arrest. AB - BACKGROUND: There is little clear evidence as to the optimal energy levels for initial and subsequent shocks in biphasic waveform defibrillation. The present study compared fixed lower- and escalating higher-energy regimens for out-of hospital cardiac arrest. METHODS AND RESULTS: The Randomized Controlled Trial to Compare Fixed Versus Escalating Energy Regimens for Biphasic Waveform Defibrillation (BIPHASIC Trial) was a multicenter, randomized controlled trial of 221 out-of-hospital cardiac arrest patients who received > or = 1 shock given by biphasic automated external defibrillator devices that were randomly programmed to provide, blindly, fixed lower-energy (150-150-150 J) or escalating higher energy (200-300-360 J) regimens. Patient mean age was 66.0 years; 79.6% were male. The cardiac arrest was witnessed in 63.8%; a bystander performed cardiopulmonary resuscitation in 23.5%; and initial rhythm was ventricular fibrillation/ventricular tachycardia in 92.3%. The fixed lower- and escalating higher-energy regimen cases were similar for the 106 multishock patients and for all 221 patients. In the primary analysis in multishock patients, conversion rates differed significantly (fixed lower, 24.7%, versus escalating higher, 36.6%; P=0.035; absolute difference, 11.9%; 95% CI, 1.2 to 24.4). Ventricular fibrillation termination rates also were significantly different between groups (71.2% versus 82.5%; P=0.027; absolute difference, 11.3%; 95% CI, 1.6 to 20.9). For the secondary analysis of first shock success, conversion rates were similar between the fixed lower and escalating higher study groups (38.4% versus 36.7%; P=0.92), as were ventricular fibrillation termination rates (86.8% versus 88.8%; P=0.81). There were no distinguishable differences between regimens for survival outcomes or adverse effects. CONCLUSIONS: This is the first randomized trial to compare fixed lower and escalating higher biphasic energy regimens in out-of hospital cardiac arrest, and it demonstrated higher rates of ventricular fibrillation conversion and termination with an escalating higher-energy regimen for patients requiring multiple shocks. These results suggest that patients in ventricular fibrillation benefit from higher biphasic energy levels if multiple defibrillation shocks are required. PMID- 17353442 TI - Oxygen activates the Rho/Rho-kinase pathway and induces RhoB and ROCK-1 expression in human and rabbit ductus arteriosus by increasing mitochondria derived reactive oxygen species: a newly recognized mechanism for sustaining ductal constriction. AB - BACKGROUND: Constriction of the ductus arteriosus (DA) is initiated at birth by inhibition of O2-sensitive K+ channels in DA smooth muscle cells. Subsequent membrane depolarization and calcium influx through L-type calcium channels initiates functional closure. We hypothesize that Rho-kinase activation is an additional mechanism that sustains DA constriction. METHODS AND RESULTS: The effect of increased PO2 on the activity and expression of Rho-kinase was assessed in DAs from neonates with hypoplastic left-heart syndrome (n=15) and rabbits (339 term and 99 preterm rabbits). Rho-kinase inhibitors (Y-27632 and fasudil) prevent and reverse O2 constriction. Heterogeneity exists in the sensitivity of constrictors (PO2=endothelin=phenylephrine>KCl) and of fetal vessels (DA=pulmonary artery>aorta) to Rho-kinase inhibition. Inhibition of L-type calcium channels (nifedipine) or removal of extracellular calcium inhibits approximately two thirds of O2 constriction. Residual DA constriction reflects calcium sensitization, which persists after removal of extracellular calcium and blocking of sarcoplasmic reticulum Ca2+-ATPase. In term DA, an increase in PO2 activates Rho-kinase and thereby increases RhoB and ROCK-1 expression. Activation of Rho-kinase in DA smooth muscle cells is initiated by a PO2-dependent, rotenone sensitive increase in mitochondrion-derived reactive O2 species. O2 effects on Rho-kinase are mimicked by exogenous H2O2. In preterm DAs, immaturity of mitochondrial reactive oxygen species generation is associated with reduced and delayed O2 constriction and lack of PO2-dependent upregulation of Rho-kinase expression. CONCLUSIONS: O2 activates Rho-kinase and increases Rho-kinase expression in term DA smooth muscle cells by a redox-regulated, positive-feedback mechanism that promotes sustained vasoconstriction. Conversely, Rho-kinase inhibitors may be useful in maintaining DA patency, as a bridge to congenital heart surgery. PMID- 17353444 TI - Implications of cardiac risk and low-density lipoprotein cholesterol distributions in the United States for the diagnosis and treatment of dyslipidemia: data from National Health and Nutrition Examination Survey 1999 to 2002. AB - BACKGROUND: Updated guidelines from the National Cholesterol Education Program Adult Treatment Panel III stratify patients into 5 groups of coronary heart disease (CHD) risk that determine intensity of lipid-lowering therapy. The present study assesses the distribution of low-density lipoprotein cholesterol (LDL-C) in the United States across the 5 groups of CHD risk as defined in the updated guidelines. METHODS AND RESULTS: Subjects included 7399 individuals 20 to 79 years of age in the 1999 to 2002 National Health and Nutrition Examination Survey representing 171 million individuals in the United States. CHD risk, LDL-C levels, and goal achievement were determined per Adult Treatment Panel III guidelines. CHD risk assessment incorporated a medical condition review, risk factor summation, and Framingham Risk Score calculation. Percentages were weighted to represent population estimates, and SEs were adjusted for the survey design. The distribution of individuals by CHD risk included 61.1% at lower risk, 10.6% at high risk, and 5.7% at very high risk. From Adult Treatment Panel III criteria, only 5.4% of the population was at "intermediate" risk. Two thirds (66.3%) met their Adult Treatment Panel III-defined LDL-C goal. Of those at high and very high risk, 23% and 26%, respectively, met the goal of LDL-C <100 mg/dL, whereas only 3.1% and 4.6% had an LDL-C <70 mg/dL (or non-high-density lipoprotein C <100 mg/dL). CONCLUSIONS: Most adult US residents are at lower 10 year CHD risk and meet risk-adjusted LDL-C goals. However, large portions of the high-risk population are undertreated. The commonly described population at intermediate risk is small. A novel method of identifying patients who might benefit from additional testing to determine their treatment strategy is provided. PMID- 17353445 TI - Tumor necrosis factor-alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state. AB - BACKGROUND: Pressure overload is accompanied by cardiac myocyte apoptosis, hypertrophy, and inflammatory/fibrogenic responses that lead to ventricular remodeling and heart failure. Despite incomplete understanding of how this process is regulated, the upregulation of tumor necrosis factor (TNF)-alpha after aortic banding in the myocardium is known. In the present study, we tested our hypothesis that TNF-alpha regulates the cardiac inflammatory response, extracellular matrix homeostasis, and ventricular hypertrophy in response to mechanical overload and contributes to ventricular dysfunction. METHODS AND RESULTS: C57/BL wild-type mice and TNF-knockout (TNF-/-) mice underwent descending aortic banding or sham operation. Compared with sham-operated mice, wild-type mice with aortic banding showed a significant increase in cardiac TNF alpha levels, which coincided with myocyte apoptosis, inflammatory response, and cardiac hypertrophy in week 2 and a significant elevation in matrix metalloproteinase-9 activity and impaired cardiac function in weeks 2 and 6. Compared with wild-type mice with aortic banding, TNF-/- mice with aortic banding showed attenuated cardiac apoptosis, hypertrophy, inflammatory response, and reparative fibrosis. These mice also showed reduced cardiac matrix metalloproteinase-9 activity and improved cardiac function. CONCLUSIONS: Findings from the present study have suggested that TNF-alpha contributes to adverse left ventricular remodeling during pressure overload through regulation of cardiac repair and remodeling, leading to ventricular dysfunction. PMID- 17353446 TI - Factors associated with mortality and reoperation in 377 children with total anomalous pulmonary venous connection. AB - BACKGROUND: We sought to determine era-specific changes in the incidence of mortality and reoperation in children with total anomalous pulmonary venous connection. METHODS AND RESULTS: We reviewed the records of 377 children presenting from 1946 to 2005 with total anomalous pulmonary venous connection. Multivariable parametric regression models determined the incidence and risk factors for death and reoperation after repair. Pulmonary venous connection was supracardiac in 44%, infracardiac in 26%, cardiac in 21%, and mixed in 9%. Pulmonary venous obstruction was present in 48% at presentation, most frequently with infracardiac connection type (P<0.001). In total, 327 patients were repaired (median age, 1.7 months). Overall survival from repair was 65+/-6% at 14 years, with a current survival of 97%. Significant (P<0.01) incremental risk factors for postrepair death were cardiac connection type, earlier operation year, younger age at repair, use of epinephrine postoperatively, and postoperative pulmonary venous obstruction. More recent operation year was associated with younger age at repair (P<0.001), decreased use of deep hypothermic circulatory arrest (P<0.001), and use of specific drugs postoperatively (P<0.001). Risk-adjusted estimated 1 year survival for a patient repaired at birth with unfavorable morphology in 2005 is 37% (95% CI, 8 to 80) compared with 96% (95% CI, 91 to 99) for a patient with favorable morphology repaired at 1 year of age. Freedom from reoperation was 82+/ 6% at 11 years after repair, with increased risk associated with mixed connection type (P=0.04) and postoperative pulmonary venous obstruction (P<0.001). CONCLUSIONS: Mortality after total anomalous pulmonary venous connection repair has decreased but remains highest in young patients and in those with cardiac connection type or pulmonary venous obstruction. Unfavorable anatomic characteristics remain important determinants of postrepair survival despite improved perioperative care. PMID- 17353447 TI - Comparison of clinical and administrative data sources for hospital coronary artery bypass graft surgery report cards. AB - BACKGROUND: Regardless of statistical methodology, public performance report cards must use the highest-quality validated data, preferably from a prospectively maintained clinical database. Using logistic regression and hierarchical models, we compared hospital cardiac surgery profiling results based on clinical data with those derived from contemporaneous administrative data. METHODS AND RESULTS: Fiscal year 2003 isolated coronary artery bypass grafting surgery results based on an audited and validated Massachusetts clinical registry were compared with those derived from a contemporaneous state administrative database, the latter using the inclusion/exclusion criteria and risk model of the Agency for Healthcare Research and Quality. There was a 27.4% disparity in isolated coronary artery bypass grafting surgery volume (4440 clinical, 5657 administrative), a 0.83% difference in observed in-hospital mortality (2.05% versus 2.88%), corresponding differences in risk-adjusted mortality calculated by various statistical methodologies, and 1 hospital classified as an outlier only with the administrative data-based approach. The discrepancies in volumes and risk-adjusted mortality were most notable for higher-volume programs that presumably perform a higher proportion of combined procedures that were misclassified as isolated coronary artery bypass grafting surgery in the administrative cohort. Subsequent analyses of a patient cohort common to both databases revealed the smoothing effect of hierarchical models, a 9% relative difference in mortality (2.21% versus 2.03%) resulting from nonstandardized mortality end points, and 1 hospital classified as an outlier using logistic regression but not using hierarchical regression. CONCLUSIONS: Cardiac surgery report cards using administrative data are problematic compared with those derived from audited and validated clinical data, primarily because of case misclassification and nonstandardized end points. PMID- 17353448 TI - Positive pretransplantation cytomegalovirus serology is a risk factor for cardiac allograft vasculopathy in children. AB - BACKGROUND: Cytomegalovirus (CMV) infection has been implicated as a cause of posttransplantation coronary artery disease in adults. The purpose of this retrospective observational study was to evaluate the effect of CMV on outcome after heart transplantation in children. METHODS AND RESULTS: Risk factors tested were recipient age, sex, and pretransplantation CMV serology; use of anti-CMV prophylaxis; posttransplantation evidence of CMV infection; and donor CMV serology. Transplantations were stratified traditionally according to CMV risk as low risk (recipient negative/donor negative), intermediate risk (recipient positive), and high risk (recipient negative/donor positive). Primary outcome measures were (1) development of coronary artery vasculopathy, (2) mortality (or graft loss) that occurred outside the early postoperative period, and (3) death (or graft loss) due to vasculopathy. Analysis was by proportional hazards modeling. A total of 165 children underwent heart transplantation, with a mean age at transplantation of 7.8 (SD 5.6) years. Thirty-two children had laboratory evidence of CMV infection after transplantation, but only 6 developed CMV disease or syndrome. Traditional CMV risk stratification correlated well with CMV infection but did not predict mortality, coronary artery disease, or coronary death. In contrast, positive recipient CMV was the only independent predictor of all 3 outcome measures: coronary artery disease (hazard ratio=3.6), all-cause mortality (partial hazard ratio=4.1), and coronary death (hazard ratio=4.6). CONCLUSIONS: In children, pretransplantation recipient CMV status is a more powerful predictor for the development of clinically significant vasculopathy and subsequent death than traditional risk stratification. This phenomenon warrants further investigation. PMID- 17353449 TI - Images in cardiovascular medicine. Huge pericardial hemangioma imaging. PMID- 17353450 TI - Images in cardiovascular medicine. Cardiovocal syndrome associated with huge left atrium. PMID- 17353451 TI - Images in cardiovascular medicine. Infarction-like electrocardiographic changes due to a myocardial metastasis from a primary lung cancer. PMID- 17353452 TI - Letter by Pischon et al regarding article, "Adiponectin and coronary heart disease: a prospective study and meta-analysis". PMID- 17353453 TI - Spotlight: Michal Tendera, MD, FESC. PMID- 17353454 TI - Aging and sinoatrial node dysfunction: musings on the not-so-funny side. PMID- 17353455 TI - Therapeutic gene regulation: targeting transcription. PMID- 17353456 TI - Endothelial function and dysfunction: testing and clinical relevance. PMID- 17353457 TI - Coronary artery anomalies: an entity in search of an identity. AB - Coronary artery anomalies (CAAs) are a diverse group of congenital disorders whose manifestations and pathophysiological mechanisms are highly variable. The subject of CAAs is undergoing profound evolutionary changes related to the definition, morphogenesis, clinical presentation, diagnostic workup, prognosis, and treatment of these anomalies. To understand the clinical impact of CAAs, the fundamental challenge is the firm establishment, for a particular type of CAA, of a mechanism capable of interference with the coronary artery's function, which is to provide adequate blood flow to the dependent myocardium. The present review focuses on anomalous origination of a coronary artery from the opposite sinus- the subgroup of CAAs that has the most potential for clinical repercussions, specifically sudden death in the young. For this subgroup, solid diagnostic screening protocols should be established, especially for athletes and other young individuals subjected to extreme exertion. Intravascular ultrasonography is the preferred means to evaluate the mechanisms responsible for ischemia in anomalous origination of a coronary artery from the opposite sinus and other potentially significant CAAs. Patients symptomatic of anomalous origination of a coronary artery from the opposite sinus may undergo medical treatment/observation, coronary angioplasty with stent deployment, or surgical repair. To be competent to advise CAA carriers, especially in the context of sporting or military activities, cardiologists should undergo specific training in these disorders. Only multicenter collaboration on protocols dedicated to CAAs can give rise to the large-scale studies needed to define the prognosis and optimal treatment of these disorders. PMID- 17353458 TI - Relating movement control at 9 upper extremity segments to loss of hand function in people with chronic hemiparesis. AB - BACKGROUND AND OBJECTIVE: Loss of hand function in people with hemiparesis is a major contributor to disability poststroke. To use the hand for functional activities, a person may need control of the more proximal upper extremity segments to position and orient the hand with respect to the environment and may need control of the fingers to manipulate objects within the environment. The purpose of this project was to investigate how movement control at proximal, middle, and distal upper extremity segments contributed to loss of hand function in people with chronic hemiparesis. METHODS: 32 patients with hemiparesis (avg 21.4 months postlesion) were studied making isolated movements of shoulder flexion, elbow flexion, forearm pronation/supination, wrist flexion/extension, and individual finger flexion using 3D kinematic techniques. For each segment, 3 variables were obtained: how far a segment could move (active range of motion [AROM]), how well a segment could move by itself (individuation index), and how well a segment could remain still when it was not supposed to move (stationary index). Hand function was measured with a battery of clinical tests, and principal components analysis was used to create a single hand function score for each patient from the test battery. Correlation and regression analyses were used to examine relationships between segmental movement control and hand function. RESULTS: Movement control at all 9 segments of the upper extremity was related to hand function. Of the 9 segments, the thumb tended to have the weakest relationship with hand function. Of the 3 measures of movement control, AROM had strong relationships with and predicted the most variance in hand function (73%). Most of this variance was shared across segments, such that, for AROM, there were no unique contributions provided by proximal, middle, or distal segments. CONCLUSIONS: These data support the idea that loss of movement control covaries across segments and that loss of hand function is due to loss of movement control at all segments, not just at distal ones. PMID- 17353459 TI - Assessment of walking speed and distance in subjects with an incomplete spinal cord injury. AB - BACKGROUND: The 10-meter walk test and 6-minute walk test are increasingly used to evaluate the recovery of walking in patients with incomplete spinal cord injury. So far, there is no evidence whether the application of different walking distances provides complementary information about ambulatory capacity in patients with incomplete spinal cord injury. Studies about testing preferred and maximum speeds in subjects with incomplete spinal cord injury are lacking. OBJECTIVE: To determine whether the combined testing of short and long distances as well as preferred and maximum speeds provides additional information about walking capacity in subjects with incomplete spinal cord injury. METHODS: Depending on the objective, the subjects with incomplete spinal cord injury and age-matched control subjects had to perform the 10-meter walk test or 6-minute walk test at preferred and/or maximum walking speed. RESULTS: During recovery, the preferred walking speed increased but did not differ when assessed during short or long distances in 51 subjects with incomplete spinal cord injury at 1, 3, and 6 months after injury (mean and SD, 6-minute walk test: 0.37 +/- 0.52, 0.87 +/- 0.56, and 1.14 +/- 0.52 ms( -1); 10-meter walk test: 0.40 +/- 0.53, 0.88 +/- 0.51, and 1.12 +/- 0.51 ms(-1), respectively). In 18 subjects with incomplete spinal cord injury, both preferred and maximum walking speeds assessed with the 10-meter walk test predicted the walking speeds of the 6-minute walk test well. Subjects with incomplete spinal cord injury prefer to walk closer to their maximum walking speed (74% +/- 10%) compared to control subjects (59% +/- 8%). CONCLUSIONS: The velocity used for the 6-minute walking distance and the 10-meter walking speed provides comparable information in patients with incomplete spinal cord injury who can perform both tests. However, tests of the preferred and maximum walking speed add information about walking capacity. Due to the easier applicability of the 10-meter walk test in the clinical setting, the authors suggest performing this test at the preferred and maximum speeds for the assessment of walking capacity by 1 month after incomplete spinal cord injury. PMID- 17353460 TI - Use-dependent up- and down-regulation of sensorimotor brain circuits in stroke patients. AB - OBJECTIVE: To examine whether cerebral activity during passive movements decreases with time after stroke, and if reduced activity in the representation for the upper extremity can be reversed with training. METHODS: Brain activity was measured by functional magnetic resonance imaging (fMRI) during passive wrist flexion-extension in 7 patients at varying time points after stroke, in a cross sectional design. Upper limb function was also measured in all patients. Five of the patients took part in a training program and were measured again, behaviorally and with fMRI posttraining. Healthy control individuals of comparable age were also studied. RESULTS: In patients, reduced activity over time after stroke was found for the group in the supplementary motor area (SMA), contralateral primary motor cortex, and prefrontal and parietal association areas along with ipsilateral cerebellum. Activity in most of these areas was also reduced in the patient group as compared to the control group. After a half-hour of daily training for 4 weeks with repetitive passive and active arm movements, cerebral activation increased in the pre-SMA and SMA, ipsilateral primary sensory cortex and intraparietal sulcus, and contralateral cerebellum in parallel with functional improvements of the upper limb. Areas common to both analyses included the SMA, pre-SMA, primary sensory cortex, intraparietal sulcus, and cerebellum. CONCLUSIONS: Our findings suggest that a down-regulation of sensorimotor activity occurs progressively over time as a result of inactivity and that training may reverse the reduced brain activity. PMID- 17353461 TI - Plasticity of spinal centers in spinal cord injury patients: new concepts for gait evaluation and training. AB - Recent data on spinal cord plasticity after spinal cord injury (SCI) were reviewed to analyze the influence of training on the neurophysiological organization of locomotor spinal circuits in SCI patients. In particular, the authors studied the relationship between central pattern generators (CPGs) and motor neuron pool activation during gait. An analysis of the relations between locomotor recovery and compensatory mechanisms focuses on the hierarchical organization of gait parameters and allows characterizing kinematic parameters that are highly stable during different gait conditions and in recovered gait after SCI. The importance of training characteristics and the use of robotic/automated devices in gait recovery is analyzed and discussed. The role of CPG in defining kinematic gait parameters is summarized, and spatio-temporal maps of EMG activity during gait are used to clarify the role of CPG plasticity in sustaining gait recovery. PMID- 17353462 TI - The relationship between balance, disability, and recovery after stroke: predictive validity of the Brunel Balance Assessment. AB - OBJECTIVE: To examine the influence of balance disability on function and the recovery of function after stroke and consequently to assess the predictive validity of the Brunel Balance Assessment (BBA). METHODS: Cross-sectional study of 102 patients admitted consecutively to 6 National Health Service hospitals with weakness 2 to 4 weeks after their first anterior circulation stroke; 75 of whom completed follow-up assessment at 3 months. The BBA was assessed during admission and compared to the Barthel Index and Rivermead Mobility Index at 3 months. RESULTS: Balance disability was the strongest predictor of function (in terms of activities of daily living [ADLs] and mobility disability) in the acute stages. Weakness was also an independent predictor. Recovery of ADLs was independently predicted by balance disability, weakness, age, and premorbid disability, whereas recovery of mobility disability was predicted by balance and age alone. At 3 months, a minority of people with limited sitting balance (0% 22%) and standing balance (25%-50%) recovered independent functional mobility. Most people who could walk initially recovered independent functional mobility (66%-84%), but 16% suffered a decline in their mobility and 44% had enduring limitations in everyday mobility activities. CONCLUSION: Initial balance disability is a strong predictor of function and recovery after stroke. These results demonstrate the predictive validity of the BBA. PMID- 17353463 TI - The test-retest reliability of 2 mobility performance tests in patients with chronic stroke. AB - OBJECTIVE: This study examined test-retest agreement and measurement errors for the Rivermead Mobility Index (RMI) and the Mobility subscale of the Stroke Rehabilitation Assessment of Movement (M-STREAM) in patients with chronic stroke and mild to moderate disability. The authors aimed to determine the level of agreement between test and retest as well as the extent to which a mobility score varies on test-retest measurements. METHODS: Both mobility measures were tested on 50 chronic stroke patients twice, 7 days apart. Intraclass correlation coefficient (ICC(2,1)), a relative reliability index, was used to examine the level of agreement between test and retest. Absolute reliability indices, including the standard error of measurement and the smallest real differences, were used to determine the extent to which the mobility scores varied due to chance variation in measurement. RESULTS: Test-retest agreements were excellent for both mobility measures. The standard errors of measurement of the RMI and the M-STREAM, representing the smallest change threshold that indicates a real improvement (beyond measurement error) for a group of individuals, were 0.8 and 1.5, respectively. The smallest real differences of the RMI and the M-STREAM, exhibiting the smallest change threshold that indicates a real improvement for a single individual, were 2.2 and 4.2, respectively. CONCLUSION: The RMI and the M STREAM have high agreement between the test-retest measurements with acceptable measurement errors due to variation in measurement. The 2 measures can be used by clinicians and researchers to assess the mobility performance and monitor changes over time in stroke patients. PMID- 17353464 TI - Coma reversal after basilar artery thrombolysis. PMID- 17353466 TI - IVIG in myasthenia gravis: getting enough "bang for the buck". PMID- 17353467 TI - Intracranial posterior circulation stenting: promise but still without evidence. PMID- 17353468 TI - Wernicke encephalopathy after obesity surgery: a systematic review. AB - OBJECTIVE: To characterize the clinical features, risk factors, radiographic findings, and prognosis of Wernicke encephalopathy after bariatric surgery. METHODS: We performed a systematic review of MEDLINE, Embase, Ovid, ISI (Science Citation Index), and Google Scholar for case reports, case series, or cohort studies of Wernicke encephalopathy after bariatric surgery. RESULTS: We found 32 cases (27 of whom were women) reported, from 2 weeks to 18 months after the procedure. Most patients had vomiting as a risk factor (n = 25) and presented with the triad of Wernicke encephalopathy (confusion, ataxia, and nystagmus; n = 21). Optic neuropathy, papilledema, deafness, seizures, asterixis, weakness, and sensory and motor neuropathy were also reported. Characteristic radiographic findings were hyperintense signals in the periaqueductal gray area and dorsal medial nucleus of the thalamus; radiographs were normal in 15 patients. One series from Brazil reported 4 patients (among 50 patients) with Wernicke encephalopathy; all presented with vomiting and concomitant peripheral neuropathy at a median of 2.5 months (1.5 to 3 months) after bariatric surgery. Another series identified 2 of 23 patients (both women) with Wernicke encephalopathy after bariatric surgery. CONCLUSION: Wernicke encephalopathy after bariatric surgery usually occurs between 4 and 12 weeks postoperatively, especially in young women with vomiting. Atypical neurologic features are common. The diagnosis is mainly clinical, because radiographic findings are normal in some patients. Prospective studies to determine the prevalence of this problem and protocols for preventive thiamine supplementation need evaluation. PMID- 17353469 TI - DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. AB - For more than a decade, researchers have refined criteria for the diagnosis of dementia with Lewy bodies (DLB) and at the same time have recognized that cognitive impairment and dementia occur commonly in patients with Parkinson disease (PD). This article addresses the relationship between DLB, PD, and PD with dementia (PDD). The authors agreed to endorse "Lewy body disorders" as the umbrella term for PD, PDD, and DLB, to promote the continued practical use of these three clinical terms, and to encourage efforts at drug discovery that target the mechanisms of neurodegeneration shared by these disorders of alpha synuclein metabolism. We concluded that the differing temporal sequence of symptoms and clinical features of PDD and DLB justify distinguishing these disorders. However, a single Lewy body disorder model was deemed more useful for studying disease pathogenesis because abnormal neuronal alpha-synuclein inclusions are the defining pathologic process common to both PDD and DLB. There was consensus that improved understanding of the pathobiology of alpha-synuclein should be a major focus of efforts to develop new disease-modifying therapies for these disorders. The group agreed on four important priorities: 1) continued communication between experts who specialize in PDD or DLB; 2) initiation of prospective validation studies with autopsy confirmation of DLB and PDD; 3) development of practical biomarkers for alpha-synuclein pathologies; 4) accelerated efforts to find more effective treatments for these diseases. PMID- 17353470 TI - Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease. AB - OBJECTIVE: To evaluate the utility of MRI hippocampal and entorhinal cortex atrophy in predicting conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). METHODS: Baseline brain MRI was performed in 139 patients with MCI, broadly defined, and 63 healthy controls followed for an average of 5 years (range 1 to 9 years). RESULTS: Hippocampal and entorhinal cortex volumes were each largest in controls, intermediate in MCI nonconverters, and smallest in MCI converters to AD (37 of 139 patients converted to AD). In separate Cox proportional hazards models, covarying for intracranial volume, smaller hippocampal volume (risk ratio [RR] 3.62, 95% CI 1.93 to 6.80, p < 0.0001), and entorhinal cortex volume (RR 2.43, 95% CI 1.56 to 3.79, p < 0.0001) each predicted time to conversion to AD. Similar results were obtained for hippocampal and entorhinal cortex volume in patients with MCI with Mini-Mental State Examination (MMSE) scores > or = 27 out of 30 (21% converted to AD) and in the subset of patients with amnestic MCI (35% converted to AD). In the total patient sample, when both hippocampal and entorhinal volume were entered into an age stratified Cox model with sex, MMSE, education, and intracranial volume, smaller hippocampal volume (RR 2.21, 95% CI 1.14 to 4.29, p < 0.02) and entorhinal cortex volume (RR 2.48, 95% CI 1.54 to 3.97, p < 0.0002) predicted time to conversion to AD. Similar results were obtained in a Cox model that also included Selective Reminding Test (SRT) delayed recall and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol as predictors. Based on logistic regression models in the 3 year follow-up sample, for a fixed specificity of 80%, the sensitivities for MCI conversion to AD were as follows: age 43.3%, MMSE 43.3%, age + MMSE 63.7%, age + MMSE + SRT delayed recall + WAIS-R Digit Symbol 80.6% (79.6% correctly classified), hippocampus + entorhinal cortex 66.7%, age + MMSE + hippocampus + entorhinal cortex 76.7% (85% correctly classified), age + MMSE + SRT delayed recall + WAIS-R Digit Symbol + hippocampus + entorhinal cortex 83.3% (86.8% correctly classified). CONCLUSIONS: Smaller hippocampal and entorhinal cortex volumes each contribute to the prediction of conversion to Alzheimer disease. Age and cognitive variables also contribute to prediction, and the added value of hippocampal and entorhinal cortex volumes is small. Nonetheless, combining these MRI volumes with age and cognitive measures leads to high levels of predictive accuracy that may have potential clinical application. PMID- 17353471 TI - IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial. AB - OBJECTIVE: We aimed to determine the effectiveness of IV immunoglobulin (IVIG) in the treatment of patients with myasthenia gravis (MG) and worsening weakness in a randomized, placebo-controlled, masked study. METHODS: Fifty-one patients with worsening weakness due to MG were randomized to infusion with 2 g/kg of IVIG or an equivalent volume of IV dextrose 5% in water. The Quantitative Myasthenia Gravis (QMG) Score for Disease Severity, a validated clinical composite scale, was calculated by a masked observer at baseline and days 14 and 28. RESULTS: In IVIG-treated patients, a clinically meaningful improvement in QMG Score for Disease Severity was observed at day 14 and persisted at day 28. The greatest improvement occurred in patients with more severe disease as defined by a QMG Score for Disease Severity greater than 10.5. CONCLUSION: This study provides level 1 evidence for the effectiveness of IV immunoglobulin in patients with worsening weakness due to myasthenia gravis. PMID- 17353472 TI - Sex as a predictor of outcomes in patients treated with thrombolysis for acute stroke. AB - OBJECTIVE: To determine the association between sex and functional outcomes after thrombolytic treatment for acute ischemic stroke in the context of a clinical trial. METHODS: We analyzed predictors of outcome among patients treated with recombinant tissue plasminogen activator (rtPA) in the Glycine Antagonist in Neuroprotection for Patients with Acute Stroke Americas trial, a multicenter, randomized, double-blind, placebo-controlled study of a putative neuroprotectant. RESULTS: Among 1,367 trial patients, 333 (24%) were treated with rtPA within 3 hours. The proportion of patients achieving good functional outcomes at 3 months differed by sex (47.5% of men vs 30.3% of women had Barthel Index [BI] > or = 95; 32.2% of men vs 23.4% of women had modified Rankin Score [mRS] < or = 1). NIH Stroke Score was similar by sex. Men were more likely to have good functional outcomes after adjusting for relevant covariates: for BI > or = 95, adjusted odds ratio (OR) 3.28 (1.74 to 6.17); for mRS < or = 1, adjusted OR 2.12 (1.11 to 4.03). Survival was worse among men: adjusted OR 0.45 (0.20 to 1.01). Other predictors of functional outcomes included age, stroke side, severity, complications, and infections. CONCLUSIONS: Among tissue plasminogen activator treated patients in this clinical trial population, men were approximately three times as likely to have good functional outcomes, despite elevated mortality. Thrombolysis for stroke may not reverse the tendency for women to have worse functional outcomes after stroke. PMID- 17353473 TI - CMT1X phenotypes represent loss of GJB1 gene function. AB - OBJECTIVE: To investigate possible genotype-phenotype correlations and to evaluate the natural history of patients with Charcot-Marie-Tooth disease type 1X (CMT1X). BACKGROUND: CMT1X is caused by over 260 distinct mutations in the gap junction beta 1 (GJB1) gene, located on the X chromosome, which encodes the gap junction protein connexin 32 (Cx32). The natural history of CMT1X is poorly understood, and it remains unknown whether particular mutations cause more severe neuropathies through abnormal gain-of-function mechanisms. METHODS: We evaluated 73 male patients with CMT1X, who each have 1 of 28 different GJB1 mutations predicted to affect nearly all domains of Cx32. Disability was evaluated quantitatively by the CMT Neuropathy Score (CMTNS) as well as by the CMT Symptom Score (CMTSS) and the CMT Examination Score (CMTES), which are both based on the CMTNS. Patients were also evaluated by neurophysiology. RESULTS: In all patients, disability increased with age, and the degree of disability was comparable with that observed in patients with a documented GJB1 deletion. Disability correlated with a loss of motor units as assessed by motor unit number estimates. CONCLUSIONS: Taken together, these data suggest that most GJB1 mutations cause neuropathy by a loss of normal connexin 32 function. Therefore, treatment of male patients with Charcot-Marie-Tooth disease type 1X may prove amenable to gene replacement strategies. PMID- 17353474 TI - Long-term outcome of elective stenting for symptomatic intracranial vertebrobasilar stenosis. AB - Seventy-nine consecutive patients with symptomatic atherosclerotic stenosis > or = 50% of intracranial vertebrobasilar artery (VBA) were treated by elective stenting. There were five strokes within 30 days, and three strokes in the VBA territory after 30 days (mean of 812 days). The annual stroke rate in the VBA territory (including any stroke and death within 30 days) was 4.6%. At the last follow-up time, 73 patients were independent (modified Rankin scale grade < or = 2). The outcome compares favorably with medical therapy. PMID- 17353475 TI - Encephalopathy, stroke, and myocardial infarction with DMSO use in stem cell transplantation. AB - Stem cell transplants are established therapy for hematologic and solid tumor malignancies. Known neurological complications of stem cell transplantation include CNS infection, seizures, strokes, metabolic encephalopathy, and hemorrhage. We report two cases of autologous stem cell transplantation complicated by cerebral infarction and myocardial injury. We postulate that the cryopreservative dimethyl sulfoxide may be responsible. PMID- 17353476 TI - Dominant limb motor impersistence associated with callosal disconnection. AB - Motor impersistence occurs more frequently after right than left hemispheric lesions. Following a callosal lesion, motor impersistence may thus occur more frequently in the right (dominant) than left limb. After an infarction involving the right medial frontal lobe and corpus callosum, a 66-year-old right-handed man demonstrated right limb motor impersistence on bedside evaluation, which was substantiated experimentally. Results demonstrated hemispatial effects with greater impersistence in the neglected (right) space. PMID- 17353477 TI - High CSF neurofilament heavy chain levels in neuromyelitis optica. AB - The neurofilament heavy chain (NfHSMI35), a biomarker of axonal damage in the CSF, was measured in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). Significantly high CSF NfHSMI35 levels (>0.73 ng/mL) were found in 6 of 24 (25%) of the patients with NMO but none of the patients with MS (0/24). This finding suggests that axonal damage is more severe in NMO than in MS. PMID- 17353478 TI - Novel prion protein gene mutation presenting with subacute PSP-like syndrome. AB - A 62-year-old Indonesian woman presenting with a progressive supranuclear palsy like syndrome was confirmed post mortem as dying from a spongiform encephalopathy. Despite an illness duration of only 4 months, brain MRI, EEG, and CSF analysis for 14-3-3 proteins all failed to disclose changes typical of Creutzfeldt-Jakob disease. Neuropathologic examination revealed multicentric, prion protein-positive, amyloid plaques as typically seen in Gerstmann-Straussler Scheinker syndrome. Prion protein gene analysis revealed a previously unreported A133V mutation. PMID- 17353479 TI - Progressive multifocal leukoencephalopathy with selective involvement of the pyramidal tracts. PMID- 17353480 TI - Primary spinal intramedullary lymphoma mimicking ependymoma. PMID- 17353481 TI - Women and men are equally disabled by Charcot-Marie-Tooth disease type 1A. PMID- 17353482 TI - Ocular lateropulsion from a brainstem stroke can compensate for hemianopia. PMID- 17353483 TI - Fixed dystonia unresponsive to pallidal stimulation improved by motor cortex stimulation. PMID- 17353484 TI - Volunteering for early phase gene transfer research in Parkinson disease. PMID- 17353485 TI - SSEPs and prognosis in postanoxic coma: only short or also long latency responses? PMID- 17353486 TI - Syncope in migraine: the population-based CAMERA study. PMID- 17353487 TI - Longevity and cardiovascular disease: context and overview. PMID- 17353488 TI - Two-tiered health care: a problematic double standard. PMID- 17353489 TI - Access and ability to pay: the ethics of a tiered health care system. PMID- 17353490 TI - Characteristics of Framingham offspring participants with long-lived parents. AB - BACKGROUND: Prior research has suggested that delay or avoidance of cardiovascular disease and cardiovascular disease risk factors plays an important role in longevity. METHODS: We studied 1697 Framingham Heart Study (FHS) offspring members 30 years or older, whose parents (1) participated in the original FHS cohort and (2) achieved age 85 years or died before January 1, 2005. Offspring participants (mean +/- SD age, 40 +/- 7 years; 51% women) were grouped according to whether neither (n = 705), one (n = 804), or both parents (n = 188) survived to 85 years or older. We examined offspring risk factors at examination cycle 1 (1971-1975) including age, sex, education, cigarette smoking, systolic and diastolic blood pressures, total-high-density lipoprotein cholesterol ratio, body mass index, and Framingham Risk Score. Participants returning for examination cycle 3 (1983-1987; n = 1319) were eligible for inclusion in longitudinal analyses evaluating risk factor progression from baseline to a higher follow-up risk category. RESULTS: For all factors studied, except body mass index, we observed statistically significant linear trends for lower offspring examination 1 risk factor levels with increasing parental survival category. The mean Framingham Risk Score was most favorable in offspring with both parents surviving to 85 years or older and was progressively worse in those with one or no long-lived parent (0.55, 1.08, and 1.71, respectively; P value for trend, <.001). Longitudinally, offspring of parents who lived longer had lower risk of blood pressure and Framingham Risk Score progression. CONCLUSIONS: Our findings suggest that individuals with long-lived parents have advantageous cardiovascular risk profiles in middle age compared with those whose parents died younger. The risk factor advantage persists over time. PMID- 17353491 TI - Behind closed doors: management of patient expectations in primary care practices. AB - BACKGROUND: Managed care restrictions on resource use may affect communication between patients and health care professionals. METHODS: To characterize negotiations between primary care physicians and patients with expectations for new medications, tests, or referrals, this observational study combined survey data with audiotape recordings of clinical encounters. Fifty-five physicians from 20 randomly selected primary care practices in a managed care network and 211 patients who voiced specific expectations in a previsit survey were included. From the recorded clinic visits we determined modes of negotiation of patient expectations and requests. From the surveys we determined patient previsit expectations, postvisit fulfillment of expectations, satisfaction, and trust. RESULTS: Two-hundred fifty-six self-reported expectations were captured in 200 audiotape-recorded encounters. Of the previsit expectations, 97.3% were discussed during the encounter. Expectations were expressed by direct patient request (40.6%), mentioning of symptoms related to request (29.7%), or physician initiated discussion (27.0%). Most expectations were met (66.8%); physicians suggested an alternative 21.6% of the time. Expectations for medications and tests were met more frequently than expectations for referrals (75.6% and 71.4% vs 40.8%). Patient satisfaction and trust remained high regardless of whether expectations were met. Physicians reported that they would not have ordered 62 (44.9%) of 138 requests had the patients not directly asked, and they were uncomfortable filling 8 requests (12.9%). CONCLUSIONS: Previsit expectations for medications, tests, or referrals were discussed at the visit, and physicians met or offered alternatives for nearly 90%. Patients generally received what they asked for and altered physician behavior nearly half of the time. PMID- 17353492 TI - Efficacy of communication skills training for giving bad news and discussing transitions to palliative care. AB - BACKGROUND: Few studies have assessed the efficacy of communication skills training for postgraduate physician trainees at the level of behaviors. We designed a residential communication skills workshop (Oncotalk) for medical oncology fellows. The intervention design built on existing successful models by teaching specific communication tasks linked to the patient's trajectory of illness. This study evaluated the efficacy of Oncotalk in changing observable communication behaviors. METHODS: Oncotalk was a 4-day residential workshop emphasizing skills practice in small groups. This preintervention and postintervention cohort study involved 115 medical oncology fellows from 62 different institutions during a 3-year study. The primary outcomes were observable participant communication skills measured during standardized patient encounters before and after the workshop in giving bad news and discussing transitions to palliative care. The standardized patient encounters were audiorecorded and assessed by blinded coders using a validated coding system. Before-after comparisons were made using each participant as his or her own control. RESULTS: Compared with preworkshop standardized patient encounters, postworkshop encounters showed that participants acquired a mean of 5.4 bad news skills (P<.001) and a mean of 4.4 transitions skills (P<.001). Most changes in individual skills were substantial; for example, in the bad news encounter, 16% of participants used the word "cancer" when giving bad news before the workshop, and 54% used it after the workshop (P<.001). Also in the bad news encounter, blinded coders were able to identify whether a standardized patient encounter occurred before or after the workshop in 91% of the audiorecordings. CONCLUSION: Oncotalk represents a successful teaching model for improving communication skills for postgraduate medical trainees. PMID- 17353493 TI - Toward shared decision making at the end of life in intensive care units: opportunities for improvement. AB - BACKGROUND: In North America, families generally wish to be involved in end-of life decisions when the patient cannot participate, yet little is known about the extent to which shared decision making occurs in intensive care units. METHODS: We audiotaped 51 physician-family conferences about major end-of-life treatment decisions at 4 hospitals from August 1, 2000, to July 31, 2002. We measured shared decision making using a previously validated instrument to assess the following 10 elements: discussing the nature of the decision, describing treatment alternatives, discussing the pros and cons of the choices, discussing uncertainty, assessing family understanding, eliciting patient values and preferences, discussing the family's role in decision making, assessing the need for input from others, exploring the context of the decision, and eliciting the family's opinion about the treatment decision. We used a mixed-effects regression model to determine predictors of shared decision making and to evaluate whether higher levels of shared decision making were associated with greater family satisfaction. RESULTS: Only 2% (1/51) of decisions met all 10 criteria for shared decision making. The most frequently addressed elements were the nature of the decision (100%) and the context of the decision to be made (92%). The least frequently addressed elements were the family's role in decision making (31%) and an assessment of the family's understanding of the decision (25%). In multivariate analysis, lower family educational level was associated with less shared decision making (partial correlation coefficient, 0.34; standardized beta, .3; P = .02). Higher levels of shared decision making were associated with greater family satisfaction with communication (partial correlation coefficient, 0.15; standardized beta, .09; P = .03). CONCLUSIONS: Shared decision making about end-of-life treatment choices was often incomplete, especially among less educated families. Higher levels of shared decision making were associated with greater family satisfaction. Shared decision making may be an important area for quality improvement in intensive care units. PMID- 17353494 TI - Body mass index and risk of suicide among men. AB - BACKGROUND: Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) has been linked to depression and the risk of suicide attempts and deaths in conflicting directions. METHODS: In a prospective cohort study of 46 755 men free of cancer enrolled in the Health Professionals Follow-up Study, participants reported their height, weight, diet, and physical activity on repeated occasions beginning in 1986 and were followed up until death or until February 2002. A subsample of 1829 men reported their mental health-related quality of life with the Mental Component Summary Scale of the 36-Item Short-Form Health Survey in 1998. RESULTS: A total of 131 men died from suicide during follow-up. A higher BMI was related to a graded decline in the suicide mortality rate, from 52 per 100 000 person-years among men with a BMI of less than 21 to 13 per 100 000 among men with a BMI of 30 or higher; the adjusted hazard ratio per 1 U BMI increment was 0.89 (95% confidence interval, 0.84-0.95; P<.001). The relationship was consistent when baseline or updated measures of BMI were used and with adjustment for medical illness, dietary factors, antidepressant use, physical activity, or social support. Height and physical activity were not strongly associated with risk. Analyses of mental health-related quality of life showed a similar positive relationship with BMI. CONCLUSIONS: Among men, risk of death from suicide is strongly inversely related to BMI, but not to height or to physical activity. Although obesity cannot be recommended on the basis of its detrimental effects, further research into the mechanisms of lower risk among overweight and obese men may provide insights into effective methods of suicide prevention. PMID- 17353495 TI - Bringing the war back home: mental health disorders among 103,788 US veterans returning from Iraq and Afghanistan seen at Department of Veterans Affairs facilities. AB - BACKGROUND: Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) have endured high combat stress and are eligible for 2 years of free military service-related health care through the Department of Veterans Affairs (VA) health care system, yet little is known about the burden and clinical circumstances of mental health diagnoses among OEF/OIF veterans seen at VA facilities. METHODS: US veterans separated from OEF/OIF military service and first seen at VA health care facilities between September 30, 2001 (US invasion of Afghanistan), and September 30, 2005, were included. Mental health diagnoses and psychosocial problems were assessed using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The prevalence and clinical circumstances of and subgroups at greatest risk for mental health disorders are described herein. RESULTS: Of 103 788 OEF/OIF veterans seen at VA health care facilities, 25 658 (25%) received mental health diagnosis(es); 56% of whom had 2 or more distinct mental health diagnoses. Overall, 32 010 (31%) received mental health and/or psychosocial diagnoses. Mental health diagnoses were detected soon after the first VA clinic visit (median of 13 days), and most initial mental health diagnoses (60%) were made in nonmental health clinics, mostly primary care settings. The youngest group of OEF/OIF veterans (age, 18-24 years) were at greatest risk for receiving mental health or posttraumatic stress disorder diagnoses compared with veterans 40 years or older. CONCLUSIONS: Co occurring mental health diagnoses and psychosocial problems were detected early and in primary care medical settings in a substantial proportion of OEF/OIF veterans seen at VA facilities. Targeted early detection and intervention beginning in primary care settings are needed to prevent chronic mental illness and disability. PMID- 17353496 TI - N-terminal pro-B-type natriuretic peptide as a diagnostic test for ventricular dysfunction in patients with coronary disease: data from the heart and soul study. AB - BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing is useful for diagnosing acute decompensated heart failure. Whether NT-proBNP can be used to detect ventricular dysfunction in patients with stable coronary heart disease (CHD) and no history of heart failure is unknown. METHODS: We measured NT proBNP levels and performed transthoracic echocardiography in 815 participants from the Heart and Soul Study, who had stable CHD and no history of heart failure. We hypothesized that NT-proBNP concentrations lower than 100 pg/mL would rule out ventricular dysfunction and concentrations higher than 500 pg/mL would identify ventricular dysfunction. We calculated sensitivities, specificities, likelihood ratios, and areas under the receiver operating characteristic curves for NT-proBNP as a case-finding instrument for systolic and diastolic dysfunction. RESULTS: Of the 815 participants with no history of heart failure, 68 (8%) had systolic dysfunction defined as a left ventricular ejection fraction of 50% or lower. Of the 730 participants for whom the presence or absence of diastolic dysfunction could be determined, 78 (11%) had diastolic dysfunction defined as a pseudonormal or restrictive filling pattern. The overall area under the receiver operating characteristic curve for detecting systolic or diastolic dysfunction was 0.78 (95% confidence interval, 0.74-0.82). Likelihood ratios were 0.28 for NT-proBNP concentrations lower than 100 pg/mL, 0.95 for concentrations between 100 and 500 pg/mL, and 4.1 for concentrations higher than 500 pg/mL. A test result lower than 100 pg/mL reduced the probability of ventricular dysfunction from a pretest probability of 18% to a posttest probability of 6%. A test result higher than 500 pg/mL increased the probability of ventricular dysfunction from a pretest probability of 18% to a posttest probability of 47%. A test result between 100 and 500 pg/mL did not change the probability of ventricular dysfunction. CONCLUSION: In patients with stable CHD and no history of heart failure, NT-proBNP levels lower than 100 pg/mL effectively rule out ventricular dysfunction, with a negative likelihood ratio of 0.28. PMID- 17353497 TI - Long-term survival after heart failure: a contemporary population-based perspective. AB - BACKGROUND: Heart failure (HF) is a major public health problem that is associated with substantial morbidity, impaired quality of life, and diminished survival. Despite the considerable prevalence of HF in the United States, there are limited published data describing the contemporary long-term prognosis of patients hospitalized with decompensated HF. METHODS: A total of 2445 residents in the Worcester metropolitan area discharged from 11 greater Worcester hospitals after confirmed acute HF during 2000 comprised the study sample. Follow-up of discharged hospital survivors was carried out through 2005. RESULTS: The mean age of the study population was 76 years, 43.4% were men, and approximately three quarters had been previously diagnosed as having HF. Among discharged hospital patients, 37.3% died during the first year after hospital discharge, while 78.5% died during the 5-year follow-up period. Several subgroups of patients were at significantly increased risk for dying during the first year after hospital discharge. This included older persons (> or =85 years) (adjusted odds ratio [OR], 2.11; 95% confidence interval [CI], 1.35-3.29), patients with a history of chronic obstructive pulmonary disease (OR, 1.39; 95% CI, 1.15-1.69) or HF (OR, 1.26; 95% CI, 1.00-1.59), and patients with elevated serum urea nitrogen levels during hospitalization (OR, 1.02; 95% CI, 1.01-1.03). CONCLUSIONS: The results of our community-wide study demonstrate the poor long-term prognosis of patients surviving hospitalization for decompensated HF. Despite advances in the therapeutic management of these patients, their long-term survival remains guarded. Efforts are needed to improve the long-term survival of patients with this clinical syndrome. PMID- 17353498 TI - No association between the common MTHFR 677C->T polymorphism and venous thrombosis: results from the MEGA study. AB - BACKGROUND: Increased homocysteine levels are related to the occurrence of venous thrombosis, but whether this relation is causal is unclear. The T-variant of the common methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism mildly increases homocysteine levels. Meta-analyses have demonstrated a weak effect of the MTHFR 677TT genotype on risk but are sensitive to selective publication of positive results. The aim of the present study was to evaluate the effect of the MTHFR genotype on the risk of venous thrombosis, overall and in subgroups of known risk factors, in a single large study. METHODS: In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA Study), a population-based case-control study, we collected DNA from 4375 patients with a first deep vein thrombosis of the leg or pulmonary embolism and from 4856 control subjects. Information about risk factors for venous thrombosis was obtained from questionnaires. RESULTS: MTHFR 677C-->T was not associated with the risk of venous thrombosis (odds ratio [95% confidence interval], 0.99 [0.91 1.08] for the CT genotype and 0.94 [0.81-1.08] for the TT genotype). Stratification by known risk factors for venous thrombosis provided no evidence of an association in specific groups. CONCLUSIONS: In a single large study, MTHFR 677C-->T was not associated with the risk of venous thrombosis, and the narrow confidence interval excludes even a small effect. Therefore, mildly elevated homocysteine levels as a result of MTHFR 677TT do not seem to cause venous thrombosis. There is no rationale for measuring the MTHFR 677C-->T variant for clinical purposes. PMID- 17353499 TI - Effect of a high-fiber diet vs a fiber-supplemented diet on C-reactive protein level. AB - BACKGROUND: Diets high in fiber are associated with lower levels of inflammatory markers. This study examined the reduction in inflammation from a diet supplemented with fiber compared with a diet naturally high in fiber. METHODS: Randomized crossover intervention trial of 2 diets, a high-fiber (30-g/d) Dietary Approaches to Stop Hypertension (DASH) diet or fiber-supplemented diet (30 g/d), after a baseline (regular) diet period of 3 weeks. There were 35 participants (18 lean normotensive and 17 obese hypertensive individuals) aged 18 to 49 years. RESULTS: The study included 28 women and 7 men; 16 (46%) were black, the remainder white. The mean (SD) fiber intake on baseline diets was 11.9 (0.3) g/d; on the high-fiber DASH diet, 27.7 (0.6) g/d; and on the supplemented diet, 26.3 (0.4) g/d. Overall, the mean C-reactive protein (CRP) level changed from 4.4 to 3.8 mg/L (-13.7%; P = .046) in the high-fiber DASH diet group and to 3.6 mg/L ( 18.1%) in the fiber-supplemented diet group (P = .03). However, CRP levels decreased in the 18 lean normotensive participants in either intervention diet group (2.0 mg/L [baseline] vs 1.4 mg/L [high-fiber DASH] vs 1.2 mg/L [supplemented]); P<.05) but did not change significantly (7.1 mg/L [baseline] vs 6.2 mg/L [high-fiber DASH] vs 6.5 mg/L [supplemented]; P>.05) in obese hypertensive participants. Neither age nor race influenced the response of CRP levels to the diets. No evidence of a crossover effect was detected. CONCLUSIONS: The results demonstrate that fiber intake of about 30 g/d) from a diet naturally rich in fiber or from a supplement can reduce levels of CRP. Further research is needed to more clearly elucidate the differential effect seen in lean vs obese individuals and whether modification of dietary fiber may be helpful in modulating inflammation and its consequent cardiovascular consequences. PMID- 17353500 TI - Physicians and electronic health records: a statewide survey. AB - BACKGROUND: Electronic health records (EHRs) allow for a variety of functions, ranging from visit documentation to laboratory test ordering, but little is known about physicians' actual use of these functions. METHODS: We surveyed a random sample of 1884 physicians in Massachusetts by mail and assessed availability and use of EHR functions, predictors of use, and the relationships between EHR use and physicians' perceptions of medical practice. RESULTS: A total of 1345 physicians responded to the survey (71.4% response rate), and 387 (28.8%) reported that their practice had adopted EHRs. More than 80% of physicians with EHRs reported having the ability to view laboratory reports (84.8%) and document visits electronically (84.0%), but considerably fewer reported being able to order laboratory tests electronically (46.8%) or transmit prescriptions to a pharmacy electronically (44.7%). Fewer than half of the physicians who had systems with clinical decision support, transmittal of electronic prescriptions, and radiology order entry actually used these functions most or all of the time. Compared with physicians who had not adopted EHRs, EHR users reported more positive views of the effects of computers on health care; there were no significant differences in these attitudes between high and low users of EHRs. Overall, about 1 in 4 physicians reported dissatisfaction with medical practice; there was no difference in this measure by EHR adoption or use. CONCLUSIONS: There is considerable variability in the functions available in EHRs and in the extent to which physicians use them. Future work should emphasize factors that affect the use of available functions. PMID- 17353501 TI - Risedronate for the prevention of hip fractures: concern about validity of trials. PMID- 17353502 TI - Protective effect of diabetes against metastasis in patients with non-small cell lung cancer. PMID- 17353503 TI - Alternatives for menopause. PMID- 17353504 TI - Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. AB - OBJECTIVE: In patients with type 2 diabetes, exenatide reduces A1C, postprandial and fasting glucose, and weight. In this study we investigated the effects of continuous exenatide administration from a long-acting release (LAR) formulation. RESEARCH DESIGN AND METHODS: In this randomized, placebo-controlled phase 2 study, exenatide LAR (0.8 or 2.0 mg) was administered subcutaneously once weekly for 15 weeks to subjects with type 2 diabetes (n = 45) suboptimally controlled with metformin (60%) and/or diet and exercise (40%): 40% female, A1C (mean +/- SD) 8.5 +/- 1.2%, fasting plasma glucose 9.9 +/- 2.3 mmol/l, weight 106 +/- 20 kg, and diabetes duration 5 +/- 4 years. RESULTS: From baseline to week 15, exenatide LAR reduced mean +/- SE A1C by -1.4 +/- 0.3% (0.8 mg) and -1.7 +/- 0.3% (2.0 mg), compared with +0.4 +/- 0.3% with placebo LAR (P < 0.0001 for both). A1C of < or =7% was achieved by 36 and 86% of subjects receiving 0.8 and 2.0 mg exenatide LAR, respectively, compared with 0% of subjects receiving placebo LAR. Fasting plasma glucose was reduced by -2.4 +/- 0.9 mmol/l (0.8 mg) and -2.2 +/- 0.5 mmol/l (2.0 mg) compared with +1.0 +/- 0.7 mmol/l with placebo LAR (P < 0.001 for both). Exenatide LAR reduced self-monitored postprandial hyperglycemia. Subjects receiving 2.0 mg exenatide LAR had body weight reductions (-3.8 +/- 1.4 kg) (P < 0.05), whereas body weight was unchanged with both placebo LAR and the 0.8-mg dose. Mild nausea was the most frequent adverse event. No subjects treated with exenatide LAR withdrew from the study. CONCLUSIONS: Exenatide LAR offers the potential of 24-h glycemic control and weight reduction with a novel once-weekly treatment for type 2 diabetes. PMID- 17353505 TI - Depression among type 2 diabetes rural Appalachian clinic attendees. PMID- 17353506 TI - Toxic human islet amyloid polypeptide (h-IAPP) oligomers are intracellular, and vaccination to induce anti-toxic oligomer antibodies does not prevent h-IAPP induced beta-cell apoptosis in h-IAPP transgenic mice. AB - OBJECTIVE: Islets in type 2 diabetes are characterized by a deficit in beta cells, increased beta-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). The toxic form of amyloidogenic protein oligomers are distinct and smaller than amyloid fibrils and act by disrupting membranes. Using antibodies that bind to toxic IAPP oligomers (but not IAPP monomers or fibrils) and a vaccination-based approach, we sought to establish whether IAPP toxic oligomers form intra- or extracellularly and whether vaccination to induce anti toxic oligomer antibodies prevents IAPP-induced apoptosis in human IAPP (h-IAPP) transgenic mice. RESEARCH DESIGN AND METHODS: Pancreas was sampled from two h IAPP transgenic mouse models and examined by immunohistochemistry for toxic oligomers. The same murine models were vaccinated with toxic oligomers of Alzheimer beta protein (AbetaP(1-40)) and anti-oligomer titers, and blood glucose and islet pathology were monitored. RESULTS: Toxic oligomers were detected intracellularly in approximately 20-40% of h-IAPP transgenic beta-cells. Vaccine induced high titers of anti-h-IAPP toxic oligomers in both transgenic models, but beta-cell apoptosis was, if anything, further increased in vaccinated mice, so that neither loss of beta-cell mass nor diabetes onset was delayed. CONCLUSIONS: IAPP toxic oligomers form in h-IAPP transgenic mouse models, and anti-toxic oligomer antibodies do not prevent h-IAPP-induced beta-cell apoptosis. These data suggest that prevention of h-IAPP oligomer formation may be more useful than a vaccination-based approach in the prevention of type 2 diabetes. PMID- 17353508 TI - Cerebral autoregulation and blood pressure lowering. PMID- 17353510 TI - To dip or not to dip: of arterial pressure physiology, system's analysis, and information. PMID- 17353509 TI - Peroxisome proliferator-activated receptor alpha-independent actions of fenofibrate exacerbates left ventricular dilation and fibrosis in chronic pressure overload. AB - Progressive cardiac remodeling is characterized by subsequent chamber hypertrophy, enlargement, and pump dysfunction. It is also associated with increased cardiac fibrosis and matrix turnover. Interestingly, peroxisome proliferator-activated receptor (PPAR) alpha activators reduce cardiac hypertrophy, inflammation, and fibrosis. Little is known about the role of fenofibrates in mediating PPARalpha-independent effects in response to chronic pressure overload (PO). Wild-type and PPARalpha-deficient mice were subjected to chronic PO caused by ascending aortic constriction to test the role of fenofibrates in chronic, progressive cardiac remodeling by a PPARalpha independent mechanism. Mice were randomized to regular chow or chow-containing fenofibrate (100 mg/kg of body weight per day) for 1 week before and 8 weeks after ascending aortic constriction. In the presence of PPARalpha, wild-type chronic PO mice, treated with fenofibrate, had improved cardiac remodeling. However, PO PPARalpha-deficient mice treated with fenofibrate had increased mortality, significantly adverse left ventricular end diastolic (3.4+/-0.1 versus 4.2+/-0.1 mm) and end systolic (1.5+/-0.2 versus 2.5+/-0.2 mm) dimensions, and fractional shortening (57+/-3% versus 40+/-3%). Fenofibrate also increased myocardial hypertrophy, cardiac fibrosis, and the ratio of matrix metalloproteinase-2/tissue inhibitor of matrix metalloproteinase-2 in PO PPARalpha-deficient mice. Fenofibrate inhibited matrix metalloproteinase activity in vitro and aldosterone-induced increases in extracellular signal-regulated kinase phosphorylation. Thus, fenofibrate improved cardiac remodeling in chronic PO mice. However, in PPARalpha-deficient mice, this chronic PO was exacerbated and associated with increased myocardial fibrosis and altered matrix remodeling. In the absence of PPARalpha, fenofibrates exerts deleterious, pleiotropic myocardial actions. This is an important observation, because PPARalpha agonists are considered possible inhibitory regulators of cardiac remodeling in the remodeled heart. PMID- 17353511 TI - Cerebral hemodynamics after short- and long-term reduction in blood pressure in mild and moderate hypertension. AB - This study tested the hypothesis that acute reduction in blood pressure (BP) at the initial stage of antihypertensive therapy compromises brain perfusion and dynamic cerebral autoregulation in patients with hypertension. Cerebral blood flow velocity and BP were measured in patients with mild and moderate hypertension and in healthy volunteers at baseline upon reduction of BP within 1 to 2 weeks of administration of losartan/hydrochlorothiazide and after 3 to 4 months of treatment. The transfer function between beat-to-beat changes in BP and cerebral blood flow velocity was estimated to assess dynamic autoregulation. After 1 to 2 weeks of treatment, BP was reduced in mild (143+/-7/88+/-4 versus 126+/-12/77+/-6 mm Hg) and moderate hypertension (163+/-11/101+/-9 versus 134+/ 17/84+/-9 mm Hg; P<0.05). These reductions in BP were well maintained over the 3 to 4 month period. Cerebral blood flow velocity did not change, whereas cerebrovascular resistance index was reduced by 17% (P<0.05) after reduction in BP. Responses of cerebral blood flow velocity to head-up tilt remained unchanged. Baseline transfer function gain at the low frequencies (0.07 to 0.20 Hz) was reduced in moderate hypertension, consistent with cerebral vasoconstriction and/or enhanced dynamic autoregulation. However, this reduced transfer function gain was restored to the level of control subjects after reduction in BP. These findings, contrary to our hypothesis, demonstrate that there is a rapid adaptation of the cerebral vasculature to protect the brain from hypoperfusion even at the initial stage of antihypertensive therapy in patients with mild and moderate hypertension. PMID- 17353512 TI - To dip or not to dip: on the physiology of blood pressure decrease during nocturnal sleep in healthy humans. AB - That sleep is accompanied by a blood pressure decrease is well known; however, the underlying physiology deserves further investigation. The present study examines in healthy subjects 2 main questions: is this dipping actively evoked? and what are the consequences of nondipping for daytime blood pressure? Nocturnal blood pressure was extrinsically elevated in 12 sleeping subjects to mean daytime values by continuously infused phenylephrine. This nondipping significantly lowered morning blood pressure during rest and 3 hours after resuming physical activity compared with a control condition (isotonic saline). Neither muscle sympathetic nerve activity nor sensitivity of alpha-adrenoceptors was reduced. However, the set point for initiation of regulatory responses through the baroreflex was clearly shifted toward lower blood pressure levels. Our results support the hypothesis of an actively regulated central mechanism for blood pressure resetting and set point consolidation of the baroreflex during nighttime sleep. This is suggested by the fact that extrinsically induced nondipping induces sustained decrease in blood pressure during the following morning through an actively lowered baroreflex set point. PMID- 17353513 TI - Direct Renin inhibition with aliskiren in obese patients with arterial hypertension. AB - Current guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommend first-line treatment with a thiazide diuretic but do not provide specific guidance for obese patients. The renin system is activated in obesity-associated arterial hypertension. Therefore, we tested the hypothesis that the oral direct renin inhibitor aliskiren could provide additive blood pressure lowering in obese patients with hypertension (body mass index >or=30 kg/m(2); mean sitting diastolic blood pressure: 95 to 109 mm Hg) who had not responded to 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg. After a 2- to 4-week washout, 560 patients received single-blind HCTZ (25 mg) for 4 weeks; 489 nonresponders were randomly assigned to double-blind aliskiren (150 mg), irbesartan (150 mg), amlodipine (5 mg), or placebo for 4 weeks added to HCTZ (25 mg), followed by 8 weeks on double the initial doses of aliskiren, irbesartan, or amlodipine. After 8 weeks of double-blind treatment (4 weeks on the higher dose), aliskiren/HCTZ lowered blood pressure by 15.8/11.9 mm Hg, significantly more (P<0.0001) than placebo/HCTZ (8.6/7.9 mm Hg). Aliskiren/HCTZ provided blood pressure reductions similar to those with irbesartan/HCTZ and amlodipine/HCTZ (15.4/11.3 and 13.6/10.3 mm Hg, respectively), with similar tolerability to placebo/HCTZ. Adverse event rates were highest with amlodipine/HCTZ because of a higher incidence of peripheral edema (11.1% versus 0.8% to 1.6% in other groups). In conclusion, combination treatment with aliskiren is a highly effective and well-tolerated therapeutic option for obese patients with hypertension who fail to achieve blood pressure control with first-line thiazide diuretic treatment. PMID- 17353514 TI - Endogenous endothelin in human coronary vascular function: differential contribution of endothelin receptor types A and B. AB - Endothelin 1 mediates coronary vasoconstriction and endothelial dysfunction via endothelin receptor type A (ET(A)) activation. However, the effects of selective endothelin receptor type B (ET(B)) and combined ET(A+B) receptor blockade on coronary vasomotion are unknown. We measured coronary vascular tone and endothelium-dependent and -independent vasomotor function before and after selective infusion of BQ-788 (an ET(B) receptor antagonist) or combined infusion of BQ-788+BQ-123 (an ET(A) antagonist) into unobstructed coronary arteries of 39 patients with coronary atherosclerosis or risk factors undergoing cardiac catheterization. BQ-788 did not affect epicardial diameter but constricted the microcirculation (P<0.0001), increased coronary sinus endothelin, and reduced nitrogen oxide levels. In contrast, BQ-123+BQ-788 dilated epicardial (P<0.0001) and resistance (P=0.022) arteries. Responses to acetylcholine and sodium nitroprusside were unaffected by BQ-788 alone. Epicardial endothelial dysfunction improved after BQ-123+BQ-788 (P=0.007). Coronary microvascular responses to acetylcholine and sodium nitroprusside were unaffected by BQ-123+BQ-788. We conclude that selective ET(B) receptor antagonism causes coronary microvascular constriction, without affecting epicardial tone or endothelial function, via reduced endothelin clearance and NO availability. Combined ET(A+B) blockade dilates coronary conduit and resistance vessels and improves endothelial dysfunction of the epicardial coronary arteries. Thus, endogenous endothelin, predominantly via ET(A) receptor stimulation, contributes to basal constrictor tone and endothelial dysfunction, whereas ET(B) activation mediates vasodilation in human coronaries. Our data suggest that selective ET(A) blockade may have greater therapeutic potential than nonselective agents, particularly for treatment of endothelial dysfunction in atherosclerosis. PMID- 17353515 TI - Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism. AB - Albumin excretion marks early glomerular injury in hypertension. This study investigated heritability of albumin excretion in twin pairs and its genetic determination by adrenergic pathway polymorphism. Genetic associations used single nucleotide polymorphisms at adrenergic pathway loci spanning catecholamine biosynthesis, storage, catabolism, receptor action, and postreceptor signal transduction. We studied 134 single nucleotide polymorphisms at 46 loci for a total of >51,000 genotypes. Albumin excretion heritability was 45.2+/-7.4% (P=2x10(-7)), and the phenotype aggregated significantly with adrenergic, renal, metabolic, and hemodynamic traits. In the adrenergic system, excretions of both norepinephrine and epinephrine correlated with albumin. In the kidney, albumin excretion correlated with glomerular and tubular traits (Na(+) and K(+) excretion; fractional excretion of Na(+) and Li(+)). Albumin excretion shared genetic determination (genetic covariance) with epinephrine excretion, and environmental determination with glomerular filtration rate and electrolyte intake/excretion. Albumin excretion associated with polymorphisms at multiple points in the adrenergic pathway: catecholamine biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention, diagnosis, and treatment. PMID- 17353517 TI - What's killing and maiming Canada's youth? PMID- 17353518 TI - Call for arm's-length national research integrity agency. PMID- 17353519 TI - 110 million dollars vaccine research centre to be built in Saskatoon. PMID- 17353520 TI - Mixed reviews for Canada's new food guide. PMID- 17353521 TI - Graduated driver licensing in Canada: slowly but surely. PMID- 17353522 TI - RateMDs.com nets ire of Canadian physicians. PMID- 17353523 TI - Montreal clinic uses public-private payment scheme. PMID- 17353524 TI - Politicians', bureaucrats' drug plans deemed too costly for public formularies. PMID- 17353516 TI - A comprehensive view of sex-specific issues related to cardiovascular disease. AB - Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown. PMID- 17353525 TI - Ten-year trend: surgeries up, hospitalizations down. PMID- 17353526 TI - Stock your emergency department with ice packs: a practical guide to therapeutic hypothermia for survivors of cardiac arrest. PMID- 17353527 TI - Interventional radiology in palliative care. PMID- 17353528 TI - Hygiene: what and why? PMID- 17353529 TI - Canadian breast cancer guidelines: have they made a difference? AB - BACKGROUND: A principal objective of the Canadian Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was to reduce the variation in the way that breast cancer was being treated. To evaluate whether this goal has been reached, we examined variations among surgeons for 4 measures of surgical care and tested for differences in province-wide rates and in variations among surgeons before and after the guidelines were released. METHODS: We studied a population-based cohort of 7022 women living in Manitoba in whom breast cancer was diagnosed from 1995 to 2003 inclusive. Demographic, tumour and treatment information was obtained from the Manitoba Cancer Registry. We examined 4 measures of care: breast-conserving surgery, axillary assessment in invasive disease, axillary node dissection in noninvasive disease and the adequacy of axillary node dissection. Generalized linear models were used to test for significant variations in care among surgeons and to test for differences in province-wide rates and variations in these rates among surgeons before and after introduction of the guidelines. RESULTS: We found clinically significant variations in the province-wide rates of all 4 measures examined. These variations were statistically significant for all measures except axillary node dissection in noninvasive disease. No significant differences in either the province-wide rates or in variations in these rates among surgeons before and after introduction of the guidelines were found for any of the measures. INTERPRETATION: Our results suggest that the Canadian breast cancer guidelines are not meeting their stated objective. New strategies for guideline dissemination and implementation may be required. PMID- 17353530 TI - Inequitable access for mentally ill patients to some medically necessary procedures. AB - BACKGROUND: Although universal health care aims for equity in service delivery, socioeconomic status still affects death rates from ischemic heart disease and stroke as well as access to revascularization procedures. We investigated whether psychiatric status is associated with a similar pattern of increased mortality but reduced access to procedures. We measured the associations between mental illness, death, hospital admissions and specialized or revascularization procedures for circulatory disease (including ischemic heart disease and stroke) for all patients in contact with psychiatric services and primary care across Nova Scotia. METHODS: We carried out a population-based record-linkage analysis of related data from 1995 through 2001 using an inception cohort to calculate rate ratios compared with the general public for each outcome (n = 215,889). Data came from Nova Scotia's Mental Health Outpatient Information System, physician billings, hospital discharge abstracts and vital statistics. We estimated patients' income levels from the median incomes of their residential neighbourhoods, as determined in Canada's 1996 census. RESULTS: The rate ratio for death of psychiatric patients was significantly increased (1.34), even after adjusting for potential confounders, including income and comorbidity (95% confidence interval [CI] 1.29-1.40), which was reflected in the adjusted rate ratio for first admissions (1.70, 95% CI 1.67-1.72). Their chances of receiving a procedure, however, did not match this increased risk. In some cases, psychiatric patients were significantly less likely to undergo specialized or revascularization procedures, especially those who had ever been psychiatric inpatients. In the latter case, adjusted rate ratios for cardiac catheterization, percutaneous transluminal coronary angioplasty and coronary artery bypass grafts were 0.41, 0.22 and 0.34, respectively, in spite of psychiatric inpatients' increased risk of death. CONCLUSIONS: Psychiatric status affects survival with and access to some procedures for circulatory disease, even in a universal health care system that is free at the point of delivery. Understanding how these disparities come about and how to reduce them should be a priority for future research. PMID- 17353531 TI - Canadian breast cancer guidelines are as effective as possible under the circumstances. PMID- 17353532 TI - Mental illness and cardiovascular mortality: searching for the links. PMID- 17353534 TI - Women and cardiovascular disease. PMID- 17353535 TI - Management of acute decompensated heart failure. AB - Acute decompensated heart failure represents a heterogeneous group of disorders that typically present as dyspnea, edema and fatigue. Despite the high prevalence of this condition and its associated major morbidity and mortality, diagnosis can be difficult, and optimal treatment remains poorly defined. Identification of the acute triggers for the decompensation as well as noninvasive characterization of cardiac filling pressures and output is central to management. Diuretics, vasodilators, continuous positive airway pressure and inotropes can be used to alleviate symptoms. However, few agents currently available for the treatment of acute decompensated heart failure have been definitively shown in large prospective randomized clinical trials to provide meaningful improvements in intermediate-term clinical outcomes. Multiple novel therapies are being developed, but previous treatment failures indicate that progress in the management of acute decompensated heart failure is likely to be slow. PMID- 17353536 TI - Health science research in Hungary. PMID- 17353538 TI - Possible patient overlap in studies. PMID- 17353539 TI - Inspired by Banting and Best. PMID- 17353540 TI - Please slow down the CanMEDS express. PMID- 17353541 TI - The 1% solution. PMID- 17353543 TI - Self-managed oral anticoagulation therapy. PMID- 17353545 TI - Avascular necrosis after a steroid injection. PMID- 17353546 TI - Role of matrix metalloproteinases in the acquisition and reconsolidation of cocaine-induced conditioned place preference. AB - Persistent drug seeking/taking behavior involves the consolidation of memory. With each drug use, the memory may be reactivated and reconsolidated to maintain the original memory. During reactivation, the memory may become labile and susceptible to disruption; thus, molecules involved in plasticity should influence acquisition and/or reconsolidation. Recently, matrix metalloproteinases (MMPs) have been shown to influence neuronal plasticity, presumably by their regulation of extracellular matrix (ECM) molecules involved in synaptic reorganization during learning. We hypothesized that inhibition of MMP activity would impair the acquisition and/or reconsolidation of cocaine-conditioned place preference (CPP) in rats. Intracerebral ventricular (i.c.v.) microinjection of a broad spectrum MMP inhibitor, FN-439, prior to cocaine training suppressed acquisition of CPP and attenuated cocaine-primed reinstatement in extinguished animals. In a separate experiment, the cocaine memory was reactivated on two consecutive days with a cocaine priming injection. On these two days, artificial cerebral spinal fluid (aCSF) or FN-439 was administered either 30 min prior to or 1 min after cocaine-primed reinstatement sessions. Infusion of FN-439 partially impaired retrieval of the cocaine-associated context when given 30 min prior to cocaine. In both groups, however, FN-439 suppressed reinstatement compared with controls on the third consecutive test for cocaine-primed reinstatement, when no FN-439 was given. Control experiments demonstrated that two injections of FN-439 + cocaine given in the home cage, or of FN-439 + saline priming injections in the CPP chambers did not disrupt subsequent cocaine-primed reinstatement. These results show for the first time that (1) MMPs play a critical role in acquisition and reconsolidation of cocaine-induced CPP, and (2) rats demonstrate apparent disruption of reconsolidation by an MMP inhibitor after extinction and while they are under the influence of cocaine during reinstatement. PMID- 17353547 TI - Opposing effects on muscarinic acetylcholine receptors in the piriform cortex of odor-trained rats. AB - We combined pharmacological studies and electrophysiological recordings to investigate modifications in muscarinic acetylcholine (ACh) receptors (mAChR) in the rat olfactory (piriform) cortex, following odor-discrimination rule learning. Rats were trained to discriminate between positive and negative cues in pairs of odors, until they reached a phase of high capability to learn unfamiliar odors, using the same paradigm ("rule learning"). It has been reported that at 1-3 d after the acquisition of odor-discrimination rule learning, pyramidal neurons in the rat piriform cortex show enhanced excitability, due to a reduction in the spike-activated potassium current I(AHP), which is modulated by ACh. Further, ACh and its analog, carbachol (CCh), lost the ability to reduce the I(AHP) in neurons from trained rats. Here we show that the reduced sensitivity to CCh in the piriform cortex results from a decrease in the number of mAChRs, as well as a reduction in the affinity of the receptors to CCh. Also, it has been reported that 3-8 d after the acquisition of odor-discrimination rule learning, synaptic transmission in the piriform cortex is enhanced, and paired-pulse facilitation (PPF) in response to twin stimulations is reduced. Here, intracellular recordings from pyramidal neurons show that CCh increases PPF in the piriform cortex from odor-trained rats more than in control rats, suggesting enhanced effect of ACh in inhibiting presynaptic glutamate release after odor training. PMID- 17353548 TI - Reclassification of 300 primary cutaneous B-Cell lymphomas according to the new WHO-EORTC classification for cutaneous lymphomas: comparison with previous classifications and identification of prognostic markers. AB - PURPOSE: In the new WHO-European Organisation for Research and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas three major groups of primary cutaneous B-cell lymphoma (CBCL) are distinguished: primary cutaneous marginal zone B-cell lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL) with a good prognosis, and primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT), with an intermediate-level prognosis. This study aimed to assess the clinical significance of the new classification compared with previous classification schemes (EORTC 1997; WHO 2001) and to define prognostic factors within the newly defined categories. PATIENTS AND METHODS: In the present study clinical data and histologic sections of 300 patients with CBCL, formerly classified according to the EORTC classification, were reviewed and reclassified according to the WHO and the new WHO-EORTC classification schemes. RESULTS: After reclassification, the study comprised 71 patients with PCMZL, 171 patients with PCFCL, and 58 patients with PCLBCL-LT, showing 5-year disease-specific survivals of 98%, 95%, and 50%, respectively. When compared with the EORTC and WHO schemes, 5.3% and 36.3% of patients with CBCL were reclassified into another prognostic category. Multivariate analysis of PCFCL revealed localization on the leg and expression of FOXP1 as independent parameters associated with a poor prognosis. Expression of Bcl-2 or MUM-1 had no significant effect on survival in this group. In PCLBCL-LT, no independent prognostic parameters were found. CONCLUSION: These results emphasize the clinical significance of the WHO-EORTC classification, but suggest that within the group of PCFCL, distinction should be made between lymphomas presenting on the legs and lymphomas presenting at other sites. PMID- 17353549 TI - Abdominal computed tomography predicts progression in patients with Rai stage 0 chronic lymphocytic leukemia. AB - PURPOSE: Whether computed tomography (CT) should be routinely included in the diagnostic work-up in patients with chronic lymphocytic leukemia (CLL) has not yet been determined. The aim of this study was to analyze the prognostic significance of abdominal CT in patients with CLL in Rai clinical stage 0. PATIENTS AND METHODS: Abdominal CT was performed at diagnosis in 140 patients consecutively diagnosed with CLL in Rai stage 0 disease. RESULTS: An abnormal abdominal CT was found in 38 patients (27%). Abnormal CT correlated with increased bone marrow infiltration (P = .024), high lymphocyte count (P = .001), increased ZAP-70 expression (P = .003), and short lymphocyte doubling time (LDT; P = .007). Patients with abnormal CT progressed more frequently and had a shorter time to progression than those with normal CT (median, 3.5 years v not reached, respectively; P < .001) and required earlier treatment intervention. In a multivariate analysis, only high ZAP-70 expression (relative risk = 3.60) and an abnormal abdominal CT (RR = 2.71) correlated with disease progression. CONCLUSION: In this series, an abnormal abdominal CT was a strong predictor of progression in patients with early-stage CLL. The inclusion of CT scans in the initial work-up of patients with early clinical stage on clinical grounds can, therefore, provide relevant clinical information. PMID- 17353551 TI - Childhood cancer in a developing nation. PMID- 17353550 TI - Bortezomib is active in patients with untreated or relapsed Waldenstrom's macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group. AB - PURPOSE: To evaluate the efficacy and toxicity of single-agent bortezomib in Waldenstrom's macroglobulinemia (WM). PATIENTS AND METHODS: Symptomatic WM patients, untreated or previously treated, received bortezomib 1.3 mg/m2 intravenously days 1, 4, 8, and 11 on a 21-day cycle until two cycles past complete response (CR), stable disease (SD) attained, progression (PD), or unacceptable toxicity. Responses were based on both paraprotein levels and bidimensional disease measurements. RESULTS: Twenty-seven patients were enrolled. A median of six cycles (range, two to 39) of bortezomib were administered. Twenty one patients had a decrease in immunoglobulin M (IgM) of at least 25%, with 12 patients (44%) reaching at least 50% IgM reduction. Using both IgM and bidimensional criteria, responses included seven partial responses (PRs; 26%), 19 SDs (70%), and one PD (4%). Total response rate was 26%. IgM reductions were prompt, with nodal responses lagging. Hemoglobin levels increased by at least 10 g/L in 18 patients (66%). Most nonhematologic toxicities were grade 1 to 2, but 20 patients (74%) developed new or worsening peripheral neuropathy (five patients with grade 3, no grade 4), a common cause for dose reduction. Onset of neuropathy was within two to four cycles and reversible in the majority. Hematologic toxicities included grade 3 to 4 thrombocytopenia in eight patients (29.6%) and neutropenia in five (19%). Toxicity led to treatment discontinuation in 12 patients (44%), most commonly because of neuropathy. CONCLUSION: Bortezomib has efficacy in WM, but neurotoxicity can be dose limiting. The slower response in nodal disease may require prolonged therapy, perhaps with a less intensive dosing schedule to avoid early discontinuation because of toxicity. Future studies of bortezomib in combination with other agents are warranted. PMID- 17353552 TI - Placing pain on the sensory map: classic papers by Ed Perl and colleagues. AB - This essay looks at two papers published by Ed Perl and co-workers that identified specifically nociceptive neurons in the periphery and superficial dorsal horn. Bessou P and Perl ER. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol 32: 1025-1043 1969. Christensen BN and Perl ER. Spinal neurons specifically excited by noxious or thermal stimuli: marginal zone of the dorsal horn. J Neurophysiol 33: 293-307 1970. PMID- 17353553 TI - Changes in osmolality sensitize the response to capsaicin in trigeminal sensory neurons. AB - Changes in tonicity in the peripheral nervous system can activate nociceptors and produce pain. Under local inflammatory conditions the peripheral terminals of nociceptors are subject to deviations from isotonicity. Previously it was shown that several members of the TRP(V) family of ion channels are responsive to changes in tonicity. Here we explore how changes in tonicity affect TRPV1 receptor-mediated responses to capsaicin in dissociated rat trigeminal ganglion (TG) neurons. Using whole cell patch-clamp and calcium imaging, we found that mild anisotonicity (260 and 348 mOsm/kg for hypotonicity and hypertonicity, respectively) strikingly sensitized the capsaicin-evoked current, I(caps). Confocal immunolocalization studies also revealed a modest anisotonicity-mediated redistribution of TRPV1 toward the plasma membrane of TG neurons. With respect to downstream signaling pathways, tonicity-induced sensitization of I(caps) was dependent on whether hypo- or hypertonic stimuli were applied. Specifically, antagonism of PKA- and PI3K-activated pathways appreciably reduced the hypertonicity-induced sensitization of I(caps), whereas inhibition of PKC mediated pathways selectively reduced the sensitization produced by hypotonic solutions. In summary, whereas the overall effects of hypo- and hypertonicity resulted in a similar pattern of potentiation of I(caps), intracellular signaling pathways were selective for hypo- versus hypertonicity-induced tuning of capsaicin-activated currents. PMID- 17353554 TI - Activity-dependent initiation of a prolonged depolarization in aplysia bag cell neurons: role for a cation channel. AB - The translation of prior activity into changes in excitability is essential for memory and the initiation of behavior. After brief synaptic input, the bag cell neurons of Aplysia californica undergo a nearly 30-min afterdischarge to release egg-laying hormone. The present study examines a prolonged depolarization in cultured bag cell neurons. A 5-Hz, 10-s action potential train elicited a depolarization of about 10 mV, which lasted or = 500 mg/dL), P-O3FA reduces triglycerides by an average of 45% and very-low-density-lipoprotein cholesterol by more than 50%. Changes in high-density-lipoprotein (HDL) cholesterol and non-HDL cholesterol are usually modest. P-O3FA has been tested in the GISSI-Prevenzione trial - a large, multicenter, open-label, randomized, controlled trial conducted in 11,324 patients. The results of the trial demonstrated significant reductions in all endpoints with the use of P-O3FA. CONCLUSION: P-O3FA has demonstrated an efficacy and safety in adult patients with high and very high triglycerides adjunct to diet, and the reduction in serum triglyceride levels was dependent on the baseline triglyceride levels. A large controlled clinical trial is necessary to determine if P-O3FA can be used to reduce CHD risk, either as combined with hydroxymethylglutaryl-coenzyme A reductase inhibitors or as monotherapy. PMID- 17353569 TI - Deferasirox. AB - PURPOSE: The pharmacology, clinical efficacy, adverse effects and toxicities, and the economic issues that should be considered in using deferasirox are reviewed. SUMMARY: Iron overload is a complication of the chronic blood transfusions used to treat several hematologic disorders. To date, management of transfusional iron overload has consisted of chelation therapy with parenteral deferoxamine. Although survival rates improve with adequate chelation, an estimated one third to one half of patients are not compliant with deferoxamine therapy, largely because of the discomfort and demanding nature of the regimen. In 2005, the Food and Drug Administration approved the labeling for deferasirox for the treatment of chronic overload due to transfusional hemosiderosis. Deferasirox is an oral tridentate chelator that mobilizes iron stores by binding selectively to the ferric form of iron. Deferasirox has been studied in >700 adult and pediatric patients who had transfusion-related iron overload and underlying thalassemia, sickle cell anemia, myelodysplastic syndrome, Diamond-Blackfan syndrome, or another rare anemia. The largest clinical study to date demonstrated the noninferiority of deferasirox 20 or 30 mg/kg/day compared with subcutaneous infusions of deferoxamine >/=35 mg/kg/day administered five days weekly in a subgroup of patients with higher hepatic iron burdens. Deferasirox has been well tolerated in clinical trials. Nearly 97% of participants in a comparative study stated that they preferred deferasirox over their previous deferoxamine treatment. CONCLUSION: Deferasirox, a tridentate oral chelator approved for the treatment of chronic iron overload due to blood transfusions, offers a promising alternative for patients unwilling or unable to comply with deferoxamine therapy. PMID- 17353570 TI - Pharmacist membership in a medical group's diabetes health management program. AB - PURPOSE: An evaluation of the effectiveness of a program at achieving improved glycemic control, lipid levels, and adherence to preventive care measures in diabetes mellitus patients was conducted. SUMMARY: An interdisciplinary diabetes health management program (DHMP) was implemented, which included physicians, clinical pharmacists, registered nurses, and registered dieticians. The patients are seen by a clinical pharmacist with the option of individual or group visits with other members of the multidisciplinary team. Clinical pharmacist interventions include education and comprehensive medication management through collaborative practice agreements held with physicians. The collaborative agreements allow the clinical pharmacist to initiate, adjust, or discontinue pharmacotherapy and order pertinent laboratory tests and podiatry referrals that are within the scope of the medication management protocol. A retrospective review was conducted of the 707 patients enrolled in the program between April 2002 and April 2004. The mean +/- S.D. number of days between baseline and follow up values was 140 +/- 62. Eighty-four percent of the enrolled patients were diagnosed with type 2 diabetes mellitus, 69% met the National Cholesterol Education Program's criteria for metabolic syndrome, and 51% were male. The mean glycosylated hemoglobin (HbA(1c)) value dropped significantly, and the percentage of patients who were at or below the American Diabetes Association's established HbA(1c) goal of < or = 7% increased significantly. Lipid values for enrolled patients improved, with the percentage achieving a low-density-lipoprotein cholesterol concentration of <100 mg/dL increasing from 25% to 44% [corrected] Adherence to preventive care measures (e.g., annual eye and foot examinations) also significantly improved from baseline to follow-up. CONCLUSION: Involvement of pharmacists in an interdisciplinary DHMP has improved patient care. PMID- 17353571 TI - Potential for airborne contamination in turbulent- and unidirectional-airflow compounding aseptic isolators. AB - PURPOSE: The ability of turbulent- and unidirectional-airflow compounding aseptic isolators (CAIs) to control airborne contamination during aseptic compounding of compounded sterile preparations (CSPs) was studied. METHODS: A three-phase challenge of the comparative airborne-contamination management capabilities of five CAIs was conducted using augmented, industry-standard visual tracer and discrete particle counting methods. In phase 1, a visual smoke tracer was used to conduct a standardized, comparative challenge. In phase 2, CAI operational contamination-control capabilities were measured in accordance with the International Organization for Standardization (ISO) class 5 air cleanliness conditions using a standardized CSP process qualification procedure. Alcohol drying times were also compared. In phase 3, the gross contamination clearance interval required to achieve the ISO class 5 condition after a gross contamination event was measured for each CAI. RESULTS: All four unidirectional airflow CAIs met ISO class 5 cleanliness requirements throughout all testing phases and areas of the work zone and demonstrated alcohol drying times of 16 seconds or less. The turbulent-airflow CAI tested failed to achieve the ISO class 5 operating condition at any time during the testing and required alcohol drying times of six minutes. The unidirectional-airflow CAIs tested met the laminar airflow workstation-equivalency requirements of chapter 797 of the United States Pharmacopeia, pharmaceutical aseptic processing standards, the industry-standard definition of a closed isolator, and the rigorous demands of pharmacy and nursing sterile compounding. CONCLUSION: The performance of four unidirectional-flow CAIs supports their use in pharmacy and nursing CSP operations, whereas the performance of one turbulent-flow CAI does not. PMID- 17353572 TI - Evaluation of a pharmacist-managed hepatitis C care clinic. AB - PURPOSE: A description of an effort to create a more time, labor, and cost efficient method for the management of patients with hepatitis C virus (HCV) infection in Department of Veterans Affairs (VA) hospitals is provided; this pilot study also revealed the outcomes of a pharmacist-managed clinic for these patients in comparison to established standards of care. METHODS: A retrospective analysis was performed on data obtained from patients who were referred to the clinic between October 2002 and March 2004 and who had a clinical pharmacist as their primary treatment provider. The patients' medical records were searched for demographic information, disease characteristics, treatment information, treatment and safety information, and virological response. RESULTS: Thirty-one patients were evaluated, and 27 were offered antiviral therapy in the hepatitis C care clinic between October 2002 and March 2004. Of the 27 patients who had sufficient data for analysis, there was a sustained response rate of 63% (17 of 27) overall after treatment with peginterferon and ribavirin combination therapy. Only 3 patients (11%) stopped therapy early secondary to adverse effects, whereas 8 (30%) were managed with growth factors. CONCLUSION: VA patients managed by a clinical pharmacist for the treatment of chronic HCV infection demonstrated similar treatment outcomes compared with the results from earlier studies with VA patients managed with traditional care. Further studies are warranted to investigate the role of the pharmacist in the management of patients with HCV infection. PMID- 17353573 TI - Pharmacoeconomic analysis of caspofungin versus liposomal amphotericin B as empirical antifungal therapy for neutropenic fever. AB - PURPOSE: An analysis was conducted that evaluated and compared the cost differences between caspofungin and liposomal amphotericin B when the medications were used as empirical antifungal therapy for persistent fever during neutropenia. METHODS: Rates of drug use and impaired renal function (IRF) were based on data from published studies. IRF was defined as a doubling of the serum creatinine level or, if the creatinine level was elevated at enrollment, an increase of at least 1 mg/dL. The estimates of the costs for drug acquisition and treating IRF were derived using published data and applied to compare caspofungin with liposomal amphotericin B. Sensitivity analyses were performed by varying the IRF and relative acquisition costs to assess the effect of these factors on the cost differences. RESULTS: The acquisition costs per patient were 6942 dollars for liposomal amphotericin B and 3996 dollars for caspofungin. The estimated cost per patient from IRF was 3173 dollars for liposomal amphotericin B and 793 dollars for caspofungin. Combining drug acquisition and IRF costs, the overall treatment cost per patient for caspofungin was 5326 dollars less than for liposomal amphotericin B. In sensitivity analyses of drug costs, the price of liposomal amphotericin B would have to be 23.95 dollars per vial for the overall treatment costs to be equal. CONCLUSION: Comparison of cost estimates derived from published data revealed that a combined estimate of acquisition costs and costs related to the treatment of IRF was lower for caspofungin than for liposomal amphotericin B for empirically treating patients with neutropenic fever. PMID- 17353574 TI - Stability of an extemporaneously prepared alcohol-free phenobarbital suspension. AB - PURPOSE: The physical and chemical short-term stability of alcohol-free, oral suspensions of phenobarbital 10 mg/mL prepared from commercially available tablets in both a sugar and a sugar-free vehicle was assessed at room temperature. METHODS: Phenobarbital oral suspension 10 mg/mL was prepared by crushing 10 60-mg tablets of phenobarbital with a mortar and pestle. A small amount of Ora-Plus was added to the phenobarbital powder to sufficiently wet the particles. A 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF was combined with the phenobarbital powder to produce a final volume of 60 mL. Three identical samples of each of the two different formulations were prepared and stored at room temperature in 2-oz amber plastic bottles. Immediately after preparation and at 15, 30, 60, and 115 days, the samples were assayed in duplicate by stability-indicating high-performance liquid chromatography. The samples were tasted and inspected for color and odor changes. The percent of the initial concentration remaining at each study time for each phenobarbital suspension was determined. Stability was defined as the retention of at least 90% of the initial concentration. RESULTS: There were no detectable changes in color, odor, and taste and no visible microbial growth in any sample. At least 98% of the initial phenobarbital concentration remained throughout the 115-day study period in both preparations. CONCLUSION: An extemporaneously prepared alcohol free suspension of phenobarbital 10 mg/mL in a 1:1 mixture of Ora-Plus and Ora Sweet or Ora-Sweet SF was stable for at least 115 days when stored in 2-oz amber plastic bottles at room temperature. PMID- 17353575 TI - Pharmacy team providing enhanced services to a transitional care unit. PMID- 17353576 TI - Estimating glomerular filtration rate with a modification of diet in renal disease equation: implications for pharmacy. PMID- 17353577 TI - Effect of dietary phytate on zinc homeostasis in young and elderly Korean women. AB - BACKGROUND: Previous studies suggest that consumption of predominantly plant based diets with high phytate content contribute to zinc deficiency by inhibiting zinc absorption. Age of the individual may also affect the ability to maintain zinc homeostasis. OBJECTIVE: This study was designed to determine the effect of dietary phytate on zinc homeostasis and to evaluate the effect of age on the capacity to maintain the zinc homeostasis with changes in dietary phytate in young and elderly Korean women. DESIGN AND METHODS: Seven healthy young women (22 24 yr) and 10 healthy elderly women (66-75 yr) were studied consecutively for 3 months in 2 metabolic periods (MP) in two different metabolic units. During MP1 the women consumed a high phytate (HP) diet (P:Zn molar ratio = 23) for 9 days. After a 10 d wash-out period at home eating their usual diets, a lower phytate diet (LP) (P:Zn molar ratio = 10) was fed in MP2 for 9 d. Phytase was added to selected foods in the high phytate diet to reduce the phytate content of the meals in the LP period. The zinc content of both diets was about 6.5 mg/d. Stable isotopes of Zn ((70)Zn) were administered intravenously on d 5 of MP 1 and 2 for measuring endogenous fecal zinc excretion. Plasma samples were also collected on d 5 for measuring plasma zinc concentrations by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). 24 hr urine samples were collected for 5 d and complete fecal samples were collected for 9 d after isotope administration. Fractional zinc absorption (FZA) was calculated from mass balance corrected for endogenous fecal zinc (EFZ) excretion and EFZ was determined by using an isotopic dilution technique. Isotopic ratios for FZA and EFZ were measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Statistical analyses were done using ANOVA. RESULTS: Both the young and elderly women were in negative zinc balance during the HP period. This was due to a significant decrease in FZA and total absorbed zinc (TAZ) with a HP diet (43 vs 22% in young women, 34 vs 20% in elderly women, p < 0.001). EFZ excretion did not differ in the young and elderly women during the LP and HP periods. Dietary phytate did not alter plasma zinc concentrations or and urinary zinc excretion in either group. CONCLUSIONS: Adjustments in zinc homeostasis with an increase in dietary phytate did not differ between young and elderly women in this study. PMID- 17353578 TI - Acute smoking induces endothelial dysfunction in healthy smokers. Is this reversible by red wine's antioxidant constituents? AB - OBJECTIVE: Acute smoking causes endothelial dysfunction through impairment of nitric oxide (NO) production, or increased oxidative stress, but the exact mechanism still needs to be elucidated. In healthy non-smokers acute endothelial dysfunction caused by smoking one cigarette was counterbalanced by red wine's antioxidants. The aim of the present study is to investigate whether red wine's antioxidant substances could counteract the acute endothelial dysfunction induced by acute cigarette smoking in healthy smokers as well. METHODS: Twenty healthy volunteers (12 males) participated in a double-blind, cross-over study, comprised of three study days. All subjects either smoked one cigarette, or smoked and drank 250 ml of red wine, or smoked and drank 250 ml of dealcoholized red wine in each one of the study days. Flow mediated dilatation (FMD) was measured at fast and 30, 60 and 90 minutes after each trial. RESULTS: Smoking one cigarette induced a significant decrease in FMD (p < 0.001), which remained significant 30 (p < 0.001), and 60 (p = 0.003) minutes after the end of smoking. FMD remained statistically unchanged after consumption of either regular red wine, or dealcoholized red wine together with smoking. CONCLUSIONS: The observed endothelial dysfunction following smoking of one cigarette was counterbalanced by consumption of either red wine or dealcoholized red wine in healthy smokers. It is possible that acute endothelial dysfunction caused by smoking could be attributed to increased oxidative stress and red wine's antioxidants counteract these acute effects of smoke on endothelium. PMID- 17353579 TI - Use of nutritional supplements among Mexican women and the estimated impact on dietary intakes below the EAR and above the UL. AB - OBJECTIVE: To describe supplement use practices among non-pregnant, non-lactating Mexican women (12-49 y) and estimate their impact on the proportion of women with intakes below the Estimated Average Requirement (EAR) and above the Upper Limit (UL) using data from a national probabilistic nutrition survey in Mexico (1999). METHODS: Information was collected by questionnaire on the frequency and duration of supplement use in the previous 6 months (n = 17,794). Dietary intakes by 24 hour recall were determined in a representative sub-sample (n = 2,599). Frequency of use and available information on the nutrient content of supplements was used to estimate daily equivalent intakes. RESULTS: 17.6% of women reported to have used supplements. The majority of these took supplements once daily (71%) and for < or =2 months (75%). While nutrient intakes from diet alone did not differ between users and non-users, the proportion with intakes of Vitamins A, B(6), B(12), and C, folate, iron, and zinc < EAR were significantly greater among the supplement non-users when intakes from supplements were also considered. The proportion of women with intakes > UL was greater among supplement users than non users for iron, folate and Vitamin B(6). CONCLUSION: Supplement use contributes to the adequacy of nutrient intakes but may also increase the possible risk of toxic intakes of some nutrients among Mexican women. PMID- 17353580 TI - Modifications in postprandial triglyceride-rich lipoprotein composition and size after the intake of pomace olive oil. AB - OBJECTIVE: This study was designed to determine the composition of postprandial triglyceride-rich lipoproteins (TRL) after the intake of pomace olive oil (POO), which is a subproduct of the extraction of virgin olive oil (VOO) and presents a high concentration of minor components with biological activity. METHODS: Meals enriched in POO and refined olive oil (ROO) were administrated to 9 healthy young men and blood was extracted every hour during a postprandial period of 7 hours. Serum and TRL lipid composition were measured by enzymatic and chromatographic methods and apolipoprotein B composition by SDS-PAGE. RESULTS: POO and ROO showed a very similar fatty acid composition but differed in their unsaponifiable fraction. The content of phytosterols, tocopherols, terpenic acids and alcohols and fatty alcohols was much higher in POO than in ROO. Serum lipids were not affected by the administration of the oils but the triglyceride concentration in TRL and the size of the particles (p < 0.05) after POO was higher at time point 2 h and lower at time point 4 h compared with ROO. In contrast, the number of TRL particles was lower after POO, although the rate of clearance was similar. CONCLUSION: We suggest that the unsaponifiable fraction between the two olive oils affect the size and composition of postprandial TRL, which might have a relevant impact on their atherogenicity. PMID- 17353581 TI - The association between adherence to the Mediterranean diet and fasting indices of glucose homoeostasis: the ATTICA Study. AB - OBJECTIVE: We investigated the association between adherence to Mediterranean diet and fasting indices of glucose homoeostasis, in a Greek adult population. METHODS: During 2001-2002 we randomly enrolled 1514 men and 1528 women (18-89 years old) without history of CVD, from the Attica area. Diabetes mellitus (type 2) and impaired fasting glucose (IFG) were defined according to the established ADA criteria. Insulin resistance was evaluated by HOMA-IR. Dietary habits were assessed through a validated food frequency questionnaire and a diet score (range 0-55) was developed (higher values means greater adherence to the Mediterranean diet). RESULTS: The overall prevalence of diabetes type 2 was 7.9% in men and 6.0% in women (P = 0.05). Mean diet score was 26.3 +/- 6.8 in normoglycemic, 25.7 +/- 6.4 in IFG and 22.2 +/- 5.8 in diabetic subjects (p < 0.001). In normoglycemic subjects who were in the upper tertile of the diet score we observed 7% lower glucose (p < 0.05), 5% lower insulin (p < 0.05) and 15% lower HOMA-IR (p < 0.01) levels compared to subjects in the lower tertile of the diet score. Additionally, in diabetic/IFG participants who where in the upper tertile of the diet score we observed 15% lower glucose (p < 0.05), 15% lower insulin (p < 0.05) and 27% lower HOMA-IR (p < 0.01) levels compared to those in the lower tertile. However, multiple regression analysis, adjusted for age, sex, BMI, waist to-hip ratio, physical activity, smoking status, and presence of hypertension and hypercholesterolemia, confirmed the previous associations in normoglycemic, but not in diabetic/IFG people. CONCLUSION: An inverse association was observed between adherence to Mediterranean diet and indices of glucose homeostasis, only in normoglycemic people. PMID- 17353582 TI - Evaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptoms. AB - OBJECTIVES: a) To evaluate the effect of Neptune Krill Oil (NKO) on C-reactive protein (CRP) on patients with chronic inflammation and b) to evaluate the effectiveness of NKO on arthritic symptoms. METHODS: Randomized, double blind, placebo controlled study. Ninety patients were recruited with confirmed diagnosis of cardiovascular disease and/or rheumatoid arthritis and/or osteoarthritis and with increased levels of CRP (>1.0 mg/dl) upon three consecutive weekly blood analysis. Group A received NKO (300 mg daily) and Group B received a placebo. CRP and Western Ontario and McMaster Universities (WOMAC) osteoarthritis score were measured at baseline and days 7, 14 and 30. RESULTS: After 7 days of treatment NKO reduced CRP by 19.3% compared to an increase by 15.7% observed in the placebo group (p = 0.049). After 14 and 30 days of treatment NKO further decreased CRP by 29.7% and 30.9% respectively (p < 0.001). The CRP levels of the placebo group increased to 32.1% after 14 days and then decreased to 25.1% at day 30. The between group difference was statistically significant; p = 0.004 at day 14 and p = 0.008 at day 30. NKO showed a significant reduction in all three WOMAC scores. After 7 days of treatment, NKO reduced pain scores by 28.9% (p = 0.050), reduced stiffness by 20.3% (p = 0.001) and reduced functional impairment by 22.8% (p = 0.008). CONCLUSION: The results of the present study clearly indicate that NKO at a daily dose of 300 mg significantly inhibits inflammation and reduces arthritic symptoms within a short treatment period of 7 and 14 days. PMID- 17353583 TI - Post-therapy profile of serum total cholesterol, retinol and zinc in pediatric acute lymphoblastic leukemia and non-Hodgkin's lymphoma. AB - OBJECTIVE: To assess serum albumin, total cholesterol, retinol, zinc and hemoglobin in children who had completed treatment for acute lymphoblastic leukemia (ALL) and Non-Hodgkin's lymphoma (NHL). METHODS: The above parameters were analyzed in 105 ALL and NHL and 108 age and sex-matched controls. Serum albumin, serum cholesterol and hemoglobin were estimated by colorimetric methods. Serum retinol was estimated by HPLC and serum zinc was estimated by atomic emission spectrophotometer (ICP-AES). Comparisons were made to stage of treatment (maintenance 6 with post-therapy), type of treatment (chemotherapy and radiation with only chemotherapy) and type of malignancy (ALL with NHL). RESULTS: Only serum albumin in patients included at Maintenance(6) was significantly higher (t = 2.31, p = 0.05) than post-therapy patients. No significant difference in serum values was observed by type of treatment. Only total cholesterol was significantly higher in NHL patients than in ALL patients (t = 1.954, p = 0.05). Patients had comparable serum levels to that of controls. However, in patients and controls more than 75% children had deficient serum retinol levels, (< than 0.6989 micromol/l, or 20 microg/dl). Further, 75% patients and 54.7% controls had serum retinol levels less than 0.3439 micromol/l or 10 microg/dl. CONCLUSION: The results of the present study indicate that cancer and its treatment did not have any long-lasting effect on serum albumin, total cholesterol, retinol, zinc and hemoglobin. Majority of subjects had low serum retinol suggestive of depleted liver reserves. The deficient serum retinol levels (< than 0.6989 micromol/l, or 20 microg/dl) in at least 75% of the patients and controls probably reflect poor dietary intake. A higher percentage of patients with low serum retinol levels may also be attributed to the possibility of urinary losses of retinol that occur during episodes of infection while on immunosuppressive anti-cancer drug therapy. PMID- 17353584 TI - Poor nutrient intake and high obese rate in an urban African American population with hypertension. AB - OBJECTIVE: To describe the nutrient intake patterns and general health conditions in an African American (AA) hypertensive population living in Detroit, MI. METHODS: Demographic, anthropometric, general health condition and 3-day dietary recalls were collected from 387 AAs in community-based settings. Only data from 342 participants who met the inclusion criteria were reported. RESULTS: The obesity and type 2 diabetes prevalence in this minority population were significantly higher, and both energy and nutrient intakes were significantly lower than the RDAs or those reported in NHANES. Female participants reported their highest weight at an earlier age but their body weight reduced in the older group. No such trend was observed in male participants. Both males and females consumed significantly fewer servings of fruit, vegetable and grains as recommended by USDA. As household income increased, the consumption of fruits and vegetables were also increased. CONCLUSION: In order to reduce the incidence of obesity and hypertension in this minority population, dietary intervention should begin at adolescence or even earlier. DASH diet would be beneficial for this population. PMID- 17353585 TI - Flaxseed reduces plasma cholesterol levels in hypercholesterolemic mouse models. AB - OBJECTIVE: We examined the effects of whole ground flaxseed added to a Western diet on plasma and hepatic lipids and hepatic gene expression in male and female human apolipoprotein B-100 transgenic (hApoBtg) mice which have a plasma lipid profile more closely resembling man than wild type mice and in mice lacking the low density lipoprotein receptor (LDLr) and apolipoprotein B mRNA editing enzyme complex 1 (LDLr(-/-)/apobec(-/-)). METHODS: The Westernized control diet containing 0.1% cholesterol and 30% kcal as fat was fed for 10 days to hApoBtg mice and for 14 days to LDLr(-/-)/apobec(-/-) mice. Animals from each genetic background were then divided into 2 groups based on gender and mean plasma total cholesterol (TC). The hApoBtg and LDLr(-/-)/apobec(-/-) mice either continued on the control diet for a total of 31 and 35 days, respectively or were fed 20% w/w whole ground flaxseed (flax) with comparable caloric, macronutrient and fiber content for 21 days. Blood was obtained after a 4 hour fast from all mice prior to feeding both control and flax diets, after 10 days on the flax diet, and after 21 days on the flax at which time all mice were exsanguinated. RESULTS: The control diet increased TC by >100 mg/dl in the hApoBtg with a greater increase observed in males and by 800 mg/dl in mice lacking the LDLr. After 3 weeks, the flax diet significantly reduced plasma TC by 19% and 22% in hApoBtg and LDLr(-/ )/apobec(-/-), respectively and non-high density lipoprotein cholesterol (non-HDL C) by 24% in both models (p for all <0.05). Flax significantly reduced hepatic cholesterol in hApoBtg by 32% and 47% in males and females, respectively and LDLr(-/-)/apobec(-/-) mice by 66%. Flax had no effect on the expression of the following hepatic genes: LDLr, 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, phospholipid transfer protein, cholesterol 7alpha hydroxylase, fatty acid synthase, and acyl CoA oxidase in either mouse model. CONCLUSIONS: Flaxseed reduces plasma and hepatic cholesterol in hApoBtg mice, but had no effect on hepatic lipogenic genes and was equally effective in mice lacking LDLr. The combined data suggest that the lipid lowering effect of flax is not hepatic mediated and may be at the level of cholesterol absorption and/or bile acid reabsorption. PMID- 17353586 TI - Validation of a phytoestrogen food frequency questionnaire with urinary concentrations of isoflavones and lignan metabolites in premenopausal women. AB - OBJECTIVE: The purpose of this study was to examine the association between dietary intake of phytoestrogens estimated by a food frequency questionnaire (FFQ) with urinary metabolites. METHODS: Participants were 26 premenopausal, Caucasian women aged 25 to 42 years. Dietary intake of isoflavones (genistein and daidzein) and lignans (secoisolariciresinol and matairesinol) were estimated by a 53-item interviewer-administered FFQ on two occasions, reflecting 'habitual' (previous 2 months) and 'recent' (previous 2 days) dietary intake. Isoflavone (genistein, daidzein) and lignan (enterolactone, enterodiol and secoisolariciresinol) concentrations were measured in 24-hour urine samples by gas chromatography-mass spectrometry. Correlations between FFQ (habitual and recent, separately) and urinary metabolite values were assessed using Spearman correlation coefficients. RESULTS: Mean habitual isoflavone and lignan intakes were 13.7 mg/day and 13.8 mg/day, respectively. Mean urinary concentrations of isoflavones and lignans were 17.4 micromol/day and 20.6 micromol/day, respectively. Recent and habitual isoflavone intakes were correlated with urinary excretion of metabolites (r = 0.64, p < 0.001 and r = 0.54, p = 0.004, respectively). Urinary excretion of lignans was also modestly correlated with recent and habitual lignan intakes (r = 0.46, p = 0.02 and r = 0.40, p = 0.05, respectively). CONCLUSIONS: Our results support the use of this FFQ as a measure of dietary isoflavone and lignan intake in epidemiological studies. PMID- 17353587 TI - FISHing genes and chromosomes from human cells. PMID- 17353588 TI - Application of polymerase chain reaction to detect rearrangement of immunoglobulin heavy chain genes in lymphoproliferative disease. AB - As part of our routine work-up in the diagnosis of lymphoproliferative disease, we used a rapid polymerase chain reaction (PCR) assay to amplify the DNA fragments of the framework 3 (FR3) region of the immunoglobulin heavy (IgH) chain genes. The assay does not involve hybridization, nested priming, or sequencing of the amplified PCR product. It was performed on 66 specimens of B-cell lymphoproliferative disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, hairy cell leukemia and follicular lymphoma. Twenty-six specimens of negative controls, including acute myeloid leukemia, chronic myeloid leukemia in myeloid transformation and idiopathic thrombocytopenic purpura, were also analyzed. The assay was performed with 77% sensitivity and 100% specificity. The standard IgH chain gene rearrangement by Southern blot analysis is reserved for the remaining negative cases if clinically indicated. PMID- 17353589 TI - Electrophysiological findings in newly diagnosed non-insulin-dependent diabetics: A prospective study. AB - This study reports the electrophysiological findings in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) studied in the Neurodiagnostic Laboratory of the King Fahd Hospital of the University (KFHU), Al Khobar, Saudi Arabia. Twenty-nine patients (22 males, 7 females, mean ages 47 and 37 years, respectively) were studied within four weeks of establishing the diagnosis. They were all given nerve conduction studies by the same examiner. Comparison was made with data from a group of 64 normal control subjects. In the study patients, the mean distal sensory peak latency in milliseconds (ms) +/- standard deviation (SD) was 3.5 +/- 0.41 ms in 35 median nerves, 3.2 +/- 0.72 ms in 35 ulnar nerves, 1.9 +/- 0.34 ms in 23 superficial radial nerves and 3.5 7plusmn; 0.61 in 36 sural nerves. The mean distal motor latency +/- SD was 4.6 +/ 0.95 ms in 39 median nerves, 3.5 +/- 0.58 ms in 38 ulnar nerves, 4.8 +/- 1.02 ms in 44 tibial nerves and 6.0 +/- 1.08 ms in 36 peroneal nerves. The electromyogram examination was performed on 24 patients and showed evidence of denervation and/or chronic reinnervation in seven (29%). The frequency of abnormalities in the studied peripheral nerves was 60% for median, 63% ulnar, 33% peroneal, 16% tibial and 8% sural. PMID- 17353590 TI - Demographic and clinical features of diabetes mellitus in 1095 Yemeni patients. AB - The ever-increasing incidence of diabetes mellitus is a cause for growing public health concern in both developed and developing countries. In this study, we aim to explore the special demographic and clinical features of diabetes, as seen in a large sample of Yemeni patients, and to compare these features with those reported in other countries. All patients referred to our diabetic clinic over a five-year period were investigated according to a standardized protocol. Data was collected and fed into a personal computer with a software statistical package for analysis. The relative frequencies of clinical classes of diabetes were 10.5% for IDD, 58.6% for non-obese NIDDM; 26.2% for obese NIDDM, and 4.7% for IGT. In the IDDM class, the age-specific relative frequency rate showed a higher and earlier onset peak frequency in females than in males. Among NIDDM class, about 31% of patients were diagnosed under the age of 45 years, and only 12% were first diagnosed after the age of 65 years. Most NIDDM patients came from social classes I and II (professionals and intermediate professionals) and most IDDM patients came from social class IIIM (skilled manual). A positive family history of diabetes among first-degree relatives of index patients was observed in 33.7% of IDDM patients, in 30% of non-obese NIDDM patients, in 39.2% of obese NIDDM patients and 32% of IGT patients. Female NIDDM patients had a significantly higher mean body mass index (BMI) than males (P<0.0001). Hypertension was recognized in 24.2% of the diabetic population aged 20 to A(3) 65 years. Large vessel disease (LVD) was observed in 28% of patients, small vessel disease (SVD) in 45%, and peripheral neuropathy in 40.7%. Inadequate glycemic control was noticed during follow-up in the majority of patients. Diabetes mellitus in Yemen, especially NIDDM, is characterized by an earlier age at onset, and predominance of males and non-obese NIDM subclass. Other characteristics include moderate genetic susceptibility, inadequate glycemic control and high prevalence of chronic complications. PMID- 17353591 TI - Laparoscopic cholecystectomy: The treatment of choice for cholelithiasis in infancy and childhood. AB - Twelve consecutive laparoscopic cholecystectomies (LC) were performed between January 1994 and October 1996 at King Khalid University Hospital. In all patients the indication for cholecystectomy was symptomatic gallstones. Among the 12 children, six had sickle cell disease. The operating time ranged between 65 and 135 minutes (mean=897plusmn;21.06). There was no major morbidity or mortality. The average duration of postoperative parenteral analgesia (pethidine hydrochloride) required was 0.47+/-0.19 day (ranged between 0.3 and one day). The average postoperative stay was 1.67+/-0.44 days (ranged between 1 and 2.5 days). In conclusion, LC is safe, effective and the preferred approach for cholelithiasis in children, with the advantages of short postoperative analgesia requirement, shorter hospitalization, and therefore, an early return to normal daily activities. PMID- 17353592 TI - Juvenile rheumatoid arthritis: The Saudi Experience. AB - We retrospectively studied the charts of 115 Arab children with juvenile rheumatoid arthritis (JRA), all of whom satisfied the American College of Rheumatology (ACR) criteria for JRA. They were followed between 1978 and 1993 at King Faisal Specialist Hospital and Research Centre and King Khalid University Hospital in Riyadh, Saudi Arabia. All patients were followed up for at least 18 months. The female to male ratio was 1.2:1, and the mean age of onset of the disease was six years. Ninety of the patients were Saudis and the remainder were Middle Eastern Arabs. The mode of onset was systemic in 44%, polyarticular in 30%, and periarticular in 26%. Chronic uveitis was found in only two of the children (1.7%). Antinuclear antibody (ANA) was determined in 96 patients and was positive in 29 (30%). Amyloidosis was not detected in this study population. The clinical and laboratory manifestations of this disease are presented. This review shows that the spectrum of clinical presentation differs in Arab children from those in the West. Systemic and polyarticular onset subtypes were more common, and the incidence of uveitis and amyloidosis was lower. Whether this reflects a genuine difference in the pattern of the disease, or is due to bias in referral pattern, remains to be detected. The answer is currently being sought through an ongoing prospective study. PMID- 17353593 TI - Successful treatment of idiopathic retroperitoneal fibrosis with steroids. AB - Idiopathic retroperitoneal fibrosis (IRF) may cause ureteric obstruction with renal damage. Ureterolysis with intraperitonealization of the ureter is commonly used as primary treatment. We gave corticosteroids for two years to six patients, four males and two females, between 40 and 56 years of age. one of the patients is in his tenth month of treatment and another in the fourth month. Between 4 and 74 months (mean 40.4 months) after initiation of treatment, kidney function had improved, or was preserved in previously functioning renal units, and the patients were free from symptoms. We conclude that steroids may be used as primary treatment of IRF after histological or cytological diagnosis to exclude retroperitoneal malignancy. Steroids should also be part of the treatment strategy in patients with a more aggressive disease who may need surgery. Patients with IRF should be followed for the rest of their lives after discontinuation of steroid therapy. PMID- 17353594 TI - Detection of BCL-2 gene rearrangement in follicular lymphoma by polymerase chain reaction and chemiluminescence technique. AB - The incidence of follicular lymphoma in Saudi Arabia is very low compared to that in Western countries. We analyzed 22 diagnosed cases, based on conventional morphology examination and immunohistochemistry, to detect the Bcl-2 gene rearrangement by polymerase chain reaction (PCR). The DNA was extracted from formalin-fixed paraffin-embedded lymph node tissues by the standard xylene treatment and proteinase K digestion method. Rearrangement of the major breakpoint region was evident in 8 of the 22 cases (36%), determined by visualization of a discrete band hybridized with a chemiluminescence-labeled specific probe. Although the number of cases is small, we believe it denotes a normal detection rate for PCR analysis, using DNA isolated from fixed tissue. With the exception of follicular lymphoma, non-Hodgkin's lymphoma (NHL) analyzed included diffuse large cell lymphoma, lymphoblastic lymphoma, chronic lymphocytic leukemia, mucosa-associated lymphoid tissue and mantle zone lymphomas. No Bcl-2 gene rearrangement was detected in any of these cases. No evidence of Bcl-2 minor cluster sequence gene rearrangement was detected in any of the 38 NHL cases analyzed. PMID- 17353595 TI - Predictors of invasion in ductal carcinoma in Situ of the breast: The value of a scoring system. AB - Ductal carcinoma in situ (DCIS) of the breast shows unpredictable association with invasive ductal carcinoma (IDC). Comedo DCIS (CDCIS) is more frequently associated with IDC than noncomedo DCIS (NCDCIS). We studied prognostic variables in 64 cases of DCIS to identify predictors of invasion. These factors included DCIS type and nuclear grade and two counts of the AgNOR silver staining technique for identification of ploidy and proliferative activity (PA) using two counts: mAgNOR for ploidy and pAgNOR for PA. The other factors included immunostaining of the lesions for epidermal growth factor receptors (EGFR), cathepsin-D (C-D), and the c-erbB-2 oncogene. The 34 cases associated with ICD had pAgNOR ranging from 3% to 36% (median 11%), whereas cases not associated with IDC had a pAgNOR range of 0% to 25% (median 5%; P=0.0001). The correlation between mAgNOR and the development of IDC was less statistically significant. The DCIS type and staining pattern for EGFR, C-D, and c-erbB-2 showed no statistical correlation of individual variables with the development of IDC. A scoring system adding the values of the seven variables was used. A score of 1-2 was given to each variable, depending on whether it was positive or negative. Lesions associated with IDC had a median total score of 8 (+/- 1.35 SD), whereas those lesions not associated with invasion had a median score of 4 (+/- 1.45 SD; P=0.0002). We conclude that proliferative activity analysis may play a significant role in predicting the invasive potential of DCIS. The use of a scoring system adding the sum of single prognostic indicators may provide more useful information regarding the prediction of invasive potential of DCIS than single indicators. PMID- 17353596 TI - Fine-needle aspiration biopsy (FNAB) diagnosis of germ cell tumors: Histologic and cytologic correlations. PMID- 17353597 TI - What's your diagnosis? Mycetomas. PMID- 17353598 TI - Musculoskeletal injuries in a major road accident. AB - The objective of our study was to examine cases of musculoskeletal trauma sustained by survivors of a major road traffic accident (RTA), and evaluate their immediate management. Eighty-four RTA survivors were admitted on a single day at the Asir Central Hospital, Abha, Saudi Arabia. The Division of Orthopedics and Traumatology made an assessment of the various musculoskeletal injuries sustained by the survivors, using the Injury Severity Score (ISS) in the evaluation of their condition. Although RTAs are common in Saudi Arabia, there has been no report about one involving the mass transportation service. Of the 84 patients admitted, 41 (48.8%) had an ISS of over 16, indicating major trauma. Twenty-two of these stayed in the hospital for more than three weeks with a mean ISS of 26.36. Musculoskeletal trauma topped the list, and with neurological injuries were found to be a major contributing factor for long hospital stay. Our paper describes the primary management of the musculoskeletal injuries and suggests measures to prevent morbidity relating to these injuries. PMID- 17353599 TI - Primary hyperoxaluria type 1 and urolithiasis in children: Report of three cases. PMID- 17353600 TI - Maffucci's syndrome. PMID- 17353601 TI - Colonic volvulus: An unusual presentation of malrotation. PMID- 17353602 TI - Hyperparathyroidism in a patient with Maffucci's syndrome: A case report. PMID- 17353603 TI - A rare cause of upper gastrointestinal tract bleeding. PMID- 17353604 TI - Cervical pregnancy presenting as a missed abortion. PMID- 17353605 TI - Pediatric pulmonary Gaucher disease: Two patterns of lung involvement. PMID- 17353606 TI - Oval window agenesis. PMID- 17353607 TI - Upper gastrointestinal diseases in symptomatic Jordanians: A prospective endoscopic study. PMID- 17353608 TI - A recommended method for management of foot pain using custom-made insoles. PMID- 17353609 TI - High incidence of type 1 diabetes mellitus in Sudanese children, 1991-1995. PMID- 17353610 TI - Esophageal atresia and tracheoesophageal fistula. PMID- 17353612 TI - Prevalence and etiology of childhood sensorineural hearing loss (SNHL) in Riyadh. PMID- 17353611 TI - Abnormal electrophoretic pattern of glycosylated hemoglobin in sickle cell disorders. PMID- 17353613 TI - Trancheal stenosis. PMID- 17353614 TI - Reply: Prevalence and etiology of childhood sensorineural hearing loss (SNHL) in Riyadh. PMID- 17353615 TI - Survey of medical research publications. PMID- 17353616 TI - Antibiotics: A need for regional surveillance and a control program. PMID- 17353617 TI - Soda lime canister hazard: Heed the warning label! PMID- 17353618 TI - Secondary cardiac hemochromatosis in Saudi patients. PMID- 17353624 TI - [DNA repair as a determinant of tumour chemosensitivity]. AB - Differently from target-based anticancer drugs, molecular mechanisms of actions are not well-known in many of the classical antineoplastic agents. With the exception of vinca alkaloids and taxanes, all of the classical antineoplastic agents work on DNA metabolism in cells and can therefore be categorised as 'DNA metabolism inhibitor'. Cellular sensitivity against these drugs largely depends on various activities in DNA metabolism, particularly in DNA repair. However, DNA repair as a determinant of drug sensitivity had long received little attention. DNA mismatch repair (MMR) is now regarded as an important determinant to alter cellular sensitivities against various drugs including fluoropyrimidines, platinum compounds and topoisomerase inhibitors. However, molecular mechanisms of this connection are still unknown. In particular, the relationship between MMR and 5-fluorouraci (l 5-FU) sensitivity is now being approached by examining the tumour MMR status and clinical outcomes in colorectal cancer patients treated with 5-FU-based adjuvant chemotherapies. However, reported results lack consistency, possibly due to the methodological problems in assays used to determine the MMR status. On the other hand, nucleotide excision repair (NER) is also regarded as an important determinant of cisplatin (CDDP) sensitivity. Expression of ERCC 1, a component of this complex multi-protein system, has been reported to be a determinant of prognosis in CDDP-treated non-small-cell lung cancer patients. In order to establish the significance of DNA repair as a determinant of tumour chemosensitivity, further basic studies, particularly ones approached from biochemical viewpoints, are required. Clinical studies supported by accurate assay techniques are also needed. PMID- 17353625 TI - [Hematological malignancies]. AB - The same progress in the recent therapeutic strategy for older adults with hematological malignancies has also been seen in younger adults. The standard initial therapy for elderly acute promylocytic leukemia is the combination with all-trans retinoic acid and anthracyclines. For other acute myeloid leukemias (AML), many trials of combination chemotherapy have not improved the outcome of elderly patients. Gemtuzumab ozogamicin,which is an immunoconjugate binding to CD 33 on the surface of AML blasts, has produced good results for elderly patients in either monotherapy or in combination with conventional chemotherapeutic drugs. One of the BCR-ABL tyrosine kinase inhibitors, imatinib mesylate, is active for elderly Philadelphia-positive leukemia including acute lymphoblastic leukemia and chronic myeloid leukemia. In the treatment of elderly diffuse large B cell lymphoma, combination of rituximab and cyclophosphamide+doxorubicin+vincristine+prednisone (CHOP) has become the therapy of choice based upon a Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial even though there are some other trials for elderly patients such as dose-dense CHOP therapy. For follicular lymphoma, combination therapies of rituximab and cytotoxic drugs such as R-CHOP and R-CVP are also considered as promising therapies. For the management of multiple myeloma, high-dose chemotherapy, mainly melphalan with autologous stem cell transplantation, has become the standard treatment even for elderly patients less than 65 years of age. PMID- 17353626 TI - [Lung cancer]. AB - Aging society is coming now, the ratio of elderly patients among all lung cancer patients has currently been increasing. It is necessary for elderly patients who are under-represented in clinical trials to study their suitable regimen. Thus, phase II and III clinical trials have been performed specifically for elderly non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients all over the world. As for single agent chemotherapy, there is a strong rationale for docetaxel and vinorelbine in elderly patients with advanced NSCLC. Recently, there are phase I and II clinical trial for CPT-11 monotherapy, and gefitinib and TS-1 are reasonable options for elderly patients. Alimta is tolerable for elderly, and subset analysis is performed for the elderly with recurrent NSCLC. As platinum-based chemotherapy, there are several elderly subset analyses and JCOG 0207, which is a phase III trial now in progress comparing weekly cisplatin+weekly docetaxel and weekly docetaxel. In SCLC, there is no evidence of single agent chemotherapy but combination chemotherapy such as carboplatin+etoposide is recommended. A phase III study of carboplatin+etoposide versus amrubicin under way. These studies should aim to optimize several agents for elderly patients and prolong survival, palliative care. PMID- 17353627 TI - [Medical treatment for older breast cancer patients]. AB - The incidence of breast cancer and the percentage of the population 65 years of age or older is increasing in Japan. So many elderly patients with breast cancer are given medical treatment. The first-line treatment for elderly patients with hormone responsiveness is endocrine therapy prior to cytotoxic chemotherapy in principle. In terms of chemotherapy, treatment for elderly patients should not be avoided simply because of their age. Oncologists must determine whether chemotherapy should be prescribed after they assess the benefits and risk, including comorbidity and life expectancy, in elderly patients. In future, combinations with low harm treatments, including biologic agents, should be considered in treatment strategy for elderly patients with breast cancer. PMID- 17353628 TI - [Chemotherapy for elderly patients with colorectal cancer]. AB - The number of elderly patients with colorectal cancer is increasing in Japan. Until recently, chemotherapy was not adapted for older patients. Today, older patients have opportunity to receive new regimen with newly developed agents and improvement of supportive therapy. UFT/leucovorin therapy has been shown to be as effective and equally tolerated in elderly patients as in younger patients. There is no difference between older and younger patients in efficacy and toxicity of FOLFOX 4 (oxaliplatin plus 5-FU and leucovorin) Bevacizumab with 5-FU and leucovorin is also tolerable and effective for elderly patients. It is necessary to evaluate the possibility of new molecular target agents for treatment for super-elderly patients (>80 years). Increasing cost of the new agents will pose economical problem to resolve specially for older population. PMID- 17353629 TI - [Optimal treatment for elderly high-risk prostate cancer patients]. AB - In this paper, we summarize the options of conservative systemic medical therapy in elderly patients with prostate cancer. Treatment was classified into three categories: 1) endocrine therapy, 2) systemic chemotherapy, and 3) treatment using other drugs. 1) The common endocrine therapy called CAB (combined androgen blockade) consisting of androgen ablation with medical or surgical castration using anti-androgen agents will be considered first. It is important to minimize or eliminate the side effects of hormonal therapy in elderly patients. Therefore,monotherapy with anti-androgen agents, intermittent CAB, watchful waiting and delayed CAB, sequential usage with LH-RH (luteinizing hormone releasing hormone) and anti-androgens will be considered. In hormone refractory prostate cancer, estramustine may be administered as an estrogen effect is expected. 2) Recently, systemic chemotherapy such as docetaxel regimens has prolonged survival and chemotherapy should be considered as the next step. There are, however, a variety of controversial issues in elderly patients such as the suitable timing of induction and the optimal dose, interval and schedule. It is also unclear whether docetaxel alone should be administered or combined with estramustine, steroid or bisphosphonate. We have performed intermittent chemotherapy, consisting of docetaxel with estramustine, and this regimen has been tolerated well and resulted in a good quality of life. 3) Additional therapy such as steroids and bisphosphonate may be administered to improve the quality of life. We have listed the major treatment options for prostate cancer, reviewed the expectation induced by each treatment and outlined key issues pertaining to usage in elderly patients. PMID- 17353630 TI - [The safety of docetaxel with cyclophosphamide (TC) therapy as adjuvant chemotherapy for Japanese women with operable breast cancer]. AB - The safety of docetaxel (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) every three weeks (TC) as adjuvant therapy for Japanese women with operable breast cancer was evaluated. Ehime TC Study Group initiated the randomized control study,which compared the effects of the TC course number (4 cycles versus 8 cycles) in the adjuvant setting on the treatment outcomes of breast cancer patients. Eight patients were investigated on the side effects of TC therapy, four of them were allocated to 4 cycles of TC, and four to eight cycles from May, 2004 to Feb. 2005. Leukocytopenia and neutropenia of grade 3 or 4 were seen in 50% and 63% of the cases, respectively. No febrile neutropenia was seen. Although the non-hematological side effects of grade 3 or 4 were not observed, alopecia, stomatitis, skin toxicities and edema of grade 2 were seen in 100%, 25%, 25%, 13% of cases, respectively. TC therapy was well tolerated. All anticancer drugs could be administered as scheduled. From these preliminary results, TC therapy seems to be able to be safely prescribed postoperatively for Japanese women operated for breast cancer. PMID- 17353631 TI - [A retrospective study of irinotecan plus fluorouracil and l-leucovorin chemotherapy for advanced and metastatic colorectal cancer]. AB - We have treated 14 advanced and metastatic colorectal cancers with irinotecan (CPT-11) plus fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. The 14 patients consisted of 8 males and 6 females with a mean age of 65 years. We diagnosed adenocarcinoma of the colon in 10 patients and of the rectum in 4 patients. Four patients had liver metastases, five had lung metastases, and one had both, while one had lung and lymph node metastases, two had lymph node metastases and one had a local recurrence. The chemotherapy consisted of CPT-11 100 mg/m(2) div, as a 150-minute infusion, simultaneously l LV 10 mg/m(2) div, as a 30-minute infusion, followed by 5-FU 500 mg/m(2) iv, as a bolus injection. This treatment was administered weekly for 2 weeks followed by a 2-week rest period and repeated every 4 weeks. All patients received this regimen as first-line chemotherapy. All patients were evaluated for efficacy 1 CR, 2 PR, 9 SD, and 2 PD. The overall response rate was 21.4% with a median time to progression of 8.1 months and a median survival time of 18.6 months. Grade 3 nausea, diarrhea and the suppression of white blood cells were seen in 3 patients, respectively. All other adverse reactions were mild (grade 1 or 2). Except for one patient,residual patients were able to receive the systemic chemotherapy on schedule. CPT-11/5-FU/l-LV combination chemotherapy appears to be effective first-line chemotherapy for advanced and metastatic colorectal cancer. PMID- 17353632 TI - [Comparison of antiemetic efficacy of 5-HT3 receptor antagonists in orthopedics cancer patients receiving high-dose chemotherapy]. AB - There are no reports comparing the efficacy of 3 selective 5-HT(3) receptor antagonists (Granisetron, Ondansetron, and Ramosetron). We designed a prospective study to compare the efficacy of Granisetron, Ondansetron, and Ramosetron. Thirteen patients gave informed consent to participate in the study. We assigned them to groups taking Granisetron, Ondansetron, or Ramosetron before the high dose chemotherapy. They themselves reported the extent of their nausea and how many times they vomited per day from the first to the sixth day of chemotherapy. We evaluated their report with PLS (Partial Least Squares) and Welch's t-test. From the results of PLS, it was suggested that CDDP contributed the most and Ramosetron the least to the extent of nausea, while Doxorubicin (ADM)/CDDP contributed the most and Ramosetron the least to the frequency of vomiting. Then we compared the antiemetic effect of the agents regarding the types of chemotherapy. It was concluded that Ramosetron might have been the most effective of the three agents in reducing nausea and vomiting, but with no significant difference. PMID- 17353633 TI - [Benefits of TS-1 plus leucovorin combination therapy for colorectal cancer: evaluation of therapeutic effect of TS-1 and leucovorin combination therapy using rodent model fed a low folate diet]. AB - We evaluated the therapeutic effect of TS-1, a novel oral fluoropyrimidine, in combination with leucovorin with in vivo experiments using a murine tumor xenograft model fed a low folate diet. The reduced folate levels in the tumors of mice fed a low folate diet were significantly lower than those in the tumors of mice fed a normal diet. In addition, the basal reduced folate levels in the tumors of mice fed a low folate diet were comparable to those in human colorectal cancer tissues. Furthermore, when leucovorin was orally administered, the reduced folate levels in the tumors of mice fed a low folate diet were more than two-fold higher than those of mice fed the normal diet. The leucovorin-induced potentiation of TS-1 antitumor activity was obviously higher in COL-1 tumor bearing mice fed a low folate diet than in mice fed a normal diet. The remarkable increase in reduced folate levels following the administration of leucovorin contributed to the leucovorin-induced potentiation of TS-1 antitumor activity in this low-folate-diet animal model. These results suggest that rodent models fed a low folate diet are suitable for in vivo evaluation of reduced folate drugs like leucovorin. In this model, the combination of leucovorin with TS-1 resulted in a higher antitumor efficacy than TS-1 alone or the combination of UFT and leucovorin, suggesting that TS-1 and leucovorin combination therapy may be an effective regimen for patients with colorectal cancer. PMID- 17353634 TI - [Recurrent esophageal cancer with complete response to TS-1 chemotherapy]. AB - An 80-year-old man was admitted to our hospital for treatment of recurrent esophageal cancer in December, 2004. He was diagnosed as having esophageal cancer of stage IVa (T2N4M0) in October, 2002, and he received chemoradiotherapy (nedaplatin (CDGP)/5-fluorouracil (5-FU) total 6 course+60 Gy). Afterwards, lymph nodes recurred, and two courses of CDGP/vindesine were given. Then, the primary lesion showed a complete response (CR), and lymph nodes a partial response (PR). In December, 2004, paraesophageal lymph nodes were enlarged to the size of 7 cm. On admission, because of renal disturbance and dementia with advanced age, we chose chemotherapy with TS-1 (100 mg/body/day, three weeks of administration, then two weeks of withdrawal). He had adverse effects of hematotoxicity of grade 3, and non-hematotoxicity of grade 1. He received 6 courses of this regimen and eventually showed CR. Serum SCC was decreased from 4.7 ng/mL to 0.9 ng/mL. At present,the lesions have not recurred during the follow-up for 18 months. PMID- 17353635 TI - [A case of adenosquamous gastric carcinoma successfully treated with TS-1, low dose CDDP and docetaxel as neoadjuvant chemotherapy]. AB - The patient was a 66-year-old male with extremely advanced gastric cancer type 3 and diagnosed with adenocarcinoma by endoscopic biopsies specimens. Combined chemotherapy of TS-1, CDDP and docetaxel was prescribed in order for tumor reduction and downstaging. TS-1 (80 mg/m(2)) was administered 28 days followed by 14 days rest as one course. CDDP (8 mg/m(2)) was administered on days 1, 2, 14 and 15 and docetaxel (40 mg/m(2)) was administered on day 1 and 14, followed by 4 weeks rest as one course. After 2 courses of treatment, a CT scan revealed a minor response of tumor reduction. Therefore, total gastrectomy, partial pancreas body and tail resection, and D 2 lymph node dissection were performed. The patient had undergone adjuvant chemotherapy of TS-1 and biweekly docetaxel after surgery with no recurrence for 13 months. Adverse reactions were grade 3 neutropenia and grade 2 diarrhea. Combined chemotherapy of TS-1, low-dose CDDP and docetaxel were intensive and required constant patient monitoring. However, it proved effective and feasible as a neoadjuvant chemotherapy regimen for advanced gastric cancer. PMID- 17353636 TI - [Complete response in an elderly patient with advanced gastric cancer treated with TS-1]. AB - The patient was an 80-year-old man whose complaint was coffee-grounds vomit. He was diagnosed with advanced gastric cancer, T2N1H0P0M0, stage II. Though the curative operation was explained to the patient, he declined it because of complications of advanced age, diabetes and bronchial asthma; chemotherapy was chosen instead. TS-1 (80 mg/day) was administered for 28 days, followed by 14 days rest as one course. A partial response was observed after the first course, and no cancer cells were confirmed by endoscopic biopsy after the fifth course. Moreover, after the 14th course, CT showed a complete regression of lymph node metastasis, and no cancer cells were confirmed by endoscopic biopsy, for a complete response (CR). From now on, as society grays more and more, it is considered that elderly advanced gastric cancer patients with complications will increase. TS-1 single treatment is considered to be safe and outpatient treatment possible as one of the useful cures. PMID- 17353637 TI - [Combination therapy with bi-weekly docetaxel and 5'-deoxy-5-fluorouridine for advanced gastric cancer]. AB - Recently, new and promising antitumor agents such as TS-1, CPT-11, and taxanes have been widely used and have contributed to the survival of unresectable and recurrent gastric cancer patients. However, problems remain in the treatment for patients showing multi-drug resistance to those agents. We have experienced five patients with unresectable and recurrent gastric cancer, treated with combination therapy with bi-weekly docetaxel and 5'-deoxy-5-fluorouridine (5'-DFUR). The therapy was introduced as a 2nd, 3rd, 4th, and 6th chemotherapy regimen. Among five cases, one showed a moderate response and two exhibited stable disease, while two suffered progressive disease. Although the performance status at the start of the therapy was "2" in three cases and "1" in two cases, there were no serious adverse events in any case, and all patients were treated at an outpatient clinic. Three cases were introduced to the regimen as final treatment and survived for 209, 246, and 157 days, respectively. Combination therapy with bi-weekly docetaxel/5'-DFUR can be a promising regimen for gastric patients showing multi-drug resistance and poorer performance status. PMID- 17353638 TI - [A patient with advanced recurrent breast cancer who firmly resisted hair loss and was then treated by combination therapy with high-dose toremifene and capecitabine]. AB - The patient was a 36-year-old woman, who found a mass in her right breast around April 2002, visited a physician in June, and was referred to our department because of suspected right breast cancer. It was confirmed that the cancer had metastasized to the right axillary lymph nodes and the skin of the right breast. After undergoing an operation on July 11 (Bt+Ax), the patient was placed on tamoxifen (TAM). Then, the course was followed while the patient was treated with CEF and 5'-DFUR. In April 2004, she had a recurrence manifesting itself as bone metastasis, partly because of poor compliance with the hospital-visit and dosing schedules. After chemotherapy with paclitaxel, etc., combination therapy with docetaxel (DOC), capecitabine, and high-dose (120 mg/day) toremifene (TOR) was started on October 15, 2004. Subsequently, because the patient firmly resisted hair loss, chemotherapy was continued with a double-drug regimen with capecitabine and high-dose TOR. Treatment was temporarily discontinued because the patient developed hand-foot syndrome, which was probably attributable to capecitabine, but the symptoms improved after administration of vitamin B(6). Thereafter,the patient complied well with the dosing schedule, and no new metastatic focus has been detected by any examination as of October 2005. These findings suggest that the double-drug regimen with capecitabine and high-dose TOR is an effective treatment for patients who can not be treated with anthracyclines or taxanes. PMID- 17353639 TI - [A case of carcinomatous cardiac tamponade due to breast cancer treated with OK 432 and mitomycin C]. AB - The patient was a 40-year-old woman who was admitted to our hospital because of severe cough and dyspnea due to multiple lung metastases from breast cancer, who had undergone Auchincloss operation for right breast cancer about five years earlier. While systemic chemotherapy (CAF) was started after admission,she presented with cardiac tamponade. A cardiac echogram revealed marked retention of pericardial effusion. Pericardiocentesis was carried out, and the cytology of the effusion showed class V, resulting in the diagnosis of carcinomatous cardiac tamponade due to breast cancer. She was treated with intrapericardial chemotherapy using OK-432 and mitomycin C (MMC), and has not suffered from pericardial effusion after the intrapericardial chemotherapy. Intrapericardial chemotherapy using OK-432 and MMC may be very useful for malignant pericardial effusion. PMID- 17353640 TI - [A resected case of squamous cell carcinoma of the breast successfully treated by FU plus cisplatin (CDDP) adjuvant therapy against recurrent metastases]. AB - A resected case of squamous cell carcinoma associated with ductal carcinoma in the hemilateral breast successfully treated by FU plus cisplatin (CDDP) adjuvant therapy against recurrent metastases is reported with some discussion. A 42-year old woman was admitted to our hospital because of right breast tumor. By physical examination, mammography, ultrasound examination and aspirated cytology, we diagnosed squamous cell carcinoma of the right breast. Before operation SCC antigen was elevated. Standard mastectomy was performed, and SCC antigen was decreased within normal range. Then, a standard regimen of chemotherapy using docetaxel with anti-hormonal therapy by LH-RH analog and tamoxifen was done as first-line adjuvant therapy. Four months after operation the SCC antigen level was elevated again, and recurrence of cancer (skin and liver metastases) was recognized. Next, we tried 5-FU/UFT plus CDDP for squamous cell carcinoma of other organs such as the esophagus. These anti-tumor drugs proved effective, and no metastasis of the skin was detected thereafter, and liver metastatic lesion was decreased in ten months. The SCC antigen level was within the normal range again. Additionally, when metastases redeveloped, TS-1 plus CDDP controlled growth of tumors in seven months. Based on the present findings,we recommend adjuvant chemotherapy by FU plus CDDP for squamous cell carcinoma of the breast. PMID- 17353641 TI - [A case of advanced breast cancer with multiple liver metastases resistant to chemotherapy responding to high-dose toremifene]. AB - A 47-year-old woman was admitted to our hospital for advanced breast cancer with multiple liver metastases and liver dysfunction in January 2004. EC (EPI combined with CPA), weekly PTX, and AI were performed but were not effective for that tumor. Therefore, high-dose TOR was started. Liver dysfunction recovered after administration of TOR, and primary tumor and liver metastases were evaluated as a partial response (PR). The same therapy has been performed for six months with no evidence of deterioration. PMID- 17353642 TI - [The efficacy and safety of docetaxel for elderly advanced breast cancer patients]. AB - We studied the efficacy and safety of docetaxel (DOC) for elderly breast cancer patients. Between September 1997 and June 2003, five consecutive women with advanced breast cancers who were 75 years of age or older received DOC at a dose of 60 mg/m(2) every three weeks. No premedications to prevent hypersensitive reactions and fluid retention by DOC were given. The number of DOC dosages per case was 5-16 times (12 times the median) and the relative dose intensity (RDI) was 80-100% (95% of medians). Objective partial responses were observed in all patients. The median time to partial response was 21 days (range: 21-50 days). The median time to treatment failure was 12 months (range: 5-22 months). The grade and the frequency of major side effects were the following: leukocytopenia of grade 3 (80%), edema of grade 2-3 (40%), and alopecia of grade 2 (100%). It was concluded from these findings that DOC could be safely and effectively administered to elderly advanced breast cancer patients. PMID- 17353643 TI - [A case of advanced clear cell carcinoma of the endometrium that responded remarkably to neoadjuvant chemotherapy of combination carboplatin plus weekly paclitaxel]. AB - Clear cell carcinoma of the endometrium is a very rare and highly malignant neoplasm that accounts for less than 5% of endometrial carcinoma. Survival of patients in the advanced stage is poor, and the treatment of choice is not clear. We report the case of a 62-year-old woman who had Stage IVb advanced clear cell carcinoma of the endometrium with multiple lung metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy of combination carboplatin (CBDCA) (AUC 5, day 1) plus weekly paclitaxel (PTX) (70 mg/m(2), day 1, 8, 15). After 3 courses of chemotherapy, the uterine tumor was obviously reduced, and lung metastases had disappeared. Therefore, she underwent the operation. The current case suggests that combination CBDCA plus weekly PTX is effective against advanced clear cell carcinoma of the endometrium. PMID- 17353644 TI - [A recurrent ovarian cancer patient who achieved a complete response following irinotecan plus CDDP therapy]. AB - A 78-year-old patient had abdominal bloating since October 2002, and visited a GP, who noticed ascites, and referred the patient to our hospital. An exploratory laparotomy was performed and stage IIIc ovarian cancer was diagnosed. Six courses of docetaxel-carboplatin (DJ) chemotherapy were administered; however, the lesion was assessed as progressive disease (PD), and 24 courses of weekly paclitaxel were then administered. During the follow-up as an outpatient, a tumor marker increased again. Weekly paclitaxel was not effective this time, and the lesion was assessed as PD. The patient therefore received treatment with irinotecan and cisplatin (CPT-11+CDDP). These drugs have different mechanisms of action. The CA 125 level returned to normal following four courses of CPT-11+CDDP. The patient received a total of six courses, and thus far, no obvious recurrent lesion has been observed. These results suggest that CPT-11+CDDP may be effective against recurrent ovarian cancer, which is difficult to treat due to its resistance to platinum drugs and taxane drugs. PMID- 17353645 TI - [Weekly paclitaxel therapy is curative for patients with retroperitoneal liposarcoma]. AB - In March 2004, we resected a giant retroperitoneal liposarcoma and the transverse colon, spleen and left kidney in a 58-year-old woman. In July, recurrence was detected in the right pelvis and left upper abdomen; therefore, we resected the tumor. In September 2004, computed tomography (CT) revealed multiple recurrences in the right lower abdomen, left upper abdomen, front of the left lobe of the liver, and at the back of the stomach. In October 2004, we started mesna, doxorubicin, ifosfamide, and dacarbazine therapy (MAID); however, after 1 course, the disease progressed, and the patient developed edema in the bilateral legs due to inferior vena cava (IVC) compression. In November 2004, we started weekly paclitaxel therapy (100 mg/m(2), once a week for 3 weeks followed by 1 drug-free week). CT revealed no change as a result of chemotherapy; however, IVC compression had improved, and leg edema had decreased. In August 2005, chemotherapy was stopped; therefore,the patient's condition worsened. She died in September 2005. We performed weekly paclitaxel therapy for the patient with recurrent liposarcoma. This improved her symptoms and quality of life (QOL). Therefore,we consider weekly paclitaxel therapy to be effective for liposarcoma treatment. PMID- 17353646 TI - [Interdigitating dendritic cell sarcoma/tumor--a case report]. AB - We report an extremely rare case of interdigitating dendritic cell sarcoma/tumor (IDCS). A 52-year-old man presented with a 2-week history of fever in January 2002. Physical examination revealed enlarged, painless right axillary lymph nodes, and hepatosplenomegaly. Whole-body computerized tomography showed enlarged lymph nodes in mediastinal, right axillary, abdominal para-aortic, ileum, and inguinal regions. Hepatosplenomegaly was also detected. In addition to abnormal liver function tests, serum levels of soluble interleukin-2 receptor and ferritin were elevated. Excisional biopsy of right axillary lymph node was performed in February 2002. Histological examination showed a diffuse proliferation of medium to large-sized cells with round or oval nuclei and abundant cytoplasm. Spindle shape cells and Hodgkin-like giant cells were also seen. Immunohistochemically, the tumor cells expressed S-100 protein, CD 68, and CD 45 RO. They were negative for CD 1, CD 3, CD 15, CD 20, CD 21, CD 23, FDC, DRC, and p80. These findings were compatible with the diagnosis of IDCS. The patient was treated with polychemotherapy consisting of doxorubicin,cyclophosphamide, vincristine, and prednisone. However, he developed fungal pneumonia and died of respiratory failure 1 month after the start of treatment. PMID- 17353647 TI - Blood pressure determination by traditionally trained personnel is less reliable and tends to underestimate the severity of moderate to severe hypertension. AB - OBJECTIVE: Blood pressure determined by nurses has been observed to be unreliable. This study was conducted to compare the reliability of blood pressure measurements performed by traditionally trained nurses with those performed by a well-trained nurse and by an automatic device. METHODS: Hypertensive patients in an outpatient clinic were studied. Each individual was subjected to three blood pressure measurements: the first one was performed by the traditionally trained nurse on duty at the time of study (TT nurse BP), the second one by a specifically trained nurse (ST nurse BP), both using sphygmomanometer; and the third one was done using Omron HEM-907 (digital BP). RESULTS: A total of 907 participants were enrolled. More than 99% of both systolic and diastolic TT nurse BP ended with zero, demonstrating that they had terminal digit preference. ST nurse BP was in better agreement with digital blood pressure measurement than with TT nurse BP. The number of differences of < or =5 mmHg between ST nurse BP and digital blood pressure measurement was approximately 60% for both systolic and diastolic blood pressure. Overall, traditionally trained nurses overestimated, rather than underestimated, blood pressure. However, systolic blood pressure underestimation was extremely prominent in participants with moderate to severe hypertension. Systolic blood pressure underestimation of >5 mmHg was as high as 57.5% by traditionally trained nurses versus 33.8% by the automatic device, indicating that traditionally trained nurses tended to underestimate blood pressure in participants with more severe hypertension. PMID- 17353648 TI - Ambulatory blood pressure monitoring early after acute myocardial infarction: development of a new prognostic index. AB - OBJECTIVES: The aim of our study was to assess the possible role of a prognostic index based on ambulatory blood pressure monitoring in a large cohort of patients with recent myocardial infarction. METHODS: The study population included 1335 consecutive patients admitted for ST elevation myocardial infarction and discharged alive from 48 Italian hospitals participating in the multicentric IMPRESSIVE (Infarto Miocardico, Pressione arteriosa e frequenza cardiaca. Studio Italiano di Valutazione Epidemiologica) study. Ambulatory blood pressure monitoring was performed 3 weeks after discharge, with a clinical follow-up of 12 months. End-points included cardiac death and new admission for heart failure. A prognostic index was obtained from the ambulatory blood pressure monitoring variables according to the formula: (220-age)-mean 24 h heart rate (m24hHR)+mean 24 h diastolic blood pressure (m24hDBP). RESULTS: Among many potential predictors only left-ventricular ejection fraction, creatinine levels, Killip class and the prognostic index were independently associated with events during the follow-up. In particular, higher values of the prognostic index were associated with a lower incidence of events, with an odds ratio of 0.958 (95% confidence intervals 0.943 0.974) and a 4% reduction in risk for each point of the prognostic index. Overall incidence of cardiac events was 6-fold higher in patients within the lowest quartile of the prognostic index (< or =148) compared with the other three quartiles (12 vs. 2, 1.4 and 2% respectively in the other three quartiles; P<0.0001). CONCLUSIONS: A simple prognostic index based on ambulatory blood pressure monitoring and age may be a useful tool in predicting cardiac death and heart failure in patients with recent myocardial infarction. PMID- 17353649 TI - US demographic trends in mid-arm circumference and recommended blood pressure cuffs for children and adolescents: data from the National Health and Nutrition Examination Survey 1988-2004. AB - OBJECTIVE: Mid-arm circumference measurement is a prerequisite for the selection of properly sized blood pressure cuffs for accurate blood pressure readings in children and youth. This study examined recent trends in the mid-arm circumference distribution and the distribution of corresponding recommended blood pressure cuff sizes using National Health and Nutrition Examination Survey III (1998-1994) and National Health and Nutrition Examination Survey 1999-2004 data. DESIGN: Both studies were complex, cross-sectional surveys providing nationally representative samples of the civilian noninstitutionalized US population. PARTICIPANTS: Children of 7-17 years of age were studied. A total of 2515 boys and 2596 girls participated in National Health and Nutrition Examination Survey III, and 3941 boys and 3917 girls in National Health and Nutrition Examination Survey 1999-2004. STATISTICAL ANALYSIS: Mean mid-arm circumference and recommended National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents defined blood pressure cuff sizes were assessed by sex, age, and race/ethnicity. US boys aged 7 12 years and girls aged 7-12 and 13-17 years had significant increases in mid-arm circumference (P<0.05) across the two surveys. Moreover, from 1988-1994 to 1999 2004, there were statistically significant increases in the percentage of boys (age 7-12 and 13-17 years) and girls (age 13-17 years) needing large blood pressure adult cuffs (P<0.05). National Health and Nutrition Examination Survey 1999-2004 data show that both boys and girls aged 13-17 years had a mean mid-arm circumference > or =27 cm, which requires an adult blood pressure cuff fit. Furthermore, 52% boys and 42% girls aged 13-17 years, required a standard adult cuff fit. CONCLUSION: Mean mid-arm circumference has increased among US children and adolescents, with important implications for the accuracy of blood pressure measurement in clinical practice. PMID- 17353650 TI - Blood pressure assessment during resistance exercise: comparison between auscultation and Finapres. AB - OBJECTIVES: The objective of this study was to test whether the auscultatory method and Finapres provide similar readings for blood pressure response during two resistance exercise protocols of different intensities, and to gain some insight into whether auscultation can be used to monitor cardiovascular stress during resistance exercise. METHODS: Fourteen patients performed six and 15 maximum repetitions (six and 15, respectively) of one-leg knee extension on different days. Blood pressure (BP) was measured simultaneously with the two methods at rest and during the last repetition of the protocols. RESULTS: Neither the systolic blood pressure (SBP) nor the diastolic blood pressure (DBP) differed between methods, both at rest and at six maximum repetitions. Conversely, Finapres recorded higher systolic blood pressure at 15 maximum repetitions (168.8+/-21.7 mmHg) than auscultation (147.0+/-14.5 mmHg; P<0.001). In addition, the blood pressure values obtained by both methods in each exercise protocol (six and 15 maximum repetitions, respectively) were ranked in tertiles and also treated by the gamma (gamma) nonparametric correlation. We observed a high probability for patients to be ranked on the same tertile regardless of the method used, at both six maximum repetitions (SBP=0.80, DBP=0.97) and 15 maximum repetitions (SBP=0.88, DBP=0.92). High association between methods was also observed by simple regression when measurements taken at rest and at each intensity were analyzed altogether for both SBP (r=0.95, r adjusted=0.89) and DBP (r=0.79, r adjusted=0.62). CONCLUSION: Auscultation provides lower BP values than Finapres, especially at the end of a set including 15 maximum repetitions. The former, however, seems appropriate to assess the relative cardiovascular stress imposed by different protocols of resistance exercise. PMID- 17353651 TI - Left ventricular (LV) geometry and dipping state are determinants of LV mass reduction with angiotensin-converting enzyme inhibitor antihypertensive treatment. AB - OBJECTIVES: Left ventricular hypertrophy is a major risk predictor in hypertensive patients and its regression is beneficial in terms of prognosis. The aim of this observational, open-labeled study was to investigate the effect of left ventricular geometry and dipping pattern on left ventricular mass reduction after chronic treatment with angiotensin-converting enzyme inhibitors, in a large population of hypertensive patients. METHODS: We evaluated untreated patients with mild to moderate essential hypertension, before and 6 months after treatment with angiotensin-converting enzyme inhibitor monotherapy or angiotensin converting enzyme inhibitor-low-dose thiazide combination. Left ventricular mass index, relative wall thickness and geometry pattern were derived from echocardiography. Dipping state was determined with 24-h ambulatory blood pressure monitoring at enrollment. RESULTS: Overall, left ventricular mass index decrease in the 1400 patients (mean age 52.5 years) who completed the study was 12.9% of baseline value (P<0.00001). After adjusting for pretreatment value, left ventricular mass index reduction was similar with all angiotensin-converting enzyme inhibitors used [P= NS (not significant)], but it was higher in nondippers than dippers (14.1 vs. 12.3%, P<0.0001) and in patients with than without baseline left ventricular hypertrophy (14.6 vs. 11.3%, P<0.0001). We observed a stepwise augmentation of left ventricular mass index decrease with worsening left ventricular geometry (P<0.001). In multivariable analysis, impaired left ventricular geometry and blunted nocturnal blood pressure fall before treatment were independent predictors of a high left ventricular mass index reduction after treatment, independent of blood pressure fall, pretreatment left ventricular mass index, and other potential confounders. CONCLUSION: In essential hypertension, left ventricular geometry and dipping state are independent determinants of left ventricular mass reduction with angiotensin-converting enzyme inhibitor treatment. All angiotensin-converting enzyme inhibitors are efficient in decreasing left ventricular mass. PMID- 17353652 TI - Lack of association between body-mass index and white-coat hypertension among referred patients. AB - OBJECTIVE: The association between body-mass index and ambulatory blood pressure variables is not straightforward. Specifically, there are contradicting data regarding the correlation between obesity and white-coat hypertension. The aim of this report was to study the relationship between body-mass index and the white coat effect, defined by ambulatory monitoring. METHODS: A retrospective analysis of a prospectively collected ambulatory blood pressure monitoring laboratory database was performed. We analyzed 3928 unselected ambulatory monitoring sessions of nontreated (n=1654) and treated (n=2274) patients, for statistical associations between body-mass index and blood pressure variables. Body-mass index was categorized according to National Institutes of Health classification or quartiles. RESULTS: Office and ambulatory blood pressure variables correlated with body-mass index in untreated patients. Unadjusted, the systolic white-coat effect did not differ by body-mass index category, whereas the diastolic effect was higher in obese patients. Adjustment for age, sex and office blood pressure revealed inverse associations of body-mass index category with the systolic white coat effect, in both untreated and treated patients. When determined categorically, neither overweight/obese untreated or treated patients had increased prevalence of white-coat hypertension. Multivariate linear regression models confirmed the negative correlation between body-mass index and the systolic white-coat effect in untreated (beta=-0.24, P<0.0001) and treated (beta= 0.14, P<0.05) patients. CONCLUSION: In patients referred for ambulatory blood pressure monitoring there was no association between body-mass index and white coat hypertension. PMID- 17353653 TI - Reproducibility of dipping/nondipping pattern in untreated essential hypertensive patients: impact of sex and age. AB - OBJECTIVE: We aimed to evaluate the intrasubject short-term reproducibility of nocturnal blood pressure patterns (dipping/nondipping) in essential hypertensive patients in relation to age (<50 and > or =50 years) and sex. METHODS: A total of 619 never-treated essential grade 1 and 2 hypertensive patients (383 men, 236 women) underwent the following procedures: (1) repeated clinic blood pressure measurements, (2) routine examinations, (3) ambulatory blood pressure monitoring over two 24-h periods within 4 weeks. Dipping pattern was defined as a 10%, or more, reduction in average systolic blood pressure/ diastolic blood pressure at night compared to daytime values. RESULTS: Of the 407 patients showing a dipping pattern during the first ambulatory blood pressure monitoring period, 329 (80.1%) had the same pattern during the second ambulatory blood pressure monitoring recording. Of the 212 patients with a nondipping pattern during the first ambulatory blood pressure monitoring period, 140 (65.9%) confirmed the same pattern during the second ambulatory blood pressure monitoring period. Overall, 149 patients (24.1%) changed their initial nocturnal pattern at the second ambulatory blood pressure monitoring recording, without significant age and sex related differences. Lower reproducibility rates of the nondipping as compared to the dipping pattern were found in the whole population as well as in men regardless of age and in younger but not in older women. CONCLUSIONS: These findings indicate that nocturnal blood pressure patterns have a limited short term reproducibility in the whole study population as well as in different age and sex subgroups. As variability of nocturnal blood pressure patterns is not predicted by easy available clinical data, such as sex and age, a reliable classification of patients according to circadian blood pressure patterns should be obtained by repeating ambulatory blood pressure monitoring. PMID- 17353654 TI - The Health and Life device (HL888HA): accuracy assessment in an adult population according to the British Hypertension Society protocol. AB - OBJECTIVE: Over the last two decades, concerns over mercury toxicity have given rise to the continuous release of new and improved automated blood pressure measurement devices as a replacement for the mercury sphygmomanometer. Out-of office blood pressure monitoring has been shown to have various advantages, including a reduced white-coat effect and observer error, as well as better prediction of cardiovascular risk/complications. We assessed the accuracy of the Health and Life device (HL888HA) (Health and Life Co. Ltd., Taipei, Taiwan) in an adult population according to the British Hypertension Society protocol. METHODS: Local ethics committee approval was obtained and participants were recruited from a large teaching hospital. Nine blood pressure measurements were taken from each participant, alternating between a mercury sphygmomanometer and the test device. Data from 85 participants who fulfilled the British Hypertension Society criteria were analysed according to the protocol guidelines. RESULTS: The device achieved the highest possible grade (A/A) according to the British Hypertension Society protocol. The mean difference and SD of 0.5 (7.3) mmHg for systolic and -2.1 (7.8) mmHg for diastolic pressure, which complies with the standard of the American Association for the Advancement of Medical Instrumentation. CONCLUSION: The Health and Life device (HL888HA) can be recommended for use in an adult population according to the criteria of the British Hypertension Society protocol. PMID- 17353655 TI - Validation of the Oscar 2 oscillometric 24-h ambulatory blood pressure monitor according to the British Hypertension Society protocol. AB - OBJECTIVES: Accuracy of blood pressure measuring devices is of prime importance and should be validated before devices are used clinically. We carried out an independent evaluation of the Oscar 2 oscillometric ambulatory blood pressure monitor (SunTech Medical, Model 222) according to the British Hypertension Society (BHS) Protocol. METHODS: Validation of the Oscar 2 was carried out in accordance with Part 1 of the British Hypertension Society protocol. Having successfully completed the first three phases, in the static validation phase blood pressure measurements were made on 114 participants simultaneously by two observers blinded from each other's readings and those of the device, giving 255 data pairs for systolic and diastolic blood pressure. Readings were made using simultaneous same-arm measurement, each observer using a dual-head binaural stethoscope and a calibrated mercury sphygmomanometer. Data were recorded independently, to the nearest 2 mmHg and were checked by the supervisor who operated the device. RESULTS: The device mean and observer means (and standard deviations) were exceptionally close across a high range of pressures, with a mean difference for the better observer of 0+/-7 mmHg and -1+/-6 mmHg for systolic and diastolic blood pressure, respectively. With 62% of all systolic blood pressure standard vs. device differences equal or less than 5 mmHg, and 70% of all similar differences for diastolic blood pressure equal to or less than 5 mmHg, the device was categorized as Grade A for systolic and diastolic blood pressure. CONCLUSION: The Oscar 2 was graded A for both systolic and diastolic blood pressure by the British Hypertension Society protocol and can be recommended for clinical use in an adult population. PMID- 17353656 TI - Validation of the Samsung SBM-100A and Microlife BP 3BU1-5 wrist blood pressure measuring devices in adults according to the International Protocol. AB - OBJECTIVE: A variety of automatic blood measurement devices with diverse features have been introduced to the medical markets recently. Among these devices, models that measure at the wrist have become increasingly popular in self measurements. The objective of this study was to evaluate the accuracy of the Samsung SBM-100A and Microlife BP 3BU1-5 wrist blood pressure devices against the mercury sphygmomanometer in adults according to the International Protocol criteria. METHODS: Fifty-four patients over 30 years of age were studied and classified based on the International Protocol range. Blood pressure measurements at the wrist with the Samsung SBM-100A and Microlife BP 3BU1-5 were compared with the results obtained by two trained observers using a mercury sphygmomanometer. Nine sequential blood pressure measurements were taken. A total of 33 participants with randomly distributed arm circumferences were selected for both of the validation studies. During each validation study, 99 measurements were obtained for comparison from 33 participants. The first phase was performed on 15 participants and if the device passed this phase, 18 more participants were selected. RESULTS: Mean discrepancies and standard deviations of the device sphygmomanometer were 0.9+/-9.2 and -2.7+/-9.3 mmHg for systolic blood pressure and -1.4+/-8.0 mmHg and 1.4+/-5.7 for diastolic blood pressure in the Samsung and Microlife study groups, respectively. The Samsung SBM-100A passed Phase 1 in 15 participants. Despite the fact that Microlife BP 3BU1-5 passed Phase 1 for diastolic pressure, it failed according to the systolic pressure criteria. Eighteen patients were added and Phase 2 was continued, in which Samsung SBM-100A failed to meet the criteria of Phases 2.1 and 2.2 for adults in systolic and diastolic blood pressure. It was found that the Microlife BP 3BU1-5 does not meet the criteria of either of Phases 2.1 and 2.2 for systolic blood pressure and Phase 2.2 for diastolic blood pressure. CONCLUSION: In this study, Samsung SBM 100A and Microlife blood pressure 3BU1-5 wrist blood pressure monitoring devices were found to be incompetent to meet the criteria of the International Protocol and it has not been possible to suggest any one of them for clinical use in adults. PMID- 17353657 TI - A tool for reliable self-home blood pressure monitoring designed according to the European Society of Hypertension recommendations: the Microlife WatchBP Home monitor. AB - BACKGROUND: Self-blood pressure monitoring by patients at home (HBPM) is being increasingly used in clinical practice and has been endorsed by hypertension societies as an important adjunct to the conventional office blood pressure measurements. Several problems, however, exist regarding the application of HBPM in practice, such as device inaccuracy, observer bias and misreporting, variable monitoring schedule and variable method for summarizing measurements. The European Society of Hypertension Working Group (ESH-WG) on Blood Pressure Monitoring has published detailed recommendations on how to apply HBPM in clinical practice. OBJECTIVE: The Microlife WatchBP Home monitor is designed to provide reliable and unbiased self-blood pressure monitoring by patients at home, strictly according to the ESH-WG recommendations. DESIGN: Dual-function automated oscillometric monitor for HBPM in the arm, with memory, PC link capacity and embedded monitoring schedule. The device has a Usual mode for casual HBPM and a Diag (diagnostic) mode for HBPM strictly according to the ESH-WG proposed schedule (duplicate morning and evening measurements for 7 days). Readings are averaged by the device after exclusion of the initial day according to ESH-WG recommendations and can be transferred to PC for storing or printing. A pilot study in hypertensive patients with previous experience in HBPM suggested that the device is user-friendly and well accepted. CONCLUSION: The Microlife WatchBP Home monitor is a novel device that provides a reliable and unbiased assessment of home blood pressure strictly according to the ESH recommendations. PMID- 17353659 TI - Membrane lipids as signaling molecules. AB - PURPOSE OF REVIEW: Membrane lipids play important roles in signaling reactions. They are involved in most if not all cellular signaling cascades and in a wide variety of tissue and cell types. The purpose of this review is to highlight major pathways of signaling originating in membrane lipids. Details of lipid metabolism, and its relation to protein function, will thus advance understanding of the role of lipids in health and disease. RECENT FINDINGS: Major classes of lipids including glycerophospholipids, their metabolites (eicosanoids, endocannabinoids), and sphingolipids have recently generated interest in the field of signal transduction. These lipids are tightly regulated and have an impact on various physiological functions. Importantly, aberrant lipid metabolism often leads to onset of pathology, and thus the precise balance of signaling lipids and their effectors can serve as biomarkers. SUMMARY: Membrane lipids form precursors for second messengers and functional assembly matrices on membrane domains during cellular stimulation. Many of these modifications are rapid reactions at lipid headgroups. Metabolism of the fatty acyl portion of membrane lipids leads to the generation of a bewildering complexity of lipid mediators with extended effects in space and time. PMID- 17353660 TI - Endocannabinoids and the regulation of their levels in health and disease. AB - PURPOSE OF REVIEW: Endocannabinoids are defined as endogenous agonists of cannabinoid receptors, that is, of the two G-protein-coupled receptors for the Cannabis psychoactive principle Delta-tetra-hydrocannabinol. Two such endogenous mediators have been most thoroughly studied so far: anandamide and 2 arachidonoylglycerol. Here we review the mechanisms for the regulation of their levels under physiological and pathological conditions, and recent findings on their role in disease. RECENT FINDINGS: It is becoming increasingly clear that, although both anandamide and 2-arachidonoyl-glycerol are produced and degraded 'on demand', the levels of these two compounds appear to be regulated in different, and sometimes even opposing, ways, often using redundant molecular mechanisms. Alterations of endocannabinoid levels have been found in both animal models of pain, neurological and neurodegenerative states, gastrointestinal disorders and inflammatory conditions, and in blood, cerebrospinal fluid and bioptic samples from patients with various diseases. SUMMARY: Endocannabinoid levels appear to be transiently elevated as an adaptive reaction to re-establish normal homeostasis when this is acutely and pathologically perturbed. In some chronic conditions, however, this system also contributes to the progress or symptoms of the disorder. As a consequence, new therapeutic drugs are being designed from both stimulants and blockers of endocannabinoid action. PMID- 17353661 TI - The orphan nuclear receptor Rev-erbalpha: a transcriptional link between circadian rhythmicity and cardiometabolic disease. AB - PURPOSE OF REVIEW: This review focuses on recent advances on the role of the orphan nuclear receptor Rev-erbalpha, a transcription factor participating in the control of circadian rhythm and cardiometabolic disease. RECENT FINDINGS: Circadian patterns of cardiovascular vulnerability are well documented, with a peak incidence of cardiovascular events in the morning. Recent studies have outlined the importance of the Clock genes in the development of metabolic disorders predisposing to atherosclerosis. Rev-erbalpha is a nuclear receptor that regulates hepatic and adipose lipid metabolism as well as vascular inflammation. Moreover, Rev-erbalpha is also part of the clock transcription machinery and the target of some clock transcription factors. SUMMARY: These findings identify Rev-erbalpha as a modulator of cardiovascular risk factors and as a determinant of the circadian regulation of metabolic pathways. Moreover, Rev erbalpha crosstalks with other nuclear receptors which influence atherosclerosis susceptibility. Rev-erbalpha may thus serve to integrate metabolic and circadian signals. PMID- 17353662 TI - HDL cholesterol transport during inflammation. AB - PURPOSE OF REVIEW: The aim of this article is to review recent advances made towards understanding how inflammation and acute phase proteins, particularly serum amyloid A and group IIa secretory phospholipase A2, may alter reverse cholesterol transport by HDL during inflammation and the acute phase response. RECENT FINDINGS: Findings suggest that the decreased apoA-I content and markedly increased serum amyloid A content in HDL during the acute phase response result from reciprocal and coordinate transcriptional regulation of these proteins as well as HDL remodeling by group IIa secretory phospholipase A2. Serum amyloid A functions efficiently in a lipid-free or lipid-poor form to promote cholesterol efflux by ATP binding cassette protein ABCA1, evidently by functioning directly as an acceptor for cholesterol efflux as well as by increasing the availability of cellular free cholesterol. Serum amyloid A increases the ability of acute phase HDL to serve as an acceptor for SR-BI-dependent cellular cholesterol efflux. Altered remodeling of HDL by group IIa secretory phospholipase A2 in concert with cholesterol ester transfer protein may contribute to the generation of lipid-poor apoA-I and serum amyloid A acceptors for cholesterol efflux. SUMMARY: Current data support a model for the acute phase response in which serum amyloid A and sPLA2-IIa, present at sites of inflammation and tissue damage, play a protective role by enhancing cellular cholesterol efflux, thereby promoting the removal of excess cholesterol from macrophages. PMID- 17353663 TI - The role of perilipin in human obesity and insulin resistance. AB - PURPOSE OF REVIEW: More than 1.1 billion people worldwide are overweight or obese. We know that obesity is determined by a combination of environmental and genetic factors. Although hundreds of obesity candidate genes have been identified through different metabolic pathways, the fundamental basis of obesity resides with excessive storage of triacylglycerides in adipose tissue. RECENT FINDINGS: The mechanisms that control the storage and release of triacylglycerides in lipid droplets are complex and poorly understood; yet, they are likely to be crucial to the understanding of the regulation of body weight. In this regard, the family of perilipin, adipophilin and TIP47 proteins may play key roles in obesity. It has recently been shown that variants at the perilipin locus were associated with BMI and obesity risk in females from several population studies. Moreover, the reported interactions between perilipin and dietary factors may shed light on the complex relation between dietary intake and body weight changes observed on an individual basis. SUMMARY: These findings support an important role for PLIN as a candidate gene for obesity risk in humans as well as a modulator of dietary response to therapies aimed to reduce body weight and decrease metabolic syndrome risk. PMID- 17353664 TI - Genetic factors affecting HDL levels, structure, metabolism and function. AB - PURPOSE OF REVIEW: HDL is a recognized negative risk factor for the cardiovascular diseases. Establishing the genetic determinants of HDL concentration and functions would add to the prediction of cardiovascular risk and point to the biochemical mechanisms underlying this risk. The present review focuses on various approaches to establish genetic determinants of the HDL concentration, structure and function. RECENT FINDINGS: While many genes contribute to the HDL concentration and collectively account for half of the variability, polymorphism of individual candidate genes contributes little. There are strong interactions between environmental and genetic influences. Recent findings have confirmed that APOA1 and ABCA1 exert the strongest influence on HDL concentrations and risk of atherosclerosis. CETP and lipases also affect the HDL concentration and functionality, but their connection to the atherosclerosis risk is conditional on the interaction between environmental and genetic factors. SUMMARY: Analysis of genetic determinants of HDL-cholesterol in patients with specific disease states or in response to the environmental condition may be a more accurate way to assess variations in HDL concentration. This may result in defining the rules of interaction between genetic and environmental factors and lead to understanding the mechanisms responsible for the variations in HDL concentration and functionality. PMID- 17353665 TI - Pharmacogenetics and pharmacogenomics of cholesterol-lowering therapy. AB - PURPOSE OF REVIEW: To summarize recent findings on pharmacokinetics, pharmacodynamics, drug-drug interactions and influence of lifestyle heterogeneity on adverse events in cholesterol-lowering therapy RECENT FINDINGS: The prevention of cardiovascular disease is critically dependent on lipid-lowery therapy, including statins, cholesterol absorption inhibitors, fibrates and nicotinic acid. Statins are the most prescribed drugs in lipid lowering therapy with variability in response and almost one third of the patients do not meet their treatment goals. The severe adverse effects of treatment with cerivastatin stimulated the search for new genes and gene variations affecting pharmacokinetics, drug-drug interactions and pharmacodynamics. Moreover, instead of monotherapy, combined therapy of statins with ezetemibe and niacin was considered. This led to the identification of CD13, NPC1L1 and HM74A as new targets and CYP2C8 and glucuronidation enzymes as potential targets for drug-drug interactions. Moreover multiple polymorphic sites and pleiotrophic gene targets were reinvestigated in larger cohorts and the relevant pathogenetic factors start to evolve. SUMMARY: Statin therapy is widely used and well tolerated by the majority of patients. To further reduce potential adverse effects and to increase efficacy, combined therapy concepts with ezetimibe or niacin are underway. PMID- 17353666 TI - Genomic copy number variation and its potential role in lipoprotein and metabolic phenotypes. AB - PURPOSE OF REVIEW: This review examines the role of copy number variation in the human genome as a newly recognized determinant of lipoprotein and metabolic phenotypes. RECENT FINDINGS: Much of the recent progress defining the molecular basis of lipoprotein disorders has been the result of studying genomic DNA at the single nucleotide level, for instance with nucleotide sequence analysis or genotyping to detect single nucleotide polymorphisms. Focus on single nucleotides, however, fails to capture the complete spectrum of potential genetic variability. Recent genome-wide mapping studies have demonstrated the surprising ubiquity of large-scale copy number variations in apparently healthy people, adding to the complexity of the 'normal' genome, but also emphasizing this form of genetic variation as a potential disease mechanism. The application of this understanding to the genetics of lipoprotein disorders has been rapid. For instance, the use of novel techniques to detect copy number variations, such as multiplex ligation-dependent probe amplification, has revealed many additional causative mutations in the low-density lipoprotein receptor gene in patients with familial hypercholesterolemia. SUMMARY: Copy number variations thus represent a new level of genomic variation that is both an important mechanism of monogenic lipoprotein disorders and a potential contributor to common complex lipoprotein and metabolic phenotypes in the general population. PMID- 17353667 TI - Biomarker discovery using high-dimensional lipid analysis. AB - PURPOSE OF REVIEW: High-dimensional lipid analysis technologies (lipidomics) provide researchers with an opportunity to measure lipids on an unprecedented scale. They do not, however, guarantee a fast track to new knowledge. The vast amount of data produced by these platforms presents a major hurdle to assembling valid knowledge and to the discovery of mechanistic biomarkers. This review examines strategies for improving the quality of high-dimensional lipid data and streamlining data analysis to increase the value of lipidomics platforms to research and commercial applications. RECENT FINDINGS: Recent articles focus on careful study design and data analysis protocols. Authors offer detailed descriptions of study populations, analytical methods and data analysis, and highlight the use of practical data preprocessing and the incorporation of biological knowledge into data analysis. SUMMARY: The field is moving towards more methodical and structured approaches to biomarker identification. Experimental designs focusing on well-defined outcomes have a better chance of producing biologically relevant results. The high-dimensional lipid analysis techniques available are varied, have different strengths and weaknesses, and must be chosen carefully depending on the experimental design and application. Many techniques for data analysis are available, but the most successful are those incorporating existing biological knowledge into the statistical analysis. PMID- 17353668 TI - Identification of differentially expressed genes and false discovery rate in microarray studies. AB - PURPOSE OF REVIEW: To highlight the development in microarray data analysis for the identification of differentially expressed genes, particularly via control of false discovery rate. RECENT FINDINGS: The emergence of high-throughput technology such as microarrays raises two fundamental statistical issues: multiplicity and sensitivity. We focus on the biological problem of identifying differentially expressed genes. First, multiplicity arises due to testing tens of thousands of hypotheses, rendering the standard P value meaningless. Second, known optimal single-test procedures such as the t-test perform poorly in the context of highly multiple tests. The standard approach of dealing with multiplicity is too conservative in the microarray context. The false discovery rate concept is fast becoming the key statistical assessment tool replacing the P value. We review the false discovery rate approach and argue that it is more sensible for microarray data. We also discuss some methods to take into account additional information from the microarrays to improve the false discovery rate. SUMMARY: There is growing consensus on how to analyse microarray data using the false discovery rate framework in place of the classical P value. Further research is needed on the preprocessing of the raw data, such as the normalization step and filtering, and on finding the most sensitive test procedure. PMID- 17353670 TI - Bibliography. Current world literature. Genetics and molecular biology. PMID- 17353669 TI - Functional analysis of regulatory single-nucleotide polymorphisms. AB - PURPOSE OF REVIEW: The identification of regulatory polymorphisms has become a key problem in human genetics. In the past few years there has been a conceptual change in the way in which regulatory single-nucleotide polymorphisms are studied. We revise the new approaches and discuss how gene expression studies can contribute to a better knowledge of the genetics of common diseases. RECENT FINDINGS: New techniques for the association of single-nucleotide polymorphisms with changes in gene expression have been recently developed. This, together with a more comprehensive use of the old in-vitro methods, has produced a great amount of genetic information. When added to current databases, it will help to design better tools for the detection of regulatory single-nucleotide polymorphisms. SUMMARY: The identification of functional regulatory single-nucleotide polymorphisms cannot be done by the simple inspection of DNA sequence. In-vivo techniques, based on primer-extension, and the more recently developed 'haploChIP' allow the association of gene variants to changes in gene expression. Gene expression analysis by conventional in-vitro techniques is the only way to identify the functional consequences of regulatory single-nucleotide polymorphisms. The amount of information produced in the last few years will help to refine the tools for the future analysis of regulatory gene variants. PMID- 17353671 TI - Feeding baby: consequences of over-nutrition in utero. PMID- 17353672 TI - Proprotein convertase subtilisin/kexin type 9, its variants and regulation of low density lipoprotein cholesterol. PMID- 17353673 TI - Hyperlipidemia and cardiovascular disease. PMID- 17353674 TI - Therapy and clinic trials. PMID- 17353676 TI - Uterine artery Doppler in the prediction of adverse pregnancy outcome. AB - PURPOSE OF REVIEW: To review publications, published during the past year, that have examined uterine artery Doppler findings in women with adverse pregnancy outcome. RECENT FINDINGS: Almost two-thirds of stillbirths that occur in the early preterm period (up to 32 weeks) can be predicted by uterine artery Doppler at 23 weeks. First trimester screening studies have shown that an abnormal result increases the risk of subsequent fetal growth restriction, and such women are at particularly high risk when indices remain abnormal in the second trimester. Studies combining uterine artery Doppler with maternal serum markers have demonstrated that measurement of first-trimester maternal serum pregnancy associated plasma protein A and free beta human chorionic gonadotrophin improve sensitivities of second-trimester Doppler. As these are frequently measured in Down syndrome screening and they lend themselves in screening for pre-eclampsia. Women with abnormal first and second-trimester serum markers constitute a high risk group. Maternal serum placental protein 13 remains a promising method for early screening, although a recent study suggests lower sensitivities than initially reported. SUMMARY: Uterine artery Doppler screening identifies women at high risk for developing adverse pregnancy outcomes. Detection rates may be increased and false positive rates reduced by combination with maternal characteristics or serum markers. PMID- 17353677 TI - Increased risk in the elderly parturient. AB - PURPOSE OF REVIEW: The steady increase in age in primiparous and multiparous women raises questions concerning increased obstetric risk and outcome in such pregnancies. This review highlights the effects of maternal age on obstetric and perinatal outcome. RECENT FINDINGS: Complications have been associated with increasing maternal age, including abnormal weight gain, obesity, gestational diabetes, chronic and pregnancy-induced hypertension, antepartum haemorrhage, placenta praevia, multiple gestation, prelabour rupture of membranes, and preterm labour. Intrapartum complications of malpresentation, fetopelvic disproportion, abnormal labour, increased use of oxytocin in labour, caesarean section, instrumental delivery, sphincter rupture, and postpartum haemorrhage are more frequent in older women. Advanced maternal age is associated with a higher risk of stillbirth throughout gestation, and the peak risk period is 37-41 weeks. Perinatal outcomes differ with maternal age concerning gestational age, birth weight, prematurity, low birth weight, incidence of small-for-gestational-age infants, fetal distress, and perinatal morbidity and mortality. The increased risk cannot be explained only by intercurrent illness or pregnancy complications. SUMMARY: Increasing maternal age is independently associated with specific adverse outcomes. Increasing age is a continuum rather than threshold effect. More information about obstetric consequences of delayed childbearing is needed both for obstetricians and fertile women. PMID- 17353678 TI - Reproductive outcomes after in-vitro fertilization. AB - PURPOSE OF REVIEW: This paper reviews the effect of in-vitro fertilization on maternal and perinatal outcomes of pregnancy. RECENT FINDINGS: Few randomized, controlled trials have been published in this area due to inherent difficulties in studying this population of infertile women who require in-vitro fertilization. Systematic review of the literature identified published studies that consistently highlighted the higher incidence of maternal and perinatal morbidity associated with pregnancies following in-vitro fertilization. SUMMARY: Some prospective observational studies compare maternal and perinatal outcomes in in-vitro fertilization pregnancies. Larger studies show that adverse pregnancy outcomes such as preeclampsia, gestational hypertension, placental abruption, placenta praevia, and preterm delivery increase significantly with in-vitro fertilization. Perinatal adverse outcomes such as prematurity and those related to plurality of the pregnancy also increase. All patients undergoing in-vitro fertilization should have careful counselling regarding these increased risks prior to treatment. PMID- 17353679 TI - Viral respiratory disease in pregnancy. AB - PURPOSE OF REVIEW: Recently there has been an increased concern over viral respiratory infections and their potential for a pandemic. This concern makes it important to review the most current guidelines for the management of viral respiratory diseases in pregnancy. RECENT FINDINGS: The topics covered are influenza, avian influenza, and severe acute respiratory syndrome. SUMMARY: Pregnant women have an increased susceptibility to viral respiratory diseases. The most common respiratory virus to infect pregnant women is influenza. All women who intend to become pregnant or are pregnant should receive the influenza vaccine. If a pregnant woman develops influenza she should be treated with supportive care. Antiviral medications should be reserved for cases where the benefits outweigh the risks. Avian influenza (H5N1) is a new emerging virus usually contracted from direct contact with diseased birds. There is no commercially available vaccine at this time to prevent infection. Pregnant women should be treated aggressively with supportive care and antiviral medications, as the significant risk of maternal mortality outweighs the potential fetal risks. Pregnant women diagnosed clinically with severe acute respiratory syndrome should be treated empirically, as a serologic diagnosis can take weeks to confirm. The treatment of pregnant women with severe acute respiratory syndrome should be without ribavirin. PMID- 17353680 TI - Psychosomatic disorders in pregnancy. AB - PURPOSE OF REVIEW: Common and important psychosomatic disorders in pregnancy reviewed here include perinatal depression, posttraumatic stress disorders, anxiety disorders, eating disorders, and postpartum psychosis. RECENT FINDINGS: Research has focused on antenatal depression as postpartum depression often has onset prior to delivery. Certain psychosocial and psychological interventions can effectively prevent postnatal depression. Although the use of selective serotonin reuptake inhibitors was associated with miscarriage, preterm delivery, and fetal death, discontinuation of antidepressants also increased the relapse rate during pregnancy. Studies also show that about 8% of mothers had eating problems during their pregnancy, which increased to 19% in the postpartum period. Postpartum psychosis is an important diagnosis related to maternal death from suicide. Personal and family history of bipolar disorders are important risk factors. SUMMARY: Recent findings highlight the importance of correct diagnosis and awareness of serious mental illness. In view of the higher rate of relapse, women should be counselled carefully regarding discontinuation of antidepressants during pregnancy. Differentiation of posttraumatic stress disorders with comorbid anxiety and depression, awareness of risk factors, and clinical features of psychosis are important in the management of psychosomatic disorders in pregnancy. PMID- 17353681 TI - Symphysial pelvic dysfunction. AB - PURPOSE OF REVIEW: Symphysial pelvic dysfunction is a condition which develops during pregnancy and may lead to significant morbidity affecting quality of life. While postpartum resolution is common, symptoms may persist for many years. The consequences, specifically disabling pain, are even more detrimental on mothers with a young family. This review summarizes current understanding of the condition, including pathogenesis, risk factors and management. RECENT FINDINGS: There is no current international consensus on definition, diagnostic criteria, and treatment protocols for symphysial pelvic dysfunction. Discrepancy between the reported rates of prevalence stems from ambiguity in definition and inclusion criteria in reported studies. The pathogenesis of the condition is still unclear although numerous theories have been proposed. It is likely to be multifactorial in origin with multiple factors both biomechanical and genetic factors playing an important role. There is also a paucity of information in the literature about the best management strategy. SUMMARY: There is an urgent need to standardize terminology and define diagnostic criteria for symphysial pelvic dysfunction in order to improve the management and better understand the pathophysiology of this condition. PMID- 17353682 TI - Gynaecological malignancies in pregnancy. AB - PURPOSE OF REVIEW: To review the management of gynaecological cancers occurring in association with pregnancy. To consider the impact of the cancer on the pregnancy, and the impact of the pregnancy on the cancer. RECENT FINDINGS: The management of gynaecological cancers in pregnancy remains, fortunately, a rare problem for the gynaecological oncology team. This inevitably means that many management decisions will be informed by relatively small case series and case reports. There have been interesting reports where pregnancy has been prolonged to achieve fetal viability in both cervix and ovary cancer in pregnancy, and these are discussed below. SUMMARY: Any cancer in pregnancy is a catastrophic event for the woman and her partner, and poses great challenges for the multidisciplinary team responsible for her care. Gynaecological cancers in pregnancy are even more stressful as the woman will naturally worry about the survival of her baby, and the implications for her future fertility. Fortunately the outcome for most women and their babies is favourable. PMID- 17353683 TI - Near miss audit in obstetrics. AB - PURPOSE OF REVIEW: Over the past decade, there has been increasing interest internationally in studying maternal near misses, or severe morbidity, to complement traditional audit of maternal mortality. This review summarizes studies in this field published during 2005-2006. RECENT FINDINGS: There is wide variation among published studies in terms of definitions of near miss, sources of data, and assessment of quality of care. Some investigators focus on single categories of near miss (e.g. postpartum haemorrhage, obstetric hysterectomy, intensive care unit admission), whereas others include multiple categories (ranging from two to 14). Some groups identify cases from routinely collected administrative data; whereas others search hospital registers and individual case records. Many investigators make no attempt to assess quality of care or preventability, but restrict their studies to the reporting of rates of severe morbidity. Others assess care by means of interviews with survivors or case note review, but study only a sample of cases and cannot report incidence rates. A minority of investigators both report incidence rates and assess quality of care. SUMMARY: Near miss audit is increasingly used to complement maternal mortality review. Standardization of inclusion criteria and of methods for case assessment would facilitate comparisons over time and among countries. PMID- 17353684 TI - Fetal magnetic resonance imaging: a review. AB - PURPOSE OF REVIEW: To describe advances in magnetic resonance technology and the current indications and advantages of magnetic resonance imaging that have led to increased utilization in fetal medicine. RECENT FINDINGS: The article covers the most common uses of magnetic resonance imaging in fetal medicine. The advantages of magnetic resonance imaging for the diagnosis of fetal malformations are described, in particular the advantages of magnetic resonance imaging in central nervous system malformations not optimally diagnosed by ultrasound are described. These cases include malformations of migration, malformations of development, such as agenesis of the corpus callosum, and destructive lesions. Noncentral nervous system lesions include chest abnormalities, abdominal wall defects, gastrointestinal and genitourinary abnormalities and fetal neoplasms. Abnormalities of placentation and other maternal factors affecting pregnancy are shown. SUMMARY: Recent studies have shown that magnetic resonance imaging can add significantly to the prenatal diagnosis and management of congenital abnormalities. In addition, placental abnormalities have been diagnosed with greater accuracy. PMID- 17353685 TI - Three and four-dimensional ultrasound in obstetrics and gynecology. AB - PURPOSE OF REVIEW: Developments in ultrasound in general, but even more so in three-dimensional ultrasound, parallel the growth in computing power and speed of computer technology. It is not surprising, therefore, that three-dimensional ultrasound technology is constantly evolving at a fast pace. The purpose of this article is to provide enhanced diagnostic capabilities for the obstetrical and gynecologic provider. RECENT FINDINGS: The most recent advances in three dimensional ultrasound have to do with two main features. First, an increasingly fast acquisition speed, enabling quick sequences of fast moving organs such as the heart to be captured. Second, the increasing number of different display modalities, making understanding and analysis of normal anatomy and pathology easier for clinicians. SUMMARY: This article highlights a selected number of clinical situations in which three-dimensional ultrasound meaningfully enhances the contribution of this fast evolving diagnostic imaging tool. PMID- 17353686 TI - Screening for aneuploidy in first and second trimesters: is there an optimal paradigm? AB - PURPOSE OF REVIEW: This review serves to explore the recent literature regarding aneuploidy screening in both first and second trimesters. We aim to construct a comparative analysis of a range of proposed strategies for screening for trisomy 21. RECENT FINDINGS: First trimester combined screening (sonographic nuchal translucency combined with serum markers pregnancy-associated plasma protein A and the free beta subunit of human chorionic gonadotrophin) has superseded second trimester serum screening (alpha-fetoprotein, total human chorionic gonadotrophin, unconjugated estriol with or without inhibin-A) as a screening paradigm for the detection of trisomy 21. This move is attributed to the recognition of superior detection rates, lower false-positive rates and earlier results associated with the former strategy. Septated cystic hygroma has been recognized as a distinct entity which confers a high risk of aneuploidy and structural malformations. Further advances in screening performance are achievable by combining the results of first and second-trimester screens in a sequential manner, with much interest generated by programs that only include second-trimester testing contingent upon first-trimester results. SUMMARY: Screening strategies for aneuploidy continue to evolve, with the most recent evidence favouring a contingent sequential approach. PMID- 17353687 TI - First and early second trimester fetal heart screening. AB - PURPOSE OF REVIEW: This review describes the recent advances in timing and effectiveness of first and early second trimester fetal echocardiography screening. RECENT FINDINGS: Fetal echocardiography can now be reliably performed from 11 weeks' gestation owing to improvements in ultrasound transducers and processors. Three-dimensional and four-dimensional ultrasound modalities in image acquisition and postprocessing analysis, including spatio-temporal image correlation, rendering three-dimensional power Doppler and high definition power flow Doppler, and B-flow have further improved our capabilities in this area. Fetal nuchal translucency measurement screening programs create a new population of at-risk pregnancies that will be referred for early fetal echocardiography. The majority of congenital heart defects, however, still occur in low-risk patients. Improved technology has lowered the gestational age at which fetal cardiac anatomy scanning can be reliably performed by properly trained and experienced examiners. SUMMARY: Early fetal echocardiography can be offered as a screening examination to at-risk and low-risk patients, with the proviso that it be repeated following screen-negative scans at mid-gestation to exclude later developing lesions. PMID- 17353688 TI - Cervical length and prediction of preterm delivery. AB - PURPOSE OF REVIEW: To present a summary of the literature and most recent advances in the clinical use of cervical length for the prediction of preterm birth. RECENT FINDINGS: Cervical length is predictive of preterm birth in all populations studied, including asymptomatic women with prior cone biopsy, mullerian anomalies, or multiple dilation and evacuations. While cervical length remains the most predictive measurement, funneling may add to its predictive value in certain populations. In terms of interventions aimed at preventing preterm birth once a short cervical length has been identified in asymptomatic women, recent data from a meta-analysis of all trials published so far point to the benefit of ultrasound-indicated cerclage in women with both a prior preterm birth and a cervical length less than 25 mm. Other interventions for a short cervical length such as progesterone and indomethacin are promising, but deserve further study before clinical recommendations can be made. In women with symptomatic preterm labor, a recent trial has shown that knowledge of cervical length (and fetal fibronectin) may be beneficial both in terms of time to triage and reduction of preterm birth. SUMMARY: Transvaginal ultrasound cervical length used as a screening tool for prediction and prevention of preterm birth can significantly improve the health outcomes of pregnant patients and their babies. PMID- 17353689 TI - Bibliography. Current world literature. Maternal-fetal medicine. PMID- 17353691 TI - High prevalence of elevated liver enzymes in blood donors: associations with male gender and central adiposity. AB - OBJECTIVE: Nonalcoholic fatty liver disease is an increasingly recognized condition, but its exact prevalence is unknown. In this prospective, multicenter study, we evaluated the prevalence of elevated alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl-transpeptidase levels as indirect markers of nonalcoholic fatty liver disease in volunteer blood donors as well as their associations with epidemiological and anthropometrical characteristics. METHODS: Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transpeptidase levels were determined in blood donors from four transfusion centers during the morning sessions of a 3-month period. Cases with positive hepatitis B surface antigen, anti-hepatitis C virus, anti-HIV or elevated liver enzymes and alcohol abuse were excluded. RESULTS: Abnormal liver enzymes were found in 17.6% of 3063 participants (alanine aminotransferase: 14.5%, aspartate aminotransferase: 4.6%, gamma-glutamyl-transpeptidase: 4.7%). Individuals with abnormal compared with those with normal liver enzymes or alanine aminotransferase values were more frequently men and had higher weight, body mass index, waist, hip and neck circumference (P<0.001 for all comparisons). The prevalence of abnormal liver enzymes was also associated with the transfusion center ranging between 8.8 and 22.1% (P<0.001) and alcohol consumption (P=0.001). In multivariate analysis, presence of elevated enzymes was independently associated with male sex, higher weight or body mass index, higher waist circumference and transfusion center. CONCLUSIONS: More than 15% of Greek blood donors exhibit elevated liver enzymes, most likely as a result of unrecognized nonalcoholic fatty liver disease. The prevalence of nonalcoholic fatty liver disease is mainly associated with male sex, obesity and waist circumference, but it may range significantly among different population groups. PMID- 17353692 TI - Bedside leucocyte esterase reagent strips with spectrophotometric analysis to rapidly exclude spontaneous bacterial peritonitis: a pilot study. AB - BACKGROUND: Spontaneous bacterial peritonitis, a potentially fatal complication of cirrhotic ascites, is diagnosed when the polymorphonuclear leucocyte count in the ascitic fluid is>250/mm. Manual laboratory counting of ascitic polymorphonuclear leucocytes is, however, labour-intensive, costly, results in diagnostic delay and it is not available in all hospitals as part of the 'out-of hours' service. Thus, a rapid diagnostic screening test for spontaneous bacterial peritonitis would be beneficial in this condition. An exciting new development in the diagnosis of spontaneous bacterial peritonitis is the use of bedside reagent strips; yet, concerns regarding the inherent subjectivity of result reading have prevented the widespread adoption of this technique in clinical practice. OBJECTIVE: To evaluate the combined use of a leucocyte esterase strip together with an objective portable spectrophotometric reading device in the diagnosis of spontaneous bacterial peritonitis when compared with standard manual laboratory polymorphonuclear leucocyte counting. METHODS: Nonselected cirrhotic patients undergoing diagnostic paracentesis had an ascitic sample sent for a conventional polymorphonuclear leucocyte count, Gram stain and culture. In addition, a sample was tested with a bedside Multistix 10SG reagent strip and the result was analysed by the Clinitek Status. The strip test was considered positive if it read anything other than negative (i.e. 'trace', '+1', '+2' or '+3'). RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the reagent strips to diagnose correctly spontaneous bacterial peritonitis when compared with the manual laboratory polymorphonuclear leucocyte count were 100, 91, 50, 100 and 92%, respectively. CONCLUSIONS: Bedside leucocyte esterase strips, spectrophotometrically read, can reliably exclude spontaneous bacterial peritonitis in patients with cirrhotic ascites. In our series, a negative strip result effectively ruled out this important condition, and suggests that the requirement for manual polymorphonuclear leucocyte counting in this setting could be removed. PMID- 17353693 TI - Prevalence of epigastric pain, heartburn and acid regurgitation in adolescents and their parents: evidence for intergenerational association. AB - BACKGROUND AND AIMS: Little is known of the epidemiology of upper gastrointestinal symptoms in adolescents. We examined the prevalence of, and the risk factors for, epigastric pain, heartburn and acid regurgitation in adolescents from Northern Ireland. PARTICIPANTS: A total of 1133 adolescents aged 12-18 years participated in this study. METHODS: Questionnaires were mailed to 2017 randomly selected individuals gathering information on symptoms of epigastric pain, heartburn and acid regurgitation. Prevalences of the symptoms in the individuals and their parents were calculated. Associations between potential risk factors such as age, sex, body mass index category, smoking and frequency of symptoms were examined for both adolescents and their parents. Logistic regression was used to examine the relationship between adolescent and parental symptoms. RESULTS: Symptoms of epigastric pain, heartburn and acid regurgitation were infrequent in adolescents, but were substantially more common in parents. Adolescents were more likely to experience these symptoms if either parent experienced them, the association being much stronger if both parents were symptomatic, for example, the odds ratio (95% confidence interval) for the individual having acid regurgitation if both parents had this symptom was 6.89 (1.32, 35.7). Symptoms were more likely in adolescents who smoked and whose parents smoked, who were from lower socioeconomic backgrounds, and who had higher body mass index. For parents, smoking was positively associated with all symptoms, whereas being overweight was related to frequency of heartburn and acid regurgitation. CONCLUSIONS: Strong relationships were seen between adolescent and parental reporting of dyspeptic symptoms. Although this could be due to intrafamilial clustering of environmental factors, the associations persisted after adjusting for these. Psychosocial factors or genetic predisposition may underlie the relationships. Further research is required to explore these relationships more fully. PMID- 17353694 TI - A surveillance programme for Barrett's oesophagus in a UK general hospital. AB - BACKGROUND: Surveillance programmes for oesophageal cancer in patients with Barrett's columnar-lined oesophagus have reported varying efficacies. AIM: To review the effectiveness of an endoscopic surveillance programme for patients with Barrett's oesophagus in a UK general hospital. METHODS: Patients with Barrett's oesophagus (> or =3 cm histologically proven columnar-lined oesophagus) were identified from endoscopic and histological records and outcomes recorded when surveillance was performed with 2-yearly endoscopies and quadrantic biopsies at 3 cm intervals. RESULTS: One hundred and twenty-one patients (24%) entered the surveillance programme (mean age 60.2 years, 69.5% men, mean length of Barrett's mucosa 7.5 cm) of 505 patients identified with Barrett's oesophagus. Two hundred and five endoscopies were performed over a mean follow-up of 3.5 years. Five cases of high-grade dysplasia and two cases of adenocarcinoma were detected during the surveillance. One patient with high-grade dysplasia refused surgery and died of oesophageal carcinoma. The other six patients underwent oesophagectomy and five of the six resected specimens showed early (Tis to T2, N0) adenocarcinoma. All six patients remained well and tumour free at 24 months. No interval oesophageal cancers occurred. CONCLUSION: This surveillance programme for classical Barrett's oesophagus was effective with six cancers being detected early and treated. The detection rate was 1/71 patient-years of surveillance. Endoscopic workload was not excessive and no interval cancers occurred. PMID- 17353695 TI - Multiband mucosectomy for endoscopic resection of Barrett's esophagus: feasibility study with matched historical controls. AB - BACKGROUND AND AIMS: Piece-meal endoscopic resection of early neoplastic lesions larger than 15-20 mm is a laborious procedure with the cap technique. Multiband mucosectomy is a new technique using a modified variceal band ligator. Submucosal lifting and prelooping of the snare in the cap is not necessary and multiple resections can be performed with a single snare. We prospectively evaluated the feasibility of multiband mucosectomy for widespread endoscopic resection in patients with a Barrett's esophagus with early neoplasia and compared results retrospectively with prospectively registered endoscopic cap resection procedures. RESULTS: Eighty multiband mucosectomy procedures were performed in 40 patients and 86 endoscopic cap resection procedures in 53 patients. Median duration of the multiband mucosectomy procedures was 37 vs. 50 min for endoscopic cap resection procedures (P=0.06); median duration per resection was 6 vs. 12 min, respectively (P<0.001). Mean diameter of the specimens was 17 vs. 21 mm (P<0.001). One perforation in the endoscopic cap resection group was successfully treated conservatively. Mild bleeding occurred in 6% of multiband mucosectomy and 20% of endoscopic cap resection procedures (P=0.012). Technical difficulties during multiband mucosectomy procedures included a decreased visibility owing to the black bands and the releasing wires. CONCLUSIONS: Multiband mucosectomy allows safe and easy widespread piece-meal resections in Barrett's esophagus. Time and costs appear to be saved compared with the cap technique, and multiband mucosectomy appears to cause less bleeding during the endoscopic resection procedure. Multiband mucosectomy, however, results in smaller specimens and is, therefore, most suited for en-bloc resection of lesions smaller than 10 mm or for widespread resection of flat mucosa. PMID- 17353696 TI - Rectal bleeding in children: endoscopic evaluation revisited. AB - OBJECTIVES: Rectal bleeding is an alarming event both for the child and parents. It is hypothesized that colonoscopy instead of sigmoidoscopy and adding esophago gastro-duodenoscopy in case of accompanying complaints, improves the diagnostic accuracy in children with prolonged rectal bleeding. STUDY DESIGN: All pediatric patients undergoing colonoscopy because of prolonged rectal bleeding over an 8 year period at the Emma Children's Hospital/Academic Medical Centre were reviewed. Patient demographics, clinical features, number and extent of endoscopic examinations and the endoscopic and histopathological findings were assessed. RESULTS: A total of 147 colonoscopies were performed in 137 pediatric patients (63 boys) because of prolonged rectal bleeding. Inflammatory bowel disease and polyp(s) were the most prevalent diagnoses. In 72% of patients diagnosed as Crohn's disease, focal, chronically active gastritis was seen on histology, giving support to the diagnosis Crohn's disease. In 22% of the cases polyps would have been missed in the case where only sigmoidoscopy was performed. No complications after endoscopic intervention were seen. CONCLUSIONS: Colonoscopy is the investigation of choice in children with prolonged rectal bleeding. In patients presenting with accompanying complaints such as abdominal pain or diarrhea, it is advisable to perform ileocolonoscopy combined with esophago-gastro-duodenoscopy. This combines a high diagnostic yield with a safe procedure. PMID- 17353697 TI - Attitudes toward genetic testing in patients with inflammatory bowel disease. AB - OBJECTIVES: Significant progress has been observed in our understanding of the role of genetics in inflammatory bowel disease susceptibility and phenotype. The clinical role of genetic testing for inflammatory bowel disease is not well developed, but may become important as more susceptibility genes are found. The aim of this study was to evaluate the attitudes of patients with inflammatory bowel disease toward genetic testing. METHODS: Two hundred and fifty patients (108 ulcerative colitis, 142 Crohn's disease) attending the outpatient clinic completed a questionnaire regarding clinical and family history data, as well as their attitudes toward genetic testing for inflammatory bowel disease. RESULTS: Ninety percent (225/250) of all patients expressed an interest in undergoing genetic testing themselves, with 87.6% (219/250) also expressing a desire for their children to be tested. Although the proportion of ulcerative colitis and Crohn's disease patients interested in testing was similar, levels of interest decreased as the predictive value of a putative genetic test decreased. A comparable proportion of those with [80/86 (93.0%)] and those without [145/164 (88.4%)] a family history of inflammatory bowel disease expressed an interest in genetic testing. More patients who had received immunomodulating or biologic therapies [123/128 (96.1%)], however, wished to undergo testing than those who had not received these medications [78/93 (83.9%; P<0.01)]. CONCLUSION: Patients with inflammatory bowel disease have a high level of interest in genetic testing, both for themselves and for their children, and this will have an impact upon the provision of genetic services as progress is made toward defining a clinical role for inflammatory bowel disease susceptibility genes. PMID- 17353698 TI - Repeated courses of transarterial embolization with polyvinyl alcohol particles: 'long life elixir' in a cirrhotic patient with unresectable hepatocellular carcinoma. AB - Chemoembolization improves survival in selected cirrhotic patients with hepatocellular carcinoma, but prolonged survival is unusual. In this study, a 70 year-old cirrhotic patient, who had a histologically proven hepatocellular carcinoma of 5 cm diameter, embolization with polyvinyl alcohol particles alone, without chemotherapeutic agent, has resulted in continued survival, of 5 years to date, with virtual elimination of residual hypervascularity following 10 sessions of embolization, and with continued patency of the injected branch of the hepatic artery. Provided liver function is maintained, embolization alone appears a feasible long term and effective therapy for unresectable hepatocellular carcinoma. PMID- 17353699 TI - Inflammatory pseudotumour of the liver: the residuum of a biliary cystadenoma? AB - Inflammatory pseudotumour is a rare form of a liver mass. We report the case of a 28-year-old man presenting with obstructive jaundice, in whom an inflammatory pseudotumour arose with the resolution of a mucus secreting cystic liver lesion. The initial features suggested an intrahepatic cystadenoma or cystadenocarcinoma, which on its involution left a solid mass. Histopathology showed an inflammatory pseudotumour with no evidence of malignancy. A similar case has been reported recently, with the development of an inflammatory pseudotumour following collapse of a liver cyst seen on imaging. These two cases may shed some light on the origins of these rare liver lesions. PMID- 17353700 TI - Dual polymorphisms in UDP-glucuronosyltransferases 1A1 and 1A6: a novel mechanism for hyperserotoninaemia in Gilbert's syndrome mimicking carcinoid syndrome? AB - Gilbert's syndrome is a common inherited disorder, in which genetic defects in uridine diphosphate-glucuronosyltransferase 1A1 lead to deficient glucuronidation of bilirubin and hence hyperbilirubinaemia. Although usually considered asymptomatic, Gilbert's syndrome can be associated with gastrointestinal and psychiatric symptoms unexplained by the metabolic defect. Genetic polymorphism of a closely related enzyme, uridine diphosphate-glucuronosyltransferase 1A6, results in altered metabolism and elimination of serotonin. On the basis of a case of hyperserotoninaemia in the absence of a detectable carcinoid tumour in a patient with Gilbert's syndrome, who presented with a history of night sweats, flushing, abdominal discomfort and intermittent diarrhoea, we propose that in a subgroup of Gilbert's syndrome patients, homozygocity for dual uridine diphosphate-glucuronosyltransferase 1A1 and uridine diphosphate glucuronosyltransferase 1A6 polymorphisms may lead to combined hyperbilirubinaemia and hyperserotoninaemia. The latter may account for symptoms experienced by patients with Gilbert's syndrome hitherto considered unrelated to, or unexplainable by, the known defect in bilirubin metabolism. PMID- 17353702 TI - Intestinal tuberculosis mimicking Crohn's disease: lessons relearned in a new era. AB - Over 400 000 cases of tuberculosis existed in Europe in 2002, 1% of which were intestinal tuberculosis. With population migrations on the increase, physicians may have to face an increase in intestinal tuberculosis. One of the attributes of intestinal tuberculosis is its ability to present in nonspecific ways and to mimic other disorders, in particular inflammatory bowel disease. We present a case series of intestinal tuberculosis presenting as inflammatory bowel disease and referred for management to a specialized clinic in inflammatory bowel disease, followed by a discussion of the difficulties encountered with this condition. We highlight the consequences that misdiagnosis can have, in an era where population demographics are changing in Europe and where immunomodulators and biological agents have the potential to do more harm than good. PMID- 17353701 TI - Deleterious effect of nitric oxide inhibition in chronic hepatopulmonary syndrome. AB - On the basis of limited experimental and clinical studies, increased activity of the vasodilatory nitric oxide-cyclic guanosine monophosphate pathway is considered to play a key role in the pathogenesis of hepatopulmonary syndrome. We report a 46-year-old woman with Child-Pugh class C cirrhosis and progressive dyspnoea for 12 months. Investigations revealed elevated circulating concentrations of nitric oxide metabolites and exhaled nitric oxide levels, an hyperdynamic circulation with low systemic vascular resistance and mean arterial pressure, a large right to left intrapulmonary shunt fraction on radiolabelled macroaggregated albumin perfusion scanning, positive contrast-enhanced echocardiography, reduced diffusion capacity of carbon monoxide, hypoxaemia and orthodeoxyia, all in keeping with severe hepatopulmonary syndrome. Sequential inhibition of the nitric oxide-cyclic guanosine monophosphate pathway using curcumin (diferuloylmethane), terlipressin and methylene blue was associated with substantial improvements in vascular tone and the hyperdynamic circulation. No improvement, however, in the intrapulmonary shunt was demonstrated. Both hypoxaemia and orthodeoxia were substantially, reproducibly and reversibly worsened with all three treatments. Our findings argue against the contention that intrapulmonary shunting and impairment in arterial oxygenation in hepatopulmonary syndrome are necessarily the consequence of on-going, nitric oxide-cyclic guanosine monophosphate-mediated vasodilatation, at least in the chronic stage, and, given the possibility of substantial worsening of pulmonary oxygen exchange, suggest that inhibition of the nitric oxide-cyclic guanosine monophosphate pathway should be avoided in this setting. PMID- 17353703 TI - Improving patient safety. PMID- 17353704 TI - Food and Drug Administration: 100 years of protection. PMID- 17353705 TI - Medication errors and the home care patient. AB - Medication errors specific to home care include taking the wrong dose or quantity of medications, omitting medications, or taking an unauthorized drug. This article includes information regarding types of errors, contributing factors, and potential solutions to the identified problems. PMID- 17353707 TI - Home care physical therapy for the cancer patient. PMID- 17353708 TI - Certification in tobacco treatment: why should home care nurses bother? PMID- 17353709 TI - Putting the pieces together: private-duty home healthcare and geriatric care management: one home health agency's model. AB - This article examines how one home health agency successfully launched a geriatric care management program. The methods of market assessment, the necessary staff to implement the program, and an overview of geriatric care management in general are presented together with an actual case study. PMID- 17353710 TI - A comprehensive fall prevention program for assessment, interventions, and referral. AB - Christiana Care Visiting Nurse Association (VNA) developed a fall risk assessment using information obtained from the Outcomes and Assessment Information Set (OASIS) assessment. The fall risk assessment tool has been tested using a retrospective record review. A risk-specific intervention guide and postfall algorithm also are parts of the Fall Prevention Program. The Fall Prevention Program has improved patient safety and reduced emergent care related to injury from a fall. PMID- 17353712 TI - A description of adverse events in home healthcare. AB - Patient safety has taken on increasing importance in the American healthcare system, yet there is little information on patient safety in home healthcare. The current study aimed to describe the most frequent adverse events defined by the Centers for Medicare & Medicaid Services among the national population of patients receiving home healthcare in 2003, and to compare characteristics between patients who experience adverse events and those who do not. The findings show that 13% of all home healthcare patients had an adverse event, with 80% experiencing only 1 adverse event. More than three fourths of the adverse events were associated with discharge to the community and required continued assistance. Patients who experienced adverse events were older, had more depressive symptoms and behavioral problems, and were more functionally impaired. Women had a slightly lower relative risk of an adverse event (.98), whereas patients of minority ethnicity had a slightly higher relative risk (1.06). These findings suggest that home healthcare agencies may need to spend more time on discharge planning after home healthcare and work with existing community providers. The findings also raise questions regarding the appropriateness of these adverse events and whether there are additional adverse events that warrant monitoring and follow-up evaluation. PMID- 17353711 TI - Managing the care of patients discharged from home health: a quiet threat to patient safety? AB - Threats to patient safety can originate from the overuse or underuse of care, in addition to provider-initiated errors. The past decade has seen a dramatic decrease in the duration and volume of home health services provided per patient by Medicare-certified home health agencies (HHAs). Research findings have been mixed with respect to the impact of home health utilization on patient safety and outcomes. This study aimed to explore a related yet fundamental question: How confident are home health nurses that their patients can manage their care when discharged from home health services? PMID- 17353713 TI - Home healthcare nurse recruitment and retention: tips for retaining nurses: one state's experience. AB - During March 2006, a series of statewide conferences was held to discuss home care outcomes, with a special emphasis on strategies for retaining home care nurses. Administrators and owners of home care agencies in one state with high staff retention and a low rate of turnover participated in four panel discussions to share best practices. The discussions were sponsored by TMF Health Quality Institute, the Quality Improvement Organization (QIO). In addition to practitioner panels, a review of the home care research literature on recruitment and retention was presented. This article is derived from the combined evidence shared during those meetings. The three most common strategies for retaining nursing staff were the use of case management or primary nursing, management participation in direct patient care, and open lines of communication. PMID- 17353714 TI - Caring for culturally diverse patients: one agency's journey toward cultural competence. AB - Across the United States, spanning urban, suburban, and rural areas, racial and ethnic minority populations are growing faster than White English-speaking populations. Increasingly, healthcare professionals are providing care to patients from diverse cultures with traditions and beliefs that may be unfamiliar and with health practices that may conflict with western medicine. How can home care and hospice professionals navigate this new terrain and communicate effectively across cultural boundaries? One agency's journey toward cultural competency may provide a road map for others. PMID- 17353716 TI - Legislative and regulatory considerations for home health nurses. AB - "Government's influence on professional practice, quality healthcare, and agency administration increases with each passing year. Federal, state, and local laws and regulations impact the day-to-day operations...." Therefore, it is important for professional nurses to understand both legislative and regulatory processes, identify resources, and take action when necessary (, p. 675). PMID- 17353717 TI - Promoting safety and security at home. PMID- 17353718 TI - Unacceptable risks: VNAs work to prevent falls. PMID- 17353719 TI - Specific human leukocyte antigen alleles associated with HIV-1 infection in an Indian population. PMID- 17353720 TI - Selective drug taking during combination antiretroviral therapy. PMID- 17353721 TI - Response to "CD4 cell count natural history and informative censoring in sub Saharan Africa". PMID- 17353724 TI - Pain, disability, and symptoms among siblings of children with functional abdominal pain. AB - OBJECTIVE: To examine reports of pain, disability, and somatic and psychological symptoms among siblings of children with functional abdominal pain (FAP) and siblings of "healthy" comparison children. METHODS: This survey study explored two groups of participants (FAP and healthy) consisting of (1) children with FAP and their siblings and parents and (2) healthy comparison children and their siblings, and parents. Participants included 13 FAP families and 10 healthy comparison families. Siblings and children were between 8 and 14 years of age. Measures included the Behavioral Assessment System for Children, Abdominal Pain Index, Children's Somatization Inventory, Functional Disability Inventory, and Family Inventory of Life Events. Cross-sectional data were analyzed using correlations and analysis of variance techniques. RESULTS: Siblings of children with FAP reported significantly greater mean levels of emotional/ behavioral symptoms than siblings of healthy comparison children. No significant between group differences were identified in FAP and healthy comparison parents' reports of siblings' pain or emotional/behavioral symptoms. There were significantly more persons with pain problems living in the homes of FAP families. Among FAP families, a greater number of parent-reported family stressful life events was significantly associated with sibling functional disability and somatic symptoms. CONCLUSION: This investigation suggests that siblings of children with FAP experience more emotional/behavioral symptoms than peers and that their symptoms are not readily identified by parents. These findings highlight the importance of considering the psychological functioning of "unaffected" siblings and family stressors when children present with recurrent pain complaints. PMID- 17353725 TI - Caregiver-reported health outcomes of preschool children born at 28 to 32 weeks' gestation. AB - OBJECTIVE: We conducted a population-based survey of caregivers of all preschoolers at 42 months of age who had been admitted at birth in 1996-1997 to a tertiary neonatal intensive care unit in British Columbia (BC), Canada. METHODS: In this paper, we examine health status (measured by Health Status Classification System [HSCS-PS]), health-related quality of life (HRQL) (measured by Infant and Toddler Quality of Life Questionnaire), and behavioral outcomes (measured by Child Behavior Checklist) of the preschoolers in the sample who were born at 28 32 weeks gestational age (GA) in comparison to those born at <28 weeks GA. In addition, we compare these outcomes to health status, HRQL, and behavioral outcomes of a cohort of healthy full-term infants identified from the primary care practices at two of the hospital sites in BC in 1996-1997. RESULTS: From the total identified sample of 555 children, the survey was completed for 50 children born at <28 weeks GA, 201 children born at 28-32 weeks GA, and 393 healthy full term subjects. The developmental outcomes of the preschoolers born at 28-32 weeks GA was very similar to those born at <28 weeks GA. We also found increased parental report of problems related to health status and HRQL among the 28-32 weeks GA group. When compared with the term cohort, the 28-32 weeks GA group had poorer outcomes in all HRQL domains. CONCLUSION: This study discusses the importance of continued neurodevelopmental follow-up care of infants born at 28 32 weeks GA in addition to those infants born <28 weeks GA. PMID- 17353727 TI - Mental health problems in children and caregivers in the emergency department setting. AB - INTRODUCTION: Although mental health problems are increasing in the primary care sector, the prevalence of mental health problems in families presenting for nonpsychiatric complaints in the emergency department (ED) setting is generally unknown. As such, we set out to assess the frequency of mental health concerns and associated risk factors in children presenting for care in a pediatric ED. METHODS: A total of 411 mother-child dyads were randomly selected during a 2-year period from the less acute area of a large pediatric ED. Mothers were interviewed for child mental health concerns using structured diagnostic instruments. Mothers were also interviewed for their own mental health symptoms. Risk factor analysis for the outcome of a pediatric mental health concern was performed using bivariate and multivariate techniques. RESULTS: Of all children, 45% met criteria for a mental health concern, with 23% of all children meeting criteria for two or more mental health concerns; 21% of mothers screened positive for a mental health problem themselves. Once adjusted, children whose mothers' screened positive for a mental illness were more likely to have a mental health concern themselves. CONCLUSION: There is a large burden of mental health concerns in children and their mothers presenting to the ED for medical care. Efficiently and accurately identifying mental illness in children presenting to a pediatric ED is the first step in the intervention process for a population that might otherwise slip through the system. PMID- 17353728 TI - Barth syndrome is associated with a cognitive phenotype. AB - OBJECTIVE: Barth syndrome is a rare, X-linked recessive disorder that affects only boys. The cardinal characteristics include growth retardation, cardioskeletal myopathy, chronic or cyclic neutropenia, and 3-methylglutaconic aciduria. A preliminary study of five young boys with Barth syndrome suggested a distinct cognitive phenotype. METHODS: The present study was designed to explore whether additional evidence for a cognitive phenotype emerged from a larger sample. A psychoeducational assessment battery was administered to 15 boys with Barth syndrome. Data from these boys were compared to data from 15 typically developing boys individually matched on age and grade in school to each of the 15 boys with Barth syndrome. RESULTS: Although boys with Barth syndrome had age appropriate performance on all measures of reading-related skills, their performance on mathematics and visual spatial tasks was significantly lower than that of boys in the comparison group. Moreover, specific aspects of visual short term memory also differed from available norms. CONCLUSION: Our findings support the validity of the preliminary findings and reflect a higher incidence of cognitive difficulties in boys with Barth syndrome relative to boys in the comparison group. Coupled with the fatigue regularly experienced by boys with Barth syndrome, our findings indicate that educational support should be implemented during the early school-age years for children with Barth syndrome. PMID- 17353729 TI - Early acceleration of head circumference in children with fragile x syndrome and autism. AB - OBJECTIVE: Head circumference (HC) growth has been shown in several studies to be accelerated early in life in both fragile X syndrome (FXS) and autism spectrum disorders (ASDs), but the rates of growth have not been compared between those with only FXS and those with FXS and ASD (FXS + ASD). METHODS: We hypothesized that individuals with FXS + ASD would have significantly larger HCs from individuals with only FXS and that there would be an early acceleration of HC in both the FXS-only and FXS + ASD groups. HC measurements were available retrospectively for 44 males, five and younger, with FXS, of whom 22 also had ASD. Measurements over time were available for 24 of the 44 children. HC percentiles were compared between the groups in two ways: by focusing on cross sectional subsamples and by fitting hierarchical linear models to the full sample. RESULTS: Neither group differed significantly from the norm in the first year of life (p > 0.2). At 30 months, the FXS + ASD group was 27 percentile points above the norm (p = .0125), whereas the FXS-only group did not differ from the norm. At 60 months, the FXS-only group was 21 percentile points above the norm (p = .029), whereas the FXS + ASD group did not differ from the norm. CONCLUSION: The group difference in HC growth rate may differentiate brain development in individuals with FXS-only versus those with FXS + ASD. PMID- 17353730 TI - Depressive symptoms in mothers of prematurely born infants. AB - OBJECTIVE: This longitudinal, descriptive study described the level of depressive symptoms in mothers of preterm infants from birth through 27 months corrected age and examined factors associated with depressive symptoms. The framework for the study was guided by an ecological developmental systems perspective and an adaptation of the Preterm Parental Distress Model. METHODS: In this model, we hypothesize that a mother's emotional distress to the birth and parenting of a prematurely born child is influenced by personal and family factors, severity of the infant's health status, and illness-related stress and worry. Participants were 102 mothers of preterm infants who were off the ventilator and not otherwise dependent on major technology at enrollment. RESULTS: Mean depressive symptoms scores on the Center for Epidemiologic Studies Depression Scale (CES-D) during hospitalization were high and more than half the mothers (63%) had scores of > or =16 indicating risk of depression. Depressive scores declined over time until 6 months and then were fairly stable. Unmarried mothers, mothers of infants who were rehospitalized, and mothers who reported more maternal role alteration stress during hospitalization and worry about the child's health had more depressive symptoms through the first year. Mothers who reported more parental role alteration stress during hospitalization (odds ratio [OR] = 1.570, 95% confidence interval [CI]: 1.171-2.104) and more worry about the child's health (OR = 2.350, 95% CI: 1.842-2.998) were more likely to experience elevated CES-D scores that put them at risk of depression. Also, mothers of rehospitalized infants had decreasing odds of elevated CES-D scores over time (OR = 0.982 per week, 95% CI: 0.968-0.996). CONCLUSIONS: Findings have implications for the support of mothers during hospitalization and in the early years of parenting a preterm infant. PMID- 17353731 TI - Pain, disability, and symptoms among siblings of children with functional abdominal pain. PMID- 17353732 TI - Use of developmental milestones in pediatric residency training and practice: time to rethink the meaning of the mean. AB - OBJECTIVE: Pediatricians frequently report the use of developmental milestones in monitoring young children's development, despite evidence that use of screening tools improves detection of developmental delays. METHODS: Core texts in the field of pediatrics and developmental-behavioral pediatrics were reviewed for content and presentation on child development. Most texts included and many focused on developmental milestones, many with an emphasis on 50th percentile milestone data. Problems and limitations in the use of 50th percentile milestones to monitor young children's development and to identify children whose development is suspicious for delay, include questionable utility in clinical decision making and the potential to increase parental anxiety. RESULTS: The recommendation is made to reconsider a focus on 50th percentile milestone data in pediatric training and practice, in favor of measures that have better clinical utility and are more psychometrically sound. CONCLUSION: A conceptual approach to the presentation of developmental milestones differentiates the use of the 10th, 50th, and 90th percentiles of age of achievement of skills, based on the clinical purpose of surveillance. PMID- 17353734 TI - Juan: a 9-year-old Latino boy with ADHD. PMID- 17353739 TI - Psychosocial functioning of children with AIDS and HIV infection: review of the literature from a socioecological framework. AB - Despite the development of highly effective treatments for the disease, pediatric human immunodeficiency virus (HIV) infection continues to affect a substantial number of families both in the United States and worldwide. This article reviews the psychosocial functioning of children with HIV, taking a socioecological perspective to organize the literature. When compared to children from similar socioeconomic situations, children with HIV demonstrate a range of possible outcomes. However, beyond the direct effects on children's neurocognitive and psychological functioning, HIV infection may disrupt many of the social support systems that children depend on for optimal development. Further, unlike many other illnesses, children with HIV infection are more likely to experience parental illness and possible death, social stigmatization, and the prospect of lifelong adherence to complicated medical regimens. Families face difficult decisions regarding disclosure of the illness both to the child and to others within and outside of the family. Children who are disclosed to about their illness generally evidence better adjustment. Similarly, appropriate disclosure outside of the immediate family may confer some benefits to the child in terms of psychological and physical health. However, research into the larger social ecologies of youth with HIV remains lacking, limiting the conclusions that can be drawn regarding longer term outcomes. PMID- 17353742 TI - Improving the quality of nursing care using the medical expenditure panel survey data. PMID- 17353743 TI - Hastings Center special report: the ethics of using QI methods to improve health care quality and safety. PMID- 17353744 TI - Strategies to increase reporting of near misses and adverse events. PMID- 17353745 TI - Development of an evidence-based pediatric fall prevention program. PMID- 17353746 TI - Magnet status: a journey, not a destination. PMID- 17353747 TI - State nursing shortages and patient satisfaction: more RNs--better patient experiences. AB - This study of 827,430 patients, 733 hospitals, and 25 states compares state performance in patient satisfaction with the supply of registered nurses. A significant, positive relationship exists between a state's supply of registered nurses and patients' evaluations of their care experiences. Hospitals in states with nursing shortages may be challenged by national comparisons of patient satisfaction and should take these results into account when devising their quality improvement strategy. PMID- 17353750 TI - Falls prevention at Mayo Clinic Rochester: a path to quality care. AB - Falls prevention is a complex problem. Following in the footsteps of an earlier fall prevention team, the Safe Landings Fall Prevention Team used many strategies for implementing a fall prevention/reduction program. The tactics we used to prevent falls combined with the adoption of a fall assessment risk model are shared. PMID- 17353749 TI - Risk items associated with patient falls in oncology and medical settings. AB - The aim of this study was to determine whether items on a falls risk-assessment tool, made up of brief cognitive and physical measures that nurses use in practice, differentiated fallers and nonfallers in oncology and medical settings. A measure of leg muscle strength clearly distinguished between fallers and nonfallers, with the latter having stronger leg muscles. For nursing practice, the assessment of patients' muscle strength seems to be the most useful scale for identifying potential fallers. PMID- 17353751 TI - Patient falls and open visiting hours: a case study in a Taiwanese medical center. AB - This study investigated the linkages between patient falls and open visiting hours in an acute care setting in Taiwan. The activities of the accompanying family members/aides when patients fell were analyzed. More than 35% of the family members/aides who were watching patients were ineffective in preventing the falls. PMID- 17353752 TI - Families speak about inpatient end-of-life care. AB - Death is an emotional event that leaves lasting memories for the bereaved. This article describes the qualitative analysis of a mailed family survey addressing experiences with community hospital inpatient end-of-life care. Family members identified and appreciated symptom management and caring behaviors such as compassion and communication; they also noted the absence of these caring behaviors. Effective application of these behaviors to the dying experience should improve family satisfaction with end-of-life care. PMID- 17353753 TI - Improving patient safety and communication through care rounds in a pediatric oncology outpatient clinic. AB - The last 25 years have brought major changes to our Outpatient Pediatric Oncology Clinic: a 400% increase in patient volume, a 7-fold increase in chemotherapy infusions, and a major shift in the care delivery system. These changes and a recent sentinel event provided the impetus to improve communication by instituting daily care rounds with an interdisciplinary team. Care rounds have become the standard of practice in this clinic and are perceived to have improved communication and patient safety. PMID- 17353754 TI - A plan for achieving significant improvement in patient safety. AB - Improvement in systems that ensure safety in the provision of care is a high priority to hospital administrators, clinicians, and patients. Research to determine the approaches and methods that will result in the most significant patient safety improvements is underway but more is needed. This article describes the process for improving patient safety adopted at one hospital. Results of these efforts demonstrate significant improvement in staff understanding of patient safety measures. Staff survey results are supported by improvement in clinical indicators. Recommendations for future action and implications for other hospitals are discussed. PMID- 17353755 TI - Expert standards in nursing as an instrument for evidence-based nursing practice. AB - This article describes the model of the German Network for Quality Development for developing, consenting, and implementing evidence-based national nursing standards. The advantages and challenges of implementing these expert standards are discussed. Finally, the influence of the national standards on the profession and quality policy is outlined. PMID- 17353756 TI - Using electronic wristbands and a triage protocol to protect mental health patients in the emergency department. AB - In the emergency department of Mercy Hospital, concerns about possible elopement of mental health patients led to the use of the services of security officers, who were called for an average of 40 patient watches per week. Modified electronic wristbands, paired with a triage protocol, have significantly decreased the need for patient watches and decreased security costs. PMID- 17353757 TI - Quality of pediatric nursing care in Finland: children's perspective. AB - This study assessed the quality of pediatric nursing care as perceived by children (N = 388) aged 7 to 11 in Finland. The children rated as excellent the nursing environment, the nurses' humanity and trustworthiness, and caring and communication. They were most critical about the nurses' entertainment activities such as playing with them. Children's age and type of admission were both related to the amount of information they received. The instrument used in the study needs to be developed and tested further. PMID- 17353759 TI - Variation in the use of mechanical ventilation for asthma: how big a gap? PMID- 17353760 TI - Understanding the role of von Willebrand factor and its cleaving protease ADAM TS13 in the pathophysiology of critical illness. PMID- 17353761 TI - Pain assessment should not have to be painful. PMID- 17353762 TI - Detecting medication errors: a job for Six Sigma. PMID- 17353763 TI - Cerebral oximetry: patience is a virtue but not a virtue for the patient, yet? PMID- 17353764 TI - Errors in placement of enteral tubes in critically ill children: are we foolproof yet? PMID- 17353765 TI - Predicting failed extubation in critically ill children. PMID- 17353767 TI - Montelukast in chronic graft-versus-host disease: a breath of fresh air? PMID- 17353768 TI - Measuring renal function in solid organ transplant recipients. PMID- 17353769 TI - In vivo and in vitro effect of sirolimus on insulin secretion. AB - BACKGROUND: The effects of sirolimus on insulin secretion are still debated. Our aim was to investigate the effects of sirolimus, both (1) in vivo in healthy minipigs; and (2) in vitro on human islets. METHODS: (1) Ten minipigs were evaluated during three successive stages: (a) basal; (b) at the end of a 4-week period of treatment with sirolimus; and (c) after a 4-week period of wash-out. We evaluated insulin secretion with the acute insulin response (AIR), and glucose tolerance with the glucose disposal rate (GDR). (2) Insulin content, stimulation index, adenosine triphosphate (ATP), and apoptosis were measured in human islets treated in vitro with sirolimus at therapeutic and supratherapeutic concentrations. RESULTS: (1) Basal and stimulated insulin levels and GDR increased during sirolimus administration and returned to baseline after a wash out period; (2) regardless of culture duration, sirolimus dose-dependently decreased apoptosis and increased insulin content. Stimulation indexes and ATP were also significantly enhanced but only at therapeutic concentrations. CONCLUSIONS: This study suggests that sirolimus, at plasma-drug concentrations usually targeted in clinical practice, (1) increases basal and stimulated insulin levels in vivo and insulin content in vitro regardless of culture duration; (2) is able to reduce apoptosis. These findings may partly underlie the improved results of islet transplantation. PMID- 17353770 TI - Cardiac transplantation using extended-donor criteria organs for systemic amyloidosis complicated by heart failure. AB - BACKGROUND: Systemic amyloidosis complicated by heart failure is associated with high cardiovascular morbidity and mortality. Heart transplantation for patients with systemic amyloidosis is controversial due to recurrence of disease in the transplanted organ or progression of disease in other organs. METHODS: All patients with systemic amyloidosis and heart failure referred for heart transplant evaluation from 1997 to 2004 were included in this retrospective cohort analysis. An interdisciplinary protocol for cardiac transplantation using extended-donor criteria organs, followed in 6 months by either high-dose chemotherapy and stem cell transplantation for patients with primary (AL) or by orthotopic liver transplantation for familial (ATTR) amyloidosis, was developed. Survival of the transplanted amyloid cohort was compared to survival of those amyloid patients not transplanted and to patients transplanted for other indications. RESULTS: A total of 25 patients with systemic amyloidosis and heart failure were included in the study; 12 patients received heart transplants. Amyloid heart transplant recipients were more likely female (58% vs. 8%, P=0.02) and had lower serum creatinine (1.3+/-0.5 vs. 2.0+/-0.7 mg/dL, P=0.01) than nontransplanted amyloid patients. Survival at 1-year after heart transplant evaluation was higher among transplanted patients (75% vs. 23%) compared to patients not transplanted (P=0.001). Short-term survival posttransplant did not differ between transplanted amyloid patients and contemporaneous standard and extended-donor criteria heart transplant patients (P=0.65). CONCLUSIONS: Cardiac transplantation for amyloid patients with extended-donor criteria organs followed by either stem cell or liver transplantation is associated with improved survival compared to patients not transplanted. Short- to intermediate-term survival is similar to patients receiving heart transplantation for other indications. This clinical management strategy provides cardiac amyloid patients a novel therapeutic option. PMID- 17353771 TI - Preliminary experience with cinacalcet use in persistent secondary hyperparathyroidism after kidney transplantation. AB - BACKGROUND: There is limited experience with the use of cinacalcet in the treatment of persistent secondary hyperparathyroidism after kidney transplantation. METHODS: We retrospectively analyzed our experience in 18 renal allograft recipients who initiated cinacalcet therapy from 1 month to 23 years (median 3 years) posttransplantation and were maintained on the drug for 6 months. The daily dose was titrated from 30 mg up to a maximum of 180 mg to achieve a reduction in serum intact parathyroid hormone (PTH) levels. RESULTS: Sustainable, significant decreases in mean calcium and alkaline phosphatase were noted at 1 month and intact PTH by 3 months, with 50% of patients achieving at least a 30% drop in PTH levels at 6 months. Serum phosphorous increased at 6 months, whereas urine N-telopeptides decreased. There were no significant changes in serum osteocalcin, albumin, and hemoglobin levels. We did not observe a tachyphylaxis phenomenon. Two patients reported occasional nausea, but did not require medication discontinuation. Estimated glomerular filtration rate did decrease progressively over the 6-month period. CONCLUSION: Cinacalcet appears to be an effective drug for the treatment of posttransplant hypercalcemia due to persistent secondary hyperparathyroidism. Further studies with more patients and longer follow-up will be needed to better elucidate the efficacy/safety profile for this agent, particularly with regard to long-term bone histology and renal outcomes. PMID- 17353772 TI - Does renal function deteriorate more rapidly in diabetic cardiac transplant recipients? AB - BACKGROUND: Selection criteria for cardiac transplant candidates with diabetes mellitus (DM) have been liberalized resulting in increased numbers of diabetic patients receiving organs. Calcineurin inhibition results in nephrotoxicity. Whether this nephrotoxicity is accelerated in diabetic heart transplant recipients is unknown. METHODS: To investigate this question, we derived the glomerular filtration rate (GFR) at transplant and at multiple time intervals thereafter for adult heart transplants performed from January 1, 2000 to January 1, 2005. GFR was estimated using the Modification of Diet in Renal Disease Study equation (GFRMDRD) and the Cockcroft-Gault (GFRCG) formula. RESULTS: In all, 257 patients were nondiabetic and 102 patients were diabetic before and after transplant. The diabetic patients were older (57+/-8 vs. 53+/-13 years; P<0.01) and had greater body mass index (27.5+/-5.1 vs. 25.5+/-4.4 kg/m; P<0.01) than nondiabetic patients. Baseline renal function was significantly reduced in diabetic patients with higher serum creatinine (1.6+/-0.5 vs. 1.4+/-0.5 mg/dL), lower GFRCG (65+/-27 vs. 73+/-35 mL/min), and lower GFRMDRD (54+/-23 vs. 65+/-32 mL/min; all P<0.01) than nondiabetic patients. All patients were treated with cyclosporine or tacrolimus posttransplant. The change in the GFRMDRD in nondiabetic and diabetic patients was constant and comparable at 1, 2, and 3 years posttransplant. In normal subjects, GFRMDRD declined from baseline by 7+/ 26, 5+/-23, and 7+/-23 mL/min(2) and in the diabetic patients was 13+/-22, 9+/ 26, 10+/-22 ml/min(2) at 1, 2, and 3 years, respectively (P=NS). CONCLUSION: This data suggests that nephrotoxicity posttransplant is not accelerated in diabetic recipients. PMID- 17353773 TI - Telemetric monitoring of pulmonary function after allogeneic hematopoietic stem cell transplantation. AB - BACKGROUND: Late-onset noninfectious pulmonary complications (LONIPC) are both frequent and severe after allogeneic hematopoietic stem cell transplantation (HSCT). The high mortality rate (40-80%) may be related to delayed diagnosis. We assessed the use of telemetric home surveillance of pulmonary function for early diagnosis of LONIPC in transplant recipients. METHODS: This prospective study monitored pulmonary function in 37 allogeneic HSCT recipients. About 3 months after HSCT, they received a portable spirometer that measured forced vital capacity, forced expiratory volume per second, and midexpiratory flow 25-75 (MEF25-75). Data were transmitted twice weekly by telephone. Conventional plethysmography confirmed any significant deterioration (>20%). RESULTS: Thirteen episodes of spirometric deterioration were detected by telemetry in 11 patients during a median 17-month (4-41) follow-up period after transplantation. In these cases, examinations including spirometry, high-resolution thoracic computed tomography and bronchoalveolar lavage diagnosed LONIPC in eight episodes in seven patients (cumulative incidence 23.4%, SE 0.08, at month 24 after transplant): bronchiolitis obliterans (BO, n=3), interstitial pneumonia (IP, n=4), or both BO and IP (n=1). Five episodes improved and three were stabilized with increased immunosuppressive therapy. At the last follow-up, of the seven patients with LONIPC, one successfully stopped immunosuppressive therapy, two were receiving low-dose mycophenolate mofetil, and four were receiving low-dose corticosteroid therapy. There were no cases of respiratory failure and no patient died from LONIPC. CONCLUSION: Telemetric home monitoring of pulmonary function is a useful procedure for early diagnosis of LONIPC before clinical pulmonary symptoms and may improve outcome after allogeneic HSCT. PMID- 17353774 TI - Cold ischemia time in renal transplantation is reduced by a timesheet in a French transplant center. AB - BACKGROUND: Cold ischemia time (CIT) is associated with delayed graft function (DGF) and transplant outcome. Several strategies to reduce CIT have been proposed. We retrospectively analyzed the effect of using a timesheet on CIT in our center. METHODS: In the last 2 years, we have introduced a timesheet to study the course of organ procurement and transplantation during CIT. Results of our 2 year program (121 transplantations) were compared to those in the preceding 2 years (151 transplantations). The timing of each intervention and the influence of national sharing policy and priority recipients were recorded. RESULTS: CIT decreased significantly from 21.45 to 13.27 hours (P<0.0001) and the DGF rate from 34.7 to 20.7% (P=0.011). Usually, human leukocyte antigen typing was done before kidney removal and the recipient was evaluated in the evening or at night for a transplant procedure starting in the morning. Only 1 of 121 transplantations started during the night. The availability of an operating room was the limiting factor. Sharing organs for national priority with a crossmatch having been performed increased CIT twofold (P<0.0001). CONCLUSION: Using a timesheet significantly reduced CIT to the shortest in France. The timesheet is an indicator of motivation and requires the collaboration of all transplantation personnel. It identified certain habits that may be improved to minimize CIT without reorganizing the unit. Providing quicker access to the operating room should further reduce CIT, the key to better graft survival. PMID- 17353775 TI - Pulmonary function in patients with type 1 diabetes before and after simultaneous pancreas and kidney transplantation. AB - INTRODUCTION: Pulmonary function is impaired in type 1 diabetes mellitus and is associated with the quality of metabolic control. Correction of chronic hyperglycemia by pancreas transplantation may ameliorate pulmonary function. METHODS: Lung volume and diffusing capacity were measured in 75 uremic patients with type 1 diabetes and a long diabetes duration waiting for a simultaneous kidney and pancreas transplantation (SPK). In addition 85 patients after SPK and 20 patients after kidney transplantation alone (KA) were investigated. In a subgroup of 30 patients, data before and after SPK were available for prospective analysis. RESULTS: Reduced lung volume and diffusing capacity were found in type 1 diabetic patients before transplantation. Nearly all parameters of pulmonary function improved after SPK and KA. A significant change was found for forced expiratory volume at 1 sec (FEV1) and FEV1/forced vital capacity (FVC) (Tiffenau index). A significant amelioration of diffusing capacity was only found in the SPK group but not in the KA group. The prospective investigation revealed significant improvements of pulmonary function after SPK: FEV1 (P=0.001), FVC, (P=0,006), Tiffenau index (P=0.03), and Hb-corrected diffusing capacity (carbon monoxide transfer factor, TCO), P=0.03; transfer coefficient (KCO=TCO corrected for alveolar volume), P=0.01. CONCLUSION: Simultaneous pancreas and kidney transplantation is able to attain long-term normoglycemia and to improve pulmonary function in uremic type 1 diabetic patients. PMID- 17353776 TI - Mycophenolate mofetil may allow cyclosporine and steroid sparing in de novo heart transplant patients. AB - BACKGROUND: Mycophenolate mofetil (MMF) provides superior prophylaxis against acute rejection when compared with azathioprine (AZA) in heart and renal transplantation. However, it remains unclear whether this results in improved survival or reduced morbidity after heart transplantation. METHOD: In a sequential study, 240 cardiac transplant patients were treated with either MMF (n=119) or AZA (n=121) both in combination with cyclosporine and corticosteroids after rabbit antithymocyte globulin induction. RESULTS: By protocol lower cyclosporine levels were targeted in the MMF group during the first year (e.g. 203+/-52 ng/mL MMF vs. 236+/-59 ng/mL AZA, P=0.0006 at 6 months). Patient survival at 1 year (82% MMF vs. 79% AZA, P=0.55) and at 3 years was similar in both groups. The cumulative probability of receiving antirejection treatment within 1 year was lower in the MMF group, as was biopsy-proven acute rejection with International Society of Heart and Lung Transplantation grade > or =3A (24% vs. 35%, P=0.03). The MMF group also had fewer episodes requiring cytolytic therapy (6% vs. 13%, P=0.04) and more patients had steroids withdrawn by 1 year (66% vs. 32%, P<0.001). Renal function was better in the MMF group with lower creatinine levels at 1 year (133+/-45 vs. 155+/-46 micromol/L, P=0.0004). Calculated creatinine clearance (Cockcroft and Gault formula) at 1 year was also better (MMF 74+/-32 mL/min vs. AZA 62+/-24 mL/min, P=0.004). CONCLUSION: Our results suggest that immunosuppression with MMF rather than AZA may allow lower cyclosporine levels, better renal function, and increased steroid weaning at 1 year while also achieving better control of acute rejection. PMID- 17353777 TI - Sparing effect by montelukast treatment for chronic graft versus host disease: a pilot study. AB - BACKGROUND: Chronic graft versus host disease (GvHD) is a major complication after allogeneic stem cell transplantation (SCT), which is usually progression from acute GvHD. Chronic GvHD is the main cause of severe morbidity and mortality in long-term survivors after SCT. The cysteinyl leukotrienes (cysLTs) and eosinophils play an important role in the pathogenesis of GvHD, which is the rationale for the combined use of montelukast (Mk) in the treatment of this illness. METHODS: Mk was administrated to 19 eligible patients with refractory chronic GvHD, in addition to their standard immunosuppressive regimens. Mk was given orally (10 mg once daily) for a mean period of 10 months (range, 2-21 months). Organ-specific response was determined by the new scoring criteria established by the National Institutes of Health consensus project. RESULTS: Based on organ involvements endpoints, overall response to the combined therapy with Mk was observed in 15 of 19 (79%) patients. Significant improvement of skin liver and gastrointestinal was observed in 53%, 62%, and 46%, respectively. Generally, Mk was notably beneficial in milder stages of GvHD, which lead to earlier withdrawal of other immunosuppressive agents. Side effects of Mk administration were not documented, nor were cases of relapse of the basic disease. CONCLUSIONS: Our preliminary prospective investigation supports the potential efficacy of Mk as a safe and toxicity-sparing supplement to standard therapy for patients with chronic GvHD. Future clinical studies are necessary to establish the optimal dose of Mk and its role in the symptomatic and prophylactic treatment of acute and chronic GvHD. PMID- 17353778 TI - Randomized study comparing cyclosporine with azathioprine one year after renal transplantation-15-year outcome data. AB - BACKGROUND: The introduction of cyclosporine (CsA) improved 1-year graft survival and reduced the incidence of acute rejection episodes after renal transplantation compared to azathioprine (Aza). However, CsA has many side effects and reducing exposure of this drug after the first year may benefit long-term patient and graft survival. METHODS: We report 15-year outcome data from a single center, randomized controlled study comparing CsA withdrawal and conversion to Aza with continuation of CsA 1-year posttransplant. RESULTS: Two hundred sixteen patients who showed a serum creatinine less than 300 mumol/L with no acute rejection episodes in the preceding 6 months were enrolled (CsA 114, Aza 102). There was no difference in patient survival at 15 years: 62.4% in the CsA group and 64.4% in the Aza group (P=0.6). Fifteen-year transplant survival was 41.9% for the CsA group and 48.8% for the Aza group (P=0.8). Fifteen-year graft survival censoring for death with a functioning graft was 58% in the CsA group and 72% in the Aza group (P=0.5). Predictors of patient survival were younger recipient age (P<0.001) and lower systolic blood pressure at randomization (P=0.01). Predictors of graft survival were older recipient age (P<0.001) and better renal function at randomization (P=0.01). Assigned drug showed no effect on graft or patient survival. Patients assigned to CsA showed significantly worse renal function up to 10 years posttransplantation and required more anti-hypertensive treatment throughout the study period. CONCLUSION: In a selected group of patients, either Aza or low-dose CsA is safe and effective. Despite lower estimated glomerular filtration rate (eGFR) up to 10 years posttransplantation and increased use of anti-hypertensive agents, low-dose CsA was not associated with a worse patient or graft survival. PMID- 17353780 TI - Donor factors influencing graft outcomes in live donor kidney transplantation. AB - Living donor renal allograft survival is superior to that achieved from deceased donors, although graft outcome is suboptimal in some of these patients. In an effort to identify the subset of patients at high risk for poor outcomes we studied donor risk factors in 248 living kidney donor-recipient pairs. Unadjusted donor (125)I-iothalamate GFR (iGFR), donor age more than 45 years, donor total cholesterol level less than 200 mg/dL, and donor systolic blood pressure (SBP) less than 120 mm Hg were correlated with allograft estimated glomerular filtration rate (eGFR), and incidence of acute rejection (AR), delayed graft function and/or graft loss at 2 years posttransplantation. Donor iGFR less than 110 mL/min (slope=-7.40, P<0.01), donors more than 45 years (slope=-8.76, P<0.01), donor total cholesterol levels more than 200 mg/dL (slope=-10.03, P<0.01), and SBP more than 120 mm Hg (slope=-5.60, P=0.03) were associated with lower eGFR. By multivariable linear regression analysis these variables remained independently associated with lower eGFR, and poorer outcomes. The increasing number of donor factors (age, iGFR, cholesterol, and blood pressure) was directly associated with worse posttransplant eGFR (P<0.01). In conclusion, our data suggest that routine assessment of living donor parameters could supplement the consideration of recipient characteristics in predicting posttransplant risk of graft injury/dysfunction. PMID- 17353779 TI - Combination of extended donor criteria and changes in the Model for End-Stage Liver Disease score predict patient survival and primary dysfunction in liver transplantation: a retrospective analysis. AB - BACKGROUND: The purpose of this study was to analyze the impact of extended donor criteria (EDC) and of changes in the Model for End-Stage Liver Disease (MELD) score while waiting for liver-transplantation (Delta-MELD) on patient survival and initial graft function. METHODS: We included 386 consecutive patients with end-stage liver disease who underwent orthotopic liver transplantation at the Medical University Vienna between 1997 and 2003. Primary outcome was patient survival and secondary outcome was initial graft function. EDC included: age >60 years, >4 days intensive medical care, cold ischemia time >10 hr, need for noradrenalin >0.2 microg/kg/min or doputamin >6 microg/kg/min, a donor peak serum sodium >155 mEq/L, a donor serum creatinine >1.2 mg/100 mL, and a body mass index >30. RESULTS: Delta-MELD was significantly higher in the nonsurvivor population (P=0.01) and EDC showed a significant influence on initial graft function (P=0.01). Worsening in either Delta-MELD or the presence of at least two EDC was not associated with an increased risk of primary graft dysfunction and death. Worsening in Delta-MELD and the presence of at least two EDC was significantly associated with primary graft dysfunction (P=0.01) and death (P=0.008). CONCLUSION: The combination of a liver recipient with worsening Delta-MELD and a potential donor with at least two EDC should be avoided. PMID- 17353781 TI - Living donor kidney transplantation: the effects of donor age and gender on short and long-term outcomes. AB - BACKGROUND: The influence of donor age and sex on acute rejection episodes and short- and long-term graft survival in living donor (LD) kidney transplantation has not been well characterized. METHODS: This prospective cohort study includes 739 first time LD transplantations with median follow-up time of 55.1 months. Death censored graft survival according to donor age and sex was compared with Kaplan-Meier plots. Cox regression was performed to estimate the association between different risk factors and graft survival and acute rejection episodes. RESULTS: Graft survival was not affected by donor age above 50 years as long as these recipients did not experience an early acute rejection episode. Acute rejection episodes increased in recipients of grafts from donors > or =65 years (P=0.009). Donor age > or =65, recipient age less than 50 years, human leukocyte antigen (HLA)-DR matching, and female donor gender were risk factors for early acute rejection episodes. In multivariate analysis donor age > or =65 years was a risk factor for graft loss in all time periods after transplantation. During the first 5 years after transplantation a steroid resistant rejection episode was an additional risk factor. More than 5 years after transplantation male donor gender was the only additional risk factor for graft loss. CONCLUSION: These results support the continued use of older male and female living donors who meet carefully constructed medical criteria and who are highly motivated to donate. Furthermore, donor age seems to be a more important predictor of graft loss than donor sex. PMID- 17353782 TI - Mycophenolate mofetil inhibits tumor growth and angiogenesis in vitro but has variable antitumor effects in vivo, possibly related to bioavailability. AB - BACKGROUND: Identifying immunosuppressive agents with antitumor effects could help address the problem of posttransplant malignancy. Here we tested for potential inhibitory effects of mycophenolate mofetil (MMF) on tumors in vitro and in vivo. METHODS: Mouse CT26 colon adenocarcinoma, B16 melanoma, and human TMK1 gastric adenocarcinoma cells were tested for in vitro growth in the presence of MMF. In vitro angiogenesis was tested with a rat aortic-ring assay. Tumor cells were implanted into dorsal skinfold chambers (DSFC) to assess in vivo angiogenesis. Subcutaneous tumor growth was determined in mice receiving MMF. RESULTS: MMF caused a dose-dependent reduction in tumor cell numbers in vitro, starting between 0.1 to 1 microM. Vessel sprouting from aortic rings was markedly blocked by similar concentrations of MMF. In vivo, however, DSFC results showed a marginal reduction in CT26 tumor angiogenesis with MMF doses of 40 or 80 mg/kg/day, although MMF did inhibit TMK1 vascularity. Moreover, 80 mg/kg/day MMF did not reduce subcutaneous CT26 tumor volumes, but did slightly inhibit B16 and TMK1 expansion. Interestingly, the mycophenolic acid (MPA) blood level 2 hr after 80 mg/kg/day MMF bolus dosing was near 14 mg/L, but decreased dramatically thereafter, suggesting a drug availability issue. Indeed, intermittent 2-hr MMF pulses in tumor-cell cultures substantially reduced the antiproliferative effect of MPA. CONCLUSION: MMF strongly inhibits tumor cell growth and angiogenesis in vitro, but only marginally inhibits tumors in vivo. These contrasting results may relate to drug availability, where intermittent exposure of tumor cells to immunosuppressive doses of MMF substantially reduce its potential antitumor effects. PMID- 17353783 TI - Requirement of MyD88 for macrophage-mediated islet xenograft rejection after adoptive transfer. AB - BACKGROUND: Porcine antigen primed and CD4+ T-cell activated macrophages are able to migrate to and destroy porcine xenografts. However, the specific signaling mechanisms involved remain to be identified. METHODS: In this study macrophages which lack the universal toll-like receptor (TLR) adaptor MyD88 were used to investigate the role of TLR in the recognition and activation of macrophages in islet xenograft rejection. Macrophages were isolated from rejecting MyD88(-/-) and wild-type C57BL/6 mice that were recipients of neonatal porcine pancreatic cell cluster (NPCC) xenografts, and were transferred to NPCC recipient NOD-SCID mice. RESULTS: Both wild-type C57BL/6 and MyD88(-/-) mice rejected NPCC xenografts 8 and 10 days, respectively after transplantation, and the grafts were heavily infiltrated with CD4+ T cells and macrophages. However, graft infiltrating macrophages from rejecting MyD88(-/-) recipients demonstrated impaired up-regulation of TLR expression and impaired activation phenotype, when compared to those from rejecting C57BL/6 recipients. Transfer of NOD-SCID recipients with macrophages from rejecting C57BL/6 mice resulted in NPCC xenograft rejection along with massively infiltrated macrophages 8 days after transfer, whereas NPCC xenografts in NOD-SCID mice transferred with macrophages from rejecting MyD88(-/-) mice remained intact until the end of this study, 90 days after transfer, with insulin-positive islets and no infiltration by macrophages. CONCLUSION: This study demonstrates that deletion of MyD88 causes impaired macrophage activation after pig islet xenotransplantation. However, graft survival is not prolonged and xenografts are rejected rapidly by alternate mechanisms. PMID- 17353784 TI - Limited contribution of cells of intact extrahepatic tissue origin to hepatocyte regeneration in transplanted rat liver. AB - BACKGROUND: It is now well established that various adult somatic tissues harbor multipotent stem cells that can differentiate into a broad variety of cell types of all three germ layer origins. It remains controversial, however, whether they are a reservoir of cells utilized for emergent tissue repair or simply a vestige of evolution and, if the former is the case, to what extent they can potentially contribute to reconstitution of a specific organ. To get an insight in such a direction, we examined the extent of contribution of naive intact cells of extrahepatic origin to hepatocyte reconstitution in the transplanted liver with or without injury in the rat. METHODS: Liver from wild-type donor rats was transplanted to green fluorescent protein (GFP)-transgenic rats, and GFP-positive hepatocytes were examined with or without liver injury. RESULTS: The proportion of GFP-positive hepatocytes in the transplanted noninjured liver linearly increased by 0.0048% per week, that is, approximately 5 x 10(3) hepatocytes of extrahepatic origin were generated per day. Liver injury induced by treatment with 2-acetylaminofluorene and CCl4 or the additional application of hepatocyte growth factor did not further increase the percentage of GFP-positive hepatocytes. CONCLUSION: The present results indicate that cells derived from nonmanipulated extrahepatic tissues appreciably contribute, though limitedly, to hepatocyte reconstitution in the liver of the rat. PMID- 17353785 TI - Rapamycin promotes emergence of IL-10-secreting donor lymphocyte infusion-derived T cells without compromising their graft-versus-leukemia reactivity. AB - BACKGROUND: There are limited data examining the effects of pharmacological immunosuppression on the in vivo fate of donor lymphocyte infusions (DLI)-derived T cells, their function, and their antitumor efficacy. METHODS: We addressed this question in a murine model in which DLI is given to stable mixed chimeras resulting in lymphohematopoietic graft-versus-host (LH-GVH) response. In this model, LH-GVH potency can be directly measured as the kinetics of conversion to full donor chimerism and can be correlated with associated graft-versus-leukemia (GVL) reactivity. RESULTS: We found discordance in DLI-mediated LH-GVH reactivity depending on the timing of rapamycin (RAPA) administration. Delayed administration of RAPA in contrast to its early administration at the time of adoptive transfer did not interfere with conversion to full donor chimerism. Moreover, delayed administration of RAPA preserved the GVL reactivity of DLI. Analysis of the long-term chimeras showed that regardless of RAPA administration, adoptively transferred T cells mediating the LH-GVH response contribute minimally to the reconstitution of the peripheral T-cell compartment and exhibit profound hyporesponsiveness and decreased production of interleukin (IL)-2 on restimulation in vitro. However, we observed only in the RAPA-treated chimeras that the remaining hyporesponsive DLI-derived CD4+ T cells secrete large amounts of IL-10, a known immunoregulatory cytokine. CONCLUSIONS: We conclude that delayed administration of RAPA after DLI does not interfere with their LH-GVH reactivity but promotes the emergence of IL-10-secreting DLI-derived CD4+ T cells that might contribute to the drug's known ability to promote bilateral donor host tolerance without interfering with GVL reactivity. PMID- 17353786 TI - Is cystatin C useful for the detection and the estimation of low glomerular filtration rate in heart transplant patients? AB - Although previously studied in patients with chronic kidney disease, there is less data for the use of cystatin C and cystatin C-based formulas in heart transplant recipients. The ability of creatinine and cystatin C to detect renal failure (glomerular filtration rate [GFR] below 60 mL/min/1.73 m(2)) in heart transplant patients has been compared. The accuracy and precision of a creatinine based formula (Modification of Diet in Renal Disease [MDRD]) versus a cystatin C based formula (Rule's formula) to estimate GFR have also been studied. GFR was measured using the (51)Cr-ethylenediamine tetraacetic acid tracer in 27 patients. There was no significant difference between GFR and the reciprocal of creatinine or cystatin C. Receiver operating characteristic curves for cystatin C and creatinine were similar. Both formulas were well correlated with the GFR. The bias of the cystatin C-based was significantly better than one of the MDRD formula, but the standard deviation appeared better for the MDRD formula (bias of +3.9 mL/min/1.73 m(2) versus +12 mL/min/1.73 m(2) and SD of 8.5 versus 11.6, respectively). Plasma cystatin C has no clear advantage over serum creatinine to detect renal failure in heart transplanted patients. PMID- 17353787 TI - Impact of long-term therapy with FTY720 or mycophenolate mofetil on cardiac conduction and rhythm in stable adult renal transplant patients. AB - The novel immunomodulator FTY720 has been associated with a mild reduction in heart rate (HR) in clinical trials. A total of 421 patients (FTY720, n=94; mycophenolate mofetil [MMF], n=327) underwent 2-day electrocardiogram and 24-h Holter monitoring. Patients had been maintained on cyclosporine plus MMF or FTY720 (2.5 mg and 5.0 mg) for > or =12 months. No significant differences in mean hourly heart rate (HR) over 24 hrs were noted between groups. Bradycardia (HR 35-50 bpm) and sustained bradycardia (HR <50 bpm for >1 min) were more common with MMF than FTY720 (53% vs. 37% and 34% vs. 21%, respectively). Electrocardiogram parameters did not differ significantly between FTY720 and MMF groups, or between FTY720 groups, supporting the absence of a dose-dependent effect. The absence of any clinically significant effect of FTY720 on cardiac rhythm demonstrates that the reduction in HR seen after the first dose does not persist in the maintenance phase. PMID- 17353788 TI - Immunophenotype of infiltrating cells in protocol renal allograft biopsies from tacrolimus-versus cyclosporine-treated patients. AB - The prevalence of subclinical rejection is lower in patients receiving tacrolimus than in patients treated with cyclosporine. However, it is not known whether this difference is related to the modulation of a specific cell immunophenotype. We perform a two case-one control study in patients treated with tacrolimus (n=44) or cyclosporine (n=22) with a protocol biopsy performed at 4 to 6 months. Immunophenotype of infiltrating cells was evaluated with monoclonal antibodies directed against CD45 (all leukocytes), CD3 (T lymphocytes), CD68 (monocytes/macrophages), and CD20 (B lymphocytes) and expressed as interstitial positive cells/mm(2). The number of interstitial CD45 (290+/-209 vs. 696+/-560; P<0.01), CD3 (121+/-84 vs. 208+/-104; P<0.01), and CD68 (155+/-232 vs. 242+/-280; P<0.05) but not CD20 (137+/-119 vs. 197+/-154) positive cells was lower in tacrolimus-treated patients. T lymphocytes and macrophages interstitial infiltration was reduced in tacrolimus treated patients evaluated with protocol biopsies in comparison to cyclosporine-treated patients. PMID- 17353789 TI - Blockade of the passive cell death pathway does not prevent tolerance induction to islet grafts. AB - BACKGROUND: T-cell apoptosis is an important regulatory mechanism in transplant tolerance. The aim of this study was to identify specific apoptotic molecules important for tolerance induction. METHODS: Mice expressing the human Bcl-2 molecule in T cells or Bim -/- mice were used as islet allograft or rat islet xenograft recipients and treated with CTLA4-Fc and MR1 costimulation blockade. RESULTS: hBcl-2 transgenic mice and Bim -/- accepted islet allografts and rat islet xenografts for more than 100 days, similar to wildtype controls. Changes in the dose of the CTLA4-Fc and MR1 did not lead to differences in graft survival and there were no differences in the percentage of CD4+ T cells expressing Fas, CD25, or undergoing apoptosis. CONCLUSIONS: Inhibition of the passive cell death pathway in T cells did not block tolerance induction, suggesting that the mechanism by which apoptosis regulates the alloimmune response is more complex than first thought. PMID- 17353790 TI - Growth factor-induced mobilization of dendritic cells in kidney and liver of rhesus macaques: implications for transplantation. AB - Hematopoietic growth factors (HGF) mobilize potential tolerogenic cells in transplant donors. Fms-like tyrosine kinase 3 ligand (Flt3L) mobilizes stem cells and dendritic cells (DCs) in human and nonhuman primate blood. Blood and renal and liver biopsies were obtained from untreated and Flt3L-mobilized rhesus macaques. Flt3L increased the number of myeloid CD11c(hi) and plasmacytoid CD123(hi) precursors in blood and both myeloid CD11c(+) HLA-DR(+) fascin(+) (CD45RA(-)) DCs and putative plasmacytoid CD11c(lo) CD45RA(hi) DC precursors in liver and kidneys, without affecting organ function. DC in Flt3L-treated monkeys were concentrated in the glomeruli and interstitium of kidneys, and in the portal triads and parenchyma of liver. These DCs exhibited the phenotype of immature antigen-presenting cells (APCs; CD83(-) CD86(lo) CCR5(+) CCR7(-)). HGF-induced changes reversed significantly within 7 days of Flt3L withdrawal. Therapeutic protocols that mobilize donor hematopoietic cells should consider the influence of HGF on the APC constituency of prospective organ allografts. PMID- 17353791 TI - CTLA4Ig promotes the induction of hematopoietic chimerism and tolerance independently of Indoleamine-2,3-dioxygenase. AB - Bone marrow transplantation (BMT) under costimulation blockade induces mixed chimerism and tolerance in rodent models. Recent data, predominantly from in vitro studies, suggest that in addition to blocking the CD28 costimulation pathway CTLA4Ig also acts through upregulating the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). Here we demonstrate that even though CTLA4Ig is critically required for the induction of chimerism and tolerance in a murine model of nonmyeloablative BMT, IDO activity is not. No significant differences were detectable in the kynurenine to tryptophan ratios (indicative of IDO activity) in sera of BMT recipients treated with CTLA4Ig (tolerant group) versus BMT recipients treated without CTLA4Ig (nontolerant group) versus naive controls. In vivo inhibition of IDO immediately after BMT with CTLA4Ig or several months thereafter did not block achievement of chimerism and tolerance. Thus, IDO does not play a critical role in the induction or maintenance of chimerism and tolerance in a CTLA4Ig-based BMT model. PMID- 17353792 TI - Nonserogroup O1 Vibrio cholerae in a renal transplant patient. PMID- 17353793 TI - Hepatic artery-portal venous fistula after percutaneous intraportal islet cell transplant. PMID- 17353794 TI - Orthopaedic, radiology, pathology conference: Ankle pain in a 31-year-old man. PMID- 17353795 TI - Distal tibial osteoarticular allografts. AB - Osteoarticular allografts can be used for limb reconstruction following tumor excision. Most commonly, the distal femur, proximal tibia and distal radius have been studied, while distal tibial allografts receive only sporadic mention in the literature. We evaluated the functional outcomes of distal tibial allografts used in tumor reconstruction. Following FDA guidelines and using a questionnaire, we surveyed operating surgeons on the outcomes of 29 distal tibial allografts used to reconstruct osseous defects secondary to benign and malignant tumors. Twelve patient questionnaires were returned revealing nine complications in eight patients. These included nonunions (three), fracture (two), arthrosis (two), and delayed union (two). There were no reported infections. Two patients died of their disease. The average rating using the Musculoskeletal Tumor Society (MSTS) score was 67.3%. The 10 living patients had an average rating of 72.4%. Distal tibial osteoarticular allografts offer acceptable functional results when used in tumor reconstruction. Difficulties achieving union (delayed or nonunion) between the host and the graft appears the most common complication of this technique. PMID- 17353796 TI - Segmental tibia fractures: a prospective evaluation. AB - Debate exists regarding the treatment of segmental tibia fractures. We report a large series of segmental fractures treated with a single technique of nonreamed nailing and report the time to union, reoperation rate, and associated complications. Emphasis was placed on achieving an anatomic reduction with good interfragmentary contact. We prospectively followed 62 consecutive patients with closed and open segmental tibia fractures (Orthopaedic Trauma Association Type 42 C2). Three patients died and eight were lost to followup, leaving 51 patients followed to union. Forty-six of the 51 fractures (91%) united with one operation (average time to union 138 days in closed fractures and 178 days in open fractures). Five patients had secondary procedures before achieving union. Type 3B fractures and those associated with compartment syndrome had the longest time to union, averaging 294 days. Full weightbearing was achieved within 3 months for all closed fractures and 74% of open fractures. There were no deep infections or nail or screw breakages in the series and knee pain occurred in 14 patients (27%). Nonreamed nailing is associated with high union rates, few complications, and limited indications for secondary procedures in the management of segmental tibia fractures. PMID- 17353797 TI - Children with fractures show higher levels of impulsive-hyperactive behavior. AB - Children with fractures have been reported to have impulsive-hyperactive behavior problems although whether they exhibited such behavior more often than children with other orthopaedic conditions is unknown. We investigated whether impulsivity hyperactivity was more prominent in children with extremity fractures than in children with orthopaedic conditions not involving a fracture. From outpatient clinical intakes, we recruited 39 consecutive children with extremity fractures and 33 children with orthopaedic conditions not involving a fracture. We used the Conners' Parent Rating Scale to detect behavioral symptoms in children with and without extremity fractures. Children who were treated for extremity fractures had higher mean scores for impulsivity-hyperactivity than those treated for nontrauma-related reasons. Additionally, more children in the fracture group reached impulsive-hyperactive behavior scores high enough to warrant additional psychiatric evaluation. In terms of injury prevention, the orthopaedic surgeon should be familiar with problem behaviors of children, particularly impulsivity and hyperactivity, to be able to make appropriate referrals for psychiatric evaluation and treatment. PMID- 17353798 TI - Thinner plantar fascia predicts decreased pain after extracorporeal shock wave therapy. AB - Increased plantar fascia thickness is common with chronic plantar fasciitis, and reduction of the thickness after extracorporeal shock wave therapy or steroid injection has been reported. We hypothesized a decrease of plantar fascia thickness was associated with pain reduction after extracorporeal shock wave therapy. Fifty-three eligible patients with 78 symptomatic feet were randomly treated with piezoelectric-type extracorporeal shock wave therapy of two intensity levels (0.12 and 0.56 mJ/mm2). Two thousand shock waves for three consecutive sessions were applied at weekly intervals. A visual analog scale for pain, the Foot Function Index, the Short Form-36 Health Survey, and ultrasonographic measurement of plantar fascia thickness were evaluated at baseline and 3 and 6 months after treatment. We analyzed the association between pain level and plantar fascia thickness with generalized estimating equation analysis and adjusted for demographic and treatment-related variables. Patients with thinner plantar fascia experienced less pain after treatment; high-intensity treatment and regular exercise were associated with lower pain level. The overall success rates were 63% and 60% at the 3- and 6-month followups. High- and low intensity treatments were associated with similar improvements in pain and function. Receiving high-intensity treatment, although associated with less pain at followup, did not provide a higher success rate. PMID- 17353799 TI - The 2007 ABJS Marshall Urist Award: The impact of direct-to-consumer advertising in orthopaedics. AB - Direct-to-consumer advertising (DTCA) has become an influential factor in healthcare delivery in the United States. We evaluated the influence of DTCA on surgeon and patient opinions and behavior in orthopaedics by surveying orthopaedic surgeons who perform hip and knee arthroplasties and patients who were scheduled to have hip or knee arthro-plasty. Respondents were asked for their opinions of and experiences with DTCA, including the influence of DTCA on surgeon and patient decision making. Greater than 98% of surgeon respondents had experience with patients who were exposed to DTCA. The majority of surgeon respondents reported DTCA had an overall negative impact on their practice and their interaction with patients (74%), and their patients often were confused or misinformed about the appropriate treatment for their condition based on an advertisement (77%). Fifty-two percent of patient respondents recalled seeing or hearing advertisements related to hip or knee arthroplasty. These patients were more likely to request a specific type of surgery or brand of implant from their surgeon and to see more than one surgeon before deciding to have surgery. Direct to-consumer advertising seems to play a substantial role in surgeon and patient decision making in orthopaedics. Future efforts should be aimed at improving the quality and accuracy of information contained in consumer-directed advertisements related to orthopaedic implants and procedures. PMID- 17353800 TI - What is quality of life in children with bone sarcoma? AB - Quality of life measures have neglected to include a critical self-assessment component in pediatric sarcoma patients. Our report shows how children rate their own quality of life and how that varies over time after surgery. Using the Pediatric Outcomes Data Collection Instrument, quality of life data was prospectively collected and combined with a retrospective review of clinical parameters on 43 children with primary bone sarcoma, with an average followup of 3 years. Children reported good yet variable scores in five of the six domains. Lower scores were noted in the Sports/Physical Functioning domain, particularly in the first 12 months after surgery, with improvement seen up to 24 months after surgery. Tumor specific factors such as size larger than 8 cm and lower extremity location were negative predictors for Sports/Physical Functioning. The only demographic factor that predicted perceived quality of life scores was gender, with girls reporting lower scores in Sports/Physical Functioning, Pain/Comfort, and Global Functioning domains. The Pediatric Outcomes Data Collection Instrument gives discriminatory detailed textured evaluation of the outcome of children treated for skeletal sarcoma. Further development of quality of life measures is needed to allow its use in treatment selection. PMID- 17353801 TI - ACL impingement prediction based on MRI scans of individual knees. AB - Although tibial external rotation and abduction do not load the ACL strongly in cadaver-based biomechanical studies, such knee positions are associated with ACL injuries in clinical practice. We hypothesized the ACL could be injured in such knee positions because of its impingement against the intercondylar notch. We developed a three-dimensional geometric ACL impingement model through segmentation of MR images of individual knees. We investigated impingement by determining the deformed geometry and elongation of the ligament as it wrapped around the notch surface during impingement. When impingement did not occur, the gap width separating the ligament and the notch surface was computed. Tibial external rotation/abduction could cause the ACL to impinge against the lateral notch wall and elongate as it wraps around the surface of the notch wall. The impingement occurred between the middle portion of the ligament (at 45% +/- 8% [mean +/- standard deviation] of the ligament length) and the convex surface of the lateral notch wall. Considering the multiband fiber architecture of the ligament, the anteromedial band of the ACL sustained greater elongation during impingement and showed a smaller gap width from the notch surface than the intermediate band or the posterolateral band. PMID- 17353802 TI - Ezrin expression predicts survival in stage IIB osteosarcomas. AB - Ezrin, a cytoskeleton linker protein, has been reported to be involved in the metastasis of solid tumors in animal models and patients in small clinical studies. We analyzed the relationship between immunohistochemical expression of ezrin and the prognosis of osteosarcoma. We retrospectively identified 64 patients with Stage IIB osteosarcomas between 1995 and 2000. Tissue microarrays were constructed from incisional biopsy specimens and immunohistochemical staining was performed. Ezrin expression and other clinicopathologic variables such as age, gender, pathologic subtype, tumor size and location, and histologic response were compared with outcomes. The minimum followup was 12 months (mean, 78.2 months; range, 12-137 months). Twenty-three of 64 patients (35.9%) showed late distant metastasis; 33 of 64 patients (51.6%) showed expression of ezrin, and of these 33 patients, 22 (66.7%) had distant metastasis develop. Multivariate analysis revealed histologic response to preoperative chemotherapy and expression of ezrin predicted disease-free survival. Expression of ezrin in osteosarcoma biopsy specimens is promising as a marker to predict outcome in patients with osteosarcoma. PMID- 17353803 TI - Postmenopausal hormone therapy in clinical perspective. AB - Although many of the risks and benefits of postmenopausal hormone therapy are known, only recently has the magnitude of these effects and their perspective to other therapies become more fully understood. Careful review of randomized controlled trials indicates that the risks of postmenopausal hormone therapy including breast cancer, stroke and venous thromboembolism are similar to other commonly used agents. Overall, these risks are rare (less than 1 event per 1,000 women) and even rarer when initiated in women less than 60 years of age or within 10 years of menopause. In addition, the literature indicates similar benefit of postmenopausal hormone therapy, in women who initiate hormone therapy in close proximity to menopause, to other medications used for the primary prevention of coronory heart disease in women. PMID- 17353805 TI - Community nurses and self-management of blood glucose. AB - Self-monitoring of blood glucose (SMBG) is commonly recommended to patients with diabetes, although the rationale for this is unclear. This small research project was designed to explore the reasons why nurses working in the community recommend SMBG. Seven interviews were carried out with community nurses caring primarily for housebound patients. Those interviewed believed that a sound evidence-base supported the recommendation that patients test their blood, but not urine, for glucose levels. Though nurses believed in the importance of patient choice and empowerment, the scope for these was limited among housebound patients. There was no evidence that patients understood how to respond to test results, or that comprehensive care planning was normal practice. Although small, this study suggests that nurses working in community settings may need to update their knowledge. It also suggests that a national debate is necessary to disseminate better the evidence about SMBG, and its implications for nursing practice. PMID- 17353806 TI - Engaging women from South Asian communities in cardiac rehabilitation. AB - This study sought to describe experiences and perceptions of cardiac rehabilitation among a sample of women from South Asian communities. Data were collected via eight semi-structured interviews with staff and a focus group discussion with nine clients from a community-based, culturally sensitive cardiac rehabilitation service. A number of individual, cultural and practical barriers to participation were identified. Facilitators centred on whether the format and content of the sessions could be considered "appropriate". For example, a women's dance group proved to be successful through the selection of a familiar local venue, supportive session leader, and activity that was felt to be both enjoyable and beneficial. This study has shown that it is possible to engage hard-to-reach groups in cardiac rehabilitation and physical activity. Further work is needed to explore whether this research is applicable in other ethnic groups and whether the lessons learned could be successfully incorporated into mainstream health services. PMID- 17353807 TI - Developing education for long-term conditions management. AB - This article discusses the experience of one university in the development, implementation and evaluation of a modular programme of study for practitioners working with people with long-term conditions. It addresses the complexity of developing a curriculum in response to Department of Health initiatives, at times pre-empting central guidance. It highlights the importance of partnership working underpinning every aspect of programme development. The article provides some context for the policy initiative, discusses some of the challenges in programme design, content and the requirement for work-based learning. The assessment, learning and teaching strategies are described, highlighting some of the benefits of portfolios as a means of evidencing and enhancing learning. Evaluation and progress of the programme to date is shared, highlighting some future challenges. This includes ensuring that the programme continues to complement other courses and that modules meet future challenges, including the Nursing and Midwifery Council requirements for advanced practice. PMID- 17353808 TI - A deadly harvest: the effects of cold on older people in the UK. AB - Excess winter mortality of some thousands of deaths of older people has occurred in the UK for the past 150 years and shows only moderate abatement. Government policies in both health and social care have had little apparent effect, other than a slow decline in seasonality due largely to secular trends. There are a number of apparent misconceptions, commonly held in the public mind and subsumed in public policy, which need to be corrected in order to reduce the toll of winter cold on older people. The evidence shows that winter deaths are to a large extent avoidable. They are not due to hypothermia as is widely believed, may not be necessarily reduced by climate change in the foreseeable future and may only be partially reduced by improving indoor warmth alone. The key is an integrated policy which reduces all risks equally. Community nursing is well placed to play a pivotal role in such policies. PMID- 17353809 TI - Supporting practice teachers to identify failing students. AB - The subject of identifying and supporting failing students in community nursing education programmes has been largely overlooked in the literature, yet is of great concern to practice teachers. This article discusses the views on the topic of a group of practice teachers in the light of existing, related research and proposes a number of indicators for good practice. It is suggested that of central importance is the need for higher education institutions and practice teachers to work together in identifying students causing concern at an early stage in their studies, based on both objective and subjective observations, and to have in place documented procedures to be followed when such situations arise. PMID- 17353810 TI - Work-related stress, work/life balance and personal life coaching. AB - Work-related stress adversely affects personal performance, organizational efficiency and patient care as well as costing the NHS millions of pounds each year. Reducing the effects of work-related stress is a legal duty for all employers. There are a number of resources available to help both employees and employers, such as the Health and Safety Executive stress management standards. Personal life coaching is one approach to reducing work-related stress, which is well established amongst business and management executives as well as some public sector organizations. PMID- 17353811 TI - A district nurses' guide to disability discrimination law: part 1. AB - District nurses have a unique role in the continuing care of people with disabilities. Some 20% of people are considered disabled and they now have rights under the Disability Discrimination Act 1995. However, to benefit from these rights people must meet the legal definition of disabled under the Act. It is essential therefore that district nurses are able to interpret and apply this legal definition in relation to their patients in order to better advise them regarding their disability and their rights under the Act. In the first of two articles on disability discrimination, Richard Griffith and Cassam Tengnah discuss the requirements that need to be fulfilled in order to meet the definition of disabled under the Disability Discrimination Act 1995. PMID- 17353812 TI - Lessons from the Evercare evaluation. PMID- 17353814 TI - Is the modern NHS fit for nursing students? PMID- 17353815 TI - Lymphoedema: a female health issue with implications for self care. AB - Many women in the general population either have, or are at risk of developing, lymphoedema, which is an incurable but manageable life-long condition, which may have a devastating effect physically and emotionally. Factors that predispose women to develop lymphoedema are outlined in this article. Strategies to prevent or minimize the severity of lymphoedema are identified. The role of healthcare professionals in empowering women and promoting actions and attitudes that enable them to minimize the risk of developing lymphoedema or exacerbating established lymphoedema and facilitating coping are discussed. PMID- 17353816 TI - A multidisciplinary approach to self care in chronic pelvic pain. AB - Chronic pelvic pain is one of the most difficult conditions encountered by health professionals working with women both in primary and secondary care. The cause is variable, and for some women a diagnosis is never determined. While it is acknowledged that it is a symptom and not a condition, many women and professionals continue to seek a cause and cure. It is contended that this client group is best supported by a multidisciplinary approach to symptom control that incorporates the skills of the gynaecologist, physiotherapist, nurse, psychologist and pain management specialist. This is often difficult to achieve within a resource-limited environment. An alternative approach is suggested using current resources, which provides patient education and support, thus empowering women to influence their health behaviours and situations. PMID- 17353817 TI - Advanced breast cancer: aetiology, treatment and psychosocial features. AB - Breast cancer is a common form of cancer in women of varying age. Due to the relationship between breasts, sexuality and reproduction, this form of cancer has an interconnected psychological and psychosocial influence on the well-being of women. Current understanding of the aetiology and pathogenesis of the disease has evolved as evidence supporting a role for genes such as the HER2 gene has emerged. HER2-positive breast cancer is a particularly progressive form of the disease as a result of its ability to differentiate and spread. Trastuzumab (Herceptin) forms part of the current treatment for this form of breast cancer; albeit costly, it has been shown to improve survival rates in women. For this reason it is now a recommended treatment for early-stage breast cancer. During and after treatment cycles, the breast cancer nurse and medical practitioners should be available to provide emotional support and advice on the manifestations of the disease, coping strategies and how breast cancer patients manage close family relatives. PMID- 17353818 TI - Innovative computer-based learning for breast cancer surgery. AB - Discussions with student nurses when they have been on placement on the breast cancer surgery ward highlighted their lack of knowledge about breast cancer surgery. This lack of knowledge by student nurses necessitated the development of a computer-based learning tool. A distance-learning tool was found to be an effective way of providing education, due to lack of facilities and workload on the ward. The student nurses using this tool will have better understanding of the treatments their patients are undergoing, leading to improved patient care. PMID- 17353819 TI - Ostomy bag management: comparative study of a new one-piece closed bag. AB - The aim of this study was to compare the performance of a new one-piece closed ostomy bag, SenSura, to an already established bag with a focus on minimizing problems related to use of stoma bags for individuals with a colostomy. There were 68 Danish participants with a colostomy who tested each bag for 1 week in a randomized, open, comparative, crossover study. The SenSura bag was perceived more secure than the reference bag (p=0.0006). Crucial performance and safety parameters were rated significantly better for SenSura than for the reference bag. The high preference for SenSura (85%) reflected these results (p<0.0001). Individuals with a colostomy can expect a higher sense of security with the SenSura bag than with the reference bag. This may relate to good adhesion, tack, flexibility and effective filter performance. Future studies should examine the long-term effects of SenSura on peristomal skin conditions. To our knowledge, this is the first published comparative study of one-piece closed ostomy bags. PMID- 17353820 TI - Discovery of neuropathic pain following breast surgery. PMID- 17353821 TI - Part 3: Nurses' guide to alcohol and promoting healthy lifestyle changes. AB - In this the third and final part, the focus is on the support and care of patients who are working towards a solution for their drink problem. While a number of treatment regimens exist for the management of alcohol abuse and there are well established groups to assist patients and their families, this article concentrates on three critical themes. The first concerns the promotion of insight. Only when the drink problem is understood by patients, carers and professionals alike, and shared in common terms, can rehabilitation begin to work. The second concerns communication channels. The propensity of some patients to deny their problem, or to lapse from therapy, makes communication especially challenging. While some patients are helped to overcome the risk of lapsing by being segregated from their usual community for some time (the clinic approach), many less well-resourced patients must tackle this problem from home and with the help of community-based practitioners. Finally, the interplay of treatment (detoxification) and psychological support is discussed, arguing that the nurse has an important part to play in motivating patients and helping them to solve problems as they arise. PMID- 17353822 TI - The duty of care 2: risk assessment and risk management. AB - In this second article in the series, the issue of risk assessment and management, in the context of a recent case, is revisited. The case in question is outlined in the previous article 'Compliance with directives and protocols'. PMID- 17353823 TI - Literature review: should nursing take aromatherapy more seriously? AB - Aromatherapy is often misunderstood and consequently somewhat marginalized. Because of a basic misinterpretation, the integration of aromatherapy into UK hospitals is not moving forward as quickly as it might. Aromatherapy in UK is primarily aimed at enhancing patient care or improving patient satisfaction, and it is frequently mixed with massage. Little focus is given to the real clinical potential, except for a few pockets such as the Micap/South Manchester University initiative which led to a Phase 1 clinical trial into the effects of aromatherapy on infection carried out in the Burns Unit of Wythenshawe Hospital. This article discusses the expansion of aromatherapy within the US and follows 10 years of developing protocols and policies that led to pilot studies on radiation burns, chemo-induced nausea, slow-healing wounds, Alzheimers and end-of-life agitation. The article poses two questions: should nursing take aromatherapy more seriously and do nurses really need 60 hours of massage to use aromatherapy as part of nursing practice? PMID- 17353824 TI - Benefits of interprofessional education in health care. AB - This article examines some of the literature regarding the benefits of interprofessional education (IPE) in the field of health care. These benefits in relation to service users (and carers), higher education institutions, service providers and students are all explored. Barriers to IPE are being broken down by many of the various stakeholders working towards a similar agenda. However, currently there remains some doubt as to whether IPE has a direct positive impact on the health gain of service users and carers. Research is needed to demonstrate if service users and carers benefit directly from IPE and if they do not, the reason for pursuing it needs to be questioned. PMID- 17353825 TI - Modernizing nursing careers report outlines the future. PMID- 17353827 TI - Knowing why patient safety incidents occur in the NHS. PMID- 17353828 TI - Nurses training doctors: evaluation of a fifth year medical school pilot. AB - In October 2004 a request was made to the Royal Centre for Defence Medicine to support a pilot project for a leading Midlands medical school. The aim of the project was to standardize clinical skills training for medical students prior to House Officer jobs. Experienced military emergency nurses provided clinical training including cannulation, catheterization and phlebotomy in a simulated environment. All fifth year medical students attending clinical skills training were invited to complete post-training evaluation questionnaires. The project was evaluated positively and there was an excellent response to nurses training doctors. There was a statistically significant improvement in post-training confidence. All medical students passed their practical assessment following the training programme. This pilot project has been highly successful and has subsequently been extended to all fifth year students at the medical school. The range of clinical skills taught by nurses has also been widened. PMID- 17353829 TI - Using a Delphi approach to develop a strategy for A&E in defence nursing. AB - The Armed Forces has seen an increase in the number of operational deployments overseas and a greater demand for Accident and Emergency (A&E) trained nurses. This article describes a modified Delphi study used to contribute to the development of a strategy for emergency nursing in the Defence Nursing Services. Twenty-eight A&E specialists took part and the key issues raised were recruitment and retention, staff development, new roles, research priorities, increased internal recruitment of A&E nurses to meet operational demands, and the need for a structured career pathway to help retention. The most pressing areas requiring research were evaluation of the nurse practitioner role, clinical competencies and managing heat injuries in the operational setting. The modified Delphi study provided a valuable and detailed insight into the challenges and aspirations of the military A&E nursing cadre and has assisted in developing a strategy for emergency nursing. PMID- 17353830 TI - Keeping experience at the bedside: the emergency consultant nurse role. AB - The consultant nurse concept has not yet been transferred to the military setting. The motivation for developing the role in the NHS was to improve the quality of patient care by strengthening professional leadership and extending the clinical career ladder. The consultant nurse may be defined as an expert in their clinical field, possessing expert leadership and visionary skills. The role is based on four domains: expert practice, professional leadership, education and research. Typically, the emergency consultant nurse spends 50% of their time working clinically, thereby providing senior clinical expertise and adding value to the clinical role. In a military context the consultant nurse role could be perceived as the coming together of the senior command and administrative role and the clinical role. The military has the opportunity to develop a senior clinical emergency nurse role encompassing elements of the civilian consultant nurse model, which may strengthen leadership, provide a central resource of expertise and raise the profile of military nursing. This has the added potential to provide inspiration for junior nurses and retain experienced emergency nurses in the clinical arena. PMID- 17353831 TI - Pathway for patients admitted with gastroenteritis to a military hospital. AB - As part of the Clinical Effectiveness Programme, a care pathway was developed for use within the isolation facility in a military hospital in Iraq. The development of the care pathway was necessary to provide direction and to standardize the care provided. A care pathway using a structured and planned approach was developed, critically appraised and amended to ensure evidence-based and patient focused care. This article provides an amended methodology for the development of further pathways suitable for use within military nursing based on the standard pathway produced by De Lue (2002). The production of the pathway and supporting guideline will ensure standardized care for patients admitted with gastroenteritis. PMID- 17353832 TI - What is the effect of preoperative information on patient satisfaction? AB - The aim of this literature review is to examine the relationship between the provision of written information given to patients' preoperatively and their postoperative recovery following elective surgery. It is not currently apparent which is the most effective method of delivering preoperative information, or at what stage of the preoperative phase is the optimum time to deliver such important information. The purpose of this review is to briefly outline the affiliation between anxiety experienced by surgical patients and the information received preoperatively and to examine the relationship between the provision of written information given to patients preoperatively and their postoperative recovery following elective surgery. Research findings are contradictory with respect to the effect of preoperative information on postoperative pain and patient satisfaction. However, research does indicate that the provision of good quality preoperative information facilitates patients' active involvement in their care, and therefore may contribute to an overall increase in satisfaction. There remains a need for rigorous research that identifies the optimum timing and method of delivering preoperative information to maximize their positive effects on patients undergoing elective surgery. PMID- 17353833 TI - Patients' feelings about hand washing, MRSA status and patient information. AB - The purpose of this study was to explore patient opinion about asking healthcare professionals to wash their hands before a clinical procedure and to explore if methicillin-resistant Staphylococcus aureus (MRSA) status and access to patient information about infection control would influence the patients' anxiety about asking. A descriptive survey was undertaken using a semi-structured questionnaire. The questionnaire was distributed to a randomized convenience sample of 185 inpatients across all departments of an acute NHS Trust hospital (response rate 58.9%). Spearman's rank order and Kendall Tau-b tests were used to analyse specific correlations. Respondents were more confident than anxious about being involved in a campaign that empowered patients to ask staff to wash their hands. Patients were more anxious to ask if their previous admission episodes were fewer, if their knowledge of MRSA was high and if there was less information about infection control available. Patients who had contracted MRSA in the past were less anxious, as they had a better understanding of the disease. In addition, more patients felt less anxious about asking staff to wash their hands if staff wore a badge saying 'It's OK to ask'. PMID- 17353834 TI - Work discussion groups in clinical supervision in mental health nursing. AB - This study aims to explore the value and meaning of a psychodynamic work discussion for mental health nurses, and its potential as an approach in staff clinical supervision. Data were generated by using a focus group with a purposive sample of six mental health nurses, and analysed by the 'collapsing of data' from labels to form categories and formulate themes. The findings suggest that staff emotion generated from clinical work is dealt with in many personal ways though rarely in clinical supervision. Although the idea of a work discussion group is not readily known among the focus group, staff appear to be open to its potential to provide a helpful emotional perspective. Education in the form of an introduction and exposure to some basic psychodynamic ideas could provide the first step towards unlocking its potential. Sharing personal experiences of an emotional nature within a safe, secure environment seems significant in this education process. PMID- 17353835 TI - Nurses' guide to the impact of alcohol on health and wellbeing. AB - In this the second part of this series, the authors map the impact of alcohol on human health and social well-being. While historically nurses have thought of these matters as being distinct, they interact regularly and challenge health professionals in accident and emergency departments, the community and the mental health services. This article discusses how nurses can begin to determine when alcohol consumption has become 'too much'--threatening not only personal health but the well-being of others. The article then examines physical problems that follow alcohol abuse (e.g. brain and liver damage) as well as those associated with social dysfunction (e.g. accidents, aggression and violence). PMID- 17353836 TI - The duty of care 1: compliance with directives and protocols. AB - The first three articles in this series will concentrate on the issue the legal 'duty of care'--the terms of which we as nurses have to understand. The first article examines a recent decision of the High Court of England and Wales that discusses and examines directives and protocols. I have begun with a discussion of the fact that a duty of care not only extends from healthcare providers to patients (clients) but also from employers to employees, and between healthcare providers themselves. PMID- 17353837 TI - Developing the role of a ward housekeeper within a multidisciplinary team. AB - The implementation of a housekeeper induction competency programme demonstrates the innovative way that the clinical standards facilitator has led the development of the housekeeping service at one NHS Trust. This service has been developed to ensure that there is sufficient training, support and opportunity to share best practice for the housekeepers. A Trust-wide approach using the multidisciplinary team (including dieticians, catering and facilities managers) has contributed to the raising of standards in meeting the patients' nutritional needs, as well as improving the ward environment. NHS Estates guidance (DH, 2001b) relating to the housekeeping service and the Essence of Care benchmarks for nutrition (DH, 2001a) were used to provide this framework for continuous quality improvement. PMID- 17353838 TI - Review 2006. NHS key issues: finance, care, continuity. PMID- 17353839 TI - Avoiding complacency in palliative care. PMID- 17353840 TI - Compassion in the workplace? Discrimination against an employee with cancer. AB - Rachel is a designer based in the UK. In the following account, she describes the experiences of her colleague Jack, designer and studio manager, during his battles with colon cancer and with his employers. The article raises the issues of difficulties faced in the workplace by patients with cancer and other life threatening illnesses. PMID- 17353841 TI - A practical guide for nurses in diluent selection for subcutaneous infusion using a syringe driver. AB - Appropriate diluent selection in continuous subcutaneous infusion optimises symptom management and client well-being. The responsibility of diluent selection is commonly one of the attending nurse. This paper was developed with the intention of providing nurses with practical instruction for diluent selection when preparing medications for administration subcutaneously using a syringe driver. A literature review was undertaken of published journal databases and published guidelines sites. Recommendations regarding diluent choice were reviewed in two iterations by an expert panel of palliative care nurse clinicians. The principles for diluent selection are presented. They are based primarily on expert opinion level of evidence given a lack of primary research evidence in the area of diluent selection. There is a pressing need for manufacturers' guidance on diluent selection and independent research to establish the impact of diluents on drug and drug combinations when using syringe drivers. Until such time that this evidence is available to guide practice, clinicians need to be trained to inspect solutions and assess the effectiveness of the medication in controlling symptoms. The capacity of this paper to provide practical instruction has been limited by the lack of rigorous evidence available, and indeed, the process of developing this guide identified perhaps more questions than answers available at the present time. PMID- 17353842 TI - Managing beyond an uncertain illness trajectory: palliative care in advanced heart failure. AB - A lack of comprehensive and effective palliative care is clearly evident in a number of studies describing the end of life for patients with advanced heart failure. These patients have been portrayed as experiencing a wide array of poorly managed symptoms. The primary rationale for the lack of care has been the uncertain illness trajectory that characterizes living with advanced heart failure. Nurses must manage care beyond the illness trajectory from an emphasis of palliative care as each of these patients may face significant illness burden and even sudden death. The purpose of this paper is to: discuss the current status of palliative care for patients with advanced heart failure; explain the basic pathophysiology and resulting signs and symptoms of advanced heart failure; describe pharmacological and non-pharmacological symptom management strategies for patients with advanced heart failure. PMID- 17353843 TI - Impact on parents when a child has a progressive, life-threatening illness. AB - Children with neurodegenerative, life-threatening illnesses (NLTIs) account for a significant proportion of children requiring palliative care, yet there is a lack of of research that examines families' experiences. This grounded theory study generated a contextually-grounded description of the experiences of families living with a child who has an NLTI. Data were collected from eight families (n=29 family members) through observations and audiotaped interviews. The impact on parents was pervasive and multidimensional. Parents faced many emotional, physical, financial, and spiritual impacts on their lives. Parents often needed help to alleviate the impact of their experience, but it was not always available in a useful manner. Despite the negative aspects, caring for the child was never viewed by parents as a burden. Fatigue was a particularly prevalent symptom that held the potential to impact on parents in multiple ways. Suggestions for practice and research are offered to assist health care professionals in providing optimal pediatric palliative care to these families. PMID- 17353844 TI - Nurses and palliation in the community: the current discourse. AB - A core component of community nursing practice in Australia is the provision of palliative care, however this area of practice has been minimally researched. We, therefore, undertook a broader review of the contemporary literature in community nursing; palliative nursing; and community nursing palliative care. Literature was searched electronically in OVID, CINAHL and nursing databases and manually in relevant journals. Findings revealed community and palliative care nursing to be both complex and challenging. Community and palliative nurses ideals for care are compromised by competing practice demands. Changing health systems and philosophical views, limited resources and the perceived 'visibility/invisibility' polarity are identified as major job stressors. Therapeutic use of 'self' and interpersonal communication are recognized as contributing to job satisfaction. Community nurses providing palliative care is as an under researched area yet it is a role that arguably requires critical understanding and recognition. Further research is needed into the relationship between emotional well-being and professional satisfaction for community and palliative care nurses providing palliation. PMID- 17353846 TI - Constipation and palliative care - where are we now? AB - Constipation is an unpleasant and distressing symptom that many palliative care patients may experience, often having a profound effect on their quality of life. The many management options available reflect the multifactorial nature of constipation. The article explores the complexity of constipation in palliative care and highlights the challenge of managing opioid-induced constipation. Advances in the pharmacological and non-pharmacological management of constipation are reviewed and discussed in the light of relevant research. Further discussion includes definitions, incidence and causes of constipation in palliative care. PMID- 17353847 TI - The pain of residents with terminal cancer in USA nursing homes: family members' perspectives. AB - Cancer pain continues to be poorly treated despite efforts aimed at improvement. This causes considerable distress to both patients and their families. The purpose of this research is to explore the perspectives of family members of nursing home residents with terminal cancer, about pain and pain management. Participants who believed their pain could be better managed viewed their family member's pain and illness differently than those who believed the pain could not be managed better. The family members who believed better pain management was possible often took on the role of advocate and saw to it that the pain was addressed. Those who believed that their relative did not have adequate pain relief, but felt better management was not possible, expressed no concerns about this aspect of their relatives' care; they could not separate their relatives' pain from their illness. The interpretation and presence of adequate pain management is critical for family members to construct meaning around their relative's pain. When family members do not believe that the pain can be managed any better, this acts as a barrier to the resident's access to adequate pain management. PMID- 17353848 TI - Racial differences in perceptions held by caregivers of long-term ventilator patients at end of life. AB - AIM: The purpose of this pilot study was to describe and compare perceptions of preparation for death and satisfaction with end-of-life care in African American and Caucasian caregivers of long-term ventilator (LTV) patients. DESIGN: A comparative descriptive design was used to pilot test items from specific domains from the After-Death Bereaved Family Member Interview. Interviews were conducted on 37 bereaved caregivers of LTV patients who participated in a large experimental study. FINDINGS: There was a statistically significant association between African American and Caucasian caregivers in the area of being informed of the patient's condition. African American caregivers felt more informed than Caucasian caregivers. Over half of African American and Caucasian caregivers reported feeling 'fairly to very confident' about what to expect when their loved one was dying. CONCLUSION: Health care providers should be sensitive to potential differences between African American and Caucasian family caregivers in providing end-of-life care. PMID- 17353849 TI - Factors influencing completion of advanced directives in hospitalized patients. AB - AIM: A cross-sectional, descriptive study to describe characteristics and other factors that influenced the decision by hospitalized patients in the East Texas area to formulate an advanced directive (AD). FINDINGS: Spouses, family members and sense of spirituality were the strongest influential factors for completion of an AD. Most learned about ADs from family, friends, personal attorneys, and others, while less than a quarter of the sample learned about ADs from health care providers. Not wanting to be a burden on their family was the major reason cited for completing an AD. CONCLUSIONS: Health care provider roles are vague in terms of responsibility for AD discussion and education. Further exploration of the attitudes, knowledge and practices concerning ADs of nurses and primary health care providers is recommended to provide focal points for future research in order to facilitate peace of mind for patients and families at end-of-life. PMID- 17353850 TI - Laparoscopic approach to morbid obesity: personal experience of 250 gastric bypasses. Analysis of different techniques and results. AB - AIM: Severe obesity is a major health problem affecting more than 1,000,000 people in Italy, with a 95% failure rate of nonsurgical treatments. We report our over five-years experience with laparoscopic Roux-en-Y gastric bypass (LRYGBP), evaluating the postoperative course of the patients undergoing 3 different gastro esophageal anastomosis technique: Gagner procedure (87 cases) (34.8%), the purse string approach (93 cases) (37.2%), robotic-assisted gastric bypass (68 cases) (27.2%) and by laparoscopic hand sewn anastomosis (2 cases) (0.8%). METHODS: Between October 2000 and February 2006, we performed LRYGBP on 250 patients (77 male and 173 female aged from 16 to 65 years [mean age 43.1 years] and with an average body mass index of 51.1 kg/m(2) [35-99]). Comorbidities were: hypertension, type II diabetes, hyperlipemia, osteoarthritis, chronic restrictive pulmonary insufficiency, sleep apnea, deep venous thrombosis. RESULTS: The mean operative time was 142.3 min (80-420) with a mean hospitalization of 9.8 days (5 44). Eighteen major complications were recorded. There were no deaths. The mean percent excess body weight loss was 47.2+/-18.2% after 1 year (212 patients), 66.2+/- 19.4% after 2 years (178 patients), 78.2+/-12.4% after 3 years (139 patients), 80.6+/-11.7% after 4 years (101 patients), and 82.5+/-10.2% after 5 years (67 patients). Nearly all of the comorbidities were solved or improved. Bariatric analysis and reporting outcome system results after 5 years were excellent, good or fair in 100% of the subject evaluated. CONCLUSIONS: Although requiring the skill of an expert surgeon, LRYGBP is one of the most effective procedure available today to induce long-term weight loss, with limited nutritional risks and better prospects for improved quality of life. PMID- 17353851 TI - Sentinel lymph node biopsy in the treatment of breast cancer. Experience in 527 cases. AB - AIM: Knowledge of axillary lymph node status is a key aid to staging and prognosis and it represents a guideline for adjuvant therapy in breast cancer. Despite the morbidity it causes, complete axillary dissection was long the mainstay of treatment. Sentinel lymph node biopsy has proved so reliable in the evaluation of node involvement that axillary node dissection is now generally performed when sentinel node biopsy tests negative. METHODS: In this 3-phase study, 50 patients were enrolled to evaluate the learning curve of sentinel node biopsy (phase 1, September 1997-January 1998); 256 patients (age range 27-81 years) with infiltrative breast cancer (T <3 cm, clinical N0) underwent level 1 lymph node dissection when the sentinel node tested negative at histopathology (phase 2, February 1998-March 2001); 221 patients with T <3 cm underwent dissection of the sentinel node when it tested negative for metastasis (phase 3, April 2001-March 2005). RESULTS: The sentinel node was preoperatively detected in 98.6% of cases after peritumoral and intradermic injection of the radionuclide tracer and intraoperatively in 99% (90% with radio-guided surgery, 10% with vital staining). The sentinel node was positive in 15% of patients with T1 and metastatic in 65%. CONCLUSIONS: Our results are in line with the published data; therefore, the study will go forward to examine the role of the micrometastasis in the sentinel node and of in-transit tumoral cells. PMID- 17353852 TI - [Short-term results in colorectal surgery. Statistical analysis about mortality, morbidity and hospital stay]. AB - AIM: The surgical approach on the colon and rectum represents a wide slice of the surgical procedures carry out in election or emergency in a general surgery unit. The literature reports prospective and retrospective studies evidencing emergency surgery, advanced age, comorbidity and other factors can determinate a worsening of short-term outcome (postoperative mortality, morbidity and hospital stay). The aim of the study was to verify, through a statistical analysis on a group of patients operated on the colon and the rectum, which are the factors weighting on the short-term outcome. METHODS: Our retrospective study is carried out on 150 patients consecutively operated on the colon and rectum from January 2002 to September 2004 in elective or emergency surgery in the Unity of General Surgery of the Hospital S. Maria Nuova Azienda Sanitaria of Florence. The variables for the statistical analysis were: sex, age, comorbidity, nature of pathology, timing of surgery, type of emergency, lesion location, surgical intervention, presence of social factors delaying the discharge, blood transfusion, Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM score). RESULTS: The mortality study found the advanced age (>70 years) as risk factor in the univariate analysis, not confirmed in the multivariate one. The morbidity study found advanced age, presence of comorbidity and blood transfusion as risk factors in the univariate analysis, not confirmed in the multivariate one. The POSSUM-score represents in both multivariate analyses the only statistically meaningful parameter correlated with mortality (P<0.005) and morbidity (P<0.05). The multivariate analysis in the study on the hospital stay found that more staged surgery carry to a lengthening of hospital stay (P<0.0001); in minor such measure blood transfusion (P=0.0005), emergency surgery (P=0.002) and presence of social factors (P=0.008); comorbidity (P=0.02) and advanced age (P=0.03) had less statistical weight. CONCLUSIONS: Despite of the literature, this study found none of the analyzed variables related on postoperative mortality and morbidity in statistically meaningful way. The POSSUM score demonstrated once again validity in estimating the probability of dead and of postoperative complications. The variables that influenced in lengthening of hospital stay were: more staged surgery, blood transfusion, emergency surgery, presence of social factors conditioning the discharge, comorbidity and advanced age of the patients. The good results about mortality and morbidity can be explained by the fact we prefer in emergency more staged surgery that protect the patients from complications related to the anastomosis, the presence of sub intensive surgical beds with a constant monitoring of high risk patients and the close collaboration between surgeons and intensive care medical doctors. PMID- 17353853 TI - Pedal bypass grafting on arteriographically invisible foot arteries detected by duplex ultrasound for limb salvage. AB - AIM: In this study the long-term outcomes in patients undergoing pedal bypass grafting were evaluated and the risk of graft occlusion was related to whether, preoperatively, the pedal arteries were visualized by angiography or not and were only detected by duplex ultrasonography. METHODS: In 2000-2005, 81 pedal bypass grafts were performed in patients with chronic critical lower-limb ischemia, of which 54 (66.7%) had diabetes. Tissue loss (SVS/ISCVS-category 5) was recorded in 68 (84%) limbs and rest pain (SVS/ISCVS-category 4) in 13 (16%) limbs. In 24 limbs (29.6%) bypass grafts were implanted on the pedal arteries that had not been visualized by preoperative angiography, but had been detected only by duplex ultrasound. RESULTS: During the follow-up (median, 17 months; range, 3-69 months), 18 grafts (22.2%) failed. Seven limbs had to be treated by early thrombectomy, which resulted in long-term graft patency and limb salvage. The early postoperative mortality rate was 2.5%. Cumulative primary and secondary graft patency rates, and limb-salvage rates were 70.2%, 80.2% and 82.4%, respectively. No significant difference in graft occlusion was found between the patients with visible and those with not visible pedal arteries on preoperative arteriograms (Fisher's exact test). CONCLUSIONS: Duplex ultrasonography is a reliable modality for detection of target pedal arteries not visualized by preoperative arteriography and it helps reduce the number of patients with non operable arterial occlusion disease by about 25%. PMID- 17353854 TI - [Subfascial endoscopic perforating vein surgery in patients with advanced trophic lesions (lipodermatosclerosis or ulcers)]. AB - AIM: Subfascial endoscopic perforating vein surgery (SEPS) is proposed in the treatment of chronic venous insufficiency stages C4-C6 of the CEAP classification. METHODS: SEPS was performed in 10 patients (4 men, 6 women), 3 of which were stage C4, 4 stage C5 and 3 stage C6. RESULTS: Full resolution of ulcers was achieved in the 12-month follow-up period; no post-operative sepsis complications were observed. CONCLUSIONS: SEPS is a safe procedure and a valuable therapeutic aid in the treatment of chronic venous insufficiency complicated by trophic skin ulcers. Compared with other techniques, it is less invasive, works directly on the healthy skin and significantly reduces skin wounds. PMID- 17353855 TI - Mirror image Berry syndrome: a case report of complex aortopulmonary malformation in viscero-atrial situs inversus. AB - We report a very rare case of an infant with viscero-atrial situs inversus presenting mirror image Berry syndrome (aortopulmonary window, interrupted aortic arch, anomalous origin of the left pulmonary artery, and intact ventricular septum). Successful surgical treatment was accomplished 56 days following the initial rescue bilateral pulmonary artery banding. PMID- 17353856 TI - Pericardial cyst located in the anterior mediastinum mimicking a thymoma. A presentation of two cases. AB - Pericardial cysts are rare but well recognized tumors of the mediastinum. Most pericardial cysts are located in the right or left cardiophrenic angle. At other locations these cysts may pose a diagnostic problem. We present two cases of an atypically located pericardial cyst and a short review of the literature. PMID- 17353857 TI - A safe and effective method for an immediate bronchopleural fistula repair. AB - Bronchopleural fistula (BPF) is a well recognized and potentially fatal complication of major thoracic surgery and several strategies regarding its prevention and subsequent management have been described. An immediate BPF occurring intraoperatively after bronchial closure is a rare event and is usually treated by bronchial stump reamputation and/or hand-suture reinforcement by mattress suture, or myoplasty. We report a simple and successful technique, using azygous vein flaps, to repair an intraoperative BPF associated to a small bronchial dehiscence occurred after a right pneumonectomy in a 70-year-old diabetic man receiving induction chemotherapy treatment. PMID- 17353858 TI - [Cholecysto-gastric fistulas: case report and literature revision]. AB - Authors report a recent case of cholecysto-gastric fistula. On the basis of their own experience and of the literature, authors discuss the pathogenesis of the cholecysto-enteric fistulas and underline the relative non frequent of fistulas with the stomach. Authors stress the available diagnostic and therapeutic features and believe that this disease deserves, whenever possible, a surgical correction. PMID- 17353859 TI - Laparoscopic excision of a retroperitoneal cystic lymphangioma in an elderly patient. AB - A 68-year-old male patient was referred to our hospital due to protrusion and pain in the right iliac fossa. On physical examination a palpable oval tumor was found. Ultrasonography and computed tomography revealed a cystic mass in right iliac fossa. The tumor was successfully excised laparoscopically and histologically diagnosed as cystic lymphangioma. Retroperitoneal cystic lymphangiomas are rare lesions, most often seen in pediatric patients. Surgical excision is the treatment of choice because of its potential to grow and develop complications, especially due to mass effect. The laparoscopic approach is a safe and effective alternative for treatment of retroperitoneal cystic lymphangioma in the elderly. PMID- 17353860 TI - Macroscopic appearance of the bowel predicts microscopic involvement in gastrointestinal Wegener's granulomatosis: a previously unreported sign. PMID- 17353861 TI - [(111)In]Pentetreotide SPECT scintigraphy in neuroendocrine tumors: variability of reconstructing parameters related to patient characteristics and each body part. AB - AIM: Multi-headvariable-geometry gammacamera, allow us to carry out multi dimensional scintigraphic single photon emission computed tomography (SPECT) studies, with the possibility of creating coronal, axial, sagittal, three dimensional images like the last generation of multi-slice RMI or multislice CT scan. The aim of this paper is to weigh up the reconstruction parameters to apply in [(0111)In]Pentetreotide scintigraphy for evaluating neuroendocrine tumors and try to standardize them. METHODS: We have studied a group of 93 patients suffering from neuroendocrine tumors. Examination was carried out after administration of [111In] Pentetreotide with whole body and static acquisitions after 4 and 24 h, followed by SPECT acquisitions of head, thorax and abdomen after 24 h. RESULTS: The results obtained show that the Filtered Back Projection using Butterworth filter can produce images of greater resolution than the iterative reconstruction method. Moreover, the reconstruction parameters are easily standardizable for head and thorax while for the abdomen the choice of these parameters is more difficult. CONCLUSIONS: Our data show that filtered back projection with Butterworth filter is the best procedure to carry out a SPECT examination with [111In] Pentetreotide. PMID- 17353862 TI - Accurate planning of minimally invasive surgery of parathyroid adenomas by means of [(99m)Tc]MIBI SPECT. AB - AIM: The aim of the study was to evaluate the clinical role or [(99m)Tc]MIBI SPECT in selecting primary hyperparathyroid (PHPT) patients for minimally invasive radioguided surgery (MIRS). METHODS: One hundred and forty-one consecutive PHPT patients were studied by a single-session [(99m)Tc]Percethnetate/[(99m)Tc]MIBI subtraction scintigraphy, followed by [(99m)Tc]MIBI SPECT in order to localize hyperfunctioning parathyroid adenoma (PA) and plan the surgical approach. RESULTS: A solitary PA was depicted at preoperative scintigraphy in 135 of 141 patients (95.7%), two or more PA in 5 patients, and was negative in 6 patients (4.3%). In 27 patients, the PA was located deep in the paraesophageal/paratracheal space. One hundred and twenty four patients (in 18 of them the PA was located deeply in the neck) underwent successful MIRS using the low 37 MBq (1 mCi) [(99m)Tc]MIBI dose protocol. Intraoperative quick parathyroid hormone (QPTH) assay demonstrated a fall >50% in respect to the baseline value in all patients, confirming successful parathyroidectomy. After a follow-up of 6 to 37 months (median 18 months), no case of persistent/recurrent PHPT was recorded. When comparing the parathyroid to background (P/B) ratio measured at planar and SPECT preoperative scintigraphy with that measured intraoperatively with the gamma probe, a significant linear correlation was found between the SPECT and intraoperative gamma probe measurements (r = 0.91; P <0.01) while no correlation was found with planar scintigraphic data. CONCLUSIONS: Our data suggest that the P/B ratio calculated by means of [(99m)Tc]MIBI SPECT is more accurate in predicting the intraoperative measurements with the intraoperative gamma probe. Thus, a preoperative [(99m)Tc]MIBI SPECT acquisition should be recommended for a better selection of PHPT patients to offer MIRS. PMID- 17353863 TI - Erectile vascular dysfunction and analysis of the risk factors related to it: clinical experience. AB - AIM: Preliminarily we analyzed the rate incidence of organic and psychological causes of erectile dysfunction in large cohort of patients observed during last year. Particularly we wanted to analyze the factors of risk correlated to the vascular erectile dysfunction. METHODS: The epidemiological study has been conducted on a cohort of 101 patients (age 25-75 years) suffering from erectile dysfunction since 1-10 years (average: 2.6 years) and administrated during the last year by the Institute of Andrology at the University of Catania. RESULTS: The organic erectile dysfunction had a frequency more elevated in comparison to the psychological erectile dysfunction, respectively engraving in 54.5% and in 45.5%. Between the organic causes of erectile dysfunction, the vascular arterial forms of erectile dysfunction represented highest rates (32.7% of the patients). The group of patients affected by vascular arterial erectile dysfunction showed several factors of risk, present in all the patients in single or combined way (comorbidity). The rate of such factors was >30% for 4 examined factors: hypertension (57.5%), smoke (45.4%), diabetes mellitus (39.3%), hyperlipidaemia (33.3%). CONCLUSIONS: The erectile dysfunction is frequently associated to organic causes, prevalently of arterial vascular nature. The correction of the factors of risk could lead to a better control of the erectile dysfunction and reduce the extension of the vascular arterial damage to other districts. PMID- 17353864 TI - Gender difference: fertility preservation in young women but not in men exposed to gonadotoxic chemotherapy. AB - Decreased secretion of pituitary gonadotropins, by decreasing gonadal function, may possibly protect against the sterilizing effects of chemotherapy. Although previous claims that primordial germ cells fare better than germ cells that are part of an active cell cycle have been made, this hypothesis has not been seriously tested clinically until recently. The only prospective randomized study performed to date found that gonadotropin releasing hormone agonistic analogue (GnRH-a) protected the ovary against cyclophosphamide-induced damage in Rhesus monkeys by significantly decreasing the number of follicles lost during the chemotherapeutic insult. We have administered a monthly depot i.m. injection of GnRH-a to more than 125 young patients exposed to gonadotoxic chemotherapy for malignant or nonmalignant diseases, after informed consent, starting before chemotherapy for up to 6 months, in parallel and until the end of chemotherapeutic treatment. Less than 7% developed irreversible hypergonadotropic amenorrhea. The remainder (>93%) resumed cyclic ovarian function, of which 32 patients spontaneously conceived 46 times. These patients were compared to a control group of over 125 patients of comparable age (15-40 years), who were similarly treated with chemotherapy but without the GnRH-a adjuvant. The 2 groups were similar in age, diagnosis, and the ratio of HD to non-Hodgkin lymphoma patients. The 2 groups also received similar doses of radiotherapy exposure and the proportion of radio-plus chemotherapy-treated patients was similar. The cumulative doses of each chemotherapeutic agent and the mean or median radiotherapy exposure did not differ between the groups. Our and others' results support the effectiveness of GnRH-a administration also to patients receiving cyclophosphamide pulses for systemic lupus erythematosus and other autoimmune diseases. Possible explanations for the beneficial effect of the GnRH-a on minimizing the gonadotoxic effect of chemotherapy are discussed. Multi-center prospective, randomized studies are awaited to substantiate the in vivo effect of GnRH-a as an unequivocal means of minimizing follicular apoptosis. PMID- 17353865 TI - Polycystic ovarian syndrome: the commonest cause of hyperandrogenemia in women as a risk factor for metabolic syndrome. AB - Polycystic ovarian syndrome (PCOS), the commonest endocrine disorder of women, is currently emerging as a potential facet of the metabolic syndrome (MBS) in women. Available data suggest that the MBS or, alternatively, individual metabolic risk factors may be overly present and most importantly that MBS may arise at a significantly younger age among PCOS women. The concept that a conventionally considered reproductive disorder may entail a significant metabolic impact on affected women has warranted medical interest on the mechanisms underlying the multiplicative sequelae of PCOS. Although obesity indisputably compounds the clinical course of women with PCOS, this appears to be just the tip of the iceberg. Insulin resistance and hyperinsulinemia have been intuitively involved as a critical link due to their contribution to the pathophysiology and clinical presentation of both PCOS and MBS. Hyperandrogenemia, the predominant endocrine hallmark of PCOS, has also been implicated as a contributing factor to the suggested interrelationship. PMID- 17353866 TI - Neuropsychiatric aspects of hypothyroidism and treatment reversibility. . AB - Thyroid hormone has important actions in the adult brain, and it is well accepted that hypothyroidism is associated with neuropsychiatric complaints and symptoms. Neuropsychiatric symptoms refer to a spectrum of emotional and cognitive problems that are directly related to changes in the brain secondary to multiple factors, including the direct effects of thyroid disease, as well as hormone deprivation in brain tissue. Hypothyroidism impacts aspects of cognitive functioning and mood. More severe hypothyroidism can mimic melancholic de-pression and dementia. Neuropsychiatric symptoms tend to improve with treatment and normalization to a euthyroid state, though the pattern is inconsistent and complete recovery is uncertain. The degree to which mild hypothyroidism, or subclinical hypothyroidism (SCH), impacts mood and cognitive functions and whether these symptoms respond to treatment, remains controversial. Most studies support a relationship between thyroid state and cognition, particularly slowed information processing speed, reduced efficiency in executive functions, and poor learning. Furthermore, hypo thyroidism is associated with an increased susceptibility to depression and reductions in health-related quality of life. Controlled studies suggest that cognitive and mood symptoms improve with treatment, though the data are equivocal and limited by diverse methodologies. Functional neuroimaging data provide support for the mood and cognitive findings and treatment reversibility for both overt and SCH. These findings are not, however, without controversy. Recent investigations into the impact of SCH on cognition and mood, coupled epidemiological studies investigating the normal spectrum of thyroid stimulating hormone, have fueled significant debate regarding the appropriate, healthy range for TSH levels. This has led to concern over whether patients with overt hypothyroidism may be undertreated and whether SCH patients are truly out of the range of normal thyroid functioning and should be treated. The following is a review of the extant literature on the impact of hypothyroidism on cognition and mood, reversibility of symptoms, and treatment approaches. The spectrum of thyroid disease is reviewed, but mild, or subclinical, hypothyroidism is emphasized. The potential role of autoimmunity in neuropsychiatric symptoms and treatment resistance is addressed. Limitations of the current literature and future directions are discussed. PMID- 17353867 TI - Androgen excess and cardiovascular risk. AB - Cardiovascular diseases represent the major cause of death in most of developed countries and ultimately kill as many men as women. Both genders are exposed to the same risk factors but their rates of cardiovascular morbidity and mortality are very different until old age. This represents a crucial point; in fact, only at age 75 and over cardiovascular rates of women approximate those of men. It has been suggested that differences in hormonal status and mainly in androgen levels may explain such gender disparity. Consistently with this hypothesis, it has been shown that women with polycystic ovary syndrome (PCOS) have elevated cardiovascular risk despite their young age. However, the possibility that androgens may increase cardiovascular risk remains controversial. Hyperandrogenism, as isolated androgen excess, has not been clearly recognised so far as a risk factor for cardiovascular diseases. In addition, the risk of premature cardiovascular diseases in PCOS is at present uncertain. Long-term studies examining the prevalence of cardiovascular diseases among women with PCOS did not demonstrate a clear increased risk for cardiovascular morbidity and mortality. Thus, it seems that androgens have a limited role in inducing cardiovascular risk; the altered risk factors found in women with PCOS are mainly dependent on the metabolic components of this syndrome as well as on insulin resistance and reduced adiponectin secretion. PMID- 17353868 TI - [Laparoscopic supracervical hysterectomy versus laparoscopic total hysterectomy: a prospective randomized study]. AB - AIM: The aim of this study was to compare surgical complications and clinical outcomes after supracervical versus total laparoscopic hysterectomy for the control of abnormal uterine bleeding or symptomatic uterine leiomyomata. METHODS: We conducted a prospective randomized trial on 141 patients who had laparoscopic hysterectomy for symptomatic uterine leiomyomata, abnormal bleeding refractory to hormonal treatment, or both. Patients were randomly assigned to receive a supracervical or total laparoscopic hysterectomy. We compared surgical complications and clinical outcomes for 2 years after randomization. RESULTS: Seventy-one participants were assigned to supracervical laparoscopic hysterectomy (SLH) and 70 to total laparoscopic hysterectomy (TLH). Hysterectomy by either techniques led to statistically significant reductions in most symptoms, including pelvic pain or pressure, back pain and urinary incontinence. Patients assigned to SLH tended to have more hospital readmissions than those randomized to TLH. There were no statistically significant differences in the rate of complications, degree of symptoms improvement, or activity limitation. Participants weighing more than 100 kg at study entry were more than twice as likely to be readmitted to the hospital during the 2-year of follow-up (OR 2.48, 95% CI 0.11; 1.91, P=0.04). CONCLUSIONS: We did not observe statistically significant differences between SLH and TLH in surgical complications and clinical outcomes during the 2-years of follow-up. PMID- 17353869 TI - Evaluation of clinical efficacy of three different insemination techniques in couple infertility. A randomized study. AB - AIM: The aim of the study was to compare the clinical results and efficiency of three insemination technique: intraperitoneal insemination (IPI), fallopian sperm perfusion (FSP) and intrauterine insemination (IUI). METHODS: The experimental design was a prospective, randomized trial. A total of 101 homologous insemination cycles were performed in 71 consecutive couples with unexplained or male subfertility. Couples were randomized to receive IPI or FSP or IUI by predefined tables of randomization and each couple was submitted to the same insemination technique. The primary outcome of the study was the achievement of clinical pregnancy. RESULTS: The results of the study underlined firstly that basal couple composition was not statistically different between the three groups. Moreover, no significant difference in clinical pregnancy rate was observed, despite a clearly positive trend for FSP, especially for unexplained infertility. CONCLUSIONS: Our results showed that the three techniques of insemination IUI, FSP and IPI have similar efficacy on the achievement of clinical pregnancy in couples affected by longstanding infertility. PMID- 17353870 TI - The laparoscopic treatment of bladder endometriosis. A retrospective analysis of 21 cases. AB - AIM: Endometriosis is the presence of endometrial tissue, including endometrial glands and stroma, outside the uterine cavity. The incidence of endometriosis in the general population is almost unknown, because it varies between 1% and 50%, depending on the paper considered. In any case, the incidence of bladder endometriosis is generally considered about 1% or less of endometriotic patients. The aim of this study is to evaluate the effectiveness of preoperative exams and the effectiveness of laparoscopic treatment. METHODS: We enrolled 21 patients operated laparoscopically for a severe stage of endometriosis, including at least a bladder localization of 10 mL; in 60% of cases a bowel surgery was associated in the cause of a digestive endometriosis. A complete preoperative and follow-up evaluation was carried out for all patients. RESULTS: The preoperative investigation, especially abdominal sonography, predicted endometriotic bladder invasion in only 38% of cases. Urinary symptomatology was present in only 61.9% of cases. The postoperative follow-up showed the remarkable effectiveness of laparoscopic treatment for the cancellation of pain and to improve the quality of life for patients. CONCLUSIONS: Finally, the treatment of severe endometriosis is possible and effective by laparoscopy even in the cases where there is a bladder localization and when, in the absence of specific symptomatology, it isn't diagnosed preoperatively. PMID- 17353871 TI - [Fertility after surgery for rAFS stage III and IV endometriosis]. AB - AIM: The aim of this paper was to assess the impact on fertility of surgery to eradicate endometriosis. METHODS: One-hundred and twenty-six patients aged between 20 and 40 were observed. All wished to have offspring after the operation and were subjected to conservative surgery for stage III and IV endometriosis (rAFS score > 16) in the period 1992-2002. The type of surgical approach was chosen in consideration of the patient's clinical condition and on the basis of the experience of the surgeon, with the aim of radically removing the disease and, where necessary, restoring fertility. RESULTS: Fifty-six of 126 patients (44.4%) conceived after the operation; 55 spontaneously and 1 with assisted fecundation. Of the patients observed who became pregnant, about 1/3 (32%) conceived within 6 months of the operation and 1/3 (31%) after 12 months. Forty four (78.5%) pregnancies reached term with a positive outcome, 7 (12.5%) were in progress at the moment of follow-up, 4 (7.1%) suffered a miscarriage and 1 (1.7%) was extrauterine; 48.2% (27/56 patients) of the pregnancies were stage III, 40% (28/70 patients) were stage IV. CONCLUSIONS: It emerges clearly from the data extrapolated from our series that surgery to eradicate endometriosis increases the fertility of the patients affected, without being resolutive: more than half the patients in fact remained sterile in spite of the operation. PMID- 17353872 TI - [Ageing and male sexuality]. AB - Visceral, hormonal and neuroendocrine changes after the sixth decade of life result from slowing down and alteration in metabolic, hormonal, protein, lipid and glucose turnover, progressive receptor insensitivity, degenerative processes- primarily arteriosclerosis--of the endocrine and non endocrine tissues. Unlike menopause, andropause has no biological speed; it is neither rapid nor marked by macroscopically evident psychobehavioral change, as occurs in women. Because of its indistinct and widely variable nosographic contours, the male climacterium is more complex. The challenge to the clinical sexologist, therefore, is to identify appropriate treatment approaches for an ageing population with an increasingly longer life expectancy and the right to a sexually satisfying life. PMID- 17353873 TI - Androgen deficiency in older men. AB - Androgen deficiency in older men can be related to age associated changes of neuro-endocrine mechanisms controlling the hormones secreted by the testis and adrenal cortex. We listed the clinical consequences of androgen deficiency at three different levels in three areas: somatic (body composition, glucidic and lipid metabolism, erythropoiesis), sexual and psychological (cognition and affectivity). Observational studies and randomized placebo controlled trials have been reviewed from medical literature. Testosterone, now preferentially administered as transdermal gel, and dehydroepiandrosterone represent two possible treatments. New compounds designed to target androgen receptors in specific tissues are promising options as anabolic agents. PMID- 17353874 TI - Clinical diagnostic approach to erectile dysfunction. AB - Erectile dysfunction (ED) has been defined by the National Institutes of Health (NIH) as the inability to achieve and/or maintain an erection for a satisfactory sexual intercourse. Data on ED epidemiology estimate a prevalence of 12-52%; the prevalence in Italy is 12.8%. ED is a symptom, sometimes the first, of numerous internal diseases. ED can mark the point where the evaluation and prevention of illnesses (diabetes, arterial hypertension, atherosclerosis) hitherto unknown by the patient can begin. The andrologist's task is to identify the disorder underlying ED and to plan the appropriate diagnostic work-up. PMID- 17353875 TI - [Polycystic ovary syndrome and obesity: non pharmacological approaches]. AB - In patients affected of polycystic ovary syndrome (PCOS), obesity has an high percent of incidence and represents an important factor increasing its clinic evolution, both in metabolic than in reproductive terms. For these patients non pharmacologic treatments aimed at the reduction of body weight, such as diets and physical exercise, represent the first line therapeutic approach. The aim of this review is to analyze the changes in life style and to highlight their efficacy in reducing the negative effects of PCOS on metabolism and reproductivity. Specifically different types of diet have been compared, in health or PCOS women, such as low glycemic index diets, moderate carbohydrate, high protein and low fat diets, very low carbohydrate and high fat diets and, finally, moderate carbohydrate and high monounsaturated fat diets. In the global view of the approach to the disease, different regimens of physical activity and the usefulness of a behavior therapy were also evaluated. Results obtained in health women suggest that diets higher in proteins and lower in carbohydrates are to be preferred to the conventional diet lower in fats and higher in carbohydrates. Anyway other studies are necessary to justify a similar assertion in women with PCOS. At the same way, the optimum regimen of physical exercise for PCOS women is still to be demonstrated. PMID- 17353876 TI - [Prenatal medicine: from the obstetric stethoscope to the computerized telecardiotocography]. AB - The aim of this article is to illustrate the history of fetal auscultation from the 19(th) century, when the fetus was considered as an object and the obstetrician as a ''mechanic of the birth'', to the present age, when the fetus is a subject and the obstetricians have at their disposal all the means they need to confirm his well-being and to early diagnose his pathologies, even using prenatal telemedicine. PMID- 17353877 TI - Hydrothorax following ovarian hyperstimulation for assisted reproduction. Case report and review of the literature. AB - In case of ovarian hyperstimulation syndrome, the high incidence of dyspnea in relation with ascites and enlarged ovaries should not justify omission of thoracic evaluation. This manuscript reviews the pathogenesis and clinical presentation of hydrothorax following controlled ovarian hyperstimulation. In addition, we describe the case of a 33-year-old woman with a right massive hydrothorax resulting from controlled ovarian hyperstimulation for intracytoplasmic sperm injection. PMID- 17353878 TI - Ultrasound findings of a rare congenital skeletal dysplasia: Stuve-Wiedemann syndrome. AB - Stuve-Wiedemann syndrome (SWS) is an extremely rare congenital skeletal disorder associated with significant newborn mortality and morbidity in survivors. Prenatal diagnosis is reportedly possible, but a precise diagnosis is difficult because SWS is part of a heterogeneous group of bone dysplasias. Molecular analysis remains the gold standard for establishing a specific diagnosis of this kind of disorders and for providing effective prenatal counselling. This article presents a case of SWS suspected at prenatal ultrasound in the second trimester of pregnancy and confirmed by multidisciplinary approach at birth. PMID- 17353879 TI - [Rokitansky-Kunster-Hauser-Mayer syndrome: a description of four cases]. PMID- 17353880 TI - Forceps delivery: is it time to stop? PMID- 17353881 TI - Cilostazol in the management of vascular disease. AB - Cilostazol is a potent type III phosphodiesterase inhibitor with pharmacological effects that include vasodilatation, inhibition of platelet activation and aggregation, inhibition of thrombosis, increased blood flow to the limbs, improvement in serum lipids with lowering of triglycerides and elevation of high density lipoprotein cholesterol, and inhibition of vascular smooth muscle cell growth. It operates through its action as endothelium-target antithrombotic therapy, achieving its effects by improving endothelial cell function and reducing the number of platelets partially activated by interacting with activated endothelial cells. Since receiving approval from the Food and Drug Administration in 1999 in the United States for the treatment on intermittent claudication secondary to peripheral arterial disease, new data on its role on the prevention of restenosis after percutaneous transluminal angioplasty and the secondary prevention of cerebral infarction have increased interest in the drug. The aim of this study is to review cilostazol's beneficial effects and adverse events, and to present the results of the major clinical trials. PMID- 17353882 TI - Peripheral arterial revascularization causing parallel increased activity of pro- and anti-inflammatory mediators. AB - AIM: The aim of this study was to investigate the interaction between the proinflammatory mediator interleukin (IL)-6 and anti-inflammatory mediator IL-10 in ischemia reperfusion injury following peripheral arterial revascularization. METHODS: Three groups of patients were recruited (group 1: femoral angiography alone [n=14]; group 2: radiologically successful ilio/femoral angioplasty [n=10]; and group 3: peripheral surgical bypass [n=11]). Peripheral venous blood obtained for all patients at pre-procedure and at 1 h and 24 h post-procedure. After centrifugation supernatant plasma was separated and analysed for proinflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 using enzyme linked immunosorbent assay (ELISA) technique. RESULTS: Levels of IL-6 at 1 and 24 h were significantly higher in group 3 (P<0.05 and P<0.01, respectively) and at 24 h in group 2 as compared to group 1 (P<0.05). Levels of IL-10 were significantly higher in group 3 at 24 h (P<0.05). In group 2 levels of IL-10 higher than group 1, but this did not reach statistical significance (P=0.07). CONCLUSIONS: Raised levels of IL-6 at 1 and 24 h in patients undergoing operative peripheral bypass suggest early and persistent proinflammatory activity, similarly patients with successful angioplasty also demonstrated similar persistent proinflammatory activity of IL-6 at 24 h. Raised levels of IL-10 at 24 h represents anti inflammatory properties of IL-10 counter acting inflammatory response. PMID- 17353883 TI - Acute impairment of the endothelial function by maximal treadmill exercise in patients with intermittent claudication, and its improvement after supervised physical training. AB - AIM: The aim of this study was to determine the effects of maximal exercise and of physical training on endothelial function (EF) of patients with intermittent claudication (IC). METHODS: EF, assessed by ultrasonography of the brachial artery, has been measured in 22 male patients with IC before (pre-exercise EF) and after (postexercise EF) maximal treadmill test. Absolute claudication distance (ACD) and ankle brachial index (ABI) have been measured too. The measurements have been repeated after 18 days (3 times weekly, for 6 weeks) of supervised physical training. RESULTS: Before training, the pre-exercise EF was 7.6+/-2.94 and postexercise EF 5.28+/-3.3 (-33.2%) (P<0.01). After training, the pre-exercise EF was 10.3+/-4.04, whilst postexercise EF was 7.79+/-2.56 (-18.97%) (P<0.01). The differences between the pre-exercise value before and after training and between the postexercise value before and after training were significant (P<0.01). ACD and ABI after training increased respectively from 93.95 to 166.55 m and from 0.67 to 0.71 (P<0.001). CONCLUSIONS: Endothelial dysfunction takes a relevant part in the pathophysiology of IC, with 2/3 of the patients showing an EF lower than the pathological cut-off. Maximal exercise worsens the EF, according to the trend associated with the acute inflammatory response. All these features suggest that physical activity in IC should not utilize the maximal working load, in order to avoid the high inflammatory activation and the acute complications of atherosclerotic plaque. The supervised physical training, besides confirming itself as the most effective means to increase the walking ability, also proved to be able to improve the EF of these patients, as described about other diseases. It is probable that moderate hemodynamic stress reduces the levels of the inflammatory markers and increases the flow-mediated vasodilation through an ischemic preconditioning. The increased walking ability, associated with the improvement of EF could improve the heavy systemic outcome of claudicant patients, as it has been demonstrated in patients with coronary heart disease. Further prospective survival studies on cardiovascular outcomes of trained claudicant patients are needed. PMID- 17353884 TI - Mid-term results of endovascular reconstruction for aorto-iliac obstructive disease. AB - AIM: Aorto-iliac obstructive disease has been traditionally treated with endarterectomy and/or a surgical bypass graft. Kissing-stents technique has been proposed to reconstruct the aorto-iliac bifurcation for complex aorto-iliac lesions. METHODS: We report 43 patients with complex aorto-iliac occlusions managed with endovascular repair. Between March 1999 and October 2005, a total of 43 patients with a mean age of 66+/-10 years underwent endovascular treatment for aorto-iliac obstructive disease. Lesions were classified C (n=34) and D (n=9), accordingly to the Trans-Atlantic Inter-Society Consensus (TASC) classification. All endovascular interventions were performed in the theatre under regional anesthesia. Predilation with kissing-balloons angioplasty was usually performed; the bifurcation was then eventually reconstructed using bilateral stents placed with the kissing technique. Clinical examination and duplex scans or computed tomography-angiography (CT-A) were performed at discharge and 1, 6, and 12 months after the procedure, with yearly studies thereafter. RESULTS: Kissing-stents technique was selectively used in 30 cases (69.7%); the remainder cases were treated with kissing-balloons. Major complications occurred in 2 patients (4.6%). Overall, mean hospitalization was 4.1+/-2.8 days (median 3 days). Mean follow-up was 32.4 months (range 1-84 months; median 36 months). During the follow-up, 2 patients (4.6%) died. Duplex and/or CT-A examination detected 4 re-occlusions. Primary patency rates at 12, 24, and 60 months were 92%, 85.7%, and 80.7%, respectively; overall secondary patency rate was 40/43 patients. CONCLUSIONS: We consider this approach most appropriate for patients deemed at high operative risk for conventional repair or for those who refuse surgery. PMID- 17353885 TI - A case control study between diabetic and non-diabetic subjects with ischemic stroke. AB - AIM: The clinical and prognostic profile of diabetic stroke patients is still an unclarified topic. The aim of the present study is to compare clinical features and risk factor profile in diabetics and in non-diabetics affected by acute ischemic stroke. METHODS: We have included 98 diabetics and 102 matched non diabetic subjects affected by acute ischemic stroke and matched by age (+/-3 years) and gender. We determined the Scandinavian Stroke Scale (SSS) on admission and the Rankin disability scale on discharge and after a 6 months follow-up. Ischemic stroke has been classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. We anamnestically evaluated the presence of hypertension, hypercholesterolemia, any records of transient ischemic attack, and stroke. Using conditional logistic regression analysis, we calculated adjusted odds ratio (OR) and 95% confidence interval (CI). RESULTS: Diabetes was associated with lacunar ischemic stroke subtype (OR 3.89, 95% CI 2.23-6.8), with a record of hypertension (OR 2.53, 95% CI 1.48-4.32), and with a better SSS score at admission (OR 0.58, 95% CI 0.36-0.96). The association of diabetes with lacunar stroke remained significant also after adjustment for hypertension (adjusted OR 3.37, 95% CI 1.9-5.99) or for large artery atherosclerotic and cardioembolic stroke subtypes (adjusted OR 2.69, 95% CI 1.08-6.69). CONCLUSIONS: Our study shows some significant differences in acute ischemic stroke among diabetics in comparison with non-diabetics (higher frequency of hypertension, higher prevalence of lacunar stroke subtype, lower neurological deficit at admission in diabetics). PMID- 17353886 TI - Prevalence of peripheral arterial disease and prior stroke in octogenarians with symptomatic severe aortic stenosis or severe coronary artery disease: influence in management and outcome. AB - AIM: Severe aortic stenosis (SAS) and severe coronary artery disease (SCAD) are the most frequent reasons to perform cardiac surgery in octogenarians. Non coronary vascular disease is frequently present in these patients. METHODS: We assessed the prevalence and impact of previous stroke (PS) and peripheral arterial disease (PAD) on the management and outcome of 130 consecutive symptomatic patients (80 years old with SAS or SCAD. RESULTS: Mean age was 82.8+/ 3.1 years. PS was present in 24 patients (18.5%) and PAD in 15 (11.5%). We found a non-significant trend to a higher prevalence of PAD in patients with SCAD than in patients with SAS (14.5% vs 6.4%, P=0.13), while no relevant differences were seen for PS prevalence (19.3% vs 17%, P=0.75). Patients with PS tended to be operated less frequently than patients without PS (20.8% vs 37.7%, P=0.08), while no relevant differences were seen for patients with and without PAD (26.7% vs 35.7%, P=0.5). Thirty-nine patients (30%) died during follow-up, mean of 1.1(0.7 years (median 1 years; 100% complete). There was a trend to a worse prognosis in patients with PAD (adjusted hazard ratio [HR] 2.2; 95% confidence interval [CI] 0.96-4.8; P=0.06), while PS showed no independent influence on survival (adjusted HR 1.3, 95% CI 0.6-2.8, P=0.53). CONCLUSIONS: PS and PAD are frequently present in octogenarians with SAS or SCAD. Patients with PS show a similar long-term mortality, but tend to be operated less frequently. On the other hand, PAD did not influence the decision of surgical treatment, but is associated with a lower survival rate. PMID- 17353887 TI - Morphological features and apoptosis in the left internal thoracic artery grafts before implantation. AB - AIM: A small number of left internal thoracic artery (LITA) grafts are occluded at 3 years after the operation or show more than 50% stenosis of the lumen. The purpose of this study is to examine factors related to the morphology of the wall and to the function of the cell population of LITA grafts before implantation, in order to evaluate their quality and the viability, in a follow-up examination. METHODS: Fifteen LITA grafts were examined with light microscopy, for their morphology, endothelial cell coverage, apoptosis and cell proliferation, scanning electron microscopy and transmission electron microscopy. RESULTS: Increase of the thickness of the intima (14.21+/-1.28 mm), mean thickness of media 160.37+/ 11.97 mm, detachment of intima from media, presence of foam cells in the media, low endothelial coverage (40.638+/-16.864), increase of apoptosis in intima (46.38+/-13.46), sub-intima (29.3+/-8.54), media (34.91+/-6.05) and adventitia (40.21+/-5.36), blood cells penetration of the intima through disruptions between endothelial cells are findings of LITA grafts before implantation. Cell proliferation was not detected in the wall of any graft. Follow-up examination 6 months and 2.5 years after the operation showed normal function of LITA grafts. CONCLUSIONS: Besides of the wall injury and the initiated atherosclerotic lesions, LITA grafts are well functioning at the time of the follow-up examination. Maybe our findings are related to the later occlusion of the referred in the literature small number of LITA grafts. PMID- 17353888 TI - Changing patterns in the etiology of acute lower limb ischemia. AB - AIM: The aim of this study was to examine the causes of acute lower limb ischemia (ALLI) in a major referral center in Greece. METHODS: Hospital records of patients that were admitted with ALLI between January 1, 2000 and December 31, 2004, were retrospectively reviewed for this purpose. A total of 440 cases of ALLI in 351 patients were identified. RESULTS: In 174 (39.54%) cases, the ischemia was attributed to embolism; in 221 (50.23%) to thrombosis and in the remaining 45 (10.23%) to less common causes of ALLI (trauma [iatrogenic and non], vasculitis, dissection). Of 174 cases of embolism, 136 (78.16%) were of cardiac origin, 22 (12.64%) were due to non-cardiac emboli, while in the remaining 16 cases (9.2%) no specific origin of embolism was found. Of 221 cases of thrombosis 66 (29.86%) concerned native arterial thrombosis, while 155 (70.14%) concerned postinterventional thrombosis, including 144 (65.16%) cases of bypass graft thrombosis and 11 (4.98%) cases of iliac or femoral stent thrombosis. Sixty patients were admitted more than once with ALLI, most commonly due to repeated bypass graft thrombosis (85%). The latter was diagnosed in 32.73% of all ALLI cases and presented more often than native arterial thrombosis by a ratio of approximately 2.2:1. CONCLUSION: This study indicates that currently the leading cause for hospital admissions in patients with ALLI is thrombosis which most commonly occurs in bypass grafts rather than in native arteries. PMID- 17353889 TI - Spontaneous recanalization in deep venous thrombosis: a prospective duplex ultrasound study. AB - AIM: The aim of this study was to evaluate the dynamics of the recanalization process (spontaneous fibrinolysis) in completely occlusive deep venous thrombosis (DVT) using duplex ultrasound examination and to investigate the influence of different factors on the evolution of thrombus regression. METHODS: This longitudinal prospective study was done with 74 consecutive patients with completely occlusive acute multilevel DVT, confirmed by echo duplex scan after 1, 3, 6, and 12 months. At each re-evaluation, the degree and the type of recanalization were determined. Efficacy of tinzaparin (175 IU/kg, s.c., q.d. for 7-14 days) and continued with warfarin (12 months at INR 2-3) as well as patients' compliance with compressive elastic hosiery wearing were carefully followed. Relationship between the degree and pattern of recanalization and patients' age, gender, as well as thrombosis etiology and location were determined. RESULTS: Sixty-four patients completed the study. The mean recanalization rate was 39.7% at 1, 64.8% at 3, 82% at 6, and 90.3% at 12 months. Marginal recanalization was more frequently observed, but recanalization pattern was changing during follow-up. CONCLUSIONS: In the case of efficient anticoagulant and compressive therapy, the spontaneous recanalization process of DVT is important from the very first month of evolution, but an almost complete re-permeabilization is observed only after 12 months of treatment. The unilocular, marginal pattern of thrombus lysis is often observed and has better evolution than the multilocular cavernous one. The dynamics of recanalization are characterized by distal-to-proximal extension and in the first 6 months are significantly influenced by patient's gender and thrombosis etiology. PMID- 17353890 TI - Profuse bleeding in patients with chronic venous insufficiency. AB - AIM: The aim of this retrospective study was to compare the healing rates of patients where the bleeding points were sutured (n=52) against those where the bleeding was controlled using compression sclerotherapy (n=72). The incidence of re-bleeding was also followed over a 12-month period. METHODS: During 1999-2003, we treated 124 patients (86 women and 38 men; mean age: 64 years, age range: 36 85 years) with profuse bleeding from varicose veins as emergency cases. Seventy two patients (58%) were treated with compression sclerotherapy. In the suture group of 52 patients (42%) the bleeding points were treated in the emergency outpatients department. Usually a cross stitch was used and the same type of uninterrupted compression as in the sclerotherapy group was applied for 6 weeks afterwards. RESULTS: In the group of patients where compression sclerotherapy (Fegan's method) was used to control the bleeding (65 patients), the average time taken for the wound to heal completely was 7 days (5-13 days). There was no recurrence of bleeding in the subsequent 12 months. In the group of patients where a suture was used to control the bleeding, the average time of healing was 14 days (11-19 days) and re-bleeding occurred in 12 cases (23%). CONCLUSIONS: Using Fegan's technique of compression sclerotherapy with a low concentration of sclerosant (0.2% sodium tetradecyl sulfate), it is possible to treat bleeding varicose veins effectively with significantly faster healing of the wound. PMID- 17353891 TI - Prevalence of lower extremity venous disease in inflammatory bowel disease. AB - AIM: Inflammatory bowel disease (IBD) has long been considered a risk factor for venous thromboembolism (VTE). Whereas most patients have persistent venous valvular dysfunction following lower extremity deep venous thrombosis (DVT), we hypothesized that patients with IBD would have an increased prevalence of valvular incompetence and changes of chronic DVT (reduced venous caliber with thickened walls) relative to patients with irritable bowel syndrome (IBS) or normal volunteers. METHODS: Subjects with confirmed IBD, clinical features of IBS or normal volunteers underwent complete, prospective duplex ultrasound assessment of their lower extremity venous vascular system. The sonographer performing the venous study was blinded to the clinical diagnosis of the patients. Valvular incompetence was graded as mild, moderate or severe based on accepted criteria. RESULTS: Eighty patients with IBD (ulcerative colitis, UC: 66; Crohn's disease: 14), 80 patients with IBS, and 80 healthy volunteers agreed to participate. One patient with UC was found to have non-occlusive chronic DVT within the left superficial femoral vein. Mild and moderate valvular incompetence was evenly distributed between the 3 groups. No patients met criteria for either acute DVT or severe venous incompetence. CONCLUSION: In patients with IBD, neither valvular incompetence nor chronic venous obstruction are over-represented compared to patients with IBS or normal volunteers. In this prospective assessment of venous physiology by duplex ultrasound, we were not able to confirm prior reports that IBD is a major risk factor for VTE. PMID- 17353892 TI - Carotid artery false aneurysm caused by blunt trauma. A case report. AB - Different mechanisms of blunt trauma producing carotid artery false aneurysms are described in literature. We report one such case caused by combination of two mechanisms: accidental hyperextension of the neck, and subsequent sudden forceful hit by a ball during the water polo match. PMID- 17353893 TI - Case report of adventitial cystic disease of the popliteal artery presented with the ''dog-leg'' sign. AB - Adventitial cystic disease of the popliteal artery constitutes an infrequent cause of claudication in non-atherosclerotic young or middle-aged population. Here, we report the case of a 43-year-old female with adventitial cystic disease of the popliteal artery causing left lower leg claudication, detected by duplex scanning. The angio-CT showed the "dog-leg" sign, typical of the aneurysm of the popliteal artery. Surgery was performed through the posterior approach. The cyst and the affected segment of the artery were successfully excised and replaced with an autogenous saphenous vein graft. In 1 year follow-up the graft is patent and the patient is completely asymptomatic. PMID- 17353894 TI - Genome-wide functional analysis of pathogenicity genes in the rice blast fungus. AB - Rapid translation of genome sequences into meaningful biological information hinges on the integration of multiple experimental and informatics methods into a cohesive platform. Despite the explosion in the number of genome sequences available, such a platform does not exist for filamentous fungi. Here we present the development and application of a functional genomics and informatics platform for a model plant pathogenic fungus, Magnaporthe oryzae. In total, we produced 21,070 mutants through large-scale insertional mutagenesis using Agrobacterium tumefaciens-mediated transformation. We used a high-throughput phenotype screening pipeline to detect disruption of seven phenotypes encompassing the fungal life cycle and identified the mutated gene and the nature of mutation for each mutant. Comparative analysis of phenotypes and genotypes of the mutants uncovered 202 new pathogenicity loci. Our findings demonstrate the effectiveness of our platform and provide new insights on the molecular basis of fungal pathogenesis. Our approach promises comprehensive functional genomics in filamentous fungi and beyond. PMID- 17353895 TI - Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy. AB - Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases. PMID- 17353896 TI - The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. AB - The autosomal recessive disorder Shwachman-Diamond syndrome, characterized by bone marrow failure and leukemia predisposition, is caused by deficiency of the highly conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein. Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. Thus, our data link defective late 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition. PMID- 17353897 TI - Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis. AB - Neural progenitor proliferation and migration influence brain size during neurogenesis. We report an autosomal recessive microcephaly syndrome cosegregating with a homozygous balanced translocation between chromosomes 3p and 10q, and we show that a position effect at the breakpoint on chromosome 3 silences the eomesodermin transcript (EOMES), also known as T-box-brain2 (TBR2). Together with the expression pattern of EOMES in the developing human brain, our data suggest that EOMES is involved in neuronal division and/or migration. Thus, mutations in genes encoding not only mitotic and apoptotic proteins but also transcription factors may be responsible for malformative microcephaly syndromes. PMID- 17353898 TI - EGFR kinase domain mutations - functional impact and relevance for lung cancer therapy. AB - In 2004 remarkable clinical responses in non-small-cell lung cancer (NSCLC) patients treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib were reported to correlate with the presence of certain somatic EGFR kinase domain mutations in tumors. Since then, a surge of enthusiasm has been encountered in the field of molecular and clinical oncology. Beyond the promise of a tailored medicine, questions about the molecular mechanisms underlying the observed effects have arisen. In vitro analysis of NSCLC cells with endogenous EGFR mutations, recombinant expression of EGFR variants by transfection of several cell lines and the generation of transgenic mice expressing mutant EGFR were applied to study the impact of these genetic alterations on cellular signaling and cell fate. This review outlines the current mechanistic knowledge derived from such studies and discusses the relevance of EGFR kinase domain mutations for EGFR-directed therapies, including monoclonal antibodies. PMID- 17353899 TI - Downregulation of Bfl-1 protein expression sensitizes malignant B cells to apoptosis. AB - Elevated expression of the antiapoptotic protein Bfl-1 (A1) was previously reported in several cancer cell lines. Recently, molecular profiling of large B cell lymphoma identified Bfl-1 as a gene signature in 'OxPhos' diffuse large B cell lymphoma subtype and in primary mediastinal large B-cell lymphoma, suggesting that in addition to Bcl-2, Bcl-xL and Mcl-1, Bfl-1 may be a relevant target in the design of new strategies for cancer therapy. Using short hairpin RNA strategy, we show here that Bfl-1 silencing in one lymphoblastoid B-cell line and in two diffuse large B-cell lymphoma cell lines potently induces their apoptosis and sensitizes those cell lines to anti-CD20 (Rituximab)-mediated cell death as well as to apoptosis induced by chemotherapeutic molecules such as doxorubicin, vincristine, cisplatin and fludarabine. These results demonstrate for the first time that Bfl-1 is an essential protein for survival of malignant B cells and suggest Bfl-1 may represent a potential target for future drug development against B cell lymphoma. PMID- 17353900 TI - Genome-wide single-nucleotide polymorphism analysis in juvenile myelomonocytic leukemia identifies uniparental disomy surrounding the NF1 locus in cases associated with neurofibromatosis but not in cases with mutant RAS or PTPN11. AB - Juvenile myelomonocytic leukemia (JMML) is a malignant hematopoietic disorder whose proliferative component is a result of RAS pathway deregulation caused by somatic mutation in the RAS or PTPN11 oncogenes or in patients with underlying neurofibromatosis type 1 (NF-1), by loss of NF1 gene function. To search for potential collaborating genetic abnormalities, we used oligonucleotide arrays to analyse over 116 000 single-nucleotide polymorphisms across the genome in 16 JMML samples with normal karyotype. Evaluation of the SNP genotypes identified large regions of homozygosity on chromosome 17q, including the NF1 locus, in four of the five samples from patients with JMML and NF-1. The homozygous region was at least 55 million base pairs in each case. The genomic copy number was normal within the homozygous region, indicating uniparental disomy (UPD). In contrast, the array data provided no evidence for 17q UPD in any of the 11 JMML cases without NF-1. We used array-based comparative genomic hybridization to confirm 17q disomy, and microsatellite analysis was performed to verify homozygosity. Mutational analysis demonstrated that the inactivating NF1 lesion was present on both alleles in each case. In summary, our data indicate that a mitotic recombination event in a JMML-initiating cell led to 17q UPD with homozygous loss of normal NF1, provide confirmatory evidence that the NF1 gene is crucial for the increased incidence of JMML in NF-1 patients, and corroborate the concept that RAS pathway deregulation is central to JMML pathogenesis. PMID- 17353901 TI - Micronodular transformation as a novel mechanism of VEGF-A-induced metastasis. AB - How and why tumors metastasize is still a matter of debate. The assumption is that mutations render tumor cells with a metastatic phenotype, enabling entrance in and transport through lymph or blood vessels. Distant outgrowth is thought to occur only in a suitable microenvironment (the seed and soil hypothesis). However, the anatomical location of most metastases in cancer patients suggests entrapment of tumor cells in the first microcapillary bed that is encountered. We here investigated how vascular endothelial growth factor-A (VEGF-A) attributes to the metastatic process. We describe here that VEGF-A enhances spontaneous metastasis by inducing intravasation of heterogeneous tumor cell clusters, surrounded by vessel wall elements, via an invasion-independent mechanism. These tumor clusters generate metastatic tissue embolisms in pulmonary arteries. Treatment of tumor-bearing mice with the antiangiogenic compound ZD6474 prevented the development of this metastatic phenotype. This work shows that tumors with high constitutive VEGF-A expression metastasize via the formation of tumor emboli and provides an alternative rationale for anti-VEGF-A therapy, namely to inhibit metastasis formation. PMID- 17353902 TI - Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells. AB - The hedgehog (Hh) signaling pathway regulates progenitor cells during embryogenesis and tumorigenesis in multiple organ systems. We have investigated the activity of this pathway in adult gliomas, and demonstrate that the Hh pathway is operational and activated within grade II and III gliomas, but not grade IV de novo glioblastoma multiforme. Furthermore, our studies reveal that pathway activity and responsiveness is confined to progenitor cells within these tumors. Additionally, we demonstrate that Hh signaling in glioma progenitor cells is ligand-dependent and provide evidence documenting the in vivo source of Sonic hedgehog protein. These findings suggest a regulatory role for the Hh pathway in progenitor cells within grade II and III gliomas, and the potential clinical utility of monitoring and targeting this pathway in these primary brain tumors. PMID- 17353903 TI - Enhanced tumorigenicity of fibroblasts transformed with human herpesvirus 8 chemokine receptor vGPCR by successive passage in nude and immunocompetent mice. AB - The human herpes virus 8 (HHV-8)-encoded G protein-coupled chemokine receptor (vGPCR) has been implicated in the pathogenesis of Kaposi's sarcoma (KS), particularly because of its high constitutive signaling activity. Here, we used retroviral transduction to generate vGPCR-expressing 3T3 fibroblasts that are tumorigenic in nude mice, but as expected fail to induce tumors in their immunocompetent counterparts. However, tumor fragments obtained from nude mice grow progressively in immunocompetent BALB/c mice. Unexpectedly, vGPCR-expressing cells established from grafted tumor fragments gave rise to tumors in immunocompetent mice. These tumors exhibit a striking histological resemblance to KS including plump spindle cell morphology, a high degree of vascularization and brisk mitotic activity. High expression of vGPCR was confirmed in the cell lines and tumors using a newly developed vGPCR-specific monoclonal antibody. Finally, short interfering RNA directed at vGPCR abrogated or significantly delayed tumorigenesis in mice, demonstrating that the tumor development is specifically driven by vGPCR. This novel model for vGPCR-mediated oncogenesis will contribute to our understanding of the role of vGPCR in the pathogenesis of HHV-8 and may even be important in identifying critical molecular and epigenetic changes during tumor progression in vivo. PMID- 17353904 TI - Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport. AB - A major obstacle to successful chemotherapy is intrinsic or acquired multi-drug resistance (MDR). The most common cause of MDR involves increased drug efflux from cancer cells mediated by members of the ATP-binding cassette (ABC) transporter family. The regulation of ABC transporters in the context of cancer is poorly understood, and clinical efforts to inhibit their function have not been fruitful. Constitutive activation of the Hedgehog (Hh) pathway has been shown to contribute to the growth and maintenance of various cancers. Here, we show that inhibition of Hh signaling increases the response of cancer cells to multiple structurally unrelated chemotherapies. We further show that Hh pathway activation induces chemoresistance in part by increasing drug efflux in an ABC transporter-dependent manner. We found that Hh signaling regulates the expression of the ABC transporter proteins multi-drug resistance protein-1 (MDR1, ABCB1, P glycoprotein) and (BCRP, ABCG2), and that targeted knockdown of MDR1 and BCRP expression by small interfering RNA partially reverses Hh-induced chemoresistance. These results suggest that the Hh pathway may be a target to overcome MDR and increase chemotherapeutic response. PMID- 17353905 TI - DFF45/ICAD restores cisplatin-induced nuclear fragmentation but not DNA cleavage in DFF45-deficient neuroblastoma cells. AB - We have previously defined a homozygously deleted region at chromosome 1p36.2 p36.3 in human neuroblastoma cell lines, NB-1 and NB-C201, and identified six genes including DFF45/ICAD within this region. In this study, we found that NB C201 cells are much more resistant to various genotoxic stresses such as cisplatin (CDDP) than CHP134 and SH-SY5Y cells that do not have the homozygous deletion. To examine a role(s) of DFF45 in the regulation of apoptosis in response to CDDP, we have established stably DFF45-expressing NB-C201 cell clones (DFF45-1 and DFF45-3) and a control cell clone (NB-C201-C) using a retrovirus mediated gene transfer. In contrast to NB-C201-C cells, DFF45-3 cells displayed apoptotic nuclear fragmentation in response to CDDP. Although CDDP-induced proteolytic cleavage of procaspase-3 and DFF45 in DFF45-3 cells, we could not detect a typical apoptotic DNA fragmentation. Additionally, deletion analysis revealed that C-terminal region of DFF45 is required for inducing nuclear fragmentation. Unexpectedly, (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assays demonstrated that DFF45 has undetectable effect on CDDP sensitivity of NB-C201 cells. Taken together, our present results suggest that DFF45/DFF40 system may be sufficient for CDDP-induced nuclear fragmentation but not DNA cleavage. PMID- 17353906 TI - Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins. AB - Cancer cells display an altered distribution of DNA methylation relative to normal cells. Certain tumor suppressor gene promoters are hypermethylated and transcriptionally inactivated, whereas repetitive DNA is hypomethylated and transcriptionally active. Little is understood about how the abnormal DNA methylation patterns of cancer cells are established and maintained. Here, we identify over 20 DNMT3B transcripts from many cancer cell lines and primary acute leukemia cells that contain aberrant splicing at the 5' end of the gene, encoding truncated proteins lacking the C-terminal catalytic domain. Many of these aberrant transcripts retain intron sequences. Although the aberrant transcripts represent a minority of the DNMT3B transcripts present, Western blot analysis demonstrates truncated DNMT3B isoforms in the nuclear protein extracts of cancer cells. To test if expression of a truncated DNMT3B protein could alter the DNA methylation patterns within cells, we expressed DNMT3B7, the most frequently expressed aberrant transcript, in 293 cells. DNMT3B7-expressing 293 cells have altered gene expression as identified by microarray analysis. Some of these changes in gene expression correlate with altered DNA methylation of corresponding CpG islands. These results suggest that truncated DNMT3B proteins could play a role in the abnormal distribution of DNA methylation found in cancer cells. PMID- 17353907 TI - Oncogenic tyrosine kinase NPM/ALK induces activation of the rapamycin-sensitive mTOR signaling pathway. AB - The mechanisms of cell transformation mediated by the nucleophosmin (NPM)/anaplastic lymphoma kinase (ALK) tyrosine kinase are only partially understood. Here, we report that cell lines and native tissues derived from the NPM/ALK-expressing T-cell lymphoma display persistent activation of mammalian target of rapamycin (mTOR) as determined by phosphorylation of mTOR targets S6rp and 4E-binding protein 1 (4E-BP1). The mTOR activation is serum growth factor independent but nutrient-dependent. It is also dependent on the expression and enzymatic activity of NPM/ALK as demonstrated by cell transfection with wild-type and functionally deficient NPM/ALK, small interfering RNA (siRNA)-mediated NPM/ALK depletion and kinase activity suppression using the inhibitor WHI-P154. The NPM/ALK-induced mTOR activation is transduced through the mitogen-induced extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway and, to a much lesser degree, through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Accordingly, whereas the low-dose PI3K inhibitor wortmannin and Akt inhibitor III profoundly inhibited Akt phosphorylation, they had a very modest effect on S6rp and 4E-BP1 phosphorylation. In turn, MEK inhibitors U0126 and PD98059 and siRNA-mediated depletion of either ERK1 or ERK2 inhibited S6rp phosphorylation much more effectively. Finally, the mTOR inhibitor rapamycin markedly decreased proliferation and increased the apoptotic rate of ALK+TCL cells. These findings identify mTOR as a novel key target of NPM/ALK and suggest that mTOR inhibitors may prove effective in therapy of ALK-induced malignancies. PMID- 17353908 TI - Frequent loss of SFRP1 expression in multiple human solid tumours: association with aberrant promoter methylation in renal cell carcinoma. AB - Oncogenic wingless-related mouse mammary tumour virus (Wnt) signalling, caused by epigenetic inactivation of specific pathway regulators like the putative tumour suppressor secreted frizzled-related protein 1 (SFRP1), may be causally involved in the carcinogenesis of many human solid tumours including breast, colon and kidney cancer. To evaluate the incidence of SFRP1 deficiency in human tumours, we performed a large-scale SFRP1 expression analysis using immunohistochemistry on a comprehensive tissue microarray (TMA) comprising 3448 tumours from 36 organs. This TMA contained 132 different tumour subtypes as well as 26 different normal tissues. Although tumour precursor stages of, for example kidney, colon, endometrium or adrenal gland still exhibited moderate to abundant SFRP1 expression, this expression was frequently lost in the corresponding genuine tumours. We defined nine novel tumour entities with apparent loss of SFRP1 expression, i.e., cancers of the kidney, stomach, small intestine, pancreas, parathyroid, adrenal gland, gall bladder, endometrium and testis. Renal cell carcinoma (RCC) exhibited the highest frequency of SFRP1 loss (89% on mRNA level; 75% on protein level) and was selected for further analysis to investigate the cause of SFRP1 loss in human tumours. We performed expression, mutation and methylation analysis in RCC and their matching normal kidney tissues. SFRP1 promoter methylation was frequently found in RCC (68%, n=38) and was correlated with loss of SFRP1 mRNA expression (p<0.05). Although loss of heterozygosity was found in 16% of RCC, structural mutations in the coding or promoter region of the SFRP1 gene were not observed. Our results indicate that loss of SFRP1 expression is a very common event in human cancer, arguing for a fundamental role of aberrant Wnt signalling in the development of solid tumours. In RCC, promoter hypermethylation seems to be the predominant mechanism of SFRP1 gene silencing and may contribute to initiation and progression of this disease. PMID- 17353909 TI - Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition. AB - Pituitary tumor transforming gene (PTTG1) was isolated from rat pituitary tumor cells, and subsequently identified as a securin protein as well as a transcription factor. We show here a global transcriptional effect of PTTG1 in human choriocarcinoma JEG-3 cells by simultaneously assessing 20,000 gene promoters using chromatin immunoprecipitation (ChIP)-on-Chip experiments. Seven hundred and forty-six gene promoters (P<0.001) were found enriched, with functions relating to cell cycle, metabolic control and signal transduction. Significant interaction between PTTG1 and Sp1 (P<0.000001) was found by transcriptional pattern analysis of ChIP data and further confirmed by immunoprecipitation and pull-down assays. PTTG1 acts coordinately with Sp1 to induce cyclin D3 expression approximately threefold, and promotes G1/S-phase transition independently of p21. PTTG1 deletion was also protective for anchorage independent cell colony formation. The results show that PTTG1 exhibits properties of a global transcription factor, and specifically modulates the G1/S phase transition by interacting with Sp1. This novel signaling pathway may be required for PTTG1 transforming activity. PMID- 17353910 TI - Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol. AB - The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults. PMID- 17353912 TI - Patterns of gene expression in the limbic system of suicides with and without major depression. AB - The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides=18, non depressed suicides=8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression. PMID- 17353911 TI - A role for SC35 and hnRNPA1 in the determination of amyloid precursor protein isoforms. AB - The beta-amyloid peptide (Abeta) that accumulates in senile plaques in Alzheimer's disease is formed by cleavage of the amyloid precursor protein (APP). The APP gene has several intronic Alu elements inserted in either the sense or antisense orientation. In this study, we demonstrate that binding of SC35 and hnRNPA1 to Alu elements on either side of exon 7 in the transcribed pre-mRNA is involved in alternative splicing of APP exons 7 and 8. Neuronal cells transfected with the full-length form of APP secrete higher levels of Abeta than cells transfected with the APP695 isoform lacking exons 7 and 8. Finally, we show that treatment of neuronal cells with estradiol results in increased expression of APP695, SC35 and hnRNPA1, and lowers the level of secreted Abeta. An understanding of the regulation of splicing of APP may lead to the identification of new targets for treating Alzheimer's disease. PMID- 17353913 TI - Changes in nitric oxide synthase expression in young and adult rats after spinal cord injury. AB - OBJECTIVE: To examine the clinical meaning of the changes in nitric oxide synthase (NOS) expression and activity after spinal cord injury (SCI) according to the age of the experiment animal. MATERIAL AND METHOD: Ten 5- and 16-week-old Sprague-Dawley rats were laminectomized at T10 and SCI induced at this level using a New York impactor. Outcome measures to assess SCI utilized the Basso Beatti-Bresnahan scale to quantitate hind limb motor dysfunction as a functional outcome measure. NOS isoforms (nNOS, neuronal NOS; iNOS, inducible NOS; and eNOS, endothelial NOS) were also immunolocalized in sections of control and spinal cord injury in the two sample groups using specific monoclonal antibodies. Student's t test evaluated the difference between the young and adult rats, and P<0.05 was considered as significant value. RESULT: As the expression of nNOS on the spinal gray matter of the adult rat decreased, eNOS activity increased. Different from the adult rat, expression of the nNOS in the young rat was maintained until 1 day after SCI, and compared with the adult rat; eNOS activity was increased in the vessels from the damaged gray matter area after 7 days of SCI. iNOS expression was maintained until the 7th day of SCI on the adult rat, but iNOS expression after 7 days of SCI on young rat decreased. The young rat showed relatively less motor disability on the hind limb when compared with the adult rat, and had a rapid recovery. CONCLUSION: Neural protective eNOS activity increased after SCI in the young rat, and neural destructive iNOS expression was more remarkable in the adult rat. PMID- 17353914 TI - Point-of-care PSA testing: an evaluation of PSAwatch. AB - We present a new quantitative prostate-specific antigen (PSA) assay using a portable, point-of-care test (PSAwatch) and reader system (BioScan) for measuring PSA concentrations in the range from 0.5 to < or =25 microg/l. Blood samples from patients (n=199) were submitted for laboratory PSA and also evaluated using PSAwatch and the BioScan system. PSA concentrations in 188 men were < or =25 microg/l and studied. Correlation between the two methods was good (R(2)=0.88) with a standard error of 1.588. The regression line had a bias of -0.02 at the concentration of 4.00 microg/l. This is the first report of a quantitative, portable, point-of-care PSA test and reader system. PSAwatch may reduce the number of hospital visits for patients with prostate disease. PMID- 17353915 TI - Incidental diagnosis of a PSA-negative prostate cancer by 18FDG PET/CT in a patient with hypopharyngeal cancer. AB - Diagnosis of prostate cancer (PC) still remains critical as non-invasive screening with prostate specific-antigen (PSA) lacks to indicate malignancy of the prostate in some cases. Recent research has shown that clinically meaningful PC can develop in patients with a PSA value <4 ng/ml, frequently defined as upper limit of normal serum PSA levels. Furthermore, both morphological (computed tomography (CT), magnetic resonance imaging, transrectal ultrasound) and functional imaging with (18)fluorodeoxyglucose positron emission tomography (FDG PET) are associated with several limitations for primary diagnosis of PC. We report a case of an incidentally diagnosed PSA-negative PC by (18)FDG PET/CT in a patient with a previous diagnosis of a hypopharyngeal cancer. PMID- 17353916 TI - Patient satisfaction with nurse-led telephone consultation for the follow-up of patients with prostate cancer. AB - Prostate cancer is being diagnosed earlier and in higher numbers than ever before. The nature of the disease means many patients have to be monitored regularly and for a prolonged period leading to increased pressure on urology outpatient resources and inconvenience for the patient. Here we investigate patient satisfaction with a nurse-led telephone-based follow-up clinic and compare it to satisfaction with traditional outpatient consultations. A Consultation Satisfaction Questionnaire (CSQ) evaluating four domains, namely General Satisfaction (GS), Professional Care (PC), Depth of Relationship (DR) and Perceived Time (PT) was used to assess satisfaction in three groups. Group 1 consisted of 299 patients attending the outpatient department before commencing telephone consultations; Group 2 consisted of 163 men attending outpatients after commencement of the telephone consultations; and Group 3 was the telephone group (234 men). We demonstrated no significant difference in GS or PC between Group 1 and Group 3 or Group 2 and Group 3, although DR and PT was significantly lower in the telephone group compared with Group 1. We also found that waiting times were significantly shorter in the telephone group. In conclusion, telephone follow-up appears to be an acceptable alternative to outpatient follow-up in terms of GS and PC and appears to be more convenient for the patient, although these benefits come at the expense of loss of DR and PT with the clinician. PMID- 17353917 TI - High-level amplification at 17q23 leads to coordinated overexpression of multiple adjacent genes in breast cancer. AB - Increased copy numbers of 17q23 chromosomal region have been shown to occur in different tumour types and to be associated with tumour progression and with poor prognosis. Several genes have earlier been proposed as potential oncogenes at this region largely on the grounds of cell lines studies. In this study, we performed a systematic gene expression survey on 26 primary breast tumours with known 17q23 amplification status by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). The 17q23 amplicon is restricted to an approximately 5 MB region in breast cancer and contains 29 known genes. Our survey revealed a statistically significant (P<0.01) difference between the high level and no amplification groups in a set of eleven genes whereas no difference between the moderate and the non-amplified tumour groups were observed. Interestingly, these 11 genes were located adjacent to one another within a 1.56 Mb core region in which all except one of the genes were overexpressed. These data suggest that only high-level amplification at the 17q23 amplicon core leads to elevated gene expression in breast cancer. Moreover, our results highlight the fact that 17q23 amplicon carries multiple candidate genes and that this may be a more common event in gene amplification than previously thought. PMID- 17353918 TI - Mitomycin C and Vinorelbine for second-line chemotherapy in NSCLC--a phase II trial. AB - Single-agent therapy with Docetaxel or Pemetrexed is the current therapy of choice for second-line treatment in advanced non-small-cell lung cancer (NSCLC). The role of older agents was underattended over the last years. This study presents the combination of Mitomycin C and Vinorelbine in pretreated patients. Forty-two patients (stage IIIB and IV, pretreated with platinum-based chemotherapy) received 8 mg m(-2) Mitomycin C on day 1 and 25 mg m(-2) Vinorelbine on days 1 and 8 of a 28-day cycle. End points were objective tumour response, survival, and toxicity. Additionally, quality of life (QoL) was assessed. Five patients (11.9 %) achieved partial responses and 13 patients (31.9%) stable disease. Progression-free survival was 16 weeks. The median overall survival was 8.5 month. Eleven patients (26.2 %) suffered from grade 3 or 4 neutropenia and four patients (9.52%) from grade 3 or 4 anaemia. Evaluation of QoL showed that some items ameliorated during therapy. The therapeutic concept including Mitomycin C and Vinorelbine offers an efficacious and well-tolerated regimen, with relatively low toxicity. Objective response and survival data correlate with other second-line studies using different medication. As costs of Mitomycin C and Vinorelbine are lower compared with current drugs of choice, this regimen is likely to be cost-saving. PMID- 17353919 TI - Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. AB - Vascular endothelial cell growth factors (VEGF)-A, -C and -D have potent angio and lymphangiogenic functions in experimental models, although their role in the progression of human breast cancer is unclear. The aims of the current study were to examine the relationship between the expression of the aforementioned growth factors with the angio and lymphangiogenic characteristics of breast cancer, and to assess their suitability as potential prognostic factors. Paraffin-embedded sections of 177 primary invasive breast cancer, with complete clinical follow-up information for 10 years, were stained for VEGF-A, -C, -D, podoplanin and CD34 using standard immunohistochemical approaches. The expression of the growth factors was correlated with clinicopathological criteria and patients' survival. Lymph vessel density (LVD) and microvessel density (MVD) were assessed and correlated with expression of the growth factors. Vascular endothelial cell growth factor-A, -C and -D were highly expressed in 40, 37 and 42% of specimens, respectively. High expression of VEGF-A and - C, but not of -D, was associated with a higher LVD (P=0.013 and P=0.014, respectively), a higher MVD (P<0.001 and P=0.002, respectively), the presence of lymph node metastasis (P<0.001 and P<0.001, respectively), distant metastasis (P=0.010 and P=0.008, respectively) and a shorter Overall Survival (P=0.029 and 0.028, respectively). In conclusion, breast cancers that express high levels of VEGF-A and -C are characterised by a poor prognosis, likely through the induction of angio and lymphangiogenesis. Examination of expression of VEGF-A and -C in breast cancer may be beneficial in the identification of a subset of tumours that have a higher probability of recurrence and metastatic spread. PMID- 17353920 TI - The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases. AB - The nature of the invasive growth pattern and microvessel density (MVD) have been suggested to be predictors of prognosis in primary colorectal cancer (CRC) and colorectal liver metastases. The purpose of the present study was to determine whether these two histological features were interrelated and to assess their relative influence on disease recurrence and survival following surgical resection. Archival tissue was retrieved from 55 patients who had undergone surgical resection for primary CRC and matching liver metastases. The nature of the invasive margin was determined by haematoxylin and eosin (H&E) histochemistry. Microvessel density was visualised using immunohistochemical detection of CD31 antigen and quantified using image capture computer software. Clinical details and outcome data were retrieved by case note review and collated with invasive margin and MVD data in a statistical database. Primary CRCs with a pushing margin tended to form capsulated liver metastases (P<0.001) and had a significantly better disease-free survival than the infiltrative margin tumours (log rank P=0.01). Primary cancers with a high MVD tended to form high MVD liver metastases (P=0.007). Microvessel density was a significant predictor of disease recurrence in primary CRCs (P=0.006), but not liver metastases. These results suggest that primary CRCs and their liver metastases show common histological features. This may reflect common mechanisms underlying the tumour-host interaction. PMID- 17353921 TI - Targeting homeostatic mechanisms of endoplasmic reticulum stress to increase susceptibility of cancer cells to fenretinide-induced apoptosis: the role of stress proteins ERdj5 and ERp57. AB - Endoplasmic reticulum (ER) malfunction, leading to ER stress, can be a consequence of genome instability and hypoxic tissue environments. Cancer cells survive by acquiring or enhancing survival mechanisms to counter the effects of ER stress and these homeostatic responses may be new therapeutic targets. Understanding the links between ER stress and apoptosis may be approached using drugs specifically to target ER stress responses in cancer cells. The retinoid analogue fenretinide [N-(4-hydroxyphenyl) retinamide] is a new cancer preventive and chemotherapeutic drug, that induces apoptosis of some cancer cell types via oxidative stress, accompanied by induction of an ER stress-related transcription factor, GADD153. The aim of this study was to test the hypothesis that fenretinide induces ER stress in neuroectodermal tumour cells, and to elucidate the role of ER stress responses in fenretinide-induced apoptosis. The ER stress genes ERdj5, ERp57, GRP78, calreticulin and calnexin were induced in neuroectodermal tumour cells by fenretinide. In contrast to the apoptosis inducing chemotherapeutic drugs vincristine and temozolomide, fenretinide induced the phosphorylation of eIF2alpha, expression of ATF4 and splicing of XBP-1 mRNA, events that define ER stress. In these respects, fenretinide displayed properties similar to the ER stress inducer thapsigargin. ER stress responses were inhibited by antioxidant treatment. Knockdown of ERp57 or ERdj5 by RNA interference in these cells increased the apoptotic response to fenretinide. These data suggest that downregulating homeostatic ER stress responses may enhance apoptosis induced by oxidative stress-inducing drugs acting through the ER stress pathway. Therefore, ER-resident proteins such as ERdj5 and ERp57 may represent novel chemotherapeutic targets. PMID- 17353922 TI - Telomere and telomerase in stem cells. AB - Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, and cellular replication causes their loss. In somatic cells, the activity of telomerase, a reverse transcriptase that can elongate telomeric repeats, is usually diminished after birth so that the telomere length is gradually shortened with cell divisions, and triggers cellular senescence. In embryonic stem cells, telomerase is activated and maintains telomere length and cellular immortality; however, the level of telomerase activity is low or absent in the majority of stem cells regardless of their proliferative capacity. Thus, even in stem cells, except for embryonal stem cells and cancer stem cells, telomere shortening occurs during replicative ageing, possibly at a slower rate than that in normal somatic cells. Recently, the importance of telomere maintenance in human stem cells has been highlighted by studies on dyskeratosis congenital, which is a genetic disorder in the human telomerase component. The regulation of telomere length and telomerase activity is a complex and dynamic process that is tightly linked to cell cycle regulation in human stem cells. Here we review the role of telomeres and telomerase in the function and capacity of the human stem cells. PMID- 17353923 TI - Safe liver resection following chemotherapy for colorectal metastases is a matter of timing. AB - Neoadjuvant chemotherapy (NC) can improve the resectability of hepatic colorectal metastases (CRM). However, there is concern regarding its impact on operative risk. We reviewed 750 consecutive liver resections performed for CRM in a single unit (1996-2005) to evaluate whether NC affected morbidity and mortality. Redo hepatic resections or patients receiving adjuvant chemotherapy following primary resection were excluded. A total of 245 resections were performed in patients not requiring NC (control group) (mean age 63, 67% male) and 252 in patients who had NC (mean age 62, 67% male). The mean (s.d.) duration of surgery was less in the control group (241(64) vs 255(64)min, P=0.014) as was the mean blood loss (390(264) vs 449(424)ml, P=0.069). Postoperative mortality (2 vs 2%) and morbidity (27 vs 29%, P=0.34) was similar between groups. More NC patients developed septic (2.4%) or respiratory (10.3%) complications compared to controls (0 and 5.3%, P<0.03), with significantly more surgical complications if the interval between stopping NC and undergoing surgery was or=35 hours) workers. Work characteristics (ie, job demands, decision latitude, and job variety), age, and gender were treated as covariates. RESULTS: No significant relationship between overtime and fatigue was found for any of the contract-hour groups. For the part-time workers, overtime was not related to higher work motivation, whereas for full-time workers it was. CONCLUSIONS: It is important to distinguish between overtime and long workhours, given the differential overtime-motivation relationship among part-time and full-time workers. This finding suggests that part-time employees work overtime for reasons other than motivation or that working overtime does not enhance work motivation for this group of employees. Overtime work seems to have a different meaning for part-time and full-time workers. PMID- 17353964 TI - Effect of shift work on body mass index and metabolic parameters. AB - OBJECTIVES: The aim of this cohort study was to investigate the effects of shift work on changes in parameters related to metabolic disturbances. METHODS: The study population included 1529 male blue-collar workers, aged 19-49 years at baseline, working in a sash and zipper factory in Japan. The participants were divided into four groups according to the work schedule at baseline, the end point being workers doing fixed daytime work in both years (day-day), workers who changed from shift work to fixed daytime work (shift-day), workers who changed from fixed daytime work to shift work (day-shift), and workers doing shift work in both years (shift-shift). The changes in body mass index (BMI), blood pressure, serum cholesterol, and glycosylated hemoglobin A1c over a period of 10 years were compared among the groups by work schedule. RESULTS: The age-adjusted mean increase in BMI was 1.03 kg/m(2) for the day-shift workers, and it was significantly larger than that of the day-day workers and shift-day workers. The shift-shift workers showed a significantly larger increase in BMI than the day day workers. These tendencies remained after adjustment for age and all other confounding factors, such as BMI, smoking, drinking, and leisure-time physical activity at baseline. The increase in total cholesterol tended to be higher among the shift-shift workers and the day-shift workers, but there were no significant differences. Blood pressure and hemoglobin A1c did not differ among the four groups. CONCLUSIONS: Shift work is considered to be a risk factor for excess weight. However, no significant difference in the biomarkers was found between daytime workers and shift workers. PMID- 17353965 TI - Simulator driving performance, subjective sleepiness and salivary cortisol in a fast-forward versus a slow-backward rotating shift system. AB - OBJECTIVES: The objectives of this study were to examine simulator driving and subjective sleepiness after morning, afternoon, and night shifts and to compare these differences, as well as objective stress, between a fast-forward and a slow backward rotating shift system. METHODS: The participants were male volunteers working in a chemical plant, 18 in a slow-backward rotating system and 18 in a fast-forward rotating system. All of the participants performed a driving simulator test and subjectively estimated sleepiness after a night, afternoon, and morning shift. Salivary cortisol samples, as indicators of the objective stress level, at the beginning of the workweek-after the second morning shift were compared between the two rotating shift systems. RESULTS: Lane drifting was higher after a night shift than after an afternoon shift. No effect of rotation system on driving performance could be shown. The subjective sleepiness scores were significantly higher in the slow-backward rotating group than in the fast forward rotating group. A significant effect of shift type was also observed, with lower levels of sleepiness after the afternoon shift than after the morning and night shifts. Salivary cortisol samples taken at the start of the workweek did not significantly differ between the fast-forward and the slow-backward rotation shift systems. CONCLUSIONS: This study indicated that shift type is more important than shift schedule-direction and speed of rotation-in determining driving performance. Performance seemed to be threatened mostly by a night shift and the least by an afternoon shift. In contrast, subjective sleepiness also differed between rotation groups and indicated an advantage of the fast-forward rotation system. The exploratory salivary cortisol measurements suggested that the shift systems studied do not differ in the level of stress they induce, that is to say at the beginning of the workweek. PMID- 17353966 TI - Validity of Nordic-style questionnaires in the surveillance of upper-limb work related musculoskeletal disorders. AB - OBJECTIVES: The study aimed at comparing results of standardized Nordic-style questionnaires with those of clinical examinations in two surveys on upper-limb work-related musculoskeletal disorders. METHODS: The "repetitive task" survey (1757 workers in 1993-1994 and 598 workers in 1996-1997) studied risk factors of the disorders among those exposed to repetitive work. The "Pays de la Loire" survey (2685 workers in 2002-2003) was part of a population-wide surveillance system. In both surveys, each worker completed a Nordic-style questionnaire and underwent a standardized clinical examination. The presence of at least one upper limb work-related musculoskeletal disorder was compared, with an evaluation of sensitivity, specificity, and kappa values, with a clinical examination as reference. In the second survey, a global score of a numerical scale for the severity of symptoms at the time of the examination was evaluated in the same way (plus ROC curves). RESULTS: Agreement between the questionnaire and the examination differed in the two surveys, from kappa 0.22 [95% confidence interval (95% CI) 0.19-0.23] in the "Pays de la Loire" survey to kappa 0.77 (95% CI 0.74 0.80) in the "repetitive task" survey in 1993-1994. Overall, sensitivity was excellent (82.3-100%). The specificity varied, from 51.1% in the "Pays de la Loire" survey to 82.4% for the >or=2 score based on the severity of symptoms in the survey. CONCLUSIONS: Nordic-style questionnaires exploring symptoms in the past year can be useful tools for monitoring upper-limb work-related musculoskeletal disorders, especially if they include numerical rating scales of symptom severity. Physical examination remains essential for a medical or clinical diagnosis. PMID- 17353968 TI - Occupational asthma and rhinitis in workers from a lasamide production line. AB - OBJECTIVES: A wide range of low-molecular-weight agents can cause occupational asthma. The chemical industry is an environment in which numerous hazardous substances are used. Lasamide (2,4-dichloro-5-sulfamoylbenzoic acid) is one of them (along with its precursors). METHODS: Five patients from a lasamide production line with suspected occupational asthma and rhinitis were examined. During the first visit, skin prick tests, total immunoglobulin E (IgE), a nonspecific bronchoprovocation test, and specific bronchoprovocation tests using occupational agents were performed to confirm the diagnosis of allergic diseases. During the follow-up visit (1-3 years after removal from exposure), all of the tests (except the specific bronchoprovocation test) were performed again. RESULTS: At the first hospitalization, the total IgE levels were increased in three patients. In addition, skin prick tests and the nonspecific bronchoprovocation test were positive for three patients. After the specific bronchoprovocation test, serious bronchoconstriction occurred in three patients; symptoms of rhinitis were present in all five patients. Several years after removal from exposure to the occupational agents, normalization (with respect to the parameters followed) was not yet complete for all of the patients. CONCLUSIONS: The process of lasamide production seems to be hazardous and is likely to cause allergic respiratory disease. The prognosis of allergic diseases caused by these products is not very favorable. Allergic symptoms (despite the removal from occupational allergen exposure) persisted even after several years. PMID- 17353967 TI - Cancer risk among 43000 Norwegian nurses. AB - OBJECTIVES: This study evaluated the influence of occupational exposure on cancer risk among female Norwegian nurses. METHODS: A historical prospective cohort study was performed. The cohort was established from the Norwegian Board of Health's registry of nurses and included women who graduated from a nursing school before 1985. The cohort (N=43 316) was linked to the Cancer Registry of Norway. The observed number of cases was compared with the expected number on the basis of national rates. Time since first employment, period of first employment, and duration of employment were used as indicators of exposure. Poisson regression analyses were used for internal comparisons, adjusting for age, period, and fertility. RESULTS: The nurses were followed over 1473931 person years. During the follow-up (1953-2002), 6193 cancer cases were observed. The standardized incidence ratio (SIR) for all cancers combined was close to unity. Significantly lower risks were found for cancers with a known association with alcohol and tobacco consumption and sexual activity. A significantly increased risk was found for breast cancer (SIR 1.14, 95% confidence interval (95% CI) 1.09 1.19), ovarian cancer (SIR 1.14, 95% CI 1.04-1.25), malignant melanoma (SIR 1.15, 95% CI 1.04-1.28), and borderline significant risk appeared for other skin cancer (SIR 1.12, 95% CI 0.98-1.29). A positive trend for increasing time since first exposure was found for breast cancer and malignant melanoma. CONCLUSIONS: The results indicate an association between working as a nurse and an increased risk of breast cancer and malignant melanoma. Decreased risks, found for several cancers, indicate favorable lifestyle habits among nurses. PMID- 17353969 TI - Performance of gentamicin population kinetic parameters in Portuguese neonates. AB - AIM: To evaluate the performance of eight different sets of gentamicin populational pharmacokinetic parameters, regarding potential implementation in clinical pharmacokinetic software as prior information. METHODS: The study involved 49 patients of 31.3+/-4.1 weeks of gestational age (GA), receiving gentamicin, and for whom peak and trough concentrations were obtained. Accuracy and precision were assessed by mean prediction error (ME), mean squared prediction error (MSE) and root mean squared prediction error (RMSE). Weighted prediction-error analysis was carried out in order to evaluate peak and trough concentrations together (ME(w), MSE(w) and RMSE(w)). RESULTS: The analysis showed CL=0.036 l/h/kg (< 34 weeks GA) or CL=0.051 l/h/kg (> or = 34 weeks GA), and V ( d )=0.5 l/kg (< or = 37 weeks GA) or Vd = 0.4 l/kg (>37 weeks of GA) as the most accurate and precise set of pharmacokinetic parameters (Set 4), presenting the highest percentage of clinically acceptable estimates (Error(Peak)<1 microg/ml, and Error(Trough) <0.375 microg/ml). CONCLUSION: The adoption of the previously mentioned set of parameters as population estimates seems to be the best option, bearing in mind the obtained results. However, we strongly believe that pharmacokinetic parameter determination of gentamicin should be carried out whenever possible in order to improve the rationale and cost-effectiveness of therapy. PMID- 17353970 TI - Prevalence of inappropriate prescribing in primary care. AB - OBJECTIVE: To describe the prevalence of inappropriate prescribing in primary care in Copenhagen County, according to the Medication Appropriateness Index (MAI) and to identify the therapeutic areas most commonly involved. SETTING: A cross-sectional study was conducted among 212 elderly ( >65 years) polypharmacy patients (five or more different medications) listed to 41 general practitioners (GPs) in the County of Copenhagen. METHOD: Patients exposed to polypharmacy were identified via the database recording the drug subsidy system of Danish pharmacies. For each patient, data were collected on subsidised medications prescribed over 3 months by the patients' own GPs. The GPs were asked to provide baseline information regarding the patients' medical history and detailed information regarding the subsidised and non-subsidised medications prescribed to the patients. A MAI was scored for medication prescribed to the patients. Topical, dermatological medications and medications not used regularly were excluded. RESULTS: 212 patients were prescribed 1621 medications by their GPs at baseline. In all, 640 (39.5%) of the medications had one or more inappropriate ratings in the 10 criteria making up the MAI. The main part of the patients (94.3%) had one or more inappropriate ratings among their medications. A total of 12.3% of the medications were rated as 'not indicated', 6% were rated as 'ineffective', 6.7% were given in an incorrect dose, 0.7% were prescribed with incorrect directions, 1.3% had impractical directions, 0.7% of the drugs had clinically significant drug-drug interactions, 8.6% had clinically significant drug-disease/condition interactions, 3.1% were unnecessary duplications, 16.5% were given in an unacceptable duration and 27.1% of the medications were not the least expensive alternative. The therapeutic groups most commonly involved in inappropriate prescribing were medications for treatment of peptic ulcer, cardiovascular medications, anti-inflammatory medications, antidepressants, hypnotics and anti-asthmatics. CONCLUSION: The overall prescribing quality in primary care in Copenhagen County, Denmark is good. However, the majority of patients used one or more medications with inappropriate ratings. The inappropriate prescribing relates to specific therapeutic groups and criteria, which should be targeted in future interventions. PMID- 17353971 TI - Infection risk related to the use of medicinal leeches. AB - OBJECTIVE: To assess the incidence of postoperative wound infections related to treatment with medicinal leeches at Ghent University Hospital. METHOD: A 2-year retrospective analysis of bacteriologic culture results of soft tissue infections in patients treated with medicinal leeches. RESULTS: Cultures of suspected wound infections were taken and susceptibility testing of isolates was performed on 17 of 47 patients (36.2%). Aeromonas was frequently isolated (18.5%). CONCLUSIONS: A high incidence of infection during and after application of medicinal leeches, despite their external decontamination, necessitates an antibiotic prophylaxis. In particular Aeromonas must be covered, as soft tissue infections with these bacteria can give serious complications. The prophylactic antibiotic should cover the most frequent isolated species taking into account the importance of Aeromonas and the susceptibility pattern. Based on the results, fluoroquinolones seem to be a good choice. The authors believe that practical recommendations to hospital pharmacists on prophylaxis during Hirudo medicinalis treatment, might enhance the safety of it's use by reducing the number of infections. PMID- 17353972 TI - Studies on chlorophyll biosynthesis and other things. AB - Our research on chlorophyll biosynthesis, over a period of approximately twenty years, has been described, emphasizing those areas in which our laboratory made significant and timely contributions. References to some of our most important articles are included. Portions of the chlorophyll biosynthetic pathway, in which our own laboratory was not involved, for example, the reduction of protochlorophyllide to chlorophyllide and the phytylation of the latter to yield chlorophyll a, have not been covered in this article. Those events which preceded my involvement with chlorophyll biosynthesis, but which contributed to the formation of my own scientific personality, are mentioned briefly in the Introduction. My non-scientific avocations have been included at the request of the reviewers and Govindjee. PMID- 17353973 TI - Joint composite-rotation adiabatic-sweep isotope filtration. AB - Joint composite-rotation adiabatic-sweep isotope filters are derived by combining the composite-rotation [Stuart AC et al. (1999) J Am Chem Soc 121: 5346-5347] and adiabatic-sweep [Zwahlen C et al. (1997) J Am Chem Soc 119:6711-6721; Kupce E, Freeman R (1997) J Magn Reson 127:36-48] approaches. The joint isotope filters have improved broadband filtration performance, even for extreme values of the one-bond (1)H-(13)C scalar coupling constants in proteins and RNA molecules. An average Hamiltonian analysis is used to describe evolution of the heteronuclear scalar coupling interaction during the adiabatic sweeps within the isotope filter sequences. The new isotope filter elements permit improved selective detection of NMR resonance signals originating from (1)H spins attached to an unlabeled natural abundance component of a complex in which the other components are labeled with (13)C and (15)N isotopes. PMID- 17353975 TI - Effect of iloprost on impaired anastomotic healing caused by 5-fluorouracil plus leucovorin. AB - PURPOSE: This experimental study was designed to investigate whether iloprost can reverse impaired colonic healing caused by immediate postoperative intraperitoneal administration of 5-fluorouracil plus leucovorin. METHODS: Eighty Wistar rats were randomized into four groups. After resection of a 1-cm segment of transverse colon, an end-to-end sutured anastomosis was generated. Rats received saline solution (Group 1), 5-fluorouracil plus leucovorin (Group 2), iloprost (Group 3), and 5-fluorouracil plus leucovorin plus iloprost (Group 4) intraperitoneally from the day of operation and once daily until killing. Each group was further randomized into two subgroups. Subjects were killed on the fifth (Subgroup a) and eighth (Subgroup b) postoperative days. After killing, anastomoses were examined macroscopically and graded histologically. Rats were measured for anastomotic bursting pressures and tissue hydroxyproline levels. RESULTS: The leakage rate of the anastomoses was significantly higher in the 5 fluorouracil plus leucovorin group compared with the other groups (P = 0.049). Bursting pressure was significantly lower in 2a subgroup (5-fluorouracil plus leucovorin, postoperative Day 5) than in 4a (5-fluorouracil plus leucovorin plus iloprost, postoperative Day 5; P < 0.001). Adhesion formation was significantly higher in all b subgroups compared with the Control b subgroup. Neoangiogenesis was significantly higher in iloprost and iloprost plus 5-fluorouracil plus leucovorin subgroups compared with the 5-fluorouracil plus leucovorin subgroups. Hydroxyproline levels, collagen deposition, fibroblasts, and white cell count were significantly higher in the iloprost plus 5-fluorouracil plus leucovorin b subgroup (postoperative Day 8) compared with the 5-fluorouracil plus leucovorin b subgroup (postoperative Day 8). CONCLUSIONS: The immediate postoperative, intraperitoneal administration of iloprost counteracts and reverses the negative effects of 5-fluorouracil plus leucovorin chemotherapy and protects colonic healing in rats. PMID- 17353976 TI - Robotic intragastric surgery: a new surgical approach for the gastric lesion. AB - BACKGROUND: Intragastric surgery is accepted as a minimally invasive procedure for mucosal or submucosal lesions. Robotic surgery promises to extend the capabilities of the minimally invasive surgeon and many surgical specialties are applying this new technology. However, there is no report of robotic intragastric surgery. We describe the use of the da Vinci Surgical System for intraluminal mucosal resection of the stomach. METHODS: We developed our porcine intragastric surgery model using the Tuebingen MIS Trainer. We set a tentative lesion on the posterior wall near the esophagocardiac junction (ECJ) of the stomach and performed mucosal resection of the lesion using the da Vinci Surgical System. We also performed closure of the defect after mucosal resection and subsequent closure of the intentional gastric perforation. RESULTS: Using our porcine intragastric surgery model, we successfully performed mucosal resection of the tentative lesion. We also smoothly completed closure of the defect and closure of the perforation without any complications. The mean size of the mucosa was 6 cm and the mean duration of the procedure was only 12 min. CONCLUSIONS: The safety and efficacy of robotic intragastric surgery was preliminarily established in this study. However, further studies are needed to prove its practical feasibility in humans using the da Vinci Surgical System to make it an effective operation. PMID- 17353977 TI - Colonoscopy in the very elderly: a review of 157 cases. AB - BACKGROUND: Colonoscopy is currently the best diagnostic modality for evaluating colonic diseases but studies of its use in the very elderly are limited. METHODS: A single-institution review of all patients aged 85 years or older who underwent colonoscopy from June 2003 to June 2005 was performed. Parameters evaluated included indications for colonoscopy, findings, ability to perform a complete colonoscopy, and immediate and delayed (< or =21 days) complications. RESULTS: A total of 157 patients aged 85 years or older (median = 87, range = 85-99) underwent colonoscopy during the two-year period. The cecal intubation rate was 90%. Number of cancers detected/indications for colonoscopy include gross or occult bleeding per rectum, 3/51 (5.9%); abnormal physical exam, 1/2 (50%); abnormal abdominal computed tomography, 3/5 (60%); anemia, 1/25 (4.0%); screening, 0/14; previous history of colonic malignancy, 0/10; previous history of polyps, 0/21; change in bowel habits, 0/5; family history of colonic malignancy, 0/6; abdominal pain, 0/4; diarrhea, 0/6; fecal impaction, 0/2; unknown, 0/6. Immediate complications included hemorrhage at a polypectomy site in one patient that was controlled endoscopically, one episode of bradycardia, and one incident of atrial fibrillation. There were no delayed complications resulting from colonoscopy. CONCLUSIONS: Our data suggest that colonoscopy can be safely and successfully performed in the very elderly. In patients with symptoms or suggestive radiographic findings, cancer was detected in 4.0%-60% of cases. No cases of cancer were discovered in those patients who were asymptomatic. PMID- 17353978 TI - Robot-assisted versus conventional laparoscopic fundoplication: short-term outcome of a pilot randomized controlled trial. AB - BACKGROUND: Robotic technology represents the latest development in minimally invasive surgery. Nevertheless, robotic-assisted surgery seems to have specific disadvantages such as an increase in costs and prolongation of operative time. A general clinical implementation of the technique would only be justified if a relevant improvement in outcome could be demonstrated. This is also true for laparoscopic fundoplication. The present study was designed to compare robotic assisted (RALF) and conventional laparoscopic fundoplication (CLF) with the focus on operative time, costs und perioperative outcome. METHODS: Forty patients with gastro-esophageal reflux disease were randomized to either RALF by use of the daVinci Surgical System or CLF. Nissen fundoplication was the standard anti reflux procedure. Peri-operative data such as length of operative procedure, intra-and postoperative complications, length of hospital stay, overall costs and symptomatic short-term outcome were compared. RESULTS: The total operative time was shorter for RALF compared to CLF (88 vs. 102 min; p = 0.033) consisting of a longer set-up (23 vs. 20 min; p = 0.050) but a shorter effective operative time (65 vs. 82 min; p = 0.006). Intraoperative complications included one pneumothorax and two technical problems in the RALF group and two bleedings in the CLF group. There were no conversions to an open approach. Mean length of hospital stay (2.8 vs. 3.3 days; p = 0.086) and symptomatic outcome thirty days postoperatively (10% vs. 15% with ongoing PPI therapy; p = 1.0 and 25% vs. 20% with persisting mild dysphagia; p = 1.0) was similar in both groups. Costs were higher for RALF than for CLF (3244 euros vs. 2743 euros, p = 0.003). CONCLUSION: In comparison with CLF, operative time can be shorter for RALF if performed by an experienced team. However, costs are higher and short-term outcome is similar. Thus, RALF can not be favoured over CLF regarding perioperative outcome. PMID- 17353979 TI - Experimental evaluation of the mechanical strength of stapling techniques. AB - BACKGROUND: The single stapling technique (SST) and the double stapling technique (DST) are common anastomoses for rectal cancer. Although many mechanical devices have been developed, the best choice remains unclear. In this study we examined the strength of anastomoses by determining their bursting pressures using an animal model. METHODS: The intestines of pigs were used. In experiment 1, we compared the bursting pressures for Endo GIA 60 blue, Endo GIA 60 green, and GIA 60 blue. In experiment 2, the bursting pressures of a buttressed cutting site and a nonbuttressed cutting site were measured. In experiment 3, the SST, DST, and DST with buttress using PCEEA were performed and the bursting pressures and points of these anastomoses were examined. RESULTS: The bursting pressure of Endo GIA 60 blue (80.3 +/- 10.5 mmHg) was significantly higher than that of Endo GIA 60 green (37.3 +/- 4.2 mmHg) and GIA 60 blue (31.7 +/- 5.8 mmHg) (p < 0.01). When a cut end was buttressed, the bursting pressure (149.6 +/- 37.6 mmHg) was significantly higher than that of the nonbuttressed end (75.3 +/- 25.1 mmHg) (p < 0.01). The bursting pressure among SST, DST, and DST with buttress was not significantly different. Only one bursting point was the crossing point of the PCEEA and Endo GIA and the bursting pressure of this point was much lower than that of the others. CONCLUSION: Endo GIA was most suitable for DST. The SST, DST, and DST with buttress had almost the same strength. The crossing point of PCEEA and Endo GIA may be a dangerous point for DST. PMID- 17353980 TI - The prevalence of sexual behavior disorders in patients with treated and untreated gastroesophageal reflux disease. AB - BACKGROUND: Gastroesophageal reflux disease (GERD) is a chronic disease. Sexual behavior is often altered in chronic illness. The aim of this study was to evaluate sexual behavior in patients affected with GERD before and after medical or surgical treatment in comparison to healthy controls (HC). METHODS: Upper GI endoscopy and 24-h ambulatory pH testing were performed to confirm GERD in symptomatic patients. GERD patients completed an anonymous questionnaire on sexual life before and after medical or surgical treatment. RESULTS: Compared with HC, untreated patients with GERD showed more frequent difficulty in attaining orgasm and painful intercourse. GERD patients after surgical treatment had significantly more difficulty in attaining orgasm, while after continuous medical treatment GERD patients compared with HC had significantly more difficulty in attaining orgasm, higher painful intercourse, lower sexual desire, and perceived more frequently that the partner was unhelpful. When compared with untreated conditions, GERD patients after surgical treatment had a significant improvement in attaining orgasm and in painful intercourse but a significant decrease in sexual desire, a lower satisfaction with their sexual life, and a higher prevalence of an unhelpful partner, whereas GERD patients after medical treatment had a decrease in all indices of sexual behavior. CONCLUSION: Untreated GERD is associated with disorders in sexual behavior. Compared with HC, only the surgical group partially improved after treatment. PMID- 17353981 TI - Anatomical redistribution of sweating after T2-T3 thoracoscopic sympathicolysis: a study of 210 patients. AB - BACKGROUND: The cutaneous influence areas of the different sympathetic ganglia have not been fully established to date. The aim of this study was to define the cutaneous influence area of sympathetic ganglia T2-T3. METHODS: A total of 210 patients with primary hyperhidrosis (PH) underwent 420 thoracoscopic sympathicolysis procedures of ganglia T2-T3 in a prospective study. All completed a preoperative questionnaire and a second questionnaire 12 months after the operation. The questionnaires evaluated perspiration in the different body areas. Only the zones of anhidrosis were considered in delimiting the cutaneous expression of sympathetic ganglia T2-T3. RESULTS: Redistribution of perspiration as reported by the patients comprised significant reduction in the palms, axillas, and soles, and an increase in the abdomen, back, and gluteal and popliteal regions. Regarding the incidence of anhidrosis by anatomical location, statistically significant changes were recorded in the head, hands, axillas, and soles (p < 0.001). CONCLUSIONS: Bilateral upper thoracic sympathicolysis is followed by redistribution of body perspiration, with a clear decrease in the zones regulated by mental or emotional stimuli, and an increase in the areas regulated by environmental stimuli, though we are unable to establish the etiology of this redistribution. PMID- 17353982 TI - Are energy sources required in laparoscopic cholecystectomy? Or should they be standby? PMID- 17353983 TI - Influence of complications and extent of weight loss on quality of life after laparoscopic Roux-en-Y gastric bypass. AB - INTRODUCTION: Obesity decreases health-related quality of life, but bariatric surgery improves it. This study evaluates the effect of laparoscopic Roux-en-Y gastric bypass, postoperative complications, and percentage of excess body weight loss on quality of life. METHODS: SF-36v.1 questionnaires were administered preoperative (n = 505), 1 year (n = 237) and 2 years (n = 106) following laparoscopic Roux-en-Y gastric bypass. Analysis was performed using Student's t test and multiple logistic regression analysis. Complications were defined as requiring additional intervention or hospitalization. SF-36 responses were normalized to 1998 US norms. RESULTS: Bariatric patients scored significantly lower on all scales compared to the normal population. Health-related quality of life notably improves after surgery. At 1 year, scores not only improved from baseline, but were higher than those of the non-obese reference population regardless of complications. Compared to patients at 2 years without complications, patients experiencing complications reported decreased scores, but scores remained higher than preoperative scores in five scales. At 1 and 2 years, < or = 50% excess body weight loss decreased scores; however, scores were significantly improved from baseline. CONCLUSIONS: Health-related quality of life in bariatric patients is worse than in controls, but it improves 1 and 2 years after laparoscopic Roux-en-Y gastric bypass. Complications or < or = 50% excess body weight loss slightly decreases this improvement. PMID- 17353984 TI - Robot-assisted laparoscopic mesh repair of incisional hernias with exclusive intracorporeal suturing: a pilot study. AB - BACKGROUND: The da Vinci robot laparoscopic incisional hernia repair with intracorporeal suturing may offer an alternative to transabdominal sutures and tackers. METHODS: From 2003 to 2005, 11 patients (median age, 71 years; median body mass index [BMI], 28) with small and medium-sized incisional hernias (median fascial defect, 19.6 cm2) were treated with the da Vinci robot system using intracorporeal mesh fixation with interrupted sutures. This pilot study aimed to assess the feasibility and report the morbidity with special reference to postoperative pain and long-term recurrence. RESULTS: The median operative time was 180 min. There was no conversion to open or standard laparoscopy and no postoperative mortality. The overall morbidity rate was 27%. One patient underwent reoperation on postoperative day 3 for peritonitis secondary to small bowel injury. The median visual analog pain score on postoperative day 1 was 3. Seven patients (63%) needed parenteral paracetamol until postoperative day 2. The median hospital stay was 3 days. During a median follow-up period of 25 months, no patient experienced recurrent hernia. One patient had a trocar-site herniation at 6 months. No patient experienced chronic suture site pain or discomfort. CONCLUSION: This is the first report of robot-assisted laparoscopic incisional hernia with exclusive intracorporeal suturing for mesh fixation in humans. The findings show that this technique is feasible and may not be associated with chronic postoperative pain. Further evaluation is needed to assess the benefit to the patient, but this investigation may be the basis for a future, prospective, randomized study. PMID- 17353985 TI - Laparoscopic parastomal hernia repair is feasible and safe: early results of a prospective clinical study including 55 consecutive patients. AB - BACKGROUND: Parastomal herniation is a common complication, and its operative treatment is notoriously difficult. Recently, the authors have described a laparoscopic technique for closure and reinforcement of the hernia with a hand made "funnel-shaped" Gore-Tex Dual Mesh. Potentially this technique combines the advantages of a mesh repair with those of minimal invasive surgery. METHODS: In 2002, a multicenter trial of this new technique was started in The Netherlands. To date, 55 consecutive patients (27 men; median age, 63 years) with a symptomatic primary (n = 45) or recurrent (n = 10) parastomal hernia have undergone elective surgery using this technique. The demographic, perioperative, and early follow-up data prospectively collected for these patients are presented in this report. RESULTS: Of the 55 procedures, 47 (85.5%) could be completed laparoscopically (median operation time, 120 min). Conversion to laparotomy was indicated because of dense adhesions prohibiting safe dissection (n = 4) or bowel injury (n = 4). No in-hospital mortality occurred. Postoperative recovery was uneventful for 47 patients (85%), who had a median hospital stay of 4 days. Surgical and nonsurgical complications occurred, respectively, for four patients each (7.2%). Full-thickness enterotomy appeared to be the most troublesome complication. After 6 weeks, when all the patients were reexamined, one recurrence was noted. CONCLUSION: Maximal efforts should be undertaken to prevent perioperative full-thickness enterotomy. Because this was achieved for the vast majority of patients, it is concluded that laparoscopic parastomal hernia repair is feasible and safe. Although a longer follow-up period is needed for definitive conclusions to be drawn regarding the recurrence rate, early follow-up evaluation shows very promising results. PMID- 17353986 TI - Increased cholecystectomy rate in the laparoscopic era: a study of the potential causative factors. PMID- 17353987 TI - Securing the appendiceal stump with the Gea extracorporeal sliding knot during laparoscopic appendectomy is safe and economical. AB - BACKGROUND: Laparoscopic appendectomy (LA) has become very popular. One criticism of this approach is the high cost of the disposable equipment such as the linear stapler. An alternative would be suture ligation of the appendiceal base. To prove the safety of the Gea extracorporeal sliding knot (GESK) for closure of the stump after LA, a retrospective study was conducted. METHODS: For this study, 63 LA procedures performed by one surgeon using the Gea knot (group A) were reviewed and compared with 63 LA procedures performed by two other surgeons (group B) using the linear stapler. The GESK is created with 0-prolene in the manner already described. The main variable was the presence or absence of blowout, leak, or fistula from the appendiceal stump. The secondary variables were abdominal abscess, wound infection, and need for readmission or reoperation. The results were analyzed using the appropriate statistical methods. RESULTS: Both groups were similar in terms of age, gender, and pathologic diagnosis. No patient in group A or B experienced a colonic fistula, stump blowout, or leak. In group A, one patient experienced interloop abscesses. There were two wound infections. In group B, one patient experienced a wound infection, and another patient had a wound dehiscence of the umbilical port, which required reoperation. No statistical differences were noted between the two groups. CONCLUSIONS: There are surgeons who routinely use sutures to secure the stump of the appendectomy. This study aimed to demonstrate that the GESK is as secure as the stapler for closure of the appendiceal stump. The GESK could be passed through a 5-mm trocar, potentially avoiding complications of a larger trocar site. The GESK seems to be an economic and safe alternative to the stapler. PMID- 17353988 TI - Robotic versus laparoscopic colectomy. AB - BACKGROUND: This study compared the experience and cost of the DaVinci Robotic system and laparoscopy for colon resections. METHODS: For this study, 30 consecutive robotic and 27 consecutive laparoscopic colectomies were divided into right and sigmoid colectomies for analysis. Comparisons included indications for surgery, gender, age, body mass index (BMI), estimated blood loss (EBL), length of operation, length of hospital stay (LOS), complications, operating room (OR) cost, OR personnel cost, OR supply cost, OR time cost, and total hospital cost. RESULTS: The comparison groups were similar in indications for surgery, gender, age, BMI, EBL, and LOS. The right colectomies included 17 robotic and 15 laparoscopic procedures. An intracorporeal anastomosis was performed in the robotic cases, and an extracorporeal anastomosis was performed in the laparoscopic cases. The total case time was 218.9 min for the robotic and 169.2 min for the laparoscopic procedures (p = 0.002). The total hospital cost was $9,255 for the robotic and $8,073 for the laparoscopic procedures (p = 0.430). The total OR cost was $5,823 for the robotic and $4,339 for the laparoscopic procedures (p < 0.000). The sigmoid colectomies included 13 robotic and 12 laparoscopic procedures. The robotic and laparoscopic cases were managed in similar sequence. The total case time was 225.2 min for the robotic and 199.4 min for the laparoscopic procedures (p = 0.128). The total hospital cost was $12,335 for the robotic and $10,697 for the laparoscopic procedures (p = 0.735). The total OR cost was $6,059 for the robotic and $4,974 for the laparoscopic procedures (p = 0.068). The complications in the robotic groups were more numerous, but were not attributable to equipment. CONCLUSIONS: The comparison groups were similar. The robotic cases were significantly longer for right colectomies because of the intracorporeal anastomosis instead of the extracorporeal anastomosis performed in the laparoscopy cases. Every cost category was higher for the robotic cases. The right colectomies showed significant increases in total OR cost, OR personnel cost, OR supply cost, and OR time cost. The sigmoid colectomies had significant increases in OR personnel cost and OR supply cost. The total hospital cost was higher for the robotic groups, but the difference was not statistically significant. PMID- 17353989 TI - Minilaparoscopic herniorrhaphy with hernia sac transection in children and young adults: a preliminary report. AB - BACKGROUND: We designed a technique of pure minilaparoscopic hernia sac transaction and ligation to repair primary inguinal hernias in children and young adults. METHODS: Between September 2003 and December 2004, 83 patients with primary inguinal hernia were treated surgically with minilaparoscopic herniorrhaphy. The mean patient age was 6.8 years. Before the operation there were synchronous bilateral hernias in 2 (2.4%) patients, left inguinal hernias in 39 (47%) patients, and right inguinal hernias in 42 (50.6%) patients. The minilaparoscopic herniorrhaphy was carried out with the 3-mm laparoscopic and hand instrument system. Three 3.5-mm trocar ports were used for the telescope and 3-mm instruments. The peritoneum overlying the internal ring was circumferentially incised, then the peritoneal defect was closed with intracorporeal sutures. RESULTS: One hundred and fourteen minilaparoscopic herniorrhaphies were performed. The mean followup period was 12.9 months. The mean operation time was 52 min. There was only one recurrence (1.2%) that was detected nine months after primary repair. All patients were able to return to unrestricted activity immediately and were discharged within 24 h after the operation. There was no reported case of testicular atrophy to date. CONCLUSIONS: Minilaparoscopic herniorrhaphy with hernia sac transaction is a safe and effective technique in children and young adults with indirect inguinal hernias. PMID- 17353990 TI - Phylogenetic analysis of the genus Petunia (Solanaceae) based on the sequence of the Hf1 gene. AB - Polymerase chain reaction fragment length polymorphisms and nucleotide sequences for a cytochrome P450 gene encoding flavonoid-3',5'-hydroxylase, Hf1, were studied in 19 natural taxa of Petunia. Natural Petunia taxa were classified into six groups based on major insertion or deletion events that occurred only in intron II of the locus. The maximum parsimony method was used to calculate strict consensus trees based on nucleotide sequences in selected regions of the Hf1 locus. Petunia taxa were divided into two major clades in the phylogenetic trees. Petunia axillaris (including three subspecies), P. exserta, and P. occidentalis formed a clade with 100% bootstrap support. This clade is associated with a consistently inflexed pedicel, self-compatibility in most taxa, and geographical distribution in southern and western portions of the genus range. The other clade, which comprised the remainder of the genus is, however, less supported (up to 71% bootstrap); it is characterized by a deflexed pedicel in the fruiting state (except P. inflata), self-incompatibility, and a northeastern distribution. A nuclear gene, Hf1, seems to be a useful molecular marker for elucidating the phylogeny of the genus Petunia when compared with the nucleotide sequence of trnK intron of chloroplast DNA. PMID- 17353991 TI - [FeFe] hydrogenases and their evolution: a genomic perspective. AB - Most hydrogenases (H2ases), the enzymes that produce or oxidize dihydrogen, possess dimetallic active sites and belong to either one of two phylogenetically distinct classes, the [NiFe] and the [FeFe] H2ases. These families of H2ases share a number of similarities regarding active site structure and reaction mechanism, as a result of convergent evolution. They are otherwise alien to each other, in particular with respect to protein sequence and structure, maturation mechanisms, and distribution among the realms of life. One of the interesting features of [FeFe] H2ases is their occurrence in anaerobic bacteria, anaerobic protists, and mitochondriate eukaryotes. They thus have the potential to report on important evolutionary events, including transitions from the prokaryote to the eukaryote lifestyle. Genome sequences yield a variety of [FeFe] H2ase sequences that have been implemented to shed light on the evolution of these proteins and their host organisms. PMID- 17353992 TI - The European hernia society groin hernia classification: simple and easy to remember. AB - After reviewing the available classifications for groin hernias, the European Hernia Society (EHS) proposes an easy and simple classification based on the Aachen classification. The EHS will promote the general and systematic use of this classification for intraoperative description of the type of hernia and to increase the comparison of results in the literature. PMID- 17353993 TI - Follicular lymphoma with extensive gastrointestinal tract involvement: follow-up by capsule endoscopy. AB - Follicular lymphoma with gastrointestinal tract involvement is rare. We describe the case of a young woman with follicular lymphoma with multiple nodular lesions involving segments of the proximal jejunum and terminal ileum. The presenting symptom was chronic diarrhea. The diagnosis was made by endoscopy with histologic examination of the mucosal lesions of the proximal and distal small intestine, immunohistochemical staining, and molecular analysis. The initial spread and pattern of the small bowel involvement, as well as treatment response, were evaluated by videocapsule endoscopy. The application of molecular analysis along with immunophenotypic evaluation has made it possible to precisely diagnose follicular lymphoma. In the present case, the use of capsule endoscopy improved the evaluation of the extent of small bowel involvement prior to and following treatment. PMID- 17353994 TI - Pretrial court diversion of people with mental illness. AB - Court diversion is a method of administering justice compassionately for persons with mental illness (PMI). Evidence-based practices of this intervention were identified by reviewing the existing literature. Findings suggest that: (a) formal case finding procedures are important for the early identification of mentally ill offenders in need of services, (b) stable housing enhances the possibility that the divertee will remain in regular contact with her or his treatment provider, and (c) active case management improves compliance and reduces the likelihood of recidivism. In summary, research has not yet yielded generalizable knowledge about diversion and thus, it is suggested that evaluations should involve well-defined indicators, benchmarks, and outcomes. PMID- 17353995 TI - Modifiable lifestyle factors affecting bone health using calcaneus quantitative ultrasound in adolescent girls. AB - One hundred and fourteen girls were measured for calcaneus QUS (stiffness index score), calcium intake, weight, and total hours spent in physical activity (moderate to high-impact activities and low to no-impact activities). Multiple regression analysis indicated that hours spent in moderate to high-impact activities, current calcium intake, and weight significantly predicted SI. INTRODUCTION: To determine the influence of modifiable lifestyle factors on adolescent girls' bone health measured by calcaneus quantitative ultrasound (QUS). METHODS: One hundred and fourteen girls, ages 14-18 (15.97 +/- .7), enrolled in high school physical education classes, were measured for calcaneus QUS (stiffness index score), height, weight, current calcium intake from 2-3 day food records, and estimated total hours spent in physical activity from kindergarten to present. Cumulative physical activity hours were separated into two classifications (according to their estimated strain from ground reaction force): moderate to high-impact activities and low to no-impact activities. RESULTS: Pearson correlations between stiffness index (SI) and age, height, weight, current calcium intake, and hours spent in moderate to high-impact versus low to no-impact activities indicated a positive relationships between SI and weight (r = .259, p = .005), current calcium intake (r = .286, p = .002), and hours spent in moderate to high-impact activities (r = .451, p < .001). Multiple regression between SI and the above independent variables indicated that collectively, hours spent in moderate to high-impact activities, current calcium intake, and weight (r (2) = .363, p = <.001) significantly predicted SI. CONCLUSION: Our data indicate that moderate to high-impact activities, current calcium intake, and weight positively influence bone properties of the calcaneus in adolescent girls. PMID- 17353996 TI - Silver nanoparticles: partial oxidation and antibacterial activities. AB - The physical and chemical properties of silver nanoparticles that are responsible for their antimicrobial activities have been studied with spherical silver nanoparticles (average diameter approximately 9 nm) synthesized by the borohydride reduction of Ag+ ions, in relation to their sensitivity to oxidation, activities towards silver-resistant bacteria, size-dependent activities, and dispersal in electrolytic solutions. Partially (surface) oxidized silver nanoparticles have antibacterial activities, but zero-valent nanoparticles do not. The levels of chemisorbed Ag+ that form on the particle's surface, as revealed by changes in the surface plasmon resonance absorption during oxidation and reduction, correlate well with the observed antibacterial activities. Silver nanoparticles, like Ag+ in the form of AgNO3 solution, are tolerated by the bacteria strains resistant to Ag+. The antibacterial activities of silver nanoparticles are related to their size, with the smaller particles having higher activities on the basis of equivalent silver mass content. The silver nanoparticles aggregate in media with a high electrolyte content, resulting in a loss of antibacterial activities. However, complexation with albumin can stabilize the silver nanoparticles against aggregation, leading to a retention of the antibacterial activities. Taken together, the results show that the antibacterial activities of silver nanoparticles are dependent on chemisorbed Ag+, which is readily formed owing to extreme sensitivity to oxygen. The antibacterial activities of silver nanoparticles are dependent on optimally displayed oxidized surfaces, which are present in well-dispersed suspensions. PMID- 17353997 TI - Anatomic mapping and evaluation of the esophagus in relation to the cervical vertebral body. AB - The relationship of the esophagus to the cervical vertebral body (CVB), disc space and longus colli (LC) muscles, to our knowledge, has not been previously studied. The purpose of this study was to quantify the relationship of the esophagus to the CVB, disc space and LC. 30 patients were selected for a retrospective review of computed tomography (CT) scans. Measurements between the esophagus and the C5, C6, and C7 vertebral bodies as well as the C5/6 and C6/7 disc spaces were performed in the midline, 3 mm right and left of midline, and at the edge of the LC on both sides. The closest distance of the esophagus to the CVB and disc space occurs at the midline (range 1.02-1.31 mm at each level). The furthest distance occurred at the edge of the right LC (range 2.67-3.30 mm at each level). The mean distance from the edge of the right LC to the midline was significantly greater (P < 0.01) than mean distance from the edge of the left LC to the midline. No statistical significant differences were observed when comparing measurements at the individual vertebral bodies and disc spaces. The results of the study demonstrate that the esophagus lies in closest proximity to the CVB and disc space in the midline. A larger potential space exists between the esophagus and the CVB and disc space at the edge of the LC. These results may provide insight into a potential cause of post-operative dysphagia. Furthermore, it may help guide the future design of cervical plates to better utilize the potential space between the esophagus and the CVB and disc space at the edge of the LC. PMID- 17353998 TI - The Idd6.2 diabetes susceptibility region controls defective expression of the Lrmp gene in nonobese diabetic (NOD) mice. AB - The identification of genes mediating susceptibility to type 1 diabetes (T1D) remains a challenging task. Using a positional cloning approach based on the analysis of nonobese diabetic (NOD) mice congenic over the Idd6 diabetes susceptibility region, we found that the NOD allele at this locus mediates lower mRNA expression levels of the lymphoid restricted membrane protein gene (Lrmp/Jaw1). Analysis of thymic populations indicates that Lrmp is expressed mainly in immature thymocytes. The Lrmp gene encodes a type 1 transmembrane protein that localizes to the ER membrane and has homology to the inositol 1,4,5 triphosphate receptor-associated cGMP kinase substrate gene, which negatively regulates intracellular calcium levels. We hypothesize that the observed decrease in expression of the Lrmp gene in NOD mice may constitute a T1D susceptibility factor in the Idd6 region. PMID- 17353999 TI - [Typing for HLA matching. Advantages for keratoplasty]. AB - Matching of human leukocyte antigens of donors and recipients (HLA matching) plays a significant role in kidney, heart, lung, and stem cell transplantation. New data demonstrate that HLA matching also significantly prolongs the survival of corneal grafts. The reasons for the late recognition of the significance of HLA matching in corneal transplantation are on the one hand the immune privilege of the eye, which allows corneal transplantation under certain conditions without immunosuppressive therapy, and on the other hand highly erroneous serological typing. Recent molecular DNA typing is almost without errors, and the selection of grafts on the basis of results obtained using this method will improve the long-time survival of future corneal grafts. Today, there are several reasons arguing for the general practice of HLA matching in keratoplasty. PMID- 17354000 TI - A novel locus for distal motor neuron degeneration maps to chromosome 7q34-q36. AB - The motor neuron diseases (MND) are a group of related neurodegenerative diseases that cause the relative selective progressive death of motor neurons. These diseases range from slowly progressive forms including hereditary motor neuropathy (HMN), to the rapidly progressive disorder amyotrophic lateral sclerosis (ALS). There is clinical and genetic overlap among these MNDs, implicating shared pathogenic mechanisms. We recruited a large family with a MND that was previously described as juvenile ALS and distal HMN. We identified a novel MND/HMN locus on chromosome 7q34-q36 following a genome-wide scan for linkage in this family. The disease causing mutation maps to a 26.2 cM (12.3 Mb) interval flanked by D7S2513 and D7S637 on chromosome 7q34-q36. Recombinant haplotype analysis including unaffected individuals suggests that the refined candidate interval spans 14.3 cM (6.3 Mb) flanked by D7S2511 and D7S798. One gene in the candidate interval, CDK5, was selected for immediate mutation analysis based upon its known association with an ALS-like phenotype in mice however, no mutations were identified. Identification of genes causing familial MND will lead to a greater understanding of the biological basis of both familial and sporadic motor neuron degeneration including ALS. PMID- 17354001 TI - Gene symbol: ALMS1. PMID- 17354002 TI - Selective 3D ultrashort TE imaging: comparison of "dual-echo" acquisition and magnetization preparation for improving short-T 2 contrast. AB - OBJECTIVE: The objective of this study was to compare two different schemes for long-T (2) component suppression in ultrashort echo-time (UTE) imaging. The aim was to increase conspicuity of short-T (2) components accessible by the UTE technique. MATERIALS AND METHODS: A "dual-echo" and a magnetization-preparation approach for long-T (2) and fat suppression were implemented on clinical scanners. Both techniques were compared in 3D UTE exams on healthy volunteers regarding short-T (2) Signal-to-noise ratio (SNR), long-T (2) suppression quality, and scan efficiency. A quantitative SNR evaluation was performed using ankle scans of six volunteers. T (2) suppression profiles were simulated for both approaches to facilitate interpretation of the observations. RESULTS: At 1.5 T, both techniques perform equally well in suppressing long-T (2) components and fat. Magnetization preparation requires more shimming effort due to the use of narrow-band pulses, while the "dual-echo" technique requires a post-processing step to form a subtraction image. For scans with a short repetition time (TR), the "dual-echo" approach is much faster than the magnetization preparation, which depends on slow T (1) recovery between preparation steps. The SNR comparison shows slightly higher short-T (2) SNR for the "dual-echo" approach. At 3.0 T, magnetization preparation becomes more challenging due to stronger off-resonance effects. CONCLUSION: Both techniques are well suited for long-T (2) suppression and offer comparable short-T (2) SNR. However, the "dual-echo" approach has strong advantages in terms of scan efficiency and off-resonance behavior. PMID- 17354003 TI - [Laboratory diagnostics for systemic sclerosis]. AB - For systemic sclerosis, laboratory tests can play a supplementary role to clinical investigations, imaging techniques and functional tests. Typical autoantibodies support early diagnosis and help in assigning patients to subgroups of the disease; negative results for antinuclear antibodies suggest exclusion of the diagnosis. To detect organ involvement and comorbidity, the laboratory contributes by clinical chemistry, in certain cases by histopathological findings and by the cytological assessment of broncho-alveolar lavage fluid. Inflammatory parameters are of minor importance. Multiple autoantibody determinations in the course of the disease are not yet helpful. Numerous additional laboratory parameters are of value for investigating pathogenesis, but have not yet been generally introduced into the routine diagnostics of systemic sclerosis. PMID- 17354004 TI - When quantity trumps number: discrimination experiments in cotton-top tamarins (Saguinus oedipus) and common marmosets (Callithrix jacchus). AB - The capacity for non-linguistic, numerical discrimination has been well characterized in non-human animals, with recent studies providing careful controls for non-numerical confounds such as continuous extent, density, and quantity. More poorly understood are the conditions under which animals use numerical versus non-numerical quantification, and the nature of the relation between these two systems. Here we test whether cotton-top tamarins and common marmosets can discriminate between two quantities on the basis of the amount of food rather than on number. In three experiments, we show that when choosing between arrays containing different numbers and sizes of food objects, both species based their decisions on the amount of food with only minor influences of numerical information. Further, we find that subjects successfully discriminated between two quantities differing by a 2:3 or greater ratio, which is consistent with the ratio limits found for numerical discrimination with this species. These studies demonstrate that non-human primates possess mechanisms that enable quantification of total amount, in addition to the numerical representations demonstrated in previous studies, with both types of quantification subject to similar processing limits. PMID- 17354005 TI - Remodelling of the angular collagen fiber distribution in cardiovascular tissues. AB - Understanding collagen fiber remodelling is desired to optimize the mechanical conditioning protocols in tissue-engineering of load-bearing cardiovascular structures. Mathematical models offer strong possibilities to gain insight into the mechanisms and mechanical stimuli involved in these remodelling processes. In this study, a framework is proposed to investigate remodelling of angular collagen fiber distribution in cardiovascular tissues. A structurally based model for collagenous cardiovascular tissues is extended with remodelling laws for the collagen architecture, and the model is subsequently applied to the arterial wall and aortic valve. For the arterial wall, the model predicts the presence of two helically arranged families of collagen fibers. A branching, diverging hammock type fiber architecture is predicted for the aortic valve. It is expected that the proposed model may be of great potential for the design of improved tissue engineering protocols and may give further insight into the pathophysiology of cardiovascular diseases. PMID- 17354006 TI - Three-dimensional simulation of anisotropic cell-driven collagen gel compaction. AB - Tissue equivalents (TEs), formed by entrapping cells in a collagen gel, are an important model system for studying cell behavior. We have previously (Barocas and Tranquillo in J Biomech Eng 117:161-170, 1997a) developed an anisotropic biphasic theory of TE mechanics, which comprises five coupled partial differential equations describing interaction among cells and collagen fibers in the TE. The model equations, previously solved in one or two dimensions, were solved in three dimensions using an adaptive finite-element platform. The model was applied to three systems: a rectangular isometric cell traction assay, an otherwise- acellular gel containing two islands of cells, and an idealized tissue engineered cardiac valve leaflet. In the first two cases, published experimental data were available for comparison, and the model results were consistent with the experimental observations. Fibers and cells aligned in the fixed direction in the isometric assay, and a region of strong fiber alignment arose between the two cell islands. For the valve problem, the alignment predicted by the model was generally similar to that observed experimentally, but an asymmetry in the experiment was not captured by the model. PMID- 17354007 TI - Developmental environment, cultural transmission, and mate choice copying. AB - Using female mate choice copying as a rudimentary form of cultural transmission, this study provides evidence that social environment during development has a significant effect on the tendency to use culturally acquired information. Groups of newborn guppies (Poecilia reticulata) were raised for 35 days in 1 of 5 "developmental environments". Groups of 15 newborns were raised in pools with no adults (treatment 1), both adult male and female guppies (treatments 2 and 3), only adult females (treatment 4) or only adult males (treatment 5). Mature females raised in treatments 1 and 2, but not treatments 3, 4, and 5, copied the mate choice of others. Treatments 1 and 2 correspond to social structures that guppies experience during their development in the wild. Newborn guppies swim together in shoals (analogous to treatment 1). As they mature, juveniles join schools of adult males and females (analogous to treatments 2). At no time during the normal developmental process are juveniles found with males, but only unreceptive females (as was the case for long periods in treatment 3) or in the presence of adults of only one sex (analogous to treatments 4 and 5). As such, normal developmental environments prime guppies for cultural transmission, while unnatural environments fail to do so. PMID- 17354009 TI - Potential impact of ABCB1 (p-glycoprotein) polymorphisms on avermectin toxicity in humans. AB - Several members of the ATP binding cassette (ABC) transporter protein superfamily perform xenobiotic efflux functions in mammals, limiting gut absorption, mediating excretion, and controlling entry of a wide range of chemicals to sensitive compartments such as brain, testes and foetus. Perhaps the best characterised of these is p-glycoprotein (gene name ABCB1/MDR1), a barrier epithelia expressed protein with structurally diverse substrates, including the avermectin pesticides. In specific mouse and dog strains, ABCB1 mutations have been identified that result in loss of p-glycoprotein function in the blood brain barrier (BBB) and increased susceptibility to avermectin neurotoxicity. As yet no large rearrangements of the human ABCB1 gene analogous to those in the mouse and dog have been identified. However, numerous human ABCB1 single nucleotide polymorphisms (SNPs) have been identified, the allelic frequencies of which vary with ethnicity. There is no clear consensus on whether or not SNPs, or combinations of SNPs, reduce human p-glycoprotein functionality. However, recent in vivo human data indicate that the two commonest ABCB1 haplotypes both exhibit full BBB functionality. We discuss here the role of p-glycoprotein in limiting brain absorption of avermectin pesticides, as well as the potential impact of the reported functional effects and population frequencies of known ABCB1 polymorphisms on avermectin pesticide risk assessments. PMID- 17354008 TI - Triterpene saponin hemi-biosynthesis of a leaf beetle's (Platyphora kollari) defensive secretion. AB - The adults of the leaf beetle Platyphora kollari (Chrysomelidae) are able to metabolise the oleanane triterpene beta-amyrin (1) into the glycoside 3-O-beta-D: -glucopyranosyl-(1-->4)-beta-D: -glucuronopyranosyl-hederagenin (2) that is stored in their defensive glands. The aim of this study was to test the hypothesis that oleanolic acid (3) is an intermediate in the conversion of 1 into 2 and to check whether the sequestration of pentacyclic triterpenes is selective in favour of beta-amyrin (1). To this end, adults of P. kollari were fed with Ipomoea batatas leaf disks painted with a solution of [2,2,3-(2)H(3)]oleanolic acid or [2,2,3-(2)H(3)]alpha-amyrin and the secretion of their defensive glands analysed by HPLC-ESIMS. The data presented in this work indicated that the first step of the transformation of beta-amyrin (1) into the sequestered glycoside 2 is its oxidation into oleanolic acid (3) and that this conversion is selective but not specific in favour of beta-amyrin (1). PMID- 17354010 TI - A case of multiple skeletal lesions of brown tumors, mimicking carcinoma metastases. AB - Brown tumor is not a true tumor, being an unusual reactive lesion in association with primary or secondary hyperparathyroidism. We report a 23-year-old woman, who initially presented with lower back pain caused by ureterolithiasis. The initial diagnosis of brown tumor was delayed, but later pain in her leg worsened and a sacral lesion was incidentally discovered on lumbar magnetic resonance imaging (MRI); multiple destructive bone lesions were then found radiologically. The radiological features of the multiple bone lesions, which mimicked multiple metastatic tumors, seemed to be those of the terminal stage of malignancy. However, pathological examination and abnormal laboratory data showing elevated serum calcium, alkaline phosphatase, and parathyroid hormone and low serum phosphate confirmed the diagnosis of brown tumor. Adenoma in the parathyroid gland was confirmed and surgically resected. The clinical symptoms of bone pain, and abnormal radiological findings and laboratory data were resolved 6 months after surgery. Synthetic analysis of the clinical, radiological, and laboratory findings was necessary for the definite diagnosis of brown tumor. PMID- 17354011 TI - Long-term results of various therapy concepts in severe pilon fractures. AB - INTRODUCTION: Intra-articular fractures of the tibia plafond are among the most challenging of orthopaedic problems. This is a retrospective case-control study of surgically treated pilon fractures which was undertaken to compare the internal fixation with the two external fixation methods. METHODS: This is a case control study of 55 patients with 55 pilon fractures. There were 36 type C and 19 type B. Of these fractures, 24 were open and 31 closed. Three surgical protocols were used. In 20 patients, Group A, a half pin external fixator with ankle spanning was performed. The mean age of patients was 42.0 years (22.0-74.0), SD 14.1 and the mean follow-up was 77.7 months (38.0-132.0), SD 25.4. In 22 patients, Group B, a single ankle sparring ring hybrid external fixator under a small arthrotomy was performed. The mean age of patients was 48.4 years (28.0 76.0), SD 12.4 and mean follow-up was 67.9 months (36.0-132.0), SD 27.8. In 13 patients, Group C, a two-staged internal fixation was performed. The mean age was 45.6 years (30.0-66.0), SD 9.7 and the mean follow-up was 78.6 months (55.0 132.0), SD 25.4. We addressed the dissimilarity of the type of fracture in each group performing supplementary stratified analyses within each fracture type group. RESULTS: Group A had union in 6.9 months, group B in 5.6 months and group C in 5.1 months; P = 0.009. Six patients (Group A), two (Group B), and one (Group C) had limitation of ankle motion; P = 0.47. One patient from group C developed infection and the plate was removed. Four patients (Group A), one (Group B), and one (Group C) have developed posttraumatic arthritis (loss of joint space and pain); P = 0.25. Seven patients from Group A have reduced their activities; P = 0.004. In stratified statistical analysis by type of fracture, the associations noted for both fracture groups combined were also noted separately within each fracture group. CONCLUSION: In this long term follow-up study, the two-staged internal fixation and the hybrid fixation with small arthrotomy were equally efficacious in achieving bone union. Patients in external fixation with the ankle spanning had a significantly higher rate of delayed union. Also more patients in this group have reduced their activities. PMID- 17354012 TI - Antigen-antibody interaction from quartz crystal microbalance immunosensors based on magnetic CoFe2O4/SiO2 composite nanoparticle-functionalized biomimetic interface. AB - A new quartz crystal microbalance immunoassay for the detection of carcinoembryonic antigen (CEA) was developed by means of immobilizing anti-CEA onto magnetic CoFe2O4/SiO2 composite nanoparticles-functionalized biomimetic interface. Under optimal conditions, the frequency shift was proportional to the CEA concentration in the range of 2.5-55 ng/mL with a detection limit of 0.5 ng/mL at a signal-to-noise ratio of 3. Moreover, the immunosensor system showed an acceptable reproducibility and stability. Clinical serum specimens were assayed with this method, and the results were in acceptable agreement with those obtained from ELISA. Compared with the conventional ELISA assay, the proposed immunoassay system was simple and rapid without multiple labeling and separation steps. Importantly, the developed immunoassay protocol could be further extended for the determination of other antigens. PMID- 17354013 TI - Interaction energies in non-covalently bound intermolecular complexes derived using the subsystem formulation of density functional theory. AB - Interaction energies for a representative sample of 39 intermolecular complexes are calculated using two computational approaches based on the subsystem formulation of density functional theory introduced by Cortona (Phys. Rev. B 44:8454, 1991), adopted for studies of intermolecular complexes (Wesolowski and Weber in Chem. Phys. Lett. 248:71, 1996). The energy components (exchange correlation and non-additive kinetic) expressed as explicit density functionals are approximated by means of gradient-free- (local density approximation) of gradient-dependent- (generalized gradient approximation) approximations. The sample of the considered intermolecular complexes was used previously by Zhao and Truhlar to compare the interaction energies derived using various methods based on the Kohn-Sham equations with high-level quantum chemistry results considered as the reference. It stretches from rare gas dimers up to strong hydrogen bonds. Our results indicate that the subsystem-based methods provide an interesting alternative to that based on the Kohn-Sham equations. Local density approximation, which is the simplest approximation for the relevant density functionals and which does not rely on any empirical data, leads to a computational approach comparing favorably with more than twenty methods based on the Kohn-Sham equations including the ones, which use extensively empirical parameterizations. For various types of non-bonding interactions, the strengths and weaknesses of gradient-free and gradient-dependent approximations to exchange correlation and non-additive kinetic energy density functionals are discussed in detail. PMID- 17354014 TI - Oncological and functional results of open, robot-assisted and laparoscopic radical prostatectomy: does surgical approach and surgical experience matter? AB - The treatment of prostate cancer has undergone a fundamental change in the last decade. New surgical and nonsurgical minimal invasive methods have evolved. As the methodology of the different treatments is commonly known to urologists, this article focuses on oncological and functional outcome of open retropubic (ORP), trans- or extraperitoneal endoscopical (LRP), and robot-assisted radical prostatectomy (RALP), based on personal experience and review of the literature. A MEDLINE search was performed to review the literature on LRP and RALP between 1982 and 2007 with special emphasis on oncological and functional results, technical considerations, comparison of LRP and RALP to ORP, laparoscopic training, historical aspects, and cost-efficiency of the techniques. Based on diligent training and proctoring programs, a continuous dissemination of laparoscopic techniques takes place. There is a trend towards the extraperitoneal access in most of the minimal invasive programs at least in the European community. Mid-term outcomes of LRP and short-term outcomes of RALP achieved equivalence to open surgery with regards to complications, oncologic and functional results. Distinct advantages of LRP include less postoperative pain, lower transfusion rates, shorter convalescence, and better cosmetics. In contrast to RALP, LRP reaches cost-equivalence with open surgery in selected centers. LRP and RALP reproduce the short-term results of open surgery while providing the advantages of a minimal access. Video-assisted teaching improves the transfer of anatomical knowledge and technical knowhow, but the discussion about the longer learning curve for laparoscopy handling remains. The future will show if European centers adopt the use of robots comparable to the United States. PMID- 17354015 TI - O6-benzylguanine and BCNU in multiple myeloma: a phase II trial. AB - PURPOSE: Carmustine (BCNU) is known to have modest activity in multiple myeloma; however, resistance to BCNU manifests by the activity of O6-methylguanine methyltransferase (MGMT). The objective of this study was to determine the safety and efficacy of depletion of MGMT activity in plasma cells using O6-benzylguanine (O6-BG) with BCNU in patients with multiple myeloma. METHODS: Patients with previously treated or untreated multiple myeloma were eligible. Cycles of O6-BG at a dose of 120 mg/m2 and BCNU at a dose of 40 mg/m2 were repeated every 6 weeks. RESULTS: Seventeen patients were enrolled on the study, with a median follow-up of 24.5 (range 5-69) months. One complete response (7%) and 3 partial responses (20%) were observed. Nine patients (60%) had stable disease. Bone marrow studies demonstrated 94% depletion of MGMT activity in CD38+ marrow cells. The most frequent grade 3 and 4 adverse events were neutropenia (71%), lymphocytopenia (53%), and thrombocytopenia (53%). CONCLUSIONS: Chemotherapy utilizing the MGMT inhibitor O6-benzylguanine and BCNU results in inhibition of MGMT activity in malignant plasma cells and produces meaningful responses in a modest proportion of patients with multiple myeloma. Hematologic toxicity with this regimen is significant and dose-limiting. PMID- 17354016 TI - Persistence of direction increases the drift velocity of run and tumble chemotaxis. AB - Escherichia coli is a motile bacterium that moves up a chemoattractant gradient by performing a biased random walk composed of alternating runs and tumbles. Previous models of run and tumble chemotaxis neglect one or more features of the motion, namely (a) a cell cannot directly detect a chemoattractant gradient but rather makes temporal comparisons of chemoattractant concentration, (b) rather than being entirely random, tumbles exhibit persistence of direction, meaning that the new direction after a tumble is more likely to be in the forward hemisphere, and (c) rotational Brownian motion makes it impossible for an E. coli cell to swim in a straight line during a run. This paper presents an analytic calculation of the chemotactic drift velocity taking account of (a), (b) and (c), for weak chemotaxis. The analytic results are verified by Monte Carlo simulation. The results reveal a synergy between temporal comparisons and persistence that enhances the drift velocity, while rotational Brownian motion reduces the drift velocity. PMID- 17354017 TI - Prediction of small, noncoding RNAs in bacteria using heterogeneous data. AB - sRNAFinder is a new gene prediction system for systematic identification of noncoding genes in bacteria. Most noncoding RNAs in prokaryotes belong to a class of genes denoted as small RNAs (sRNAs). In the model organism Escherichia coli, over 70 sRNA genes have been identified, and the existence of many more has been hypothesized. While various sources of information have proven useful for prediction of novel sRNA genes, most computational approaches do not take advantage of the disparate sources of data available for identifying these noncoding RNA genes. We present a general probabilistic method for predicting sRNA genes in bacteria. The method, based on a general Markov model, is implemented in the computational tool sRNAFinder. sRNAFinder incorporates heterogeneous data sources for gene prediction, including primary sequence data, transcript expression data from microarray experiments, and conserved RNA structure information as determined from comparative genomics analysis. We demonstrate that sRNAFinder improves upon current tools for identifying small, noncoding genes in bacteria. PMID- 17354018 TI - Guggulsterone production in cell suspension cultures of the guggul tree, Commiphora wightii, grown in shake-flasks and bioreactors. AB - Cell suspension cultures of Commiphora wightii, grown in modified MS medium containing 2,4-dichlorophenoxyacetic acid (0.5 mg l(-1)) and kinetin (0.25 mg l( 1)), produced approximately 5 microg guggulsterone g(-1) dry wt. In a 2 l stirred tank bioreactor, the biomass was 5.5 g l(-1) and total guggulsterone was 36 microg l(-1). PMID- 17354019 TI - Interaction of ribonucleotides with metal hexacyanocobaltate(III): a possible role in chemical evolution. AB - It has been proposed that metal cyanide complexes would have acted as effective prebiotic catalysts. Insoluble metal cyanide complexes could have concentrated biomonomers from the dilute prebiotic soup, facilitating certain prebiotic reactions. In the light of the above hypothesis, interaction of four ribonucleotides, namely 5'-AMP, 5'-GMP, 5'-CMP, and 5'-UMP with copper(II)- and cadmium(II) hexacyanocobaltate(III) has been studied. The interaction was found to be maximum at neutral pH. 5'-GMP showed greater interaction with both the metal hexacyanocobaltate(III) while copper(II) hexacyanocobaltate(III) showed greater uptake than cadmium(II) hexacyanocobaltate(III) for all the four ribonucleotides studied. Infrared spectral studies of ribonucleotides, metal hexacyanocobaltate(III) and ribonucleotide - metal hexacyanocobaltate(III) adducts indicated that the nitrogen base and phosphate moiety of ribonucleotides interact with outer divalent metal ion present in the lattice of metal hexacyanocobaltate(III). PMID- 17354020 TI - QuiCk-IntraOperative Bio-Intact PTH assay at parathyroidectomy for secondary hyperparathyroidism. AB - BACKGROUND: In uremic patients, metabolism of 1-84 parathyroid hormone (PTH) and fragments are delayed, and in these patients, the usefulness of intraoperative PTH assay may be problematic. We evaluated the usefulness of the QuiCk IntraOperative Bio-Intact PTH (QPTH) assay for uremic patients with secondary hyperparathyroidism who required total parathyroidectomy (PTx) with forearm autograft. The purpose of our study was to recognize whether QPTH in uremic patients was useful to determine during operation whether complete PTx had been achieved. METHODS: Forty-four patients who underwent initial PTx were enrolled in this study. Blood samples were drawn just after induction of general anesthesia (basal samples), immediately after removal of the last gland, and at 5, 10, 15, and 30 minutes, and at the first morning after PTx. The assay was performed immediately after sample collection. Reductions of PTH levels were evaluated and expressed in percentage of basal levels. RESULTS: The mean PTH levels in 41 patients, excluding 3 in whom the PTH level did not drop significantly (>60 pg/ml), measured by QPTH at anesthesia, 0, 5, 10, 15, and 30 minutes were 734.3, 104.7, 58.8, 37.4, 27.0, 16.3 pg/ml, corresponding to 100%, 17.1%, 9.3%, 5.8%, 4.1%, 2.4% of the preexcision values, respectively. If the cutoff value was defined as 10.8% at 10 minutes, the sensitivity was 100% and specificity 90%. When the QPTH level dropped to under 10.8% at 10 minutes, we could consider that all glands were removed. CONCLUSIONS: QPTH in uremic patients is very useful to determine whether complete PTx is achieved during operation. PMID- 17354021 TI - Liver resection for metastases from renal cell carcinoma. AB - BACKGROUND: This study was conducted to evaluate the safety and efficacy of liver resection in patients with hepatic metastases from renal cell carcinoma and to identify selection criteria for patients suitable for resection. METHODS: Between January 1988 and March 2006, 31 patients underwent liver resection for metastases from renal cell carcinoma. Patients were identified from a prospective database and retrospectively reviewed. Patient, tumor, and operative parameters were analyzed for their influence on long-term survival. RESULTS: The overall 1-, 3- and 5-year survival rates were 82.2%, 54.3%, and 38.9%, respectively. One patient was deceased and 4 developed complications during the postoperative course. In the univariate analysis, site of the primary tumor (P = 0.013), disease-free interval (P = 0.012), and resection margins (P = 0.008) showed significant influence on long-term survival. In the multivariate analysis, only the resection margins were identified as an independent prognostic factor after liver resection. CONCLUSIONS: Liver resection is effective and safe in the treatment of patients with hepatic metastases from renal cell carcinoma and offers the chance of long-term survival and cure. Achieving a margin-negative resection is the most important criterion in the selection of suitable patients for liver resection. However, the number of patients in the present study was small, and investigations of larger series may provide further prognostic parameters in these patients. PMID- 17354023 TI - Commercial mesh versus nylon mosquito net for hernia repair. PMID- 17354025 TI - Platelets promote liver regeneration in early period after hepatectomy in mice. AB - BACKGROUND: Platelets contain several growth factors, including platelet-derived growth factor and hepatocyte growth factor. MATERIALS AND METHODS: We examined the effects of platelet increment on liver regeneration after 70% hepatectomy. Hepatectomies were carried out in male BALB/c mice, and subsequently divided into three groups: (i) untreated mice, (ii) thrombocytotic mice induced with thrombopoietin, and (iii) thrombocytopenic mice induced with anti-platelet antibody. Growth kinetics in the liver were analyzed as a function of the liver/body weight ratio, the mitotic index, the proliferating cell nuclear antigen labeling index and Ki-67 labeling index. Activation of signal transduction pathways relating to cell proliferation were examined, including the STAT3, Akt, and ERK1/2 pathways. Platelet accumulation in the residual liver was quantified by immunohistochemistry and transmission electron microscopy. RESULTS: In thrombocytotic and thrombocytopenic mice, liver/body weight ratios and Ki-67 labeling indices were significantly increased and significantly decreased, respectively, compared with untreated mice 48 hours post-hepatectomy. The Akt pathway was strongly activated, and platelet accumulation was significantly increased in thrombocytotic group 5 minutes post-hepatectomy compared with normal and thrombocytopenic groups. After hepatectomy platelets accumulated in the sinusoids of liver and promoted hepatocyte proliferation in early period after hepatectomy. CONCLUSION: By increasing or decreasing the platelet, marked changes in liver regeneration can occur, due to differences in cellular signaling and mitosis. PMID- 17354026 TI - Intrathyroid parathyroid adenoma in primary hyperparathyroidism: can it be predicted preoperatively? AB - INTRODUCTION: The role of cervical ultrasonography (US)-guided surgery for intrathyroid parathyroid adenoma in primary hyperparathyroidism is rarely reported. The aim of this study was to elucidate the role of cervical US in identifying this entity. METHODS: From 1996 to 2003, cervical explorations were performed in 178 patients (mean age 57 years) with primary hyperparathyroidism. High-resolution cervical US was performed in all of the patients. Patients' characteristics were reviewed to identify predictive factors for intrathyroid adenoma. RESULTS: Cervical US identified abnormal parathyroid glands in 163 of 178 patients, with a positive predictive value (PPV) of 100%. Six patients (3.4%) were found to have intrathyroid parathyroid adenomas (two in the superior parathyroid and four in the inferior parathyroid). Cervical US predicted this anomaly in four of six patients (67%) in whom the thyroid gland was not nodular and allowed total enucleation of the adenoma to be performed in three and subtotal thyroid loboisthmectomy in three; these operations were performed uneventfully and rapidly. The PPV in this anomaly was 80%. Thirteen patients required postoperative calcium supplementation for 2 to 4 months, and all were normocalcemic at the time of the last clinic visit, with follow-up varying from 12 to 96 months. On multivariable analysis, no factor predicted intrathyroid localization of parathyroid adenoma. CONCLUSIONS: The PPV of high-resolution cervical US for identifying an abnormal parathyroid gland was 100% in this series. It was 80% for predicting intrathyroid localization of the adenoma. This method allows us to shorten the operating time by guiding the exploration immediately toward the thyroid gland. PMID- 17354027 TI - Short-term tracking of atherosclerosis in operated and unoperated human carotid arteries by high resolution magnetic resonance imaging. AB - INTRODUCTION: A previous study demonstrated the efficacy of a phospholipid (PL) complexed with a protein (apoAI Milano) in causing 4.6% regression of atheroma volume as assessed by intravascular ultrasonography (IVUS) in a group of 47 patients with carotid atherosclerosis. The results of this study raised the question of whether the phospholipid alone could produce a similar effect. METHODS: To answer this question a trial of 39 subjects at five sites was designed. Patients with > 15% stenosis of at least one carotid artery as determined by US underwent intravenous PL (200 mg/kg) or placebo infusions weekly for 8 weeks. The wall/outer wall ratio, percent lipid-rich/necrotic core, and percent calcification were measured as a proportion of the vessel wall by magnetic resonance imaging (MRI) at 0, 4, 8, and 14 weeks. RESULTS: The substudy of seven of these patients evaluated at our site allowed comparison of the dimensions of five unoperated-unoperated carotid pairs and two operated unoperated pairs. In patient 1, MRI measurements on unoperated left and unoperated right carotids tracked almost identically over the 14-week study. Both carotids showed similar increases in the volumes of the total wall (+61% vs. 56%), the normal wall (+51% vs. 49%), and plaque (+99% vs. 85%). Both carotids showed similar decreases in lumen volume (-11% vs. -17%). The other four unoperated-unoperated carotid pairs showed dimensional changes over 14 weeks similar to those of patient 1. In patient 2, who underwent left endarterectomy, the operated carotid had a total artery volume of 2300 mm(3), about twofold greater than the unoperated carotid (1100 mm(3)). Operated and unoperated carotid measurements tracked in parallel. The unoperated carotid had volume increases of 25% (+200 mm(3)) in total wall, +19% (+100 mm(3)) in normal wall, and 43% (+75 mm(3)) in plaque. The operated carotid lumen showed no significant changes. Patient 7, who also underwent left endarterectomy, exhibited carotid changes similar to those of patient 2. CONCLUSIONS: Individual unoperated carotid pairs have volumes that track almost identically. In unilateral operated carotid pairs, the operated artery has 1.5- to 2.0-fold greater volume than unoperated carotids. In each of our two unilaterally operated patients, the operated carotid had decreased plaque volume (-3%, -58%), whereas the unoperated carotid had increased plaque volume (+43%, +7%). Among the five unoperated patients, one pair had 85%/99% increase in plaque volume; one pair had -15%/-10% decrease; and the other three pairs had intermediate changes. This study provides additional support to the view that unoperated human carotid arteries are bilaterally symmetrical. PMID- 17354028 TI - High incidence of tracheomalacia in longstanding goiters: experience from an endemic goiter region. AB - BACKGROUND: Our institute caters to a large number of patients with large, longstanding multinodular goiters; tracheal deviation and resulting airway problems like tracheomalacia are relatively common. However, the literature is sparse on the criteria of early diagnosis and optimum management of tracheomalacia, which our study highlights. METHODS: This retrospective study analyzed 900 thyroidectomies carried out during 1990-2005 for which data from 28 patients treated for tracheomalacia after thyroidectomy were available for analysis. Criteria for making a diagnosis of tracheomalacia after thyroidectomy included one or more of the following: normal vocal cord mobility, absence of glottic or subglottic edema or hematoma, soft and floppy trachea on palpation, obstruction to spontaneous respiration on gradual withdrawal of the endotracheal tube. RESULTS: Mean duration of thyroid enlargement was 13.75 years. Only 7 patients had a history of stridor. Tracheostomy was performed in 26 patients, and 2 patients were put on prolonged intubation. Tracheostomy was performed in 18 patients on the operating table, and 8 in the recovery room. The mean weight of the gland was 442 g and histopathology revealed that 11 cases were benign goiter. The tracheostomy tube was removed after an average of 8.5 days. There were no cases of tracheal stenosis on long-term follow-up. CONCLUSIONS: Patients with longstanding goiter, even when benign, are more prone to develop tracheomalacia. On the basis of our experience we strongly advocate tracheostomy intraoperatively if the trachea is soft and floppy and/or collapse of the trachea is observed following gradual withdrawal of the endotracheal tube. PMID- 17354029 TI - VEGF-C expression in squamous cell carcinoma and adenocarcinoma of the esophagus. AB - BACKGROUND: Vascular endothelial growth factor C (VEGF-C) is the only factor known to cause lymphangiogenesis. In esophageal cancer the histologic tumor type and lymph node metastasis are independent predictors of recurrence and poor outcome. To evaluate the rule of VEGF-C expression in esophageal cancer, we investigated 113 specimens, 59 squamous cell and 54 adenocarcinomas of the esophagus. METHODS: The expression of VEGF-C was evaluated using immunohistochemistry (IHC) on 59 paraffin-embedded archival specimens from patients with squamous cell esophageal carcinomas and 54 paraffin-embedded archival specimens of patients with esophageal adenocarcinomas arising in Barrett's mucosa. All patients had a complete tumor resection. A complete and updated follow-up was available for all patients. RESULTS: The expression of VEGF C was significantly different between the two histological types of esophageal tumors. Patients with squamous cell carcinoma and lymph node metastases had a significantly higher VEGF-C expression (P < 0.01). In patients with adenocarcinoma of the esophagus there was no correlation between VEGF-C expression and clinicopathological parameters. High VEGF-C expression tended to be correlated with poor survival in squamous cell cancer but not in adenocarcinoma of the esophagus. CONCLUSIONS: The present study indicates that VEGF-C may play a role in tumor progression via lymphangiogenesis in squamous cell carcinoma of the esophagus. This seems not to be true for the adenocarcinoma of the esophagus. These data could help with the understanding of the different onset and characteristics of lymph node metastasis in squamous cell carcinoma and adenocarcinoma of the esophagus. PMID- 17354030 TI - Comparison of outcomes following ileostomy versus colostomy for defunctioning colorectal anastomoses. AB - BACKGROUND: The present study evaluated outcomes of patients undergoing proximal diversion using either a loop ileostomy or loop colostomy following distal colorectal resection for malignant and non-malignant disease. METHODS: A literature search of the Medline, Ovid, Embase and Cochrane databases was performed to identify studies published between 1966 and 2006, comparing loop ileostomy and loop colostomy to protect a distal colorectal anastomosis. A random effect meta-analytical technique was used and sensitivity analysis performed on studies published since 2000, higher quality papers, those reporting on 70 or more patients, and those reporting outcomes following colorectal cancer resections. RESULTS: Seven studies, including three randomised controlled trials, satisfied the inclusion criteria. Outcomes of a total of 1,204 patients were analysed, of whom 719 (59.7%) underwent defunctioning loop ileostomy. High stoma output was more common following ileostomy formation (OR = 5.39, 95% CI: 1.11, 26.12, P = 0.04), but wound infections following their reversal were significantly fewer (OR = 0.21, 95% CI: 0.07, 0.62, P = 0.004). Overall complications were less frequent for ileostomy patients in the subgroup of high quality studies (OR = 0.22, 95% CI: 0.08, 0.59, P = 0.003). CONCLUSION: The results of this meta-analysis suggest that ileostomy may be preferable to colostomy when used to defunction a distal colorectal anastomosis. Wound infections following stoma reversal were reduced, as were overall stoma-related complications and incisional hernia following stoma reversal for ileostomy patients in high quality studies. PMID- 17354031 TI - Estimation of biologic gasification potential of arsenic from contaminated natural soil by enumeration of arsenic methylating bacteria. AB - Volatile arsenic species are found in gases released from natural environments as a result of natural ambient-temperature biomethylation of arsenic conducted by yeast, fungi, and bacteria. This process is part of arsenic transport in the arsenic geocycle. It is important to determine the flux of gasified arsenic released by microorganisms to determine the quantitative flux of arsenic cycle clearly and also to understand the effect of microorganisms on the transport and distribution of arsenic in the contaminated environment. In this study, biologic gasification potential of natural soil was determined by enumeration of arsenic methylating bacteria (AsMB). Enumeration of AsMB was conducted for 10 contaminated sites in Bangladesh where AsMB concentration varies from 0.2 x 10(4) to 7.8 x 10(4) most probable number (MPN) kg(-1) dry soil. The specific gasification rate of arsenic by microorganisms was estimated as 1.8 x 10(-7) microg As MPN(-1) d(-1) by incubation of soil in a laboratory soil column setup. Natural biologic gasification potential of arsenic was then calculated by multiplying the specific rate by the number of AsMB in different soils. The attempt of this study is a fundamental step in determining the volatilization flux of arsenic from land surface contributed by microorganisms. PMID- 17354032 TI - Environmental contamination of chrysotile asbestos and its toxic effects on antioxidative system of Lemna gibba. AB - Asbestos was monitored in various plant samples around an asbestos cement factory. Asbestos residue was found on the surface of all plant samples monitored. Based on asbestos concentration found in different plant samples during monitoring and on the property of asbestos to cause reactive oxygen species-mediated oxidative stress in animal models, laboratory experiments were conducted to assess the toxicity of chrysotile asbestos on an aquatic macrophyte, duckweed (Lemna gibba.). L. gibba plants were exposed to four concentrations (0.5, 1.0, 2.0, and 5.0 microg/mL) of chrysotile asbestos under laboratory conditions, and alterations in the glutathione and ascorbate antioxidative system were estimated at postexposure days 7, 14, 21, and 28 in order to assess changes in their level as suitable biomarkers of chrysotile contamination. Chrysotile exposure caused a decrease in total and reduced glutathione and an enhancement in the oxidized glutathione as well as the reduced/oxidized glutathione ratio. An increase in ascorbate pool size, and reduced as well as oxidized ascorbate was found to be accompanied by a decrease in the ratio of reduced/oxidized ascorbate. Alteration in the glutathione and ascorbate level might be considered as a biomarker of exposure to an unsafe environment because these are essential compounds of the general antioxidative strategy to overcome oxidative stress due to environmental constraints. Because an increase in the oxidation rate of antioxidants weakens cellular defenses and indicates a precarious state, they could constitute indicators of toxicity. PMID- 17354033 TI - Acute and sublethal toxicities of rotenone in juvenile rainbow trout (Oncorhynchus mykiss): swimming performance and oxygen consumption. AB - Rotenone, a natural insecticide and piscicide, was shown to have an extremely small margin between no lethality (5.0 microg/L) and 100% mortality (6.6 microg/L) for static-renewal 96-hour toxicity tests with juvenile rainbow trout (Oncorhynchus mykiss). Dissolved organic carbon (DOC) at concentrations of 3.0 and 4.0 mg/L significantly increased the rotenone 96-hour LC(50) (median lethal concentration) from 5.80 microg/L (confidence interval (CI) 5.51 to 6.10) to 6.55 microg/L (CI 6.28 to 6.83) and 7.75 microg/L (CI 7.29 to 8.24), respectively, probably as a result of rotenone adsorption onto DOC, which decreased its bioavailability. Using concentrations of 0, 3.0, 4.0, and 5.0 microg/L rotenone and exposure periods of 2, 4, 6, 12, 16, 24, and 48 hours, the threshold concentration of rotenone for impairment of critical swimming performance (Ucrit) was 3.0 microg/L (P = 0.029), with no further impairment at higher concentrations and no time-dependent effect on Ucrit. Using continuous measures of oxygen uptake for 48 hours before and 48 hours during rotenone exposure (0, 1.5, 2.5, 3.0, and 3.5 microg/L), rotenone significantly decreased peak active oxygen uptake at all rotenone concentrations tested without affecting routine oxygen uptake. Fish were individually chased and then placed in rotenone concentrations of 0, 1.0, 3.0, 4.0, 5.0, and 6.0 microg/L to monitor initial postexercise oxygen uptake (Mo2Max) and excess postexercise oxygen consumption (EPOC) during a 40-minute recovery period. Rotenone significantly decreased Mo2Max (P = 0.002) after exposures to 4.0 and 5.0 microg/L, but not 6.0 microg/L, without affecting EPOC. PMID- 17354034 TI - Cadmium exposures in fathead minnows: are there sex-specific differences in mortality, reproductive success, and Cd accumulation? AB - The primary goal of this experiment was to determine whether cadmium (Cd) exposure has sex-specific effects on the reproductive success of fathead minnows as measured by time to first spawn, spawning frequency, clutch size, fecundity, fertilization success, hatching success, and offspring mortality to 2 d post hatch. Prior to breeding, minnows were either exposed to 50 microg/L Cd or sham exposed for 21 d. After exposures, minnows were paired (male x female) into one of four breeding groups-control x control (C x C), control x exposed (C x E), exposed x control (E x C) or exposed x exposed (E x E). Pairs of minnows were subjected to a 21-d breeding study during which the reproductive parameters mentioned above were measured. During the breeding study, minnows in the E x E pairs had significantly higher mortality than minnows in the C x C pairs; however, the mortality of minnows in the C x E and E x C did not differ from that of C x C pairs. Presumably, behavioral alterations in both males and females exposed to Cd accounted for the increased mortality in the E x E group. The results of the breeding study did not reveal any significant differences among any of the reproductive parameters measured with the exception of offspring mortality. Offspring from C x E pairs did not differ from offspring from C x C pairs with regard to mortality; however, offspring from pairs containing exposed males (E x C and E x E) had significantly higher mortality than offspring from C x C pairs suggesting that paternal exposure to Cd leads to an increase in offspring mortality. PMID- 17354035 TI - Mass flow of polycyclic musks in two wastewater treatment plants. AB - Synthetic musks are found in varying amounts in many consumer products. After use, synthetic musks go down the drain into the sewer system and then reach wastewater treatment plants (WWTPs). In this study, mass flows of two synthetic polycyclic musks, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[gamma]-2 benzopyran (HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronaphthalene (AHTN), along with HHCB-lactone (the oxidation product of HHCB) were examined in two WWTPs. Wastewater and sludge samples were collected at various stages of the treatment process for analysis. HHCB, AHTN, and HHCB lactone were found in all wastewater samples at concentrations in the ranges of 1780 to 12700, 304 to 2590, and 146 to 4000 ng/L, respectively. The highest concentrations for all compounds were found in sludge samples. Sludge samples contained HHCB at 7.23 to 108 mg/kg dry weight, AHTN at 0.809 to 16.8 mg/kg dry weight, and HHCB-lactone at 3.16 to 22.0 mg/kg dry weight. This is the first study to report HHCB-lactone in wastewater and HHCB, HHCB-lactone, and AHTN in sludge in WWTPs from the United States. HHCB and AHTN concentrations decreased during treatment. However, the concentrations of HHCB-lactone increased in water after treatment. Based on the daily flow rates and mean concentrations of the three compounds in effluent, a WWTP representative of those studied here is expected to release 288 g HHCB, 60.4 g AHTN, and 158 g HHCB-lactone/100,000 people/d. Partitioning HHCB, AHTN, and HHCB-lactone to sludge is the major removal mechanism for polycyclic musks in WWTPs. PMID- 17354036 TI - Trophic transfer of polychlorinated biphenyls in great blue heron (Ardea herodias) at Crab Orchard National Wildlife Refuge, Illinois, United States. AB - In this study, polychlorinated biphenyl (PCB) concentrations were measured in great blue heron (GBHE) (Ardea herodias) chicks and eggs at Crab Orchard National Wildlife Refuge (CONWR) in southern Illinois. In addition, biomagnification factors (BMFs) from gizzard shad (Dorosoma cepedianum) and their effects on reproductive effort were examined. Total PCBs (SigmaPCBs) in chicks and shad were greater at the east end of Crab Orchard Lake (i.e., near the site of contamination) than the west end, but chick concentrations (4.1 to 10.1 mg/kg lipid weight) were lower than those typically associated with adverse effects. Chick BMFs based on shad from diet samples were greater than those based on shad collected from the lake. Furthermore, the two shad sources had dissimilar dioxin like congener patterns and SigmaPCBs, suggesting that there was variation in PCB load and composition and that the more contaminated shad were a small proportion of the actual heron chick diet. The number of eggs laid per nest was similar between colonies, suggesting no observable population level effects. Further study may be necessary to evaluate long-term effects on GBHEs at CONWR. PMID- 17354037 TI - Persistent organic pollutants in sediments from Sai Gon-Dong Nai River basin, Vietnam: levels and temporal trends. AB - Surficial sediment samples were collected from Hochiminh City canals, the Sai Gon Dong Nai River, and its estuary, one of the most predominant industrial areas in Hochiminh City, southern Vietnam, for determination of selected persistent organic pollutants (POPs). Contamination pattern was as follows: PCBs > or = DDTs > HCB > CHLs > HCHs. Concentrations of PCBs and DDTs ranged from 0.50-150 ng/g and 0.15-72 ng/g dry wt, respectively. On the other hand, concentrations of CHLs, HCHs, and HCB were mostly <2 ng/g dry wt. Levels of the all organochlorines (OCs) in Hochiminh City canals were significantly higher than those in the other areas, indicating the urban areas as major pollution sources to the aquatic environment. The contamination pattern was PCBs > DDTs in the city canals but PCBs < DDTs in the downstream and the estuary, suggesting particularly high contamination by PCBs in the city. Examination of DDTs composition and their ratios demonstrated continuous input of this pesticide to the city canals. However, the combination of our data and those from available literature implies a decreasing trend of PCBs and DDTs in the environment. DDTs concentrations have been reduced 50% after approximately 5 years. Composition of CHLs in the sediment from Hochiminh City canals was comparable to those of common technical mixtures, suggesting continuous input of CHLs to the environment. CHLs might be in use for purposes like termite control, wood preservation, and protection of underground cables. Hazard assessment implies high toxic potential of DDTs for sediments from Hochiminh City canals and suggests the need for better management of municipal discharges. PMID- 17354038 TI - Polybrominated hexahydroxanthene derivatives (PBHDs) and other halogenated natural products from the Mediterranean sponge Scalarispongia scalaris in marine biota. AB - Structures of polybrominated hexahydroxanthene derivatives (PBHDs) previously detected in commercial fish from the Mediterranean Sea and mussels from New Zealand were assigned to 2,7-dibromo-4a-bromomethyl-1,1-dimethyl-2,3,4,4a,9,9a hexahydro-1H-xanthene (TriBHD) and 2,5,7-tribromo-4a-bromomethyl-1,1-dimethyl 2,3,4,4a,9,9a-hexahydro-1H-xanthene (TetraBHD) by comparing their gas chromatography/mass spectrometry (GC/MS) features with isolates from an Australian sponge of the Cacospongia genus. Because of the geographic distance between the Mediterranean Sea in Europe (origin of the fish) and Australia (origin of the sponge), a closely related sponge, Scalarispongia scalaris, was collected in the Mediterranean Sea and analyzed for PBHDs and other halogenated compounds. The Mediterranean sponge contained the PBHDs at 37 mg/kg dry weight. Using quantitative standards for the first time, the PBHD concentrations in fish and mussel samples published earlier were re-examined. Concentrations of up to 1 mg/kg TriBHD and 0.5 mg/kg TetraBHD were determined in the lipids. No correlation with 2,2', 4,4', 5,5'-hexachlorobiphenyl (PCB 153) or p,p'-DDE was found, which is in agreement with other marine halogenated natural products detected in the fish samples. Besides the PBHDs, further unknown halogenated compounds were detected in the Mediterranean sponge, some of which were also detected in commercial fish. GC/electron ionization-MS analysis showed that a major mixed halogenated compound in the sponge had a molecular ion at m/z 480 and contained three bromines, three chlorines, and 9-10 carbons. No corresponding structure has been described for this feature in the scientific literature. This sponge secondary metabolite and potential novel halogenated natural product was also detected in commercial fish. Another prominent mixed halogenated compound detected both in sponge and fish was the dibromotrichloro monoterpene MHC-1 (C(10)H(13)Br(2)Cl(3)). PMID- 17354039 TI - Trace elements in three marine birds breeding on Reunion Island (Western Indian ocean): part 2-factors influencing their detoxification. AB - Seabird tissues collected between 2002 and 2004 from Barau's Petrel (Pterodroma baraui), Audubon's Shearwater (Puffinus lherminieri bailloni), and White-Tailed Trop icbird (Phaethon lepturus) colonies on Reunion Island were analyzed for metallothioneins (MTs) and trace element content. The subcellular distribution between soluble and insoluble fractions of Cd, Cu, Fe, Mn, Se, and Zn was determined in liver and kidney. In both, the soluble fraction of the cell concentrated most of the Cd and Se, whereas Fe, Mn, and Zn were preferentially accumulated in the insoluble fraction. The distribution of these elements varied with the tissue, age of the bird, and species. Furthermore, the distributions of Fe and Mn were somewhat influenced by the bird's physical condition. MT levels were measured in the soluble fraction after heat denaturation. The levels of these proteins varied from 5.5 +/- 2.7 mg x g(-1) dry weight (dw) to 11.4 +/- 6.2 mg x g(-1) dw depending on the species and the tissue considered. MT levels were significantly different between liver and kidney only in the White-Tailed Tropicbird. In the three species, MT levels in kidney were significantly higher in adult than juvenile birds. The bird's weight also had an influence on hepatic and renal MT levels, but not the sex nor the reproductive status. The implication of MTs in Cu and Zn homeostasis and Cd and Hg detoxification are discussed. In addition, clues on Hg regulation by Se were found, especially in Barau's Petrel, where the levels of these two elements were significantly correlated. PMID- 17354040 TI - Polycyclic aromatic hydrocarbons and ecotoxicological characterization of seawater, sediment, and mussel Mytilus galloprovincialis from the Gulf of Rijeka, the Adriatic Sea, Croatia. AB - The pattern of spatial distribution of polycyclic aromatic hydrocarbons (PAHs) in seawater, sediment, and mussels, potential toxicity of different matrices, and mussel anoxic survival from six sampling sites of the Gulf of Rijeka, the Adriatic Sea, Croatia was examined. The total concentrations of 10 PAHs vary from below detection limit to 305 ng/L in seawater, from 213 to 695 microg/kg dry weight in sediment and from 49.2 to 134 ng/g wet weight in mussel tissue. Combustion is the principal source of PAH contamination in seawater and sediment samples. Sediment samples are distinguished from the majority of seawater and mussel samples by the presence of high molecular weight PAHs, whereas mussels from majority of sampling sites tend to accumulate PAHs of lower molecular weight. The PAH dynamic between different matrices is complex and site specific. Toxicity of seawater and sediment organic extract is correlated with PAH content, indicating that PAHs are the predominant toxic compounds. There is no correlation between toxicity of mussel biological fluids and toxicity of seawater and sediment, or between toxicity of mussel biological fluid and PAH content in mussel, seawater, or sediment. There is a positive correlation between potential toxicity of mussel biological fluids and reduction of anoxic survival time. Mussel anoxic survival is influenced by the presence of complex mixture of toxic contaminants, not only PAHs. The relationship between PAH contents in different marine matrices and their ability to affect mussels revealed specific interactions between an organism and complex mixture of toxic contaminants present in the marine environment. PMID- 17354041 TI - Growth and reproduction of earthworms in ultramafic soils. AB - Ultramafic soils are characterized by high concentrations of heavy metals of natural origin-such as chromium, cobalt, manganese, and nickel-as well as a shortage of primary nutrients. This can result in extremely disadvantageous living conditions for all soil-dwelling organisms. Responses to these conditions were addressed by studying growth, cocoon production, and fecundity of earthworms as endpoints of sublethal effects and how this influences the reproductive system and, consequently, population development. Mature specimens of two ecophysiologically different species of earthworms, Eisenia fetida (Savigny) and Aporrectodea caliginosa (Savigny), were exposed for 56 days to an uncontaminated soil and ultramafic soils collected from six ultramafic sites in the Barberton greenstone belt. In all ultramafic soil samples, the specimens of both species grew slower than those in the control soil. In A. caliginosa, an autotomization of the tail section was observed at higher concentrations of heavy metals. At high levels of heavy metals such as manganese, chromium, nickel, and cobalt, a significantly lower cocoon production was recorded for E. fetida, and at medium levels, a time delay in cocoon production was found. A. caliginosa showed an increase in production at medium levels and a decrease at high levels of heavy metals. In both species, no correlation between growth and cocoon viability was found, indicating different target levels for toxicants present in ultramafic soils. To determine effects of these soils on population dynamics, hatching success may be a more useful endpoint of reproduction. PMID- 17354043 TI - Mortality in peripheral arterial disease: a comparison of patients managed by vascular specialists and general practitioners. AB - BACKGROUND: Peripheral arterial disease (PAD) is undertreated by general practitioners (GPs). However, the impact of the suboptimal clinical management is unknown. OBJECTIVE: To assess the mortality rate of PAD patients in relation to the type of physician who provides their care (GP or vascular specialist). DESIGN: Prospective study. SETTING: Primary care practice and academic vascular laboratory. PARTICIPANTS: GP patients (n = 60) were those of the Peripheral Arteriopathy and Cardiovascular Events study (PACE). Patients managed by specialists (n = 82) were consecutive subjects with established PAD who were referred to our vascular laboratory during the enrollment period of the PACE study. MEASUREMENTS: All-cause and cardiovascular mortality. RESULTS: After 32 months of follow-up, specialist management was associated with a lower rate of all-cause mortality (RR = 0.04; 95% CI 0.01-0.34; p = .003) and cardiovascular mortality (RR = 0.07; 95% CI 0.01-0.65; p = .020), after adjustment for patients' characteristics. Specialists were more likely to use antiplatelet agents (93% vs 73%, p < .001), statins (62% vs 25%, p < .001) and beta blockers (28% vs 3%, p < .001). Survival differences between specialists and GPs disappeared once the use of pharmacotherapies was added to the proportional hazard model. The fully adjusted model showed that the use of statins was significantly associated with a reduced risk of all-cause mortality (RR = 0.02; 95% CI 0.01-0.73, p = .034) and cardiovascular mortality (RR = 0.02; 95% CI 0.01-0.71, p = .033). CONCLUSIONS: Specialist management of patients with symptomatic PAD resulted in better survival than generalist management. This effect appears to be mainly caused by the more frequent use of effective medicines by specialists. PMID- 17354044 TI - Exposure and health risk of gallium, indium, and arsenic from semiconductor manufacturing industry workers. PMID- 17354042 TI - The application of positron-emitting molecular imaging tracers in Alzheimer's disease. AB - The symptomatology and known pathology of Alzheimer's disease are restricted to the central nervous system. This review details studies of PET tracers aimed at interrogating cholinergic, serotonergic, opiate, benzodiazepine, and inflammatory pathways as well as PET tracers that illuminate amyloid plaques and neurofibrillary tangles in AD. Progress has been remarkable. Together with studies of brain structure with MRI and of functional regional brain activity, e.g., through measures of blood flow and glucose metabolic rate, molecular imaging promises to dramatically alter our understanding of the structural and physiological abnormalities underlying AD symptomatology. A more immediate impact on the diagnosis and treatment evaluation of AD patients in clinical trials is predicted while the possibility of personalized treatment or prevention of AD may not be that far away. PMID- 17354045 TI - Effect of surfactant on leaching of pendimethalin in Florida Candler fine sand. PMID- 17354062 TI - Lactate and malignant tumors: a therapeutic target at the end stage of glycolysis. AB - Metabolic aberrations in the form of altered flux through key metabolic pathways are primary hallmarks of many malignant tumors. Primarily the result of altered isozyme expression, these adaptations enhance the survival and proliferation of the tumor at the expense of surrounding normal tissue. Consequently, they also expose a unique set of targets for tumor destruction while sparing healthy tissues. Despite this fact, development of drugs to directly target such altered metabolic pathways of malignant tumors has been under-investigated until recently. One such target is the ultimate step of glycolysis, which, as expected, presents itself as a metabolic aberration in most malignant tumors. Termed "aerobic glycolysis" due to abnormal conversion of pyruvic acid to lactic acid even under normoxia, the altered metabolism requires these tumors to rapidly efflux lactic acid to the microenvironment in order to prevent poisoning themselves. Thus, exposed is a prime "choke-point" to target these highly malignant, frequently chemo- and radio- resistant tumors. This review will focus on current outcomes in targeting lactate efflux in such tumors using glioma as a model, an ongoing project in our laboratory for the past half-decade, as well as supporting evidence from recent studies by others on targeting this "tail-end" of glycolysis in other tumor models. PMID- 17354063 TI - Molecular characterization and genetic organization of the inhibitor of apoptosis gene (iap-5) region of the Pieris rapae granulovirus. AB - Pieris rapae granulovirus (PiraGV) is a baculovirus pathogenic to the insect P. rapae (Pieridae, Lepidoptera). Though being known for decades, information on the genetic organization of this virus remains limited. In an effort to characterize this virus, an 11.8 kb BamHI restriction fragment that harbors the inhibitor of apoptosis gene (iap-5) was sequenced. Our results indicate that this region contains important genes such as dnapol, lef-3, lef-9, and dnaligase that are involved in transcription and replication of the virus. The gene content and synteny in this region are highly conserved among granulovirus genomes. Phylogenetic analysis showed that PiraGV genes are more closely related to the Choristoneura occidentalis granulovirus (ChocGV) than other characterized granulovirus (GVs). PMID- 17354064 TI - Social skills differences among attention-deficit/hyperactivity disorder types in a chat room assessment task. AB - This study assessed social skills in 116 children aged 7-12 with ADHD-Combined Type (ADHD-C; n=33), ADHD-Inattentive Type (ADHD-I; n=45), and comparison children (n=38), with consideration of the role sluggish cognitive tempo (SCT) symptoms play in distinguishing profiles. Social skills were assessed using a novel computerized chat room task, in which participants were encouraged to join a conversation and type messages to interact with four computer-simulated peers. Every participant received the identical stimulus from the simulated peers, but was free to respond to it in his or her own unique way. Relative to comparison children, children with ADHD-C made off-topic and hostile responses; children with ADHD-I made off-topic responses, few responses and showed poor memory for the conversation. ADHD subtype differences remained after statistical control of IQ, reading achievement, typing skill, and comorbid disruptive behavior disorders. SCT symptoms, most prevalent among children with ADHD-I, predicted a distinct pattern of social withdrawal and lower hostility. Parent and teacher ratings and in-vivo observations of social skills correlate with this new measure. PMID- 17354065 TI - Are pain intensity and pain related fear related to functional capacity evaluation performances of patients with chronic low back pain? AB - INTRODUCTION: Pain related fear and pain intensity have been identified as factors negatively influencing Functional Capacity Evaluation (FCE) performances in patients with CLBP. Conflicting results have been reported in the literature. The objective of this study was to analyze the relationships between pain intensity and pain-related fear on the one hand, and performances during an FCE on the other hand in two samples of patients with chronic low back pain (CLBP). METHODS: Two cross sectional observation studies were performed with two samples of patients with CLBP (study 1: n = 79; study 2: n = 58). Pain related fears were operationally defined as the score on the Tampa Scale of Kinesiophobia in study 1, and the Fear Avoidance Beliefs Questionnaire (FABQ) in study 2. Pain intensity was measured with a Numeric Rating Scale in both studies. Avoidance behavior observed during FCE was in both studies operationally defined as the unwillingness to engage in high intensity performance levels of three different functional activities: high intensity lifting, prolonged standing in a forward bend position, and fast repetitive bending at the waist. RESULTS: A total of 25 correlations between pain and pain related fear, and performance variables were calculated, out of which 7 were significant (p < 0.05). The strength of these significant correlations ranged from r = -0.23 to r = -0.50. Multivariate linear regression analyses revealed non-significant relationships in most instances. Pain and pain related fear contributed little if any to these models. CONCLUSIONS: The relation between pain and pain related fear and FCE performance is weak or non-existent in patients with CLBP. PMID- 17354066 TI - Genetic and environmental influences on adult life outcomes: evidence from the Texas Adoption Project. AB - A short mail questionnaire was sent to individuals, now adults, who had been studied over 30 years ago as children in the Texas Adoption Project. Their parents and (in many cases) siblings also described them using the same questionnaire, and the parents described themselves as well. The questionnaire was designed to obtain information about educational, occupational, and marital outcomes, as well as adult problems and personality. Results were obtained for 324 adopted and 142 biological children from the original 300 families, and for 266 parents. Although both the adopted and biological offsprings' outcomes were generally positive, those for the adopted offspring were somewhat less so. Biologically related family members tended to be more similar in their life outcomes than biologically unrelated family members, suggesting that genes were playing an important role. PMID- 17354067 TI - Dissecting the cognitive and neural basis of emotional abnormalities. PMID- 17354069 TI - Altered experience of emotion following bilateral amygdala damage. AB - It has been well established that the amygdala is critical for processing various aspects of emotion, and in particular, for the perception of negative emotions such as fear. Perhaps the strongest evidence for this conclusion in humans comes from an extensive series of investigations in patient SM, an extremely rare neurological patient who has complete, focal bilateral amygdala damage. One question that has remained unanswered, however, is whether SM has a normal phenomenological experience of emotion, especially negative emotion. To explore this issue, we designed a study in which two experienced clinical psychologists conducted "blind" interviews of SM (the psychologists were not provided any background information regarding SM), with a special emphasis regarding the nature of her emotional experience. Both of them reached the conclusion that SM expressed a normal range of affect and emotion, and neither felt that SM warranted a DSM-IV diagnosis. However, they both noted that SM was remarkably dispassionate when relating highly emotional and traumatic life experiences, and they noted that she did not seem to have a normal sense of distrust and "danger". To the psychologists, SM came across as a "survivor", as being "resilient" and even "heroic" in the way that she had dealt with adversity in her life. In the full light of SM's neurological and neuropsychological profile, however, these observations reflect the fact that SM is missing from the experiences in her life some of the deepest negative emotions, in a manner that parallels her defect in perceiving such emotions in external stimuli. These findings have interesting parallels with recent animal work (cf. Bauman, Lavenex, Mason, Capitanio, & Amaral, 2004a), and they provide valuable insights into the emotional life of an individual with complete bilateral amygdala damage. PMID- 17354070 TI - The neural basis of mood dysregulation in bipolar disorder. AB - Bipolar disorder is characterised by affective instability and mood dysregulation. Understanding of the neural mechanism underlying this remains limited, however. Here, findings will be described from studies that have employed neuroimaging techniques to measure neural responses to emotionally salient stimuli in individuals with the disorder. These findings will be discussed in relation to a theoretical framework previously proposed for understanding the separate cognitive processes underlying emotion perception to allow the formulation of a postulated neural mechanism for the mood dysregulation in bipolar disorder. PMID- 17354068 TI - Anterior medial temporal lobe in human cognition: memory for fear and the unexpected. AB - INTRODUCTION: To survive, an organism must remember occurrences of value in its environment. These include those that pose a threat to survival, novel or unexpected stimuli, or a general class of stimuli that represent punishment or reward. There is substantial evidence that memory for novel and emotionally salient events is enhanced relative to familiar or emotionally neutral events. METHODS: We present human functional magnetic resonance imaging (fMRI) experiments that address the neurobiological processes underlying upregulation of memory for novel or emotional events. RESULTS: Enhanced memory for novel or unexpected stimuli is mediated by anterior hippocampus, whereas increased memory for emotional stimuli is mediated by a beta-adrenergic-dependent modulation of amygdala-hippocampal interactions. We introduce a hypothesis that medial temporal connectivity with autonomic control centres may be central to this memory enhancement. CONCLUSION: Enhanced memory for stimuli that are of adaptive importance to survival is mediated by the anterior medial temporal lobe and effected via connections with the autonomic system. PMID- 17354071 TI - Emotional processing in schizophrenia. AB - INTRODUCTION: Persons with schizophrenia have impaired emotional processing, involving experience, expression, and recognition of emotions. METHODS: This article reviews the historical descriptions and more recent work on emotion processing in schizophrenia. RESULTS: Although abilities of emotional processing relate directly to interpersonal communication and psychosocial functioning, methodological issues exist in the current body of studies and resultant knowledge, which limit translation to novel treatment options. CONCLUSIONS: Further improvement in emotion processing in persons with stable schizophrenia are unlikely to result from conventional pharmacotherapy of psychosis. New treatment modalities and behavioural interventions offer possible improvements in quality of life and psychosocial functioning. PMID- 17354072 TI - Object-location memory in schizophrenia: interference of symbolic threatening content. AB - INTRODUCTION: Monitoring environmental stimuli for their emotional relevance is inherently associated with spatial processing. In schizophrenia, deficits in spatial working memory on one hand, and abnormal emotion processing on the other, have been documented, but these have not been related to each other. In the present study, we investigated whether a specific aspect of spatial memory (i.e., object-location memory), is impaired in patients with schizophrenia. Moreover, we hypothesised that symbolic threatening content of objects would interfere with spatial processing in patients with schizophrenia but not in healthy controls. METHODS: Spatial memory for symbolic pictorial stimuli was assessed in 40 patients with schizophrenia compared to 41 healthy matched control participants using an object-relocation task. RESULTS: Patients with schizophrenia performed worse in relocating objects, independent of overall intellectual ability. More specifically, patients were particularly worse in the relocation of objects with a symbolic threatening content. CONCLUSIONS: These results suggest that a threatening semantic emotional content of schematic stimuli can interfere with spatial processing in schizophrenia. We hypothesise that a disproportional influence of the amygdala on other brain areas, such as the hippocampus, might underlie this specific emotional interference. PMID- 17354073 TI - Unmasking feigned sanity: a neurobiological model of emotion processing in primary psychopathy. AB - INTRODUCTION: The neurobiological basis of primary psychopathy, an emotional disorder characterised by a lack of fear and empathy, on the one hand, and extremely violent, antisocial tendencies, on the other, is relatively unknown. Nevertheless, theoretical models that emphasise the role of fearlessness, imbalanced motivation, defective somatic markers, and dysfunctional violence inhibition mechanisms have complementary proposals regarding motivations and brain mechanisms involved. METHODS: Presently, incorporating the heuristic value of these models and further theorising on the basis of recent data from neuropsychology, neuroendocrinology, neuroimaging, and repetitive transcranial magnetic stimulation (rTMS), an attempt is made to construct a neurobiological framework of emotion processing in primary psychopathy with clinical applicability. RESULTS: According to this framework, defective emotional processing in primary psychopathy results from bottom-up hormone-mediated imbalances at: (1) the subcortical level; (2) in subcortico-cortical "cross talk"; that end up in an instrumental stance at the cortical level (3). An endocrine dual-system approach for the fine-tuned restoration of these hormone mediated imbalances is proposed as a possible clinical application. DISCUSSION: This application may be capable of laying a neurobiological foundation for more successful sociotherapeutic interventions in primary psychopathy. PMID- 17354074 TI - Toward a framework for defective emotion processing in social phobia. AB - INTRODUCTION: This paper explores and outlines an evolutionary approach to understanding social phobia (SP) as a developmental disorder in brain mechanisms that regulate socioemotional behaviour. METHODS: A literature review of cognitive, neuronal, and endocrine correlates of SP is presented using an integrative approach. RESULTS: Social phobia patients present with a specific and developmentally stable functional neuroanatomical and neuroendocrine profile that can be linked to findings of cognitive attentional abnormalities. CONCLUSIONS: It is argued that SP is the human counterpart to primate sub-ordination stress and develops from clearly identifiable precursors in early child-hood, the understanding of which requires fundamental insights into the regulation of socioemotional behaviour. The current state of knowledge speaks strongly in favour of a diathesis model, in which distorted cognitions that are characteristic of SP are secondary to hyperexcitability of fear circuits that set off at least as early as at preverbal ages and ultimately may lead to the development of SP. PMID- 17354075 TI - Cognitive neuropsychology of alexithymia: implications for personality typology. AB - INTRODUCTION: We examine the cognitive neuroscience of the five components of the alexithymia syndrome, and propose a classification of alexithymia types based on psychobiological traits. METHOD: Literature review. RESULTS: The following neural structures have been shown to be prominent in emotional function: right and left hemisphere, corpus callosum, anterior commissure, anterior cingulate, prefrontal cortex, amygdala, and insular cortex. The specific relevance of these structures to alexithymia is discussed. CONCLUSIONS: The following conclusions and/or propositions are presented: The right hemisphere produces a global, nonverbal overview of emotional information; the left hemisphere seems dedicated to analysing emotions and higher explicit emotional cognitions. Both orbitoprefrontal cortices are important in affective aspects of alexithymia, while right temporal cortex is involved in cognitive aspects. Two subparts of anterior cingulate fulfil functions in the affective and cognitive dimensions of alexithymia. The amygdalae are involved in both cognitive and affective aspects. All structures mentioned can modulate one another. The role of interhemispheric information transfer via the corpus callosum and the anterior commissure is also discussed. The evidence that that cognitive processing of emotional information inhibits affective processing of such information is discussed in terms of its implications for a theory of alexithymia subtypes. PMID- 17354077 TI - Reduced sensitivity in the recognition of anger and disgust in social anxiety disorder. AB - INTRODUCTION: The aim of this study was to investigate the recognition of facial expressions in patients with a generalised social anxiety disorder. It is well documented that in different psychiatric disorders (e.g., depression, schizophrenia) patients may show an altered processing of emotions. However, in generalised social anxiety, emotion recognition has not been studied. METHODS: 24 Patients with generalised social anxiety disorder and 26 healthy controls, matched on age, education, and sex were included. The task entailed the emotional labelling of faces with different facial expressions (happiness, fear, disgust, sadness, surprise, anger) presented in different intensities. Subjects were asked to make a forced-choice response. RESULTS: These revealed that patients with a generalised social anxiety disorder were less sensitive for the negative facial expressions of anger and disgust compared to the control group. CONCLUSIONS: This deficit could play a role in the development and/or the maintaining of the social anxiety. Both explanations are discussed. PMID- 17354078 TI - The inferiority complex in paranoia readdressed: a study with the Implicit Association Test. AB - INTRODUCTION: It has been theorised that patients with persecutory delusions display a lack of covert self-esteem (formerly termed the 'inferiority complex'), while at the same time displaying normal or even heightened levels of explicit self-esteem. However, the empirical basis for this assumption is inconsistent. METHODS: In view of apparent shortcomings of prior studies to assess implicit self-esteem, the Implicit Association Test was utilised to readdress this theory. The Rosenberg scale served as an index of overt self-esteem. A total of 23 schizophrenic patients, 13 of whom showed current symptoms of persecutory delusions, participated in the study; 41 healthy and 14 depressed participants served as controls. RESULTS: Schizophrenic patients showed decreased levels of both implicit and explicit self-esteem relative to healthy controls. In line with recent studies, patients with current ideas of persecutory delusions displayed greater explicit self-esteem than nonparanoid patients. CONCLUSIONS: The present study lends partial support for the notion that persecutory delusions serve as a defence against low implicit self-esteem, although the explicit self-esteem of these patients is still lower than in normal participants. Apart from abnormalities of attributional style, which have been assumed to convert low into high self-esteem, the assumption that a 'feeling of personal significance' heightens self-esteem in paranoid schizophrenia deserves further consideration. PMID- 17354076 TI - Social and emotional functions in three patients with medial frontal lobe damage including the anterior cingulate cortex. AB - INTRODUCTION: The aim of this study was to explore social and emotional functions in patients with medial frontal damage including the anterior cingulate cortex (ACC). METHODS: Three patients with medial frontal lobe lesions primarily involving the ACC performed tasks on motivational decision making, emotional facial expression recognition, and social cognition, including theory of mind (ToM). Their performance on these tasks was compared with age and education matched healthy controls. RESULTS: Patient performance on the motivational decision making and social situations tasks did not differ from controls. Selective emotional facial expression recognition impairment for fear was evident in one patient with a unilateral right ACC lesion (patient 3). ToM impairment was present in only one patient with a bilateral ACC lesion (patient 2). In contrast, the two patients with unilateral right ACC lesions had intact ToM (patients 1 and 3). CONCLUSIONS: These findings suggest that medial frontal lobe lesions primarily involving the ACC do not appear to critically disrupt motivational decision making or social situation processing. The ACC plays a role in processing particular types of emotion (fear). Bilateral ACC damage impairs ToM processing, but unilateral damage to the right ACC is not sufficient to disrupt ToM. PMID- 17354079 TI - Theory of mind and perceptual context-processing in schizophrenia. AB - INTRODUCTION: A series of studies have suggested that schizophrenia patients are deficient in theory of mind (ToM). However, the cognitive mechanisms underlying ToM deficits in schizophrenia are largely unknown. The present study examined the hypothesis that impaired ToM in schizophrenia can be understood as a deficit in context processing. METHODS: Disorganised schizophrenia patients (N = 12), nondisorganised schizophrenia patients (N = 36), and nonpsychotic psychiatric patients (N = 26) were tested on three ToM tasks and a visual size perception task, a measure of perceptual context processing. In addition, statistical analyses were carried out which compared chronic, treatment-refractory schizophrenia patients (N = 28) to those with an episodic course of illness (N = 20). RESULTS: Overall, ToM performance was linked to deficits in context processing in schizophrenia patients. Statistical comparisons showed that disorganised as well as chronic schizophrenia patients were more impaired in ToM but more accurate in a visual size perception task where perceptual context is misleading. CONCLUSIONS: This pattern of results is interpreted as indicating a possible link between deficits in ToM and perceptual context processing, which together with deficits in perceptual grouping, are part of a broader dysfunction in cognitive coordination in schizophrenia. PMID- 17354082 TI - A case of evolving post-ictal language disturbance secondary to a left temporal arteriovenous malformation: jargon aphasia or formal thought disorder? AB - INTRODUCTION: Wernicke's dysphasia and formal thought disorder are regarded as distinct diagnostic entities although both are linked to pathology in the left superior temporal gyrus (STG). We describe a patient with focal pathology in the left STG, giving rise acutely to a fluent dysphasia, which gradually evolved into formal thought disorder. METHOD: Clinical, neuropsychological, neuropsychiatric, and neuroradiological assessment. RESULTS: A right-handed patient, AJ, presented acutely with a fluent dysphasia. His speech output gradually evolved from undifferentiated jargon, through neologistic jargon, to an intelligible but bizarre form of discourse. Comprehension was relatively well preserved. Radiology revealed an arteriovenous malformation in the left middle, and inferior temporal gyri, with reduced perfusion of the left STG. Six months later his overt dysphasia had recovered, but his speech retained some of its previous characteristics, in particular a tendency to a loose association of ideas which now suggested a disorder of thought. CONCLUSIONS: AJ's case illustrates that comprehension may be unexpectedly preserved in jargon aphasia, and that an overtly linguistic impairment can gradually evolve to an apparent disorder of thought. Indistinguishable formal thought disorders can result from "structural" and "functional" pathology in the dominant temporal lobe. PMID- 17354080 TI - Insight, symptoms and executive functions in schizophrenia. AB - INTRODUCTION: We investigated the relationship of insight with executive functions and symptoms in a group of stabilised inpatients with schizophrenia. METHODS: Executive functions using an extensive battery constituted of several tests as well as psychopathology were assessed in 38 inpatients with a DSM-IV diagnosis of schizophrenia. Insight was assessed with the Scale to assess Unawareness of Mental Disorder (SUMD). RESULTS: A principal component analysis of the insight dimensions revealed a three-factor model which accounted for 98% of the variance. Of particular interest is the finding that a composite factor that accounted for 74% of the variance covered insight dimensions that represent a higher degree of insight (awareness of mental disorder, its social consequences, and attribution of symptoms). Only an association between letter fluency and this composite factor was found, which was weakly mediated by depressive symptoms. A stepwise multiple regression analysis revealed a relationship between antipsychotic dose and awareness of medication effect. No association of illness duration and insight was found. CONCLUSIONS: The findings of partial association between dimensions of insight and measures of executive function supports the growing evidence that insight is a multidimensional phenomenon. Accordingly, they emphasise that in the framework of therapeutic interventions, enhancement of higher levels of insight needs to take into account that patients suffering from schizophrenia have differential impairment in insight dimensions. PMID- 17354081 TI - Specific pattern of attentional changes in impulsive individuals. AB - INTRODUCTION: Although impulsivity is recognised as a major psychopathological feature, its cognitive correlates remain controversial. We evaluated readiness to act induced by a warning signal and attentional engagement in healthy impulsive participants. METHODS: People with high impulsivity scores (HI) and low impulsivity (LI) scores on Barratt's Impulsivity Scale (BIS) were selected among 1250 students from top and bottom deciles. Subjects with personal or family of lifetime Axis I disorders were excluded. Motor preparation was evaluated by a Choice Reaction Time task (CRT) with a randomly presented warning signal with a delay before target of 500 ms or 2000 ms depending on the trial block. Attentional engagement and maintenance of fixation was evaluated by a Cued Target Detection task (CTD) comparing cued (valid, invalid, or double cue) and uncued trials and contrasting fixation offset (gap) or maintenance (overlap) conditions. RESULTS: HI, but not LI participants had a shortened reaction time in the 2000 ms condition of CRT with warning signal, indicating a persistent readiness to act. In contrast to LI, HI showed a decreased reinforcement of attention in the overlap condition of CTD with a hyperreactivity to all types of visual stimuli. CONCLUSIONS: Impulsivity per se appears to be associated with hyperreactivity to warning or cue signals and on inability to maintain attentional fixity. PMID- 17354083 TI - Hallucinatory disorder: preliminary data for a clinical diagnostic proposal. AB - INTRODUCTION: Chronic hallucinatory psychosis is a psychopathological profile reported in French literature but not included in the current Anglo-American psychiatric classifications. We compared a group of patients with a clinical picture related to this syndrome to a group of patients with schizophrenia in order to evaluate the possibility of characterising hallucinatory disorder as a diagnostic entity. METHODS: Nine patients with a clinical profile related to chronic hallucinatory psychosis were compared to a group of nine patients with schizophrenia. All of the patients were clinically evaluated using the measures: SCID-P, GAF, BPRS, PANSS, SAPS, SANS, HRS-A, HRS-D, CDSS, MMSE, and CGI. RESULTS: Analysis of the clinical rating scales characterised schizophrenia as comprising three dimensions (positive, negative, and disorganised symptoms), each of which contributes differently to the psychopathological profile of individual patients. However, the patients with hallucinatory disorder seemed to be mainly characterised by auditory verbal hallucinations, with relative sparing of the other functions typically altered in patients with schizophrenia. CONCLUSIONS: The significant differences between the patients in the two groups seem to support the hypothesis that hallucinatory disorder may be considered as being a separate nosographic entity, in which the clinical picture is dominated by the experience of auditory verbal hallucinations. PMID- 17354084 TI - Social cognition in "pure" delusional disorder. AB - Introduction. Delusional disorders are characterised by monothematic, "encapsulated" and incorrigible false beliefs and misinterpretations of social signals. Due to the rarity of cases with "pure" delusional disorder (DD) in clinical settings most studies of social cognition in delusional patients have focused on patients with paranoid schizophrenia. In the present study we sought to examine emotion recognition, theory of mind abilities, and pragmatic language comprehension in patients with delusional disorder. Methods. Social cognition was assessed in 21 patients recruited over a 3-year period who were diagnosed with delusional disorder, paranoid, erotomanic, or jealous type. In addition to an emotion recognition and theory of mind test battery, we included a novel German Proverb Test, which has been found indicative of subtle theory of mind deficits in schizophrenic patients. Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). Psychopathology was measured using the Positive and Negative Symptoms Scale (PANSS). Patients' task performance was compared to a group of 22 healthy control persons paralleled for verbal intelligence, education, and age. Results. Patients with DD made significantly more perseverative errors in the WCST, they performed more poorly on the theory of mind tasks and the proverb test, but were unimpaired in basic emotion recognition abilities relative to controls. When executive functioning was co-varied out, the group differences in theory of mind disappeared, whereas the greater propensity of patients with DD to interpret proverbs literally remained significant. Conclusions. In "pure" DD the basic social cognitive abilities appear to be preserved. Difficulties in metaphorical speech comprehension and executive functioning could, however, indicate more subtle social cognitive deficits in these patients. PMID- 17354085 TI - Bipolar patients show mood-congruent biases in sensitivity to facial expressions of emotion when exhibiting depressed symptoms, but not when exhibiting manic symptoms. AB - INTRODUCTION: A number of studies have reported mood-congruent biases in processing facial expressions of emotion in depression and mania. Most of them have failed to establish that mood reliably affects relevant more than irrelevant expressions, or that the effect is specifically mood-related rather than due to resource or task difficulty artefacts. The aim was to examine, using appropriate statistical methods, whether depressed mood in bipolar patients decreases and manic mood increases sensitivity to facial expressions of happiness and vice versa for facial expressions of negative emotion. METHODS: Sensitivity to facial expression of six basic emotions in bipolar patients when depressed and when manic was compared to closely matched controls. RESULTS: Mood-related biases in sensitivity to facial expressions of happiness and of negative affect in general operate in persons with bipolar disorder when depressed. There is little evidence of similar biases in persons with bipolar disorder when manic. CONCLUSIONS: These data show a mood-congruent bias in sensitivity to facial expressions in bipolar depressed patients. PMID- 17354086 TI - Probabilistic reasoning in schizophrenia: a comparison of the performance of deluded and nondeluded schizophrenic patients and exploration of possible cognitive underpinnings. AB - INTRODUCTION: A number of studies have suggested that deluded patients show a "jumping to conclusions" reasoning style on probabilistic reasoning tasks. In order to systematically explore the cognitive underpinnings of this task, we compared deluded and nondeluded patients on a number of experimental manipulations to investigate the role of memory and task pragmatics on performance. METHODS: In Study 1, the performance of deluded and nondeluded schizophrenia patient groups was compared to nonpsychiatric controls on a battery of probabilistic reasoning tests. In Study 2, two variants of the standard "beads in jars" task were compared in order to explore the possible role of working memory load on task performance. RESULTS: In Study 1, there were no significant differences between any of the groups on any of the probabilistic reasoning tasks. In Study 2, we found a significant difference between the two schizophrenic groups and the controls, but no difference in performance between deluded and nondeluded patient groups. The deluded group responded fastest in the memory intensive condition. CONCLUSIONS: Deluded and nondeluded schizophrenic patients perform similarly on probabilistic reasoning tasks and only show the "jumping to conclusions" response pattern under some conditions but not under others. Memory demands may influence the appearance of this pattern of responding in schizophrenia. PMID- 17354087 TI - Domain-specific deficits in schizophrenia. AB - INTRODUCTION: Object recognition deficits are well documented in certain neurological disorders (e.g., Alzheimer's disease, herpes simplex encephalitis). Although agnosic problems have been documented in some patients with schizophrenia (Gabrovska et al., 2003), no study has investigated whether such deficits differentially affect specific categories of information (as they sometimes do in neurological cases). METHOD: In Part I of this study, we compared object recognition in 55 patients with chronic schizophrenia and 22 age- and NART IQ-matched healthy controls. In Part II, we present a detailed case study of one patient with schizophrenia (DH) who displays a severe category specific semantic knowledge for living things. RESULTS: Of the patients with schizophrenia, 75% had object recognition below the 5th percentile, and in 11% of cases, a highly specific classical category dissociation emerged (5 cases with nonliving deficit and 1 with living deficit); and two other patients showed strong dissociation for living things. These findings provide convincing evidence of a classical double dissociation across the two categories. In Part II, the in-depth case study of one schizophrenic patient (DH), documented a profound agnosia for living things. While DH displayed intact low level perceptual and spatial ability and could copy drawings, he was severely impaired at naming, picture-name matching, semantic fluency, and could not describe or draw items from memory. CONCLUSIONS: The presence of impaired object recognition in most schizophrenic patients, along with highly selective category specific deficits in a minority, is discussed with reference to similar findings in neurological patients. PMID- 17354088 TI - Selective attention to threatening faces in delusion-prone individuals. AB - INTRODUCTION: Selective attention to threat-related information has been associated with clinical delusions in schizophrenia and nonclinical delusional ideation in healthy individuals. However, it is unclear whether biased attention for threat reflects early engagement effects on selective attention, or later difficulties in disengaging attention from perceived threat. The present study examined which of these processes operate in nonclinical delusion-prone individuals. METHODS: A total of 100 psychologically healthy participants completed the Peters et al. (1999) Delusions Inventory (PDI). Twenty-two scoring in the upper quartile (high-PDI group) and 22 scoring in the lower quartile (low PDI group) completed a modified dot-probe task. Participants detected dot-probes appearing 200, 500, or 1250 ms after an angry-neutral face pair or a happy neutral face pair. RESULTS: High-PDI individuals responded faster to dot-probes presented in the same location as angry compared to happy faces at the short 200 ms stimulus onset asynchrony (SOA), but only when the emotional faces were presented to the left visual field. At the two longer SOAs (500 ms, 1250 ms), the high-PDI group were also faster to respond to dot-probes presented in the same location as angry compared to happy faces and slower to respond to dot-probes presented in different spatial locations to angry (vs. happy) faces. The latter effects were seen whether emotional faces were presented to the left or the right visual field. CONCLUSIONS: Results support the operation of emotion-selective engagement and defective disengagement for threat-related facial expressions (i.e., anger) in delusion-prone individuals. PMID- 17354089 TI - The role of matrix metalloproteinases in the oral environment. AB - This review focuses specifically on matrix metalloproteinases (MMPs) and their role in physiological and pathological extracellular matrix (ECM) remodeling and degradation processes in the oral environment. A group of enzymes capable of degrading almost all ECM proteins, MMPs contribute to both normal and pathological tissue remodeling. The expression of different MMPs may be upregulated in pathological conditions such as inflammation and tumor invasion. The balance between activated MMPs and tissue inhibitors of metalloproteinases (TIMPs) controls the extent of ECM remodeling. Prior to mineralization, MMPs may participate in the organization of enamel and dentin organic matrix, or they may regulate mineralization by controlling the proteoglycan turnover. There is evidence indicating that MMPs could be involved in the etiology of enamel fluorosis and amelogenesis imperfecta. They seem to play a part in dentinal caries progression, since they have a crucial role in dentin collagen breakdown in caries lesions. MMPs have been identified in pulpal and periapical inflammation and are strongly correlated with periodontal diseases, since they are the major players in collagen breakdown during periodontal tissue destruction. The use of MMP inhibitors could help the prevention and treatment of many MMP-related oral diseases. PMID- 17354090 TI - Fracture resistance of different zirconium dioxide three-unit all-ceramic fixed partial dentures. AB - OBJECTIVE: This study evaluated the fracture resistance of different zirconia three-unit posterior all-ceramic fixed partial dentures before and after fatigue loading. MATERIAL AND METHODS: Forty-eight zirconia three-unit posterior all ceramic fixed partial dentures were fabricated using different manufacturing systems and conventionally cemented on human teeth. The restorations were divided according to the system used for manufacturing the frameworks into 3 groups of 16 specimens each (DCS, Procera and Vita CerecInlab). Half of each group was artificially aged through dynamic loading and thermal cycling, whereas the other half was left with no artificial aging. Afterwards, all specimens were tested for fracture resistance using compressive load on the occlusal surface. Non parametric ANOVA using the Kruskal-Wallis and Wilcoxon rank tests was performed to test for differences in fracture resistance values with a global significance level of 0.05. RESULTS: All artificially aged specimens survived with no failures. The median fracture resistance values (before; after artificial aging) were: DCS (1683 N; 1618 N), Procera (1522 N; 1256 N), and Vita CerecInlab (1702 N; 1556 N). No significant differences were found for comparisons between different groups before artificial aging. Artificial aging did not significantly influence the fracture resistance of different groups. After artificial aging, group Procera showed significantly lower fracture resistance than the Vita CerecInlab (p=0.015) and DCS (p=0.038) groups. CONCLUSIONS: All tested restorations have the potential to withstand occlusal forces applied in the posterior region and can therefore represent interesting alternatives for replacing porcelain-fused-to-metal restorations. Further assessment is needed before recommending such restorations in daily practice. PMID- 17354091 TI - Microbiology in toothbrush samples from children exposed to lead in southern Thailand. AB - OBJECTIVE: The purpose of this study was to evaluate the prevalence and level of selected oral bacterial species in association with dental caries in low versus high blood lead (PbB) children. MATERIAL AND METHODS: With an observational cross sectional design, a sample of 292 children aged 6-11 years from two primary schools around a shipyard, known to be an area contaminated with lead, were examined. The number of decayed and filled surfaces on deciduous teeth (dfs) and the number of decayed, missing, and filled surfaces on permanent teeth (DMFS) were recorded. Microbiological plaque samples were taken from each child with a toothbrush. Enumeration of 17 bacterial species was carried out using the checkerboard DNA-DNA hybridization technique. RESULTS: Overall means (SD) of dfs and DMFS were 13.2 (9.5) and 1.3 (2.3), respectively. Prevalence of excessive count (>or=10(6) cells/sample) was 100% for 4 known cariogenic bacteria and over 95% in another 2 species. With Bonferroni correction for type I error adjustment, there was no significant association between the count of each bacterial species and PbB and caries experience. The checkerboard method is sensitive in bacteria detection, but may not be suitable for differentiating caries risk in the endemic population. PMID- 17354092 TI - A seven-year survival analysis of caries onset in primary second molars and permanent first molars in different caries risk groups determined at age two years. AB - OBJECTIVE: To investigate in a group of children (n=183) the effect of possible risk factors registered at the age of 2 years on caries development in 7 years of follow-up, and to study associations between risk groups. MATERIAL AND METHODS: Consumption of candies, use of a nursing bottle at night, use of fluorides, toothbrushing, pacifier sucking, and prolonged breastfeeding (>or=12 months) were recorded at the age of 2 years. The timing of caries onset in different groups was compared by applying a survival analysis method--the survival curves produced separately for selected teeth in different risk groups. RESULTS: The survival curves of caries onset for both primary and permanent molars were consistently lower for children who consumed candies more than once a week, did not brush their teeth daily, were given a nursing bottle at night or a pacifier at age 2 years. The multivariate survival analysis confirmed that consumption of candies and lack of daily toothbrushing were the factors that had the major impact on caries onset in both primary and permanent molars. Prolonged pacifier sucking (>or=2 years) was related only with short duration of breastfeeding. Children with prolonged use of a nursing bottle at night also consumed candies more than once a week, did not brush their teeth regularly, and did not use fluoride tablets. CONCLUSIONS: Consumption of candies and inadequate oral hygiene at age 2 years are important long-term risk factors for caries development in both primary and permanent molars. PMID- 17354093 TI - Timing of developmental stages in permanent mandibular teeth of Finns from birth to age 25. AB - OBJECTIVE: The aim was to provide radiographic data on postnatal development of the 8 mandibular teeth to serve as reference norms in clinical dentistry, forensic dentistry, anthropology, and research. MATERIAL AND METHODS: Developmental stages of teeth were assessed from a total of 2795 radiographs, mostly panoramic, of 1970 Finns (966 M and 1004 F) from birth to age 25. The grading was based on Demirjian's 8 mineralization stages and the crypt stage. RESULTS: Timing of development in individual mandibular teeth is presented in two ways: as age at attainment of each developmental stage and as age of subjects in a developmental stage. Initiation of mineralization was visible in 1st molars at 0.20 years, in central incisors at 0.22 years, lateral incisors at 0.37 years, and canines at 0.56 years of age. Timing was usually earlier in girls than in boys. Differences were greatest in canines, where females were advanced by 1.74 years at the closure of the apex. Root development in 3rd molars showed an opposite trend, where apical closure was 1.19 years earlier in men. In 3rd molars, age at apical closure in females was 21.50 years, among the highest reported. In general, the early developmental stages had the shortest duration and the last stages the longest. CONCLUSION: Timing of postnatal development of individual mandibular teeth in Finns resembled developmental schedules reported for other Caucasian population groups. Any differences were mostly small and inconsequential. PMID- 17354094 TI - Pilot evaluation of resin composite cement adhesion to zirconia using a novel silane system. AB - OBJECTIVE: In this study, we evaluated the effect of two silane coupling agents and their blends with a cross-linker silane on the bond strength of a dimethacrylate-based resin composite cement to surface-conditioned zirconia. MATERIAL AND METHODS: A total of 40 planar zirconia specimens were used for 8 test groups. After alumina particle abrasion, followed by tribochemical silica coating, the specimens were randomly assigned to four silanizations: with 1.0 vol% 3-methacryloyloxypropyltrimethoxysilane or 1.0 vol% 3 mercaptopropyltrimethoxysilane or their blends with 1.0 vol% 1,2-bis (triethoxysilyl)ethane (all in ethanol/water). The resin composite (RelyX ARC, 3M ESPE) stubs (n=10/group) were light-polymerized onto zirconia specimens. Four test groups were tested without water storage and 4 thermo-cycled at 6000 cycles (5+/-1 degrees C to 55+/-1 degrees C), with a dwelling time of 30 s. The shear bond strength of the cement stubs to zirconia was measured using a universal testing machine at a constant cross-head speed of 1 mm/min. Scanning electron microscopy was employed for imaging the zirconia surface after conditioning and testing. Failure mode was evaluated visually. A surface chemical analysis was carried out with the EDXA system. RESULTS: The highest shear bond strength was 21.9+/-8.7 MPa, obtained with a blend of 3-mercaptopropyltrimethoxysilane and 1,2 bis-(triethoxysilyl)ethane (dry storage), and 16.0+/-1.5 MPa, with 3 methacryloyloxypropyltrimethoxysilane (thermo-cycled). Thermo-cycling decreased the bond strengths significantly (ANOVA, p<0.01), and the silanes differed significantly (p<0.005). Some specimens suffered from spontaneous debonding during thermo-cycling. CONCLUSIONS: The luting cement adhesion might be promoted to silica-coated zirconia with 1.0 vol% 3-methacryloyloxypropyltrimethoxysilane and with a blend of 1.0 vol% 3-mercaptopropyltrimethoxysilane and 1.0 vol% 1,2 bis-(triethoxysilyl)ethane. PMID- 17354095 TI - Microbiological effect of the use of an ultrasonic device and iodine irrigation in patients with severe chronic periodontal disease: a randomized controlled clinical study. AB - OBJECTIVE: Instrumentation of the subgingival area is aimed at removing as much as possible of the bacterial biofilm and subgingival calculus. Since mechanical root debridement is a technically demanding procedure, antiseptics and antibiotics delivered either locally or systemically have been used as adjunct to scaling and root-planning procedures in order to control the subgingival biofilm and thereby enhance the treatment outcome. Our aim was to study the microbiological effect of ultrasonic debridement with or without povidone-iodine (PVP-iodine) in the treatment of severe chronic periodontitis. MATERIAL AND METHODS: Twenty patients were recruited to the study. Each test site and the related quadrant were randomly assigned to one of four different treatment modalities: ultrasonic scaling+subgingival irrigation with 0.5% PVP-iodine for 5 min/tooth, ultrasonic scaling+subgingival irrigation with sterile saline solution for 5 min/tooth, subgingival irrigation with sterile saline solution for 5 min/tooth and subgingival irrigation with 0.5% PVP-iodine for 5 min/tooth. The individuals were followed longitudinally for 6 months. RESULTS: The present study showed that non-surgical periodontal therapy with the use of an ultrasonic device was effective in reducing the analyzed putative periodontal bacteria. No statistically significant difference between ultrasonic+saline and ultrasonic+PVP iodine was found. CONCLUSIONS: Ultrasonic debridement reduced the periodontal markers in patients with severe chronic periodontitis. The reduction was selective. A concentration of 0.5% PVP-iodine did not add any anti microbiological effect compared to ultrasonic debridement alone. PMID- 17354096 TI - In vitro quantification of smooth surface caries with DIAGNOdent and the DIAGNOdent pen. AB - OBJECTIVE: A new generation of the laser fluorescence device, DIAGNOdent, for caries detection and quantification has been introduced recently. It is the DIAGNOdent pen. The aim of this study was to compare the validity and reliability of both laser-based devices, DIAGNOdent and the DIAGNOdent pen, in quantifying smooth surface caries. MATERIAL AND METHODS: The material comprised a sample of 52 premolar teeth extracted on orthodontic indication. The teeth were visually sound or had various stages of non-cavitated carious lesions on smooth surfaces. All teeth were photographed and measured with both DIAGNOdent and the DIAGNOdent pen by two examiners independently. The teeth were then sectioned into 300-microm slices and analysed under a microscope for verification of lesion depth. Histopathological analyses were performed by two observers to assess lesion depth, which was classified into five categories ranging from sound to dentinal caries. Reliability and validity of the two devices were evaluated in terms of intra-class coefficients and Spearman rank correlation coefficient, respectively. The relation between measurements performed by DIAGNOdent and the DIAGNOdent pen was analyzed using Pearson's correlation coefficient. RESULTS: Both DIAGNOdent and the DIAGNOdent pen had excellent intra-observer agreement and acceptable inter-observer agreement. The correlation with histology for DIAGNOdent and the DIAGNOdent pen ranged between 0.47 and 0.57, although the correlation between DIAGNOdent and the DIAGNOdent pen was high. CONCLUSIONS: In this in vitro study, the new laser fluorescence device, the DIAGNOdent pen, showed similar reliability and validity at quantification of smooth surface caries compared to the conventional DIAGNOdent device. Agreement between DIAGNOdent and the DIAGNOdent pen was excellent. PMID- 17354097 TI - Vaccines targeting tumor vasculature: a new approach for cancer immunotherapy. PMID- 17354098 TI - UC blood hematopoietic stem cells and therapeutic angiogenesis. AB - Studies suggest that mobilized hematopoietic stem cells (HSC) are recruited to ischemic tissue and stimulate angiogenesis. Critical observations in pre-clinical studies have identified an augmentation of endogenous microvascular collateralization that is beyond that directly attributable to anatomic incorporation and differentiation of infused human cells into the vascular endothelium. Evidence links age-associated reductions in the levels of circulating marrow-derived HSC characterized by expression of early HSC markers CD133 and CD34, with the occurrence of cardiovascular events and associated death. Utilizing the patient's own HSC to augment angiogenesis has several disadvantages, including reduced function of these cells and logistical issues related to cell collection from individual patients. Thus an available source of allogeneic HSC such as UC blood for cellular therapy may be optimal. PMID- 17354099 TI - Short-term endothelial progenitor cell colonies are composed of monocytes and do not acquire endothelial markers. AB - BACKGROUND: The aim of this study was to identify circulating endothelial progenitor cells (EPC) with colony-forming capacity and compare them with the monocytic-macrophage lineage. METHODS: Forty-two healthy donors were analyzed. EPC were cultured with VEGF and b-FGF. Sequential studies were performed on days +7 (colonies) +21 and +35. Monocytic cells were cultured using the same conditions as EPC until day +21 or alternatively by adding IGF. RESULTS: The number of EPC colonies was higher in BM than in mobilized or steady-state PB. Using EPC medium, monocytic cells formed cord-like structures but no colonies. However, colonies grew when IGF was added to the medium. By immunocytochemistry, colonies showed CD45, CD31 and lysozyme but no vWF. Colonies were CD4+, CD13+dim, CD14+, CD15++, CD16-/+dim, CD31+dim, CD33+dim, CD45+, CD105-/+dim, lysozyme+ and VE-cadherin+, and constantly negative for CD34, CD133 and KDR, when flow cytometry was used. The immunophenotype of pre-cultured and cultured monocytes was similar to that described for EPC. DISCUSSION: Our results suggest that the so-called 'EPC' obtained at 7 days of culture belong to the monocyte-macrophage lineage, as they share immunophenotypic and molecular features. PMID- 17354100 TI - Good manufacturing practice-compliant validation and preparation of BM cells for the therapy of acute myocardial infarction. AB - BACKGROUND: Intracoronary application of BM-derived cells for the treatment of acute myocardial infarction (AMI) is currently being studied intensively. Simultaneously, strict legal requirements surround the production of cells for clinical studies. Thus good manufacturing practice (GMP)-compliant collection and preparation of BM for patients with AMI was established by the Cytonet group. METHODS: As well as fulfillment of standard GMP requirements, including a manufacturing license, validation of the preparation process and the final product was performed. Whole blood (n=6) and BM (n=3) validation samples were processed under GMP conditions by gelafundin or hydroxyethylstarch sedimentation in order to reduce erythrocytes/platelets and volume and to achieve specifications defined in advance. Special attention was paid to the free potassium (<6 mmol/L), some rheologically relevant cellular characteristics (hematocrit <0.45, platelets <450 x 10(6)/mL) and the sterility of the final product. RESULTS: The data were reviewed and GMP compliance was confirmed by the German authorities (Paul-Ehrlich Institute). Forty-five BM cell preparations for clinical use were carried out following the validated methodology and standards. Additionally three selections of CD34+ BM cells for infusion were performed. All specification limits were met. Discussion In conclusion, preparation of BM cells for intracoronary application is feasible under GMP conditions. As the results of sterility testing may not be available at the time of intracoronary application, the highest possible standards to avoid bacterial and other contaminations have to be applied. The increased expense of the GMP-compliant process can be justified by higher safety for patients and better control of the final product. PMID- 17354101 TI - BM stem cell transplantation rescues pathophysiologic features of aged dystrophic mdx muscle. AB - BACKGROUND: The value of transplantation of BM stem cells in aged (12-month-old) mdx was evaluated because it is thought to be a more ideal model for studying the praxiology of Duchenne muscular dystrophy (DMD). The possible mechanisms of stem cell differentiation were then discussed. METHODS: BM was isolated from 8-10-week old male C57 BL/10 mice. After injecting BM cells into 12-month-old female mdx mice through the tail vein, the expression of dystrophin and MyoD was detected at different time points by immunofluorescence staining, RT-PCR and Western blot. RESULTS: The C57 male mice donor-specific and Y-chromosome-specific sequence could be detected in all female aged mdx mice, implying the success of the transplantation. Expression of dystrophin and MyoD was detected and increased over time. DISCUSSION: BM cells were recruited to the muscle and partially restored specific pathophysiologic features of the dystrophic muscle in aged mdx mice. Muscle differentiation of BM cells recapitulated embryonic myogenesis. PMID- 17354102 TI - Application of microarray technology for microbial diagnosis in stem cell cultures: a review. AB - Stem cell lines used for cell therapy and regenerative medicine programs could be contaminated by several types of microorganism, such as bacteria, fungi, yeasts, viruses and prion particles. The presence of these pathogens makes the stem cell cultures unsuitable for transplant in humans. At the moment, tests for detecting these kinds of pathogens are carried out by means of standardized diagnosis procedures, in order to avoid the possibility of transmitting infectious diseases to the recipients of stem cell products. Some of the methods that can be included in a microbiologic control program are culture-based methods for sterility assessment, molecular techniques (PCR, RT-PCR), Ag detection and electron microscopy. However, new technologies based on DNA microarrays and protein arrays could also be applied for microbial diagnosis in stem cell lines in order to improve the microorganism detection. In this review, we summarize the main features concerning microarray methodology, the advantages and disadvantages regarding microbial diagnosis for stem cell cultures and possible future application in stem cell research centers in the microbiology field. PMID- 17354103 TI - High-yield expression, purification and characterization of tumor-targeted IFN alpha2a. AB - BACKGROUND: IFN-alpha has been shown to be effective against hematologic malignancies. However, it is ineffective against most solid tumors and has not been satisfactory because of its toxicity. METHODS: The NGR (Asn-Gly-Arg) peptide is a tumor-homing peptide. In order to increase the anti-tumor activity of IFN alpha2a and lower the dose, we coupled a cyclic NGR peptide with the C terminus of IFN-alpha2a (named IFN-alpha2a-NGR). RESULTS: The fusion protein was expressed in E. coli and purified by ion-exchange chromatography. The purity of IFN-alpha2a NGR was >98% and the final purification yield of IFN-alpha2a-NGR was approximately 18 mg/L. The anti-tumor efficacy and the binding ability of IFN alpha2a-NGR with tumor vasculature were investigated in vitro and in vivo. DISCUSSION: Our study has demonstrated that the anti-tumor efficacy of IFN alpha2a-NGR is significantly increased in comparison with IFN-alpha2a, and IFN alpha2a-NGR could selectively target tumor vessels. These data indicate that the tumor-homing peptide (NGR) can enhance the therapeutic efficacy of IFN-alpha2a against tumors. PMID- 17354104 TI - Impact of culture conditions on the proliferative lifespan of human T cells in vitro. AB - BACKGROUND: In human T cells, telomerase is transiently expressed upon activation and stimulation and, as shown previously, telomerase levels are able to control the lifespan of T cells. To improve T-cell expansion it is of critical importance to understand the effects of culture parameters on telomerase activity and lifespan. METHODS: We investigated the influence of culture condition (FCS, human AB serum and autologous serum) and stimulation (PHA/feeder cells, anti-CD3/CD28 beads) on the lifespan, clonogenicity (number of positive wells), cell cycle, telomerase activity and telomere length of T cells in vitro. RESULTS: The proliferative lifespan of T cells expanded with PHA/feeder cells and autologous serum from different donors was doubled compared with stimulation with PHA/feeder cells and AB serum. No or only a small difference was found for T cells expanded with anti-CD3/CD28 beads and autologous or AB serum. The use of autologous serum also increased the clonogenicity to about three-fold compared with the use of AB serum or FCS, without any signs of differences in the fractions of cycling cells. Interestingly, T cells cultured with autologous serum exhibited a significantly higher telomerase activity at day 6 after stimulation and a reduced decline of telomerase activity compared with cultures with AB serum. DISCUSSION: The use of autologous serum combined with PHA stimulation and feeder cells remarkably extends the proliferative lifespan and clonogenicity and increases the telomerase activity of human T cells in vitro. This might be useful for applications where large numbers of specific T cells are required. PMID- 17354105 TI - Peripheral endothelial progenitor cells (CD133 +) for therapeutic vasculogenesis in a patient with critical limb ischemia. One year follow-up. AB - We present a patient with critical limb ischemia who was successfully treated with the injection of autologous peripheral blood (PB) CD133+ purified stem cells (SC) into the gastrocnemius muscle. No serious adverse events related to G-CSF administration, mononuclear cells harvest or CD133+ SC administration was observed. After 17 months of follow-up, our patient has experienced limb salvage, symptomatic relief and functional improvement. Moreover, we have observed the appearance of flow in the right posterior tibial artery that was absent before the procedure. To our knowledge, this is the first case of critical limb ischemia treated with PB CD133+ SC. PMID- 17354106 TI - Molecular mechanisms of pancreatic cancer and potential targets of treatment. PMID- 17354107 TI - pH 4.0. PMID- 17354108 TI - Omeprazole reduces the response to capsaicin but not to methacholine in asthmatic patients with proximal reflux. AB - OBJECTIVE: To study the relationships between airway responsiveness to methacholine and capsaicin, proximal or distal reflux and the effects of short term acid inhibition. MATERIAL AND METHODS: Twenty-nine asthmatics, not taking steroids regularly, underwent respiratory symptom measurements, 24-h dual-probe pH monitoring, and challenges with methacholine and capsaicin. Challenges and symptom measurements were repeated after 12 days' omeprazole treatment (20 mg b.i.d.). The results (median and range) were expressed as PD20 methacholine (mg) and PD5 capsaicin (dose causing five coughs, nmol). RESULTS: Seventeen patients presented pathological reflux in the distal esophagus, and 17 in the proximal esophagus. At baseline no correlation was found between PD20 or PD5 and reflux. Treatment with omeprazole did not change bronchial responsiveness to methacholine (basal: 0.16 mg, 0.02-1.27; omeprazole: 0.15 mg, 0.02-1.60); omeprazole decreased the tussive response to capsaicin (basal: 0.08 nmol, 0.08-2.46; omeprazole: 0.61 nmol, 0.08-9.84, p<0.001) only in patients with pathological reflux. The decrease was positively correlated with proximal acid exposure (r2=0.70, p<0.001). Omeprazole reduced asthma symptoms in patients with proximal reflux, cough in those with proximal or distal reflux. CONCLUSIONS: In asthmatics, inhibition of gastric acid secretion does not influence bronchial hyperresponsiveness but decreases tussive sensitivity and this effect is related to proximal reflux. PMID- 17354109 TI - Modelling a population with Barrett's oesophagus from oesophageal adenocarcinoma incidence data. AB - OBJECTIVE: A recent study of adenocarcinoma of the oesophagus (ACO) incidence rates in Denmark showed a steep fall in the over-80 population, interpreted as the result of a decline in the prevalence of Barrett's oesophagus (BO) in this age group, for which three hypotheses were advanced: the specific mortality from ACO and, superimposed, either excess mortality from causes of death unrelated to ACO or a birth cohort effect. The aim of this study was to create models estimating the BO population fitting each of these three hypotheses, in order to select the most plausible hypothesis and to gain insight into the Danish BO population. MATERIAL AND METHODS: Models were designed for these three hypotheses, conforming to the generally accepted 0.4-0.5% annual ACO incidence in BO patients. These models employed expectation-maximization (EM) algorithms, Danish life tables and the observed ACO incidence rates. The models enabled the estimation of a BO population for each hypothesis. RESULTS: After testing against set criteria, the most plausible model was found to be that describing a birth cohort effect which predicted a +/-5% annual rise in the prevalence of BO and, consequently, in the incidence rate of ACO in Denmark. This prediction was borne out over the subsequent decade. CONCLUSIONS: This rising ACO incidence rate is likely to continue into the foreseeable future. The use of EM algorithms enabled a first estimate of the BO population at risk of ACO, although, owing to the limitations imposed by the models, the age- and gender-specific ACO risk for the entire Danish BO population could not as yet be ascertained. PMID- 17354110 TI - Clinical practice and evidence in endoscopic treatment of bleeding peptic gastroduodenal ulcer. AB - OBJECTIVE: To investigate treatment practice in non-variceal upper gastrointestinal bleeding (NVUGIB) caused by gastroduodenal ulcer and how it adheres to the best evidence as documented in randomized studies and meta analyses. MATERIAL AND METHODS: The literature was surveyed to identify appropriate practices, and a structured multiple choice questionnaire developed and mailed to all departments in Denmark treating UGIB. RESULTS: All 42 departments responded. All had therapeutic gastroscopes and equipment necessary for endoscopic haemostasis; 90% of departments had written guidelines. Adjuvant pharmacologic treatment included tranexamic acid in 38%. Proton-pump inhibitors (PPIs) were used by all departments, with 29% starting prior to endoscopic treatment. Eight departments (19%) used continuous PPI infusion, three of them starting with a bolus dose. In 50% of departments an anaesthesiologist was always present regardless of whether endotracheal intubation (routinely used by 10%) was used or not. Ten percent did not treat Forrest IIa and IIb ulcers, while IIc ulcers were treated by 36%. In 10% of departments clots were never removed, while in 2/3 attempts were made to remove resistant clots by mechanic means. Seven departments (17%) used monotherapy with epinephrine, while 59% always used dual therapy; 19% injected less than 10 ml. In rebleeding, 92% attempted endoscopic treatment before surgery, and used epinephrine in 79% of cases, while the remainder used epinephrine or polidocanol at the discretion of the endoscopist. Two out of three departments used high-dependency or intensive-care units for surveillance. Seventeen percent applied scheduled second-look gastroscopy. CONCLUSIONS: Practice is variable, even in areas with established evidence based on randomized controlled studies, such as dosage and way of administration and duration of PPI treatment, injection treatment used as monotherapy and the volume used, including ulcers with clots for treatment, and the use of scheduled second look endoscopy. Since the rebleeding rate has remained unchanged for decades, and rebleeding implies increased surgery and mortality rates, appropriate practices must be promoted in order to improve results. Development and implementation of national guidelines may facilitate the process. PMID- 17354111 TI - Persistence of Helicobacter pylori infection in patients with peptic ulcer perforation. AB - OBJECTIVE: In patients with perforated peptic ulcer (PPU) the convergence between the high eradication rate of Helicobacter pylori infection and low rates of ulcer relapse after treatment has been associated with reinfection by non-virulent strains. The objective of this study was to evaluate the persistence of infection by virulent H. pylori strains and ulcer recurrence in 33 patients with PPU one year after surgery and antimicrobial treatment. MATERIAL AND METHODS: The histological evaluation and molecular detection of H. pylori cagA and ureA genes, vacA allelic types and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses of the glmM gene products from antral mucosa specimens were performed initially, 2-5 months and 1 year after therapy. RESULTS: The density of H. pylori colonization was temporarily decreased (p<0.05) 2-5 months after therapy. After one year, complete eradication was achieved in only 7 patients (23%) at histological examination and recurrent ulcers were found in 3/33 (9%) patients. The vacA s1a allelic type of cagA-positive strains persisted in 19/33 (58%) PPU patients with identical PCR-RFLP fingerprints in 8/9 (89%) of the patients. CONCLUSIONS: In PPU patients with a low eradication rate of H. pylori infection after surgical and antimicrobial treatment, the frequent recrudescence of the infection is mostly caused by the persisting virulent strains of the cagA and vacA s1a subtypes. In the 1-year follow-up period the recurrent ulceration can be postponed just by the lowered colonization density of H. pylori after eradicative therapy. PMID- 17354112 TI - Comparison of two invasive diagnostic tests for Helicobacter pylori after antimicrobial therapy. AB - OBJECTIVE: To compare the accuracy of two invasive tests, the rapid urease test and histology, one month after antimicrobial treatment of Helicobacter pylori. MATERIAL AND METHODS: In the present study the rapid urease test was compared with histology in a group of 232 patients who fulfilled the Maastricht criteria for eradication of H. pylori infection. All patients had one week of triple therapy which included omeprazole b.i.d. and two of three antibiotics (metronidazole, clarithromycin and amoxicillin) b.i.d. One month after antimicrobial therapy, all the patients underwent upper gastrointestinal endoscopy. Two biopsy samples were taken from the antrum and corpus for each test. We used the office rapid urease test, which was previously evaluated, and histology with Giemsa stain. RESULTS: Concordance between both methods was 94% for antrum biopsies, 97% for corpus biopsies and 96% for pooled data. Kappa values were 0.81 for antrum (95% CI: 0.77-0.85%), 0.87 for corpus (95% CI: 0.83 0.91%) and 0.84 for pooled data (95% CI: 0.80-0.88%). Specificity of the rapid urease test is very high (over 98%), sensitivity is lower, but can be improved, if biopsy specimens are taken from both the corpus and the antrum (to 83.6%). CONCLUSIONS: The rapid urease test with two biopsies from the antrum and corpus of the stomach is a reliable diagnostic method for evaluation of the success of H. pylori eradication one month after antimicrobial therapy. PMID- 17354113 TI - Treatment inferred disease severity in Crohn's disease: evidence for a European gradient of disease course. AB - OBJECTIVE: Geographic differences in disease course of Crohn's disease (CD) might possibly be related to differences in genetic and environmental factors encountered in different parts of the world. The aim of this study was to assess differences in treatment regimens within a European cohort of CD patients as a reflection of disease course, and to identify associated phenotypic risk factors at diagnosis. MATERIAL AND METHODS: A prospective European population-based inception cohort of 380 CD patients was studied. The patients were classified for phenotype according to the Vienna classification. Differences between Northern and Southern European centres in treatment over the first 10 years of disease were analysed using a competing risks survival analysis method. RESULTS: Patients in the North were more likely to have had surgery (p<0.01), whereas patients in the South were more likely to have been treated medically (p<0.01). Phenotype at diagnosis was not predictive of differences in treatment regimens between North and South. CONCLUSIONS: In this study, a difference in management of CD was observed between Northern and Southern European centres. This suggests that there may be a North-South disease severity gradient across Europe. Phenotypic differences between patients in the North and South did not explain this observed difference. PMID- 17354114 TI - Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations. AB - OBJECTIVE: The inhibitory proteins, IkappaBs, regulate the activity of nuclear factor kappa-beta (NF-kappaB), which is implicated in tumorigenesis by regulating expression of a variety of genes involved in cellular transformation, proliferation, invasion, angiogenesis and metastasis. Variants in the genes encoding IkappaBs may be involved in cancer development through the activation of NF-kappaB. The objective of this study was to investigate the susceptibility of an A to G variation (rs696) in the 3' UTR of NFKBIA (encoding IkappaBalpha) to colorectal cancer (CRC) and the association of this polymorphism with clinicopathologic variables in CRC patients. MATERIAL AND METHODS: A case-control study was carried out on a Swedish (155 CRCs, 438 controls) and a Chinese population (199 CRCs, 577 controls). The genotype of NFKBIA was determined by PCR restriction fragment length polymorphism. RESULTS: The frequency of the AG genotype was increased in the Chinese patients >or=50 years of age compared with the Chinese controls (odds ratio (OR)=3.06, 95% confidence interval (CI)=1.55 6.02, p=0.001), even when adjusted for age (OR=3.20, 95% CI=1.61-6.38, p=0.001). The GG genotype of NFKBIA was related to a poorer survival rate in the Swedish patients, independent of gender, age, tumour location, Dukes' stage and differentiation (hazard ratio = 3.10, 95% Cl=1.28-7.60, p=0.01). CONCLUSIONS: Chinese individuals >or=50 years of age carrying the AG genotype of NFKBIA may be at an increased risk of developing CRC, and the GG genotype of NFKBIA may be considered as a prognostic factor for Swedish CRC patients. PMID- 17354115 TI - Expected and unexpected gallstones in primary care. AB - OBJECTIVE: The aim of this prospective cohort study was to assess the differences in signs and symptoms of primary-care patients with expected and those with unexpected gallstones referred for upper abdominal ultrasound (US). MATERIAL AND METHODS: A total of 430 patients were referred by 76 general practitioners (GPs) for abdominal US to one of the three participating hospitals in The Netherlands. All GPs were asked to complete a standardized questionnaire before and after abdominal US. Patients with expected gallstones had a clinical suspicion of gallstones and cholelithiasis on abdominal US, patients with unexpected gallstones had cholelithiasis without a clinical suspicion of gallstones. RESULTS: Almost 50% of the patients were referred for abdominal US because of a clinical suspicion of gallstones. Cholelithiasis was detected by US in 29% of the patients with, and 11% of those without a clinical suspicion of gallstones. In patients suspected of gallstones, those with cholelithiasis detected by US were significantly less often of male gender, they had no prior cholecystectomies, were more likely to have colicky pain, and were more frequently referred to a medical specialist after US. Patients with unexpected gallstones were more often male, had fewer complaints of upper abdominal and colicky pain, and were less frequently referred to a medical specialist after US, in comparison with patients with expected gallstones. CONCLUSIONS: Gallstones were detected by upper abdominal US in 29% of the patients with, and 11% of those without a clinical suspicion of gallstones. This study showed marked differences in signs and symptoms of patients suspected of gallstones with and without cholelithiasis detected on abdominal US, and in patients with expected and unexpected gallstones. PMID- 17354116 TI - Endothelium-derived hyperpolarization factor (EDHF) is up-regulated in a pig model of acute liver failure. AB - BACKGROUND: Acute liver failure (ALF) is hemodynamically characterized by hyperdynamic circulation, but the pathophysiologic mechanisms underlying these disturbances are not known. The purposes of the present experiments were: to study systemic and peripheral hemodynamics in vivo, to measure changes in vascular reactivity in vitro, and to determine the role of endothelium-dependent vasodilator pathways in a well-validated porcine model of ALF. METHODS: Landrace pigs (24-29 kg) were allocated to sham operation (n=8) or ALF induced by hepatic devascularization (n=9). Systemic and regional hemodynamics were monitored. Femoral artery rings were prepared for isometric tension recordings 8 h after ALF induction. Contractile responses to phenylephrine were assessed in ring segments of endothelium-intact femoral arteries in the absence or presence of inhibitors of endothelium-derived hyperpolarizing factor, nitric oxide synthase, cyclooxygenase and heme oxygenase pathways. RESULTS: Pigs with ALF developed a hyperdynamic circulation. Cardiac index increased (PGT<0.001), while mean arterial pressure (PGT=0.012) and systemic vascular resistance decreased (PGT<0.001) in this group. Femoral artery blood flow decreased in controls, while it remained unchanged in ALF (PGT=0.010). Accordingly, vascular resistance across the hind leg was significantly decreased (PGT<0.001) in ALF. The combination of Ca2+-activated potassium channel inhibitors charybdotoxin and apamin, which block the release of endothelium-derived hyperpolarizing factor, increased the contraction force (ANOVA, PGT=0.05) and Emax (P=0.01) to phenylephrine in ALF. In contrast, inhibitors of nitric oxide synthase, cyclooxygenase and heme oxygenase pathways did not increase isometric contraction force. CONCLUSIONS: Endothelium dependent hyperpolarization of vascular smooth muscle contributes to the development of hyperdynamic circulation in ALF. PMID- 17354117 TI - Improvement in the routine diagnostic assessment of the liver by high-resolution sonography: an analysis of 999 cases. AB - OBJECTIVE: High-frequency ultrasound transducers have been helpful in certain settings of transabdominal ultrasound examination, and their role in the evaluation of the liver surface in patients with cirrhosis is well documented. However, their value in the routine assessment of the liver has not yet been analysed systematically. The aim of this pilot study was to clarify whether the additional use of high-frequency ultrasound as compared to the standard 3.5 MHz transducer is of any benefit. MATERIAL AND METHODS: A total of 999 patients from a tertiary care medical centre were examined with a wideband 3.5 MHz- and a high frequency transducer (band width 4.5 to 10 MHz) with tissue harmonic imaging using one of two high-end ultrasound machines (Siemens Sonoline Elegra or Hitachi EUB-8500). Findings on hepatic pathologies were collected on a standardized documentation sheet and were evaluated using descriptive statistics. RESULTS: In all, 948 patients showed a plain liver surface when the 3.5 MHz transducer was used, whereas this was only true for 862 patients examined with the high frequency probe. Using the 7.5 MHz probe, the structure of the liver parenchyma appeared to be homogeneous (n=800; 80.1%) less often than when the 3.5 MHz probe (n=822; 82.3%) was used. More cases of liver cirrhosis were suspected with the high-frequency probe (n=66; 6.6% as compared with n=49; 4.9%). In 85 patients (8.5%) new hepatic pathologies were described which had not been detected with the 3.5 MHz probe. The examiners judged the high-frequency examination to be helpful in 284 cases. The time needed for the additional examination ranged between 0.5 and 10 min (mean: 2.2 min). CONCLUSIONS: This study demonstrates that the additional use of a high-frequency transducer during routine abdominal examinations reveals new hepatic pathologies in a significant proportion of examined patients, without substantial prolongation of the overall examination period. PMID- 17354118 TI - A simple clinical score predicts high risk for upper gastrointestinal hemorrhages from varices in patients with chronic liver disease. AB - OBJECTIVE: Upper gastrointestinal (GI) bleeding from esophageal or gastric fundus varices is a common complication of portal hypertension in liver cirrhosis and carries a high mortality rate of 20-35%. Stratifying high-risk patients for variceal bleeding is mainly based on endoscopic scoring. The purpose of this study was to develop a simple clinical score to assess the bleeding risk. MATERIAL AND METHODS: A total of 111 patients with chronic liver diseases were included during evaluation for potential liver transplantation and were followed for 6 years. Findings at study entry were analyzed for their value in predicting hemorrhages. RESULTS: Twenty-four patients (22%) developed upper GI hemorrhages from varices during the follow-up period. Common characteristics at study entry of patients with future bleedings included viral hepatitis or alcoholic etiology, advanced-stage cirrhosis, decreased liver function, impaired hemostasis and endoscopic presence of varices. These parameters were also independent predictors of bleedings. A four-item Bleeding Risk Score, including cholinesterase <2.25 kU/l, international normalized ratio (INR) >1.2, viral or alcoholic etiology and presence of varices, was used to identify patients at high (>2 points) or low (38 degrees C was seen after all but four embolizations, and urinary tract infections were diagnosed after eight embolizations. CONCLUSION: Selective hepatic artery embolization with Embosphere particles is a safe treatment for patients with metastatic neuroendocrine tumors and may lead to partial radiological response as well as symptomatic improvement of disabling endocrine symptoms. PMID- 17354140 TI - Thyroid arterial embolization to treat Graves' disease. AB - PURPOSE: To prospectively investigate the effect of thyroid arterial embolization on hyperthyroid Graves' disease in selected patients. MATERIAL AND METHODS: Twenty-eight patients with hyperthyroidism caused by Graves' disease were enrolled to undergo thyroid arterial embolization and followed up for 12-22 months. Twenty-two patients had three thyroid arteries embolized and six patients two arteries. Serum thyroid hormone, thyroid-stimulating hormone (TSH), and autoimmune function were tested before and after embolization in all patients. RESULTS: Of 28 patients, 22 (78.6%) became euthyroid, five improved (17.8%), and one had temporary improvement followed by recurrence (3.6%). No serious complications occurred. Compared with the pre-embolization values, serum concentrations of thyroid hormone increased temporarily on day 3 post embolization, dropped substantially after 1 and 2 months, and returned to nearly normal at 6 and 12 months post-embolization. TSH dropped on day 3, increased after 1 and 2 months, and returned to normal after 6 and 12 months. Thyroid antibodies TGAb and TMAb declined on day 3 to normal range, rose after 1 month, dropped to normal again after 2 months, and were slightly increased at 6 and 12 months follow-up. CONCLUSION: Thyroid arterial embolization may be an effective approach for patients with hyperthyroidism caused by Graves' disease. PMID- 17354141 TI - The influence of magnetic resonance imaging findings of degenerative disease on dual-energy X-ray absorptiometry measurements in middle-aged men. AB - PURPOSE: To examine degenerative features based on magnetic resonance imaging (MRI) measurements at the lumbar spine in relation to dual-energy X-ray absorptiometry (DXA), and to investigate whether bone mineral density (BMD) is reflected in the substitution of bone trabecular structure by fat at the vertebral body level indicated by MRI T1 relaxation time, endplate concavity, and hypertrophic (osteophytes and endplate sclerosis) MRI findings. MATERIAL AND METHODS: The sample for this cross-sectional study was composed of 102 subjects, 35-70 years old, from a population-based cohort. Data collection included DXA in the anterior-posterior projection at the L1-L4 vertebrae and right femoral neck, and MRI of the lumbar spine in the midsagittal plane. RESULTS: Age, vertebral signal intensity, osteophytes, and endplate concavity collectively explained 20% of the variance in spine BMD. CONCLUSION: The study findings suggest that degenerative findings based on MRI measurements at the lumbar spine have an influence on bone assessment using DXA. Therefore, an overall bone assessment such as DXA might not offer an accurate measure of BMD. PMID- 17354142 TI - Quantitative magnetic resonance techniques in the evaluation of intracranial tuberculomas. AB - PURPOSE: To evaluate intracranial tuberculomas using quantitative magnetic resonance (MR) techniques such as T2 relaxometry, magnetization transfer (MT), and diffusion-weighted imaging (DWI). MATERIAL AND METHODS: Thirty-three patients with intracranial tuberculomas (histologically confirmed in 22) were evaluated using proton density/T2-weighted, T1-weighted (with and without MT), and echo planar diffusion-weighted imaging sequences. T2 relaxation times, MT ratios (MTR), and apparent diffusion coefficient (ADC) values were calculated from the center of the lesion, the periphery, perilesional edema, and contralateral normal white matter. The mean and standard deviation values of each variable were calculated and correlated using Pearson's test (P = 0.05). RESULTS: The measured mean values of T2 relaxation time, MTR, and ADC in the center of lesions were 155.5 ms, 14.1, and 1.27 x 10(-3) mm(2)/s, respectively, compared to 117 ms, 23.72, and 0.74 x 10(-3) mm(2)/s in normal white matter, and a T2 relaxation time of 187.45 ms in normal gray matter. Significant inverse correlations were noted between T2 relaxation values and MTR (P<0.001) and between MTR and ADC (P = 0.046). Significant positive correlation was seen between T2 relaxation and ADC values (P = 0.03). CONCLUSION: Intracranial tuberculomas are characterized by relatively short T2 relaxation times (compared to normal gray matter), decreased MTR, and mostly no restriction of diffusion. A combination of these quantitative parameters could be of help in the noninvasive diagnosis of tuberculomas. PMID- 17354143 TI - Limited cone-beam computed tomography imaging of the middle ear: a comparison with multislice helical computed tomography. AB - PURPOSE: To determine the applicability of cone-beam computed tomography (CBCT) in otological imaging, and to compare its accuracy with the routinely used multislice helical CT (MSCT) for imaging of the middle- and inner-ear areas. MATERIAL AND METHODS: Thirteen unoperated human cadaver temporal bones were imaged with CBCT and MSCT. Sixteen landmarks of the middle and adjacent inner ear were evaluated and compared for their conspicuity according to a modified Likert scale. Total scores and scores for subgroups including landmarks of specific clinical interest were also compared. RESULTS: No significant differences were found between the imaging techniques or subgroups when scores of individual structures were compared. While the middle ear itself was visible in all cases with CBCT, parts of the inner ear were "cut off" in four cases due to the limited field of view. For the same reason, the evaluation of the whole mastoid was not possible with CBCT. The cochlear and vestibular aqueducts were not visualized in either CT techniques. The contrast-to-noise ratio was more than 50% lower in CBCT than in MSCT, but still adequate for diagnostic task. CONCLUSION: CBCT proved to be at least as accurate as routinely used MSCT in revealing the clinically and surgically important middle-ear structures. The results show that high-quality imaging of the middle ear is possible with the current CBCT device. PMID- 17354144 TI - Diffusion tensor imaging in patients with acute onset of neuropsychiatric systemic lupus erythematosus: a prospective study of apparent diffusion coefficient, fractional anisotropy values, and eigenvalues in different regions of the brain. AB - PURPOSE: To investigate whether apparent diffusion coefficient (ADC), fractional anisotropy (FA), and eigenvalues in neuropsychiatric systemic lupus erythematosus (NPSLE) patients differ from those of healthy controls. MATERIAL AND METHODS: Eight NPSLE patients (aged 23-55 years, mean 42.9 years) and 20 healthy age matched controls (aged 22-59 years, mean 44.4 years) underwent conventional brain magnetic resonance (MR) and diffusion tensor imaging (DTI). The ADC, FA, principal eigenvalue (lambda parallel), and the corresponding average perpendicular eigenvalue (lambda perpendicular) (=(lambda2+lambda3)/2) were measured in selected regions of normal appearing gray and white matter brain parenchyma. For statistical evaluation of differences between the two groups, a Student's t-test was used. The P value for statistical significance was set to P=0.0025 after Bonferroni correction for multiple measurements. RESULTS: Significantly increased ADC values were demonstrated in normal-appearing areas in the insular cortex (P<0.001), thalamus (P<0.001), and the parietal and frontal white matter (P<0.001 and P<0.001, respectively) in NPSLE patients. Significantly decreased FA values were demonstrated in normal-appearing thalamus (P<0.001), corpus callosum (P=0.002), and in the parietal and frontal white matter (P<0.001 and P<0.001, respectively) in NPSLE patients compared to healthy controls. The lambda perpendicular was significantly higher in several of these regions in NPSLE patients compared to healthy controls. CONCLUSION: Our study demonstrates alterations in normal-appearing gray and white matter brain parenchyma of patients with NPSLE by means of abnormal ADC, FA, and eigenvalues. These alterations may be based on loss of tissue integrity in part due to demyelination. It is possible that DTI in the future could assist in the diagnosis of NPSLE and possibly help to further elucidate the pathogenesis of NPSLE. PMID- 17354145 TI - Investigation of the effect of exhaust particles on ocular blood flow in highway toll collectors using color Doppler ultrasonography. AB - PURPOSE: To investigate the effect of exhaust particles on orbital blood flow velocity of the ophthalmic artery, central retinal artery, and posterior ciliary artery by color Doppler ultrasonography in highway toll collectors. MATERIAL AND METHODS: Color Doppler imaging was used to measure the peak-systolic and end diastolic flow velocities and resistivity indices of the ophthalmic artery, central retinal artery, and posterior ciliary artery in 20 toll collectors and 20 controls. RESULTS: Both the peak-systolic and the end-diastolic flow velocities were decreased in the ophthalmic artery, central retinal artery, and posterior ciliary artery, and the resistivity index was increased in the central retinal artery in toll collectors when compared with control groups. Results were considered statistically significant if P<0.05. CONCLUSION: It was determined that the effect of exhaust particles reduced ocular blood flow velocity in toll collectors as measured by color duplex Doppler ultrasonography. PMID- 17354146 TI - Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine. AB - PURPOSE: To evaluate the brains of newborns exposed to buprenorphine prenatally. MATERIAL AND METHODS: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5 T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. RESULTS: Neither structural abnormalities nor abnormalities in signal intensity were recorded. CONCLUSION: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process. PMID- 17354147 TI - Transrectal ultrasound performed immediately after prostate biopsy: imaging features and ultrasound-guided compression to bleeding biopsy tract. AB - PURPOSE: To evaluate the imaging features of transrectal ultrasound (TRUS) performed immediately after prostate biopsy, and to determine whether TRUS-guided compression can stop active bleeding. MATERIAL AND METHODS: Systematic 12-core biopsy was performed in 57 consecutive patients, 24 of whom underwent additional target biopsy. The imaging features of grayscale and power Doppler TRUS performed immediately after biopsy were prospectively analyzed, and the complication rate following TRUS-guided bleeding compression was registered. RESULTS: Hyperechoic, hypoechoic biopsy needle tracts, or both were seen in 88% (50/57), 72% (41/57), or 61% (35/57), respectively. Power Doppler TRUS performed immediately after biopsy showed 76 bleeding needle tracts in 43 of the 57 (75%) patients, of which 17 were on the right part of the gland and 59 were on the left (P<0.01). TRUS guided compression times ranged from 1 to 8 min (mean 2.9 min). Hematuria was seen in 38 of 57 patients (67%), with a mean duration of 2.6 days. Hematochezia was seen in 19 of 57 patients (33%), with a mean duration of 0.6 days. Hematuria lasting longer than 3 days occurred in 16 of 57 patients (28%). Hematospermia occurred in 13 of 40 cases (33%). CONCLUSION: TRUS performed immediately after biopsy depicted various imaging features and may control postbiopsy bleeding. PMID- 17354148 TI - Multiple skeletal muscle metastases from renal cell carcinoma 19 years after radical nephrectomy. AB - Skeletal muscle metastasis is a rare condition in renal cell carcinoma (RCC). We here present an extremely rare case of late recurrence in a patient with RCC who had multiple muscle metastases 19 years after radical nephrectomy. This case shows that a soft-tissue mass in a patient with a known history of RCC even after curative nephrectomy, particularly with hypervascularity, must be regarded as highly suspicious of skeletal muscle metastasis. PMID- 17354149 TI - Renal replacement lipomatosis: multidetector-row computed tomography findings in one case. AB - Replacement lipomatosis of the kidney is the result of severe atrophy of the renal parenchyma often caused by chronic calculus disease with secondary marked benign proliferation of fibrofatty tissue replacing atrophied renal parenchyma. Different radiological modalities have been used to illustrate this entity, with magnetic resonance imaging, ultrasound, intravenous pyelogram, and computed tomography (CT) used most frequently. We report multidedector CT (MDCT) findings of replacement lipomatosis in a 50-year-old woman. We think that it accurately provides a complete one-step diagnostic workup and appropriate pre-surgical planning for patients for whom there is a suspicion of replacement lipomatosis. PMID- 17354150 TI - Exceptional localization of extramedullary hematopoiesis: presacral and periureteral masses. AB - We report an exceptional case of periureteral and presacral localizations of extramedullary hematopoiesis. To our knowledge, the association of presacral or periureteral masses has not been described before. Diagnosis was suggested by the association of computed tomography (CT) imaging findings and knowledge of the clinical context. Guided CT biopsy is a safe and efficient means to obtain final diagnosis of atypical extramedullary hematopoiesis localizations. PMID- 17354152 TI - Can selective serotonin inhibitor drugs in elderly patients in nursing homes be reduced? AB - OBJECTIVE: To investigate whether treatment with selective serotonin reuptake inhibitors (SSRIs) could be withdrawn for elderly residents who had been on treatment for at least one year and to evaluate a method for systematic drug review. DESIGN: Open, prospective, interventional study. SETTING: Four counties in Sweden. SUBJECTS: Elderly residents at 19 nursing homes, with ongoing treatment with SSRIs for more than one year. MAIN OUTCOME MEASURES: Clinical evaluation, registration of drugs used and rating with Montgomery-Asberg Depression Rating Scale (MADRS). A semi-structured telephone interview with 15 participating physicians and 19 nurses. RESULTS: About one-third of all 822 residents in the nursing homes had ongoing antidepressant treatment, predominantly with SSRIs; 75% of them had been treated with SSRIs for at least one year and 119 (60%) of these were considered eligible for the study. The intervention was judged successful in 52% of these residents of whom 88% had a MADRS rating of less than 20 points. The GPs and the nurses experienced the method as practicable. CONCLUSIONS: Withdrawal of SSRI treatment was successful in the majority of cases. The MADRS may be a valuable addition to clinical evaluation when deciding whether to end or continue SSRI treatment. PMID- 17354153 TI - Evaluation of the quality of drug therapy among elderly patients in nursing homes. AB - OBJECTIVE: To evaluate drug therapy quality among elderly nursing home residents. Secondary aims were to compare quality in young and old elderly and to determine whether number of prescribers affected quality of drug therapy. DESIGN: A cross sectional population-based register study. SETTING: Nursing home residents in the Gothenburg area using the multi-dose system (e.g. patients who get their drugs machine dispensed into one unit for each dose occasion, a service offered by the National Corporation of Pharmacies). SUBJECTS: All nursing home residents aged 65 years and older. MAIN OUTCOME MEASURES: The quality of drug therapy assessed using five quality indicators for the elderly recently introduced by the Swedish National Board of Health and Welfare; number of prescribed drugs per resident. RESULTS: Over 70% of residents had one or more potentially inappropriate prescription. Younger nursing home residents (65-79 years) had significantly (p < 0.001) lower quality of drug therapy than older residents (80 + ). The average number of prescribing physicians per resident was high at almost four per resident. An increasing number of prescribers per resident was associated with a higher number of drugs prescribed and a lower quality of drug therapy. CONCLUSION: Computerized quality assurance systems can provide support for healthcare providers. Quality indicators should be modified to give maximum support for users. PMID- 17354154 TI - General practitioners' views on radiology reports of plain radiography for back pain. AB - OBJECTIVE: To identify and describe general practitioners' (GPs') views on radiology reports, using plain radiography for back pain as the case. DESIGN: Qualitative study with three focus-group interviews analysed using Giorgi's method as modified by Malterud. SETTING: Southern Norway. SUBJECTS: Five female and eight male GPs aged 32-57 years who had practised for 3-15 years and were from 11 different practices. MAIN OUTCOME MEASURES: Descriptions of GPs' views. RESULTS: GPs wanted radiology reports to indicate more clearly the meaning of radiological terminology, the likelihood of disease, the clinical relevance of the findings, and/or the need for further investigations. GPs stated that good referral information leads to better reports. CONCLUSION: These results can help to improve communication between radiologists and GPs. The issues identified in this study could be further investigated in studies that can quantify GPs' satisfaction with radiology reports in relation to characteristics of the GP, the radiologist, and the referral information. PMID- 17354155 TI - General practitioners' relationship to sickness certification. AB - OBJECTIVE: GPs' role conflict in connection with sickness certification is widely accepted. The authors explored the relationship between GPs and this difficult task. DESIGN: Cross-sectional questionnaire study of experiences, attitudes, and management of sickness certification. Data were analysed by hierarchical cluster analysis. SETTING: Norway. SUBJECTS: Representative sample of 308 general practitioners from a nationwide panel established by the Research Institute of the Norwegian Medical Association. MAIN OUTCOME MEASURES: Differentiation of response patterns regarding perceived burden, self-evaluation, doubt, permissiveness, opinions on whether sickness certification is a medical task, and sociopolitical attitude. Associations with hours of patient contact per week, number of sickness certifications per week, job satisfaction, degree of paternalism, and personality characteristics. RESULTS: Four groups evolved, one (12%) with low burden, high self-esteem, little doubt, and permissiveness, another (12%) with the opposite characteristics. They displayed similar sociopolitical attitudes. The third group (32%) was primarily characterized by a biomedical attitude, while the fourth represented a middle position in all dimensions. The first two groups differed on personality characteristics. There were no differences between groups regarding number of sickness certifications per week, job satisfaction, or degree of paternalism. CONCLUSIONS: Prominent differences in experiences with sickness certification between groups of doctors exist. No evidence was found of associations between group-level GP differences and sickness certification rates. PMID- 17354156 TI - Access to and continuity of primary medical care of different providers as perceived by the Finnish population. AB - OBJECTIVE: To study people's views on the accessibility and continuity of primary medical care provided by different providers: a public primary healthcare centre (PPHC), occupational healthcare (OHC), and a private practice (PP). DESIGN: A nationwide population-based questionnaire study. SETTING: Finland. SUBJECTS: A total of 6437 (from a sample of 10,000) Finns aged 15-74 years. MAIN OUTCOME MEASURES: Period of time (in days) to get an appointment with any physician was assessed via a single structured question. Accessibility and continuity were evaluated with a five-category Likert scale. Values 4-5 were regarded as good. RESULTS: Altogether 72% had found that they could obtain an appointment with a physician within three days, while 6% had to wait more than two weeks. Older subjects and subjects with chronic diseases perceived waiting times as longer more often than younger subjects and those without chronic diseases. The proportion of subjects who perceived access to care to be good was 35% in a PPHC, 68% in OHC, and 78% in a PP. The proportion of subjects who were able to get successive appointments with the same doctor was 45% in a PPHC, 68% in OHC, and 81% in a PP. A personal doctor system was related to good continuity and access in a PPHC. CONCLUSIONS: Access to and continuity of care in Finland are suboptimal for people suffering from chronic diseases. The core features of good primary healthcare are still not available within the medical care provided by public health centres. PMID- 17354157 TI - Patients' written life stories: a gateway for understanding. AB - OBJECTIVE: To explore how statements drawn from patients' written life stories can help general practitioners understand their patients' maladaptive thought patterns and their negative schemata. DESIGN: Qualitative study of written life stories. SETTING: General practice in Copenhagen, Denmark. SUBJECTS: A total of 22 consecutive patients aged 23-49 years, who were invited by their GP to participate in cognitive therapy owing to depressive or anxiety-related disorders, including unexplained bodily symptoms. THEORETICAL FRAME OF REFERENCE: Beck's information-processing model of anxiety. RESULTS: Analysis of the written life stories disclosed aspects of negative expectations of life, the self, or the values and capabilities of others or of the patient him- or herself. Three main beliefs were identified: (1) the world is evil, (2) only the perfect is of value, and (3) emotions are dangerous. The patients describe events and experiences in negative terms that others might have interpreted as neutral or positive. For some this translated into a sort of all-or-nothing kind of thinking. Anger and other strong feelings were forbidden. Responsibility for the life of others was a dominant feature. CONCLUSIONS: Written life stories reveal knowledge of the patient's dysfunctional thought patterns. This may be a useful shortcut in therapy. PMID- 17354158 TI - Concepts of risk among young Swedes tested negative for HIV in primary care. AB - OBJECTIVE: To explore why young adults test for HIV, how they construct the HIV risk, and what implications testing has for them. DESIGN: Six tape-recorded focus group interviews were transcribed verbatim and analysed according to a grounded theory approach. SUBJECTS AND SETTING: Women and men between 18 and 24 years of age were recruited from a youth clinic in northern Sweden in 2004-05 after being tested and found to be HIV negative. RESULTS: A core category--reconsidering risk and four categories--HIV: a distant threat; the risk zone; responsibility: a gendered issue; a green card-- emerged. HIV was described as being far away. Stereotypical images of risk actors emerged but were perceived to be cliches. "Ordinary" people including themselves were also considered at risk. Many had event-driven reasons for testing for HIV, multiple partners being one. One closer risk zone was "the bar"; a dating milieu that often was expected to include "one night stands" for both women and men. Responsibility for testing was a gendered issue: it was "natural" for women, while men rather "escaped from responsibility". A resistance towards testing was revealed among young men. Receiving a negative HIV test result was "a green card", confirming healthiness and providing relief. Most informants felt "clean" and discussed how to restart with renewed ambitions. CONCLUSIONS: As participating in focus-group interviews was apparently an "eye-opener" for many, a counselling conversation reconsidering risk following an HIV test might be a good idea. Liberal HIV testing among young men and women could evoke insights and maturation and start a process of reflections concerning their sexual risk-taking behaviour. PMID- 17354159 TI - Women's strategies for handling chronic muscle pain: a qualitative study. AB - OBJECTIVE: Medicine lacks good models for understanding and treating chronic muscle pain. The aim of this study was to explore whether participation in a treatment group for women with chronic muscle pain can help the participants to develop strategies to handle their chronic muscle pain. METHODS: The study was carried out as a qualitative research project. Eight women completed a treatment programme consisting of movement training and group discussions. The qualitative data consisted of transcriptions from audio-taped individual interviews. The data material was analysed by systematic text condensation inspired by Giorgi. RESULTS: All the women describe participation in the treatment group as useful. Their experiences could be categorized as follows: To know oneself, to negotiate with oneself and others, to be able to choose, and to be able to act. CONCLUSION: The participants developed strategies for handling their chronic muscle pain. Both the women's new understanding of their chronic muscle pain and increased confidence in themselves were important. These phenomena can help women in their encounters with their surroundings, for example when consulting doctors. The doctor's awareness of the women's resources and their own mastering strategies may contribute to a new understanding of the disposing, triggering, and maintaining factors, and of the curative and health-promoting forces at work in those with chronic muscle pain. PMID- 17354160 TI - Clinical and bacteriological outcome of different doses and duration of pivmecillinam compared with placebo therapy of uncomplicated lower urinary tract infection in women: the LUTIW project. AB - OBJECTIVE: To analyse associations between symptoms and bacteriuria in uncomplicated lower urinary tract infection in women (LUTIW) and to evaluate outcome of therapy with three different regimens of pivmecillinam or placebo. DESIGN: Prospective, multicentre, randomized, double-blind, and placebo controlled therapy study. Symptoms registered at inclusion, during therapy and at follow-up visits after 8-10 and 35-49 days. Significant bacteriuria defined according to current European guidelines. SETTING: A total of 18 primary healthcare centres in northern Sweden. Subjects. Women aged 18 years and above with symptoms of urgency, dysuria, supra pubic or loin pain. Main outcome measures. Symptoms and bacteriuria at inclusion and course of symptoms, bacteriuria, and their combinations during and post-therapy. RESULTS: At inclusion, no associations or significant differences were found between symptom scores and bacteriuria, bacterial counts, or species. The 884 patients (77%) with significant bacteriuria were followed up. All pivmecillinam therapies were superior to placebo (p < 0.001). From day six until first follow-up, the mean values of all symptoms were higher and the bacteriological cure was lower at first follow-up in the three days (84%) compared with the seven days regimens (93 94%, p < 0.001). At final follow-up clinical cure was similar in all pivmecillinam regimens (65-72%) as was bacteriological cure (83-89%). Pivmecillinam had few low to mild adverse reactions, comparable to placebo. CONCLUSIONS: Symptoms are not conclusive for diagnosis of LUTIW. Pivmecillinam therapies are superior to placebo and seven days regimens are more efficient than three days. Pivmecillinam 200 mg x 2 x 7 days is recommended as a first-line therapy for LUTIW. PMID- 17354161 TI - Being lesbian--does the doctor need to know? AB - BACKGROUND: A lesbian woman will have to choose whether to disclose or not in every new encounter, including when consulting her general practitioner (GP). She may fear a negative reaction in the doctor, based on knowledge of marginalization and prejudice of homosexuals throughout history. OBJECTIVES: To explore patients' experiences concerning disclosure of their lesbian orientation to general practitioners (GPs), focusing on why they find it important, and what GPs can do to promote disclosure. METHODS: One group interview was conducted, audiotaped, and transcribed verbatim. Qualitative analysis was conducted by systematic text condensation inspired by Giorgi's phenomenological approach. Six women aged 28-59 years, who self-identified as lesbian, were recruited through a web-based, publicly accessible network for research on homosexuality. Main outcome measures. Accounts of experiences where the patient thought that information of a lesbian sexual orientation was of importance in the consultation with a GP. RESULTS: Disclosure can imply information of medical relevance, explain circumstances, and generate a feeling of being seen as one's true self. The intentional use of common consultation techniques may facilitate disclosure. CONCLUSION: Lesbian patients may want to disclose their sexual orientation to the general practitioner but they experience certain barriers. These can be overcome when the GP provides an open and permissive context. GPs can benefit from knowledge concerning sexual orientation in their work with lesbian patients. PMID- 17354163 TI - Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin- from bench to bedside. AB - Secondary metabolites from plants serve as defense against herbivores, microbes, viruses, or competing plants. Many medicinal plants have pharmacological activities and may, thus, be a source for novel treatment strategies. During the past 10 years, we have systematically analyzed medicinal plants used in traditional Chinese medicine and focused our interest on Artemisia annua L. (qinhao, sweet wormwood). We found that the active principle of Artemisia annua L., artemisinin, exerts not only antimalarial activity but also profound cytotoxicity against tumor cells. The inhibitory activity of artemisinin and its derivatives towards cancer cells is in the nano- to micromolar range. Candidate genes that may contribute to the sensitivity and resistance of tumor cells to artemisinins were identified by pharmacogenomic and molecular pharmacological approaches. Target validation was performed using cell lines transfected with candidate genes or corresponding knockout cells. The identified genes are from classes with diverse biological functions; for example, regulation of proliferation (BUB3, cyclins, CDC25A), angiogenesis (vascular endothelial growth factor and its receptor, matrix metalloproteinase-9, angiostatin, thrombospondin 1) or apoptosis (BCL-2, BAX, NF-kappaB). Artesunate triggers apoptosis both by p53-dependent and -independent pathways. Antioxidant stress genes (thioredoxin, catalase, gamma-glutamylcysteine synthetase, glutathione S-transferases) as well as the epidermal growth factor receptor confer resistance to artesunate. Cell lines overexpressing genes that confer resistance to established antitumor drugs (MDR1, MRP1, BCRP, dihydrofolate reductase, ribonucleotide reductase) were not cross-resistant to artesunate, indicating that artesunate is not involved in multidrug resistance. The anticancer activity of artesunate has also been shown in human xenograft tumors in mice. First encouraging experience in the clinical treatment of patients suffering from uveal melanoma calls for comprehensive clinical trials with artesunate for cancer treatment in the near future. PMID- 17354164 TI - Evaluation of the anti-inflammatory activity of luteolin in experimental animal models. AB - Luteolin, a flavonoid abundant in plants worldwide, demonstrates a spectrum of biological activities. This study is aimed at evaluating its inhibiting effects on inflammatory responses in vivo. We investigated the anti-inflammatory activity of luteolin in acute and chronic models in mice. We found that oral administration of luteolin (10 and 50 mg/kg) efficiently suppressed paw edema when induced by injecting carrageenan, and a similar tendency was also observed in the cotton pellet granuloma test. In the air pouch test, luteolin markedly reduced the number of infiltrated leukocytes and the elevated level of 6-keto prostaglandin F1alpha (6-keto-PGF1alpha) in the exudate. The results derived from the whole blood assay for cyclooxygenase (COX) and from the reverse transcription polymerase chain reaction (RT-PCR) assay indicate that luteolin may be a potent selective inhibitor of cyclooxygenase-2 (COX-2) and that the inhibition is attributable to its down-regulation of the mRNA expression of COX-2 in inflammatory responses. PMID- 17354165 TI - Therapeutic effect of combined triptolide and glycyrrhizin treatment on rats with collagen induced arthritis. AB - For investigating the effects of a combination therapy of triptolide (TP) with glycyrrhizin (GL) in rats with collagen-induced arthritis (CIA), the arthritic index was examined, and the levels of anti-CII IgG, TNF-alpha and IL-10 in serum were measured by ELISA. Our results showed that combined triptolide and glycyrrhizin treatment (TP 13.40 microg, GL 26.78 mg) can reduce the arthritic index of CIA rats and decrease the level of anti-CII IgG and TNF-alpha in serum. The observed effect was similar to the one measured upon application of TP 17.86 microg, GL 26.78 mg and TP 17.86 microg. The level of IL-10 was not significantly different among the rats of the TP 17.86 microg, of the TP 17.86 microg, GL 26.78 mg and of the TP 13.40 microg, GL 26.78 mg groups while the IL-10 levels in rats of the TP 13.40 microg and GL 26.78 mg groups were significantly higher. Combined triptolide 13.40 microg and glycyrrhizin 26.78 mg can therefore significantly inhibit collagen induced arthritis, and the effect was similar to the one of triptolide at 17.86 microg. PMID- 17354166 TI - Effects of differential extraction of Verbena officinalis on rat models of inflammation, cicatrization and gastric damage. AB - Verbena officinalis L. is used in folk medicine for the treatment of inflammatory disorders, skin burns, abrasions, and gastric diseases. Extracts obtained with different solvents (methanol, VoME; enriched flavonoids, VoEF; supercritical CO2, VoCO2) were evaluated for anti-inflammatory, gastroprotective and cicatrizing activities. Additionally, the antioxidant capacity was determined in vitro. In order to confirm the activities investigated, histological observations were performed. All extracts induce a remarkable anti-inflammatory activity. The gastric damage is significantly reduced by all extracts administered, whereby the most pronounced protection is observed for the VoCO2 and VoEF extracts. Finally, a wound healing effect is obtained particularly by the CO2 extract, suggesting the presence of some lipophilic active principles. Histological evidence confirms the results evaluated with the animal procedures. The results obtained after oral administration of V. officinalis extracts are also in agreement with the antioxidant capacity evaluated in vitro, confirming the relationship between pharmacological activities and antiradical efficacy. PMID- 17354167 TI - Coadministration of the aromatase inhibitor formestane and an isopropanolic extract of black cohosh in a rat model of chemically induced mammary carcinoma. AB - Non-steroidal as well as steroidal aromatase inhibitors are currently being discussed as alternatives to tamoxifen in the first-line treatment of patients with hormone-dependent breast cancer. Many of these women are in a postmenopausal state and additionally troubled by climacteric complaints. Naturally occurring symptoms like hot flushes and night sweats can be triggered or augmented by anti hormonal drugs. At the aromatase molecule, steroidal inhibitors like exemestane and formestane compete with the hormonal precursors for the substrate binding site and inactivate the enzyme irreversibly. An isopropanolic extract of the rootstock of black cohosh (iCR), which is a common comedication of aromatase inhibitors in breast cancer patients suffering from climacteric symptoms, contains triterpene glycosides and cinnamic acid esters, both of which possess structural similarities to steroids. We therefore tested a high dose of iCR, guaranteeing an effective uptake of 60 mg herbal substance per kg body weight and shown to influence rat bone and uterus, for putative interactions with two low dosing regimens of 3.5 mg or 5.0 mg formestane per animal and day. We chose a rat model of chemically induced breast cancer and evaluated tumor growth and serum estrogen levels. Compared to a tumor area of 1400 mm2 after 21 days of unopposed tumor growth, formestane treatment, irrespective of concomitant black cohosh application, significantly reduced neoplastic growth by 50%. Formestane also significantly reduced serum estrogen levels, an effect which was also not abolished by iCR. Therefore, in this experimental setting, when challenging two low doses of formestane with a high dose of iCR, our data do not raise concerns against combining aromatase inhibitors with black cohosh. PMID- 17354168 TI - Two new depsipeptides from the marine fungus Spicellum roseum. AB - Investigation of the secondary metabolites of the marine-derived fungus Spicellum roseum yielded two new cyclohexadepsipeptides, spicellamide A (1) and spicellamide B (2). The structures of 1 and 2 were determined based on extensive evaluations of NMR and MS data. The absolute configuration was deduced after hydrolysis using Marfey's method, chiral chromatography, as well as NOESY and modeling data. PMID- 17354169 TI - Leishmanicidal constituents from the leaves of Piper rusbyi. AB - The kavapyrone (+)-(7 R,8 S)-epoxy-5,6-didehydrokavain (1) and the chalcone flavokavain B (2) were isolated from Piper rusbyi as the bioactive components by bioassay-guided fractionation, using an in vitro assay against promastigote forms of three Leishmania strains. In addition, the new kavapyrone, (7 R,8 R/7 S,8 S) dihydroxy-5,6-didehydrokavain (3), which is very likely an artifact, and four known compounds (4-7) were isolated. Their structures were elucidated on the basis of spectral analysis, and the absolute configurations of compounds 1 and 3 were established by CD studies and the modified Mosher ester procedure, respectively. All compounds were evaluated for in vitro leishmanicidal activity. The most active compounds 1 (IC50=81.9 microM) and 2 (IC50=11.2 microM) were also evaluated in vivo against a New World strain of cutaneous leishmaniasis, and the results showed the efficacy of 2 at a dose of 5 mg/kg/day. Compounds 1 and 3 were also assayed as reversal agents against a multidrug-resistant Leishmania tropica line, but were found to be inactive. PMID- 17354170 TI - Two major urinary metabolites of scutellarin in rats. AB - Urinary metabolites of scutellarin, the main effective constituent of breviscapine, a cerebrovascular and cardiovascular drug consisting of total flavonoids of Erigeron breviscapus, were investigated in rats. Two major metabolites were isolated from the urine of rats following oral administration of scutellarin and identified as scutellarein 6,7-di- O-beta-D-glucuronide (M1) and scutellarein (M2), respectively, on the basis of chemical and spectroscopic evidence. M1 was reported as a metabolite of scutellarin for the first time. PMID- 17354171 TI - Evaluation of antifungal and DNA-damaging activities of alkaloids from branches of Porcelia macrocarpa. AB - Bioactivity-guided fractionation of the alkaloidal fractions of the CH2Cl2 extract from branches of Porcelia macrocarpa using mutant yeast strains of Saccharomyces cerevisiae and fungi Cladosporium cladosporioides and C. sphaerospermum led to the isolation of bioactive alkaloids: two tetrahydrobenzylisoquinolines (1 and 2), two aporphines (3 and 4), one proaporphine (5), one oxoaporphine (6), four azantraquinones (7-10) and four azafluorenones (11-14). The alkaloids cleistopholine (7) and 6 methoxycleistopholine (8) showed the highest fungitoxic activity while the mixture of 6- and 7-methoxyonychine (12+13) and 6,7-dimethoxyonychine (14) showed a weak DNA-damaging potential. PMID- 17354172 TI - Alkaloids from Melochia chamaedrys. AB - Investigation of the chemical constituents from the roots of Melochia chamaedrys (Sterculiaceae) resulted in the isolation of two quinolinone alkaloids: a new alkaloid, named chamaedrone (1), and a known alkaloid, antidesmone (2). Their structures and stereochemistry were elucidated on the basis of 2D NMR and X-ray crystallographic analysis. Furthermore, alkaloids 1 and 2, and the synthetic analogues 3-6 obtained from 2, were screened for antimicrobial activities. PMID- 17354173 TI - Synthesis and spectroscopic characterization of cannabinolic acid. AB - Cannabinoids, the main constituents of the cannabis plant, are being increasingly studied for their medicinal properties. Cannabinolic acid (CBNA; 1) was synthesized from tetrahydrocannabinolic acid (THCA; 2), a major constituent of the cannabis plant, by aromatization using selenium dioxide mixed with trimethylsilyl polyphosphate as catalyst in chloroform. Purification was achieved by centrifugal partition chromatography, and the final product had a purity of over 96% by GC analysis. Spectroscopic data on CBNA such as 1H-NMR and IR, and molar extinction coefficients, as well as chromatographic data are presented as useful references for further research on CBNA. The developed method allows production of CBNA on a preparative scale, making it available for further studies on its biological activities as well as use as a reference standard for analytical procedures. PMID- 17354174 TI - Biliorenous fistula related to self-expandable biliary metallic stent placement: a rare complication of endoscopic retrograde cholangiopancreatography. PMID- 17354175 TI - Unexplained diarrhea in a patient with a percutaneous endoscopic gastrostomy (PEG) tube. PMID- 17354176 TI - Endoscopic ultrasound-guided pancreaticogastrostomy reconstruction. PMID- 17354177 TI - Video capsule endoscopy in the diagnosis of gastrointestinal Kaposi's sarcoma. PMID- 17354178 TI - Endoscopic removal of giant Brunneroma presenting as a large pedunculated polyp. PMID- 17354179 TI - Pneumatosis cystoides coli of the ascending colon: colonoscopic and CT colonographic features. PMID- 17354180 TI - Fatal complication of gastric tear at diagnostic colonoscopy with deep sedation. PMID- 17354181 TI - Endoscopic submucosal dissection for rectal tumors. AB - BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) has recently been developed for one-piece resection of gastric tumors. In order to improve patients' quality of life, it may be desirable to use the same technique for rectal tumors. METHODS: 35 consecutive patients with rectal tumors were enrolled. ESD was carried out using the same technique as for the stomach. The efficacy, technical feasibility, operation time, complications, and follow-up results were assessed. RESULTS: The mean size of the epithelial tumors was 26.2 +/- 14.0 mm, and the rates of one-piece resection and one-piece resection with tumor-free margins were 73.3% (22 of 30) and 70.0% (21 of 30), respectively. The median operation time was 70 min (range 8-360 min). All five carcinoid tumors were completely resected. No patient needed blood transfusion or had the complication of problematic bleeding. Perforation during ESD occurred in one patient (2.9%), who was managed with conservative medical treatment after endoscopic closure of the perforation. Excluding seven patients, who either underwent additional surgery or whose follow-up period was less than 1 year, all 23 patients with epithelial tumors were free of recurrence during a mean follow-up period of 25.7 months (range 12-53 months). CONCLUSIONS: ESD was thus found to be feasible for the treatment of rectal tumors, with promising results although the follow-up periods were short. ESD may therefore be indicated for rectal tumors which are not resectable en bloc by conventional procedures, in order to improve the patients' quality of life. PMID- 17354182 TI - Improvement of tissue-adhesive obliteration of bleeding gastric varices using adjuvant hypertonic glucose injection: a prospective randomized trial. AB - BACKGROUND AND STUDY AIMS: Rebleeding can occur after endoscopic injection of gastric varices with tissue adhesive. The aim of this study was to evaluate whether adjuvant hypertonic glucose solution injections enhance the effects of Histoacryl after successful initial variceal obliteration. PATIENTS AND METHODS: A total of 67 patients (37 men, 30 women; mean age +/- standard deviation [SD] 60 +/- 17 years) with initially successful Histoacryl obliteration of bleeding gastric varices were included in the study and randomly divided into two groups: a "combined" group of patients who had adjuvant injection of hypertonic glucose solutions in cases of residual gastric varices (F1 or less) and a "control" group of patients who did not receive such therapy. End points were either variceal recurrence/progression (F2 or more) requiring Histoacryl reinjection or rebleeding. RESULTS: Residual small varices were found in 56% of patients in the combined group and in 60% of patients in the control group. Adjuvant therapy was only performed in the combined group. During the follow-up period (mean duration +/- SD 37.9 +/- 18.5 months, range 19-56 months), two patients in the combined group showed gastric variceal progression, compared with nine patients showing progression in the control group, with two cases of rebleeding, both occurring in the control group. Two years after the first Histoacryl injection, the cumulative proportion of patients who did not have gastric variceal progression was significantly higher in the combined group than it was in the control group (92.8% vs. 71.4%, P = 0.029). There was no significant difference between the two groups with respect to their survival curves (P = 0.12). No marked immediate or delayed symptoms or complications were observed in the patients given hypertonic glucose injections. CONCLUSIONS: Adjuvant treatment with hypertonic glucose solution for residual small gastric varices is a safe and simple method. It helps reduce the recurrence or progression of gastric varices after tissue adhesive injections and can therefore reduce the risk of rebleeding. PMID- 17354183 TI - The value of endoscopic rectal ultrasound in predicting the lateral clearance and outcome in patients with lower-third rectal adenocarcinoma. AB - BACKGROUND AND STUDY AIMS: The aim of this study was to assess whether preoperative endorectal ultrasound (ERUS) is able to predict histological infiltration of the external anal sphincter or the levator ani muscle in patients with a lower-third rectal neoplasm and so the possibility of treatment by sphincter-saving surgery. PATIENTS AND METHODS: Between May 1996 and May 2003, 66 patients with a lower-third rectal neoplasm that was staged as uT2 or greater were entered into a prospective evaluation of ERUS. All patients underwent neoadjuvant treatment before surgery. RESULTS: The first ERUS (ERUS 1) was performed before neoadjuvant treatment; the second ERUS (ERUS 2) was performed between the end of the radiotherapy and the surgery. An abdominoperineal resection was performed mainly when the lower extent of the tumor was within 3.5 cm from the anal verge (P = 0.011), but no correlation was observed between the lateral clearance determined by ERUS 1 and the histological clearance (P = 0.091). After neoadjuvant treatment, the ERUS 2 lateral clearance was significantly correlated with the type of surgery (P = 0.003) and the histological clearance (P < 0.001). With regard to the performance of ERUS 2 for predicting histological infiltration of the external anal sphincter or the levator ani muscle, the sensitivity was 100%, the negative predictive value was 100%, the specificity was 87%, and the positive predictive value was 53%. In a multivariate analysis, the histological clearance and tumor T stage were statistically correlated with disease-free survival (P = 0.035 and P = 0.05, respectively). CONCLUSIONS: ERUS could help oncologists and surgeons in the management of patients with lower rectal carcinomas. Moreover, ERUS is able to predict lateral histological clearance after neoadjuvant treatment. PMID- 17354184 TI - [Depressogenic effects of beta-receptor blockers--a medical myth?]. PMID- 17354185 TI - [Forensic psychiatry]. PMID- 17354186 TI - Evaluation of cerebral glioma grade by using normal side creatine as an internal reference in multi-voxel 1H-MR spectroscopy. AB - PURPOSE Our purpose was to evaluate cerebral glioma grade by using normal side creatine (Cr) as an internal reference in multi-voxel 1H-MR spectroscopy. MATERIALS AND METHODS We examined 25 adult patients with glial brain tumors. Ratios of maximum Cho/Cr (normal) (max- Cho/Cr(n)) and minimum NAA/Cr(normal) (min-NAA/ Cr(n)) were determined using Cr levels in the normal parenchyma. In addition, maximum Cho/Cr (max- Cho/Cr) and minimum NAA/Cr (min-NAA/Cr) were calculated from spectrum in the tumor areas. Tumors were graded according to metabolite ratios and the findings were compared to histopathological test results. The sensitivity, specificity, positive and negative predictive values of metabolite ratios were determined. RESULTS The ratio of max-Cho/Cr(n) was lower than that of max-Cho/Cr in the high-grade group (P = 0.001). Min-NAA/Cr(n), min NAA/Cr, and max-Cho/Cr ratios demonstrated statistically significant differences between high-grade (n = 19) and low-grade tumors (n = 6). The min-NAA/Cr and min NAA/Cr(n) ratios were inversely correlated with tumor grade (P = 0.027 and P = 0.009, respectively). CONCLUSION Use of normal side Cr as an internal reference provides a more objective evaluation for brain tumor grading. Our data showed that Cr tended to be low in the high-grade tumors. In addition to conventional metabolite ratios, the Min-NAA/Cr(n) ratio might be useful in brain tumor grading. Combined use of metabolite ratios might be helpful in grading brain tumors in cases without significantly increased Cho/Cr ratios. PMID- 17354187 TI - Incidental bilateral accessory middle cerebral arteries on MR imaging and MR angiography. AB - Intracranial vascular variations involving the middle cerebral artery are rarely seen. Herein, we report an 11-year-old girl with incidental bilateral accessory middle cerebral arteries, an extremely rare variation, which is the first case in the related literature demonstrated by cranial magnetic resonance imaging and magnetic resonance angiography. PMID- 17354188 TI - The role of US and MR imaging in detecting local chest wall tumor recurrence after mastectomy. AB - PURPOSE: To determine the role of clinical examination, ultrasonography (US), and magnetic resonance imaging (MRI) in detecting local tumor recurrence in patients who underwent modified radical mastectomy for breast cancer. MATERIALS AND METHODS: The study included 27 patients who were examined between April 1999 and April 2003. US evaluation of the chest wall was performed in all patients. MRI was performed on 10 patients due to suspicious findings in clinical examination, on 3 patients due to US findings, and on 8 patients due to both US and clinical examination findings. Six patients without any suspicious findings underwent MRI for follow-up purposes. The lesions detected with MRI were evaluated according to their morphology, contrast enhancement characteristics and dynamics. The focal lesions that enhanced intensely at the early phase were accepted as suspicious for malignancy. RESULTS: Of the 10 cases that underwent biopsy secondary to suspicious lesions for malignancy according to MRI findings, 7 were found to have recurrence. In the remaining 3 patients, recurrence diagnosis was made based on the fact that the lesions regressed in response to chemotherapy. In 17 cases, there were no suspicious findings on MRI for local recurrence. In 2 of these cases, biopsies were performed due to suspicious US findings; however, no malignancies were detected. The sensitivity and specificity of clinical examination in detecting local recurrence was 70% and 35.2%, respectively. These values were 90% and 88.2% for US, and 100% and 100% for MRI. CONCLUSION: In patients with mastectomy, US and MRI were more successful in detecting local recurrence than clinical examination. Considering the fact that US is cheaper and more readily available than MRI, it should be part of the routine follow-up in order to detect local recurrence early. MRI will be helpful in cases with suspicious US findings by increasing the specificity of the evaluation as well as determining the actual size and spread of any lesions, which is valuable information for the subsequent management and response to the particular treatment. PMID- 17354189 TI - Closed perforation of the small bowel secondary to a phytobezoar: imaging findings. AB - Small bowel perforation secondary to phytobezoars is a rare clinical entity, which is not well-documented in the radiological literature. Sonographic and computed tomography (CT) findings of a case of closed small bowel perforation secondary to phytobezoars in a patient with previous gastric surgery are presented. Both abdominal ultrasound and CT examinations revealed a collection containing air at the left lower quadrant as well as neighboring intraluminal masses suggestive of bezoars. We propose that appropriate CT examination is a very useful imaging modality for evaluating this kind of bowel perforation. PMID- 17354190 TI - Clinical and CT findings of epiploic appendagitis within an inguinal hernia. AB - Epiploic appendagitis is a rare condition resulting from an acute inflammation of an appendix epiploica. Epiploic appendagitis is frequently misdiagnosed as either acute appendicitis or acute diverticulitis, and the diagnosis is usually made during surgery. Epiploic appendagitis is a rare, self-limiting condition, which can be easily diagnosed with computed tomography (CT). Imaging with CT may suggest the diagnosis thus preventing unnecessary surgery. Medical management of symptoms is usually sufficient. Herein, we present CT findings of an epiploic appendagitis case that developed in a left inguinal hernia, which is a very rare entity. PMID- 17354191 TI - Echogenic foci mimicking adenomyosis presumably due to air intravasation into the myometrium during sonohysterography. AB - PURPOSE: To report the radiological findings of a pseudolesion in the myometrium mimicking adenomyosis presumably due to air intravasation during sonohysterography (SHG). MATERIALS AND METHODS: We searched magnetic resonance imaging (MRI) and transvaginal ultrasound (TVUS) examination results before and after SHGs, in which echogenic foci were found suggesting adenomyosis in the myometrium, and found 7 female cases. MRI and TVUS findings were compared to the SHG findings to assess the persistence of echogenic foci seen with SHG and other imaging modalities, and to exclude the possibility of pseudolesions secondary to saline-air intravasation into the myometrium during SHG. RESULTS: Ages of the 7 patients ranged from 27 to 60 years; 2 of them were postmenopausal. SHG examinations showed solitary or multiple echogenic foci measuring 4-15 mm, with acoustic shadowing, which were adjacent to the endometrium and consistent with adenomyosis. Only 1 of the patients underwent both MRI and TVUS, 2 of them had TVUS after SHG, and 1 had TVUS before SHG; the 3 remaining patients had TVUS as a baseline examination prior to SHG. None of these TVUS or MRI examinations confirmed the echogenic foci found with SHG. CONCLUSION: In order to differentiate echogenic myometrial pseudolesions from true adenomyosis lesions, a detailed preliminary TVUS is essential before any SHG procedure. If such lesions are encountered despite meticulous care to avoid the inadvertent introduction of air into the endometrial cavity, TVUS findings should be reviewed and a pelvic MRI is recommended in cases with heterogeneous myometrium. PMID- 17354192 TI - The low anterior cervical approach to the upper thoracic vertebrae: a decision by preoperative MR imaging. AB - PURPOSE: Surgical approaches to the upper thoracic spine are fraught with many problems as they involve thoracotomy or sternotomy. We analyzed 102 midsagittal MRI scans to evaluate the level of the sternal notch in relation to the upper thoracic spine, so that if the tangential line through the upper part of the sternal notch passed below the level of the involved vertebra, we could surgically access the involved vertebra by the low anterior cervical approach, which is familiar to most spinal surgeons. MATERIALS AND METHODS: Between January and June 2002, 102 consecutive mid-sagittal T2 weighted MRI scans were evaluated. The line as described above was then drawn on each MRI to assess the level of the involved vertebra. RESULTS: In 68.7% of the cases, the level of the sternal notch corresponded to T2 and T3. This method of assessing accessibility was used in a patient with a fractured T3 that yielded excellent surgical exposure. It was found that routine use of saturation bands is not needed in upper thoracic spine pathology as it obscured the visualization of the sternal notch in 20% of the cases. CONCLUSION: In patients with high thoracic fractures who require surgical decompression and stabilization, pre-operative MR scan and assessing the level of the vertebra in relation to the sternal notch can allow a low anterior cervical approach to be used thus decreasing the patient morbidity related to the surgical approach. PMID- 17354193 TI - Comparison of short and long axis methods in cardiac MR imaging and echocardiography for left ventricular function. AB - PURPOSE: The purpose of this study was to compare long axis and short axis methods in cardiac magnetic resonance imaging (MRI), and echocardiography for the evaluation of left ventricular function and mass. MATERIALS AND METHODS: The study included 15 patients with a history of myocardial infarction and 5 patients with normal ventricular function who were examined with cardiac MRI and echocardiography. Left ventricular function and mass analyses calculated with Simpson's method from short axis images were compared to the results of horizontal long axis, vertical long axis, and combined axes methods. In addition, results obtained from echocardiography were compared to the short axis method in cardiac MRI. RESULTS: In the patient group, there was no significant difference between ejection fraction calculated by modified Simpson's analysis in echocardiography and short axis imaging in cardiac MRI. In cardiac MRI, there was significant difference between ejection fractions assessed from both horizontal and vertical long axis images, and those assessed from short axis images. There was no significant difference in both patient and control groups between end diastolic volume determined from short axis and end-diastolic volume determined by horizontal long axis, vertical long axis, and combined long axes. Significant difference between the patient and control groups was observed in end-diastolic volume calculated by modified Simpson's echocardiographic method. CONCLUSION: The present study demonstrated that there were no significant advantages of simplified MRI techniques over modified Simpson's method echocardiography. Therefore, patients who cannot be evaluated by echocardiography optimally should be evaluated by short axis cine MRI sequence. PMID- 17354194 TI - Peripheral cutting balloon in the management of resistant benign ureteral and biliary strictures: long-term results. AB - PURPOSE: To report the long-term follow-up results of peripheral cutting balloon incision and dilatation (PCBID) after failed high-pressure balloon dilatation in patients with benign ureteral and biliary strictures. MATERIALS AND METHODS: The study included 9 patients (5 males and 4 females) who underwent successful PCBID procedures. Of these, 4 patients had biliary strictures; 2 of them had choledocho choledochal anastomosis after liver transplantation, one at the choledocho jejunal anastomosis, and the other at the papilla of Vater after failed endoscopic papillotomy. Of the 5 patients with ureteral strictures, 2 occurred following kidney transplantation, one after local radiation, and 2 had pelvic metastases compressing the urinary tract. The duration of follow-up, both clinical and radiological, was 24 months. RESULTS: The 9 patients who underwent successful PCBID procedures represented 82% of the original group treated by PCBID, which we reported in a previous publication. There were no periprocedural complications. The rate of primary patency, which was confirmed clinically and ultrasonographically at the end of follow- up, was 55% (5/9), and the secondary patency rate was 78% (7/9). Choledocho-choledochal restenosis occurred in 2 patients, 5 and 9 months after liver transplantation, who were treated percutaneously; one by balloon angioplasty (secondary patency for 19 months) and the other by PCBID (patency for 15 months). The remaining 2 patients (both with pelvic metastases) had restenosis 5 and 6 months postprocedure and were successfully treated by the insertion of double-J ureteral stents. CONCLUSION: PCBID is a simple and safe option for the treatment of ureteral and biliary strictures after failed high-pressure balloon dilatation, which demonstrated a two-year primary patency rate of 55% and a secondary patency rate of 78%. PMID- 17354195 TI - Wide-necked renal artery aneurysm: endovascular treatment with stent-graft. AB - Aneurysms of the renal artery are rare and have an estimated incidence of 0.09% in the general population. They may be diagnosed incidentally or during the evaluation of related symptoms. They may be followed up or treated either surgically or endovascularly. We present a successful percutaneous treatment of a renal artery aneurysm with stenosis by a stent-graft in a 55-year-old woman, who was diagnosed during the evaluation of labile hypertension. Follow-up was for 6 months. PMID- 17354196 TI - An unusual complication of carotid stenting: spontaneous rectus sheath hematoma and its endovascular management. AB - Carotid stenting has recently emerged as a potential alternative to surgical treatment. We report a case of a spontaneous rectus sheath hematoma in a patient who underwent anticoagulation therapy following carotid stenting. Computed tomography findings were consistent with active bleeding within the hematoma, and this was confirmed with selective angiography via right deep circumflex iliac artery injection. Transcatheter embolization of the right deep circumflex iliac artery with n-butyl 2-cyanoacrylate was successfully performed. To the best of our knowledge, spontaneous anterior abdominal wall hemorrhaging following carotid stenting has not been previously reported in the English language literature. PMID- 17354197 TI - Treatment of pelvic aneurysmal bone cysts in two children: selective arterial embolization as an adjunct to curettage and bone grafting. AB - Treatment options of aneurysmal bone cysts include complete resection, curettage, curettage with bone grafting, selective arterial embolization (as a primary treatment or preoperative adjuvant therapy), and percutaneous injection of fibrosing agent. Treatment in pelvic locations is difficult because of the relative inaccessibility of the lesions, the proximity of the lesions to neurovascular structures, and the vulnerability of the acetabulum. Herein, we present 2 pediatric cases of pelvic aneurysmal bone cysts successfully treated with curettage with bone grafting following preoperative selective arterial embolization. PMID- 17354198 TI - Leptin promotes the growth of Colon 38 cancer cells and interferes with the cytotoxic effect of fluorouracil in vitro. AB - INTRODUCTION: Epidemiological studies underline the fact that obesity represents a significant risk factor for the development of several cancers, one of which is cancer of the colon. Moreover, multiple recent data indicate that some adipose tissue-derived hormones may influence the growth of malignant cells. Leptin, the product of the ob gene, is one of these. However, the evidence from research is still contradictory regarding the role of leptin in colon cancer. The aim of our study was to examine the direct effect of leptin at various concentrations (from 10(-5) to 10(-12) M) when applied alone or jointly with fluorouracil (the classical cytotoxic drug for colon cancer) at two concentrations (0.25 mg/ml and 2.5 mg/ml) on the growth of murine Colon 38 cancer cells in vitro. MATERIAL AND METHODS: Colon 38 cancer cells were preincubated in RPMI 1640 medium supplemented with foetal calf serum for 24 hours. The cells were then cultured for a further 72 hours in the presence of various concentrations of the substances under examination, applied either alone or jointly. The growth of the Colon 38 cell line was assessed by a colorimetric kit based on the modified Mosmann method. RESULTS: We found that leptin increased the growth of murine Colon 38 cancer at concentrations of 10(-6), 10(-7) M and 10(-10), 10(-11), 10(-12) M. Its stimulatory effect was fairly slight, with an increase in cancer growth of 5% to 15% as compared to controls. As we expected, fluorouracil at both the concentrations examined inhibited the growth of Colon 38 cancer maximally up to 28% (2.5 mg/ml) and 34% (0.25 mg/ml) of controls, with a stronger effect obtained from higher doses. Leptin did not modulate the cytotoxic effect of fluorouracil applied at the higher concentration (2.5 mg/ml) but, unexpectedly, at concentrations of 1(-9) and 10(-10) M it heightened the cytotoxic effect of fluorouracil given at a lower concentration (0.25 mg/ml). CONCLUSIONS: These data indicate that leptin is involved in the regulation of colon cancer growth and it may even heighten the cytotoxic effect of fluorouracil. PMID- 17354199 TI - Osteoprotegerin--does it play a protective role in the pathogenesis of bone loss in obese perimenopausal women? AB - INTRODUCTION: Assessment of serum osteoprotegerin (OPG) concentrations in obese patients in comparison to healthy controls and evaluation of a possible correlation between OPG and other markers of bone turnover or calcitropic hormones. MATERIAL AND METHODS: 50 obese perimenopausal women without concomitant diseases (BMI 36.7 +/- 4.1 kg/m(2), mean age 50.4 +/- 4.9 yrs). The control group consisted of 19 healthy women (BMI 24.2 +/- 2.1 kg/m(2); mean age 53.8 +/- 5.1 yrs). In all patients serum concentration of OPG, C telopeptide of type I collagen containing the crosslinking site (CTX), osteocalcin, parathormone (PTH) and vitamin D (25-OH-D(3)) was assessed. Dual energy x-ray absorptiometry (the DXA method) of the lumbar spine and femoral neck was performed using a Lunar DPXL to measure bone marrow density (BMD). RESULTS: In obese perimenopausal women serum OPG, osteocalcin and 25-OH-D(3) levels were significantly lower, and the serum PTH level was significantly higher in comparison to healthy controls. A significantly positive correlation was found between serum OPG level and age in both obese and control subjects. CONCLUSION: The serum OPG level in obese perimenopausal women is significantly lower in comparison to healthy controls and does not correlate significantly with biochemical markers of bone turnover, calcitropic hormones and BMD. It probably cannot play a protective role in the pathogenesis of bone loss in obese perimenopausal women. PMID- 17354200 TI - [The histopathological evaluation of the local tolerance of alendronate containing medicines]. AB - INTRODUCTION: In order to be effective, treatment for osteoporosis must be long term. Unfortunately, according to clinical trials and clinical practice the most frequent cause of patient resignation from the treatment is adverse reactions to the medications. In the case of bisphosphonates they are most frequently connected with irritant impact of the drug on gastrointestinal mucosa. The aim of our study was to answer the question whether alendronate tablets coated with a thin neutral layer may protect gastrointestinal mucosa from the irritant effects of the active substance. MATERIAL AND METHODS: Three types of tablets were administered into the cheek pouches of 18 Syrian hamsters (divided into 3 experimental groups: I, II, III) i.e. regular alendronate tablets, coated alendronate tablets and placebo. The tablets were applied for 4 minutes a day on 4 consecutive days. 24 hours after the last application, the animals were sacrificed and segments of buccal tissue were taken for histopathological examination. Oral tissue reaction was assessed using the microscopic examination grading system developed by ISO. The following adverse changes of the tissue were recorded: epithelial lesions, leucocyte infiltration, vascular congestion and oedema. Later the irritation index was calculated. RESULTS: The irritation index was 11.0 (moderately irritant), 0.0 and 0.0 (none-irritant), in each group respectively. CONCLUSION: It appears that the administration of the coated alendronate tablets reduces the frequency and intensity of the local adverse events from the gastrointestinal tract. PMID- 17354201 TI - [The treatment of multinodular large non-toxic goiter using repeated doses of radioiodine (preliminary report)]. AB - INTRODUCTION: The aim of study was to establish the effectiveness of radioiodine therapy using 131I in the group of patients with multinodular large non-toxic goiter. MATERIAL AND METHODS: Therapy was undertaken in female patients disqualified from surgery due to high risk and these patients who didn't agree to surgery. Studies were performed in 7 women (age range: 62-82 yrs) with large goiters (2nd degree according to WHO classification and goiter volume assessed by USG over 100 cm(3)). Serum TSH, fT4, fT3, antithyroid antibodies (TPOAb, TgAb, TRAb) levels, urinary iodine concentration (UIE) were estimated in all patients parallel with radioiodine uptake test (after 5 and 24 hours), 131I thyroid scintigraphy and fine needle biopsy to exclude neoplasmatic transformation. These studies and therapy with 22 mCi 131I were repeated every 3 months. RESULTS: Before therapy median thyroid volume was approximately 145 cm(3) and during therapy gradually decreased to 76 cm(3) after 6 months and to 65 cm(3) after 12 months. Increase of TRAb can be a inhibiting factor of thyroid volume reduction. Other antithyroid antibodies showed marked tendency to rise but without significant correlation with radioiodine uptake and goiter reduction. After 12 months we found 2 patients with clinical and laboratory hypothyroidism. CONCLUSIONS: In some cases of multinodular large non-toxic goiter, the radioiodine therapy can be the best alternative way for L-thyroxine treatment or surgery therapy. The fractionated radioiodine therapy of multinodular large non toxic goiter is safe and effective method but continuation of nodules observation is necessary. PMID- 17354202 TI - [Effect of whole body cryotherapy on the levels of some hormones in professional soccer players]. AB - INTRODUCTION: The study was undertaken to determine blood serum concentrations of selected steroid hormones (estradiol--E(2), testosterone--T, dehydroepiandrosterone sulfate--DHEA-S) and luteinizing hormone (LH) in professional footballers subjected to whole body cryotherapy. MATERIAL AND METHODS: Twenty-two clinically healthy males, mean age 26.7 years, were studied. The subjects underwent ten sessions of whole body cryotherapy in Wroclaw-type chamber, with kinesitherapy following each session. Blood samples were collected before and two days after the treatment and the results were analyzed statistically. RESULTS: After the treatment there was a significant decrease in the concentrations of T (6.01 vs. 4.80 ng/mL, p < 0.01) and E(2) (102.3 vs. 47.5 pg/mL, p < 0.00001), but no DHEA-S and LH. The T/E(2) ratio showed a significant increase form 72.2 to 136.5 (p < 0.01). CONCLUSIONS: Whole body cryotherapy leads to a significant decrease in serum T and E(2), with no effect on LH and DHEAS levels. As a results of cryotherapy, the T/E(2) ratio was significant increased. The changes observed are probably due to cryotherapy-induced alternation in the blood supply to the skin and subcutaneous tissue, as well as to modulation of the activity of aromatase which is responsible for conversion of testosterone and androstenedione to estrogens. PMID- 17354203 TI - Metabolic syndrome in polycystic ovary syndrome. AB - Both metabolic syndrome (MS) and polycystic ovary syndrome (PCOS) are common among women. The exact prevalence of MS in women with PCOS is dependent upon the diagnostic criteria used for each. However, the frequent co-occurrence of both MS and PCOS in women is suggestive of a common aetiology. In this short review article we argue that insulin resistance, as a consequence of abdominal obesity, may represent such a common aetiology. We also review the literature on the prevalence of MS in women with PCOS and consider the impact that the particular criteria used to diagnose both MS and PCOS may have had on these estimates of prevalence. PMID- 17354204 TI - Polypeptide growth factors in gastroenteropancreatic neuroendocrine tumours. AB - Polypeptide growth factors form a potent class of extracellular signal molecules in the regulation of cellular differentiation and proliferation. Disturbances in the expression of growth factors influence the normal pathway of differentiation and lead to cellular transformation and tumour progression. Contemporary medical studies report that various growth factors such as those for platelet-derived growth factor, vascular endothelial growth factor, epidermal growth factor, hepatocyte growth factor and insulin-like growth factor are expressed in gastroenteropancreatic neuroendocrine tumours (GEP/NET). Polypeptide growth factors have great significance in the growth, progression and development of metastases by various tumours. We describe the role of growth factors in GEP/NET on the basis of the available reports of medical research. PMID- 17354205 TI - [Thyroidectomy as the last chance treatment for life threatening thyrotoxicosis. Case report]. AB - The case of 54-year old woman with severe Graves thyrotoxicosis and antithyroid drugs intolerance is presented. She was admitted to Endocrinology Department and therapy with propranolol, lithium, glucocorticoids, iodine contrast media was instituted. Then ablative dose of radioiodine was given; all these appeared to be ineffective. To avoid thyrotoxic storm thyroidectomy was undertaken. Surgical procedure was uneventful and successful. Surgical intervention should be considered in severe life-threatening cases of thyrotoxicosis. PMID- 17354206 TI - [Insulinoma--diagnosis and treatment]. AB - Insulinomas are the most common functioning endocrine tumors of pancreas. Approximately 10% are multiple, less than 10% can be malignant and 5-10% associated with the MEN-1 syndrome. Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. The aim of this lecture is to present the up-to-date information concerning the prevalence, diagnosis and treatment of insulinoma. PMID- 17354211 TI - Indian BioSpectrum awards 2006. PMID- 17354213 TI - The International Centre for Genetic Engineering and Biotechnology(ICGEB). PMID- 17354214 TI - Biosafety news: introducing EBSA--the European Biosafety Association. PMID- 17354215 TI - AchemAsia 2007 announcement: China's biotechnology industry on the upswing. PMID- 17354216 TI - Indian companies to watch in 2007. PMID- 17354217 TI - Biotech in Italy. PMID- 17354218 TI - Meeting report: the 4th International Conference on Textile Biotechnology. PMID- 17354220 TI - Hidden barriers between knowledge and behavior: the North Carolina prostate cancer screening and treatment experience. AB - BACKGROUND: Prostate cancer (PC) mortality is much greater for African American than for Caucasian men. To identify patient factors that might account for some of this disparity, men within 6 months of diagnosis were surveyed about health attitudes and behavior. METHODS: Using Rapid Identification in the North Carolina Cancer Registry, 207 African American and 348 Caucasian recently diagnosed PC patients were identified and surveyed. RESULTS: African American men were younger and less often currently married, and had lesser education, job status, and income than Caucasian men (all P < .001). African American men were at no greater distance to medical care, but had less access: poorer medical insurance coverage, more use of public clinics and emergency wards, less continuity with a primary physician, and more often omitted physician visits they felt they needed. They also expressed less trust in physicians. African American men acknowledged their greater risk of PC, accepted greater responsibility for their health, and reported more personal failures that delayed diagnosis. African American men more often requested the tests that diagnosed their cancers, which resulted more often from routinely ordered screening tests for Caucasian men. African American men expressed less interest in nontraditional treatments. CONCLUSIONS: Despite lesser education, African American men in North Carolina are aware of their increased risk of cancer, the importance of treatment, and their responsibility for their health. Obstacles to timely diagnosis and appropriate care, including greater physician distrust, appear more likely to arise from reduced access and continuity of medical care arising from their worse socioeconomic position. PMID- 17354222 TI - Involvement of PPAR gamma and E-cadherin/beta-catenin pathway in the antiproliferative effect of conjugated linoleic acid in MCF-7 cells. AB - Conjugated linoleic acid (CLA) is a naturally occurring fatty acid, which has been shown to exert beneficial effects against breast carcinogenesis. It has been reported that CLA could modulate cellular proliferation and differentiation through the activation of peroxisome proliferator-activated receptors (PPARs). Among different PPAR isotypes, PPAR gamma is involved in growth inhibition of transformed cells. Ligands of PPAR gamma are considered as potential anticancer drugs, so CLA was tested for its ability to induce PPAR gamma expression in MCF-7 breast cancer cells. The effects of CLA and of a specific synthetic PPAR gamma antagonist were evaluated on cell growth as well as on parameters responsible for cell growth regulation. We demonstrated here that CLA stimulated the expression of PPAR gamma to levels up to control and caused PPAR gamma translocation into the nucleus. Furthermore, the overexpression of PPAR gamma positively correlates with the inhibition of cell proliferation and with the modulation of ERK signaling induced by CLA; in all cases the administration of the antagonist reverted CLA effects. The PPAR-signaling pathway is connected with the beta catenin/E-cadherin pathway, thus we evaluated CLA effects on the expression and cellular distribution of these proteins, which are involved in cell adhesion and responsible for invasive behavior. The treatment with CLA determined the up regulation and the redistribution of beta-catenin and E-cadherin and the antagonist reverted only the effect on beta-catenin. These studies indicate that CLA regulates PPAR gamma expression by selectively acting as an agonist and may influence cell-cell adhesion and invasiveness of MCF-7 cells. PMID- 17354223 TI - Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium-90 labeled murine HMFG1 without improvement in overall survival. AB - This study analyzes the site of disease recurrence in ovarian cancer patients to assess the influence of a single intraperitoneal (IP) administration of yttrium 90-labeled murine monoclonal antibody HMFG1 ((90)Y-muHMFG1) on the pattern of disease recurrence. In a large phase III trial ovarian cancer patients in complete clinical remission with FIGO stage Ic-IV were randomized between standard treatment plus a single IP (90)Y-labeled muHMFG1 versus standard treatment alone after negative second-look laparoscopy. Case report forms of all patients with disease recurrence were reviewed to determine site and date of recurrent disease. In total 447 patients were included in the study with a median follow-up of 3.5 years. Relapse was seen in 104/224 in the active and 98/223 in the control arm. Significantly fewer IP (p < 0.05) and more extraperitoneal (p < 0.05) relapses occurred in the active treatment arm. Time to IP recurrence was significantly longer (p = 0.0019) and time to extraperitoneal recurrence was significantly shorter for the active treatment arm (p < 0.001). The impact of IP radioimmunotherapy on IP relapse-free survival could only be seen in the subgroup of patients with residual disease after primary surgery (HR, 0.31; 95% CI, 0.18 to 0.53; p = 0.002). Although, there is no survival benefit for IP radioimmunotherapy as consolidation treatment for epithelial ovarian cancer, we found an improved control of IP disease, that was offset by increased extraperitoneal recurrences. PMID- 17354224 TI - Meat and meat-mutagen intake, doneness preference and the risk of colorectal polyps: the Tennessee Colorectal Polyp Study. AB - Although meat intake has been fairly consistently linked to the risk of colorectal cancer, only a few studies have evaluated meat intake by doneness level and the heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) produced by high temperature cooking of meat in relation to colorectal adenomatous and hyperplastic polyps. We evaluated these associations in a large colonoscopy-based case-control study. Included in this study were participants with adenomatous polyp only (n = 573), hyperplastic polyp only (n = 256), or both adenomatous and hyperplastic polyps (n = 199), and 1,544 polyp-free controls. In addition to information related to demographic and other lifestyle factors, meat intake by cooking method and doneness preference were obtained through telephone interviews. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for the association between exposures and colorectal polyp risks. Presence of hyperplastic polyp was found to be positively associated with high consumption of total meat (p(trend) = 0.076) or red meat (p(trend) = 0.060), with an approximate 50-60% elevated risk observed in the highest vs. the lowest intake group. High intake of 2-amino-I-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo [4,5]quinoxaline (DiMeIQx) were associated with increased risk for hyperplastic polyp (p(trend) = 0.036 and 0.038, respectively). With a possible exception of the intake of total well-done meats (p(trend) = 0.055) or well-done red meats (p(trend) = 0.074) with the risk of large adenomas, no other positive association was found specifically for the risk of adenomas with any of the exposure variables aforementioned. This study provides additional support for a positive association of high intake of red meat with colorectal adenomas, and suggests that high intake of meats and meat carcinogens may also be associated with hyperplastic polyps. PMID- 17354225 TI - Aberrant regulation of argininosuccinate synthetase by TNF-alpha in human epithelial ovarian cancer. AB - The pro-inflammatory cytokine, tumour necrosis factor-alpha, TNF-alpha, is dysregulated in malignant compared with normal ovarian surface epithelium (OSE). Several epidemiological studies have associated inflammation with ovarian tumorigenesis, with TNF-alpha playing a key role in modulating invasion, angiogenesis and metastasis. Here, we show that TNF-alpha also induces expression of arate-limiting enzyme in arginine synthesis, argininosuccinate synthetase (AS), thereby linking inflammation with several arginine-dependent metabolic pathways, implicated in accelerated carcinogenesis and tumour progression. Having identified AS mRNA induction in TNF-alpha-treated IGROV-1 ovarian cancer cells, using RNA-arbitrarily primed-PCR, we then observed differential regulation of AS mRNA and protein in malignant, compared with normal, OSE cells. A cDNA cancer profiling array with matched normal ovarian and ovarian tumour samples revealed increased expression of AS mRNA in the latter. Moreover, AS protein co-localised with TNF-alpha in ovarian cancer cells, with significantly higher levels of AS in malignant compared with normal ovarian tissue. Increased co-expression of AS and TNF-alpha mRNA was also observed in 2 other epithelial tumours, non-small cell lung and stomach cancer, compared with normal corresponding tissues. In summary, high levels of AS expression, which may be required for several arginine dependent processes in cancer, including the production of nitric oxide, proline, pyrimidines and polyamines, is regulated by TNF-alpha and may provide an important molecular pathway linking inflammation and metabolism to ovarian tumorigenesis. PMID- 17354226 TI - Assessment of prognosis with the total illness burden index for prostate cancer: aiding clinicians in treatment choice. AB - BACKGROUND: Among the most pressing challenges that face physicians who care for men with prostate cancer is evaluating the patient's potential for benefiting from treatment. Because prostate cancer often follows an indolent course, the presence and severity of comorbidities may influence the decision to treat the patient aggressively. The authors adapted the Total Illness Burden Index (TIBI) for use in decision-making among men with prostate cancer at the time of the visit. METHODS: An observational study was performed of 2894 participants in the Cancer of the Prostate Strategic Urologic Research Endeavor, a national disease registry of men with prostate cancer, to examine how well the adapted TIBI for prostate cancer (TIBI-CaP) predicted mortality over the subsequent 3.5 years and health-related quality of life over the subsequent 6 months. RESULTS: The men who had the highest global TIBI-CaP scores were 13 times more likely to die of causes other than prostate cancer over a 3.5-year period than the men who had the lowest scores (hazard ratio, 13.1, 95% confidence interval, 6.3-27.4) after controlling for age, education, income, and race/ethnicity. Patients who had the highest TIBI CaP scores had 44% mortality compared with 4.9% mortality for patients who had the lowest scores. Demographic variables explained 16% of the variance in future physical function; TIBI-CaP scores explained an additional 19% of the variance. CONCLUSIONS: The TIBI-CaP, a patient-reported measure of comorbidity, identified patients at high risk for nonprostate cancer mortality. It predicted both mortality and future quality of life. The TIBI-CaP may aid physicians and patients in making appropriate treatment decisions. PMID- 17354227 TI - Identifying breast cancer patients most likely to benefit from aromatase inhibitor therapy after adjuvant tamoxifen. PMID- 17354228 TI - Kallikrein 7 enhances pancreatic cancer cell invasion by shedding E-cadherin. AB - BACKGROUND: Pancreatic cancer (PaC) is characterized by local invasion and early metastasis. Serine proteases have been associated with invasion and metastasis of many cancers due to their ability to degrade extracellular matrix (ECM) proteins and to activate other proteases; thus, the serine proteases expressed in PaC were investigated. METHODS: An expression profile of serine proteases was generated from both normal and malignant pancreatic tissues using a polymerase chain reaction (PCR)-based screen and differential expression of kallikrein 7 was examined by reverse-transcriptase PCR (RT-PCR) and immunohistochemical analyses. The ability of human kallikrein 7 (hK7) to cleave the epithelial cell adhesion molecule E-cadherin was tested in vitro using both recombinant E-cadherin and BxPC-3 cells and the effects of hK7 proteolytic activity on pancreatic cell invasion and aggregation were examined. RESULTS: Expression profiling revealed that kallikrein 7 (KLK7) was overexpressed in pancreatic adenocarcinomas and its differential expression was confirmed by RT-PCR analysis. hK7 was observed in neoplastic cells of all tumors examined with moderate-to-intense staining in 70% of tumors examined (16/23). In contrast, only 15% of nonmalignant tissue specimens (2/13) displayed moderate hK7 staining, whereas the remaining specimens yielded weak, if any, immunoreactivity. Using in vitro assays, hK7 was shown to cleave E-cadherin and the soluble E-cadherin fragment produced significantly enhanced Panc-1 cell invasion through ECM proteins with a corresponding reduction in Panc-1 cell aggregation. CONCLUSIONS: These results suggest that aberrant expression of KLK7 plays an important role in PaC and provides novel insight into the effects of elevated hK7 proteinase activity in this, and perhaps other, adenocarcinomas. PMID- 17354229 TI - Impact of epidermal growth factor receptor (EGFR) kinase mutations, EGFR gene amplifications, and KRAS mutations on survival of pancreatic adenocarcinoma. AB - BACKGROUND: Erlotinib, in combination with gemcitabine, has shown clinical benefits in pancreatic adenocarcinoma patients. The presence of EGFR mutations and increased EGFR copy numbers in pancreatic adenocarcinoma was explored. METHODS: Sixty-six pancreatic cancer patients were included in the analysis. The EGFR mutation was analyzed by DNA sequencing of exons 18-21 in the tyrosine kinase domain. KRAS mutation was analyzed by sequencing codons 12, 13, and 61. Quantitative real-time polymerase chain reaction was performed to analyze the copy number of EGFR. RESULTS: In the current study the EGFR mutation was harbored in only 1 (1.5%) of the 66 inoperable or metastatic pancreatic adenocarcinoma patients. Amino acid substitution was detected in exon 20 of the EGFR gene. Increased EGFR copy numbers (> or =3.0 per cell) were detected in 26 (41%) patients. There was only 1 patient, who had a highly increased EGFR copy number (> or =6.0 per cell), who died, 2.1 months from the date of diagnosis. The EGFR amplification did not significantly influence survival in pancreatic adenocarcinoma patients (P = .935). Thirty-two (49%) of the 65 pancreatic adenocarcinomas examined harbored a point mutation in codons 12 (n = 31) and 61 (n = 1) of the KRAS gene. The presence of a point mutation in codon 12 adversely influenced survival of pancreatic cancer patients (P = .030). CONCLUSIONS: The incidence of somatic mutations in the tyrosine kinase domains of EGFR was very low and the increased gene copy number of EGFR did not significantly influence survival. PMID- 17354230 TI - Inhibitory effect of 4-methylesculetin on hyaluronan synthesis slows the development of human pancreatic cancer in vitro and in nude mice. AB - We report the inhibitory effect of 4-methylesculetin (ME), a 4 methylumbelliferone derivative, on hyaluronan (HA) synthesis by pancreatic cancer cells, and its resulting anticancer action. First, HA in cell culture was analyzed using competitive inhibition with hyaluronic acid-binding protein (HABP) to study HA synthesis by the human pancreatic cancer cell line KP1-NK, and cell surface HA was visualized using a particle-exclusion assay to study the synthesis of extracellular matrix HA. We also analyzed the inhibitory effect of ME on cell adhesion and invasion, which play a role in the invasion, growth and metastasis of human pancreatic cancer. Furthermore, we examined HA in human pancreatic cancer cells transplanted into the hypodermis of nude mice to study the inhibitory effect of ME on HA synthesis. Moreover, pancreatic cancer cells were also transplanted into the abdomen of nude mice to study whether ME would have the potential to prolong the survival of patients with end-stage pancreatic cancer. ME at 10 muM did not inhibit the growth of human pancreatic cancer cells, but inhibited HA synthesis in cell culture by 40%, adhesion by 44% and invasion by 40%. ME inhibited the proliferation of subcutaneous tumors and HA synthesis (by 50%) of pancreatic cancer transplanted into the hypodermis of nude mice. ME also prolonged the survival time of nude mice bearing abdominally transplanted pancreatic cancer cells. ME inhibited pancreatic cancer growth and metastasis by inhibition of HA synthesis. These results suggest that ME may prolong the survival time of patients with end-stage pancreatic cancer. PMID- 17354231 TI - Chromosomal 20q gain in the DNA diploid component of aneuploid colorectal carcinomas. AB - The order of appearance of different genetic aberrations during the shift from diploidy/near-diploidy to aneuploidy in colorectal cancers is not yet clear. We studied genetic alterations in flow cytometrically-sorted DNA diploid and corresponding aneuploid epithelial cell populations from each of 20 colorectal tumors using comparative genomic hybridization, FISH, and PCR. Analysis of the 19 cases in which aberrations were found in the flow-sorted diploid population indicated that large-scale aneuploidization in colorectal cancer was preceded by amplification of oncogene(s) localized to chromosome 20q13.2 and by KRAS mutations, but not by TP53 deletions or losses of large chromosomal regions such as 4q, 8p and 18q. PMID- 17354232 TI - Centralization of care for patients with advanced-stage ovarian cancer: a cost effectiveness analysis. AB - BACKGROUND: The objective of this study was to evaluate the cost-effectiveness of centralized referral of patients with advanced-stage epithelial ovarian cancer who underwent primary cytoreductive surgery and adjuvant chemotherapy. METHODS: A decision-analysis model was used to compare 2 referral strategies for patients with advanced-stage ovarian cancer: 1) referral to an expert center, with a rate of optimal primary cytoreduction of 75% and utilization of combined intraperitoneal and intravenous adjuvant chemotherapy, and 2) referral to a less experienced center, with a rate of optimal primary cytoreduction of 25% and adjuvant treatment that consisted predominantly of intravenous chemotherapy alone. The cost-effectiveness of each strategy was evaluated from the perspective of society. RESULTS: A cost-effectiveness analysis revealed that the strategy of expert center referral had an overall cost per patient of $50,652 and had an effectiveness of 5.12 quality-adjusted life years (QALYs). The strategy of referral to a less experienced center carried an overall cost of $39,957 and had an effectiveness of 2.33 QALYs. The expert center strategy was associated with an additional 2.78 QALYs at an incremental cost of $10,695 but was more cost effective, with a cost-effective ratio of $9893 per QALY compared with $17,149 per QALY for the less experienced center referral strategy. Sensitivity analyses and a Monte Carlo simulation confirmed the robustness of the model. CONCLUSIONS: According to results from the decision-analysis model, centralized referral of patients with ovarian cancer to an expert center was a cost-effective healthcare strategy and represents a paradigm for quality cancer care, delivering superior patient outcomes at an economically affordable cost. Increased efforts to align current patterns of care with a universal strategy of centralized expert referral are warranted. PMID- 17354233 TI - Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression. AB - This study consisted of 2 aims: (i) to determine genes associated with hepatocellular carcinoma (HCC) by microarray analysis; and (ii) to evaluate the clinicopathological significance of human ubiquitin-conjugating enzyme E2C (Ube2c) found to be overexpressed in HCC from microarray analysis. Laser microdissection and cDNA-microarray were performed to identify genes associated with HCC. We then focused on the Ube2c gene. Using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR), Ube2c expression status and clinicopathological significance were studied in 65 clinical HCC samples. A number of genes upregulated in HCC cells compared to noncancerous liver cells were identified, one of which was the Ube2c gene. Ube2c gene expression in the cancer tissue was higher than in the corresponding noncancerous tissue in 62 of the 65 cases (95.4%, p < 0.01). Tumors with high Ube2c expression showed higher frequencies of tumor invasion to capsular formation (fc-inf), invasion to portal vein (vp) and tumor de-differentiation (p < 0.05). Patients with high Ube2c expression also showed significantly worse disease-free survival rates than those with low Ube2c expression (p < 0.01). In addition, Ube2c expression was found to be an independent prognostic factor for disease-free survival rate in multivariate analysis. We identified differentially expressed genes between HCC and normal liver tissues. Of those, the Ube2c gene appeared to be associated with HCC progression, and may be useful as a prognostic indicator for HCC patients. PMID- 17354234 TI - Expression of NF-kappaB parallels COX-2 expression in oral precancer and cancer: association with smokeless tobacco. AB - Nuclear Factor-kappaB (NF-kappaB) activation and COX-2 overexpression have been reported in head and neck cancer, but the relationship between these proteins remains to be investigated. To determine the relationship between NF-kappaB and COX-2 in Smokeless Tobacco (ST) associated oral tumorigenesis, we performed immunohistochemistry in serial sections from 107 OSCCs, 78 oral precancerous lesions (OPLs) (58 hyperplasias, 20 dysplasias) and 15 histologically normal oral tissues and correlated with clinicopathological data. Significant increase in NF kappaB and COX-2 immunopositivity was observed from normal oral mucosa to OPLs to OSCCs (p = 0.009 and p = 0.002 respectively). Upregulation of NF-kappaB and COX-2 was observed as early as in hyperplasia [p = 0.006; OR = 6.1 and p = 0.003; OR = 7.6, respectively]. Expression of both proteins was found to be significantly associated in OPLs (p = 0.000; OR = 12.6) and OSCCs (p = 0.001; OR = 4.0). Intriguingly, khaini consumption correlated with NF-kappaB immunopositivity in OPLs (p = 0.05, OR = 3.8) and OSCCs (p = 0.01, OR = 3.4) and with COX-2 expression in OPLs (p = 0.03; OR = 4.3). In vitro experimental system of ST associated oral carcinogenesis was used to demonstrate ST (khaini) and NNK mediated activation of NF-kappaB and COX-2, supporting the clinical data. In conclusion, this study demonstrates correlation between over expression of NF kappaB and COX-2 in early precancerous stages of development of oral cancer and sustained elevation down the tumorigenic pathway, underscoring their potential as targets for early intervention. In vitro studies demonstrated that NNK may be one of the carcinogenic components of ST (khaini) inducing activation of NF-kappaB and COX-2 in oral precancer and cancer cells, suggesting plausible role in ST induced oral carcinogenesis. PMID- 17354235 TI - Six-month natural history of oral versus cervical human papillomavirus infection. AB - Human papillomavirus (HPV) infection is etiologically associated with a subset of oral cancers, and yet, the natural history of oral HPV infection remains unexplored. The feasibility of studying oral HPV natural history was evaluated by collecting oral rinse samples on 2 occasions at a 6-month interval from 136 HIV positive and 63 HIV-negative participants. Cervical vaginal lavage samples were concurrently collected for comparison. HPV genomic DNA was detected in oral and cervical samples by consensus primer PCR and type-specified for 37 HPV types. The six-month cumulative prevalence of oral HPV infection was significantly less than for cervical infection (p < 0.0001). HIV-positive women were more likely than HIV negative women to have an oral (33 vs. 15%, p = 0.016) or cervical (78 vs. 51%, p < 0.001) infection detected. Oral HPV infections detected at baseline were as likely as cervical infections to persist to 6 months among HIV-negative (60% vs. 51%, p = 0.70) and HIV-positive (55% vs. 63%, p = 0.27) women. Factors that independently elevated odds for oral HPV persistence differed from cervical infection and included current smoking (OR = 8, 95% CI = 1.3-53), age above 44 years (OR = 20, 95% CI = 4.1-83), CD4 < 500 (OR = 6, 95% CI = 1.1-26), use of HAART therapy (OR = 12, 95% CI = 1.0-156), and time on HAART therapy (trend p = 0.04). The rate of oral HPV infections newly detected at follow-up was significantly lower than cervical infection among HIV-positive (p < 0.001) and HIV-negative women (p < 0.001). Our study not only demonstrates that it is feasible to study the natural history of oral HPV infection with oral rinse sampling, but also indicates that oral and cervical HPV natural history may differ. PMID- 17354236 TI - Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A. AB - The MDM2-antagonist Nutlin 3A can efficiently induce apoptosis in osteosarcoma cell lines with amplified MDM2. However, Nutlin-based therapy could be even more important in more common sarcoma types where this aberration is frequent. The well- and de-differentiated liposarcomas have complex marker chromosomes, consistently including multiple copies of the MDM2 locus. Since amplification seems to be a primary aberration in these tumors, whereas amplification in osteosarcoma generally is a progression marker, the underlying biological mechanisms may be different. We have therefore investigated the molecular response to Nutlin treatment in several liposarcoma cell lines with such markers, as well as a panel of other sarcoma cell lines. We report that Nutlin efficiently stabilized p53 and induced downstream p53 dependent transcription and apoptosis in liposarcoma cells with amplified MDM2 in vitro. Some effect of Nutlin was also observed on cell lines without amplified MDM2 but with wt TP53, but no apoptosis was induced. The MDM4 protein, reported to interfere with the reactivation of p53, was undetectable in cells with amplified MDM2. Thus, Nutlin represents a promising new therapeutic principle for the treatment of an increasing group of sarcomas. PMID- 17354237 TI - Prognosis of adenocarcinoma of the uterine cervix: p53 expression correlates with higher incidence of mortality. AB - We investigated the significance of prognostic markers-estrogen receptor, progesterone receptor, p53, MIB-1 and bcl-2 - in adenocarcinoma of the uterine cervix. In 101 patients with primary cervical adenocarcinoma, treated from 1989 to 2000, we evaluated clinical parameters in relation to these prognostic markers. Mean age of patients was 45 years. Seventy eight percent of the patients were in FIGO stage I, 16% stage II, 7% stage III and IV. estrogen receptor, progesterone receptor, p53 and bcl-2 immunoreactivity was scored as 0 (up to 5% positive cells), 1+ (5-25% of cells positive), 2+ (26-50% of cells positive), 3+ (51-75% of cells positive) or 4+ (>76% of cells positive). MIB-1 was scored in 10 categories: 0-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, 91-100. The overall survival rate was 67%. Survival was not influenced by estrogen receptor, progesterone receptor, MIB-1, or bcl-2 strongly positive staining. Only p53 showed significant influence on survival, even when adjusted for stage or tumor grade. In conclusion, it does not seems useful to determine estrogen receptor, progesterone receptor, MIB-1 or bcl-2 in cervical adenocarcinomas as an indication of prognosis: survival is not influenced by presence or absence. However, if p53 staining is strongly positive survival is significantly worse than in tumors scored as negative or weak positive. PMID- 17354238 TI - Treatment of implanted mammary tumors with recombinant vesicular stomatitis virus targeted to Her2/neu. AB - Vesicular stomatitis virus (VSV) is being developed for cancer therapy. We have created a recombinant replicating VSV (rrVSV) that targeted to Her2/neu expressing breast cancer cells and expresses mouse GM-CSF. We now tested the efficacy of this rrVSV in the treatment of peritoneal tumor implants of D2F2/E2 cells, a BALB/c mouse mammary tumor cell line, which was stably transfected to express Her2/neu. Mice were treated 1 day following tumor implantation with either 2 x 10(8) infectious doses rrVSV or conditioned media (CM). All control animals developed massive peritoneal tumor with a median survival of 16 days. Nine of 10 rrVSV treated mice survived long term with no evidence of tumor. rrVSV had much less efficacy in treating implants of the parent D2F2 cells that did not express Her2/neu. The median survival was 13.5 days in mice treated with CM and 21 days in those treated with rrVSV. There was one long term survivor in the rrVSV treated group. None of the rrVSV treated animals showed evidence of viral toxicity. Three of 7 long term survivors did not develop tumor when rechallenged first with D2F2/E2 and then with D2F2 cells. Both successful therapy and resistance to rechallenge were T-cell dependent. These studies demonstrate that targeted rrVSV eliminated peritoneal implants of Her2/neu expressing tumor and elicited an anti-tumor T-cell immunologic response. PMID- 17354239 TI - Breast cancer risk and erythrocyte compositions of n-3 highly unsaturated fatty acids in Japanese. AB - Dietary intake of fish rich in n-3 highly unsaturated fatty acids (HUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been proposed to decrease cancer risk. In contrast to results from laboratory studies, however, protective effects for breast cancer have proved equivocal in epidemiological studies. In the present case-control study, we examined associations between breast cancer risk and fatty acid compositions in erythrocyte membranes as biomarkers for those intakes. Dietary information and blood samples were collected from 103 incident breast cancer cases and 309 non-cancer controls (matched by age and season) and erythrocyte fatty acids were measured using accelerated solvent extraction and gas-liquid chromatography. Dietary intake of n 3 HUFAs demonstrated a negative association with risk (the highest to the lowest tertile, odds ratio (OR), 0.51; 95% confidence interval (CI), 0.27-0.98; p(trend)<0.05), but there was no association with those of saturated fatty acids (SFAs) and meat. Moreover, risk was inversely associated with erythrocyte compositions of EPA (OR, 0.27; 95% CI, 0.14-0.53; p(trend)<0.0001), DHA (OR, 0.06; 95% CI, 0.02-0.16; p(trend)<0.0001) and n-3 HUFAs (OR, 0.11; 95% CI, 0.05 0.24; p(trend)<0.0001), and positively with that of SFAs (OR, 12.29; 95% CI, 4.94 30.57; p(trend)<0.0001) and the ratio of SFAs/n-3 HUFAs (OR, 14.65; 95% CI, 5.67 37.82; p(trend)<0.0001). In conclusion, we showed that erythrocyte compositions of specific fatty acids derived from fish intake, as biomarkers, are associated with lower risk of breast cancer, but further studies are needed to investigate mechanisms linked to the etiology. PMID- 17354240 TI - Erionite and asbestos differently cause transformation of human mesothelial cells. AB - Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection. Nevertheless, several cases of MM were associated with environmental exposure to erionite in Turkey, where SV40 was never isolated in MM specimens. We show here that erionite is poorly cytotoxic, induces proliferating signals and high growth rate in human mesothelial cells (HMC). Long term exposure to erionite, but not to asbestos fibers, transforms HMC in vitro, regardless of the presence of SV40 sequences, leading to foci formation in cultured monolayers. Cells derived from foci display constitutive activation of Akt, NF-kappaB and Erk1/2, show prolonged survival and a deregulated cell cycle, involving cyclin D1 and E overexpression. Our results reveal that erionite is able per se to turn HMC into transformed highly proliferating cells and disclose the carcinogenic properties of erionite, prompting for a careful evaluation of environmental exposure to these fibers. The genetic predisposition to the effect of erionite is a separate subject for investigation. PMID- 17354241 TI - Risk of high-grade cervical intra-epithelial neoplasia based on cytology and high risk HPV testing at baseline and at 6-months. AB - Adding a test for high-risk human papillomavirus (hrHPV) to cytological screening enhances the detection of high-grade cervical intraepithelial neoplasia (>or=CIN2), but data are required that enable long-term evaluation of screening. We investigated the >or=CIN2 risk for women participating in population-based screening as a function of hrHPV and cytology testing results at baseline and at 6 months. We included 2,193 women aged 30-60 years participating in a population based screening trial who received colposcopy or a repeat testing advice at baseline. The main endpoint was histologically confirmed >or=CIN2 diagnosed within 36 months. hrHPV testing was more sensitive than cytology for >or=CIN2 (relative sensitivity 1.4, 95%CI: 1.3-1.5; absolute sensitivity 94.1 and 68.0%, respectively). The 18-month >or=CIN2 risks in women with a hrHPV-positive smear and in women with abnormal cytology were similar (relative risk 0.9, 95%CI: 0.8 1.1). Women with HPV16 and/or HPV18 had a higher >or=CIN2 risk than other hrHPV positive women irrespective of the cytological grade. Repeat testing showed that both cytological regression and viral clearance were strongly associated with a decrease in >or=CIN2 risk. Notably, women who had a double negative repeat test at 6 months had a >or=CIN2 risk of only 0.2% (95%CI: 0.0-1.1) and hrHPV-negative women with baseline borderline or mild dyskaryosis and normal cytology at 6 months had a >or=CIN2 risk of 0% (95%CI: 0.0-0.8). Using hrHPV and/or cytology testing, risk of >or=CIN2 can be assessed more accurately by repeat testing than single visit testing. Hence, when hrHPV testing is implemented, patient management with repeat testing is a promising strategy to control the number of referrals for colposcopy. PMID- 17354242 TI - Large mycotic aneurysm of the peroneal artery. AB - We describe the case of a 37-year-old patient with mycotic aneurysm of the right peroneal artery associated with episodes of endocarditis. There are only 7 cases of mycotic aneurysms of the crural arteries reported in the literature. To the best of our knowledge, this is the first reported case of a mycotic aneurysm of the peroneal artery in an adult. PMID- 17354243 TI - Echocardiographic aspects of hiatal hernia: A review. AB - It was realized 20 years ago that the sonographic appearance of a diaphragmatic hernia could simulate a left atrial mass. Many papers have appeared on this topic since then, but they mainly consist of single case reports. Clinical symptoms due to cardiac compression by the hernia are uncommon but may occur if the hernia is very large; such patients have presented with episodes of syncope or dyspnea, typically after a large meal. Sonographers, cardiologists, gastroenterologists, and internists are generally not yet aware that sonographic presentations can be varied and are often perplexing. These include the combination of hiatal hernia with gastroesophageal reflux demonstrable in the subcostal view, and hiatal hernia in patients with ascites. PMID- 17354244 TI - Antenatal diagnosis of double outlet of right ventricle without extracardiac anomaly: a report of 4 cases. AB - Four fetuses were diagnosed antenatally with double outlet of right ventricle (DORV) at 17, 20, 26, and 28 weeks' gestation, respectively, using 2-dimensional sonography. Chromosome study was normal in all 4 cases, and there were no extracardiac abnormalities. The sonographic diagnoses were based on the following findings: (1) arising of the 2 great vessels predominantly from the right ventricle; (2) the presence of bilateral coni; and (3) parallel direction of the 2 vessels rather than the normal perpendicular course. Two cases were terminated electively with postnatal autopsy confirmation; the other 2 cases were closely monitored throughout pregnancy and underwent normal vaginal delivery at term and subsequent surgical correction with good outcome. In conclusion, DORV can be readily diagnosed in utero by checking outflow tract even without 3-dimensional sonography and in the absence of obvious risk for congenital heart defects. PMID- 17354245 TI - Diffuse leukoencephalopathy: unusual sonographic finding in an infant with mitochondrial disease. AB - Several mitochondrial diseases are known to occasionally involve the cerebral white matter, but in these cases the major findings are involved in the basal ganglia and brainstem. We report a case of diffuse white matter involvement in an infant with mitochondrial disease that was diagnosed via mitochondrial DNA analysis. Mitochondrial disease should be considered in the diagnosis of diffuse leukoencephalopathy in infancy. PMID- 17354246 TI - Splenic focal lesions as manifestation of sarcoidosis: Characterization with contrast-enhanced sonography. AB - We report the case of a 74-year-old woman with elevated liver enzyme levels in whom abdominal sonographic examination revealed a diffusely heterogeneous liver parenchyma and multiple hypoechoic subcentimetric splenic nodules. Contrast enhanced sonography (CEUS) revealed that the splenic focal lesions did not enhance. CT examination revealed a low-density, multinodular pattern both in the liver and in the spleen. Core biopsy of 1 hepatic nodule revealed noncaseating epithelioid cell granuloma, and the patient was diagnosed with systemic sarcoidosis. CEUS has shown to be useful in the diagnosis of focal hepatic lesions, but studies referring to splenic lesions are lacking. PMID- 17354247 TI - Phlegmasia cerulea dolens. AB - Phlegmasia dolens is a rare form of massive venous thrombosis of the lower extremities that is associated with a high degree of morbidity, including venous gangrene, compartment type syndrome, and arterial compromise. We report the sonographic findings in a patient who presented with phlegmasia dolens. PMID- 17354248 TI - Preoperative localization of parathyroid adenoma with sonography and 99mTc sestamibi scintigraphy in primary hyperparathyroidism. AB - PURPOSE: To evaluate the sensitivity, specificity, and usefulness of dual-phase 99mTc-Sestamibi scintigraphy (SS) and sonography (US) of the neck, alone and in combination, as noninvasive adenoma localizing procedures in patients with primary hyperparathyroidism prior to parathyroidectomy. METHODS: We retrospectively analyzed the charts of 79 patients with parathyroid (PT) adenomas and confirmed diagnosis of hyperparathyroidism who were evaluated with SS and US prior to successful parathyroidectomy. RESULTS: Ninety-three adenomas were removed during bilateral neck exploration. SS alone showed a sensitivity of 76% and a specificity of 79% compared with 89% and 75%, respectively, for US performed after SS on the same day. Combination of the 2 procedures yielded a sensitivity of 89% and a specificity of 90%, with 22% discordant results. The differences in sensitivity and specificity between the 2 techniques alone or in combination were not statistically significant. CONCLUSIONS: No benefit was gained from using both SS and US for the preoperative localization of PT adenomas in patients with primary hyperparathyroidism. Each technique can be negatively affected by thyroid enlargement and nodularity. US, when performed by a skilled operator, is a reliable tool for PT adenoma localization. If the US findings are inconclusive, SS should be used. PMID- 17354249 TI - Abdominal cocoon. AB - Abdominal cocoon is a rare cause of small intestinal obstruction observed in young females in tropical regions. It manifests by forming a membrane that typically encases the small bowel loops, leading to mechanical obstruction. Preoperative diagnosis is difficult and is usually established during laparotomy. We report a case of abdominal cocoon in a young woman diagnosed on abdominal sonography. PMID- 17354250 TI - Pentalogy of Cantrell: sonographic assessment. AB - Pentalogy of Cantrell is a rare thoraco-abdominal disruption with a variable association of abdominal wall, diaphragm, pericardium, sternum, and heart defects. Diagnosis is feasible on antenatal sonography. However, because prognosis depends on the extent of the defect, anatomic assessment is crucial for optimal parental counseling and decision-making regarding the outcome of pregnancy. We report the use of 2-dimensional and 3-dimensional sonography in the diagnosis of pentalogy of Cantrell. PMID- 17354251 TI - Sonographic diagnosis of a round ligament cyst in the inguinal area. AB - We report a case of a 37-year-old female with a mesothelial cyst of the round ligament presenting as a palpable mass. The mass appeared sonographically as a fusiform structure with several cystic anechoic areas and was misdiagnosed preoperatively as herniation of the right ovary. PMID- 17354252 TI - Prenatal sonographic diagnosis of an extensive fetal axillary hemangiolymphangioma. AB - Hemangiolymphangioma (HL) is an extremely rare malformation of both the lymphatic and blood vessels. We present a case of fetal axillary HL that was diagnosed sonographically at 36 weeks' gestation. Sonographic examination revealed a large, multilocular, cystic mass consistent with lymphangioma. At birth, a giant hemangioma was noticed involving the right hemitruncus. Based on clinical and sonographic findings, a diagnosis of HL was made. Surgical treatment was considered but was refused by the parents. The neonate died at 14 days of age, possibly due to an intralesional hemorrhage. PMID- 17354253 TI - Clinical trial registration. PMID- 17354254 TI - DNA adducts in granulocytes of hospital workers exposed to ethylene oxide. AB - BACKGROUND: Ethylene oxide (EtO), an important industrial chemical intermediate and sterilant, is classified as a human carcinogen. Occupational EtO exposure in many countries is regulated at 1 ppm (8-hr TWA), but levels of EtO-DNA adducts in humans with low occupational EtO exposures have not been reported. METHODS: We examined the formation of N7-(2'-hydroxyethyl)guanine (N7-HEG), a major DNA adduct of EtO, in 58 EtO-exposed sterilizer operators and six nonexposed workers from ten hospitals. N7-HEG was quantified in granulocyte DNA (0.1-11.5 microg) by a highly sensitive and specific gas chromatography-electron capture-mass spectrometry method. Cumulative exposure to EtO (ppm-hour) was estimated during the 4-month period before the collection of blood samples. RESULTS: There was considerable inter-individual variability in the levels of N7-HEG with a range of 1.6-241.3 adducts/10(7) nucleotides. The mean levels in the nonexposed, low (< or =32 ppm-hour), and high (>32 ppm-hour) EtO-exposure groups were 3.8, 16.3, and 20.3 adducts/10(7) nucleotides, respectively, after the adjustment for cigarette smoking and other potential confounders, but the differences were not statistically significant. CONCLUSIONS: This study has demonstrated for the first time, detectable levels of N7-HEG adducts in granulocytes of hospital workers with EtO exposures at levels less than the current U.S. standard of 1 ppm (8-hr TWA). A nonsignificant increase in adduct levels with increasing EtO exposure indicates that further studies of EtO-exposed workers are needed to clarify the relationship between EtO exposure and N7-HEG adduct formation. PMID- 17354255 TI - The new publication policy of Neurourology and Urodynamics. PMID- 17354256 TI - Selective upregulation and amplification of the lysyl oxidase like-4 (LOXL4) gene in head and neck squamous cell carcinoma. AB - Members of the lysyl oxidase family (LOX) are copper and lysyl-tyrosine quinone cofactor-containing amine oxidases that are important for the assembly and maintenance of components of the extracellular matrix. Our previous results demonstrated that a novel member, LOXL4, is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. Results of the current study showed overexpression of the LOXL4 transcript in 74% (46 of 62) of invasive HNSCC tumours and 90% of both primary and metastatic HNSCC cell lines. Significant correlation was found between LOXL4 expression and local lymph node metastases versus primary tumour types (p<0.01) and higher tumour stages (p<0.01). Immunocytochemistry demonstrated cellular overexpression of the LOXL4 protein that correlated with the increased mRNA transcription in HNSCC cells. HNSCC cell lines displayed in significant subset of nuclei increased copies of the LOX4 gene locus on chromosome 10q24, demonstrated by fluorescence in situ hybridization (FISH). Extensive metaphase cytogenetic analysis was performed on UTSCC19A cells, identifying an isochromosome i(10)(q10). Taken together, these results highlight LOXL4 expression as a distinctive trait and suggest a functional role for LOXL4 in the molecular pathogenesis of invasive head and neck carcinomas. PMID- 17354257 TI - Glycemic control is related to the severity of impaired thermal sensations in type 2 diabetes. AB - BACKGROUND: Small-fibre sensory neuropathy of diabetes presenting as impaired thermal sensations is associated with ominous consequences, such as foot ulcer and amputation, but there is a lack of systematic studies on its occurrence in large cohorts. We investigated (1) the impact of glycemic control on thermal thresholds, (2) the frequencies and patterns of sensory deficits, and (3) the contribution of sensory nerve abnormalities to neuropathic symptoms. METHODS: Quantitative sensory testing and nerve conduction studies were performed to measure warm and cold thresholds of extremities, and amplitudes of nerve action potentials on 498 type 2 diabetic patients and 434 control subjects with similar age and gender distributions, enrolled during the same period. RESULTS: The diabetic patients had higher thermal thresholds than control subjects (p < 0.0001). Thermal thresholds of the lower and upper extremities were linearly correlated with HbA1C on multiple linear regression analysis (p < 0.01). By the multivariate logistic regression analysis, HbA(1C) and age were the most important risk factors independently associated with elevated thermal thresholds (p < 0.01). Elevated warm threshold in the big toe was the most frequent abnormality (60.2%) compared to abnormal cold threshold in the big toe (39.6%) and abnormal sural nerves on nerve conduction studies (12.9%). Elevated thermal thresholds were risk factors for neuropathic symptoms independent of HbA(1C). CONCLUSION: Small-fibre neuropathy with the impairment of thermal sensations is the most frequent sensory deficit in diabetes, and HbA1C is significantly associated with the elevated thermal thresholds. PMID- 17354258 TI - The relationship of the methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy. AB - BACKGROUND: Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C > T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examine the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy. METHODS: DNA was extracted from peripheral leukocytes of the subjects. Genotyping of the MTHFR C677T polymorphism for all individuals was performed by melting curve analysis of the generated amplicons after real-time online PCR. RESULTS: This genotype distribution did not differ between control subjects and type 2 diabetic patients in which 6.8% were TT, 43.7% were CT and 49.5% were CC (chi2 = 0.201, p > 0.05). The frequency of the mutant T allele was 23.4% in diabetic patients with nephropathy versus 33.0% in those without nephropathy. The genotype frequencies were TT, 2.1%; CT, 46.6%; CC, 55.3% in diabetic patients with nephropathy versus TT, 10.7%; CT, 44.6%; CC, 44.6% in those without nephropathy. CONCLUSIONS: The MTHFR genotype and allele frequencies were not different between diabetic patients with and without nephropathy (chi2 = 3, 386, p > 0.005; chi2 = 2.320, p > 0.005, respectively). Therefore, we conclude that the MTHFR gene polymorphism is not associated with the development of diabetic nephropathy in Turkish type 2 diabetic patients. PMID- 17354259 TI - Genetic variation in hepatic glucose-6-phosphatase system genes in cases of sudden infant death syndrome. AB - Genetic deficiencies of the hepatic glucose-6-phosphatase system, either of the enzyme (G6PC1) or of the glucose-6-phosphate transporter (G6PT1), result in fasting hypoglycaemia. Low hepatic G6PC1 activities were previously reported in a few term sudden infant death syndrome (SIDS) infants and assumed to be due to G6PC1 genetic deficiencies. In preterm infants, failures of postnatal activation of G6PC1 expression suggest disordered development as a novel cause of decreased G6PC1 activity in SIDS. G6PC1 and G6PT1 functional and mutational analysis was investigated in SIDS and non-SIDS infants. G6PC1 hepatic activity was abnormally low in 98 SIDS (preterm, n=13; term, n=85), and non-SIDS preterm infants (n=35) compared to term non-SIDS infants (n=29) and adults (n=9). Mean glycogen levels were elevated, except in term non-SIDS infants. A novel G6PT1 promoter polymorphism, 259C --> T was found; the - 259*T allele frequency was greater in term SIDS infants (n=140) than in term control infants (n=119) and preterm SIDS infants (n=30). Heterozygous and homozygous prevalence of 259C --> T was 38.6% and 7.1%, respectively, in term SIDS infants. In cell-based expression systems, the presence of - 259T in the promoter decreased basal luciferase activity by 3.2 fold compared to - 259C. Glucose-6-phosphatase latency in hepatic microsomes was elevated (indicating decreased G6PT1 function) in heterozygous and homozygous - 259T states. Delayed postnatal appearance of hepatic glucose-6-phosphatase in infants makes them vulnerable to hypoglycaemic episodes and this may occur in some SIDS infants. However, SIDS may be an association of more complex phenotypes in which several genes interact with multiple environmental factors. A UK-wide DNA Biobank of samples from all infant deaths, with an accompanying epidemiological database, should be established by pathologists to allow cumulative data to be collected from multiple genetic investigations on the same large cohort of samples, with the aim of selection of the best combination of genetic markers to predict unexpected infant death. PMID- 17354260 TI - Strategic use of preparative chiral chromatography for the synthesis of a preclinical pharmaceutical candidate. AB - The modern use of preparative chromatography in pharmaceutical development is illustrated by the case of a recent preclinical candidate from these laboratories. The synthesis of the candidate employed a coupling of two enantiopure intermediates, each of which could be resolved using preparative chiral chromatography. SFC screening was employed to identify the enantioselective stationary phases, and semipreparative SFC methods derived from this screening were used to produce gram amounts of enantiopure intermediate for initial studies. However, initial larger scale resolution required the translation of the SFC methods to HPLC conditions. Preparative chiral HPLC on a 30-cm i.d. column was then used to produce enantiopure intermediates which were coupled to give 170 g of the preclinical candidate. Subsequent preparation of the candidate at larger scale for later-stage clinical evaluation employed an improved synthesis in which one component was constructed by asymmetric synthesis. Resolution of the other component, now a more advanced intermediate, was carried out using newly obtained large-scale SFC equipment. Some discussion is presented on the varying strategies whereby preparative chiral chromatography can be used to support either short-term or long-term synthetic goals in preclinical pharmaceutical development. PMID- 17354261 TI - New route to enantiopure MalphaNP acid, a powerful resolution and chiral 1H NMR anisotropy reagent. AB - MalphaNP acid (+/-)-1, 2-methoxy-2-(1-naphthyl)propionic acid, was enantioresolved by the use of phenylalaninol (S)-(-)-4; a diastereomeric mixture of amides formed from acid (+/-)-1 and amine (S)-(-)-4 was easily separated by fractional recrystallization and/or HPLC on silica gel, yielding amides (R;S)-(-) 5a and (S;S)-(+)-5b. Their absolute configurations were determined by X-ray crystallography by reference to the S configuration of the phenylalaninol moiety. Amide (R;S)-(-)-5a was converted to oxazoline (R;S)-(+)-8a, from which enantiopure MalphaNP acid (R)-(-)-1 was recovered. In a similar way, enantiopure MalphaNP acid (S)-(+)-1 was obtained from amide (S;S)-(+)-5b. These reactions provide a new route for the large-scale preparation of enantiopure MalphaNP acid, a powerful chiral reagent for the enantioresolution of alcohols and simultaneous determination of their absolute configurations by (1)H NMR anisotropy. PMID- 17354262 TI - Easily recyclable chiral polymeric Mn(III) salen complexes for oxidative kinetic resolution of racemic secondary alcohols. AB - Chiral polymeric Mn(III) salen complexes were used efficiently for oxidative kinetic resolution of racemic secondary alcohols at room temperature. High chiral purity (ee; >99%) was achieved for the oxidative kinetic resolution of racemic secondary alcohols with 0.6 mol % catalyst loading in 60 min. The catalyst was easily recycled for five successive catalytic experiments. PMID- 17354263 TI - Homochiral oligopeptides via surface recognition and enantiomeric cross impediment in the polymerization of racemic phenylalanine N-carboxyanhydride crystals suspended in water. AB - As part of our program on the search of possible prebiotic routes for the formation of oligopeptides of homochiral sequence (isotactic) from racemic precursors in aqueous environment, we report the polymerization of racemic crystals of phenylalanine N-carboxyanhydrides, enantioselectively tagged with five deuterium atoms, suspended in water containing various amine initiators. Racemic mixtures of isotactic oligopeptides, comprising up to 25 repeat units of the same handedness, as the dominant component for each length, were observed in a MALDI-TOF mass spectrometry analysis. The racemic mixtures of the peptides could be desymmetrized by initiating the polymerization reaction with water soluble methyl esters of either enantiopure alpha-amino acids or dipeptides. A three-step mechanism is proposed to account for these results: (i) Surface recognition of the chiral initiator by the chiral sites present at specific faces of the crystal; (ii) Oligopeptide elongation at the polymer/crystal interface; and (iii) Self-assembly of the short isotactic peptides into racemic antiparallel beta-sheets as templates followed by cross-enantiomeric impediment in the growth of enantiomeric chains at the peptide beta-sheet/crystal interface. PMID- 17354264 TI - Comparative HPLC enantioseparation of ferrocenylalcohols on two cellulose-based chiral stationary phases. AB - The direct HPLC enantiomeric separation of several ferrocenylalcohols on the commercially available Chiralcel OD and Chiralcel OJ columns has been evaluated in normal-phase mode. Almost all the compounds were resolved on one or both chiral stationary phases (CSPs) with separation factor (alpha) ranging from 1.06 to 2.88 while the resolution (R(s)) varied from 0.63 to 12.70 In the separation of the alpha-ferrocenylalcohols 1a-e and the phenyl analogues 2a-e, which were all resolved except 1c, a similar trend in the retention behavior for the two series of alcohols was evidenced and the selectivity was roughly complementary on the two investigated CSP. For three ferrocenylacohols, chosen as model compounds, the influence of the mobile phase composition and temperature on the enantioseparation were investigated and additional information on the chiral recognition mechanism were deduced from the chromatographic behavior of their acetylderivatives. PMID- 17354265 TI - Chiral crystallization of glutamic acid on self assembled films of cysteine. AB - In this article, we describe the preparation and use of chiral surfaces derived from enantiomerically pure crystals of amino acids. For this purpose, we chose to employ a self-assembly process to grow nanoscale chiral films of (+)-L or (-)-D cysteine, onto gold surfaces. We utilized those chiral films as resolving auxiliaries in the crystallization of enantiomers from solutions. To demonstrate the chiral discriminating ability of the chiral surfaces in crystallization processes, we investigated the crystallization of rac-glutamic acid onto the chiral films. Our study demonstrates the potential application of chiral films to control chirality throughout crystallization, where one enantiomer crystallizes on the chiral surfaces with relatively high enantiomeric excess. In addition, crystallization of pure glutamic acid enantiomers, and its racemic compound on to chiral films resulted in crystal morphology modification with preferred crystal orientation, which assists in the interpretation of the ability of our chiral surfaces to function as chiral selectors. PMID- 17354266 TI - Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locus. AB - Anhidrotic ectodermal dysplasia (EDA) is a disorder of ectodermal differentiation characterized by sparse hair, abnormal or missing teeth, and inability to sweat. X-linked EDA is the most common form, caused by mutations in the EDA gene, which encodes ectodysplasin, a member of the tumor necrosis factor (TNF) family. Autosomal dominant and recessive forms of EDA have been also described and are accounted for by two genes. Mutations in EDAR, encoding a TNF receptor (EDAR) cause both dominant and recessive forms. In addition, mutations in a recently identified gene, EDARADD, encoding EDAR-associated death domain (EDARADD) have been shown to cause autosomal recessive EDA. Here, we report a large Moroccan family with an autosomal dominant EDA. We mapped the disease gene to chromosome 1q42.2-q43, and identified a novel missense mutation in the EDARADD gene (c.335T>G, p.Leu112Arg). Thus, the EDARADD gene accounts for both recessive and dominant EDA. EDAR is activated by its ligand, ectodysplasin, and uses EDARADD to build an intracellular complex and activate nuclear factor kappa B (NF-kB). We compared the functional consequences of the dominant (p.Leu112Arg) and recessive mutation (p.Glu142Lys), which both occurred in the death domain (DD) of EDARADD. We demonstrated that the p.Leu112Arg mutation completely abrogated NF-kB activation, whereas the p.Glu142Lys retained the ability to significantly activate the NF-kB pathway. The p.Leu112Arg mutation is probably a dominant negative form as its cotransfection impaired the wild-type EDARADD's ability to activate NF-kB. Our results confirm that NF-kB activation is impaired in EDA and support the role of EDARADD DD as a downstream effector of EDAR signaling. PMID- 17354267 TI - Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. AB - The catecholamine norepinephrine is a critical effector of the mammalian stress response and has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD)-a syndrome intrinsically related to the experience of extraordinary stress. Symptom-linked hypernoradrenergic derangements have been observed in PTSD and several studies have examined the potential therapeutic effects of agents that dampen the centrally hyperactive noradrenergic state. These agents include compounds that decrease norepinephrine release (e.g. centrally acting alpha(2) agonists such as clonidine) and those which block post synaptic norepinephrine receptors (e.g. centrally acting alpha(1) or beta receptor antagonists such as prazosin or propranolol). In this article, we review studies of central noreadrenergic hyperactivity under both basal and challenge conditions and explore the evidence for these derangements as potential psychopharmacologic targets in patients with PTSD. Given the significant involvement of CNS norepinephrine hyperactivity in PTSD, and its link to intrusive and hyperarousal symptoms, it is not surprising that interventions directed at this system have therapeutic potential in PTSD. The utility of these anti-adrenergics in the clinical treatment of PTSD remains to be determined, though it is possible that they may prove to have primary roles in a disorder that is only modestly responsive to antidepressant treatment. PMID- 17354268 TI - Does the evocation of traumatic memories confound subsequent working memory performance in posttraumatic stress disorder (PTSD)? AB - The role of heightened arousal has been previously discussed as a contributor to neurocognitive impairment in posttraumatic stress disorder (PTSD). To investigate whether psychological effects (distraction, re-location of resources) elicited by the evocation of traumatic memories impact on subsequent cognitive performance in PTSD, two parallel versions of a working memory task were administered to 33 trauma-exposed participants (15 with and 18 without PTSD). Between first and second working memory assessment a trauma-related interview was conducted including the narration of the trauma. Levels of working memory impairment in PTSD patients remained unchanged. This study provides preliminary evidence that neurocognitive impairment is not secondary to psychological effects induced by the evocation of traumatic memories. Nevertheless, it is recommended that future PTSD research should devote more care to the order in which trauma-related and other dependent variables such as cognitive tests are presented to participants. PMID- 17354270 TI - Current awareness on yeast. PMID- 17354271 TI - Estrogens and Human Diseases. Proceedings of a meeting, May 15-21, 2006, Erice, Italy. PMID- 17354272 TI - Determination of microcystins in environmental samples using capillary electrophoresis. AB - The applicability of capillary zone electrophoreses (CZE) and micellar electrokinetic chromatography (MEKC) methods for the simultaneous determination of two frequently occurring microcystins (MCs-LR and -YR) and a new variant (MC YA) in crude extracts of Hungarian bloom samples and cyanobacterial cultures was studied. It was found that the comparison of the results obtained by both CZE and MEKC measurements (due to the differences in their separation mechanisms) for the same sample can guarantee the reliability of the quantitative results. In our work environmental samples like lake waters, water bloom samples, cyanobacterial isolates were analysed. The three microcystins could be directly determined in water bloom samples collected from Hungarian lakes and laboratory culture samples of cyanobacteria. PMID- 17354273 TI - Abstracts from the meeting of the Nutrition Society of Australia and the Nutrition Society of New Zealand and IUNS & APCNS International Congress of Clinical Nutrition, 11-13 August 2004, Brisbane, Queensland. PMID- 17354274 TI - Determination of amino acids in saliva using capillary electrophoresis with fluorimetric detection. AB - In the present study a sensitive method for the quantification of main free amino acids in saliva using capillary electrophoresis with laser induced fluorescence detection was developed. As background electrolyte 20 mM borate buffer pH 9.5 was used. Amino acids were separated after derivatization were optimized. The main amino acids occurring in saliva (Pro, Ser, Gly and Glu) were separated in less than 7 min. The parameters of validation such as linearity of response, precision and detection limits were determined. The detection limits were obtained in the range from 0.1 to 2.4 nM. The developed method was employed for determination of amino acids in real saliva samples. PMID- 17354275 TI - Elementary school nurses' perceptions of student bullying. PMID- 17354276 TI - [Abstracts of the Epidemiology Congress, Dijon, France, 2006]. PMID- 17354277 TI - Recent progress in PYY research--an update report for 8th NPY meeting. AB - PYY(3-36) is a gut regulatory peptide which has recently been found to reduce appetite. Variability of this effect across different experimental conditions has led to confusion and polarization of opinion on its potential as an anti-obesity treatment. This review summarizes recent progress in this area. The basic anorexigenic effect leading to weight loss in rodents has now been confirmed by several groups. Anorexia has also been confirmed in human studies although optimal route and dosing remain to be defined. Gastric bypass causes PYY levels to rise, which may in part mediate the weight loss occurring after this surgery, and levels have been found to be normal or low in obese people. The straightforward ARC model of mechanism, involving inhibition and activation, respectively, of NPY and POMC neurons, is giving way to a more complicated system involving vagal afferent signals. CONCLUSION: It works, but not how we thought it did. PMID- 17354278 TI - Treatment default among new smear-positive pulmonary TB patients in Russian regions. PMID- 17354279 TI - Estimating glomerular filtration rate from serum creatinine in the general population. PMID- 17354280 TI - First generic metronidazole vaginal gel. PMID- 17354281 TI - Expanded use of Aricept. PMID- 17354282 TI - Partnership on cardiac safety. PMID- 17354283 TI - New recommendations to modernize drug manufacturing. PMID- 17354284 TI - The FDA approves drugs for colorectal cancer, lung cancer. PMID- 17354285 TI - New allergy treatment. PMID- 17354286 TI - A two-stage approach to the correction of ascertainment bias in complex genetic studies involving variance components. AB - Correction for ascertainment bias is a vital part of the analysis of genetic epidemiology studies that needs to be undertaken whenever subjects are not recruited at random. Adjustment often requires extensive numerical integration, which can be very slow or even computationally infeasible, especially if the model includes many fixed and random effects. In this paper we propose a two stage method for ascertainment bias correction. In the first stage we estimate parameters that pertain to the ascertained population, that is the population that would be selected into the sample if the ascertainment criterion were applied to everyone. In the second stage we convert the estimates for the ascertained population into general population parameter estimates. We illustrate the method with simulations based on a simple model and then describe how the method can be used with complex models. The two-stage approach avoids some of the integration required in direct adjustment, hence speeding up the process of model fitting. PMID- 17354287 TI - Development and function of secondary and tertiary lymphoid tissues. PMID- 17354288 TI - Th1/Th2 cross-regulation and the discovery of IL-10. AB - In the late 1980s, Tim Mosmann and colleagues isolated functionally distinct T helper (Th)-1 and Th2 clones, and provided evidence that these two subsets were mutually inhibitory. Knowledge of the inhibition led to the discovery that Th2 cells make IL-10 to suppress Th1 cells. PMID- 17354289 TI - Reality of rapid convergence. AB - A major series of conferences, workshops, and research projects has established the crucial importance of convergence across all fields of science and technology. Central to this unification at the present time are the NBIC fields: nanotechnology, biotechnology, information technology and new technologies based on cognitive science. This book provides an overview of this crucial phase change in human culture, beginning with four chapters offering an overview, followed by four chapters about nanobioconvergence, two about the ways in which information infrastructure can promote convergence, four chapters on cognitive technologies, and four addressing the social and ethical implications of this profound revolution. PMID- 17354290 TI - Help needed for pretransplant depression. PMID- 17354291 TI - C4d deposits as a possible marker for acute cellular liver rejection. PMID- 17354292 TI - Use of Aspergillus galactomannan enzyme-linked immunosorbent assay (ELISA) in liver transplant patients. PMID- 17354293 TI - Association of metabolic syndrome with white blood cell subtype and red blood cells. PMID- 17354294 TI - Humoral immune responses to the human immunodeficiency virus type-1 (HIV-1) in the genital tract compared to other mucosal sites. AB - Infection with the human immunodeficiency virus-1 (HIV-1) must be considered as a primarily mucosal disease. On a worldwide basis, the absolute majority of HIV infections occur through mucosal surfaces of the genital and intestinal tracts, and the earliest and most dramatic immunologic alterations are induced by the virus in mucosal tissues. However, individual compartments of mucosal components of the immune system display remarkable differences with respect to dominant antibody isotypes, virus phenotypes, densities and origins of cells involved in innate and specific immunity, presence or absence of inductive sites, and routes of immunizations that induce humoral and cellular responses. In this regard, the mucosal immune system of the female and male genital tracts exhibit several features which are distinct from other mucosal tissues, including dominance of the IgG isotype, local as well as pronounced systemic origin of antibodies, the absence of organized lymphoepithelial inductive sites and limited humoral responses stimulated by local antigen administration. Furthermore, it is evident that, irrespective of the route of infection, HIV-1 induces easily detectable IgG but not IgA specific antibody responses. These differences must be considered in the design of protective vaccines against infection with HIV and other agents of sexually transmitted diseases. PMID- 17354295 TI - Dose-intense chemotherapy in osteosarcoma. PMID- 17354296 TI - Genetic explanation for cisplatin-induced ear damage. PMID- 17354297 TI - Validity of Chinese herbal medicine called into question. PMID- 17354299 TI - High-dose chemotherapy in poor-risk germ cell tumours. PMID- 17354298 TI - Pemetrexed improves survival in pancreatic cancer. PMID- 17354300 TI - Allograft treatment increases risk of second tumour. PMID- 17354301 TI - Genetic firestorms signal aggressive cancer. PMID- 17354302 TI - Pioglitazone in nonalcoholic steatohepatitis. PMID- 17354303 TI - Pioglitazone in nonalcoholic steatohepatitis. PMID- 17354304 TI - Small-cell lung cancer responds to amrubicin. PMID- 17354305 TI - New vaccine to fight colorectal cancer. PMID- 17354306 TI - Children who date early more likely to smoke. PMID- 17354307 TI - Bivalirudin in acute coronary syndromes. PMID- 17354308 TI - Treatment of restenosis with a paclitaxel-coated balloon catheter. PMID- 17354309 TI - Compulsory HPV vaccination. PMID- 17354310 TI - Framework 7: back on track. PMID- 17354311 TI - The future of EORTC. PMID- 17354313 TI - The price of compromise: the Massachusetts health care reform. PMID- 17354314 TI - Stem cells: biopsy on frozen embryos. PMID- 17354315 TI - Norwood sought patients' rights. Republican Congressman from Ga. dies at age 65. PMID- 17354316 TI - Efficiency counts. IHA adds measures to pay-for-performance formula. PMID- 17354317 TI - Rolling the real-estate dice. N.Y. hospital selling choice location post bankruptcy. PMID- 17354318 TI - Peripheral neuropathy: experimental findings, clinical approaches. PMID- 17354319 TI - Pricing continues to rise. CPI, PPI increases marked by uptick in supply costs. PMID- 17354320 TI - When leaders become ill. PMID- 17354321 TI - Lipid-lowering therapy--benefits and risks. PMID- 17354322 TI - Self-harm in the general hospital. PMID- 17354323 TI - Emerging concerns abour Iran's scientific and medical future. PMID- 17354324 TI - Nursing and healthcare in England: students' perspectives. PMID- 17354325 TI - In vitro gene transfer using cationic vectors, electroporation and their combination. AB - BACKGROUND: The aim of this study was to investigate the transfection efficiency of cationic vectors (polyethylenimine; PEI25K and lipofectamine), electroporation and their combination in the human cancer cell lines, Raji human lymphoma and KB human oral carcinoma. MATERIALS AND METHODS: Raji human lymphoma and KB human oral carcinoma cell lines were transfected with pcDNA3-CMV-Luc at various N/P ratios of cationic vectors and voltages of electroporation, as well as with a combination of the cationic vectors and electroporation. RESULTS: The major findings were: (a) cationic vectors or electroporation alone increased transfection efficiency; (b) cationic vectors inhibited the transfection efficiency by electroporation. CONCLUSION: Our results demonstrate that cationic vectors and electroporation are feasible and efficient in transfecting human cancer cell lines. However, a combination of cationic vectors and electroporation is ineffective. PMID- 17354327 TI - Abstracts of the Nutrition Society meetings of 28 June-1 July 2005, 16-17 November 2005, 14-16 June 2006, and 3-6 July 2006. United Kingdom and Republic of Ireland. PMID- 17354326 TI - Abstracts from the 32nd Annual Meeting of the American Society for Histocompatibility and Immunogenetics. October 16-20, 2006. San Diego, California, USA. PMID- 17354328 TI - Abstracts from the International Congress XX on Endovascular Interventions. February 11-15, 2007. PMID- 17354329 TI - Factsheet: pandemic influenza. PMID- 17354330 TI - Abstracts from the Annual Conference of the Swiss Respiratory Society. March 8-9, 2007. Lugano, Switzerland. PMID- 17354331 TI - Abstracts of the SOGC (Society of Obstetricians and Gynaecologists of Canada) 62nd Annual Clinical Meeting. June 22-27, 2007. Vancouver, British Columbia, Canada. PMID- 17354332 TI - Abstracts from Transporters 2006, a workshop. September 6-9, 2006. Parma, Italy. PMID- 17354333 TI - Medicine and the arts. Oncologist Lost by B. A. St. Andrews. Commentary. PMID- 17354334 TI - Pharmacogenomics: an assessment of market conditions and competition. PMID- 17354335 TI - [Retrospective and perspectives in HBV drug-resistant variations]. PMID- 17354336 TI - Medicine and the arts. All Things Wise and Wonderful [excerpt] by James Herriot. Commentary. PMID- 17354337 TI - Spatial distribution and the animal landscape. PMID- 17354338 TI - Medicine and the arts. Sonnet by Stanley Plumly. Commentary. PMID- 17354339 TI - Chikungunya disease outbreak, Reunion Island. PMID- 17354340 TI - Martha E. Rogers over the years. PMID- 17354341 TI - Jean Watson over the years. PMID- 17354342 TI - Assay to detect H5N1 oseltamivir resistance. PMID- 17354343 TI - Laboratory exposure to influenza A H2N2, Germany, 2004-2005. PMID- 17354344 TI - Methicillin-resistant Staphylococcus aureus in cat and owner. PMID- 17354345 TI - Community-associated methicillin-resistant Staphylococcus aureus, Colombia. PMID- 17354346 TI - Live nativity and brucellosis, Sicily. PMID- 17354347 TI - Theoretical questions and concerns: response from the Theory of Culture Care Diversity and Universality perspective. PMID- 17354348 TI - Theoretical questions and concerns: response from a Caring Science framework. PMID- 17354349 TI - Cardiac CT angiography. PMID- 17354350 TI - HIV/AIDS specialist. PMID- 17354351 TI - [TUVRP and HOLEP as effective as TURP]. PMID- 17354352 TI - Nursing practice: imaging the possibles. PMID- 17354353 TI - Imagining nursing practice: the Roy Adaptation Model in 2050. PMID- 17354354 TI - The rise and rise of green chemistry in China. Interview conducted by Nicola Nugent. PMID- 17354355 TI - [Non steroidal anti-inflammatory analgesics in pain treatment. Orientation for primary care use]. AB - The high use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the current practice at the primary care level, and their frequently inappropriate prescription, due to ignorance in pharmacological side effects could cause devastating consequences for the patient's health. It was considered necessary to make a review of the more recent evidence about the NSAIDs, with the intention that medical doctors can be updated on the use of these drugs. The literature review was performed at the Ovid-Medline, Cochrane, Synergy, Medic latina, Science direct, Ebsco-e-journal services. In this article there is an emphasis about NSAIDS adverse effects, and actions suggested during their use. PMID- 17354356 TI - "The concept of intentionality in human science nursing theories". PMID- 17354357 TI - The lips of the dead and the "kiss of life": the contemporary deathbed and the aesthetic of CPR. PMID- 17354358 TI - Bitches, mollies, and tommies: Byron, masculinity, and the history of sexualities. PMID- 17354359 TI - Tradition, modernity, and Italian babies. PMID- 17354360 TI - [Modern characters]. PMID- 17354361 TI - Temperature measurements below the earth's surface: a history of records. PMID- 17354362 TI - [The Bayes pendulum: chronicle of a statistical polemic]. PMID- 17354363 TI - Historical aspects on mystics and metaphysics of metals. PMID- 17354364 TI - [Abstracts of the 112th Congress of the French Society of Ophthalmology. 6-10 May 2006, Paris, France]. PMID- 17354365 TI - "Botanical autobiography and vegetable wonders": Richard Schomburgk's botanical reminiscences of British Guiana. PMID- 17354366 TI - Electronic medical records--federal standards needed. PMID- 17354367 TI - The Wellmark and University of Iowa partnership: an innovative model for collaboration between Blue Cross-Blue Shield plans and colleges. AB - Wellmark Blue Cross-Blue Shield and the University of Iowa College of Public Health share a strong commitment to improving the health of communities they serve in Iowa and South Dakota. Beginning in 2002, these organizations forged an innovative partnership through which they annually select several collaborative projects that are congruent with their respective missions and address clearly defined needs. The outcomes of their joint efforts toward the partnership's goals are formally assessed on an annual basis. This cooperative arrangement has proven to be workable and beneficial, and may have applications in other settings. PMID- 17354368 TI - How do households choose their employer-based health insurance? AB - Using the 1996 Medical Expenditure Panel Survey, this study estimates a model of household demand for employer-based health insurance to investigate the set of plan and household characteristics that influence coverage choices. Overall, we find that households are sensitive to price with respect to their coverage decisions, and that price sensitivity varies by marital status, wealth, and the number of offers of employer coverage available to the household. We also find that lower-income households are less likely to select an option that provides coverage for all household members. Using our model estimates, we simulate the effect of employers offering various levels of "opt-out" payments on changes in workers' probabilities of not taking up coverage and on expected costs. PMID- 17354369 TI - Money and mandates: relative effects of key policy levers in expanding health insurance coverage to all Americans. AB - This study examines the relative effects of three policy levers on health coverage and costs in plans aimed at covering all Americans. Specifically, using microsimulation analysis and hypothetical proposals, it assesses how the generosity of financial assistance, an employer mandate, and an individual mandate affect the level of uninsurance, distribution of coverage, and federal costs, holding delivery system and benefits constant. The results suggest that only an individual mandate would cover all the uninsured; neither an employer mandate nor generous subsidies alone would be sufficient. The distribution of coverage would be least disrupted by an employer mandate, while 7.3% of people could lose employer coverage with generous subsidies and a voluntary purchasing pool. Federal costs would be highest under a combined individual and employer mandate since there would be costs to minimize disruption. Although less generous subsidies coupled with an individual mandate could yield universal coverage at a low federal cost, doing so would require large, new payments by individuals. Other key trade-offs are discussed. PMID- 17354370 TI - Effects of public premiums on children's health insurance coverage: evidence from 1999 to 2003. AB - This study uses 2000 to 2004 Current Population Survey data to examine the effects of public premiums on the insurance coverage of children whose family incomes are between 100% and 300% of the federal poverty level. The analysis employs multinomial logistic models that control for factors other than premium costs. While the magnitude of the estimated effects varies across models, the results consistently indicate that raising public premiums reduces enrollment in public programs, with some children who forgo public coverage having private coverage instead and others being uninsured. The results indicate that public premiums have larger effects when applied to lower-income families. PMID- 17354371 TI - Insurance premiums and insurance coverage of near-poor children. AB - States increasingly are using premiums for near-poor children in their public insurance programs (Medicaid/SCHIP) to limit private insurance crowd-out and constrain program costs. Using national data from four rounds of the Community Tracking Study Household Surveys spanning the seven years from 1996 to 2003, this study estimates a multinomial logistic regression model examining how public and private insurance premiums affect insurance coverage outcomes (Medicaid/SCHIP coverage, private coverage, and no coverage). Higher public premiums are significantly associated with a lower probability of public coverage and higher probabilities of private coverage and uninsurance; higher private premiums are significantly related to a lower probability of private coverage and higher probabilities of public coverage and uninsurance. The results imply that uninsurance rates will rise if both public and private premiums increase, and suggest that states that impose or increase public insurance premiums for near poor children will succeed in discouraging crowd-out of private insurance, but at the expense of higher rates of uninsurance. Sustained increases in private insurance premiums will continue to create enrollment pressures on state insurance programs for children. PMID- 17354372 TI - Effects of premium increases on enrollment in SCHIP: findings from three states. AB - This study examines the effects of new and higher premiums on SCHIP enrollment in Kansas, Kentucky, and New Hampshire--three states that implemented premium changes in 2003. We used state administrative enrollment records from 2001 to 2004-2005 to track changes in total caseloads, new enrollments, and disenrollment timing in premium-paying categories of SCHIP before and after the premium changes were implemented. Premium hikes were associated with lower caseloads in all three states and with earlier disenrollment in Kentucky and New Hampshire. Premium increases appeared to have greater disenrollment effects for lower-income children in New Hampshire and for nonwhite children in Kentucky. PMID- 17354373 TI - Access to health insurance, barriers to care, and service use among adults with disabilities. AB - No studies to date have examined access to insurance coverage or medical care for a broadly defined population of uninsured nonelderly adults with disabilities. This analysis uses the 2002 National Survey of America's Families to examine access to coverage, access to care, and service use for a large sample of adults with disabilities, with a focus on the uninsured. All disabled groups reported unmet need and service use greater than their nondisabled counterparts with the same insured status. Access to coverage was most problematic for low-income adults with work limitations but no other indication of disability, with over one third uninsured. This group deserves greater policy attention. PMID- 17354374 TI - [Advances in neuroscience and therapeutic research on neurological diseases--the present status and future prospects (discussion)]. PMID- 17354375 TI - [Neuropsychological approach to visual attention]. AB - Visual experience depends critically on visual attention, which selects a particular aspect of a visual display. Recent clinical, neuroimaging, and animal studies revealed that visual attention was divided into active and passive or top down and bottom-up attention. Although these dichotomies are clear-cut in definition, visual attention could be modulated by many factors. Detailed observation of brain-injured patients provides with evidence for dynamic and fine control of visual attention. We observed patients with dorsal simultanagnosia and that with callosal disconnection syndrome. Patients with dorsal simultanagnosia demonstrated that extent of visual attention was dynamically changed depending on the level of visual processing. Despite the ability to read a kanji character and to describe its components correctly, a patient could not notice a component that he had just written and could not assemble individual components to make up a correct kanji character. He could point to an overlapping area of two figures. But once he started to color the overlapping area, he missed the margin of the area and colored much larger area. Another patient with dorsal simultanagnosia missed borderlines between columns of a newspaper and read letters continuously across columns. In contrast, he could point to lines between figures or meaningless patterns easily. These findings indicated that visual attention was directed automatically to meaningful characters. A patients with callosal disconnection syndrome demonstrated left unilateral spatial neglect only when he used his right hand to draw figures. Right hand movement, controlled by the left hemisphere, elicited visual attention to the right hemispace, resulting in the left unilateral spatial neglect. Thus visual attention is not simply top-down or bottom up, but is implicitly affected by the visual recognition as well as motor component of the task. PMID- 17354376 TI - [Neural mechanisms for object and color recognition]. AB - We reported double-dissociation between the visual processing of the edges and the surfaces of objects. Patients with lateral occipital damage showed selective impairment in the perception of edges whereas those with medial ventral occipital damage showed selective impairment in the perception of the 3D structure of the surface. Patients with medial ventral occipital damage also exhibited impaired perception of color, which is also a surface property. Those results were consistent with those from neuroimaging studies. Taken together, those studies suggest that objects may be processed in two separate pathways in the ventral occipital cortex: the edges of objects are processed in the lateral pathway and the surface of objects are processed in the medial pathway. Both edges and surfaces play important roles in object recognition, and both types of perception should be evaluated in patients with visual agnosia. PMID- 17354377 TI - [Parallel processing of motion vision]. AB - Several neuropsychological studies have reported dissociation between motion vision and object vision. One patient with motion blindness had a bilateral MT/V5 lesion and could see objects, but could not see the motion of the objects (Zihl et al, 1983). By contrast, some blindsight patients with primary visual cortex lesions cannot see objects but can see their movement (e.g. Riddoch, 1917). These results imply that movement vision and form vision rely on independent mechanisms. However one patient with motion blindness had controversial symptoms concerning motion vision. She could not perceive the movement of objects, although she could walk without colliding with obstacles and could catch incoming objects. It has also been reported that patients with a bilateral parietal lesion had well-preserved primary motion vision, but had problems walking and catching a ball (Vaina, 1998). Therefore, motion for vision and motion for action might have independent mechanisms. Such dissociation has also been noted in patients with Balint syndrome. Some patients behave like a blind person but can walk and catch a ball, while other patients bump into obstacles while walking. These results indicate that the neural bases of motion vision are distinct from those of form vision and that there are subdivisions of motion vision. PMID- 17354378 TI - [Neural mechanisms of facial recognition]. AB - We review recent researches in neural mechanisms of facial recognition in the light of three aspects: facial discrimination and identification, recognition of facial expressions, and face perception in itself. First, it has been demonstrated that the fusiform gyrus has a main role of facial discrimination and identification. However, whether the FFA (fusiform face area) is really a special area for facial processing or not is controversial; some researchers insist that the FFA is related to 'becoming an expert' for some kinds of visual objects, including faces. Neural mechanisms of prosopagnosia would be deeply concerned to this issue. Second, the amygdala seems to be very concerned to recognition of facial expressions, especially fear. The amygdala, connected with the superior temporal sulcus and the orbitofrontal cortex, appears to operate the cortical function. The amygdala and the superior temporal sulcus are related to gaze recognition, which explains why a patient with bilateral amygdala damage could not recognize only a fear expression; the information from eyes is necessary for fear recognition. Finally, even a newborn infant can recognize a face as a face, which is congruent with the innate hypothesis of facial recognition. Some researchers speculate that the neural basis of such face perception is the subcortical network, comprised of the amygdala, the superior colliculus, and the pulvinar. This network would relate to covert recognition that prosopagnosic patients have. PMID- 17354379 TI - [Prevention of brain infarction in patients with atrial fibrillation]. AB - The patients with cardioembolic stroke sometimes suffer from severe neurological deficit and from recurrent strokes. Since atrial fibrillation, especially non valvular atrial fibrillation (NVAF) is associated with over half of the cardioembolic strokes, the prevention of cardioembolic stroke in patients with NVAF is important. There have been some reports about how to prevent stroke. They have indicated that the best medication for preventing from stroke was anticoagulation by warfarin. Therefore, the guidelines recommended the patients with NVAF to take warfarin. In case with the older patients under 70 years, prothrombin international normalized ratio (PT-INR) should be kept from 2.0 to 3.0. On the other hand, if the patients with NVAF are over 70 years, PT-INR has to be controlled from 1.6 to 2.6. Before extraction of a tooth, anticoagulation should not be call off. PMID- 17354380 TI - [Adult-onset citrullinemia]. AB - Adult-onset citrullinemia (CTLN2) is a rare hereditary metabolic disorder characterized by highly increased concentration of citrulline and ammonia in the plasma, which is ascribed to a deficiency of argininosuccinate synthetase (ASS), one of the urea cycle enzymes mainly located in the liver. Neurological manifestation in CTLN2 patients closely resemble those of hepatic encephalopathy and in the past, most patients usually followed rapidly deteriorating clinical courses and died of severe brain edema within a few years after onset. However, in 1995 the first CTLN2 patient who was successfully treated by living-related liver transplantation was reported and since then more than 30 patients had underwent this operation in our country, showing good outcomes. No primary defect had not been found within ASS gene locus, but the causative gene of this disorder is now identified as the "citrin gene", which might act as a aspartate/glutamate transporter in mitochondria. Different phenotypes are seen in the individuals with a citrin deficiency: neonatal intrahepatic cholestasis, juvenile-onset chronic pancreatitis and hepatocellular carcinoma without cirrhosis can precede the appearance of CTLN2. The precise pathogenesis of this disease that includes the relationship between the mutations of citrin gene and a deficiency of hepatic ASS activity remains unclear. PMID- 17354381 TI - [Development of the Telephone Interview for Cognitive Status (TICS) in Japanese]. AB - In recent years, population of elder people has increased in Japan, following augmentation of the number of people with dementia in Japan. Then it is important to detect cognitive impairment in early stage for adequate treatment, care and prevention. We studied 135 subjects, 49 patients with Alzheimer's disease (AD) and 86 healthy controls using Telephone Interview for Cognitive Status (TICS), and developing Japanese version of the TICS (TICS-J). The sensitivity and the specificity of the TICS-J to differentiate AD patients from healthy controls was 98.0% and 90.7%, respectively. Pearson's correlation coefficiency between the TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p < 0.001). On the receiver operating curves, the area under the curve for the TICS-J was 98.7% (95% CI: 97.5%-100%). These results indicate that TICS-J is sensitive and specific instrument for differentiating AD patients from healthy controls. PMID- 17354382 TI - [Case of ruptured superior cerebellar artery dissection treated by endovascular embolization]. AB - The authors herein report a case of a ruptured dissection of the superior cerebellar artery (SCA). A 68-year-old man presented with symptons of sudden headache and nausea. The CT scan revealed the presence of both a subarachnoid hemorrhage (SAH) and acute hydrocephalus. The left vertebral angiogram showed an fusiform dilatation in the cerebellomesencephalic segment of the left SCA. Endovascular embolization of the aneurysm and SCA was successfully performed using Guglielmi detachable coils (GDCs). No delayed ischemic deficits were observed after the treatment. A dissection of the distal segment of the SCA is a very rare occurrence. We believe endovascular embolization using GDCs to be an effective and less invasive therapy for the treatment of an SCA dissection with SAH. PMID- 17354383 TI - [Autopsied case of 89-year-old female complicated with dementia after 14 years from the onset of spastic gait, in her total 27 years of clinical course]. PMID- 17354384 TI - Checklist of the helminth parasites of vertebrates in Costa Rica. AB - Helminth parasites of vertebrates have been studied in Costa Rica for more than 50 years. Survey work on this group of parasites is far from complete. We assembled a database with all the records of helminth parasites of wild and domestic vertebrates in Costa Rica. Information was obtained from different sources such as literature search (all published accounts) and parasite collections. Here we present a checklist with a parasite-host list as well as a host-parasite list. Up to now, 303 species have been recorded, including 81 species of digeneans, 23 monogeneans, 63 cestodes, 12 acanthocephalans, and 124 nematodes. In total, 108 species of vertebrates have been studied for helminths in Costa Rica (31 species of fishes, 7 amphibians, 14 reptiles, 20 birds, and 36 mammals). This represents only 3.8% of the vertebrate fauna of Costa Rica since about 2,855 species of vertebrates occur in the country. Interestingly, 58 species (19.1 %) were recorded as new species from Costa Rica and most of them are endemic to particular regions. Considering the valuable information that parasites provide because it is synergistic with all the information about the natural history of the hosts, helminth parasites of vertebrates in Costa Rica should be considered within any initiatives to accomplish the national inventory of biological resources. Starting with this compilation work, the Coleccion de Helmintos de Costa Rica (CHCR), hosted at the Facultad de Microbiologia, Universidad de Costa Rica, has re-emerged and it is our hope that it will have the standards of quality to assure that it will become the national depository of helminths in the country. PMID- 17354385 TI - Addendum to the checklist of the helminth parasites of vertebrates in Costa Rica. AB - In this work, we present an addendum to the "Checklist of the helminth parasites of vertebrates in Costa Rica" with a parasite-host list as well as a host parasite list. This addendum updates the available information on this group of parasites in Costa Rica, since very recently a new input has been made to describe the helminth fauna of vertebrates, particularly at the Area de Conservacion de Guanacaste. In this paper, we add 33 records, representing 23 species. This raises the number of helminth species described in vertebrates from Costa Rica to 325, represented by 89 species of digeneans, 23 of monogeneans. 63 of cestodes, 13 of acanthocephalans, and 137 of nematodes. In total, 133 species of vertebrates have been studied for helminths in Costa Rica (31 species of fishes. 7 amphibians, 18 reptiles, 40 birds, and 37 mammals). Currently, 67 species (20.6 %) have been recorded as new species from Costa Rica and most of them are endemic to particular regions. The Colecci6n de Helmintos de Costa Rica, housed at the Universidad de Costa Rica (UCR), San Jose, is the depositary of only 23% of the species recorded so far; however this situation is changing and people recognizes. PMID- 17354386 TI - A new species of Microphallus (Trematoda: Microphallidae) from Venezuela. AB - During 1997-1999, a total of 94 crabs, Uca rapax were collected from La Sabana, La Ceiba and El Paujil, Sucre State, Venezuela. Of these 36 were infected with metacercariae. Two parasites were located in the abdominal muscles and one under the tissue of carapace and gonad. These metacercariae grew to adults in the following genera: Levinseniella, Microphallus and Maritrema, in the period of 2-5 days after feeding experimentally to the rat Rattus norvegicus, mice Mus musculus and duck Cairinia moschata. Specimens of the genus Microphallus were described herein as a new species M. sabanensis. The life cycle of M. sabanensis sp.nov. were studied experimentally using rat, mice and duck. All developmental stages and the adult are described. In addition, M. sabanensis was collected from wild birds Anas discors, Pluvialis squatarola, Butorides striatus, Egretta caerulea and Nycticorax violaceus from the same localities. PMID- 17354387 TI - [Gnathostoma binucleatum (Spirurida: Gnathostomatidae) from the freshwater fish in Tabasco, Mexico]. AB - Human gnathostomiasis is a food-born parasitic disease of relative importance in many countries in Southeast Asia. It is caused by several species of nematodes of the genus Gnathostoma. In Mexico is an emerging public health problem since 1970, when first cases were reported. Until today, larval morphometric characters that have been proposed to differentiate between the three species of Gnathostoma present in this country, are not satisfactory. Recently, the presence of advanced third-stage larvae AdvL3 (infective form for humans) in freshwater fishes from Pantanos de Centla, Tabasco. was recorded but their specific identity was not clarified . Examination of four species of freshwater fishes from the same locality revealed that three of them: Petenia splendida (n=58), Cichlasoma managuense (n=35) and Gobiomorus dormitor (n=9) were infected by 15 AdvL3 of Gnathostoma binucleatum. Specific identity was obtained comparing the internal transcribed spacer 2 (ITS2) of the ribosomal DNA with sequences reported in Genbank. This is the first record of G. binucleatum in P. splendida and G. dormitor from Tabasco and the first specific determination of the parasite in the locality. PMID- 17354388 TI - [Morphology of some tricostrongilinae (Strongylida) from the National Helminth Collection, Institute of Biology, UNAM, Mexico]. AB - The present study analyses the taxonomic status of eleven species of trichostrongylins that parasitize rodents and lagomorphs deposited in the Coleccion Nacional de Helmintos, Instituto de Biologia. UNAM. Mexico. This analysis is based on the morphology of the synlophe, characteristic that had not been studied for most of these nematode species and at present, it has a very important taxonomic value. As a result of this study, the identity of five species is ratified (Trichostrongylus calcaratus, Obeliscoides cuniculi, Carolinensis huehuetlana. Stilestrongylus peromysci and Nippostrongylus brasiliensis), the transference suggested previously for two more (Vexillata convoluta and Vexillata vexillata) is confirmed, Trichostrongylus chiapensis is synonymized with Boehmiella willsoni, and finally Lamothiella romerolagi is re determined as Teporingonema cerropeladoensis and Stilestrongylus atlatilpinensis as Stilestrongylus hidalguensis. PMID- 17354389 TI - Gastrointestinal helminth parasitism in fruit-eating bats (Chiroptera, Stenodermatinae) from western Amazonian Brazil. AB - In this paper we report endoparasites from a sample of 50 stenodermatine bats collected mainly over lick sites at the Parque Nacional da Serra do Divisor, westernmost extremity of Amazonian Brazil. Four helminth species were recovered (Hasstilesia tricolor, Vampirolepis elongatus, Cheiropteronema globocephala. and Capillaria sp.), most of them from small intestines. Overall helminth prevalence achieved 26% (13/50) and the more prevalent species was H. tricolor (20%). Previously unknown in bats and reported for the first time in Brazil, this digenetic trematode was found in seven of the 18 bat species studied here. We argue that the drinking behaviour of stenodermatines at lick sites may be implicated in the dissemination of helminth infection among these bats. PMID- 17354390 TI - [Helminths from the fish Dormitator maculatus (Osteichthyes: Eleotridae) from Alvarado, Veracruz, Mexico]. AB - Dormirator maculatus (n=184) was collected in the Alvarado Lagoon, Mexico during a year period (Oct. 1993-1994). In the helminthologic review, the presence of Clinostomum complanatum (82.3%), Neoechinorhynchus golvani (76.1%), Spiroxys sp. (21.3 %), and Camallanus sp. (6.2%) was registered. Reduction of the hematocrit caused by such infection is significant (t, a= 0.05). PMID- 17354391 TI - [Macrophytes from some high Andean lakes of Ecuador and their low potential as bioindicators of eutrophication]. AB - The occurrence of macrophyte in three high Andean lakes of Ecuador, Lago San Pablo, Laguna La Mica and Lago Cuicocha was recorded in 5-9 transects per lake. The first two lakes are eutrophic, the third is an extremely oligotrophic caldera lake. The dominant species in eutrophic lakes are Ceratophyllum demersum, Myriophyllum quitense, Polamogeton illinoensis, P. striatus and Elodea matthewsii. In the oligotrophic lake P. pectinatus, P. illinoensis, and the Characeae Chara rusbyana, Ch. globularis and Nitella acuminata occur. The maximum depth of the macrophyte's presence can be used as an indicator of the trophic state, ranging from about 5 m in Mica to 35 m in Cuicocha. The bioindication value of the macrophyte species in these high Andean lakes is low, because few species occur and because some of them are not specific to environmental conditions. PMID- 17354392 TI - Photochemical efficiency of adult and young leaves of the neotropical understory shrub Psychotria limonensis (Rubiaceae) in response to changes in the light environment. AB - We explored the short-term adjustment in photochemical efficiency (Fv/Fm) in adult and young leaves of the understory neotropical shrub Psychotria limonensis Krause (Rubiaceae) in response to rapid changes in the light environment. Leaves were collected from 20 individual plants growing under sun and shade conditions on Gigante Peninsula, Barro Colorado Natural Monument (Republic of Panama), during the wet season of 1996. Leaves were distributed in four sequences of light treatments (AB leaves were expanded under sun and were transferred to shade, BA leaves experienced the opposite transfer, and the controls AA and BB leaves that were expanded and maintained under sun or shade conditions). Adult and young leaves did not differ in overall photochemical efficiency. Instead, differences were found among light environments, for which leaves transferred from shade to sun showed the lowest Fv/Fm ratios. There was no relationship between photochemical efficiency and leaf temperature. In P. limonensis, understory plants are susceptible of photoinhibition independently of the leaf ontogenetic stage. The approach utilized in this experiment allowed the rapid exploration of this capacity, and could be applied to poorly studied understory species. PMID- 17354393 TI - Use and management of mimosa species in the Tehuacan-Cuicatlan Valley, a tropical semi-arid region in Mexico (Fabaceae-Mimosoideae). AB - We report on the use of 15 Mimosa species within the Tehucan-Cuicatlan Valley, south-central Mexico. Seven of these species are endemic to Mexico, and four species and one variety are endemic to the Valley. We reviewed historical, ethnobotanical and floristic manuscripts, and conducted field studies. Several herbaria were consulted, as well as the BADEPLAM data base. Field work in the Valley has been done from 1994 to date. Most of the Mimosa species occur in the arid tropical scrub and the tropical deciduous forest, which are considered the most endangered vegetation types of the Valley. Our findings show that Mimosa species are used as fodder (45%), fuel (31%), living fences (14%) and construction material (7%). Only one species is used as medicine. Mimosa species are "multipurpose" shrubs/trees of the agrosilvopastoral system of this region. PMID- 17354394 TI - A source of almost pure methyl chavicol: volatile oil from the aerial parts of Tagetes lucida (Asteraceae) cultivated in Costa Rica. AB - The plant Tagetes lucida Cav. (syn. T. florida Sweet, T. schiedeana Less.) is an aromatic herb distributed naturally from Mexico to Honduras, at elevations between 1 000 and 2 000 m. It is used as a spice, for medicine, as insecticide and as ornamental plant. It is cultivated commercially in Costa Rica as a spice herb; it contains an oil having an anise-like odor, and the fresh aerial parts of this plant are sold in the supermarket as a substitute of tarragon (Artemisia dracunculus L.). The essential oils isolated from aerial parts bought, at May and October, in a supermarket in San Jose (Costa Rica). Fresh flowering aerial parts, flowers and leaves plus stems, were subjected to hydrodistillation for 3 hr using a modified Clevenger-type apparatus. The distilled oils were collected and dried over anhydrous sodium sulphate and stored in a freezer (0-10 degrees C). The light yellow green oil yield was about 0.07% (v/w). GC/MS analyses were performed using a Shimadzu GCMS-QP5050 apparatus and CLASS 5000 software with Wiley 139 computer database. Identification of the components of the oil was performed using the retention indices, which were calculated in relation to a homologous series of hydrocarbons, and by comparison of their mass spectra with those published in the literature or those of our own database. Thirty compounds were identified, of which methyl chavicol (95-97%) was the major constituent. From flower oil, two bithienyls were detected as minor constituents. PMID- 17354395 TI - Sexual reproduction of the reef-building coral Diploria labyrinthiformis (Scleractinia: Faviidae), in the Colombian Caribbean. AB - Sexual reproduction of the coral Diploria labyrinthiformis was studied for the first time. Monthly histological analyses at the Corales del Rosario National Park (Colombian Caribbean) from May 1997 to April 1998 show that D. labyrinthiformis is a hermaphroditic broadcasting species. It presents an annual gametogenic cycle with a 10-11 month period for gonad investment, in which oogenesis begins in August and ends in May-June. Spermiogenesis is short because sperm cysts were only observed in May tissue samples. In histological collected in May, an average of four mature eggs and six spermatic cysts per fertile mesentery were found. The mean diameter of mature eggs was 297 microm (+/- 97 SD) and 90 microm (+/- 33) for spermatic cysts. Rapid maturation of eggs from stage II to stage III coincides with increases in air temperature, high number of solar hours per month, decreases in wind velocity and absence of rainfall. Reproductive effort for D. labyrinthiformis (14.07 mm3/cm2/year) was similar to other Faviidae species. Although gamete release was not observed in the field, the absence of gonads in histological samples in June suggests spawning between May 25 (five days after full moon) and June 24. This event coincides with high air temperature, low number of solar hours per month, low wind velocity, and initiation of the rainy season. The earlier spawning time of this species differs from other species of the same family known for the Caribbean region. PMID- 17354396 TI - Akumal's reefs: stony coral communities along the developing Mexican Caribbean coastline. AB - Fringing coral reefs along coastlines experiencing rapid development and human population growth have declined worldwide because of human activity and of natural causes. The "Mayan Riviera" in Quintana Roo, Mexico, attracts large numbers of tourists in part because it still retains some of the natural diversity and it is important to obtain baseline information to monitor changes over time in the area. In this paper, the condition of the stony corals in the developing coastline of the Akumal-area fore reefs is characterized at the start of the new millennium at two depths, and along an inferred sedimentation gradient. Transect surveys were conducted in five fringing reefs starting at haphazardly chosen points, with respect to species composition, live cover, colony density, relative exposure to TAS mats and, for one species (Diploria strigosa, Dana, 1848), tissue regression rates in the presence of TAS mats. Fish population density and herbivory rates are also assessed. Data from line intercept transects (n=74) show that live stony coral cover, density and relative peripheral exposure of colonies to turf algal/sediment (TAS) mats were inversely related to an inferred sediment stress gradient at 13m. In 2000, live stony coral cover had decreased by 40-50% at two sites studied in 1990 by Munoz-Chagin and de la Cruz-Aguero (1993). About half of this loss apparently occurred between 1998 and 2000 during an outbreak of white plague disease that mostly affected Montastraea faveolata, and M. annularis. At a 13 m site, where inferred sedimentation rates are relatively high, time series photography of tagged Diploria strigosa, (n=38) showed an average loss of 70 cm2 of live tissue/coral/year to encroachment by TAS mats during the same period. Whereas densities of carnivorous fishes and herbivores (echinoids, scarids, acanthurids and Microspathodon chrysurus) in 2000 were low in belt transects at 10-19 m (n=106), turf-algal gardening pomacentrids were relatively common on these reefs. PMID- 17354397 TI - [Live coral predation by fish in Tayrona Nature National Park, Colombian Caribbean]. AB - Live coral predation by fish was evaluated in two bays of the Tayrona National Natural Park (Colombia), as a possible biological agent causing coral mortality. Visual censuses were used to identify the most important predator. Predation incidence was determined by examining all colonies present in permanent belt transects (20 x 2 m) in two reef environments (one dominated by Colpophyllia natans and the other one by Montastraea faveolata), for two climatic seasons (rainy and dry seasons). The parrotfish Sparisoma viride was the most important predator due to its biting frequency and bite size. S. viride adults of the initial and terminal phases, removed live tissue and part of the calcareous matrix of M. faveolata, M. annularis, Porites astreoides and C. natans, of which, the last one lost a major amount of tissue per area (3.51 cm2) and volume (3.22 cm3) per bite. A negative exponential tendency (r2=0.94), between coral density and volume removed was found, indicating that the coral density determines the bite's damage. There is no clear relationship between predation incidence and climatic seasons at the sites studied. At Chengue and Gayraca bays, live coral predation is one of the factors contributing to coral tissue loss and could have important consequences on the dynamic of these reefs. PMID- 17354398 TI - Composition of the zooplankton community, with emphasis in copepods, in Punta Morales, Golfo De Nicoya, Costa Rica. AB - The composition of the mesozooplanktonic community was studied in the Punta Morales estuary, Gulf of Nicoya, Pacific coast of Costa Rica, during 1997. Oblique plankton hauls were performed during high and low tide using a 280 microm mesh screen net equipped with a flowmeter. The community was characterized by holoplanktonic and meroplanktonic organisms. For the holoplanktonic community, the main groups were copepods (80%) and chaetognaths (16%). The most abundant species were the copepods Acartia lilljeborgii and Paracalanus parvus. A. lilljeborgii is a typical estuarine species that maintains high populations in estuarine systems. Meroplankton was represented mainly by crustacean larvae (66%), and icthyoplankton (18%). The dominance of crustacean larvae and icthyoplankton is an evidence of the ecological importance of the Punta Morales zone. PMID- 17354399 TI - Embrionary and larval development of the marine clam Tivela mactroides (Bivalvia: Veneridae) in Zulia State, Venezuela. AB - The marine clam, Tivela mactroides, from Cano Sagua beach, Venezuela, was spawned and reared under laboratory conditions to monitor its early development. Spawning was spontaneous but in some cases it had to be induced by the additon of eggs and sperm. After fertilization, the embryonic development occurred at 5 hr approximately. Trochophore larvae were observed between eight and ten hours later. Straight-hinged veliger stage appeared 15 hr after fertilization. Transition from veliger stage to the umbo stage occurred about eight days after fertilization. Pediveliger stage was observed 22 days after fertilization. Metamorphosis of T. mactroides was not successful under our laboratory conditions; probably the bacterial contamination and subsequent mortalities were important factors constraining the final phase of the larval cycle. However, in a few cases young individuals were observed. We suspect that this was due to unfavorable conditions (e.g.: bacterial contamination, unsuitable food availability, etc.) and the broad variation in developmental times, suggesting that these stages might be particularly sensitive to environmental changes. These results may not necessarily reflect what happens under natural conditions. PMID- 17354400 TI - [Abundance of the sea urchin Centrostephanus coronatus (Echinoidea: Diadematidae) in the Costa Rican Pacific]. AB - Centrostephanus coronatus reaches a density of 0.06 individuals/m2 in shallow reef waters in Parque Nacional Marino Ballena, Pacific of Costa Rica, in the same habitat occupied by the urchin Diadema mexicanum. It is the fourth species of diadematoid urchins reported for Costa Rican and a first new report for Central America. PMID- 17354401 TI - [Dipteran parasitoidism on larvae of Caligo atreus (Lepidoptera: Nymphalidae) in Cartago, Costa Rica]. AB - Parasitoids on larvae of Caligo atreus were studied at the Estacion de Biologia Tropical in Rio Macho, Cartago, Costa Rica. (1 600 masl), from March through July 2000. Fifth instar larvae of C. atreus were placed on Heliconia tortuosa Griggs var. Red Twist (Heliconiaceae) host plants at a mean temperature of 16.7 degrees C. The parasitoids obtained belong to an unidentified species of the genus Winthemia (Diptera: Tachinidae). Most flies emerge some 40 days after the eggs were laid (maximum 68 days). They make an orifice on the upper ventral part of the lepidopteran pupa. Winthemia is used commercially as biological control of cotton and banana. PMID- 17354402 TI - The "windows", scales, and bristles of the tropical moth Rothschildia lebeau (Lepidoptera: Saturniidae). AB - The common Spanish name of the moth Rothschildia lebeau (Saturniidae) is cuatro ventanas (four 'windows'), because it exhibits a transparent oval path in each wing. The scales of the colored areas and the bristles from the "window" were analyzed. We developed a simple device to measure transmittance across the "windows" with an spectrophotometer. A square section of "window" was mounted onto a flat black card and placed onto a clamp that hung in the path of the light - beam of the spectrophotometer. Absorbance was measured at 350 and 550 nm, with the "window" positioned perpendicular to the light beam (incidence of 90 degrees); then the measurements were repeated with the "window" moved at an angle of 45 degrees. Each measurement was replicated 5 times. Wing color spots were analyzed with a light dissection microscope (stereoscope) and with scanning electron microscopy. The scales have a minimum of 4 morphological types, 3 of them showed the typical appearance of unspecialized scales described for other butterflies; whereas the fourth has features particular to this species. On the "window" the scales are transformed in hair-like bristles that do not interfere with light, conferring the transparency that characterizes the "windows". However, if the wing is illuminated at an almost grazing-incidence, they reflect the light as a mirror. Two hypothetical functional explanation for the windows are mimicry and interspecies communication. PMID- 17354403 TI - [Defecation index and reproductive success of Triatoma maculata (Hemiptera: Reduviidae) under laboratory conditions]. AB - The reproductive and defecating behavior of Triatoma maculata (Erichson 1848) was studied on animals from an university culture in Venezuela. This species does not reach the importance of Rhodnius prolixus Stal 1859 as Chagas disease vector in Venezuela. This study addressed the role of defecating frequency, an index of how dangerous the animals are for the human population, and its relationship with why T. maculata is a less important vector than R. prolixus. Human blood was fed to the insects through an artificial feeding device. The 2nd and 3rd instar nymphs defecated more frequently (Id= 0.6, n=40), and our Vth instar nymphs did not complete sexual differentiation. Fertility was 55% (n=865) and fecundity 8 eggs/female/week (n=26). Egg incubation lasted 22 days (n=477). Female longevity was 51 days (n=26). Intermould time grew progressively from 35 days for 1st to 40 days for 4th instar nymphs (n=40). Mould percentage varied from 0% for Vth to 63% for 3rd instar nymphs. Mortality varied from 8% for 3rd to 100% for Vth instar nymphs. These results support evidences explaining the lesser vectorial capacity and low density of T. maculata in human domiciles, including reduced reproduction and defecation when the animal feeds on human blood. PMID- 17354404 TI - A mass collection of Triatoma ryckmani (Hemiptera: Reduviidae) from Stenocereus Eichlamii (Cactaceae) in the semiarid region of Guatemala. AB - A population of 216 specimens of Stenocereus eichlamii (Cactaceae, Subfamily Cereoideae) was surveyed for Triatoma ryckmani (vector of Chagas disease) in a one hectare plot of semiarid habitat in Guatemala. Out of 44 plants that had dead and dry sections, 24 plants had a total of 103 specimens of T. ryckmani. In comparison with other areas of Guatemala, T ryckmani is well established in the semiarid ecosystem (Infestation index 54.5, density = 2.3 and crowding index 4.3). The insects were mainly found (52.4%) in the dead portions of S. eichlamii 2.0 to 3.2 m above the ground (X2 = 26.0, P < 0.00001), followed by dry cactus sections between 3.2 and 5.0 m (35.9%). They were less frequent 0.2 to 2.0 m above the ground. A considerable proportion (75.7%) had no aparent blood in their digestive systems. To determine the presence of flagellates, 43 of the bugs were dissected, but none were found. This is the first report on T. ryckmani population dynamics in this habitat. PMID- 17354405 TI - [Effect of the probiotic Bacillus subtilis on the growth and food utilization of tilapia (Oreochromis niloticus) and prawn (Macrobrachium rosenbergii) under laboratory conditions]. AB - Three experiments were conducted to analyze the effect of the probiotic Bacillus subtilis on the growth of juvenile tilapia (Oreochromis niloticus) and freshwater prawn (Macrobrachium rosenbergii). The experiments were conducted under laboratory conditions, minimizing the indirect effects of the probiotic on the water quality and leaving only the possible bactericidal and digestion-support effects. A model of stress was also designed in tilapia to compare the effect with tilapia under normal conditions. The dose in the food was 0.1% of the probiotic (5 x 10(8) CFU/g and 99.9 % maltrine) in the dry diet. Every 14 days the animals were weighed in group (tilapias +/- 0.1 g, prawns +/- 0.001 g) to estimate average body weight. In the first experiment (tilapia) the specific growth rate (SGR) and the feed conversion ratio (FCR) were bad in relation with the factor probiotic, but the differences were not significant. In the second experiment (tilapia) both the SGR and the FCR deteriorated with the addition of B. subtilis to the diet; the difference was significant to 94%. The stress factor, on the contrary, caused a notable worsening of both the growth and the food utilization. In the experiment with prawns the addition of B. subtilis caused a light deterioration of the growth and of the food utilization, with a statistical probability of mistake of 10% in case of the growth. During the experiment the direct effects over the digestive system should have prevailed, either by the contribution of macro- and micronutrients, or by the enzymes that contribute to the digestion. The negative effect due to the addition of the probiotic to the food was small (about 10% in both the SGR and the FCR) being difficult to detect statistically. The reports on the positive action of probiotics on the growth in aquatic animals have been conducted mainly in ponds, and our information does not contradict directly a possible positive action of B. subtilis in this type of systems. Since the effect on the digestive system seems to be relatively small, in those environments the effect might be compensated by other positive effects on water quality, and by bactericidal effects on pathogenic bacteria. PMID- 17354406 TI - [Fertility, fecundity and gonadosomatic index of Poecilia reticulata (Pisces: Poeciliidae) in Heredia, Costa Rica]. AB - Between September and November of 1998, 1 432 females of Poecilia reticulata were collected in a pond in Santo Domingo, Heredia, Costa Rica. The average total length of females was 34.43 +/- 7.26 mm (range 17.80 and 51.50 mm) and the average total weight of 0.69 +/- 0.48 g (range 0.06 and 2.32 g). This species is a viviparous matrotrofic and the specimens were sexually mature. The total length fertility relationship was F = 0.527e 0.1171Lt (r2 = 0.9404). The average fertility was 56.1 +/- 43.6 (eggs + embryos) (range 8.0 and 197.6). The total length-fecundity relationship was Fo = 0.695e(0.1076Lt (r2 = 0.9376). The average fecundity was of 49.0 +/- 36.0 (oocytes + ova) (range 7.0 and 179.0). The total length-gonadosomatic index relationship was IGS = 0.0014 e0.134 Lt (r2 = 0.8581). The average gonadosomatic index was 0.25 +/- 0.27% (range 0.02 and 1.31%). PMID- 17354407 TI - [Culture of Poecilia reticulata (Pisces: Poecilidae) in tropical water bodies, Veracruz, Mexico]. AB - Poecilia reticulata, also known as guppy, is the most popular fish in the aquarium environment. Guppys are viviparous fish with high tolerance to extreme temperatures. The development of the offspring takes between 25 and 30 days. We developed a technology for raising guppys, which outlines infrastructure and devices for reproduction, nursery, feeding, and commercialization, evaluating the financial and technical feasibility of this technology in a case study. The complete reproductive cycle occured in floating cages with 1 mm mesh and the method was tested in a tropical lagoon in Mexico. Water quality was monitored throughout the study period (temperature, dissolved oxygen and pH levels). A marketing survey was carried out at all existing aquarium shops in Veracruz City. Data collected depict quantities demanded and offered for each species by season, place of origin, and resistance to handling. The hydrobiological characteristics were: average temperature 31.4 degrees C, dissolved oxygen 4.5 mgl(-1), and pH level 6.8. With these values we built a production function, and used it to evaluate profitability. We estimate a benefit/cost ratio of 1.16, with a net annual income of US$257.67. The system may provide two permanent jobs. PMID- 17354408 TI - [Feeding habits of the fishes Lutjanus peru and Lutjanus guttatus (Pisces: Lutjanidae) of Guerrero, Mexico]. AB - Diet composition of the Pacific snapper (Lutjanus peru) 130-684 mm fork length (FL) and the spotted snapper (Lugjanus guttatus) 120-550 mm FL, was analyzed. Monthly samples were obtained from commercial landings in three regions off the coast of Guerrero, Mexico. Percentage by number (%N), percentage by weight (%W), and percentage of occurrence (%O) were calculated for each prey and summarized as the index of relative importance. Both species are polyphagous predators feeding on a variety of prey: Sixty-eight prey items, mainly fish (%W = 50.9), crustaceans (%W = 35.6), and mollusks (%W = 7.2), were found in the stomach contents of L. peru, while 88 components were identified in the diet of L. guttatus, the most important prey being fish (%W = 50.8) and crustaceans (%W = 43.4). Diet overlap between species is not significant (p<0.05), indicating that competition for food is unlikely. Based on published values of the relative importance index, the diets of these Lutjanidae were analyzed considering different regions of the Pacific coast of Mexico and Costa Rica, and similarities among sites and species were discussed. The cluster analysis showed that similarities among species inhabiting in the same area are more important than within organisms of the same species living in different zones. Results suggest that prey availability rather than food selectivity, conditions the feeding behavior of these fish species. PMID- 17354409 TI - [Abundance and species richness of fish associated to Thalassia testudinum at Cariaco Gulf, Venezuela]. AB - Fish are among the most abundant and diverse groups in Thalassia testudinum communities, in turn considered among the most productive and important ecosystems in marine environments. Three stations were sampled in the southern shore of Cariaco gulf (northwestern Venezuela) to quantify fish associated with T. testudinum, from December 1996 to November 1997. We used a 50 m long beach net ("chinchorro playero", height 1.50 m, mesh opening 0.7 cm. A total of 15 509 individuals were collected: 27 families, 38 genera and 44 specie were identified. The most abundant, in descending order, were Haemulon boschmae, Nicholsina usta, Orthopristis ruber, Xenomelaniris brasiliensis and Diplodus argenteus. Thirty three species were occasional visitors (75.0%) and ten were recurrent visitors (22.7%). The permanent resident, N. usta, is a characteristic species that uses T. testudinum throughout its life cycle. PMID- 17354410 TI - [Size and age structure of the striped marlin Tetrapturus audax (Pisces: Xiphidae), at Cabo San Lucas, Baja California sur, Mexico]. AB - The striped marlin (Tetrapturus audax) is found in temperate and tropical waters of the Pacific and Indian Ocean. It is particularly abundant in the southern tip of the Baja California peninsula. Specimens brought to Cabo San Lucas port (22 degrees 53' N y 109 degrees 54' W) by the sport fishery fleet that operates withing a radius of 54 km from 1988 to 1993 were sexes, measured and weighed. A total 1030 individuals were sampled. Dorsal fin spines (389) were collected for age estimation. The spines were sectioned and hyaline-opaque bands counted. The relation of length to spine radius was similar for males and females. The fourth dorsal spine reflected the growth of the fish. The rhythm of growth mark formation is yearly and related to the sea surface temperature. Ten age groups were found and the seventh group was the most abundant, followed by groups "6" and "8". The age structure of the striped marlin was stable in the study period. The observed sizes were 160-280 cm jaw length with 90% of the organisms measuring between 190 and 225 cm. The small individuals recruit to the fishery from June to December. PMID- 17354411 TI - Factors associated with the catastrophic decline of a cloudforest frog fauna in Guatemala. AB - Comparison of recent and historical surveys of frog populations in cloudforest habitat in Sierra de las Minas, Guatemala, indicated population declines and local extirpation of several species. Pathological exams of diseased tadpoles indicated infection by amphibian chytridiomycosis. The local habitat has been severely altered by recent establishment of large-scale leatherleaf fern production. Analysis of water chemistry at our study site suggested increased nitrogenation associated with the leatherleaf industry. PMID- 17354412 TI - A twelve-month field study of the west African thrush Turdus pelios (Passeriformes: Muscicapidae). Part 1: food and feeding ecology. AB - The feeding ecology of Turdus pelios was studied from field observations and gizzard contents. Quantitative data on feeding were obtained from repeated standard "fixed route" walks and observational points at seven sites from January to December 1998 on 5065ha at the Obafemi Awolowo University campus, Ile-Ife (7 degrees 20' N, 4 degrees 33' E). Walks (each lasting about two hours) were started at various times of the day between 7.00 and 16.45 h. A total of 100 walks were made and binoculars were used to observe all feeding activities during 10 minutes at each site. Each feeding record included food type, method of feeding and reaction with con-specifics at feeding sites. Gizzards from mist netted specimens were also studied. These birds fed most commonly twice a day between 06.00-9.30 hr in the morning and between 17.00-18.30 hr in the evening. Field observations showed that about 62% of the diet consisted of plant matter. The prey items were earthworms and terrestrial arthropods, of which orthopterans alone constituted 45% of the total. The prey size consumed by both sexes overlapped extensively: differences in prey size were significant only for spiders. PMID- 17354413 TI - Association of the "IUCN vulnerable" spiny rat Clyomys bishopi (Rodentia: Echimyidae) with palm trees and armadillo burrows in southeastern Brazil. AB - The globally vulnerable Clyomys bishopi, a semi-fossorial and colonial rodent, is apparently limited to cerrado (savannah-like vegetation) physiognomies in Sao Paulo State, Brazil. The aim of the study was to verify whether the presence of C. bishopi is associated to the occurrence of palm trees (Attalea gearensis, Syagrus loefgrenii) and armadillo burrows. Thirty six quadrats were placed in different physiognomies of cerrado vegetation at Itirapina Ecological Station, southeastern Brazil to survey the number of C. bishopi burrows of individuals of palm trees and burrows of armadillos. There was a strong dependence and association between the number of C. bishopi burrows and all measured variables (Contingency tables and Spearman rank correlations). It is suggested that this rodent can be found in great numbers where palm trees are abundant. The use of armadillo burrows possibly makes the movement of the rodents easier inside their own galleries. PMID- 17354414 TI - Differences on post-fire regeneration of the pioneer trees Cecropia glazioui and Trema micrantha in a lowland Brazilian Atlantic forest. AB - A study of natural post-fire succession was carried out in a disturbed vegetation around fragments of the Atlantic Rain Forest (National Biological Reserve of Poco das Antas (22 degrees 30'-22 degrees 33'S. 42 degrees 15'-42 degrees 19'W), Rio de Janeiro State). All the pre-fire individuals of Cecropia and Trema in the area were numbered with plastic labels. In order to check for the presence of new sprouts and mortality, two other censuses were carried out, at 3 and 12 months after the fire. The dominant species were: Pteridium aquilinum, Panicum maximum. Trema micrantha and Cecropia glazioui. Few days after the passage of fire, grasses and ferns spread their area, while the stands of Trema and Cecropia were completely burned. Most of individuals of Cecropia produced some sprouts while most of individuals of Trema died. However, a great number of seedlings of Trema were recruited while only one single seedling of Cecropia were observed during a period of one year. Most of these seedlings died through the year while the sprouts were already reproducing. The uses of Cecropia in places where fire is recurrent could be more appropriate because of its higher chance of survival and faster recovering ability after fire. PMID- 17354415 TI - [Phenology of the tree Sideroxylon capiri (Sapotaceae) at the tropical dry forest in Costa Rica]. AB - From March 1996 until February 2000, an study about the phenology of the Tempisque tree [Sideroxylon capiri (A.DC.) Pittier] was made in the Tropical Dry Forest of the Barra Honda National Park (Costa Rica). Ten trees were chosen at random and their phenology was evaluated monthly during the first two years and every two months afterwards. Climatological data were also collected in situ. Trees change their foliage each year during the rainy season or at the beginning of the dry season. In contrast with other native species in forest, soil water deficit is not responsible for foliage change in S. capiri. Some elements that affect the process are photoperiod and herbivores. Unknown physiological mechanisms allow the tree to maintain foliage during the driest months (March and April). Flowering and fruiting may occur every year and in any season, but mostly in the dry season, with variability both among seasons and among individuals. PMID- 17354416 TI - Ultrastructure of Oryza glumaepatula, a wild rice species endemic of tropical America. AB - Orv'za gluniaepatula is a perennial wild rice species, endemic to tropical America, previously known as the Latin American race of Orrza rufipogon. In Costa Rica, it is found in the northern region of the country, mainly in the wetland of the Medio Queso River, Los Chiles, Alajuela. It is diploid, of AA type genome and because of its genetic relatedness to cultivated rice it is included in the O. saliva complex. We describe the ultrastructure of leaf blade, spikelet, ligule and auricles. Special emphasis is given to those traits of major taxonomic value for O. glumaepatula and to those characters that distinguish this species from O. rufipogon and O. sativa. O. glumaepatula has a leaf blade covered with tombstone shaped, oblong and spheroid epicuticular wax papillae. It has diamond-shaped stomata surrounded by spherical papillae, rows of zipper-like silica cells, bulky prickle trichomes of ca. 40 microm in length and small hirsute trichomes of ca. 32 tpm in length. The central vein is covered with large, globular papillae of ca. 146 microm in length, a characteristic that distinguishes this species from O. rufipogon and O. sativa. The border of the leaf blade exhibits a row of even sized bulky prickle trichomes of ca. 42.5 microm in length. Auricles have attenuated trichomes of ca. 5.5 mm in length on the edges and small bicellular trichomes of 120 microm in length on the surface. The ligule has a large number of short attenuated trichomes on its surface of 100 microm in length. These latter two traits have important taxonomic value since they were found in O. glumaepatula but not found in O. sativa or in O. rufipogon. The spikelet has the typical morphology of the Oryza genus. Fertile lemmas have abundant spines, a trait shared with O. rufipogon but not with O. sativa. The sterile lemmas are wing-shaped with serrated borders, a characteristic that distinguishes this species from O. rufipogon and O. sativa. All the ultrastructure characters observed in O. glumaepatula from Costa Rica are also common to the specimens from Brazil. PMID- 17354417 TI - Specific leaf mass, fresh: dry weight ratio, sugar and protein contents in species of Lamiaceae from different light environments. AB - Samples from eleven species of Lamiaceae were collected from different light environments in Venezuela for laboratory analysis. The studied species were: Plectranthus scutellarioides (Ps), Scutellaria purpurascens (Sp), Hyptis pectinata (Hp)), H. sinuata (Hs). Leonorus japonicus (Lj), Plecthranthus amboinicus (Pa) Ocimum hasilicum (Ocb), O. campechianum (Occ) Origanum majorana (Orm), Rosmarinus officinali, (Ro) and Salvia officinalis (So). Protein and soluble sugar contents per unit of area were measured, Specific Leaf Mass (SLM) and fresh:dry weight (FW/DW) ratios were calculated. The higher values for soluble sugars contents were present in sun species: Lj, Pa, Ocb, Occ, Orm, Ro and So; the lower values were obtained in low light species: Ps, Sp, Hp, Hs. The values of protein content do not show any clear trend or difference between sun and shade environments. The lowest values for the fresh weight: dry weight ratio are observed in sun species with the exception of Lj and Pa, while the highest value is observed in Pa, a succulent plant. The higher values of specific leaf mass (SLM) (Kg DMm(-2)) are observed in sun plants. The two way ANOVA revealed that there were significant differences among species and between sun and low light environments for sugar content and FW:DW ratio. while SLM was significant for environments but no significant for species, and not significant for protein for both species and environments. The soluble sugar content, FW:DW ratio and SLM values obtained in this work, show a clear separation between sun and shade plants. The sugar content and FW:DW ratio are distinctive within the species, and the light environment affected sugar content. FW:DW ratio and SLM. These species may he shade-tolerant and able to survive in sunny environments. Perhaps these species originated in shaded environments and have been adapting to sunny habitats. PMID- 17354418 TI - Secondary stem anatomy and uses of four drought-deciduous species of a tropical dry forest in Mexico. AB - Wood and bark anatomy and histochemistry of Acacia bilimekii Humb. & Bonpl., Acacia cochliacantha Mcbride, Conzatia nultiflora (Rob) Stand. and Guazuma ulmifolia Lam. are described from stem samples collected in a tropical dry forest (Morelos, Mexico). Enzyme activities were tested in tangential, radial and transverse cuts of fresh material. Histochemistry and stem anatomy were studied on similar cuts previously softened in a solution of water-glicerol-PEG. Our results show that the anatomical patterns of bark and wood, as well as the histochemical patterns and specific gravity, are influenced by water accessibility and climate; these patterns could guarantee mechanical and anti infection strategies to support extreme conditions. Enzyme cytochemistry reveals biochemical activities probably related to lipid utilization routes for the lignification processes and for synthesis of extractives; these results suggest that the formation and maturation of woody tissue is very active at the beginning of the rainy season. These species are widely used by the local population. Traditional uses include firewood, dead and live fences, fodder, construction, supporting stakes, handcrafts, farming tools, extraction of tanning products, and medicine. There is no relationship between use and abundance. Alternative uses are proposed according to a density index. PMID- 17354419 TI - Floral biology and reproductive system of enantiostylous Senna corymbosa (Caesalpiniaceae). AB - The genus Senna (K. Bahuin) Miller (Cassieae) is represented in Argentina by 35 species and several varieties distributed in temperate, tropical and subtropical regions, and presents a high degree of endemism. Some taxa are used for medicine, animal foraging and ornamental purposes. Floral morphology, phases, rewards, attractants, visitors, pollen, reproductive system, P/O ratio. OCI and ISI indexes of enantiostylous Senna corymbosa were analyzed for morphological androecial differentiation and possible related functional differences between stamens groups. The study was carried out over three consecutive flowering seasons in March of 1999, 2000 and 2001, in two populations near the city of Buenos Aires, Argentina. The species has a buzz-pollination syndrome. The pollinators are Bombus atratus that vibrate the stamens, leading to nothotribic or stemotribic deposition of pollen. P/O ratio and pollen production were high thanks to the precise pollinating mechanism that needs a large delivery of pollen to ensure effective pollen deposition. P/O ratio also indicates that the species is xenogamous, although geitonogamy and autogamy (only induced, not spontaneous) were also recorded. The species is self-compatible. There were differences in hand-pollination treatments between long and medium stamens in fruit set, as well as in vitro differential fertility between their pollen grains. Hence, there are morphological and functional androecium differences: the medium stamens play a nutritional role while the long ones play a reproductive one. These differences are reflected in the breeding system. Moreover, differential fertility and enantiostyly may diminish the effects of self-compatibility by partially reducing the contribution of geitonogamy to selfing. PMID- 17354420 TI - [The seeds of Campsiandra angustifolia (Fabaceae: Caesalpiniodeae) as a reflex of selective pressures on dispersal and establishment]. AB - We indirectly evaluated the selective pressures on dispersal and establishment of Campsiandra angustifolia, a common water-dispersed tree from the Peruvian Amazon, analyzing the variation in the relationship between the volume occupied by dispersal and establishment structures in a total of 535 seeds from 13 trees located at three different habitats. The seeds differed one order of magnitude in their total volume. However, independently of their size and the location of the maternal tree, the relationship between the volume occupied by dispersal and establishment structures was relatively constant (approximately 1) and showed a normal distribution with low skewness, indicating stabilizing selection. These results suggest that, in the habitats studied, dispersal and establishment processes may have similar importance to C. agustifolia. In species with seeds confined in pods, and therefore strongly space-limited, the relative volume of their seeds occupied by dispersal and establishment structures could be a better measure of the trade-off between these two processes than the variation in seed size. PMID- 17354421 TI - [Orchids from coffee-plantations in mexico: an alternative for the sustainable use of tropical ecosystems]. AB - Life form, endemism, conservation status, and horticultural interest are detailed for orchid species associated to shade coffee-plantations in Mexico. About 11% of the orchid taxa (214 species) found in these agroecosystems are in the Mexican list of species requiring some form of protection. Almost 40% of the species are of horticultural interest. The importance of promoting shaded coffee plantations as an alternative to the conservation of primary plant communities in Mexican and other tropical regions is clear. Long term management plans are recommended. PMID- 17354422 TI - Trophic interactions within the microbial food web in a tropical floodplain lake (Laguna Bufeos, Bolivia). AB - Whether the primary role of bacterioplankton is to act as "remineralizers" of nutrients or as direct nutritional source for higher trophic levels will depend on factors controlling their production and abundance. In tropical lakes, low nutrient concentration is probably the main factor limiting bacterial growth, while grazing by microzooplankton is generally assumed to be the main loss factor for bacteria. Bottom-up and top-down regulation of microbial abundance was studied in six nutrient limitation and dilution gradient-size fractionation in situ experiments. Bacteria, heterotrophic nanoflagellates (HNF), ciliates and rotifers showed relatively low densities. Predation losses of HNF and ciliates accounted for a major part of their daily production, suggesting a top-down regulation of protistan populations by rotifers. Phosphorus was found to be strongly limiting for bacterial growth, whereas no response to enrichment with Nitrogen or DOC was detected. HNF were the major grazers on bacteria (g-0.43 d( 1)), the grazing coefficient increased when ciliates were added (g- 0.80 d(-1)) but decreased when rotifers were added (g- 0.23 d(-1)) probably due to nutrient recycling or top-down control of HNF and ciliates by rotifers. PMID- 17354423 TI - [Spatial and biogeographic characterization of macroalgal assemblages from Bahia del Rincon, Baja California Sur, Mexico]. AB - Macroalgal studies in Baja California Sur have dealt mainly with occurrence and seasonality, but some areas are poorly known even for these basic data. Bahia del Rincon-La Rivera is an important high-productivity fisheries area where coastal infrastructure development is under way. A spatial characterization of the marine flora from Bahia del Rincon-La Rivera was done by intensive sampling at different depths and localities with skin and SCUBA diving. At least 500 m2 were surveyed in each site. Additionally. quantitative sampling was done in ten random 25 cm2 quadrates per site. In the intertidal section, density and cover estimates were used. We also investigated the historical records and geographical affinities. A total of 72 species were identified (most were red algae: 62%). We found no general trend in the biogeographical affinities, which varied with each taxonomic group. Most brown algae species were tropical-endemic; red algae temperate cosmopolite and green algae tropical-cosmopolite. In the spatial assemblage structure we found a high similarity between the intertidal areas, but a low similarity in shallow or deeper areas (3-5 m). This pattern was the same when we compared the abundance of the main species. We suggest that there are significant spatial differences in recruitment and development of the assemblages in relation to vertical distribution (depth) and position along the shore. There is a clear cut Gelidium-Jania belt in the intertidal zone and a Padina-Dictyota belt below the low tide. Sporadic and year-round species occur in the intertidal zone, annual and perennial species below the low tide line. Sites differ in recruitment and this affects the abundance of other species (such as coraline and Caulerpa species). Temperature and sedimentation affect seasonality, but community structure is relatively constant throughout the year. PMID- 17354424 TI - [Comparison between two methods to measure herbivory. Is herbivory in the neotropics more severe than we thought?]. AB - The quantity of plant tissue consumed by herbivores can be recorded 1) by measuring herbivory in previously marked leaves or 2) by performing punctual measures. i.e. selecting leaves at random to measure the tissue absent in each leaf Punctual measurements are frequently used because they are a faster method to estimate herbivory. However, punctual measures do not include totally consumed leaves. therefore they underestimate the actual herbivory rates. In three species of understory shrubs (Palicourea sp. P. angustifolia and P. oralis: Rubiaccae) herbivory was measured using punctual measures and marking young leaves in order to determine the degree of herbivory underestimation by punctual measurements. Punctual measurements underestimated herbivory up to three times in the species with a high number of totally consumed leaves. In the species with a lower number of totally consumed leaves, herbivory rates recorded using both methods were similar. These results suggest that herbivory in neotropical forests could be more severe than what is currently suggested. PMID- 17354425 TI - [Influence of environmental factors on the distribution of tree species in the forests of south-eastern Mexico]. AB - We studied the relationship between the distribution of tree species and environmental factors in the Sian Ka'an Biosphere Reserve, south-eastern Mexico. Our main objective was to examine how changes in microtopography and edaphic factors influence the distribution of tree species of medium and low-statured forests. We established 17 plots of 625 m2 and collected data on spatial distribution of individuals with dbh > or = 5 cm, and the following soil variables: electric conductivity (CE), cationic exchange capacity (CEC), textural class, pH, organic matter (MO), total nitrogen (Nt) and phosphorus availability (P). We used Twinspan to classify the plots and applied indirect (DCA) and direct (CCA) gradient analysis. We found 84 species and 4 433 individuals. MO, texture and CEC varied significantly (p< or =0.05) between the high and low parts. DCA and CCA indicated that the species distribution is strongly influenced by the microtopography gradient and the textural class. Using DCA and CCA exclusively on the data of the low parts, two low statured forest types were identified: one characteristic of low zones (soil slightly basic and high percentage of clay), the other surrounded by medium statured forest (soil slightly acid, high CEC, MO and clay). PMID- 17354426 TI - [Diversity and abundance of mollusks in the sublittoral epifaunal community of Punta Patilla, Venezuela]. AB - The diversity of a sublittoral epifaunal mollusk community of Punta Patilla, Sucre State, Venezuela, was studied from September 1990 to September 1991. We identified 25 species (14 bivalves and 11 gastropods) of mollusks that inhabit gravel, soft sand and bottoms covered by Thalassia testudinum. Total diversity indices were H' = 3.42. J' = 0.74 and 1-D = 0.85. Monthly diversity reached its maximum in March 1991 (3.12 bits/ ind.), June 1991 (2.88 bits/ind.) and September 1991 (2.95 bits/ind.); minimum diversity was recorded in August 1991 (1.20 bits/ind.). A log series model showed a diversity index alpha = 4.56 for species abundance data and alpha = 3.11 for biomass data. The more abundant species were Chione cancellata, Anigona listeri, Chione granulata and Area zebra among the bivalves, and Chicoreus brevifrons, Turritella variegata and Phllonotus pomum among the gastropods (which present maximum biomass). The average total biomass (56.80 g/m2) is low when compared to reports from other tropical zones. PMID- 17354427 TI - [Toxic effect of DDT and endosulfan in white shrimp postlarvae Litopenaeus vannamei (Decapoda: Penaeidae) from Chiapas, Mexico]. AB - We analized acute toxicity in white shrimp (Litopenaeus vannamei) postlarvae exposed to two chlorinated pesticides, DDT and endosulfan, under laboratory conditions during 168 hours, with controlled temperature (29 +/- 1 degrees C), salinity (3 +/- 1%o) and pH (8 +/- 1). Median lethal concentrations (LC50), "incipient" LC50, median lethal time (LT50) the "maximum acceptable concentration of the toxic compound" (MACT) and "the safety level" (SL) were determined. The concentration of the compounds at which organism growth was reduced by 5 and 50% (EC5 and EC50), as well as changes in oxygen consumption patterns were determined in the surviving postlarvae. They were very sensitive to both compounds and DDT was thrice as toxic as endosulfan. Growth rate decreased 50% and 80% with endosulfan and DDT, respectively, at the experimental pestice concentration. The low resistance of postlarvae to DDT and endosulfan suggests that additional inflow of these pesticides into the aquatic system could affect the rate of shrimp production in the area. PMID- 17354428 TI - [Egg morphology of seven noctuid species (Lepidoptera: Noctuidae) from Chilean and updated key to their identification]. AB - Eggs from seven Noctuid moth species, Eriopyga perfusca (Hampson), Magnagrotis oorti (Koehler), Pseudoleucania brosii (Koehler), Scania simillima (Koehler). Scriptania americana (Blanchard), Scriptania leucofasciata Rodriguez, were collected at La Mina, 925 msnm, (35 degrees 21' S; 71 degrees 41' W) and Paso Internacional Pchucnche (35 degrees 57' S: 70 degrees 23' W), 2560 msnm, Chile. The Scanning Electron Microscope showed that egg morphology allows identification to species level. This is particularly useful in agricultural pest control, and morphological differences are used in this report to present an updated taxonomic key to the Chilean Noctuidae. PMID- 17354429 TI - Diversity of the ground-dwelling ant fauna (Hymenoptera: Formicidae) of a moist, Montane forest of the semi-arid Brazilian "Nordeste". AB - Although the so called "green islands" of the semi-arid Brazilian "Nordeste" are economically, socially, and ecologically important. relatively little is known about their biodiversity. We present the results of the first survey of the ground-dwelling ant fauna of a secondary forest in the Serra de Baturite (4 degrees 05'-4 degrees 40' S / 38 degrees 30'-39 degrees 10' W), among the biggest of the moist, montane forests of the state of Ceara, Brazil. From February to March 2001, samples were taken every 50 m along twelve 200 m transects, each separated from the others by at least 50 m and cut on either side of a recreational trail. Where possible, two transects were cut from the same starting point on the trail, one on either side. At each sample site two methods were used, as recommended in the ALL. protocol: a pitfall trap and the treatment of 1 m2 of leaf litter with the Winkler extractor. The myrmecofauna of the Serra de Baturite is quite diverse: individuals from 72 species, 23 genera, and six subfamilies were collected. The observed patterns of specific richness show the same tendencies noted in other tropical regions, particularly the frequency of capture distribution with many rare and few abundant species. Differences with the Atlantic and Amazonian forests were also observed, especially the relative importance of the Ponerinac and Formicinae subfamilies, indicating a possible influence of the surrounding "caatinga" (savanna-like ecosystem) on the myrmecofauna of the moist, montane forest. PMID- 17354430 TI - Nesting biology of four Tetrapedia species in trap-nests (Hymenoptera: Apidae: Tetrapediini). AB - The nests used in this study were obtained from trap-nests (tubes of cardboard and cut bamboo stems) placed on Santa Carlota Farm (Itaoca Section-IS, Santana Section-SS and Cerrado-Ce), Cajuru, SP, Brazil. The number of nests and corresponding species obtained were as follows: 516 nests of T. curvitarsis, 104 of T. rugulosa, 399 of T. diversipes and 98 of T. gamfaloi. The most abundant species from SS and Ce was T. curvitarsis, and from IS it was T. diversipes. In general, most nests were collected during the hot and wet season (September to April). The nests were constructed with sand and an oily substance, and a single female established them. The cells were constructed in a linear series, sometimes followed by a vestibular cell. The number of brood cells ranged from 1 to 10 in T. curvitarsis (n=200), and in T. garofaloi (n-51), from 1 to 8 (n-30) in T. rugulosa, and from 1 to 6 (n=37) in T. diversipes. The pollen mass (pollen + oily substance) contained a hollow, sometimes divided by a transverse ridge, on the exposed face of the pollen mass. The egg was vertically positioned in the lower part of the hollow. At times, the closing of a cell was initiated before provisioning was completed, with a construction of a collar at the cell limit. In some nests the final cellular partition also acted as a closure plug. Females began activities at 6:18 a.m. and ended between 3:31 and 6:26 p.m. Some females (T. curvitarsis, T. rugiulosa and T. ganrfaloi) did not spend the nights at their nests, returning to them only the following morning with additional material. In general, the development period (for males and females) was greater in nests collected near the end of the hot and wet season than it was for nests collected in other months. Sex ratios for each species were as follows: T. curvitarsis. 1:1: T. rugulosa, 1.6:1 female; T. diversipes, 1.9:1: T. garofaloi, 2.8:1. Males and females of T. diversipes exhibited statistically similar sizes and in the other three species the females were larger than the males. The mortality rates were statistically similar: 33.2% for T. curvitarsis, 25.8% for T. rugulosa, 26.8% for T. diversipes and 38.2% for T. garnfaloi. The parasitoids were: Coelioxoides exulans, Leucospis cayenensis, Anthrax sp., Coelioxys sp., Coelioxoides sp. and individuals of the family Meloidae. PMID- 17354431 TI - [Life table for Selenothrips rubrocinctus (Thripidae: Panchaetothripinae) under laboratory conditions]. AB - The tropical thrip Selenothrips rubrocinctus Giard is a polyphagous species sometimes found in commercially important crops that include cocoa and cotton. Laboratory data from specimens collected in Psidium friedrichsthalianum trees in Costa Rica were used to prepare a life table. There was a high mortality in the egg (72.5%) and larva II (18.4%) stages. On leaves, inmature stages presented subvascular distribution and pupae presented submarginal distribution. PMID- 17354432 TI - [A new species of thrip, genus Frankliniella (group Cephalica; Thysanoptera: Thripidae) from Costa Rica]. AB - A new species of the Frankliniella cephalica group, from Central Costa Rica, is described under the name "Frankliniella morerai n.sp.". It is closely related to Frankliniella sandovalensis. Both species have translucent bodies, but the new species can be distinguished by these characteristics: setae io II in position 1/2, a complete comb on abdominal segment VIII, antennal segments without coloration and setae po IV longer. It was found in low density in crops of chilli, tomato, lettuce, sweet potato and coriander. A comparative table with other species of this group is included to facilitate diagnosis. PMID- 17354433 TI - [Trophic ecology and reproductive aspects of Trichomycterus areolatus (Pisces, Trichomycteridae) in irrigation canal environments]. AB - Twelve of the sixteen species of fishes present in the Itata river basin enter the irrigation canals at least once a year, constituting a habitat that is frequently utilized by the native fish assemblages. However, only Trichomcterus areolatus, a native siluriform, is found in great number throughout the entire year, being the dominant species of such artificial environments. Among the factors that could explain the relative success of T. areolatus are its benthonic habits, adaptation to rithral habitat, an offer of trophic resources that is in line with its feeding habits, and a lower abundance of predators in the canals. In this study, the trophic ecology of this species in 174 individuals inhabiting the Itata river (Octava Region, Chile) and 231 from irrigation canals that arise from this river are analyzed and compared. In addition, the length-weight relationship and seasonal frequencies of reproductive status are analyzed, with the purpose of inferring on the status of these populations and their possible condition of resident in these canals. In canals, its diet includes a greater number of different taxa as well as total number of preys consumed in comparison with the river populations, including items of greater biomass, such as lumbriculides. The selectivity analysis showed that T. areolatus prefer prey items like Chironomidae, Baetidae, Elmidae, Plecoptera and Hyallela. Although both the river as well as canal populations show an isometric type growth, they reach greater body lengths and weights in the latter. According to the reproductive states analysis in different periods of the year, populations inhabiting canal environments reproduce synchronically with those of the river, although these latter tend to show a slight delay in the reproductive activity. PMID- 17354434 TI - [Gross morphometry of young Geochelone sulcata (Testudines: Testudinidae) in Costa Rica]. AB - The African Spur tortoise, Geochelone sulcata, has been introduced to Costa Rica. A total of 31 tortoises were measured for 26 gross morphometry parameters. All individuals measured were inmature, aged from 5 to 34 months, and were born in captivity in La Garita de Alajuela, Costa Rica. Mean straight carapace length was 83.1 mm, mean straight plastron length was 68.3 mm and mean maximum height was 46.2 mm. All the measurements were correlated, except tail length and cloacal distance. Weight had the highest positive allometry coefficient. All the variables were joined in two Principal Components; tail length and cloacal distance in Factor 2 and the rest of them in Factor 1. Lack of correlation among tail measures and the other variables as well as their inclusion in a different Factor could be related with an incipient development of sexual dimorphism characters. PMID- 17354435 TI - [A fish prey found in the coral snake Micrurus alleni (Serpentes: Elapidae) in Costa Rica]. AB - A fish prey found in the coral snake Micrurus alleni (Serpentes: Elapidae) in Costa Rica. The presence of a small specimen of the swamp eel Synbranchus marmoratus (84 mm total length) in the stomach contents of an adult coral snake Micrurus alleni with 692 mm total length from the Caribbean versant of Costa Rica is reported. This eel was swallowed headfirst. PMID- 17354436 TI - [Water birds from Agua Dulce lake and El Ermitano estuary, Jalisco, Mexico]. AB - Waterbird abundance, and seasonal and spatial distribution, were studied in two natural water pools at Jalisco, Mexico, from December 1997 through November 1998. Maximum monthly abundance in Agua Dulce lake and El Ermitano estuary was 86 471 birds (29 686 in Agua Dulce and 56 785 in Ermitano), with a total cummulative abundance of 179 808 individuals (66 976 in Agua Dulce and 112 832 in Ermitano). A total of 87 waterbirds species were recorded, 78 in Agua Dulce and 73 in Ermitano. The higher species richness and abundance was observed during winter, when migratory species arrived. Most species prefered shallow waters, except seabirds which prefered protected areas such as dunes in Agua Dulce. Other groups, like clucks and related species. prefered low salinity areas, for example in the south-east area of Ermitano. The higher abundance of the shorehirds was found when the water level on the estuary was low. Herons were seen often at areas with high salinity and influenced by tides (e.g. mouth of Ermitano). PMID- 17354437 TI - A twelve-month field study of the West African thrush Turdus pelios (Passeriformes: Muscicapidae). Part 2: annual cycles. AB - In Africa, birds inhabiting forested regions are less seasonal in their activities than those from open areas. In order to study annual cycles in forest regions of South western Nigeria, West African Thrushes (Turdus pelios) were mist netted and banded during the last two weeks of each month. The nest is a cup shaped structure built out of grasses, herbs, weeds, roots and earth laid out in a clockwise manner. Only the nesting tree and feeding sites were defended during the breeding period. The clutch size was 2.69 +/- 0.20 eggs with a mean incubation period of 14.11 +/- 0.26 days. The mean nestling period was 15 +/- 1.00 days. The nestlings were fed on a variety of plant and animal matter, of which grass seeds and insects were predominant. Moult was found to be protracted with a population moult period of 194 days and a much shorter individual moult period. Moult and breeding periods were spread out: moult period dovetailed into the breeding period. The birds were found to gain weight during the period but they attained their maximum weight in August after the moult period. The lowest weight was recorded in February, during the peak of the dry season, when food availability was lower. PMID- 17354438 TI - Patterns of cetacean sighting distribution in the Pacific exclusive economic zone of Costa Rica based on data collected from 1979-2001. AB - Nineteen species of cetaceans (families Balaenopteridae, Kogiidae, Physeteridae, Ziphiidae and Delphinidae) occur in the Costa Rican Pacific Exclusive Economic Zone (EEZ). Based on data recorded from the EEZ by the Southwest Fisheries Service Center, Cascadia Research Collective, and CIMAR between 1979-2001, we mapped the distribution of 18 cetacean species. Our results suggest that the majority of the cetacean species use primarily oceanic waters, particularly those species within the families Balaenopteridae, Kogiidae. Physeteridae and Ziphiidae. Members of the family Delphinidae showed a wide variety of distribution patterns: seven species are widespread throughout the EEZ, four appear to be exclusively pelagic, and two are primarily coastal. Overall, three cetacean species appear to have populations concentrated in coastal waters: Stenella attenuata graffmani. Tursiops truncatus, and Megaptera novaeangliae. These three may be more susceptible to human activities due to the overlap of their ranges with fishery areas (tuna and artisanal fisheries), and an uncontrolled increase of touristic whale watching activities in several parts of their range. The distribution maps represent the first comprehensive representation of cetacean species that inhabit Costa Rican Pacific waters. They provide essential base-line information that may be used to initiate conservation and management efforts of the habitats where these animals reproduce and forage. PMID- 17354439 TI - [Occurrence and behavioral patterns of the spotted coastal dolphin Stenella attenuata (Cetacea: delphinidae) in the Gulf of Papagayo, Costa Rica]. AB - Dolphins are characterized by a significant behavioral versatility, which allows them to respond to environmental seasonality. Seasonal variation in dolphin behavior in tropical waters is not well known. Stenella attenuata graffmani is a resident dolphin in the clearly defined seasonal Gulf of Papagayo, Costa Rica, and we studied if dolphin group size, occurrence and behavioral patterns were associated with season and time of day in the gulf. Using strip transects we surveyed two locations for three consecutive years. School size ranged from 1 to 50 individuals, mean group size was 10.16 (SD = 9.61) individuals. Overall, foraging activities were the most frequent, followed by social interactions and travel. From 6:00 AM to 9:00 AM we mostly observed social interactions, followed by feeding-socializing (9:00 AM-12:00 PM) and feeding exclusively (12:00 PM-3:00 PM). Social activities intensified afterwards (3:00 PM-6:00 PM). Behavior and gulf seasonality were associated (chi2 = 90.52, gl = 6, p<0.05, n = 99). In the dry season (December-April) feeding predominated over other activities, but socializing was more frequent in the early rainy season (May-July). Larger groups (mean 12 dolphins) forage actively; smaller groups (mean 6 dolphins 6.51 +/- 5.12) foraged more passively. Seasonal variation in dolphin activities are likely to be associated with food availability, as observed in the high number of groups involved in foraging behaviors, and a high investment in foraging activities during the dry season. PMID- 17354440 TI - [Digestibility of columnar cacti pollen grains in the glosophagine bats Glossophaga longirostris and Leptonycteris curasoae (Chiroptera: Phyllostomidae)]. AB - We examined the protoplasmic assimilation of columnar cacti pollen grains in two species of Venezuelan desert glosophagine bats, Glossophaga longirostris and Leptonycteris curasoae, by determining the amount of empty (digested) pollen grains found in their fecal samples. To determine the amount of empty pollen grains, the fecal samples were stained to differ between empty and full (non digested) pollen grains. The number of empty and full pollen grains observed in the fecal samples were corrected using the amount of aborted pollens present (before anthesis) in flowers of the columnar cacti species (Subpilocereus repandus, Stenocereus griseus and Pilosocereus tillianus) used by bats as food in the study site; G. longirostris and L. curasoae digested 64.2% and 71.3% of all the pollens fed, respectively. These high values confirm the importance of pollen in the diet of these bats, given its high nitrogen level. PMID- 17354441 TI - The countries and languages that dominate biological research at the beginning of the 21st century. AB - Traditionally, studies of scientific productivity are biased in two ways: they are based on Current Contents, an index centered in British and American journals, and they seldom correct for population size, ignoring the relative effort that each society places in research. We studied national productivity for biology using a more representative index, the Biological Abstracts, and analyzed both total and relative productivity. English dominates biological publications with 87% (no other individual language reaches 2%). If the USA is considered a region by itself, it occupies the first place in per capita production of biology papers, with at least twice the productivity of either Asia or Europe. Canada, Oceania and Latin America occupy an intermediate position. The global output of scientific papers is dominated by Europe, USA. Japan, Canada, China and India. When corrected for population size, the countries with the greatest productivity of biology papers are the Nordic nations, Israel, Switzerland, Netherlands, Australia, Saint Lucia and Montserrat. The predominance of English as the language of biological research found in this study shows a continuation of the trend initiated around the year 1900. The large relative productivity of the USA reflects the importance that American society gives to science as the basis for technological and economic development, but the USA's share of total scientific output has decreased from 44% in 1983 to 34% in 2002, while there is a greater growth of science in India, Japan and Latin America, among others. The increasing share obtained by China and India may reflect a recent change in attitude towards funding science. The leadership of Nordic nations, Israel, Switzerland, Netherlands and Australia can be explained by cultural attitude. Apparently, a positive trend is emerging in Latin America, where Chile improved its ranking in per capita productivity but Argentina, Costa Rica, Uruguay, Brazil and Cuba fell. Nevertheless, the most productive countries in total number of papers are Brazil, Mexico and Argentina: large countries with a long tradition of funding scientific research. PMID- 17354442 TI - [Association of the p53 codon 72 polymorphism to gastric cancer risk in a hight risk population of Costa Rica]. AB - Gastric cancer is the second most common cancer associated death cause worldwide. Several factors have been associated with higher risk to develop gastric cancer, among them genetic predisposition. The p53 gene has a polymorphism located at codon 72. which has been associated with higher risk of several types of cancer, including gastric cancer. The aim of this study was to determine the association of p53, codon 72 polymorphism. with the risk of gastric cancer and pre-malignant lesions in a high-risk population from Costa Rica. The genotyping was carried out by PCR-RFLP in 58 gastric cancer patients, 99 controls and 41 individuals classified as group I or II. according to the Japanese histological classification. No association was found for p53. codon 72 polymorphism with neither the risk of gastric cancer nor the risk of less severe gastric lesions in the studied population. Based on this study and taking into account other studies carried out with p53, codon 72 polymorphism. the role of this polymorphismn in the development of gastric cancer remains unclear. De novo mutations on p53 gene produced during neoplasic development of this disease might play a greater role than germinal polymorphisms of the gene. Other polymorphic genes have been associated with higher risk to develop gastric cancer. PMID- 17354443 TI - [Effect of heavy metals on the growth of tropical microalga Tetrasermis chuii (Prasinophyceae)]. AB - We determined the toxic effect of four metals, cadmium (Cd), copper (Cu), mercury (Hg) and lead (Pb), on the tropical microalga Tetraselmis Chuii (Butcher, 1959). We exposed 50 ml of cultivated microalgae (f/2 Guillard) in the exponential growth phase, with three replicates, to concentrations of 0 (control). 0.1, 1.0, 5.0, 10.0 and 20.0 mgxl(-1) with each metal for 96 hr. We evaluated the lethal effect daily, through the cellular count. In the control treatment (not exposed to any metal) we observed an increase in cellular density. In all treatments exposed to metals, we observed a decrease in cellular density, which accelerated in 48 h, after which it became less pronounced. There were exceptions with low concentrations of Cd and Cu at 24 h, as there was no significant decrease, probably due to their use as micronutrients at these low concentrations. The metal that caused the most lethal effect was Pb, which killed 50% of the microalgal population at a concentration of 0.40 mg x l(-1). This concentration was 3 times lower than that of mercury and 13 times lower than those of cadmium and copper. The microalga Tetraselmis chuii is recommended as a model species to estimate the toxic effects of xenobiotics on tropical seawater environments. PMID- 17354444 TI - [Carotenogenesis of five strains of the algae Dunaliella sp. (Chlorophyceae) isolated from Venezuelan hypersaline lagoons]. AB - We evaluated discontinuous cultures (Algal medium at 0.5 mM of NaNO3, and 27% NaCI) of five strains of Dunaliella sp. isolated from Venezuelan hypersaline lagoons (Araya, Coche, Peonia, Cumaraguas. and Boca Chica) and one strain from a reference collection (Dunaliella salina, LB1644). Cultures were maintained to 25+/-1 degrees C, with constant aeration, photoperiod 12:12, and two light intensities (195 and 390 microE.m(-2).s(-1)) during 30 days. Cell count was recorded on a daily basis using a Neubauer camera. Totals of chlorophyll a and carotenoids were measured at the end of the experiment. The largest cellular densities were measured during the smallest light intensities. The strain with the largest cellular density was isolated from Boca Chica (8 xl0(6) and 2.5 xl0(6) cel.ml(-1) a 390 and 195microE.m(-2).s(-1), respectively). The increment of light intensity produced a significant reduction of growth rates in all strains. Totals of carotenoids by volume were as large as 390 microE.m(-2).s(-1). Strains LB 1644, from Coche and Araya were those that produced the largest amount of carotenoids (38.4; 32.8 and 21.0 microg.ml(-1), respectively). Differences total carotenoids by cell between treatments were significant. The largest concentration was 390 microE.m(-2).s(-1). The strains LB 1644 and Coche produced the highest values of carotenes (137.14 and 106.06 pg.cel(-1), respectively). Differences in the relation carotenoid:chlorophyll a between the strains at various light intensities was significant. Strains LB1644 presented the largest value of the relation carotenoids:chlorophyll a (20:1) at 195 microE.m(-2).s(-1). No significant differences were detected in the strain Coche (15:1). All the other strains showed relations lower than one. Our results suggest that the strains of Coche and Araya show potential to be used in the biotechnology of carotenoids production. PMID- 17354445 TI - [Effect of the spatial and seasonal soil heterogeneity over arbuscular mycorrhizal fungal spore abundance in the semi-arid valley of Tehuacan-Cuicatlan, Mexico]. AB - Recent studies have shown that some species of Mimosa (Leguminosae-Mimosoideae) create resource islands (RI), rich in soil organic matter and nutrients, as well as in arbuscular mycorrhyzal fungal (AMF) spores, in the semi-arid Valley of Tehuacan-Cuicatlan. The relevance of this fact is that arid and semi-arid regions are characterized by low fertility soils and scarce precipitation, limiting plant species growth and development; this explains why the presence of AM fungi may be advantageous for mycorrhizal desert plants. Fluctuations in AMF spore numbers could be related to environmental, seasonal and soil factors which affect AMF sporulation, in addition to the life history of the host plant. The aim of this study was to asses the impact of spatial (resource islands vs open areas, OA) and seasonal (wet season vs start of dry season vs dry season) soil heterogeneity in the distribution and abundance of AMF spores in four different study sites within the Valley. We registered AMF spores in the 120 soil samples examined. Significant differences in the number of AMF spores were reported in the soil below the canopy of Mimosa species (RI) comparing with OA (RI > OA), and between Mimosa RI themselves when comparing along a soil gradient within the RI (soil near the trunk > soil below the middle of the canopy > soil in the margin of the canopy > OA); however, there were no significant differences between the soil closest to the trunk vs middle, and margin 's OA. Finally, more spores were reported in the soil collected during the wet season than during the dry season (wet > start of dry > dry). Therefore, the distribution of AMF spores is affected by spatial and seasonal soil heterogeneity. This study points out the relevance of Mimosa RI as AMF spore reservoirs and the potential importance of AM fungi for plant species survivorship and establishment in semi-arid regions. AM fungi have recently been recognized as an important factor determining plant species diversity in arid and temperate ecosystems. PMID- 17354446 TI - Nitrogen and phosphorus resorption in a neotropical rain forest of a nutrient rich soil. AB - In tropical forests with nutrient-rich soil tree's nutrient resorption from senesced leaves has not always been observed to be low. Perhaps this lack of consistence is partly owing to the nutrient resorption methods used. The aim of the study was to analyse N and P resorption proficiency from tropical rain forest trees in a nutrient-rich soil. It was hypothesised that trees would exhibit low nutrient resorption in a nutrient-rich soil. The soil concentrations of total N and extractable P, among other physical and chemical characteristics, were analysed in 30 samples in the soil surface (10 cm) of three undisturbed forest plots at 'Estaci6n de Biologia Los Tuxtlas' on the east coast of Mexico (18 degrees 34' - 18 degrees 36' N, 95 degrees 04' - 95 degrees 09' W). N and P resorption proficiency were determined from senescing leaves in 11 dominant tree species. Nitrogen was analysed by microkjeldahl digestion with sulphuric acid and distilled with boric acid, and phosphorus was analysed by digestion with nitric acid and perchloric acid. Soil was rich in total N (0.50%, n = 30) and extractable P (4.11 microg g(-1) n = 30). As expected, trees showed incomplete N (1.13%, n = 11) and P (0.11%, n = 1) resorption. With a more accurate method of nutrient resorption assessment, it is possible to prove that a forest community with a nutrient-rich soil can have low levels of N and P resorption. PMID- 17354447 TI - Effect of 2,4-d, hydric stress and light on indica rice (Oryza sativa) somatic embryogenesis. AB - With the purpose of increasing the embryogenesis regeneration process in vitroplants obtained from somatic embryos of the indica rice variety CR-5272 (Oryza sativa L.), two independent experiments were performed. The first experiment consisted in the effect of combination of three concentrations of the gelling agent Phytagel (1.8. 2.4. and 3 gL(-1)) and four 2,4-D concentrations (2.26, 4.52. 6.78, and 9.05 microM) on the induction and subsequent regeneration of embryogenic calli. On the second experiment, the pre-regeneration phase was modified: calli were subjected to darkness or diffuse light conditions for one, two, and three weeks. In embryogenesis induction, 35% calligenesis was obtained using the MS culture medium supplemented with 6.78 microM of 2.4-D and 2.4 gL(-1) Phytagel, whereas on the control treatment (MS medium supplemented with 9.05 microM of 2.4-D and 3 gL(-1) Phytagel ) 24% calligenesis was obtained. In addition, regeneration percentages were improved (22% and 16% for calli induced with the above treatments, respectively). Furthermore, in light exposure experiments, the best result was obtained by exposing the embryogenic calli to darkness for one week in pre-regeneration, followed by direct light exposure during the regeneration phase. PMID- 17354448 TI - Density-dependent reproductive and vegetative allocation in the aquatic plant Pistia stratiotes (Araceae). AB - Pistia stratiotes is an aquatic macrophyte that grows in temporary-ponds in the southern Pantanal, Brazil. It reproduces both sexually and asexually and is usually observed forming dense mats on the water surface, a condition favored by the plant's vegetative reproduction coupled with an ability for rapid growth. In this study we examined the effect of densely crowded conditions on the production of reproductive and vegetative structures. In addition, we verified whether there is a trade-off between clonal growth and investment in sexual reproductive structures, and whether there is an allocation pattern with plant size. Individual plant biomass and the number of the rosettes producing sexual reproductive structures and vegetative growth structures both increased with density. Increase in plant size resulted in increased proportional allocation to sexual reproductive structures and vegetative growth structures. Allocation of biomass to reproduction did not occur at the expense of clonal growth. Thus, the density response appears as a increase of rosettes producing sexual reproductive structures and vegetative growth structures. Therefore, long leaves and stolons may be adaptive under densely crowded conditions where competition for light is intense. An important aspect in the study of trade-offs is the size-dependency of the allocation patterns .Usually, larger plants produce more biomass. Therefore, larger plants can allocate more biomass to both vegetative and sexual reproduction than smaller plants and thus show a positive correlation between both traits rather than the expected negative one. PMID- 17354449 TI - Heterogeneity of terrestrial bromeliad colonies and regeneration of Acacia praecox (Fabaceae) in a humid-subtropical-Chaco forest, Argentina. AB - In several tropical and subtropical forests, plants of the understorey act as an ecological filter that differentially affects woody species regeneration. In convex sectors of the Schinopsis balansae (Anacardiaceae) forests of the Southeastern Chaco there are dense colonies of terrestrial bromeliads. These may influence forest regeneration by intercepting rain water and propagules in their tanks. Within colonies, the spatial distribution of bromeliads is clumped because their clonal growth leaves numerous internal gaps. In this study we describe the internal heterogeneity of three bromeliad colonies (plots) and analyze how this heterogeneity affects Acacia praecox regeneration (i.e. seedling recruitment and survival). In January 1996, we randomly placed three transects with 150 contiguous quadrats of 100 cm(2) in each plot. For each quadrat we recorded the type of floor cover (i.e. bromeliads, herbs, litter, or bare soil) and the presence of A. praecox seeds or seedlings. In July 1996 we relocated the transects and recorded seedling survival. Bromeliad colonies showed a high internal heterogeneity. Almost half of the 450 quadrats were covered by two terrestrial bromeliads. Aechmea distichantha was recorded in 81% of all quadrats with bromeliads, and Bromelia serra in the others. All quadrats with bromeliads were covered by litter. Half of them were occupied by the bases of bromeliads and the others were covered by their leaves. In contrast, where bromeliads were not present, soil surface was covered by litter in 83% and by herbaceous vegetation in 11% of the quadrats; very few quadrats were covered by bare soil. In January 1996, we recorded 127 seeds and 176 seedlings of A. praecox. Seed and seedling densities of A. praecox were similar in quadrats with and without bromeliads, but variability in seedling density of A. praecox was higher within than among plots. Seed density was higher in quadrats covered by bromeliad leaves than inside the tanks. Seedling survival of A. praecox was slightly higher in quadrats with bromeliads in only one of the three plots. No seedling survived inside the bromeliad tanks. Apparently. bromeliad colonies have no effect on seedling regeneration of A. praecox. PMID- 17354450 TI - [Vegetation diversity, composition and structure in a cattle agro-landscape of Matiguas, Nicaragua]. AB - The diversity, composition and structure of vegetation in a cattle landscape in Matiguas, Nicaragua was characterized, and the floristic and structural differences of six types of habitats (secondary forests, riparian forests, charrales, live fences and pastures with high and low tree cover) were compared. A total of 3 949 trees of 180 species and 52 families were recorded. Forty six percent of the total trees reported for the landscape were represented by Guazuma ulmifolia (18.5%), Bursera simaruha (13.2%), Tabebuia rosea (6.3%), Enterolobium cyclocarpum (4.2%) and Albizia saman (3.4%). Many of the dominant species in the landscape were typical of open and disturbed areas. There were significant differences between the different habitats in the patterns of tree species richness, abundance, diversity, structure and floristic composition. The riparian forests had greater tree richness (p=0.0001) and diversity (p=0.0009) than other habitats. The floristic composition varied across habitats. with pairs of habitats sharing between 18.4 and 51.6% of the same tree species, and with clear differences in composition between the forested (riparian and secondary forests) and agricultural habitats. Of the habitats studied, the riparian forests and secondary forests seem to have greatest value for the conservation of the flora in the agropaisaje because they have the greatest species richness, and maintain small populations of endangered species. On the basis of the study, we recommend including agricultural landscapes in strategies to conserve tree diversity and suggest measures to ensure the maintenance of tree diversity in the Matiguas landscape. PMID- 17354451 TI - [Breeding systems of the Paraguana coastal plain plants, Venezuela. ]. AB - Breeding systems were evaluated for 51 plant species according to life form, pollination system, vegetation type, and phenology, in the coastal plain of Paraguana Peninsula, Venezuela. Sexual systems were no associated to life form, pollination system, vegetation type, and phenology. The frequency distribution of sexual system was 82.3% hermaphroditism, 15.6% monoecy, and 1.9% dioecy. All sexual systems had a peak during the lowest rainfall. Genetic system distribution was 64.8% self-compatibility (including partially self-compatibility) and 35.2% self-incompatibility. Among self-compatible species, 45.1% were autogamous (19.6% not autogamous). The genetic systems were associated significantly to: (1) plant life form: self-compatible species tend to be herbaceous and self-incompatible plants tend to be woody species; (2) vegetation type: self-compatible species were predominant in the three vegetation types, but in the mangrove the frequency of self-compatible and self-incompatibles was similar; and (3) pollination system: most of the self-compatible species were polyphilous. Mating systems: xenogamous and autogamous species were associated only with plant life forms. Xenogamous plants were mostly woody species and autogamous plants were mostly herbaceous species. The high incidence of hermaphroditism, self-compatibility, and autogamy are related to herbaceous life form, polyphilous pollination system, and climatic conditions, together the insularity of the Paraguana peninsula. PMID- 17354452 TI - Essential oil of trees of the genus Ocotea (Lauraceae) in Costa Rica. I. Ocotea brenesii. AB - The chemical composition of the essential oils from leaves and wood of Ocotea brenesii Standl. growing wild in Costa Rica was determined by capillary GC/FID and GC/MS. From the leaves, 64 compounds were identified, corresponding to 85.9% of the oil, and from the wood 57 compounds were identified corresponding to 69.0% of the oil. The major constituents identified in the leaf oil were alpha-copaene (21. 1%), 8-cadinene (9.2%), spathulenol (7.3%), globulol (5.6%) and beta caryophyllene (5.2%). The major constituents of the wood oil were alpha-copaene (6.6%), caryophyllene oxide (6.3%). beta-caryophyllene (6.1%) and humulene epoxide (4.6%). PMID- 17354453 TI - [Intestinal parasites in howler monkeys Alouatta palliata (Primates: Cebidae) of Costa Rica]. AB - Fecal samples of 102 howler monkeys (Alouatta palliata) from several sites of Costa Rica were studied for intestinal parasites. The zones studied were: Central Valley (San Ramon, Alajuela), Central Pacific (Chomes and Manuel Antonio National Park. Puntarenas), North Pacific (Palo Verde Park and Playa Potrero, Guanacaste). Chira Island in the Nicoya Gulf and Caribean area (Cahuita. Limon). Animals were anesthetized with dards containing Telazol in order to collect the fecal material; some monkeys defecated spontaneously and others by direct stimulation. Samples were studied in saline solution (0.85%) and a Iodine solution, or stained with Haematoxylin. The material was also cultured in Dobell culture medium to determine the presence of amoeba and flagellates. Strongvloides. Controrchis. Trypanoxyuris genera were found in 3.4% of the samples. In addition 16.7% to 80% of the animals showed protozoa infection with Endolimax, Entamoeba, Trichomonas and Giardia. It is discussed the relationships of parasite infection with environmental conditions, animal population and human presence, specially in the monkey conservation programs point of view. PMID- 17354454 TI - Biomass production and nutritional value of Artemia sp. (Anostraca: Artemiidae) in Campeche, Mexico. AB - Biomass of the crustacean Artemia sp. has multiple uses. The biochemical composition and biomass production of Artemia grown from cysts produced by a native population from Real de Salinas were evaluated under laboratory conditions. Nauplii (instar I) were stocked at density of 10 nauplii/ml in 1.5 l tanks, fed with rice bran from day 2 to day 6, and with the microalgae Tetraselmis suecica from day 7 to day 15. At the end of the trial (day 15) the average length was 5.34 mm, biomass production was 15.72 g/l (wet weight), and survival was 79%. The proximal analysis and biochemical composition of Artemia biomass indicated that its nutrient percentages are closely similar to Artemia from other regions, making this species a suitable food for cultured fish and crustacean. PMID- 17354455 TI - Contribution of food availability to the more rapid growth of the scallop, Euvola ziczac (Pteroida, Pectinidae) in bottom than in suspended culture. AB - We conducted a 5-month experiment at Turpialito in the Golfo de Cariaco, Venezuela, to examine whether the previously reported more rapid growth of scallop Euvola ziczac in bottom compared to suspended culture can be attributed to more abundant or higher quality food resources near the sediment/water interface. The various body components (shell, muscle, digestive gland, gonad and remaining tissues) increased in size at a much greater rate for scallops maintained on the bottom, in partly buried cages at 5 m in depth, than in cages suspended at the same depth in the water column. Furthermore, survival was greater on the bottom. Food abundance and quality were examined by analyzing the seston collected in sediment traps at the sediment/water interface in the vicinity of the bottom cages and next to the suspended cages. Phytoplankton abundance (chlorophyll a) and the proportion of various fatty acids in the lipid fraction of the seston were similar on the bottom and in suspension. However, sestonic protein, lipid and carbohydrate levels, and the estimated energetic content of the seston, were higher on the bottom than in suspension, and probably contributed to the greater growth on the bottom. As the increase in the energetic content of the seston on the bottom compared to in suspension was less than the increase in growth (biomass) on the bottom compared to in suspension, and the evidence showed in previous studies above the negative influence of fouling and wave action in suspended culture, we conclude that the more rapid growth of Euvola ziczac in bottom than suspended culture is principally due to stress relative to suspended culture system. PMID- 17354456 TI - [Fishery and biometrics of genus Calappa crabs (Brachyura: Calappidae) in northeastern Venezuela]. AB - The box crabs, genus Calappa, are important crab species landed by the industrial trawl fleet in Venezuela. These crabs have a wide distribution in the country, from the Gulf of Venezuela to the Orinoco River, but major landings take place in such gulf, near Margarita Island and northern Sucre State. Average annual landing in the eastern region was 69 t during 1970-2001, with a maximum of 221 t. For this study a sample of 2 398 box crabs was collected by observers on board of industrial trawl vessels, which operated in eastern Venezuela from 1994 to 2000. Three species were found in the landings, Calappa sulcata and C. flammea. each represented 47% of the sample, and C. nitida, which accounted for 5% of the sample. Sex ratio was strongly biased towards males in C. sulcata (2.8:1) and in C. flammnea (1.9:1). while it was only slightly biased in C. nitida (1.4:1). Due to its large size, C. sulcuta is of great commercial interest, with average weight 290 g and a maximum weight of 720 g: C. flammea showed an average weight of 140 g and a maximum weight of 418 g, while C. nitida is the smallest species, with average weight 46 g and maximum weight not beyond 113 g. Box crabs were captured by day and night in similar proportions, and were found in a wide depth range, from a few meters to 126 m deep; however, the largest captures were obtained in the interval 38 - 54 m. Regressions between weight of chelae and total weight were linear, and significantly different between sexes. The relation between total weight and carapace width was allometric, with a power exponent ca. three in C. sulcata, and less than three in C. flamea and C. nitida. Females of C. sulcata and C. nitida showed power exponents significantly smaller than males. Since claws are removed from the animal to be commercialized, while the rest of the animal is returned alive to the sea, for practical purposes a common equation among species and sexes to convert claws weight into total body weight is: total weight - 3 x claws weight. The relationship between catch per unit of effort (CPUE) and effort did not show a significantly decreasing trend, but landings follow the effort trend, with a decreasing tendency in recent years. No mature females were found in any of the three species, thus there could be reproductive migrations towards deeper waters from October to January, when abundance of crabs is lower in the study area. It is recommended that the practice of exploiting only one claw, returning the rest of the animal alive to the sea, should be promoted among fishers, while the removal of claws from female crabs should be avoided. PMID- 17354457 TI - Decadal variability in growth of the Caribbean spiny lobster Panulirus argus (Decapoda: Paniluridae) in Cuban waters. AB - Annual von Bertalanffy growth parameters of the Caribbean spiny lobster (Panulirus argus) in Cuban waters were estimated from a long term study (40 years) by length-based methods ELEFAN and the new version of SLCA. Data of around 800 000 lobsters (with carapace length ranging 14 to 199mm) were randomly sampled in artificial shelters (a non selective fishing gear very common in the lobster fishery), through the field monitory program established for this species since 1963 in 14 localities of southwestern Cuban shelf. The software ELEFAN showed problems to converge in an optimal combination of the instantaneous growth coefficient (K) and the asymptotic length (Linfinity) of the von Bertalanffy equation, whereas the new SLCA software produced value estimates of K between 0.20 and 0.27 year(-1) and values of Linfinity between 177 and 190 mm carapace length, all within the range reported in the literature. The standardized anomalies of both parameters showed the presence of cycles along the analyzed time series. Decadal variability in growth parameters was revealed through the spectral analysis indicating cycles of 16 and 20 years for K and of 16 years for Linfinity. The incidence of some factors such as biomass and temperature that modulate growth in this crustacean was explored, using a nonlinear multiple regression model. These combined factors explained 33% and 69% of the variability of K and Linfinity respectively. The growth coefficient appeared to be maximum with annual mean sea surface temperature of 28. 1 degrees C and the largest Linfinity is reached at a annual men biomass level of 23,000 t. These results should be the basis to understand the Cuban lobster population dynamics. PMID- 17354458 TI - Life history and systematics of Albusambia elaphoglossumae (Lepidoptera: Crambidae): a new genus and species of musotimine with leaf-mining biology from Costa Rica. AB - Albusambia elaphoglossumae Solis & Davis, a new genus and species, is described. It was discovered mining the fronds of the fern Elaphoglossum conspersum in Costa Rica (San Jose and Cartago Provinces, at elevations of 2300-3100 m). The type series was obtained by rearing of the immature stages in laboratory. The adult is defined by unique genital characters, and the pupa with a medial depression on the vertex and with two anterolateral horn-like structures on the prothorax. The larva is a gregarious leaf miner with its body flattened dorsoventrally and head prognathous; morphological adaptations to its leaf-mining habit are new to the Musotiminae. Fern-feeding musotimines are important to the discovery of new biological control agents for invasive ferns. PMID- 17354459 TI - [Development of the tropical fish Xenomelaniris brasiliensis (Pisces: Atherinidae) from embryo to larva and time to metamorphosis]. AB - Embryonic-larval development, and metamorphosis larval time, were studied in the tropical fish Xenomelaniris brasiliensis. Twenty nine sexually mature specimens were used, 16 females (10.86+/-1.01 cm and 7.63+/-2.62 g) and 13 males (10.43+/ 0.57 cm and 6.54+/-1.44 g) which produced gametes through abdominal massage. Fertilized eggs were spherical (1.18 +/-0.44 mm diameter), greenish, transparent, benthonic and vitelus-rich; rugose striated chorion with numerous external filaments randomly distributed and abundant oil globules (0.11 + 0.07 mm diameter). The embryonic development was finished at 26.36+/-2.03 degrees C, 39.67+/-0.58 PSU and pH 8.30+/-0.10. Larvae (4.56+/-0.97 mm total length) hatched at 143 hours and 19 minutes. with vitteline sac vestiges and a single oil globule. The larvae were fed on Brachionus plicatilis and Isochrysis galbana. After the second week .4rtemia nauplii were added and I. galbana maintained. Flexion started 13 days after larvae hatched (6.10+/-1.54 mm total length) and was completed 32 days later (11.25+/-1.87 mm total length) with the hipural complex completely developed. In conclusion, X brasiliensis showed direct larval development and started larval metamorphosis (13.08+/-2.07 mm total length) to juvenile 40 days after hatching. PMID- 17354460 TI - Reproductive biology of Oreochromis niloticus (Perciformes: Cichlidae) at Emiliano Zapata dam, Morelos, Mexico. AB - The reproductive season of tilapia was studied by monthly samplings at Emiliano Zapata dam, Morelos State, Mexico. From February 1999 through February 2000 a sample of 50 fish was taken from the commercial catch (castnet, 6.5 cm of mesh size). The observed sex ratio was 1:1.29 (females:males) (chi(2)=10.26; p<0.05). The tilapia reached maturity at 151.3 mm (females) and 152.0 mm (males) of total length. Rainy (August) and dry (February) seasons were determined as the breeding period. Fecundity variation was better correlated with length (r=0.7473: p<0.002) than with weight (r=0.7395; p<0.002). The fecundity ranged between 243 and 847 oocytes per fish, with egg diameter from 300 to 3 700 microm. Intensive breeding activity in August and February coincide with phytoplankton biomass increase. PMID- 17354461 TI - [Structure of reef fish communities in Catalinas Islands and Ocotal beach, North Pacific of Costa Rica]. AB - The reefs are heterogeneous systems that maintain a high diversity of organisms. Fish community structure varies within and among reefs, so it would be expected that reef structure and heterogeneity should affect fish communities inhabiting reefs. Four reef patches at Catalinas Islands (Sur, La Pared, Roca Sucia and Sombrero) and one in Ocotal beach (10 degrees 28'45" N; 85 degrees 52'35" W) were studied with visual censuses (July-December 2003). The structure and composition of fishes between Catalinas islands and Ocotal beach were different, and habitat structure and composition explain most of the variance founded. The presence of the fleshy algae Caulerpa sertularioides in Ocotal, and the corals Tubastrea coccinea and Pocillopora spp. at Catalinas Island explained the variability among sites and how it affected fish community structure and composition. The butterfly fish Johnrandallia nigrirostris, damselfish Microspathodon dorsalis, and surgeon fish Prionurus punctatus were directly correlated with the ahermatipic coral Tubastrea coccinea in Roca Sucia reef, while the angel fish Holacanthus passer was associated to reefs with a major percentage of rocky substrate. Other species such as the damselfish Abudefduf troschelli and Halichoeres dispilus were more abundant at Ocotal, where the algae C sertularioides dominated. The number and abundance of reef fishes was directly correlated with the rugosity index at the reefs of Roca Sucia and Ocotal, but not at reefs of La Pared and Sombrero. PMID- 17354462 TI - [A new Ecuadorian species of the Andean fish genus Grundulus (Characiformes: Characidae)]. AB - The new species Grundulus quitoensis is described from El Voladero Lake, El Angel Biological Reserve, Northern Ecuador. The new taxon can be distinguished from all congeners by the following characters, respectively: a low number of unbranched rays in the anal fin (three vs. four-five) and in pectoral fins (on vs. two - three), a higher number of dentary teeth (12-14 vs. 8-10), a second infraorbital about three times larger than the first (vs. about two times larger), a third infraorbital which is not in contact with the preopercle (vs. in contact with preopercle), the presence of four small fenestrae in the infero-lateral bone dentary (vs. one - two); and a premaxilla which presents a long lateral process (vs. short), a maxilla with two notches in the infero-lateral surface (vs. one notch in the infero-lateral surface). PMID- 17354463 TI - Blood and urine physiological values in farm-cultured Rana catesbeiana (Anura: Ranidae) in Argentina. AB - A total of 302 samples of healthy farm-cultured Rana catesbeiana specimens (9-21 months-old, 50-350 g liveweight, 50% each sex) from the north-east of Argentina, were analyzed through spectrophotometry, electrophoresis, densitometry, refractometry and microscopy in order to obtain blood and urine normal values. Confidence intervals (p<0.05) for PCV (28.6-31.6%), RBC (0.40-0.44 T/L), MCV (686 732 fL), hemoglobin (6.41-7.20 g/dL), MCH (151-164 pg), MCHC (22.6-24.0%), WBC (18.7-22.3 G/L), neutrophils (58.4-63.4%), lymphocytes (23.9-29.8%), monocytes (2.1-3.8%), eosinophils (4.6-7.0%), basophils (2.9-4.1%), bleeding time (289 393s), coagulation time (452-696s), prothrombin time (76-128s), urinary density (1.0061-1.0089 g/mL), urinary pH (6,38-6.96)., fibrinogen (0.59-0.99 g/dL), total protein (4.19-4.49 g/dL), albumin (1.49-1.67 g/dL), alpha-1 globulin (0.20-0.24 g/dL), alpha-2 globulin (0.48-0.54 g/dL), beta globulin (0.68-0.77 g/dL), gamma globulin (1.28-1.42 g/dL), albumin/globulin ratio (0.50-0.58), creatinine (4.09 5.56 mg/L). urea (76.1-92.4 mg/L), uric acid (11.5-15.4 mg/L), triglycerides (0.34-0.52 g/L), total cholesterol (0.56-0.67 g/L), HDL-C (0.03-0.05 g/L), LDL-C (0.34-0.44 g/L), alpha lipoprotein (6.01-8.67%). beta lipoprotein (91.3-93.9%), glucose (0.45-0.54 g/L), Na (116-121 meq/L), K (3.42-3.81 meq/L), Cl (100-116 meq/L), Ca (7.98-8.61 mg/dL). P (8.319.36 mg/dL), Mg (2.26-2.55 mg/dL), Fe (105 178 ug/dL), ALP (144-170 [U/L), ALT (10.0-14.8 IU/L), AST (42.8-53.4 IU/L), GGT (7.8-10.6 IU/L), LDH (99-135 IU/L), CHE (151-185 lU/L) and CPK (365-500 IU/L), were obtained. Some parameter ranges were similar to those obtained in amphibians, birds or mammals; others were very different. These parameters are useful to evaluate sanitary, metabolic and nutritional state on captive bullfrogs. PMID- 17354464 TI - The tadpoles of Hyla rufitela (Anura: Hylidae). AB - The validity of the published description of Hyla rufitela is questioned because the origin of the described tadpoles does not correspond to the distribution of this species. The present description, based on tadpoles that were hatched from two egg masses from the Caribbean lowland of Costa Rica, includes tadpoles raised to adult frogs to verify the species. The newly described tadpoles differ from the previously described and illustrated ones not only in color but also by its more slender body shape (body height:body length, 0.43:0.47). the more slender tail (%, tail length of total length, 69%:63%). the more conspicuous spiracle and its position, as well as by the larger oral disk width (oral disk width:body width, 0.44:-0.33). The young tadpoles continually ingest mud as is typical of bottom feeders. Nevertheless. older larvae feed on plant material like rotting mellow leaves of Piper auritum. The tadpoles metamorphosed between 44 and 114 days (x=80.3 days) under the described breeding conditions. PMID- 17354465 TI - [Anuran fauna from Salta city, Argentina]. AB - The loss and transformation of habitat by anthropogenic activities is one of the main causes of biodiversity decrease. Amphibians are declining all over the world and one of the causes of this decline is thought to be habitat reduction. However, there are anuran populations in highly disturbed habitats, like cities. This study presents the ecological baseline needed to understand anuran communities in urban environments, for Salta City. Argentina (ca. 502,000 inhabitants). The sample was stratified by environments defined by infrastructure and geographic location. The species were identified by visual encounter techniques and by auditory transect during the 2002-2003 reproductive period. Three families, seven genera and twelve species were recorded and the species richness decreased from city border to center. Similarity index values among geographic areas was higher East-West (94.7) than South-West (33.3). Bufo arenarum was the only species recorded in all environments. Hyla andina and Odontophrynus americanus had a restricted distribution and are here considered vulnerable. The border effect can explain some distribution pattern in these populations. A map of the potential distribution of recorded species for Salta is provided. PMID- 17354466 TI - Birds of a high-altitude cloud forest in Alta Verapaz, Guatemala. AB - The Northern Central American Highlands have been recognized as endemic bird area, but little is known about bird communities in Guatemalan cloud forests. From 1997 to 2001 a total of 142 bird species were recorded between 2000 and 2400 masl in cloud forest and agricultural clearings on Montana Caquipec (Alta Verapaz, Guatemala). The bird community is described based on line transect counts within the forest. Pooling census data from undisturbed and disturbed forest, the Gray-breasted Wood-Wren (Henicorhina leucophrys) was found to be the most abundant species, followed in descending order by the Common Bush-Tanager (Chlorospingus ophthalmicus), the Paltry Tyrannulet (Zimmerius vilissimus), the Yellowish Flycatcher (Empidonax flavescens), the Ruddy-capped Nightingale-Thrush (Catharus frantzi), and the Amethyst-throated Hummingbird (Lampornis amethystinus). Bird communities in undisturbed and disturbed forest were found to be similar (Serensen similarity index 0.85), indicating low human impact. Of all recorded species, approximately 27% were Nearctic-Neotropical migratory birds. The most abundant one was the Wilson's Warbler (Wilsonia pusilla). The Montana Caquipec is an important area for bird conservation, which is indicated by the presence of four species listed in the IUCN Red List (Highland Guan Penelopina nigra, Resplendent Quetzal Pharomachrus mocinno, Pink-headed Warbler Ergaticus versicolor, Golden-cheeked Warbler Dendroica chrysoparia), and 42 Mesoamerican endemics, of which 14 species are endemic to the Central American Highlands. The results presented here will be useful as baseline data for a long-term monitoring. PMID- 17354467 TI - Sighting frequency and relative abundance of bottlenose dolphins (Tursiops truncatus) along the northeast coast of Margarita Island and Los Frailes Archipelago, Venezuela. AB - The study of local cetaceans in Venezuela has a very recent history, and few efforts have been made in the assessment of coastal populations based on field research. The occurrence of whales and dolphins along the northeast coast of Venezuela has been documented through sightings and stranding records. Given the underwater topographical features and the influence of upwelling processes, this area is considered a very productive coastal ecosystem. Our objective was to establish the sighting frequency and relative abundance of bottlenose dolphins in the area. Sighting records were gathered on bottlenose dolphins and other cetacean species occurring along the northeast coast of Margarita Island and Los Frailes Archipelago through direct observation during land-based (6 surveys, 48 hours of observation) and boat-based surveys (24 surveys, 121 hours of observation, 1295 km covered). A sighting frequency was calculated using two methodologies and then compared, considering: 1) a mean effective observation time (4.27 hours), and 2) distance covered with cetacean sightings (1108 kin). A third method is proposed relating a mean effective distance covered with cetacean sightings and expressed as a percentage. The abundance index was calculated using the mean effective observation time. The sighting frequency of Tursiops truncattus in the study area was 3 - 4 sightings per day of 4.27 observation hours, or by 185 kilometers covered. The relative abundance was calculated as 35 dolphins in the study area, so a total population of less than 60 dolphins could inhabit the proposed range. Tursiops truncatus is the dominant species in the northeast coast of Margarita Island and Los Frailes Archipelago with 70% of all the sightings, so this locality could be termed as the distribution range of a possible local population of bottlenose dolphins. PMID- 17354468 TI - Azelaic acid gel 15%: clinical versatility in the treatment of rosacea. AB - There are numerous proposed but contested components involved in the pathophysiology of rosacea, including inflammatory mediators, reactive oxygen species (ROS) released by neutrophils, and microbial components. Ideal comprehensive rosacea management should address these components. Azelaic acid (AzA), a naturally occurring substance, has many proposed mechanisms of action- antimicrobial, anti-inflammatory/antioxidant, and keratinolytic--that address the proposed components of rosacea pathophysiology and has demonstrated efficacy in subtype 2 rosacea. In a roundtable discussion, information leaders discussed the pathophysiology of rosacea and other issues of importance to successful rosacea management, such as skin care regimens, quality of life (QOL), and compliance. PMID- 17354469 TI - [Hemolytic uremic syndrome (HUS). An up-dated nosological classification]. AB - An up-date of the causes and pathogenesis of the HUS is reported. After more than 40 years of research we are able to define the infectious agents and the toxin involved. The mechanisms and the molecules involved in the non-diarrheal (atypical) entities producing HUS have also been characterized. This new situation allows us to develop a diagnostic algorithm that enables us to better define preventive and therapeutic measures, based on more rational evidence. PMID- 17354470 TI - [Hemolytic uremic syndrome. Clinical manifestations. Treatment]. AB - Clinical manifestation are described in children with epidemic HUS. The intestinal involvement in the prodromic period, is outlined and the most common disturbances such acute renal failure, thrombocytopenia, hemolytic anemia, leucocitosis hypertension, neurological, pancreatic and cardiac manifestations are described. We discuss the acid-base and electrolyte disturbances, metabolic acidosis, hyponatremia, hyperkalemia. The etiopathogenic treatment and the control of renal sequelae are also discussed. PMID- 17354471 TI - [Role of the Shiga toxin in the hemolytic uremic syndrome]. AB - In the last years, infection associated with Shiga toxin-producing Escherichia coli (STEC) and subsequent Hemolitic-Uremic Syndrome (HUS) became relevant as a public health since it was considered as one of the most important emergent patogen present in the food contaminated by cattle feces. STEC infection may be asymptomatic or begins with a watery diarrhea that may or may not progress to bloody diarrhea (hemorrhagic colitis) and HUS. In Argentina, HUS is the most common pediatric cause of acute renal insufficiency and the second cause of chronic renal failure. Up to now, STEC infection lacks of known effective treatment strategies that diminish risk of progression to HUS. The mechanisms by which Shiga toxin (Stx) induce HUS may help to find strategies to prevent or ameliorate HUS. In this article, recent progress that has contributed to understanding the disease pathogenesis of STEC is reviewed. New strategies to prevent further uptake of Shiga from the gut, either during the diarrheal phase or once HUS has developed are discussed. PMID- 17354472 TI - [Activation of innate and specific immune responses in hemolytic uremic syndrome (HUS)-patients]. AB - The central role of the immune system is the preservation of the health against several pathogenic microbes and injury agents. However, on special conditions defensive mechanisms triggered towards the foreign agent can damage the host. Clinical and experimental evidence indicate that inflammatory reaction triggered by the main components of Shiga toxin (Stx)-producing Escherichia coil (STEC), participate in the evolution to the complete form of HUS. When children are diagnosed of HUS, they present evidence that have suffered a very strong and early inflammatory response. These features include: the presence of a marked neutrophilia, the polymorfonuclear leucocytes (PMN) are "deactivated or exhausted" and the monocytes are differentiated towards an inflammatory phenotype (CD14-reduced and CD16-enhanced membrane expression). In addition, HUS-patients show a marked reduction in the absolute and relative number of leucocytes carrying the receptor (CX3CR1) for the chemokine "Fractalkine" (FKN, CX3CL1), which are the classic monocytes and Natural Killer cells (NK). All these cells express a high cytotoxic potencial. The chemokine FKN is expressed in endothelial and epithelial renal cells, and is involved in the pathogenic mechanism of different nephropathies. Noteworthy, we found a significant correlation between the severity of the renal damage (as days of anuria) and the alterations described above. Finally, the protective role of specific immune response, mainly through the antibody production with Stx-neutralizing capacity, is discussed. PMID- 17354473 TI - [Hemolytic uremic syndrome (HUS): medical and social costs of treatment]. AB - Hemolytic Uremic Syndrome (HUS) is the most frequent cause of renal failure in children, and the second cause of renal transplant. Argentina has the highest incidence of the world. Direct and indirect costs of HUS in its different clinical phases were studied. A retrospective review of all clinical notes of patients attending the hospital during the period 1987-2003 was carried out. Cost of every medical intervention, including diagnostic and therapeutic actions were calculated by the Hospital Department of Costs, according to two criteria: cost per process and cost per patient (considering total processes received each). Indirect costs were estimated according to guidelines established by the National Institute of Statistics and Census (INDEC): 1) family costs 2) social expenses afforded by the state, 3) cost of health services. Out of a total sample size of 525 patients, 231 clinical notes of children were selected and studied. The direct cost per patient in the acute period was US dollar 1 500, the total direct cost of care for each patient per year was US dollar 15 399,53; indirect costs per patient and for all year were US dollar 3 004,33 and US dollar 7 354,98 respectively. Total costs during 2005 per patient and per year was US dollar 17 553,39 and US dollar 2 170 477,37 respectively. Our study provides valuable information not only for purposes of health care planning, but also for helping authorities to set priorities in health, and to support the idea of developing preventive actions in a totally preventable condition in Argentina. PMID- 17354474 TI - [The epidemiology of hemolytic uremic syndrome in Argentina. Diagnosis of the etiologic agent, reservoirs and routes of transmission]. AB - Shiga toxin-producing Escherichia coli (STEC) cause sporadic cases and outbreaks of nonbloody and bloody diarrhea, and hemolytic uremic syndrome (HUS). E. coil O157:H7 is the most prevalent STEC serotype. However, other serotypes (O26:H11; O103:H2; O111:NM; O121:H19; O145:NM, among others) can cause a similar disease spectrum. Shiga toxins (Stx1, Stx2, and their variants), intimin, and enterohemolysin are the main virulence factors. Three different diagnostic criteria are used to determine the frequency of STEC infection: 1) isolation and characterization of STEC strains; 2) detection of specifically neutralizable free fecal Stx; and 3) Serological tests to detect Stx-antibodies. The surveillance of the STEC strains is performed using subtyping techniques: a) genotyping of Stx and eae by PCR-RFLP; b) phage typing of E. coil O157 strains; and c) pulsed-field gel electrophoresis. STEC O157 and non-O157 strains are recovered from clinic, animal, food and environmental samples, and E. coli O157:H7, a Stx2 and Stx2c producer, harboring eae and ehxA genes, is the most common serotype. During a prospective case-control study conducted to evaluate risk factors for sporadic STEC infection in Mendoza Province and Buenos Aires City and its surroundings during 2001-2002, exposures associated with risk included eating undercooked beef, contact with a child < 5 years with diarrhea and living in or visiting a place with farm animals. Both washing hands after handling raw beef, and eating fruits and vegetables were frequently protective. Strategies of prevention and control are necessary to decrease the incidence of STEC infections in Argentina. PMID- 17354475 TI - [Control of enterohemorrhagic Escherichia coli (EHEC) in cattle]. AB - Cattle are recognized as the major reservoir of STEC and the source of infection for human beings. Until recently, intervention strategies to decrease the contamination of meat products have been focused on the slaughter plant with the application of practices to reduce the contamination and proliferation of STEC. This has now changed following the development of intervention strategies in the farm. This could be one of the most important points of intervention to lower the incidence of human infection. Vaccines, probiotics, bacteriophages, and changes in production practices may be useful as strategies to control EHEC in the cattle. The application of such intervention measures could be difficult due to the fact that this zoonotic agent rarely causes disease in bovines. The HUS is endemic in Argentina, and the factors leading to this epidemiological situation remain unknown. However, intervention strategies undoubtedly will contribute to reduce the incidence of this zoonosis. PMID- 17354476 TI - [Epidemiological role of pets in urban transmission cycle of STEC]. AB - Escherichia coli is an important constitutional element of both animal's and men's microbiote. Rumiants in general and bovine in particular have been pointed out as reservoirs of shigatoxigenic (STEC) and enterohemorragic strains (EHEC). These strains are rarely reported in pets isolations and are badly documented. Revisions of the pathogenic role of E. coli in small animals, particulary based on intestinal and urogenital isolations, involve in a very low proportion the STEC strains. In dogs, ocasional isolations are reported, from feces coming from both healthy and diarreic dogs. The STEC intestinal strains prevalence in dogs and cats from urban centers, based on the habit of including regular or ocasional raw meat in their diet, should not be understimated. PMID- 17354477 TI - [Education for consumers: one of the tools for decreasing the incidence of hemolitic uremic syndrome]. AB - In order to guarantee that harmless food is ingested by consumers, it is essential that strict hygienic procedures are followed both during the elaboration of food and during the procedures that range from the purchasing, the cooking and the consumption of food. This is an invaluable and unquestionable tool that should be used in order to decrease the incidence of Hemolytic Uremic Syndrome (HUS) in our country. The State, the enterprise owners, and the consumers should take responsibility for this: the State should guarantee the citizens' access to safe food products through an adequate legislation and a mechanism for it to be controlled and obeyed; the enterprise owners should obey the current regulations and provide their employees with education about the importance of these regulations; and the consumers should take responsibility for how they handle food. PMID- 17354478 TI - [Life-experience workshops with hemolytic uremic syndrome patients relatives. Towards an integral approach for HUS treatment]. AB - This article describes a group technique designed to assist (affective and contention needs from) relatives of children who have suffered HUS. It consists on group meetings, called Life-Experience Workshops, where central topics considered important by the participants are discussed. These group meetings with HUS patient's relatives have no reported precedents and permit analyzing the traumatic value of life-experiences during and after the disease acute phase and its impact on the family involved. As a conclusion, it is considered that this first step opens possibilities to continue working and searching in this field, unexplored so far. A contribution to an integral approach for the child and his or her family is pursued, which complements medical treatment with a psychological and social perspective. PMID- 17354479 TI - The Columbia disaster, from a risk manager's view. PMID- 17354480 TI - Malpractice insurance: riding out the storm. PMID- 17354481 TI - Black & white guidance for a gray process. PMID- 17354482 TI - Rush Model can allow risk managers to control litigation costs. PMID- 17354483 TI - Vicarious liability. South Carolina hospital has non-delegable duty to provide competent care in ED. Simmons v. Tuomey Regional Medical Center, 533 S.E. 2d 312 (S.C. 2000). PMID- 17354484 TI - Products liability. Hospital in Missouri strictly liable for providing defective product to patient. Mulligan v. Truman Medical Center, _S.W. 2nd_, No. WD 52265 (Ct. App. Mo. July 8, 1997). PMID- 17354485 TI - Negligent credentialing. Claim not covered by general liability policies in Ohio. United States Fidelity and Guaranty Company v. St. Elizabeth Medical Center, 129 Ohio App. 3d 45, 716 N.E. 2d 1201 (Ct. App. Ohio 1998). PMID- 17354486 TI - Professional corporations. Professional corporation liable for malpractice of shareholders in Colorado. Peditatric Neurosurgery, P.C. v. Russell, 44 P. 3d 1063 (Colo. 2002). PMID- 17354487 TI - Masculinity in the twenty-first century: an introduction. PMID- 17354488 TI - On men crying: Lear's agony. AB - King Lear vowed that because he was a man he would rather go mad or die than weep. Many adult male patients in psychoanalysis have just such an internal prohibition against crying, learned individually and often culturally encouraged, a prohibition that affects their ability to process loss, maintain intimacy, and accept vulnerability. It is suggested that the appropriate psychoanalytic role with these patients is to recognize and actively address this culturally supported prohibition. In addition, it is proposed that the prohibition against men crying may be a consequence of male envy of maternal traits and other feminine characteristics. Further, it is suggested that the developmental theory that the male child must "disidentify" with the mother memorializes a phallicism that often invokes the prohibition against crying in men and is itself mistaken. PMID- 17354489 TI - Masculinity unraveled: the roots of male gender identity and the shifting of male ego ideals throughout life. AB - A model of masculine gender identity development is presented that demonstrates how a male's sense of his masculinity and the ambiguities of his gender are being reworked throughout his life. Of factors shaping the boy's sense of masculinity early on, particular emphasis is placed on the role of the involved father, the nature of the parental relationship, and the mother's recognition and affirmation of her son's maleness. While healthy masculine gender identity is founded predominantly on the boy's unique struggles in separating from his mother, it does not result from what has been traditionally viewed as the boy's disidentification from her (and from the feminine more generally). Indeed, boys who need to violently repudiate their identifications with their mother are more susceptible to a fragile, rigid masculine identity and narcissistic psychopathology. A case example of a young adult man illustrates the impact of identifications with both parents. The interplay of early masculine identity development and later life challenges confronting the adult male is briefly noted. "Masculine" ego ideals shift across developmental junctions until, ultimately, a more mature sense of masculinity emerges: the phallic wish to deny differentiation and maintain unlimited possibility is renounced and mourned and certain real limits concerning sex, gender, and generational differences are accepted. This reshaping of the "masculine" ego ideal consequently involves the transformation of a man's previously adaptive "phallicism" into more realistic, "genital" ego ideals-an achievement involving interplay between masculine and feminine identifications and the integration of antithetical elements no longer so unconsciously gendered. PMID- 17354490 TI - Masculinity and its discontents: commentary on Reichbart and Diamond. PMID- 17354491 TI - Riddles of masculinity: gender, bisexuality, and thirdness. AB - Clinical examples are used to illuminate several riddles of masculinity ambiguities, enigmas, and paradoxes in relation to gender, bisexuality, and thirdness-frequently seen in male patients. Basic psychoanalytic assumptions about male psychology are examined in the light of advances in female psychology, using ideas from feminist and gender studies as well as important and now widely accepted trends in contemporary psychoanalytic theory. By reexamining basic assumptions about heterosexual men, as has been done with ideas concerning women and homosexual men, complexity and nuance come to the fore to aid the clinician in treating the complex characterological pictures seen in men today. In a context of rapid historical and theoretical change, the use of persistent gender stereotypes and unnecessarily limiting theoretical formulations, though often unintended, may mask subtle countertransference and theoretical blind spots, and limit optimal clinical effectiveness. PMID- 17354492 TI - Masculinities, plural. AB - Masculinity cannot be regarded as a single entity. Both within Western culture and across cultures, a wide variety of masculinities are easily observable. Yet masculinity is so often contrasted with femininity that the many differences among men are at times obscured. To in part correct this deficiency, various "psychologies" of men are explored, as well as the cultural components that shape a society's ideas of what constitutes masculinity. Male heterosexuality and homosexuality are also examined, as are a number of the fantasies and fears that men typically experience. What cannot be left out of any exploration of male psychology are those sources of strength that permit so many men to fiercely protect their families and, when called upon, to fight their country's wars. Nonetheless, the differences between individual men are significant and can even be said to be vast. PMID- 17354493 TI - Masculinity as masquerade. PMID- 17354494 TI - The riddle of masculinity. Panel report. PMID- 17354495 TI - The threat of male-to-female erotic transference. AB - Vignettes from an ongoing psychoanalysis with a patient, Michael, are presented to illustrate the various dimensions of the erotic transference at different phases of the treatment. The relation to power, the experience and expression of aggression, how these may be organized by gender, and the female analyst's countertransference are discussed as potentially fostering or inhibitory in the development of an erotic transference. Traditional sociocultural gender stereotypes kept alive in fantasy can cause female analysts to subtly foreclose the impending threat of an intense erotic transference with male analysands due to a fear of outwardly directed male aggression. It is suggested that the maternal/containing transference can be unconsciously fostered by both analyst and analysand to defensively avoid expression of the aggressivized erotic transference in its full intensity. Similarities and differences in cases of sexual boundary violations with opposite-gender pairings are discussed. PMID- 17354496 TI - Two to Tango: commentary on Celenza. PMID- 17354497 TI - Alternate pathways to parenthood. PMID- 17354498 TI - Mothers and daughters. PMID- 17354499 TI - Psychoanalysis with an adopted child. PMID- 17354500 TI - "Freud" and Bullitt: an unknown manuscript. AB - An English translation of a previously unknown manuscript by Freud is presented. The manuscript, originally prepared in 1931 for William Bullitt's psychobiography of Woodrow Wilson, provides a general theoretical introduction to psychoanalysis. It also includes an original interpretation of Christianity that postulates a deep-going continuity between Christ identification and latent homosexuality. An editorial introduction to the translation clarifies the nature and limits of Freud's involvement with Bullitt's controversial psychobiography. PMID- 17354501 TI - An analog study of envy. PMID- 17354502 TI - Aims and outcomes of psychoanalysis. PMID- 17354503 TI - Assessing the quality of randomized controlled trials of psychodynamic psychotherapy. PMID- 17354504 TI - Expanding the evidence base for the cost-effectiveness of long-term psychoanalytic treatment. PMID- 17354505 TI - Measuring transference phenomena with fMRI. PMID- 17354506 TI - The development of a measure to assess putative mechanisms of change in the treatment of borderline personality disorder. PMID- 17354507 TI - Psychodynamic therapy for borderline personality disorder and co-occurring alcohol use disorders: a newly designed ongoing study. PMID- 17354508 TI - Psychodynamic therapy for oppositional defiant disorder: changes in personality, object relations, and adaptive function after six months of treatment. PMID- 17354509 TI - Reflective functioning in panic disorder patients: a pilot study. PMID- 17354510 TI - Do psychiatry residents obtain informed consent for psychotherapy? PMID- 17354511 TI - Psychotherapists in the community: reported prototypical psychodynamic treatments of trauma. PMID- 17354512 TI - What works, when, and why: an outcome study of psychodynamic psychotherapy. PMID- 17354513 TI - Treatment of metastatic colorectal cancer: from cytotoxic agents to molecular agents and multitargeted strategies. AB - Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in United States. For nearly 50 years, fluorouracil has been the only anticancer drug proven to benefit patients with metastatic CRC (mCRC), and it continues to be the backbone on which most treatment regimens are built. In the past 10 years, development of the topoisomerase I inhibitor irinotecan (Camptosar), the third-generation platinum analog oxaliplatin (Eloxatin), and the oral fluoropyrimidine capecitabine (Xeloda) advanced mCRC treatment and opened up an era of combination chemotherapy. More recently, monoclonal antibodies such as bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix) have become available for use in mCRC treatment in combination with cytotoxic agents and as monotherapies. The addition of these targeted agents to the mCRC treatment armamentarium has resulted in more therapeutic options and improved treatment outcomes for the patients. The prospect of mCRC treatment is ever promising as more targeted agents such as vatalanib are being introduced and as intelligent combination regimens are being designed based upon a better understanding of pharmacokinetics. In this article we review various treatment options, including cytotoxic and targeted agents, currently available for patients with mCRC. PMID- 17354514 TI - Recognizing and managing toxicities of molecular targeted therapies for colorectal cancer. AB - Traditional therapeutic concepts and treatment regimens for colorectal cancer are currently changing with the demonstration of the efficacy of biologic agents in this disease setting. The addition of the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin) to conventional chemotherapy in the first- and second-line settings has shown a survival benefit; this outcome has helped to rapidly change the standard of care. Other targeted agents, such as anti-epidermal growth factor receptor (EGFR) antibodies, have shown proof of efficacy in colorectal cancer as well. The molecular targeted therapies are associated with toxicity profiles that are distinctly different from those seen with conventional chemotherapy. A notable difference is the absence of high risk for myelosuppression, diarrhea, or alopecia, which are common side effects of cytotoxic chemotherapy. This article will explore the toxicities associated with targeted therapies in detail in an attempt to provide assistance to the practicing oncologist in detecting and managing these side effects in their patients. In particular, the article will focus on the side effects associated with the three currently approved targeted drugs: the anti- VEGF monoclonal antibody bevacizumab and the anti-EGFR monoclonal antibodies cetuximab (Erbitux) and panitumumab (Vectibix). PMID- 17354515 TI - Clinical selection of candidates for mutational testing for cancer susceptibility. AB - Advances in molecular genetics have evolved at such a fast pace that physicians may be bewildered about their clinical translation into patient care. However, genetic counselors, particularly those trained in cancer genetics, have been extremely helpful. The challenge to the physician, however, calls for an understanding of the natural history of hereditary cancer syndromes, which is often reflected in the pedigree. Pedigree/family history information must be compiled in sufficient detail to arrive at the most likely hereditary cancer syndrome diagnosis so that the molecular geneticist can search for the mutation. Finally, the challenge to the clinician is melding this into an accurate diagnosis, in order to provide highly targeted screening and management for high risk patients. This article is an attempt to crystallize all of these issues in a format that will help physicians-particularly those in the oncology community-to meet this challenge effectively. PMID- 17354516 TI - [Prostate cancer: synopsis of the American Urological Association (AUA) 2006]. AB - The 2006 annual American Urological Association (AUA) meeting took place in Atlanta from 20-25th of May. Four hundred and seventy nine abstracts (27.8%) were dedicated to the prostate cancer. The aim of this study is to summarise the most debated topics and to highlight the most original research. The main topics this year were obesity, ethnicity, PSA kinetic, surgical margins, robot and adjuvant therapy. PMID- 17354517 TI - Cardiometabolic risk modification: current trends and emerging therapies. PMID- 17354518 TI - Battlefield advanced trauma life support: 1. PMID- 17354519 TI - Natural considerations for skin of color. AB - Changing US demographics indicate that dermatologists will treat an increasing number of individuals of color. Early research on cutaneous anatomy and physiology was performed mostly in white populations. However, new research is elucidating similarities and differences in skin of color and white skin with regard to skin barrier, pigmentation, and sensitivity. Two of the most important issues are skin lightening and brightening. Products for use on skin of color typically should be gentle because of the proclivity of more deeply pigmented skin to develop pigmentary abnormalities in response to skin irritation or trauma. Increasing patient interest in natural remedies has been matched by research on the use of natural ingredients in dermatology. The relative gentleness of many of these products, coupled with excellent efficacy, makes natural ingredients such as soy and licorice excellent choices in the treatment of disorders such as postinflammatory hyperpigmentation (PIH) and melasma. For daily skin care, ingredients such as oatmeal and feverfew are good choices for gentle cleansing and moisturizing of dry, sensitive, or ashy skin. Sun protection is an increasing concern due to rising rates of melanoma. Several botanical products are useful in augmenting photoprotection with conventional sunscreens. PMID- 17354520 TI - Progress toward implementation of integrated systems for surveillance of HIV infection and morbidity in the United States. PMID- 17354521 TI - Striving toward comprehensive HIV/AIDS surveillance: the view from New York City. PMID- 17354522 TI - Public goods, private data: HIV and the history, ethics, and uses of identifiable public health information. PMID- 17354523 TI - HIV behavioral surveillance in the U.S.: a conceptual framework. AB - This article describes a conceptual framework for HIV behavioral surveillance in the United States. The framework includes types of behaviors to monitor, such as risk behaviors, HIV testing behaviors, adherence to HIV treatment, and care seeking for HIV/AIDS. The framework also describes the population groups in which specific behaviors should be monitored. Because the framework is multifaceted in terms of behaviors and populations, behavioral data from multiple surveillance systems are integrated to achieve HIV behavioral surveillance program objectives. Defining surveillance activities more broadly to include behavioral surveillance in multiple populations will provide more comprehensive data for prevention planning, and lead to a more effective response to HIV/AIDS in the United States. PMID- 17354524 TI - HIV behavioral surveillance among the U.S. general population. AB - HIV behavioral surveillance in the United States is conducted among three groups: infected populations, high-risk populations, and the general population. We describe the general population component of the overall U.S. HIV behavioral surveillance program and identify priority analyses. This component comprises several data systems (ongoing, systematic, population-based surveys) through which data on risk behaviors and HIV testing are collected, analyzed, and disseminated. Multiple data systems are needed to balance differences in scope and purpose, as well as strengths and weaknesses of the sampling frames, mode of administration, and frequency of data collection. In a concentrated epidemic, such as in the United States, general population data play a small but important role in monitoring the potential spread of infection more broadly, particularly given increases in HIV transmission through heterosexual contact. PMID- 17354525 TI - Behavioral surveillance among people at risk for HIV infection in the U.S.: the National HIV Behavioral Surveillance System. AB - The Centers for Disease Control and Prevention, in collaboration with 25 state and local health departments, began the National HIV Behavioral Surveillance System (NHBS) in 2003. The system focuses on people at risk for HIV infection and surveys the three populations at highest risk for HIV in the United States: men who have sex with men, injecting drug users, and high-risk heterosexuals. The project collects information from these three populations during rotating 12 month cycles. Methods for recruiting participants vary for each at-risk population, but NHBS uses a standardized protocol and core questionnaire for each cycle. Participating health departments tailor their questionnaire to collect information about specific prevention programs offered in their geographic area and to address local data needs. Data collected from NHBS will be used to describe trends in key behavioral risk indicators and evaluate current HIV prevention programs. This information in turn can be used to identify gaps in prevention services and target new prevention activities with the goal of reducing new HIV infections in the United States. PMID- 17354526 TI - Surveillance of HIV risk and prevention behaviors of men who have sex with men--a national application of venue-based, time-space sampling. AB - In collaboration with the Centers for Disease Control and Prevention, participating state and local health departments, universities, and community based organizations applied venue-based, time-space sampling methods for the first wave of National HIV Behavioral Surveillance of men who have sex with men (NHBS-MSM). Conducted in 17 metropolitan areas in the United States and Puerto Rico from November 2003 through April 2005, NHBS-MSM methods included: (1) formative research to learn the venues, times, and methods to recruit MSM; (2) monthly sampling frames of eligible venues and day-time periods that met attendance, logistical, and safety criteria; and (3) recruitment of participants in accordance with randomly generated venue calendars. Participants were interviewed on HIV risk and prevention behaviors, referred to care when needed, and compensated for their time. By identifying the prevalence and trends of HIV risk and prevention behaviors, NHBS-MSM data may be used at local, state, and federal levels to help obtain, direct, and evaluate HIV prevention resources for MSM. PMID- 17354527 TI - Developing an HIV behavioral surveillance system for injecting drug users: the National HIV Behavioral Surveillance System. AB - While disease surveillance for HIV/AIDS is now widely conducted in the United States, effective HIV prevention programs rely primarily on changing behavior; therefore, behavioral data are needed to inform these programs. To achieve the goal of reducing HIV infections in the U.S., the Centers for Disease Control and Prevention, in cooperation with state and local health departments, implemented the National HIV Behavioral Surveillance System (NHBS) for injecting drug users (IDUs) in 25 selected metropolitan statistical areas (MSAs) throughout the United States in 2005. The surveillance system used respondent-driven sampling (RDS), a modified chain-referral method, to recruit IDUs for a survey measuring HIV associated drug use and sexual risk behavior. RDS can produce population estimates for specific risk behaviors and demographic characteristics. Formative assessment activities-primarily the collection of qualitative data-provided information to better understand the IDU population and implement the surveillance activities in each city. This is the first behavioral surveillance system of its kind in the U.S. that will provide local and national data on risk for HIV and other blood-borne and sexually transmitted infections among IDUs for monitoring changes in the epidemic and prevention programs. PMID- 17354528 TI - Use of rapid behavioral assessments to determine the prevalence of HIV risk behaviors in high-risk populations. AB - Rapid HIV Behavioral Assessment (RHBA) is a method for collecting much-needed information about sexual, drug-use, and HIV testing behaviors from people at high risk for HIV infection in areas with low-to-moderate HIV prevalence. During 2004, RHBAs were conducted in seven small to moderate-sized cities in the United States during Gay Pride events. Anonymous 10-minute interviews were administered to eligible attendees using handheld computers. Depending on the city, between 47% and 97% of individuals approached agreed to hear more about the survey. Enrollment rates exceeded 90% in every location. RHBAs conducted during 2004 were well received by the gay and public health communities. They were simple to organize and administer, flexible, and cost-efficient, suggesting that this approach holds promise for expansion to additional high-risk groups and geographic locations. RHBAs can provide state and local health departments with demographic and behavioral data that can be used to design, target, and evaluate local HIV prevention programs. PMID- 17354529 TI - The status of national HIV case surveillance, United States 2006. AB - Since the height of HIV incidence in the mid-1980s, advances in treatment have delayed progression of HIV infection. As a result, surveillance of AIDS cases alone is no longer sufficient to monitor the current status of the HIV epidemic. At the national level, new HIV diagnoses and progression of these cases to AIDS are used to describe the epidemic. The capacity to monitor the national HIV epidemic has consistently improved over the last several years. An increasing number of states report diagnosed HIV cases to the national surveillance system, allowing data from this system to better represent the national picture. Monitoring the national HIV epidemic depends on a nationwide system using standardized methods of data collection, and establishing such a comprehensive system remains one of the highest priorities for national HIV case surveillance. PMID- 17354530 TI - Monitoring the incidence of HIV infection in the United States. AB - The Centers for Disease Control and Prevention maintains a national surveillance system that provides data about the HIV/AIDS epidemic for program planning and resource allocation. Until recently, incidence of HIV infection (i.e., the number of individuals recently infected with HIV) has not been directly measured. New serologic testing methods make it possible to distinguish between recent and long standing HIV-1 infection on a population level. This article describes the new National HIV Incidence Surveillance System. PMID- 17354531 TI - [Thomas Zeltner, director of the OFSP: "How to fight the gloominess of medical professions?"]. PMID- 17354532 TI - [New concepts for the therapy of systemic lupus erythematosus]. AB - Immediate, short- and long-term adverse events of classical immunosuppressor drugs strongly stimulate novel, but less toxic approaches. Combined or sequential use of cyclophosphamide, mycophenolate mofetil and/ or azathioprine should improve clinical tolerance and avoid severe adverse events (infections, infertility, amenorrhea), regularly associated to long term therapies with classical immunosuppressive schemes. Among novel developments based on biologicals, the anti-CD20 monoclonal antibody rituximab (anti-B cells) appears encouraging in open studies, in association or not with cyclophosphamide, and is generally well tolerated. Further information is expected from the inhibitor of T cell/B cell co-stimulation CTLA4-Ig, or from strategies aiming to inhibit key cytokines in SLE pathogenesis such as interferon-alpha, IL-1 or IL-6. PMID- 17354533 TI - [New trends in asthma therapy: is there a place for biologicals in 2007?]. AB - Initiatives like GINA (Global Initiative for Asthma) permitted to better define epidemiological and physiopathological data in asthma, and to classify asthma severity based on clinical criteria. However, a small proportion of asthmatic patients remains symptomatic even with a well adjusted treatment. This refractory asthma phenotype is probably associated with heightened neutrophilic airway inflammatory response, tissue injury and remodelling. Recent studies investigated new therapeutic aspects related to causative (allergy for instance) or inflammatory (TNF-alpha) aspects of refractory asthma. Even though these new biological treatments are very expensive, they could be cost effective in case of demonstrated efficacy since patients with severe refractory asthma account for a substantial proportion of the health costs. PMID- 17354534 TI - [Cell therapies in cardiology: results from the first randomized clinical trials]. AB - Following acute myocardial infarction, necrotic cardiac tissue is replaced by scar leading to ventricular remodeling and pump failure. Transplantation of autologous bone marrow-derived cells into the heart, early post-infarct, aims to prevent ventricular remodeling. This strategy has been evaluated in four controlled, randomized clinical trials, which provided mixed results. A transient improvement in ventricular function was observed in one trial, and a modest improvement (the duration of which remains to be determined) in an additional trial, whereas two trials showed negative results. A modest benefit of bone marrow cell transplantation was also observed in patients with chronic ischemic heart disease. Despite mixed results reported so far, cell therapy of heart disease still is in its infancy and has considerable room for improvement. PMID- 17354535 TI - [Surgery]. AB - Indications for minimal invasive surgery are increasingly numerous. The treatment of oesophageal cancer presents a significant example. New multidisciplinary modalities allow, from now on, to push back the limits and to improve the results of hepatobiliary surgery. Several studies show a decrease in the significance of age but underline the importance of comorbodities among elderly patients, and therefore significantly increase indications to pancreatic, hepatic or colorectal surgery in this age group. Elective laparoscopy is now accepted without age limit. Sacral nerve stimulation is an important alternative to classical treatment of fecal incontinence. Peripheral transcutaneous neuromodulation for this condition is effective on both continence and quality of life. PMID- 17354536 TI - [Addiction]. AB - This year review emphasizes three aspects coming from addiction psychiatry: 1. Psychosis and cannabis: a motivational approach. 2. Connection between addiction services and psychiatric wards. 3. Use of antiepileptic agents in addiction medicine. PMID- 17354537 TI - [Dermatology]. AB - We are going over therapeutic acquisitions in a club-journal including relevant publications in different fields: mecanisms of action, therapeutic perspectives in a near future, and side effects. PMID- 17354538 TI - [The DREAM of diabetes prevention]. AB - This article summarizes an important study published in 2006 in the field of the prevention of diabetes mellitus. It is the DREAM study which evaluate the therapeutic effects of rosiglitazone and ramipril versus placebo in the prevention of type 2 diabetes in high risk patients: glucose intolerance or impaired fasting glucose. In this clinical study, more than 5000 patients were followed during 3 years. The risk of diabetes was reduced with rosiglitazone of 62% (NNT 9). In the field of negative effects the risk of cardiac insufficiency was multiplied by 7 (NNH 250) but stayed a rare event (to 0,5% of the treated subjects). The ramipril had no preventive effect for the prevention of type 2 diabetes but induced a higher frequency of return towards the normoglycaemia. This treatment can be recommended for these high risk subjects. PMID- 17354539 TI - [Intravitreal anti-VEGF injections improve the visual prognosis of wet age related macular degeneration]. AB - Age related macular degeneration (AMD) is an ocular disease with high prevalence among elderly persons. Two different forms exist: dry AMD, usually slowly progressive, and neovascular AMD (wet form) more aggressive. Photodynamic therapy is used to treat the wet form and anti VEGF treatments recently became available and offer a real change in the prognostic of wet AMD. Two products are registered and used in Switzerland (Macugen and Lucentis), a third "off labels product", Avastin is also currently used in clinical practice. Nevertheless, both the duration of treatment and the number of injection requested to stabilise the disease were not defined in the studies. Ongoing studies are mainly evaluating combined treatments and long acting form of the drug. PMID- 17354540 TI - [ENT]. AB - Our present choice of papers will cover various generalist aspects of our speciality. We will report on the importance of biofilms, the role of helicobacter in otitis media, de role of fungi in sinusal disease, or on the increase of MRSA in neck abscesses. Treatments of mycotic otitis and middle ear infection, sudden hearing loss, or acute ethmoiditis in children will be described. The interest of tonsillectomy, dacryocystorhinostomy or preservation radiotherapy will be also discussed. PMID- 17354541 TI - [Osteoporosis treatment]. AB - The diagnosis threshold of osteoporosis is based on low bone density value. The therapeutic threshold is modulated by clinical risk factors. Denosumad, an antibody raised against RANK-Ligand, is a potent bone resorption inhibitor. Efficacy on the reduction of fracture incidence is well documented with 800 IU of vitamin D and 1 g of calcium per day. Tibolone (Livial) prevents vertebral fractures but increases strokes. Strontium ranelate (Protelos) prevents fractures over 5 years duration even in women older than 80. Native parathormone (84AA) (Preotac), reduces vertebral fractures. Alendronate (Fosavance), monthly oral and trimonthly i.v. Ibandronate (Bonviva) are the new possibilities of treatment with bisphosphonates. Yearly i.v. zoledronate injections prevent any kind of osteoporotic fractures. PMID- 17354542 TI - [Pediatry]. AB - During the previous year, several changes occurred in paediatric patient's management. The new PALS recommendations redefine the rhythm and the rate between cardiac massage and ventilation as well as the indications for defibrillation. The choice of the test for Helicobacter Pylori depends on the age of the patient and on the clinical situation. New anti-hypertensive drugs allow to limit the progression of chronic renal disease with hyper-tension and/or proteinuria. The choice between immunoglobulins, steroids, splenectomy and rituximab to treat chronic thrombocytopenic purpura treatment is a therapeutic challenge. Finally, a new approach is presented for diagnosis and treatment of iron overload in chronic hemoglobinopathies. PMID- 17354543 TI - [Psychiatry]. AB - Introduced this year on the Swiss market, duloxetine (Cymbalta) is a new antidepressant which inhibits the reuptake of noradrenaline and serotonin. Clinical studies have shown its efficacy in depression as well as in neuropathic pains (60-120 mg/day) with a good tolerability. In this paper are also included short reviews about the two large American studies developed by the National Institute of Mental Health in the fields of the treatment for depression (STAR-D) and of the antipsychotic treatments for schizophrenia (CATIE study). Its also reviews two questions of present interest: the use of the second generation antipsychotics for the treatment of bipolar depression and the concept of bipolar disorders in children. PMID- 17354544 TI - [Urology]. AB - This reviewed publication summarized the newly therapeutic procedures in different urological pathologies. In the treatment of benign prostate hyperplasia (BPH), laser KTP with high power is now becoming a standard. For small benign testicle lesions, the surgical biopsy under echographic control avoid radical orchidectomy. In non-invasive bladder cancer, Hexvix fluorescence is gaining a wide acceptance. In invasive bladder cancer, new protocols of neoadjuvant chemotherapy demonstrate an increased interest. In renal cancer, immunomodulation and angiogenesis molecules seem to offer some hopes for advanced tumors. In bladder dysfunctions such as hyperactive bladder, new molecules have widens the range of the available treatments. PMID- 17354545 TI - [Facing the bodies from Amsterdam]. PMID- 17354546 TI - [On the right to know one's genetic origins (2)]. PMID- 17354547 TI - [The efficacy of adjuvant trastuzumab is confirmed in certain breast neoplasms]. PMID- 17354548 TI - [Asperger syndrome: neuroimaging ]. PMID- 17354549 TI - [Asperger syndrome; the issue and the truth]. AB - In recent years, Asperger disorder became a key issue in Japan. Serious crimes which have been caused by high-functioning PDD adolescents have become a social problem. Total population study of PDD showed the increase of these children, and the most recent study reported the prevalence to be 2%, in Nagoya City. Now, we have at least one PDD in every school class. It poses a serious problem for Japanese school education. On the other hand, it had gradually become apparent that there are many PDD adult who had been misdiagnosed with other psychiatric disorders; schizophrenia, BPD and so on. The author discusses the relevant issue of Asperger disorder and high-functioning PDD from a clinical perspective. PMID- 17354550 TI - [Autistic psychopathy or pervasive developmental disorder: how has Asperger's syndrome changed in the past sixty years?]. AB - Bosch (1970) was the first author who used "Asperger's syndrome" in English literature. In those days, "Kanner's syndrome" i.e. autism, which had been under schizophrenic-versus-undeveloped arguments from the 1960's, was always contrasted with Asperger's "autistic psychopathy in children". From then on there have been vicissitudes over the notion of "Asperger's syndrome" and its clinical presentation. Nowadays, the restricted notion of "Asperger's syndrome" is dominant and used in both DSM-IV-TR and ICD-10. However, debates concerning the aspect of Asperger s "psychopathy" in clinical study and practice have long disappeared. In daily life, when we describe someone as "like Asperger's", it means a personality deviation that is to the degree of Asperger's "psychopathy". The history of Asperger's "psychopathy" is still developing in our culture. PMID- 17354551 TI - [Epidemiology of Asperger's syndrome]. AB - Only a little data is available so far on the prevalence of Asperger's syndrome. The prevalence that Fombonne (2003) estimated after considering six European research was 2/10,000. In Ishikawa's study (2006) conducted in Nagoya city, Japan, the prevalence of Asperger's syndrome was 56/10,000. Currently there are not strict diagnostic criteria of Asperger's syndrome and methods of investigation are not consistent in each study. Therefore the prevalence rate for Asperger's syndrome covered very wide range. Although we still don't have a precise prevalence data on Asperger's syndrome, the awareness of this syndrome emerged in these several decades tells us that further research and support for the children of Asperger's syndrome and their family are necessary. PMID- 17354552 TI - [Asperger's syndrome and medical care]. AB - Asperger's syndrome has been recognized recently. Diagnosis is done by DSM-IV-TR, ICD-10 or Autistic Spectrum Diagnosis. Medical care is performed by adjustment of environmental atmosphere, educational treatment and/or medication. Patients are cured by parents or teachers who can understand their thinking or behavior pattern. Educational treatment is important to compensate the lack of "mind of theory", of integration of central nervous system and of executive functioning. Medication is applied only secondary symptoms, such as hallucinated or delusional complaints or change of mood or compulsive behavior. Some of this syndrome's patients have excellent abilities and will accomplish great achievement in adult. We need protect them from bullying or secondary social withdrawal in adolescent age. PMID- 17354553 TI - [Neurological background of Asperger's disorder and other pervasive developmental disorders]. AB - The core features of pervasive developmental disorder (PDD) are impairment in social interaction and restricted ranges of interest and activities with obsessive/compulsive traits. Clinical characteristics of PDD range across a variety of psychophysiological areas, from vigilance and autonomic arousal through attention to higher cognitive functions such as memory and language. The author reviewed hypotheses on the neurological background of PDD, which includes brainstem, cerebellum, prefrontal cortex, mirror neuron system, and amygdala and related circuit. Among them, the amygdala hypothesis appears to be most successful in explaining the core feature of PDD, i.e. social impairment. It is expected that advance in cognitive neuroscience on social behavior will clarify the link between neurological and clinical findings of Asperger's disorder. PMID- 17354554 TI - [Environmental factors in Asperger syndrome]. AB - This paper reviews what is currently known about the environmental factors in Asperger syndrome that is a neurodevelopmental disorder of genetic origins. Its characteristics tend to occur in families of those with the syndrome. The rate of complications during pregnancy or the neonatal period in the patients with Asperger syndrome was about the same as that in the control group. It is true that their involvement in their outer world could not influence the core social deficits very much. But it might facilitate the appearance of the second symptoms such as dissociation, anxiety, depression, persecutory delusion as well as antisocial behavior including serious criminal acts. PMID- 17354555 TI - [Genetic factors in Asperger syndrome]. AB - Asperger syndrome (or Aperger's disorder) is one of the syndromes of autism spectrum disorders (ASD) (or pervasive developmental disorder). Twin and family studies have indicated that genetic factors play a significant role in the development of ASD, including "classical" autism, in a complicated fashion of inheritance. The role may be more significant than in other major psychiatric disorders. Genome-wide linkage studies and cytogenetic studies suggest several chromosomal regions, including 2q, 7q and 15q, for linkage with autism and ASD. While the 7q region is considered the most promising in autism, linkage studies in Asperger syndrome have failed to observe its linkage to this region. Whether the genetic studies should be conducted separately in Asperger syndrome or in the entire ASD might be an issue of discussion for future studies. PMID- 17354556 TI - [Advances in neuroimaging research on Asperger syndrome]. AB - Autism spectrum disorder (ASD) (i.e., autism and Asperger syndrome) is a neurodevelopmental disorder, although its etiology is still unclear. Neuroimaging studies have attempted to identify the neurobiological basis of ASD. This article reviews recent progress in ASD research using magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). MRI studies documented structural and functional abnormalities in cerebella, the frontal lobes, the temporal lobes, and limbic systems of individuals with ASD. SPECT and PET studies suggested that abnormalities of the serotonergic system, in addition to decreased regional cerebral blood flow in the frontal and temporal lobes, are implicated in the pathophysiology of ASD. PMID- 17354557 TI - [Impairment of social interaction, coordination disorder, and hypersensitivity in Asperger's syndrome]. AB - Asperger's syndrome is not accompanied with intellectual disability, however it has social impairments as well as autism and demonstrates failure to develop peer relationships according to each life stage. Social reciprocal behavior deficits are revealed typically during childhood. On the other hand, after school age these deficits are modified by environmental factors that may induce secondary disorders consequently. Hypersensitivity and coordination disorder, which are not included in diagnostic criteria for Asperger's syndrome, are often in presence. These symptoms are diminished and rarely interfere daily living as growth. However they may keep Asperger's syndrome individuals from adapting to others, so we need to take it into consideration. PMID- 17354558 TI - [Pragmatic impairments in individuals with Asperger syndrome: characteristics and interventions]. AB - Researches on pragmatic impairments in individuals with Asperger syndrome were reviewed in regard to its characteristics and interventions. The very wide diversity of their pragmatic impairments was studied in terms of speech acts, expressing mental states, comprehension of indirect speech, question and answer, conversational turn-taking, narratives, pronouns and addressing forms, inferential language, reference and cohesion, and humor and joke. As for theories on background of the impairments, theory of mind and relevance, central coherence, executive function, general semiotic deficit, and others were discussed. Then, intervention techniques were outlined. Those were social stories, social skills training, teaching theory of mind, individual and group interventions from socio-pragmatic viewpoint. PMID- 17354559 TI - [Psychiatric comorbidities and secondary emotional difficulties in Asperger syndrome]. AB - People with developmental disorders frequently have psychiatric comorbidities and problematic emotional reactions and behaviors. We commonly calls these conditions "nizi-shougai (secondary difficulties)" in Japan. But there is no clear definition of "nizi-shougai", and it is impossible to distinguish "secondary difficulties" from the problems derived from Asperger syndrome itself. In this paper, I focus on psychiatric comorbidities and emotional difficulties of Asperger syndrome. Early detection and intervention for children with developmental disorders can prevent some kind of "secondary difficulties". Treatment for Asperger syndrome should be tailored to meet individual characteristics and needs. PMID- 17354560 TI - [Diagnostic criteria for Asperger syndrome]. AB - The diagnostic criteria for Asperger syndrome (AS) are still controversial. ICD 10 and DSM-IV are usually used as a formal diagnostic criteria for AS. However, many papers point out there are many problems in ICD-10/DSM-IV. It is indicated that the diagnosis of AS using ICD-10/DSM-IV criteria is virtually impossible due to the rule of onset and precedence. ICD-10/DSM-IV criteria don't include core symptoms of AS, such as odd speech and limited intelligent interests reported by Hans Asperger. Most of the cases which are diagnosed as AS clinically meet the diagnostic criteria for autism or atypical autism(PDD-NOS) in ICD-10/DSM-IV. ICD 10/DSM-IV criteria is too narrow to diagnose AS. This causes much confusion and disadvantage for families, clinicians and researchers. We need to establish the clinically useful and reliable diagnostic criteria for AS. PMID- 17354561 TI - [Early detection of and diagnostic tools for Asperger's disorder]. AB - Case identification of children with high-functioning pervasive developmental disorders (HFPDD) including Asperger's disorder tends to be delayed. A delay of case identification prevent from access to early intervention for children and parents. Although early diagnosis of HFPDD is difficult and less sensitive at present, several objective evaluation scales, such as CARS, ADOS-G and ADI-R, can be applied to very young children and are found to be relatively sensitive and stable. Recently autism-specific screening tools, such as the Checklist for Autism in Toddlers (CHAT), the Modified Checklist for Autism in Toddlers (M CHAT), have been developed. The current research using the Japanese version of the M-CHAT and its clinical use combined with the infant health check-up system are described. PMID- 17354562 TI - [Diagnosis of Asperger syndrome in infancy and childhood]. AB - I discussed, in this chapter, the possibilities and limitations of clinical diagnosis for Asperger syndrome (AS) in infancy and early childhood. For early diagnosis or simply noticing the possibility of AS, clinicians should be sensitive to the auxiliary conditions of AS such as motor dysfunction and sensory/sleep disturbances during the early stage of life, as well as the incipient representations of the main AS symptoms in the diagnostic criteria, such as lack of reciprocal social interaction or joint attention. Future prospective study with large cohort, or creation of the new methods for cognitive evaluation which is applicable to infants and toddlers, would be profitable in order to establish the sensitive tool for AS diagnosis in early infancy, while the idea would be expected undoubtedly elusive. PMID- 17354563 TI - [Differentiation between childhood autism and Asperger's syndrome]. AB - According to the DSM-IV, the autism diagnosis always has priority over the Asperger syndrome (AS). If a patient meets the criteria for autism, the diagnosis of AS is ruled out. However, since Lona Wing reexamined Asperger's original description and noted the similarities between autism and AS, whether autism, especially high-functioning autism (HFA), and AS were the same disorder or not has been controversial. There is no reason why we distinguish HFA from AS with regard to general intervention and social and communication skill training. From a view point of clinical features, cognitive neurophychology and neurobiology, the differentiation between HFA and AS is not clear. There are few reports on outcome in HFA and AS. Whereas, it is suggested that HFA and AS may be different in social problems such as suicide attempt. Researches on the differentiation between HFA and AS are to be needed in future. PMID- 17354564 TI - [Non-verbal learning disabilities]. AB - In 1975, Myklebust proposed a special form of learning disabilities characterizes by impairment of spatial cognition, social interaction and conceptualization, and named it as non-verbal learning disabilities (NLD). Since the brain locus for spatial cognition was thought to be localized in the right hemisphere, NLD was regarded as a disorder of the right hemispheric function. The clinical characteristics of NLD are almost identical to those of Asperger syndrome (AS), which was introduced in English literature in 1981. Since Asperger syndrome is regarded as one of the autistic spectrum disorders, and autism was once regarded as the left hemispheric dysfunction, it has long been believed that NLD and AS are clinically different entities. However, their clinical similarities have raised a growing opinion that these two disorders are probably identical or at least closely related. PMID- 17354565 TI - [Differential diagnosis between pervasive developmental disorder and schizophrenia]. AB - Differential diagnosis between schizophrenia and pervasive developmental disorder (PDD) including Asperger's syndrome, needs evaluation of apparently similar symptoms among the two disorders and careful collection of information about developmental history of each patient. Some conditions that have been traditionally regarded as schizophrenia, seem to have overlapping parts with those of PDD. An example of them is schizophrenia--like symptoms observed occasionally in individuals with PDD. The relationship of the two disorders remains to be investigated. I present a case of an adolescent with early symptoms of schizophrenia, in whom there seems to have been PDD symptoms in his early childhood. The issue of the differential diagnosis of the two disorders is discussed on the basis of the case. It is sometimes difficult to diagnose PDD in mildest cases in adolescence or adulthood, presumably because they show subtle symptoms in their early childhood in terms of interpersonal relationships and caretakers of them are likely to fail to recognize their problems, which may cause difficulty in sufficient collection of information about their early childhood. PMID- 17354566 TI - [Personality disorder]. AB - Differentiating between diagnoses of Asperger's syndrome and personality disorders is difficult because of the symptomatology of these disorders and due to the following methodological problems: 1) Developmental disorders, including Asperger's syndrome, are diagnosed in consideration of the time course, while personality disorders are cross sectional entities: 2) The distinction between both becomes more difficult according to the specific operational diagnosis system used. 3) Differentiating between these diagnoses is difficult because data regarding the developmental problems of adult patients with Asperger's syndrome are rare. In consideration of such problems, differential diagnoses between Asperger's syndrome and some types of personality disorder, namely schizoid, schizotypal, borderline, anankastic and avoidant types are discussed. Furthermore, the antisocial tendencies of Asperger's syndrome are also discussed. PMID- 17354567 TI - [Similarities and differences between the behavior of Asperger's syndrome and obsessive-compulsive disorder]. AB - Asperger's syndrome (AS) is one of subcategories of pervasive developmental disorder defined by behavioral symptoms. These symptoms include repetitive and stereotyped patterns similar to the behavior of obsessive-compulsive disorder(OCD). These are included by a broader concept newly named as obsessive compulsive spectrum disorders. While there may be biological bases common to the repetitive behaviors of PDD and OCD, differential diagnosis is important from the clinical point of view. Most of the obsession-like and compulsion-like behaviors of the former lack ego-dystonic features. Moreover, AS has no clinically significant delay in language in definition, but has pragmatic disorder, which should not be seen in OCD. PMID- 17354568 TI - [TEACCH]. AB - TEACCH Program found in North Carolina forty years ago has been developed and spread out all over the world for it's effectiveness. People with developmental disorders and autism have been given life-long support and collaboration to live and work together with people around them in their community with the principle and practical methods of visual-structuring through the program. PMID- 17354569 TI - [Behavior analytic approach to Asperger syndrome]. AB - We describe the behavior analytic approach to helping people with Asperger syndrome regarding social interaction and communication issues. In the behavior analytic approach, the cause of maladaptive behavior is not attributed to the disability itself. Maladaptive behaviors are viewed as a function of the interaction between an individual and the environment. Therefore, we assess these functional relationships and intervene by modifying aspects of the environment. Functional assessment is one of the most effective methods to evaluate the cause of problem behaviors and helps in the selection of an intervention strategy. We teach students functionally equivalent alternative behaviors that are socially appropriate and yet met the needs of the individual. Furthermore, we discuss the importance of teaching individuals with Asperger syndrome critical skills, including communication skills, self-management skills, and how to deal with anxiety. PMID- 17354570 TI - [Pharmacologic treatment of Asperger syndrome]. AB - Asperger syndrome is associated with various dysfunctional and problematic behaviors, in addition to the core features of communication and social skills dysfunction that define these conditions. Although there is currently no pharmacologic cure for the core features of Asperger syndrome. This article discusses the various medications for the behavioral symptoms of Asperger syndrome, which include hyperactivity, aggression, tantrums, self-injury, depression, obsession and so on. Methylphenidate, SSRIs, atypical antipsychotics and mood stabilizer were introduced. PMID- 17354571 TI - [Toward providing individualized educational support for children with Asperger's disorder]. AB - In the present study, I examined educational support for children with Asperger' s disorder. From the viewpoint of individualized support and class-wide management, means of some effective educational support in regular education classroom was introduced. In the practice of individualized support, importance of the case meeting where teachers and parents participated in was pointed out. In addition, it was necessary to make support tools to realize effective support. On the other hand, in the practice of class-wide management, guidance of making human relations between children was one of the top priority problems. PMID- 17354572 TI - [Care and social treatment for parent(s) and children with Asperger syndrome]. AB - This paper describes the care and social treatment for parent(s) and child with Asperger syndrome. The children with Asperger syndrome are not easily distinguished from children without Asperger syndrome. The diagnosis can be varied depending on perspectives. They are more likely to receive inappropriate intervention due to lack of understanding. They are more likely to develop emotional and conduct problems secondarily. Because their disorders cannot be seen clearly, their difficulties are not identified. It seems that parent(s) and child with Asperger syndrome are hurt by this problem. It is difficult to operate parents' association and self-help group. They should learn it about one's diagnosis. While having a difference, an effort to live together is demanded. PMID- 17354573 TI - [Asperger syndrome in adolescence: The problem and appropriate treatment]. AB - I have described the corresponding method for bullying, independence and interpersonal relationships of company/opposite sex, thinking disorders caused by suffering damage or victimization and withdrawal and violence in the family among the problems in and in response to Asperger syndrome in adolescent cases. Psychotherapy is used for bullying and interpersonal relationship problems. Cognitive therapy and protective correspondence are more effective in bullying than the exposure method. It seems to be more effective to teach and instruct the corresponding principle as well as supportive response because interpersonal relationships are likely to involve failures. Pharmacological therapy was valid in feelings of paranoia and violence. Since the disorder has been recently conceptualized in pervasive developmental disorder, the scope of the subject has increased whereas Asperger syndrome used to be diagnosed in compliance with its classic examples. Therefore, it needs to clarify diagnostic examples based on new concepts, accumulate subject examples and verify the corresponding method with evidence. PMID- 17354574 TI - [Administrative support for Asperger's syndrome]. AB - In recent years, administrative support for developmental disabilities, such as Asperger's syndrome, has come to be conspicuous with "Law for Supporting Persons with Developmental Disabilities", which went into effect in 2005, and promotion of "Special Support Education". However, these supports are still insufficient, because administrative support for the Asperger's syndrome in Japan, having just started very recently. Developmental disabilities, such as Asperger's syndrome, are by no means mild as disabilities, it is required to fill up administrative support for them from now on. PMID- 17354575 TI - [Special support education for students with Asperger's syndrome]. AB - The necessity of an educational action on the child student with the Asperger's syndrome etc. started after 2001, and it became clearer in "big paradigm conversion from a current special education system to a new special support education system". Legal maintenance corresponding to "LD, ADHD, high-functioning autism etc." including the Asperger's syndrome became recent years, it come one after another, and the construction of the system of support began to advance rapidly in nationwide various schools. And, it started, and the construction of a continuing consistent system of support from the kindergarten to the high school began to materialize to the construction of the support system. PMID- 17354576 TI - [Regulatory T cell based transplant tolerance--freedom from immunosuppression]. AB - Tolerance after clinical transplantation (Tx) is still extremely rare. However, Kyoto elective protocol enabled a substantial number of patients to weaned off immunosuppression after liver Tx. This is referred to as an immunoprivilege. Nevertheless, the operating mechanisms for liver Tx tolerance remain elusive. The authors demonstrated that regulatory T cells (Tregs) are likely to play an important role in liver Tx tolerance. In addition, we found that precursor like Tregs exist in the human peripheral blood. This can propagate upon stimulation with allo-antigen, in contrast to anergic property of Tregs. Thus, the exploitation of precursor like Tregs as a cellular source of ex vivo and in vivo expansion may lead to the widespread clinical use of Tregs for Tx. PMID- 17354577 TI - [Atrial fibrillation and renin-angiotensin system]. AB - Many recent mega-trials regarding atrial fibrillation have failed to prove the efficacy of antiarrhythmic drugs to improve the mortality and morbidity of patients with atrial fibrillation. Meanwhile, the upstream therapy of atrial fibrillation, the management of many components that lead to atrial fibrillation, has been paid much attention to, because its target would be the causes of atrial fibrillation itself. Among many upstream therapies, the blockade of the renin angiotensin system would be promising from basic and clinical viewpoints, and also from rhythm management and stroke prevention. PMID- 17354578 TI - The future of interventional cardiology. PMID- 17354579 TI - Possible predictors of target lesion revascularization after drug-eluting stent implantation. AB - BACKGROUND: A small number of patients still need target lesion revascularization (TLR) after drug-eluting stent (DES) implantation. It is important for the management of coronary artery disease to assess the predictors of TLR after DES implantation. METHODS AND RESULTS: Two hundred ninety-seven patients (325 lesions) were treated with Cypher sirolimus-eluting and/or TAXUS paclitaxel eluting stent implantation at four centers in Japan and Brazil. Among these centers, 20 patients (24 lesions) needed clinically driven TLR. The clinical and angiographic characteristics of TLR patients were compared to those of non-TLR patients. Hemodialysis, prior myocardial infarction (MI) and prior coronary artery bypass grafting (CABG) were more frequent in TLR patients than in non-TLR patients. An ostial stenosis was more frequent in the TLR group than in the non TLR group (41.7% vs 19.9%, p=0.012). In addition, post-procedure in-stent percentage diameter stenosis (%DS) was higher in TLR patients (21.9% vs 13.3%, p = 0.002). Stepwise logistic regression analysis indicated that all of these variables were independent predictors of TLR after DES implantation. CONCLUSIONS: Hemodialysis, prior MI, prior CABG, ostial lesion location and high in-stent %DS may be independent predictors of TLR after DES implantation. PMID- 17354580 TI - [Evaluation of echocardiographic left ventricular wall motion analysis supported by internet picture viewing system]. AB - BACKGROUND: Assessment of deterioration of regional wall motion by echocardiography is not only subjective but also features difficulties with interobserver agreement. Progress in digital communication technology has made it possible to send video images from a distant location via the Internet. OBJECTIVES: The possibility of evaluating left ventricular wall motion using video images sent via the Internet to distant institutions was evaluated. METHODS: Twenty-two subjects were randomly selected. Four sets of video images (parasternal long-axis view, parasternal short-axis view, apical four-chamber view, and apical two-chamber view) were taken for one cardiac cycle. The images were sent via the Internet to two institutions (observer C in facility A and observers D and E in facility B) for evaluation. Great care was taken to prevent disclosure of patient information to these observers. Parasternal long-axis images were divided into four segments, and the parasternal short-axis view, apical four-chamber view, and apical two-chamber view were divided into six segments. One of the following assessments, normokinesis, hypokinesis, akinesis, or dyskinesis, was assigned to each segment. The interobserver rates of agreement in judgments between observers C and D, observers C and E, and intraobserver agreement rate (for observer D) were calculated. RESULTS: The rate of interobserver agreement was 85.7% (394/460 segments; Kappa = 0.65) between observers C and D, 76.7% (353/460 segments; Kappa = 0.39) between observers D and E, and 76.3% (351/460 segments; Kappa = 0.36)between observers C and E, and intraobserver agreement was 94.3% (434/460; Kappa = 0.86). Segments of difference judgments between observers C and D were normokinesis-hypokinesis; 62.1%, hypokinesis-akinesis; 33.3%, akinesis-dyskinesis; 3.0%, and normokinesis akinesis; 1.5%. CONCLUSIONS: Wall motion can be evaluated at remote institutions via the Internet. PMID- 17354581 TI - Current disparities in the prices of medical materials between Japan and the United States: further investigation of cardiovascular medical devices. AB - OBJECTIVES: Prices of medical devices in Japan were previously reported to be 2 to 4 times higher than those in the United States in 1996 and 1997. However, such data are out of date. We previously compared the market prices in early 2005 between Japan and the US for 16 items in 10 categories of medical materials, and showed that price differences still existed for all these items. However, the number of items investigated was small for each category, and generalization of the results might have been limited. The present study conducted a further investigation into price information for multiple items for each category, focusing on 5 cardiovascular devices. METHODS: The US market price information was obtained from interviews of a healthcare provider network and 2 different group-purchasing organizations. We could obtain price information on 19 items in 5 categories. We substituted the Japanese reimbursement prices for the Japanese market prices. RESULTS: The price ratio (Japanese reimbursement price / US market price)was 2.0-3.5 for coronary stents, 5.9-6.8 for percutaneous transluminal coronary angioplasty catheters, 2.2-3.5 for pacemakers, 1.6-2.5 for mechanical valves, and 3.4-4.7 for oxygenators. CONCLUSIONS: The price disparities for cardiovascular devices between Japan and the US were reconfirmed. Japan's healthcare system should establish group-purchasing organizations, promote centers of clinical excellence, and abolish regulation of parallel imports and protectionism under the Japanese Pharmaceutical Affairs Law. PMID- 17354583 TI - Sequential use of aminophylline and theophylline for the treatment of atropine resistant bradycardia after spinal cord injury: a case report. AB - A 66-year-old Japanese man was brought to our emergency department after he was accidentally compressed into a lateral groove. Physical examination revealed pinprick sensory level of T4 and motor level of C7. On the 4th hospital day, electrocardiography suddenly showed sinus bradycardia of 33 beats/min. Bolus injection of 0.5 mg of atropine sulphate was not effective. Bolus injection of aminophylline was administered followed by continuous infusion. His heart rate increased and remained stable at 60 to 70 beats/min. Therapy was switched from aminophylline to oral theophylline and continued for about 5 weeks, with no recurrence of bradycardia. Use of xanthine derivatives is thought to be an effective, safe and simple treatment for spinal cord injury-induced bradycardia. PMID- 17354582 TI - [Potential risk caused by the lack of recognition of coronary spasm: analysis of the coronary spasm questionnaire in Japan]. AB - BACKGROUND: The spasm provocation test (SPT)is no longer widely used in patients with undiagnosed chest pain syndromes in the USA and Europe. Objectives. The clinical significance of the SPT was examined in Japan and compared with the frequency of coronary spastic angina (CSA) in institutions with and without SPT screening. METHODS AND RESULTS: Questionnaires concerning the number of cases of coronary angiography (CAG), percutaneous coronary intervention (PCI), and invasive/non-invasive SPT in 2005 were sent to members of the Japanese Circulation Society in 1,177 cardiology hospitals. Completed surveys were returned from 208 hospitals (17.7%). Non-invasive SPT was performed in only 27 hospitals (13.0%). Invasive SPT was not performed in 50 (24.0%) institutions, and performed in the remaining 158 institutions(< 10 cases/year: 29.8%, > or = 10< 50: 33.7%, > or = 50< 100: 8.7%, > or = 100: 3.8%). There was a close correlation between the number of acetylcholine/ergonovine SPTs and the number of CSA cases finally diagnosed (acetylcholine: r(2)= 0.907, ergonovine: r(2) = 0.76). There was no difference in the number/year of CAG (525+/-451 vs 513 +/-888, NS) and PCI(175+/-156 vs 144+/-225, NS) between institutions with and without SPT screening. However, the number of CSA cases (15.6+/-21.6 vs 4.2 +/-13.0, p < 0.01) and variant angina cases (3.3+/-7.2 vs 1.4+/-2.4)in hospitals with SPT screening was higher than hospitals without SPT screening. CONCLUSIONS: If Japanese cardiologists discontinue use of the SPT as in the USA and Europe, occurrence of CSA may disappear in the near future in Japan. PMID- 17354584 TI - [Survivor of blow out type of free wall rupture: multislice computed tomographic detection of myocardial rupture in a case of small myocardial infarction]. AB - A 73-year-old man was admitted to the emergency room because of shock and loss of consciousness. Electrocardiography and echocardiography revealed myocardial infarction of the inferoposterior wall and cardiac tamponade. However, laboratory data showed mild inflammation without elevation of any cardiac enzymes. Under percutaneous cardiopulmonary support, coronary angiography showed stenosis of only a small posterior descending branch of the right coronary artery. Multislice computed tomography provided a definite diagnosis of free wall rupture of the left ventricle, clearly showing the tear of the inferior wall. After surgical repair and rehabilitation, he returned to a normal life. Small inferior wall infarction rarely causes the blow out type of left ventricular free wall rupture. Multislice computed tomography is a fast and noninvasive tool for the detection of ventricular rupture as well as acute dissection of ascending aorta, both of which may result in cardiac tamponade and may not be visualized by echocardiography. PMID- 17354585 TI - [Unknown fever in a patient with implanted intracardiac lead]. PMID- 17354586 TI - Takotsubo cardiomyopathy represents a stress-induced myocardial stunning. PMID- 17354587 TI - [Mumps--a reemerging infection? The current incidence of mumps in the East Bohemian region in the Czech Republic]. AB - A review of mumps outbreaks among both non-vaccinated and vaccinated children and young adults in the East Bohemian region in 2003-2005 is presented. A significant increase in mumps cases was observed over this period. The clinical diagnosis was confirmed serologically by ELISA detection of IgM antibodies and/or IgG seroconversion and increased levels of IgG antibodies. A reverse transcriptase nested PCR was introduced for direct detection of mumps virus RNA from clinical specimens (nasopharyngeal secretion, saliva, CSF and serum). The isolated RNA will be stored for further analysis and mumps virus genotyping attempts, helpful in tracing the virus circulation in the East Bohemia region. Possible causes of the recent significant increase in mumps cases among the vaccinated population in the Czech Republic are discussed. PMID- 17354588 TI - [Prevalence of hepatitis G virus infection (HGV) in intravenous immunoglobulin recipients in the Czech Republic]. AB - The prevalence of hepatitis G virus (HGV) in the serum of intravenous immunoglobulin (IVIG) recipients was studied and risk related to HGV positivity was considered. Although its pathogenicity is unclear, HGV is likely to cause liver disease or lymphoproliferation. Twenty (23%) of 86 tested MG patients were HGV RNA positive. Of the HGV positive patients, three (15%) showed mild elevation of liver enzymes and one (5%) was diagnosed with chronic lymphatic leukaemia prior to the institution of MG replacement. It can be concluded that the HGV prevalence among IVIG recipients is high but is not associated with signs of either liver disease or lymphoproliferation. PMID- 17354589 TI - [Molecular epidemiology of invasive meningococcal disease in the Czech Republic]. AB - The study objective is to present results of clonal analysis of Neisseria meningitidis isolates from invasive meningococcal disease in the Czech Republic in 1993-2005. The method of multilocus sequence typing (MLST) revealed genetic heterogeneity of serogroup B isolates and homogeneity of serogroup C isolates. Three clonal sequence type complexes (STC-18, STC-32 and STC-41/44) prevailed among serogroup B isolates and almost a quarter of isolates have ST unclassifiable into clonal complexes. STC-11 showed clear predominance among serogroup C isolates. Hypervirulent clonal complex STC-11 prevailed in 1993-2004 while another clonal complex, STC-41/44, became more widespread for the first time in 2005. MLST analysis showed differences between the meningococcal population in the Czech Republic and those in western European countries and elsewhere. The results of clonal analysis of Neisseria meningitidis isolates from invasive meningococcal disease provide background information for evaluation of the adequacy of recommended measures in the focus of the disease and for updating the recommended vaccination strategy in the Czech Republic. PMID- 17354590 TI - [Nontuberculous mycobacteria and incidence of mycobacterioses in Prague in 1999 2004]. AB - OBJECTIVE: To analyze the incidence of nontuberculous mycobacteria detected in Prague patients in 1999-2004 as either single findings suggestive of clinical insignificance or repetitive findings suggestive of mycobacteriosis when reported together with the corresponding organ damage and symptomatology. MATERIAL AND METHODS: Nontuberculous mycobacteria were isolated and identified according to the Czech recommended methods for mycobacterial diagnosis in two Prague laboratories. The determined incidence rates of Mycobacterium (M.) kansasii, M. avium complex (MAC) and M. xenopi were compared with the respective nationwide rates and those of other nontuberculous bacteria, M. tuberculosis and M. bovis. The data on cases of mycobacterioses reported within the Czech Registry of Tuberculosis were provided by the Institute of Health Information and Statistics of the Czech Republic. RESULTS: In 1999-2004, the annual incidence rates of nontuberculous mycobacteria detected in Prague patients ranged between 169-139 and accounted for 13-25% of the totals of isolated mycobacteria including M. tuberculosis and M. bovis. Over this period, M. kansasii, MAC and M. xenopi were detected in 45, 76 and 43 patients, respectively. The single to repetitive detection ratio was the highest for M. kansasii (1:1.6), followed by MAC (1:1.8) and M. xenopi (1:2.3). Most male excretors were from higher age categories (median of 58-73 years) while the median age of female excretors ranged between 41 and 75 years. As many as 47 cases of mycobacterioses caused by the following agents: M. kansasii (20 cases), MAC (17 cases), M. xenopi (6 cases) and other nontuberculous mycobacteria (4 cases), were reported to the National Registry of Tuberculosis over the study period. CONCLUSIONS: Detection and identification of nontuberculous mycobacteria have become part of diagnostic routine of mycobacteriological laboratories. Compared to conventional tuberculous mycobacteria, detection of nontuberculous mycobacteria often requires the use of different and more cumbersome procedures such as incubation at preferential temperatures, longer incubation for detection of growth in primary cultures, species specific culture media, etc.. More skills and experience are needed for the use of automated detection systems and molecular biological techniques for species identification and interpretation of results. Regular consultations with clinical and outpatient physicians are crucial for the assessment of pathogenetic potential of nontuberculous mycobacteria. PMID- 17354591 TI - [Comments on antiphospholipid antibody tests]. AB - The Lancet was the first to report the use of anticardiolipin antibody test in a group of patients at risk of recurrent arterial and/or venous thrombosis and recurrent pregnancy losses, 23 years ago. The condition characterized by specific clinical and laboratory signs and initially called the anticardiolipin syndrome came to be known as the antiphospholipid syndrome (APS) when cross-reactivity of cardiolipin with other phospholipids was revealed. The study of APS still arouses controversy. Even after two decades of research, there is disagreement on the standardisation and interpretation of antiphospholipid antibody (APLA) test results. More international workshops have been organized on APLA tests than on any other autoantibody test. However, there is still wide interlaboratory variation in APLA detection. Therefore, comprehensive quality control procedures have to be integrated into the routine workload of laboratories performing APLA analysis. Participation in an external quality assessment (EQA) scheme is essential for any laboratory seeking to maintain and provide quality service. PMID- 17354592 TI - [Microbiology online--interactive learning and a new discussion forum for microbiology teachers]. AB - Rapid development of multiple disciplines of science, increasing numbers of university students and the advent of new learning technologies (e-learning, teleconferences, etc.) have drawn increasing interest in the contents, rationale and forms of learning. New Websites with a discussion forum for microbiology teachers have been available on the Web. In brief, the credo of this project called Forum is: "Teachers can learn from each other". The project is accessible free of charge at www.medmicro.info. Another source intended for free use by both teachers and students is "Learning pages of the Institute of Microbiology, Faculty of Medicine, Masaryk University" with the following sections: encyclopaedia, guidance on practical exercises, video clips and on-line laboratory using web cameras. The learning pages are available in both Czech and English. PMID- 17354593 TI - [East Side Story or an epidemiologist in the former USSR]. PMID- 17354594 TI - [Contemporary scientific problems of railway hygiene]. AB - The authors present contemporary scientific problems of railway hygiene, their solutions and prospects, as well as research trends in solving the same problems of other means of transport. PMID- 17354595 TI - [Maritime medical service as a means to preserve health in water transport workers]. AB - The authors justify new views of maritime medical service as a science of work ecology for individuals engaged into high risk occupations. The article describes unfavorable factors experienced by seamen during long voyages, presents analysis of maritime medicine state in Russia and outlines prospects for development of such medical branch. PMID- 17354596 TI - [The changes of pilot's cardianc rhythm indices and components of his operator's activity during modelling flight situations]. AB - The changes of pilot's cardiac rhythm and components of his operator's activity were investigated on the flight simulator under the conditions of modelling the fly over landing with the different centres causing the level of pilot's load. Under such conditions the heart rate was connected mainly with the subjective assessment of his operator's and psychological comfort by the pilot himself an d cardiac rhythm variability was connected with the level of operator's comfort during controlling flight parameters. PMID- 17354597 TI - [Arterial hypertension and risk factors in automobile drivers of Far North]. AB - The authors revealed peculiarities of arterial hypertension in automobile drivers working in Far North and subjected to variety of occupational hazards, so this disease could be considered occupational entity. Facts show that work conditions of automobile drivers in Far North deteriorate course of arterial hypertension and increase importance of risk factors in its prevalence. PMID- 17354598 TI - [Influence of optotypes' contrast changes on visual acuity in automobile drivers]. AB - When optotypes' contrast changes, one can see reliable difference with optotypes presentation on gray and dark gray background. Light gray background does not influence visual functions, there was no reliable difference. Authors point out possible forecasting of visual acuity decrease with optotypes' contrast changes- that is extremely important for occupational selection of automobile drivers, as dark gray background is major in dusty rainy weather when objects and traffic signs are hardly distinguishable. PMID- 17354599 TI - [Gastric and duodenal peptic ulcer in automobile drivers: prevalence, clinical features and prophylaxis]. AB - The authors first studied epidemiology of gastric and duodenal peptic ulcer, risk factors of gastro-duodenal diseases among automobile drivers; defined their real frequency and clinical features--presence of intensive boundary psychic disorders, combination with arterial hypertension and coronary heart disease, lower quality of occupational efficiency. PMID- 17354600 TI - [Approaches to lower occurrence of chronic bronchitis in railway workers subjected to occupational risk of respiratory diseases]. AB - The article deals with analysis of peculiarities in morbidity and social importance of chronic bronchitis as a leading nosologic entity among railway workers whose work is associated with constant exposure to risk factors of respiratory diseases. The authors compare clinical efficiency of various schemes concerning treatment of chronic bronchitis and the relapses prevention. PMID- 17354601 TI - [Influence of diuretics on occupationally important qualities of engine drivers]. AB - The authors studied influence of diuretics (Hypothiazide, Brinaldix, Triampur, Verospiron) on psychophysiologic occupationally important features of 44 engine drivers suffering from arterial hypertension stage I and II. Findings are that Hypothiazide and Verospiron suppress psychophysiologic occupationally important features. Triampur and Brinaldix have no negative influence on these functions and could be recommended for supportive (at workplace) antihypertensive therapy. PMID- 17354602 TI - [Methods of diagnostics and differentiation of the plague agent: intraspecies differentiation of Yersinia pestis. Part II]. AB - State Research Institute for Plague Control, Rostov-on-Don In the second part of the review aspects of intraspecies differentiation of the plague agent are discussed. Special emphasis is placed on the necessity of more precise definition of taxonomic position of plague agent isolates considering genotypical characteristics, data on their selective virulence, and evolutionary origin of the genus Yersinia. PMID- 17354603 TI - [Molecular genetic methods of typing of the Bartonellae]. AB - The primer systems for the PCR detection of four house-keeping genes of bartonellae in clinical material were developed and tested. The tactics of the species RFLP typing was also developed and tested. The scheme of the species RFLP typing of bartonellae was tested using as an example two strains for the first time isolated in Russia from patients with endocarditis and fever of uncertain origin. The results of the typing were supported by sequencing of the amplicons obtained. According to the sequencing the isolates were attributed to the sub species Bartonella vinsonii, subsp. arupensis. The necessity of molecular epidemiological analysis of bartonelloses in Russia was substantiated. PMID- 17354604 TI - [A study of the prevalence of regulatory genes controlling virulence gene expression among Vibrio choleraeeltor biovariant strains varying in their pandemic potential]. AB - The evolution of the genome of the pathogenic agent of the seventh cholera pandemia Vibrio cholerae eltor biovariant was thought to occur by acquiring not only structural genes of virulence but also regulatory systems as a result of horizontal transfer events. The polymerase chain reaction revealed the presence of the following regulatory genes that control the virulence gene expression in the chromosome of pre-pandemic and pandemic strains of cholera vibrios eltor: toxR, toxT, tcpP, tcpH, luxS, luxO, crp, vicH, pepA. The avirulent V. cholerae strain ATCC14033 isolated in 1910 (hypothetical predecessor of the cholera eltor agent) was shown to be lacking the regulatory genes toxT, tcpP, tcpHlocalized in the pathogenicity island VPI-1, and to be capable of realizing positive control over the expression of the virulence genes involved in the ToxR regulon. The virulent strains isolated from cholera patients during the local cholera outbreak in Indonesia in 1937 did not differ from the strains that caused cholera eltor pandemic in 1961. The strains had identical content of the regulatory genes tested. Only one strain of the four isolates studied contained no tcpPgene. Two key regulatory genes, toxR and toxT, were sequenced in all the isolates. The toxR nucleotide sequence of three pre-pandemic strains was shown to be indistinguishable from that of the pandemic isolates. On the other hand, the clinical strain MAK757 isolated prior to the emergence of the epidemic demonstrated an altered nucleotide sequence in its toxR gene. Experiments with the intra-intestinal challenge of suckling rabbits were indicative of similar virulence levels for the pre-pandemic and pandemic clinical strains. These results may serve as the evidence of the in vivo activity of the pre-pandemic strains of the toxT, tcpH, and tcpP positive regulatory genes that acquired in V. cholerae during the evolutionary process. PMID- 17354605 TI - [Point mutations in tox promoter/operator and diphtheria toxin repressor (DTXR) gene associated with the level of toxin production by Corynebacterium diphtheriae strains isolated in Belarus]. AB - DNA fragments 129 bp in length containing promoter region of the tox gene from 81 toxigenic strains Corynebacterium diphtheriae were analyzed using the SSCP (single strand conformational polymorphism). We found that only two strains had mutations; the strains also had highest levels of toxin production (over 5120 Vero CD50/ml). Other strains were characterized either as high-level toxin producing (640-5120 Vero CD50/ml, 41 strains) or low-level toxin-producing (40 320 Vero CD50/ml, 38 strains). Nucleotide sequence analysis revealed single T to C mutations at positions -54 and -184 within -232 - +85 region of tox operon. The first mutation at the -184 position was mapped outside the tox promoter/operator, whereas the second substitution at the -54 position modified the 9-base-pair interrupted palindromic sequence of the tox promoter/operator from ATAATTAGG in the wild-type bacteriophage (to ACAATTAGG in strains with enhanced level of toxin production. Nucleotide sequence analysis of -76 - +681 region of diphtheria toxin repressor (dtxR) gene from 15 strains of C. diphtheriae revealed two missense mutations resulting in amino acid substitutions A 147 V; and L 214 I in the C terminal region of the DtxR protein. Seven of these strains were identified as high-level toxin-producing and 4 strains, as low-level toxin-producing. In addition, one low-level toxin-producing strain was shown to contain a missense mutation leading to amino acid substitution I 221 T. Three strains, including two highest-level toxin producing strains contained no nucleotide substitutions, as well as the C7(-) strain. The 10 strains belonging to the Sankt-Peterburg and Rossija epidemic ribotypes as well as NCTC 13129 strain (etiologic agent of the diphtheria epidemic outbreak in the Eastern Europe) was shown to contain two mutations A 147 V and L 214 I in the C-terminal region of the DtxR protein. PMID- 17354606 TI - [Cloning and expression of the IGA-specific endopeptidase genes from Neisseria meningitidis]. AB - IgA1-specific proteinases (Igase) are acknowledged as a pivotal pathogenicity factor in meningococcus (Neisseria meningitidis) and in some related bacteria. These enzymes belong to trypsin-like clan of serine proteases. They exhibit high substrate selectivity being able to discriminate between IgA1 and IgA2. On the other hand, these enzymes are able to distinguish the human IgA1 from IgA1 of non primate species of mammals. In addition to conventional IgA1-processing enzymes, alternative enzymes were recently reported to occur in meningococci. However, the substrate specificity of the conventional Igase, its role in pathogenesis, and ability to complement functionality remains obscure. Within the framework of the present project we studied the structure of the Igase genes and their products in two highly virulent N. meningitidis serogroup A strains M9 and A208. In particular, we succeeded to find both conventional and alternative Igase genes in each genome: nucleotide sequences of these genes were deposited in the NCBI Gene Bank under the access number AY770504, AY558158, AY558159. The DNA sequence of the conventional Igase was almost entirely conserved in the two strains, whereas the recently discovered alternative Igase (formerly known as meningococcal adhesine, type 1) exhibited occurrence of a variable region spanning about 900 bp in the 5'-terminal part of the gene. Conventional genes from both strains were expressed in E. coli rendering inclusion bodies. The recombinant products were used for immunization of rabbits and exhibited reaction with both recombinant and native antigen from the N. meningitidis cultural medium. PMID- 17354607 TI - [Experimental evaluation of the biological risks of introduction of the genetically modified microorganism (GMM) B. subtilis VKPM B-7092 into the environment]. AB - Experimental evaluation of the biological risks of introducing the genetically modified microorganism (GMM) B. subtilis VKPM B-7092, an active ingredient of the probiotic VETOM 1.1, into an open system was performed. The following features of the GMM were studied: the survival rate of the GMM in bovine gastroenteric tract; its influence on the microbiocenosis; the species composition of microflora of the gastroenteric tract of the animal species; the possibility of transfer of the DNA fragment cloned in the B. subtilis bacterium and containing the gene of human leukocyte alpha2 interferon to the representatives of intestinal microflora of animals fed on the probiotic VETOM 1.1, as well as the GMM transfer to other microorganism species spread in the areas of potential getting of the GMM into the environment (soil). The study revealed no negative effects of the GMM on the animal organism and the environment, including remote aftereffects. PMID- 17354608 TI - The effects of linking substituents on the in vivo behavior of site-directed, peptide-based, diagnostic radiopharmaceuticals. AB - A number of human cancers are known to over-express the gastrin-releasing peptide receptor (GRPr) on cell surfaces. The high specificity and affinity of bombesin (BBN), an amphibian analogue of mammalian gastrin-releasing peptide, for the GRPr makes it an ideal candidate for delivery of diagnostic probes, such as 99mTc radiometal, to tumor sites. An optimized targeting agent possesses high tumor uptake with minimal uptake in normal tissues. In this study, 99mTc-targeting vectors of bombesin using various amino acid/aliphatic pharmacokinetic modifiers or linking groups were evaluated to determine the effect of the spacer on receptor binding affinity, internalization/externalization and biodistribution. Conjugates of the general type [DPR-X-BBN] (X = amino acid/aliphatic pharmacokinetic modifier) were synthesized by solid phase peptide synthesis (SPPS) and metallated with either low-valent, radioactive Tc-99m(I) or non radioactive Re(I)-tricarbonyl precursors. All of the new non-metallated and metallated conjugates were characterized by electrospray ionization mass spectrometry (ESI-MS). Receptor binding affinity, internalization/externalization and biodistribution studies in normal (CF-1) and tumor (human prostate PC-3 bearing mice) are reported. The effectiveness of targeting xenografted PC-3 tumors in rodents for two of the new 99mTc-BBN conjugates is demonstrated herein using small animal single photon emission computed tomography (SPECT). PMID- 17354609 TI - Minimal size MIDGE vectors improve transgene expression in vivo. AB - Viral and plasmid vectors may cause immunological side-effects resulting from the expression of therapeutically unwanted genes and from CpG motifs contained in their sequence. A new vector type for minimalistic, immunological-defined gene expression (MIDGE) may overcome these problems. MIDGE is a minimal size gene transfer unit consisting of the expression cassette, including promotor, gene and RNA-stabilizing sequences, flanked by two short hairpin oligonucleotide sequences. DNA not encoding the desired gene is reduced to a minimum. To compare transfection efficiencies in vivo hydrodynamics-based, systemic transfection was performed in BALB/c mice with MIDGE vectors and corresponding plasmids. The transfection efficiencies of the MIDGE vectors as measured by luciferase expression were significantly higher in liver (2.5-fold), lung (3.5-fold), kidneys (3.9-fold) and heart (17-fold) as compared to plasmids. The mean numbers of MIDGE vector molecules per cell as measured by quantitative PCR were also significantly higher. These advantages suggest the preferential use of this new vector type for clinical gene therapy studies. PMID- 17354610 TI - Regulation of Candida albicans morphogenesis by tumor necrosis factor-alpha and potential for treatment of oral candidiasis. AB - BACKGROUND: Endogenous tumor necrosis factor-alpha (TNF-alpha) has a beneficial effect as an activation mediator of host defense against infection by the fungus Candida albicans (C. albicans). However, it is unclear whether exogenous TNF alpha has a beneficial or detrimental effect against Candida. MATERIALS AND METHODS: The direct effect of TNF-alpha on CO2-induced morphological transformation of C. albicans blastoconidia was examined in vitro and the effect of TNF-alpha was determined in a mouse model of oral candidiasis. RESULTS: TNF alpha suppressed hyphal formation from C. albicans blastoconidia directly and dose-dependently, whereas it did not affect the fungal budding rate at concentrations ranging from 0.01 to 10 microg/ml. In vivo, the oral administration of TNF-alpha significantly reduced the C. albicans CFU in tongue tissues of treated mice. Histopathologically, there was a decrease in the number and size of C. albicans fungi in the tongue tissues. CONCLUSION: Since orally administered TNF-alpha suppressed fungal burden in the tongue tissue without significant detrimental effects, TNF-alpha has potential as a therapeutic agent against Candida. PMID- 17354611 TI - Correlation between duration of courtship and litter size in outbred NMRI mice. AB - When group-housed female mice are exposed to male mice, male pheromones induce female ovarian cyclicity resulting in a majority of the females entering estrus and spontaneous ovulation on the third night following introduction of the male- the so-called Whitten effect. We previously demonstrated that females mating on the third night after being housed with a male mouse ovulated significantly more eggs than did females mated on the first, second and fourth night, and that this effect was mediated by follicle stimulating hormone (FSH). The present study demonstrated that female mice, which were mated early after being housed with a male mouse (1-2 days), delivered significantly smaller litters than did females mated after spending 3-4 days with the male prior to mating. The implications both from practical animal production perspective, as well as from a fundamental biological perspective may be significant. In addition, the findings may have a practical research value making scientists in reproductive research aware of the natural variation in litter size, which may be an important confounding variable in all research in which litter size is a variable or a parameter used as a measure of the impact of an experimental treatment. PMID- 17354612 TI - Cyclooxygenase-2 (COX-2) expression in human endometrial carcinoma and precursor lesions and its possible use in cancer chemoprevention and therapy. AB - In recent years, the design of new antineoplastic agents that can halt the progression of human malignancies with minimal systemic damage has been at the forefront of cancer research, with cyclooxygenase-2 (COX-2) as a major target molecule. With an aim to demonstrate the expression and role of COX-2, the principal putative target of COX-2 inhibitor therapy, in endometrial adenocarcinoma (EACA) and precursor lesions, atypical complex hyperplasia (ACH) and endometrial hyperplasia (EH), an immunohistochemical (IHC) analysis of 22 primary human EACAs and 14 precursor lesions was carried out. Relevant clinicopathological data were tabulated from a random computer-generated sample of 22 primary EACA patients, treated by hysterectomy at our institution. Representative tumor sections including adjacent precursor lesions and normal endometrium (NE) were immunostained with human monoclonal anti-COX-2. Qualitative and semi-quantitative COX-2 IHC staining scores were determined based on the proportion of immunoreactive cells and the intensity of cytoplasmic COX-2 expression. Fisher's exact test and the Wilcoxon Rank Sum test were used for statistical analysis. Mean patient age was 68 years (range 51-93). All 22 EACAs were of endometrioid type, of which ten (45%) were grade I, eight (36%) grade II and four (18%) were grade III. Overall, four out of nine (44%) EHs, four out of five (80%) ACHs, and 18 out of 22 (88%) EACAs were COX-2 positive. The mean COX-2 IHC scores for EH and EACAs were 33 (SD 24.11) and 76 (SD 54.57), respectively (p = 0.022). Strong or moderate COX-2 expression was observed in 17 out of 22 (77%) adenocarcinomas as compared to two out of 14 (14%) of the precursor lesions (EH and ACH). The areas of adenomyosis were COX-2 positive, while myometrial smooth muscle and normal fallopian tube tissues stained negative for COX-2. The demonstration of frequent and strong expression of COX-2 in human EACAs supports a possible role for COX-2 inhibitors. Furthermore, an increasing expression of COX-2 from EH to invasive EACAs suggests potential usefulness of COX-2 inhibition to halt the progression of precursor lesions to invasive endometrial cancers. PMID- 17354613 TI - The role of the insulin-like growth factor 1 (IGF-1) in skeletal muscle physiology. AB - The human insulin-like growth factor-1 (IGF-1) gene gives rise to multiple, heterogeneous mRNA transcripts through a combination of multiple transcription initiation sites, alternative splicing and different polyadenylation signals. These IGF-1 mRNA transcripts code different isoforms of the precursor peptide of IGF-1 (IGF-1Ea, IGF-1Eb and IGF-1Ec or MGF in human skeletal muscle), which also undergo post-translational modification. There is increasing interest in differential expression and implication of IGF-1 isoforms in the regulation of muscle fiber regeneration and hypertrophy following mechanical overloading and damage. The identification of a locally expressed, loading- or damage-sensitive IGF-1 isoform in skeletal muscle was one of the most attractive developments in the context of the autocrine/paracrine actions of IGF-1. The concept that the competing processes of cellular proliferation and differentiation and the increased protein synthesis required for muscle repair or hypertrophic adaptation are regulated by a differential expression and by distinct roles of IGF-1 isoforms is discussed in the present review. PMID- 17354614 TI - Comparison of immediate and delayed implantation using the square-threaded and resorbable-blasted-media-treated surface implant system. AB - A variety of dental implant systems are now available that optimize bone-to implant contact. The present study was performed to compare the outcomes, by measuring peri-implant osseointegration, following immediate and delayed insertion of square-threaded and resorbable-blasted-media (RBM)-treated surface implants in the dog's mandible. Three dogs were used and four implants were inserted in each dog. All implants were used for histological and histomorphometrical evaluations. The contact lengths and osseointegrated areas following immediate implantation were 74.99% and 56.08%, and those following delayed implantation were 78.22% and 66.08%, respectively. The implantation method in dogs using the square-threaded and RBM treated surface implant system achieved higher percentages of osseointegration than previously reported and the two implantation techniques did not differentially influence osseointegration. Thus, immediate implantation of this implant system, which minimizes the number of surgical procedures, is an optimal clinical method to replace extracted teeth in dogs. PMID- 17354615 TI - Wavelet analysis of the effects of static magnetic field on skin blood flowmotion: investigation using an in vivo rat model. AB - BACKGROUND: In the literature, various in vivo studies on animals have demonstrated that a static magnetic field (SMF) might maintain microvascular tone in the cutaneous microcirculatory system by its biphasic effects on vasomotion. Here, the effects of locally applied SMF on skin blood flowmotion within the stressed or unstressed skin in the trochanter area were evaluated using wavelet analysis of skin blood perfusion as measured by laser Doppler flowmetry (LDF) in anesthetized rats. MATERIALS AND METHODS: Forty-eight experimental trials were carried out on twelve Sprague-Dawley rats. Four experimental groups were formed at random: i) Group CNL (no loading or SMF exposure; n = 12 trials); ii) Group SMF (SMF exposure only; n = 12 trials); iii) Group L (stressed skin without SMF exposure; n = 12 trials); iv) Group L + SMF (stressed skin with SMF exposure; n = 12 trials). RESULTS: SMF significantly enhanced endothelial related metabolic activity (0.01-0.05 Hz) in the stressed skin (p = 0.03). However, SMF did not induce significant change in the flowmotion amplitude in the unstressed skin (p = 0.22). CONCLUSION: The modulating effect of SMF on skin blood flowmotion might be related to the vascular tone modified by prolonged loading. PMID- 17354616 TI - Implants of type I collagen gel containing MG-63 osteoblast-like cells can act as stable scaffolds stimulating the bone healing process at the sites of the surgically-produced segmental diaphyseal defects in male rabbits. AB - BACKGROUND: Three-dimensional (3-D) type I collagen gel culture systems allow long-term growth of osteoblast-like cells, in vitro. Whether the implantation of 3-D collagen systems can stimulate new bone formation was assessed in male rabbits. MATERIALS AND METHODS: A 10-mm segmental diaphyseal defect was surgically produced at the left and right limbs of 50 adult male rabbits. The 3-D systems containing MG-63 osteoblast-like cells were implanted at the right-limb defects of all 50 animals. Twenty-five left-limb defects were implanted with 3-D collagen gels containing no MG-63 cells, while the rest were left empty. The bone repair process was serially assessed by radiography for up to 8 weeks and by histological analysis for up to the week 32 post-surgery. RESULTS: Ninety-four per cent (94%) of the right-limb defects, presented radiographic evidence of complete bone-end bridging within 8 weeks. None of the 50 left-limb defects presented radiographic post-implantation evidence of bone-end bridging. The radiographic evidence of the bone-end bridging was corroborated with histological evidence of new bone formation, while the medullar canals were filled with bone marrow elements. CONCLUSION: Implants of the 3-D collagen gels containing osteoblast-like cells can be used as stable scaffolds allowing the migration/proliferation of the bone regenerating cells in male rabbits. PMID- 17354617 TI - Fatty acid composition of plasma and kidney in rats with anti-Thy1.1 nephritis. AB - BACKGROUND: n-3 Polyunsaturated fatty acids (PUFA) are reported to ameliorate atherosclerotic and inflammatory diseases because they compete with arachidonic acid and reduce its inflammatory metabolites. In the present study, the fatty acid composition of plasma and kidney in rats with anti-Thy1.1 nephritis was investigated. MATERIALS AND METHODS: A group of male Wister rats weighing about 200 g was injected with anti-Thy1.1 antibody (1.25 mL/kg) through their tail veins (nephritis group). Rats in the control group were injected with saline. Five days after the injection, urinary protein levels were determined. All rats were then sacrificed and fatty acid composition of plasma and kidney were analyzed. RESULTS: Eicosapentaenoic acids (EPA) levels in the kidney phospholipid (PL) fraction in the nephritis group were significantly lower than those in the control group (0.67 +/- 0.06 mol% vs. 0.96 +/- 0.06 mol%, p < 0.05). EPA levels in the plasma PL fraction in the nephritis group were also significantly lower than those in the control group (0.38 +/- 0.05 mol% vs. 0.59 +/- 0.03 mol%, p < 0.05). Urinary protein levels 5 days after the injection were inversely correlated with EPA levels in the kidney PL fraction (r2 = 0.65, p = 0.01). These results suggested that decreased EPA levels in the kidney PL fraction might play an important role in anti-Thy1.1 nephritis. PMID- 17354618 TI - Endotoxin augments hemodynamic and metabolic effects of formyl-methionyl-leucyl phenylalanine (FMLP) in rabbits. AB - The chemotactic factor formyl-methionyl-leucyl-phenylalanine (FMLP) when injected in rabbits causes dose-dependent transient hypotension, as well as neutropenia, thrombocytopenia and a decrease in systemic vascular resistance, as previously shown. Since both FMLP and endotoxin are elaborated at sites of infection by certain bacteria, whether they act in concert to produce shock was examined. Animals were pretreated with 380 microg/kg of E. coli endotoxin, 24 hours before the infusion of 10(-9) moles FMLP and were compared with animals pretreated only with saline and administered FMLP. Within 3 min after FMLP, endotoxin-pretreated animals developed a significant fall in MAP (p < 0.001) and neutrophils (p < 0.001) compared to controls. Statistically significant lactic acidemia, with reduced HCO(-)3 levels also developed in the endotoxin-pretreated group after FMLP injection. These results indicate that endotoxin apparently induces a prepared state, thus facilitating the hemodynamic and cellular effects of FMLP in this model. PMID- 17354619 TI - The effect of aspartame administration on oncogene and suppressor gene expressions. AB - BACKGROUND: Aspartame (L-phenylalanine N-L-alpha-aspartyl-1-methyl ester) is an artificial sweetener with widespread applications. Previously published results have shown that among rats receiving aspartame a significant increase of lymphoreticular neoplasms, brain tumours and transitional cell tumours occurred. The aim of our short-term experiment was to investigate the biological effect of aspartame consumption by determining the expressions of key oncogenes and a tumour suppressor gene. MATERIALS AND METHODS: After one week per os administration of various doses of aspartame to CBA/CA female mice, p53, c-myc, Ha-ras gene expression alterations were determined in individual organs. RESULTS: The results showed an increase in gene expressions concerning all the investigated genes especially in organs with a high proliferation rate: lymphoreticular organs, bone-marrow and kidney. CONCLUSION: Aspartame has a biological effect even at the recommended daily maximum dose. PMID- 17354620 TI - Comparison of pain quality descriptors in cancer patients with nociceptive and neuropathic pain. AB - BACKGROUND: The aim of this study was to explore the differences in the descriptors for neuropathic and nociceptive pain in cancer patients. PATIENTS AND METHODS: One hundred and eighty-six cancer patients who participated in the study completed the Greek version of the McGill Pain Questionnaire (G-MPQ) for the assessment of their pain quality. RESULTS: Significant differences were found between type of pain in all G-MPQ classes. Statistically significant associations were found between Present Pain Intensity and type of pain (p = 0.002). Multivariate logistic regression analyses showed that patients who selected the descriptors "pricking" and "annoying" were 2.64 times and 2.2 times, respectively, more likely to experience nociceptive rather than neuropathic pain (p = 0.020 and p = 0.015, respectively). Further analysis showed that sensory seemed to be the most significant indicator for type of pain (95%, CI: 0.911 0.974, p < 0.001). CONCLUSION: Sensory quality and some of pain descriptors may differentiate neuropathic from nociceptive pain in cancer patients. PMID- 17354621 TI - Detecting changes in quality of life and psychiatric symptomatology following an in-patient detoxification programme for alcohol-dependent individuals: the use of WHOQOL-100. AB - The present study examines quality of life (QoL) and psychiatric symptomatology prior to and upon completion of a 5-week in-patient detoxification programme with the aim to identify any changes produced following clinical intervention. A group of 46 alcohol-dependent individuals, who were consecutively admitted for detoxification in the Psychiatric Hospital of the University of Athens, were clinically-assessed at admission and just before discharge with DSM-IV, CIDI-WHO and with the Hamilton Depression and Anxiety Scales (HDRS, HARS) and the Global Assessment Scale (GAS) for depression, anxiety and overall functioning, respectively. In addition, the patients were invited to complete the World Health Organization Quality of Life WHOQOL-100 instrument. Differences between admission and discharge scores were examined using related sample t-tests. Correlations between the WHOQOL-100 scores and clinically-assessed symptomatology measures were performed. Regression analysis was conducted to investigate the correlation of clinical and socio-demographic variables with patient overall QoL. The results indicate that QoL scores increased at discharge in 16 out of the 24 WHOQOL-100 facets. In addition, patient-assessed status of health was significantly improved. Improvement was also observed in the symptomatology scales rated by the clinician, providing evidence for lower levels of depression, anxiety and a higher level of functioning. Moderate correlations were found between WHOQOL-100 domains and psychiatric symptomatology scales. Significant WHOQOL-100 gains at discharge and clinically-assessed improvement in the HDRS, HARS and GAS, provide evidence of the WHOQOL-100 instrument's sensitivity to changes in clinical condition. The WHOQOL-100 measurement may be suitable for detecting QoL deficits or therapeutic gains in alcohol-dependent patients and may prove useful to mental health professionals for treatment planning. PMID- 17354622 TI - Chlamydia trachomatis C-complex serovars are a risk factor for preterm birth. AB - BACKGROUND: Potential associations between current or previous C. trachomatis infections (general IgG and serovars) and spontaneous preterm birth (PTB) were examined and associations between C. trachomatis infections and previous fertility problems were explored. PATIENTS AND METHODS: At week 17, Chlamydia antigen, Chlamydia IgG, Chlamydia complex B, C and GF levels were measured. Spontaneous preterm birth (< 37 completed weeks gestation) was the primary outcome, and secondary outcomes included infertility treatment, subfertility and ectopic pregnancies. Crude and adjusted relative risks (RR) and odds ratios (OR) were estimated by logistic regression. RESULTS: C. trachomatis C-complex positivity was associated with spontaneous PTB [RR 2.6 (1.1-6.29)] and additionally with a prior history of subfertility [OR 4.4 [2.5-7.7]), infertility treatment [OR 7.2 (4.0-12.8)] and ectopic pregnancy [5.2 (2.2-12.4)]. CONCLUSION: A previous infection with C. trachomatis C-complex was associated with an increased risk for spontaneous PTB and may potentially contribute to subfertility, infertility and ectopic pregnancy. PMID- 17354623 TI - Bcl-2, bax and p53 expression in rectal adenocarcinoma. Correlation with classic pathologic prognostic factors and patients' outcome. AB - BACKGROUND: Bcl-2 oncoprotein inhibits apoptosis, whereas bax protein promotes apoptosis by enhancing cell susceptibility to apoptotic stimuli. This study examined the bcl-2, bax and p53 expression in rectal adenocarcinomas and their relationship with tumor prognosis. PATIENTS AND METHODS: Paraffin-embedded 4 microm tumor sections obtained from patients with rectal adenocarcinoma who underwent colectomy for therapeutic reasons, were analyzed with a standard streptavidin biotin peroxidase method, using polyclonal and monoclonal antibodies. Patients were followed up for 1.5-83 (mean +/- SD: 47.19 +/- 6.2) months. RESULTS: Positive immunoreactivity for bcl-2, bax and p53 was detected in 21 (37%), 28 (50%) and 45 (80%) tumors, respectively. Bax was co-expressed in 17 out of 21 bcl-2(+) cases, whereas p53 was co-expressed in 18 out of 21 bcl-2(+) and 17 out of 28 bax(+) cases. Loss of bax expression was associated with advanced stage and high grade tumors (p < 0.01). Local (n = 6) or distant (n = 5) tumor recurrence was established in 11 cases. All these cases were bax(+), bcl-2( ) and p53(+). Bax and p53 expressions were correlated with adverse outcome (p < 0.05) while bcl-2 presence did not influence survival. Bcl-2(-)/bax(+)/p53(+) cases showed lower survival than bax(+)/bcl-2(+)/p53(+) cases (p < 0.001). CONCLUSION: In rectal adenocarcinoma, bax and bcl-2 proteins co-express frequently with p53. Co-expression of bax with p53 protein is associated with poor clinical outcome, especially in cases without concomitant expression of bcl 2. PMID- 17354624 TI - Immunohistochemistry and differential diagnosis of a solitary flat laryngeal xanthoma: a case report. AB - A 35-year-old woman presented with dyspnea, recurrent laryngitis and gastroesophageal reflux disease. Laryngoscopic examination revealed a yellow lesion on the anterior site of the left true vocal cord. No abnormal lesions were found in other portions of the larynx. The lesion was biopsied and a histological examination showed numerous foamy cells diffusely presented in the stroma of the specimen. Overlying squamous epithelium did not show cellular atypia. On the basis of histological appearance, the possible differential diagnosis included xanthomatous lesion, granular cell tumor or epithelial neoplasia. CD68, S-100 protein and cytokeratin immunoreactivities were investigated. Immuno histochemically, foamy cells were positive for CD68, indicating a histiocytic origin. PMID- 17354625 TI - Increased Bax/Bcl-2 ratio up-regulates caspase-3 and increases apoptosis in the thymus of patients with myasthenia gravis. AB - BACKGROUND: In this study the possible relation of Bax (an apoptosis promoter) to Bcl-2 (an apoptosis inhibitor) ratio with the apoptosis co-ordination enzyme, caspase-3, in the thymus of patients with myasthenia gravis (MG) was investigated in correlation with long-term clinical prognosis. PATIENTS AND METHODS: The study included 46 patients (17M/29F, mean age 36.60 +/- 16.09 yr) with MG, who underwent thymectomy for treatment. The clinical staging (Osserman classification) included: stage 1-5, IIA-21, IIB-17, III-3. The pathology of the thymus showed: hyperplasia-26, atrophy-8, thymoma B1 and B2 type-9, thymoma B3 type (well differentiated thymic carcinoma)-3. The patients were evaluated 39-166 (mean 91.87 +/- 38.38) months after thymectomy. At the end of the follow-up period, the patients were classified as follows: group A: complete stable remission, group B: pharmacological remission + minimal manifestations + improvement + deterioration. Paraffin sections of thymic tissue were subjected to: a) immunohistochemistry (bax, bcl-2, caspase-3 protein); b) in situ hybridization (bax, bcl-2 mRNA); and c) TUNEL-stain (apoptotic cells). Bax to bcl 2 mRNA and protein ratio was determined for each sample by dividing the % bax (+) cells by the % bcl-2 (+) cells. RESULTS: Follow-up data were available for 39/46 patients: 13/39 patients belonged to group A and 26/39 to group B. The Bax/Bcl-2 mRNA and protein ratios were increased towards advanced disease stages (+370% for mRNA and +391% for protein, from MG stage I to stage III). These ratios were correlated with caspase-3 expression (r = 0.782 and 0.583, p < 0.01) and apoptosis (r = 0.591 and 0.358 p < 0.01 and p < 0.05). All the 13 cases in group A had a Bax/Bcl-2 ratio < 1 (mean +/- SD: 0.58 +/- 0.04 for mRNA and 0.62 +/- 0.03 for protein), whereas all the 26 cases of group B had a ratio > 1 (1.47 +/- 0.07 for mRNA and 1.52 +/- 0.18 for protein). The Kaplan-Meier survival curve showed higher, free of disease, survival in group A (p = 0.0082). Cox regression analysis revealed that the Bax/Bcl-2 ratio was an independent prognostic factor, however the p-value was marginally significant (95% CI: 1.078-44.073, p = 0.041). CONCLUSION: This study has demonstrated that in patients with MG who underwent thymectomy: a) the Bax/Bcl-2 ratio may up-regulate caspase-3 expression and modulate apoptosis associated with progress of the disease; b) the Bax/Bcl-2 ratio < 1 was associated with complete stable remission after thymectomy; and c) Bax/Bcl-2 ratio was an independent predictive marker for therapeutic response after thymectomy. PMID- 17354626 TI - Report of two cases of endobronchial metastases secondary to colorectal cancer. AB - Two cases of endoluminar/endobronchial metastases (EEM) from a secondary extrathoracic tumour are reported. The patients, eight years after the curative treatment of colorectal adenocarcinoma, were examined exhibiting pulmonary symptoms with radiological findings in the chest and endobronchial lesions as an initial presentation. The use of fiberoptic bronchoscopy of endoluminar/endobronchial lesions may help in diagnosing the origin of metastatic spread in the presence or absence of a primary tumour. PMID- 17354627 TI - Divided nevus of the eyelids: three case studies. AB - Divided nevus or kissing nevus is a rare form of congenital nevus that usually occurs on adjacent parts of the upper and lower eyelids of one eye. Most often, the formation is present from birth, but it may also appear later. Three new cases during the period 1996 to 2004 are reported. Two of them were treated in our unit for oncological, functional and aesthetic purposes, and one preferred not to be operated on. All our patients had divided nevus of the left eyelid. In the first case, the reconstruction was achieved with two tarso-conjunctival flaps covered with skin grafts. In the second case, we used a technique based on autologous cultivated conjunctival epithelium. The third patient preferred not to be operated on and is still under clinical follow-up. Because of the severe disfigurement, risk of later malignant change in the lesion, and the possibility of deprivation amblyopia, early surgical treatment is very important. PMID- 17354628 TI - [The heart of women]. AB - Heart diseases in women have a very different incidence and prognosis from that of men. However, the selected diagnostic tools are very different in relation to gender. In a gender-related approach to atherosclerotic disease, one of the most important topic is the evaluation of risk to develop cardiovascular events in women. This review represents the opinion of a task force of the Italian Society of Cardiology, on all debated issues regarding the relationship between women and heart diseases. This working group has analyzed the literature published in the last years, integrating the concepts emerged from the experience of physicians accustomed to the study and treatment of women with heart diseases. First of all, we analyzed the epidemiology of coronary heart disease in women, emphasizing the differences in the risk of developing cardiovascular events between European and American women. Then, we illustrated the new risk factors for ischemic heart disease that have specifically been studied in large female populations. These new risk factors could be used for a better evaluation of the cardiovascular risk, and for analyzing gender differences in diagnosis, response to therapy and prognosis of atherosclerotic disease. Some considerations about postmenopausal hormone replacement therapy were done, by providing suggestions for a corrected diagnosis and therapeutic approach in women with known cardiovascular disease. Atherosclerosis represents a really different disease in females with respect to males. The analysis of the literature supports the hypothesis that the pathophysiological mechanisms of this disease may be different or peculiar according to gender. We therefore suggest a tailored approach to this disease, in order to better quantify global cardiovascular risk, treat and prevent cardiovascular diseases, with the aim to reduce cardiovascular mortality and morbidity. PMID- 17354629 TI - [Optical coherence tomography]. AB - Optical coherence tomography (OCT) is a recently developed technology capable of micron-scale imaging. Its high resolution (10-20 microm) makes intravascular OCT imaging the most interesting method for assessing atherosclerotic plaque microstructure in patients suffering from coronary artery disease. OCT allowed measurement of the thickness of the plaque fibrous cap, as well as identification of intima, media, and external elastic membrane in patients with normal coronary arteries. However, significant limitations still exist, including poor penetration in non-transparent tissue. The aim of this review is to give an update on OCT on the basis of the existing literature, with an overview of the strong and weak features of this technique. PMID- 17354630 TI - [Intermittent claudication in Italy. The Peripheral Arteriopathy and Cardiovascular Events (PACE) study]. AB - BACKGROUND: The epidemiology of intermittent claudication in the primary care settings has been studied almost exclusively in northern European and northern American populations. This article compares the results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study, the first survey in Italy to assess the prevalence, comorbidity and natural history of intermittent claudication, with those observed in other western countries. METHODS: From the lists of seven general practitioners, all patients aged 40-80 years (n = 4352) received a Rose questionnaire. In those reporting leg pain while leg pain while walking (n = 760), Doppler examination was performed. Intermittent claudication was defined as an ankle/branchial index of < 0.90, or reduced flow velocity. For each claudicant, three age- and sex-matched controls were randomly selected from patients negative to the questionnaire. RESULTS: The prevalence of both intermittent claudication (1.6%) and associated cardiovascular disease (34%) tended to be lower in Italy than in the United Kingdom, Netherlands, and North America. Conversely, no between country difference was observed with respect to mortality, which was very high (relative risk 4.08; 95% confidence interval 1.50 10.84, p = 0.006) in the PACE claudicants. CONCLUSIONS: In this regard it is noteworthy that these patients, who were managed almost exclusively by their general practitioner were undertreated with respect to the use of antiplatelet therapy and correction of risk factors. There is need to alert them to this topic. PMID- 17354631 TI - [Prominent Eustachian valve mimicking a right atrial mass]. AB - Eustachian valve, also called valvula venae cavae inferior, caval valve, sylvian valve, is an endocardial fold extending from the anterior margin of the inferior vena cava to the anterior part of the limbus fossa ovalis. In embryonic life it helps blood flowing through patent foramen ovale into the left atrium, thus shunting pulmonary circulation. After birth, Eustachian valve becomes an embryogenic remnant. Echocardiography is the standard tool to define correctly this membrane. Moreover, the literature reports some diagnostic pitfalls of this valve, mistaking interpreted as thrombus, vegetation or tumor. Right diagnosis of this membrane is necessary and clinically relevant in the rare cases of infective endocarditis or in the patent foramen ovale because sometimes a redundant valve interferes with Amplatzer PFO occluder placement. In this case report, we describe a prominent Eustachian valve previous interpreted as an endocardiac cyst. Integrated echocardiography (transthoracic, transesophageal and three dimensional reconstruction) defines correctly diagnosis, anatomy and kinesis of prominent Eustachian valve. PMID- 17354632 TI - [Aortic dolichoectasia]. PMID- 17354633 TI - [The management of echocardiography in Italy. Consensus Conference of the Italian Society of Cardiovascular Echography (SIEC)]. PMID- 17354634 TI - Volumetric quantification of atherosclerotic plaque in CT considering partial volume effect. AB - Coronary artery calcification (CAC) is quantified based on a computed tomography (CT) scan image. A calcified region is identified. Modified expectation maximization (MEM) of a statistical model for the calcified and background material is used to estimate the partial calcium content of the voxels. The algorithm limits the region over which MEM is performed. By using MEM, the statistical properties of the model are iteratively updated based on the calculated resultant calcium distribution from the previous iteration. The estimated statistical properties are used to generate a map of the partial calcium content in the calcified region. The volume of calcium in the calcified region is determined based on the map. The experimental results on a cardiac phantom, scanned 90 times using 15 different protocols, demonstrate that the proposed method is less sensitive to partial volume effect and noise, with average error of 9.5% (standard deviation (SD) of 5-7mm(3)) compared with 67% (SD of 3-20mm(3)) for conventional techniques. The high reproducibility of the proposed method for 35 patients, scanned twice using the same protocol at a minimum interval of 10 min, shows that the method provides 2-3 times lower interscan variation than conventional techniques. PMID- 17354635 TI - Alternating minimization algorithms for transmission tomography. AB - A family of alternating minimization algorithms for finding maximum-likelihood estimates of attenuation functions in transmission X-ray tomography is described. The model from which the algorithms are derived includes polyenergetic photon spectra, background events, and nonideal point spread functions. The maximum likelihood image reconstruction problem is reformulated as a double minimization of the I-divergence. A novel application of the convex decomposition lemma results in an alternating minimization algorithm that monotonically decreases the objective function. Each step of the minimization is in closed form. The family of algorithms includes variations that use ordered subset techniques for increasing the speed of convergence. Simulations demonstrate the ability to correct the cupping artifact due to beam hardening and the ability to reduce streaking artifacts that arise from beam hardening and background events. PMID- 17354636 TI - Pinhole SPECT with different data acquisition geometries: usefulness of unified projection operators in homogeneous coordinates. AB - To further improve pinhole single photon emission computed tomography (SPECT) imaging, there have been increasing interests in the use of nonstandard collimator designs and/or acquisition geometries. Homogeneous coordinates provide a compact and convenient framework to unify the geometric descriptions of the projection operators for these different imaging geometries, which may facilitate the implementation of iterative reconstruction algorithms and the investigation of crucial geometric calibration problems in pinhole SPECT. In this work, these advantages were demonstrated through three examples, namely, multipinhole SPECT, pinhole SPECT with a helical scanning orbit, and pinhole SPECT with dual detectors. Specifically, we showed adaptable implementations of iterative image reconstruction algorithms and translatable strategies for efficient geometric calibrations through unifying projection operators of the aforementioned imaging geometries. Notably, the unified geometric descriptions of multipinhole and single pinhole projection operators allowed us to derive that one can effectively calibrate a multipinhole geometry using only two point sources without measuring their distance. Experimental studies were performed to demonstrate the validity of our approaches, which may be extended to other pinhole SPECT and cone-beam X ray computed tomography imaging geometries. PMID- 17354637 TI - Vessel axis tracking using topology constrained surface evolution. AB - An approach to 3-D vessel axis tracking based on surface evolution is presented. The main idea is to guide the evolution of the surface by analyzing its skeleton topology during evolution, and imposing shape constraints on the topology. For example, the intermediate topology can be processed such that it represents a single vessel segment, a bifurcation, or a more complex vascular topology. The evolving surface is then reinitialized with the newly found topology. Reinitialization is a crucial step since it creates probing behavior of the evolving front, encourages the segmentation process to extract the vascular structure of interest and reduces the risk on leaking of the curve into the background. The method was evaluated in two computed tomography angiography applications: 1) extracting the internal carotid arteries including the region in which they traverse through the skull base, which is challenging due to the proximity of bone structures and overlap in intensity values; 2) extracting the carotid bifurcations including many cases in which they are severely stenosed and contain calcifications. The vessel axis was found in 90% (18/20 internal carotids in ten patients) and 70% (14/20 carotid bifurcations in a different set of ten patients) of the cases. PMID- 17354638 TI - Shear-based fast hierarchical backprojection for parallel-beam tomography. AB - We introduce a family of fast algorithms for 2-D parallel-beam tomographic backprojection. They aggregate the projections in a hierarchical structure involving the shearing and addition of sparsely sampled images. The algorithms achieve a computational cost of O(N(2) log P), when backprojecting an N x N pixel image from P projections. The algorithms provide a systematic means, guided by a Fourier-domain interpretation, to adjust and optimize the tradeoff between computational cost and accuracy. In an example with N = 512 and P = 1458 the algorithms provide high accuracy, with more than an order of magnitude reduction in operation counts. PMID- 17354639 TI - Fast predictions of variance images for fan-beam transmission tomography with quadratic regularization. AB - Accurate predictions of image variances can be useful for reconstruction algorithm analysis and for the design of regularization methods. Computing the predicted variance at every pixel using matrix-based approximations [1] is impractical. Even most recently adopted methods that are based on local discrete Fourier approximations are impractical since they would require a forward and backprojection and two fast Fourier transform (FFT) calculations for every pixel, particularly for shift-variant systems like fan-beam tomography. This paper describes new "analytical" approaches to predicting the approximate variance maps of 2-D images that are reconstructed by penalized-likelihood estimation with quadratic regularization in fan-beam geometries. The simplest of the proposed analytical approaches requires computation equivalent to one backprojection and some summations, so it is computationally practical even for the data sizes in X ray computed tomography (CT). Simulation results show that it gives accurate predictions of the variance maps. The parallel-beam geometry is a simple special case of the fan-beam analysis. The analysis is also applicable to 2-D positron emission tomography (PET). PMID- 17354640 TI - Iterative image reconstruction using inverse fourier rebinning for fully 3-D PET. AB - We describe a fast forward and back projector pair based on inverse Fourier rebinning for use in iterative image reconstruction for fully three-dimensional (3-D) positron emission tomography (PET). The projector pair is used as part of a factored system matrix that takes into account detector-pair response by using shift-variant sinogram blur kernels, thereby combining the computational advantages of Fourier rebinning with iterative reconstruction using accurate system models. The forward projector consists of a two-dimensional (2-D) projector, which maps 3-D images into 2-D direct sinograms, followed by exact inverse rebinning which maps the 2-D into fully 3-D sinograms. The back projector is implemented as the transpose of the forward projector and differs from the true exact rebinning operator in the sense that it does not require reprojection to compute missing line of responses (LORs). We compensate for two types of inaccuracies that arise in a cylindrical PET scanner when using inverse Fourier rebinning: 1) nonuniform radial sampling and 2) nonconstant oblique angles in the radial direction in a single oblique sinogram. We examine the effects of these corrections on sinogram accuracy and reconstructed image quality. We evaluate performance of the new projector pair for maximum a posteriori (MAP) reconstruction of simulated and in vivo data. The new projector results in only a small loss in resolution towards the edge of the field-of-view when compared to the fully 3-D geometric projector and requires an order of magnitude less computation. PMID- 17354641 TI - Nonparametric extraction of transient changes in neurotransmitter concentration from dynamic PET data. AB - We have developed a nonparametric approach to the analysis of dynamic positron emission tomography (PET) data for extracting temporal characteristics of the change in endogenous neurotransmitter concentration in the brain. An algebraic method based on singular value decomposition (SVD) was applied to simulated data under both rest (neurotransmitter at baseline) and activated (transient neurotransmitter release) conditions. The resulting signals are related to the integral of the change in free neurotransmitter concentration in the tissue. Therefore, a specially designed minimum mean-square error (MMSE) filter must be applied to the signals to recover the desired temporal pattern of neurotransmitter change. To test the method, we simulated sets of realistic time activity curves representing uptake of [11C]raclopride, a dopamine (DA) receptor antagonist, in brain regions, under baseline and dopamine-release conditions. Our tests considered two scenarios: 1) a spatially homogeneous pattern with all voxels in the activated state presenting an identical DA signal; 2) a spatially heterogeneous pattern in which different DA signals were contained in different families of voxels. In the first case, we demonstrated that the timing of a single DA peak can be accurately identified to within 1 min and that two distinct neurotransmitter peaks can be distinguished. In the second case, separate peaks of activation separated by as little as 5 min can be distinguished. A decrease in blood flow during activation could not account for our findings. We applied the method to human PET data acquired with [11C]raclopride in the presence of transiently elevated DA due to intravenous (IV) alcohol. Our results for an area of the nucleus accumbens-a region relevant to alcohol consumption-agreed with a model-based method for estimating the DA response. SVD-based analysis of dynamic PET data promises a completely noninvasive and model-independent technique for determining the dynamics of a neurotransmitter response to cognitive or pharmacological stimuli. Our results indicate that the method is robust enough for application to voxel-by-voxel data. PMID- 17354642 TI - Field inhomogeneity correction based on gridding reconstruction for magnetic resonance imaging. AB - Spatial variations of the main field give rise to artifacts in magnetic resonance images if disregarded in reconstruction. With non-Cartesian k-space sampling, they often lead to unacceptable blurring. Data from such acquisitions are usually reconstructed with gridding methods and optionally restored with various correction methods. Both types of methods essentially face the same basic problem of adequately approximating an exponential function to enable an efficient processing with fast Fourier transforms. Nevertheless, they have commonly addressed it differently so far. In the present work, a unified approach is pursued. The principle behind gridding methods is first generalized to nonequispaced sampling in both domains and then applied to field inhomogeneity correction. Three new algorithms, which are compatible with a direct conjugate phase and an iterative algebraic reconstruction, are derived in this way from a straightforward embedding of the data into a higher dimensional space. Their evaluation in simulations and phantom experiments with spiral k-space sampling shows that one of them promises to provide a favorable compromise between fidelity and complexity compared with existing algorithms. Moreover, it allows a simple choice of key parameters involved in approximating an exponential function and a balance between the accuracy of reconstruction and correction. PMID- 17354643 TI - Fast and accurate automatic registration for MR-guided procedures using active microcoils. AB - A fast, robust, accurate, and automatic registration technique based on magnetic resonance (MR) active microcoils (active markers) for registration of tracked medical devices to preprocedural MR-images is presented. This allows for a straight-forward integration of position measurement systems into clinical procedures. The presented method is useful for guidance purposes in clinical applications with high demands on accuracy and ease-of-use (e.g., neurosurgical or orthopedic applications). The determination of the positions of the active markers is integrated into the preparation phase of the actual MR imaging scan. The technique features a generic interface using DICOM standards for communication with navigation workstations linked to an MR system. The position of the active markers is fixed with respect to a reference system of an optical positioning measurement system (OPMS) and thus the coregistration of the MR system and the OPMS is established. In a phantom study, a mean overall targeting accuracy of 0.9+/-0.1 mm was achieved and compared favorably to results obtained from manual registration tests (1.8+/-0.3 mm) carried out in parallel. For a test person trained for both registration methods, workflow improvements of 3-6 min per registration step were found. The need for manual interaction is entirely eliminated thus avoiding user-bias, which is advantageous for the usage in clinical routine. The method improves the ease-of-use of tracking equipment during stereotactic guidance. The method is finally demonstrated in a volunteer study using a model of a Mayfield skull clamp with integrated active and optical reference markers. PMID- 17354644 TI - A system for real-time measurement of the brachial artery diameter in B-mode ultrasound images. AB - The measurement of the brachial artery diameter is frequently used in clinical studies for evaluating the flow-mediated dilation and, in conjunction with the blood pressure value, for assessing arterial stiffness. This paper presents a system for computing the brachial artery diameter in real-time by analyzing B mode ultrasound images. The method is based on a robust edge detection algorithm which is used to automatically locate the two walls of the vessel. The measure of the diameter is obtained with subpixel precision and with a temporal resolution of 25 samples/s, so that the small dilations induced by the cardiac cycle can also be retrieved. The algorithm is implemented on a standalone video processing board which acquires the analog video signal from the ultrasound equipment. Results are shown in real-time on a graphical user interface. The system was tested both on synthetic ultrasound images and in clinical studies of flow mediated dilation. Accuracy, robustness, and intra/inter observer variability of the method were evaluated. PMID- 17354645 TI - A review of methods for correction of intensity inhomogeneity in MRI. AB - Medical image acquisition devices provide a vast amount of anatomical and functional information, which facilitate and improve diagnosis and patient treatment, especially when supported by modern quantitative image analysis methods. However, modality specific image artifacts, such as the phenomena of intensity inhomogeneity in magnetic resonance images (MRI), are still prominent and can adversely affect quantitative image analysis. In this paper, numerous methods that have been developed to reduce or eliminate intensity inhomogeneities in MRI are reviewed. First, the methods are classified according to the inhomogeneity correction strategy. Next, different qualitative and quantitative evaluation approaches are reviewed. Third, 60 relevant publications are categorized according to several features and analyzed so as to reveal major trends, popularity, evaluation strategies and applications. Finally, key evaluation issues and future development of the inhomogeneity correction field, supported by the results of the analysis, are discussed. PMID- 17354646 TI - Fetal and perinatal mortality, United States, 2003. AB - OBJECTIVES: This report presents 2003 fetal and perinatal mortality data by a variety of characteristics, including maternal age, marital status, race, Hispanic origin, and state of residence; and by infant birthweight, gestational age, plurality, and sex. Trends in fetal and perinatal mortality are also examined. METHODS: Descriptive tabulations of data are presented and interpreted. RESULTS: The U.S. fetal mortality rate in 2003 was 6.23 fetal deaths of 20 weeks of gestation or more per 1,000 live births and fetal deaths. Fetal and perinatal mortality rates have declined slowly but steadily from 1990 to 2003. Fetal mortality rates for 28 weeks of gestation or more have declined substantially, whereas those for 20-27 weeks of gestation have not declined. Fetal mortality rates are higher for a number of groups, including non-Hispanic black women, teenagers, women aged 35 years and over, unmarried women, and multiple deliveries. Over one-half (51 percent) of fetal deaths of 20 weeks of gestation or more occurred between 20 and 27 weeks of gestation. PMID- 17354647 TI - Carbohydrate-binding agents: a potential future cornerstone for the chemotherapy of enveloped viruses? AB - Carbohydrate-binding agents (CBAs) inhibit HIV-1 and it is proposed that therapy with such agents may have important implications for the future of anti-HIV therapy. Examples of CBAs include the procaryotic cyanovirin-N (CV-N), plant lectins such as HHA, GNA, NPA, CA and UDA, the monoclonal antibody 2G12 directed against a glycan-containing epitope on HIV envelope gp120, and the mannose specific non-peptidic antibiotic Pradimicin A, which inhibits the entry of HIV-1 into its target cells. CBAs prevent not only virus infection of susceptible cells, but also inhibit syncytia formation between persistently HIV-infected cells and uninfected lymphocytes. In addition, CBAs may also prevent DC-SIGN mediated transmission of HIV to T-lymphocytes. Therefore, CBAs qualify as potential microbicide drugs. Long-term exposure of HIV to CBAs in cell culture results in the progressive deletion of N-glycans of HIV gpl20 in an attempt of the virus to escape drug pressure. In this respect, the CBAs are endowed with a high genetic barrier. Multiple mutations at N-glycosylation sites are required before pronounced phenotypic drug resistance development becomes evident. CBA treatment of HIV may consist of a novel chemotherapeutic concept with a dual mechanism of antiviral action: a direct antiviral activity by preventing HIV entry and transmission to its target cells, and an indirect antiviral activity by forcing HIV to delete glycans in its gpl20 envelope. The latter phenomenon will result in creating 'holes' in the protective glycan shield of the HIV envelope, whereby the immune system may become triggered to produce neutralizing antibodies against previously hidden immunogenic epitopes of gp120. If this concept can be proven in in vivo, low-molecular-weight non-peptidic CBAs such as Pradimycin A may become the cornerstone for the efficient treatment of infections of those viruses that require a glycosylated envelope (that is, HIV, but also hepatitis C virus) for entry into its target cells. In addition, influenza virus and coronavirus infections may also qualify to be treated by CBAs. PMID- 17354648 TI - High frequency of spontaneous helicase-primase inhibitor (BAY 57-1293) drug resistant variants in certain laboratory isolates of HSV-1. AB - Herpes simplex virus (HSV) helicase-primase is the target for a new group of potent antivirals that show great promise in vivo. A claimed advantage of this class of compounds is the low rate of drug resistance, which is reported to occur at a lesser rate than acyclovir (ACV)-resistance in cell culture. We confirmed that BAY 57-1293 is highly active against HSV-1 and superior to ACV when tested in Vero cells. Notably, drug resistance was detected in laboratory working stocks in two different strains of HSV at 10(-4) to 10(-5) and there was evidence that the resistant variants were present in the virus population before the selection was applied. Plaque-purified clones obtained from the parental viruses showed a lower level of resistance selection in the presence of drug (10-6) and this value is similar to published reports. In the case of HSV-1 SC16, no difference was observed between a working stock and a plaque-pure clone in the rate of resistance to the nucleoside analogue ACV. The working stocks were found to contain variants with resistance to BAY 57-1293 ranging from approximately 15 fold to 4,000-fold suggesting that these viruses have the potential to subvert effective therapy. Sequence analysis of HSV-1 helicase protein showed that most of the amino acid substitutions in the variants described in this study tallied with published results, with some interesting exceptions in the case of HSV-1 strain PDK. Resistant variants did not readily revert to a sensitive phenotype in the absence of the inhibitor and representative BAY 57-1293-resistant variants were cross-resistant to an alternative helicase-primase inhibitor, BILS 22 BS. Variants resistant to BAY 57-1293 retained sensitivity to the nucleoside analogue, ACV. PMID- 17354649 TI - Interaction of 2'-deoxyguanosine triphosphate analogue inhibitors of HIV reverse transcriptase with human mitochondrial DNA polymerase gamma. AB - Mitochondrial toxicity is a limiting factor in the use of some nucleoside reverse transcriptase inhibitors of HIV. To further understand the impact of structural features on the incorporation and exonuclease removal of nucleoside monophosphate (MP) analogues by human mitochondrial DNA polymerase (pol gamma), transient kinetic studies were done with analogues of 2'-deoxyguanosine triphosphate. The kinetic parameters for the incorporation and removal of carbovir (CBV)-MP, dioxolane guanosine (DXG)-MP and 2',3'-dideoxy-2',3'-didehydroguanosine (d4G)-MP were studied with pol gamma holoenzyme. The importance of the ribose oxygen in incorporation by pol gamma was illustrated by an approximate 3,000-fold decrease in the incorporation efficiency of an analogue lacking the ribose oxygen (CBV-TP) relative to those containing a ribose oxygen (DXG-TP and d4G-TP). As a result, a comparison with previous data for the incorporation by HIV reverse transcriptase showed CBV-TP to be approximately 800-8,000-fold more selective for its antiviral target over pol gamma relative to the other guanosine analogues. However, DXG-TP and d4G-TP were found to be much more selective than previously reported values for mitochondrial toxic nucleoside analogues. Structural modelling based on sequence homology with other polymerase A family members suggests that an interaction between the ribose oxygen and arginine 853 in pol gamma may play a critical role in causing this differential incorporation. Exonuclease removal of a chain-terminating CBV-MP was also found to be more efficient by pol gamma. These results help to further elucidate the structure activity relationships for pol gamma and should aid in the design of more selective antiviral agents. PMID- 17354650 TI - Superior efficacy of helicase-primase inhibitor BAY 57-1293 for herpes infection and latency in the guinea pig model of human genital herpes disease. AB - The efficacy of BAY 57-1293, a novel non-nucleosidic inhibitor of herpes simplex virus 1 and 2 (HSV-1 and HSV-2), bovine herpesvirus and pseudorabies virus, was studied in the guinea pig model of genital herpes in comparison with the licensed drug valaciclovir (Valtrex). Early therapy with BAY 57-1293 almost completely suppressed the symptoms of acute HSV-2 infection, and reduced virus shedding and viral load in the sacral dorsal root ganglia by up to three orders of magnitude, resulting in decreased latency and a greatly diminished frequency of subsequent recurrent episodes. In contrast, valaciclovir showed only moderate effects in this set of experiments. When treatment was initiated late during the course of disease after symptoms were apparent, that is, a setting closer to most clinical situations, the efficacy of therapy with BAY 57-1293 was even more pronounced. Compared with valaciclovir, BAY 57-1293 halved the time necessary for complete healing. Moreover, the onset of action was fast, so that only very few animals developed new lesions after treatment commenced. Finally, in a study addressing the treatment of recurrent disease in animals whose primary infection had remained untreated BAY 57-1293 was efficient in suppressing the episodes. In summary, superior potency and efficacy of BAY 57-1293 over standard treatment with valaciclovir was demonstrated in relevant animal models of human genital herpes disease in terms of abrogating an HSV infection, reducing latency and the frequency of subsequent recurrences. Furthermore, BAY 57-1293 shortens the time to healing even if initiation of therapy is delayed. PMID- 17354652 TI - [Didier Trono, dean of life sciences at the EPFL: "we want to give a twist to biomedical research"]. PMID- 17354651 TI - Antiviral profiles of novel iminocyclitol compounds against bovine viral diarrhea virus, West Nile virus, dengue virus and hepatitis B virus. AB - The antiviral activity of iminocyclitol compounds with a deoxynojirimycin (DNJ) head group and either a straight chain alkyl or alkylcycloalkyl group attached to the nitrogen atom have been tested in vitro against multiple-enveloped viruses. Several of these analogues were superior to previously reported DNJ compounds. Iminocyclitols that inhibit the glycan-processing enzyme endoplasmic-reticular glucosidase have been shown to inhibit the morphogenesis of viruses that bud from the endoplasmic reticulum (ER) at non-cytotoxic concentrations. Bovine viral diarrhoea virus (BVDV) has been used as a surrogate system for study of the hepatitis C virus, which belong to the virus family (Flaviviridae) as West Nile virus (WNV) and dengue virus (DV). N-Nonyl-DNJ (NNDNJ) was previously reported to have micromolar antiviral activity against BVDV, but a limiting toxicity profile. N-Butylcyclohexyl-DNJ (SP169) was shown to be as potent as NNDNJ in assays against BVDV and less toxic. However, it was inactive against hepatitis B virus (HBV). The present study reports efforts to improve the performance profiles of these compounds. Introduction of an oxygen atom into the N-alkyl side chain of DNJ, either as an ether or a hydroxyl functionality, reduced toxicity but sacrificed potency. Introduction of a hydroxyl group at the tertiary carbon junction of the cycloalkyl and linear alkyl group, as in N-pentyl-(1 hydroxycyclohexyl)-DNJ (OSL-9511), led to a structure that was as well tolerated as DNJ (CC50>500 microM), but retained micromolar antiviral activity against all ER morphogenesis budding viruses tested: BVDV, WNV, DV and HBV. The implication of this modification to the development of broad-spectrum antiviral agents is discussed. PMID- 17354654 TI - [Geriatrics]. AB - A new vaccine reduces the incidence and severity of zoster and its complications in older persons. A cost-effectiveness analysis highlights the implication of CDC's recent recommendation to vaccinate all persons aged 60 years and over. A meta-analysis confirms that the chronic use of sedatives in older persons provides modest benefits and important risks. Unfortunately, melatonin does not seem to be a useful alternative. A systematic review of interventions to prevent pressure ulcers provides scientific support to measures empirically used in most institutions. Finally, a randomized controlled trial questions the clinical benefit of atypical neuroleptics in Alzheimer's disease and a comprehensive review of pharmacological trials in mild cognitive impairment reports no benefit of any of the tested drugs on conversion rate to Alzheimer's disease. PMID- 17354653 TI - [Endocrinology]. AB - For the 2006 Endocrine' News, we discuss the SERMs and their clinical effects. After the disappointing results of the recent studies on the cardiovascular effects of post-menopausal estrogen replacement therapy, the SERMs show no favourable effects on cardiovascular events either and even a small increase in stroke incidence. The second topic is focused on the controversial diagnosis and treatment of andropause. Finally, in the field of endocrine reproduction, there is some doubt about the optimal time at which a couple actively trying to have a child needs to undertake in vitro fertilization. A recent study suggests that patience may be rewarding. PMID- 17354655 TI - [What's new in gynecology in 2006?]. AB - There were two good news in gynecologic oncology in 2006: intraperitoneal (IP) chemotherapy and the prophylactic vaccines for human papilloma virus (HPV). The ovarian cancer is usually limited to the peritoneal cavity and IP chemotherapy is associated with increased local concentrations. A benefit of this approach on survival was shown in three randomized trials and justifies the recommendation of this treatment for women with a Stage III ovarian cancer, after optimal surgery. Randomized trials have demonstrated the efficacy of two HPV vaccines to prevent a new infection and cytological abnormalities of the cervix. These vaccines will soon be available in Switzerland. PMID- 17354656 TI - [Arterial hypertension. Factors favoring long-term compliance with therapy]. AB - Achieving blood pressure control in every hypertensive patients remains a difficult task despite the availability of a several types of agents lowering blood pressure by different mechanisms. The choice of initial therapy is important. Starting therapy using a blocker of the renin-angiotensin system increases the probability that the patients remain on the same drug during long term treatment. Fixed-dose combinations, by improving blood pressure control without impairing tolerability, also facilitate persistence with therapy. Furthermore, stability of treatment has a positive impact on drug-associated costs. PMID- 17354657 TI - [Infectious diseases (beside AIDS)]. AB - Important epidemiological developments include the continuing dissemination of Influenza A H5N1. It is not adapted to human beings, but its potential to cause a pandemic is confirmed. Chikungunya has spread around the Indian Ocean. A new resistant Staphylococcus aureus in increasingly prevalent in the community. Finally, a virulent strain of Clostridium difficile is emerging in North America and Europe. New therapeutic developments are scarce. Several studies promote a rational use of available antibiotics, for instance through wait-and-see prescription for acute otitis media, or appropriate use of urinary cultures in elderly patients. A new Papillomavirus vaccine is now available for prevention of cervical cancer. PMID- 17354658 TI - [Adolescent medicine male clinic]. AB - The vast majority of Swiss adolescents see a physician at least once a year. However, a sizeable proportion of them indicate that they don't have the opportunity to address their own concerns and problems. While female adolescents have access to health care in the field of sexual and reproductive health through family planning clinics, this is not the case of adolescent males. The "clinic for boys only" is an open space for adolescent males where they can bring questions and health problems related to their body, their growth and their puberty, just as their difficulties and their fears regarding their normality, their sexuality, their feelings, sexual dysfunctions and questions related to violence within the couple. They can also get information/treatment in the area of sexually transmitted infections. PMID- 17354659 TI - [Nephrology]. AB - ABO incompatibility and positive cross match between the donor and the recipient are no longer considered absolute counter indications to renal transplantation. One-year and 5-years graft survival are similar to ABO compatible transplantation, although a higher incidence of acute humoral rejection is observed. Calcineurin inhibitors nephrotoxicity can be reduced since the introduction of new immunosuppressive drugs. Two forms of peritoneal dialysis are available: continuous ambulatory peritoneal dialysis and automated peritoneal dialysis. In each situation the treatment must be tailored to the patient. Various clinical and biological parameters allow to judge the adequacy of the peritoneal dialysis. The last guidelines fixed the minimal target value of one of them, the Kt/V, at 1.7. PMID- 17354660 TI - [Neurology]. AB - Neurology is a polymorphic discipline, with several subspecialties. In 2006, as in the previous years, a huge amount of scientific work focusing on treatment has been published. However, there has not been a true revolution in any of the current therapeutic strategies; rather, we experienced an improvement in the knowledge about several specific "details". This allows to consider more and more variables when administering a specific treatment, therefore, in each subspecialty a move towards a better patient's care has been made. In this contribution, several specialists analyse and interpret new facts about their respective neurological domain. PMID- 17354661 TI - [Medical oncology]. AB - The 2006 vintage leads to decreased enthusiasm in medical oncology, compared to the amazing 2005. One notable exception is the marketing of sunitinib and sorafenib, two agents which increase remarkably the chances of benefiting renal cell cancer patients. Several of the reviewed papers indicate the need to better target cancer treatment, including chemotherapy. One may hope that the near future will deliver on this, leading to an increased treatment effectiveness and decreased exposure to unjustified toxicity. PMID- 17354662 TI - [Pneumology. Anti-IgE antibodies in the treatment of asthma]. AB - Omalizumab is a humanized monoclonal antibody that is directed against IgE. It has been shown to improve the control of severe allergic asthma in adults and adolescents. Candidates to the treatment are asthmatic patients with positive prick tests and/or in vitro markers of allergy, altered pulmonary function tests, and persistent daytime or nocturnal symptoms despite appropriate treatment with inhaled corticosteroids and long-acting beta-2-agonists. PMID- 17354663 TI - [Rhumatology. The rheumatoid arthritis patient who does not respond to anti-TNF]. AB - Anti-TNF treatments have given patients with rheumatoid arthritis considerable hope and relief. However, 20-30% of patients do not respond sufficiently to a given anti-TNF drug. In this situation, current strategies include switching to an alternative agent, increasing the dose of the current agent or to return to conventional DMARDs. The arrival of new biologics, which target different molecules than TNF, opens the perspective to other pathways of immunomodulation in RA. These drugs include rituximab (anti-CD20), abatacept (CTLA4Ig) and tocilizumab (anti- IL6R). Comparative studies are urgently needed to assess the efficacy of the different treatment options in order to provide the best therapeutic strategy for our patients. PMID- 17354664 TI - [First glance at the 2007 national immunization plan]. AB - The essential modifications of practices to be applied in 2007 concern the immunization of young children and adolescents against pneumococcus and group C meningococcus, the vaccine catch-up of young adults (including future mothers) and the protection of those likely to be exposed to tick-borne encephalitis. New fact-sheets on immunizations, duly validated, have been introduced to guarantee patients' right to information and support physicians in their daily activities. Recommendations about new vaccines, such as against cervical cancer, will be communicated in real time to all the physicians registered at InfoVac. PMID- 17354665 TI - [Treatment of HIV infection in 2006: highlights]. AB - In developed countries, drug therapy has turned HIV infection into a chronic disease. More is known about viral replication and new, easily tolerated drugs will enter the marketplace in 2007 and 2008. For the majority of patients who suffer neither resistance nor intolerance, older molecules are combined in the same pill. Very effective triple therapy, combining efavirenz, emtricitabine, and tenofovir in one pill (Atripla - Gilead) is already available in the United States and will become the standard of therapy in 2007. Since the eradication of the virus remains impossible even under effective antiretroviral therapy, the scheduled treatment interruptions as well as simplified maintenance therapies represent still a topic of interest for well selected patients, with an aim of reducing the costs and toxicities. PMID- 17354666 TI - [Mrs. C.'s chronic abdominal pain]. PMID- 17354667 TI - [Thoughts about a large glass]. PMID- 17354668 TI - [Human bodies at the auction block]. PMID- 17354669 TI - [Bronchiolitis: the antibiotic treatment might become automatic]. PMID- 17354670 TI - [When the mother guides the brain development of her future child]. PMID- 17354671 TI - [Small questions facing the future]. PMID- 17354672 TI - From alveolar diffuse atrophy to aggressive periodontitis: a brief history. AB - Technologic advances in mechanics, electronics, physics, chemistry, and computer science have contributed to advances in dental medicine. Periodontology is not only a clinical science but is also directly related to the basic sciences. Research is conducted in laboratories rather than in clinics now. During the last century, aggressive periodontitis has received attention from numerous researchers because of its multifactorial features. This paper explores the long scientific journey of aggressive periodontitis, beginning with its first definition as alveolar diffuse atrophy. Perhaps in the future, "alveolar diffuse atrophy" will be referred to by another name or term. However, this journey will never end. PMID- 17354673 TI - Dental postcards no. XXXV. Dental postcard caption: "Good for the old man that ma has the toothache". PMID- 17354674 TI - The humanitarian service of dentists in Grenfell's sub-Arctic Labrador: 1910 1930. AB - Little has been written about peacetime humanitarian work in dentistry. In particular, few know the achievement of dentists who served with Dr. Wilfred Grenfell's medical mission in the early 1900s. These volunteers introduced dentistry to the impoverished coasts of Labrador and North Newfoundland, working under primitive conditions to meet an incredible need for dental care. This work constitutes an important chapter in the history of humanitarian dental service. As Dr. Grenfell himself noted, "the gospel of prosthetic and prophylactic dentistry in a distant, foreign country on a scale of this kind is entirely unique in the world's field of dentistry, so far as I can find". PMID- 17354675 TI - Dentistry on stamps. PMID- 17354676 TI - "All I want for Christmas is my two front teeth" (the story behind the song). AB - During his long and productive career, Donald Yetter Gardner (1913-2004) played various musical instruments, directed church choirs, wrote contemporary church anthems and led many community-sponsored choral events. Additionally, he penned a number of popular spirituals, including "Man Shall Not Live By Bread Alone," and "O Give Thanks Unto the Lord". He was noted for his varied musical accomplishments, but he was best known for composing what was to become an international childrens holiday favorite, "All I Want For Christmas Is My Two Front Teeth". PMID- 17354677 TI - Dental trade cards XXII. 19th century dentistry advertising trade cards. PMID- 17354678 TI - Dr. Robert Semple--the dentist behind the annexation of California. 2006 Orland Memorial Lecture. PMID- 17354679 TI - Dental postcards no. XXXVI. Here's something to look into! Latest American dentistry. PMID- 17354680 TI - A unified information-theoretic approach to groupwise non-rigid registration and model building. AB - The non-rigid registration of a group of images shares a common feature with building a model of a group of images: a dense, consistent correspondence across the group. Image registration aims to find the correspondence, while modelling requires it. This paper presents the theoretical framework required to unify these two areas, providing a groupwise registration algorithm, where the inherently groupwise model of the image data becomes an integral part of the registration process. The performance of this algorithm is evaluated by extending the concepts of generalisability and specificity from shape models to image models. This provides an independent metric for comparing registration algorithms of groups of images. Experimental results on MR data of brains for various pairwise and groupwise registration algorithms is presented, and demonstrates the feasibility of the combined registration/modelling framework, as well as providing quantitative evidence for the superiority of groupwise approaches to registration. PMID- 17354681 TI - Hypothesis testing with nonlinear shape models. AB - We present a method for two-sample hypothesis testing for statistical shape analysis using nonlinear shape models. Our approach uses a true multivariate permutation test that is invariant to the scale of different model parameters and that explicitly accounts for the dependencies between variables. We apply our method to m-rep models of the lateral ventricles to examine the amount of shape variability in twins with different degrees of genetic similarity. PMID- 17354682 TI - Extrapolation of sparse tensor fields: application to the modeling of brain variability. AB - Modeling the variability of brain structures is a fundamental problem in the neurosciences. In this paper, we start from a dataset of precisely delineated anatomical structures in the cerebral cortex: a set of 72 sulcal lines in each of 98 healthy human subjects. We propose an original method to compute the average sulcal curves, which constitute the mean anatomy in this context. The second order moment of the sulcal distribution is modeled as a sparse field of covariance tensors (symmetric, positive definite matrices). To extrapolate this information to the full brain, one has to overcome the limitations of the standard Euclidean matrix calculus. We propose an affine-invariant Riemannian framework to perform computations with tensors. In particular, we generalize radial basis function (RBF) interpolation and harmonic diffusion PDEs to tensor fields. As a result, we obtain a dense 3D variability map which proves to be in accordance with previously published results on smaller samples subjects. Moreover, leave one (sulcus) out tests show that our model is globally able to recover the missing information when there is a consistent neighboring variability. Last but not least, we propose innovative methods to analyze the asymmetry of brain variability. As expected, the greatest asymmetries are found in regions that includes the primary language areas. Interestingly, such an asymmetry in anatomical variance could explain why there may be greater power to detect group activation in one hemisphere than the other in fMRI studies. PMID- 17354683 TI - Bayesian population modeling of effective connectivity. AB - A hierarchical model based on the Multivariate Autoregessive (MAR) process is proposed to jointly model neurological time-series collected from multiple subjects, and to characterize the distribution of MAR coefficients across the population from which those subjects were drawn. Thus, inference about effective connectivity between brain regions may be generalized beyond those subjects studied. The posterior on population- and subject-level connectivity parameters are estimated in a Variational Bayesian (VB) framework, and structural model parameters are chosen by the corresponding evidence criteria. The significance of resulting connectivity statistics are evaluated by permutation-based approximations to the null distribution. The method is demonstrated on simulated data and on actual multi-subject neurological time-series. PMID- 17354684 TI - Fiber tracking in q-ball fields using regularized particle trajectories. AB - Most of the approaches dedicated to fiber tracking from diffusion-weighted MR data rely on a tensor model. However, the tensor model can only resolve a single fiber orientation within each imaging voxel. New emerging approaches have been proposed to obtain a better representation of the diffusion process occurring in fiber crossing. In this paper, we adapt a tracking algorithm to the q-ball representation, which results from a spherical Radon transform of high angular resolution data. This algorithm is based on a Monte-Carlo strategy, using regularized particle trajectories to sample the white matter geometry. The method is validated using a phantom of bundle crossing made up of haemodialysis fibers. The method is also applied to the detection of the auditory tract in three human subjects. PMID- 17354685 TI - Approximating anatomical brain connectivity with diffusion tensor MRI using kernel-based diffusion simulations. AB - We present a new technique for noninvasively tracing brain white matter fiber tracts using diffusion tensor magnetic resonance imaging (DT-MRI). This technique is based on performing diffusion simulations over a series of overlapping three dimensional diffusion kernels that cover only a small portion of the human brain volume and are geometrically centered upon selected starting voxels where a seed is placed. Synthetic and real DT-MRI data are employed to demonstrate the tracking scheme. It is shown that the synthetic tracts can be accurately replicated, while several major white matter fiber pathways in the human brain can be reproduced noninvasively as well. The primary advantages of the algorithm lie in the handling of fiber branching and crossing and its seamless adaptation to the platform established by new imaging techniques, such as high angular, q space, or generalized diffusion tensor imaging. PMID- 17354686 TI - Maximum entropy spherical deconvolution for diffusion MRI. AB - This paper proposes a maximum entropy method for spherical deconvolution. Spherical deconvolution arises in various inverse problems. This paper uses the method to reconstruct the distribution of microstructural fibre orientations from diffusion MRI measurements. Analysis shows that the PASMRI algorithm, one of the most accurate diffusion MRI reconstruction algorithms in the literature, is a special case of the maximum entropy spherical deconvolution. Experiments compare the new method to linear spherical deconvolution, used previously in diffusion MRI, and to the PASMRI algorithm. The new method compares favourably both in simulation and on standard brain-scan data. PMID- 17354687 TI - From spatial regularization to anatomical priors in fMRI analysis. AB - In this paper, we study Markov Random Fields as spatial smoothing priors in fMRI detection. Relatively high noise in fMRI images presents a serious challenge for the detection algorithms, creating a need for spatial regularization of the signal. Gaussian smoothing, traditionally employed to boost the signal-to-noise ratio, often removes small activation regions. Recently, the use of Markov priors has been suggested as an alternative regularization approach. In this work, we investigate fast approximate inference algorithms for using MRFs in fMRI detection, propose a novel way to incorporate anatomical information into the detection framework, validate the methods through ROC analysis on simulated data and demonstrate their application in a real fMRI study. PMID- 17354688 TI - CLASSIC: consistent longitudinal alignment and segmentation for serial image computing. AB - This paper proposes a temporally-consistent and spatially-adaptive longitudinal MR brain image segmentation algorithm, referred to as CLASSIC, which aims at obtaining accurate measurements of rates of change of regional and global brain volumes from serial MR images. The algorithm incorporates image-adaptive clustering, spatiotemporal smoothness constraints, and image warping to jointly segment a series of 3-D MR brain images of the same subject that might be undergoing changes due to development, aging or disease. Morphological changes, such as growth or atrophy, are also estimated as part of the algorithm. Experimental results on simulated and real longitudinal MR brain images show both segmentation accuracy and longitudinal consistency. PMID- 17354689 TI - Robust active appearance model matching. AB - A novel robust active appearance model (AAM) matching algorithm is presented. The method consists of two main stages. First, initial residuals are clustered by a non parametric mean shift mode detection step. Second, modes without gross outliers are selected using an objective function. Robustness of the matching procedure is demonstrated on a variety of examples with different noise conditions. The proposed algorithm outperformed the conventional AAM matching on images with gross disturbances and can tolerate up to 40% of disturbed data. PMID- 17354690 TI - Simultaneous segmentation and registration of contrast-enhanced breast MRI. AB - Breast Contrast-Enhanced MRI (ce-MRI) requires a series of images to be acquired before, and repeatedly after, intravenous injection of a contrast agent. Breast MRI segmentation based on the differential enhancement of image intensities can assist the clinician detect suspicious regions. Image registration between the temporal data sets is necessary to compensate for patient motion, which is quite often substantial. Although segmentation and registration are usually treated as separate problems in medical image analysis, they can naturally benefit a great deal from each other. In this paper, we propose a scheme for simultaneous segmentation and registration of breast ce-MRI. It is developed within a Bayesian framework, based on a maximum a posteriori estimation method. A pharmacokinetic model and Markov Random Field model have been incorporated into the framework in order to improve the performance of our algorithm. Our method has been applied to the segmentation and registration of clinical ce-MR images. The results show the potential of our methodology to extract useful information for breast cancer detection. PMID- 17354691 TI - Multiscale vessel enhancing diffusion in CT angiography noise filtering. AB - Filtering of vessel structures in medical images by analyzing the second order information or the Hessian of the image, is a well known technique. In this work we incorporate Frangi's multiscale vessel filter, which is based on a geometrical analysis of the Hessian' eigenvectors, into a nonlinear, anisotropic diffusion scheme, such that diffusion mainly takes place along the vessel axis while diffusion perpendicular to this axis is inhibited. The multiscale character of the vesselness filter ensures an equally good response for varying vessel radii. The first, theoretical contribution of this paper is the modification of the original formulation of this vessel filter, such that it becomes a smooth function on its domain which is a necessary condition imposed by the diffusion process to ensure well-posedness. The second contribution concerns the application of noise filtering of 3D synthetic, phantom computed tomography (CT) and patient CT data. It is shown that the method is very effective in noise filtering, illustrating its potential as a preprocessing step in the analysis of low dose CT angiography. PMID- 17354692 TI - Information fusion in biomedical image analysis: combination of data vs. combination of interpretations. AB - Information fusion has, in the form of multiple classifier systems, long been a successful tool in pattern recognition applications. It is also becoming increasingly popular in biomedical image analysis, for example in computer-aided diagnosis and in image segmentation. In this paper, we extend the principles of multiple classifier systems by considering information fusion of classifier inputs rather than on their outputs, as is usually done. We introduce the distinction between combination of data (i.e., classifier inputs) vs. combination of interpretations (i.e., classifier outputs). We illustrate the two levels of information fusion using four different biomedical image analysis applications that can be implemented using fusion of either data or interpretations: atlas based image segmentation, "average image" tissue classification, multi-spectral classification, and deformation-based group morphometry. PMID- 17354693 TI - Parametric medial shape representation in 3-D via the Poisson partial differential equation with non-linear boundary conditions. AB - This paper presents a new shape representation for a special class of 3-D objects. In a generative approach to object modeling inspired by m-reps, skeletons of objects are explicitly defined as continuous manifolds and boundaries are derived from the skeleton by a process that involves solving a Poisson PDE with a non-linear boundary condition. This formulation helps satisfy the equality constraints that are imposed on the parameters of the representation by rules of medial geometry. One benefit of the new approach is the ability to represent different instances of an anatomical structure using a common parametrization domain, simplifying the problem of computing correspondences between instances. Another benefit is the ability to continuously parameterize the volumetric region enclosed by the representation's boundary in a one-to-one and onto manner, in a way that preserves two of the three coordinates of the parametrization along vectors normal to the boundary. These two features make the new representation an attractive candidate for statistical analysis of shape and appearance. In this paper, the representation is carefully defined and the results of fitting the hippocampus in a deformable templates framework are presented. PMID- 17354694 TI - Diffeomorphic nonlinear transformations: a local parametric approach for image registration. AB - Many types of transformations are used to model deformations in medical image registration. While some focus on modeling local changes, some on continuity and invertibility, there is no closed-form nonlinear parametric approach that addresses all these properties. This paper presents a class of nonlinear transformations that are local, continuous and invertible under certain conditions. They are straightforward to implement, fast to compute and can be used particularly in cases where locally affine deformations need to be recovered. We use our new transformation model to demonstrate some results on synthetic images using a multi-scale approach to multi-modality mutual information based image registration. The original images were deformed using B splines at three levels of scale. The results show that the proposed method can recover these deformations almost completely with very few iterations of a gradient based optimizer. PMID- 17354695 TI - A framework for registration, statistical characterization and classification of cortically constrained functional imaging data. AB - We present a framework for registering and analyzing functional neuroimaging data constrained to the cortical surface of the brain. We assume as input a set of labeled data points that lie on a set of parameterized topologically spherical surfaces that represent the cortical surfaces of multiple subjects. To perform analysis across subjects, we first co-register the coordinates from each surface to a cortical atlas using labeled sulcal maps as constraints. The registration minimizes a thin plate spline energy function on the deforming surface using covariant derivatives to solve the associated PDEs in the intrinsic geometry of the individual surface. The resulting warps are used to bring the functional data for multiple subjects into a common surface atlas coordinate system. We then present a novel method for performing statistical analysis of points on this atlas surface. We use the Green's function of the heat equation on the surface to model probability distributions and thus demonstrate the use of PDEs for statistical analysis in Riemannian manifolds. We describe methods for estimating the mean and variance of a set of points, such that the mean also lies in the manifold. We demonstrate the utility of this framework in the development of a maximum likelihood classifier for parcellation of somatosensory cortex in the atlas based on current dipole fits to MEG data, simulated to represent a somatotopic mapping of S1 sensory areas in multiple subjects. PMID- 17354696 TI - PET image reconstruction: a robust state space approach. AB - Statistical iterative reconstruction algorithms have shown improved image quality over conventional nonstatistical methods in PET by using accurate system response models and measurement noise models. Strictly speaking, however, PET measurements, pre-corrected for accidental coincidences, are neither Poisson nor Gaussian distributed and thus do not meet basic assumptions of these algorithms. In addition, the difficulty in determining the proper system response model also greatly affects the quality of the reconstructed images. In this paper, we explore the usage of state space principles for the estimation of activity map in tomographic PET imaging. The proposed strategy formulates the organ activity distribution through tracer kinetics models, and the photon-counting measurements through observation equations, thus makes it possible to unify the dynamic reconstruction problem and static reconstruction problem into a general framework. Further, it coherently treats the uncertainties of the statistical model of the imaging system and the noisy nature of measurement data. Since H(infinity) filter seeks minimummaximum-error estimates without any assumptions on the system and data noise statistics, it is particular suited for PET image reconstruction where the statistical properties of measurement data and the system model are very complicated. The performance of the proposed framework is evaluated using Shepp-Logan simulated phantom data and real phantom data with favorable results. PMID- 17354697 TI - Multi-dimensional mutual information based robust image registration using maximum distance-gradient-magnitude. AB - In this paper, a novel spatial feature, namely maximum distance-gradient magnitude (MDGM), is defined for registration tasks. For each voxel in an image, the MDGM feature encodes spatial information at a global level, including both edges and distances. We integrate the MDGM feature with intensity into a two element attribute vector and adopt multi-dimensional mutual information as a similarity measure on the vector space. A multi-resolution registration method is then proposed for aligning multi-modal images. Experimental results show that, as compared with the conventional mutual information (MI)-based method, the proposed method has longer capture ranges at different image resolutions. This leads to more robust registrations. Around 1200 randomized registration experiments on clinical 3D MR-T1, MR-T2 and CT datasets demonstrate that the new method consistently gives higher success rates than the traditional MI-based method. Moreover, it is shown that the registration accuracy of our method obtains sub voxel level and is acceptably high. PMID- 17354699 TI - Topology preserving tissue classification with fast marching and topology templates. AB - This paper presents a novel approach for object segmentation in medical images that respects the topological relationships of multiple structures as given by a template. The algorithm combines advantages of tissue classification, digital topology, and level-set evolution into a topology-invariant multiple-object fast marching method. The technique can handle any given topology and enforces object level relationships with little constraint over the geometry. Applied to brain segmentation, it sucessfully extracts gray matter and white matter structures with the correct spherical topology without topology correction or editing of the subcortical structures. PMID- 17354698 TI - Tissue perfusion diagnostic classification using a spatio-temporal analysis of contrast ultrasound image sequences. AB - The analysis of tissue perfusion in myocardial contrast echocardiography (MCE) remains a qualitative process dependent on visual inspection by a clinician. Fully automatic techniques that can quantify tissue perfusion accurately has yet to be developed. In this paper, a novel spatio-temporal technique is described for segmenting the myocardium into differently perfused regions and obtaining quantitative perfusion indices, representing myocardial blood flow and blood flow reserve. Using these indices, Myocardial segments in 22 patients were classed as either healthy or diseased, and results compared to coronary angiogram analysis and an experienced clinician. The results show that the automatic method works as well as a human at detecting areas of ischaemia, but in addition localizes the spatial extent of each perfused region as well. To our knowledge this is the first reported spatio-temporal method developed and evaluated for MCE assessment. PMID- 17354700 TI - Apparent diffusion coefficient approximation and diffusion anisotropy characterization in DWI. AB - We present a new approximation for the apparent diffusion coefficient (ADC) of non-Gaussian water diffusion with at most two fiber orientations within a voxel. The proposed model approximates ADC profiles by product of two spherical harmonic series (SHS) up to order 2 from High Angular Resolution Diffusion-weighted (HARD) MRI data. The coefficients of SHS are estimated and regularized simultaneously by solving a constrained minimization problem. An equivalent but non-constrained version of the approach is also provided to reduce the complexity and increase the efficiency in computation. Moreover we use the Cumulative Residual Entropy (CRE) as a measurement to characterize diffusion anisotropy. By using CRE we can get reasonable results with two thresholds, while the existing methods either can only be used to characterize Gaussian diffusion or need more measurements and thresholds to classify anisotropic diffusion with two fiber orientations. The experiments on HARD MRI human brain data indicate the effectiveness of the method in the recovery of ADC profiles. The characterization of diffusion based on the proposed method shows a consistency between our results and known neuroanatomy. PMID- 17354701 TI - Linearization of mammograms using parameters derived from noise characteristics. AB - A method is proposed for converting digitized mammograms to a normalized representation, in which pixel values are linearly related to the logarithm of x ray exposure. This method is based on a signal dependent noise model. By exploiting this model unknown parameters of the non-linear response of the film screen system can be estimated from signal dependence of the image noise. The method was applied to a series of 1372 mammograms acquired over a period of 8 years. Sudden changes in estimated parameters corresponded well with the introduction of new film-screen systems. PMID- 17354702 TI - Knowledge-driven automated detection of pleural plaques and thickening in high resolution CT of the lung. AB - Consistent efforts are being made to build Computer-Aided Detection and Diagnosis systems for radiological images. Such systems depend on automated detection of various disease patterns, which are then combined together to obtain differential diagnosis. For diffuse lung diseases, over 12 disease patterns are of interest in High Resolution Computed Tomography (HRCT) scans of the lung. In this paper, we present an automated detection method for two such patterns, namely Pleural Plaque and Diffuse Pleural Thickening. These are characteristic features of asbestos-related benign pleural disease. The attributes used for detection are derived from anatomical knowledge and the heuristics normally used by radiologists, and are computed automatically for each scan. A probabilistic model built on the attributes using naive Bayes classifier is applied to recognise the features in new scans, and preliminary results are presented. The technique is tested on 140 images from 13 studies and validated by an experienced radiologist. PMID- 17354703 TI - Fundamental limits in 3D landmark localization. AB - This work analyses the accuracy of estimating the location of 3D landmarks and characteristic image structures. Based on nonlinear estimation theory we study the minimal stochastic errors of the position estimate caused by noisy data. Given analytic models of the image intensities we derive closed-form expressions for the Cramer-Rao bound for different 3D structures such as 3D edges, 3D ridges, 3D lines, and 3D blobs. It turns out, that the precision of localization depends on the noise level, the size of the region-of-interest, the width of the intensity transitions, as well as on other parameters describing the considered image structure. The derived lower bounds can serve as benchmarks and the performance of existing algorithms can be compared with them. To give an impression of the achievable accuracy numeric examples are presented. Moreover, by experimental investigations we demonstrate that the derived lower bounds can be achieved by fitting parametric intensity models directly to the image data. PMID- 17354704 TI - Computational elastography from standard ultrasound image sequences by global trust region optimization. AB - A new approach is proposed to estimate the spatial distribution of shear modulus of tissues in-vivo. An image sequence is acquired using a standard medical ultrasound scanner while varying the force applied to the handle. The elastic properties are then recovered simultaneously with the inter-frame displacement fields using a computational procedure based on finite element modeling and trust region constrained optimization. No assumption about boundary conditions is needed. The optimization procedure is global, taking advantage of all available images. The algorithm was tested on phantom, as well as on real clinical images. PMID- 17354705 TI - Representing diffusion MRI in 5D for segmentation of white matter tracts with a level set method. AB - We present a method for segmenting white matter tracts from high angular resolution diffusion MR. images by representing the data in a 5 dimensional space of position and orientation. Whereas crossing fiber tracts cannot be separated in 3D position space, they clearly disentangle in 5D position-orientation space. The segmentation is done using a 5D level set method applied to hyper-surfaces evolving in 5D position-orientation space. In this paper we present a methodology for constructing the position-orientation space. We then show how to implement the standard level set method in such a non-Euclidean high dimensional space. The level set theory is basically defined for N-dimensions but there are several practical implementation details to consider, such as mean curvature. Finally, we will show results from a synthetic model and a few preliminary results on real data of a human brain acquired by high angular resolution diffusion MRI. PMID- 17354706 TI - Automatic prediction of myocardial contractility improvement in stress MRI using shape morphometrics with independent component analysis. AB - An important assessment in patients with ischemic heart disease is whether myocardial contractility may improve after treatment. The prediction of myocardial contractility improvement is generally performed under physical or pharmalogical stress conditions. In this paper, we present a technique to build a statistical model of healthy myocardial contraction using independent component analysis. The model is used to detect regions with abnormal contraction in patients both during rest and stress. PMID- 17354707 TI - Brain segmentation with competitive level sets and fuzzy control. AB - We propose to segment 3D structures with competitive level sets driven by fuzzy control. To this end, several contours evolve simultaneously toward previously defined anatomical targets. A fuzzy decision system combines the a priori knowledge provided by an anatomical atlas with the intensity distribution of the image and the relative position of the contours. This combination automatically determines the directional term of the evolution equation of each level set. This leads to a local expansion or contraction of the contours, in order to match the borders of their respective targets. Two applications are presented: the segmentation of the brain hemispheres and the cerebellum, and the segmentation of deep internal structures. Experimental results on real MR images are presented, quantitatively assessed and discussed. PMID- 17354708 TI - Coupled shape distribution-based segmentation of multiple objects. AB - In this paper we develop a multi-object prior shape model for use in curve evolution-based image segmentation. Our prior shape model is constructed from a family of shape distributions (cumulative distribution functions) of features related to the shape. Shape distribution-based object representations possess several desired properties, such as robustness, invariance, and good discriminative and generalizing properties. Further, our prior can capture information about the interaction between multiple objects. We incorporate this prior in a curve evolution formulation for shape estimation. We apply this methodology to problems in medical image segmentation. PMID- 17354709 TI - Partition-based extraction of cerebral arteries from CT angiography with emphasis on adaptive tracking. AB - In this paper a method to extract cerebral arteries from computed tomographic angiography (CTA) is proposed. Since CTA shows both bone and vessels, the examination of vessels is a difficult task. In the upper part of the brain, the arteries of main interest are not close to bone and can be well segmented out by thresholding and simple connected-component analysis. However in the lower part the separation is challenging due to the spatial closeness of bone and vessels and their overlapping intensity distributions. In this paper a CTA volume is partitioned into two sub-volumes according to the spatial relationship between bone and vessels. In the lower sub-volume, the concerning arteries are extracted by tracking the center line and detecting the border on each cross-section. The proposed tracking method can be characterized by the adaptive properties to the case of cerebral arteries in CTA. These properties improve the tracking continuity with less user-interaction. PMID- 17354710 TI - Regional whole body fat quantification in mice. AB - Obesity has risen to epidemic levels in the United States and around the world. Global indices of obesity such as the body mass index (BMI) have been known to be inaccurate predictors of risk of diabetes, and it is commonly recognized that the distribution of fat in the body is a key measure. In this work, we describe the early development of image analysis methods to quantify regional body fat distribution in groups of both male and female wildtype mice using magnetic resonance images. In particular, we present a new formulation which extends the expectation-maximization formalism commonly applied in brain segmentation to multi-exponential data and applies it to the problem of regional whole body fat quantification. Previous segmentation approaches for multispectral data typically perform the classification on fitted parameters, such as the density and the relaxation times. In contrast, our method directly computes a likelihood term from the raw data and hence explicitly accounts for errors in the fitting process, while still using the fitted parameters to model the variation in the appearance of each tissue class. Early validation results, using magnetic resonance spectroscopic imaging as a gold standard, are encouraging. We also present results demonstrating differences in fat distribution between male and female mice. PMID- 17354711 TI - Surface matching via currents. AB - We present a new method for computing an optimal deformation between two arbitrary surfaces embedded in Euclidean 3-dimensional space. Our main contribution is in building a norm on the space of surfaces via representation by currents of geometric measure theory. Currents are an appropriate choice for representations because they inherit natural transformation properties from differential forms. We impose a Hilbert space structure on currents, whose norm gives a convenient and practical way to define a matching functional. Using this Hilbert space norm, we also derive and implement a surface matching algorithm under the large deformation framework, guaranteeing that the optimal solution is a one-to-one regular map of the entire ambient space. We detail an implementation of this algorithm for triangular meshes and present results on 3D face and medical image data. PMID- 17354712 TI - A genetic algorithm for the topology correction of cortical surfaces. AB - We propose a technique to accurately correct the spherical topology of cortical surfaces. We construct a mapping from the original surface onto the sphere to detect topological defects as minimal non-homeomorphic regions. A genetic algorithm corrects each defect by finding the maximum-a-posteriori retessellation in a Bayesian framework. During the genetic search, incorrect vertices are iteratively identified and eliminated, while the optimal retessellation is constructed. Applied to synthetic and real data, our method generates optimal topological corrections with only a few iterations. PMID- 17354713 TI - Simultaneous segmentation of multiple closed surfaces using optimal graph searching. AB - This paper presents a general graph-theoretic technique for simultaneously segmenting multiple closed surfaces in volumetric images, which employs a novel graph-construction scheme based on triangulated surface meshes obtained from a topological presegmentation. The method utilizes an efficient graph-cut algorithm that guarantees global optimality of the solution under given cost functions and geometric constraints. The method's applicability to difficult biomedical image analysis problems was demonstrated in a case study of co-segmenting the bone and cartilage surfaces in 3-D magnetic resonance (MR) images of human ankles. The results of our automated segmentation were validated against manual tracings in 55 randomly selected image slices. Highly accurate segmentation results were obtained, with signed surface positioning errors for the bone and cartilage surfaces being 0.02 +/- 0.11mm and 0.17 +/- 0.12mm, respectively. PMID- 17354714 TI - A generalized level set formulation of the Mumford-Shah functional for brain MR image segmentation. AB - Brain MR image segmentation is an important research topic in medical image analysis area. In this paper, we propose an active contour model for brain MR image segmentation, based on a generalized level set formulation of the Mumford Shah functional. The model embeds explicitly gradient information into the Mumford-Shah functional, and incorporates in a generic framework both regional and gradient information into segmentation process simultaneously. The proposed method has been evaluated on real brain MR images and the obtained results have shown the desirable segmentation performance. PMID- 17354715 TI - Integrable pressure gradients via harmonics-based orthogonal projection. AB - In the past, several methods based on iterative solution of pressure-Poisson equation have been developed for measurement of pressure from phase-contrast magnetic resonance (PC-MR) data. In this paper, a non-iterative harmonics-based orthogonal projection method is discussed which can keep the pressures measured based on the Navier-Stokes equation independent of the path of integration. The gradient of pressure calculated with Navier-Stokes equation is expanded with a series of orthogonal basis functions, and is subsequently projected onto an integrable subspace. Before the projection step however, a scheme is devised to eliminate the discontinuity at the vessel boundaries. The approach was applied to velocities obtained from computational fluid dynamics (CFD) simulations of stenotic flow and compared with pressures independently obtained by CFD. Additionally, MR velocity data measured in in-vitro phantom models with different degree of stenoses and different flow rates were used to test the algorithm and results were compared with CFD simulations. The pressure results obtained from the new method were also compared with pressures calculated by an iterative solution to the pressure-Poisson equation. Experiments have shown that the proposed approach is faster and is less sensitive to noise. PMID- 17354716 TI - Design of robust vascular tree matching: validation on liver. AB - In this paper, we propose an original and efficient tree matching algorithm for intra-patient hepatic vascular system registration. Vascular systems are segmented from CT-scan images acquired at different times, and then modeled as trees. The goal of this algorithm is to find common bifurcations (nodes) and vessels (edges) in both trees. Starting from the tree root, edges and nodes are iteratively matched. The algorithm works on a set of match solutions that are updated to keep the best matches thanks to a quality criterion. It is robust against topological modifications due to segmentation failures and against strong deformations. Finally, this algorithm is validated on a large synthetic database containing cases with various deformation and segmentation problems. PMID- 17354717 TI - A novel parametric method for non-rigid image registration. AB - This paper presents a novel non-rigid registration method. The main contribution of the method is the modeling of the vorticity (respectively divergence) of the deformation field using vortex (respectively sink and source) particles. Two parameters are associated with a particle: the vorticity (or divergence) strength and the influence domain. This leads to a very compact representation of vorticity and divergence fields. In addition, the optimal position of these particles is determined using a mean shift process. 2D experiments of this method are presented and demonstrate its ability to recover evolving phenomena (MS lesions) so as to register images from 20 patients. PMID- 17354718 TI - Transitive inverse-consistent manifold registration. AB - This paper presents a new registration method called Transitive Inverse Consistent Manifold Registration (TICMR). The TICMR method jointly estimates correspondence maps between groups of three manifolds embedded in a higher dimensional image space while minimizing inverse consistency and transitivity errors. Registering three manifolds at once provides a means for minimizing the transitivity error which is not possible when registering only two manifolds. TICMR is an iterative method that uses the closest point projection operator to define correspondences between manifolds as they are non-rigidly registered. Examples of the TICMR method are presented for matching groups of three contours and groups of three surfaces. The contour registration is regularized by minimizing the change in bending energy of the curves while the surface registration is regularized by minimizing the change in elastic energy of the surfaces. The notions of inverse consistency error (ICE) and transitivity error (TE) are extended from volume registration to manifold registration by using a closest point projection operator. For the experiments in this paper, the TICMR method reduces the average ICE by 200 times (contour)/ 6 times (surface) and the average TE by 40 times (contour)/ 2-4 times (surface) compared to registering with a curvature constraint alone. Furthermore, the TICMR is shown to avoid some local minimum that are not avoided when registering with a curvature constraint alone. PMID- 17354719 TI - Cortical surface alignment using geometry driven multispectral optical flow. AB - Spatial normalization is frequently used to map data to a standard coordinate system by removing inter-subject morphological differences, thereby allowing for group analysis to be carried out. In this paper, we analyze the geometry of the cortical surface using two shape measures that are the key to distinguish sulcal and gyral regions from each other. Then a multispectral optical flow (OF) warping procedure that aims to align the shape measure maps of an atlas and a subject brain's normalized maps is described. The variational problem to estimate the OF field is solved using a Euclidean framework. After warping one brain given the OF result, we obtain a better structural and functional alignment across multiple brains. PMID- 17354720 TI - Inverse consistent mapping in 3D deformable image registration: its construction and statistical properties. AB - This paper presents a new approach to inverse consistent image registration. A uni-directional algorithm is developed using symmetric cost functionals and regularizers. Instead of enforcing inverse consistency using an additional penalty that penalizes inconsistency error, the new algorithm directly models the backward mapping by inverting the forward mapping. The resulting minimization problem can then be solved uni-directionally involving only the forward mapping, without optimizing in the backward direction. Lastly, we evaluated the algorithm by applying it to the serial MRI scans of a clinical case of semantic dementia. The statistical distributions of the local volume change (Jacobian) maps were examined by considering the Kullback-Liebler distances on the material density functions. Contrary to common belief, the values of any non-trivial Jacobian map do not follow a log-normal distribution with zero mean. Statistically significant differences were detected between consistent versus inconsistent matching when permutation tests were performed on the resulting deformation maps. PMID- 17354721 TI - Robust nonrigid multimodal image registration using local frequency maps. AB - Automatic multi-modal image registration is central to numerous tasks in medical imaging today and has a vast range of applications e.g., image guidance, atlas construction, etc. In this paper, we present a novel multi-modal 3D non-rigid registration algorithm where in 3D images to be registered are represented by their corresponding local frequency maps efficiently computed using the Riesz transform as opposed to the popularly used Gabor filters. The non-rigid registration between these local frequency maps is formulated in a statistically robust framework involving the minimization of the integral squared error a.k.a. L2E (L2 error). This error is expressed as the squared difference between the true density of the residual (which is the squared difference between the non rigidly transformed reference and the target local frequency representations) and a Gaussian or mixture of Gaussians density approximation of the same. The non rigid transformation is expressed in a B-spline basis to achieve the desired smoothness in the transformation as well as computational efficiency. The key contributions of this work are (i) the use of Riesz transform to achieve better efficiency in computing the local frequency representation in comparison to Gabor filter-based approaches, (ii) new mathematical model for local-frequency based non-rigid registration, (iii) analytic computation of the gradient of the robust non-rigid registration cost function to achieve efficient and accurate registration. The proposed non-rigid L2E-based registration is a significant extension of research reported in literature to date. We present experimental results for registering several real data sets with synthetic and real non-rigid misalignments. PMID- 17354722 TI - Imaging tumor microenvironment with ultrasound. AB - Recent advances in molecular biology are providing new opportunities for breast cancer imaging. Our approach uses ultrasound to image viscoelastic features of tumors. These features describe microenvironmental factors that stimulate signaling pathways in tumors that ultimately affect metastatic potential and response to traditional therapeutics. This paper explains the motivation for the approach, describes measurements in phantoms and patients, and defines measurement sensitivity using hydrogels with tissue-like features. PMID- 17354723 TI - PDE-based three dimensional path planning for virtual endoscopy. AB - Three dimensional medial paths or curve skeletons (CS) are an essential component of any virtual endoscopy (VE) system, because they serve as flight paths for a virtual camera to navigate the human organ and to examine its internal structures. In this paper, we propose a novel framework for computing flight paths of tubular structures for VE using partial differential equation (PDE). The method works in two passes. In the first pass, the overall topology of the organ is analyzed and its important topological nodes are identified, while in the second pass, the actual flight paths are computed by tracking them starting from each identified node. The proposed framework is robust, fully automatic, computationally efficient, and computes CS that are centered, connected, thin, and less sensitive to boundary noise. We have extensively validated the robustness of the proposed method both quantitatively and qualitatively against several synthetic phantoms and clinical datasets. PMID- 17354724 TI - Elastic shape models for interpolations of curves in image sequences. AB - Many applications in image analysis are concerned with the temporal evolution of shapes in video sequences. In situations involving low-contrast, low-quality images, human aid is often needed to extract shapes from images. An interesting approach is to use expert help to extract shapes in certain well-separated frames, and to use automated methods to extract shapes from intermediate frames. We present a technique to interpolate between expert generated shapes. This technique preserves salient features in the interpolated shapes, and allows analysts to model a continuous evolution of shapes, instead of a coarse sampling generated by the expert. The basic idea is to establish a correspondence between points on the two end shapes, and to construct a geodesic flow on a shape space maintaining that correspondence. This technique is demonstrated using echocardiagraphic images and infrared human gait sequences. PMID- 17354725 TI - Segmenting and tracking the left ventricle by learning the dynamics in cardiac images. AB - Having accurate left ventricle (LV) segmentations across a cardiac cycle provides useful quantitative (e.g. ejection fraction) and qualitative information for diagnosis of certain heart conditions. Existing LV segmentation techniques are founded mostly upon algorithms for segmenting static images. In order to exploit the dynamic structure of the heart in a principled manner, we approach the problem of LV segmentation as a recursive estimation problem. In our framework, LV boundaries constitute the dynamic system state to be estimated, and a sequence of observed cardiac images constitute the data. By formulating the problem as one of state estimation, the segmentation at each particular time is based not only on the data observed at that instant, but also on predictions based on past segmentations. This requires a dynamical system model of the LV, which we propose to learn from training data through an information-theoretic approach. To incorporate the learned dynamic model into our segmentation framework and obtain predictions, we use ideas from particle filtering. Our framework uses a curve evolution method to combine such predictions with the observed images to estimate the LV boundaries at each time. We demonstrate the effectiveness of the proposed approach on a large set of cardiac images. We observe that our approach provides more accurate segmentations than those from static image segmentation techniques, especially when the observed data are of limited quality. PMID- 17354726 TI - 3D active shape models using gradient descent optimization of description length. AB - Active Shape Models are a popular method for segmenting three-dimensional medical images. To obtain the required landmark correspondences, various automatic approaches have been proposed. In this work, we present an improved version of minimizing the description length (MDL) of the model. To initialize the algorithm, we describe a method to distribute landmarks on the training shapes using a conformal parameterization function. Next, we introduce a novel procedure to modify landmark positions locally without disturbing established correspondences. We employ a gradient descent optimization to minimize the MDL cost function, speeding up automatic model building by several orders of magnitude when compared to the original MDL approach. The necessary gradient information is estimated from a singular value decomposition, a more accurate technique to calculate the PCA than the commonly used eigendecomposition of the covariance matrix. Finally, we present results for several synthetic and real world datasets demonstrating that our procedure generates models of significantly better quality in a fraction of the time needed by previous approaches. PMID- 17354727 TI - Capturing anatomical shape variability using B-spline registration. AB - Registration based on B-spline transformations has attracted much attention in medical image processing recently. Non-rigid registration provides the basis for many important techniques, such as statistical shape modeling. Validating the results, however, remains difficult--especially in intersubject registration. This work explores the ability of B-spline registration methods to capture intersubject shape deformations. We study the effect of different established and new shape representations, similarity measures and optimization strategies on the matching quality. To this end we conduct experiments on synthetic shapes representing deformations which typically may arise in intersubject registration, as well as on real patient data of the liver and pelvic bone. The experiments clearly reveal the influence of each component on the registration performance. The results may serve as a guideline for assessing intensity based registration. PMID- 17354728 TI - A Riemannian approach to diffusion tensor images segmentation. AB - We address the problem of the segmentation of cerebral white matter structures from diffusion tensor images. Our approach is grounded on the theoretically well founded differential geometrical properties of the space of multivariate normal distributions. We introduce a variational formulation, in the level set framework, to estimate the optimal segmentation according to the following hypothesis: Diffusion tensors exhibit a Gaussian distribution in the different partitions. Moreover, we must respect the geometric constraints imposed by the interfaces existing among the cerebral structures and detected by the gradient of the diffusion tensor image. We validate our algorithm on synthetic data and report interesting results on real datasets. We focus on two structures of the white matter with different properties and respectively known as the corpus callosum and the corticospinal tract. PMID- 17354729 TI - Coil sensitivity estimation for optimal SNR reconstruction and intensity inhomogeneity correction in phased array MR imaging. AB - Magnetic resonance (MR) images can be acquired by multiple receiver coil systems to improve signal-to-noise ratio (SNR) and to decrease acquisition time. The optimal SNR images can be reconstructed from the coil data when the coil sensitivities are known. In typical MR imaging studies, the information about coil sensitivity profiles is not available. In such cases the sum-of-squares (SoS) reconstruction algorithm is usually applied. The intensity of the SoS reconstructed image is modulated by a spatially variable function due to the non uniformity of coil sensitivities. Additionally, the SoS images also have sub optimal SNR and bias in image intensity. All these effects might introduce errors when quantitative analysis and/or tissue segmentation are performed on the SoS reconstructed images. In this paper, we present an iterative algorithm for coil sensitivity estimation and demonstrate its applicability for optimal SNR reconstruction and intensity inhomogeneity correction in phased array MR imaging. PMID- 17354730 TI - Many heads are better than one: jointly removing bias from multiple MRIs using nonparametric maximum likelihood. AB - The correction of multiplicative bias in magnetic resonance images is an important problem in medical image processing, especially as a preprocessing step for quantitative measurements and other numerical procedures. Most previous approaches have used a maximum likelihood method to increase the probability of the pixels in a single image by adaptively estimating a correction to the unknown image bias field. The pixel probabilities are defined either in terms of a pre existing tissue model, or nonparametrically in terms of the image's own pixel values. In both cases, the specific location of a pixel in the image does not influence the probability calculation. Our approach, similar to methods of joint registration, simultaneously eliminates the bias from a set of images of the same anatomy, but from different patients. We use the statistics from the same location across different patients' images, rather than within an image, to eliminate bias fields from all of the images simultaneously. Evaluating the likelihood of a particular voxel in one patient's scan with respect to voxels in the same location in a set of other patients' scans disambiguates effects that might be due to either bias fields or anatomy. We present a variety of "two dimensional" experimental results (working with one image from each patient) showing how our method overcomes serious problems experienced by other methods. We also present preliminary results on full three-dimensional volume correction across patients. PMID- 17354731 TI - Unified statistical approach to cortical thickness analysis. AB - This paper presents a unified image processing and analysis framework for cortical thickness in characterizing a clinical population. The emphasis is placed on the development of data smoothing and analysis framework. The human brain cortex is a highly convoluted surface. Due to the convoluted non-Euclidean surface geometry, data smoothing and analysis on the cortex are inherently difficult. When measurements lie on a curved surface, it is natural to assign kernel smoothing weights based on the geodesic distance along the surface rather than the Euclidean distance. We present a new data smoothing framework that address this problem implicitly without actually computing the geodesic distance and present its statistical properties. Afterwards, the statistical inference is based on the random field theory based multiple comparison correction. As an illustration, we have applied the method in detecting the regions of abnormal cortical thickness in 16 high functioning autistic children. PMID- 17354732 TI - ZHARP: three-dimensional motion tracking from a single image plane. AB - Three-dimensional imaging and quantification of myocardial function are essential steps in the evaluation of cardiac disease. We propose a tagged magnetic resonance imaging methodology called zHARP that encodes and automatically tracks myocardial displacement in three dimensions. Unlike other motion encoding techniques, zHARP encodes both in-plane and through-plane motion in a single image plane without affecting the acquisition speed. Postprocessing unravels this encoding in order to directly track the 3-D displacement of every point within the image plane throughout an entire image sequence. Experimental results include a phantom validation experiment, which compares zHARP to phase contrast imaging, and an in vivo study of a normal human volunteer. Results demonstrate that the simultaneous extraction of in-plane and through-plane displacements from tagged images is feasible. PMID- 17354733 TI - Analysis of event-related fMRI data using diffusion maps. AB - The blood oxygen level-dependent (BOLD) signal in response to brief periods of stimulus can be detected using event-related functional magnetic resonance imaging (ER-fMRI). In this paper, we propose a new approach for the analysis of ER-fMRI data. We regard the time series as vectors in a high dimensional space (the dimension is the number of time samples). We believe that all activated times series share a common structure and all belong to a low dimensional manifold. On the other hand, we expect the background time series (after detrending) to form a cloud around the origin. We construct an embedding that reveals the organization of the data into an activated manifold and a cluster of non-activated time series. We use a graph partitioning technique-the normalized cut to find the separation between the activated manifold and the background time series. We have conducted several experiments with synthetic and in-vivo data that demonstrate the performance of our approach. PMID- 17354734 TI - Automated detection of small-size pulmonary nodules based on helical CT images. AB - A computer-aided diagnosis (CAD) system to detect small-size (from 2 mm to around 10 mm) pulmonary nodules in helical CT scans is developed. This system uses different schemes to locate juxtapleural nodules and non-pleural nodules. For juxtapleural nodules, morphological closing, thresholding and labeling are performed to obtain volumetric nodule candidates; gray level and geometric features are extracted and analyzed using a linear discriminant analysis (LDA) classifier. To locate non-pleural nodules, a discrete-time cellular neural network (DTCNN) uses local shape features which successfully capture the differences between nodules and non-nodules, especially vessels. The DTCNN was trained using genetic algorithm (GA). Testing on 17 cases with 3979 slice images showed the effectiveness of the proposed system, yielding sensitivity of 85.6% with 9.5 FPs/case (0.04 FPs/image). Moreover, the CAD system detected many nodules missed by human visual reading. This showed that the proposed CAD system acted effectively as an assistant for human experts to detect small nodules and provided a "second opinion" to human observers. PMID- 17354735 TI - Nonparametric neighborhood statistics for MRI denoising. AB - This paper presents a novel method for denoising MR images that relies on an optimal estimation, combining a likelihood model with an adaptive image prior. The method models images as random fields and exploits the properties of independent Rician noise to learn the higher-order statistics of image neighborhoods from corrupted input data. It uses these statistics as priors within a Bayesian denoising framework. This paper presents an information theoretic method for characterizing neighborhood structure using nonparametric density estimation. The formulation generalizes easily to simultaneous denoising of multimodal MRI, exploiting the relationships between modalities to further enhance performance. The method, relying on the information content of input data for noise estimation and setting important parameters, does not require significant parameter tuning. Qualitative and quantitative results on real, simulated, and multimodal data, including comparisons with other approaches, demonstrate the effectiveness of the method. PMID- 17354736 TI - Construction and validation of mean shape atlas templates for atlas-based brain image segmentation. AB - In this paper, we evaluate different schemes for constructing a mean shape anatomical atlas for atlas-based segmentation of MR brain images. Each atlas is constructed and validated using a database of 20 images for which detailed manual delineations of 49 different subcortical structures are available. Atlas construction and atlas based segmentation are performed by non-rigid intensity based registration using a viscous fluid deformation model with parameters that were optimally tuned for this particular task. The segmentation performance of each atlas scheme is evaluated on the same database using a leave-one-out approach and measured by the volume overlap of corresponding regions in the ground-truth manual segmentation and the warped atlas label image. PMID- 17354737 TI - Multi-figure anatomical objects for shape statistics. AB - Multi-figure m-reps allow us to represent and analyze a complex anatomical object by its parts, by relations among its parts, and by the object itself as a whole entity. This representation also enables us to gather either global or hierarchical statistics from a population of such objects. We propose a framework to train the statistics of multi-figure anatomical objects from real patient data. This training requires fitting multi-figure m-reps to binary characteristic images of training objects. To evaluate the fitting approach, we propose a Monte Carlo method sampling the trained statistics. It shows that our methods generate geometrically proper models that are close to the set of Monte Carlo generated target models and thus can be expected to yield similar statistics to that used for the Monte Carlo generation. PMID- 17354738 TI - The role of non-overlap in image registration. AB - Here we model the effect of non-overlapping voxels on image registration, and show that a major defect of overlap-only models--their limited capture range--can be alleviated. Theoretically, we introduce a maximum likelihood model that combines histograms of overlapping and non-overlapping voxels into a common joint distribution. The convex problem for the joint distribution is solved via iterative application of replicator equations that converge monotonically. We then focus on rigidly aligning images with unknown translation, where we present a fast FFT-based method for computing joint histograms for all relative translations of an image pair. We then apply this method to standard overlap-only information theoretic registration criteria such as mutual information as well as to our variants that exploit non-overlap. Our experimental results show that global optima correspond to the correct registration generally only when non overlapping image regions are included. PMID- 17354739 TI - Multimodality image registration using an extensible information metric and high dimensional histogramming. AB - We extend an information metric from intermodality (2-image) registration to multimodality (multiple-image) registration so that we can simultaneously register multiple images of different modalities. And we also provide the normalized version of the extensible information metric, which has better performance in high noise situations. Compared to mutual information which can even become negative in the multiple image case, our metric can be easily and naturally extended to multiple images. After using a new technique to efficiently compute high dimensional histograms, the extensible information metric can be efficiently computed even for multiple images. To showcase the new measure, we compare the results of direct multimodality registration using high-dimensional histogramming with repeated intermodality registration. We find that registering 3 images simultaneously with the new metric is more accurate than pair-wise registration on 2D images obtained from synthetic magnetic resonance (MR) proton density (PD), MR T2 and MR T1 3D volumes from Brain Web. We perform the unbiased registration of 5 multimodality images of anatomy, CT, MR PD, T1 and T2 from Visible Human Male Data with the normalized metric and high-dimensional histogramming. Our results demonstrate the efficacy of the metrics and high dimensional histogramming in affine, multimodality image registration. PMID- 17354740 TI - Spherical navigator registration using harmonic analysis for prospective motion correction. AB - Spherical navigators are an attractive approach to motion compensation in Magnetic Resonance Imaging. Because they can be acquired quickly, spherical navigators have the potential to measure and correct for rigid motion during image acquisition (prospectively as opposed to retrospectively). A limiting factor to prospective use of navigators is the time required to estimate the motion parameters. This estimation problem can be separated into a rotational and translational component. Recovery of the rotational motion can be cast as a registration of functions defined on a sphere. Previous methods for solving this registration problem are based on optimization strategies that are iterative and require k-space interpolation. Such approaches have undesirable convergence behavior for prospective use since the estimation complexity depends on both the number of samples and the amount of rotation. We propose and demonstrate an efficient algorithm for recovery of rotational motion using spherical navigators. We decompose the navigator magnitude using the spherical harmonic transform. In this framework, rigid rotations can be recovered from an over-constrained system of equations, leading to a computationally efficient algorithm for prospective motion compensation. The resulting algorithm is compared to existing approaches in simulated and actual navigator data. These results show that the spherical harmonic based estimation algorithm is significantly faster than existing methods and so is suited for prospective motion correction. PMID- 17354741 TI - Tunneling descent level set segmentation of ultrasound images. AB - The presence of speckle in ultrasound images causes many spurious local minima in the energy function of active contours. These minima trap the segmentation prematurely under gradient descent and cause the algorithm to fail. This paper presents a substantially new reformulation of Tunneling Descent, which is a deterministic technique to escape from unwanted local minima. In the new formulation, the evolving curve is represented by level sets, and the evolution strategy is obtained as a sequence of constrained minimizations. The algorithm is used to segment the endocardium in 115 short axis cardiac ultrasound images. All segmentations are achieved without tweaking the energy function or numerical parameters. Experimental evaluation of the results shows that the algorithm overcomes multiple local minima to give segmentations that are considerably more accurate than conventional techniques. PMID- 17354742 TI - Multi-object segmentation using shape particles. AB - Deformable template models, in which a shape model and its corresponding appearance model are deformed to optimally fit an object in the image, have proven successful in many medical image segmentation tasks. In some applications, the number of objects in an image is not known a priori. In that case not only the most clearly visible object must be extracted, but the full collection of objects present in the image. We propose a stochastic optimization algorithm that optimizes a distribution of shape particles so that the overall distribution explains as much of the image as possible. Possible spatial interrelationships between objects are modelled and used to steer the evolution of the particle set by generating new shape hypotheses that are consistent with the shapes currently observed. The method is evaluated on rib segmentation in chest X-rays. PMID- 17354743 TI - Medical expert witnesses can be disciplined by the GMC. PMID- 17354744 TI - Who goes there? Government, judiciary and the medical profession--friend or foe? PMID- 17354745 TI - Psychiatry and the law: uneasy bedfellows. PMID- 17354746 TI - Attention deficit hyperactivity disorder: legal and ethical issues. PMID- 17354747 TI - When does the NHS (UK government) have to pay for medical treatment in another EU state? Are patients gaining greater legal power over the secretary of state? PMID- 17354748 TI - The Compensation Act 2006: helpful or unhelpful for doctors? PMID- 17354749 TI - Robust active shape models: a robust, generic and simple automatic segmentation tool. AB - This paper presents a new segmentation algorithm which combines active shape model and robust point matching techniques. It can use any simple feature detector to extract a large number of feature points in the image. Robust point matching is then used to search for the correspondences between feature and model points while the model is being deformed along the modes of variation of the active shape model. Although the algorithm is generic, it is particularly suited for medical imaging applications where prior knowledge is available. The value of the proposed method is examined with two different medical imaging modalities (Ultrasound, MRI) and in both 2D and 3D. The experiments have shown that the proposed algorithm is immune to missing feature points and noise. It has demonstrated significant improvements when compared to RPM-TPS and ASM alone. PMID- 17354750 TI - Automatic IVUS segmentation of atherosclerotic plaque with stop & go snake. AB - Since the upturn of intravascular ultrasound (IVUS) as an imaging technique for the coronary artery system, much research has been done to simplify the complicated analysis of the resulting images. In this study, an attempt to develop an automatic tissue characterization algorithm for IVUS images was done. The first step was the extraction of texture features. The resulting feature space was used for classification, constructing a likelihood map to represent different coronary plaques. The information in this map was organized using a recently developed geodesic snake formulation, the so-called Stop & Go snake. The novelty of our study lies in this last step, as it was the first time to apply the Stop & Go snake to segment IVUS images. PMID- 17354751 TI - Prostate segmentation in 2D ultrasound images using image warping and ellipse fitting. AB - This paper presents a new algorithm for the semi-automatic segmentation of the prostate from B-mode trans-rectal ultrasound (TRUS) images. The segmentation algorithm first uses image warping to make the prostate shape elliptical. Measurement points along the prostate boundary, obtained from an edge-detector, are then used to find the best elliptical fit to the warped prostate. The final segmentation result is obtained by applying a reverse warping algorithm to the elliptical fit. This algorithm was validated using manual segmentation by an expert observer on 17 midgland, pre-operative, TRUS images. Distance-based metrics between the manual and semi-automatic contours showed a mean absolute difference of 0.67 +/- 0.18 mm, which is significantly lower than inter-observer variability. Area-based metrics showed an average sensitivity greater than 97% and average accuracy greater than 93%. The proposed algorithm was almost two times faster than manual segmentation and has potential for real-time applications. PMID- 17354752 TI - Detection of electrophysiology catheters in noisy fluoroscopy images. AB - Cardiac catheter ablation is a minimally invasive medical procedure to treat patients with heart rhythm disorders. It is useful to know the positions of the catheters and electrodes during the intervention, e.g. for the automatization of cardiac mapping. Our goal is therefore to develop a robust image analysis method that can detect the catheters in X-ray fluoroscopy images. Our method uses steerable tensor voting in combination with a catheter-specific multi-step extraction algorithm. The evaluation on clinical fluoroscopy images shows that especially the extraction of the catheter tip is successful and that the use of tensor voting accounts for a large increase in performance. PMID- 17354753 TI - Fast non local means denoising for 3D MR images. AB - One critical issue in the context of image restoration is the problem of noise removal while keeping the integrity of relevant image information. Denoising is a crucial step to increase image conspicuity and to improve the performances of all the processings needed for quantitative imaging analysis. The method proposed in this paper is based on an optimized version of the Non Local (NL) Means algorithm. This approach uses the natural redundancy of information in image to remove the noise. Tests were carried out on synthetic datasets and on real 3T MR images. The results show that the NL-means approach outperforms other classical denoising methods, such as Anisotropic Diffusion Filter and Total Variation. PMID- 17354754 TI - Active shape models for a fully automated 3D segmentation of the liver--an evaluation on clinical data. AB - This paper presents an evaluation of the performance of a three-dimensional Active Shape Model (ASM) to segment the liver in 48 clinical CT scans. The employed shape model is built from 32 samples using an optimization approach based on the minimum description length (MDL). Three different gray-value appearance models (plain intensity, gradient and normalized gradient profiles) are created to guide the search. The employed segmentation techniques are ASM search with 10 and 30 modes of variation and a deformable model coupled to a shape model with 10 modes of variation. To assess the segmentation performance, the obtained results are compared to manual segmentations with four different measures (overlap, average distance, RMS distance and ratio of deviations larger 5mm). The only appearance model delivering usable results is the normalized gradient profile. The deformable model search achieves the best results, followed by the ASM search with 30 modes. Overall, statistical shape modeling delivers very promising results for a fully automated segmentation of the liver. PMID- 17354755 TI - Patient position detection for SAR optimization in magnetic resonance imaging. AB - Although magnetic resonance imaging is considered to be non-invasive, there is at least one effect on the patient which has to be monitored: The heating which is generated by absorbed radio frequency (RF) power. It is described using the specific absorption rate (SAR). In order to obey legal limits for these SAR values, the scanner's duty cycle has to be adjusted. The limiting factor depends on the patient's position with respect to the scanner. Detection of this position allows a better adjustment of the RF power resulting in an improved scan performance and image quality. In this paper, we propose real-time methods for accurately detecting the patient's position with respect to the scanner. MR data of thirteen test persons acquired using a new "move during scan" protocol which provides low resolution MR data during the initial movement of the patient bed into the scanner, is used to validate the detection algorithm. When being integrated, our results would enable automatic SAR optimization within the usual acquisition workflow at no extra cost. PMID- 17354756 TI - Symmetric atlasing and model based segmentation: an application to the hippocampus in older adults. AB - In model-based segmentation, automated region identification is achieved via registration of novel data to a pre-determined model. The desired structure is typically generated via manual tracing within this model. When model-based segmentation is applied to human cortical data, problems arise if left-right comparisons are desired. The asymmetry of the human cortex requires that both left and right models of a structure be composed in order to effectively segment the desired structures. Paradoxically, defining a model in both hemi-spheres carries a likelihood of introducing bias to one of the structures. This paper describes a novel technique for creating a symmetric average model in which both hemispheres are equally represented and thus left-right comparison is possible. This work is an extension of that proposed by Guimond et al. Hippocampal segmentation is used as a test-case in a cohort of 118 normal eld-erly subjects and results are compared with expert manual tracing. PMID- 17354757 TI - Image diffusion using saliency bilateral filter. AB - Image diffusion can smooth away noise and small-scale structures while retaining important features, thereby enhancing the performances of many image processing algorithms such as image compression, segmentation and recognition. In this paper, we present a novel diffusion algorithm for which the filtering kernels vary according to the perceptual saliency of boundaries in the input images. The boundary saliency is estimated through a saliency measure which is generally determined by curvature changes, intensity gradient and the interaction of neighboring vectors. The connection between filtering kernels and perceptual saliency makes it possible to remove small-scale structures and preserves significant boundaries adaptively. The effectiveness of the proposed approach is validated by experiments on various medical images including the color Chinese Visible Human data set and gray MRI brain images. PMID- 17354758 TI - Data weighting for principal component noise reduction in contrast enhanced ultrasound. AB - Pulse inversion ultrasound is a mechanism for preferentially displaying contrast agent in blood vessels while suppressing signal from tissue. We seek a method for identifying and segmenting areas of the liver with similar statistically significant time intensity curves. As a first step in this process, a method of weighting Rayleigh distributed ultrasound image data before principal components analysis is presented. Simulation studies show that relative mean squared error can be reduced by 14% when the correct number of dimensions in selected. Our method is tested on an in vitro ultrasound phantom showing slightly increased error suppression, and is demonstrated on a clinical liver scan, showing decreased correlation between signals in the low intensity range. PMID- 17354759 TI - Shape filtering for false positive reduction at computed tomography colonography. AB - In this paper, we treat the problem of reducing the false positives (FP) in the automatic detection of colorectal polyps at Computer Aided Detection in Computed Tomography Colonography (CAD-CTC) as a shape-filtering task. From the extracted candidate surface, we obtain a reliable shape distribution function and analyse it in the Fourier domain and use the resulting spectral data to classify the candidate surface as belonging to a polyp or a non-polyp class. The developed shape filtering scheme is computationally efficient (takes approximately 2 seconds per dataset to detect the polyps from the colonic surface) and offers robust polyp detection with an overall false positive rate of 5.44 per dataset at a sensitivity of 100% for polyps greater than 10 mm when it was applied to standard and low dose CT data. PMID- 17354760 TI - Evaluation of texture features for analysis of ovarian follicular development. AB - We examined the echotexture in ultrasonographic images of the wall of dominant ovulatory follicles in women during natural menstrual cycles and dominant anovulatory follicles which developed in women using oral contraceptives (OC). Ovarian follicles in women are fluid-filled structures in the ovary that contain oocytes (eggs). Dominant follicles are physiologically selected for preferential development and ovulation. Statistically significant differences between the two classes of follicles were observed for two co-occurrence matrix derived texture features and two edge-frequency based texture features which allowed accurate distinction of healthy and atretic follicles of similar diameters. Trend analysis revealed consistent turning points in time series of texture features between 3 and 4 days prior to ovulation coinciding with the time at which follicles are being biologically "prepared" for ovulation. PMID- 17354761 TI - A fast method of generating pharmacokinetic maps from dynamic contrast-enhanced images of the breast. AB - A new approach to fitting pharmacokinetic models to DCE-MRI data is described. The method relies on fitting individual concentration curves to a small set of basis functions and then making use of a look up table to relate the fitting coefficients to pre-calculated pharmacokinetic parameters. This is significantly faster than traditional non-linear fitting methods. Using simulated data and assuming a Tofts model, the accuracy of this direct approach is compared to the Levenberg-Marquardt algorithm. The effect of signal to noise ratio and the number of basis functions used on the accuracy is investigated. The basis fitting approach is slightly less accurate than the traditional non-linear least squares approach but the ten-fold improvement in speed makes the new technique useful as it can be used to generate pharmacokinetic maps in a clinically acceptable timeframe. PMID- 17354762 TI - Investigating cortical variability using a generic gyral model. AB - In this paper, we present a systematic investigation of the variability of the human cortical folding using a generic gyral model (GGM). The GGM consists of a fixed number of vertices that can be registered non-linearly to an individual anatomy so that for each individual we have a clearly defined set of landmarks that is spread across the cortex. This allows us to obtain a regionalized estimation of intersubject variability. Since the GGM is stratified into different levels of depth, it also allows us to estimate variability as a function of depth. As another application of a polygonal line representation underlying the generic gyral model, we present a cortical parcellation scheme that can be used to regionalize cortical measurements. PMID- 17354763 TI - Blood flow and velocity estimation based on vessel transit time by combining 2D and 3D X-ray angiography. AB - The X-ray imaging equipment could be used to measure hemodynamic function in addition to visualizing the morphology. The parameters of specific interest are arterial blood flow and velocity. Current monoplane X-ray systems can perform 3D reconstruction of the arterial tree as well as to capture the propagation of the injected contrast agent on a sequence of 2D angiograms. We combine the 2D digital subtraction angiography sequence with the mechanically registered 3D volume of the vessel tree. From 3D vessel tree we extract each vessel and obtain its centerline and cross-section area. We get our velocity estimation from 2D sequence by comparing time-density signals measured at different ends of the projected vessel. From the average velocity and cross-section area we get the average blood flow estimate for each vessel. The algorithm described here is applied to datasets from real neuroradiological studies. PMID- 17354764 TI - Accurate airway wall estimation using phase congruency. AB - Quantitative analysis of computed tomographic (CT) images of the lungs is becoming increasingly useful in the medical and surgical management of subjects with Chronic Obstructive Pulmonary Disease (COPD). Current methods for the assessment of airway wall work well in idealized models of the airway. We propose a new method for airway wall detection based on phase congruency. This method does not rely on either a specific model of the airway or the point spread function of the scanner. Our results show that our method gives a better localization of the airway wall than "full width at a half max" and is less sensitive to different reconstruction kernels and radiation doses. PMID- 17354765 TI - Generation of curved planar reformations from magnetic resonance images of the spine. AB - We present a novel method for curved planar reformation (CPR) of spine images obtained by magnetic resonance (MR) imaging. CPR images, created via a transformation from image-based to spine-based coordinate system, follow the structural shape of the spine and allow the whole course of the curved structure to be viewed in a single image. The spine-based coordinate system is defined on the 3D spine curve and on the axial vertebral rotation, both described by polynomial models. The 3D spine curve passes through the centers of vertebral bodies, and the axial vertebral rotation determines the rotation of vertebral spinous processes around the spine. The optimal polynomial parameters are found in an optimization framework, based on image analysis. The method was evaluated on 19 MR images of the spine from 10 patients. PMID- 17354766 TI - Automated analysis of multi site MRI phantom data for the NIHPD project. AB - In large multi-center studies it is important to quantify data variations due to differences between sites and over time. Here we investigate inter-site variability in signal to noise ratio (SNR), percent integral uniformity (PIU), width and height using the American College of Radiology (ACR) phantom scans from the NIHPD project. Longitudinal variations are also analyzed. All measurements are fully automated. Our results show that the mean SNR, PIU and the 2 metric values were statistically different across sites. The maximum mean difference in diameter across sites was 2 mm (1.1%), and the maximum mean difference in height was 2.5 mm (1.7%). Over time, an average drift of 0.4 mm per year was observed for the diameter while a drift of 0.5 mm per year was observed for the height. Trends observed over time often depended not only on site, but also on modality and scanner manufacturer. PMID- 17354767 TI - Performance evaluation of grid-enabled registration algorithms using bronze standards. AB - Evaluating registration algorithms is difficult due to the lack of gold standard in most clinical procedures. The bronze standard is a real-data based statistical method providing an alternative registration reference through a computationally intensive image database registration procedure. We propose in this paper an efficient implementation of this method through a grid-interfaced workflow enactor enabling the concurrent processing of hundreds of image registrations in a couple of hours only. The performances of two different grid infrastructures were compared. We computed the accuracy of 4 different rigid registration algorithms on longitudinal MRI images of brain tumors. Results showed an average subvoxel accuracy of 0.4 mm and 0.15 degrees in rotation. PMID- 17354768 TI - Anisotropic feature extraction from endoluminal images for detection of intestinal contractions. AB - Wireless endoscopy is a very recent and at the same time unique technique allowing to visualize and study the occurrence of contractions and to analyze the intestine motility. Feature extraction is essential for getting efficient patterns to detect contractions in wireless video endoscopy of small intestine. We propose a novel method based on anisotropic image filtering and efficient statistical classification of contraction features. In particular, we apply the image gradient tensor for mining informative skeletons from the original image and a sequence of descriptors for capturing the characteristic pattern of contractions. Features extracted from the endoluminal images were evaluated in terms of their discriminatory ability in correct classifying images as either belonging to contractions or not. Classification was performed by means of a support vector machine classifier with a radial basis function kernel. Our classification rates gave sensitivity of the order of 90.84% and specificity of the order of 94.43% respectively. These preliminary results highlight the high efficiency of the selected descriptors and support the feasibility of the proposed method in assisting the automatic detection and analysis of contractions. PMID- 17354769 TI - Symmetric curvature patterns for colonic polyp detection. AB - A novel approach for generating a set of features derived from properties of patterns of curvature is introduced as a part of a computer aided colonic polyp detection system. The resulting sensitivity was 84% with 4.8 false positives per volume on an independent test set of 72 patients (56 polyps). When used in conjunction with other features, it allowed the detection system to reach an overall sensitivity of 94% with a false positive rate of 4.3 per volume. PMID- 17354770 TI - 3D reconstruction of coronary stents in vivo based on motion compensated X-ray angiograms. AB - A new method is introduce for the three-dimensional (3D) reconstruction of the coronary stents in-vivo utilizing two-dimensional projection images acquired during rotational angiography (RA). The method is based on the application of motion compensated techniques to the acquired angiograms resulting in a temporal snapshot of the stent within the cardiac cycle. For the first time results of 3D reconstructed coronary stents in vivo, with high spatial resolution are presented. The proposed method allows for a comprehensive and unique quantitative 3D assessment of stent expansion that rivals current x-ray and intravascular ultrasound techniques. PMID- 17354771 TI - Retina mosaicing using local features. AB - Laser photocoagulation is a proven procedure to treat various pathologies of the retina. Challenges such as motion compensation, correct energy dosage, and avoiding incidental damage are responsible for the still low success rate. They can be overcome with improved instrumentation, such as a fully automatic laser photocoagulation system. In this paper, we present a core image processing element of such a system, namely a novel approach for retina mosaicing. Our method relies on recent developments in region detection and feature description to automatically fuse retina images. In contrast to the state-of-the-art the proposed approach works even for retina images with no discernable vascularity. Moreover, an efficient scheme to determine the blending masks of arbitrarily overlapping images for multi-band blending is presented. PMID- 17354772 TI - A new cortical surface parcellation model and its automatic implementation. AB - In this paper, we present an original method that aims at parcellating the cortical surface in regions functionally meaningful, from individual anatomy. The parcellation is obtained using an anatomically constrained surface-based coordinate system from which we define a complete partition of the surface. The aim of our method is to exhibit a new way to describe the cortical surface organization, in both anatomical and functional terms. The method is described together with results applied to a functional somatotopy experiments. PMID- 17354773 TI - A system for measuring regional surface folding of the neonatal brain from MRI. AB - This paper describes a novel approach to in-vivo measurement of brain surface folding in clinically acquired neonatal MR image data, which allows evaluation of surface curvature within subregions of the cortex. This paper addresses two aspects of this problem. Firstly: normalization of folding measures to provide area-independent evaluation of surface folding over arbitrary subregions of the cortex. Secondly: automated parcellation of the cortex at a particular developmental stage, based on an approximate spatial normalization of previously developed anatomical boundaries. The method was applied to seven premature infants (age 28-37 weeks) from which gray matter and gray-white matter interface surfaces were extracted. Experimental results show that previous folding measures are sensitive to the size of the surface of analysis, and that the area independent measures proposed here provide significant improvements. Such a system provides a tool to allow the study of structural development in the neonatal brain within specific functional subregions, which may be critical in identifying later neurological impairment. PMID- 17354774 TI - Atlas guided identification of brain structures by combining 3D segmentation and SVM classification. AB - This study presents a novel automatic approach for the identification of anatomical brain structures in magnetic resonance images (MRI). The method combines a fast multiscale multi-channel three dimensional (3D) segmentation algorithm providing a rich feature vocabulary together with a support vector machine (SVM) based classifier. The segmentation produces a full hierarchy of segments, expressed by an irregular pyramid with only linear time complexity. The pyramid provides a rich, adaptive representation of the image, enabling detection of various anatomical structures at different scales. A key aspect of the approach is the thorough set of multiscale measures employed throughout the segmentation process which are also provided at its end for clinical analysis. These features include in particular the prior probability knowledge of anatomic structures due to the use of an MRI probabilistic atlas. An SVM classifier is trained based on this set of features to identify the brain structures. We validated the approach using a gold standard real brain MRI data set. Comparison of the results with existing algorithms displays the promise of our approach. PMID- 17354775 TI - A nonparametric bayesian approach to detecting spatial activation patterns in fMRI data. AB - Traditional techniques for statistical fMRI analysis are often based on thresholding of individual voxel values or averaging voxel values over a region of interest. In this paper we present a mixture-based response-surface technique for extracting and characterizing spatial clusters of activation patterns from fMRI data. Each mixture component models a local cluster of activated voxels with a parametric surface function. A novel aspect of our approach is the use of Bayesian nonparametric methods to automatically select the number of activation clusters in an image. We describe an MCMC sampling method to estimate both parameters for shape features and the number of local activations at the same time, and illustrate the application of the algorithm to a number of different fMRI brain images. PMID- 17354776 TI - Fast and accurate connectivity analysis between functional regions based on DT MRI. AB - Diffusion tensor and functional MRI data provide insight into function and structure of the human brain. However, connectivity analysis between functional areas is still a challenge when using traditional fiber tracking techniques. For this reason, alternative approaches incorporating the entire tensor information have emerged. Based on previous research employing pathfinding for connectivity analysis, we present a novel search grid and an improved cost function which essentially contributes to more precise paths. Additionally, implementation aspects are considered making connectivity analysis very efficient which is crucial for surgery planning. In comparison to other algorithms, the presented technique is by far faster while providing connections of comparable quality. The clinical relevance is demonstrated by reconstructed connections between motor and sensory speech areas in patients with lesions located in between. PMID- 17354777 TI - Riemannian graph diffusion for DT-MRI regularization. AB - A new method for diffusion tensor MRI (DT-MRI) regularization is presented that relies on graph diffusion. We represent a DT image using a weighted graph, where the weights of edges are functions of the geodesic distances between tensors. Diffusion across this graph with time is captured by the heat-equation, and the solution, i.e. the heat kernel, is found by exponentiating the Laplacian eigen system with time. Tensor regularization is accomplished by computing the Riemannian weighted mean using the heat kernel as its weights. The method can efficiently remove noise, while preserving the fine details of images. Experiments on synthetic and real-world datasets illustrate the effectiveness of the method. PMID- 17354778 TI - High-dimensional white matter atlas generation and group analysis. AB - We present a two-step process including white matter atlas generation and automatic segmentation. Our atlas generation method is based on population fiber clustering. We produce an atlas which contains high-dimensional descriptors of fiber bundles as well as anatomical label information. We use the atlas to automatically segment tractography in the white matter of novel subjects and we present quantitative results (FA measurements) in segmented white matter regions from a small population. We demonstrate reproducibility of these measurements across scans. In addition, we introduce the idea of using clustering for automatic matching of anatomical structures across hemispheres. PMID- 17354779 TI - Fiber bundle estimation and parameterization. AB - Individual white matter fibers cannot be resolved by current magnetic resonance (MR) technology. Many fibers of a fiber bundle will pass through an individual volume element (voxel). Individual visualized fiber tracts are thus the result of interpolation on a relatively coarse voxel grid, and an infinite number of them may be generated in a given volume by interpolation. This paper aims at creating a level set representation of a fiber bundle to describe this apparent continuum of fibers. It further introduces a coordinate system warped to the fiber bundle geometry, allowing for the definition of geometrically meaningful fiber bundle measures. PMID- 17354780 TI - Improved correspondence for DTI population studies via unbiased atlas building. AB - We present a method for automatically finding correspondence in Diffusion Tensor Imaging (DTI) from deformable registration to a common atlas. The registration jointly produces an average DTI atlas, which is unbiased with respect to the choice of a template image, along with diffeomorphic correspondence between each image. The registration image match metric uses a feature detector for thin fiber structures of white matter, and interpolation and averaging of diffusion tensors use the Riemannian symmetric space framework. The anatomically significant correspondence provides a basis for comparison of tensor features and fiber tract geometry in clinical studies and for building DTI population atlases. PMID- 17354781 TI - Diffusion k-tensor estimation from Q-ball imaging using discretized principal axes. AB - A reoccurring theme in the diffusion tensor imaging literature is the per-voxel estimation of a symmetric 3 x 3 tensor describing the measured diffusion. In this work we attempt to generalize this approach by calculating 2 or 3 or up to k diffusion tensors for each voxel. We show that our procedure can more accurately describe the diffusion particularly when crossing fibers or fiber-bundles are present in the datasets. PMID- 17354782 TI - Improved map-slice-to-volume motion correction with B0 inhomogeneity correction: validation of activation detection algorithms using ROC curve analyses. AB - Head motion is a significant source of error in fMRI activation detection and a common approach is to apply 3D volumetric rigid body motion correction techniques. However, in 2D multislice fMRI, each slice may have a distinct set of motion parameters due to inter-slice motion. Here, we apply an automated mutual information based slice-to-volume rigid body registration technique on time series data synthesized from a T2 MRI brain dataset with simulated motion, functional activation, noise and geometric distortion. The map-slice-to-volume (MSV) technique was previously applied to patient data without ground truths for motion and activation regions. In this study, the activation images and area under the receiver operating characteristic curves for various time series datasets indicate that the MSV registration improves the activation detection capability when compared to results obtained from Statistical Parametric Mapping (SPM). The effect of temporal median filtering of motion parameters on activation detection performance was also investigated. PMID- 17354783 TI - Hippocampus-specific fMRI group activation analysis with continuous M-Reps. AB - A new approach to group activation analysis in fMRI studies that test hypotheses focused on specific brain structures is presented and used to analyze hippocampal activation in a visual scene encoding study. The approach leverages the cm-rep method to normalize hippocampal anatomy and project intra-subject hippocampal activation maps into a common reference space, eliminating normalization errors inherent in whole-brain approaches and guaranteeing that peaks detected in the random effects activation map are indeed associated with the hippocampus. When applied to real fMRI data, the method detects more significant hippocampal activation than the established whole-brain method. PMID- 17354784 TI - Particle filtering for nonlinear BOLD signal analysis. AB - Functional Magnetic Resonance imaging studies analyse sequences of brain volumes whose intensity changes predominantly reflect blood oxygenation level dependent (BOLD) effects. The most comprehensive signal model to date of the BOLD effect is formulated as a continuous-time system of nonlinear stochastic differential equations. In this paper we present a particle filtering method for the analysis of the BOLD system, and demonstrate it to be both accurate and robust in estimating the hidden physiological states including cerebral blood flow, cerebral blood volume, total deoxyhemoglobin content, and the flow inducing signal, from functional imaging data. PMID- 17354785 TI - Anatomically informed convolution kernels for the projection of fMRI data on the cortical surface. AB - We present here a method that aims at producing representations of functional brain data on the cortical surface from functional MRI volumes. Such representations are required for subsequent cortical-based functional analysis. We propose a projection technique based on the definition, around each node of the grey/white matter interface mesh, of convolution kernels whose shape and distribution rely on the geometry of the local anatomy. For one anatomy, a set of convolution kernels is computed that can be used to project any functional data registered with this anatomy. The method is presented together with experiments on synthetic data and real statistical t-maps. PMID- 17354786 TI - A landmark-based brain conformal parametrization with automatic landmark tracking technique. AB - In this paper, we present algorithms to automatically detect and match landmark curves on cortical surfaces to get an optimized brain conformal parametrization. First, we propose an automatic landmark curve tracing method based on the principal directions of the local Weingarten matrix. Our algorithm obtains a hypothesized landmark curves using the Chan-Vese segmentation method, which solves a Partial Differential Equation (PDE) on a manifold with global conformal parameterization. Based on the global conformal parametrization of a cortical surface, our method adjusts the landmark curves iteratively on the spherical or rectangular parameter domain of the cortical surface along its principal direction field, using umbilic points of the surface as anchors. The landmark curves can then be mapped back onto the cortical surface. Experimental results show that the landmark curves detected by our algorithm closely resemble these manually labeled curves. Next, we applied these automatically labeled landmark curves to generate an optimized conformal parametrization of the cortical surface, in the sense that homologous features across subjects are caused to lie at the same parameter locations in a conformal grid. Experimental results show that our method can effectively help in automatically matching cortical surfaces across subjects. PMID- 17354787 TI - Automated topology correction for human brain segmentation. AB - We describe a new method to reconstruct human brain structures from 3D magnetic resonance brain images. Our method provides a fully automatic topology correction mechanism, thus avoiding tedious manual correction. Topological correctness is important because it is an essential prerequisite for brain atlas deformation and surface flattening. Our method uses an axis-aligned sweep through the volume to locate handles. Handles are detected by successively constructing and analyzing a directed graph. A multiple local region-growing process is used which simultaneously acts on the foreground and the background to isolate handles and tunnels. The sizes of handles and tunnels are measured, then handles are removed or tunnels filled based on their sizes. This process was used for 256 T1-weighted MR volumes. PMID- 17354788 TI - A fast and automatic method to correct intensity inhomogeneity in MR brain images. AB - This paper presents a method to improve the semi-automatic method for intensity inhomogeneity correction by Dawant et al. through introducing a fully automatic approach to reference points generation, which is based on order statistics and integrates information from the fine to coarse scale representations of the input image. The method has been validated and compared with two popular methods, N3 and BFC. Advantages of the proposed method are demonstrated. PMID- 17354789 TI - A digital pediatric brain structure atlas from T1-weighted MR images. AB - Human brain atlases are indispensable tools in model-based segmentation and quantitative analysis of brain structures. However, adult brain atlases do not adequately represent the normal maturational patterns of the pediatric brain, and the use of an adult model in pediatric studies may introduce substantial bias. Therefore, we proposed to develop a digital atlas of the pediatric human brain in this study. The atlas was constructed from T1-weighted MR data set of a 9-year old, right-handed girl. Furthermore, we extracted and simplified boundary surfaces of 25 manually defined brain structures (cortical and subcortical) based on surface curvature. We constructed a 3D triangular mesh model for each structure by triangulation of the structure's reference points. Kappa statistics (cortical, 0.97; subcortical, 0.91) indicated substantial similarities between the mesh-defined and the original volumes. Our brain atlas and structural mesh models (www.stjude.org/brainatlas) can be used to plan treatment, to conduct knowledge and model-driven segmentation, and to analyze the shapes of brain structures in pediatric patients. PMID- 17354790 TI - Discriminative analysis of early Alzheimer's disease based on two intrinsically anti-correlated networks with resting-state fMRI. AB - In this work, we proposed a discriminative model of Alzheimer's disease (AD) on the basis of multivariate pattern classification and functional magnetic resonance imaging (fMRI). This model used the correlation/anti-correlation coefficients of two intrinsically anti-correlated networks in resting brains, which have been suggested by two recent studies, as the feature of classification. Pseudo-Fisher Linear Discriminative Analysis (pFLDA) was then performed on the feature space and a linear classifier was generated. Using leave one-out (LOO) cross validation, our results showed a correct classification rate of 83%. We also compared the proposed model with another one based on the whole brain functional connectivity. Our proposed model outperformed the other one significantly, and this implied that the two intrinsically anti-correlated networks may be a more susceptible part of the whole brain network in the early stage of AD. PMID- 17354791 TI - Rawdata-based detection of the optimal reconstruction phase in ECG-gated cardiac image reconstruction. AB - In order to achieve diagnostically useful CT (computed tomography) images of the moving heart, the standard image reconstruction has to be modified to a phase correlated reconstruction, which considers the motion phase of the heart and generates a quasi-static image in one defined motion phase. For that purpose a synchronization signal is needed, typically a concurrent ECG recording. Commonly, the reconstruction phase is adapted by the user to the patient-specific heart motion to improve the image quality and thus the diagnostic value. The purpose of our work is to automatically identify the optimal reconstruction phase for cardiac CT imaging with respect to motion artifacts. We provide a solution for a patient- and heart rate-independent detection of the optimal phase in the cardiac cycle which shows a minimum of cardiac movement. We validated our method by the correlation with the reconstruction phase selected visually on the basis of ECG triggering and used for the medical diagnosis. The mean difference between both reconstruction phases was 12.5% with respect to a whole cardiac motion cycle indicating a high correlation. Additionally, reconstructed cardiac images are shown which confirm the results expressed by the correlation measurement and in some cases even indicating an improvement using the proposed method. PMID- 17354792 TI - Sensorless reconstruction of freehand 3D ultrasound data. AB - Freehand 3D ultrasound can be acquired without a position sensor by finding the separations of pairs of frames using information in the images themselves. Previous work has not considered how to reconstruct entirely freehand data, which can exhibit irregularly spaced frames, non-monotonic out-of-plane probe motion and significant inplane motion. This paper presents reconstruction methods that overcome these limitations and are able to robustly reconstruct freehand data. The methods are assessed on freehand data sets and compared to reconstructions obtained using a position sensor. PMID- 17354793 TI - Motion-compensated MR valve imaging with COMB tag tracking and super-resolution enhancement. AB - MR imaging of the heart valve leaflets is a challenging problem due to their large movements throughout the cardiac cycle. This paper presents a motion compensated imaging approach with COMB tagging for valve imaging. It involves an automatic method for tracking the full 3D motion of the valve plane so as to provide a motion-tracked acquisition scheme. Super-resolution enhancement is then applied to the slice-select direction so that the partial volume effect is minimised. In vivo results have shown that in terms of slice positioning, the method has equivalent accuracy to that of a manual approach whilst being quicker and more consistent. The use of multiple parallel COMB tags will permit adaptive imaging that follows tissue motion. This will have significant implications for quantification of myocardial perfusion and tracking anatomy, functions that are traditionally difficult in MRI. PMID- 17354794 TI - Recovery of liver motion and deformation due to respiration using laparoscopic freehand 3D ultrasound system. AB - This paper describes a rapid method for intraoperative recovery of liver motion and deformation due to respiration by using a laparoscopic freehand 3D ultrasound (US) system. Using the proposed method, 3D US images of the liver can be extended to 4D US images by acquiring additional several sequences of 2D US images during a couple of respiration cycles. Time-varying 2D US images are acquired on several sagittal image planes and their 3D positions and orientations are measured using a laparoscopic ultrasound probe to which a miniature magnetic 3D position sensor is attached. During the acquisition, the probe is assumed to move together with the liver surface. In-plane 2D deformation fields and respiratory phase are estimated from the time-varying 2D US images, and then the time-varying 3D deformation fields on the sagittal image planes are obtained by combining 3D positions and orientations of the image planes. The time-varying 3D deformation field of the volume is obtained by interpolating the 3D deformation fields estimated on several planes. The proposed method was evaluated by in vivo experiments using a pig liver. PMID- 17354795 TI - Numerical simulation of radio frequency ablation with state dependent material parameters in three space dimensions. AB - We present a model for the numerical simulation of radio frequency (RF) ablation of tumors with mono- or bipolar probes. This model includes the electrostatic equation and a variant of the well-known bio-heat transfer equation for the distribution of the electric potential and the induced heat. The equations are nonlinearly coupled by material parameters that change with temperature, dehydration and damage of the tissue. A fixed point iteration scheme for the nonlinear model and the spatial discretization with finite elements are presented. Moreover, we incorporate the effect of evaporation of water from the cells at high temperatures using a predictor-corrector like approach. The comparison of the approach to a real ablation concludes the paper. PMID- 17354796 TI - Towards a multi-modal atlas for neurosurgical planning. AB - Digital brain atlases can be used in conjuction with magnetic resonance imaging (MRI) and computed tomography (CT) for planning and guidance during neurosurgery. Digital atlases are advantageous since they can be warped nonlinearly to fit each patient's unique anatomy. Functional neurosurgery with implantation of deep brain stimulating (DBS) electrodes requires accurate targeting, and has become a popular surgical technique in Parkinsonian patients. In this paper, we present a method for integrating postoperative data from subthalamic (STN) DBS implantation into an antomical atlas of the basal ganglia and thalamus. The method estimates electrode position from post-operative magnetic resonance imaging (MRI) data. These electrodes are then warped back into the atlas space and are modelled in three dimensions. The average of these models is then taken to show the region where the majority of STN DBS electrodes were implanted. The group with more favorable post-operative results was separated from the group which responded to the STN DBS implantation procedure less favourably to create a probablisitic distribution of DBS in the STN electrodes. PMID- 17354797 TI - Using registration uncertainty visualization in a user study of a simple surgical task. AB - We present a novel method to visualize registration uncertainty and a simple study to motivate the use of uncertainty visualization in computer-assisted surgery. Our visualization method resulted in a statistically significant reduction in the number of attempts required to localize a target, and a statistically significant reduction in the number of targets that our subjects failed to localize. Most notably, our work addresses the existence of uncertainty in guidance and offers a first step towards helping surgeons make informed decisions in the presence of imperfect data. PMID- 17354798 TI - Ultrasound monitoring of tissue ablation via deformation model and shape priors. AB - A rapid approach to monitor ablative therapy through optimizing shape and elasticity parameters is introduced. Our motivating clinical application is targeting and intraoperative monitoring of hepatic tumor thermal ablation, but the method translates to the generic problem of encapsulated stiff masses (solid organs, tumors, ablated lesions, etc.) in ultrasound imaging. The approach involves the integration of the following components: a biomechanical computational model of the tissue, a correlation approach to estimate/track tissue deformation, and an optimization method to solve the inverse problem and recover the shape parameters in the volume of interest. Successful convergence and reliability studies were conducted on simulated data. Then ex-vivo studies were performed on 18 ex-vivo bovine liver samples previously ablated under ultrasound monitoring in controlled laboratory environment. While B-mode ultrasound does not clearly identify the development of necrotic lesions, the proposed technique can potentially segment the ablation zone. The same framework can also yield both partial and full elasticity reconstruction. PMID- 17354799 TI - Assessment of airway remodeling in asthma: volumetric versus surface quantification approaches. AB - This paper develops a volumetric quantification approach of the airway wall in multi-detector computed tomography (MDCT), exploiting a 3D segmentation methodology based on patient-specific deformable mesh model. A comparative study carried out with respect to a reference 2D/3D surface quantification technique underlines the clinical interest of the proposed approach in assessing airway remodeling in asthmatics and in evaluating the efficiency of therapeutic protocols. PMID- 17354800 TI - Asymmetry of SPECT perfusion image patterns as a diagnostic feature for Alzheimer's disease. AB - In this paper we propose a new diagnostic feature for Alzheimer's Disease (AD) which is based on assessment of the degree of inter-hemispheric asymmetry using Single Photon Emission Computed Tomography (SPECT). The asymmetry measure used represents differences in 3D perfusion image patterns in the cerebral hemispheres. We start from the simplest descriptors of brain perfusion such as the mean intensity within pairs of brain lobes, gradually increasing the resolution up to five-dimensional co-occurrence matrices. Evaluation of the method was performed using SPECT scans of 79 subjects including 42 patients with clinical diagnosis of AD and 37 controls. It was found that combination of intensity and gradient features in co-occurrence matrices captures significant differences in asymmetry values between AD and normal controls (p < 0.00003 for all cerebral lobes). Our results suggest that the asymmetry feature is useful for discriminating AD patients from normal controls as detected by SPECT. PMID- 17354801 TI - Predicting the effects of deep brain stimulation with diffusion tensor based electric field models. AB - Deep brain stimulation (DBS) is an established therapy for the treatment of movement disorders, and has shown promising results for the treatment of a wide range of other neurological disorders. However, little is known about the mechanism of action of DBS or the volume of brain tissue affected by stimulation. We have developed methods that use anatomical and diffusion tensor MRI (DTI) data to predict the volume of tissue activated (VTA) during DBS. We co-register the imaging data with detailed finite element models of the brain and stimulating electrode to enable anatomically and electrically accurate predictions of the spread of stimulation. One critical component of the model is the DTI tensor field that is used to represent the 3-dimensionally anisotropic and inhomogeneous tissue conductivity. With this system we are able to fuse structural and functional information to study a relevant clinical problem: DBS of the subthalamic nucleus for the treatment of Parkinsons disease (PD). Our results show that inclusion of the tensor field in our model caused significant differences in the size and shape of the VTA when compared to a homogeneous, isotropic tissue volume. The magnitude of these differences was proportional to the stimulation voltage. Our model predictions are validated by comparing spread of predicted activation to observed effects of oculomotor nerve stimulation in a PD patient. In turn, the 3D tissue electrical properties of the brain play an important role in regulating the spread of neural activation generated by DBS. PMID- 17354802 TI - CFD analysis incorporating the influence of wall motion: application to intracranial aneurysms. AB - Haemodynamics, and in particular wall shear stress, is thought to play a critical role in the progression and rupture of intracranial aneurysms. A novel method is presented that combines image-based wall motion estimation obtained through non rigid registration with computational fluid dynamics (CFD) simulations in order to provide realistic intra-aneurysmal flow patterns and understand the effects of deforming walls on the haemodynamic patterns. In contrast to previous approaches, which assume rigid walls or ad hoc elastic parameters to perform the CFD simulations, wall compliance has been included in this study through the imposition of measured wall motions. This circumvents the difficulties in estimating personalized elasticity properties. Although variations in the aneurysmal haemodynamics were observed when incorporating the wall motion, the overall characteristics of the wall shear stress distribution do not seem to change considerably. Further experiments with more cases will be required to establish the clinical significance of the observed variations. PMID- 17354803 TI - A new CAD system for the evaluation of kidney diseases using DCE-MRI. AB - Acute rejection is the most common reason of graft failure after kidney transplantation, and early detection is crucial to survive the transplanted kidney function. In this paper, we introduce a new approach for the automatic classification of normal and acute rejection transplants from Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI). The proposed algorithm consists of three main steps; the first step isolates the kidney from the surrounding anatomical structures by evolving a deformable model based on two density functions; the first function describes the distribution of the gray level inside and outside the kidney region and the second function describes the prior shape of the kidney. In the second step, a new nonrigid registration approach is employed to account for the motion of the kidney due to patient breathing. To validate our registration approach, we use a simulation of deformations based on biomechanical modelling of the kidney tissue using the finite element method (F.E.M.). Finally, the perfusion curves that show the transportation of the contrast agent into the tissue are obtained from the cortex and used in the classification of normal and acute rejection transplants. Applications of the proposed approach yield promising results that would, in the near future, replace the use of current technologies such as nuclear imaging and ultrasonography, which are not specific enough to determine the type of kidney dysfunction. PMID- 17354804 TI - Generation and application of a probabilistic breast cancer atlas. AB - Computer-aided detection (CAD) has become increasingly common in recent years as a tool in catching breast cancer in its early, more treatable stages. More and more breast centers are using CAD as studies continue to demonstrate its effectiveness. As the technology behind CAD improves, so do its results and its impact on society. In trying to improve the sensitivity and specificity of CAD algorithms, a good deal of work has been done on feature extraction, the generation of mathematical representations of mammographic features which can help distinguish true cancerous lesions from false ones. One feature that is not currently seen in the literature that physicians rely on in making their decisions is location within the breast. This is a difficult feature to calculate as it requires a good deal of prior knowledge as well as some way of accounting for the tremendous variability present in breast shapes. In this paper, we present a method for the generation and implementation of a probabilistic breast cancer atlas. We then validate this method on data from the Digital Database for Screening Mammography (DDSM). PMID- 17354805 TI - Hierarchical part-based detection of 3D flexible tubes: application to CT colonoscopy. AB - In this paper, we present a learning-based method for the detection and segmentation of 3D free-form tubular structures, such as the rectal tubes in CT colonoscopy. This method can be used to reduce the false alarms introduced by rectal tubes in current polyp detection algorithms. The method is hierarchical, detecting parts of the tube in increasing order of complexity, from tube cross sections and tube segments to the whole flexible tube. To increase the speed of the algorithm, candidate parts are generated using a voting strategy. The detected tube segments are combined into a flexible tube using a dynamic programming algorithm. Testing the algorithm on 210 unseen datasets resulted in a tube detection rate of 94.7% and 0.12 false alarms per volume. The method can be easily retrained to detect and segment other tubular 3D structures. PMID- 17354806 TI - Detection of protrusions in curved folded surfaces applied to automated polyp detection in CT colonography. AB - Over the past years many computer aided diagnosis (CAD) schemes have been presented for the detection of colonic polyps in CT Colonography. The vast majority of these methods (implicitly) model polyps as approximately spherical protrusions. Polyp shape and size varies greatly, however and is often far from spherical. We propose a shape and size invariant method to detect suspicious regions. The method works by locally deforming the colon surface until the second principal curvature is smaller than or equal to zero. The amount of deformation is a quantitative measure of the 'protrudeness'. The deformation field allows for the computation of various additional features to be used in supervised pattern recognition. It is shown how only a few features are needed to achieve 95% sensitivity at 10 false positives (FP) per dataset for polyps larger than 6 mm. PMID- 17354807 TI - Part-based local shape models for colon polyp detection. AB - This paper presents a model-based technique for lesion detection in colon CT scans that uses analytical shape models to map the local shape curvature at individual voxels to anatomical labels. Local intensity profiles and curvature information have been previously used for discriminating between simple geometric shapes such as spherical and cylindrical structures. This paper introduces novel analytical shape models for colon-specific anatomy, viz. folds and polyps, built by combining parts with simpler geometric shapes. The models better approximate the actual shapes of relevant anatomical structures while allowing the application of model-based analysis on the simpler model parts. All parameters are derived from the analytical models, resulting in a simple voxel labeling scheme for classifying individual voxels in a CT volume. The algorithm's performance is evaluated against expert-determined ground truth on a database of 42 scans and performance is quantified by free-response receiver-operator curves. PMID- 17354808 TI - An analysis of early studies released by the Lung Imaging Database Consortium (LIDC). AB - Lung cancer remains an ongoing problem resulting in substantial deaths in the United States and the world. Within the United states, cancer of the lung and bronchus are the leading causes of fatal malignancy and make up 32% of the cancer deaths among men and 25% of the cancer deaths among women. Five year survival is low, (14%), but recent studies are beginning to provide some hope that we can increase survivability of lung cancer provided that the cancer is caught and treated in early stages. These results motivate revisiting the concept of lung cancer screening using thin slice multidetector computed tomography (MDCT) protocols and automated detection algorithms to facilitate early detection. In this environment, resources to aid Computer Aided Detection (CAD) researchers to rapidly develop and harden detection and diagnostic algorithms may have a significant impact on world health. The National Cancer Institute (NCI) formed the Lung Imaging Database Consortium (LIDC) to establish a resource for detecting, sizing, and characterizing lung nodules. This resource consists of multiple CT chest exams containing lung nodules that seveal radiologists manually countoured and characterized. Consensus on the location of the nodule boundaries, or even on the existence of a nodule at a particular location in the lung was not enforced, and each contour is considered a possible nodule. The researcher is encouraged to develop measures of ground truth to reconcile the multiple radiologist marks. This paper analyzes these marks to determine radiologist agreement and to apply statistical tools to the generation of a nodule ground truth. Features of the resulting consensus and individual markings are analyzed. PMID- 17354809 TI - Detecting acromegaly: screening for disease with a morphable model. AB - Acromegaly is a rare disorder which affects about 50 of every million people. The disease typically causes swelling of the hands, feet, and face, and eventually permanent changes to areas such as the jaw, brow ridge, and cheek bones. The disease is often missed by physicians and progresses beyond where it might if it were identified and treated earlier. We consider a semi-automated approach to detecting acromegaly, using a novel combination of support vector machines (SVMs) and a morphable model. Our training set consists of 24 frontal photographs of acromegalic patients and 25 of disease-free subjects. We modelled each subject's face in an analysis-by-synthesis loop using the three-dimensional morphable face model of Blanz and Vetter. The model parameters capture many features of the 3D shape of the subject's head from just a single photograph, and are used directly for classification. We report encouraging results of a classifier built from the training set of real human subjects. PMID- 17354810 TI - A boosting cascade for automated detection of prostate cancer from digitized histology. AB - Current diagnosis of prostatic adenocarcinoma is done by manual analysis of biopsy tissue samples for tumor presence. However, the recent advent of whole slide digital scanners has made histopathological tissue specimens amenable to computer-aided diagnosis (CAD). In this paper, we present a CAD system to assist pathologists by automatically detecting prostate cancer from digitized images of prostate histological specimens. Automated diagnosis on very large high resolution images is done via a multi-resolution scheme similar to the manner in which a pathologist isolates regions of interest on a glass slide. Nearly 600 image texture features are extracted and used to perform pixel-wise Bayesian classification at each image scale to obtain corresponding likelihood scenes. Starting at the lowest scale, we apply the AdaBoost algorithm to combine the most discriminating features, and we analyze only pixels with a high combined probability of malignancy at subsequent higher scales. The system was evaluated on 22 studies by comparing the CAD result to a pathologist's manual segmentation of cancer (which served as ground truth) and found to have an overall accuracy of 88%. Our results show that (1) CAD detection sensitivity remains consistently high across image scales while CAD specificity increases with higher scales, (2) the method is robust to choice of training samples, and (3) the multi-scale cascaded approach results in significant savings in computational time. PMID- 17354811 TI - Optimal sensor placement for predictive cardiac motion modeling. AB - Subject-specific physiological motion modeling combined with low-dimensional real time sensing can provide effective prediction of acyclic tissue deformation particularly due to respiration. However, real-time sensing signals used for predictive motion modeling can be strongly coupled with each other but poorly correlated with respiratory induced cardiac deformation. This paper explores a systematic framework based on sequential feature selection for optimal sensor placement so as to achieve maximal model sensitivity and prediction accuracy in response to the entire range of tissue deformation. The proposed framework effectively resolves the problem encountered by traditional regression methods in that the latent variables from both the input and output of the regression model are used to establish their inner relationships. Detailed numerical analysis and in vivo results are provided, which demonstrate the potential clinical value of the technique. PMID- 17354812 TI - 4D shape registration for dynamic electrophysiological cardiac mapping. AB - Registration of 3D segmented cardiac images with tracked electrophysiological data has been previously investigated for use in cardiac mapping and navigation systems. However, dynamic cardiac 4D (3D + time) registration methods do not presently exist. This paper introduces two new 4D registration methods based on the popular iterative closest point (ICP) algorithm that may be applied to dynamic 3D shapes. The first method averages the transformations of the 3D ICP on each phase of the dynamic data, while the second finds the closest point pairs for the data in each phase and performs a least squares fit between all the pairs combined. Experimental results show these methods yield more accurate transformations compared to using a traditional 3D approach (4D errors: Translation 0.4mm, Rotation 0.45 degrees vs. 3D errors: Translation 1.2mm, Rotation 1.3 degrees) while also increasing capture range and success PMID- 17354813 TI - Estimation of cardiac electrical propagation from medical image sequence. AB - A novel strategy is presented to recover cardiac electrical excitation pattern from tomographic medical image sequences. The geometrical/physical representation of the heart and the dense motion field of the myocardium are first derived from imaging data through segmentation and motion recovery. The myocardial active forces are then calculated through the law of force equilibrium from the motion field, realized with a stochastic multiframe algorithm. Since tissue active forces are physiologically driven by electrical excitations, we can readily relate the pattern of active forces to the pattern of electrical propagation in myocardium, where spatial regularization is enforced. Experiments are conducted on three-dimensional synthetic data and canine magnetic resonance image sequence with favorable results. PMID- 17354814 TI - Ultrasound-guided percutaneous scaphoid pinning: operator variability and comparison with traditional fluoroscopic procedure. AB - This paper reports on pilot laboratory experiments with a recently proposed surgical procedure for percutaneous screw insertion into fractured scaphoid bones using ultrasound guidance. The experiments were intended to determine the operator variability of the procedure and its performance in comparison with a traditional pinning procedure using fluoroscopy. In the proposed procedure, a three-dimensional surface model is created from pre-operative computed tomography images and intra-operatively registered to the patient using ultrasound images. A graphical interface that communicates with an optical camera tracking the surgical tools, guides the surgeon during the procedure in real time. The results of the experiments revealed non-significant differences between operators for the error in the entry location of the drill hole (p=0.90); however, significant differences for the exit location (p<0.05). Comparison with the traditional pinning procedure shows that the outcome of the recently proposed procedure appears to be more consistent. PMID- 17354815 TI - Cosmology inspired design of biomimetic tissue engineering templates with Gaussian random fields. AB - Tissue engineering integrates the principles of engineering and life sciences toward the design, construction, modification and growth of biological substitutes that restore, maintain, or improve tissue function. The structural integrity and ultimate functionality of such tissue analogs is defined by scaffolds- porous, three-dimensional "trellis-like" structures that, on implantation, provide a viable environment to regenerate damaged tissues. The orthogonal scaffold fabrication methods currently employed can be broadly classified into two categories: (a) conventional, irreproducible, stochastic techniques producing reasonably biomorphic scaffold architecture, and (b) rapidly emerging, repeatable, computer-controlled techniques producing straight edged "contra naturam" scaffold architecture. In this paper, we present the results of the first attempt in an image-based scaffold modeling and optimization strategy that synergistically exploits the orthogonal fabrication techniques to create repeatable, biomorphic scaffolds with optimal scaffold morphology. Motivated by the use of Gaussian random fields (GRF) to model cosmological structure formation, we use appropriately ordered and clipped stacks of GRF to model the three-dimensional pore-solid scaffold labyrinths. Image-based metrology, fabrication and mechanical characterization of these scaffolds reveal the possibility of enabling the previously elusive deployment of promising benchside tissue analogs to the clinical bedside. PMID- 17354816 TI - Registration of microscopic iris image sequences using probabilistic mesh. AB - This paper explores the use of deformable mesh for registration of microscopic iris image sequences. The registration, as an effort for stabilizing and rectifying images corrupted by motion artifacts, is a crucial step toward leukocyte tracking and motion characterization for the study of immune systems. The image sequences are characterized by locally nonlinear deformations, where an accurate analytical expression can not be derived through modeling of image formation. We generalize the existing deformable mesh and formulate it in a probabilistic framework, which allows us to conveniently introduce local image similarity measures, to model image dynamics and to maintain a well-defined mesh structure and smooth deformation through appropriate regularization. Experimental results demonstrate the effectiveness and accuracy of the algorithm. PMID- 17354817 TI - Tumor therapeutic response and vessel tortuosity: preliminary report in metastatic breast cancer. AB - No current non-invasive method is capable of assessing the efficacy of brain tumor therapy early during treatment. We outline an approach that evaluates tumor activity via statistical analysis of vessel shape using vessels segmented from MRA. This report is the first to describe the changes in vessel shape that occur during treatment of metastatic brain tumors as assessed by sequential MRA. In this preliminary study of 16 patients undergoing treatment for metastatic breast cancer we conclude that vessel shape may predict tumor response several months in advance of traditional methods. PMID- 17354818 TI - Harvesting the thermal cardiac pulse signal. AB - In the present paper, we propose a new pulse measurement methodology based on thermal imaging (contact-free). The method capitalizes both on the thermal undulation produced by the traveling pulse as well as the periodic expansion of the compliant vessel wall. The paper reports experiments on 34 subjects, where it compares the performance of the new pulse measurement method to the one we reported previously. The measurements were ground-truthed through a piezo electric sensor. Statistical analysis reveals that the new imaging methodology is more accurate and robust than the previous one. Its performance becomes nearly perfect, when the vessel is not obstructed by a thick fat deposit. PMID- 17354819 TI - On mobility analysis of functional sites from time lapse microscopic image sequences of living cell nucleus. AB - Recent research in biology has indicated correlations between the movement patterns of functional sites (such as replication sites in DNA) and zones of genetic activity within a nucleus. A detailed study and analysis of the motion dynamics of these sites can reveal an interesting insight into their role in DNA replication and function. In this paper, we propose a suite of novel techniques to determine, analyze, and interpret the mobility patterns of functional sites. Our algorithms are based on interesting ideas from theoretical computer science and database theory and provide for the first time the tools to interpret the seemingly stochastic motion patterns of the functional sites within the nucleus in terms of a set of tractable 'patterns' which can then be analyzed to understand their biological significance. PMID- 17354820 TI - Tissue characterization using dimensionality reduction and fluorescence imaging. AB - Multidimensional fluorescence imaging is a powerful molecular imaging modality that is emerging as an important tool in the study of biological tissues. Due to the large volume of multi-spectral data associated with the technique, it is often difficult to find the best combination of parameters to maximize the contrast between different tissue types. This paper presents a novel framework for the characterization of tissue compositions based on the use of time resolved fluorescence imaging without the explicit modeling of the decays. The composition is characterized through soft clustering based on manifold embedding for reducing the dimensionality of the datasets and obtaining a consistent differentiation scheme for determining intrinsic constituents of the tissue. The proposed technique has the benefit of being fully automatic, which could have significant advantages for automated histopathology and increasing the speed of intraoperative decisions. Validation of the technique is carried out with both phantom data and tissue samples of the human pancreas. PMID- 17354822 TI - A high-order solution for the distribution of target registration error in rigid body point-based registration. AB - Rigid registration of pre-operative surgical plans to intraoperative coordinates of a patient is an important step in computer-assisted orthopaedic surgery. A good measure for registration accuracy is the target registration error (TRE) which is the distance after registration between a pair of corresponding points not used in the registration process. However, TRE is not a deterministic value, since there is always error in the localized features (points) utilized in the registration. In this situation, the distribution of TRE carries more information than TRE by itself. Previously, the distribution of TRE has been estimated with the accuracy of the first-order approximation. In this paper, we analytically approximate the TRE distribution up to at least the second-order accuracy based on the Unscented Kalman Filter algorithm. PMID- 17354821 TI - A method for registering diffusion weighted magnetic resonance images. AB - Diffusion weighted magnetic resonance (DWMR or DW) imaging is a fast evolving technique to investigate the connectivity of brain white matter by measuring the self-diffusion of the water molecules in the tissue. Registration is a key step in group analysis of the DW images that may lead to understanding of functional and structural variability of the normal brain, understanding disease process, and improving neurosurgical planning. In this paper, we present a new method for registering DW images. The method works directly on the diffusion weighted images without using tensor reconstruction, fiber tracking, and fiber clustering. Therefore, the performance of the method does not rely on the accuracy and robustness of these steps. Moreover, since all the information in the original diffusion weighted images is used for registration, the results of the method is robust to imaging noise. We demonstrate the method on intra-subject registration with an affine transform using DW images acquired on the same scanner with the same imaging protocol. Extension to deformable registration for images acquired on different scanners and/or with different imaging protocols is also discussed. PMID- 17354823 TI - Fast elastic registration for adaptive radiotherapy. AB - A new method for elastic mono-modal image registration for adaptive fractionated radiotherapy is presented. Elastic registration is a prerequisite for many medical applications in diagnosis, therapy planning, and therapy. Especially for adaptive radiotherapy efficient and accurate registration is required. Therefore, we developed a fast block matching algorithm for robust image registration. Anatomical landmarks are automatically selected at tissue borders and relocated in the frequency domain. A smooth interpolation is calculated by modified thin plate splines with local impact. The concept of the algorithm allows different handling of different image structures. Thus, more features were included, like handling of discontinuities (e. g. air cavities in the intestinal track or rectum, observable in only one image), which can not be registered in a conventional way. The planning CT as well as delineated structures of target volume and organs at risks are transformed according to deviations observed in daily acquired verification CTs prior each dose fraction. This way, the time consuming repeated delineation, a prerequisite for adaptive radiotherapy, is avoided. The total calculation time is below 5 minutes and the accurateness is higher than voxel precision, which allows to use this tool in the clinical workflow. We present results of prostate, head-and-neck, and paraspinal tumors with verification by manually selected landmarks. We think this registration technique is not only suitable for adaptive radiotherapy, but also for other applications which require fast registration and possibilities to process special structures (e. g. discontinuities) in a different way. PMID- 17354824 TI - Registering histological and MR images of prostate for image-based cancer detection. AB - This paper presents a deformable registration method to co-register histological images with MR images of the same prostate. By considering various distortion and cutting artifacts in histological images and also fundamentally different nature of histological and MR images, our registration method is thus guided by two types of landmark points that can be reliably detected in both histological and MR images, i.e., prostate boundary points, and internal salient points that can be identified by a scale-space analysis method. The similarity between these automatically detected landmarks in histological and MR images are defined by geometric features and normalized mutual information, respectively. By optimizing a function, which integrates the similarities between landmarks with spatial constraints, the correspondences between the landmarks as well as the deformable transformation between histological and MR images can be simultaneously obtained. The performance of our proposed registration algorithm has been evaluated by various designed experiments. This work is part of a larger effort to develop statistical atlases of prostate cancer using both imaging and histological information, and to use these atlases for optimal biopsy and therapy planning. PMID- 17354825 TI - Affine registration of diffusion tensor MR images. AB - We present a new algorithm for affine registration of diffusion tensor magnetic resonance (DT-MR) images. The method is based on a new formulation of a point wise tensor similarity measure, which weights directional and magnitude information differently depending on the type of diffusion. The method is compared to a reference method, which uses normalized mutual information (NMI), calculated either from a fractional anisotropy (FA) map or a T2-weighted MR image. The registration methods are applied to real and simulated DT-MR images. Visual assessment is done for real data and for simulated data, registration accuracy is defined. The results show that the proposed method outperforms the reference method. PMID- 17354826 TI - Analytic expressions for fiducial and surface target registration error. AB - We propose and test analytic equations for approximating expected fiducial and surface target registration error (TRE). The equations are derived from a spatial stiffness model of registration. The fiducial TRE equation is equivalent to one presented by. We believe that the surface TRE equation is novel, and we provide evidence from computer simulations to support the accuracy of the approximation. PMID- 17354827 TI - Bronchoscope tracking based on image registration using multiple initial starting points estimated by motion prediction. AB - This paper presents a method for tracking a bronchoscope based on motion prediction and image registration from multiple initial starting points as a function of a bronchoscope navigation system. We try to improve performance of bronchoscope tracking based on image registration using multiple initial guesses estimated using motion prediction. This method basically tracks a bronchoscopic camera by image registration between real bronchoscopic images and virtual ones derived from CT images taken prior to the bronchoscopic examinations. As an initial guess for image registration, we use multiple starting points to avoid falling into local minima. These initial guesses are computed using the motion prediction results obtained from the Kalman filter's output. We applied the proposed method to nine pairs of X-ray CT images and real bronchoscopic video images. The experimental results showed significant performance in continuous tracking without using any positional sensors. PMID- 17354828 TI - 2D/3D registration for measurement of implant alignment after total hip replacement. AB - Measurements of cup alignment after total hip replacement (THR) surgery are typically performed on postoperative pelvic radiographs. Radiographic measurement of cup orientation depends on the position and orientation of the pelvis on the X ray table, and its variability could introduce significant measurement errors. We have developed a tool to accurately measure 3D implant orientation from postoperative antero-posterior radiographs by registering to preoperative CT scans. The purpose of this study is to experimentally and clinically validate the automatic CT/X-ray matching algorithm by comparing the X-ray based measurements of cup orientation with direct 3D measurements from postoperative CT scans. The mean measurement errors (+/- stdev) found in this study were 0.4 degrees +/-0.8 degrees for abduction and 0.6 degrees +/- 0.8 degrees for version. In addition, radiographic pelvic orientation measurements demonstrated a wide range of inter subject variability, with pelvic flexion ranging from -5.9 degrees to 11.2 degrees. PMID- 17354829 TI - 3D/2D model-to-image registration applied to TIPS surgery. AB - We have developed a novel model-to-image registration technique which aligns a 3 dimensional model of vasculature with two semiorthogonal fluoroscopic projections. Our vascular registration method is used to intra-operatively initialize the alignment of a catheter and a preoperative vascular model in the context of image-guided TIPS (Transjugular, Intrahepatic, Portosystemic Shunt formation) surgery. Registration optimization is driven by the intensity information from the projection pairs at sample points along the centerlines of the model. Our algorithm shows speed, accuracy and consistency given clinical data. PMID- 17354830 TI - Ray-tracing based registration for HRCT images of the lungs. AB - Image registration is a fundamental problem in medical imaging. It is especially challenging in lung images compared, for example, with the brain. The challenges include large anatomical variations of human lung and a lack of fixed landmarks inside the lung. This paper presents a new method for lung HRCT image registration. It employs a landmark-based global transformation and a novel ray tracing-based lung surface registration. The proposed surface registration method has two desirable properties: 1) it is fully reversible, and 2) it ensures that the registered lung will be inside the target lung. We evaluated the registration performance by applying it to lung regions mapping. Tested on 46 scans, the registered regions were 89% accurate compared with the ground-truth. PMID- 17354831 TI - Physics-based elastic image registration using splines and including landmark localization uncertainties. AB - We introduce an elastic registration approach which is based on a physical deformation model and uses Gaussian elastic body splines (GEBS). We formulate an extended energy functional related to the Navier equation under Gaussian forces which also includes landmark localization uncertainties. These uncertainties are characterized by weight matrices representing anisotropic errors. Since the approach is based on a physical deformation model, cross-effects in elastic deformations can be taken into account. Moreover, we have a free parameter to control the locality of the transformation for improved registration of local geometric image differences. We demonstrate the applicability of our scheme based on 3D CT images from the Truth Cube experiment, 2D MR images of the brain, as well as 2D gel electrophoresis images. It turns out that the new scheme achieves more accurate results compared to previous approaches. PMID- 17354832 TI - Piecewise-quadrilateral registration by optical flow--applications in contrast enhanced MR imaging of the breast. AB - In this paper we propose a method for the nonrigid registration of contrast enhanced dynamic sequences of magnetic resonance(MR) images. The algorithm has been developed with accuracy in mind, but also has a clinically viable execution time (i.e. a few minutes) as a goal. The algorithm is driven by multiresolution optical flow with the brightness consistency assumption relaxed, subject to a regularized best-fit within a family of transforms. The particular family of transforms we have employed uses a grid of control points and trilinear interpolation. We present validation results from a study simulating non-rigid deformation by a biomechanical model of the breast, with simulated uptake of a contrast agent. We further present results from applying the algorithm as part of a routine breast cancer screening protocol. PMID- 17354833 TI - Iconic feature registration with sparse wavelet coefficients. AB - With the growing acceptance of nonrigid registration as a useful tool to perform clinical research, and in particular group studies, the storage space needed to hold the resulting transforms is deemed to become a concern for vector field based approaches, on top of the traditional computation time issue. In a recent study we lead, which involved the registration of more than 22,000 pairs of T1 MR volumes, this constrain appeared critical indeed. In this paper, we propose to decompose the vector field on a wavelet basis, and let the registration algorithm minimize the number of non-zero coefficients by introducing an L1 penalty. This enables a sparse representation of the vector field which, unlike parametric representations, does not confine the estimated transform into a small parametric space with a fixed uniform smoothness : nonzero wavelet coefficients are optimally distributed depending on the data. Furthermore, we show that the iconic feature registration framework allows to embed the non-differentiable L1 penalty into a C1 energy that can be efficiently minimized by standard optimization techniques. PMID- 17354834 TI - Diffeomorphic registration using B-splines. AB - In this paper we propose a diffeomorphic non-rigid registration algorithm based on free-form deformations (FFDs) which are modelled by B-splines. In contrast to existing non-rigid registration methods based on FFDs the proposed diffeomorphic non-rigid registration algorithm based on free-form deformations (FFDs) which are modelled by B-splines. To construct a diffeomorphic transformation we compose a sequence of free-form deformations while ensuring that individual FFDs are one-to one transformations. We have evaluated the algorithm on 20 normal brain MR images which have been manually segmented into 67 anatomical structures. Using the agreement between manual segmentation and segmentation propagation as a measure of registration quality we have compared the algorithm to an existing FFD registration algorithm and a modified FFD registration algorithm which penalises non-diffeomorphic transformations. The results show that the proposed algorithm generates diffeomorphic transformations while providing similar levels of performance as the existing FFD registration algorithm in terms of registration accuracy. PMID- 17354835 TI - Automatic point landmark matching for regularizing nonlinear intensity registration: application to thoracic CT images. AB - Nonlinear image registration is a prerequisite for a variety of medical image analysis tasks. A frequently used registration method is based on manually or automatically derived point landmarks leading to a sparse displacement field which is densified in a thin-plate spline (TPS) framework. A large problem of TPS interpolation/approximation is the requirement for evenly distributed landmark correspondences over the data set which can rarely be guaranteed by landmark matching algorithms. We propose to overcome this problem by combining the sparse correspondences with intensity-based registration in a generic nonlinear registration scheme based on the calculus of variations. Missing landmark information is compensated by a stronger intensity term, thus combining the strengths of both approaches. An explicit formulation of the generic framework is derived that constrains an intra-modality intensity data term with a regularization term from the corresponding landmarks and an anisotropic image driven displacement regularization term. An evaluation of this algorithm is performed comparing it to an intensity- and a landmark-based method. Results on four synthetically deformed and four clinical thorax CT data sets at different breathing states are shown. PMID- 17354836 TI - Biomechanically based elastic breast registration using mass tensor simulation. AB - We present a new approach for the registration of breast MR images, which are acquired at different time points for observation of lesion evolution. In this registration problem, it is of utmost importance to correct only for differences in patient positioning and to preserve other diagnostically important differences between both images, resulting from anatomical and pathological changes between both acquisitions. Classical free form deformation algorithms are therefore less suited, since they allow too large local volume changes and their deformation is not biomechanically based. Instead of adding constraints or penalties to these methods in order to restrict unwanted deformations, we developed a truly biomechanically based registration method where the position of skin and muscle surface are used as the only boundary conditions. Results of our registration method show an important improvement in correspondence between the reference and the deformed floating image, without introducing physically implausible deformations and within a short computational time. PMID- 17354837 TI - Intensity gradient based registration and fusion of multi-modal images. AB - A particular problem in image registration arises for multimodal images taken from different imaging devices and/or modalities. Starting in 1995, mutual information has shown to be a very successful distance measure for multi-modal image registration. However, mutual information has also a number of well-known drawbacks. Its main disadvantage is that it is known to be highly non-convex and has typically many local maxima. This observation motivate us to seek a different image similarity measure which is better suited for optimization but as well capable to handle multi-modal images. In this work we investigate an alternative distance measure which is based on normalized gradients and compare its performance to Mutual Information. We call the new distance measure Normalized Gradient Fields (NGF). PMID- 17354838 TI - A novel approach for image alignment using a Markov-Gibbs appearance model. AB - A new approach to align an image of a medical object with a given prototype is proposed. Visual appearance of the images, after equalizing their signals, is modelled with a new Markov-Gibbs random field with pairwise interaction model. Similarity to the prototype is measured by a Gibbs energy of signal co occurrences in a characteristic subset of pixel pairs derived automatically from the prototype. An object is aligned by an affine transformation maximizing the similarity by using an automatic initialization followed by gradient search. Experiments confirm that our approach aligns complex objects better than popular conventional algorithms. PMID- 17354839 TI - Evaluation on similarity measures of a surface-to-image registration technique for ultrasound images. AB - Ultrasound is a universal guidance tool for many medical procedures, whereas it is of poor image quality and resolution. Merging high-contrast image information from other image modalities enhances the guidance capability of ultrasound. However, few registration methods work well for it. In this paper we present a surface-to-image registration technique for mono- or multimodal medical data concerning ultrasound. This approach is able to automatically register the object surface to its counterpart in image volume. Three similarity measurements are investigated in the rigid registration experiments of the pubic arch in transrectal ultrasound images. It shown that the selection of the similarity function is related to the ultrasound characteristics of the object to be registered. PMID- 17354840 TI - Backward-warping ultrasound reconstruction for improving diagnostic value and registration. AB - Freehand 3D ultrasound systems acquire sets of B-Mode ultrasound images tagged with position information obtained by a tracking device. For both further processing and clinical use of these ultrasound slice images scattered in space, it is often required to reconstruct them into 3D-rectilinear grid arrays. We propose new efficient methods for this so-called ultrasound spatial compounding using a backward-warping paradigm. They allow to establish 3D-volumes from any scattered freehand ultrasound data with superior quality / speed properties with respect to existing methods. In addition, arbitrary MPR slices can be reconstructed directly from the freehand ultrasound slice set, without the need of an extra volumetric reconstruction step. We qualitatively assess the reconstruction quality and quantitatively compare our compounding method to other algorithms using ultrasound data of the neck and liver. The usefulness of direct MPR reconstruction for multimodal image registration is demonstrated as well. PMID- 17354841 TI - Integrated four dimensional registration and segmentation of dynamic renal MR images. AB - In this paper a novel approach for the registration and segmentation of dynamic contrast enhanced renal MR images is presented. This integrated method is motivated by the observation of the reciprocity between registration and segmentation in 4D time-series images. Fully automated Fourier-based registration with sub-voxel accuracy and semi-automated time-series segmentation were intertwined to improve the accuracy in a multi-step fashion. We have tested our algorithm on several real patient data sets. Clinical validation showed remarkable and consistent agreement between the proposed method and manual segmentation by experts. PMID- 17354842 TI - Fast and robust clinical triple-region image segmentation using one level set function. AB - This paper proposes a novel method for clinical triple-region image segmentation using a single level set function. Triple-region image segmentation finds wide application in the computer aided X-ray, CT, MRI and ultrasound image analysis and diagnosis. Usually multiple level set functions are used consecutively or simultaneously to segment triple-region medical images. These approaches are either time consuming or suffer from the convergence problems. With the new proposed triple-regions level set energy modelling, the triple-region segmentation is handled within the two region level set framework where only one single level set function needed. Since only a single level set function is used, the segmentation is much faster and more robust than using multiple level set functions. Adapted to the clinical setting, individual principal component analysis and a support vector machine classifier based clinical acceleration scheme are used to accelerate the segmentation. The clinical acceleration scheme takes the strengths of both machine learning and the level set method while limiting their weaknesses to achieve automatic and fast clinical segmentation. Both synthesized and practical images are used to test the proposed method. These results show that the proposed method is able to successfully segment the triple region using a single level set function. Also this segmentation is very robust to the placement of initial contour. While still quickly converging to the final image, with the clinical acceleration scheme, our proposed method can be used during pre-processing for automatic computer aided diagnosis and surgery. PMID- 17354843 TI - Fast and robust semi-automatic liver segmentation with haptic interaction. AB - We present a method for semi-automatic segmentation of the liver from CT scans. True 3D interaction with haptic feedback is used to facilitate initialization, i.e., seeding of a fast marching algorithm. Four users initialized 52 datasets and the mean interaction time was 40 seconds. The segmentation accuracy was verified by a radiologist. Volume measurements and segmentation precision show that the method has a high reproducibility. PMID- 17354844 TI - Objective PET lesion segmentation using a spherical mean shift algorithm. AB - PET imagery is a valuable oncology tool for characterizing lesions and assessing lesion response to therapy. These assessments require accurate delineation of the lesion. This is a challenging task for clinicians due to small tumor sizes, blurred boundaries from the large point-spread-function and respiratory motion, inhomogeneous uptake, and nearby high uptake regions. These aspects have led to great variability in lesion assessment amongst clinicians. In this paper, we describe a segmentation algorithm for PET lesions which yields objective segmentations without operator variability. The technique is based on the mean shift algorithm, applied in a spherical coordinate frame to yield a directional assessment of foreground and background and a varying background model. We analyze the algorithm using clinically relevant hybrid digital phantoms and illustrate its effectiveness relative to other techniques. PMID- 17354845 TI - Multilevel segmentation and integrated bayesian model classification with an application to brain tumor segmentation. AB - We present a new method for automatic segmentation of heterogeneous image data, which is very common in medical image analysis. The main contribution of the paper is a mathematical formulation for incorporating soft model assignments into the calculation of affinities, which are traditionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm. We apply the technique to the task of detecting and segmenting brain tumor and edema in multimodal MR volumes. Our results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of brain tumor. PMID- 17354846 TI - A new adaptive probabilistic model of blood vessels for segmenting MRA images. AB - A new physically justified adaptive probabilistic model of blood vessels on magnetic resonance angiography (MRA) images is proposed. The model accounts for both laminar (for normal subjects) and turbulent blood flow (in abnormal cases like anemia or stenosis) and results in a fast algorithm for extracting a 3D cerebrovascular system from the MRA data. Experiments with synthetic and 50 real data sets confirm the high accuracy of the proposed approach. PMID- 17354847 TI - Segmentation of thalamic nuclei from DTI using spectral clustering. AB - Recent work shows that diffusion tensor imaging (DTI) can help resolving thalamic nuclei based on the characteristic fiber orientation of the corticothalamic/thalamocortical striations within each nucleus. In this paper we describe a novel segmentation method based on spectral clustering. We use Markovian relaxation to handle spatial information in a natural way, and we explicitly minimize the normalized cut criteria of the spectral clustering for a better optimization. Using this modified spectral clustering algorithm, we can resolve the organization of the thalamic nuclei into groups and subgroups solely based on the voxel affinity matrix, avoiding the need for explicitly defined cluster centers. The identification of nuclear subdivisions can facilitate localization of functional activation and pathology to individual nuclear subgroups. PMID- 17354848 TI - Multiclassifier fusion in human brain MR segmentation: modelling convergence. AB - Segmentations of MR images of the human brain can be generated by propagating an existing atlas label volume to the target image. By fusing multiple propagated label volumes, the segmentation can be improved. We developed a model that predicts the improvement of labelling accuracy and precision based on the number of segmentations used as input. Using a cross-validation study on brain image data as well as numerical simulations, we verified the model. Fit parameters of this model are potential indicators of the quality of a given label propagation method or the consistency of the input segmentations used. PMID- 17354849 TI - Active surface approach for extraction of the human cerebral cortex from MRI. AB - Segmentation of the human cerebral cortex from MRI has been subject of much attention during the last decade. Methods based on active surfaces for representing and extracting the cortical boundaries have shown promising results. We present an active surface method, that extracts the inner and outer cortical boundaries using a combination of different vector fields and a local weighting method based on the intrinsic properties of the deforming surface. Our active surface model deforms polygonal meshes to fit the boundaries of the cerebral cortex using a force balancing scheme. As a result of the local weighting strategy and a self-intersection constraint, the method is capable of modelling tight sulci where the image edge is missing or obscured. The performance of the method is evaluated using both real and simulated MRI data. PMID- 17354850 TI - Integrated graph cuts for brain MRI segmentation. AB - Brain MRI segmentation remains a challenging problem in spite of numerous existing techniques. To overcome the inherent difficulties associated with this segmentation problem, we present a new method of information integration in a graph based framework. In addition to image intensity, tissue priors and local boundary information are integrated into the edge weight metrics in the graph. Furthermore, inhomogeneity correction is incorporated by adaptively adjusting the edge weights according to the intermediate inhomogeneity estimation. In the validation experiments of simulated brain MRIs, the proposed method outperformed a segmentation method based on iterated conditional modes (ICM), which is a commonly used optimization method in medical image segmentation. In the experiments of real neonatal brain MRIs, the results of the proposed method have good overlap with the manual segmentations by human experts. PMID- 17354852 TI - A general framework for image segmentation using ordered spatial dependency. AB - The segmentation problem appears in most medical imaging applications. Many research groups are pushing toward a whole body segmentation based on atlases. With a similar objective, we propose a general framework to segment several structures. Rather than inventing yet another segmentation algorithm, we introduce inter-structure spatial dependencies to work with existing segmentation algorithms. Ranking the structures according to their dependencies, we end up with a hierarchical approach that improves each individual segmentation and provides automatic initializations. The best ordering of the structures can be learned off-line. We apply this framework to the segmentation of several structures in brain MR images. PMID- 17354851 TI - Validation of image segmentation by estimating rater bias and variance. AB - The accuracy and precision of segmentations of medical images has been difficult to quantify in the absence of a "ground truth" or reference standard segmentation for clinical data. Although physical or digital phantoms can help by providing a reference standard, they do not allow the reproduction of the full range of imaging and anatomical characteristics observed in clinical data. An alternative assessment approach is to compare to segmentations generated by domain experts. Segmentations may be generated by raters who are trained experts or by automated image analysis algorithms. Typically these segmentations differ due to intra rater and inter-rater variability. The most appropriate way to compare such segmentations has been unclear. We present here a new algorithm to enable the estimation of performance characteristics, and a true labeling, from observations of segmentations of imaging data where segmentation labels may be ordered or continuous measures. This approach may be used with, amongst others, surface, distance transform or level set representations of segmentations, and can be used to assess whether or not a rater consistently over-estimates or under-estimates the position of a boundary. PMID- 17354853 TI - Constructing a probabilistic model for automated liver region segmentation using non-contrast X-ray torso CT images. AB - A probabilistic model was proposed in this research for fully-automated segmentation of liver region in non-contrast X-ray torso CT images. This probabilistic model was composed of two kinds of probability that show the location and density (CT number) of the liver in CT images. The probability of the liver on the spatial location was constructed from a number of CT scans in which the liver regions were pre-segmented manually as gold standards. The probability of the liver on density was estimated specifically using a Gaussian function. The proposed probabilistic model was used for automated liver segmentation from non-contrast CT images. 132 cases of the CT scans were used for the probabilistic model construction and then this model was applied to segment liver region based on a leave-one-out method. The performances of the probabilistic model were evaluated by comparing the segmented liver with the gold standard in each CT case. The validity and usefulness of the proposed model were proved. PMID- 17354854 TI - Modeling of intensity priors for knowledge-based level set algorithm in calvarial tumors segmentation. AB - In this paper, an automatic knowledge-based framework for level set segmentation of 3D calvarial tumors from Computed Tomography images is presented. Calvarial tumors can be located in both soft and bone tissue, occupying wide range of image intensities, making automatic segmentation and computational modeling a challenging task. The objective of this study is to analyze and validate different approaches in intensity priors modeling with an attention to multiclass problems. One, two, and three class Gaussian mixture models and a discrete model are evaluated considering probability density modeling accuracy and segmentation outcome. Segmentation results were validated in comparison to manually segmented golden standards, using analysis in ROC (Receiver Operating Curve) space and Dice similarity coefficient. PMID- 17354855 TI - A comparison of breast tissue classification techniques. AB - It is widely accepted in the medical community that breast tissue density is an important risk factor for the development of breast cancer. Thus, the development of reliable automatic methods for classification of breast tissue is justified and necessary. Although different approaches in this area have been proposed in recent years, only a few are based on the BIRADS classification standard. In this paper we review different strategies for extracting features in tissue classification systems, and demonstrate, not only the feasibility of estimating breast density using automatic computer vision techniques, but also the benefits of segmentation of the breast based on internal tissue information. The evaluation of the methods is based on the full MIAS database classified according to BIRADS categories, and agreement between automatic and manual classification of 82% was obtained. PMID- 17354856 TI - Analysis of skeletal microstructure with clinical multislice CT. AB - In view of the great effects of osteoporosis on public health, it would be of great value to be able to measure the three-dimensional structure of trabecular bone in vivo as a means to diagnose and quantify the disease. The aim of this work was to implement a method for quantitative characterisation of trabecular bone structure using clinical CT. Several previously described parameters have been calculated from volumes acquired with a 64-slice clinical scanner. Using automated region growing, distance transforms and three-dimensional thinning, measures describing the number, thickness and spacing of bone trabeculae was obtained. Fifteen bone biopsies were analysed. The results were evaluated using micro-CT as reference. For most parameters studied, the absolute values did not agree well with the reference method, but several parameters were closely correlated with the reference method. The shortcomings appear to be due to the low resolution and high noise level. However, the high correlation found between clinical CT and micro-CT measurements suggest that it might be possible to monitor changes in the trabecular structure in vivo. PMID- 17354857 TI - An energy minimization approach to the data driven editing of presegmented images/volumes. AB - Fully automatic, completely reliable segmentation in medical images is an unrealistic expectation with today's technology. However, many automatic segmentation algorithms may achieve a near-correct solution, incorrect only in a small region. For these situations, an interactive editing tool is required, ideally in 3D, that is usually left to a manual correction. We formulate the editing task as an energy minimization problem that may be solved with a modified version of either graph cuts or the random walker 3D segmentation algorithms. Both algorithms employ a seeded user interface, that may be used in this scenario for a user to seed erroneous voxels as belonging to the foreground or the background. In our formulation, it is unnecessary for the user to specify both foreground and background seeds. PMID- 17354858 TI - Accurate banded graph cut segmentation of thin structures using laplacian pyramids. AB - The Graph Cuts method of interactive segmentation has become very popular in recent years. This method performs at interactive speeds for smaller images/volumes, but an unacceptable amount of storage and computation time is required for the large images/volumes common in medical applications. The Banded Graph Cut (BGC) algorithm was proposed to drastically increase the computational speed of Graph Cuts, but is limited to the segmentation of large, roundish objects. In this paper, we propose a modification of BGC that uses the information from a Laplacian pyramid to include thin structures into the band. Therefore, we retain the computational efficiency of BGC while providing quality segmentations on thin structures. We make quantitative and qualitative comparisons with BGC on images containing thin objects. Additionally, we show that the new parameter introduced in our modification provides a smooth transition from BGC to traditional Graph Guts. PMID- 17354859 TI - Segmentation of neck lymph nodes in CT datasets with stable 3D mass-spring models. AB - The quantitative assessment of neck lymph nodes in the context of malign tumors requires an efficient segmentation technique for lymph nodes in tomographic 3D datasets. We present a Stable 3D Mass-Spring Model for lymph node segmentation in CT datasets. Our model for the first time represents concurrently the characteristic gray value range, directed contour information as well as shape knowledge, which leads to a much more robust and efficient segmentation process. Our model design and segmentation accuracy are both evaluated with lymph nodes from clinical CT neck datasets. PMID- 17354860 TI - Supervised probabilistic segmentation of pulmonary nodules in CT scans. AB - An automatic method for lung nodule segmentation from computed tomography (CT) data is presented that is different from previous work in several respects. Firstly, it is supervised; it learns how to obtain a reliable segmentation from examples in a training phase. Secondly, the method provides a soft, or probabilistic segmentation, thus taking into account the uncertainty inherent in this segmentation task. The method is trained and tested on a public data set of 23 nodules for which soft labelings are available. The new method is shown to outperform a previously published conventional method. By merely changing the training data, non-solid nodules can also be segmented. PMID- 17354861 TI - MR image segmentation using phase information and a novel multiscale scheme. AB - This paper considers the problem of automatic classification of textured tissues in 3D MRI. More specifically, it aims at validating the use of features extracted from the phase of the MR signal to improve texture discrimination in bone segmentation. This extra information provides better segmentation, compared to using magnitude only features. We also present a novel multiscale scheme to improve the speed of pixel based classification algorithm, such as support vector machines. This algorithm dramatically increases the speed of the segmentation process by an order of magnitude through a reduction of the number of pixels that needs to be classified in the image. PMID- 17354862 TI - Multi-resolution vessel segmentation using normalized cuts in retinal images. AB - Retinal vessel segmentation is an essential step of the diagnoses of various eye diseases. In this paper, we propose an automatic, efficient and unsupervised method based on gradient matrix, the normalized cut criterion and tracking strategy. Making use of the gradient matrix of the Lucas-Kanade equation, which consists of only the first order derivatives, the proposed method can detect a candidate window where a vessel possibly exists. The normalized cut criterion, which measures both the similarity within groups and the dissimilarity between groups, is used to search a local intensity threshold to segment the vessel in a candidate window. The tracking strategy makes it possible to extract thin vessels without being corrupted by noise. Using a multi-resolution segmentation scheme, vessels with different widths can be segmented at different resolutions, although the window size is fixed. Our method is tested on a public database. It is demonstrated to be efficient and insensitive to initial parameters. PMID- 17354863 TI - Simulation of local and global atrophy in Alzheimer's disease studies. AB - We propose a method for atrophy simulation in structural MR images based on finite-element methods, providing data for objective evaluation of atrophy measurement techniques. The modelling of diffuse global and regional atrophy is based on volumetric measurements from patients with known disease and guided by clinical knowledge of the relative pathological involvement of regions. The consequent biomechanical readjustment of structures is modelled using conventional physics-based techniques based on tissue properties and simulating plausible deformations with finite-element methods. Tissue characterization is performed by means of the meshing of a labelled brain atlas, creating a reference volumetric mesh, and a partial volume tissue model is used to reduce the impact of the mesh discretization. An example of simulated data is shown and a visual evaluation protocol used by experts has been developed to assess the degree of realism of the simulated images. First results demonstrate the potential of the proposed methodology. PMID- 17354864 TI - Brain surface conformal parameterization with algebraic functions. AB - In medical imaging, parameterized 3D surface models are of great interest for anatomical modeling and visualization, statistical comparisons of anatomy, and surface-based registration and signal processing. Here we introduce a parameterization method based on algebraic functions. By solving the Yamabe equation with the Ricci flow method, we can conformally map a brain surface to a multi-hole disk. The resulting parameterizations do not have any singularities and are intrinsic and stable. To illustrate the technique, we computed parameterizations of several types of anatomical surfaces in MRI scans of the brain, including the hippocampi and the cerebral cortices with various landmark curves labeled. For the cerebral cortical surfaces, we show the parameterization results are consistent with selected landmark curves and can be matched to each other using constrained harmonic maps. Unlike previous planar conformal parameterization methods, our algorithm does not introduce any singularity points. It also offers a method to explicitly match landmark curves between anatomical surfaces such as the cortex, and to compute conformal invariants for statistical comparisons of anatomy. PMID- 17354865 TI - Logarithm odds maps for shape representation. AB - The concept of the Logarithm of the Odds (LogOdds) is frequently used in areas such as artificial neural networks, economics, and biology. Here, we utilize LogOdds for a shape representation that demonstrates desirable properties for medical imaging. For example, the representation encodes the shape of an anatomical structure as well as the variations within that structure. These variations are embedded in a vector space that relates to a probabilistic model. We apply our representation to a voxel based segmentation algorithm. We do so by embedding the manifold of Signed Distance Maps (SDM) into the linear space of LogOdds. The LogOdds variant is superior to the SDM model in an experiment segmenting 20 subjects into subcortical structures. We also use LogOdds in the non-convex interpolation between space conditioned distributions. We apply this model to a longitudinal schizophrenia study using quadratic splines. The resulting time-continuous simulation of the schizophrenic aging process has a higher accuracy then a model based on convex interpolation. PMID- 17354866 TI - Multi-modal image registration using the generalized survival exponential entropy. AB - This paper introduces a new similarity measure for multimodal image registration task. The measure is based on the generalized survival exponential entropy (GSEE) and mutual information (GSEE-MI). Since GSEE is estimated from the cumulative distribution function instead of the density function, it is observed that the interpolation artifact is reduced. The method has been tested on four real MR-CT data sets. The experimental results show that the GSEE-MI-based method is more robust than the conventional MI-based method. The accuracy is comparable for both methods. PMID- 17354867 TI - Quantitative vertebral morphometry using neighbor-conditional shape models. AB - A novel method for vertebral fracture quantification from X-ray images is presented. Using pairwise conditional shape models trained on a set of healthy spines, the most likely normal vertebra shapes are estimated conditional on all other vertebrae in the image. The differences between the true shape and the reconstructed normal shape is subsequently used as a measure of abnormality. In contrast with the current (semi-)quantitative grading strategies this method takes the full shape into account, it uses a patient-specific reference by combining population-based information on biological variation in vertebra shape and vertebra interrelations, and it provides a continuous measure of deformity. The method is demonstrated on 212 lateral spine radiographs with in total 78 fractures. The distance between prediction and true shape is 1.0 mm for unfractured vertebrae and 3.7 mm for fractures, which makes it possible to diagnose and assess the severity of a fracture. PMID- 17354868 TI - Anatomically constrained deformation for design of cranial implant: methodology and validation. AB - We present a new approach for cranial implant design which uses anatomical constrained deformation based on reference models. The methodological framework contains three steps: patient-specific generation of the reference model containing the anatomical constraints about the skull shape; determination of the spatial correspondence between the patient skull and the reference model by 3D matching; adaptive deformation of the fragment on the reference model corresponding to the defect area on the patient skull for implant design. The proposed method was validated by simulating the reconstruction of artificially generated defects on healthy skulls. The validation results show that this approach can generate implant geometry very fast and with satisfactory quality. This approach also outperforms the surface interpolation method in reconstructing cranial defects. PMID- 17354869 TI - Open-curve shape correspondence without endpoint correspondence. AB - Shape correspondence is the foundation for accurate statistical shape analysis; this is usually accomplished by identifying a set of sparsely sampled and well corresponded landmark points across a population of shape instances. However, most available shape correspondence methods can only effectively deal with complete-shape correspondence, where a one-to-one mapping is assumed between any two shape instances. In this paper, we present a novel algorithm to correspond 2D open-curve partial-shape instances where one shape instance may only be mapped to part of the other, i.e., the endpoints of these open-curve shape instances are not presumably corresponded. In this algorithm, some initially identified landmarks, including the ones at or near the endpoints of the shape instances, are refined by allowing them to slide freely along the shape contour to minimize the shape-correspondence error. To avoid being trapped into local optima, we develop a simple method to construct a better initialization of the landmarks and introduce some additional constraints to the landmark sliding. We evaluate the proposed algorithm on 32 femur shape instances in comparison to some current methods. PMID- 17354870 TI - Reconstruction of patient-specific 3D bone surface from 2D calibrated fluoroscopic images and point distribution model. AB - Reconstruction of patient-specific 3D bone surface from 2D calibrated fluoroscopic images and a point distribution model is discussed. We present a 2D/3D reconstruction scheme combining statistical extrapolation and regularized shape deformation with an iterative image-to-model correspondence establishing algorithm, and show its application to reconstruct the surface of proximal femur. The image-to-model correspondence is established using a non-rigid 2D point matching process, which iteratively uses a symmetric injective nearest-neighbor mapping operator and 2D thin-plate splines based deformation to find a fraction of best matched 2D point pairs between features detected from the fluoroscopic images and those extracted from the 3D model. The obtained 2D point pairs are then used to set up a set of 3D point pairs such that we turn a 2D/3D reconstruction problem to a 3D/3D one. We designed and conducted experiments on 11 cadaveric femurs to validate the present reconstruction scheme. An average mean reconstruction error of 1.2 mm was found when two fluoroscopic images were used for each bone. It decreased to 1.0 mm when three fluoroscopic images were used. PMID- 17354871 TI - A pilot study of robot-assisted cochlear implant surgery using steerable electrode arrays. AB - This paper presents results of a pilot study evaluating the efficacy of robotic assistance using novel steerable electrode arrays for cochlear implant surgery. The current surgical setup of cochlear implant surgery is briefly reviewed and its limitations are highlighted. In an effort to reduce trauma to the structure of the cochlea, the kinematics and path planning for novel cochlear steerable electrodes are developed to minimize the interaction forces between the electrode and the cochlea. An experimental robotic system is used to compare the electrode insertion forces of steerable implants with those of nonsteerable electrodes. The results of these experiments show about 70% reduction in the insertion forces when steerable electrodes are used with our proposed path planning and control. A distance metric explaining this reduction in the insertion force is defined and experimentally validated. Although this is only a preliminary study, we believe that these results provide a strong indication to the potential of robot-assisted cochlear implant surgery to provide a significant reduction in trauma rates during cochlear implant surgery. PMID- 17354872 TI - Robot-assisted prostate brachytherapy. AB - In contemporary brachytherapy procedures, needle placement at the desired target is challenging due to a variety of reasons. A robot-assisted brachytherapy system can improve the needle placement and seed delivery resulting in enhanced patient care. In this paper we present a 16 DOF (degrees-of-freedom) robotic system (9DOF positioning module and 7 DOF surgery module) developed and fabricated for prostate brachytherapy. Techniques to reduce needle deflection and target movement have been incorporated after verifying with extensive experiments. Provisions for needle motion and force feedback have been included into the system for improving the robot control and seed delivery. Preliminary experimental results reveal that the prototype system is quite accurate (sub millimeter) in placing brachytherapy needles. PMID- 17354873 TI - Design and validation of an image-guided robot for small animal research. AB - We developed an image-guided robot system to achieve highly accurate placement of thin needles and probes into in-vivo rodent tumor tissue in a predefined pattern that is specified on a preoperative image. This system can be used for many experimental procedures where the goal is to correlate a set of physical measurements with a corresponding set of image intensities or, more generally, to perform a physical action at a set of anatomic points identified on a preoperative image. This paper focuses on the design and validation of the robot system, where the first application is to insert oxygen measurement probes in a three-dimensional (3D) grid pattern defined with respect to a PET scan of a tumor. The design is compatible with CT and MRI, which we plan to use to identify targets for biopsy and for the injection of adenoviral sequences for gene therapy. The validation is performed using a phantom and includes a new method for estimating the Fiducial Localization Error (FLE) based on the measured Fiducial Distance Error (FDE). PMID- 17354874 TI - GPU based real-time instrument tracking with three dimensional ultrasound. AB - Real-time 3D ultrasound can enable new image-guided surgical procedures, but high data rates prohibit the use of traditional tracking techniques. We present a new method based on the modified Radon transform that identifies the axis of instrument shafts as bright patterns in planar projections. Instrument rotation and tip location are then determined using fiducial markers. These techniques are amenable to rapid execution on the current generation of personal computer graphics processor units (GPU). Our GPU implementation detected a surgical instrument in 31 ms, sufficient for real-time tracking at the 26 volumes per second rate of the ultrasound machine. A water tank experiment found instrument tip position errors of less than 0.2 mm, and an in vivo study tracked an instrument inside a beating porcine heart. The tracking results showed good correspondence to the actual movements of the instrument. PMID- 17354875 TI - Shape-driven 3D segmentation using spherical wavelets. AB - This paper presents a novel active surface segmentation algorithm using a multiscale shape representation and prior. We define a parametric model of a surface using spherical wavelet functions and learn a prior probability distribution over the wavelet coefficients to model shape variations at different scales and spatial locations in a training set. Based on this representation, we derive a parametric active surface evolution using the multiscale prior coefficients as parameters for our optimization procedure to naturally include the prior in the segmentation framework. Additionally, the optimization method can be applied in a coarse-to-fine manner. We apply our algorithm to the segmentation of brain caudate nucleus, of interest in the study of schizophrenia. Our validation shows our algorithm is computationally efficient and outperforms the Active Shape Model algorithm by capturing finer shape details. PMID- 17354876 TI - Artificially enlarged training set in image segmentation. AB - Due to small training sets, statistical shape models constrain often too much the deformation in medical image segmentation. Hence, an artificial enlargement of the training set has been proposed as a solution for the problem. In this paper, the error sources in the statistical shape model based segmentation were analyzed and the optimization processes were improved. The method was evaluated with 3D cardiac MR volume data. The enlargement method based on non-rigid movement produced good results--with 250 artificial modes, the average error for four chamber model was 2.11 mm when evaluated using 25 subjects. PMID- 17354877 TI - Segmenting lung fields in serial chest radiographs using both population and patient-specific shape statistics. AB - This paper presents a new deformable model using both population-based and patient-specific shape statistics to segment lung fields from serial chest radiographs. First, a modified scale-invariant feature transform (SIFT) local descriptor is used to characterize the image features in the vicinity of each pixel, so that the deformable model deforms in a way that seeks for the region with similar SIFT local descriptors. Second, the deformable model is constrained by both population-based and patient-specified shape statistics. Initially, population-based shape statistics takes most of the rules when the number of serial images is small; gradually, patient-specific shape statistics takes more rules after a sufficient number of segmentation results on the same patient have been obtained. The proposed deformable model can adapt to the shape variability of different patients, and obtain more robust and accurate segmentation results. PMID- 17354878 TI - 4D shape priors for a level set segmentation of the left myocardium in SPECT sequences. AB - We develop a 4D (3D plus time) statistical shape model for implicit level set based shape representations. To this end, we represent hand segmented training sequences of the left ventricle by respective 4-dimensional embedding functions and approximate these by a principal component analysis. In contrast to recent 4D models on explicit shape representations, the implicit shape model developed in this work does not require the computation of point correspondences which is known to be quite challenging, especially in higher dimensions. Experimental results on the segmentation of SPECT sequences of the left myocardium confirm that the 4D shape model outperforms respective 3D models, because it takes into account a statistical model of the temporal shape evolution. PMID- 17354879 TI - Cell segmentation using coupled level sets and graph-vertex coloring. AB - Current level-set based approaches for segmenting a large number of objects are computationally expensive since they require a unique level set per object (the N level set paradigm), or [log2N] level sets when using a multiphase interface tracking formulation. Incorporating energy-based coupling constraints to control the topological interactions between level sets further increases the computational cost to O(N2). We propose a new approach, with dramatic computational savings, that requires only four, or fewer, level sets for an arbitrary number of similar objects (like cells) using the Delaunay graph to capture spatial relationships. Even more significantly, the coupling constraints (energy-based and topological) are incorporated using just constant O(1) complexity. The explicit topological coupling constraint, based on predicting contour collisions between adjacent level sets, is developed to further prevent false merging or absorption of neighboring cells, and also reduce fragmentation during level set evolution. The proposed four-color level set algorithm is used to efficiently and accurately segment hundreds of individual epithelial cells within a moving monolayer sheet from time-lapse images of in vitro wound healing without any false merging of cells. PMID- 17354880 TI - 3D histological reconstruction of fiber tracts and direct comparison with diffusion tensor MRI tractography. AB - A classical neural tract tracer, WGA-HRP, was injected at multiple sites within the brain of a macaque monkey. Histological sections of the labeled fiber tracts were reconstructed in 3D, and the fibers were segmented and registered with the anatomical post-mortem MRI from the same animal. Fiber tracing along the same pathways was performed on the DTI data using a classical diffusion tracing technique. The fibers derived from the DTI were compared with those segmented from the histology in order to evaluate the performance of DTI fiber tracing. While there was generally good agreement between the two methods, our results reveal certain limitations of DTI tractography, particularly at regions of fiber tract crossing or bifurcation. PMID- 17354881 TI - Rician noise removal in diffusion tensor MRI. AB - Rician noise introduces a bias into MRI measurements that can have a significant impact on the shapes and orientations of tensors in diffusion tensor magnetic resonance images. This is less of a problem in structural MRI, because this bias is signal dependent and it does not seriously impair tissue identification or clinical diagnoses. However, diffusion imaging is used extensively for quantitative evaluations, and the tensors used in those evaluations are biased in ways that depend on orientation and signal levels. This paper presents a strategy for filtering diffusion tensor magnetic resonance images that addresses these issues. The method is a maximum a posteriori estimation technique that operates directly on the diffusion weighted images and accounts for the biases introduced by Rician noise. We account for Rician noise through a data likelihood term that is combined with a spatial smoothing prior. The method compares favorably with several other approaches from the literature, including methods that filter diffusion weighted imagery and those that operate directly on the diffusion tensors. PMID- 17354882 TI - Anisotropy creases delineate white matter structure in diffusion tensor MRI. AB - Current methods for extracting models of white matter architecture from diffusion tensor MRI are generally based on fiber tractography. For some purposes a compelling alternative may be found in analyzing the first and second derivatives of diffusion anisotropy. Anisotropy creases are ridges and valleys of locally extremal anisotropy, where the gradient of anisotropy is orthogonal to one or more eigenvectors of its Hessian. We propose that anisotropy creases provide a basis for extracting a skeleton of white matter pathways, in that ridges of anisotropy coincide with interiors of fiber tracts, and valleys of anisotropy coincide with the interfaces between adjacent but distinctly oriented tracts. We describe a crease extraction algorithm that generates high-quality polygonal models of crease surfaces, then demonstrate the method on a measured diffusion tensor dataset, and visualize the result in combination with tractography to confirm its anatomic relevance. PMID- 17354883 TI - Evaluation of 3-D shape reconstruction of retinal fundus. AB - We present a method for the 3-D shape reconstruction of the retinal fundus from stereo paired images. Detection of retinal elevation plays a critical role in the diagnosis and management of many retinal diseases. However, since the shape of ocular fundus is nearly planar, its 3-D depth range is very narrow. Therefore, we use the location of vascular bifurcations and a plane+parallax approach to provide a robust estimation of the epipolar geometry. Matching is then performed using a mutual information algorithm for accurate estimation of the disparity maps. To validate our results, in the absence of camera calibration, we compared the results with measurements from the current clinical gold standard, optical coherence tomography (OCT). PMID- 17354884 TI - Comparing the similarity of statistical shape models using the Bhattacharya metric. AB - A variety of different methods of finding correspondences across sets of images to build statistical shape models have been proposed, each of which is likely to result in a different model. When dealing with large datasets (particularly in 3D), it is difficult to evaluate the quality of the resulting models. However, if the different methods are successfully modelling the true underlying shape variation, the resulting models should be similar. If two different techniques lead to similar models, it suggests that they are indeed approximating the true shape change. In this paper we explore a method of comparing statistical shape models by evaluating the Bhattacharya overlap between their implied shape distributions. We apply the technique to investigate the similarity of three models of the same 3D dataset constructed using different methods. PMID- 17354885 TI - Improving segmentation of the left ventricle using a two-component statistical model. AB - Quality of segmentations obtained by 3D Active Appearance Models (AAMs) crucially depends on underlying training data. MRI heart data, however, often come noisy, incomplete, with respiratory-induced motion, and do not fulfill necessary requirements for building an AAM. Moreover, AAMs are known to fail when attempting to model local variations. Inspired by the recent work on split models we propose an alternative to the methods based on pure 3D AAM segmentation. We interconnect a set of 2D AAMs by a 3D shape model. We show that our approach is able to cope with imperfect data and improves segmentations by 11% on average compared to 3D AAMs. PMID- 17354886 TI - An approach for the automatic cephalometric landmark detection using mathematical morphology and active appearance models. AB - Cephalometric analysis of lateral radiographs of the head is an important diagnosis tool in orthodontics. Based on manually locating specific landmarks, it is a tedious, time-consuming and error prone task. In this paper, we propose an automated system based on the use of Active Appearance Models (AAMs). Special attention has been paid to clinical validation of our method since previous work in this field used few images, was tested in the training set and/or did not take into account the variability of the images. In this research, a top-hat transformation was used to correct the intensity inhomogeneity of the radiographs generating a consistent training set that overcomes the above described drawbacks. The AAM was trained using 96 hand-annotated images and tested with a leave-one-out scheme obtaining an average accuracy of 2.48mm. Results show that AAM combined with mathematical morphology is the suitable method for clinical cephalometric applications. PMID- 17354887 TI - Automatic segmentation of jaw tissues in CT using active appearance models and semi-automatic landmarking. AB - Preoperative planning systems are commonly used for oral implant surgery. One of the objectives is to determine if the quantity and quality of bone is sufficient to sustain an implant while avoiding critical anatomic structures. We aim to automate the segmentation of jaw tissues on CT images: cortical bone, trabecular core and especially the mandibular canal containing the dental nerve. This nerve must be avoided during implant surgery to prevent lip numbness. Previous work in this field used thresholds or filters and needed manual initialization. An automated system based on the use of Active Appearance Models (AAMs) is proposed. Our contribution is a completely automated segmentation of tissues and a semi automatic landmarking process necessary to create the AAM model. The AAM is trained using 215 images and tested with a leave-4-out scheme. Results obtained show an initialization error of 3.25% and a mean error of 1.63mm for the cortical bone, 2.90 mm for the trabecular core, 4.76 mm for the mandibular canal and 3.40 mm for the dental nerve. PMID- 17354888 TI - Morphometric analysis for pathological abnormality detection in the skull vaults of adolescent idiopathic scoliosis girls. AB - In this paper, we present a comprehensive framework to detect morphological changes in skull vaults of adolescent idiopathic scoliosis girls. To our knowledge, this is the first attempt to use a combination of medical knowledge, image analysis techniques, statistical learning tools, and scientific visualization methods to detect skull morphological changes. The shape analysis starts from a reliable 3-D segmentation of the skull using thresholding and math morphological operations. The gradient vector flow is used to model the skull vault surface, which is followed by a spherically uniform sampling. The scale normalized distances from the shape centroid to sample points are defined as the features. The most discriminative features are selected using recursive feature elimination for support vector machine. The results of this study specify the skull vault surface changes and shed light on building the evidence of bone formation abnormality in AIS girls. PMID- 17354889 TI - A novel quantitative validation of the cortical surface reconstruction algorithm using MRI phantom: issues on local geometric accuracy and cortical thickness. AB - Cortical surface reconstruction is important for functional brain mapping and morphometric analysis of the brain cortex. Several methods have been developed for the faithful reconstruction of surface models which describe the true cortical surface in both geometry and topology. However there has been no explicit method for the quantitative evaluation of the whole-cortical-surface models. In this study, we present a novel phantom-based evaluation method of the cortical surface reconstruction algorithm and quantitatively validated the local morphometric accuracy of CLASP which is one of the well-established reconstruction methods. The evaluation included local geometrical accuracy and performance of cortical thickness measure. The validation study revealed that there were some underestimations of cortical thickness measure using CLASP in the ventral and sulcal areas of the cortex and overestimations in the gyral areas and inferior temporal lobe. This study could present a generic metric for the quantitative evaluation of cortical surface reconstruction algorithm. PMID- 17354890 TI - Multivariate statistics of the Jacobian matrices in tensor based morphometry and their application to HIV/AIDS. AB - Tensor-based morphometry (TBM) is widely used in computational anatomy as a means to understand shape variation between structural brain images. A 3D nonlinear registration technique is typically used to align all brain images to a common neuroanatomical template, and the deformation fields are analyzed statistically to identify group differences in anatomy. However, the differences are usually computed solely from the determinants of the Jacobian matrices that are associated with the deformation fields computed by the registration procedure. Thus, much of the information contained within those matrices gets thrown out in the process. Only the magnitude of the expansions or contractions is examined, while the anisotropy and directional components of the changes are ignored. Here we remedy this problem by computing multivariate shape change statistics using the strain matrices. As the latter do not form a vector space, means and covariances are computed on the manifold of positive-definite matrices to which they belong. We study the brain morphology of 26 HIV/AIDS patients and 14 matched healthy control subjects using our method. The images are registered using a high dimensional 3D fluid registration algorithm, which optimizes the Jensen-Renyi divergence, an information-theoretic measure of image correspondence. The anisotropy of the deformation is then computed. We apply a manifold version of Hotelling's T2 test to the strain matrices. Our results complement those found from the determinants of the Jacobians alone and provide greater power in detecting group differences in brain structure. PMID- 17354891 TI - Highly accurate segmentation of brain tissue and subcortical gray matter from newborn MRI. AB - The segmentation of newborn brain MRI is important for assessing and directing treatment options for premature infants at risk for developmental disorders, abnormalities, or even death. Segmentation of infant brain MRI is particularly challenging when compared with the segmentation of images acquired from older children and adults. We sought to develop a fully automated segmentation strategy and present here a Bayesian approach utilizing an atlas of priors derived from previous segmentations and a new scheme for automatically selecting and iteratively refining classifier training data using the STAPLE algorithm. Results have been validated by comparison to hand-drawn segmentations. PMID- 17354892 TI - Transformation model and constraints cause bias in statistics on deformation fields. AB - This work investigates the effects of nonrigid transformation model and deformation constraints on the results of deformation-based morphometry (DBM) studies. We evaluate three popular registration algorithms: a B-spline algorithm with several different constraint terms, Thirion's demons algorithm, and a curvature PDE-based algorithm. All algorithms produced virtually identical overlaps of corresponding structures, but the underlying deformation fields were very different, and the Jacobian determinant values within homogeneous structures varied dramatically. In several cases, we observed bi-modal distributions of Jacobians within a region that violate the assumption of gaussianity that underlies many statistical tests. Our results demonstrate that, even with perfect overlap of corresponding structures, the statistics of Jacobian values are affected by bias due to design elements of the particular nonrigid registration. These findings are not limited to DBM, but also apply to voxel-based morphometry to the extent that it includes a Jacobian-based correction step ("modulation"). PMID- 17354893 TI - Limits on estimating the width of thin tubular structures in 3D images. AB - This work studies limits on estimating the width of thin tubular structures in 3D images. Based on nonlinear estimation theory we analyze the minimal stochastic error of estimating the width. Given a 3D analytic model of the image intensities of tubular structures, we derive a closed-form expression for the Cramer-Rao bound of the width estimate under image noise. We use the derived lower bound as a benchmark and compare it with three previously proposed accuracy limits for vessel width estimation. Moreover, by experimental investigations we demonstrate that the derived lower bound can be achieved by fitting a 3D parametric intensity model directly to the image data. PMID- 17354894 TI - Toward interactive user guiding vessel axis extraction from gray-scale angiograms: an optimization framework. AB - We propose a novel trace-based method to extract vessel axes from gray-scale angiograms without preliminary segmentations. Our method traces the axes on an optimization framework with the bounded spherical projection images and the sum of squared difference metric. It does not take alternate steps to search the next axial point and its tangent as in other trace-based algorithms, instead the novel method finds the solution simultaneously. This helps avoid U-turns of the trace and large spatial discontinuity of the axial points. Another advantage of the method is that it enables interactive user guidance to produce continuous tracing through regions that contain furcations, disease portions, kissing vessels (vessels in close proximity to each other) and thin vessels, which pose difficulties for the other algorithms and make re-initialization inevitable as illustrated on synthetic and clinical data sets. PMID- 17354895 TI - A statistical parts-based appearance model of inter-subject variability. AB - In this article, we present a general statistical parts-based model for representing the appearance of an image set, applied to the problem of inter subject MR brain image matching. In contrast with global image representations such as active appearance models, the parts-based model consists of a collection of localized image parts whose appearance, geometry and occurrence frequency are quantified statistically. The parts-based approach explicitly addresses the case where one-to-one correspondence does not exist between subjects due to anatomical differences, as parts are not expected to occur in all subjects. The model can be learned automatically, discovering structures that appear with statistical regularity in a large set of subject images, and can be robustly fit to new images, all in the presence of significant inter-subject variability. As parts are derived from generic scale-invariant features, the framework can be applied in a wide variety of image contexts, in order to study the commonality of anatomical parts or to group subjects according to the parts they share. Experimentation shows that a parts-based model can be learned from a large set of MR brain images, and used to determine parts that are common within the group of subjects. Preliminary results indicate that the model can be used to automatically identify distinctive features for inter-subject image registration despite large changes in appearance. PMID- 17354896 TI - The entire regularization path for the support vector domain description. AB - The support vector domain description is a one-class classification method that estimates the shape and extent of the distribution of a data set. This separates the data into outliers, outside the decision boundary, and inliers on the inside. The method bears close resemblance to the two-class support vector machine classifier. Recently, it was shown that the regularization path of the support vector machine is piecewise linear, and that the entire path can be computed efficiently. This paper shows that this property carries over to the support vector domain description. Using our results the solution to the one-class classification can be obtained for any amount of regularization with roughly the same computational complexity required to solve for a particularly value of the regularization parameter. The possibility of evaluating the results for any amount of regularization not only offers more accurate and reliable models, but also makes way for new applications. We illustrate the potential of the method by determining the order of inclusion in the model for a set of corpora callosa outlines. PMID- 17354897 TI - A new closed-form information metric for shape analysis. AB - Shape matching plays a prominent role in the analysis of medical and biological structures. Recently, a unifying framework was introduced for shape matching that uses mixture-models to couple both the shape representation and deformation. Essentially, shape distances were defined as geodesics induced by the Fisher-Rao metric on the manifold of mixture-model represented shapes. A fundamental drawback of the Fisher-Rao metric is that it is NOT available in closed-form for the mixture model. Consequently, shape comparisons are computationally very expensive. Here, we propose a new Riemannian metric based on generalized phi entropy measures. In sharp contrast to the Fisher-Rao metric, our new metric is available in closed-form. Geodesic computations using the new metric are considerably more efficient. Discriminative capabilities of this new metric are studied by pairwise matching of corpus callosum shapes. Comparisons are conducted with the Fisher-Rao metric and the thin-plate spline bending energy. PMID- 17354898 TI - Feasibility of patient specific aortic blood flow CFD simulation. AB - Patient specific modelling of the blood flow through the human aorta is performed using computational fluid dynamics (CFD) and magnetic resonance imaging (MRI). Velocity patterns are compared between computer simulations and measurements. The workflow includes several steps: MRI measurement to obtain both geometry and velocity, an automatic levelset segmentation followed by meshing of the geometrical model and CFD setup to perform the simulations follwed by the actual simulations. The computational results agree well with the measured data. PMID- 17354899 TI - A model based approach for multi-lead ECG array layout selection. AB - In this study an approach for testing electrode array schemes with respect to their ability to improve the resolution of methods for activation time imaging is proposed. First local linear dependency maps are computed using a virtual array method. These maps depict the torso surface areas where the body surface potential is most sensitive to changes in the transmembrane potential. The optimal number and position of the electrodes within the sensitive body surface regions was selected by constructing effort gain (EG) plots. Such a plot depicts the relative attainable rank of the leadfield matrix in relation to the increase in number of electrodes required to build the electrode array. From the sensitivity maps it was found that the BSP is most sensitive to changes in TMP on the upper left frontal and dorsal body surface. The EG analysis revealed that the optimal array meeting clinical requirements and improving the resolution of activation time imaging consists of 125 electrodes. PMID- 17354900 TI - Simulation of acquisition artefacts in MR scans: effects on automatic measures of brain atrophy. AB - Automatic algorithms in conjunction with longitudinal MR brain images can be used to measure cerebral atrophy, which is particularly pronounced in several types of dementia. An atrophy simulation technique has been devised to facilitate validation of these algorithms. To make this model of atrophy more realistic we simulate acquisition artefacts which are common problems in dementia imaging: motion (both step and periodic motion) and pulsatile flow artefact. Artefacts were simulated by combining different portions of k-space from various modified image. The original images were 7 MR scans of healthy elderly controls, each of which had two levels of simulated atrophy. We investigate the effect of the simulated acquisition artefacts in atrophy measurements provided by an automatic technique, SIENA. PMID- 17354901 TI - Non-rigid 2D-3D registration with catheter tip EM tracking for patient specific bronchoscope simulation. AB - This paper investigates the use of Active Shape Models (ASM) to capture the variability of the intra-thoracic airway tree. The method significantly reduces the dimensionality of the non-rigid 2D/3D registration problem and leads to a rapid and robust registration framework. In this study, EM tracking data has been also incorporated through a probabilistic framework for providing a statistically optimal pose given both the EM and the image-based registration measurements. Comprehensive phantom experiments have been conducted to assess the key numerical factors involved in using catheter tip EM tracking for deformable 2D/3D registration. PMID- 17354902 TI - Anatomical modelling of the musculoskeletal system from MRI. AB - This paper presents a novel approach for multi-organ (musculoskeletal system) automatic registration and segmentation from clinical MRI datasets, based on discrete deformable models (simplex meshes). We reduce the computational complexity using multi-resolution forces, multi-resolution hierarchical collision handling and large simulation time steps (implicit integration scheme), allowing real-time user control and cost-efficient segmentation. Radial forces and topological constraints (attachments) are applied to regularize the segmentation process. Based on a medial axis constrained approximation, we efficiently characterize shapes and deformations. We validate our methods for the hip joint and the thigh (20 muscles, 4 bones) on 4 datasets: average error = 1.5 mm, computation time = 15 min. PMID- 17354903 TI - Towards a statistical atlas of cardiac fiber structure. AB - We propose here a framework to build a statistical atlas of diffusion tensors of canine hearts. The anatomical images of seven hearts are first non-rigidly registered in the same reference frame and their associated diffusion tensors are then transformed with a method that preserves the cardiac laminar sheets. In this referential frame, the mean tensor and its covariance matrix are computed based on the Log-Euclidean framework. With this method, we can produce a smooth mean tensor field that is suited for fiber tracking algorithms or the electromechanical modeling of the heart. In addition, by examining the covariance matrix at each voxel it is possible to assess the variability of the cardiac fiber directions and of the orientations of laminar sheets. The results show a strong coherence of the diffusion tensors and the fiber orientations among a population of seven normal canine hearts. PMID- 17354904 TI - A comparison of needle bending models. AB - Modeling the deflection of flexible needles is an essential part of needle insertion simulation and path planning. In this paper, three models are compared in terms of accuracy in simulating the bending of a prostate brachytherapy needle. The first two utilize the finite element method, one using geometric non linearity and triangular plane elements, the other using non-linear beam elements. The third model uses angular springs to model cantilever deflection. The simulations are compared with the experimental bent needle configurations. The models are assessed in terms of geometric conformity using independently identified and pre-identified model parameters. The results show that the angular spring model, which is also the simplest, simulates the needle more accurately than the others. PMID- 17354905 TI - An inverse kinematics model for post-operative knee. Ligament parameters estimation from knee motion. AB - A motion-based Inverse Kinematics Knee (IKK) model was developed for Total Knee Replacement (TKR) joints. By tracking a sequence of passive knee motion, the IKK model estimated ligament properties such as insertion locations. The formulation of the IKK model embedded a Forward Kinematics Knee (FKK) model in a numerical optimization algorithm known as the Unscented Kalman Filter. Simulation results performed on a semi-constrained TKR design suggested that ligament insertions could be accurately estimated in the medial-lateral (ML) and the proximal-distal (PD) directions, but less reliably in the anterior-posterior (AP) direction for the tibial component. However, the forward kinematics produced by both the true and estimated ligament properties were nearly identical, suggesting that the IKK model recovered a kinematically equivalent set of ligament properties. These results imply that it may not be necessary to use a patient-specific CT or MRI scan to locate ligaments, which considerably widens potential applications of kinematic-based total knee replacement. PMID- 17354906 TI - Online parameter estimation for surgical needle steering model. AB - Estimation of the system parameters, given noisy input/output data, is a major field in control and signal processing. Many different estimation methods have been proposed in recent years. Among various methods, Extended Kalman Filtering (EKF) is very useful for estimating the parameters of a nonlinear and time varying system. Moreover, it can remove the effects of noises to achieve significantly improved results. Our task here is to estimate the coefficients in a spring-beam-damper needle steering model. This kind of spring-damper model has been adopted by many researchers in studying the tissue deformation. One difficulty in using such model is to estimate the spring and damper coefficients. Here, we proposed an online parameter estimator using EKF to solve this problem. The detailed design is presented in this paper. Computer simulations and physical experiments have revealed that the simulator can estimate the parameters accurately with fast convergent speed and improve the model efficacy. PMID- 17354907 TI - Realistic simulated MRI and SPECT databases. Application to SPECT/MRI registration evaluation. AB - This paper describes the construction of simulated SPECT and MRI databases that account for realistic anatomical and functional variability. The data is used as a gold-standard to evaluate four SPECT/MRI similarity-based registration methods. Simulation realism was accounted for using accurate physical models of data generation and acquisition. MRI and SPECT simulations were generated from three subjects to take into account inter-subject anatomical variability. Functional SPECT data were computed from six functional models of brain perfusion. Previous models of normal perfusion and ictal perfusion observed in Mesial Temporal Lobe Epilepsy (MTLE) were considered to generate functional variability. We studied the impact noise and intensity non-uniformity in MRI simulations and SPECT scatter correction may have on registration accuracy. We quantified the amount of registration error caused by anatomical and functional variability. Registration involving ictal data was less accurate than registration involving normal data. MR intensity nonuniformity was the main factor decreasing registration accuracy. The proposed simulated database is promising to evaluate many functional neuroimaging methods, involving MRI and SPECT data. PMID- 17354908 TI - Extrapolating tumor invasion margins for physiologically determined radiotherapy regions. AB - In radiotherapy, the constant margin taken around the visible tumor is a very coarse approximation of the invasion margin of cancerous cells. In this article, a new formulation to estimate the invasion margin of a tumor by extrapolating low tumor densities in magnetic resonance images (MRIs) is proposed. The current imaging techniques are able to show parts of the tumor where cancerous cells are dense enough. However, tissue parts containing small number of tumor cells are not enhanced in images. We propose a way to estimate these parts using the tumor mass visible in the image. Our formulation is based on the Fisher-Kolmogorov Equation that is been widely used to model the growth of brain tumors. As a proof of concept, we show some promising preliminary results, which demonstrate the feasibility of the approach. PMID- 17354909 TI - Simultaneous stereoscope localization and soft-tissue mapping for minimal invasive surgery. AB - Minimally Invasive Surgery (MIS) has recognized benefits of reduced patient trauma and recovery time. In practice, MIS procedures present a number of challenges due to the loss of 3D vision and the narrow field-of-view provided by the camera. The restricted vision can make navigation and localization within the human body a challenging task. This paper presents a robust technique for building a repeatable long term 3D map of the scene whilst recovering the camera movement based on Simultaneous Localization and Mapping (SLAM). A sequential vision only approach is adopted which provides 6 DOF camera movement that exploits the available textured surfaces and reduces reliance on strong planar structures required for range finders. The method has been validated with a simulated data set using real MIS textures, as well as in vivo MIS video sequences. The results indicate the strength of the proposed algorithm under the complex reflectance properties of the scene, and the potential for real-time application for integrating with the existing MIS hardware. PMID- 17354910 TI - Real-time endoscopic mosaicking. AB - With the advancement of minimally invasive techniques for surgical and diagnostic procedures, there is a growing need for the development of methods for improved visualization of internal body structures. Video mosaicking is one method for doing this. This approach provides a broader field of view of the scene by stitching together images in a video sequence. Of particular importance is the need for online processing to provide real-time feedback and visualization for image-guided surgery and diagnosis. We propose a method for online video mosaicking applied to endoscopic imagery, with examples in microscopic retinal imaging and catadioptric endometrial imaging. PMID- 17354911 TI - Depth perception--a major issue in medical AR: evaluation study by twenty surgeons. AB - The idea of in-situ visualization for surgical procedures has been widely discussed in the community. While the tracking technology offers nowadays a sufficient accuracy and visualization devices have been developed that fit seamlessly into the operational workflow [1, 3], one crucial problem remains, which has been discussed already in the first paper on medical augmented reality. Even though the data is presented at the correct place, the physician often perceives the spatial position of the visualization to be closer or further because of virtual/real overlay. This paper describes and evaluates novel visualization techniques that are designed to overcome misleading depth perception of trivially superimposed virtual images on the real view. We have invited 20 surgeons to evaluate seven different visualization techniques using a head mounted display (HMD). The evaluation has been divided into two parts. In the first part, the depth perception of each kind of visualization is evaluated quantitatively. In the second part, the visualizations are evaluated qualitatively in regard to user friendliness and intuitiveness. This evaluation with a relevant number of surgeons using a state-of-the-art system is meant to guide future research and development on medical augmented reality. PMID- 17354912 TI - Hybrid navigation interface for orthopedic and trauma surgery. AB - Several visualization methods for intraoperative navigation systems were proposed in the past. In standard slice based navigation, three dimensional imaging data is visualized on a two dimensional user interface in the surgery room. Another technology is the in-situ visualization i.e. the superimposition of imaging data directly into the view of the surgeon, spatially registered with the patient. Thus, the three dimensional information is represented on a three dimensional interface. We created a hybrid navigation interface combining an augmented reality visualization system, which is based on a stereoscopic head mounted display, with a standard two dimensional navigation interface. Using an experimental setup, trauma surgeons performed a drilling task using the standard slice based navigation system, different visualization modes of an augmented reality system, and the combination of both. The integration of a standard slice based navigation interface into an augmented reality visualization overcomes the shortcomings of both systems. PMID- 17354913 TI - Virtual fly-over: a new visualization technique for virtual colonoscopy. AB - In this paper, we propose a new visualization technique for virtual colonoscopy (VC). The proposed method is called Virtual Fly-Over, which splits the entire colon anatomy into exactly two halves. Then, it assigns a virtual camera to each half to perform fly-over navigation, which has several advantages over both traditional fly-through and related methods. First, by controlling the elevation of the camera, there is no restriction on its field of view (FOV) angle (e.g., >90 degrees) to maximize visualized surface areas, and hence no perspective distortion. Second, the camera viewing volume is perpendicular to each colon half, so potential polyps that are hidden behind haustral folds are easily found. Finally, because the orientation of the splitting surface is controllable, the navigation can be repeated at a different split orientation to overcome the problem of having a polyp that is divided between the two halves of the colon. Quantitative experimental results on 15 clinical datasets have shown that the average surface visibility coverage is 99.59 +/- 0.2%. PMID- 17354914 TI - Viscoelasticity modeling of the prostate region using vibro-elastography. AB - We present an ultrasound vibro-elastography system designed to acquire viscoelastic properties of the prostate and peri-prostatic tissue. An excitation stage imparts low-frequency (<20 Hz), limited amplitude (< +/- 2 mm), broadband vibratory motion to an endorectal transducer, along a radial/transversal direction. The induced tissue motion is estimated from ultrasound radio-frequency data and is used to estimate the mechanical frequency response of tissue to the excitation at different spatial locations. This can be used to determine the spatial distribution of various mechanical parameters of tissue, such as stiffness and viscosity. Phantom and in-vivo images are presented. The results obtained demonstrate high phantom and tissue linearity and high signal-to-noise ratio. PMID- 17354915 TI - Simultaneous reconstruction of tissue attenuation and radioactivity maps in SPECT. AB - The importance of accurate attenuation correction in single photon emission computed tomography (SPECT) has been widely recognized. In this paper, we propose a novel scheme of simultaneous reconstruction of the tissue attenuation map and the radioactivity distribution from SPECT emission sinograms, which is obviously beneficial when the transmission data is missing for cost or efficiency reasons. Our strategy combines the SPECT image formation and data measurement models, whereas the attenuation parameters are treated as random variables with known prior statistics. After converting the models to state space representation, the extended Kalman filtering procedures are adopted to linearize the equations and to provide the joint estimates in an approximate optimal sense. Experiments have been performed on synthetic data and real scanning data to illustrate abilities and benefits of the method. PMID- 17354916 TI - Statistical finite element model for bone shape and biomechanical properties. AB - We present a framework for statistical finite element analysis combining shape and material properties, and allowing performing statistical statements of biomechanical performance across a given population. In this paper, we focus on the design of orthopaedic implants that fit a maximum percentage of the target population, both in terms of geometry and biomechanical stability. CT scans of the bone under consideration are registered non-rigidly to obtain correspondences in position and intensity between them. A statistical model of shape and intensity (bone density) is computed by means of principal component analysis. Afterwards, finite element analysis (FEA) is performed to analyse the biomechanical performance of the bones. Realistic forces are applied on the bones and the resulting displacement and bone stress distribution are calculated. The mechanical behaviour of different PCA bone instances is compared. PMID- 17354917 TI - Fetus support manipulator with flexible balloon-based stabilizer for endoscopic intrauterine surgery. AB - A novel manipulator is described for stabilizing fetus and preventing it from free-floating during the endoscopic intrauterine surgery. Minimally invasive endoscopic fetal surgery enables intrauterine intervention with reduced risk to the mother and fetus. We designed and fabricated a prototype of a fetus supporting manipulator equipped with a flexible bending/curving mechanisms and a soft balloon-based stabilizer. The flexible bending and curving mechanisms enable the stabilizer to reach the target sites within the uterus under an ultrasound guidance. The balloon-based stabilizer could be inserted into the uterus with a small incision for entry. The accuracy evaluation showed that the maximum error of the curving mechanism was as small as 7 mm and the standard deviation of the bending mechanism was just 1.6 degrees. In the experiments using a fetus model, the manipulator could be well controlled under ultrasound guidance and its curving mechanism with the balloon-based stabilizer could be clearly visualized during the implementation of fetus model supporting. The manipulator has the potential to be used in minimally invasive intrauterine surgery, though further improvements and experiments remain to be carried out. PMID- 17354918 TI - Recovery of surgical workflow without explicit models. AB - Workflow recovery is crucial for designing context-sensitive service systems in future operating rooms. Abstract knowledge about actions which are being performed is particularly valuable in the OR. This knowledge can be used for many applications such as optimizing the workflow, recovering average workflows for guiding and evaluating training surgeons, automatic report generation and ultimately for monitoring in a context aware operating room. This paper describes a novel way for automatic recovery of the surgical workflow. Our algorithms perform this task without an implicit or explicit model of the surgery. This is achieved by the synchronization of multidimensional state vectors of signals recorded in different operations of the same type. We use an enhanced version of the dynamic time warp algorithm to calculate the temporal registration. The algorithms have been tested on 17 signals of six different surgeries of the same type. The results on this dataset are very promising because the algorithms register the steps in the surgery correctly up to seconds, which is our sampling rate. Our software visualizes the temporal registration by displaying the videos of different surgeries of the same type with varying duration precisely synchronized to each other. The synchronized videos of one surgery are either slowed down or speeded up in order to show the same steps as the ones presented in the videos of the other surgery. PMID- 17354919 TI - Comparison of control modes of a hand-held robot for laparoscopic surgery. AB - Teleoperated robots for minimally invasive surgery make surgeons loose direct contact with the patient. We are developing a handheld, dexterous surgical robot that can be controlled with one hand only, while standing at the operating table. The instrument is composed of a master part (the handle) and a slave part (the tip). This work compares the performance of different control modes, i.e. different ways to map the degrees of freedom of the handle to those of the tip. We ask users to drive the tip along complex trajectories in a virtual environment, using the real master to drive a simulated slave, and assess their performance. Results show that, concerning time, users with no training in laparoscopy prefer a direct mapping of position and orientation, like in free hand motion. However, users trained in laparoscopy perform equally fast with our hand-held robot and, concerning precision, make a smaller number of errors. PMID- 17354920 TI - "Virtual touch": an efficient registration method for catheter navigation in left atrium. AB - In this paper, we present a left atrium registration system which utilizes a 3D intra-cardiac ultrasound catheter for faster (more than 700 times) and higher quality surface registration point collection than current systems and eventually improves the registration accuracy and stability. With better registration our system can greatly improve the ablation catheter navigation system which is being used in many hospitals to guide left atrium endocardium ablation procedure. PMID- 17354921 TI - Towards scarless surgery: an endoscopic-ultrasound navigation system for transgastric access procedures. AB - Scarless surgery is a new and very promising technique that can mark a new era in surgical procedures. We have created and validated a navigation system for endoscopic and transgastric access interventions in in vivo pilot studies. The system provides augmented visual feedback and additional contextual information by establishing a correspondence between the real time endoscopic ultrasound image and a preoperative CT volume using rigid registration. The system enhances the operator's ability to interpret the ultrasound image reducing the mental burden used in probe placement. Our analysis shows that rigid registration is accurate enough to help physicians in endoscopic abdominal surgery where, by using preoperative data for context and real-time imaging for targeting, distortions that limit the use of only preoperative data can be overcome. PMID- 17354922 TI - New 4-D imaging for real-time intraoperative MRI: adaptive 4-D scan. AB - Aiming at real-time 3-D visualization of organ motion to navigate surgical procedures in MRI-guided surgery, a new 4-D MR imaging technique called "Adaptive 4-D Scan" has been proposed. The technique is designed to acquire a time series of volumetric 3-D images (4-D image) of cyclically moving organ, even in a low field open-configuration MR scanner. A pre-operative 4-D image is acquired with respiratory phase parameter, which is monitored by using navigator-echo-based real-time tracking of the liver and diaphragm. During operation, the respiratory phase is again monitored in real-time, and a 3-D image, reflecting the current state of the target organ, is extracted from the pre-operative 4-D image and provided to physicians as a pseudo real-time 3-D image. We implemented Adaptive 4 D Scan into a 0.5 Tesla open-configuration clinical MRI system for intervention. Phantom and volunteer studies were performed to assess feasibility of this technique, in terms of image quality, imaging time and position accuracy of the imaged subject. A 4-D image (matrix: 256 x 128 x 10 x 8) of cyclically moving phantom was acquired in 719 s, and RMS position error between the imaged subject and the real subject was 2.3 mm, where the range of motion was 50 mm. 4-D image of the moving liver was also successfully acquired under near clinical condition. In conclusion, the study shows that the proposed method is feasible and has capability to provide real-time dynamic 3-D atlas for surgical navigation. PMID- 17354923 TI - The use of super resolution in robotic assisted minimally invasive surgery. AB - In minimally invasive surgery, a small field-of-view is often required for achieving a large magnification factor during micro-scale tasks such as coronary anastomosis. Constant change of the orientation and focal length of the laparoscope camera, however, is cumbersome and can impose extra visual and cognitive load to the operating surgeon in realigning the visual pathways and anatomical landmarks. The purpose of this paper is to investigate the use of fixational movements for robotic assisted minimal invasive surgery such that the perceived resolution of the foveal field-of-view is greater than the intrinsic resolution of the laparoscope camera. The proposed technique is based on super resolution imaging using projection onto convex sets. Validation with both phantom and in vivo data from totally endoscopic coronary artery bypass surgery is provided. PMID- 17354924 TI - Modeling the human aorta for MR-driven real-time virtual endoscopy. AB - As interventional magnetic resonance imaging (iMRI) is getting closer to clinical practice, new means of visualization and navigation are required. We present an approach to create a virtual endoscopic view inside the human aorta in real-time. In our approach, defined cross-sectional slices are acquired and segmented in a highly optimized fashion. A geometric shape model is fit to the segmentation points and continuously updated during the intervention. The physician can then view and navigate inside the structure to plan the intervention and get immediate feedback about the procedure. As a component of this system, this work focuses on the segmentation of the cross-sectional images and the fitting of the shape model. We present a real-time 2D segmentation implementation for this application domain and a model fitting scheme for a generalized cylinder (GC) model. For the latter we employ a new scheme for choosing the local reference frame. PMID- 17354925 TI - Adaptive script based animations for intervention planning. AB - We describe scripting facilities to create medical animations for intervention planning based on medical volume data and derived segmentation information. A data independent scripting language has been developed to separate animation scripts from imaging data. The scripting facilities are adaptive and allow to reuse one script to create animations for many different patients. With expressive animations, we support the individual planning process, the preoperative documentation as well as discussions between medical doctors, for example in a tumor board. We also discuss the enhancement of interactive explorations with animations generated on the fly. PMID- 17354926 TI - Towards optimization of probe placement for radio-frequency ablation. AB - We present a model for the optimal placement of mono- and bipolar probes in radio frequency (RF) ablation. The model is based on a numerical computation of the probe's electric potential and of the steady state of the heat distribution during RF ablation. The optimization is performed by minimizing a temperature based objective functional under these constraining equations. The paper discusses the discretization and implementation of the approach. Finally, applications of the optimization to artificial data and a comparison to a real RF ablation are presented. PMID- 17354927 TI - C-arm tracking and reconstruction without an external tracker. AB - For quantitative C-arm fluoroscopy, we have developed a unified mathematical framework to tackle the issues of intra-operative calibration, pose estimation, correspondence and reconstruction, without the use of optical/electromagnetic trackers or precision-made fiducial fixtures. Our method uses randomly distributed unknown points in the imaging volume, either naturally present or induced by randomly sticking beads or other simple markers in the image pace. After these points are segmented, a high dimensional non-linear optimization computes all unknown parameters for calibration, C-arm pose, correspondence and reconstruction. Preliminary phantom experiments indicate an average C-arm tracking accuracy of 0.9 degrees and a 3D reconstruction error of 0.8 mm, with an 80 region of convergence for both the AP and lateral axes. The method appears to be sufficiently accurate for many clinical applications, and appealing since it works without any external instrumentation and does not interfere with the workspace. PMID- 17354928 TI - Rigid-flexible outer sheath model using slider linkage locking mechanism and air pressure for endoscopic surgery. AB - The objective of this paper is to develop an outer sheath for flexible endoscopic manipulators. This sheath can switch two states including flexible and rigid, and make a rigid curved path for inserting manipulators. The flexible mode can be curved into a required shape. The rigid mode can hold the shape of the sheath, and then keep the path for instruments. Through the managed path, the flexible manipulators become easy to reach the target. We proposed a serial multi joint model to realize the flexible mechanism. This model is composed of a set of frame units which are connected serially. Each unit can be rotated to a given angle around the center of the joint. We developed a slider-link mechanism and a gear stopper controlled by air pressure for rigid mode. We designed and fabricated the prototype with a diameter of 16 mm and length of 290 mm. The experiment showed that the device could be switched from the flexible mode to the rigid mode when the air pressure was over 150 kPa, and each joint could hold its angle against the maximum 400 mNm. The phantom experiment showed that the flexible devices are possible to transmit the wire tension to the endpoint of the manipulator without changing the curving shape with by the developed outer sheath device. PMID- 17354929 TI - Combined endo- and exoscopic semi-robotic manipulator system for image guided operations. AB - This paper describes the development of a robotic assistance system for image guided operations. To minimize operation time, a multimodal user interface enables freehand robotic manipulation of an extracorporeal stereoscopic digital camera (exoscope) and an endoscope. The surgeon thereby wears a head-mounted unit with a binocular display, a head tracker, a microphone and earphones. Different view positioning and adjustment modes can be selected by voice and controlled by head rotation while pressing a miniature confirmation button with a finger. Initial studies focused on the evaluation and optimization of the intuitiveness, comfort and precision of different modes of operation, including a user test with neurosurgeons in a virtual reality simulation. The first labtype of the system was then implemented and demonstrated in the operating room on a phantom together with the clinical partners. PMID- 17354930 TI - The feasibility of MR-image guided prostate biopsy using piezoceramic motors inside or near to the magnet isocentre. AB - The excellent soft tissue contrast of Magnetic Resonance Imaging (MRI) has encouraged the development of MRI compatible systems capable of combining the advantages of robotic manipulators with high quality anatomical images. Continuing this development, a new five DOF prostate biopsy manipulator has been designed for use inside a closed 1.5T MRI scanner. Space constraints in the bore and the current trend to restrict field strength exposure for operators indicate that a master-slave configuration is ideal for controlling the robotic system from outside the bore. This system has been designed to work with piezoceramic motors and optical encoders placed inside or near the field of view of the scanner, using real time image guidance for targeting biopsies to specific lesions in the prostate. MRI tests have been performed to prove the feasibility of this concept and a one DOF proof-of-concept test rig implementing closed loop position control has been tested and is presented here. A first prototype of the slave manipulator has been designed and manufactured incorporating this new technology. PMID- 17354931 TI - The role of insertion points in the detection and positioning of instruments in laparoscopy for robotic tasks. AB - In robot-assisted laparoscopic surgery, an endoscopic camera is used to control the motion of surgical instruments. With this minimally invasive surgical (MIS) technique, every instrument has to pass through an insertion point in the abdominal wall and is mounted on the end-effector of a surgical robot which can be controlled by visual feedback. To achieve an accurate vision-based positioning of laparoscopic instruments, we introduce the motion constraint in MIS which is based on the location of out-of-field of view insertion points. The knowledge of the (image of the) insertion point location is helpful for real-time image segmentation issues, particularly to initiate the search for region seeds corresponding to the instruments. Moreover, with this "eye-to-hand" robot vision system, visual servoing is a very convenient technique to automatically guide an instrument but it requires the velocity screw to be expressed in the appropriate frame. Then, the location of the insertion point is seen as the main part of the larger problem of determining the overall transformation between the camera and the robot end-effector frame. This is achieved thanks to a novel algorithm for the pose determination of cylindrical-shaped instruments. With the proposed method, the location of insertion points can be recovered, on-line, with no marker, without any knowledge of robot kinematics and without an external measurement device. PMID- 17354932 TI - Automatic localization of laparoscopic instruments for the visual servoing of an endoscopic camera holder. AB - The use of a robotized camera holder in laparoscopic surgery allows a surgeon to control the endoscope without the intervention of an assistant. Today, the orders that the surgeon can give to robotized camera holders remain limited. In order to provide higher level interactions between the surgeon and a robotized camera holder, we have developed a new method for the automatic tracking of laparoscopic instruments which works in near real-time. The method is based on the measurement of the 3D positions of the insertion points of the instruments in the abdominal cavity and a simple shape model of the laparoscopic instruments. We present the results of our first experimentation on a cadaver. PMID- 17354933 TI - A novel robotic laser ablation system for precision neurosurgery with intraoperative 5-ALA-induced PpIX fluorescence detection. AB - We developed a combined system of tumor detection by 5-ALA-induced PpIX fluorescence and precise ablation by micro laser for the first time, with an automatic focusing and robotic scanning mechanism for the brain surface. 5-ALA accumulates on tumors to be metabolized to become PpIX that is a fluorescent. Intra-operative detection of 5-ALA induced PpIX fluorescence provides useful information for tumor detection. The wavelength of the micro laser is 2.8 microm close to the absorption band of water. This laser is effective only on the surface of brain tissue, enabling precise ablation at the boundary between tumor and normal tissue identified by intra-operative 5-ALA induced fluorescence. Combination tests of the fluorescence measurement and the laser ablation were performed, and it was possible to extract the area with fluorescence appropriately from the measurement data, and the micro laser with automatically scanning selectively ablated the extracted area. PMID- 17354934 TI - Visual servoing for intraoperative positioning and repositioning of mobile C arms. AB - The problem of positioning mobile C-arms, e.g. for down the beam techniques, as well as repositioning during surgical procedures currently requires time, skill and additional radiation. This paper uses a Camera-Augmented Mobile C-arm (CAMC) to speed up the procedure, simplify its execution and reduce the necessary radiation. For positioning the C-arm in down-the-beam position, the pre-operative diagnostic CT is used for defining the axis. Additional CT visible markers on patient's skin allow the CAMC's optical camera to compute the C-arm's pose and its required displacement for positioning. In the absence of electronically controlled mobile C-arms, the system provides step-by-step guidance to surgical staff until the final position is achieved. At this point, the surgeon can acquire an X-ray to ensure the correct positioning. In the case of intra operative repositioning, no pre-operative CT is required. X-ray/Optical markers allow the visual servoing algorithm to guide the surgical staff in C-arm repositioning using CAMC's optical camera. This work paves the path for many possible applications of visual servoing in C-arm positioning and in surgical navigation. Experiments on phantom and a cadaver study demonstrate the advantages of the new methods. PMID- 17354935 TI - Navigated three dimensional beta probe for optimal cancer resection. AB - In minimally invasive tumor resection, the desirable goal is to perform a minimal but complete removal of cancerous cells. In the last decades interventional nuclear medicine probes supported the detection of remaining tumor cells. However, scanning the patient with an intraoperative probe and applying the treatment are not done simultaneously. The main contribution of this work is to extend the one dimensional signal of a beta-probe to a four dimensional signal including the spatial information of the distal end of the probe. We generate a color encoded surface map of the scanned activity and guide any tracked surgical instrument back to the regions with measured activity. For navigation, we implement an augmented reality visualization that superimposes the acquired surface on a visual image of the real anatomy. Alternatively, a simulated beta probe count rate in the tip of a tracked therapeutic instrument is simulated showing the count number and coding it as an acoustic signal. Preliminary tests were performed showing the feasibility of the new designed system and the viability of such a three dimensional intraoperative molecular imaging modality. PMID- 17354936 TI - Development of safe mechanism for surgical robots using equilibrium point control method. AB - This paper introduces a novel mechanism for surgical robotic systems to generate human arm-like compliant motion. The mechanism is based on the idea of the equilibrium point control hypothesis which claims that multi-joint limb movements are achieved by shifting the limbs' equilibrium positions defined by neuromuscular activity. The equilibrium point control can be implemented on a robot manipulator by installing two actuators at each joint of the manipulator, one to control the joint position, and the other to control the joint stiffness. This double-actuator mechanism allows us to arbitrarily manipulate the stiffness (or impedance) of a robotic manipulator as well as its position. Also, the force at the end-effector can be estimated based on joint stiffness and joint angle changes without using force transducers. A two-link manipulator and a three-link manipulator with the double-actuator units have been developed, and experiments and simulation results show the potential of the proposed approach. By creating the human arm-like behavior, this mechanism can improve the performance of robot manipulators to execute stable and safe movement in surgical environments by using a simple control scheme. PMID- 17354937 TI - Real time adaptive filtering for digital X-ray applications. AB - Over the last decade, many methods for adaptively filtering a data stream have been proposed. Those methods have applications in two dimensional imaging as well as in three dimensional image reconstruction. Although the primary objective of this filtering technique is to reduce the noise while avoiding to blur the edges, diagnostic, automated segmentation and surgery show a growing interest in enhancing the features contained in the image flow. Most of the methods proposed so far emerged from thorough studies of the physics of the considered modality and therefore show only a marginal capability to be extended across modalities. Moreover, adaptive filtering belongs to the family of processing intensive algorithms. Existing technology has often driven to simplifications and modality specific optimization to sustain the expected performances. In the specific case of real time digital X-ray as used surgery, the system has to sustain a throughput of 30 frames per second. In this study, we take a generalized approach for adaptive filtering based on multiple oriented filters. Mapping the filtering part to the embedded real time image processing while a user/application defined adaptive recombination of the filter outputs allow to change the smoothing and edge enhancement properties of the filter without changing the oriented filter parameters. We have implemented the filtering on a Cell Broadband Engine processor and the adaptive recombination on an off-the-shelf PC, connected via Gigabit Ethernet. This implementation is capable of filtering images of 5122 pixels at a throughput in excess of 40 frames per second while allowing to change the parameters in real time. PMID- 17354938 TI - Semiautomatic volume conductor modeling pipeline for imaging the cardiac electrophysiology noninvasively. AB - In this paper we present an approach for extracting patient individual volume conductor models (VCM) using volume data acquired from Magnetic Resonance Imaging (MRI) for computational biology of electrical excitation in the patient's heart. The VCM consists of the compartments chest surface, lung surfaces, the atrial and ventricular myocardium, and the blood masses. For each compartment a segmentation approach with no or little necessity of user interaction was implemented and integrated into a VCM segmentation pipeline to enable the inverse problem of electrocardiography to become clinical applicable. The segmentation pipeline was tested using volume data from ten patients with structurally normal hearts. PMID- 17354939 TI - Atrial septal defect tracking in 3D cardiac ultrasound. AB - We are working to develop beating-heart atrial septal defect (ASD) closure techniques using real-time 3-D ultrasound guidance. The major image processing challenges are the low image quality and the high frame rate. This paper presents comparative results for ASD tracking in sequences of 3D cardiac ultrasound. We introduce a block flow technique, which combines the velocity computation from optical flow for an entire block with template matching. Enforcing similarity constraints to both the previous and first frames ensures optimal and unique solutions. We compare the performance of the proposed algorithm with that of block matching and optical flow on six in-vivo 4D datasets acquired from porcine beating-heart procedures. Results show that our technique is more stable and has higher sensitivity than both optical flow and block matching in tracking ASDs. Computing velocity at the block level, our technique is much faster than optical flow and comparable in computation cost to block matching. PMID- 17354940 TI - Intra-operative volume imaging of the left atrium and pulmonary veins with rotational X-ray angiography. AB - Complex electrophysiology (EP) procedures, such as catheter-based ablation in the left atrium and pulmonary veins (LAPV) for treatment of atrial fibrillation, require knowledge of heart chamber anatomy. Electroanatomical mapping (EAM) is typically used to define cardiac structures by combining electromagnetic spatial catheter localization with surface models which interpolate the anatomy between EAM point locations in 3D. Recently, the incorporation of pre-operative volumetric CT or MR data sets has allowed for more detailed maps of LAPV anatomy to be used intra-operatively. Preoperative data sets are however a rough guide since they can be acquired several days to weeks prior to EP intervention. Due to positional and physiological changes, the intra-operative cardiac anatomy can be different from that depicted in the pre-operative data. We present a novel application of contrast-enhanced rotational X-ray imaging for CT-like reconstruction of 3D LAPV anatomy during the intervention itself. We perform two selective contrast-enhanced rotational acquisitions and reconstruct CT-like volumes with 3D filtered back projection. Two volumes depicting the left and right portions of the LAPV are registered and fused. The combined data sets are then visualized and segmented intra-procedurally to provide anatomical data and surface models for intervention guidance. Our results from animal and human experiments indicate that the anatomical information from intra-operative CT-like reconstructions compares favorably with pre-acquired CT data and can be of sufficient quality for intra-operative guidance. PMID- 17354942 TI - Carotid artery segmentation using an outlier immune 3D active shape models framework. AB - This paper presents an outlier immune 3D active shape models framework for robust volumetric segmentation of the carotid artery required for accurate plaque burden assessment. In the proposed technique, outlier handling is based on a shape metric that is invariant to scaling, rotation and translation by using the ratio of inter-landmark distances as a local shape dissimilarity measure. Tolerance intervals for each descriptor are calculated from the training samples and used to infer the validity of landmarks. The identified outliers are corrected prior to the model fitting using the ratios distributions and appearance information. To improve the feature point search, the method exploits the geometrical knowledge from the outlier analysis at the previous iteration to weight the gray level appearance based fitness measure. A combined intensity-phase feature point search is also introduced which significantly limits the presence of outliers and improves the overall search accuracy. Both numerical and in vivo assessments of the method involving volumetric segmentation of the carotid artery have shown that the outlier handling technique is capable of handling a significant presence of outliers independently of the amplitudes. PMID- 17354941 TI - Phase-based registration of multi-view real-time three-dimensional echocardiographic sequences. AB - Real time three-dimensional echocardiography opens the possibility of interactive, fast three-dimensional analysis of cardiac anatomy and function. However, at the present time these capabilities cannot be fully exploited due to the low image quality associated to this modality. We propose to increase image quality and information content by combining images acquired from different echocardiographic windows. In this paper, we present an algorithm to register these datasets. Phase-based measures have been proposed as a suitable alternative to intensity-based ones for ultrasound image analysis. The proposed algorithm uses a new cost function, based on local orientation and phase differences, to align the datasets. Visual observation of results, and preliminary numerical analysis, show the robustness and accuracy of this method. PMID- 17354943 TI - Estimation of cardiac hyperelastic material properties from MRI tissue tagging and diffusion tensor imaging. AB - The passive material properties of myocardium are important in the understanding of diastolic cardiac dysfunction. We determined hyperelastic myocardial material parameters in four isolated arrested pig hearts undergoing passive inflation of the left ventricle. Using geometry from MRI, recorded boundary conditions, muscle fiber architecture from diffusion tensor imaging, and deformation from tissue tagging, finite element models were constructed to solve the finite elasticity stress estimation problem. The constitutive parameters of a hyperelastic transversely isotropic material law were determined by minimizing the difference between the predicted and imaged deformation field. The optimized parameters were in a similar range as those reported by previous studies, showing increased passive stiffness in the muscle fiber direction. The average RMS error was 0.92 mm, similar to the image resolution of 0.80 mm. Optimization of hyperelastic models of myocardial mechanics can thus be performed to extract meaningful biophysical parameters from MRI data. PMID- 17354944 TI - Boosting and nonparametric based tracking of tagged MRI cardiac boundaries. AB - In this paper we present an accurate cardiac boundary tracking method for 2D tagged MRI time sequences. This method naturally integrates the motion and the static local appearance features and generates accurate boundary criteria via a boosting approach. We extend the conventional Adaboost classifier into a posterior probability form, which can be embedded in a particle filtering-based shape tracking framework. To make the tracking process more robust and faster, we use a PCA subspace shape representation to constrain the shape variation and lower the dimensionality. We also learn two shape-dynamic models for systole and diastole separately, to predict the shape evolution. Our tracking method incorporates the static appearance, the motion appearance, the shape constraints, and the dynamic prediction in a unified way. The proposed method has been implemented on 50 tagged MRI sequences. The experimental results show the accuracy and robustness of our approach. PMID- 17354945 TI - A region based algorithm for vessel detection in retinal images. AB - Accurate retinal blood vessel detection offers a great opportunity to predict and detect the stages of various ocular and systemic diseases, such as glaucoma, hypertension and congestive heart failure, since the change in width of blood vessels in retina has been reported as an independent and significant prospective risk factor for such diseases. In large-population studies of disease control and prevention, there exists an overwhelming need for an automatic tool that can reliably and accurately identify and measure retinal vessel diameters. To address requirements in this clinical setting, a vessel detection algorithm is proposed to quantitatively measure the salient properties of retinal vessel and combine the measurements by Bayesian decision to generate a confidence value for each detected vessel segment. The salient properties of vessels provide an alternative approach for retinal vessel detection at a level higher than detection at the pixel level. Experiments show superior detection performance than currently published results using a publicly available data set. More importantly, the proposed algorithm provides the confidence measurement that can be used as an objective criterion to select reliable vessel segments for diameter measurement. PMID- 17354946 TI - Carotid artery and jugular vein tracking and differentiation using spatiotemporal analysis. AB - We have derived and evaluated parameters from ultrasound images of the neck to permit a computer to automatically characterize and differentiate between the carotid artery and jugular vein at image acquisition time during vascular interventions, given manually placed seed points. Our goal is to prevent inadvertent damage to the carotid artery when targeting the jugular vein for catheterization. We used a portable 10 MHz ultrasound system to acquire cross sectional B-mode ultrasound images of these great vessels at 10 fps. An expert user identified the vessels in the first frame by touching the vessels on the screen with his fingertip, and the computer automatically tracked the vessels and calculated a best-fit ellipse for each vessel in each subsequent frame. Vessel location and radii were further analyzed to produce parameters that proved useful for differentiating between the carotid artery and jugular vein. These parameters include relative location of the vessels, distension of the vessel walls, and consistent phase difference between the arterial and venous pulsations as determined by temporal Fourier analysis. PMID- 17354947 TI - Appearance models for robust segmentation of pulmonary nodules in 3D LDCT chest images. AB - To more accurately separate each pulmonary nodule from its background in a low dose computer tomography (LDCT) chest image, two new adaptive probability models of visual appearance of small 2D and large 3D pulmonary nodules are used to control evolution of deformable boundaries. The appearance prior is modeled with a translation and rotation invariant Markov-Gibbs random field of voxel intensities with pairwise interaction analytically identified from a set of training nodules. Appearance of the nodules and their background in a current multi-modal chest image is also represented with a marginal probability distribution of voxel intensities. The nodule appearance model is isolated from the mixed distribution using its close approximation with a linear combination of discrete Gaussians. Experiments with real LDCT chest images confirm high accuracy of the proposed approach. PMID- 17354948 TI - Intensity-based volumetric registration of contrast-enhanced MR breast images. AB - In this paper, we propose a fast intensity-based registration algorithm for the analysis of contrast-enhanced breast MR images. Motion between pre-contrast and post-contrast images has been modeled by a combination of rigid transformation and free-form deformation. By modeling the conditional probability function to be Gaussian and considering the normalized mutual information (NMI) criterion, we create a pair of auxiliary images to speed up the registration process. The auxiliary images are registered to the actual images by optimizing the simple sum of squared difference (SSD) criterion. The overall registration is achieved by linearly combining the deformation observed in the auxiliary images. One well known problem of non-rigid registration of contrast enhanced images is the contraction of enhanced lesion volume. We address this problem by rejecting the intensity outliers from registration. Results have shown that our method could achieve accurate registration of the data while successfully prevent the contraction of the contrast enhanced lesion volume. PMID- 17354949 TI - Semi-parametric analysis of dynamic contrast-enhanced MRI using Bayesian P splines. AB - Current approaches to quantitative analysis of DCE-MRI with non-linear models involve the convolution of an arterial input function (AIF) with the contrast agent concentration at a voxel or regional level. Full quantification provides meaningful biological parameters but is complicated by the issues related to convergence, (de-)convolution of the AIF, and goodness of fit. To overcome these problems, this paper presents a penalized spline smoothing approach to model the data in a semi-parametric way. With this method, the AIF is convolved with a set of B-splines to produce the design matrix, and modeling of the resulting deconvolved biological parameters is obtained in a way that is similar to the parametric models. Further kinetic parameters are obtained by fitting a non linear model to the estimated response function and detailed validation of the method, both with simulated and in vivo data is PMID- 17354950 TI - Segmentation of brain MRI in young children. AB - This paper describes an automatic tissue segmentation algorithm for brain MRI of young children. Existing segmentation methods developed for the adult brain do not take into account the specific tissue properties present in the brain MRI of young children. We examine the suitability of state-of-the-art methods developed for the adult brain when applied to the segmentation of the young child brain MRI. We develop a method of creation of a population-specific atlas from young children using a single manual segmentation. The method is based on non-linear propagation of the segmentation into population and subsequent affine alignment into a reference space and averaging. Using this approach we significantly improve the performance of the popular EM segmentation algorithm on brain MRI of young children. PMID- 17354951 TI - A learning based algorithm for automatic extraction of the cortical sulci. AB - This paper presents a learning based method for automatic extraction of the major cortical sulci from MRI volumes or extracted surfaces. Instead of using a few pre defined rules such as the mean curvature properties, to detect the major sulci, the algorithm learns a discriminative model by selecting and combining features from a large pool of candidates. We used the Probabilistic Boosting Tree algorithm to learn the model, which implicitly discovers and combines rules based on manually annotated sulci traced by neuroanatomists. The algorithm almost has no parameters to tune and is fast because of the adoption of integral volume and 3D Haar filters. For a given approximately registered MRI volume, the algorithm computes the probability of how likely it is that each voxel lies on a major sulcus curve. Dynamic programming is then applied to extract the curve based on the probability map and a shape prior. Because the algorithm can be applied to MRI volumes directly, there is no need to perform preprocessing such as tissue segmentation or mapping to a canonical space. The learning aspect makes the approach flexible and it also works on extracted cortical surfaces. PMID- 17354952 TI - Probabilistic brain atlas encoding using Bayesian inference. AB - This paper addresses the problem of creating probabilistic brain atlases from manually labeled training data. We propose a general mesh-based atlas representation, and compare different atlas models by evaluating their posterior probabilities and the posterior probabilities of their parameters. Using such a Baysian framework, we show that the widely used "average" brain atlases constitute relatively poor priors, partly because they tend to overfit the training data, and partly because they do not allow to align corresponding anatomical features across datasets. We also demonstrate that much more powerful representations can be built using content-adaptive meshes that incorporate non rigid deformation field models. We believe extracting optimal prior probability distributions from training data is crucial in light of the central role priors play in many automated brain MRI analysis techniques. PMID- 17354953 TI - Atlas stratification. AB - The process of constructing an atlas typically involves selecting one individual from a sample on which to base or root the atlas. If the individual selected is far from the population mean, then the resulting atlas is biased towards this individual. This, in turn, can bias any inferences made with the atlas. Unbiased atlas construction addresses this issue by either basing the atlas on the individual which is the median of the sample or by an iterative technique whereby the atlas converges to the unknown population mean. In this paper, we explore the question of whether a single atlas is appropriate for a given sample or whether there is sufficient image based evidence from which we can infer multiple atlases, each constructed from a subset of the data. We refer to this process as atlas stratification. Essentially, we determine whether the sample, and hence the population, is multi-modal and is best represented by an atlas per mode. We use the mean shift algorithm to identify the modes of the sample and multidimensional scaling to visualize the clustering process. PMID- 17354954 TI - Physiome model based state-space framework for cardiac kinematics recovery. AB - In order to more reliably recover cardiac information from noise-corrupted patient-specific measurements, it is essential to employ meaningful a priori constraining models and adopt appropriate optimization criteria to couple the models with the measurements. While biomechanical models have been extensively used for myocardial motion recovery with encouraging results, the passive nature of such constraints limits their ability to fully count for the deformation caused by active forces of the myocytes. To overcome such limitations, we propose to adopt a cardiac physiome model as the prior constraint for heart motion analysis. The model is comprised of a cardiac electric wave propagation model, an electromechanical coupling model, and a biomechanical model, and thus more completely describes the macroscopic cardiac physiology. Embedded within a multiframe state-space framework, the uncertainties of the model and the patient specific measurements are systematically dealt with to arrive at optimal estimates of the cardiac kinematics and possibly beyond. Experiments have been conducted on synthetic data and MR image sequences to illustrate its abilities and benefits. PMID- 17354955 TI - Automated detection of left ventricle in 4D MR images: experience from a large study. AB - We present a fully automated method to estimate the location and orientation of the left ventricle (LV) in four-dimensional (4D) cardiac magnetic resonance (CMR) images without any user input. The method is based on low-level image processing techniques incorporating anatomical knowledge and is able to provide rapid, robust feedback for automated scan planning or further processing. The method relies on a novel combination of temporal Fourier analysis of image cines with simple contour detection to achieve a fast localization of the heart. Quantitative validation was performed using 4D CMR datasets from 330 patients (54024 images) with a range of cardiac and vascular disease by comparing manual location with the automatic results. The method failed on one case, and showed average bias and precision of under 5mm in apical, mid-ventricular and basal slices in the remaining 329. The errors in automatic orientation were similar to the errors in scan planning as performed by experienced technicians. PMID- 17354956 TI - Pairwise active appearance model and its application to echocardiography tracking. AB - We propose a pairwise active appearance model (PAAM) to characterize statistical regularities in shape, appearance, and motion presented by a target that undergoes a series of motion phases, such as the left ventricle in echocardiography. The PAAM depicts the transition in motion phase through a Markov chain and the transition in both shape and appearance through a conditional Gaussian distribution. We learn from a database the joint Gaussian distribution of the shapes and appearances belonging to two consecutive motion phases (i.e., a pair of motion phases), from which we analytically compute the conditional Gaussian distribution. We utilize the PAAM in tracking the left ventricle contour in echocardiography and obtain improved tracking results in terms of localization accuracy when compared with expert-specified contours. PMID- 17354957 TI - Cardiac motion recovery: continuous dynamics, discrete measurements, and optimal estimation. AB - A sampled-data filtering framework is presented for cardiac motion recovery from periodic medical image sequences. Cardiac dynamics is a continuously evolving physiological process, whereas the imaging data can provide only sampled measurements at discrete time instants. Stochastic multi-frame filtering frameworks are constructed to couple the continuous cardiac dynamics with the discrete measurements, and to deal with the parameter uncertainty of the biomechanical constraining model and the noisy nature of the imaging data in a coordinated fashion. The state estimates are predicted according to the continuous-time state equation between observation time points, and then updated with the new measurements obtained at discrete time instants, yielding physically more meaningful and more accurate estimation results. Both continuous-discrete Kalman filter and sampled-data Hinfinity filter are applied, and the Hinfinity scheme can give robust estimation results when the noise statistics is not available a priori. The sampled-data estimation strategies are validated through synthetic data experiments to illustrate their advantages and on canine MR phase contrast images to show their clinical relevance. PMID- 17354958 TI - HMM assessment of quality of movement trajectory in laparoscopic surgery. AB - Laparoscopic surgery poses many different constraints to the operating surgeon, this has resulted in a slow uptake of advanced laparoscopic procedures. Traditional approaches to the assessment of surgical performance rely on prior classification of a cohort of surgeons' technical skills for validation, which may introduce subjective bias to the outcome. In this study, Hidden Markov Models (HMMs) are used to learn surgical maneuvers from 11 subjects with mixed abilities. By using the leave-one-out method, the HMMs are trained without prior clustering subjects into different skills levels, and the output likelihood indicates the similarity of a particular subject's motion trajectories to the group. The experimental results demonstrate the strength of the method in ranking the quality of trajectories of the subjects, highlighting its value in minimizing the subjective bias in skills assessment for minimally invasive surgery. PMID- 17354959 TI - A novel MRI texture analysis of demyelination and inflammation in relapsing remitting experimental allergic encephalomyelitis. AB - We have developed a novel multiscale localized image texture analysis technique, based upon the polar Stockwell Transform (PST). In this paper we characterized image texture in vivo using the PST in histologically verified lesion areas in T2 weighted MRI of an animal model of multiple sclerosis. Both high and low frequency signals, representing inflammation and demyelination, were significantly increased in pathological regions compared to normal control tissue. This suggests that this new local spatial-frequency measure of image texture may provide a sensitive and precise indication of disease activity. PMID- 17354960 TI - Comparison of different targeting methods for subthalamic nucleus deep brain stimulation. AB - The subthalamic nucleus (STN) has been adopted as a commonly used surgical target in deep brain stimulation (DBS) procedures for the treatment of Parkinson's disease. Many techniques have been developed to facilitate STN DBS targeting, and consequently to improve the surgical outcome. In this work, we conducted a retrospective study on 10 patients who were treated with bilateral STN DBS to assess the target localization accuracy and precision of six methods in STN DBS surgery. A visualization and navigation system integrated with normalized functional and anatomical information was employed to perform the targeting procedures. Actual surgical target location determined by an experienced neurosurgeon with pre-operative image-guided surgical target/trajectory planning and intra-operative electrophysiological exploration and confirmation was considered as the "gold standard" in this evaluation and was compared with those localized using each of the six targeting methods. The mean distance between the actual surgical targets and those planned was 3.0 +/- 1.3 mm, 3.2 +/- 1.1 mm, 2.9 +/- 1.1 mm, 2.7 +/- 1.2 mm, 2.5 +/- 1.0 mm, and 1.7 +/- 0.8 mm for targeting approaches based on T2-weighted magnetic resonance image (MRI), brain atlas, T1 and T2 maps, electrophysiological database, collection of final surgical targets of previous patients, and the combination of these functional and anatomical data respectively. The results demonstrated that the use of functional data along with anatomical data provides reliable and accurate target position for STN DBS. PMID- 17354961 TI - Objective outcome evaluation of breast surgery. AB - A new method is proposed to unambiguously define a geometric partitioning of 3D models of female thorax. A breast partitioning scheme is derived from simple geometric primitives and well-defined anatomical points. Relevant measurements can be extrapolated from breast partition. Our method has been tested on a number of breast 3D models acquired by means of a commercial scanner on real clinical cases. PMID- 17354962 TI - Automatic detection and segmentation of ground glass opacity nodules. AB - Ground Glass Opacity (GGO) is defined as hazy increased attenuation within a lung that is not associated with obscured underlying vessels. Since pure (nonsolid) or mixed (partially solid) GGO at the thin-section CT are more likely to be malignant than those with solid opacity, early detection and treatment of GGO can improve a prognosis of lung cancer. However, due to indistinct boundaries and inter- or intra-observer variation, consistent manual detection and segmentation of GGO have proved to be problematic. In this paper, we propose a novel method for automatic detection and segmentation of GGO from chest CT images. For GGO detection, we develop a classifier by boosting k-NN whose distance measure is the Euclidean distance between the nonparametric density estimates of two examples. The detected GGO region is then automatically segmented by analyzing the texture likelihood map of the region. We applied our method to clinical chest CT volumes containing 10 GGO nodules. The proposed method detected all of the 10 nodules with only one false positive nodule. We also present the statistical validation of the proposed classifier for GGO detection as well as very promising results for automatic GGO segmentation. The proposed method provides a new powerful tool for automatic detection as well as accurate and reproducible segmentation of GGO. PMID- 17354963 TI - Imaging of 3D cardiac electrical activity: a model-based recovery framework. AB - We present a model-based framework for imaging 3D cardiac transmembrane potential (TMP) distributions from body surface potential (BSP) measurements. Based on physiologically motivated modeling of the spatiotemporal evolution of TMPs and their projection to body surface, the cardiac electrophysiology is modeled as a stochastic system with TMPs as the latent dynamics and BSPs as external measurements. Given the patient-specific data from BSP measurements and tomographic medical images, the inverse problem of electrocardiography (IECG) is solved via state estimation of the underlying system, using the unscented Kalman filtering (UKF) for data assimilation. By incorporating comprehensive a priori physiological information, the framework enables direct recovery of intracardiac electrophysiological events free from commonly used physical equivalent cardiac sources, and delivers accurate, robust, and fast converging results under different noise levels and types. Experiments concerning individual variances and pathologies are also conducted to verify its feasibility in patient-specific applications. PMID- 17354964 TI - Segmentation of the surfaces of the retinal layer from OCT images. AB - We have developed a method for the automated segmentation of the internal limiting membrane and the pigment epithelium in 3-D OCT retinal images. Each surface was found as a minimum s-t cut from a geometric graph constructed from edge/regional information and a priori-determined surface constraints. Our approach was tested on 18 3-D data sets (9 from patients with normal optic discs and 9 from patients with papilledema) obtained using a Stratus OCT-3 scanner. Qualitative analysis of surface detection correctness indicates that our method consistently found the correct surfaces and outperformed the proprietary algorithm used in the Stratus OCT-3 scanner. For example, for the internal limiting membrane, 4% of the 2-D scans had minor failures with no major failures using our approach, but 19% of the 2-D scans using the Stratus OCT-3 scanner had minor or complete failures. PMID- 17354965 TI - Spinal crawlers: deformable organisms for spinal cord segmentation and analysis. AB - Spinal cord analysis is an important problem relating to the study of various neurological diseases. We present a novel approach to spinal cord segmentation in magnetic resonance images. Our method uses 3D "deformable organisms" (DefOrg) an artificial life framework for medical image analysis that complements classical deformable models (snakes and deformable meshes) with high-level, anatomically driven control mechanisms. The DefOrg framework allows us to model the organism's body as a growing generalized tubular spring-mass system with an adaptive and predominantly elliptical cross section, and to equip them with spinal cord specific sensory modules, behavioral routines and decision making strategies. The result is a new breed of robust DefOrgs, "spinal crawlers", that crawl along spinal cords in 3D images, accurately segmenting boundaries, and providing sophisticated, clinically-relevant structural analysis. We validate our method through the segmentation of spinal cords in clinical data and provide comparisons to other segmentation techniques. PMID- 17354966 TI - Markerless endoscopic registration and referencing. AB - Accurate patient registration and referencing is a key element in navigated surgery. Unfortunately all existing methods are either invasive or very time consuming. We propose a fully non-invasive optical approach using a tracked monocular endoscope to reconstruct the surgical scene in 3D using photogrammetric methods. The 3D reconstruction can then be used for matching the pre-operative data to the intra-operative scene. In order to cope with the near real-time requirements for referencing, we use a novel, efficient 3D point management method during 3D model reconstruction. The presented prototype system provides a reconstruction accuracy of 0.1 mm and a tracking accuracy of 0.5 mm on phantom data. The ability to cope with real data is demonstrated by cadaver experiments. PMID- 17354967 TI - Real-time tracking of contrast bolus propagation in continuously moving table MR angiography. AB - The recent introduction of variable-velocity control for Continuously Moving Table Magnetic Resonance Imaging has introduced the ability for interactive examination across extended fields of view. A common application of this method is contrast-enhanced angiography, where propagation of an intravenously injected contrast agent is tracked throughout the peripheral vascular tree. Whereas current methods for performing contrast bolus tracking are entirely manual, we discuss the complete automation of this process through the use of real-time image processing. Specifically, we provide a coupled intensity-correction procedure and modified Fast Marching method for rapid segmentation of contrast enhanced vasculature in CE-MRA and discuss the incorporation of this process into a framework for fully automated and adaptive control of table motion for real time tracking of contrast bolus propagation through the lower peripheral vasculature. PMID- 17354968 TI - Preventing signal degradation during elastic matching of noisy DCE-MR eye images. AB - Motion during the acquisition of dynamic contrast enhanced MRI can cause model fitting errors requiring co-registration. Clinical implementations use a pharmacokinetic model to determine lesion parameters from the contrast passage. The input to the model is the time-intensity plot from a region of interest (ROI) covering the lesion extent. Motion correction meanwhile involves interpolation and smoothing operations thereby affecting the time-intensity plots. This paper explores the trade-offs in applying an elastic matching procedure on the lesion detection and proposes enhancements. The method of choice is the 3D realization of the Demon's elastic matching procedure. We validate our enhancements using synthesized deformation of stationary datasets that also serve as ground-truth. The framework is tested on 42 human eye datasets. Hence, we show that motion correction is beneficial in improving the model-fit and yet needs enhancements to correct for the intensity reductions during parameter estimation. PMID- 17354969 TI - Automated analysis of the mitotic phases of human cells in 3D fluorescence microscopy image sequences. AB - The evaluation of fluorescence microscopy images acquired in high-throughput cell phenotype screens constitutes a substantial bottleneck and motivates the development of automated image analysis methods. Here we introduce a computational scheme to process 3D multi-cell time-lapse images as they are produced in large-scale RNAi experiments. We describe an approach to automatically segment, track, and classify cell nuclei into different mitotic phases. This enables automated analysis of the duration of single phases of the cell life cycle and thus the identification of cell cultures that show an abnormal mitotic behavior. Our scheme proves a high accuracy, suggesting a promising future for automating the evaluation of high-throughput experiments. PMID- 17354970 TI - Spline-based probabilistic model for anatomical landmark detection. AB - In medical imaging, finding landmarks that provide biologically meaningful correspondences is often a challenging and time-consuming manual task. In this paper we propose a generic and simple algorithm for landmarking non-cortical brain structures automatically. We use a probabilistic model of the image intensities based on the deformation of a tissue probability map, learned from a training set of hand-landmarked images. In this setting, estimating the location of the landmarks in a new image is equivalent to finding, by likelihood maximization, the "best" deformation from the tissue probability map to the image. The resulting algorithm is able to handle arbitrary types and numbers of landmarks. We demonstrate our algorithm on the detection of 3 landmarks of the hippocampus in brain MR images. PMID- 17354971 TI - Affine and deformable registration based on polynomial expansion. AB - This paper presents a registration framework based on the polynomial expansion transform. The idea of polynomial expansion is that the image is locally approximated by polynomials at each pixel. Starting with observations of how the coefficients of ideal linear and quadratic polynomials change under translation and affine transformation, algorithms are developed to estimate translation and compute affine and deformable registration between a fixed and a moving image, from the polynomial expansion coefficients. All algorithms can be used for signals of any dimensionality. The algorithms are evaluated on medical data. PMID- 17354972 TI - Simultaneous multiple image registration method for T1 estimation in breast MRI images. AB - The estimation and subsequent use of tissue T1(x) parameters at each image location x can potentially lead to a more reliable classification of breast tissues. T1 values can be estimated using multiple (typically 3) MRI images of different flip angles. However, breathing and other slight movements can render the highly non-linear estimation procedure error-prone. In this paper, a simultaneous multiple image registration method is proposed to solve this problem. The registration method is built upon the idea of conserving inverse consistency and transitivity among the multiple image transformations. The algorithm is applied to both simulated data and real breast MRI images. The performance is compared with existing pairwise image registration method. The results clearly indicate that the simultaneous multiple image registration algorithm leads to much more accurate T1 estimation. PMID- 17354973 TI - New CTA protocol and 2D-3D registration method for liver catheterization. AB - 2D-3D registration for angiographic liver interventions is an unsolved problem mainly because of two reasons. First, a suitable protocol for Computed Tomography Angiography (CTA) to contrast liver arteries is not used in clinical practice. Second, an adequate registration algorithm which addresses the difficult task of aligning deformed vessel structures has not been developed yet. We address the first issue by introducing an angiographic CT scanning phase and thus create a strong link between radiologists and interventionalists. The scan visualizes arteries similar to the vasculature captured with an intraoperative C-arm acquiring Digitally Subtracted Angiograms (DSAs). Furthermore, we propose a registration algorithm using the new CT phase that aligns arterial structures in two steps: (a) Initialization of one corresponding feature using vessel diameter information, (b) optimization on three rotational and one translational parameter to register vessel structures that are represented as centerline graphs. We form a space of good features by iteratively creating new graphs from projected centerline images and by restricting the correspondence search only on branching points (the vertices) of the vessel tree. This algorithm shows good convergence and proves to be robust against deformation changes, which is demonstrated through studies on one phantom and three patients. PMID- 17354974 TI - A new registration/visualization paradigm for CT-fluoroscopy guided RF liver ablation. AB - 2D-3D slice-to-volume registration for abdominal organs like liver is difficult due to the breathing motion and tissue deformation. The purpose of our approach is to ease CT-fluoroscopy (CT-fluoro) based needle insertion for the Radiofrequency Liver Ablation procedure using high resolution contrasted preoperative data. In this case, low signal-to-noise ratio, absence of contrast and additional presence of needle in CT-fluoro makes it difficult to guarantee the solution of any deformable slice-to-volume registration algorithm. In this paper, we first propose a method for creating a set of ground truth (GT) simulation data based on a non-linear deformation of the CT-fluoro volume obtained from real patients. Second, we split the CT-fluoro image and apply intensity based rigid and affine registration to each section. We then propose a novel solution, which consists of intuitive visualization sequences of optimal sub-volumes of preinterventional data based on the registration results. Experiments on synthetic and real patient data and direct feedback of two interventionalists validate our alternative approach. PMID- 17354975 TI - A new method for CT to fluoroscope registration based on unscented Kalman filter. AB - We propose a new method for CT to fluoroscope registration which is very robust and has a wide capture range. The method relies on the Unscented Kalman Filter to search for an optimal registration solution and on modern commodity graphics cards for fast generation of digitally reconstructed radiographs. We extensively test our method using three different anatomical data sets and compare it with an implementation of the commonly used simplex-based method. The experimental results firmly support that, under the same testing conditions, our proposed technique outperforms the simplex-based method in capture range while providing comparable accuracy and computation time. PMID- 17354976 TI - Automated 3D freehand ultrasound calibration with real-time accuracy control. AB - 3D ultrasound (US) is an emerging new imaging technology that appeals to more and more applications in intraoperative guidance of computer-assisted surgery. In a freehand US imaging system, US probe calibration is typically required to construct a 3D image of the patient's anatomy from a set of 2D US images. Most of the current calibration techniques concern primarily with the precision and accuracy. However, for computer-assisted surgeries that may require a calibration task inside the operating room (OR), many other important aspects have to be considered besides accuracy. In this paper, we propose a novel system for automated calibration that is optimized for the OR usage with real-time feedback and control of the calibration accuracy. We have also designed a novel N-wire phantom, with greatly reduced complexity to facilitate mass production without compromising the accuracy and robustness. PMID- 17354977 TI - Non-rigid registration of 3D multi-channel microscopy images of cell nuclei. AB - We present an intensity-based non-rigid registration approach for normalizing 3D multi-channel microscopy images of cell nuclei. A main problem with cell nuclei images is that the intensity structure of different nuclei differs very much, thus an intensity-based registration scheme cannot be used directly. Instead, we first perform a segmentation of the images, smooth them by a Gaussian filter, and then apply an intensity-based algorithm. To improve the convergence rate of the algorithm, we propose an adaptive step length optimization scheme and also employ a multi-resolution scheme. Our approach has been successfully applied using 2D cell-like synthetic images, 3D phantom images as well as 3D multichannel microscopy images representing different chromosome territories and gene regions (BACs). We also describe an extension of our approach which is applied for the registration of 3D+t (4D) image series of moving cell nuclei. PMID- 17354978 TI - Fast deformable registration of 3D-ultrasound data using a variational approach. AB - We present an intensity based deformable registration algorithm for 3D ultrasound data. The proposed method uses a variational approach and combines the characteristics of a multilevel algorithm and the properties of ultrasound data in order to provide a fast and accurate deformable registration method. In contrast to previously proposed approaches, we use no feature points and no interpolation technique, but compute a dense displacement field directly. We demonstrate that this approach, although it includes solving large PDE systems, reduces the computation time if implemented using efficient numerical techniques. The performance of the algorithm is tested on multiple 3D US images of the liver. Validation is performed by simulations, similarity comparisons between original and deformed images, visual inspection of the displacement fields and visual assessment of the deformed images by physicians. PMID- 17354979 TI - A log-Euclidean framework for statistics on diffeomorphisms. AB - In this article, we focus on the computation of statistics of invertible geometrical deformations (i.e., diffeomorphisms), based on the generalization to this type of data of the notion of principal logarithm. Remarkably, this logarithm is a simple 3D vector field, and is well-defined for diffeomorphisms close enough to the identity. This allows to perform vectorial statistics on diffeomorphisms, while preserving the invertibility constraint, contrary to Euclidean statistics on displacement fields. We also present here two efficient algorithms to compute logarithms of diffeomorphisms and exponentials of vector fields, whose accuracy is studied on synthetic data. Finally, we apply these tools to compute the mean of a set of diffeomorphisms, in the context of a registration experiment between an atlas an a database of 9 T1 MR images of the human brain. PMID- 17354980 TI - Nonrigid 3D brain registration using intensity/feature information. AB - The brain deforms non-rigidly during neurosurgery, preventing preoperatively acquired images from accurately depicting the intraoperative brain. If the deformed brain surface can be detected, biomechanical models can be applied to calculate the resulting volumetric deformation. The reliability of this volumetric calculation is dependent on the accuracy of the surface detection. This work presents a surface tracking algorithm which relies on Bayesian analysis to track cortical surface movement. The inputs to the model are 3D preoperative brain images and intraoperative stereo camera images. The addition of a camera calibration optimization term creates a more robust model, capable of tracking the cortical surface in the presence of camera calibration error. PMID- 17354981 TI - Are we 'following the money' too much? PMID- 17354982 TI - A GAO report on the costs of HHD: will it help or hurt the renal community? PMID- 17354983 TI - WHO reports counterfeit drugs are a global calamity. PMID- 17354984 TI - Advances and emerging opportunities in type 1 diabetes: a strategic plan. PMID- 17354985 TI - New heparin coating reduces thrombosis and fibrin sheath formation in HD catheters. PMID- 17354986 TI - Home dialysis: a fresh look at reimbursement methods. AB - Method selection, though applying only to the Medicare patient, still encompasses the majority of the dialysis patient population. Taking the time to run the numbers and to use both Methods to the advantage of your program might well have a significant impact on the profitability of a home dialysis program. PMID- 17354987 TI - HHD: a better way to do dialysis. PMID- 17354988 TI - DaVita at home: an overview. PMID- 17354989 TI - Going the distance. . .with renal disease. PMID- 17354990 TI - Tax saving ideas for physician practices. AB - As a top-earning physician, you spend 40 percent to 50 percent of your working hours laboring for the IRS and your state. That is a lot of time with patients, at the practice, in the hospital and on call. This article offers five ways to potentially save taxes on your income and will possibly motivate you to investigate these planning concepts throughout the year. PMID- 17354991 TI - What is wrong with intelligent design? AB - This article reviews two standard criticisms of creationism/intelligent design (ID)): it is unfalsifiable, and it is refuted by the many imperfect adaptations found in nature. Problems with both criticisms are discussed. A conception of testability is described that avoids the defects in Karl Popper's falsifiability criterion. Although ID comes in multiple forms, which call for different criticisms, it emerges that ID fails to constitute a serious alternative to evolutionary theory. PMID- 17354992 TI - Costs and benefits of within-group spatial position: a feeding competition model. AB - An animal's within-group spatial position has several important fitness consequences. Risk of predation, time spent engaging in antipredatory behavior and feeding competition can all vary with respect to spatial position. Previous research has found evidence that feeding rates are higher at the group edge in many species, but these studies have not represented the entire breadth of dietary diversity and ecological situations faced by many animals. In particular the presence of concentrated, defendable food patches can lead to increased feeding rates by dominants in the center of the group that are able to monopolize or defend these areas. To fully understand the tradeoffs of within-group spatial position in relation to a variety of factors, it is important to be able to predict where individuals should preferably position themselves in relation to feeding rates and food competition. A qualitative model is presented here to predict how food depletion time, abundance of food patches within a group, and the presence of prior knowledge of feeding sites affect the payoffs of different within-group spatial positions for dominant and subordinate animals. In general, when feeding on small abundant food items, individuals at the front edge of the group should have higher foraging success. When feeding on slowly depleted, rare food items, dominants will often have the highest feeding rates in the center of the group. Between these two extreme points of a continuum, an individual's optimal spatial position is predicted to be influenced by an additional combination of factors, such as group size, group spread, satiation rates, and the presence of producer-scrounger tactics. PMID- 17354993 TI - House calls: activism is all in a day's work. PMID- 17354994 TI - Physician executives and the political process. PMID- 17354995 TI - How to influence state legislatures and regulatory agencies. PMID- 17354996 TI - Using strategy: the evolution of a medical practice. PMID- 17354997 TI - Going solo in a group--part 2. PMID- 17354998 TI - Standing out in a higly competitive job market. PMID- 17354999 TI - Building, maintaining and recovering trust: a core leadership competency. PMID- 17355000 TI - The physician condition: the age of economic medicine. AB - A university professor believes the combination of Generation X physicians, who assert different expectations about work and home-life compared to Baby Boomer physicians, and the influx of female physicians over the past three decades, has profound implications on the structure of the health care industry. PMID- 17355001 TI - Raising the bar of safety for your medical staff. PMID- 17355002 TI - Professional review committee improves the peer review process. PMID- 17355003 TI - Coming soon: comparison shopping on product, price and performance. PMID- 17355004 TI - The power of professionalism: should it be used as a political weapon? PMID- 17355005 TI - Genetic testing in the workplace. PMID- 17355006 TI - Understanding your dimensions of agreement. PMID- 17355007 TI - Carrying the load together. PMID- 17355008 TI - New man at Portsmouth. Interview by James Verrinder. PMID- 17355009 TI - Redevelopment on massive scale. PMID- 17355010 TI - Essential tasks must be programmed effectively. AB - Few would argue that maintenance is not a problem. Practices do not eliminate problems, but only proper practice makes perfect maintenance. To master management of building services maintenance, there is no better teacher than experience. You must plan your maintenance system thoughtfully and try it out together with your professional knowledge. The system outlined in this article gives a systematic procedure in setting up a workable maintenance plan. The tedious management work and the inconvenience caused to a busy or new maintenance department will probably mean greater pressure of work for the maintenance engineer in the first year, but thereafter the pressure will be less than before and benefits of an organised system of maintenance will repay the effort of introducing it. It is essential that the paperwork be as simple as possible and very flexible in operation so that amendments can be made easily. Preparation of paperwork is by no means easy. It is highly likely that your schedules and programmes will have to be rewritten two or three times before arriving at the optimum plan. My management lecturer once told me: "Without a plan and a programme, you don't know whether you have done all the things that you need to do, and you will end up with many problems." Good planning gives you confidence, but take my advice--do not over plan. Too much paperwork can be just as bad if not worse than too little paper. Information will be of no use if it cannot be read, digested and used in practice. PMID- 17355011 TI - Agenda set by NHS operating framework. PMID- 17355012 TI - Lift safety must ascend to highest levels. PMID- 17355013 TI - Letter writing could be dangerous. 1950. PMID- 17355014 TI - Plaster cast for new role in hospitals. PMID- 17355015 TI - Re-boot recommended for IT initiative. PMID- 17355016 TI - Speech recognition systems excel. PMID- 17355017 TI - Cervical disc arthroplasty compared with allograft fusion. PMID- 17355018 TI - Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial. AB - OBJECT: The authors report the results of a prospective randomized multicenter study in which the results of cervical disc arthroplasty were compared with anterior cervical discectomy and fusion (ACDF) in patients treated for symptomatic single-level cervical degenerative disc disease (DDD). METHODS: Five hundred forty-one patients with single-level cervical DDD and radiculopathy were enrolled at 32 sites and randomly assigned to one of two treatment groups: 276 patients in the investigational group underwent anterior cervical discectomy and decompression and arthroplasty with the PRESTIGE ST Cervical Disc System (Medtronic Sofamor Danek); 265 patients in the control group underwent decompressive ACDF. Eighty percent of the arthroplasty-treated patients (223 of 276) and 75% of the control patients (198 of 265) completed clinical and radiographic follow-up examinations at routine intervals for 2 years after surgery. Analysis of all currently available postoperative 12- and 24-month data indicated a two-point greater improvement in the neck disability index score in the investigational group than the control group. The arthroplasty group also had a statistically significant higher rate of neurological success (p = 0.005) as well as a lower rate of secondary revision surgeries (p = 0.0277) and supplemental fixation (p = 0.0031). The mean improvement in the 36-Item Short Form Health Survey Physical Component Summary scores was greater in the investigational group at 12 and 24 months, as was relief of neck pain. The patients in the investigational group returned to work 16 days sooner than those in the control group, and the rate of adjacent-segment reoperation was significantly lower in the investigational group as well (p = 0.0492, log-rank test). The cervical disc implant maintained segmental sagittal angular motion averaging more than 7 degrees. In the investigational group, there were no cases of implant failure or migration. CONCLUSIONS: The PRESTIGE ST Cervical Disc System maintained physiological segmental motion at 24 months after implantation and was associated with improved neurological success, improved clinical outcomes, and a reduced rate of secondary surgeries compared with ACDF. PMID- 17355019 TI - Tethered cord due to spina bifida occulta presenting in adulthood: a tricenter review of 61 patients. AB - OBJECT: Children with spina bifida occulta require early surgery to prevent neurological deficits. The treatment of patients with a congenitally tethered cord who present in adulthood remains controversial. METHODS: The authors studied the medical records of 61 adult patients who underwent surgical untethering for spina bifida occulta at three institutions between 1994 and 2003. Patients who had undergone prior myelomeningocele repair or tethered cord release surgery were excluded. The most common intraoperative findings were lipomyelomeningocele (41%) and a tight terminal filum (36%). The follow-up duration ranged from 10.8 to 149.5 months. Of the 34 patients with back pain, status improved in 65%, worsened in 3%, remained unchanged in 18%, and improved and later recurred in 15%. Lower extremity pain improved in 16 patients (53%), remained unchanged in 23%, improved and then recurred in 17%, and worsened in 7%. Lower-extremity weakness improved in 47%, remained unchanged in 47%, and improved and then recurred in 5%. Finally, of the 17 patients with lower-extremity sensory changes, status improved in 35%, remained unchanged in 35%, and the information on five patients was unavailable. Surgical complications included three wound infections, one cerebrospinal fluid leak, and two pseudomeningoceles requiring surgical revision. One patient developed acute respiratory distress syndrome and sepsis postoperatively and died several days later. CONCLUSIONS: Adult-age presentation of a congenital tethered cord is unusual. Despite a slight increase in postoperative neurological injury in adults, surgery has relatively low risk and offers good potential for neurological improvement or stabilization. As they do in children, the authors recommend early surgery in adults with this disorder. The decision to undertake surgery, however, should be modulated by other factors such as a patient's general medical condition and risk posed by anesthesia. PMID- 17355020 TI - Surgical outcomes in adult patients with syringomyelia associated with Chiari malformation type I: the relationship between scoliosis and neurological findings. AB - OBJECT: The clinical characteristics of pediatric scoliosis associated with syringomyelia have been reported in previous studies, but scoliosis associated with syringomyelia in adults is rarely treated, and there is a paucity of detailed studies. In the present study of adult syringomyelia associated with Chiari malformation Type I, the authors investigated the relationships among the syrinx, scoliosis, and neurological data. METHODS: The population was composed of 27 patients (> or = 20 years of age) who underwent foramen magnum decompression for the treatment of syringomyelia. The patients were divided into two groups: those with scoliosis of 10 degrees or more (Group A) and those without scoliosis (Group B). The authors assessed the length of the syrinx, duration of morbidity, and clinical status before and after surgery based on the Japanese Orthopaedic Association (JOA) Scale. There were 15 cases in Group A and 12 in Group B. The mean length of the syrinx was 12.8 vertebral bodies (VBs) in Group A and 7.2 VBs in Group B. The mean duration of morbidity was 14.2 years in Group A and 6.8 years in Group B. The mean preoperative JOA score was 10.1 in Group A and 14.4 in Group B, whereas the mean postoperative JOA scores were 11.9 and 15.8, respectively. There were significant differences between Groups A and B in length of the syrinx, duration of morbidity, and pre- and postoperative JOA scores. CONCLUSIONS: In patients with syringomyelia and scoliosis the syringes spanned a greater number of VBs, the duration of morbidity was greater, neurological dysfunction was more severe, and surgical results were poorer. Scoliosis could be a predicting factor of the prognosis in patients with syringomyelia and Chiari malformation Type I. PMID- 17355021 TI - Medical management of Pott disease in the thoracic and lumbar spine: a prospective clinical study. AB - OBJECT: The aim of this study was to evaluate conservative medical management of 44 patients with Pott disease. The prognostic significance of various clinical, radiological, and long-term follow-up findings in these patients was also evaluated. METHODS: Between January 1990 and January 2005 data were collected prospectively at the authors' clinic in 44 patients with Pott disease in the thoracic or lumbar spine. These patients had no major neurological deficits or severe spinal deformities. The study population consisted of 21 male (48%) and 23 female (52%) patients, with a mean age of 42.1 years (range 10-70 years). The most common region of Pott disease was the thoracolumbar junction (18 cases; 41%), followed by the thoracic (16 cases; 36%) and lumbar (10 cases; 23%) regions. All patients presented with abscesses. With the exception of two cases, all had kyphotic angles smaller than 30 degrees. At presentation, 20 patients had neurological signs of spinal cord compression during clinical examination. Both clinical and biopsy findings were used in all cases for diagnosis. A diagnosis was confirmed by a positive biopsy specimen culture in 19 (43.2%) of 44 cases, and histopathological findings were compatible with the results of these cultures in all cases. All patients were treated with antituberculous chemotherapy, and the diseases in only two (4.5%) was resistant to the regimen. An independent observer assessed the clinical and imaging findings after a mean follow-up duration of 40 months. Forty-two (95.4%) of the 44 patients were successfully treated with conservative medical management and attained acceptable spinal deformity angles, and none of these patients had any residual instability, radiculopathy, or neurological compromise. Only 4.5% of the patients experienced residual spine deformity (as much as a 30 degrees kyphotic angle), which was clinically obvious but biomechanically stable. CONCLUSIONS: Patients with Pott disease in the lumbar or thoracic region, without neurological deficits or kyphosis, can be treated conservatively in the vast majority of cases. Indications for surgery need to be redefined given these new data. PMID- 17355022 TI - Split-spinous process laminotomy and discectomy for degenerative lumbar spinal stenosis: a preliminary report. AB - OBJECT: The authors evaluated a new minimally invasive spinal surgery technique to correct degenerative lumbar spinal stenosis involving a split-spinous process laminotomy and discectomy (also known as the "Marmot operation"). METHODS: This prospective study randomized 70 patients with lumbar stenosis to undergo either a Marmot operation (40 patients), or a conventional laminectomy (30 patients), with or without discectomy. Spinal anteroposterior diameter, cross-sectional area, lateral recess distance, spinal stability, postoperative back pain, functional outcomes, and muscular trauma were evaluated. The follow up ranged from 10 to 18 months, with a mean of 15.1 months for the Marmot operation group and 14.8 months for the conventional laminectomy group. Compared with patients in the conventional laminectomy group, patients who received a Marmot operation had a shorter mean postoperative duration until ambulation without assistance, a reduced mean duration of hospital stay, a lower mean creatine phosphokinase muscular-type isoenzyme level, a lower visual analog scale score for back pain at 1-year follow up, and a better recovery rate. These patients also had a longer mean duration of operative time and a greater mean blood loss compared with the conventional group. Satisfactory neurological decompression and symptom relief were achieved in 93% of these patients. Most of the patients (66%) in this group needed discectomy for decompression. The postoperative mean lateral recess width, spinal anteroposterior diameter, and cross-sectional area were all significantly increased. There was no evidence of spinal instability in any patient. One patient with insufficient lateral recess decompression and recurrent disc herniation needed additional conventional laminectomy and discectomy, and one patient with mild superficial wound infection was successfully treated with antibiotics and frequent dressing changes. CONCLUSIONS: A Marmot operation may provide effective spinal decompression. Although this method requires more operative time than a conventional method, it may involve only minimal muscular trauma, spinal stability maintenance, and early mobilization; shorten the duration of hospital stay; reduce postoperative back pain; and provide satisfactory neurological and functional outcomes. PMID- 17355023 TI - Cyclooxygenase-2 expression in ependymoma of the spinal cord. AB - OBJECT: Cyclooxygenase-2 (COX-2), also known as prostaglandin endoperoxide synthase, has been reported to play an important role in the tumorigenicity of many types of tumors. The expression of COX-2 in spinal ependymomas, however, has not been studied. The authors evaluated COX-2 expression in ependymoma of the spinal cord. METHODS: Sixteen ependymoma samples obtained in patients undergoing surgery between 1995 and 2004 were utilized for immunohistochemical studies to evaluate COX-2 and vascular endothelial growth factor (VEGF) expression. Intratumoral microvessels were also stained immunohistochemically using anti human von Willebrand factor antibody and were quantified to determine the microvessel density (MVD). The clinical features were reviewed and recorded and the association with COX-2 expression was assessed. Seven (43.8%) of the 16 ependymoma specimens expressed COX-2. All three of the myxopapillary-type ependymomas exhibited COX-2-positive staining. Excluding the three myxopapillary type cases, COX-2 expression was identified in four (30.8%) of 13 cellular-type ependymomas. The COX-2-positive samples exhibited a significant increase in VEGF positive staining cells and MVD compared with COX-2-negative samples. The clinical features were not associated with COX-2 expression. CONCLUSIONS: The results of the present study indicate that COX-2 expression may promote angiogenesis through VEGF expression in ependymomas of the spinal cord. It is suggested that the use of selective COX-2 inhibitors may provide a new therapeutic strategy for spinal cord ependymomas due to their inhibition of the COX-2-mediated angiogenesis. PMID- 17355024 TI - Working area, safety zones, and angles of approach for posterior C-1 lateral mass screw placement: a quantitative anatomical and morphometric evaluation. AB - OBJECT: The authors measured relevant quantitative anatomical parameters to define safety zones for the placement of C-1 posterior screws. METHODS: Nineteen linear, two angular, and four surface parameters of 20 dried atlantal specimens were evaluated. The Optotrak 3020 system was used to define the working area. Ideal angles for screw positioning were measured using digital radiographs and a free image-processing program. Six silicone-injected cadaveric heads were dissected bilaterally to study related neurovascular anatomy. The depth (range 5.2-9.4 mm, mean 7.2 +/- 1.1 mm) and width (range 5.2-8.1 mm, mean 6.5 +/- 0.9 mm) of the transverse foramen varied considerably among specimens. The mean posterior working area was 43.3 mm2. All specimens accommodated 3.5-mm-diameter screws, and 93% accepted 4-mm-diameter screws. In 10 specimens (50%), partial removal of the posterior arch was necessary to accommodate a 4-mm screw. The mean maximum angle of medialization was 16.7 +/- 1.3 degrees; the mean maximum superior angulation was 21.7 +/- 4.7 degrees. CONCLUSIONS: The anatomical configuration of the atlas and vertebral artery (VA) varied considerably among the cadaveric specimens. The heights of the C-1 pedicle, posterior arch, and posterior lamina determine the posterior working area available for screw placement. The inferior insertion of the posterior arch may have to be drilled to increase this working area, but doing so risks injury to the VA. A dense venous plexus with multiple anastomoses may cover the screw entry site, potentially obscuring the operative view and increasing the risk of hemorrhage. PMID- 17355026 TI - Augmentation of an anterior lumbar interbody fusion with an anterior plate or pedicle screw fixation: a comparative biomechanical in vitro study. AB - OBJECT: Posterior pedicle screw (PS) instrumentation is often used to augment anterior lumbar interbody fusion (ALIF) but at the cost of an increase in the morbidity rate due to the second approach and screw placement. If anterior plates were found to be biomechanically equivalent to PS fixation (PSF) after ALIF, then this second approach could be avoided without decreasing vertebral stability. METHODS: Eight cadaveric L5-S1 spinal segments were tested under four conditions: intact, following anterior discectomy and interbody spacer placement, after placement of an anterior plate, and following PSF. The elastic zone and stiffness were calculated for axial compression, flexion/extension, lateral bending, and torsion. Neither anterior plate stabilization nor PSF showed significant intergroup differences in stiffness or the elastic zone. Both exhibited greater stiffness in flexion than the intact specimens (p < 0.001). Pedicle screw fixation was associated with a decreased elastic zone in lateral bending compared with the intact specimen (p < 0.04). CONCLUSIONS: Anterior plate fixation is biomechanically similar to PSF following ALIF. Surgeons may wish to use anterior plates in place of PSs to avoid the need for a posterior procedure. This may lead to a decrease in operative morbidity and improved overall outcomes. PMID- 17355025 TI - Contusion, dislocation, and distraction: primary hemorrhage and membrane permeability in distinct mechanisms of spinal cord injury. AB - OBJECT: In experimental models of spinal cord injury (SCI) researchers have typically focused on contusion and transection injuries. Clinically, however, other injury mechanisms such as fracture-dislocation and distraction also frequently occur. The objective of the present study was to compare the primary damage in three clinically relevant animal models of SCI. METHODS: Contusion, fracture-dislocation, and flexion-distraction animal models of SCI were developed. To visualize traumatic increases in cellular membrane permeability, fluorescein-dextran was infused into the cerebrospinal fluid prior to injury. High-speed injuries (approaching 100 cm/second) were produced in the cervical spine of deeply anesthetized Sprague-Dawley rats (28 SCI and eight sham treated) with a novel multimechanism SCI test system. The animals were killed immediately thereafter so that the authors could characterize the primary injury in the gray and white matter. Sections stained with H & E showed that contusion and dislocation injuries resulted in similar central damage to the gray matter vasculature whereas no overt hemorrhage was detected following distraction. Contusion resulted in membrane disruption of neuronal somata and axons localized within 1 mm of the lesion epicenter. In contrast, membrane compromise in the dislocation and distraction models was observed to extend rostrally up to 5 mm, particularly in the ventral and lateral white matter tracts. CONCLUSIONS: Given the pivotal nature of hemorrhagic necrosis and plasma membrane compromise in the initiation of downstream SCI pathomechanisms, the aforementioned differences suggest the presence of mechanism-specific injury regions, which may alter future clinical treatment paradigms. PMID- 17355027 TI - Return of normal urological and neurological function after revision surgery for spondyloptosis. Case report. AB - The authors report on the return of neurological and urological function in an adolescent after revision surgery for spondyloptosis 5 years after the index procedure for high-grade spondylolisthesis. This 16-year-old girl with Grade 3 spondylolisthesis was initially treated with a posterolateral reduction and fusion. Following surgery, cauda equina syndrome symptoms developed and did not resolve despite subsequent surgical decompression. Five years later, because of worsening radicular pain, an inability to walk for significant distances, and no resolution of persistent bladder dysfunction, the patient presented with spondyloptosis. Posterior decompression, sacral dome osteotomy, and posterior reduction were performed and followed 3 days later with the placement of an anterior fibula autograft. Her bladder function recovered within 6 months, and at the 18-month follow up the patient reported a normal ability to ambulate. PMID- 17355028 TI - Fatal cerebral and cerebellar hemorrhagic infarction after thoracoscopic microdiscectomy. Case report. AB - The authors present a rare case of fatal cerebral and cerebellar hemorrhagic infarction following an uneventful thoracoscopic microdiscectomy. They hypothesize that this complication was associated with cortical venous thrombosis secondary to intracranial hypotension, which was caused by an unnoticed leak of cerebrospinal fluid (CSF) into the thoracic cavity. Cortical venous thrombosis and intrathoracic CSF were confirmed at autopsy. The former disorder is the most severe manifestation of the pathophysiological mechanism occurring to a lesser degree in patients affected by mild intracranial hypotension, and occurs more frequently in these patients. Intracranial hypotension (of an orthostatic nature or not) must be considered in the differential diagnosis of every patient who complains of headaches after thoracoscopic or open transthoracic microdiscectomy. PMID- 17355029 TI - Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report. AB - Vincristine has a high neurotoxicity level. If given intrathecally by accident, it can cause ascending radiculomyeloencephalopathy, which is almost always fatal. The authors report a rare case in which vincristine was accidentally injected intrathecally into a 32-year-old man. The patient, who had Burkitt lymphoma, was neurologically intact, and it is likely that his survival was made possible due to aggressive neurosurgical therapy. After immediate cerebrospinal fluid (CSF) aspiration, external ventricular and lumbar drains were placed for CSF irrigation, which was continued for 6 days. This CSF irrigation was combined with 1) the intrathecal administration of fresh-frozen plasma to bind the vincristine and 2) an intravenous antineurotoxic therapy involving pyridoxine, folic acid, and glutamic acid. The patient's first sensorimotor deficits occurred after 2 days, led to an incomplete sensorimotor dysfunction below T-9 within the next 17 days, but progressed no further. Supported by the scarce data culled from the reviewed literature, the authors hypothesize that prolonged CSF irrigation combined with antineurotoxic therapy contributed to the patient's satisfactory outcome. In conclusion, accidental intrathecal vincristine injection requires emergency and adequate neurosurgical therapy. PMID- 17355030 TI - Open kyphoplasty for management of metastatic and severe osteoporotic spinal fracture. Technical note. AB - OBJECT: Elderly patients in poor general health frequently suffer vertebral body (VB) fractures due to osteoporosis or vertebral metastatic lesions. Kyphoplasty and vertebroplasty have become the standard treatment for these types of fractures. In certain conditions that cause local kyphosis, such as spinal cord compression due to a metastatic epidural tumor or the shortening of the spinal canal secondary to vertebral compression, the surgical treatment should provide decompression and stabilization during a short intervention. In this study the authors evaluated a surgical technique that frequently combines a same-session surgical decompression, such as a laminectomy, and posterior instrumentation assisted stabilization during the same open intervention in which the VB is stabilized by kyphoplasty. METHODS: During an 18-month period, the authors treated 18 patients with VB fractures according to this protocol: 14 patients with vertebral metastatic lesions and four with osteoporosis. The patients' mean age was 60 years. All suffered severe pain preoperatively (mean visual analog scale [VAS] score of 7). Fourteen of the 18 patients suffered a neurological deficit. Twenty-three vertebral levels were treated; in 15 patients it was necessary to place posterior instrumentation. The mean duration of the intervention was 90 minutes. Pain in all patients improved 3 days after the intervention, and the mean VAS score decreased to 2. Patients with a neurological dysfunction improved. The mean quantity of injected cement for the kyphoplasty procedure was 7 ml. The mean duration of hospitalization was 7 days. Neuroimaging revealed cement leaks in two cases: one into the disc interspace and one anteriorly into the fractured part of the vertebra. After the intervention, most patients with metastatic lesions underwent radiotherapy. No procedure-related complications occurred. CONCLUSIONS: This procedure allows decompression of the spinal cord, consolidation of the VB and thus a stabilization of the vertebral column, and may provide an alternative treatment to invasive VB excision in patients in poor general health. PMID- 17355031 TI - The Simon effect and handedness: evidence for a dominant-hand attentional bias in spatial coding. AB - In two experiments, the relation between handedness and the size of the Simon effect in each visual hemifield was investigated. Experiment 1 showed that the Simon effect was larger in the right visual hemifield in right-handers and in the left visual hemifield in left-handers, whereas ambidextrous individuals showed a symmetric Simon effect. In Experiment 2, participants performed the same Simon task as in Experiment 1, but with their hands crossed. The right- and left-handed groups showed a reversed pattern of results with respect to Experiment 1. We explained this phenomenon as a part of a more general account in which perception and action are embedded in a perception-for-action system. In this system, an attentional bias originating from the field of operation of the dominant hand would be at the basis of the relationship between the asymmetry of the Simon effect and handedness. PMID- 17355032 TI - Manual exploration and the perception of slipperiness. AB - In this article, we report on two experiments that examined the haptic perception of slipperiness. The first experiment aimed to determine whether the type of finger motion across a surface influenced the ability to accurately judge the frictional coefficient (or slipperiness) of that surface. Results showed that when using static contact, participants were not as good at distinguishing between various surfaces, compared with when their finger moved across the surface. This raises the issue of how humans are able to generate the appropriate forces in response to friction during grasping (which involves static finger contact). In a second study, participants lifted objects with surfaces of varying coefficients of friction. The participants were able to accurately perceive the slipperiness of the surfaces that were lifted; however, the grasping forces were not scaled appropriately for the friction. That is, there was a dissociation between haptic perception and motor output. PMID- 17355033 TI - A stereo advantage in generalizing over changes in viewpoint on object recognition tasks. AB - In four experiments, we examined whether generalization to unfamiliar views was better under stereo viewing or under nonstereo viewing across different tasks and stimuli. In the first three experiments, we used a sequential matching task in which observers matched the identities of shaded tube-like objects. Across Experiments 1-3, we manipulated the presentation method of the nonstereo stimuli (having observers wear an eye patch vs. showing observers the same screen image) and the magnitude of the viewpoint change (30 degrees vs. 38 degrees). In Experiment 4, observers identified "easy" and "hard" rotating wire-frame objects at the individual level under stereo and nonstereo viewing conditions. We found a stereo advantage for generalizing to unfamiliar views in all the experiments. However, in these experiments, performance remained view dependent even under stereo viewing. These results strongly argue against strictly 2-D image-based models of object recognition, at least for the stimuli and recognition tasks used, and suggest that observers used representations that contained view specific local depth information. PMID- 17355034 TI - Bimanual curvature discrimination of hand-sized surfaces placed at different positions. AB - This study explores bimanual curvature discrimination of cylindrically curved, hand-sized surfaces. The setup was designed so that the postures of the observers' left and right arms and hands were thesame as if the observers were holding a large object in their hands. We measured psychometric curves for observers who used active, dynamic touch; these curvatures ranged from 1.18 to 4.05/m. Bimanual discrimination thresholds were found to be between 0.26 and 0.38/m on average; they were in the same range as unimanual thresholds reported in previous studies. Variation of (1) the horizontal distance between the stimuli or (2) the position of the setup had no effect on thresholds. In addition, we found that a number of observers showed discrimination biases in which they judged two physically different curvatures to be equal. Biases were of the same order of magnitude as the thresholds and could be either positive or negative. These biases can possibly be explained by small differences in left and right arm movements, an explanation that is supported by the position dependence of biases for individual observers. PMID- 17355035 TI - The intensity-difference limen for 6.5 kHz: an even more severe departure from Weber's law. AB - Intensity-difference limens (DLs) were obtained for tones of 6.5 kHz over levels of 30-90 dB SPL. The tones had Gaussian-shaped envelopes whose duration was expressed as equivalent rectangular duration D, that of a rectangle enclosing the same area as the envelope. D ranged from 0.314 to 30 msec. DL behaviors such as the "severe departure from Weber's law," the "midlevel hump," or the "midduration hump"--that is, a rise in the DL over a range of short durations--were identified using trend analysis. The DL versus level followed a "severe departure" that increased as duration dropped to D approximately 1-2 msec. That midlevel hump then fell with further shortening of the tone pip, producing a mid-duration hump. Materials for this article may be accessed through the Psychonomic Society's Norms, Stimuli, and Data archive, at www.psychonomic.org/archive. PMID- 17355036 TI - Visual onset expands subjective time. AB - We report a distortion of subjective time perception in which the duration of a first interval is perceived to be longer than the succeeding interval of the same duration. The amount of time expansion depends on the onset type defining the first interval. When a stimulus appears abruptly, its duration is perceived to be longer than when it appears following a stationary array. The difference in the processing time for the stimulus onset and motion onset, measured as reaction times, agrees with the difference in time expansion. Our results suggest that initial transient responses for a visual onset serve as a temporal marker for time estimation, and a systematic change in the processing time for onsets affects perceived time. PMID- 17355037 TI - Binocular shape constancy from novel views: the role of a priori constraints. AB - We tested shape constancy from novel views in the case of binocular viewing, using a variety of stimuli, including polyhedra, polygonal lines, and points in 3 D. The results of the psychophysical experiments show that constraints such as planarity of surface contours and symmetry are critical for reliable shape constancy. These results are consistent with the results obtained in our previous psychophysical experiments on shape constancy from novel views in the presence of a kinetic depth effect (Pizlo & Stevenson, 1999). On the basis of these results, we developed a new model of binocular shape reconstruction. The model is based on the assumption that binocular reconstruction is a difficult inverse problem, whose solution requires imposing a priori constraints on the family of possible interpretations. In the model, binocular disparity is used to correct monocularly reconstructed shape. The new model was tested on the same shapes as those used in the psychophysical experiments. The reconstructions produced by this model are substantially more reliable than the reconstructions produced by models that do not use constraints. Interestingly, monocular (but not binocular) reconstructions produced by this model correlate well with both monocular and binocular performance of human subjects. This fact suggests that binocular and monocular reconstructions of shapes in the human visual system involve similar mechanisms based on monocular shape constraints. PMID- 17355038 TI - Crossmodal temporal discrimination: assessing the predictions of a general pacemaker-counter model. AB - In this study, an extended pacemaker-counter model was applied to crossmodal temporal discrimination. In three experiments, subjects discriminated between the durations of a constant standard stimulus and a variable comparison stimulus. In congruent trials, both stimuli were presented in the same sensory modality (i.e., both visual or both auditory), whereas in incongruent trials, each stimulus was presented in a different modality. The model accounts for the finding that temporal discrimination depends on the presentation order of the sensory modalities. Nevertheless, the model fails to explain why temporal discrimination was much better with congruent than with incongruent trials. The discussion considers possibilities to accommodate the model to this and other shortcomings. PMID- 17355039 TI - Attentional set for axis of symmetry in symmetry-defined visual search. AB - Olivers and van der Helm (1998) showed that symmetry-defined visual search (for both symmetry and asymmetry) requires selective spatial attention. We hypothesize that an attentional set for the orientation of a symmetry axis also is involved in symmetry-defined visual search. We conducted three symmetry-defined visual search experiments with manipulations of the axis of symmetry orientations, and performance was better when the axis orientations within the search array were uniform, rather than a mixture of two orientations, and the attentional set for the axis orientation could be kept. In addition, search performance when the target was defined by the presence of symmetry was equivalent to that when the target was defined by a difference of symmetry axis orientation. These results suggest that attentional set for axis orientation plays a fundamental role in symmetry-defined visual search. PMID- 17355040 TI - The return of object-based attention: selection of multiple-region objects. AB - Objects can control the focus of attention, allowing features on the same object to be selected more easily than features on different objects. In the present experiments, we investigated the perceptual processes that contribute to such object-based attentional effects. Previous research has demonstrated that object based effects occur for single-region objects but not for multiple-region objects under some conditions (Experiment 1, Watson & Kramer, 1999). Such results are surprising, because most objects in natural scenes are composed of multiple regions. Previous findings could therefore limit the usefulness of an object based selection mechanism. We explored the generality of these single-region selection results by manipulating the extent to which different (i.e., multiple) regions of a single object perceptually grouped together. Object-based attentional effects were attenuated when multiple regions did not group into a single perceptual object (Experiment 1). However, when multiple regions grouped together based on (1) edge continuation (Experiments 2 and 3) or (2) part and occlusion cues (Experiment 4), we observed object-based effects. Our results suggest that object-based attention is a robust process that can select multiple region objects, provided the regions of such objects cohere on the basis of perceptual grouping cues. PMID- 17355041 TI - Stimulus modality interacts with category structure in perceptual category learning. AB - Two experiments were conducted that examined information integration and rule based category learning, using stimuli that contained auditory and visual information. The results suggest that it is easier to perceptually integrate information within these sensory modalities than across modalities. Conversely, it is easier to perform a disjunctive rule-based task when information comes from different sensory modalities, rather than from the same modality. Quantitative model-based analyses suggested that the information integration deficit for across-modality stimulus dimensions was due to an increase in the use of hypothesis-testing strategies to solve the task and to an increase in random responding. The modeling also suggested that the across-modality advantage for disjunctive, rule-based category learning was due to a greater reliance on disjunctive hypothesis-testing strategies, as opposed to unidimensional hypothesis-testing strategies and random responding. PMID- 17355042 TI - Multisensory synesthetic interactions in the speeded classification of visual size. AB - In the present study, we attempted to demonstrate a synesthetic relationship between auditory frequency and visual size. In Experiment 1, participants performed a speeded visual size discrimination task in which they had to judge whether a variable-sized disk was bigger or smaller than a standard reference disk. A task-irrelevant sound that was either synesthetically congruent with the relative size of the disk (e.g., a low-frequency sound presented with a bigger disk) or synesthetically incongruent with it (e.g., a low-frequency sound presented with a smaller disk) was sometimes presented together with the variable disk. Reaction times were shorter in the synesthetically congruent condition than in the incongruent condition. Verbal labeling and semantic mediation interpretations of this interaction were explored in Experiment 2, in which high- and low-frequency sounds were presented in separate blocks of trials, and in Experiment 3, in which the tones were replaced by the spoken words "high" and "low." Response priming/bias explanations were ruled out in Experiment 4, in which a synesthetic congruency effect was still reported even when participants made same-versus-different discrimination responses regarding the relative sizes of the two disks. Taken together, these results provide the first empirical demonstration that the relative frequency of an irrelevant sound can influence the speed with which participants judge the size of visual stimuli when the sound varies on a trial-by-trial basis along a synesthetically compatible dimension. The possible cognitive bases for this synesthetic association are also discussed. PMID- 17355043 TI - Contextual cuing by global features. AB - In visual search tasks, attention can be guided to a target item--appearing amidst distractors--on the basis of simple features (e.g., finding the red letter among green). Chun and Jiang's (1998) contextual cuing effect shows that reaction times (RTs) are also speeded if the spatial configuration of items in a scene is repeated over time. In the present studies, we ask whether global properties of the scene can speed search (e.g., if the display is mostly red, then the target is at location X). In Experiment 1A, the overall background color of the display predicted the target location, and the predictive color could appear 0, 400, or 800 msec in advance of the search array. Mean RTs were faster in predictive than in nonpredictive conditions. However, there was little improvement in search slopes. The global color cue did not improve search efficiency. Experiments 1B-1F replicated this effect using different predictive properties (e.g., background orientation-texture and stimulus color). The results showed a strong RT effect of predictive background, but (at best) only a weak improvement in search efficiency. A strong improvement in efficiency was found, however, when the informative background was presented 1,500 msec prior to the onset of the search stimuli and when observers were given explicit instructions to use the cue (Experiment 2). PMID- 17355044 TI - Biases in the perceived timing of perisaccadic perceptual and motor events. AB - Subjects typically experience the temporal interval immediately following a saccade as longer than a comparable control interval. One explanation of this effect is that the brain antedates the perceptual onset of a saccade target to around the time of saccade initiation. This could explain the apparent continuity of visual perception across eye movements. This antedating account was tested in three experiments in which subjects made saccades of differing extents and then judged either the duration or the temporal order of key events. Postsaccadic stimuli underwent subjective temporal lengthening and had early perceived onsets. A temporally advanced awareness of saccade completion was also found, independently of antedating effects. These results provide convergent evidence supporting antedating and differentiating it from other temporal biases. PMID- 17355045 TI - On the causes of compensation for coarticulation: evidence for phonological mediation. AB - This study examined whether compensation for coarticulation in fricative-vowel syllables is phonologically mediated or a consequence of auditory processes. Smits (2001a) had shown that compensation occurs for anticipatory lip rounding in a fricative caused by a following rounded vowel in Dutch. In a first experiment, the possibility that compensation is due to general auditory processing was investigated using nonspeech sounds. These did not cause context effects akin to compensation for coarticulation, although nonspeech sounds influenced speech sound identification in an integrative fashion. In a second experiment, a possible phonological basis for compensation for coarticulation was assessed by using audiovisual speech. Visual displays, which induced the perception of a rounded vowel, also influenced compensation for anticipatory lip rounding in the fricative. These results indicate that compensation for anticipatory lip rounding in fricative-vowel syllables is phonologically mediated. This result is discussed in the light of other compensation-for-coarticulation findings and general theories of speech perception. PMID- 17355046 TI - Modeling soft-tissue deformation prior to cutting for surgical simulation: finite element analysis and study of cutting parameters. AB - This paper presents an experimental study to understand the localized soft-tissue deformation phase immediately preceding crack growth as observed during the cutting of soft tissue. Such understanding serves as a building block to enable realistic haptic display in simulation of soft tissue cutting for surgical training. Experiments were conducted for soft tissue cutting with a scalpel blade while monitoring the cutting forces and blade displacement for various cutting speeds and cutting angles. The measured force-displacement curves in all the experiments of scalpel cutting of pig liver sample having a natural bulge in thickness exhibited a characteristic pattern: repeating units formed by a segment of linear loading (deformation) followed by a segment of sudden unloading (localized crack extension in the tissue). During the deformation phase immediately preceding crack extension in the tissue, the deformation resistance of the soft tissue was characterized with the local effective modulus (LEM). By iteratively solving an inverse problem formulated with the experimental data and finite element models, this measure of effective deformation resistance was determined. Then computational experiments of model order reduction were conducted to seek the most computationally efficient model that still retained fidelity. Starting with a 3-D finite element model of the liver specimen, three levels of model order reduction were carried out with computational effort in the ratio of 1.000:0.103:0.038. We also conducted parametric studies to understand the effect of cutting speed and cutting angle on LEM. Results showed that for a given cutting speed, the deformation resistance decreased as the cutting angle was varied from 90 degrees to 45 degrees. For a given cutting angle, the deformation resistance decreased with increase in cutting speed. PMID- 17355047 TI - Encoding of information into neural spike trains in an auditory nerve fiber model with electric stimuli in the presence of a pseudospontaneous activity. AB - This paper presents an information-theoretic analysis of neural spike trains in an auditory nerve fiber (ANF) model stimulated extracellularly with Gaussian or sinusoidal waveforms in the presence of a pseudospontaneous activity of spike firings. In the computer simulation, stimulus current waveforms were applied repeatedly to a stimulating electrode located 1 mm above the 26th node of Ranvier, in an ANF axon model having 50 nodes of Ranvier, each consisting of stochastic sodium and potassium channels. From spike firing times recorded at the 36th node of Ranvier, a post-stimulus time histogram (PSTH) was generated, and raster plots were depicted for 30 stimulus presentations, in order to investigate the temporal precision and reliability of the spike firing times. Also, inter spike intervals were generated and then "total" and "noise" entropies were estimated to obtain the mutual information and the information rate of the spike trains. It was shown in the case of Gaussian electric stimuli that the temporal precision of spike firing times and the reliability of spike firings were found to increase as the standard deviation (SD) of the Gaussian electric stimuli increased. It was also shown in the case of sinusoidal electric stimuli where there was a specific amplitude of sinusoidal waveforms, the information rate being maximized. It was implied that setting the parameters of electric stimuli to the specific values which maximize the information rate might contribute to efficiently encoding information into the spike trains in the presence of a pseudospontaneous activity of spike firings. PMID- 17355048 TI - A feasible application of constrained optimization in the IMRT system. AB - The planning of intensity modulated radiation therapy cancer treatment poses an inverse problem and is usually solved by optimization methods. Treatment planning, in a majority of cases, requires restrictions to be imposed on the healthy organs, sensitive to the radiation, which justifies the use of constrained optimization. The application of these techniques in treatment planning usually involves serious complications and limitations due to the huge number of variables appearing in the planning process. This leads to large computation times and memory requirements. In this paper, strategies and algorithmic issues are proposed in order to cope with these limitations. The proposed methods have been applied and tested in real cases of prostate cancer, obtaining satisfactory results regarding computational limitations. PMID- 17355049 TI - A physiologically plausible spatio-temporal model for EEG signals recorded with intracerebral electrodes in human partial epilepsy. AB - Stereoelectroencephalography (depth-EEG signals) is a presurgical investigation technique of drug-resistant partial epilepsy, in which multiple sensor intracerebral electrodes are used to directly record brain electrical activity. In order to interpret depth-EEG signals, we developed an extended source model which connects two levels of representation: (1) a distributed current dipole model which describes the spatial distribution of neuronal sources; (2) a model of coupled neuronal populations which describes their temporal dynamics. From this extended source model, depth-EEG signals were simulated from the forward solution at each electrode sensor located inside the brain. Results showed that realistic transient epileptiform activities (spikes) are obtained under specific conditions in the model in terms of degree of coupling between neuronal populations and spatial extent of the source. In particular, the cortical area involved in the generation of epileptic spikes was estimated to vary from 18 to 25 cm2, for brain conductivity values ranging from 30 to 35 x 10(-5) S/mm, for high coupling degree between neuronal populations and for a volume conductor model that accounts for the three main tissues of the head (brain, skull, and scalp). This study provides insight into the relationship between spatio-temporal properties of cortical neuronal sources and depth-EEG signals. PMID- 17355050 TI - Construction of a computer model to investigate sawtooth effects in the Purkinje system. AB - The sawtooth effect refers to how one end of a cardiac cell is depolarized, while the opposite end is hyperpolarized, upon exposure to an exogenous electric field. Although hypothesized, it has not been observed in tissue. The Purkinje system is a one-dimensional (1-D) cable-like system residing on the endocardial surface of the heart and is the most obvious candidate for the manifestation of this phenomenon. This paper describes a computer modeling study of the effect of electric fields on the Purkinje system. Starting with a three-dimensional geometrically realistic, finite element, ventricular description, a Purkinje system is constructed which adheres to general physiological principles. Electrical activity in the Purkinje is described by use of 1-D cubic Hermite finite elements. Such a formulation allows for accurate modeling of loading effects at the Purkinje-myocyte junctions, and for preserving the discrete nature of the system. The response of a strand of Purkinje cells to defibrillation strength shocks is computed under several conditions. Also, the response of the isolated Purkinje network is illustrated. Results indicate that the geometry of the Purkinje system is the greatest determinant for far field excitation of the system. Given parameters within the plausible physiological range, the 1-D nature of the Purkinje system may lead to sawtooth potentials which are large enough to affect excitation. Thus, the Purkinje system is capable of affecting the defibrillation process, and warrants further experimentation to elucidate its role. PMID- 17355051 TI - Lp norm iterative sparse solution for EEG source Localization. AB - How to localize the neural electric activities effectively and precisely from the scalp EEG recordings is a critical issue for clinical neurology and cognitive neuroscience. In this paper, based on the spatial sparse assumption of brain activities, proposed is a novel iterative EEG source imaging algorithm, Lp norm iterative sparse solution (LPISS). In LPISS, the lp (p < or =1) norm constraint for sparse solution is integrated into the iterative weighted minimum norm solution of the underdetermined EEG inverse problem, and it is the constraint and the iteratively renewed weight that forces the inverse problem to converge to a sparse solution effectively. The conducted simulation studies with comparison to LORETA and FOCUSS for various dipoles configurations confirmed the validation of LPISS for sparse EEG source localization. Finally, LPISS was applied to a real evoked potential collected in a study of inhibition of return (IOR), and the result was consistent with the previously suggested activated areas involved in an IOR process. PMID- 17355052 TI - ECG signal compression based on Burrows-Wheeler transformation and inversion ranks of linear prediction. AB - Many transform-based compression techniques, such as Fourier, Walsh, Karhunen Loeve (KL), wavelet, and discrete cosine transform (DCT), have been investigated and devised for electrocardiogram (ECG) signal compression. However, the recently introduced Burrows-Wheeler Transformation has not been completely investigated. In this paper, we investigate the lossless compression of ECG signals. We show that when compressing ECG signals, utilization of linear prediction, Burrows Wheeler Transformation, and inversion ranks yield better compression gain in terms of weighted average bit per sample than recently proposed ECG-specific coders. Not only does our proposed technique yield better compression than ECG specific compressors, it also has a major advantage: with a small modification, the proposed technique may be used as a universal coder. PMID- 17355053 TI - Construction of point process adaptive filter algorithms for neural systems using sequential Monte Carlo methods. AB - The stochastic state point process filter (SSPPF) and steepest descent point process filter (SDPPF) are adaptive filter algorithms for state estimation from point process observations that have been used to track neural receptive field plasticity and to decode the representations of biological signals in ensemble neural spiking activity. The SSPPF and SDPPF are constructed using, respectively, Gaussian and steepest descent approximations to the standard Bayes and Chapman Kolmogorov (BCK) system of filter equations. To extend these approaches for constructing point process adaptive filters, we develop sequential Monte Carlo (SMC) approximations to the BCK equations in which the SSPPF and SDPPF serve as the proposal densities. We term the two new SMC point process filters SMC-PPFs and SMC-PPFD, respectively. We illustrate the new filter algorithms by decoding the wind stimulus magnitude from simulated neural spiking activity in the cricket cercal system. The SMC-PPFs and SMC-PPFD provide more accurate state estimates at low number of particles than a conventional bootstrap SMC filter algorithm in which the state transition probability density is the proposal density. We also use the SMC-PPFs algorithm to track the temporal evolution of a spatial receptive field of a rat hippocampal neuron recorded while the animal foraged in an open environment. Our results suggest an approach for constructing point process adaptive filters using SMC methods. PMID- 17355054 TI - Parametric study of neural gastric electrical stimulation in acute canine models. AB - Manipulation of gastric motility by gastric electrical stimulation (GES) has been suggested as a minimally invasive alternative treatment of gastric motility disorders and obesity. However, only neural GES (NGES) has been successful in invoking gastric contractions. Nevertheless, the relationship between these contractions and the controlling NGES parameters has not been quantified. We aimed at determining the relationship between the electrical energy delivered to the tissue as a function of NGES parameters, and the strength and duration of the resulting invoked gastric contractions. Five healthy mongrel dogs underwent subserosal prepyloric implantation of two NGES electrode pairs. Gastric motility was captured by a force transducer implanted in the vicinity of the distal pair of stimulating electrodes. Custom-designed implantable stimulator delivered NGES with 8-16 V (peak-to-peak) amplitudes, and 60-100% duty cycles. Normalized motility index (MI) was utilized to quantify the contractions recorded from the force transducer. The MI increased with increasing voltage amplitudes. However, it remained remarkably constant across all duty cycles when voltage was held constant. Calculated motility generation efficiency indices (MGEI) indicated that highest energy efficiency for invoked motility was achieved at the lowest duty cycle. The parametric data obtained in the present study can be utilized to optimize the power efficiency of implantable gastric neurostimulators. PMID- 17355055 TI - Single-trial classification of MEG recordings. AB - While magnetoencephalography (MEG) is widely used to identify spatial locations of brain activations associated with various tasks, classification of single trials in stimulus-locked experiments remains an open subject. Very significant single-trial classification results have been published using electroencephalogram (EEG) data, but in the MEG case, the weakness of the magnetic fields originating from the relevant sources relative to external noise, and the high dimensionality of the data are difficult obstacles to overcome. We present here very significant MEG single-trial mean classification rates of words. The number of words classified varied from seven to nine and both visual and auditory modalities were studied. These results were obtained by using a variety of blind sources separation methods: spatial principal components analysis (PCA), Infomax independent components analysis (Infomax ICA) and second order blind identification (SOBI). The sources obtained were classified using two methods, linear discriminant classification (LDC) and v-support vector machine (v SVM). The data used here, auditory and visual presentations of words, presented nontrivial classification problems, but with Infomax ICA associated with LDC we obtained high classification rates. Our best single-trial mean classification rate was 60.1% for classification of 900 single trials of nine auditory words. On two-class problems rates were as high as 97.5%. PMID- 17355056 TI - Processing of multichannel recordings for data-mining algorithms. AB - Data Mining, or knowledge discovery, is the computer-assisted process of digging through and analyzing large quantity of data in order to extract meaningful knowledge. Data mining methods are used in many studies to identify phenomena quicker and better than human experts. One class of these methods was designed for dealing with time series data. However, when several channels of data are collected simultaneously, data mining algorithms encounter numerous difficulties since channels may be measured in different units, may be recorded at different sampling-rates, or may have completely different characteristics. Furthermore, as the size of these data increases, the amount of irrelevant data usually increases as well and the process becomes impractical. Hence, in such cases, the analyst must be capable of focusing on the informational parts while ignoring the noise data. These kinds of difficulties complicate the analysis of multichannel data as compared to the analysis of single-channel data. This paper presents a useful technique for preprocessing multi channel data. Our technique supplies tools for coping with all the above-mentioned difficulties, and prepares the data for further analysis (using common algorithms, especially from the data mining field). The paper is divided as follows. After the introduction (Section I) we describe the state of the art (Section II), follows by the main section methodology (Section III) which is divided to four steps (3.2-3.5). The results are described in a separate section (Section IV). Then, a discussion and conclusions of the proposed methodology are given in (Sections V and VI). Acknowledgements and the references follow. PMID- 17355057 TI - Quantification of unidirectional nonlinear associations between multidimensional signals. AB - In this paper, we present a rigorous, general definition of the nonlinear association index, known as h2. Proving equivalence between different definitions we show that the index measures the best dynamic range of any nonlinear map between signals. We present also a construction for removing the influence of one signal from another, providing, thus, the basis of an independent component analysis. Our definition applies to arbitrary multidimensional vector-valued signals and depends on an aperture function. In this way, the bin-related classic definition of h2 can be generalized. We show that upon choosing suitable aperture functions the bin-related intuitive definition can be deduced. Special attention is dedicated to the direction of the association index that in general is taken in only one sense. We show that for linearly coupled signals high associations are always bidirectional. As a consequence, high asymmetric nonlinear associations are indicators of nonlinear relations, possibly critical, between the dynamic systems underlying the measured signals. We give a simple simulated example to illustrate this property. As a potential clinical application, we show that unidirectional associations between electroencephalogram (EEG) and electromyogram (EMG) recorded from patient with pharmacologically intractable epilepsy can be used to study the cortical involvement in the generation of motor seizures. PMID- 17355058 TI - A model-based deconvolution approach to solve fiber crossing in diffusion weighted MR imaging. AB - A deconvolution approach is presented to solve fiber crossing in diffusion magnetic resonance imaging. In order to provide a direct physical interpretation of the signal generation process, we started from the classical multicompartment model and rewrote this in terms of a convolution process, identifying a significant scalar parameter alpha to characterize the physical system response. Deconvolution is performed by a modified version of the Richardson-Lucy algorithm. Simulations show the ability of this method to correctly separate fiber crossing, even in the presence of noisy data, with lower signal-to-noise ratio, and imprecision in the impulse response function imposed during deconvolution. The in vivo data confirms the efficacy of this method to resolve fiber crossing in real complex brain structures. These results suggest the usefulness of our approach in fiber tracking or connectivity studies. PMID- 17355059 TI - Automated optic disk boundary detection by modified active contour model. AB - This paper presents a novel deformable-model-based algorithm for fully automated detection of optic disk boundary in fundus images. The proposed method improves and extends the original snake (deforming-only technique) in two aspects: clustering and smoothing update. The contour points are first self-separated into edge-point group or uncertain-point group by clustering after each deformation, and these contour points are then updated by different criteria based on different groups. The updating process combines both the local and global information of the contour to achieve the balance of contour stability and accuracy. The modifications make the proposed algorithm more accurate and robust to blood vessel occlusions, noises, ill-defined edges and fuzzy contour shapes. The comparative results show that the proposed method can estimate the disk boundaries of 100 test images closer to the groundtruth, as measured by mean distance to closest point (MDCP) <3 pixels, with the better success rate when compared to those obtained by gradient vector flow snake (GVF-snake) and modified active shape models (ASM). PMID- 17355060 TI - A new lumped-parameter model of cerebrospinal hydrodynamics during the cardiac cycle in healthy volunteers. AB - Our knowledge of cerebrospinal fluid (CSF) hydrodynamics has been considerably improved with the recent introduction of phase-contrast magnetic resonance imaging (phase-contrast MRI), which can provide CSF and blood flow measurements throughout the cardiac cycle. Key temporal and amplitude parameters can be calculated at different sites to elucidate the role played by the various CSF compartments during vascular brain expansion. Most of the models reported in the literature do not take into account CSF oscillation during the cardiac cycle and its kinetic energy impact on the brain. We propose a new lumped-parameter compartmental model of CSF and blood flows in healthy subjects during the cardiac cycle. The system was divided into five submodels representing arterial blood, venous blood, ventricular CSF, cranial subarachnoid space, and spinal subarachnoid space. These submodels are connected by resistances and compliances. The model developed was used to reproduce certain functional characteristics observed in seven healthy volunteers, such as the distribution (amplitude and phase shift) of arterial, venous, and CSF flows. The results show a good agreement between measured and simulated intracranial CSF and blood flows. PMID- 17355061 TI - Worst case temperature rise in a one-dimensional tissue model exposed to radiofrequency radiation. AB - This paper investigates the temperature rise in a 1-D layered tissue model, which is irradiated with nonionizing radiation. Of the numerous tissue configurations that correspond to realistic body trunk and limb representations, only those are examined which maximize the averaged specific absorption rate (SAR). The results show that the old IEEE standard on safety was more conservative in terms of temperature rise than the Non-Ionizing Radiation Protection guidelines. They also indicate that the removal of heat exchange from the skin surface can induce a significant temperature rise in it, which is, however, mostly due to imposing the adiabatic conditions themselves, rather than the electromagnetic energy absorption. PMID- 17355062 TI - Low-frequency dosimetry of inhomogeneous magnetic fields using the coil source model and the household appliance. AB - In this paper, the magnetic field properties and the dosimetry at ELF (50 Hz) are investigated using a coil model, which is prescribed in the European standard EN50366 (CENELEC) as a substitute source model for real household appliances. The accuracy of magnetic field vectors and values of the induced current density, which is achieved with the coil model, were compared with the results of two test appliances (a drilling machine and a hand mixer) obtained from the equivalent source model. It was demonstrated that the magnetic fields obtained (dominant component and strength) using the coil model and the real appliance show an agreement with each other with a maximum difference of 5 dB. The calculated induced current densities in the numerical human body models (homogeneous and anatomical body models) and the real appliances also show a good agreement with each other with a maximum difference by a factor of 1.6 (by the anatomical body model). Furthermore, the values of both field vectors and induced current density values calculated using the coil model were shown to be higher than those calculated in the case of the real appliances. Based on these results, the applicability of the coil model prescribed in EN50366 confirms that of the two applied test appliances. PMID- 17355063 TI - Taser dart-to-heart distance that causes ventricular fibrillation in pigs. AB - Electromuscular incapacitating devices (EMDs), such as Tasers, deliver high current, short duration pulses that cause muscular contractions and temporarily incapacitate the human subject. Some reports suggest that EMDs can kill. To help answer the question, "Can the EMD directly cause ventricular fibrillation (VF)?", ten tests were conducted to measure the dart-to-heart distance that causes VF in anesthetized pigs [mass = 64 kg +/- 6.67 standard deviation (SD)] for the most common X26 Taser. The dart-to-heart distance that caused VF was 17 mm +/- 6.48 (SD) for the first VF event and 13.7 mm +/- 6.79 (SD) for the average of the successive VF events. The result shows that when the stimulation dart is close enough to the heart, X26 Taser current will directly trigger VF in pigs. Echocardiography of erect humans shows skin-to-heart distances from 10 to 57 mm (dart-to-heart distances of 1-48 mm). These results suggest that the probability of a dart on the body landing in 1 cm2 over the ventricle and causing VF is 0.000172. PMID- 17355064 TI - A new means of transcutaneous coupling for neural prostheses. AB - Neural prostheses are electronic stimulators that activate nerves to restore sensory or motor functions. Implanted neural prostheses receive command signals and in some cases energy to recharge their batteries through the skin by telemetry. Here, we describe a new approach that eliminates the implanted stimulator. Stimulus pulse trains are passed between two surface electrodes placed on the skin. An insulated lead with conductive terminals at each end is implanted inside the body. One terminal is located under the cathodal surface electrode and the other is attached to a nerve targeted for stimulation. A fraction (10%-15%) of the current flowing between the surface electrodes is routed through the implanted lead. The nerve is stimulated when the amount of routed current is sufficient. The aims of this study were to establish some basic electrical properties of the system and test long-term stability in chronic implants. Stimulation of the nerve innervating the ankle flexors produced graded force over the full physiological range at amplitudes below threshold for evoking muscle contractions under the surface electrodes. Implants remained stable for over 8 mo. The findings provide the basis for a new family of neural prostheses. PMID- 17355065 TI - Preprocessing and meta-classification for brain-computer interfaces. AB - A brain-computer interface (BCI) is a system which allows direct translation of brain states into actions, bypassing the usual muscular pathways. A BCI system works by extracting user brain signals, applying machine learning algorithms to classify the user's brain state, and performing a computer-controlled action. Our goal is to improve brain state classification. Perhaps the most obvious way to improve classification performance is the selection of an advanced learning algorithm. However, it is now well known in the BCI community that careful selection of preprocessing steps is crucial to the success of any classification scheme. Furthermore, recent work indicates that combining the output of multiple classifiers (meta-classification) leads to improved classification rates relative to single classifiers (Dornhege et al., 2004). In this paper, we develop an automated approach which systematically analyzes the relative contributions of different preprocessing and meta-classification approaches. We apply this procedure to three data sets drawn from BCI Competition 2003 (Blankertz et al., 2004) and BCI Competition III (Blankertz et al., 2006), each of which exhibit very different characteristics. Our final classification results compare favorably with those from past BCI competitions. Additionally, we analyze the relative contributions of individual preprocessing and meta-classification choices and discuss which types of BCI data benefit most from specific algorithms. PMID- 17355066 TI - A state-space framework for movement control to dynamic goals through brain driven interfaces. AB - State-space estimation is a convenient framework for the design of brain-driven interfaces, where neural activity is used to control assistive devices for individuals with severe motor deficits. Recently, state-space approaches were developed to combine goal planning and trajectory-guiding neural activity in the control of reaching movements of an assistive device to static goals. In this paper, we extend these algorithms to allow for goals that may change over the course of the reach. Performance between static and dynamic goal state equations and a standard free movement state equation is compared in simulation. Simulated trials are also used to explore the possibility of incorporating activity from parietal areas that have previously been associated with dynamic goal position. Performance is quantified using mean-square error (MSE) of trajectory estimates. We also demonstrate the use of goal estimate MSE in evaluating algorithms for the control of goal-directed movements. Finally, we propose a framework to combine sensor data and control algorithms along with neural activity and state equations, to coordinate goal-directed movements through brain-driven interfaces. PMID- 17355067 TI - Feasibility of an electrode-reservoir device for transdermal drug delivery by noninvasive skin electroporation. AB - Electrical creation of aqueous pathways across the skin's outer layer [stratum corneum (SC)] provides an approach to transdermal delivery of medium-size water soluble compounds. However, nerve stimulation should be avoided. Here, we show that a microstructured electrode array can significantly confine the electric field to the nerve-free SC. The prototype electrode-reservoir device (ERD) contains field-confining electrodes and a fluorescent drug surrogate [sulphorhodamine (SR)]. In vivo human experiments at the forearm with approximately rectangular voltage pulses up to 500 V and 1-ms duration cause electroporation as measured by skin resistance change but only rarely caused sensation. Human skin in vitro experiments with such pulses up to 300 V transported SR across the SC. Our results are supported by a model's prediction of the field in the ERD and nearby tissue. PMID- 17355068 TI - Simulation of biphasic CT findings in hepatic cellular carcinoma by a two-level physiological model. AB - In this paper, we present a two-level physiological model that is able to reflect morphology and function of vascular networks, in clinical images. Our approach results from the combination of a macroscopic model, providing simulation of the growth and pathological modifications of vascular network, and a microvascular model, based on compartmental approach, which simulates blood and contrast medium transfer through capillary walls. The two-level model is applied to generate biphasic computed tomography of hepatocellular carcinoma. A contrast-enhanced sequence of simulated images is acquired, and enhancement curves extracted from normal and tumoral regions are compared to curves obtained from in vivo images. The model offers the potential of finding early indicators of disease in clinical vascular images. PMID- 17355069 TI - Cancellation of ventricular activity in the ECG: evaluation of novel and existing methods. AB - Due to the much higher amplitude of the electrical activity of the ventricles in the surface electrocardiogram (ECG), its cancellation is crucial for the analysis and characterization of atrial fibrillation. In this paper, two different methods are proposed for this cancellation. The first one is an average beat subtraction type of method. Two sets of templates are created: one set for the ventricular depolarization waves and one for the ventricular repolarization waves. Next, spatial optimization (rotation and amplitude scaling) is applied to the QRS templates. The second method is a single beat method that cancels the ventricular involvement in each cardiac cycle in an independent manner. The estimation and cancellation of the ventricular repolarization is based on the concept of dominant T and U waves. Subsequently, the atrial activities during the ventricular depolarization intervals are estimated by a weighted sum of sinusoids observed in the cleaned up segments. ECG signals generated by a biophysical model as well as clinical ECG signals are used to evaluate the performance of the proposed methods in comparison to two standard ABS-based methods. PMID- 17355070 TI - Possible four-electrode configurations for measuring cardiac tissue fiber rotation. AB - A number of electrode configurations, based on the usual four-electrode probe, are analysed in relation to the effect that changes in cardiac fiber rotation have on the potentials measured. Simulations are carried out using a mathematical model and a new solution technique, based on Fourier series followed by a simple one-dimensional finite difference scheme. This electrode analysis leads to the proposal of an in-principle method for determining cardiac fiber rotation. PMID- 17355071 TI - Study of on-line adaptive discriminant analysis for EEG-based brain computer interfaces. AB - A study of different on-line adaptive classifiers, using various feature types is presented. Motor imagery brain computer interface (BCI) experiments were carried out with 18 naive able-bodied subjects. Experiments were done with three two class, cue-based, electroencephalogram (EEG)-based systems. Two continuously adaptive classifiers were tested: adaptive quadratic and linear discriminant analysis. Three feature types were analyzed, adaptive autoregressive parameters, logarithmic band power estimates and the concatenation of both. Results show that all systems are stable and that the concatenation of features with continuously adaptive linear discriminant analysis classifier is the best choice of all. Also, a comparison of the latter with a discontinuously updated linear discriminant analysis, carried out in on-line experiments with six subjects, showed that on line adaptation performed significantly better than a discontinuous update. Finally a static subject-specific baseline was also provided and used to compare performance measurements of both types of adaptation. PMID- 17355072 TI - Estimation of the uncertainty in time domain indices of RR time series. AB - A method for estimating the uncertainty in time-domain indices of RR time series is described. The method relies on the central limit theorem that states that the distribution of a sample average of independent samples has an uncertainty that asymptotically approaches to the sample standard deviation divided by the square root of the number of samples. Because RR time series cannot be characterized by a set of independent samples, we propose to estimate the uncertainty of indices by computing them in blocks that satisfy that the obtained partial indices are independent. We propose a methodology to search sets of independent partial indices and apply this methodology to the estimation of the uncertainty in the mean RR, SDRR, and r-msDD indices. The results show that the uncertainty can be higher than the 10% of the index for the SDRR and even higher for the r-msDD. Moreover, a statistical test for the difference of two indices is proposed. PMID- 17355073 TI - Selective activation of distant nerve by surface electrode array. AB - Neural prostheses for restoring lost functions can benefit from selective activation of nerves with limited number and density of electrodes. Here, we show by simulations and animal experiments that multipoint simultaneous stimulation with a surface electrode array can selectively activate nerves in a bundle at a desired location in between the array or at a desired depth, which are referred to as lateral or depth-wise gating stimulation, respectively. The stimulation broadly generates action potentials with cathodic source electrodes, and simultaneously blocks unnecessary propagation with downstream anodic gate electrodes. In general, stimulation with a small diameter electrode can affect a nearly hemispherical region, while a large electrode is effective at a more vertically compressed region, i.e., a surface of nerve bundle. The gating stimulation takes advantage of the size effects by utilizing an asymmetrical electrode array. The array of the lateral gating stimulation is designed to have four electrodes; a pair of large source electrodes and a pair of small gate electrodes. The depth-wise gating stimulation array consists of two electrodes; a large gate and small source electrodes. The simulation first demonstrated that appropriate combination of currents at the source and gate electrodes can change recruitment patterns of nerves with lateral or depth-wise selectivity as desired. We then applied the lateral gating stimulation on the rat spinal cords and obtained a preliminary support for the feasibility. PMID- 17355074 TI - Real-world vehicle emissions: a summary of the Sixteenth Coordinating Research Council On-Road Vehicle Emissions Workshop. AB - The Coordinating Research Council held its 16th workshop in March 2006, with 83 presentations describing the most recent mobile source-related emissions research. In this paper, we summarize the presentations from researchers who are engaged in improving our understanding of the contribution of mobile sources to air quality. Participants in the workshop discussed evaluation of in-use emissions control programs, effects of fuels on emissions, emission models and emission inventories, results from gas- and particle-phase emissions studies from spark-ignition and diesel-powered vehicles, and efforts to improve our capabilities in performing on-board emissions measurements, as well as topics for future research. PMID- 17355075 TI - Receptor modeling of ambient particulate matter data using positive matrix factorization: review of existing methods. AB - Methods for apportioning sources of ambient particulate matter (PM) using the positive matrix factorization (PMF) algorithm are reviewed. Numerous procedural decisions must be made and algorithmic parameters selected when analyzing PM data with PMF. However, few publications document enough of these details for readers to evaluate, reproduce, or compare results between different studies. For example, few studies document why some species were used and others not used in the modeling, how the number of factors was selected, or how much uncertainty exists in the solutions. More thorough documentation will aid the development of standard protocols for analyzing PM data with PMF and will reveal more clearly where research is needed to help future analysts select from the various possible procedures and parameters available in PMF. For example, research likely is needed to determine optimal approaches for handling data below detection limits, ways to apportion PM mass among sources identified by PMF, and ways to estimate uncertainties in the solution. The review closes with recommendations for documenting the methodological details of future PMF analyses. PMID- 17355076 TI - The role of mechanical and biological treatment in reducing methane emissions from landfill disposal of municipal solid waste in the United Kingdom. AB - In Europe, the European Union Landfill Directive aims to reduce the negative environmental impacts of landfilling. This is mainly to be achieved by reducing the quantity of organic matter deposited, through measures such as the separate collection and recycling of the organic waste stream or pretreatment of residual wastes before landfilling. Other than incineration or other thermal processes, mechanical biological treatment is playing an increasingly important role. This study was conducted to seek the benefits of municipal solid waste (MSW) pretreatment, as well as the differences in methane production from the landfilling of untreated and mechanically/biologically treated (MBT) MSW using GasSim simulation. Results demonstrated that methane production rates vary significantly among waste fractions. Those that contribute most to methane generation (organic material and potentially reusable or recyclable material) could be targeted and treated before landfilling. The statistic relationship from the first phase of the study indicated that to match the increasingly stringent landfill waste organic content allowance, local councils should prioritize the reduction/sorting of certain targeted fractions, such as paper, card, green waste, and other putrescibles from MSW. Moreover, mechanical treatment alone produces organic-rich waste called mechanically sorted organic residues (MSORs), which can be viewed as an organic content concentration process. Mechanically and biologically pretreated waste, on the other hand, differs significantly from untreated MSW and MSORs. This work demonstrated that if efficient mechanical biological treatment is used, considerable reductions in biological activity, landfill gas production, and energy content/total organic carbon could be achieved. Using GasSim, reductions in methane production of >74% have been simulated if a 90% organic content reduction can be achieved during biological treatment on MSORs. A 50-60% organic content reduction by following biological treatment can turn MSOR properties only into normal MSW equivalent though considerably less volume. PMID- 17355077 TI - Source analysis of particulate-phase polycyclic aromatic hydrocarbons in an urban atmosphere of a northern city in China. AB - Particle-associated polycyclic aromatic hydrocarbon (PAH) concentrations were investigated at six sampling sites in the heating (February to March 2001) and nonheating (August to September 2001) periods in an industrial city in Northern China. Thirteen PAHs were measured. The total average concentrations (nanograms per meter cubed) of PAHs ranged between 78.93 and 214.63 during the heating period and from 31.48 to 102.26 in the nonheating period. Benzo(a)pyrene occurred at the highest level at a site near an industrial area but occurred at low concentrations far from the city center and industrial areas. In addition, ambient PAH profiles were studied. The five and six-ring species occurred in high fractions at the sampling site. By diagnostic ratio analysis, the major source at each sampling site in the city was coal combustion in the heating period; in the nonheating period, the major sources were relatively complex. Finally, the similarities among the six regions were assessed by principal component analysis, cluster analysis, and coefficient of divergence. These multivariate statistical analyses produced similar results, which agreed with the results from the diagnostic ratio analysis. PMID- 17355078 TI - The viability of professional wet cleaning as a pollution prevention alternative to perchloroethylene dry cleaning. AB - The vast majority of dry cleaners worldwide use the toxic chemical perchloroethylene (PCE), which is associated with a number of adverse health and environmental impacts. Professional wet cleaning was developed as a nontoxic alternative to PCE dry cleaning but has not been widely adopted as substitute technology. In the greater Los Angeles, CA, region, a demonstration project was set up to showcase this technology and evaluate its commercial viability by converting seven cleaners from PCE dry cleaning to professional wet cleaning. The demonstration site cleaners who switched to professional wet cleaning were able to maintain their level of service and customer base while lowering operating costs. The cleaners were able to transition to professional wet cleaning without a great degree of difficulty and expressed a high level of satisfaction with professional wet cleaning. Crucial to this success was the existence of the demonstration project, which helped to develop a supporting infrastructure for professional wet cleaning that had otherwise been lacking in the garment care industry. PMID- 17355079 TI - Numerical study of the effect of ventilation pattern on coarse, fine, and very fine particulate matter removal in partitioned indoor environment. AB - An indoor size-dependent particulate matter (PM) transport approach is developed to investigate coarse PM (PM10), fine PM (PM2.5), and very fine PM (PM1) removal behaviors in a ventilated partitioned indoor environment. The approach adopts the Eulerian large eddy simulation of turbulent flow and the Lagrangian particle trajectory tracking to solve the continuous airflow phase and the discrete particle phase, respectively. Model verification, including sensitivity tests of grid resolution and particle numbers, is conducted by comparison with the full size experiments conducted previously. Good agreement with the measured mass concentrations is found. Numerical scenario simulations of the effect of ventilation patterns on PM removal are performed by using three common ventilation patterns (piston displacement, mixing, and cross-flow displacement ventilation) with a measured indoor PM10 profile in the Taipei metropolis as the initial condition. The temporal variations of suspended PM10, PM2.5, and PM1 mass concentrations and particle removal mechanisms are discussed. The simulated results show that for all the of the three ventilation patterns, PM2.5 and PM1 are much more difficult to remove than PM10. From the purpose of health protection for indoor occupants, it is not enough to only use the PM10 level as the indoor PM index. Indoor PM2.5 and PM1 levels should be also considered. Cross flow displacement ventilation is more effective to remove all PM10, PM2.5, and PM1 than the other ventilation patterns. Displacement ventilation would result in more escaped particles and less deposited particles than mixing ventilation. PMID- 17355080 TI - Factor analysis of submicron particle size distributions near a major United States-Canada trade bridge. AB - A factor analytic model has been applied to resolve and apportion particles based on submicron particle size distributions downwind of a United States-Canada bridge in Buffalo, NY. The sites chosen for this study were located at gradually increasing distances downwind of the bridge complex. Seven independent factors were resolved, including four factors that were common to all of the five sites considered. The common factors were generally characterized by the existence of two or more number and surface area modes. The seven factors resolved were identified as follows: fresh tail-pipe diesel exhaust, local/street diesel traffic, aged/evolved diesel particles, spark-ignition gasoline emissions, background urban emissions, heavy-duty diesel agglomerates, and secondary/transported material. Submicron (<0.5 microm) and ultrafine (<0.1 microm) particle emissions downwind of the bridge were dominated by commercial diesel truck emissions. Thus, this study obtained size distinction between fresh versus aged vehicle exhaust and spark-ignition versus diesel emissions based on the measured high time-resolution particle number concentrations. Because this study mainly used particles <300 nm in diameter, some sources that would usually exhibit number modes >100 nm were not resolved. Also, the resolved profiles suggested that the major number mode for fresh tailpipe diesel exhaust might exist below the detection limit of the spectrometer used. The average particle number contributions from the resolved factors were highest closest to the bridge. PMID- 17355081 TI - Silane removal at ambient temperature by using alumina-supported metal oxide adsorbents. AB - Copper, zinc, and cerium oxide adsorbents supported on alumina were used to remove silane gas (SiH4). The adsorbents were prepared using a coprecipitation method and characterized by the inductively coupled plasma mass spectrometry, X ray powder diffractometer, and Brunauer-Emmett-Teller method (BET). The silane removal efficiency and adsorption capacity of the adsorbents were investigated in this study. Test results showed that the adsorbents containing active species had a removal efficiency >99.9% for SiH4 before breakthrough. Adsorbents containing mixed oxides (CuO-CeO2/ Al2O3 and CuO-ZnO/Al2O3), which showed well-dispersed active species and high BET surface areas, had a greater adsorption capacity than the adsorbents containing single metal oxide. However, when the CuO-ZnO/ Al2O3 adsorbents contain >40 wt% of active metal oxides, the increase of active species lowered the BET surface area leading to a decrease of the adsorption capacity. Additionally, when the content of the active metal oxides was between 20% and 40%, the CuO-ZnO/Al2O3 adsorbents demonstrated higher adsorption capacity. PMID- 17355082 TI - Use of the electrical aerosol detector as an indicator of the surface area of fine particles deposited in the lung. AB - Because of recent concerns about the health effects of ultrafine particles and the indication that particle toxicity is related to surface area, we have been examining techniques for measuring parameters related to the surface area of fine particles, especially in the 0.003- to 0.5-microm size range. In an earlier study, we suggested that the charge attached to particles, as measured by a prototype of the Electrical Aerosol Detector (EAD, TSI Inc., Model 3070), was related to the 1.16 power of the mobility diameter. An inspection of the pattern of particle deposition in the lung as a function of particle size suggested that the EAD measurement might be a useful indicator of the surface area of particles deposited in the lung. In this study, we calculate the particle surface area (micrometer squared) deposited in the lung per cubic centimeter of air inhaled as a function of particle size using atmospheric particle size distributions measured in Minneapolis, MN, and East St. Louis, IL. The correlations of powers of the mobility diameter, Dx, were highest for X = 1.1-1.6 for the deposited surface area and for X = 1.25 with the EAD signal. This overlap suggested a correspondence between the EAD signal and the deposited surface area. The correlation coefficients of the EAD signal and particle surface area deposited in the alveolar and tracheobronchial regions of the lung for three breathing patterns are in the range of Pearson's r = 0.91-0.95 (coefficient of determination, R2 = 0.82-0.90). These statistical relationships suggest that the EAD could serve as a useful indicator of particle surface area deposited in the lung in exposure and epidemiologic studies of the human health effects of atmospheric particles and as a measure of the potential surface area dose for the characterization of occupational environments. PMID- 17355083 TI - Remediation of soil contaminated with pyrene using ground nanoscale zero-valent iron. AB - The sites contaminated with recalcitrant polycyclic aromatic hydrocarbons (PAHs) are serious environmental problems ubiquitously. Some PAHs have proven to be carcinogenic and hazardous. Therefore, the innovative PAH in situ remediation technologies have to be developed instantaneously. Recently, the nanoscale zero valent iron (ZVI) particles have been successfully applied for dechlorination of organic pollutants in water, yet little research has investigated for the soil remediation so far. The objective in this work was to take advantage of nanoscale ZVI particles to remove PAHs in soil. The experimental factors such as reaction time, particle diameter and iron dosage and surface area were considered and optimized. From the results, both microscale and nanoscale ZVI were capable to remove the target compound. The higher removal efficiencies of nanoscale ZVI particles were obtained because the specific surface areas were about several dozens larger than that of commercially microscale ZVI particles. The optimal parameters were observed as 0.2 g iron/2 mL water in 60 min and 150 rpm by nanoscale ZVI. Additionally, the results proved that nanoscale ZVI particles are a promising technology for soil remediation and are encouraged in the near future environmental applications. Additionally, the empirical equation developed for pyrene removal efficiency provided the good explanation of reaction behavior. Ultimately, the calculated values by this equation were in a good agreement with the experimental data. PMID- 17355084 TI - Source apportionment of daily fine particulate matter at Jefferson Street, Atlanta, GA, during summer and winter. AB - The primary emission source contributions to fine organic carbon (OC) and fine particulate matter (PM2.5) mass concentrations on a daily basis in Atlanta, GA, are quantified for a summer (July 3 to August 4, 2001) and a winter (January 2 31, 2002) month. Thirty-one organic compounds in PM2.5 were identified and quantified by gas chromatography/mass spectrometry. These organic tracers, along with elemental carbon, aluminum, and silicon, were used in a chemical mass balance (CMB) receptor model. CMB source apportionment results revealed that major contributors to identified fine OC concentrations include meat cooking (7 68%; average: 36%), gasoline exhaust (7-45%; average: 21%), and diesel exhaust (6 41%; average: 20%) for the summer month, and wood combustion (0-77%; average: 50%); gasoline exhaust (14-69%; average: 33%), meat cooking (1-14%; average: 5%), and diesel exhaust (0-13%; average: 4%) for the winter month. Primary sources, as well as secondary ions, including sulfate, nitrate, and ammonium, accounted for 86 +/- 13% and 112 +/- 15% of the measured PM2.5 mass in summer and winter, respectively. PMID- 17355085 TI - Analysis of long-term settlement of municipal solid waste landfills as determined by various settlement estimation methods. AB - In this study, several existing municipal solid waste (MSW) settlement estimation methods are reviewed and applied to analyze the settlement data of nine MSW landfills. Because a biodegradation-related settlement contributes differently to a long-term total settlement depending on the age of landfills, the actual MSW landfill sites are classified into three groups to specifically address the validity of each method in its prediction of a long-term settlement for each age category. Results demonstrate that there are considerable decreases in predicted settlement potentials as fill age increases. Comparisons indicate that the individual estimation methods display a considerable variation in predicting settlements in the fresh MSW landfills. On the other hand, for the old refuse landfills, all of the estimation methods, except the extended soil model, predict low settlement potentials. PMID- 17355086 TI - Emissions of chromium (VI) from arc welding. AB - The presence of Cr in the +6 oxidation state (Cr[VI]) is still observed in ambient air samples in California despite steps taken to reduce emissions from plating operations. One known source of emission of Cr(VI) is welding, especially with high Cr-content materials, such as stainless steels. An experimental effort was undertaken to expand and update Cr(VI) emission factors by conducting tests on four types of arc-welding operations: gas-metal arc welding (GMAW), shielded metal arc welding (SMAW), fluxcore arc welding, and pulsed GMAW. Standard American Welding Society hood results were compared with a total enclosure method that permitted isokinetic sampling for particle size-cut measurement, as well as total collection of the aerosol. The fraction of Cr(VI) emitted per unit mass of Cr electrode consumed was determined. Consistent with AP-42 data, initial results indicate that a significant fraction of the total Cr in the aerosol is in the +6 oxidation state. The fraction of Cr(VI) and total aerosol mass produced by the different arc welding methods varies with the type of welding process used. Self shielded electrodes that do not use a shield gas, for example, SMAW, produce greater amounts of Cr(VI) per unit mass of electrode consumed. The formation of Cr(VI) from standard electrode wires used for welding mild steel was below the method detection limit after eliminating an artifact in the analytical method used. PMID- 17355087 TI - Acute and chronic hepatitis. AB - Most liver biopsies performed today are for grading and staging of chronic viral hepatitis and steatohepatitis; there are uncommon indications for liver biopsy in the setting of acute hepatitis. Pathologists must have a broad knowledge of many forms of acute and chronic hepatitis, as well as their variations; these include viral hepatitis, autoimmune hepatitis, drug-induced hepatitis, metabolic diseases, and reactive hepatitis secondary to systemic disease processes. In this article, the authors review the pathological features of acute and chronic hepatitis. PMID- 17355088 TI - Alcoholic liver disease. AB - Alcohol excess is associated with a spectrum of disease ranging from simple steatosis through steatohepatitis to cirrhosis and, in some, hepatocellular carcinoma. Alcoholic steatohepatitis itself has a variable histological picture, but a constant feature is the presence of ballooning degeneration of hepatocytes. Recent studies have emphasized the importance of apoptosis as a mechanism of cell death in this condition. It is accompanied by varying degrees of perivenular, centrilobular, and pericellular fibrosis. When severe and associated with perivenular liver cell necrosis (central sclerosing hyaline necrosis), there may be precirrhotic portal hypertension. The pattern of fibrosis may initially be diffuse with little nodule formation, but in time there is frequently the development of a micronodular cirrhosis. In approximately 15% of patients with established cirrhosis, hepatocellular carcinoma develops; several precursor lesions are now recognized which can be detected histologically. Several authors have drawn attention to additional components of the spectrum of alcoholic liver disease, including vascular changes, portal tract inflammation and fibrosis, ductular reaction, and iron overload. The morphology of alcoholic liver disease can be significantly affected by abstinence; furthermore, the clinical and morphological phenotype can be significantly influenced by the presence of comorbid conditions such as nonalcoholic fatty liver disease or viral hepatitis. Biopsy appearances can provide important prognostic information in alcoholic liver disease, and this review incorporates a proposed grading and staging schema for assessment of histological severity. PMID- 17355089 TI - Granulomas in the liver. AB - Granulomatous diseases of the liver span a huge range of infectious, drug related, and immunologic disorders. Familiarity with the different types of granulomas as well as how they present in different diseases can be helpful in narrowing the pathologic differential diagnosis. This review surveys both common and unusual granulomatous diseases with emphasis on practical diagnosis. PMID- 17355090 TI - Transplantation pathology. AB - Histological assessments continue to have an important role in the diagnosis and management of graft complications following liver transplantation. For some conditions, such as liver allograft rejection, histology is regarded as the "gold standard" for diagnosis. In other cases, where a likely cause of graft dysfunction has been identified using other methods, liver biopsy provides important additional information (e.g., severity of necroinflammatory activity and fibrosis in recurrent hepatitis C infection) and may point to the presence of an additional or alternative cause for graft dysfunction. In cases where a dual pathology is suspected (eg, hepatitis C and rejection), histological findings can help to identify the main cause of graft dysfunction. This article will focus on the main patterns of damage that are seen in post-transplant liver biopsies and their differential diagnosis. As with the assessment of liver biopsies in the native liver, clinico-pathological correlation is very important. Consideration should also be given to the therapeutic implications of the biopsy report, in particular whether changes in immunosuppression are indicated. PMID- 17355091 TI - Hepatitic inherited metabolic disorders. AB - Primary metabolic disorders are a disparate group of diseases that may or may not be accompanied by hepatic manifestations. Those with liver involvement may show a range of histopathologic changes. Proper histologic diagnosis requires correlation with clinical and laboratory data, including evaluation for mutations either via serum protein electrophoresis or through formal genetic analysis. This article is a review of the three most common inherited metabolic disorders which may present with a hepatitic pattern. In alpha1-antitrypsin disorder, there is a broad range of clinical presentations, age at presentation, and histological features ranging from "neonatal hepatitis" to a chronic progressive hepatitis in later childhood and adulthood. Hence, this disorder must be in the differential diagnosis of liver disease of the very young, and in older children and adults, with or without coexistent overt pulmonary symptoms. In Wilson disease, presentation tends to be in older childhood or the adult, with a progressive chronic hepatitis. Cystic fibrosis may feature a characteristic obstructive biliary syndrome, coexisting with the many extrahepatic manifestations of this debilitating disease. Lastly, the progressive familial intrahepatic cholestasis (PFIC) syndromes are given as examples of inherited metabolic conditions in which relentlessly progressive cholestatic liver disease eventuates over years in end stage cholestatic liver disease with cirrhosis. Distinguishing features include absence of elevated serum gamma-glutamyl transpeptidase (GGT) in PFIC-1 and PFIC 2, and elevated GGT in PFIC-3. However, molecular studies are required for a confident diagnosis of the rare PFIC syndromes. PMID- 17355092 TI - Special stains in diagnostic liver pathology. AB - The comprehensive histopathologic evaluation of liver tissue, including biopsy, explant, and postmortem specimens, utilizes a standard panel of special histochemical stains as well as selective immunohistochemistry. These methods provide increased accuracy in addressing common diagnostic problems such as determining the stage of fibrosis in chronic hepatitis, documenting the presence of cirrhosis or other causes of portal hypertension, iron, and copper overload, disorders of the biliary tract, and tumor histogenesis. This review discusses the indications for various staining methods and the specific uses of trichrome and reticulin connective tissue stains, periodic acid-Schiff (PAS) and diastase pretreated PAS (DPAS), iron, and Victoria blue methods. Diagnostic applications of immunohistochemical stains are also described. PMID- 17355093 TI - Sterilisation of intellectually disabled minors. AB - The complex issue of sterilisation of minors with intellectual disabilities has arisen again for Australia with proposals for a uniform approach by the Standing Committee of Attorneys-General under which the principal forum for decision making about such matters will be State and Territory administrative tribunals. This provides an opportunity not just for scrutiny of the proposed legislation and model but evaluation of the role of decision-making bodies, their procedural supports and the criteria on the basis of which sterilisations of young people should be authorised by Australia's courts and tribunals. The opportunity exists for an approach to be forged on the basis of empirical assessment of the success of administrative tribunal involvement, understanding of the phenomenon of "therapeutic" and "non-therapeutic" sterilisation of minors in contemporary Australia and current medical and psychological awareness of ways to manage menstruation and the potential for pregnancy for vulnerable young people. PMID- 17355094 TI - Professional disciplinary proceedings against expert medical witnesses. AB - Witnesses in legal proceedings are protected from civil liability based on their evidence. This immunity is founded on public policy considerations, particularly the belief that witnesses would be less willing to provide full and frank evidence if they were at the risk of civil proceedings based on their evidence. But witness immunity now appears to be subject to an important qualification. The English Court of Appeal has confirmed that witness immunity does not prevent the commencement of professional disciplinary proceedings against an expert witness. In General Medical Council v Meadow [2006] EWCA 1390 the court upheld a disciplinary complaint made against an expert medical witness, even though the complaint was based on that doctor's witness evidence. The Court of Appeal reasoned that the underlying purpose of professional disciplinary proceedings, which is to protect the public, could sit comfortably with witness immunity. The result seems to be that people unhappy with witness evidence cannot sue the witness but can make a professional disciplinary complaint. This apparent gap in witness immunity is important to all professionals who might give evidence. PMID- 17355095 TI - Coroners' autopsies: quality concerns in the United Kingdom. AB - Safety in health care has increasingly become a key focus of health care providers. Data on "patient outcomes" and evidence-based clinical decision-making have led to real changes in health care policy and care provision. Specialist groups such as the National Patient Safety Agency which operates the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) in the United Kingdom are reliant on good information in order to identify factors that lead to poor patient care. In a recent study the NCEPOD reviewed the quality of coroners' autopsy reports on which they rely for much of their core data. The study found that just over half of the reports (52%) were considered satisfactory by the reviewers, 19% were good and 4% were excellent. However, over a quarter of autopsies were marked as poor or of an unacceptable standard. While analysing the factors associated with poor-quality autopsies, comments and recommendations were made with regard to the processes of death investigation and the degree to which the coroner's death investigation meets the needs of health care services. PMID- 17355096 TI - In vitro fertilisation and the limits of consent. AB - In Evans v United Kingdom (2006) 43 EHRR 21; [2006] ECHR 200 the European Court of Human Rights was asked to overrule domestic legislation in the United Kingdom which stipulated that either the male or female provider of gametes could withdraw their consent to proceed at any time prior to implantation of embryos. The court held by a majority of five to two that such a legislative regime is compatible with current human rights instruments applicable in Europe. Ms Evans has appealed the European Court's decision to the Grand Chamber. However, compelling public policy arguments suggest that both parties to proposed in vitro fertilisation treatment should be permitted to withdraw their consent until the point of implantation. PMID- 17355097 TI - Towards a better consent form. AB - The medical profession is in the habit of using a standard "consent form" to record a patient's consent to medical therapy, particularly for a surgical operation. This article explores how to design a consent form to avoid the many traps to be found in the law of consent. PMID- 17355098 TI - Commercialisation of regenerative human tissue: regulation and reform in Australia and England, Wales and Northern Ireland. AB - The commercialisation of therapeutic products containing regenerative human tissue is regulated by the common law, statute and ethical guidelines in Australia and England, Wales and Northern Ireland. This article examines the regulatory regimes in these jurisdictions and considers whether reform is required to both support scientific research and ensure conformity with modern social views on medical research and the use of human tissue. The authors consider the crucial role of informed consent in striking the balance between the interests of researchers and the interests of the public. PMID- 17355099 TI - Public education and organ donation: untested assumptions and unexpected consequences. AB - While the number of individuals able to benefit from transplantation increases with technological developments, donation rates remain insufficient to cater for demand. A universal response to the insufficient number of donor organs has been public education to increase knowledge about donation and transplantation, and to encourage individuals to register their wishes about donation. Although education appears to have increased knowledge and encouraged individuals to register their wishes, it has not increased the number of organs available for transplantation. In fact, there is some evidence that encouraging people to register their wishes may be detrimental to increasing net donation rates. The failure of education programs to increase organ donation rates may be due in part to a failure to recognise that attitudes to donation are influenced by complex socio-cultural and personal beliefs, and not simply by knowledge. Research aiming to increase the rate at which organs are procured for donation must recognise that some individuals do not support transplantation and have their own personal reasons for maintaining this position. Educational interventions should not assume that increasing knowledge or simply encouraging individuals to declare a decision about donation will increase consent to donation. PMID- 17355100 TI - Investigating genetic discrimination in the Australian life insurance sector: the use of genetic test results in underwriting, 1999-2003. AB - A major component of the Genetic Discrimination Project (GDP), an Australia-wide study to examine the advantages and disadvantages for individuals of having genetic information and cases of alleged genetic discrimination, is the analysis of insurers' use of genetic test results. The peak life insurance body, IFSA, had collected data through the Australian Institute of Actuaries (AIA) for the period June 1999-May 2003 from life insurance companies in Australia regarding their use of genetic test results in insurance underwriting. The GDP negotiated with IFSA and the AIA for access to this data for independent analysis. Applications from 288 individuals who had disclosed a genetic test result included products for cover for death, trauma/crisis, income protection/disability and total and permanent disablement. A total of 81% (234/288) contained usable data for analysis. These cases involved the genetic conditions haemochromatosis (71%), Huntington disease (12%) and breast/ovarian cancer (6%). In 49% of cases, the genetic test result was described as the only influencing factor and of these, 32% involved a "positive" genetic test result. Whilst underwriting in most cases appeared to be reasonable, the article highlights several cases involving disclosure of a positive predictive test result for breast/ovarian cancer that required further investigation. PMID- 17355101 TI - Pharmacy practice developments: the potential impact on pharmacists' legal liability. AB - The practice of pharmacy has changed over recent years with a greater emphasis on the patient and the provision of patient care services. This expanded role of pharmacists as medication managers has resulted in changes to their professional responsibility and potential legal liability. Recent international case law demonstrates an increased legal liability of pharmacists in certain instances. However, pharmacists' liability in this new context in Australia is yet to be clarified. PMID- 17355102 TI - Capacity and medical self-determination in Australia. AB - The expansion of patients' rights and the increasing complexity of the science of medicine raises serious legal and social questions, particularly when they pertain to end-of-life decision-making. Medical science continues to find ways of maintaining or extending life in a body or mind affected by disease or trauma and regular advances in medical technology and practice mean that the natural course of illness or injury will rarely be uninterrupted by some form of medical intervention. This progressive "medicalisation" of death, together with enhanced patient autonomy, means that choices can increasingly be made regarding medical treatment which may ultimately influence both the time and the way in which a person dies. This article examines both legislation and the common law in Australia particularly as it pertains to medical decision-making at end-of-life and the patient's right of self-determination. PMID- 17355103 TI - Mainstream medicine versus complementary and alternative medicine in the witness box: resolving the clash of ideologies. AB - Mainstream medical philosophy and practice differ in many respects from those of complementary and alternative medicine (CAM), differences which are explored in this article. Because of a resurgence of CAM therapies, courts and tribunals will scrutinise CAM in more and more contexts in the future. Such court cases may require the resolution of conflicts between opinions of CAM and medical experts. This article considers how courts evaluate such opinions where experts hold conflicting ideologies or philosophical approaches, and addresses the following questions: Do the opinions of CAM practitioners qualify as "expert" opinions in court? How do the courts examine the basis of such opinions? Are they systematically given less weight than the opinions of mainstream medical practitioners? Will recent procedural reforms for hearing expert evidence make it easier for courts to resolve these issues? PMID- 17355104 TI - Chemotherapy dosing part II: alternative approaches and future prospects. AB - This overview follows on from part I, which described the current practices used in chemotherapy dosing and the paucity of scientific evidence to support them. In part II, alternative approaches are discussed, both in terms of scientific rationale and practical application. These include therapeutic drug monitoring, the use of pharmacokinetic-pharmacodynamic relationships, flat-fixed dosing, Bayesian modelling and dose banding. PMID- 17355105 TI - Ifosfamide encephalopathy. AB - Encephalopathy is a potentially fatal toxicity of ifosfamide. Clinical manifestations of encephalopathy range from fatigue and confusion to coma and death. Early identification of this toxicity and prompt cessation of ifosfamide are the essential elements in the management of ifosfamide encephalopathy. Accurate prediction of this toxicity is often difficult. Based on the limited available evidence, methylene blue, an electron acceptor, may have a role in the treatment and the prevention of neurotoxicity. This paper reviews the current understanding of ifosfamide encephalopathy. PMID- 17355106 TI - Variability in radiation oncologists' opinion on the indication of a bolus in post-mastectomy radiotherapy: an international survey. AB - AIMS: Post-mastectomy radiotherapy (PMRT) decreases locoregional recurrence and increases survival for women with large tumours and/or node-positive disease. The American Society of Clinical Oncology has published treatment guidelines, but has also indicated that the optimal technique for PMRT remains unknown. The objective of this study was to evaluate the variability in which a bolus is currently used in PMRT and to identify the clinical situations in which a bolus is used. MATERIALS AND METHODS: In 2004, an e-mail survey was sent to all active physician members of the American Society for Therapeutic Radiology and Oncology, the Canadian Association of Radiation Oncologists and the European Society for Therapeutic Radiology and Oncology. The survey focused on the technical details regarding the use of a bolus in PMRT. RESULTS: In total, 1035 responses were obtained: 642 from the Americas (568 from the USA), 327 from Europe and 66 from Australasia. Respondents from the Americas were significantly more likely to always use a bolus (82%) than the Europeans (31%), as were the Australasians (65%) (P < 0.0001). Europeans were significantly more likely to use a bolus for specific indications (P < 0.0001). The results also showed wide variation in the schedule of application (every day [33%] and alternate days [46%]) and thickness used (< 1 cm [35%] and > or = 1 cm [48%]). CONCLUSIONS: There is a wide variation in the use of a bolus in PMRT with significant regional differences. This probably translates into a variation in the dose delivered to the skin and may have an effect on local recurrence and/or toxicity. A randomised clinical trial is needed to evaluate the benefit and toxicity associated with the use of a bolus in PMRT. PMID- 17355107 TI - Adjuvant hypofractionated radiation therapy for breast cancer after conserving surgery. AB - AIMS: To evaluate the incidence of locoregional recurrence (LRR) and the cosmetic results in a group of patients with breast cancer treated with a hypofractionated schedule of adjuvant radiotherapy after conservative surgery. MATERIALS AND METHODS: In total, 539 patients with pTis-pT1-pT2 breast cancer underwent radiotherapy treatment after conservative surgery at the University of Florence and at the Pistoia Hospital. The dose delivered was 44 Gy (2.75 Gy daily fraction). The tumour bed boost (10 Gy) was given by electrons. RESULTS: At the time of the analysis, 1.8% of patients (10/539) had breast relapse. No patients developed nodal recurrence (supraclavicular, axillary and internal mammary nodes). The 3- and 5-year actuarial rates for LRR were 1.2% (+/- 0.5% standard error) and 2.1% (+/- 0.6% standard error), respectively. Considering the late toxicity, we found that 412 (76.4%) patients had grade 0 or grade 1 late toxicity, 113 patients (20.9%) had grade 2 late toxicity and 14 patients (2.5%) had grade 3 late toxicity. No patients developed grade 4 toxicity. CONCLUSION: This type of approach resulted in an effective treatment in terms of local control in patients with negative or one to three positive axillary nodes and negative surgical margins. Patients treated with a hypofractionated schedule showed very good cosmesis. PMID- 17355108 TI - The neoadjuvant approach in the treatment of patients with advanced epithelial ovarian carcinoma. AB - AIMS: Ovarian cancer has a very poor prognosis, with 5-year survival rates of 5 20% for advanced-stage disease. This work was designed to verify whether the neoadjuvant approach had an effect on survival in patients with advanced-stage ovarian cancer. MATERIALS AND METHODS: Patients with stage III or IV disease who received neoadjuvant platinum-based chemotherapy (group 1) were compared with a group of conventionally treated patients (group 2). RESULTS: Most of the patients in group 1 (76%) had partial tumoral responses after chemotherapy. Patients from group 1 (n = 42) had a median survival that was not different from that in patients from group 2 (n = 348). Patients who received platinum-based chemotherapy with taxanes had the same survival of patients who received no taxanes. CONCLUSIONS: Our results showed similar responses and survival rates for patients with stage III or IV ovarian cancer treated with neoadjuvant platinum based chemotherapy, when compared with patients who underwent primary suboptimal cytoreductive surgery. Our data therefore support the ongoing trials to determine the optimum timing of surgery for ovarian cancer. PMID- 17355109 TI - Modern chemotherapy management of recurrent ovarian cancer: a multicentre study. AB - AIMS: The natural history of ovarian cancer has changed over the last 10 years due to more effective drug treatments. The aim of this multicentre audit of the management of recurrent ovarian cancer was to examine the usage of newer drugs in light of the publication of National Institute of Clinical Excellence guidance. MATERIALS AND METHODS: All patients presenting with a first or subsequent relapse of ovarian cancer between August 2001 and February 2003 in nine UK National Health Service centres were identified. Data were recorded retrospectively and prospectively from point of entry into the study and included the modality of primary cancer treatment, the treatment of each subsequent relapse and outcome. RESULTS: In total, 245 evaluable patients were entered on to the database. The mean age was 62 years. All patients received a platinum-based chemotherapy regimen as first-line treatment. One hundred and fifty-five patients (63%) went on to receive third-line chemotherapy and 82 (34%) received fourth-line chemotherapy. The median survival from first relapse was estimated to be in excess of 12 months from our data. The efficacies of the chemotherapy agents used are comparable with the results of published phase III trials. CONCLUSION: This study shows that multicentre audit is feasible and provides useful information on current clinical practice on which to base future research. PMID- 17355110 TI - Challenges in treating patients with Down's syndrome and testicular cancer with chemotherapy and radiotherapy: The Royal Marsden experience. AB - AIMS: With a life expectancy similar to the general population, greater numbers of patients with Down's syndrome are being diagnosed with testicular cancer. Learning difficulties and medical co-morbidity are common in this patient population and may lead to non-standard oncological treatment. We aimed to identify and discuss management challenges in the treatment of these patients with chemotherapy and radiotherapy and report their clinical outcome. MATERIALS AND METHODS: The Royal Marsden Hospital urology database was searched from 1982 to 2005 to identify all cases of patients with Down's syndrome and histologically confirmed testicular cancer who were referred for consideration of chemotherapy or radiotherapy. RESULTS: Nine patients were identified, of whom eight received chemotherapy or radiotherapy. Two patients had bilateral tumours and four had crypto-orchidism. At the time of diagnosis, the patients were 21-50 years of age. Of the 11 tumours identified, nine were seminomas and two were malignant teratoma undifferentiated. Five patients presented with stage I disease, of whom three received carboplatin and one received para-aortic radiotherapy as adjuvant treatment. Three patients presented with stage II disease, of whom two were treated with carboplatin and one received combination chemotherapy followed by radiotherapy. One patient with stage IV disease was treated with carboplatin. Five of nine patients relapsed within 30 months, of whom three were successfully salvaged with radiotherapy and one with combination chemotherapy. CONCLUSION: After standard and non-standard therapy for seminoma, the relapse rate for patients in our cohort was high. Since relapsed disease is much more difficult to manage with combination chemotherapy on account of respiratory, cardiac and renal co-morbidity, adequate initial treatment is advised. Consideration of psycho social issues and the multiple treatment strategies available is vital in delivering optimal care to patients with Down's syndrome and testicular cancer. PMID- 17355111 TI - Chemotherapy in small bowel adenocarcinoma: 10-year experience of the British Columbia Cancer Agency. AB - AIMS: Small bowel adenocarcinoma (SBA) is a rare, frequently lethal, malignancy. Little is known about the use and value of chemotherapy in patients with SBA. We assessed this issue in a consecutive cohort of patients from British Columbia, Canada. MATERIALS AND METHODS: Consecutive patients with SBA seen at the British Columbia Cancer Agency from January 1990 to September 2000 were identified. A retrospective systematic chart review was undertaken and a survival analysis conducted. RESULTS: Forty-eight SBA were identified in 47 subjects. Chemotherapy was given to 21 of the 47 subjects (45%). Of 19 patients treated initially with curative intent, the median overall survival was 38.6 months. Five received adjuvant chemotherapy, with two subsequently recurring. Thirty-seven patients initially or eventually had advanced disease: 16 received 22 palliative intent fluoropyrimidine-based regimens. Only one partial response was seen in the first line (objective response rate 6%). The median overall survival for those who received palliative chemotherapy was 15.6 months compared with 7.7 months for those who did not. CONCLUSIONS: Chemotherapy use is common in SBA. Our data and available published studies suggest that chemotherapy may provide benefit, but the optimal chemotherapy regimen and the degree of benefit remain to be defined. A sound approach to investigate the management of rare malignancies is desperately needed. PMID- 17355112 TI - 13-cis-Retinoic acid in combination with gemcitabine in the treatment of locally advanced and metastatic pancreatic cancer--report of a pilot phase II study. AB - AIMS: Adenocarcinoma of the pancreas is a cancer with extremely poor prognosis and limited therapeutic options. Retinoids are derivatives of vitamin A involved in the control of many biological functions, including cell growth and differentiation and the induction of apoptosis. On the basis of pre-clinical evidence and some clinical data, we conducted a phase II study of 13-cis-retinoic acid (13-cis-RA) in combination with gemcitabine in patients with unresectable pancreatic carcinoma. MATERIALS AND METHODS: Patients with histologically confirmed unresectable pancreatic carcinoma were treated with gemcitabine 1000 mg/m2 on days 8, 15, 22 plus 13-cis-RA 1 mg/kg on days 1-14 for six cycles. The end points included the objective response rate and median survival. RESULTS: Thirty patients were recruited, 15 men and 15 women; 20 patients were evaluable. The median age was 65 years (range 44-79 years) and the median Karnofsky performance status was 80% (range 60-100%). The median follow-up was 21 months. One patient achieved a partial remission, seven patients had stable disease and 12 patients developed progressive disease. Toxicity was mainly haematological, with eight cases of grade 3 and four cases of grade 4 neutropenia, thrombocytopenia and anaemia. The median survival was 7.8 months (range 2.6-21.6 months). CONCLUSIONS: The combination of gemcitabine and 13-cis-RA was well tolerated, but we did not see improvement in the response rate. Further studies with other retinoids may be beneficial to patients with unresectable pancreatic cancer. PMID- 17355113 TI - The transcription factor nuclear factor-kappa B and cancer. AB - Since the discovery of nuclear factor-kappa B (NF-kappaB) in 1986, many studies have been conducted showing the link between the NF-kappaB signalling pathway and control of the inflammatory response. Today it is well known that control of the inflammatory response and apoptosis is closely related to the activation of NF kappaB. Three NF-kappaB activation pathways exist. The first (the classical pathway) is normally triggered in response to microbial and viral infections or exposure to pro-inflammatory cytokines that activate the tripartite IKK complex, leading to phosphorylation-induced IkappaB degradation and depends mainly on IKKbeta activity. The second (the alternative pathway), leads to selective activation of p52:RelB dimers by inducing the processing of the NF-kappaB2/p100 precursor protein, which mostly occurs as a heterodimer with RelB in the cytoplasm. This pathway is triggered by certain members of the tumour necrosis factor cytokine family, through selective activation of IKKalpha homodimers by the upstream kinase NIK. The third pathway is named CK2 and is IKK independent. NF-kappaB acts through the transcription of anti-apoptotic proteins, leading to increased proliferation of cells and tumour growth. It is also known that some drugs act directly in the inhibition of NF-kappaB, thus producing regulation of apoptosis; some examples are aspirin and corticosteroids. Here we review the role of NF-kappaB in the control of apoptosis, its link to oncogenesis, the evidence of several studies that show that NF-kappaB activation is closely related to different cancers, and finally the potential target of NF-kappaB as cancer therapy. PMID- 17355114 TI - Utility of regular serum biochemistry and midstream urine cultures in men undergoing three-dimensional conformal pelvic radiotherapy for prostate cancer. PMID- 17355115 TI - Post-transplant lymphoproliferative disorder (PTLD). PMID- 17355116 TI - Metastasectomy plus immunotherapy compared with immunotherapy alone in metastatic renal cell carcinoma. PMID- 17355117 TI - Covalent 2D and 3D networks from 1D nanostructures: designing new materials. AB - We show extensive theoretical studies related to the generation and characterization of 2D and 3D ordered networks using 1D units that are connected covalently. We experimentally created multi-terminal junctions containing 1D carbon blocks in order to study the most common morphologies and branched structures that could be used in the theoretical design of network models. We found that the mechanical and electronic characteristics of ordered networks based on carbon nanotubes (ON-CNTs) are dominated by their specific super architecture (hexagonal, cubic, square, and diamond-type). We show that charges follow specific paths through the nodes of the multi-terminal systems, which could result in complex integrated nanoelectronic circuits. The 3D architectures reveal their ability to support extremely high unidirectional stress when their mechanical properties are studied. In addition, these networks are shown to perform better than standard carbon aerogels because of their low mass densities, continuous porosities, and high surface areas. PMID- 17355118 TI - Synthesis and assessment of first-generation polyamidoamine dendrimer prodrugs to enhance the cellular permeability of P-gp substrates. AB - The aim of this study is to evaluate the potential use of first-generation (G1) polyamidoamine (PAMAM) dendrimers as drug carriers to enhance the permeability, hence oral absorption, of drugs that are substrates for P-glycoprotein (P-gp) efflux transporters. G1 PAMAM dendrimer-based prodrugs of the water-insoluble P gp substrate terfenadine (Ter) were synthesized using succinic acid (suc) or succinyl-diethylene glycol (suc-deg) as a linker/spacer (to yield G1-suc-Ter and G1-suc-deg-Ter, respectively). In addition, the permeability of G1-suc-deg-Ter was enhanced by attaching two lauroyl chains (L) to the dendrimer surface (L2-G1 suc-deg-Ter). All of the G1 dendrimer-terfenadine prodrugs were more hydrophilic than the parent drug, as evaluated by drug partitioning between 1-octanol and phosphate buffer at pH 7.4 (log K(app)). The influence of the dendrimer prodrugs on the integrity and viability of human Caucasian colon adenocarcinoma cells (Caco-2) was determined by measuring the transepithelial electrical resistance (TEER) and leakage of lactate dehydrogenase (LDH) enzyme, respectively. The LDH assay indicated that the dendrimer prodrugs had no impact on the viability of Caco-2 cells up to a concentration of 1 mM. However, the IC(50) of the prodrugs was lower than that of G1 PAMAM dendrimer because of the high toxicity of terfenadine. Measurements of the transport of dendrimer prodrugs across monolayers of Caco-2 cells showed an increase of the apparent permeability coefficient (P(app)) of terfenadine in both apical-to-basolateral (A --> B) and basolateral-to-apical (B --> A) directions after its conjugation to G1 PAMAM dendrimer. The A --> B P(app) of the dendrimer prodrugs was significantly greater than B --> A P(app). The surface-modified dendrimer prodrug L2-G1-suc-deg-Ter showed the highest A --> B permeability among the conjugates. PMID- 17355119 TI - Rheology of sodium hyaluronate saline solutions for ophthalmic use. AB - The aim of this work was to investigate the rheological properties of different saline solutions of sodium hyaluronate (NaHA) with special interest for medical applications. The experimental results were compared with literature data for commercial ophthalmic viscosurgical devices (OVDs) used in cataract surgery. We offer some tools to tailor the rheological behavior of OVDs for different purposes. We have investigated to which extent surgical requirements can be fulfilled by adjusting either the molecular weight of NaHA or its concentration, parameters that are in some respects equivalent but not in others. Furthermore, we demonstrate that moduli and complex viscosities of NaHA saline solutions are adequately falling on master curves, using either empirical or calculated shift factors, the latest ones being based on a modified Rouse model. PMID- 17355120 TI - Does water activity rule P. mirabilis periodic swarming? I. Biochemical and functional properties of the extracellular matrix. AB - The dynamics of bacterial colonies is complex in nature because it correlates the behavior of numerous individual cells in space and time and is characterized by emergent properties such as virulence or antibiotics resistance. Because there is no clear-cut evidence that periodic swarming of P. mirabilis colonies is ruled by chemical triggers responsible for cell-to-cell signaling in most of the biofilms, we propose that the observed periodicity relies on the colony's global properties. Hence, the biochemical and functional properties of the extracellular matrix (ECM) of P. mirabilis colonies were investigated. A binary exopolysaccharide mixture (1 and 300 kDa), glycinebetaine, and a phenoglycolipid were identified. Rheology, calorimetry, and water sorption experiments performed on purified EPS bring evidence that these exoproducts exhibit marked viscoelasticity, which likely relies on large scale H bond networks. Such behavior is discussed in terms of water activity because the mechanical ECM properties were found to depend on hydration. PMID- 17355121 TI - Does water activity rule P. mirabilis periodic swarming? II. Viscoelasticity and water balance during swarming. AB - Following the analysis of the biochemical and functional properties of the P. mirabilis extra cellular matrix performed in the first part of this study, the viscoelasticity of an actively growing colony was investigated in relation to water activity. The results demonstrate that the P. mirabilis colony exhibits a marked viscoelastic character likely due to both cell rafts and exoproduct H-bond networks. Besides, the water loss by evaporation during migration has been measured, whereas the experimental determination of the water diffusion coefficient in agar has allowed us to estimate the net water influx at the agar/colony interface. These data drive us to propose that a periodic increase of the water activity at the colony's periphery, mainly due to the drastic surface to volume ratio increase associated with swarming, causes the periodic and synchronous cessation of migration through the dissociation of exoproduct networks, which in turn strongly alters the matrix viscoelasticity. PMID- 17355122 TI - Mechanism of the severe inhibition of tetrachlorohydroquinone dehalogenase by its aromatic substrates. AB - Tetrachlorohydroquinone (TCHQ) dehalogenase catalyzes the conversion of TCHQ to 2,6-dichlorohydroquinone during degradation of pentachlorophenol by Sphingobium chlorophenolicum. TCHQ dehalogenase is a member of the glutathione S-transferase superfamily. Members of this superfamily typically catalyze nucleophilic attack of glutathione upon an electrophilic substrate to form a glutathione conjugate and contain a single glutathione binding site in each monomer of the typically dimeric enzyme. TCHQ dehalogenase, in contrast to most members of the superfamily, is a monomer and uses 2 equiv of glutathione to catalyze a more complex reaction. The first glutathione is involved in formation of a glutathione conjugate, while the second is involved in the final step of the reaction, a thiol-disulfide exchange reaction that regenerates the free enzyme and forms GSSG. TCHQ dehalogenase is severely inhibited by its aromatic substrates, TCHQ and trichlorohydroquinone (TriCHQ). TriCHQ acts as a noncompetitive inhibitor of the thiol-disulfide exchange reaction required to regenerate the free form of the enzyme. In addition, dissociation of the GSSG product is inhibited by TriCHQ. The thiol-disulfide exchange reaction is the rate-limiting step in the reductive dehalogenation reaction under physiological conditions. PMID- 17355123 TI - Characterization of DNA--protein cross-links induced by oxanine: cellular damage derived from nitric oxide and nitrous acid. AB - Reactive nitrogen species are implicated in inflammatory diseases and cancers. Oxanine (Oxa) is a DNA lesion derived from the guanine base with nitric oxide, nitrous acid, or N-nitrosoindoles. It was shown by gel electrophoresis that oxanine mediated the formation of DNA-protein cross-links (DPCs) with DNA-binding proteins and in the cell extract. Although 2'-deoxyoxanosine was shown to react with amines including the N-terminal amino group of glycine, the structures of DNA-protein cross-links induced by oxanine have not been characterized. In this study, we find that the thiol group of the amino acid side chain is reactive toward oxanine, forming a thioester. Two reaction products of oxanine, namely, the thioester and the amide adducts, with the endogenous tripeptide glutathione (GSH) as a model protein were characterized on the basis of their UV, NMR (1H- and 13C-), and mass spectra. Interestingly, the disulfide GSSG also reacts with oxanine, forming the thioester adduct. The thioester and the amide adducts are generated when GSH and GSSG react with oxanine-containing calf thymus DNA, and they might be possible forms of cellular DPCs. Because the repair mechanism of DPCs is not extensively investigated, the characterization of oxanine-derived DPC structures should shed light on their detection in vivo and on their biological consequences. PMID- 17355124 TI - Structure-function analysis of glutamine synthetase adenylyltransferase (ATase, EC 2.7.7.49) of Escherichia coli. AB - Glutamine synthetase adenylyltransferase (ATase) regulates the activity of glutamine synthetase by adenylylation and deadenylylation in response to signals of nitrogen and carbon status: glutamine, alpha-ketoglutarate, and the uridylylated and unmodified forms of the PII signal transduction protein. ATase consists of two conserved nucleotidyltransferase (NT) domains linked by a central region of approximately 200 amino acids. Here, we study the activities and regulation of mutated and truncated forms of ATase. Our results indicate the following. (i) The N-terminal NT domain contained the adenylyl-removing (AR) active site, and the C-terminal NT domain contained the adenylyltransferase (AT) active site. (ii) The enzyme contained a glutamine binding site, and glutamine increased the affinity for PII. (iii) The enzyme appeared to contain multiple sites for the binding of PII and PII-UMP. (iv) Truncated versions of ATase missing the C-terminal (NT) domain lacked both AT and AR activity, suggesting a role for the C-terminal NT domain in both activities. (v) The purified C-terminal NT domain and larger polypeptides containing this domain had significant basal AT activity, which was stimulated by glutamine. These polypeptides were indifferent to PII and PII-UMP, or their ATase activity was inhibited by either PII or PII UMP. (vi) Certain point mutations in the central region or an internal deletion removing most of this part of the protein eliminated the AR activity and eliminated activation of the AT activity by PII, while not eliminating the binding of PII or PII-UMP. That is, these mutations in the central region appeared to destroy the communication between the PII and PII-UMP binding sites and the AT and AR active sites. (vii) Certain mutations in the central region of ATase appeared to dramatically improve the binding of glutamine to the enzyme. (viii) While the isolated AT and AR domains of ATase bound poorly to PII and PII UMP, these domains bound PII and PII-UMP significantly better when linked to the central region of ATase. Together, our results indicate a highly coordinated enzyme, in which the AT and AR domains participate in each other's regulation and distant regulatory sites are in communication with each other. A model for the regulation of ATase by glutamine, PII, and PII-UMP consistent with all data is presented. PMID- 17355125 TI - Escherichia coli glutamine synthetase adenylyltransferase (ATase, EC 2.7.7.49): kinetic characterization of regulation by PII, PII-UMP, glutamine, and alpha ketoglutarate. AB - Glutamine synthetase adenylyltranferase (ATase, EC 2.7.7.49) catalyzes the adenylylation and deadenylylation of glutamine synthetase (GS), regulating GS activity. The adenylyltransferase (AT) reaction is activated by glutamine and by the unmodified form of the PII signal transduction protein and is inhibited by the uridylylated form of PII, PII-UMP. Conversely, the adenylyl-removing (AR) reaction is activated by PII-UMP and is inhibited by glutamine and by PII. Both AT and AR reactions are regulated by alpha-ketoglutarate, which binds to PII and PII-UMP. Here, we present a kinetic analysis of the AT and AR activities and their regulation. Both AT and AR reactions used a sequential mechanism of rapid equilibrium random binding of substrates and products. Activators and inhibitors had little effect on the binding of substrates, instead exerting their effects on catalysis. Our results were consistent with PII, PII-UMP, and glutamine shifting the enzyme among at least six different enzyme forms, two of which were inactive, one of which exhibited AR activity, and three of which exhibited AT activity. In addition to a site for glutamine, the enzyme appeared to contain two distinct sites for PII and PII-UMP. The PII, PII-UMP, and glutamine sites were in communication so that the apparent activation and inhibition constants for regulators depended upon each other. The binding of PII was favored by glutamine and its level reduced by PII-UMP, whereas glutamine and PII-UMP competed for the enzyme. alpha-Ketoglutarate, which acts exclusively through its binding to PII and PII-UMP, did not alter the binding of PII or PII-UMP to the enzyme. Rather, alpha-ketoglutarate dramatically affected the extent of activation or inhibition of the enzyme by PII or PII-UMP. A working hypothesis for the regulation of the AT and AR activities, consistent with all data, is presented. PMID- 17355126 TI - Molecular oxygen dependent steps in fatty acid oxidation by cyclooxygenase-1. AB - The mechanism by which cyclooxygenase-1 (COX-1), a heme- and tyrosyl radical containing enzyme, catalyzes the regio- and stereospecific oxygenation of polyunsaturated fatty acids to prostaglandin or hydroperoxide products has not been understood. Steady-state kinetic studies conducted with the native substrate arachidonic acid and the slower substrate linoleic acid are described here. Second-order rate constants, kcat/KM for fatty acid and O2, are found to depend upon the concentration of the other cosubstrate. Competitive oxygen kinetic isotope effects (18O KIEs) kcat/KM(16,16O2)/kcat/KM(18,16O2) reveal that a peroxyl radical is formed in or before the first kinetically irreversible step. Together, the results indicate that the oxygenase reaction occurs by a sequential mechanism which most likely involves reversible abstraction of a hydrogen atom from the fatty acid prior to the trapping of the delocalized substrate radical by O2. The identity of the first kinetically irreversible step, subsequent to forming the peroxyl radical, is also discussed in the context of the magnitude of the oxygen kinetic isotope effects as well as the behavior of kcat/KM(O2) in response to changing solvent pH, pD, and viscosity. PMID- 17355127 TI - High sensitivity identification of membrane proteins by MALDI TOF-MASS spectrometry using polystyrene beads. AB - Membrane proteins play a large variety of functions in life and represent 30% of all genomes sequenced. Due to their hydrophobic nature, they are tightly bound to their biological membrane, and detergents are always required to extract and isolate them before identification by mass spectrometry (MS). The latter, however remains difficult. Peptide mass fingerprinting methods using techniques such as MALDI-TOF MS, for example, have become an important analytical tool in the identification of proteins. However, PMF of membrane proteins is a real challenge for at least three reasons. First, membrane proteins are naturally present at low levels; second, most of the detergents strongly inhibit proteases and have deleterious effects on MALDI spectra; and third, despite the presence of detergent, membrane proteins are unstable and often aggregate. We took the mitochondrial uncoupling protein 1 (UCP1) as a model and showed that differential acetonitrile extraction of tryptic peptides combined with the use of polystirene Bio-Beads triggered high resolution of the MALDI-TOF identification of mitochondrial membrane proteins solubilized either with Triton-X100 or CHAPS detergents. PMID- 17355128 TI - A trinuclear copper(II) complex of 2,4,6-tris(di-2-pyridylamine)-1,3,5-triazine shows prominent DNA cleavage activity. AB - A highly water soluble 3:2 complex of copper(II) and 2,4,6-tris(di-2 pyridylamine)-1,3,5-triazine (TDAT) has been synthesized and structurally characterized. The complex crystallized in a triclinic P1 space group with a molecular formula of [Cu3(TDAT)2Cl3]Cl3.2H2O (1), where each copper ion is coordinated by four pyridine nitrogen atoms and an apical chloride. The trinuclear complex is stable at physiological relevant conditions. It can bind to DNA through electrostatic attraction and cleave efficiently the supercoiled pBR322 DNA into its nicked and linear forms at micromolar concentrations. Active oxygen intermediates such as hydroxyl radicals and singlet oxygen generated in the presence of 1 may act as active species for the DNA scission. PMID- 17355129 TI - Novel 3D LnIII-CuI supramolecular architecture based on 2D MOFs with (6,3) topology. AB - Three novel coordination polymers, [LnCu(PZDC)3].[Ln(H2O)9]0.5.[(H2O)7H+]0.5 [Ln = La (1), Eu (2), Gd (3)], were synthesized. They are the first 3d-4f heterometallic framework with supramolecular 1D channels, in which lanthanide hydrate cations and lattice water molecules are located. PMID- 17355130 TI - Calculation of water-exchange rates on aqueous polynuclear clusters and at oxide water interfaces. AB - The rates of a wide variety of reactions in aqueous coordination compounds can be correlated with lifetimes of water molecules in the inner-coordination shell of the metal. For simple octahedral metal ions, these lifetimes span approximately 1020 but are unknown, and experimentally inaccessible, for reactive sites in interfacial environments. Using recent data on nanometer-sized aqueous aluminum clusters, we show that lifetimes can be calculated from reactive-flux molecular dynamics simulations. Rates scale with the calculated metal-water bond lengths. Surprisingly, on all aluminum(III) mineral surface sites investigated, waters have lifetimes in the range of 10-8-10-10 s, making the surface sites as fast as the most reactive ions in the solution. PMID- 17355131 TI - Proton-induced cis-trans conversion of a platinum(II) center coordinated by L cysteinatocobalt(III) metalloligands. AB - Treatment of LambdaL-[Co(L-cys-N,S)(en)2]+ (l-H2cys = L-cysteine) with [PtCl4]2- in water, followed by the addition of acid, gave an S-bridged CoIII2PtII trinuclear complex ([1]4+), which was reversibly converted to its deprotonated complex ([2]2+) in an aqueous solution. While [1]4+ formed only a trans isomer, [2]2+ existed as a mixture of trans and cis isomers. The selective formation of a cis isomer was achieved by treatment of [1]4+ or [2]2+ with phthalic acid in water, which afforded a unique CoIII4PtII2 hexanuclear complex ([3]4+). Complex [3]4+ was reverted back to [1]4+ by treatment with aqueous HCl, accompanied by the complete cis-to-trans conversion. PMID- 17355132 TI - Functional polythiophene nanoparticles: size-controlled electropolymerization and ion selective response. AB - We have synthesized a thiophene derivative, (4-benzeno-15-crown-5 ether) thiophene-3-methylene-amine (BTA), which was used as a monomer for electrochemical polymerization on metallic surfaces to prepare functional polymer films. Self-assembly of BTA monomers on Au(111) surfaces promotes ordered polymerization to form polymer nanoparticles or clusters by which the size of the polymer nanoparticles can further be controlled electrochemically. The electropolymerization was monitored in situ by scanning tunneling microscopy to unravel the dynamics of the process and possible mechanisms. These are further supported by calculations using a semiquantative model of polymer clusters and X ray photoelectron spectroscopy analysis. On the basis of these observations, we have attempted to optimize the construction of BTA polymer based ion selective electrodes. The BTA based polymer films, prepared from both aqueous solution and organic phase on gold electrodes, displayed selective sensitivity to potassium ions with a linear dependence of ion concentration over 4 orders of magnitude. PMID- 17355133 TI - Total syntheses of 2,2'-epi-cytoskyrin A, rugulosin, and the alleged structure of rugulin. AB - The total syntheses of 2,2'-epi-cytoskyrin A, rugulosin, and the alleged structure of rugulin are described. These naturally occurring bisanthraquinones and their relatives are characterized by novel molecular architectures at the core, at which lies a more or less complete, cage-like structural motif termed "skyrane". The strategies developed for their total synthesis feature a cascade sequence called the "cytoskyrin cascade" and deliver these molecules in short order and in a stereoselective manner. PMID- 17355134 TI - Infrared and ultraviolet spectral signatures and conformational preferences of jet-cooled serotonin. AB - The ultraviolet and infrared spectroscopy of single conformations of neutral serotonin (5-hydroxytryptamine) have been studied in the gas phase using a combination of methods including laser-induced fluorescence, resonance-enhanced two-photon ionization, UV-UV hole-burning spectroscopy, and resonant ion-dip infrared spectroscopy. By comparison to its close analogue tryptamine, for which firm assignments to seven low-energy conformations have been made, UV and IR transitions due to eight conformations of serotonin are observed and assigned. The ultraviolet spectrum divides into two subsets of transitions separated from one another by approximately 230 cm-1 ascribable to syn and anti conformations of the 5-OH group. These two subsets are also distinguishable via their 5-OH stretch fundamentals, with the anti-OH subset shifted by approximately 4-5 cm-1 to lower frequency than those due to syn-OH conformers. The existing firm assignments for tryptamine play a decisive role in assignments in serotonin, where the alkyl CH stretch infrared spectrum is diagnostic of the conformation of the ethylamine side chain. Conformer A of serotonin (SERO(A)), with S1 <-- S0 origin transition at 32584 cm-1, is assigned to Gpy(out)/anti-OH, SERO(B) at 32548 cm-1 to Gpy(up)/anti, SERO(C) at 32545 cm-1 to Gph(out)/anti, SERO(D) at 32560 cm-1 to Anti(py)/anti, SERO(E) at 32537 cm-1 to Anti(up)/anti, SERO(F) at 32353 cm-1 to Gpy(out)/syn, SERO(G) at 32313 cm-1 to Gpy(up)/syn, and SERO(H) at 32282 cm-1 to Gph(out)/syn. The conformational preferences of serotonin differ from those of tryptamine most notably in the selective stabilization observed for the Gph(out)/anti-OH conformer SERO(C), which makes it the second-most intense transition in the ultraviolet spectrum, surpassed only by the Gpy(out)/anti-OH conformer SERO(A). PMID- 17355135 TI - Modified-RNA aptamer-based sensor for competitive impedimetric assay of neomycin B. PMID- 17355136 TI - Catalytic nitrile-alkyne cross-metathesis. PMID- 17355137 TI - Copper-catalyzed anti-hydrophosphination reaction of 1-alkynylphosphines with diphenylphosphine providing (Z)-1,2-diphosphino-1-alkenes. AB - Hydrophosphination of 1-alkynylphosphines with diphenylphosphine proceeds in an anti fashion under copper catalysis, providing an easy and efficient access to a variety of (Z)-1,2-diphosphino-1-alkenes and their sulfides. The reaction is highly chemoselective and can be performed even in an aqueous medium. The reaction is reliable enough to realize a gram-scale synthesis of (Z)-1,2 diphosphino-1-alkene. Radical reduction of the diphosphine disulfides with tris(trimethylsilyl)silane yields the parent trivalent diphosphines without suffering from the isomerization of the olefinic geometry. Enantioselective hydrogenation of (Z)-3,3-dimethyl-1,2-bis(diphenylthiophosphinyl)-1-butene followed by desulfidation leads to a new chiral bidentate phosphine ligand. PMID- 17355138 TI - Assembly and exchange of resorcinarene capsules monitored by fluorescence resonance energy transfer. PMID- 17355139 TI - Fermentation and lactic acid addition enhance iron bioavailability of maize. AB - Maize is one of the most important cereal crops for human consumption, yet it is of concern due to its low iron bioavailability. The objective of this study was to determine the effects of processing on iron bioavailability in common maize products and elucidate better processing techniques for enhancing iron bioavailability. Maize products were processed to represent different processing techniques: heating (porridge), fermentation (ogi), nixtamalization (tortillas), and decortication (arepas). Iron and phytate contents were evaluated. Iron bioavailability was assessed using the Caco-2 cell model. Phytate content of maize products was significantly reduced by decortication (25.6%, p = 0.003) and nixtamalization (15%, p = 0.03), and iron content was reduced by decortication (29.1%, p = 0.002). The relative bioavailability (RBA, compared to 100% bioavailability of porridge with FeSO4) of ogi was significantly higher than that of other products when fortified with FeSO4 (p < 0.001) or reduced iron (p < 0.001). Addition of lactic acid (6 mg/g of maize) significantly increased iron solubility and increased bioavailability by about 2-fold (p < 0.01), especially in tortillas. The consumer panel results showed that lactic acid addition does not significantly affect the organoleptic characteristics of tortillas and arepas (p = 0.166 and 0.831, respectively). The results suggest that fermentation, or the addition of small amounts of lactic acid to unfermented maize products, may significantly improve iron bioavailability. Lactic acid addition may be more feasible than the addition of highly bioavailable but expensive fortificants. This approach may be a novel means to increase the iron bioavailability of maize products to reduce the incidence of iron deficiency anemia. PMID- 17355140 TI - Using ATR-FTIR spectroscopy to design active antimicrobial food packaging structures based on high molecular weight chitosan polysaccharide. AB - ATR-FTIR spectroscopy has been used in this study to characterize the molecular mechanisms and kinetic processes that take place when a chitosonium acetate thin coating is put in contact with water solutions, Staphylococcus aureus solutions, microbial nutrient solutions, and with a high water activity TSA hydrogel medium to simulate the effect of direct contact with high moisture foods such as fresh meats, fish, and seafood products or beverages. The results of this work suggest that the biocide carboxylate groups that form when chitosan is cast from acetic acid solutions are being continuously evaporated from the formed film in the form of acetic acid (mechanism I) in the presence of environmental humidity, rendering weak biocide film systems. On the other hand, upon direct contact of the cast chitosonium acetate film with liquid water, water solutions, or the high moisture TSA hydrogel, a positive rapid migration, with a diffusion coefficient faster than 3.7 x 10(-12) m2/s, of protonated glucosamine water soluble molecular fractions (mechanism II) takes place from the film into the liquid phase, yielding strong antimicrobial performance and leaving in the remaining cast film only the non-water soluble chitosan fractions. Finally, this study describes a refined spectroscopic methodology to predict the antimicrobial properties of chitosan and gives insight into the capacity of chitosan as a natural biocide agent. PMID- 17355141 TI - Quantitation of silibinin, a putative cancer chemopreventive agent derived from milk thistle (Silybum marianum), in human plasma by high-performance liquid chromatography and identification of possible metabolites. AB - Silibinin has recently received attention as a potential cancer chemopreventive agent because of its antiproliferative and anticarcinogenic effects. A simple and specific reversed-phase high-performance liquid chromatography method was developed and validated for the quantitation of silibinin in human plasma. Sample preparation involved simple protein precipitation, and separation was achieved on a Waters Atlantis C18 column with flow rate of 1.0 mL/min at 40 degrees C and UV detection at 290 nm. Silibinin was detected as two peaks corresponding to trans diastereoisomers. The peak area was linear over the investigated concentration range (0-5000 ng/mL). The limits of detection were 2 and 1 ng/mL for the two diastereoisomers (d1 and d2), with a recovery of 53-58%. This method was utilized to detect silibinin in plasma of colorectal patients after 7 days of treatment with silipide (silibinin formulated with phosphatidyl choline). PMID- 17355142 TI - Characterization of aroma compounds in apple cider using solvent-assisted flavor evaporation and headspace solid-phase microextraction. AB - The aroma-active compounds in two apple ciders were identified using gas chromatography-olfactometry (GC-O) and GC-mass spectrometry (MS) techniques. The volatile compounds were extracted using solvent-assisted flavor evaporation (SAFE) and headspace solid-phase microextraction (HS-SPME). On the basis of odor intensity, the most important aroma compounds in the two apple cider samples were 2-phenylethanol, butanoic acid, octanoic acid, 2-methylbutanoic acid, 2 phenylethyl acetate, ethyl 2-methylbutanoate, ethyl butanoate, ethyl hexanoate, 4 ethylguaiacol, eugenol, and 4-vinylphenol. Sulfur-containing compounds, terpene derivatives, and lactones were also detected in ciders. Although most of the aroma compounds were common in both ciders, the aroma intensities were different. Comparison of extraction techniques showed that the SAFE technique had a higher recovery for acids and hydroxy-containing compounds, whereas the HS-SPME technique had a higher recovery for esters and highly volatile compounds. PMID- 17355143 TI - Stereochemical course of tryptophan dehydrogenation during biosynthesis of the calcium-dependent lipopeptide antibiotics. AB - [reaction: see text] Hydrogen atoms are abstracted from the C2' and C3'-pro-S positions of an (S)-tryptophanyl precursor, with overall syn stereochemistry, during the biosynthesis of the C-terminal Z-2',3'-dehydrotryptophan residue of the calcium-dependent lipopeptide antibiotics (CDAs) in Streptomyces coelicolor. The absence of beta-hydroxytryptophanyl, or other possible intermediates, further suggests a direct dehydrogenation mechanism similar to that proposed for the l tryptophan 2',3'-oxidase from Chromobacterium violaceum. PMID- 17355144 TI - Blue-colored donor-acceptor [2]rotaxane. AB - [reaction: see text] A guest molecule-a bis-N-tetraethyleneglycol-substituted 3,3'-difluorobenzidine derivative-has been synthesized, and its complexation with the host, cyclobis(paraquat-p-phenylene), has been investigated. This host-guest complex was then employed in the template-directed synthesis of a blue-colored [2]rotaxane. The color of this [2]rotaxane arises from the charge-transfer absorption band between the HOMO of the guest and the LUMO of the host. This host guest complex, and the derived [2]rotaxane, completes the donor-acceptor-based RGB (red/green/blue) color complex set. PMID- 17355145 TI - An efficient and stereoselective synthesis of the monomeric counterpart of marinomycin A. AB - [structure: see text] The monomeric counterpart of marinomycin A, an antitumor antibiotic marine natural product, was synthesized efficiently in 11 steps from the commercially available ethyl (R)-(-)-3-hydroxybutyrate. The strategy was highlighted by a crucial regio- and stereoselective cross-metathesis to form the C20-C21 double bond, enantioselective allyltitanations to control the configuration of the C17, C23, and C25 stereogenic centers, and a stereocontrolled construction of the tetraene moiety based on an original Horner Wadsworth-Emmons olefination followed by a Pd-catalyzed cross-coupling. PMID- 17355146 TI - A general synthesis of substituted formylpyrroles from ketones and 4 formyloxazole. AB - A novel two-step synthesis of substituted 2-formylpyrroles is described. Aldol adducts of ketones and 4-formyloxazole undergo a dehydration/oxazole hydrolysis/cyclization cascade on sequential treatment with MsCl/Et3N and aqueous NaOH to yield 5-substituted and 4,5-disubstituted 2-formylpyrroles. The methodology was extended to an N-benzyl thiazolium salt. PMID- 17355148 TI - Total synthesis of borrelidin. AB - The total synthesis of borrelidin has been achieved. The best feature of our synthetic route is macrocyclization at C11-C12 for the construction of an 18 membered ring after esterification between two segments. A detailed examination of the macrocyclization led us to the samarium(II) iodide-mediated intramolecular Reformatsky-type reaction as the most efficient synthetic approach. The two key segments were synthesized through regioselective methylation, directed hydrogenation, stereoselective Reformatsky-type reaction, and MgBr2.Et2O-mediated chelation-controlled allylation. PMID- 17355149 TI - Synthesis, structure, and transannular pi-pi interaction of multilayered [3.3]metacyclophanes. AB - The synthesis of a series of three- to six-layered [3.3]metacyclophanes ([3.3]MCPs) 3-6 has been successfully accomplished by the (p-tolylsulfonyl)methyl isocyanide (TosMIC) method as a critical coupling reaction. Their important synthetic intermediates are the two- and three-layered bis(bromomethyl) compounds 11, 17, 21, and tetrakis(bromomethyl) compounds 25 and 28. The structures of the three- to six-layered [3.3]MCPs (3-6) as well as three- to six-layered [3.3]MCP di- (22-24) and tetraones (26, 27, and 29) as the synthetic intermediates have been elucidated based on the 1H NMR data and X-ray structural analysis. These multilayered cyclophanes are constructed with two different geometries, syn [3.3]MCP and anti-[3.3]MCP-2,11-dione. In principle, their geometries are maintained in the multilayered [3.3]MCPs, but deformation of the dihedral angle of the two benzene rings of the syn-[3.3]MCP moiety is generally observed. In the four-layered MCP 4, the central [3.3]MCP moiety takes an anti geometry. These data indicate the structural flexibility of the [3.3]MCP moiety. In the electronic spectra, rather simple and structureless absorption curves are observed, and the most significant spectral change is observed for the two to three layers and becomes less effective even if it is more layered. In the charge transfer (CT) bands of the multilayered [3.3]MCPs with tetracyanoethylene (TCNE), the lambdamax gradually shifts to the longer wavelength region, but the extent of the shift is much smaller as the number of layers increases. In the multilayered [3.3]MCP-di- and tetraones, the anti-[3.3]MCP-dione moiety works as an insulator. Therefore, the CT interaction of the four- and five-layered [3.3]MCPs with one anti-[3.3]MCP-dione moiety (23 and 24) shows the almost comparable magnitude of the interaction with the two- and three-layered [3.3]MCPs (2 and 3), respectively. The tetraones of the three and four-layered MCPs (29 and 26) do not show CT interactions except for the six-layered MCP 27. PMID- 17355150 TI - An azomethine ylide approach to complex alkaloid-like heterocycles. AB - The nitrone above is readily available via the intramolecular aza Diels-Alder reaction of an amino acid derived triene in acetic acid. Subsequent treatment of the nitrone in refluxing toluene with substituted actetylenes produced the pictured pyrrole. At lower temperatures a 2,3-dihydroisoxazole, which is the product of a 3+2 dipolar cycloaddition, is produced. Upon heating in refluxing toluene the 2,3-dihydroisoxazole is converted to the pyrrole. PMID- 17355151 TI - Total synthesis and bioactivity of an unnatural enantiomer of merrilactone a: development of an enantioselective desymmetrization strategy. AB - (-)-Merrilactone A [(-)-1], isolated from Illicium merrillianum in 2000, possesses neurite outgrowth activity in cultures of fetal rat cortical neurons, and, therefore, is expected to show therapeutic potential for the treatment of neurodegeneration associated with Alzheimer's and Parkinson's diseases. Apart from its biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. Here, we report the total synthesis of the unnatural enantiomer of merrilactone A [(+)-1], based on a novel desymmetrization strategy. The chiral lithium amide 16g promoted an enantioselective transannular aldol reaction of eight-membered meso-diketone 3d, establishing the absolute stereochemistries of four chiral centers of the cis-bicyclo[3.3.0]octane framework of 1 in a single step. The obtained compound 4d served as a platform for the subsequent functional group manipulations necessary for the construction of (+)-1. Surprisingly, both the natural and unnatural enantiomers of synthetic merrilactone A equally promoted neurite outgrowth in primary neuronal cultures. PMID- 17355152 TI - Site specific N6-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4-diepoxybutane: synthesis and stability at physiological pH. AB - 1,2,3,4-Diepoxybutane (DEB) is an important metabolite of 1,3-butadiene, a high volume industrial chemical classified as a human and animal carcinogen. DEB is a bifunctional alkylating agent that exhibits both mutagenic and cytotoxic activity, presumably a result of its ability to form bifunctional DNA adducts. Initial reactions of DEB with DNA produce 2-hydroxy-3,4-epoxybut-1-yl (HEB) lesions at guanine and adenine nucleobases. The epoxy group of the monoadduct is inherently reactive and can then undergo further reactions, for example, hydrolysis to the corresponding 2,3,4-trihydroxybutyl adducts and/or second alkylation to yield 2,3-butanediol cross-links. In the present work, synthetic DNA 16-mers containing structurally defined racemic N6-(2-hydroxy-3,4-epoxybut-1 yl)-2'-deoxyadenosine (N6-HEB-dA) adducts (5'-AATTATGTXACGGTAG-3', where X = N6 HEB-dA) were prepared by coupling 6-chloropurine-containing oligodeoxynucleotides with 1-amino-2-hydroxy-3,4-epoxybutane. The latter was generated in situ from the corresponding Fmoc-protected amino epoxide. The N6-HEB-dA-containing DNA oligomer was isolated by reverse-phase HPLC, and the presence of N6-HEB-dA in its structure was confirmed by molecular weight determination and by HPLC-UV-ESI+ MS/MS analyses of enzymatic digests. An independently prepared N6-HEB-dA nucleoside served as an authentic standard. The fate of N6-HEB-dA within DNA at physiological conditions in the presence of various nucleophiles (e.g., cysteine, dG, and the complementary DNA strand) was investigated. Under all conditions tested, N6-HEB-dA rapidly cyclized to produce previously unidentified exocyclic dA lesions (t1/2 < 2 h at physiological conditions). Only trace amounts of hydrolyzed and cross-linked products were detected, suggesting that the rate of cyclization was much greater than the rates of other reactions at the epoxide ring. These results indicate that DEB-induced alkylation of N6-adenine in DNA is unlikely to lead to DNA-DNA cross-linking but instead can result in the formation of exocyclic dA adducts. PMID- 17355153 TI - Synthesis and absolute configuration of cis- and trans-opened cyclopenta[cd]pyrene 3,4-oxide N2-deoxyguanosine adducts: conversion to phosphoramidites for oligonucleotide synthesis. AB - Fluorinated alcohols such as trifluoroethanol (TFE) or hexafluoropropan-2-ol (HFP) catalyze addition of the N2-amino group of O6-allyl-3',5'-di-O-(tert butyldimethylsilyl)-2'-deoxyguanosine (3) to cyclopenta[cd]pyrene 3,4-oxide (CPPO). The reaction occurs via a carbocation intermediate at C-3 such that cis- and trans-opened dGuo adducts are formed in a combined yield of approximately 37% together with the 4-ketone and a cis-opened solvent adduct. Fluorinated alcohol mediated regioselective substitution at C-3 of the CPP cis- (11) and trans-3,4 dihydrodiol diacetates (15) with the N2-amino group of 3 proceeded smoothly to give the O6-allyl di-(tert-butyldimethylsilyl) cis- and trans-opened dGuo-adduct acetates (8a,b and 9a,b) in 75-85% yields. The cis-opened adducts predominated (56-70%) from both 11 and 15. Interestingly, trans-3-acetoxy-4-bromo-3,4-dihydro CPP and 3 in TFE or HFP gave a mixture of 8a,b and 9a,b in 75-85% yield with cis:trans adduct ratios similar to those observed for 11 and 15. This observation is consistent with initial formation of a cyclic acetoxonium intermediate followed by formation of the same carbocation as that derived from 11 or 15. Absolute configurations of 8a,b and 9a,b were assigned by using enantiomerically pure (+)-trans-[3S.4S]-dihydrodiol as the starting material, which afforded a single cis-[3R,4S]-dGuo adduct and a single trans-[3S,4S]-dGuo adduct. The optically active trans-3,4-dihydrodiols were obtained by HPLC separation of their bis-(-)-menthoxyacetates. Their absolute configuration was determined by several empirical methods in addition to application of the exciton chirality CD method to their bis-(p-N,N-dimethylamino)benzoates. Removal of all blocking groups from the protected cis- and trans-opened dGuo adducts (8a,b and 9a,b) in three steps (overall yields of >70%) gave the free dGuo adducts, which are useful markers for DNA-binding studies. Adducts 8a,b and 9a,b were also converted to the appropriately protected phosphoramidites in three steps (overall yields of 72 81%). PMID- 17355154 TI - Bacterial plate assays and electrochemical methods: an efficient tandem for evaluating the ability of catechol-thioether metabolites of MDMA ("ecstasy") to induce toxic effects through redox-cycling. AB - Several catechol-thioether metabolites of MDMA (ecstasy), three monoadducts, 5 (glutathion-S-yl)-N-methyl-alpha-methyldopamine (1), 5-(N-acetylcystein-S-yl)-N methyl-alpha-methyldopamine (2), and 5-(cystein-S-yl)-N-methyl-alpha methyldopamine (3), and two bi-adducts, 2,5-bis(glutathion-S-yl)-N-methyl-alpha methyldopamine (4) and 2,5-bis(N-acetylcystein-S-yl)-N-methyl-alpha methyldopamine (5), have been synthesized through an environmentally friendly one pot electrochemical procedure. Their cytotoxicity profiles were further characterized using simple Escherichia coli plate assays and compared with those of N-methyl-alpha-methyldopamine (HHMA), dopamine (DA), and its corresponding catechol-thioether conjugates (monoadducts 6-8 and bi-adducts 9 and 10). Toxicity mediated by reactive oxygen species (ROS-TOX) was detected in the OxyR- assay, using cells sensitive to oxidative stress due to a deficiency in the OxyR protein. Toxicity arising from the high susceptibility of quinone toward endogenous nucleophiles (Q-TOX) was detected using OxyR+ cells, in the presence of tyrosinase, to promote catechol oxidation to the corresponding o-quinone. At the exclusion of 5-(cystein-S-yl) mono-conjugate 3, which was devoid of any toxicity, all compounds produced ROS-TOX, which was enhanced in the presence of tyrosinase, suggesting that the generated o-quinone (or o-quinone-thioether) species can enter redox cycles through its semiquinone radical, leading to the formation of ROS. The sequence order of toxicity was HHMA approximately = 1 approximately = 2 approximately =5 >> 7 > DA approximately = 4 > 10 > 6 > 8. In contrast, no Q-TOX arising from the binding of quinones with cellular nucleophiles was evidenced, even in the presence of tyrosinase. Finally, taking into account that several different pathways could contribute to the overall MDMA toxicity and that HHMA and catechol-thioether conjugates 1-5 have not been undoubtedly established as in vivo toxic metabolites of MDMA, it can be suggested that these compounds could participate in the toxic effects of this drug through the efficiency of redox active quinonoid centers generating ROS. PMID- 17355155 TI - XPS and 1H NMR study of thermally stabilized Rh/CeO2 catalysts submitted to reduction/oxidation treatments. AB - Rh/CeO2 catalysts submitted to different H2 reduction, Ar+ sputtering, and oxidation treatments have been studied by X-ray photoelectron (XPS) and 1H nuclear magnetic resonance (NMR) spectroscopies. Depending on the reduction temperature, two stages have been identified in the reduction of the catalyst: below 473 K, reduction increases the amount of OH and Ce3+ species; above this temperature, reduction produces oxygen vacancies at the surface of the support. Volumetric and microcalorimetric techniques have been used to study hydrogen adsorption on the catalyst, and 1H NMR spectroscopy was used to differentiate hydrogen adsorbed on the metal from that adsorbed on the support. From 1H NMR and TEM results, the main metal particle size (38 A) in the Rh/CeO2 catalyst has been estimated. The influence of the support reduction on the metal adsorption capacity has also been investigated, showing that formation of oxygen vacancies at the metal-support interface enhances the electronic perturbation and decreases the hydrogen adsorption on metal particles. The comparison of data reported on catalysts of high and low surface area supports has shown that both processes are shifted to higher temperatures in the Rh/CeO2 catalyst of lower surface area. PMID- 17355156 TI - Plasma surface modification and characterization of POSS-based nanocomposite polymeric thin films. AB - The effect of a remote oxygen plasma on nanocomposite hybrid polymer thin films of poly[(propylmethacryl-heptaisobutyl-polyhedral oligomeric silsequioxane)-co (methylmethacrylate)] (POSS-MA) has been examined by advancing contact angle, X ray photoelectron spectroscopy (XPS), and variable-angle spectroscopic ellipsometry (VASE). Exposure to a 25 W remote oxygen-containing plasma was found to convert the surface of POSS-MA films from hydrophobic to hydrophilic within 20 s. The exposure time needed for this conversion to occur decreased as the O2/N2 ratio in the plasma environment increased, indicating a positive correlation between the hydrophilicity and the presence of oxygen in the plasma. Local bonding information inferred from high-resolution XPS data showed that the isobutyl bonding to the POSS moiety is replaced with oxygen as a result of plasma exposure. Finally, VASE data demonstrates that increasing the weight percent of POSS in the copolymer significantly impedes the oxygen plasma degradation of POSS MA films. On the basis of these results, a model is presented in which the oxygen plasma removes isobutyl groups from the POSS cages and leaves a SiO2-like surface that is correspondingly more hydrophilic than the surface of the untreated samples and is more resistant to oxidation by the plasma. The ability to modify surfaces in this manner may impact the utility of this material for biomedical applications such as microfluidic devices in which the ability to control surface chemistry is critical. PMID- 17355157 TI - Mechanism of ultraviolet bonding of perfluoropolyethers revisited. AB - The mechanism of ultraviolet (UV) bonding of perfluoropolyether (PFPE) boundary lubricants on magnetic disk surfaces is re-examined experimentally. It is found that UV-emitted photoelectrons may contribute a negligible part, and instead the UV bonding correlates with the direct photodissociation of PFPE molecules. The UV induced photodissociation is demonstrated to occur almost randomly on the PFPE molecular chain. The contribution from photooxidation is eliminated under nitrogen purge. PMID- 17355158 TI - Relaxometric and magnetic characterization of ultrasmall iron oxide nanoparticles with high magnetization. Evaluation as potential T1 magnetic resonance imaging contrast agents for molecular imaging. AB - Here we report on the synthesis of ultrasmall gamma-Fe2O3 nanoparticles (5 nm) presenting a very narrow particle size distribution and an exceptionally high saturation magnetization. The synthesis has been carried out by decomposition of an iron organometallic precursor in an organic medium. The particles were subsequently stabilized in an aqueous solution at physiological pH, and the colloidal dispersions have been thoroughly characterized by complementary techniques. Particular attention has been given to the assessment of the mean particle size by transmission electron microscopy, X-ray diffraction, dynamic light scattering, magnetic, and relaxometric measurements. The good agreement found between the different techniques points to a very narrow particle size distribution. Regarding the magnetic properties, the particles are superparamagnetic at room temperature and present an unusually high saturation magnetization value. In addition, we describe the potential of these particles as specific positive contrast agents for magnetic resonance molecular imaging. PMID- 17355159 TI - Self-assembly and thermal phase transition behavior of unsymmetrical bolaamphiphiles having glucose- and amino-hydrophilic headgroups. AB - The thermal phase transition and self-assembly behaviors in water of the crystalline lamellar films prepared from unsymmetrical bolaamphiphiles, N-(2 aminoethyl)-N'-(beta-d-glucopyranosyl)-alkanediamide [1(n), n = 12, 14, 16, 17, 18, and 20], have been studied using differential scanning calorimetry, polarized light microscopy, variable-temperature (VT) X-ray diffraction (XRD), and VT-IR spectroscopy. The behavior allowed us to classify the bolaamphiphiles into two categories: short chain 1(n) (n = 12, 14, 16, and 17) and long chain 1(n) (n = 18 and 20). On heating, the films of the long chain 1(n) exhibited polymorphism of two crystal phases (Cr1 and Cr2) and one thermotropic mesophase (smectic). These phases proved to consist of unsymmetrical monolayer lipid membranes (MLMs), in which the molecules packed in a parallel fashion. On the other hand, the films of the short chain 1(n) gave a single crystal phase (Cr1) consisting of symmetrical MLMs with antiparallel molecular packing. Scanning transmission electron microscopy and atomic force microscopy revealed that the long chain 1(n) self assembles in alkaline aqueous solutions to form nanotubes with 110-120 nm outer diameters, while the short chain 1(n) produces nanotapes with 80-250 nm widths. XRD and IR measurements revealed that the nanotubes consist of unsymmetrical MLMs, while the nanotapes consist of symmetrical MLMs. The molecular packing of the initial solid phase was essentially maintained even in the self-assemblies in water. The self-assembly process in water allowed the symmetrical MLM films of the short chain 1(n) to convert into the symmetrical MLM nanotapes. Similarly, the unsymmetrical MLM films of the long chain 1(n) were converted into the unsymmetrical MLM nanotubes. PMID- 17355160 TI - Straightforward protein immobilization on Sylgard 184 PDMS microarray surface. AB - In this work, a straightforward technique for protein immobilization on Sylgard 184 is described. The method consists of a direct transfer of dried protein/salt solutions to the PDMS interface during the polymer curing. Such non-conventional treatment of proteins was found to have no major negative consequence on their integrity. The mechanisms of this direct immobilization were investigated using a lysine modified dextran molecule as a model. Clear experimental results suggested that both chemical bounding and molding effect were implicated. As a proof of concept study, three different proteins were immobilized on a single microarray (Arachis hypogaea lectin, rabbit IgG, and human IgG) and used as antigens for capture of chemiluminescent immunoassays. The proteins were shown to be easily recognized by their specific antibodies, giving antibody detection limits in the fmol range. PMID- 17355161 TI - Low-frequency electrophoretic actuation of nanoscale optoentropic transduction mechanisms. AB - Inherent bistabilities within DNA-assembled fluorescent resonant energy transfer systems demonstrated time-varying optical signals in response to an electrophoretic driving force. Frequency responses of electrophoretically driven FRET systems were shown to be sequence specific. Integration of these signals over time gave near single-molecule sensitivity within a high background of autofluorescence. This research suggests that externally driven nanoscale mechanical systems may help improve information flow within morphologically intact specimens. PMID- 17355162 TI - New versus established drugs in venous thromboprophylaxis: efficacy and safety considerations related to timing of administration. AB - European surgeons generally administer thromboprophylaxis with low-molecular weight heparins (LMWHs) at high doses 12 hours preoperatively in response to findings that surgery-related deep-vein thrombosis typically originates at the time of major orthopedic surgery or shortly afterwards. North American surgeons, in contrast, generally administer LMWHs at an almost 50% higher dose than that given in Europe 12-24 hours postoperatively, even though both pre- and postoperative administration are considered suitable in current guidelines. This review therefore examines how close to major orthopedic surgery thromboprophylaxis is administered, and the subsequent effect of timing on clinically relevant efficacy and safety parameters. The trials examined involve fondaparinux sodium (fondaparinux) and (xi)melagatran, in comparison with the established LMWHs enoxaparin sodium (enoxaparin) and dalteparin. In key trials, fondaparinux reduced the risk of asymptomatic and clinical venous thromboembolism (VTE) by 55% compared with enoxaparin, at the expense of a 1.6-fold higher risk of bleeding. While the studies were not designed to compare efficacy endpoints based on clinical outcomes, no significant difference was demonstrated for symptomatic VTE. The fact that the enoxaparin regimen was started at the upper limits of its recommended initiation timeframe may have significantly influenced the results of comparative studies, given that several meta-analyses found that the timing of LMWH initiation significantly influenced its effectiveness on asymptomatic VTE and major bleedings. Compared with once-daily LMWH in European trials, early postoperative doses/regimens of twice-daily (xi)melagatran did not increase severe bleeding and was significantly less effective at preventing asymptomatic total VTE in patients who had undergone total hip-replacement surgery. When used according to the 'knife-to-skin' protocol, the melagatran regimen was superior to enoxaparin in preventing major asymptomatic VTE, but at the cost of a higher rate of major bleeding. In North America, the delayed postoperative administration of (xi)melagatran (oral only) was less effective than the postoperative twice-daily enoxaparin regimen with regard to asymptomatic total and major VTE. Our analysis highlights the fact that differences in efficacy and safety data in clinical trials of thromboprophylaxis might also be linked to differences in the timing of initiation. However, it is not possible to assess the importance of this 'time effect' among other factors considered as drug-specific properties (pharmacokinetics, mode of action, dosage) and evaluate their respective contribution in the observed differences. To avoid unbiased comparison in further studies, the possible effect of timing should be taken into account and, when feasible, both therapies started at the same time. For instance, harmonizing the initiation of thromboprophylaxis 6-8 or 12 hours postoperatively could be two acceptable harmonized options for scheduling in clinical trials. PMID- 17355163 TI - Defining the role of zofenopril in the management of hypertension and ischemic heart disorders. AB - Zofenopril is a specific ACE inhibitor with antihypertensive, remarkable antioxidant, and cardioprotective properties, including the ability to improve endothelial function and protect against ischemia. These beneficial properties of zofenopril are believed to be due primarily to the presence of a sulfhydryl group and the highly lipophilic nature of the agent. As a potent, long-acting ACE inhibitor with tissue selectivity, it is a useful agent for the treatment of a number of cardiovascular diseases. ACE inhibitors block the renin-angiotensin aldosterone system (RAAS) and are recommended in the management of hypertension with associated risk factors because of their renoprotective and cardioprotective effects. There is a robust body of comparative data supporting zofenopril as an effective and well tolerated ACE inhibitor for treating hypertension. Hypertensive patients frequently require combination therapy to adequately control BP. ACE inhibitors combined with a diuretic make a very effective combination, as a result of the synergistic mechanisms of these two drug classes that allow good efficacy and favorable tolerability at low doses. The combination of zofenopril and hydrochlorothiazide is effective and superior to monotherapy with either agent. Clinical studies have demonstrated that early administration of zofenopril in patients with acute myocardial infarction is effective and well tolerated for reducing the incidence of major cardiovascular events in at-risk patients, and it is believed that much of the benefit is a result of the primary cardioprotective effect of zofenopril. PMID- 17355164 TI - Inhibition of the renin-angiotensin system and the prevention of stroke. AB - BP is the most important determinant of the risk of stroke. A small reduction in BP results in a substantial reduction of both ischemic and hemorrhagic stroke. Any of the commonly used antihypertensive drugs lower the incidence of stroke, with larger reductions in BP resulting in larger reductions in risk. Experimental evidence has linked the renin-angiotensin system (RAS) to the development and progression of cerebrovascular disease. Inhibition of the RAS has beneficial cerebrovascular effects and may reduce the risk of stroke in a manner possibly independent from the alterations of BP. Some clinical trials even suggest that ACE inhibitors and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) exert cerebroprotective effects beyond BP lowering, but the evidence is controversial. Studies on specific protective actions of antihypertensive drugs are generally hampered by the fact that any treatment related difference in BP may play a dominant role in the prevention of stroke. There are also indications that the protective potency of ARBs might be superior to that of ACE inhibitors, due to their differential activation of angiotensin II type 2 receptors, but the clinical relevance of this mechanism is unclear. Some studies in primary prevention of stroke, acute stroke, and secondary prevention show advantages for ARBs beyond controlling BP alone. In primary prevention, the LIFE randomized trial showed a significant difference in stroke rate in favor of losartan compared with atenolol despite similar reductions in BP. In acute stroke, the role of hypertension and its treatment remains controversial. ACCESS, however, suggested that an ARB is safe in hypertensive acute stroke patients and may offer advantages independent from BP control. In secondary stroke prevention, there are very few antihypertensive trials. These trials show that BP lowering is at least as successful as in primary prevention, but the absolute stroke risk is much higher. An ACE inhibitor was effective compared with placebo in the PROGRESS trial. The MOSES study showed that eprosartan prevented vascular events more effectively than nitrendipine, despite similar BP-lowering effects. Hypertension is not only the most important risk factor for stroke, but is also closely correlated with cognitive decline and dementia. Therefore, prevention of cognitive decline or even improvement of slightly diminished brain function should be an important goal for antihypertensive treatment in the future. Some clinical data suggest advantages for ACE inhibitors, ARBs, and calcium channel antagonists. Currently, however, the existing data are not sufficient for clinical recommendations. Therefore, ongoing trials will further define the exact role of inhibitors of the RAS and are urgently needed in secondary prevention, in acute stroke, and in the prevention of cognitive decline. PMID- 17355165 TI - Management of dyslipidemia in the metabolic syndrome: recommendations of the Spanish HDL-Forum. AB - In order to characterize the metabolic syndrome it becomes necessary to establish a number of diagnostic criteria. Because of its impact on cardiovascular morbidity/mortality, considerable attention has been focussed on the dyslipidemia accompanying the metabolic syndrome. The aim of this review is to highlight the fundamental aspects of the pathophysiology, diagnosis, and the treatment of the metabolic syndrome dyslipidemia with recommendations to clinicians. The clinical expression of the metabolic syndrome dyslipidemia is characterized by hypertriglyceridemia and low levels of high-density lipoprotein-cholesterol (HDL C). In addition, metabolic syndrome dyslipidemia is associated with high levels of apolipoprotein (apo) B-100-rich particles of a particularly atherogenic phenotype (small dense low-density lipoprotein-cholesterol [LDL-C]. High levels of triglyceride-rich particles (very low-density lipoprotein) are also evident both at baseline and in overload situations (postprandial hyperlipidemia). Overall, the 'quantitative' dyslipidemia characterized by hypertriglyceridemia and low levels of HDL-C and the 'qualitative' dyslipidemia characterized by high levels of apo B-100- and triglyceride-rich particles, together with insulin resistance, constitute an atherogenic triad in patients with the metabolic syndrome. The therapeutic management of the metabolic syndrome, regardless of the control of the bodyweight, BP, hyperglycemia or overt diabetes mellitus, aims at maintaining optimum plasma lipid levels. Therapeutic goals are similar to those for high-risk situations because of the coexistence of multiple risk factors. The primary goal in treatment should be achieving an LDL-C level of <100 mg/dL (or <70 mg/dL in cases with established ischemic heart disease or risk equivalents). A further goal is increasing the HDL-C level to >or=40 mg/dL in men or 50 mg/dL in women. A non-HDL-C goal of 130 mg/dL should also be aimed at in cases of hypertriglyceridemia. Lifestyle interventions, such as maintaining an adequate diet, and a physical activity program, constitute an essential part of management. Nevertheless, when pharmacologic therapy becomes necessary, fibrates and HMG-CoA reductase inhibitors (statins) are the most effective drugs in controlling the metabolic syndrome hyperlipidemia, and are thus the drugs of first choice. Fibrates are effective in lowering triglycerides and increasing HDL C levels, the two most frequent abnormalities associated with the metabolic syndrome, and statins are effective in lowering LDL-C levels, even though hypercholesterolemia occurs less frequently. In addition, the combination of fibrates and statins is highly effective in controlling abnormalities of the lipid profile in patients with the metabolic syndrome. PMID- 17355166 TI - Current management of peripheral arterial occlusive disease: a review of pharmacologic agents and other interventions. AB - Peripheral arterial occlusive disease (PAOD) of the lower extremities is becoming more prevalent worldwide. Nonsurgical treatment options provide the foundation for management. Lifestyle and risk factor modification should be emphasized in this patient population because of the associated adverse cardiovascular events. This includes implementation of a regular walking and smoking-cessation programs, aggressive control of hyperlipidemia, hypertension and diabetes mellitus, and treatment of hyperhomocysteinemia. Antiplatelet agents such as aspirin (acetylsalicylic acid) or clopidogrel are not specifically indicated for claudication but these drugs should be used in all patients with PAOD to prevent secondary ischemic events. Currently, cilostazol is the only US FDA approved agent that appears effective for the treatment of claudication symptoms. Several agents have been used with success outside of the US and others are still undergoing testing. Definitive recommendations cannot be made on the use of these drugs until further evaluation is completed. Ongoing research with new strategies for angiogenesis and the use of progenitor cells has yielded encouraging results, particularly for patients with critical limb ischemia and limited options. Advances in endovascular technology over the last several years have greatly enhanced the ability to diagnose and treat specific anatomic lesions that previously would have required open surgical correction. The use of percutaneous transluminal angioplasty and stents in the lower extremities has had considerable success when following specific guidelines such as those set forth by the TransAtlantic Inter-Society Consensus Working Group. PMID- 17355167 TI - Current management of transient ischemic attack. AB - Transient ischemic attack (TIA) is a precursor to ischemic stroke. At least half of patients with TIA have a new, small ischemic lesion demonstrable on magnetic resonance imaging using a diffusion weighted sequence. The risk of subsequent major stroke is 10-20% in the next 3 months with much of that risk front-loaded in the first week. Strategies to identify and treat high-risk patients need to be defined. The optimal treatment approach and the timing of interventions, both medical and surgical, remains unknown. In general, aspirin is the first line of treatment to prevent further stroke. Other antiplatelet agents such as clopidogrel alone or in combination with aspirin and the combination aspirin/extended-release dipyridamole may be administered. Endarterectomy or carotid stenting is of great benefit to patients with TIA secondary to stenosis in the extracranial carotid artery. PMID- 17355168 TI - Aldosterone antagonists: the most underutilized class of heart failure medications. AB - BACKGROUND: Aldosterone antagonists have been proven to be beneficial in severe heart failure (HF) as a result of systolic dysfunction. We sought to determine if there is a disparity in their utilization compared with ACE inhibitors and beta adrenoceptor antagonists (beta-blockers). METHODS: In the first part of the study, we asked physicians to answer a questionnaire presenting a hypothetical HF patient. In the second part, we reviewed hospital charts of patients with HF exacerbation. RESULTS: Spironolactone was used less frequently than other drugs. At home, 75.0% of patients were receiving ACE inhibitors, 66.7% received beta blockers, and 38.2% received spironolactone (p < 0.001). During the admission, 93.1% of patients received ACE inhibitors and 58.3% received spironolactone (p < 0.001). CONCLUSIONS: Despite good evidence, underutilization of aldosterone antagonists in patients matching the population of the RALES (Randomized Aldactone Evaluation Study) trial persists in both outpatient and inpatient settings. The difference between the usage of ACE inhibitors and spironolactone is significant in patients with systolic dysfunction equally qualifying for both medications. PMID- 17355169 TI - X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. AB - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X-linked deficiency states associated with protection against malaria, notably in Africa where the A- form of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation) have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection. METHODS AND FINDINGS: We conducted large case-control studies of the A- form of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies. CONCLUSIONS: The A- form of G6PD deficiency in Africa is under strong natural selection from the preferential protection it provides to hemizygous males against life-threatening malaria. Little or no such protection is present among heterozygous females. Although these conclusions are consistent with data from at least one previous study, they have not heretofore been realized to our knowledge, and they therefore give fresh perspectives on malaria protection by G6PD deficiency as an X-linked trait. PMID- 17355170 TI - Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. AB - BACKGROUND: Malaria vaccines based on the 19-kDa region of merozoite surface protein 1 (MSP-1(19)) derived from the 3D7 strain of Plasmodium falciparum are being tested in clinical trials in Africa. Knowledge of the distribution and natural dynamics of vaccine antigen polymorphisms in populations in which malaria vaccines will be tested will guide vaccine design and permit distinction between natural fluctuations in genetic diversity and vaccine-induced selection. METHODS AND FINDINGS: Using pyrosequencing, six single-nucleotide polymorphisms in the nucleotide sequence encoding MSP-1(19) were genotyped from 1,363 malaria infections experienced by 100 children who participated in a prospective cohort study in Mali from 1999 to 2001. The frequencies of 14 MSP-1(19) haplotypes were compared over the course of the malaria transmission season for all three years, in three age groups, and in consecutive infections within individuals. While the frequency of individual MSP-1(19) haplotypes fluctuated, haplotypes corresponding to FVO and FUP strains of P. falciparum (MSP-1(19) haplotypes QKSNGL and EKSNGL, respectively) were most prevalent during three consecutive years and in all age groups with overall prevalences of 46% (95% confidence interval [CI] 44%-49%) and 36% (95% CI 34%-39%), respectively. The 3D7 haplotype had a lower overall prevalence of 16% (95% CI 14%-18%). Multiplicity of infection based on MSP-1(19) was higher at the beginning of the transmission season and in the oldest individuals (aged > or =11 y). Three MSP-1(19) haplotypes had a reduced frequency in symptomatic infections compared to asymptomatic infections. Analyses of the dynamics of MSP-1(19) polymorphisms in consecutive infections implicate three polymorphisms (at positions 1691, 1700, and 1701) as being particularly important in determining allele specificity of anti-MSP-1(19) immunity. CONCLUSIONS: Parasites with MSP-1(19) haplotypes different from that of the leading vaccine strain were consistently the most prevalent at a vaccine trial site. If immunity elicited by an MSP-1-based vaccine is allele-specific, a vaccine based on either the FVO or FUP strain might have better initial efficacy at this site. This study, to our knowledge the largest of its kind to date, provides molecular information needed to interpret population responses to MSP-1-based vaccines and suggests that certain MSP-1(19) polymorphisms may be relevant to cross-protective immunity. PMID- 17355172 TI - Structural and functional diversity of the microbial kinome. AB - The eukaryotic protein kinase (ePK) domain mediates the majority of signaling and coordination of complex events in eukaryotes. By contrast, most bacterial signaling is thought to occur through structurally unrelated histidine kinases, though some ePK-like kinases (ELKs) and small molecule kinases are known in bacteria. Our analysis of the Global Ocean Sampling (GOS) dataset reveals that ELKs are as prevalent as histidine kinases and may play an equally important role in prokaryotic behavior. By combining GOS and public databases, we show that the ePK is just one subset of a diverse superfamily of enzymes built on a common protein kinase-like (PKL) fold. We explored this huge phylogenetic and functional space to cast light on the ancient evolution of this superfamily, its mechanistic core, and the structural basis for its observed diversity. We cataloged 27,677 ePKs and 18,699 ELKs, and classified them into 20 highly distinct families whose known members suggest regulatory functions. GOS data more than tripled the count of ELK sequences and enabled the discovery of novel families and classification and analysis of all ELKs. Comparison between and within families revealed ten key residues that are highly conserved across families. However, all but one of the ten residues has been eliminated in one family or another, indicating great functional plasticity. We show that loss of a catalytic lysine in two families is compensated by distinct mechanisms both involving other key motifs. This diverse superfamily serves as a model for further structural and functional analysis of enzyme evolution. PMID- 17355173 TI - Synthetic biology: caught between property rights, the public domain, and the commons. PMID- 17355171 TI - The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families. AB - Metagenomics projects based on shotgun sequencing of populations of micro organisms yield insight into protein families. We used sequence similarity clustering to explore proteins with a comprehensive dataset consisting of sequences from available databases together with 6.12 million proteins predicted from an assembly of 7.7 million Global Ocean Sampling (GOS) sequences. The GOS dataset covers nearly all known prokaryotic protein families. A total of 3,995 medium- and large-sized clusters consisting of only GOS sequences are identified, out of which 1,700 have no detectable homology to known families. The GOS-only clusters contain a higher than expected proportion of sequences of viral origin, thus reflecting a poor sampling of viral diversity until now. Protein domain distributions in the GOS dataset and current protein databases show distinct biases. Several protein domains that were previously categorized as kingdom specific are shown to have GOS examples in other kingdoms. About 6,000 sequences (ORFans) from the literature that heretofore lacked similarity to known proteins have matches in the GOS data. The GOS dataset is also used to improve remote homology detection. Overall, besides nearly doubling the number of current proteins, the predicted GOS proteins also add a great deal of diversity to known protein families and shed light on their evolution. These observations are illustrated using several protein families, including phosphatases, proteases, ultraviolet-irradiation DNA damage repair enzymes, glutamine synthetase, and RuBisCO. The diversity added by GOS data has implications for choosing targets for experimental structure characterization as part of structural genomics efforts. Our analysis indicates that new families are being discovered at a rate that is linear or almost linear with the addition of new sequences, implying that we are still far from discovering all protein families in nature. PMID- 17355174 TI - Sorcerer II: the search for microbial diversity roils the waters. PMID- 17355175 TI - CAMERA: a community resource for metagenomics. PMID- 17355176 TI - The Sorcerer II Global Ocean Sampling expedition: northwest Atlantic through eastern tropical Pacific. AB - The world's oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition. These samples, collected across a several-thousand km transect from the North Atlantic through the Panama Canal and ending in the South Pacific yielded an extensive dataset consisting of 7.7 million sequencing reads (6.3 billion bp). Though a few major microbial clades dominate the planktonic marine niche, the dataset contains great diversity with 85% of the assembled sequence and 57% of the unassembled data being unique at a 98% sequence identity cutoff. Using the metadata associated with each sample and sequencing library, we developed new comparative genomic and assembly methods. One comparative genomic method, termed "fragment recruitment," addressed questions of genome structure, evolution, and taxonomic or phylogenetic diversity, as well as the biochemical diversity of genes and gene families. A second method, termed "extreme assembly," made possible the assembly and reconstruction of large segments of abundant but clearly nonclonal organisms. Within all abundant populations analyzed, we found extensive intra-ribotype diversity in several forms: (1) extensive sequence variation within orthologous regions throughout a given genome; despite coverage of individual ribotypes approaching 500-fold, most individual sequencing reads are unique; (2) numerous changes in gene content some with direct adaptive implications; and (3) hypervariable genomic islands that are too variable to assemble. The intra-ribotype diversity is organized into genetically isolated populations that have overlapping but independent distributions, implying distinct environmental preference. We present novel methods for measuring the genomic similarity between metagenomic samples and show how they may be grouped into several community types. Specific functional adaptations can be identified both within individual ribotypes and across the entire community, including proteorhodopsin spectral tuning and the presence or absence of the phosphate binding gene PstS. PMID- 17355177 TI - Environmental shotgun sequencing: its potential and challenges for studying the hidden world of microbes. PMID- 17355178 TI - Global ocean sampling collection. PMID- 17355179 TI - Two oppositely localised frizzled RNAs as axis determinants in a cnidarian embryo. AB - In phylogenetically diverse animals, including the basally diverging cnidarians, "determinants" localised within the egg are responsible for directing development of the embryonic body plan. Many such determinants are known to regulate the Wnt signalling pathway, leading to regionalised stabilisation of the transcriptional coregulator beta-catenin; however, the only strong molecular candidate for a Wnt activating determinant identified to date is the ligand Wnt11 in Xenopus. We have identified embryonic "oral-aboral" axis determinants in the cnidarian Clytia hemisphaerica in the form of RNAs encoding two Frizzled family Wnt receptors, localised at opposite poles of the egg. Morpholino-mediated inhibition of translation showed that CheFz1, localised at the animal pole, activates the canonical Wnt pathway, promotes oral fates including gastrulation, and may also mediate global polarity in the ectoderm. CheFz3, whose RNA is localised at the egg vegetal cortex, was found to oppose CheFz1 function and to define an aboral territory. Active downregulation mechanisms maintained the reciprocal localisation domains of the two RNAs during early development. Importantly, ectopic expression of either CheFz1 or CheFz3 was able to redirect axis development. These findings identify Frizzled RNAs as axis determinants in Clytia, and have implications for the evolution of embryonic patterning mechanisms, notably that diverse Wnt pathway regulators have been adopted to initiate asymmetric Wnt pathway activation. PMID- 17355180 TI - Enhancement of SMN2 exon 7 inclusion by antisense oligonucleotides targeting the exon. AB - Several strategies have been pursued to increase the extent of exon 7 inclusion during splicing of SMN2 (survival of motor neuron 2) transcripts, for eventual therapeutic use in spinal muscular atrophy (SMA), a genetic neuromuscular disease. Antisense oligonucleotides (ASOs) that target an exon or its flanking splice sites usually promote exon skipping. Here we systematically tested a large number of ASOs with a 2'-O-methoxy-ethyl ribose (MOE) backbone that hybridize to different positions of SMN2 exon 7, and identified several that promote greater exon inclusion, others that promote exon skipping, and still others with complex effects on the accumulation of the two alternatively spliced products. This approach provides positional information about presumptive exonic elements or secondary structures with positive or negative effects on exon inclusion. The ASOs are effective not only in cell-free splicing assays, but also when transfected into cultured cells, where they affect splicing of endogenous SMN transcripts. The ASOs that promote exon 7 inclusion increase full-length SMN protein levels, demonstrating that they do not interfere with mRNA export or translation, despite hybridizing to an exon. Some of the ASOs we identified are sufficiently active to proceed with experiments in SMA mouse models. PMID- 17355181 TI - An aromatic sensor with aversion to damaged strands confers versatility to DNA repair. AB - It was not known how xeroderma pigmentosum group C (XPC) protein, the primary initiator of global nucleotide excision repair, achieves its outstanding substrate versatility. Here, we analyzed the molecular pathology of a unique Trp690Ser substitution, which is the only reported missense mutation in xeroderma patients mapping to the evolutionary conserved region of XPC protein. The function of this critical residue and neighboring conserved aromatics was tested by site-directed mutagenesis followed by screening for excision activity and DNA binding. This comparison demonstrated that Trp690 and Phe733 drive the preferential recruitment of XPC protein to repair substrates by mediating an exquisite affinity for single-stranded sites. Such a dual deployment of aromatic side chains is the distinctive feature of functional oligonucleotide/oligosaccharide-binding folds and, indeed, sequence homologies with replication protein A and breast cancer susceptibility 2 protein indicate that XPC displays a monomeric variant of this recurrent interaction motif. An aversion to associate with damaged oligonucleotides implies that XPC protein avoids direct contacts with base adducts. These results reveal for the first time, to our knowledge, an entirely inverted mechanism of substrate recognition that relies on the detection of single-stranded configurations in the undamaged complementary sequence of the double helix. PMID- 17355183 TI - Re: Relationship between vaccine vial monitors and cold chain infrastructure in a rural district of India. PMID- 17355182 TI - DNA-dependent protein kinase inhibits AID-induced antibody gene conversion. AB - Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID)-dependent hypermutation of Ig V(D)J rearrangements and Ig S regions, respectively, in activated B cells. AID deaminates deoxycytidine bases in Ig genes, converting them into deoxyuridines. In V(D)J regions, subsequent excision of the deaminated bases by uracil-DNA glycosylase, or by mismatch repair, leads to further point mutation or gene conversion, depending on the species. In Ig S regions, nicking at the abasic sites produced by AID and uracil-DNA glycosylases results in staggered double-strand breaks, whose repair by nonhomologous end joining mediates Ig class switching. We have tested whether nonhomologous end joining also plays a role in V(D)J hypermutation using chicken DT40 cells deficient for Ku70 or the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Inactivation of the Ku70 or DNA-PKcs genes in DT40 cells elevated the rate of AID-induced gene conversion as much as 5-fold. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion. PMID- 17355184 TI - Studying nursing in a rural setting: are students adequately supported and prepared for rural practice? A pilot study. AB - INTRODUCTION: A rural nursing program has a vital role in improving the recruitment and retention of nurses in rural and remote settings. A small pilot study was conducted to explore the views and experiences of the first cohort of undergraduate nursing students who completed a rurally based bachelor of nursing program which commenced in 2002 in Renmark, South Australia. The participants were eight current undergraduate nursing students who were part of the first cohort of nursing students nearing completion of the program. The pilot study set out to explore support provided to rural nursing students studying in a rural setting; to investigate whether rural nursing students feel adequately prepared for rural clinical practice near completion of the nursing program; to identify the challenges and highlights of studying rurally; and to explore the probability of retention and recruitment of future nursing graduates in a rural setting. METHODS: The method used was a descriptive, exploratory, web-based survey. Quantitative data were limited to descriptive statistics of demographic characteristics, career goals, graduate nurse program and future employment intentions, level of support, preparation for practice, challenges and highlights of rural study and clinical placements. Qualitative responses to open-ended questions were content analysed to identify common themes. FINDINGS: This study found between two and four participants indicated they received no support from academic, administrative staff and clinical facilitators from the city campus. Five participants (63%) indicated they received no financial support during their studies. Seven of the participants (88%) surveyed, indicated an intention to undertake a graduate nurse program and the same number indicated they would be living in a rural or remote area in 5 years time. Six participants (75%) indicated they were prepared with regard to their 'attitude' towards their future practice as a registered nurse. The study identified some of the challenging issues of a rurally based program, such as 'realising that if you miss a day you are actually missing a whole week's worth of lectures', as well as the positive and unique aspects of rural study, 'not having to leave the family to travel to the city'. CONCLUSION: This study indicates the rural placement of the bachelor of nursing program has been of benefit to this particular community and is a positive outcome for the South Australian rural nursing workforce. The study shows that students actively sought nursing employment in a rural setting, and identifies highlights experienced by students and the advantages associated with remaining at home (as opposed to relocating) while enjoying the benefits of smaller class sizes. The challenges of rural study were issues such as limited lecture times, compared with the city campus, which often caused a disproportionate workload for rural students on alternate weeks during the study term. The quality of the delivery of some lectures was also an issue for some students. This study determined that a lack of support was encountered by students, and that further investigation is warranted. Greater consideration will be required to address the delivery of the program together with the future availability and accessibility of further university rurally based nursing programs. PMID- 17355186 TI - Engineering an improved cell cycle-regulatable herpes simplex virus type 1 amplicon vector with enhanced transgene expression in proliferating cells yet attenuated activities in resting cells. AB - We previously generated a herpes simplex virus type 1 (HSV-1)-based amplicon vector (denoted pC8-36) in which gene expression from the minimal cyclin A promoter is repressed by preventing the binding of a trans-activating protein, Gal4-NF-YA, to it through selective interaction with the transcriptional repressor protein CDF-1. Because CDF-1 is absent in actively dividing cells, transgene expression conferred by the pC8-36 vector is therefore cell cycle dependent. As gene therapy evolves to become a promising therapeutic modality for many human diseases, there is an increasing need to further improve the kinetics of gene regulation. In the present study, we examined whether the availability of more binding sites for CDF-1 repressor proteins could enhance transgene expression. Using an overlap extension polymerase chain reaction (PCR) method, the CDE and CHR elements within the minimum cyclin A promoter were multimerized to contain two, three, and six copies of the designated CDE/CHR sequence. Interestingly, our results demonstrated that six-copy CDE/CHR sequence motifs (pC8-6CC-Luc) conferred an approximately 20-fold increase in the ratio of cell cycle regulation compared with the previous reported construct. Further, the overall transcriptional activities mediated by pC8-6CC-Luc were stronger compared with the native human survivin promoter, which consists of three copies of the CDE element and one copy of the CHR element. pC8-6CC-Luc contained, in essence, only the synthetic six-copy CDE/CHR sequence motif (about 262 bp). In comparison with other native endogenous promoters, which usually contain many other transcription binding sites, pC8-6CC-Luc amplicon vectors should confer better regulated and consistent transgene expression and may be considered a gene delivery vector of choice to target actively proliferating tumor cells. PMID- 17355187 TI - A synthetic vision system using directionally selective motion detectors to recognize collision. AB - Reliably recognizing objects approaching on a collision course is extremely important. A synthetic vision system is proposed to tackle the problem of collision recognition in dynamic environments. The system combines the outputs of four whole-field motion-detecting neurons, each receiving inputs from a network of neurons employing asymmetric lateral inhibition to suppress their responses to one direction of motion. An evolutionary algorithm is then used to adjust the weights between the four motion-detecting neurons to tune the system to detect collisions in two test environments. To do this, a population of agents, each representing a proposed synthetic visual system, either were shown images generated by a mobile Khepera robot navigating in a simplified laboratory environment or were shown images videoed outdoors from a moving vehicle. The agents had to cope with the local environment correctly in order to survive. After 400 generations, the best agent recognized imminent collisions reliably in the familiar environment where it had evolved. However, when the environment was swapped, only the agent evolved to cope in the robotic environment still signaled collision reliably. This study suggests that whole-field direction-selective neurons, with selectivity based on asymmetric lateral inhibition, can be organized into a synthetic vision system, which can then be adapted to play an important role in collision detection in complex dynamic scenes. PMID- 17355188 TI - Synchronization phenomena in surface-reaction models of protocells. AB - A class of generic models of protocells is introduced, which are inspired by the Los Alamos bug hypothesis but which, due to their abstraction level, can be applied to a wider set of detailed protocell hypotheses. These models describe the coupled growth of the lipid container and of the self-replicating molecules. A technique to analyze the dynamics of populations of such protocells is described, which couples a continuous-time formalism for the growth between two successive cell divisions, and a discrete map that relates the quantity of self replicating molecules in successive generations. This technique allows one to derive several properties in an analytical way. It is shown that, under fairly general assumptions, the two growth rates synchronize, so that the lipid container doubles its size when the number of self-replicating molecules has also doubled--thus giving rise to exponential growth of the population of protocells. Such synchronization had been postulated a priori in previous models of protocells; here it is an emergent property. We also compare the rate of duplication of two populations generated by two different protocells with different kinds of self-replicating molecules, considering the interesting case where the rate of self-replication of one kind is higher than that of the other, but its contribution to the container growth rate is smaller. It is shown that in this case the population of offspring of the protocell with the faster replicating molecule will eventually grow faster than the other. The case where two different types of self-replicating monomers are present in the same protocell is also analyzed, and it is shown that, if the replication follows a first-order kinetic equation, then the faster replicator eventually displaces the slower one, whereas if the growth is sublinear the two coexist. It is also proven by an appropriate rescaling of time that the results that concern the system asymptotic dynamics hold both for micelles and vesicles. PMID- 17355189 TI - Evolving virtual creatures and catapults. AB - We present a system that can evolve the morphology and the controller of virtual walking and block-throwing creatures (catapults) using a genetic algorithm. The system is based on Sims' work, implemented as a flexible platform with an off-the shelf dynamics engine. Experiments aimed at evolving Sims-type walkers resulted in the emergence of various realistic gaits while using fairly simple objective functions. Due to the flexibility of the system, drastically different morphologies and functions evolved with only minor modifications to the system and objective function. For example, various throwing techniques evolved when selecting for catapults that propel a block as far as possible. Among the strategies and morphologies evolved, we find the drop-kick strategy, as well as the systematic invention of the principle behind the wheel, when allowing mutations to the projectile. PMID- 17355190 TI - An artificial ecosystem: emergent dynamics and lifelike properties. AB - We discuss modeling and analysis of an artificial ecosystem. The ecosystem consists of basic elements, scents, plants, and animals. There are two species of animals: worms and beetles. As beetles absorb energy from worms, which absorb energy from blades of grass, which absorb energy from water, there is a food chain connecting animals to basic elements. The novelty of our approach lies in the modeling technique: we model the entire ecosystem using a single particle system. Consequently, the physical interaction dynamics not only shows emergent dynamics, but also some interesting lifelike properties. As the main contribution, we formalize the particle system and use it to model and analyze the ecosystem. We consider here several scenarios with nontrivial interaction dynamics. PMID- 17355191 TI - "Life is a verb": inflections of artificial life in cultural context. AB - This review essay surveys recent literature in the history of science, literary theory, anthropology, and art criticism dedicated to exploring how the artificial life enterprise has been inflected by--and might also reshape--existing social, historical, cognitive, and cultural frames of thought and action. The piece works through various possible interpretations of Kevin Kelly's phrase "life is a verb," in order to track recent shifts in cultural studies of artificial life from an aesthetic of critique to an aesthetic of conversation, discerning in the process different styles of translating between the concerns of the humanities, social sciences, natural sciences, and sciences of the artificial. PMID- 17355195 TI - Tell me again what it is that you do. AB - My job at Pullman, Washington, starting in 1965, was to control the root diseases of wheat and barley, focusing first on fusarium root and crown rot, then including take-all and pythium and rhizoctonia root rots. In the absence of viable alternatives, the agronomic approaches used were implemented through design of cereal-based cropping systems. Starting in the late 1970s, the mission focused further on cereal-intensive direct-seed (no-till) cropping systems. A team effort demonstrated the role of indigenous antibiotic-producing fluorescent pseudomonads in the widespread decline of take-all in response to monoculture wheat (or barley-wheat sequences). Today, the suppression of take-all by these beneficial rhizobacteria is the centerpiece of an integrated system that augments take-all decline while limiting pythium and rhizoctonia root rots and fusarium root and crown rot in direct-seed systems. In such systems, "crop rotation" takes the form of different sequences of winter and spring wheat, barley and triticale varieties, and market classes, all susceptible to all four root diseases. PMID- 17355196 TI - An interview with Keith V. Wood. PMID- 17355198 TI - Plasma membrane assays and three-compartment image cytometry for high content screening. AB - High throughput image cytometers analyze individual cells in digital photomicrographs by first assigning pixels within each image to plasma membrane, cytoplasm, nucleus, or other regions. In this study, we report on a novel algorithm that: 1) identifies plasma membrane regions to measure changes in plasma membrane-associated proteins (protein kinase C [PKC] alpha, N-cadherin, E cadherin, vascular endothelium [VE]-cadherin, and pan-cadherin) that regulate cell division, migration, and adhesion and 2) delineates the cell for generalized three-compartment image cytometry. Validation assays were performed for these proteins on cells cultured in 96-well plates and also for tissue sections obtained from transgenic and chemical carcinogenic models of skin cancer. The algorithm successfully quantified phorbol 12-myristate 13-acetate (PMA)-induced plasma membrane localization of PKCalpha in HeLa cells (Z' of 0.88). Additionally, PMA activated translocation to the plasma membrane at P < .01 of N cadherin (in HeLa cells), E-cadherin (in A431 cells), and VE-cadherin (in human dermal microvascular endothelial cells), suggesting a relationship between PKCalpha activity and cadherin localization. For VE-cadherin, a Z' of 0.52 was obtained between serum-free medium, which increased VE-cadherin, and EGTA, which diminished VE-cadherin at the plasma membrane. For sections obtained from the transgenic skin cancer model, analysis of images with the plasma membrane algorithm revealed that tumor cells exhibited cadherin expression that was just 34% of that expressed by surrounding normal tissue; furthermore, tumor cells expressed elevated DNA content, consistent with development of aneuploidy. In contrast, increased DNA content did not occur for tumor cells produced by chemical carcinogenesis. The results demonstrate that this new algorithm for plasma membrane image cytometry enables statistically significant analyses in a variety of applications in both cultured cells and tissue sections. PMID- 17355199 TI - Chemical genetic transcriptional fingerprinting for selectivity profiling of kinase inhibitors. AB - The importance of protein kinases as a major class of drug targets across multiple diseases has generated a critical need for technologies that enable the identification of potent and selective kinase inhibitors. Bruton's tyrosine kinase (Btk) is a compelling drug target in multiple therapeutic areas, including systemic lupus erythematosus, asthma, rheumatoid arthritis, and B cell malignancies. We have combined potent, selective kinase inhibition through chemical genetics with gene expression profiling to identify a "fingerprint" of transcriptional changes associated with selective Btk kinase inhibition. The Btk transcriptional fingerprint shows remarkable relevance for Btk's biological roles and was used for functional selectivity profiling of two kinase inhibitor compounds. The fingerprint was able to rank the compounds by relative selectivity for Btk, and revealed broader off-target effects than observed in a broad panel of biochemical kinase cross screens. In addition to being useful for functional selectivity profiling, the fingerprint genes are themselves potential preclinical and clinical biomarkers for developing Btk-directed therapies. PMID- 17355200 TI - Identification of small molecule ceramide kinase inhibitors using a homogeneous chemiluminescence high throughput assay. AB - Lipid kinases have emerged as potentially important therapeutic targets in oncology and inflammation. Ceramide kinase (CERK) is a lipid kinase that catalyzes the formation of ceramide-1-phosphate from ceramide, a sphingolipid that is a key mediator of cellular apoptosis. Ceramide-1-phosphate has been shown to enhance the production of pro-inflammatory eicosonoids, to promote cell proliferation, and potentially to reduce intracellular ceramide levels by inhibition of acidic sphingomyelinases. Here we describe a homogeneous chemiluminescence assay that directly measures the ceramide-dependent ATP depletion by recombinant full-length human CERK. As compared to reported CERK assays that have limitations on compound throughput, the chemiluminescence assay has been miniaturized to a 1,536-well microtiter plate format and utilized to screen an ultra-large compound library (>4 million compounds). Multiple chemical scaffolds have been identified as CERK kinase inhibitors and characterized mechanistically, which to our knowledge represent the first known small molecule CERK inhibitors with nanomolar activities. These compounds can serve as tools to further elucidate the CERK pathway and its role in ceramide metabolism and human diseases. PMID- 17355201 TI - A high throughput luminescent assay for glycogen synthase kinase-3beta inhibitors. AB - A high throughput luminescent assay based on the Kinase-Glo() system (Promega, Madison, WI) has been developed for screening against glycogen synthase kinase 3beta (GSK-3beta). Careful optimization of assay parameters allowed us to develop a robust, reproducible, and sensitive assay. Its usefulness has been demonstrated in a high throughput screening run when screening 55,000 compounds. This campaign yielded five chemical classes of hits, including several highly potent GSK-3beta inhibitors. PMID- 17355202 TI - A cell-based assay for IkappaBalpha stabilization using a two-color dual luciferase-based sensor. AB - A cell-sensor assay for stabilization of IkappaBalpha was developed in the activated B cell-like diffuse large B-cell lymphoma cell line OCI-Ly3. This cell line expresses known nuclear factor kappaB (NFkappaB) target genes due to high constitutive activity of IkappaB kinase (IKK), which phosphorylates the protein IkappaBalpha leading to proteasomal degradation of IkappaBalpha and activation of NFkappaB. The cell-sensor assay uses green and red light-emitting beetle luciferases, with the green luciferase fused to IkappaBalpha (IkappaBalpha-CBG68) and the red luciferase (CBR) present in its native state. The IkappaBalpha-CBG68 reporter functions as a sensor of IKK and proteasome activity, while CBR serves to normalize for cell number and nonspecific effects. Both reporter constructs were stably integrated and placed under the control of an inducible promoter system, which increased fold responsiveness to inhibitors when assay incubations were performed simultaneous to reporter induction by doxycycline. The assay was miniaturized to a 1,536-well plate format and showed a Z' of 0.6; it was then used to panel 2,677 bioactive compounds by a concentration-response-based screening strategy. The concentration-effect curves for the IkappaBalpha-CBG68 and CBR signals were then used to identify specific stabilizers of IkappaBalpha, such as IKK inhibitors or proteasome inhibitors, which increased the doxycycline induced rise in IkappaBalpha-CBG68 without affecting the rise in CBR. Known and unexpected inhibitors of NFkappaB signaling were identified from the bioactive collection. We describe here the development and performance of this assay, and discuss the merits of its specific features. PMID- 17355203 TI - High capacity homogeneous non-radioactive cortisol detection assays for human 11beta-hydroxysteroid dehydrogenase type 1. AB - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the interconversion of inert glucocorticoid (cortisone) to the active glucocorticoid (cortisol) and is enriched in liver and fat tissues. Increasing evidence suggests that selective inhibition of 11beta-HSD1 may reduce the excess glucocorticoid levels that underlie the etiology of many common disorders that constitute the metabolic syndrome. Measurement of 11beta-HSD1 activity has historically involved the detection of cortisol by methods unfavorable for large-scale screening, such as high performance liquid chromatography or thin layer chromatography. Here we describe the development and validation of novel homogeneous time-resolved fluorescence resonance energy transfer (TR-FRET) and electrochemiluminescence assays for the measurement of cortisol. These non-radioactive assays were easy to perform and produced robust results with reference compound values comparable to those obtained by conventional methods. The TR-FRET assay was easily automated and was successfully employed for the high-throughput screening of a large compound library for inhibitors of purified human recombinant 11beta-HSD1. PMID- 17355204 TI - Ultra-high-throughput screening for antagonists of a Gi-coupled receptor in a 2.2 microl 3,456-well plate format cyclicAMP assay. AB - 3',5'-Cyclic adenosine monophosphate (cAMP) is a common intracellular second messenger that enables cells to respond to external stimuli. Measurement of intracellular cAMP concentrations is thus widely used for studying guanosine triphosphate binding protein-coupled receptors (GPCRs), which make up a large class of pharmaceutical drug targets. Although several assay technologies exist to measure cAMP, most are not suitable for ultra-high-throughput screening (uHTS), as is often required for screening large (greater than 1 million) chemical libraries for the identification of suitable leads for drug development. Here we report that the enzyme fragment complementation assay, a homogeneous gain of signal assay based on complementation of two fragments of a beta-galactosidase enzyme, is compatible with uHTS requirements of a 2.2-microl total assay volume in 3,456-well plate format. We describe the miniaturization of this assay into 3,456-well plate format exhibiting comparable sensitivity and plate statistics to those of a 384-well assay and the application of this assay in uHTS for the identification of antagonists of a Gi-coupled receptor. PMID- 17355205 TI - Bioluminescent assays for high-throughput screening. AB - In the development of high throughput screening (HTS) as a central paradigm of drug discovery, fluorescence has generally been adopted as the favored methodology. Nevertheless, luminescence has maintained a prominent position among certain assay formats, most notably genetic reporters. Recently, there has been growing partiality for luminescent assays across a wider range of applications due to their sensitivity, broad linearity, and robustness to library compounds and complex biological samples. This trend has been fostered by the development of several new assay designs for diverse targets such as kinases, cytochrome p450s, proteases, apoptosis, and cytotoxicity. This review addresses recent progress made in the use of bioluminescent assays for HTS, highlighting new detection capabilities brought about by engineering luciferase genes, enzymes, and substrates. In genetic reporter applications, modifications to the luciferase genes have improved assay sensitivity by substantially increasing expression efficiency and enhanced response dynamics by reducing expression lifetime. The performance of assays based on detection of ATP and luciferin has been enhanced by modifications to the luciferase enzyme that increase its chemical and physical stability. Detection of ATP allows rapid analysis of cell metabolism and enzymatic processes coupled to ATP metabolism. Because luciferins are not naturally associated with mammalian physiology, assays for luciferin detection utilize synthetic derivatives designed to yield luminescence only when coupled with specific target enzymes. Finally, new methods for modulating the specific activity of luciferases are leading to the development of intracellular biosensors for dynamic detection of physiological processes. PMID- 17355206 TI - Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. AB - Many cell-based assays interrogating cell pathway activation employ protocols that require microscopic imaging techniques. However, such assays are not in general widely adopted for primary screening. Protein complementation, particularly of enzymes, provides an alternative approach for cell pathway analysis, with a principal advantage that is amenable to high throughput screening using microtiter plate protocols. Notably, alpha complementation of the enzyme beta-galactosidase has been exploited as a technology in this regard, using substrates that generates luminescent signals. This review describes the various uses of this flexible technology to cell-based assay development. PMID- 17355208 TI - Heterobifunctional poly(ethylene glycol)-tethered bone morphogenetic protein-2 stimulated bone marrow mesenchymal stromal cell differentiation and osteogenesis. AB - We describe a biomimetic mode of insoluble signaling stimulation to provide target delivery of bone morphogenetic protein-2 (BMP-2), with the aim of prolonging the retention of BMP-2 use in bone tissue engineering and to enable its localized release in response to cellular activity. In our novel localization process, we used heterobifunctional acrylate-N-hydroxysuccinimide poly(ethylene glycol) (PEG) as a spacer to tether BMP-2 onto a poly(lactide-co-glycolide) scaffold. Use of PEG-tethered BMP-2 was feasible because BMP-2 retained its activity after covalent conjugation. The PEG-tethered BMP-2 conjugate sustained stimulation and retained its mitogenic activity, notably affecting pluripotent stem cell proliferation and differentiation. We seeded the scaffolds with bone marrow-derived mesenchymal stromal cells as progenitor cells to evaluate their morphology and phenotypic expression. We also created bilateral, full-thickness cranial defects in rabbits to investigate the osteogenic effect of cultured mesenchymal stromal cells on bone regeneration in vivo. Histomorphometry and histology demonstrated that the PEG-tethered BMP-2 conjugate enhanced de novo bone formation after surgery. Our work revealed the potential for biomimetic surface engineering by entrapping signaling growth factor to stimulate osteogenesis. Our technique may provide a new platform for bone-engineered stem cell therapies. PMID- 17355210 TI - Transgene expression level and inherent differences in target gene activation determine the rate and fate of neurogenin3-mediated islet cell differentiation in vitro. AB - A significant challenge in many areas of tissue engineering is a readily available source of cells. One approach to address this challenge is to direct the differentiation of expandable stem or progenitor cells or the transdifferentiation of an already differentiated cell type to the desired cell type. A variety of methods have been explored for directing cell differentiation, including the ectopic expression of transcriptional factors that are known to influence cell differentiation during development. One such transcription factor, neurogenin3 (Ngn3), plays a critical role in islet cell development in vivo. Ectopic expression of Ngn3 in various cell types has previously been shown to promote differentiation toward islet cell phenotypes, but the overall efficiency of this differentiation and the specific islet cell type produced vary widely between reports. The present work evaluates the hypotheses that cellular response is determined by (1) differentiation status of the starting cell, (2) basal expression of other transcriptional factors, and (3) level of ectopic Ngn3 expression. Retroviral vectors were used to express Ngn3 in primary adult pancreatic ductal epithelial cells (PDEC), embryonic and adult stem cells (ESC and ASC), and transformed mouse pancreatic adenocarcinoma (mPAC) cells in vitro. Changes in phenotypes were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR), gene arrays, and immunohistochemistry. When Ngn3 was ectopically expressed in mouse and rat PDEC, downstream transcription factors (e.g., NeuroD, Nkx2.2, Isl-1) and endocrine hormones (most notably, ghrelin and somatostatin) were highly upregulated in a dose-dependent manner. In comparison to mPAC and mouse embryonic stem cells (mESC), PDEC displayed higher expression of most islet markers after normalization to Ngn3 levels. Differences in the basal expression and activation of transcription factors (e.g., Pax4, Pax6, and Nkx6.1) were observed between cell types, suggesting a mechanism by which precursors might preferentially generate different islet cell types. PMID- 17355211 TI - Treatment of Staphylococcus aureus infections: new issues, emerging therapies and future directions. AB - Infections due to Staphylococcus aureus are a major cause of morbidity and mortality worldwide. Antimicrobial resistance in strains of S. aureus is a continually evolving problem, including widespread methicillin resistance in hospitals, increasing methicillin resistance in community strains, and the recent acquisition of glycopeptide resistance. New antimicrobials with activity against S. aureus have recently entered the market or are in the late stages of development. In addition, there has been significant interest in the development of novel and immune-based strategies for prevention or treatment of S. aureus infections. This review describes established and emerging therapies for S. aureus infections, and considers the safety profiles and likely impact on present treatment standards of novel agents either undergoing clinical development or emerging onto the market. PMID- 17355212 TI - Problems and emerging approaches in HIV/AIDS vaccine development. AB - According to recent estimates, 39.5 million people have been infected with HIV and 2.9 million have already died. The effect of HIV infection on individuals and communities is socially and economically devastating. Although antiretroviral drugs have had a dramatically beneficial impact on HIV-infected individuals who have access to treatment, it has had a negligible impact on the global epidemic. Therefore, the need for an efficacious HIV/AIDS vaccine remains the highest priority of the world HIV/AIDS agenda. The generation of a vaccine against HIV/AIDS has turned out to be extremely challenging, as indicated by > 20 years of unsuccessful attempts. This review discusses the major challenges in the field and key experimental evidence providing a rationale for the use of non-structural HIV proteins, such as Rev, Tat and Nef, either in the native form or expressed by viral vectors such as a replicating adeno-vector. These non-structural proteins alone or in combination with modified structural HIV-1 Env proteins represent a novel strategy for both preventative and therapeutic HIV/AIDS vaccine development. PMID- 17355213 TI - Emerging drugs to treat Crohn's disease. AB - The advent of the anti-TNF agent infliximab has dramatically changed our concept of treating refractory inflammatory bowel disease, particularly Crohn's disease. Although infliximab has proven to induce clinical response and remission with rapid onset of mucosal healing, to spare steroids, to improve perianal disease and to increase quality of life, there is an ongoing debate about optimizing infliximab therapy and a clear unmet medical need for patients losing their response to this agent. Novel anti-TNF agents, mostly more humanized monoclonal antibodies, with subcutaneous administration, have shown efficacy and are in advanced stages of clinical development. Compounds targeted at alternative pathways in the immune cascade are not expected to enter the market soon. Promising novel therapeutic classes include the anti-IL-12/23 and anti-IFN-gamma agents and the selective adhesion molecule inhibitors. Most of the biologic therapies, including anti-TNF agents, are aimed at crucial pathways in the immune system on the crossroads between immune pathology and host defense. Therefore, long-term benefit to risk profiles need to be established for all novel drugs. PMID- 17355214 TI - Emerging drugs in lung transplantation. AB - The balance between immunosuppression to ensure graft tolerance while preventing emergence of infectious complications is key in lung transplantation. Although opportunistic infection may appear to be the most important of these complications, malignancies and severe drug toxicities significantly affect the short- and long-term outcomes of the patients. The present practice is combination therapy using drugs with complementary immunosuppressive action, to achieve synergistic immunosuppression with the lowest possible toxicity. Components of immunosuppression include induction and maintenance regimens. Primary graft failure remains an important cause of mortality and morbidity in the immediate post-transplant period. Acute rejection is a common complication after lung transplant, but responds well to augmented immunosuppression and immunomodulation. Chronic rejection still is the major cause of mortality in patients who survive the initial year post-transplantation. Several new drugs have shown promise in decreasing the rate of loss of graft function. This review discusses the current and emerging therapeutic regimens. PMID- 17355215 TI - Emerging drugs for acute and chronic heart failure: current and future developments. AB - Heart failure continues to be a major public health issue. Although angiotensin converting enzyme inhibitors and beta-adrenergic blockers have been broadly used as evidence-based therapies in heart failure, morbidity and mortality remains high. Furthermore, treatment for acute decompensated heart failure and diastolic heart failure (or 'heart failure with preserved ejection fraction') is far from perfect. This review provides a broad overview of some of the novel compounds under investigation for the treatment of heart failure. Novel strategies include drugs that aim to alleviate congestion and improve hemodynamics, drugs that preserve renal function, drugs that reduce arterial and myocardial stiffness, drugs that module myocardial contractility, drugs that affect metabolic and hormonal balance, and drugs that act on existing and novel physiologic targets. PMID- 17355216 TI - Advances in ischemic stroke treatment: neuroprotective and combination therapies. AB - Thrombolysis with intravenous alteplase (recombinant tissue-type plasminogen activator) continues to be the sole recourse for acute ischemic stroke therapy, provided that patients seek treatment preferably within 3 h of stroke onset. The narrow window of efficacy, coupled with the significant risk of hemorrhage and the high mortality rate, preclude the use of alteplase beyond this time frame. Moreover, in part because of safety concerns, only a small percentage (6-15%) of eligible patients is treated with alteplase. Clearly, safer and more effective treatments that focus on improving the shortcomings of the present thrombolysis for stroke need to be identified. Therefore, newer thrombolytics are being developed with the goal of minimizing side effects, while also shortening the time of cerebral reperfusion and extending the therapeutic window of efficacy. Besides thrombolytics, new and potentially useful drugs and devices are also being studied either as monotherapeutic agents or for use in conjunction with alteplase. In animal models of stroke, neuroprotective agents that affect various components of the ischemic injury cascade that results in neurodegeneration have shown promise for the latter. Examples of such agents include spin traps that block oxidative stress, metalloprotease inhibitors that prevent vascular damage, anti-inflammatory drugs that suppress inflammation and transcranial infrared laser irradiation, which promotes recovery of function. Ideally, a successful combination of neuroprotectant (drug or device) and thrombolytic therapy for stroke would minimize the side effects of thrombolysis followed by supplementary neuroprotection thereafter. PMID- 17355217 TI - Emerging drugs in neuropathic pain. AB - Neuropathic pain is a personally devastating and costly condition affecting 3-8% of the population. Existing treatments have limited effectiveness and produce relatively frequent adverse effects. Preclinical research has identified many promising pharmacological targets; however, reliable predictors of success in humans remain elusive. At least 50 new molecular entities have reached clinical development including: glutamate antagonists, cytokine inhibitors, vanilloid receptor agonists, catecholamine modulators, ion-channel blockers, anticonvulsants, opioids, cannabinoids, COX inhibitors, acteylcholine modulators, adenosine receptor agonists and several miscellaneous drugs. Eight drugs are in Phase III trials at present. Strategies that may show promise over existing treatments include topical therapies, analgesic combinations and, in future, gene related therapies. Recent years have heralded an explosion of pharmaceutical development in neuropathic pain, reflecting advanced knowledge of neurobiology and a heightened perception of the commercial value of neuropathic pain therapeutics. In the interest of improving patient care, the authors recommend implementing comparative studies throughout the development process in order to demonstrate the increased value of novel agents. PMID- 17355218 TI - Emerging drugs for mesothelioma. AB - Malignant mesothelioma is an aggressive, but relatively rare, malignancy, affecting the pleura and peritoneum. The prognosis for malignant pleural mesothelioma (MPM) is poor, with median survival in the range of 8-14 months, depending on stage and presentation of disease. Long-term results of available treatments are disappointing not only in terms of prognosis, but also of local control of the disease. Therefore, relief of symptoms and improvement of quality of life parameters are the short-term goals of therapy. In advanced disease not amenable to any local approach, such as surgery, combination chemotherapy represents the current standard of care. At present, the regimen of cisplatin/pemetrexed is the medical treatment of choice. This review summarizes standard chemotherapy options and focuses on the molecular basis of the newest biologically targeted therapies to be implemented in the near future, in the management of MPM. PMID- 17355219 TI - Emerging drugs for the treatment of soft tissue sarcomas. AB - Soft tissue sarcomas are rare cancers of mesenchymal origin. Recent progress in the understanding of the biology of these rare tumours has enabled the identification of distinct molecular and pathological entities within this heterogenous group of neoplasms, and has paved the way for the development of targeted therapeutics directed against activated kinases. One of the most clear examples is the identification of KIT and platelet-derived growth factor receptor alpha kinase mutations in gastrointestinal stromal tumours, a subset of sarcomas arising from precursors of the interstitial cells of Cajal in the digestive tract, which led to the development of imatinib, sunitinib and other tyrosine kinase inhibitors for the treatment of solid tumours. This model has become the paradigm of a targeted treatment of solid tumours designed to inhibit the causal alteration in the oncogenesis of these tumours. This review summarises treatment strategies in the context of advanced disease and discusses new compounds being developed for patients with soft tissue sarcomas. PMID- 17355220 TI - Emerging drugs in multiple myeloma. AB - The treatment of multiple myeloma has seen significant changes from the time of the initial use of cytotoxic agents such as melphalan, to the introduction of high-dose chemotherapy and stem cell transplantation, and most recently the era of novel targeted agents. These new drugs have rapidly become the mainstay of therapy of this disease and transformed the treatment paradigm, leading to improvements in survival and quality of life. Existing therapeutic options include agents such as thalidomide, bortezomib and lenalidomide, either used alone or in combination with standard agents, including glucocorticoids, and in conjunction with high-dose chemotherapy supported with stem cell transplantation. Several other targeted agents have demonstrated exciting preclinical activity, and are presently being tested in early Phase I and II clinical trials. This review summarizes the role of novel therapeutic agents in multiple myeloma, and the promising effect of multiple new agents in development. PMID- 17355221 TI - Emerging therapeutic options for Philadelphia-positive acute lymphocytic leukemia. AB - Acute lymphocytic leukemia (ALL) is a heterogeneous group of disorders that are associated with a cure rate of > 80% in children. The prognosis in adults is considerably inferior, with age, disease bulk, leukemia karyotype and immune phenotype being prognostically relevant. Adult ALL treatment programs include induction, intensified consolidation and maintenance phases with CNS prophylaxis. The addition of imatinib in patients with BCR-ABL-positive ALL has improved the prognosis of this subgroup, but their survival is still poor. Initial data on the second-generation BCR-ABL inhibitors, dasatinib and nilotinib, indicate a potentially greater efficacy than imatinib, but the improvement is likely to be modest. The overall efforts in terms of developmental therapeutics in ALL are very modest and not in keeping with the urgent need for improvement. Most agents being investigated have mechanisms of action similar to those of existing agents for ALL therapy and thus represent modest opportunities to improve results. Of such agents, data on BCR-ABL inhibitors, sphingosomal vincristine, pemetrexed, talotrexin, annamycin and ABT-751 are reviewed. PMID- 17355222 TI - Autophosphorylation-dependent degradation of Pak1, triggered by the Rho-family GTPase, Chp. AB - The Paks (p21-activated kinases) Pak1, Pak2 and Pak3 are among the most studied effectors of the Rho-family GTPases, Rac, Cdc42 (cell division cycle 42) and Chp (Cdc42 homologous protein). Pak kinases influence a variety of cellular functions, but the process of Pak down-regulation, following activation, is poorly understood. In the present study, we describe for the first time a negative-inhibitory loop generated by the small Rho-GTPases Cdc42 and Chp, resulting in Pak1 inhibition. Upon overexpression of Chp, we unexpectedly observed a T-cell migration phenotype consistent with Paks inhibition. In line with this observation, overexpression of either Chp or Cdc42 caused a marked reduction in the level of Pak1 protein in a number of different cell lines. Chp induced degradation was accompanied by ubiquitination of Pak1, and was dependent on the proteasome. The susceptibility of Pak1 to Chp-induced degradation depended on its p21-binding domain, kinase activity and a number of Pak1 autophosphorylation sites, whereas the PIX- (Pak-interacting exchange factor) and Nck-binding sites were not required. Together, these results implicate Chp induced kinase autophosphorylation in the degradation of Pak1. The N-terminal domain of Chp was found to be required for Chp-induced degradation, although not for Pak1 activation, suggesting that Chp provides a second function, distinct from kinase activation, to trigger Pak degradation. Collectively, our results demonstrate a novel mechanism of signal termination mediated by the Rho-family GTPases Chp and Cdc42, which results in ubiquitin-mediated degradation of one of their direct effectors, Pak1. PMID- 17355223 TI - PPARalpha and AP-2alpha regulate bombesin receptor subtype 3 expression in ozone stressed bronchial epithelial cells. AB - Previously, we found that bombesin receptor subtype 3 (BRS-3) significantly increased in an ozone-stressed airway hyperresponsiveness animal model and resulted in induced wound repair and protection from acute lung injury. In the present study, we determined molecular mechanisms of BRS-3 regulation in human BECs (bronchial epithelial cells) in response to ozone stress. Ten oligonucleotide probes corresponding to various regions of the BRS-3 promoter were used in EMSA (electrophoretic mobilityshift assays). Four were found to have an enhanced mobility shift with extracts from ozone-stressed cells. On the basis of the assay of mutated probes binding with extracts and antibody supershift, they were verified as MTF-1 (metal-regulatory-element-binding transcription factor-1), PPARalpha (peroxisome-proliferator-activated receptor alpha), AP 2alpha (activator protein 2alpha) and HSF-1 (heat-shock factor 1). Next, ChIP (chromatin immunoprecipitation) assay, site-directed mutagenesis technology and antisense oligonucleotide technology were used to observe these transcription factors associated with the BRS-3 promoter. Only AP-2alpha and PPARalpha increased ozone-inducible DNA binding on the BRS-3 promoter and BRS-3 expression. The time courses of AP-2alpha and PPARalpha activation, followed by BRS-3 expression, were also examined. It was shown that ozone-inducible BRS-3 expression and AP-2alpha- and PPARalpha-binding activity correlated over a 48 h period. The translocation of PPARalpha was observed by immunofluorescence assay, which showed that PPARalpha nuclear translocation increased after ozone exposure. Our data suggest that AP-2alpha and PPARalpha may be especially involved in this ozone-inducible up-regulation mechanism of BRS-3 expression. PMID- 17355224 TI - Were inefficient mitochondrial haplogroups selected during migrations of modern humans? A test using modular kinetic analysis of coupling in mitochondria from cybrid cell lines. AB - We introduce a general test of the bioenergetic importance of mtDNA (mitochondrial DNA) variants: modular kinetic analysis of oxidative phosphorylation in mitochondria from cybrid cells with constant nuclear DNA but different mtDNA. We have applied this test to the hypothesis [Ruiz-Pesini, Mishmar, Brandon, Procaccio and Wallace (2004) Science 303, 223-226] that particular mtDNA haplogroups (specific combinations of polymorphisms) that cause lowered coupling efficiency, leading to generation of less ATP and more heat, were positively selected during radiations of modern humans into colder climates. Contrary to the predictions of this hypothesis, mitochondria from Arctic haplogroups had similar or even greater coupling efficiency than mitochondria from tropical haplogroups. PMID- 17355225 TI - A new strategy to inhibit the excision reaction catalysed by HIV-1 reverse transcriptase: compounds that compete with the template-primer. AB - Inhibitors of the excision reaction catalysed by HIV-1 RT (reverse transcriptase) represent a promising approach in the fight against HIV, because these molecules would interfere with the main mechanism of resistance of this enzyme towards chain-terminating nucleotides. Only a limited number of compounds have been demonstrated to inhibit this reaction to date, including NNRTIs (non-nucleoside RT inhibitors) and certain pyrophosphate analogues. We have found previously that 2GP (2-O-galloylpunicalin), an antiviral compound extracted from the leaves of Terminalia triflora, was able to inhibit both the RT and the RNase H activities of HIV-1 RT without affecting cell proliferation or viability. In the present study, we show that 2GP also inhibited the ATP- and PP(i)-dependent phosphorolysis catalysed by wild-type and AZT (3'-azido-3'-deoxythymidine) resistant enzymes at sub-micromolar concentrations. Kinetic and direct-binding analysis showed that 2GP was a non-competitive inhibitor against the nucleotide substrate, whereas it competed with the binding of RT to the template-primer (K(d)=85 nM). As expected from its mechanism of action, 2GP was active against mutations conferring resistance to NNRTIs and AZT. The combination of AZT with 2GP was highly synergistic when tested in the presence of pyrophosphate, indicating that the inhibition of RT-catalysed phosphorolysis was responsible for the synergy found. Although other RT inhibitors that compete with the template primer have been described, this is the first demonstration that these compounds can be used to block the excision of chain terminating nucleotides, providing a rationale for their combination with nucleoside analogues. PMID- 17355228 TI - Class I and class II major histocompatibility complex genes in Mexican patients with actinic prurigo. PMID- 17355227 TI - Cellular gene transfer mediated by influenza virosomes with encapsulated plasmid DNA. AB - Reconstituted influenza virosomes (virus membrane envelopes) have been used previously to deliver pDNA (plasmid DNA) bound to their external surface to a variety of target cells. Although high transfection efficiencies can be obtained with these complexes in vitro, the virosome-associated DNA is readily accessible to nucleases and could therefore be prone to rapid degradation under in vivo conditions. In the present study, we show a new method for the production of DNA virosomes resulting in complete protection of the DNA from nucleases. This method relies on the use of the short-chain phospholipid DCPC (dicaproylphosphatidylcholine) for solubilization of the viral membrane. The solubilized viral membrane components are mixed with pDNA and cationic lipid. Reconstitution of the viral envelopes and simultaneous encapsulation of pDNA is achieved by removal of the DCPC from the mixture through dialysis. Analysis by linear sucrose density-gradient centrifugation revealed that protein, phospholipid and pDNA physically associated to particles, which appeared as vesicles with spike proteins inserted in their membranes when analysed by electron microscopy. The DNA-virosomes retained the membrane fusion properties of the native influenza virus. The virosome-associated pDNA was completely protected from degradation by nucleases, providing evidence for the DNA being highly condensed and encapsulated in the lumen of the virosomes. DNA-virosomes, containing reporter gene constructs, transfected a variety of cell lines, with efficiencies approaching 90%. Transfection was completely dependent on the fusogenic properties of the viral spike protein haemagglutinin. Thus, DNA virosomes prepared by the new procedure are highly efficient vehicles for DNA delivery, offering the advantage of complete DNA protection, which is especially important for future in vivo applications. PMID- 17355226 TI - The molecular structure of human tissue type XV presents a unique conformation among the collagens. AB - Establishing the structure of the non-fibrillar collagens has provided a unique perspective to understanding their specialized functions in the extracellular matrix. These proteins exhibit very diverse conformations and supramolecular assemblies. Type XV collagen is a large macromolecule distinguished by a highly interrupted collagenous domain and many utilized sites of attachment for CS (chondroitin sulfate) and HS (heparan sulfate) glycosaminoglycan chains. It is present in most basement membrane zones of human tissues, where it is found closely associated with large collagen fibrils. To determine the molecular shape and organization of type XV, the protein was purified from human umbilical cords by salt extraction, and by ion-exchange and antibody-affinity chromatography. The representation of type XV in one of its most abundant tissue sources is estimated at only (1-2)x10(-4)% of dry weight. The molecules examined by transmission electron microscopy after rotary shadowing were visualized in multiple forms. Relatively few type XV monomers appeared elongated and kinked; most molecules were found in a knot/figure-of-eight/pretzel configuration not previously described for a collagen. Collective measurements of these populations revealed an average length of 193+/-16 nm. At the N-terminal end, identified by C-terminal antibody binding, were three 7.7 nm-diameter spheres, corresponding to TSPN-1 (N terminal module of thrombospondin-1) modules, and attached to the collagen backbone by a short linker. The type XV monomers show the ability to self assemble into higher-order structures. Some were arranged in complex clusters, but simpler oligomers, which may represent intermediates, were observed in a cruciform pattern with intermolecular binding sites that probably originate in the interruption sequences. The morphology of type XV is thus the antithesis of the fibrillar collagens, and the shape attains the required flexibility to form the spectrum of interconnecting links between banded fibrils at the basement membrane/interstitial border. These type XV structures may act as a biological 'spring' to stabilize and enhance resilience to compressive and expansive forces, and the multimers, in particular, with selective complements of many localized CS and HS chains, may be instrumental in spatial and temporal recruitment of modulators in growth, development and pathological processes. PMID- 17355229 TI - Rituximab in the adjuvant treatment of pemphigus vulgaris: a prospective open label pilot study in five patients. AB - BACKGROUND: Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B lymphocytes. There are reports of its efficacy in the treatment of autoimmune diseases, including pemphigus. OBJECTIVES: Prospectively to evaluate the efficacy of rituximab as adjuvant treatment for pemphigus vulgaris (PV). METHODS: Patients with PV were treated with intravenous rituximab (375 mg m(-2)) weekly for 4 weeks in this prospective open-label pilot study. Other concurrent immunosuppression was continued. RESULTS: Of five patients, one achieved complete remission and was able to cease all medication, while two achieved clearance of clinical lesions but continued on systemic therapy. Two patients had progressive disease. Time to response was 2-8 months, with a 13- to 18-month response duration. Response was associated with reduction in serum antiepithelial antibodies. Two patients had significant infectious complications (one developed community-acquired pneumonia associated with delayed-onset neutropenia and the other developed cytomegalovirus infection). CONCLUSIONS: Rituximab has shown efficacy in the treatment of PV. Patients on multiple immunosuppressives should be closely monitored for infectious complications. PMID- 17355230 TI - Schnitzler syndrome: a case report of successful treatment using the anti-CD20 monoclonal antibody rituximab. PMID- 17355231 TI - An infant with extensive Mongolian spot, naevus flammeus and cutis marmorata telangiectatica congenita: a unique case of phakomatosis pigmentovascularis. PMID- 17355232 TI - Nail bed lichen planus associated with onychopapilloma. PMID- 17355233 TI - Olopatadine hydrochloride accelerates the recovery of skin barrier function in mice. AB - BACKGROUND: The skin barrier function in patients with atopic dermatitis is disrupted and prolonged topical steroid therapy produces epidermal barrier disturbance. Olopatadine hydrochloride (olopatadine; Allelock; Kyowa Hakko Kogyo Co., Ltd, Shizuoka, Japan) is an antiallergic drug with histamine H(1) receptor antagonistic action. This drug alleviates skin inflammation and decreases the number of scratching episodes in a murine model of chronic contact dermatitis. OBJECTIVES: To investigate the effects of olopatadine and a steroid on the recovery of skin barrier function after barrier disruption in mice. METHODS: The skin barrier of the ears of mice was disrupted by tape stripping. The recovery of skin barrier function was monitored by measurement of transepidermal water loss (TEWL) after barrier disruption. Epidermal hyperplasia was induced by repeated tape stripping for 7 days. Olopatadine was administered orally once daily from 3 days before the first barrier disruption. Betamethasone 17-valerate (betamethasone) was applied topically once daily from 3 days before barrier disruption. RESULTS: Tape stripping led to a significant increase in TEWL. TEWL decreased with time after tape stripping and the skin barrier function recovered by over 60% within 9 h after tape stripping. The recovery of skin barrier in olopatadine-treated mice was significantly accelerated, compared with that in vehicle-treated mice. In contrast, the skin barrier recovery in mice treated with topical betamethasone was significantly delayed, compared with that in vehicle treated mice. Combined treatment with olopatadine and betamethasone ameliorated the delay in barrier recovery induced by topical treatment with betamethasone. In addition, olopatadine significantly prevented the increase in epidermal thickness induced by prolonged barrier disruption. CONCLUSIONS: These results suggest that systemic administration of olopatadine accelerates the recovery of skin barrier function and ameliorates the adverse effects of topical steroids on skin barrier recovery. PMID- 17355234 TI - Effect of ultraviolet (UV) A, UVB or ionizing radiation on the cell cycle of human melanoma cells. AB - BACKGROUND: One important component of the cellular response to irradiation is the activation of cell cycle checkpoints. It is known that both ultraviolet (UV) radiation and ionizing radiation (IR) can activate checkpoints at transitions from G(1) to S phase, from G(2) phase to mitosis and during DNA replication. OBJECTIVES: To evaluate the effects of irradiation with different wavelengths on cell cycle alterations. METHODS: p53-deficient IPC-298 melanoma cells were irradiated with 10 J cm(-2) UVA, 40 mJ cm(-2) UVB, or with 7.5 Gy IR. Cell cycle effects were then determined by DNA/5-bromodeoxyuridine dual-parameter flow cytometry. RESULTS: IPC-298 cells irradiated in G(1) with UVA were not arrested at the G(1)/S transition, but at the G(2)/M transition. Despite p53 deficiency, the cells showed a G(1) arrest after UVB exposure. Furthermore, IR did not affect G(1) or S phase, but induced G(2) phase arrest. Hence, the effects of UVA, but not of UVB, on the cell cycle in p53-deficient melanoma cells are comparable with those of IR. CONCLUSIONS: UVA and IR induce radical-mediated strand breaks and DNA lesions, and UVB essentially induces thymine dimers that lead to excision repair-related strand breaks. Different cell cycle effects may be a consequence of different types of DNA damage. The results showed that UVB-irradiated p53 deficient cells are arrested in G(1). Irradiation with the solar radiation component UVB can therefore result in a beneficial retardation of tumour promotion in human skin carrying p53-mutated cell clones. PMID- 17355235 TI - Two patients with localized epidermolysis bullosa acquisita: diagnostic value of laser scanning confocal microscopy. PMID- 17355236 TI - Ultrastructural features of ichthyosis hystrix strongly resembling Lambert type. AB - Ichthyosis hystrix (IH) is characterized by spiny hyperkeratotic scale, and includes Brocq type, Lambert type, Curth-Macklin type, Rheydt type and Bafverstedt type. The first documented cases of familial IH were of Lambert type. However, the ultrastructural features of IH Lambert type have not been reported. Three patients in two generations of a family from north China were observed. The patients showed widespread verrucose lesions without blister formation. The face, palms and soles were unaffected. This presentation strongly resembled IH Lambert type. The lesions faded dramatically in summer, without treatment. Light microscopic examinations showed binuclear cells and shell formation in the granular and upper spinous layers in all specimens, with similar findings in winter, when lesions were prominent, and in summer, when lesions had subsided. Electron microscopic examination revealed binuclear keratinocytes and concentric, thin to thick, unbroken shells of tonofilaments surrounding the nuclei, and segregation of cytoplasmic components. This family is the first with familial IH strongly resembling Lambert type to be reported in China. Binuclear cells and tonofilaments shells surrounding the nucleus in upper keratinocytes were characteristic features, which were similar to those reported in IH Curth-Macklin type. The basic histopathological defects were not changed despite significant clinical improvement of the lesion. PMID- 17355237 TI - Should we discard the graft? Analysis of the renal grafts with a total ischemia time of more than 24 hours donated after cardiac death. AB - The objective is to investigate the outcome of transplantation using kidney grafts from donors after cardiac death (DCDs) with a total ischemia time (TIT) longer than 24 h. All 373 kidneys were procured from DCDs. They were procured using the in-situ regional cooling technique. Grafts were classified into two groups according to TIT. Fifty-three grafts had a TIT longer than 24 h (group 1), and the other 320 grafts (group 2) were less than 24 h. The numbers of never functioning grafts (PGF) were 3 in group 1 (5.7%) and 17 in group 2 (5.3%), a nonsignificant difference. Graft survival rates at 3, 5 and 10 years posttransplant were 84.9%, 73.0% and 64.1% in group 1, and 76.3%, 69.9% and 57.1% in group 2, which demonstrate no significant difference. The significant risk factors for graft failure were donor age, serum creatinine level on hospitalization and WIT. However, TIT longer than 24 h was not employed. Multivariate logistic regression indicated that only WIT was associated with an increase in the risk of PGF. Our results demonstrate that kidneys from DCDs, even if their TIT is more than 24 h, should be considered a worthwhile source of renal grafts. PMID- 17355238 TI - Chronic renal failure in kidney transplant recipients. Do they receive optimum care?: data from the UK renal registry. AB - We report the prevalence of chronic kidney disease (CKD) and related complications in a national cohort of RTR (n=9542), and compare this with dialysis patients. The majority of RTR were classified as having CKD stage 2T (21.6%) or 3T (57.5%) with 15.7% classified as CKD stage 4T and 3.1% as stage 5T. Only 2.1% of RTR were in CKD stage 1T. The proportion of patients with stage 4T and 5T CKD who lost their graft in the following year was 8% and 49%, respectively. The prevalence of anemia (hemoglobin <11 g/dL) increased from 4.4% in stage 1T to 51.5% in stage 5T and compared with 30% in dialysis patients (p<0.0001). Hypertension, hyperphosphatemia, elevated Ca x PO(4), raised iPTH and hypoalbuminemia rose with increasing CKD stage. For many variables, the achievement of standards was lower in stage 5T RTR than in dialysis patients. There were center differences in median estimated glomerular filtration rate and percentage of patients with hemoglobin <11 g/dL (p<0.0001). In conclusion, many patients in stage 4T-5T have CKD-related complications that fall below targets established for nontransplant CKD patients. They are at increased risk of graft loss. More attention needs to be paid to managing these complications and preparing these patients for a return to dialysis and/or retransplantation. PMID- 17355239 TI - Indirect recognition of T-cell epitopes derived from the alpha 3 and transmembrane domain of HLA-A2. AB - Indirect allorecognition has been implicated in the mechanism of chronic rejection and alloantibody formation but precise definition of the epitopes involved has been limited. We have undertaken a detailed assessment of the antigenic properties of peptides derived from HLA-A2. Candidate epitopes were identified in vitro by assessment of MHC class II binding. The immune response to these epitopes was determined in patients awaiting a renal transplant by the assessment of PBMC activation using gamma-interferon ELISPOT. Twenty-two of fifty five patients responded to peptides from HLA-A2 and this was associated with but not confined to those who had made antibody to HLA-A2 (14/18). Nineteen of twenty two patients responded to peptides derived from the hypervariable alpha1 and alpha2 domains and 18/22 responded to peptides from the alpha 3 and transmembrane domain, the sequences of which show little polymorphism. In six patients, the sequence of these peptides was identical to self, that is, the response was autoimmune. The finding of indirect epitopes derived from regions of MHC class I that exhibit little polymorphism provides a novel perspective on the immune response to alloantigen and has potential implications for the development of specific therapies. PMID- 17355240 TI - Tyrosine phosphorylation of a 38-kDa capacitation-associated buffalo (Bubalus bubalis) sperm protein is induced by L-arginine and regulated through a cAMP/PKA independent pathway. AB - The aim of the present study was to determine the effect of L-arginine on nitric oxide (NO*) synthesis, capacitation and protein tyrosine phosphorylation in buffalo spermatozoa. Ejaculated buffalo spermatozoa were capacitated in the absence or presence of heparin, or L-arginine or N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS) for 6 h. Capacitating spermatozoa generated NO* both spontaneously and following stimulation with L arginine and L-NAME quenched such L-arginine-induced NO* production. Immunolocalization of NOS suggested for existence of constitutive NOS in buffalo spermatozoa. L-Arginine (10 mm) was found to be a potent capacitating agent and addition of L-NAME to the incubation media attenuated both L-arginine and heparin induced capacitation and suggested that NO* is involved in the capacitation of buffalo spermatozoa. Two sperm proteins of M(r) 38 000 (p38) and 20 000 (p20) were tyrosine phosphorylated extensively by both heparin and L-arginine. Of these, the tyrosine phosphorylation of p38 was insensitive to both induction by cAMP agonists as well as inhibition by a protein kinase A (PKA) inhibitor. Further, most of these L-arginine-induced tyrosine phosphorylated proteins were localized to the midpiece and principal piece regions of flagellum of capacitated spermatozoa and suggested that sperm flagellum takes active part during capacitation. These results indicated that L-arginine induces capacitation of buffalo spermatozoa through NO* synthesis and tyrosine phosphorylation of specific sperm proteins involving a pathway independent of cAMP/PKA. PMID- 17355241 TI - Leptin receptor in boar spermatozoa. AB - Leptin is active in both metabolism and reproduction. In fact, it seems to exert an inhibitory action on gonadal functions by reducing testosterone production. The presence of leptin in human and boar seminal plasma and in human spermatozoa has been demonstrated; recently, leptin receptors (Ob-R) have been localized in human spermatozoa, thus suggesting a possible action of this hormone even on these cells. Our aim was to verify whether leptin receptor [the long form (Ob Rb)] is present in boar spermatozoa. Immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR) techniques were employed. RNA was extracted from boar spermatozoa and a specific band (382 bp) for Ob-Rb was detected after RT-PCR. Ob-Rb was detected on acrosome, subequatorial area and either on the midpiece or on the whole tail. These localizations were maintained even in semen washed twice to eliminate seminal plasma. We conclude that Ob-R is present in boar spermatozoa where seminal plasma leptin can exert its effects. PMID- 17355242 TI - IgE and atopy in perinatally HIV-infected children. AB - Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens. PMID- 17355243 TI - At diabetes-like concentration, glucose down-regulates the placental serotonin transport system in a cell-cycle-dependent manner. AB - Serotonin [5-hydroxytryptamine (5HT)] is a vasoconstrictor that also acts as a developmental signal early in embryogenesis. The 5HT transporter (SERT) on the membranes of the placental trophoblast cells controls 5HT levels in the maternal bloodstream to maintain stable transplacental blood flow and simultaneously provide 5HT to the embryo. The 5HT uptake rate of placental SERT is important for both the mother and the developing embryo. The impact of glucose on the placental SERT system during diabetic pregnancy is not known. The present in vitro study investigated this important issue in human placental choriocarcinoma (JAR) cells that were cultured for 24-96 h in a medium containing either 5.5 (physiologic concentration) or 25 mmol/L D-glucose (diabetic-like concentration). The 5HT uptake rates of the cultured cells were not altered at exogenous D-glucose concentrations in the range of 5.5-15 mmol/L, but were decreased significantly at a diabetic-like concentration (>or=25 mmol/L). To understand better the role of glucose on the placental 5HT system, we first characterized SERT in JAR cells at different cell-cycle phases and then determined the expression levels of SERT on the plasma membrane and in the intracellular pools of JAR cells at the late-S and G2 phases, where the uptake rates were decreased 73% under diabetic-like glucose concentrations. Finally, the importance of self-association of SERT molecules was examined. In JAR cells co-expressing Flag- and myc-tagged SERT, myc-antibody precipitated 70% of Flag-SERT, indicating that a large percentage of SERT proteins exist as oligomers in situ. Under diabetic conditions, myc-antibody no longer precipitated Flag-SERT, suggesting a disruption in the aggregation of SERT molecules. Therefore, we propose that under uncontrolled diabetic conditions, glucose down-regulates 5HT uptake rates of placental SERT by interfering with its functional expression in a cell-cycle-dependent manner. PMID- 17355244 TI - Paediatric acute liver failure and transplantation: the University of Essen experience. AB - To report our experience with 17 children who underwent a liver transplantation (LT) for acute liver failure (ALF). All LT procedures (deceased and living donor) were offered. Since 2003 Molecular Adsorbents Recycling System (MARS) was proposed as bridging procedure. We monitored the perioperative course and the short- and long-term outcomes. All children developed pretransplant hepatic encephalopathy (mostly grades II and III); six needed ventilator support and three haemodialysis. Median PELD/MELD score was 30. MARS was used in five children with poor pretransplant prognostic factors: all five survived the LT without sequelae. We performed 13 deceased donor LT (seven whole, five split and onr reduced) and four left lateral LDLT. Postoperative complications were observed in 10 children, requiring re-operation in seven. Two children developed irreversible neurological disorders. After a median follow up of 45 months, 16 children are still alive. About 1- and 5-year cumulative patient survival rates are 94% with a corresponding graft survival of 88% and 81%, respectively. The combination of experienced paediatric ICU management, the application of new liver support devices, and the capacity to offer both living and deceased donor transplant alternatives in a timely fashion represent the best formula to achieve optimal results in children with ALF. PMID- 17355245 TI - An international opinion poll of well-educated people regarding awareness and feelings about organ donation for transplantation. AB - Despite repeated campaigns promoting transplantation, the high donation refusal rate remains unchanged. We targeted a well-educated population to assess the impact of our current transplantation promoting programs and personal feelings toward new approaches to organ donation. A questionnaire was proposed in five universities to students and university staffs that would have been likely to benefit from previous information campaigns in two South American and three European countries. All of the 2321 people interviewed replied to at least one question. Organ shortage was considered as a serious public health issue. However, there was a widespread ignorance of religious precepts concerning transplantation that contributed to the low acceptance rate of organ sharing after death. Financial rewards for donors or their families remain controversial. There was a general agreement for early educational programs in schools. Most people still consider organ donation as a gift, but many would now agree to readily share body parts after death. This biased population of well-educated people has still little knowledge of organ donation. The negative impact of ignorance surrounding religious precepts and the high acceptance rate of educational programs in schools, justify supporting an intensive international effort in education that should also include Church leaders. PMID- 17355246 TI - Influence of hypersulfated and low molecular weight heparins on ischemia/reperfusion: injury and allograft rejection in rat kidneys. AB - The aim of the study was to evaluate the effect of the hypersulfated nonanticoagulant heparin derivative LU 51198 (LU) and of the low molecular weight heparin reviparin (REVI) on ischemia/reperfusion (I/R) injury, acute rejection (AR) and chronic allograft nephropathy (CAN) in rats. Organs were harvested 5 days after 60 min of renal I/R injury. For investigation of AR and CAN we used the allogeneic Fisher-Lewis model. Kidneys were harvested at one respectively 32 weeks after transplantation. Rats were treated with either vehicle, LU or REVI. After I/R injury, treatment with REVI or LU reduced infiltration with MHC II and R73-positive cells, whereas only REVI reduced ED1-positive cells and expression of monocyte chemoattractant protein-1. There was no effect of REVI and LU on acute allograft rejection. Treatment with LU or REVI reduced glomerular infiltration with ED1 and MHCII-positive cells and renal expression of transforming growth factor-beta 32 weeks after transplantation. Only REVI treatment reduced albuminuria, interstitial infiltration and histological signs of CAN. LU, and in a more potent manner REVI, reduce signs of CAN and renal inflammation after I/R injury. Chemically modified heparins without anticoagulatory effects may offer a new treatment option in preventing I/R injury and CAN in human kidney transplantation. PMID- 17355247 TI - Effect of leptin on activation and cytokine synthesis in peripheral blood lymphocytes of malnourished infected children. AB - Malnutrition compromises immune function, resulting in reduced resistance to infection. Recent animal and human studies have suggested that leptin is capable of modulating the immune response and that its levels, which are regulated by nutritional status, fall rapidly during starvation. Leptin deficiency is associated with impaired cell-mediated immunity, an increased incidence of infectious disease and an associated increase in mortality. The purpose of this study was to examine the effect of leptin on activation and cytokine production in peripheral blood T cells from malnourished children. The data obtained in the present study demonstrate that leptin produced an increase in the percentage of CD4(+) and CD8(+) cells producing interleukin (IL)-2 and interferon (IFN)-gamma in 24-h cultures. Moreover, leptin decreased the percentage of CD4(+) and CD8(+) cells producing IL-4 and IL-10, and enhanced activation of circulating T cells when co-stimulated by phorbol 12-myristate 13 acetate (PMA)-ionomycin. Leptin enhanced the expression of activation markers CD69 and CD25 in both CD4(+) and CD8(+) cells after 5 h of stimulation. In conclusion, the results obtained show that leptin modulates CD4(+) and CD8(+) cell activation towards a T helper 1 (Th1) phenotype by stimulating the synthesis of IL-2 and IFN-gamma. In contrast, leptin decreases IL-4 and IL-10 production. Moreover, leptin enhanced the expression of CD69 and CD25 on CD4(+) and CD8(+) cells after stimulation with PMA ionomycin. PMID- 17355248 TI - Differential activation of NF-kappaB and gene expression in oral epithelial cells by periodontal pathogens. AB - To investigate the molecular effects of the periodontopathogens Fusobacterium nucleatum (FN) and Porphyromonas gingivalis (PG) on the oral epithelium, the H400 oral epithelial cell line was cultured in the presence of non-viable bacteria. Following confirmation of the presence of transcripts for the bacterial pattern recognition receptors in H400 cells, Toll-like receptors -2, -4 and -9, and components of the NF-kappaB signalling pathway, immunocytochemical analyses were performed showing that NF-kappaB was activated within 1 h of exposure to both periodontopathogens. A significantly greater number of NF-kappaB nuclear translocations were apparent following H400 cell exposure to FN as compared with PG. Gene expression analyses indicated that transcripts known to be regulated by the NF-kappaB pathway, including cytokines/chemokines TNF-alpha, IL-1beta, IL-8, MCP-1/CCL2 and GM-CSF, were up-regulated following 4 and 24 h of exposure to both periodontopathogens. In addition, H400 periodontopathogen exposure resulted in differential regulation of transcripts for several cytokeratin gene family members. Consistent with the immunocytochemical data, microarray results indicated that FN induced a greater number of gene expression changes than PG following 24 h of exposure, 609 and 409 genes, respectively. Ninety-one genes were commonly differentially expressed by both periodontopathogens and represented biological processes commonly associated with periodontitis. Gene expression analyses by reserve transcriptase-polymerase chain reaction (RT-PCR) of molecules identified from the microarray data sets, including Heme oxygenase 1, lysyl oxidase, SOD2, CCL20 and calprotectin components, confirmed their differential expression profiles induced by the two periodontopathogens. FN and PG have clearly different molecular effects on oral epithelial cells, potentially highlighting the importance of the composition of the plaque biofilm in periodontitis pathogenesis. PMID- 17355249 TI - Diminished forkhead box P3/CD25 double-positive T regulatory cells are associated with the increased nuclear factor-kappaB ligand (RANKL+) T cells in bone resorption lesion of periodontal disease. AB - Periodontal disease involves multi-bacterial infections accompanied by inflammatory bone resorption lesions. The abundant T and B lymphocyte infiltrates are the major sources of the osteoclast differentiation factor, receptor activator for nuclear factor-kappaB ligand (RANKL) which, in turn, contributes to the development of bone resorption in periodontal disease. In the present study, we found that the concentrations of RANKL and regulatory T cell (T(reg)) associated cytokine, interleukin (IL)-10, in the periodontal tissue homogenates were correlated negatively, whereas RANKL and proinflammatory cytokine, IL-1beta, showed positive correlation. Also, according to the fluorescent immunohistochemistry, the frequency of forkhead box P3 (FoxP3)/CD25 double positive cells was diminished strikingly in the bone resorption lesion of periodontal disease compared to healthy gingival tissue, while CD25 or FoxP3 single positive cells were still observed in lesions where abundant RANKL+ lymphocytes were present. Very importantly, few or no expressions of FoxP3 by the RANKL+ lymphocytes were observed in the diseased periodontal tissues. Finally, IL 10 suppressed both soluble RANKL (sRANKL) and membrane RANKL (mRANKL) expression by peripheral blood mononuclear cells (PBMC) activated in vitro in a bacterial antigen-specific manner. Taken together, these results suggested that FoxP3/CD25 double-positive T(reg) cells may play a role in the down-regulation of RANKL expression by activated lymphocytes in periodontal diseased tissues. This leads to the conclusion that the phenomenon of diminished CD25+FoxP3+ T(reg) cells appears to be associated with the increased RANKL+ T cells in the bone resorption lesion of periodontal disease. PMID- 17355250 TI - The synaptic vesicle proteome. AB - Synaptic vesicles are key organelles in neurotransmission. Vesicle integral or membrane-associated proteins mediate the various functions the organelle fulfills during its life cycle. These include organelle transport, interaction with the nerve terminal cytoskeleton, uptake and storage of low molecular weight constituents, and the regulated interaction with the pre-synaptic plasma membrane during exo- and endocytosis. Within the past two decades, converging work from several laboratories resulted in the molecular and functional characterization of the proteinaceous inventory of the synaptic vesicle compartment. However, up until recently and due to technical difficulties, it was impossible to screen the entire organelle thoroughly. Recent advances in membrane protein identification and mass spectrometry (MS) have dramatically promoted this field. A comparison of different techniques for elucidating the proteinaceous composition of synaptic vesicles revealed numerous overlaps but also remarkable differences in the protein constituents of the synaptic vesicle compartment, indicating that several protein separation techniques in combination with differing MS approaches are required to identify and characterize the synaptic vesicle proteome. This review highlights the power of various gel separation techniques and MS analyses for the characterization of the proteome of highly purified synaptic vesicles. Furthermore, the newly detected protein assignments to synaptic vesicles, especially those proteins which are new to the inventory of the synaptic vesicle proteome, are critically discussed. PMID- 17355251 TI - Primary vitrectomy versus conventional retinal detachment surgery in phakic rhegmatogenous retinal detachment. AB - PURPOSE: This study aimed to compare the results of primary vitrectomy and conventional scleral buckling procedures (conventional retinal detachment surgery) in phakic rhegmatogenous retinal detachment (RRD). METHODS: We carried out a randomized, prospective, clinical controlled trial of 61 consecutive phakic eyes with primary RRD, not complicated by proliferative vitreoretinopathy >or= grade C. Subjects were randomized to either scleral buckling (group 1) or pars plana vitrectomy (group 2). RESULTS: At 6 months follow-up, the primary reattachment rate was 80% (24/30 cases) in group 2 and 80.6% (25/31 cases) in group 1; the difference between the two groups was not statistically significant (p = 0.213). Best corrected visual acuity improved significantly from a preoperative median of 1.78 (1/60) (mean 1.73 +/- 0.91, range 0.3-3) to a median of 0.6 (6/24) (mean 0.689 +/- 0.35, range 0.18-1.48) in group 2 and from a preoperative median of 1.48 (2/60) (mean 1.43 +/- 0.92, range 0-3) to a median of 0.6 (6/24) (mean 0.608 +/- 0.36, range 0-1.78) in group 1; the difference between the two groups was not statistically significant (p = 0.376). Cataract developed in five cases (17%) in the vitrectomy group (group 2), with a statistically significant difference of p = 0.018. CONCLUSIONS: Although primary vitrectomy can achieve anatomical and functional success rates comparable with those achieved by scleral buckling in uncomplicated forms of phakic RRD, the major drawback of the procedure is the high incidence of postoperative cataract formation. Moreover, visual rehabilitation takes place earlier with scleral buckling than with vitrectomy. Scleral buckling should thus be used as the primary surgical modality in the treatment of uncomplicated RRD where the media are sufficiently clear. PMID- 17355252 TI - Activation of hippocampal postsynaptic muscarinic receptors is involved in long term spatial memory formation. AB - Spatial memory has been strongly associated with hippocampal function. There are several reports of the participation of this structure in acquisition and consolidation of spatial tasks. In this study, we evaluated the effects of selective and non-selective muscarinic antagonists in the dorsal hippocampus of rats during acquisition and encoding of a spatial task. Rats were trained in a Morris water maze for 4 days with identical daily sessions, and tested for long term memory (LTM) 1 week after training. The animals were injected bilaterally in the dorsal hippocampus 20 min before the start of every day of training. The results showed that the non-selective muscarinic antagonist, scopolamine, disrupted acquisition of water maze memory formation. Moreover, microinjections of a selective postsynaptic muscarinic antagonist, pirenzepine, disrupted LTM, whereas it did not affect acquisition. Conversely, a selective presynaptic muscarinic antagonist, AFDX-116, did not disrupt either water maze acquisition or LTM formation. Combination of AFDX-116 and pirenzepine had similar effects as scopolamine, partially blocking acquisition and impairing long-term spatial memory. These results support the view that muscarinic receptors are involved in spatial learning and that postsynaptic muscarinic receptors in the dorsal hippocampus are particularly involved in long-term spatial memory formation. PMID- 17355253 TI - Neurotrophins modulate neuron-glia interactions at a vertebrate synapse. AB - Neurotrophins are important modulators of synaptic function at both developing and mature synapses in the CNS and PNS. At the neuromuscular junction (NMJ), neurotrophins, as well as perisynaptic Schwann cells (PSCs) are critical for the long-term maintenance and stability of the synapse. Considering this correlation and the acute interactions that occur at the synapse between PSCs and the nerve terminal, we wondered if neurotrophins could also be involved in neuron-glia signalling. To test if neurotrophins were able to signal to PSCs we used brief applications of neurotrophin-3 (NT-3), brain-derived neurotophic factor (BDNF) or nerve growth factor (NGF; 100 ng/mL). Soleus muscles of mice were incubated with the Ca(2+) indicator Fluo-4AM and Ca(2+) responses in PSCs were elicited through nerve stimulation (50 Hz, 30 s). Our results indicate that acute application of both NT-3 and BDNF, but not NGF, increased PSC Ca(2+) responses. Investigation of the mechanisms involved in these increases revealed distinct pathways for BDNF and NT-3. BDNF increased PSC responsiveness through potentiation of ATP responses while NT-3 modulated muscarinic acetylcholine receptor signalling. Using local applications of the neurotrophins, we found that both neurotrophins were able to elicit Ca(2+) responses in PSCs where BDNF used a phospholipase C-inositol 1,4,5 triphosphate (PLC-IP(3)) mechanism, while NT-3 required extracellular Ca(2+). Our results demonstrate a neurotrophin-dependent modulation of neuron-glia signalling through differential mechanisms employed by NT-3 and BDNF. Hence, neurotrophins precisely and differentially regulate PSC functions through modulation of either purinergic or cholinergic signalling pathways. PMID- 17355254 TI - Complete or partial hippocampal damage produces equivalent retrograde amnesia for remote contextual fear memories. AB - We examined the effects of partial or complete damage to the hippocampus on long term retention of a Pavlovian conditioned fear response to context. Rats received a single contextual fear-conditioning episode and 1 week, 3 months or 6 months later they received sham, partial (dorsal) or complete NMDA-induced damage of the hippocampus. During a retention test conducted 2 weeks after surgery, the control rats exhibited high levels of freezing in the context, although their level of freezing was significantly lower with longer retention intervals. Rats with complete hippocampal damage displayed very little freezing in the context at each learning-surgery interval. Partial hippocampal damage caused a smaller but consistent deficit in conditioned responding, especially at longer learning surgery intervals. Neither group of hippocampus-damaged rats showed less retrograde amnesia for more remote memories. We found that the severity of retrograde amnesia for contextual fear conditioning following hippocampal damage is related to the extent of the damage and that there is consistent and severe retrograde amnesia for even remote contextual fear memories. These findings support the idea that the hippocampal formation has an essential and long lasting, possibly permanent, role in memory for contexts. PMID- 17355255 TI - Spontaneous haemoperitoneum caused by inferior pancreaticoduodenal artery aneurysm rupture: case report. PMID- 17355257 TI - The unique pharmacology of the scorpion alpha-like toxin Lqh3 is associated with its flexible C-tail. AB - The affinity of scorpion alpha-toxins for various voltage-gated sodium channels (Na(v)s) differs considerably despite similar structures and activities. It has been proposed that key bioactive residues of the five-residue-turn (residues 8 12) and the C-tail form the NC domain, whose topology is dictated by a cis or trans peptide-bond conformation between residues 9 and 10, which correlates with the potency on insect or mammalian Na(v)s. We examined this hypothesis using Lqh3, an alpha-like toxin from Leiurus quinquestriatus hebraeus that is highly active in insects and mammalian brain. Lqh3 exhibits slower association kinetics to Na(v)s compared with other alpha-toxins and its binding to insect Na(v)s is pH dependent. Mutagenesis of Lqh3 revealed a bi-partite bioactive surface, composed of the Core and NC domains, as found in other alpha-toxins. Yet, substitutions at the five-residue turn and stabilization of the 9-10 bond in the cis conformation did not affect the activity. However, substitution of hydrogen-bond donors/acceptors at the NC domain reduced the pH-dependency of toxin binding, while retaining its high potency at Drosophila Na(v)s expressed in Xenopus oocytes. Based on these results and the conformational flexibility and rearrangement of intramolecular hydrogen-bonds at the NC domain, evident from the known solution structure, we suggest that acidic pH or specific mutations at the NC domain favor toxin conformations with high affinity for the receptor by stabilizing the bound toxin-receptor complex. Moreover, the C-tail flexibility may account for the slower association rates and suggests a novel mechanism of dynamic conformer selection during toxin binding, enabling alpha-like toxins to affect a broad range of Na(v)s. PMID- 17355258 TI - Selective detection of superoxide anion radicals generated from macrophages by using a novel fluorescent probe. AB - Quantitation of superoxide radical (O (2)(-).) production at the site of radical generation remains challenging. A simple method to detect nanomolar to micromolar levels of superoxide radical in aqueous solution has been developed and optimized. This method is based on the efficient trapping of O(2)(-). using a novel fluorescent probe (2-chloro-1,3-dibenzothiazolinecyclohexene), coupled with a spectra character-signaling increase event. A high-specificity and high sensitivity fluorescent probe was synthesized in-house and used to image O(2)(-). in living cells. Better selectivity for O(2)(-). over competing cellular reactive oxygen species and some biological compounds illustrates the advantages of our method. Under optimal conditions, the linear calibration range for superoxide anion radicals was 5.03 x 10(-9)-3.33 x 10(-6) M. The detection limit was 1.68 x 10(-9) M. Fluorescence images of probe-stained macrophages stimulated with 4beta phorbol 12-myristate 13-acetate were obtained successfully using a confocal laser scanning microscope. PMID- 17355259 TI - Meningeal recurrence of intravascular large B-cell lymphoma: early diagnosis with PET-CT. PMID- 17355260 TI - Aplastic anaemia as an autoimmune complication of thymoma. PMID- 17355261 TI - Inhibition of ADAM17 reduces hypoxia-induced brain tumor cell invasiveness. AB - The membrane-anchored metalloproteinase tumor necrosis factor-alpha-converting enzyme (TACE/a disintegrin and metalloproteinase [ADAM] 17) is key in proteolytic ectodomain shedding of several membrane-bound growth factors, cytokines and receptors. The expression and activity of ADAM17 increases under some pathological conditions including stroke, and promotes neural progenitor cell migration and contributes to stroke-induced neurogenesis. Hypoxia initiates cellular invasive processes that occur under both physiological and pathological conditions such as invasion and metastasis of some tumors. In the present study, we sought to elucidate whether ADAM17 contributes to brain tumor invasion. To this end, we examined the role of ADAM17 in the invasiveness of two different brain tumor cell lines, 9L rat gliosarcoma and U87 human glioma, under normoxic and hypoxic conditions. Additionally, we tested the effects of ADAM17 suppression on in vitro tumor cell invasion by means of ADAM17 proteolytic inhibitors and specific small interfering RNA. We found that tumor cells upregulated ADAM17 expression under hypoxia, and that ADAM17 activity correlated with increased tumor cell invasion. Conversely, suppression of ADAM17 proteolysis decreased invasiveness induced by hypoxia in 9L and U87 cells. Furthermore, the contribution of ADAM17 to tumor invasion was independent of matrix metalloproteinase (MMP)-2 and MMP-9 activity. ADAM17 was also found to activate the epidermal growth factor/phosphoinositide-3 kinase/serine/threonine kinase signal transduction pathway. Our data suggest that hypoxia-induced ADAM17 contributes to glioma cell invasiveness through activation of the EGFR signal pathway. PMID- 17355262 TI - Critical role of estrogen receptor on anoikis and invasion of squamous cell carcinoma. AB - Estrogen receptor (ER) plays an important role in various physiological functions. We examined whether ERalpha and ERbeta are expressed in squamous cell carcinoma (SCC), and whether ER is a potential target for antitumor therapy. High level expression of ERbeta, but not ERalpha, was observed in tumor cells of human primary SCC tissues and various SCC cultured cell lines. Treatment with ER antagonist (tamoxifen), but not agonist (estradiol), caused apoptotic cell death of SCC cells in a concentration- and time-dependent manner. Adhesion of SCC was inhibited by the treatment with tamoxifen, but not with estradiol. Tamoxifen reduced the phosphorylation of focal adhesion kinase (FAK), resulting in decreases in phosphorylation of extracellular signal-related kinase (Erk) and mitogen-activated protein kinase. Inhibition of FAK phosphorylation is accompanied by disorder of the cytoskeletal component actin. The cell death caused by tamoxifen is therefore the result of direct interference in cell adhesion, which is called 'anoikis', involving a decrease in intracellular FAK signaling. Expression of epidermal growth factor receptor was also inhibited by treatment with a high concentration of tamoxifen. Knockdown of ERbeta by small interfering RNA inhibited the proliferation of SCC. In addition, tamoxifen strongly inhibited invasion of SCC. These results imply a potentially important role for ER, whose inhibition may be effective for the treatment of SCC and the prevention of invasion and metastasis. PMID- 17355263 TI - Polymorphisms in the DNA repair gene XRCC1 associated with basal cell carcinoma and squamous cell carcinoma of the skin in a Korean population. AB - DNA in most cells is regularly damaged by endogenous and exogenous mutagens. Unrepaired damage can result in apoptosis or may lead to unregulated cell growth and cancer. Inheritance of genetic variants at one or more loci results in reduced DNA repair capacity. This hospital-based case-control study examined whether polymorphisms in the DNA repair gene X-ray repair cross-complementing groups 1 (XRCC1) (Arg194Trp[C > T], Arg280His[G > A] and Arg399Gln[G > A]) play a role in susceptibility to skin cancer. We genotyped these polymorphisms for 212 histopathologically confirmed skin cancer cases (n = 114 basal cell carcinoma, n = 98 squamous cell carcinoma) and 207 age- and sex-matched healthy control cases in Korea. We found that individuals with the Arg/Gln and Arg/Gln + Gln/Gln genotypes at XRCC1 Arg399Gln(G > A) had an approximately 2-fold increased risk of basal cell carcinoma compared to individuals with the Arg/Arg genotype (adjusted odds ratio [AOR] = 2.812, 95% confidence interval [CI] 1.32-5.98, and AOR = 2.324, 95% CI 1.11-4.86). However, we observed that the 194Trp allele of the Arg194Trp(C > T) polymorphism was inversely associated with squamous cell carcinoma risk (Trp/Trp, AOR = 0.06, 95% CI 0.006-0.63). Our data suggest that the Arg194Trp and Arg399Gln polymorphisms may be differentially associated with skin cancer risk. PMID- 17355264 TI - Predictive value of GADD153, p21 and c-Jun for chemotherapy response in gastric cancer. AB - We sought to determine whether changes in the expression of early response genes (GADD153, p21 and c-Jun) are indicators of chemotherapy response in gastric cancer. Three human gastric cancer cell lines were exposed to 5-fluorouracil or cisplatin in vitro. Xenografts of TMK-1 cells in nude mice were also treated with 5-fluorouracil or cisplatin in vivo. For each of these treatments, we tested for a correlation between early gene expression levels and inhibition ratios derived at a later time. A 5-fluorouracil derivative, S-1, and cisplatin were administered to 12 patients with advanced gastric cancer for 3 weeks. Gene expression levels were measured using biopsy specimens obtained by endoscopy soon after initiation of chemotherapy. There was a significant correlation between expression levels of these genes at 24 h and inhibition ratios at 72 h in vitro. Cut-off values determined from receiver-operating characteristic curves were 1.3 for GADD153, 1.8 for p21 and 2.1 for c-Jun There was also a significant correlation between gene expression levels at 2 days and inhibition ratios at 21 days in vivo. Cut-off values were 1.8 for GADD153, 1.9 for p21 and 2.2 for c-Jun. Levels of early response gene expression in patients showing progressive disease were significantly lower than those in patients with partial response. Changes in the expression of the three early response genes soon after drug administration could improve predictions of the final outcome of chemotherapy in gastric cancer. PMID- 17355265 TI - ADAMs in cancer cell proliferation and progression. AB - A disintegrin and metalloproteinases (ADAMs) are a new gene family of proteins with sequence similarity to the reprolysin family of snake venomases that share the metalloproteinase domain with matrix metalloproteinases (MMPs). They are structurally classified into two groups: the membrane-anchored ADAM and ADAM with thrombospondin motifs (ADAMTS). These molecules are involved in various biological events such as cell adhesion, cell fusion, cell migration, membrane protein shedding and proteolysis. Studies on the biochemical characteristics and biological functions of ADAMs are in progress, and accumulated lines of evidence have shown that some ADAMs are expressed in malignant tumors and participate in the pathology of cancers. The activities of ADAMs are regulated by gene expression, intracytoplasmic and pericellular regulation, activation of the zymogens and inhibition of activities by inhibitors. Many ADAM species, including ADAM8, ADAM9, ADAM10, ADAM12, ADAM15, ADAM17, ADAM19, ADAM28, ADAMTS1, ADAMTS4 and ADAMTS5, are expressed in human malignant tumors. Many of them are involved in the regulation of growth factor activities and integrin functions, leading to promotion of cell growth and invasion, although the precise mechanisms of these are not clear at the present time. In this article, we review recent information about ADAM family members and their implications for cancer cell proliferation and progression. PMID- 17355266 TI - Cancer patients' distresses and inquiries: proposal of four-level classification based on consultation service and questionnaire survey. AB - The present study was undertaken to understand the realities of cancer patients' and their family members' distresses and inquiries, including medical/physical, emotional/spiritual and social/economic problems, from scientific viewpoints. The initial step of the study was to develop the classification category for these distresses and inquiries. The category was proposed based on information from two different sources; one is the consultation records of the Patient Support and Inquiry Division, Shizuoka Cancer Center and the other is the database of the Questionnaire Survey, which consisted of more than 25,000 distresses from 7885 people who faced up to cancer. The four-level classification category was constructed from 16 primary categories, 35 secondary categories, 129 tertiary categories and 619 quaternary categories. The classification category made it possible to analyze the distresses of cancer patients and their family members. The present study demonstrated the differences between the patterns of distresses for the consultation service and the questionnaire survey. In consultation centers belonging to hospitals, such as the Patient Support and Inquiry Division in the Shizuoka Cancer Center, patients wanted to consult on distresses and inquiries related to medical care. In contrast, they rarely consulted on emotional/spiritual or social problems. Based on the present classification category, we are developing a database called 'Questions and Answers for Cancer Patients' Distresses'. The database enables medical staff to learn what distresses patients and their family members, and to implement high-quality consultation in cancer clinics. PMID- 17355267 TI - Association of caesarean delivery for first birth with placenta praevia and placental abruption in second pregnancy. AB - OBJECTIVE: To quantify the risk of placenta praevia and placental abruption in singleton, second pregnancies after a caesarean delivery of the first pregnancy. DESIGN: Retrospective cohort study. SETTING: Linked birth and infant mortality database of the USA between 1995 and 2000. POPULATION: A total of 5,146,742 singleton second pregnancies were available for the final analysis after excluding missing information. METHODS: Multiple logistic regressions were used to describe the relationship between caesarean section at first birth and placenta praevia and placental abruption in second-birth singletons. MAIN OUTCOME MEASURES: Placenta praevia and placental abruption. RESULTS: Placenta praevia was recorded in 4.4 per 1000 second-birth singletons whose first births delivered by caesarean section and 2.7 per 1000 second-birth singletons whose first births delivered vaginally. About 6.8 per 1000 births were complicated with placental abruption in second-birth singletons whose first births delivered by caesarean section and 4.8 per 1000 birth in second-birth singletons whose first births delivered vaginally. The adjusted odds ratio (95% CIs) of previous caesarean section for placenta praevia in following second pregnancies was 1.47 (1.41, 1.52) after controlling for maternal age, race, education, marital status, maternal drinking and smoking during pregnancy, adequacy of prenatal care, and fetal gender. The corresponding figure for placental abruption was 1.40 (1.36, 1.45). CONCLUSION: Caesarean section for first live birth is associated with a 47% increased risk of placenta praevia and 40% increased risk of placental abruption in second pregnancy with a singleton. PMID- 17355268 TI - Does hormone replacement therapy affect the use of prescription medicines in postmenopausal women: experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757]. AB - OBJECTIVE: To determine how postmenopausal hormone therapy (HRT) is related to the use of other prescription medication. DESIGN: Follow up of a randomised controlled trial with a blind subtrial of hormone therapy versus placebo and a nonblind subtrial of open label hormone therapy versus nontreatment. POPULATION: A total of 1823 postmenopausal women aged 50-64 at the time of sampling participated in the trial from 1999 to 2004. METHODS: Use of prescription medication was identified by records in the central computerised database of the Estonian Health Insurance Fund. MAIN OUTCOME MEASURES: The use of 21 classes of prescription medication was compared in the hormone therapy arms and placebo or nontreatment trial arms. The influence of women's socio-economic characteristics on the intensity of concomitant medication use was also examined. RESULTS: The proportion of women using any prescription medication besides hormone therapy did not differ between the arms. However, the type of prescribed drugs varied between the arms. After combining data from both hormone therapy arms, for women using HRT the combined hazard ratio was 1.26 (95% CI: 1.05-1.53) for the use of calcium channel blockers, 1.48 (95% CI: 1.10-1.99) for local vaginal treatment, 0.70 (95% CI: 0.50-0.99) for hypnotics and sedatives and 0.77 (95% CI: 0.60-0.99) for selective serotonin reuptake inhibitors (SSRIs). Women who were older, who had a higher body mass index, who were unemployed and who lived outside the capital used more prescription drugs in comparison with others. CONCLUSIONS: Hormone therapy did not increase the overall use of prescription medication other than hormone therapy, but the types of drugs used in hormone therapy and nontherapy arms varied, with increased use of calcium channel blockers for hypertension and local vaginal treatments for vaginal candidiasis and decreased use of hypnotics, sedatives and SSRIs in the HRT arms. PMID- 17355269 TI - Termination of pregnancy for fetal anomaly: a population-based study 1995 to 2004. AB - Terminations of pregnancy for fetal anomaly (TOPFAs) were analysed over a 10-year period from a population-based congenital anomaly register covering 646,342 births. A total of 3189 cases of TOPFA were identified, prevalence of 49.3 per 10,000 registerable births. The rate of TOPFA at all gestations and at less than 16 weeks increased significantly. There were 102 cases of liveborn TOPFAs (3.2%). The proportion of liveborn TOPFAs after 22 weeks of gestation decreased significantly but below 22 weeks remains unchanged. TOPFA is increasing in frequency, occurring earlier in pregnancy. Live birth is a possible important outcome. PMID- 17355270 TI - The complications of external cephalic version: results from 805 consecutive attempts. AB - Most breech babies at term are now delivered by caesarean section. Although external cephalic version reduces the number of term breech presentations, its uptake has not been as wide as is recommended by professional bodies. This may be because of fears over safety. Pooled safety data do exist, largely from case series. However, the possibility of reporting and publication biases in such studies maybe preventing both women and obstetricians from being adequately reassured. In this series of 805 consecutive version attempts, we report an extremely low complication rate and 0.5% risk of emergency caesarean section after the procedure. PMID- 17355271 TI - Monitoring obstetricians' performance with statistical process control charts. AB - OBJECTIVE: The main objective of this study was to pave the way towards proactive, continuous assessment of individuals and hospitals by demonstrating the application of evidence-based competency standards in maternity care using statistical performance monitoring. DESIGN: Retrospective study using data routinely collected by a large maternity hospital. SETTING: A large teaching hospital. POPULATION: Clinicians who routinely perform either amniocentesis or ventouse deliveries. METHOD: As a 'proof of principle', we have used statistical process control (SPC) charts to compare the observed complication rates for amniocentesis and ventouse delivery with the expected complication rates based on published data. MAIN OUTCOME MEASURES: The recorded complication rates for amniocentesis and ventouse delivery. RESULTS: The SPC charts identified significant variation in complication rates within the team and showed the ways in which prospective data can be used to provide continuous feedback to individuals on their performance. CONCLUSION: The study shows that statistical performance monitoring and, in particular, the use of control charts can be a valuable tool in the continuous assessment of individuals and the healthcare service being provided. The control charts provide a more immediate indication of current performance and provide an alternative to performance-based league tables for the presentation of yearly performance data. PMID- 17355272 TI - Myeloid sarcoma of liver: an unusual cause of jaundice. Report of three cases and review of literature. PMID- 17355273 TI - Obstructive colitis and ischaemic colonic diverticula: two sides of one stricture. PMID- 17355274 TI - Giant cell-rich solitary fibrous tumour of the gallbladder. First case report. PMID- 17355275 TI - Poorly differentiated synovial sarcoma of the vagina: first reported case with immunohistochemical, molecular and ultrastructural data. PMID- 17355276 TI - Ureteric obstruction due to prostatic implantation in the sigmoid colon: a unique late complication of ureterosigmoidostomy. PMID- 17355277 TI - Pemphigus and associated environmental factors: a case-control study. AB - BACKGROUND: Recent reports have revealed the relatively high incidence of pemphigus in Iran. Occupational exposure and personal habits have been suggested to play a role in the aetiopathogenesis of this life-threatening disease. AIM: In order to analyse the association of environmental factors with pemphigus, we conducted a case-control study to evaluate the possible role of smoking, pesticide exposure and hormonal factors in Iran. METHODS: This study was conducted in Iran using a structured questionnaire. Questions included information on patients' smoking habits, occupational exposure to pesticides, use of oral contraception (OC) and number of pregnancies. RESULTS: We enrolled 210 patients with pemphigus and 205 control subjects. Fewer of patients with pemphigus (17.1%) reported a current or past history of smoking, which was statistically different from the control group (27.3% smokers). The duration of smoking and the number of cigarettes smoked daily was also significantly lower in patients. Although OC use was significantly higher in women with pemphigus, the mean number of pregnancies was not different between the two groups. Occupational exposure to pesticides was significantly higher in patients with pemphigus (14.8%) than in controls (5.4%); patients with pemphigus were exposed to pesticides three times more often than were healthy subjects. CONCLUSION: As a positive history of smoking was lower in patients with pemphigus compared with healthy subjects, it seems that smoking is a protective factor in pemphigus. This should encourage further investigations, searching for novel therapies. If pesticides and OC are confirmed as triggering factors, their cessation might reduce the need for pharmacological therapy. PMID- 17355278 TI - Hypertrophic pseudofolliculitis in white renal transplant recipients. AB - Renal transplant recipients (RTRs) are susceptible to many cutaneous disorders, including drug-induced skin changes. Hypertrichosis, sebaceous hyperplasia and gingival hyperplasia are well-recognized effects of ciclosporin, one of the immunosuppressants commonly used in RTRs. Pseudofolliculitis barbae usually affects hair-bearing areas of skin in men with darkly pigmented skin who shave on a regular basis. We describe five cases of hyperplastic pseudofolliculitis occurring in white RTRs taking ciclosporin as part of their immunosuppressive regimen. All five had involvement of the chin, the classic site of pseudofolliculitis barbae, and two had additional psuedofolliculitis of the nose or occiput. PMID- 17355279 TI - Stellate hypopigmented macules and papules on photoexposed areas. PMID- 17355280 TI - Acquired cold urticaria: clinical picture and update on diagnosis and treatment. AB - Acquired cold urticaria (ACU) is a frequent subtype of physical urticaria that is caused by the release of proinflammatory mast cell mediators after cold exposure. Although the underlying causes of ACU still remain to be clarified in detail, a wide range of diseases has been reported to be associated with ACU. This review gives an overview of the clinical picture, the differential diagnoses, diagnostic tests and the aetiology of ACU, and summarizes current and novel therapeutic options based on the current literature. PMID- 17355281 TI - Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. AB - OBJECTIVES: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Many medications have been used to prevent this complication. We aimed to evaluate the efficacy of rectally administered indomethacin for the prevention of post-ERCP pancreatitis. METHODS: During 18 months, all eligible patients who underwent ERCP were enrolled in this study. In a double-blind randomized trial, patients received a suppository containing indomethacin, 100 mg, or an inert placebo immediately before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. RESULTS: A total of 490 patients entered the trial, of which half received indomethacin. Twenty-two patients developed pancreatitis; seven cases in the indomethacin group and 15 in the placebo group (P=0.06). Pancreatic duct injection (OR=3.0, 95% CI: 1.3-7.4), pancreatic duct cannulation more than once (OR=4.2, 95% CI: 1.7-10.0), and age less than 60 yr (OR=2.7, 95% CI: 1.0 7.1) were shown to be significant risk factors for developing post-ERCP pancreatitis. In patients who underwent pancreatography with or without cholangiography, the risk of pancreatitis was significantly lower in the indomethacin group compared with the control group (P=0.01, RRR=88%, ARR=0.16, NNT=6). Moderate to severe pancreatitis was significantly higher in the placebo group (P= 0.03). CONCLUSIONS: This trial shows that rectal indomethacin given immediately before ERCP can reduce the incidence and severity of post-ERCP pancreatitis. PMID- 17355282 TI - A dideoxynucleotide-sensitive DNA polymerase activity characterized from endoreduplicating cells of mungbean (Vigna radiata L.) during ontogeny of cotyledons. AB - Within this work we describe the purification and biochemical characterization of a ddNTP-sensitive DNA polymerase purified from mungbean (Vigna radiata cv B1, L.) seeds at 18 days after fertilization, when > 70% of the nuclei are reported to be in the endoreduplicated state. The purified enzyme is a single polypeptide of 62 kDa and many of its physicochemical properties are similar to those of mammalian DNA polymerase beta. Similar to the other X-family DNA polymerases, it lacks 3' 5' exonuclease activity and has short gap-filling and strand-displacement activity. The enzyme shows moderately processive DNA synthesis on a single-strand template. The determined N-terminal heptapeptide sequence of the enzyme showed clear homology with helix 1 of the N-terminal single strand DNA-binding domain (residues 32-41) of rat and human DNA polymerase beta. These results represent the first evidence for the identification and characterization of a ddNTP sensitive DNA polymerase expressed during the endoreduplication cycle that shares biochemical and immunological similarity with mammalian DNA polymerase beta. PMID- 17355283 TI - The role of Ureaplasma nucleoside monophosphate kinases in the synthesis of nucleoside triphosphates. AB - Mollicutes are wall-less bacteria and cause various diseases in humans, animals and plants. They have the smallest genomes with low G + C content and lack many genes of DNA, RNA and protein precursor biosynthesis. Nucleoside diphosphate kinase (NDK), a house-keeping enzyme that plays a critical role in the synthesis of nucleic acids precursors, i.e. NTPs and dNTPs, is absent in all the Mollicutes genomes sequenced to date. Therefore, it would be of interest to know how Mollicutes synthesize dNTPs/NTPs without NDK. To answer this question, nucleoside monophosphate kinases (NMPKs) from Ureaplasma were studied regarding their role in the synthesis of NTPs/dNTPs. In this work, Ureaplasma adenylate kinase, cytidylate kinase, uridylate kinase and thymidylate kinase were cloned and expressed in Escherichia coli. The recombinant enzymes were purified and characterized. These NMPKs are base specific, as indicated by their names, and capable of converting (d)NMPs directly to (d)NTPs. The catalytic rates of (d)NTPs and (d)NDP synthesis by these NMPKs were determined using tritium-labelled (d)NMPs, and the rates for (d)NDP synthesis, in general, were much higher (up to 100-fold) than that of (d)NTP. Equilibrium studies with adenylate kinase suggested that the rates of NTPs/dNTPs synthesis by NMPKs in vivo are probably regulated by the levels of (d)NMPs. These results strongly indicate that NMPKs could substitute the NDK function in vivo. PMID- 17355284 TI - Expression and functional characterization of P2Y1 and P2Y12 nucleotide receptors in long-term serum-deprived glioma C6 cells. AB - We characterized the expression and functional properties of the ADP-sensitive P2Y(1) and P2Y(12) nucleotide receptors in glioma C6 cells cultured in medium devoid of serum for up to 96 h. During this long-term serum starvation, cell morphology changed from fibroblast-like flat to round, the adhesion pattern changed, cell-cycle arrest was induced, extracellular signal-regulated kinase (ERK1/2) phosphorylation was reduced, Akt phosphorylation was enhanced, and expression of the P2Y(12) receptor relative to P2Y(1) was increased. These processes did not reflect differentiation into astrocytes or oligodendrocytes, as expression of glial fibrillary acidic protein and NG2 proteoglycan (standard markers of glial cell differentiation) was not increased during the serum deprivation. Transfer of the cells into fresh medium containing 10% fetal bovine serum reversed the changes. This demonstrates that serum starvation caused only temporary growth arrest of the glioma C6 cells, which were ready for rapid division as soon as the environment became more favorable. In cells starved for 72 and 96 h, expression of the P2Y(1) receptor was low, and the P2Y(12) receptor was the major player, responsible for ADP-evoked signal transduction. The P2Y(12) receptor activated ERK1/2 kinase phosphorylation (a known cell proliferation regulator) and stimulated Akt activity. These effects were reduced by AR C69931MX, a specific antagonist of the P2Y(12) receptor. On the other hand, Akt phosphorylation increased in parallel with the low expression of the P2Y(1) receptor, indicating the inhibitory role of P2Y(1) in Akt pathway signaling. The shift in nucleotide receptor expression from P2Y(1) to P2Y(12) would appear to be a new and important self-regulating mechanism that promotes cell growth rather than differentiation and is a defense mechanism against effects of serum deprivation. PMID- 17355285 TI - Cleavage site analysis of a serralysin-like protease, PrtA, from an insect pathogen Photorhabdus luminescens and development of a highly sensitive and specific substrate. AB - The aim of this study was the development of a sensitive and specific substrate for protease A (PrtA), a serralysin-like metzincin from the entomopathogenic microorganism, Photorhabdus. First, cleavage of three biological peptides, the A and B chains of insulin and beta-lipotropin, and of 15 synthetic peptides, was investigated. In the biological peptides, a preference for the hydrophobic residues Ala, Leu and Val was observed at three substrate positions, P2, P1' and P2'. At these positions in the synthetic peptides the preferred residues were Val, Ala and Val, respectively. They contributed to the efficiency of hydrolysis in the order P1' > P2 > P2'. Six amino acids of the synthetic peptides were sufficient to reach the maximum rate of hydrolysis, in accordance with the ability of PrtA to cleave three amino acids from both the N- and the C-terminus of some fragments of biological peptides. Using the best synthetic peptide, a fluorescence-quenched substrate, N-(4-[4'(dimethylamino)phenylazo]benzoyl-EVYAVES 5-[(2-aminoethyl)amino]naphthalene-1-sulfonic acid, was prepared. The approximately 4 x 10(6) M(-1) x s(-1) specificity constant of PrtA (at K(m) approximately 5 x 10(-5) M and k(cat) approximately 2 x 10(2) s(-1)) on this substrate was the highest activity for a serralysin-type enzyme, allowing precise measurement of the effects of several inhibitors and pH on PrtA activity. These showed the characteristics of a metalloenzyme and a wide range of optimum pH, similar to other serralysins. PrtA activity could be measured in biological samples (Photorhabdus-infected insect larvae) without interference from other enzymes, which indicates that substrate selectivity is high towards PrtA. The substrate sensitivity allowed early (14 h post infection) detection of PrtA, which might indicate PrtA's participation in the establishment of infection and not only, as it has been supposed, in bioconversion. PMID- 17355286 TI - Mechanisms of cholinesterase inhibition by inorganic mercury. AB - The poorly known mechanism of inhibition of cholinesterases by inorganic mercury (HgCl2) has been studied with a view to using these enzymes as biomarkers or as biological components of biosensors to survey polluted areas. The inhibition of a variety of cholinesterases by HgCl2 was investigated by kinetic studies, X-ray crystallography, and dynamic light scattering. Our results show that when a free sensitive sulfhydryl group is present in the enzyme, as in Torpedo californica acetylcholinesterase, inhibition is irreversible and follows pseudo-first-order kinetics that are completed within 1 h in the micromolar range. When the free sulfhydryl group is not sensitive to mercury (Drosophila melanogaster acetylcholinesterase and human butyrylcholinesterase) or is otherwise absent (Electrophorus electricus acetylcholinesterase), then inhibition occurs in the millimolar range. Inhibition follows a slow binding model, with successive binding of two mercury ions to the enzyme surface. Binding of mercury ions has several consequences: reversible inhibition, enzyme denaturation, and protein aggregation, protecting the enzyme from denaturation. Mercury-induced inactivation of cholinesterases is thus a rather complex process. Our results indicate that among the various cholinesterases that we have studied, only Torpedo californica acetylcholinesterase is suitable for mercury detection using biosensors, and that a careful study of cholinesterase inhibition in a species is a prerequisite before using it as a biomarker to survey mercury in the environment. PMID- 17355287 TI - A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast. AB - In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue of Saccharomyces cerevisiae GABA aminotransferase, and SkPYD4 encodes an enzyme involved in both BAL and GABA transamination. SkPYD4 and SkUGA1 as well as S. cerevisiae UGA1 and Schizosaccharomyces pombe UGA1 were subcloned, over-expressed and purified. One discontinuous and two continuous coupled assays were used to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V(max)/K(m)=0.78 U x mg(-1) x mm(-1)), but can also use GABA (V(max)/K(m)=0.42 U x mg(-1) x mm(-1)), while SkUga1p only uses GABA (V(max)/K(m)=4.01 U x mg(-1) x mm(-1)). SpUga1p and ScUga1p transaminate only GABA and not BAL. While mammals degrade BAL and GABA with only one enzyme, but in different tissues, S. kluyveri and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication approximately 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity. PMID- 17355288 TI - Optical coherence tomography in anterior segment imaging. AB - PURPOSE: To evaluate the ability of optical coherence tomography (OCT), designed primarily to image the posterior segment, to visualize the anterior chamber angle (ACA) in patients with different angle configurations. METHODS: In a prospective observational study, the anterior segments of 26 eyes of 26 patients were imaged using the Zeiss Stratus OCT, model 3000. Imaging of the anterior segment was achieved by adjusting the focusing control on the Stratus OCT. A total of 16 patients had abnormal angle configurations including narrow or closed angles and plateau irides, and 10 had normal angle configurations as determined by prior full ophthalmic examination, including slit-lamp biomicroscopy and gonioscopy. RESULTS: In all cases, OCT provided high-resolution information regarding iris configuration. The ACA itself was clearly visualized in patients with narrow or closed angles, but not in patients with open angles. CONCLUSIONS: Stratus OCT offers a non-contact, convenient and rapid method of assessing the configuration of the anterior chamber. Despite its limitations, it may be of help during the routine clinical assessment and treatment of patients with glaucoma, particularly when gonioscopy is not possible or difficult to interpret. PMID- 17355289 TI - Neovascular membrane over the ciliary body as a potential complication of transscleral diode laser cyclophotocoagulation. PMID- 17355290 TI - Development of ankylosis in permanent incisors following delayed replantation and severe intrusion. AB - Ankylosis is a predictable outcome for replanted incisors and for most severely intruded incisors. There is no treatment to arrest or reverse this periodontal ligament complication. Ankylosis of the incisors of preadolescents alters local alveolar growth and eventually produces tooth loss subsequent to resorption. Currently, clinical methods used to diagnose ankylosis in the early postinjury period include subjective assessments of percussion sound and mobility and quantitative devices such as the Periotest. This paper describes the progression of ankylosis in two preadolescent patients that sustained severe trauma to their maxillary central incisors. A number of clinical assessments for diagnosis of ankylosis were compared for their usefulness, reliability and suitability. PMID- 17355291 TI - Dento-alveolar and maxillofacial injuries - a retrospective study from a level 1 trauma center in Israel. AB - To evaluate the frequency and causes of dental and maxillofacial trauma in hospitalized patients. From January 1, 2000 to December 31, 2003, data from hospitalized trauma patients in a level 1 trauma center in Israel were analyzed according to age, gender, time, place, and cause of injury. Maxillofacial and tooth injuries were separated and further analyzed according to the above parameters. The analysis was based on data from the Israel Trauma Registry (ITR). Of all 14 040 trauma patients, 1038 (7.4%) involved maxillofacial or dental injuries. Common causes of injury were motor vehicle crashes (41%), falls (27%) and intentional injuries (23%). Fifty percent occurred on the street/road, 17% at home and 14% in public buildings. Surgery was required in 55.5% of all maxillofacial injuries. Males were hospitalized three times more than females, and young people, ages 19-28, were at greatest risk (30.2%). Oral and maxillofacial trauma is common, requiring dental health training for primary caregivers. PMID- 17355293 TI - Childbirth in ancient Rome: from traditional folklore to obstetrics. AB - In ancient Rome, childbirth was a hazardous event for both mother and child with high rates of infant and maternal mortality. Traditional Roman medicine centred on folklore and religious practices, but with the development of Hippocratic medicine came significant advances in the care of women during pregnancy and confinement. Midwives or obstetrices played an important role and applied rational scientific practices to improve outcomes. This evolution from folklore to obstetrics was a pivotal point in the history of childbirth. PMID- 17355294 TI - Obstetric-induced incontinence: a black hole of preventable morbidity? An 'alternative' opinion. PMID- 17355295 TI - Pregnancy and Medicine: sine qua non or non sequitur? AB - Pregnancy is intrinsically imperfect, with high rates of complications for mothers and babies. A minority of pregnancies is entirely uncomplicated. Medical disorders are frequent contributors to morbidity for mothers and babies, and have become the major source of maternal mortality. For these reasons, Medicine plays a central role in the care of pregnant women. Provision of resources to maternity services must recognise the changing demographics and clinical characteristics of pregnant women in Australia, and their increased medical risk status in recent years. PMID- 17355296 TI - A survey of intrapartum fetal surveillance education practices in Victorian public hospitals. AB - BACKGROUND: The inappropriate use or interpretation of intrapartum fetal surveillance (IFS) continues to be a major contributor to adverse obstetric outcomes, suggesting that training in IFS is deficient. What professional education in intrapartum fetal surveillance currently exists in Victorian public hospitals is unknown. AIMS: To map the current formal IFS education and competency assessment practices in Victorian public hospitals. METHODS: A structured survey comprising 25 questions was developed and mailed to both a senior obstetric and a midwifery manager in all public maternity hospitals in Victoria. Non-respondents were followed up at 2 months. RESULTS: One hundred and twenty surveys were sent to 60 hospitals, of which 103 replies from 58 hospitals were received, representing a 97% hospital response rate. Only 19 (33%) of respondent hospitals had an existing education program. Hospitals with > 2000 births per annum were more likely to have a program than those with < 1000 births per annum (86% vs 23%, P=0.004). Of the 19 existing education programs, only nine contained any fetal physiology. All respondents thought that IFS education should be compulsory for relevant staff. Only six (10%) of the hospitals had any assessment of competency but 90% of respondents thought that such an assessment should be compulsory. CONCLUSIONS: These data reveal important deficiencies in the provision and quality of current IFS education practices in Victoria, particularly in smaller and rural hospitals. However, these deficiencies seem to reflect a lack of opportunity rather than a lack of interest. PMID- 17355297 TI - Macrosomic infants are not all equal. AB - AIMS: To see whether macrosomic infants have different morbidity according to maternal screening results for gestational diabetes mellitus (GDM) and ethnicity. METHODS: After excluding infants of women with diabetes, the National Women's Hospital database identified 134 infants who were delivered in 2003 and weighed >or= 4500 g. Case notes were reviewed to record risk factors for macrosomia, delivery details and neonatal morbidity. Outcomes were analysed according to screening results for GDM and compared between Polynesian and Asian women. RESULTS: Body mass index (BMI) was calculated in 29% of women, and GDM screening was undertaken in 51%. Infants of women who had a screening glucose < 7.2 mmol/L compared to >or= 7.8 mmol/L had lower rates of admission to the neonatal intensive care unit (NICU) (6.4 vs 28.6%, P=0.049), had less respiratory distress (3.2 vs 23.8%P=0.033) and display a trend to less require intravenous dextrose (6.4 vs 23.8%P=0.10). Maternal BMI was lower in Asian (26.5 +/- 4.4 kg/m(2)) compared to Polynesian women (35.2 +/- 8.1 kg/m(2), P=0.008). More Asian women had a Caesarean delivery (73.3 vs 25%P<0.001) and their infants were more likely to be admitted to NICU (33.3 vs 7.7%P=0.02), require intravenous dextrose (20 vs 1.9%P=0.03) and have respiratory distress (26.7 vs 3.8%P=0.02). CONCLUSION: Risk factors for macrosomia are not assessed adequately, which may contribute to morbidity. Using a birthweight >or= 4500 g to define macrosomia is associated with disparate morbidity between ethnicities that have different body compositions. PMID- 17355298 TI - A survey of clinician and patient attitudes towards the use of progesterone for women at risk of preterm birth. AB - BACKGROUND AND AIMS: To assess the current use of vaginal progesterone in women at increased risk of preterm birth among practitioners within Australia and New Zealand, and the willingness of both clinicians and women to participate in a randomised controlled trial to further evaluate the role of progesterone in preterm birth. METHODS: A survey of fellows and members of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, and women who had a spontaneous preterm birth at less than 34 weeks gestation, at the Women's and Children's Hospital was conducted. RESULTS: A total of 1430 surveys were distributed to members and fellows, of which 738 (52%) were returned. Of these, 490 were from currently practising obstetricians (34% of total college membership). Twelve of the 490 (2%) respondents indicated that they currently use progesterone in women with a previous spontaneous preterm birth at less than 34 weeks gestation. Of the respondents, 317 (65%) indicated a willingness to participate in a multicentred randomised controlled trial assessing the use of progesterone in women with a previous spontaneous preterm birth at less than 34 weeks gestation. A total of 207 eligible women identified from the hospital database were sent a questionnaire, with responses obtained from 119 women (57%). Overall, women were satisfied with their preterm birth experience. Fifty-two women (44%) indicated a willingness to consider participation in a randomised trial of vaginal progesterone. CONCLUSIONS: Progesterone is not widely used in Australia and New Zealand for women considered at increased risk of preterm birth. Conducting a randomised trial of vaginal progesterone is feasible. PMID- 17355299 TI - Maternal morbidity and mortality associated with elective Caesarean delivery at a university hospital in Nigeria. AB - BACKGROUND: Data about maternal outcomes of elective Caesarean section in low income countries are limited. AIMS: To estimate the maternal morbidity and mortality associated with elective Caesarean delivery at a Nigerian University hospital. METHODS: Retrospective analysis of all elective Caesarean deliveries at the Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria (1990-2005). For each case of elective Caesarean delivery, four parturients who achieved non operative vaginal delivery following spontaneous onset of labour were selected to serve as a referent group. Morbidity outcomes and mortality among women who had elective Caesarean delivery were compared with those of the referent group to estimate their comparative risks. Level of significance was put at P<0.05. RESULTS: A total of 164 elective Caesarean sections were performed out of 6882 deliveries (2.4%). All morbidities were more frequent among women who had elective Caesarean section compared to those who had vaginal delivery but only peripartum blood transfusion (11.6 vs 5.6%), puerperal febrile morbidity (11.0 vs 4.7%), unplanned readmission (4.3 vs 1.4%), mean fall in haemoglobin concentration (1.5 +/- 0.6 vs 0.5 +/- 0.7 g/dL) and mean hospital stay (13.3 +/- 8.8 vs 6.2 +/- 5.4 days) showed statistically significant differences. There was one maternal death among the elective Caesarean section group, giving a maternal mortality ratio of 6.1:1000 deliveries, which was not significantly different from 3.0:1000 deliveries in the referent group. CONCLUSION: Elective Caesarean delivery in this hospital is certainly accompanied by considerable maternal risks and should be offered to pregnant women with extreme caution. Efforts should be made to improve its safety by investigating and rectifying the factors responsible for the associated severe maternal complications. PMID- 17355300 TI - Calcium supplementation in pregnancy and its impact on blood pressure in children and women: follow up of a randomised controlled trial. AB - BACKGROUND: Follow up of participants in trials of antenatal calcium supplementation has reported an impact on blood pressure among mothers and children. AIMS: To determine whether blood pressure at 4-7 years follow up would be lower for calcium-supplemented mothers in the Australian Calcium Trial (ACT) and for their children. METHODS: This follow up targeted 414 of the original ACT participants with liveborn infants who lived in South Australia. Mothers and their children attended the Women's and Children's Hospital for anthropomorphic examination. Information on lifestyle factors was collected by questionnaire. Descriptive statistics examined differences between respondents and non respondents and multiple regression models examined associations with blood pressure. RESULTS: Blood pressure and body measurements were available on 45 and 43% of eligible women and children, respectively; questionnaire data were available on 50% of this cohort. At follow up, there were no differences between treatment groups in blood pressure in the women or their children. Both children of women who had high blood in pregnancy (pre-eclampsia or pregnancy-induced hypertension) and the women themselves had higher systolic and diastolic blood pressure at follow up. Among children, there was a trend towards an interaction with the treatment group with both systolic and diastolic blood pressure at follow up. CONCLUSION: There is no evidence that the impact of calcium supplementation in reducing the risk of high blood pressure in pregnancy is sustained 4-7 years after the index pregnancy either in woman or in their children; however, calcium supplementation may lower blood pressure in children of pregnant women with hypertension. PMID- 17355301 TI - Adequacy of prenatal care and neonatal mortality in infants born to mothers with and without antenatal high-risk conditions. AB - BACKGROUND: Previous studies have found that inadequate prenatal care was associated with increased neonatal mortality in the general pregnant women. AIMS: To examine the association between adequacy of prenatal care and neonatal mortality in the presence and absence of antenatal high-risk conditions. METHODS: We conducted a retrospective cohort study of infants based on 1995-2000 vital statistics data in the USA. The relative risk for neonatal death associated with adequacy of prenatal care was estimated by multivariate logistic regressions with adjustment of confounding factors. RESULTS: Inadequate prenatal care was associated with increased neonatal mortality when pregnancies were complicated by anaemia, cardiac disease, lung disease, chronic hypertension, diabetes, renal disease, pregnancy-induced hypertension, and previous preterm/small-for gestational-age birth. The observed association also existed in the absence of these antenatal high-risk conditions. Overutilisation of prenatal care was associated with increased risk of neonatal deaths in both the presence and the absence of antenatal high-risk conditions. When gestational age at delivery and birthweight were further adjusted, the observed association between inadequate prenatal care and neonatal mortality was not significant in pregnancies with various high-risk conditions. CONCLUSIONS: Inadequate prenatal care is associated with increased neonatal death in both the presence and the absence of antenatal high-risk conditions. The observed association between inadequate prenatal care and neonatal mortality may be mediated by increased risk of preterm delivery and low birthweight in these pregnancies. Overutilisation of prenatal care is associated with potential risks for fetal and neonatal development, leading to increased neonatal mortality. PMID- 17355302 TI - A customized birthweight centile calculator developed for an Australian population. AB - Customized percentiles improve the differentiation between constitutional and pathological smallness of the fetus and the neonate. We studied data from 12420 pregnancies in Sydney to develop Australian coefficients for customized fetal growth and birthweight centiles. Significant coefficients were derived for maternal height, weight, parity and ethnic origin as well as gestational age and the baby's gender. Standardised comparison with results from previous reports from England and New Zealand shows marked similarities in the predicted birthweight at term, confirming international applicability of the concept of adjusting for constitutional factors when calculating the growth potential of an individual fetus. PMID- 17355303 TI - The Vabra aspirator versus the Pipelle device for outpatient endometrial sampling. AB - OBJECTIVE: To compare the effectiveness of the Vabra aspirator and the Pipelle device as an outpatient endometrial assessment tool. METHOD: This was a randomised, prospective trial conducted for a period of one year. RESULTS: A total of 147 patients were recruited, of which 71 were in the Vabra group and 76 were in the Pipelle arm. The procedure success rate in the Pipelle group was significantly higher than the Vabra arm (98.7 vs 88.7%, P=0.02). Adequate tissue yield was also significantly more in the Pipelle arm (73.3 vs 52.4%, P=0.02). Cost-benefit analysis revealed a higher average cost per patient in the Vabra group compared to the Pipelle arm. CONCLUSION: This study proved that the Vabra aspirator was not as effective as the Pipelle device in obtaining endometrial tissue for histological diagnosis. Despite its higher price per unit, the Pipelle device was a more cost-effective tool for outpatient endometrial assessment. PMID- 17355304 TI - The simple outpatient management of Bartholin's abscess using the Word catheter: a preliminary study. AB - INTRODUCTION: Bartholin's cysts/abscess affects 2% of women. Conventional treatment is marsupialisation under general anaesthetic. We evaluated a conservative approach in a non-randomised prospective interventional study over 12 months. METHOD: Women with a Bartholin's abscess were counselled and those who opted for the Word catheter (WC) had it inserted under local anaesthetic (follow up at one week and four weeks, when catheter was removed). Women recorded pain scores and completed a qualitative questionnaire and had telephone follow up at six months. Outcome measures were abscess resolution and acceptability of treatment. RESULTS: Fifty-eight women attended with a Bartholin's abscess requiring drainage. Twenty-three of 58 (40%) elected for marsupialisation. Thirty five of 58 (60%) women had a WC inserted. Twenty-seven of 35 (77%) women retained their catheter for four weeks (three catheters fell out within 24 h of insertion, three catheters fell out within one week, one fell out after 11 days and there was one failed insertion). One woman had a recurrence six months after treatment. Abscess resolution occurred in 34 of 35 (97%). No woman reported significant discomfort at one week. Twenty-four of 27 women (89%) said that if they suffered a recurrence, they would have another WC inserted. Three of 27 (11%) women had intercourse within the second week of catheter insertion and reported that it was not uncomfortable. Fourteen women who had marsupialisation were traced and none had suffered a recurrence six months after treatment. CONCLUSIONS: The WC is a safe and effective treatment for a Bartholin's abscess. It may be considered as an alternative to marsupialisation. PMID- 17355305 TI - High-risk human papillomavirus DNA testing and high-grade cervical intraepithelial lesions. AB - OBJECTIVE: To explore the role of high-risk human papillomavirus (HPV) DNA testing in the improvement of the recognition of cervical cancer and precancerous lesions in women with abnormal cervical cytology. METHODS: A total of 2152 women with abnormal cervical cytology were submitted to both HPV DNA testing and biopsy guided by colposcopy and the results were correlated. RESULTS: Positive rate of high-risk HPV DNA in groups of atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells, cannot exclude high-grade (ASC H), low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions was 53.7, 53.2, 84.6 and 93.0%, respectively. In each group, the detection rate of grade 2,3 cervical intraepithelial neoplasia (CIN 2,3) or cervical cancer in patients with positive HPV DNA was significantly higher than that with negative HPV DNA (P<0.05). In ASC-US group, the negative predictive value of high-risk HPV DNA testing for detection of CIN 2,3 and cervical cancer was 99.8% and the sensitivity 98%. CONCLUSION: HPV DNA testing is a useful indicator in the management of patients with ASC-US and plays an important role in the evaluation of risk for CIN 2,3 and cervical cancer. PMID- 17355306 TI - The use of complementary medicine and therapies by patients attending a reproductive medicine unit in South Australia: a prospective survey. AB - BACKGROUND: There is limited research describing the use of complementary medicines (CM) and therapies among patients with infertility. OBJECTIVE: (i) To examine the use of CM by subjects attending an infertility clinic at their first consultation and six months later; (ii) to examine men's and women's views on the effectiveness and safety of these practices; and (iii) to examine the documentation of the use of CMs and therapies in clinical notes. DESIGN: A prospective survey of 100 consecutive new patients presenting to an infertility clinic. Subjects were requested to complete a self-administered questionnaire at their first visit and six months later. A retrospective audit of 200 patient records. RESULTS: A response rate of 72% was obtained. Sixty-six percent of patients attending the infertility clinic in South Australia used CMs. Six months following the initial consultation the use of CMs had declined. The most commonly used CMs included multivitamins, herbs, and mineral supplements, and subjects consulted most frequently with naturopaths, chiropractors and acupuncturists. The use of CMs and therapies was poorly documented by clinical staff. CONCLUSION: Complementary medicines and therapies are widely used by patients with infertility. Health-care practitioners and fertility specialists need to be proactive in acquiring and documenting the use of these practices. There is a need to provide further information to patients on the use of CMs and therapies. Further research examining the reasons for use of CMs and therapies is needed. PMID- 17355307 TI - 'Spontaneous/non-surgical pneumoperitoneum' in a 34-week-pregnant patient. PMID- 17355308 TI - Re: Obstetric-induced incontinence: a black hole of preventable morbidity. PMID- 17355309 TI - Re: Obstetric-induced incontinence: a black hole of preventable morbidity. PMID- 17355311 TI - Re: Case report of failed tubal occlusion using Essure pbc (permanent birth control) hysteroscopic sterilisation procedure. PMID- 17355313 TI - Re: Intrapartum analgesia and its association with post-partum back pain and headache in nulliparous women. PMID- 17355314 TI - Re: Radical trachelectomy. PMID- 17355315 TI - Thyrotrophin-releasing hormone decreases feeding and increases body temperature, activity and oxygen consumption in Siberian hamsters. AB - Thyrotrophin-releasing hormone (TRH) is known to play an important role in the control of food intake and energy metabolism in addition to its actions on the pituitary-thyroid axis. We have previously shown that central administration of TRH decreases food intake in Siberian hamsters. This species is being increasingly used as a physiological rodent model in which to understand hypothalamic control of long-term changes in energy balance because it accumulates fat reserves in long summer photoperiods, and decreases food intake and body weight when exposed to short winter photoperiods. The objectives of our study in Siberian hamsters were: (i) to investigate whether peripheral administration of TRH would mimic the effects of central administration of TRH on food intake and whether these effects would differ dependent upon the ambient photoperiod; (ii) to determine whether TRH would have an effect on energy expenditure; and (iii) to investigate the potential sites of action of TRH. Both peripheral (5-50 mg/kg body weight; i.p.) and central (0.5 microg/ml; i.c.v.) administration of TRH decreased food intake, and increased locomotor activity, body temperature and oxygen consumption in the Siberian hamster, with a rapid onset and short duration of action. Systemic treatment with TRH was equally effective in suppressing feeding regardless of ambient photoperiod. The acute effects of TRH are likely to be centrally mediated and independent of its role in the control of the production of thyroid hormones. We conclude that TRH functions to promote a catabolic energetic state by co-ordinating acute central and chronic peripheral (thyroid-mediated) function. PMID- 17355316 TI - The role of the vagus nerve in mediating the long-term anorectic effects of leptin. AB - Leptin, the product of the obese (ob) gene, is mainly known for its regulatory role of energy balance by direct activation of hypothalamic receptors. Recently, its function in the acute control of food intake was additionally attributed to activation of the vagus nerve to regulate meal termination. Whether vagal afferent neurones are involved in longer term effects of leptin on food intake, however, remains undetermined. Using vagotomised (VGX) rats, we sought to clarify the contributions of vagal afferents in mediating the long-lasting effect of leptin on appetite suppression. Intraperitoneal (i.p.) injection of leptin (3.5 mg/kg) attenuated food intake at 4, 6, 8 and 24 h and body weight at 24 h postinjection in SHAM-operated rats; however, this response was not abrogated by vagotomy. In a separate study using immunohistochemistry, we observed leptin induced Fos expression in the nucleus tractus solitarii, a brain structure where vagal afferent fibres terminate. This signal was not attenuated in VGX animals compared to the SHAM group. Moreover, leptin treatment led to a similar level of nuclear STAT3 translocation, a marker of leptin signalling, in the hypothalami of SHAM and VGX animals. In addition to the effects of leptin, vagotomy surgery itself resulted in a decrease of 24 h food intake. Analyses of brains from saline treated VGX animals revealed a significant induction of Fos in the nucleus tractus solitarii and changes in agouti-related peptide and pro-opiomelanocortin mRNA expression in the hypothalamus compared to their SHAM counterparts, indicating that the vagotomy surgery itself induced a modification of brain activity in areas involved in regulating appetite. Collectively, our data suggest that vagal afferents do not constitute a major route of mediating the regulatory effect of leptin on food intake over a period of several hours. PMID- 17355317 TI - Cellular distribution of the GABAA receptor-modulating 3alpha-hydroxy, 5alpha reduced pregnane steroids in the adult rat brain. AB - The 3alpha-hydroxy,5alpha-reduced pregnane steroids, allopregnanolone and allotetrahydrodeoxycorticosterone, are the most potent endogenous positive modulators of GABA(A) receptor-mediated inhibition. This study presents the first immunohistochemical examination of the cellular distribution of 3alpha hydroxy,5alpha-reduced pregnane steroids across the brain. We found a widespread distribution in the adult rat, with dense immunolabelling in the olfactory bulb, striatum and cerebral cortex, and lower density labelling in the brainstem reticular formation. In general terms, this distribution accords with the regional concentrations of 3alpha-hydroxy,5alpha-reduced steroids determined, in other laboratories, by brain region sampling and either gas chromatography-mass fragmentography or radioimmunoassay. However, immunohistochemistry allowed for a more detailed examination of regional distribution and cellular specificity. All immunoreactivity was confined to the cell bodies and thick dendrites of neurones; no identifiable glia were labelled. In most brain areas, the location and morphology of labelled cells identified them as excitatory neurones. In addition, cell populations known to be projecting GABAergic neurones (e.g. cerebellar Purkinje cells) were immunoreactive, whereas local inhibitory neurones generally were not. The cellular distribution of 3alpha-hydroxy,5alpha-reduced steroids suggests that sensory, motor, limbic and homeostatic systems can be influenced by neurosteroids at multiple stages of processing. PMID- 17355318 TI - Physiological studies of stress responses in the hypothalamus of vasopressin enhanced green fluorescent protein transgenic rat. AB - Arginine vasopressin (AVP) plays an important role in stress-induced activation of the hypothalamic-pituitary adrenal axis. In the present study, AVP-enhanced green fluorescent protein (eGFP) transgenic rats were used to investigate changes in AVP-eGFP expression in the hypothalamic paraventricular nucleus (PVN) and the median eminence (ME) upon exposure to stress conditions. The eGFP fluorescence in the parvocellular division of the PVN (pPVN) was markedly increased 5 days after bilateral adrenalectomy (ADX) and it was colocalised with corticotrophin releasing hormone-like immunoreactivity in the pPVN. Peripheral administration of dexamethasone completely suppressed the increase of eGFP fluorescence in the pPVN and the external layer of the ME (eME) after bilateral ADX. Significant increases of eGFP fluorescence were observed in the pPVN 6, 12, 24 and 48 h after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS). In the eME, eGFP fluorescence was significantly increased 48 h after i.p. administration of LPS. By contrast, eGFP fluorescence changed neither in the magnocellular division of the PVN, nor the internal layer of the ME after i.p. administration of LPS. Our results indicate that AVP-eGFP transgenic rats are useful animal model to study dynamic changes of AVP expression in the hypothalamus under stressful conditions. PMID- 17355319 TI - Effects of adrenalectomy on the excitability of neurosecretory parvocellular neurones in the hypothalamic paraventricular nucleus. AB - Glucocorticoids are well known to inhibit the release of hypophysiotrophic hormones from neurones originating in the paraventricular nucleus (PVN), but the cellular mechanisms of the inhibition are not well understood. Here, we examined the effects of adrenalectomy (ADX) on the spontaneous firing activity in the neurosecretory parvocellular PVN neurones of rat brain slices. The neurones were identified by injecting a retrograde dye into the pituitary stalk and classified according to their electrophysiological properties. The intranuclear distribution, electrophysiological properties, and hypophysiotrophic hormone phenotype of the labelled type II PVN neurones were similar to neurosecretory parvocellular PVN neurones. In the neurones of sham-operated rats under the cell attached recording mode, we observed three spontaneous activity patterns: tonic regular (24%), tonic irregular (36%), and silent (40%). Noradrenaline (100 microM) induced an excitatory or an inhibitory effect on the spontaneous activity. Noradrenergic excitation was blocked by prazosin (2 microM, alpha(1) adrenoceptor antagonist), and mimicked by phenylephrine (100 microM, alpha(1) adrenoceptor agonist), whereas noradrenergic inhibition was blocked by yohimbine (2 microM, alpha(2)-adrenoceptor antagonist) and mimicked by clonidine (50 microM, alpha(2)-adrenoceptor agonist). In the neurones of ADX rats, we found burst firing in 35% of neurones tested and an increase in the frequency of spontaneous firing. The burst firing was not observed in the neurones of the sham operated rats. ADX caused a 1.7-fold increase in the proportion of neurones showing the noradrenergic excitation. Supplementation of the ADX rats with corticosterone (10 mg pellet) reversed the ADX-induced burst firing, and the potentiation of noradrenergic excitation. In summary, our results show that removal of corticosterone by ADX can elevate the neuronal excitability by increasing the spontaneous firing rate and by potentiating the alpha(1) adrenoceptor-mediated noradrenergic excitation, and it can facilitate hormone release by inducing burst firing. Our results provide new insight to the cellular mechanisms of the feedback inhibition by glucocorticoids in the neurosecretory parvocellular neurones of the PVN. PMID- 17355320 TI - Sex differences in the chloride cotransporters, NKCC1 and KCC2, in the developing hypothalamus. AB - In immature neurones, high basal [Cl(-)](i) results in membrane depolarisation following GABA(A) receptor activation, which is critical for various developmental processes including steroid-mediated sexual differentiation of the hypothalamus. Previously, we demonstrated that oestradiol enhances GABA-mediated Ca(2+) influx in neonate hypothalamus and that Ca(2+) induced activation of the transcription factor, cyclicAMP response element binding protein (CREB), was higher in male (high oestradiol) relative to female neonate hypothalamus. Based on these results, we hypothesised that expression of developmentally regulated chloride cotransporters may be sexually dimorphic. Here, we investigate the expression of the chloride cotransporters, NKCC1 (Na-K-2Cl(-)) and KCC2 (K-Cl(-)) in neonate mediobasal hypothalamus of male and female rats. The NKCC1 transporter moves Cl(-) into cells and helps maintain depolarising GABA action while the KCC2 transporter has the opposite effect by moving Cl(-) out of cells. NKCC1 mRNA levels were higher in males than females on the day of birth (postnatal day 0; PND 0) and total NKCC1 protein levels were significantly higher in males than females on embryonic day (ED) 20 and PND0. Levels of activated phosphorylated NKCC1 (pNKCC1) were not sexually dimorphic. Females were treated with a masculinising dose of oestradiol benzoate (EB; 100 microg; EB-females) on PND0. Total NKCC1 protein levels in tissue processed on PND1 and PND2 were similar in EB-females and oil-treated PND0 males and females. However, pNKCC1 protein levels measured on PND2 (but not PND1) were significantly higher in EB-treated females relative to oil-treated males and females. By contrast, KCC2 mRNA levels were significantly lower in males relative to females on PND0. KCC2 protein was not detectable on ED20 or PND0 but was significantly lower in males relative to females on PND5. These results suggest a complex relationship between KCC2 and NKCC1 mRNA and protein in developing brain that is not easily linked to regulation by oestradiol. PMID- 17355321 TI - Inhibition of vasopressin V1b receptor translation by upstream open reading frames in the 5'-untranslated region. AB - The 5'-UTR of the vasopressin V1b receptor (V1bR) mRNA contains small open reading frames (ORF) located upstream (u) of the main ORF encoding the V1bR. The ability of the three proximal uORFs to be translated into peptides and their influence on V1bR translation was examined using fusion constructs of uORFs and V5 epitope, or ATG/ATA uORF mutations in the V1bR cDNA. In vitro translation and western blot analysis after transfection of uORF1-V5 or uORF2-V5 into cells revealed that uORF1 can be translated. As predicted by computer analysis, in vitro translation using a rabbit reticulocyte/canine microsome system, immunohistochemistry and western blot in membranes of transfected cells with uORF1-V5 revealed translocation of the uORF1 peptide into membrane fractions. In vitro translation of V1bR cDNA with mutations of the two uORFs proximal to the initiating methionine, uORFs 1 and 2 (Mut 1-2), or uORF2 (Mut 2) showed significantly increased translation of a 46 kDa band corresponding to the V1bR, compared with wild-type (WT) V1bR, an effect that was attenuated by cotranslation of uORF1-V5. Consistently, VP-induced inositol phosphate formation was higher in Chinese hamster ovay cells transfected with Mut 1-2 than with WT V1bR. Immunohistochemical and western blot analysis, using an antibody against uORF1, revealed peptide immunoreactivity in rat pituitary but not in liver. Pituitary uORF immunoreactivity increased following glucocorticoid administration. The present study shows that uORFs in the 5'-UTR of the V1bR mRNA inhibit V1bR translation, and suggests that translation of a 38-amino acid membrane peptide encoded by uORF1 exerts tonic inhibition of V1bR translation. PMID- 17355322 TI - Prevention of hamstring strains in elite soccer: an intervention study. AB - The purpose was to test the effect of eccentric strength training and flexibility training on the incidence of hamstring strains in soccer. Hamstring strains and player exposure were registered prospectively during four consecutive soccer seasons (1999-2002) for 17-30 elite soccer teams from Iceland and Norway. The first two seasons were used as baseline, while intervention programs consisting of warm-up stretching, flexibility and/or eccentric strength training were introduced during the 2001 and 2002 seasons. During the intervention seasons, 48% of the teams selected to use the intervention programs. There was no difference in the incidence of hamstring strains between teams that used the flexibility training program and those who did not [relative risk (RR)=1.53, P=0.22], nor was there a difference compared with the baseline data (RR=0.89, P=0.75). The incidence of hamstring strains was lower in teams who used the eccentric training program compared with teams that did not use the program (RR=0.43, P=0.01), as well as compared with baseline data for the same intervention teams (RR=0.42, P=0.009). Eccentric strength training with Nordic hamstring lowers combined with warm-up stretching appears to reduce the risk of hamstring strains, while no effect was detected from flexibility training alone. These results should be verified in randomized clinical trials. PMID- 17355323 TI - Profile of physical activity behaviors among Swedish women aged 56-75 years. AB - The aim of this study was to assess profiles of physical activity (PA) behavior using accelerometers among middle-aged and elderly women in free-living conditions. A subset of 133 women aged 56-75 years from the population-based Swedish Mammography Cohort with valid accelerometer data was included in the analysis. The proportion of women who met the PA recommendation of accumulating 30 min of moderate-to-vigorous physical activity (MVPA), in either one continuous bout or several shorter bouts lasting 8-10 min, on five or more days/week was 31%. The precision of mean daily estimates of MVPA and of inactivity based on 7 days monitoring was 0.80 and 0.86, respectively. On average, participants spent 103 min/day on MVPA, but only about a third of that time was accumulated in the recommended pattern of bouts lasting at least 8-10 min. Obese women had, on average, one bout of MVPA less than normal-weight women (mean 3.6 bouts/day). The mean MVPA decreased 10 min/day with every 5-year increase in age. A low proportion of women accumulated MVPA in the pattern recommended for health benefits. The proportion would increase considerably if women maintained their current amount of MVPA but increased the duration of each bout of MVPA. PMID- 17355324 TI - Low-intensity training dissociates metabolic from aerobic fitness. AB - This study investigated the effect of prolonged whole-body low-intensity exercise on blood lipids, skeletal muscle adaptations and aerobic fitness. Seven male subjects completed a 32-day crossing of the Greenland icecap on cross-country skies and before and after this arm or leg cranking was performed on two separate days and biopsies were obtained from arm and leg muscle, and venous blood was sampled. During the crossing, subjects skied for 342+/-42 min/day and body mass was decreased by 7.1+/-0.7 kg. Peak leg oxygen uptake (4.6+/-0.2 L/min) was decreased (P<0.05) by 7% whereas peak arm oxygen uptake (3.0+/-0.2 L/min) remained unchanged. Total and low-density lipoprotein cholesterol (5.0+/-0.2 and 3.20.2 mmol/L) were decreased by 8% and 20%, respectively. Muscle beta-hydroxy acyl-CoA dehydrogenase activity was increased with 22% in arm (P=0.08) and remained unchanged in leg muscle. Hormone sensitive lipase activity was similar in arm and leg muscle prior to the expedition and was not significantly affected by the crossing. In conclusion, an improved blood lipid profile and thus metabolic fitness was present after prolonged low-intensity training and this occurred in spite of a decreased aerobic fitness and an unchanged arm and leg muscle hormone-sensitive lipase activity. PMID- 17355326 TI - Exploring disparities between global HIV/AIDS funding and recent tsunami relief efforts: an ethical analysis. AB - OBJECTIVE: To contrast relief efforts for the 26 December 2004 tsunami with current global HIV/AIDS relief efforts and analyse possible reasons for the disparity. METHODS: Literature review and ethical analysis. RESULTS: Just over 273,000 people died in the tsunami, resulting in relief efforts of more than US$10 bn, which is sufficient to achieve the United Nation's long-term recovery plan for South East Asia. In contrast, 14 times more people died from HIV/AIDS in 2004, with UNAIDS predicting a US$8 bn funding gap for HIV/AIDS in developing nations between now and 2007. This disparity raises two important ethical questions. First, what is it that motivates a more empathic response to the victims of the tsunami than to those affected by HIV/AIDS? Second, is there a morally relevant difference between the two tragedies that justifies the difference in the international response? The principle of justice requires that two cases similarly situated be treated similarly. For the difference in the international response to the tsunami and HIV/AIDS to be justified, the tragedies have to be shown to be dissimilar in some relevant respect. Are the tragedies of the tsunami disaster and the HIV/AIDS pandemic sufficiently different, in relevant respects, to justify the difference in scope of the response by the international community? CONCLUSION: We detected no morally relevant distinction between the tsunami and the HIV/AIDS pandemic that justifies the disparity. Therefore, we must conclude that the international response to HIV/AIDS violates the fundamental principles of justice and fairness. PMID- 17355327 TI - Population aging and international development: addressing competing claims of distributive justice. AB - To date, bioethics and health policy scholarship has given little consideration to questions of aging and intergenerational justice in the developing world. Demographic changes are precipitating rapid population aging in developing nations, however, and ethical issues regarding older people's claim to scarce healthcare resources must be addressed. This paper posits that the traditional arguments about generational justice and age-based rationing of healthcare resources, which were developed primarily in more industrialized nations, fail to adequately address the unique challenges facing older persons in developing nations. Existing philosophical approaches to age-based resource allocation underemphasize the importance of older persons for developing countries and fail to adequately consider the rights and interests of older persons in these settings. Ultimately, the paper concludes that the most appropriate framework for thinking about generational justice in developing nations is a rights-based approach that allows for the interests of all age groups, including the oldest, to be considered in the determination of health resource allocation. PMID- 17355328 TI - The perspectives of researchers on obtaining informed consent in developing countries. AB - BACKGROUND: The doctrine of informed consent (IC) exists to protect individuals from exploitation or harm. This study into IC was carried out to investigate how different researchers perceived the process whereby researchers obtained consent. It also examined researchers' perspectives on what constituted IC, and how different settings influenced the process. METHODS: The study recorded in-depth interviews with 12 lecturers and five doctoral students, who had carried out research in developing countries, at a leading school of public health in the United Kingdom. A purposive, snowballing approach was used to identify interviewees. RESULTS: Although the concept and application of the doctrine of IC should have been the same, irrespective of where the research was carried out, the process of obtaining it had to be different. The setting had to be taken into consideration and the autonomy of the subject had to be respected at all times. In areas of high illiteracy, and where understanding of the subject was likely to be a problem, there was an added responsibility placed on the researcher to devise innovative ways of carrying out the study, taking into consideration the peculiarities of the environment. CONCLUSION: The ethical issues for IC were the same, irrespective of where the research was conducted. However, because the backgrounds, setting, and knowledge of populations differed, there was the need to be similarly sensitive in obtaining consent. The problems of obtaining genuine IC were not limited to developing countries. PMID- 17355329 TI - Ethical and regulatory issues surrounding African traditional medicine in the context of HIV/AIDS. AB - It has been estimated that more than 80% of people in Africa use traditional medicine (TM). With the HIV/AIDS epidemic claiming many lives in Africa, the majority of people affected rely on TM mainly because it is relatively affordable and available to the poor populations who cannot afford orthodox medicine. Whereas orthodox medicine is practiced under stringent regulations and ethical guidelines emanating from The Nuremburg Code, African TM seems to be exempt from such scrutiny. Although recently there have been calls for TM to be incorporated into the health care system, less emphasis has been placed on ethical and regulatory issues. In this paper, an overview of the use of African TM in general, and for HIV/AIDS in particular, is given, followed by a look at: (i) the relative laxity in the application of ethical standards and regulatory requirements with regards to TM; (ii) the importance of research on TM in order to improve and demystify its therapeutic qualities; (iii) the need to tailor-make intellectual property laws to protect traditional knowledge and biodiversity. A framework of partnerships involving traditional healers' associations, scientists, policy makers, patients, community leaders, members of the communities, and funding organizations is suggested as a possible method to tackle these issues. It is hoped that this paper will stimulate objective and constructive debate that could enhance the protection of patients' welfare. PMID- 17355330 TI - Ethical considerations in African traditional medicine: a response to Nyika. AB - Like other so-called 'parallel' practices in medicine, traditional medicine (TM) does not avoid criticism or even rejection. Nyika's article 'Ethical and Regulatory Issues Surrounding African Traditional Medicine in the Context of HIV/AIDS' looks at some of the issues from a traditional Western ethical perspective and suggests that it should be rejected. I respond to this article agreeing with Nyika's three major criticisms: lack of informed consent, confidentiality and paternalism. However, as traditional healers are consulted by over 70% of South Africans before any other type of healthcare professional, a blanket negation of TM is not possible, nor is it politically feasible. A pragmatic approach would be to work within the current structures for positive change. I point out that, as all cultural practices do, TM will change over time. Yet, until some regulations and change occur, the problem of harm to patients remains a major concern. PMID- 17355331 TI - How not to compare Western scientific medicine with African traditional medicine. AB - In his commentary on Aceme Nyika's paper 'Ethical and Regulatory Issues Surrounding African Traditional Medicine in the Context of HIV/AIDS', Godfrey B. Tangwa charges the author with inappropriately using expressions, terminology and criteria of evaluation appropriate in Western scientific medicine to judge African traditional medicine (TM). He seriously frowns on Nyika's suggestion that African TM needs to be incorporated into, and subjected to the canons of Western scientific medicine. Such a suggestion, he believes, is a prescription for invasion, colonization and exploitation so characteristic of the relationship between Africa and the Western world. However, he thinks that African TM is quite compatible with Western scientific medicine. PMID- 17355332 TI - Is a national standard of care always the right one? PMID- 17355334 TI - Do the ravages of the HIV/AIDS epidemic ethically justify mandatory HIV testing? PMID- 17355335 TI - Disparity in medical fees for donor and self freeze-thaw embryo transfer cycle--a covert form of embryo commercialization? PMID- 17355337 TI - Effect of betaine on growth hormone pulsatile secretion and serum metabolites in finishing pigs. AB - An experiment was conducted to investigate the effect of dietary betaine (0%, 0.125%) on growth performance, growth hormone (GH) pulsatile secretion and serum metabolites in crossbred finishing pigs. Three replications of eight pigs (four barrows and four gilts) were used for each treatment, and blood samples for the determination of GH pulsatile secretion were collected every 15 min for 3 h. The results showed that betaine supplementation resulted in 5.45% (p<0.05) increase in average daily gain, whereas average daily feed intake and feed to gain ratio were not affected. Serum basal GH level, mean GH level and GH pulse amplitude were elevated by 41.79% (p<0.01), 48.98% (p<0.01) and 35.05% (p<0.05), respectively, with betaine treatment, but GH pulse frequency and pulse duration remained unchanged (p>0.05). Serum urea nitrogen concentration in pigs fed betaine was 21.58% lower than that of controls (p<0.01), whereas total protein level was significantly increased with betaine supplementation (p<0.05). The study suggests that betaine could promote growth by enhancing GH secretion in finishing pigs. PMID- 17355338 TI - In vivo metabolic effects of naringenin in the ethanol consuming rat and the effect of naringenin on adipocytes in vitro. AB - Naringenin is a bioactive flavanone involved in the inhibition of drug metabolism which exhibits antioxidant, anti-inflammatory and anticancerogenic properties and which recently appeared to be a factor mitigating the hyperlipidaemic effects in rats and rabbits. In the performed experiment, the effect of naringenin, administered intragastrically (50 mg/kg) for 2 weeks to normal and ethanol drinking rats, on insulin and leptin levels and on some metabolic parameters was investigated. Naringenin did not change the hormone levels in any group of rats. Blood glucose, triglyceride, total, esterified and free cholesterol and high density lipoprotein-cholesterol concentrations were also unaffected by this compound. Only free fatty acids were elevated after the naringenin treatment in the water-drinking rats. In spite of unchanged glucose and insulin concentrations in blood, the tested flavanone reduced the glucose/insulin ratio in ethanol receiving rats. Liver triglycerides, elevated due to ethanol ingestion, were partially normalized by naringenin. Other tested parameters like liver glycogen and cholesterol, muscle triglycerides and glycogen were not altered in any group of rats. The influence of naringenin (62.5, 125, 250 and 500 microM) on basal and insulin-stimulated glucose conversion to lipids (lipogenesis) as well as on basal and epinephrine-stimulated glycerol release (lipolysis) in the isolated rat adipocytes was also tested. The basal and the stimulated lipogenesis tended to be decreased in the presence of the flavanone (250 microM). This inhibitory effect intensified and was statistically significant at the highest concentration of naringenin. The tested compound did not evoke any effect on basal lipolysis while the epinephrine-stimulated process was limited at the highest concentration of the flavanone. Naringenin (62.5, 125, 250 and 500 microM) had no effect on leptin secretion from the isolated rat adipocytes. Results obtained in our studies demonstrate that naringenin exerts a very weak influence on carbohydrate and lipid metabolism of normal and ethanol-consuming rats and on metabolism of isolated rat adipocytes. PMID- 17355339 TI - Concentration of copper, iron, manganese and zinc in muscle, fat and bone tissue of lambs of the breed German Merino Landsheep in the course of the growing period and different feeding intensities. AB - A growth experiment with 108 lambs (breed German Merino Landsheep) was carried out in order to examine how gender, body weight and feeding intensity affect trace element concentrations in tissues and carcass. The lambs (50% male and 50% female) were fattened at three levels of feeding intensity ('low', 'medium' and 'high' by varying daily amounts of concentrate and hay) and slaughtered at different final body weights (30, 45 or 55 kg). Six male and six female animals were sacrificed at 18 kg live weight at the beginning of the comparative slaughter experiment. The left half carcass of each animal was divided into muscle tissue, fat tissue as well as bones and sinews and analysed for the trace elements copper (Cu), iron (Fe), manganese (Mn) as well as zinc (Zn). The body weight level influenced the Zn concentrations significantly in all tissues. In addition, the Fe concentration in the fat tissue was influenced by the body weight as well as the Cu content in the bone tissue. An influence due to gender could be seen for the Zn concentration in the muscle and fat tissue and for the Fe content in the fat and bone tissue as well as for the Cu concentration in the bones. The feeding intensity affected the Cu content in the muscle and bone tissue and also the Zn content in the muscle tissue. In the present study with lambs at body weight range from 18 to 55 kg on an average, 127 mg Fe, 87 mg Zn, 1.5 mg Cu as well as 1.1 mg Mn per kilogram dry matter were found in the bone tissue. In lamb muscle tissue combined from all parts (body weight range from 18 to 45 kg, both genders) the highest concentrations were for Zn and Fe [3.42 and 1.31 mg/100 g meat (wet weight basis)], while Cu remained far below these levels (0.08 mg/100 g meat and Mn was even below the detection limit of 0.025 mg/kg). Lamb muscle is a valuable source for highly available haem-Fe as well as for Zn and Cu in human nutrition. PMID- 17355340 TI - Effect of lactoferrin on selected immune system parameters and the gastrointestinal morphology in growing calves. AB - Lactoferrin (LF) is a cationic iron-binding glycoprotein that is abundantly expressed and secreted from glandular epithelial cells and a prominent component of the secondary granules of polymorphonuclear neutrophils. Various in vitro and in vivo experiments demonstrate anti-microbial, -viral, -mycotic and inflammatory effects of LF, associated with modulations of the immune system. Effects of oral administered LF on selected immune system parameters were studied in calves. Five calves were fed LF beginning on day 3 of life with colostral milk and starting on day 6 of life milk replacer enriched with 0.16% LF was fed. The average daily intake of LF per calf was 1.5-1.6 g/day. Additional five calves served as control group with identical treatment except for the LF supplementation. At the end of the study (day 61 of life), all calves were slaughtered and various tissues were sampled for histological and gene-expression studies. LF given orally was shown to act as an immunomodulatory agent by enhancing the size of Peyer's patches in the ileum and increasing blood serum immunoglobulin G levels. In addition, the number of peripheral blood leucocytes increased and mRNA levels of various interleukins (IL) such as IL-1beta, IL-8, IL 10 and interferon gamma (IFNgamma) in those cells in response to LF treatment were enhanced. In blood, the mRNA expression of the pro-inflammatory marker genes IL-1beta and IFNgamma decreased over 10-week treatment. Additionally, LF feeding decreased villus sizes in the jejunum. Together these findings emphasize the ability of LF to stimulate prominent immune system parameters and that it has the capacity to modulate the immune responses in a positive way. PMID- 17355341 TI - Influence of different calcium contents in diets supplemented with anionic salts on bone metabolism in periparturient dairy cows. AB - At the initiation of lactation, Ca homeostatic mechanisms have to react to a tremendous increase in demand for Ca. Mobilization of Ca from bone and increased absorption from the gastrointestinal tract are required to re-establish homeostasis. It has been shown that dietary anions play an important role in the prevention of milk fever by mobilizing Ca from bone and by increasing Ca absorption in the GI tract. The purpose of the present study was to investigate the influence of different Ca contents in diets supplemented with anionic salts on bone metabolism of dairy cows. Twenty-four holstein cows (housed inside, second to fourth lactation) without a milk fever history were divided into four groups (A, B, C, D). Each group was fed a different diet which was given from day 263 of gestation till the day of parturition. Group A and B received a low calcium diet (4 g/kg DM) whereas group C and D received a high Ca diet (8 g/kg DM). In addition group B and D received anionic salts. The DCAD was calculated with the formula: DCAD (mEq/kg DM)=(0.2 Ca2++0.16 Mg2++Na++K+)-(Cl-+0.6 S2-+0.65 P3-). Blood and urine samples were collected on days 256, 270 and 277 of gestation, on the day of parturition as well as the following 5 days and on days 9, 14 and 19 after parturition. Serum Ca, P, Mg, ICTP, OC, VITD, PTH and urinary pH were analysed. The bone resorption marker ICTP showed a significant increase after parturition in all the groups. On the contrary, the bone formation marker OC decreased after parturition in all the groups. The VITD concentrations in group D and the urinary pH in group B were significantly lower compared to the other groups (p<0.05). The Ca concentrations tended to be higher in group B around parturition than in all the other groups. No significant influence of the four different diets on all the other parameters could be shown. In conclusion, this data showed that the addition of anions and the different Ca contents had no significant influence on bone resorption and bone formation markers. This may be because of the fact that the dietary cation-anion balance was not low enough (DCAD-group A: 181 mEq/kg DM, group B: -48 mEq/kg DM, group C: 210 mEq/kg DM and group D: 28 mEq/kg DM) to induce a metabolic acidosis with all its positive effects on calcium metabolism. PMID- 17355342 TI - Food intake and ingredient profile affect viscosity of ileal digesta of dogs. AB - Two experiments were conducted to determine dietary factors affecting digesta viscosity. In experiment 1, six ileal-cannulated dogs were either full (607.1 kJ/BW0.67) or restricted (303.5 kJ/BW0.67) fed. In experiment 2, four dog foods were surveyed for effects on digesta viscosity based on protein source [animal protein (AP) or plant protein (PP)] or dietary fibre source [soluble dietary fibre (SDF) or insoluble dietary fibre (IDF)]. Dry matter (DM) intake was higher (p<0.05) when dogs were full (11.4 g/kg) compared with restricted fed (5.98 g/kg). Ileal digesta viscosity tended to be higher (p=0.07) for full fed [10,251 centipoise (cP)] compared with restricted-fed dogs (6677 cP). Ileal digesta viscosities were 6561, 11,074, 13,830 and 15,967 cP for dogs consuming IDF, SDF, AP and PP treatments respectively. Ileal DM concentrations were 11.4%, 13.6%, 14.8% and 14.8% for SDF, IDF, AP and PP treatments respectively. DM digestibility coefficients were lowest (71.2%) for the PP treatment and highest (88.7%) for the IDF treatment. Organic matter digestibilities followed a similar pattern. Ileal digesta viscosity of dogs appears to increase with increased diet intake, and increased ileal DM concentration. More digestible diets result in less ileal DM and lower viscosity constants. PMID- 17355343 TI - Diet type affects viscosity of ileal digesta of dogs and simulated gastric and small intestinal digesta. AB - Two experiments were conducted to determine effects of diet type on viscosity of ileal digesta of dogs and simulated gastric and small intestinal digesta. In experiment 1, three canned and three dry dog foods were surveyed for effects on ileal digesta viscosity. Experiment 2 evaluated the same six diets for effects on simulated gastric and small intestinal digesta. Canned diets and dry diets contained an average 22.7% and 89.9% dry matter (DM) respectively. Concentrations of total dietary fibre (TDF) in the diets ranged from 1.8% to 26.5%. Ileal digesta viscosities ranged from 1326 to 46,641 and 7748 to 10,208 cP for canned and dry treatments respectively. Ileal DM concentrations ranged from 8.2% to 16.2% and 15.4% to 15.8% for canned and dry treatments respectively. Dry matter intake ranged from 224 to 290 and 295 to 325 g/day for canned and dry treatments respectively. During gastric digestion simulation, viscosity peaked at 2 and 4 h for all three canned diets and dry diets respectively. During small intestinal digestion simulation, viscosity peaked between 6 and 12 h for most diets except one canned diet and one dry diet, which contained high concentrations of TDF (25.1% and 26.5% respectively). Viscosity of these solutions peaked between 12 and 18 h. Viscosity of ileal digesta and simulated gastric and small intestinal digesta was the lowest after consumption of canned diets with the exception of the canned diet containing very high concentrations of dietary fibre (25.1% TDF). Ileal digesta viscosity of dogs appears to be responsive to the diet type characteristics. PMID- 17355344 TI - Allometric scaling, metabolic body size and interspecies comparisons of basal nutritional requirements. AB - The amounts of specific substances needed per day that are generally thought to be nutritionally essential or conditionally important are similar among animal species when expressed per unit of energy consumed or per metabolic body size. Accordingly, a case is made that in addition to basal daily energy utilization, allometric scaling based on metabolic body size (3/4 power of mass or weight in kg) may be used to predict and compare basal nutrient requirements among widely varied species, as well as make comparative toxicological and other biological assessments and predictions. Furthermore, given the increasing evidence for allometric scaling for a broad range of biological phenomena (both empirical and theoretical) there is usually a good biological question to be answered when an organismal process deviates markedly from an allometric scale. PMID- 17355354 TI - Adjunctive local antibiotic therapy in the treatment of peri-implantitis II: clinical and radiographic outcomes. AB - AIM: To monitor over 12 months clinical and radiographic changes occurring after adjunctive local delivery of minocycline microspheres for the treatment of peri implantitis. MATERIAL AND METHODS: In 25 partially edentulous subjects, 31 implants diagnosed with peri-implantitis were treated. Three weeks after oral hygiene instruction, mechanical debridement and local antiseptic cleansing using 0.2% chlorhexidine gel, baseline (Day 0) parameters were recorded. Minocycline microspheres (Arestin) were locally delivered to each implant site with bone loss and a probing pocket depth (PPD) >or=5 mm. Rescue therapy with Arestin was allowed at Days 180 and 270 at any site exhibiting an increase in PPD>or=2 mm from the previous visit. The following clinical parameters were recorded at four sites/implant at Day 0, 10, 30, 60, 90, 180, 270 and 360: PPD, clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PlI). RESULTS: Six implants in six subjects were either rescued or exited because of persisting active peri-implantitis. Successful implants showed a statistically significant reduction in both PPD and percentage of sites with BOP between baseline and Day 360 (P<0.05). At mesial implant sites, the mean PPD reduction amounted to 1.6 mm (95% CI: 0.9-2.2 mm, P<0.001) and was accompanied by a statistically significant reduction of the BOP value (P<0.001). Binary regression analysis showed that the clinical parameters and smoking history could not discriminate between successfully treated and rescued or exited implants at any observation time point. CONCLUSION: Non-surgical mechanical treatment of peri implantitis lesions with adjunctive local delivery of microencapsulated minocycline led to positive effects on clinical parameters up to 12 months. PMID- 17355355 TI - Implant-retained oral appliances: a novel treatment for edentulous patients with obstructive sleep apnea-hypopnea syndrome. AB - OBJECTIVES: Mandibular repositioning appliances (MRAs) are a viable treatment alternative in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Because these appliances require retention in the patient's dentition, edentelous patients generally do not qualify for this treatment. This study describes our experiences with an implant-retained MRA in the treatment of edentulous OSAHS patients. PATIENTS AND METHODS: Six edentulous OSAHS patients were included in this study. Standard treatment consisted of the placement of four endosseous dental implants in the mandible and the construction of a new maxillary denture and a mandibular overdenture. Subsequently, an MRA was made. After a habituation and adjustment period, the effect of treatment was evaluated with polysomnography. Treatment was considered effective in cases where it yielded an apnea-hypopnea index <5. RESULTS: Of the six patients included, two did not tolerate the MRA because of pressure-induced discomfort on the labial mucosa in the maxilla. These two patients were offered an implant-retained overdenture and MRA in the maxilla. One of the two patients proceeded with this secondary treatment. Of the five patients completing the follow-up polysomnography, effective OSAHS treatment was attained in four. CONCLUSIONS: The results from this study suggest that an implant-retained MRA in the mandible is a viable treatment modality in edentulous OSAHS patients. Because the therapeutic effectiveness of this treatment may be compromised by excessive pressure of the MRA on the labial mucosa in the maxilla, we suggest that an implant-retained MRA in the maxilla be offered as a secondary treatment in selected patients. PMID- 17355356 TI - Evaluation of sinus floor elevation using a composite bone graft mixture. AB - BACKGROUND: The performance of implant surgery in the posterior maxilla often poses a challenge due to insufficient available bone. Sinus floor elevation was developed to increase needed vertical height to overcome this problem. The present study described and reported a simple, safe and predictable bone graft mixture for the sinus lifting procedure. MATERIAL AND METHODS: Seventy patients were recruited for this study and underwent a sinus lift procedure. All sites were treated with a composite graft of cortical autogenous bone, bovine bone and platelet-rich plasma (PRP). A total of 263 implants (171 Astra Tech and 92 Microdent) were placed either simultaneously or delayed. All sites were clinically and radiographically evaluated 24 months after their prosthetic loading. Biopsy samples were taken from 16 delayed implant placement sites at the time of their implant placement. RESULTS: A 100% implant success rate was found after 24 months of functioning. Only two Microdent implants failed before loading, which translates to a 99% overall implant success rate. No statistically significant differences were found between simultaneous and delayed implant placement. Image processing revealed 34+/-6.34% vital bone, 49.6+/-6.04% connective tissue and 16.4+/-3.23% remaining Bio-Oss particles. However, the histomorphometric analysis showed that the bovine bone was incorporated into new bone formation. CONCLUSION: The results showed that a composite graft comprised of cortical autogenous bone, bovine bone and PRP mixture can be successfully used for sinus augmentation. PMID- 17355357 TI - Resonance frequency analysis in relation to jawbone characteristics and during early healing of implant installation. AB - OBJECTIVES: To monitor resonance frequency analysis (RFA) in relation to the jawbone characteristics and during the early phases of healing and incorporation of Straumann dental implants with an SLA surface. MATERIAL AND METHODS: 17 Straumann 4.1 mm implants (10 mm) and 7 Straumann 4.8 mm implants (10 mm) were installed and ISQ determined at baseline and after 1, 2, 3, 4, 5, 6, 8 and 12 weeks. Central bone cores were analyzed from the 4.1 mm implants using micro CT for bone volume density (BVD) and bone trabecular connectivity (BTC). RESULTS: Pocket probing depths ranged from 2-4 mm and bleeding on probing from 5-20%. At baseline, BVD varied between 24% and 65% and BTC between 4.9 and 25.4 for the 4.1 mm implants. Baseline ISQ varied between 55 and 74 with a mean of 61.4. No significant correlations were found between BVD or BTC and ISQ Values. For the 4.8 mm diameter implants baseline ISQ values ranged from 57-70 with a mean of 63.3. Over the healing period ISQ values increased at 1 week and decreased after 2-3 weeks. After 4 weeks ISQ values, again increased slightly, no significant differences were noted over time. One implant (4.1 mm) lost stability at 3 weeks. Its ISQ value had dropped from 68 to 45. However the latter value was determined after the clinical diagnosis of instability. CONCLUSION: ISQ values of 57-70 represented homeostasis and implant stability. However no predictive value for loosing implant stability can be attributed to RFA since the decrease occurred after the fact. PMID- 17355358 TI - Is laparoscopically assisted radical vaginal hysterectomy for cervical carcinoma safe? A case control study with follow up. AB - OBJECTIVE: To compare a new surgical approach, laparoscopically assisted radical vaginal hysterectomy (LARVH) with open radical hysterectomy in women with cervical cancer. Can selected women benefit from the minimally invasive approach without compromising safety (recurrence rate) and morbidity (complications)? DESIGN: Retrospective case control study. SETTING: A tertiary referral unit for gynaecological malignancies. POPULATION: Thirty women undergoing LARVH were included and compared with 30 women undergoing open radical surgery. The control group was matched for age, body mass index and disease stage. METHODS: Retrospective collection of data from patient files and follow up. MAIN OUTCOME MEASURES: Recurrence rate, complication rate, hospital stay, nodal counts, blood loss, operating time. RESULTS: Recurrence rates were equal (6.7%). There was one death, in the LARVH group. Follow up was mean 31 months in the LARVH group and 30.9 months in the open group. Blood loss as measured by mean drop in haemoglobin was greater in the open group (2.03 versus 3.01 g/dl, P = 0.02). Transfusions were given in 40% of women in the open group and 16.7% in the LARVH group. Hospital stay was significantly less in the LARVH group (5.9 versus 7.8 nights, P = 0.003). Mean operating time was longer in the LARVH group (131 versus 187 minutes P = 0.0001). Mean nodal counts did not differ significantly (17.4 in open vs 14.8 in LARVH, P > 0.05). There were seven perioperative complications in the open group and four in the LARVH group. There have been two recurrences in each group (6.67%) at mean follow up of 31 (LARVH) and 30.9 (open) months. CONCLUSIONS: The first 30 LARVH procedures performed in this unit are comparable in terms of safety (recurrence rate and complication rate) and economic factors (shorter hospital stay mitigating longer operating time). Further development of this technique is warranted. PMID- 17355359 TI - Cost-effectiveness of antenatal screening for neonatal alloimmune thrombocytopenia. AB - OBJECTIVES: To estimate the costs and health consequences of three different screening strategies for neonatal alloimmune thrombocytopenia (NAIT). DESIGN: Cost-utility analysis on the basis of a decision tree that incorporates the relevant strategies and outcomes. SETTING: Three health regions in Norway encompassing a 2.78 million population. POPULATION: Pregnant women (n = 100,448) screened for human platelet antigen (HPA) 1a and anti-HPA 1a antibodies, and their babies. METHOD: Decision tree analysis. In three branches of the decision tree, pregnant women entered a programme while in one no screening was performed. The three different screening strategies included all HPA 1a negative women, only HPA 1a negative, HLA DRB3*0101 positive women or only HPA 1a negative women with high level of anti-HPA 1a antibodies. Included women underwent ultrasound examination and elective caesarean section 2-4 weeks before term. Severely thrombocytopenic newborn were transfused immediately with compatible platelets. MAIN OUTCOME MEASUREMENTS: Quality-adjusted life years (QALYs) and costs. RESULTS: Compared with no screening, a programme of screening and subsequent treatment would generate between 210 and 230 additional QALYs among 100,000 pregnant women, and at the same time, reduce health care costs by approximately 1.7 million euros. The sensitivity analyses indicate that screening is cost effective or even cost saving within a wide range of probabilities and costs. CONCLUSION: Our calculations indicate that it is possible to establish an antenatal screening programme for NAIT that is cost effective. PMID- 17355360 TI - Tolerability and efficacy of duloxetine in a nontrial situation. AB - OBJECTIVE: To assess the tolerability and efficacy of duloxetine in a nontrial situation. DESIGN: Prospective observational study. SETTING: Urogynaecology Unit, District General Hospital, UK. POPULATION: Two hundred and twenty-two women with a diagnosis of urodynamic stress incontinence (USI) or mixed USI and detrusor overactivity (DOA) took duloxetine for 4 weeks. METHODS: The results of therapy were assessed with a Patient Global Impression of Improvement (PGI-I) questionnaire. One hundred and forty-eight (67%) women were initially treated with 40 mg twice a day, 67 (30%) women were treated with an escalating dose initially at 20 mg twice a day increasing to 40 mg twice a day after 2 weeks and seven (3%) women were started on a dose of 20 mg twice a day which they continued. MAIN OUTCOME MEASURES: Discontinuation rates and PGI-I scores. RESULTS: Overall 146/222 (66%) women discontinued therapy due to adverse effects or lack of efficacy. Significantly more women starting on the 40 mg twice a day dose stopped due to adverse effects when compared with the escalating dose (P < 0.025). Of the women who tolerated therapy, 80 out of 120 (67%) had a PGI-I score indicating an improvement. However, the overall rate of improvement was 37%. PGI I scores and discontinuation rates were not significantly different between the group with USI and the group with mixed USI and DOA (P > 0.05). CONCLUSION: In a nontrial situation duloxetine is poorly tolerated. Introducing an escalating dose may improve tolerability. A similar number of women with USI and mixed incontinence had a PGI-I score indicating improvement. PMID- 17355361 TI - Uterine compression sutures for postpartum bleeding with uterine atony. AB - OBJECTIVE: To assess the efficacy of a new uterine compression suturing technique in reducing postpartum haemorrhage secondary to severe uterine atony. DESIGN: Retrospective study. SETTING: University hospital between December 2000 and March 2006. POPULATION: Twenty women with uterine atony and postpartum bleeding that did not react to usual medical management. METHODS: All these women underwent compression suturing of the uterus, in which the anterior and posterior walls of the uterus were attached so as to compress the uterus. MAIN OUTCOME MEASURES: Arrest of the bleeding, complications and fertility. RESULTS: Uterine compression suturing was sufficient to stop the bleeding immediately in 95% of the women. None of the women developed complications related to the procedure. All the women recovered normal menstrual cycles. Since uterine compression suturing, eight women have tried to conceive and six (75%) have had a term delivery. CONCLUSION: Uterine compression suturing is a simple conservative procedure to stop postpartum haemorrhage in the case of failure of the usual management. This surgical technique can be performed quickly and does not seem to decrease fertility. PMID- 17355362 TI - A longitudinal observational study of preference for elective caesarean section among nulliparous Hong Kong Chinese women. AB - OBJECTIVE: To establish whether women's preference for elective caesarean section (ELCS) changes as gestation advances. DESIGN: A prospective longitudinal observational study. SETTING: Two units providing obstetric care in Hong Kong, one public and one private. SAMPLE: Five hundred and one nulliparous Chinese pregnant women attending their routine fetal anomaly scan in either unit. METHODS: Consented subjects had two interviews using a structured questionnaire at 18-22 weeks and 35-37 weeks of gestation, respectively. Multivariate analysis was performed to identify determinants for preferring ELCS at the two gestational ages. MAIN OUTCOME MEASURE: The preferences for the mode of delivery at the two gestational ages. RESULTS: The prevalence of maternal preference for ELCS in the study cohort was 17.2% (95% CI 13.9-20.5) and 12.7% (95% CI 9.6-15.8) at mid trimester and at term, respectively. Significantly more women who preferred ELCS at mid-trimester changed to a trial of vaginal delivery (VD) at term than vice versa (42.0 versus 3.8%). The partner's preference for ELCS was a significant determinant for women preferring ELCS throughout the antenatal period. Among the women booked in the public sector, more women who preferred ELCS at term changed to deliver in private hospitals than those who preferred VD (46.2 versus 9.7%). CONCLUSIONS: Many women changed from preferring ELCS to preferring VD as their pregnancy approached term. The partner's preference was a significant determinant for the women's choice. If a decrease in the proportion of women preferring ELCS is desired, the intervention programme should target the women and their partners who hold such a preference at 20 weeks. PMID- 17355363 TI - Soft tissue healing at titanium implants coated with type I collagen. An experimental study in dogs. AB - OBJECTIVE: To analyse the soft tissue healing at titanium implants coated with type 1 collagen. MATERIAL AND METHODS: Six dogs were used. The mandibular pre molars and the three anterior maxillary pre-molars were extracted. Three months later mucoperiosteal flaps were raised and two test and two control implants were installed (3i TG Osseotite 3.75 x 10 and 2.8 mm transmucosal collar). The test implants were coated with a purified porcine type I collagen. Cover screws were placed and flaps were sutured. The sutures were removed 2 weeks later and a plaque-control programme was initiated. Another 2 weeks later, the procedure was repeated in the contra-lateral mandibular region. Four weeks after the second implant surgery, biopsies were obtained and prepared for histological examination. RESULTS/CONCLUSION: The vertical dimensions of the epithelial and connective tissue components as well as the composition of the connective tissue portion facing the implant were similar at collagen-coated and uncoated implants after 4 and 8 weeks of healing. It is suggested that soft tissue healing to implants coated with type I collagen was similar to that at non-coated titanium implants and that no adverse reactions to the collagen-coated implants occurred. PMID- 17355364 TI - Association of height with inflammation and periodontitis: the Study of Health in Pomerania. AB - AIM: Short stature in adulthood has been associated with increased risk of health problems. Predisposition to inflammatory diseases might be associated with impaired length growth and impose a lifelong inflammatory burden. We tested this hypothesis in a cross-sectional population-based study with respect to periodontitis. MATERIAL AND METHODS: IN 4290 randomly selected subjects from the normal population, we determined anthropometric measures and diagnostic periodontal parameters. Behavioural and environmental risk factors were assessed by interviews and questionnaires. RESULTS: In regression analyses adjusted for age, gender, smoking, diabetes, education, and dental appointments, an inverse association was observed between height and clinical attachment loss. The magnitude of the association was higher in presence of risk factors smoking or diabetes. Odds ratios for smoking were 3.5 (2.2-5.7%, 95% confidence interval) and 2.6 (1.5-4.3%) with the shortest and tallest height quartile, respectively. Figures for diabetes were 1.37 (1.04-1.80%) and 0.97 (0.67-1.39%), respectively. Stratification for age and gender revealed that taller subjects had less periodontitis and decreased concentrations of markers of systemic inflammation than their shorter counterparts. CONCLUSION: This study is the first to associate height with periodontitis concluding that individuals born with a high susceptibility to infectious and inflammatory diseases may suffer from such diseases in childhood whereby the length growth could be impaired. Reaching adulthood, growth comes to a halt but the individual remains susceptible to inflammatory sequelae. Thus, smaller persons pertain a tendency to more severe periodontitis. PMID- 17355365 TI - Gingival crevicular fluid levels of RANKL and OPG in periodontal diseases: implications of their relative ratio. AB - AIM: Receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) are a system of molecules that regulate bone resorption. This study aims to compare the levels of RANKL, OPG and their relative ratio in gingival crevicular fluid (GCF) of healthy and periodontal disease subjects. MATERIAL AND METHODS: GCF was obtained from healthy (n=21), gingivitis (n=22), chronic periodontitis (n=28), generalized aggressive periodontitis (n=25) and chronic periodontitis subjects under immunosuppressant therapy (n=11). RANKL and OPG concentrations in GCF were measured by enzyme-linked immunosorbent assays. RESULTS: RANKL levels were low in health and gingivitis groups, but increased in all three forms of periodontitis. OPG levels were higher in health than all three periodontitis, or gingivitis groups. There were no differences in RANKL and OPG levels between chronic and generalized aggressive periodontitis groups, whereas these were lower in the immunosuppressed chronic periodontitis group. The RANKL/OPG ratio was significantly elevated in all three periodontitis forms, compared with health or gingivitis, and positively correlated to probing pocket depth and clinical attachment level. CONCLUSION: GCF RANKL and OPG levels were oppositely regulated in periodontitis, but not gingivitis, resulting in an enhanced RANKL/OPG ratio. This ratio was similar in all three periodontitis groups and may therefore predict disease occurrence. PMID- 17355366 TI - Different prostate-specific antigen assays give different results on the same blood sample: an obstacle to recommending uniform limits for prostate biopsies. AB - OBJECTIVE: To show the effect of different results for total prostate specific antigen (tPSA) and percentage free/total PSA (%fPSA) obtained with different assays for differentiating between benign and malignant prostate diseases. PATIENTS AND METHODS: Data were used for tPSA and fPSA levels from 596 patients with prostate cancer (314) or no evidence of cancer (282) within the PSA range 0.5-10 ng/mL, analysed with assays from Abbott (AxSYM), Beckman Coulter (Access), DPC (Immulite 2000), and Roche (Elecsys 2010), and with tPSA and complexed PSA (cPSA) assays from Bayer (ADVIA Centaur), as already reported. Receiver operating characteristics (ROC), specificities at assay-dependent and fixed thresholds, and the percentages of correct classification rates of patients were calculated. RESULTS: Whereas the areas under the ROC curves were no different among all tPSA assays, the assay-specific thresholds at 90% sensitivity were 2.5-3.1 ng/mL. When using fixed 2.5 or 4 ng/mL tPSA thresholds there was a wide sensitivity range, with significant differences among almost all assays, resulting in significantly different classification rates of patients. These differences were even larger when using fixed %fPSA thresholds. CONCLUSIONS: The current situation of differences among PSA values measured with different assays do not allow the recommendation of uniform PSA limits as biopsy criteria. For that purpose, better harmonization of PSA values between the different PSA test systems must be realized. PMID- 17355367 TI - Radiotelemetered urodynamics of obstructed ovine fetal bladders: correlations with ex vivo cystometry and renal histopathology. AB - OBJECTIVE: To test the hypothesis that fetal bladder outlet obstruction (BOO) in sheep causes abnormal urodynamics correlating with the initiation of renal pathology, as most boys with posterior urethral valves (PUV) have bladder dysfunction when assessed after birth. MATERIALS AND METHODS: Male ovine fetuses at 94 days of gestation were assigned to BOO (four) or sham control (five) groups. In BOO fetuses, radiotelemetry catheters were inserted transurachally and intraperitoneally, and the urethra was partly occluded. In two sham controls catheters were inserted directly through the bladder wall; the remaining three had sham surgery only. Radiotelemetered cystometry was recorded daily where possible. At the end of the experiment (9 days), ex vivo cystometry, bladder contractility studies and renal tract histology were assessed. RESULTS: Ultrasonography showed dilated renal tracts only in BOO fetuses; three of four BOO fetuses had renal cortical cysts. The control fetuses with bladder catheters died in utero, so urodynamics were recorded only in fetuses with BOO. The baseline filling/storage detrusor pressures increased slightly (by a mean of 5 mmHg) during the first 4 days of BOO, thereafter returning to those at the outset. There were marked changes in the patterns of bladder activity from 1 to 9 days. The frequency and duration of 'voiding' increased; as such the higher sustained pressures of emptying activity were progressively extended and the periods of low pressure filling/storage accordingly shortened. The patterns among individual fetuses with BOO were not substantially different, except that the one with the non-cystic kidneys had a more moderate frequency and duration of voiding. Ex vivo compliance and contractility showed no consistent differences in detrusor compliance or contractility between BOO and sham bladders. CONCLUSION: In this fetal model of PUV, there was a progressive increase in the duration and frequency of sustained elevated 'voiding' pressures, with no change in bladder compliance. Fetal kidneys were sensitive to these altered dynamics, with the formation of cortical cysts by 9 days after initiating BOO. PMID- 17355368 TI - Contrast-enhanced ultrasonography in the follow-up of cryoablation of renal tumours: a feasibility study. AB - OBJECTIVE: To determine whether evaluating perfusion patterns with contrast enhanced ultrasonography using contrast-pulse sequence imaging (CPS; a new imaging method that enables selective visualization of perfusion) is possible at different times after cryoablation of renal tumours, and to describe the characteristics of CPS in a small group of patients. PATIENTS AND METHODS: The efficacy of renal cryoablation is mainly judged using imaging. Seven randomly selected patients, each at a different time after laparoscopically assisted cryoablation of a renal tumour, were investigated with CPS and a microbubble contrast agent. The perfusion characteristics in the lesions were scored by two investigators and described, and the lesions were measured. RESULTS: In the seven patients treated with cryoablation for small renal tumours, eight CPS studies were performed. Five lesions showed no enhancement and one lesion, investigated 18 months after treatment was not recognized. In one patient, no enhancement was seen after 1 month but 7 months later, there were minimal contrast signals inside the treated area. The lesions could be measured with a mean standard deviation of 1.1 mm and a mean difference between the two investigators of 0.7 mm. CONCLUSION: Our first experiences with CPS imaging for the follow-up of renal cryoablation show that this technique can be used to characterize perfusion defects at different times after cryoablation. PMID- 17355369 TI - Long-term follow-up of a neoadjuvant chemohormonal taxane-based phase II trial before radical prostatectomy in patients with non-metastatic high-risk prostate cancer. AB - OBJECTIVE: To assess the feasibility and activity of a neoadjuvant treatment combining a luteinizing hormone-releasing hormone (LHRH)-analogue, estramustine and docetaxel before radical retropubic prostatectomy (RRP) in patients with high risk prostate cancer. PATIENTS AND METHODS: High-risk patients were defined as clinical stage > or =T3 and/or a prostate-specific antigen (PSA) level of > or =15 ng/mL, and/or biopsy a Gleason sum of > or =8. Patients received LHRH analogue treatment until the PSA nadir (a stable PSA level for two consecutive determinations) and then, continuing hormone therapy, a combined regimen of estramustine and docetaxel. Patients had RRP within a month of completing the neoadjuvant regimen. All patients were assessed for toxicity and surgical complications. A clinical response was defined as complete (CR, the disappearance of all palpable and radiological abnormalities and a decline in PSA level of > or =90%) or partial (PR, a decline in PSA level of half or more with stable or improved palpable and/or radiological abnormalities). A pathological response was defined as 'complete' (undetectable cancer), 'substantial' (residual cancer in < or =10% of the surgical specimen) or 'minimal' (residual cancer in >10% of the surgical specimen). The biomarkers p53, bcl-2, MIB1, erbB2 and factor VIII were also evaluated. RESULTS: Of 22 patients enrolled between March 1999 and January 2002, 21 (mean age 63 years; mean PSA level 61 ng/mL; median biopsy Gleason sum 8) completed the neoadjuvant therapy. The clinical stage was organ-confined in three patients (15%); five (25%) had pelvic lymphadenopathy on computed tomography. The neoadjuvant treatment was well tolerated, with only one grade 2 toxicity (Eastern Cooperative Oncology Group grading). All PSA values decreased by >90% from baseline after hormonal therapy only, and the mean reduction from before to after chemotherapy was statistically significant (P = 0.001). Three patients (15%) had a CR, 16 (80%) had a PR and one (5%), with sarcomatoid tumour, had progression; 19 had non-nerve-sparing RRP and there were no major complications during or after RRP. The pathological assessment showed that one patient (5%) had no tumour (pT0) and six (32%) had a 'substantial' response. The overall rate of organ-confined disease was 58%, vs a mean 8% predicted likelihood from the Kattan nomogram. Five patients (26%) had positive surgical margins and four (21%) had positive lymph nodes. At a median follow-up of 53 months, eight patients (42%) were disease-free. Organ-confined disease (P = 0.022), residual cancer at pathology in < or =10% of the surgical specimen (P = 0.007) and no seminal vesicle invasion (P = 0.001) correlated with disease-free survival. CONCLUSION: A neoadjuvant chemohormonal regimen before RRP is feasible and active in patients with high-risk prostate cancer. The rate of pathological organ confined disease was higher than expected and responding patients had an 85% disease-free survival rate at 5 years. PMID- 17355370 TI - Economic conditions and marriage quality of men with prostate cancer. AB - OBJECTIVE: To explore the predictors of the quality of marriage of men with prostate cancer, as being diagnosed with prostate cancer affects the quality of life of the man and his partner, and while some aspects are known about the impact of the disease and its treatments on the man's quality of life, less is known about the marriage quality (MQ) in this new situation. PATIENTS AND METHODS: We followed 591 men from Stockholm County (Sweden) who had been diagnosed with prostate cancer in 1999, and who were 50-80-years old and alive on 1 October 2002. The men completed a questionnaire asking about their MQ, and several other sociodemographic, medical and economic characteristics. RESULTS: Of 426 men who provided information and who had a spouse or partner, 168 (39.4%) reported having a lower MQ due to their disease. Increased expenditure (46.2% vs 30.9%; relative risk, 1.5; 95% confidence interval, 1.1-2.0) and decreased income (55.4% vs 36.5%; 1.5, 1.1-2.0) as a consequence of prostate cancer reduced their MQ. Patients who had erectile dysfunction had a lower MQ (46.3% vs 11.8%; 3.9; 2.0-7.6). There was also a lower MQ in men who were depressed or had urinary leakage as a consequence of prostate cancer. Younger men (50-69 years old) with prostate cancer had a lower MQ than older men (70-80 years; 51.9% vs 33.1%; 1.6; 1.2-2.0). CONCLUSIONS: Men whose economic situation is worsened by prostate cancer reported having a reduced MQ. There was also such an effect for men with erectile dysfunction, urinary leakage and depression, and among men diagnosed with prostate cancer when young. PMID- 17355371 TI - Penile size and the 'small penis syndrome'. AB - The male is often troubled by concerns that his penis is not large enough to satisfy his partner or himself. He is ashamed to have others view his penis, especially in the flaccid state. Such concerns might be unfounded in reality and might be a presentation of social anxiety or some other clinical problem, such as erectile dysfunction. Concern over the size of the penis, when such concern becomes excessive, might present as the 'small penis syndrome', an obsessive rumination with compulsive checking rituals, body dysmorphic disorder, or as part of a psychosis. However, it is often a worry that can be described as within the normal experience of many men. Various potential causal factors are considered. A thorough assessment, normalizing the worry and then exploring the treatment options in detail with the man, is essential to allow the matter to be consolidated satisfactorily within the male ego. PMID- 17355372 TI - Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1alpha. AB - OBJECTIVES: To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1alpha to the erectile compartment on erectile function in a rat model of diabetes. MATERIALS AND METHODS: Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMVbetagal or AdCMVPKG1alpha, in 10 rats each) 2 months after the induction of DM. Intracavernosal pressure (ICP) during stimulation of the cavernosal nerve (CN) was assessed, and compared with mean arterial pressure (MAP). Erectile tissue was harvested for Western blot analysis, immunohistochemistry and total PKG activity. Ten age-matched rats without DM served as the control. RESULTS: Compared to controls, AdCMVbetagal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1alpha, peak ICP, ICP/MAP ratios and filling rates were significantly better than in DM rats transfected with the reporter gene. As assessed by Western blot and immunohistochemistry, expression of PKG1alpha and PKG1beta was lower in corporal tissue from DM AdCMVbetagal transfected rats than in controls. PKG1alpha expression was improved after AdCMVPKG1alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control. CONCLUSION: PKG1alpha and PKG1beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy. PMID- 17355373 TI - 11C-choline positron-emission tomography/computed tomography and transrectal ultrasonography for staging localized prostate cancer. AB - OBJECTIVE: To evaluate and compare the role of (11)C-choline positron emission tomography (PET) and transrectal ultrasonography (TRUS) in the preoperative staging of clinically localized prostate cancer. PATIENTS AND METHODS: Fifty-five consecutive patients with biopsy-confirmed prostate cancer had TRUS and (11)C choline PET as a part of their clinical staging programme before radical retropubic prostatectomy (RP). The PET images were prospectively interpreted by a consensus decision of two nuclear medicine physicians and one radiologist with special expertise in the field. The TRUS was done by one experienced urologist. The criteria evaluated prospectively in each patient were extracapsular extension (ECE), seminal vesicle invasion (SVI) and bladder neck invasion (BNI). The results were compared with the histopathological findings after RP. RESULTS: At pathology, 32 patients were classified pT2, 16 as pT3a and three had pT3b lesions. In four patients the histopathological examination showed pT4 with BNI. The overall accuracy of PET in defining local tumour stage (pT2 and pT3a-4) was 70%; the overall accuracy by TRUS was 26%. PET was more sensitive than TRUS for detecting ECE (pT3a) and SVI (pT3b) in advanced stages, and in pT4 stages. The sensitivity and positive predictive value (PPV) (95% confidence interval) in stages pT3a-pT4 for PET were 36 (17-59)% and 73 (39-89)%. The sensitivity and PPV in stages pT3a-pT4 for TRUS were 14 (3-35)% and 100 (29-100)%. CONCLUSIONS: (11)C choline PET and TRUS tended to understage prostate cancer. This series shows the current limited value of TRUS and PET for making treatment decisions in patients with clinically localized prostate cancer, especially if a nerve-sparing RP is considered. Treatment decisions should not be based on TRUS and (11)C-choline PET findings alone. In future studies, the combination of metabolic and anatomical information of PET and endorectal magnetic resonance imaging should be evaluated, as this might optimize the preoperative staging in prostate cancer. PMID- 17355376 TI - Abortion among young women and subsequent life outcomes. AB - CONTEXT: Young women frequently cite concerns about the effects of unplanned pregnancies on future life course outcomes, including education, employment and relationships, as reasons for seeking abortion. There is relatively little evidence as to whether abortion leads to improved life course outcomes for young women who choose this option. METHODS: Data from 492 women participating in a 25 year longitudinal study of a New Zealand birth cohort were used in regression models that examined the relationship between pregnancy and abortion history prior to age 21 and selected social and economic outcomes at ages 21-25. RESULTS: Compared with young women who became pregnant before age 21 but did not seek an abortion, young women who had an abortion had significantly better outcomes on six out of 10 measures spanning education, income, welfare dependence and domestic violence. Adjustment for confounding factors indicated that most of these differences were explained by family, social and educational characteristics that were present prior to pregnancy. Nonetheless, even after adjustment for confounding factors, young women who had abortions had higher levels of subsequent educational achievement than those who became pregnant but did not have abortions. CONCLUSIONS: Abortion may mitigate some effects of early unplanned pregnancy. However, further study of its potential risks and benefits is needed so that women can make fully informed decisions as to whether to terminate unintended pregnancies. PMID- 17355377 TI - Identifying barriers to emergency contraception use among young women from various sociocultural groups in British Columbia, Canada. AB - CONTEXT: Despite advances related to the provision of emergency contraception in Canada, particularly the granting of independent prescriptive authority to pharmacists in 2000, little is known about the ways in which women perceive potential barriers to using it. METHODS: In 2004, an ethnically diverse sample of 52 women living in Greater Vancouver participated in interviews that were analyzed for an assessment of women's knowledge, attitudes and experiences related to emergency contraception, with particular attention to the ways in which ethnicity affected their stories. RESULTS: Participants generally misperceived emergency contraception as an abortifacient, and often mistakenly thought that it has long-term effects on health and fertility. Knowledge gaps regarding reproductive physiology impeded clear understanding of when it is most effective. Participants also reported receiving subtle and sometimes overtly stigmatizing messages from providers when they sought emergency contraception. Asian and South Asian women were particularly concerned about negative interactions with providers; for example, they feared that female providers from their sociocultural community might recognize, chastise or gossip about them. Institutional policies (e.g., a Catholic hospital's refusal to provide the method), coupled with low awareness of pharmacists' prescriptive authority, also created barriers to use. CONCLUSIONS: Women's ability to benefit from emergency contraception is hampered by lack of knowledge and conservative cultural or social mores. Serious contextual and structural shifts are required before woman centered approaches to provision of the method become the norm. PMID- 17355378 TI - Pregnancy and STD prevention counseling using an adaptation of motivational interviewing: a randomized controlled trial. AB - CONTEXT: Given levels of unintended pregnancy and STDs, an effective counseling intervention is needed to improve women's consistent use of effective prevention methods. METHODS: A sample of 764 women aged 16-44 who were at risk of unintended pregnancy were enrolled in a randomized controlled trial in North Carolina in 2003-2004. Intervention participants received pregnancy and STD prevention counseling, adapted from motivational interviewing, both at enrollment and two months later; controls received only a session of general health counseling. Levels of contraceptive use (categorized as high, low or none on the basis of the effectiveness of the method and the consistency of use) and barriers to use were measured at two, eight and 12 months; chi-square tests were used to compare selected outcomes between the groups. Rates of unintended pregnancy and chlamydia infection were assessed over the study period. RESULTS: At baseline, 59% of all participants reported a high level of contraceptive use, 19% a low level and 22% nonuse. At two months, the proportions of intervention and control participants who had improved their level of use or maintained a high level (72% and 66%, respectively) were significantly larger than the proportions who had reported a high level of use at baseline (59% and 58%, respectively). No significant differences were found between the groups at 12 months, or between baseline and 12 months for either group. During the study, 10-11% of intervention and control participants became pregnant, 1-2% received a chlamydia diagnosis and 7-9% had another STD diagnosed. CONCLUSIONS: Repeated counseling sessions may be needed to improve contraceptive decision-making and to reduce the risk of unintended pregnancy and STDs. PMID- 17355379 TI - Multipartnered fertility among young women with a nonmarital first birth: prevalence and risk factors. AB - CONTEXT: Although early nonmarital fertility has been well studied, less attention has been paid to the subsequent fertility of young unwed mothers. In particular, the frequency with which these young women have subsequent births with a new partner (multipartnered fertility) and the risk factors associated with doing so are unknown. METHODS: The proportion of young women who had a first birth and the proportion who subsequently had a child with a new partner were determined among a sample of participants in Waves 1 (1995) and 3 (2001-2002) of the National Longitudinal Study of Adolescent Health. Multivariate analyses identified characteristics associated with multipartnered fertility. RESULTS: By Wave 3, when these young women were 19-25 years old, 29% had had a first birth, and 3% had had births with multiple partners. Among women with a nonmarital first birth, 14% subsequently had a birth with another partner, and 41% with two or more children had had multiple partners. The prevalence of multipartnered fertility differed sharply by race and ethnicity. Most new-partner births occurred outside of marriage, especially among black women. Respondents who had no contact with their partner after informing him of their first pregnancy or who had not wanted to have a child with him had an increased likelihood of multipartnered fertility. CONCLUSIONS: The context in which first births occur sets the stage for subsequent childbearing. Programs that help women avoid having births in unfavorable circumstances, such as in early and unstable relationships, may reduce the prevalence of multipartnered fertility. PMID- 17355380 TI - Social ecological predictors of repeat adolescent pregnancy. AB - CONTEXT: Women with multiple pregnancies in adolescence may experience medical, psychological and social complications. Improved understanding of the individual , dyad-, family-, peer/community- and social system-level risk factors for repeat pregnancy may lead to the development of more effective prevention strategies for adolescent mothers in a variety of settings. METHODS: Between 1993 and 1996, white, black and Mexican American adolescent mothers at a labor and delivery unit in Texas were interviewed after delivery and completed written surveys prospectively for up to 48 months. Logistic regression analyses were used to determine predictors of repeat pregnancy within 24 months, using social ecological theory as a guide. RESULTS: Forty-two percent of adolescent mothers experienced a repeat pregnancy within 24 months; 73% of these delivered a second child. Individual-level predictors were planning to have another baby within five years (odds ratio, 1.6) and not using long-acting contraceptives within three months of delivery (2.4). Dyad-level predictors were not being in a relationship with the father of the first child three months after delivery (2.0), being more than three years younger than the first child's father (1.6) and experiencing intimate partner violence within three months after delivery (1.9). Peer/community-level predictors were not being in school three months postpartum (1.8) and having many friends who were adolescent parents (1.5). CONCLUSION: Adolescent mothers are at high risk for a rapid subsequent pregnancy. Interventions that address the complex and multifaceted aspects of the lives of adolescent mothers are needed to prevent repeat pregnancy. PMID- 17355381 TI - U.S. women's one-year contraceptive use patterns, 2004. AB - CONTEXT: Unintended pregnancies occur far too often in the United States, and half occur when couples fail to practice contraception. Improved measures of the continuity of women's contraceptive use, nonuse and switching patterns can help identify ways to reduce unintended pregnancy. METHODS: A nationally representative sample of 1,978 adult women at risk of unintended pregnancy was surveyed by telephone in 2004. Respondents provided detailed information about contraceptive use and periods of stopping or switching methods during the past year. A typology of patterns of contraceptive use was created, classifying women into mutually exclusive categories according to their exposure to pregnancy risk. RESULTS: Twenty-three percent of women at risk of unintended pregnancy were exposed to a high risk of pregnancy because of gaps in contraceptive method use in the year prior to the survey--8% were consistent nonusers, and 15% experienced 1-11 months of nonuse while at risk. More than half of women used a method during each of the previous 12 months-38% used the same method or methods all year, and 24% switched methods. Fifteen percent of women had gaps in contraceptive use when they were not at risk. Women reported a variety of reasons for their gaps in contraceptive use, including method-related difficulties and side effects, infrequent sex and being ambivalent about avoiding pregnancy. CONCLUSIONS: Strategies for reducing gaps in contraceptive use include improved counseling to help women both choose the right method and continue method use, especially when they have periods of infrequent sexual activity or are experiencing method related side effects or problems. PMID- 17355382 TI - Multipartnered fertility: can it be reduced? PMID- 17355390 TI - Definition of the USDA103 strain of channel catfish (Ictalurus punctatus). AB - Although there are differences in performance between genetic groups of channel catfish, identification and management of these groups is difficult because catfish strains look alike and individuals cannot be tagged efficiently. Thus, US catfish producers have not been able to objectively identify fish from different strains or populations, and it has been difficult for them to maintain the genetic purity of populations on the farm. We have developed a multiplexed microsatellite genotyping system to define catfish populations based on allelic frequency and exclusion. A commercial catfish genotype database was developed using catfish samples collected from 24 processing plants in the four main US catfish-producing states. The utility of the system was tested by the molecular characterization of the USDA103 research strain. Using eight microsatellite loci, the probability of falsely classifying an individual non-USDA103 catfish as a USDA103 was 0.0065. From a sample of 50 fish from a putative USDA103 pond, the probability of falsely including two non-USDA103 fish was 1 x 10(-105), and the conservative probability of falsely excluding two USDA103 fish was 1 x 10(-6). This genotyping system provides channel catfish producers with an objective mechanism for identification and management of genetically selected fish. PMID- 17355391 TI - Development of a model for mapping cryptorchidism in sheep and initial evidence for association of INSL3 with the defect. PMID- 17355392 TI - Assignment of 58 genes from HSA18 to the porcine IMpRH maps for SSC1 and SSC6. PMID- 17355393 TI - Assignment of 56 genes from HSA13q to the porcine IMpRH map. PMID- 17355394 TI - Quantitative effects of an intronic retroviral insertion on the transcription of the tyrosinase gene in recessive white chickens. AB - Recently, we reported the complete association of a retroviral insertion in intron 4 of the tyrosinase gene and the recessive white mutation (c) in chickens. The mutant allele carrying the retroviral insertion produced, in skin samples of 10-week-old chickens, aberrant tyrosinase transcripts that did not contain exon 5. In the present study, we performed serial molecular and statistical analyses on embryos and 10-week-old chickens to characterize the quantitative effect of the retroviral insertion on the expression pattern of tyrosinase in different tissues (skin and retina). By using quantitative real-time RT-PCR, we observed that the expression level of tyrosinase was significantly lower in recessive white chickens than in wild-type coloured chickens, but that this pattern was age and tissue-dependent. The differential expression in skin was not significant in embryos, whereas it was highly significant in 10-week-old chickens. Furthermore, there was no difference in the expression of tyrosinase in the retinal pigment epithelium of animals with different genotypes; this corresponds to phenotypic data, which show pigmented eyes in both genotypes. These findings show that the retroviral insertion disturbs tyrosinase expression in the recessive white mutant chickens, and suggests that the regulation of tyrosinase expression in chickens differs between embryos and growing animals, as well as between skin and retina. PMID- 17355395 TI - Functional consequences of RNA interference targeting COMMD1 in a canine hepatic cell line in relation to copper toxicosis. AB - A deletion in the copper metabolism (Murr1) domain containing 1 (COMMD1) gene is associated with hepatic copper toxicosis in dogs, yet evidence of copper retention in COMMD1-depleted hepatic cells has not been shown. In a dog hepatic cell line, we analysed the copper metabolic functions after an 80% (mRNA and protein) COMMD1 reduction with COMMD1-targeting siRNAs. Exposure to 64Cu resulted in a significant increase in copper retention in COMMD1-depleted cells. COMMD1 depleted cells were almost three times more sensitive to high extracellular copper concentrations. Copper-mediated regulation of metallothionein gene expression was enhanced in COMMD1-depleted cells. Based on the increased copper accumulation and enhanced cellular copper responses upon COMMD1 reduction, we conclude that COMMD1 has a major regulatory function for intracellular copper levels in hepatic cells. PMID- 17355396 TI - Nurturing resilient children. PMID- 17355397 TI - Neurodevelopmental sequelae of postnatal maternal care in rodents: clinical and research implications of molecular insights. AB - Parental care plays an important role in the emotional and cognitive development of the offspring. Children who have been exposed to abuse or neglect are more likely to develop numerous psychopathologies, while good parent-infant bonding is associated with improved resiliency to stress. Similar observations have also been reported in non-human primates and rodents, suggesting that at least some neurodevelopmental aspects of parent-offspring interactions are conserved among mammals and could therefore be studied in animals. We present data to suggest that frequency of licking and grooming provided by the dam during a critical period in development plays an important role in modifying neurodevelopment. These findings are examined in the broader context in which exposure to other sensory modalities such as vision or hearing during a specific period in development shapes brain development with functional consequences that persist into adulthood. We also discuss recent rodent work showing that increased frequency of licking and grooming provided by the dam during the first week of life is associated with changes in DNA methylation of promoter elements that control expression of these genes and behavior. The stability of DNA methylation in postmitotic cells provides a possible molecular scaffold by which changes in gene expression and behavioral traits induced by postnatal maternal care are maintained throughout life. Finally, the relevance of findings reported in rodents to those noted in non-human primates and humans are assessed and the research and clinical implications of these observations for future work are explored. PMID- 17355398 TI - Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? AB - We review a significant body of evidence from independent prospective studies that if a mother is stressed while pregnant, her child is substantially more likely to have emotional or cognitive problems, including an increased risk of attentional deficit/hyperactivity, anxiety, and language delay. These findings are independent of effects due to maternal postnatal depression and anxiety. We still do not know what forms of anxiety or stress are most detrimental, but research suggests that the relationship with the partner can be important in this respect. The magnitude of these effects is clinically significant, as the attributable load of emotional/behavioral problems due to antenatal stress and/or anxiety is approximately 15%. Animal models suggest that activity of the stress responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal end-product cortisol are involved in these effects in both mother and offspring. The fetal environment can be altered if stress in the mother changes her hormonal profile, and in humans, there is a strong correlation between maternal and fetal cortisol levels. However, many problems remain in understanding the mechanisms involved in this interaction. For example, maternal cortisol responses to stress decline over the course of pregnancy, and earlier in pregnancy, the link between maternal and fetal cortisol is less robust. It is possible that the effects of maternal anxiety and stress on the developing fetus and child are moderated by other factors such as a maternal diet (e.g., protein load). It is suggested that extra vigilance or anxiety, readily distracted attention, or a hyper-responsive HPA axis may have been adaptive in a stressful environment during evolution, but exists today at the cost of vulnerability to neurodevelopmental disorders. PMID- 17355400 TI - The parent-infant dyad and the construction of the subjective self. AB - Developmental psychology and psychopathology has in the past been more concerned with the quality of self-representation than with the development of the subjective agency which underpins our experience of feeling, thought and action, a key function of mentalisation. This review begins by contrasting a Cartesian view of pre-wired introspective subjectivity with a constructionist model based on the assumption of an innate contingency detector which orients the infant towards aspects of the social world that react congruently and in a specifically cued informative manner that expresses and facilitates the assimilation of cultural knowledge. Research on the neural mechanisms associated with mentalisation and social influences on its development are reviewed. It is suggested that the infant focuses on the attachment figure as a source of reliable information about the world. The construction of the sense of a subjective self is then an aspect of acquiring knowledge about the world through the caregiver's pedagogical communicative displays which in this context focuses on the child's thoughts and feelings. We argue that a number of possible mechanisms, including complementary activation of attachment and mentalisation, the disruptive effect of maltreatment on parent-child communication, the biobehavioural overlap of cues for learning and cues for attachment, may have a role in ensuring that the quality of relationship with the caregiver influences the development of the child's experience of thoughts and feelings. PMID- 17355401 TI - Parent-infant synchrony and the construction of shared timing; physiological precursors, developmental outcomes, and risk conditions. AB - Synchrony, a construct used across multiple fields to denote the temporal relationship between events, is applied to the study of parent-infant interactions and suggested as a model for intersubjectivity. Three types of timed relationships between the parent and child's affective behavior are assessed: concurrent, sequential, and organized in an ongoing patterned format, and the development of each is charted across the first year. Viewed as a formative experience for the maturation of the social brain, synchrony impacts the development of self-regulation, symbol use, and empathy across childhood and adolescence. Different patterns of synchrony with mother, father, and the family and across cultures describe relationship-specific modes of coordination. The capacity to engage in temporally-matched interactions is based on physiological mechanisms, in particular oscillator systems, such as the biological clock and cardiac pacemaker, and attachment-related hormones, such as oxytocin. Specific patterns of synchrony are described in a range of child-, parent- and context related risk conditions, pointing to its ecological relevance and usefulness for the study of developmental psychopathology. A perspective that underscores the organization of discrete relational behaviors into emergent patterns and considers time a central parameter of emotion and communication systems may be useful to the study of interpersonal intimacy and its potential for personal transformation across the lifespan. PMID- 17355402 TI - Programs for parents of infants and toddlers: recent evidence from randomized trials. AB - Programs for parents of young children hold considerable promise for improving children's life-course trajectories and for reducing health and development problems and associated costs to government and society. To date, this promise has not been achieved. Fulfilling the potential of parenting interventions will require substantial improvements in current practice for developing and testing such programs. Intervention development will be improved if clinicians and investigators ground parenting interventions in theory and epidemiology; and carefully pilot them to ascertain program feasibility, participant engagement, and behavioral change prior to testing them in randomized trials. Studies of parenting interventions will be improved if they adhere to the highest standards for randomization; if they examine objectively measured outcomes with clear public health relevance; and if they minimize selection factors known to compromise the analysis of data. Policy and practice recommendations for parenting interventions will be improved if they are based upon replicated randomized controlled trials, if the interventions are tested with different populations living in different contexts, and if they are examined in dissemination studies before public investments are made in such programs. Procedures need to be developed to ensure that the essential elements of evidence based parenting programs can be implemented reliably in a variety of practice settings so that they will produce their intended effects. To date, few programs have met these high programmatic and evidentiary standards, with the result that many large-scale policy initiatives for at-risk parents have failed. Evidence is accumulating, however, that some programs delivered by professionals, especially nurse home visiting programs for pregnant women and parents of young children, produce replicable effects on children's health and development, and that these programs can be reliably reproduced with different populations living in a variety of community settings. PMID- 17355399 TI - Brain basis of early parent-infant interactions: psychology, physiology, and in vivo functional neuroimaging studies. AB - Parenting behavior critically shapes human infants' current and future behavior. The parent-infant relationship provides infants with their first social experiences, forming templates of what they can expect from others and how to best meet others' expectations. In this review, we focus on the neurobiology of parenting behavior, including our own functional magnetic resonance imaging (fMRI) brain imaging experiments of parents. We begin with a discussion of background, perspectives and caveats for considering the neurobiology of parent infant relationships. Then, we discuss aspects of the psychology of parenting that are significantly motivating some of the more basic neuroscience research. Following that, we discuss some of the neurohormones that are important for the regulation of social bonding, and the dysregulation of parenting with cocaine abuse. Then, we review the brain circuitry underlying parenting, proceeding from relevant rodent and nonhuman primate research to human work. Finally, we focus on a study-by-study review of functional neuroimaging studies in humans. Taken together, this research suggests that networks of highly conserved hypothalamic midbrain-limbic-paralimbic-cortical circuits act in concert to support aspects of parent response to infants, including the emotion, attention, motivation, empathy, decision-making and other thinking that are required to navigate the complexities of parenting. Specifically, infant stimuli activate basal forebrain regions, which regulate brain circuits that handle specific nurturing and caregiving responses and activate the brain's more general circuitry for handling emotions, motivation, attention, and empathy--all of which are crucial for effective parenting. We argue that an integrated understanding of the brain basis of parenting has profound implications for mental health. PMID- 17355403 TI - In the best interests of society. AB - Each year, exposure to violent trauma takes its toll on the development of millions of children. When their trauma goes unaddressed, children are at greater risk for school failure; anxiety and depression and other post-traumatic disorders; alcohol and drug abuse, and, later in life, engaging in violence similar to that to which they were originally exposed. In spite of the serious psychiatric/developmental sequelae of violence exposure, the majority of severely and chronically traumatized children and youth are not found in mental health clinics. Instead, they typically are seen as the 'trouble-children' in schools or emerge in the child protective, law enforcement, substance abuse treatment, and criminal justice systems, where the root of their problems in exposure to violence and abuse is typically not identified or addressed. Usually, providers in all of these diverse service systems have not been sufficiently trained to know and identify the traumatic origins of the children's presenting difficulties and are not sufficiently equipped to assist with their remediation. This multiplicity of traumatic manifestations outside the mental health setting leads to the inescapable conclusion that we are dealing with a supra-clinical problem that can only be resolved by going beyond the child's individual clinical needs to enlist a range of coordinated services for the child and the family. This paper will focus on domestic violence as a paradigmatic source of violent traumatization and will (a) describe the impact and consequences of exposure to violence on children's immediate and long-term development; (b) examine the opportunities for, as well as the barriers to, bridging the clinical phenomena of children's violent trauma and the existing systems of care that might best meet their needs; and (c) critique current national policies that militate against a more rational and coherent approach to addressing these needs. PMID- 17355405 TI - Outcomes-focused knowledge translation: a framework for knowledge translation and patient outcomes improvement. AB - BACKGROUND: Regularly accessing information that is current and reliable continues to be a challenge for front-line staff nurses. Reconceptualizing how nurses access information and designing appropriate decision support systems to facilitate timely access to information may be important for increasing research utilization. DESCRIPTION OF STRATEGY: An outcomes-focused knowledge translation framework was developed to guide the continuous improvement of patient care through the uptake of research evidence and feedback data about patient outcomes. The framework operationalizes the three elements of the PARIHS framework at the point of care. Outcomes-focused knowledge translation involves four components: (a) patient outcomes measurement and real-time feedback about outcomes achievement; (b) best-practice guidelines, embedded in decision support tools that deliver key messages in response to patient assessment data; (c) clarification of patients' preferences for care; and (d) facilitation by advanced practice nurses and practice leaders. In this paper the framework is described and evidence is provided to support theorized relationships among the concepts in the framework. IMPLICATIONS: The framework guided the design of a knowledge translation intervention aimed at continuous improvement of patient care and evidence-based practice, which are fostered through real-time feedback data about patient outcomes, electronic access to evidence-based resources at the point of care, and facilitation by advanced practice nurses. The propositions in the framework need to be empirically tested through future research. PMID- 17355406 TI - Development and testing of a DVT risk assessment tool: providing evidence of validity and reliability. AB - BACKGROUND: Hospital-acquired deep vein thrombosis (DVT) and pulmonary embolisms (PE) are preventable problems that can increase mortality. Early assessment and recognition of risk as well as initiating appropriate prevention measures can prevent DVT or PE. AIMS: The purpose of this research project was to develop a DVT risk assessment tool and test the tool for validity and reliability. METHODS: Three phases were undertaken in developing and testing the JFK Medical Center DVT risk assessment tool. Investigation and clarification of risk and predisposing factors for DVT were identified from the literature, expert nursing knowledge, and medical staff input. Second, item development and weighting were undertaken. Third, parametric testing for content validity measured the differences in mean assessment tool scores between a group of patients who developed DVT in the hospital and a demographically similar group who did not develop DVT. Interrater reliability was measured by having three different nurses score each patient and compare the differences in scores among the three. FINDINGS: The DVT group had significantly higher scores on the JFK DVT assessment scale than did those who did not experience DVT. Interrater reliability showed a strong correlation among the scores of the three nurses (.98). DISCUSSION: Providing a valid and reliable tool for measuring the risk for DVT or PE in hospitalized patients will enable nurses to intervene early in patients at risk. Basing DVT risk assessment on the evidence provided in this study will assist nurses in becoming more confident in recognizing the necessity for interventions in hospitalized patients and decreasing risk. IMPLICATIONS: Nurses can now evaluate patients at risk for DVT or PE using the JFK Medial Center's risk assessment tool. PMID- 17355407 TI - Creating infrastructure supportive of evidence-based nursing practice: leadership strategies. AB - BACKGROUND: Nursing leadership is the cornerstone of successful evidence-based practice (EBP) programs within health care organizations. The key to success is a strategic approach to building an EBP infrastructure, with allocation of appropriate human and material resources. PURPOSE: This article indicates the organizational infrastructure that enables evidence-based nursing practice and strategies for leaders to enhance evidence-based practice using "the conceptual model for considering the determinants of diffusion, dissemination, and implementation of innovations in health service delivery and organization." DISCUSSION: Enabling EBP within organizations is important for promoting positive outcomes for nurses and patients. Fostering EBP is not a static or immediate outcome, but a long-term developmental process within organizations. Implementation requires multiple strategies to cultivate a culture of inquiry where nurses generate and answer important questions to guide practice. IMPLICATIONS: Organizations that can enable the culture and build infrastructure to help nurses develop EBP competencies will produce a professional environment that will result in both personal growth for their staff and improvements in quality that would not otherwise be possible. PMID- 17355408 TI - An exploration of the factor structure of the nursing work index. AB - RATIONALE: The nurse shortage is increasing in the developed world. Organisational context is important in determining issues associated with nurse shortages, such as retention, recruitment, and job satisfaction. Recent research has utilised the Nursing Work Index-Revised (NWI-R) as a measure of organisational context traits. Within the NWI-R a four-factor model has been reported as being important in determining good organisational context, yet researchers have recently questioned the stability of the four-factor structure. AIM: No known study has attempted to replicate the four-factor structure reported in the NWI-R. The aim of this research is to examine the factor structure of the 15 items that comprise the four factors of the NWI-R. METHODS: The NWI-R is an instrument that is focused on capturing organisational attributes that characterise professional nursing environments. A random sample of 172 (50%) acute care hospital nurses completed the NWI-R as part of a larger research project. The sample was diverse concerning nursing grade and specialty. Data were analysed using SPSS.11.0 to extract factors' structures (principal component and maximum likelihood), measures of homogeneity and descriptive statistics were generated from the findings. RESULTS: The four-factor structure of the NWI-R was not replicated in the data analysis. Instead a modified three-factor structure was identified accounting for 57% of the variance. Measures of internal consistency were acceptable. DISCUSSION: Previous research utilised the four factors of the NWI-R as a method to identify supportive organisational context and practice. The three-factor model raises questions regarding the stability of the findings using the NWI-R. This research shows the synthesis of the two models in light of previous findings. CONCLUSIONS/IMPLICATIONS: The findings might have far reaching implications for research that has utilised the NWI-R as a measure of organisational context. Further research is required to examine this study's findings and literature. PMID- 17355409 TI - Appraising and comparing pressure ulcer guidelines. AB - BACKGROUND: Whilst considerable activity has been related to guideline development for nurses regarding pressure ulcer prevention and management, no attempt has been made to comparatively evaluate these guidelines against some form of quality indicators. AIM: To compare and contrast four national pressure ulcer guidelines, and identify similarities and differences in their quality and content. METHODS: An international comparative appraisal method, using the AGREE (Appraisal of Guidelines Research and Evaluation) instrument, was undertaken to appraise four published pressure ulcer guidelines. Two further domains were added to the AGREE instrument to assess comparability of the guidelines and their perceived contribution to practice. An international group undertook the comparative appraisal. RESULTS: The domain scores for each guideline show some but not total agreement among reviewers. One particular set of guidelines was identified as scoring highest in a majority of AGREE domains. Overall, evidence of variability exists between pressure ulcer guidelines and common areas of development to consider for all guidelines. IMPLICATIONS FOR PRACTICE: The results raise many questions concerning the "best" pressure ulcer guideline to use, particularly related to the AGREE scoring. Some notable shortcomings exist in all the pressure ulcer guidelines reviewed and these shortcomings need to be addressed from a quality perspective. However, other issues such as style of reporting and potential contribution to practice might more fully affect choice by practitioners as opposed to guideline developers. CONCLUSIONS: Notable differences exist among the four guidelines that are possibly explained by different approaches to development and also because of different cultural factors and intentions for use. Whilst the AGREE tool identifies the quality of the guideline development process it still requires local engagement with practitioners to determine which guideline should be implemented. PMID- 17355410 TI - Implementing guidelines to improve medication safety for hospitalised patients: experiences from Western Health, Australia. PMID- 17355411 TI - Evaluation: an essential step to the EBP process. PMID- 17355413 TI - Detection of Celiac disease in primary care: a multicenter case-finding study in North America. AB - BACKGROUND: Celiac disease (CD) is one of the most common lifelong disorders in western countries. However, most cases remain currently undiagnosed in North America, mostly due to poor awareness of CD by primary care physicians. OBJECTIVES: The aims of this study were (a) to determine whether an active case finding strategy in primary care could increase the frequency of CD diagnosis and (b) to determine the most common clinical presentations of the condition. METHODS: This was a multicenter, prospective study involving adult subjects during the years 2002-2004, attending one of the participating practices. All individuals with symptoms or conditions known to be associated with CD were tested for immunoglobulin A anti-transglutaminase (tTG) antibodies, and those with elevated anti-tTG were subsequently tested for IgA antiendomysial antibodies (EMA). All subjects who were positive for EMA were advised to undergo an intestinal biopsy and HLA typing. RESULTS: The study group included 737 women and 239 men, with a median age of 54.3 yr. A positive anti-tTG test was found in 30 out of 976 investigated subjects (3.07%, 95% CI 1.98-4.16). CD was diagnosed in 22 patients (18 women, 4 men). The most frequent reasons for CD screening in these 22 cases were bloating (12/22), thyroid disease (11/22), irritable bowel syndrome (7/22), unexplained chronic diarrhea (6/22), chronic fatigue (5/22), and constipation (4/22). The prevalence of CD in the serologically screened sample was 2.25% (95% CI 1.32-3.18). The diagnostic rate was low at baseline (0.27 cases per thousand visits, 95% CI 0.13-0.41) and significantly increased to 11.6 per thousand visits (95% CI 6.8-16.4, P < 0.001) following active screening implementation. CONCLUSIONS: This study demonstrates that an active case-finding strategy in the primary care setting is an effective means to improve the diagnostic rate of CD in North America. PMID- 17355414 TI - Gastroduodenal injury after radioembolization of hepatic tumors. AB - BACKGROUND: Radioembolization is a new tool for the treatment of hepatic tumors that consists in the injection of biocompatible microspheres carrying radioisotopes into the hepatic artery or its branches. METHODS: We have performed radioembolization in 78 patients with hepatic tumors using resin-based microspheres loaded with yttrium-90. All patients were previously evaluated to minimize the risk of hazardous irradiation to nontarget organs and to obtain the data needed for dose calculation. RESULTS: We report a complication found in three cases (3.8%) that consists of abdominal pain resulting from gastroduodenal lesions and that had a chronic, insidious course. Microscopically, microspheres were detected in the specimens obtained from all affected gastric areas. Since these gastroduodenal lesions do not appear when nonradiating microspheres are injected in animals, lesions are likely to be due to radiation and not to an ischemic effect of vascular occlusion by spheres. CONCLUSIONS: We believe that a pretreatment evaluation that includes a more thorough scrutiny of the hepatic vascularization in search of small collaterals connecting to the gastroduodenal tract can help prevent this awkward complication. PMID- 17355415 TI - Vascular and cellular stress in inflammatory bowel disease: revisiting the role of homocysteine. AB - Moderate hyperhomocysteinemia is a complex trait commonly associated with inflammatory bowel disease (IBD). Nutritional deficiencies and genetic determinants have been identified as risk factors for moderate hyperhomocysteinemia, such as folate and vitamin B(12) deprivation and polymorphisms in the 5,10 methylenetetrahydrofolate reductase (MTHFR) encoding gene, respectively. Homocysteine has a crucial role in cellular stress, epigenetic events, inflammatory processes, and host-microbial interactions. Hyperhomocysteinemia might therefore influence the clinical history of IBD, including disease severity, susceptibility to particular enteric infections, and the risk for the development of colorectal cancer. In contrast, homocysteine metabolism does not seem to contribute to the greater risk of thrombosis in IBD subjects. Herein, we review the evidence linking homocysteine metabolism to the pathophysiology of IBD. Furthermore, we discuss the relevance of screening and treating folate and vitamin B(12) deficiencies in IBD subjects. Given the peculiar frequency of such deficiencies in IBD, normalizing vitamin levels should be an integral part of the management of these patients, especially those with active disease, history of intestinal resection, and/or treated with methotrexate. PMID- 17355416 TI - Risk for gastric cancer after cholecystectomy. AB - BACKGROUND: It is becoming increasingly evident that chronic inflammation may predispose cancer development. In the stomach, inflammation caused by Helicobacter pylori infection is linked to gastric cancer. Cholecystectomy is regularly followed by duodenogastric bile reflux and reactive gastritis. To test whether a noninfectious long-standing inflammation impels gastric carcinogenesis as well, we assessed the risk of gastric cancer in a large, population-based cohort of cholecystectomized patients. METHODS: We identified 251,672 individuals, in the Swedish National Inpatient Register, who had undergone cholecystectomy between 1970 and 1997. All incident cases of gastric cancer were identified through linkage to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for comparisons with cancer rates of the general population in Sweden. RESULTS: We found an 11% greater overall risk of distal gastric cancer (SIR=1.11, 95% CI 1.04-1.19). The risk increase was only observed among men (SIR=1.21, 95% CI 1.10-1.32), whereas no excess risk was evident for women. For men, the risk was elevated for up to 10 yr after surgery, but this elevation disappeared with longer follow-up time. There was no clear association between cholecystectomy and cardia cancer (SIR=0.95, 95% CI 0.76-1.16). CONCLUSIONS: Inconsistency over gender strata, implausibly short induction and latency time, and disappearance of the effect over time makes a causal relationship between cholecystectomy and distal gastric cancer less likely. The findings set aside concerns of harmful long-term consequences of cholecystectomy. PMID- 17355417 TI - Attitudes toward prenatal genetic testing in patients with familial adenomatous polyposis. AB - OBJECTIVES: Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome with >95% risk of colorectal cancer without prophylactic colectomy. Classic FAP is commonly associated with adenomatous polyposis coli (APC) gene mutations. If a mutation is identified, prenatal testing can reveal whether an embryo or fetus is affected. We conducted a pilot study to assess FAP patients' attitudes toward prenatal testing. METHODS: Twenty individuals with FAP completed a 40-item survey on personal and family history related to FAP, demographics, and attitudes toward prenatal tests including amniocentesis, chorionic villous sampling (CVS), and preimplantation genetic diagnosis (PGD). RESULTS: Thirteen women and seven men participated. Ninety-five percent (19/20) would consider undergoing prenatal testing for FAP: 90% would consider PGD, 75% would consider amniocentesis or CVS. Having an affected child and experiencing a first-degree relative's (FDR) death secondary to FAP were associated with greater willingness to consider prenatal testing. Personal history of cancer or FAP-associated tumors did not influence the decision to consider prenatal testing. One hundred percent said it was ethical to provide prenatal testing for FAP and four of five subjects who self-reported strong religious backgrounds would consider prenatal testing for FAP. Early reassurance of having an unaffected child was the most important advantage of PGD and avoiding pregnancy termination was important for 64% and 71% of women and men, respectively. CONCLUSIONS: Patients with FAP are willing to consider prenatal testing to prevent transmission of disease to their children. Physicians caring for FAP patients should discuss available prenatal diagnostic options with patients of childbearing age. PMID- 17355418 TI - Long-term risk of gastric cancer by subsite in operated and unoperated patients hospitalized for peptic ulcer. AB - OBJECTIVE: We aimed to investigate whether the elevated risk of gastric cancer among patients with gastric ulcer (GU) and the enigmatic low risk among patients with duodenal ulcer (DU) pertain to both cardia and noncardia cancer. We also studied the risks among operated patients while taking the disparate baseline risks into consideration. METHODS: Retrospective cohorts of 59,550 and 79,412 unoperated patients with DU and GU, respectively, plus 12,840 patients with partial gastric resection and 8,105 with vagotomy, recorded in the Swedish Inpatient Register since 1970, were followed from the first hospitalization (date of operation for the surgery cohort) until occurrence of any cancer, death, emigration, definitive surgery, or December 31, 2003. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) expressed relative risk (RR), compared to the age-, sex-, and calendar period-matched Swedish population. Cox regression produced adjusted RR estimates among operated patients, relative to unoperated ones with the same ulcer type. RESULTS: While unoperated DU patients had a halved risk of noncardia cancer (SIR=0.5, 95% CI 0.4-0.7), their risk of cardia cancer was slightly above expectation (SIR=1.2, 95% CI 0.8-1.7). Unoperated GU patients had doubled risks for both cancers (SIR=2.1, 95% CI 2.0 2.4 and SIR=1.9, 95% CI 1.4-2.3, respectively). DU patients who underwent gastric resection had a 60% risk elevation (RR=1.6, 95% CI 1.0-2.5) compared to unoperated ones. Vagotomy was associated with a greater risk in the first 10 yr, but this excess disappeared with further follow-up. Resected GU patients had a 40% risk reduction relative to their unoperated peers (RR=0.6, 95% CI 0.5-0.8). This reduction persisted well beyond the first postoperative decade. CONCLUSION: The DU-related protection against gastric cancer does not seem to pertain to cardia cancer. With gastric resection, risks are shifted toward normality, regardless of underlying ulcer type. PMID- 17355419 TI - Time trends of ulcer mortality in non-European countries. AB - AIMS: The aim of the present study was to follow the time trends of mortality from gastric and duodenal ulcer in countries outside Europe and compare them with previous reports of ulcer mortality from Europe and North America. METHODS: Mortality data from eight different countries were analyzed, including Argentina, Australia, Chile, Hong Kong, Japan, Mexico, Singapore, and Taiwan. The age standardized death rates of individual countries were followed from 1971 to 2004. Japan and Australia had mortality data for more than 50 yr that provided the opportunity to conduct a birth-cohort analysis. RESULTS: The data from all countries were characterized by a decline in gastric and duodenal ulcer mortality. Except for Hong Kong, mortality from gastric ulcer was higher than mortality from duodenal ulcer. In Japan and Australia, mortality from gastric and duodenal ulcer displayed time trends that were consistent with an underlying birth-cohort phenomenon. The risk of dying from gastric and duodenal ulcer increased in consecutive generations born between the mid- and the end of the nineteenth century and decreased in all subsequent generations. The peak mortality from gastric ulcer occurred among generations born in 1875, whereas peak mortality from duodenal ulcer occurred among generations born 10-20 yr later. CONCLUSIONS: The ubiquitous decline in ulcer mortality in countries from different parts of the world is likely to be associated with a worldwide decline in the occurrence of H. pylori infection. The events accompanying the receding infection in developed countries must have similarly affected populations exposed to increasing standards of hygiene. PMID- 17355420 TI - Evidence-based veterinary dermatology: a systematic review of interventions for treatment of Pseudomonas otitis in dogs. AB - The efficacy and safety of pharmacological interventions to treat canine Pseudomonas otitis externa and media were evaluated based on the systematic review of clinical trials published between 1967 and 2006. Clinical trials were included if Pseudomonas species were cultured from the ears of dogs with otitis externa or otitis media prior to treatment, and if the outcome of these interventions was reported at the end of the study. Studies were compared with regard to design characteristics (randomization generation and concealment, masking, intention-to-treat analyses), benefit (microbiological and/or clinical resolution of the Pseudomonas otitis), and adverse effects. Ten trials reporting data on 162 patients and 13 different pharmacological interventions were identified. Based on the accepted criteria for quality of evidence, there is insufficient evidence for or against recommending the use of any of these treatments for Pseudomonas otitis in dogs. This is largely because there is only one trial supporting the use of each treatment option and none were randomized controlled trials. Future studies need to be prospective, randomized, blinded and controlled; designed to evaluate pharmacological interventions for otitis regardless of the infective organism; have appropriate statistical advice on recruitment numbers, the power of the study and appropriate statistical analysis; include details of underlying conditions and concomitant treatments; and be designed such that inclusion criteria include microbial culture and antimicrobial sensitivity, and outcome assessments include clinical examination, cytology and microbial culture. PMID- 17355421 TI - Validation of CADESI-03, a severity scale for clinical trials enrolling dogs with atopic dermatitis. AB - In dogs, atopic dermatitis (AD) is a common and chronic allergic skin disease that often necessitates treatment with pharmacological interventions. In the last 30 years, numerous clinical trials testing the efficacy of anti-inflammatory drugs have been reported, but there has been a lack of consistency in the assessment of outcome measures. Several clinical scales have been employed over time, but none of these scoring systems were ever tested for validity and reliability. A committee of the International Task Force on Canine Atopic Dermatitis evaluated the currently available scales used to assess disease morbidity in humans and dogs with AD, and a third version of the Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) was designed. This version was expanded from previous ones by redistribution and increase in body sites tested, the use of an additional lesion reflecting underlying pruritus (e.g. self-induced alopecia) and an increase in the numerical range of severity for each lesion. The CADESI-03 scale was tested for validity and reliability in a cohort of 38 dogs with AD. Overall, this revised version of the CADESI was found to exhibit acceptable content, construct, criterion, and inter- and intra-observer reliability and sensitivity to change. As a result, this scale is recommended as a validated tool for assessment of disease severity in clinical trials testing the efficacy of interventions in dogs with AD. PMID- 17355422 TI - Intradermal injection of heat-killed Mycobacterium vaccae in dogs with atopic dermatitis: a multicentre pilot study. AB - Canine atopic dermatitis (cAD) is a common disease with a multifactorial aetiology associated with impaired immunoregulation. The immunopathogenesis has similarities to that of human atopic dermatitis. Clinical signs of allergic disease in humans and mice are reduced by administration of saprophytic mycobacteria that amplify regulatory cytokines and hence the effect of Mycobacterium vaccae on the clinical severity of cAD was investigated. Sixty-two dogs with cAD, selected according to strict criteria, were treated with a single intradermal injection and evaluated monthly for 3 months in a placebo-controlled double-blind clinical trial. Clinical severity was quantified using standardized scores and by owner assessment of pruritus. A single injection of a heat-killed suspension of M. vaccae was found to be well tolerated and effective in treating mild to moderate cases of cAD demonstrable for 3 months, but was insignificant in more severely affected dogs. PMID- 17355423 TI - Pilot study: prevalence of positive aeroallergen reactions in 10 cats with small airway disease without concurrent skin disease. AB - The purpose of this study was to determine the prevalence of positive allergen reactions in cats with small-airway disease (i.e. 'feline asthma', 'feline allergic bronchitis', 'feline bronchial disease'). Intradermal skin tests (IDT) and serum immunoglobulin E (IgE) tests were performed in 10 cats with idiopathic small-airway disease and in 10 normal cats without a history of respiratory disease. None of the cats had a history of skin disease or clinical signs of skin disease at the time of testing. Significantly more individual positive allergen reactions were found on serum IgE tests than on IDT in both groups of cats. Affected cats had significantly more individual positive allergen reactions on both tests than unaffected cats. Both IDT and serum IgE tests resulted in more individual positive allergen reactions to weeds, trees, grasses, and/or moulds in affected cats than in normal cats. Significantly more positive allergen reactions to house dust mites were found in affected compared to non-affected cats by IDT but not by serum IgE testing. One unexpected obstacle to inclusion of more affected cats in the study was the concurrent presence or history of suspect or known allergic skin disease. Concurrent allergic skin disease has not been reported in association with small-airway disease in cats. The increased prevalence of individual positive allergen reactions in affected cats may be due to increased immunological reactivity in these cats. Further studies are needed to answer this question and to determine what role, if any, aeroallergens have in the pathogenesis of this complex feline disease. PMID- 17355424 TI - Investigation on the association between atopic dermatitis and the development of mycosis fungoides in dogs: a retrospective case-control study. AB - In human medicine, the relationship between the immunodysregulation observed in atopic dermatitis (AD) and the development of mycosis fungoides (MF) has triggered considerable interest due to the increasing number of patients with MF who have a previous history of AD. The purpose of this retrospective case-control study was to investigate whether dogs diagnosed with MF were more likely to have AD. The records of 96 000 canine patients at the University of Florida were searched. Inclusion criteria were a clinical and histological diagnosis of MF. Dogs admitted to the University of Florida, Veterinary Medical Center during the same time period (1991-2004) without a diagnosis of MF were included as controls. Four controls for each study dog were randomly selected (matched by year of admission). Frequency of AD and other exposure variables were compared among case and control dogs by using conditional logistic regression. Records of 19 dogs with a diagnosis of MF were identified. Five of them (5/19, 26.3%) had previous diagnosis of AD. The odds of having MF was 12 times (OR = 12.54; 95% CI = 1.95 80.39; P < 0.01) higher in dogs with AD than in dogs without AD. In conclusion, this study suggests an association between AD and MF in dogs. Future studies are necessary to confirm this finding and to investigate the pathogenic mechanisms involved in this association. PMID- 17355425 TI - Effects of cyclosporin A and cilomilast on activated canine, murine and human keratinocytes. AB - The calcineurin inhibitor cyclosporin A and the phosphodiesterase 4 inhibitor cilomilast exhibit potent immunomodulatory properties which make them interesting therapeutics for the treatment of skin disorders like canine and human atopic dermatitis. Cyclosporin A and phosphodiesterase 4 inhibitors have already demonstrated clinical efficacy in the therapy of canine and human atopic dermatitis. Their direct impact on keratinocytes, especially canine keratinocytes, is less obvious. Thus, an investigation was carried out to ascertain whether cyclosporin A and cilomilast modulate keratinocyte proliferation and secretion of proinflammatory mediators. Cyclosporin A inhibited canine and murine keratinocyte proliferation, whereas cilomilast had no affect. Cyclosporin A and cilomilast reduced the lipopolysaccharide-induced prostaglandin E2 synthesis in canine and murine keratinocytes. Both immunomodulators also inhibited the production of the CXC chemokine KC and CCL2 in the murine keratinocyte cell line MSC-P5. The two immunomodulators also significantly reduced the interferon-gamma-induced production of interferon-gamma-inducible protein 10 in human keratinocytes (HaCaT cells). Thus, cyclosporin A and cilomilast directly modulate keratinocyte functions which might contribute to the anti-inflammatory and immunomodulatory action of these compounds in the treatment of allergic skin diseases. PMID- 17355426 TI - In vitro activity of an ear rinse containing tromethamine, EDTA, benzyl alcohol and 0.1% ketoconazole on Malassezia organisms from dogs with otitis externa. AB - The purpose of this study was to evaluate the in vitro activity of an ear rinse containing tromethamine, EDTA, benzyl alcohol and 0.1% ketoconazole in purified water on Malassezia organisms from dogs with otitis externa. Malassezia organisms were collected from ear swab samples from the external ear canal of 19 dogs with otitis externa plus one control strain of Malassezia pachydermatis. Three test solutions were evaluated: ER (EDTA, tromethamine, benzyl alcohol), ER + keto (EDTA, tromethamine, benzyl alcohol, ketoconazole), and H2O (purified water). Ten millilitre aliquots of each test solution was transferred into 20 tubes and inoculated with one of the isolates (1 tube per isolate: 19 clinical and 1 control strain). Samples were retrieved from each tube at five time points (0, 15, 30, 45 and 60 min), transferred to Petri dishes, mixed with Sabouraud dextrose agar supplemented with 0.5% Tween 80 and incubated. Following incubation, the plates were examined for growth and colonies counted as colony forming units per millilitre. The data were analysed using a repeated measures analysis, with pair-wise comparisons of solution-time combinations. There was a significant reduction in Malassezia growth in ER + keto at all time points (P < 0.0001) compared to time zero. Neither ER nor H2O had any effect on the growth of Malassezia. ER + keto was significantly more effective in reducing Malassezia growth (P < 0.0001) at all time points compared to both ER and H2O. ER + keto may be useful in the treatment of Malassezia otitis externa. Future studies should be performed to evaluate the in vivo efficacy of ER + keto as treatment for otic infections caused by Malassezia. PMID- 17355427 TI - Variability of laboratory identification and antibiotic susceptibility reporting of Pseudomonas spp. isolates from dogs with chronic otitis externa. AB - The purpose of this study was to evaluate interlaboratory variation in isolation and antibiotic susceptibility pattern of Pseudomonas spp. as reported to veterinarians for cases of canine chronic bacterial otitis externa. Twenty-six dogs with unilateral or bilateral bacterial otitis externa from multiple referral practices were included in this prospective study. Triplicate samples collected simultaneously from the same location in the external ear canal were randomly submitted to three laboratories for culture and susceptibility testing. Pseudomonas spp. were isolated from 18 of 34 (53%) ears. All three laboratories agreed on the presence of Pseudomonas spp. in 15 (83.3%) ears sampled. However, two laboratories agreed on two (11.1%) occasions, and on one occasion (5.5%) Pseudomonas spp. were identified in only one laboratory. Minimum inhibitory concentration (MIC) susceptibilities to 11 antibiotics were compared between laboratories B and C. Using laboratory-defined susceptibility of sensitive (S), intermediate (I) and resistant (R), none of the 16 Pseudomonas spp. with MIC data reported had identical patterns of antibiotic susceptibility. Agreement in susceptibility to individual antibiotics was observed in 13 of 16 (81%) occasions for amikacin and gentamicin, 10 of 16 (63%) occasions for ticarcillin, and nine of 16 (56%) for enrofloxacin. These results indicate that Pseudomonas spp. were identified by all three laboratories chosen for this study in 83% of the time. Moreover, antibiotic susceptibility patterns and MIC values reported to veterinarians may not agree between laboratories. Veterinarians should interpret bacterial culture and susceptibility results with multiple caveats including variability between laboratories. PMID- 17355428 TI - Canine notoedric mange: a case report. AB - Notoedric mange is a cutaneous ectoparasitic disease of cats caused by Notoedres cati, a mite belonging to the Sarcoptidae family. The disease occurs in felids, occasionally in other mammals and in humans. The canine form, even if cited by some authors, has never been documented. This report describes for the first time a case of notoedric mange in a dog. PMID- 17355429 TI - Congenital lipoblastoma in a neonate calf: first report in veterinary literature. AB - Lipoblastoma is a rare benign tumour of adipose tissue that usually occurs in young children. Although around 100 cases of lipoblastoma have been reported in humans, no report has been previously described in animals. This case report describes the clinical and histopathological findings of a congenital lipoblastoma located at the tail base of a 2-day-old male calf. Grossly, the mass was pink with a partly ulcerated and haemorrhagic surface. The calf showed no neurological deficits. Radiographs of the vertebral column revealed no abnormalities, and surgical excision was performed. Histopathology of the mass was consistent with lipoblastoma. The calf was followed up for 13 months and found to be healthy with no signs of recurrence. To the best of the authors' knowledge, this is the first case of lipoblastoma in the veterinary literature. Lipoblastoma should thus be considered in the differential diagnosis list for congenital adipose tissue tumours in animals. PMID- 17355430 TI - A case of multiple epitrichial sweat gland ductal carcinomas in a horse. AB - This case report describes a rare epitrichial sweat gland ductal carcinoma in a 14-year-old horse and is the first report of multiple carcinomas of this type in horses. Although several tumours developed, mostly on the distal extremities, over a 2-year period, the horse remained otherwise healthy. Topical treatment with imiquimod was successful for many of them. PMID- 17355431 TI - Relative sensitivity of hair pluckings and exudate microscopy for the diagnosis of canine demodicosis. AB - This study was designed to compare the sensitivity of deep skin scraping, hair plucking, and exudate microscopy for the diagnosis of canine demodicosis. Sixty seven dogs diagnosed with demodicosis were enrolled in the study. Thirty dogs had localized and 37 had generalized demodicosis. Twenty-seven of the 67 dogs had complicated (secondarily infected) and 40 had noncomplicated form. On each dog, a single lesion was randomly selected to obtain one deep skin scraping, hair plucking, and, when present (n = 13) exudate. For skin scraping and exudate microscopy, an area under a cover slip measuring 2.2 x 2.2 mm was examined, while trichography included the evaluation of 100 hair shafts. At least one parasitic element was found in 85.1% of trichograms, and 100% of exudate preparations. The number of parasitic elements was higher in skin scrapings compared to the other two methods. The diagnostic sensitivity of skin scrapings was higher than that of hair pluckings for the total number of samples (P = 0.002) and for those obtained from dogs with the localized (P = 0.004) and the noncomplicated (P = 0.002) forms of the disease. The diagnostic sensitivity of hair pluckings was higher in generalized and complicated demodicosis compared to the localized and noncomplicated variants. Based on these results, exudate microscopy may be equally sensitive to deep skin scrapings, and trichography may be of value in generalized and complicated demodicosis, although a negative result cannot rule it out. PMID- 17355433 TI - A mutation in NLA, which encodes a RING-type ubiquitin ligase, disrupts the adaptability of Arabidopsis to nitrogen limitation. AB - Abundant nitrogen is required for the optimal growth and development of plants, while numerous biotic and abiotic factors that consume soil nitrogen frequently create a nitrogen limitation growth condition. To cope with this, plants have evolved a suite of adaptive responses to nitrogen limitation. However, the molecular mechanism governing the adaptability of plants to nitrogen limitation is totally unknown because no reported mutant defines this trait. Here we isolated an Arabidopsis mutant, nla (nitrogen limitation adaptation), and identified the NLA gene as an essential component in this molecular mechanism. Supplied with insufficient inorganic nitrogen (nitrate or ammonium), the nla mutant failed to develop the essential adaptive responses to nitrogen limitation, but senesced much earlier and more rapidly than did the wild type. Under other stress conditions including low phosphorus nutrient, drought and high temperature, the nla mutant did not show this early senescence phenotype, but closely resembled the wild type in growth and development. Map-based cloning of NLA revealed that this gene encodes a RING-type ubiquitin ligase, and nla is a deletion mutation which does not code for the RING domain in the NLA protein. The NLA protein is localized to the nuclear speckles, where this protein interacts with the Arabidopsis ubiquitin conjugase 8 (AtUBC8). In the nla mutant, the deletion of the RING domain from NLA altered its subcellular localization, disrupted the interaction between NLA and AtUBC8 and caused the early senescence phenotype induced by low inorganic nitrogen. All the results indicate that NLA is a positive regulator for the development of the adaptability of Arabidopsis to nitrogen limitation. PMID- 17355434 TI - Limitation of nocturnal import of ATP into Arabidopsis chloroplasts leads to photooxidative damage. AB - When grown in short day conditions and at low light, leaves of Arabidopsis plants with mutations in the genes encoding two plastidial ATP/ADP transporters (so called null mutants) spontaneously develop necrotic lesions. Under these conditions, the mutants also display light-induced accumulation of H(2)O(2) and constitutive expression of genes for copper/zinc superoxide dismutase 2 and ascorbate peroxidase 1. In the light phase, null mutants accumulate high levels of phototoxic protoporphyrin IX but have only slightly reduced levels of Mg protoporphyrin IX. The physiological changes are associated with reduced magnesium-chelatase activity. Since the expression of genes encoding any of the three subunits of magnesium-chelatase is similar in wild type and null mutants, decreased enzyme activity is probably due to post-translational modification which might be due to limited availability of ATP in plastids during the night. Surprisingly, the formation of necrotic lesions was absent when null mutants were grown either in long days and low light intensity or in short days and high light intensity. We ascribe the lack of lesion phenotype to increased nocturnal ATP supply due to glycolytic degradation of starch which may lead to additional substrate-level phosphorylation in the stroma. Thus, nocturnal import of ATP into chloroplasts represents a crucial, previously unknown process that is required for controlled chlorophyll biosynthesis and for preventing photooxidative damage. PMID- 17355435 TI - Identification and functional characterization of cation-chloride cotransporters in plants. AB - Chloride (Cl(-)) is an essential nutrient and one of the most abundant inorganic anions in plant tissues. We have cloned an Arabidopsis thaliana cDNA encoding for a member of the cation-Cl(-) cotransporter (CCC) family. Deduced plant CCC proteins are highly conserved, and phylogenetic analyses revealed their relationships to the sub-family of animal K(+):Cl(-) cotransporters. In Xenopus laevis oocytes, the A. thaliana CCC protein (At CCC) catalysed the co-ordinated symport of K(+), Na(+) and Cl(-), and this transport activity was inhibited by the 'loop' diuretic bumetanide, a specific inhibitor of vertebrate Na(+):K(+):Cl( ) cotransporters, indicating that At CCC encodes for a bona fide Na(+):K(+):Cl(-) cotransporter. Analysis of At CCC promoter-beta-glucuronidase transgenic Arabidopsis plants revealed preferential expression in the root and shoot vasculature at the xylem/symplast boundary, root tips, trichomes, leaf hydathodes, leaf stipules and anthers. Plants homozygous for two independent T DNA insertions in the CCC gene exhibited shorter organs such as inflorescence stems, roots, leaves and siliques. The elongation zone of the inflorescence stem of ccc plants often necrosed during bolt emergence, while seed production was strongly impaired. In addition, ccc plants exhibited defective Cl(-) homeostasis under high salinity, as they accumulated higher and lower Cl(-) amounts in shoots and roots, respectively, than the treated wild type, suggesting At CCC involvement in long-distance Cl(-) transport. Compelling evidence is provided on the occurrence of cation-chloride cotransporters in the plant kingdom and their significant role in major plant developmental processes and Cl(-) homeostasis. PMID- 17355436 TI - The chloroplast HSP70B-CDJ2-CGE1 chaperones catalyse assembly and disassembly of VIPP1 oligomers in Chlamydomonas. AB - The vesicle-inducing protein in plastids (VIPP1) is essential for the biogenesis of thylakoid membranes in cyanobacteria and plants. VIPP1 and its bacterial ancestor PspA form large homo-oligomeric rings of >1 MDa. We recently demonstrated that VIPP1 interacts with the chloroplast J-domain co-chaperone CDJ2 and its chaperone partner HSP70B, and hypothesized that the chaperones might be involved in the assembly and/or disassembly of VIPP1 oligomers. To test this hypothesis, we analysed the composition of VIPP1/chaperone complexes in Chlamydomonas reinhardtii cell extracts and monitored effects of the chaperones on VIPP1 assembly states in vitro. We found that CGE1, the chloroplast GrpE homologue, is also part of complexes with HSP70B, CDJ2 and VIPP1. We observed that CDJ2-VIPP1 accumulated as low- and high-molecular-weight complexes in ATP depleted cell extracts, but as intermediate-size complexes in extracts supplemented with ATP. This was consistent with a role for the chaperones in VIPP1 assembly and disassembly. Using purified proteins, we could demonstrate that the chaperones indeed facilitated both the assembly and disassembly of VIPP1 oligomers. Electron microscopy studies revealed that, in contrast to PspA, VIPP1 rings assembled into rod-shaped supercomplexes that were morphologically similar to microtubule-like structures observed earlier in various plastid types. VIPP1 rods, too, were disassembled by the chaperones, and chaperone-mediated rod disassembly also occurred when VIPP1 lacked an approximately 30-aa C-terminal extension present in VIPP1 homologues but absent in PspA. By regulating the assembly state of VIPP1, the chloroplast HSP70 chaperone system may play an important role in the maintenance/biogenesis of thylakoid membranes. PMID- 17355437 TI - Infection of tobacco with different Pseudomonas syringae pathovars leads to distinct morphotypes of programmed cell death. AB - Tobacco plants (Nicotiana tabacum cv. Xanthi-nc) infiltrated with either of two pathovars of Pseudomonas syringae- an avirulent strain of P. syringae pv. tabaci (Pst) or the non-host pathogen P. syringae pv. maculicola M2 (Psm) - developed a hypersensitive response (HR). There were considerable differences in HR phenotype, timing and sequence of cell dismantling between the two pathosystems. Following Psm infiltration, the first macroscopic signs were visible at 4.5 h post-infiltration (hpi). Simultaneously, increased plasma membrane permeability was observed, suggesting that the loss of cell membrane integrity initiates the macroscopic HR evoked by Psm. In contrast, after Pst treatment there was a distinct time lapse between the first signs of tissue collapse (9 hpi) and the occurrence of plasma membrane discontinuity (12 hpi). Ultrastructural studies of cells undergoing the HR triggered by Psm and Pst revealed distinct patterns of alterations in morphology of organelles. Moreover, while different forms of nuclear degeneration were observed in leaf zones infiltrated with Pst, we failed to detect any abnormalities in the nuclei of Psm-treated tissue. In addition, application of synthetic caspase inhibitors (Ac-DEVD-CHO, Ac-YVAD-CMK) abolished HR induced by Pst, but not Psm. Our observations suggest that different cell death mechanisms are executed in response to Psm and Pst. Interestingly, pre inoculation with Pst, but not with Psm, induced a long-distance acquired resistance (LDAR) response, even though locally a typical set of defense responses, including acquired resistance, was activated locally in response to Psm. The failure of Psm to induce LDAR may be due to the rapid degeneration of bundle sheath cells resulting from Psm infection. PMID- 17355438 TI - The ABC transporter AtPDR8 is a cadmium extrusion pump conferring heavy metal resistance. AB - Cadmium (Cd) and lead (Pb) are widespread pollutants that are toxic to plant growth. The expression of AtPDR8 was upregulated in cadmium- or lead-treated Arabidopsis thaliana. To test whether AtPDR8 is involved in heavy metal resistance, we examined transgenic Arabidopsis that over-expressed AtPDR8 and RNAi plants that exhibited a severely reduced AtPDR8 transcript level, as well as T-DNA insertion mutants of this ABC transporter. AtPDR8-over-expressing plants were more resistant to Cd(2+) or Pb(2+) than the wild-type and had lower Cd contents. In contrast, AtPDR8 RNAi transgenic plants and T-DNA insertion lines were more sensitive to Cd(2+) or Pb(2+) compared to wild-type plants and had higher Cd contents. The GFP-AtPDR8 protein was targeted to the plasma membrane, and GUS activity was present in most cells but strongest in the root hair and epidermal cells. Cd extrusion was higher in the AtPDR8-over-expressing plants in a flux assay using isolated protoplasts and radioactive (109)Cd, and was lower in the RNAi transgenic plants than in the wild-type. Together, these data strongly support a role for AtPDR8 as an efflux pump of Cd(2+) or Cd conjugates at the plasma membrane of Arabidopsis cells. As AtPDR8 has been suggested to be involved in the pathogen response and in the transport of chemicals that mediate pathogen resistance, this ABC protein is likely to transport a very broad range of substrates. PMID- 17355439 TI - Estimation of metabolic fluxes, expression levels and metabolite dynamics of a secondary metabolic pathway in potato using label pulse-feeding experiments combined with kinetic network modelling and simulation. AB - In this paper we present a method that allows dynamic flux analysis without a priori kinetic knowledge. This method was developed and validated using the pulse feeding experimental data obtained in our previous study (Matsuda et al., 2005), in which incorporation of exogenously applied l-phenylalanine-d(5) into seven phenylpropanoid metabolites in potato tubers was determined. After identification of the topology of the metabolic network of these biosynthetic pathways, the system was described by dynamic mass balances in combination with power-law kinetics. After the first simulations, some reactions were removed from the network because they were not contributing significantly to network behaviour. As a next step, the exponents of the power-law kinetics were identified and then kept at fixed values during further analysis. The model was tested for statistical reliability using Monte Carlo simulations. Most fluxes could be identified with high accuracy. The two test cases, control and after elicitation, were clearly distinguished, and with elicitation fluxes to N-p coumaroyloctopamine (pCO) and N-p-coumaroyltyramine (pCT) increased significantly, whereas those for chlorogenic acid (CGA) and p-coumaroylshikimate decreased significantly. According to the model, increases in the first two fluxes were caused by induction/derepression mechanisms. The decreases in the latter two fluxes were caused by decreased concentrations of their substrates, which in turn were caused by increased activity of the pCO- and pCT-producing enzymes. Flux-control analysis showed that, in most cases, flux control was changed after application of elicitor. Thus the results revealed potential targets for improving actions against tissue wounding and pathogen attack. PMID- 17355440 TI - How much do pregnant women need to eat - should we intervene? PMID- 17355441 TI - Nutritional status in pregnant adolescents: a systematic review of biochemical markers. AB - Adolescent pregnancy is a major public health challenge for many industrialized countries and is associated with significant medical, nutritional, social and economic risk for mothers and their infants. Despite this, relatively little is known about the nutritional status of this population. The aim of this paper was to conduct a systematic review of the current evidence relating to the biochemical markers of nutritional status of pregnant adolescents living in industrialized countries. Six papers were identified that fulfilled the inclusion criteria, the majority of which were conducted in the United States. The studies were of variable quality and most failed to control for potential confounders which may have strongly influenced the findings. Due to limited research, conclusions cannot be drawn about the zinc and calcium status of pregnant adolescents, and data on folate and vitamin B(12) status appeared conflicting. There was some consensus among studies, however, to suggest that indicators of anaemia and iron status were compromised in pregnant adolescents, particularly during the third trimester of pregnancy. Chronological age did not appear to influence nutritional status, although there was some evidence to suggest that increasing gynaecologic age may positively influence plasma ferritin levels. Current research is limited by sampling and measurement bias, and research is urgently required to address these limitations. Further consideration should also be made of the influence of the role of socio-economic support on pregnant adolescents' nutritional status. The achievement of improved nutrition in pregnancy among adolescents requires multidisciplinary collaborations of adolescent healthcare providers, academics, professional organizations, policymakers, industry and service users. Only once this is achieved can adolescent nutrition, and adolescent nutrition in pregnancy, be significantly and sustainably optimized. PMID- 17355442 TI - Maternal depression and infant growth: a review of recent evidence. AB - Depressive disorder occurring during pregnancy and the post-natal period (maternal depression) is common in both developed and developing countries. It can cause functional impairment at a time when the mother is performing tasks vital to her infant's growth and development. This article reviews recent research investigating whether there is an association between maternal depression and infant growth impairment. A search was made using Medline for articles published in the last 10 years, and the results were scrutinized for relevance and quality. Eight studies from developing countries, and three from the UK, are described. Cohort studies from both India and Pakistan provide evidence that maternal depression is an independent risk factor for poor infant growth. However, studies from other developing countries are limited and conflicting in their findings. The UK-based research suggests that such an association occurs in mothers/infants living in conditions of socio-economic deprivation. This review discusses the potential mechanisms by which the relationship between maternal depression and infant growth outcomes may be explained: the effect of infant growth 'failure' upon maternal mood; the impact of maternal depression upon health-seeking behaviours, breastfeeding and mother child interaction; the relationship between antenatal depression and low infant birthweight; and economic, socio-cultural and confounding factors that may explain the variation between results from different settings. PMID- 17355443 TI - The 'Earlybird' gets the breastmilk: findings from an evaluation of combined professional and peer support groups to improve breastfeeding duration in the first eight weeks after birth. AB - Australia has high initiation rates of breastfeeding, but the challenges of establishing and maintaining breastfeeding in the first few months of infant life result in many women changing to artificial formula feeding. This paper reports on the impact of a new strategy to improve breastfeeding duration rates in the first 8 weeks post-partum. The Earlybird Program (EBP) combines the professional expertise of child and family health (C&FH) nurses with the expertise of the participating mothers to support each other in establishing breastfeeding in the first 8 weeks. This retrospective study compared the breastfeeding patterns of first-time mothers who attended the EBP, with the breastfeeding patterns of mothers who accessed individual appointments with the nurses in a 12-month period, and examined the predictors of continued breastfeeding at 8 weeks. The total sample comprised 193 infant records. Women who selected the EBP were more likely to be employed and less likely to be categorized as non-English speaking background. These women also had more visits to the C&FH service. Logistic regression was used to determine the factors associated with breastfeeding cessation at 8 weeks post-natal. After adjusting for variables, only exclusive breastfeeding at first visit and attending the EBP were significant predictors of continuing to breastfeed at 8 weeks. Facilitation skills that recognize the expertise of participating women were considered an important aspect of the programme. PMID- 17355444 TI - A survey of neonatal nutrition policies and practices in the UK and Eire. AB - Optimal nutrition is one of the fundamental components for infants to reach their full growth and neurodevelopmental potential. Best practice is facilitated by a contemporaneous, multidisciplinary, evidence-based nutrition policy. Such evidence has recently been reviewed. We have assessed: the prevalence of nutrition policies in neonatal units in the UK and Eire; their application to hypothetical cases; the availability of dietetic input; and whether any differences existed between non-regional and regional units. A standardized questionnaire was devised by a multidisciplinary group and posted to all 255 neonatal units in the UK and Eire in 2002. Replies from 67 neonatal units were received: 48 out of 233 non-regional and 19 out of 22 regional units. A feeding policy was present in 33 units, and regular access to dietitians occurred in 37 units. For a hypothetical infant less than 28 weeks' gestation, enteral feeds would be commenced at 0-2 days in 81% of non-regional and 94% of regional units (P = ns), and be continuous in 11% of non-regional and 32% of regional units, and bolus feeding in 89% of non-regional and 68% of regional units (P = ns). Routine fortification of breastmilk would occur more frequently in non-regional units (96%) than in regional units (79%) (P = 0.050). Vitamin and iron supplements would be given to infants receiving postdischarge or high-energy milks in 68% of non-regional units and in 79% of regional units (P = ns). Calorie counts (63% regional vs. 8% non-regional, P < 0.001), and daily weights (68% regional vs. 33% non-regional, P = 0.014), were used more frequently in regional units. Many units surveyed did not have a nutrition policy. Many infants receive unnecessary additional vitamins and supplements. Practice is variable throughout the country, but we found no evidence of major differences between regional and non-regional units, apart from their monitoring of growth and rates of breastmilk fortifier usage. PMID- 17355445 TI - Individual, household, programme and community effects on childhood malnutrition in rural India. AB - The children living in rural areas of India disproportionately suffer from malnutrition compared with their urban counterparts. The present article analyses the individual, household, community and programme factors on nutritional status of children in rural India. Additionally, we consider the random variances at village and state levels after introducing various observed individual-, household- and programme-level characteristics in the model. A multilevel model is conducted using data from the National Family and Health Survey 2. The results show that maternal characteristics, such as socio-economic and behavioural factors, are more influential in determining childhood nutritional status than the prevalence of programme factors. Also, it was found that individual factors show evidence of state- and village-level clustering of malnutrition. PMID- 17355446 TI - Overweight and obesity among affluent Bengalee schoolgirls of Lake Town, Kolkata, India. AB - A cross-sectional study was undertaken to determine the prevalence of overweight and obesity among 431 Bengalee schoolgirls aged 6-9 years in Kolkata, India. Anthropometric measurements of height and weight were made on 431 girls. The body mass index (BMI) was computed following the standard equation. Overweight and obesity was defined following the internationally accepted BMI cut-off points. Results revealed that the overall rates of overweight and obesity were 17.63% and 5.10%, respectively. A steady increase in number of overweight individuals was observed from 6 to 9 years. The prevalence of overweight among affluent Bengalee children was higher than those reported from other Asian countries. PMID- 17355449 TI - Hepatitis viruses: live and let die. AB - Viral hepatitis is a diffuse inflammatory reaction of the liver caused by hepatotropic viruses. Among the hepatitis viruses, only hepatitis B virus and hepatitis C virus are able to persist in the host and cause chronic hepatitis. In the course of persistent infection, inflammation forms the pathogenetic basis of chronic hepatitis that can lead to nodular fibrosis, which can progress to cirrhosis and, eventually, hepatocellular carcinoma (HCC). Of the different antiviral defense systems employed by the host, apoptosis significantly contributes to the prevention of viral replication, dissemination, and persistence. Pathomorphologic studies have shown acidophilic bodies and hepatocyte dropout, features that are compatible with apoptosis. The number of hepatocytes showing features of apoptosis in patients with chronic hepatitis B and C was found to be higher than in healthy subjects, indicating that apoptosis is involved in the pathogenesis of these diseases. There are various data suggesting that hepatitis B and C viral proteins may modulate apoptosis. Vice versa, mechanisms of apoptosis inhibition might represent central survival strategies employed by the virus which, in the end, may contribute to HCC development. While the expression and retention of viral proteins in hepatocytes may influence the severity and progression of liver disease, the mechanisms of liver injury in viral hepatitis are defined to be due not only to the direct cytopathic effects of viruses, but also to the host immune response to viral proteins expressed by infected hepatocytes. However, the exact role of these observations in relation to pathogenesis remains to be established. The mechanism and systems are complex. This report aims to provide an overview and intends to cite only a small number of pertinent references. PMID- 17355450 TI - Therapeutic management of recurrent hepatitis C after liver transplantation. AB - Recurrent hepatitis C ranges from minimal damage to cirrhosis developing in a few months or years in a substantial proportion of transplant recipients. Different virus, host and donor factors are involved in the pathogenesis of recurrence, but many are poorly understood. Therapeutic strategies can be utilized in the pre-, peri- or posttransplantation setting. Antiviral therapy using interferon and ribavirin and modifying immunosuppression are the main strategies to prevent progression disease. The efficacy of interferon and ribavirin is limited and side effects, reduction/withdrawal are frequent. Current sustained virological response rates are approximately 28%. An optimal immunosuppression regimen has not been established. The choice of calcineurin inhibitors has not clearly been shown to affect histological hepatitis C virus (HCV) but higher cumulative exposure to corticosteroids to treat acute rejection is associated with more severe recurrence. The manner in which the doses of immunosuppression are modified has more influence on HCV recurrence than the use of a specific drug per se. Debate about the influence of immunosuppressive regimens on HCV recurrence is ongoing. Potential antifibrotic therapy and new agents targeting HCV infection and replication are emerging and are anticipated to be added to our armentarium in battling recurrent HCV post-LT. PMID- 17355451 TI - Treating hepatitis C in African Americans. AB - BACKGROUND: The epidemiology, natural history and response to therapy of chronic hepatitis C differs significantly between African Americans and other ethnic populations. The reasons for these differences are not entirely clear but include mode of transmission, viral kinetics, immune responsiveness, and demographics. OBJECTIVE: Review of the peer-reviewed literature and expert opinion from 1990 to 2005 regarding features of hepatitis C virus (HCV) infection in African Americans, differences in presentation and response to therapy, and treatment recommendations. RESULTS: The epidemiology of HCV infection in African Americans appears to be predominantly associated with socio-economic status and high-risk behaviors. However, disease course, response to treatment, and virologic outcome may be a function of race. African Americans may clear HCV less efficiently than other ethnic groups, although impaired immune responsivity may also lead to decreased necro-inflammatory activity and progression to cirrhosis. Therapy-naive African Americans have lower sustained virologic response rates to this treatment than other populations. CONCLUSIONS: Strategies to improve outcomes in African Americans include higher doses of current medications, medications with fewer adverse events, and new experimental molecular therapies. PMID- 17355452 TI - Human hepatic progenitor cells express vasoactive intestinal peptide receptor type 2 and receive nerve endings. AB - BACKGROUND: We recently showed that human hepatic progenitor cells (HPCs) express muscarinic acetylcholine (Ach) receptor subtype 3 and that--following liver transplantation--HPC numbers are significantly reduced. To further elaborate on this, we examined whether HPC also express receptors for vasoactive intestinal peptide (VIP), which, besides Ach, also is an important parasympathetic neurotransmitter. VIP expressing nerves are known to be present in the liver. METHODS: We performed immunohistochemistry for VIP receptor subtypes 1 and 2 (VIPR1 and 2), on sections of normal and diseased human liver (n=17), and double staining for VIPR2 and known HPC markers. We performed RT-PCR for VIPR1 and 2 on total RNA from purified rat HPC. To document the probability of direct interaction, we also performed double immunostaining for nerve markers and HPC markers on human liver sections. RESULTS: VIPR2 immunostaining was clearly positive in HPC and reactive bile ductules on paraffin-embedded and frozen tissue sections. We could not demonstrate VIPR1 protein expression in the liver, with either of two VIPR1 antibodies tested. The presence of VIPR2 mRNA in HPC was confirmed by RT-PCR. Nerve endings were shown to abut on reactive bile ductules. CONCLUSION: We show here for the first time that HPC express VIPR2 and receive nerve endings. These features, and the fact that HPC numbers are influenced by the presence or absence of the autonomic innervation of the liver, suggest a direct interaction. PMID- 17355453 TI - MELD score to predict outcome in adult patients with non-acetaminophen-induced acute liver failure. AB - AIMS/BACKGROUND: A model for end stage liver disease (MELD) score >30 was proposed as an excellent predictor of mortality in patients with non acetaminophen-induced acute liver failure (ALF). We analyzed the prognostic value of MELD score in our patients with ALF who were prospectively registered in our database since 1990. METHODS: Overall, 106 patients met the criteria of ALF. Excluding seven patients with acetaminophen etiology, 99 patients (42+/-15 years, 40M/59F) were studied. RESULTS: Causes were cryptogenic (n=38), viral (n=29), drugs (n=20) and miscellaneous (n=12). Of these, 37% (n=37) survived with medical management alone (group I), 16% (n=16) died (group II) and 46% (n=46) underwent liver transplantation (group III). The strongest predictors of poor outcome were advanced encephalopathy, cryptogenic/drug-induced/hepatitis B etiology and a high MELD score. At the time of diagnosis, King's College Hospital criteria and MELD score >30 had similar high negative predictive value (92% and 91%, respectively) and low positive predictive value (52% and 56%, respectively). The predictive values improved only slightly during follow-up. The best cut-off point for MELD score to discriminate between survivors and nonsurvivors was >35, with a sensitivity and specificity of 86% and 75%, respectively. CONCLUSIONS: MELD score, which mostly takes into consideration the degree of liver impairment, has a similar prognostic value as King's College Hospital criteria to predict outcome in adult patients with nonacetaminophen-induced ALF. Overall, all current scores miss accuracy and therefore there is a clear need for factors that can better predict the regeneration of the liver in this setting. PMID- 17355454 TI - Progression to cirrhosis in hepatitis C patients: an age-dependent process. AB - BACKGROUND: Age at infection is known to be associated with disease progression rate in hepatitis C virus (HCV) infected patients. The aim of this study was to assess when cirrhosis is expected to occur according to host and viral factors. METHODS: Fibrosis progression was studied in 247 naive HCV patients using multiple regression analysis. The expected age at cirrhosis was calculated for each patient. RESULTS: Progression rate was 0.13, 0.14, 0.27, and 0.36 U of fibrosis/year for patients with age at infection or=37 years, respectively. Age at infection above 37 years was independently associated with fast progression (rate>0.13; P=0.001). Body mass index >25 kg/m2 and alanine aminotransferase>3 x ULN are also possibly associated with faster progression. Based on progression rates, the expected age at cirrhosis is 65.4, 64.6, 64.8 and 69.4 years for age at infection or=37 years, respectively. CONCLUSION: Most HCV patients, if untreated, are expected to develop cirrhosis at about 65 years, irrespective of the age at infection. Thus, age itself seems even more important than age at infection for predicting the occurrence of liver cirrhosis. A specific active monitoring and therapeutic approach should be adopted in older patients to prevent progression to cirrhosis and its complications. PMID- 17355455 TI - Treatment and retreatment in patients with chronic hepatitis C: 10 years clinical practice in a single centre. AB - AIM: Therapy for chronic hepatitis C (HCV) has mainly been evaluated in large clinical, select population, trials. We sought to evaluate whether prognostic factors of therapeutic response are similar in clinical practice, where treated population is more diverse. METHODS: Retrospective study of HCV-infected patients who completed >6 months of treatment/retreatment with various therapeutic regimens, in a single reference centre over a 10-year period. Adjuvant treatment with hemopoetic growth factors was used when warranted by treatment side effects. RESULTS: Overall, 77/125 patients (61.6%) achieved sustained virological response (SVR). Fifty-four naive patients (43.2%) achieved SVR; 19 (26%) with interferon alpha (IFN-alpha), 13 (59.1%) with IFN-alpha and ribavirin, and 22 (73.3%) with pegylated IFN-alpha and ribavirin. Seventeen patients responded after two courses of therapy and six after more than three courses, achieving a total SVR of 32%. Patients with genotype-1 were less probable to achieve SVR [odds ratio (OR)=6.23], while younger patients were more possible to achieve SVR, OR=0.97. Most non-responders after >2 regimens were genotype-1 patients (90%). CONCLUSIONS: In clinical practice, where strict selection criteria cannot be applied, genotype-1 remains the most significant prognostic factor of response failure. Addition of adjuvant hemopoetic growth factors, when warranted, may increase compliance and thus overall SVR. PMID- 17355456 TI - Endoscopic intraluminal brachytherapy and metal stent in malignant hilar biliary obstruction: a pilot study. AB - BACKGROUND/AIMS: Malignant hilar biliary obstruction carries a poor prognosis, as the disease is often unresectable at the time of diagnosis. Various palliative measures as surgical/radiological/ endoscopic drainage with or without radiotherapy/chemotherapy have been tried with dismal outcome. We prospectively studied the effect of unilateral metal stent with intraluminal high dose rate (HDR) brachytherapy in patients with type II malignant hilar biliary obstruction. METHODS: Eight patients with type II malignant hilar biliary obstruction were treated with contrast-free unilateral metal stenting followed by endoscopic intraluminal brachytherapy (ILBT). A retrospectively analyzed group of 10 patients treated only with contrast-free unilateral metal stenting served as historical controls. RESULTS: A successful drainage was achieved in all, cholangitis occurred in none and no patient died within 30 days in both groups. The mean (+/-SD) patency of metal stent was 305 (+/-183.96) days and 143.9(+/ 115.11) days in patients with and without intraluminal brachytherapy, respectively (P=0.03). Mean (+/-SD) survival of these patients was 310 (+/ 192.68) days and 154.9 (+/-122.51) days in patients with and without intraluminal brachytherapy, respectively (P=0.05). Kaplan-Meier analysis showed estimated median survival of 225 (95% CI; 169.5, 280.4) days in brachytherapy and 100 (95%CI; 94.1, 105.8) days in control group (P=0.025). No major complications related to metal stent or ILBT were observed. CONCLUSIONS: Contrast-free unilateral metal stenting with HDR ILBT in type II malignant hilar biliary obstruction is a safe and effective method of palliation and appears to prolong patient survival as well as patency of stent in these patients, however, a larger, randomized trial is required to validate the same. PMID- 17355457 TI - Randomized controlled trial for the efficacy of hepatic arterial occlusion during radiofrequency ablation for small hepatocellular carcinoma--direct ablative effects and a long-term outcome. AB - OBJECTIVE: To evaluate the efficacy of temporary balloon arterial occlusion during radiofrequency ablation (RFA), randomized controlled trial was performed. METHODS: Twenty patients with hypervascular hepatocellular carcinoma measuring 25 kg/m2 and 524 control patients with BMI C in intron 21 and c.4582 - 19A > G in intron 35, were also observed in normal controls with estimated frequencies of 0.06 and 0.15, respectively. CONCLUSIONS: We could not identify any FBN1 variations possibly associated with SCH in our study population. PMID- 17355505 TI - Intracranial carotid dissection. PMID- 17355506 TI - Evaluation and management and current procedural terminology coding for headache. PMID- 17355507 TI - Migrainous visual auras: a life history. AB - We document, as an autobiographical case report, a 72-year history of migraine and its changing nature. Minor neurological events have waxed and waned, causing repeated searches for pathology, but instead reconfirming an intact central nervous system. In this case it appears that visual migraine auras do not reflect severity of pathology. Visual auras of migraine are cyclical in frequency and intensity and may have remissions as long as 15 years. PMID- 17355508 TI - Hemicrania continua-like headache associated with internal carotid artery dissection may respond to indomethacin. AB - Hemicrania continua (HC) is an idiopathic, chronic disorder characterized by a continuous, strictly unilateral headache associated with ipsilateral cranial autonomic symptoms. The symptoms of HC typically respond dramatically to indomethacin therapy. We describe a patient with traumatic internal carotid artery dissection, who presented with a clinical picture mimicking HC that initially responded to indomethacin. Patients with a clinical picture similar to HC should be managed with a high index of suspicion for a possible cervical arterial dissection. PMID- 17355509 TI - Hashimoto's encephalopathy mimicking migraine with aura. AB - We describe a patient with Hashimoto's encephalopathy presenting as long-standing episodes of aphasia associated with migraine-like headache. Repeated thyroid hormone levels were within normal values, but high titers of antithyroid antibodies in serum, and diffuse EEG slowing and CSF abnormalities during one episode led to the diagnosis. PMID- 17355510 TI - Patulous Eustachian tube in spontaneous intracranial hypotension syndrome. AB - A 48-year-old slender woman presented with a rare case of spontaneous intracranial hypotension syndrome manifesting as patulous Eustachian tube. The patient complained of sudden onset of ear fullness and nasal voice as well as typical orthostatic headache. Patulous Eustachian tube was identified by observation of synchronous movement of the tympanic membrane with respiration and swallowing. The diagnosis of spontaneous intracranial hypotension was confirmed by negative cerebrospinal fluid pressure, and typical magnetic resonance imaging and radioisotope cisternography findings. All symptoms completely resolved within a few days after epidural blood patch treatment. Changes in the venous blood distribution led by collapse of the dural sac of the cervical spine in the standing position presumably caused decreased size of the pterygoid venous plexus around the Eustachian tube. PMID- 17355511 TI - Is migraine a cardiac disorder? PMID- 17355512 TI - Headaches should be conceptualized within the framework of the biopsychosocial model. PMID- 17355514 TI - Topiramate for chronic migraine. PMID- 17355515 TI - Closing the 10/90 divide in global mental health research. PMID- 17355516 TI - The case for long-acting antipsychotic agents in the post-CATIE era. AB - OBJECTIVE: Long-acting antipsychotic agents were developed to promote treatment compliance in patients requiring maintenance treatment for schizophrenia. METHOD: An analysis of the impact of non-compliance on treatment outcomes in schizophrenia and the advantages and disadvantages of long-acting antipsychotics. RESULTS: Partial or total non-compliance with oral antipsychotics remains widespread and is associated with significant increases in the risk of relapse, rehospitalization, progressive brain tissue loss and further functional deterioration. Long-acting agents have the potential to address issues of all cause discontinuation and poor compliance. The development of the first long acting atypical antipsychotic, which appears to be effective and well tolerated, should further improve the long-term management of schizophrenia. CONCLUSION: Long-acting agents represent a valuable tool for the management of schizophrenia and merit wider use, especially in light of emerging literature regarding the neuroprotective advantages of atypical antipsychotics over conventional agents in terms of regenerating brain tissue during maintenance therapy. PMID- 17355517 TI - Prolactin level during 5 years of risperidone treatment in patients with psychotic disorders. AB - OBJECTIVE: To investigate prolactin levels and related side effects in 128 men and 90 women initially treated with risperidone. METHOD: Patients initially treated with risperidone were followed over 5 years, during which 45% were switched to other antipsychotic drugs. RESULTS: Initially, prolactin levels were fivefold the norm in women, and threefold in men. Diagnosis did not affect the prolactin level if adjustment for sex, current age, and age at onset of psychosis was applied. Prolactin levels did not correlate significantly neither with any Positive and Negative Symptom Scale item or subscale, nor with side effects. Drugs other than risperidone were not associated with high prolactin levels. For patients on continuous monotherapy risperidone treatment, there was a marked linear reduction of prolactin level over all 5 years. CONCLUSION: Risperidone induces a higher prolactin elevation than other atypical antipsychotics, but the effect adapts over time. Prolactin was not associated with expected side effects (e.g. sexual, mental, or weight gain). PMID- 17355518 TI - Weight development in patients treated with risperidone: a 5-year naturalistic study. AB - OBJECTIVE: To examine annual weight-development in a sample of 215 psychotic patients treated with risperidone over 5 years. METHOD: Naturalistic longitudinal study. RESULTS: The sample was more obese than the general population at baseline, but also increased much more in mean body mass index over approximately the same time period, while patients off medication seemed to remain weight stable. Excessive weight gain (>7%) was experienced by 40.2% and was weakly associated with weight at baseline (beta = -0.2%; P = 0.02), while independent of gender, symptoms, years of illness, prolactin levels and nicotine consumption. In patients with complete weight data (n = 87), approximately 72% (3.4 +/- 8.3 kg) of the observed 5 years weight gain (4.7 +/- 11.6 kg) had been accumulated after 2 years. CONCLUSION: Antipsychotic drug treatment resulted in significant weight gain, which levelled off over time. Unfortunately, few significant predictors of adverse weight development could be identified, leaving little guidance for clinical decision making regarding this specific side-effect. PMID- 17355519 TI - Long-term maintenance of weight loss in patients with severe mental illness through a behavioural treatment programme in the UK. AB - OBJECTIVE: Obesity is common among people with severe mental illness (SMI). We report our experience from the first 4 years of The Cromwell House weight management clinic. METHOD: Ninety-three patients with SMI aged 43.7 +/- 1.2 years referred themselves to this clinic. The patients were seen in weekly group sessions that involved weight measurement, discussion and education. RESULTS: Mean baseline weight was 89.5 +/- 1.8 kg [body mass index (BMI) 32.3 +/- 0.5 kg/m(2)]. Twenty-three per cent dropped out within the first 8 weeks. There was progressive statistically significant reduction in mean weight and BMI throughout the duration of monitoring with no suggestion of a plateau. The mean final weight loss was 6.2 +/- 0.6 kg. Weight loss was correlated only with the number of sessions attended (r = 0.53, P < 0.0001). CONCLUSION: Long-term weight management of obese and overweight patients with severe forms of mental illness was possible through the provision of simple lifestyle advice within the group setting. PMID- 17355520 TI - Comparative study of neurological soft signs in schizophrenia with onset in childhood, adolescence and adulthood. AB - OBJECTIVE: To compare neurological soft signs (NSS) in patients of schizophrenia with onset in childhood (COS), adolescence (AdOS) and adulthood (AOS). METHOD: Assessment of NSS in 15 patients of COS and 20 patients each of AdOS and AOS was made using condensed neuropsychiatric examination for NSS. RESULTS: NSS were significantly more frequent in COS (100%) and AdOS (90%) when compared with AOS (55%) patients. COS patients showed significantly higher scores on temporal and frontal lobe NSS, of which differences between the three groups in temporal lobe NSS disappeared on ancova. Parietal lobe dependent NSS were seen in a few COS patients. The NSS were more in those with lesser IQ, lower education and higher Positive and Negative Syndrome Scale scores. CONCLUSION: Findings indicate that earlier onset types may be more strongly associated with a generalized disruption of brain function. Non-suppression of primitive reflexes with cortical maturation in COS point towards disordered neurodevelopment. Preponderance of fronto temporal and a relative lack of parietal lobe NSS point towards differential lobar involvement. Neurodevelopmental abnormalities leading to NSS also lead to lower IQ and lower educational level. PMID- 17355521 TI - Patterns, predictors and impact of substance use in early psychosis: a longitudinal study. AB - OBJECTIVE: The purpose was to determine the prevalence of substance use and its impact on outcome 3 years after presentation for a first-episode of psychosis. METHOD: Subjects were 203 consecutive admissions to an early psychosis program. Assessments included substance use, positive, negative and depressive symptoms and social functioning. Assessments occurred at baseline, and 1-, 2- and 3-year follow-ups. RESULTS: The prevalence of substance misuse was high with 51% having a substance use disorder (SUD), 33% with cannabis SUD and 35% with an alcohol SUD. Numbers with an alcohol SUD declined considerably by 1 year and for cannabis SUD by 2 years. Substance misuse was significantly associated with male gender, young age and age of onset and cannabis misuse with increased positive symptoms. CONCLUSION: This study confirms the high rates of substance misuse, in particular cannabis, in first-episode psychosis. It further demonstrates that these rates can be reduced. PMID- 17355522 TI - Patterns of social distance towards people suffering from schizophrenia in Austria: a comparison between the general public, relatives and mental health staff. AB - OBJECTIVE: The aims of this study were to identify the different aspects of the attitudes towards people suffering from schizophrenia and to find factors influencing these attitudes -- especially the willingness to contact people suffering from schizophrenia -- as well as to obtain information on how to reduce stigma and discrimination. METHOD: We conducted a study to investigate these attitudes in Austria. A representative sample of the general public, different professional groups working in the field and relatives of mentally ill people were interviewed. The public, relatives and people working in the mental health field were asked a number of the same questions, to allow for comparisons between groups. RESULTS: We found great differences in key dimensions of the attitude towards people suffering from schizophrenia between groups: these included different causal attributions to schizophrenia, different attitudes concerning the perceived success of the treatment of schizophrenia, different fears concerning perceived dangerousness and a different willingness to interact voluntarily with schizophrenia patients. CONCLUSION: The factors influencing the distance towards people suffering from schizophrenia differ between groups. Our findings should help to optimize campaigns fighting against stigma and discrimination. PMID- 17355523 TI - Avoidable mortality of psychiatric patients in an area with a community-based system of mental health care. AB - OBJECTIVE: To ascertain the existence of an excess of avoidable mortality among psychiatric patients in an area with a community-based system of care, to identify predictors of higher risk of avoidable mortality and to provide some possible indication to reduce avoidable mortality in modern psychiatric services. METHOD: All patients with an ICD-10 psychiatric diagnosis, living in a catchment area of about 75,000 inhabitants, seeking care in 1982-2001 were included (n = 6956). Mortality and causes of death were ascertained using linkage procedures with other local health databases. Standardized mortality ratios (SMRs) were calculated for each avoidable cause of death. RESULTS: The observed number of deaths for those causes considered avoidable by the European Community was four times greater than the expected (P < 0.01). SMR was higher for deaths preventable with adequate health promotion policies than for those preventable with appropriate health care. Males, alcohol/drug addicted and young patients have the highest avoidable SMRs. CONCLUSION: These findings urgently call for the implementation of health promotion and preventive programs targeted to psychiatric patients. Moreover, mental health services should improve the capacity to manage medical health problems of their patients. PMID- 17355524 TI - Are GAF scores reliable in routine clinical use? AB - OBJECTIVE: The Global Assessment of Functioning (GAF) scale has been considered as a reliable tool. However, most studies of GAF reliability have been based on special conditions, such as prior training and test awareness. This study takes a different approach investigating inter-rater reliability of GAF scores in a routine clinical context. METHOD: Eighty-two consecutively admitted acute psychiatric patients were rated according to routine department procedures and by two researchers at admission and discharge. Intraclass correlations (ICC) were computed using two-way mixed models. RESULTS: Inter-rater reliability between routine scores and research scores were low (ICC coefficients between r = 0.39 and 0.59). Inter-rater reliability between the two researchers were excellent (ICC coefficients r = 0.81 and 0.85). CONCLUSION: Inter-rater reliability of GAF scores in a routine clinical context seems to be insufficient. PMID- 17355525 TI - The destinies of the low- and middle-income country submissions. AB - OBJECTIVE: To measure the number of submissions to Acta Pyschiatrica Scandinavica from low- and middle-income countries (LIC/MIC) compared with submissions from high income countries (HIC), to compare the way through the peer review process for the three groups respectively, as well as how they do as published articles eventually. METHOD: By help of the Acta Psychiatrica Scandinavica editorial office database all submissions of reviews of the literature, clinical overviews, original articles, brief communications, and case reports from 2002 through 2005 were analysed as to external/in-house review, acceptance/rejection, number of downloads from Blackwell-Synergy, and number of citations [Institute of Scientific Information (ISI)] in a comparison between HIC and LIC/MIC. RESULTS: About 14.6% of the total submissions in 2002/2003 came from LIC and MIC countries, 15.5% for the 2004/2005 period. In both periods, a larger portion of LIC/MIC manuscripts were reviewed exclusively in-house compared with HIC ones and among those papers reviewed by external experts a smaller proportion of the submissions from HIC countries were rejected than of those from LIC and MIC countries. From the first to the second period there is a significant increase of proportion of submitted LIC/MIC papers accepted for publication compared with HIC papers. Full text download and citation statistics did not differ significantly between HIC and LIC/MIC. CONCLUSION: Low- and middle-income countries manuscripts do gradually better in the competition with HIC papers in Acta Psychiatrica Scandinavica. The major observation is that the total number of LIC/MIC submissions to the journal is still low. PMID- 17355527 TI - Re: good school performance is a risk factor of suicide in psychoses: a 35-year follow up of the Northern Finland 1966 Birth Cohort. PMID- 17355528 TI - Biography. PMID- 17355529 TI - Modafinil improves primary nocturnal enuresis in multiple sclerosis. PMID- 17355530 TI - Suicidal attempts and aggressive behaviours after temporal lobectomy in epilepsy. PMID- 17355531 TI - Sensory Guillain-Barre syndrome after Campylobacter jejuni infection. PMID- 17355537 TI - Treatment policies for alcohol-related seizures: a survey of European neurologists. PMID- 17355538 TI - Is there still a role for edrophonium in diagnosing ocular myasthenia. PMID- 17355539 TI - Hypomania complicating topiramate therapy for migraine prophylaxis. PMID- 17355540 TI - Tramazoline turns asymptomatic into symptomatic hyper-CK-emia. PMID- 17355541 TI - Unusual triad due to a bilateral medial medullary infarction in a 35-year-old man. PMID- 17355542 TI - One Europe, one neurologist? AB - In recent years, there has been a major shift in emphasis within neurology from being a largely diagnostic discipline to one much more actively involved in treating disease. There have been major scientific advances leading to new and effective treatments. There is also a much greater awareness of the burden of neurological disease (Olesen J, Leonardi M. European Journal of Neurology 2003; 10: 471) and informed sufferers are requesting specific intervention. There is wide variation in the delivery of neurological services throughout Europe. This is reflected in manpower levels, the place of neurology related to other medical specialties and different mixes of hospital and private office practice. These differences have been thrown into sharper focus by the recent expansion of the European Union (EU). Initial training in neurology is given to undergraduate/pre graduate students. Post-graduate education is delivered within a residency program leading to specialist qualification and certification. We now recognize that this is only the beginning of a life long program of continuous education and development (CME/CPD). National and international exchange programs facilitate the growth of knowledge and promote professional harmony and cooperation. The free migration of medical specialists has been an aspiration but remains limited by cultural, linguistic, personal, professional, political and economic factors. Two bodies, the European Board of Neurology (EBN-UEMS) http://www.uems-neuroboard.org (Union Europeenne des Medecins Specialistes) and the European Federation of Neurological Societies (EFNS) http://www.efns.org are actively involved in harmonising and developing neurology at the European level. PMID- 17355543 TI - Ventricular cerebrospinal fluid neurofilament protein levels decrease in parallel with white matter pathology after shunt surgery in normal pressure hydrocephalus. AB - Normal pressure hydrocephalus (NPH) is characterized by disturbed cerebrospinal fluid (CSF) dynamics and white matter lesions (WML). Although the morphology of these lesions is described, little is known about the biochemistry. Our aim was to explore the relationship between ventricular CSF markers, periventricular WML and postoperative clinical outcome in patients with NPH. We analysed lumbar and ventricular concentrations of 10 CSF markers, 12 clinical symptoms and signs, magnetic resonance imaging (MRI) periventricular white matter hyperintensities (PVH) and ventricular size before and 3 months after shunt surgery in 35 patients with NPH. Higher ventricular CSF neurofilament protein (NFL), an axonal marker, correlated with more extensive PVH. A larger postoperative reduction in NFL correlated with larger reduction in PVH and a more pronounced overall improvement. Albumin ratio, HMPG, NPY, VIP and GD3 increased postoperatively whereas NFL, tau and HVA decreased. Variations in ventricular size were not associated with CSF concentrations of any marker. We conclude that NPH is characterized by an ongoing periventricular neuronal dysfunction seen on MRI as PVH. Clinical improvement after shunt surgery is associated with CSF changes indicating a restitution of axonal function. Other biochemical effects of shunting may include increased monoaminergic and peptidergic neurotransmission, breakdown of blood brain barrier function, and gliosis. PMID- 17355544 TI - Variations in the use of diagnostic procedures after acute stroke in Europe: results from the BIOMED II study of stroke care. AB - Valid classification of stroke is essential to initiate effective acute management and early secondary prevention strategies. To accurately evaluate stroke subtype a number of diagnostic procedures have to be performed. This study sought to investigate variations in use of diagnostic procedures across selected European hospitals. First-ever stroke patients were sampled over a 1-year period through 11 hospital-based registers across 10 European countries. We defined a diagnostic standard for valid aetiological classification of ischemic stroke including brain imaging, vascular imaging and echocardiography. The impact of socio-demographic, clinical and structural characteristics on performance of the diagnostic standard was assessed using multivariate logistic regression analyses. A total of 1721 patients were included in the study. 83.1% received brain imaging, ranging from 32.8% to 100%. The diagnostic standard was performed in 40.4% of stroke patients, ranging from 0% to 77.2%. Patients with increasing age (P < 0.001) and with more severe strokes (P = 0.001) were less probably to receive the diagnostic standard. Patients treated in stroke units and neurological departments were more frequently investigated with the diagnostic standard (P < 0.001). Less than half of hospitalized stroke patients across Europe underwent diagnostic procedures to allow for aetiological classification of stroke, which may hamper the initiation of effective early management and secondary prevention. PMID- 17355545 TI - Riluzole and amyotrophic lateral sclerosis survival: a population-based study in southern Italy. AB - Riluzole is to date the only treatment that prolongs amyotrophic lateral sclerosis (ALS) survival. However, results on the efficacy of riluzole in observational population-based studies with a longer follow-up are conflicting and it is still unclear if the effect of the drug is limited to an early stage of the disease and to some specific subgroups of patients. The objective is: (i) to evaluate the effect of riluzole on ALS survival in a cohort of incident cases; (ii) to examine whether bulbar-ALS benefits from the medication to a greater extent and (iii) to assess the efficacy of the drug in elderly patients. Source of the study was a prospective population-based registry of ALS established in Puglia, Southern Italy. We examined survival of 126/130 incident ALS cases diagnosed during the period 1998-1999. Seventy-three patients were prescribed riluzole and the remaining 53 were not. Riluzole therapy increased survival rates at 12 months by approximately 10% and prolonged survival by 6 months (18.2 months vs. 12.4; peto-test: 2.78; P = 0.09). This beneficial effect was present amongst bulbar-onset ALS (peto-test: 4.11; P = 0.042), but not in subjects with limb onset (peto-test: 0.48; P = 0.4). In patients aged >70 years riluzole treatment was associated with an 8 months longer median survival time [15.4 months vs. 7.1] and a reduction in mortality rate at 12 months by 27%, regardless of site of symptoms onset. In multivariate analysis, riluzole use was an independent predictor of survival at 12 months from the diagnosis with borderline significance (P = 0.06). Riluzole was effective amongst cases with bulbar-onset ALS (P = 0.04), whereas in subjects with limb-onset there was no effect on survival at 12 months (P = 0.5). In each model riluzole did not influence survival at 24 months. Conversely, riluzole use was associated with an improvement in survival amongst elderly patients both at 12 (P = 0.07), at 24 months (P = 0.03) and in the entire follow-up period (P < 0.04). In this population-based series, we found that riluzole therapy improves ALS survival. The efficacy of the drug was present amongst bulbar-onset ALS and older patients, but not in subjects with limb-onset. The favourable effect of the drug was transient, as it was lost in prolonged follow-up. Our observations support the use of riluzole at an early stage of ALS in bulbar and elderly patients. However, the appropriate duration of riluzole treatment remains to be established. PMID- 17355546 TI - Crossover, double-blind clinical trial comparing almotriptan and ergotamine plus caffeine for acute migraine therapy. AB - In this randomized, double-blind, crossover clinical trial, adult patients treated two migraine attacks: one with almotriptan 12.5 mg and the other with ergotamine 2 mg plus caffeine 200 mg. Treatment with almotriptan was associated with a significantly greater proportion of patients achieving 2-h pain free (20.9% vs. 13.7%; P < 0.05) and 2-h pain relief (57.7% vs. 44.5%; P < 0.01) compared with ergotamine plus caffeine therapy; significant differences were not seen at 1 h. Rates for sustained pain free and sustained pain free plus no adverse events (AEs) also were significantly greater after almotriptan treatment than after the use of ergotamine plus caffeine (P < 0.05). Almotriptan was associated with a significantly lower rate of photophobia at 90 min (P < 0.05), phonophobia at 60, 90, and 120 min (P < 0.05 to <0.01), and nausea and vomiting at 90 and 120 min (P < 0.01) compared with ergotamine plus caffeine. A significantly greater proportion of patients were more satisfied with almotriptan than with ergotamine plus caffeine (P < 0.05). Sixteen patients reported adverse events during almotriptan treatment and 27 patients reported AEs during the ergotamine plus caffeine therapy. Most AEs were mild-to-moderate and did not result in treatment-related discontinuations. In conclusion, almotriptan was associated with significantly greater efficacy for treating migraine compared with ergotamine plus caffeine, was generally well tolerated and was associated with greater rate of treatment satisfaction. PMID- 17355547 TI - Acupuncture treatment improves nerve conduction in peripheral neuropathy. AB - The etiology of peripheral neuropathy (PN) often remains elusive resulting in a lack of objective therapeutic strategies. We conducted a pilot study to evaluate the therapeutic effect of acupuncture on PN as measured by changes in nerve conduction and assessment of subjective symptoms. One hundred and ninety-two consecutive patients with PN as diagnosed by nerve conduction studies (NCS) were evaluated over a period of 1 year. Of 47 patients who met the criteria for PN of undefined etiology, 21 patients received acupuncture therapy according to classical Chinese Medicine as defined by the Heidelberg Model, while 26 patients received the best medical care but no specific treatment for PN. Sixteen patients (76%) in the acupuncture group improved symptomatically and objectively as measured by NCS, while only four patients in the control group (15%) did so. Three patients in the acupuncture group (14%) showed no change and two patients an aggravation (10%), whereas in the control group seven showed no change (27%) and 15 an aggravation (58%). Importantly, subjective improvement was fully correlated with improvement in NCS in both groups. The data suggest that there is a positive effect of acupuncture on PN of undefined etiology as measured by objective parameters. PMID- 17355548 TI - Long-term effectiveness and quality of life improvement in entacapone-treated Parkinson's disease patients: the effects of an early therapeutic intervention. AB - To evaluate the long-term effects of entacapone on both mean daily 'on' time and health-related quality of life (QoL) in patients with Parkinson's disease (PD) experiencing 'end-of-dose' motor fluctuations and the benefits of an early therapeutic intervention. A prospective, multicenter, observational, 12-month study was performed with an initial 3-month intervention phase, consisting of a phone call to half of the patients from randomly selected investigators to assess if dose adjustment was necessary. Effectiveness was determined by home diaries ('on' time), subscales II and III of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Parkinson's Disease Questionnaire (PDQ-8). After 3 months of treatment, 4.0% of the intervention group patients discontinued the study, versus 18.4% in the control group (P < 0.01). The improvement in 'on' time was significantly increased since the 3-month visit (21%, P < 0.0001) until the end of the study (23% at 12 months, P < 0.0001). Entacapone also induced significant reductions in the UPDRS scores for subscales II and III and in the PDQ-8 score. 11.2% of patients experienced at least one adverse reaction. This study confirms the effectiveness of entacapone in reducing motor fluctuations by increasing 'on' time, and in improving QoL of PD patients. An early adjustment of entacapone and levodopa doses reduces the number of treatment discontinuations during the first months of treatment. PMID- 17355549 TI - Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. AB - Symptoms relating to spasticity are common in multiple sclerosis (MS) and can be difficult to treat. We have investigated the efficacy, safety and tolerability of a standardized oromucosal whole plant cannabis-based medicine (CBM) containing delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), upon spasticity in MS. A total of 189 subjects with definite MS and spasticity were randomized to receive daily doses of active preparation (n = 124) or placebo (n = 65) in a double blind study over 6 weeks. The primary endpoint was the change in a daily subject-recorded Numerical Rating Scale of spasticity. Secondary endpoints included a measure of spasticity (Ashworth Score) and a subjective measure of spasm. The primary efficacy analysis on the intention to treat (ITT) population (n = 184) showed the active preparation to be significantly superior (P = 0.048). Secondary efficacy measures were all in favour of active preparation but did not achieve statistical significance. The responder analysis favoured active preparation, 40% of subjects achieved >30% benefit (P = 0.014). Eight withdrawals were attributed to adverse events (AEs); six were on active preparation and two on placebo. We conclude that this CBM may represent a useful new agent for treatment of the symptomatic relief of spasticity in MS. PMID- 17355550 TI - Striatal dopamine transporter binding in patients with Parkinson's disease and severe occupational hydrocarbon exposure. AB - We used 123I-Ioflupane SPECT to study striatal dopamine transporter (DAT) binding in 36 Parkinson's disease (PD) patients with history of severe occupational exposure to hydrocarbons. Data were compared with 38 PD patients without exposure history as well as healthy controls. Both PD cohorts showed significant striatal uptake decrements compared with controls. We found significantly lower values in the whole striatum of exposed compared with non-exposed patients (0.83 +/- 0.25 vs. 1.05 +/- 0.39; P = 0.004), more pronounced in the putamen (0.61 +/- 0.24 vs. 0.85 +/- 0.42; P = 0.004). We conclude that severe occupational exposure to hydrocarbons may modify disease course and ultimately accelerate nigro-striatal denervation. PMID- 17355551 TI - Behavioral persistence deficit in Parkinson's disease patients. AB - The present study was performed to examine the degree to which decreased task persistence may contribute to deficits in the ability of Parkinson's disease (PD) patients to perform a problem solving task. Patients with mild/moderate PD performed a computerized Tower of Hanoi task in which they planned and verbalized moves to solve the puzzle but did not need to produce a limb motor response. All patients were tested at least 14 h off medication. As expected from previous studies of planning abilities in PD, patients had significant problems performing this task and accuracy decreased specifically when patients were presented with the most difficult puzzles in the sequence. PD patients solved fewer of the most difficult puzzles than did control subjects, but also made significantly fewer attempts to solve those puzzles than controls. These results suggest that PD patients not only have planning and problem solving deficits as have been documented previously, but that at least part of this and perhaps other cognitive performance problems may result from difficulty in maintaining adequate mental effort to successfully complete difficult tasks. PMID- 17355553 TI - Disseminated necrotizing leukoencephalopathy following low-dose oral methotrexate. AB - Leukoencephalopathy is a recognized complication with intrathecal or intravenous methotrexate (MTX). We report a 59-year-old lady who developed MTX leukoencephalopathy with long-term low-dose oral MTX. She developed posterior leukoencephalopathy (PLE) that initially was reversible on discontinuation of oral MTX. Four months later, she developed disseminated necrotizing leukoencephalopathy (DNL), and was left with devastating neurological deficits. The sequential conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), MR perfusion (MRP) and MR spectroscopic (MRS) changes are highlighted in this report. MRP and MRS showed more wide spread abnormalities than DWI. Stereotactic biopsy from the lesion revealed demyelination with macrophagic infiltration, pericapillary lymphomononuclear aggregation, fibrinoid changes in the capillaries and neovascularization. Of the two cases of PLE with oral MTX reported in literature, one reversed clinically and radiologically with the discontinuation of MTX. To the best of our knowledge, this is the first reported case of DNL following oral MTX in the world literature. PMID- 17355552 TI - Co-morbidity of Emery-Dreifuss muscular dystrophy and a congenital myasthenic syndrome possibly affecting the phenotype in a large Bedouin kindred. AB - Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked humero-peroneal muscular dystrophy associated with contractures and cardiomyopathy. In a 90 member family, we found 11 affected male individuals, three of whom displayed areflexia and neurogenic electromyographic changes. Muscle biopsy performed in one case demonstrated type grouping suggestive of a neurogenic disorder. These three individuals and another family member, who suffers from mild, static limb weakness but is clinically and genetically unaffected by EDMD showed an abnormal incremental response of over 100% to tetanic stimulation. In contrast, one affected family member showed myopathic features on needle electromyography and no definite pathology in repetitive stimulation studies. The diagnosis of EDMD was established by demonstrating a 1712_1713insTGGGC mutation in the emerin gene. This family apparently expresses co-morbidity of EDMD with an exceptionally mild form of pre-synaptic congenital myasthenic syndrome resembling the Lambert-Eaton myasthenic syndrome (LEMS). The superimposed pre-synaptic disorder may have contributed to the development of the neurogenic features demonstrated in these patients. PMID- 17355554 TI - Triggered C-reactive protein (CRP) concentrations and the CRP gene -717A>G polymorphism in acute stroke or transient ischemic attack. AB - C-reactive protein (CRP) increases following an acute stroke/transient ischemic attack (TIA), but the increment level varies among patients. We analyzed CRP concentrations during an acute stroke/TIA in relation to the CRP gene -717A>G polymorphism. Six months following an acute ischemic stroke/TIA, basal concentrations of CRP were measured in 507 controls and 219 patients and were found to be unassociated with the CRP -717A>G polymorphism. However, during the acute phase of stroke/TIA, individuals with the AG/GG genotype had significantly elevated CRP concentrations as opposed to those with the AA genotype (2.02 +/- 1.59 vs. 1.73 +/- 1.69 mg/l, P = 0.027). In addition, significant 3.22-fold increments in CRP concentrations was noted in individuals carrying the -717G allele when comparing the acute phase with the basal state of each patient and averaging the results. CRP -717A>G polymorphism is associated with triggered CRP concentrations during acute stroke/TIA. These findings might shed more light on the mechanisms of CRP elevation in acute ischemic stroke/TIA. PMID- 17355555 TI - Sleep disordered breathing in medically stable patients with myasthenia gravis. AB - We investigate sleep and breathing in clinically stable myasthenia gravis (MG) patients and ask weather sleep disordered breathing (SDB) is causally linked with MG. Nineteen MG patients with a mean disease duration of 9.7 years underwent sleep studies in two consecutive nights. The primary outcome measure was the respiratory disturbance index (RDI) in terms of snoring and apneas/hypopneas. Further outcome measurements were total sleep time, sleep stage distribution and the number of arousals. A clinically relevant SDB in terms of obstructive sleep apnea (OSA) (defined as RDI > 10/h) was found in four patients. There were only a few central apneas (central apnea index: 0.19 +/- 0.4/h). We did not find a relationship between maximum inspiratory pressure and SDB (r = -0.03). There is no evidence for a causal relationship between medically stable MG and SDB in terms of OSA. The extent of respiratory muscle weakness failed to correlate with SDB. Furthermore, our study does not confirm the high occurrence of central respiratory events during sleep in patients with well-controlled MG. PMID- 17355556 TI - Immune reactivity towards insulin, its amyloid and protein S100B in blood sera of Parkinson's disease patients. AB - Peripheral immune responses can be sensitive indicators of disease pathology. We evaluated the autoimmune reactions to endocrine (insulin) and astrocytical (S100B) biomarkers in the blood sera of 26 Parkinson's disease (PD) patients compared with controls by using ELISA. We found a statistically significant increase of the autoimmune responses to both antigens in PD patients compared with controls with a mean increase of 70% and 50% in the autoimmune reactions towards insulin and S100B, respectively. Heterogeneity of the immune responses observed in patients may reflect the modulating effect of multiple variables associated with neurodegeneration and also changes in the basic mechanisms of individual autoimmune reactivity. We did not detect any pronounced immune reactions towards insulin amyloid fibrils and oligomers in PD patients, indicating that an amyloid-specific conformational epitope is not involved in immune recognition of this amyloid type, while sequential epitope of native insulin is hidden within the amyloid structures. Immune reactions towards S100B and insulin may reflect the neurodegenerative brain damaging processes and impaired insulin homeostasis occurring in PD. PMID- 17355557 TI - Microvascular decompression for hemifacial spasm: postoperative neurologic follow up and evaluation of life quality. AB - Microvascular decompression (MVD) is an effective and safe treatment in hemifacial spasm (HFS). Postoperative evaluations are usually made by neurosurgeons. Follow-up studies performed by neurologists and postoperative quality of life (QoL) investigations are lacking. All 25 HFS patients operated with MVD in our centre between 2000 and 2004 were evaluated with the recently validated HFS-7 scheme, extended with the item 'sleep disturbance due to HFS' (HFS-8). The patients underwent a careful neurological examination median 3 years after the operation. The evaluation focused on clinical aspects, changes in blood pressure and time until observable effect of MVD. The evaluation of HFS-7 questionnaire and the extended form (HFS-8) showed significant improvement in QoL after MVD. Neurological outcome was in almost all cases excellent or good. Eleven (44%) patients had no neurological deficits at all. Only one patient had serious complications with ipsilateral facial palsy, deafness, balance problems and vertigo. The other patients had minor neurological findings or symptoms. Eighteen (72%) patients experienced early effect within 3 months after MVD; seven (28%) patients had late effect between 6 and 14 months. Median age of the patients with late effect (62.6 years) was significantly higher than in those with early effect (52.7 years). PMID- 17355558 TI - Patent foramen ovale management: who should do what? AB - Although definitive evidence of effectiveness of percutaneous patent foramen ovale (PFO) closure is still debated and closure seems to be recommendable only for secondary prevention of stroke, many different specialists may be involved in diagnosis and treatment of the different PFO-related syndromes. When many different professionals are involved in the same patient management, confusion about who does make the diagnosis and who does take decision about medical or interventional therapy would be frequent and correct judgment and actions would be delayed. The authors propose a model of multidisciplinary protocol to manage PFO-related syndrome, in which each specialists has a specific role during the decision-making process that is driven by the cardiologist. PMID- 17355559 TI - Painful legs and moving toes syndrome associated with Hashimoto's disease. AB - A patient with Hashimoto' s disease presented with painful legs and moving toes (PLMT). The neurological and electrophysiological findings suggest that, in this case, PLMT syndrome is a variety of dystonic movement and is associated with Hashimoto's disease. PMID- 17355560 TI - A case of sarcoidosis presenting as a non-specific intramedullary lesion. AB - Neurosarcoidosis occurs in 5-15% of sarcoidosis cases. Approximately 50% of patients with neurosarcoidosis present with a neurological disease at the time sarcoidosis is first diagnosed. Spinal sarcoidosis is rare. We report the case of a 61-year-old man with a highly aspecific intramedullary lesion as the first manifestation of sarcoidosis. One year after the onset of neurological symptoms, the high levels of angiotensin-converting enzyme and the results of a total body gallium scan and bronchoalveolar lavage supported the diagnosis of sarcoidosis. Isolated single reports indicate that spinal neurosarcoidosis may be the initial manifestation of sarcoidosis. In our case, magnetic resonance imaging of the dorsal spine showed a largely aspecific lesion. Neurosarcoidosis should be considered in the differential diagnosis of intramedullary cord lesion with leptomeningeal enhancement; a systematic search for evidence of sarcoidosis should be mandatory in all cases for a correct diagnosis and early treatment. PMID- 17355561 TI - Two cases of Cryptococcus meningitis presenting as leukoencephalopathy prior to amphotericin therapy. AB - We report two patients with cryptococcal meningitis and combined immunodeficiency with unusual magnetic resonance imaging findings of gadolinium-enhancing white matter lesions, quite different from cryptococcomas and seen prior to anti-fungal treatment. The lesions resembled demyelinating plaques and resolved. In one patient, biopsy of the lesion revealed cryptococci, non-specific inflammatory changes and occasional small perivascular lymphocyte collections, but not demyelination. Leukoencephalopathy, previously rarely observed in Cryptococcal meningitis, was thought to be the sequelae of amphotericin toxicity. Our cases demonstrate cryptococcal meningitis may present with leukoencephalopathy, possibly as an immune response to the organism. PMID- 17355562 TI - Interobserver agreement in the magnetic resonance location of cerebral vein and dural sinus thrombosis. AB - The interobserver variation in the magnetic resonance (MR) location of cerebral vein and dural sinus thrombosis (CVT) has not been previously reported. Four independent observers rated a convenience sample of 40 MR/MR angiographies to assess whether or not each dural sinus and major cerebral veins were occluded. Interobserver reliability was measured using kappa statistics. Interobserver agreement was comparable between the six pairs of raters. Agreement was excellent for thrombosis of the deep cerebral venous system (kappa = 1.00), cerebellar veins (kappa = 1.00), superior sagittal sinus (kappa range: 0.82-1) and right jugular vein (kappa range: 0.84-0.95); good to excellent for the right transverse/sigmoid sinus (kappa range: 0.75-0.90) and the left jugular vein (kappa range: 0.65-0.85); moderate to excellent for the left lateral sinus (kappa range: 0.59-0.78) and the straight sinus (kappa range: 0.59-0.92); poor to good for the cortical veins (kappa range: 0.02-0.65). Agreement between observers varies with the location of CVT. It is good or excellent for most of the occluded sinus and veins, except for the cortical veins. This study suggests that information on the location of CVT can be reliably collected and used in multicentre studies. PMID- 17355564 TI - Invasiveness in plant communities with feedbacks. AB - The detrimental effects of invasive plant species on ecosystems are well documented. While much research has focused on discovering ecological influences associated with invasiveness, it remains unclear how these influences interact, causing some introduced exotic species to become invasive threats. Here we develop a framework that incorporates the influences of propagule pressure, frequency independent growth rates, feedback relationships, resource competition and spatial scale of interactions. Our results show that these ecological influences interact in complex ways, resulting in expected outcomes ranging from inability to establish, to naturalization, to conditional invasion dependent on quantity and spatial distribution of propagules, to unconditional takeover. We propose a way to predict the likelihood of these four possible outcomes, for a species recently introduced into a given target community. Such information could enable conservation biologists to craft strategies and target remediation efforts more efficiently and effectively in order to help maintain biodiversity in ecological communities. PMID- 17355565 TI - On quantitative measures of indirect interactions. AB - Indirect effects, whether density-mediated (DMII) or trait-mediated (TMII), have been recognized as potentially important drivers of community dynamics. However, empirical studies that have attempted to detect TMII or to quantify the relative strength of DMII and TMII in short-term studies have used a range of different metrics. We review these studies and assess both the consistency of a variety of different metrics and their robustness to (or ability to detect) ecological phenomena such as the dependence of forager behaviour on conspecific density. Quantifying indirect effects over longer time scales when behaviour and population density vary is more challenging, but also necessary if we really intend to incorporate indirect effects into predictions of long-term community dynamics; we discuss some problems associated with this effort and conclude with general recommendations for quantifying indirect effects. PMID- 17355566 TI - On the experimental evolution of specialization and diversity in heterogeneous environments. AB - Environmental variance can be decomposed into two components: the contrast among patches in the optimal phenotype and the variance in productivity among patches. Both components can influence the outcome of selection in heterogeneous environments. In general genetic diversity within a population should increase as the contrast among patches increases. As the variance in productivity increases, on the other hand, individual niche breadth should decrease since the response to selection becomes dominated by adaptation to the most productive patch. We tested this interpretation of diversity in heterogeneous environments by selecting the bacterium Pseudomonas fluorescens over several hundred generations in pair-wise mixtures of four carbon substrates. We then assessed the response to selection in the mixtures in terms of performance on each component substrate. The results provide general support for this interpretation of the environmental variance and suggest further that competition among genotypes promotes diversification in heterogeneous environments. PMID- 17355567 TI - Plasticity in metabolic allometry: the role of dietary stoichiometry. AB - Metabolism involves multiple elements. While we know much about the allometry in metabolic response of organisms to energy (carbon, C) availability, little is known about how different-sized organisms respond to the relative availability of elements. I experimentally manipulated availability of phosphorus (P) relative to C, to test whether dietary C : P affects metabolism in four species of Daphnia, spanning an order of magnitude in body mass. Results indicated that the slope of the relationship between individual respiration and body mass was M(0.83) under a balanced diet (C : P c. 150), and M(0.67) under an imbalanced diet (C : P c. 800). Increased respiration under dietary imbalance was not due to increased ingestion. The change in the scaling exponent was due to the greater respiratory response of smaller species to altered diets. Diet-induced metabolic plasticity contributes to variation in metabolic allometry, at least at such small scales of body size. PMID- 17355568 TI - Colourful coexistence of red and green picocyanobacteria in lakes and seas. AB - Hutchinson's paradox of the plankton inspired many studies on the mechanisms of species coexistence. Recent laboratory experiments showed that partitioning of white light allows stable coexistence of red and green picocyanobacteria. Here, we investigate to what extent these laboratory findings can be extrapolated to natural waters. We predict from a parameterized competition model that the underwater light colour of lakes and seas provides ample opportunities for coexistence of red and green phytoplankton species. To test this prediction, we sampled picocyanobacteria of 70 aquatic ecosystems, ranging from clear blue oceans to turbid brown peat lakes. As predicted, red picocyanobacteria dominated in clear waters, whereas green picocyanobacteria dominated in turbid waters. We found widespread coexistence of red and green picocyanobacteria in waters of intermediate turbidity. These field data support the hypothesis that niche differentiation along the light spectrum promotes phytoplankton biodiversity, thus providing a colourful solution to the paradox of the plankton. PMID- 17355569 TI - Pollination and other ecosystem services produced by mobile organisms: a conceptual framework for the effects of land-use change. AB - Many ecosystem services are delivered by organisms that depend on habitats that are segregated spatially or temporally from the location where services are provided. Management of mobile organisms contributing to ecosystem services requires consideration not only of the local scale where services are delivered, but also the distribution of resources at the landscape scale, and the foraging ranges and dispersal movements of the mobile agents. We develop a conceptual model for exploring how one such mobile-agent-based ecosystem service (MABES), pollination, is affected by land-use change, and then generalize the model to other MABES. The model includes interactions and feedbacks among policies affecting land use, market forces and the biology of the organisms involved. Animal-mediated pollination contributes to the production of goods of value to humans such as crops; it also bolsters reproduction of wild plants on which other services or service-providing organisms depend. About one-third of crop production depends on animal pollinators, while 60-90% of plant species require an animal pollinator. The sensitivity of mobile organisms to ecological factors that operate across spatial scales makes the services provided by a given community of mobile agents highly contextual. Services vary, depending on the spatial and temporal distribution of resources surrounding the site, and on biotic interactions occurring locally, such as competition among pollinators for resources, and among plants for pollinators. The value of the resulting goods or services may feed back via market-based forces to influence land-use policies, which in turn influence land management practices that alter local habitat conditions and landscape structure. Developing conceptual models for MABES aids in identifying knowledge gaps, determining research priorities, and targeting interventions that can be applied in an adaptive management context. PMID- 17355570 TI - Evolution and the latitudinal diversity gradient: speciation, extinction and biogeography. AB - A latitudinal gradient in biodiversity has existed since before the time of the dinosaurs, yet how and why this gradient arose remains unresolved. Here we review two major hypotheses for the origin of the latitudinal diversity gradient. The time and area hypothesis holds that tropical climates are older and historically larger, allowing more opportunity for diversification. This hypothesis is supported by observations that temperate taxa are often younger than, and nested within, tropical taxa, and that diversity is positively correlated with the age and area of geographical regions. The diversification rate hypothesis holds that tropical regions diversify faster due to higher rates of speciation (caused by increased opportunities for the evolution of reproductive isolation, or faster molecular evolution, or the increased importance of biotic interactions), or due to lower extinction rates. There is phylogenetic evidence for higher rates of diversification in tropical clades, and palaeontological data demonstrate higher rates of origination for tropical taxa, but mixed evidence for latitudinal differences in extinction rates. Studies of latitudinal variation in incipient speciation also suggest faster speciation in the tropics. Distinguishing the roles of history, speciation and extinction in the origin of the latitudinal gradient represents a major challenge to future research. PMID- 17355571 TI - Effects of UVB radiation on marine and freshwater organisms: a synthesis through meta-analysis. AB - Ultraviolet-B (UVB) radiation is a global stressor with potentially far-reaching ecological impacts. In the first quantitative analysis of the effects of UVB on aquatic organisms, we used meta-analytic techniques to explore the effects of UVB on survival and growth in freshwater and marine systems. Based on the large body of literature on the effects of UVB in aquatic systems, we predicted that UVB would have different effects in different habitats, experimental venues, trophic groups and life history stages. Contrary to our predictions, we found an overall negative effect of UVB on both survival and growth that crossed life histories, trophic groups, habitats and experimental venues. UVB had larger negative effects on growth in embryos compared with later life history stages. Despite the overall negative effect of UVB, effect sizes varied widely. In the survival analyses, no relationship between mean effect size and taxonomic groups or levels of exposure to UVB was detected. In the growth analyses, a larger negative effect on protozoans was observed. Our analyses suggest that the effects of UVB in aquatic systems are large and negative but highly variable between organisms. Variation in susceptibility may have important implications for population and community structure. PMID- 17355572 TI - Further characterization of ADAMTS-13 inactivation by thrombin. AB - BACKGROUND: The multimeric size and platelet-tethering function of von Willebrand factor (VWF) are modulated by the plasma metalloprotease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13). In vitro ADAMTS-13 is susceptible to proteolytic inactivation by thrombin. OBJECTIVES: In this study, we aimed to characterize the inactivation of ADAMTS-13 by thrombin and to assess its physiological significance. METHODS AND RESULTS: By N-terminal sequencing of cleavage products, and by mutagenesis, we identified the principal thrombin cleavage sites in ADAMTS-13 as R257 and R1176. Using a library of 76 thrombin mutants, we highlighted the functional importance of exosite I on thrombin in the proteolysis of ADAMTS-13. Proteolysis of ADAMTS-13 by thrombin caused an 8-fold reduction in its affinity for VWF that contributed to its loss of VWF-cleaving function. Intriguingly, thrombin-cleaved ADAMTS-13 both bound and proteolyzed a short recombinant VWF A2 domain substrate (VWF115) normally. Following activation of coagulation in normal plasma, endogenous ADAMTS-13, but not added ADAMTS-13, appeared resistant to coagulation-induced fragmentation. An estimation of the K(m) for ADAMTS-13 proteolysis by thrombin was appreciably higher than the physiological concentration of ADAMTS-13. This was corroborated by the comparatively low affinity of ADAMTS-13 for thrombin (K(D) 95 nM). CONCLUSIONS: Together, our data suggest that ADAMTS-13 is protected from rapid proteolytic inactivation by thrombin in normal plasma. Whether this remains the case under pathological situations involving elevated/sustained generation of thrombin remains unclear. PMID- 17355574 TI - Caution in the interpretation of continuous thrombin generation assays. PMID- 17355577 TI - Emergency departments in crisis: opportunities for research. PMID- 17355578 TI - The importance of population-based performance measures. PMID- 17355579 TI - Beyond our walls: impact of patient and provider coordination across the continuum on outcomes for surgical patients. AB - OBJECTIVES: To investigate patients' experience with coordination of their postsurgical care across multiple settings and the effects on key outcomes. DATA SOURCES: Primary data collected over 18 months from 222 unilateral knee replacement patients at Brigham and Women's Hospital in Boston, MA. STUDY DESIGN: Patients were surveyed about the coordination of their postdischarge care during the 6-week period postdischarge when they received care from rehabilitation facilities and/or home care agencies and follow-up care from the surgeon. DATA COLLECTION: Patients were surveyed before surgery and at 6 and 12 weeks postsurgery. PRINCIPAL FINDINGS: Patient reports highlight problems with coordination across settings and between providers and themselves. These problems, measured at 6 weeks, were associated with greater joint pain, lower functioning, and lower patient satisfaction at 6 weeks after surgery. At 12 weeks after surgery, coordination problems were associated with greater joint pain, but were not associated with functional status. CONCLUSION: Coordination across settings affects patients' clinical outcomes and satisfaction with their care. Although accountable for transfer to the next care setting, providers are neither accountable for nor supported to coordinate across the continuum. Addressing this system problem requires both introducing coordinating mechanisms and also supporting their use through changes in providers' incentives, resources, and time. PMID- 17355580 TI - Impact of the Medicare Short Stay Transfer Policy on patients undergoing major orthopedic surgery. AB - OBJECTIVE: To examine the impact of the Short Stay Transfer Policy (SSTP) on practice patterns. DATA SOURCES: This study uses data from the Centers for Medicare and Medicaid Services Medicare Provider Analysis and Review (MEDPAR) file, Home Health Standard Analytical File, 1999 Provider of Service file, and data from the 2000 United States Census. STUDY DESIGN: An interrupted time-series analysis was used to examine the length of stay (LOS) and probability of "early" discharge to post acute care (PAC). DATA COLLECTION: Separate 100 percent samples of all fee-for-service Medicare recipients undergoing either elective joint replacement (JR) surgery or surgical management of hip fracture (FX) between January 1, 1996 and December 31, 2000 were selected. PRINCIPAL FINDINGS: Prior to implementation of the SSTP. LOS had been falling by 0.37 and 0.30 days per year for JR and FX patients respectively. After implementation of the SSTP, there was an immediate increase in LOS by 0.20 and 0.17 days, respectively. Thereafter, LOS remained flat. The proportion of patients discharged "early" to PAC had been rising by 4.4 and 2.6 percentage points per year for JR and FX patients respectively, to a peak of 28.8 percent and 20.4 percent early PAC utilization in September 1998. Immediately after implementation of the SSTP, there was a 4.3 and 3.0 percentage point drop in utilization of "early" PAC. Thereafter utilization of early PAC increased at a much slower rate (for JR) or remained flat (for FX). There was significant regional variation in the magnitude of response to the policy. CONCLUSION: Implementation of the SSTP reduced the financial incentive to discharge patients early to PAC. This was accomplished primarily through longer LOS without meaningful change in PAC utilization. With the recent expansion of the SSTP to 29 DRGs (representing 34 percent of all discharges), these findings have important implications regarding patient care. PMID- 17355581 TI - Assigning ambulatory patients and their physicians to hospitals: a method for obtaining population-based provider performance measurements. AB - OBJECTIVE: To develop a method for assigning Medicare enrollees and the physicians who serve them to individual hospitals with adequate validity to allow population-based assessments of provider specific costs and quality of care. DATA SOURCES/STUDY SETTING: The study populations consist of a 20 percent sample of Medicare fee-for-service enrollees and all physicians submitting claims for Medicare services from 1998 to 2000. Data were obtained from Medicare claims and enrollment files, Medicare's MPIER file, and from the American Hospital Association Annual Survey. STUDY DESIGN: Cross-sectional analysis of the characteristics of hospitals, their extended medical staffs (EMSs) and the utilization patterns of their assigned Medicare enrollees. DATA COLLECTION METHODS: Medicare enrollees were assigned to their predominant ambulatory physician and then to the hospital where that physician provided inpatient services or where a plurality of that physician's patient panel had medical admissions. Each beneficiary was linked to a physician and a hospital regardless of whether the patient was hospitalized creating Ambulatory Provider Specific Cohorts (APSCs). PRINCIPAL FINDINGS: Ninety-six percent of eligible Medicare enrollees who had an index physician visit in 1998 were assigned to a specific provider. Two-thirds of the medical admissions during a 2-year period occurred at the assigned hospital and two-thirds of evaluation and management services were billed by the assigned hospital's EMS. The empirically derived EMS for hospitals had reasonable face and discriminant validity in terms of number and type of physicians practicing at different sized and type hospitals. Estimates of risk adjusted costs across physician groups in year one are highly predictive of costs in a subsequent year (r=0.87, p<.0001 and weighted kappa=0.65, p<.0001). CONCLUSIONS: Medicare claims data can be used to assign virtually all Medicare enrollees to empirically defined care systems comprised of hospitals and the physicians who practice at these hospitals. Studies of patterns of practice, costs and outcomes of care experienced by these APSCs could complement other methods of monitoring provider performance. PMID- 17355582 TI - Does ambulatory process of care predict health-related quality of life outcomes for patients with chronic disease? AB - OBJECTIVE: The validity of quality of care measurement has important implications for practicing clinicians, their patients, and all involved with health care delivery. We used empirical data from managed care patients enrolled in west coast physician organizations to test the hypothesis that observed changes in health-related quality of life across a 2.5-year window reflecting process of care. DATA SOURCES/STUDY SETTING: Patient self-report data as well as clinically detailed medical record review regarding 963 patients with chronic disease associated with managed care from three west coast states. STUDY DESIGN: Prospective cohort study of change in health-related quality of life scores across 30 months as measured by change in SF-12 physical component scores. DATA COLLECTION/EXTRACTION METHODS: Patient self-report and medical record abstraction. PRINCIPAL FINDINGS: We found a positive relationship between better process scores and higher burden of illness (p<.05). After adjustment for burden of illness, using an instrumental variables approach revealed better process is associated with smaller declines in SF-12 scores across a 30-month observation window (p=.014). The application of the best quartile of process of care to patients currently receiving poor process is associated with a 4.24 increment in delta SF-12-physical component summary scores. CONCLUSIONS: The use of instrumental variables allowed us to demonstrate a significant relationship between better ambulatory process of care and better health-related quality of life. This finding underscores the importance of efforts to improve the process of care. PMID- 17355583 TI - Clinical practice guideline implementation strategy patterns in Veterans Affairs primary care clinics. AB - BACKGROUND: The Department of Veterans Affairs (VA) mandated the system-wide implementation of clinical practice guidelines (CPGs) in the mid-1990s, arming all facilities with basic resources to facilitate implementation; despite this resource allocation, significant variability still exists across VA facilities in implementation success. OBJECTIVE: This study compares CPG implementation strategy patterns used by high and low performing primary care clinics in the VA. RESEARCH DESIGN: Descriptive, cross-sectional study of a purposeful sample of six Veterans Affairs Medical Centers (VAMCs) with high and low performance on six CPGs. SUBJECTS: One hundred and two employees (management, quality improvement, clinic personnel) involved with guideline implementation at each VAMC primary care clinic. MEASURES; Participants reported specific strategies used by their facility to implement guidelines in 1-hour semi-structured interviews. Facilities were classified as high or low performers based on their guideline adherence scores calculated through independently conducted chart reviews. FINDINGS: High performing facilities (HPFs) (a) invested significantly in the implementation of the electronic medical record and locally adapting it to provider needs, (b) invested dedicated resources to guideline-related initiatives, and (c) exhibited a clear direction in their strategy choices. Low performing facilities exhibited (a) earlier stages of development for their electronic medical record, (b) reliance on preexisting resources for guideline implementation, with little local adaptation, and (c) no clear direction in their strategy choices. CONCLUSION: A multifaceted, yet targeted, strategic approach to guideline implementation emphasizing dedicated resources and local adaptation may result in more successful implementation and higher guideline adherence than relying on standardized resources and taxing preexisting channels. PMID- 17355584 TI - Does type of gatekeeping model affect access to outpatient specialty mental health services? AB - OBJECTIVE: To measure how a change in gatekeeping model affects utilization of specialty mental health services. DATA SOURCES/STUDY SETTING: Secondary data from health insurance claims for services during 1996-1999. The setting is a managed care organization that changed gatekeeping model in one of its divisions, from in person evaluation to the use of a call-center. STUDY DESIGN: We evaluate the impact of the change in gatekeeping model by comparing utilization during the 2 years before and 2 years after the change, both in the affected division and in another division where gatekeeping model did not change. The design is thus a controlled quasi-experimental one. Subjects were not randomized. Key dependent variables are whether each individual had any specialty mental health visits in a year; the number of visits; and the proportion of users exceeding eight visits in a year. Key explanatory variables include demographic variables and indicators for patient diagnoses and their intervention status (time-period, study group). DATA COLLECTION/EXTRACTION METHODS: Claims data were aggregated to create analytic files with one record per member per year, with variables reporting demographic characteristics and mental health service use. PRINCIPAL FINDINGS: After controlling for secular trends at the other division, the division which changed gatekeeping model eventually experienced an increase in the proportion of enrollees receiving specialty mental health treatment, of 0.5 percentage point. Similarly, there was an increase of about 0.6 annual visits per user, concentrated at the low end of the distribution. These changes occurred only in the second year after the gatekeeping changes. CONCLUSIONS: The results of this study suggest that the gatekeeping changes did lead to increases in utilization of mental health care, as hypothesized. At the same time, the magnitude of the increase in access and mean number of visits that we found was relatively modest. This suggests that while the change from face-to-face specialty gatekeeping to call-center intake does increase utilization, it is unlikely to overwhelm a system with new demand or create huge cost increases. PMID- 17355585 TI - Effect of Medicaid Managed Care on racial disparities in health care access. AB - OBJECTIVE: To evaluate the impact of Medicaid Managed Care (MMC) on racial disparities in access to care consistent with the Institute of Medicine (IOM) definition of racial disparity, which excludes differences stemming from health status but includes socioeconomic status (SES)-mediated differences. DATA SOURCES: Secondary data from the Adult Samples of the 1997-2001 National Health Interview Survey, metropolitan statistical area (MSA)-level Medicaid Health Maintenance Organization (MHMO) market share from the 1997 to 2001 InterStudy MSA Trend Dataset, and MSA characteristics from the 1997 to 2001 Area Resource File. STUDY DESIGN: I estimate multivariate regression models to compare racial disparities in doctor visits, emergency room (ER) use, and having a usual source of care between enrollees in MMC and Medicaid Fee-for-Service (FFS) plans. To contend with potential selection bias, I use a difference-in-difference analytical strategy and assess the impact of greater MHMO market share at the MSA level on Medicaid enrollees' access measures. To implement the IOM definition of racial disparity, I adjust for health status but not SES factors using a novel method to transform the distribution of health status for minority populations to approximate the white health status distribution. PRINCIPAL FINDINGS: MMC enrollment is associated with lowered disparities in having any doctor visit in the last year for blacks, and in having any usual source of care for both blacks and Hispanics. Increasing Medicaid HMO market share lowered disparities in having any doctor visits in the last year for both blacks and Hispanics. Although disparities in most other measures were not much affected, black-white ER use disparities exist among MMC enrollees and in areas of high MHMO market share. CONCLUSIONS: MMC programs' reduction of some disparities suggests that recent shifts in Medicaid policy toward managed care plans have benefited minority enrollees. Future research should investigate whether black-white disparities in ER use within MMC groups represent the flexibility of MMC plans to locate primary care in ERs or an inefficient delivery of care. PMID- 17355586 TI - Analyzing multiple informant data from an evaluation of the health disparities collaboratives. AB - OBJECTIVE: To use multivariate regression methods to analyze simultaneously data obtained from multiple respondents or data sources (informants) at health centers. DATA SOURCE: Surveys of executive directors, medical directors, and providers from 65 community health centers (176 informants) who participated in an evaluation of the Health Disparities Collaboratives. STUDY DESIGN: Cross sectional survey of staff at the health centers during 2003-2004. STATISTICAL METHODS: In order to illustrate this method, we analyze the association between informants' assessments of the culture of the center and participation in the collaborative, and the association between computer availability and the effort made by management to improve the quality of the care and services at their center. Multivariate regression models are used to pool information across informants while accounting for informant-specific effects and retaining informants in the analysis even if the data from some of them are missing. The results are compared with those obtained by traditional methods that use data from a single informant or average over informants' ratings. FINDINGS: In both the Collaborative participation and quality improvement efforts analyses, the multivariate regression multiple informants' analysis found significant effects and differences between informants that traditional methods failed to find. Participating centers emphasized developmental (entrepreneurship, innovation, risk-taking) and rational culture. The effect of hierarchical culture (stability and bureaucracy) on participation depended on the informant; executive directors and medical providers were the most discrepant. In centers that participated in the Collaborative, the availability of computers was positively associated with the effort that management made toward improving quality. CONCLUSIONS: The multiple informants model provided the most precise estimates and alerts users to differential effects across informants. Because different informants may have different insights or experiences, it is important that differences among informants be measured and ultimately understood by health services researchers. PMID- 17355587 TI - Treatment for ADHD: is more complex treatment cost-effective for more complex cases? AB - OBJECTIVE: To determine the cost-effectiveness of three alternative high-quality treatments for attention deficit hyperactivity disorder (ADHD) relative to community care (CC) and to determine whether cost-effectiveness varies with the presence of comorbid disorders. DATA SOURCES/COLLECTION: The study included 579 children ages 7-9.9 with diagnosed ADHD at six sites. Data for the study were distilled from administrative data and from interviews with parents, including estimates of the child's functional impairment. These analyses focus on changes in functional impairment over 14 months. STUDY DESIGN: The study involved a large clinical trial that randomized participants to one of four arms: routine CC, intensive medication management (MedMgt), multicomponent behavioral treatment, and a combination of behavioral treatment and medication. PRINCIPAL FINDINGS: We assessed the cost-effectiveness of the alternatives using costs measured from a payer perspective. The preferred cost-effective treatment varies as a function of the child's comorbidity and of the policy maker's willingness to pay. For pure (no comorbidity) ADHD, high-quality MedMgt appears likely to be cost-effective at all levels of willingness to pay. In contrast, for some comorbid conditions, willingness to pay is critical: the policy maker with low willingness to pay likely will judge MedMgt most cost-effective. On the other hand, a policy maker willing to pay more now in expectation of future costs savings (involving, for example, juvenile justice), will recognize that the most cost-effective choice for comorbid conditions likely involves behavior therapy, with or without medication. CONCLUSIONS: Analyses of costs and effectiveness of treatment for ADHD must consider the role of comorbidities. PMID- 17355588 TI - Use of aggressive medical treatments near the end of life: differences between patients with and without dementia. AB - OBJECTIVE: To analyze whether acute care patients with dementia are more or less likely to receive each of five aggressive medical services near the end of life, compared with patients without dementia. DATA SOURCES: Two years of Veterans Affairs (VA) and Medicare utilization data for all 169,036 VA users nationwide age 67 and older who died between October 1, 1999 and September 30, 2001. STUDY DESIGN: We performed a retrospective analysis of acute care stays discharged in the final 30 days of life. The main outcome measure was the patient's likelihood of receiving each of five aggressive services (intensive care unit [ICU] admission, ventilator, cardiac catheterization, pulmonary artery monitor, and dialysis), controlling for demographic and clinical factors in probit regressions. PRINCIPAL FINDINGS: There were 122,740 acute-stay discharges during the final 30 days of life, representing 94,100 unique patients (31,654 with dementia). In probit models comparing acute care patients with and without dementia, patients with dementia were 7.5 percentage points less likely to be admitted to the ICU (95 percent confidence interval [CI], 6.9-8.1; percent of stays with ICU admission=36.8 percent), 5.4 percentage points less likely to be placed on a ventilator (95 percent CI, 5.0-5.9; percent of stays with ventilator use=17.1 percent), 0.7 percentage points less likely to receive cardiac catheterization (95 percent CI, 0.6-0.8; percent of stays with cardiac catheterization=2.7 percent), 1.4 percentage points less likely to receive pulmonary artery monitoring (95 percent CI, 1.2-1.5; percent of stays with pulmonary artery monitoring=2.6 percent), and 0.6 percentage points less likely to receive dialysis (95 percent CI, 0.4-0.8; percent of stays with dialysis=4.6 percent). CONCLUSIONS: During the final 30 days of life, acute care patients with dementia are treated substantially less aggressively than patients without dementia. Further research is warranted to determine the causes and appropriateness of these patterns of care. PMID- 17355589 TI - The boomers are coming: a total cost of care model of the impact of population aging on health care costs in the United States by Major Practice Category. AB - OBJECTIVE: To project the impact of population aging on total U.S. health care per capita costs from 2000 to 2050 and for the range of clinical areas defined by Major Practice Categories (MPCs). DATA SOURCES: Secondary data: HealthPartners health plan administrative data; U.S. Census Bureau population projections 2000 2050; and MEPS 2001 health care annual per capita costs. STUDY DESIGN: We calculate MPC-specific age and gender per capita cost rates using cross-sectional data for 2002-2003 and project U.S. changes by MPC due to aging from 2000 to 2050. DATA COLLECTION METHODS: HealthPartners data were grouped using purchased software. We developed and validated a method to include pharmacy costs for the uncovered. PRINCIPAL FINDINGS: While total U.S. per capita costs due to aging from 2000 to 2050 are projected to increase 18 percent (0.3 percent annually), the impact by MPC ranges from a 55 percent increase in kidney disorders to a 12 percent decrease in pregnancy and infertility care. Over 80 percent of the increase in total per capita cost will result from just seven of the 22 total MPCs. CONCLUSIONS: Understanding the differential impact of aging on costs at clinically specific levels is important for resource planning, to effectively address future medical needs of the aging U.S. population. PMID- 17355590 TI - Revisiting the relationship between managed care and hospital consolidation. AB - OBJECTIVE: This paper analyzes whether the rise in managed care during the 1990s caused the increase in hospital concentration. DATA SOURCES: We assemble data from the American Hospital Association, InterStudy and government censuses from 1990 to 2000. STUDY DESIGN: We employ linear regression analyses on long differenced data to estimate the impact of managed care penetration on hospital consolidation. Instrumental variable analogs of these regressions are also analyzed to control for potential endogeneity. DATA COLLECTION: All data are from secondary sources merged at the level of the Health Care Services Area. PRINCIPLE FINDINGS: In 1990, the mean population-weighted hospital Herfindahl-Hirschman index (HHI) in a Health Services Area was .19. By 2000, the HHI had risen to .26. Most of this increase in hospital concentration is due to hospital consolidation. Over the same time frame HMO penetration increased three fold. However, our regression analysis strongly implies that the rise of managed care did not cause the hospital consolidation wave. This finding is robust to a number of different specifications. PMID- 17355592 TI - Identifying affordable sources of medical care among uninsured persons. AB - OBJECTIVE: To examine the effects of policy, health system, and sociodemographic characteristics on the likelihood that uninsured persons pay a lower price at their regular source of care, or that they are aware of lower priced providers in their community. DATA SOURCES: The 2003 Community Tracking Study household survey, a nationally representative sample of the U.S. population and 60 randomly selected communities. STUDY DESIGN: The survey asked uninsured persons if they paid full or reduced cost at their usual source of medical care, or if they were aware of providers in their community that charge less for uninsured people. We use binomial and multinomial logistic regression analysis to examine the effects of various policy, health system, and sociodemographic characteristics on use and awareness of lower priced providers. We focus especially on the effects of safety net capacity, measured by safety-net hospitals, community health centers, physicians' charity care, and Community Access Program (CAP) grants. PRINCIPAL FINDINGS: Less than half of the uninsured (47.5 percent) reported that they used or were aware of a lower priced provider in their community. Multivariate regression analysis shows that greater safety-net capacity is associated with a higher likelihood of having a lower priced provider as the regular source of care and greater awareness of lower priced providers. Lower incomes and racial/ethnic minorities also had a higher likelihood of having a lower priced provider, although health status did not have statistically significant effects. CONCLUSION: Although increased safety-net capacity may lead to more uninsured having a lower priced provider, many uninsured who live near safety-net providers are not aware of their presence. Greater outreach designed to increase awareness may be needed in order to increase the effectiveness of safety-net providers in improving access to care for the uninsured. PMID- 17355593 TI - Immigrants and employer-sponsored health insurance. AB - OBJECTIVE: To investigate the factors underlying the lower rate of employer sponsored health insurance coverage for foreign-born workers. DATA SOURCES: 2001 Survey of Income and Program Participation. STUDY DESIGN: We estimate probit regressions to determine the effect of immigrant status on employer-sponsored health insurance coverage, including the probabilities of working for a firm that offers coverage, being eligible for coverage, and taking up coverage. DATA EXTRACTION METHODS: We identified native born citizens, naturalized citizens, and noncitizen residents between the ages of 18 and 65, in the year 2002. PRINCIPAL FINDINGS: First, we find that the large difference in coverage rates for immigrants and native-born Americans is driven by the very low rates of coverage for noncitizen immigrants. Differences between native-born and naturalized citizens are quite small and for some outcomes are statistically insignificant when we control for observable characteristics. Second, our results indicate that the gap between natives and noncitizens is explained mainly by differences in the probability of working for a firm that offers insurance. Conditional on working for such a firm, noncitizens are only slightly less likely to be eligible for coverage and, when eligible, are only slightly less likely to take up coverage. Third, roughly two-thirds of the native/noncitizen gap in coverage overall and in the probability of working for an insurance-providing employer is explained by characteristics of the individual and differences in the types of jobs they hold. CONCLUSIONS: The substantially higher rate of uninsurance among immigrants is driven by the lower rate of health insurance offers by the employers of immigrants. PMID- 17355594 TI - Preparing and presenting effective research posters. AB - OBJECTIVES: Posters are a common way to present results of a statistical analysis, program evaluation, or other project at professional conferences. Often, researchers fail to recognize the unique nature of the format, which is a hybrid of a published paper and an oral presentation. This methods note demonstrates how to design research posters to convey study objectives, methods, findings, and implications effectively to varied professional audiences. METHODS: A review of existing literature on research communication and poster design is used to identify and demonstrate important considerations for poster content and layout. Guidelines on how to write about statistical methods, results, and statistical significance are illustrated with samples of ineffective writing annotated to point out weaknesses, accompanied by concrete examples and explanations of improved presentation. A comparison of the content and format of papers, speeches, and posters is also provided. FINDINGS: Each component of a research poster about a quantitative analysis should be adapted to the audience and format, with complex statistical results translated into simplified charts, tables, and bulleted text to convey findings as part of a clear, focused story line. CONCLUSIONS: Effective research posters should be designed around two or three key findings with accompanying handouts and narrative description to supply additional technical detail and encourage dialog with poster viewers. PMID- 17355591 TI - Health care markets, the safety net, and utilization of care among the uninsured. AB - OBJECTIVE: To quantify the relationship between utilization of care among the uninsured and the structure of the local health care market and safety net. DATA SOURCES/STUDY SETTING: Nationally representative data from the 1996 to 2000 waves of the Medical Expenditure Panel Survey (MEPS) linked to data from multiple secondary sources. STUDY DESIGN: We separately analyze outpatient care utilization and whether an individual incurred any medical expenditure among uninsured adults living in urban and rural areas. Safety net measures include distances between each individual and the nearest safety net providers as well as a measure of capacity based on local government and hospital health expenditures. Other covariates include the managed care presence in the local health care market, the percentage of individuals who are uninsured in the area, and local primary care physician supply. We simulate utilization using standardized predictions. PRINCIPAL FINDINGS: Distances between the rural uninsured and safety net providers are significantly associated with utilization. In urban areas, we find that the percentage of individuals in the area who are uninsured, the pervasiveness and competitiveness of managed care, the primary care physician supply, and safety net capacity have a significant relationship with health care utilization. CONCLUSIONS: Facilitating transport to safety net providers and increasing the number of such providers are likely to increase utilization of care among the rural uninsured. Our findings for urban areas suggest that the uninsured living in areas where managed care presence is substantial, and especially where managed care competition is limited, could be a target for policies to improve the ability of the uninsured to obtain care. Policies oriented toward enhancing funding for the safety net and increasing the capacity of safety net providers are likely to be important to ensuring the urban uninsured are able to obtain health care. PMID- 17355595 TI - Defining interdisciplinary research: conclusions from a critical review of the literature. AB - OBJECTIVE: To summarize findings from a systematic exploration of existing literature and views regarding interdisciplinarity, to discuss themes and components of such work, and to propose a theoretically based definition of interdisciplinary research. DATA SOURCES/STUDY SETTING: Two major data sources were used: interviews with researchers from various disciplines, and a systematic review of the education, business, and health care literature from January 1980 through January 2005. STUDY DESIGN: Systematic review of literature, one-on-one interviews, field test (survey). DATA COLLECTION/EXTRACTION METHODS: We reviewed 14 definitions of interdisciplinarity, the characteristics of 42 interdisciplinary research publications from multiple fields of study, and 14 researcher interviews to arrive at a preliminary definition of interdisciplinary research. That definition was then field tested by 12 individuals with interdisciplinary research experience, and their responses incorporated into the definition of interdisciplinary research proposed in this paper. PRINCIPAL FINDINGS: Three key definitional characteristics were identified: the qualitative mode of research (and its theoretical underpinnings), existence of a continuum of synthesis among disciplines, and the desired outcome of the interdisciplinary research. CONCLUSION: Existing literature from several fields did not provide a definition for interdisciplinary research of sufficient specificity to facilitate activities such as identification of the competencies, structure, and resources needed for health care and health policy research. This analysis led to the proposed definition, which is designed to aid decision makers in funding agencies/program committees and researchers to identify and take full advantage the interdisciplinary approach, and to serve as a basis for competency-based formalized training to provide researchers with interdisciplinary skills. PMID- 17355596 TI - Enhancement of fludioxonil fungicidal activity by disrupting cellular glutathione homeostasis with 2,5-dihydroxybenzoic acid. AB - The activity of fludioxonil, a phenylpyrrole fungicide, is elevated by coapplication of the aspirin/salicylic acid metabolite, 2,5-dihydroxybenzoic acid (2,5-DHBA). Fludioxonil activity is potentiated through a mitogen-activated protein kinase (MAPK) pathway that regulates osmotic/oxidative stress-responses. 2,5-DHBA disrupts cellular GSH (reduced glutathione)/GSSG (oxidized glutathione) homeostasis, further stressing the oxidative stress-response system. This stress enhances fludioxonil activity. 2,5-DHBA treatment also prevents tolerance of MAPK mutants resistant to fludioxonil. PMID- 17355597 TI - Quorum-sensing signaling is required for production of the antibiotic pyrrolnitrin in a rhizospheric biocontrol strain of Serratia plymuthica. AB - One mechanism that bacteria have adopted to regulate the production of antimicrobial compounds is population-density-dependent LuxRI-type quorum sensing (QS), exploiting the production of N-acyl homoserine lactone (AHL) autoinducer signals. In biocontrol bacteria, most known cases involve the AHL control of phenazine antibiotics production by rhizospheric pseudomonads. This work is the first to demonstrate that phenazines are not the only group of biocontrol-related antibiotics whose production is regulated by QS systems. Strain HRO-C48 of Serratia plymuthica isolated from the rhizosphere of oilseed rape and described as a chitinolytic bacterium, which protects crops against Verticillium wilt, was also shown to produce wide-range antibiotic pyrrolnitrin and several AHLs, including N-butanoyl-HSL, N-hexanoyl-HSL and N-3-oxo-hexanoyl-HSL (OHHL). The genes splI and splR, which are analogues of luxI and luxR genes from other Gram negative bacteria, were cloned and sequenced. The mutant AHL-4 (splI::miniTn5) was simultaneously deficient in the production of AHLs and pyrrolnitrin, as well as in its ability to suppress the growth of several fungal plant pathogens in vitro. However, pyrrolnitrin production could be restored in this mutant by introduction of the splIR genes cloned into a plasmid or by addition of the conditioned medium from strain C48 or OHHL standard to the growth medium. PMID- 17355598 TI - Impact of nutritional supplements and monosaccharides on growth, oxalate accumulation, and culture pH by Sclerotinia sclerotiorum. AB - Sclerotinia sclerotiorum D-E7 was studied to determine the impact of nutritional supplements and monosaccharides on growth, oxalate accumulation, and culture pH in broth media (initial pH c. 5). Cultures with 0.1% nutritional supplement (tryptone, yeast extract, or soytone) yielded minimal growth, 2-3 mM oxalate, and a final culture pH of 4.2-4.8. In contrast, cultures with 0.1% nutritional supplement and 25 mM glucose yielded significant growth, minimal oxalate (<1 mM), and a final culture pH of 2.8-3.7. Similar trends were observed when glucose in 0.1% soytone cultures was replaced with 25 mM d-mannose, l-arabinose, or d xylose. With 1% soytone-25 mM glucose cultures, growth and oxalate accumulation ( approximately 21 mM) occurred with little change in initial pH. This was not the case with 1% soytone-250 mM glucose cultures; increased glucose levels resulted in a decrease in oxalate accumulation ( approximately 7 mM) and in final culture pH (3.4). Time-course studies with these cultures revealed that oxalate accumulation was suppressed during growth when the culture pH dropped to <4. Overall, these results indicate that (1) the decrease in external pH (i.e. acidification) was independent of oxalate accumulation and (2) acidification coupled to glucose-dependent growth regulated oxalate accumulation by Sclerotinia sclerotiorum. PMID- 17355599 TI - The genetic background of Streptococcus pneumoniae affects protection in mice immunized with PspA. AB - Anti-PspA antibodies are less efficient at protecting mice against certain pneumococcal strains. Immunization with PspA from EF5668 provided better protection against WU2 (a different capsular serotype and PspA family) than against EF5668. To understand the role of the pneumococcal genetic background in anti-PspA-mediated protection, we constructed a mutant of WU2 expressing pspA from EF5668. Both passive and active immunization demonstrated that the genetic background impacted the protection mediated by anti-PspA antibodies. We localized the protection-eliciting region to the first 122 amino acid residues of the N terminus of the alpha-helical domain of PspA/EF5668. PMID- 17355600 TI - 13C-Labeled metabolic flux analysis of a fed-batch culture of elutriated Saccharomyces cerevisiae. AB - This study addresses the question of whether observable changes in fluxes in the primary carbon metabolism of Saccharomyces cerevisiae occur between the different phases of the cell division cycle. To detect such changes by metabolic flux analysis, a 13C-labeling experiment was performed with a fed-batch culture inoculated with a partially synchronized cell population obtained through centrifugal elutriation. Such a culture exhibits dynamic changes in the fractions of cells in different cell cycle phases over time. The mass isotopomer distributions of free intracellular metabolites in central carbon metabolism were measured by liquid chromatography-mass spectrometry. For four time points during the culture, these distributions were used to obtain the best estimates for the metabolic fluxes. The obtained flux fits suggested that the optimally fitted split ratio for the pentose phosphate pathway changed by almost a factor of 2 up and down around a value of 0.27 during the experiment. Statistical analysis revealed that some of the fitted flux distributions for different time points were significantly different from each other, indicating that cell cycle dependent variations in cytosolic metabolic fluxes indeed occurred. PMID- 17355601 TI - Variability in occurrence of multiple prophage genes in Salmonella Typhimurium strains isolated in Slovak Republic. AB - Lysogenic bacteriophages are a significant source of variability in closely related Salmonella strains. In this study, screening for diversity of 152 Salmonella Typhimurium strains was performed using PCR detection of selected prophage regions derived from phages P22, Gifsy-1, Gifsy-2, Fels-1, ST104 and SopEPhi. A high degree of variability was observed in the presence of specific genes. Based on the presence of particular prophage genes, we divided strains into 37 different PCR-prophage profiles; 20 of them were represented by only a single strain. Using multilocus variable number tandem repeats analysis (MLVA), 152 Salmonella strains were separated into 82 MLVA strings. Similar grouping of Salmonella strains was observed in the case of PCR-prophage detection and MLVA and the results corresponded well with the phage type of strains. However, several Salmonella strains were detected, which were closely related according to MLVA; yet, they differed in PCR phage profiles. The observations support a view that integration/excision of bacteriophages in Salmonella strains are frequent events shaping the bacterial genome. PMID- 17355603 TI - Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs. AB - OBJECTIVES: Investigation of the efficacy of zonisamide as an add-on therapy in dogs with refractory epilepsy. METHODS: Thirteen dogs fulfilled the inclusion criteria of poor seizure control despite adequate serum levels of phenobarbital, potassium bromide or both. One further dog was treated with zonisamide as monotherapy because of severe blood dyscrasia due to phenobarbital treatment. Various seizure parameters were evaluated retrospectively for a four month period without zonisamide and prospectively for the same time period under zonisamide add-on therapy. The study time period was extended by up to 17 months to evaluate long-term outcome. RESULTS: Data of 11 dogs could be evaluated: nine of them were responders. The median reduction of seizure frequency of all dogs on zonisamide add-on therapy was 70 per cent (range 14 to 100 per cent). Only transient central nervous system side effects were reported. No further increase of liver enzymes occurred. In three of the responder dogs, seizure control subsided after individual time periods (between 69 days and seven months). CLINICAL SIGNIFICANCE: In dogs with refractory epilepsy, zonisamide may have a beneficial effect on seizure control. In three responder dogs, seizure activity relapsed possibly because of an induction of tolerance. Limiting factors are the high costs. PMID- 17355605 TI - Diagnosing appendicular osteosarcoma with ultrasound-guided fine-needle aspiration: 36 cases. AB - OBJECTIVES: To determine the ability to obtain diagnostic cytology samples from appendicular bone lesions using ultrasound-guided needle aspirations. Secondary objectives were to compare cytological evaluations with histopathological results and to determine the utility of staining malignant mesenchymal cells for the presence of alkaline phosphatase. METHODS: Aspirations from 36 aggressive appendicular bone lesions with histological diagnoses were included in the study. Ultrasound was used to guide the needle to the medullary cavity or the adjacent soft tissue mass. The smears stained with Wright-Giemsa and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indoyl phosphate toluidine salt (NBT/BCIP) were examined. RESULTS: A diagnostic sample was obtained in 32 of the 36 cases. Of the 32 diagnostic samples, cytology indicated sarcoma, with a sensitivity of 97 per cent (confidence interval: 83 to 100 per cent) and a specificity of 100 per cent (confidence interval: 16 to 100 per cent). When a diagnosis of sarcoma was made on cytology, alkaline phosphatase staining indicated osteosarcoma, with a sensitivity of 100 per cent (confidence interval: 87 to 100 per cent). CLINICAL SIGNIFICANCE: The results of this study indicate that ultrasound-guided needle aspiration of aggressive bone lesions is a viable technique for identifying malignant mesenchymal cells and for diagnosing sarcomas. It is cost-effective and minimally invasive. Furthermore, identifying alkaline-phosphatase-negative malignant mesenchymal cells from a bone aspiration may rule out osteosarcoma, whereas alkaline-phosphatase-positive malignant mesenchymal cells are suggestive of osteosarcoma. PMID- 17355604 TI - Efficacy and safety of cefovecin (Convenia) for the treatment of urinary tract infections in dogs. AB - OBJECTIVES: To determine the efficacy and safety of cefovecin (Convenia); Pfizer Animal Health) in the treatment of urinary tract infections in dogs. METHODS: A multi-centre, blinded, randomised study was conducted in 129 dogs with urinary tract infections. Cephalexin (Rilexine) administered twice daily at 15 mg/kg bodyweight orally for 14 days was compared with a single, subcutaneous injection of cefovecin (Convenia) in dogs. The primary efficacy parameter assessed was bacterial elimination of the pretreatment uropathogen. RESULTS: One hundred and twenty-nine dogs were included in efficacy assessments. Escherichia coli was eliminated in 90.5 per cent of cefovecin-treated dogs compared with 52.9 per cent of cephalexin-treated dogs (P=0.0004). Overall cure rates for dogs with Escherichia coli infections were 79.1 per cent for cefovecin and 36.4 per cent for cephalexin-treated dogs (P=0.0003). There were no suspected adverse drug reactions attributed to treatment with cefovecin or cephalexin. CLINICAL SIGNIFICANCE: Cefovecin was shown to be an effective and safe treatment for urinary tract infections. PMID- 17355606 TI - Improved survival in a retrospective cohort of 28 dogs with insulinoma. AB - OBJECTIVES: To determine the survival times for a cohort of dogs with insulinoma and to describe the impact of medical therapy both in non-surgical cases and in surgical cases following relapse. METHODS: A retrospective study of dogs with insulinoma is presented. The Kaplan-Meier method is used to evaluate the survival characteristics of this population. RESULTS: Twenty-eight dogs were included in the study. The median survival time for all dogs was 547 days. Nineteen patients underwent partial pancreatectomy. The median survival time for this group was 785 days and for those subsequently receiving prednisolone therapy on relapse it was 1316 days. Perioperative complications are discussed. CLINICAL SIGNIFICANCE: Survival times in this study exceed those in other studies published previously. In part, this is explained by an improved remission duration following surgery compared with previous reports. More striking though is the longevity of patients following institution of medical therapy. These data give strong objective support to the role of medical therapy in the management of canine insulinoma, including following relapse after surgically induced remission. PMID- 17355607 TI - Treatment of tibial fractures with plates using minimally invasive percutaneous osteosynthesis in dogs and cats. AB - OBJECTIVES: The aim of the here described case series was to develop and evaluate the minimally invasive percutaneous osteosynthesis for the plate fixation of tibial fractures in dogs and cats. METHODS: Six dogs and four cats with shaft fractures of the tibia were treated using minimally invasive percutaneous osteosynthesis. Follow-up radiographs four to six weeks after fracture fixation were evaluated for fracture healing. For the long-term follow-up (minimum 2.4 years), owners were contacted by phone to complete a questionnaire. RESULTS: All fractures healed without the need for a second procedure. Follow-up radiographs obtained after four to six weeks in seven cases showed advanced bony healing with callus formation and filling of the fracture gaps with calcified tissue in all seven. All the patients had a good to excellent long-term result with full limb function. The time needed for regaining full limb use was two to three months. CLINICAL SIGNIFICANCE: Minimally invasive percutaneous osteosynthesis seems to be a useful technique for the treatment of tibial shaft fractures in dogs and cats. PMID- 17355608 TI - Focal metatarsal sinus tracts in a Weimaraner successfully managed with ciclosporin. AB - Focal metatarsal sinus tracts ('fistulation') are, to the authors knowledge, reported for the first time in a Weimaraner. The six-year-old, entire male had a five-month history of two symmetrical, well-demarcated sinuses on the plantar aspect of each metatarsus. The area surrounding each pair of sinuses was slightly fluctuant and a serosanguineous discharge could be expressed. Cytological examination of the discharge was characteristic of pyogranulomatous inflammation. Bacterial culture showed the material to be sterile. Examination of a skin biopsy revealed a severe inflammatory reaction involving the dermal collagen, with an infiltrate of neutrophils, macrophages, lymphocytes, plasma cells and multi nucleated giant cells, with some micro-pustule formation. Treatment with ciclosporin induced total remission. Reduction of the dose of ciclosporin resulted in recurrence of the physical signs with further remission on re introduction of the original dosage. This is the first report of the use of ciclosporin to control this condition. PMID- 17355609 TI - Generalised lymphadenomegaly associated with methimazole treatment in a hyperthyroid cat. AB - A nine-year-old, domestic shorthair cat was diagnosed with hyperthyroidism and treated with methimazole, which resulted in lethargy, inappetence and marked generalised lymphadenomegaly within two weeks of initiation of therapy. Cytology, histopathology and immunohistochemistry were suggestive of atypical lymphoid hyperplasia. Cessation of treatment resulted in resolution of all clinical signs and physical abnormalities within two days. Subsequent treatment with radioactive iodine cured this cat of its hyperthyroidism. The lymphadenomegaly did not return at any stage and the cat is currently asymptomatic. Although methimazole administration for feline hyperthyroidism has been associated with many side effects, lymphadenomegaly has, to the authors' knowledge, not been previously reported. PMID- 17355610 TI - Excision arthroplasty of the interphalangeal joint as an alternative to digit amputation in two dogs. AB - Excision arthroplasty of the interphalangeal joint was used as an alternative to digit amputation for comminuted fractures of the phalangeal bones in two dogs. Both patients had return of pain-free use of the affected limb, even though both weight-bearing digits were involved in one case. This type of surgery might prove to be superior to the more invasive digit amputation, salvaging the digits and providing a better functional outcome. PMID- 17355611 TI - Possible pseudogout in two dogs. AB - Pseudogout, the acute form of calcium pyrophosphate deposition disease, is a common condition in elderly human beings and is characterised by the sudden onset of intense joint pain and synovitis. It is rarely identified in animals but was diagnosed in two dogs that presented with acute lameness and pyrexia. Cytology of the synovial fluid showed a mildly elevated cell count with both non-degenerate neutrophils and mononuclear cells present. Many of the mononuclear cells and occasional neutrophils contained square or rhomboid-shaped crystals that were variable in shape and size and weakly birefringent on examination under polarised light. Clinical signs resolved following treatment with prednisolone. PMID- 17355613 TI - What is your diagnosis? Large air-way neoplasia (undifferentiated sarcoma) resulting in obstruction of the distal trachea. PMID- 17355614 TI - Urethral prolapse in three male Yorkshire terriers. PMID- 17355615 TI - Dermoid sinus and bone defects of the fifth thoracic vertebrae in a shih-tzu. PMID- 17355616 TI - Visceral mast cell tumour in a dog with haemabdomen and mastocytaemia. PMID- 17355617 TI - Management of children's urinary tract infections in Dutch family practice: a cohort study. AB - BACKGROUND: Optimal clinical management of childhood urinary tract infections (UTI) potentiates long-term positive health effects. Insight into the quality of care in Dutch family practices for UTIs was limited, particularly regarding observation periods of more than a year. Our aim was to describe the clinical management of young children's UTIs in Dutch primary care and to compare this to the national guideline recommendations. METHODS: In this cohort study, all 0 to 6 year-old children with a diagnosed UTI in 2001 were identified within the Netherlands Information Network of General Practitioners (LINH), which comprises 120 practices. From the Dutch guideline on urinary tract infections, seven indicators were derived, on prescription, follow-up, and referral. RESULTS: Of the 284 children with UTI who could be followed for three years, 183 (64%) were registered to have had one cystitis episode, 52 (18%) had two episodes, and 43 (15%) had three or more episodes. Another six children were registered to have had one or two episodes of acute pyelonephritis. Overall, antibiotics were prescribed for 66% of the children having had < or = 3 cystitis episodes, two thirds of whom received the antibiotics of first choice. About 30% of all episodes were followed up in general practice. Thirty-eight children were referred (14%), mostly to a paediatrician (76%). Less than one-third of the children who should have been referred was actually referred. CONCLUSION: Treatment of childhood UTIs in Dutch family practice should be improved with respect to prescription, follow-up, and referral. Quality improvement should address the low incidence of urinary tract infections in children in family practice. PMID- 17355618 TI - Evolution of miniaturization and the phylogenetic position of Paedocypris, comprising the world's smallest vertebrate. AB - BACKGROUND: Paedocypris, a highly developmentally truncated fish from peat swamp forests in Southeast Asia, comprises the world's smallest vertebrate. Although clearly a cyprinid fish, a hypothesis about its phylogenetic position among the subfamilies of this largest teleost family, with over 2400 species, does not exist. Here we present a phylogenetic analyses of 227 cypriniform taxa, including 213 cyprinids, based upon complete mitochondrial DNA cytochrome b nucleotide sequences in order to determine the phylogenetic position of Paedocypris and to study the evolution of miniaturization among cyprinids. RESULTS: Our analyses reveal a strongly supported sister group relationship (clade C) between Paedocypris and Sundadanio, another developmentally truncated miniature cyprinid. Clade C was resolved as sister group of a larger clade characterized by small rasborine taxa (clade D). We found that miniaturised taxa are more numerous in the rasborine clade A, formed by clades C and D, than in any other cyprinid clade. The consensus cytb in cyprinids includes 380 amino acids and an incomplete T-- stop codon. We noted that a few cyprinids mostly rasborine taxa placed within clade A had either a TAA or TAG stop codon, 376, 378, or 381 amino acids, and up to 10 base pairs (bp) of noncoding region before the 5' end of the tRNA-Thr. Our relaxed molecular clock estimates revealed high divergence times for the Sundadanio and Paedocypris clades and provide a first temporal framework for the evolution of miniaturization among cyprinids. CONCLUSION: Paedocypris belongs to a clade (Rasborinae clade A) that shows recurrent miniaturization, including both taxa characterized by developmental truncation and by proportioned dwarfism. Its closest relative is another miniaturized taxon, the genus Sundadanio. We conclude that the miniaturized cyprinids with remarkable morphological novelties, like Paedocypris and Danionella, are at the same time the most developmentally truncated taxa. The miniaturized cyprinids with no or few developmental truncations like Boraras, Microrasbora, and Horadandia show no such evolutionary novelties. PMID- 17355619 TI - 2-Arylhydrazononitriles as building blocks in heterocyclic synthesis: A novel route to 2-substituted-1,2,3-triazoles and 1,2,3-triazolo[4,5-b]pyridines. AB - 2-Arylhydrazono-3-oxobutanenitriles 2 was reacted with hydroxylamine hydrochloride to yield amidooxime 3. This was cyclized into the corresponding oxadiazole 4 on refluxing in acetic anhydride. When refluxed in DMF in presence of piperidine, the corresponding 1,2,3-triazoleamine 5 was formed. The latter was acylated to 6 by addition of acetic anhydride while treatment of 5 with malononitrile gave the 1,2,3-triazolo [4,5-b]pyridine 8. Treatment of acetyl derivative 6 with DMFDMA gave enaminone 9. The enaminone 9 was coupled with benzenediazonium chloride to yield phenylazo-1,2,3-triazolo [4,5-b]pyridine 10. Trials to convert compound 14 into 1,2,3-triazolo [4,5-d]pyrimidine 15 via refluxing in AcOH/NH4OAc failed. Instead the hydrolyzed product 5 was formed. PMID- 17355620 TI - Replicative homeostasis III: implications for antiviral therapy and mechanisms of response and non-response. AB - While improved drug regimens have greatly enhanced outcomes for patients with chronic viral infection, antiviral therapy is still not ideal due to drug toxicities, treatment costs, primary drug failure and emergent resistance. New antiviral agents, alternative treatment strategies and a better understanding of viral pathobiology, host responses and drug action are desperately needed. Interferon (IFN) and ribavirin, are effective drugs used to treat hepatitis C (HCV), but the mechanism(s) of their action are uncertain. Error catastrophe (EC), or precipitous loss of replicative fitness caused by genomic mutation, is postulated to mediate ribavirin action, but is a deeply flawed hypothesis lacking empirical confirmation. Paradoxically ribavirin, a proven RNA mutagen, has no impact on HCV viraemia long term, suggesting real viruses, replicating in-vitro, as opposed to mathematical models, replicating in-silico, are likely to resist EC by highly selective replication of fit (~consensus sequence) genomes mediated, in part, by replicative homeostasis (RH), an epicyclic mechanism that dynamically links RNApol fidelity and processivity and other viral protein functions. Replicative homeostasis provides a rational explanation for the various responses seen during treatment of HCV, including genotype-specific and viral load dependent differential response rates, as well as otherwise unexplained phenomena like the transient inhibition and rebound of HCV viraemia seen during ribavirin monotherapy. Replicative homeostasis also suggests a primarily non-immunological mechanism that mediates increased immune responsiveness during treatment with ribavirin (and other nucleos(t)ide analogues), explicating the enhanced second phase clearance of HCV ribavirin promotes and, thus, the apparent immunomodulatory action of ribavirin. More importantly, RH suggests specific new antiviral therapeutic strategies. PMID- 17355621 TI - Experimental based experiences with the introduction of a water safety plan for a multi-located university clinic and its efficacy according to WHO recommendations. AB - BACKGROUND: Due to the high number of immunosuppressed and other predisposed patients hospitals have to control and ensure the microbiological water quality. The origin for the occurrence of pathogenic microorganisms in water pipes is the formation of biofilm. METHODS: For the permanent control of water safety a water safety plan (WSP) was realized as recommended by the WHO following the principle "search and destroy". The WSP is based on an established HACCP concept due to the special focus. The most important measures include the concept for sample taking depending on patient risk. 3 different categories) are distinguished: risk area1 (high infection risk), risk 2 (moderate infection risk), and risk area 3 (not increased infection risk). Additionally to the threshold value of the German law for the quality of drinking water (TrinkwV) three more limiting values were defined (warning, alert, and worst case) for immediate risk adapted reaction. Additional attention has to be focussed on lavatory sinks, which are an open bacterial reservoir. Therefore continuous disinfecting siphons were installed as part of the WSP in high risk areas. If extended technical equipment is not available, especially for immunocompromised patients the following measures are easy to realize: boiled (or sun exposed) water for nursing procedures as well alimentary use, no showering. RESULTS: Comparing data over 3 years the microbial water quality was significantly improved resulting in no new case of nosocomial Legionella pneumoniae and decrease in neonatal sepsis. CONCLUSION: According to average situations with highly contaminated water system the management must be defined with implementation of water task force, immediate providing of special equipment, information of patients and staff and control of the water quality, an example for successful decontamination of the hospital within 24 hours is given. PMID- 17355623 TI - Fast computation of distance estimators. AB - BACKGROUND: Some distance methods are among the most commonly used methods for reconstructing phylogenetic trees from sequence data. The input to a distance method is a distance matrix, containing estimated pairwise distances between all pairs of taxa. Distance methods themselves are often fast, e.g., the famous and popular Neighbor Joining (NJ) algorithm reconstructs a phylogeny of n taxa in time O(n3). Unfortunately, the fastest practical algorithms known for Computing the distance matrix, from n sequences of length l, takes time proportional to l.n2. Since the sequence length typically is much larger than the number of taxa, the distance estimation is the bottleneck in phylogeny reconstruction. This bottleneck is especially apparent in reconstruction of large phylogenies or in applications where many trees have to be reconstructed, e.g., bootstrapping and genome wide applications. RESULTS: We give an advanced algorithm for Computing the number of mutational events between DNA sequences which is significantly faster than both Phylip and Paup. Moreover, we give a new method for estimating pairwise distances between sequences which contain ambiguity Symbols. This new method is shown to be more accurate as well as faster than earlier methods. CONCLUSION: Our novel algorithm for Computing distance estimators provides a valuable tool in phylogeny reconstruction. Since the running time of our distance estimation algorithm is comparable to that of most distance methods, the previous bottleneck is removed. All distance methods, such as NJ, require a distance matrix as input and, hence, our novel algorithm significantly improves the overall running time of all distance methods. In particular, we show for real world biological applications how the running time of phylogeny reconstruction using NJ is improved from a matter of hours to a matter of seconds. PMID- 17355622 TI - The ubiquitination code: a signalling problem. AB - Ubiquitin is a highly versatile post-translational modification that controls virtually all types of cellular events. Over the past ten years we have learned that diverse forms of ubiquitin modifications and of ubiquitin binding modules co exist in the cell, giving rise to complex networks of protein:protein interactions. A central problem that continues to puzzle ubiquitinologists is how cells translate this myriad of stimuli into highly specific responses. This is a classical signalling problem. Here, we draw parallels with the phosphorylation signalling pathway and we discuss the expanding repertoire of ubiquitin signals, signal tranducers and signalling-regulated E3 enzymes. We examine recent advances in the field, including a new mechanism of regulation of E3 ligases that relies on ubiquitination. PMID- 17355624 TI - Duplicated Hox genes in the spider Cupiennius salei. AB - BACKGROUND: Hox genes are expressed in specific domains along the anterior posterior body axis and define the regional identity. In most animals these genes are organized in a single cluster in the genome and the order of the genes in the cluster is correlated with the anterior to posterior expression of the genes in the embryo. The conserved order of the various Hox gene orthologs in the cluster among most bilaterians implies that such a Hox cluster was present in their last common ancestor. Vertebrates are the only metazoans so far that have been shown to contain duplicated Hox clusters, while all other bilaterians seem to possess only a single cluster. RESULTS: We here show that at least three Hox genes of the spider Cupiennius salei are present as two copies in this spider. In addition to the previously described duplicated Ultrabithorax gene, we here present sequence and expression data of a second Deformed gene, and of two Sex comb reduced genes. In addition, we describe the sequence and expression of the Cupiennius proboscipedia gene. The spider Cupiennius salei is the first chelicerate for which orthologs of all ten classes of arthropod Hox genes have been described. The posterior expression boundary of all anterior Hox genes is at the tagma border of the prosoma and opisthosoma, while the posterior boundary of the posterior Hox genes is at the posterior end of the embryo. CONCLUSION: The presence of at least three duplicated Hox genes points to a major duplication event in the lineage to this spider, perhaps even of the complete Hox cluster as has taken place in the lineage to the vertebrates. The combined data of all Cupiennius Hox genes reveal the existence of two distinct posterior expression boundaries that correspond to morphological tagmata boundaries. PMID- 17355625 TI - Modelling the public health impact of male circumcision for HIV prevention in high prevalence areas in Africa. AB - BACKGROUND: Recent clinical trials in Africa, in combination with several observational epidemiological studies, have provided evidence that male circumcision can reduce HIV female-to-male transmission risk by 60% or more. However, the public health impact of large-scale male circumcision programs for HIV prevention is unclear. METHODS: Two mathematical models were examined to explore this issue: a random mixing model and a compartmental model that distinguishes risk groups associated with sex work. In the compartmental model, two scenarios were developed, one calculating HIV transmission and prevalence in a context similar to the country of Botswana, and one similar to Nyanza Province, in western Kenya. RESULTS: In both models, male circumcision programs resulted in large and sustained declines in HIV prevalence over time among both men and women. Men benefited somewhat more than women, but prevalence among women was also reduced substantially. With 80% male circumcision uptake, the reductions in prevalence ranged from 45% to 67% in the two "countries", and with 50% uptake, from 25% to 41%. It would take over a decade for the intervention to reach its full effect. CONCLUSION: Large-scale uptake of male circumcision services in African countries with high HIV prevalence, and where male circumcision is not now routinely practised, could lead to substantial reductions in HIV transmission and prevalence over time among both men and women. PMID- 17355626 TI - Factors influencing change of preoperative treatment intent in a gastrointestinal cancer practice. AB - BACKGROUND: Postoperative assessment of indications for cancer directed surgical procedures frequently differs from preoperative plans. METHODS: Specifically defined preoperative indications and postoperative results were followed prospectively over 48 months in a single surgeon academic practice, and relationships to postoperative outcomes evaluated. RESULTS: Operations were performed on 406 patients with a median age of 61 (range: 18-90). Major operations (n = 303, 75%) involved 270 abdominal resections including pancreatectomies (37%), liver resections (23%), gastrectomies (19%), and others (21%). Preoperative curative (70%), diagnostic (38%), palliative (12%), access (9%), and non-cancer related therapy (21%) goals were in part combined in 176 patients (43%). Postoperative assessment differed from preoperative goals in 118 patients (29%). Predominant reasons were proof of benign disease (n = 35), incomplete resection (R1 or R2, n = 23), unresectability by laparoscopy (n = 21) or laparotomy (n = 21), or others (n = 18). Potential preoperative cure or palliation goals were not achieved in 37% or 15% of cases, respectively. Circumstances of changed treatment intent were specific for disease site. CONCLUSION: Preoperative therapeutic intent frequently differs from postoperative assessments in gastrointestinal cancer, based on shortcomings in diagnosis or therapy. Formulations of precise operative indications are recommended to optimize individual outcomes and avoid unnecessary or ineffective procedures. PMID- 17355627 TI - Signal transduction-related responses to phytohormones and environmental challenges in sugarcane. AB - BACKGROUND: Sugarcane is an increasingly economically and environmentally important C4 grass, used for the production of sugar and bioethanol, a low-carbon emission fuel. Sugarcane originated from crosses of Saccharum species and is noted for its unique capacity to accumulate high amounts of sucrose in its stems. Environmental stresses limit enormously sugarcane productivity worldwide. To investigate transcriptome changes in response to environmental inputs that alter yield we used cDNA microarrays to profile expression of 1,545 genes in plants submitted to drought, phosphate starvation, herbivory and N2-fixing endophytic bacteria. We also investigated the response to phytohormones (abscisic acid and methyl jasmonate). The arrayed elements correspond mostly to genes involved in signal transduction, hormone biosynthesis, transcription factors, novel genes and genes corresponding to unknown proteins. RESULTS: Adopting an outliers searching method 179 genes with strikingly different expression levels were identified as differentially expressed in at least one of the treatments analysed. Self Organizing Maps were used to cluster the expression profiles of 695 genes that showed a highly correlated expression pattern among replicates. The expression data for 22 genes was evaluated for 36 experimental data points by quantitative RT-PCR indicating a validation rate of 80.5% using three biological experimental replicates. The SUCAST Database was created that provides public access to the data described in this work, linked to tissue expression profiling and the SUCAST gene category and sequence analysis. The SUCAST database also includes a categorization of the sugarcane kinome based on a phylogenetic grouping that included 182 undefined kinases. CONCLUSION: An extensive study on the sugarcane transcriptome was performed. Sugarcane genes responsive to phytohormones and to challenges sugarcane commonly deals with in the field were identified. Additionally, the protein kinases were annotated based on a phylogenetic approach. The experimental design and statistical analysis applied proved robust to unravel genes associated with a diverse array of conditions attributing novel functions to previously unknown or undefined genes. The data consolidated in the SUCAST database resource can guide further studies and be useful for the development of improved sugarcane varieties. PMID- 17355628 TI - Rheumatoid peripheral blood phagocytes are primed for activation but have impaired Fc-mediated generation of reactive oxygen species. AB - Significant levels of circulating immune complexes (ICs) containing rheumatoid factors and immunoglobulin G in peripheral blood are a characteristic feature of rheumatoid arthritis (RA). ICs interact through Fc gamma receptors (Fc gammaR) to activate phagocytes in numerous inflammatory processes. The high concentration of neutrophils in synovial fluid during active phases of the disease, together with their destructive capacity, pose important questions as to their role in the pathogenesis of RA. Functional defects in RA or control peripheral blood neutrophil Fc gammaRs were examined with a specific Fc gammaR-mediated reactive oxygen species (ROS) assay. Heterologous cross-linking of Fc gammaRIIa and Fc gammaRIIIb on neutrophils resulted in a significantly decreased production of ROS by RA cells compared with controls matched for age and sex. However, expression and homologous ligation of receptors did not differ between these groups. These data suggest that neutrophil priming does occur before emigration into the joint and that blood neutrophils from patients with RA have a functional impairment in cooperative Fc gammaR-mediated ROS generation. This may account for the increased susceptibility to bacterial infection that arises in patients with severe disease. PMID- 17355629 TI - Transcriptional profiling of Actinobacillus pleuropneumoniae under iron restricted conditions. AB - BACKGROUND: To better understand effects of iron restriction on Actinobacillus pleuropneumoniae and to identify new potential vaccine targets, we conducted transcript profiling studies using a DNA microarray containing all 2025 ORFs of the genome of A. pleuropneumoniae serotype 5b strain L20. This is the first study involving the use of microarray technology to monitor the transcriptome of A. pleuropneumoniae grown under iron restriction. RESULTS: Upon comparing growth of this pathogen in iron-sufficient versus iron-depleted medium, 210 genes were identified as being differentially expressed. Some genes (92) were identified as being up-regulated; many have confirmed or putative roles in iron acquisition, such as the genes coding for two TonB energy-transducing proteins and the hemoglobin receptor HgbA. Transcript profiling also led to identification of some new iron acquisition systems of A. pleuropneumoniae. Genes coding for a possible Yfe system (yfeABCD), implicated in the acquisition of chelated iron, were detected, as well as genes coding for a putative enterobactin-type siderophore receptor system. ORFs for homologs of the HmbR system of Neisseria meningitidis involved in iron acquisition from hemoglobin were significantly up-regulated. Down-regulated genes included many that encode proteins containing Fe-S clusters or that use heme as a cofactor. Supplementation of the culture medium with exogenous iron re-established the expression level of these genes. CONCLUSION: We have used transcriptional profiling to generate a list of genes showing differential expression during iron restriction. This strategy enabled us to gain a better understanding of the metabolic changes occurring in response to this stress. Many new potential iron acquisition systems were identified, and further studies will have to be conducted to establish their role during iron restriction. PMID- 17355630 TI - Pseudomonas aeruginosa contamination of mouth swabs during production causing a major outbreak. AB - BACKGROUND: In 2002 we investigated an outbreak comprising 231 patients in Norway, caused by Pseudomonas aeruginosa and linked to the use of contaminated mouth swabs called Dent-O-Sept. Here we describe the extent of contamination of the swabs, and identify critical points in the production process that made the contamination possible, in order to prevent future outbreaks. METHODS: Environmental investigation with microbiological examination of production, ingredients and product, molecular typing of bacteria and a system audit of production. RESULTS: Of the 1565 swabs examined from 149 different production batches the outbreak strain of P. aeruginosa was detected in 76 swabs from 12 batches produced in 2001 and 2002. In total more than 250 swabs were contaminated with one or more microbial species. P. aeruginosa was detected from different spots along the production line. The audit revealed serious breeches of production regulations. Health care institutions reported non-proper use of the swabs and weaknesses in their purchasing systems. CONCLUSION: Biofilm formation in the wet part of the production is the most plausible explanation for the continuous contamination of the swabs with P. aeruginosa over a period of at least 30 weeks. When not abiding to production regulations fatal consequences for the users may ensue. For the most vulnerable patient groups only documented quality-controlled, high-level disinfected products and items should be used in the oropharynx. PMID- 17355631 TI - Antiviral therapy in neonatal cholestatic cytomegalovirus hepatitis. AB - BACKGROUND: Neonatal hepatitis refers to a heterogeneous group of disorders, caused by many factors including cytomegalovirus infection, revealing similar morphologic changes in the liver of an infant less than 3 months of age. Approximately 40% of cholestasis in infants is due to neonatal hepatitis. It may cause latent or acute cholestatic or chronic hepatitis, including cirrhosis in immunocompetant infant. METHODS: Twelve infants diagnosed with neonatal cytomegalovirus hepatitis in the last one year were included in the study. Group 1 consisted of seven babies treated with ganciclovir for 21 days. Group 2 included five cases who did not receive antiviral treatment. Physical examination, biochemical, serologic and virologic tests were done for both groups at the time of diagnosis and in the third month. RESULTS: Initial levels of total bilirubin, aminotransferases, gamma glutamyl transpeptidase, and alkaline phosphatase revealed a significant decrease after the treatment in Group 1 (p < 0.05) when compared with Group 2. This study revealed that ganciclovir treatment is a safe and effective in cases with cholestatic hepatitis. Similarly, all the patients in the treatment group had evidence of improvement serologically and virologically, while the comparison group did not reveal any significant change(p < 0.01). CONCLUSION: The clinical spectrum of perinatal infection varies from an asymptomatic infection or a mild disease to a severe systemic involvement, including central nervous system. The treatment in the early period of infection improved serologic markers and cholestatic parameters significantly. Further studies will lead us to clarify the efficacy of ganciclovir treatment in the early period of cytomegalovirus hepatitis, and the preventive role of anti-viral therapy on progressive liver disease due to cholestasis and hepatitis in neonatal cytomegalovirus infection. PMID- 17355632 TI - Granular cell tumors of the urinary bladder. AB - BACKGROUND: Granular cell tumors (GCTs) are extremely rare lesions of the urinary bladder with only nine cases being reported in world literature of which one was malignant. Generally believed to be of neural origin based on histochemical, immunohistochemical, and ultrastructural studies; they mostly follow a clinically benign course but are commonly mistaken for malignant tumors since they are solid looking, ulcerated tumors with ill-defined margins. MATERIALS AND METHODS: We herein report two cases of GCTs, one benign and one malignant, presenting with gross hematuria in a 14- and a 47-year-old female, respectively. RESULTS: Histopathology revealed characteristic GCTs with positive immunostaining for neural marker (S-100) and negative immunostaining for epithelial (cytokeratin, Cam 5.2, AE/A13), neuroendocrine (neuron specific enolase, chromogranin A, and synaptophysin) and sarcoma (desmin, vimentin) markers. The benign tumor was successfully managed conservatively with transurethral resection alone while for the malignant tumor, radical cystectomy, hysterectomy with bilateral salpingo oophorectomy, anterior vaginectomy, plus lymph node dissection was done. Both cases show long-term disease free survival. CONCLUSION: We recommend careful pathologic assessment for establishing the appropriate diagnosis and either a conservative or aggressive surgical treatment for benign or localized malignant GCT of the urinary bladder, respectively. PMID- 17355633 TI - Is there a uniform approach to the management of diffuse parenchymal lung disease (DPLD) in the UK? A national benchmarking exercise. AB - BACKGROUND: Benchmarking is the comparison of a process to the work or results of others. We conducted a national benchmarking exercise to determine how UK pulmonologists manage common clinical scenarios in diffuse parenchymal lung disease (DPLD), and to determine current use and availability of investigative resources. We compared management decisions to existing international guidelines. METHODS: Consultant members of the British Thoracic Society were mailed a questionnaire seeking their views on the management of three common scenarios in DPLD. They were asked to choose from various management options for each case. Information was also obtained from the respondents on time served as a consultant, type of institution in which they worked and the availability of a local radiologist and histopathologist with an interest/expertise in thoracic medicine. RESULTS: 370 out of 689 consultants replied (54% response rate). There were many differences in the approach to the management of all three cases. Given a scenario of relapsing pulmonary sarcoidosis in a lady with multiple co morbidities, half of respondents would institute treatment with a variety of immunosuppressants while a half would simply observe. 42% would refer a 57-year old lady with new onset DPLD for a surgical lung biopsy, while a similar number would not. 80% would have referred her for transplantation, but a fifth would not. 50% of consultants from district general hospitals would have opted for a surgical biopsy compared to 24% from cardiothoracic centres: this may reflect greater availability of a radiologist with special interest in thoracic imaging in cardiothoracic centres, obviating the need for tissue diagnosis. Faced with an elderly male with high resolution CT thorax (HRCT) evidence of usual interstitial pneumonia (UIP), three quarters would observe, while a quarter would start immunosuppressants. 11% would refer for a surgical biopsy. 14% of UK pulmonologists responding to the survey revealed they had no access to a radiologist with an interest in thoracic radiology. CONCLUSION: From our survey, it appears there is a lack of consensus in the management of DPLD. This may reflect lack of evidence, lack of resources or a failure to implement current guidelines. PMID- 17355634 TI - Importance of data structure in comparing two dimension reduction methods for classification of microarray gene expression data. AB - BACKGROUND: With the advance of microarray technology, several methods for gene classification and prognosis have been already designed. However, under various denominations, some of these methods have similar approaches. This study evaluates the influence of gene expression variance structure on the performance of methods that describe the relationship between gene expression levels and a given phenotype through projection of data onto discriminant axes. RESULTS: We compared Between-Group Analysis and Discriminant Analysis (with prior dimension reduction through Partial Least Squares or Principal Components Analysis). A geometric approach showed that these two methods are strongly related, but differ in the way they handle data structure. Yet, data structure helps understanding the predictive efficiency of these methods. Three main structure situations may be identified. When the clusters of points are clearly split, both methods perform equally well. When the clusters superpose, both methods fail to give interesting predictions. In intermediate situations, the configuration of the clusters of points has to be handled by the projection to improve prediction. For this, we recommend Discriminant Analysis. Besides, an innovative way of simulation generated the three main structures by modelling different partitions of the whole variance into within-group and between-group variances. These simulated datasets were used in complement to some well-known public datasets to investigate the methods behaviour in a large diversity of structure situations. To examine the structure of a dataset before analysis and preselect an a priori appropriate method for its analysis, we proposed a two-graph preliminary visualization tool: plotting patients on the Between-Group Analysis discriminant axis (x-axis) and on the first and the second within-group Principal Components Analysis component (y-axis), respectively. CONCLUSION: Discriminant Analysis outperformed Between-Group Analysis because it allows for the dataset structure. An a priori knowledge of that structure may guide the choice of the analysis method. Simulated datasets with known properties are valuable to assess and compare the performance of analysis methods, then implementation on real datasets checks and validates the results. Thus, we warn against the use of unchallenging datasets for method comparison, such as the Golub dataset, because their structure is such that any method would be efficient. PMID- 17355635 TI - Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model. AB - BACKGROUND: microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nucleotides in length that have been found to control cell growth, differentiation and apoptosis. They negatively regulate target genes and have recently been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. Recently, a point mutation in the BRAF gene leading to a V600E substitution has been identified as the most common genetic change in papillary thyroid carcinoma (PTC) occurring in 29-69% of cases. This mutation leads to aberrant MAPK activation that is implicated in tumourigenesis. AIM: The aim of this study was to identify the effect that BRAF oncogene has on post-transcriptional regulation in PTC by using microRNA analysis. RESULTS: A unique miRNA expression signature differentiated between PTC cell lines with BRAF mutations and a normal thyroid cell line. 15 miRNAs were found to be upregulated and 23 miRNAs were downregulated. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis. miRNA profiling will assist in the elucidation of disease pathogenesis and identification biomarkers and targets. PMID- 17355636 TI - A prospective study of decline in fat free mass and skeletal muscle strength in chronic obstructive pulmonary disease. AB - BACKGROUND: Skeletal muscle depletion is an important complication of chronic obstructive pulmonary disease (COPD) but little prospective data exists about the rate at which it occurs and the factors that promote its development. We therefore prospectively investigated the impact of disease severity, exacerbation frequency and treatment with corticosteroids on change in body composition and maximum isometric quadriceps strength (QMVC) over one year. METHODS: 64 patients with stable COPD (FEV1 mean (SD) 35.8(18.4) %predicted) were recruited from clinic and studied on two occasions one year apart. Fat free mass was determined using bioelectrical impedance analysis and a disease specific regression equation. RESULTS: QMVC fell from 34.8(1.5) kg to 33.3(1.5) kg (p = 0.04). The decline in quadriceps strength was greatest in those with the highest strength at baseline (R -0.28 p = 0.02) and was not correlated with lung function, exacerbation frequency or steroid treatment. Decline in fat free mass was similarly higher in those with largest FFM at baseline (R = -0.31 p = 0.01) but was more strongly correlated with greater gas trapping (R = -0.4 p = 0.001). Patients with frequent exacerbations (>1 per year) (n = 36) experienced a greater decline in fat free mass compared to infrequent exacerbators (n = 28) -1.3(3.7)kg vs. +1.2(3.1)kg (p = 0.005), as did patients on maintenance oral steroids (n = 8) -2.8(3.3) kg vs. +0.2(3.5) kg (p = 0.024) whereas in those who stopped smoking (n = 7) fat free mass increased; +2.7(3.1) kg vs. -0.51(3.5) kg (p = 0.026). CONCLUSION: Decline in fat free mass in COPD is associated with worse lung function, continued cigarette consumption and frequent exacerbations. Factors predicting progression of quadriceps weakness could not be identified from the present cohort. PMID- 17355637 TI - A comparative genomics approach to identifying the plasticity transcriptome. AB - BACKGROUND: Neuronal activity regulates gene expression to control learning and memory, homeostasis of neuronal function, and pathological disease states such as epilepsy. A great deal of experimental evidence supports the involvement of two particular transcription factors in shaping the genomic response to neuronal activity and mediating plasticity: CREB and zif268 (egr-1, krox24, NGFI-A). The gene targets of these two transcription factors are of considerable interest, since they may help develop hypotheses about how neural activity is coupled to changes in neural function. RESULTS: We have developed a computational approach for identifying binding sites for these transcription factors within the promoter regions of annotated genes in the mouse, rat, and human genomes. By combining a robust search algorithm to identify discrete binding sites, a comparison of targets across species, and an analysis of binding site locations within promoter regions, we have defined a group of candidate genes that are strong CREB- or zif268 targets and are thus regulated by neural activity. Our analysis revealed that CREB and zif268 share a disproportionate number of targets in common and that these common targets are dominated by transcription factors. CONCLUSION: These observations may enable a more detailed understanding of the regulatory networks that are induced by neural activity and contribute to the plasticity transcriptome. The target genes identified in this study will be a valuable resource for investigators who hope to define the functions of specific genes that underlie activity-dependent changes in neuronal properties. PMID- 17355638 TI - Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice. AB - BACKGROUND: The obesity epidemic has prompted the search for candidate genes capable of influencing adipose function. One such candidate, that encoding phospholipid scramblase 3 (PLSCR3), was recently identified, as genetic deletion of it led to lipid accumulation in abdominal fat pads and changes characteristic of metabolic syndrome. Because adipose tissue is increasingly recognized as an endocrine organ, capable of releasing small molecules that modulate disparate physiological processes, we examined the plasma from wild-type, Plscr1-/-, Plscr3 /- and Plscr1&3-/- mice. Using an untargeted comprehensive metabolite profiling approach coupled with targeted gene expression analyses, the perturbed biochemistry and functional redundancy of PLSCR proteins was assessed. RESULTS: Nineteen metabolites were differentially and similarly regulated in both Plscr3-/ and Plscr1&3-/- animals, of which five were characterized from accurate mass, tandem mass spectrometry data and their correlation to the Metlin database as lysophosphatidylcholine (LPC) species enriched with C16:1, C18:1, C20:3, C20:5 and C22:5 fatty acids. No significant changes in the plasma metabolome were detected upon elimination of PLSCR1, indicating that increases in pro inflammatory lipids are specifically associated with the obese state of Plscr3 deficient animals. Correspondingly, increases in white adipose lipogenic gene expression confirm a role for PLSCR3 in adipose lipid metabolism. CONCLUSION: The untargeted profiling of circulating metabolites suggests no detectable functional redundancies between PLSCR proteins; however, this approach simultaneously identified previously unrecognized lipid metabolites that suggest a novel molecular link between obesity, inflammation and the downstream consequences associated with PLSCR3-deficiency. PMID- 17355639 TI - The influenza pandemic preparedness planning tool InfluSim. AB - BACKGROUND: Planning public health responses against pandemic influenza relies on predictive models by which the impact of different intervention strategies can be evaluated. Research has to date rather focused on producing predictions for certain localities or under specific conditions, than on designing a publicly available planning tool which can be applied by public health administrations. Here, we provide such a tool which is reproducible by an explicitly formulated structure and designed to operate with an optimal combination of the competing requirements of precision, realism and generality. RESULTS: InfluSim is a deterministic compartment model based on a system of over 1,000 differential equations which extend the classic SEIR model by clinical and demographic parameters relevant for pandemic preparedness planning. It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalizations, deaths and work days lost due to sickness, all of which may be associated with economic aspects. The software is programmed in Java, operates platform independent and can be executed on regular desktop computers. CONCLUSION: InfluSim is an online available software http://www.influsim.info which efficiently assists public health planners in designing optimal interventions against pandemic influenza. It can reproduce the infection dynamics of pandemic influenza like complex computer simulations while offering at the same time reproducibility, higher computational performance and better operability. PMID- 17355640 TI - Tumor-specific T cells signal tumor destruction via the lymphotoxin beta receptor. AB - BACKGROUND: Previously, we reported that adoptively transferred perforin k/o (PKO), and IFN-gamma k/o (GKO), or perforin/IFN-gamma double k/o (PKO/GKO) effector T cells mediated regression of B16BL6-D5 (D5) pulmonary metastases and showed that TNF receptor signaling played a critical role in mediating tumor regression. In this report we investigated the role of lymphotoxin-alpha (LT alpha) as a potential effector molecules of tumor-specific effector T cells. METHODS: Effector T cells were generated from tumor vaccine-draining lymph node (TVDLN) of wt, GKO, LT-alpha deficient (LKO), or PKO/GKO mice and tested for their ability to mediate regression of D5 pulmonary metastases in the presence or absence of LT-betaR-Fc fusion protein or anti-IFN-gamma antibody. Chemokine production by D5 tumor cells was determined by ELISA, RT-PCR and Chemotaxis assays. RESULTS: Stimulated effector T cells from wt, GKO, or PKO/GKO mice expressed ligands for LT-beta receptor (LT-betaR). D5 tumor cells were found to constitutively express the LT-betaR. Administration of LT-betaR-Fc fusion protein completely abrogated the therapeutic efficacy of GKO or PKO/GKO but not wt effector T cells (p < 0.05). Consistent with this observation, therapeutic efficacy of effector T cells deficient in LT-alpha, was greatly reduced when IFN gamma production was neutralized. While recombinant LT-alpha1beta2 did not induce apoptosis of D5 tumor cells in vitro, it induced secretion of chemokines by D5 that promoted migration of macrophages. CONCLUSION: The contribution of LT-alpha expression by effector T cells to anti-tumor activity in vivo was not discernable when wt effector T cells were studied. However, the contribution of LT-beta R signaling was identified for GKO or PKO/GKO effector T cells. Since LT-alpha does not directly induce killing of D5 tumor cells in vitro, but does stimulate D5 tumor cells to secrete chemokines, these data suggest a model where LT-alpha expression by tumor-specific effector T cells interacts via cross-linking of the LT-betaR on tumor cells to induce secretion of chemokines that are chemotactic for macrophages. While the contribution of macrophages to tumor elimination in our system requires additional study, this model provides a possible explanation for the infiltration of inate effector cells that is seen coincident with tumor regression. PMID- 17355642 TI - A new technique for mandibular osteotomy. AB - Sagittal split osteotomy (SSO) is a surgical technique largely employed for mandibular mobilizations in orthognatic procedures. However, the traditional design of buccal osteotomy, located at the junction of mandibular ramus and body, may prevent more extensive sliding between the bone segments, particularly on the advance, laterality and verticality of the mandibular body. The author proposes a new technical and conceptual solution, in which osteotomy is performed in a more distal region, next to the mental foramen. Technically, the area of contact between medullary-cancellous bone surfaces is increased, resulting in larger sliding rates among bone segments; it also facilitates the use of rigid fixation systems, with miniplates and monocortical screws. Conceptually, it interferes with the resistance arm of the mandible, seen as an interpotent lever of the third gender. PMID- 17355641 TI - Evolution and the complexity of bacteriophages. AB - BACKGROUND: The genomes of both long-genome (> 200 Kb) bacteriophages and long genome eukaryotic viruses have cellular gene homologs whose selective advantage is not explained. These homologs add genomic and possibly biochemical complexity. Understanding their significance requires a definition of complexity that is more biochemically oriented than past empirically based definitions. HYPOTHESIS: Initially, I propose two biochemistry-oriented definitions of complexity: either decreased randomness or increased encoded information that does not serve immediate needs. Then, I make the assumption that these two definitions are equivalent. This assumption and recent data lead to the following four-part hypothesis that explains the presence of cellular gene homologs in long bacteriophage genomes and also provides a pathway for complexity increases in prokaryotic cells: (1) Prokaryotes underwent evolutionary increases in biochemical complexity after the eukaryote/prokaryote splits. (2) Some of the complexity increases occurred via multi-step, weak selection that was both protected from strong selection and accelerated by embedding evolving cellular genes in the genomes of bacteriophages and, presumably, also archaeal viruses (first tier selection). (3) The mechanisms for retaining cellular genes in viral genomes evolved under additional, longer-term selection that was stronger (second tier selection). (4) The second tier selection was based on increased access by prokaryotic cells to improved biochemical systems. This access was achieved when DNA transfer moved to prokaryotic cells both the more evolved genes and their more competitive and complex biochemical systems. TESTING THE HYPOTHESIS: I propose testing this hypothesis by controlled evolution in microbial communities to (1) determine the effects of deleting individual cellular gene homologs on the growth and evolution of long genome bacteriophages and hosts, (2) find the environmental conditions that select for the presence of cellular gene homologs, (3) determine which, if any, bacteriophage genes were selected for maintaining the homologs and (4) determine the dynamics of homolog evolution. IMPLICATIONS OF THE HYPOTHESIS: This hypothesis is an explanation of evolutionary leaps in general. If accurate, it will assist both understanding and influencing the evolution of microbes and their communities. Analysis of evolutionary complexity increase for at least prokaryotes should include analysis of genomes of long genome bacteriophages. PMID- 17355643 TI - Frequencies of single nucleotide polymorphisms in genes regulating inflammatory responses in a community-based population. AB - BACKGROUND: Allele frequencies reported from public databases or articles are mostly based on small sample sizes. Differences in genotype frequencies by age, race and sex have implications for studies designed to examine genetic susceptibility to disease. In a community-based cohort of 9,960 individuals, we compared the allele frequencies of 49 single nucleotide polymorphisms (SNPs) of genes involved in inflammatory pathways to the frequencies reported on public databases, and examined the genotypes frequencies by age and sex. The genes in which SNPs were analyzed include CCR2, CCR5, COX1, COX2, CRP, CSF1, CSF2, IFNG, IL1A, IL1B, IL2, IL4, IL6, IL8, IL10, IL13, IL18, LTA, MPO, NOS2A, NOS3, PPARD, PPARG, PPARGC1 and TNF. RESULTS: Mean(SD) age was 53.2(15.5); 98% were Caucasians and 62% were women. Only 1 out of 33 SNPs differed from the SNP500Cancer database in allele frequency by >10% in Caucasians (n = 9,831), whereas 12 SNPs differed by >10% (up to 50%) in African Americans (n = 105). Two out of 15 SNPs differed from the dbSNP database in allele frequencies by >10% in Caucasians, and 5 out of 15 SNPs differed by >10% in African Americans. Age was similar across most genotype groups. Genotype frequencies did not differ by sex except for TNF(rs1799724), IL2(rs2069762), IL10(rs1800890), PPARG(rs1801282), and CRP(rs1800947) with differences of less than 4%. CONCLUSION: When estimating the size of samples needed for a study, particularly if a reference sample is used, one should take into consideration the size and ethnicity of the reference sample. Larger sample size is needed for public databases that report allele frequencies in non-Caucasian populations. PMID- 17355644 TI - Feasibility and results of a randomised pilot-study of pre-discharge occupational therapy home visits. AB - BACKGROUND: Pre-discharge home visits aim to maximise independence in the community. These visits involve assessment of a person in their own home prior to discharge from hospital, typically by an occupational therapist. The therapist may provide equipment, adapt the home environment and/or provide education. The aims of this study were to investigate the feasibility of a randomised controlled trial in a clinical setting and the effect of pre-discharge home visits on functional performance in older people undergoing rehabilitation. METHODS: Ten patients participating in an inpatient rehabilitation program were randomly assigned to receive either a pre-discharge home visit (intervention), or standard practice in-hospital assessment and education (control), both conducted by an occupational therapist. The pre-discharge home visit involved assessment of the older person's function and environment, and education, and took an average of 1.5 hours. The hospital-based interview took an average of 40 minutes. Outcome data were collected by a blinded assessor at 0, 2, 4, 8 and 12 weeks. Outcomes included performance of activities of daily living, reintegration to community living, quality of life, readmission and fall rates. RESULTS: Recruitment of 10 participants was slow and took three months. Observed performance of functional abilities did not differ between groups due to the small sample size. Difference in activities of daily living participation, as recorded by the Nottingham Extended Activities of Daily Living scale, was statistically significant but wide confidence intervals and low statistical power limit interpretation of results. CONCLUSION: Evaluation of pre-discharge home visits by occupational therapists in a rehabilitation setting is feasible, but a more effective recruitment strategy for a main study is favored by application of a multi-centre setting. PMID- 17355646 TI - Etomidate and rapid sequence intubation. PMID- 17355645 TI - Ethnobotanical study of medicinal plants used by people in Zegie Peninsula, Northwestern Ethiopia. AB - An ethnobotanical study was conducted from October 2005 to June 2006 to investigate the uses of medicinal plants by people in Zegie Peninsula, northwestern Ethiopia. Information was gathered from 200 people: 70 female and 130 males, using semistructured questionnaire. Of which, six were male local healers. The informants, except the healers, were selected randomly and no appointment was made prior to the visits. Informant consensus factor (ICF) for category of ailments and the fidelity level (FL) of the medicinal plants were determined. Sixty-seven medicinal plants used as a cure for 52 ailments were documented. They are distributed across 42 families and 64 genera. The most frequently utilized plant part was the underground part (root/rhizome/bulb) (42%). The largest number of remedies was used to treat gastrointestinal disorder and parasites infections (22.8%) followed by external injuries and parasites infections (22.1%). The administration routes are oral (51.4%), external (38.6%), nasal (7.9%), and ear (2.1%). The medicinal plants that were presumed to be effective in treating a certain category of disease, such as 'mich' and febrile diseases (0.80) had higher ICF values. This probably indicates a high incidence of these types of diseases in the region, possibly due to the poor socio-economic and sanitary conditions of this people. The medicinal plants that are widely used by the local people or used as a remedy for a specific ailment have higher FL values (Carissa spinarum, Clausena anisata, Acokanthera schimperi, Calpurnia aurea, Ficus thonningii, and Cyphostemma junceum) than those that are less popular or used to treat more than one type of ailments (Plumbago zeylanicum, Dorstenia barnimiana). PMID- 17355647 TI - Emergency department discharge instructions comprehension and compliance study. AB - OBJECTIVES: To assess patient comprehension of emergency department discharge instructions and to describe other predictors of patient compliance with discharge instructions. METHODS: Patients departing from the emergency department of an inner-city teaching hospital were invited to undergo a structured interview and reading test, and to participate in a follow-up telephone interview 2 weeks later. Two physicians, blinded to the other's data, scored patient comprehension of discharge information and compliance with discharge instructions. Inter-rater reliability was assessed using a kappa-weighted statistic, and correlations were assessed using Spearman's rank correlation coefficient and Fisher's exact test. RESULTS: Of 106 patients approached, 88 (83%) were enrolled. The inter-rater reliability of physician rating scores was high (kappa = 0.66). Approximately 60% of subjects demonstrated reading ability at or below a Grade 7 level. Comprehension was positively associated with reading ability (r = 0.29, p = 0.01) and English as first language (r = 0.27, p = 0.01). Reading ability was positively associated with years of education (r = 0.43, p < 0.0001) and first language (r = 0.24, p = 0.03), and inversely associated with age (r = -0.21, p = 0.05). Non-English first language and need for translator were associated with poorer comprehension of discharge instructions but not related to compliance. Compliance with discharge instructions was correlated with comprehension (r = 0.31, p = 0.01) but not associated with age, language, education, years in anglophone country, reading ability, format of discharge instructions, follow-up modality or association with a family physician. CONCLUSIONS: Emergency department patients demonstrated poor reading skills. Comprehension was the only factor significantly related to compliance; therefore, future interventions to improve compliance with emergency department instructions will be most effective if they focus on improving comprehension. PMID- 17355648 TI - Patient expectations of emergency department care: phase I--a focus group study. AB - OBJECTIVES: To assess patient comprehension of emergency department discharge instructions and to describe other predictors of patient compliance with discharge instructions. METHODS: Patients departing from the emergency department of an inner-city teaching hospital were invited to undergo a structured interview and reading test, and to participate in a follow-up telephone interview 2 weeks later. Two physicians, blinded to the other's data, scored patient comprehension of discharge information and compliance with discharge instructions. Inter-rater reliability was assessed using a kappa-weighted statistic, and correlations were assessed using Spearman's rank correlation coefficient and Fisher's exact test. RESULTS: Of 106 patients approached, 88 (83%) were enrolled. The inter-rater reliability of physician rating scores was high (kappa = 0.66). Approximately 60% of subjects demonstrated reading ability at or below a Grade 7 level. Comprehension was positively associated with reading ability (r = 0.29, p = 0.01) and English as first language (r = 0.27, p = 0.01). Reading ability was positively associated with years of education (r = 0.43, p < 0.0001) and first language (r = 0.24, p = 0.03), and inversely associated with age (r = -0.21, p = 0.05). Non-English first language and need for translator were associated with poorer comprehension of discharge instructions but not related to compliance. Compliance with discharge instructions was correlated with comprehension (r = 0.31, p = 0.01) but not associated with age, language, education, years in anglophone country, reading ability, format of discharge instructions, follow-up modality or association with a family physician. CONCLUSIONS: Emergency department patients demonstrated poor reading skills. Comprehension was the only factor significantly related to compliance; therefore, future interventions to improve compliance with emergency department instructions will be most effective if they focus on improving comprehension. PMID- 17355649 TI - Influenza vaccination rate among emergency department personnel: a survey of four teaching hospitals. AB - OBJECTIVES: To determine influenza vaccination rates and attitudes toward vaccination among emergency department health care workers at 4 Ontario teaching hospitals. METHODS: During the influenza season of 1999-2000 a confidential 28 item survey was distributed to emergency physicians and residents, nurses, respiratory therapists, and other allied health care workers at the emergency departments of 4 London, Ontario teaching hospitals. RESULTS: Of 426 surveys distributed, 343 were returned, for an overall response rate of 80.5%. The mean age of respondents was 38.5 years (standard deviation = 8.3), 74.3% were female, and 86.6% were non-smokers. The overall vaccination rate was 37.0% (95% confidence interval, 31.9%-42.4%). Vaccination rates were 45.9% for respiratory therapists, 35.3% for emergency physicians and residents, 34.5% for nurses and 27.1% for other allied health care workers (p = 0.083). Multivariate logistic regression analysis revealed that age >or=41 and a chronic medical condition were positively associated with influenza vaccination (p < 0.05). Close to one-third of respondents (28.3%) believed that adverse affects were common, 51.6% believed vaccination was effective, 52% would support a program to improve vaccination rates among emergency department staff, and 24.4% would support mandatory vaccination for this population. Only 26.8% believed that patients were at increased risk of contracting influenza from emergency department staff, but 58.3% perceived that emergency department staff were at increased risk of contracting influenza through exposure to patients. CONCLUSIONS: In this study, only 37% of emergency department health care workers were immunized against influenza, with chronic illness and older age being the only 2 significant correlates. Strategies to improve emergency department health care worker attitudes toward influenza vaccination for themselves and to increase vaccination rates for this population should be developed. PMID- 17355650 TI - The role of clopidogrel in the emergency department. PMID- 17355651 TI - [Revisions to the Canadian Emergency Department Triage and Acuity Scale implementation guidelines]. PMID- 17355652 TI - Emergency medicine teaching faculty perceptions about formal academic sessions: "What's in it for us?". AB - BACKGROUND: Little is known about factors affecting emergency physician attendance at formal academic teaching sessions or what emergency physicians believe to be the benefits derived from attending these activities. OBJECTIVES: To determine what factors influence emergency medicine faculty attendance at formal academic rounds, what benefits they derive from attendance, and what differences in perceptions there are between full-time clinical and part-time clinical academic faculty. METHODS: A survey was sent to all emergency physicians with academic appointments at one institution. Responses were tabulated dichotomously (yes/no) for checklist answers and analyzed using a 2-person grounded theory approach for open answers based on an a priori analysis plan. Differences between full-time and part-time faculty were compared using the chi squared test for significance. RESULTS: Response rate was 73.8% (48/65). Significant impediments to attendance included clinical responsibilities (75%), professional responsibilities (52.1%), personal responsibilities (33.3%), location (31.2%) and time (27.1%). Perceived benefits of attending rounds were: continuing medical education, social interaction, teaching opportunities, interaction with residents, comparing one's practice with peers, improving teaching techniques, and enjoyment of the format. There were no statistically significant differences between groups' responses. CONCLUSIONS: Emergency physicians in our study attend formal teaching sessions infrequently, suggesting that the perceived benefits do not outweigh impediments to attendance. The single main impediment, competing responsibilities, is difficult to modify for emergency physicians. Strategies to increase faculty attendance should focus on enhancing the main perceived benefits: continuing medical education, social interaction and educational development. Faculty learn from themselves and from residents during formal teaching sessions. PMID- 17355653 TI - Hypothermic modulation of anoxic brain injury in adult survivors of cardiac arrest: a review of the literature and an algorithm for emergency physicians. AB - Anoxic brain injury is a common outcome after cardiac arrest. Despite substantial research into the pathophysiology and management of this injury, a beneficial treatment modality has not been previously identified. Recent studies show that induced hypothermia reduces mortality and improves neurological outcomes in patients resuscitated from ventricular fibrillation. This article reviews the literature on induced hypothermia for anoxic brain injury and summarizes a treatment algorithm proposed by the Canadian Association of Emergency Physicians Critical Care Committee for hypothermia induction in cardiac arrest survivors. PMID- 17355654 TI - Vasopressin versus epinephrine for out-of-hospital cardiopulmonary resuscitation. PMID- 17355655 TI - Acute pneumoperitoneum following coitus. AB - Vaginal rupture leading to pneumoperitoneum is well documented to occur after hysterectomy or surgery. However, it is extremely rare in a young woman following conventional intercourse. We report one such case. A 16-year-old woman presented to the accident and emergency department with a clinical picture of an acute abdomen. Results of radiography showed gas under the diaphragm, suggesting the possibility of bowel perforation. A detailed sexual history pointed toward the possibility of vaginal trauma. Diagnosis was confirmed on examination under anesthesia, and the tear repaired. A concomitant laparoscopy ruled out any other intra-abdominal injury. This case reminds us that acute peritoneum can occur after sexual intercourse and also reiterates the importance of a detailed sexual history and vaginal examination in young women presenting with an acute abdomen. PMID- 17355656 TI - Predicting intervention in renal colic patients after emergency department evaluation. AB - OBJECTIVES: There is no set of prospectively validated criteria to identify the emergency department (ED) patients with renal colic who are most likely to eventually have to undergo an intervention. This study prospectively assessed predictors of intervention in this patient population. METHODS: This prospective cohort study included adult patients with renal colic who presented to 2 tertiary care hospital EDs. Patients had an 18-variable data form completed by an emergency physician and a radiological study to confirm urolithiasis. After discharge, patients were followed at 1 and 4 weeks to assess for intervention. The outcome criteria included the patient having had at least 1 of the following procedures performed: extracorporeal shockwave lithotripsy (ESWL), ureteroscopy, percutaneous nephrostomy or open surgery. Data were analyzed using appropriate univariate techniques, and those variables associated with intervention were combined using logistic regression analysis. RESULTS: Over an 8-month period, 245 patients with confirmed urolithiasis were followed; 20% (95% confidence interval [CI] 15%-25%) eventually had a procedure to remove their calculi. Three variables were significantly correlated with having a procedure: i) size of calculus >or= 6 mm (odds ratio [OR] 10.7, 95% CI 4.6-24.8), ii) location of calculus above mid ureter (OR 6.9, 95% CI 3.0-15.9), and iii) Visual Analogue Scale score for pain at discharge from the ED >or= 2 cm (OR 2.6, 95% CI 1.0-6.8). The area under receiver operating characteristic curve was 0.77 (95% C I 0.70-0.84) (p < 0.001). If all variables were present there was a 90% probability of the patient having an intervention performed within 4 weeks of discharge from the ED. Conversely, if none of the variables were present there was only a 4% probability of an intervention. Overall, the model had a sensitivity of 92% (95% CI 89%-96%) and a specificity of 63% (95% CI 57%-69%). CONCLUSIONS: This study has identified variables that could potentially be used to identify those renal colic patients who require an intervention after ED evaluation. Future studies will prospectively validate this model. PMID- 17355657 TI - Treatment variability and outcome differences in the emergency department management of alcohol withdrawal. AB - OBJECTIVE: Evidence suggests that symptom-triggered benzodiazepine treatment for patients with alcohol withdrawal reduces complication rates and emergency department lengths of stay. Our objective was to describe the management of alcohol withdrawal in 2 urban emergency departments. METHODS: A structured chart audit was performed for patients with alcohol-related problems who presented to 2 Toronto hospitals over a 2-year period. RESULTS: A total of 209 emergency department charts were audited. Patient characteristics were similar in both hospitals. None of the patients had been assessed using the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. Patients at one hospital received substantially higher mean diazepam doses (64 mg v. 26 mg; p < 0.001) than did the patients at the other hospital, and the patients at the first hospital had fewer seizures during their emergency department stay (1% v. 9%; p = 0.012). Patients spent an average of 9 hours and 40 minutes in the emergency department. CONCLUSION: There is significant variability in the documentation and treatment of alcohol withdrawal. Lower benzodiazepine doses are associated with higher rate of withdrawal seizures and prolonged emergency department length of stay. A standardized approach using symptom-triggered management is likely to improve outcomes for patients presenting with alcohol withdrawal. PMID- 17355658 TI - A survey to describe sleep-facilitating substances used by Canadian emergency physicians. AB - BACKGROUND: Because night shifts disrupt the normal circadian rhythm, sleep management is crucial for emergency physicians. The purpose of the survey was to describe the use of sleep-facilitating substances (SFSs) by emergency physicians before or after a night shift and to evaluate factors associated with their use. METHODS: All members of the Canadian Association of Emergency Physicians with a Canadian postal address were mailed a copy of the survey. Canadian physicians were eligible if they worked at least one night shift per month and spent 50% or more of their time in emergency medicine. Logistic regression was used to identify characteristics most predictive of using SFSs before or after a night shift. RESULTS: Of the 1621 surveys mailed, 805 were returned completed, for a response rate of 49.6%. Of these, 628 respondents met inclusion criteria and 215 respondents (34%) reported consuming at least one SFS in their career to help them sleep around a night shift. The use of an SFS before a night shift was associated with the use of SFSs after a night shift (odds ratio [OR] 3.8; 95% confidence interval [CI] 2.4-5.9) and the use of SFSs at other times (OR 3.8; 95% CI 2.1-6.6). The use of SFSs after a night shift was associated with the use of a sleep-facilitating technique before a night shift (OR 2.1; 95% CI 1.3-3.3); use of an SFS before a night shift (OR 4.0; 95% CI 2.4-6.4); use of SFSs at other times (OR 4.7; 95% CI 2.6-8.4); and success of a nap before the night shift (OR 0.46; 95% CI 0.25-0.83). CONCLUSION: The rate of SFS use is similar in emergency physicians and other shift workers. Emergency physicians who use SFSs before or after a night shift are more likely to use them at other times as well, and less likely to use them if they nap successfully prior to a night shift. PMID- 17355659 TI - Ontario's alternate funding arrangements for emergency departments: the impact on the emergency physician workforce. AB - BACKGROUND: Difficulty maintaining physician staffing in emergency departments (EDs) prompted the government of Ontario to offer alternate funding arrangements (AFAs) to replace fee-for-service remuneration for physicians working in EDs. OBJECTIVE: To analyze the effect of AFAs on physician staffing and practice patterns. METHODS: We obtained Ontario Health Insurance Program fee-for-service and shadow-billing records for all physician services provided in EDs one year before and one year after implementation of an ED AFA. Only sites with reliable billing data were retained. Physicians were assigned to small/rural, community or teaching hospital groups based on their billing claims. For each hospital type, and all hospitals combined, we compared the pre- and post-AFA periods in terms of the number of physicians working regularly in the ED and their workload. As a possible unintended consequence of AFAs, we also compared physicians' involvement in primary care. RESULTS: Overall, 76.2% of eligible hospitals adopted an ED AFA, of which 49 (42.6%) were included in our study (16 small/rural, 27 community and 6 teaching hospitals). In the post-AFA period, the number of physicians working in EDs increased by 7, from 674 to 681, representing a 1.0% increase overall in the workforce (p = 0.84). The change varied by hospital type, from a 5.8% increase in teaching hospitals to a 2.2% decrease in community hospitals, though none was significant. In the post-AFA period, the number of physicians working a moderate number of days per month increased from 190 to 214, representing a 3.2% absolute increase (p = 0.39), and the number working few (<5) or many (>10) days per month decreased. Post-AFA, the number of physicians working in EDs who also provided primary care services decreased by 1.7%, from 544 to 535 (p = 0.10). CONCLUSION: Emergency department AFAs have been widely adopted in Ontario, but have not been associated with substantial changes in the overall physician workforce in EDs. However, trends toward increased physician numbers were seen in small/rural and teaching hospitals. There was little evidence of any adverse effects on the provision of primary care services by physicians. PMID- 17355660 TI - Patients who leave the emergency department without being seen by a physician: a control-matched study. AB - OBJECTIVE: To describe the socio-demographic characteristics and clinical outcomes of patients who leave the emergency department (ED) without being seen by a physician. METHODS: This 3-month prospective study was conducted at a downtown Toronto teaching hospital. Patients who left the ED without being seen (LWBS) were matched with controls based on registration time and triage level. Subjects and controls were interviewed by telephone within 1 week after leaving the ED. RESULTS: During the study period, 386 (3.57%) of 10,808 ED patients left without being seen. One-third of these had no fixed address or no telephone, and only 92 (23.8%) consented to a telephone interview. They cited excessive wait time as the most common reason for leaving the ED (in 36.7% of cases). Despite leaving the ED without being seen, they were no more likely than those in the control group to seek follow-up medical attention (70 % in both groups). Among those from both groups who did seek follow-up, the LWBS patients were more likely to do so the same day or the day after leaving the ED. The LWBS patients often lacked a regular physician (39.1% v. 21.7%; p = 0.01) and were more likely to attend an ED or urgent care clinic (34.8% v. 12.0%; p < 0.001). Controls were more likely to follow up with a family physician (37.0% v. 23.9%; p = 0.06). The LWBS and control groups did not differ in subjective health status at 48 hours after leaving the ED, nor in subsequent re-investigation in hospital. CONCLUSIONS: Patients who leave the ED without being seen have different socio demographic features, methods of accessing the health care system, affiliations and expectations than the general ED population. They are often socially disenfranchised, with limited access to traditional primary care. These patients are generally low acuity, but they are at risk of important and avoidable adverse outcomes. PMID- 17355661 TI - Myth: Atropine should be administered before succinylcholine for neonatal and pediatric intubation. AB - Succinylcholine is often used to facilitate neonatal and pediatric rapid sequence intubation in the emergency department, and most relevant literature recommends administering atropine prior to succinylcholine to reduce the risk of bradycardia. Given the potential complications associated with combining these medications, we searched the published literature for evidence supporting this practice. Most studies recommending atropine premedication were undertaken in the operating room setting and pertained to repeated succinylcholine dosing. Furthermore, there is little published evidence to indicate that succinylcholine related bradycardia is a clinically important side effect. Several authors have called for the practice to cease, but, to date, these calls have gone unheeded. We found no evidence supporting atropine's use in pediatric patients prior to single-dose succinylcholine. Atropine premedication for emergency department rapid sequence intubation is unnecessary and should not be viewed as a "standard of care." PMID- 17355662 TI - Coronary artery occlusion following blunt chest trauma: a case report and review of the literature. AB - Blunt chest trauma causing coronary artery occlusion and myocardial infarction is a rare but potentially fatal condition. We present the case of a healthy 29-year old man who developed a myocardial infarction due to complete occlusion of the proximal right coronary artery following blunt chest trauma. A review of the literature found 63 cases of previously healthy patients under 40 years of age who developed coronary artery occlusion following blunt chest trauma; diagnosis in all cases had been proven by angiography or during autopsy. The presentation, results of electrocardiography and echocardiography and laboratory findings of these patients are described. PMID- 17355663 TI - Non-operative management of a high-pressure water injection injury to the hand. AB - High-pressure injection injuries to the hand are work-related injuries that can take a devastating toll on the functionality of the affected extremity. Chemical injections are a surgical emergency. Injuries involving only water injection are rarer and have variable management strategies. We report a case of high-pressure injection hand injury due to water only. The patient was managed non-operatively with parenteral antibiotics, narcotics and elevation, with good outcome. We present a review of the literature on high-pressure injection injury. PMID- 17355664 TI - An unusual cause of shock after cardiac catheterization. PMID- 17355665 TI - Use of automated external defibrillators for children. ILCOR Advisory Statement, October 2002. PMID- 17355666 TI - Therapeutic hypothermia after cardiac arrest. ILCOR Advisory Statement, October 2002. PMID- 17355668 TI - Nurse practitioners in the ED: a rebuttal. PMID- 17355670 TI - Nurse-initiated, titrated intravenous opioid analgesia reduces time to analgesia for selected painful conditions. AB - OBJECTIVES: Traditionally, patients have to wait until assessed by a physician for opioid analgesia to be administered, which contributes to delays to analgesia. Western Hospital developed a protocol enabling nurses to initiate opioid analgesia prior to medical assessment for selected conditions. The aim of this study was to determine the impact of this protocol on time to first opioid dose in patients presenting to the emergency department (ED) with renal or biliary colic. METHODS: This was an explicit medical record review of all adult patients with an ED discharge diagnosis of renal or biliary colic presenting to a metropolitan teaching hospital ED. Patients were identified via the ED data management system. Data collected included demographics, condition, triage category, time of presentation, whether analgesia was nurse-initiated or not, and interval from arrival to first opioid analgesic dose. The narcotic drug register for the relevant period was also searched to cross-check whether opiates were doctor- or nurse-initiated. RESULTS: There were 58 presentations in the nurse initiated opioid analgesia group and 99 in the non-nurse-initiated analgesia group. Groups were reasonably well matched for gender, triage category and time of presentation, but there was a higher proportion of biliary colic in the non nurse-initiated analgesia group. Median time to first analgesic dose was 31 minutes in the nurse-initiated group and 57 minutes in the non-nurse-initiated analgesia group (effect size, 26 minutes; 95% confidence interval 16-36 min; p < 0.0001]. There were no major adverse events in either group. CONCLUSION: A nurse initiated opioid analgesia protocol reduces delays to opioid analgesia for patients with renal and biliary colic. PMID- 17355671 TI - Maintaining continuity of care: a look at the quality of communication between Ontario emergency departments and community physicians. AB - BACKGROUND: To maintain continuity of care when a patient's care is transferred between physicians, continuity of patient information is required. This survey determined how, and how well, Ontario emergency departments (EDs) communicate patient information to physicians in the community. METHODS: We surveyed Ontario ED chiefs to determine the most common media and methods used for disseminating information. We measured the perceived quality of their system, which was regressed against the hospital teaching status and community size using generalized logits modelling. Finally, we elicited the components of an ideal communication system for the ED. RESULTS: One hundred and forty-three (85.6%) Ontario ED chiefs participated. The ED record of treatment was the most commonly used medium (95%). Postal service was the most common (55%) method of disseminating information. Thirty-three chiefs (23%) perceived the quality of communicating patient information from their ED as unsatisfactory or inadequate. This perception was significantly more prevalent in larger communities (excellent v. unsatisfactory [odds ratio (OR) 44.9, 95% confidence interval (CI) 13.9-140] and satisfactory v. unsatisfactory [OR 2.9, 95% CI 1.6-5.1]) and in teaching hospitals (satisfactory v. unsatisfactory [OR 9.7, 95% CI 4.7-20.3]). Seventy eight percent of responding chiefs felt that patient information should be disseminated using electronic means, either through email or server access. CONCLUSIONS: To communicate patient information to community physicians, Ontario ED chiefs report that a copy of the ED record of treatment is sent by postal service. More than one-fifth of ED chiefs perceived communication from their department as unsatisfactory or inadequate. Studies that assess the completeness and accuracy of the record of treatment are required as a first step for measuring the quality of patient information communication in the Ontario ED system. PMID- 17355672 TI - SARS assessment clinic: a rapid response to an infectious outbreak. AB - The Toronto SARS outbreak began in February 2003 and lasted more than 16 weeks. The city and its health care system faced enormous challenges in responding to this new infectious disease, learning about its transmission, diagnosis and treatment, in containing its spread and in coping with its socioeconomic impact. As the site of a significant cluster of cases in the second wave of the outbreak, North York General Hospital (NYGH) quickly adapted many components of its operations, focusing on the fight against SARS. In order to assess potential SARS cases in a safe, efficient and effective manner, NYGH established a SARS assessment clinic. We describe the design features, construction, layout and operation of this clinic. This type of clinic can be rapidly deployed and may be of great value during future infectious outbreaks, including pandemic influenza. PMID- 17355673 TI - Atraumatic hemopericardium in a patient receiving warfarin therapy for a pulmonary embolus. AB - Acute pericardial tamponade is a potentially life-threatening condition that requires immediate treatment. This report describes a patient who presented to the emergency department with an acute hemopericardium and echocardiographic evidence of cardiac tamponade following the initiation of warfarin therapy for a recently diagnosed pulmonary embolism. The association between cardiac tamponade, oral anticoagulation and pulmonary thromboembolic disease is briefly discussed. PMID- 17355674 TI - Using local epidemiology to make a difficult diagnosis: a case of blastomycosis. AB - An otherwise well 21-year-old man from Northwestern Ontario presented to our emergency department in Winnipeg, Manitoba, with a 2-month history of cough, progressively increasing dyspnea, hemoptysis and a 15-kg weight loss. His symptoms were worsening despite antibiotic treatment for presumed bacterial pneumonia. His past history included work as a seasonal labourer clearing brush. He was not hypoxic on room air, but his chest radiograph revealed a miliary pattern and bilateral infiltrates. A Mantoux test for tuberculosis was non reactive, and the sputum gram stain was unremarkable. Empiric therapy was initiated for blastomycosis and the diagnosis was confirmed with a calcofluor stain of the sputum. Although blastomycosis is rare in most regions in North America, there is an unusually high incidence of blastomycosis in Northwestern Ontario. This case highlights the intolerance and utility of knowledge of the local epidemiology in establishing difficult diagnoses of regional importance, such as fungal pneumonias. PMID- 17355675 TI - Children and magnet-backed jewellery. PMID- 17355676 TI - Sepsis therapy in the next decade: seamless care from emergency to the ICU. PMID- 17355677 TI - Treatment failure in emergency department patients with cellulitis. AB - OBJECTIVE: To identify the rate of treatment failure in emergency department patients with cellulitis. METHODS: This prospective observational convenience study enrolled adult patients with uncomplicated cellulitis. Physicians performed a standardized assessment prior to treatment. To calculate the interrater reliability of the assessment, duplicate data collection forms were completed on a small subsample of patients. Treatment failure was defined as the occurrence of any one of the following events after the initial emergency department visit: incision and drainage of abscess; change in antibiotics (not due to allergy/intolerance); specialist consultation; or, hospital admission. Comparison of means and proportions between the 2 groups was performed with univariate associations, using parametric or non-parametric tests where appropriate. RESULTS: Seventy-five patients were enrolled; 57% were male, the mean age was 48 (standard deviation 19), 71 (95%) patients had extremity cellulitis and 10 (13%) had abscess with cellulitis. Fourteen episodes (18.7%, 95% confidence interval [CI] 11%-28%) were classified as treatment failures, with an oral antibiotic failure rate of 6.8% (95% CI 2%-22%) and an emergency department-based intravenous antibiotic failure rate of 26.1% (95% CI 16%-40%). Patients with treatment failure were older (mean age 59 yr v. 46 yr, p = 0.02) and more likely to have been taking oral antibiotics at enrollment (50% v. 16.4%, p = 0.01). Patients with a larger surface area of infection were also more likely to fail treatment (465.1 cm2 v. 101.5 cm2, p < 0.01). Interrater agreement was high for the presence of fever (kappa 1.0) and the size of surface area of infection (intraclass correlation coefficient 0.98), but low for assessments of both severity (kappa 0.35) and need for admission (kappa 0.46). CONCLUSIONS: The treatment of cellulitis with daily emergency department-based intravenous antibiotics has a failure rate of more than 25% in our centre. Cellulitis patients with a larger surface area of infection and previous (failed) oral therapy are more likely to fail treatment. Further research should focus on defining eligibility for treatment with emergency department-based intravenous antibiotics. PMID- 17355678 TI - Cellulitis: getting it right. PMID- 17355679 TI - Comparison views to diagnose elbow injuries in children: a survey of Canadian non pediatric emergency physicians. AB - OBJECTIVES: Elbow injuries in children are a common presenting complaint to the emergency department. Although radiography is a valuable tool in the diagnosis of this injury, x-rays of the injured elbow are inherently difficult to interpret. As a result, comparison views of the uninjured arm have traditionally been recommended to provide an anatomically "normal" radiograph. Recent studies have questioned the use of comparison views in the pediatric emergency department. The primary objective of this study was to determine current practices of non pediatric emergency physicians in the use of comparison views for the diagnosis of elbow injuries in children. METHODS: A self-administered mail survey was sent to 300 randomly selected emergency physicians, using the Canadian Association of Emergency Physicians database. RESULTS: Two hundred and forty-two (81%) responses were received; 26 were excluded based on pre-determined criteria. Of eligible respondents, 95% ordered comparison views selectively and 64% of these physicians ordered comparison views infrequently. Eighty-eight percent found the comparison views to be "rarely" to "sometimes" useful. Forty-seven percent of respondents stated that they were only "somewhat" confident when interpreting x-rays of a child's elbow. CONCLUSION: This survey demonstrates that non-pediatric emergency physicians are using comparison views selectively for elbow injuries in children, despite being only "somewhat" confident in interpreting the x-rays. PMID- 17355680 TI - Clinical research in the emergency department conducted by non-emergency physicians: potential problems and proposed recommendations. PMID- 17355681 TI - What happens to my patients? An automated linkage between emergency department and mortality data. AB - A simple application linking mortality data from the Bureau of Vital Statistics with data from the emergency department information system is described. This application has been used to supplement the regular mortality review process, identify deaths of patients who left without being seen, and perform outcome studies looking at specified clinical conditions. PMID- 17355682 TI - Variation in emergency department visits for conditions that may be treated in alternative primary care settings. AB - The purpose of this report is to examine Ontario's geographic variation in emergency department (ED) visits for conditions that may be treated in alternative primary care settings. We studied all visits to Ontario EDs in 2002/03 and calculated county-specific age-standardized rates. Overall in Ontario, there were 3174 ED visits per 100,000 population aged 1-74 for conditions that could be treated in alternate primary care settings, but rates varied widely across counties. They were higher in rural counties with rates up to 7-fold higher than the provincial average. Urban counties had lower rates, some were less than one-third of the provincial average. Further research is needed to determine the relationship between ED utilization and primary care capacity. PMID- 17355683 TI - Hyperbaric oxygen therapy in the management of two cases of hydrogen sulfide toxicity from liquid manure. AB - Hydrogen sulfide is a potent lethal gas. Supportive care, nitrite therapy and hyperbaric oxygen are the treatment modalities reported in the literature in cases of hydrogen sulfide exposure. We describe an industrial exposure in which 6 workers inhaled high concentrations of hydrogen sulfide when they entered a closed spreader tank partially filled with liquid swine manure. Five of the 6 lost consciousness, and 2 were agitated and poorly responsive on arrival to the emergency department despite having already received high-flow oxygen for nearly 1 hour. These 2 patients received nitrite therapy followed by orotracheal intubation and hyperbaric oxygen. All patients were discharged home without sequelae after short stays in hospital. The emergency management of hydrogen sulfide exposure is briefly reviewed. PMID- 17355684 TI - Myth: Intravenous amiodarone is safe in patients with atrial fibrillation and Wolff-Parkinson-White syndrome in the emergency department. AB - Wolff-Parkinson-White (WPW) syndrome with atrial fibrillation (AF) is a potentially life-threatening problem requiring rapid conversion to sinus rhythm. The most recent American Heart Association guidelines for the treatment of patients with WPW, published in conjunction with the 2000 Advanced Cardiac Life Support (ACLS) guidelines, suggests that intravenous amiodarone is a first-line therapy for AF-WPW; however the evidence suggests this is a potentially dangerous myth. PMID- 17355685 TI - Diagnostic uncertainty in a case of neuroleptic malignant syndrome. AB - Neuroleptic malignant syndrome (NMS) is a potentially life-threatening condition that has been associated with antipsychotic use. Most diagnostic criteria include fever and muscle rigidity, although NMS may present without either. Diagnostic uncertainty in such cases may result in delays in diagnosis and management, leading to adverse consequences for these patients. The differential diagnosis of NMS is broad and includes a number of neurological, medical and psychiatric conditions as well as substance and medication-induced disorders. A case is described that illustrates an atypical presentation of NMS and demonstrates some of the challenges in its diagnosis. Limitations of current NMS criteria are also examined, and suggestions for future criteria are presented. PMID- 17355686 TI - Tunnelled central venous catheter-induced thrombosis: a rare case of superior vena cava syndrome. AB - Thrombotic venous obstruction in patients with a tunnelled central venous catheter is a cause of superior vena cava syndrome that is not routinely encountered by emergency physicians. Diagnosis requires identifying patients at risk (e.g., those under treatment for cancer and those who have a tunnelled central venous catheter), recognizing the signs and symptoms of superior vena cava syndrome, usually dyspnea and dilated neck or thoracic veins, and imaging the venous obstruction using computer tomography or sonography. Management involves anticoagulation and local thrombolytic administration. We report the case of a 28-year-old woman who presented with a 2-day history of face, chest and bilateral arm swelling who had been receiving maintenance chemotherapy for acute lymphoblastic leukemia through a Hickman catheter. This case demonstrates the need to be vigilant for thrombus formation in patients with long-term, indwelling central venous catheters. PMID- 17355687 TI - Nail embolization to the femoral artery. AB - Modern air-nailing tools are known to cause penetrating trauma. We report the unusual case of a pneumatically fired carpenter's nail that penetrated the chest of a 30-year-old man and subsequently embolized from the heart to the left femoral artery without clinical evidence of having entered the heart. The nail was surgically removed, and the patient was discharged from hospital without sequelae after 10 days. This case and the relevant literature are discussed from the perspective of the emergency department investigation and care of such patients. PMID- 17355688 TI - Something's not right. PMID- 17355690 TI - Prospective time study derivation of emergency physician workload predictors. AB - BACKGROUND: A reliable emergency department (ED) workload measurement tool would provide a method of quantifying clinical productivity for performance evaluation and physician incentive programs; it would enable health administrators to measure ED outputs; and it could provide the basis for an equitable formula to estimate ED physician staffing requirements. Our objectives were to identify predictors that correlate with physician time needed to treat patients and to develop a multivariable model to predict physician workload. METHODS: During 31 day, evening, night and weekend shifts, a research assistant (RA) shadowed 20 emergency physicians, documenting time spent performing clinical and non-clinical functions for 585 patient visits. The RA recorded key predictors including patient gender, age, vital signs and Glasgow Coma Scale (GCS) score, and the mode of arrival, triage level assigned, comorbidity and procedures performed. Multiple linear regression was used to describe the associations between predictor variables and total physician time per patient visit (TPPV), and to derive an equation for physician workload. Model derivation was based on 16 shifts and 314 patient visits; model validation was based on 15 shifts and 271 additional patient visits. RESULTS: The strongest predictor variables were: procedure required, triage level, arrival by ambulance, GCS, age, any comorbidity, and number of prior visits. The derived regression equation is: TPPV = 29.7 + 8.6 (procedure required [Yes]) - 3.8 (triage level [1-5]) + 7.1 (ambulance arrival) - 1.1 (GCS [3-15]) + 0.1 (age in years) - 0.05 (n of previous visits) + 3.1 (any comorbidity). This model predicted 31.3% of the variance in physician TPPV (F [12, 29] = 13.2; p < 0.0001). CONCLUSIONS: This study clarifies important determinants of emergency physician workload. If validated in other settings, the predictive formula derived and internally validated here is a potential alternative to current simplistic models based solely on patient volume and perceived acuity. An evidence-based workload estimation tool like that described here could facilitate ED productivity measurement, benchmarking, physician performance evaluation, and provide the substrate for an equitable formula to estimate ED physician staffing requirements. PMID- 17355691 TI - Dog bites in Canadian children: a five-year review of severity and emergency department management. AB - OBJECTIVES: Dog bites are a common problem. The purpose of this study was to determine the characteristics of dog bites and their emergency department management in a Canadian pediatric population, and to provide treatment and prevention recommendations. METHODS: The charts of all children 10 sutures, n = 69), associated fractures (n = 4), operating room repair (n = 21) or fatality (n = 1). The mean age of children with severe bites was significantly lower than children with mild bites (6.3 v. 7.8 yr, p < 0.01). Most patients were treated solely in the emergency department (84.7%, n = 243); however 44 (15.3%) were admitted to hospital and required a total of 144 days of inpatient care. Signs of infection were described in 16 cases (5.6%); of these 8 had received 2 or more prior doses of antibiotics. Public health or police notification was documented in 56 cases (19.5%), and safety or preventive discussion was documented in 3 cases (1.0%). CONCLUSIONS: Dog bites in Canadian children are common, often serious or even lethal, and not always managed ideally. Preventive discussion and public health contact is infrequently documented and likely seldom occurs. In addition to medical care, emergency department staff should provide and document preventive guidance and ensure involvement of public health or police when indicated. PMID- 17355692 TI - A survey of one CCFP-EM program's graduates: their background, intended type of practice and actual practice. AB - OBJECTIVES: Our primary objective was to survey the graduates of one residency program with respect to anticipated versus actual medical practice. METHODS: Using a modified Dillman technique, we surveyed all 83 physicians who had completed one year of residency training that led to certification of special competency in Emergency Medicine (CCFP-EM) at the University of Western Ontario (UWO) from 1982-2004. Respondents were asked what type of medicine they had thought they would practise before beginning their emergency medicine training. They were then asked to describe their employment from graduation to present time. Additional demographic information was collected. Correlation between demographic factors and other selected factors of influence upon career decisions was analyzed. RESULTS: Our response rate was 87% (72/83), with 71% (51/72) respondents being male. At the start of their CCFP-EM residency training, 50% of respondents intended to practise emergency medicine exclusively and 47% intended to blend family and emergency medicine. For each of the respondents' first 4 positions of employment, the greatest percentage were practising emergency medicine only (ranging from 72% in position 1 to 53% in position 4), while the number engaging in a blended family/emergency medicine practice never exceeded 20%. No demographic factors surveyed had significant correlation with intended or actual practice. In all positions of employment, "type of practice" was ranked as the most influential factor in choosing that position. CONCLUSION: Most graduates of the UWO CCFP-EM program practise in emergency medicine only positions. Less than 20% are engaged in a blended family/emergency medicine practice. At training onset, one-half of the residents intended to practise emergency medicine exclusively. None of the demographic factors surveyed significantly correlated with intended or actual practice. Further examination of the practice patterns of all emergency medicine residency program graduates is an essential part of future planning for the specialty of Emergency Medicine in Canada. PMID- 17355693 TI - Faculty perceptions and practice impact of a faculty development workshop on emergency medicine teaching. AB - BACKGROUND: Faculty development initiatives to improve emergency department (ED) teaching are compromised by the paucity of information about what behaviours and characteristics are desirable in an emergency medicine (EM) teacher. OBJECTIVES: To design and evaluate a learner-centred, interactive faculty development workshop based on original ED teaching research. METHODS: Registrants for a university-based faculty development workshop on ED teaching completed a needs assessment and pre-workshop self-reflection exercise. Responses were grouped into 3 themes derived from the ambulatory teaching literature and a recent survey of expert clinical EM teachers and learners. Participants underwent a half-day workshop consisting of 1 large group interactive session and 3 small group sessions using role playing, practice reflection, real time review of hard copy resources, and brainstorming. Evaluation included a post-event ordinal scale questionnaire and a 4-month follow-up short answer survey, both measuring participants' perceptions of workshop effectiveness. RESULTS: Fifteen faculty participated. The needs assessment identified "Common mistakes," "Teaching efficiently" and "Dealing with the difficult learner" as themes. All 15 completed evaluations, rating the workshop as relevant (4.6/5), specific to their needs (4.4/5) and useful (4.5/5). At 4 months, 10 out of 10 respondents reported success at implementing new techniques and 8 reported greater confidence in teaching. The most common new techniques were: setting better learning objectives, giving better feedback, actively seeking teaching opportunities, and identifying a teaching point. CONCLUSIONS: Learner-centred faculty development meets perceived needs of faculty and can result in participants trying new teaching strategies. PMID- 17355694 TI - Needed: a commitment to basic training in emergency medicine teaching. PMID- 17355695 TI - Emergency preparedness: what every health care worker needs to know. AB - Canada is moving forward quickly with plans to ensure that it is prepared to deal with emergencies. The National Framework for Health Emergency Management, released Nov. 26, 2004, recommends that a National Health Incident Management System (IMS) be developed. However, although most communities have successfully implemented IMS in the emergency services sector, many are still struggling with the integration of IMS into their health care systems. It is essential that all health care workers, regardless of profession or position, understand at least the basic concepts of emergency preparedness because of the wide variety of roles they may be asked to fulfill in an emergency situation. This article will review the basic concepts in emergency preparedness and management with a specific focus on IMS in health care. PMID- 17355696 TI - What are the chances? PMID- 17355697 TI - Emergency medicine in Jamaica. PMID- 17355698 TI - Subspecialization in emergency medicine: where do we go from here? PMID- 17355699 TI - Brugada syndrome in a young patient with palpitations. AB - Brugada syndrome is a potentially lethal and eminently treatable entity that may present with palpitations or syncope. This article presents the case of a young patient with Brugada syndrome and reviews key features in the epidemiology, pathophysiology, diagnosis, treatment and prognosis of this condition. PMID- 17355700 TI - Spinal epidural abscess. AB - Spinal epidural abscess is an uncommon condition. Predisposing factors include spinal surgery, recent trauma, immunosuppression, a distal site of infection and intravenous drug use; however, these are not always present, as illustrated by this case report describing a patient who had repeated emergency department visits and delayed diagnosis that was ultimately confirmed via magnetic resonance imaging. PMID- 17355702 TI - Successful implementation of a combined pneumococcal and influenza vaccination program in a Canadian emergency department. AB - OBJECTIVES: To determine the proportion of patients vaccinated with pneumococcal (PVAX) and influenza (IVAX) vaccines under an emergency department (ED) vaccination program, that would not otherwise have been vaccinated by other primary care resources. METHODS: This prospective cohort study was performed in a tertiary care academic centre. A questionnaire was administered to all consenting ED patients who met screening eligibility criteria to receive either IVAX or PVAX. Eligible unvaccinated patients who did not plan on receiving vaccination elsewhere were offered one or both of the vaccines and, if agreeable, were immunized in the ED. RESULTS: During the 4-week study period, 754 patients (36% of all presenting ED patients) were eligible for vaccination with one or both vaccines. Of these 525 (70%) consented to participate in the study and completed a questionnaire. Of the 525 participants, 289 (55% of IVAX eligible patients; 95% confidence interval [CI], 51%-59%) were unvaccinated against influenza that year and did not plan on being vaccinated elsewhere and 277 (60% of PVAX eligible patients; 95% CI, 56%-64%) were unvaccinated against pneumococcus and did not plan on being vaccinated elsewhere. IVAX was administered to 187 patients (65% penetration; 95% CI, 59%-70%), and PVAX was administered to 165 patients (60% penetration; 95% CI, 54%-65%). Overall vaccine penetration was 46% (95% CI, 42% 50%) in the study participants and 32% (95% CI, 29%-35%) for the entire ED screened and eligible group. Reasons for vaccination refusal included concerns about benefit, side effects, and the desire to discuss vaccination with their primary care physician. CONCLUSIONS: An ED-based program can result in the vaccination of a significant proportion of patients eligible for IVAX and/or PVAX who would otherwise likely go unprotected. PMID- 17355703 TI - Pre-hospital torso-warming modalities for severe hypothermia: a comparative study using a human model. AB - OBJECTIVE: To compare 5 active torso-warming modalities in a human model of severe hypothermia with shivering heat production inhibited by intravenous meperidine. METHODS: Six subjects were cooled on 6 different occasions each, in 8 degrees C water, for 30 minutes or to a core temperature of 35 degrees C. Spontaneous warming was the first torso-warming modality to be tested for every subject, and results served both as a comparative control and for determination of the meperidine dose for subsequent trials. Meperidine (1.5 mg/kg) was administered during the final 10 minutes of immersion to suppress shivering. Subjects were removed from the water, dried and insulated for 30 minutes, followed by 120 minutes of 1) forced-air warming with either a 600-W heater and commercial soft warming blanket; or 2) a 600-W heater and rigid cover; or 3) an 850-W heater and rigid cover; or 4) a charcoal heater on the chest; or 5) direct body-to-body contact with a normothermic partner. Supplemental meperidine (to a maximum cumulative dose of 3.2 mg/kg) was administered as required to inhibit shivering. RESULTS: The initial post-cooling afterdrop was approximately 1.0 degrees C. After 30 minutes, core temperature continued to drop by 0.45 degrees C in spontaneous and body-to-body warming modalities. This post-warming afterdrop was significantly less with 600-W heater and rigid cover and the charcoal heater (0.26 degrees C) and the least with 850-W heater and rigid cover (0.17 degrees C). Core rewarming rates were highest using 850-W heater and rigid cover (1.45 degrees C/hr), with charcoal heating and 600-W rigid heater (0.7 degrees C/hr), 600-W heater and blanket (0.57 degrees C/hr) and body-to-body warming (0.52 degrees C/hr) being more effective than spontaneous warming (0.36 degrees C/hr). CONCLUSIONS: In non-shivering subjects, external heat application was effective in attenuating core temperature afterdrop and facilitating safe core rewarming; this was more evident when heat was delivered preferentially to the chest, and dependent upon the amount of heat donated. The modalities studied appear sufficiently practical and portable for pre-hospital use and should be considered for such situations, particularly in rural or wilderness locations where anticipated transport time to the hospital exceeds 30 minutes. PMID- 17355704 TI - Adult epiglottitis: a five-year retrospective chart review in a major urban centre. AB - OBJECTIVE: There is an increasing awareness of unvaccinated adults presenting with epiglottitis to the emergency department. This study examines the clinical presentations and outcomes of diagnosed cases of adult epiglottitis presenting to all emergency departments in Hamilton, Ont., between 1999 and 2003. METHODS: We employed explicit protocols with defined variables, trained abstractors and standardized abstraction forms, and reviewed all diagnosed cases of adult epiglottitis during a 5-year period. Inter-rater agreement was measured using a kappa statistic. RESULTS: Inter-rater reliability for data abstraction was kappa = 1. From a total of 1 million emergency department admissions, 54 cases of epiglottitis were identified. The mean age was 49, and 69% of the patients were male. The 3 most frequently documented symptoms were sore throat (100%) odynophagia (94%) and inability to swallow secretions (63%). The 2 most frequently documented signs were swelling of the epiglottis/supraglottis (100%), and tachycardia (53%). Organisms were isolated from blood in 11% of the cases. There was a white blood cell count >20 x 10(9)/L in 4 of the cases (7.4%). From the 54 cases, 9 of the patients were intubated and all patients were safely discharged from hospital. CONCLUSION: Adults presenting with epiglottitis to the emergency department in Hamilton have good outcomes, with less airway management required than previously reported in children. Further study is needed to see if these conclusions are similar in other populations. PMID- 17355705 TI - Effect of frequent water immersion on the rate of tissue adhesive sloughing: a randomized study. AB - OBJECTIVES: Frequent soaking of lacerations closed with tissue adhesives is not recommended for fear of premature adhesive sloughing and wound dehiscence. This recommendation is based on studies of sutured lacerations, and may not be directly relevant to wounds closed with tissue adhesives. The objective of our study was to determine whether frequent soaking of octylcyanoacrylate would result in premature sloughing of the adhesive. METHODS: This randomized controlled study enrolled healthy volunteers between 10 and 65 years of age. All subjects had 0.5 mL of low viscosity octylcyanoacrylate applied in two 4-cm lines made on intact skin on both of the subjects' forearms. One arm was randomized to daily immersion in soapy water; the other arm served as a control. The primary outcome was the area of remaining adhesive, which was traced and calculated daily until complete sloughing, and expressed as percent slough. Kaplan-Meier survival curves were constructed and compared using log-rank tests. A Wilcoxon's signed rank test to account for paired sample design was also used. RESULTS: We enrolled 20 subjects, 12 female and 8 male, with a mean age of 32 years (range, 10-62 yr). Mean time until complete sloughing in control and immersed arms was 5.2 and 4.2 days, respectively, with a mean difference of 1.0 days (95% confidence interval, 0.2 to 1.8; p = 0.01). CONCLUSIONS: Daily immersion accelerates the sloughing of low viscosity octylcyanoacrylate applied to intact skin. PMID- 17355706 TI - Disaster medicine education in Canadian medical schools before and after September 11, 2001. AB - OBJECTIVE: To describe disaster medicine (DM) education in 16 Canadian medical schools before and after September 11, 2001 (9/11). METHODS: Email invitations and reminders to complete an Internet-based survey were sent to 48 undergraduate and fellowship representatives. RESULTS: A total of 24 responses were received from 15 of the 16 Canadian medical schools in operation at the time of the study, representing 10 undergraduate and 14 fellowship programs. Prior to 9/11, 22 programs at 9 schools taught DM compared with 14 programs post 9/11, a reduction of 37%. Six schools reported no DM teaching before 9/11; 7 reported no DM instruction after that date. Respondents from 12 schools felt that DM should be taught at the undergraduate level, and 9 of the 12 felt it should be included as core content. Respondents from all 15 responding schools felt that DM should be included as core content at the fellowship level. Twenty-two respondents (92%) indicated a belief that the public expects physicians to be prepared to deal with the consequences of disasters. The most frequently taught topics were emergency medical services and disasters, disaster management, hospital disaster planning, and bioterrorism. CONCLUSION: Despite support for DM instruction and increases in terrorism and global disasters, 46% of the responding medical schools do not teach this topic and there has been a downward trend in this regard since 9/11. PMID- 17355707 TI - A Canadian fellowship training program in emergency medical services. AB - Emergency medical services (EMS) is increasingly recognized to be an integral part of the health care system. Given the expanding role and scope of EMS, there is need for structured education of emergency physicians interested in pursuing subspecialization in EMS. In 2001, a group of academic emergency specialists at the University of Toronto developed the first Canadian EMS Fellowship Program. This paper describes the development, current status, and future directions of this Program. The University of Toronto EMS Fellowship Program may serve as a template for the development of similar programs elsewhere in Canada and internationally. PMID- 17355708 TI - Attracting top residency candidates: a survey of important program attributes. AB - OBJECTIVES: Emergency medicine (EM) residents work intimately with emergency department staff, and many residents become staff at the institutions that train them. As such, it is in the interest of all training sites to attract the strongest candidates to their programs. The goal of this study was to determine what factors make programs most appealing to EM residency applicants. METHODS: A survey was developed to assess the relative importance of 20 factors used by EM residency applicants in selecting a Royal College of Physicians and Surgeons of Canada residency program. The survey was piloted on 17 University of Western Ontario EM residency candidates in 2003, and validated on 26 EM residency candidates applying to 8 sites across Canada in 2004. RESULTS: The 20 surveyed factors fell into 4 categories. The most important factors were those relating to interactions with the program (4.5 out of 5), followed by factors relating to the program itself (3.5), personal factors (3.4), and lastly, factors relating to the city/province (2.9). CONCLUSIONS: These data suggest that the most important factors are "interactions with a program" and program characteristics. Both of these are largely within a program's control. By striving to make their curriculum, interview days and medical student electives more appealing a residency program can improve its ability to attract the strongest residency candidates. PMID- 17355709 TI - Reflections on ACLS. PMID- 17355710 TI - Orf in humans: dramatic but benign. AB - Orf is a parapoxvirus infection of sheep and goats that causes blistering lesions on the lips, nostrils, udders or toes of affected animals. Human contact can cause transmission by direct inoculation. Human orf has typically been confined to rural settings. A case is presented of an immigrant African inner-city housewife who contracted the disease after preparing a sheep's head for a meal. The lesions resolved completely after 1 month without treatment. Although relatively rare and benign, this infection is probably under-reported and over treated in this country. This case highlights the fact that urban physicians can expect to encounter once rare or solely rural-based infections with increasing frequency. PMID- 17355711 TI - Paralysis: a rare presentation of abdominal aortic aneurysm thrombosis. AB - We report an acute thrombosis of an abdominal aortic aneurysm presenting with paralysis of a lower extremity. The usual presentation of such thrombosis is vascular compromise of the lower extremities. When the thrombus obstructs the artery of Adamkiewicz, the main blood supply to the lower spinal cord, spinal ischemia and paralysis can occur. Mechanisms of aortic occlusion and treatment of aortic thrombosis are briefly outlined. PMID- 17355712 TI - Intra-articular lidocaine for the reduction of posterior shoulder dislocation. AB - Anterior shoulder dislocations are the most common major joint dislocation seen in emergency departments. Intra-articular lidocaine is a useful method of analgesia for facilitating the reduction of anterior shoulder dislocations. Posterior shoulder dislocations represent a small minority of shoulder dislocations. We present the case of a posterior shoulder reduction in an elderly female whose reduction was performed following the intra-articular injection of lidocaine. Intra-articular lidocaine represents a useful alternative to facilitate the reduction of shoulder dislocations, particularly in patients at higher risk for complications from sedation. PMID- 17355713 TI - Mummy days: balancing doctoring and mothering. PMID- 17355714 TI - National review course in emergency medicine. PMID- 17355715 TI - CAEP 2005 Edmonton: Resident Awards. PMID- 17355716 TI - The staff are your friends: intellectually disabled identities in official discourse and interactional practice. AB - Talk between care staff and people with learning disabilities may reveal a conflict between official policy and actual social practice. We explore a case in which care staff are in the process of soliciting residents' views on 'relationships'. Ostensibly, this is an empowering part of a group meeting, meant to help the residents understand their relationships with the people around them, and to value those which are positive. However, the talk mutates from solicitation to instruction and, in doing so, provides a vivid case of people with learning disabilities being attributed social rights more limited than is consistent with institutional service policy. We unpack the play of category membership in this episode to illustrate how conflicting agendas can lead to the construction, even in ostensibly empowering encounters, of identities actively disavowed at the level of official discourse. PMID- 17355717 TI - Attitudes, personal evaluations, cognitive evaluation and interpersonal attraction: on the direct, indirect and reverse-causal effects. AB - The authors hypothesized that (1) attraction toward a stranger based on attitudinal similarity is automatic, but cognitive evaluation of the stranger's quality before the measurement of attraction can make attraction nonautomatic or controlled; (2) personal evaluations from the stranger activate automatic attraction and cognitive evaluation; (3) controlled attraction from attitudes and automatic attraction and cognitive evaluation from personal evaluations engender reverse-causal effects (i.e. they mediate each other); and (4) attraction and cognitive evaluation are distinct constructs. Attitudinal similarity between the participant and the stranger or personal evaluations of the former by the latter were varied in Experiment 1 (N=96), and were crossed with each other in Experiment 2 (N=240). Orders of response measurement were either cognitive evaluation followed by attraction or attraction followed by cognitive evaluation. Results confirmed the hypotheses. Implications of the findings are discussed. PMID- 17355718 TI - Simulating behaviour change interventions based on the theory of planned behaviour: Impacts on intention and action. AB - The theory of planned behaviour (TPB; Ajzen, 1991) has been used extensively to predict social and health behaviours. However, a critical test of the TPB is whether interventions that increased scores on the theory's predictors would engender behaviour change. The present research deployed a novel technique in order to provide this test. Statistical simulations were conducted on data for 30 behaviours (N=211) that estimated the impact of interventions that generated maximum positive changes in attitudes, subjective norms and perceived behavioural control (PBC) on subsequent intentions and behaviour. Findings indicated that interventions that maximized TPB variables had a substantial impact on behavioural intentions. Although TPB maximization increased the proportion of the sample that performed respective behaviours by 28% compared with baseline, the behaviour of a substantial minority of the sample (26%) did not change. The research also identified several interactions among TPB variables in predicting simulated intention and behaviour scores and investigated the mediating role of intentions in predicting behaviour. PMID- 17355719 TI - Using the theory of planned behaviour to predict observed driving behaviour. AB - The ability of psychosocial variables to predict driver behaviour was tested using the theory of planned behaviour (TPB; I. Ajzen, 1985) as a theoretical framework. At Time 1, participants (N=150) completed questionnaire measures of TPB variables. 1 week later, participants' behaviour was assessed using both self reports and observations of driving speed derived from a high-fidelity driving simulator. Multiple regression analyses demonstrated that: (a) the TPB was a strong predictor of drivers' intentions and self-reported speeding behaviour, and (b) intention was the sole predictor of observed speeding behaviour. Standard and repeated events survival analyses showed that intention also predicted the maintenance of drivers' compliance with speed limits. The discussion focuses on the TPB's relationships with observed and self-reported behaviour, and the implications for designing interventions. PMID- 17355720 TI - Identity motives and in-group favouritism: a new approach to individual differences in intergroup discrimination. AB - Theories suggest that identity motives for self-esteem, meaning, distinctiveness and belonging are implicated in intergroup discrimination. Experimental studies have supported predictions, but correlational tests have been hindered by methodological problems. Using a new approach to measuring identity motives, we compared predictions of individual differences in in-group favouritism. Seventy British adults completed measures of identity motives, British identification and positive and negative trait typicality ratings of British and German nationalities. With greater identification, the strength of motives for distinctiveness and belonging increasingly predicted in-group favouritism: consistent with optimal distinctiveness theory, the belonging motive predicted positive ratings of the national in-group, whereas the distinctiveness motive predicted negative ratings of the national out-group. Results show the value of disentangling measures of motive strength from measures of motive satisfaction. PMID- 17355721 TI - Memory for stereotype (in)consistent information: the role of in-group identification. AB - Effects of identification with one's group on memory of stereotype consistent and inconsistent information about one's group were examined in two studies. In the first study, we focused on supporters of a low status soccer team, and observed that die-hard fans were more likely to remember stereotype-inconsistent results of their team than fair-weather fans. This pattern was replicated in a second study, which was executed among supporters of a high status soccer team. We discuss the implications of these results for the role of motivational factors such as in-group identification in cognitive social psychology. PMID- 17355722 TI - Group member prototypicality and intergroup negotiation: how one's standing in the group affects negotiation behaviour. AB - How does a representative's position in the group influence behaviour in intergroup negotiation? Applying insights from the social identity approach (specifically self-categorization theory), the effects of group member prototypicality, accountability and group attractiveness on competitiveness in intergroup bargaining were examined. As representatives of their group, participants engaged in a computer-mediated negotiation with a simulated out group opponent. In Experiment 1 (N=114), representatives with a peripheral status in the group sent more competitive and fewer cooperative messages to the opponent than did prototypical representatives, but only under accountability. Experiment 2 (N=110) replicated this finding, and showed that, under accountability, peripherals also made higher demands than did prototypicals, but only when group membership was perceived as attractive. Results are discussed in relation to impression management and strategic behaviour. PMID- 17355723 TI - Predictors and consequences of negative attitudes toward immigrants in Belgium and Turkey: the role of acculturation preferences and economic competition. AB - This research tested predictors and consequences of majority members' negative attitudes towards immigrants in Belgium and Turkey. It tested a mediation model in which economic competition and a perceived preference of the immigrants for culture maintenance have negative effects on majority members' own acculturation preference for integration, and where a perceived preference of the immigrants for contact has a positive effect. The effects of all three predictors were hypothesized to be mediated by negative attitudes toward immigrants. Two survey studies were conducted, one in Belgium (N=106) and one in Turkey (N=93). Results showed that, as hypothesized, 'economic competition' and a 'perceived preference for contact' had indirect effects on 'own acculturation preference' for integration, and 'negative attitude' was the mediator. 'Perceived preference for cultural maintenance' had a direct effect on 'own acculturation preference'. PMID- 17355724 TI - Locals, incomers and intra-national migration: place-identities and a Scottish island. AB - In a trans-national context, immigrants are often described as essentially different from existing residents. However these descriptions of group differences are occasioned constructions of immigrants, and talk about nations provides frameworks of history and space within which immigration is understood. Claimed group differences and the proposed commonality of nation together present a challenging context for immigrants to negotiate identities and to gain acceptance. Drawing on the concept of place-identity, we examined here whether similar issues arise in intra-national migration to a remote Scottish island. We conducted semi-structured interviews with individuals who had lived on the island for periods ranging from 14 months to 20 years. The interviewees described island residents as comprising different groups, in terms such as residence, motivation, place of birth, and connections to other locations. The interviewees negotiated place-identities that compared favourably with others with more transitory connections but unfavourably with residents of longer-standing. Findings show that spatial connections can be used to account for varying degrees of social status in such locations. But some issues relevant to trans-national immigration still arise in intra-national migration, even in the absence of racial, ethnic, religious, or language differences. In short, 'incomers' cannot readily do 'being local'. PMID- 17355725 TI - Angry opposition to government redress: when the structurally advantaged perceive themselves as relatively deprived. AB - We examined (structurally advantaged) non-Aborigines' willingness for political action against government redress to (structurally disadvantaged) Aborigines in Australia. We found non-Aborigines opposed to government redress to be high in symbolic racism and to perceive their ingroup as deprived relative to Aborigines. However, only perceived relative deprivation was associated with feelings of group-based anger. In addition, consistent with relative deprivation and emotion theory, it was group-based anger that fully mediated a willingness for political action against government redress. Thus, the specific group-based emotion of anger explained why symbolic racism and relative deprivation promoted a willingness for political action against government redress to a structurally disadvantaged out-group. Theoretical and political implications are discussed. PMID- 17355726 TI - Replenishing connectedness: reminders of social activity reduce aggression after social exclusion. AB - Previous research found that social rejection leads to increased aggression. How can this aggressive behaviour be prevented? Four experiments demonstrate that reminders of social activity reduce aggression after social exclusion. A brief, friendly social connection with an experimenter (versus a neutral interaction) reduced aggression after social rejection. A traditional mood induction had no effect on aggressive behaviour, showing that an activity must be social to be effective. Participants who wrote about a family member, a friend or a favourite celebrity were also not aggressive after rejection. The effect was mediated by trust in other people but not by state self-esteem or mood. Rejected participants who have an alternative source of social connection eschew the increased aggression usually displayed after social exclusion. PMID- 17355727 TI - What is a typical rape? Effects of victim and participant gender in female and male rape perception. AB - The study had three research aims: (1) to examine the current perception of female rape. Given recent changes in public awareness of female rape, it was predicted that respondents would conceptualize a typical female rape as an acquaintance rape rather than as the stranger rape stereotype; (2) to examine whether these perceptions differ according to respondents' gender; (3) to examine the 'cultural lag' theory of male rape, where it was hypothesized that if the public perception of male rape lags behind female rape, then a typical male rape will be conceptualized as the classic stranger rape stereotype. Findings showed that contrary to predictions, a typical female rape was conceptualized according to the stranger rape stereotype. It was also found that instead of lagging behind female rape along the stranger-acquaintance rape dimension, male rape was viewed predominantly in terms of 'other' factors (factors not found on the stranger acquaintance dimension, e.g. victim/rapist sexual orientation, rapist calls victim names), which were erroneous, sexualizing and homophobic. PMID- 17355728 TI - Use of treatment guidelines in clinical decision making in bipolar disorder: a pilot survey of clinicians. AB - OBJECTIVE: With recent attention to the importance of evidence-based medicine in psychiatry, a number of treatment guidelines have emerged to aid clinicians in clinical decision making. The objective of this study was to assess the extent to which such guidelines are used in the treatment of bipolar disorder. METHODS: In November 2005, self-administered questionnaires were sent to 7000 psychiatrists who treat bipolar disorder in their clinical practice. An additional mailing of these questionnaires was done in January 2006 to a different group of 7000 psychiatrists who also treat bipolar disorder in their clinical practice. The first 312 completed surveys were analyzed. Eight questions relevant to clinical usage of, and attitudes toward, existing guidelines were asked. RESULTS: Among the 312 respondents, 64.1% reported making routine use of treatment guidelines when making clinical decisions, including 19.6% who used the American Psychiatric Association treatment guidelines and 33.0% who used all published guidelines. Of those who did not use bipolar guidelines, the most frequently cited reason given by respondents (20.1%) was that such guidelines do not address particular features of their clinical populations. Among the different types of practice, private individual practice gave this answer most frequently (27.5%). CONCLUSIONS: These results suggest that, despite considerable efforts to develop and disseminate evidence-based guidelines, they are not widely implemented and substantial opportunities exist to educate clinicians about their value and relevance. Limitations of the study include a low response rate and possible selection bias. Nonetheless, this project was conceived of as a pilot study and these limitations do not negate the findings, but suggest other avenues for investigation. PMID- 17355729 TI - Verteporfin photodynamic therapy and anti-angiogenic drugs: potential for combination therapy in exudative age-related macular degeneration. AB - OBJECTIVE: To discuss the rationale for combining anti-angiogenic treatment with verteporfin (Visudyne) photodynamic therapy in the management of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and evaluate available evidence for the therapeutic benefits of such approaches. SCOPE: The Medline and EMBASE databases were searched in October 2006 to retrieve relevant articles. Additional articles were obtained from the reference lists of retrieved articles, as well as from recent scientific meetings and company websites. FINDINGS: Treatments for CNV due to AMD can be directed at either the vascular component of CNV (the new vessels that proliferate and leak blood and fluid) or the angiogenic component that leads to the development of the condition. Verteporfin targets the vascular component, whereas anti-angiogenic agents (such as pegaptanib and ranibizumab) target key mediators of the angiogenic cascade. The different mechanisms of action of these approaches offer the potential for additive or synergistic effects with combination therapy. In addition, anti-angiogenic agents might counteract upregulation of angiogenic factors (including VEGF) that occur after verteporfin photodynamic therapy. Results from preclinical and clinical studies of the combination of ranibizumab or pegaptanib with verteporfin warrant continued investigation. CONCLUSIONS: The use of anti-angiogenic agents in combination with verteporfin may have the potential to improve visual outcomes and reduce the number of treatments in eyes with CNV due to AMD, and requires further evaluation in randomized, controlled clinical trials. PMID- 17355730 TI - Race, ethnicity, and use of thiazolidinediones among US adults with diabetes. AB - OBJECTIVE: Significant race and ethnic disparities exist in diabetes-related health care. Using a nationally representative database, we sought to determine if use of thiazolidinediones (TZDs) differs by race and ethnicity. As a secondary objective, we sought to determine if race and ethnicity is associated with use of older oral antidiabetic agents, such as sulfonylureas and metformin. RESEARCH DESIGN AND METHODS: Adult respondents to the 2003 Medical Expenditure Panel Survey with diabetes, identified by diagnosis code or self-report, were included. Race/ethnic groups were defined as: White/not-Hispanic; Black/not-Hispanic; Hispanic; or Other/not-Hispanic. Associations between use of oral antidiabetic agents (defined as > or = 1 prescription for a TZD, sulfonylurea, or metformin) and race/ethnicity, sex, age, insurance status, poverty status, and having a usual source of care were evaluated in univariate analyses with chi(2) tests and in adjusted analyses using logistic regression methods for survey data. RESULTS: A total of 1873 US adults with diabetes were identified, with use of oral antidiabetic agents varying by drug class: 23.1% received TZDs, 45.3% received metformin, and 43.8% received sulfonylureas. Use of oral antidiabetic agents, by drug class, did not differ significantly by race/ethnicity (p = 0.33 for TZDs, p = 0.43 for metformin, p = 0.38 for sulfonylureas). In univariate analyses, only insurance status was significantly associated with use of TZDs (p = 0.03), and no variables were associated with use of sulfonylureas or metformin. In adjusted logistic regression analyses, there were no significant predictors of the use of TZDs or metformin, and only age was significantly associated with the use of sulfonylureas. CONCLUSIONS: In a nationally representative database, fewer US adults with diabetes received TZDs compared with sulfonylureas or metformin in 2003. Although we were not able to differentiate between type 1 and type 2 diabetes, nor did we assess oral agent monotherapy versus combination therapy, we found that use of TZDs, sulfonylureas, and metformin did not differ based on race/ethnicity or other demographic variables such as sex, insurance status, poverty status, or having a usual source of health care. PMID- 17355731 TI - Acute coronary syndromes in Europe: 1-year costs and outcomes. AB - OBJECTIVE: This study aims to estimate costs (including medications prescribed, intervention rates and hospital utilization) and health outcomes of acute coronary syndromes (ACS) during the first year following diagnosis. RESEARCH DESIGN AND METHODS: Treatment pathways for ACS patients were developed and country-specific resource use was multiplied by unit costs. Countries examined were the United Kingdom (UK), France, Germany, Italy and Spain. Patients with unstable angina and acute myocardial infarction (ST-segment elevation and non-ST segment elevation with/without Q-wave) were considered. The study models the incidence of ACS, 1-year mortality, investigations, revascularisation, pharmaceutical use and medical management. Economic outcomes were direct healthcare costs (in 2004 Euros), including total cost, cost per patient with ACS and cost per capita. RESULTS: The estimated number of deaths in the first year following ACS diagnosis ranged from around 22 500 in Spain to over 90 000 in Germany. The largest contributors to total costs are hospital stay and revascularisation procedures. Pharmaceuticals were estimated at 14-25% of ACS total cost. The total cost of ACS in the UK is estimated around 1.9 billion Euros, compared with 1.3 billion Euros in France, 3.3 billion Euros in Germany, 3.1 billion Euros in Italy and 1.0 billion Euros in Spain. The cost per ACS patient ranges from 7009 Euros (in the UK) to 12,086 Euros (Italy). CONCLUSIONS: Countries with higher expenditure on ACS patients tended to have lower case fatality rates, and countries with the lowest incidence of ACS also had the lowest cost per capita. The costs of ACS constitute a large proportion of total healthcare expenditure of Western European economies. PMID- 17355732 TI - Cilastatin protection against cyclosporin A-induced nephrotoxicity: clinical evidence. AB - BACKGROUND: Several studies have documented the nephroprotective effect of cilastatin co-administered with imipenem in subjects treated with cyclosporin A. However, no large clinical studies are available to confirm this observation. Here the quality of the evidence on cilastatin nephroprotection against cyclosporin-induced nephrotoxicity is evaluated. METHODS: The results of all studies where cyclosporin was used alone or combined with imipenem/cilastatin (Tienam) on the same clinical setting were systematically reviewed. Primary outcome was the reduction in serum creatinine concentration. Secondary outcome included development of acute renal failure. Medline was searched using three different retrieval systems (Pubmed, Silver Platter, Knowledge Finder) from January 1966 to February 2006. Attempts were made to contact authors of relevant studies to obtain additional data. Five clinical studies were found, including 125 patients under cyclosporin plus imipenem/cilastatin and 104 under cyclosporin alone. RESULTS: Cyclosporin increased serum creatinine in all the studies. Average reduction of serum creatinine in cilastatin-treated versus untreated patients was Delta = -0.53 mg/dL (95%CI: -0.90 to -0.17) (Z = 2.84, p = 0.004). Variability between studies was large (from Delta = -0.21 to Delta= -1.59 mg/dL) and heterogeneity pronounced (chi(2) = 8.760, df = 4; p = 0.067). Meta-regression of serum creatinine reduction versus baseline serum creatinine explained 84% of this variability, by the variation in basal serum creatinine. When randomized and observational clinical studies were analyzed separately, conclusions were the same: serum creatinine in cilastatin treated patients was reduced by Delta = 0.98 mg/dL (95%CI: -1.57 to -0.38) in randomized studies (Z = 3.213, p = 0.001) and Delta= -0.32 mg/dL (95%CI: -0.63 to -0.01) in observational studies (Z = 2.013, p = 0.044). Odds Ratio for developing acute renal failure was 0.24 (95% CI: 0.11-0.53, p < 0.0001) on patients simultaneously treated with cyclosporin plus imipenem/cilastatin compared to patients treated with cyclosporin alone. CONCLUSIONS: Administration of cilastatin may reduce acute cyclosporin nephrotoxicity. PMID- 17355733 TI - Effects of clarithromycin in patients with active rheumatoid arthritis. AB - OBJECTIVE: To evaluate the clinical efficacy, safety, and tolerability of clarithromycin in patients with rheumatoid arthritis. RESEARCH DESIGN AND METHODS: This was a 6-month, monocenter, randomized, double-blind, placebo controlled study. A total of 81 patients with early rheumatoid arthritis were treated with either once-daily oral clarithromycin (500 mg) or daily oral placebo for 6 months. MAIN OUTCOME MEASURES: The primary efficacy variable was the percentage of patients who had a 20% improvement according to American College of Rheumatology (ACR) criteria (an ACR 20 response) at 6-months. Secondary outcome measures were 50% improvement and 70% improvement according to ACR criteria (an ACR 50 response and an ACR 70 response, respectively). RESULTS: A significantly greater percentage of patients treated with 500 mg clarithromycin met the ACR 20 response at 6 months compared with patients who received placebo (59 vs. 33%; p < 0.001). Greater percentages of patients treated with 500 mg clarithromycin also achieved ACR 50 responses (34 vs. 10%; p < 0.001) and ACR 70 responses (20 vs. 3%; p = 0.003) compared with patients who received placebo, respectively. Clarithromycin was well tolerated. There were no dose-limiting toxic effects. CONCLUSIONS: In patients with early active rheumatoid arthritis, treatment with clarithromycin significantly improved the signs and symptoms of rheumatoid arthritis. Clarithromycin has been shown to be effective against rheumatoid arthritis. PMID- 17355734 TI - Effect of oseltamivir on the risk of pneumonia and use of health care services in children with clinically diagnosed influenza. AB - OBJECTIVE: To evaluate the effectiveness of oseltamivir in reducing the rate of complications of influenza in children. RESEARCH DESIGN AND METHODS: Anonymous, patient-level data from Medstat's MarketScan Research Database between 2000 and 2004 were used to identify children with influenza, aged 1-12 years. Patients who received a prescription for oseltamivir within 1 day of influenza diagnosis were compared with those who received no antiviral therapy. MAIN OUTCOME MEASURES: Primary and secondary study outcomes included occurrence of pneumonia within 14 days of onset of influenza, rates of hospitalization for pneumonia, antibiotic use, numbers of healthcare services utilized, and healthcare expenditures. RESULTS: In total, 4447 (17.9%) children received a prescription for oseltamivir within 1 day of when they were first clinically diagnosed with influenza, and 20 407 (82.1%) children received no antiviral treatment. Overall, children who received oseltamivir for the treatment of physician-diagnosed influenza were 51.7% less likely to be clinically diagnosed with pneumonia at a subsequent medical encounter (relative risk 0.483; 95% CI: 0.326, 0.717). This benefit was associated with reductions in antibiotic use, outpatient and emergency room visits, and savings in outpatient medical expenditures. Net expenditures per patient were not significantly different between children receiving oseltamivir and those who received no antiviral treatment (-$16; 95% CI: -13 dollars , +40 dollars) although pharmacy expenditures were higher. Wide regional variations in oseltamivir use were noted. LIMITATIONS: The study was restricted to patients with employer-sponsored health insurance. The lack of a virologic diagnosis of influenza, and an index date based on the first diagnosis of influenza rather than first exposure or symptom onset, may have resulted in a conservative estimate of treatment effect. CONCLUSIONS: Oseltamivir may reduce the risk of influenza-related morbidity in children when prescribed upon presentation of clinically diagnosed influenza. The use of oseltamivir in children may play an important role in managing influenza outbreaks. PMID- 17355735 TI - Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. AB - OBJECTIVE: To compare the efficacy and tolerability of dronabinol, ondansetron, or the combination for delayed chemotherapy-induced nausea and vomiting (CINV) in a 5-day, double-blind, placebo-controlled study. RESEARCH DESIGN AND METHODS: Patients receiving moderately to highly emetogenic chemotherapy received dexamethasone (20 mg PO), ondansetron (16 mg IV) and either placebo or dronabinol (2.5 mg) prechemotherapy on day 1. Patients randomized to active treatment (dronabinol and/or ondansetron) also received dronabinol (2.5 mg) after chemotherapy on day 1. On day 2, fixed doses of placebo, dronabinol (10 mg), ondansetron (16 mg), or combination therapy were administered. On days 3-5, patients received placebo, flexible doses of dronabinol (10-20 mg), ondansetron (8-16 mg), or dronabinol and ondansetron (10-20 mg dronabinol, 8-16 mg ondansetron). MAIN OUTCOME MEASURES: Total response (TR = nausea intensity <5 mm on visual analog scale, no vomiting/retching, no rescue antiemetic), nausea (occurrence and intensity) and vomiting/retching episodes. RESULTS: Sixty-four patients were randomized; 61 analyzed for efficacy. TR was similar with dronabinol (54%), ondansetron (58%), and combination therapy (47%) versus placebo (20%). Nausea absence was significantly greater in active treatment groups (dronabinol, 71%; ondansetron, 64%; combination therapy, 53%) versus placebo (15%; p < 0.05 vs. placebo for all). Nausea intensity and vomiting/retching were lowest in patients treated with dronabinol. Active treatments were well tolerated. The low number of patients due to slow enrollment limits the interpretation of these data. CONCLUSIONS: Dronabinol or ondansetron was similarly effective for the treatment of CINV. Combination therapy with dronabinol and ondansetron was not more effective than either agent alone. Active treatments were well tolerated. PMID- 17355736 TI - Evaluation of the pharmacokinetics of posaconazole and rifabutin following co administration to healthy men. AB - OBJECTIVE: Posaconazole is a triazole antifungal agent for the treatment and prophylaxis of invasive fungal infections. This non-randomized, open-label, parallel-group, multiple-dose, drug-interaction study was conducted to evaluate the pharmacokinetics of posaconazole and rifabutin following co-administration to healthy subjects. METHODS: Subjects were assigned to treatment groups: Group 1 (posaconazole, 200-mg tablet once daily for 10 days) or Group 2 (rifabutin, 300 mg capsule once daily for 17 days [Days -7 to 10] co-administered with posaconazole, 200 mg tablet once daily for 10 days [Days 1-10]). Posaconazole was administered after rifabutin steady-state was reached. Individual plasma concentration-time data for posaconazole (Day 10, Groups 1 and 2) and rifabutin (Days -1 and 10, Group 2) were analyzed using model-independent methods. RESULTS: Twenty-four men were enrolled in the study. All subjects in Group 1 completed the study; however, four subjects in Group 2 discontinued because of adverse events. When co-administered with rifabutin, posaconazole maximum plasma concentration (C(max)) and area under the plasma concentration-time curve over the dosing interval (AUC([tau])) were reduced 43% (p = 0.005) and 49% (p = 0.008), respectively. Conversely, rifabutin C(max) and AUC([tau]) increased 31% (p = 0.016) and 72% (p < 0.001), respectively, when co-administered with posaconazole. CONCLUSION: Based on the reduced exposure to posaconazole observed in the limited number of subjects in this study and the increased risk for adverse events associated with elevated rifabutin concentrations, concomitant use of rifabutin and posaconazole should be avoided unless the benefit outweighs the risk. PMID- 17355737 TI - Impact of gender on statin efficacy. AB - OBJECTIVE: To determine the impact of statin therapy on the combined endpoint of cardiovascular events in women and men separately. RESEARCH DESIGN AND METHODS: A systematic literature search through May 2006 was conducted to identify randomized, controlled statin trials evaluating the gender specific incidence of cardiovascular events. Weighted averages were reported as relative risks (RRs) with 95% confidence intervals (CI) calculated via random-effects model. MAIN OUTCOME MEASURES: The primary outcome measured was a composite endpoint of all cardiovascular events. Secondary outcomes measured included death, myocardial infarction (MI), and stroke. RESULTS: Fifteen trials were included in this meta analysis. Cardiovascular events were reduced in men (RR 0.76 [95% CI 0.70, 0.81]) and women (RR 0.79 [95% CI 0.69, 0.90]). Reductions in mortality, MI, and stroke predominantly contributed to the reduction in cardiovascular events in men taking statins. Women did not have a reduction in mortality or stroke, suggesting that the reductions in cardiac events may have been predominantly due to reductions in need for revascularization and/or unstable angina. CONCLUSIONS: Statins reduced the risk of cardiovascular events in men and women, but women on statins may not have reductions in mortality and stroke like their male counterparts. PMID- 17355738 TI - Rivastigmine treatment as an add-on to antipsychotics in patients with schizophrenia and cognitive deficits. AB - OBJECTIVE: Although new atypical antipsychotic agents have been found to improve overall cognitive function in patients with schizophrenia (SZ), some aspects of memory, attention and executive functions still remain impaired. Acetylcholinesterase (AChE) inhibitors, such as rivastigmine, have been shown to improve cognition in other disorders, particularly Alzheimer's disease. Dysfunctions in cholinergic systems, especially in the prefrontal cortex, have been identified in SZ, suggesting that cholinesterase inhibitors may be effective in treating cognitive deficits in this disease. RESEARCH DESIGN AND METHODS: Using a randomized crossover design, we assessed SZ patients with stable symptoms and poor cognitive functioning. Fifty-eight patients with memory deficits, according to subjective complaints or based on clinicians' observations, were assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS). Only 24 of these subjects met the inclusion criteria. Twenty patients took part in the study (four dropped out). All subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for SZ were maintained on their current antipsychotic medication (18 atypicals and two typicals) and were randomly assigned to treatment with rivastigmine. Dosage was a function of tolerability, beginning at 3 mg/day and progressively increasing to 9 mg/day. Subjects were given the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline and 3 and 6 months. RESULTS: The results revealed no significant improvement in any of the cognitive variables investigated following rivastigmine treatment and symptom severity scores remained unchanged over all recorded time periods. CONCLUSION: Rivastigmine treatment did not appear to enhance cognition in SZ patients with important cognitive impairments. This finding needs to be interpreted with care and requires substantiation with larger sample size studies with patients treated with cognitive enhancer for longer periods. PMID- 17355739 TI - A claims database analysis of persistence with alendronate therapy and fracture risk in post-menopausal women with osteoporosis. AB - OBJECTIVE: To explore the relationship between persistence with alendronate therapy and fracture rates in women with postmenopausal osteoporosis. RESEARCH DESIGN AND METHODS: Claims data from a large US health plan database were used to examine persistence with therapy in postmenopausal women followed for 24 months. Persistence was defined as the time (in days) from the date of first fill to the run-out date of the last prescription with no lapses > 30 days after completion of the previous refill. A persistent cohort (length of persistence > or = 182 days) and a nonpersistent cohort (length of persistence < 182 days) were defined. The number of patients with a fracture claim in each cohort was determined. Cox proportional hazards regression (HR) analysis was used to determine significant differences in fracture rates between the two cohorts. RESULTS: 4769 patients were followed for 24 months. Patients in the persistent cohort were significantly more likely to receive a treatment (vs. prevention) dose of alendronate (p = 0.03) and to be older than 65 years (p = 0.04). There was a trend toward more fractures in the non-persistent (4.9%) than in the persistent cohort (3.9%; p = 0.09). When controlled for other significant factors (including age and previous fractures) patients in the persistent cohort were 26% less likely to have a fracture diagnosis claim during the study period than those in the non-persistent cohort (HR = 0.74; 95% CI, 0.549-0.996; p = 0.045). Prescription fill data are an indirect measure of medication-taking behavior. The use of claims data to estimate persistence and identify fracture events prohibits the establishment of causality between these two variables. CONCLUSION: Study results demonstrated that non-persistence with therapy, along with previous fracture and increasing age, was associated with a greater risk of fracture. PMID- 17355740 TI - Intraocular pressure lowering effect of dorzolamide/timolol fixed combination in patients with glaucoma who were unresponsive to prostaglandin analogs/prostamides. AB - OBJECTIVE: To evaluate the intraocular pressure lowering effect of the dorzolamide/timolol fixed combination (DTFC) in non-responder glaucoma patients to prostaglandin analogs/prostamides (prostas). PATIENTS AND METHODS: All glaucoma patients treated with DTFC, between June 2003 and December 2005, who were unresponsive to prostaglandin analogs/prostamides, were identified through a retrospective medical records review. A non-responder was defined as an intraocular pressure (IOP) lowering effect less than 15% compared with baseline measurement. Two 12-hour IOP diurnal curves, measured between 8:00 a.m. and 8:00 p.m. (8:00 a.m., 10:00 a.m., 12:00 noon, 2:00 p.m., 4:00 p.m., 6:00 p.m. and 8:00 p.m.), were obtained retrospectively from the records of 31 patients, the first while on prostaglandin analogs/prostamides (baseline IOP) and the second while receiving DTFC (DTFC IOP). The study outcomes were the change in mean diurnal IOP and the reduction in IOP fluctuation as a result of receiving DTFC in patients unresponsive to prostas. The IOP was evaluated by intragroup comparisons with a two-tailed paired Student's t-test. A chi-square test was adopted for analysis of categorical variables. RESULTS: 31 patients were included in this retrospective study. DTFC significantly reduced IOP in the patients overall, from 25.4 (3.5) to 20.2 (1.0) mmHg, p < 0.0001. The majority of patients were diagnosed with pseudoexfoliative glaucoma (PEX) (58%; 18/31). DTFC reduced the mean IOP fluctuations over 12 hours (highest minus lowest IOP reading within the 12-hours pressure curve) from 8.6 (3.2) to 4.3 (1.4) mmHg, p < 0.0001. The most common adverse events were ocular burning (16%) and taste perversion (13%). There were no serious treatment-related adverse events. CONCLUSION: DTFC significantly reduced the IOP in patients with glaucoma who did not respond to prostaglandin analogs/prostamides. Further research is needed to confirm these results. PMID- 17355741 TI - A meta-analysis of topical prostaglandin analogues intra-ocular pressure lowering in glaucoma therapy. AB - OBJECTIVE: To compare the efficacy of latanoprost, bimatoprost and travoprost for lowering IOP in patients with glaucoma. RESEARCH DESIGN AND METHODS: In order to carry out this meta-analysis, randomized trials (2001-2004) were identified on Medline and EMBASE using the following key words: glaucoma, ocular hypertension (OHT), randomization, trial, latanoprost, bimatoprost and travoprost. The studies had to compare at least two prostaglandin analogues as mono-therapy. Cross-over experimental designs were excluded. The main outcome measure was IOP at final visit. Statistical analyses included random effects, pooled estimates of treatment effects, tests for publication bias, and random-effects models to obtain adjusted treatment effects on final IOP after lowering for baseline IOP, and duration of follow-up. Random effects Poisson regression models were used to estimate the adjusted effects of treatments on response rates (IOP < 18 mmHg). RESULTS: Nine studies were used in the analysis. Patient mean age varied from 56.7 to 68.8 years and baseline IOP ranged from 22.3 to 26.5 mmHg. Three hundred and seventy-eight patients were treated with bimatoprost, 385 with travoprost and 555 with latanoprost. Patients treated with travoprost and bimatoprost had lower IOP levels at the end of follow-up (-0.98 mmHg [95% CI: -2.08; 0.13; p = 0.08] and -1.04 mmHg [95% CI: -2.11;0.04; p = 0.06], respectively) than those treated with latanoprost. The combined effect of newer prostaglandin analogues (bimatoprost/travoprost) was an adjusted decrease of 1.00 mmHg [95% CI: -1.91; 0.10], p = 0.03], or a 17% higher adjusted response rate (Incidence Rate Ratio 1.17, 95% CI, 1.00-1.35, p = 0.04), compared to latanoprost. CONCLUSION: Travoprost and bimatoprost may have greater efficacy in lowering IOP for patients with OHT or glaucoma. PMID- 17355742 TI - Exenatide versus insulin glargine in patients with type 2 diabetes in the UK: a model of long-term clinical and cost outcomes. AB - OBJECTIVES: The aim of this study was to evaluate the long-term clinical and economic outcomes associated with exenatide or insulin glargine, added to oral therapy in individuals with type 2 diabetes inadequately controlled with combination oral agents in the UK setting. METHODS: A published and validated computer simulation model of diabetes was used to project long-term complications, life expectancy, quality-adjusted life expectancy and direct medical costs. Probabilities of diabetes-related complications were derived from published sources. Treatment effects and patient characteristics were extracted from a recent randomised controlled trial comparing exenatide with insulin glargine. Simulations incorporated published quality of life utilities and UK specific costs from 2004. Pharmacy costs for exenatide were based on 20, 40, 60, 80 and 100% of the US value (as no price for the UK was available at the time of analysis). Future costs and clinical benefits were discounted at 3.5% annually. Sensitivity analyses were performed. RESULTS: In the base-case analysis exenatide was associated with improvements in life expectancy of 0.057 years and in quality adjusted life expectancy of 0.442 quality-adjusted life years (QALYs) versus insulin glargine. Long-term projections demonstrated that exenatide was associated with a lower cumulative incidence of most cardiovascular disease (CVD) complications and CVD-related death than insulin glargine. Using the range of cost values, evaluation results showed that exenatide is likely to fall in a range between dominant (cost and life saving) at 20% of the US price and cost effective (with an ICER of 22,420 pounds per QALY gained) at 100% of the US price, versus insulin glargine. CONCLUSIONS: Based on the findings of a recent clinical trial, long-term projections indicated that exenatide is likely to be associated with improvement in life expectancy and quality-adjusted life expectancy compared to insulin glargine. The results from this modelling analysis suggest that that exenatide is likely to represent good value for money by generally accepted standards in the UK setting in individuals with type 2 diabetes inadequately controlled on oral therapy. PMID- 17355743 TI - Metabolic syndrome-related conditions among people with and without gout: prevalence and resource use. AB - OBJECTIVE: A cohort of employees with gout were compared to those without to evaluate the differences in prevalence of disorders associated with metabolic syndrome (both those considered underlying and those associated with end-stage morbidity and mortality) as well as the cost of annual medical services (AMS) required for treatment of these conditions. METHODS: Employees with gout were identified by International Classification of Diseases-9 (ICD-9) code during the calendar years of 2001-2004 and compared to propensity-score matched employees without gout using the Human Capital Management Services Research Reference Database. T-tests were then used to compare prevalence and average AMS of comorbid disorders defined from Agency for Healthcare and Research Quality (AHRQ) diagnostic categories. RESULTS: 'Hyperlipidemia', 'essential hypertension', and 'diabetes mellitus without complications' ranked in the top 10 categories of mean number of AMS for employees with gout using AHRQ specific categories; the values were higher than found for those without gout (all p < 0.0001). 'Essential hypertension', 'hyperlipidemia', 'diabetes mellitus without complications', and 'coronary atherosclerosis' showed an approximate 2:1 prevalence ratio for employees with gout over those without (p < or = 0.05). Main study limitations include the small number of subjects with gout, retrospective study design, and possible miscoding and/or non-coding of individuals with the studied disorders. CONCLUSION: These results support the continued need for patients with gout and their clinicians to be aware of the possibility of the increased risk of associated metabolic syndrome and related comorbidities in these individuals, emphasizing the need for prevention when possible and treatment when necessary. PMID- 17355744 TI - Evaluation of a pharmacokinetic interaction between valsartan and simvastatin in healthy subjects. AB - OBJECTIVE: The potential for a pharmacokinetic drug interaction between valsartan, an antihypertensive drug, and simvastatin, a lipid-lowering agent, was investigated in this study. This was an open-label, multiple-dose, randomized, three-period, cross over study in 18 healthy subjects. Each subject received one 160 mg valsartan tablet or one 40 mg simvastatin tablet or co-administration of valsartan (160 mg) and simvastatin (40 mg) tablets for 7 days, with a 7-day inter dose washout period. The steady-state pharmacokinetics of valsartan, simvastatin beta-hydroxy acid (active metabolite of simvastatin) and simvastatin (pro-drug) were determined on day 7 of each dosing period. RESULTS: The results were interpreted based on the point estimates and the 90% confidence intervals. These results indicated that the area under the curve of plasma concentration from 0 to 24 hours (AUC(0-24)) of valsartan, simvastatin beta-hydroxy acid and simvastatin was increased by 14%, 19%, and 23%, respectively, with the combination treatment. In addition, the maximum concentration (C(max)) of valsartan and simvastatin beta hydroxy acid was increased by 10% and 22%, respectively, and the C(max) of simvastatin was decreased by 26% with the combination treatment. All treatments were safe and well tolerated. CONCLUSIONS: Based on the wide therapeutic dosage ranges of valsartan and simvastatin, and the highly variable pharmacokinetics of three analytes, the observed differences in the exposure and C(max) of valsartan, simvastatin beta-hydroxy acid and simvastatin in the combination treatment are unlikely to be of clinical relevance. PMID- 17355745 TI - Carotid intima-media thickness in low-risk individuals with asymptomatic atherosclerosis: baseline data from the METEOR study. AB - OBJECTIVE: Carotid intima-media thickness (CIMT) is an index for changes in atherosclerosis burden and changes in CIMT may relate to clinical events. We present baseline data from the METEOR study, a randomized, placebo-controlled trial evaluating the efficacy of rosuvastatin 40 mg on changes in CIMT. We set out to compare differences in CIMT between several subgroups of individuals. DESIGN AND METHODS: A total of 984 individuals aged 45-70 years (men) or 55-70 (women) were randomized. Participants were required to have: maximum CIMT > or = 1.2-< 3.5 mm; 2+ risk factors and 10-year coronary heart disease (CHD) risk < 10%, or < 2 CHD risk factors. Demographic characteristics were compared in two groups: USA versus Europe, and individuals with maximum CIMT < 2 mm versus those with CIMT > or = 2 mm. BASELINE DATA: Overall, mean age was 57 years and mean low density lipoprotein cholesterol was 152 mg/dL (3.9 mmol/L). Body mass index (BMI), triglyceride and high-sensitivity C-reactive protein levels were all higher in US individuals, whereas smoking, hypertension and high-density lipoprotein cholesterol levels were higher in Europeans. Mean CIMT levels were the same in both populations, and the percentage of individuals with > or = 2 CHD risk factors was similar. Increased baseline CIMT (> 2 mm) was related to increasing age, male gender, smoking, hypertension and lipid levels. CONCLUSIONS: In this global trial, differences in baseline characteristics between participants from the USA and Europe are apparent. However, a strong association between CIMT and several cardiovascular risk factors was observed across the two continents. PMID- 17355746 TI - Garenoxacin pharmacokinetics in subjects with renal impairment. AB - OBJECTIVE: This open-label, parallel-group study determined the pharmacokinetics of garenoxacin in subjects with severe renal impairment, including subjects maintained on dialysis. RESEARCH DESIGN AND METHODS: Subjects were assigned to one of four groups according to their underlying renal function: creatinine clearance (CL(cr)) > 80 mL/min, CL(cr) < 30 mL/min, hemodialysis (HD), and continuous ambulatory peritoneal dialysis (CAPD). Subjects received a single oral 600-mg dose of garenoxacin. Administration of garenoxacin to subjects receiving hemodialysis was completed in two phases separated by 14 days: 3 h before HD (phase 1) and immediately after HD (phase 2). MAIN OUTCOME MEASURES: Plasma and urine or dialysate samples were analyzed for garenoxacin, and single-dose pharmacokinetic parameters were estimated. Safety was assessed. RESULTS: Twenty five subjects received garenoxacin. Compared with healthy controls, garenoxacin area under the concentration-time curve (AUC) and maximum plasma concentration were increased by 51% and lowered by 20%, respectively, in subjects with severe renal impairment. The terminal half-life was prolonged in subjects with severe renal impairment compared with healthy controls (26.5 +/- 7 h vs 14.4 +/- 3 h, respectively). In subjects receiving HD or CAPD, removal of garenoxacin from systemic circulation was relatively inefficient (HD, 1.5-11.5%; CAPD, 3%), suggesting no need for a supplemental dose of garenoxacin after dialysis. Garenoxacin was well tolerated. CONCLUSIONS: Based on the broad therapeutic index of garenoxacin, the effects of renal impairment on garenoxacin exposure are not considered clinically significant. There was a modest increase in AUC in subjects with severe renal impairment and the magnitude of the changes was not considered clinically relevant. PMID- 17355747 TI - Metallothionein expression in the high-risk carotid atherosclerotic plaque. AB - OBJECTIVE: Metallothioneins (MTs) are antioxidant proteins expressed in response to injury. We evaluated MT immunoreactivity in carotid plaques obtained from asymptomatic and symptomatic patients. We also assessed the relationship between ultrasonic plaque echodensity, histological grading, computed tomography findings and MT expression. METHODS AND RESULTS: In this ongoing prospective study, patients (n = 123, mean age (+/-SD) 68.4 +/- 7.7 years, 97 men) with high-grade carotid stenosis underwent carotid endarterectomy. Specimens were assessed histologically and immunohistochemically. Echolucent plaques (types 1+2) were more common in symptomatic patients (p < 0.0001) and had more advanced histological lesions (p < 0.0001). Echolucent plaques expressed MTs (in macrophages, fibroblasts and T-lymphocytes) significantly more than echogenic plaques (types 3+4) (all p < 0.0001). MT expression was mainly related to carotid plaque echolucency rather than the presence of symptoms. MT expression was significantly more common in advanced histological lesions. Plaques from asymptomatic or symptomatic patients with abnormal computed tomography findings also showed increased MT expression. There was a time-dependent fall in MT expression after cerebrovascular events (p < or = 0.011). CONCLUSIONS: MT overexpression may be triggered in unstable plaques as a local protective factor. There is a need to identify both causative and protective predictors of the 'vulnerable plaque' in the 'vulnerable patient'. Further studies are needed to resolve these issues. PMID- 17355760 TI - Cause of death. PMID- 17355761 TI - A new questionnaire for quick assessment of food tolerance after bariatric surgery. AB - BACKGROUND: Bariatric surgery is often associated with reduced food tolerance and sometimes frequent vomiting, which influence quality of life, but are not included in the overall evaluation of these procedures, notably the BAROS. Our aim was to develop a simple questionnaire to evaluate food tolerance during follow-up visits. METHODS: A one-page questionnaire including questions about overall satisfaction regarding quality of alimentation, timing of eating over the day, tolerance to several types of food, and frequency of vomiting/regurgitation was developed. A composite score was derived from this questionnaire, giving a score of 1 to 27. Validation was performed with a group of non-obese adults and a group of morbidly obese non-operated patients. Patients were administered the questionnaire at follow-up visits since January 1999. Data were collected prospectively. RESULTS: It takes 1-2 minutes to fill out the questionnaire. Food tolerance is worse in the morbidly obese population compared with non-obese adults (24.2 vs 25.2, P=0.004). Following Roux-en-Y gastric bypass, food tolerance is reduced after 3 months (21.2), but becomes comparable to that of the normal population and remains so at 1 year postoperatively. Following gastric banding, food tolerance is already significantly reduced after 3 months (22.3), and worsens continuously over time (19.03 after 7 years). In the gastric banding population, the decision to adjust the band is based at least partially on food tolerance, and the questionnaire proved helpful in that respect. CONCLUSIONS: Our new questionnaire proved very easy to use, and helpful in day-to-day practice, especially after gastric banding. It was also helpful in comparing food tolerance over time after surgery, and in comparing food tolerance between procedures. Evaluation of food tolerance should be part of the overall evaluation of the results after bariatric surgery. PMID- 17355762 TI - Causes of 30-day bariatric surgery mortality: with emphasis on bypass obstruction. AB - BACKGROUND: This is a study of the causes of 30-day postoperative death following surgical treatment for obesity and a search for ways to decrease an already low mortality rate. METHODS: Data were contributed from 1986-2004 to the International Bariatric Surgery Registry by 85 sites, representing 137 surgeons. A spread-sheet was prepared with rows for causes and columns for patients. The 251 causes contributing to 93 deaths were then marked in cells wherever a patient was noted to have one of the causes. Rows and columns were then moved into positions that provided patterns of best fit. RESULTS: 11 patterns were found. 10 had well known initiating causes of death. Overall operative 30-day mortality was 0.24% (93 / 38,501). The most common cause of death was pulmonary embolism (32%, 30/93). 14 deaths were caused by leaks (15%, 14/93), and were equally prevalent after simple (15%, 2/14) or complex (15%, 12/79) operations. Small bowel obstruction caused 8 deaths, exclusively after complex operations. 5 of these involved the bypassed biliopancreatic limb and were defined as "bypass obstruction". CONCLUSIONS: A spread-sheet study of cause of 30-day postoperative death revealed a rapidly lethal initiating complication of Roux-en-Y gastric bypass obstruction that requires the earliest possible recognition and treatment. Bypass obstruction needs a name and code to facilitate recognition, study, prevention and early treatment. Spread-sheet pattern analysis of all available data helped identify the initiating cause of death for individual patients when multiple data elements were present. PMID- 17355763 TI - Omental wrap: a simple technique for reinforcement of the gastrojejunostomy during Roux-en-Y gastric bypass. AB - BACKGROUND: Anastomotic leak is one of the most dreaded complications following Roux-en-Y gastric bypass (RYGBP). A simple technique for reinforcement of the gastrojejunal anastomosis using an omental wrap during laparoscopic RYGBP is described. We recommend this technique particularly in those patients at high risk for gastrojejunal leak. METHODS: A 20 ml vertically-oriented gastric pouch, based on the lesser curvature of the stomach, is created using linear cutter staplers (endo-GIA). The gastrojejunal anastomosis is reinforced with an omental wrap (omental flap). The jejunojejunostomy is created 100-150 cm from the gastrojejunostomy, depending on the BMI. RESULTS: 124 laparoscopic RYGBPs were performed by the same surgeon. The omental wrap was successfully performed in all patients but two. There were no mortalities, leakages, or stenoses noted during follow-up. CONCLUSION: During RYGBP, reinforcement of the gastrojejunostomy with an omental wrap is a simple, feasible, and protective adjunctive maneuver that can minimize the risk of gastrojejunal leak. PMID- 17355764 TI - Skills acquisition for laparoscopic gastric bypass in the training laboratory: an innovative approach. AB - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is a technically demanding procedure, with a long learning curve. The aim of this study was three fold: to develop a task-based approach to training in LRYGBP, define a tool for objective technical skills assessments, and objectively determine the efficacy of this approach. METHODS: Videos of expert and novice surgeons performing LRYGBP on patients and anesthetised porcine models were analyzed to define an appropriate task for skills assessment. Subsequently, a jejuno-jejunostomy model was developed using cadaveric porcine small bowel, placed into a video-box trainer. 27 surgeons of varying experience levels in advanced laparoscopic procedures performed the task. Assessments of technical skill were by hand motion analysis and video-based scoring. A further 16 surgeons inexperienced in LRYGBP attended a task-based hands-on training course and performed the jejuno-jejunostomy task at start and end of the course. RESULTS: The jejuno-jejunostomy model differentiated between surgeons of varying experience levels for time taken (P<0.001), economy of movement (P=0.001) and video scores (P<0.001). Surgeons attending the training course made significant improvements in time taken (P=0.002) and economy of movement (P=0.006), although not for generic video scores (P=0.243) by the end of course. CONCLUSIONS: The structured, task-based approach for commencement of training in LRYGBP leads to objective improvements in the technical skills of inexperienced surgeons at the end of a short course. The next stage of the curriculum should be to achieve proficiency in the complete procedure on an anesthetised porcine model, prior to preceptorship on human cases. PMID- 17355765 TI - Endoscopic and histologic findings of the foregut in 426 patients with morbid obesity. AB - BACKGROUND: Roux-en-Y gastric bypass is the most frequent bariatric operation. In this operation, the distal bypassed stomach is left in situ. We studied pre operative clinical, endoscopic and histologic findings in a consecutive group of morbidly obese patients prior to bariatric surgery. METHODS: A prospective study was conducted from August 1999 until May 2004, which consisted of 426 patients with morbid obesity. There were 94 men and 332 women, with mean age 39.5 years. In all patients prior to surgery, upper endoscopy was performed and biopsy samples were taken distal to squamo-columnar junction (cardiac biopsies), and in 232 of them also in at the antrum. RESULTS: Pathological findings at the esophagus were seen in 55% of the patients, mainly related to reflux esophagitis. Barrett's esophagus was seen in 5.8%. In the stomach, pathological findings were seen in 32% of the patients. Active peptic ulcer was demonstrated in 2.6% of the cases. At the duodenum, pathologic findings were detected in 13.4% of the patients, showing an ulcer in 2.6%. At the stomach, chronic inactive gastritis and atrophic gastritis with intestinal metaplasia were found in 8.6% and 6.5% respectively. Antral adenoma with low-grade dysplasia was found in 1 patient, and 1 carcinoid tumor. H. pylori was present in 53% of the patients, mainly in the antrum. CONCLUSION: In candidates for bariatric surgery, upper endoscopy with biopsy samples and determination of H. pylori should be routinely performed. If present, H. pylori should be eradicated. After surgery, if Barrett's esophagus was present, endoscopic surveillance is recommended. PMID- 17355766 TI - Laparoscopic re-operations for band removal after open banded gastric bypass. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) has been demonstrated to be an effective treatment for weight loss in the morbidly obese. Numerous variations of the RYGBP have been performed, including placing a ring proximal to the gastric outlet. This ring in RYGBP is intended to decrease pouch dilation and limit weight regain. We reviewed our experience in laparoscopic re-operation after open banded RYGBP. METHODS: All charts of patients who underwent laparoscopic revisional bariatric surgery were reviewed. Patients who had laparoscopic removal of the band following the open banded RYGBP were reviewed in this study. RESULTS: There were 4 patients who had laparoscopic removal of the band. The indication in all patients was dysphagia and emesis. The ring removed was a silicone band (1) and a large braided non-absorbable suture (3). After the laparoscopic reoperation, there was immediate relief. There has been an average of 5.8 kg weight regain at average follow-up of 30 months. CONCLUSIONS: This complication after open banded RYGBP may require operative intervention. Laparoscopic removal of a band is feasible and safe. PMID- 17355767 TI - A nationwide survey on bariatric surgery in France: two years prospective follow up. AB - BACKGROUND: Most studies on bariatric surgery outcomes have been performed in clinical trials (eg. the SOS) or reflect the clinical experience and practice of specific and experienced centers. Little is known about the current practice at a nationwide level. METHODS: This is a systematic nationwide study on the 2-year outcome of all consecutive 1,236 bariatric operations performed in France. Data on mortality, weight loss, complications, and patient satisfaction were collected independently from the medical and surgical team involved in the patients' care. RESULTS: 87.3% of the patients underwent an adjustable gastric banding (ABG), 8.6% a vertical banded gastroplasty (VBG), 3.8% a Roux-en-Y gastric bypass (RYGBP) and 0.3% a biliopancreatic diversion (BPD). Loss of follow-up was 12% at year 1 and 18% at year 2. The rate of laparoscopic procedures was 98% for ABG and 73% for RYGBP. Mortality rate was 0.16% in the operative period and 0.27% during follow-up. Excess weight loss ranged from 43% (AGB) to 66% (RYGBP). Co morbidities improved in more than 70% of patients. CONCLUSION: Outcomes of bariatric surgery in routine practice (mortality, weight loss, course of co morbidities, and quality of life) are similar to the results published in clinical trials. PMID- 17355768 TI - Diagnostic value of ultrasonographic examination for nonalcoholic steatohepatitis in morbidly obese patients undergoing laparoscopic bariatric surgery. AB - BACKGROUND: There are few data relating to the role of fatty score (FS) and modified fatty score (MFS) in ultrasonographic (US) examination on the diagnosis of nonalcoholic steatohepatitis (NASH) in patients undergoing bariatric surgery. METHODS: We investigated consecutive patients undergoing laparoscopic bariatric surgery with biopsy-proven nonalcoholic fatty liver disease. Patients with other liver diseases and significant alcohol consumption were excluded. Clinico demographic and anthropometric data were collected before surgery. Each biopsy specimen was assessed by the same pathologist. Liver US examinations were performed by an independent and experienced sonographer before surgery. FS and MFS, determined by the US scoring system based on degrees of parenchymal echogenicity, far gain attenuation, gallbladder wall blurring, portal vein wall blurring and hepatic vein blurring, were used to assess the severity of fatty liver. US findings were correlated with histologic results. RESULTS: Totally 101 patients were enrolled. The mean BMI of the patients was 44.6 +/- 5.4 kg/m(2). 29 patients (29%) were categorized with simple steatosis and 72 (71%) with NASH. FS and MFS were significantly correlated with the histological steatosis, fibrosis and the presence of NASH (P<0.001). A receiver operating characteristic curve identified the MFS of 2 as the best cut-off point for the prediction of NASH, yielding measures of sensitivity, specificity, positive predictive value, and accuracy for 72%, 86%, 93% and 76%, respectively. The positive likelihood ratio of 5.24 for MFS approximately doubled the post-test probability of NASH from 30% to 70%. CONCLUSION: FS and MFS on US examination exhibit acceptable sensitivity and high specificity for the detection of the presence of NASH in morbidly obese patients and may aid in the selection of patients for closer follow-up or liver biopsy. PMID- 17355769 TI - Sleeve gastrectomy: a restrictive procedure? AB - BACKGROUND: Diet and surgically-induced weight loss have been shown to lead to alterations in motor and sensory function of the stomach. We investigated the clinical outcome and gastric emptying of solid foods in morbidly obese (MO) patients following sleeve gastrectomy (SG). METHODS: We studied 23 MO patients [(7 males, 16 females), mean age 38.9 +/- 11.0 years (range 20-64 years), mean weight 135.1 +/- 19.0 kg (range 97-167 kg), mean BMI 47.2 +/- 4.8 kg/m(2) (range 39.6-56.0 kg/m(2))] who each underwent a sleeve gastrectomy (SG) for weight reduction. At the monthly follow-up visits, variations in weight and BMI changes, postoperative meal size and frequency, and presence of gastrointestinal symptoms were recorded. 11 patients underwent scintigraphic measurement of the gastric emptying of a solid meal pre- and 6 months postoperatively. RESULTS: A significant reduction in patients' weight was evidenced at 6 and 12 months postoperatively [98.6 +/- 11.8 kg and 87.0 +/- 10.7 kg respectively (P=0.001)]. BMI decreased to 35.2 +/- 4.3 kg/m(2) at 6 months and to 31.1 +/- 4.5 kg/m(2) at 12 months, respectively (P=0.001). Although meal size was drastically reduced, meal frequency increased postoperatively in 12 patients (52.2%). Only 5 patients (21.8 %) reported occasional vomiting after meals following SG. The gastric emptying half-time (T1/2) accelerated (47.6 +/- 23.2 vs 94.3 +/- 15.4, P<0.01) and the T-lag phase duration decreased (9.5 +/- 2 min vs 19.2 +/- 2 min, P<0.05) post-operatively. The percentage of the meal emptied from the stomach 90 min after consumption increased significantly after SG (75.4 +/- 14.9% vs 49.2 +/- 8.7%, P<0.01). CONCLUSIONS: This study indicates that following SG, the stomach empties its contents rapidly into the small intestine and symptoms of vomiting after eating (characteristic of restrictive procedures) are either absent or very mild. Therefore, the term 'restrictive' is possibly ill-advised for this new bariatric operation. It remains for other mechanisms of energy intake reduction, such as intestinal distension and satiety signals through gut hormones to be investigated, to comprehensively explain precisely how this 'food limiting' procedure results in weight loss. PMID- 17355770 TI - Perforator-sparing abdominoplasty technique in the presence of bilateral subcostal scars after gastric bypass. AB - BACKGROUND: The number of patients after gastric bypass being referred to plastic surgery units for secondary plastic surgery procedures is increasing. The characteristic abdominal deformity includes a draping apron of panniculus, occasionally associated with previous transverse surgical scars in the upper abdomen. Often a limited abdominoplasty of the low transverse type with limited undermining only up to the level of the umbilicus is performed in order not to compromise blood supply in the zone between the old transverse and the new transverse scar. METHOD: We propose a new, modified and safe surgical technique to perform a complete abdominoplasty with wide undermining up to the xiphoid process in patients with preexisting transverse subcostal scars after gastric bypass surgery, by selectively dissecting and preserving one to three periumbilical abdominal wall perforator vessels to secure flap blood supply. Vessel tunnelling through the rectus sheath and muscle and ligation of the cephalad branch of the perforator provide sufficient flap mobility without perforator tension or traction. Flap undermining is performed around these perforator vessels. To match dissected flap perforators with blood-flow, we performed post-operative color-flow duplex scanning. RESULTS: We treated two patients according to this new technique. In both cases the postoperative course was uneventful and a good aesthetic result was achieved. CONCLUSION: We conclude from our experience that with this perforator-sparing abdominoplasty technique, safe and complete abdominoplasty can be performed with no additional risk of complications and that a good cosmetic result can be achieved in patients after open gastric bypass surgery. PMID- 17355771 TI - Attitudes of morbidly obese patients to weight loss and body image following bariatric surgery and body contouring. AB - BACKGROUND: The authors evaluated body image attitudes in post-obese persons following bariatric surgery who require cosmetic and body contouring operations. METHODS: We studied 20 morbidly obese women prior to biliopancreatic diversion (BPD) (OB group), 20 post-obese women at >2 years following BPD (POST group), 10 post-obese women following BPD who required cosmetic procedures (POST-A group), 10 post-obese women after BPD and subsequent cosmetic surgery (POST-B group), and 20 healthy lean controls. Attitudes to weight and shape were evaluated by means of the Body Uneasiness Test (BUT). RESULTS: In comparison with the obese patients in the POST group, lower BUT scores were observed, while in the POST-A group the values were very similar to those observed in the non-operated obese individuals. In the individuals having received cosmetic surgery, the BUT findings were similar to those recorded in the POST group patients, the values approaching data found in the controls. CONCLUSION: Despite a fully satisfactory weight loss and maintenance, the post-BPD individuals requiring aesthetic surgery showed some disparagement of body image; in these subjects, cosmetic and body contouring procedures may actually improve body weight and shape attitudes towards normality. PMID- 17355772 TI - Do patients' unrealistic weight goals have prognostic significance for bariatric surgery? AB - BACKGROUND: Research has shown that obese individuals report goal weight losses in excess of those achievable with standard treatments for obesity. Little is known about the goal weights of bariatric surgery patients, or the prognostic significance of unrealistic goals on surgical outcomes, including weight losses and changes in associated behavioral and psychological domains. METHODS: A consecutive series of 139 gastric bypass (GBP) surgery candidates reported weight loss goals prior to GBP surgery and at 6 and 12 months after surgery. Dream, Happy, Acceptable, and Disappointed weights following treatment were reported. RESULTS: Consistent with previous research, goal weights at baseline were lower than those attainable even with surgery. Repeated measures analyses, controlling for baseline BMI, revealed no changes in any of the goal weights from baseline to 6 and 12 months following surgery. After controlling for baseline BMI, weight loss expectations at baseline did not predict weight loss at either follow-up point. Unrealistic weight goals were also largely unrelated to psychological functioning prior to surgery, and were unrelated to the magnitude of the improvements in eating-related behaviors and psychological functioning after surgery. Interestingly, mean goal weights parallel current weight classifications: i.e., dream BMI corresponds with the cutoff for normal (BMI < or =25), happy BMI (=27) with the lower bound for "overweight", and acceptable BMI (=30) with the lower bound for obesity. CONCLUSIONS: Among GBP surgery patients, goal weights are remarkably consistent over time, and unrealistic weight loss goals do not appear to have negative prognostic significance on surgical outcomes. PMID- 17355773 TI - Obesity surgery in the Philippines: experience in a private tertiary care hospital for years 2002 to 2004. AB - BACKGROUND: Information on experience in bariatric surgery in the Asia-Pacific region is minimal: hence the need for more reports from this area. METHODS: The procedures of bariatric surgery and outcome as part of a weight management program in a tertiary care private hospital in the Philippines is reported from years 2002 to 2004. 50 patients were included, of which 60% underwent laparoscopic adjustable gastric banding (LAGB) and 40% Roux-en-Y gastric bypass (RYGBP). RESULTS: There were more females than males (64% vs 36%) with the mean age 38 +/- 13.1 years. Initial mean BMI was 46.2 kg/m(2), which decreased to 27.0 kg/m(2) in 1 year. Initial mean weight was 126.7 +/- 25.4 kg, of which the 1 year weight loss was 32.3 kg for the morbidly obese and 58.0 kg for the super obese. %EWL at 1 year was 30.2%. There was greater weight loss with RYGBP compared to LAGB at 1 year (43.5 kg vs 30.2 kg). There was no mortality, and early complications were: wound infection (2/50 or 4%), and 1/50 or 2% each for pneumonia, dehydration, gastritis, and leakage. Late complications were: band slippage (2/20 or 10%), stomal stenosis (1/20 or 5%), and ventral hernia (1/5 or 20%). CONCLUSION: Bariatric surgery is safe with a low complication rate and the outcome was similar to the reported data from Asia and the western world. PMID- 17355774 TI - Six months of balloon treatment does not predict the success of gastric banding. AB - BACKGROUND: We studied whether weight loss by intragastric balloon would predict the outcome of subsequent gastric banding with regard to weight loss and BMI reduction. METHODS: A prospective cohort of patients with a body mass index (BMI)>40 kg/m(2) received an intragastric balloon for 6 months followed by laparoscopic adjustable gastric banding (LAGB). Successful balloon-induced weight loss was defined as > or =10% weight loss after 6 months. Successful surgical weight loss was defined as an additional 15% weight loss in the following 12 months. Patients were divided in group A, losing > or =10% of their initial weight with 6 months' balloon treatment, and group B, losing <10% of their initial weight. RESULTS: In 40 patients (32 female, 8 male; age 36.6 yr, range 26 54), the mean BMI decreased from 46.5 to 40.5 kg/m(2) (P<0.001) after 6 months of balloon treatment and to 35.2 kg/m(2) (P<0.001) 12 months after LAGB. Group A (25 patients) and group B (15 patients) had a significant difference in BMI decrease, 12.4 vs 9.0 kg/m(2) (P<0.05), after the total study duration of 18 months. However, there was no difference in BMI reduction (4.7 kg/m(2) vs 5.8 kg/m(2)) in the 12 months after LAGB. 6 patients in group A lost > or =10% of their starting weight during 6 months balloon treatment as well as > or =15% 12 months following LAGB. 6 patients in group B lost <10% of their starting weight after 6 months of BIB, but also lost > or =15% 12 months following LAGB. CONCLUSION: Intragastric balloon did not predict the success of subsequent LAGB. PMID- 17355775 TI - Obesity and obstructive sleep apnea-hypopnea syndrome: the impact of bariatric surgery. AB - Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by successive episodes of cessation or decrease in respiratory airflow, in which obesity is an important risk factor. The prevalence of the disease in morbidly obese patients is approximately 70%. Treatment is based on the use of continuous positive airway pressure (CPAP) and weight loss in obese patients. Weight loss by dieting often produces unsatisfactory results, and the use of CPAP does not show good adherence because of being long-term and uncomfortable. Bariatric surgery has emerged as the treatment for morbid obesity and various associated co-morbidities. This article reviews the principal studies that evaluate the modifications in obstructive sleep apnea after bariatric surgery, showing that surgery is an effective treatment for the management of OSAHS in morbidly obese patients. PMID- 17355776 TI - Laparoscopically implanted gastric pacemaker after kidney-pancreas transplantation: treatment of morbid obesity and diabetic gastroparesis. AB - Combined kidney-pancreas transplantation is the treatment of choice for end-stage diabetic nephropathy. Weight gain post-transplant increases the risk for post transplant complications and death due to cardiovascular events. Gastric pacemakers have been used for therapy of diabetic gastropathy and for the treatment of moderate morbid obesity. We report a patient who experienced significant weight gain following successful kidney-pancreas transplantation and was thereafter successfully treated for diabetic gastroparesis and morbid obesity by use of a laparoscopically implanted gastric pacemaker. PMID- 17355777 TI - Mini-gastric bypass in a patient homozygous for Factor V Leiden. AB - A 42-year-old morbidly obese female, homozygous for Factor V Leiden, underwent mini-gastric bypass without complications. The recommendations for prophylaxis in this high-risk population are unclear and most likely involve a combination of pharmacologic and non-pharmacologic measures. PMID- 17355778 TI - Gastro-gastric fistula between pouch and fundus following gastric banding and bypass. AB - A complication observed with revisional surgery involving a fistula between the former pouch after gastric banding and the fundus is described. A 59-year-old man with BMI 41 kg/m(2) presented for Roux-en-Y gastric bypass (RYGBP). He had previously undergone an open gastric banding operation, with the band removed for obstruction 1 year later. He presented to our hospital with a third incisional hernia which was so large that he suffered from abdominal angina following meals. A RYGBP and a hernia repair with mesh were performed. The postoperative contrast x-ray study disclosed a fistula between the pouch and fundus. A procedure to close the fistula became necessary. The reason for the fistula may have been an erosion at the former connection between the pouch and the fundus after gastric banding, although a preoperative gastroscopy had not revealed this fistula. PMID- 17355779 TI - Greco-Roman and Byzantine views on obesity. AB - This paper focuses on the Greco-Roman views on obesity with certain extensions to the Byzantine era. The writers reported hereby are Aulus Cornelius Celsus (circa 25 BC), Dioscorides Pedanius (40-90 AD), Soranus of Ephesus (98-138 AD) whose writings on the subject survived through Caelius Aurelianus (5th c. AD), Claudius Aelianus (3rd C. AD), Oribasius (324-400 AD), Aetius of Amida (circa 450 AD), Alexander Trallianus (6th c. AD), Paulus Aegineta (7th c. AD), and Theophilus Protospatharius (9th C. AD). All of the authors treat the subject of etiology, clinical manifestations and treatment, while the Hippocratic and Galenic views seem to be taken into consideration. The most important observation made on the basis of the studied texts is the emersion of the notion of the "Mediterranean diet" that was advised as an extremely successful conservative way to treat obesity. The Greco-Roman and Byzantine writers continue the long tradition of treating obesity and set the foundations for modern methods of treatment. PMID- 17355780 TI - End-to-side duodeno-jejunostomy with half-and-half biliopancreatic limb for the treatment of type 2 diabetes: a proposal for a simpler technique. PMID- 17355781 TI - [Development of the general module of the system of quality of life instruments for cancer patients: reliability and validity analysis]. AB - BACKGROUND & OBJECTIVE: The general module of the system of quality of life instruments for cancer patients (QLICP-GM) has been developed by us, but its psychologic properties need to be evaluated. This study was to evaluate the reliability and validity of QLICP-GM. METHODS: The QOL data of 600 patients with lung cancer, breast cancer, colorectal cancer, gastric cancer, and head and neck cancer were analyzed by paired t-tests, correlation analysis, equivalence tests, and structural equation models to evaluate QLICP-GM. RESULTS: The test-retest reliability for all domains and the overall scale was above 0.85. Internal consistency alpha values for all domains except social function domain were above 0.70. The alpha value and split-half reliability of the overall scale were 0.88 and 0.93, respectively. Correlation analyses and structural equation models displayed good construction validity of the scale. It also showed good criterion related validity when FACT-G was used as the criterion. CONCLUSION: QLICP-GM can be used to measure QOL for cancer patients with good reliability and validity. PMID- 17355782 TI - [Effects of vesicular stomatitis virus matrix protein on proliferation and apoptosis of mouse LL/2c cells]. AB - BACKGROUND & OBJECTIVE: Vesicular stomatitis virus (VSV), an oncolytic virus, is an attractive candidate for tumor therapy. Although previous studies showed obvious antitumor effects of VSV on human A549 and mouse LL/2c tumor models, the clinical application of a live virus is confronted with the problem of bio safety. The matrix (M) protein of VSV is related to the antitumor effect of VSV. This study was to investigate the effects of VSV-M protein on the proliferation and apoptosis of mouse LL/2c tumor cells. METHODS: A eukaryotic expression plasmid pcDNA3.1-M encoding VSV-M protein was constructed by molecular cloning technique, and analyzed by enzyme digestion, polymerase chain reaction (PCR), and DNA sequencing, then transfected into LL/2c cells. The expression of VSV-M protein in LL/2c cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The effect of VSV-M protein on proliferation of LL/2c cells was assessed by MTT assay; its effect on cell apoptosis was assessed by DNA ladder and Hoechst 33528 staining. RESULTS: A plasmid pcDNA3.1-M encoding VSV-M protein was constructed successfully and identified. After transfection, the expression of VSV-M protein was detected in LL/2c cells, morphologic changes of LL/2c cells was observed under microscope, inhibition rate of cell survival was 41.3% (P<0.05), DNA ladder was detected, apoptotic nuclei was observed. CONCLUSION: VSV-M transfection could inhibit proliferation and induce apoptosis of LL/2c cells. PMID- 17355783 TI - [Molecular characteristics of T-cell receptor of clonal expansion of T lymphocytes in leukemia patients after haploidentical bone marrow transplantation]. AB - BACKGROUND & OBJECTIVE: Previous clinical and experimental results indicate that T-cell immune reconstitution is slow after hematopoietic stem cell transplantation. Immune reconstitution after haploidentical bone marrow transplantation (BMT) is closely related to clinical events. This study was to analyze the repertoire of T-cell receptor beta chain variable region (TCRBV) and the molecular characteristics of T-cell clones during immune reconstitution in leukemia patients after haploidentical BMT. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify 24 genes of TCRBV subfamily from peripheral blood lymphocytes of 9 leukemia patients after haploidentical BMT, and 5 healthy donors as control. The PCR products were analyzed by GeneScan to evaluate the clonality of BV subfamily, characteristics of complementarity determining region 3 (CDR3), and usage rate of BV subfamily. Graft-versus-host disease (GVHD)-related monoclonal bands were sequenced. RESULTS: During 10-19 months after haploidentical BMT, the usage of TCRBV subfamily was still restricted. Deletion of some BV subfamily members was detected, while others expanded in monoclonal or oligoclonal. For 4 patients with stable disease, the expression of 9-14 BV subfamily members was detected, and more than 50% of them were polyclones. For other 5 patients with GVHD or cytomegalovirus (CMV)-pp65 infection, the usage of TCRBV decreased obviously(P<0.05), the expression of CDR3 were monoclonal or oligoclonal, only 30% were polyclonal. No common monoclonal BV subfamily members were detected. After treatment, the usage of BV subfamily and CDR3 polymorphism were increased in 2 patients. By analyzing the sequences associated with GVHD, none of the clones appeared to share any similarity in amino acid motif. CONCLUSIONS: In 10 19 months after haploidentical BMT, the usage of TCRBV subfamily members is still restricted. In stable condition, there are 9-14 BV subfamily members expressed and dominated by polyclones. In active condition, the expression of BV subfamily members is decreased and dominated by monoclones or oligoclones. A group of CDR3 molecules related to GVHD show no common amino acid motif to be shared. PMID- 17355784 TI - [Activation of formylpeptide receptor in human malignant glioma cells and its effects on cell proliferation and production of angiogenic factors]. AB - BACKGROUND & OBJECTIVE: Chemoattractant receptors participate in essential pathophysiologic processes, including inflammation, wound healing, human immunodeficiency virus infection, and most interestingly in the progression of malignant tumor. This study was to explore the functional expression of formylpeptide receptor (FPR) in human glioblastoma cell line U87. METHODS: The expression of FPR in U87 and FPR small interfering RNA (siRNA)-transfected U87 cells (FPR-siRNA-U87 cells) was detected with indirect immunofluorescent staining by confocal laser scanning microscopy. FPR was activated by its ligand formy-Met Leu-Phe (fMLF). Cell proliferation was assessed by MTT assay. The production of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) was measured by ELISA, and IL-8 mRNA was assessed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: FPR was expressed on U87 cells, but not on FPR-siRNA U87 cells. After activation of FPR by fMLF, the proliferation of U87 cells was enhanced markedly (P<0.05), but that of FPR-siRNA-U87 cells had no obvious change (P>0.05). fMLF (100 nmol/L) elicited a time-dependent increase in the secretion of IL-8 and VEGF. When stimulated with 100 nmol/L fMLF for 36 h, the protein levels of VEGF and IL-8 were significantly higher in stimulated U87 cells than in control cells [(3.13+/-0.23) ng/ml vs. (2.55+/-0.25) ng/ml, P<0.05u (7.54+/-0.53) ng/ml vs. (4.02+/-0.09) ng/ml, P<0.05], but those in FPR-siRNA-U87 cells had no obvious change; the mRNA level of IL-8 was significantly increased in U87 cells, but not changed in FPR-siRNA-U87 cells. CONCLUSION: Activating FPR can promote the proliferation of U87 cells and enhance the production of angiogenic factors. PMID- 17355785 TI - [Expression of PTEN gene in human glioma cell lines U251 and SHG-44 and its effect on cell proliferation]. AB - BACKGROUND & OBJECTIVE: Mutation or deletion of PTEN gene is related to a variety of tumors. PTEN gene abnormality is closely related to the tumorigenesis of glioma. This study aimed to investigate the expression of PTEN gene in human glioma cell lines U251 and SHG-44, and explore its effect on cell proliferation. METHODS: The expression of PTEN gene in U251 and SHG-44 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). The recombinant eukaryotic expression vector containing wild-type PTEN gene was transfected into U251 and SHG-44 cells by cation polymex. The stably transfected cells were selected by G418 and amplified. Cell morphology was observed under microscope. The effect of PTEN gene on cell proliferation was assessed. The expression of PTEN protein and glial fibrillary acidic protein (GFAP) were detected by Western blot and immunohistochemistry. RESULTS: Point mutation and deletion of PTEN mRNA were observed respectively in U251 and SHG-44 cells. The proliferation rates of U251 and SHG-44 cells were inhibited by 39.1% and 27.8% of control at 7 days after transfection. The expression of PTEN and GFAP were both increased. The stably transfected U251 cells differentiated toward astrocytes, but SHG-44 cells had no obvious morphologic changes. CONCLUSION: Restoring expression of wild-type PTEN could induce differentiation of glioma cells differently. PMID- 17355786 TI - [Effect of Ku80 expression inhibition by RNA interference on proliferation of cervical carcinoma cell line HeLa]. AB - BACKGROUND & OBJECTIVE: Ku80 is a key protein plays a role in repairing DNA double strand break (DSB) after irradiation. There are a few studies about other roles of Ku80 except DSB repair. This study was to inhibit Ku80 expression in cervical carcinoma cell line HeLa with small interfering RNA (siRNA), and explore its effect on cell proliferation. METHODS: Plasmids pKu80-siRNA and pNeg-siRNA (negative control) were constructed and transfected into HeLa cells. The expression of Ku80 in HeLa cells was detected by Western blot. The proliferation of HeLa cells in vitro and in vivo was determined by clone formation assay, MTT assay, and subcutaneous tumor formation in nude mice. RESULTS: Two cell clones were screened from pKu80-siRNA-and pNeg-siRNA-transfected HeLa cells. Ku80 expression in HeLa cells was suppressed markedly after transfection of pKu80 siRNA; this clone was named Hela/Ku80-siRNA. The clone formation efficiency was significantly lower in HeLa/Ku80-siRNA cells than in control cells (0.46+/-0.05 vs. 0.62+/-0.02, t=5.11, P<0.01). The proliferation rate was significantly lower in HeLa/Ku80-siRNA cells than in control cells at 48 h and 72 h after transfection (P<0.05). At the 25th day after subcutaneous transplantation in nude mice, the tumor volume was significantly smaller in HeLa/Ku80-siRNA group than in control group [(18.92+/-3.60) mm(3) vs. (194.88+/-30.61) mm(3), t=12.69, P<0.01]. CONCLUSIONS: We successfully established a cell model that Ku80 expression is suppressed almost completely by siRNA. Ku80 inhibition inhibits the proliferation of HeLa cells in vivo and in vitro. PMID- 17355787 TI - [Correlation of autophagy gene Beclin1 to tumorigenesis and development of epithelial ovarian cancer]. AB - BACKGROUND & OBJECTIVE: Some studies have showed that autophagy suppression may result in malignant transformation, and the inactivation of autophagy gene Beclin1 induces malignancy. This study was to investigate the role of Beclin1 in the tumorigenesis and development of epithelial ovarian carcinoma, and to explore the effect of Beclin1 overexpression on the growth of ovarian carcinoma cell line SKOV3 in vitro. METHODS: The expression of Beclin1 in 25 specimens of normal ovarian tissue, 25 specimens of benign ovarian neoplasia, 19 specimens of borderline ovarian tissue, and 69 specimens of epithelial ovarian carcinoma was detected by immunohistochemistry. Eukaryotic expression vector pcDNA3.1/Beclin1 was constructed and transfected into SKOV3 cellsu plasmid pcDNA3.1 was used as control. The effect of Beclin1 overexpression on the proliferation of SKOV3 cells was evaluated by MTT assay. Cell apoptosis was measured by flow cytometry (FCM). RESULTS: The expression of Beclin1 was high in normal and benign ovarian neoplasia tissues, and there was no significant difference between the 2 groups (P>0.05). Reduced Beclin1 expression was observed in borderline lesions, and the lowest level was detected in ovarian carcinoma tissues (P<0.05). The inhibition rate was significantly higher in pcDNA3.1/Beclin1-SKOV3 cells than in pcDNA3.1 SKOV3 cells [(68.75+/-5.10)% vs. (10.91+/-4.20)%, P<0.05]. At 72 h after transfection, the apoptosis rate was significantly higher in pcDNA3.1/Beclin1 SKOV3 cells than in pcDNA3.1-SKOV3 cells and SKOV3 cells [(19.07+/-0.65)% vs. (4.30+/-0.50)% and (3.87+/-0.84)%, P<0.05]. CONCLUSIONS: Beclin1 expression is down-regulated in epithelial ovarian cancer tissues, which may relate to tumorigenesis and development of epithelial ovarian cancer. Beclin1 overexpression can inhibit proliferation and induce apoptosis of SKOV3 cells. PMID- 17355788 TI - [Mechanism study of antisense cyclin B1 in tumorigenesis inhibition using proteomic technique]. AB - BACKGROUND & OBJECTIVE: Previous researches showed that down-regulating the expression of cyclin B1 in tumor cells by RNA interference may inhibit tumorigenesis, but the mechanism remains to be clarified. This study was to reveal the molecular mechanism of antisense cyclin B1 in tumorigenesis inhibition by comparative proteomic technique. METHODS: A recombinant plasmid containing the full-length antisense cDNA of mouse cyclin B1 was transfected into mouse colon carcinoma cell line CT26. Total proteins of transfected cells and control cells were extracted and separated by two-dimensional gel electrophoresis (2-DE). The differential expression proteins were analyzed with PDQuest software, and identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and Mascot database searching. The 2 differential proteins with the highest confidence of the peptides were selected and verified by Western blot. RESULTS: Seven differentially expressed proteins were identified: Axin2, CCTtheta, DR5, and HPCM27 were up-regulated in transfected cells, while RFP17, mKIAA1195, and LOC77035 were down-regulated. The expression abundance differences of Axin2 and DR5, with the highest confidence, were verified by Western blot. CONCLUSIONS: Several proteins expressed differentially in CT26 cells after transfection of antisense cyclin B1, which take part in some signal pathways in cell proliferation, differentiation, migration, apoptosis, and transcriptional control. The antitumor effect of antisense cyclin B1 may relate to the interplay of the above proteins. PMID- 17355789 TI - [Detection of intracellular and extracellular cytokines of CD4+CD25+ regulatory T cells in gastric cancer patients]. AB - BACKGROUND & OBJECTIVE: CD4+CD25+ regulatory T cells play a crucial role in the immunosuppression of gastric cancer patients, but the mechanism is still unknown. This study was to investigate the secretion of intracellular and extracellular cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-10 and tumor growth factor-beta (TGF-beta) from CD4+CD25+ regulatory T cells in gastric cancer patients, and evaluate their roles in the immunosuppression of gastric cancer. METHODS: Peripheral blood mononuclear lymphocytes of gastric cancer patients were prepared routinely. CD4+CD25+ T cells and CD4+CD25- T cells were isolated by magnetic activated cell sorting (MACS) method, and identified by flow cytometry. The cytokine secretion of CD4+CD25+ T cells and CD4+CD25- T cells was detected by intracellular analysis of cytokine production (IFN-gamma, IL-4 and IL-10) and ELISA (IFN-gamma, IL-10 and TGF-beta). RESULTS: The proportion of CD4+CD25+ T cells to CD4+ T cells was significantly higher in gastric cancer patients than in healthy controls (P<0.05). After 96-hour cell culture, no matter in gastric cancer patients or in healthy controls, the secretion of IL-10 and TGF-beta were significantly higher from CD4+CD25+ T cells than from CD4+CD25- T cells (P<0.05), but the secretion of IFN-gamma was significantly lower from CD4+CD25+ T cells than from CD4+CD25- T cells (P<0.05). CONCLUSION: The immunosuppression of CD4+CD25+ regulatory T cells in gastric cancer may relate to suppressive cytokines, especially TGF-beta. PMID- 17355790 TI - [Correlations of single nucleotide polymorphisms of DNA repair gene XRCC1 to risk of colorectal cancer]. AB - BACKGROUND & OBJECTIVE: X-ray repair cross complementing group 1 (XRCC1) encodes a protein required for DNA base excision repair and single strand break recombination repair. The polymorphisms of XRCC1 affect the function of the protein, therefore, affect the susceptibility of human to cancers. This population-based case-control study was to examine the correlations of the 3 most common single nucleotide polymorphisms (SNPs) of XRCC1 gene, C26304T, G27466A and G28152A, to risk of colorectal cancer. METHODS: XRCC1 genotypes in 207 colorectal cancer patients and 621 matched healthy controls were analyzed by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP). The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model to evaluate the correlations of the 3 genotypes to risk of colorectal cancer. The haplotype distribution was estimated by EH linkage software 1.2. RESULTS: There was no significant differences in selected characteristics, such as age, sex, body mass index, cigarette-smoking and alcohol-drinking status, between the patients and the controls. The frequencies of mutant 26304T, 27466A, and 28152A alleles were 29.95%, 11.22%, and 28.22%, respectively, in the patients, and 32.87%, 12.34%, and 27.27%, respectively, in the controls; there was also no significant difference between the 2 groups. All the polymorphic genotypes met the Hardy-Weinberg equilibrium. No significant correlation of XRCC1 C26304T, G27466A, and G28152A polymorphisms to risk of colorectal cancer was found. Estimated by EH linkage software 1.2, genetic linkage disequilibrium existed both in the patients and the controls, and CGG, CGA, CAG, and TGG were the 4 most common haplotypes. However, there was no significant difference in haplotype distribution between the 2 groups (95.54% vs. 96.64%, P>0.05). CONCLUSIONS: In Han people in southern China, XRCC1 C26304T, G27466A, and G28152A polymorphisms have no correlations to risk of colorectal cancer. However, the genetic linkage disequilibrium exists in these 3 polymorphic sites, and CGG, CGA, CAG, and TGG are the 4 most common haplotypes. PMID- 17355791 TI - [Correlations of XRCC5 polymorphisms to genetic susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a high incidence region]. AB - BACKGROUND & OBJECTIVE: XRCC5 is a repair gene for DNA double-strand break. Its abnormal expression and dysfunction is correlated to tumorigenesis and development. This study was to investigate the correlations of XRCC5 polymorphisms to genetic susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of high incidence region, Cixian and Shexian counties of Hebei Province, China. METHODS: The genotypes of XRCC5 single nucleotide polymorphisms (SNPs), C74468A and G74582A, in 329 ESCC patients, 255 GCA patients, and 631 healthy controls were detected by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The overall genotype and allelotype distributions of XRCC5 C74468A and G74582A in ESCC and GCA patients were not significantly different from those in healthy controls (P>0.05). When stratified by smoking status and family history of upper gastrointestinal cancer (UGIC), A allele (A/C+A/A genotype) of C74468A significantly reduced the risk of developing ESCC and GCA in positive UGIC family history group [age, sex, and smoking status adjusted odds ratios (ORs) were 0.58 and 0.61, 95% confidence intervals (CIs) were 0.38-0.90 and 0.38-0.97, respectively]u G allele (A/G+G/G genotype) of G74582A significantly reduced the risk of developing GCA in positive UGIC family history group (age, sex, and smoking status adjusted OR=0.63, 95% CI=0.40-0.98). Combined analysis of the 2 XRCC5 SNPs showed that the haplotype distribution in ESCC and GCA patients was also not significantly different from that in healthy controls (P> 0.05). CONCLUSIONS: In the population with positive UGIC family history in the high incidence region of Hebei Province, individuals with A allele of XRCC5 C74468A might have low risk of developing ESCC and GCA, however, individuals with G allele of XRCC5 G74582A might only have low risk of developing GCA. PMID- 17355792 TI - [Sparing normal oral tissues with individual dental stent in radiotherapy for primary nasopharyngeal carcinoma patients]. AB - BACKGROUND & OBJECTIVE: With the progression of radiotherapy techniques, the 5 year overall survival rate of nasopharyngeal carcinoma (NPC) patients has increased obviously. As the survival time prolonged, more and more attention was paid to various radiation sequelae and the quality of life of the patients. This study was to explore the role of individual dental stent in sparing normal oral tissues for primary NPC patients in radiotherapy by pushing the tongue and a part of oral mucous membrane away from the radiation fields. METHODS: Irradiation dose and volume of the tongue of a NPC patient before and after wearing dental stent was evaluated. A total of 43 patients were randomized into 2 groups: 19 in trial group and 24 in control group. Trial group wore dental stent during radiotherapy, while control group did not. Patients' weight, taste, oral mucous reaction, and tongue mucous reaction before radiotherapy and every week during radiotherapy were examined. RESULTS: Dosimetric analysis proved that the irradiation dose and volume of the tongue decreased obviously in trial group. The occurrence rate of grade 1-2 mucositis of the oral cavity was higher in trial group than in control group (73.68% vs. 62.50%), but the occurrence rate of grade 3-4 mucositis was lower in trial group than in control group (26.32% vs. 37.50%, P=0.470). By the completion of radiotherapy, 4 (21.05%) patients in trial group and 19 (79.17%) in control group suffered from taste dysfunction (P<0.001). CONCLUSION: Individual dental stent is useful in sparing the oral mucous membrane and preserving taste for primary NPC patients in radiotherapy. PMID- 17355793 TI - [Preservation of the saphenous vein during inguinal lymphadenectomy for vulval malignancies]. AB - BACKGROUND & OBJECTIVE: The conventional operation for the patients with vulval malignancies is radical vulvectomy and bilateral inguinal lymphadenectomy with partial saphenous vein trunk ligation and resection, but the quality of life of the patients was declined severely because of multiple postoperative complications. This study was to explore the influences of preserving the saphenous vein during inguinal lymphadenectomy for vulval malignancies on operation, prognosis, and complications. METHODS: A total of 64 patients with vulval malignancies, treated in Shandong Provincial Cancer Hospital from Jan. 1989 to Dec. 2005, were divided into 2 groups: the saphenous vein was preserved in 31 patients and ligated in 33 patients during inguinal lymphadenectomy. The operating time, intraoperative blood loss, 5-year survival rate, recurrence rate, and complications were compared between the 2 groups. RESULTS: The median operating time of bilateral inguinal lymphadenectomy was 155 min (130-170 min) in preservation group, and 140 min (120-170 min) in ligation group (P>0.05). The median intraoperative blood loss was 295 ml (100-450 ml) in preservation group, and 270 ml (150-390 ml) in ligation group (P>0.05). The 5-year overall survival rate was 67.3%u it was 68.0% in preservation group and 66.7% in ligation group (P>0.05). Till Mar. 2006, 5 sides of inguinal lymph nodes relapsed in 3 patients in preservation group, and 7 sides in 5 patients in ligation group; the recurrence rates were 8.9% (5/56), and 12.1% (7/58) (P>0.05). The occurrence rates of acute low extremity lymph edema, low extremity phlebitis, chronic low extremity edema, and chronic leg pain were significantly lower in preservation group than in ligation group (11.3% vs. 25.8%, P<0.05; 43.5% vs. 66.7%, P<0.01; 25.0% vs. 48.3%, P<0.01; 23.2% vs. 46.6%, P<0.01); the occurrence of leg cellulitis and sense abnormity were also less in preservation group than in ligation group (P<0.05). CONCLUSIONS: Preserving the saphenous vein trunk during inguinal lymphadenectomy for vulval malignancies reduces multiple postoperative complications without compromising treatment outcome. This modified operative modality is valuable to be recommended. PMID- 17355794 TI - [Correlation of hepatitis B virus infection to non-Hodgkin's lymphoma]. AB - BACKGROUND & OBJECTIVE: Previous studies showed that the infection rate of hepatitis B virus (HBV) is higher in non-Hodgkin's lymphoma (NHL) patients than in non-primary liver cancer solid tumor patients and general population in the same region, but the correlation of HBV infection to NHL is inconclusive. This study was to compare HBV infection rate of NHL patients with that of non-primary liver cancer solid tumor patients, and explore the correlation of HBV infection to NHL. METHODS: The infection of hepatitis B virus surface antigen (HBsAg) in 109 NHL patients and 128 colorectal carcinoma patients was detected. The positive rates of HBsAg in the patients and general population were compared by Chi-square test. RESULTS: The positive rate of HBsAg was significantly higher in NHL patients than in colorectal carcinoma patients and general population (40.4% vs. 14.1% and 17.3%, P<0.01). Regarding colorectal carcinoma patients as a reference group, odds ratio (OR) of NHL in HbsAg-positive population was 2.87, and the 95% confidence interval (95% CI) was 1.830-4.502. CONCLUSION: The positive rate of HBsAg is higher in NHL patients than in colorectal carcinoma patients and general population. PMID- 17355795 TI - [Correlation of CXCR4/CXCL12 overexpression to lymph node metastasis and chronic inflammation in cervical adenocarcinoma]. AB - BACKGROUND & OBJECTIVE: CXCL12 is a kind of chemokine. CXCR4, the specific receptor of CXCL12, is involved in metastasis of tumors. CXCR4/CXCL12 expression in cervical adenocarcinoma has seldom been reported. This study was to investigate the correlation of CXCR4/CXCL12 overexpression to lymph node metastasis and chronic inflammation in cervical adenocarcinoma. METHODS: CXCR4 and CXCL12 immunohistochemical staining and HE staining were performed in 35 specimens of cervical adenocarcinoma, including 8 with lymph node metastasis and 27 without. Marked expression of CXCR4 or CXCL12 observed in more than 90% tumor cells was defined as overexpression. Fisher's exact test, Chi-square test, and Pearson correlation test were used to analyze the results. RESULTS: All 35 specimens of cervical adenocarcinoma expressed CXCR4. The overexpression rate of CXCR4 was significantly higher in the cases with lymph node metastasis than in those without (62.50% vs. 22.00%, P<0.05), slightly higher in the IB cases with lymph node metastasis than in those without (33.33% vs. 26.01%, P>0.05), and significantly higher in the IIB cases with lymph node metastasis than in those without (80.00% vs. 0.00%, P<0.05). The positive predictive value of CXCR4 overexpression to assess lymph node metastasis was 45.45%, and the negative predictive value was 87.50%. A variable number of tumor cells in 33 specimens expressed CXCL12. The overexpression rate of CXCL12 was significantly higher in IB cases than in IIB cases either in tumors with lymph node metastasis (0.00% vs. 80.00%, P<0.05) or without (21.73% vs. 75.00%, P<0.05). CXCR4 overexpression was positively correlated to CXCL12 overexpression in the 23 IB cases without lymph node metastasis; but the correlation did not exist in the 3 IB cases with lymph node metastasis and the 9 IIB cases. All the 35 specimens were accompanied with chronic inflammation; the infiltrates were mainly lymphocytes. CXCL12 overexpression was not correlated to the infiltration degree of chronic inflammation. CONCLUSIONS: CXCR4 overexpression indicates a higher lymph node metastasis potential of cervical adenocarcinoma. The overexpression rate of CXCL12 is increasing by the progression of tumors. The chronic inflammatory cells in cervical adenocarcinoma are not attracted by CXCL12. PMID- 17355796 TI - [Appropriate extent of lymph node dissection for clinical I a stage non-small cell lung cancer]. AB - BACKGROUND & OBJECTIVE: There is no agreement on the appropriate extent of lymph node dissection for lung cancer, especially for early non-small cell lung cancer (NSCLC). This study was to explore the appropriate extent of lymph node dissection for early NSCLC by investigating the metastasis regulations of hilar and mediastinal lymph nodes. METHODS: Forty-one clinical Ia stage NSCLC patients received lobectomy and systematic mediastinal lymphadenectomy in Tongji Hospital from Jan. 2002 to Dec. 2004. The removed lymph nodes were subjected for pathologic examination. The metastasis regulations of hilar and mediastinal lymph nodes were investigated. RESULTS: A total of 295 groups of lymph nodes were removed. Among them, 42 (14.2%) groups had metastasis, including 33 groups of hilar lymph nodes and 9 of mediastinal lymph nodes. Four patients had mediastinal lymph node metastasis in the 7th station, 2 in the 5th station, 2 in the 9th station, and 1 in the 4th station. The patients with tumors in the upper lobe had metastasis in the 5th or 7th station lymph nodes; the patients with tumors in the middle or lower lobe had metastasis in the 4th, 7th, or 9th station. CONCLUSIONS: The metastasis regulations of hilar and mediastinal lymph nodes in Ia stage NSCLC is accordant to regional lymph node drainage regulations. Selective regional lymph node dissection might be applied in these patients, that is, upper mediastinal lymph node, not lower mediastinal lymph node, should be removed when the tumor is in the upper lobe without hilar or subcarinal lymph node metastasis, while all mediastinal lymph nodes should be removed when the tumor is in the middle or lower lobe. PMID- 17355797 TI - [Ivor Lewis esophagectomy with two-field lymph node dissection for squamous cell carcinoma of the lower thoracic esophagus]. AB - BACKGROUND & OBJECTIVE: Esophagectomy with local regional lymph node dissection is the main treatment for lower thoracic esophageal carcinoma. This study was to assess the clinical outcomes of Ivor Lewis esophagectomy with two-field lymph node dissection for squamous cell carcinoma of the lower thoracic esophagus. METHODS: Clinical data of 73 patients with squamous cell carcinoma of the lower thoracic esophagus, who underwent Ivor Lewis esophagectomy with two-field lymph node dissection from Jan. 1998 to Dec. 2001, were analyzed retrospectively. Kaplan-Meier method was used for survival analysis. RESULTS: The morbidity of postoperative complications was 15.1% with a 2.7% mortality rate. The lymph node metastasis rate was 71.2%; the metastasis rate of the upper mediastinal nodes was 17.8%. Of the 73 patients, 5 were at stage I, 35 at stage II, 32 at stage III, and 2 at stage IV. The overall 5-year survival rate was 23.3%. The 5-year survival rate was 38.1% for N0 patients and 17.3% for N1 patients (P<0.01), and was 31.2% for stage IIa patients, 27.8% for stage IIb patients, and 12.5% for stage III patients (P<0.01). CONCLUSION: Ivor Lewis esophagectomy with two-field lymph node dissection for squamous cell carcinoma of the lower thoracic esophagus is a safe operation, and may increase the chances of complete resection. PMID- 17355798 TI - [Expression and clinical significance of uPA and PAI-1 in epithelial ovarian cancer]. AB - BACKGROUND & OBJECTIVE: Recent researches showed that urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor (PAI)-1, play an important role in the invasion and metastasis of solid tumors. However, their correlations to epithelial ovarian cancer have seldom been reported. This study was to investigate the roles of uPA and PAI-1 in the invasion and metastasis of epithelial ovarian cancer, to clarify their localization and relationship with prognosis. METHODS: Immunohistochemistry was applied to examine the protein expression of uPA and PAI-1 in 80 specimens of epithelial ovarian cancer and 20 specimens of benign ovarian tumor. The correlations of their expression to the clinicopathologic characteristics and prognosis of the patients were analyzed. RESULTS: The positive rates of uPA and PAI-1 were significantly higher in epithelial ovarian cancer than in benign ovarian tumor (77.5% vs. 30.0%, P<0.001; 55.0% vs. 20.0%, P=0.005). uPA expression was correlated positively to PAI-1 expression in epithelial ovarian cancer (P=0.001). Higher positive rate of uPA was associated with greater metastatic tumor in the peritoneal cavity (P=0.038), but not associated with age, FIGO stage, histological type, pathologic grade, serum CA125 level, ovarian tumor size, and the size of residual tumor (P>0.05). Higher positive rate of PAI-1 was associated with early FIGO stage (P=0.022), but not associated with other parameters (P>0.05). Multivariate analysis showed that uPA was an independent factor for progression-free survival and overall survival, and PAI-1 was an independent factor for overall survival. CONCLUSION: Both uPA and PAI-1 are up-regulated in epithelial ovarian cancer, and might be used as markers to predict the prognosis of epithelial ovarian cancer patients. PMID- 17355799 TI - [Experiences of diagnosing and treating atypical renal angiomyolipoma--a report of 22 cases]. AB - BACKGROUND & OBJECTIVE: Renal angiomyolipoma (RMAL) is a benign renal tumor. The patients could be rechecked regularly or treated with operation. The result of operation is good. But the atypical cases are easy to be misdiagnosed. This study was to summarize our experiences of diagnosing and treating atypical RMAL. METHODS: Clinical data of 22 atypical RMAL patients, treated in Cancer Center of Sun Yat-sen University from Jan. 1999 to Nov. 2005, were analyzed. RESULTS: Of the 22 cases of atypical RMAL, 7 were misdiagnosed as renal carcinoma, and treated with radical nephrectomy (6 cases) and nephron-sparing operation (1 case)u 1 was misdiagnosed as renal pelvic carcinoma, and treated with radical resection; 14 were correctly diagnosed through analyzing the image information of computed tomography (CT), B-ultrasound (B-US), magnetic resonance imaging (MRI), intravenous urography (IVU), and contrast-enhanced ultrasound, and treated with nephron-sparing operation (9 cases) and nephrectomy (3 cases), or were rechecked during follow-up (2 cases). All cases were confirmed as RMAL by postoperative pathology. No local relapse occurred during follow-up. CONCLUSIONS: Careful analysis of image information can help to avoid misdiagnosis of atypical RMAL. The prognosis of RMAL after appropriate treatment is good. PMID- 17355800 TI - [Application of total intravenous anesthesia with remifentanyl and propofol to radiofrequency ablation]. AB - BACKGROUND & OBJECTIVE: Percutaneous radiofrequency ablation (PRFA) is a new and effective microinvasive operation for small hepatocellular carcinoma, but the effect of local anesthesia or single analgesic injection as regular anesthesia is unsatisfied. This study was to evaluate the efficacy and safety of continuous intravenous infusion of remifentanyl combined with propofol as total intravenous anesthesia during PRFA. METHODS: Sixty patients scheduled for PRFA were randomized into remifentanyl group (R) and fentanyl group (F). Each group contained 30 patients. Group R received remifentanyl infusion at the dose of 0.1 microg x kg(-1) x min(-1) by micro pump; group F received bolus intravenous injection of fentanyl at 1.5 microg x kg(-1) before operation. Anesthesia was maintained with propofol. The mean arterial pressure (MAP), heart rate (HR), pulse oxygen saturation (SPO2), respiration rate (RR), partial pressure of carbon dioxide in artery (PaCO2) and recovery time were measured and recorded by monitor. The limb movement, apnea, body movements, and chest wall rigidity were recorded during operation. RESULTS: The recovery time of group R was significantly shorter than that of group F [(5.0+/-1.8) min vs. (10.7+/-3.0) min, P<0.001]; the total consumption of propofol was less in group R than in group F [(172.0+/-37.3) mg vs. (330.3+/-61.2) mg, P<0.001]. Group R had less cases with limb movement (5 cases vs. 12 cases) but more cases with apnea (12 cases vs. 6 patients) as compared with group F. CONCLUSIONS: Total intravenous anesthesia with remifentanyl and propofol for PRFA is safe and reliable. Respiratory depression should be monitored instantly and strictly. PMID- 17355801 TI - [Treatments and outcomes of 10 cases of subglottic cancer and literature review]. AB - BACKGROUND & OBJECTIVE: Subglottic cancer is rare. The subglottic region of the larynx is occult, which leads to misdiagnosis or missed diagnosis of subglottic cancer. It is usually advanced when initially presented. There is no large amount case-control study on subglottic cancer, and management of this tumor is still controversial. This study was to analyze the clinical features, treatments, and outcomes of subglottic cancer. METHODS: Clinical records of 10 subglottic cancer patients, treated in Cancer Center of Sun Yat-sen University from Jan. 1981 to Oct. 2005, were reviewed. RESULTS: Of the 10 patients, 4 had intralaryngeal invasion of more than half circle, 4 had extralaryngeal invasion, and 1 had lymph node metastasis. The patients were followed up for 1-15 years; 1 was lost. The overall 5-year survival rate was 55.5% (5/9). Excepted for the 2 patients denied treatment, the 5-year survival rate of the 7 treated patients was 71.4%, the 5 year disease-free survival rate was 42.9%. The 5-year disease-free survival was 0/2 for the patients received radiotherapy alone, 1/2 for those received operation alone, and 2/3 for those received both treatments. CONCLUSIONS: Subglottic cancer is usually advanced when diagnosed, and tends to extend within the larynx and infiltrate other organs. The prognosis is poor. Total laryngectomy is still the main operation for subglottic cancer, and operation combined with radiotherapy is better than single treatment. PMID- 17355802 TI - [Preparation of anti-human indoleamine 2,3-dioxygenase polyclonal antibody]. AB - BACKGROUND & OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO), a cytosolic hemoprotein, catalyzes the rate-limiting step in tryptophan catabolism along the kynurenine pathway in mammals, arrests the growth of pathogens, and suppresses T cell responses, therefore, leads to IDO-dependent tumor immune tolerance. This study was to express and purify His-hIDO fusion protein and to generate rabbit anti-human IDO polyclonal antibody, which was used to analyze IDO expression in tumor cells. METHODS: Human IDO cDNA was cloned into pET30a(+). The recombinant vector pET30a(+)-hIDO was transformed into BL21 after sequencing. The expression of His-hIDO protein was induced by IPTG. The anti-human IDO polyclonal antibody was obtained by immunizing rabbits with purified His-hIDO protein. The quality of the antibody was identified by Western blot. IDO expression in human fibroblast cancer cell line A431 and liver cancer cell line HepG2 induced by interferon gamma (IFN-gamma) was also analyzed using the antibody. RESULTS: His-hIDO fusion protein was specifically combined with His-probe polyclonal antibody. The rabbit anti-human IDO polyclonal antibody was of high titer with high specificity. It could recognize IDO expression induced by IFN-gamma in A431 and HepG2 cells. CONCLUSION: The rabbit anti-human IDO polyclonal antibody could recognize IDO expression in tumor cells in vitro effectively, therefore, provides a tool to study the role of IDO in tumor immune tolerance. PMID- 17355803 TI - [Prothymosin alpha and tumor: current status and perspective]. AB - Prothymosin alpha (ProTalpha) is a small molecule of natively unstructured acidic protein, and widely exists in mammalian tissues. Nevertheless, its biological functions are still elusive. Recent studies indicate that ProTalpha is involved in carcinogenesis and cancer development. We reviewed current reports on the potential roles of ProTalpha in cell proliferation, carcinogenesis, apoptosis, and immunomodulatory, discussed the regulation of ProTalpha gene expression and possible molecular mechanisms underlying its internal and external actions in cells, and explored its significance in tumor diagnosis and treatment. PMID- 17355804 TI - In support of geriatric dentistry at the undergraduate level. PMID- 17355805 TI - Oral health related quality of life and its association with sociodemographic and clinical findings in 3 northern outreach clinics. AB - OBJECTIVE: Aspects of oral health related quality of life (OHQOL) are attracting increased attention in dentistry. Knowledge in this field is limited, especially in terms of significant indicators and predictors of impaired OHQOL. The aim of this cross-sectional study was to examine the influence of various sociodemographic and clinical variables on OHQOL in the setting of outreach clinics in northern Alberta, Canada. METHODS: OHQOL was measured with the 49-item Oral Health Impact Profile questionnaire (OHIP-49), administered to adult patients attending 3 dental outreach clinics managed by the University of Alberta. Sociodemographic and clinical data were also collected. Data were analyzed using descriptive and multivariable methods. RESULTS: The OHIP-49 scores were comparatively low for a patient sample. After multivariable stepwise logistic regression analysis, only gender, missing anterior teeth and need for endodontic treatment remained as significant variables in the final model for impaired OHQOL. Missing anterior teeth (regardless of replacement) had the strongest effect. Subjects with this feature had an approximately 21-fold greater risk of impaired OHQOL relative to those who retained all of their anterior teeth. CONCLUSIONS: The clientele of these outreach clinics was generally young but had high treatment needs. OHQOL results can be useful in considering treatment strategies in similar rural environments, but the complexity of this indicator necessitates an individual patient-centred approach in clinical decision-making. PMID- 17355806 TI - Smoking and oral health status. AB - Clinical studies suggest that smokers have a higher than average risk of periodontal disease and poor oral health status. In 2003, the Canadian Community Health Survey--a multistage, nationwide household survey--asked a series of questions related to oral health status. This report is based on the population aged 18 and older who answered the optional module on oral health (33,777 respondents). This subsample represents a weighted population of 23.9 million. The overall survey response rate was 80.6%.In our sample, 24% of respondents were current cigarette smokers, 43% were former smokers and 33% had never smoked. The prevalence of current smoking declined with advancing age and was inversely associated with household income and level of education. The prevalence of edentulism was 15% among current smokers compared with 7% among those who had never smoked. In the dentate population, current smokers were less likely to have visited a dentist in the past 3 years and more likely to report sensitivity of teeth, tooth ache in the previous month, pain in the mouth or face and social limitations because of teeth. When age, sex, household income and dental insurance were controlled in a multivariate logistic regression model, current smokers and former smokers had higher odds of reporting oral-facial pain than people who had never smoked. Prevention of smoking onset and support for cessation of smoking could contribute to improved oral health status. PMID- 17355807 TI - Review and revision of the competencies for a beginning dental practitioner in Canada. AB - In 1994, the first dental competency document developed at a national level was adopted in Canada by all stakeholders. As a result of a recommendation made by the consensus workshop involved in the original process, a 10-year review and revision of the competencies for a beginning dental practitioner in Canada was undertaken and completed. As of November 2005, the revised competencies have been adopted by all stakeholders and are being used as a reference for curriculum management, program accreditation and the development of certification examinations. PMID- 17355808 TI - Sympathetically maintained pain presenting first as temporomandibular disorder, then as parotid dysfunction. AB - Complex regional pain syndrome (CRPS) is a chronic condition characterized by intense pain, swelling, redness, hypersensitivity and additional sudomotor effects. In all 13 cases of CRPS in the head and neck region reported in the literature, nerve injury was identified as the etiology for pain initiation. In this article, we present the case of a 30-year-old female patient with sympathetically maintained pain without apparent nerve injury. Her main symptoms- left-side preauricular pain and inability to open her mouth wide--mimicked temporomandibular joint arthralgia and myofascial pain of the masticatory muscles. Later, symptoms of intermittent preauricular pain and swelling developed, along with hyposalivation, which mimicked parotitis. After an extensive diagnostic process, no definitive underlying pathology could be identified and a diagnosis of neuropathic pain with a prominent sympathetic component was made. Two years after the onset of symptoms and initiation of care, treatment with repeated stellate ganglion blocks and enteral clonidine pharmacotherapy provided adequate pain relief. PMID- 17355809 TI - Large erupting complex odontoma: a case report. AB - Odontomas are the most common odontogenic tumours. They are usually asymptomatic and are often discovered during routine radiography. We report a case of a large erupting complex odontoma that caused pain, infection and facial asymmetry. This case is significant as there are few reports of complex odontoma erupting in the oral cavity. PMID- 17355810 TI - Chondrosarcoma of the mandible: a case report. AB - Chondrosarcomas are malignant tumours of cartilaginous origin. They range from a well-differentiated growth resembling a benign cartilage tumour to a high-grade malignancy with aggressive local behaviour and the potential to metastasize. Only 5% to 10% of chondrosarcomas are known to occur in the head and neck region. A case of chondrosarcoma of the anterior region of the mandible is presented, along with a review of the relevant literature. PMID- 17355811 TI - Confinement of dynamical chaos expansion in rotifer populations inhabiting heterogeneous environments: an effect of attractor size invariance. AB - We study the impact of inter-habitat interactions in rotifer populations with intrinsically different types of dynamics: chaotic and regular. For this purpose we use a modified version of the Consensus model. The Consensus model has been shown to be realistic enough to reproduce distinguishing features of the rotifer species dynamics. Being uncoupled, a habitat with chaotic dynamics and habitats with regular oscillations of the rotifer density do not affect each other. Migration of the rotifers between the habitats leads to the invasion of chaos into neighboring habitats, that is chaotic rotifer oscillations replace regular oscillations of the rotifer density in neighboring habitats. The invasion of chaos distorts spatial borders of the rotifer oscillations synchronization clusters. We show that the invasion of chaos is spatially confined. Invariance of the attractor size under transformation of regular oscillations into chaotic ones is demonstrated to be responsible for the chaos confinement. PMID- 17355812 TI - Modeling cell dynamics under mobile phone radiation. AB - Perturbations by pulse-modulated microwave radiation from GSM mobile phones on neuron cell membrane gating and calcium oscillations have been suggested as a possible mechanism underlying activation of brain states and electroencephalographic epiphenomena. As the employ of UMTS phones seems to reveal other symptoms, a unified phenomenological framework is needed. In order to explain possible effects of mobile phone radiation on cell oscillations, GSM and UMTS low-frequency envelopes have been detected, recorded and used as input in cell models. Dynamical systems endowed with contiguous regular and chaotic regimes suitable to produce stochastic resonance can both account for the perturbation of the neuro-electrical activity and even for the low intensity of the signal perceived by high sensitive subjects. Neuron models of this kind can be employed as a reductionist hint for the mentioned phenomenology. The Hindmarsh Rose model exhibits frequency enhancement and regularization phenomena induced by weak GSM and UMTS. More realistic simulations of cell membrane gating and calcium oscillations have been performed with the help of an adaptation of the Chay Keizer dynamical system. This scheme can explain the suspected subjective sensitivity to mobile phone signals under the thermal threshold, in terms of cell calcium regularity mechanisms. Concerning the two kinds of emission, the stronger occupation of the ELF band of last generation UMTS phones is compensated by lower power emitted. PMID- 17355813 TI - The dynamics of structural and functional complexity across the lifespan. AB - The paper addresses the process of human physiological development and aging from the perspective complexity at the structural level and functional levels. The goal is to present a view of the human lifespan as a continuous increase in structural complexity of the human system, resulting in increased independence of the physiological subsystems. This brings about an increase in functional complexity early in the lifespan and an eventual loss of complexity during human aging (Lipsitz & Goldberger, 1995). Different nonlinear dynamics concepts are presented as a means of providing support for this theory of human aging and development. PMID- 17355814 TI - A swallowtail catastrophe model for the emergence of leadership in coordination intensive groups. AB - This research extended the previous studies concerning the swallowtail catastrophe model for leadership emergence to coordination-intensive groups. Thirteen 4-person groups composed of undergraduates played in Intersection coordination (card game) task and were allowed to talk while performing it; 13 other groups worked nonverbally. A questionnaire measured leadership emergence at the end of the game along with other social contributions to the groups' efforts. The swallowtail catastrophe model that was evident in previous leadership emergence phenomena in creative problem solving and production groups was found here also. All three control parameters were identified: a general participation variable that was akin to K in the rugged landscape model of self-organization, task control, and whether the groups worked verbally or nonverbally. Several new avenues for future research were delineated. PMID- 17355815 TI - Transition of chaotic motion to a limit cycle by intervention of economic policy: an empirical analysis in agriculture. AB - This paper investigates the transition of dynamics observed in an actual real agricultural economic dataset. Lyapunov spectrum analysis is conducted on the data to distinguish deterministic chaos and the limit cycle. Chaotic and periodic oscillation were identified before and after the second oil crisis, respectively. The statitonarity of the time series is investigated using recurrence plots. This shows that government intervention might reduce market instability by removing a chaotic market's long-term unpredictability. PMID- 17355816 TI - Chaotic Footloose Capital. AB - This paper examines the long-term behavior of a discrete-time Footloose Capital model, where capitalists, who are themselves immobile between regions, move their physical capital between regions in response to economic incentives. The spatial location of industry can exhibit cycles of any periodicity or behave chaotically. Long-term behavior is highly sensitive to transport costs and to the responsiveness of capitalists to profit differentials. The concentration of industry in one region can result from high transport costs or from rapid responses by capitalists. In terms of possible dynamical behaviors, the discrete time model is much richer than the standard continuous-time Footloose Capital model. PMID- 17355817 TI - QT hysteresis in long-QT syndrome children with exercise testing. AB - BACKGROUND: Congenital long QT syndrome (LQTS) is an inherited ion channel disorder resulting in abnormal cardiac repolarization that can cause syncope and sudden death associated with a prolonged rate-corrected QT interval and polymorphic ventricular tachycardia. Several studies in adults showed that LQTS patients have altered QT adaptation to heart rate changes compared with normal subjects which forming a "hysteresis loop" in the QT-circle length plot. This study was to observe the QT interval changing during exercise testing in children long QT syndrome (LQTS) patients, explore the new diagnosis methods of LQTS. METHODS: The subjects were divided into 3 groups according to 1993 LQTS diagnostic criteria. Group 1: LQTS group (n = 17) who scored > or = 4 points indicating definite LQTS. Group 2: Middle group (n = 16), patients who have prolonged QT interval but scored 1.5 to 3.5. Group 3: Normal control group (n = 18). The average age of all study population is (12.3 +/- 5.8) years. No case had beta-adrenergic antagonists administration before exercise testing. All subjects were underwent tread mill exercise testing and electrocardiograph in whole exercise testing and recovery were recorded. QT and heart rate changing during whole exercise testing period were recorded. DeltaQT, the QT interval at 1, 2, 4, 6 minutes into recovery subtract from the QT interval at a similar heart rate during exercise, were calculated. RESULTS: In all three groups, QT intervals were shortening with the increasing of heart rate, but QTc had no significant change. DeltaQT at 1 minute ((45 +/- 11) ms), 2 minutes ((37 +/- 15) ms), 4 minutes ((23 +/- 12) ms) into recovery in LQTS group were significantly greater than that of the other two groups (P < 0.05, P < 0.01, P < 0.01, respectively). There was no DeltaQT significant difference between middle group and normal control group at recovery time. During the recovery phase in LQTS group, the QT interval remained shortened despite a decelerating heart rate, forming a hysteresis "loop" in the curve relating the QT interval to the cycle length. CONCLUSIONS: In children LQTS patients, there is significant QT hysteresis loop in the relation of QT interval with heart rate during recovery of exercise testing, which could be useful to the early diagnosis for LQTS. PMID- 17355818 TI - Short and long-term outcomes of two drug eluting stents in bifurcation lesions. AB - BACKGROUND: Because no large prospective studies are available, this study evaluated the clinical outcomes of two drug eluting stents in bifurcation lesions. METHODS: Lesions with diameter of side branch = 2.5 mm were selected. From October 2003 to June 2005, 112 patients with 113 bifurcation lesions were treated by two drug eluting stents (DESs), technique. The location of bifurcation lesions were left anterior descending coronary artery/diagonal in 62 patients, left main distal bifurcation in 32, left circumflex coronary artery/obtute marginal branch in 18 and right coronary artery distal bifurcation in 1. Procedures for bifurcation lesions were crush or modified crush technique in 64, "T" stenting technique in 27, modified "Y" stenting, kiss stenting, "V" stenting as well as culotte stenting technique in 11, 5, 3 and 3, respectively. Among 226 lesions, 91 Cypher or Cypher select stents, 74 TAXUS and 67 Firebird were used. Final kiss balloon dilation was performed in 60 (93.7%) with crush technique after stenting. RESULTS: Success rate of percutaneous coronary intervention for the bifurcation lesions was 100%. One patient, who developed inhospital acute myocardial infarction due to subacute thrombosis, was successfully treated by a second intervention. Major adverse cardiac events rate in-hospital was 0.89% (1/112) and during followup was 7.14% (8/112). No death occurred during the followup of all patients. Angiographic followup was effected for 46 patients, restenosis for eight, coronary artery bypass grafting for 1 and a repeat intervention for 5. Restenosis involving TAXUS, Cypher and Firebird was 5 (5/18, 27.8%), 2 (2/17, 11.8%) and 1 (1/11, 9.1%), respectively (P > 0.05). Total restenotic rate was 17.4% (8/46). CONCLUSIONS: When ostium of side branch has severe stenosis and >or= 2.5 mm in diameter, two-stent strategy in this bifurcation lesion is safe and effective, and the outcomes are satisfactory. Restenotic rates were not different between TAXUS, Cypher and Firebird DESs. PMID- 17355819 TI - Changes in expression of adrenomedullin in the myocardium of streptozotocin induced diabetic rats. AB - BACKGROUND: Adrenomedullin is a potent vasodilating peptide and involved in many cardiovascular diseases. However, whether adrenomedullin is involved in the pathogenesis of diabetic cardiomyopathy is still unknown. Our aim was to characterize the expression pattern of adrenomedullin in the myocardium of streptozotocin-induced diabetic rats. METHODS: The weight, blood glucose, and urine glucose of 20 streptozotocin-induced diabetic rats were measured before and after model induction in the diabetic and control groups. The alteration of the adrenomedullin expression was explored in the left ventricular myocardium in both groups by immunohistochemistry. Changes in heart ultrastructure were also analyzed by using hemotoxylin and eosin staining and transmission electron microscopy. All data were analyzed by the independent samples t test. RESULTS: The data of weight, blood glucose, and urine glucose had no significant difference between the control and the diabetic groups before animal model induction. Four weeks after the induction of diabetes, the differences between the two groups in weight, blood glucose, and urine glucose were distinct. When compared with the control group, the diabetic group showed ultrastructural changes including hypertrophy, fibrosis, myofibrillar disarrangements, mitochondrial disruption, and increase in nuclear membrane invaginations. A significant decrease of adrenomedullin expression was also observed in cardiac myocytes of the diabetic rats (P < 0.01). CONCLUSIONS: Our study provides experimental evidence that hyperglycemia could damage cardiac myocytes. Down regulation of cardioprotective peptide adrenomedullin in the myocardium of streptozotocin-induced diabetic rats may contribute to the diabetic cardiomyopathy and left ventricular dysfunction. PMID- 17355820 TI - Passive graft perfusion in off-pump coronary artery bypass grafting. AB - BACKGROUND: Myocardial protection during off-pump coronary artery bypass grafting (OPCABG) is a multifactorial problem in which maintaining stable systemic hemodynamics is very important. In this study passive graft perfusion (PGP) was applied to investigate the effect during and after OPCABG as evaluated by cardiac troponin I (CTnI) and hemodynamic indexes. METHODS: Thirty first-time patients underwent OPCABG under one surgeon. They were randomly divided into two groups: The passive graft perfusion group (PGP, n = 15) received distal coronary perfusion during the anastomosis and immediate graft perfusion after the distal anastomosis. The control group, no graft perfusion group, (NGP, n = 15) received no graft perfusion after the distal anastomosis. The results of the two protocols were evaluated by concentration of CTnI and hemodynamic indexes before induction and after operation. RESULTS: There were no statistically significant differences between these two groups in their perioperation parameters. The level of CTnI increased postoperatively, reached its peak at 6 hours (P < 0.05) and recovered by the 6 days postoperative. Compared with the control group the concentration of CTnI in the PGP group was significantly lower at 6 and 24 hours (P < 0.01). Compared with the NGP group, cardiac index (CI) in the PGP group was higher at 12 and 24 hours after operation (P < 0.05). The period of mechanical ventilation was significantly shorter in the PGP group than in the NGP group (P < 0.05). CONCLUSION: PGP can increase the flow to the myocardium and shorten the heart ischemia time, thus maintain stable systemic hemodynamics, supply a satisfactory CI after surgery and improve surgery outcome. PMID- 17355821 TI - Biodegradable chitosan scaffolds containing microspheres as carriers for controlled transforming growth factor-beta1 delivery for cartilage tissue engineering. AB - BACKGROUND: Natural articular cartilage has a limited capacity for spontaneous regeneration. Controlled release of transforming growth factor-beta1 (TGF-beta1) to cartilage defects can enhance chondrogenesis. In this study, we assessed the feasibility of using biodegradable chitosan microspheres as carriers for controlled TGF-beta1 delivery and the effect of released TGF-beta1 on the chondrogenic potential of chondrocytes. METHODS: Chitosan scaffolds and chitosan microspheres loaded with TGF-beta1 were prepared by the freeze-drying and the emulsion-crosslinking method respectively. In vitro drug release kinetics, as measured by enzyme-linked immunosorbent assay, was monitored for 7 days. Lysozyme degradation was performed for 4 weeks to detect in vitro degradability of the scaffolds and the microspheres. Rabbit chondrocytes were seeded on the scaffolds containing TGF-beta1 microspheres and incubated in vitro for 3 weeks. Histological examination and type II collagen immunohistochemical staining was performed to evaluate the effects of released TGF-beta1 on cell adhesivity, proliferation and synthesis of the extracellular matrix. RESULTS: TGF-beta1 was encapsulated into chitosan microspheres and the encapsulation efficiency of TGF beta1 was high (90.1%). During 4 weeks of incubation in lysozyme solution for in vitro degradation, the mass of both the scaffolds and the microspheres decreased continuously and significant morphological changes was noticed. From the release experiments, it was found that TGF-beta1 could be released from the microspheres in a multiphasic fashion including an initial burst phase, a slow linear release phase and a plateau phase. The release amount of TGF-beta1 was 37.4%, 50.7%, 61.3%, and 63.5% for 1, 3, 5, and 7 days respectively. At 21 days after cultivation, type II collagen immunohistochemical staining was performed. The mean percentage of positive cells for collagen type II in control group (32.7% +/ 10.4%) was significantly lower than that in the controlled TGF-beta1 release group (92.4% +/- 4.8%, P < 0.05). Both the proliferation rate and production of collagen type II in the transforming growth factor-beta1 microsphere incorporated scaffolds were significantly higher than those in the scaffolds without microspheres, indicating that the activity of TGF-beta1 was retained during microsphere fabrication and after growth factor release. CONCLUSION: Chitosan microspheres can serve as delivery vehicles for controlled release of TGF-beta1, and the released growth factor can augment chondrocytes proliferation and synthesis of extracellular matrix. Chitosan scaffolds incorporated with chitosan microspheres loaded with TGF-beta1 possess a promising potential to be applied for controlled cytokine delivery and cartilage tissue engineering. PMID- 17355822 TI - Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2. AB - BACKGROUND: Icariine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteoporosis. But the mechanism is unclear. The aim of the study was to research the effect of Icariine on the proliferation and differentiation of human osteoblasts. METHODS: Human osteoblasts were obtained by inducing human marrow mesenchymal stem cells (hMSCs) directionally and were cultured in the presence of various concentrations of Icariine. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was used to observe the effect of Icariine on cell proliferation. The activity of alkaline phosphatase (ALP) and the amount of calcified nodules were assayed to observe the effect on cell differentiation. The expression of bone morphogenetic protein 2 (BMP-2) mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Icariine (20 microg/ml) increased significantly the proliferation of human osteoblasts. And, Icariine (10 microg/ml and 20 microg/ml) increased the activity of ALP and the amount of calcified nodules of human osteoblasts significantly (P < 0.05). BMP-2 mRNA synthesis was elevated significantly in response to Icariine (20 microg/ml). CONCLUSIONS: Icariine has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblast cells in vitro, which may be mediated by increasing production of BMP-2 in osteoblasts. PMID- 17355823 TI - Torn discoid lateral meniscus treated with arthroscopic meniscectomy: observations in 62 knees. AB - BACKGROUND: Discoid lateral meniscus of the knee is common in Chinese population. There has been considerable debate about the best treatment for discoid lateral meniscus tears. The purpose of this study was to observe the effect of arthroscopic meniscectomy for the treatment of discoid lateral meniscus tears. METHODS: Between July 1999 and December 2004, arthroscopic meniscectomy was performed on 62 menisci of 57 patients with discoid lateral meniscus tears (52 unilateral, 5 bilateral). 41 menisci were "complete discoid meniscus", 21 "incomplete". According to the extent of the meniscus tears, partial meniscectomy was performed on 52 knees, total meniscectomy on 7 knees, and partial meniscectomy combined with meniscus suture on 3 knees through an arthroscope. After the operations, early rehabilitation training programs, including straight leg-raising and range-of-motion exercises, were carried out. 51 patients were followed up for 1 year 2 months to 6 years 5 months (mean, 3 years 3 months), 6 patients were lost. Lysholm-II scoring system was used to assess the function of the knee joints before the operation and during the follow-up. RESULTS: The operations on all the 62 knees were successful without complications. The patients could walk normally after completing the 2-week postoperation rehabilitation program. After 3 - 4 weeks they could lead a normal life and participate in a moderate amount of sports or other physical activities. The mean Lysholm-II score was 89 (60 - 100) during the follow-up, which was significantly higher than that before the operation (50, range 34 - 74; P < 0.01). 88% of the patients achieved excellent or good clinical results. CONCLUSIONS: Arthroscopic meniscectomy is an alternative for treatment of discoid lateral meniscus tears with minimal traumatic effects. It can achieve early mobilization and a low complication rate, as well as the preservation of the meniscus structure and functions to the largest extent. In combination with proper rehabilitation training, the operation can lead to good or excellent results. PMID- 17355824 TI - Treatment of cervical dislocation with locked facets. AB - BACKGROUND: Lower cervical dislocation with locked facets is common in cervical injury. The locked facets include unilateral and bilateral types. Different successful closed reduction rates has been achieved between unilateral and bilateral types by using rapid skull traction, which was commonly used to reduce the cervical dislocation. It is important to investigate a suitable management specific to patients with different types of cervical locked facets. METHODS: A total of 38 patients with cervical dislocation with locked facet due to cervical injury treated by rapid skull traction and operation from 1988 to 2005 were reviewed. Rapid skull traction was used in all the patients. Successful closed reduction rate was 88.0% in patients with bilateral cervical locked facets and that was 15.4% in those with unilateral cervical locked facets. These data were then statistically compared by Chi-square test. Patients who were reduced successfully underwent anterior cervical discectomy and fusion at the injured level, and those who failed in closed reduction received posterior open reduction and fixation. RESULTS: In this series, there was statistically significant difference (P < 0.05) in the rate of successful closed skull traction reduction between unilateral and bilateral locked facets dislocation. Unilateral cervical locked facets dislocation was not easily reduced by skull traction which was suitable for reduction of bilateral cervical locked facets dislocation. However, unilateral cervical locked facets dislocation can be reduced by posterior open reduction. CONCLUSIONS: Unilateral cervical locked facets dislocation should be treated immediately with posterior open reduction and instrumentation. Bilateral cervical locked facets dislocation can be reduced by rapid skull traction firstly and anterior cervical discectomy and interbody fusion later. PMID- 17355825 TI - Cerebrospinal fluid dynamics in Chiari malformation associated with syringomyelia. AB - BACKGROUND: About 50% - 70% of patients with Chiari malformation I (CMI) presented with syringomyelia (SM), which is supposed to be related to abnormal cerebrospinal fluid (CSF) flow around the foramen magnum. The aim of this study was to investigate the cerebrospinal fluid dynamics at levels of the aqueduct and upper cervical spine in patients with CMI associated with SM, and to discuss the possible mechanism of formation of SM. METHODS: From January to April 2004, we examined 10 adult patients with symptomatic CMI associated with SM and 10 healthy volunteers by phase-contrast MRI. CSF flow patterns were evaluated at seven regions of interest (ROI): the aqueduct and ventral and dorsal subarachnoid spaces of the spine at levels of the cerebellar tonsil, C2 - 3, and C5 - 6. The CSF flow waveforms were analyzed by measuring CSF circulation time, durations and maximum velocities of cranial- and caudal-directed flows, and the ratio between the two maximum velocities. Data were analyzed by t test using SPSS 11.5. RESULTS: We found no definite communication between the fourth ventricle and syringomyelia by MRI in the 10 patients. In both the groups, we observed cranial directed flow of CSF in the early cardiac systolic phase, which changed the direction from cranial to caudal from the middle systolic phase to the early diastolic phase, and then turned back in cranial direction in the late diastolic phase. The CSF flow disappeared at the dorsal ROI at the level of C2 - 3 in 3 patients and 1 volunteer, and at the level of C5 - 6 in 6 patients and 3 volunteers. The durations of CSF circulation at all the ROIs were significantly shorter in the patients than those in the healthy volunteers (P = 0.014 at the midbrain aqueduct, P = 0.019 at the inferior margin of the cerebellar tonsil, P = 0.014 at the level of C2 - 3, and P = 0.022 at the level of C5 - 6). No significant difference existed between the two groups in the initial point and duration of the caudal-directed CSF flow during a cardiac cycle at all the ROIs. The maximum velocities of both cranial- and caudal-directed CSF flows were significantly higher in the patients than those in the volunteers at the aqueduct (P = 0.018 and P = 0.007) and ventral ROI at the inferior margin of the cerebellar tonsil (P < 0.001 and P = 0.002), as so did the maximum velocities of the caudal-directed flow in the ventral and dorsal ROIs at the level of C2 - 3 (P = 0.004; P = 0.007). CONCLUSIONS: The direction of CSF flow changes in accordance with cardiac cycle. The syringomyelia in patients with CMI may be due to the decreased circulation time and abnormal dynamics of the CSF in the upper cervical segment. The decompression of the foramen magnum with dural plasty is an alternative for patients with CMI associated with SM. PMID- 17355826 TI - Management of intracranial invasive olfactory neuroblastoma. AB - BACKGROUND: Olfactory neuroblastoma (ONB) is a rare tumor that often arise from the nasal cavity. The aim of this study was to investigate the clinical characteristics and treatments of intracranial invasive ONB. METHODS: Between July 2001 and August 2005, 5 patients with intracranial invasive ONB were treated in our department. Their clinical features, radiological and pathological characteristics, and surgical treatments were analyzed. Among the 5 patients, 1 received transnasal biopsy, and 4 were operated through the transfrontal or extended bifrontal approaches to reconstruct the skull base. After the operation, all the patients received radiotherapy, and one received chemotherapy. They were followed up for 6 to 45 months. RESULTS: The ONB was resected totally in the 4 patients. In all the patients, nasal obstruction was alleviated without cerebrospinal fluid leakage. The visual acuity was improved in 3 patients, who had a decreased visual acuity before the operation. Two patients had metastasis into the lumbosacral spinal canal 6 and 8 months after the operation, one of them received a second operation and the other died. CONCLUSION: ONB has no specific symptoms. Intracranial ONB should be resected as far as possible, and treated by radiotherapy after the operation. PMID- 17355827 TI - Percutaneous microballoon compression for trigeminal neuralgia. AB - BACKGROUND: Percutaneous microballoon compression (PMC) for trigeminal neuralgia is an important therapeutic method. The aim of this study was to review the effects of PMC for trigeminal neuralgia in 276 patients. METHODS: From December 2000 to May 2003, 276 patients with trigeminal neuralgia were treated with PMC. The course of the disease ranged from 3 months to 38 years. Under the guidance of C-arm X-ray, 14# needle was placed into the foramen ovale using the classical Hakanson's technique. Fogarty balloon catheter was navigated into the Meckel's cave tenderly. A small amount of Omnipaque was slowly injected to inflate the balloon and compress the trigeminal ganglion for 3 to 10 minutes. RESULTS: A total of 290 PMC were performed on the 276 patients. Among them, 252 had immediate relief from pain. The patients were followed up for a mean of 18.7 months (range, 4 to 32), 14 of them had a recurrence. Of the 14 patients, 12 were re-operated with PMC, and the pain was all controlled successfully. CONCLUSIONS: PMC is an effective and technically simple method for trigeminal neuralgia. For older patients with trigeminal neuralgia, it may be the first choice. PMID- 17355828 TI - Inhibition effect of small interfering RNA of connective tissue growth factor on the expression of vascular endothelial growth factor and connective tissue growth factor in cultured human peritoneal mesothelial cells. AB - BACKGROUND: The peritoneum response to peritoneal dialysis can lead to fibrosis. The transforming growth factor beta1 (TGF-beta1) plays a key role in regulating tissue repair and remodelling after injury. Connective tissue growth factor (CTGF), a downstream mediator of TGF-beta1 inducing fibrosis, has been implicated in peritoneal fibrosis. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis that can hasten peritoneal fibrosis. In this study, we investigated the effect of small interfering RNA (siRNA) of CTGF by pRETRO-SUPER (PRS) retrovirus vector on the expression of CTGF and VEGF in human peritoneal mesothelial cells. METHODS: Retrovirus producing CTGF siRNA were constructed from the inverted oligonucleotides and transferred into packaging cell line PT67 with lipofectamine, and the virus supernatant was used to infect human peritoneal mesothelial cell (HPMC). The cells were divided into seven groups: low glucose DMEM, low glucose DMEM + TGF-beta1 5 ng/ml, low glucose DMEM + TGF-beta1 5 ng/ml + PRS-CTGF-siRNA(1-4) and low glucose DMEM + TGF-beta1 5 ng/ml + PRS. The expression of CTGF and VEGF were measured by semiquantitative RT-PCR and Western blot. RESULTS: Low levels of CTGF and VEGF were detected in confluent HPMCs. Following stimulation with TGF-beta1, the levels of CTGF and VEGF were significantly upregulated (P < 0.01). Introduction of PRS-CTGF-siRNA(1-4) resulted in the significant reduction of CTGF mRNA and protein, and VEGF mRNA (P < 0.01), especially in groups PRS-CTGF-siRNA1 and PRS-CTGF-siRNA4. The introduction of PRS void vector did not have these effects (P > 0.05). CONCLUSIONS: The expression of CTGF siRNA mediated by PRS retrovirus vector can effectively reduce the level of CTGF and VEGF induced by TGF-beta1 in cultured HPMCs. This study may provide potential therapeutic strategies to prevent the peritoneal fibrosis. PMID- 17355829 TI - Impact of overgrazing on the transmission of Echinococcus multilocularis in Tibetan pastoral communities of Sichuan Province, China. AB - BACKGROUND: Overgrazing was assumed to increase the population density of small mammals that are the intermediate hosts of Echinococcus multilocularis, the pathogen of alveolar echinococcosis in the Qinghai Tibet Plateau. This research tested the hypothesis that overgrazing might promote Echinococcus multilocularis transmission through increasing populations of small mammal, intermediate hosts in Tibetan pastoral communities. METHODS: Grazing practices, small mammal indices and dog Echinococcus multilocularis infection data were collected to analyze the relation between overgrazing and Echinococcus multilocularis transmission using nonparametric tests and multiple stepwise logistic regression. RESULTS: In the investigated area, raising livestock was a key industry. The communal pastures existed and the available forage was deficient for grazing. Open (common) pastures were overgrazed and had higher burrow density of small mammals compared with neighboring fenced (private) pastures; this high overgrazing pressure on the open pastures measured by neighboring fenced area led to higher burrow density of small mammals in open pastures. The median burrow density of small mammals in open pastures was independently associated with nearby canine Echinococcus multilocularis infection (P = 0.003, OR = 1.048). CONCLUSION: Overgrazing may promote the transmission of Echinococcus multilocularis through increasing the population density of small mammals. PMID- 17355830 TI - How should renin-angiotensin system blockade be applied in chronic kidney disease for optimal renal protection? PMID- 17355831 TI - Titanium mesh fusion device in the treatment of thoracolumbar burst fracture. PMID- 17355832 TI - Percutaneous drug-eluting stent implantation in dextrocardia: case report. PMID- 17355833 TI - Orthotopic liver transplantation with hepatopancreatoduodenectomy for hilar cholangiocarcinoma. PMID- 17355834 TI - Mucocele formation of cystic bile duct remnant after orthotopic liver transplantation. PMID- 17355835 TI - Solitary luteinized follicle cyst of pregnancy complicated with persistent postpartum vaginal bleeding: case report. PMID- 17355836 TI - Congenital short pancreas. PMID- 17355837 TI - Severe preeclampsia cured by heparin in a patient with twin-twin transfusion syndrome. PMID- 17355840 TI - [Work distribution between nurses and physicians]. PMID- 17355839 TI - Pathophysiologic mechanisms in REM sleep behavior disorder. AB - REM sleep behavior disorder (RBD) is a fascinating experiment in nature predicted by animal studies in 1964. A defining feature of REM sleep is active paralysis of all somatic musculature (sparing the diaphragm to permit respiration). RBD is characterized by the absence of REM atonia, permitting the appearance of dream enacting behaviors. These oneiric behaviors may be violent or injurious. RBD typically affects men over the age of 50 years. Longitudinal follow-up has shown that the majority of individuals with RBD will eventually develop additional signs and symptoms of a number of neurodegenerative disorders, most notably one of the synucleinopathies (Parkinson's disease, dementia with Lewy body disease, multiple system atrophy, or pure autonomic failure), often after a prolonged interval lasting more than 10 years. RBD is also a common manifestation of narcolepsy. RBD may be induced by medications, especially the tricyclic antidepressants and serotonin-specific reuptake inhibitors. In most cases, clonazepam is a highly effective treatment. PMID- 17355838 TI - Trigeminal autonomic cephalalgias: diagnosis and treatment. AB - The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders characterized by unilateral head pain that occurs in association with ipsilateral cranial autonomic features. The TACs include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and its close relative short lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). These syndromes cause patients considerable disability and certainly very significant suffering. They are distinguished by the frequency of attacks of pain, the length of the attacks, and very characteristic responses to medical therapy, such that the diagnosis can usually be made clinically, which is important because it completely dictates therapy. The management of TACs can be very rewarding for physicians and highly beneficial to patients. PMID- 17355841 TI - [Anti-TNF-alpha antibody treatment of patients with active ulcerative colitis]. AB - Recently published studies have demonstrated that infliximab is effective not only in Crohn's disease, but also in ulcerative colitis. The present article reviews current treatment options for severe ulcerative colitis as well as available data on the effect of infliximab in the treatment of this disease. The article discusses the possible future role of infliximab in the treatment of ulcerative colitis. PMID- 17355842 TI - [TNF-alpha antibody treatment and remission induction in ulcerative colitis: a review of a Cochrane review]. PMID- 17355843 TI - [Spinal and epidural anesthesia]. PMID- 17355844 TI - [Medical treatment of chemotherapy-induced nausea and vomiting]. AB - Patients consider nausea and vomiting among the worst side effects of chemotherapy. This paper reviews the development of antiemetics during the past 12 years, focusing on the neurokinin (NK)1-receptor antagonist, aprepitant, and the new 5-HT3-receptor antagonist palonosetron. Evidence-based recommendations for prophylaxis of chemotherapy-induced nausea and vomiting are given. Antiemetics are effective in prevention of vomiting, but less effective against nausea. Therefore studies with potential new antiemetics, such as olanzapine and ghrelin are awaited with suspense. PMID- 17355845 TI - [Changes in personnel performing gastroenterologic tests, with special emphasis on endoscopy]. AB - In the gastroenterologic field, there has been an increasing need for endoscopy. With future screening programs, the number of endoscopies performed will further increase. In Denmark endoscopies are performed primarily by doctors, but soon the number of endoscopies done will exceed the capacities of the doctors who perform them. International experience with nurse endoscopists has shown good results, with safety, sensitivity and specificity comparable to doctors'. This paper discusses the possibilities for nurses' performing endoscopy. PMID- 17355846 TI - [Fast-tracking admission from emergency room to orthopaedic ward in hip fracture patients]. AB - INTRODUCTION: The traditional admission protocol for hip fracture patients often results in long waiting hours in the A&E. The aim of this study was to investigate the effect of an optimised admission protocol on the time spent in the A&E in an already established multimodal rehabilitation program. MATERIALS: Descriptive, prospective intervention study in two groups of 150 hip fracture patients admitted before and after the implementation of an optimised admission protocol, which included nurse requested x-ray and opioid-free analgesic. RESULTS: The median waiting time in the control group was 251 min (83-632 min.) compared to 185 min (58-522 min, p < 0,001)) in the intervention group. The median waiting time for operation was 18-19 hours in both groups. CONCLUSION: An optimised admission protocol, including nurse requested X-ray for hip fracture patients, led to a reduction in the time spent in the A&E. PMID- 17355847 TI - [Endoscopic vein harvest in coronary bypass]. AB - INTRODUCTION: Saphenous vein is the most commonly used conduit in coronary revascularization. Traditional open vein harvest often leads to impaired wound healing and postoperative infection. In the Department of Cardiothoracic Surgery, University Hospital of Copenhagen, we have introduced endoscopic vein harvest and this study describes our first experiences. MATERIALS AND METHODS: From January to October 2004 the saphenous vein was harvested endoscopically in 38 patients. We used the disposable Guidant VasoView EVH System to mobilize the vein and divide the side branches through a 2-3 cm incision. Data are analyzed retrospectively. RESULTS: None of the patients had postoperative complications with their donor site. 68% of the harvested veins were of good quality and only 8% were of a poor quality. The inferior quality of these veins was anatomical and not due to technical problems. CONCLUSION: Large randomized trials including two metaanalyses show that endoscopic harvesting of the saphenous vein reduces infection and wound healing problems in patients undergoing cardiac surgery without reducing the quality of the vein. Our data confirm the hypothesis that the method can be introduced with good results and reasonable learning curves. PMID- 17355848 TI - [Greenhouse gardeners and sickness absence. A questionnaire study among greenhouse gardeners in Aarhus region]. AB - INTRODUCTION: The aim of the study was to examine sickness absence and risk factors for sickness absence in a population of greenhouse gardeners in the county of Arhus. METHODS: The study was cross sectional and based on data from questionnaires sent to all employees and greenhouse gardens in the county. RESULTS: Greenhouse gardeners had an average of four days of sickness absence a year. Self-rated health was poorer than average of the Danish population in general. Female gender, age below 40 years, troublesome relationships to family and friends, "poor" physical working environment and job insecurity were all predictors for increased risk of sickness absence lasting more than two weeks a year. DISCUSSIONS: Sickness absence was low compared to the average of the Danish labour market. Considering poorer self-rated health and frequent occurrence of some of the above-mentioned predictors for increased risk of sickness absence- female gender, age below 40 years and for women, high exposure to "poor" physical working environment--an average sickness absence of only four days was a puzzle. The data from the study were not sufficient to explain this paradox. It might be due to compensating factors at work or at a personal level. It might be due to information bias, as sickness absence could be underestimated, but agreement between reported sickness absence from employees and greenhouse gardens diminished that probability. It might have been a consequence of selection bias, the "healthy workers'" effect. Employees with considerable sickness absence might have been dismissed for long-term absence or might have quit the job because they were not able to cope with it. PMID- 17355849 TI - [Risk of hospitalisation due to foodborne bacterial gastroenteritis--secondary publication]. AB - In a matched cohort study we estimate the risk of hospitalisation due to gastroenteritis, complications and sequelae after infections with zoonotic Salmonella, Campylobacter spp., Yersinia enterocolitica, E. coli and Shigella infections. Out of 52,783 patients, 7,524 (14.4%) were hospitalized with gastroenteritis, 647 (1.2%) with complications and 865 (1.7%) with long-term sequelae. In Denmark in 2005 there were 6,010 registered episodes of infections with bacteria that are usually foodborne, contributing to an estimated 6,267 days of hospitalisation. PMID- 17355850 TI - [Do wine drinkers eat healthier than beer drinkers? A cross sectional study of 3(1/2) million purchases in Danish supermarkets--secondary publication]. AB - In a cross sectional study based on information on the number, type of item and total charge of 3(1/2) million transactions over a period of 6 months in various supermarkets in Denmark we examined whether people who buy wine also buy healthier food items than those who buy beer. We found that wine buyers bought more olives, fruit and vegetables, poultry, cocking oil and low fat cheese, milk and meat than beer buyers who bought more ready cooked meals, sugar, cold cuts, chips, pork, butter or margarine, sausages, lamb and soft drinks than wine buyers. PMID- 17355851 TI - [Tuberculosis in the ankle of a Danish-born man]. AB - Since the 1990s, we have witnessed an increase in the incidence of extrapulmonary tuberculosis in Denmark among foreigners as well as Danes. This case history describes a Danish man with an infection in his right ankle colonised with Mycobacterium tuberculosis. The man was treated with surgical revision and antituberculous drugs, and arthrodesis of the right ankle and heel was performed. This case is described to draw attention to the possibility of extrapulmonary tuberculosis when presented with infections in bones and joints. PMID- 17355852 TI - [Prenatal diagnosis of congenital insulin-resistant diabetes (Donohue's syndrome)]. AB - A consanguineous Turkish couple was expecting their third child. Two years earlier their second child had died from a severe form of insulin-resistant diabetes causing Donohue's syndrome. A novel mutation (V335) in the insulin receptor gene was found to be disrupting the structure and function of the receptor. The parents, as well as their first child, were asymptomatic, heterozygous carriers. The family received genetic counselling, and chorion villus sampling was performed early in pregnancy. Genotyping showed that the child in utero was heterozygous for the mutation. Subsequently the mother gave birth to a healthy boy. PMID- 17355853 TI - Ophthalmic management of facial nerve palsy: a review. AB - Facial nerve palsy affects individuals of all ages, races, and sexes. Psychological and functional implications of the paralysis present a devastating management problem to those afflicted, as well as the carriers. Since Sir Charles Bell's original description of facial palsy in 1821, our understanding and treatment options have expanded. It is essential that a multidisciplinary approach, encompassing ophthalmologists; Ear, Nose, and Throat surgeons; plastic surgeons; and psychologists work closely to optimize patient management in a staged approach. Although the etiology remains unknown, strong histological, cerebral spinal fluid, and radiological evidence suggests a possible association with herpes simplex virus in idiopathic facial nerve palsy (Bell's palsy). The use of steroids has been suggested as a means of limiting facial nerve damage in the acute phase. Unfortunately, no single randomized control trial has achieved an unquestionable benefit with the use of oral steroid therapy and thus remains controversial. In the acute phase, ophthalmologists play a pivotal role in preventing irreversible blindness from corneal exposure. This may be successfully achieved by using intensive lubrication, medical therapy (botulinum toxin), or surgery (upper lid weighting or tarsorraphy). Once the cornea is adequately protected and recovery deemed unlikely, longer term planning for eyelid and facial reanimation may take place in an individualized manner. Onset is sudden and management potentially lengthy. Physician empathy, knowledge, and experience are essential in averting long-term lifestyle and psychological discomfort for patients. PMID- 17355854 TI - Porous orbital implants in enucleation: a systematic review. AB - Orbital implants have been used for cosmesis following surgical removal of the eyeball, or enucleation, for over a century. Implant design has progressed significantly in recent years with the use of porous devices, with the theoretical advantages of reduced complications and improved cosmesis. However, in some cases the theoretical benefits have not fully translated into clinical results. In this article the use of orbital implants in enucleation, with a particular focus on the newer porous biomaterials that have gained prominence over the last 15 years, is reviewed. Specific factors identified as affecting the performance of porous orbital implants include the material used, pore size, and morphology. Mechanical factors have received little consideration in the past and may form a basis for the use of higher compliance porous materials in the future. Of the porous materials in use, current clinical evidence is not sufficient to suggest either that porous implants are superior to non-porous implants, or that one material is more suited to the application than another. Future developments in this field require randomized controlled clinical trials with extensive follow up as complications may not become evident until over 5 years post-implantation. PMID- 17355855 TI - Staging functional damage in glaucoma: review of different classification methods. AB - Classification of glaucomatous visual field defects for different severity levels is important. The reasons for this are numerous, and include: to distinguish between healthy and diseased individuals, to have homogeneous grouping criteria when perimetry is used to define the severity of glaucoma, to adjust therapy on the basis of disease severity, to describe visual field conditions in a short and simple format, to monitor the progression of the disease, and to provide a common language for both clinical and research purposes. Many severity classification methods have been proposed, although none have had widespread use in clinical practice. Other methods, like the cumulative defect curve (Bebie curve), can be used to distinguish the type of visual field loss as diffuse, localized, or mixed. This article provides a review of the main classification methods that have been proposed in the past 40 years. PMID- 17355857 TI - Electrically assisted ocular gene therapy. AB - Electrotransfer and iontophoresis are being developed as innovative non-viral gene delivery systems for the treatment of eye diseases. These two techniques rely on the use of electric current to allow for higher transfection yield of various ocular cell types in vivo. Short pulses of relatively high-intensity electric fields are used for electrotransfer delivery, whereas the iontophoresis technique is based on the application of low voltage electric current. The basic principles of these techniques and their potential therapeutic application for diseases of the anterior and posterior segments of the eye are reviewed. Iontophoresis has been found most efficient for the delivery of small nucleic acid fragments such as antisense oligonucleotides, siRNA, or ribozymes. Electrotransfer, on the other hand, is being developed for the delivery of oligonucleotides or custom designed plasmids. The wide range of strategies already validated and the potential for targeting specific types of cells confirm the promising early observations made using electrotransfer and iontophoresis. These two nonviral delivery systems are safe and can be used efficiently for targeted gene delivery to ocular tissues in vivo. At the present, their application for the treatment of ocular human diseases is nearing its final stages of adaptation and practical implementation at the bedside. PMID- 17355858 TI - Migraine and anisocoria. AB - A 42-year-old woman presents with headache and anisocoria. Gonioscopy suggested narrow angles. Ultrasound biomicroscopy confirmed the diagnosis. The patient underwent bilateral peripheral iridotomies with resolution of her symptoms. The differential diagnosis of headache and anisocoria are reviewed. Plateau iris syndrome and subacute angle closure are discussed. PMID- 17355859 TI - Metastasis to the eye and orbit from renal cell carcinoma--a report of three cases and review of literature. AB - We report three cases of renal cell carcinoma metastatic to the eye and orbit and review the relevant literature. The case reports of a 67-year-old man, a 58-year old man, and a 23-year-old woman with metastatic renal cell carcinoma are described. The iris mass occurred in a 67-year-old man, a known case of renal cell carcinoma. Whereas the orbital metastasis in the 58-year-old man was the initial presenting sign in a hitherto undiagnosed patient, the orbital metastasis in the 23-year-old female patient was detected following nephrectomy for renal cell carcinoma. Renal cell carcinoma metastasizing to the eye and orbit are very rare, with only 68 cases reported previously. In patients presenting with atypical orbital or ocular masses, the possibility of renal cell carcinoma metastasis should be considered, especially if there is a history of previous renal disorder. Incisional biopsy with histopathological evaluation may be an important means to diagnose this condition and facilitate appropriate therapy. PMID- 17355860 TI - Secretion superfamily ATPases swing big. PMID- 17355856 TI - Obesity and eye diseases. AB - The prevalence of obesity has reached epidemic proportions in many countries. Although its impact on overall health is well documented, less is known about the ocular manifestations of obesity. Among different eye diseases, obesity has been linked with age-related cataract, glaucoma, age-related maculopathy, and diabetic retinopathy. Numerous population-based and prospective studies support an association between obesity and risk of age-related cataract. However, the nature and strength of these associations, particularly with the different cataract subtypes, remains to be determined. There is strong evidence that obesity is associated with elevated intraocular pressure, but there is no convincing data to support a more direct association between obesity and glaucomatous optic neuropathy. Studies to date have not found a consistent pattern of association between obesity and risk of age-related maculopathy or diabetic retinopathy. Thus, although obesity may be a risk factor for many ocular conditions, the present literature is inadequate to establish any convincing associations. Furthermore, whether weight loss reduces the risk of eye diseases remains unresolved. Because of the potential public health impact of obesity, there is a greater need to understand its ocular effects. PMID- 17355861 TI - The THI-box riboswitch, or how RNA binds thiamin pyrophosphate. AB - Riboswitches are genetic control elements present mainly in the 5' untranslated regions of messenger RNAs that, upon binding of a small metabolite (like some vitamins, amino acids, and nucleobases), undergo conformational changes, affecting the expression of downstream genes. Structural studies of riboswitches are important for understanding how they recognize their ligands with high specificity and affinity. The thiamin pyrophosphate binding riboswitch (THI- box) is widely distributed in the three kingdoms of life and is involved in very distinct modes of gene regulation. Three recent THI-box structural analyses revealed how polyanionic RNA is able to bind a molecule with a negatively charged pyrophosphate group like thiamin pyrophosphate (TPP) and how it can discriminate between TPP and monophosphorylated analog molecules. These studies give insight into the genetic regulatory mechanisms in which the THI-box is involved. PMID- 17355862 TI - Glycoprotein structural genomics: solving the glycosylation problem. AB - Glycoproteins present special problems for structural genomic analysis because they often require glycosylation in order to fold correctly, whereas their chemical and conformational heterogeneity generally inhibits crystallization. We show that the "glycosylation problem" can be solved by expressing glycoproteins transiently in mammalian cells in the presence of the N-glycosylation processing inhibitors, kifunensine or swainsonine. This allows the correct folding of the glycoproteins, but leaves them sensitive to enzymes, such as endoglycosidase H, that reduce the N-glycans to single residues, enhancing crystallization. Since the scalability of transient mammalian expression is now comparable to that of bacterial systems, this approach should relieve one of the major bottlenecks in structural genomic analysis. PMID- 17355863 TI - Multiprotein expression strategy for structural biology of eukaryotic complexes. AB - The concept of the cell as a collection of multisubunit protein machines is emerging as a cornerstone of modern biology, and molecular-level study of these machines in most cases will require recombinant production. Here, we present and validate a strategy to rapidly produce, permutate, and posttranslationally modify large, eukaryotic multiprotein complexes by using DNA recombination in a process that is fully automatable. Parallel production of 12 protein complex variants within a period of weeks resulted in specimens of sufficient quantity and homogeneity for structural biology applications. PMID- 17355864 TI - Structural roles of monovalent cations in the HDV ribozyme. AB - The hepatitis delta virus (HDV) ribozyme catalyzes viral RNA self-cleavage through general acid-base chemistry in which an active-site cytidine and at least one metal ion are involved. Monovalent metal ions support slow catalysis and were proposed to substitute for structural, but not catalytic, divalent metal ions in the RNA. To investigate the role of monovalent cations in ribozyme structure and function, we determined the crystal structure of the precursor HDV ribozyme in the presence of thallium ions (Tl(+)). Two Tl(+) ions can occupy a previously observed divalent metal ion hexahydrate-binding site located near the scissile phosphate, but are easily competed away by cobalt hexammine, a magnesium hexahydrate mimic and potent reaction inhibitor. Intriguingly, a third Tl(+) ion forms direct inner-sphere contacts with the ribose 2'-OH nucleophile and the pro S(p) scissile phosphate oxygen. We discuss possible structural and catalytic implications of monovalent cation binding for the HDV ribozyme mechanism. PMID- 17355865 TI - A snapshot of the 30S ribosomal subunit capturing mRNA via the Shine-Dalgarno interaction. AB - In the initiation phase of bacterial translation, the 30S ribosomal subunit captures mRNA in preparation for binding with initiator tRNA. The purine-rich Shine-Dalgarno (SD) sequence, in the 5' untranslated region of the mRNA, anchors the 30S subunit near the start codon, via base pairing with an anti-SD (aSD) sequence at the 3' terminus of 16S rRNA. Here, we present the 3.3 A crystal structure of the Thermus thermophilus 30S subunit bound with an mRNA mimic. The duplex formed by the SD and aSD sequences is snugly docked in a "chamber" between the head and platform domains, demonstrating how the 30S subunit captures and stabilizes the otherwise labile SD helix. This location of the SD helix is suitable for the placement of the start codon AUG in the immediate vicinity of the mRNA channel, in agreement with reported crosslinks between the second position of the start codon and G1530 of 16S rRNA. PMID- 17355866 TI - c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty. AB - The cancer drug imatinib inhibits the tyrosine kinases c-Abl, c-Kit, and the PDGF receptor. Imatinib is less effective against c-Src, which is difficult to understand because residues interacting with imatinib in crystal structures of Abl and c-Kit are conserved in c-Src. The crystal structure of the c-Src kinase domain in complex with imatinib closely resembles that of Abl*imatinib and c Kit*imatinib, and differs significantly from the inactive "Src/CDK" conformation of the Src family kinases. Attempts to increase the affinity of c-Src for imatinib by swapping residues with the corresponding residues in Abl have not been successful, suggesting that the thermodynamic penalty for adoption of the imatinib-binding conformation by c-Src is distributed over a broad region of the structure. Two mutations that are expected to destabilize the inactive Src/CDK conformation increase drug sensitivity 15-fold, suggesting that the free-energy balance between different inactive states is a key to imatinib binding. PMID- 17355867 TI - Substrate recognition reduces side-chain flexibility for conserved hydrophobic residues in human Pin1. AB - Pin1 is a peptidyl-prolyl isomerase consisting of a WW domain and a catalytic isomerase (PPIase) domain connected by a flexible linker. Pin1 recognizes phospho Ser/Thr-Pro motifs in cell-signaling proteins, and is both a cancer and an Alzheimer's disease target. Here, we provide novel insight into the functional motions underlying Pin1 substrate interaction using nuclear magnetic resonance deuterium ((2)D) and carbon ((13)C) spin relaxation. Specifically, we compare Pin1 side-chain motions in the presence and absence of a known phosphopeptide substrate derived from the mitotic phosphatase Cdc25. Substrate interaction alters Pin1 side-chain motions on both the microsecond-millisecond (mus-ms) and picosecond-nanosecond (ps-ns) timescales. Alterations include loss of ps-ns flexibility along an internal conduit of hydrophobic residues connecting the catalytic site with the interdomain interface. These residues are conserved among Pin1 homologs; hence, their dynamics are likely important for the Pin1 mechanism. PMID- 17355868 TI - Modular structure of the full-length DNA gyrase B subunit revealed by small-angle X-ray scattering. AB - DNA gyrase, the only topoisomerase able to introduce negative supercoils into DNA, is essential for bacterial transcription and replication; absent from humans, it is a successful target for antibacterials. From biophysical experiments in solution, we report a structural model at approximately 12-15 A resolution of the full-length B subunit (GyrB). Analytical ultracentrifugation shows that GyrB is mainly a nonglobular monomer. Ab initio modeling of small angle X-ray scattering data for GyrB consistently yields a "tadpole"-like envelope. It allows us to propose an organization of GyrB into three domains ATPase, Toprim, and Tail-based on their crystallographic and modeled structures. Our study reveals the modular organization of GyrB and points out its potential flexibility, needed during the gyrase catalytic cycle. It provides important insights into the supercoiling mechanism by gyrase and suggests new lines of research. PMID- 17355869 TI - Similar binding sites and different partners: implications to shared proteins in cellular pathways. AB - We studied a data set of structurally similar interfaces that bind to proteins with different binding-site structures and different functions. Our multipartner protein interface clusters enable us to address questions like: What makes a given site bind different proteins? How similar/different are the interactions? And, what drives the apparently less-specific association? We find that proteins with common binding-site motifs preferentially use conserved interactions at similar interface locations, despite the different partners. Helices are major vehicles for binding different partners, allowing alternate ways to achieve favorable association. The binding sites are characterized by imperfect packing, planar architectures, bridging water molecules, and, on average, smaller size. Interestingly, analysis of the connectivity of these proteins illustrates that they have more interactions with other proteins. These findings are important in predicting "date hubs," if we assume that "date hubs" are shared proteins with binding sites capable of transient binding to multipartners, linking higher-order networks. PMID- 17355870 TI - Crystal structure of a TOG domain: conserved features of XMAP215/Dis1-family TOG domains and implications for tubulin binding. AB - Members of the XMAP215/Dis1 family of microtubule-associated proteins (MAPs) are essential for microtubule growth. MAPs in this family contain several 250 residue repeats, called TOG domains, which are thought to bind tubulin dimers and promote microtubule polymerization. We have determined the crystal structure of a single TOG domain from the Caenorhabditis elegans homolog, Zyg9, to 1.9 A resolution, and from it we describe a structural blueprint for TOG domains. These domains are flat, paddle-like structures, composed of six HEAT-repeat elements stacked side by side. The two wide faces of the paddle contain the HEAT-repeat helices, and the two narrow faces, the intra- and inter-HEAT repeat turns. Solvent-exposed residues in the intrarepeat turns are conserved, both within a particular protein and across the XMAP215/Dis1 family. Mutation of some of these residues in the TOG1 domain from the budding yeast homolog, Stu2p, shows that this face indeed participates in the tubulin contact. PMID- 17355872 TI - Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin. AB - Sirtuins are NAD(+)-dependent protein deacetylases and are emerging as molecular targets for the development of pharmaceuticals to treat human metabolic and neurological diseases and cancer. To date, several sirtuin inhibitors and activators have been identified, but the structural mechanisms of how these compounds modulate sirtuin activity have not yet been determined. We identified suramin as a compound that binds to human SIRT5 and showed that it inhibits SIRT5 NAD(+)-dependent deacetylase activity with an IC(50) value of 22 microM. To provide insights into how sirtuin function is altered by inhibitors, we determined two crystal structures of SIRT5, one in complex with ADP-ribose, the other bound to suramin. Our structural studies provide a view of a synthetic inhibitory compound in a sirtuin active site revealing that suramin binds into the NAD(+), the product, and the substrate-binding site. Finally, our structures may enable the rational design of more potent inhibitors. PMID- 17355871 TI - Crystal structures of the pilus retraction motor PilT suggest large domain movements and subunit cooperation drive motility. AB - PilT is a hexameric ATPase required for bacterial type IV pilus retraction and surface motility. Crystal structures of ADP- and ATP-bound Aquifex aeolicus PilT at 2.8 and 3.2 A resolution show N-terminal PAS-like and C-terminal RecA-like ATPase domains followed by a set of short C-terminal helices. The hexamer is formed by extensive polar subunit interactions between the ATPase core of one monomer and the N-terminal domain of the next. An additional structure captures a nonsymmetric PilT hexamer in which approach of invariant arginines from two subunits to the bound nucleotide forms an enzymatically competent active site. A panel of pilT mutations highlights the importance of the arginines, the PAS-like domain, the polar subunit interface, and the C-terminal helices for retraction. We present a model for ATP binding leading to dramatic PilT domain motions, engagement of the arginine wire, and subunit communication in this hexameric motor. Our conclusions apply to the entire type II/IV secretion ATPase family. PMID- 17355873 TI - Distribution of reaction products in phospholipase A2 hydrolysis. AB - We have monitored the composition of supported phospholipid bilayers during phospholipase A(2) hydrolysis using specular neutron reflection and ellipsometry. Porcine pancreatic PLA(2) shows a long lag phase of several hours during which the enzyme binds to the bilayer surface, but only 5+/-3% of the lipids react before the onset of rapid hydrolysis. The amount of PLA(2), which resides in a 21+/-1 A thick layer at the water-bilayer interface, as well as its depth of penetration into the membrane, increase during the lag phase, the length of which is also proportional to the enzyme concentration. Hydrolysis of a single-chain deuterium labelled d(31)-POPC reveals for the first time that there is a significant asymmetry in the distribution of the reaction products between the membrane and the aqueous environment. The lyso-lipid leaves the membrane while the number of PLA(2) molecules bound to the interface increases with increasing fatty acid content. These results constitute the first direct measurement of the membrane structure and composition, including the location and amount of the enzyme during hydrolysis. These are discussed in terms of a model of fatty-acid mediated activation of PLA(2). PMID- 17355874 TI - Midbrain modulation of the cardiac baroreflex involves excitation of lateral parabrachial neurons in the rat. AB - Activation of the dorsal periaqueductal gray (PAG) evokes defense-like behavior including a marked increase in sympathetic drive and resetting of baroreflex function. The goal of this study was to investigate the role of the lateral parabrachial nucleus (LPBN) in mediating dorsal PAG modulation of the arterial baroreflex. Reflex responses were elicited by electrical stimulation of the aortic depressor nerve (ADN) at 5 Hz or 15 Hz in urethane anesthetized rats (n=18). Electrical stimulation of the dorsal PAG at 10 Hz did not alter baseline mean arterial pressure (MAP) but did significantly attenuate baroreflex control of heart rate (HR) evoked by low frequency ADN stimulation. Alternatively, 40 Hz dorsal PAG stimulation increased baseline MAP (43+/-3 mm Hg) and HR (33+/-3 bpm) and attenuated baroreflex control of HR at both ADN stimulation frequencies. Reflex control of MAP was generally unchanged by dorsal PAG stimulation. Bilateral inhibition of neurons in LPBN area (n=6) with muscimol (0.45 nmol per side) reduced dorsal PAG-evoked increases in MAP and HR by 50+/-4% and 95+/-4%, respectively, and significantly reduced, but did not completely eliminate dorsal PAG attenuation of the cardiac baroreflex. Bilateral blockade of glutamate receptors in the LPBN area (n=6) with kynurenic acid (1.8 nmol) had a similar effect on dorsal PAG-evoked increases in MAP, HR and cardiac baroreflex function. Reflex control of MAP was unchanged with either treatment. These findings suggest that the LPBN area is one of several brainstem regions involved in descending modulation of the cardiac baroreflex function during defensive behavior. PMID- 17355875 TI - Calcineurin-independent inhibition of the delayed rectifier K+ current by the immunosuppressant FK506 in rat hippocampal neurons. AB - The immunosuppressant drug FK506 was found to be a potent neuroprotective agent in animal models of brain ischemia. However, the mechanisms underlying the action remain to be elucidated. The delayed rectifier K(+) channel has been implicated in ischemic injury and neuronal death in the brain. The aim of the present study is to investigate whether the neuroprotective action of FK506 results from blocking the K(+) channel. In acutely dissociated CA1 pyramidal neurons of rat hippocampus, superfusion of FK506 (0.01-100 microM) selectively inhibited the delayed rectifier K(+) current (I(K)) with an IC(50) value of 13.2+/-4.9 microM. The inhibition of I(K) by FK506 (10 microM) had a rapid onset, and then gradually reached a steady-state level. The inhibition was voltage-dependent, became more potent when the currents were elicited by strong depolarization. Moreover, FK506 (10 microM) caused marked negative shifts of the steady-state activation and inactivation curves of I(K), and accelerated its recovery from inactivation. Intracellular dialysis of FK506 (30 microM) was ineffective. The inhibition of I(K) by FK506 (10 microM) persisted under the low-Ca(2+) conditions that blocked the basal activity of protein phosphatase 2B (calcineurin). Rapamycin did not antagonize FK506 but mimicked it. Cyclosporin A inhibited I(K) only at 30 and 100 microM. Taken together, the results suggest that FK506 exert a direct inhibition on the delayed rectifier K(+) channel without involvement of calcineurin. PMID- 17355876 TI - Acute activation of CB1 cannabinoid receptors transiently decreases PSA-NCAM expression in the dentate gyrus of the rat hippocampus. AB - Recent evidence indicates that the polysialylated neural cell adhesion molecule (PSA-NCAM) is involved in hippocampal plasticity. On the other hand, CB1 receptor activation is known to disturb some hippocampal processes involving plastic changes, such as learning and memory. Therefore, the present study investigated the effect of HU-210, a CB1 receptor agonist, on the expression of PSA-NCAM protein in the dentate gyrus (DG) and CA3 region of the rat hippocampus. It was found that at a dose of 0.1 mg/kg i.p. of HU-210, the number of PSA-NCAM immunoreactive (IR) cells in the DG declined in a time-dependent manner. The decrease in PSA-NCAM expression was observed at 1 and 2 days (ca. 21% and 30%, respectively), but not after 4 h and 4 days following HU-210 administration. However, HU-210 treatment did not change the length density of PSA-NCAM immunopositive processes in CA3 mossy fibers at all the time points measured. The effect observed in the DG on day 2 was blocked by AM-251 (1 mg/kg, i.p.), a CB1 receptor antagonist, given 30 min before HU-210. Neither the number of Ki-67 (IR) cells (a marker of proliferation) nor the number of doublecortin-IR cells (a marker of immature neurons) was affected by HU-210 (0.1 mg/kg, i.p.) treatment at any of the time points. An analysis of co-localization of CB1 receptor protein with PSA-NCAM protein revealed that both proteins were not present in the same population of neurons in the subgranular layer of the DG. The observed changes in PSA-NCAM expression were not related to the reduction of proliferation or differentiation of newly born cells, but were possible due to alternations in the synaptic activity in the DG. However, such alteration in the PSA-NCAM expression may change the timing of the functional maturation of newly born neurons. Moreover, the above finding suggests that acute activation of CB1 receptors may result in the stiffening of the hippocampal structure and susceptibility to plastic changes and may lead to functional impairment governed by alterations in the hippocampal structure. PMID- 17355877 TI - Clinical significance of ELISA positive and immunofluorescence negative anti dsDNA antibody. AB - BACKGROUND: Positivity for anti-dsDNA antibody is a diagnostic criterion of systemic lupus erythematosus (SLE). In the present study, the significance of ELISA positive and Crithidia luciliae immunofluorescence test (CLIFT) negative anti-dsDNA sera was evaluated. METHODS: There were 371 consecutive serum samples submitted to for anti-dsDNA testing that were assayed using anti-dsDNA ELISA and CLIFT. Sera showing discrepant results were collected and then examined using 3 commercial anti-dsDNA and anti-ssDNA ELISA kits and by Farr assay. Medical records were reviewed for those patients who were ELISA positive and CLIFT negative for anti-dsDNA. RESULTS: Fifty-two patients of 100 anti-dsDNA ELISA positive patients were negative by CLIFT. For ELISA positive and CLIFT negative sera, Farr assays showed the highest positive rate (72.7%) for the 4 different anti-dsDNA assays (3 commercial kits and the Farr assay). Nearly 80% of 44 ELISA positive and CLIFT negative patients met >or=3 of the SLE classification criteria (excluding the anti-dsDNA criterion). CONCLUSION: Some anti-dsDNA ELISA kits have diagnostic efficiencies that are similar to that of the Farr assay. Moreover, the study identifies a group of patients that are ELISA positive but CLIFT negative for anti-dsDNA, and indicates that the majority of these patients have clinically relevant SLE. PMID- 17355878 TI - Increased apoptosis of parasympathetic but not enteric neurons in mice lacking GFRalpha2. AB - Enteric neurons, unlike sympathetic and sensory neurons that require target derived neurotrophins for survival, do not undergo classical caspase-3-mediated programmed cell death (PCD) during normal development. Whether parasympathetic neurons in the pancreas, which originate from a subpopulation of enteric nervous system (ENS) precursors, or other parasympathetic neurons undergo PCD during normal mammalian development is unknown. In GFRalpha2-deficient mice, many submandibular and intrapancreatic parasympathetic neurons are missing but whether this is due to increased neuronal death is unclear. Here we show that activated caspase-3 and PGP9.5 doubly positive neurons are present in wild-type mouse pancreas between embryonic day E15 and birth. Thus, in contrast to ENS neurons, intrapancreatic neurons undergo PCD via apoptosis during normal development. We also show that, in GFRalpha2-deficient mice, most intrapancreatic neurons are lost during this late fetal period, which coincides with a period of increased apoptosis of the neurons. Since the percentage of BrdU and Phox2b doubly positive cells in the fetal pancreas and the number of intrapancreatic neurons at E15 were similar between the genotypes, impaired precursor proliferation and migration are unlikely to contribute to the loss of intrapancreatic neurons in GFRalpha2-KO mice. Caspase-3-positive neurons were also found in GFRalpha2-deficient submandibular ganglia around birth, suggesting that parasympathetic neurons depend on limited supply of (presumably target-derived neurturin) signaling via GFRalpha2 for survival. PMID- 17355879 TI - Cord blood and myocardial infarction: an uncertain wedding. PMID- 17355881 TI - The pH-dependence of the Escherichia coli RNase HII-catalysed reaction suggests that an active site carboxylate group participates directly in catalysis. AB - RNase HII specifically catalyses the hydrolysis of phosphate diester linkages contained within the RNA portion of DNA/RNA hybrids. The catalytic parameters of the enzyme derived from Escherichia coli BL21 have been measured using 5' fluorescent oligodeoxynucleotide substrates containing embedded ribonucleotides. The products of the reaction and the chemistry of phosphate diester hydrolysis were assigned unequivocally using mass spectrometry. The pH-dependence of the catalytic parameters was measured under conditions of optimal magnesium ion concentration. The logarithm of the turnover number of the enzyme increases steeply with pH until a pH-independent region is reached close to neutrality. The slope of the pH-dependent region is 2, indicating that the catalytically proficient form of RNase HII is di-anionic. The pH-dependence of log 1/K(M) is a sigmoidal curve reaching a maximal value at higher pH, suggesting deprotonation of a residue stabilises substrate binding. Possible mechanisms for the RNase HII catalysed reaction consistent with the pH-dependent behaviour of the enzyme are discussed. The active sites of RNase H enzymes contain a cluster of four strictly conserved carboxylate groups. Together, the data suggest a requirement for ionisation of an active site carboxylic acid for metal ion binding or correct positioning of metal ion(s) in the enzyme-substrate complex and a role for a second active site carboxylate in general base catalysis. PMID- 17355880 TI - Impact of pro segments on the folding and function of human neutrophil alpha defensins. AB - Human neutrophil alpha-defensins (HNPs) are synthesized in vivo as inactive precursor proteins, i.e. preproHNPs. A series of sequential proteolytic events excise the N-terminal inhibitory pro peptide, leading to defensin maturation and storage in azurophilic granules. The anionic pro peptide, required for correct sub-cellular trafficking and sorting of proHNPs, inhibits the antimicrobial activity of cationic defensins, either inter or intra-molecularly, presumably through charge neutralization. To better understand the role of the pro peptide in the folding and functioning of alpha-defensins and/or pro alpha-defensins, we chemically attached the proHNP1 pro peptide or (wt)pro peptide and the following artificial pro segments to the N terminus of HNP1: polyethylene glycol (PEG), Arg(10) (polyR), Ser(10) (polyS), and (cr)pro peptide, a charge-reversing mutant of the pro peptide where Arg/Lys residues were changed to Asp, and Asp/Glu residues to Lys. Comparative in vitro folding suggested that while all artificial pro segments chaperoned defensin folding, with PEG being the most efficient, the pro peptide catalyzed the folding of proHNPs likely through two independent mechanisms: solubilization of and interaction with the C-terminal defensin domain. Further, the N-terminal artificial pro segments dramatically altered the bactericidal activity of HNP1 against both Escherichia coli and Staphylococcus aureus. Surprisingly, (cr)pro peptide and (wt)pro peptide showed similar properties with respect to intra-molecular and inter-molecular catalysis of defensin folding as well as alpha-defensin binding, although their binding modes appeared different. Our findings identify a dual chaperone activity of the pro peptide and may shed light on the molecular mechanisms by which pro alpha defensins fold in vivo. PMID- 17355882 TI - Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia. AB - Alpha-11 giardin is a member of the multi-gene alpha-giardin family in the intestinal protozoan, Giardia lamblia. This gene family shares an ancestry with the annexin super family, whose common characteristic is calcium-dependent binding to membranes that contain acidic phospholipids. Several alpha giardins are highly expressed during parasite-induced diarrhea in humans. Despite being a member of a large family of proteins, little is known about the function and cellular localization of alpha-11 giardin, although giardins are often associated with the cytoskeleton. It has been shown that Giardia exhibits high levels of alpha-11 giardin mRNA transcript throughout its life cycle; however, constitutive over-expression of this protein is lethal to the parasite. Determining the three dimensional structure of an alpha-giardin is essential to identifying functional domains shared in the alpha-giardin family. Here we report the crystal structures of the apo and Ca(2+)-bound forms of alpha-11 giardin, the first alpha giardin to be characterized structurally. Crystals of apo and Ca(2+)-bound alpha-11 giardin diffracted to 1.1 A and 2.93 A, respectively. The crystal structure of selenium substituted apo alpha-11 giardin reveals a planar array of four tandem repeats of predominantly alpha-helical domains, reminiscent of previously determined annexin structures, making this the highest-resolution structure of an annexin to date. The apo alpha-11 giardin structure also reveals a hydrophobic core formed between repeats I/IV and II/III, a region typically hydrophilic in other annexins. Surprisingly, the Ca(2+)-bound structure contains only a single calcium ion, located in the DE loop of repeat I and coordinated differently from the two types of calcium sites observed in previous annexin structures. The apo and Ca(2+) bound alpha-11 giardin structures assume overall similar conformations; however, Ca(2+)-bound alpha-11 giardin crystallized in a lower-symmetry space group with four molecules in the asymmetric unit. Vesicle-binding studies suggest that alpha 11 giardin, unlike most other annexins, does not bind to vesicles composed of acidic phospholipids in a calcium-dependent manner. PMID- 17355883 TI - How the N-terminal domain of the OSCP subunit of bovine F1Fo-ATP synthase interacts with the N-terminal region of an alpha subunit. AB - The peripheral stalk of ATP synthase acts as a stator holding the alpha(3)beta(3) catalytic subcomplex and the membrane subunit a against the torque of the rotating central stalk and attached c ring. In bovine mitochondria, the N terminal domain of the oligomycin sensitivity conferral protein (OSCP-NT; residues 1-120) anchors one end of the peripheral stalk to the N-terminal tails of one or more alpha subunits of the F(1) subcomplex. Here, we present an NMR characterisation of the interaction between OSCP-NT and a peptide corresponding to residues 1-25 of the alpha-subunit of bovine F(1)-ATPase. The interaction site contains adjoining hydrophobic surfaces of helices 1 and 5 of OSCP-NT binding to hydrophobic side-chains of the alpha-peptide. PMID- 17355884 TI - Apomorphine effects on frog locomotor behavior. AB - The neuroanatomical pathways of the DA systems have been shown to be largely conserved across many vertebrate taxa. It is less certain whether the structural similarities seen between mammals and amphibians reflect a similar functional homology. DA is well known for its role in facilitating motor behaviors in mammals. We examined whether a similar role for DA exists in amphibians using the Northern Leopard Frog (Rana pipiens). We investigated the effects of the nonspecific DA agonist, apomorphine (APO) on a complex motor task that included two distinct components known to be differentially modulated by DA in mammals: swimming and climbing. We demonstrated that a high single dose of APO (20 mg/kg, body weight) strongly increased the amount of time spent completing the motor task. Furthermore, we showed that although APO did not significantly alter several aspects of swimming behavior, two aspects of climbing behavior were disrupted. Both climbing speed and climbing ability were impaired by APO treatment. These results increase our understanding of DA function in amphibians and add to our understanding of structure-function homologies of dopamine function across vertebrate taxa. PMID- 17355885 TI - Catadioptric stereo-vision system for the real-time monitoring of 3D behavior in aquatic animals. AB - Fish species have been used as vertebrate model systems for numerous human diseases. However, a comprehensive monitoring system for continuously tracking the positions of aquatic animals is still lacking. Manual or simple automatic methods usually lead to false or incomplete behavioral parameters. In this paper, a video-based 3D system is proposed for monitoring aquatic animals. This system is comprised of a novel catadioptric stereo-vision setup and methods for robust tracking of 3D motion-related behavior. The system has many advantages over 2D monitoring methods, such as being able to completely monitor the animals' behavior in 3D space with high spatial and temporal resolution, track multiple animals simultaneously without any physical marker, and accurately reconstruct 3D motion trajectories despite the potential problems of water refraction and reflection. Alterations in swimming behavior following exposure to acute ethanol were studied in goldfish (Carassius auratus) using the 3D behavior monitoring system. In analyzing the experimental data, a systematic comparison was made between the 3D goldfish behavioral parameters and their dimensionally reduced 2D forms. It was found that the 3D monitoring method was able to generate more accurate behavioral parameters than the conventional 2D methods. Compared to the results from 3D method, the hypothesis test conclusions based on 2D methods are more prone to error. It is expected that the 3D behavior monitoring system can significantly improve the efficiency, accuracy, and cost-effectiveness of behavioral studies and of model development in aquatic animals; potential applications include pre-clinical drug development, in-vivo compound screening, and bio-sensing. PMID- 17355886 TI - Escape of human immunodeficiency virus type 1 from broadly neutralizing antibodies is not associated with a reduction of viral replicative capacity in vitro. AB - Although the majority of primary HIV-1 variants can be neutralized by broadly neutralizing antibodies such as b12, 2G12, 2F5 and 4E10, resistance to these antibodies has been reported as well. The ability of the broadly neutralizing antibodies to inhibit a variety of viruses suggests that their epitopes are conserved and escape from these antibodies may thus come at a cost to viral fitness. Here we demonstrate that resistance to broadly neutralizing antibodies was in general not associated with a reduced replicative capacity of the virus in vitro. This indicates that loss of replicative capacity due to escape from broadly neutralizing antibodies may be limited. PMID- 17355887 TI - Comparison between alternating aerobic-anoxic and conventional activated sludge systems. AB - Conventional activated sludge systems ensure removal of colloidal and dissolved carbonaceous organic matter whereas alternating aerobic-anoxic systems, in addition, satisfy a further reduction in nitrogen content of wastewater. Main difference between them is that the alternating system should also include an anoxic operation mode which satisfies denitrification. In other words conventional systems are operated under aerobic conditions whereas alternating systems require a periodical change from aerobic conditions to anoxic conditions. So the most important problem in alternating systems is to find the appropriate durations for both sequences. In this study a comparison between conventional and alternating systems is considered in terms of nitrogen removal and aeration time by simulation under the same conditions together with an optimization algorithm. The results show that an activated sludge system can be operated as an alternating aerobic-anoxic system so that nitrogen removal is also possible during treatment without any additional investment or operational cost. PMID- 17355888 TI - Chemical vulnerability of red soils in La Mancha (Central Spain). AB - Red soils are widely distributed in Mediterranean regions. They constitute one of the most important soil resources for crop production and other uses. The main objective of this paper is to estimate the inherent chemical susceptibility of red soils of La Mancha to chemical degradation. Selected 47 soil profiles, were analyzed in the area by means of multivariate analysis; we identified five soil attributes that are well represented in the local soils database, which are most likely to control the chemical vulnerability. These attributes are the calcium carbonate, organic matter and clays together with soil depth and drainage. The attributes were transformed and a simple vulnerability index (VI) was deviced. We concluded that the index may be used as a first approximation rating of La Mancha's red soils vulnerability against an eventual chemical degradation, or to aid resource management and prevent anthropogenic potential impacts. PMID- 17355889 TI - Outcomes in surgical stage I uterine papillary serous carcinoma. AB - OBJECTIVE: The optimal management of patients with stage I uterine papillary serous carcinoma (UPSC) is unclear. We sought to determine whether outcomes of women with surgical stage I UPSC differ with and without adjuvant therapy. METHODS: Retrospective multi-institution analysis of women with stage I UPSC surgically staged from 1976 to 2006. INCLUSION CRITERIA: comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, selective pelvic/aortic lymphadenectomy, peritoneal cytology. Recurrence and survival were analyzed using Kaplan-Meier method. RESULTS: Of 83 women with stage I UPSC, 36 (43%) received adjuvant therapies (23% radiotherapy, 3% chemotherapy, 15% chemotherapy and radiotherapy, 2% progestins). Three-year overall (OS) and progression-free survival (PFS) were 80% and 68%, respectively. Three-year OS and PFS by adjuvant treatment were observation (N=47) 86% and 78%, radiotherapy (N=17) 63% and 44%, chemotherapy with or without radiotherapy (N=17) 92% and 76%, respectively. Of the 18 recurrences, 9 (50%) included an extrapelvic component. Local recurrence was 2/30 (7%) following adjuvant radiotherapy and 7/53 (13%) without radiotherapy (p=0.48). Recurrence was higher in stage IB/IC (15/51, 29%) compared to stage IA (3/32, 9%). There has been one recurrence (5%) among the 22 women observed with stage IA disease. CONCLUSION: In this largest reported series of women with surgical stage I UPSC, the high recurrence (29%) among patients with stage IB/IC disease highlights the need for clinical trials to test new therapeutic approaches. Surgically staged patients with IA disease had good prognosis. These data suggest that radiotherapy alone is not effective, that systemic therapy is needed, and that observation could be considered in patients with stage IA disease. PMID- 17355890 TI - Quality of life in long-term survivors of ovarian germ cell tumors: a Gynecologic Oncology Group study. AB - PURPOSE: This report describes the strength and significance of the association between antecedent and mediating variables across four categories of quality of life (QOL) outcomes in 132 disease free women with ovarian germ cell survivors. METHODS: Survivors (n=132) participated in a mailed questionnaire and computer assisted telephone survey. Participants in four prospective GOG protocols were contacted their treating physician for verbal consent to be approached by investigators at the Indiana University Cancer Center about a quality of life study. Similar patients treated at the MD Anderson Cancer Center were also included. If women verbally consented after being contacted by investigators at Indiana University, an informed consent and questionnaire packet was sent via mail. After return of the written informed consent and background questionnaire, a trained research assistant scheduled a computer-assisted interview to complete data collection. RESULTS: Median follow-up from diagnosis was 10.2 years. Mediating variables of self-efficacy or social support played a significant role (p=0.05 to p=0.001) in all four QOL categories: physical functioning, psychological functioning, sexual functioning, and spiritual functioning. Being a younger age at diagnosis and married were positively related to sexual functioning (p=0.05). Menstrual and gynecological symptoms were inversely related. IMPLICATIONS: Results indicate that clinicians may want to be especially sensitive to identifying a survivor's social support and confidence (self efficacy) in handling issues evolving from treatment since these skills may be related to overall quality of life outcomes. PMID- 17355891 TI - Clozapine treatment reverses dizocilpine-induced deficits of pre-pulse inhibition of tactile startle response. AB - Pre-pulse inhibition (PPI) is a phenomenon of neurobehavioral plasticity in which the motor response to a startling sensory stimulus is inhibited by a preceding sensory stimulus of a lower intensity. The current experiment used tactile startle rather than acoustic startle to determine the generality of PPI across sensory modalities. PPI is easily modeled in experimental animals and serves as a useful method for determining the neural bases for sensorimotor plasticity, which can be disturbed in sensory modulation disorders. In the current study, female Sprague-Dawley rats were tested for tactile startle PPI after an auditory pre pulse. The glutamate NMDA receptor antagonist dizocilpine (MK-801, 0.05 mg/kg) caused a nearly total blockade of the PPI effect (p<0.0005). The antipsychotic drug clozapine (1.25 mg/kg, p<0.001 and 2.5 mg/kg p<0.05) significantly attenuated the dizocilpine-induced PPI impairment. Interestingly, the lower clozapine dose did not by self enhance PPI and the higher clozapine dose when given alone caused a significant (p<0.05) PPI impairment relative to control. Nicotine (0.2 and 0.4 mg/kg) did not significantly interact with the other treatments, though the higher nicotine dose did show a trend toward attenuating the PPI impairment caused by the high clozapine dose. These effects were replicated in a second experiment of clozapine-dizocilpine interactions without nicotine treatment. This study shows that PPI of tactile startle is dramatically impaired by blocking NMDA activation and that the prototypic atypical antipsychotic drug clozapine can correct this deficit. This may be relevant to the action of clozapine in attenuating sensory gating deficits in schizophrenia and may point to new avenues of treatment for sensory modulation disorders in which there is excessive tactile response. PMID- 17355892 TI - Oxidative stress and pregnancy outcome: a workshop report. PMID- 17355893 TI - Method to enhance transfection efficiency of cell lines and placental fibroblasts. AB - We report a method that allows for a 2-9-fold increase in transfection efficiency compared to the standard cationic lipid-based protocol. The method involves a brief incubation of freshly trypsinized cells with transfection complexes, followed by incubation in cell growth medium containing serum and antibiotics. The method is simple, cost-effective, and can be applied to both DNA and siRNA transfections as well as to a variety of cell types including hard-to-transfect human placental fibroblasts. PMID- 17355894 TI - Barnase-barstar high affinity interaction phenomenon as the base for the heterogenous bioluminescence pseudorabies virus' immunoassay. AB - The effective new variant of "sandwich" bioluminescent enzyme immunoassay (BEIA) for the sensitive detection of glycoprotein B (gB) of pseudorabies virus (PrV) was presently developed. The high affinity interaction of barnase-barstar protein pair and photoprotein obelin as bioluminescent marker were for the first time successfully applied to BEIA development. Preliminary the two monoclonal antibodies, 11/5 and 34/2, were raised against gB for ELISA PrV detection. Presently we used the same immuno-"sandwich" principle for BEIA. To do this the two different bioconjugates were elaborated. Recombinant barnase was chemically conjugated with monoclonal anti-PrV's gB IgG, and also barstar was fused in frame to obelin. The characteristics of BEIA method have been compared to ELISA PrV detection. We have shown the proposed here gB-BEIA was 40-fold more sensitive as opposed to gB-ELISA test. The construction might have a broad promise in multiple potential immunological applications. PMID- 17355895 TI - Video-assisted thoracic surgical resection of giant cardiac lipoma: a case report. AB - We describe the case of a 73-year-old man, with a history of previous coronary artery by-pass, who presented at our division for new onset of angina, hypotension and dyspnea due to a primary giant para-cardiac lipoma. The success of complete resection of the mass achieved by means of video-assisted thoracic surgical procedure demonstrated the efficacy and safeness of this method in the treatment of benign cardiac tumours. PMID- 17355896 TI - Effect of a previous heat shock on the thermal resistance of Listeria monocytogenes and Pseudomonas aeruginosa at different pHs. AB - In this work we study the effect of heat shocks of various durations up to 60 min, at different temperatures between 35 and 45 degrees C, in media of pH 4.0, 5.5 and 7.4 on the heat resistance of Listeria monocytogenes and Pseudomonas aeruginosa. The pattern of survival curves after heat treatment did not change with the application of a previous heat shock. However, the kinetics of inactivation was different for the two microorganisms studied. Whereas the inactivation of L. monocytogenes was similar to an exponential function of heating time and therefore straight survival curves were obtained, survival curves corresponding to P. aeruginosa showed convex profiles. All survival curves obtained in this investigation were fitted to Weibull-based Mafart equation: log(10)S(t)=-(t / delta)(p). The magnitude of the heat shock induced thermotolerance increased with treatment medium pH. At pH 7.4 the increase in heat tolerance depended on the duration and temperature of the heat shock. On the contrary, at pH 5.5 and pH 4.0, the heat-shock temperature did not exert any effect. The observed maximum delta values increased 2.3, 4.0 and 9.3 fold for L. monocytogenes, and 1.3, 2.1 and 8.4 fold for P. aeruginosa, at pH 4.0, 5.5 and 7.4, respectively. This research has proven that Mafart equation allows studying and quantifying the effect of heat shocks on bacterial heat resistance. PMID- 17355897 TI - Modeling the complexity of post-treatment drinking: it's a rocky road to relapse. AB - The most widely cited road block to successful treatment outcomes for psychological and substance use disorders has been described as the return to the previous behavior, or "relapse." The operational definition of "relapse" varies from study to study and between clinicians, but in general the term is used to indicate the return to previous levels of symptomatic behavior. One explanation for the variation in the operationalization of relapse is the wide variety of behaviors for which the term is applied, including (but not limited to): depression, substance abuse, schizophrenia, mania, sexual offending, risky sexual behavior, dieting, and the anxiety disorders. A second explanation for the multitude of definitions for relapse is the inherent complexity in the process of behavior change. In this paper we present the most recent treatment outcome research evaluating relapse rates, with a special focus on the substance use disorders. Following this review of the literature we present an argument for the operationalization of relapse as a dynamic process, which can be empirically characterized using dynamical systems theory. We support this argument by presenting results from the analysis of alcohol treatment outcomes using catastrophe modeling techniques. These results demonstrate the utility of catastrophe theory in modeling the alcohol relapse process. The implications of these analyses for the treatment of alcohol use disorders, as well as a discussion of future research incorporating nonlinear dynamical systems theory is provided. PMID- 17355898 TI - Prevention of depression in youth: a qualitative review and future suggestions. AB - Since 1990, significant efforts have been made towards developing interventions to prevent depression in youth. Meta-analyses of preventive interventions have consistently yielded small but significant effect sizes in the short-term prevention of depression. However, the maintenance of intervention effects over extended follow-ups ranging from 6 months to 3 years has not been consistently demonstrated. In this qualitative review, significant methodological issues that continue to be of concern are discussed. Illustrative studies are described to highlight the accomplishments and limitations of interventions to date. Particular areas in need of attention include the implementation of booster sessions, use of appropriate statistical analyses, examination of multiple outcome variables, augmentation of protective factors, and exploration of mediators and moderators of intervention effects. Future directions for the field of depression prevention are outlined. PMID- 17355899 TI - Real life is different: a qualitative study of why women delay abortion until the second trimester in Vietnam. AB - Although legal and safe-induced abortion services are available on request in Vietnam, second-trimester abortion still occurs. Given the increased risks and higher costs associated with later-term abortions, we conducted a qualitative study to understand the determinants of delaying abortion until the second trimester. We used purposive sampling to conduct semi-structured face-to-face interviews with 60 women aged 14-47 receiving an abortion at 13-24 weeks of gestation in 5 health facilities in 3 provinces in Vietnam. We also interviewed 6 providers from the study facilities. Three broad categories for factors influencing delays in obtaining abortions emerged: most women failed to recognize their pregnancy during the first trimester; women described structural barriers to accessing services earlier; and some women either needed time to make a decision or only decided to abort after other events had transpired. A richer understanding of the factors that prevent women from obtaining an abortion during the first trimester could be useful for informing interventions that support women in receiving care earlier during their pregnancies. PMID- 17355900 TI - There's no place like (a) home: ontological security among persons with serious mental illness in the United States. AB - As the homelessness 'crisis' in the United States enters a third decade, few are as adversely affected as persons with serious mental illness. Despite recent evidence favoring a 'housing first' approach, the dominant 'treatment first' approach persists in which individuals must climb a ladder of program requirements before becoming eligible for an apartment of their own. Drawing upon the concept of 'ontological security', this qualitative study examines the subjective meaning of 'home' among 39 persons who were part of a unique urban experiment that provided New York City's homeless mentally ill adults with immediate access to independent housing in the late 1990s. The study design involved purposively sampling from the experimental (housing first) group (N=21) and the control (treatment first) group (N=18) and conducting two life history interviews with each participant. Markers of ontological security-constancy, daily routines, privacy, and having a secure base for identity construction provided sensitizing concepts for grounded theory analyses designed to also yield emergent, or new, themes. Findings revealed clear evidence of the markers of ontological security among participants living in their own apartments. This study expands upon previous research showing that homeless mentally ill persons are capable of independent living in the community. The emergent theme of 'what's next' questions and uncertainty about the future points to the need to address problems of stigma and social exclusion that extend beyond the minimal achievement of having a 'home'. PMID- 17355901 TI - Evaluation of the chronic disease self-management program (CDSMP) among chronically ill older people in the Netherlands. AB - Many chronically ill older patients in the Netherlands have a combination of more than one chronic disease. There is therefore a need for self-management programs that address general management problems, rather than the problems related to a specific disease. The Chronic Disease Self-Management Program (CDSMP) seems to be very suitable for this purpose. In evaluations of the program that have been carried out in the United States and China, positive effects were found on self management behaviour and health status. However, the program has not yet been evaluated in the Netherlands. Therefore, the aim of this study was to evaluate the short-term and longer-term effects of the program among chronically ill older people in the Netherlands. One hundred and thirty-nine people aged 59 or older, with a lung disease, a heart disease, diabetes, or arthritis were randomly assigned to an intervention group (CDSMP) or a control group (care-as-usual). Demographic data and data on self-efficacy, self-management behaviour and health status were collected at three measurement moments (baseline, after 6 weeks, and after 6 months). The patients who participated rated the program with a mean of 8.5 points (range 0-10), and only one dropped out. However, our study did not yield any evidence for the effectiveness of the CDSMP on self-efficacy, self management behaviour or health status of older patients in the Netherlands. Because the patients who participated were very enthusiastic, which was also indicated by very high mean attendance (5.6 out of 6 sessions) and only one dropout, it seems too early to conclude that the program is not beneficial for these patients. PMID- 17355902 TI - Land use change and population growth in the Morobe Province of Papua New Guinea between 1975 and 2000. AB - The relation between human population growth and land use change is much debated. Here we present a case study from Papua New Guinea where the population has increased from 2.3 million in 1975 to 5.2 million in 2000. Since 85% of the population relies on subsistence agriculture, population growth affects agricultural land use. We assessed land use change in the Morobe province (33,933 km2) using topographic maps of 1975 and Landsat TM images of 1990 and 2000. Between 1975 and 2000, agricultural land use increased by 58% and population grew by 99%. Most new agricultural land was taken from primary forest and the forest area decreased from 9.8 ha person(-1) in 1975 to 4.4 ha person(-1) in 2000. Total population change and total land use change were strongly correlated. Most of the agricultural land use change occurred on Inceptisols in areas with high rainfall (>2500 mm year(-1)) on moderate to very steep slopes (10-56%). Agricultural land use changes in logged-over areas were in the vicinity of populated places (villages), and in close proximity to road access. There was considerable variation between the districts but districts with higher population growth also had larger increases in agricultural areas. It is concluded that in the absence of improved farming systems the current trend of increased agriculture with rapid population growth is likely to continue. PMID- 17355903 TI - Leishmanicidal activity of Pentalinon andrieuxii. AB - Extracts of the root of Pentalinon andrieuxii, vernacular name of "contrahierva" (solen ak' in Mayan language, were investigated for their lethal effect on the protozoa Leishmania mexicana. The hexanes extract was highly effective to delay and eventually stop parasite survival. PMID- 17355904 TI - Prokaryotic origins of the non-animal peroxidase superfamily and organelle mediated transmission to eukaryotes. AB - Members of the superfamily of plant, fungal, and bacterial peroxidases are known to be present in a wide variety of living organisms. Extensive searching within sequencing projects identified organisms containing sequences of this superfamily. Class I peroxidases, cytochrome c peroxidase (CcP), ascorbate peroxidase (APx), and catalase peroxidase (CP), are known to be present in bacteria, fungi, and plants, but have now been found in various protists. CcP sequences were detected in most mitochondria-possessing organisms except for green plants, which possess only ascorbate peroxidases. APx sequences had previously been observed only in green plants but were also found in chloroplastic protists, which acquired chloroplasts by secondary endosymbiosis. CP sequences that are known to be present in prokaryotes and in Ascomycetes were also detected in some Basidiomycetes and occasionally in some protists. Class II peroxidases are involved in lignin biodegradation and are found only in the Homobasidiomycetes. In fact class II peroxidases were identified in only three orders, although degenerate forms were found in different Pezizomycota orders. Class III peroxidases are specific for higher plants, and their evolution is thought to be related to the emergence of the land plants. We have found, however, that class III peroxidases are present in some green algae, which predate land colonization. The presence of peroxidases in all major phyla (except vertebrates) makes them powerful marker genes for understanding the early evolutionary events that led to the appearance of the ancestors of each eukaryotic group. PMID- 17355905 TI - The absence of expression of the three isoenzymes of the inositol 1,4,5 trisphosphate 3-kinase does not prevent the formation of inositol pentakisphosphate and hexakisphosphate in mouse embryonic fibroblasts. AB - The activation of phospholipase C leads to the formation of both I(1,4,5)P(3) and diacylglycerol (DAG). I(1,4,5)P(3) can be metabolized by dephosphorylation catalyzed by Type I I(1,4,5)P(3) 5-phosphatase and by enzymatic phosphorylation to various inositol phosphates. This last step is catalyzed by three mammalian isoenzymes that specifically phosphorylate the 3-phosphate position of the inositol ring Itpka, Itpkb and Itpkc and a less specific enzyme Ipmk (or inositol multikinase) that phosphorylates I(1,4,5)P(3) at the D-3 and D-6 positions. This study was performed in mice cells in order to understand the synthetic pathway of IP5 and IP6 following PLC stimulation and possible link with Itpk activity. Mouse embryonic fibroblasts (MEF) were prepared from Itpkb(-/-) Itpkc(-/-) mice. Western blot and RT-PCR analysis show that the cells do not express Itpka. In contrast, they do express Ipmk. The cells still produce IP5 and IP6. Our data show that the absence of expression of the three isoenzymes of Itpk does not prevent the formation of IP5 and IP6, at least in mouse embryonic fibroblasts. The nuclear Ipmk plays therefore a critical role in the metabolism of I(1,4,5)P(3) and production of highly phosphorylated IP5 and IP6. PMID- 17355906 TI - Biological roles of anti-GM1 antibodies in patients with Guillain-Barre syndrome for nerve growth factor signaling. AB - To reveal the biological and pathological roles of anti-GM1 antibody in Guillain Barre syndrome (GBS), we examined its effects on nerve growth factor (NGF) induced TrkA autophosphorylation (NGF-TrkA signaling) in PC12 cells, a sympathetic nerve cell line. The NGF-TrkA signaling is enhanced by exogenous GM1 ganglioside and this phenomenon is regarded as one of the functional aspects of GM1. The IgGs purified from patients' sera inhibited the NGF-TrkA signaling in GM1 pre-incubated PC12 cells. The degrees of inhibition by IgGs from patients paralleled their immunological reactivity to GM1. In addition, the IgGs also inhibited the neurite outgrowth of NGF-treated PC12 cells. Immunoglobulins in the rabbit sera, which were immunized by GM1, also caused a similar suppressive phenomenon. These results suggested that the anti-GM1 antibody could play roles in pathophysiology in anti-GM1 antibody positive GBS through interfering with the neurotrophic action of NGF and GM1 mediated signal modulation including NGF-TrkA signaling. It is suggested that the modulation of GM1 function is one important action of antibodies and could be one of the important mechanisms in GBS. PMID- 17355908 TI - The roles of prefrontal and posterior parietal cortex in algebra problem solving: a case of using cognitive modeling to inform neuroimaging data. AB - In naturalistic algebra problem solving, the cognitive processes of representation and retrieval are typically confounded, in that transformations of the equations typically require retrieval of mathematical facts. Previous work using cognitive modeling has associated activity in the prefrontal cortex with the retrieval demands of algebra problems and activity in the posterior parietal cortex with the transformational demands of algebra problems, but these regions tend to behave similarly in response to task manipulations (Anderson, J.R., Qin, Y., Sohn, M.-H., Stenger, V.A., Carter, C.S., 2003. An information-processing model of the BOLD response in symbol manipulation tasks. Psychon. Bull. Rev. 10, 241-261; Qin, Y., Carter, C.S., Silk, E.M., Stenger, A., Fissell, K., Goode, A., Anderson, J.R., 2004. The change of brain activation patterns as children learn algebra equation solving. Proc. Natl. Acad. Sci. 101, 5686-5691). With this study we attempt to isolate activity in these two regions by using a multi-step algebra task in which transformation (parietal) is manipulated in the first step and retrieval (prefrontal) is manipulated in the second step. Counter to our initial predictions, both brain regions were differentially active during both steps. We designed two cognitive models, one encompassing our initial assumptions and one in which both processes were engaged during both steps. The first model provided a poor fit to the behavioral and neural data, while the second model fit both well. This simultaneously emphasizes the strong relationship between retrieval and representation in mathematical reasoning and demonstrates that cognitive modeling can serve as a useful tool for understanding task manipulations in neuroimaging experiments. PMID- 17355907 TI - The TSC1 gene product hamartin interacts with NADE. AB - Hamartomatous brain lesions are a hallmark of brain pathology of tuberous sclerosis complex (TSC). To elucidate the mechanism of tumor development in the brain of TSC, we identified NADE (p75NTR-associated cell death executor) as an interactor for TSC1 gene product hamartin using a yeast two-hybrid system. In a pull-down assay, endogenous NADE was purified with the immobilized coiled-coil domain (CCD) of hamartin from the PC12h cell lysate. Immunofluorescence and immunoprecipitation confirmed the interaction of hamartin and NADE in cultured neurons and mouse brain lysate. Hamartin constitutively associated with NADE to prevent its proteasomal degradation. Suppression of hamartin with TSC1 small interfering RNA (siRNA) caused reduction of NADE and failed to lead to NGF induced apoptosis in PC12h cells. These results indicate that hamartin binds to NADE to regulate neuronal cell function and loss of this association is likely to contribute to the brain pathology in TSC. PMID- 17355909 TI - Early cortical response to behaviorally relevant absence of anticipated outcomes: a human event-related potential study. AB - Animals with lesions of the orbitofrontal cortex (OFC) have an extinction and reversal learning deficit. Humans with OFC lesions have similar deficits and often continue to act according to currently inappropriate memories. We tested when the human brain distinguishes between confirmed and negated outcomes of anticipations. Eleven participants predicted behind which one of two rectangles an object drawing was hidden while their cerebral activity was recorded from 123 surface electrodes. We found that absence of the predicted outcome induced specific electrical field topographies between 190 ms-300 ms and 380 ms-600 ms. Behaviorally irrelevant deviation from predicted outcomes did not induce these alterations. Distributed linear inverse solutions indicated that the source of the early electric field topography after negated predictions differed by additional left ventrolateral prefrontal activation. The late differences in electrical field topographies were characterized by the selective absence of a processing stage in response to negated predictions. The study indicates early, specific cortical processing of behaviorally relevant absence of predicted outcomes. PMID- 17355910 TI - Contextual interference in recognition memory with age. AB - Previous behavioral research suggests that although elderly adults' memory benefits from supportive context, misleading or irrelevant contexts produce greater interference. In the present study, we use event-related fMRI to investigate age differences when processing contextual information to make recognition judgments. Twenty-one young and twenty elderly incidentally encoded pictures of objects presented in meaningful contexts, and completed a memory test for the objects presented in identical or novel contexts. Elderly committed more false alarms than young when novel objects were presented in familiar, but task irrelevant, contexts. Elderly showed reduced engagement of bilateral dorsolateral prefrontal cortex and anterior cingulate relative to young, reflecting disruption of a cognitive control network for processing context with age. Disruption occurred for both high and low-performing elderly, suggesting that cognitive control deficits are pervasive with age. Despite showing disruption of the cognitive control network, high-performing elderly recruited additional middle and medial frontal regions that were not recruited by either low-performing elderly or young adults. This suggests that high-performing elderly may compensate for the disruption of the cognitive control network by recruiting additional frontal resources to overcome cognitive control deficits that affect recognition memory. PMID- 17355911 TI - Encoding of the cough reflex. AB - Coughing can be both voluntarily induced and involuntarily initiated by activation of vagal afferent nerves innervating the airways and lungs. Centrally, cough is regulated at the level of the brainstem through integration of vagal afferent nerve input by relay neurones in the nucleus tractus solitarius (nTS). Projections to and from the nTS add further complexity to cough regulation, as do the profound influences of psychological and social factors known to regulate cough. Peripherally, both neuronal and non-neuronal elements in the airways regulate the excitability of the vagal afferent nerve terminals regulating cough. These multiple levels of integration and encoding of the cough reflex may render this defensive respiratory response highly susceptible to modulation both by disease processes and through therapeutic intervention. PMID- 17355912 TI - Long-acting neuroleptics used in wildlife management do not impair thermoregulation or physical activity in goats (Capra hircus). AB - Long-acting neuroleptics commonly are used in wildlife management to decrease stress-related mortality in wild animals, but with possible effects on thermoregulation, which may contribute to residual morbidity and mortality. We investigated the effects of haloperidol (0.01, 0.1, 1 mg kg(-1), n=4), zuclopenthixol (0.1, 1, 10 mg kg(-1), n=4) and perphenazine (0.1, 1, 10 mg kg( 1), n=8), as well as control injections of sunflower oil, on body temperature and physical activity of laboratory goats under hot, cold and thermoneutral ambient temperatures. Implanted data loggers continuously recorded abdominal temperature, and data loggers attached externally on the foreleg recorded movement of unrestrained goats, in a climatic chamber at 35 degrees C, 10 degrees C and 22 degrees C. Cycling ambient temperature between 35 degrees C in daytime and 10 degrees C at night time caused a significant increase in amplitude of the circadian rhythm of body temperature in goats given sunflower oil (P=0.0012, unpaired t-test, n=8), but the administration of zuclopenthixol or perphenazine did not affect this change in amplitude (P>0.05, two-way ANOVA, n=4). Mean daily body temperature after administration of zuclopenthixol or perphenazine, and mean daily activity after zuclopenthixol administration, were not significantly different to those after control injections, at any ambient temperature, for the expected duration of drug activity (all P>0.05, two-way ANOVA, n=4). Thermal response indices, and mean activity, during heat, cold or thermoneutral exposure, of goats for 7 h after haloperidol injection, were not significantly different, at any dose or any ambient temperature, to those following control injections (all P>0.05, repeated measures ANOVA, n=4). Long-acting neuroleptics did not impair activity or thermoregulation of goats subjected to inescapable thermal challenges. PMID- 17355913 TI - Tyrosinase and ocular diseases: some novel thoughts on the molecular basis of oculocutaneous albinism type 1. AB - Tyrosinase (TYR) is a multifunctional copper-containing glycoenzyme (approximately 80 kDa), which plays a key role in the rate-limiting steps of the melanin biosynthetic pathway. This membrane-bound protein, possibly evolved by the fusion of two different copper-binding proteins, is mainly expressed in epidermal, ocular and follicular melanocytes. In the melanocytes, TYR functions as an integrated unit with other TYR-related proteins (TYRP1, TYRP2), lysosome associated membrane protein 1 (LAMP1) and melanocyte-stimulating hormone receptors; thus forming a melanogenic complex. Mutations in the TYR gene (TYR, 11q14-21, MIM 606933) cause oculocutaneous albinism type 1 (OCA1, MIM 203100), a developmental disorder having an autosomal recessive mode of inheritance. In addition, TYR can act as a modifier locus for primary congenital glaucoma (PCG) and it also contributes significantly in the eye developmental process. Expression of TYR during neuroblast division helps in later pathfinding by retinal ganglion cells from retina to the dorsal lateral geniculate nucleus. However, mutation screening of TYR is complicated by the presence of a pseudogene TYR like segment (TYRL, 11p11.2, MIM 191270), sharing approximately 98% sequence identity with the 3' region of TYR. Thus, in absence of a full-proof strategy, any nucleotide variants identified in the 3' region of TYR could actually be present in TYRL. Interestingly, despite extensive search, the second TYR mutation in 15% of the OCA1 cases remains unidentified. Several possible locations of these "uncharacterized mutations" (UCMs) have been speculated so far. Based on the structure of TYR gene, its sequence context and some experimental evidences, we propose two additional possibilities, which on further investigations might shed light on the molecular basis of UCMs in TYR of OCA1 patients; (i) partial deletion of the exons 4 and 5 region of TYR that is homologous with TYRL and (ii) variations in the polymorphic GA complex repeat located between distal and proximal elements of the human TYR promoter that can modulate the expression of the gene leading to disease pathogenesis. PMID- 17355914 TI - Various patterns of gestes antagonistes in cervical dystonia. AB - In this study, we evaluated patterns, quantity and effectiveness of gestes antagonistes, the association between the severity of disease and the type of gestes and the clinical implications of the presence of gestes antagonistes in 33 patients with cervical dystonia, 19 patients (58%) presented a classic sensory trick (ST) while 14 subjects (42%) demonstrated a forcible trick (FT). FTs prevailed in patients with more severe dystonia whereas STs were more common among patients with milder disease. These results suggest that at more severe stages of the disease, classic STs are not effective enough and thus patients use FTs. PMID- 17355915 TI - Electrical properties of neurons in the intact rat major pelvic ganglion. AB - The aim of this investigation was to characterize the electrical properties of neurons in the rat major pelvic ganglia (MPG) using intracellular recording techniques. MPG were dissected from male rats euthanized by isoflurane and thoracotomy. Neurons were classified as "phasic" or "tonic" according to their rate of accommodation during a 500-ms depolarizing current pulse. Phasic cells were further subdivided into rapidly or slowly adapting. The firing pattern of tonic cells was divided into regular high frequency, low frequency or irregular firing. In tonic cells, onset spikes showed TTX-resistant discharges; whereas sustained spikes were TTX sensitive. Changing the current pulse amplitude or the stimulation interval could alter the firing pattern in both types of neurons. Subthreshold membrane potential oscillations (SMPOs) were primarily observed when neurons were depolarized. SMPOs were Na(+) dependent and TTX sensitive. The majority of tonic and phasic neurons generated rebound spikes, most of which were partially Na(+) dependent. A small percentage (<6%) of neurons exhibited spontaneous activity. Taken together these findings are consistent with the concept that neurons in the MPG exhibit heterogeneous electrical properties. PMID- 17355916 TI - Magnetic resonance imaging findings in comparison with histopathology of heroin associated encephalopathy. AB - OBJECTIVE: To review the magnetic resonance imaging (MRI) features and explore the histopathological basis of heroin-associated encephalopathy (HE). METHODS: The data were collected from 34 established HE cases diagnosed with epidemiological evidence, clinical manifestations, MRI findings and laboratory examination. Histopathological sections were obtained in 10 cases. All patients were examined with T1WI, T2WI and FLAIR using 1.5T MRI scanner. Four patients died and autopsy was performed in 2 of them. Eight patients underwent stereotactic cerebral biopsy and the results of pathological examination were compared with the MRI findings. RESULTS: All the 34 cases had low signals in T1WI but high signals in T2WI. Extensive involvement of the hemispheres beyond the cerebellar tentorium, brain stem and cerebellum was identified in 85.3% of the cases, and less than 10% had lesions involving only one of these three structures. Most of the lesions involved mainly the white matter, and 91.2% of the cases showed involvement of the bilateral hemispheres. Specific MRI features were found to help in HE diagnosis: lesions compromising the hemispheres beyond the cerebellar tentorium presented with the pattern resembling the Chinese character "eight", a hollow pattern was found in brain stem involvement, and "butterfly wing" pattern in cerebellar involvement. The abnormal signals were caused mainly by demyelination and vacuole formation in the white matter, and these vacuoles resulted in the sponge-like appearance of the white matter containing fluid. CONCLUSION: MRI can provide strong evidence for HE diagnosis and can be informative of the involvement, position and aggravation of the lesions with some characteristic MRI features. In most of the cases, a MRI-based diagnosis can be consistent with histopathological diagnosis. PMID- 17355917 TI - [Isolation and characterization of human colorectal cancer cell subline with unique metastatic potential in the liver]. AB - OBJECTIVE: To isolate a subclone from human colorectal cancer cell line SW480 with unique metastatic potential in the liver. METHODS: Human colorectal cancer cells SW480 were implanted into BALB/c nude mice, and the hepatic metastatic lesions were harvested, and the tumor tissue blocks were re-implantated into nude mice for a second round of in vivo selection. The same procedure was repeated 5 times until a new cell subline, designated as SW480/M5, was established, whose biological behaviors was investigated both in vivo and in vitro. RESULTS: After orthotopic implantation of the tumor tissue into the colon of nude mouse for 28 days, widespread loco-regional and distant metastases occurred in mice inoculated with SW480 tissue, and those inoculated with SW480/M5 tissue had hepatic metastasis only. Compared with the parental cells, SW480/M5 cells were characterized by greater clonality, reproductive activity, motor ability, invasiveness, and weaker adhesive capacity to fibronectin. CONCLUSION: A human colorectal cancer cell subline with unique liver metastatic potential has been established by in vivo selection to serve as a new model for study ing colorectal cancer metastasis. PMID- 17355918 TI - [Preparation of recombinant Mycobacterium tuberculosis ESAT6-PPE68 fusion protein]. AB - OBJECTIVE: To construct esat6-ppe68 fusion gene and its prokaryotic expression vector for expression in E. coli. METHODS: With GeneSOEing method, a fusion gene was constructed by splicing esat6 gene and ppe68 gene and cloned into pGEX-4T-1 plasmid to construct the recombinant prokaryotic expression plasmid pGesat6 ppe68. After identification with restriction enzyme analysis, PCR and nucleotide sequencing analysis of the plasmid, E. coli BL21 was transformed with the recombinant plasmid and induced with IPTG to obtain the expression of the fusion protein ESAT6-PPE68 with GST-tag (about 69 kD), which were purified with GST fusion protein purification kit. The expression of esat6-ppe68 fusion gene was subsequently detected by SDS-PAGE and Western blot analysis. RESULTS: The sequence of esat6 and ppe68 in the recombinant plasmid was consistent with that in GenBank report. The fusion protein was detected in the cytoplasm in soluble form and represented approximately 40% of the total bacterial protein of E. coli. After purification, the purity of the fusion protein reached 90%, and its antigenicity was confirmed by Western blotting. CONCLUSION: The prokaryotic expression vector pGesat6-ppe68 has been constructed and the fusion protein ESAT6 PPE68 obtained successfully, which provides an experimental basis for potential application of the recombinant ESAT6-PPE68 in the diagnosis of tuberculosis. PMID- 17355919 TI - [ST6Gal I siRNA and antisense oligonucleotide-mediated gene silencing lowers the invasiveness potential of colonic carcinoma cells]. AB - OBJECTIVE: To study the effects of small interfering RNA (siRNA) and antisense oligonucleotides (ASOs) targeting ST6Gal I on adhesion and invasiveness of human colonic carcinoma cell line SW480 over-expressing ST6Gal I. METHODS: siRNA and ASOs targeting ST6Gal I were constructed and transfected into SW480 cells via lipofectmine 2000. SW480 cells were cultured and divided into 7 groups, namely the blank control group, liposome group, siRNA group (transfected with ST6Gal I siRNA), ASO(1) group (transfected with ST6Gal I ASO whose target site is different from the siRNA), ASO(2) group (transfected with ST6Gal I ASO targeting the same site as siRNA), siRNA+ASO(1) group (transfected with siRNA and ASO(1)), siRNA+ASO(2) group (transfected with siRNA and ASO(2)). RT-PCR was used to examine ST6Gal I mRNA expression following the treatment. Flow cytometry was used to examine the amount of alpha2,6-sialylation on SW480 cell surface. SW480 cell adhesion and invasiveness to the extracellular matrix (ECM) were analyzed using CytoMatrix kit and cell invasion assay kit, respectively. RESULTS: The expression of ST6Gal I mRNA, the amount of alpha2,6-sialylation on the cell surface and cell adhesion and invasion to ECM decreased remarkably in groups siRNA, ASO(1), ASO(2), siRNA+ASO(1) and siRNA+ASO(2), all significantly lower than those of the blank control and liposome groups (all P<0.05), especially in siRNA+ASO(1) group. Significant difference was noted between siRNA+ASO(1) and siRNA groups (P<0.05), but not between siRNA+ASO(2) and siRNA groups, or between blank control and liposome groups (all P>0.05). CONCLUSION: Chemically synthesized specific siRNA targeting ST6Gal I effectively inhibits SW480 cell ST6Gal I expression and leads to diminished cell adhesion and invasiveness to ECM, suggesting a combined effect of siRNA and ASO with different targeting sites. PMID- 17355920 TI - [In vitro expression of Lgeionella pneumophila pilE gene and its immunogenicity]. AB - OBJECTIVE: To construct a recombinant plasmid containing Lgeionella pneumophila pilE gene, detect its expression in NIH3T3 cells and evaluate its immunogenicity. METHODS: PilE gene (LP) was amplified from Legionella pneumophila DNA by PCR and inserted into pcDNA3.1(+) vector to construct the recombinant plasmid pcDNA3.1 pilE, which as verified by restriction endonuclease digestion, PCR and DNA sequencing analysis. NIH3T3 cells were transfected with the recombinant plasmid with Lipofection strategy. Transient and stable pilE gene products were detected by immunofluorescence and Western blotting, respectively. To evaluate the immunogenicity of pcDNA3.1-pilE, the recombinant plasmid was used as a DNA vaccine to immunize female BALB/c mice intramuscularly and the specific antibodies, lymphocyte proliferation response, interferon (IFN)-gamma production and cytotoxic T-lymphocyte response of the immunized mice were detected and evaluated. RESULTS: The pilE gene of 429 bp in length was amplified. After transfection of NIH3T3 cells with the recombinant plasmid, strong green fluorescence was observed on the cell membrane and inside the cell. A protein with relative molecular mass of 15.7 kD was detected in the transfected cells with Western blotting, suggesting successful protein expression of pilE gene. pcDNA3.1-pilE resulted in much stronger immune response in the immunized mice than pcDNA3.1(+) (P<0.01). CONCLUSION: The recombinant plasmid containing Lgeionella pneumophila pilE gene constructed in this study is capable of expression in NIH3T3 cells, and can induce specific humoral and cellular immune responses in mice. PMID- 17355921 TI - [Differentially expressed transcription factor-related genes in nasopharyngeal carcinoma and nasopharyngeal tissues]. AB - OBJECTIVE: To analyze the gene expression profiles of transcription factor related genes in nasopharyngeal carcinoma (NPC) tissues and normal nasopharyngeal tissues using a cDNA microarray membrane for exploring the regulatory mechanism of differential gene express in NPC tissues. METHODS: The total RNAs from 24 NPC tissues and 24 pooled normal nasopharyngeal tissues were reverse transcribed and labeled with alpha-(32)P-dCTP. The resultant cDNAs were hybridized to GF211 microarray, and the signals were analyzed by Pathway 4.0 software. RT-PCR was carried out to confirm the results. RESULTS: Among the 1625 differentially expressed genes detected in NPC and nasopharyngeal tissues, 35 transcription factor-related genes were identified with either up- or down-regulation. CONCLUSION: These differentially expressed transcription factor-related genes in NPC tissues might play a role in the regulation of NPC-related gene expression. PMID- 17355922 TI - [MMP-2/TIMP-2 expression in the trophoblasts of patients with gestational trophoblastic disease]. AB - OBJECTIVE: To explore the role of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of MMP-2 (TIMP-2) in the pathogenesis, development and prognosis of gestational trophoblastic disease (GTD). METHODS: In situ hybridization and immunohistochemistry were utilized for MMP-2/TIMP-2 mRNA and protein detection in normal chorion of women with early gestation, hydatidiform mole, invasive mole, or choricarcinoma. RESULTS: The results revealed that specific staining for mRNA and protein of MMP-2 and the expression of TIMP-2 was reduced in normal chorion of early gestation. In GTD ranging from hydatidiform mole, invasive mole to choricarcinoma, MMP-2 expression tended to increase while TIMP-2 expression underwent an invert change. The positivity rate of MMP-2 and TIMP-2 in gestational trophoblastic tumor group was higher than that of the normal chorion of early gestation group and hydatiform mole group (P<0.05 and P<0.001, respectively). CONCLUSION: A disrupted balance between the activation and inhibition of MMP-2 plays a critical role in the pathogenesis, progression and metastasis of GTD. PMID- 17355923 TI - [Therapeutic effect of Hongbeiyegen on alcohol-induced rat hepatic fibrosis]. AB - OBJECTIVE: To observe the therapeutic effect of Hongbeiyegen [the root of Alchornea trewioides(Benth.) Muell.-Arg.] on alcohol-induced liver fibrosis (AF) in rats and explore its mechanism. METHODS: In rats with AF, the serum levels of transforming growth factor beta1 (TGFbeta1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected along with examination of the changes in serum hyaluronic acid (HA), laminin (LN), procolagen type III (PC III), collagen type IV (C IV), glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST) levels. RESULTS: Compared with the control group, Hongbeiyegen could significantly reduce the levels of TGFbeta1, TIMP-1, HA, LN, PC III, CIV, ALT and AST in rats with AF. CONCLUSION: Hongbeiyegen can relieve and ameliorate liver fibrosis possibly by inhibiting the expression of TGFbeta1 and TIMP-1. PMID- 17355924 TI - [Green fluorescent protein as a tracer of bone marrow stromal cells in bone tissue engineering in rhesus]. AB - OBJECTIVE: To observe the role of green fluorescent protein (GFP) in tracing rhesus bone marrow stromal cells (rBMSCs) during tissue-engineered bone formation in vivo. METHODS: Ad5.CMV-GFP was amplified by infecting QBI-293A cells, and the bone marrow was harvested from the ilium of adult male rhesus to obtain rBMSCs, which were cultured and passaged in vitro. GFP was transfected into the third passage rBMSCs via adenovirus vector and the labeled cells were inoculated into absorbable HA scaffold and cultured for 3 days, with untransfected rBMSCs as control, before the cell-matrix compounds were implanted into the latissimus dorsi muscles of rhesus. Samples were harvested at 6 week and embedded in paraform, and ground sections of the bone tissue were prepared to observe green fluorescence under laser scanning confocal microscope. Propidium iodide staining of the sections was also performed for observation. RESULTS: The rBMSCs grew well after GFP transfection, and green fluorescence could be seen 24 h after the transfection and became stronger till 48 h, with a positive transfection rate beyond 80%. Six weeks after cell implantation, the rBMSCs labeled by GFP-emitted green fluorescence were detected in the bone tissue under laser scanning confocal microscope. CONCLUSION: GFP can effectively trace BMSCs during bone tissue engineering, and the transplanted BMSCs constitute the main source of bone forming cells in bone tissue engineering. PMID- 17355925 TI - [Evaluation of the questionnaire for subhealth status survey based on the symptoms in traditional Chinese medicine]. AB - OBJECTIVE: To evaluate the reliability and validity of the questionnaire we designed for subhealth status survey based on the symptoms described in traditional Chinese medicine. METHOD: By on-the-spot investigation, the recovery rate of the questionnaires was 96.3% and the response rate of the items was 97.2%. RESULTS: Internal consistency reliability coefficient of the questionnaire was high (0.9274-0.9676), and each item was closely associated with its related factors (with Spearman coefficient mostly above 0.6 except for that for bodily symptoms in female). Factor loading was approximately consistent with the structure and content of the questionnaire. CONCLUSION: This subhealth status questionnaire can be reliable and effective. PMID- 17355926 TI - [Hematoporphyrin derivative-mediated photodynamic therapy for human nasopharyngeal carcinoma: a comparative study with CNE2 and C666-1 cell lines in vitro]. AB - OBJECTIVE: To investigate biological effect of hematoporphyrin derivative (HpD) photodynamic therapy (PDT) on in vitro cultured nasopharyngeal carcinoma (NPC) cell lines CNE2 and C666-1. METHODS: CNE2 and C666-1 cells cultured in vitro were incubated in a medium containing HpD at different concentrations (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 microg/ml) for 4 h followed by exposure to different light doses (2, 5, 10, and 20 J/cm2) using a diode laser at 630 nm with power density of 20 mW/cm2. After 24 h of incubation with HpD-PDT, the survival rate of CNE2 and C666-1 cells were analyzed by MTT assay. RESULTS: HpD-PDT produced effective killing of CNE2 and C666-1 cells cultured in vitro, and the killing effects were positively correlated with HpD concentration and the irradiation dose. Exposure of CNE2 and C666-1 cells to irradiation dose of 20 J/cm2 resulted in the IC50 of 0.7 and 1.2 microg/ml, respectively (P<0.01). With the same HpD concentration and irradiation dose, the survival rate of C666-1 cells, however, was significantly higher than that of CNE2 cells (P<0.05). CONCLUSION: HpD-PDT may result in effective killing of CNE2 and C666-1 cells cultured in vitro, although C666-1 cells are less sensitive to HpD-PDT than CNE2 cells. PMID- 17355927 TI - [Generation of transgenic mice by intratesticular injection and electroporation in vivo]. AB - OBJECTIVE: To evaluate the feasibility of establishing transgenic mice by means of seminiferous tubule microinjection and electroporation (EP) in vivo. METHODS: Specific pathogen-free (SPF) male Kunming mice divided into 4 groups were subjected to microinjection of two different transfection solutions labeled with enhance green fluorescent protein (EGFP) into the seminiferous tubule of the testis, and in one of the two groups receiving the identical transfection solutions, EP in vivo was performed. After two weeks, the male mice of each group were mated with SPF female Kunming mice with superovulation treatment, and PCR coupled with Southern blotting was performed for the offspring mice. RESULTS: The results of PCR suggested significant difference in the efficiency of exogenous gene integration between the 4 groups (P<0.01), among which group A achieved the greatest efficiency (45%). Southern blotting did not identify significant difference between the 4 groups (P>0.05), but still suggested the highest efficiency in group A (25%). CONCLUSION: Seminiferous tubule microinjection in conjunction with subsequent EP in vivo can remarkably enhance the integration efficiency of exogenous genes into the host genome, but this new method needs to be further tested for its potential utility in transgenic animal generation. PMID- 17355928 TI - [Pharmacokinetics of amikacin in the subeschar tissue fluid following severe burns]. AB - OBJECTIVE: To investigate the changes of pharmacokinetic parameters of amikacin in the subeschar tissue fluid (STF) in the early stage of severe burns. METHODS: Amikacin concentration in the STF of 10 severely burned patients were determined by fluorescence polarization immunoassay (FPIA) at different time points after intravenous amikacin infusion of the initial dose of 400 mg given within 60 min. The pharmacokinetic parameters of amikacin were measured using 3P97 program and statistically analyzed with SPSS10.0 software. RESULTS AND CONCLUSION: After the initial dose of 400 mg of amikacin, the STF concentration-time curves of amikacin were fitted in two compartment model. The pharmacokinetic parameters of amikacin in the STF were: t(1/2alpha)=(4.35-/+1.66) h, t(1/2beta)= (80.04-/+9.52) h, Vc= (13.17-/+1.32) L, AUC= (1802.49-/+285.68) microg. h.ml(-1), and CLs= (0.2272 /+0.0383) L. h(-1), demonstrating significantly lower clearance and longer elimination half life of amikacin in the STF following amikacin administration in early stage of severe burns. Elimination half-life of amikacin in the STF in severely burned patients was 28.20-44.78 times longer than that in the serum of normal volunteers, and the effective inhibitory concentration of amikacin could maintain for at least 24 h, suggesting antibiotic retention in the third space after early and short-term use of potent antibiotics and formation of antibiotic barrier in the STF, which may help prevent bacterial infection of the wound. PMID- 17355929 TI - [Modification of vascular endothelial cell treatment for patch clamp study]. AB - A modified protocol for quick and economic treatment of cultured human umbilical vein endothelial cells has been established, which result in high viability of the cells to allow better performance in patch-clamp studies. The electrophysiological properties of Ca (2+)-activated K(+) (KCa) channel of the cultured cells were investigated with a cell-attached configuration. With this modified treatment method, the cultured cells appear fusiform in shape under microscope, and KCa channel currents could be detected readily, suggesting their eligibility for patch-clamp studies. PMID- 17355930 TI - [Synthesis of S-(+)-rivastigmine hydrogentartrate]. AB - OBJECTIVE: To optimize the synthetic procedure of S-(+)-rivastigmine hydrogentartrate which was known as an agent for the treatment of Alzheimer disease. METHODS: S-(+)-rivastigmine hydrogentartrate was synthesized by using 1 (3-hydroxyphenyl)ethanone as the starting material via oximation, reduction and N methylation to produce the key intermediate 3-1-dimethylaminoethylphenol, which finally reacted with N-ethyl-N-methylcarbamoyl chloride. The enantiomers were resolved with di-(+)-p-toluoyl-D-tartaric acid, and the title compound was prepared by mixing S-rivastigmine base with L-(+)-tartrate. RESULTS: The total yield of S-(+)-rivastigmine hydrogentartrate was 4.17%. CONCLUSION: The materials in this procedure are all commercially available. The reaction conditions are mild and total yield is high. PMID- 17355931 TI - [Magnetic resonance imaging findings of liver injury induced by three-dimensional conformal radiotherapy]. AB - OBJECTIVE: To analyze the magnetic resonance imaging (MRI) findings of radiation induced liver injury following three-dimensional conformal radiotherapy. METHODS: A retrospective review of the MRI data was conducted in 20 patients treated between September 2000 and October 2005, who suffered liver injuries induced by 1 or 2 three-dimensional conformal radiotherapy sessions for liver neoplasm. The patients underwent MR scans with T2-weighted sequences and T1-weighted sequences in both plain and Gd-DTPA enhanced MRI. Four patients with suspected tumor relapse suggested by MRI were pathologically confirmed to have radiation-induced liver injury. RESULTS: Acute radiation-induced liver injury was represented by large patches of liver edema consistent with the irradiation volume, showing low signal intensity on T1-weighted images (T1WI) and high signal intensity on T2 weighted images (T2WI) without arterial phase enhancement after Gd-DTPA injection. Delayed radiation-induced liver injury was manifested by slightly low intensity signal on plain T1WI and slightly high-intensity signal on T2WI without obvious arterial phase enhancement following Gd-DTPA injection but with marked enhancement during the portal-venous and delayed phases. CONCLUSION: Radiation induced liver injury presents characteristic MRI features, and plain and dynamic enhanced MRI can be of great value for its diagnosis. PMID- 17355932 TI - [Application of silk fibroin film for repairing rabbit urethral defect]. AB - OBJECTIVE: To evaluate the effect of silk fibroin film for repairing urethral defect in rabbits. METHODS: Twenty-four male New Zealand rabbits were randomized into experimental group, control group I and control group II. In the experimental group, a urethral defect of 1.5 cm was induced in the 12 rabbits and repaired with silk fibroin film. The 6 rabbits in control group I without the surgically induced defect served as the sham operation group, and in control group II consisting of 6 rabbits the urethral defect of 1.5 cm was induced without repair. Histological observation and immunohistochemistry were conducted to examine the regenerative segments of the urethra at regular time points between 2 and 16 weeks postoperatively. RESULTS: The 12 rabbits in the experimental group did not show signs of urethral stricture following the surgery. The implanted silk fibroin film for defect repair was degraded completely at 16 weeks and the defect was repaired with smooth urethral mucous membrane lining and orderly arranged smooth muscle cells. Immunohistochemistry identified the cells lining the defect area as the urethral epithelial cells. CONCLUSION: Silk fibroin film can promote the repair of urethral defect by inducing the growth of the urethral epithelial cells and smooth muscle cells. PMID- 17355933 TI - [Saponin from Tupistra chinensis Baker inhibits mouse sarcoma S-180 cell proliferation in vitro and implanted solid tumor growth in mice]. AB - OBJECTIVE: To study the antitumor effect of saponin extracted from Tupistra chinensis Baker (STCB) against mouse sarcoma S-180 cell proliferation in vitro and in vivo and explore the primary mechanism of this effect. METHODS: Cytotoxic effect of STCB on S-180 cells in vitro was evaluated by MTT colorimetry, and its effect against in vitro tumor growth was tested in Kunmin mice bearing S-180 implanted tumor. The morphological and ultrastructural changes of S-180 cells after saponin treatment in vitro were examined with light and transmission electron microscope. Flow cytometry was performed to examine the cell cycle and apoptosis of S180 cells treated with different concentrations of STCB with propidium iodide staining. RESULTS: STCB could markedly inhibit S-180 cell proliferation in vitro with 50% inhibitory concentration of 34.64 microg/ml. STCB given by intragastric administration also significantly inhibited the growth of S 180 solid tumor, and the inhibition rate exceeded 30% at the dose of 0.5 g/kg, reaching 54.86% at 2 g/kg. Electron microscopy and flow cytometry revealed increased S180 tumor cell apoptotic rate with the increment of saponin concentration, along with increased percentage of cells in S phase and decreased cells in G(2)/M phase in response to 10 or 30 microg/ml STCB treatment. At the concentration of 60 microg/ml, however, STCB resulted in an opposite effect on the cell cycles, presumably due to its interference with mitosis at high concentrations. CONCLUSIONS: STCB inhibits the growth of S-180 cells both in vivo and in vitro possibly by inducing cell apoptosis and interfering with the cell cycle progression of the tumor cells. PMID- 17355934 TI - [Exploration of the alternative splicing variants of rat phospholipase C-gamma 1 pre-mRNA]. AB - OBJECTIVE: To explore the expression of phospholipase C-gamma 1 (PLC-gamma1) alternative splicing variants in rats. METHODS: According to the sequence of human PLCG1 splicing variant, specific primers for rat PLC-gamma1 were designed and synthesized. The rat RNA was reverse transcribed into cDNA, which was amplified using the specific primers, and the PCR products were sequenced and analyzed using BLAST and bioinformatics methods. Totally 21 rat tissue samples were examined, including the heart, liver, lung, kidney, eyeball, and brain obtained in 3 different embryonic stages, 7 different early postnatal stages, and in adulthood. RESULTS: The result did not show that rat PLC-gamma1 had the same splicing variant (PLC-gamma1a, NM_002660) as human does. CONCLUSIONS: The same splicing variant of PLC-gamma1 detectable in human may not exist in rats, and the pre-mRNA may undergo splicing resulting predominantly in PLC-gamma1b mRNA. Very likely, the alternative splicing site of rat PLC-gamma1 is not identical to that of human. PMID- 17355935 TI - [Expression of bcl-2 gene in EBV-transformed human gastric epithelial cell line GES-1]. AB - OBJECTIVE: To detect bcl-2 gene expression in Epstein-Barr virus (EBV)-infected human gastric epithelial cell line GES-1 for understanding the role of bcl-2 gene in the carcinogenesis of EBV-associated gastric carcinoma. METHODS: Akata 1061 cells producing recombined EBV carrying neomycin resistance gene (NEOr) was used to mediate the EBV infection of human gastric epithelial cell line GES-1 via close contact, with the empty plasmid pcDNA3-transfected GES-1 cells via lipofectamine method as a control. The EBV-infected and pcDNA3-transfected cells were cloned by limited dilution and the positive clones selected with G418. Immunocytochemical staining was performed to detect the expressions of EBNA1 and Bcl-2 protein. RESULTS: Bcl-2 protein expression was detected in EBV-infected cells but not in the control cells. CONCLUSION: EBV infection can increase Bcl-2 expression in gastric epithelial cells, and such cell transformation effect of EBV is related to the overexpression of bcl-2 gene. PMID- 17355936 TI - [Effect and mechanism of L-arginine therapy for fetal growth retardation due to pregnancy-induced hypertension]. AB - OBJECTIVE: To investigate the therapeutic effect of L-arginine (L-Arg) administration on fetus growth retardation (FGR) due to pregnancy-induced hypertension and explore its mechanism. METHODS: Sixty-eight pregnant women with pregnancy-induced hypertension and FGR were enrolled in this study, and 25 of them were given L-Arg in addition to routine therapy. Umbilical artery flow parameters and serum NO concentrations in maternal and umbilical blood were measured, and the therapeutic effects were evaluated according to neonatal birth weight. RESULTS: L-Arg therapy markedly decreased the systolic/diastolic value, pulse index and resistant index (P=0.000,0), while increased the fast blood velocity rate(P=0.000,0). NO contents in maternal and umbilical blood were 60.45 /+22.68 and 28.45-/+11.35 micromol/L in L-Arg group, respectively, significantly higher than those in routine treatment group (P=0.000,0 and 0.001,7, respectively) but lower than those in the control group (P=0.000,8 and 0.000,0, respectively). The neonatal birth weights were 2.9-/+0.3 kg in L-Arg group, significantly higher than that in routine treatment group (2.7-/+0.3 kg, P=0.006,8) and similar with that of the control group (3012.9-/+295.9 g, P=0.176,2). CONCLUSION: L-Arg promote intrauterine growth of the fetus by increasing NO production and improving the umbilical artery flow in pregnant women with pregnancy-induced hypertension and FGR. PMID- 17355937 TI - [Imaging features of primary bone lymphoma and its histopathology]. AB - OBJECTIVE: To study the imaging features of primary bone of the lymphoma PLB on X ray, CT and magnetic resonance imaging (MRI). METHODS: The data of 8 patients (6 males and 3 females, aged 9-60 years with a median age of 26.5 years) with pathologically confirmed PLB were retrospectively reviewed. Plain radiographs were obtained in all the 8 cases, CT scans performed in 5 and MRI examinations in 7. Four patients underwent X-ray, CT and MRI, two underwent CT and MRI, and one underwent X-ray and MRI. Surgical resection was performed in 7 cases and biopsy done in 2, and routine histopathological examination and immunohistochemistry were performed for all patients. RESULTS: The site of PLB focus was found in the pelvic bone in 4 cases, right frontal bone in 1 case, proximal femoral bone in 1 case, occipital clivus in 2 cases, and vertebral column in 1 case. Plain X-ray revealed in 4 cases roughly normal shape of the involved bone with stippled interior bone structure destruction; the other 4 cases presented with slight or moderate bone expansion with obvious signs of osteolysis. CT scans displayed areas of different sizes of osteolytic cortical and marrow cavity destruction with large soft tissue masses around the lesion. MRI found heterogeneous iso- to hyperintense signals in the lesions in the bone and soft-tissue masses on T2 weighted images but homogeneous isointense signals on T2-weighted images. The tumors were obviously enhanced after contrast-enhanced scans on CT and MRI. Histological examination identified B-cell lymphoma in 5 cases and T-cell lymphoma in 4 cases. CONCLUSION: PBL is characterized in imaging examinations by basically normal shape of the involved bones with possible bone expansion, obvious stippled osteolytic destruction, large soft-tissue mass around the lesion and obvious enhancement after contrast-enhanced scans. PMID- 17355938 TI - [Gene cloning, expression and purification of fusion protein epidermal growth factor-linker-trichosanthin]. AB - OBJECTIVE: To construct a recombinant expression vector of the fusion protein epidermal growth factor (EGF)-Linker-trichosanthin (TCS) and achieve its expression in E. coli to obtain purified EGF-linker-TCS fusion protein. METHODS: The gene fragments of EGF-linker were amplified by PCR and inserted into the expression plasmid PQE30-TCS, followed by transformation of the recombinant plasmid into E. coli M15 for expression of the fusion protein. Ni-FF column chromatography was utilized for purification of the expressed product. RESULTS: The recombinant plasmid PQE30-EGF-linker-TCS was stably and highly expressed in E. coli M15. The expressed product existed in the form of soluble protein accounting for about 40% of total cellular protein and reached a purity of above 95% after purification with Ni-FF column chromatography. CONCLUSION: The recombinant plasmid PQE30/EGF-linker-TCS has been successfully constructed, which provides a basis for further structural and functional study of EGF and TCS and their potential clinical application for cancer therapy. PMID- 17355939 TI - [P-JAK2 and P-STAT3 protein expression and cell apoptosis following focal cerebral ischemia-reperfusion injury in rats]. AB - OBJECTIVE: To investigate the changes in phosphorylated JAK2 and STAT3 protein expression of and cell apoptosis following focal cerebral ischemia-reperfusion injury in rats. METHODS: A rat models of focal cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion using modified filament method. Immunohistochemistry and Western blot analysis were used to detect the expression of P-JAK2 and P-STAT3 proteins, and TUNEL assay was employed to examine the cell apoptosis. RESULTS: P-JAK2 and P-STAT3 protein expression increased significantly after cerebral ischemia-reperfusion injury in rats. The immunoreactivity was prominent in the peripheral of the ischemic region and reached the peak level at 24 h of reperfusion, followed by slight decrement. The apoptotic cells increased obviously after cerebral ischemia-reperfusion injury, also reaching the peak level at 24 h of reperfusion. CONCLUSION: The expression of phosphorylated JAK2 and STAT3 may be involved in the ischemic cellular events including apoptosis. JAK2/STAT3 signaling pathway plays a role in the pathophysiological process of cerebral ischemia/reperfusion cell injury and repair. PMID- 17355940 TI - [Effects of Chinese Bushen Zhuanggu medicine on bone loss in female rats after simulated weightlessness]. AB - OBJECTIVE: To study the effect of Bushen Zhuanggu, the traditional Chinese medicine for reinforcing kidney and strengthening bone, on bone loss in female rats after simulated weightlessness. METHOD: Thirty-six female SD rats were randomly divided into 3 groups, namely normal control group (group A) and two groups of weightlessness simulated by tail suspension (groups B and C). Group C were treated with the Chinese medicine, while groups A and B were given the same dose of normal saline. The experiment lasted 28 days, and all rats were allowed to drink water freely. RESULTS: In the rats of group B, serum bone Gla protein (BGP), alkaline phosphatase (ALP), estradiol (E(2)) and P content and femur bone mineral content (BMD) were significantly lower than those in group A (P<0.01, P<0.05), whereas serum calcium concentration was markedly higher than that in group A (P<0.01). In rats of group C, serum BGP, ALP, E2 and P content and femur BMD were significantly higher than those in group B (P<0.01, P<0.05), but serum calcium concentration was markedly lower (P<0.01). CONCLUSION: This Chinese prescription can stimulate bone formation and reduce bone loss in female rats subjected to simulated weightlessness. PMID- 17355941 TI - [Matrine-induced gamma-globin synthesis in K562 cells]. AB - OBJECTIVE: To study the effects of matrine on gamma-globin synthesis in K562 cells in vitro. METHODS: Benzidine staining was used to study the dose- and time dependent effects of matrine on hemoglobin synthesis in K562 cells, and Western blotting was performed to determine the level of hemoglobin F(alpha(2)gamma(2)). RESULTS: Benzidine staining showed that K562 cells treated with matrine of 0.1 mg/ml had a positivity rate for benzidine (BZ%) of 15.67% at 96 h after the treatment, and Western blotting indicated increased synthesis of hemoglobin F. CONCLUSION: Matrine can induce gamma-globin synthesis and increase hemoglobin F level in K562 cells, the effect of which resembles that of sodium butyrate. PMID- 17355942 TI - [Association of Gly82Ser polymorphism of receptor for advanced glycation end products gene in a type 2 diabetic Chinese population]. AB - OBJECTIVE: To assess the distribution frequency of Gly82Ser polymorphism of receptor for advanced glycation end products (RAGR) gene and investigate its association with type 2 diabetic Chinese patients. METHODS: The allele frequencies and genotype distribution of Gly82Ser polymorphism of RAGE gene were compared in a case-control study of 194 type 2 diabetic and 546 non-diabetic subjects. PCR-restriction fragment length polymorphism (PCR-RFLP) was used for detection of the genotype variants. RESULTS: In general Chinese population and type 2 diabetic Chinese patients, the most frequent genotype and allele of RAGR gene Gly82Ser polymorphism were genotype GG and allele G, whose frequency distribution were significantly higher than those in other countries (P<0.01). No significantly difference in the genotype frequencies or allele frequencies of Gly82Ser polymorphism were found between the diabetic patients and non-diabetic subjects (P>0.05). CONCLUSION: Gly82Ser polymorphism of RAGE gene does not demonstrate any association with type 2 diabetes in Chinese patients, but high genotype and allele frequencies of Gly82Ser polymorphism occur in Chinese population and type 2 diabetic Chinese patients. PMID- 17355943 TI - [Cellular compatibility of type collagen I scaffold and human adipose-derived stem cells]. AB - OBJECTIVE: To study the cellular compatibility of type I collagen scaffold and human adipose-derived stem cells (ADSC(S)) in order to explore appropriate scaffold materials for adipose tissue engineering. METHODS: The morphology and function of the ADSC(S) were observed by inverted phase contrast microscope, scanning electron microscope and XTT assay when cocultured type I collagen scaffold with ADSC(S) in vitro. Cells adhesive rates were also calculated. RESULT: ADSC(S) were able to attach, grow and proliferate well on the scaffolds. CONCLUSION: collagen I scaffold exhibits excellent cellular compatibility and can be used as a vehicle for adipose tissue engineering. PMID- 17355944 TI - [Chemical constituents of the non-alkaloid fraction of Uncaria macrophylla]. AB - OBJECTIVE: To analyze the chemical constituents of the non-alkaloid fraction of Uncaria macrophylla. METHODS: The constituents were separated and purified by silica gel chromatography and recrystalization, and their structures were identified by infrared, mass and nuclear magnetic resonance spectrometry. RESULTS: Six compounds were isolated from the non-alkaloid fraction of Uncaria macrophylla, whose structures were identified as beta-sitosterol, beta daucosterol, ursolic acid, alpha-amyrin acetate, 3beta, 6beta, 23-trihydroxyurs 12-en-28-oic acid, 3beta-hydroxyurs-12-en-27, and 3beta-hydroxyurs-12-en-27, 28 dioic acid, respectively. CONCLUSIONS: Ursolic acid is the main component in the non-alkaloid fraction of Uncaria macrophylla. Alpha-amyrin acetate and 3beta hydroxyurs-12-en-27, 28-dioic acid are isolated and characterized for the first time from this plant. PMID- 17355945 TI - [Lysophosphatidic acid promotes transplanted tumor growth of human epithelium ovarian cancer in nude mice]. AB - OBJECTIVE: To investigate effect of lysophosphatidic acid (LPA) on growth and metastasis of intraperitonally transplanted tumor in nude mice. METHODS: Sixteen nude mice randomly divided into control group and LPA treatment group, in which 6x10(6) untreated and LPA-treated human ovarian cancer cells skov3 were respectively transplanted intraperitoneally. After death of the nude mice without interventions, the weight of the transplanted tumors and number of metastatic tumors were recorded. RESULTS: The rate of tumor formation was 100%in both groups, but the treatment group showed more rapid tumor growth, greater tumor weight and more numerous metastatic tumors than the control group (P<0.01). CONCLUSION: LPA simulates the growth and promotes invasiveness of transplanted ovarian cancer cells in the peritoneal cavity of nude mie. PMID- 17355946 TI - 3,4-dichloropropionaniline suppresses normal macrophage function. AB - Macrophages are a critical part of the innate immune response and natural surveillance mechanisms. As such, proper macrophage function is crucial for engulfing bacterial pathogens through phagocytosis and destroying them by generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The production of a number of cytokines by macrophages, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, plays an important role in the initiation of the acquired immune response creating an inflammatory environment favorable for fighting a bacterial infection. 3,4 Dichloropropionaniline (DCPA) suppresses several inflammatory parameters, including TNF-alpha production through a mechanism where nuclear factor-kappaB (NF-kappaB)-DNA binding is inhibited but not entirely abrogated. The goal of the present study was to evaluate the effects of DCPA on the inflammatory mediators of macrophages, including ROS and RNS in both murine peritoneal exudate cells and the human monocytic cell line, THP-1. The ability to perform phagocytosis and directly kill Listeria monocytogenes was also assessed. The results indicate that DCPA decreases the ability of both types of macrophages to phagocytize beads and generate both types of reactive species, which was correlated with a decrement in listericidal activity. These results demonstrate that DCPA has profound effects on macrophage function and provide insight into the potential mechanisms of immunosuppression by DCPA. PMID- 17355947 TI - The glycine decarboxylase complex multienzyme family in Populus. AB - In plants, the glycine decarboxylase complex (GDC) cooperates with serine hydroxymethyltransferase (SHMT) to mediate photorespiratory glycine-serine interconversion. GDC is also postulated to be an integral component of one-carbon (C1) metabolism in heterotrophic tissues, although molecular evidence in plants is scarce. An initial report of a xylem-specific isoform of GDC component H protein, PtgdcH1, in aspen (Populus tremuloides Michx.) provided molecular evidence consistent with an important role for GDC in plant C1 metabolism. PtgdcH1 is phylogenetically distinct from the leaf-abundant photorespiratory PtgdcH3, but both isoforms restored GDC activity in a yeast H-protein knockout mutant, suggesting their functional equivalence. The Populus genome contains eight transcriptionally active GDC genes, encoding four H-proteins, two T proteins, and single P- and L-proteins. The two Populus T-protein isoforms, PtgdcT1 and PtgdcT2, exhibited differential expression in leaves and xylem, similar to PtgdcH3 and PtgdcH1. In silico identification of AC elements in the promoters of xylem-abundant PtgdcH1 and PtgdcT2, as well as many lignin biosynthetic genes of Populus is consistent with a prominent role for GDC in methyl-intensive lignification during wood formation. The AC element is absent from Arabidopsis GDC promoters, and GDC expression has not been linked to secondary growth in this herbaceous annual. Taken together, the results suggest that the association of distinct H-protein and T-protein isoforms with photorespiration and C1 metabolism is a distinguishing feature of Populus, and may signify molecular adaptation of GDC to cope with the C1 demands of lignification in woody perennials. PMID- 17355948 TI - Vacuolar calcium channels. AB - The central vacuole is the largest Ca2+ store in a mature plant cell. Ca2+ release from this store contributes to Ca2+-mediated intracellular signalling in a variety of physiological responses. However, the routes for vacuolar Ca2+ release are not well characterized. To date, at least two voltage-dependent and two ligand-gated Ca2+-permeable channels have been reported in plant vacuoles. However, the so-called VVCa (vacuolar voltage-gated Ca2+) channel most probably is not a separate channel but is identical to another voltage-dependent channel the so-called SV (slow vacuolar) channel. Studies in the last few years have added a new dimension to our knowledge of SV channel-mediated ion transport and the mechanisms of its regulation by multiple natural factors. Recently, the SV channel was identified as the product of the TPC1 gene in Arabidopsis. In contrast, the TPC1 channel from other species was thought to be localized in the plasma membrane. A re-evaluation of this work under the assumption that the TPC1 channel is generally a vacuolar channel provides interesting insights into the physiological function of the TPC1/SV channel. Considerably less is known about vacuolar Ca2+ channels that are supposed to be activated by inositol 1,4,5 trisphosphate or cADP ribose. The major problems are controversial reports about functional characteristics, and a remarkable lack of homologues of animal ligand gated Ca2+ channels in higher plants. To help understand Ca2+-mediated intracellular signalling in plant cells, a critical update of existing experimental evidence for vacuolar Ca2+ channels is presented. PMID- 17355949 TI - The treatment of lymphoma complicating autoimmune disease: two birds with one stone? PMID- 17355950 TI - Immunohistochemichal expression of biomarkers: a comparative study between diagnostic bronchial biopsies and surgical specimens of non-small-cell lung cancer. AB - BACKGROUND: The increasing use of biomarkers as molecular determinants of responsiveness to conventional chemotherapy or molecular targeted therapy has raised the question of the reliability and reproducibility of their evaluation in bronchial biopsies as compared with corresponding resected surgical specimens. PATIENTS AND METHODS: Immunohistochemical expression of five markers related to signal transduction [epidermal growth factor receptor (EGFR), phospho-Akt], cell proliferation (Ki-67), DNA repair [excision repair cross-complementing (ERCC)1] and cellular 'immortality' [human telomerase catalytic component (hTERT)], was assessed in 41 patients with operable non-small-cell lung cancer in both bronchial biopsies and whole surgical specimens. RESULTS: High correlation coefficients were observed between the expression of ERCC1, hTERT and Ki-67 in the biopsies and the surgical specimens [0.83 (P < 0.0001); 0.55 (P < 0.001) and 0.64 (P < 0.0001), respectively]. On the other hand, biomarker expression in biopsy was less correlated with the expression in the whole tissue sample for the markers of signal response and transduction [0.24 (P = 0.17) and 0.29 (P = 0.09) for EGFR and phospho-Akt, respectively]. CONCLUSIONS: Our results indicate a lack of association in the expression of important biomarkers between lung biopsies and corresponding resected tumors, with discordance rates ranging between 9% and 41%. Although these results need to be further validated in larger cohorts, they indicate that the evaluation of the expression of biomarkers in bronchial biopsies can be misleading. PMID- 17355951 TI - Interplay of distinct growth factors during epithelial mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies. AB - In this review, we describe the critical functions assumed by the interplay of epidermal growth factor, hedgehog, Wnt/beta-catenin, tumor growth factor-beta and integrin signaling cascades in tumorigenic and migrating cancer progenitor cells and activated stromal cells during carcinogenesis. These growth factors provide an important role for the sustained growth and survival of tumorigenic cancer progenitor cells and their progeny by up-regulating numerous mitotic and antiapoptotic signaling cascades. Furthermore, these potent morphogens may cooperate for inducing the molecular events associated with the epithelial mesenchymal program in cancer cells including the alterations in epithelial cell shape and motility through the dissociation of intercellular adherens junctions. Of therapeutic interest, new strategies for the development of more effective clinical treatments against the locally aggressive and invasive cancers based on the molecular targeting of deregulated signaling elements in tumorigenic and migrating cancer cells and their local microenvironment are also described. PMID- 17355952 TI - Feasibility and safety of autotransplants with noncryopreserved marrow or peripheral blood stem cells: a systematic review. AB - The objective of this systematic review is to examine the feasibility and safety of autologous noncryopreserved stem-cell transplants. This technique avoids the cost of establishing and maintaining a cryopreservation facility and may be of value for transplant centers in regions with limited economic resources. The primary outcome was the graft failure rate. In addition, a detailed description of the high-dose therapy regimens employed was undertaken. Secondary outcomes were transplant-related mortality and neutrophil and platelet engraftments times. Sixteen well-conducted nonrandomized studies met the eligibility criteria. Only two cases of graft failure (0.36%) occurred among 560 assessable patients receiving high-dose therapy and autotransplant for non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, germ-cell tumors and acute leukemias. The most traditional high-dose schedules were used, although often modified to shorter regimens. High-dose melphalan appeared especially useful given its short half-life and was used to treat multiple myeloma by most groups. Secondary outcomes were comparable to those reported in the most relevant studies addressing standard (cryopreserved) autotransplant. According to this study, the use of autologous noncryopreserved hematopoietic progenitors to support patients undergoing high-dose therapy is feasible and safe. PMID- 17355953 TI - Good death in cancer care: a nationwide quantitative study. AB - BACKGROUND: The aims of this study were to (i) conceptualize dimensions of a good death in Japanese cancer care, (ii) clarify the relative importance of each component of a good death and (iii) explore factors related to an individual's perception of the domains of a good death. METHODS: The general population was sampled using a stratified random sampling method (n = 2548; response rate, 51%) and bereaved families from 12 certified palliative care units were surveyed as well (n = 513; 70%). We asked the subjects about the relative importance of 57 components of a good death. RESULTS: Explanatory factor analysis demonstrated 18 domains contributing to a good death. Ten domains were classified as 'consistently important domains', including 'physical and psychological comfort', 'dying in a favorite place', 'good relationship with medical staff', 'maintaining hope and pleasure', 'not being a burden to others', 'good relationship with family', 'physical and cognitive control', 'environmental comfort', 'being respected as an individual' and 'life completion'. CONCLUSIONS: We quantitatively identified 18 important domains that contribute to a good death in Japanese cancer care. The next step of our work should be to conduct a national survey to identify what is required to achieve a good death. PMID- 17355954 TI - Hematopoietic cell transplantation: progress and obstacles. AB - The use of hematopoietic cell transplantation has expanded and evolved substantially in the last decade. New stem cell sources and stem cell mobilizing agents have been introduced in clinical practice. The incidence of life threatening complications following autologous stem cell transplant procedures has decreased dramatically. Understanding the immune mediated effect of allogeneic stem cell transplantation has resulted in the development of reduced intensity and non-myeloablative conditioning regimens, allowing transplantation of elderly patients. Long-term complications are starting to emerge, and will gain in importance in the near future. PMID- 17355955 TI - Prevalence of pain in patients with cancer: a systematic review of the past 40 years. AB - BACKGROUND: Despite the abundant literature on this topic, accurate prevalence estimates of pain in cancer patients are not available. We investigated the prevalence of pain in cancer patients according to the different disease stages and types of cancer. PATIENTS AND METHODS: A systematic review of the literature was conducted. An instrument especially designed for judging prevalence studies on their methodological quality was used. Methodologically acceptable articles were used in the meta-analyses. RESULTS: Fifty-two studies were used in the meta analysis. Pooled prevalence rates of pain were calculated for four subgroups: (i) studies including patients after curative treatment, 33% [95% confidence interval (CI) 21% to 46%]; (ii) studies including patients under anticancer treatment: 59% (CI 44% to 73%); (iii) studies including patients characterised as advanced/metastatic/terminal disease, 64% (CI 58% to 69%) and (iii) studies including patients at all disease stages, 53% (CI 43% to 63%). Of the patients with pain more than one-third graded their pain as moderate or severe. Pooled prevalence of pain was >50% in all cancer types with the highest prevalence in head/neck cancer patients (70%; 95% CI 51% to 88%). CONCLUSION: Despite the clear World Health Organisation recommendations, cancer pain still is a major problem. PMID- 17355956 TI - A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours. AB - BACKGROUND: The outcome of patients with germ-cell tumours (GCTs), who relapse more than once or relapse with a mediastinal primary is poor. We have shown that topoisomerase 1 may be an attractive target in relapsed GCT. We investigated the role of irinotecan, paclitaxel and oxaliplatin (IPO) followed by topotecan-based high-dose therapy in responding patients, in this patient population. PATIENTS AND METHODS: Twenty-eight patients with multiply relapsed gonadal and mediastinal GCT were recruited to this phase 2 study. All patients received IPO chemotherapy and 12 (43%) went on to receive high-dose therapy. The outcome of these patients was assessed using the Kaplan-Meier method with a median progression-free follow up of 1 year. RESULTS: Twenty patients (71%) responded to the therapy including five complete remissions (18%), 13 (46%) marker-negative partial responses and two (7%) marker-positive partial responses. Nine (32%) patients continue to be progression free, and the median survival for the whole group currently measures 17 months. Out of 12 individuals who received subsequent high-dose therapy consolidation, seven (58%) remain progression free. The commonest grade III/IV toxicity was infection (68%) and there were no IPO-related toxic deaths; there was one death from high-dose therapy. CONCLUSION: Topoisomerase I-based IPO chemotherapy that lacks etoposide is very active in multiply relapsed GCT. This data merit further investigation. PMID- 17355957 TI - ZnT5 variant B is a bidirectional zinc transporter and mediates zinc uptake in human intestinal Caco-2 cells. AB - Zinc is an essential micronutrient, so it is important to elucidate the molecular mechanisms of zinc homeostasis, including the functional properties of zinc transporters. Mammalian zinc transporters are classified in two major families: the SLC30 (ZnT) family and the SLC39 family. The prevailing view is that SLC30 family transporters function to reduce cytosolic zinc concentration, either through efflux across the plasma membrane or through sequestration in intracellular compartments, and that SLC39 family transporters function in the opposite direction to increase cytosolic zinc concentration. We demonstrated that human ZnT5 variant B (ZnT5B (hZTL1)), an isoform expressed at the plasma membrane, operates in both the uptake and the efflux directions when expressed in Xenopus laevis oocytes. We measured increased activity of the zinc-responsive metallothionein 2a (MT2a) promoter when ZnT5b was co-expressed with an MT2a promoter-reporter plasmid construct in human intestinal Caco-2 cells, indicating increased total intracellular zinc concentration. Increased cytoplasmic zinc concentration mediated by ZnT5B, in the absence of effects on intracellular zinc sequestration by the Golgi apparatus or endoplasmic reticulum, was also confirmed by a dramatically enhanced signal from the zinc fluorophore Rhodzin-3 throughout the cytoplasm of Caco-2 cells overexpressing ZnT5B at the plasma membrane when compared with control cells. Our findings demonstrate clearly that, in addition to mediating zinc efflux, ZnT5B at the plasma membrane can function to increase cytoplasmic zinc concentration, thus indicating a need to reevaluate the current paradigm that SLC30 family zinc transporters operate exclusively to decrease cytosolic zinc concentration. PMID- 17355958 TI - Oxidation and S-nitrosylation of cysteines in human cytosolic and mitochondrial glutaredoxins: effects on structure and activity. AB - Glutathione (GSH) is the major intracellular thiol present in 1-10-mm concentrations in human cells. However, the redox potential of the 2GSH/GSSG (glutathione disulfide) couple in cells varies in association with proliferation, differentiation, or apoptosis from -260 mV to -200 or -170 mV. Hydrogen peroxide is transiently produced as second messenger in receptor-mediated growth factor signaling. To understand oxidation mechanisms by GSSG or nitric oxide-related nitrosylation we studied effects on glutaredoxins (Grx), which catalyze GSH dependent thiol-disulfide redox reactions, particularly reversible glutathionylation of protein sulfhydryl groups. Human Grx1 and Grx2 contain Cys Pro-Tyr-Cys and Cys-Ser-Tyr-Cys active sites and have three and two additional structural Cys residues, respectively. We analyzed the redox state and disulfide pairing of Cys residues upon GSSG oxidation and S-nitrosylation. Cytosolic/nuclear Grx1 was partly inactivated by both S-nitrosylation and oxidation. Inhibition by nitrosylation was reversible under anaerobic conditions; aerobically it was stronger and irreversible, indicating inactivation by nitration. Oxidation of Grx1 induced a complex pattern of disulfide-bonded dimers and oligomers formed between Cys-8 and either Cys-79 or Cys-83. In addition, an intramolecular disulfide between Cys-79 and Cys-83 was identified, predicted to have a profound effect on the three-dimensional structure. In contrast, mitochondrial Grx2 retains activity upon oxidation, did not form disulfide-bonded dimers or oligomers, and could not be S-nitrosylated. The dimeric iron sulfur cluster-coordinating inactive form of Grx2 dissociated upon nitrosylation, leading to activation of the protein. The striking differences between Grx1 and Grx2 reflect their diverse regulatory functions in vivo and also adaptation to different subcellular localization. PMID- 17355959 TI - The signaling state of Arabidopsis cryptochrome 2 contains flavin semiquinone. AB - Cryptochrome (Cry) photoreceptors share high sequence and structural similarity with DNA repair enzyme DNA-photolyase and carry the same flavin cofactor. Accordingly, DNA-photolyase was considered a model system for the light activation process of cryptochromes. In line with this view were recent spectroscopic studies on cryptochromes of the CryDASH subfamily that showed photoreduction of the flavin adenine dinucleotide (FAD) cofactor to its fully reduced form. However, CryDASH members were recently shown to have photolyase activity for cyclobutane pyrimidine dimers in single-stranded DNA, which is absent for other members of the cryptochrome/photolyase family. Thus, CryDASH may have functions different from cryptochromes. The photocycle of other members of the cryptochrome family, such as Arabidopsis Cry1 and Cry2, which lack DNA repair activity but control photomorphogenesis and flowering time, remained elusive. Here we have shown that Arabidopsis Cry2 undergoes a photocycle in which semireduced flavin (FADH(.)) accumulates upon blue light irradiation. Green light irradiation of Cry2 causes a change in the equilibrium of flavin oxidation states and attenuates Cry2-controlled responses such as flowering. These results demonstrate that the active form of Cry2 contains FADH(.) (whereas catalytically active photolyase requires fully reduced flavin (FADH(-))) and suggest that cryptochromes could represent photoreceptors using flavin redox states for signaling differently from DNA-photolyase for photorepair. PMID- 17355960 TI - Solution NMR structure of the barrier-to-autointegration factor-Emerin complex. AB - The barrier-to-autointegration factor BAF binds to the LEM domain (Em(LEM)) of the nuclear envelope protein emerin and plays an essential role in the nuclear architecture of metazoan cells. In addition, the BAF(2) dimer bridges and compacts double-stranded DNA nonspecifically via two symmetry-related DNA binding sites. In this article we present biophysical and structural studies on a complex of BAF(2) and Em(LEM). Light scattering, analytical ultracentrifugation, and NMR indicate a stoichiometry of one molecule of Em(LEM) bound per BAF(2) dimer. The equilibrium dissociation constant (K(d)) for the interaction of the BAF(2) dimer and Em(LEM), determined by isothermal titration calorimetry, is 0.59 +/- 0.03 microm. Z-exchange spectroscopy between corresponding cross-peaks of the magnetically non-equivalent subunits of the BAF(2) dimer in the complex yields a dissociation rate constant of 78 +/- 2s(-1). The solution NMR structure of the BAF(2)-Em(LEM) complex reveals that the LEM and DNA binding sites on BAF(2) are non-overlapping and that both subunits of the BAF(2) dimer contribute approximately equally to the Em(LEM) binding site. The relevance of the implications of the structural and biophysical data on the complex in the context of the interaction between the BAF(2) dimer and Em(LEM) at the nuclear envelope is discussed. PMID- 17355961 TI - Structure of the dimeric exonuclease TREX1 in complex with DNA displays a proline rich binding site for WW Domains. AB - TREX1 is the most abundant mammalian 3' --> 5' DNA exonuclease. It has been described to form part of the SET complex and is responsible for the Aicardi Goutieres syndrome in humans. Here we show that the exonuclease activity is correlated to the binding preferences toward certain DNA sequences. In particular, we have found three motifs that are selected, GAG, ACA, and CTGC. To elucidate how the discrimination occurs, we determined the crystal structures of two murine TREX1 complexes, with a nucleotide product of the exonuclease reaction, and with a single-stranded DNA substrate. Using confocal microscopy, we observed TREX1 both in nuclear and cytoplasmic subcellular compartments. Remarkably, the presence of TREX1 in the nucleus requires the loss of a C terminal segment, which we named leucine-rich repeat 3. Furthermore, we detected the presence of a conserved proline-rich region on the surface of TREX1. This observation points to interactions with proline-binding domains. The potential interacting motif "PPPVPRPP" does not contain aromatic residues and thus resembles other sequences that select SH3 and/or Group 2 WW domains. By means of nuclear magnetic resonance titration experiments, we show that, indeed, a polyproline peptide derived from the murine TREX1 sequence interacted with the WW2 domain of the elongation transcription factor CA150. Co-immunoprecipitation studies confirmed this interaction with the full-length TREX1 protein, thereby suggesting that TREX1 participates in more functional complexes than previously thought. PMID- 17355962 TI - RUNX1-RUNX1 homodimerization modulates RUNX1 activity and function. AB - RUNX1 (AML1, CBFalpha2, PEBP2alphaB) is a transcription factor essential for the establishment of the hematopoietic stem cell. It is generally thought that RUNX1 exists as a monomer that regulates hematopoietic differentiation by interacting with tissue-specific factors and its DNA consensus through its N terminus. RUNX1 is frequently altered in human leukemia by gene fusions or point mutations. In general, these alterations do not affect the N terminus of the protein, and it is unclear how they consistently lead to hematopoietic transformation and leukemia. Here we report that RUNX1 homodimerizes through a mechanism involving C terminus C terminus interaction. This RUNX1-RUNX1 interaction regulates the activity of the protein in reporter gene assays and modulates its ability to induce hematopoietic differentiation of hematopoietic cell lines. The promoters of genes regulated by RUNX1 often contain multiple RUNX1 binding sites. This arrangement suggests that RUNX1 could homodimerize to bring and hold together distant chromatin sites and factors and that if the dimerization region is removed by gene fusions or is altered by point mutations, as observed in leukemia, the ability of RUNX1 to regulate differentiation could be impaired. PMID- 17355963 TI - Ca2+ signaling in microdomains: Homer1 mediates the interaction between RyR2 and Cav1.2 to regulate excitation-contraction coupling. AB - Excitation-contraction (E-C) coupling and Ca(2+)-induced Ca(2+) release in smooth and cardiac muscles is mediated by the L-type Ca(2+) channel isoform Ca(v)1.2 and the ryanodine receptor isoform RyR2. Although physical coupling between Ca(v)1.1 and RyR1 in skeletal muscle is well established, it is generally assumed that Ca(v)1.2 and RyR2 do not directly communicate either passively or dynamically during E-C coupling. In the present work, we re-examined this assumption by studying E-C coupling in the detrusor muscle of wild type and Homer1(-/-) mice and by demonstrating a Homer1-mediated dynamic interaction between Ca(v)1.2 and RyR2 using the split green fluorescent protein technique. Deletion of Homer1 in mice (but not of Homer2 or Homer3) resulted in impaired urinary bladder function, which was associated with higher sensitivity of the detrusor muscle to muscarinic stimulation and membrane depolarization. This was not due to an altered expression or function of RyR2 and Ca(v)1.2. Most notably, expression of Ca(v)1.2 and RyR2 tagged with the complementary C- and N-terminal halves of green fluorescent protein and in the presence and absence of Homer1 isoforms revealed that H1a and H1b/c reciprocally modulates a dynamic interaction between Ca(v)1.2 and RyR2 to regulate the intensity of Ca(2+)-induced Ca(2+) release and its dependence on membrane depolarization. These findings define the molecular basis of a "two-state" model of E-C coupling by Ca(v)1.2 and RyR2. In one state, Ca(v)1.2 couples to RyR2 by H1b/c, which results in reduced responsiveness to membrane depolarization and in the other state H1a uncouples Ca(v)1.2 and RyR2 to enhance responsiveness to membrane depolarization. These findings reveal an unexpected and novel mode of interaction and communication between Ca(v)1.2 and RyR2 with important implications for the regulation of smooth and possibly cardiac muscle E-C coupling. PMID- 17355964 TI - Role of the H domain of the histidine kinase-like protein NifL in signal transmission. AB - The NifL protein from Azotobacter vinelandii senses both the redox and fixed nitrogen status to regulate nitrogen fixation by controlling the activity of the transcriptional activator NifA. NifL has a domain architecture similar to that of the cytoplasmic histidine protein kinases. It contains two N-terminal PAS domains and a C-terminal transmitter region containing a conserved histidine residue (H domain) and a nucleotide binding GHKL domain corresponding to the catalytic core of the histidine kinases. Despite these similarities, NifL does not exhibit kinase activity and regulates its partner NifA by direct protein-protein interactions rather than phosphorylation. NifL senses the redox status via a FAD co-factor located within the PAS1 domain and responds to the nitrogen status by interaction with the signal transduction protein GlnK, which binds to the GHKL domain. The ability of NifL to inhibit NifA is antagonized by the binding of 2 oxoglutarate to the N-terminal GAF domain of NifA. In this study we have performed site-directed mutagenesis of the H domain of NifL to examine its role in signal transmission. Our results suggest that this domain plays a major role in transmission of signals perceived by the PAS1 and GHKL domains to ensure that NifL achieves the required conformation necessary to inhibit the 2-oxoglutarate bound form of NifA. Some of the substitutions discriminate the redox and fixed nitrogen sensing functions of NifL implying that the conformational requirements and/or domain interactions necessary for NifA inhibition differ with respect to the signal input. PMID- 17355965 TI - Mapping of the vitronectin-binding site on the urokinase receptor: involvement of a coherent receptor interface consisting of residues from both domain I and the flanking interdomain linker region. AB - The urokinase-type plasminogen activator receptor (uPAR) has been implicated as a modulator of several biochemical processes that are active during tumor invasion and metastasis, e.g. extracellular proteolysis, cell adhesion, and cell motility. The structural basis for the high affinity interaction between the urokinase-type plasminogen activator (uPA) and uPAR, which focuses cell surface-associated plasminogen activation in vivo, is now thoroughly characterized by site-directed mutagenesis studies and x-ray crystallography. In contrast, the structural basis for the interaction between uPAR and the extracellular matrix protein vitronectin, which is involved in the regulation of cell adhesion and motility, remains to be clarified. In this study, we have identified the functional epitope on uPAR that is responsible for its interaction with the full-length, extended form of vitronectin by using a comprehensive alanine-scanning library of purified single-site uPAR mutants (244 positions tested). Interestingly, the five residues identified as "hot spots" for vitronectin binding form a contiguous epitope consisting of two exposed loops connecting the central fourstranded beta-sheet in uPAR domain I (Trp(32), Arg(58), and Ile(63)) as well as a proximal region of the flexible linker peptide connecting uPAR domains I and II (Arg(91) and Tyr(92)). This binding topology provides the molecular basis for the observation that uPAR can form a ternary complex with uPA and vitronectin. Furthermore, it raises the intriguing possibility that the canonical receptor and inhibitor for uPA (uPAR and PAI-1) may have reached a convergent solution for binding to the somatomedin B domain of vitronectin. PMID- 17355966 TI - Identification and characterization of the human Set1B histone H3-Lys4 methyltransferase complex. AB - We previously identified a mammalian Set1A complex analogous to the yeast Set1/COMPASS histone H3-Lys4 methyltransferase complex (Lee, J.-H., and Skalnik, D. G. (2005) J. Biol. Chem. 280, 41725-41731). Data base analysis indicates that human Set1A protein shares 39% identity with an uncharacterized SET domain protein, KIAA1076, hereafter denoted Set1B. Immunoprecipitation and mass spectrometry reveal that Set1B associates with a approximately 450 kDa complex that contains all five non-catalytic components of the Set1A complex, including CFP1, Rbbp5, Ash2, Wdr5, and Wdr82. These data reveal two human protein complexes that differ only in the identity of the catalytic histone methyltransferase. In vitro assays demonstrate that the Set1B complex is a histone methyltransferase that produces trimethylated histone H3 at Lys(4). Both Set1A and Set1B are widely expressed. Inducible expression of the carboxyl terminus of either Set1A or Set1B decreases steady-state levels of both endogenous Set1A and Set1B protein, but does not alter the expression of the non-catalytic components of the Set1 complexes. A 123-amino acid fragment upstream of the Set1A SET domain is necessary for interaction with CFP1, Ash2, Rbbp5, and Wdr5. This protein domain is also required to mediate feedback inhibition of Set1A and Set1B expression, which is a consequence of reduced Set1A and Set1B stability when not associated with the methyltransferase complex. Confocal microscopy reveals that Set1A and Set1B each localize to a largely non-overlapping set of euchromatic nuclear speckles, suggesting that Set1A and Set1B each bind to a unique set of target genes and thus make non-redundant contributions to the epigenetic control of chromatin structure and gene expression. PMID- 17355967 TI - Nucleic acids exert a sequence-independent cooperative effect on sequence dependent activation of Toll-like receptor 9. AB - Toll-like receptor 9 (TLR9) activates the innate immune system in response to microbial DNA or mimicking oligodeoxynucleotides. Although cell stimulation experiments demonstrate the preferential activation of TLR9 by CpG-containing nucleic acids, direct binding investigations have reached contradictory conclusions with respect to the ability of this receptor to bind nucleic acids in a sequence-specific manner. To address this apparent discrepancy, we report the purification of the soluble ectodomain of human TLR9 with characterization of its ligand binding properties. We observe that TLR9 has a high degree of specificity in its ability to bind nucleic acids that contain CpG dinucleotides as well as higher order motifs that mediate species-specific activation. However, TLR9 is also functionally influenced by nucleic acids in a sequence-independent fashion as both stimulatory and nonstimulatory nucleic acids sensitize TLR9 for in vitro ligand binding as well as in vivo activation. We propose a model in which receptor activation is achieved in a sequence-dependent manner, and sensitivity is modulated by the absolute concentration of nucleic acids in a sequence independent fashion. This model bears resemblance to that recently proposed for Toll in that activation is a two-step process in which formation of a ligand bound monomer precedes formation of the activated dimer. In each model receptor sensitivity is determined within the second step with the crucial distinction that Toll undergoes negative cooperativity, whereas TLR9 is sensitized through a positive cooperative effect. PMID- 17355968 TI - The NOD2-RICK complex signals from the plasma membrane. AB - NOD2 plays an important role in the innate immunity of the intestinal tract. By sensing the muramyl dipeptide (MDP), a bacterial wall component, NOD2 triggers the NF-kappaB signaling pathway and promotes the release of proinflammatory cytokines such as interleukin-8. Mutations in Nod2 (1007FS, R702W, G908R) impinge on NOD2 functions and are associated with the pathogenesis of Crohn disease, a chronic inflammatory bowel disease. Although NOD2 is usually described as a cytosolic receptor for MDP, the protein is also localized at the plasma membrane, and the 1007FS mutation delocalizes NOD2 to the cytoplasm (Barnich, N., Aguirre, J. E., Reinecker, H. C., Xavier, R., and Podolsky, D. K. (2005) J. Cell Biol. 170, 21-26; McDonald, C., Chen, F. F., Ollendorff, V., Ogura, Y., Marchetto, S., Lecine, P., Borg, J. P., and Nunez, G. (2005) J. Biol. Chem. 280, 40301-40309). In this study, we demonstrate that membrane-bound versions of NOD2 and Crohn disease-associated mutants R702W and G908R are capable of responding to MDP and activating the NF-kappaB pathway from this location. In contrast, the 1007FS mutant remains unable to respond to MDP from the plasma membrane. We also show that NOD2 promotes the membrane recruitment of RICK, a serine-threonine kinase involved in NF-kappaB activation downstream of NOD2. Furthermore, the artificial attachment of RICK at the plasma membrane provokes a constitutive and strong activation of the NF-kappaB pathway and secretion of interleukin-8 showing that optimal RICK activity depends upon its subcellular localization. Finally, we show that endogenous RICK localizes at the plasma membrane in the THP1 cell line. Thus, our data suggest that NOD2 is responsible for the membrane recruitment of RICK to induce a regulated NF-kappaB signaling and production of proinflammatory cytokines. PMID- 17355969 TI - Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. AB - IL-17F and IL-17A are members of the IL-17 pro-inflammatory cytokine family. IL 17A has been implicated in the pathogenesis of autoimmune diseases. IL-17F is a disulfide-linked dimer that contains a cysteine-knot motif. We hypothesized that IL-17F and IL-17A could form a heterodimer due to their sequence homology and overlapping pattern of expression. We evaluated the structure of recombinant IL 17F and IL-17A proteins, as well as that of natural IL-17F and IL-17A derived from activated human CD4+ T cells, by enzyme-linked immunosorbent assay, immunoprecipitation followed by Western blotting, and mass spectrometry. We find that both IL-17F and IL-17A can form both homodimeric and heterodimeric proteins when expressed in a recombinant system, and that all forms of the recombinant proteins have in vitro functional activity. Furthermore, we find that in addition to the homodimers of IL-17F and IL-17A, activated human CD4+ T cells also produce the IL-17F/IL-17A heterodimer. These data suggest that the IL-17F/IL-17A heterodimer may contribute to the T cell-mediated immune responses. PMID- 17355970 TI - Activation of a novel calcineurin-mediated insulin-like growth factor-1 receptor pathway, altered metabolism, and tumor cell invasion in cells subjected to mitochondrial respiratory stress. AB - We have previously shown that disruption of mitochondrial membrane potential by depletion of mitochondrial DNA (mtDNA) or treatment with a mitochondrial ionophore, carbonyl cyanide m-chlorophenylhydrazone, initiates a stress signaling, which causes resistance to apoptosis, and induces invasive behavior in C2C12 myocytes and A549 cells. In the present study we show that calcineurin (Cn), activated as part of this stress signaling, plays an important role in increased glucose uptake and glycolysis. Here we report that, although both insulin and insulin-like growth factor-1 receptor levels (IR and IGF1R, respectively) are increased in response to mitochondrial stress, autophosphorylation of IGF1R was selectively increased suggesting a shift in receptor pathways. Using an approach with FK506, an inhibitor of Cn, and mRNA silencing by small interference RNA we show that mitochondrial stress-activated Cn is critical for increased GLUT 4 and IGF1R expression and activation. The importance of the IGF1R pathway in cell survival under mitochondrial stress is demonstrated by increased apoptosis either by IGF1R mRNA silencing or by treatment with IGF1R inhibitors (AG1024 and picropodophyllin). This study describes a novel mechanism of mitochondrial stress-induced metabolic shift involving Cn with implications in resistance to apoptosis and tumor proliferation. PMID- 17355971 TI - A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. AB - The activation of spinal cord glial cells has been implicated in the development of neuropathic pain upon peripheral nerve injury. The molecular mechanisms underlying glial cell activation, however, have not been clearly elucidated. In this study, we found that damaged sensory neurons induce the expression of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and inducible nitric oxide synthase genes in spinal cord glial cells, which is implicated in the development of neuropathic pain. Studies using primary glial cells isolated from toll-like receptor 2 knock-out mice indicate that damaged sensory neurons activate glial cells via toll-like receptor 2. In addition, behavioral studies using toll-like receptor 2 knock-out mice demonstrate that the expression of toll like receptor 2 is required for the induction of mechanical allodynia and thermal hyperalgesia due to spinal nerve axotomy. The nerve injury-induced spinal cord microglia and astrocyte activation is reduced in the toll-like receptor 2 knock out mice. Similarly, the nerve injury-induced pro-inflammatory gene expression in the spinal cord is also reduced in the toll-like receptor 2 knock-out mice. These data demonstrate that toll-like receptor 2 contributes to the nerve injury induced spinal cord glial cell activation and subsequent pain hypersensitivity. PMID- 17355972 TI - MukE and MukF form two distinct high affinity complexes. AB - The MukBFE complex is essential for chromosome segregation and condensation in Escherichia coli. MukB is functionally related to the structural maintenance of chromosomes (SMC) proteins. Similar to SMCs, MukB requires accessory proteins (MukE and MukF) to form a functional complex for DNA segregation. MukF is a member of the kleisin family, which includes proteins that commonly mediate the interaction between SMCs and other accessory proteins, suggesting that the similarities between the MukBFE and the SMC complexes extend beyond MukB. Although SMCs have been carefully studied, little is known about the roles of their accessory components. In the present work, we characterize the oligomeric states of MukE and MukF using size exclusion chromatography and analytical ultracentrifugation. MukE self-associates to form dimers (K(D) 18 +/- 3 mum), which in turn interact with the MukF dimer to form two distinct high affinity complexes having 2:2 and 2:4 stoichiometries (F:E). Intermediate complexes are not found, and thus we propose that the equilibrium between these two complexes determines the formation of a functional MukBFE with stoichiometry 2:2:2. PMID- 17355973 TI - Structural organization of essential iron-sulfur clusters in the evolutionarily highly conserved ATP-binding cassette protein ABCE1. AB - The ABC protein ABCE1, formerly named RNase L inhibitor RLI1, is one of the most conserved proteins in evolution and is expressed in all organisms except eubacteria. Because of its fundamental role in translation initiation and/or ribosome biosynthesis, ABCE1 is essential for life. Its molecular mechanism has, however, not been elucidated. In addition to two ABC ATPase domains, ABCE1 contains a unique N-terminal region with eight conserved cysteines, predicted to coordinate iron-sulfur clusters. Here we present detailed information on the type and on the structural organization of the Fe-S clusters in ABCE1. Based on biophysical, biochemical, and yeast genetic analyses, ABCE1 harbors two essential diamagnetic [4Fe-4S](2+) clusters with different electronic environments, one ferredoxin-like (CPX(n)CX(2)CX(2)C; Cys at positions 4-7) and one unique ABCE1 type cluster (CXPX(2)CX(3)CX(n)CP; Cys at positions 1, 2, 3, and 8). Strikingly, only seven of the eight conserved cysteines coordinating the Fe-S clusters are essential for cell viability. Mutagenesis of the cysteine at position 6 yielded a functional ABCE1 with the ferredoxin-like Fe-S cluster in a paramagnetic [3Fe 4S](+) state. Notably, a lethal mutation of the cysteine at position 4 can be rescued by ligand swapping with an adjacent, extra cysteine conserved among all eukaryotes. PMID- 17355974 TI - Transcriptional up-regulation of inhibitory PAS domain protein gene expression by hypoxia-inducible factor 1 (HIF-1): a negative feedback regulatory circuit in HIF 1-mediated signaling in hypoxic cells. AB - The inhibitory PAS (Per/Arnt/Sim) domain protein (IPAS), a dominant negative regulator of hypoxia-inducible transcription factors (HIFs), is potentially implicated in negative regulation of angiogenesis in such tissues as the avascular cornea of the eye. We have previously shown IPAS mRNA expression is up regulated in hypoxic tissues, which at least in part involves hypoxia-dependent alternative splicing of the transcripts from the IPAS/HIF-3alpha locus. In the present study, we demonstrate that a hypoxia-driven transcriptional mechanism also plays a role in augmentation of IPAS gene expression. Isolation and analyses of the promoter region flanking to the first exon of IPAS gene revealed a functional hypoxia response element at position -834 to -799, whereas the sequence upstream of the HIF-3alpha first exon scarcely responded to hypoxic stimuli. A transient transfection experiment demonstrated that HIF-1alpha mediates IPAS promoter activation via the functional hypoxia response element under hypoxic conditions and that a constitutively active form of HIF-1alpha is sufficient for induction of the promoter in normoxic cells. Moreover, chromatin immunoprecipitation and electrophoretic mobility shift assays showed binding of the HIF-1 complex to the element in a hypoxia-dependent manner. Taken together, HIF-1 directly up-regulates IPAS gene expression through a mechanism distinct from RNA splicing, providing a further level of negative feedback gene regulation in adaptive responses to hypoxic/ischemic conditions. PMID- 17355975 TI - Inhibition of topoisomerase I cleavage activity by thiol-reactive compounds: importance of vicinal cysteines 504 and 505. AB - DNA topoisomerase I (Top1) is a nuclear enzyme that plays a crucial role in the removal of DNA supercoiling associated with replication and transcription. It is also the target of the anticancer agent, camptothecin (CPT). Top1 contains eight cysteines, including two vicinal residues (504 and 505), which are highly conserved across species. In this study, we show that thiol-reactive compounds such as N-ethylmaleimide and phenylarsine oxide can impair Top1 catalytic activity. We demonstrate that in contrast to CPT, which inhibits Top1-catalyzed religation, thiolation of Top1 inhibited the DNA cleavage step of the reaction. This inhibition was more pronounced when Top1 was preincubated with the thiol reactive compound and could be reversed in the presence of dithiothreitol. We also established that phenylarsine oxide-mediated inhibition of Top1 cleavage involved the two vicinal cysteines 504 and 505, as this effect was suppressed when cysteines were mutated to alanines. Interestingly, mutation of Cys-505 also altered Top1 sensitivity to CPT, even in the context of the double Cys-504 to Cys 505 mutant, which relaxed supercoiled DNA with a comparable efficiency to that of wild-type Top1. This indicates that cysteine 505, which is located in the lower Lip domain of human Top1, is critical for optimal poisoning of the enzyme by CPT and its analogs. Altogether, our results suggest that conserved vicinal cysteines 504 and 505 of human Top1 play a critical role in enzyme catalytic activity and are the target of thiol-reactive compounds, which may be developed as efficient Top1 catalytic inhibitors. PMID- 17355976 TI - Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation associated increase in 2-OH ceramides during keratinocyte differentiation. AB - Ceramides in mammalian stratum corneum comprise a heterogeneous mixture of molecular species that subserve the epidermal permeability barrier, an essential function for survival in a terrestrial environment. In addition to a variation of sphingol species, hydroxylation of the amide-linked fatty acids contributes to the diversity of epidermal ceramides. Fatty acid 2-hydroxylase, encoded by the gene FA2H, the mammalian homologue of FAH1 in yeast, catalyzes the synthesis of 2 hydroxy fatty acid-containing sphingolipids. We assessed here whether FA2H accounts for 2-hydroxyceramide/2-hydroxyglucosylceramide synthesis in epidermis. Reverse transcription-PCR and Western immunoblots demonstrated that FA2H is expressed in cultured human keratinocytes and human epidermis, with FA2H expression and fatty acid 2-hydroxylase activity increased with differentiation. FA2H-siRNA suppressed 2-hydroxylase activity and decreased 2-hydroxyceramide/2 hydroxyglucosylceramide levels, demonstrating that FA2H accounts for synthesis of these sphingolipids in keratinocytes. Whereas FA2H expression and 2-hydroxy free fatty acid production increased early in keratinocyte differentiation, production of 2-hydroxyceramides/2-hydroxyglucosylceramides with longer chain amide-linked fatty acids (> or =C24) increased later. Keratinocytes transduced with FA2H-siRNA contained abnormal epidermal lamellar bodies and did not form the normal extracellular lamellar membranes required for the epidermal permeability barrier. These results reveal that 1) differentiation-dependent up-regulation of ceramide synthesis and fatty acid elongation is accompanied by up-regulation of FA2H; 2) 2 hydroxylation of fatty acid by FA2H occurs prior to generation of ceramides/glucosylceramides; and 3) 2-hydroxyceramides/2-hydroxyglucosylceramides are required for epidermal lamellar membrane formation. Thus, late differentiation-linked increases in FA2H expression are essential for epidermal permeability barrier homeostasis. PMID- 17355977 TI - Coordination of steps in single-nucleotide base excision repair mediated by apurinic/apyrimidinic endonuclease 1 and DNA polymerase beta. AB - The individual steps in single-nucleotide base excision repair (SN-BER) are coordinated to enable efficient repair without accumulation of cytotoxic DNA intermediates. The DNA transactions and various proteins involved in SN-BER of abasic sites are well known in mammalian systems. Yet, despite a wealth of information on SN-BER, the mechanism of step-by-step coordination is poorly understood. In this study we conducted experiments toward understanding step-by step coordination during BER by comparing DNA binding specificities of two major human SN-BER enzymes, apurinic/aprymidinic endonuclease 1 (APE) and DNA polymerase beta (Pol beta). It is known that these enzymes do not form a stable complex in solution. For each enzyme, we found that DNA binding specificity appeared sufficient to explain the sequential processing of BER intermediates. In addition, however, we identified at higher enzyme concentrations a ternary complex of APE.Pol beta.DNA that formed specifically at BER intermediates containing a 5'-deoxyribose phosphate group. Formation of this ternary complex was associated with slightly stronger Pol beta gap-filling and much stronger 5' deoxyribose phosphate lyase activities than was observed with the Pol beta.DNA binary complex. These results indicate that step-by-step coordination in SN-BER can rely on DNA binding specificity inherent in APE and Pol beta, although coordination also may be facilitated by APE.Pol beta.DNA ternary complex formation with appropriate enzyme expression levels or enzyme recruitment to sites of repair. PMID- 17355978 TI - A putative Src homology 3 domain binding motif but not the C-terminal dystrophin WW domain binding motif is required for dystroglycan function in cellular polarity in Drosophila. AB - The conserved dystroglycan-dystrophin (Dg.Dys) complex connects the extracellular matrix to the cytoskeleton. In humans as well as Drosophila, perturbation of this complex results in muscular dystrophies and brain malformations and in some cases cellular polarity defects. However, the regulation of the Dg.Dys complex is poorly understood in any cell type. We now find that in loss-of-function and overexpression studies more than half (34 residues) of the Dg proline-rich conserved C-terminal regions can be truncated without significantly compromising its function in regulating cellular polarity in Drosophila. Notably, the truncation eliminates the WW domain binding motif at the very C terminus of the protein thought to mediate interactions with dystrophin, suggesting that a second, internal WW binding motif can also mediate this interaction. We confirm this hypothesis by using a sensitive fluorescence polarization assay to show that both WW domain binding sites of Dg bind to Dys in humans (K(d) = 7.6 and 81 microM, respectively) and Drosophila (K(d) = 16 and 46 microM, respectively). In contrast to the large deletion mentioned above, a single proline to an alanine point mutation within a predicted Src homology 3 domain (SH3) binding site abolishes Dg function in cellular polarity. This suggests that an SH3-containing protein, which has yet to be identified, functionally interacts with Dg. PMID- 17355979 TI - Cohort Profile: Mandela's children: the 1990 Birth to Twenty study in South Africa. PMID- 17355980 TI - Epidemiology: a science for justice in health. PMID- 17355981 TI - Disruptive innovation: can health care learn from other industries? A conversation with Clayton M. Christensen. Interview by Mark D. Smith. AB - Clayton Christensen is one of America's most influential business thinkers and writers. A professor at Harvard Business School, Christensen is perhaps best known for his writings on disruptive innovation in such books as The Innovator's Dilemma and The Innovator's Solution. In this interview with the California HealthCare Foundation's Mark Smith, he argues that the answer for more affordable health care will come not from an injection of more funding but, rather, from innovations that aim to make more and more areas of care cheaper, simpler, and more in the hands of patients. Christensen has been an adviser to several new companies in health care. PMID- 17355982 TI - MDA improvement technique for lung counter measurements of uranium workers. AB - A practical and simple method was employed to improve the minimum detectable activity (MDA) for lung counting measurements by summing several accumulated spectra. The method was checked for natural uranium, which produces peaks due to photon energies of 63.3, 92.6 and 185.7 keV. By combining nine measurements, an overall improvement of the MDA by a factor of about 3 was achieved. Uranium contamination levels lower than the MDA of a single spectrum could be detected with acceptable accuracy when analyzing the sum spectra. Specific results are given for four workers occupationally exposed to natural uranium. PMID- 17355983 TI - Improved localization of a 'hot spot' in the lungs for an array of four HPGe detectors--the isotopic ratio effect. AB - Considerable errors in the determination of radioactivity in lungs are caused by the usual assumption of homogeneous distribution, while actually the radioactive contamination can be distributed, and even in the form of a 'hot spot'. Modern lung counter systems use several HPGe detectors, and the ratio of the different count rates of the detectors can be used to locate a 'hot spot' and apply correction algorithms for activity calculation. In the present work it is shown that the variability of the isotopic composition of the uranium source has a major effect on the process of localization of the 'hot spot' in the lungs. A way to eliminate this effect is proposed by separate normalization of the count rates of each energy peak. PMID- 17355984 TI - Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells. AB - The nucleolus is the site of ribosome synthesis in the nucleus, whose integrity is essential. Epigenetic mechanisms are thought to regulate the activity of the ribosomal RNA (rRNA) gene copies, which are part of the nucleolus. Here we show that human cells lacking DNA methyltransferase 1 (Dnmt1), but not Dnmt33b, have a loss of DNA methylation and an increase in the acetylation level of lysine 16 histone H4 at the rRNA genes. Interestingly, we observed that SirT1, a NAD+ dependent histone deacetylase with a preference for lysine 16 H4, interacts with Dnmt1; and SirT1 recruitment to the rRNA genes is abrogated in Dnmt1 knockout cells. The DNA methylation and chromatin changes at ribosomal DNA observed are associated with a structurally disorganized nucleolus, which is fragmented into small nuclear masses. Prominent nucleolar proteins, such as Fibrillarin and Ki 67, and the rRNA genes are scattered throughout the nucleus in Dnmt1 deficient cells. These findings suggest a role for Dnmt1 as an epigenetic caretaker for the maintenance of nucleolar structure. PMID- 17355985 TI - Transactivation of a DR-1 PPRE by a human constitutive androstane receptor variant expressed from internal protein translation start sites. AB - Downstream in-frame start codons produce amino-terminal-truncated human constitutive androstane receptor protein isoforms (DeltaNCARs). The DeltaNCARs are expressed in liver and in vitro cell systems following translation from in frame methionine AUG start codons at positions 76, 80, 125, 128, 168 and 265 within the full-length CAR mRNA. The resulting CAR proteins lack the N-terminal DNA-binding domain (DBD) of the receptor, yielding DeltaNCAR variants with unique biological function. Although the DeltaNCARs maintain full retinoid X receptor alpha (RXRalpha) heterodimerization capacity, the DeltaNCARs are inactive on classical CAR-inducible direct repeat (DR)-4 elements, yet efficiently transactivate a DR-1 element derived from the endogenous PPAR-inducible acyl-CoA oxidase gene promoter. RXRalpha heterodimerization with CAR1, CAR76 and CAR80 isoforms is necessary for the DR-1 PPRE activation, a function that exhibits absolute dependence on both the respective RXRalpha DBD and CAR activation (AF)-2 domains, but not the AF-1 or AF-2 domain of RXRalpha, nor CAR's DBD. A new model of CAR DBD-independent transactivation is proposed, such that in the context of a DR-1 peroxisome proliferator-activated response element, only the RXRalpha portion of the CAR-RXRalpha heterodimer binds directly to DNA, with the AF-2 domain of tethered CAR mediating transcriptional activation of the receptor complex. PMID- 17355986 TI - ElrA binding to the 3'UTR of cyclin E1 mRNA requires polyadenylation elements. AB - The early cell divisions of Xenopus laevis and other metazoan embryos occur in the presence of constitutively high levels of the cell cycle regulator cyclin E1. Upon completion of the 12th cell division, a time at which many maternal proteins are downregulated by deadenylation and destabilization of their encoding mRNAs, maternal cyclin E1 protein is downregulated while its mRNA is polyadenylated and stable. We report here that stable polyadenylation of cyclin E1 mRNA requires three cis-acting elements in the 3' untranslated region; the nuclear polyadenylation sequence, a contiguous cytoplasmic polyadenylation element and an upstream AU-rich element. ElrA, the Xenopus homolog of HuR and a member of the ELAV gene family binds the cyclin E1 3'UTR with high affinity. Deletion of these elements dramatically reduces the affinity of ElrA for the cyclin E1 3'UTR, abolishes polyadenylation and destabilizes the mRNA. Together, these findings provide compelling evidence that ElrA functions in polyadenylation and stabilization of cyclin E1 mRNA via binding these elements. PMID- 17355987 TI - EST assembly supported by a draft genome sequence: an analysis of the Chlamydomonas reinhardtii transcriptome. AB - Clustering and assembly of expressed sequence tags (ESTs) constitute the basis for most genomewide descriptions of a transcriptome. This approach is limited by the decline in sequence quality toward the end of each EST, impacting both sequence clustering and assembly. Here, we exploit the available draft genome sequence of the unicellular green alga Chlamydomonas reinhardtii to guide clustering and to correct errors in the ESTs. We have grouped all available EST and cDNA sequences into 12,063 ACEGs (assembly of contiguous ESTs based on genome) and generated 15,857 contigs of average length 934 nt. We predict that roughly 3000 of our contigs represent full-length transcripts. Compared to previous assemblies, ACEGs show extended contig length, increased accuracy and a reduction in redundancy. Because our assembly protocol also uses ESTs with no corresponding genomic sequences, it provides sequence information for genes interrupted by sequence gaps. Detailed analysis of randomly sampled ACEGs reveals several hundred putative cases of alternative splicing, many overlapping transcription units and new genes not identified by gene prediction algorithms. Our protocol, although developed for and tailored to the C. reinhardtii dataset, can be exploited by any eukaryotic genome project for which both a draft genome sequence and ESTs are available. PMID- 17355988 TI - The unstructured C-terminus of the tau subunit of Escherichia coli DNA polymerase III holoenzyme is the site of interaction with the alpha subunit. AB - The tau subunit of Escherichia coli DNA polymerase III holoenzyme interacts with the alpha subunit through its C-terminal Domain V, tau(C)16. We show that the extreme C-terminal region of tau(C)16 constitutes the site of interaction with alpha. The tau(C)16 domain, but not a derivative of it with a C-terminal deletion of seven residues (tau(C)16Delta7), forms an isolable complex with alpha. Surface plasmon resonance measurements were used to determine the dissociation constant (K(D)) of the alpha-tau(C)16 complex to be approximately 260 pM. Competition with immobilized tau(C)16 by tau(C)16 derivatives for binding to alpha gave values of K(D) of 7 muM for the alpha-tau(C)16Delta7 complex. Low-level expression of the genes encoding tau(C)16 and tau(C)16triangle up7, but not tau(C)16Delta11, is lethal to E. coli. Suppression of this lethal phenotype enabled selection of mutations in the 3' end of the tau(C)16 gene, that led to defects in alpha binding. The data suggest that the unstructured C-terminus of tau becomes folded into a helix-loop-helix in its complex with alpha. An N-terminally extended construct, tau(C)24, was found to bind DNA in a salt-sensitive manner while no binding was observed for tau(C)16, suggesting that the processivity switch of the replisome functionally involves Domain IV of tau. PMID- 17355989 TI - Bioinformatic prediction and experimental verification of Fur-regulated genes in the extreme acidophile Acidithiobacillus ferrooxidans. AB - The gamma-proteobacterium Acidithiobacillus ferrooxidans lives in extremely acidic conditions (pH 2) and, unlike most organisms, is confronted with an abundant supply of soluble iron. It is also unusual in that it oxidizes iron as an energy source. Consequently, it faces the challenging dual problems of (i) maintaining intracellular iron homeostasis when confronted with extremely high environmental loads of iron and (ii) of regulating the use of iron both as an energy source and as a metabolic micronutrient. A combined bioinformatic and experimental approach was undertaken to identify Fur regulatory sites in the genome of A. ferrooxidans and to gain insight into the constitution of its Fur regulon. Fur regulatory targets associated with a variety of cellular functions including metal trafficking (e.g. feoPABC, tdr, tonBexbBD, copB, cdf), utilization (e.g. fdx, nif), transcriptional regulation (e.g. phoB, irr, iscR) and redox balance (grx, trx, gst) were identified. Selected predicted Fur regulatory sites were confirmed by FURTA, EMSA and in vitro transcription analyses. This study provides the first model for a Fur-binding site consensus sequence in an acidophilic iron-oxidizing microorganism and lays the foundation for future studies aimed at deepening our understanding of the regulatory networks that control iron uptake, homeostasis and oxidation in extreme acidophiles. PMID- 17355990 TI - Identification of putative transcriptional regulatory networks in Entamoeba histolytica using Bayesian inference. AB - Few transcriptional regulatory networks have been described in non-model organisms. In Entamoeba histolytica seminal aspects of pathogenesis are transcriptionally controlled, however, little is known about transcriptional regulatory networks that effect gene expression in this parasite. We used expression data from two microarray experiments, cis-regulatory motif elucidation, and a naive Bayesian classifier to identify genome-wide transcriptional regulatory patterns in E. histolytica. Our algorithm identified promoter motifs that accurately predicted the gene expression level of 68% of genes under trophozoite conditions. We identified a promoter motif ((A)/(T)AAACCCT) associated with high gene expression, which is highly enriched in promoters of ribosomal protein genes and tRNA synthetases. Additionally, we identified three promoter motifs (GAATGATG, AACTATTTAAACAT(C)/(T)C and TGAACTTATAAACATC) associated with low gene expression. The promoters of a large gene family were highly enriched for these motifs, and in these genes the presence of >/=2 motifs predicted low baseline gene expression and transcriptional activation by heat shock. We demonstrate that amebic nuclear protein(s) bind specifically to four of the motifs identified herein. Our analysis suggests that transcriptional regulatory networks can be identified using limited expression data. Thus, this approach is applicable to the multitude of systems for which microarray and genome sequence data are emerging. PMID- 17355991 TI - In vivo and in vitro investigation of bacterial type B RNase P interaction with tRNA 3'-CCA. AB - For catalysis by bacterial type B RNase P, the importance of a specific interaction with p(recursor)tRNA 3'-CCA termini is yet unclear. We show that mutation of one of the two G residues assumed to interact with 3'-CCA in type B RNase P RNAs inhibits cell growth, but cell viability is at least partially restored at increased RNase P levels due to RNase P protein overexpression. The in vivo defects of the mutant enzymes correlated with an enzyme defect at low Mg(2+) in vitro. For Bacillus subtilis RNase P, an isosteric C259-G(74) bp fully and a C258-G(75) bp slightly rescued catalytic proficiency, demonstrating Watson Crick base pairing to tRNA 3'-CCA but also emphasizing the importance of the base identity of the 5'-proximal G residue (G258). We infer the defect of the mutant enzymes to primarily lie in the recruitment of catalytically relevant Mg(2+), with a possible contribution from altered RNA folding. Although with reduced efficiency, B. subtilis RNase P is able to cleave CCA-less ptRNAs in vitro and in vivo. We conclude that the observed in vivo defects upon disruption of the CCA interaction are either due to a global deceleration in ptRNA maturation or severe inhibition of 5'-maturation for a ptRNA subset. PMID- 17355992 TI - A novel microarray approach reveals new tissue-specific signatures of known and predicted mammalian microRNAs. AB - Microarrays to examine the global expression levels of microRNAs (miRNAs) in a systematic in-parallel manner have become important tools to help unravel the functions of miRNAs and to understand their roles in RNA-based regulation and their implications in human diseases. We have established a novel miRNA-specific microarray platform that enables the simultaneous expression analysis of both known and predicted miRNAs obtained from human or mouse origin. Chemically modified 2'-O-(2-methoxyethyl)-(MOE) oligoribonucleotide probes were arrayed onto Evanescent Resonance (ER) microchips by robotic spotting. Supplementing the complementary probes against miRNAs with carefully designed mismatch controls allowed for accurate sequence-specific determination of miRNA expression profiles obtained from a panel of mouse tissues. This revealed new expression signatures of known miRNAs as well as of novel miRNAs previously predicted using bioinformatic methods. Systematic confirmation of the array data with northern blotting and, in particular, real-time PCR suggests that the described microarray platform is a powerful tool to analyze miRNA expression patterns with rapid throughput and high fidelity. PMID- 17355993 TI - Fetal growth in early pregnancy and risk of delivering low birth weight infant: prospective cohort study. AB - OBJECTIVE: To determine if first trimester fetal growth is associated with birth weight, duration of pregnancy, and the risk of delivering a small for gestational age infant. DESIGN: Prospective cohort study of 38 033 pregnancies between 1999 and 2003. SETTING: 15 centres representing major regions of the United States. PARTICIPANTS: 976 women from the original cohort who conceived as the result of assisted reproductive technology, had a first trimester ultrasound measurement of fetal crown-rump length, and delivered live singleton infants without evidence of chromosomal or congenital abnormalities. First trimester growth was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. MAIN OUTCOME MEASURES: Birth weight, duration of pregnancy, and risk of delivering a small for gestational age infant. RESULTS: For each one day increase in the observed size of the fetus, birth weight increased by 28.2 (95% confidence interval 14.6 to 41.2) g. The association was substantially attenuated by adjustment for duration of pregnancy (adjusted coefficient 17.1 (6.6 to 27.5) g). Further adjustments for maternal characteristics and complications of pregnancy did not have a significant effect. The risk of delivering a small for gestational age infant decreased with increasing size in the first trimester (odds ratio for a one day increase 0.87, 0.81 to 0.94). The association was not materially affected by adjustment for maternal characteristics or complications of pregnancy. CONCLUSION: Variation in birth weight may be determined, at least in part, by fetal growth in the first 12 weeks after conception through effects on timing of delivery and fetal growth velocity. PMID- 17355994 TI - Internet provision of tailored advice on falls prevention activities for older people: a randomized controlled evaluation. AB - Falls are very common in older persons and can result in substantial disability and distress. By undertaking strength and balance training (SBT) exercises, older people can reduce their risk of falling. The Internet offers a potentially cost effective means of disseminating information about SBT to older people and their carers. A particular advantage of using the Internet for this purpose is that the advice given can be 'tailored' to the needs of the individual. This study used a randomized controlled design to evaluate an interactive web-based program that tailored advice about undertaking SBT activities. The participants were 280 people with an age range of 65-97 years recruited by advertising the website by email and the Internet. Those randomized to the tailored advice were presented with advice tailored to their personal self-rated balance capabilities, health problems and activity preferences. Those in the control group were presented with all the advice from which the tailored advice was selected. After reading the advice, those in the tailored advice group (n = 144) had more positive attitudes (p < 0.01) than those in the control group (n = 136), reporting greater perceived relevance of the SBT activities, greater confidence in the ability to carry them out, and hence stronger intentions to undertake the activities. This study provides an initial indication that an interactive website might offer a cost effective way to provide personalized advice to some older people. Further research is required to determine whether website-based advice on falls prevention changes behavior as well as intentions and whether the advice needs to be supplemented by other forms of support. PMID- 17355995 TI - Healthy public policy in poor countries: tackling macro-economic policies. AB - Large segments of the population in poor countries continue to suffer from a high level of unmet health needs, requiring macro-level, broad-based interventions. Healthy public policy, a key health promotion strategy, aims to put health on the agenda of policy makers across sectors and levels of government. Macro-economic policy in developing countries has thus far not adequately captured the attention of health promotion researchers. This paper argues that healthy public policy should not only be an objective in rich countries, but also in poor countries. This paper takes up this issue by reviewing the main macro-economic aid programs offered by international financial institutions as a response to economic crises and unmanageable debt burdens. Although health promotion researchers were largely absent during a key debate on structural adjustment programs and health during the 1980s and 1990s, the international macro-economic policy tool currently in play offers a new opportunity to participate in assessing these policies, ensuring new forms of macro-economic policy interventions do not simply reproduce patterns of (neoliberal) economics-dominated development policy. PMID- 17355996 TI - Determination of flower structure in Elaeis guineensis: do palms use the same homeotic genes as other species? AB - AIMS: In this article a review is made of data recently obtained on the structural diversity and possible functions of MADS box genes in the determination of flower structure in the African oil palm (Elaeis guineensis). MADS box genes play a dominant role in the ABC model established to explain how floral organ identity is determined in model dicotyledon species such as Arabidopsis thaliana and Antirrhinum majus. In the monocotyledons, although there appears to be a broad general conservation of ABC gene functions, the model itself needs to be adapted in some cases, notably for certain species which produce flowers with sepals and petals of similar appearance. For the moment, ABC genes remain unstudied in a number of key monocot clades, so only a partial picture is available for the Liliopsida as a whole. The aim of this article is to summarize data recently obtained for the African oil palm Elaeis guineensis, a member of the family Arecaceae (Arecales), and to discuss their significance with respect to knowledge gained from other Angiosperm groups, particularly within the monocotyledons. SCOPE: The essential details of reproductive development in oil palm are discussed and an overview is provided of the structural and functional characterization of MADS box genes likely to play a homeotic role in flower development in this species. CONCLUSIONS: The structural and functional data provide evidence for a general conservation of the generic 'ABC' model in oil palm, rather than the 'modified ABC model' proposed for some other monocot species which produce homochlamydeous flowers (i.e. with morphologically similar organs in both perianth whorls), such as members of the Liliales. Our oil palm data therefore follow a similar pattern to those obtained for other Commelinid species in the orders Commelinales and Poales. The significance of these findings is discussed. PMID- 17355997 TI - Panitumumab: a fully human monoclonal antibody with activity in metastatic colorectal cancer. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trials, adverse effects, and drug interactions of panitumumab. DATA SOURCES: A MEDLINE search was conducted (1966-February 2007) using the search terms panitumumab, ABX-EGF, E7.6.3, monoclonal antibody, colorectal neoplasm, epidermal growth factor receptor, EGFr, and epidermal growth factor receptor signal transduction. Articles and abstracts were further identified from the American Society of Clinical Oncology and the National Comprehensive Cancer Network. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating panitumumab for solid tumors were selected from the data sources. All published relevant abstracts were included. DATA SYNTHESIS: The most recent developments in the treatment of metastatic colorectal cancer include the monoclonal antibodies targeted against vascular endothelial growth factor and the epidermal growth factor receptor (EGFr). Panitumumab is the first fully human monoclonal antibody that binds to EGFr. Clinical activity has been demonstrated, most notably in patients with EGFr positive metastatic colorectal cancer who have failed prior therapy. Phase III study results indicate a 46% reduction in the rate of tumor progression in treated patients compared with those who received best supportive care alone. Panitumumab is well tolerated, with acneiform rash the most common dose-dependent adverse effect. Studies thus far indicate a low rate of infusion-related reactions (1%, grade 3-4). CONCLUSIONS: Panitumumab is a fully human monoclonal antibody with promising activity in treatment of patients with metastatic colorectal cancer who have failed previous therapy, offering a favorable safety profile. PMID- 17355998 TI - Bevacizumab for neovascular ocular diseases. AB - OBJECTIVE: To review the efficacy and safety of off-label use of bevacizumab for neovascular ocular diseases. DATA SOURCES: A PubMed (1966-January 2007) search was conducted using the terms human, intravitreal, bevacizumab, macular, and retinopathy. Meeting abstracts from the American Academy of Ophthalmology, Retina Society, Macula Society, and Association for Research in Vision and Ophthalmology were reviewed. STUDY SELECTION AND DATA EXTRACTION: Controlled studies, unpublished reports involving 100 or more subjects, and published reports describing 5 or more subjects were reviewed. Only English-language articles were considered. DATA SYNTHESIS: Intravitreal bevacizumab has been evaluated in 133 patients in unpublished controlled studies. Over 3500 patients have been evaluated in open-label studies with duration of follow-up ranging from 3 months to 1 year. The most common use was neovascular age-related macular degeneration (AMD). Other conditions studied included diabetic retinopathy, pathological myopia, neovascular glaucoma, and macular edema due to diabetes, retinal vein occlusion, or uveitis. Statistically significant improvements in visual acuity, as well as decreases in retinal thickness and the extent of choroidal neovascularization, were noted. Intravitreal bevacizumab was well tolerated over the short term. In a registry compiling adverse experiences of 7113 intravitreal injections, rates of adverse events were less than or equal to 0.21%. CONCLUSIONS: Uncontrolled studies support a benefit of intravitreal bevacizumab in neovascular AMD for 3 months to 1 year. Low cost is a significant advantage of bevacizumab. Patients should discuss the potential risks and benefits of intravitreal bevacizumab and other available therapies with their physicians before receiving treatment. Controlled trials are needed to characterize the safety and efficacy of intravitreal bevacizumab and determine the optimal treatment regimen. PMID- 17355999 TI - Systemic anticoagulant prophylaxis for central catheter-associated venous thrombosis in cancer patients. AB - OBJECTIVE: To review the literature regarding the incidence of thrombosis in cancer patients with central venous catheters (CVCs) and weigh the evidence supporting thromboprophylaxis in this patient population. DATA SOURCES: Clinical literature was identified by searching MEDLINE (1966-February 2007) using the key search terms malignancy, cancer, catheters, prophylaxis, thrombosis, and central venous catheters. STUDY SELECTION AND DATA EXTRACTION: An evaluation of retrospective and prospective clinical trials that studied the use of systemic anticoagulants (eg, warfarin, heparin, and low-molecular-weight heparin [LMWH]) to prevent thrombosis with CVCs was performed. Different patient populations, including those manifesting with solid tumor or hematologic malignancy and those undergoing hematopoietic stem cell transplant, were evaluated for this review. DATA SYNTHESIS: Thrombosis associated with CVCs is a common complication in cancer patients. Most CVC thrombosis will occur within 30 days after placement, with a majority within 8 days. The incidence may depend on the type of CVC and location of the catheter tip. Despite recommendations against the use of systemic anticoagulation for prophylaxis against CVC thrombosis, a potential role continues to be explored in selected settings. Several variables are noted between published clinical trials, making any comparisons difficult to determine whether any benefit exists. Generally, the use of mini-dose warfarin, LMWH, or low-dose unfractionated heparin did not consistently reach significance in reporting a reduction in CVC thrombosis. CONCLUSIONS: Available data do not support the routine use of anticoagulants for thromboprophylaxis to prevent CVC related thrombosis. However, several inconsistencies can be found in the studies done to date. More studies are needed to identify subsets of cancer patients who are at higher risk of developing CVC thrombosis and may benefit from prophylactic systemic anticoagulation. PMID- 17356002 TI - National audit of continence care for older people: management of faecal incontinence. AB - INTRODUCTION: Faecal incontinence in older people is associated with considerable morbidity but is amenable to successful management. Quality standards in this area were previously subject to a pilot audit in primary, secondary care and care homes to allow providers to compare the care delivered by their service to others and to monitor the development of integrated continence services as set out in the National Service Framework for Older People. This study reports the results of the national audit. RESULTS: Data were returned by 141 primary care sites, 159 secondary care trusts (involving 198 hospitals) and 29 care homes. Data on the care of 3,059 patients/residents with bowel problems were analysed. Fifty-eight per cent of Primary Care Trusts (PCTs), 48% of hospitals and 74% of care homes reported that integrated continence services existed in their areas. Whilst basic provision of care appeared to be in place, the audit identified deficiencies in the organisation of services and in the assessment and management of faecal incontinence. CONCLUSION: The results of this audit indicate that the requirement for integrated continence services contained within the National Service Framework for Older People has not yet been met. Basic assessment and care by the professionals directly looking after older persons is often lacking. There is an urgent need to re-establish the fundamentals of continence care into the daily practice of medical and nursing staff, and undoubtedly, action needs to be taken with regard to the establishment of truly integrated, quality services in this neglected area of practice. PMID- 17356003 TI - A randomised controlled trial of Tai Chi and resistance exercise on bone health, muscle strength and balance in community-living elderly people. AB - BACKGROUND: The beneficial role of exercise in improving bone mineral density, muscle strength and balance, has been documented predominantly in younger populations. These findings may not apply to elderly populations with limited ability to perform exercises of high intensity. OBJECTIVE: To examine the effects of Tai Chi (TC) and resistance exercise (RTE) on bone mineral density (BMD), muscle strength, balance and flexibility in community living elderly people. DESIGN: Randomised controlled trial, using blocked randomization with stratification by sex. SETTING: A community in the New Territories Region of Hong Kong, China. SUBJECTS: One hundred eighty subjects (90 men, 90 women) aged 65-74, were recruited through advertisements in community centres. METHODS: Subjects were assigned to participate in TC, RTE three times a week, or no intervention (C) for 12 months. Measurements were carried out at baseline, 6 and 12 months. Analyses of covariance (ANCOVA) adjusted for age, and baseline values of variables that were significantly different between groups: i.e. smoking and flexibility for men; quadriceps strength for women. RESULTS: Compliance was high (TC 81%, RTE 76%). In women, both TC and RTE groups had less BMD loss at total hip compared with controls. No effect was observed in men. No difference in either balance, flexibility or the number of falls was observed between either intervention or controls after 12 months. CONCLUSION: The beneficial effects of TC or RTE on musculoskeletal health are modest and may not translate into better clinical outcomes. PMID- 17356004 TI - LIF-mediated control of embryonic stem cell self-renewal emerges due to an autoregulatory loop. AB - Stem cells convert graded stimuli into all-or-nothing cell-fate responses. We investigated how embryonic stem cells (ESCs) convert leukemia inhibitory factor (LIF) concentration into an all-or-nothing cell-fate decision (self-renewal). Using a combined experimental/computational approach we demonstrate unexpected switch-like (on/off) signaling in response to LIF. This behavior emerges over time due to a positive feedback loop controlling transcriptional expression of LIF signaling pathway components. The autoregulatory loop maintains robust pathway responsiveness ("on") at sufficient concentrations of exogenous LIF, while autocrine signaling and low concentrations of exogenous LIF cause ESCs to adopt the weakly responsive ("off") state of differentiated cells. We demonstrate that loss of ligand responsiveness is reversible and precedes loss of the ESC transcription factors Oct4 and Nanog, suggesting an early step in the hierarchical control of differentiation. While endogenously produced ligands were insufficient to sustain the "on" state, they buffer it, influencing the timing of differentiation. These results demonstrate a novel switch-like behavior, which establishes the LIF threshold for ESC self-renewal. PMID- 17356005 TI - Enduring vulnerability to reinstatement of methamphetamine-seeking behavior in glial-cell-line-derived neurotrophic factor mutant mice. AB - Genetic factors are considered to play an important role in drug dependence/addiction including the development of drug dependence and relapse. With the use of a model of drug self-administration in mutant mice, several specific genes and proteins have been identified as potentially important in the development of drug dependence. In contrast, little is known about the role of specific genes in enduring vulnerability to relapse, a clinical hallmark of drug addiction. Using a mouse model of reinstatement, which models relapse of drug seeking behavior in addicts, we provide evidence that a partial reduction in the expression of the glial cell line-derived neurotrophic factor (GDNF) potentiates methamphetamine (METH) self-administration, enhances motivation to take METH, increases vulnerability to drug-primed reinstatement, and prolongs cue-induced reinstatement of extinguished METH-seeking behavior. In contrast, there was no significant difference in novelty responses, METH-stimulated hyperlocomotion and locomotor sensitization, food-reinforced operant behavior and motivation, or reinstatement of food-seeking behavior between GDNF heterozygous knockout mice and wild-type littermates. These findings suggest that GDNF may be associated with enduring vulnerability to reinstatement of METH-seeking behavior and a potential target in the development of therapies to control relapse. PMID- 17356006 TI - EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer's disease. AB - Standardized Ginkgo biloba extract EGb 761 exhibits beneficial effects to patients with Alzheimer's disease (AD). It was previously demonstrated that EGb 761 inhibits amyloid beta (Abeta) oligomerization in vitro, protects neuronal cells against Abeta toxicity, and improves cognitive defects in a mouse model of AD (Tg 2576). In this study, the neurogenic potential of EGb 761 and its effect on cAMP response element binding protein (CREB) were examined in a double transgenic mouse model (TgAPP/PS1). EGb 761 significantly increases cell proliferation in the hippocampus of both young (6 months) and old (22 months) TgAPP/PS1 mice, and the total number of neuronal precursor cells in vitro in a dose-dependent manner. Furthermore, Abeta oligomers inhibit phosphorylation of CREB and cell proliferation in the hippocampus of TgAPP/PS1 mice. Administration of EGb 761 reduces Abeta oligomers and restores CREB phosphorylation in the hippocampus of these mice. The present findings suggest that 1) enhanced neurogenesis by EGb 761 may be mediated by activation of CREB, 2) stimulation of neurogenesis by EGb 761 may contribute to its beneficial effects in AD patients and improved cognitive functions in the mouse model of AD, and 3) EGb 761 has therapeutic potential for the prevention and improved treatment of AD. PMID- 17356007 TI - Fast skeletal muscle regulatory light chain is required for fast and slow skeletal muscle development. AB - In skeletal muscle, the myosin molecule contains two sets of noncovalently attached low molecular weight proteins, the regulatory (RLC) and essential (ELC) light chains. To assess the functional and developmental significance of the fast skeletal isoform of the RLC (RLC-f), the murine fast skeletal RLC gene (Mylpf) was disrupted by homologous recombination. Heterozygotes containing an intronic neo cassette (RLC-/+) had approximately one-half of the amount of the RLC-f mRNA compared to wild-type (WT) mice but their muscles were histologically normal in both adults and neonates. In contrast, homozygous mice (RLC-/-) had no RLC-f mRNA or protein and completely lacked both fast and slow skeletal muscle. This was likely due to interference with mRNA processing in the presence of the neo cassette. These RLC-f null mice died immediately after birth, presumably due to respiratory failure since their diaphragms lacked skeletal muscle. The body weight of newborn RLC-f null mice was decreased 30% compared to heterozygous or WT newborn mice. The lack of skeletal muscle formation in the null mice did not affect the development of other organs including the heart. In addition, we found that WT mice did not express the ventricular/slow skeletal RLC isoform (RLC-v/s) until after birth, while it was expressed normally in the embryonic heart. The lack of skeletal muscle formation observed in RLC-f null mice indicates the total dependence of skeletal muscle development on the presence of RLC-f during embryogenesis. This observation, along with the normal function of the RLC-v/s in the heart, implicates a coupled, diverse pathway for RLC-v/s and RLC-f during embryogenesis, where RLC-v/s is responsible for heart development and RLC-f is necessary for skeletal muscle formation. In conclusion, in this study we demonstrate that the Mylpf gene is critically important for fast and slow skeletal muscle development. PMID- 17356008 TI - Globular adiponectin resistance develops independently of impaired insulin stimulated glucose transport in soleus muscle from high-fat-fed rats. AB - High-fat (HF) diets induce insulin resistance and alter lipid metabolism, although controversy exists regarding the impact of saturated vs. polyunsaturated fats. Adiponectin (Ad) stimulates fatty acid (FA) oxidation and improves insulin sensitivity in humans and rodents, due in part to the activation of AMP-activated protein kinase (AMPK) and subsequent deactivation of acetyl coenzyme A carboxylase (ACC). In genetically obese, diabetic mice, this acute stimulatory effect on AMPK in muscle is lost. The ability of a HF diet to induce skeletal muscle Ad resistance has not been examined. The purpose of this study was to determine whether Ad's effects on FA oxidation and AMPK/ACC would be reduced following different HF diets, and if this coincided with the development of impaired maximal insulin-stimulated glucose transport. Rats were fed a control (10% kcal fat, CON), high unsaturated fat (60% kcal safflower oil, SAFF), or high saturated fat diet (60% kcal lard, LARD) for 4 wk. Following the dietary intervention, glucose transport, lipid metabolism, and AMPK/ACC phosphorylation were measured in the presence and absence of globular Ad (gAd, 2.5 microg/ml) in isolated soleus muscle. LARD rats showed reduced rates of maximal insulin stimulated glucose transport compared with CON and SAFF (+68 vs. +172 and +184%, P < or = 0.001). gAd increased pACC (+25%, P < or = 0.01) and FA oxidation (+28%, P < or = 0.05) in CON rats, but not in either HF group. Thus 4 wk of HF feeding results in the loss of gAd stimulatory effect on ACC phosphorylation and muscle FA oxidation, and this can occur independently of impaired maximal insulin stimulated glucose transport. PMID- 17356009 TI - Maternal exposure to dexamethasone or cortisol in early pregnancy differentially alters insulin secretion and glucose homeostasis in adult male sheep offspring. AB - An adverse intrauterine environment increases the risk of developing various adult-onset diseases, whose nature varies with the timing of exposure. Maternal undernutrition in humans can increase adiposity, and the risk of coronary heart disease and impaired glucose tolerance in adult life, which may be partly mediated by maternal or fetal endocrine stress responses. In sheep, dexamethasone in early pregnancy impairs cardiovascular function, but not glucose homeostasis in adult female offspring. However, male offspring are often more susceptible to early life "programming". Pregnant sheep were infused intravenously with saline (0.19 ml/h), dexamethasone (0.48 mg/h), or cortisol (5 mg/h), for 2 days from 26 to 28 days of gestation. In male offspring, size at birth and postnatal growth were measured, and glucose tolerance [intravenous glucose tolerance test (IVGTT)], insulin secretion, and insulin sensitivity of glucose, alpha-amino nitrogen, and free fatty acid metabolism were assessed at 4 yr of age. We show that cortisol, but not dexamethasone, treatment of mothers causes fasting hyperglycemia in adult male offspring. Maternal cortisol induced a second-phase hyperinsulinemia during IVGTT, whereas maternal dexamethasone induced a first phase hyperinsulinemia. Dexamethasone improved glucose tolerance, while cortisol had no impact, and neither affected insulin sensitivity. This suggests that maternal glucocorticoid exposure in early pregnancy alters glucose homeostasis and induces hyperinsulinemia in adult male offspring, but in a glucocorticoid specific manner. These consequences of glucocorticoid exposure in early pregnancy may lead to pancreatic exhaustion and diabetes longer term and are consistent with stress during early pregnancy contributing to such outcomes in humans. PMID- 17356010 TI - Impaired insulin secretion in a mouse model of ataxia telangiectasia. AB - Ataxia telangiectasia (A-T) is an autosomal recessive disease caused by mutations in the A-T mutated (ATM) gene. The gene encodes a serine/threonine kinase with important roles in the cellular response to DNA damage, including the activation of cell cycle checkpoints and induction of apoptosis. Although these functions might explain the cancer predisposition of A-T patients, the molecular mechanisms leading to glucose intolerance and diabetes mellitus (DM) are unknown. We have investigated the pathogenesis of DM in a mouse model of A-T. Here we show that young Atm-deficient mice show normal fasting glucose levels and normal insulin sensitivity. However, oral glucose tolerance testing revealed delayed insulin secretion and resulting transient hyperglycemia. Aged Atm-/- mice show a pronounced increase in blood glucose levels and a decrease in insulin and C peptide levels. Our findings support a role for ATM in metabolic function and point toward impaired insulin secretion as the primary cause of DM in A-T. PMID- 17356011 TI - The major facilitator superfamily member Slc37a2 is a novel macrophage- specific gene selectively expressed in obese white adipose tissue. AB - A marked degree of macrophage infiltration of white adipose tissue (WAT) occurs in obesity and may link excess adiposity with the chronic inflammatory state underlying metabolic syndrome and other comorbidities of obesity. Excess deposition of fat in the intra-abdominal vs. subcutaneous WAT depots is a key component of metabolic syndrome. Through construction and differential screening of a murine ob/ob WAT cDNA library, we identified Slc37a2, a novel sugar transporter of the major facilitator superfamily, to be twofold enriched in intra abdominal vs. subcutaneous fat. We find Slc37a2 is a macrophage-enriched transcript. In murine tissues, Slc37a2 transcript is restricted to spleen, thymus, and obese WAT. It is also readily detected in the RAW264.7 macrophage cell line and increases 46-fold during macrophage differentiation of THP-1 human monocytes. Compared with wild-type mice, Slc37a2 transcript is increased epididymal ninefold in ob/ob WAT and assessment of expression of the macrophage marker emr1 indicated upregulation of Slc37a2 transcript in macrophages populating ob/ob WAT. Studies with PNGase F and tunicamycin reveal the Slc37a2 protein is posttranslationally modified by addition of N-linked glycans. Slc37a2 protein migrates as heterogeneous species of approximately 50-75 kDa and its ectopic expression in mammalian cells results in the appearance of large intracellular vacuoles. We postulate that the function of this macrophage specific putative sugar transporter is central to the metabolism of the macrophage population specifically present in obese WAT. PMID- 17356012 TI - The pattern of activation of the sympathetic nervous system during tilt-induced syncope. AB - A 49-year-old patient with a history of situational syncope and minimal electrocardiographic signs of accessory pathway is described. The evidence for pre-excitation was present only during the sympathetic activation caused by exercise testing and isoprenaline infusion. This phenomenon served as an indicator of significant adrenergic drive to the heart after the tilt-induced syncope. The meaning of the observed electrocardiographic changes in the course of neurocardiogenic reaction and its contribution to the understanding of the sympatho-vagal balance during vasovagal syncope is discussed. The lack of preexcitation signs during syncope and its appearance several seconds after the syncope-related sinus pause indicates sympathetic withdrawal before and shortly after the asystole. The possible pathophysiological mechanisms are discussed. PMID- 17356013 TI - Prevalence of Brugada sign in patients presenting with palpitation in southern Iran. AB - AIMS: Brugada syndrome is a cardiac channel abnormality that is associated with a high risk of ventricular fibrillation and sudden cardiac death and characterized by an electrocardiographic pattern of right bundle branch block and transient or persistent ST-segment elevation in leads V1-V3. No data regarding the frequency of Brugada syndrome exist in an Iranian population. The aim of this study was to determine the frequency of Brugada-type ECG pattern in southern Iran. METHODS AND RESULTS: All patients presenting with palpitation were enrolled in the study. A Brugada-type ECG pattern was determined according to the criteria recommended by European Heart Association Molecular Basis of Arrhythmias Study Group. A total of 3895 patients (mean age 38.2 +/- 11.9 years, 54% women) met all study criteria. One hundred patients (2.56%) had Brugada-type ECG pattern. Of these, 21 patients (0.54%) had definite Brugada sign (Type 1 or Types 2 and 3 with conversion to Type 1 following procainamide test). Of 21 patients with definite Brugada sign, eight had Brugada syndrome, four had history of syncope, two had coved-type ECG in the family, one had polymorphic ventricular tachycardia, and one had history of sudden cardiac death in the family. Five patients underwent ICD implantation. The incidence of a Brugada-type ECG pattern was 2.43% in subjects between 17 and 30 years and 0.13% in subjects >30 years (P = 0.01). CONCLUSION: Frequency of Brugada sign in an Iranian population presenting with palpitation is greater than some European countries and lower than a Japanese urban population. PMID- 17356014 TI - Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates. AB - Mitochondrial abnormalities represent a major cytopathology in Huntington's disease (HD), a fatal neurodegenerative disease caused by CAG repeat expansions in the gene encoding huntingtin (Htt). In the present study, we investigated whether defects in the mitochondrial respiratory function are consequences of the expression of mutant Htt or they promote the formation of Htt aggregates. To take advantage of existing mitochondrial DNA mutants, we developed human osteosarcoma 143B cells expressing mutant Htt in an inducible manner and found that cells expressing mutant Htt but not wild-type Htt exhibited a reduced activity of complex III and an increased activity of complex IV. Conversely, pharmacological treatments that inhibited complex III activity significantly promoted the formation of Htt aggregates. This complex III-mediated modulation of Htt aggregates was also observed in a neuronal progenitor RN33B cell line transduced by lentivirus carrying mutant Htt. This effect of complex III inhibition on the Htt aggregates appeared to be mediated by the inhibition of proteasome activity, but not by ATP depletion or production of reactive oxygen species. Accordingly, complex III mutant cells also showed decreased proteasome activity. These results suggest the presence of a feedback system connecting the mitochondrial respiratory complex III and the production of Htt aggregates. Our results suggest that therapeutic interventions targeting complex III and/or proteasome could ameliorate the progress of HD. PMID- 17356015 TI - Comprehensive QTL analysis of serum cholesterol levels before and after a high cholesterol diet in SHRSP. AB - The stroke-prone spontaneously hypertensive rat (SHRSP) showed an exaggerated response to a high-fat, high-cholesterol (HFC) diet, and the resulting reactive hypercholesterolemia was suggested to exacerbate the atherogenic process in this rat. We thus performed a quantitative trait locus (QTL) analysis on the serum cholesterol level of SHRSP before and after the HFC diet, with the final goal being the identification of the genetic mechanisms of its reactive hypercholesterolemia. Three hundred fifty-eight F2 rats between SHRSP and Wistar Kyoto rat were employed in the study. The serum cholesterol and apoprotein E were measured before and after 2 wk of feeding with the HFC diet. Multiple QTLs for the basal cholesterol level were identified on chromosomes 1 and 5, whereas those for the postdietary cholesterol level were on chromosomes 7, 15, and 16. The cholesterol QTLs before and after HFC diet did not overlap with one another, implying that the involved metabolic processes were considerably different between the two conditions. Supporting this, VLDL and LDL cholesterol were the major components of the postdietary serum cholesterol, whereas the basal cholesterol level consisted mainly of HDL cholesterol. A substantial difference of the QTLs between males and females was observed, especially after the HFC diet. The QTL on chromosome 15 had an inverse effect on the cholesterol level, suggesting that the congenic substitution of the SHRSP fragment with that of Wistar-Kyoto rats could induce a greater cholesterol level in SHRSP. This observation is significant in establishing a new model for atherosclerosis with hypertension in rats. PMID- 17356016 TI - Quantitative genetic basis of arterial phenotypes in the Brown Norway rat. AB - The Brown Norway (BN) rat presents several genetically determined arterial phenotypes of interest, i.e., ruptures of the internal elastic lamina (RIEL) in the abdominal aorta (AA), iliac (IAs), and renal arteries, aortic elastin deficit and higher frequency of persistent ductus arteriosus (PDA) than other strains. We investigated the genetic basis of these phenotypes. We established a backcross between BN and the LOU reference strain and performed a genome-wide scan on 104 males and 105 females with 193 microsatellite markers followed by linkage analysis. RIEL in AA and IAs showed highly significant linkage to a locus on chromosome 5 and suggestive linkage to a locus on chromosome 10, which is syntenic to one linked to a syndrome of thoracic aortic aneurysms with PDA in humans. In contrast, renal artery RIEL mapped to a chromosome 3 locus and thoracic aortic elastic content to two loci on chromosome 2. PDA was significantly linked to two different quantitative trait loci (QTL) on chromosomes 8 and 9. This is the first study in rats to identify genetic loci for PDA. We identified 21 candidate genes by functional relevance or integration of our mapping data with global expression analysis. Sequencing these genes identified 47 single nucleotide polymorphisms, but no functionally relevant amino acid changes. By expression analysis, myosin heavy chain 10, nonmuscle, in the chromosome 10 QTL, emerged as a candidate for RIEL in AA and IAs. Furthermore, production of a congenic line for the chromosome 5 QTL proved implication of this locus in RIEL formation. PMID- 17356017 TI - The cover. Mother Protecting Her Child. PMID- 17356018 TI - A piece of my mind. What makes a difference. PMID- 17356019 TI - Looming shortage of physicians raises concerns about access to care. PMID- 17356020 TI - Poverty shift may burden health system. PMID- 17356021 TI - Uwe Reinhardt, PhD: assessing US health insurance coverage. PMID- 17356022 TI - Statin use and risks for death and hospitalization in chronic heart failure. PMID- 17356023 TI - Statin use and risks for death and hospitalization in chronic heart failure. PMID- 17356024 TI - Classifying systolic and diastolic heart failure. PMID- 17356025 TI - Chlorhexidine gluconate for prevention of nosocomial infection in cardiac surgery. PMID- 17356026 TI - Association between rates of HIV testing and elimination of written consents in San Francisco. PMID- 17356027 TI - Financial barriers to health care and outcomes after acute myocardial infarction. AB - CONTEXT: The prevalence and consequences of financial barriers to health care services and medications are not well documented for patients with an acute myocardial infarction (AMI). OBJECTIVE: To measure the baseline prevalence of self-reported financial barriers to health care services or medication (as defined by avoidance due to cost) among individuals following AMI and their association with subsequent health care outcomes. DESIGN, SETTING, AND PARTICIPANTS: The Prospective Registry Evaluating Myocardial Infarction: Event and Recovery (PREMIER), an observational, multicenter US study of patients with AMI over 12 months in 2498 individuals enrolled from January 2003 through June 2004. MAIN OUTCOME MEASURES: Health status symptoms (Seattle Angina Questionnaire [SAQ]), overall health status function (Short Form-12), and rehospitalization. RESULTS: The prevalence of self-reported financial barriers to health care services or medication was 18.1% and 12.9%, respectively. Among individuals who reported financial barriers to health care services or medication, 68.9% and 68.5%, respectively, were insured. At 1-year follow-up, individuals with financial barriers to health care services were more likely to have lower SAQ quality-of-life score (77.9 vs 86.2; adjusted mean difference= -4.0; 95% confidence interval [CI], -6.3 to -1.8), and increased rates of all-cause rehospitalization (49.3% vs 38.1%; adjusted hazard ratio [HR], 1.3; 95% CI, 1.1 1.5) and cardiac rehospitalization (25.7% vs 17.7%; adjusted HR, 1.3; 95% CI, 1.0 1.6). At 1-year follow-up, individuals with financial barriers to medication were more likely to have angina (34.9% vs 17.9%; adjusted odds ratio, 1.55; 95% CI, 1.1-2.2), lower SAQ quality-of-life score (74.0 vs 86.1; adjusted mean difference = -7.6; 95% CI, -10.2 to -4.9), and increased rates of all-cause rehospitalization (57.0% vs 37.8%; risk-adjusted HR, 1.5; 95% CI, 1.2-1.8) and cardiac rehospitalization (33.7% vs 17.3%; adjusted HR, 1.7; 95% CI, 1.3-2.2). CONCLUSION: Financial barriers to health care services and medications are associated with worse recovery after AMI, manifested as more angina, poorer quality of life, and higher risk of rehospitalization. PMID- 17356028 TI - Insurance coverage, medical care use, and short-term health changes following an unintentional injury or the onset of a chronic condition. AB - CONTEXT: Given the large and increasing number of uninsured US individuals, identifying the health consequences of being uninsured has assumed increased importance. OBJECTIVE: To compare medical care use and short-term health changes among US uninsured individuals and insured nonelderly individuals following a health shock caused by either an unintentional injury or the onset of a chronic condition. DESIGN, SETTING, AND PARTICIPANTS: Multivariate logistic regression analysis of longitudinal data from Medical Expenditure Panel Surveys (1997-2004) limited to nonelderly individuals whose insurance status was established for 2 months prior to 1 or more unintentional injuries (20 783 cases among 15 866 individuals) and onset of 1 or more chronic conditions (10 485 cases among 7954 individuals). MAIN OUTCOME MEASURES: Self-reported medical care use and change in short-term general health status following the health shock. RESULTS: After experiencing a health shock, uninsured individuals were less likely to obtain any medical care (unintentional injury [UI] group: 78.8% uninsured vs 88.7% insured [adjusted odds ratio {AOR}, 0.47; 95% confidence interval {CI}, 0.43-0.51]; new chronic condition [NCC] group: 81.7% uninsured vs 91.5% insured [AOR, 0.45; 95% CI, 0.40-0.50]) and more likely not to have received any recommended follow-up care (UI group: 19.3% uninsured vs 9.2% insured [AOR, 2.59; 95% CI, 2.15-3.11]; NCC group: 9.4% uninsured vs 4.4% insured [AOR, 1.65; 95% CI, 1.32-2.06]). Based on the AORs, uninsured individuals with UIs had fewer outpatient visits (6.1% uninsured vs 9.0% insured; AOR, 0.71 [95% CI, 0.63-0.80]), office-based visits (41.8% uninsured vs 57.3% insured; AOR, 0.59 [95% CI, 0.56-0.62]), and prescription medicines (35.5% uninsured vs 35.6% insured; AOR, 0.71 [95% CI, 0.67 0.75]). Uninsured individuals with an NCC had fewer office-based visits (58.9% uninsured vs 68.3% insured; AOR, 0.77 [95% CI, 0.72-0.82]) and prescription medicines (52.7% uninsured vs 61.7% insured; AOR, 0.66 [95% CI, 0.57-0.76]). Higher proportions of uninsured individuals reported a decrease in health status (classified as much worse) approximately 3.5 months after the health shock (UI group: 9.8% uninsured vs 6.7% insured; AOR, 0.86 [95% CI, 0.75-0.98]; NCC group: 12.3% uninsured vs 10.1% insured; AOR, 0.74 [95% CI, 0.68-0.80]). Uninsured individuals with UIs were more likely to report not being fully recovered and no longer receiving treatment. At approximately 7 months after the health shock, uninsured individuals with NCCs still reported worse health status. CONCLUSIONS: Among individuals who experienced a health shock caused by an unintentional injury or a new chronic condition, uninsured individuals reported receiving less medical care and poorer short-term changes in health than those with insurance. PMID- 17356029 TI - Trends in emergency Medicaid expenditures for recent and undocumented immigrants. AB - CONTEXT: Undocumented immigrants and legal immigrants who have been in the United States less than 5 years are excluded from Medicaid eligibility, with the exception of limited coverage for emergency conditions (Emergency Medicaid). New immigrant population growth has been rapid in recent years, but little is known about use of health services by this group or the conditions for which Emergency Medicaid coverage has been applied. OBJECTIVE: To describe Emergency Medicaid use by recent and undocumented immigrants including patient characteristics, diagnoses, and recent spending trends in North Carolina, a state with a rapidly increasing population of undocumented immigrants. DESIGN, SETTING, AND PATIENTS: Descriptive analysis of North Carolina Medicaid administrative data for all claims reimbursed under Emergency Medicaid eligibility criteria 2001 through 2004 in North Carolina, a state with high immigration from Mexico and Latin America. Patients are recent and undocumented immigrants who meet categorical and income criteria for Medicaid coverage, but are excluded from full coverage due to legal status. MAIN OUTCOME MEASURES: Patient characteristics, hospitalizations, diagnoses, and Medicaid spending for emergency care. RESULTS: A total of 48,391 individuals received services reimbursed under Emergency Medicaid during the 4 year period of this study. The patient population was 99% undocumented, 93% Hispanic, 95% female, and 89% in the 18- to 40-year age group. Total spending increased by 28% from 2001 through 2004, with more rapid spending increases among elderly (98%) and disabled (82%) patients. In 2004, childbirth and complications of pregnancy accounted for 82% of spending and 91% of hospitalizations. Injury, renal failure, gastrointestinal disease, and cardiovascular conditions were also prevalent. CONCLUSIONS: Childbirth and complications of pregnancy account for the majority of Emergency Medicaid spending for undocumented immigrants in North Carolina. Spending for elderly and disabled patients, however, is increasing at a faster rate. Among nonpregnant immigrants, injuries, other acute emergencies, and severe complications of chronic disease are major contributors to Emergency Medicaid use. PMID- 17356030 TI - Emergency department use and subsequent hospitalizations among members of a high deductible health plan. AB - CONTEXT: Patients evaluated at emergency departments often present with nonemergency conditions that can be treated in other clinical settings. High deductible health plans have been promoted as a means of reducing overutilization but could also be related to worse outcomes if patients defer necessary care. OBJECTIVES: To determine the relationship between transition to a high-deductible health plan and emergency department use for low- and high-severity conditions and to examine changes in subsequent hospitalizations. DESIGN, SETTING, AND PARTICIPANTS: Analysis of emergency department visits and subsequent hospitalizations among 8724 individuals for 1 year before and after their employers mandated a switch from a traditional health maintenance organization plan to a high-deductible health plan, compared with 59 557 contemporaneous controls who remained in the traditional plan. All persons were aged 1 to 64 years and insured by a Massachusetts health plan between March 1, 2001, and June 30, 2005. MAIN OUTCOME MEASURES: Rates of first and repeat emergency department visits classified as low, indeterminate, or high severity during the baseline and follow-up periods, as well as rates of inpatient admission after emergency department visits. RESULTS: Between the baseline and follow-up periods, emergency department visits among members who switched to high-deductible coverage decreased from 197.5 to 178.1 per 1000 members, while visits among controls remained at approximately 220 per 1000 (-10.0% adjusted difference in difference; 95% confidence interval [CI], -16.6% to -2.8%; P = .007). The high-deductible plan was not associated with a change in the rate of first visits occurring during the study period (-4.1% adjusted difference in difference; 95% CI, -11.8% to 4.3%). Repeat visits in the high-deductible group decreased from 334.6 to 255.3 visits per 1000 members and increased from 321.1 to 334.4 per 1000 members in controls (-24.9% difference in difference; 95% CI, -37.5% to -9.7%; P = .002). Low-severity repeat emergency department visits decreased in the high-deductible group from 142.5 to 92.1 per 1000 members and increased in controls from 128.0 to 132.5 visits per 1000 members (-36.4% adjusted difference in difference; 95% CI, 51.1% to -17.2%; P<.001), whereas a small decrease in high-severity visits in the high-deductible group could not be excluded. The percentage of patients admitted from the emergency department in the high-deductible group decreased from 11.8 % to 10.9% and increased from 11.9% to 13.6% among controls (-24.7% adjusted difference in difference; 95% CI, -41.0% to -3.9%; P = .02). CONCLUSIONS: Traditional health plan members who switched to high-deductible coverage visited the emergency department less frequently than controls, with reductions occurring primarily in repeat visits for conditions that were not classified as high severity, and had decreases in the rate of hospitalizations from the emergency department. Further research is needed to determine long-term health care utilization patterns under high-deductible coverage and to assess risks and benefits related to clinical outcomes. PMID- 17356031 TI - How physicians can change the future of health care. AB - Today's preoccupation with cost shifting and cost reduction undermines physicians and patients. Instead, health care reform must focus on improving health and health care value for patients. We propose a strategy for reform that is market based but physician led. Physician leadership is essential. Improving the value of health care is something only medical teams can do. The right kind of competition--competition to improve results--will drive dramatic improvement. With such positive-sum competition, patients will receive better care, physicians will be rewarded for excellence, and costs will be contained. Physicians can lead this change and return the practice of medicine to its appropriate focus: enabling health and effective care. Three principles should guide this change: (1) the goal is value for patients, (2) medical practice should be organized around medical conditions and care cycles, and (3) results--risk-adjusted outcomes and costs--must be measured. Following these principles, professional satisfaction will increase and current pressures on physicians will decrease. If physicians fail to lead these changes, they will inevitably face ever-increasing administrative control of medicine. Improving health and health care value for patients is the only real solution. Value-based competition on results provides a path for reform that recognizes the role of health professionals at the heart of the system. PMID- 17356032 TI - State-federal partnerships for access to care: an end and a means. PMID- 17356033 TI - Universal health care coverage: a potential hybrid solution. PMID- 17356034 TI - Health disparities and access to health. PMID- 17356035 TI - Structural impairments that limit access to health care for patients with disabilities. PMID- 17356036 TI - High-deductible health plans and emergency department use. PMID- 17356037 TI - Access to care as a component of health system reform. PMID- 17356038 TI - JAMA patient page. Health care insurance: the basics. PMID- 17356039 TI - Survival after liver transplantation in the United Kingdom and Ireland compared with the United States. AB - BACKGROUND AND OBJECTIVE: Surgical mortality in the US is widely perceived to be superior to that in the UK. However, previous comparisons of surgical outcome in the two countries have often failed to take sufficient account of case-mix or examine long-term outcome. The standardised nature of liver transplantation practice makes it uniquely placed for undertaking reliable international comparisons of surgical outcome. The objective of this study is to undertake a risk-adjusted disease-specific comparison of both short- and long-term survival of liver transplant recipients in the UK and Ireland with that in the US. METHODS: A multicentre cohort study using two high quality national databases including all adults who underwent a first single organ liver transplant in the UK and Ireland (n = 5925) and the US (n = 41,866) between March 1994 and March 2005. The main outcome measures were post-transplant mortality during the first 90 days, 90 days to 1 year and beyond the first year, adjusted for recipient and donor characteristics. RESULTS: Risk-adjusted mortality in the UK and Ireland was generally higher than in the US during the first 90 days (HR 1.17; 95% CI 1.07 to 1.29), both for patients transplanted for acute liver failure (HR 1.27; 95% CI 1.01 to 1.60) and those transplanted for chronic liver disease (HR 1.18; 95% CI 1.07 to 1.31). Between 90 days and 1 year post-transplantation, no statistically significant differences in overall risk-adjusted mortality were noted between the two cohorts. Survivors of the first post-transplant year in the UK and Ireland had lower overall risk-adjusted mortality than those transplanted in the US (HR 0.88; 95% CI 0.81 to 0.96). This difference was observed among patients transplanted for chronic liver disease (HR 0.88; 95% CI 0.81 to 0.96), but not those transplanted for acute liver failure (HR 1.02; 95% CI 0.70 to 1.50). CONCLUSIONS: Whilst risk-adjusted mortality is higher in the UK and Ireland during the first 90 days following liver transplantation, it is higher in the US among those liver transplant recipients who survived the first post-transplant year. Our results are consistent with the notion that the US has superior acute perioperative care whereas the UK appears to provide better quality chronic care following liver transplantation surgery. PMID- 17356040 TI - Randomised, double blind, placebo controlled trial of intravenous antioxidant (n acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis. AB - BACKGROUND: Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. METHODS: We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty-three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE-II score and hospital site, and delivered groups that were similar at baseline. RESULTS: Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. CONCLUSIONS: This study provides no evidence to justify continued use of n-acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. PMID- 17356041 TI - Non-alcoholic fatty liver disease in patients with HCV genotype 4. PMID- 17356042 TI - Relative potencies of anastrozole and letrozole to suppress estradiol in breast cancer patients undergoing ovarian stimulation before in vitro fertilization. AB - CONTEXT: Breast cancer patients undergoing controlled ovarian hyperstimulation (COH) for embryo or oocyte cryopreservation should be induced by the method that leads to the least increase in estradiol (E(2)) levels. OBJECTIVE: The aim of the study was to determine the potency of anastrozole to suppress serum E(2) levels in breast cancer patients undergoing COH. DESIGN AND SETTING: A prospective sequential cohort study was conducted in an academic center for reproductive medicine between May 2003 and November 2005 for letrozole and between December 2005 and April 2006 for anastrozole. PATIENTS: Breast cancer patients presenting for fertility preservation participated in the study. INTERVENTION: COH using FSH and letrozole (n = 47) or anastrozole (n = 7) was followed by oocyte retrieval and embryo cryopreservation. MAIN OUTCOME MEASURES: Serum E(2) levels, area under the curve for E(2), and outcomes of COH cycles were measured. RESULTS: There were no significant differences between the two groups regarding length of stimulation, total gonadotropin dose, number of follicles larger than 17 mm, and the lead follicle size on human chorionic gonadotropin (hCG) day and number of embryos cryopreserved. The mean E(2) levels on the day of hCG and post-hCG days were higher in the anastrozole group compared to the letrozole group (1325.89 +/- 833.17 and 2515.07 +/- 1368.52 vs. 427.78 +/- 278.24 and 714.38 +/- 440.83 pg.d/ml; P < or = 0.01), respectively, even when anastrozole dose was increased up to 10 mg/d. The mean area under the curve was significantly higher in the anastrozole group compared to the letrozole group (4402.93 +/- 1526.7 vs. 1287.48 +/- 732.17 pg.d/ml; P <0.004). CONCLUSIONS: Breast cancer patients who underwent ovarian stimulation with anastrozole had a significantly higher exposure to E(2) than those who were stimulated with letrozole. PMID- 17356044 TI - Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa. AB - BACKGROUND: Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Adipokines and insulin play an important role in bone metabolism in healthy individuals. However, their association with bone metabolism in AN is unknown. OBJECTIVE: The aim of the study was to determine whether adipokines and insulin are independently associated with measures of BMD in adolescents with AN and controls. DESIGN/METHODS: Levels of adiponectin and insulin, fasting and after oral glucose, were evaluated in 17 AN patients and 19 controls (age, 12-18 yr), in whom hormonal parameters [GH, IGF-I, cortisol, estradiol, leptin, ghrelin, and peptide YY (PYY)] had been previously determined. Body composition, bone mineral content, and BMD at the lumbar spine, hip, femoral neck, and total body were assessed by dual energy x-ray absorptiometry. Two bone formation and bone resorption markers were examined. SETTING: The study was conducted at a General Clinical Research Center. RESULTS: Adiponectin differed between AN subjects and controls after controlling for fat mass and decreased in both after oral glucose (P = 0.02 and 0.07). On regression modeling, independent associations were observed of: 1) body mass index and adiponectin with lumbar spine bone mineral apparent density Z-scores (r(2) = 0.45); 2) lean mass, PYY, and ghrelin with hip Z-scores (r(2) = 0.55); 3) adiponectin and lean mass with femoral neck-bone mineral apparent density Z-scores (r(2) = 0.34); and 4) lean mass, PYY, GH, and ghrelin with total body-bone mineral content/height Z-scores (r(2) = 0.64), for the combined group. Adiponectin was also independently associated with BMD, and insulin was associated with bone turnover markers in the groups considered separately. CONCLUSIONS: Adiponectin contributes significantly to the variability of bone density, and insulin contributes to bone turnover markers in adolescent girls. PMID- 17356043 TI - Insulin growth factor-based dosing of growth hormone therapy in children: a randomized, controlled study. AB - CONTEXT: Weight-based dosing of GH is the standard of care for short children, although IGF-I is thought to be the main mediator of GH actions on growth. OBJECTIVE: The objective of the study was to test whether IGF-I levels achieved during GH therapy are determinants of the growth responses to GH treatment. DESIGN: This was a 2-yr, open-label, randomized, IGF-I concentration-controlled trial. Prepubertal short children [n = 172, mean age 7.53 yr, mean height sd score (HT-SDS) -2.64] with low IGF-I levels (mean IGF-I SDS -3.56) were randomized to receive one of two GH dose-titration arms in which GH dosage was titrated to achieve an IGF-I SDS at the mean [IGF((low)) group, n = 70] or the upper limit of the normal range [+2 SDS, IGF((high)) group, n = 68] or to a comparison group of conventional GH dose of 40 microg/kg/d (n = 34). SETTING: The study was conducted in a multicenter, outpatient setting. PRIMARY OUTCOME MEASURE: Change in HT-SDS over 2 yr was measured. RESULTS: One hundred forty seven patients completed the trial. Target IGF-I levels were achieved in the dose titration arms within 6-9 months. The changes in HT-SDS were +1.0, +1.1, and +1.6 for conventional, IGF((low)), and IGF((high)), respectively, with IGF((high)) showing significantly greater linear growth response (P < 0.001, compared with the other two groups). The IGF((high)) arm required higher doses (>2.5 times) than the IGF((low)) arm, and these GH doses were highly variable (20-346 microg/kg/d). Multivariate analyses suggested that the rise in the IGF-I SDS significantly impacted height outcome along with the GH dose and the pretreatment peak-stimulated GH level. CONCLUSION: IGF-I-based GH dosing is clinically feasible and allows maintaining serum IGF-I concentrations within the desired target range. Titrating the GH dose to achieve higher IGF-I targets results in improved growth responses, although at higher average GH doses. PMID- 17356045 TI - The application of the combined corticotropin-releasing hormone plus desmopressin stimulation during petrosal sinus sampling is both sensitive and specific in differentiating patients with Cushing's disease from patients with the occult ectopic adrenocorticotropin syndrome. AB - CONTEXT: Although bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation is the most accurate procedure for the differential diagnosis of ACTH dependent Cushing's syndrome (CS), 4-15% of patients with Cushing's disease (CD) fail to demonstrate diagnostic gradients. Preliminary data suggest that a more potent stimulation by the combined administration of CRH plus desmopressin during BIPSS may provide some diagnostic advantage. A crucial issue, however, is whether such an amplified stimulation may affect the specificity of the procedure, and this was the main aim of the present study. OBJECTIVE: We investigated the diagnostic accuracy of BIPSS performed by CRH plus desmopressin stimulation. DESIGN AND SETTING: A retrospective analysis was conducted at a single tertiary care center. PARTICIPANTS: Fifty-four patients were admitted for the investigation of ACTH-dependent CS. CD was diagnosed in 47 patients; occult ectopic ACTH syndrome (oEAS) was histologically confirmed in seven patients. INTERVENTION(S): All patients underwent BIPSS with CRH plus desmopressin administration. Additional noninvasive tests included CRH test, high-dose dexamethasone suppression test, desmopressin test, and pituitary magnetic resonance imaging. MAIN OUTCOME MEASURES: Gradients of inferior petrosal sinus (IPS) to peripheral (IPS/P) ACTH were calculated before and after stimulation with CRH plus desmopressin. RESULTS: The sensitivity for a basal IPS/P gradient greater than 2 was 61.7%, with 100% specificity and a diagnostic accuracy of 66.7%. After stimulation with CRH plus desmopressin, receiver operating characteristic (ROC) curve analysis showed that a cutoff gradient of more than 2 offers the best test performance. In total, 46 of 47 patients with CD had an IPS/P gradient greater than 2, but none of the patients with oEAS, resulting in a sensitivity of 97.9%. The specificity was 100%, diagnostic accuracy was 98.2%, and the positive and negative predictive values were 100 and 87.5%, respectively. A subgroup of 18 patients (16 with CD and two with oEAS) had contradictory responses to routine tests with CRH and/or high-dose dexamethasone suppression test; sensitivity, specificity, and accuracy of BIPSS in this subgroup were 100%. CONCLUSIONS: The application of a combined stimulation with CRH plus desmopressin during BIPSS is associated with a high sensitivity but no loss of specificity. PMID- 17356046 TI - Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine. AB - CONTEXT: T(3) action in neurons is essential for brain development. Recent evidence indicates that monocarboxylate transporter 8 (MCT8) is important for neuronal T(3) uptake. Hemizygous mutations have been identified in the X-linked MCT8 gene in boys with severe psychomotor retardation and elevated serum T(3) levels. OBJECTIVE: The objective of this study was to determine the functional consequences of MCT8 mutations regarding transport of T(3). DESIGN: MCT8 function was studied in wild-type or mutant MCT8-transfected JEG3 cells by analyzing: 1) T(3) uptake, 2) T(3) metabolism in cells cotransfected with human type 3 deiodinase, 3) immunoblotting, and 4) immunocytochemistry. RESULTS: The mutations identified in MCT8 comprise four deletions (24.5 kb, 2.4 kb, 14 bp, and 3 bp), three missense mutations (Ala224Val, Arg271His, and Leu471Pro), a nonsense mutation (Arg245stop), and a splice site mutation (94 amino acid deletion). All tested mutants were inactive in uptake and metabolism assays, except MCT8 Arg271His, which showed approximately 20% activity vs. wild-type MCT8. CONCLUSION: These findings support the hypothesis that the severe psychomotor retardation and elevated serum T(3) levels in these patients are caused by inactivation of the MCT8 transporter, preventing action and metabolism of T(3) in central neurons. PMID- 17356047 TI - Dysregulation of placental endothelial lipase and lipoprotein lipase in intrauterine growth-restricted pregnancies. AB - CONTEXT: Fetal supply of maternally derived fatty acids requires lipase-mediated hydrolysis of lipoprotein-borne triglycerides and phospholipids at the placental surface. OBJECTIVE: The objective of the study was to test the hypothesis that members of the triglyceride lipase gene (TLG) family are expressed in the human placenta at the maternoplacental (syncytiotrophoblast) and fetoplacental (endothelial cells) interface and that their expression is altered in pregnancy pathologies. DESIGN AND SETTING: Expression of TLG family members in primary placental cells (trophoblast and endothelial cells) and tissues of first trimester and term human placenta was analyzed by microarrays, RT-PCR, Western blotting, and immunohistochemistry. Their expression was compared between normal pregnancies and those complicated with intrauterine growth restriction (IUGR). PARTICIPANTS: Participants included women with uncomplicated pregnancies and pregnancies complicated by IUGR. RESULTS: Endothelial lipase (EL) and lipoprotein lipase (LPL) were the only lipases among the TLG family expressed in key cells of the human placenta. In first trimester, EL and LPL were expressed in trophoblasts. At term, EL was detected in trophoblasts and endothelial cells, whereas LPL was absent in these cells. Both lipases were found at placental blood vessels, EL in vascular endothelial cells and LPL in the surrounding smooth muscle cells. In total placental tissue EL expression prevails in first trimester and at term. Compared with normal placentas, EL mRNA was decreased (30%; P < 0.02), whereas LPL mRNA expression was increased (2.4-fold; P < 0.015) in IUGR. CONCLUSION: EL is the predominant TLG family member in the human placenta present at both interfaces. EL and LPL are dysregulated in IUGR. PMID- 17356048 TI - Evaluating the roles of follicle-stimulating hormone receptor polymorphisms in gonadal hyperstimulation associated with severe juvenile primary hypothyroidism. AB - CONTEXT: Rare activating mutations of the human (h)FSHR have been reported in some women with spontaneous ovarian hyperstimulation in pregnancy, where follicular growth is inappropriately stimulated by elevated concentrations of human chorionic gonadotropin acting through the hFSHR. It is not known whether ovarian hyperstimulation in peripubertal girls with untreated primary hypothyroidism is caused by hFSHR mutations and/or influenced by hFSHR allelic variants, rendering the hFSHR more sensitive to circulating TSH. OBJECTIVE: The aim of the study was to determine whether mutations of the hFSHR and/or hFSHR allelic variants are associated with greater sensitivity of the hFSHR to TSH. DESIGN: The hFSHR gene was sequenced from eight pediatric patients displaying gonadal hyperstimulation due to primary hypothyroidism. HEK293 cells expressing different hFSHR allelic combinations were studied for their responsiveness to recombinant (r)hTSH. SETTING: The study was conducted at university research centers. PATIENTS: Eight unrelated patients (seven girls and one boy) who exhibited primary hypothyroidism and gonadal hyperstimulation were included in the study. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: DNA sequencing of the hFSHR gene was the main outcome measure. Basal, rhFSHR- and rhTSH receptor-stimulated cAMP levels were assayed in HEK293 cells transfected with the hTSH receptor or different hFSHR allelic combinations. Cell surface receptor numbers were also determined. RESULTS: No hFSHR mutations were identified in the patient population, but we did identify two known polymorphisms. In vitro experiments demonstrated a dose-dependent and specific rhTSH-dependent increase in cAMP production in HEK293 cells expressing the wild type hFSHR, regardless of hFSHR isoform. CONCLUSIONS: Pediatric gonadal hyperstimulation associated with severe primary hypothyroidism is likely due to the actions of the elevated concentrations of TSH on the wild-type hFSHR, and this response is not dependent upon the hFSHR isoform. PMID- 17356049 TI - Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population. AB - BACKGROUND: Apolipoprotein A5 (APOA5) plays an important role in plasma triacylglycerol (TG) homeostasis. Five polymorphisms (1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, and c.1259T>C) in the APOA5 gene define three common haplotypes (APOA5*1, APOA5*2, and APOA5*3) in Caucasian individuals. Our aim was to determine whether these haplotypes could modulate the postprandial response in young healthy males. DESIGN AND METHODS: Eighty-eight APO E3/3 volunteers [67 with (-1131T and 56C) APOA5*1 haplotype, 12 with (-1131C and 56C) APOA5*2 haplotype, and nine with (-1131T and 56G) APOA5*3 haplotype] underwent a fat load test consisting of the consumption of 1 g of fat per kilogram body weight and 60,000 IU vitamin A. Blood samples were taken at time 0, at every hour until the sixth hour, and at every 2.5 h until the 11th hour. Total plasma cholesterol (C) and TG, and C, TG, apolipoprotein B-100, apolipoprotein B-48, and retinyl palmitate in lipoprotein fractions were determined. RESULTS: Subjects with the APOA5*2 and APOA5*3 haplotypes had a higher area under the curve of total plasma TG (P = 0.03), large TG-rich lipoprotein (TRL)-TG (P = 0.02), small TRL-TG (P = 0.04), small TRL-C (P = 0.04), large TRL-C (P = 0.03), and small apolipoprotein B100 (P = 0.04) than subjects with the APOA5*1 haplotype. CONCLUSIONS: Our findings show that the presence of the APOA5*2 and APOA5*3 haplotypes in the APOA5 gene is associated with a higher postprandial response that could be involved in the higher risk of coronary heart disease associated with the 56G and -1131C alleles. PMID- 17356050 TI - Insulin-like factor 3: a new circulating hormone related to luteinizing hormone dependent ovarian hyperandrogenism in the polycystic ovary syndrome. AB - CONTEXT: Insulin-like factor 3 (INSL3), a member of the relaxin-insulin family, is produced in the Leydig cells and at reduced levels in ovarian theca interna cells of antra follicles as well as in the corpora lutea and ovarian stroma. Among the factors potentially involved in the stimulation of gonadal expression of INSL3, recent data obtained in rats show an important role of LH. Ovaries from most women affected by polycystic ovary syndrome (PCOS) are characterized by hyperplasia of the theca interna and of cortical stroma and by an increased number of small antral follicles, and the majority of women with PCOS, particularly normal-weight subjects, have LH levels that are above the normal range. OBJECTIVE: The objective of this study was to investigate INSL3 circulating levels in both normal-weight and overweight-obese PCOS women and the association of INSL3 with gonadotropin and androgenic pattern and with ovarian morphology. DESIGN: This was a controlled study. SETTING: The study took place at an academic hospital. PARTICIPANTS: The participants included 44 PCOS patients (22 normal-weight and 22 overweight-obese) and 44 controls comparable for age and body weight. MAIN OUTCOME MEASURES: The main outcome measures included INSL3 serum concentrations, measured by RIA, in PCOS patients and controls and their correlation with clinical and biochemical phenotype and with ovarian morphology. RESULTS: INSL3 serum concentrations were significantly higher in PCOS patients with respect to controls (P = 0.003), particularly in normal-weight (P = 0.001) but not in overweight-obese (P = 0.312) PCOS patients. INSL3 serum concentrations were positively correlated with total and free testosterone and with LH levels in all women (total testosterone, P < 0.001; free testosterone, P = 0.001; LH, P = 0.002) as well as in PCOS patients (total testosterone, P = 0.024; free testosterone, P = 0.045; LH, P = 0.049). Moreover, in the PCOS group, INSL3 levels were related to a greater 17OH-progesterone response to buserelin (P = 0.015), an index of ovarian hyperandrogenism. Finally, in PCOS women, INSL3 levels were positively correlated with ovarian follicle number (P = 0.028). CONCLUSIONS: INSL3 could be considered a new circulating hormone related to LH dependent ovarian hyperandrogenism, particularly in normal-weight PCOS women. PMID- 17356051 TI - Basal and cosyntropin-stimulated plasma cortisol concentrations, as measured by high-performance liquid chromatography, in children aged 5 months to younger than 6 years. AB - CONTEXT: Topical corticosteroids are the recommended first-line treatment for all severities of persistent asthma and moderate to severe allergic rhinitis. Potential adrenal suppression resulting from corticosteroid administration necessitates monitoring of children participating in clinical studies. Measurement of pretreatment cortisol concentrations is necessary to assess effects on adrenal function. OBJECTIVE: Plasma cortisol concentrations are assay dependent; normal reference range values must be obtained for each assay. Our objective is to provide these values for children as determined by HPLC. DESIGN AND PATIENTS: Two multicenter, randomized, double-blind, placebo-controlled studies evaluating basal and cosyntropin-stimulated morning plasma cortisol concentrations for patients aged 5 to younger than 12 months with asthma and patients aged 2 to younger than 6 yr with allergic rhinitis using HPLC were conducted. MAIN OUTCOME MEASURES: Main planned outcomes of these studies are reported elsewhere. This manuscript reports plasma cortisol concentration reference range values. RESULTS: In general, mean basal plasma cortisol concentrations (n = 177) (mean +/- sd, nmol/liter) were similar among the 5 to younger than 9 months, 9 to younger than 12 months, 2 to younger than 3 yr, 3 to younger than 4 yr, 4 to younger than 5 yr, and 5 to younger than 6 yr age groups (218 +/- 149, 281 +/- 144, 257 +/- 105, 231 +/- 83, 298 +/- 118, and 237 +/- 65, respectively) and increased to comparable levels 60 min after cosyntropin stimulation (n = 178; 622 +/- 176, 638 +/- 176, 697 +/- 99, 655 +/- 103, 662 +/- 113, and 610 +/- 68, respectively). However, patients younger than 12 months had wider ranges of basal and stimulated values. CONCLUSIONS: Basal and cosyntropin stimulated morning plasma cortisol concentrations of children aged 5 to younger than 12 months and 2 to younger than 6 yr were consistently measurable, with the large majority similar among the age groups examined, and comparable with those reported elsewhere for adults. PMID- 17356052 TI - Peroxisome proliferator-activated receptor-gamma C190S mutation causes partial lipodystrophy. AB - CONTEXT: Mutations in PPARG are associated with insulin resistance and familial partial lipodystrophy, a disease characterized by altered distribution of sc fat and symptoms of the metabolic syndrome. The encoded protein, peroxisome proliferator-activated receptor (PPAR)-gamma, plays a pivotal role in regulating lipid and glucose metabolism, the differentiation of adipocytes, and other cellular regulatory processes. OBJECTIVES: The objective of the study was to detect a novel PPARG mutation in a kindred with partial lipodystrophy and analyze the functional characteristics of the mutant protein. PATIENTS AND METHODS: In three subjects with partial lipodystrophy, one unaffected family member, and 124 unaffected subjects, PPARG was screened for mutations by direct sequencing. Body composition, laboratory abnormalities, and hepatic steatosis were assessed in each affected subject. Transcriptional activity was determined, and EMSA was performed to investigate DNA binding capacity of the mutant protein. RESULTS: We identified a PPARG mutation, C190S, causing partial lipodystrophy with metabolic alterations in three affected family members. The mutation was absent in the unaffected family member and unaffected controls. The mutation is located within zinc-finger 2 of the DNA binding domain. C190S PPARgamma has a significantly lower ability to activate a reporter gene than wild-type PPARgamma in absence and presence of rosiglitazone. A dominant-negative effect was not observed. Compared with wild-type PPARgamma, C190S PPARgamma shows a reduced capacity to bind DNA. CONCLUSION: Mutation of a zinc-binding amino acid of PPARgamma leads to an altered protein-DNA binding pattern, resulting in a partial loss of function, which in turn is associated with partial lipodystrophy. PMID- 17356053 TI - Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. AB - AIM/HYPOTHESIS: Obesity is associated with increased triacylglycerol (TAG) storage in adipose tissue and insulin resistance. The mobilization of stored TAG is mediated by hormone-sensitive lipase (HSL) and the recently discovered adipose triglyceride lipase (ATGL). The aim of the present study was to examine whether ATGL and HSL mRNA and protein expression are altered in insulin-resistant conditions. In addition, we investigated whether a possible impaired expression could be reversed by a period of weight reduction. METHODS: Adipose tissue biopsies were taken from obese subjects (n = 44) with a wide range of insulin resistance, before and just after a 10-wk hypocaloric diet. ATGL and HSL protein and mRNA expression was determined by Western blot and quantitative RT-PCR, respectively. RESULTS: Fasting insulin levels and the degree of insulin resistance (using the homeostasis model assessment index for insulin resistance) were negatively correlated with ATGL and HSL protein expression, independent of age, gender, fat cell size, and body composition. Both mRNA and protein levels of ATGL and HSL were reduced in insulin-resistant compared with insulin-sensitive subjects (P < 0.05). Weight reduction significantly decreased ATGL and HSL mRNA and protein expression. A positive correlation between the decrease in leptin and the decrease in ATGL protein level after weight reduction was observed. Finally, ATGL and HSL mRNA and protein levels seem to be highly correlated, indicating a tight coregulation and transcriptional control. CONCLUSIONS: In obese subjects, insulin resistance and hyperinsulinemia are strongly associated with ATGL and HSL mRNA and protein expression, independent of fat mass. Data on weight reduction indicated that also other factors (e.g. leptin) relate to ATGL and HSL protein expression. PMID- 17356054 TI - Heterozygosity for a mutation in the growth hormone-releasing hormone receptor gene does not influence adult stature, but affects body composition. AB - CONTEXT: Biallelic mutations in the GHRH receptor (GHRHR) gene (GHRHR) are a frequent cause of isolated GH deficiency (IGHD). Although heterozygous carriers of these mutations appear normal, we hypothesized that heterozygosity for a GHRHR mutation might be associated with a subclinical phenotype. METHODS: We studied members of a large Brazilian kindred with IGHD (Itabaianinha cohort) caused by a homozygous null GHRHR mutation. We compared 76 adult subjects (age, 25-75 yr) heterozygous for the mutation (WT/MT) with 77 sex-matched controls from the same population who are homozygous for the wild-type GHRHR allele (WT/WT). RESULTS: We found no difference in adult height and sd score for serum IGF-I between the two groups. Body weight, body mass index, skin folds, waist and hip circumferences, and lean mass were all reduced in WT/MT subjects. Percentage fat mass and waist/hip ratio were similar in the two groups. Fasting insulin and homeostasis model assessment of insulin resistance were lower in WT/MT. The other biochemical parameters [total and fractionated cholesterol, triglycerides, lipoprotein (a), and C-reactive protein] were not different between the two groups. CONCLUSIONS: Heterozygosity for a null GHRHR mutation is not associated with reduction in adult stature or in serum IGF-I but is associated with changes in body composition and possibly an increase in insulin sensitivity. These effects do not seem to be modulated by changes in circulating IGF-I. PMID- 17356055 TI - The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism. AB - CONTEXT: Estrogens regulate bone mass by binding to the estrogen receptor (ER) alpha as well as ER-beta. The specific ERalpha cofactor retinoblastoma interacting zinc finger protein (RIZ)-1 enhances ERalpha function in the presence of estrogen. OBJECTIVE: The objective of the study was to determine whether a RIZ P704 insertion (+)/deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. DESIGN: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmo OPRA Study, respectively. SETTING: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmo University Hospital, and Uppsala University Hospital. PARTICIPANTS: In total, 4058 men and women, aged 69-81 yr, were randomly selected from population registries. MAIN OUTCOME MEASURES: BMD (grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. RESULTS: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(-/-) group (r = 0.19 vs. r = 0.08, P < 0.05). CONCLUSIONS: These large-scale studies of elderly men and women indicate that the ERalpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment. PMID- 17356056 TI - Pathological features and inhaled corticosteroid response of eosinophilic and non eosinophilic asthma. AB - BACKGROUND: Non-eosinophilic asthma is a potentially important clinicopathological phenotype since there is evidence that it responds poorly to inhaled corticosteroid therapy. However, little is known about the underlying airway immunopathology and there are no data from placebo-controlled studies examining the effect of inhaled corticosteroids. METHODS: Airway immunopathology was investigated using induced sputum, bronchial biopsies, bronchial wash and bronchoalveolar lavage in 12 patients with symptomatic eosinophilic asthma, 11 patients with non-eosinophilic asthma and 10 healthy controls. The patients with non-eosinophilic asthma and 6 different patients with eosinophilic asthma entered a randomised, double-blind, placebo-controlled crossover study in which the effects of inhaled mometasone 400 microg once daily for 8 weeks on airway responsiveness and asthma quality of life were investigated. RESULTS: Patients with non-eosinophilic asthma had absence of eosinophils in the mucosa (median 4.4 cells/mm(2) vs 23 cells/mm(2) in eosinophilic asthma and 0 cells/mm(2) in normal controls; p = 0.03) and normal subepithelial layer thickness (5.8 microm vs 10.3 microm in eosinophilic asthma and 5.1 microm in controls, p = 0.002). Non eosinophilic and eosinophilic asthma groups had increased mast cell numbers in the airway smooth muscle compared with normal controls (9 vs 8 vs 0 cells/mm(2), p = 0.016). Compared with placebo, 8 weeks of treatment with inhaled mometasone led to less improvement in methacholine PC(20) (0.5 vs 5.5 doubling concentrations, 95% CI of difference 1.1 to 9.1; p = 0.018) and asthma quality of life (0.2 vs 1.0 points, 95% CI of difference 0.27 to 1.43; p = 0.008). CONCLUSIONS: Non-eosinophilic asthma represents a pathologically distinct disease phenotype which is characterised by the absence of airway eosinophilia, normal subepithelial layer thickness and a poor short-term response to treatment with inhaled corticosteroids. PMID- 17356057 TI - Association of maternal smoking with increased infant oxidative stress at 3 months of age. AB - BACKGROUND: Cigarette smoke is a major source of free radicals and oxidative stress. With a significant proportion of women still smoking during pregnancy, this common and avoidable exposure has the potential to influence infant oxidative status, which is implicated in the increased propensity for airway inflammation and asthma. The aim of this study was to examine the effects of maternal smoking on markers of infant oxidative stress. METHODS: The level of oxidative stress (using urinary F2-isoprostanes as a marker of lipid peroxidation) was compared in infants of smokers (n = 33) and non-smokers (n = 54) at 3 months of age. These groups were balanced for maternal atopy and socioeconomic status. Infant urinary cotinine levels were also measured as an indicator of early postnatal cigarette smoke exposure. RESULTS: Maternal smoking was associated with significantly higher infant cotinine levels, despite the fact that most smoking mothers (83.8%) claimed not to smoke near their baby. Maternal smoking was associated with significantly higher markers of oxidative stress (F2 isoprostane) at 3 months of age. There was also a positive correlation between urinary F2-isoprostanes and infant urinary cotinine levels. CONCLUSIONS: Although this study does not separate the prenatal and postnatal effects of smoking, these findings indicate that environmental tobacco smoke in the early postnatal period adversely affects pro-oxidative/antioxidative status within weeks of life in very early infancy. PMID- 17356058 TI - The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor. AB - BACKGROUND: The alveolar compartment is a procoagulant antifibrinolytic environment in acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A study was undertaken to test the hypothesis that the alveolar epithelium can initiate intra-alveolar coagulation by expressing active tissue factor (TF). METHODS: Using an in vitro cell surface TF assay and TF ELISA, the activity and production of TF in cultured alveolar epithelial (A549) cells following exposure to cytomix (tumour necrosis factor alpha, interleukin 1beta and interferon gamma) was measured. TF gene transcription was measured by semi quantitative reverse-transcription PCR. Immunohistochemistry for TF was performed on lung sections from patients with ARDS and controls. TF protein levels were measured by ELISA in undiluted pulmonary oedema fluid from patients with ALI/ARDS and compared with control patients with hydrostatic pulmonary oedema. RESULTS: TF activity, mRNA and protein levels increased in A549 cells after stimulation with cytomix. Increased TF activity was also seen in A549 cells following incubation with pulmonary oedema fluid from patients with ALI/ARDS. Immunohistochemistry for TF in human lung tissue from patients with ARDS showed prominent TF staining in alveolar epithelial cells as well as intra-alveolar macrophages and hyaline membranes. TF antigen levels in oedema fluid (median 37 113 (IQR 14 956-73 525) pg/ml) were significantly higher than in plasma (median 336 (IQR 165-669) pg/ml, p<0.001) in patients with ALI/ARDS, and TF procoagulant activity in oedema fluid was much higher than in plasma of these patients. Higher plasma levels were associated with mortality. CONCLUSIONS: The alveolar epithelium is capable of modulating intra-alveolar coagulation through upregulation of TF following exposure to inflammatory stimuli and may contribute to intra-alveolar fibrin deposition in ARDS. PMID- 17356059 TI - Profiling serum biomarkers in patients with COPD: associations with clinical parameters. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with significant systemic consequences. Recognition of the systemic manifestations has stimulated interest in identifying circulating biomarkers in these patients. A systematic analysis was undertaken of multiple protein analytes in the serum of well characterised patients with COPD and matched controls using novel protein microarray platform (PMP) technology. METHODS: Forty-eight patients (65% men) with COPD (forced expiratory volume in 1 s <55%) and 48 matched controls were studied. Anthropometric parameters, pulmonary function tests, 6-minute walk distance, the BODE index and the number of exacerbations were measured and the association of these outcomes with the baseline levels of 143 serum biomarkers measured by PMP was explored. RESULTS: Thirty biomarker clusters were identified and ranked by computing the predictive value of each cluster for COPD (partial least squares discriminant analysis). From the 19 best predictive clusters, 2-3 biomarkers were selected based on their pathophysiological profile (chemoattractants, inflammation, tissue destruction and repair) and the statistical significance of their relationship with clinically important end points was tested. The selected panel of 24 biomarkers correlated (p<0.01) with forced expiratory volume in 1 s, carbon monoxide transfer factor, 6-minute walk distance, BODE index and exacerbation frequency. CONCLUSION: PMP technology can be useful in identifying potential biomarkers in patients with COPD. Panels of selected serum markers are associated with important clinical predictors of outcome in these patients. PMID- 17356060 TI - Soluble mesothelin in effusions: a useful tool for the diagnosis of malignant mesothelioma. AB - BACKGROUND: The diagnosis of malignant mesothelioma is frequently difficult, the most common differential diagnosis being reactive pleural conditions and metastatic adenocarcinoma. Soluble mesothelin levels in serum have recently been shown to be highly specific and moderately sensitive for mesothelioma. As most patients with mesothelioma present with exudative effusions of either the pleura or the peritoneum, a study was undertaken to determine if levels of mesothelin were raised in these fluids and if the increased levels could help to distinguish mesothelioma from other causes of exudative effusion. METHODS: Pleural fluid was collected from 192 patients who presented to respiratory clinics (52 with malignant mesothelioma, 56 with non-mesotheliomatous malignancies and 84 with effusions of non-neoplastic origin). Peritoneal fluid was collected from 42 patients (7 with mesothelioma, 14 with non-mesotheliomatous malignancies and 21 with benign effusions). Mesothelin levels were determined in effusion and serum samples by ELISA. RESULTS: Significantly higher levels of mesothelin were found in effusions of patients with mesothelioma; with a specificity of 98%, the assay had a sensitivity of 67% comparing patients with mesothelioma and those with effusions of non-neoplastic origin. In 7 out of 10 cases mesothelin levels were raised in the effusion collected 3 weeks to 10 months before the diagnosis of mesothelioma was made; in 4 out of 8 of these, mesothelin levels were increased in the effusion but not in the serum. CONCLUSIONS: Measurement of mesothelin concentrations in the pleural and/or peritoneal effusion of patients may aid in the differential diagnosis of mesothelioma in patients presenting with effusions. PMID- 17356061 TI - Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. AB - OBJECTIVES: The aim of the study was to determine whether mutations at RT codon 208 are associated with nucleoside RT inhibitor (NRTI) exposure, NRTI resistance patterns and HIV-1 subtype. METHODS: Six thousand three hundred and fifty two genotypic resistance tests linked to a clinical database were analysed. RESULTS: The prevalence of mutations at codon 208 was 6/2347 (0.3%) in treatment-naive and 165/4005 (4.1%) in treatment-experienced persons. H208Y was the most common mutation in both groups (0.2% and 3.8%, respectively) and occurred in 4.5% of treatment-experienced persons with Subtype B, 1.7% of those with Subtype C and 0.7% of those with other non-B subtypes (P=0.001). The association with subtypes was independent of treatment experience. H208Y showed a strong association with NRTI experience, which persisted after adjusting for subtype [odds ratio (OR) 19.34; 95% confidence interval (CI) 7.87-47.54; P=0.0001]. The prevalence of H208Y was highest in genotypes harbouring M184V and the thymidine analogue mutations (TAMs) M41L, D67N, L210W and T215Y. The median number of TAMs was 4 and 0 in genotypes with and without H208Y, respectively (P=0.0001). The prevalence of H208Y declined over time, being highest in 1998 (9.9%) and lowest in 2003 (0.9%) (P=0.0001). CONCLUSIONS: There is a strong association between H208Y and NRTI experience, particularly in persons with Subtype B harbouring multiple NRTI resistance mutations. These findings indicate an accessory role for H208Y in NRTI resistance. PMID- 17356062 TI - The isolated MUC5AC gene product from human ocular mucin displays intramolecular conformational heterogeneity. AB - Atomic force microscopy (AFM) has been used to show that human ocular mucins contain at least three distinct polymer conformations, separable by isopycnic density gradient centrifugation. In this work we have used affinity purification against the anti(mucin peptide core) monoclonal antibody 45M1 to isolate MUC5AC gene products, a major component of human ocular mucins. AFM images confirm that the affinity-purified polymers adopt distinct conformations that coidentify with two of those observed in the parent population, and further reveal that these two different conformations can be present within the same polymer. AFM images of the complexes formed after incubation of 45M1 with the parent sample reveal different rates of binding to the two MUC5AC polymer types. The variability of gene products within a mucin population was revealed by analyzing the height distributions along the polymer contour and periodicities in distances between occupied antibody binding sites. AFM analysis of mucin polymers at the single molecule level provides new information about the genetic origins of individual polymers and the contributions of glycosylation to the physicochemical properties of mucins, which can be correlated with information obtained from biochemistry, antibody binding assays, and molecular biology techniques. PMID- 17356063 TI - Microtubule-targeting-dependent reorganization of filopodia. AB - Interaction between the microtubule system and actin cytoskeleton has emerged as a fundamental process required for spatial regulation of cell protrusion and retraction activities. In our current studies, analysis of digital fluorescence images revealed targeting of microtubules to filopodia in B16F1 melanoma cells and fibroblasts. We investigated the functional consequence of targeting on filopodia reorganization and examined mechanisms by which microtubules may be guided to, or interact with, filopodia. Live cell imaging studies show that targeting events in lamellipodia wings temporally correlated with filopodia turning toward the lamellipodium midline and with filopodia merging. Rapid uncoupling of targeting with nocodazole decreased filopodia merging events and increased filopodia density. Total internal reflection fluorescence microscopy identified microtubules near the ventral surface and upward movement of targeted filopodia. The role of adhesion sites and microtubule plus-end proteins in targeting was investigated. Correlation of adhesion sites with microtubule targeting to filopodia was not observed and depletion of microtubule plus-end proteins did not significantly alter targeting frequency. We propose that microtubules target filopodia, independent of focal adhesions and plus-end proteins, causing filopodia movement and microtubules regulate filopodia density in lamellipodia wings through filopodia merging events. PMID- 17356064 TI - Aurora B controls the association of condensin I but not condensin II with mitotic chromosomes. AB - The assembly of mitotic chromosomes is controlled by condensin complexes. In vertebrates, condensin I binds to chromatin in prometaphase, confers rigidity to chromosomes and enables the release of cohesin complexes from chromosome arms, whereas condensin II associates with chromosomes in prophase and promotes their condensation. Both complexes are essential for chromosome segregation in anaphase. Although the association of condensins with chromatin is important for the assembly and segregation of mitotic chromosomes, it is poorly understood how this process is controlled. Here we show that the mitotic kinase Aurora B regulates the association of condensin I, but not the interaction of condensin II with chromatin. Quantitative time-lapse imaging of cells expressing GFP-tagged condensin subunits revealed that Aurora B is required for efficient loading of condensin I onto chromosomes in prometaphase and for maintenance of the complex on chromosomes in later stages of mitosis. The three non-SMC subunits of condensin I are Aurora B substrates in vitro and their mitosis-specific phosphorylation depends on Aurora B in vivo. Our data indicate that Aurora B contributes to chromosome rigidity and segregation by promoting the binding of condensin I to chromatin. We have also addressed how Aurora B might mediate the dissociation of cohesin from chromosome arms. PMID- 17356065 TI - Modulation of Nod2-dependent NF-kappaB signaling by the actin cytoskeleton. AB - Actin disruption by CytochalasinD (CytD) and LatrunculinB (LatB) induced NF kappaB activation in myelomonocytic and intestinal epithelial cells. In an attempt to elucidate the mechanism by which actin disruption induced IKK activation, we studied the human Nod2 protein, which was able to induce NF-kappaB activation and whose expression was restricted to myelomonocytic and intestinal epithelial cells. Nod2 is thought to play key roles in pathogen defence through sensing bacteria and generating an inflammatory immune response. We showed that actin disruption by CytD significantly and specifically increased Nod2-mediated NF-kappaB signaling. Nod2 was fully partitioned in the Triton-X-100-insoluble fraction but translocated into the soluble fraction after CytD treatment, demonstrating that the presence of Nod2 in the detergent-insoluble pellet was specific to actin cytoskeleton. Confocal analysis also revealed a Nod2 colocalization with membrane-associated F-actin. Colocalization and co immunoprecipitation assays with endogenous Rac1 have shown that Nod2 associated with activated Rac1 in membrane ruffles through both its N-terminal caspase recruitment domains (CARD) and C-terminal leucine-rich repeats (LRRs). Membrane ruffle disruption by a Rac1 dominant negative form primed Nod2-dependent NF kappaB signaling. The recruitment of Nod2 in Rac-induced dynamic cytoskeletal structures could be a strategy to both repress the Nod2-dependent NF-kappaB signaling in unstimulated cells and rapidly mobilize Nod2 during bacterial infection. PMID- 17356066 TI - Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks. AB - Immature astrocytes and astrocytoma cells contain synemin and three other intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), vimentin and nestin. Here, we show that, after neurotrauma, reactive astrocytes produce synemin and thus propose synemin as a new marker of reactive astrocytes. Comparison of synemin mRNA and protein levels in brain tissues and astrocyte cultures from wild-type, Vim(-)(/)(-) and Gfap(-)(/)(-)Vim(-)(/)(-) mice showed that in the absence of vimentin, synemin protein was undetectable although synemin mRNA was present at wild-type levels. By contrast, in Gfap(-)(/)(-) astrocytes, synemin protein and mRNA levels, as well as synemin incorporation into vimentin IFs, were unaltered. Biochemical assays with purified proteins suggested that synemin interacts with GFAP IFs like an IF-associated protein rather than like a polymerization partner, whereas the opposite was true for synemin interaction with vimentin. In transfection experiments, synemin did not incorporate into normal, filamentous GFAP networks, but integrated into vimentin and GFAP heteropolymeric networks. Thus, alongside GFAP, vimentin and nestin, reactive astrocytes contain synemin, whose accumulation is suppressed post transcriptionally in the absence of a polymerization partner. In astrocytes, this partner is vimentin and not GFAP, which implies a functional difference between these two type III IF proteins. PMID- 17356067 TI - Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger. AB - The prophenoloxidase-activating cascade is a key component of arthropod immunity. Drosophila prophenoloxidase is stored in crystal cells, a specialized class of blood cells from which it is released through cell rupture. Within minutes after bleeding, prophenoloxidase is activated leading to visible melanization of the clot matrix. Using crystal cell rupture and melanization as readouts to screen mutants in signal transduction pathways, we show that prophenoloxidase release requires Jun N-terminal kinase, small Rho GTPases and Eiger, the Drosophila homolog of tumor necrosis factor. We also provide evidence that in addition to microbial products, endogenous signals from dying hemocytes contribute to triggering and/or assembly of the prophenoloxidase-activating cascade, and that this process can be inhibited in vitro and in vivo using the viral apoptotic inhibitor p35. Our results provide a more comprehensive view of immune signal transduction pathways, with implications for immune reactions where cell death is used as a terminal mode of cell activation. PMID- 17356068 TI - Analogs of the Golgi complex in microsporidia: structure and avesicular mechanisms of function. AB - Microsporidia are obligatory intracellular parasites, most species of which live in the host cell cytosol. They synthesize and then transport secretory proteins from the endoplasmic reticulum to the plasma membrane for formation of the spore wall and the polar tube for cell invasion. However, microsporidia do not have a typical Golgi complex. Here, using quick-freezing cryosubstitution and chemical fixation, we demonstrate that the Golgi analogs of the microsporidia Paranosema (Antonospora) grylli and Paranosema locustae appear as 300-nm networks of thin (25- to 40-nm diameter), branching or varicose tubules that display histochemical features of a Golgi, but that do not have vesicles. Vesicles are not formed even if membrane fusion is inhibited. These tubular networks are connected to the endoplasmic reticulum, the plasma membrane and the forming polar tube, and are positive for Sec13, gammaCOP and analogs of giantin and GM130. The spore-wall and polar-tube proteins are transported from the endoplasmic reticulum to the target membranes through these tubular networks, within which they undergo concentration and glycosylation. We suggest that the intracellular transport of secreted proteins in microsporidia occurs by a progression mechanism that does not involve the participation of vesicles generated by coat proteins I and II. PMID- 17356071 TI - Clinical trial registration promotes patient protection and benefit, advances the trust of everyone, and is required. PMID- 17356069 TI - Endofin acts as a Smad anchor for receptor activation in BMP signaling. AB - Signaling through receptors of the transforming growth factor beta (TGFbeta) superfamily is mediated by cytoplasmic Smad proteins. It has been demonstrated that Smad anchor for receptor activation (SARA) facilitates TGFbeta and activin/nodal signaling by recruiting and presenting Smad2/3 to the receptor complex. SARA does not bind Smad1 and hence does not enhance bone morphogenetic protein (BMP) signaling. Here we report for the first time that the endosome associated FYVE-domain protein endofin acts as a Smad anchor for receptor activation in BMP signaling. We demonstrate that endofin binds Smad1 preferentially and enhances Smad1 phosphorylation and nuclear localization upon BMP stimulation. Silencing of endofin by RNAi resulted in a reduction in BMP dependent Smad1 phosphorylation. Moreover, disruption of the membrane-anchoring FYVE motif by point mutation led to a reduction of BMP-responsive gene expression in cell culture and Xenopus ectodermal explants. Furthermore, we demonstrate that endofin contains a protein-phosphatase-binding motif, which functions to negatively modulate BMP signals through receptor dephosphorylation. Taken together, our results suggest that endofin plays an important role in both positive and negative feedback regulation of the BMP signaling pathway. PMID- 17356072 TI - The impact of pulmonary arterial hypertension on idiopathic pulmonary fibrosis. PMID- 17356073 TI - Quantitative CT of fibrotic interstitial lung disease. PMID- 17356074 TI - On beyond zebra: understanding rare diseases. PMID- 17356076 TI - Inhaled steroids and outcomes in COPD: progressing beyond FEV1. PMID- 17356075 TI - Inspiratory efforts during mechanical ventilation: is there risk of barotrauma? PMID- 17356077 TI - Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis. AB - BACKGROUND: Pulmonary hypertension (PH) is commonly seen in patients with idiopathic pulmonary fibrosis (IPF). We sought to examine the relationship between pulmonary function tests (PFTs), including the percentage of predicted FVC (FVC%), percentage of predicted total lung capacity, percentage of predicted diffusing capacity of the lung for carbon monoxide (Dlco%), the composite physiologic index (CPI), and PH. The ability of FVC%, Dlco%, and FVC%/Dlco% ratio to predict underlying PH was assessed. METHODS: Retrospective review of IPF patients seen at a tertiary referral center over an 8-year interval in whom both PFT and right-heart catheterization data were available. RESULTS: The study cohort consisted of 118 patients, of whom 48 patients (40.7%) had PH. There was no correlation between measures of lung volumes or the CPI with underlying PH. There was a modest association between Dlco% and PH, with Dlco% < 30 having a twofold-higher prevalence of PH (56.4%) compared to Dlco% >/= 30 (28.6%). Cardiac dysfunction might have played a small role, since 16.1% of the patients had an associated elevated pulmonary capillary wedge pressure. There was a trend to a higher prevalence and greater severity of PH in those patients with FVC% > 70 compared to the group with FVC% < 40. CONCLUSION: PH is common in patients with IPF. There is a poor correlation between lung function measures and PH, suggesting that factors other than fibrosis may play a role in the etiology. The unexpected high prevalence and severity of PH in patients with well-maintained lung function have implications for the prognosis and management of the disease. PMID- 17356078 TI - Respiratory bronchiolitis-interstitial lung disease: long-term outcome. AB - BACKGROUND: The clinical and physiologic features of respiratory bronchiolitis (RB)-interstitial lung disease (ILD) have been previously described; however, the natural history and outcome have not been systematically evaluated. The majority of published reports consider RB-ILD to be a nonprogressive ILD that clinically improves with smoking cessation and antiinflammatory treatment. In this study, we sought to determine the outcome of RB-ILD patients with and without smoking cessation and with and without corticosteroid therapy. METHODS: Thirty-two RB-ILD cases confirmed by surgical lung biopsy were identified from a prospectively enrolled cohort of subjects with ILD. Initial and follow-up data on symptoms, physiology, treatment, and outcome were collected and analyzed. RESULTS: Kaplan Meier analysis revealed that at least 75% of RB-ILD patients survived > 7 years after diagnosis. Clinical improvement occurred in only 28% of cases, and physiologic improvement occurred in 10.5% of cases. One patient died of progressive ILD, and two patients died of non-small cell lung cancer. While physiologic improvement was limited to those who had ceased smoking, corticosteroids and/or other immunosuppressive therapy had little effect on symptoms or physiology. CONCLUSIONS: This study shows that prolonged survival is common in RB-ILD. However, symptomatic and physiologic improvement occurs in only a minority of patients, and neither smoking cessation nor immunosuppressive therapy is regularly associated with clinically significant benefit. PMID- 17356079 TI - Lung CT densitometry in systemic sclerosis: correlation with lung function, exercise testing, and quality of life. AB - BACKGROUND: To ascertain if analysis of lung density histograms in thin-section CT was more reproducible than visual assessment of lung changes in systemic sclerosis (SSc), and if such density histogram parameters as mean lung attenuation (MLA), skewness, and kurtosis could more closely reflect pulmonary function as well as exercise and quality of life impairment. METHODS: The intraoperator and interoperator reproducibility of visual and densitometric lung CT analysis in 48 SSc patients examined with CT were evaluated by means of weighted kappa statistics. Univariate and multivariate regression analyses were applied to evaluate the relationship of visual and densitometric CT measurements with functional parameters including functional residual capacity (FRC), FVC, FEV(1), diffusion capacity of the lung for carbon monoxide (Dlco), 6-min walking testing (6MWT), and health-related quality of life questionnaire (QLQ) parameters. RESULTS: The intraoperator and interoperator reproducibility of MLA (intraobserver weighted kappa = 0.97; interobserver weighted kappa = 0.96), skewness (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88), and kurtosis (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88) were higher than those of visual assessment (intraobserver weighted kappa = 0.71; interobserver weighted kappa = 0.69). In univariate analysis, only densitometric measurements were correlated with some exercise and QLQ parameters. In multivariate analysis, MLA (square regression coefficient corrected [R(2)c] = 0.70), skewness (R(2)c = 0.78), and kurtosis (R(2)c = 0.77) were predicted by FRC, FVC, Dlco, 6MWT, and QLQ parameters, while visual assessment was associated only with FRC and FVC (R(2)c = 0.40). CONCLUSIONS: In SSc, densitometric analysis is more reproducible than visual assessment of lung changes in thin-section CT and more closely correlated to pulmonary function testing, 6MWT, and QLQ. Density histogram parameters may be useful for cross-sectional and longitudinal studies of lung involvement in SSc. PMID- 17356080 TI - A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo. AB - BACKGROUND: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1). METHODS: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking. RESULTS: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers. CONCLUSIONS: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials. PMID- 17356081 TI - Tiotropium and simplified detection of dynamic hyperinflation. AB - STUDY OBJECTIVE: To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium. METHODS: IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH. RESULTS: At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/ 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003). CONCLUSION: In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium. PMID- 17356082 TI - Impact of COPD exacerbations on patient-centered outcomes. AB - BACKGROUND: Frequent exacerbations are associated with a faster decline in FEV(1), impaired health status, and worse survival. Their impact and temporal relationship with other outcomes such as functional status, dyspnea, and the multidimensional body mass index, obstruction, dyspnea, exercise capacity (BODE) index remain unknown. HYPOTHESIS: We reasoned that exacerbations affect the BODE index and its components, and that changes in the BODE index could be used to monitor the effect of exacerbations on the host. STUDY DESIGN: Prospective observational study in a Veterans Affairs medical center. METHODS: We studied 205 patients with COPD (mean [+/- SD] FEV(1), 43 +/- 15% predicted), and recorded the body mass index, FEV(1) percent predicted, modified Medical Research Council dyspnea scale, 6-min walk distance, and the BODE index at baseline, during the exacerbation, and at 6, 12, and 24 months following the first episode, and documented all exacerbations for 2 years after the first acute exacerbation. RESULTS: From the cohort, 130 patients (63%) experienced 352 exacerbations or (0.85 exacerbations per patient per year); 48 patients (23%), experienced one episode, 82 patients (40%) experienced 2 or more exacerbations, and 50 patients required hospitalization. At study entry, exacerbators had a worse mean baseline BODE index score (4.2 +/- 2.1 vs 3.57 +/- 2.3, respectively; p < 0.03). The BODE index score worsened by 1.38 points during the exacerbation, and remained 0.8 and 1.1 points above baseline at 1 and 2 years, respectively. There was little change in BODE index score at 2 years in nonexacerbators. CONCLUSION: COPD exacerbations negatively impact on the BODE index and its components. The BODE index is a sensitive tool used to assess the impact of exacerbations and to monitor COPD disease progression. PMID- 17356083 TI - Prevalence and risks of chronic airway obstruction: a population cohort study in taiwan. AB - BACKGROUND: This study investigated the prevalence, incidence, and hospitalization for chronic airway obstruction (CAO) in a population cohort. METHODS: Medical reimbursement claims from 1996 to 2002 based on a 1996 insured cohort of 167,372 persons from National Health Insurance, Taiwan, were used. We presented the chronological trends of CAO (International Classification of Diseases, Ninth Revision code 496) and the relationships between the CAO severity and age, sex, urbanization, and hospitalization and comorbidity for the population >/= 40 years old. RESULTS: The overall average annual prevalence and incidence rates were 2.48/100 and 0.66/100, respectively, for the population, among 4,568 patients with CAO cared during the study period. For the population aged >/= 70 years, the prevalence rates had a peak of 8.83/100 in 1998 and afterward remained a plateau until 2002. The corresponding incidence decreased from 2.48/100 to 1.62/100, and the hospitalization rate for them had a peak of 2.22/100 in 1999. The multivariate logistic regression analysis showed that the risk of hospitalization for CAO was higher for patients with the comorbidity of renal failure, coronary artery disease, and pneumonia and influenza, but lower with skin and joint disorders. CONCLUSIONS: The national insurance program promotes patient care and provides a proper pathway for surveillance and identification of CAO. PMID- 17356084 TI - Inspiratory muscle unloading by neurally adjusted ventilatory assist during maximal inspiratory efforts in healthy subjects. AB - BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation in which the ventilator is controlled by the electrical activity of the diaphragm (EAdi). During maximal inspirations, the pressure delivered can theoretically reach extreme levels that may cause harm to the lungs. The aims of this study were to evaluate whether NAVA could efficiently unload the respiratory muscles during maximal inspiratory efforts, and if a high level of NAVA would suppress EAdi without increasing lung-distending pressures. METHOD: In awake healthy subjects (n = 9), NAVA was applied at increasing levels in a stepwise fashion during quiet breathing and maximal inspirations. EAdi and airway pressure (Paw), esophageal pressure (Pes), and gastric pressure, flow, and volume were measured. RESULTS: During maximal inspirations with a high NAVA level, peak Paw was 37.1 +/- 11.0 cm H(2)O (mean +/- SD). This reduced Pes deflections from - 14.2 +/- 2.7 to 2.3 +/- 2.3 cm H(2)O (p < 0.001) and EAdi to 43 +/- 7% (p < 0.001), compared to maximal inspirations with no assist. At high NAVA levels, inspiratory capacity showed a modest increase of 11 +/- 11% (p = 0.024). CONCLUSION: In healthy subjects, NAVA can safely and efficiently unload the respiratory muscles during maximal inspiratory maneuvers, without failing to cycle-off ventilatory assist and without causing excessive lung distention. Despite maximal unloading of the diaphragm at high levels of NAVA, EAdi is still present and able to control the ventilator. PMID- 17356085 TI - Clinical characteristics and outcomes of obstetric patients requiring ICU admission. AB - OBJECTIVES: To review a series of critically ill obstetric patients admitted to our ICU to assess the spectrum of disease, required interventions, and fetal/maternal mortality, and to identify conditions associated with maternal death. DESIGN: Retrospective cohort. SETTING: Medical-surgical ICU in a university-affiliated hospital. PATIENTS: Pregnant/postpartum admissions between January 1, 1998, and September 30, 2005. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We studied 161 patients (age, 28 +/- 9 years; mean gestational age, 29 +/- 9 weeks) [mean +/- SD], constituting 10% of 1,571 hospital admissions. APACHE (acute physiology and chronic health evaluation) II score was 14 +/- 8, with 24% predicted mortality; sequential organ failure assessment score was 5 +/- 3; and therapeutic intervention scoring system at 24 h was 25 +/- 9. Forty-one percent of patients required mechanical ventilation (MV). ARDS, shock, and organ dysfunction were present in 19%, 25%, and 48% of patients, respectively. Most patients (63%) were admitted postpartum, and 74% of admissions were of obstetric cause. Hypertensive disease (40%), major hemorrhage (16%), septic abortion (12%), and nonobstetric sepsis (10%) were the principal diagnoses. Maternal mortality was 11%, with multiple organ dysfunction syndrome (44%) and intracranial hemorrhage (39%) as main causes. There were no differences in death rate in patients admitted for obstetric and nonobstetric causes. Fetal mortality was 32%. Only 30% of patients received antenatal care, which was more frequent in survivors (33% vs 6% nonsurvivors, p = 0.014). CONCLUSIONS: Although ARDS, organ failures, shock, and use of MV were extremely frequent in this population, maternal mortality remains within an acceptable range. APACHE II overpredicted mortality in these patients. Septic abortion is still an important modifiable cause of mortality. Efforts should concentrate in increasing antenatal care, which was clearly underprovided in these patients. PMID- 17356086 TI - Respiratory polygraphy with actigraphy in the diagnosis of sleep apnea-hypopnea syndrome. AB - OBJECTIVE: To determine the utility and reliability of a respiratory polygraphy (RP) device with actigraphy (Apnoescreen II; Erich Jaeger GMBH & CoKg; Wuerzburg, Germany) in the diagnosis of sleep apnea-hypopnea syndrome (SAHS). DESIGN: A prospective randomized study with blinded analysis. PATIENTS: Sixty-two patients with suspected SAHS. MEASUREMENTS: the following two RP studies were performed: one in the sleep laboratory (sleep laboratory RP [LRP]), simultaneously with polysomnography; and the other at home (home RP [HRP]). To study the interobserver reliability of RP, two manual analyses were carried out by two different researchers. RESULTS: In LRP, when the respiratory disturbance index was calculated using the total sleep time estimated by actigraphy (RDI) as a denominator, the sensitivity ranged between 94.6% and 100%, and the specificity between 88% and 96.7% for the different cutoff points of the apnea-hypopnea indexes studied. When the respiratory disturbance index was calculated according to the total recording time (RDITRT), the sensitivity was slightly lower (91.6 to 96.9%) and the specificity was similar (92 to 96.7%). In HRP, the sensitivity of the RDI ranged between 83.8% and 95.8%, and the specificity between 92% and 100%, whereas, when the RDITRT was used, the sensitivity was between 83.8% and 87.5%, and the specificity was between 94.7% and 100%. With regard to interobserver reliability, the intraclass correlation coefficient for the RDI of the two analyses of the RP was 0.99 for both LPR and HPR. CONCLUSION: HPR is an effective and reliable technique for the diagnosis of SAHS, although it is less sensitive than LRP. Wrist actigraphy improves the results of HRP only slightly. PMID- 17356087 TI - Association between polysomnographic measures of disrupted sleep and prothrombotic factors. AB - BACKGROUND: Subjective sleep disturbances have been associated with increased risk of coronary artery disease (CAD). We hypothesized that disrupted sleep as verified by polysomnography is associated with increased levels of prothrombotic hemostasis factors previously shown to predict CAD risk. METHODS: Full-night polysomnography was performed in 135 unmedicated men and women (mean age +/- SD, 36.8 +/- 7.8 years) without a history of sleep disorders. Morning fasting plasma levels of von Willebrand Factor (VWF) antigen, soluble tissue factor (sTF) antigen, d-dimer, and plasminogen activator inhibitor (PAI)-1 antigen were determined. Statistical analyses were adjusted for age, gender, ethnicity, body mass index, BP, and smoking history. RESULTS: Higher total arousal index (ArI) was associated with higher levels of VWF (beta = 0.25, p = 0.011, DeltaR(2) = 0.045), and longer wake after sleep onset was associated with higher levels of sTF (beta = 0.23, p = 0.023, DeltaR(2) = 0.038). More nighttime spent at mean oxygen saturation < 90% (beta = 0.20, p = 0.020, DeltaR(2) = 0.029) and higher apnea-hypopnea index (AHI) [beta = 0.19, p = 0.034, DeltaR(2) = 0.024] were associated with higher PAI-1. There was a trend for a relationship between mean oxygen desaturation < 90% and PAI-1 (p = 0.053), even after controlling for AHI. Total ArI (beta = 0.28, p = 0.005, DeltaR(2) = 0.056) and WASO (beta = 0.25, p = 0.017, DeltaR(2) = 0.042) continued to predict VWF and sTF, respectively, even after controlling for AHI. CONCLUSIONS: Polysomnographically verified sleep disruptions were associated with prothrombotic changes. Measures of sleep fragmentation and sleep efficiency were related to VWF and sTF, respectively. Apnea-related measures were related to PAI-1. Our findings suggest that sleep disruptions, even in a relatively healthy population, are associated with potential markers of prothrombotic cardiovascular risk. PMID- 17356088 TI - The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function. AB - BACKGROUND: Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF). METHODS: A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD. RESULTS: The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged. CONCLUSIONS: The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies. PMID- 17356089 TI - Smoothed periodogram of oxyhemoglobin saturation by pulse oximetry in sleep apnea syndrome: an automated analysis. AB - BACKGROUND: Variability of oxyhemoglobin saturation (Spo(2)) during sleep has been utilized as a diagnostic index for sleep apnea. Spectral analysis with its graphical presentation, the periodogram, is an approach for measuring such variability. This work examined the parameters on a smoothed periodogram created from series data for Spo(2) obtained by pulse oximetry during a sleep study. DESIGN AND RESULTS: Spo(2) was recorded during polysomnography study of 273 subjects. Clinical data of subjects were collected retrospectively. A novel automated algorithm was created to measure the low-frequency (< 0.1 Hz) peak and the slope of spectral density vs frequency in the frequency region of 0.1 to 0.5 Hz (slope(0.1-0.5)). Two successive modified Daniell smoothers with span lengths of 3 to 121 in odd numbers were applied to determine the effect of smoothing on these parameters. slope(0.1-0.5) was least affected by smoothing and had a sensitivity of 78% and a specificity of 80% in diagnosing sleep apnea defined by a value of apnea-hypopnea index >/= 5. Combining slope(0.1-0.5) with parameters of the low-frequency peak enlarged the area under the receiver operating characteristic curve. A composite indicator comprised of slope(0.1-0.5) and ratio of the area under the curve of the low-frequency peak to that of whole periodogram (AUCratio) had a positive likelihood ratio of 15.25 in identifying patients with moderate-to-severe obstructive sleep apnea. The algorithm was validated in another 206 patients undergoing polysomnographic studies. CONCLUSIONS: These analytical results demonstrate that the smoothed periodogram of Spo(2) is a useful tool for screening subjects with sleep apnea. PMID- 17356090 TI - Comparison of Dynamic Expiratory CT With Bronchoscopy for Diagnosing Airway Malacia: A Pilot Evaluation. AB - OBJECTIVE: To assess the accuracy of dynamic expiratory CT for detecting airway malacia using bronchoscopy as the diagnostic "gold standard." MATERIALS AND METHODS: A computerized hospital information system was used to retrospectively identify all patients with bronchoscopically proven airway malacia referred for CT airway imaging at our institution during a 19-month period. CT was performed within 1 week of bronchoscopy. All patients were scanned with a standard protocol, including end-inspiratory and dynamic expiratory volumetric imaging, using an eight-detector multislice helical CT scanner. For both CT and bronchoscopy, malacia was defined as >/= 50% expiratory reduction of the airway lumen. CT and bronchoscopic findings were subsequently jointly reviewed by the radiologist and bronchoscopist for concordance. RESULTS: Twenty-nine patients (12 men and 17 women; mean age, 60 years; range, 36 to 79 years) comprised the study cohort. CT correctly diagnosed malacia in 28 of 29 patients (97%). The most common presenting symptoms were dyspnea in 20 patients (69%), severe or persistent cough in 16 patients (55%), and recurrent infection in 7 patients (24%). The estimated radiation dose (expressed as dose-length product) for the dual-phase study is 508 mGy-cm, which is comparable to a routine chest CT. CONCLUSION: Dynamic expiratory CT is a highly sensitive method for detecting airway malacia and has the potential to serve as an effective, noninvasive test for diagnosing this condition. PMID- 17356091 TI - A randomized, placebo-controlled trial of bronchodilators for bronchoscopy in patients with COPD. AB - BACKGROUND: In contrast to asthma, the indication for bronchodilators prior to bronchoscopy in patients with COPD has not been properly investigated. We therefore performed a randomized, double-blind, placebo-controlled trial to determine whether use of a short-acting bronchodilator provides a protective effect in patients with COPD undergoing bronchoscopy. METHODS: One hundred twenty patients undergoing bronchoscopy were included. Patients with COPD were randomized to receive either 200 mug of salbutamol (n = 40) or placebo (n = 40) before bronchoscopy. Control patients (n = 40) did not receive any inhaled medication. Spirometry was performed before and 2 h after bronchoscopy in all patients. Sedative drug requirements and hemodynamic parameters were recorded. RESULTS: Hemodynamic findings before, during, and after bronchoscopy were similar in patients with COPD randomized to either salbutamol or placebo (p = not significant for all). Compared to prebronchoscopy values, postbronchoscopy percentage of predicted FEV(1) decreased significantly in all three groups: salbutamol (median, - 4.7%; interquartile range [IQR], - 13.3 to 6.6); placebo (median, - 4.8%; IQR, - 19.9 to 8.4); and control subjects (median, - 10.0%; IQR, - 20.2 to - 3.3) [p = 0.023]. The decrease in FEV(1) was similar in all three patient groups (p = 0.432). The relative change in FEV(1) was inversely correlated to the increasing severity of COPD as expressed by Global Initiative for Chronic Obstructive Lung Disease stages (p = 0.01). CONCLUSIONS: Premedication with an inhaled short-acting beta-agonist cannot be recommended in patients with COPD undergoing bronchoscopy. PMID- 17356092 TI - Conventional transbronchial needle aspiration decreases the rate of surgical sampling of intrathoracic lymphadenopathy. AB - BACKGROUND: Previous studies have suggested a decreased need for the surgical biopsy of intrathoracic lymph nodes (LNs) due to improved diagnostic rates utilizing transbronchial needle aspiration (TBNA) with endobronchial ultrasound and endoscopic ultrasound. The goal of this study was to determine whether conventional TBNA using combined cytologic and histologic analysis of tissue specimens impacted the rates of surgical diagnostic biopsies of patients with intrathoracic lymphadenopathy. METHODS: Retrospective review at a single academic center. All mediastinal and hilar tissue samples submitted for pathologic analysis over an 8.4-year period were analyzed. Patients were categorized into a "before" group and an "after" group based on two different time periods. The before group underwent only cytologic analysis of Wang needle (19-gauge or 21 gauge) aspirates. The after group had cytologic analysis of aspirates as well as histologic analysis of needle "core" (19 gauge) biopsy specimens. The groups were compared for the rate of intrathoracic LNs sampled by surgical means vs TBNA and the number of times that TBNA averted the need for a surgical diagnostic procedure. RESULTS: The success of TBNA increased significantly in the after group compared to that in the before group. The yield for the successful sampling of mediastinal and hilar LNs increased from 53 to 91% (p < 0.001) in the before group vs the after group. TBNA averted a surgical biopsy in 35% of the before cases compared to 66% of the after cases (p < 0.001). CONCLUSIONS: Conventional TBNA using large-bore needles with both cytology and surgical pathology evaluation decreases the need for surgical sampling of the mediastinum to diagnose thoracic lymphadenopathy. PMID- 17356093 TI - Etiology of community-acquired pneumonia in hospitalized patients in chile: the increasing prevalence of respiratory viruses among classic pathogens. AB - BACKGROUND AND STUDY OBJECTIVES: The range and relative impact of microbial pathogens, particularly viral pathogens, as a cause of community-acquired pneumonia (CAP) in hospitalized adults has not received much attention. The aim of this study was to determine the microbial etiology of CAP in adults and to identify the risk factors for various specific pathogens. METHODS: We prospectively studied 176 patients (mean [+/- SD] age, 65.8 +/- 18.5 years) who had hospitalized for CAP to identify the microbial etiology. For each patient, sputum and blood cultures were obtained as well as serology testing for Mycoplasma pneumoniae and Chlamydophila pneumoniae, urinary antigen testing for Legionella pneumophila and Streptococcus pneumoniae, and a nasopharyngeal swab for seven respiratory viruses. RESULTS: Microbial etiology was determined in 98 patients (55%). S pneumoniae (49 of 98 patients; 50%) and respiratory viruses (32%) were the most frequently isolated pathogen groups. Pneumococcal pneumonia was associated with tobacco smoking of > 10 pack-years (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2 to 5.4; p = 0.01). Respiratory viruses were isolated more often in fall or winter (28%; p = 0.011), and as an exclusive etiology tended to be isolated in patients >/= 65 years of age (20%; p = 0.07). Viral CAP was associated with antimicrobial therapy prior to hospital admission (OR, 4.5; 95% CI, 1.4 to 14.6). CONCLUSIONS: S pneumoniae remains the most frequent pathogen in adults with CAP and should be covered with empirical antimicrobial treatment. Viruses were the second most common etiologic agent and should be tested for, especially in fall or winter, both in young and elderly patients who are hospitalized with CAP. PMID- 17356094 TI - Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis. AB - BACKGROUND: Treatment of hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis is mainly supportive. Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. Because hypoxia and airways obstruction develop secondary to viscous mucus in infants with RSV bronchiolitis, and because free DNA is present in RSV mucus, we tested the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase). METHODS: In a multicenter, randomized, double-blind, controlled clinical trial, 225 oxygen-dependent infants admitted to the hospital for RSV bronchiolitis were randomly assigned to receive 2.5 mg bid of nebulized rhDNase or placebo until discharge. The primary end point was length of hospital stay. Secondary end points were duration of supplemental oxygen, improvement in symptom score, and number of intensive care admissions. RESULTS: There were no significant differences between the groups with regard to the length of hospital stay (p = 0.19) or the duration of supplemental oxygen (p = 0.07). The ratio (rhDNase/placebo) of geometric means of length of stay was 1.12 (95% confidence interval, 0.96 to 1.33); for the duration of supplemental oxygen, the ratio was 1.28 (95% confidence interval, 0.97 to 1.68). There were no significant differences in the rate of improvement of the symptom score or in the number of intensive care admissions. CONCLUSIONS: Administration of rhDNase did not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen dependent infants with RSV bronchiolitis. PMID- 17356095 TI - Levofloxacin pharmacokinetics in adult cystic fibrosis. AB - BACKGROUND: Cystic fibrosis (CF) patients have enhanced renal clearance of aminoglycosides and several beta-lactams and require higher dosages. Levofloxacin is a fluoroquinolone with extensive renal elimination and enhanced penetration into lungs and Pseudomonas aeruginosa (PA) biofilms. We studied the preliminary pharmacokinetic and pharmacodynamic (PK/PD) relationship of levofloxacin in CF. METHODS: Twelve patients at least 18 years old with a mild-to-moderate pulmonary exacerbation and fluoroquinolone-sensitive PA colonization received oral levofloxacin, 500 mg qd, for 14 days. Steady-state serum concentrations were collected after 3 to 7 days, and sputum samples for PA densities were collected before and after levofloxacin. PK/PD relationships for reducing PA sputum densities were evaluated. RESULTS: When compared to published data on non-CF patients, CF patients had similar area under the curve for 24 h (AUC(24)), total clearance, volume of distribution, maximum serum concentration (Cpmax), and elimination half-life: mean, 7.33 microg x h/mL/kg (SD, 1.70); 2.43 mL/min/kg (SD, 0.74); 1.33 L/kg (SD, 0.37); 7.06 microg/mL (SD, 2.35); and 6.44 h (SD, 1.1), respectively. Time to reach maximum serum concentration (Tmax) in CF was longer: mean, 2.20 h (SD, 0.99) vs 1.1 h (SD, 0.4) [p < 0.01]. Preliminary PK/PD analysis failed to demonstrate trends for decreasing PA sputum densities with increasing Cpmax/minimum inhibitory concentration (MIC) ratio and AUC(24)/MIC ratio. CONCLUSION: CF levofloxacin pharmacokinetics corrected for body weight are similar to non-CF, except for Tmax. Standard levofloxacin dosing (especially monotherapy) is unlikely to produce maximum therapeutic effectiveness. Additional levofloxacin studies in CF are necessary to evaluate its sputum concentrations; the benefits of higher daily dosages (>/= 750 mg); and establish PK/PD targets for managing PA pulmonary infections. PMID- 17356096 TI - Hepatitis C virus infection and hepatotoxicity during antituberculosis chemotherapy. AB - BACKGROUND: The risk of drug-induced hepatotoxicity (DIH) during treatment for tuberculosis (TB) in patients who are seropositive for the hepatitis C virus (HCV) is not clear. We evaluated whether HCV-seropositive patients are at a higher risk of DIH than control subjects during treatment for TB with standard short-course regimens. METHODS: Fifty-four HCV-seropositive patients with newly diagnosed active TB who were treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Ninety-seven HCV-seronegative patients were selected as control subjects. RESULTS: Forty HCV-seropositive patients (74%) and 82 control subjects (85%) received an initial treatment regimen that included pyrazinamide. Twenty-two HCV-seropositive patients (41%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during TB treatment, including transient elevation of transaminase. DIH, defined as a liver transaminase level >/= 120 IU/L, occurred more frequently in HCV-seropositive patients (7 of 54 patients, 13%) than in control subjects (4 of 97 patients, 4%). Isoniazid and rifampin were reintroduced after the liver transaminase level returned to baseline in five HCV-seropositive patients exhibiting DIH, and all these retrials proved to be successful. CONCLUSIONS: These findings suggest that treatment for TB in HCV-seropositive patients could be pursued in the usual manner, using standard short-course regimens, with the condition that monthly liver function tests are carefully performed. PMID- 17356097 TI - Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy. AB - BACKGROUND: Platelet microparticles (PMPs), are procoagulant membrane vesicles that are derived from activated platelets, the levels of which are elevated in patients with hypertension, coronary artery disease (CAD), diabetes, and stroke, all of which are conditions that lead to (and are associated with) atrial fibrillation (AF). We hypothesized the following: (1) PMP levels are elevated in patients with AF compared to levels in both healthy control subjects (ie, patients without cardiovascular diseases who are in sinus rhythm) and disease control subjects (ie, patients with hypertension, CAD, diabetes or stroke, but who are in sinus rhythm); (2) PMP levels correlate with levels of soluble P selectin (sP-selectin) [a marker of platelet activation]; and (3) PMP levels are related to the underlying factors in patients with AF that contribute to the overall risk of stroke secondary to AF. METHODS: We performed a case-control study of 70 AF patients, 46 disease control subjects and 33 healthy control subjects. Peripheral venous levels of PMP and sP-selectin were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Both AF patients and disease control subjects had significantly higher levels of PMPs (p < 0.001) and sP-selectin (p = 0.001) compared to healthy control subjects, but there was no difference between AF patients and disease control subjects. There was no difference in PMP levels between patients with paroxysmal and permanent AF (p = 0.581), and between those receiving therapy with aspirin and warfarin (p = 0.779). No significant correlation was observed between PMP and sP-selectin levels (p = 0.463), and the clinical characteristics that contribute to increased stroke risk in patients with AF. On stepwise multiple regression analysis in the combined cohort of AF patients plus disease control subjects, the presence/absence of AF was not an independent determinant of PMP and sP-selectin levels. CONCLUSION: There is evidence of platelet activation (ie, high PMP and sP selectin levels) in AF patients, but this is likely to be due to underlying cardiovascular diseases rather than the arrhythmia per se. PMID- 17356098 TI - Falsely elevated international normalized ratio values in patients undergoing anticoagulation therapy: a descriptive evaluation. AB - BACKGROUND: Elevated international normalized ratio (INR) values have been linked to bleeding complications; however, elevated INR values are not always physiologic and can be falsely increased. This study describes the rate of falsely elevated INRs and characteristics predictive of falsely elevated INRs. METHODS: This cross-sectional study was conducted among adult patients receiving anticoagulation therapy monitored by a centralized anticoagulation service during January 2000 through December 2004 (n = 29,536). Prevalence rates of all elevated (ie, value >/= 10), falsely elevated, and truly elevated INRs were calculated. Multivariate logistic regression was performed to identify predictors of falsely elevated INRs among elevated INRs. RESULTS: Of the 556,998 INRs included in the analysis, 793 INRs (prevalence, 0.14%; 95% confidence interval [CI], 0.10 to 0.19%), 53 INRs (prevalence, 0.01%; 95% CI, < 0.01 to 0.03%), and 740 INRs (prevalence, 0.13%; 95% CI, 0.09 to 0.18%) were elevated, falsely elevated, and truly elevated, respectively. The strongest independent predictor of a falsely elevated INR was a patient undergoing hemodialysis at the time of the elevated INR (adjusted odds ratio, 9.60; 95% CI, 4.96 to 18.58; p < 0.001). A low target INR was the only other factor found to be an independent predictor of a falsely elevated INR. CONCLUSIONS: Although INR values >/= 10.0 occur infrequently, patients presenting with such values can present a challenge to the anticoagulation provider. Anticoagulation providers should be particularly vigilant for falsely elevated INRs when monitoring patients undergoing hemodialysis. PMID- 17356099 TI - Updated evaluation of the cost-effectiveness of lung volume reduction surgery. AB - BACKGROUND: The National Emphysema Treatment Trial, a randomized clinical trial of lung volume reduction surgery (LVRS) vs medical therapy for severe emphysema, included a prospective economic analysis. We present an updated analysis of cost effectiveness with 1-year additional follow-up data. METHODS: Following pulmonary rehabilitation, 1,218 patients at 17 medical centers were randomized to receive LVRS or continued medical treatment. The cost-effectiveness of LVRS vs medical therapy was calculated over the duration of the trial (January 1998 to December 2003) and estimated at 10 years using modeling based on observed trends in survival, cost, and quality of life. RESULTS: The cost-effectiveness of LVRS vs medical therapy was $140,000 per quality-adjusted life-year (QALY) gained (95% confidence interval, $40,155 to $239,359) at 5 years, and was projected to be $54,000 per QALY gained at 10 years. In subgroup analysis, the cost-effectiveness of LVRS in patients with upper-lobe emphysema and low exercise capacity was $77,000 per QALY gained at 5 years, and was projected to be $48,000 per QALY at 10 years. Compared to the initial results, the updated results are similar for the overall cohort but vary substantially for the subgroups. CONCLUSIONS: LVRS is costly relative to other health-care programs during the time horizon when costs and outcomes are known. The extended follow-up period offers more certainty regarding the long-term value and economic impact of this procedure. PMID- 17356100 TI - The impact of new-onset atrial fibrillation on in-hospital mortality following cardiac surgery. AB - BACKGROUND: The impact of new-onset postoperative atrial fibrillation (NAF) on in hospital mortality (IHM) following cardiac surgery is unknown. METHODS: All patients without preoperative atrial fibrillation undergoing isolated coronary artery bypass graft surgery (CABG) and concomitant CABG and valve surgery were identified (n = 7,347). The association between NAF and IHM was determined using logistic regression modeling. Also, propensity score analysis was used to create two matched subgroups of patients with and without NAF (n = 2,015 in each group). The secondary outcomes examined were stroke, myocardial infarction (MI), intra aortic balloon pump use, GI complications, deep sternal wound infection (DSWI), septicemia, renal failure, and length of stay. RESULTS: NAF developed in 2,047 patients (27.9%). NAF was not an independent predictor of IHM (odds ratio, 0.8; 95% confidence interval, 0.6 to 1.2; p = 0.3). In multivariate analysis, NAF was associated with age >/= 60 years, combined procedures, preoperative MI within 7 days of surgery, COPD, cerebrovascular disease, and male gender. Propensity adjusted results revealed no difference in IHM between NAF vs no-NAF patients (2.9% vs 3.5%, respectively; Bonferroni-corrected p = 0.99). However, GI complications (4.2% vs 2.1%), DSWI (1.3% vs 0.4%), septicemia (4.0% vs 1.1%), renal failure (7.6% vs 4.3%), and length of stay (8 days vs 6 days) were significantly increased in patients with NAF. CONCLUSION: NAF following cardiac surgery is not associated with increased IHM. PMID- 17356101 TI - Prognosis of lung cancer patients with life-threatening complications. AB - BACKGROUND: The management of patients with lung cancer has improved recently, and many of them will require admission to the ICU. The aims of this study were to determine hospital mortality and to identify risk factors for death in a large cohort of critically ill patients. METHODS: Cohort study in two ICUs specialized in the management of patients with cancer, in France and Brazil. RESULTS: Of the 143 patients (mean age, 61.6 +/- 9.9 years [+/- SD]), 25 patients (17%) had small cell lung cancer and 118 patients (83%) had non-small cell lung cancer. The main reasons for ICU admission were sepsis (44%) and acute respiratory failure (31%). Mechanical ventilation (MV) was used in 100 patients (70%), including 38 patients in whom lung cancer was considered a reason for MV. Hospital mortality was 59% overall and 69% in patients receiving MV. By multivariate logistic regression, airway infiltration or obstruction by cancer, number of organ failures, cancer recurrence or progression, and severity of comorbidities were associated with increased mortality. CONCLUSIONS: The improved survival previously reported in patients with cancer admitted to the ICU seems to extend to patients with lung cancer, including those who need MV. Mortality increased with the number of organ failures, severity of comorbidities, and presence of respiratory failure due to cancer progression. The type of the cancer per se was not associated with mortality and, therefore, should not be factored into ICU triage decisions. PMID- 17356102 TI - Microscopic-sized "microthymoma" in patients with myasthenia gravis. AB - BACKGROUND: In 2005, Cheuk et al reported two patients with microscopic-sized thymomas and proposed the term microthymoma to distinguish it from the nodular hyperplasia of thymic epithelium, so-called microscopic thymoma. Here, we present microthymomas that were found in 196 patients with myasthenia gravis (MG) who had undergone thymectomy. MATERIALS AND METHODS: Thymic tissues in 196 patients with MG who underwent thymectomy or thymothymomectomy were examined. Of these patients, 73 patients had thymoma indicated by CT before surgery, and the other 123 patients had no mediastinal tumors. From the resected thymic tissues, an average of 14 hematoxylin-eosin-stained sections (range, 4 to 55 sections) were prepared for microscopic examination. The histologic type of the thymoma was classified according to the World Health Organization (WHO) classification. RESULTS: From the 196 patients, we found three microthymomas in 3 patients (1.5%). While these three tumors could not be seen grossly in pathology section, they were found microscopically (range, 2 to 4 mm). The histologic subtype according to the WHO classification system was B1 in one patient and B2 in two patients. CONCLUSION: Microthymoma was found in 3 of 196 patients (1.5%) with MG. Microthymoma might exist in thymus of patients with MG, even in patients who have no thymoma indicated by CT. PMID- 17356103 TI - Platelet-derived growth factor is increased in pulmonary capillary hemangiomatosis. AB - BACKGROUND: Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary arterial hypertension with no effective medical therapy and a high risk of mortality. The pathogenesis of PCH is unknown. METHODS: We used gene expression analysis to compare lung tissue samples from two patients with PCH to those from seven control subjects. The nodules of proliferating capillaries in PCH patients were needle microdissected from cryostat sections. RNA extraction and labeling were followed by hybridization to U95Av2 oligonucleotide arrays (Affymetrix; Santa Clara, CA). In situ hybridization and immunohistochemistry were also performed. RESULTS: The gene expression profile of PCH allowed for unsupervised clustering from the profile of the lung tissue samples of control subjects. Platelet-derived growth factor (PDGF)-B gene (PDGFB), PDGF receptor (PDGFR)-beta gene (PDGFR-beta), mast cell-related genes, and type 2 pneumocyte related genes were found to be overexpressed in PCH lesions. In situ hybridization as well as immunohistochemistry for PDGFB showed expression by type 2 pneumocytes and endothelial cells. Immunohistochemical staining for PDGFR-beta localized to pericytic/vascular smooth muscle cells surrounding the proliferating capillaries. CD117 staining confirmed an abundance of mast cells in the lesions, which also stained heavily for PDGFR-beta. CONCLUSIONS: The expression of the PDGFB and PDGFR-beta genes characterizes the nodular proliferations of PCH. Increased numbers of mast cells, pericytes, and type II pneumocytes accompany the endothelial proliferation. The up-regulation of these important angiogenic and antiapoptotic genes suggests a mechanism and potential therapeutic approaches for PCH. PMID- 17356105 TI - Change in prevalence of asbestos-related disease among sheet metal workers 1986 to 2004. AB - In 1985, the Sheet Metal Workers International Association and the Sheet Metal and Air Conditioning National Association formed The Sheet Metal Occupational Health Institute Trust to examine the health hazards of the sheet metal industry in the United States and Canada. Between 1986 and 2004, 18,211 individuals were examined. The mean age of this cohort was 57.9 years, and the participants had worked for a mean (+/- SD) duration of 32.9 +/- 6 years in the sheet metal trade. Twenty-three percent of participants were current smokers, 49% were former smokers, and 28% were never-smokers. A total of 9.6% of participants (1,745 participants) had findings that were consistent with parenchymal disease (International Labor Organization [ILO] score, >/= 1/0); 60% of those with an ILO score >/= 1/0 were classified as 1/0, 34% as 1/1 to 1/2, and 6% as >/= 2/1. A total of 21% of participants (3,827 participants) had pleural scarring. There was a lower prevalence of nonmalignant asbestos-related disease among those who began to work after 1970, when compared to workers who began to work before 1949; those who began to work between 1950 and 1969 had a prevalence between the other two groups. The strongest predictor of both parenchymal and pleural disease on a chest radiograph was the calendar year in which the worker began sheet metal work; work in a shipyard was also an important risk. The results of this study suggest that the efforts to reduce asbestos exposure in the 1980s through strengthened Occupational Safety and Health Administration regulation have had a positive public health impact. PMID- 17356104 TI - The role of air nicotine in explaining racial differences in cotinine among tobacco-exposed children. AB - OBJECTIVE: African-American children have higher rates of tobacco-associated morbidity. Few studies have objectively measured racial differences in the exposure of children to tobacco smoke. The objective of this study was to test whether African-American children have higher levels of cotinine compared to white children while accounting for ambient measures of tobacco smoke. SETTING: Community-based sample of asthmatic children (n = 220) enrolled in an environmental tobacco smoke (ETS) reduction trial. PARTICIPANTS: A biracial sample (55% African American) of children with asthma aged 5 to 12 years who were routinely exposed to ETS. MEASUREMENTS: We measured cotinine levels in serum and hair samples at baseline, 6 months, and 12 months. We measured the level of ETS exposure over a 6-month period by placing air nicotine dosimeters in the homes of the children at baseline and at 6-month study visits. RESULTS: African-American children had significantly higher levels of cotinine at all time points in the study. At the 12-month visit, African-American children had higher levels of serum cotinine (1.39 mug/dL vs 0.80 mug/dL, p = 0.001) and hair cotinine (0.28 ng/mg vs 0.08 ng/mg, p < 0.0001) when compared with white children. In a repeated measures analysis, African-American children had significantly higher levels of serum cotinine (beta = 0.28, p = 0.04) and hair cotinine (beta = 1.40, p < 0.0001) compared with white children. Air nicotine levels and housing volume were independently associated with higher levels of cotinine. CONCLUSIONS: Among children with asthma, African-American children have higher levels of serum and hair cotinine compared with white children. PMID- 17356106 TI - Nasal nitric oxide in atypical primary ciliary dyskinesia. AB - BACKGROUND: Atypical cases of primary ciliary dyskinesia (PCD) may present with minimal transmission electron microscopy (TEM) defects. The diagnostic role of nasal nitric oxide (nNO) levels was evaluated in those patients. METHODS: Sixty four children with recurrent pneumonia were studied with ciliary motion analysis, TEM, and nNO. RESULTS: Investigations indicated PCD in 12 patients, secondary ciliary dyskinesia (SCD) in 50 patients, and normal results in 2 patients. In 4 of 50 children with SCD, atypical PCD was considered possible. The mean (+/- SD) nNO was 130 +/- 46.95 parts per billion in children affected by PCD, 127.79 +/- 68.58 parts per billion in atypical patients, and 760 +/- 221 parts per billion in children with SCD. Three to 5 months later, the nNO level was 132.75 +/- 55.76 parts per billion in children with atypical disease and 778.00 +/- 197 parts per billion in children with SCD. CONCLUSION: Low levels of nNO may help to identify patients with atypical PCD. PMID- 17356108 TI - Diagnosis and treatment of tuberculous pleural effusion in 2006. AB - Tuberculous (TB) pleural effusion occurs in approximately 5% of patients with Mycobacterium tuberculosis infection. The HIV pandemic has been associated with a doubling of the incidence of extrapulmonary TB, which has resulted in increased recognition of TB pleural effusions even in developed nations. Recent studies have provided insights into the immunopathogenesis of pleural TB, including memory T-cell homing and chemokine activation. The definitive diagnosis of TB pleural effusions depends on the demonstration of acid-fast bacilli in the sputum, pleural fluid, or pleural biopsy specimens. The diagnosis can be established in a majority of patients from the clinical features, pleural fluid examination, including cytology, biochemistry, and bacteriology, and pleural biopsy. Measurement of adenosine deaminase and interferon-gamma in the pleural fluid and polymerase chain reaction for M tuberculosis has gained wide acceptance in the diagnosis of TB pleural effusions. Although promising, these tests require further evaluation before their routine use can be recommended. The treatment of TB pleural effusions in patients with HIV/AIDS is essentially similar to that in HIV-negative patients. At present, evidence regarding the use of corticosteroids in the treatment of TB pleural effusion is not clear-cut. PMID- 17356109 TI - Journal reporting of medical errors: the wisdom of Solomon, the bravery of Achilles, and the foolishness of Pan. AB - Medical errors may result from lapses in judgment or lack of prudent care by individual physicians, from system errors inherent in the medical-care delivery model or, more frequently, from a combination of the two. Medical error reporting is a sensitive topic for physicians, institutions, and patients. The veil of secrecy that surrounds medical errors deprives health-care practitioners of knowledge that may help prevent similar adverse outcomes for patients in the future. Although reporting individual medical errors to involved patients is obligatory by most professional codes of conduct for physicians, no laws or professional society guidelines mandate widespread reporting of errors to professional colleagues. Furthermore, reports of medical errors in peer-reviewed journals are extremely rare. In 2000, the Joint Commission for Accreditation of Healthcare Organizations described systemic medical errors as "fundamentally an information problem" and called for the development of programs to collect and analyze medical error data. In this review, we define medical errors and detail common motivations and barriers to publication of error reports. We propose a model for confidential error communication and describe US legislation designed to improve patient safety and establish nationwide programs for error disclosure and analysis. PMID- 17356107 TI - Angiogenesis in chronic lung disease. AB - Chronic lung diseases like COPD, severe progressive pulmonary hypertension (PH), and interstitial lung diseases all have a lung vascular disease component. Cellular and molecular mechanisms of pulmonary vascular remodeling have been experimentally explored in many animal models, and it is now clear that microvessels are involved. In emphysema patients, there is a loss of lung microvessels, and in many forms of severe PH there is obliteration of precapillary arterioles by angioproliferation. Thus, COPD/emphysema and severe angioproliferative PH are on the opposite ends of a spectrum of vascular biology responses. Animal experiments have provided insight regarding some of the initiating events that shape the various forms of pulmonary vascular remodeling. In pulmonary fibrosis and in the postinjury phase of acute lung injury, the angiogenic/angiostatic balance is also affected. This review will therefore discuss angiogenesis in several chronic lung diseases and will speculate on how altered vascular homeostasis may contribute to lung disease development. PMID- 17356110 TI - Sildenafil improves walk distance in idiopathic pulmonary fibrosis. AB - Pulmonary hypertension is a common finding in patients with idiopathic pulmonary fibrosis (IPF), and is associated with increased morbidity and mortality. Therapy with sildenafil has been shown to decrease pulmonary vascular resistance in patients with pulmonary fibrosis and may improve functional status. Patients with IPF and documented pulmonary hypertension were followed up in an open-label study of sildenafil. The 6-min walk test distance (6MWD) was obtained before and after 3 months of sildenafil therapy. Fourteen patients were followed up in the study; 11 patients completed both 6-min walk tests. The mean improvement in walk distance was 49.0 m (90% confidence interval, 17.5 to 84.0 m). When all 14 patients were dichotomized into groups of "responders" (ie, >/= 20% improvement in 6MWD) or "nonresponders" (ie, < 20% change or unable to complete), 57% were classified as responders. Sildenafil is a promising and well-tolerated therapeutic agent for use in patients with IPF and pulmonary hypertension, and should be studied in a large, well-controlled trial. PMID- 17356111 TI - Video-assisted thorascopic removal of migratory acupuncture needle causing pneumothorax. AB - We report the case of a 25-year-old African-American man presenting to the Henry Ford Hospital emergency department with acute dyspnea secondary to a pneumothorax resulting from a migratory acupuncture needle. The patient received acupuncture treatment approximately 5 years prior to this presentation for treatment of posttraumatic chronic right shoulder pain. Chest radiography revealed retained needles in his right shoulder girdle and a needle overlying the thoracic cage with an attendant pneumothorax. Catheter aspiration for simple pneumothorax provided immediate symptomatic relief. Video-assisted thoracoscopy was then used to remove the migratory acupuncture needle from the chest wall. The patient recovered without complication and was discharged to home. PMID- 17356112 TI - Eosinophilic pneumonia due to duloxetine. AB - A 32-year-old man presented with a 2-month history of worsening fever, chills, and cough despite therapy with oral antibiotics. Chest radiographs demonstrated migrating, peripheral upper lobe infiltrates. A CBC count demonstrated significant eosinophilia. At bronchoscopy, eosinophil-rich mucus was seen impacted throughout his bronchi. A transbronchial biopsy confirmed the diagnosis of eosinophilic pneumonia. Symptoms, eosinophilia, and radiographic abnormalities were reversed with cessation of duloxetine. This case report briefly reviews the diagnosis of drug-induced pulmonary infiltrates with eosinophilia (PIEs) and eosinophilic pneumonia. To our knowledge, this is the first reported case of PIEs due to duloxetine. PMID- 17356113 TI - Dyspnea with slow-growing mass of the left hemithorax. AB - We report a case of a 65-year-old male patient who presented with gradually worsening dyspnea over 2 years. History was significant for smoking and the absence of any hazardous occupational exposure. The clinical findings at presentation included absent breath sounds and stony dullness on the left side, with tracheal deviation contralaterally and clubbing. A chest roentgenogram showed a left-sided opacity occupying almost the entire left hemithorax. A subsequent CT scan of the chest revealed an intrathoracic, extrapulmonary lesion producing a mediastinal shift. Surgical resection of the mass was performed, and pathology, along with immunohistochemical studies positive for CD34 and negative for epithelial markers, confirmed the diagnosis of solitary fibrous tumor of the pleura (SFTP). SFTP is a rare neoplasm, and diagnosis is often difficult. Suspicion of SFTP should arise in the setting of a patient presenting with a paucity of symptoms (except in the case of an accompanying paraneoplastic syndrome), the absence of exposure to asbestos, and a large mass with sharp margins and encapsulation seen on a chest radiograph. PMID- 17356114 TI - Nonventilatory treatments for acute lung injury and ARDS. AB - Over the past decade, advances in the ventilatory management of acute lung injury (ALI) and ARDS have improved outcomes; however, until recently the search for other therapies has been less fruitful. Recently, the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial reported that a conservative fluid management strategy, compared with a fluid liberal strategy, increased the mean (+/- SE) number of ventilator-free days in patients with ALI (14.6 +/- 0.5 vs 12.1 +/- 0.5 days, respectively; p < 0.001). In addition to this beneficial effect on outcomes, the study found that the conservative fluid strategy did not increase the incidence of renal failure or the development of shock. Other studies have demonstrated that albumin and furosemide therapy may be beneficial in hypoproteinemic patients with lung injury, though data on outcomes is still lacking. Although several pharmacologic therapies, such as corticosteroids, surfactant, and nitric oxide, have been demonstrated to be ineffective in improving outcomes, several promising new treatments are being investigated in ongoing or upcoming clinical trials. This article reviews these developments and other recent research on the optimal nonventilatory management of patients with ALI. PMID- 17356115 TI - Mechanical ventilation in ARDS: a state-of-the-art review. AB - Mechanical ventilation is an essential component of the care of patients with ARDS, and a large number of randomized controlled clinical trials have now been conducted evaluating the efficacy and safety of various methods of mechanical ventilation for the treatment of ARDS. Low tidal volume ventilation (or= ATPgammaS > CTP, a similar agonist potency profile to that of cloned P2X(4) receptors but with higher sensitivity for beta, gamma-methylene-ATP and alpha,beta-methylene-ATP. We further demonstrated that the ATP effect on sodium transport was potentiated by ivermectin, not blocked by suramin and PPADS, enhanced by Zn(2+) but not by Cu(2+), and significantly reduced but not totally inhibited by brilliant blue G. These results led us to conclude that basolateral P2X(4)-like receptors were involved. We suggest that there is a reciprocal purinergic system acting both at a basolateral and apical location for control of Na(+) transport. This requires a mechanism within the cell that leads to either basolateral or apical ATP release to regulate renal tubular function. PMID- 17356128 TI - Endogenous urokinase lacks antifibrotic activity during progressive renal injury. AB - Interstitial fibrosis is a universal feature of progressive kidney disease. Urokinase-type plasminogen activator (uPA) is thought to participate for several reasons: 1) uPA is produced predominantly in kidney, 2) its inhibitor plasminogen activator inhibitor-1 (PAI-1) is a strong promoter of interstitial fibrosis, whereas its receptor (uPAR) attenuates renal fibrosis, 3) uPA reduces fibrosis in liver and lung, and 4) uPA can activate hepatocyte growth factor (HGF), a potent antifibrotic growth factor. The present study tested the hypothesis that endogenous uPA reduces fibrosis severity by investigating the unilateral ureteral obstruction (UUO) model in wild-type (WT) and uPA-/- mice. Several outcomes were measured: renal collagen 3-21 days after UUO, macrophage accumulation (F4/80 Western blotting), interstitial myofibroblast density (alpha-smooth muscle actin immunostaining), and tubular injury (E-cadherin and Ksp-cadherin Western blotting). None of these measures differed significantly between WT and uPA-/- mice. uPA genetic deficiency was not associated with compensatory changes in renal uPAR mRNA levels, PAI-1 protein levels, or tissue plasminogen activator activity levels after UUO. Despite the known ability of uPA to activate latent HGF, immunoblotting failed to detect significant differences in levels of the active HGF alpha-chain and phosphorylated cMET (the activated HGF receptor) between the WT and uPA-/- groups. These findings suggest that the profibrotic actions of PAI-1 are uPA independent and that an alternative pathway must activate HGF in kidney. Finally, these results highlight a significant organ specific difference in basic fibrogenic pathways, as enhanced uPA activity has been reported to attenuate pulmonary and hepatic fibrosis. PMID- 17356129 TI - S1P modulator FTY720 limits matrix expansion in acute anti-thy1 mesangioproliferative glomerulonephritis. AB - FTY720 is a novel immune modulator whose primary action is blood lymphocyte depletion through interaction with sphingosine-1-phosphate (S1P) receptors. The present study analyzes the effect of FTY720 on both the early mesangial cell injury and the subsequent matrix expansion phase of experimental mesangioproliferative glomerulonephritis. Disease was induced by injection of OX 7 anti-thy1 antibody into male Wistar rats. In both protocols, FTY720 administration (0.3 mg/kg body wt) resulted in a selective and very marked reduction in blood lymphocyte count. In the injury experiment, the S1P receptor modulator was given starting 5 days before and continued until 1 day after antibody injection. FTY720 did not significantly affect the degree of anti-thy1 induced mesangial cell lysis and glomerular-inducible nitric oxide production. In the matrix expansion experiment, FTY720 treatment was started 1 day after antibody injection and continued until day 7. In this protocol, the S1P modulator reduced proteinuria, histological matrix expansion, and glomerular protein expression of TGF-beta(1), fibronectin, and PAI-1. Glomerular collagen III staining intensity was decreased. FTY720 reduced markedly glomerular lymphocyte number per cross section and to a lesser degree macrophage infiltration. In conclusion, FTY720 significantly limits TGF-beta(1) overexpression and matrix protein expression following induction of acute anti-thy glomerulonephritis, involving reductions in blood and glomerular lymphocyte numbers. The results suggest that lymphocytes actively contribute to matrix expansion in experimental mesangioproliferative glomerulonephritis. Our study expands on findings on FTY720's beneficial effects on tubulointerstitial and functional disease progression previously reported in anti-thy1-induced chronic glomerulosclerosis. PMID- 17356130 TI - NH2 terminus of serum and glucocorticoid-regulated kinase 1 binds to phosphoinositides and is essential for isoform-specific physiological functions. AB - Serum and glucocorticoid regulated kinase 1 (SGK1) has been identified as a key regulatory protein that controls a diverse set of cellular processes including sodium (Na(+)) homeostasis, osmoregulation, cell survival, and cell proliferation. Two other SGK isoforms, SGK2 and SGK3, have been identified, which differ most markedly from SGK1 in their NH(2)-terminal domains. We found that SGK1 and SGK3 are potent stimulators of epithelial Na(+) channel (ENaC)-dependent Na(+) transport, while SGK2, which has a short NH(2) terminus, is a weak stimulator of ENaC. Further characterization of the role of the SGK1 NH(2) terminus revealed that its deletion does not affect in vitro kinase activity but profoundly limits the ability of SGK1 either to stimulate ENaC-dependent Na(+) transport or inhibit Forkhead-dependent gene transcription. The NH(2) terminus of SGK1, which shares sequence homology with the phosphoinositide 3-phosphate [PI(3)P] binding domain of SGK3, binds phosphoinositides in protein lipid overlay assays, interacting specifically with PI(3)P, PI(4)P, and PI(5)P, but not with PI(3,4,5)P(3). Moreover, a point mutation that reduces phosphoinositide binding to the NH(2) terminus also reduces SGK1 effects on Na(+) transport and Forkhead activity. These data suggest that the NH(2) terminus, although not required for PI 3-kinase-dependent modulation of SGK1 catalytic activity, is required for multiple SGK1 functions, including stimulation of ENaC and inhibition of the proapoptotic Forkhead transcription factor. Together, these observations support the idea that the NH(2)-terminal domain acts downstream of PI 3-kinase-dependent activation to target the kinase to specific cellular compartments and/or substrates, possibly through its interactions with a subset of phosphoinositides. PMID- 17356131 TI - Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine zipper. AB - Dendritic cells (DCs) determine whether antigen presentation leads to immune activation or to tolerance. Tolerance-inducing DCs (also called regulatory DCs) act partly by generating regulatory T lymphocytes (Tregs). The mechanism used by DCs to switch toward regulatory DCs during their differentiation is unclear. We show here that human DCs treated in vitro with glucocorticoids produce the glucocorticoid-induced leucine zipper (GILZ). Antigen presentation by GILZ expressing DCs generates CD25(high)FOXP3(+)CTLA-4/CD152(+) and interleukin-10 producing Tregs inhibiting the response of CD4(+) and CD8(+) T lymphocytes. This inhibition is specific to the antigen presented, and only proliferating CD4(+) T lymphocytes express the Treg markers. Interleukin-10 is required for Treg induction by GILZ-expressing DCs. It is also needed for the suppressive function of Tregs. Antigen-presenting cells from patients treated with glucocorticoids generate interleukin-10-secreting Tregs ex vivo. These antigen-presenting cells produce GILZ, which is needed for Treg induction. Therefore, GILZ is critical for commitment of DCs to differentiate into regulatory DCs and to the generation of antigen-specific Tregs. This mechanism may contribute to the therapeutic effects of glucocorticoids. PMID- 17356132 TI - Human IL4I1 is a secreted L-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation. AB - Interleukin-4-induced gene 1 (IL4I1) was first described as a B-cell IL4 inducible gene and is highly expressed in primary mediastinal B-cell lymphomas. We established stable HEK293 clones expressing human and mouse IL4I1 to examine their biochemical properties and function. Both proteins were secreted into the culture medium, and we observed the secretion of endogenous human IL4I1 (hIL4I1) protein in a mediastinal lymphoma B-cell line, MedB-1. We showed that IL4I1 has l amino acid oxidase activity, optimal at physiological pH and primarily directed toward phenylalanine. Immunohistochemical analysis of secondary lymphoid organs showed staining of germinal center macrophages and inflammatory myeloid cells. In vitro, functional enzyme was highest in mature dendritic cells (DCs), suggesting a role in antigen-presenting cell/T-lymphocyte cross-talk. Indeed, hIL4I1 inhibited the proliferation of CD3-stimulated T lymphocytes with a similar effect on CD4(+) and CD8(+) T cells. In contrast, memory T cells were more strongly affected by hIL4I1 and its catabolite H(2)O(2) than naive T cells. hIL4I1 inhibitory effect was dependent on enzymatic activity and H(2)O(2) production and associated with a transient down-regulation of TCRzeta expression. Altogether these data suggest IL4I1 as a new immunomodulatory enzyme produced by DCs. PMID- 17356133 TI - Activation mechanisms of STAT5 by oncogenic Flt3-ITD. AB - Mutations in the receptor tyrosine kinase Flt3 represent a very common genetic lesion in acute myeloid leukemia (AML). Internal tandem duplication (ITD) mutations clustered in the juxtamembrane domain are the most frequent and best characterized mutations found in Flt3. Oncogenic activation of Flt3 by ITD mutations is known to activate aberrant signaling including activation of STAT5 and repression of myeloid transcription factors Pu.1 and c/EBP-alpha. However, the mechanisms of STAT5 activation by Flt3-ITD remain unclear. Using small molecule inhibitors and cell lines deficient for Src family kinases or Jak2 or Tyk2, here we show that Flt3-ITD-induced STAT5 activation is independent of Src or Jak kinases. Also, overexpression of SOCS1, an inhibitor of Jak kinases, inhibited IL-3- but not Flt3-ITD-mediated STAT5 activation. Furthermore, in vitro kinase assays revealed that STAT5 is a direct target of Flt3. Taken together, our data provide the mechanistic basis of STAT5 activation by Flt3-ITD. PMID- 17356135 TI - Complex regional pain syndrome with special emphasis on the knee. AB - Complex regional pain syndrome is characterised by an exaggerated response to injury in a limb with intense prolonged pain, vasomotor disturbance, delayed functional recovery and trophic changes. This review describes the current knowledge of the condition and outlines the methods of treatment available with particular emphasis on the knee. PMID- 17356134 TI - NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells. AB - The proteasome has been successfully targeted for the treatment of multiple myeloma and mantle cell lymphoma; however, in other hematologic malignancies, bortezomib has been less effective as a single agent. Here, we describe effects of NPI-0052, a novel proteasome inhibitor, in leukemia model systems. In cell lines, NPI-0052 inhibits all 3 proteolytic activities associated with the proteasome: chymotrypsin-, trypsin-, and caspase-like. NPI-0052 also induces DNA fragmentation in leukemia lines and in mononuclear cells from a Ph + acute lymphoblastic leukemia (ALL) patient. Caspase-3 activation by NPI-0052 was seen in wild-type Jurkat cells, but was significantly lessened in Fas-associated death domain (FADD)-deficient or caspase-8-deficient counterparts. NPI-0052-induced apoptosis was further probed using caspase-8 inhibitors, which were more protective than caspase-9 inhibitors. N-acetyl cysteine (NAC) also conferred protection against NPI-0052-induced apoptosis, indicating a role for oxidative stress by NPI-0052. In support of the drug's in vitro activities, biweekly treatment with NPI-0052 lessened total white blood cell (WBC) burden over 35 days in leukemic mice. Interestingly, combining NPI-0052 with either MS-275 or valproic acid (VPA) induced greater levels of cell death than the combination of bortezomib with these histone deacetylase inhibitors (HDACi). These effects of NPI-0052, alone and in combination with HDACi, warrant further testing to determine the compound's clinical efficacy in leukemia. PMID- 17356136 TI - Incomplete seating of the liner with the Trident acetabular system: a cause for concern? AB - We reviewed the initial post-operative radiographs of the Trident acetabulum and identified a problem with seating of the metal-backed ceramic liner. We identified 117 hips in 113 patients who had undergone primary total hip replacement using the Trident shell with a metal-backed alumina liner. Of these, 19 (16.4%) were noted to have incomplete seating of the liner, as judged by plain anteroposterior and lateral radiographs. One case of complete liner dissociation necessitating early revision was not included in the prevalence figures. One mis seated liner was revised in the early post-operative period and two that were initially incompletely seated were found on follow-up radiographs to have become correctly seated. There may be technical issues with regard to the implanting of this prosthesis of which surgeons should be aware. However, there is the distinct possibility that the Trident shell deforms upon implantation, thereby preventing complete seating of the liner. PMID- 17356137 TI - High rate of failure of impaction grafting in large acetabular defects. AB - We reviewed the results of 71 revisions of the acetabular component in total hip replacement, using impaction of bone allograft. The mean follow-up was 7.2 years (1.6 to 9.7). All patients were assessed according to the American Academy of Orthopedic Surgeons (AAOS) classification of bone loss, the amount of bone graft required, thickness of the graft layer, signs of graft incorporation and use of augmentation. A total of 20 acetabular components required re-revision for aseptic loosening, giving an overall survival of 72% (95% CI, 54.4 to 80.5). Of these failures, 14 (70%) had an AAOS type III or IV bone defect. In the failed group, poor radiological and histological graft incorporation was seen. These results suggest that impaction allografting in acetabular revision with severe bone defects may have poorer results than have previously been reported. PMID- 17356138 TI - Transplacental transfer of cobalt and chromium in patients with metal-on-metal hip arthroplasty: a controlled study. AB - Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry. Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 microg/l (0.55 to 2.55) and 1.28 microg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 microg/l (0.42 to 1.75) and 0.378 microg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p < 0.05). In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 microg/l (0.18 to 0.54) and 0.199 microg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 microg/l (0.17 to 0.5) and 0.194 microg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p > 0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p < 0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 microg/l) as in the controls (0.1934 microg/l), this difference was not statistically significant. (p > 0.05) The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer. PMID- 17356139 TI - Comparison of topical fibrin spray and tranexamic acid on blood loss after total knee replacement: a prospective, randomised controlled trial. AB - We performed a randomised, controlled trial involving 150 patients with a pre operative level of haemoglobin of 13.0 g/dl or less, to compare the effect of either topical fibrin spray or intravenous tranexamic acid on blood loss after total knee replacement. A total of 50 patients in the topical fibrin spray group had 10 ml of the reconstituted product applied intra-operatively to the operation site. The 50 patients in the tranexamic acid group received 500 mg of tranexamic acid intravenously five minutes before deflation of the tourniquet and a repeat dose three hours later, and a control group of 50 patients received no pharmacological intervention. There was a significant reduction in the total calculated blood loss for those in the topical fibrin spray group (p = 0.016) and tranexamic acid group (p = 0.041) compared with the control group, with mean losses of 1190 ml (708 to 2067), 1225 ml (580 to 2027), and 1415 ml (801 to 2319), respectively. The reduction in blood loss in the topical fibrin spray group was not significantly different from that achieved in the tranexamic acid group (p = 0.72). PMID- 17356140 TI - The Avon patellofemoral arthroplasty: five-year survivorship and functional results. AB - We report the mid-term results of a new patellofemoral arthroplasty for established isolated patellofemoral arthritis. We have reviewed the experience of 109 consecutive patellofemoral resurfacing arthroplasties in 85 patients who were followed up for at least five years. The five-year survival rate, with revision as the endpoint, was 95.8% (95% confidence interval 91.8% to 99.8%). There were no cases of loosening of the prosthesis. At five years the median Bristol pain score improved from 15 of 40 points (interquartile range 5 to 20) pre operatively, to 35 (interquartile range 20 to 40), the median Melbourne score from 10 of 30 points (interquartile range 6 to 15) to 25 (interquartile range 20 to 29), and the median Oxford score from 18 of 48 points (interquartile range 13 to 24) to 39 (interquartile range 24 to 45). Successful results, judged on a Bristol pain score of at least 20 at five years, occurred in 80% (66) of knees. The main complication was radiological progression of arthritis, which occurred in 25 patients (28%) and emphasises the importance of the careful selection of patients. These results give increased confidence in the use of patellofemoral arthroplasty. PMID- 17356141 TI - Early mobilisation after conventional knee replacement may reduce the risk of postoperative venous thromboembolism. AB - We carried out an audit on the result of achieving early walking in total knee replacement after instituting a new rehabilitation protocol, and assessed its influence on the development of deep-vein thrombosis as determined by Doppler ultrasound scanning on the fifth post-operative day. Early mobilisation was defined as beginning to walk less than 24 hours after knee replacement. Between April 1997 and July 2002, 98 patients underwent a total of 125 total knee replacements. They began walking on the second post-operative day unless there was a medical contraindication. They formed a retrospective control group. A protocol which allowed patients to start walking at less than 24 hours after surgery was instituted in August 2002. Between August 2002 and November 2004, 97 patients underwent a total of 122 total knee replacements. They formed the early mobilisation group, in which data were prospectively gathered. The two groups were of similar age, gender and had similar medical comorbidities. The surgical technique and tourniquet times were similar and the same instrumentation was used in nearly all cases. All the patients received low-molecular-weight heparin thromboprophylaxis and wore compression stockings post-operatively. In the early mobilisation group 90 patients (92.8%) began walking successfully within 24 hours of their operation. The incidence of deep-vein thrombosis fell from 27.6% in the control group to 1.0% in the early mobilisation group (chi-squared test, p < 0.001). There was a difference in the incidence of risk factors for deep-vein thrombosis between the two groups. However, multiple logistic regression analysis showed that the institution of an early mobilisation protocol resulted in a 30 fold reduction in the risk of post-operative deep-vein thrombosis when we adjusted for other risk factors. PMID- 17356142 TI - Accuracy analysis of Iso-C3D versus fluoroscopy-based navigated retrograde drilling of osteochondral lesions: a pilot study. AB - The aim of this pilot study was to evaluate the accuracy of two different methods of navigated retrograde drilling of talar lesions. Artificial osteochondral talar lesions were created in 14 cadaver lower limbs. Two methods of navigated drilling were evaluated by one examiner. Navigated Iso-C(3D) was used in seven cadavers and 2D fluoroscopy-based navigation in the remaining seven. Of 14 talar lesions, 12 were successfully targeted by navigated drilling. In both cases of inaccurate targeting the 2D fluoroscopy-based navigation was used, missing lesions by 3 mm and 5 mm, respectively. The mean radiation time was increased using Iso-C(3D) navigation (23 s; 22 to 24) compared with 2D fluoroscopy-based navigation (14 s, 11 to 17). PMID- 17356143 TI - Botulinum toxin type A as an adjunct to the surgical treatment of the medial rotation deformity of the shoulder in birth injuries of the brachial plexus. AB - We retrospectively reviewed 26 patients who underwent reconstruction of the shoulder for a medial rotation contracture after birth injury of the brachial plexus. Of these, 13 patients with a mean age of 5.8 years (2.8 to 12.9) received an injection of botulinum toxin type A into the pectoralis major as a surgical adjunct. They were matched with 13 patients with a mean age of 4.0 years (1.9 to 7.2) who underwent an identical operation before the introduction of botulinum toxin therapy to our unit. Pre-operatively, there was no significant difference (p = 0.093) in the modified Gilbert shoulder scores for the two groups. Post operatively, the patients who received the botulinum toxin had significantly better Gilbert shoulder scores (p = 0.012) at a mean follow-up of three years (1.5 to 9.8). It appears that botulinum toxin type A produces benefits which are sustained beyond the period for which the toxin is recognised to be active. We suggest that by temporarily weakening some of the power of medial rotation, afferent signals to the brain are reduced and cortical recruitment for the injured nerves is improved. PMID- 17356144 TI - GSB III total elbow replacement in rheumatoid arthritis. AB - Between 1993 and 2002, 58 GSB III total elbow replacements were implanted in 45 patients with rheumatoid arthritis by the same surgeon. At the most recent follow up, five patients had died (five elbows) and six (nine elbows) had been lost to follow-up, leaving 44 total elbow replacements in 34 patients available for clinical and radiological review at a mean follow-up of 74 months (25 to 143). There were 26 women and eight men with a mean age at operation of 55.7 years (24 to 77). At the latest follow-up, 31 excellent (70%), six good (14%), three fair (7%) and four poor (9%) results were noted according to the Mayo elbow performance score. Five humeral (11%) and one ulnar (2%) component were loose according to radiological criteria (type III or type IV). Of the 44 prostheses, two (5%) had been revised, one for type-IV humeral loosening after follow-up for ten years and one for fracture of the ulnar component. Seven elbows had post operative dysfunction of the ulnar nerve, which was transient in five and permanent in two. Despite an increased incidence of loosening with time, the GSB III prosthesis has given favourable mid-term results in patients with rheumatoid arthritis. PMID- 17356145 TI - High-energy extracorporeal shock-wave therapy for calcifying tendinitis of the rotator cuff: a randomised trial. AB - In a prospective randomised trial of calcifying tendinitis of the rotator cuff, we compared the efficacy of dual treatment sessions delivering 2500 extracorporeal shock waves at either high- or low-energy, via an electromagnetic generator under fluoroscopic guidance. Patients were eligible for the study if they had more than a three-month history of calcifying tendinitis of the rotator cuff, with calcification measuring 10 mm or more in maximum dimension. The primary outcome measure was the change in the Constant and Murley Score. A total of 80 patients were enrolled (40 in each group), and were re-evaluated at a mean of 110 (41 to 255) days after treatment when the increase in Constant and Murley score was significantly greater (t-test, p = 0.026) in the high-energy treatment group than in the low-energy group. The improvement from the baseline level was significant in the high-energy group, with a mean gain of 12.5 (-20.7 to 47.5) points (p < 0.0001). The improvement was not significant in the low-energy group. Total or subtotal resorption of the calcification occurred in six patients (15%) in the high-energy group and in two patients (5%) in the low-energy group. High energy shock-wave therapy significantly improves symptoms in refractory calcifying tendinitis of the shoulder after three months of follow-up, but the calcific deposit remains unchanged in size in the majority of patients. PMID- 17356146 TI - Interbody fusion with allograft and rhBMP-2 leads to consistent fusion but early subsidence. AB - We carried out a prospective study to determine whether the addition of a recombinant human bone morphogenetic protein (rhBMP-2) to a machined allograft spacer would improve the rate of intervertebral body fusion in the spine. We studied 77 patients who were to undergo an interbody fusion with allograft and instrumentation. The first 36 patients received allograft with adjuvant rhBMP-2 (allograft/rhBMP-2 group), and the next 41, allograft and demineralised bone matrix (allograft/demineralised bone matrix group). Each patient was assessed clinically and radiologically both pre-operatively and at each follow-up visit using standard methods. Follow-up continued for two years. Every patient in the allograft/rhBMP-2 group had fused by six months. However, early graft lucency and significant (> 10%) subsidence were seen radiologically in 27 of 55 levels in this group. The mean graft height subsidence was 27% (13% to 42%) for anterior lumbar interbody fusion, 24% (13% to 40%) for transforaminal lumbar interbody fusion, and 53% (40% to 58%) for anterior cervical discectomy and fusion. Those who had undergone fusion using allograft and demineralised bone matrix lost only a mean of 4.6% (0% to 15%) of their graft height. Although a high rate of fusion (100%) was achieved with rhBMP-2, significant subsidence occurred in more than half of the levels (23 of 37) in the lumbar spine and 33% (6 of 18) in the cervical spine. A 98% fusion rate (62 of 63 levels) was achieved without rhBMP-2 and without the associated graft subsidence. Consequently, we no longer use rhBMP 2 with allograft in our practice if the allograft has to provide significant structural support. PMID- 17356147 TI - Atypical mycobacterial spondylitis in HIV-negative patients identified by genotyping. AB - Non-tuberculous mycobacterial infections pose a significant diagnostic and therapeutic challenge. We report two cases of such infection of the spine in HIV negative patients who presented with deformity and neurological deficit. The histopathological features in both specimens were diagnostic of tuberculosis. The isolates were identified as Mycobacterium intracellulare and M. fortuitum by genotyping (MicroSeq 16S rDNA Full Gene assay) and as M. tuberculosis and a mycobacterium other than tuberculosis, respectively, by culture. There is a growing need for molecular diagnostic tools that can differentiate accurately between M. tuberculosis and atypical mycobacteria, especially in regions of the developing world which are experiencing an increase in non-tuberculous mycobacterial infections. PMID- 17356148 TI - Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. AB - We carried out a retrospective review over ten months of patients who had presented with a low-energy subtrochanteric fracture. We identified 13 women of whom nine were on long-term alendronate therapy and four were not. The patients treated with alendronate were younger, with a mean age of 66.9 years (55 to 82) vs 80.3 years (64 to 92) and were more socially active. The fractures sustained by the patients in the alendronate group were mainly at the femoral metaphyseal diaphyseal junction and many had occurred after minimal trauma. Five of these patients had prodromal pain in the affected hip in the months preceding the fall, and three demonstrated a stress reaction in the cortex in the contralateral femur. Our study suggests that prolonged suppression of bone remodelling with alendronate may be associated with a new form of insufficiency fracture of the femur. We believe that this finding is important and indicates the need for caution in the long-term use of alendronate in the treatment of osteoporosis. PMID- 17356149 TI - Monteggia fractures in adults: long-term results and prognostic factors. AB - The objective of this retrospective study was to correlate the Bado and Jupiter classifications with long-term results after operative treatment of Monteggia fractures in adults and to determine prognostic factors for functional outcome. Of 63 adult patients who sustained a Monteggia fracture in a ten-year period, 47 were available for follow-up after a mean time of 8.4 years (5 to 14). According to the Broberg and Morrey elbow scale, 22 patients (47%) had excellent, 12 (26%) good, nine (19%) fair and four (8%) poor results at the last follow-up. A total of 12 patients (26%) needed a second operation within 12 months of the initial operation. The mean Broberg and Morrey score was 87.2 (45 to 100) and the mean DASH score was 17.4 (0 to 70). There was a significant correlation between the two scores (p = 0.01). The following factors were found to be correlated with a poor clinical outcome: Bado type II fracture, Jupiter type IIa fracture, fracture of the radial head, coronoid fracture, and complications requiring further surgery. Bado type II Monteggia fractures, and within this group, Jupiter type IIa fractures, are frequently associated with fractures of the radial head and the coronoid process, and should be considered as negative prognostic factors for functional long-term outcome. Patients with these types of fracture should be informed about the potential risk of functional deficits and the possible need for further surgery. PMID- 17356150 TI - Giant-cell tumour of the knee: the condition of the cartilage after treatment by curettage and cementing. AB - We reviewed nine patients at a mean period of 11 years (6 to 16) after curettage and cementing of a giant-cell tumour around the knee to determine if there were any long-term adverse effects on the cartilage. Plain radiography, MRI, delayed gadolinium-enhanced MRI of the cartilage and measurement of the serum level of cartilage oligomeric matrix protein were carried out. The functional outcome was evaluated using the Lysholm knee score. Each patient was physically active and had returned to their previous occupation. Most participated in recreational sports or exercise. The mean Lysholm knee score was 92 (83 to 100). Only one patient was found to have cartilage damage adjacent to the cement. This patient had a history of intra-articular fracture and local recurrence, leading to degenerative changes. Interpretation of the data obtained from delayed gadolinium enhanced MRI of the cartilage was difficult, with variation in the T1 values which did not correlate with the clinical or radiological findings. We did not find it helpful in the early diagnosis of degeneration of cartilage. We also found no obvious correlation between the serum cartilage oligomeric matrix protein level and the radiological and MR findings, function, time after surgery and the age of the patient. In summary, we found no evidence that the long-term presence of cement close to the knee joint was associated with the development of degenerative osteoarthritis. PMID- 17356151 TI - Intercalary femoral reconstruction with extracorporeal irradiated autogenous bone graft in limb-salvage surgery. AB - Between 1996 and 2003, 16 patients (nine female, seven male) were treated for a primary bone sarcoma of the femur by wide local excision of the tumour, extracorporeal irradiation and re-implantation. An additional vascularised fibular graft was used in 13 patients (81%). All patients were free from disease when reviewed at a minimum of two years postoperatively (mean 49.7 months (24 to 96). There were no cases of infection. Primary union was achieved after a median of nine months (interquartile range 7 to 11). Five host-donor junctions (16%) united only after a second procedure. Primary union recurred faster at metaphyseal junctions (94% (15) at a median of 7.5 months (interquartile range 4 to 12)) than at diaphyseal junctions (75% (12) at a median of 11.1 months (interquartile range 5 to 18)). Post-operatively, the median Musculoskeletal Tumour Society score was 85% (interquartile range 75 to 96) and the median Toronto Extremity Salvage score 94% (interquartile range 82 to 99). The Mankin score gave a good or excellent result in 14 patients (88%). The range of movement of the knee was significantly worse when the extracorporeally irradiated autografts were fixed by plates rather than by nails (p = 0.035). A total of 16 (62%) of the junctions of the vascularised fibular grafts underwent hypertrophy, indicating union and loading. Extracorporeal irradiation autografting with supplementary vascularised fibular grafting is a promising biological alternative for intercalary reconstruction after wide resection of malignant bone tumours of the femur. PMID- 17356152 TI - Acetabuloplasty for neglected dislocation of the hip in older children. AB - This paper describes the technique and results of an acetabuloplasty in which the false acetabulum is turned down to augment the dysplastic true acetabulum at its most defective part. This operation was performed in 17 hips (16 children), with congenital dislocation and false acetabula. The mean age at operation was 5.1 years (4 to 8). The patients were followed clinically and radiologically for a mean of 6.3 years (5 to 10). A total of 16 hips had excellent results and there was one fair result due to avascular necrosis. The centre-edge angles and the obliquity of the acetabular roof improved in all cases, from a mean of -15.9 degrees (-19 degrees to 3 degrees ) and 42.6 degrees (33 degrees to 46 degrees ) to a mean of 29.5 degrees (20 degrees to 34 degrees ) and 11.9 degrees (9 degrees to 19 degrees ), respectively. The technique is not complex and is stable without internal fixation. It provides a near-normal acetabulum that requires minimal remodelling, and allows early mobilisation. PMID- 17356153 TI - Compliance with continuous passive movement is low after surgical treatment of idiopathic club foot in infants: a prospective, double-blinded clinical study. AB - Treatment by continuous passive movement at home is an alternative to immobilisation in a cast after surgery for club foot. Compliance with the recommended treatment, of at least four hours daily, is unknown. The duration of treatment was measured in 24 of 27 consecutive children with a mean age of 24 months (5 to 75) following posteromedial release for idiopathic club foot. Only 21% (5) of the children used the continuous passive movement machine as recommended. The mean duration of treatment at home each day was 126 minutes (11 to 496). The mean range of movement for plantar flexion improved from 15.2 degrees (10.0 degrees to 20.6 degrees ) to 18.7 degrees (10.0 degrees to 33.0 degrees ) and for dorsiflexion from 12.3 degrees (7.4 degrees to 19.4 degrees ) to 18.9 degrees (10.0 degrees to 24.1 degrees ) (both, p = 0.0001) when the first third of therapy was compared with the last third. A low level of patient compliance must be considered when the outcome after treatment at home is interpreted. PMID- 17356154 TI - Correction of neglected idiopathic club foot by the Ponseti method. AB - The Ponseti method of treating club foot has been shown to be effective in children up to two years of age. However, it is not known whether it is successful in older children. We retrospectively reviewed 17 children (24 feet) with congenital idiopathic club foot who presented after walking age and had undergone no previous treatment. All were treated by the method described by Ponseti, with minor modifications. The mean age at presentation was 3.9 years (1.2 to 9.0) and the mean follow-up was for 3.1 years (2.1 to 5.6). The mean time of immobilisation in a cast was 3.9 months (1.5 to 6.0). A painless plantigrade foot was obtained in 16 feet without the need for extensive soft-tissue release and/or bony procedures. Four patients (7 feet) had recurrent equinus which required a second tenotomy. Failure was observed in five patients (8 feet) who required a posterior release for full correction of the equinus deformity. We conclude that the Ponseti method is a safe, effective and low-cost treatment for neglected idiopathic club foot presenting after walking age. PMID- 17356155 TI - Benign solitary schwannomas: a review of 234 cases. AB - We reviewed 234 benign solitary schwannomas treated between 1984 and 2004. The mean age of the patients was 45.2 years (11 to 82). There were 170 tumours (73%) in the upper limb, of which 94 (40%) arose from the brachial plexus or other nerves within the posterior triangle of the neck. Six (2.6%) were located within muscle or bone. Four patients (1.7%) presented with tetraparesis due to an intraspinal extension. There were 198 primary referrals (19 of whom had a needle biopsy in the referring unit) and in these patients the tumour was excised. After having surgery or an open biopsy at another hospital, a further 36 patients were seen because of increased neurological deficit, pain or incomplete excision. In these, a nerve repair was performed in 18 and treatment for pain or paralysis was offered to another 14. A tender mass was found in 194 (98%) of the primary referrals. A Tinel-like sign was recorded in 155 (81%). Persistent spontaneous pain occurred in 60 (31%) of the 194 with tender mass, impairment of cutaneous sensibility in 39 (20%), and muscle weakness in 24 (12%). After apparently adequate excision, two tumours recurred. No case of malignant transformation was seen. PMID- 17356156 TI - Adamantinoma of the tibia with late skeletal metastasis: an unusual presentation. AB - Adamantinoma is a rare tumour of long bones that occurs most commonly in the tibia. Its pathogenesis is unknown. It is locally aggressive and recurrences are common after resection. Metastases have been reported in 10% to 20% of cases, most commonly in the lungs and rarely in the lymph nodes. We report a patient who developed a skeletal metastasis four years after resection of the primary tumour. There was no evidence of recurrence at the primary site or of secondary deposits in the lungs. PMID- 17356157 TI - Intertrochanteric fracture of an arthrodesed hip. AB - We report the case of a 74-year-old woman who sustained an intertrochanteric fracture of the femoral neck in a previously arthrodesed hip. The hip arthrodesis had been performed 53 years earlier to treat septic arthritis. The fracture was treated successfully using a double-plating technique with 4.5 mm titanium reconstruction plates. PMID- 17356158 TI - Fractures of Corin 'Taper-Fit' CDH stems used in 'cement-in-cement' revision total hip replacement. AB - We describe two cases of fracture of Corin Taper-Fit stems used for cement-in cement revision of congenital dysplasia of the hip. Both prostheses were implanted in patients in their 50s, with high offsets (+7.5 mm and +3.5 mm), one with a large diameter (48 mm) head and one with a constrained acetabular component. Fracture of the stems took place at nine months and three years post operatively following low-demand activity. Both fractures occurred at the most medial of the two stem introducer holes in the neck of the prosthesis, a design feature that is unique to the Taper-Fit stem. We would urge caution in the use of these particular stems for cement-in-cement revisions. PMID- 17356159 TI - Remodelling of the distal radius after epiphysiolysis and lengthening. AB - Arrest of growth of the distal radius is rare but will produce deformity of the wrist. We corrected angular deformity and shortening of the distal radius by epiphysiolysis and gradual lengthening without a corrective osteotomy. PMID- 17356160 TI - Patellar tendon lengthening for patella infera using the Ilizarov technique. AB - Patella infera can cause knee pain and lead to patellofemoral osteoarthritis. Treatment is usually unsatisfactory. We describe a case of severe patella infera after operative treatment for fracture of the patella. We used Ilizarov external fixation and gradual lengthening of the patellar tendon. The patellar height was restored and the patient's symptoms were much improved. PMID- 17356161 TI - Effect of vitamin C on fracture healing in elderly Osteogenic Disorder Shionogi rats. AB - We studied the effect of vitamin C on fracture healing in the elderly. A total of 80 elderly Osteogenic Disorder Shionogi rats were divided into four groups with different rates of vitamin C intake. A closed bilateral fracture was made in the middle third of the femur of each rat. Five weeks after fracture the femora were analysed by mechanical and histological testing. The groups with the lower vitamin C intake demonstrated a lower mechanical resistance of the healing callus and a lower histological grade. The vitamin C levels in blood during healing correlated with the torque resistance of the callus formed (r = 0.525). Therefore, the supplementary vitamin C improved the mechanical resistance of the fracture callus in elderly rats. If these results are similar in humans, vitamin C supplementation should be recommended during fracture healing in the elderly. PMID- 17356162 TI - The effect of the design of the femoral component on the conformity of the patellofemoral joint in total knee replacement. AB - One of the most controversial issues in total knee replacement is whether or not to resurface the patella. In order to determine the effects of different designs of femoral component on the conformity of the patellofemoral joint, five different knee prostheses were investigated. These were Low Contact Stress, the Miller-Galante II, the NexGen, the Porous-Coated Anatomic, and the Total Condylar prostheses. Three-dimensional models of the prostheses and a native patella were developed and assessed by computer. The conformity of the curvature of the five different prosthetic femoral components to their corresponding patellar implants and to the native patella at different angles of flexion was assessed by measuring the angles of intersection of tangential lines. The Total Condylar prosthesis had the lowest conformity with the native patella (mean 8.58 degrees ; 0.14 degrees to 29.9 degrees ) and with its own patellar component (mean 11.36 degrees ; 0.55 degrees to 39.19 degrees ). In the other four prostheses, the conformity was better (mean 2.25 degrees ; 0.02 degrees to 10.52 degrees ) when articulated with the corresponding patellar component. The Porous-Coated Anatomic femoral component showed better conformity (mean 6.51 degrees ; 0.07 degrees to 9.89 degrees ) than the Miller-Galante II prosthesis (mean 11.20 degrees ; 5.80 degrees to 16.72 degrees ) when tested with the native patella. Although the Nexgen prosthesis had less conformity with the native patella at a low angle of flexion, this improved at mid (mean 3.57 degrees ; 1.40 degrees to 4.56 degrees ) or high angles of flexion (mean 4.54 degrees ; 0.91 degrees to 9.39 degrees ), respectively. The Low Contact Stress femoral component had the best conformity with the native patella (mean 2.39 degrees ; 0.04 degrees to 4.56 degrees ). There was no significant difference (p > 0.208) between the conformity when tested with the native patella or its own patellar component at any angle of flexion. The geometry of the anterior flange of a femoral component affects the conformity of the patellofemoral joint when articulating with the native patella. A more anatomical design of femoral component is preferable if the surgeon decides not to resurface the patella at the time of operation. PMID- 17356163 TI - Validation of the lesser sigmoid notch of the ulna as a reference point for accurate placement of a prosthesis for the head of the radius: a cadaver study. AB - We undertook a study on eight arms from fresh cadavers to define the clinical usefulness of the lesser sigmoid notch as a landmark when reconstructing the length of the neck of the radius in replacement of the head with a prosthesis. The head was resected and its height measured, along with several control measurements. This was compared with in situ measurements from the stump of the neck to the proximal edge of the lesser sigmoid notch of the ulna. All the measurements were performed three times by three observers acting independently. The results were highly reproducible with intra- and interclass correlations of > 0.99. The mean difference between the measurement on the excised head and the distance from the stump of the neck and the lesser sigmoid notch was -0.02 mm ( 1.24 to +0.97). This difference was not statistically significant (p = 0.78). The proximal edge of the lesser sigmoid notch provides a reliable landmark for positioning a replacement of the radial head and may have clinical application. PMID- 17356164 TI - Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances: an in vitro study. AB - Platelet-rich plasma is a new inductive therapy which is being increasingly used for the treatment of the complications of bone healing, such as infection and nonunion. The activator for platelet-rich plasma is a mixture of thrombin and calcium chloride which produces a platelet-rich gel. We analysed the antibacterial effect of platelet-rich gel in vitro by using the platelet-rich plasma samples of 20 volunteers. In vitro laboratory susceptibility to platelet rich gel was determined by the Kirby-Bauer disc-diffusion method. Baseline antimicrobial activity was assessed by measuring the zones of inhibition on agar plates coated with selected bacterial strains. Zones of inhibition produced by platelet-rich gel ranged between 6 mm and 24 mm (mean 9.83 mm) in diameter. Platelet-rich gel inhibited the growth of Staphylococcus aureus and was also active against Escherichia coli. There was no activity against Klebsiella pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa. Moreover, platelet rich gel seemed to induce the in vitro growth of Ps. aeruginosa, suggesting that it may cause an exacerbation of infections with this organism. We believe that a combination of the inductive and antimicrobial properties of platelet-rich gel can improve the treatment of infected delayed healing and nonunion. PMID- 17356166 TI - Infection in knee replacements after previous injection of intra-articular steroid. PMID- 17356167 TI - Infection in knee replacements after previous injection of intra-articular steroid. PMID- 17356168 TI - Infection in knee replacements after previous injection of intra-articular steroid. PMID- 17356169 TI - Allocation of paraventricular and supraoptic neurons requires Sim1 function: a role for a Sim1 downstream gene PlexinC1. AB - SIM1 is a transcription factor essential for the developmental expression of the endocrine hormone genes, e.g. vasopressin (Vp) and oxytocin (Ot), in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Mice mutant for Sim1 lack structural PVN and SON, attributed in previous studies to the death of the PVN/SON progenitor cells. Here, we use a tau-LacZ knock-in allele at the Sim1 locus to trace Sim1 mutant cells and show that they are generated normally and survive to birth, contrasting to the previous proposal. Mutant cells adopt neuronal characteristics and maintain their PVN/SON identity as they continue to express PVN/SON progenitor markers. However, they occupy an ectopic position between the normal PVN and SON, indicating a defect in neuronal migration. To explore candidate molecular cues that contribute to PVN/SON neuronal migration, we focused on the Plexin family of genes. We found that PlexinA1 is expressed in regions surrounding the PVN and SON, whereas PlexinC1 is expressed within the PVN and SON. PlexinA1 expression becomes up-regulated in Sim1 mutant cells, whereas PlexinC1 expression is down-regulated. Finally, the PlexinC1 mutant has a selective defect in partitioning the VP and OT neurons coherently into the PVN and SON. Together, our results uncover a transcriptional regulation of neuronal migration cues initiated by Sim1 that contribute to the organization of the PVN and SON. PMID- 17356170 TI - A structural and in vitro characterization of asoprisnil: a selective progesterone receptor modulator. AB - Selective progesterone receptor modulators (SPRMs) have been suggested as therapeutic agents for treatment of gynecological disorders. One such SPRM, asoprisnil, was recently in clinical trials for treatment of uterine fibroids and endometriosis. We present the crystal structures of progesterone receptor (PR) ligand binding domain complexed with asoprisnil and the corepressors nuclear receptor corepressor (NCoR) and SMRT. This is the first report of steroid nuclear receptor crystal structures with ligand and corepressors. These structures show PR in a different conformation than PR complexed with progesterone (P4). We profiled asoprisnil in PR-dependent assays to understand further the PR-mediated mechanism of action. We confirmed previous findings that asoprisnil demonstrated antagonism, but not agonism, in a PR-B transfection assay and the T47D breast cancer cell alkaline phosphatase activity assay. Asoprisnil, but not RU486, weakly recruited the coactivators SRC-1 and AIB1. However, asoprisnil strongly recruited the corepressor NCoR in a manner similar to RU486. Unlike RU486, NCoR binding to asoprisnil-bound PR could be displaced with equal affinity by NCoR or TIF2 peptides. We further showed that it weakly activated T47D cell gene expression of Sgk-1 and PPL and antagonized P4-induced expression of both genes. In rat leiomyoma ELT3 cells, asoprisnil demonstrated partial P4-like inhibition of cyclooxygenase (COX) enzymatic activity and COX-2 gene expression. In the rat uterotrophic assay, asoprisnil demonstrated no P4-like ability to oppose estrogen. Our data suggest that asoprisnil differentially recruits coactivators and corepressors compared to RU486 or P4, and this specific cofactor interaction profile is apparently insufficient to oppose estrogenic activity in rat uterus. PMID- 17356172 TI - Flux at focal adhesions: slippage clutch, mechanical gauge, or signal depot. AB - Focal adhesions provide physical linkages between the interior of an adhesive cell and the extracellular matrix (ECM). They may be involved in mediating such functions as cell migration, anchorage, mechanical interactions with the ECM, and the detection of physical cues in the environment. Cell biologists have long struggled to piece together the complex array of components found at focal adhesions, and the equally complex network of interactions among these components, into a "machine" that performs these putative functions. Two recent studies, however, indicate that focal adhesions may be more amorphous and dynamic than previously envisioned. These studies found different degrees of correlated retrograde movement of various focal adhesion proteins with actin filaments, while integrins remained largely stationary. Such differential movements appear inconsistent with a precisely engineered machine and may reflect a slippage clutch for transmitting a variable amount of contractile force to the substrate for migration, a gauge of physical interactions at adhesive sites, or a mechanism for releasing signals from the adhesive sites to the interior of the cell. PMID- 17356171 TI - Alien interacts with the human androgen receptor and inhibits prostate cancer cell growth. AB - Prostate cancer cell growth is initially androgen dependent. Androgen antagonists are used in prostate cancer therapy to inactivate the transcriptional activity of the human androgen receptor (hAR) and to inhibit the proliferation of prostate cancer. Here, we have characterized Alien with characteristics of a corepressor as a novel interacting factor for the antagonist bound hAR. Alien is recruited to hAR in the presence of the AR antagonist cyproterone acetate (CPA). The interaction of Alien with hAR is verified in vivo and in vitro by a modified mammalian two-hybrid system, coimmunoprecipitation, chromatin immunoprecipitation, and in vitro binding assays. In contrast to other nuclear receptors, Alien binds to the amino-terminus of hAR with the receptor SUMOylation (small ubiquitin modifier) sites being involved. Furthermore, cellular localization of Alien is changed towards a predominant nuclear localization upon treatment of prostate cancer cells with CPA. Notably, stable expression of Alien in LNCaP cells inhibits both endogenous prostate-specific antigen expression and proliferation of these cells in the presence of CPA but not in the presence of an AR agonist. These findings underline the importance of corepressors for inhibition of prostate cancer cell growth by androgen antagonists. PMID- 17356173 TI - The expanding role for ITAM-based signaling pathways in immune cells. AB - The immunoreceptor tyrosine-based activation motif (ITAM) is the primary signaling domain used by classical immunoreceptors, such as the antigen receptors on B and T lymphocytes and the Fc receptors (FcRs) on myeloid cells. The ITAM is contained in the intracellular region of subunits associated with these receptors, often in pairs, or is part of the cytoplasmic domain of the receptors themselves. Data from many investigators have demonstrated that ITAMs are both necessary and sufficient for initiation of signaling downstream of all immunoreceptors. More recent reports indicate that ITAM signaling is used by additional receptors beyond the classical immunoreceptors: Cell adhesion molecules (integrins and PSGL-1), chemokine receptors (CXCR4), plexins, and lectin receptors all mediate immune cell function through ITAM-like signaling pathways. This convergence of intracellular signaling pathways in leukocytes illuminates the importance of tyrosine-based activation motifs in the immune system and suggests that inhibitors of ITAM signaling may have broader effects than originally envisioned. PMID- 17356174 TI - Transition from screen-film to digital radiography: evolution of patient radiation doses at projection radiography. AB - PURPOSE: To retrospectively evaluate patient radiation doses in projection radiography after the transition to computed radiography (CR) in the authors' hospital. MATERIALS AND METHODS: The hospital's ethical committee approved the study and waived informed consent. In 2001, a dose reduction initiative was implemented, which involved collecting radiographic parameters, calculating patient entrance doses, and monitoring changes with an online computer, and a training program for radiographers was conducted. A database with 204 660 patient dose values was used to compute changes in patient doses over time. Sample sizes ranged from 1800 to 23 000 examinations. Doses were compared with European and American reference values. Kruskal-Wallis and Mann-Whitney tests were used for statistical analysis. RESULTS: Median values for patient entrance doses increased 40%-103% after implementation of CR. Initial increases were corrected during the 1st year, and additional dose decreases were achieved after the dose reduction initiative was launched. At present, doses range between 15% and 38% of the European diagnostic reference levels established for screen-film radiography and between 28% and 41% of the reference values recommended by the American Association of Physicists in Medicine, representing an effective 20%-50% reduction in the initial values for CR. CONCLUSION: Though patient doses can increase considerably during the transition from conventional screen-film radiography to CR, dose management programs, including specific training of radiographers and patient dose audits, allow for reductions of the previous values. PMID- 17356175 TI - Hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: helical CT and MR imaging findings with clinical-pathologic comparison. AB - PURPOSE: To retrospectively evaluate the clinical, pathologic, and helical computed tomographic (CT) and magnetic resonance (MR) imaging findings of hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Institutional review board approval was obtained for this study; the need for patient informed consent was waived. Clinical, pathologic, and imaging findings were retrospectively evaluated in 22 men (mean age, 64.5 years) with HCC and NAFLD. Helical CT and MR images were reviewed for morphologic features such as tumor size, margins, necrosis, and degree of enhancement. RESULTS: Obesity, diabetes, and hypertension were common findings and were observed in 12 (55%), 14 (64%), and 13 (59%) of the 22 patients, respectively. The serum alpha-fetoprotein level was elevated in eight patients (36%). All patients had pathologic evidence of NAFLD. HCC was well-differentiated in seven patients, moderately differentiated in 11, and poorly differentiated in four. Large tumors (mean diameter, 8.4 cm) were depicted at CT and/or MR imaging in all patients. Twenty-one patients had a solitary or dominant mass. At imaging, tumor margins were well defined in 17 patients, with a smooth surface in 17, and there was evidence of a tumor capsule in 15. Necrosis was depicted in 16 patients. There was no evidence of calcifications, central scar, fat, or abdominal lymphadenopathy. CT was performed in 20 patients. HCC was hypoattenuating on unenhanced CT scans in 14 patients, heterogeneously hyperattenuating in the arterial phase in 20, and hypoattenuating in the portal phase in 14. MR imaging was performed in 16 patients. HCC was hyperintense compared with liver parenchyma at T2-weighted MR imaging in all 16 patients, hypointense at T1-weighted imaging in 14, heterogeneously hyperintense at arterial phase T1-weighted imaging in 16, and hypointense at portal phase T1 weighted imaging in 14. CONCLUSION: HCC in patients with NAFLD is more likely to manifest as a large solitary or dominant mass characterized by smooth and possibly encapsulated margins, necrosis, and hypervascularity. PMID- 17356176 TI - Changes of intratumoral microvessels and blood perfusion during establishment of hepatic metastases in mice. AB - PURPOSE: To prospectively evaluate the stepwise changes that occur in intratumoral microvessels and microcirculation during the establishment of murine colonic hepatic metastases by using in vivo fluorescent microscopy and to compare the changes with tumor angiogenesis evaluated with an immunohistochemical study. MATERIALS AND METHODS: This study was approved by the institutional animal care and use committee. Twenty-five mice with hepatic metastases created with injection of murine colonic adenocarcinoma (colon 26) tumor cells into the spleen were examined with in vivo microscopy and immunohistochemical study for CD34, intracellular adhesion molecule (ICAM-1), and alpha smooth muscle actin (alpha SMA). The tumor size, microcirculation in tumors, intratumoral microvessel density (MVD), afferent MVD, and CD34-positive MVD were evaluated. The data among the tumors that showed different hemodynamic or immunohistochemical patterns were compared with the Kruskal-Wallis test and the Student t test. RESULTS: Four stepwise patterns were observed according to the changes in morphology, hemodynamics, and immunohistochemical characteristics of intratumoral microvessels during the establishment of hepatic metastases, as follows: metastases without definite intratumoral blood perfusion or any intratumoral microvessels (mean diameter, approximately 180 microm), metastases with portal perfusion and intratumoral ICAM-1-positive residual hepatic sinusoids (mean diameter, approximately 290 microm), metastases with mixed portal and arterial perfusion and increased CD34-positive microvessels and alpha-SMA-positive arterioles (mean diameter, approximately 520 microm), and metastases with exclusively arterial perfusion and increased CD34-positive microvessels and alpha SMA-positive arterioles (mean diameter, >2000 microm). The differences among the mean sizes of the tumors that showed these four patterns were statistically significant (P < .01). CONCLUSION: Stepwise changes of intratumoral microcirculation were revealed from direct diffusion, to portal perfusion, to mixed portal and arterial perfusion, and finally to arterial perfusion in accordance with stepwise tumor neovascularization during the growth of murine colonic hepatic metastases. PMID- 17356177 TI - Malignant supratentorial astrocytoma treated with postoperative radiation therapy: prognostic value of pretreatment quantitative diffusion-weighted MR imaging. AB - PURPOSE: To retrospectively evaluate whether the minimum apparent diffusion coefficient (ADC) of the tumor seen on pretreatment magnetic resonance (MR) images is of prognostic value in patients with malignant supratentorial astrocytoma. MATERIALS AND METHODS: The study was approved by the institutional review board; the requirement for informed patient consent was waived. Between June 1996 and November 2003, 79 patients (44 male, 35 female; age range, 16-76 years) with malignant supratentorial astrocytoma underwent pretreatment MR imaging. Patient age, symptom duration, neurologic function, mental status, Karnofsky performance scale (KPS) score, extent of surgery, histopathologic diagnosis, tumor component enhancement, and minimum ADC were assessed at factor analysis of survival. Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) criteria were used to validate the prognostic value of the minimum ADC. Kaplan-Meier survival curves, the log-rank test, and the multivariate Cox proportional hazards model were used to evaluate the prognostic factors. RESULTS: Twenty-nine patients had anaplastic astrocytoma, and 50 had glioblastoma multiforme. The minimum ADC was significantly lower in patients with glioblastoma multiforme than in those with anaplastic astrocytoma (P < .001). The two-year survival rates associated with low (1.0 x 10(-3) mm(2)/sec) minimum ADCs were 14% (six of 42 patients) and 84% (31 of 37 patients), respectively (P < .001). The minimum ADC was the most important prognostic factor (hazard ratio = 10.459; 95% confidence interval: 5.113, 21.396) and could be used to assign patients to different prognostic groups in each RTOG RPA class. CONCLUSION: The minimum ADC at pretreatment MR imaging is a useful clinical prognostic biomarker for survival in patients with malignant supratentorial astrocytoma. PMID- 17356178 TI - Digital mammography: effects of reduced radiation dose on diagnostic performance. AB - PURPOSE: To experimentally determine the relationship between radiation dose and observer accuracy in the detection and discrimination of simulated lesions for digital mammography. MATERIALS AND METHODS: This HIPAA-compliant study received institutional review board approval; the informed consent requirement was waived. Three hundred normal craniocaudal images were selected from an existing database of digital mammograms. Simulated mammographic lesions that mimicked benign and malignant masses and clusters of microcalcifications (3.3-7.4 cm in diameter) were then superimposed on images. Images were rendered without and with added radiographic noise to simulate effects of reducing the radiation dose to one half and one quarter of the clinical dose. Images were read by five experienced breast imaging radiologists. Results were analyzed to determine effects of reduced dose on overall interpretation accuracy, detection of microcalcifications and masses, discrimination between benign and malignant masses, and interpretation time. RESULTS: Overall accuracy decreased from 0.83 with full dose to 0.78 and 0.62 with half and quarter doses, respectively. The decrease associated with transition from full dose to quarter dose was significant (P < .01), primarily because of an effect on detection of microcalcifications (P < .01) and discrimination of masses (P < .05). The level of dose reduction did not significantly affect detection of malignant masses (P > .5). However, reduced dose resulted in an increased mean interpretation time per image by 28% (P < .0001). CONCLUSION: These findings suggest that dose reduction in digital mammography has a measurable but modest effect on diagnostic accuracy. The small magnitude of the effect in response to the drastic reduction of dose suggests potential for modest dose reductions in digital mammography. PMID- 17356179 TI - Using propensity scoring to estimate program-related subgroup impacts in experimental program evaluations. AB - This article discusses the use of propensity scoring in experimental program evaluations to estimate impacts for subgroups defined by program features and participants' program experiences. The authors discuss estimation issues and provide specification tests. They also discuss the use of an overlooked data collection design--obtaining predictions that program intake staff make about applicants' likely program assignments and experiences--that could improve the quality of matched comparison samples. They demonstrate the effectiveness of this approach in producing credible subgroup findings using data from a large-scale experimental evaluation of Job Corps, the nation's largest federal education and training program for disadvantaged youths. PMID- 17356180 TI - Before you open the doors: ten lessons from Florida's Faith and Community-Based Delinquency Treatment Initiative. AB - In 2003, the Office of Juvenile Justice and Delinquency Prevention (OJJDP) provided Florida's Department of Juvenile Justice (DJJ) with a $3.5 million grant to design and implement a faith- and community-based program for incarcerated juveniles. Florida's experience developing a completely new program has provided valuable lessons regarding important issues to consider and address before clients are referred to the program. This article enumerates 10 key lessons from Florida's experience that can provide important guidance to other sites across the country hoping to develop faith-related services for youths in institutions. PMID- 17356181 TI - Issues, challenges, and solutions in translating study instruments. AB - Cross-cultural adaptation of study instruments is a difficult, time-consuming, but arguably cost-effective process. If conducted properly, it has the advantage that the translated study instruments are accurate, easy to understand, accessible, and culturally appropriate to the target audience and produce reliable and valid data. This article explores issues, challenges, and solutions for translating a set of research instruments used in a randomized, controlled trial for four separate community languages (Chinese, Vietnamese, Greek, Italian). PMID- 17356182 TI - A repeated observation approach for estimating the street homeless population. AB - Risks of life on the street caused by inclement weather, harassment, and assault threaten the unsheltered homeless population. We address some challenges of enumerating the street homeless population by testing a novel capture-recapture (CR) estimation approach that models individuals' intermittent daytime visibility. We tested walking and vehicle-based variants of CR in downtown Toronto in March. Estimates that assume individual variability of sighting probabilities are most consistent with our knowledge of the homeless and achieve the most favorable confidence intervals, estimated detection probabilities, and coefficient of variation. Estimation bias from interobserver discrepancies, duplicate counting, and violation of the closed population assumption were minimized with uniform identification criteria, training, and sampling design. Bias caused by the social grouping of the homeless was small. Despite the limitations of visual identification, CR approaches as part of a multiple-method program can aid community responses to immediate needs on the street, especially during the harsh winter months. PMID- 17356183 TI - Improving care for patients with diabetes: the role of simple reminders. PMID- 17356185 TI - Arginine vasopressin as a supplementary vasopressor in refractory hypertensive, hypervolemic, hemodilutional therapy in subarachnoid hemorrhage. AB - INTRODUCTION: Hypertensive, hypervolemic, and hemodilutional (HHH) therapy for vasospasm in subarachnoid hemorrhage (SAH) refractory to phenylephrine requires high doses of catecholamines, leading to adverse adrenergic effects. Arginine vasopressin (AVP) has been shown to stabilize advanced shock states while facilitating reduction of catecholamine doses, but its use has never been reported in SAH. In this retrospective study, we investigated the hemodynamic effects and feasibility of supplementary AVP in refractory HHH therapy in SAH. METHODS: Hemodynamic response (mean arterial pressure [MAP], heart rate, central venous pressure, cardiac index, systemic vascular resistance index, and end diastolic volume index) to a supplementary AVP infusion (0.01-0.04 IU/minute) was recorded within the first 24 hours in 22 patients. Secondary endpoints (serum sodium concentration, incidence of vasospasm, and intracranial pressure [ICP]) were compared to controls on HHH therapy with phenylephrine alone. RESULTS: After initiation of AVP, MAP increased significantly compared to baseline. Phenylephrine doses decreased significantly, whereas other hemodynamic parameters remained stable. Serum sodium concentrations decreased similarly in both groups ( 5 +/- 7 mmol/L versus -6 +/- 4 mmol/L; p = 0.25). No detrimental effects on vasospasm incidence or ICP and cerebral perfusion pressure were noted. CONCLUSION: AVP may be considered as an alternative supplementary vasopressor in refractory HHH therapy with phenylephrine in SAH. Although we did not observe any deleterious effect of AVP on cerebral circulation, close observation for development of cerebral vasospasm should be undertaken, until it is clearly demonstrated that AVP has no adverse effects on regional cerebral blood flow and symptomatic cerebral vasospasm. Our limited data suggest that low-dose AVP does not cause brain edema, but further study is merited. PMID- 17356186 TI - The Merci Retrieval System for acute stroke: the Southeast Regional Stroke Center experience. AB - INTRODUCTION: The Merci Retrieval System was cleared for use in patients with stroke in August 2004. However, there are few published results of "real world experience" with the device. METHODS: We captured single-center data on 25 consecutive patients with acute ischemic stroke treated with the Merci Retrieval System according to the MERCI trial except that we treated some patients with tandem proximal carotid and intracranial lesions with carotid angioplasty and stenting and some patients were treated within the 3-hour window. RESULTS: Median patient age was 63 years and median initial National Institute of Health Stroke Scale (NIHSS) score was 18. Isolated M1 or M2 middle cerebral artery lesions occurred in 52%, "carotid T" lesions in 8%, and vertebrobasilar lesions in 8%. Tandem lesions involving proximal carotid and proximal intracranial vessel occurred in 32%, necessitating emergent multilevel treatment including carotid stenting. Median duration from symptom onset to Merci device utilization was 5.2 hours. Successful reperfusion (> or = thrombolysis in myocardial infarction [TIMI] 2 flow) in the target vessel was obtained in 56% of cases. Statistical analysis revealed a strong correlation between ability to achieve greater than or equal to TIMI 2 flow and good clinical outcome as measured by 3-month NIHSS score, modified Rankin Scale (mRS), and mortality (nine out of the 12 without successful reperfusion died compared to none of the 13 with > or =TIMI 2 flow, p < 0.001). Younger age and lower NIHSS score on presentation were also predictors of good clinical outcome at 3 months. CONCLUSION: These "real world data" demonstrate that the results of the previous MERCI trial can be "independently replicated" at a regional stroke center. Although the results of placebo controlled trials are still pending, mechanical revascularization has become a critical component of our acute stroke protocol, particularly for severe strokes. Issues still remain regarding recalcitrant lesions and operator experience, which necessitate further clinical testing and device optimization. PMID- 17356188 TI - Rapid geographical clustering of wound botulism in Germany after subcutaneous and intramuscular injection of heroin. AB - BACKGROUND: Wound infections due to Clostridium botulinum in Germany are rare and occur predominantly in heroin injectors, especially after subcutaneous or intramuscular injection of heroin ("skin popping"), which is contaminated with spores of C. botulinum. We report a rapid geographical clustering of cases in Germany in a region between Cologne, Bonn, and Aachen with wound botulism and consecutive systemic C. botulinum intoxication in intravenous drug users (IDUs) within 6 weeks in October and November 2005. PATIENTS: A group of 12 IDUs with wound botulism after "skin popping." RESULTS: Clinical data were available in 11 (92%) of 12 patients; in 7 (58%) of the 12 cases, there was cranial nerve involvement including mydriasis, diplopia, dysarthria, and dysphagia, followed by progressing symmetric and flaccid paralysis of proximal muscles of the neck, arms, trunk, and respiratory muscles. Mechanical respiratory support was necessary. Five of the IDUs were treated with antitoxin, but mechanical respiratory support could not be avoided. The mean ventilation duration was 27.4 days (range 6-77 days). In 4 patients (33%), mechanical ventilation could be avoided; two were treated with antitoxin. CONCLUSIONS: This report describes rapid geographical clustering of wound botulism with severe respiratory complications in IDUs after "skin popping," which has not previously been reported either in Germany or any other European country. Based on these observations and those in other European countries, we conclude that there is a trend towards "skin popping," suggesting a change in injection practices in IDUs. Secondly, we conclude that the total number of cases with wound botulism is likely to increase because "skin popping" is the main risk factor. PMID- 17356187 TI - Frameless stereotactic aspiration and thrombolysis of deep intracerebral hemorrhage is associated with reduced levels of extracellular cerebral glutamate and unchanged lactate pyruvate ratios. AB - INTRODUCTION: Intracerebral hemorrhage (ICH) is a devastating form of stroke commonly resulting in severe morbidity and high mortality. Secondary brain injury often occurs in the days following the initial hemorrhage and is associated with significant neurological deterioration. The neurochemistry associated with secondary injury is poorly understood. The purpose of this study is to characterize the neurochemical changes in perihematomal tissue during frameless minimally invasive evacuation of spontaneous hematomas. METHODS: This is a nonrandomized prospective microdialysis study of 12 consecutive patients undergoing Frameless Stereotactic Aspiration and Thrombolysis (FAST) of deep ICHs. Hourly glucose, lactate, pyruvate, and glutamate were measured in the perihematomal tissue of patients undergoing minimally invasive hematoma evacuation. Analyte concentrations were compared to evaluate the natural history of perihematomal neurochemistry and to identify changes potentially related to secondary injury. RESULTS: Brain hematoma volumes were reduced 87% during FAST and National Institute of Health Stroke Scale (NIHSS) scores were improved from an average of 19 at admission to 12.6 at time of discharge from the intensive care unit. Glutamate average values decreased from the first 24 hours of measurement (12 mmol/L +/- 6) to the final 24-hour epoch (5 mmol/L +/- 6). Glutamate reduction showed a significant linear (p = 0.0007) and quadratic (p <0.05) trend during hematoma drainage. Lactate pyruvate ratios (LPR), a common marker of ischemia, were unchanged. CONCLUSIONS: This study reports that elevated levels of glutamate are found in the perihematomal region after ICH and are decreased during hematoma drainage. Conversely, ischemic LPRs are not found in perihematomal regions and were unchanged during hematoma drainage. These data suggest that excitotoxicity related to glutamate may have an important impact on secondary injury. The data failed to support the role of ischemia in secondary perihematomal damage. PMID- 17356189 TI - The treatment of spinal cord ischemia following thoracic endovascular aortic repair. AB - INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) is a promising alternative to the traditional open surgical approach, though spinal cord ischemia remains a challenging complication. Spinal cord ischemia has been treated using lumbar cerebral spinal fluid (CSF) drainage. METHODS: We report a case of delayed spinal cord ischemia that was successfully treated with vasopressor therapy alone, supporting aggressive blood pressure augmentation as a primary intervention to increase spinal cord perfusion. RESULTS: The pathophysiology of spinal cord ischemia after TEVAR is presented along with our treatment protocol. PMID- 17356190 TI - Perfusion CT to evaluate the effect of transluminal angioplasty on cerebral perfusion in the treatment of vasospasm after subarachnoid hemorrhage. AB - INTRODUCTION: Delayed ischemic neurologic deficits secondary to vasospasm are a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Treatment of vasospasm after SAH is associated with complications, and reliable techniques for evaluating effects of treatment of vasospasm in such patients are warranted. We present the use of perfusion computed tomography (PTC) to evaluate the effect of transluminal percutaneous angioplasty in a with SAH and vasospasm induced ischemia. METHODS: Dynamic PCT with deconvolution produced maps of time to-peak, mean transit time, regional cerebral blood flow, and regional cerebral blood volume, with a computerized automated map of the infarct and penumbra. CT scanners with quadruple detector array were used before and after angioplasty. RESULTS: Before angioplasty and intraarterial papaverine, PCT showed normal to decreased cerebral blood flow and increased cerebral blood volume and mean transit time in the middle cerebral artery territory of the left hemisphere. After angioplasty and intraarterial papaverine, PCT showed normalization of perfusion parameters. CONCLUSION: PCT can be a useful technique in monitoring angioplasty treatment effects in patients with vasospasm after SAH. PMID- 17356191 TI - Selective abolition of the vestibular-ocular reflex by sedative drugs. AB - INTRODUCTION: The vestibulo-ocular reflex (VOR) is an important part of the neurological examination of the patient with coma when determining brainstem function. VOR is tested via the oculocephalic reflex (OCR) and the oculovestibular reflex (OVR), or cold calorics. It has been noted that sedative medications, such as opioids and benzodiazepines, can diminish or abolish the VOR. METHODS: We performed a chart review on three patients noted to have absent VOR at initial neurological assessment as an isolated finding. RESULTS: The three patients ranged in age from 45-74 years. Two patients presented with intentional drug overdoses, whereas the third patient had a complicated course postcardiac surgery and received sedative drugs. All three patients initially had absent responses to OCR and cold calorics bilaterally. However, all other brainstem functions were normal at the initial examination. All three patients regained both OCR and OVR within 24 hours after sedative medication had been removed. CONCLUSION: Sedatives may selectively and transiently abolish the VOR, altering the clinical examination; this is to be considered in the examination of a patient with coma. PMID- 17356192 TI - Decompressive bifrontal craniectomy for malignant intracranial pressure following anterior communicating artery aneurysm rupture: two case reports. AB - There are a number of causes of raised intracranial pressure (ICP) following aneurysm rupture. These include primary and diffuse hypoxic brain injury, intracranial hematomas, cerebral ischemia or infarction, and obstructive hydrocephalus. More localized brain swelling can also occur: the result of vasogenic and cytotoxic edema resulting from overlying bleeding in the subarachnoid spaces. In the case of rupture of an anterior communicating artery (ACommA) aneurysm and interhemispheric subarachnoid hemorrhage (SAH), this swelling can occur in both frontal lobes and when extensive, and the resulting intracranial hypertension can be difficult to manage with ventricular drainage and medical treatment. We describe two patients in whom decompressive bifrontal craniectomy was associated with successful ICP management and good clinical outcomes. PMID- 17356193 TI - The CT pattern of a ruptured P3 posterior cerebral artery aneurysm. AB - A 48-year-old male smoker with a history of significant alcohol use developed thunderclap headache during sexual intercourse. On neurological exam, he was confused and agitated with a Glasgow Coma Score of 11 (E3, M6, V2). Computed tomography (CT) of the brain revealed diffuse subarachnoid hemorrhage (SAH) with blood notably present in the quadrigeminal and supracerebellar cisterns (Figure 1). Cerebral angiogram demonstrated a distal P3 posterior cerebral artery (PCA) aneurysm (Figure 2). The PCA aneurysm was successfully treated with endovascular coil occlusion. PMID- 17356194 TI - Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): rationale and design. AB - This trial is a multicenter open-labeled pilot trial to determine the tolerability and safety of three escalating levels of antihypertensive treatment goals for acute hypertension in 60 subjects with supratentorial intracerebral hemorrhage (ICH). The pilot trial is the natural development of numerous case series evaluating the effect of antihypertensive treatment of acute hypertension in subjects with ICH. The proposed trial will have important public health implications by providing necessary information for a definitive phase III study regarding the efficacy of antihypertensive treatment of acute hypertension in subjects with ICH. The specific aims of the present pilot study are to: (1) Determine the tolerability of the treatment as assessed by achieving and maintaining three different systolic blood pressure goals with intravenous nicardipine infusion for 18 to 24 hours postictus in subjects with ICH who present within 6 hours of symptom onset; (2) Define the safety, assessed by the rate of neurological deterioration during treatment and serious adverse events, of three escalating systolic blood pressure treatment goals using intravenous nicardipine infusion; and (3) Obtain preliminary estimates of the treatment effect using the rate of hematoma expansion (within 24 hours) and modified Rankin scale and Barthel index at 3 months following symptom onset. PMID- 17356195 TI - H2O coma. AB - INTRODUCTION: Water intoxication is a rare cause of coma. The leading causes of excessive hydration are endurance exercise, drug abuse, iatrogenic, cerebral salt wasting, or psychiatric conditions. Self-induced water intoxication in an otherwise healthy person is exceedingly rare. METHODS: Single patient case report and review of the literature. RESULTS: We describe a previously fit and healthy 13-year-old girl who was admitted to the Accident and Emergency department in a comatose state following an unwitnessed seizure. On examination she had a fluctuating Glasgow Coma Score, bilateral mydriatic pupils that responded poorly to light, and an upgoing right plantar. Blood pressure, pulse rate, and oximetry, as well as body mass index, were normal. Routine blood examination revealed hyponatremia, hypochloremia, and a low hematocrit. Water intoxication was suspected and confirmed by reduced urine sodium, serum, and urine osmolality. The computed tomographic brain scan, lumbar puncture opening pressure, and cerebrospinal fluid examination were all normal. She regained consciousness and was fully orientated within 24 hours following intravenous NaCl administration. In this case, thirst without any other apparent pathology led to voluntary water intoxication. CONCLUSIONS: Our case illustrates the classic picture of self induced water intoxication in a previously fit and healthy patient. PMID- 17356196 TI - Cerebral correlates of hyponatremia. AB - Hyponatremia, defined as a serum sodium concentration ([Na+]) less than 135 mEq/L, is commonly caused by elevated levels of the hormone arginine vasopressin (AVP), which causes water retention. The principal organ affected by disease related morbidity is the brain. The neurologic complications associated with hyponatremia are attributable to cerebral edema and increased intracranial pressure, caused by the osmotically driven movement of water from the extracellular compartment into brain cells. Although neurologic symptoms induced by hyponatremia are limited by an adaptive brain mechanism known as "regulatory volume decrease," an overly rapid correction of serum [Na+] before the reversal of this adaptive response can also produce neurologic damage. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a frequent cause of hyponatremia related to central nervous system disorders, neurosurgery, or the use of psychoactive drugs. Fluid restriction is the standard of care for patients with SIADH who are asymptomatic or who have only mild symptoms, but patients with severe or symptomatic hyponatremia require more aggressive therapy. Infusion of hypertonic saline is the usual approach to the treatment of symptomatic hyponatremia, but patients require frequent monitoring. Pharmacologic agents such as demeclocycline and lithium may be effective in some patients but are associated with undesirable adverse events. The AVPreceptor antagonists are a new therapeutic class for the treatment of hyponatremia. The first agent in this class approved for the treatment of euvolemic hyponatremia in hospitalized patients is conivaptan. Two other agents, tolvaptan and lixivaptan, are being evaluated in patients with euvolemic and hypervolemic hyponatremia. The AVP receptor antagonists block the effects of elevated AVP and promote aquaresis, the electrolyte-sparing excretion of water, resulting in the correction of serum [Na+]. These agents may also have intrinsic neuroprotective effects. PMID- 17356197 TI - Analyzing image structure by multidimensional frequency modulation. AB - We develop a mathematical framework for quantifying and understanding multidimensional frequency modulations in digital images. We begin with the widely accepted definition of the instantaneous frequency vector (IF) as the gradient of the phase and define the instantaneous frequency gradient tensor (IFGT) as the tensor of component derivatives of the IF vector. Frequency modulation bounds are derived and interpreted in terms of the eigendecomposition of the IFGT. Using the IFGT, we derive the ordinary differential equations (ODEs) that describe image flowlines. We study the diagonalization of the ODEs of multidimensional frequency modulation on the IFGT eigenvector coordinate system and suggest that separable transforms can be computed along these coordinates. We illustrate these new methods of image pattern analysis on textured and fingerprint images. We envision that this work will find value in applications involving the analysis of image textures that are nonstationary yet exhibit local regularity. Examples of such textures abound in nature. PMID- 17356198 TI - Gaussian mean-shift is an EM algorithm. AB - The mean-shift algorithm, based on ideas proposed by Fukunaga and Hostetler [16], is a hill-climbing algorithm on the density defined by a finite mixture or a kernel density estimate. Mean-shift can be used as a nonparametric clustering method and has attracted recent attention in computer vision applications such as image segmentation or tracking. We show that, when the kernel is Gaussian, mean shift is an expectation-maximization (EM) algorithm and, when the kernel is non Gaussian, mean-shift is a generalized EM algorithm. This implies that mean-shift converges from almost any starting point and that, in general, its convergence is of linear order. For Gaussian mean-shift, we show: 1) the rate of linear convergence approaches 0 (superlinear convergence) for very narrow or very wide kernels, but is often close to 1 (thus, extremely slow) for intermediate widths and exactly 1 (sublinear convergence) for widths at which modes merge, 2) the iterates approach the mode along the local principal component of the data points from the inside of the convex hull of the data points, and 3) the convergence domains are nonconvex and can be disconnected and show fractal behavior. We suggest ways of accelerating mean-shift based on the EM interpretation. PMID- 17356199 TI - A lattice-based MRF model for dynamic near-regular texture tracking. AB - A near-regular texture (NRT) is a geometric and photometric deformation from its regular origin--a congruent wallpaper pattern formed by 2D translations of a single tile. A dynamic NRT is an NRT under motion. Although NRTs are pervasive in man-made and natural environments, effective computational algorithms for NRTs are few. This paper addresses specific computational challenges in modeling and tracking dynamic NRTs, including ambiguous correspondences, occlusions, and drastic illumination and appearance variations. We propose a lattice-based Markov Random-Field (MRF) model for dynamic NRTs in a 3D spatiotemporal space. Our model consists of a global lattice structure that characterizes the topological constraint among multiple textons and an image observation model that handles local geometry and appearance variations. Based on the proposed MRF model, we develop a tracking algorithm that utilizes belief propagation and particle filtering to effectively handle the special challenges of the dynamic NRT tracking without any assumption on the motion types or lighting conditions. We provide quantitative evaluations of the proposed method against existing tracking algorithms and demonstrate its applications in video editing. PMID- 17356200 TI - Integrating motion, illumination, and structure in video sequences with applications in illumination-invariant tracking. AB - In this paper, we present a theory for combining the effects of motion, illumination, 3D structure, albedo, and camera parameters in a sequence of images obtained by a perspective camera. We show that the set of all Lambertian reflectance functions of a moving object, at any position, illuminated by arbitrarily distant light sources, lies "close" to a bilinear subspace consisting of nine illumination variables and six motion variables. This result implies that, given an arbitrary video sequence, it is possible to recover the 3D structure, motion, and illumination conditions simultaneously using the bilinear subspace formulation. The derivation builds upon existing work on linear subspace representations of reflectance by generalizing it to moving objects. Lighting can change slowly or suddenly, locally or globally, and can originate from a combination of point and extended sources. We experimentally compare the results of our theory with ground truth data and also provide results on real data by using video sequences of a 3D face and the entire human body with various combinations of motion and illumination directions. We also show results of our theory in estimating 3D motion and illumination model parameters from a video sequence. PMID- 17356201 TI - The asymmetry of image registration and its application to face tracking. AB - Most image registration problems are formulated in an asymmetric fashion. Given a pair of images, one is implicitly or explicitly regarded as a template and warped onto the other to match as well as possible. In this paper, we focus on this seemingly arbitrary choice of the roles and reveal how it may lead to biased warp estimates in the presence of relative scaling. We present a principled way of selecting the template and explain why only the correct asymmetric form, with the potential inclusion of a blurring step, can yield an unbiased estimator. We validate our analysis in the domain of model-based face tracking. We show how the usual Active Appearance Model (AAM) formulation overlooks the asymmetry issue, causing the fitting accuracy to degrade quickly when the observed objects are smaller than their model. We formulate a novel, "resolution-aware fitting" (RAF) algorithm that respects the asymmetry and incorporates an explicit model of the blur caused by the camera's sensing elements into the fitting formulation. We compare the RAF algorithm against a state-of-the-art tracker across a variety of resolutions and AAM complexity levels. Experimental results show that RAF significantly improves the estimation accuracy of both shape and appearance parameters when fitting to low-resolution data. Recognizing and accounting for the asymmetry of image registration leads to tangible accuracy improvements in analyzing low-resolution imagery. PMID- 17356202 TI - Robust object matching for persistent tracking with heterogeneous features. AB - This paper addresses the problem of matching vehicles across multiple sightings under variations in illumination and camera poses. Since multiple observations of a vehicle are separated in large temporal and/or spatial gaps, thus prohibiting the use of standard frame-to-frame data association, we employ features extracted over a sequence during one time interval as a vehicle fingerprint that is used to compute the likelihood that two or more sequence observations are from the same or different vehicles. Furthermore, since our domain is aerial video tracking, in order to deal with poor image quality and large resolution and quality variations, our approach employs robust alignment and match measures for different stages of vehicle matching. Most notably, we employ a heterogeneous collection of features such as lines, points, and regions in an integrated matching framework. Heterogeneous features are shown to be important. Line and point features provide accurate localization and are employed for robust alignment across disparate views. The challenges of change in pose, aspect, and appearances across two disparate observations are handled by combining a novel feature-based quasi-rigid alignment with flexible matching between two or more sequences. However, since lines and points are relatively sparse, they are not adequate to delineate the object and provide a comprehensive matching set that covers the complete object. Region features provide a high degree of coverage and are employed for continuous frames to provide a delineation of the vehicle region for subsequent generation of a match measure. Our approach reliably delineates objects by representing regions as robust blob features and matching multiple regions to multiple regions using Earth Mover's Distance (EMD). Extensive experimentation under a variety of real-world scenarios and over hundreds of thousands of Confirmatory Identification (CID) trails has demonstrated about 95 percent accuracy in vehicle reacquisition with both visible and Infrared (IR) imaging cameras. PMID- 17356203 TI - An efficient Earth Mover's Distance algorithm for robust histogram comparison. AB - We propose EMD-L1: a fast and exact algorithm for computing the Earth Mover's Distance (EMD) between a pair of histograms. The efficiency of the new algorithm enables its application to problems that were previously prohibitive due to high time complexities. The proposed EMD-L1 significantly simplifies the original linear programming formulation of EMD. Exploiting the L1 metric structure, the number of unknown variables in EMD-L1 is reduced to O(N) from O(N2) of the original EMD for a histogram with N bins. In addition, the number of constraints is reduced by half and the objective function of the linear program is simplified. Formally, without any approximation, we prove that the EMD-L1 formulation is equivalent to the original EMD with a L1 ground distance. To perform the EMD-L1 computation, we propose an efficient tree-based algorithm, Tree-EMD. Tree-EMD exploits the fact that a basic feasible solution of the simplex algorithm-based solver forms a spanning tree when we interpret EMD-L1 as a network flow optimization problem. We empirically show that this new algorithm has an average time complexity of O(N2), which significantly improves the best reported supercubic complexity of the original EMD. The accuracy of the proposed methods is evaluated by experiments for two computation-intensive problems: shape recognition and interest point matching using multidimensional histogram-based local features. For shape recognition, EMD-L1 is applied to compare shape contexts on the widely tested MPEG7 shape data set, as well as an articulated shape data set. For interest point matching, SIFT, shape context and spin image are tested on both synthetic and real image pairs with large geometrical deformation, illumination change, and heavy intensity noise. The results demonstrate that our EMD-L1-based solutions outperform previously reported state of-the-art features and distance measures in solving the two tasks. PMID- 17356204 TI - Sharing visual features for multiclass and multiview object detection. AB - We consider the problem of detecting a large number of different classes of objects in cluttered scenes. Traditional approaches require applying a battery of different classifiers to the image, at multiple locations and scales. This can be slow and can require a lot of training data since each classifier requires the computation of many different image features. In particular, for independently trained detectors, the (runtime) computational complexity and the (training-time) sample complexity scale linearly with the number of classes to be detected. We present a multitask learning procedure, based on boosted decision stumps, that reduces the computational and sample complexity by finding common features that can be shared across the classes (and/or views). The detectors for each class are trained jointly, rather than independently. For a given performance level, the total number of features required and, therefore, the runtime cost of the classifier, is observed to scale approximately logarithmically with the number of classes. The features selected by joint training are generic edge-like features, whereas the features chosen by training each class separately tend to be more object-specific. The generic features generalize better and considerably reduce the computational cost of multiclass object detection. PMID- 17356205 TI - Photo-consistent reconstruction of semitransparent scenes by density-sheet decomposition. AB - This paper considers the problem of reconstructing visually realistic 3D models of dynamic semitransparent scenes, such as fire, from a very small set of simultaneous views (even two). We show that this problem is equivalent to a severely underconstrained computerized tomography problem, for which traditional methods break down. Our approach is based on the observation that every pair of photographs of a semitransparent scene defines a unique density field, called a Density Sheet, that 1) concentrates all its density on one connected, semitransparent surface, 2) reproduces the two photos exactly, and 3) is the most spatially compact density field that does so. From this observation, we reduce reconstruction to the convex combination of sheet-like density fields, each of which is derived from the Density Sheet of two input views. We have applied this method specifically to the problem of reconstructing 3D models of fire. Experimental results suggest that this method enables high-quality view synthesis without overfitting artifacts. PMID- 17356206 TI - Laplacian operator-based edge detectors. AB - Laplacian operator is a second derivative operator often used in edge detection. Compared with the first derivative-based edge detectors such as Sobel operator, the Laplacian operator may yield better results in edge localization. Unfortunately, the Laplacian operator is very sensitive to noise. In this paper, based on the Laplacian operator, a model is introduced for making some edge detectors. Also, the optimal threshold is introduced for obtaining a Maximum a Posteriori (MAP) estimate of edges. PMID- 17356207 TI - Part-based object retrieval in cluttered environment. AB - A novel local structural approach, which is a sequel to our previous work, is proposed in this paper for object retrieval in a cluttered and occluded environment without identifying the outlines of an object. It works by first extracting consistent and structurally unique local neighborhood from inputs or models and then voting on the optimal matches employing dynamic programming and a novel hypercube-based indexing structure. The proposed concepts have been tested on a database with thousands of images and compared with the six nearest neighbors shape description with superior results. PMID- 17356208 TI - Equivalence of some common linear feature extraction techniques for appearance based object recognition tasks. AB - Recently, a number of empirical studies have compared the performance of PCA and ICA as feature extraction methods in appearance-based object recognition systems, with mixed and seemingly contradictory results. In this paper, we briefly describe the connection between the two methods and argue that whitened PCA may yield identical results to ICA in some cases. Furthermore, we describe the specific situations in which ICA might significantly improve on PCA. PMID- 17356209 TI - Robust pose estimation and recognition using non-gaussian modeling of appearance subspaces. AB - We present an original appearance model that generalizes the usual Gaussian visual subspace model to non-Gaussian and nonparametric distributions. It can be useful for the modeling and recognition of images under difficult conditions such as large occlusions and cluttered backgrounds. Inference under the model is efficiently solved using the mean shift algorithm. PMID- 17356210 TI - Demand characteristics in assessing motion sickness in a virtual environment: or does taking a motion sickness questionnaire make you sick? AB - The experience of motion sickness in a virtual environment may be measured through pre and postexperiment self-reported questionnaires such as the Simulator Sickness Questionnaire (SSQ). Although research provides converging evidence that users of virtual environments can experience motion sickness, there have been no controlled studies to determine to what extent the user's subjective response is a demand characteristic resulting from pre and posttest measures. In this study, subjects were given either SSQ's both pre and postvirtual environment immersion, or only postimmersion. This technique tested for contrast effects due to demand characteristics in which administration of the questionnaire itself suggested to the participant that the virtual environment may produce motion sickness. Results indicate that reports of motion sickness after immersion in a virtual environment are much greater when both pre and postquestionnaires are given than when only a posttest questionnaire is used. The implications for assessments of motion sickness in virtual environments are discussed. PMID- 17356211 TI - Egocentric depth judgments in optical, see-through augmented reality. AB - Abstract-A fundamental problem in optical, see-through augmented reality (AR) is characterizing how it affects the perception of spatial layout and depth. This problem is important because AR system developers need to both place graphics in arbitrary spatial relationships with real-world objects, and to know that users will perceive them in the same relationships. Furthermore, AR makes possible enhanced perceptual techniques that have no real-world equivalent, such as x-ray vision, where AR users are supposed to perceive graphics as being located behind opaque surfaces. This paper reviews and discusses protocols for measuring egocentric depth judgments in both virtual and augmented environments, and discusses the well-known problem of depth underestimation in virtual environments. It then describes two experiments that measured egocentric depth judgments in AR. Experiment I used a perceptual matching protocol to measure AR depth judgments at medium and far-field distances of 5 to 45 meters. The experiment studied the effects of upper versus lower visual field location, the x ray vision condition, and practice on the task. The experimental findings include evidence for a switch in bias, from underestimating to overestimating the distance of AR-presented graphics, at approximately 23 meters, as well as a quantification of how much more difficult the x-ray vision condition makes the task. Experiment II used blind walking and verbal report protocols to measure AR depth judgments at distances of 3 to 7 meters. The experiment examined real-world objects, real-world objects seen through the AR display, virtual objects, and combined real and virtual objects. The results give evidence that the egocentric depth of AR objects is underestimated at these distances, but to a lesser degree than has previously been found for most virtual reality environments. The results are consistent with previous studies that have implicated a restricted field-of view, combined with an inability for observers to scan the ground plane in a near to-far direction, as explanations for the observed depth underestimation. PMID- 17356212 TI - Comparing interpersonal interactions with a virtual human to those with a real human. AB - This paper provides key insights into the construction and evaluation of interpersonal simulators--systems that enable interpersonal interaction with virtual humans. Using an interpersonal simulator, two studies were conducted that compare interactions with a virtual human to interactions with a similar real human. The specific interpersonal scenario employed was that of a medical interview. Medical students interacted with either a virtual human simulating appendicitis or a real human pretending to have the same symptoms. In Study I (n = 24), medical students elicited the same information from the virtual and real human, indicating that the content of the virtual and real interactions were similar. However, participants appeared less engaged and insincere with the virtual human. These behavioral differences likely stemmed from the virtual human's limited expressive behavior. Study II (n = 58) explored participant behavior using new measures. Nonverbal behavior appeared to communicate lower interest and a poorer attitude toward the virtual human. Some subjective measures of participant behavior yielded contradictory results, highlighting the need for objective, physically-based measures in future studies. PMID- 17356213 TI - A six degree-of-freedom god-object method for haptic display of rigid bodies with surface properties. AB - This paper describes a generalization of the god-object method for haptic interaction between rigid bodies. Our approach separates the computation of the motion of the six degree-of-freedom god-object from the computation of the force applied to the user. The motion of the god-object is computed using continuous collision detection and constraint-based quasi-statics, which enables high quality haptic interaction between contacting rigid bodies. The force applied to the user is computed using a novel constraint-based quasi-static approach, which allows us to suppress force artifacts typically found in previous methods. The constraint-based force applied to the user, which handles any number of simultaneous contact points, is computed within a few microseconds, while the update of the configuration of the rigid god-object is performed within a few milliseconds for rigid bodies containing up to tens of thousands of triangles. Our approach has been successfully tested on complex benchmarks. Our results show that the separation into asynchronous processes allows us to satisfy the different update rates required by the haptic and visual displays. Force shading and textures can be added and enlarge the range of haptic perception of a virtual environment. This paper is an extension of [1]. PMID- 17356214 TI - Deformable model retrieval based on topological and geometric signatures. AB - With the increasing popularity of 3D applications such as computer games, a lot of 3D geometry models are being created. To encourage sharing and reuse, techniques that support matching and retrieval of these models are emerging. However, only a few of them can handle deformable models, that is, models of different poses, and these methods are generally very slow. In this paper, we present a novel method for efficient matching and retrieval of 3D deformable models. Our research idea stresses using both topological and geometric features at the same time. First, we propose Topological Point Ring (TPR) analysis to locate reliable topological points and rings. Second, we capture both local and global geometric information to characterize each of these topological features. To compare the similarity of two models, we adapt the Earth Mover Distance (EMD) as the distance function and construct an indexing tree to accelerate the retrieval process. We demonstrate the performance of the new method, both in terms of accuracy and speed, through a large number of experiments. PMID- 17356215 TI - Comparison of four freely available frameworks for image processing and visualization that use ITK. AB - Most image processing and visualization applications allow users to configure computation parameters and manipulate the resulting visualizations. SCIRun, VolView, MeVisLab, and the Medical Interaction Toolkit (MITK) are four image processing and visualization frameworks that were built for these purposes. All frameworks are freely available and all allow the use of the ITK C++ library. In this paper, the benefits and limitations of each visualization framework are presented to aid both application developers and users in the decision of which framework may be best to use for their application. The analysis is based on more than 50 evaluation criteria, functionalities, and example applications. We report implementation times for various steps in the creation of a reference application in each of the compared frameworks. The data-flow programming frameworks, SCIRun and MeVisLab, were determined to be best for developing application prototypes, while VolView was advantageous for nonautomatic end-user applications based on existing ITK functionalities, and MITK was preferable for automated end-user applications that might include new ITK classes specifically designed for the application. PMID- 17356216 TI - Value and relation display: interactive visual exploration of large data sets with hundreds of dimensions. AB - Few existing visualization systems can handle large data sets with hundreds of dimensions, since high-dimensional data sets cause clutter on the display and large response time in interactive exploration. In this paper, we present a significantly improved multidimensional visualization approach named Value and Relation (VaR) display that allows users to effectively and efficiently explore large data sets with several hundred dimensions. In the VaR display, data values and dimension relationships are explicitly visualized in the same display by using dimension glyphs to explicitly represent values in dimensions and glyph layout to explicitly convey dimension relationships. In particular, pixel oriented techniques and density-based scatterplots are used to create dimension glyphs to convey values. Multidimensional scaling, Jigsaw map hierarchy visualization techniques, and an animation metaphor named Rainfall are used to convey relationships among dimensions. A rich set of interaction tools has been provided to allow users to interactively detect patterns of interest in the VaR display. A prototype of the VaR display has been fully implemented. The case studies presented in this paper show how the prototype supports interactive exploration of data sets of several hundred dimensions. A user study evaluating the prototype is also reported in this paper. PMID- 17356217 TI - Shadow elimination and blinding light suppression for interactive projected displays. AB - A major problem with interactive displays based on front projection is that users cast undesirable shadows on the display surface. This paper demonstrates that shadows can be muted by redundantly illuminating the display surface using multiple projectors, all mounted at different locations. However, this technique alone does not eliminate shadows: Multiple projectors create multiple dark regions on the surface (penumbral occlusions) and cast undesirable light onto the users. These problems can be solved by eliminating shadows and suppressing the light that falls on occluding users by actively modifying the projected output. This paper categorizes various methods that can be used to achieve redundant illumination, shadow elimination, and blinding light suppression and evaluates their performance. PMID- 17356218 TI - Efficient collision detection within deforming spherical sliding contact. AB - Handling the evolving permanent contact of deformable objects leads to a collision detection problem of high computing cost. Situations in which this type of contact happens are becoming more and more present with the increasing complexity of virtual human models, especially for the emerging medical applications. In this context, we propose a novel collision detection approach to deal with situations in which soft structures are in constant but dynamic contact, which is typical of 3D biological elements. Our method proceeds in two stages: First, in a preprocessing stage, a mesh is chosen under certain conditions as a reference mesh and is spherically sampled. In the collision detection stage, the resulting table is exploited for each vertex of the other mesh to obtain, in constant time, its signed distance to the fixed mesh. The two working hypotheses for this approach to succeed are typical of the deforming anatomical systems we target: First, the two meshes retain a layered configuration with respect to a central point and, second, the fixed mesh tangential deformation is bounded by the spherical sampling resolution. Within this context, the proposed approach can handle large relative displacements, reorientations, and deformations of the mobile mesh. We illustrate our method in comparison with other techniques on a biomechanical model of the human hip joint. PMID- 17356219 TI - Curve-skeleton properties, applications, and algorithms. AB - Curve-skeletons are thinned 1D representations of 3D objects useful for many visualization tasks including virtual navigation, reduced-model formulation, visualization improvement, animation, etc. There are many algorithms in the literature describing extraction methodologies for different applications; however, it is unclear how general and robust they are. In this paper, we provide an overview of many curve-skeleton applications and compile a set of desired properties of such representations. We also give a taxonomy of methods and analyze the advantages and drawbacks of each class of algorithms. PMID- 17356220 TI - Free-form geometric modeling by integrating parametric and implicit PDEs. AB - Parametric PDE techniques, which use partial differential equations (PDEs) defined over a 2D or 3D parametric domain to model graphical objects and processes, can unify geometric attributes and functional constraints of the models. PDEs can also model implicit shapes defined by level sets of scalar intensity fields. In this paper, we present an approach that integrates parametric and implicit trivariate PDEs to define geometric solid models containing both geometric information and intensity distribution subject to flexible boundary conditions. The integrated formulation of second-order or fourth-order elliptic PDEs permits designers to manipulate PDE objects of complex geometry and/or arbitrary topology through direct sculpting and free-form modeling. We developed a PDE-based geometric modeling system for shape design and manipulation of PDE objects. The integration of implicit PDEs with parametric geometry offers more general and arbitrary shape blending and free-form modeling for objects with intensity attributes than pure geometric models. PMID- 17356221 TI - High resolution animated scenes from stills. AB - Current techniques for generating animated scenes involve either videos (whose resolution is limited) or a single image (which requires a significant amount of user interaction). In this paper, we describe a system that allows the user to quickly and easily produce a compelling-looking animation from a small collection of high resolution stills. Our system has two unique features. First, it applies an automatic partial temporal order recovery algorithm to the stills in order to approximate the original scene dynamics. The output sequence is subsequently extracted using a second-order Markov Chain model. Second, a region with large motion variation can be automatically decomposed into semiautonomous regions such that their temporal orderings are softly constrained. This is to ensure motion smoothness throughout the original region. The final animation is obtained by frame interpolation and feathering. Our system also provides a simple-to-use interface to help the user to fine-tune the motion of the animated scene. Using our system, an animated scene can be generated in minutes. We show results for a variety of scenes. PMID- 17356222 TI - Texture-based visualization of unsteady 3D flow by real-time advection and volumetric illumination. AB - This paper presents an interactive technique for the dense texture-based visualization of unsteady 3D flow, taking into account issues of computational efficiency and visual perception. High efficiency is achieved by a 3D graphics processing unit (GPU)-based texture advection mechanism that implements logical 3D grid structures by physical memory in the form of 2D textures. This approach results in fast read and write access to physical memory, independent of GPU architecture. Slice-based direct volume rendering is used for the final display. We investigate two alternative methods for the volumetric illumination of the result of texture advection: First, gradient-based illumination that employs a real-time computation of gradients, and, second, line-based lighting based on illumination in codimension 2. In addition to the Phong model, perception-guided rendering methods are considered, such as cool/warm shading, halo rendering, or color-based depth cueing. The problems of clutter and occlusion are addressed by supporting a volumetric importance function that enhances features of the flow and reduces visual complexity in less interesting regions. GPU implementation aspects, performance measurements, and a discussion of results are included to demonstrate our visualization approach. PMID- 17356223 TI - A radial adaptation of the Sugiyama framework for visualizing hierarchical information. AB - In radial drawings of hierarchical graphs, the vertices are placed on concentric circles rather than on horizontal lines and the edges are drawn as outward monotone segments of spirals rather than straight lines as it is done in the standard Sugiyama framework. This drawing style is well suited for the visualization of centrality in social networks and similar concepts. Radial drawings also allow a more flexible edge routing than horizontal drawings, as edges can be routed around the center in two directions. In experimental results, this reduces the number of crossings by approximately 30 percent on average. Few crossings are one of the major criteria for human readability. This paper is a detailed description of a complete framework for visualizing hierarchical information in a new radial fashion. Particularly, we briefly cover extensions of the level assignment step to benefit from the increasing perimeters of the circles, present three heuristics for crossing reduction in radial level drawings, and also show how to visualize the results. PMID- 17356224 TI - Time-varying BRDFs. AB - The properties of virtually all real-world materials change with time, causing their bidirectional reflectance distribution functions (BRDFs) to be time varying. However, none of the existing BRDF models and databases take time variation into consideration; they represent the appearance of a material at a single time instance. In this paper, we address the acquisition, analysis, modeling, and rendering of a wide range of time-varying BRDFs (TVBRDFs). We have developed an acquisition system that is capable of sampling a material's BRDF at multiple time instances, with each time sample acquired within 36 sec. We have used this acquisition system to measure the BRDFs of a wide range of time-varying phenomena, which include the drying of various types of paints (watercolor, spray, and oil), the drying of wet rough surfaces (cement, plaster, and fabrics), the accumulation of dusts (household and joint compound) on surfaces, and the melting of materials (chocolate). Analytic BRDF functions are fit to these measurements and the model parameters' variations with time are analyzed. Each category exhibits interesting and sometimes nonintuitive parameter trends. These parameter trends are then used to develop analytic TVBRDF models. The analytic TVBRDF models enable us to apply effects such as paint drying and dust accumulation to arbitrary surfaces and novel materials. PMID- 17356225 TI - Manifold dual contouring. AB - Dual Contouring (DC) is a feature-preserving isosurfacing method that extracts crack-free surfaces from both uniform and adaptive octree grids. We present an extension of DC that further guarantees that the mesh generated is a manifold even under adaptive simplification. Our main contribution is an octree-based topology-preserving vertex-clustering algorithm for adaptive contouring. The contoured surface generated by our method contains only manifold vertices and edges, preserves sharp features, and possesses much better adaptivity than those generated by other isosurfacing methods under topologically safe simplification. PMID- 17356226 TI - Physics-based subsurface visualization of human tissue. AB - In this paper, we present a framework for simulating light transport in three dimensional tissue with inhomogeneous scattering properties. Our approach employs a computational model to simulate light scattering in tissue through the finite element solution of the diffusion equation. Although our model handles both visible and nonvisible wavelengths, we especially focus on the interaction of near infrared (NIR) light with tissue. Since most human tissue is permeable to NIR light, tools to noninvasively image tumors, blood vasculature, and monitor blood oxygenation levels are being constructed. We apply this model to a numerical phantom to visually reproduce the images generated by these real-world tools. Therefore, in addition to enabling inverse design of detector instruments, our computational tools produce physically-accurate visualizations of subsurface structures. PMID- 17356227 TI - Image-based streamline generation and rendering. AB - Seeding streamlines in 3D flow fields without considering their projections in screen space can produce visually cluttered rendering results. Streamlines will overlap or intersect with each other in the output image, which makes it difficult for the user to perceive the underlying flow structure. This paper presents a method to control the seeding and generation of streamlines in image space to avoid visual cluttering and allow a more flexible exploration of flow fields. In our algorithm, 2D images with depth maps generated by a variety of visualization techniques can be used as input from which seeds are placed and streamlines are generated. The density and rendering styles of streamlines can be flexibly controlled based on various criteria to improve visual clarity. With our image space approach, it is straightforward to implement the level of detail rendering, depth peeling, and stylized rendering of streamlines to allow for more effective visualization of 3D flow fields. PMID- 17356228 TI - Role of dihydroxyvitamin D(3) and its nuclear receptor in novel directed therapies for cancer. AB - Dihydroxyvitamin D(3) is known to affect broad spectrum of various biochemical and molecular biological reactions in organisms. Research on the role and function of nuclear vitamin D(3) receptors (VDR) playing a role as dihydroxyvitamin D(3) inducible transcription factor belongs to dynamically developing branches of molecular endocrinology. In higher organisms, full functionality of VDR in the form of heterodimer with nuclear 9-cis retinoic acid receptor is essential for biological effects of dihydroxyvitamin D(3). This article summarizes selected effects of biologically active vitamin D(3) acting through their cognate nuclear receptors, and also its potential use in therapy and prevention of various types of cancer. PMID- 17356229 TI - Gene expression of the phenylethanolamine N-methyltransferase is differently modulated in cardiac atria and ventricles. AB - Phenylethanolamine N-methyltransferase (PNMT) is a final enzyme in catecholamine synthesizing cascade that converts noradrenaline to adrenaline. Although most profuse in adrenal medulla, PNMT is expressed also in the heart, particularly in cardiac atria and ventricles. In atria, the PNMT mRNA is much more abundant compared to ventricles. In present study we aimed to find out whether there is a difference in modulation of the PNMT gene expression in cardiac atria and ventricles. We used three methodological approaches: cold as a model of mild stress, hypoxia as a model of cardiac ischemic injury, and transgenic rats (TGR) with incorporated mouse renin gene (mREN-2)27, to determine involvement of renin angiotensin pathway in the PNMT gene expression. We have found that PNMT gene expression was modulated differently in cardiac atria and ventricles. In atria, PNMT mRNA levels were increased by hypoxia, while cold stress decreased PNMT mRNA levels. In ventricles, no significant changes were observed by cold or hypoxia. On the other hand, angiotensin II elevated PNMT gene expression in ventricles, but not in atria. These results suggest that PNMT gene expression is modulated differently in cardiac atria and ventricles and might result in different physiological consequences. PMID- 17356230 TI - Inhibitory effect of C-type natriuretic peptide on L-type calcium channel currents in gastric antral myocytes of guinea pigs. AB - The role of C-type natriuretic peptide (CNP) in the gastrointestinal tract is still unclear. This study was designed to investigate the effect of CNP on barium current (I(Ba)) through the L-type calcium channel in gastric antral myocytes of guinea pigs. The whole-cell patch clamp technique was performed in gastric antral myocytes isolated by collagenase in guinea pigs. CNP significantly inhibited I(Ba) in a dose-dependent manner at the concentrations of 0.001, 0.01, and 0.1 micromol/l, CNP inhibited I(Ba) to 81.56 +/- 2.48 %, 73.64 +/- 3.65 %, and 57.77 +/- 4.93 % of control at 0 mV, respectively. The values of steady-state half inactivation voltage (33.6 +/- 2.6 mV and 33.8 +/- 3.4 mV, in control and CNP groups, respectively) or the half-activation voltage (-12.6 +/- 2.2 mV and 12.4 +/- 1.8 mV) of I(Ba) were not significantly changed (p > 0.05, n = 6). 8-br-cGMP (1 mmol/l) mimicked the effect of CNP on I(Ba), and the peak current of I(Ba) was inhibited from -403.84 +/- 61.87 pA to 318.94 +/- 67.17 pA (p < 0.05, n = 5). In the presence of LY83583 (0.1 micromol/l), a nonspecific inhibitor of guanylate cyclase, CNP (0.1 micromol/l)-induced inhibition of I(Ba) was partially blocked (n = 13, p < 0.05 ). However, when the cell was pretreated with zaprinast (0.1 micromol/l), an inhibitor of cyclic guanosine monophosphate (cGMP) sensitive phosphoesterase, the inhibitory effect of CNP on I(Ba) was significantly potentiated (n = 11, p < 0.05). KT5823 (1 micromol/l), a cGMP-dependent protein kinase (PKG) inhibitor, almost completely blocked CNP-induced inhibition of I(Ba). The results suggested that CNP can inhibit L-type calcium channel currents, and the inhibitory effect is mediated by pGC-cGMP-PKG-dependent signal pathway in gastric antral myocytes of guinea pigs. PMID- 17356231 TI - The combined effect of pycnogenol with ascorbic acid and trolox on the oxidation of lipids and proteins. AB - Pycnogenol (PYC), a procyanidin-rich extract of French maritime pine bark (Pinus pinaster) has strong antioxidant potential and promotes cellular health. The aim of this study was to investigate a possible cooperation of natural antioxidant PYC with synthetic antioxidants ascorbic acid and trolox in the model system of lipid peroxidation determined as conjugated dienes formation in liposomes and on the oxidation of proteins (in BSA and plasma proteins) determined as protein carbonyls. The present study shows that PYC and trolox significantly increased inhibition of lipid peroxidation initiated by copper acetate and tert butylhydroperoxide in concentration and time dependence compared with untreated unilamellar liposomes. PYC and trolox added simultaneously to the oxidized liposomes exerted an additive preventive effect. PYC s inhibitory effect on formation of carbonyl compounds in BSA and plasma proteins, oxidized by two oxidative systems--H2O2/FeSO4 and HOCl, were studied in co-operation with other synthetic antioxidants--ascorbic acid and trolox. We found the synergistic or additive effect of PYC with mentioned antioxidants. PMID- 17356232 TI - Functional remodeling of heart mitochondria in acute diabetes: interrelationships between damage, endogenous protection and adaptation. AB - Rats with streptozotocin-diabetes develop mechanisms of endogenous protection (MEP) that participate actively in functional remodeling of cardiac sarcolemma. Remodeling of sarcolemma is a sign of damage but it also protects the cells of the diabetic heart (DH) against additional energy disbalance due to excessive Ca(2+) entry. Since yet, cardiac mitochondria (MIT) were investigated predominantly from the aspect of damage only. Aims of the present study were: i) to distinguish between acute diabetes-induced changes in function of rat heart MIT which clearly belong to damage from those that reflect the MEP and participate in functional remodeling of the MIT; ii) elucidate the significance of MEP-induced changes in heart MIT for cardiac energetics. Acute diabetes (8 days) was induced in adult male Wistar rats by streptozotocin (STZ, 65 mg.kg(-1) i.p., single dose). On the day 8 after STZ administration, the diabetic animals exhibited 300-330 % increase in blood glucose, triacylglycerols and cholesterol as well as 89.6 % increase in glycohemoglobin (all p < 0.01). The blood level of insulin dropped by 53 % (p < 0.02). State 3 and state 4 oxygen consumptions of DH MIT were decreased against the controls, leading to drop of the respiratory control index (17.9 and 7.3 %) and oxidative phosphorylation rate (OPR, 27.5 and 24.6 %; all p < 0.003-0.02). These effects of damage yielding in strained energy balance of the acute DH were partially alleviated by MEP. The latter involved temporary preservation of the ADP : O ratio, with participation of elevated MIT Mg(2+)-ATPase activity as well as increased formation of MIT substrate and energy transition pores (both p < 0.05). Hence, the energy disbalance of the acute DH was finally manifested in 13 % loss in its AMP content only (p < 0.05). Results indicate that MIT in STZ-DH are functionally remodeled. Defective O2 consumption by MIT renders molecular changes suggestive of a mild hypoxic state but an increase in Mg(2+)-ATPase activity and facilitated energy delivery from MIT to the cytoplasm indicate the presence of MEP acting in the MIT and alleviating the effect of decreased oxidative energy production in the acute DH. PMID- 17356233 TI - In vitro inhibition of lens aldose reductase by (2-benzyl-2,3,4,5-tetrahydro-1H pyrido[4,3-b]indole-8-yl)-acetic acid in enzyme preparations isolated from diabetic rats. AB - (2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-yl)-acetic acid (compound 1), a novel aldose reductase inhibitor, was assayed for efficacy and selectivity to inhibit rat lens aldose reductase under in vitro conditions by using enzyme preparations obtained from diabetic animals. The inhibitory efficiency was characterized by IC(50) in micromolar region. Enzyme kinetics analysis revealed uncompetitive type of inhibition, both in relation to the D,L-glyceraldehyde substrate and to the NADPH cofactor. In testing for selectivity, comparisons to rat kidney aldehyde reductase, an enzyme with the highest homology to aldose reductase, was used. The inhibition selectivity of the compound tested was characterized by selectivity factor around 20 and was even slightly improved under conditions of prolonged experimental diabetes. These findings were identical with those in the control rats. To conclude, the inhibitory mode, efficacy and selectivity of compound 1, a novel aldose reductase inhibitor, was preserved even under the conditions of prolonged STZ-induced experimental diabetes of rats. PMID- 17356234 TI - Structural differences between sensitive and resistant L1210 cells. AB - The main structural differences between sensitive L1210 mouse leukaemic cells and their multidrug resistant counterpart, obtained by adaptation of the parental cell line to vincristine (VCR), concern the size and shape of the cells, their surface properties and changes in organelles involved in proteosynthesis and transport of substances. The resistant cells are larger with higher density of microvilli. In light and electron micrographs containing a group of cells, cells were found to be closer to each other in L1210/VCR cells than in L1210 cells. This difference in cell aggregation suggests different surface properties which could be visualised by decreased staining of L1210/VCR cell surface coat (glycocalyx) with a polycationic dye ruthenium red. A decrease in surface to volume ratio as a consequence of increased cell size in resistant cells is compensated by proliferation of villi and cytoplasmic protrusions of the cell surface. L1210/VCR cells were further distinguished by higher amount of euchromatin, increase in density of rough endoplasmic reticulum, more developed Golgi apparatus and aggregation of free ribosomes into tetrameric and pentameric polyribosomes. These structural changes may be interpreted as a sign of increase in proteosynthesis and transport of substances. PMID- 17356235 TI - Inhibition of (Na(+)/K(+))-ATPase by Cibacron Blue 3G-A and its analogues. AB - A specific feature of anthraquinone dyes (AD) is to mimic the adenine nucleotides ATP, ADP, NAD and NADH, enabling them to act as ligands in interaction with nucleotide-binding sites of several enzymes and receptors. In the present study, the interactions and/or inhibitory effects of eight AD, including Cibacron Blue 3G-A (Reactive Blue 2), Procion Blue MX-R (Reactive Blue 4) and Remazol Brilliant Blue R (Reactive Blue 19) on the activity of (Na(+)/K(+))-ATPase were investigated. The AD used in this paper could be divided into two groups: i) AD1 AD4 that do not contain the triazine moiety; ii) AD5-AD8 that contain the triazine moiety. Interaction affinity between the respective dye and (Na+/K+) ATPase was characterized by means of enzyme kinetics. All AD, excluding AD1 and AD2 (which were practically ineffective) exerted effective competitive inhibition to the (Na(+)/K(+))-ATPase activity. Present study is devoted to elucidation of relationship between the inhibitory efficacy of AD against (Na(+)/K(+))-ATPase activity, their acid-basic properties and their three dimensional structure. From the results obtained, the following conclusions could be driven: 1. Similarities in the mutual position of positively and negatively charged parts of ATP and AD are responsible for their interaction with ATP-binding site of (Na(+)/K(+)) ATPase. This may be documented by fact that mutual position of 1-aminogroup of anthraquinone and -SO3(-) group of benzenesulphonate part of respective AD plays crucial role for inhibition of this enzyme. Distances of these two groups on all effective AD were found to be similar as the distance of the 6-aminogroup of adenine and the second phosphate group on ATP molecule. This similarity could be responsible for biomimetic recognition of AD in ATP-binding loci of (Na(+)/K(+)) ATPase. 2. The affinity of AD to ATP binding site of (Na(+)/K(+))-ATPase increases with increasing values of molar refractivity, i. e., with increasing molecular volume and polarizability. PMID- 17356236 TI - Effect of peroxisome proliferator-activated receptor alpha ligand fenofibrate on K(v) channels in the insulin-secreting cell line HIT-T15. AB - Ligands for peroxisome proliferator-activated receptors alpha (PPARalpha) are clinically used for the treatment of patients with hyperlipidemia. As we have previously shown, a synthetic ligand of PPARalpha, fenofibrate, has a stimulatory effect on insulin secretion in clonal hamster insulinoma beta-cell line HIT-T15 cells. We have also demonstrated that fenofibrate directly inhibits ATP-sensitive potassium (K(ATP)) channels, an effect independent of PPARalpha. In this study, fenofibrate was shown to be able to reduce voltage-dependent K(+) (K(v)) channel currents in voltage-independent manner. Therefore, fenofibrate may modulate insulin secretion not only via inhibition of K(ATP) channels but also via reduction of the K(v) channel current. PMID- 17356237 TI - Medical therapy of malabsorption in patients with head pancreatic resection. PMID- 17356238 TI - Optical coherence tomography for investigation of the pancreatico-biliary system: still experimental? PMID- 17356239 TI - Pancreatic cancer: are we moving forward yet? Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 20th, 2007. AB - Survival for patients with pancreatic cancer remains abysmal. Standard treatment for resected and locally advanced disease usually consists of 5-fluorouracil (5 FU, either bolus or continuous infusion) and external beam radiation. However, recent studies have shown the role of gemcitabine either used alone or incorporated with 5-FU and external beam radiation in this setting. Gemcitabine and erlotinib (Tarceva) are currently the only standard chemotherapeutic agents approved by FDA for the treatment of advanced pancreatic cancer. Combination chemotherapy trials incorporating gemcitabine with other agents such as 5-FU, oxaliplatin, or capecitabine generally show improved outcomes in objective response rates but with little or no improvement in survival in phase III trials. In this article, the author summarizes the key studies in pancreatic cancer presented at the 2007 Gastrointestinal Cancers Symposium (Orlando, FL, USA; January, 2007). The studies discussed here include preliminary results of the Cancer and Leukemia Group B (CALGB) phase III trial of gemcitabine plus bevacizumab and activity of other targeted agents including sorafenib, cetuximab, retrospective and population-based studies evaluating the role of chemo radiotherapy and radiotherapy, an analysis of 3,306 patients from the Surveillance, Epidemiology and End Results (SEER) database evaluating the predictive role of lymph nodes in survival following pancreatectomy and the assessment of novel agents, such as Genexol-PM and S-1. PMID- 17356240 TI - Lung complications in acute pancreatitis. AB - CONTEXT: Severe acute pancreatitis has long been known to be a cause of pulmonary dysfunction and multisystem organ failure. OBJECTIVE: We evaluated the spectrum of pulmonary dysfunction in acute pancreatitis. METHODS: Over a period of one year, 60 patients referred to us with a diagnosis of acute pancreatitis on the basis of clinical findings, CT and elevated serum amylase level were studied prospectively. The computed tomography severe index (CTSI) was used to assess the severity of the pancreatitis. Arterial blood gas analysis and chest X-rays were performed in all patients at admission and at intervals, when clinically indicated. RESULTS: The mean age was 42.9+/-15.9 years (range: 18-80 years) and the etiology of the pancreatitis was gallstones in 29 patients, alcohol in 22 patients while no cause could be ascertained in 9. At presentation to our hospital, 48.3% had mild hypoxemia while 18.3% had moderate to severe hypoxemia (PaO2 less than 60 mmHg). The patients who were hypoxemic at presentation had a higher incidence of organ failure during the course of the disease. Pleural effusion at admission was noticed in 50%, atelectasis in 25%, and pulmonary infiltrates in 6.7%. Respiratory failure developed in 48.3% and the mean+/-SD CTSI in these patients was 8.20+/-2.29. Patients with more than 50% necrosis had more pulmonary dysfunction and needed ventilatory support. The development of consolidation during the course of the disease correlated with the occurrence of respiratory failure (P=0.068) but not with mortality (P=0.193). Similarly, the onset of adult respiratory distress syndrome also correlated with respiratory failure (P<0.001) but, unlike consolidation, adult respiratory distress syndrome correlated with mortality (P<0.001). On logistic regression analysis, the development of respiratory failure and other organ dysfunctions were independent risk factors for mortality. CONCLUSION: Our study on patients who were referred to a tertiary care center points out that hypoxemia at presentation predicts a poor outcome which could be due to the high incidence of associated cardiac and renal failure. At presentation, the presence of pleural effusion but not atelectasis and consolidation correlates with the development of respiratory failure and mortality. Among the respiratory complications developing during the course of acute pancreatitis, consolidation and adult respiratory distress syndrome correlate with respiratory failure while adult respiratory distress syndrome alone leads to poor survival. PMID- 17356241 TI - Pancreatic cross-section: an elliptical model. AB - BACKGROUND: Pancreatic surgery has developed over the last 60 years. A pancreaticoduodenectomy of the pancreatic head and duodenal papilla is the most common procedure. The most popular pancreatic cross-section site of a pancreaticoduodenectomy is the isthmus of the gland. The pancreatic isthmus anatomical configuration is still being considered. STUDY DESIGN: The authors propose a new parametric descriptive system of pancreatic cross-section based on an elliptical model. RESULTS: The pancreatic cross-section was evaluated as a geometric ellipse and the location of the pancreatic duct was based on coordinates. When analyzing the cross-section plane of the pancreatic isthmus, the mean size of the pancreatic isthmus cross-section was 10.46+/-2.34 mm in width (mean+/-SD) and 25.55+/-4.56 mm in length. The mean vertical/horizontal distance ratio was 0.42+/-0.12. The mean size of the main pancreatic duct was 1.02x2.46 mm. The mean distribution coordinates of the main pancreatic duct were: X 51.23; Y 50.60. CONCLUSIONS: A proportional model of pancreatic isthmus cross section analysis is easy and effective, and could become a valuable tool in future anatomical studies. The system described allows us to analyze data acquired from several investigators. PMID- 17356242 TI - Evaluation of the bilio-pancreatic region using endoscopic ultrasonography in patients referred with and without abdominal pain and CA 19-9 serum level elevation. AB - CONTEXT: When assessing the bilio-pancreatic region, collating the findings of serum CA 19-9 values together with findings from various imaging tests- especially endoscopic ultrasonography--is not a simple issue in daily clinical practice. AIM: To assess the usefulness of endoscopic ultrasonography in an Endoscopic Ultrasonography Unit in two situations: patients with asymptomatic elevation of serum CA 19-9 and patients who presented with abdominal pain plus elevation of CA 19-9. METHODS: A retrospective study of those patients who underwent radial endoscopic ultrasonography between October 2004 and September 2005 in our institution, considering an elevation of CA 19-9 (equal to or greater than 37 U/mL) with or without symptoms. In each case, the parameters recorded were: levels of CA 19-9 one week before EUS, results from other imaging techniques (US, helical CT), and final diagnosis according to pathological and/or clinical evolution criteria. Patients with previous attacks of acute pancreatitis and also those who presented with bile duct dilation or space-occupying lesions in image studies (US and CT) were excluded. Twenty-two patients met the inclusion criteria. RESULTS: Asymptomatic elevation of CA 19-9 was found in 15 patients while 7 patients had elevated CA 19-9 levels as well as pain of uncertain origin. The results of EUS in the asymptomatic patients were: chronic pancreatitis in 7 patients, no pancreatic alterations in 3 patients, and renal cysts, choledocholithiasis, microlithiasis and liver cirrhosis in one patient, respectively. In patients with abdominal pain, EUS showed chronic pancreatitis in 6 cases and adenocarcinoma of the tail of the pancreas in the remaining patient. CONCLUSIONS: When EUS was indicated for the asymptomatic elevation of CA 19-9, the main findings were benign diseases. EUS was useful in studying patients with idiopathic abdominal pain and a slight elevation of CA 19-9 since it allowed us to detect chronic pancreatitis and even early adenocarcinoma of the pancreatic tail. PMID- 17356243 TI - Tropical chronic pancreatitis and peripheral vascular disease. A case report. AB - CONTEXT: It is well-known that subjects with diabetes resulting from tropical chronic pancreatitis are prone to diabetic microvascular complications (neuropathy, nephropathy and retinopathy). However, macrovascular complications (coronary artery disease, stroke and peripheral vessel disease) are rare, as these subjects are younger, leaner and have lower cholesterol levels. CASE REPORT: We report the case of a 51-year-old male who had tropical chronic pancreatitis, diabetes and severe peripheral vessel disease with gangrene. He was lean, had borderline lipid levels and was normotensive. His ECG was normal. CONCLUSIONS: Peripheral vascular disease can occur in these diabetic subjects, even without additional risk factors for atherosclerotic vascular disease. All subjects with tropical chronic pancreatitis and diabetes should have a complete foot examination once a year, in addition to screening for other vascular complications. PMID- 17356244 TI - Pancreatic and peripancreatic tuberculosis mimicking malignancy. AB - CONTEXT: There are a variety of differential diagnoses for an abnormal mass arising from the pancreas of which isolated pancreatic or peripancreatic tuberculosis is an extremely rare diagnosis with a variety of elusive presentations. CASE REPORT: We report such a case which masqueraded as malignancy in 43-year-old man presenting with jaundice, weight loss and new onset diabetes. CONCLUSIONS: Tuberculosis should be considered as a differential diagnosis to an obscure pancreatic mass which may result in local complications amenable to surgery. PMID- 17356245 TI - Intraductal oncocytic papillary neoplasm having clinical characteristics of mucinous cystic neoplasm and a benign histology. AB - CONTEXT: An intraductal oncocytic papillary neoplasm is a rare pancreatic tumor which was first described by Adsay et al. in 1996. It has been defined as a new subgroup of IPMN. CASE REPORT: We report the case of a 76-year-old woman who presented with nausea. Imaging studies revealed a cystic mass in the body of the pancreas. She underwent a successful distal pancreatectomy and splenectomy, and has subsequently remained well. Microscopically, the cyst was lined by columnar epithelium similar to pancreatic duct epithelium, and the nodular projection consisted of arborizing papillary structures, lined by plump cells with abundant eosinophilic cytoplasm. These eosinophilic cells were immunohistochemically positively stained with anti-mitochondrial antibody. The cellular atypism was mild and the proliferating index was low, compatible with adenoma of an intraductal oncocytic papillary neoplasm. Although no ovarian type stroma was identified, in our case, no communication to main pancreatic duct (located in the pancreatic body) and rapid growth by intracystic hemorrhage were clinical characteristics of a mucinous cystic neoplasm, but not IPMN. CONCLUSION: With only 17 cases reported to date, the clinical and pathological details of an intraductal oncocytic papillary neoplasm are still unclear. We herein add one case with different characteristics from those of the past reports. To our knowledge, this is the first case report of an intraductal oncocytic papillary neoplasm with the clinical characteristics of a mucinous cystic neoplasm. PMID- 17356246 TI - Metastasis of rectal adenocarcinoma to the pancreas. Two case reports and a review of the literature. AB - CONTEXT: The vast majority of pancreatic tumors are of pancreatic origin. Nonetheless, a variety of extrapancreatic tumors can involve the pancreas and may manifest with different clinicopathological characteristics. CASE REPORT: We report on two patients with a history of rectal cancer who were referred to our department with a pancreatic mass: one patient 2 years after a low anterior resection (TNM stage: pT3 pN0 pM0), the other patient 2.5 years after an abdominoperineal resection (TNM stage: pT3 pN1 pM0). In the first case, computed tomography showed a cystic mass in the pancreas but fine-needle biopsy followed by cytopathological analysis revealed only necrotic tissue. In the other patient, magnetic resonance tomography showed a hypodense structure in the pancreatic body/tail. Suspecting pancreatic tumors, distal pancreatectomies were carried out. Subsequent histological examination revealed metastases of rectal cancer in both cases. CONCLUSION: In patients with a history of a malignant tumor, a newly diagnosed mass in the pancreas--although rare--should raise the suspicion of metastatic disease. Surgical resection may be an option for a curative approach which can be offered to otherwise healthy patients if there is no evidence of other metastases. PMID- 17356247 TI - Liver metastasis four years after Whipple's resection for solid-pseudopapillary tumor of the pancreas. AB - CONTEXT: Solid-pseudopapillary tumor of the pancreas is a rare tumor which usually affects young females in their second and third decade of life. Metastasis is very rare after a resection of curative intent. CASE REPORT: We report a case of a 65-year-old white female who presented with metastasis to the liver four years after Whipple's resection for a solid-pseudopapillary tumor of the pancreas. CONCLUSIONS: Solid-pseudopapillary tumors of the pancreas can present with metastasis a long time after resection of the primary tumor. Long term close follow up of these patients should be done. The survival rate even after liver metastasis is good. PMID- 17356248 TI - Pancreatic mucinous cyst adenocarcinoma producing CA 19-9. A case report. AB - CONTEXT: We herein present a rare case of a mucinous cystic neoplasm of the pancreas producing CA 19-9 and the clinical implications are discussed. CASE REPORT: A 35-year-old woman with no history of abdominal surgery presented at Saisei Kai Sendai Hospital with an upper abdominal distention. Abdominal CT showed a large lobulated cystic tumor at the pancreatic tail. No distant metastases were identified. The preoperative serum CA 19-9 level was 6,200 U/mL (reference range: 0-37 U/mL). A mucinous cystic neoplasm of the pancreas was diagnosed and elective surgery was performed. On laparotomy, a round tumor 15 cm in diameter was encountered in the upper left abdomen. No invasion of neighboring organs or the portal vein was apparent. The entire tumor was curatively resected with a distal pancreatectomy. The final histopathological analysis revealed mucinous cystadenocarcinoma with no invasive component. Immunohistochemical staining disclosed CA 19-9 expression within the tumor cells. The CA 19-9 level normalized rapidly postoperatively and, although a minor pancreatic fistula occurred, this was resolved conservatively. She was discharged on the 45th postoperative day with no sign of tumor relapse; her CA 19-9 level was within the normal range 20 months postoperatively. CONCLUSION: We present this rare case of a mucinous cystic neoplasm producing CA 19-9 and discuss the relevant literature. The CA 19-9 production in this tumor does not appear to be directly correlated to aggressive clinical behavior. PMID- 17356249 TI - Epigastric mass due to a hydatid cyst of the pancreas. A case report and review of the literature. AB - CONTEXT: Primary hydatid disease of the pancreas is very rare. CASE REPORT: We report the case of a 30-year-old man who presented with abdominal pain and an epigastric mass. A diagnosis of a pancreatic cyst was established by ultrasonography and CT scan before surgery. The treatment consisted of the resection of the protruding dome with a cystogastrostomy. The recovery was uneventful and the patient has remained symptom free so far. CONCLUSIONS: Hydatid disease should be considered in the differential diagnosis of all cystic masses in the pancreas, especially in the geographical regions where the disease is endemic. PMID- 17356250 TI - Thrombosed splenic artery aneurysm simulating a pancreatic body mass: can two entities be distinguished preoperatively thus avoiding diagnostic and therapeutic mistakes? AB - CONTEXT: Splenic artery aneurysms are rare and they are usually easy to diagnose. Spiral computed tomography is the most sensitive diagnostic technique for this disease. Its primary treatment is interventional radiology; surgery is indicated in selected cases. CASE REPORT: We herein report a case of an elderly male patient with a completely thrombosed aneurysm of the splenic artery. The spiral computed tomography and color-Doppler ultrasonography findings were different; the first showed this entity to be a pancreatic solid tumor and the second showed it to be an aneurysmatic thrombosed dilation of the splenic artery. Thus, laparotomy was performed and the proper diagnosis was made. CONCLUSIONS: This case underlines the characteristics of completely thrombosed splenic artery aneurysm with the aim to avoid diagnostic and therapeutic mistakes. PMID- 17356251 TI - Supportive and palliative care of pancreatic cancer. AB - Pancreatic cancer is one of the most lethal malignancies. An estimated 32,300 patients will die of pancreatic cancer in year 2006. It is the tenth most common malignancy in the United States. Despite recent advances in pathology, molecular basis and treatment, the overall survival rate remains 4% for all stages and races. Palliative care represents an important aspect of care in patient with pancreatic malignancy. Identifying and treating disease related symptomology are priorities. As a physician taking care of these patients it is essential to know these symptoms and treatment modalities. This review discusses symptom management and supportive care strategies. Common problems include pain, intestinal obstruction, biliary obstruction, pancreatic insufficiency, anorexia-cachexia and depression. Success is needed in managing these symptoms to palliate patients with advanced pancreatic cancer. Pancreatic cancer is a model illness to learn the palliative and supportive management in cancer patient. It is important for oncologists to recognize the importance of control measures and supportive measures that can minimize the symptoms of advanced disease and side effects of cancer treatment. PMID- 17356252 TI - Pancreatic stellate cells and chronic alcoholic pancreatitis. PMID- 17356253 TI - Hyponatremia in community-acquired pneumonia. AB - BACKGROUND/AIM: Community-acquired pneumonia (CAP) is a frequent cause for hospitalization and may result in a number of different renal and electrolyte complications. The purpose of this study was to describe the incidence of hyponatremia in CAP and to analyze risk factors for its occurrence. METHODS: Records were reviewed for all 342 subjects who participated in the Community Acquired Pneumonia Standardized Order Set study, a 2-year trial of supplemental treatment tools in hospital pneumonia treatment. RESULTS: Hyponatremia (serum sodium concentration <136 mg/dl) was present at hospital admission in 27.9% of patients. The magnitude was generally mild, only 4.1% of patients had serum sodium <130 mEq/l. Patients with hyponatremia had greater initial heart rate (100.2 vs. 93.2 beats/min, p = 0.03), white blood cell count (15,100 vs. 12,100/mul, p < 0.0001) and pneumonia severity index class 4 or 5 (35.7 vs. 25.1% of patients, p = 0.05). Hyponatremia at admission was associated with greater risk for death and increased length of hospital stay. Hyponatremia developed during the hospitalization in 10.5% of subjects, with most cases being mild, only 2.6% of all patients having serum sodium decrease to <130 mEq/l. Patients developing hyponatremia were more likely to have end-stage renal disease and to have had initial intravenous fluids other than isotonic saline, but had similar severity of illness on admission to those without acquired hyponatremia. CONCLUSION: Hyponatremia is a common complication present at the time of admission for CAP. It is associated with more severe illness, increased mortality risk and extended hospital stays. Hyponatremia develops less frequently during the hospitalization and is unrelated to severity of illness on admission, but is an iatrogenic complication and thus initial treatment with isotonic saline may reduce the risk of this complication. PMID- 17356254 TI - Hepatitis C in chronic kidney disease: predialysis patients present more severe histological liver injury than hemodialysis patients? AB - BACKGROUND: The characteristics of hepatitis C virus (HCV) infection in predialysis patients are poorly understood and they could be different from hemodialysis patients. AIMS: To evaluate the demographics, laboratory and histological characteristics of chronic HCV infection in predialysis patients and to compare them with those observed in hemodialysis patients. METHODS: Thirty nine predialysis patients with chronic HCV infection were compared to HCV infected hemodialysis patients (ratio of 1:3) in terms of demographics, laboratory and histological characteristics. The fibrosis progression rate (FPR) was calculated as the ratio between fibrosis stage and duration of infection. RESULTS: Predialysis patients were older (57 +/- 10 vs. 45 +/- 12 years; p < 0.001), presented a higher proportion of elevated alanine aminotransferase (71.8 vs. 41.0%; p = 0.001) and aspartate aminotransferase (64.1 vs. 26.5%; p < 0.001), a higher proportion of interface hepatitis (66.7 vs. 47%; p = 0.033) and more advanced fibrosis (71.8 vs. 16.2%; p = 0.001). Among patients with estimated duration of infection, predialysis patients presented a longer duration of infection (22 vs. 6 years; p < 0.001) and no difference in FPR was observed between groups (p = 0.692). CONCLUSION: Although predialysis patients with HCV infection present more severe histological injury than hemodialysis patients, this finding probably reflects a longer duration of infection with no evidence supporting that hepatitis C presents a more aggressive course in this group. PMID- 17356255 TI - Influences of acute and chronic aerobic exercise on the plasma homocysteine level. AB - BACKGROUND AND AIMS: Elevated plasma homocysteine (PH) levels have been identified as a risk factor for cardiovascular diseases. The aims of this study were to investigate the influences of submaximal acute aerobic exercise and aerobic training on PH levels and lipid profiles. METHODS: 69 volunteer subjects (21.12 +/- 2.08 years) were randomized to three groups as acute, training and control groups. Examination and blood samples were collected before and immediately after exercise in the acute group and before and 6 weeks later in the training and control groups. RESULTS: A significant increase in PH concentration was recorded immediately after aerobic exercise, compared with baseline values (p = 0.001). Although, in the training group, total cholesterol (p = 0.00) and LDL cholesterol (p = 0.001) decreased significantly after training, no significant changes in PH concentration, HDL cholesterol (p = 0.087) and triglyceride (p = 194) levels were found. CONCLUSIONS: It can be said that the PH level increases following submaximal acute aerobic exercise, but does not alter after submaximal aerobic training due to training duration or intensity. Therefore, submaximal aerobic training decreases lipid profiles independent of the PH level. PMID- 17356256 TI - Prevalence and impact of vitamin D insufficiency in southern Chinese adults. AB - INTRODUCTION: Vitamin D is a vital element for bone health but the problem of vitamin D deficiency is underestimated in Hong Kong. METHODS: Serum 25(OH)D and parathyroid hormone (PTH) levels were evaluated in 382 community dwelling Chinese adults >50 years for their relation with bone mineral density (BMD) and risks of osteoporotic fractures and falls. RESULTS: The mean age of the subjects was 69 +/ 9 years. The mean 25(OH)D level was 28.3 +/- 10.8 ng/ml with 62.8% of the subjects having levels <30 ng/ml. 6.3% of the subjects had elevated PTH levels. A curvilinear relation between serum PTH and 25(OH)D was found, with PTH starting to increase when 25(OH)D level fell below 30 ng/ml (r = -0.233, p < 0.05). Although subjects with vitamin D <30 ng/ml had significantly lower BMD, only sex, age and PTH but not 25(OH)D were predictors of BMD at the spine and hip. Subjects with elevated PTH levels had a 2.92-fold increased risk of falls and 2.94-fold increased risk of fractures at the hip and spine. CONCLUSIONS: Vitamin D insufficiency and its complication of secondary hyperparathyroidism is common even in subtropical region and is an important risk factor for low bone mass, falls and fractures. PMID- 17356257 TI - Effects of bioactive peptide, valyl-prolyl-proline (VPP), and lactobacillus helveticus fermented milk containing VPP on bone loss in ovariectomized rats. AB - BACKGROUND: Valyl-prolyl-proline (VPP), a bioactive peptide formed during the fermentation with Lactobacillus helveticus LBK-16H (L. helveticus), has been shown to increase bone formation in vitro. The aim of the study was to determine whether VPP and L. helveticus fermented milk prevent bone loss in ovariectomized (OVX) rats. METHODS: During the 12-week intervention study, the OVX rats received VPP in water or L. helveticus fermented milk, containing VPP. Sham-operated rats receiving water acted as controls. The trabecular and cortical bone mineral density were determined by peripheral quantitative computed tomography before the operation and at 4 and 12 weeks. The mechanical testing and ash weight analysis as well as the static and dynamic histomorphometrical parameters were assessed at the end of the intervention. RESULTS: VPP given in water showed no clear effect on bone loss. L. helveticus fermented milk prevented bone loss by decreasing bone turnover and increasing the bone mineral density. Ovariectomy caused a 57% loss in the trabecular bone, which was attenuated by 16% in the L. helveticus group. CONCLUSIONS: VPP peptide did not prevent ovariectomy-induced bone loss, which could be due to the poor bioavailability of VPP from water solution. L. helveticus fermented milk prevented bone loss, whether this is due to the VPP peptide cannot be concluded. PMID- 17356258 TI - Weight loss and quality of life improvement in obese subjects treated with sibutramine: a double-blind randomized multicenter study. AB - BACKGROUND AND AIM: Obesity affects cardiovascular risk and also quality of life (QoL). The aim of this study was to test weight loss and impact on QoL after sibutramine treatment in obese subjects. METHODS: Double-blind randomized trial on 309 outpatients (51 males, 258 females; age 41.8 +/- 10.9 years, BMI 35.0 +/- 3.1 kg/m(2)) randomized to sibutramine (n = 154) or to placebo (n = 155) treatment. A combination of sibutramine 10 mg or matching placebo and a balanced hypocaloric diet was given for 6 months with monthly evaluations. The main outcome measures were weight loss, the impact of weight on QoL, BMI, and waist circumference. RESULTS: The mean weight reduction was 8.2 kg in the sibutramine group and 3.9 in the placebo group at 6 months (p < 0.01). 40% of the sibutramine subjects and 14% of the control subjects lost > or =10% of their body weight (p < 0.01). The improvement in the impact of weight on QoL was statistically significant only in the sibutramine group at 6 months (mean -12.5 vs. -4.5 points; p < 0.01). In the sibutramine group the reduction in BMI (-3.1 vs. -1.4 kg/m(2)) and waist circumference (7.7 vs. 3.5 cm) was significantly greater (p < 0.001). The incidence of adverse events was low and similar to the placebo. CONCLUSIONS: This study confirmed that sibutramine significantly enhances the effect of diet on weight loss, BMI and waist circumference reduction, and showed a significant improvement of QoL. PMID- 17356259 TI - Study of homocysteine concentration in coronary heart disease patients and comparison of two determination methods. AB - INTRODUCTION: Elevated total homocysteine (tHCY) is a known risk factor for atherosclerotic vascular disease, but the mechanism is not well understood. The study was designed to estimate tHCY concentration and other risk factors in coronary heart disease (CHD) males, evaluating two different methods for tHCY measurement: gas chromatography-mass spectrometry (GC-MS) method and competitive immunoassay method. MATERIALS AND METHODS: Fifty men, mean age 53.9 years with CHD and a body mass index (BMI) >25.0, were examined for tHCY concentrations, lipids, blood glucose, uric acid, complete blood picture and erythrocyte sedimentation rate and high-sensitive C-reactive protein (hsCRP). Biochemical and hematological indices were determined by routine methods, hsCRP--by immunometric chemiluminescence method, and tHCY--by two different methods: a gas chromatographic method, using GC-MS and a competitive immunoassay method on an Immulite device. RESULTS: The mean values of the lipids showed moderate dyslipidemia while the other parameters were within reference range. Mean BMI was 28.5 +/- 0.42. Values of tHCY determined by the immunoassay method were 13.2 +/- 0.95 micromol/l, and determined by GC-MS - 14.6 +/- 1.09 micromol/l. We found a linear agreement between the DPC and GC-MS sets of measurements (r = 0.87, p < or = 0.001). The median tHCY concentrations measured by immunoassay were lower than those measured with GC-MS, but differences were insignificant. An agreement between the competitive immunoassay and the GC-MS method evaluated by the Bland and Altman method was found. tHCY was >15 micromol/l in 12 patients as determined by the competitive immunoassay, and in 15 patients by the GC-MS method. tHCY levels were between 10 and 15 micromol/l in 24 patients by the immunoassay and in 29 patients by the GC-MS method. Twenty-four percent of the patients with CHD have an 'increased risk' with tHCY >15 micromol/l, and 48% are in the 'gray zone' with tHCY levels between 10 and 15 micromol/l. CONCLUSIONS: 40.8% of the studied patients had increased tHCY levels, not associated with the other lipid and nonlipid risk factors. The closest conformity between GC-MS and immunoassay methods was observed for serum tHCY concentrations. The between-method comparison reveals that the above-mentioned methods can be used interchangeably. PMID- 17356260 TI - Resting metabolic rate of elderly Vietnamese. AB - BACKGROUND/AIMS: To evaluate the FAO/WHO/UNU equations for predicting resting metabolic rate (RMR) in elderly Vietnamese. METHODS: A cross-sectional study involving healthy and elderly subjects was carried out at the Basic Nutrition Department, National Institute of Nutrition, Vietnam. A total of 75 subjects who had a normal body mass index (BMI) were divided into two groups according to sex. The RMR was measured by indirect calorimetry and anthropometric indices were recorded. Equations derived by linear regression of RMR and body weight were compared to the FAO/WHO/UNU (1985) predictive equations. RESULTS: The mean age of males and females were 65.03 +/- 4.0 and 66.48 +/- 4.61 years, respectively. Mean RMRs (MJ/kg/day) were 0.0963 +/- 0.0121 for males and 0.0925 +/- 0.0117 for females. Compared to the FAO/WHO/UNU equations, our findings were 10.9 and 11.1% lower in males and females, respectively (p < 0.05). CONCLUSION: Our findings suggest that the FAO/WHO/UNU equations may overestimate RMR in elderly Vietnamese. Further studies to find out the most appropriate equation or to establish new predictive equations for RMR in elderly Vietnamese should be conducted. PMID- 17356261 TI - Acute effect of leptin and ghrelin injection on postprandial glycogen and lipid synthesis in rats. AB - AIM: The study was designed to investigate the immediate (1 h) effect of leptin and ghrelin injection on in vivo postprandial hepatic glycogen and lipid synthesis. ANIMALS AND METHODS: Adult Sprague-Dawley male rats were fed a semisynthetic control diet ad libitum. Overnight-fasted rats were gavaged with 4 ml of water containing 1.25 g of the diet and immediately injected intraperitoneally with 4 mCi of (3)H(2)O. After 1 h, rats were either intraperitoneally injected with saline (control), leptin (20 microg/rat) or ghrelin (10 microg/rat) and sacrificed 1 h later. Blood, liver and epididymal fat pads (EFP) were taken for analysis. RESULTS: Plasma triglyceride level was higher in the leptin group compared to control. Leptin injection reduced hepatic glycogen synthesis while glycogen accumulation was not affected and ghrelin injection did not affect hepatic glycogen synthesis. Both hepatic and EFP lipogenesis were not affected by leptin or ghrelin. CONCLUSION: Leptin and ghrelin administration had no immediate effect on hepatic and adipose tissue lipogenesis. Leptin reduced in vivo postprandial hepatic glycogenesis and increased plasma triglyceride level which may be due to reduced uptake by peripheral tissues. Thus, leptin was found to exert an immediate effect on lipid and carbohydrate metabolism unlike that of ghrelin. PMID- 17356262 TI - NO2/NO3 plasma profile under different parenteral nutrition regimens in newborns. AB - OBJECTIVE: Free radical production is increased by the administration of total parenteral nutrition (TPN) and may be linked to its adverse effects. Some of the complications of TPN can be ameliorated by partial enteral feeding. In the present study, we investigated plasma nitrate/nitrite (NO(2)/NO(3)) levels in newborns under parenteral and enteral plus parenteral nutrition (PN). STUDY DESIGN: Six categories of patients were studied: (1) 10 term infants receiving enteral feeding, (2) 10 term infants receiving PN plus enteral feeding, (3) 10 term infants receiving TPN, (4) 10 preterm infants receiving enteral feeding, (5) 10 preterm infants receiving PN plus enteral feeding, and (6) 10 preterm infants receiving TPN. Plasma nitrate/nitrite levels were measured in all infants initially and in infants receiving TPN and PN plus enteral feeding on the 1st and 5th days, 3 h after the lipid infusion. RESULTS: There was a statistically significant difference in the weighs of infants between the term and preterm groups. There was no difference in NO(2)/NO(3) levels between the term and preterm groups. When the groups of term (groups 1, 2, 3) and preterm (groups 4, 5, 6) infants were compared separately within the groups, no statistically significant difference was found in any parameters. We also made comparison among the six groups' gestational ages, and we found a difference between all term groups and all preterm groups except between groups 1 and 2; groups 1 and 3; groups 2 and 3; groups 4 and 5, and groups 5 and 6 (p < 0.05). Furthermore, the baseline, 1st and 5th days NO(2)/NO(3) levels were compared in the term and preterm groups receiving PN. Plasma NO(2)/NO(3)levels before TPN were significantly lower in the term infants receiving parenteral fluids compared with NO(2)/NO(3) levels of 1st day of TPN (p < 0.05). In preterm infants receiving TPN the NO(2)/NO(3) levels before TPN were significantly lower than the levels on the 5th day of PN (p < 0.05). There was no significant difference among other NO(2)/NO(3) levels of the patients at baseline, 1st and 5th days in the term and preterm groups. Partial enteral feeding did not change the levels of NO(2)/NO(3) in term and preterm infants on PN. CONCLUSION: This study shows that TPN has some impact on nitric oxide (NO) production in newborn and partial enteral nutrition does not reduce this effect. However, since the numbers are very small these findings need to be verified by larger groups of patients. PMID- 17356263 TI - Effect of dietary alpha-linolenic fatty acid derived from chia when fed as ground seed, whole seed and oil on lipid content and fatty acid composition of rat plasma. AB - Coronary heart disease (CHD) is the most common cause of death in the Western world. In both the USA and the EU it accounts for over 600,000 deaths yearly. Early data showing the benefits n-3 fatty acids provide in preventing CHD disease were obtained using 20:5n-3 and 22:6n-3 fatty acids derived from fish. Recently, however, it has been shown that reduced risks of CHD and other cardiovascular diseases are found with 18:3n-3 fatty acid as well. To determine if 18:3n-3 fatty acids positively influence plasma composition, 32 male Wistar rats were fed ad libitum four isocaloric diets with the energy derived from corn oil (T(1)), whole chia seed (T(2)), ground chia seed (T(3)), or chia oil (T(4)) for 30 days. At the end of the feeding period the rats were sacrificed, and blood samples were analyzed to determine serum CHOL, HDL, LDL, TG content, hemogram, and fatty acid composition. Chia decreased serum TG content and increased HDL content. Only with the T(2) diet was TG significantly (p < 0.05) lower, and only with the T(3) diet was HDL significantly (p < 0.05) higher, than the control diet. Chia significantly (p < 0.05) increased the 18:3n-3, 20:5n-3 and 22:6n-3 plasma contents compared to the control diet, with no significant (p < 0.05) difference among chia diets detected. Significant (p < 0.05) improvement in n-6/n-3 fatty acid ratio was observed for all chia diets when compared to the control. PMID- 17356264 TI - Ultrasonographic measurement of intra-abdominal fat thickness in HIV-infected patients treated or not with antiretroviral drugs and its correlation to lipid and glycemic profiles. AB - AIMS: To compare the intra-abdominal fat thickness measured by ultrasound between HIV-infected patients treated or not with antiretroviral drugs and to correlate these visceral adiposity measurements to other parameters of cardiovascular risks. METHODS: In a transversal observational study, 160 HIV-infected patients were recruited and divided in two groups, i.e., 123 antiretroviral (ARV)-treated and 37 ARV-naive patients. These patients were submitted to anthropometric determinations, laboratorial analysis, ultrasonographic measurements of subcutaneous and intra- abdominal fat thickness and to tetrapolar bioelectrical impedance analysis in order to measure the body composition. RESULTS: In the patients treated with highly active antiretroviral therapy (HAART) the intra abdominal fat pad was significantly thicker than that of the untreated group (69 +/- 21 mm, n = 123 vs. 60 +/- 18 mm, n = 37; p = 0.03 Student's t test). The intra-abdominal fat thickness correlated significantly with plasma triglyceride, total cholesterol, fasting glucose, glucose measurements 2 h after dextrose load, fasting insulin, HOMA-IR index, systolic and diastolic blood pressures, weight, BMI, WHR and caliper-measured total fat percentage. CONCLUSION: The results showed that antiretroviral therapy is associated with increased ultrasonographic measurements of visceral adiposity. Our data demonstrated a strong correlation between intra-abdominal fat thickness and independent risk factors of cardiovascular disease: atherogenic lipid profile and insulin resistance. PMID- 17356265 TI - Soy protein and isoflavones influence adiposity and development of metabolic syndrome in the obese male ZDF rat. AB - BACKGROUND/AIMS: Previously, we demonstrated that soy protein ameliorates the diabetic phenotype in several rodent models of obesity and metabolic syndrome (MS). This study was designed to further elucidate factors related to adiposity, glycemic control, and renal function in male Zucker Diabetic Fatty (ZDF/Lepr(fa)) rats. METHODS: Animals were randomly assigned to one of four diets: control, casein (C); low isoflavone (LIS) soy protein; high isoflavone (HIS) soy protein, or casein + rosiglitazone (CR) for 11 weeks. At sacrifice, physiological, biochemical, and molecular parameters were determined. RESULTS: Body weight and total adiposity were higher in LIS and CR diet groups despite lower food intake. Additionally, these animals exhibited differential regulation of adipose-specific proteins (PPAR-gamma and GLUT4) and enzyme activity (FAS and GPDH). HIS-fed animals had reduced total and liver adiposity. Glycemic control was prolonged in both soy-based and rosiglitazone (RGZ) groups. Renal dysfunction was significantly reduced in soy-fed and RGZ-treated rodents as demonstrated by lower levels of proteinuria and dilated tubules with proteinaceous casts. CONCLUSION: Collectively, these data provide evidence that soy protein with low or high isoflavone content may have therapeutic significance in reducing severity of diabetes, MS, and renal disease as demonstrated in this preclinical model. PMID- 17356266 TI - Induction of apoptosis by (Z)-stellettic acid C, an acetylenic acid from the sponge Stelletta sp., is associated with inhibition of telomerase activity in human leukemic U937 cells. AB - BACKGROUND: (Z)-stellettic acid C, an acetylenic acid from the marine sponge Stelletta sp., has been shown to have cytotoxic activity in some cancer cells; however, its mechanisms on malignant cell growth are not known. In this study, the potential of (Z)-stellettic acid C to induce apoptosis in human leukemic U937 cells and its effects on telomerase activity were investigated. METHODS: Cytotoxicity was evaluated by MTT assays. Apoptosis was detected using DAPI staining and annexin V fluorescein. The mRNAs of Bcl-2, inhibitor of apoptosis proteins (IAPs) family and Fas/FasL system were determined by RT-PCR. Caspases and telomerase activities were measured using colorimetric assay and telomeric repeat amplification protocol enzyme-linked immunosorbent assay (TRAP-ELISA), respectively. RESULTS: Exposure of U937 cells to (Z)-stellettic acid C resulted in growth inhibition and induction of apoptosis in a dose-dependent manner, which was associated with the modulation of Bcl-2 family expression, activation of caspases and downregulation of IAPs family members. (Z)-Stellettic acid C treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the expression of human telomerase reverse transcriptase, a main determinant of the telomerase enzymatic activity, was progressively downregulated by (Z)-stellettic acid C treatment. CONCLUSIONS: These results suggest that (Z)-stellettic acid C could have a possible cancer therapeutic potential. PMID- 17356267 TI - Possible role of sarA in dehydroepiandrosterone-mediated increase in Staphylococcus aureus resistance to vancomycin. AB - BACKGROUND: Dehydroepiandrosterone (DHEA), a steroid present throughout life, can induce an increase in resistance to vancomycin in methicillin-sensitive and methicillin-resistant clinical isolates of Staphylococcus aureus. METHODS: The in vitro effect of DHEA on vancomycin killing of S. aureus with mutations in sarA and/or agr was determined by standard microtiter protocols and time to kill determinations. RESULTS: Of the isolates tested, the strain with a deletion in sarAderived from a DHEA- responsive parent was not protected from vancomycin killing by DHEA. However, DHEA significantly (p < 0.01) slowed the rate of vancomycin killing of sarA-. CONCLUSION: These data indicate that sarA may play a role in DHEA-mediated protection from vancomycin killing of S. aureus. PMID- 17356268 TI - Role of ciprofloxacin in its synergistic effect with fosfomycin on drug-resistant strains of Pseudomonas aeruginosa. AB - BACKGROUND: The aim of this study was to investigate the synergistic effect of ciprofloxacin (CPFX) and fosfomycin (FOM) on CPFX-resistant Pseudomonas aeruginosa strains. METHODS: The synergistic effect was evaluated using the fractional inhibitory concentration index, acute bactericidal effect and morphological observation. RESULTS: In the fractional inhibitory concentration index experiments, the combination of CPFX with FOM showed a synergistic effect in 20 of 74 (27.0%) strains of P. aeruginosa. From the morphological observations, it was determined that CPFX affected the outer membrane structure. CPFX combined with FOM caused striking morphological changes, resulting in bacteriolysis. A time lag experiment suggested that the addition of CPFX prior to FOM produced more pronounced bactericidal activity than the addition of FOM prior to CPFX. CONCLUSIONS: These results indicate that the combination of CPFX with FOM induces a synergistic effect on CPFX-resistant P. aeruginosa strains. The role of CPFX is thought to be related to damage of the outer membrane, enhancing FOM penetration. PMID- 17356269 TI - Sulfasalazine-induced reduction of glutathione levels in breast cancer cells: enhancement of growth-inhibitory activity of Doxorubicin. AB - BACKGROUND: We previously showed that the anti-inflammatory drug, sulfasalazine (salicylazosulfapyridine, SASP), can arrest proliferation of MCF-7 and MDA-MB-231 mammary cancer cells by inhibiting uptake of cystine via the x(c-) cystine/glutamate antiporter. Here we examined SASP with regard to reduction of cellular glutathione (GSH) levels and drug efficacy-enhancing ability. METHODS: GSH levels were measured spectrophotometrically. Cellular drug retention was determined with 3H-labeled methotrexate, and drug efficacy with a colony formation assay. RESULTS: Incubation of the mammary cancer cells with SASP (0.3 0.5 mM) led to reduction of their GSH content in a time- and concentration dependent manner. Similar to MK-571, a multidrug resistance-associated protein inhibitor, SASP increased intracellular accumulation of methotrexate. Preincubation of cells with SASP (0.3 mM) significantly enhanced the potency of the anticancer agent doxorubicin (2.5 nM). CONCLUSIONS: SASP-induced reduction of cellular GSH levels can lead to growth arrest of mammary cancer cells and enhancement of anticancer drug efficacy. PMID- 17356270 TI - In vitro AN69 and polysulphone membrane permeability to ceftazidime and in vivo pharmacokinetics during continuous renal replacement therapies. AB - BACKGROUND: Ceftazidime is a third-generation cephalosporin almost entirely eliminated by glomerular filtration and dose reductions are essential in patients with renal impairment. The physicochemical and pharmacokinetic properties of ceftazidime make it susceptible to be eliminated by continuous renal replacement therapies (CRRT), but there is little clinical information to guide the correct administration in patients undergoing these techniques. METHODS: In vitro procedures were carried out in three different fluids, using AN69 or polysulphone membranes. Four patients entered the in vivo study. Two patients received 1,000 mg every 6 h and the other two 2,000 mg every 6 h. Concentrations of ceftazidime were measured by high-performance liquid chromatography. RESULTS: No differences were detected in thesieving coefficients (Sc) or saturation coefficients (Sa)between membranes during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHD). Sc-Sa values were close to 1 when Ringer's lactate was used as ceftazidime vehicle, but were lower in plasma samples (p < 0.05). In patients, the Sc-Sa was 0.93 +/- 0.06 and correlated well with the unbound fraction (0.86 +/- 0.08). The contribution of CRRT to ceftazidime clearance was higher in anuric patients than in nonanuric patients. CONCLUSIONS: No differences were shown in vitro in the Sc obtained with both membranes during CVVH or the Sa obtained during CVVHD. The contribution of clearance by CRRT to total clearance is clearly dependent on the renal function. The administration of ceftazidime every 6 h could be associated with unnecessarily high trough levels which increase the risk of drug nephrotoxicity. Nonanuric patients undergoing CRRT need higher ceftazidime doses to reach adequate plasma concentrations against pathogens isolated in the critically ill. PMID- 17356271 TI - Retrospective evaluation of sequential outpatient chemotherapy for advanced gastric cancer. AB - BACKGROUND/AIM: Due to the recent development of several promising chemotherapeutic agents, such as S-1, irinotecan (CPT-11) and paclitaxel, response rates for advanced gastric cancer to chemotherapy have improved. Thus far, however, the efficacy and survival benefits of sequential chemotherapy using these agents have not been evaluated. An additional benefit of outpatient sequential chemotherapy, that is, without hospitalization, would be its contribution to the maintenance of patients' social activities. The aim of this study was to retrospectively evaluate sequential outpatient chemotherapy for advanced gastric cancer. PATIENTS AND METHODS: Patients with metastatic/recurrent gastric cancer treated with sequential outpatient chemotherapy were analyzed retrospectively. The sequential treatment consisted of S1-based chemotherapy as first-line therapy, low-dose CPT-11/CDDP as second-line therapy and weekly paclitaxel administration as third-line therapy. RESULTS: A series of 32 patients was enrolled in this study. During the sequential chemotherapy, all patients were treated at the outpatient ward of Kyoto University Hospital without hospitalization. The overall response rate was 37.5% and the median survival time was 523 days (95% confidence interval: 323-723 days). The progression-free survival for the three therapies was 135 days for S-1, 148 days for low-dose CPT 11/CDDP and 57 days for paclitaxel. Grade 4 neutropenia was observed in 1 patient (3.1%), and there were no treatment-related deaths. Univariate analysis showed that factors with significant impact on survival were pathological type (intestinal vs. diffuse), clinical response (responder vs. non-responder) and prior chemotherapy. Factors with p values <0.1, including pathological type, clinical response, prior chemotherapy and age (>75 vs. < or =75 years), were evaluated by multivariate analysis, which disclosed that clinical response and patient age were significantly related to patient prognosis. CONCLUSION: In terms of survival and maintenance of social activities of patients, outpatient sequential chemotherapy appears to be both feasible and effective for advanced gastric cancer. Although prospective analysis of sequential chemotherapy is difficult because of its complex treatment protocol, clinical trials to assess the survival benefits of second-line chemotherapy for advanced gastric cancer are clearly warranted. PMID- 17356272 TI - Preclinical dementia: an Italian multicentre study on amnestic mild cognitive impairment. AB - BACKGROUND: Different rates and cognitive predictors of conversion to dementia have been reported in subjects with different kinds of mild cognitive impairment (MCI). METHODS: A prospective, 24-month follow-up study, involving 269 subjects who strictly fulfilled criteria for the amnestic MCI. RESULTS: Conversion rate to dementia was 21.4% per year. Seventy-nine out of the 83 individuals who developed dementia were affected by probable Alzheimer's disease (AD). Among others, at the 24-month follow-up 24.1% were still affected by amnestic MCI, 13.3% had changed their neuropsychological profile of impairment and 17.2% were cognitively normalised. Compared to subjects who did not convert to AD, those who did convert showed poorer immediate and delayed recall and recognition of verbal and visual material at baseline as well as reduced executive abilities. A combination of age, Clinical Dementia Rating boxes and scores on delayed recall and recognition of verbal and visual material accurately identified 86% of the subjects who developed AD. CONCLUSIONS: Elderly subjects affected by an isolated memory disorder have a high probability of developing AD. The ability of verbal and visual measures to predict incipient dementia of memory impairment may be increased by the simultaneous assessment of individual features, such as age or rate of functional impairment. PMID- 17356273 TI - Domain-specific improvement of cognition on memantine in patients with Alzheimer's disease treated with rivastigmine. AB - OBJECTIVE: Cholinergic therapy is used in mild-to-moderate Alzheimer's disease (AD) and antiglutamatergic therapy in moderate-to-severe AD. Global scales, as commonly used in clinical trials, blur specifics of disease progression and drug effects. The objective was to assess combination therapy of rivastigmine plus memantine by specific neuropsychological tests in patients with mild-to-moderate AD. METHODS: 12-week-short multicenter open-label pilot study. Ninety patients with mild-to-moderate AD already on stable medication with rivastigmine (3-6 mg b.i.d.) additionally received memantine for 12 weeks. Subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE) and additional neuropsychological tests (e.g. span tasks, semantic fluency) were assessed. RESULTS: The scores in the ADAS-cog memory subscale, the MMSE score, and digit span and semantic fluency significantly improved on combination therapy. CONCLUSION: Memory improvement was correlated with ADAS-cog memory score at baseline and inversely with age at onset of treatment. The data suggest that improvement on combination therapy results from an improvement of attention/executive function with secondary memory improvement, which will need to be confirmed in a subsequent double-blind study on a larger number of patients. PMID- 17356274 TI - Treatment of delusions in dementia with Lewy bodies - response to pharmacotherapy. AB - BACKGROUND: Delusions are clinically important symptoms in dementia with Lewy bodies (DLB). The purpose of this review is to examine the level of evidence for treatment of delusions in DLB. METHODS: To achieve this objective Medline was searched. Studies were included in the review if they were prospective, separated delusions from hallucinations and were tested in patients with DLB. RESULTS: The review yielded a total of six studies. Although all studies showed effectiveness, only one study using rivastigmine had an adequate patient sample size and used a randomized controlled design. CONCLUSION: Further studies are required before a definitive conclusion can be reached about effective treatments. PMID- 17356275 TI - HSPG2 gene C/A polymorphism does not confer susceptibility to Alzheimer's disease in Chinese. AB - Human HSPG2 participates in the formation of amyloid and tau aggregation in Alzheimer's disease (AD). HSPG2 gene is located on a susceptibility region to late-onset AD (LOAD), and considered as a candidate gene for LOAD because of its function and location. We performed an association study between the HSPG2 BamH I polymorphism C/A of intron 6 and LOAD on 104 patients and 127 healthy controls of Chinese origin. The C allele was more prominent in LOAD patients than in controls, though the difference was not statistically significant. Likewise with the stratification of APOE epsilon4 status, no statistical difference was observed between cases and controls. Our findings suggest that this polymorphism may not represent an additional genetic risk factor for LOAD. PMID- 17356276 TI - The beginning of a new era. PMID- 17356277 TI - Merits and problems in high-threshold methadone maintenance treatment. Evaluation of medication-assisted rehabilitation in Norway 1998-2004. AB - BACKGROUND: Methadone maintenance treatment (MMT) in Norway emphasizes rehabilitation and control with strict intake criteria and rules for involuntary termination. Consequently, the programme should be characterized as high threshold and restrictive, which is somewhat out of tune with the general European trend towards harm reduction and diversity. METHODS: The programme has undergone an extensive evaluation with quantitative and qualitative methods. FINDINGS: MMT is at present integrated into the general health and social security system. The restrictive traits have not prevented rapid development in the capacity and coverage. Results on retention and drug use are above average for MMT programmes, but results on vocational rehabilitation are not impressive. The system is costly and some inherent structural problems cause concern. CONCLUSION: On this basis, central authorities have decided to keep the core structure of the programme, but to implement several changes. Medical diagnosis and evaluation should replace formal regulating criteria. PMID- 17356278 TI - Identification of patients at high risk of noncompliance in substance dependence treatment. AB - Noncompliance in substance dependence treatment seriously threatens its effectiveness. Pretreatment identification of those at the highest risk allows targeting of specific compliance enhancing interventions to those who may benefit most from it. In a cohort of 292 patients entering a 30-day treatment program for substance abuse treatment, several potential predictors of noncompliance were recorded before treatment. Compliance was registered when treatment was discontinued before the 30th day. Logistic regression was used to identify independent predictors of noncompliance and the area under the receiver-operating characteristic (ROC) curve was quantified to assess their joint predictive value. Mean age was 35 years, 80% were male. During follow-up 31% became noncompliant. Independent predictors of noncompliance were male gender, less than 10 years of education, severity of medical and drug problems, and behavioral intention to comply with treatment. The area under the ROC curve was 0.70 (95% CI: 0.64-0.76). In conclusion, noncompliance in a substance abuse treatment program can be predicted using five easy to assess patient characteristics. These results may be useful in preventing noncompliant behavior early in treatment by motivational counseling strategies. PMID- 17356279 TI - Psychometric evaluation of the Dutch version of the Subjective Opiate Withdrawal Scale (SOWS). AB - AIM: To evaluate the psychometric properties of the Dutch version of the 16-item Subjective Opiate Withdrawal Scale (SOWS). The SOWS measures withdrawal symptoms at the time of assessment. METHODS: The Dutch SOWS was repeatedly administered to a sample of 272 opioid-dependent inpatients of four addiction treatment centers during rapid detoxification with or without general anesthesia. Examination of the psychometric properties of the SOWS included exploratory factor analysis, internal consistency, test-retest reliability, and criterion validity. RESULTS: Exploratory factor analysis of the SOWS revealed a general pattern of four factors with three items not always clustered in the same factors at different points of measurement. After excluding these items from factor analysis four factors were identified during detoxification (temperature dysregulation, tractus locomotorius, tractus gastro-intestinalis and facial disinhibition). The 13-item SOWS shows high internal consistency and test-retest reliability and good validity at different stages of withdrawal. CONCLUSION: The 13-item SOWS is a reliable and valid instrument to assess opioid withdrawal during rapid detoxification. Three items were deleted because their content does not correspond directly with opioid withdrawal symptoms. PMID- 17356280 TI - Trait aggression and hostility in recovered alcoholics. AB - There is a long-recognized association between alcohol consumption and aggressive behavior. This study was designed to examine aggression in a group of socially well-adapted recovered alcoholics (RA). The question addressed was whether the treatment, together with long-term abstinence from alcohol, could reduce aggression and hostility in RA. A group of male RA (n = 64), who did not meet the DSM-IV criteria for any psychiatric or personality disorder, were recruited to the study from aftercare groups. According to data from their group therapists, they were reliably abstinent for at least 3 years and socially well adapted. The study participants representing the control group (n = 69), diagnosed as being 'reliable nonalcoholics' (NA) by the Munich Alcoholism Test, were recruited from general practice. Data were derived from an in-house questionnaire on general characteristics of both groups, and aggressive and hostility traits were assessed using the Buss-Durkee Hostility Inventory (BDHI). The univariate and multivariate between-groups design was used for data analysis. Taking into account the BDHI dimensions of aggression and hostility, the difference between RA and NA groups was statistically significant [Wilks' lambda (8, 125) = 0.769; p = 0.00004]. There were statistically significant differences in the BDHI scales for indirect aggression, irritability, negativism, suspicion, resentment, and guilt. Both RA and Na groups did not differ significantly in variables that assessed physical and verbal aggression. After a 3-year abstinence, subjects from the RA group displayed signs of hostility and covert aggression. PMID- 17356281 TI - Developmental outcome in children with intrauterine exposure to substances. AB - The developmental outcome of children born to Swiss substance-dependent mothers in a residential treatment program was studied in a sample of 61 children ranging from infancy to preadolescence (mean age = 5.10, SD = 3.10 years) by use of age appropriate tests of intelligence. A large list of biological and psychosocial risk factors was tested for associations with outcome in the children. The mean profile of test findings across all age ranges was significantly lower than population norms and there was an excess of children with subnormal intellectual functioning. Performance IQ was associated negatively only with intrauterine substance exposure, but with none of the other risk factors. Among the various substances, predominantly heroin or methadone were responsible for this association when controls for nicotine or cannabis consumption were made. The study provides further evidence that intrauterine exposure to heroin and methadone negatively affects the developmental outcome in the offspring of substance-dependent mothers. PMID- 17356282 TI - Attachment styles in alcoholic inpatients. AB - Despite the fact that addiction has often been identified as an attachment disorder, empirical studies on this topic are rather scarce. In our study we explore attachment style (secure vs. insecure) in alcoholic inpatients and its relationship with perceived parenting and alcohol-related and psychiatric problems in a sample of 101 alcoholic inpatients (Belgium). Our results reveal that in comparison to the securely-attached group, insecurely-attached alcoholic inpatients perceived their mother as more controlling, reported more severe psychiatric problems in the European Addiction Severity Index, had higher scores on the Beck Depression Inventory, showed more schizotypal and depressive personality traits and had more difficulties with communicating emotions (alexithymia). We argue that it makes sense to differentiate alcoholic inpatients on the basis of attachment style and that both groups (secure/insecure) need different treatment approaches. PMID- 17356283 TI - Anxiety disorders: treatable regardless of the severity of comorbid alcohol dependence. AB - AIMS: Clinical and epidemiological research has shown that comorbidity is the rule rather than exception in the case of psychiatric disorders. Cognitive behavioral therapy (CBT) has been clearly demonstrated to be effective in treating anxiety and avoidance symptoms in patient samples of social phobia and agoraphobia without comorbid alcohol use disorders. It has recently been shown that treatment of comorbid anxiety disorders in alcohol-dependent patients can also be very successful. The purpose of the present study was to find predictors of treatment success for comorbid anxiety disorders in alcohol-dependent patients. METHODS: The study was conducted in a sample of 34 completers with a double diagnosis of alcohol dependence and agoraphobia or social phobia who received CBT for their comorbid anxiety disorder in a 32-week randomized controlled trial comparing alcohol and CBT anxiety disorder treatment with alcohol treatment alone. In the current report, treatment success was defined as a clinically significant change (recovery) on the anxiety discomfort scale. RESULTS: The severity of comorbid alcohol dependence did not influence the beneficial effect of CBT on the anxiety disorder. Psychological distress (SCL 90), neuroticism (NEO N), conscientiousness (NEO C), gender, employment and age of onset of alcohol dependence showed some predictive value. CONCLUSIONS: Alcohol dependent males with a comorbid anxiety disorder seem to benefit most from CBT if their alcohol dependence started after age 25, if they are employed and if their general psychopathology is less severe. The most important conclusion, however, is that even severely alcohol-dependent patients with an anxiety disorder can benefit from psychotherapy for their anxiety disorder. PMID- 17356284 TI - Drug use patterns and drug-related disorders of cocaine users in a sample of the general population in Germany. AB - AIMS: The prevalence of cocaine use is still very low in Germany, but rates have been increasing over the past few decades. Patterns of drug consumption and related adverse consequences in individuals who have used cocaine were investigated in order to distinguish different types of cocaine users. METHODS: Data come from two national representative surveys on substance abuse in the German general population conducted in 1997 and 2000 using self- administered questionnaires. Overall response rates were 65 and 51%, respectively. The two samples were pooled (n = 16,159) and latent cluster analysis was conducted using a sub-sample of 272 lifetime cocaine users. RESULTS: Three clusters were derived: the majority belonged to the group of mainly unproblematic users (UPG, 80%), the second group comprised non-amphetamine poly-problem drug users (NAPPG, 12%), and a small group was composed of poly-problem drug users (PPG, 8%). Comparisons of sociodemographic characteristics, consumption patterns and age of onset for licit and illicit drug use revealed significant differences between the groups. CONCLUSIONS: The majority of cocaine users in the general population are experimental or occasional users of licit and illicit drugs. Rather than being a major drug, cocaine is one of many other licit and illicit drugs. Cocaine use as part of predominantly poly-drug use behaviour is strongly associated with substance-related disorders. PMID- 17356285 TI - Successful full-term twin pregnancy in hemoglobin Brockton: a rare hemoglobinopathy--case report. AB - INTRODUCTION: Hemoglobin Brockton is indicated by the hemolytic anemia, which is rare qualitative variant of aspect of the hemoglobinopathies. Hemoglobin disorders in pregnancy are associated intrauterine growth retardation, premature birth, and low birth weight. One of the unstable hemoglobinopathies, Hb Brockton associated with pregnancy has not been previously mentioned in the literature. In this case presentation and things to be done in case of a pregnant patient with rare hemoglobinopathy have been reviewed in reference to the literature. CASE REPORT: Twin pregnancy of a 26-year-old patient with Hb Brockton disorder which was diagnosed at the age of 11, and has led to minor hemolytic anemia crisis over the years, was observed. Due to decrease in hemoglobin level, 8 units of transfusion were made. A twin pregnancy continued without any problems until the 38th week when a caesarean section was performed due to breech-breech presentations. The hemoglobin pattern of the newborn was studied at birth and after 1 year; the variant in the mother was not found. DISCUSSION: During pregnancies with unstable hemoglobinopathy, observation of hemoglobin levels every 3 weeks and carrying out blood transfusions when below 8 g/dl can stabilize the pregnancy in terms of the development of the baby and the mother. Patients with hemoglobinopathy carry an increased risk for complications and should therefore seek medical care early in pregnancy and be managed by a multidisciplinary team of specialists. PMID- 17356286 TI - A case of heterotopic pregnancy in the absence of risk factors. A brief literature review. AB - OBJECTIVE: To reinforce the risk of heterotopic pregnancy in a natural cycle when intrauterine pregnancy and abdominal pain co-exist. METHOD: A single case report with a literature review. RESULTS: Our case was associated with significant haemorrhage, laparotomy and salpingectomy. The obstetric outcome was favourable in this case. The literature review demonstrates the diagnostic difficulties as well as treatment options. CONCLUSIONS: Sonographic diagnosis of a heterotopic pregnancy is not always possible. Patients with abdominal pain and intrauterine pregnancy should heighten the clinician's suspicion of a heterotopic pregnancy. PMID- 17356287 TI - Pregnancy on intensified hemodialysis: fetal surveillance and perinatal outcome. AB - OBJECTIVES: To evaluate the effect of intensive fetal surveillance via Doppler ultrasound and fetal non-stress test on the perinatal outcome of pregnant women undergoing an intensified hemofiltration scheme. METHODS: Five consecutive pregnancies of women undergoing intensified hemodialysis were analyzed due to the following parameters: maternal background, hemodialysis schedule during pregnancy, blood pressure, occurrence of fetal complications, occurrence of obstetric complications, gestational week at delivery, mode of delivery, and newborn outcome and follow-up. RESULTS: All pregnancies resulted in a live birth, mean gestational age was 32 weeks. Intrauterine growth restriction occurred in 4 fetuses, pathological umbilical artery flow velocity waveforms in 2. The mean birth weight was 1,764 g (range 1,274-2,465 g). Cesarean section was performed in 3 patients because of fetal distress. None of the patients developed severe complications like pre-eclampsia. CONCLUSIONS: Although intensified dialysis enables the maintenance of stable uteroplacental and fetal perfusion, intensive fetal monitoring is mandatory to reduce perinatal morbidity and mortality in pregnant women on maintenance dialysis. PMID- 17356288 TI - Age-related changes in intramyocellular lipid in humans by in vivo H-MR spectroscopy. AB - BACKGROUND: It is considered that the increasing intramyocellular lipid (IMCL) affects health risks and muscle attenuation. Though body fat increases significantly with age in lean humans, it is not known whether IMCL increases or not. In this study, we investigated the changes with age in IMCL concentrations in skeletal muscles using (1)H-MR spectroscopy and studied them in relation to body fat percentage, waist-hip ratio, and blood components. METHODS: Twenty-four lean young (age 21.2 +/- 1.9, BMI 21.5 +/- 1.8) and 23 lean old (age 70.9 +/- 2.4, BMI 21.7 +/- 1.3) subjects took part in the study. Subjects were grouped by gender into age- and BMI-matched young and old groups. The (1)H-MRS was obtained from the tibialis anterior (TA), medial gastrocnemius (MG) and soleus (SOL) muscles. RESULTS: The IMCL content in SOL and MG in the old was found to be higher (p < 0.01) than that in the young. No age difference in IMCL content in TA was found. IMCL concentrations in SOL were higher than those in MG and TA in the order of SOL > MG > TA (p < 0.01). IMCL content correlated significantly with waist-hip ratio in all skeletal muscles. A significant relationship was observed between percent body fat and IMCL in TA and MG (p < 0.05). However, no correlation was found between IMCL content in each muscle and BMI. The IMCL content in all skeletal muscles significantly correlated with HbA1c, triglyceride, total cholesterol and LDL cholesterol concentrations. CONCLUSION: These results suggest that increased IMCL in both lean older men and women might be related to body composition, blood lipids and lipoprotein profiles, and that this might affect muscle attenuation. PMID- 17356289 TI - Risk factors for aspiration pneumonia after percutaneous endoscopic gastrostomy. AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is generally used for long term enteral nutrition. Patients who require PEG placement are often very sick, and postoperative complications, especially aspiration pneumonia, can be fatal. OBJECTIVE: In this study we investigated the risk factors for aspiration pneumonia after PEG using a simple two-step swallowing provocation test (S-SPT), as reported in 1999 by Teramoto et al. METHODS: The study included 29 patients (10 men, 19 women; mean age 84.6 years) who underwent S-SPT before PEG. We evaluated the presence of reflux esophagitis (RE) and esophageal hiatal hernia (EHH) with PEG. According to the S-SPT results, a normal response to the 1st step S-SPT was given a score of 0, a normal response to the 2nd step S-SPT was given a score of 1, and an abnormal response to the 2nd step S-SPT was given a score of 3. In addition to S-SPT, the presence of RE was given a score of 3, the absence of RE was given a score of 0, the presence of EHH was given a score of 2, and the absence of EHH was given a score of 0. We evaluated the association between the presence of aspiration pneumonia, as an early and critical complication, up to 1 month after PEG and determined the total risk score (score of S-SPT+ score of RE+ score of EHH). RESULTS: The group with an abnormal response to the 2nd step S-SPT and the group with RE both exhibited aspiration pneumonia. The patients with aspiration pneumonia all achieved total scores > or =3, and 8 of 13 patients without aspiration pneumonia achieved scores < or =2. CONCLUSIONS: S-SPT is particularly useful in PEG patients. The scores provided by S-SPT and endoscopic examination can be very useful for aspiration pneumonia after PEG. The patients with scores < or =2 appear to be at very low risk for aspiration pneumonia, and patients with the scores > or =3 should be carefully followed up. PMID- 17356290 TI - rhGH treatment in corticosteroid-treated patients. AB - Children and adolescents treated for chronic diseases have non-specific metabolic abnormalities that lead to decreased growth velocity and abnormal body composition, including severe osteoporosis, muscle wasting and increased fat mass. Glucocorticoid (GC) therapy plays a major role in the complex pathogenesis of these metabolic abnormalities. Recombinant human growth hormone (rhGH) therapy was introduced a few years ago to reduce the severe disease- and GC-related metabolic consequences of juvenile idiopathic arthritis, other chronic diseases, and renal transplantation. Short- and mid-term rhGH treatment has consistently proved effective in overcoming GC-induced growth suppression, with a marked interindividual variability in the growth response to rhGH treatment. Safety of rhGH treatment, concerning the progression of the disease and glucose tolerance, was good. Prolonged follow-up until achievement of adult height is needed to better evaluate the impact of rhGH treatment on growth and body composition and the long-term consequences of hyperinsulinism. PMID- 17356291 TI - Infertility in cryptorchidism is linked to the stage of germ cell development at orchidopexy. AB - BACKGROUND: Cryptorchidism represents the most common endocrine disease in boys, with infertility frequently observed in unilateral as well as bilateral forms. In this study, we examined the role of Ad (dark) spermatogonia for fertility in cryptorchid boys. The hypothesis to be proven was that boys lacking Ad spermatogonia will develop infertility despite a successful orchidopexy at an early age. METHODS: To estimate total sperm count, one of the most predictive parameters of male fertility, we analyzed the ejaculatein 218 cryptorchid men and correlated it with the developmental stage of their germ cells at the time of successful surgery. RESULTS: Abnormal sperm concentration (<40 x 10(6)/ejaculate) was found in half of the patients under the study. 47.5% of unilateral and 78% of bilateral cryptorchid males had their sperm concentration in the infertility range according to the WHO standards. If transformation into Ad spermatogonia had occurred, age-related differences in the fertility outcome was observed. The younger the unilateral cryptorchid boys were at surgery, the higher their sperm count. Age-related difference was not found in the group of cryptorchid men having had no A dark spermatogonia at time of surgery, indicating that in this group a successful orchidopexy is insufficient to prevent infertility development and, in particular, the development of azoospermia. CONCLUSION: The presence of Ad spermatogonia at surgery is an excellent prognostic parameter for future fertility. Cryptorchid boys lacking these cells will develop infertility despite successful orchidopexy at an early age. PMID- 17356292 TI - Efficacy of a monthly compared to 3-monthly depot GnRH analogue (goserelin) in the treatment of children with central precocious puberty. AB - AIMS: To compare the efficacy of goserelin 10.8 mg (Zoladex LA-ZLA) administered 9-12 weekly with 3.6 mg (Zoladex-Z) given monthly in suppressing pubertal development, and effect on body mass index (BMI). METHODS: Children with central precocious puberty (CPP) treated with Z (n = 34) or ZLA (n = 28) were studied retrospectively. Pubertal scores and BMI SDS during 24 months' treatment were compared. RESULTS: To attain adequate pubertal suppression, more patients on ZLA than Z required increase in injection frequency (p = 0.02) and this was so for 7/8 patients with a structural aetiology for CPP on ZLA and 2/8 on Z. A greater proportion of patients on ZLA had BMI >+2 SDS before (p = 0.05), and at 18 and 24 months (p = 0.02 and 0.04). BMI SDS transiently increased during the first 6 months on ZLA (p = 0.04). CONCLUSION: Both Z and ZLA were effective in suppressing puberty. To achieve adequate suppression, increased injection frequency was more likely with ZLA than Z, and particularly in patients with structural defects. Children with CPP had an elevated BMI at the onset of therapy and ZLA had a transient positive influence on BMI. PMID- 17356293 TI - Incidence of obesity does not appear to be increased after treatment of acute lymphoblastic leukemia in Brazilian children: role of leptin, insulin, and IGF-1. AB - BACKGROUND/AIMS: It has been reported that children treated for acute lymphoblastic leukemia (ALL) in developed countries show an increased risk of overweight and obesity in adolescence and adulthood. However, the majority of patients who came to our observation in Brazil have low or normal body weight and only one of them was obese. Therefore, we have decided to assess some biochemical parameters possibly related to the intermediate metabolism and body composition in these patients. METHODS: Two groups of subjects were studied: 27 survivors of childhood ALL (14.0 +/- 4.2 years old; post-treatment interval 8.6 +/- 3.9 years) (ALL group) and 17 healthy subjects (12.8 +/- 4 years old) (control group) selected on the basis of their kinship with the patients. RESULTS: 14/27 patients of the ALL group and 4/17 of the control group had leptin levels higher than the normal range for age and sex (p < 0.05). The leptin level was significantly higher in the ALL group (15.5 +/- 1.8 ng/ml) than in the control group (10.7 +/- 2 ng/ml) (p < 0.05). When adjusted by sex, BMI z-score, and age, the level of leptin in patients of the ALL group was 8.5 higher than in subjects of the control group (p = 0.006). Leptin/insulin correlation in the ALL group was 0.08 and in the control group it was +0.585 (p < 0.05). CONCLUSION: The data indicate the presence of alterations in the homeostatic regulatory mechanisms controlling body weight in Brazilian patients treated for ALL in childhood, still, it did not lead to obesity in the absence of favorable environmental conditions. PMID- 17356294 TI - Growth hormone determination in children using an immunofunctional assay in comparison to conventional assays. AB - Conventional assays for determination of growth hormone (GH) in serum measure immunoreactive molecules of a blood sample. The immunofunctional assay (IFA), on the other hand, is able to determine biologically active molecules. In our study, we evaluated GH determination in children with IFA to compare these data with clinical reliable data of conventional assay systems, since there is only insufficient data concerning the clinical use of IFA in children. The comparison of GH determinations by IFA and two immunoradiometric assays showed different results for the same serum sample. Peak and trough concentration levels determined by these three different assays were always measured at the same time, but absolute GH concentration levels varied. Statistic analysis verified a linear regression of our data and allowed a conversion of data measured by IFA to predict values of the other assays used and vice versa. The traditional cut-off level for the diagnosis of GH deficiency of 10 ng/ml was based originally on results of polyclonal radioimmunoassays. This internationally applied cut-off level has been converted based on the regression analysis for prediction of this study and we found the 95% confidence interval on the mean measurements by IFA to be between 3.11 and 3.28 ng/ml. PMID- 17356295 TI - Thymus-derived CD4+ CD25+ T cells suppress the development of murine allergic conjunctivitis. AB - CD4+ CD25+ T cells regulate various kinds of immune-mediated diseases. Here, we sought to clarify whether CD4+ CD25+ T cells also regulate the development of experimental allergic conjunctivitis (EC). Thymectomized BALB/c mice, treated with anti-CD25 antibody (PC61), normal rat immunoglobulin G (nrIgG) or left untreated were immunized with short ragweed pollen (RW). Ten days later, the mice were challenged with RW in eye drops, and 24 h later, the conjunctivas, blood and spleens were harvested. The severity of EC, as evaluated by conjunctival eosinophil numbers, was significantly higher in the PC61-treated group as compared with the other two groups. The PC61-treated group also had significantly higher RW-specific IgE and IgG1 levels and displayed RW-specific splenocyte proliferation and RW-induced splenocyte T helper cell 2 cytokine production. However, PC61 treatment of unthymectomized mice did not affect the severity of EC. Thus, thymus-derived CD25+ T cells regulate the development of EC. Furthermore, transfer of Foxp3-expressing CD4+ CD25+ T cells from naive mice into RW-sensitized mice suppressed the development of EC in these mice after RW challenge. Taken together, these results suggest that CD4+ CD25+ T cells regulate the development of EC. PMID- 17356296 TI - Perceived food allergy in children in 10 European nations. A randomised telephone survey. AB - BACKGROUND: Food allergy is targeted as a public health priority by the European Union Commission. Parental perception of food allergy in their offspring is a proxy measure of the potential demand for allergy medicine services in the paediatric population. METHODS: A representative sample of the general population was contacted by a randomised telephone survey in Austria, Belgium, Denmark, Finland, Germany, Greece, Italy, Poland, Slovenia and Switzerland. A standardised questionnaire was administered regarding parentally perceived food allergy reports, symptoms, foods and medical service use by their live-in children. RESULTS: 40,246 adults were polled, yielding data on 8,825 children. Parentally perceived food allergy prevalence was 4.7% (90% CI 4.2-5.2%). The most affected age group was 2- to 3-year olds (7.2%). Single-country incidence ranged between 1.7% (Austria) to 11.7% (Finland). Milk (38.5%), fruits (29.5%), eggs (19.0%) and vegetables (13.5%) were most often implicated, although with significant age linked variations. Medical treatment was needed by 75.7% of affected children because of a food reaction. This translates into a proxy measure for food allergy prevalence of 3.75%. Skin symptoms were widespread (71.5%), followed by gastrointestinal (27.6%) and respiratory (18.5%) symptoms. DISCUSSION: We provide the first point prevalence of parentally perceived food allergy in the general paediatric population across the European Union. Parental reports confirm the public health significance of adverse reactions to some foods in specified age groups. Our data may inform intervention planning, cost of illness assessments and quality-of-life-enhancing public health measures. PMID- 17356297 TI - Recurrent anaphylaxis due to non-ruptured hepatic hydatid cysts. AB - BACKGROUND: Hydatid disease, a parasitic infestation of humans, is endemic in the Mediterranean region, Australia, New Zealand and the Middle East, and mostly involves the liver. Anaphylactic reactions, which sometimes are the first manifestations of the disease, frequently occur due to cyst rupture after a minor/major trauma, though they may also be spontaneously seen on rare occasions. In extremely few studies, anaphylactic shock has been reported in patients without macroscopic rupture of the hydatid cysts. CASE REPORT: Our patient had recurrent anaphylactic episodes without any trauma and had been misdiagnosed for several years even though the patient was living in a region endemic for hydatid disease. CONCLUSION: We emphasize that physicians should be highly aware of hydatid disease as a possible etiology for seemingly idiopathic anaphylactic reactions, especially in endemic regions. PMID- 17356298 TI - The role of endothelium-derived mediators in exercise-induced bronchoconstriction. AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition whose pathogenesis and effect on airways remain unclear. The aim of the study was to evaluate the changes in endothelial-derived mediators following intensive exercise in asthmatic patients. METHODS: The study was conducted in a group of 25 asthmatic patients (15 with EIB, 10 without EIB) and 8 healthy volunteers. Changes induced by intensive exercise in the plasma concentrations of endothelin-1 (ET-1), thrombomodulin and soluble E-selectin were determined. Moreover, the possible correlations of these measurements with the results of baseline lung function, bronchial hyperreactivity (BHR), exhaled nitric oxide (F(ENO)), baseline eosinophil cationic protein, peripheral blood eosinophilia and total IgE were investigated. RESULTS: In the group of asthmatics with EIB, statistically significantly higher baseline concentrations of ET-1 and soluble E selectin compared with asthmatics with negative exercise test results were revealed. In this group of patients, ET-1, thrombomodulin and soluble E-selectin concentrations significantly increased after exercise. Baseline concentrations of ET-1 as well as an increase in soluble E-selectin concentrations 60 min after exercise showed a statistically significant correlation with baseline eosinophil cationic protein, F(ENO) and BHR. The increase in plasma concentrations of ET-1 15 min after exercise and soluble E-selectin 60 min after exercise showed a statistically significant correlation with the increase in F(ENO) and BHR to histamine 24 h after exercise. CONCLUSIONS: We suggest that during EIB changes in the function of pulmonary endothelium occur and these changes may influence inflammation of the airway and remodeling in asthmatic patients. PMID- 17356299 TI - Human cytomegalovirus glycoprotein B genotype correlates with different symptoms of infected infants. AB - OBJECTIVES: Human cytomegalovirus (HCMV) is the pathogen of cytomegalic inclusion disease of infants. HCMV strains can be classified into four genotypes of glycoprotein B (gB). There are limited data concerning links between clinical symptoms and HCMV genotypes. The aims of the present study were to determine the genotype of HCMV isolates from pediatric patients who have different symptoms on the assumption that the gB genotype may influence the outcomes of congenital and prenatal HCMV infection. METHODS: The gB types of HCMV were determined in urine specimens from 208 infected infants using nested polymerase chain reaction and restriction fragment length polymorphism. RESULTS: These data showed the dominance of the gB1 genotype in HCMV-infected infants. The distributions of HCMV gB genotypes in jaundice, malformation, and pneumonia patients are different. CONCLUSION: There are some relationships between the gB genotypes and the different symptoms of HCMV infection. The four gB genotypes of HCMV may have different clinical outcomes in infected infants. PMID- 17356300 TI - HIV Tat protein increases Bcl-2 expression in monocytes which inhibits monocyte apoptosis induced by tumor necrosis factor-alpha-related apoptosis-induced ligand. AB - OBJECTIVE: To investigate the effect of HIV Tat protein on Bcl-2 expression in human monocytes, and observe apoptosis of Tat-stimulated monocytes induced by TNF alpha-related apoptosis-induced ligand (TRAIL). METHODS: Western blot was used to detect Bcl-2 expression in monocytes stimulated by HIV Tat protein, and Annexin V and 7-AAD staining were used to detect apoptosis of monocytes induced by TRAIL. RESULTS: HIV Tat protein increased Bcl-2 expression in human monocytes in a dose dependent manner. Annexin V staining showed that 51.54% of monocytes underwent apoptosis after being treated with 100 ng/ml recombinant TRAIL. When monocytes were prestimulated with HIV Tat, only 15.46% of monocytes underwent apoptosis. This effect can be inhibited by polyclonal anti-Tat serum. 7-AAD staining showed similar results. CONCLUSION: HIV Tat protein increases Bcl-2 expression in monocytes which inhibited apoptosis induced by TRAIL. HIV Tat protein may play an important role in the mechanisms of HIV-persistent infection in monocytes. PMID- 17356301 TI - Carboxyl-terminal sequence variation of latent membrane protein 1 gene in Epstein Barr virus-associated gastric carcinomas from Eastern China and Japan. AB - OBJECTIVES: To elucidate variations of latent membrane protein 1 (LMP1) in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and explore the LMP1 variations of neighboring countries, China and Japan. METHODS: In 12 and 8 EBVaGCs from eastern China and Japan, respectively, the C-termini of LMP1 were analyzed using PCR and sequencing. The sequences were compared with previously published strains and were characterized on a phylogenetic tree. The difference between Chinese and Japanese isolates was characterized. RESULTS: Ten of 12 Chinese GC isolates (83.3%) and all of the 8 (100%) Japanese GC isolates belonged to the China 1 strain. Also, B95-8 type isolates were found in 2 of 12 Chinese GC. In the 18 China 1 type isolates, additional mutations outside the signature sequence changes were found. All Japanese isolates (100%) had two or more additional mutations, whereas only 5 of 10 (50%) Chinese isolates had two or more additional mutations. The difference was statistically significant (p = 0.0359). CONCLUSIONS: China 1 is the dominant strain in GC from eastern China and Japan. The similarity to that of nasopharyngeal carcinoma (NPC) from China supports the view that China 1 strain represents a geographic-associated polymorphism rather than an NPC-associated polymorphism. Japanese isolates show more mutations than Chinese isolates, suggesting a geographic difference between Chinese and Japanese isolates in GC. PMID- 17356302 TI - Susceptibility of mouse macrophage J774 to dengue virus infection. AB - The aim of this study was to investigate whether the J774 mouse macrophage cell line could be used as an in vitro model for dengue virus infection (DENV). After 3 days, infection in J774 cells was assessed by detecting dengue virus non structural protein 1 (NSP-1) production either by dot blot or indirect immunofluorescence assay (IFA) of saponine-permeabilized J774 cells and then confirmed by RT-PCR (171 bp product, corresponding to the DENV-2 core). Based on the presence of NSP-1 in infected but not in non-infected cells by both IFA and dot blot, as well as the amplification of a 171-bp DENV-2-specific RT-PCR product exclusively in the infected cells, the J774 cell line was found to be permissive for dengue virus infection. As far as we know, this is the first report that the J774 mouse macrophage cell line is infected with dengue virus and, thus, that it can be used as an alternative in vitro model for dengue virus infection studies. This finding could help to further elucidate the mechanisms involved in dengue virus infection and pathogenesis. PMID- 17356303 TI - Inducible Cre/loxP recombination in the mouse proximal tubule. AB - Transgenic technologies in mice became invaluable experimental tools to identify the in vivo function of proteins. However, conventional knockout technology often results in embryonic lethality and because genes are frequently expressed in multiple cell types, the resulting knockout phenotypes can be complex and difficult or impossible to dissect. These issues are particularly important for gene-targeting strategies used to examine renal function. The kidney contains quite a number of different cell types, the function of many of which impacts that of other renal cells. To avoid these limitations conditional knockout strategies have been designed. As one important part of this system we describe the development of a mouse line expressing the tamoxifen-activatable Cre recombinase Cre-ER(T2) specifically in renal proximal tubules. The expression of Cre-ER(T2) is driven by a promoter fragment of the mouse gamma-glutamyl transpeptidase type II gene resulting in the generation of the activatable recombinase in S3 segments of the proximal tubules from which over 80% were positive for Cre activity. In combination with loxP-based conditional mutant mice as a second tool this tamoxifen-inducible Cre-ER(T2) line allows functional analysis of a variety of genes important for renal development and function in a precisely controlled spatiotemporal manner. PMID- 17356304 TI - Hair cortisol as a potential biologic marker of chronic stress in hospitalized neonates. AB - BACKGROUND: As preterm and term infants in the neonatal intensive care unit (NICU) undergo multiple stressful/painful procedures, research is required that addresses chronic stress. OBJECTIVES: To determine whether (a) hair cortisol levels differed between term and preterm infants exposed to stress in the NICU and (b) an association exists between hair cortisol levels and severity of illness or indicators of acute stress. METHODS: Hair cortisol levels were determined using the ELISA method (solid-phase enzyme-linked immunoassay, Alpco Diagnostics, Windham, N.H., USA) in 60 infants >25 weeks gestational age at birth. RESULTS: No significant differences were found between the hair cortisol levels of term infants compared to preterm infants in the NICU. When compared to a group of healthy term infants, hospitalized infants had significantly higher hair cortisol levels (t (76) = 2.755, p = 0.004). A subgroup analysis of the term NICU infants showed a statistically significant association between total number of ventilator days and hair cortisol levels. For every extra day on the ventilator, hair cortisol levels increased on average by 0.2 nmol/g (p = 0.03). 21% of the variance in hair cortisol levels was explained by the total number of days on the ventilator. CONCLUSIONS: Hair cortisol is influenced by days of ventilation in NICU term infants. This is a potentially valid outcome for chronic neonatal stress in these infants and warrants further investigation. PMID- 17356305 TI - Induction of early meconium evacuation promotes feeding tolerance in very low birth weight infants. AB - BACKGROUND: A delay in reaching full enteral feeding is linked to poorer outcome in preterm neonates. Meconium retention has been viewed as a cause of bowel dysfunction in very low birth weight infants (VLBWI). Thus, adequate evacuation of meconium could help to promote feeding tolerance. OBJECTIVES: Our goal was to determine the effect of the induction of early meconium evacuation on feeding tolerance in VLBWI. METHODS: An observational study involving two subsequent periods was performed in inborn infants with birth weights of <1,500 g, before (control) and after (study) the induction of early meconium evacuation by routine glycerin enema. The total duration of these periods was from January 2003 to December 2005. To evaluate feeding tolerance, we measured time to achieve full enteral feeding. Complications such as sepsis and necrotizing enterocolitis were compared. RESULTS: The study group achieved full enteral feeding significantly faster than the control group (hazard ratio (HR) = 2.9; 95% confidence interval (CI) = 1.8-4.8), and this effect was more definite in infants with a birth weight of <1,000 g (HR = 4.6; 95% CI = 1.9-11.1). The study group passed first meconium faster than the control group (median = 1.4 vs. 3.7 days; p < 0.001). Sepsis, especially as determined by positive culture in central venouscatheter, was significantly reduced in the study group (7.7 vs. 27.8%; p = 0.02). CONCLUSIONS: The induction of early meconium evacuation had a significantly positive effect on feeding tolerance and sepsis prevention in VLBWI. PMID- 17356306 TI - Association study between vesicle-associated membrane protein 2 gene polymorphisms and fluvoxamine response in Japanese major depressive patients. AB - BACKGROUND: Vesicle-associated membrane protein 2 (VAMP2) is a key component of the synaptic vesicle docking/fusion machinery and its mRNA reportedly increases in the frontal cortex of rats following chronic antidepressant and electroconvulsive treatment. VAMP2 is therefore thought to be involved in the mechanism of action of antidepressants and may alter their efficacy. The purpose of this study was to investigate whether the VAMP2 gene is associated with clinical responses to a specific antidepressant, fluvoxamine. METHODS: A total of 106 patients with major depressive disorder were given fluvoxamine (50-200 mg/day) for 8 weeks and assessed for severity of depression using the Semi Structured Interview Guide of the Hamilton Depressive Scale (SIGH-D; 17 items) at 0 and 8 weeks. We defined a clinical response as more than a 50% reduction in baseline SIGH-D within 8 weeks, and defined clinical remission as a SIGH-D score of less than 7 at 8 weeks. Genotyping was performed by PCR-RFLP. RESULTS: Analysis of haplotype tagging single nucleotide polymorphisms as well as haplotype analysis did not reveal any significant associations. CONCLUSION: Our results suggest that the VAMP2 gene is unlikely to play a major role in the efficacy of fluvoxamine. PMID- 17356307 TI - Neuropsychobiological evidence for the functional presence and expression of cannabinoid CB2 receptors in the brain. AB - For over a decade, until recently, it was thought that marijuana acts by activating brain-type cannabinoid receptors called CB1, and that a second type called CB2 cannabinoid receptor was found only in peripheral tissues. Neuronal CB2 receptors in the brain had been controversial. We reported the discovery and functional presence of CB2 cannabinoid receptors in the mammalian brain that may be involved in depression and drug abuse and this was supported by reports of identification of neuronal CB2 receptors that are involved in emesis. RT-PCR, immunoblotting, hippocampal cultures, immunohistochemistry, transmission electron microscopy, and stereotaxic techniques with behavioral assays were used to determine the functional expression of CB2 cannabinoid receptors in the rat brain and mouse brain exposed to chronic mild stress or treated with abused drugs. RT PCR analyses supported the expression of brain CB2 receptor transcripts at levels much lower than those of CB1 receptors. In situ hybridization revealed CB2 mRNA in cerebellar neurons of wild-type but not of CB2 knockout mice. Abundant CB2 receptor immunoreactivity (iCB2) in neuronal and glial processes was detected in the brain. The effect of direct CB2 antisense oligonucleotide injection into the brain and treatment with JWH015 in motor function and plus-maze tests also demonstrated the functional presence of CB2 cannabinoid receptors in the central nervous system. In humans, there was a high incidence of Q63R polymorphism in the CB2 gene in Japanese alcoholics and depressed subjects. Contrary to the prevailing view that CB2 cannabinoid receptors are restricted to peripheral tissues and predominantly in immune cells, we demonstrated that CB2 cannabinoid receptors and their gene transcripts are widely distributed in the brain. This multifocal expression of iCB2 in the brain suggests that CB2 receptors may play broader roles than previously anticipated and may therefore be exploited as new targets in the treatment of depression and substance abuse. PMID- 17356308 TI - Amisulpride versus risperidone treatment for behavioral and psychological symptoms in patients with dementia of the Alzheimer type: a randomized, open, prospective study. AB - The aim of this study was to evaluate the effectiveness and tolerability of both amisulpride and risperidone for treating the behavioral and psychological symptoms of dementia in patients with dementia of the Alzheimer type (DAT). Twenty-eight patients with DAT were randomly assigned to treatment with either amisulpride or risperidone for 8 weeks. The effectiveness of the treatments was assessed with the Neuropsychiatric Inventory (NPI) and the Clinical Global Impression-Severity of Illness (CGI-S) scale. The Simpson-Angus Rating Scale, the Barnes Akathisia Rating Scale and the Abnormal Involuntary Movement Scale were used for the assessment of side effects. The NPI and CGI-S scores were significantly decreased over time in both treatment groups without any significant group difference and time by treatment group interaction effect (F=71.85, p<0.0001). There were no serious adverse events in both groups. This study showed that either amisulpride or risperidone would be effective and tolerable for treating patients with DAT. Adequately powered studies with a head to-head comparison design will be mandatory to draw any definite conclusion. PMID- 17356309 TI - Hydroxyl radical mediates the augmented angiotensin II responses in thoracic aorta of spontaneously hypertensive rats. AB - AIM: To investigate the role of hydroxyl radical in augmented angiotensin II (Ang II) responses in the thoracic aorta of spontaneously hypertensive rats (SHR). METHODS: To elucidate the role of hydroxyl radical, we used edaravone (3-methyl-1 phenyl-2-pyrazolin-5-one) as a tool for our study. The vascular responses to Ang II (10(-10) to 10(-6) mol/l), tert-butyl hydroperoxide (tBHP; 10(-6) to 10(-2) mol/l) and H(2)O(2) (10(-6) to 10(-2) mol/l) were constructed in aortic preparations obtained from control (WKY) and SHR in the absence and presence of edaravone. RESULTS: The vascular responses to Ang II, tBHP and H(2)O(2) were found to be enhanced in aortic preparations from SHR as compared to control WKY rats. Edaravone selectively attenuated the augmented responses to Ang II but not to tBHP and H(2)O(2) suggesting that the .OH radical is involved in the augmented responses to Ang II. The elevated blood pressure in SHR was restored to a near normal value after 2 weeks of edaravone (10 mg kg(-1) i.p., b.i.d.) treatment. CONCLUSION: From the results we infer that hydroxyl radical stress augments Ang II responses in the thoracic aorta of SHR and, by attenuating these enhanced vascular responses, edaravone could serve as an adjuvant antioxidant therapy for the vascular complications of hypertension. PMID- 17356310 TI - Effect of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on ischemia-reperfusion injury in rats. AB - Two groups of rats were used to examine the effect of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, on rat hearts using an in vivo model of ischemia-reperfusion (I/R) to elucidate potential mechanisms. One group was the 30-min reperfusion group, which was further subdivided into sham (n=5), vehicle (n=6) and pioglitazone (3 mg x kg(-1), n=7) treatment groups with 30 min ischemia followed by 30 min reperfusion to detect data related to cardiac function and the area of myocardial infarction. The other group was the 120-min reperfusion group, subdivided into sham (n=5), vehicle (n=6), and pioglitazone 0.3 mg x kg(-1) (n=6), 1 mg x kg(-1) (n=7) and 3 mg x kg(-1) (n=6) treatment groups. Immunohistochemistry, in situ hybridization, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and DNA agarose gel electrophoresis were performed to detect apoptosis and expressions of Bax, Bcl-2, caspase 3, MMP-2 and PPARgamma protein, and MMP-2 and PPARgamma mRNA. We found that, after acute treatment with pioglitazone, the ratio of necrosis to area at risk decreased by 28% (p<0.01) and that of necrosis to left ventricle was reduced by 32% (p<0.01), compared with the vehicle group. Heart rate and +dp/dt(max), representing the cardiac systolic function, as well as -dp/dt(max), the indicator of cardiac diastolic function, improved significantly at 1 and 30 min after reperfusion (p<0.05-0.01). Furthermore, myocardial apoptosis was significantly suppressed by acute treatment with pioglitazone as evidenced by the decreased number of TUNEL-positive myocytes and DNA ladder, enhanced Bcl-2 protein expression, reduced Bax and caspase 3 protein expression in a dose-dependent manner compared with vehicle-treated rats. In addition, acute treatment with pioglitazone dose-dependently increased PPARgamma expression and decreased MMP-2 expression at protein and mRNA levels. Our findings demonstrate that a PPARgamma agonist may protect the heart from I/R injury. The protective effect is likely to occur by reducing cardiomyocyte apoptosis and inhibiting MMP-2. PMID- 17356311 TI - The biochemical analysis of methadone modulation on morphine-induced tolerance and dependence in the rat brain. AB - We have recently demonstrated that the combination of methadone and morphine enhances the ability of morphine to induce mu-opioid peptide (MOP) receptor endocytosis. As a result, rats receiving both drugs show reduced morphine tolerance and dependence. In the present study, we identify the biochemical basis for the protective effect of the drug combination. In rats treated with morphine alone, the inhibitory effect of DAMGO on forskolin-stimulated adenylyl cyclase activity was significantly reduced in a brain-region-selective manner. Importantly, these reductions were prevented in animals receiving the drug combination. We found that these changes were not due to alterations in MOP receptor density, or MOP receptor-G protein coupling, as no significant change in these parameters was observed. Together these data demonstrate that neither changes in receptor number nor function are required for morphine tolerance and dependence. Rather, brain-region-selective changes in adenylyl cyclase signal transduction are critical, and both these biochemical changes and the behavioral effects are prevented by facilitating endocytosis of the MOP receptor. PMID- 17356312 TI - Primary Sjogren's syndrome presenting as hypokalemic paralysis. PMID- 17356313 TI - Rapid detection of clarithromycin-resistant Helicobacter pylori in patients with dyspepsia by fluorescent in situ hybridization (FISH) compared with the E-test. AB - BACKGROUND: Clarithromycin is the antibiotic of choice for treatment of H.pylori related dyspepsia, but unfortunately, resistance to clarithromycin is not rare. Detection of resistant strains takes 2 to 4 days by conventional methods. In this report, we applied the FISH technique for rapid detection of H.pylori in biopsies of dyspeptic patients. METHODS: Gastric biopsies from 50 patients suffering from dyspepsia were tested in this study. Part of each biopsy specimen was cultured and the remainder was fixed in liquid nitrogen. After mounting of frozen sections on microscopic slides, they were hybridized with oligonucleotide probes for detection of clarithromycin-resistant H.pylori. The slides were visualized under a fluorescent microscope. Susceptibility of cultured strains of H. pylori to clarithromycin was also determined by the E-test and the results were compared. RESULTS: Twenty-five of 50 biopsy specimens examined by FISH were positive for H.pylori. FISH showed that 17 strains (68%) were susceptible to clarithromycin and 6 strains (24%) were resistant. Bacteria isolated following culture of 2 biopsy specimens had a mixture of both clarithromycin-susceptible and resistant strains (8%). There was no discrepancy between the E-test and FISH technique for detection of resistant strains of H.pylori. CONCLUSION: FISH is a rapid technique for detection of H.pylori in clinical samples. Moreover, strains susceptible to clarithromycin can be detected quickly. Therefore, this method is suitable for determination of susceptibility of H.pylori to clarithromycin, especially when a quick decision is necessary for treating dyspeptic patients. PMID- 17356314 TI - Pachygyria in a neonate with trisomy 21. PMID- 17356315 TI - Diagnosis: intralobar sequestration. PMID- 17356316 TI - Causes of admission to intensive care units in the Hajj period of the Islamic year 1424 (2004). AB - BACKGROUND: Approximately 2 to 3 million pilgrims perform Hajj every year. We describe the pattern of diseases, complications, and outcome of pilgrims who required admission to intensive care units (ICUs) during the Hajj period of the Islamic year 1424 (2004). METHODS: This was a cross-sectional study of all patients admitted to 104 ICU beds in four hospitals in Mena and three hospitals in Arafat during the Hajj. RESULTS: Of 140 patients admitted to ICUs, 75 (54%) patients were older than 60 years. The risk of complications and death increased with age, with the highest risk noticed among pilgrims older than 80 years. Ninety-four (67.6%) patients were men. Eighty-nine (63.6%) patients were admitted with cardiovascular diseases and 37 (26.4%) patients with infections. Myocardial infarction (25%) and pneumonia (22%) were the most common admitting diagnoses. Trauma accounted for only 6.4% (9 patients) of admissions. Sixty-three (45.0%) patients recovered and were discharged or transferred to hospital wards in stable condition, 40 (28.6%) were transferred to tertiary care centers for specialized services, 21 (15.0%) were transferred to tertiary care centers after closure of the temporary hospitals in Mena and Arafat, 15 (10.7%) patients died, and one (0.7%) patient was ddischarged against medical advice. CONCLUSION: This study revealed information oo the pattern of diseases and the most common causes of admission of pilgrims to ICUs and the required medical services during Hajj. It is hoped that this information will be of help to health care planners and officials to provide optimal and cost effective health care services to pilgrims in Hajj. PMID- 17356318 TI - Live Ascaris lumbricoides in the peritoneal cavity. PMID- 17356317 TI - Comparison of six-minute walking tests conducted with and without supplemental oxygen in patients with chronic obstructive pulmonary disease and exercise induced oxygen desaturation. AB - BACKGROUND: There are contradictory reports in the literature on the effects of supplemental oxygen administered before or after exercise tests. In light of this, we compared the results of 6-minute walking tests performed in room-air conditions (A6MWT) and with supplemental oxygen (O6MWT) in patients with chronic obstructive pulmonary disease (COPD) and exercise-induced oxygen desaturation. PATIENTS AND METHODS: Thirty-one patients with COPD were included in the study. The A6MWT and O6MWT were performed in randomized order on each patient. During the tests, severity of dyspnea and tiring of the leg were evaluated by the Modified Borg Scale. Heart rate and pulsed oxygen saturation and blood pressure were measured by pulse oximeter. RESULTS: Walking distance was longer with the O6MWT than with the A6MWT (P=0.001). The O6MWT resulted in a smaller increase in dyspnea, leg fatigue, and heart rate and a smaller drop in pulsed saturation than the A6MWT (P<0.05). The walking distance with the O6MWT correlated with respiratory function and hemodynamic parameters (P<0.05). CONCLUSION: The O6MWT, which produced less hemodynamic stress and was safer than the A6MWT, might provide more accurate information on exercise limitation for patients with COPD. These results suggest that the O6MWT can be used as a standard walking exercise test for patients with COPD and exercise-induced oxygen desaturation. PMID- 17356319 TI - Congenital pouch colon syndrome: a report of 17 cases. AB - BACKGROUND: Congenital pouch syndrome (CPC) is a rare condition seen in association with anorectal malformation that occurs almost exclusively in northern India. We reviewed cases seen in our institution to study aspects of clinical presentation, diagnosis, embryogenesis and management and raise awareness of this relatively infrequent entity. PATIENTS AND METHODS: From March 2002 to September 2004, 17 neonates/infants (11 males and 6 females) treated for CPC associated with anorectal malformations included 13 with type IV and 4 with type I CPC. Diagnosis was made by a single large air-fluid level on the infantogram occupying more than 50% of the entire abdominal dimension. RESULTS: In all patients, the pouch had fistulous communication with the genitourinary system, and there were other associated anomalies as well. Of 13 patients with pouch colon type IV, 11 neonates underwent laparotomy, ligation of the fistula, excision of the colonic pouch and end colostomy as a stage 1 procedure. Subsequently, these patients underwent definitive surgery, i.e. abdominoperineal posterior sagittal anorectoplasty (AP-PSARP), with or without covering colostomy. Two of 4 patients with type 1 CPC underwent laparotomy, ligation of the fistula and colorrhaphy as a first-stage operation before AP-PSARP. In our series, 4 patients were diagnosed intraoperatively and were treated in accordance with their operative findings. Post-operatively, there were no major complications except wound infection in some patients. There was one death that was not related to surgery. CONCLUSION: There are variants of the anomaly, but the possibility of CPC needs to be kept in mind as a possible association with anorectal malformations. PMID- 17356320 TI - Validation of three noninvasive laboratory variables to predict significant fibrosis and cirrhosis in patients with chronic hepatitis C in Saudi Arabia. AB - BACKGROUND: We tested the clinical utility of the platelet count, the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the AST to platelet ratio index (APRI) score in predicting the presence or absence of advanced fibrosis and cirrhosis in patients with chronic hepatitis C in Saudi Arabia. METHODS: Liver biopsy procedures performed on chronic hepatitis C patients in our gastroenterology unit at King Khalid University Hospital were traced from records between the years 1998 to 2003. The hospital computer database was then accessed and detailed laboratory parameters obtained. By plotting receiver operating characteristic curves (ROC), three selected models (platelet count, AST/ALT ratio, and the APRI score was the one associated with the highest area under the curve (AUC)=0.812 (95% CI, 0.756-0.868) on the ROC curves, compared to the platelet count and AST/ALT ratio, which yielded an AUC of 0.783 (0.711-0.855) and 0.716 (0.642-0.789), respectively. CONCLUSION: The APRI score seemed to be the best predictive variable for the presence or absence of advanced fibrosis in Saudi hepatitis C patients. PMID- 17356321 TI - Profile of major congenital anomalies in the Dhahira region, Oman. PMID- 17356322 TI - Revision hip arthroplasty in sickle cell disease. PMID- 17356323 TI - Relative contribution of digital rectal examination and transrectal ultrasonography in interpreting serum prostate-specific antigen values for screening prostate cancer in Arab men. AB - BACKGROUND: This study was conducted to determine the utility of digital rectal examination (DRE), transrectal ultrasonography (TRUS) and serum prostate-specific antigen (PSA) in the diagnosis of prostate cancer in men in Arabia, an are of the world with a relatively low incidence of this disease. PATIENTS AND METHODS: 329 patients suspected of having prostate cancer on account of raised serum PSA level (>4 ng/ml), DRE or TRUS findings, underwent TRUS-guided prostate biopsy. Raised PSA individually as well as combined, or a lesion suspicious of carcinoma on DRE or TRUS was recorded as PSA(+), DRE(+) or TRUS(+), respectively. The contribution of DRE, TRUS and serum PSA to the diagnosis of prostate cancer was analysed. RESULTS: Of the 329 patients who had prostate biopsies 109 cases (33.1%) had PCa. Of these 109 patients 56 (51%) had DRE(+), 77 (42%) had TRUS(+) and 49 (66%) had both DRE(+) and TRUS(+). Statistical analysis revealed that DRE(+) tripled the probability for cancer. PSA over a range of 10-50 ng/mL demonstrated an increasing cancer probability ranging from 2 to 3 fold. TRUS(+) was only significantly associated with cancer risk if PSA was elevated. The presence of all three factors increased the cancer probability by 6 to 7 fold. CONCLUSION: TRUS findings are dependent on PSA for interpretation while DRE(+) with elevated PSA makes PCa more likely. PMID- 17356324 TI - A tribute to Harriet Helen Werley. PMID- 17356327 TI - Nurses' evaluations of a novel design for an electronic medication administration record. AB - An electronic medication administration record is at the intersection of several disciplines: medicine, nursing, pharmacy, and allied health; however, it is the centerpiece of nurses' work for medication administration in acute care settings. Despite the crucial nature of the electronic medication administration record, human-computer interaction and health literature are silent about design recommendations and evaluations for such records. This study determined critical on-line medication management tasks for acute care nurses through videotaped, semistructured interviews with nurses and then observations of nurses during medication administration tasks. Subsequently, a novel electronic medication administration record prototype was developed and evaluated. The usability evaluation of this new record was positive based upon scores from the Questionnaire for User Interaction Satisfaction and comments about the display. Mean scores for this questionnaire averaged 7.2 to 7.9 (on a scale of 1-9) or from 80.2% to 87.8%. Accuracy scores were low for tasks requiring nurses to examine data outside the immediate field of view. Specific design recommendations are made to alleviate accuracy errors for specific tasks in acute care settings. PMID- 17356328 TI - The impact of a PDA-assisted documentation tutorial on student nurses' attitudes. AB - The purpose of this pretest-posttest study was to determine the effect of a PDA assisted documentation tutorial on fourth-year student nurses' (n=56) attitudes toward computerized documentation, anticipation to exercise of professional judgment when documenting, and satisfaction with computer technology for documentation. Paired t test showed significant increases in anticipation to use professional nursing judgment and satisfaction with the PDA for documentation. Satisfaction with the PDA for documentation was positively and significantly related to attitudes toward computerized documentation (r=.46, P<.01), and satisfaction with a PDA learning tutorial (r=.46, P<.01). Attitudes toward computerized documentation, length of nursing experience, and satisfaction with the PDA learning tutorial predicted satisfaction with the PDA for documentation. Seventy percent of 213 comments about the value of the PDA were favorable. These findings indicate that the PDA may be a valuable documentation tool for teaching professional nursing judgment and documentation skills to undergraduate nursing students. PMID- 17356330 TI - Medication bar coding: to scan or not to scan? AB - Practical steps for implementing a medication verification system using bar coding are provided. The authors describe the process that a two-hospital system embarked upon to implement a bedside medication verification system. Building blocks of the system are described that made the project successful and met the Patient Safety Goals of the Joint Commission on Accreditation of Healthcare Organizations. The authors identify the "pitfalls" organizations need to be prepared to handle and quantify financial and safety results achieved with this project. PMID- 17356331 TI - The children's computerized physical activity reporter: children as partners in the design and usability evaluation of an application for self-reporting physical activity. AB - The objectives of this three-phased study were to design and evaluate the usability of a computerized questionnaire, The Children's Computerized Physical Activity Reporter, designed with and for middle school children's self-report of physical activity. Study design was qualitative, descriptive, and collaborative, framed in a usability engineering model, with 22 participating children (grades 6 8; mean age, 12.5 years; range, 11-15 years) of three ethnic backgrounds. In Phase 1, children's understanding of physical activity and needs for reporting were determined, which were then translated in Phase 2 to the design features and content of the questionnaire; content validity, readability, and algorithm reliability were completed. Phase 3 involved children's evaluation of the questionnaire's usability (ease of use, efficiency, and aesthetics). The children all liked the questionnaire but identified several usability issues within instructions and reports. Working collaboratively with children was highly effective in ascertaining their understanding of physical activity and their self reporting needs. Thus, the questionnaire's design was created from children's understanding of physical activity and their needs for recalling activities. The development of the questionnaire and its usability evaluation contribute to understanding children's physical activity and to the importance of designing for usability. Additional research is needed to ascertain reliability and validity of data derived from its use and to explore its usefulness in clinical or research venues. PMID- 17356332 TI - Patients' perceptions of nurses' bedside use of PDAs. AB - Despite emerging interest in PDA use in healthcare, few studies have explored patients' perceptions of this technology being incorporated into their care. The purpose of this study was to explore patients' perceptions of nurses' bedside use of PDAs. This descriptive, exploratory qualitative study used one-on-one, in depth interviews to collect data from 14 patients at a medical center in Taiwan. Interview data were analyzed according to Miles and Hubermans' data reduction, data display, and conclusion verification process. The results indicate that patients perceived that PDA use could increase nurses' efficiency in data retrieval and calculation, were concerned about data accuracy and privacy, preferred that nurses explain the reasons for PDA use, suggested more functions for PDAs (eg, entertainment for pediatric patients, wireless paging for clinicians), and valued nursing care over technology use. These results can be used as a reference for clinicians implementing a point-of-care technology for patient care. PMID- 17356333 TI - Patient first: a patient sensitivity tool for an electronic health record implementation. AB - Throughout the country, use of electronic health records continues to increase. For successful implementation of an electronic health record system in an acute care setting, it is vital to educate and address the patient's perceptions about the use of technology when caring for the patient. This article describes the development of an educational sensitivity tool designed to enhance clinicians' simultaneous interactions with patients and computers in a midsize community hospital. The Patient First tool brings attention to the thoughts and perceptions a patient may have in various situations, promoting alternative solutions for staff to properly address the patient's concerns. A committee was developed to address concerns regarding the impact a computer at the bedside would have on patient and clinician interactions. One primary educational tool developed was the Patient First sensitivity presentation that cautioned and guided clinicians to be aware of patient perceptions. PMID- 17356336 TI - Neuropsychologic assessment of patients with advanced Parkinson disease submitted to extradural motor cortex stimulation. AB - OBJECTIVE: The aim of this study was to evaluate changes in cognitive functioning and emotive state in 3 inpatients with advanced Parkinson disease (PD) treated with extradural motor cortex stimulation (EMCS), an experimental neurosurgical procedure. BACKGROUND: Studies on the neuropsychologic assessment of patients with PD after EMCS are in process. The procedure has been applied for some years as an experimental method for treating PD. METHOD: A battery of neuropsychologic tests and emotive assessment scales were administered to 3 inpatients with PD 2 days before the intervention and then again after 1 year to evaluate changes in cognitive functioning and emotive state. RESULTS: At 1-year postintervention, cognitive functions and depressive symptoms were steady; 2 patients showed a mild improvement in quality of life. CONCLUSIONS: In this patient group, EMCS, an experimental neurosurgical treatment, had a positive effect on motor symptoms. Neuropsychologic assessment after a 1-year follow-up period showed that cognitive functions had not changed with respect to baseline characteristics. PMID- 17356337 TI - Artwork before and after onset of progressive nonfluent aphasia. AB - OBJECTIVE: Compare changes in art quality before and after the onset of progressive nonfluent aphasia (PA). BACKGROUND: Some patients with left frontotemporal lobar degeneration (FTLD), particularly PA start painting and improve in art despite their disease. There is only 1 case reported of FTLD where the person was an artist before onset. METHODS: Digital images of 7 paintings were obtained. Three paintings were from 6 years before onset of PA, 1 was from year of onset, and 3 were from 5 years after. Seven college-educated raters without art backgrounds, 5 men and 2 women, used a 1 to 5 point scale to rate 4 qualities of the paintings: representation, esthetics, novelty, and closure. The subjects had not previously viewed these paintings. One art expert also rated the paintings on these 4 qualities. RESULTS: Quality ratings did not differ for 3 qualities, but novelty decreased over time. The art expert rated all qualities stable over time. CONCLUSIONS: Artistic ability in this previously trained artist with PA did not improve. Instead, the novelty of her work decreased. FTLD may not improve artistic skills in those who already possess them and there can be a decrease in one quality strongly related to creativity-novelty. PMID- 17356338 TI - Treatment of juvenile Parkinson disease and the recurrent emergence of pathologic gambling. AB - OBJECTIVE: To describe the recurrent emergence of pathologic gambling (PG) during the sequential treatment of a patient with Juvenile Parkinson disease (PD) with different dopamine agonists. METHOD: Single case report. RESULTS: A patient with Juvenile PD developed PG soon after beginning treatment with pergolide, a mixed D1/D2 dopamine agonist that is also supposed to exhibit D3 activity. This behavior remitted upon the discontinuation of the drug. A subsequent therapeutic trial with pramipexole, a dopamine agonist with preferential D3 dopamine receptor activity, resulted in the recurrence of PG. Remarkably, previous treatment with levodopa was not associated with this side effect. CONCLUSIONS: These findings seem to confirm previous suggestions that dopaminergic hyperactivity plays an important role in the pathogenesis of PG. They further indicate that patients with PD may develop PG as a side effect of more than one dopamine agonist. There is still no consensus regarding the best strategy to deal with this potentially disturbing phenomenon. PMID- 17356339 TI - A case of progressive apraxia of speech in pathologically verified Alzheimer disease. AB - OBJECTIVE: To present the case of a man with progressive speech loss and other clinical features and diagnostic tests consistent with fronto-temporal dementia but whose postmortem neuropathologic findings revealed Alzheimer disease (AD). BACKGROUND: Progressive apraxia of speech presents without true language abnormalities, usually seen with frontal lesions and not associated with AD pathology. METHOD: We describe the clinico-pathologic case of an 87-year-old man with progressive loss of speech function and present the prospective presentation of his syndrome using structural (magnetic resonance imaging) and metabolic (positron emission tomography) neuro-imaging studies, neuropsychologic testing, and pathology. RESULTS: His syndrome was characterized over the first 6 to 9 years by progressive deterioration of speech production, alteration of mood, and dysphagia but near normal language, memory, and visual-spatial function. At 8 years, fluorodeoxyglucose-positron emission tomography showed largely frontal metabolic abnormality. Over his final 1(1/2) years, he was mute and withdrawn. Neuropathologic findings showed neuritic plaques and neurofibrillary tangles, but no signs of frontotemporal dementias such as Pick bodies or ubiquitinated tau negative inclusions. CONCLUSIONS: There can be overlap in the presentation of fronto-temporal dementia and AD despite the disparate pathologic bases of the underlying diseases. It has yet to be determined how to differentiate these diseases in such variant presentations and whether such atypical AD syndromes are equally amenable to standard therapies for AD. PMID- 17356340 TI - Catatonia in obsessive-compulsive disorder: etiopathogenesis, differential diagnosis, and clinical management. AB - OBJECTIVE: We describe the case of a patient who developed an episode of catatonia during the course of her life-long obsessive-compulsive disorder (OCD) and discuss issues related to the etiopathogenesis, differential diagnosis, and therapeutic management of this association. BACKGROUND: Catatonia is conventionally considered a heterogeneous syndrome of motor dysregulation characterized by mutism, immobility, negativism, posturing (catalepsy), stereotypies, and echophenomena. The relationship between OCD and catatonia is still misunderstood and poses significant challenges to the diagnosis and treatment of patients with both conditions. METHOD: Naturalistic follow-up of a single case. RESULTS: A patient with OCD developed catatonia in concert with deteriorating mood, thought, and behavior. This atypical clinical presentation of individuals with OCD and the list of differential diagnosis raised during the patient's clinical assessment are discussed on 3 different levels: symptomatic presentation, comorbidity pattern, and pharmacodynamic mechanisms involved. CONCLUSIONS: The development of a systematic therapeutic plan for patients with OCD and comorbid catatonia includes: the fine-tuning of the antiobsessional treatment; management of comorbid disorders that may engender catatonia; prompt discontinuation, and subsequent slow reintroduction of drugs deemed to trigger toxic reactions or to worsen comorbid disorders and, ultimately, the catatonia; and the implementation of specific anticatatonia measures. PMID- 17356341 TI - Neural networks essential for naming and word comprehension. AB - Lesion/deficit association studies of aphasia commonly focus on one brain region as primarily responsible for a particular language deficit. However, functional imaging and some lesion studies indicate that multiple brain regions are likely necessary for any language task. We tested 156 acute stroke patients on basic language tasks (naming and spoken and written word comprehension) and magnetic resonance diffusion and perfusion imaging to determine the relative contributions of various brain regions to each task. Multivariate linear regression analysis indicated that the error rate on each task was best predicted by dysfunction in several perisylvian regions, with both common and distinct regions for the 3 tasks. PMID- 17356342 TI - C-reactive protein and cognitive deficits in systemic lupus erythematosus. AB - OBJECTIVE: Recent studies have highlighted the role of serum C-reactive protein (CRP) as a marker for atherosclerosis, and a predictor for vascular disease and stroke. Systemic lupus erythematosus (SLE) has been associated with (1) higher levels of CRP, (2) cerebrovascular disease, and (3) a "subcortical" pattern of cognitive deficits (eg, lower processing speed, poor working memory). These findings suggest that microvascular changes affect cognition in SLE. To our knowledge, no studies have yet attempted to relate levels of CRP with cognitive deficits in SLE. In the present study, we investigated the relationship between CRP level and measures of working memory/processing speed in SLE. METHODS: The Paced Auditory Serial Addition Test (PASAT), a sensitive measure of processing speed and working memory, was administered as part of a full neuropsychologic battery. CRP levels were obtained from blood collected on the day of cognitive testing. SLE patients were divided into 2 groups: No detectable CRP (No-CRP) and detectable CRP levels (Elevated-CRP). RESULTS: In comparison to the No-CRP group, the Elevated-CRP group performed more poorly on the PASAT. They had fewer correct responses, fewer consecutive correct responses (dyads), and a greater percentage of responses that were obtained by using a less demanding but incorrect "chunking" strategy to perform the PASAT. CONCLUSIONS: Results suggest that CRP may be a sensitive marker for subtle executive dysfunction in SLE, possibly due to central nervous system microvascular autoimmune processes. Early treatment of vasculopathy in SLE may help prevent microvascular disease and associated cognitive dysfunction. PMID- 17356343 TI - Primary progressive aphasia: relationship between gender and severity of language impairment. AB - BACKGROUND/AIMS: Factors influencing the course and severity of symptoms in primary progressive aphasia (PPA), a language-based dementia, have not been fully elucidated. The current study examined the influence of gender on performance on tests of naming and verbal fluency in patients with PPA. Comparisons were also made within a group of probable Alzheimer disease (AD) patients to determine whether gender differences were present in the most common form of neurodegenerative dementia. METHODS: Performance was compared by gender within each diagnostic group on 3 language measures: the Boston Naming Test, category fluency (animals), and lexical fluency (FAS). Scores were compared at baseline (Visit 1) and in a subset of participants 6 to 15 months later (Visit 2). RESULTS: Compared to men, women with PPA demonstrated significantly greater impairment on word fluency tests at both visits and also had a more aggressive rate of decline between visits. AD patients showed no differences by gender on any measure. CONCLUSIONS: The results suggest gender-based vulnerability in PPA where women express more severe language impairments than men given a similar duration of illness. PMID- 17356344 TI - Problem solving ability in patients with mild cognitive impairment. AB - BACKGROUND AND OBJECTIVE: It is important to determine which patients with mild cognitive impairment (MCI) are at risk for progression to dementia. The presence of mild impairments not restricted to the domain of memory may suggest such progression. Our goal is to determine how well a visuospatial problem solving task assessing the cumulative burden of frontal and posterior damage differentiates MCI patients from matched controls. METHODS: Twenty-six patients with MCI [Clinical Dementia Rating (CDR) score of 0.5] and mini-mental state examination (MMSE) scores of at least 24/30, were compared with 20 age and education level matched controls without cognitive impairment. All patients were given the MMSE, Hopkins Verbal Learning Test (HVLT), Boston Naming Test (BNT), Rey Complex Figures copying (RCF), anagrams, and visuospatial problem solving battery (VPS). The VPS is a complex problem solving task, which we predicted would better discriminate patient groups than the relatively simpler tasks. RESULTS: Differences existed between groups on most tasks, but logistic regression revealed that the VPS discriminated the 2 groups better than the other nonmemory cognitive tests. CONCLUSIONS: The VPS, a problem solving task assessing the cumulative burden of frontal and posterior damage is more sensitive for detecting nonmemory impairments in MCI than other tasks. Future research will be needed to determine if impairment in the VPS is a sensitive predictor of progression to dementia or treatment response. PMID- 17356345 TI - A case-controlled study of altered visual art production in Alzheimer's and FTLD. AB - OBJECTIVE: To characterize dementia-induced changes in visual art production. BACKGROUND: Although case studies show altered visual artistic production in some patients with neurodegenerative disease, no case-controlled studies have quantified this phenomenon across groups of patients. METHOD: Forty-nine subjects [18 Alzheimer disease, 9 frontotemporal dementia (FTD), 9 semantic dementia (SD), 15 healthy older controls (NC)] underwent formal neuropsychologic testing of visuospatial, perceptual, and creative functioning, and produced 4 drawings. Subjective elements of drawings were rated by an expert panel that was blind to diagnosis. RESULTS: Despite equal performance on standard visuospatial tests, dementia groups produced distinct patterns of artistic features that were significantly different from NCs. FTDs used more disordered composition and less active mark-making (P<0.05). Both FTDs and SDs drawings were rated as more bizarre and demonstrated more facial distortion than NCs (P<0.05). Also, SDs drastically failed a standardized test of divergent creativity. Alzheimer disease artwork was more similar to controls than to FTDs or SDs, but showed a more muted color palette (P<0.05) and trends toward including fewer details, less ordered compositions, and occasional facial distortion. CONCLUSIONS: These group differences in artistic style likely resulted from disease-specific focal neurodegeneration, and elucidate the contributions of particular brain regions to the production of visual art. PMID- 17356346 TI - The Semantic Object Retrieval Test (SORT) in amnestic mild cognitive impairment. AB - BACKGROUND: Between 10% and 15% of patients with the amnestic variety of Mild Cognitive Impairment (MCI) convert to Alzheimer disease (AD) per year. OBJECTIVE: Characterize cognitive markers that may herald conversion from MCI to AD and directly assess semantic memory in patients meeting criteria for amnestic MCI. DESIGN: Thirty-five amnestic MCI patients and 121 healthy aging controls enrolled at an Alzheimer Disease Center received a battery of standard neuropsychologic tests, and the Semantic Object Retrieval Test (SORT), a test that we have developed for the assessment of semantic memory and subsequent name production, and that has been shown to be able to differentiate between normals and patients with AD. RESULTS: On the basis of normative data from the SORT, the MCI subjects could be divided into 2 groups: 10 patients (29%) with a significant semantic impairment (SI+) and 25 without a semantic memory deficit (SI-). There was a significant correlation between all SORT variables and performance on the Boston Naming Test. In this MCI population, significantly impaired SORT performance was associated with a relative decrease in performance on tests of frontal lobe functions, although disruption of thalamic-related processes cannot be excluded as an etiology for semantic memory impairment. CONCLUSIONS: The SORT is a specific test of semantic memory, and is a sensitive measure of semantic memory deficits in patients who otherwise meet criteria for amnestic MCI. Using this specific assessment tool, a significant number of MCI patients were found to have semantic memory deficits. As these patients may be early in the course of possible progression toward dementia, the SORT or other tests of semantic memory may provide important diagnostic or prognostic information in patients with MCI. PMID- 17356347 TI - Educational level as a modulator of cognitive performance and neuropsychyatric features in Parkinson disease. AB - OBJECTIVES: To test a possible association between the educational level (EL), cognitive performance, and neuropsychiatric features in Parkinson disease (PD). BACKGROUND: An inverse association has been reported between EL and cognitive dysfunction in patients with senile dementia of Alzheimer type but it is yet unsettled whether education has a similar effect on cognition in PD. METHODS: Seventy-two PD patients (45 males, mean age 68.7+/-11.6 y) underwent a detailed neurologic examination, a battery of neuropsychologic tests, and questionnaires for the evaluation of psychosis, sleep disturbances, and depression. According to the number of educational years, patients were divided into 3 groups: low EL (0 to 8 y), (15 patients), intermediate EL (9 to 12 y) (28 patients), and high EL (>/=13 y) (29 patients). RESULTS: Patients with a higher EL had a better cognitive function and an association was found between the patients' EL and their scores in various neuropsychologic tests mainly those sensitive to frontal lobe dysfunction. Low education was associated with an increased risk for hallucinations and a trend for more depression, delusions, and sleep disturbances. CONCLUSIONS: The association between high educational attainment and the lower risk of cognitive dysfunction suggest that education might modulate cognitive performance in PD. PMID- 17356348 TI - Blood pressure variability and dementia rating scale performance in older adults with cardiovascular disease. AB - OBJECTIVE: The present study examined the relationship between multiple indices of blood pressure (BP) and cognitive function (as measured by the Dementia Rating Scale). BACKGROUND: Cardiovascular disease (CVD) is associated with cognitive dysfunction and cerebrovascular pathology in the elderly and is a known risk factor for stroke and Alzheimer disease. Yet, the mechanisms for the effects of CVD on cognitive function are not well understood. METHODS: Participants were 97 nondemented older adults with CVD who underwent neuropsychologic assessment, and a 2-hour cardiovascular laboratory protocol. RESULTS: After controlling for age and years of education, results of hierarchical linear regression analyses indicate a significant positive relationship between a function of BP variability (SD of systolic BP divided by the average diastolic BP) and cognitive function (R change=0.042, F (1, 85)=5.434, P<0.05). No relationship emerged between any other BP index and cognitive function. CONCLUSIONS: Contrary to expectations, greater BP variability was associated with better, not poorer, cognitive test performance. These findings suggest that the relationship between BP and cognitive function is more complicated than originally conceptualized and requires further investigation. PMID- 17356350 TI - Management of hypertensive emergencies: implications for the critical care nurse. AB - Hypertensive emergencies are characterized by acute blood pressure elevations and potential for end organ damage. The critical care nurse must understand the pathophysiology to appreciate the therapeutic management and complications associated with the devastating clinical event. Stroke, renal damage and failure, retinopathy, aortic dissection, and encephalopathy are among the sequelae of severe hypertensive episodes. Intravenous medications are the treatment of choice to lower the blood pressure without risking hypoperfusion of the brain and other vital organs. PMID- 17356351 TI - Management of acute decompensated heart failure. AB - Heart failure, a debilitating complex clinical syndrome, affects nearly 5 million people in the United States and presents a heavy socioeconomic burden. Neurohormonal abnormalities contribute to the pathophysiology of heart failure. Acute decompensated heart failure (ADHF) has emerged as a major health problem associated with poor prognosis, increased costs related to care, reduced quality of life, and frequent readmissions. Symptoms of ADHF are primarily related to congestion and/or low perfusion states. The use of biomakers such as B natriuretic peptides is useful in distinguishing between cardiac and noncardiac causes of symptoms. Treatment for ADHF begins with identification and treatment of precipitating factors for acute decompensation. Initial goal of therapy is focused on symptom management followed by interventions that delay disease progression, reduce readmission, and prolong survival. PMID- 17356352 TI - Ventricular assist devices in the adult. AB - Ventricular assist devices (VADs) play an increasingly important role in the care of cardiovascular patients. Developed initially for support of cardiothoracic surgery patients experiencing difficulty in weaning from cardiopulmonary bypass, these devices have been used extensively as a bridge to cardiac transplantation for patients who are failing on medical management. Research has demonstrated the effectiveness of a VAD as destination therapy, providing a permanent means of support for patients with advanced heart failure who are not eligible for heart transplantation. Applications for VADs are expanding and advances in technology occurring to support these new applications. This article provides an overview of current and emerging VADs and nursing management of the VAD patient. PMID- 17356354 TI - Mechanical circulatory support for the pediatric patient. AB - In adult patients, mechanical circulatory support (MCS) devices are part of the standard of care for heart failure. There are several options available that clinicians may use to provide support for their patients and thus the choice of devices can be tailored to their individual needs. Unfortunately, this is not the case for pediatric patients with heart failure, where the options for MCS modalities are far more limited because of size constraints and regulatory hurdles. Furthermore, the pathophysiology of heart failure in children is not identical to that of adults; thus, the device selection and configuration require different considerations. Management of pediatric patients on MCS requires a highly specialized team of pediatric professionals. The nurse caring for a child on MCS is an active participant in all aspects of the patient's care and must have an in-depth understanding of the patient's underlying physiology, the circulatory physiology of the MCS system, the reason for mechanical support, and the goal of support. PMID- 17356355 TI - Bringing research to the bedside: the role of induced hypothermia in cardiac arrest. AB - Despite progress in resuscitative practices, there has been little improvement in mortality and neurologic morbidity outcomes after cardiac arrest. Updated resuscitative guidelines were published in 2005, and included changes in resuscitation measures and recommendations in postresuscitation interventions including induced hypothermia. Treatment with induced hypothermia after cardiac arrest for up to 24 hours has been shown to significantly improve the neurologic outcomes and mortality in patients with primary cardiac arrest who remain comatose after return of spontaneous circulation. St. Luke's Episcopal Hospital, a private, not-for-profit teaching hospital licensed for 949 beds located at the Texas Medical Center in Houston, Tex, has incorporated this research into practice. A multidisciplinary team led by a neurointensivist was formed to develop and implement a protocol to support induced hypothermia after cardiac arrest. Twenty-five patients have received induced hypothermia with a 74% survival rate. Of those who survived, 47% went home for a regular discharge, 29% transferred to acute rehabilitation, and 23% transferred to a long-term care facility. PMID- 17356356 TI - Statin therapy: not just used to lower cholesterol? AB - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, also known as statins, are the cornerstones of treatment of hyperlipidemia. They are widely used drugs that have well-documented, advantageous effects on cholesterol and atherosclerosis. The pleiotropic activities of statins can lead to newer applications. This review describes some of the available evidence supporting the use of statins for the treatment of acute coronary syndrome, as adjuncts to percutaneous coronary intervention, and for the prevention of sepsis. It also briefly discusses the rationale behind the potential development of statin eluting stents. PMID- 17356357 TI - C-reactive protein, stroke, and statins. AB - C-reactive protein (CRP) is an important indicator and player in inflammatory diseases such as stroke. It may be involved in the earliest stages of stroke. Monitoring the levels of CRP may help in the prevention and treatment of stroke. Statin drugs may be useful in lowering CRP levels and the incidence of stroke. PMID- 17356358 TI - Practical cardiac auscultation. AB - This article focuses on the practical use of the stethoscope. The art of the cardiac physical examination includes skillful auscultation. The article provides the author's personal approach to the patient for the purpose of best hearing, recognizing, and interpreting heart sounds and murmurs. It should be used as a brief introduction to the art of auscultation. This article also attempts to illustrate heart sounds and murmurs by using words and letters to phonate the sounds, and by presenting practical clinical examples where auscultation clearly influences cardiac diagnosis and treatment. The clinical sections attempt to go beyond what is available in standard textbooks by providing information and stethoscope techniques that are valuable and useful at the bedside. PMID- 17356359 TI - Perceived needs of critical care family members: a phenomenological discourse. AB - A phenomenological study with Heideggerian hermeneutic contextual analysis was used to illuminate the perceived needs of family members who were in the critical care waiting room. Family members freely expressed their perceptions of perceived needs, and thick descriptions supported 4 explicit needs expressed by all participants. These needs were seeking information, trusting the professionals, being a part of the care, and maintaining a positive outlook. The dialogues of the participants were presented to develop awareness and stimulate conversation regarding the needs of family members in the critical care waiting room who are an integral part of the healing process of patients in the critical care unit. PMID- 17356362 TI - Hardware, software, brainware. PMID- 17356360 TI - Implementing a bar-coded bedside medication administration system. AB - Hospitals across the nation are struggling with implementing electronic medication administration and reporting (eMAR) systems as part of patient safety programs. St Luke's Hospital in Chesterfield, Mo, initiated their eMAR initiative in June 2003, initiating program start-up in September 2004. This case study documents how the project was approached, its overall success, and what was learned along the way. Also included is a recent update highlighting the expansion of St Luke's patient safety initiative, adapting eMAR to two specialty units: dialysis and laboratory processes. PMID- 17356363 TI - Ralph V. McKinney Jr. Annual Award in Basic and Clinical Research for 2006. PMID- 17356364 TI - The Perel Educator's Award. PMID- 17356365 TI - The Charles E. English Annual Award in Clinical Science and Techniques for 2006. PMID- 17356366 TI - Four ways to increase implant case presentation. PMID- 17356367 TI - Multitier technique for bone augmentation using intraoral autogenous bone blocks. AB - PURPOSE: Intraoral bone grafts are a convenient and acceptable source of autogenous bone for alveolar reconstruction due to bone origin similarity and less morbidity. In large bone defects, 1 tier might be insufficient to achieve the desired bone shape. The purpose of this article was to describe a multitier technique for reconstruction of extensive bone deficiency, using only intraoral block bone grafts for implant site augmentation. MATERIALS: After clinical and radiographic evaluation of the recipient site, measurements were taken to determine the size of the bone deficiency. The first tier of bone graft was harvested from the mandibular ramus. After additional clinical and radiographic evaluation of the recipient site 5 months later, bone graft blocks for the second tier were harvested either from the second ramus or the mandibular symphysis. CONCLUSIONS: A new technique, the multitier intraoral bone block graft, for the future use of dental implants, is described. This technique can serve as an optional operation procedure for extensively atrophic alveolar bone augmentation. PMID- 17356368 TI - Medical contraindications to implant therapy: Part II: Relative contraindications. AB - Systemic conditions and habits influence dental implant survival to varying degrees. Illnesses that impair the normal healing cascade worsen surgical success. The mere presence of a disease, however, does not necessarily preclude implant therapy or affect significantly long-term outcomes. Certain disorders, when controlled, or other situations allow implant survival rates that match those in health. This paper reviews these relative contraindications, which include adolescence, aging, osteoporosis, smoking, diabetes, positive interleukin 1 genotype, human immunodeficiency virus positivity, cardiovascular disease, and hypothyroidism. PMID- 17356369 TI - Bifid mandibular canal in Japanese. AB - The location and configuration of mandibular canal variations are important in surgical procedures involving the mandible, such as extraction of an impacted third molar, dental implant treatment, and sagittal split ramus osteotomy. We report 3 Japanese patients with bifid mandibular canals using panoramic radiograph and multi-slice helical computed tomography (CT) images. In 2 of the 5 sides, the bifid mandibular canal was suggested on panoramic radiograph. The bifid mandibular canal had a short and narrow upper canal toward the distal area of the second molar in 4 sides, and a short and narrow lower canal toward the distal area of second molar in 1 side, as revealed on reconstructed CT images. Since the location and configuration of mandibular canal variations are important in surgical procedures involving the mandible, they should be carefully observed using reconstructed CT images. PMID- 17356370 TI - Mineralized bone allograft-plug socket augmentation: rationale and technique. AB - BACKGROUND: Socket augmentation allows clinicians to preserve alveolar bone height. This, in turn, could maintain adjacent soft tissue (papillae) height to promote optimal implant esthetics. MATERIALS AND METHODS: A new regimen for the socket augmentation technique (the mineralized bone allograft-plug technique) is introduced. It uses solvent-preserved mineralized cancellous allografts to fill the sockets up to 1-2 mm below the bone crest. This is covered with a bioabsorbable collagen wound dressing (CollaPlug; Zimmer Dental, Carlsbad, CA). Illustrations to demonstrate the technique are introduced. A case treated with this approach is presented. RESULTS: This technique is easy to perform with minimal trauma. Both clinical observation and histological results showed excellent bone formation. CONCLUSION: Our clinical experience, as well as histologic data, suggest that the mineralized bone allograft-plug is a suitable technique for socket augmentation. PMID- 17356371 TI - A histomorphogenic analysis of bone grafts augmented with adult stem cells. AB - PURPOSE: To evaluate the influence of bone marrow aspirate added to xenograft or alloplast graft matrix scaffold to produce bone. MATERIALS: A maximum of 4 cc bone marrow was aspirated from the anterior iliac crest of 5 patients to saturate the matrix scaffold prior to bone graft. Seven graft sites evaluated included sinus lift augmentation, particulate onlay graft of the maxilla via a tunneling procedure, and particulate onlay graft of the maxilla stabilized with titanium mesh. The xenograft scaffold was either PepGen Putty (DENTSPLY Friadent CeraMed, Lakewood, CO) or C-Graft resorbable algae material (Clinician's Preference, Golden, CO). The alloplast scaffold was beta-tricalcium phosphate (either Curasan AG, Kleinostheim, Germany, or Vitoss; Malvern, PA). RESULTS: Graft sites healed for 4-7 months. Core specimens of graft sites were taken with trephine drills, and submitted for standard histologic and histomorphogenic analysis. The percentage of graft material converted into bone, percentage of vital graft matrix, percentage of unresorbed matrix, and percentage of remaining interstitial tissue were measured. After a 4-month healing of sinus-lift augmentation with C Graft, the biopsy showed 31% bone that was 100% vital. Unresorbed graft material was 26%, and remaining interstitial material constituted 43%. Using pure phase beta-tricalcium phosphate, a 4-month core biopsy showed 40% bone that was 100% vital. Residual graft was 3% and interstitial material 57%. A sinus grafted with PepGen P-15 (DENTSPLY Friadent CeraMed) was found to be 14% bone, with 100% of that bone vital. The non-bone within the core was 36%. After a 4 1/2-month healing of bilateral sinus grafts using a nonpure phase beta-tricalcium phosphate, the percentage of the biopsy that was bone was 23% on the right side and 16% on the left side. Vital bone was 89% (right side) and 86% (left side). The core taken after 4 months of healing from the anterior maxilla particulate onlay graft with PepGen P-15 showed 32% bone, with 100% found to be vital. Non bone within the core was 15%, and 53% was interstitial material. After 7 months of healing, a biopsy core from the maxillary ridge augmented with C-Graft was 45% newly formed bone, with 100% of the bone vital. There was no residual graft material present. DISCUSSION: Bone regeneration by cell-based strategies depends upon an understanding of the biology and potential of adult stem cells as a method of regenerating bone. CONCLUSIONS: Bone marrow aspirate containing adult stem cells when mixed with bioengineered graft materials provide a scaffold to support the proliferation, differentiation, and maturation of the stem cells, as well as facilitating angiogenesis. This article presents histological evidence that stem cells aspirated from bone marrow and transplanted onto biocompatible scaffolds can successfully regenerate bone. This new standard for bone grafting may emerge as an alternative to autogenous bone grafts. PMID- 17356372 TI - Aesthetics in oral implantology: biological, clinical, surgical, and prosthetic aspects. AB - OBJECTIVES: The aim of this study was to identify a correct clinical, surgical, and prosthetic management of endosseous implants replacing missing teeth in the anterior maxilla, achieving predictable aesthetic outcomes. Placement of immediate post-extraction implants without incisions or flap elevation is one of the surgical treatment options able to improve the healing and regenerative potentials of the fresh socket. MATERIALS: Fifty-five patients (33 men, 22 women), ranging in age from 19 to 57 years (mean 29), were selected for this study. All the patients were not smokers, no bruxers, presented stable soft tissue conditions, an acceptable occlusion, and the absence of pathologies that would contraindicate bone healing. Patients were treated with implants made by 2 manufacturers: Institute Straumann, Walderburg, Switzerland and Friadent, Mannheim, Germany. A total of 87 implants were placed immediately after each failing tooth had been removed. The temporary restoration was placed 3 months after implant placement, and the final restoration was placed 4 months from the surgical procedure. The patients were evaluated clinically and radiographically at implant placement, and 2, 4, 18, and 24 months post-insertion. RESULTS: At 24 months, only 3 implants were lost (2 in male patients;1 in female patient). All of these failed implants did not achieve osseointegration. The overall success rate was 96.6%, with an implant failure rate of 3.4%, all prior to restoration. CONCLUSIONS: The immediate placement in the anterior maxilla fresh extraction sockets without incisions or flaps elevation is a surgical option that can ensure ideal peri-implant tissues healing, preserving the presurgical gingival and bone aspects. For a predictable aesthetic result, the most important aspect seems to be the height and thickness of the buccal bone wall, which remain after immediate placement of the fixture. PMID- 17356373 TI - The integration of chitosan-coated titanium in bone: an in vivo study in rabbits. AB - PROCEDURE: Much research is directed at surface modifications to enhance osseointegration of implants. A new potential coating is the biopolymer, chitosan, the deacetylated derivative of the natural polysaccharide, chitin. Chitosan is biocompatible, degradable, nontoxic, and exhibits osteogenic properties. The aim of this research was to investigate the hypothesis that chitosan-coated titanium supports bone formation and osseointegration. MATERIALS AND METHODS: Chitosan (1 wt% of 92.3% deacetylated chitosan in 1% acetic acid) was solution cast and bonded to rough ground titanium pins (2-mm diameterx4-mm long) via silane reactions. Calcium phosphate sputter-coated titanium and uncoated titanium pins were used as controls. Two chitosan-coated pins, and 1 each of calcium phosphate coated and uncoated pins were implanted unilaterally in the tibia of 16 adult male New Zealand white rabbits. At 2, 4, 8, and 12 weeks, undecalcified sections were histologically evaluated for healing and bone formation. RESULTS: Histological evaluations of tissues in contact with the chitosan-coated pins indicated minimal inflammatory response and a typical healing sequence of fibrous, woven bone formation, followed by development of lamellar bone. These observations were similar to those for tissues interfacing the control calcium phosphate-coated and uncoated titanium implants. Quantitative comparisons of the bone-implant interface were not possible since 31% of the implants migrated into the tibial marrow space after implantation due to insufficient cortical bone thickness to hold pins in place during healing. CONCLUSION: These data support the hypothesis that chitosan-coatings are able to develop a close bony apposition or the osseointegration of dental/craniofacial and orthopedic implants. PMID- 17356374 TI - Effect of tumor necrosis factor-alpha gene polymorphism on peri-implant bone loss following prosthetic reconstruction. AB - PURPOSE: The present study investigates the association between a specific polymorphism in the tumor necrosis factor (TNF)-alpha gene, consisting of allele 2 of TNF-alpha-308, and peri-implant bone loss following prosthetic reconstruction. MATERIALS AND METHODS: This case-control study included 36 patients (20 women, 16 men; mean age 46 years) who had used implant-supported prostheses for a minimum of 6 months and a maximum of 31 months. The patients were nonsmoking, white Caucasian Brazilians, in good general health, and were not receiving medication. In the case group, patients exhibited 1 or more implants with a diagnosis of peri-implant bone loss following prosthetic reconstruction; control patients had 1 or more healthy implants. RESULTS: Polymorphism in the TNF alpha gene, allele 2 of TNF-alpha, was not associated with an increased risk for peri-implant bone loss following prosthetic reconstruction (P=0.19; chi2=1.71; df=1), although 21.1% of the subjects carried allele in the control group 2, and 41.2% carried allele 2 in the case group. CONCLUSIONS: Polymorphism in allele 2 of the TNF-alpha-308 gene is not associated with an increased risk for peri implant bone loss following prosthetic reconstruction. However, further studies based on a greater number of patients are necessary. PMID- 17356375 TI - Antibacterial effect of zinc phosphate mineralized guided bone regeneration membranes. AB - PURPOSE: Current commercial guided bone regeneration membranes are susceptible to bacterial colonization, leading to premature membrane degradation. The purpose of this research is to modify current resorbable guided bone regeneration membranes with antibacterial property by mineralizing with zinc phosphate. MATERIALS: Resolut Adapt LT (Gore-Tex; W.L. Gore & Associates, Inc., Flagstaff, AZ), composed of copolymer PGA/TMC, and BioMend Extend (Zimmer Dental, Carlsbad, CA), composed of bovine type 1 collagen, were used. The membranes were mineralized with zinc phosphate. The mineralized membranes were characterized using scanning electron microscopy, energy dispersive spectroscopy, x-ray diffraction, Fourier transform infrared spectroscopy, inductive coupled plasma, and thermogravimetry. Antibacterial property of zinc phosphate mineralized and nonmineralized membranes were determined using Actinobacillus actinomycetemcomitans standard strain ATCC 29522. RESULTS: Scanning electron microscopy, energy dispersive system, and Fourier transform infrared identified zinc phosphate in the zinc phosphate mineralized membranes. Zinc phosphate mineralized membranes showed significant reduction in bacterial colony, forming units compared to nonmineralized membranes. CONCLUSION: Results of this study suggest that the use of zinc phosphate mineralized membranes can inhibit oral bacterial colonization and prevent inflammation due to membrane exposure. This antibacterial property may help achieve the optimal goal of guided bone regeneration. PMID- 17356376 TI - Genotoxicity of corrosion eluates obtained from endosseous implants. AB - PURPOSE: Commercially pure titanium alloys are currently used as metallic biomaterials in implantology. Corrosion phenomena appear to play a decisive role in metallic implant long-term behavior. Thus, the goal of this study was to examine the genotoxic potential of corrosion eluates obtained from dental implants using Chinese ovary hamster cells in vitro by the single-cell gel (comet) assay. This technique detects deoxyribonucleic acid strand breaks in individual cells in alkaline conditions. MATERIALS AND METHODS: The materials tested included 3 dental implants commercially available. Each of the tested materials was corroded in a solution consisting of equal amounts of acetic acid and sodium chloride (0.1 M) for 1, 3, 7, 14, and 21 days. The Chinese ovary hamster cultures were then exposed to all corrosion eluates obtained from endosseous dental implants for 30 minutes at 37 degrees C. RESULTS: None of the eluates was found to exhibit genotoxicity, regardless of the type of dental implant used. CONCLUSION: The results suggest that all dental implants tested in this study did not induce deoxyribonucleic acid breakage as depicted by the single-cell gel (comet) assay. PMID- 17356377 TI - Knowledge, attitude, and practice of dental implantology in Nigeria. AB - AIM: The purpose of this study was to assess the knowledge, attitude, and practice of dental implantology among dentists practicing in Nigeria. MATERIALS: Self-administered questionnaires to assess the knowledge, practice, and attitude of dental implantology were sent to dentists practicing in all the 6 geopolitical zones of Nigeria (i.e., all tertiary dental institutions, and selected general and private hospitals within the zones). Data collected were analyzed and presented in descriptive and tabular forms. RESULTS: The response rate was 77%. Only 2 (1.3%) of the respondents claimed to have employed implant(s) for dental restoration in their practice, while 152 respondents (98.7%) have never used implants as a method of tooth/teeth restoration. Of the latter, 46.1% have suggested implants for full/partial denture patients, 31.8% have suggested dental implants to patients needing single-tooth replacement, and 89.6% were ready for dental implant placement if equipment and materials for dental implants backed up with adequate training were provided. Of respondents, 83.1% also believed that implantology is a multidisciplinary approach, and 42.9% rated implants as the best option for dental restoration. CONCLUSIONS: The practice of implant dentistry is presently very low in Nigeria. Clearly, there is a need for dental implant education for Nigerian dentists to increase their knowledge and proficiency in dental implant dentistry. In addition, all efforts should be made to include implant education and practice in dental curricula in undergraduate and postgraduate institutions in Nigeria. PMID- 17356378 TI - Molecular mechanisms of astrogliosis: new approaches with mouse genetics. AB - Astrocytes are increasingly being recognized as dynamic participants in many aspects of normal central nervous system function. In disease states, reactive astrocytes undergo complex phenotypic changes, generically referred to as astrogliosis. Unraveling the functions of reactive astrocytes and underlying molecular mechanisms is a difficult problem. The use of genetically modified mice is beginning to yield some answers to long-standing questions in the field. What are the functions of reactive astrocytes? What extracellular factors and intracellular signaling mechanisms are responsible for astrocyte activation in various forms of neural injury? In this review we will highlight studies using astrocyte reporter lines for cellular imaging and lineage tracing, as well as gain- and loss-of-function mutations that have begun to shed light on mechanisms of astrogliosis. PMID- 17356379 TI - TDP-43-positive white matter pathology in frontotemporal lobar degeneration with ubiquitin-positive inclusions. AB - TDP-43 was recently identified as the major disease protein in neuronal inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). TDP-43 is not only linked to disease mechanisms in FTLD-U, but it is also the most robust marker for the specific detection of neuronal inclusions in FTLD-U. In this study, we describe additional TDP-43 pathology in the white matter as a characteristic feature in a series of 38 FTLD-U cases including 3 cases with mutations in the progranulin gene. White matter pathology was most abundant in frontal and temporal lobes, but it was also detectable in brainstem and spinal cord. Based on morphology and double-labeling experiments, white matter cells with TDP-43-positive inclusions most likely represent oligodendrocytes. Biochemically, hyperphosphorylated and truncated TDP-43 was detectable in insoluble brain extracts from affected white matter regions in FTLD U, similar to the biochemical signature observed in FTLD-U gray matter. Taken together, these results expand the spectrum of TDP-43 pathology in FTLD-U, suggesting that white matter pathology might contribute to the neurodegenerative process and clinical symptoms in FTLD-U. PMID- 17356380 TI - Characterization of the early neuroinflammation after spinal cord injury in mice. AB - The occurrence of neuroinflammation after spinal cord injury (SCI) is well established, but its function is debated, with both beneficial and detrimental consequences ascribed. A discriminate of the role of neuroinflammation may be the time period after SCI, and there is evidence to favor early neuroinflammation being undesirable, whereas the later evolving phase may have useful roles. Here, we have focused on the inflammatory response in the first 24 hours of SCI in mice. We found elevation of interleukin (IL)-1beta and other cytokines and chemokines within 15 minutes to 3 hours of injury. The early neuroinflammation in SCI is likely to be CNS-derived and involves microglia, as demonstrated by in situ hybridization for IL-1beta in microglia, by an in vitro model of SCI in which elevation of inflammatory cytokines occurs in the absence of a dynamic source of infiltrating leukocytes, and by the correlation of decreased levels of inflammatory molecules and microglia activity in IL-1beta-null mice. Nonetheless, as there are no specific immunohistochemical markers that clearly differentiate microglia from their peripheral counterparts, macrophages, the latter cannot be definitively excluded as participants in early neuroinflammation in mouse SCI. These results of an instantaneous inflammatory response validate approaches to modulate microglia/macrophage activity to improve recovery from SCI. PMID- 17356381 TI - Changes in the expression pattern of the nitrergic system of ovine cerebellum affected by scrapie. AB - The constitutive and inducible isoforms of nitric oxide synthase (NOS) and the end-product of nitration, nitrotyrosine, were analyzed by immunohistochemistry, Western blotting, and enzymatic activity in sheep at different stages of the prion disease, scrapie. Four groups were studied: 1) nonaffected (control), 2) preclinical, 3) clinical, and 4) terminal. Constitutive neuronal NOS (nNOS) was the most abundant isoform present in cerebellar neurons of the sheep. Expression of nNOS increased in preclinical animals but diminished in the late stages of the disease. The Purkinje cells that usually are not immunoreactive for this protein became immunopositive in the clinical phase. In unaffected sheep, the inducible isoform (iNOS) was slightly positive in the Purkinje cells. As the disease progressed, the immunoreactivity of Purkinje neurons for iNOS increased. At the final stages, numerous iNOS-positive microglial cells were found in the molecular layer. There was a basal level of protein nitration in the cerebellum of unaffected sheep, especially in the molecular layer. As the disease progressed, the distal prolongations of the Purkinje cells and the astroglia became immunoreactive for nitrotyrosine. Our results suggest that the nitrergic system reacts to the progression of spongiform diseases and may be part of their pathogenesis mechanism. PMID- 17356382 TI - High production of CXCL13 in blood and brain during persistent infection with the relapsing fever spirochete Borrelia turicatae. AB - Relapsing fever (RF) is a multisystemic borrelial infection with frequent neurologic involvement referred to as neuroborreliosis. The absence of an effective antibody response results in persistent infection. To study the consequences to the brain of persistent infection with the RF spirochete Borrelia turicatae, we studied B cell (Igh6-/-) and B and T (Rag1-/-) cell-deficient mice inoculated with isogenic serotypes 1 (Bt1) or 2 (Bt2). We found that Bt1 was more tissue tropic than Bt2, not only for brain but also for heart. Igh6-/- mice developed more severe clinical disease than Rag1-/- mice. Bt1-infected brains had widespread microgliosis/brain macrophage activation despite localization of spirochetes in the leptomeninges rather than the brain parenchyma itself. Oligoarray analysis revealed that CXCL13 was the most upregulated gene in the brain of Bt1-infected Igh6-/- mice. CXCL13 was also the most abundant of the chemokines we measured in infected blood. Persistent infection did not result in injury to the brain. Treatment with exogenous interleukin-10 reduced microgliosis in the brain and production of CXCL13 in the blood. We concluded that brain involvement in B cell-deficient mice persistently infected with B. turicatae is characterized by prominent microgliosis and production of CXCL13 without detectable injury. PMID- 17356383 TI - Perisomatic thalamic axotomy after diffuse traumatic brain injury is associated with atrophy rather than cell death. AB - Morbidity and mortality associated with traumatic brain injury (TBI) stem from diffuse axonal injury (DAI) throughout subcortical and brainstem white matter and subcortical nuclei. After midline fluid percussion brain injury, DAI in the thalamus includes perisomatic axotomy and resembles human post-traumatic pathology where the degree of morbidity correlates with thalamic damage. After axotomy, acute somatic perturbations resolve and appear compatible with cell survival; however, the long-term fate of neurons in an area with perisomatic axotomy is unknown. From brain-injured and uninjured rats at 1, 7 and 28 days after injury (injury, n = 5/group; sham, n = 4), alternate sections were immunostained for amyloid precursor protein (APP) to detect perisomatic axotomy or Giemsa stained for quantification of neuronal number, neuronal density, regional volume, and neuronal nuclear volume using design-based stereology. One day postinjury, APP-immunoreactive axons were identified consistently within the perisomatic domains of thalamic neurons of the ventral basal complex. Bilateral systematic-random quantification of the ventral basal complex indicated a significant reduction in neuronal density (number per mm, but not number alone) at 1 week after injury, compared with sham and 1 day postinjury. Furthermore, by 1 day and persisting through 1 week after injury, the mean neuronal nuclear volume was atrophied significantly compared with sham. Therefore, diffuse TBI results in early perisomatic axonal injury followed by neuronal atrophy in the ventral basal complex, without gross degeneration. Enduring atrophy in thalamic relays could underlie circuit disruption responsible for post-traumatic morbidity. PMID- 17356384 TI - Transcriptional profiling of the nuclear factor-kappaB pathway identifies a subgroup of primary lymphoma of the central nervous system with low BCL10 expression. AB - Recent studies point to a role of nuclear factor (NF)-kappaB signaling in a subset of diffuse large B cell lymphomas. We have analyzed the expression of 21 genes encoding NF-kappaB family members, upstream modulators, and targets in 32 primary central nervous system lymphomas (PCNSLs) by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with nonmalignant germinal center centroblasts, expression of BCL10, REL, IAP1, and TRAF1 was significantly lower in PCNSLs, whereas that of BAX, BCLXL, BCL2, MALT1, CARD9, CARD10, CARD11, CARD14, CCND2, cFLIP, RELA, RELB, NFKB1, NFKB2, and IRF4 was higher. Hierarchical clustering of gene expression data revealed two distinct subgroups of PCNSLs, which were characterized by significantly different transcriptional levels, predominantly of BCL10, but also of REL and IAP1. Thus, these quantitative RT-PCR data with expression of genes of the NF-kappaB family as well as NF-kappaB-regulated genes together with immunohistochemical detection of nuclear RELA and REL indicate activation of the NF-kappaB pathway in PCNSLs, which may contribute to their high proliferative activity and the low level of apoptosis. PMID- 17356385 TI - Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions. AB - The unambiguous identification of oligodendrocytes in tissue sections, especially in myelinated tracts, is often difficult. Most of the antibodies used to identify oligodendrocytes label the myelin sheath as well. Originally described as an inhibitor of axonal outgrowth, Nogo-A is known to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue. PMID- 17356386 TI - Re: "A possible cellular mechanism of neuronal loss in the dorsal root ganglia of dystonia musculorum (dt) mice". PMID- 17356388 TI - The diagnostic value of C-reactive protein, interleukin-8, and monocyte chemotactic protein in risk stratification of febrile neutropenic children with hematologic malignancies. AB - BACKGROUND AND AIM: Recent advances in febrile neutropenia have highlighted the value of risk stratification especially that it can have important implications in terms of management. We aimed to identify a serum marker that may help to stratify febrile neutropenic pediatric patients treated for hematologic malignancies at the time of first evaluation. Thus, C-reactive protein (CRP), interleukin-8 (IL-8), and monocyte chemotactic protein-1-alpha (MCP-1-alpha) were evaluated for their predictive and diagnostic relevance in febrile episodes of cancer patients. PATIENTS AND METHODS: Within 24 hours of fever, CRP, IL-8, and MCP-1 serum levels were measured and the levels of these markers were related to the clinical findings of the patients. For this purpose, we collected and analyzed clinical data of 85 fever episodes occurring in 76 patients with hematologic malignancies, presenting to the Department of Pediatric Oncology, National Cancer Institute, Cairo University, during a 6-month period. RESULTS: Neutropenic children with febrile episodes were classified into 2 groups, a group with unexplainable fever (group I, n=26) and another group with either blood culture positive, and/or fever periods with a documented clinical sepsis and/or local infection (group II, n=59). Clinically, local sites of infection were encountered in 39 cases (45.9%), whereas a positive blood culture was detected in 20 cases. CRP, IL-8, and MCP-1 levels were significantly lower in group I versus group II (P value <0.001). There were overlaps of values between groups. CRP > or =90 mg/L was significantly associated with chemotherapy-related neutropenia and fever owing to bacteremia (P=0.038). The sensitivity, specificity, negative and positive predictive values of CRP, MCP-1, and IL-8 were (70%, 73%, 51%, and 85%), (64%, 92%, 53%, and 95%), and (71%, 77%, 54%, and 88%), respectively. Combining 2 or 3 markers improved the diagnostic performance of these test, as 78% of group II had elevated 2 or 3 markers versus 16% of the group with no evident infection. CONCLUSIONS: Low levels of CRP, MCP-1, and IL-8 could identify patients with unexplainable fever; whereas, high levels of these markers were of help in the diagnosis of infectious episodes. A model combining more than 1 marker is recommended in the assessment of febrile neutropenia. PMID- 17356389 TI - Second trimester antenatal diagnosis in rare coagulation factor deficiencies. AB - Prenatal diagnosis is sought after for those genetic disorders, whose management is not satisfactory either because of the outcome or owing to extreme cost involved in the management of the patients affected by a specific disorder. Severe hemophilia and homozygous thalassemia are the 2 disorders for which there is an increasing demand for prenatal diagnosis in India. Rare severe deficiencies of coagulation factor X (FX) and factor VII (FVII) may present with severe bleeding manifestations. Because of their rarity the laboratory offering prenatal diagnosis for severe hemophilia and thalassemia may not be in a position to provide genetic diagnosis in the fetus. In this communication, we describe 2 families, 1 with an index patient of severe FVII deficiency and the other with severe FX deficiency where successful prenatal diagnosis was given after cordocentesis between 17 and 19 weeks using a battery of coagulation factor assays. Follow-up studies were performed 3 to 4 months after delivery and the diagnoses were reconfirmed on these babies by a repeat factor assay for FX and FVII deficiency, respectively. PMID- 17356390 TI - Prevalence, prevention, and treatment of microalbuminuria and proteinuria in children with sickle cell disease. AB - Microalbuminuria (MA) and proteinuria (P) are believed to be precursors of sickle cell nephropathy. We analyzed our longitudinal data on MA/P in children with sickle cell disease (SS) to define the age of onset, association with age, sex, and hemoglobin, and to explore the safety and efficacy of hydroxyurea and angiotensin converting enzyme inhibitor (ACEI) therapy. Data on 191 patients with SS (ages 3 to 20 y) with a mean follow up of 2.19 years+/-2.05 were available. Urine MA was measured yearly with follow-up testing if abnormal. Prevalence of MA/P was 19.4%. Increasing age and lower hemoglobin levels were related to MA/P but sex was not. Microalbumin excretion normalized in 44% of patients treated with hydroxyurea and 56% of patients treated with ACEI. Hyperkalemia developed in 4 ACEI patients resulting in discontinuation of treatment in 3 children. In summary, MA/P often develops in childhood and preventive and treatment strategies for sickle cell nephropathy should be a focus of pediatric programs. Our preliminary data suggest that although both hydroxyurea and ACEI therapy may be beneficial for MA/P, hyperkalemia may limit the utility of ACEI. PMID- 17356391 TI - Is the use of rFVIIa safe and effective in bleeding neonates? A retrospective series of 8 cases. AB - BACKGROUND: Recombinant activated factor VII (rFVIIa), originally developed for the treatment of life-threatening bleeding in hemophilic patients with inhibitors to factors VIII or IX, has been increasingly used to control hemorrhage unresponsive to conventional treatment, in the absence of a defined coagulopathy or thrombocytopathy. To date, clinical experience of rFVIIa administration in neonates, especially preterms, is rather limited, because of the lack of controlled studies and based solely on some published case reports and 1 prospective pilot study. The objective of this study was to retrospectively evaluate the clinical outcome of newborns treated with recombinant activated factor VII for intractable bleeding or severe coagulation disturbances, resistant to conventional hemostatic therapy. METHODS: The medical records of 8 neonates treated with rFVIIa (100 micro g/kg) were retrospectively reviewed for the course of hemorrhage and the hemostatic interventions performed before and up to 24 hours after the administration rFVIIa. Coagulation parameters of 3 different time points were assessed and compared: before administration of any blood product (time-point 1), before administration of the first dose of rFVIIa (time-point 2), and 4 hours after the administration of the last dose of rFVIIa (time-point 3). The safety and tolerability profile of rFVIIa in bleeding neonates was also evaluated. RESULTS: Six preterm and 2 term patients were included in the study. Seven patients presented with refractory bleeding and 1 was diagnosed with severe coagulopathy unresponsive to the conventional treatment. Prompt hemostasis was achieved in half of the patients with their coagulation profile being restored within 4 hours after the administration of the first dose of rFVIIa. Improvement in prothrombin time, activated partial thromboplastin time, and fibrinogen after rFVIIa administration was statistically significant, as compared with that observed after conventional treatment. No major safety issues were observed during the study. All 8 patients survived and had their hemorrhage or coagulopathy controlled within 4 hours after transfusion of the last dose of rFVIIa. CONCLUSIONS: In this study, the hemostatic agent rFVIIa was well tolerated and behaved in a safe and efficacious manner in all infants treated for life-threatening bleeding and coagulation disorders. Future prospective controlled trials are needed to determine the efficacy, safety, tolerability, and possibly the optimal dose and timing of rFVIIa administration. PMID- 17356392 TI - Study of pulmonary function tests in thalassemic children. AB - The present study aimed to investigate pulmonary function tests (PFTs) in children with thalassemia and to assess the relation between the degree respiratory impairment with the body iron status. High resolution computed tomography of chest (CHRCT) and bronchoalveolar lavage (BAL) was performed to study the cause of pulmonary dysfunction. Thirty-one children with thalassemia over 8 years were included. PFTs were studied including lung volumes and carbon monoxide diffusion capacity (DLco). Patients with abnormal PFTs and/or impaired DLco were further subjected to CHRCT and BAL. Total cell count was measured; differential count was performed on Giemsa and PAP smears. Iron laden macrophages were identified on Perl's stain. PFTs were normal in 51.61%, diffusion capacity impaired in 41.16%, restriction in 16.12%, while obstruction in 3.22% of cases, respectively. There was significant inverse correlation between DLco and serum ferritin. Through multivariate regression analysis, ferritin was found to be a strong predictor for forced vital capacity and total lung capacity. Bronchial dilatation and areas of air trapping were the predominant CHRCT findings. Iron laden macrophages were demonstrated in 14 of 15 patients in BAL. A significant correlation between serum ferritin and DLco, forced vital capacity, total lung capacity, and the presence of iron laden macrophages in BAL indicates that iron plays a major role in the etiopathogenesis of these abnormalities. PMID- 17356394 TI - Iron studies in infants born to an iron overloaded mother with beta-thalassemia major: possible effects of maternal desferrioxamine therapy. AB - A 30-year-old woman with transfusion-dependent, homozygous beta-thalassemia major and transfusional hemosiderosis had 2 successful pregnancies after ovulation induction and in vitro fertilization. Treatment with subcutaneous desferrioxamine (DF) was discontinued before the conception but restarted at 6 months of gestation. Elective cesarean section was performed at 35 weeks of pregnancy because of partial placenta previa. The infant was clinically normal. At the time of delivery, the maternal serum ferritin was 2000 ng/mL, serum iron/iron binding capacity (SI/TIBC) were 274/380 microg/dL, and % saturation 72%. Serum ferritin level in the infant was 42 ng/mL, SI/TIBC were 53/222 microg/dL, and % saturation 23%. During a twin pregnancy 2 years later, DF therapy was totally withheld. Elective cesarian section was performed at 36 weeks of gestation. Both twins were clinically normal. At delivery, the maternal serum ferritin was 1700 ng/mL, SI/TIBC 447/450 microg/dL, and % saturation 99%. Serum ferritins of the twins were 227 and 203 ng/mL, SI/TIBC were 30/182 and 27/203 microg/dL, and % saturations 16% and 13%. Despite elevated iron studies in the mother during both pregnancies, the SI/TIBC of the infants were quite low. In the first pregnancy in which DF was administered in last months of gestation, a low level of serum ferritin was present in the newborn that was even lower at 3 months of age. In the second pregnancy, high normal, levels of ferritin were present in both twin newborns. Despite comparable gestational ages, hemoglobin levels were lower in the first pregnancy than the second. These studies indicate that very high maternal levels of SI/TIBS and serum ferritin were not associated with increased fetal SI/TIBC, which were, in fact, quite low. Because of the different fetal ferritin levels in the 2 pregnancies, it is possible that treatment of the mother with DF in the last weeks of pregnancy may have resulted in depletion of fetal iron stores. PMID- 17356393 TI - Cerebral venous sinus thrombosis associated with essential thrombocytosis in a pediatric patient. AB - Essential thrombocytosis (ET) is an uncommon pediatric hematologic disorder that can result in thrombotic complications, including cerebral venous sinus thrombosis (CVST). Although CVST associated with ET is exceedingly rare, it can be devastating to the patient. We here report a pediatric case of CVST associated with ET. The patient was treated with hydroxyurea and warfarin, which was later replaced by low-dose aspirin. Platelet counts were well controlled after 16 months of follow-up, and no further thrombotic events occurred. Mucositis was the main adverse effect of treatment. PMID- 17356395 TI - Monitoring the isochromosome i(7)(q10) in the bone marrow of patients with Shwachman syndrome by real-time quantitative PCR. AB - Clonal chromosome anomalies may be found in the bone marrow (BM) of patients with Shwachman syndrome, who are at risk to develop myelodysplastic syndromes and/or acute myeloid leukemias. In particular, an isochromosome i(7)(q10) is frequent, and is usually monitored by chromosome analyses. We tested an approach by real time quantitative polymerase chain reaction (RQ-PCR) on a chromosome 7 polymorphism. Five DNA samples of 2 Shwachman syndrome patients with clonal i(7)(q10) in the BM were used. Both were heterozygous for the diallelic indel polymorphism MID1064, which maps in 7q35. The percentage of i(7)(q10)-positive cells was extrapolated from the ratio of the 2 alleles measured by means of an allele-specific RQ-PCR assay. The results were compared with cytogenetic analyses on the same material used for RQ-PCR. In 1 patient, the RQ-PCR results matched well with those of chromosome analyses, whereas in the other one RQ-PCR showed that around 40% of the BM cells were abnormal, while they resulted to be nearly 80% with conventional monitoring assays. As the results obtained by RQ-PCR refer to the DNA of around 128,000 BM cells, our method proved to be feasible and more efficient in the quantitative evaluation of the i(7)(q10)-positive clone than conventional ones. PMID- 17356396 TI - Epstein-Barr-associated leiomyomatosis and T-cell chimerism after haploidentical bone marrow transplantation for severe combined immunodeficiency disease. AB - BACKGROUND: The clinical course of Epstein-Barr virus (EBV)-associated smooth muscle tumors is variable and there are no reports in patients with mixed T-cell chimerism after bone marrow transplantation (BMT). OBSERVATIONS: A child with X linked severe combined immunodeficiency disease developed multiple renal and pulmonary leiomyomata 8 years after haploidentical BMT. Epstein-Barr viral DNA was detectable in the blood and in situ hybridization for EBV-encoded RNAs was positive in the tumor. The tumors have been radiographically stable, chimerism remains mixed, and plasma EBV DNA has been repeatedly negative for over 2 years after donor lymphocyte infusion. CONCLUSIONS: EBV-associated smooth muscle tumors may occur in patients who are partially reconstituted after BMT for severe combined immunodeficiency and may not require surgery or chemotherapy. PMID- 17356397 TI - Pulmonary hypertension in a case of Hb-Mainz hemolytic anemia. AB - The development of pulmonary arterial hypertension (PAH) is the leading cause of mortality in patients with thalassemia and sickle cell anemia and was reported to occur in hemolytic anemias such as hereditary stomatocytosis, and paroxysmal nocturnal hemoglobinuria. Here, we report for the first time on the development of PAH in a patient with Hb-Mainz hemolytic anemia. Hb-Mainz is an unstable hemoglobin variant resulting from mutations at codon 98 of the beta chain gene (Val>Glu) characterized by severe chronic hemolytic anemia. The development of PAH in this patient further supports the contention that there is a clinical syndrome of hemolysis-associated development of PAH. PMID- 17356398 TI - Successful treatment with liposteroid followed by reduced intensity stem cell transplantation in an infant with perforin deficiency presenting with hemophagocytic lymphohistiocytosis. AB - Perforin deficiency characterized by markedly reduced cytotoxic T and natural killer cell activities is one type of familial hemophagocytic lymphohistiocytosis (FHL). FHL is a fatal inherited disease, and treatment with stem cell transplantation has resulted in a normal activity of killer cells. We herein report a case of FHL with perforin deficiency that was primarily treated by the administration of liposteroid to reduce hypercytokinemia. Thereafter, allogenic bone marrow transplantation with nonmyeloablative conditioning was successfully performed without any adverse effects on the patient's physical or developmental status. These observations suggest that this treatment strategy might thus be recommended in infants with FHL to reduce treatment-related complications, especially in patients with relatively mild clinical courses. PMID- 17356400 TI - Paratesticular neuroblastoma: a case against metastatic disease? AB - Paratesticular lesions of neuroblastoma are in contrast to testicular infiltration extremely rare. Six cases were reported in literature. It is debated, whether localizations are either metastatic lesions or part of multicentric disease. We present a 9-month-old boy with stage 4 neuroblastoma, in which an unsuspected scrotal localization was already present at birth. This lesion had not grown, in contrast to the other sites. The case illustrates that neuroblastoma is a multicentric tumor, originating in the adrenal area and paratesticular sympathic remnants. The lesions differed in clinical behavior. It further illustrates that multicentric localizations exhibit different clinical behavior. PMID- 17356399 TI - Acute encephalopathy and cerebral vasospasm after multiagent chemotherapy including PEG-asparaginase and intrathecal cytarabine for the treatment of acute lymphoblastic leukemia. AB - A 7-year-old girl with an unusual reaction to induction chemotherapy for precursor B-cell acute lymphoblastic leukemia (ALL) is described. The patient developed acute encephalopathy evidenced by behavioral changes, aphasia, incontinence, visual hallucinations, and right-sided weakness with diffuse cerebral vasospasm on magnetic resonance angiography after the administration of intrathecal cytarabine. Vincristine, dexamethasone, and polyethylene glycol asparaginase were also administered before the episode as part of induction therapy. Neurologic status returned to baseline within 10 days of the acute event, and magnetic resonance angiography findings returned to normal 4 months later. PMID- 17356401 TI - Extracranial metastases of glioblastoma in a child: case report and review of the literature. AB - Glioblastoma (GBM) is the most common adult malignant brain tumor but is notably less common in children. Primary brain tumors rarely metastasize outside the central nervous system and when metastases occur, it is often in patients with diversionary shunting of the cerebrospinal fluid. This report details the case of a 13(1/2)-year-old boy who was diagnosed with GBM. He survived 10 months after diagnosis. At autopsy, the tumor was found to extensively infiltrate the leptomeninges as well as the cranial skin and soft tissue. Further examination disclosed multiple liver and lung metastatic GBM nodules. This pattern of spread is very uncharacteristic of gliomas and emphasizes the importance of adequate metastatic evaluation. PMID- 17356402 TI - Renal splenic heterotopia with extramedullary hematopoiesis in a thalassemic patient, simulating renal neoplasm: a case report. AB - Intrarenal splenic tissue (splenorenal heterotopia) is a rare condition. Simultaneous existence of splenorenal heterotopia and extramedullary hematopoiesis in a same patient can present as a mass of kidney. We present an interesting case of splenorenal heterotopia with extramedullary hematopoiesis in a thalassemic child simulating as a renal neoplasm. This is the first reported case in the right kidney. PMID- 17356403 TI - Primary tuberculosis of bone mimicking a lytic bone tumor. AB - Causes of lytic bone lesions in children include benign, malignant, and infectious processes. Here, we present the case of a 3-year-old boy presenting with a lytic bone lesion and surrounding soft tissue mass sent for evaluation of possible malignancy versus osteomyelitis. Biopsy revealed granulomatous osteomyelitis, and subsequent purified protein derivative resulted in 20-mm induration. Lesion cultures eventually identified pan-sensitive Mycobacterium tuberculosis. We emphasize that tuberculosis can cause primary lytic bone lesions in children in the United States, even in the absence of pulmonary symptoms or known exposure, and advise clinicians to include mycobacterial cultures when analyzing biopsies of lytic bone lesions. PMID- 17356404 TI - Autonomous thyroid nodule in an adolescent 10 years after total body irradiation for bone marrow transplant. AB - A male patient with B-cell lymphoma was treated with chemotherapy and allogeneic bone marrow transplant, including preparatory total body irradiation. Ten years later, at age 15 years, the patient developed an autonomous thyroid nodule and an incidental papillary microcarcinoma. This is the first report of an autonomous thyroid nodule after total body irradiation for bone marrow transplant. The case is presented and the literature is reviewed. PMID- 17356405 TI - Diagnostic difficulties of the hemophagocytic lymphohistiocytosis (HLH) associated with the Epstein-Barr virus. PMID- 17356406 TI - RPS19 and JAK2 genes are not silenced by DNA methylation in diamond blackfan anemia. PMID- 17356407 TI - Imatinib-induced dental hyperpigmentation in childhood chronic myeloid leukemia. PMID- 17356408 TI - Contributing to nursing in a new way. PMID- 17356409 TI - Pro: Should parents be present during their child's anesthesia induction? PMID- 17356410 TI - Con: Should parents be present during their child's anesthesia induction? PMID- 17356411 TI - Intimate partner physical and sexual assault & child behavior problems. AB - PURPOSE: To describe the type and extent of child behavior problems reported by mothers who report intimate partner physical and sexual assault compared to mothers who reported physical assault only. STUDY DESIGN AND METHODS: A descriptive analysis of child behaviors, as measured on the Child Behavior Checklist, for 109 children, aged 18 months to 18 years, who were exposed to intimate partner physical and sexual assault. Multivariate analysis of variance and analysis of variance were used to determine whether children from physically and sexually assaulted mothers differed significantly in scores from children of physically assaulted only mothers. RESULTS: Scores for youth (n = 21) 12 through 18 years of age of physically and sexually assaulted mothers were significantly higher (M = 61.5, SD = 2.4; p = .025) than scores of youth (n = 10) of physically assaulted only mothers (M = 50.8, SD = 3.5) and higher than scores of clinically referred youth in a treatment sample. Child behavior was associated with the type of violence experienced by the mother; older children were at the highest risk for behavior disorders, especially behaviors of depression and anxiety. CLINICAL IMPLICATIONS: Intimate partner violence assessment of mothers during child health visits is recommended with safety planning and guided referral to community counseling, legal, shelter, and health agencies, along with information on the child behavior problems associated with domestic violence. PMID- 17356414 TI - Repeat pregnancy in adolescence: intentions and decision making. AB - PURPOSE: To determine the perceptions of young mothers concerning their intentions about repeat pregnancy and to determine shared meanings concerning intentionality and decision making about sexual activity and use of birth control. DESIGN AND METHODS: Ethnographic, descriptive study with interviews of a purposive sample of young mothers with a repeat pregnancy. Iterative methods, recursive data sifting, and Ethnograph 5.0 were used in data analysis. RESULTS: All of the mothers stated that their repeat pregnancies were unintended. Regarding decision making about sexual activity, some mothers discussed a conscious, rational decision-making process before sexual activity, whereas others talked about a more impulsive, spontaneous participation in unprotected sexual activity. A key finding in this study was that although mothers did not intend to get pregnant, they also did not intend to prevent pregnancy. Many discussed feeling pressured to have sex, coerced into not using birth control, unable to implement safe sex behaviors, or just "doing it." CLINICAL IMPLICATIONS: These data suggest that much of teen sexual activity is spontaneous, unplanned, and sometimes involuntary. As such, interventions must be created that take the nature of this sexual activity into account. Consideration of young mothers' thought processes, intentions, and perspectives is integral in the design and implementation of programs and policies to prevent or delay repeat pregnancy during the adolescent years. PMID- 17356412 TI - Requesting perinatal autopsy: multicultural considerations. AB - The subject of perinatal autopsy is not frequently seen in the literature. Perinatal loss, particularly stillbirth, frequently remains unexplained, despite current technology and diagnostic procedures. Parents may automatically refuse an autopsy, despite the potentially valuable information it could provide about the current pregnancy and subsequent pregnancies and despite the possible comfort the results could provide for relatives. Other reasons for declining an autopsy could be cultural or religious prohibitions. In addition, healthcare providers sometimes lack the knowledge of circumstances under which a postmortem examination is permitted, and fail to use culturally sensitive and culturally competent discussions about the reasons a postmortem examination is important and permissible. This purpose of this article is to provide information on selected cultural and religious groups to assist the nurse who is seeking consent for a perinatal autopsy. PMID- 17356415 TI - Issues related to delivering an early childhood home-visiting program. AB - PURPOSE: To describe the issues related to delivering an early childhood home visiting program, BabyFirst, from the perspective of public health nurses and lay home visitors (paraprofessionals). STUDY DESIGN AND METHODS: This descriptive, qualitative interpretive study had a sample of 24 public health nurses and 14 lay home visitors. One in-depth, semi-structured, audio-taped interview was conducted with each participant. Transcribed data were analyzed using content analysis techniques. RESULTS: Public health nurses and lay home visitors identified several issues associated specifically with the use of lay home visitors and more broadly with the delivery of the BabyFirst program. These are discussed in the following categories: issues related to (a) the lay home visitors, (b) the BabyFirst families, and (c) the general administration of the program. CLINICAL IMPLICATIONS: Findings from this study provide information about the issues related to providing home-visiting services delivered by lay home visitors that can be applied to policy and practice development. The findings suggest that in addition to careful selection of prospective applicants, considerable resources should be provided in preparing public health nurses and home visitors for their respective roles. The concerns identified by nurses and home visitors suggest the need to target the following three areas: (a) training and retention of nurses and home visitors, (b) program delivery, and (c) enrollment of families. Attention to the issues discussed in this article has implications for improving the BabyFirst home-visiting program and other similar early childhood programs. PMID- 17356416 TI - Picture perfect: benefits and risk of fetal 3D ultrasound. AB - The purpose of this literature review was to survey available information and research related to routine three-dimensional (3D) ultrasound technology in obstetrics, with an emphasis on current medical uses, safety, and availability issues. Several data bases, including Cochrane, WHO, NIH, CINALH, Blackwell Synergy, ERIC, PubMed, and Medline, were used along with information from Internet search engines. Although fetal 3D ultrasound is used in both medical and commercial settings, recent studies focus on its possible uses rather than the more difficult issues of safety and commercial applications. Professional organizations associated with ultrasound technology support limiting ultrasounds in pregnancy to medically necessary events, whereas commercial venues use "direct to consumer" marketing to promote this technology as a way to "see" the baby before it is born. How safe is routine or frequent use of 3D ultrasound? Further research is needed to address these important questions. PMID- 17356418 TI - Smoking too young: students' decisions about tobacco use. AB - PURPOSE: To describe college students' decisions related to tobacco use. STUDY DESIGN AND METHODS: A sample of 49 smokers and 51 nonsmokers were asked about the smoking continuum of starting smoking, continuing to smoke, and tobacco cessation. An investigator-developed questionnaire was used to determine tobacco use and whether prevention and cessation messages were perceived as effective. Data were analyzed using descriptive statistics and qualitative descriptive analysis. RESULTS: Peer pressure was the greatest influencing factor for beginning to smoke, and health was the major reason for not beginning to smoke. Addiction and stress maintained smoking. Both smokers and nonsmokers identified cessation strategies. CLINICAL IMPLICATIONS: Every interaction with youth is another opportunity to assess smoking status. Recommendations from teens for cessation programs identified in this study may be more attractive to teens and young adults than the current standards related to strategies for adults. PMID- 17356419 TI - Intervening to promote early initiation of breastfeeding in the LDR. AB - PURPOSE: To evaluate the effectiveness of an interventional protocol for the early initiation of breastfeeding that would remove barriers in the labor, delivery, recovery (LDR) unit. STUDY DESIGN AND METHODS: Descriptive design using 100 postpartum mothers who were interviewed before discharge at a large university hospital in the south-central United States. Descriptive statistics were used for analysis. RESULTS: The protocol was effective for initiating breastfeeding, and breastfeeding increased from 53% to 66%. CLINICAL IMPLICATIONS: When barriers to breastfeeding are reduced in the LDR setting, women will breastfeed. It is possible that reducing hospital barriers to breastfeeding in the LDR can also set the stage for sustained breastfeeding during hospitalization and for less supplementation with formula. PMID- 17356420 TI - Toddlers: start off on the right foot. PMID- 17356421 TI - Do you know about physiologic monitoring and "smart clothes"? PMID- 17356422 TI - How much does the world value children? PMID- 17356425 TI - Infant nutrition. PMID- 17356435 TI - Kernicterus prevention. PMID- 17356436 TI - From teamwork to team science. PMID- 17356437 TI - Symptom clusters in acute myocardial infarction: a secondary data analysis. AB - BACKGROUND: Early recognition of acute myocardial infarction (AMI) symptoms and reduced time to treatment may reduce morbidity and mortality. People having AMI experience a constellation of symptoms, but the common constellations or clusters of symptoms have yet to be identified. OBJECTIVES: To identify clusters of symptoms that represent AMI. METHODS: This was a secondary data analysis of nine descriptive, cross-sectional studies that included data from 1,073 people having AMI in the United States and England. Data were analyzed using latent class cluster analysis, an a theoretical method that uses only information contained in the data. RESULTS: Five distinct clusters of symptoms were identified. Age, race, and sex were statistically significant in predicting cluster membership. None of the symptom clusters described in this analysis included all of the symptoms that are considered typical. In one cluster, subjects had only a moderate to low probability of experiencing any of the symptoms analyzed. DISCUSSION: Symptoms of AMI occur in clusters, and these clusters vary among persons. None of the clusters identified in this study included all of the symptoms that are included typically as symptoms of AMI (chest discomfort, diaphoresis, shortness of breath, nausea, and lightheadedness). These AMI symptom clusters must be communicated clearly to the public in a way that will assist them in assessing their symptoms more efficiently and will guide their treatment-seeking behavior. Symptom clusters for AMI must also be communicated to the professional community in a way that will facilitate assessment and rapid intervention for AMI. PMID- 17356438 TI - Using a genetic algorithm to predict evaluation of acute coronary syndromes. AB - BACKGROUND: Because rapid therapy can improve the unfavorable prognosis of individuals with acute coronary syndromes (ACSs), it is critical that nurses accurately associate the cues of ACS and quickly and aggressively initiate interventional strategies that reduce mortality. OBJECTIVES: To determine if genetic algorithms (GAs) can be used to decipher the prediction rules that emergency department (ED) nurses use to triage persons suspected of having ACS and to determine whether these rules differ based on patient gender. METHODS: A nonexperimental, descriptive study was conducted. Three thousand ED nurses were selected randomly to receive a mailed clinical vignette questionnaire, and 840 questionnaires were returned. Data analysis included binary logistic regression (BLR), development of GA, sensitivity, specificity, receiver-operator characteristic curves, and Monte Carlo simulations. RESULTS: Nurses use different prediction rules for triaging male and female vignette patients with possible ACS. Accuracies were similar between BLR and GA. Both suffered a loss of predictive accuracy when algorithms or equations developed on one sex were tested on the other sex. Monte Carlo simulations showed that similar cues were used in triaging both men and women but they were combined differently in producing GA. DISCUSSION: Using GA was as accurate as results found by BLR and can be used to predict nurses triage decisions for ACS. The GA presented as flow charts may be user-friendly. PMID- 17356439 TI - Using polytomous item response models to assess death anxiety. AB - BACKGROUND: : The study of human attitudes toward death has given rise to a substantial body of empirical research. Psychometric instruments have been developed to measure fear of death, or death anxiety, and its psychological consequences in people who continually come into contact with stimuli related to mortality. OBJECTIVES: : To analyze the 20-item Death Anxiety Inventory (DAI) within the framework of item response theory (IRT) and using the generalized partial credit model. METHODS: : The sample comprised 154 men and 550 women and was drawn from nurses, doctors, industrial workers, teachers, undergraduates, and retired persons. Subjects completed the DAI, a self-administered, Likert-type questionnaire of 20 items, each with six response options. RESULTS: : The DAI showed a relatively adequate fit to the generalized partial credit model. Thus, 4 of the 20 items presented a poor fit to the model. The analysis of item information and test information functions revealed that the 20-item test was appropriate for differentiating subjects with medium or high levels of death anxiety. The test information function was higher in this range of scores, indicating greater precision in the estimate of death anxiety for these subjects. DISCUSSION: : The generalized partial credit model can be used to obtain detailed information about a clinical test and its items, and there are advantages to this approach when working with polytomous tests. PMID- 17356440 TI - Differences in resident characteristics and prevalence of urinary incontinence in nursing homes in the southeastern United States. AB - BACKGROUND: Relatively little is known about differences in the prevalence of urinary incontinence (UI) by race and region in the United States. OBJECTIVES: To use the 1999-2002 Centers for Medicare and Medicaid Services (CMS) Minimum Data Set (MDS), Atlanta Region, to investigate the prevalence of UI among African American and Caucasian residents of nursing homes (NH) in the southeastern United States. METHODS: A repeated-measures, two time-period design was employed. Data for 95,911 residents in 7,640 NH were extracted using the study's inclusion and exclusion criteria. Residents' admission and annual assessment records were accessed; UI presence and relevant indicators were captured; and admission and postadmission UI prevalence rates were determined by region, state, race, and gender. Logistic regression, adjusting for residents' demographics, morbidity status, bed mobility, and cognitive and functional statuses, was conducted also. RESULTS: The majority of residents were Caucasian (82.4%) and women (76.5%) with mean (+/-SD) age of 82.7 +/- 7.58 years. Regional UI prevalence was 65.4% at admission and 74.3% postadmission. Postadmission, 73.5% of Caucasian and 78.1% of African Americans were incontinent. Similarly, 72.2% of men and 75% of women were incontinent. For African Americans postadmission, adjusted odds of UI were OR = 1.07 (95% CI: 1.01, 1.14). DISCUSSION: Prevalence of UI was high in this region and the odds of UI was significantly higher among African Americans in two of eight states, suggesting racial disparity in this condition in these states. Factors contributing to this disparity should be explored to increase quality care to vulnerable populations. PMID- 17356441 TI - Threat appraisal, coping, and emotions across pregnancy subsequent to perinatal loss. AB - BACKGROUND: Pregnancies after perinatal loss are known to be anxiety-filled. Stress in pregnancy and the response to it, often seen as anxiety and depression, have known negative consequences for obstetric outcomes, parenting, and infant behaviors. Women have reported fluctuating emotions in response to events in their subsequent pregnancies, but these pregnancies have not been studied longitudinally. OBJECTIVES: To test Lazarus' theory of stress, coping, and emotions in this population, and to understand the patterns of threat appraisal, coping, and emotional states of women across pregnancy after perinatal loss. METHODS: In this predictive correlational study, 82 women pregnant after loss (PAL) were followed, and the study was guided longitudinally by Lazarus' theory of stress, coping, and emotions. Obstetric and loss history, and assigned fetal personhood were gathered at intake (Time 1). Measures completed at 10-week intervals (one time each trimester) included Moneyham Threat Index (threat appraisal), Ways of Coping Checklist-Revised (relative coping), Pregnancy Anxiety Scale (pregnancy anxiety), Multiple Affect Adjective Checklist-Revised (emotional states), and Stress in Life (stress). Time 3 sample size was 70. RESULTS: Threat appraisal was correlated with assigned fetal personhood and gestational age of past loss. Pregnancy subsequent to loss was perceived as a threat, and threat appraisal strongly predicted pregnancy anxiety. Pregnancy anxiety, reported at moderate levels on average, decreased over time; threat appraisal, coping, and other emotions were stable across pregnancy. Coping did not mediate these effects, but relative coping was correlated with emotional status as theorized, with problem-focused coping used more than emotion-focused coping. DISCUSSION: Women find pregnancy after loss stressful and a threat, and this appraisal remains across pregnancy. Because pregnancy anxiety is common, and highest in early pregnancy, providers should address worries and fears with all women early in PAL. Interventions must be tested in future studies. PMID- 17356442 TI - Nurses' attitudes toward provision of care and related health outcomes. AB - BACKGROUND: Supportive care during childbirth is as old as humankind and has been a cornerstone of intrapartum practice for decades. Researchers have postulated that supportive care during labor leads to positive outcomes by enhancing normal labor physiology and the mother's childbirth experience. Questions, however, have risen about the ability of intrapartum nurses to provide effective supportive care within today's medicalized hospital birth environment. OBJECTIVES: The aims of this study were to examine the contribution of attitudinal, normative, and control influences on intrapartum nurses' intentions to provide professional labor support (PLS) to parturient women and to assess if behavioral intent could predict the outcome of length of labor. METHODS: A retrospective exploratory study was used to survey 39 registered nurses and 419 nurse-patient dyads to understand the relationship between predictor variables, behavioral intention, and health outcomes. Multiple regression analysis was used for statistical analysis. RESULTS: The Theory of Planned Behavior (TPB) explained 70% of the variance in intrapartum nurses' intentions to provide PLS to their patients. Behavioral intent (beta = -.08, rho =.677) had no statistically significant impact on a patient's length of labor. DISCUSSION: Both attitude and social pressures had a significant impact on the intention to perform PLS, and results show the relative importance of these variables in understanding the nurse's intention to provide support. Although behavioral intent had no significant influence on behavior, as measured by the patient's length of labor, clinical significance needs to be addressed. The regression correlation suggested that as the behavioral intent scores increased, length of labor decreased in the nurse's parturient population. Further studies are required to determine if the TPB can predict health outcomes through nurses' intentions to provide care. PMID- 17356443 TI - Self-care management and risk factors for depressive symptoms among Taiwanese institutionalized older persons. AB - BACKGROUND: Depression in the elderly has become a serious healthcare issue worldwide, but studies of self-care strategies and risk factors for depressive symptoms are limited. OBJECTIVES: To determine the self-care strategies and risk factors for depressive symptoms among residents of public elder care homes in Taiwan. METHODS: A cross-sectional design was used. Two of 18 public elder care homes were chosen by random sampling throughout Taiwan. Residents (N = 200) of these two care homes who were 65 years old or above and without severe cognitive deficit participated in this study. RESULTS: Nearly half of the participants (49%) were identified by the Geriatric Depression Scale as depressed. Most participants (93%) used self-care strategies to manage their depressive symptoms. The most frequently used strategy was "take a walk." Self-learning was the main information source for self-care strategies. Logistic regression analysis indicated that cognitive function, perceived health status, and osteoarthritis were significant predictors of depression in this sample. CONCLUSIONS: Because older persons tended to engage in activities and to interact with others to manage their depressive symptoms, healthcare providers in public elder care homes may consider arranging enough activities and people contacts for residents. Due to the limited number of healthcare providers in these homes, the author recommends increasing the knowledge of both providers and residents about depression and self-care management strategies. PMID- 17356444 TI - Methods to optimize recruitment and retention to an exercise study in Chinese immigrants. AB - BACKGROUND: To counter pervasive disparities in healthcare and guide public health prevention programs, culturally sensitive recruitment and retention strategies for Chinese immigrants participating in health-related research studies are needed. OBJECTIVES: The aim of this study was to develop and implement recruitment and retention strategies with Chinese immigrants in a Tai Chi exercise study. METHODS: After substantial project planning and incorporating community-based research principles, a multidimensional approach was used to ensure minimal loss to follow-up. Recruitment strategies included partnering with a community-based agency, distributing study information using a multimedia approach, communicating in the native language, and demonstrating cultural sensitivity. Retention strategies included establishing a tracking method during recruitment, providing personalized feedback, maintaining the same location for all aspects of the study, eliminating potential linguistic barriers, providing personal attention and encouragement, monitoring attendance, utilizing a charismatic Tai Chi instructor, respecting Chinese culture, providing appropriate incentives, and maintaining good communication. RESULTS: Sixty persons showed interest in the study, 52 persons were screened, and 39 persons were enrolled. Recruitment was completed within 3 weeks. An advertisement in the Chinese newspaper was the most fruitful recruitment source, yielding approximately 60% of the study participants. Retention in the study was also very high (97%, n = 38). DISCUSSION: The successful recruitment and retention of Chinese immigrants in this Tai Chi exercise study are due to a variety of factors on many levels, including the participants, study investigator, and community-based agency. PMID- 17356447 TI - Where nursing knowledge comes from. PMID- 17356445 TI - Co-bedding twins: how pilot study findings guided improvements in planning a larger multicenter trial. AB - BACKGROUND: Co-bedding, a developmental care practice for twins and multiples, has been theorized as a strategy to decrease the adverse neurodevelopmental effects that may be associated with hospitalization. OBJECTIVE: The aim of this study was to determine the feasibility of study design, methods, and the measurement of desired outcomes for the development of a larger multicentered study. RESULTS: Study findings were used to estimate effect size, determine staff and bedside care organization, evaluate feasibility of data collection measures, and identify issues related to recruitment and follow-up. Results were incorporated in the development of a larger multicentered trial grant proposal. DISCUSSION: Pilot studies can play an important role in the development of a competitive grant proposal and efficient conduct of a research trial. Pilot studies strengthen a proposal by providing essential baseline information. A general overview of the purpose of pilot studies is provided here, along with a description of the process of using findings from a pilot study to inform the development of a larger multisite trial. Findings from this pilot study examining the effects of co-bedding on twins and their parents are used to revise the research protocol for a larger multisite trial. These changes, which lead to improvement to the protocol, and the rational for these changes are highlighted. PMID- 17356449 TI - Bariatric and body-contouring surgery: a continuum of care for excess and lax skin. AB - Obesity continues to reach epidemic proportions in the United States, with more than 60% of Americans classified as obese. Correspondingly, the number of individuals undergoing bariatric surgery has increased dramatically. There are several bariatric procedures that may be performed, with laparoscopic adjusted gastric band (LABG) the newest. Following bariatric surgery and massive weight loss, patients may be left with problematic loose, hanging skin. The loose or redundant skin may occur on the abdomen, back, upper arms, and inner and outer thighs. Body-contouring surgery may be performed to correct the residual excess tissues. Prebariatric planning for plastic surgery to correct skin defects, as well as postoperative bariatric and body-contouring care, is discussed. PMID- 17356451 TI - Effect of breast augmentation mammoplasty on self-esteem and sexuality: a quantitative analysis. AB - Although not extensively researched, psychologic factors have attributed to the growing number of performed breast augmentation procedures. The reported a 293% increase in the cases of cosmetic surgery since 1997. The percent increase in breast augmentation procedures performed in 2003 was up 12 (280 procedures up to 401). As the number of women seeking breast augmentation surgery continues to rise, an increasing number of healthcare professionals are likely to be confronted with questions, concerns, and complications that often accompany the procedure. Consequently, it is important that healthcare providers comprehend the degree to which self-esteem and/or sexuality may affect their patients' outcomes. Healthcare professionals must ascertain specific nursing skills and attitudes while caring for the cosmetic surgical patient. Therefore, the purpose of this research is to gain an understanding of the changes that occur in the levels of self-esteem and sexuality following the breast augmentation. Test of the study hypotheses 1 through 4 failed to be rejected, thereby supporting significant positive relationships between the variables. Statistical analysis of Hypothesis 5 found positive significance between breast augmentation, self-esteem, and the demographic variables-educational level and history of previous cosmetic surgery. PMID- 17356452 TI - Internet resources for evidence-based practice in nursing. AB - There are many Web sites where nurses can find valuable information on evidence based practice. This brief article reviews some of those Web sites and includes Internet resources for learning about evidence-based nursing and finding evidence to guide nursing practice. PMID- 17356453 TI - Hand hygiene-meeting the JCAHO safety goal: can compliance with CDC hand hygiene guidelines be improved by a surveillance and educational program? AB - While establishing 2004 department goals, the new JCAHO Safety Goal of improving compliance with CDC hand washing recommendations was an appropriate department initiative for a hospital Wound Care Center. The purpose of the project was to improve physician compliance with hand hygiene. Nursing staff monitored physician hand washing and provided a compliance report to each physician. Informative articles pertaining to hand hygiene were provided to each physician. Follow-up monitoring demonstrated a significant increase in physician compliance with an additional benefit of patients showing interest in hand hygiene. Continuous oversight of hand hygiene may ultimately reduce the incidence of infection transmission. PMID- 17356454 TI - Now is the time...to plan for workplace emergencies and evacuations! PMID- 17356455 TI - Documentation risk management. PMID- 17356456 TI - Arnica. PMID- 17356461 TI - Steri-strip S surgical skin closures. PMID- 17356462 TI - HIPAA review and update 2006-2007. PMID- 17356463 TI - Ex vivo effect of estrogen and progesterone compared with dexamethasone on cell mediated immunity of HIV-infected and uninfected subjects. AB - To define the effect of estrogen and progesterone concentrations achieved during hormonal contraceptive therapy (HCT) on cell-mediated immunity (CMI) of HIV infected and uninfected subjects, peripheral blood mononuclear cells (PBMCs) from varicella-zoster virus (VZV)-seropositive individuals were treated with 0.1 ng/mL of estradiol, 33 ng/mL of norgestrel, and 13 ng/mL of dexamethasone and tested for VZV CMI. Estrogen and progesterone decreased VZV lymphocyte proliferation and T helper (Th) 1/inflammatory cytokine secretion, albeit less than dexamethasone. Progesterone decreased the expression of CD69 activation marker on CD8 and CD14 cells and increased the expression of Fas ligand (CD178) on CD14 monocytes, suggesting that induction of apoptosis may contribute to the inhibitory effect of this hormone. Cytokine production of separated CD4, CD8, and CD14 cells confirmed the effect of progesterone on all 3 cellular types, whereas the effect of estrogen was restricted to CD14 monocytes. The estrogen- and progesterone mediated inhibition of Th1/inflammatory cytokines was greater in HIV-infected subjects (35% decrease for both hormones) compared with uninfected subjects (12% and 19% for estrogen and progesterone, respectively), whereas the effect on proliferation and PBMC phenotype did not differ by HIV status. Overall, HCT concentrations of estrogen and progesterone downregulated ex vivo VZV CMI of HIV infected and uninfected subjects. PMID- 17356464 TI - Identification of 3 phylogenetically related HIV-1 BG intersubtype circulating recombinant forms in Cuba. AB - BG intersubtype recombinants represented 11.6% of HIV-1 isolates in a recent survey in Cuba based on pol sequences, most of them forming a single clade further subdivided into 3 subclades. Here, we analyze 8 near full-length genomes and 1 gag-pol sequence from epidemiologically unlinked Cuban BG recombinants from these 3 subclades (3 from each). Near full-length sequences were also obtained from 3 subtype G and 2 subtype B Cuban viruses. Phylogenetic relationships were estimated via maximum likelihood, and mosaic structures of the recombinants were inferred with the bootscanning, MaxChi, Genconv, and GARD methods. For the near full-length genomes, all recombinants formed a strongly supported clade further subdivided into the same subclades previously defined in pol. Mosaic structures were identical within each subclade and different among subclades, although 5 breakpoints were coincident among all recombinants. Individual phylogenetic trees for nonrecombinant fragments (concatenated B and G subtype segments) indicated a common ancestry for the parental viruses and their relationships to local subtype B and G strains. These results allow us to identify 3 new BG intersubtype circulating recombinant forms in Cuba derived from a common recombinant ancestor, which originated from B and G subtype parental strains circulating in Cuba. PMID- 17356465 TI - Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. AB - OBJECTIVE: Although highly active antiretroviral therapy (HAART) can reverse HIV related neurocognitive impairment (NCI), neuropsychologic (NP) deficits may persist in a substantial proportion of patients despite antiretroviral treatment. We assessed the prevalence and predictors of persistent NP deficits despite long term HAART in patients with HIV-related NCI. METHODS: A group of 94 patients with HIV-related NCI underwent 2 to 7 serial NP batteries, neurologic examination, and brain imaging studies. Patients received HAART for a mean of 63 (range: 6-127) months. According to NP assessment results, patients were considered to have reversible or persistent NP deficits. Kaplan-Meier analyses and Cox proportional hazards models were used to analyze time to first evidence of NP deficit reversion. RESULTS: Persistent NP deficits were observed in 59 (62.8%) patients. Age, gender, Centers for Disease Control and Prevention stage, risk category, CD4 cell count, plasma viral load, and use of central nervous system-penetrating drugs were not associated with persistent NP deficits. By contrast, patients with persistent NP deficits were less educated and showed poorer baseline performances in NP measures exploring concentration and speed of mental processing, memory, and mental flexibility. In multivariable analyses, only the baseline severity of NCI, as measured by the composite NPZ8 global score (odds ratio = 3.07, 95% confidence interval: 1.54 to 6.08; P = 0.001) remained significantly associated with persistent NP deficits. CONCLUSIONS: The severity of NCI at HAART initiation seems to be the strongest predictor of persistent NP deficits despite long-term HAART. Our data indicate that HAART should be initiated as soon as NCI is diagnosed to avoid potentially irreversible neurologic damage. PMID- 17356466 TI - Association between hepatitis C virus coinfection and regional adipose tissue volume in HIV-infected men and women. AB - OBJECTIVE: Coinfection with hepatitis C virus (HCV) is reported to be associated with a higher prevalence of lipodystrophy than HIV infection alone. We examine the association between HCV and adipose tissue volume in HIV-infected men and women. METHODS: Cross-sectional analysis of HIV-infected subjects from the study of Fat Redistribution and Metabolic Change in HIV Infection. MRI measured regional adipose tissue volume. Detectable HCV RNA defined HCV infection. RESULTS: Twenty percent of 792 men and 26% of 329 women were HIV/HCV-coinfected. HIV/HCV-coinfected and HIV-monoinfected women had similar amounts of subcutaneous adipose tissue (SAT) in the leg, lower trunk, upper trunk, and arm and similar amounts of visceral adipose tissue (VAT). Similar findings were seen in men, except in the leg and VAT. After adjustment, HCV infection remained associated with more leg fat in men (12.2%, 95% confidence interval [CI]: 0.3 to 25.3; P = 0.043). Among those on stavudine, HIV-monoinfected men had less leg fat (-7% effect per year of stavudine use, 95% CI: -9 to -5; P < 0.001); a weaker association was seen in HIV/HCV-coinfected men (-2% effect, 95% CI: -7 to 3; P = 0.45). Indinavir was associated with less leg fat (-4% in HIV-monoinfected men, 95% CI: -6 to -1; P = 0.002; -5% in HIV/HCV-coinfected men, 95% CI: -11 to 2; P = 0.14). CONCLUSIONS: Our findings suggest that HIV/HCV coinfection is not associated with less SAT in men and women. HCV infection seems to mitigate the loss of leg fat seen in HIV-infected men on stavudine. PMID- 17356467 TI - Proinflammatory and type 1 cytokine expression in cervical mucosa during HIV-1 and human papillomavirus infection. AB - Suppression of immune activation and increased inflammation are prevalent during viral infection. To investigate the role of inflammation in HIV transmission, we studied the infectious and inflammatory milieu in cervical mucosa from HIV-1- and human papillomavirus (HPV)-coinfected and HPV-monoinfected women. The numbers of cytokine-, chemokine-, and p24-expressing cells were determined using in situ imaging analysis and intracellular staining of p24 antigen. Significantly higher expression of the proinflammatory cytokines, interleukin (IL)-1alpha/beta, was seen in cervical tissue from HIV/HPV-coinfected as compared with HPV-monoinfected tissues, whereas IL-2- and interferon (IFN)-gamma-expressing cells were higher in HPV-monoinfected tissues. IL-10 was low in both groups, whereas IL-4 was significantly higher in HPV-monoinfected and HIV/HPV-coinfected tissues than in HIV/HPV-negative controls. RANTES and macrophage inflammatory protein (MIP)-1beta but not MIP-1alpha were significantly higher in the genital tract of HIV/HPV coinfected as compared with HPV-monoinfected individuals and controls. HIV/HPV coinfected tissues had a higher level of human leukocyte antigen D-related (HLA DR)-expressing dendritic cells (DCs). There was a positive correlation between the number of CD4(+) and CD8(+) T cells as well as CD1a, IL-1alpha, and RANTES expression and p24 antigen-expressing cells in the HIV/HPV-coinfected tissues. These findings suggest the persistence of immune activation and inflammation in the genital tract of women with HPV monoinfection and in HIV-infected women coinfected with HPV. PMID- 17356468 TI - Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6 G516T polymorphism. AB - BACKGROUND: The CYP2B6-G516T polymorphism has been shown to alter plasma efavirenz (EFV) concentrations in adults. The impact of CYP2B6-G516T polymorphisms on EFV concentrations may be different in children because of differences in liver maturation and drug dosage. METHODS: The CYP2B6-G516T polymorphisms were analyzed in 71 HIV-1-infected children receiving highly active antiretroviral therapy (HAART) containing EFV for >or=6 months. EFV pharmacokinetics, toxicity profiles, and viral resistance data were also evaluated. RESULTS: The median oral clearance (CL/F) rate was significantly lower in children with the CYP2B6-516-T/T genotype (3.0 L/h/m2, n=13) than in children with the G/T genotype (5.7 L/h/m2, n=30; P=0.02) or the G/G genotype (7.0 L/h/m2, n=31; P=0.003). In children with the CYP2B6-516-G/G genotype, which is associated with higher expression of hepatic CYP2B6, the clearance rate was significantly higher in younger children (<5 years of age) than in older children (>or=5 years of age) (9.7 L/h/m2 vs. 6.6 L/h/m2; P=0.03). No association was found between CYP2B6-G516T polymorphisms and virologic or immunologic responses, toxicity, or the development of viral resistance against EFV. CONCLUSIONS: CYP2B6-G516T polymorphisms significantly affect the CL/F rate of EFV in children. Changes in hepatic enzyme activity by age may need to be considered when evaluating the impact of genetic variants on antiretroviral pharmacokinetics in children. PMID- 17356469 TI - Prospective screening for human leukocyte antigen-B*5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population. AB - The association of human leukocyte antigen-B*5701 with abacavir hypersensitivity varies depending on ethnic origin. We confirmed the high specificity of B*5701 in the ethnically mixed French population and used a rapid and inexpensive polymerase chain reaction strategy to evaluate the predictiveness of B*5701 screening. The incidence of hypersensitivity decreased from 12% before screening to 0% after screening, and the rate of unwarranted interruptions of abacavir therapy decreased from 10.2% to 0.73%. We therefore recommend the implementation of this cost-effective screen before treatment with abacavir. PMID- 17356470 TI - Early response to highly active antiretroviral therapy in HIV-1-infected Kenyan children. AB - OBJECTIVES: To describe the early response to World Health Organization (WHO) recommended nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first line highly active antiretroviral therapy (HAART) in HIV-1-infected Kenyan children unexposed to nevirapine. DESIGN: Observational prospective cohort. METHODS: HIV-1 RNA level, CD4 lymphocyte count, weight for age z score, and height for age z score were measured before the initiation of HAART and every 3 to 6 months thereafter. Children received no nutritional supplements. RESULTS: Sixty-seven HIV-1-infected children were followed for a median of 9 months between August 2004 and November 2005. Forty-seven (70%) used zidovudine, lamivudine (3TC), and an NNRTI (nevirapine or efavirenz), whereas 25% used stavudine (d4T), 3TC, and an NNRTI. Nevirapine was used as the NNRTI by 46 (69%) children, and individual antiretroviral drug formulations were used by 63 (94%), with only 4 (6%) using a fixed-dose combination of d4T, 3TC, and nevirapine (Triomune; Cipla, Mumbai, India). In 52 children, the median height for age z score and weight for age z score rose from -2.54 to -2.17 (P<0.001) and from 2.30 to -1.67 (P=0.001), respectively, after 6 months of HAART. Hospitalization rates were significantly reduced after 6 months of HAART (17% vs. 58%; P<0.001). The median absolute CD4 count increased from 326 to 536 cells/microL (P<0.001), the median CD4 lymphocyte percentage rose from 5.8% before treatment to 15.4% (P<0.001), and the median viral load fell from 5.9 to 2.2 log10 copies/mL after 6 months of HAART (P<0.001). Among 43 infants, 47% and 67% achieved viral suppression to less than 100 copies/mL and 400 copies/mL, respectively, after 6 months of HAART. CONCLUSION: Good early clinical and virologic response to NNRTI based HAART was observed in HIV-1-infected Kenyan children with advanced HIV-1 disease. PMID- 17356471 TI - Hematologic effects of maternal antiretroviral therapy and transmission prophylaxis in HIV-1-exposed uninfected newborn infants. AB - OBJECTIVE: A prospective observational study to investigate hematologic alterations during the first 3 months of life in HIV-exposed uninfected infants subjected to antiretroviral medication before and after birth. METHODS: Two hundred twenty-one consecutive uninfected infants born to HIV-positive mothers on antiretroviral medication during pregnancy were included. Perinatal transmission prophylaxis comprised zidovudine (ZDV) administered intravenously intrapartum and 10 days after birth. Blood counts and differentials were determined at birth and at 2, 4, 6, and 12 weeks of age, and hematologic toxicity was graded according to pediatric toxicity scales. Data were analyzed according to the kind of prenatal medication (ZDV alone or with another nucleoside reverse transcriptase inhibitor [NRTI] vs. highly active antiretroviral therapy [HAART]). RESULTS: Median hemoglobin was significantly lower in HAART-exposed newborns from birth (P = 0.004) until day 28. During follow-up, 119 (53.8%) infants had anemia grade 2 or higher on at least 1 occasion; 16 (7.2%) received red blood cell transfusion at 23 (range: 1-56) days of age. Neutropenia grade 2 or higher occurred in 106 (48.0%) infants at least once; 8 infants had staphylococcal infections, and 2 infections were severe. After adjustment for possible confounders (prematurity, birth weight, ethnicity, gender, duration of maternal antiretroviral therapy, maternal Centers for Disease Control and Prevention stage, and maternal illicit drug use), HAART exposure was the only independent risk factor for anemia (odds ratio [OR] = 2.22, 95% confidence interval [CI]: 1.06 to 4.64; P = 0.034) and neutropenia (OR = 2.15, CI: 1.02 to 4.55; P = 0.045). CONCLUSIONS: Antiretroviral transmission prophylaxis is associated with significant anemia and neutropenia in HIV-uninfected infants during the first 3 months of life. Anemia was more profound in HAART-exposed infants. PMID- 17356472 TI - The effect of acids on the survival of HIV during drug injection. AB - BACKGROUND: HIV epidemics around the world have been linked to injection drug use. In many instances, the injected drugs are acidic. HIV-1 is known to be labile to acids, but its susceptibility to acids in the conditions in which illicit drugs are injected is unknown. METHODS: We have combined data from ethnographic studies of injection drug use practices with laboratory virology to replicate and evaluate the effects of exposure to acids that are experienced during drug preparation and injection on HIV-1 viability. RESULTS: Short exposures to the acids significantly reduced the likelihood of recovering viable HIV-1 once pH is reduced to 2.3, but acidic solutions did not totally eliminate infectious HIV-1 that might contaminate syringes or solutions being injected, even at the lowest pH tested (pH 1.7). CONCLUSIONS: Acidification of drugs, which is required for dissolving free-base formulations of drugs, can significantly reduce but not eliminate the likelihood that syringes previously used by HIV-1 infected injection drug users infect the next injector. Methamphetamines, which are manufactured under extremely acidic pHs, are unlikely to harbor viable HIV if stored or sold in contaminated injection equipment. PMID- 17356473 TI - [Epidemiology of mental diseases in the elderly]. PMID- 17356474 TI - [The role of stress in the beginning of delayed and early depression in elderly subjects]. PMID- 17356475 TI - [Bipolar disorder and aging]. PMID- 17356476 TI - [Beneficial effect of moderate stress in young age on the aging, longevity and resistance to heat in drosophila fly Drosophila melanogaster]. PMID- 17356477 TI - [The consequences of the changing environment in mental illness]. PMID- 17356478 TI - [Neuro-psycho-immunology: the influence of aging on the biological mechanisms of stress, anxiety and depression]. PMID- 17356479 TI - [Specifics of psychotherapy for anxiety in the aged]. PMID- 17356480 TI - [Aging and pathological stress: could psychotropic drugs be true therapeutic allies?]. PMID- 17356481 TI - [Behavioral and cognitive aspects of stress in the aged]. PMID- 17356482 TI - [Aspects of posttraumatic stress in the aged]. PMID- 17356483 TI - [Stress and family: a necessary place of a dangerous connection?]. PMID- 17356484 TI - [From young to old age: an evolving proof of environmental stress. Clinical perspectives in pediatric and gerontological psychiatry]. PMID- 17356485 TI - [Depression, stress and coronary diseases in the aged]. PMID- 17356486 TI - [Vascular depression: important and limited issues of the concept]. PMID- 17356487 TI - [Psychological aspects of re-education after accidental falls]. PMID- 17356488 TI - [Anxieties and refusal to eat]. PMID- 17356489 TI - [Alzheimer's disease, hippocampus and neuroimaging]. PMID- 17356490 TI - [Stress and imaging of the hippocampus in the aged]. PMID- 17356491 TI - [Stress, Alzheimer's disease and psychotherapy]. PMID- 17356492 TI - [Distress and mental restoration]. PMID- 17356493 TI - [Stress and mental management in the early memory disorders]. PMID- 17356494 TI - [Sudden depression due to dependence and the future of aged hospitalized patients]. PMID- 17356495 TI - [Stress over improbable dementia]. PMID- 17356496 TI - [Recreation in music]. PMID- 17356497 TI - [Cooperation between geriatric psychiatry and geriatrics: the model developed in Geneva]. PMID- 17356498 TI - [Non-pharmacological reality in the treatment of schizophrenia]. PMID- 17356499 TI - [Schizophrenia: a necessary re-consideration of care]. PMID- 17356500 TI - [Psychosocial therapies of schizophrenia: an experience at the Corentin Celton hospital]. PMID- 17356501 TI - [The use of atypical antipsychotics in the long-term care of schizophrenia]. PMID- 17356502 TI - [The evaluation of long-term treatment with antipsychotics]. PMID- 17356503 TI - [Therapeutic observation: an essential objectivity]. PMID- 17356504 TI - Medical simulation in anesthesiology training. AB - Simulators are more and more widely used in different scientific areas. Through very sophisticated and realistic simulations, they actually permit to teach and demonstrate theoretical or practical notions. Besides, they allow to evaluate a particular performance. In the latest years, the use of simulators has considerably developed in medicine. Anaesthetists have been the first to use and develop simulation. Having the possibility to deal with emergencies and getting accustomed to them without any real risk is an undeniable advantage. Even though the long-term effects due to a simulation session haven't been properly evaluated yet, it is important to bear in mind that simulators are being successfully used in an impressive number of centres in different parts of the world. The activities in the medical simulation centres deal to a certain extent with studying and teaching to manage critical events. This particular discipline, deriving from the aeronautic field, relies upon decision making and teamwork in order to manage the critical event most appropriately. Formative trainings, initially meant for anaesthetists and later on open to other medical categories as well, have been developed. Such courses aimed at establishing the proper interactions between different people with different tasks who are involved in the approach to an emergency rather than the management of the whole scenario. The main drawback of simulation is, however, the high costs required to set a simulation programme, especially as far as the human resources involved are concerned. PMID- 17356505 TI - Laryngeal mask in prone position: pure exhibitionism or a valid technique. AB - AIM: The laryngeal mask airway (LMA) is used worldwide during general anesthesia with controlled or spontaneous breathing. Normally its use is limited to patients undergoing surgery in the supine but not the prone position. METHODS: A prospective study of 50 consecutive ASA 1 and 2 patients who underwent ambulatory surgery in the prone position. In the first 25 patients anesthesia was induced in the supine position on a transport trolley after which the patients were turned face down following tracheal intubation. The next 25 patients were asked to lie comfortably in the prone position before receiving anesthesia. Induction and insertion of LMA were performed when they were already prone. RESULTS: There were neither complications nor airway loss when LMA was used in the prone position. The induction-incision time was 23.6+/-3.6 min (range 21-37) in Group 1 and 7+/ 2.44 min (range 5-15) in Group 2 (P<0.0001) and the manpower required for positioning (the number of medical and paramedical personnel required to place the patient prone) was considerable reduced in Group 2 (LMA) compared to Group 1 (1.0 versus 3.12+/-0.6 (range 2-4; P<0.0001). Group 2 showed also, significantly more favorable hemodynamic parameters. CONCLUSION: To start anesthesia with patients already prone shortens the induction-incision time, reduces the manpower involved in the positioning process and causes fewer hemodynamic changes than the standard technique of induction and intubation in the supine position followed by turning the patient facedown. PMID- 17356506 TI - State entropy and bispectral index: correlation with end tidal sevoflurane concentrations. AB - AIM: Aim of this study was to evaluate the difference between the correlations of state entropy (SE) and bispectral index (BIS) with different end tidal concentrations (Et) of sevoflurane. METHODS: A total of 40 ASA I/II patients submitted to abdominal surgery were enrolled in the study. After premedication with fentanyl, anesthesia was induced with propofol and atracurium and maintained with sevoflurane in oxygen and air. The values of Et sevoflurane, SE and BIS were recorded during the operating room stay. The mean Et sevoflurane was calculated and the correlations of SE and BIS with Et sevoflurane were determined with Pearson test separately at values of Et sevoflurane below and higher the mean Et sevoflurane. Student's t-test was used to verify if the difference between the correlations was significant (P<0.05). RESULTS: The mean Et sevoflurane was 1.5%. During anesthesia the correlation with Et sevoflurane was -0.75 for SE and -0.70 for BIS. At Et sevoflurane higher than 1.5% the correlation with Et sevoflurane was -0.41 for SE and -0.14 for BIS. At Et sevoflurane below 1.5% the correlation with Et sevoflurane was -0.65 for SE, and -0.8 for BIS. The difference between the correlations of Et sevoflurane with SE and BIS resulted statistically significant. CONCLUSION: During sevoflurane anesthesia SE shows a better correlation than BIS with Et sevoflurane. Although at low Et sevoflurane the correlation is better with BIS, at high Et sevoflurane the correlation is better with SE. PMID- 17356507 TI - One-day surgery for acquired forefoot deformity: sciatic nerve blockade with mepivacaine vs mepivacaine+ropivacaine: a prospective, randomized study. AB - AIM: The aim of the study was to determine the doses of ropivacaine combined with mepivacaine for sciatic nerve blockade to enable the extension of analgesia without prolonged motor blockade, for the management of very painful operations in one-day surgery. METHODS: After obtaining approval by the ethics committee and written informed consent, we recruited 30 ASA I-III patients undergoing corrective orthopedic surgery of the forefoot in one-day surgery with sciatic nerve blockade. The patients were randomly divided into 3 groups: one control group, treated by 1.5% mepivacaine (300 mg), and two groups differentiated by the dose of 0.5% ropivacaine (25 and 40 mg) used in combination with 1.5% mepivacaine (225 mg). The offset data of the blockade were obtained by a self-assessment form filled in by the patients, and a direct check on discharge by a blinded observer. RESULTS: There was no significant difference in the duration of the blockade among the 3 groups; the extension of analgesia was significant (P<0.003) in the group treated by mepivacaine+ropivacaine 40 mg (mean 477+/-255 min). CONCLUSION: Adequate doses of ropivacaine added to mepivacaine for peripheral blockade produce and increase the duration of analgesia without influencing the criteria for discharge after Day Surgery. PMID- 17356508 TI - Osteoporotic vertebral compression fracture pain (back pain): our experience with balloon kyphoplasty. AB - AIM: The aim of this study is to evaluate the safety and effectiveness of antalgic and functional results after interdisciplinary approach and treatment of vertebral compression fractures (VCF) with percutaneous balloon kyphoplasty (KP) by the pain medicine specialist. METHODS: Between April and December 2004, after informed consent, 13 patients have been treated for a total amount of 15 KP. For L5 - T11 level spinal anesthesia was performed, above T11 local infiltration was used. The following parameters were recorded: intraoperative course, postoperative course, pain before and after treatment, vertebral height restoring and quality of life measuring on visual analogical scale (VAS) and quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) scale. RESULTS: No complications or adverse events were recorded. VAS values for pain were 6.2+/-2.1 preKP vs 3.3+/-1.7 and 4.5+/-1.1 respectively postKP and at follow up, with statistically significant differences. Vertebral heights were 53.5+/ 16%, 71.2+/-21% and 68.1+/-13.5%, preKP, postKP and at follow-up respectively, with statistically significant differences, similarly to quality of life related parameters and QUALEFFO score. CONCLUSION: Back pain due to vertebral compression fractures is a quite frequent diagnosis for the pain medicine specialist; KP is a new technique showing an association of a low incidence of complications with a success rate, both on pain control and on vertebral height restoring. In our study, KP proved to be a safe technique with a high success rate, both for pain relief and for vertebral height restoring, with immediate results and important consequences on the patient's quality of life, physical and mental status, with a low incidence of complications due also to the choice of performing this procedure in locoregional anesthesia. PMID- 17356509 TI - Considerations, meditations and doubts of an anesthesiologist regarding the enigma of the mind, consciousness, and awareness of the self. PMID- 17356510 TI - Characterization of human corneal stem cells by synchrotron infrared micro spectroscopy. AB - PURPOSE: The purpose of this study was to use high resolution synchrotron radiation-based Fourier Transform Infrared (FTIR) micro-spectroscopy coupled with multivariate analysis to investigate the characteristics of adult stem cell (SC) and transit amplifying (TA) cell populations of the human corneal epithelium. METHODS: Spectra of individual SC and TA cells in situ from cryosections of human cornea were collected using a synchrotron micro-spectroscopy facility at Daresbury laboratory, UK. Multivariate analysis and Mann Whitney U tests were used to analyse the spectral data from the SC and TA cell populations. RESULTS: There were marked differences between the median spectra of the two cell populations. This correlated with their level of differentiation and functional specialization. Multivariate (principal component) analysis revealed that the cell populations could be segregated into distinct clusters, with only slight overlap between the two cell types. Significant (p<0.05) spectral differences were found in the spectral regions associated with nucleic acid, protein and lipids. CONCLUSIONS: Synchrotron FTIR micro-spectroscopy together with principal component analysis is able to discriminate between SC and TA cell populations. Our results also suggest a small sub-population of corneal epithelial cells in the SC niche have TA cell-like characteristics. Many of the spectral differences between the SC and TA cell populations relate to differences in nucleic acid conformation. PMID- 17356511 TI - Transscleral diffusion of ethacrynic acid and sodium fluorescein. AB - PURPOSE: One of the current limitations in developing novel glaucoma drugs that target the trabecular meshwork (TM) is the induced corneal toxicity from eyedrop formulations. To avoid the corneal toxicity, an alternative approach would be to deliver TM drugs through the sclera. To this end, we quantified ex vivo diffusion coefficient of a potential TM drug, ethacrynic acid (ECA), and investigated mechanisms of ECA transport in the sclera. METHODS: An Ussing-type diffusion apparatus was built to measure the apparent diffusion coefficient of ECA in fresh porcine sclera at 4 degrees C. To understand mechanisms of ECA transport, we quantified the transscleral transport of a fluorescent tracer, sodium fluorescein (NaF), that has a similar molecular weight but is more hydrophilic compared to ECA. Furthermore, we developed a mathematical model to simulate the transport processes and used it to analyze the experimental data. The model was also used to investigate the dependence of diffusion coefficients on volume fraction of viable cells and the binding of NaF and ECA to scleral tissues. RESULTS: The diffusion coefficients of ECA and NaF in the sclera were 48.5+/-15.1 x 10-7 cm(2)/s (n=9) and 5.23+/-1.93 x 10(-7) cm(2)/s (n=8), respectively. Both diffusion coefficients were insensitive to cell shrinkage caused by ECA during the diffusion experiments and cell damage caused by the storage of tissues ex vivo before the experiments. Binding of ECA to scleral tissues could not be detected. The apparent maximum binding capacity and the apparent equilibrium dissociation constant for NaF were 80+/-5 mM and 2.5+/-0.5 mM (n=3), respectively. CONCLUSIONS: These data demonstrated that ECA diffusion was minimally hindered by structures in the sclera, presumably due to the lack of cells and binding sites for ECA in the sclera. PMID- 17356512 TI - Growth of the human eye lens. AB - PURPOSE: To analyze human lens growth from the accumulation of wet weight as a function of age. METHODS: Wet weights were assembled for over 1,100 human lenses, ranging in age from 6 months prenatal to 99 years postnatal, and were examined using various growth models. Initially, prenatal and postnatal data were examined separately, to determine the growth modes and then all data were fitted to a single equation. RESULTS: Variations in weights due to tissue handling procedures and the unavailability of statistical data for averaged sets precluded the use of >500 values in the present analysis. Regression of age on log lens weight for the remaining 614 lenses indicated that, unlike other species, human lens growth appears to take place in two distinct phases. It was found that asymptotic growth during prenatal life and early childhood generates about 149 mg of tissue in a process, which can be modelled with a Gompertz function. Soon after birth, growth becomes linear, dropping to 1.38 mg/year, and this rate is maintained throughout the rest of life. The relationship of lens wet weight with age over the whole of the lifespan could best be described with the expression, W=1.38A(b) + 149exp;[exp;(1.6-3A(c))], where W is lens weight in mg, A(b) is postnatal age in years and A(c) is the time since conception in years. Comparison of 138 male and 64 female lenses indicated that there was no statistically significant difference between male and female lens weights in the linear (adult) growth mode. CONCLUSIONS: Human lens growth differs from growth in other species in that it occurs in two distinct modes. The first follows a sigmoidal relationship and provides an initial burst of rapid growth during prenatal development with an apparent termination at or shortly after birth. The second growth mode is linear, adding 1.38 mg/year to lens wet weight, throughout life. Because of the variability in available lens wet weight data, further studies, preferably using lens dry weights or protein contents, will be required to establish precisely when the transition from one growth mode to the other occurs. In contrast to previous reports, it was concluded that, like other species, there are no gender differences in human lens weights. PMID- 17356513 TI - Retinal pathology and skin barrier defect in mice carrying a Stargardt disease-3 mutation in elongase of very long chain fatty acids-4. AB - PURPOSE: Autosomal dominant Stargardt disease-3 (STGD3) is caused by mutations in elongase of very long chain fatty acids-4 (ELOVL4). The goal of this study was to generate and characterize heterozygous and homozygous knockin-mice that carry a human STGD3 pathogenic mutation in the mouse Elovl4 gene. METHODS: Recombinant Stgd3-knockin mice were generated using a DNA construct which introduced a pathogenic five-base pair deletion and two point mutations in exon 6 of the Elovl4 gene. Stgd3-mouse genotypes were confirmed by Southern blot analysis and expression of wild-type (wt) and mutated Elovl4 mRNAs assayed by nuclease protection assay. The retinal phenotype of heterozygous Stgd3 mice was characterized by morphological studies, elecroretinographic (ERG) analysis and assay of lipofuscin accumulation. Homozygous Stgd3 mice were examined for both retinal and gross morphology. They were also analyzed for skin morphology and skin barrier function, and for epidermal lipid content using high performance liquid chromatography (HPLC) combined with mass spectrometry (MS). RESULTS: The Stgd3 allele codes for a truncated mouse Elovl4 protein, which also contains the same aberrant 8-amino acid C-terminus encoded by the human pathogenic STGD3 allele. Heterozygous Stgd3 mice expressed equal amounts of both wt and mutant Elovl4 mRNAs in the retina, showed no significant changes in retinal morphology, but did show accumulation of lipofuscin and reduced visual function. Homozygous Stgd3 mice were born with an expected Mendelian frequency, without any initial gross anatomical or behavioral abnormalities. By 6-12 h postpartum, they became dehydrated and died. A skin permeability assay detected a defect in epidermal barrier function. Homozygous mutant epidermis expressed a normal content of mutated Elovl4 mRNA and contained all four epidermal cellular layers. HPLC/MS analysis of epidermal lipids revealed the presence of all barrier lipids with the exception of the complete absence of acylceramides, the critical lipids for barrier function of the skin. CONCLUSIONS: The generated Stgd3-knockin mice are a genetic model of human STGD3 and reproduce features of the human disease: accumulation of lipofuscin and reduced visual functions. Homozygous Stgd3 mice showed a complete absence of acylceramides from the epidermis. Their absence suggests a role for Elovl4 in acylceramide synthesis, and in particular, a role in the synthesis of the unique very long chain C30-C40 fatty acids present in skin acylceramides. PMID- 17356514 TI - Defects in retinal pigment epithelium cell proliferation and retinal attachment in mutant mice with p27(Kip1) gene ablation. AB - PURPOSE: Little is known about the mechanisms that regulate cell cycle withdrawal of the retinal pigment epithelium (RPE) during development, or about the mechanisms maintaining epithelial cell quiescence in adult retinas. The present study examines the potential role of the negative cell cycle regulator p27(Kip1) in controlling RPE proliferation, using mice with targeted ablation of the p27(Kip1) gene. METHODS: Ocular tissues were obtained from wild-type and p27(Kip1)-null mice at several postnatal ages. Following aldehyde fixation, eyes were processed intact for JB-4 histology and electron microscopy. Alternatively, tissues were removed by manual or enzymatic dissection in order to obtain flat mounts of the RPE attached to either the choroid-sclera or neural retina, respectively. Epithelial flat-mounts were either left unlabeled, in which case melanin pigment provided internal contrast, or labeled with Alexa Fluor 488 phalloidin and propidium iodide to visualize cell boundaries and nuclei, respectively. RESULTS: Morphometric analysis using transverse plastic sections revealed a 96% increase in nuclear density and a 12% increase in thickness (apical to basal) for mutant vs. normal epithelia at postnatal day 35 (P35). These changes were not restricted to central or peripheral regions, and were uncorrelated with focal areas of dysplasia seen in the mutant neural retina. When similar tissues were viewed as flat-mounts, an observed 100% increase in nuclear density was accompanied by only a 46% enhancement in cellular density. This resulted in a larger proportion of multinucleated cells in the nullizygous RPE as compared with the wild-type epithelium (91 versus 47%). Such a pattern was achieved relatively early in development since, at P7 when the increase in RPE nuclear density was essentially complete, cellular density was augmented by only 39%. In addition to these proliferative changes, individual epithelial cells sometimes exhibited structural abnormalities, including an altered cortical actin cytoskeleton and displacement of nuclei from their normal central position. Surprisingly, while the RPE cells of null animals were similar ultrastructurally to those of the wild-type, interdigitation of their microvillous processes with outer segments was incomplete. Quantitative analysis revealed that such areas of detachment characterize, on average, 42% of the nullizygous retina, and that there is little correlation between detachment and neural retina dysplasia from one eye to another. Together with parallel evidence demonstrating a substantial decline in the apparent adhesiveness of mutant retinas relative to the normal tissue, the data is strongly indicative of an altered epithelium-photoreceptor interaction following gene ablation. CONCLUSIONS: The absence of a functional p27(Kip1) gene results in enhanced RPE nuclear division, without a commensurate increase in cell division. Although the mutant epithelium as a whole appears structurally normal, individual cells exhibit cytoskeletal changes and their interaction with the neural retina is compromised. PMID- 17356515 TI - Association of the Asn306Ser variant of the SP4 transcription factor and an intronic variant in the beta-subunit of transducin with digenic disease. AB - PURPOSE: SP4 is a transcription factor abundantly expressed in retina that binds to the GC promoter region of photoreceptor signal transduction genes. We have previously shown that SP4 may be involved in the transcriptional activation of these genes alone or together with other transcription factors such as SP1, neural retina leucine zipper protein (NRL), and cone-rod homeobox gene (CRX). Since mutations in NRL and CRX are involved in inherited retinal degenerations, SP4 was considered a good candidate for mutation screening in patients with this type of diseases. The purpose of this work, therefore, was to investigate possible mutations in SP4 in a cohort of patients affected with different forms of retinal degenerations. METHODS: 270 unrelated probands with various forms of retinal degeneration including autosomal dominant and autosomal recessive retinitis pigmentosa (RP), autosomal dominant and autosomal recessive cone-rod dystrophy (CRD), and Leber's congenital amaurosis (LCA), were screened for mutations in the SP4 gene. Single strand conformation polymorphism (SSCP) analysis was performed on the six SP4 gene exons including flanking regions followed by direct sequencing of SSCP variants. RESULTS: Nine different sequence variants were found in 29 patients, four in introns and five in exons. Many of the probands were previously screened for mutations in the genes encoding the alpha-, beta- and gamma-subunits of rod-specific cGMP phosphodiesterase (PDE6A, PDE6B, PDE6G), the beta-subunit of rod-specific transducin (GNB1), and peripherin/rds (RDS). One group of seven probands of Hispanic background that included five with arRP, one with RP of unknown inheritance (isolate) and 1 with arCRD carried an Asn306Ser mutation in SP4. Of the seven, the isolate case was homozygous and the other 6 heterozygous for the variant. Two arRP and the arCRD probands carried an additional intronic GNB1 variant. DNA from the family members of the arCRD proband could not be obtained, but for the other two families, all affected members and none of the unaffected carried both the SP4 Asn306Ser allele and the GNB1 intronic variant. CONCLUSIONS: If mutations in SP4 do cause retinal degenerative disease, their frequency would be low. While digenic disease with the SP4 Asn306Ser and the GNB1 intronic variant alleles has not been established, neither has it been ruled out. This leaves open the possibility of a cooperative involvement of SP4 and GNB1 in the normal function of the retina. PMID- 17356517 TI - Differential expression of Kir4.1 and aquaporin 4 in the retina from endotoxin induced uveitis rat. AB - PURPOSE: The inwardly rectifying potassium channel protein Kir4.1 and the water channel protein aquaporin-4 (AQP4) have been suggested to play essential roles in the potassium and water homeostasis of the retina. In this study, we investigated the expression of Kir4.1 and AQP4 in the retina during endotoxin-induced uveitis (EIU) in rats. METHODS: EIU was induced in male Wistar rats by intravitreal injection of lipopolysaccharide (LPS). The severity of the EIU was evaluated by clinical and histopathological examination. The expression of Kir4.1 and AQP4 in the retina was detected by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining. RESULTS: In the animal model of EIU, the clinical changes correlated well with the histopathological findings. The inflammation peaked at 24 h and resolved by seven day. After an intravitreal LPS injection, the expression of Kir4.1 in the retina showed a significant decline at both the protein and mRNA levels. In the early stages of EIU, the expression of Kir4.1 mRNA decreased sharply, reaching a minimum at 12 h (31%, p<0.001). It then increased gradually and had partially recovered 14 days after LPS injection (92%, p>0.05). The expression of Kir4.1 protein decreased significantly, reaching a minimum at three days after the LPS injection (43%, p<0.001). Thereafter, it increased slightly but was maintained at a low level until 14 days after LPS injection (64%, p<0.001). In contrast, the expression of AQP4 mRNA remained almost unchanged after LPS treatment (p>0.05). The expression of AQP4 protein was only slightly reduced at one day (82%, p>0.05) after LPS injection and then increased gradually and had nearly recovered to the basal level at 14 days after LPS injection. CONCLUSIONS: EIU differently alters the expression of Kir4.1 and AQP4 in the retina. The differential expression of Kir4.1 and AQP4 during EIU implies a disturbance of water and potassium transport in the retina, which may contribute to the retinal edema during ocular inflammation. PMID- 17356518 TI - Does preparticipation cardiovascular screening of athletes save lives? PMID- 17356516 TI - Microarray reveals complement components are regulated in the serum-deprived rat retinal ganglion cell line. AB - PURPOSE: Glaucoma is a progressive eye disease that leads to blindness due to loss of retinal ganglion cells (RGCs). There are difficulties in using primary cultures of purified RGC to study this pathophysiology. RGC-5, a transformed not RGC line, expresses several markers characteristic of the RGCs. The aim of this study was to generate a genome-wide gene expression of RGC-5 following serum deprivation and to identify candidate genes that may be involved in the signal transduction pathways. METHODS: Apoptosis in the transformed rat RGC-5 was induced by serum deprivation for 0, 8, 24, 48, and 96 h. Briefly, 400 ng of RNA from each sample was reverse transcribed and labeled with Cy3 dye. Fragmented fluorescent cRNA was mixed with hybridization buffer and incubated at 60 degrees C for 16 h. Labeled cRNA was hybridized to Rat Genome Oligonucleotide Arrays. These arrays contain 22,775 transcripts with one oligonucleotide per transcript (60-mer). Gene expression from scanned images was quantified and analyzed using ArrayVision software. Reproducibility among triplicate arrays was determined by ANOVA statistical analysis. Significant differences in gene expression between apoptotic and nonapoptotic cells were determined based on p-values. RESULTS: Of the 22,775 transcripts present on the arrays (Agilent rat genome, 60-mer), 713 (8 h), 1,967 (24 h), 1,011 (48 h), and 1,161 (96 h) were differentially expressed relative to the 0 h time point (p-values <0.05). Twenty-three transcripts were common to 8, 24, 48, and 96 h and 130 transcripts were common to the 24, 48, and 96 h time points. The two most highly upregulated genes were Fdft1 and Lgals3 (8 h), C3 and Fcgrt (24 h), C and Lcn2 (48 h), and Mgp and C3 (96 h). A subset of the differentially expressed genes identified in microarray data (Ftl1, C3, C1s, Neu1, Polr2g, Acadm, Nupr1, Gch, Dia1, DNase1, Tgfb2, and Cyr61) were validated using quantitative real time polymerase chain reaction (QRT-PCR). Here we show that complement factor H (CFH), the major inhibitor of the alternative complement pathway is downregulated in serum-deprived RGC-5. CFH protein was detected within RGC-5 cells as well as the rat retina with the aid of immunocytochemistry and confocal microscopy. CONCLUSIONS: This study was undertaken to generate a genome wide gene expression profile of RGC-5 after serum deprivation, and to identify candidate and novel genes that may be involved in the signal transduction pathways leading to apoptosis. RGC-5 serum deprivation revealed up-and downregulation in gene expression profiles. The data gathered from this study was the first report that the genes identified in microarray data and validated by real-time RT-PCR may play an important role in RGC-5 cell death. Among the validated genes, C3 and C1s showed significant upregulation of the complement component pathway. The results further indicate that components of the complement pathway are present in neurons of the rat retina. The data indicated that complement factors are likely involved in the pathway leading to ganglion cell death in the serum-deprivation paradigm, which may be similar to the mechanism of cell death in glaucoma. PMID- 17356519 TI - Is lipoprotein(a) a clinically meaningful risk marker for cardiovascular events in healthy women? PMID- 17356520 TI - Is rimonabant a safe and effective treatment for obesity? PMID- 17356521 TI - Hazards of PPI overuse and possible ways to curtail it. PMID- 17356522 TI - Optimizing automated peritoneal dialysis: increasing nightly dialysate flow vs adding a manual daytime exchange. PMID- 17356523 TI - Birth size, adult body composition and muscle strength in later life. AB - OBJECTIVE: Low birth weight has been linked to lower lean body mass and abdominal obesity later in life, whereas high birth weight has been suggested to predict later obesity as indicated by high body mass index (BMI). We examined how birth weight was related to adult body size, body composition and grip strength. DESIGN/SUBJECTS: Cross-sectional study on 928 men and 1075 women born in 1934 1944, with measurements at birth recorded. MEASUREMENTS: Height, weight, waist and hip circumference and isometric grip strength were measured. Lean and fat body mass were estimated by bioelectrical impedance with an eight-polar tactile electrode system. RESULTS: A 1 kg increase in birth weight corresponded in men to a 4.1 kg (95% CI: 3.1, 5.1) and in women to a 2.9 kg (2.1, 3.6) increase in adult lean mass. This association remained significant after adjustment for age, adult body size, physical activity, smoking status, social class and maternal size. Grip strength was positively related to birth weight through its association with lean mass. The positive association of birth weight with adult BMI was explained by its association with lean mass. Low birth weight was related to higher body fat percentage only after adjustment for adult BMI. Abdominal obesity was not predicted by low birth weight. CONCLUSIONS: Low birth weight is associated with lower lean mass in adult life and thus contributes to the risk of relative sarcopenia and the related functional inability at the other end of the lifespan. At a given level of adult BMI, low birth weight predicts higher body fat percentage. PMID- 17356524 TI - The biological predisposition to obesity: beyond the thrifty genotype scenario. PMID- 17356525 TI - The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals. AB - BACKGROUND: Previous studies have suggested that a variant in the melanocortin-4 receptor (MC4R) gene is important in protecting against common obesity. Larger studies are needed, however, to confirm this relation. METHODS: We assessed the association between the V103I polymorphism in the MC4R gene and obesity in three UK population based cohort studies, totalling 8304 individuals. We also did a meta-analysis of relevant studies, involving 10 975 cases and 18 588 controls, to place our findings in context. FINDING: In an analysis of all studies, individuals carrying the isoleucine allele had an 18% (95% confidence interval 4 30%, P=0.015) lower risk of obesity compared with non-carriers. There was no heterogeneity among studies and no apparent publication bias. INTERPRETATION: This study confirms that the V103I polymorphism protects against human obesity at a population level. As such it provides proof of principle that specific gene variants may, at least in part, explain susceptibility and resistance to common forms of human obesity. A better understanding of the mechanisms underlying this association will help determine whether changes in MC4R activity have therapeutic potential. PMID- 17356526 TI - How adaptations of substrate utilization regulate body composition. AB - OBJECTIVE: To elucidate the mathematical relationship between longitudinal changes of body composition and the adaptations of substrate utilization required to produce those changes. DESIGN: We developed a simple mathematical model of macronutrient balance. By using an empirical relationship describing lean body mass as a function of fat mass, we derived a mathematical expression for how substrate utilization adapts to changes of diet, energy expenditure and body fat such that energy imbalances produced the required changes of body composition. RESULTS: The general properties of our model implied that short-term changes of dietary fat alone had little impact on either fat or non-fat oxidation rates, in agreement with indirect calorimetry data. In contrast, changes of non-fat intake caused robust adaptations of both fat and non-fat oxidation rates. Without fitting any model parameters, the predicted body composition changes and oxidation rates agreed with experimental studies of overfeeding and underfeeding when the measured food intake, energy expenditure and initial body composition were used as model inputs. CONCLUSION: This is the first report to define the quantitative connection between longitudinal changes of body composition and the required relationship between substrate utilization, diet, energy expenditure and body fat mass. The mathematical model predictions are in good agreement with experimental data and provide the basis for future study of how changes of substrate utilization impact body composition regulation. PMID- 17356527 TI - The effect of scheduled forced wheel activity on body weight in male F344 rats undergoing chronic circadian desynchronization. AB - OBJECTIVE: To examine whether scheduled forced wheel activity counteracts the increased body weight gain in rats undergoing chronic circadian desynchronization induced by repeated 12-h shifts in the light-dark cycle. DESIGN: Four age- and body weight-matched groups of adult male F344 rats were subjected to 12-h intermittent forced wheel activity daily (2.2 km/day). Each group had the following schedule for 13 weeks: a fixed schedule of a daily 12:12-h light-dark cycle and activity training (WF); a fixed light-dark cycle and 12-h shifts twice a week in activity training (WS); 12-h shifts twice a week in the light-dark cycle and a fixed schedule of activity training (LSWF); and 12-h shifts twice a week in both the light-dark cycle and activity training (LSWS). Two additional age- and body weight-matched sedentary rat groups were selected from our database: one was maintained on a fixed light-dark cycle (LC) and the other was subjected to 12-h shifts twice a week in the light-dark cycle (LS). RESULTS: The four rat groups that were exercised showed different response patterns of the daily body temperature rhythm to different combinations of forced activity and lighting schedules. Their food intake was more than that of the two sedentary rat groups, but their body weight was comparable with that of the LC rats and less than that of the LS rats during the forced activity period. The LSWS rats were heavier than the WF and WS rats in the first and second months of the experimental treatment, but their body weight was comparable with that of the WS and WF rats in the third month. CONCLUSION: Forced activity was effective in reducing the body weight gain in chronic circadian desynchronization that was induced by repeated shifts in the light-dark cycle, although such an effect might become significant only after some time. PMID- 17356528 TI - Impact of weight loss on the metabolic syndrome. AB - OBJECTIVE: To evaluate the effects of weight loss on the risk of having metabolic syndrome after 1 year of treatment with lifestyle modification alone, pharmacotherapy alone (sibutramine) or the combination of the two. DESIGN: Randomized, controlled, 1-year clinical trial. PATIENTS: One hundred and eighty women and 44 men, 18-65 years of age, with a body mass index of 30-45 kg/m(2), free of uncontrolled hypertension or type 1 or 2 diabetes. INTERVENTION: Fifteen milligrams of sibutramine per day alone, lifestyle modification counseling alone, sibutramine plus lifestyle modification counseling or sibutramine plus brief lifestyle modification counseling. MEASUREMENTS: The metabolic syndrome, as defined by the Adult Treatment Panel III. RESULTS: Before treatment, 34.8% of the participants had the metabolic syndrome. Metabolic syndrome was more prevalent in Caucasians than African Americans (42.5 vs 20.3%; P<0.03), in males than females (65.1 vs 34.9%; P<0.002) and in older (>44 years) than younger (or=34) and women (BMI>or=38) who completed 10 years of the study. MEASUREMENTS: HRQL was assessed before treatment and after 0.5, 1, 2, 3, 4, 6, 8 and 10 years. RESULTS: HRQL change during the 10-year observation period largely followed phases of weight loss, weight regain and weight stability. Improvements and deteriorations in HRQL were associated with the magnitude of weight loss or regain, except regarding anxiety. Peak improvements in the surgical group were observed during the first year of weight loss, whereas the weight regain phase (mainly between 1- and 6-year follow-up) was accompanied by a gradual decline in HRQL. The period from 6- to 10-year follow-up was characterized by relatively stable observations in both weight and HRQL. At 10 years, net gains were noted in all HRQL domains compared to baseline. Comparisons of treatment effects on HRQL in the surgical vs conventional group after 10 years showed significantly better outcome in the surgical group on current health perceptions, social interaction, psychosocial functioning and depression, whereas no significant differences were found for overall mood and anxiety. Long-term results of the study suggest that a maintained weight loss of about 10% is sufficient for positive long-term effects on HRQL, a limit that was reached in about two-thirds of the surgically treated patients who completed 10 years of the study. CONCLUSION: Long-lasting weight reduction in the severely obese has a general long-standing positive outcome on HRQL. Bariatric surgery is a favorable option for the treatment of severe obesity, resulting in long-term weight loss and HRQL improvements in a majority of patients. However, difficulties among some surgical patients to control and maintain weight loss over time should not be ignored. Future research should study if the long-term efficacy of bariatric surgery may be further enhanced by implementing lifestyle modification techniques in the postoperative management of patients. PMID- 17356531 TI - Prevention of weight gain in young adults through a seminar-based intervention program. AB - OBJECTIVE: Prevention would be the ideal public health strategy to face the current obesity epidemic. Adoption of healthy lifestyles during the first years of college or university could prevent the onset of weight gain associated with this period of acquired independence and eventually decrease the incidence of obesity. DESIGN: Randomized-controlled trial over a period of 2 years. The subjects received an educational/behavioral intervention (small group seminars) designed to help maintain a healthy lifestyle or no specific intervention (control group). SUBJECTS: One-hundred and fifteen non-obese freshmen in a Faculty of Medicine. MEASUREMENTS: Anthropometric measurements, physical activity level, fitness level, food intake and lipid profile were recorded at predetermined intervals. RESULTS: The control group gained weight, whereas the intervention group lost a slight amount of weight over 2 years. The difference between the two groups was 1.3 kg at the end of the follow-up, the trend of weight gain differing between the two groups during the 2-year intervention period (P=0.04). There was no detectable difference in fitness, physical activity level or total caloric intake between the two groups during follow-up. However, plasma triglyceride levels increased in the control group and decreased in the intervention group (P=0.04). CONCLUSION: In this randomized-controlled trial, a small-group seminar educational/behavioral intervention successfully prevents weight gain in normal weight young healthy university students. Such small absolute changes in body composition and lipid profile, if maintained over a prolonged period, could result in significant long-term health benefits for the general population. PMID- 17356532 TI - Diagnostic testing in episodic migraine: should it include magnetic resonance venography? PMID- 17356533 TI - Does palliative chemotherapy beyond three courses benefit patients with non-small cell lung cancer? PMID- 17356534 TI - Is preoperative chemotherapy useful for nonmetastatic Wilms' tumor? PMID- 17356535 TI - Long-term effects of early treatment in patients with rheumatoid arthritis. PMID- 17356536 TI - Different physiotherapy regimens for back and neck pain. PMID- 17356537 TI - What has 20 years' experience of ileal orthotopic bladder substitution taught us? PMID- 17356538 TI - Mid-urethral slings: surgical evolution as manifest by technology. PMID- 17356539 TI - Effects of MIP-1 alpha, MIP-3 alpha, and MIP-3 beta on the induction of HIV Gag specific immune response with DNA vaccines. AB - Transfection of DNA vaccines with chemokines may recruit dendritic cells (DCs) locally to capture the antigenic genes and their gene products to generate enhanced CD8(+) cytotoxic T lymphocytes (CTLs). In this study, we investigated the effects of macrophage inflammatory protein (MIP)-1 alpha, MIP-3 alpha, and MIP-3beta on human immunodeficiency virus (HIV) Gag DNA vaccination. The chemokine plasmids markedly enhanced the local infiltration of inflammatory cells and increased the presence of CD11c(+) B7.2(+)-activated DCs. MIP-1 alpha and MIP 3 alpha were potent adjuvants in augmenting CTLs and afforded strong protection to immunized animals against challenge with vaccinia virus expressing Gag (vv Gag). However, decreased humoral response was observed. MIP-3beta plasmid did not dramatically alter immunity. The chemokine inoculation time with respect to DNA vaccine priming was also investigated. The injection of pMIP-3 alpha three days before Gag plasmid (pGag) vaccination markedly increased specific CTLs compared with simultaneous injection and led to higher protection against vv-Gag. Immunity was also shifted toward a T-helper type-1 (Th1) response. In contrast, inoculation with pMIP-3 alpha three days after pGag vaccination shifted immunity toward a Th2 response. Our data suggest that administration of a chemokine with DNA vaccines offers a valuable strategy to modulate the efficacy and polarization of specific immunity and that chemokine-antigen timing is critical in determining overall biological effects. PMID- 17356540 TI - Human embryonic stem cells and gene therapy. AB - Human embryonic stem cells (hESCs) theoretically represent an unlimited supply of normal differentiated cells to engineer diseased tissues to regain normal function. However, before hESCs can be useful as human therapeutics, technologies must be developed to provide them with the specific signals required to differentiate in a controlled fashion, to regulate and/or shut down the growth of hESCs and their progeny once they have been transferred to the recipient, and to circumvent the recognition of non-autologous hESC-derived cells as foreign. In the context that gene therapy technologies represent strategies to deliver biological signals to address all of these challenges, this review sets out a framework for combined gene transfer/hESC therapies. We discuss how hESCs are derived, characterized, and differentiated into specific cell lineages, and we summarize the characteristics of the 500 hESC lines reported to date. The successes and failures of gene transfer to hESCs are reviewed for both non-viral and viral vectors, as are the challenges to successful use of gene transfer in developing hESC therapy. We also consider gene transfer as a means of facilitating growth and isolation of genetically modified hESCs and as a mechanism for mitigating adverse effects associated with administration of hESCs or their derivatives. Finally, we evaluate the challenges that are likely to be encountered in translating the promise of hESCs to the clinic. PMID- 17356541 TI - Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virus. AB - Drug toxicity and viral resistance limit the long-term efficacy of antiviral drug treatment for human immunodeficiency virus (HIV) infection. Thus, alternative therapies need to be explored. We tested the infusion of T lymphocytes transduced with a retroviral vector (M87o) that expresses an HIV entry-inhibitory peptide (maC46). Gene-modified autologous T cells were infused into ten HIV-infected patients with advanced disease and multidrug-resistant virus during anti retroviral combination therapy. T-cell infusions were tolerated well, with no severe side effects. A significant increase of CD4 counts was observed after infusion. At the end of the 1-year follow-up, the CD4 counts of all patients were still around or above baseline. Gene-modified cells could be detected in peripheral blood, lymph nodes, and bone marrow throughout the 1-year follow-up, and marking levels correlated with the cell dose. No significant changes of viral load were observed during the first 4 months. Four of the seven patients who changed their antiviral drug regimen thereafter responded with a significant decline in plasma viral load. In conclusion, the transfer of gene-modified cells was safe, led to sustained levels of gene marking, and may improve immune competence in HIV-infected patients with advanced disease and multidrug-resistant virus. PMID- 17356542 TI - DNA vaccines encoding Ii-PADRE generates potent PADRE-specific CD4+ T-cell immune responses and enhances vaccine potency. AB - It is now clear that CD4+ T cells play a crucial role in the generation of CD8+ T effector and memory T-cell immune responses. In this study, we enhanced the CD4+ T-cell immune responses in mice by constructing a DNA vaccine encoding an invariant (Ii) chain in which the class II-associated Ii peptide (CLIP) region is replaced with a CD4+ T-helper epitope, PADRE (Ii-PADRE) (invariant Pan HLA-DR reactive epitope). C57BL/6 mice vaccinated with DNA encoding Ii-PADRE showed significantly greater PADRE-specific CD4+ T-cell immune responses than mice vaccinated with DNA encoding the Ii chain alone (Ii DNA). More important, administration of DNA encoding human papillomavirus (HPV) E6 or E7 antigen with DNA encoding Ii-PADRE led to significantly stronger E6- or E7-specific CD8+ T cell immune responses and more potent protective and therapeutic anti-tumor effects against an E6/E7-expressing tumor model in mice than administration of E6 or E7 DNA with Ii DNA. Overall, our data indicate that administration of DNA vaccines with Ii-PADRE DNA represents an effective approach to enhancing the generation of CD4+ T cells and eliciting stronger antigen-specific CD8+ T-cell immune responses. Therefore, this strategy may be expected to have significant potential for clinical translation. PMID- 17356543 TI - Imaging the modulation of adenoviral kinetics and biodistribution for cancer gene therapy. AB - To explore systemic utilization of Epstein-Barr virus (EBV)-specific transcriptionally targeted adenoviruses, three vectors were constructed to examine kinetics, specificity, and biodistribution: adv.oriP.luc, expressing luciferase under EBV-specific control; adv.SV40luc, expressing luciferase constitutively; and adv.oriP.E1A.oriP.luc, a conditionally replicating adenovirus, expressing both luciferase and E1A. Bioluminescence imaging (BLI) was conducted on tumor-bearing severe combined immunodeficient (SCID) mice (C666-1, EBV-positive human nasopharyngeal cancer) treated intravenously (i.v.) with 3 x 10(8) infectious units (ifu) of the adenoviral vectors. At 72 hours, adv.oriPluc demonstrated an 8.4-fold higher tumor signal than adv.SV40luc; adv.oriP.E1A.oriP.luc was 26.7-fold higher; however, a significant liver signal was also observed, necessitating further action to improve biodistribution. Several compounds were examined to this end, including norepinephrine, serotonin, clodronate liposomes, and STI571, to determine whether any of these measures could improve adenoviral biodistribution. Each of these interventions was assessed using BLI in mice i.v. injected with adv.oriP.luc. STI571 achieved the highest increase in tumor-to-liver ratio (TLR; 6.6-fold), which was associated with a 59% reduction in tumor interstitial fluid pressure (IFP) along with a decrease in platelet-derived growth factor-beta receptor (PDGF beta R) activation. This study reports the favorable modulation by STI571 of the biodistribution of adenoviral vectors, providing a potential approach to improving therapeutic outcome. PMID- 17356544 TI - Loss of transgene following ex vivo gene transfer is associated with a dominant Th2 response: implications for cutaneous gene therapy. AB - Host responses to therapeutic gene products are potentially serious complications in cutaneous gene therapy. Controlling immune responses to the therapeutic antigen may therefore be critical for an effective therapy. Both ex vivo and in vivo gene transfer to epidermal stem cells has been shown to induce transgene specific immune responses; however, whether the mechanism of immune activation is the same is not clear. In this study, we have characterized transgene-specific immune responses in an ex vivo model of epidermal gene transfer using green fluorescent protein as a model antigen and retrovirus-mediated gene delivery. Contrary to T helper (Th)1-type responses induced following in vivo gene transfer to epidermis, rejection of ex vivo-transduced keratinocytes was associated with Th2/eosinophilc responses. These responses were characterized by interleukin (IL) 4 and IL-5 production by T cells, a predominance of anti-green fluorescent protein IgG1 in serum, the presence of numerous eosinophils within rejected skin, and a lack of class I-restricted cytotoxic T lymphocyte response. Pretreatment of mice receiving ex vivo transduced keratinocytes with neutralizing anti-IL-5 antibody prevented eosinophil infiltration and prolonged survival of transduced epidermis. These data indicate a role for the Th2/eosinophilic pathway in rejection of ex vivo-transduced keratinocytes, suggesting different requirements for achieving tolerance for ex vivo and in vivo approaches to gene therapy. PMID- 17356545 TI - A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia. AB - We describe the clinical and biochemical characteristics in three patients from two different families diagnosed with Congenital Disorder of Glycosylation type IIe owing to a defect in Conserved Oligomeric Golgi complex (COG)7; one of the eight subunits of the COG. The siblings and an unrelated single child of consanguineous parents presented with growth retardation, progressive, severe microcephaly, hypotonia, adducted thumbs, feeding problems by gastrointestinal pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin and episodes of extreme hyperthermia. A combined disorder in the biosynthesis of N- and O-linked glycosylation with hyposialylation was detected. Western blot analysis showed a severe reduction in the COG5 and 7 subunits of the COG. A homozygous, intronic splice site mutation (c.169+4A>C) of the COG7 gene was identified in all patients. The phenotype is similar to that previously described in two patients of North African ethnicity with the same mutation, except for the lack of skeletal anomalies and only a mild liver involvement in our patients. We suggest performing protein glycosylation studies and Western blot for the different COG subunits in patients with progressive microcephaly, growth retardation, hypotonia, adducted thumbs and cardiac defects, especially in association with skin anomalies or episodes of hyperthermia. The presence of the characteristic phenotype might warrant direct DNA analysis. PMID- 17356546 TI - Does apolipoprotein E determine outcome of infection by varicella zoster virus and by Epstein Barr virus? AB - Over 90% of the population are infected with varicella zoster virus (VZV) but only some develop shingles - caused when the virus reactivates from latency, and only some shingles patients develop post-herpetic neuralgia (PHN), defined as pain continuing for more than about 4 months. Epstein Barr virus (EBV) similarly infects over 90% of the population; some of those infected during teenage or young adult years develop infectious mononucleosis (IM). The reason for these disparities between numbers infected and numbers affected by illness is unknown, but presumably reflects host factor(s). Our previous results showed that apolipoprotein E (APOE) genotype determines susceptibility to, or outcome of, infection in the case of several diseases of known infectious cause. Therefore, we investigated APOE genotypes of shingles, PHN, and IM patients. Our rationale for the previous studies and for investigating VZV was that these micro-organisms use for cell binding and entry the same sites in the cell surface as does the protein apoE, and that consequently, competition with apoE could affect the pathogen's extent of entry and hence extent of the damage caused. The APOE genotypes of shingles and PHN sufferers, and of IM sufferers were determined using restriction fragment length polymorphism. In females, epsilon4 homozygosity confers a risk of shingles and also of IM, and the APOE-epsilon4 allele is protective against PHN whereas APOE-epsilon3 allele is a risk. Our results showing that a host genetic factor influences the development of shingles and PHN in females have clinical significance: they could lead to identification of those (female) patients at greater risk of PHN, thus enabling these people to be targeted for treatment with the most effective drugs. PMID- 17356547 TI - Insights into modern disease from our distant evolutionary past. AB - An EMBO workshop entitled 'Human Evolution and Disease' was held recently (6-9 December 2006, Hyderabad, India) where 141 scientists from many disciplines came together to discuss recent studies of human variation, origins and dispersal, natural selection and disease susceptibility. The meeting tackled the subject of human evolution and disease from the different perspectives of archaeology, linguistics, genetics and genomics based on both new and publicly available data sets. In this report, we highlight the latest fashion crazes in the discipline, in particular, the use of large public data sets and new methods to analyse modern human variation and the links between human evolution and disease susceptibility. PMID- 17356548 TI - A legal framework for biobanking: the German experience. AB - Although biobanks are vital for modern medical research, serious concerns have been raised about the legal basis and framework of such endeavours. This led the German 'Telematics Platform for Medical Research Networks' ('Telematikplattform fur Medizinische Forschungsnetze', TMF) to initiate a project in 2004 that was designed to place German biobanks on a sound legal footing. This project involved the planning, writing and evaluation of an expert report that addresses in great detail the legal issues concerning property rights, medical professional regulations, general liability insurance, resource continuity and research secrecy. Here, we provide a brief summary of the major results of this project. PMID- 17356549 TI - Cytogenetic Guidelines and Quality Assurance: a common European framework for quality assessment for constitutional and acquired cytogenetic investigations. PMID- 17356550 TI - Phenotype selection for detecting variable genes: a survey of cardiovascular quantitative traits and TNF locus polymorphism. AB - The practice of using discrete clinical diagnoses in genetic association studies has seldom led to a replicable genetic model. If, as the literature suggests, weak genotype-phenotype relationships are detected when clinical diagnoses are used, power might be increased by exploring more fundamental biological traits. Emerging solutions to this include directly modeling levels of the protein product of a gene (usually in plasma) and sequence variation specifically in/around that gene, as well as exploring multiple quantitative traits related to a disease of interest. Here, we attempt a strategy based upon these premises examining sequence variants near the TNF locus, a region widely studied in cardiovascular disease. Multilocus genotype models were used to perform a systematic screen of 18 metabolic and anthropometric traits for genetic association. While there was no evidence for an effect of TNF polymorphism on plasma TNF levels, a relatively strong effect on plasma PAI-1 levels did emerge (P=0.000019), but this was only evident in post-myocardial infarction patients. Modeled jointly with the common 4G/5G insertion/deletion polymorphism of SERPINE1 (formerly PAI), this effect appears large (10% of variance explained versus 2% for SERPINE1 4G/5G). We exhibit this finding cautiously, and use it to illustrate how transitioning the study of disease risk to quantitative traits might empower the identification of functionally variable genes. Further, a case is highlighted where association between sequence variation in a gene and its product is not readily apparent even in large samples, but where association with a down-stream pathway may be. PMID- 17356553 TI - Consumption of 'extra' foods by Australian children: types, quantities and contribution to energy and nutrient intakes. AB - OBJECTIVE: To measure the types and quantities of energy-dense, nutrient-poor 'extra' foods consumed by Australian children and adolescents and their contribution to total energy and nutrient intakes. DESIGN, SETTING AND SUBJECTS: We used data from 3007 children, aged 2-18 years, who participated in the nationally representative 1995 National Nutrition Survey. Intake was determined by 24-h recall and 'extra' foods were defined using principles outlined in the Australian Guide to Healthy Eating (AGHE) and by applying cut points for maximum amounts of fat and sugar within each food category. RESULTS: All children (99.8%) consumed at least one 'extra' food and the most commonly consumed were margarine, sugar-sweetened soft drinks, cordials and sugar. 'Extra' foods contributed 41% of daily energy intake. Those foods contributing most to energy intake were fried potatoes (4.2%), sugar-sweetened soft drinks (3.3%), ice cream/ice confection (3.1%) and cordials (2.7%). Age and sex were important determinants of 'extra' food intake, with males and older children generally consuming more and different types of, 'extra' foods than females and younger children. 'Extra' foods contributed 19% protein, 47% total fat, 47% saturated fat, 54% sugar, and approximately 20-25% of selected micronutrients to the diet. Calcium and zinc intakes from core foods were below 70% of the recommended dietary intakes for adolescent girls. CONCLUSIONS: 'Extra' foods are over-consumed at two to four times the recommended limits and contribute excessively to the energy, fat and sugar intakes of Australian children, while providing relatively few micronutrients. This is of concern in terms of children's weight and nutrient status. PMID- 17356554 TI - Probiotic capsules do not lower plasma lipids in young women and men. AB - OBJECTIVE: To investigate the effect of probiotic capsules on plasma lipids. DESIGN: A randomized, single-blinded, placebo-controlled, parallel-arm trial. SUBJECTS: Fifty-five normocholesterolemic subjects ages 18-36 (33 premenopausal women and 22 men). INTERVENTION: Each subject consumed either three probiotic capsules each containing a total of 10(9) colony-forming units Lactobacillus acidophilus and Bifidobacterium longum and 10-15 mg fructo-oligosaccharide or three placebo capsules daily for 2 months (men) or two menstrual cycles (women). Plasma lipids were measured before and following the intervention (during the early follicular phase for women). RESULTS: Plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride were not altered by consumption of probiotic or placebo capsules and were not different between treatment groups following the intervention. CONCLUSIONS: These results do not support a beneficial effect of Lactobacillus acidophilus strain DDS-1 and Bifidobacterium longum strain UABL-14 on plasma lipids in normocholesterolemic young women and men. SPONSORSHIP: Supported by the Minnesota Agricultural Experiment Station and UAS Laboratories. PMID- 17356555 TI - Prevention of antibiotic-associated diarrhoea by a fermented probiotic milk drink. AB - OBJECTIVE: To study the preventive effect of a milk drink fermented with multistrain probiotics on antibiotic associated diarrhoea (AAD). DESIGN: Double blind placebo controlled study. SETTING: University Hospital of North Norway. SUBJECTS AND METHODS: Of 853 patients treated with antibiotics, 87 met the inclusion criteria, and were randomized to ingestion of a fermented milk drink containing LGG, La-5 and Bb-12 (n=46) or placebo with heat-killed bacteria (n=41), during a period of 14 days. A diary was recorded, and stool samples were collected for microbiological analyses. RESULTS: Sixty-three patients completed the study according to the protocol; two patients (5.9%) in the treatment group and eight (27.6%) in the placebo group developed AAD (P=0.035). The relative risk of developing AAD was 0.21 (95% confidence interval: 0.05-0.93) when given probiotic milk drink. CONCLUSION: A fermented multistrain probiotic milk drink may prevent four of five cases of AAD in adult hospitalized patients. SPONSORSHIP: TINE BA, Oslo, Norway. PMID- 17356556 TI - The metabolic fate of doubly stable isotope labelled heat-killed Lactobacillus johnsonii in humans. AB - OBJECTIVE: In this study, heat-killed Lactobacillus johnsonii (La1), doubly labelled with (13)C and (15)N (hk-dlLa1), was used to follow the metabolic fate after oral administration in humans. DESIGN: Experimental study. SETTING: University of Rostock, Children's Hospital, Research Laboratory. SUBJECTS: Ten healthy adults aged 23-26 years. INTERVENTION: The subjects received 74.6 mg/kg body weight hk-dlLa1 and 10 g alpha-D-raffinose together with breakfast. A sample of venous blood was taken after 2 h. Expired air samples were taken over 14 h, whereas urine and faeces were collected over a period of 48 h. (13)C- and (15)N enrichments were measured by isotope ratio mass spectrometry. Hydrogen concentrations were measured by electrochemical detection. RESULTS: The orocaecal transit time (OCTT) was reached after 3.4 h. After 2 h, (13)C- and (15)N enrichment of fibrinogen amounted to 2 and 25 p.p.m. excess, respectively. The (13)CO(2)-exhalation amounted to 9.2% of the ingested dose. The urinary excretion of (13)C and (15)N was 2.1 and 10.4% of the ingested dose, respectively, whereas the faecal excretion was 47.9 and 43.7% of the ingested dose, respectively. CONCLUSIONS: In comparison to OCTT of 3.4 h, both stable isotopes appear after 30 min in breath and urine, indicating that hk-dlLa1 is rapidly digested in the small bowel before reaching the caecum. This is confirmed by (13)C-and (15)N enrichments of blood plasma fractions. The ingestion of hk-dlLa1 led to a (13)C- and (15)N-excretion of 59.2 and 54.1% of the ingested dose, respectively, of both stable isotopes. PMID- 17356557 TI - Development of bioelectrical impedance-derived indices of fat and fat-free mass for assessment of nutritional status in childhood. AB - OBJECTIVES: (1) To develop a method of manipulating bioelectrical impedance (BIA) that gives indices of lean and fat adjusted for body size, using a large normative cohort of children. (2) To assess the discriminant validity of the method in a group of children likely to have abnormal body composition. DESIGN: Two prospective cohort studies. SETTING: Normative data: Avon Longitudinal Study of Parents and Children (ALSPAC), population based cohort; proof of concept study: tertiary feeding clinic and special needs schools. SUBJECTS: Normative data: 7576 children measured aged between 7.25 and 8.25 (mean 7.5) (s.d.=0.2) years; proof of concept study: 29 children with either major neurodisability or receiving artificial feeding, or both, mean age 7.6 (s.d.=2) years. MEASURES: Leg to-leg (Z (T)) and arm-to-leg (Z (B)) BIA, weight and height. Total body water (TBW) was estimated from the resistance index (RI=height(2)/Z), and fat-free mass was linearly related to TBW. Fat mass was obtained by subtracting fat-free mass from total weight. Fat-free mass was log-transformed and the reciprocal transform was taken for fat mass to satisfy parametric model assumptions. Lean and fat mass were then adjusted for height and age using multiple linear regression models. The resulting standardized residuals gave the lean index and fat index, respectively. RESULTS: In the normative cohort, the lean index was higher and fat index lower in boys. The lean index rose steeply to the middle of the normal range of body mass index (BMI) and then slowly for higher BMI values, whereas the fat index rose linearly through and above the normal range. In the proof of concept study, the children as a group had low lean indices (mean (s.d.) -1.5 (1.7)) with average fat indices (+0.21 (2.0)) despite relatively low BMI standard deviation scores (-0.60 (2.3)), but for any given BMI, individual children had extremely wide ranges of fat indices. The lean index proved more stable and repeatable than BMI. CONCLUSIONS: This clinical method of handling BIA reveals important variations in nutritional status that would not be detected using anthropometry alone. BIA used in this way would allow more accurate assessment of energy sufficiency in children with neurodisability and may provide a more valid identification of children at risk of underweight or obesity in field and clinical settings. PMID- 17356558 TI - Relationship between meat intake and the development of acute coronary syndromes: the CARDIO2000 case-control study. AB - OBJECTIVE: The aim of the present study was to evaluate the association between meat consumption and the prevalence of a first, non-fatal event of an acute coronary syndrome (ACS), in a Greek sample. DESIGN: Randomized, case-control study. SETTING: Tertiary care. SUBJECTS: A total of 848 out of 956 patients who had been randomly selected from hospitals with first event of an ACS and 1078 population-based controls, age and sex matched. INTERVENTIONS: Detailed information regarding their medical records, alcohol intake, physical activity and smoking habits was recorded. Nutritional habits were evaluated with a semiquantitative food-frequency questionnaire. Multiple logistic regression analysis estimated the odds ratio of having ACS by level of meat intake, after taking into account several confounders. RESULTS: Patients consumed higher quantities of meat compared with controls (6.5+/-2.9 vs 4.9+/-2.1 portions per month, P<0.001). Food-specific analysis showed that red meat consumption was strongly associated with 52% increased odds of ACS (95% confidence interval (CI) 1.47-1.58). On the contrary, white meat consumption seems to be associated with only 18% likelihood of having cardiac events (95% CI 1.11-1.26). Participants who consumed >8 portions red meat and >12 portions white meat per month had 4.9 times and 3.7 higher odds of having ACS, respectively (P<0.001), compared with low meat intake (<4 portions and <8 portions per month, respectively). CONCLUSIONS: Increased red meat consumption showed a strong positive association with cardiac disease risk, whereas white meat consumption showed less prominent results, after controlling for several potential confounding factors. PMID- 17356559 TI - Carotid artery compliance in users of plant stanol ester margarine. AB - OBJECTIVE: To investigate the effects of stanol ester margarine use in healthy subjects on arterial compliance, endothelial function and intima-media thickness. DESIGN: Case-control study comparing regular stanol ester margarine users to non users. SETTING: Occupational health service clinic. SUBJECTS: We recruited 50 cases and 50 controls (mean age 51+/-8, range 26-65 years). All subjects were non smokers and the study groups were matched for age and sex. As cases, we invited subjects who had been using regularly (daily) plant stanol ester margarine for a period of 2 years or longer. Non-invasive ultrasound was used to measure carotid artery compliance, carotid intima-media thickness and brachial artery flow mediated endothelial dependent vasodilatation. RESULTS: The carotid artery compliance was non-significantly higher in cases compared with controls, 1.84+/ 1.02 vs 1.58+/-0.76 %/10 mm Hg (P=0.13). The difference in compliance became statistically significant (P=0.04) when the unbalance between the groups in family history of coronary artery disease and years of education were taken into account. There was also a significant dose-response relationship between stanol margarine use and carotid compliance, longer use being associated with higher compliance. Serum lipoproteins, blood pressure, flow-mediated dilation and intima media thickness values did not differ between cases and controls. CONCLUSION: These data raise the possibility that regular stanol ester margarine use may be associated with beneficial changes in arterial compliance. Intervention studies are needed to test this hypothesis and to reveal possible mechanisms. PMID- 17356560 TI - Associations between estimated acrylamide intakes, and hemoglobin AA adducts in a sample from the Malmo Diet and Cancer cohort. AB - OBJECTIVE: To examine the coherence of estimated intakes of acrylamide (AA) from foods, with hemoglobin (Hb) AA adduct levels, an objective marker of environmental AA exposure. DESIGN: A cross-sectional study. SETTING: The Malmo Diet and Cancer study, a large population-based prospective cohort (n=28 098) in the south of Sweden. SUBJECTS: A sample of non-smoking (n=70) and smoking (n=72) women and men selected to obtain large variation in Hb AA adducts. METHODS: Self reported data on the usual consumption of foods were combined with published data on the AA content in Swedish foods. The Hb AA adduct levels were determined by a modified Edman degradation method. Linear regression and correlation analysis examined associations between estimated AA intakes, and Hb AA adducts. RESULTS: In randomly selected individuals (n=40), the estimated median AA intake was 28 mug per day. In linear regression models, adjusting for sex, significant associations were seen in non-smokers between Hb AA adducts and estimated AA from foods (P=0.006). In smokers both AA from foods (P=0.006) and the calculated amount of tobacco consumed (P=0.003) were significantly associated with Hb AA adducts. Positive partial correlations between dietary AA estimates and Hb AA adducts were seen in smoking men (r=0.37) and women (r=0.59), and in non-smoking men (r=0.60), but not in non-smoking women. CONCLUSIONS: This study suggests that both diet and tobacco are important sources of the environmental AA exposure, although the lack of correlations in non-smoking women cast doubt on the validity of dietary AA intake estimates used in cancer epidemiology, or suggest that unrecognized factors may influence the internal dose measure of AA exposure. PMID- 17356561 TI - Total cardiovascular risk profile of Taiwanese vegetarians. AB - BACKGROUND: Although the health benefits of vegetarian diets have been well documented among Western population, there are geographic differences of vegetarian diets and the health benefits of the Taiwanese vegetarian diet have not been studied extensively. In addition to conventional risk factors, homocysteine and high-sensitivity C-reactive protein (hs-CRP) levels have been found to predict first atherothrombotic events. We undertook this study to examine the total risk profile of Taiwanese vegetarians. METHODS: A total of 198 healthy subjects (99 vegetarians and 99 omnivores) were recruited. Fasting blood samples were analyzed for glucose, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), white blood cell count, hs-CRP and homocysteine. RESULTS: There was no significant difference in age, body mass index, blood glucose, white blood cell count, triglyceride and HDL-C between the two groups. The vegetarian group had significantly more females (65.7 vs 46.5%); lower body weight (58.66+/-11.13 vs 62.88+/-12.24 kg); shorter height (159.14+/-7.88 vs 162.53 +/-8.14 cm); lower total cholesterol (184.74+/-33.23 vs 202.01+/-41.05 mg/dl); and lower LDL-C (119.63+/-31.59 vs 135.89+/-39.50 mg/dl). Hs-CRP was significantly lower (0.14+/ 0.23 vs 0.23+/-0.44 mg/dl, P=0.025), whereas homocysteine was significantly higher (10.97+/-6.69 vs 8.44+/-2.50 micromol/l, P=0.001) in vegetarians than omnivores. CONCLUSIONS: Taiwanese vegetarians have lower total cholesterol, LDL-C and hs-CRP levels, and higher homocysteine levels than omnivores. Owing to different predictive value of each risk factor, the Taiwanese vegetarians had a better cardiovascular risk profile than omnivores. Whether the Taiwanese vegetarian diet should be supplemented with vitamin B(12) to lower serum homocysteine level remains to be addressed. PMID- 17356562 TI - Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke. AB - Bone marrow stromal cells (MSCs) increase vascular endothelial growth factor (VEGF) expression and promote angiogenesis after stroke. Angiopoietin-1 (Ang1) and its receptor Tie2 mediate vascular integrity and angiogenesis as does VEGF and its receptors. In this study, we tested whether MSC treatment of stroke increases Ang1/Tie2 expression, and whether Ang1/Tie2 with VEGF/ vascular endothelial growth factor receptor 2 (VEGFR2) (Flk1), in combination, induced by MSCs enhances angiogenesis and vascular integrity. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAo) and treated with or without MSCs. Marrow stromal cell treatment significantly decreased blood-brain barrier (BBB) leakage and increased Ang1, Tie2, and occludin (a tight junction protein) expression in the ischemic border compared with MCAo control. To further test the mechanisms of MSC-induced angiogenesis and vascular stabilization, cocultures of MSCs with mouse brain endothelial cells (MBECs) or astrocytes were performed. Supernatant derived from MSCs cocultured with MBECs significantly increased MBEC expression of Ang1/Tie2 and Flk1 compared with MBEC alone. Marrow stromal cells cocultured with astrocytes also significantly increased astrocyte VEGF and Ang1/Tie2 expression compared with astrocyte culture alone. Conditioned media from MSCs alone, and media from cocultures of MSCs with astrocytes or MBECs, all significantly increased capillary tube-like formation of MBEC compared with control Dulbecco's modified Eagle's medium media. Inhibition of Flk1 and/or Ang1 significantly decreased MSC-induced MBEC tube formation. Knockdown of Tie2 expression in MBECs significantly inhibited MSC-induced tube formation. Our data indicate MSC treatment of stroke promotes angiogenesis and vascular stabilization, which is at least partially mediated by VEGF/Flk1 and Ang1/Tie2. PMID- 17356563 TI - No effect of low-dose statins treatment on cerebral blood flow in humans with atherosclerotic cerebrovascular disease. AB - Animal studies have suggested that the reduction in stroke risk observed with 3 hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) therapy is owing to an increase in basal cerebral blood flow (CBF). The purpose of the study was to determine if statin therapy was associated with increased CBF in humans with cerebrovascular atherosclerotic disease. Quantitative measurements of CBF were obtained on study entry in 97 patients with carotid artery occlusion enrolled in a prospective study of cerebral hemodynamics and stroke risk. This study represents a post hoc analysis of CBF measurements based on whether patients were receiving statin therapy at the time of CBF measurement. Global and regional CBF (including hemispheric, basal ganglia, and arterial borderzones), and baseline clinical, epidemiologic, and laboratory stroke risk factors were compared between the two groups. Nineteen of the 97 patients were on a statin agent on study entry. The statin group was younger, had significantly lower LDL levels and included more women. Statin therapy was not associated with higher baseline values of CBF in global or regional analyses. Mean middle cerebral artery territory CBF (+/-s.d.) ipsilateral to the occluded carotid artery was 37.6+/-12.7 mL/100 g min for the statin group (n=19) compared with 38.6+/-12.7 mL/100 g min for the nonstatin group (n=78). Contralateral values were 42.9+/ 13.5 and 44.2+/-13.3 mL/100 g min for the statin and nonstatin groups, respectively. We conclude that the stroke risk reduction observed with statin therapy in humans likely involves mechanisms other than an increased basal CBF. PMID- 17356564 TI - Human breast biomonitoring and environmental chemicals: use of breast tissues and fluids in breast cancer etiologic research. AB - Extensive research indicates that the etiology of breast cancer is complex and multifactorial and may include environmental risk factors. Breast cancer etiology and exposure to xenobiotic compounds, diet, electromagnetic fields, and lifestyle have been the subject of numerous scientific inquiries, but research has yielded inconsistent results. Biomonitoring has been used to explore associations between breast cancer and levels of environmental chemicals in the breast. Research using breast tissues and fluids to cast light on the etiology of breast cancer is, for the most part, predicated on the assumption that the tissue or fluid samples either contain measurable traces of the environmental agent(s) associated with the cancer or that they retain biological changes that are biomarkers of such exposure or precursors of carcinogenic effect. In this paper, we review breast cancer etiology research utilizing breast biomonitoring. We first provide a brief synopsis of the current state of understanding of associations between exposure to environmental chemicals and breast cancer etiology. We then describe the published breast cancer research on tissues and fluids, which have been used for biomonitoring, specifically human milk and its components, malignant and benign breast tissue, nipple aspirate fluid (NAF) and breast cyst fluid. We conclude with a discussion on recommendations for biomonitoring of breast tissues and fluids in future breast cancer etiology research. Both human milk and NAF fluids, and the cells contained therein, hold promise for future biomonitoring research into breast cancer etiology, but must be conducted with carefully delineated hypotheses and a scientifically supportable epidemiological approach. PMID- 17356567 TI - The antidepressant desipramine requires the ABCB1 (Mdr1)-type p-glycoprotein to upregulate the glucocorticoid receptor in mice. AB - The mechanisms by which antidepressants regulate the hypothalamic-pituitary adrenal (HPA) axis are still unknown. The ABCB1-type multiple drug resistance (MDR) p-glycoprotein (PGP) regulates the HPA axis by limiting the access of glucocorticoids to the brain in mice and humans. Previous work in cell cultures has found that antidepressants enhance glucocorticoid receptor (GR) function in vitro by inhibiting MDR PGP, and therefore by increasing the intracellular concentration of glucocorticoids-but this model has never been tested directly in animals. Here, the tricyclic antidepressant, desipramine (20 mg/kg/day, i.p., for seven days), was administered to abcb1ab MDR PGP knockout mice (congenic on the FVB/N background strain) and to FVB/N controls. The hippocampal mRNA expression of GR, mineralocorticoid receptor (MR), MDR (Mdr1a) PGP, and 11beta hydroxysteroid dehydrogenase type 1 (11beta-HSD1) were measured, together with plasma corticosterone levels. In FVB/N controls, desipramine induced a significant upregulation of GR mRNA in the CA1 region (+31%; p=0.045); in contrast, in abcb1ab (-/-) mice, desipramine induced a significant downregulation of GR mRNA in the CA1 region (-45%; p=0.004). MR mRNA expression was unaltered. Desipramine decreased corticosterone levels in both FVB/N controls and in abcb1ab (-/-) mice, but in abcb1ab (-/-) mice the effects were smaller. Specifically, in FVB/N controls (but not in abcb1ab (-/-) mice), desipramine reduced corticosterone levels not only compared with saline-treated mice but also compared with the 'physiological' levels of untreated mice (-39%; p=0.05). Finally, desipramine reduced Mdr1a mRNA expression across all hippocampus areas ( 9 to -23%), but had no effect on 11beta-HSD1 mRNA expression. These data support the notion that the MDR PGP is one of the molecular targets through which antidepressants regulate the HPA axis. PMID- 17356569 TI - Iptakalim alleviates rotenone-induced degeneration of dopaminergic neurons through inhibiting microglia-mediated neuroinflammation. AB - Inhibition of microglia-mediated neuroinflammation has been regarded as a prospective strategy for treating neurodegenerative disorders, such as Parkinson's disease (PD). In the present study, we demonstrated that systematic administration with iptakalim (IPT), an adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) opener, could alleviate rotenone-induced degeneration of dopaminergic neurons in rat substantia nigra along with the downregulation of microglial activation and mRNA levels of tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase-2 (COX-2). In rat primary cultured microglia, pretreatment with IPT suppressed rotenone-induced microglial activation evidenced by inhibition of microglial amoeboid morphological alteration, declined expression of ED1 (a marker for activated microglia), and decreased production of TNF-alpha and prostaglandin E2 (PGE(2)). These inhibitory effects of IPT could be reversed by selective mitochondrial K(ATP) (mitoK(ATP)) channel blocker 5-hydroxydecanoate (5-HD). Furthermore, pretreatment with IPT prevented rotenone-induced mitochondrial membrane potential loss and p38/c-jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) activation in microglia, which might in turn regulate microglial activation and subsequent production of TNF-alpha and PGE(2). These data strongly suggest that the K(ATP) opener IPT may be a novel and promising neuroprotective drug via inhibiting microglia-mediated neuroinflammation. PMID- 17356568 TI - Neurotensin receptor antagonist administered during cocaine withdrawal decreases locomotor sensitization and conditioned place preference. AB - Chronic use of psychostimulants induces enduringly increased responsiveness to a subsequent psychostimulant injection and sensitivity to drug-associated cues, contributing to drug craving and relapse. Neurotensin (NT), a neuropeptide functionally linked to dopaminergic neurons, was suggested to participate in these phenomena. We and others have reported that SR 48692, an NT receptor antagonist, given in pre- or co-treatments with cocaine or amphetamine, alters some behavioral effects of these drugs in rats. However, its efficacy when applied following repeated cocaine administration remains unknown. We, therefore, evaluated the ability of SR 48692, administered after a cocaine regimen, to interfere with the expression of locomotor sensitization and conditioned place preference (CPP) in rats. We demonstrated that the expression of locomotor sensitization, induced by four cocaine injections (15 mg/kg, i.p.) every other day and a cocaine challenge 1 week later, was attenuated by a subsequent 2-week daily administration of SR 48692 (1 mg/kg, i.p.). Furthermore, the expression of cocaine-induced CPP was suppressed by a 10-day SR 48692 treatment started after the conditioning period (four 15 mg/kg cocaine injections every other day). Taken together, our data show that a chronic SR 48692 treatment given after a cocaine regimen partly reverses the expression of locomotor sensitization and CPP in the rat, suggesting that NT participates in the maintenance of these behaviors. Our results support the hypothesis that targeting neuromodulatory systems, such as the NT systems may offer new strategies in the treatment of drug addiction. PMID- 17356570 TI - Regional brain activity correlates of nicotine dependence. AB - Fifteen smokers participated in a study investigating brain correlates of nicotine dependence. Dependence was reduced by having subjects switch to denicotinized cigarettes for 2 weeks while wearing nicotine skin patches. Positron emission tomography (PET) scans assessed regional cerebral metabolic rate for glucose (rCMRglc) after overnight nicotine abstinence on three occasions: (1) at baseline; (2) after 2 weeks of exposure to denicotinized cigarettes+nicotine patches; and (3) 2 weeks after returning to smoking the usual brands of cigarettes. Craving for cigarettes and scores on the Fagerstrom Test of Nicotine Dependence (FTND) questionnaire decreased at the second session relative to the first and last sessions. Regional brain metabolic activity (normalized to whole brain values) at session 2 also showed a significant decrease in the right hemisphere anterior cingulate cortex. Exploratory post hoc analyses showed that the change in craving across sessions was negatively correlated with the change in rCMRglc in several structures within the brain reward system, including the ventral striatum, orbitofrontal cortex and pons. The between-session difference in thalamus activity (right hemisphere) was positively correlated with the difference in FTND scores. Correlational analyses also revealed that reported smoking for calming effects was associated with a decrease (at session 2) in thalamus activity (bilaterally) and with an increase in amygdala activity (left hemisphere). Reported smoking to enhance pleasurable relaxation was associated with an increase in metabolic activity of the dorsal striatum (caudate, putamen) at session 2. These findings suggest that reversible changes in regional brain metabolic activity occur in conjunction with alterations in nicotine dependence. The results also highlight the likely role of thalamic gating processes as well as striatal reward and corticolimbic regulatory pathways in the maintenance of cigarette addiction. PMID- 17356571 TI - Chronic antidepressants induce redistribution and differential activation of alphaCaM kinase II between presynaptic compartments. AB - Changes in synaptic plasticity are involved in pathophysiology of depression and in the mechanism of antidepressants. Ca(2+)/calmodulin (CaM) kinase II, a protein kinase involved in synaptic plasticity, has been previously shown to be a target of antidepressants. We previously found that antidepressants activate the kinase in hippocampal neuronal cell bodies by increasing phosphorylation at Thr(286), reduce the kinase phosphorylation in synaptic membranes, and in turn its phosphorylation-dependent interaction with syntaxin-1 and the release of glutamate from hippocampal synaptosomes. Here, we investigated the chronic effect of different antidepressants (fluoxetine, desipramine, and reboxetine) on the expression and function of the kinase in distinct subcellular compartments in order to dissect the different kinase pools affected. Acute treatments did not induce any change in the kinase. In total tissue extracts chronic drug treatments induced activation of the kinase; in hippocampus (HC), but not in prefrontal/frontal cortex, this was partially accounted for by increased Thr(286) phosphorylation, suggesting the involvement of different mechanisms of activation. In synaptosomes, all drugs reduced the kinase phosphorylation, particularly in HC where, upon fractionation of the synaptosomal particulate into synaptic vesicles and membranes, we found that the drugs induced a redistribution and differential activation of the kinase between membranes and vesicles. Furthermore, a large decrease in the level and phosphorylation of synapsin I located at synaptic membranes was consistent with the observed decrease of CaM kinase II. Overall, antidepressants induce a complex pattern of modifications in distinct subcellular compartments; at presynaptic level, these changes are in line with a dampening of glutamate release. PMID- 17356572 TI - Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. AB - The mechanism of action responsible for the motor depressant effects of cannabinoids, which operate through centrally expressed cannabinoid CB1 receptors, is still a matter of debate. In the present study, we report that CB1 and adenosine A2A receptors form heteromeric complexes in co-transfected HEK-293T cells and rat striatum, where they colocalize in fibrilar structures. In a human neuroblastoma cell line, CB1 receptor signaling was found to be completely dependent on A2A receptor activation. Accordingly, blockade of A2A receptors counteracted the motor depressant effects produced by the intrastriatal administration of a cannabinoid CB1 receptor agonist. These biochemical and behavioral findings demonstrate that the profound motor effects of cannabinoids depend on physical and functional interactions between striatal A2A and CB1 receptors. PMID- 17356573 TI - Chronic blockade or constitutive deletion of the serotonin transporter reduces operant responding for food reward. AB - The therapeutic effects of chronic selective serotonin reuptake inhibitors (SSRIs) are well documented, yet the elementary behavioral processes that are affected by such treatment have not been fully investigated. We report here the effects of chronic fluoxetine treatment and genetic deletion of the serotonin transporter (SERT) on food reinforced behavior in three paradigms: the progressive ratio operant task, the concurrent choice operant task, and the Pavlovian-to-Instrumental transfer task. We consistently find that chronic pharmacological blockade or genetic deletion of SERT result in similar behavioral consequences: reduced operant responding for natural reward. This is in line with previous studies reporting declines in operant responding for drugs and intracranial self-stimulation with fluoxetine treatment, suggesting that the effect of SERT blockade can be generalized to different reward types. Detailed analyses of behavioral parameters indicate that this reduction in operant responding affect both goal-directed and non-goal-directed behaviors without affecting the Pavlovian cue-triggered excessive operant responding. In addition, both pharmacological and genetic manipulations reduce locomotor activity in the open field novel environment. Our data contrast with the effect of dopamine in increasing operant responding for natural reward specifically in goal-directed behaviors and in increasing Pavlovian cue-triggered excessive operant responding. Serotonin and dopamine have been proposed to serve opposing functions in motivational processes. Our data suggest that their interactions do not result in simple opponency. The fact that pharmacological blockade and genetic deletion of SERT have similar behavioral consequences reinforces the utility of the SERT null mice for investigation of the mechanisms underlying chronic SSRIs treatment. PMID- 17356574 TI - Clozapine and haloperidol differently suppress the MK-801-increased glutamatergic and serotonergic transmission in the medial prefrontal cortex of the rat. AB - The administration of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine and ketamine has been shown to increase the extracellular concentration of glutamate and serotonin (5-HT) in the medial prefrontal cortex (mPFC). In the present work, we used in vivo microdialysis to examine the effects of the more potent noncompetitive NMDA receptor antagonist, MK-801, on the efflux of glutamate and 5-HT in the mPFC, and whether the MK-801 induced changes in the cortical efflux of both transmitters could be blocked by clozapine and haloperidol given systemically or intra-mPFC. The systemic, but not the local administration of MK-801, induced an increased efflux of 5-HT and glutamate, which suggests that the NMDA receptors responsible for these effects are located outside the mPFC, possibly in GABAergic neurons that tonically inhibit glutamatergic inputs to the mPFC. The MK-801-induced increases of extracellular glutamate and 5-HT were dependent on nerve impulse and the activation of mPFC AMPA/kainate receptors as they were blocked by tetrodotoxin and NBQX, respectively. Clozapine and haloperidol blocked the MK-801-induced increase in glutamate, whereas only clozapine was able to block the increased efflux of 5-HT. The local effects of clozapine and haloperidol paralleled those observed after systemic administration, which emphasizes the relevance of the mPFC as a site of action of these antipsychotic drugs in offsetting the neurochemical effects of MK-801. The ability of clozapine to block excessive cortical 5-HT efflux elicited by MK-801 might be related to the superior efficacy of this drug in treating negative/cognitive symptoms of schizophrenia. PMID- 17356575 TI - Antiplatelet properties of escitalopram in patients with the metabolic syndrome: a dose-ranging in vitro study. AB - There is an increasing body of evidence suggesting that selective serotonin reuptake inhibitors exhibit clinical benefit beyond treating depression, by simultaneously inhibiting platelet activity. We recently demonstrated that escitalopram (ESC), but not its major metabolites, inhibits multiple platelet biomarkers in healthy volunteers. Considering that the metabolic syndrome represents one of the major risk factors for vascular disease, we here determined how ESC affects platelet activity in such patients. We assessed the in vitro effects of preincubation with escalating (50-200 nM/l) concentrations of ESC on platelet aggregation, expression of major surface receptors by flow cytometry, and quantitatively by platelet function analyzers. Blood samples were obtained from 20 aspirin-naive patients with documented metabolic syndrome. Pretreatment of blood samples with medium (150 nM/l), or high (200 nM/l) doses of ESC resulted in a significant inhibition of platelet aggregation induced by ADP (p=0.007) and by collagen (p=0.004). Surface platelet expression of GPIb (CD42, p=0.03), LAMP-3 (CD63, p=0.04), and GP37 (CD165, p=0.03) was decreased in the ESC-pretreated samples. Closure time by the PFA-100 analyzer was prolonged after the 200 nM/l dose (p=0.02), indicating platelet inhibition under high shear conditions. On the other hand, the lowest tested concentration of ESC (50 nM/l) did not affect platelet activity in these patients. The in vitro antiplatelet characteristics of ESC in patients with the metabolic syndrome are similar to those in healthy volunteers. However, higher ESC doses are required to induce equally potent platelet inhibition. These data justify prospective ex vivo studies with the highest therapeutic dose to determine the potential clinical advantage of ESC in high-risk patients with vascular disease. PMID- 17356576 TI - SB-649915-B, a novel 5-HT1A/B autoreceptor antagonist and serotonin reuptake inhibitor, is anxiolytic and displays fast onset activity in the rat high light social interaction test. AB - Preclinically, the combination of an SSRI and 5-HT autoreceptor antagonist has been shown to reduce the time to onset of anxiolytic activity compared to an SSRI alone. In accordance with this, clinical data suggest the coadministration of an SSRI and (+/-) pindolol can decrease the time to onset of anxiolytic/antidepressant activity. Thus, the dual-acting novel SSRI and 5 HT(1A/B) receptor antagonist, SB-649915-B, has been assessed in acute and chronic preclinical models of anxiolysis. SB-649915-B (0.1-1.0 mg/kg, i.p.) significantly reduced ultrasonic vocalization in male rat pups separated from their mothers (ED(50) of 0.17 mg/kg). In the marmoset human threat test SB-649915-B (3.0 and 10 mg/kg, s.c.) significantly reduced the number of postures with no effect on locomotion. In the rat high light social interaction (SI), SB-649915-B (1.0-7.5 mg/kg, t.i.d.) and paroxetine (3.0 mg/kg, once daily) were orally administered for 4, 7, and 21 days. Ex vivo inhibition of [(3)H]5-HT uptake was also measured following SI. SB-649915-B and paroxetine had no effect on SI after 4 days. In contrast to paroxetine, SB-649915-B (1.0 and 3.0 mg/kg, p.o., t.i.d.) significantly (p<0.05) increased SI time with no effect on locomotion, indicative of an anxiolytic-like profile on day 7. Anxiolysis was maintained after chronic (21 days) administration by which time paroxetine also increased SI significantly. 5-HT uptake was inhibited by SB-649915-B at all time points to a similar magnitude as that seen with paroxetine. In conclusion, SB-649915-B is acutely anxiolytic and reduces the latency to onset of anxiolytic behavior compared to paroxetine in the SI model. PMID- 17356577 TI - Interaction between childhood trauma and serotonin transporter gene variation in suicide. AB - Although the serotonin transporter promoter polymorphism (5-HTTLPR) contributes to depression and suicidality in a fashion modulated by environmental stress, 5 HTTLPR has been little examined in relation to suicidal behavior in substance dependence. Recently, a third functional allele of 5-HTTLPR was discovered enabling more of the interindividual variation in serotonin transporter expression to be predicted by genotype. We examined whether the 5-HTTLPR gene alone, or interacting with childhood trauma, was predictive of suicidal behavior in substance-dependent patients, a clinical population that is at high risk of suicide, as well as childhood trauma and other stress. We interviewed 306 abstinent male African-American substance-dependent patients about whether they had ever attempted suicide and administered the 34-item Childhood Trauma Questionnaire (CTQ). Patients and 132 male African-American controls were genotyped to determine the S, L(G), and L(A) 5-HTTLPR alleles; some analyses grouped the S and L(G) alleles on the basis of equivalent function. The distribution of 5-HTTLPR genotypes did not differ between patients and controls, nor between suicide attempters and non-attempters. However, patients with low expression 5-HTTLPR genotypes and above-median CTQ scores were more likely to have attempted suicide. Logistic regression showed increasing risk of a suicide attempt with increasing reports of childhood trauma scores; in addition, this increase was exaggerated among those with low expression forms of the 5-HTTLPR genotype. Childhood trauma interacts with low expressing 5-HTTLPR genotypes to increase the risk of suicidal behavior among patients with substance dependence. PMID- 17356578 TI - The folding and evolution of multidomain proteins. AB - Analyses of genomes show that more than 70% of eukaryotic proteins are composed of multiple domains. However, most studies of protein folding focus on individual domains and do not consider how interactions between domains might affect folding. Here, we address this by analysing the three-dimensional structures of multidomain proteins that have been characterized experimentally and observe that where the interface is small and loosely packed, or unstructured, the folding of the domains is independent. Furthermore, recent studies indicate that multidomain proteins have evolved mechanisms to minimize the problems of interdomain misfolding. PMID- 17356579 TI - Netrins: beyond the brain. AB - Named after the Sanskrit word netr, which means 'one who guides', the netrin family of secreted proteins provides migrational cues in the developing central nervous system. Recently, netrins have also been shown to regulate diverse processes (such as cell adhesion, motility, proliferation, differentiation and, ultimately, cell survival) in a number of non-neuronal tissues. In some cases, netrins affect these functions through non-classic netrin receptors, prompting a renewed interest in these factors in and beyond the nervous system. PMID- 17356580 TI - Antioxidant Effects of Vitamins C and E on Phenylhydrazine-Induced Haemolysis in Sprague Dawley Rats: Evidence for A better Protection by Vitamin E. AB - BACKGROUND: Phenyldrazine (PHDZ) provokes acute haemolysis and generates free radicals that are known to be involved in the toxicity of the drug. Vitamin C and E have been ascribed beneficial roles in many acute haemolytic states and oxidative stress. OBJECTIVE: The present study was designed to assess the antioxidant effect of vitamin C and E on PHDZ- induced haemolysis in SD rat in vivo and ex-vivo. METHOD: Rats treated for weeks with oral vitamin E (500mg/kg/day, n=6), oral vitamin C (100mg/kg/day, n=6) and control rats, which received tap water; were monitored for peripheral blood parameters and haemolytic activity of erythrocytes at Baseline, 48 hours and 1 week respectively after intraperitonial administration of PHDZ (15mg/kg/day for 7 days). Osmotic fragility as well as organ weights were determined 1 week after PHDZ. Dose dependent effects of vitamins C and E on haemolysis were determined at the end of 120 min incubation of rat RBC with the vitamins in phosphate-buffered-saline. RESULTS: Hb and PCV were better preserved in rats pre-treated with the antioxidants. The spleenomegaly, cardiomegaly and hepatomegaly associated with PHDZ treatment were significantly reduced in antioxidant pre-treated rats (P<0.001). reduction in cardiac weight was more marked in vitamin E group (0.56+/ 0.02g vs. 0.72+/-0.03g; n=6; P<0.01; vitamin E vs. PHDZ) compared to vitamin C (0.69+/-0.02g vs. 0.72+/-0.03g; n=6; P>0.05; vitamin C compared to PHDZ). RBC of vitamin E group exhibited better resistance to osmoticlysis (P<0.001). at higher doses (400-500mg/L), vitamin C caused significant haemolysis both in the absence (P<0.001) and presence of PHDZ (P<0.001). Vitamin E abolished the long tail of the osmotic fragiligram. CONCLUSION: The result of this study suggests that compared to vitamin C, vitamin E may better protect RBC against haemolysis induced by oxidative stress. PMID- 17356581 TI - Attitude of nigerian resident doctors towards clinical autopsy. AB - BACKGROUND: It is to the disadvantage of the doctors in training that there is a decline in the rate of clinical autopsy world wide. This decline may to an extent depend on the attitude of the physicians. AIM: To evaluate the attitude of resident doctors towards the practice of clinical autopsy and to determine their role in the decline of clinical autopsy. METHOD: We carried out a survey of the attitude of resident doctors undergoing training in the various clinical departments of our teaching hospital towards clinical autopsy practice. This survey was by means of a structured randomly distributed questionnaire. Questions were asked on their willingness to request for autopsy, the number of autopsies that they have requested for so far, what hinders them from requesting for autopsy, the level of participation at autopsy and the importance of autopsies in the health care delivery system RESULTS: Eighteen (30%) out of 60 resident doctors attributed their inability to request for autopsy on their not being in direct control of the patients, while 16 (26.7%) found it difficult to get consent from the relatives. Seventeen per cent of them gave reason of not being able to obtain report from the pathologist, 13.3% said it was difficult to get pathologist to perform autopsy on time while only 11% said they knew the diagnosis in most of their cases. Almost all the resident doctors (98.5%) agreed that autopsy is a necessary procedure and is important for their training and health care delivery system CONCLUSION: Autopsy rate can increase if the resident doctors receive more blessings to request for autopsy from their consultants. Increased exposure to autopsies and education with regards to the benefits of autopsies at both the undergraduate and post graduate level will contribute to improvement in the rate of clinical autopsy. PMID- 17356582 TI - Environmental sanitation in an urban community in benin city, edo state. AB - OBJECTIVES: To assess the sanitary conditions in an urban community in Benin City, Edo State. METHODS: A cross-sectional descriptive study using multi-staged sampling method. Data collection was by means semi-structured researcher administered questionnaires. Intervention in the form of health education was carried out among the respondents on various environmental sanitation issues. Data was analysed using the Computer Programme for Epidemiologists (PEPI). RESULTS: A majority 213(50.4%) of the respondents obtained their water from private boreholes while 93(22.0%) obtained irregular pipe-borne water supplies from the public utility board, with only 160(37.8%) having adequate supplies and 291(68.8%) not using any form of water purification methods. 321(75.8%) of the respondents used the water closet for sewage disposal though these toilets were not flushed after every use in 70.7% of cases. The commonest methods of refuse disposal were open dumping (59.0%) and burning (26.4%). Indices of personal hygiene practices were high (average 87.8%), though the proportions of respondents who used soap for hand washing were all lower than those of hand washing without soap. Vector and pest control were mainly by the use of mosquito nettings of doors and windows (30.4%) and fumigation (18.8%). CONCLUSION: The overall level of sanitation is unsatisfactory. There is therefore need for intensive and continued health education to address these deficiencies. PMID- 17356583 TI - Euthyroid Sick syndrome And Cardiac Failure In Zaria, Nigeria. AB - AIMS AND OBJECTIVES: The study was aimed at establishing the existence of sick euthyroid syndrome in our patients with cardiac failure and to find out whether the syndrome in the our patients has a peculiar pattern PATIENTS AND METHODS: Thirty subjects diagnosed with cardiac failure in NYHA class 3 and 4 were studied; they had clinical evaluation, electrocardiograph, chest radiograph and echocardiograph. The biochemical investigation included urea, electrolyte, and creatinine, thyroid function test (T3, T4 and TSH). Thirty individuals who served as control (age and sex matched) also had similar evaluation to the subjects. RESULTS: The subjects' ages ranging from 17 to 85 years and a mean of 51.0 +/- 15.8 years compared to controls with a mean age of 48.9 +/- 8.1 years (p < 0.1). Twenty-two and eight patients were in NYHA class3 and 4 respectively. The subjects had a lower mean T3 than controls of 1.42 +/- 0.07 ug/l and 2.3 +/- 1.0 ug/l respectively and p < 0.001. The mean T4 levels were higher in the subjects than controls (85.4 +/- 26 ug/l and 70.0 +/- 1.7 ug/l respectively and p < 0.001) but TSH levels were similar in the two groups. The subjects had higher mean values of LAD, aortic root diameter, IVSD, LVIDD, LVPW, EDV ESV, LVM and LVMI (p < 0.05). The LV ejection fraction and fractional shortening were lower in subjects than controls (p <0.01). Six, seventeen and seven subjects had diastolic, systolic and combined diastolic-systolic dysfunction on echocardiography respectively. There was a positive correlation between T3 with duration of cardiac failure and ejection fraction (p < 0.05). There was a negative correlation between T3 and LVM, LVMI, LVIDD, EDV, LAD and cardio thoracic ratio. The levels of T4 showed a positive relationship with LAD and CTR. Partial correlation was statistically significant between T3 and duration of cardiac failure, duration of aetiology of cardiac failure and LVM. The various forms of cardiac failure (diastolic, systolic and combined diastolic-systolic dysfunction) showed no statistically significant difference in mean levels of T3, T4 and TSH. CONCLUSION: Euthyroid sick syndrome is also seen in Nigerians with cardiac failure as reported elsewhere and the levels of T3 seemed to be inversely proportional to LAD, CTR, LVIDD, LVM and LVMI. Serum T3 levels are also directly proportional to EF and FS. Low serum levels of T3 with normal T4 and TSH is associated with severe cardiac failure. PMID- 17356584 TI - Sexual behaviour and associated risk factors among adolescent/ young adult male transport workers at yaba bus stop, lagos. AB - OBJECTIVES: Sexual activity is increasing among young people with negative consequences and out of school males are a vulnerable segment of the population. This study was carried out to examine the sexual behaviour of young males who are out of school and identify factors that influence their behaviour. METHODS: This descriptive study was conducted among all the three hundred and ninety one young male bus conductors and drivers at Yaba bus stop Lagos. They were interviewed using a structured questionnaire. RESULTS: Almost all the respondents (93.4%) have had sexual intercourse and many of them with multiple partners. Less than half of them used condoms at every intercourse. Their main reasons for initiating sexual intercourse were peer pressure and curiosity. There was a significant relationship between early initiation of sexual intercourse and use of drugs and alcohol(p<0.05).Respondents who have resided with their parents initiated intercourse at an older age than those residing with other people.(p<0.05) CONCLUSION: Many young out of school males are sexually active and engage in high risk sexual behaviour. Provision of sexuality education programmes, co-habitation of parents with their young children and the control of use of alcohol and drugs are important in delaying sexual initiation and reducing sexual risk taking among young people. PMID- 17356585 TI - Plasma magnesium and calcium levels in children with epilepsy in lagos. AB - BACKGROUND: Magnesium and calcium have been found to have increasing roles in the patho-physiology of epilepsy. Hypomagnesaemia and hypocalcaemia cause hyper exitability of neurons and have been associated strongly with seizures in adults and children. OBJECTIVES: To determine if hypomagnesaemia or hypocalcaemia is present in Nigerian children with epilepsy and to determine the relationship between serum magnesium and calcium levels and frequency and control of epilepsy. DESIGN: A prospective case control study at the Lagos University Teaching Hospital. PATIENTS AND METHODS: 45 children with epilepsy and 45 controls were recruited from the paediatric neurology unit of the Lagos University Teaching Hospital. Serum magnesium and calcium were measured by spectrophotometric methods. RESULTS: Serum magnesium and calcium was significantly lower in the patients compared to the controls; Magnesium - 0.98 (0.0005) Vs 1.2 (0.04) mmol/L, p< 0.0001 and Calcium - 2.29 (0.04) Vs 2.3 (0.02) mmol/L, p<0.05 respectively. No significant differences were noted in the plasma phosphorus and albumin concentrations. CONCLUSION: Magnesium and calcium levels are lower in the epileptic children compared to the controls during the seizure-free periods. More studies are needed to evaluate these electrolytes during seizures and the effect of the different anticonvulsant drugs on these electrolytes. PMID- 17356586 TI - Comparative study of the effect of tocotrienols and -tocopherol on fasting serum lipid profiles in patients with mild hypercholesterolaemia: a preliminary report. AB - OBJECTIVES: Hypercholesterolaemia is a risk factor for cardiovascular diseases. Tocotrienols reportedly possess hypocholesterolaemic activity. This study examined the effect of tocotrienols (T3) in TOCOVIDTM Suprabio TM on serum lipids. Patients and Methods :A randomised (2:1), open-label study of patients with mild hypercholesterolaemia (= 5.18mmol/L to <7.77mmol/L) and one additional cardiovascular risk factor was carried out. Subjects received either tocotrienols (as TOCOVIDTM Suprabio TM ) (n=28) or vitamin E (a-tocopherol) 500mg daily (n=16). Fasting lipids were compared at baseline and after 4 weeks therapy. RESULTS: Following 4 weeks therapy, mean +/- SD total cholesterol declined significantly in the tocotrienol group (from 6.10+/-0.66 to 5.47+/-1.16; P=0.02) compared to the a-tocopherol group (from 5.92+/-0.52 to 5.47+/-0.76; P>0.05). Mean LDL-C levels (mmol/L) were also significantly reduced in the tocotrienol group (3.82+/-0.85 to 3.24+/-1.26; P=0.04), but not in those on a-tocopherol (3.84+/-0.75 to 3.28+/-0.94; P>0.05). There were no significant changes in HDL-C and triglycerides in both groups. The tocotrienol group experienced a net decline in TG (7.1+/-31.4 %; P>0.05) while the a-tocopherol group had a net increase at week 4 (38.6+/-61.7%; P>0.05). CONCLUSION: The study adds to existing evidence of the favourable effect of tocotrienols on total cholesterol and LDL-C. However, the results need further evaluation. PMID- 17356587 TI - Prevalence of Poor Glycaemic Control in Diabetics seen in a Tertiary Medical Centre. AB - OBJECTIVE: The objective of the study was to determine the prevalence of poor glycaemic control in otherwise clinically stable diabetic patients seen in a tertiary hospital. STUDY DESIGN: It was a cross-sectional study of 64 type 2 diabetic patients and 32 healthy controls. Patients were randomly selected from registered diabetic patients of the hospital who came to the pathology phlebotomy room for routine fasting plasma glucose investigation; (prior to their regular diabetic clinic attendance). The controls were selected from amongst hospital workers and clients of the hospital on routine medical investigations. The fasting plasma glucose and glycated haemoglobin were estimated, so also was urinalysis. The mean, standard deviation and standard error of mean (SEM) were calculated, so also were the frequency and percentages. Student ' t ' test method was applied as test of statistical significance. RESULTS: 53.2% of the patients had good glycaemic control, 31.2% fair and 15.6% poor glycaemic control. 46.9% glycosuria, 34.4% proteinuria and 9.4% ketonuria. 31.8% had no formal education and 46.9% had no knowledge of the type of drugs they were taking for the disease. CONCLUSION: The prevalence of poor glycaemic control is high in type 2 DM patients seen in our hospital. More regular monitoring of FPG and glycated haemoglobin is recommended. PMID- 17356588 TI - Substance use Among University Undergraduates: A Study of Pattern and Beliefs in Ile-Ife. AB - OBJECTIVES: To determine the prevalence of substance use and to investigate the relationship between psychosocial variables and current use of psychoactive substances among university undergraduates. METHODS: A cross-sectional survey of randomly selected undergraduates of the Obafemi Awolowo University, Ile Ife was carried out using the WHO drug use questionnaire. RESULTS: Alcohol, stimulants, hypnosedatives, tobacco and cannabis with current use prevalence rates of 20.2 %, 17.7%, 9.8%, 9.0% and 8.2 % respectively were the most commonly used substances. Inhalants/organic solvents, cocaine, heroin, hallucinogens and pethidine/morphine with current use rates of 3.2%, 2.6%, 2.2%, 1.0% and 0.5% respectively belonged to the 'low - use' category. However, these rates were marginally higher than most previous findings. Five variables (sex, polygamy, living outside the university campus, poor mental health and study difficulty), were significantly associated with the use of many of the substances. Also, perceived harmfulness was observed to be a possible deterrent to substance use and most users were engaged in the use of cheap and easily available substances. CONCLUSION: The observations are largely similar to those from other locations in Nigeria and may therefore be useful in preventive programmes. PMID- 17356589 TI - The causes and outcomes of cancellation of orthopaedic surgeries at the obafemi awolowo university teaching hospital complex ile-ife, Nigeria. AB - BACKGROUND: Cancellation of cases on the scheduled day of surgery leads to an inefficient utilisation of scarce hospital and patient's resources. Identifying the causes of such cancellations will assist in taking steps to avoid them. METHODS: This is a retrospective study spanning 10 years. Record was taken of all patients who had orthopaedic surgery at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife Nigeria. The age, sex, type of operation, whether or not the surgery was ever postponed or cancelled, the duration and reasons for such postponements and the duration of admission were collated and analysed. RESULTS: Five hundred and fifty two (40.8%) of the 1,353 orthopaedic patients scheduled for surgery experienced cancellation. The most common reasons were attributable to the hospital (48.7%) mainly due to infrastructural breakdown (28.7%) and procedural lapses by hospital personnel (20.0%). Self cancellation by patient (37.8%) followed and was mainly due to financial constraints (25.6%). Upper respiratory tract infections were responsible for the cancellation in 8.6%. These delays were responsible for more than 30% of the duration of admission in 93 (16.8%) patients. CONCLUSION: The incidence of postponement of cases on the scheduled day of surgery is still high. Most of the causes are preventable. Better infrastructural facilities, enhanced interdepartmental communication and improved attitude to work would reduce the rate and thus enhance utilisation of theatre space. PMID- 17356590 TI - Risk factors for cancer of the cervix. AB - BACKGROUND: Cancer of the cervix is the second most common cancer among women worldwide and the leading cancer in Nigeria. OBJECTIVE: This study examined the risk factors associated with cancer of the cervix as seen in patients presenting to a tertiary hospital with gynaecologic conditions. STUDY DESIGN: The case control study design was used with a retrospective review of records of randomly selected cases of cancers of the cervix from the cancer registry and appropriate controls among hospital patients. RESULTS: Binary logistic regression carried out on the data revealed that contraceptive method (OR = 3.38, 95% CI = 1.75, 6.51) number of children (OR = 1.27, 95% CI = 1.09, 1.47), and age (OR = 1.07, 95% CI = 1.05, 1.10) were the significant risk factors out of all the potential risk factors that were assessed. CONCLUSION: These findings provide a useful insight into the general pattern of risk associated with cancer of the cervix in our environment. PMID- 17356591 TI - Management Of Urethral Strictures In The UCTH Calabar. AB - Forty-five consecutive cases of urethral stricture seen in a single unit over a three-year period (May 2000-April 2003) were studied to determine mode of presentation, symptoms on presentation, cause of the stricture, course of the illness and the outcome of treatment. Thirty-nine patients were treated while 6 were lost to follow up before definitive therapy could be given. Most of the patients were adult males in their prime of life. Strictures were as a result of urethritis in 24 (53.3%) cases, trauma in 16 (35.6%) cases, indwelling catheter in 3 (6.6%) cases and of uncertain aetiology in 2 (4.4%) cases. Three of the post traumatic cases were post prostatectomy. Definitive treatment was by urethroplasty in 28 (62.2%) patients, bouginage in 11 (24.4%) patients.. Results of treatment were classified as 'GOOD' or 'POOR' based on patients' judgement of improved flow, observed improvement of flow and comparison of urethrogram results, before and after treatment. Of the 28 patients treated by urethroplasty, 21 (75%) had 'GOOD' outcome while in 7 patients (25%) the outcome was 'POOR'. In the bouginage group, outcome was 'GOOD' in 63.6% (7/11) of patients, 'POOR' in 27.3% (3/11), while one patient died from septic complications. It is concluded that urethroplasty gives overall, better results in management of strictures, but dilatation remains a viable option in carefully selected cases and that urethritis is still a foremost aetiological factor for urethral strictures in Calabar. PMID- 17356592 TI - Ophthalmic mortality in a tertiary centre in Nigeria. AB - OBJECTIVES: To determine the mortality rate of ophthalmic ward patients and the causes of death. METHODS: A retrospective study of all ophthalmic patients admitted into the ophthalmic wards of the University of Benin Teaching Hospital, Benin City between May 1989 and April 2005 was conducted. The case records of all ophthalmic deaths were analysed. The age, sex, diagnosis and cause of death were recorded. RESULTS: A total of 1854 patients were admitted into the ophthalmic ward comprising 1,057 males (57%) and 797 females (43%) giving a male-to-female ratio of 1.3:1. There were 7 deaths in the ophthalmic wards during the period giving a mortality rate of 3.8/100 admission. Three patients (42.8%) were being managed for orbital cellulitis, 2 patients (28.6%) had malignant tumours and the remaining 2 patients (28.6%) had cataract extraction. CONCLUSION: The mortality rate in the ophthalmic ward was low. Deaths could be prevented by early presentation, adequate preoperative screening, good nursing care, high index of suspicion by clinicians and provision of affordable drugs for life-threatening conditions. PMID- 17356593 TI - Malignant Breast Lessions At Olabisi Onabanjo University Teaching Hospital (O.O.U.T.H), Sagamu-a Histopathological Review. AB - Various reports suggest an increasing incidence of breast cancer in Nigeria. The large volume of literature published on the subject of breast cancer bear witness to the interest shown in the subject. We therefore carried out a review of 50 cases of breast cancer recently confirmed histologically by our unit to study their characteristics and compare these with previous reports. A 2- years retrospective review of all histologically diagnosed carcinoma of the breast at Olabisi Onabanjo University Teaching Hospital, Sagamu from 2002-2003 was carried out. The peak age of occurrence was between 40-49 years with mean age of 47.5years. Invasive ductal carcinoma was predominant histologic type in 94% of cases and 72% presented late with advanced disease (Manchester stages 111 and 1V) with dismal prognosis. Surgery was the mainstay of treatment for both early and late disease. To ensure early and prompt detection, presentation and treatment, emphasis should be placed on female education, increasing awareness and encouraging breast self-examination. There is also a need for cancer registration centre in the hospital and a multicentred, controlled study of breast cancer in Nigeria. PMID- 17356594 TI - A-5 year review of cerebral malaria in nigerian children. AB - BACKGROUND: Cerebral malaria is thought to be common in the under fives in a malaria holoendemic region like ours. But we are recently seeing cases of cerebral malaria in children older than 5 years. This study was carried out to determine the Morbidity And Mortality Pattern Of Cerebral Malaria. MATERIALS AND METHODS: This was a retrospective review of cases of cerebral malaria seen over a five-year period (1999-2003) at the Paediatrics Department of the Obafemi Awolowo University Teaching Hospital Complex Ile-Ife. All case notes of patients admitted with a diagnosis of cerebral malaria were retrieved and relevant data extracted to a standard form. RESULTS: One hundred and fifty four (154) patients were managed as cerebral malaria, out of a total of 5,456 admissions over this period. Eighteen were aged less than one year, 128 were aged 1-5 years while eight were aged >5 years. Eight of the 154 patients died (5.2%). However 16 (10.3%) had various neurological deficits at discharge. CONCLUSION: Cerebral malaria is still a major complication of malaria in our practice and it is no longer a problem of under-five children alone. PMID- 17356595 TI - Performance at the national postgraduate medical college fellowship examinations in dental surgery- a 23 year review. AB - OBJECTIVES: This study evaluates the performances at various levels of examinations from inception as a guide to the assessing how far the Faculty has been able to meet the objectives for which it was established and offer recommendations for repositioning the Faculty for future development. MATERIALS AND METHODS: Results of the Fellowship examinations of the Faculty of Dental Surgery in the three examination levels from 1979 to 2002 (FMCDS) were retrieved. The data were analysed for gender, sub specialties of preference, number of attempts at Parts I and II levels and average duration of completion of the Fellowship programme. RESULTS: Between 1979-2002, 633 candidates sat for the Primary FMCDS examination, 262 (41%) were successful. In the Part I FMCDS examination 330 candidates sat for the examination from 1980-2002. 128 (39%) were successful, while at the Part II level 77 candidates sat for the examination, 43 (56%) were successful and 34 (44%) failed. 57(44.5%) and 30 (69.8%) passed the Part I & II respectively at first attempt, while 27 (21.1%) and 10 (23.3%) were successful in the Parts I and II respectively at the 2nd attempt. 39 (30.5%) and 5 (3.9%) were successful in the Part I examination at 3rd and 4th attempts, while 3(7.0%) were successful in the Part II FMCDS at 3rd attempt. The duration of training ranged from 6-7 years in over 50% of the candidates, mean of 7.5 years overall. CONCLUSION: The Faculty of Dental Surgery has had tremendous impact on the dental manpower need of the nation within the period under review. PMID- 17356596 TI - Two decades of minilaparotomy female sterilisation at the university of benin teaching hospital. AB - OBJECTIVE: To evaluate female sterilisation through minilaparotomy approach in University of Benin Teaching Hospital over a 20-year period. STUDY DESIGN, SETTING AND SUBJECTS: This was a retrospective study in which the case notes of 156 clients who accepted permanent method of contraception out of 14771 acceptors of family planning methods in the University of Benin Teaching Hospital between January 1985 and December 2004 were retrieved and analyzed for socio-demographic characteristics of the clients, timing, technique, type of anaesthesia used and the complications associated with the procedure. RESULTS: The incidence of female sterilisation was 1%, mean age and parity were 36.9 +/- 3.6years and 6.4 +/- 1.6 respectively. 80.8% had interval sterilisation and the tubal occlusion was mainly by Pomeroy's technique. Local anaesthesia under heavy sedation was used in 85.9% of the clients. Surgical complications occurred in 3.24% and were uterine perforation, bladder and intestinal injuries and bleeding from the fallopian tube and the mesosalpinx. 3.85% had wound infection and 1.94% anaesthetic complications. Effectiveness was 100% and there was no mortality. CONCLUSION: Our institution would need to scale up counseling of clients for permanent method of contraception to improve on the poor acceptability. Careful surgical techniques with local anaesthesia alone or with light sedation and adherence to infection prevention practices would reduce the incidence of surgical, anaesthetic complications and wound sepsis that would ensure client satisfaction. PMID- 17356597 TI - Surgery of parotid gland tumours in lagos: a 12 year review. AB - BACKGROUND/AIM: Tumours of the parotid gland are not common. Parotid tumours can pose a challenge both in diagnosis and treatment. Various factors contribute to the management difficulties of parotid tumours for the Head neck surgeon. The aim of the study is to determine the presentation and management of parotid tumours requiring surgery at the Burns and Plastic and Otolaryngology (ORL) units of the hospital. MATERIALS AND METHODS: This is a retrospective study carried out at the Lagos University Teaching Hospital from January 1994- December 2005. The medical case notes were reviewed for information on age, sex, clinical presentation, surgical management, histological diagnosis and outcome. RESULTS: A total of 58 patients with parotid tumours were seen with ages ranging from 25-65 years. Male to Female ratio was 1.4:1. Forty-two (72.4%) presented with firm preauricular swelling, 1.7% as dumb bell tumour and post surgical recurrence tumour respectively, 6.8% as tail of parotid tumour and 3.5% as bilateral disease. 93.13% had superficial parotidectomy. Histological diagnosis confirmed 65.5% as pleomorphic adenoma, 20.72% as carcinomas of which adenoidcystic and mucoepidermoid tumours were the commonest,3.45% as lymphoma and 1.7% as Sjogrens syndrome, oxyphil and Warthins tumour respectively. Immediate post surgical facial nerve palsy was seen in 69% and recovery was seen in 62% within 3-9months. Post surgical radiotherapy was given to 8.6%. CONCLUSION: The commonest parotid salivary gland tumour requiring surgery is pleomorphic adenoma, presenting as a pre-auricular mass and the commonest post- surgical complication was facial nerve palsy involving the mandibular branch. A good knowledge of the surgical anatomy of the gland, clinical behaviour and biologic nature of the tumours will ensure better surgical management. PMID- 17356598 TI - Hereditary wide angle exotropia in a nigerian family. AB - AIM: To present a report of a Nigerian family with wide angle exotropia resulting in amblyopia. METHODS: A family of two wives and 12 children from Benin City, Edo State, Nigeria were interviewed and examined at the University of Benin Teaching Hospital, Benin City with the aid of a Snellen's chart, pen torch, slit lamp biomicroscope, ophthalmoscope and the pulsair non-contact tonometer. RESULTS: There was 450 exotropia in the right eye of the 72 year old father, his 36 year old son, his 22 years old daughter and their 24 year old half sister. There was restriction of ocular motility in the right eye medially and some degree of amblyopia in the right eye of all the patients. The father and his 22 years old daughter were myopic of between -4.00 and -6.00 dioptre sphere but the son and his 24 years old half sister had -0.75 and -1.00 dioptre sphere myopia respectively. None of them presented to hospital because of the strabismus. CONCLUSION: This report highlights the need to screen family members of patients with squint in order to detect the condition early and prevent amblyopia. PMID- 17356599 TI - Available and affordable pre-definitive surgical management of symblepharon in end stage stevens johnson syndrome: a case report. AB - We describe an affordable, easily available technique to relieve discomfort, free the eyeball and partially rehabilitate a patient with ocular complications of end stage Stevens Johnson syndrome. MATERIAL AND METHODS: Two eyes of a patient with severe adhesions between the lids, bulbar conjunctiva and cornea were involved. After taking consent from patient, the adhesions were separated and the fornices were dressed with sofratulle and artificial lubricants until healing was complete. DISCUSSION: The separation of the lids from the globe and prevention of contact between the ocular surface and tarsal conjunctiva until both are healed by sofratulle and lubricants happens to be the only choice in our environment without material and human resources for complex procedures such as submandibular autotransplantation, osteo-odonto keratoprosthesis and modified cutler beard flap. The use of amniotic membrane transplantation (AMT) was also not feasible at that time. RESULTS: The visual acuity was hand movement in both eyes, the lids were free and the eyes remained freely mobile four weeks after surgery. CONCLUSION: In an environment with little resources, our procedure is recommended for use as an initial procedure pending final rehabilitative surgery, as it is easily available and affordable. PMID- 17356601 TI - Controlled Monte Carlo method for light propagation in tissue of semi-infinite geometry. AB - The controlled Monte Carlo method is generalized to model photon migration in turbid media of arbitrary geometries. Its implementation for the reflection geometry is exemplified in this paper. The most probable diffuse direction of light is used as the local attractive vector that serves as the basis of biased sampling of scattering angles. Consequently, path-length resolved photon trajectories can be generated with a significantly improved efficiency. We report a more than 29 times reduction in simulation time for early arriving photons in a typical configuration. PMID- 17356602 TI - Theoretical investigation of measuring cerebral blood flow in the adult human head using bolus Indocyanine Green injection and near-infrared spectroscopy. AB - To investigate the accuracy of measuring cerebral blood flow (CBF) using a bolus injection of Indocyanine Green (ICG) detected by near-infrared spectroscopy in adult human heads, simulations were performed using a two-layered model representing the extracerebral and intracerebral layers. Modeled optical data were converted into tissue ICG concentration using either the one-detector modified Beer-Lambert law (MBLL) method, or the two-detector partial path-length (PPL) method. The CBFs were estimated using deconvolution and blood flow index techniques. Using the MBLL method, the CBFs were significantly underestimated but the PPL method improved their accuracy and robustness, especially when used as relative measures. The dispersion of the arterial input function also affected the CBF estimates. PMID- 17356603 TI - Ultrasound-modulated optical tomography with intense acoustic bursts. AB - Ultrasound-modulated optical tomography (UOT) detects ultrasonically modulated light to spatially localize multiply scattered photons in turbid media with the ultimate goal of imaging the optical properties in living subjects. A principal challenge of the technique is weak modulated signal strength. We discuss ways to push the limits of signal enhancement with intense acoustic bursts while conforming to optical and ultrasonic safety standards. A CCD-based speckle contrast detection scheme is used to detect acoustically modulated light by measuring changes in speckle statistics between ultrasound-on and ultrasound-off states. The CCD image capture is synchronized with the ultrasound burst pulse sequence. Transient acoustic radiation force, a consequence of bursts, is seen to produce slight signal enhancement over pure ultrasonic-modulation mechanisms for bursts and CCD exposure times of the order of milliseconds. However, acoustic radiation-force-induced shear waves are launched away from the acoustic sample volume, which degrade UOT spatial resolution. By time gating the CCD camera to capture modulated light before radiation force has an opportunity to accumulate significant tissue displacement, we reduce the effects of shear-wave image degradation, while enabling very high signal-to-noise ratios. Additionally, we maintain high-resolution images representative of optical and not mechanical contrast. Signal-to-noise levels are sufficiently high so as to enable acquisition of 2D images of phantoms with one acoustic burst per pixel. PMID- 17356604 TI - Frequency-domain sensitivity analysis for small imaging domains using the equation of radiative transfer. AB - Optical tomography of small imaging domains holds great promise as the signal-to noise ratio is usually high, and the achievable spatial resolution is much better than in large imaging domains. Emerging applications range from the imaging of joint diseases in human fingers to monitoring tumor growth or brain activity in small animals. In these cases, the diameter of the tissue under investigation is typically smaller than 3 cm, and the optical path length is only a few scattering mean-free paths. It is well known that under these conditions the widely applied diffusion approximation to the equation of radiative transfer (ERT) is of limited applicability. To accurately model light propagation in these small domains, the ERT has to be solved directly. We use the frequency-domain ERT to perform a sensitivity study for small imaging domains. We found optimal source-modulation frequencies for which variations in optical properties, size, and location of a tissue inhomogeneity lead to maximal changes in the amplitude and phase of the measured signal. These results will be useful in the design of experiments and optical tomographic imaging systems that probe small tissue volumes. PMID- 17356605 TI - Significance of tissue anisotropy in optical tomography of the infant brain. AB - We study the effect of tissue anisotropy in optical tomography of neonates. A Monte Carlo method capable of modeling photon migration in an arbitrary 3D tissue model with spatially varying optical properties and tissue anisotropy is used for simulating measurements of neonates. Anatomical and diffusion tensor magnetic resonance imaging of neonates are used for creating the anatomical models. We find that tissue anisotropy affects the measured signal and the pattern of sensitivity in optical measurements. PMID- 17356606 TI - Time-domain Green functions for diffuse light in two adjoining turbid half spaces. AB - Propagation of light emitted by an instantaneous source located above a plane interface between two semi-infinite turbid media is considered using the diffusion approximation. Green functions are derived for an instantaneous line source and an instantaneous point source by the method of Bellman et al. [Philos. Mag. 40, 297 (1949)], which is based on integral transforms. Both two-dimensional and three-dimensional Green functions for diffuse light have been obtained in the form of single integrals that allow for fast calculation of the specific intensity in the whole space. The influence of the optical parameters of the two media (diffusion coefficients, absorptions, and refractive indices) on the shapes of the contour lines of the specific intensity is analyzed. PMID- 17356607 TI - Sensitivity characterization of a time-domain fluorescence imager: eXplore Optix. AB - A key issue in the practical application of fluorescence imaging is the presence of a background signal detected during data acquisition when no target fluorescent material is present. Regardless of the technology employed, background signals cannot be completely eliminated, which limits the detection sensitivity of fluorescence imaging systems, especially for in vivo applications. We present a methodology to characterize the sensitivity of fluorescence imaging devices by taking the background effect into account through the fluorescent signal-to-background ratio (SBR). In an initial application of the methodology, tissuelike liquid phantoms with Cy5.5 fluorescent inclusions were investigated experimentally over a wide range of varying parameters, such as tissue absorption coefficient, scattering coefficient, fluorophore concentration, and inclusion location. By defining detectable and quantifiable SBR thresholds, empirical relations are established, and the sensitivity performance of Advanced Research Technologies's eXplore Optix using Cy5.5 is characterized. PMID- 17356608 TI - Effect of probe arrangement on reproducibility of images by near-infrared topography evaluated by a virtual head phantom. AB - The effect of the probe arrangement on the reproducibility of topographic images of the concentration changes in oxygenated hemoglobin and deoxygenated hemoglobin is evaluated by a virtual head phantom. A virtual head phantom consists of five types of tissue the 3D structure of which is based on a magnetic resonance imaging scan of an adult head. Localized and broadened brain activation is assumed in a virtual head phantom. The topographic images are obtained from the reflectance detected by the standard probe arrangement and the double-density probe arrangement. The uneven thickness of the superficial layer, which cannot be evaluated by the previous slab model, affects the distribution of measured activation in the topographic image, and this reduces the position reproducibility of near-infrared (NIR) topography with the standard probe arrangement. The overlapping measurements by the double-density probe arrangement can improve the reproducibility of the image obtained by NIR topography. PMID- 17356609 TI - Subsurface diffuse optical tomography can localize absorber and fluorescent objects but recovered image sensitivity is nonlinear with depth. AB - Subsurface tomography with diffuse light has been investigated with a noncontact approach to characterize the performance of absorption and fluorescence imaging. Using both simulations and experiments, the reconstruction of local subsurface heterogeneity is demonstrated, but the recovery of target size and fluorophore concentration is not linear when changes in depth occur, whereas the mean position of the object for experimental fluorescent and absorber targets is accurate to within 0.5 and 1.45 mm when located within the first 10 mm below the surface. Improvements in the linearity of the response with depth appear to remain challenging and may ultimately limit the approach to detection rather than characterization applications. However, increases in tissue curvature and/or the addition of prior information are expected to improve the linearity of the response. The potential for this type of imaging technique to serve as a surgical guide is highlighted. PMID- 17356610 TI - Optimal sparse solution for fluorescent diffuse optical tomography: theory and phantom experimental results. AB - We present a method to accurately localize small fluorescent objects within the tissue using fluorescent diffuse optical tomography (FDOT). The proposed method exploits the localized or sparse nature of the fluorophores in the tissue as a priori information to considerably improve the accuracy of the reconstruction of fluorophore distribution. This is accomplished by minimizing a cost function that includes the L1 norm of the fluorophore distribution vector. Experimental results for a milk-based phantom using a fiber-based cw FDOT system demonstrate the capability of this method in accurately localizing small fluorescent objects deep in the phantom. PMID- 17356612 TI - Image correction algorithm for functional three-dimensional diffuse optical tomography brain imaging. AB - We outline a computationally efficient image correction algorithm, which we have applied to diffuse optical tomography (DOT) image time series derived from a magnetic resonance imaging (MRI)-based brain model. Results show that the algorithm increases spatial resolution, decreases spatial bias, and only modestly reduces temporal accuracy for noise levels typically seen in experiment, and produces results comparable to image reconstructions that incorporate information from MRI priors. We demonstrate that this algorithm has robust performance in the presence of noise, background heterogeneity, irregular external and internal boundaries, and error in the initial guess. However, the algorithm introduces artifacts when the absorption and scattering coefficients of the reference medium are overestimated--a situation that is easily avoided in practice. The considered algorithm offers a practical approach to improving the quality of images from time-series DOT, even without the use of MRI priors. PMID- 17356611 TI - Comparison of simplified Monte Carlo simulation and diffusion approximation for the fluorescence signal from phantoms with typical mouse tissue optical properties. AB - A simplified approach is proposed to simulate the fluorescence signal from a fluorophore submerged inside a turbid medium using the Monte Carlo method. Based on the reversibility of photon propagation, the fluorescence signal can be obtained from a single Monte Carlo simulation of the excitation light. This is computationally less expensive and also allows for the direct use of well validated nonfluorescence photon migration Monte Carlo codes. Fluorescence signals from a mouse tissuelike phantom were computed using both the simplified Monte Carlo simulation and the diffusion approximation. The relative difference of signal intensity was found to be at most 30% for a fluorophore placed in the medium at various depths and horizontally midway between a source-detector pair separated by 3 mm. The difference in time characteristics of the signal is also examined. PMID- 17356613 TI - Image correction scheme applied to functional diffuse optical tomography scattering images. AB - We have extended our investigation on the use of a linear algorithm for enhancing the accuracy of diffuse optical tomography (DOT) images, to include spatial maps of the diffusion coefficient. The results show that the corrected images are markedly improved in terms of estimated size, spatial resolution, two-object resolving power, and quantitative accuracy. These image-enhancing effects are significant at expected levels of diffusion-coefficient contrast in tissue and noise levels typical of experimental DOT data. Overall, the types and magnitudes of image-enhancing effects obtained here are qualitatively similar to those seen in previous studies on mu(a) perturbations. The implications for practical implementations of DOT time-series imaging are discussed. PMID- 17356614 TI - In vivo time-resolved reflectance spectroscopy of the human forehead. AB - We present an in vivo broadband spectroscopic characterization of the human forehead. Absorption and scattering properties are measured on five healthy volunteers at five different interfiber distances, using time-resolved diffuse spectroscopy and interpreting data with a model of the diffusion equation for a homogeneous semi-infinite medium. A wavelength-tunable mode-locked laser and time correlated single-photon counting detection are employed, enabling fully spectroscopic measurements in the range of 700-1000 nm. The results show a large variation in the absorption and scattering properties of the head depending on the subject, whereas intrasubject variations, assessed at different interfiber distances, appear less relevant, particularly for what concerns the absorption coefficient. The high intersubject variability observed indicates that a unique set of optical properties for modeling the human head cannot be used correctly. To better interpret the results of the analysis of in vivo measurements, we performed a set of four-layer model Monte Carlo simulations based on different data sets for the optical properties of the human head, partially derived from the literature. The analysis indicated that, when simulated time-resolved curves are fitted with a homogeneous model for the photon migration, the retrieved absorption and reduced scattering coefficients are much closer to superficial layer values (i.e., scalp and skull) than to deeper layer ones (white and gray matter). In particular, for the shorter interfiber distances, the recovered values can be assumed as a good estimate of the optical properties of the first layer. PMID- 17356615 TI - Chemical concentration measurement in blood serum and urine samples using liquid core optical fiber Raman spectroscopy. AB - We report measurements of chemical concentrations in clinical blood serum and urine samples using liquid-core optical fiber (LCOF) Raman spectroscopy to increase the collected signal strength. Both Raman and absorption spectra were acquired in the near-infrared region using the LCOF geometry. Spectra of 71 blood serum and 61 urine samples were regressed via partial least squares against reference analyzer values. Significant correlation was found between predicted and reference concentrations for 13 chemicals. Using absorption data to normalize the LCOF enhancement made the results more accurate. The experimental geometry is well suited for high-volume and automated chemical analysis of clear biofluids. PMID- 17356616 TI - Polarization effects on scatterer sizing accuracy analyzed with frequency-domain angle-resolved low-coherence interferometry. AB - Angle-resolved low-coherence interferometry (a/LCI) enables us to make depth resolved measurements of scattered light that can be used to recover subsurface structural information such as the size of cell nuclei. Endoscopic frequency domain a/LCI (fa/LCI) acquires data by using a novel fiber probe in a fraction of a second, making it a clinically practical system. However, birefringent effects in fiber-based systems can alter the polarization state of the incident light and potentially skew the collected data. We analyze the effect the polarization state of the incident light has on scattering data collected from polystyrene microsphere tissue phantoms and in vitro cell samples and examine the subsequent accuracy of the determined sizes. It is shown that the endoscopic fa/LCI system accurately determines the size of polystyrene microspheres without the need to control the polarization of the incident beam, but that epithelial cell nuclear sizes are accurately determined only when the polarization state of the incident light is well characterized. PMID- 17356617 TI - Empirical model functions to calculate hematocrit-dependent optical properties of human blood. AB - The absorption coefficient, scattering coefficient, and effective scattering phase function of human red blood cells (RBCs) in saline solution were determined for eight different hematocrits (Hcts) between 0.84% and 42.1% in the wavelength range of 250-1100 nm using integrating sphere measurements and inverse Monte Carlo simulation. To allow for biological variability, averaged optical parameters were determined under flow conditions for ten different human blood samples. Based on this standard blood, empirical model functions are presented for the calculation of Hct-dependent optical properties for the RBCs. Changes in the optical properties when saline solution is replaced by blood plasma as the suspension medium were also investigated. PMID- 17356618 TI - Simultaneous recording of skin blood pulsations at different vascular depths by multiwavelength photoplethysmography. AB - A new technique for parallel recording of reflection photoplethysmography (PPG) signals in a broad spectral band (violet to near-infrared) has been developed, and its potential for assessment of blood microcirculation at various depths from the skin surface is discussed. PPG signals have been simultaneously detected at cw laser wavelength sets comprising 405, 532, 645, 807, and 1064 nm. Various signal baseline responses to breath holding and different shapes of the PPG pulses originated from the same heartbeat but recorded at different wavelengths have been observed, indicating a depth variety of the skin blood pulsation dynamics. PMID- 17356620 TI - High-resolution frequency-domain second-harmonic optical coherence tomography. AB - We used continuum generated in an 8.5 cm long fiber by a femtosecond Yb fiber laser to improve threefold the axial resolution of frequency domain second harmonic optical coherence tomography (SH-OCT) to 12 microm. The acquisition time was shortened by more than 2 orders of magnitude compared to the time-domain SH OCT. The system was applied to image biological tissue of fish scales, pig leg tendon, and rabbit eye sclera. Highly organized collagen fibrils can be visualized in the recorded images. Polarization dependence on the SH has been used to obtain polarization resolved images. PMID- 17356619 TI - Confocal light absorption and scattering spectroscopic microscopy. AB - We have developed a novel optical method for observing submicrometer intracellular structures in living cells, which is called confocal light absorption and scattering spectroscopic (CLASS) microscopy. It combines confocal microscopy, a well-established high-resolution microscopic technique, with light scattering spectroscopy. CLASS microscopy requires no exogenous labels and is capable of imaging and continuously monitoring individual viable cells, enabling the observation of cell and organelle functioning at scales of the order of 100 nm. PMID- 17356621 TI - Phenotyping transgenic embryonic murine hearts using optical coherence tomography. AB - We used optical coherence tomography (OCT) to characterize the morphological phenotype of embryonic murine hearts discerning hexamethylene-bis-acetamide inducible protein 1 (HEXIM1) mutants from their wild-type littermates. At E12.5 and E13.5 murine embryos were excised from the mother, the hearts were removed, and 3D OCT data sets were obtained from each heart in the litter. Next, we segmented the morphological borders to obtain cavity volumes and wall thicknesses. The mutant hearts exhibited increased ventricular chamber volume and decreased compact myocardium wall thickness when compared with their wild-type littermates. Also, the E13.5 HEXIM1 -/- embryo was distinguished by morphological asymmetry (underdeveloped left side). PMID- 17356622 TI - Correlation between optical coherence tomography images and histology of pigskin. AB - Noninvasive imaging techniques such as optical coherence tomography (OCT) are being widely used for early diagnostics of a variety of pathologies. Traditional tissue preparation for histological evaluation alters the dimensions of histological images such that differences between the dimensions of histologic and OCT images can be as great as 2.5-fold. This discrepancy complicates quantitative interpretation of OCT images. Here we used a steel ring sewn to the pigskin to avoid tissue deformation due to excision and fixation and used a surgical suture as a fixed tissue marker. With these techniques, we achieved good correlation between OCT and histological images with differences of less than 10%. The resulting method significantly enhances the diagnostic capabilities of the OCT technique. PMID- 17356623 TI - Optimization of dual-band continuum light source for ultrahigh-resolution optical coherence tomography. AB - We demonstrate a dual-band continuum light source centered at 830 and 1300 nm for optical coherence tomography (OCT) generated by pumping a photonic crystal fiber having two closely spaced zero-dispersion wavelengths with a femtosecond laser at 1059 nm. By use of polarization control, sidelobe suppression can be improved up to approximately 7.7 dB. By employing compression of the pump pulses, the generated spectrum is smooth and near-Gaussian, resulting in a point-spread function with negligible sidelobes. We demonstrate ultrahigh-resolution OCT imaging of biological tissue in vivo and in vitro using this light source and compare it with conventional-resolution OCT imaging at 1300 nm. PMID- 17356624 TI - Multiscan time-domain optical coherence tomography for retina imaging. AB - A versatile time-domain optical coherence tomography system is presented that can generate cross-sectional images by using either transverse priority or depth priority scanning. This is made possible by using a transmissive scanning delay line compatible with balance detection operating at a speed similar to that of the transverse scanner used to scan the beam across the target. In vivo images from the retina are generated and shown using the same system switched to either transverse or depth priority scanning regime, by using the scanning delay line either in slow or fast scanning modes, respectively. A comparative analysis of different scanning regimes depending on image size to fit different areas to be imaged is presented. Safety thresholds due to the different continuous irradiation time per transverse pixel in different scanning regimes are also considered. We present the maximum exposure level for a variety of scanning procedures, employing either A scanning (depth priority) or T scanning (transverse priority) when generating cross-sectional images, en face images, or collecting 3D volumes. PMID- 17356625 TI - Directional eye fixation sensor using birefringence-based foveal detection. AB - We recently developed and reported an eye fixation monitor that detects the fovea by its radial orientation of birefringent nerve fibers. The instrument used a four-quadrant photodetector and a normalized difference function to check for a best match between the detector quadrants and the arms of the bow-tie pattern of polarization states surrounding the fovea. This function had a maximum during central fixation but could not tell where the subject was looking relative to the center. We propose a linear transformation to obtain horizontal and vertical eye position coordinates from the four photodetector signals, followed by correction based on a priori calibration information. The method was verified on both a computer model and on human eyes. The major advantage of this new eye-tracking method is that it uses true information coming from the fovea, rather than reflections from other structures, to identify the direction of foveal gaze. PMID- 17356626 TI - Gaussian approximations of fluorescence microscope point-spread function models. AB - We comprehensively study the least-squares Gaussian approximations of the diffraction-limited 2D-3D paraxial-nonparaxial point-spread functions (PSFs) of the wide field fluorescence microscope (WFFM), the laser scanning confocal microscope (LSCM), and the disk scanning confocal microscope (DSCM). The PSFs are expressed using the Debye integral. Under an L(infinity) constraint imposing peak matching, optimal and near-optimal Gaussian parameters are derived for the PSFs. With an L1 constraint imposing energy conservation, an optimal Gaussian parameter is derived for the 2D paraxial WFFM PSF. We found that (1) the 2D approximations are all very accurate; (2) no accurate Gaussian approximation exists for 3D WFFM PSFs; and (3) with typical pinhole sizes, the 3D approximations are accurate for the DSCM and nearly perfect for the LSCM. All the Gaussian parameters derived in this study are in explicit analytical form, allowing their direct use in practical applications. PMID- 17356627 TI - Comparison of Hartmann analysis methods. AB - Analysis of Hartmann-Shack wavefront sensors for the eye is traditionally performed by locating and centroiding the sensor spots. These centroids provide the gradient, which is integrated to yield the ocular aberration. Fourier methods can replace the centroid stage, and Fourier integration can replace the direct integration. The two--demodulation and integration--can be combined to directly retrieve the wavefront, all in the Fourier domain. Now we applied this full Fourier analysis to circular apertures and real images. We performed a comparison between it and previous methods of convolution, interpolation, and Fourier demodulation. We also compared it with a centroid method, which yields the Zernike coefficients of the wavefront. The best performance was achieved for ocular pupils with a small boundary slope or far from the boundary and acceptable results for images missing part of the pupil. The other Fourier analysis methods had much higher tolerance to noncentrosymmetric apertures. PMID- 17356628 TI - Quantitative phase imaging of live cells using fast Fourier phase microscopy. AB - Using the decomposition of an image field in two spatial components that can be controllably shifted in phase with respect to each other, a new quantitative phase microscope has been developed. The new instrument, referred to as the fast Fourier phase microscope (f-FPM), provides a factor of 100 higher acquisition rate compared with our previously reported Fourier phase microscope. The resulting quantitative-phase images are characterized by diffraction limited transverse resolution and path-length stability better than 2 nm at acquisition rates of 10 frames/s or more. These features make the f-FPM particularly appealing for investigating the structure and dynamics of live cells over a broad range of time scales. In addition, we demonstrate the possibility of examining subcellular structures by digitally processing the amplitude and phase information provided by the instrument. Thus we developed software that can emulate phase contrast and differential interference contrast microscopy images by numerically processing FPM images. This approach adds the flexibility of digitally varying the phase shift between the two interfering beams. The images obtained appear as if they were recorded by variable phase contrast or differential interference contrast microscopes that deliver an enhanced view to the subcellular structure when compared with the typical commercial microscope. PMID- 17356629 TI - Confocal theta line-scanning microscope for imaging human tissues. AB - A confocal reflectance theta line-scanning microscope demonstrates imaging of nuclear and cellular morphology in human skin and oral mucosa in vivo. The illumination and detection are through a divided objective lens pupil, resulting in a theta-microscope configuration. A line is directly scanned in the pupil and descanned onto a linear detector array such that the theta line scanner consists of only seven main optical components. The experimentally measured lateral resolution is 1.0 microm and optical section thickness is 1.7 microm under nominal conditions at 830 nm wavelength. Through full-thickness human epidermis (i.e., in the dermis) the measured lateral resolution is 1.7 microm and the optical section thickness is 9.2 microm. The lateral resolution, sectioning, and image quality in epidermal (epithelial) tissue is comparable to that of point scanning confocal microscopy. PMID- 17356630 TI - Influence of semicrystalline order on the second-harmonic generation efficiency in the anisotropic bands of myocytes. AB - The influence of semicrystalline order on the second-harmonic generation (SHG) efficiency in the anisotropic bands of Drosophila melanogaster sarcomeres from larval and adult muscle has been investigated. Differences in the semicrystalline order were obtained by using wild-type and mutant strains containing different amounts of headless myosin. The reduction in semicrystalline order without altering the chemical composition of myofibrils was achieved by observing highly stretched sarcomeres and by inducing a loss of viability in myocytes. In all cases the reduction of semicrystalline order in anisotropic bands of myocytes resulted in a substantial decrease in SHG. Second-harmonic imaging during periodic contractions of myocytes revealed higher intensities when sarcomeres were in the relaxed state compared with the contracted state. This study demonstrates that an ordered semicrystalline arrangement of anisotropic bands plays a determining role in the efficiency of SHG in myocytes. PMID- 17356631 TI - Random access three-dimensional two-photon microscopy. AB - We propose a two-photon microscope scheme capable of real-time, three-dimensional investigation of the electric activity pattern of neural networks or signal summation rules of individual neurons in a 0.6 mm x 0.6 mm x 0.2 mm volume of the sample. The points of measurement are chosen according to a conventional scanning two-photon image, and they are addressed by separately adjustable optical fibers. This allows scanning at kilohertz repetition rates of as many as 100 data points. Submicrometer spatial resolution is maintained during the measurement similarly to conventional two-photon microscopy. PMID- 17356632 TI - Recording invertebrate nerve activation with modulated light changes. AB - Optical scattering techniques have the potential to provide noninvasive measurements of neural activity with good spatial and temporal resolution. We used the lobster nerve as a model system to investigate and record event-related optical signals with a modulated light source and heterodyne detection system. We observed changes in the transmitted birefringent light intensity, corresponding with electrophysiological measurements of the action potential. The photon delay was below the detection threshold, in part due to the small size of the nerve bundle. Our system allowed us to place an upper bound on the magnitude of the phase change of 0.01 degrees. The physiological stability of the preparation allows comprehensive characterization of biological and instrumentation noise sources for testing optical measurement systems. PMID- 17356633 TI - Long-term optical imaging of intrinsic signals in anesthetized and awake monkeys. AB - Some exciting new efforts to use intrinsic signal optical imaging methods for long-term studies in anesthetized and awake monkeys are reviewed. The development of such methodologies opens the door for studying behavioral states such as attention, motivation, memory, emotion, and other higher-order cognitive functions. Long-term imaging is also ideal for studying changes in the brain that accompany development, plasticity, and learning. Although intrinsic imaging lacks the temporal resolution offered by dyes, it is a high spatial resolution imaging method that does not require application of any external agents to the brain. The bulk of procedures described here have been developed in the monkey but can be applied to the study of surface structures in any in vivo preparation. PMID- 17356634 TI - Integrated semiconductor optical sensors for cellular and neural imaging. AB - We review integrated optical sensors for functional brain imaging, localized index-of-refraction sensing as part of a lab-on-a-chip, and in vivo continuous monitoring of tumor and cancer stem cells. We present semiconductor-based sensors and imaging systems for these applications. Measured intrinsic optical signals and tissue optics simulations indicate the need for high dynamic range and low dark-current neural sensors. Simulated and measured reflectance spectra from our guided resonance filter demonstrate the capability for index-of-refraction sensing on cellular scales, compatible with integrated biosensors. Finally, we characterized a thermally evaporated emission filter that can be used to improve sensitivity for in vivo fluorescence sensing. PMID- 17356635 TI - Oblique-incidence reflectivity difference microscope for label-free high throughput detection of biochemical reactions in a microarray format. AB - We describe a recently developed oblique-incidence reflectivity difference (OI RD) microscope, a form of polarization-modulated imaging ellipsometer, for label free-high-throughput detection of biomolecular reactions on DNA and protein microarrays. We present examples of application of this technique to end-point and real-time investigations of DNA-DNA hybridization, antibody-antigen capture, and protein-small-molecule binding reactions. Compared to a conventional imaging ellipsometer based on the polarizer-compensator-sample-analyzer scheme and under the off-null condition, a polarization-modulated OI-RD microscope is inherently more sensitive by at least 1 order of magnitude to thickness changes on a solid surface. Compared with imaging surface plasmon resonance microscopes based on reflectance change on falling or rising slopes of the surface plasmon resonance, the OI-RD microscope (1) has a comparable sensitivity, (2) is applicable to conventional microscope glass slides, and (3) easily covers a field of view as large as the entire surface of a 1 in. x 3 in. (2.54 cm x 7.62 cm) microscope slide. PMID- 17356636 TI - Liquid-crystal tunable filter spectral imaging for brain tumor demarcation. AB - Past studies have demonstrated that combined fluorescence and diffuse reflectance spectroscopy can successfully discriminate between normal, tumor core, and tumor margin tissues in the brain. To achieve efficient, real-time surgical resection guidance with optical biopsy, probe-based spectroscopy must be extended to spectral imaging to spatially demarcate the tumor margins. We describe the design and characterization of a combined fluorescence and diffuse reflectance imaging system that uses liquid-crystal tunable filter technology. Experiments were conducted to quantitatively determine the linearity, field of view, spatial and spectral resolution, and wavelength sensitivity of the imaging system. Spectral images were acquired from tissue phantoms, mouse brain in vitro, and human cortex in vivo for functional testing of the system. The spectral imaging system produces measured intensities that are linear with sample emission intensity and integration time and possesses a 1 in. (2.54 cm) field of view for a 7 in. (18 cm) object distance. The spectral resolution is linear with wavelength, and the spatial resolution is pixel-limited. The sensitivity spectra for the imaging system provide a guide for the distribution of total image integration time between wavelengths. Functional tests in vitro demonstrate the capability to spectrally discriminate between brain tissues based on exogenous fluorescence contrast or endogenous tissue composition. In vivo imaging captures adequate fluorescence and diffuse reflectance intensities within a clinically viable 2 min imaging time frame and demonstrates the importance of hemostasis to acquired signal strengths and imaging speed. PMID- 17356637 TI - Monitoring thermal-induced changes in tumor blood flow and microvessels with laser speckle contrast imaging. AB - Laser speckle contrast imaging (LSCI) was used to monitor thermal-induced changes in the blood flow and the diameter of mesenteric microvessels of normal and tumor bearing mice under 60 min treatment at different constant temperatures between 41 degrees C and 45 degrees C. The results show that the blood flow and the diameter increase at the beginning and then reach a plateau and finally start to decrease. The lower the temperature, the longer the plateau stays. A t-test indicates that there is no significant difference in plateau values of relative blood flow and relative diameter for the same group. For normal mice, the relative increases in the blood flow and the diameter are 1.26 and 1.41, respectively, while for tumor bearing mice they are 1.08 and 1.13, respectively. At higher treatment temperature or under longer heat treatment, there are decreases in the blood flow and the diameter, such changes in tumor-bearing mice are more obvious than those in normal mice, which means tumor microvessels are more sensitive to heat than normal. Moreover, thermal induced shrink of microvessel usually occurs sooner than the decrease in blood flow, and the relative change in diameter is larger than that in blood flow. Therefore we may conclude that deformation of vessel is a main factor for changing the blood perfusion of a microvessel. PMID- 17356638 TI - Strategy for photostable proximity bioassays using lanthanides. AB - We report initial findings for research aimed at creating photostable lanthanide chelate reporters for proximity assays. These reporters take advantage of the nanometer-scale distance dependence of fluorescence enhancement for molecules in the vicinity of noble metal nanoparticles and also capitalize on some unique properties of lanthanide chelates. This approach promises to lead to proximity assays that do not suffer from photobleaching and offer very high on/off enhancement ratios. Results for lanthanide chelates on silver island films and in colloidal suspensions are reported. Enhancement factors range from 1 to 2 orders of magnitude, with larger enhancements for strongly quenched lanthanides. PMID- 17356639 TI - Photonic explorers based on multifunctional nanoplatforms for biosensing and photodynamic therapy. AB - Nanoparticle-based photonic explorers have been developed for intracellular sensing and photodynamic therapy (PDT). The design employs nanoparticles made of various matrices as multifunctional nanoplatforms, loading active components by encapsulation or covalent attachment. The nanoplatform for biosensing has been successfully applied to intracellular measurements of important ionic and molecular species. The nanoplatform for PDT has shown high therapeutic efficacy in a rat 9L gliosarcoma model. Specifically, a multifunctional nanoplatform that encompasses magnetic resonance imaging (MRI) and PDT agents inside, as well as targeting ligands on the surface, has been developed and applied in vivo, resulting in much improved MRI contrast enhancement and PDT efficacy. PMID- 17356641 TI - Resonant Zener tunneling in two-dimensional periodic photonic lattices. AB - We study Zener tunneling in two-dimensional photonic lattices and derive, for the case of hexagonal symmetry, the generalized Landau-Zener-Majorana model describing resonant interaction between high-symmetry points of the photonic spectral bands. We demonstrate that this effect can be employed for the generation of Floquet-Bloch modes and verify the model by direct numerical simulations of the tunneling effect. PMID- 17356640 TI - Analysis of total uncertainty in spectral peak measurements for plasmonic nanoparticle-based biosensors. AB - One goal of recent research on plasmonic nanoparticle-based sensors is maximizing nanoparticle sensitivity or shift of resonance peak wavelength per refractive index change. Equally important is a measurement system's peak location uncertainty or shift resolution. We provide systematic analyses and discuss optimization of factors that determine peak location uncertainty, reporting values as low as 0.3 nm for the presented scheme. This type of analysis is important, in part, because it provides a means of evaluating detection thresholds for biosensor applications such as analyte binding. We estimate thresholds of 310 streptavidin molecules for the presented scheme and 20 molecules with system improvements. PMID- 17356642 TI - Wavelength-independent all-fiber mode converters. AB - We have used two different photonic crystal fiber (PCF) techniques to make all fiber mode converters. An LP(01) to LP(11) mode converter was made by the ferrule technique on a drawing tower, and an LP(01) to LP(02) mode converter was made by controlled hole inflation of an existing PCF on a tapering rig. Both devices rely on adiabatic propagation rather than resonant coupling; so high extinction was achieved across a wide wavelength range. PMID- 17356643 TI - Theory of parabolic pulse generation in tapered fiber. AB - We examine similarities and differences between high-power parabolic pulse generation in an active medium and in tapered fiber with decreasing normal dispersion. Using a realistic tapered fiber design, we demonstrate the possibility of parabolic pulse generation without an external pump and determine the limitations of this approach. PMID- 17356644 TI - Single-mode microstructured optical fiber for the middle infrared. AB - Microstructured crystalline optical fiber from silver halides is described. Both experimental and theoretical evidences are presented to establish that the fiber is effectively single mode at wavelength 10.6 micro m with numerical aperture NA=0.16 and optical losses of approximately 2 dB/m. Crystalline microstructured optical fibers offer key advantages over step-index optical fibers from silver halide crystals. The wide transmission range of wavelengths 2-20 micro m provides great potential for applications in spectroscopy and for the development of a range of new crystalline-based nonlinear optical fibers. PMID- 17356645 TI - High-efficiency single-mode Raman generation in a liquid-filled photonic bandgap fiber. AB - Single-spatial-mode Raman generation in an ethanol-filled photonic bandgap fiber is demonstrated. Due to the limited bandwidth of the fiber, the generation is limited to the first Stokes order only, allowing high generated power without any visible decrease of the conversion efficiency. The realization of these two key properties opens the way to the realization of optimized compact nonlinear wavelength converters that will accommodate a large variety of usable liquids. PMID- 17356646 TI - Demonstration of soliton self-frequency shift below 1300 nm in higher-order mode, solid silica-based fiber. AB - We demonstrate soliton self-frequency shift of more than 12% of the optical frequency in a higher-order mode solid, silica-based fiber below 1300nm. This new class of fiber shows great promise for supporting Raman-shifted solitons below 1300nm in intermediate energy regimes of 1 to 10nJ that cannot be reached by index-guided photonic crystal fibers or air-core photonic bandgap fibers. By changing the input pulse energy of 200fs pulses from 1.36 to 1.63nJ we observe Raman-shifted solitons between 1064 and 1200nm with up to 57% power conversion efficiency and compressed output pulse widths less than 50fs. Furthermore, due to the dispersion characteristics of the HOM fiber, we observe redshifted Cerenkov radiation in the normal dispersion regime for appropriately energetic input pulses. PMID- 17356647 TI - On the possibility of observing bound soliton pairs in a wave-breaking-free mode locked fiber laser. AB - On the basis of numerical simulations, we explain the formation of the stable bound soliton pairs that were experimentally reported in a high-power mode-locked ytterbium fiber laser [Opt. Express 14, 6075 (2006)], in a regime where wave breaking-free operation is expected. A fully vectorial model allows one to rigorously reproduce the nonmonotonic nature for the nonlinear polarization effect that generally limits the power scalability of a single-pulse self-similar regime. Simulations show that a self-similar regime is not fully obtained, although positive linear chirps and parabolic spectra are always reported. As a consequence, nonvanishing pulse tails allow distant stable binding of highly chirped pulses. PMID- 17356648 TI - Compensation of third-order dispersion using time reversal in optical transmission systems. AB - It is shown that the third-order dispersion of an optical fiber can be compensated for using a time-reversal system that can be implemented with periodic time lenses. PMID- 17356649 TI - 522 W average power, spectrally beam-combined fiber laser with near-diffraction limited beam quality. AB - We report a three-channel, spectrally beam-combined (SBC), 1 mum fiber laser that produces 522 W of average power with near-diffraction-limited (M2 ~ 1.2) beam quality. The laser features a SBC power combining efficiency of 93%, versatile master-oscillator, power-amplifier fiber channels with up to 260 W of narrow band, polarized, and near-diffraction-limited output that is tunable over nearly the entire 1 micro m Yb(3+) gain bandwidth, and excellent prospects for significant power scaling. To our knowledge, these results represent the highest beam quality and average power achieved to date for a beam-combined fiber laser system. PMID- 17356650 TI - All-optical phase and amplitude regeneration of return-to-zero differential phase shift keying data. AB - We report a novel implementation of an all-optical rephasing, reshaping, and reamplification differential phase shift keying (DPSK) regenerator. The rephasing is based on converting phase noise into amplitude noise by using an interferometric configuration and then eliminating the amplitude noise by using a semiconductor optical amplifier (SOA). The reshaping is performed using gain competition and gain compression in a saturated SOA. The scheme was tested using 10Gbit/s, 2(23)-1 pseudorandom bit sequence return-to-zero DPSK data. The measurement shows removal of the degraded data error floor with a 6 order-of magnitude improvement in bit-error rate. The measured negative power penalty is about 4dB. Mathematical analysis shows a reduction in DPSK phase-noise power by half. PMID- 17356651 TI - Efficient operation of diode-pumped single-frequency thulium-doped fiber lasers near 2 micro m. AB - Efficient operation of diode-pumped single-frequency fiber lasers at wavelengths from 1740 to 2017 nm has been demonstrated by using a very short piece of newly developed single-mode active fiber, i.e., heavily thulium-doped germanate glass fiber. At 1893 nm, the single-frequency fiber laser has a pump threshold of 30 mW, a slope efficiency of 35%, and maximum output power of 50 mW with respect to the launched power of single-mode pump diodes at 805 nm. To the best of our knowledge, this is the highest lasing efficiency achieved in single-frequency fiber lasers operating near 2 micro m. Frequency noise of the single-frequency fiber laser at 1893 nm has been characterized and compared with that of single frequency fiber lasers at 1 and 1.55 micro m. PMID- 17356652 TI - Fundamental-mode operation in polarization-maintaining ytterbium-doped fiber with an effective area of 1400 micro m2. AB - We report, for the first time to our knowledge, fundamental-mode operation in polarization-maintaining ytterbium-doped fiber with an effective area of approximately 1400 micro m(2) and birefringence of 2.1 x 10(-4). The measured critical bending radius, R(c), defined as the radius at which the loss is equal to 3 dB for 1 m of fiber, is approximately 4 cm. Lasing with slope efficiency exceeding 60% and M(2) of 1.2 has also been demonstrated. PMID- 17356653 TI - High-speed, high-resolution optical coherence tomography retinal imaging with a frequency-swept laser at 850 nm. AB - High-speed, high-resolution optical coherence tomography (OCT) imaging of the human retina is demonstrated using a frequency-swept laser at 850 nm. A compact external cavity semiconductor laser design, optimized for swept-source ophthalmic OCT, is described. The laser enables an effective 16 kHz sweep rate with >10 mm coherence length and a tuning range of approximately 35 nm full width at half maximum, yielding an axial resolution of <7 micro m in tissue. PMID- 17356654 TI - Wave optical analysis of integral method for three-dimensional images. AB - We analyze by wave optics an integral method that produces three-dimensional (3D) images. The point light source is given at the pickup stage, and the light wave passing through each elemental lens is obtained at the display stage. The amplitude distributions of the waves from each elemental image are the same around a specific point where a 3D image is formed. Since the light waves approaching the image plane from different elemental lenses are incoherent, the synthesized value is the sum of the squared amplitudes of the waves. Therefore the modulation transfer function of this integral method is given by that of a single elemental lens. PMID- 17356655 TI - Quasi-common-path laser feedback interferometry based on frequency shifting and multiplexing. AB - We present a quasi-common-path laser feedback interferometer based on frequency shifting and multiplexing. The interferometer uses two acousto-optic modulators to shift the frequency of the target-generated feedback light by 2 Omega. A properly aligned mirror is inserted into the feedback path to generate a feedback light frequency shifted by Omega. Phase variations of the two quasi-common-path feedback light beams are simultaneously measured through heterodyne demodulation with two different reference signals. Their subtraction accurately reflects the target displacement. Under typical room conditions, the system's short-period resolution is better than 2 nm, and its 3 min displacement accuracy is 8 nm. PMID- 17356656 TI - Coherent combining of the output of two semiconductor lasers using optical phase lock loops. AB - We have experimentally demonstrated current-injection optical phase-lock loops (OPLLs) based on commercial single-section semiconductor distributed-feedback (DFB) lasers. Using two parallel OPLLs, we have obtained 87% efficient coherent power combining of the two DFB lasers. The rms differential phase error between the two lasers is about 30 degrees . PMID- 17356657 TI - Liquid-crystal-based tunable high-Q directional random laser from a planar random microcavity. AB - Temperature-tunable directional laser emission from a dye-doped liquid-crystal based planar random cavity laser is presented. The optically pumped nematic liquid crystal infiltrated planar random microcavity produces an ultranarrow linewidth (0.03 nm, corresponding to Q>20,000), highly directional (1.4 degrees divergence angle) laser emission. By increasing the temperature from 27 degrees C to 34 degrees C, the wavelength of an emitted polarized laser can be tuned between 605.8 and 608.5 (ordinary light) and 631.3 and 624.9 nm (extraordinary light). A simulation result from the transfer matrix method that matches the experimental results well is also presented. PMID- 17356658 TI - Mimicking optical activity for generating radially polarized light. AB - We propose a new scheme for generating radially polarized light by mimicking optical activity using linear birefringence. It involves a birefringent spirally varying retarder sandwiched between two orthogonally oriented quarter-wave plates. Using Poincare sphere representation, we show that the polarization transformation of such a scheme is equivalent to that of a spirally varying optical activity and is capable of generating radially polarized light. We demonstrate the proof-of-concept using y-cut crystalline quartz. PMID- 17356659 TI - Polymer waveguides from alicyclic methacrylate copolymer fabricated by deep-UV exposure. AB - We have investigated the fabrication of waveguides from alicyclic methacrylate copolymer based on refractive-index modification by deep-UV exposure. By optimizing the UV-exposure process, we were able to obtain single-mode waveguides with a propagation loss of 0.8 dB/cm at 1550 nm, which is due only to material losses in this wavelength range. The loss obtained here is comparable with that of poly(methyl methacrylate) (PMMA) waveguides fabricated by deep-UV exposure. The fabricated waveguide is also single mode at 808 nm, and its propagation loss is 0.6 dB/cm. This alicyclic methacrylate copolymer is a promising material for the fabrication of polymer waveguides by use of deep-UV exposure. PMID- 17356660 TI - Free-space fluorescence molecular tomography utilizing 360 degrees geometry projections. AB - Fluorescence tomography of diffuse media can yield optimal three-dimensional imaging when multiple projections over 360 degrees geometries are captured, compared with limited projection angle systems such as implementations in the slab geometry. We demonstrate how it is possible to perform noncontact, 360 degrees projection fluorescence tomography of mice using CCD-camera-based detection in free space, i.e., in the absence of matching fluids. This approach achieves high spatial sampling of photons propagating through tissue and yields a superior information content data set compared with fiber-based 360 degrees implementations. Reconstruction feasibility using 36 projections in 10 degrees steps is demonstrated in mice. PMID- 17356661 TI - Needle-based refractive index measurement using low-coherence interferometry. AB - We present a novel needle-based device for the measurement of refractive index and scattering using low-coherence interferometry. Coupled to the sample arm of an optical coherence tomography system, the device detects the scattering response of, and optical path length through, a sample residing in a fixed-width channel. We report use of the device to make near-infrared measurements of tissues and materials with known optical properties. The device could be used to exploit the refractive index variations of tissue for medical and biological diagnostics accessible by needle insertion. PMID- 17356662 TI - Phase retrieval in low-coherence interferometric microscopy. AB - We present compensating methods that address inherent errors in quantitative phase reporting for low-coherence interferometric techniques. A brief theoretical treatment of the problem and experimental validation using spectral domain phase microscopy demonstrate mitigation of the degrading effects of phase leakage on accurate measurement of optical path length in the vicinity of closely spaced reflectors. This result has direct implications for phase-sensitive interferometry techniques, such as Doppler imaging, as well as amplitude-based quantitative reporting. Corrected phase retrieval is demonstrated for conversion of interferometric phase to optical path length in cell surface deflections of beating cardiomyocytes. PMID- 17356663 TI - Soliton fission and supercontinuum generation in silicon waveguides. AB - We show through numerical simulations that silicon waveguides can be used to create a supercontinuum extending over 400 nm by launching femtosecond pulses as higher-order solitons. The physical process behind continuum generation is related to soliton fission, self-phase modulation, and generation of Cherenkov radiation. In contrast with optical fibers, stimulated Raman scattering plays little role. As low-energy (approximately 1 pJ) pulses and short waveguides (<1 cm) are sufficient for continuum generation, the proposed scheme should prove useful for practical applications. PMID- 17356664 TI - Vector soliton fission by reflection at nonlinear interfaces. AB - We address the reflection of vector solitons, comprising several components that exhibit multiple field oscillations, at the interface between two nonlinear media. We reveal that reflection causes fission of the input signal into sets of solitons propagating at different angles. We find that the maximum number of solitons that arises upon fission is given by the number of field oscillations in the highest-order input vector soliton. PMID- 17356665 TI - Observation of nonlinear self-trapping in triangular photonic lattices. AB - We experimentally study light self-trapping in triangular photonic lattices induced optically in nonlinear photorefractive crystals. We observe the formation of two-dimensional discrete and gap spatial solitons originating from the first and second bands of the linear transmission spectrum. PMID- 17356666 TI - High-power, continuous-wave, singly resonant optical parametric oscillator based on MgO:sPPLT. AB - We report a high-power, widely tunable, cw singly resonant optical parametric oscillator (OPO) based on MgO:sPPLT. The OPO is pumped in the green by a cw diode pumped Nd:YVO(4) laser at 532 nm and can provide continuously tunable output across 848-1430 nm. Using a 30 mm crystal and double-pass pumping, an oscillation threshold of 2.88 W has been obtained, and single-pass idler powers in excess of 1.51 W have been generated over 1104-1430 nm for 6W of pump power at an extraction efficiency of 25.2% and photon conversion efficiency of 56.7%. PMID- 17356667 TI - Simultaneous bidirectional message transmission in a chaos-based communication scheme. AB - We introduce a chaos-based communication scheme allowing for bidirectional exchange of information. Coupling [corrected] two semiconductor lasers through a partially transparent optical mirror, placed in the pathway connecting the lasers [corrected] delay dynamics is induced in both lasers. We numerically demonstrate that this dynamics can be identically synchronized, and moreover, information introduced on both ends of the link can be simultaneously transmitted. This scheme allows one to negotiate a key through a public channel. PMID- 17356668 TI - Intraocular lens to correct corneal coma. AB - We present a new methodology to obtain, to the best of our knowledge, the first intraocular lens (IOL) designed to balance the coma induced by the cornea due to the global ocular tilt. This lens is designed to mimic the situation naturally occurring in the normal healthy eye. The new proposed IOL provides an improved optical quality for all lens powers. PMID- 17356669 TI - Observation of nanojet-induced modes with small propagation losses in chains of coupled spherical cavities. AB - Nanojet-induced modes (NIMs) and their attenuation properties are studied in linear chains consisting of tens of touching polystyrene microspheres with sizes in the 2-10 micro m range. To couple light to NIMs we used locally excited sources of light formed by several dye-doped fluorescent microspheres from the same chain of cavities. We directly observed the formation and propagation of NIMs by means of the scattering imaging technique. By measuring attenuation at long distances from the source, we demonstrate propagation losses for NIMs as small as 0.5 dB per sphere. PMID- 17356670 TI - Coherent electrically excited organic semiconductors: visibility of interferograms and emission linewidth. AB - Recently, a tandem organic light-emitting diode structure, excited electrically in the pulsed domain and confined within a double interferometric configuration, was observed to emit a low-divergence beam (approximately 1.1 times the diffraction limit) with a near-Gaussian spatial distribution. The emission originates from the laser dye Coumarin 545 T used as dopant. It has since been determined that the visibility of the interferograms, from the spatially coherent emission, is V approximately 0.90. This result is compared with the visibility obtained from a known narrow linewidth laser source (V approximately 0.95) and with various published values from the relevant literature. The significance of this result is discussed in addition to an interferometric estimate of the emission linewidth that yields Delta lambda approximately 11 nm. The present interferometric analysis indicates that the spectral component of the spatially coherent radiation is comparable with the spectral characteristics of well-known broadband dye lasers. PMID- 17356671 TI - Plasmon-assisted transparency in metal-dielectric microspheres. AB - We present a theoretical analysis of light scattering from a layered metal dielectric microsphere. The system consists of two spherical resonators coupled through concentric embedding. Solving for the modes of this system, we find that near an avoided crossing the scattering cross section is dramatically suppressed, exhibiting a tunable optical transparency. Similar to electromagnetically induced transparency, this phenomenon is associated with a large group delay, which in our system is manifest as flat azimuthal dispersion. PMID- 17356672 TI - Optimal filters for photon cloning with an optical amplifier. AB - We study the performance of a practical quantum cloning scheme consisting of a continuously pumped broadband optical amplifier followed by optimal spectral and temporal filters for spontaneous emission suppression. Our simulation results demonstrate that the fidelity of this system is no better than a random cloning machine when the average input photon number is below one, but asymptotically approaches the quantum limit of an optimal quantum cloning machine as the input photon number increases. We also show that this system has a better fidelity than cloning based on state estimation, though for a large number of clones both cloning methods asymptotically approach the quantum limit. PMID- 17356673 TI - Fourier transform emission lifetime spectrometer. AB - We report a rapid and low cost Fourier transform spectrometer that uses a path length modulated Michelson interferometer to simultaneously measure excitation spectra and excitation wavelength-dependent emission lifetimes. Excitation spectra and lifetimes of excited tris(2,2'-bipyridyl) ruthenium(II) measured using this technique corresponded to values known in the literature. Excitation dependent lifetimes of porous silicon measured with this technique suggest the influence of quantum confinement effects. This method may be useful for measuring mixtures of emitting species with closely spaced lifetimes as well as studying excitation wavelength-dependent emission phenomena. PMID- 17356674 TI - Sensing and compensation of femtosecond waveform distortion induced by all-order polarization mode dispersion at selected polarization states. AB - We demonstrate full characterization of femtosecond pulse distortion induced by all-order polarization mode dispersion (PMD) at selected polarization states via second-harmonic generation (SHG) frequency-resolved optical gating (FROG) measurements at an average power of under 28 nW. By applying the inverse of the measured spectral phase via a programmable pulse shaper, we compress the distorted pulses from more than 3 ps to nearly bandwidth-limited durations of less than 500 fs. Our results show that SHG FROG measurements performed by using fiber-pigtailed aperiodically poled lithium niobate waveguides can serve as a robust and sensitive tool for characterization of PMD-induced spectral phase. PMID- 17356675 TI - Ultrafast x-ray pulses emitted from a liquid mercury laser target. AB - We report the generation of ultrashort, hard-x-ray pulses from a liquid mercury target irradiated by 5 kHz laser pulses. The new x-ray source is designed for time-resolved x-ray absorption spectroscopy as well as imaging applications. This marks the first laser-driven plasma x-ray source that continuously recycles the target material, facilitating maintenance-free operation. Theoretical calculations show mercury targets emit shorter x-ray pulses than targets of lighter elements under identical illumination and x-ray detection conditions. PMID- 17356676 TI - Passively mode-locked lasers with 17.2-GHz fundamental-mode repetition rate pulsed by carbon nanotubes. AB - 17.2 GHz, the highest fundamental-mode repetition rate to our knowledge, of a carbon nanotube-based passively mode-locked laser is realized at 1570 nm by employing purified single-walled carbon nanotubes as saturable absorbers. The ultrashort linear laser cavity configured with a approximately 9 mm length is designed and demonstrated with our extremely miniaturized nanotube mode locker and a mirror-coated semiconductor optical amplifier as gain medium. The demonstrated pulsed laser has the inferred temporal pulse width of 14 ps and a 3 dB spectral bandwidth of 0.73 nm. PMID- 17356677 TI - Generation of radially polarized terahertz pulses via velocity-mismatched optical rectification. AB - We demonstrate the generation of radially polarized terahertz pulses via optical rectification in a Cherenkov geometry exploiting velocity mismatch, contrary to the traditional approach for generating linearly polarized terahertz beams. A compact system is implemented using 001-cut ZnTe pumped by an ultrafast Yb-doped fiber amplifier. PMID- 17356678 TI - Transient phase masks in high-harmonic generation. AB - We present a method for controlling the spatial properties of high-harmonic beams with high efficiency. The high nonlinearity of harmonic generation allows weak control beams to induce a phase mask for the extreme UV light as it is formed. We fabricate a phase grating and demonstrate efficient diffraction in the far field. Diffractive elements formed in this way are transient. Since they are induced by the subcycle interaction of the medium with the fundamental and control fields, they can be extended to the attosecond time scale. PMID- 17356679 TI - Preferential Segregation in Triplo-IV Females of Drosophila Melanogaster. PMID- 17356680 TI - The Differentiation of Eye Pigments in Drosophila as Studied by Transplantation. PMID- 17356681 TI - THE SYNTAX-DISCOURSE DIVIDE: PROCESSING ELLIPSIS. AB - VP-ellipsis and sluicing are forms of ellipsis that can cross a sentence boundary. We present a series of comprehension studies on these forms of ellipsis to elucidate their processing and the relation of syntactic and discourse processing. One set of studies examines the hypothesis that the representation of elided material is syntactically structured. We present evidence supporting the hypothesis and tentatively attribute the effects to sharing of the structure of the antecedent constituent, with structure building or substitution of a variable for a constituent permitted if it is licensed by the syntactic principles of the language. Another set of studies tests the hypothesis that a new utterance is preferentially related to the main assertion of the preceding utterance, which is typically a constituent high in the syntactic tree. The results suggest that discourse processing differs from syntactic processing, where the most accessible material is recent material found low in the syntactic tree. A final set of studies examines the interplay of the syntactic processor, which may not violate "islands," and the discourse processor, which may, in the processing of ellipsis sentences involving islands. A novel explanation is offered for the observation (Ross 1967) that sluicing out of relative-clause islands is grammatical except when sprouting is required. PMID- 17356682 TI - Amnestying Superiority Violations: Processing Multiple Questions. AB - Two experiments investigated the acceptability of multiple questions. As expected, sentences violating the Superiority Condition were accepted less often than sentences obeying it. The status of the Superiority violations was not improved by the addition of a third wh, regardless of whether the third wh was an adjunct or an argument, though it was improved by the addition of a second question (e.g., and when). Further, in a small pilot study directly comparing a sentence with adjacent final wh-phrases that may induce a stress clash (I'd like to know who hid it where when) with a sentence violating Superiority but avoiding the final adjacent wh-phrases (I'd like to know where who hid it when), half the participants indicated that the Superiority violation sentence sounded better. This suggests that the status of some additional-wh sentences may appear to improve simply because the comparison sentence with adjacent final wh-phrases is degraded. Overall, the results of the studies suggest that there is no need to complicate syntactic theory to account for the additional-wh effect, because there is no general additional-wh effect. PMID- 17356683 TI - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress." Central role of technology in the treatment and prevention of Alzheimer's disease. PMID- 17356684 TI - Astroglial heterogeneity closely reflects the neuronal-defined anatomy of the adult murine CNS. AB - Astroglia comprise an extremely morphologically diverse cell type that have crucial roles in neural development and function. Nonetheless, distinct regions of the CNS have traditionally been defined by the phenotypic characteristics and connectivity of neuros. In a complementary fashion, we present evidence that discrete regions of the adult CNS can be delineated based solely on the morphology, density and proliferation rates of astroglia. We used transgenic hGFAP-GFP mice in which robust expression of GFP in adult astroglia enables detailed morphological characterization of this diversely heterogeneous cell population with 3D confocal microscopy. By using three complementary methods for labeling adult astroglia (hGFAP-GFP expression, and GFAP and S100beta immunostaining), we find that there is a remarkably diverse, regionally stereotypical array of astroglial morphology throughout the CNS, and that discrete anatomical regions can be defined solely on the morphology of astroglia within that region. Second, we find that the density of astroglia varies dramatically across the CNS, and that astroglial density effectively delineates even the sub-regions of complex structures, such as the thalamus. We also find that regional astroglial density varies depending on how astroglia are labeled. To quantify and illustrate these broad differences in astroglial density, we generated an anatomical density atlas of the CNS. Third, the proliferation rate, or mitotic index, of astroglia in the adult CNS also effectively defines anatomical regions. These differences are present regardless of the astroglial labeling method used. To supplement our atlas of astroglial density we generated an atlas of proliferation density for the adult CNS. Together, these studies demonstrate that the morphology, density and proliferation rate of astroglia can independently define the discrete cytoarchitecture of the adult mammalian CNS, and support the concept that regional astroglial heterogeneity reflects important molecular and functional differences between distinct classes of astroglia, much like the long-accepted heterogeneity of neuronal populations. PMID- 17356685 TI - Nutritional Alterations in Drug Abusers With and Without HIV. AB - Many studies have found that drug abusers have nutritional deficits, including weight deficits. The most plausible explanation for these deficits is dietary insufficiency. However, studies using objective measures of the dietary intake of drug abusers have failed to provide evidence of dietary insufficiency. Other mechanisms have rarely been examined. This article reviews the published literature on the nutritional status of drug abusers with and without HIV, with emphasis on dietary energy and macronutrient intake. PMID- 17356687 TI - HAPPY PEOPLE BECOME HAPPIER THROUGH KINDNESS: A COUNTING KINDNESSES INTERVENTION. AB - We examined the relationship between the character strength of kindness and subjective happiness (Study 1), and the effects of a counting kindnesses intervention on subjective happiness (Study 2). In Study 1, participants were 175 Japanese undergraduate students and in Study 2, participants were 119 Japanese women (71 in the intervention group and 48 in the control group). Results showed that: (a) Happy people scored higher on their motivation to perform, and their recognition and enactment of kind behaviors. (b) Happy people have more happy memories in daily life in terms of both quantity and quality. (c) Subjective happiness was increased simply by counting one's own acts of kindness for one week. (d) Happy people became more kind and grateful through the counting kindnesses intervention. Discussion centers on the importance of kindness in producing subjective happiness. PMID- 17356686 TI - Imitating expressions: emotion-specific neural substrates in facial mimicry. AB - Intentionally adopting a discrete emotional facial expression can modulate the subjective feelings corresponding to that emotion; however, the underlying neural mechanism is poorly understood. We therefore used functional brain imaging (functional magnetic resonance imaging) to examine brain activity during intentional mimicry of emotional and non-emotional facial expressions and relate regional responses to the magnitude of expression-induced facial movement. Eighteen healthy subjects were scanned while imitating video clips depicting three emotional (sad, angry, happy), and two 'ingestive' (chewing and licking) facial expressions. Simultaneously, facial movement was monitored from displacement of fiducial markers (highly reflective dots) on each subject's face. Imitating emotional expressions enhanced activity within right inferior prefrontal cortex. This pattern was absent during passive viewing conditions. Moreover, the magnitude of facial movement during emotion-imitation predicted responses within right insula and motor/premotor cortices. Enhanced activity in ventromedial prefrontal cortex and frontal pole was observed during imitation of anger, in ventromedial prefrontal and rostral anterior cingulate during imitation of sadness and in striatal, amygdala and occipitotemporal during imitation of happiness. Our findings suggest a central role for right inferior frontal gyrus in the intentional imitation of emotional expressions. Further, by entering metrics for facial muscular change into analysis of brain imaging data, we highlight shared and discrete neural substrates supporting affective, action and social consequences of somatomotor emotional expression. PMID- 17356688 TI - Phenobarbital for childhood epilepsy: systematic review. AB - INTRODUCTION: Against a background of concern about the safety of new pharmaceutical products, there has been renewed interest in one of the oldest antiepileptic drugs (AEDs), phenobarbital. Although still in widespread use in developing countries, its popularity has slipped in Western countries over the past century, partly because of controversy about its adverse effect profile. This critical review examines the evidence supporting its effectiveness and its associated behavioural adverse effects for febrile convulsions and childhood epilepsy. METHODS: Relevant randomised controlled trials (RCTs) of phenobarbital vs other antiepileptic drugs or placebo between 1970-2005 were identified through a comprehensive manual and computer database search of the world biomedical literature. Eleven RCTs of febrile convulsions and nine RCTs of childhood epilepsy were systematically reviewed against a conventional set of quality criteria. RESULTS: With a few exceptions, the overall quality of clinical trial methodology, especially in the early studies conducted in the 1970s and 1980s, was poor. There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED, yet no evidence for absolute efficacy. No convincing evidence exists for an excess of behavioural adverse effects, over other AEDs, attributable to phenobarbital. Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs. This is in contrast to the excess of such adverse effects reported in studies open to observer bias. However, the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern. Future areas of clinical and genetic epidemiological research are outlined. PMID- 17356689 TI - Molecular diversity of legume root-nodule bacteria in Kakadu National Park, Northern Territory, Australia. AB - BACKGROUND: Symbiotic relationships between leguminous plants (family Fabaceae) and nodule-forming bacteria in Australia native ecosystems remain poorly characterized despite their importance. Most studies have focused on temperate parts of the country, where the use of molecular approaches have already revealed the presence of Bradyrhizobium, Ensifer (formerly Sinorhizobium), Mesorhizobium and Rhizobium genera of legume root-nodule bacteria. We here provide the first molecular characterization of nodulating bacteria from tropical Australia. METHODOLOGY/PRINCIPAL FINDINGS: 45 nodule-forming bacterial strains, isolated from eight native legume hosts at eight locations in Kakadu National Park, Northern Territory, Australia, were examined for their genetic diversity and phylogenetic position. Using SSU rDNA PCR-RFLPs and phylogenetic analyses, our survey identified nine genospecies, two of which, Bradyrhizobium genospp. B and P, had been previously identified in south-eastern Australia and one, Mesorhizobium genospecies AA, in southern France. Three of the five newly characterized Bradyrhizobium genospecies were more closely related to B. japonicum USDA110, whereas the other two belonged to the B. elkanii group. All five were each more closely related to strains sampled in various tropical areas outside Australia than to strains known to occur in Australia. We also characterized an entirely novel nodule-forming lineage, phylogenetically distant from any previously described rhizobial and non-rhizobial legume-nodulating lineage within the Rhizobiales. CONCLUSIONS/SIGNIFICANCE: Overall, the present results support the hypothesis of tropical areas being centres of biodiversity and diversification for legume root-nodule bacteria and confirm the widespread occurrence of Bradyrhizobium genosp. B in continental Australia. PMID- 17356690 TI - Cytosolic 5'-triphosphate ended viral leader transcript of measles virus as activator of the RIG I-mediated interferon response. AB - BACKGROUND: Double stranded RNA (dsRNA) is widely accepted as an RNA motif recognized as a danger signal by the cellular sentries. However, the biology of non-segmented negative strand RNA viruses, or Mononegavirales, is hardly compatible with the production of such dsRNA. METHODOLOGY AND PRINCIPAL FINDINGS: During measles virus infection, the IFN-beta gene transcription was found to be paralleled by the virus transcription, but not by the virus replication. Since the expression of every individual viral mRNA failed to activate the IFN-beta gene, we postulated the involvement of the leader RNA, which is a small not capped and not polyadenylated RNA firstly transcribed by Mononegavirales. The measles virus leader RNA, synthesized both in vitro and in vivo, was efficient in inducing the IFN-beta expression, provided that it was delivered into the cytosol as a 5'-trisphosphate ended RNA. The use of a human cell line expressing a debilitated RIG-I molecule, together with overexpression studies of wild type RIG I, showed that the IFN-beta induction by virus infection or by leader RNA required RIG-I to be functional. RIG-I binds to leader RNA independently from being 5-trisphosphate ended; while a point mutant, Q299A, predicted to establish contacts with the RNA, fails to bind to leader RNA. Since the 5'-triphosphate is required for optimal RIG-I activation but not for leader RNA binding, our data support that RIG-I is activated upon recognition of the 5'-triphosphate RNA end. CONCLUSIONS/SIGNIFICANCE: RIG-I is proposed to recognize Mononegavirales transcription, which occurs in the cytosol, while scanning cytosolic RNAs, and to trigger an IFN response when encountering a free 5'-triphosphate RNA resulting from a mislocated transcription activity, which is therefore considered as the hallmark of a foreign invader. PMID- 17356691 TI - Factors associated with adherence to anti-hypertensive treatment in Pakistan. AB - OBJECTIVES: Poor adherence is one of the biggest obstacles in therapeutic control of high blood pressure. The objectives of this study were (i) to measure adherence to antihypertensive therapy in a representative sample of the hypertensive Pakistani population and (ii) to investigate the factors associated with adherence in the studied population. METHODS AND RESULTS: A cross-sectional study was conducted on a simple random sample of 460 patients at the Aga Khan University Hospital (AKUH) and National Institute of Cardiovascular Diseases, Karachi, from September 2005-May 2006. Adherence was assessed using the Morisky Medication Adherence Scale (MMAS), with scores ranging from 0 (non-adherent) to 4 (adherent). In addition to MMAS, patient self-reports about the number of pills taken over a prescribed period were used to estimate adherence as a percentage. AKU Anxiety and Depression Scale (AKU-ADS) was incorporated to find any association between depression and adherence. At a cut-off value of 80%, 77% of the cases were adherent. Upon univariate analyses, increasing age, better awareness and increasing number of pills prescribed significantly improved adherence, while depression showed no association. Significant associations, upon multivariate analyses, included number of drugs that a patient was taking (P<0.02) and whether he/she was taking medication regularly or only for symptomatic relief (P<0.00001). CONCLUSIONS: Similar to what has been reported worldwide, younger age, poor awareness, and symptomatic treatment adversely affected adherence to antihypertensive medication in our population. In contrast, monotherapy reduced adherence, whereas psychosocial factors such as depression showed no association. These findings may be used to identify the subset of population at risk of low adherence who should be targeted for interventions to achieve better blood pressure control and hence prevent complications. PMID- 17356692 TI - Transient receptor potential ion channels control thermoregulatory behaviour in reptiles. AB - Biological functions are governed by thermodynamics, and animals regulate their body temperature to optimise cellular performance and to avoid harmful extremes. The capacity to sense environmental and internal temperatures is a prerequisite for the evolution of thermoregulation. However, the mechanisms that enable ectothermic vertebrates to sense heat remain unknown. The recently discovered thermal characteristics of transient receptor potential ion channels (TRP) render these proteins suitable to act as temperature sensors. Here we test the hypothesis that TRPs are present in reptiles and function to control thermoregulatory behaviour. We show that the hot-sensing TRPV1 is expressed in a crocodile (Crocodylus porosus), an agamid (Amphibolurus muricatus) and a scincid (Pseudemoia entrecasteauxii) lizard, as well as in the quail and zebrafinch (Coturnix chinensis and Poephila guttata). The TRPV1 genes from all reptiles form a unique clade that is delineated from the mammalian and the ancestral Xenopus sequences by an insertion of two amino acids. TRPV1 and the cool-sensing TRPM8 are expressed in liver, muscle (transversospinalis complex), and heart tissues of the crocodile, and have the potential to act as internal thermometer and as external temperatures sensors. Inhibition of TRPV1 and TRPM8 in C. porosus abolishes the typically reptilian shuttling behaviour between cooling and heating environments, and leads to significantly altered body temperature patterns. Our results provide the proximate mechanism of thermal selection in terrestrial ectotherms, which heralds a fundamental change in interpretation, because TRPs provide the mechanism for a tissue-specific input into the animals' thermoregulatory response. PMID- 17356693 TI - Theory versus data: how to calculate R0? AB - To predict the potential severity of outbreaks of infectious diseases such as SARS, HIV, TB and smallpox, a summary parameter, the basic reproduction number R(0), is generally calculated from a population-level model. R(0) specifies the average number of secondary infections caused by one infected individual during his/her entire infectious period at the start of an outbreak. R(0) is used to assess the severity of the outbreak, as well as the strength of the medical and/or behavioral interventions necessary for control. Conventionally, it is assumed that if R(0)>1 the outbreak generates an epidemic, and if R(0)<1 the outbreak becomes extinct. Here, we use computational and analytical methods to calculate the average number of secondary infections and to show that it does not necessarily represent an epidemic threshold parameter (as it has been generally assumed). Previously we have constructed a new type of individual-level model (ILM) and linked it with a population-level model. Our ILM generates the same temporal incidence and prevalence patterns as the population-level model; we use our ILM to directly calculate the average number of secondary infections (i.e., R(0)). Surprisingly, we find that this value of R(0) calculated from the ILM is very different from the epidemic threshold calculated from the population-level model. This occurs because many different individual-level processes can generate the same incidence and prevalence patterns. We show that obtaining R(0) from empirical contact tracing data collected by epidemiologists and using this R(0) as a threshold parameter for a population-level model could produce extremely misleading estimates of the infectiousness of the pathogen, the severity of an outbreak, and the strength of the medical and/or behavioral interventions necessary for control. PMID- 17356694 TI - Genesis of a fungal non-self recognition repertoire. AB - Conspecific allorecognition, the ability for an organism to discriminate its own cells from those of another individual of the same species, has been developed by many organisms. Allorecognition specificities are determined by highly polymorphic genes. The processes by which this extreme polymorphism is generated remain largely unknown. Fungi are able to form heterokaryons by fusion of somatic cells, and somatic non self-recognition is controlled by heterokaryon incompatibility loci (het loci). Herein, we have analyzed the evolutionary features of the het-d and het-e fungal allorecognition genes. In these het genes, allorecognition specificity is determined by a polymorphic WD-repeat domain. We found that het-d and het-e belong to a large gene family with 10 members that all share the WD-repeat domain and show that repeats of all members of the family undergo concerted evolution. It follows that repeat units are constantly exchanged both within and between members of the gene family. As a consequence, high mutation supply in the repeat domain is ensured due to the high total copy number of repeats. We then show that in each repeat four residues located at the protein/protein interaction surface of the WD-repeat domain are under positive diversifying selection. Diversification of het-d and het-e is thus ensured by high mutation supply, followed by reshuffling of the repeats and positive selection for favourable variants. We also propose that RIP, a fungal specific hypermutation process acting specifically on repeated sequences might further enhance mutation supply. The combination of these evolutionary mechanisms constitutes an original process for generating extensive polymorphism at loci that require rapid diversification. PMID- 17356695 TI - Variation in GYS1 interacts with exercise and gender to predict cardiovascular mortality. AB - BACKGROUND: The muscle glycogen synthase gene (GYS1) has been associated with type 2 diabetes (T2D), the metabolic syndrome (MetS), male myocardial infarction and a defective increase in muscle glycogen synthase protein in response to exercise. We addressed the questions whether polymorphism in GYS1 can predict cardiovascular (CV) mortality in a high-risk population, if this risk is influenced by gender or physical activity, and if the association is independent of genetic variation in nearby apolipoprotein E gene (APOE). METHODOLOGY/PRINCIPAL FINDINGS: Polymorphisms in GYS1 (XbaIC>T) and APOE ( 219G>T, epsilon2/epsilon3/epsilon4) were genotyped in 4,654 subjects participating in the Botnia T2D-family study and followed for a median of eight years. Mortality analyses were performed using Cox proportional-hazards regression. During the follow-up period, 749 individuals died, 409 due to CV causes. In males the GYS1 XbaI T-allele (hazard ratio (HR) 1.9 [1.2-2.9]), T2D (2.5 [1.7-3.8]), earlier CV events (1.7 [1.2-2.5]), physical inactivity (1.9 [1.2 2.9]) and smoking (1.5 [1.0-2.3]) predicted CV mortality. The GYS1 XbaI T-allele predicted CV mortality particularly in physically active males (HR 1.7 [1.3 2.0]). Association of GYS1 with CV mortality was independent of APOE (219TT/epsilon4), which by its own exerted an effect on CV mortality risk in females (2.9 [1.9-4.4]). Other independent predictors of CV mortality in females were fasting plasma glucose (1.2 [1.1-1.2]), high body mass index (BMI) (1.0 [1.0 1.1]), hypertension (1.9 [1.2-3.1]), earlier CV events (1.9 [1.3-2.8]) and physical inactivity (1.9 [1.2-2.8]). CONCLUSIONS/SIGNIFICANCE: Polymorphisms in GYS1 and APOE predict CV mortality in T2D families in a gender-specific fashion and independently of each other. Physical exercise seems to unmask the effect associated with the GYS1 polymorphism, rendering carriers of the variant allele less susceptible to the protective effect of exercise on the risk of CV death, which finding could be compatible with a previous demonstration of defective increase in the glycogen synthase protein in carriers of this polymorphism. PMID- 17356696 TI - A practical genome scan for population-specific strong selective sweeps that have reached fixation. AB - Phenotypic divergences between modern human populations have developed as a result of genetic adaptation to local environments over the past 100,000 years. To identify genes involved in population-specific phenotypes, it is necessary to detect signatures of recent positive selection in the human genome. Although detection of elongated linkage disequilibrium (LD) has been a powerful tool in the field of evolutionary genetics, current LD-based approaches are not applicable to already fixed loci. Here, we report a method of scanning for population-specific strong selective sweeps that have reached fixation. In this method, genome-wide SNP data is used to analyze differences in the haplotype frequency, nucleotide diversity, and LD between populations, using the ratio of haplotype homozygosity between populations. To estimate the detection power of the statistics used in this study, we performed computer simulations and found that these tests are relatively robust against the density of typed SNPs and demographic parameters if the advantageous allele has reached fixation. Therefore, we could determine the threshold for maintaining high detection power, regardless of SNP density and demographic history. When this method was applied to the HapMap data, it was able to identify the candidates of population-specific strong selective sweeps more efficiently than the outlier approach that depends on the empirical distribution. This study, confirming strong positive selection on genes previously reported to be associated with specific phenotypes, also identifies other candidates that are likely to contribute to phenotypic differences between human populations. PMID- 17356697 TI - Redundancy in genotyping arrays. AB - Despite their unprecedented density, current SNP genotyping arrays contain large amounts of redundancy, with up to 40 oligonucleotide features used to query each SNP. By using publicly available reference genotype data from the International HapMap, we show that 93.6% sensitivity at <5% false positive rate can be obtained with only four probes per SNP, compared with 98.3% with the full data set. Removal of this redundancy will allow for more comprehensive whole-genome association studies with increased SNP density and larger sample sizes. PMID- 17356698 TI - ADRB2 Arg16Gly polymorphism, lung function, and mortality: results from the Atherosclerosis Risk in Communities study. AB - BACKGROUND: Growing evidence suggests that the Arg16Arg genotype of the beta-2 adrenergic receptor gene may be associated with adverse effects of beta-agonist therapy. We sought to examine the association of beta-agonist use and the Arg16Gly polymorphism with lung function and mortality among participants in the Atherosclerosis Risk in Communities study. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped study participants and analyzed the association of the Arg16Gly polymorphism and beta-agonist use with lung function at baseline and clinical examination three years later and with all-cause mortality during 10 years of follow-up. Lung function was characterized by percent-predicted forced expiratory volume in 1 second. Associations were examined separately for blacks and whites. Black beta-agonist users with the Arg/Arg genotype had better lung function at baseline and at the second clinical visit than those with Arg/Gly and Gly/Gly genotypes. Adjusted mean percent-predicted FEV(1) was 21% higher in Arg/Arg subjects compared to Gly/Gly at baseline (p = 0.01) and 20% higher than Gly/Gly at visit 2 (p = 0.01). Arg/Gly subjects had adjusted percent-predicted FEV(1) 17% lower than Arg/Arg at baseline but were similar to Arg/Arg subjects at visit 2. Although black beta-agonist users with the Arg/Arg genotype appeared to have better crude survival rates, the association between genotype and all-cause mortality was inconclusive. We found no difference in lung function or mortality by genotype among blacks who did not use beta-agonists or among whites, regardless of beta-agonist use. CONCLUSIONS: Black beta-agonist users with the ADRB2 Arg16Arg genotype had better lung function, and, possibly, better overall survival compared to black beta-agonist users with the Gly16Gly genotype. Our findings highlight the need for additional studies of sufficient size and statistical power to allow examination of outcomes among beta-agonist users of different races and genotypes. PMID- 17356699 TI - Stability of mRNA/DNA and DNA/DNA duplexes affects mRNA transcription. AB - Nucleic acids, due to their structural and chemical properties, can form double stranded secondary structures that assist the transfer of genetic information and can modulate gene expression. However, the nucleotide sequence alone is insufficient in explaining phenomena like intron-exon recognition during RNA processing. This raises the question whether nucleic acids are endowed with other attributes that can contribute to their biological functions. In this work, we present a calculation of thermodynamic stability of DNA/DNA and mRNA/DNA duplexes across the genomes of four species in the genus Saccharomyces by nearest-neighbor method. The results show that coding regions are more thermodynamically stable than introns, 3'-untranslated regions and intergenic sequences. Furthermore, open reading frames have more stable sense mRNA/DNA duplexes than the potential antisense duplexes, a property that can aid gene discovery. The lower stability of the DNA/DNA and mRNA/DNA duplexes of 3'-untranslated regions and the higher stability of genes correlates with increased mRNA level. These results suggest that the thermodynamic stability of DNA/DNA and mRNA/DNA duplexes affects mRNA transcription. PMID- 17356700 TI - Tetrahymena metallothioneins fall into two discrete subfamilies. AB - BACKGROUND: Metallothioneins are ubiquitous small, cysteine-rich, multifunctional proteins which can bind heavy metals. METHODOLOGY/PRINCIPAL FINDINGS: We report the results of phylogenetic and gene expression analyses that include two new Tetrahymena thermophila metallothionein genes (MTT3 and MTT5). Sequence alignments of all known Tetrahymena metallothioneins have allowed us to rationalize the structure of these proteins. We now formally subdivide the known metallothioneins from the ciliate genus Tetrahymena into two well defined subfamilies, 7a and 7b, based on phylogenetic analysis, on the pattern of clustering of Cys residues, and on the pattern of inducibility by the heavy metals Cd and Cu. Sequence alignment also reveals a remarkably regular, conserved and hierarchical modular structure of all five subfamily 7a MTs, which include MTT3 and MTT5. The former has three modules, while the latter has only two. Induction levels of the three T. thermophila genes were determined using quantitative real time RT-PCR. Various stressors (including heavy metals) brought about dramatically different fold-inductions for each gene; MTT5 showed the highest fold-induction. Conserved DNA motifs with potential regulatory significance were identified, in an unbiased way, upstream of the start codons of subfamily 7a MTs. EST evidence for alternative splicing in the 3' UTR of the MTT5 mRNA with potential regulatory activity is reported. CONCLUSION/SIGNIFICANCE: The small number and remarkably regular structure of Tetrahymena MTs, coupled with the experimental tractability of this model organism for studies of in vivo function, make it an attractive system for the experimental dissection of the roles, structure/function relationships, regulation of gene expression, and adaptive evolution of these proteins, as well as for the development of biotechnological applications for the environmental monitoring of toxic substances. PMID- 17356701 TI - Increased expression of the auxiliary beta(2)-subunit of ventricular L-type Ca(2)+ channels leads to single-channel activity characteristic of heart failure. AB - BACKGROUND: Increased activity of single ventricular L-type Ca(2+)-channels (L VDCC) is a hallmark in human heart failure. Recent findings suggest differential modulation by several auxiliary beta-subunits as a possible explanation. METHODS AND RESULTS: By molecular and functional analyses of human and murine ventricles, we find that enhanced L-VDCC activity is accompanied by altered expression pattern of auxiliary L-VDCC beta-subunit gene products. In HEK293-cells we show differential modulation of single L-VDCC activity by coexpression of several human cardiac beta-subunits: Unlike beta(1) or beta(3) isoforms, beta(2a) and beta(2b) induce a high-activity channel behavior typical of failing myocytes. In accordance, beta(2)-subunit mRNA and protein are up-regulated in failing human myocardium. In a model of heart failure we find that mice overexpressing the human cardiac Ca(V)1.2 also reveal increased single-channel activity and sarcolemmal beta(2) expression when entering into the maladaptive stage of heart failure. Interestingly, these animals, when still young and non-failing ("Adaptive Phase"), reveal the opposite phenotype, viz: reduced single-channel activity accompanied by lowered beta(2) expression. Additional evidence for the cause-effect relationship between beta(2)-subunit expression and single L-VDCC activity is provided by newly engineered, double-transgenic mice bearing both constitutive Ca(V)1.2 and inducible beta(2) cardiac overexpression. Here in non failing hearts induction of beta(2)-subunit overexpression mimicked the increase of single L-VDCC activity observed in murine and human chronic heart failure. CONCLUSIONS: Our study presents evidence of the pathobiochemical relevance of beta(2)-subunits for the electrophysiological phenotype of cardiac L-VDCC and thus provides an explanation for the single L-VDCC gating observed in human and murine heart failure. PMID- 17356702 TI - Precancerous stem cells have the potential for both benign and malignant differentiation. AB - Cancer stem cells (CSCs) have been identified in hematopoietic and solid tumors. However, their precursors-namely, precancerous stem cells (pCSCs) -have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into cancer, they often develop, however, into leukemic or solid cancers composed of various types of cancer cells in immunodeficient mice. The progress of the pCSCs to cancers is associated with the up-regulation of c-kit and Sca-1, as well as with lineage markers. Mechanistically, the pCSCs are regulated by the PIWI/AGO family gene called piwil2. Our results provide clear evidence that a single clone of pCSCs has the potential for both benign and malignant differentiation, depending on the environmental cues. We anticipate pCSCs to be a novel target for the early detection, prevention, and therapy of cancers. PMID- 17356703 TI - Invasions and extinctions reshape coastal marine food webs. AB - The biodiversity of ecosystems worldwide is changing because of species loss due to human-caused extinctions and species gain through intentional and accidental introductions. Here we show that the combined effect of these two processes is altering the trophic structure of food webs in coastal marine systems. This is because most extinctions ( approximately 70%) occur at high trophic levels (top predators and other carnivores), while most invasions are by species from lower trophic levels (70% macroplanktivores, deposit feeders, and detritivores). These opposing changes thus alter the shape of marine food webs from a trophic pyramid capped by a diverse array of predators and consumers to a shorter, squatter configuration dominated by filter feeders and scavengers. The consequences of the simultaneous loss of diversity at top trophic levels and gain at lower trophic levels is largely unknown. However, current research suggests that a better understanding of how such simultaneous changes in diversity can impact ecosystem function will be required to manage coastal ecosystems and forecast future changes. PMID- 17356704 TI - Tripotential differentiation of adherently expandable neural stem (NS) cells. AB - BACKGROUND: A recent study has shown that pure neural stem cells can be derived from embryonic stem (ES) cells and primary brain tissue. In the presence of fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF), this population can be continuously expanded in adherent conditions. In analogy to continuously self-renewing ES cells, these cells were termed 'NS' cells (Conti et al., PLoS Biol 3: e283, 2005). While NS cells have been shown to readily generate neurons and astrocytes, their differentiation into oligodendrocytes has remained enigmatic, raising concerns as to whether they truly represent tripotential neural stem cells. METHODOLOGY/PRINCIPAL FINDINGS: Here we provide evidence that NS cells are indeed tripotent. Upon proliferation with FGF2, platelet-derived growth factor (PDGF) and forskolin, followed by differentiation in the presence of thyroid hormone (T3) and ascorbic acid NS cells efficiently generate oligodendrocytes ( approximately 20%) alongside astrocytes ( approximately 40%) and neurons ( approximately 10%). Mature oligodendroglial differentiation was confirmed by transplantation data showing that NS cell-derived oligodendrocytes ensheath host axons in the brain of myelin-deficient rats. CONCLUSIONS/SIGNIFICANCE: In addition to delineating NS cells as a potential donor source for myelin repair, our data strongly support the view that these adherently expandable cells represent bona fide tripotential neural stem cells. PMID- 17356705 TI - Distribution of menin-occupied regions in chromatin specifies a broad role of menin in transcriptional regulation. AB - Menin is the protein product of the MEN1 tumor-suppressor gene; one allele of MEN1 is inactivated in the germ line of patients with "multiple endocrine neoplasia type 1" (MEN1) cancer syndrome. Menin interacts with several proteins involved in transcriptional regulation. RNA expression analyses have identified several menin-regulated genes that could represent proximal or distal interaction sites for menin. This report presents a substantial and unbiased sampling of menin-occupied chromatin regions using Serial Analysis of Chromatin Occupancy; this method combines chromatin immuno-precipitation with Serial Analysis of Gene Expression. Hundreds of menin-occupied genomic sites were identified in promoter regions (32% of menin-occupied loci), near the 3' end of genes (14%), or inside genes (21%), extending other data about menin recruitments to many sites of transcriptional activity. A large number of menin-occupied sites (33%) were located outside known gene regions. Additional annotation of the human genome could help in identifying genes at these loci, or these might be gene-free regions of the genome where menin occupancy could play some structural or regulatory role. Menin occupancy at many intragenic positions distant from the core promoter reveals an unexpected type of menin target region at many loci in the genome. These unbiased data also suggest that menin could play a broad role in transcriptional regulation. PMID- 17356706 TI - Early effects of combretastatin-A4 disodium phosphate on tumor perfusion and interstitial fluid pressure. AB - Combretastatin-A4 disodium phosphate (CA4DP) is a vascular-disruptive agent that causes an abrupt decrease in tumor blood flow. The direct actions of CA4DP include increases in vascular permeability and destabilization of the endothelial cytoskeleton, which are thought to contribute to occlusion of the tumor vasculature. It has been proposed that increased permeability causes a transient increase in interstitial fluid pressure (IFP), which in turn could collapse intratumoral blood vessels. We examined the immediate effects of CA4DP on tumor IFP in C3H mammary carcinoma. Mice were treated with 100 mg/kg CA4DP by intraperitoneal injection. Tumor perfusion was recorded by laser Doppler flowmetry at separate time points, and IFP was recorded continuously by the wick in-needle method. In this study, we found that CA4DP treatment resulted in a rapid reduction in tumor perfusion, followed by a decrease in IFP; no increases in IFP were observed. This suggests that CA4DP-induced reductions in tumor perfusion are not dependent on increases in IFP. PMID- 17356707 TI - Inhibition of skeletal metastasis by ectopic ERalpha expression in ERalpha negative human breast cancer cell lines. AB - Some hormone-independent breast cancers lack functional estrogen receptors (ERs) and show evidence of a more aggressive metastatic phenotype. A protective role of the ER has also been suggested in hormone-resistant breast cancer progression. In this study, we have investigated the effect of the ectopic expression of human ERalpha on the bone-metastatic potential of highly metastatic ERalpha-negative human breast cancer MDA-MB-231 and MDA-MB-435-F-L cell lines in an experimental model of bone metastasis in nude mice. ERalpha overexpression had no effect on the growth of both cell lines but reduced the expression of integrin alpha(v)beta(3) and the receptor activator of NF-kappaB, which are known to promote bone metastasis. A significant reduction in the incidence of osteolytic bone metastasis was observed by X-ray imaging of the legs and arms of mice inoculated with ERalpha-expressing clones of MDA-MB-231 cells in comparison to controls. Ectopic expression of ERalpha in MDA-MB-435-F-L cells also reduced their widespread skeletal metastasis to the legs, arms, spine, and mandible, as detected by whole-mouse enhanced green fluorescent protein imaging. Our study indicates for the first time that stable reintroduction of functional ERalpha in ERalpha-negative human breast cancer cells can inhibit their aggressive bone metastatic potential in an experimental bone metastasis model. PMID- 17356708 TI - Target therapy using a small molecule inhibitor against angiogenic receptors in pancreatic cancer. AB - PURPOSE: PD173074, a small molecule inhibitor of VEGF-RII and FGF-RI, targets neoangiogenesis and mitogenesis. This study aimed to analyze a single-compound driven inhibition of FGF and VEGF receptors in pancreatic cancer. EXPERIMENTAL DESIGN: RT-PCR and Western blots were performed to quantify protein expression and phosphorylation. Anchorage dependent and independent growth assays were used to study cell growth. With flow cytometry, cell cycle analysis and apoptosis were studied. In vivo HPAF-II and MIA PaCa-2 cells were xenografted. Animals were treated daily for 10 weeks. Immunohistochemistry was used to quantify microvessel density and apoptosis. RESULTS: Highest levels of FGF-RI were detectable in MIA PaCa-2 cells, lowest in HPAF-II cells. PD173074 inhibited cell growth most prominently in cells expressing high levels of FGF-RI. Cell cycle progression was inhibited by blocking transition in the G(0)/G(1) phase, and consequently, apoptosis was increased. In vivo significant inhibition of orthotopic tumor growth was achieved by a combination effect of inhibition of mitogenesis, induction of apoptosis, and reduction of angiogenesis in PD173074-treated animals. CONCLUSIONS: These data highlight VEGF-RII and FGF-RI as therapeutic targets and suggest a potential role for the combined use of tyrosine kinase inhibitors in the management of inoperable pancreatic cancer patients. PMID- 17356709 TI - Visualizing the acute effects of vascular-targeted therapy in vivo using intravital microscopy and magnetic resonance imaging: correlation with endothelial apoptosis, cytokine induction, and treatment outcome. AB - The acute effects of the vascular-disrupting agent 5,6-dimethylxanthenone-4 acetic acid (DMXAA) were investigated in vivo using intravital microscopy (IVM) and magnetic resonance imaging (MRI). Changes in vascular permeability and blood flow of syngeneic CT-26 murine colon adenocarcinomas were assessed at 4 and 24 hours after DMXAA treatment (30 mg/kg, i.p.) and correlated with induction of tumor necrosis factor-alpha (TNF-alpha), endothelial damage [CD31/terminal deoxynucleotidyl transferase (TdT)], and treatment outcome. Intravital imaging revealed a marked increase in vascular permeability 4 hours after treatment, consistent with increases in intratumoral mRNA and protein levels of TNF-alpha. Parallel contrast-enhanced MRI studies showed a approximately 4-fold increase in longitudinal relaxation rates (DeltaR(1)), indicative of increased contrast agent accumulation within the tumor. Dual immunostained tumor sections (CD31/TdT) revealed evidence of endothelial apoptosis at this time point. Twenty-four hours after treatment, extensive hemorrhage and complete disruption of vascular architecture were observed with IVM, along with a significant reduction in DeltaR(1); and virtual absence of CD31 immunostaining. DMXAA-induced tumor vascular damage resulted in significant long-term (60-day) cures compared to untreated controls. Multimodality imaging approaches are useful in visualizing the effects of antivascular therapy in vivo. Such approaches allow cross validation and correlation of findings with underlying molecular changes contributing to treatment outcome. PMID- 17356710 TI - Genes and proteins differentially expressed during in vitro malignant transformation of bovine pancreatic duct cells. AB - Pancreatic carcinoma has an extremely bad prognosis due to lack of early diagnostic markers and lack of effective therapeutic strategies. Recently, we have established an in vitro model recapitulating the first steps in the carcinogenesis of the pancreas. SV40 large T antigen-immortalized bovine pancreatic duct cells formed intrapancreatic adenocarcinoma tumors on k-ras(mut) transfection after orthotopic injection in the nude mouse pancreas. Here we identified genes and proteins differentially expressed in the course of malignant transformation using reciprocal suppression subtractive hybridization and 2D gel electrophoresis and mass spectrometry, respectively. We identified 34 differentially expressed genes, expressed sequence tags, and 15 unique proteins. Differential expression was verified for some of the genes or proteins in samples from pancreatic carcinoma. Among these genes and proteins, the majority had already been described either to be influenced by a mutated ras or to be differentially expressed in pancreatic adenocarcinoma, thus proving the feasibility of our model. Other genes and proteins (e.g., BBC1, GLTSCR2, and rhoGDIalpha), up to now, have not been implicated in pancreatic tumor development. Thus, we were able to establish an in vitro model of pancreatic carcinogenesis, which enabled us to identify genes and proteins differentially expressed during the early steps of malignant transformation. PMID- 17356711 TI - Estrogen and resveratrol regulate Rac and Cdc42 signaling to the actin cytoskeleton of metastatic breast cancer cells. AB - Estrogen and structurally related molecules play critical roles in breast cancer. We reported that resveratrol (50 microM), an estrogen-like phytosterol from grapes, acts in an antiestrogenic manner in breast cancer cells to reduce cell migration and to induce a global and sustained extension of actin structures called filopodia. Herein, we report that resveratrol-induced filopodia formation is time-dependent and concentration-dependent. In contrast to resveratrol at 50 microM, resveratrol at 5 microM acts in a manner similar to estrogen by increasing lamellipodia, as well as cell migration and invasion. Because Rho GTPases regulate the extension of actin structures, we investigated a role for Rac and Cdc42 in estrogen and resveratrol signaling. Our results demonstrate that 50 microM resveratrol decreases Rac and Cdc42 activity, whereas estrogen and 5 microM resveratrol increase Rac activity in breast cancer cells. MDA-MB-231 cells expressing dominant-negative Cdc42 or dominant-negative Rac retain filopodia response to 50 microM resveratrol. Lamellipodia response to 5 microM resveratrol, estrogen, or epidermal growth factor is inhibited in cells expressing dominant negative Rac, indicating that Rac regulates estrogen and resveratrol (5 microM) signaling to the actin cytoskeleton. These results indicate that signaling to the actin cytoskeleton by low and high concentrations of resveratrol may be differentially regulated by Rac and Cdc42. PMID- 17356713 TI - Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. AB - DNA microarrays have been widely applied to cancer transcriptome analysis; however, the majority of such data are not easily accessible or comparable. Furthermore, several important analytic approaches have been applied to microarray analysis; however, their application is often limited. To overcome these limitations, we have developed Oncomine, a bioinformatics initiative aimed at collecting, standardizing, analyzing, and delivering cancer transcriptome data to the biomedical research community. Our analysis has identified the genes, pathways, and networks deregulated across 18,000 cancer gene expression microarrays, spanning the majority of cancer types and subtypes. Here, we provide an update on the initiative, describe the database and analysis modules, and highlight several notable observations. Results from this comprehensive analysis are available at http://www.oncomine.org. PMID- 17356714 TI - A novel tetrameric lectin from Lycoris aurea with four mannose binding sites per monomer. AB - The mannose-binding agglutinin from bulbs of Lycoris aurea (LAA) agglutinates rabbit but not human erythrocytes. The molecular mass of the monomer in SDS/PAGE is 12 kDa while the apparent molecular mass in gel filtration is 48 kDa, indicating that LAA is a homotetramer. The full-length cDNA of LAA contains 683 bp with an open reading frame encoding a protomer of 162 amino-acid residues. Hydrophobic Cluster Analysis and molecular modeling of the 109-residue mature polypeptide suggested a similar secondary and tertiary structure to those of Narcissus pseudonarcissus agglutinin (NPA). Molecular docking revealed that, besides the three mannose-binding sites common among Amaryllidaceae lectins, LAA also contains a fourth unique mannose-binding site formed by a tryptophan cluster. The existence of four mannose-binding sites in each monomer of LAA is very unusual and has only been reported for NPA earlier. PMID- 17356712 TI - GNAS1 T393C polymorphism is associated with clinical course in patients with intrahepatic cholangiocarcinoma. AB - BACKGROUND/AIMS: The GNAS1 locus encodes the Galphas protein, which stimulates the formation of cyclo-adenosinemonophosphate (cAMP). The cAMP pathway mediates pleiotropic effects, including the regulation of apoptosis and proliferation. We have recently shown that TT genotypes of the single-nucleotide polymorphism T393C in the gene GNAS1 predict the clinical outcome of patients with various carcinomas. METHODS: Eighty-seven patients with intrahepatic cholangiocarcinoma (ICC) were retrospectively genotyped to elucidate a potential association between T393C genotypes and clinical outcome. RESULTS: ICCs of patients with homozygous TT genotypes revealed a higher proliferation rate and a lower apoptotic rate. Homozygous TT patients were at highest risk for cancer-related deaths (hazard ratio = 2.74; 95% confidence interval = 1.03-7.28) compared with C-allele carriers. Kaplan-Meier curves for disease-specific overall and local recurrence free survival in a subgroup with R(0)-resected ICC showed a significant association of T393 homozygosity with outcome, which was confirmed in multivariate Cox regression analysis. CONCLUSIONS: GNAS1 T393C is a novel independent host factor for disease progression in patients with ICC. Our finding that TT homozygosity (and not CC homozygosity) was associated with unfavorable clinical outcome points to the complex and differing functional effects induced by GNAS1 T393C polymorphism in various human carcinomas. PMID- 17356715 TI - In vitro DNA binding of purified CcpA protein from Lactococcus lactis IL1403. AB - During this study His-tagged CcpA protein purified under native conditions to obtain a biologically active protein was used for molecular analysis of CcpA dependent regulation. Using electrophoretic mobility shift assays it was demonstrated that CcpA of L. lactis can bind DNA in the absence of the HPr-Ser-P corepressor and exhibits DNA-binding affinity for nucleotide sequences lacking cre sites. However, purified HPr-Ser-P protein from Bacillus subtilis was shown to slightly increase the DNA-binding capacity of the CcpA protein. It was also observed that CcpA bound to the cre box forms an apparently more stable complex than that resulting from unspecific binding. Competition gel retardation assay performed on DNA sequences from two PEP:PTS regions demonstrated that the ybhE, bglS, rheB, yebE, ptcB and yecA genes situated in these regions are most probably directly regulated by CcpA. PMID- 17356716 TI - [Compulsive alcoholics and serotoninergic function]. AB - OBJECTIVE: Different alcoholism subtypes from Jellinek's modified typology reviewed by Babor of gamma and delta alcoholics and former one group (compulsive alcoholics) relationships with serotonergic function are the main purpose of this work, presenting in that sense our study with sertraline at obsessive compulsive disorder treatment doses. METHOD: Open label multicenter six month study with 91 alcohol dependent patients (53% gamma, 20% delta, 27% mixed) treated with sertraline 200 mg to evaluate its effectiveness and tolerance in both subgroups, focusing specially on compulsive alcoholics. Obsessive Compulsive Drinking Scale (OCDS), Barratt Impulsivity Scale (BIS), Craving Evaluation and Clinical Global Impression of Severity (CGI S). CONCLUSIONS: Gamma patients showed a slight tendency to recovery than delta, without statistical significance. These results could reflect a statistical bias, as few delta patients were included. According to neurobiological hypotheses, future studies should try to evaluate these types of alcoholism. Improvement (CGI-I) were the measures employed. RESULTS: CGI S and CGI I showed a statistically significant improvement. Seventy six per cent of patients were responders. No statistically significant differences were observed between gamma and delta groups. PMID- 17356717 TI - [Bipolar disorder in Spain: functional status and resource use on the basis of the Spanish sample of the observational, Pan European EMBLEM study]. AB - RATIONALE: There are very few data as to the social and occupational adaptation of patients with bipolar disorder in Spain and even less is known about the resource use they generate. OBJECTIVE: To determine the functional status and healthcare resource use of the Spanish sample of the pan European EMBLEM (European Mania in Bipolar Longotudinal Evaluation of Medication) study of bipolar patients in manic or mixed phase. METHOD: The EMBLEM study recruited 3536 patients, 312 of whom (8.82%) were enrolled in Spain. Patients had to be adults with a diagnosis of bipolar disorder who were initiating at the discretion of their treating psychiatrist oral treatment for an acute manic phase. They were evaluated using the Spanish versions of rating scales for the severity of mania (Young Mania Rating Scale), bipolar disorder (CGI BD) for mania, depression and hallucinations delusions, and depression (HAMD 5 item version of the Hamilton Scale); the Life Chart Method (LCM) and 2 items of the SLICE of LIFE were used to evaluate functioning. Information was collected on healthcare resource utilization during the preceding year. RESULTS: Sixty three percent of the patients presented with moderate to very severe work related difficulties in the year preceding his her manic episode. Forty percent of the patients failed to comply either totally or partly with their prescribed treatment. Subjects required an average of 1.5 hospitalizations during the year prior to enrollment, with a mean stay of approximately 10 days, and between 7 and 8 outpatient visits per year. PMID- 17356718 TI - [Prevalence of anxiety disorders in patients with essential hypertension]. AB - BACKGROUND: Various studies found a high correlation among anxious symptomatology and hypertension. OBJECTIVES: To determine and to compare prevalence of anxiety disorder among patients with essential hypertension and a control group. METHODS: The structured clinical interview (SCID I) was administered (anxiety disorder module) to 157 people including 57 essential hypertensive patients (non diabetics, without CVA and or other complications) and 100 controls (non hypertensive people that converge to the hospital). RESULTS: We observed a higher frequency of anxiety disorder in the hypertensive group than in the control group (p <0.001). PMID- 17356719 TI - [Endocannabinoids: the inside plant]. AB - An endogenous compound that binds to the same receptor sites activated by the main psychoactive constituent of marihuana, delta 9 tetrahydrocannabinol (THC), is synthetised in the brain and in several peripheral tissues. The endogenous cannabinoid was named anandamide on the basis of the sanscrit word ananda, that means bringer of inner bliss . Anandamide reproduces marihuana effects,is synthetised in response to physical activity, and is involved in neurobiologic mechanisms common to drug addiction. Cannabinoid CB1 receptors, and their endogenous ligands, are present in brain areas linked to reward circuits. The blockade of CB1 receptors causes anorexia and is being employed to treat obesity. On the contrary, activation of CB1 receptors has appetite stimulant, antiemetic and analgesic properties, that deserve to be studied for putative therapeutical uses. PMID- 17356720 TI - [From belief to prejudice]. AB - The world in which our reality is to be set up, needs to be organized. Knowledge of this world is not acquired just by experience but by complex relation between what was lived, and discourses, whether preceding or ensuing experience, that render it both signifying and articulate. In other words, knowledge is not possible in the absence of a discourse that warrants and organizes perception. And, it is the institutive discourse of another human by which the mode of relation with the world that implies organizations and valuations is made possible. A discourse is called into play that not only organizes and marks the limits but also institutes identities, which can only be accomplished by means of differentiation. The other human, however, does not only transmit the adaptative, but also the "unadapted" of the species: the neurotic inscriptions of the lived reality, the generational experiences that account for the constitution of those that took the child into their care, the judgements and prejudices that appear as irreducible, operating as limited blocks that experience is unable to dissolve, and can even transform the prejudiced object in that that was previously imposed as its dominant trait. The present work endeavours to make a distinction between belief and prejudice, by addressing the question both from the epistemological and the psychodynamic angles, with due attention to the ethical and moral implications of such distinction. PMID- 17356721 TI - [On terms necessary, yet insufficient]. AB - The article attempts a review of several problems dealing with discourses which rely in the struggle against prejudice and discrimination as an appropriate means for emancipatory purposes. The historicity inherent to claims of equality fighting against discriminatory practices makes reference to historically specific social networks. Globalization tends to standardize equalitarian discourses which then join cultural contexts in which they lack their own genealogy. In countries such as Argentina, this is what happens with the so called politically correct. While in its original environment it has shown its pros and cons regarding emancipatory fights, among us instead it presents itself as an alien import that entails as well those critical attitudes that have informed its recent history, especially those satirical in nature. In a satirical stance, emancipatory struggles find a way to pass over such limits and a modality of great narrative richness intended to recover the highest values at the expense of more crystallized and dogmatic ones. By means of satire, these struggles rediscover cultural traditions of ancient lineage in which is rooted the ethical reserve that supports them. PMID- 17356722 TI - [Prejudice, women, and psychiatry. As crazy as your mom]. AB - If being named somehow is condition of human existencies and to a certain extent also makes them determinate, then the dimension of prejudice is perhaps irreducible; at least in this sense, as a previous idea being the site of understanding, reflection and production. The present work starts from the ideas of the production and transformation of reality produced by the theoretical developments that describe and legitimate the practice of a certain discipline and the notion of gender as a socio historical category referring to the social relations of power and subordination established between males and females and are translated, through an extrapolative operation, into social inequalities. By going through the psychoanalytic conceptualisation of the Oedipus Complex in women, an understanding is made possible of some prejudices affecting psychiatrists in thier practice with women pacients. An attempt to read from a particular theoretical framework that makes these women what is called mad, starts from the history of those that name them in such a manner, with reference to the nexus with the mother. Such nexus is transited by each, with a better or worse destiny. Taking into account the responsibility of a determinate creation of subjectivity from the position of subject of the enunciation that is produced in the daily task from a particular ethical position. PMID- 17356723 TI - Alexey Kondratyevich Savrasov (1830-1897): the muse and the bottle. AB - The Russian landscape painter Alexey Savrasov lived in the middle of the 19th century. He was overwhelmed with grief at the loss of several of his children and he used alcohol to blunt the pain and anguish. The effects of psychoactive substances and especially alcohol have been linked closely to creativity. His life story demonstrates the bitter relationship between the bottle and the muse. He became dependent on alcohol, his family broke up and he was fired from work, his creativity declined and his health deteriorated. At death, he was a lonely and a forgotten man and only two persons attended his funeral. PMID- 17356724 TI - Waldemar Mordecai Haffkine, CIE (1860-1930): prophylactic vaccination against cholera and bubonic plague in British India. AB - Waldemar Mordecai Haffkine developed an anticholera vaccine at the Pasteur Institute, Paris, in 1892. From the results of field trials in India from 1893 to 1896, he has been credited as having carried out the first effective prophylactic vaccination for a bacterial disease in man. When the plague pandemic reached Bombay, Haffkine became bacteriologist to the Government of (British) India (1896 1915). He soon produced an effective antiplague vaccine and large inoculation schemes were commenced. In 1902 19 people in Mulkowal (Punjab) died from tetanus poisoning as a consequence of antiplague vaccination. Haffkine was blamed unjustly and exonerated only in 1907, following a campaign spear-headed by Ronald Ross. In India the stigma remained. In 1925 in tribute to the great bacteriologist, the Bombay Government renamed the laboratory as the Haffkine Institute. The Haffkine Biopharmaceutical Corporation Ltd and the Haffkine Institute for Training, Research and Testing in Mumbai continue to be important centres for public health. PMID- 17356725 TI - The Stathams of Stone and Islington. AB - The story of the Statham family and their connections with Buckinghamshire and London centres around the figure of Sherard Freeman Statham (1826-1858), the founder of the Royal Northern Hospital. Born into an impoverished branch of an ancient landowning family, his circumstances were abruptly bettered when his clergyman father (a somewhat controversial character) made a lucrative marriage. Statham qualified in medicine with high honours and went on to become a brilliant young surgeon and teacher, and his future seemed assured. But his hasty and aggressive nature led to his dismissal from University College Hospital. Unsatisfied by private practice, he almost single-handedly founded a new hospital to serve the poor of North London, which went on to flourish as a well-respected surgical centre until its eventual closure in 1992. However, Statham never saw the success of his enterprise as he died from tuberculosis at the age of 32. PMID- 17356726 TI - Samuel James (c1763-1831) of Hoddesdon and the medicinal use of willow bark. AB - Recognition of the medicinal properties of extracts of willow (Salix sp) bark is usually attributed to Edward Stone (1702-68) of Chipping Norton in Oxfordshire. It was the search for the medicinal compounds that they contained that eventually led to the discovery of salicylic acid, the parent compound of aspirin. Little attention has been given to the work of Samuel James of Hoddesdon who confirmed and extended the results of Stone and who influenced later chemists in their search for specific compounds. Here his work is described and evaluated and his biographical details are recorded. PMID- 17356727 TI - The life and work of Felix Post (1913-2001): pioneer in the psychiatry of old age. AB - Felix Post was a refugee from Nazi Europe. Appointed psychiatrist at the Maudsley Hospital, London in 1947, he pioneered treatment of mental illness in older people clinically and through meticulous research. He had a reputation as a brilliant clinical teacher. His work helped set the scientific foundations for the development of the specialty of old age psychiatry in Britain and he inspired junior doctors who worked with him to specialize in the newly emerging discipline. PMID- 17356728 TI - George Guthrie (1785-1856): surgeon to the Duke of Wellington, and a pioneer thoracic surgeon. AB - George Guthrie had a distinguished career as a soldier, surgeon and medical reformer. He revolutionized military surgery following his active service during the Peninsular War in Spain and Portugal. His book Commentaries on the Surgery of War was based on this experience and was updated continuously; it remained the standard military text for half a century. During this campaign, he also struggled to improve the poor administration of the Army Medical Service. He had little respect for established dogma and was a man of great humanity and integrity who based his opinion on personal statistical observation together with his own anatomical and postmortem studies. His influence on surgical thinking was enormous and he was three times the President of the Royal College of Surgeons of England. PMID- 17356729 TI - Sir Victor Horsley (1857-1916) and the birth of English neurosurgery. AB - Modern surgery developed in the second half of the 19th century, at the end of which neurosurgery was established as a profitable region of operative intervention. In the British Isles, the first exponent was Sir William Macewen (1848-1924) in Glasgow. But neuroscience had advanced in London due to the excellence of the neurologists in the several hospitals there. Foremost among English neurosurgeons was Victor Horsley whose career had a worldwide influence on the speciality. Initially, operations were carried out for cranial trauma, the removal of displaced bone or blood clot, and the drainage of abscesses arising from infection of the middle ears and air sinuses. The diagnosis of brain and spinal tumours by neurologists encouraged removal by surgeons, of which Horsley was among the earliest. Horsley performed many operations on animals, experiments opposed by the anti-vivisectionists whose campaigns Horsley countered. Horsley had many other interests, some of which displeased the establishment, and in World War I his experience in neurosurgery was not used. He served as a general surgeon, visiting Egypt, India and Mesopotamia where, in Amara, he died from hyperpyrexia complicating bacillary dysentery. PMID- 17356730 TI - Smith-Petersen's pin for femoral neck fractures. PMID- 17356731 TI - The Grellier twins, Norman (1886-1949) and Bernard (1886-1957), radiologists of East Sussex. AB - Identical twins Bernard and Norman Grellier (born Epsom, 1886) attended Epsom College before entering Dental School at the Royal Dental Hospital of London in 1904, graduating in 1910. Then they trained in medicine at Charing Cross Hospital. Bernard graduated in 1913 and Norman in 1915. In 1915 they joined the Royal Army Medical Corps (RAMC), serving to the end of World War I (WWI), each being awarded the Military Cross for gallantry. After WWI, they trained as radiologists and moved to St Leonards-on-Sea in West Sussex, taking up Consultant posts at the Royal East Sussex Hospital and the Municipal Hospital in Hastings, and the Eversfield Chest Hospital in St Leonards. In 1940 they rejoined the RAMC as radiologists, serving throughout World War II. They remained unmarried, devoted to each other, to their practice and to their loves of model engineering and flying, the latter nearly causing their deaths in an air crash in 1936. PMID- 17356732 TI - The Osler industry: insightful history or insipid hagiography? AB - The life and legacy of Sir William Osler (1849-1919) have been celebrated by nearly 1900 articles, 10 special issues of medical journals, several biographies, numerous lectures and orations, and regular meetings of 'Osler Societies' throughout the world. To what extent does this 'industry' reflect serious history as opposed to hagiography? The overarching purpose of this special issue of the Journal of Medical Biography is to present Osler as a real person from whom useful examples--both admirable and not so admirable--can be drawn for a 21st century readership. PMID- 17356733 TI - John Singer Sargent and the four doctors. PMID- 17356734 TI - William Osler's historical scholarship: a contradiction in terms? AB - For many it is difficult to grasp, let alone understand in any depth, the abundant nature of William Osler's (1849-1919) influence. Although knowing his name as a distinguished physician, few have more than a scant appreciation of his manifold contributions to medicine, and his example as the physician/historian and medical humanist par excellence. This essay considers Osler's scholarship as evidenced in his historical and biographical writings, and some lessons that we might learn from his endeavours. PMID- 17356735 TI - The Osler Societies: a qualitative and quantitative portrait. AB - Over 700 presentations have been given at the meetings of the American Osler Society (AOS) since its inception in 1970. Fully half of these have treated various aspects of Osler's personal and professional life. Many have dealt with Osler's specific contributions to an array of medical specialties. Other national/international Osler Societies including the Osler Club of London and the Japan Osler Society have treated similar topics but in different proportions historically. As the societies have matured, the foci of their talks have broadened from Osler and more bio-medical historical topics to include more of the contemporary ethical, ideological and socioeconomic issues facing the medical profession. Osler himself tended to speak more frequently on such topics in his later life. For Oslerians, Osler has had such a profound influence upon the history of medicine that, at least for them, to study Osler is to study the history of medicine. A description of the culture of the AOS meetings is ventured. PMID- 17356736 TI - Osler's McGill: medical education from 1870 to 1885. AB - In 1870 William Osler (1849-1919) switched from medical studies at the University of Toronto and finished his final two years at McGill University, graduating in 1872. After two years of study abroad, he returned to McGill's medical faculty where he taught for 10 years. This paper surveys the less well-known student environment of the time. It looks at faculty members and reforms to the curriculum at McGill that contributed to Osler's development as a doctor taking into account his own subsequent contributions as a member of faculty. PMID- 17356737 TI - Was Osler opposed to women becoming doctors? AB - In 1885 William Osler (1849-1919) expressed his opposition to women-only medical schools in Canada arguing there was no market for female practitioners. He believed women were not strong enough for clinical practice. He was unhappy that the Johns Hopkins University was forced to accept women when its Medical School opened in 1893. At Oxford he continued to express concern about the fitness of women for practice and suggested their best opportunities lay in a limited number of areas--pathology, institutions for women, the care of women and children in general practice, and in India and the missionary field. His views seemed to change during the First World War, when he helped to raise funds for the London School of Medicine for Women and supported Charles Sherrington's attempt to get women admitted to the Oxford Medical School. However, in his last year he was again concerned about the relatively poor quality of women physicians--but at least thought it unsurprising considering how badly they had been treated! PMID- 17356738 TI - The reserves of life: William Osler versus Almroth Wright. AB - William Osler's address, The Reserves of Life, was given to students at St Mary's Hospital Medical School in London in 1907. In the talk Osler likened a medical career to a race through London, pointing out that to be successful one had to have sufficient 'reserves' or staying powers. He also commented on several of his favourite topics and included some of his most memorable aphorisms. Almroth Wright was the colourful and controversial physician at St Mary's Hospital who described opsonins and was a strong advocate of vaccine therapy for bacterial infections. Wright was often critical of clinicians and scoffed at their crude methods. During the address to the St Mary's students, Osler abruptly departed from his theme to criticize Wright ('that Celtic Siren') and defend clinicians, emphasizing that the art and science of medicine were inseparable. Despite their differences, Osler and Wright maintained a cordial relationship. PMID- 17356739 TI - 'Tell Brother Regius...' Clifford Allbutt's correspondence with Archibald Malloch during Osler's final illness. AB - A very close friendship developed between Sir Clifford Allbutt (1836-1925) and Sir William Osler (1849-1919) after they became regius professors at the universities of Cambridge and Oxford, respectively. In 1919, Osler contracted influenza during the 1918-19 pandemic. The disease developed into serious pneumonia and empyema and was the cause of his death. One of his attending physicians in his final illness was Dr T Archibald Malloch (1887-1953) with whom Allbutt began to correspond. Allbutt's letters to Malloch are presented here. Allbutt was an exemplary physician. His handwriting, however, left much to be desired. Transcription of these letters was no mean feat. PMID- 17356740 TI - Osler and oriental medicine. PMID- 17356741 TI - Osler and the black corpuscles: profiles of three early students of phagocytosis. AB - The discovery of phagocytosis is associated indelibly with Elie Metchnikoff, who coined the term, but more than 30 persons had observed the phenomenon (or inferred its existence) before Metchnikoff came to dominate the field. Two of these early investigators were William Osler and George Miller Sternberg. Osler recognized carbon particles within the phagocytes of patients with miner's lung and carried out experiments in kittens. Sternberg only theorized about phagocytosis but, unlike Osler, bitterly contested Metchnikoff's priority of discovery. PMID- 17356742 TI - William Osler and appendicitis. AB - William Osler had cared for patients with 'typhlitis' and had seen perforations of the appendix in postmortem examinations before the day when he heard Reginald Heber Fitz proclaim that typhlitis was in fact disease of the appendix, that early surgery was indicated to treat perforation and that the process ought to be called 'appendicitis'. This paper examines the evolution of Osler's thoughts about appendicitis and documents his changing recommendations for treatment as presented in the eight editions of his text published during his lifetime. PMID- 17356743 TI - Osler's service: a view of the charts. AB - It has been asserted that William Osler (1849-1919) shaped the Medical Clinic of the Johns Hopkins Hospital 'to become a pre-eminent facility, first in patient care and later in medical education'. Osler's impact on medical education in the United States is beyond dispute, but few, if any, data support the assertion that patients at the Johns Hopkins Hospital fared better than those at similar hospitals during the late 19th century. Patient records were scanty and were seldom, if ever, signed by Osler or other senior professors. The numerous publications that arose from Osler's service suggest the data were derived not from the hospital charts, but rather from a parallel system of data collection designed mainly for research. Issues raised by this review of the charts on Osler's service reverberate in American medicine. PMID- 17356744 TI - William Osler's Study of the Act of Dying: an analysis of the original data. AB - Because of popular fears about death and dying, his personal interest in the subject and a lack of empirical data regarding the dying process, William Osler conducted a novel 'Study of the Act of Dying' of 486 patients at the Johns Hopkins Hospital between 1900 and 1904. Osler never wrote a manuscript describing the results of this study. However, in his lecture 'Science and Immortality' Osler mentioned the study briefly and reported that 104 patients (21%) experienced physical, mental or spiritual discomforts. He concluded that for most patients 'death was a sleep and a forgetting'. To better understand the results of Osler's study, the original data collection cards and a spreadsheet of the study data used by Osler were carefully examined. One hundred and eighty-six unique patients (38%) experienced discomforts, 79% higher than Osler reported in 'Science and Immortality'. Overall, 76 cards contained data discrepant with Osler's spreadsheet (McNemar's test, P<0.05). A number of factors, including haste, may account for the discrepant results. Nevertheless, the results shed light on the dying process during Osler's time. Furthermore, the results suggest that many dying patients during Osler's time experienced discomforts. PMID- 17356745 TI - 'Life in the tropics for Europeans', an unpublished lecture by William Osler. AB - An unpublished lecture by William Osler given in 1911 to young British administrators going to India gives glimpses of imperial history and travel medicine, and contains echoes of debates current at that time on a healthy tropical lifestyle and also the influence of race and climate on health. PMID- 17356746 TI - Osler's lost thesis. AB - William Osler's thesis was undertaken in 1871 to fulfil the graduation requirements of the McGill Faculty of Medicine. The thesis was based upon 20 autopsies and the preparation of gross and microscopic specimens. To the despair of historians, only a portion, the Introduction, was thought to have survived and part of which appeared in Cushing's biography. In the Osler Library is the final version of the Introduction together with parts of newly found earlier drafts and several incomplete autopsy reports and commentaries from the body of the thesis. Osler's early literary and classical erudition is clearly seen, and his philosophy of pathology as the foundation of clinical medicine strongly expressed. In addition, from a fragment of commentary on one of the postmortems, a venture into parasitology is seen representing what appears to be the first identification of the beef tapeworm in Canada. PMID- 17356747 TI - Oslerians and the Rolls Park portrait of William Harvey. PMID- 17356748 TI - Alternative fuel technologies. PMID- 17356749 TI - Nanometer scale carbon structures for charge-transfer systems and photovoltaic applications. AB - This article surveys and highlights the integration of nanometer scale carbon structures--in combination with chromophores that exhibit (i) significant absorption cross section throughout the visible part of the solar spectrum and (ii) good electron donating power--into novel electron donor-acceptor conjugates (i.e., covalent) and hybrids (i.e., non-covalent). The focus of this article is predominantly on performance features--charge-transfer and photovoltaic--of the most promising solar energy conversion systems. Besides documenting fundamental advantages as they emerge around nanometer scale carbon structures, critical evaluations of the most recent developments in the fields are provided. PMID- 17356750 TI - Thermodynamics of reversible gas adsorption on alkali-metal exchanged zeolites- the interplay of infrared spectroscopy and theoretical calculations. AB - Detailed understanding of weak solid-gas interactions giving rise to reversible gas adsorption on zeolites and related materials is relevant to both, fundamental studies on gas adsorption and potential improvement on a number of (adsorption based) technological processes. Combination of variable-temperature infrared spectroscopy with theoretical calculations constitutes a fruitful approach towards both of these aims. Such an approach is demonstrated here (mainly) by reviewing recent studies on hydrogen and carbon monoxide adsorption (at a low temperature) on alkali-metal exchanged ferrierite. However, the methodology discussed, which involves the interplay of experimental measurements and theoretical calculations at the periodic DFT level, should be equally valid for many other gas-solid systems. Specific aspects considered are the identification of gas adsorption complexes and thermodynamic studies related to standard adsorption enthalpy and entropy. PMID- 17356751 TI - Using first principles calculations to identify new destabilized metal hydride reactions for reversible hydrogen storage. AB - Hydrides of period 2 and 3 elements are promising candidates for hydrogen storage, but typically have heats of reaction that are too high to be of use for fuel cell vehicles. Recent experimental work has focused on destabilizing metal hydrides through mixing metal hydrides with other compounds. A very large number of possible destabilized metal hydride reaction schemes exist, but the thermodynamic data required to assess the enthalpies of these reactions are not available in many cases. We have used density functional theory calculations to predict the reaction enthalpies for more than 300 destabilization reactions that have not previously been reported. The large majority of these reactions are predicted not to be useful for reversible hydrogen storage, having calculated reaction enthalpies that are either too high or too low, and hence these reactions need not be investigated experimentally. Our calculations also identify multiple promising reactions that have large enough hydrogen storage capacities to be useful in practical applications and have reaction thermodynamics that appear to be suitable for use in fuel cell vehicles and are therefore promising candidates for experimental work. PMID- 17356752 TI - Dynamics of efficient electron-hole separation in TiO2 nanoparticles revealed by femtosecond transient absorption spectroscopy under the weak-excitation condition. AB - The transient absorption of nanocrystalline TiO(2) films in the visible and IR wavelength regions was measured under the weak-excitation condition, where the second-order electron-hole recombination process can be ignored. The intrinsic dynamics of the electron-hole pairs in the femtosecond to picosecond time range was elucidated. Surface-trapped electrons and surface-trapped holes were generated within approximately 200 fs (time resolution). Surface-trapped electrons, which gave an absorption peak at around 800 nm, and bulk electrons, which absorbed in the IR wavelength region, decayed with a 500-ps time constant due to relaxation into deep bulk trapping sites. It is already known that, after this relaxation, electrons and holes survive for microseconds. We interpreted these long lifetimes in terms of the prompt spatial charge separation of electrons in the bulk and holes at the surface. PMID- 17356753 TI - Catalytic partial oxidation of methane to synthesis gas over a ruthenium catalyst: the role of the oxidation state. AB - The catalytic partial oxidation of methane to synthesis gas over ruthenium catalysts was investigated by thermogravimetry coupled with infrared spectroscopy (TGA-FTIR) and in situ X-ray absorption spectroscopy (XAS). It was found that the oxidation state of the catalyst influences the product formation. On oxidized ruthenium sites, carbon dioxide was formed. The reduced catalyst yielded carbon monoxide as a product. The influence of the temperature was also investigated. At temperatures below the ignition point of the reaction, the catalyst was in an oxidized state. At temperatures above the ignition point, the catalyst was reduced. This was also confirmed by the in situ XAS spectroscopy. The results indicate that both a direct reaction mechanism as well as a combustion-reforming mechanism can occur. The importance of knowing the oxidation state of the surface is discussed and a method to determine it under reaction conditions is presented. PMID- 17356754 TI - Photoinduced charge separation in self-assembled cofacial pentamers of zinc 5,10,15,20-tetrakis(perylenediimide)porphyrin. AB - A bichromophoric electron donor-acceptor molecule composed of a zinc tetraphenylporphyrin (ZnTPP) surrounded by four perylene-3,4:9,10 bis(dicarboximide)(PDI) chromophores (ZnTPP-PDI(4)) was synthesized. The properties of this molecule were compared to a reference molecule having ZnTPP covalently bound to a single PDI (ZnTPP-PDI). In toluene, ZnTPP-PDI(4) self assembles into monodisperse aggregates of five molecules arranged in a columnar stack, (ZnTPP-PDI(4))(5). The monodisperse nature of this assembly contrasts sharply with previously reported ZnTPP-PDI(4) derivatives having 1,7-bis(3,5-di-t butylphenoxy) groups (ZnTPP-PPDI(4)). The size and structure of this assembly in solution was determined by small angle X-ray scattering (SAXS) using a high flux synchrotron X-ray source. The ZnTPP-PDI reference molecule does not aggregate. Femtosecond transient absorption spectroscopy shows that laser excitation of both ZnTPP-PDI and (ZnTPP-PDI(4))(5) results in quantitative formation of ZnTPP(+*) PDI(-*) radical ion pairs in a few picoseconds. The transient absorption spectra of (ZnTPP-PDI(4))(5) suggest that the PDI(-*) radicals interact strongly with adjacent PDI molecules within the columnar stack. Charge recombination occurs more slowly within (ZnTPP-PDI(4))(5)(tau= 4.8 ns) than it does in ZnTPP-PDI (tau= 3.0 ns) producing mostly ground state as well as a modest yield of the lowest triplet state of PDI ((3*)PDI). Formation of (3*)PDI occurs by rapid spin-orbit induced intersystem crossing (SO-ISC) directly from the singlet radical ion pair as evidenced by the electron spin polarization pattern exhibited by its time resolved electron paramagnetic resonance spectrum. PMID- 17356755 TI - Investigations of the ex situ ionic conductivities at 30 degrees C of metal cation-free quaternary ammonium alkaline anion-exchange membranes in static atmospheres of different relative humidities. AB - This article presents the first systematic study of the effect of Relative Humidity (RH) on the water content and hydroxide ion conductivity of quaternary ammonium-based Alkaline Anion-Exchange Membranes (AAEMs). These AAEMs have been developed specifically for application in alkaline membrane fuel cells, where conductivities of >0.01 S cm(-1) are mandatory. When fully hydrated, an ETFE based radiation-grafted AAEM exhibited a hydroxide ion conductivity of 0.030 +/- 0.005 S cm(-1) at 30 degrees C without additional incorporation of metal hydroxide salts; this is contrary to the previous wisdom that anion-exchange membranes are very low in ionic conductivity and represents a significant breakthrough for metal-cation-free alkaline ionomers. Desirably, this AAEM also showed increased dimensional stability on full hydration compared to a Nafion-115 proton-exchange membrane; this dimensional stability is further improved (with no concomitant reduction in ionic conductivity) with a commercial AAEM of similar density but containing additional cross-linking. However, all of the AAEMs evaluated in this study demonstrated unacceptably low conductivities when the humidity of the surrounding static atmospheres was reduced (RH = 33-91%); this highlights the requirement for continued AAEM development for operation in H(2)/air fuel cells with low humidity gas supplies. Preliminary investigations indicate that the activation energies for OH(-) conduction in these quaternary ammonium-based solid polymer electrolytes are typically 2-3 times higher than for H(+) conduction in acidic Nafion-115 at all humidities. PMID- 17356756 TI - Efficient photocatalytic hydrogen evolution without an electron mediator using a simple electron donor-acceptor dyad. AB - A highly efficient photocatalytic hydrogen evolution system without an electron mediator such as methyl viologen (MV(2+)) has been constructed using 9-mesityl-10 methylacridinium ion (Acr(+)-Mes), poly(N-vinyl-2-pyrrolidone)-protected platinum nanoclusters (Pt-PVP) and NADH (beta-nicotinamide adenine dinucleotide, reduced form) as the photocatalyst, hydrogen evolution catalyst and electron donor, respectively. The photocatalyst (Acr(+)-Mes) undergoes photoinduced electron transfer (ET) from the Mes moiety to the singlet excited state of the Acr(+) moiety to produce an extremely long-lived ET state, which is capable of oxidizing NADH and reducing Pt-PVP, leading to efficient hydrogen evolution. The hydrogen evolution efficiency is 300 times higher than that in the presence of MV(2+) because of the much faster reduction rate of Pt-PVP by Acr(*)-Mes compared with that by MV(*+). When the electron donor (NADH) is replaced by ethanol in the presence of an alcohol dehydrogenase (ADH), NADH is regenerated during the photocatalytic hydrogen evolution. PMID- 17356757 TI - Electronic structure calculations on lithium battery electrolyte salts. AB - New lithium salts for non-aqueous liquid, gel and polymeric electrolytes are crucial due to the limiting role of the electrolyte in modern lithium batteries. The solvation of any lithium salt to form an electrolyte solution ultimately depends on the strength of the cation-solvent vs. the cation-anion interaction. Here, the latter is probed via HF, B3LYP and G3 theory gas-phase calculations for the dissociation reaction: LiX <--> Li(+) + X(-). Furthermore, a continuum solvation method (C-PCM) has been applied to mimic solvent effects. Anion volumes were also calculated to facilitate a discussion on ion conductivities and cation transport numbers. Judging from the present results, synthesis efforts should target heterocyclic anions with a size of ca. 150 A(3) molecule(-1) to render new highly dissociative lithium salts that result in electrolytes with high cation transport numbers. PMID- 17356758 TI - Functional anion concept: effect of fluorine anion on hydrogen storage of sodium alanate. AB - Doping NaAlH(4) with Ti-catalyst has produced a promising hydrogen storage system that can be reversibly operated at moderate temperature conditions. Of the various dopant precursors, TiCl(3) was well recognized due to its pronounced catalytic effect on the reversible dehydrogenation processes of sodium aluminium hydrides. Quite recently we experimentally found that TiF(3) was even better than TiCl(3) in terms of the critical hydrogen storage properties of the doped hydrides, in particular the dehydriding performance at Na(3)AlH(6)/NaH + Al step at moderate temperature. We present here the DFT calculation results of the TiF(3) or TiCl(3) doped Na(3)AlH(6). Our computational studies have demonstrated that F(-) and Cl(-) anions differ substantially from each other with regard to the state and function in the doped sodium aluminium hydride. In great contrast to the case of chloride doping where Cl(-) anion constitutes the "dead weight" NaCl, the fluoride doping results in a substitution of H(-) by F(-) anion in the hydride lattice and accordingly, a favorable thermodynamics adjustment. These results well explain the observed dehydriding performance associated with TiF(3)/TiCl(3)-doping. More significantly, the coupled computational and experimental efforts allow us to put forward a "functional anion" concept. This renews the current mechanism understanding in the catalytically enhanced sodium alanate. PMID- 17356759 TI - Heterostructured magnetic nanoparticles: their versatility and high performance capabilities. AB - Magnetic nanoparticles exhibit unique nanoscale properties and their utilization for various magnetic systems is of significant interest. Especially, heterostructured magnetic nanoparticles are emerging as next-generation materials due to their synergistically enhanced magnetism and potential multifunctionalities. Herein, we overview the recent advances in the development of magnetic nanoparticles with a focus on multicomponent heterostructured nanoparticles including alloys, core-shells, and binary superlattices synthesized via nonhydrolytic methods. Their multifunctionalites and high performance capabilities are demonstrated for applications in high density magnetic storages, chemical catalysis, and biomedical separation and diagnostics. PMID- 17356760 TI - Parameters for selective colorimetric sensing of mercury(II) in aqueous solutions using mercaptopropionic acid-modified gold nanoparticles. AB - We unveil a new homogeneous assay-using mercaptopropionic acid-modified Au nanoparticles in the presence of 2,6-pyridinedicarboxylic acid for the highly selective and sensitive detection of Hg(2+) ions. PMID- 17356761 TI - Quantitative detection of protein expression in single cells using droplet microfluidics. AB - We demonstrate that single cells can be controllably compartmentalized within aqueous microdroplets; using such an approach we perform high-throughput screening by detecting the expression of a fluorescent protein in individual cells with simultaneous measurement of droplet size and cell occupancy. PMID- 17356762 TI - Effect of peracetylation on the conformation of gamma-cyclodextrin. AB - The well-known, fourfold symmetry of the gamma-CD molecule in its solid inclusion complexes is lost on peracetylation, which yields a highly distorted host molecule in which self-inclusion of acetyl residues divides the macrocyclic cavity into two distinct sub-cavities that accommodate solvent molecules. PMID- 17356764 TI - Vancomycin architecture dependence on the capture efficiency of antibody-modified microbeads by magnetic nanoparticles. AB - We show that the ability to control the architecture/orientation of vancomycin on the surface of magnetic nanoparticles has a drastic effect on the ability of the nanoparticles to magnetically confine vancomycin-antibody modified polystyrene microbeads. PMID- 17356763 TI - First hypervalent iodine(III)-catalyzed C-N bond forming reaction: catalytic spirocyclization of amides to N-fused spirolactams. AB - A protic solvent, 2,2,2-trifluoroethanol (CF(3)CH(2)OH), was successfully introduced into hypervalent iodine(III)-involved catalytic cycles as an effective solvent, and the first iodoarene-catalyzed intramolecular carbon-nitrogen bond forming reaction was achieved under strong acid-free and mild conditions. PMID- 17356765 TI - A dizinc complex for selective fluorescence sensing of uridine and uridine containing dinucleotides. AB - A dizinc complex with a polyamine macrocycle is able to selectively bind and sense uridine (U) as well as the uridine-containing ribodinucleotides U(3'-5')pU and U(3'-5')pA, thanks to an exciplex emission arising from a pi-stacked complex involving the dipyridine unit and Zn(II)-bound uridine moieties. PMID- 17356766 TI - Pure silica ITQ-32 zeolite allows separation of linear olefins from paraffins. AB - ITQ-32 is able to separate propene from propane and represents a clear improvement with respect to previous zeolites in achieving the separation of trans-2-butene and 1-butene from the C(4) fraction using only one zeolite. PMID- 17356767 TI - Direct-type catalytic Mannich reactions of amides with imines. AB - Direct-type catalytic Mannich reactions of amides with imines proceeded smoothly using barium phenoxide as a catalyst to afford the desired adducts in high yields with high anti selectivities. PMID- 17356768 TI - A FRET approach to phosgene detection. AB - A FRET approach towards potential detection of phosgene is presented, which is based on a selective chemical reaction between phosgene (or triphosgene as a simulant) and donor and acceptor fluorophores. PMID- 17356769 TI - TLC plates as a convenient platform for solvent-free reactions. AB - Solvent-free oxidative couplings of naphthols have been optimized by co-spotting catalysts and substrates directly on silica TLC plates and heating, followed by chromatography, staining, and qualitative visualization. PMID- 17356770 TI - Effective and efficient photoluminescence of salicylate-ligating terbium(III) clusters stabilized by multiple phenyl-phenyl interactions. AB - A luminescent nonanuclear terbium(III) hydroxo cluster, Tb(9)(Hesa)(16)(mu OH)(10)(NO(3)) (Hesa: hexyl salicylate), stabilized by unique two-way phenyl ring interactions, pi-pi stackings (d = 3.482-3.599 A) and C-H-pi interactions (d = 2.75-3.03 A) between adjacent pairs of salicylates, was structurally characterized based on X-ray analysis, and the favourable absorption change and efficient photoluminescent characteristic were rationalized as being due to J type pi-pi stackings, which are dramatically enhanced by hexyl groups in hexyl salicylate ligands. PMID- 17356771 TI - Oligomeric rod-disc nematic liquid crystals. AB - Six new oligomeric nematic liquid crystals are reported consisting of a triphenylene-based core attached to which are six 4-cyanobiphenyl units via flexible alkyl spacers. PMID- 17356772 TI - Polymeric model systems for flavoenzyme activity: towards synthetic flavoenzymes. AB - We report the synthesis of a water-soluble flavin polymer using ATRP, whereby the oligoethylene glycol backbone provides both a local hydrophobic environment and redox tuning of the flavin moiety typical of flavoenzyme prototypes. PMID- 17356773 TI - A novel quantitative proteomics reagent based on soluble nanopolymers. AB - Bi-functionalized dendrimers leads to highly efficient quantitative proteomics and the determination of protease activities in snake venoms. PMID- 17356774 TI - Molecular electronics: connection across nano-sized electrode gaps. AB - Prefabricated nano-scale structures in which gold electrodes are separated by an insulating core permit self-assembly of a single string "molecular necklace" around its circumference; these devices require no further invasive metal deposition following molecular insertion and exhibit symmetrical current-voltage (I-V) curves that mimic those of self-assembled films on planar substrates. PMID- 17356775 TI - Seeking tetrameric transition metal phosphonate with a D4R core and organising it into a 3-D supramolecular assembly. AB - The first cubic zinc phosphonate [tBuPO(3)Zn(2-apy)](4) (1) whose core resembles the D4R SBU of zeolites, has been synthesised from a reaction between zinc acetate, tert-butylphosphonic acid and 2-aminopyridine at room temperature; the X ray structure determination reveals that the molecules of , which crystallise in the tetragonal I4(1)/a space group with crystallographically imposed 4 symmetry, form a 3-D supramolecular assembly aided by N-H...O hydrogen bonding. PMID- 17356776 TI - Metal-catalyzed radical polyaddition as a novel polymer synthetic route. AB - A new class of polymerizations was developed via metal-catalyzed C-C bond forming radical polyaddition; the monomers were designed to have a reactive C-Cl bond, which can be activated by the metal catalysts to generate a carbon radical species, along with a C=C double bond, to which the carbon radical generated from another molecule adds to form a C-C backbone polymer with an inactive C-Cl pendant. PMID- 17356777 TI - Microsystem controlled cationic polymerization of vinyl ethers initiated by CF3SO3H. AB - Practical cationic polymerization and block-copolymerization of vinyl ethers have been achieved at -25 degrees C by using CF(3)SO(3)H initiator in microsystems with high level of molecular weight distribution control. PMID- 17356778 TI - Hydrophobic, organically-modified silica gels enhance the secondary structure of encapsulated apomyoglobin. AB - Insertion of hydrophobic groups in a silica matrix, by addition of propyl- or trifluoropropyltrimethoxysilane, leads to a surprising increase in the helical content of apomyoglobin following encapsulation by the sol-gel technique. PMID- 17356779 TI - Viral MRI contrast agents: coordination of Gd by native virions and attachment of Gd complexes by azide-alkyne cycloaddition. AB - Icosahedral virus particles decorated with a Gd(DOTA) analogue by Cu-mediated azide-alkyne cycloaddition (CuAAC) and/or with Gd(3+) ions by coordination to the viral nucleoprotein show increased T(1) relaxivity relative to free Gd(DOTA) complexes in solution. PMID- 17356780 TI - Fabrication of well-defined water-soluble core/shell heteronanostructures through the SiO2 spacer. AB - A generalized approach for the fabrication of core/shell heteronanostructures through a simple chemical bath deposition method assisted by the bridging of SiO(2) spacer has been developed and a slow heterogeneous nucleation mechanism identified as the key to the success of this method. PMID- 17356781 TI - Highly unusual conversion of 1-alkyl-2-(bromomethyl)aziridines into 1-alkyl-2-(N alkyl-N-ethylaminomethyl)aziridines using methyllithium. AB - 1-alkyl-2-(bromomethyl)aziridines were transformed into 1-alkyl-2-(N-alkyl-N ethylaminomethyl)aziridines upon treatment with 2-3 equiv. of methyllithium in THF or Et(2)O; the peculiarity in this transformation comprises the presence of an N-ethyl group in the end-products as well as the total number of carbon atoms, resulting from a highly unusual reaction course with a novel S(N)2'-type substitution at the aziridine moiety and liberation of acetylene from an intermediate vinylamine as the key reaction steps. PMID- 17356782 TI - Fine tuning of the orifice size of an open-cage fullerene by placing selenium in the rim: insertion/release of molecular hydrogen. AB - A newly synthesized open-cage fullerene containing selenium in the rim of the 13 membered-ring orifice allows milder conditions for hydrogen insertion, and the rate for hydrogen release is ca. three times faster than its sulfur analogue. PMID- 17356783 TI - Reaction of imines with N-iodosuccinimide (NIS): unexpected formation of stable 1 : 1 complexes. AB - Imines react with N-iodosuccinimide (NIS) to afford unexpected 1 : 1 complexes and the structure of one of these was determined by single-crystal X-ray diffraction; the reaction seems to be very general for substituted cyclic imines with solid stable complexes obtained in high yields; this is the first reported example of a halogen bonding interaction involving the C=N bond and NIS. PMID- 17356784 TI - Dynamic kinetic resolution of 2-oxo-3-aryl-succinates by organocatalyzed aldolization. AB - The dynamic kinetic resolution of 2-oxo-3-arylsuccinates was achieved vial proline-catalyzed addition of acetone in acetonitrile at room temperature, providing the desired adduct in good yield with up to 87 : 13 dr and high ee up to 99%. PMID- 17356785 TI - Inhalation therapy: an historical review. AB - SUMMARY: Inhalation has been employed as a method for delivering medications for more than two thousand years, and the benefits of delivering medication directly to the affected site - the lungs - have been understood for more than two hundred years. At the beginning of the Industrial Revolution, physicians were inventing therapies and experimenting with ideas for devices: it was a time of great creativity. However, by the end of the period the scientist and the regulated pharmaceutical industry had emerged and the role of the physician had been constrained. Few of the devices invented then remain in use today, but many of the principles used are still embodied in modern devices. This review traces the developments produced by the early pioneers who applied their creative thoughts to inhalation therapy, and examines how inhaled drug delivery has progressed. The devices pictured are from www.inhalatorium.com, an online museum of inhalation technologies. PMID- 17356786 TI - The use of a modification of the Patient Enablement Instrument in asthma. AB - AIM: To ascertain if the Patient Enablement Instrument (PEI) could be adapted for use in asthma management, and to use it to evaluate "enablement" in patients with asthma randomised to either a fixed or adjustable medication dosing regime. METHODS: The original Patient Enablement Instrument was modified by making a minor change to the opening statement. 228 adults with asthma from 72 UK general practices were recruited to the study. The internal and external consistencies of the modified PEI were assessed. Individual scores were compared across treatment groups. RESULTS: The modified PEI had high internal consistency. There was a significant correlation between modified PEI total score and change in Mini Asthma Quality of Life Questionnaire. A significantly greater proportion of patients using adjustable medication dosing had a clinically relevant treatment benefit. CONCLUSIONS: The Patient Enablement Instrument can be used to measure "enablement" in asthma. PMID- 17356787 TI - Suspected lung cancer: its initial management and staging. AB - Lung cancer has traditionally been viewed as being difficult to treat and generally associated with a poor outcome. With new advances in technology and medicine in general, the public has come to expect a better prognosis from lung cancer. Once a patient has been referred with suspected lung cancer, it is important to confirm the diagnosis and to stage the cancer; in this way, one can ascertain whether or not the cancer is potentially operable. By providing definitive surgery, the aim is to cure the patient of cancer. The role of staging extends beyond that of merely directing appropriate therapy or determining the patient pathway (be it supportive, palliative or curative); it also has prognostic implications including the likelihood of survival from lung cancer. PMID- 17356788 TI - Apolipoprotein B binds ferritin by hemin-mediated binding: evidence of direct binding of apolipoprotein B and ferritin to hemin. AB - Apolipoprotein B (apoB) is known to be a ferritin-binding protein. Here we show that apoB binds to ferritin through hemin-mediated binding. Human apoB bound to bovine spleen, horse spleen, and canine liver ferritins, but did not bind to bovine apoferritin, even after incorporation of iron into it. Incubation of apoferritin with hemin resulted in apoB binding with apoferritin at the same level as with holoferritin. In contrast, hemin inhibited binding of apoB to ferritin. Bovine spleen apoferritin bound biotinylated hemin, and hemin inhibited the binding between the apoferritin and biotinylated hemin, suggesting that ferritin binds hemin directly. ApoB and LDL containing apoB bound biotinylated hemin, and their bindings were also inhibited by hemin, but not protoporphyrin IX. These data demonstrate that binding of apoB to ferritin is mediated through ferritin's binding to hemin, and also that apoB binds hemin directly. PMID- 17356789 TI - In vitro biocontrol analysis of Alternaria alternata (Fr.) Keissler under different environmental conditions. AB - The species Trichoderma harzianum was analyzed as possible biocontrol agent of Alternaria alternata under different environmental conditions (water activity and temperature). The strains were analyzed macroscopically to obtain the Index of Dominance. The analysis was completed using two microscopic techniques. T. harzianum showed dominance on contact over A. alternata at all testing temperatures and water activities tested except at 0.95 a(w) and 15 degrees C, at which T. harzianum inhibited A. alternata at a distance. Biocontrol was governed by different mechanisms such as competition for space and nutrients, mycoparasitism, and possible antibiosis. Temperature and water activity significantly influenced fungal growth rate. PMID- 17356790 TI - In vitro activity of eugenol against Candida albicans biofilms. AB - Most manifestations of candidiasis are associated with biofilm formation occurring on the surfaces of host tissues and medical devices. Candida albicans is the most frequently isolated causative pathogen of candidiasis, and the biofilms display significantly increased levels of resistance to the conventional antifungal agents. Eugenol, the major phenolic component of clove essential oil, possesses potent antifungal activity. The aim of this study was to investigate the effects of eugenol on preformed biofilms, adherent cells, subsequent biofilm formation and cell morphogenesis of C. albicans. Eugenol displayed in vitro activity against C. albicans cells within biofilms, when MIC(50) for sessile cells was 500 mg/L. C. albicans adherent cell populations (after 0, 1, 2 and 4 h of adherence) were treated with various concentrations of eugenol (0, 20, 200 and 2,000 mg/L). The extent of subsequent biofilm formation were then assessed with the tetrazolium salt reduction assay. Effect of eugenol on morphogenesis of C. albicans cells was observed by scanning electron microscopy (SEM). The results indicated that the effect of eugenol on adherent cells and subsequent biofilm formation was dependent on the initial adherence time and the concentration of this compound, and that eugenol can inhibit filamentous growth of C. albicans cells. In addition, using human erythrocytes, eugenol showed low hemolytic activity. These results indicated that eugenol displayed potent activity against C. albicans biofilms in vitro with low cytotoxicity and therefore has potential therapeutic implication for biofilm-associated candidal infections. PMID- 17356791 TI - Degradation of keratinous materials by the plant pathogenic fungus Myrothecium verrucaria. AB - In this paper it is described for the first time the capability of Myrothecium verrucaria to grow in submerged and solid state cultures using poultry feathers as the only substrate. The fungus produced a protease with an unusual keratinolytic activity among plant pathogenic fungi. Its crude protease hydrolyzed keratinous substrates at pH 9.0 and 40 degrees C in the following order: poultry feather keratin > sheep wool keratin > human nail keratin > human hair keratin. Protease activity was highly sensitive to phenylmethyl sulphonyl fluoride (PMSF) indicating that the enzyme belonged to the serine protease family. PMID- 17356792 TI - Protection induced in BALB/c mice by the high-molecular-mass (hMM) fraction of Paracoccidioides brasiliensis. AB - Paracoccidioidomycosis (PCM) is a granulomatous disease caused by a dimorphic fungus, Paracoccidioides brasiliensis. The present study investigated the protective activity of the P. brasiliensis high-molecular-mass (hMM) fraction (approximately 380 kDa) in experimental murine PCM. In the first step, lymphocyte proliferation and production of IFNgamma (but not IL-4) were observed in "in vitro" spleen cells (from female BALB/c mice infected (i.v.) with P. brasiliensis) that were stimulated with hMM fractions. In the second step, female BALB/c mice were previously immunized (s.c.) with hMM fraction (25 microg/protein = F-25 and 50 microg/protein = F-50), and the colony-forming units (CFU) of the lung and spleen, the histopathological characteristics of the granulomatous lesions, and plasmatic gp43 soluble antigens and anti-hMM IgG levels were analyzed at 28 and 56 days after infection. The lung and liver CFU were lower in mice previously immunized with the hMM fraction (P < 0.05). The granulomatous lesions revealed a greater degree of compaction and organization, with no dissemination of the fungus to other organs. Lower soluble antigen levels (P < 0.05) and higher IgG anti-hMM fraction (P < 0.05) were observed in immunized groups. The results for CFU, histopathology and antigenemia suggest that the hMM fraction has a protective effect in experimental paracoccidioidomycosis in BALB/c mice. PMID- 17356793 TI - Asymmetric overlap extension PCR method bypassing intermediate purification and the amplification of wild-type template in site-directed mutagenesis. AB - By combining asymmetric PCR and overlap extension, we developed a novel asymmetric overlap extension PCR (AOE-PCR) method for site-directed mutagenesis which bypassed the need for intermediate purification and excluded the amplification of a wild-type template. This method was used to introduce single base mutations into a small GTPase gene from cotton and to simultaneously introduce two mutations just by repeating this method using the first round AOE PCR products as template. Our results suggested that the AOE-PCR method represents a valuable improvement of the original overlap extension PCR for site directed mutagenesis. PMID- 17356794 TI - Association of common polymorphisms in inflammatory genes with risk of developing cancers of the upper aerodigestive tract. AB - OBJECTIVES: The purpose of this study was to investigate the role of polymorphisms of genes involved in inflammation in the risk of cancers of the upper aerodigestive tract (UADT). METHODS: We have evaluated the role of polymorphisms in key genes related to inflammation, namely IL1B (rs1143627), COX2/PTGS2 (rs5275), and IL8 (rs4073) in a large case-control study comprising 811 UADT cancer cases and 1,083 controls. RESULTS: An association was observed for squamous cell carcinoma of the pharynx for a polymorphism in the promoter of the IL1B gene, with an OR of 2.39 (95% CI = 1.19-4.81) for the homozygotes for the minor allele A promoter polymorphism of IL8 was associated with decreased risk of laryngeal cancer, with an OR of 0.70 (95% CI = 0.50-0.98) for carriers of the minor allele. CONCLUSIONS: To our knowledge, this is the first report on the role of these polymorphisms with respect to UADT carcinogenesis. Our results suggest that inflammation-related polymorphisms play a role, albeit minor, in the risk of developing cancers of the upper aerodigestive tract. PMID- 17356795 TI - Relationship between diet and anticoagulant response to warfarin: a factor analysis. AB - BACKGROUND: Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin. AIM OF THE STUDY: To determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular disease. METHODS: Recent and usual food intakes were assessed in 115 patients receiving warfarin; and corresponding plasma phylloquinone (vitamin K(1)), serum triglyceride concentrations, prothrombin time (PT), and International Normalized Ratio (INR) were determined. A factor analysis was used to examine the association of specific foods and biochemical variables with anticoagulant data. RESULTS: Mean age was 59 +/- 15 years. Inadequate anticoagulation, defined as values of INR 2 or 3, was found in 48% of the patients. Soybean oil and kidney beans were the primary food sources of phylloquinone intake. Factor analysis yielded four separate factors, explaining 56.4% of the total variance in the data set. The factor analysis revealed that intakes of kidney beans and soybean oil, 24-h recall of phylloquinone intake, PT and INR loaded significantly on factor 1. Triglycerides, PT, INR, plasma phylloquinone, and duration of anticoagulation therapy loaded on factor 3. CONCLUSIONS: Fluctuations in phylloquinone intake, particularly from kidney beans, and plasma phylloquinone concentrations were associated with variation in measures of anticoagulation (PT and INR) in a Brazilian group of patients with vascular disease. PMID- 17356796 TI - Flavonoids inhibit the formation of the cross-linking AGE pentosidine in collagen incubated with glucose, according to their structure. AB - BACKGROUND: Glycoxidation of collagens contributes to development of vascular complications in diabetes. AIM OF THE STUDY: Since flavonoids are potent antioxidants present in vegetal foods, it was interesting to examine their effect on the formation of a cross-linking advanced glycation endproduct, pentosidine, in collagens. METHODS: Collagen was incubated with glucose (250 mM), in the presence of different flavonoids. Pentosidine was measured by HPLC, hydroxyproline colorimetrically. RESULTS: Monomeric flavonoids (25 and 250 microM) markedly reduced pentosidine/hydroxyproline values in a concentration- and structure-dependent manner. In decreasing order of their specific inhibitory activity, they rank as follows: myricetin > or = quercetin > rutin > (+)catechin > kaempferol. Thus 3'-OH or 4-oxo + Delta(2-3) increase the inhibitory activity; conjugation by Rha-Glc on 3-OH decreases it. Procyanidin oligomers from grape seed were more active than pine bark procyanidin oligomers: this may be related to the galloyl residues present in grape seed oligomers only. Procyanidin oligomers are known to be cleaved into monomers in the gastric milieu and monomeric flavonoids to be absorbed and recovered at micromolar concentrations (with a long plasmatic half-life) in extracellular fluids, in contact with collagens. CONCLUSION: Flavonoids are very potent inhibitors of pentosidine formation in collagens. They are active at micromolar concentrations; these might be achieved in plasma of diabetic patients after oral intake of natural flavonoids. PMID- 17356797 TI - Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery. AB - OBJECTIVE: Nitric oxide (NO) inhibits thrombus formation, vascular contraction, and smooth muscle cell proliferation. We investigated whether NO release is enhanced after endothelial NO synthase (eNOS) gene transfer in atherosclerotic human carotid artery ex vivo. METHODS AND RESULTS: Western blotting and immunohistochemistry revealed that transduction enhanced eNOS expression; however, neither nitrite production nor NO release measured by porphyrinic microsensor was altered. In contrast, transduction enhanced NO production in non atherosclerotic rat aorta and human internal mammary artery. In transduced carotid artery, calcium-dependent eNOS activity was minimal and did not differ from control conditions. Vascular tetrahydrobiopterin concentrations did not differ between the experimental groups. Treatment of transduced carotid artery with FAD, FMN, NADPH, L-arginine, and either sepiapterin or tetrahydrobiopterin did not alter NO release. Superoxide formation was similar in transduced carotid artery and control. Treatment of transduced carotid artery with superoxide dismutase (SOD), PEG-SOD, PEG-catalase did not affect NO release. CONCLUSIONS: eNOS transduction in atherosclerotic human carotid artery results in high expression without any measurable activity of the recombinant protein. The defect in the atherosclerotic vessels is neither caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty is performed in atherosclerotic arteries,eNOS gene therapy is unlikely to provide clinical benefit. PMID- 17356798 TI - Can community-dwelling women reliably identify infected urine? AB - The purpose of this study was to evaluate whether community-dwelling women can reliably identify infected urine samples. A convenience sample of 25 women judged six urine samples. Of these, two were normal, two contained culture-proven infections, and two were intentionally abnormal because of ingestion of asparagus or vitamins. The women decided if each sample was infected based on its color, clarity, and odor. For the two normal samples, 56 and 96% women correctly identified them. Of the two samples positive for infection, women were correct 80 and 100% of the time. Of the two samples designed to be abnormal, women were correct in 92 and 64% of their evaluations. Using the 150 total evaluations of urine samples, the sensitivity was 90%, and the specificity was 77%. Based on this small sample, community-dwelling women can detect infected samples of urine. However, women should still be screened for factors that might have distorted normal urine. PMID- 17356799 TI - The risk of anal incontinence in obese women. AB - The objectives of this study was to estimate the risk of anal incontinence in morbidly obese women and to identify risk factors associated with anal incontinence in an obese population sample. A case-control study based on the registry of a university hospital obesity unit. A consecutive sample of women with body mass index > or = 35 (obesity class II) was randomly matched by age, gender and residential county to control subjects using the computerised Register of the Total Population. Data were collected by a self-reported postal survey including detailed questions on medical and obstetrical history, obesity history, socioeconomic indices, life style factors and the validated Cleveland Clinic Incontinence Score. The questionnaire was returned by 131/179 (73%) of the cases and 453/892 (51%) of the control subjects. Compared to the control group, obese women reported a significantly increased defecation frequency (p < 0.001), inability to discriminate between flatus and faeces (p < 0.001) and flatus incontinence (p < 0.001). Compared with non-obese women, the adjusted odds ratio (OR) for flatus incontinence in morbidly obese women was 1.5 [95% confidence interval (CI) 1.1-4.1]. A history of obstetric sphincter injury was independently associated with an increased risk of flatus incontinence (OR, 4.3; 95% CI, 2.0 9.2) and incontinence of loose stools (OR, 6.6; 95% CI, 1.4-31.4). Other medical and life style interactions did not remain at significant levels in an adjusted multivariable analysis. Obese women are at increased risk for mild to moderate flatus incontinence. PMID- 17356800 TI - Hydrodynamic effects in bicontinuous microemulsions measured by inelastic neutron scattering. AB - The dynamical properties of bicontinuous microemulsions have been studied with neutron spin echo spectroscopy around length scales corresponding to the correlation peak q(0). Comparison of samples with different contrasts for neutrons shed light on the two modes dominated either by variation of the oil/water difference or surfactant concentration in the hydrodynamic regime. The results have been compared to theoretical predictions of the relaxation rates of bicontinuous microemulsions by Nonomura and Ohta [M. Nonomura, T. Ohta, J. Chem. Phys. 110, 7516 (1999)]. The influence of modification of the surfactant layer bending constants in the microemulsion by addition of homopolymers (polyethylenepropylene: PEP(X) and polyethyleneoxide: PEO(X), X=5 kg/mol), dissolved in the oil phase and water, has been investigated. PMID- 17356801 TI - Effect of high electric fields on the nematic to isotropic transition in a material exhibiting large negative dielectric anisotropy. AB - We report the experimental high electric field phase diagram of a nematic liquid crystal which exhibits a large negative dielectric anisotropy. We measure simultaneously the birefringence (Deltan) and the dielectric constant (epsilon( perpendicular)) at various applied fields as functions of the local temperature of an aligned sample. We also measure the higher harmonics of the electrical response of the medium. The following experimental results are noted: (i) enhancement of orientational order parameter S in the nematic phase due to both the Kerr effect and quenching of director fluctuations; (ii) enhancement in the paranematic to nematic transition temperature (T(PN)) with field; (iii) divergence of the order parameter susceptibility beyond the tricritical point as measured by third harmonic electrical signal; (iv) a small second harmonic electrical signal which also diverges near T(PN), indicating the presence of polarised domains. Our measurements show that DeltaT(PN)(= T(PN)(E)-T(NI)(0)) varies linearly with |E| whereas the Landau de Gennes theory predicts a dependence on E(2). It is argued that the quenching of director fluctuations by the field makes the dominant contribution to all the observations, including the thermodynamics of the transition. PMID- 17356802 TI - New analysis of a rat feeding study with a genetically modified maize reveals signs of hepatorenal toxicity. AB - Health risk assessment of genetically modified organisms (GMOs) cultivated for food or feed is under debate throughout the world, and very little data have been published on mid- or long-term toxicological studies with mammals. One of these studies performed under the responsibility of Monsanto Company with a transgenic corn MON863 has been subjected to questions from regulatory reviewers in Europe, where it was finally approved in 2005. This necessitated a new assessment of kidney pathological findings, and the results remained controversial. An Appeal Court action in Germany (Munster) allowed public access in June 2005 to all the crude data from this 90-day rat-feeding study. We independently re-analyzed these data. Appropriate statistics were added, such as a multivariate analysis of the growth curves, and for biochemical parameters comparisons between GMO-treated rats and the controls fed with an equivalent normal diet, and separately with six reference diets with different compositions. We observed that after the consumption of MON863, rats showed slight but dose-related significant variations in growth for both sexes, resulting in 3.3% decrease in weight for males and 3.7% increase for females. Chemistry measurements reveal signs of hepatorenal toxicity, marked also by differential sensitivities in males and females. Triglycerides increased by 24-40% in females (either at week 14, dose 11% or at week 5, dose 33%, respectively); urine phosphorus and sodium excretions diminished in males by 31-35% (week 14, dose 33%) for the most important results significantly linked to the treatment in comparison to seven diets tested. Longer experiments are essential in order to indicate the real nature and extent of the possible pathology; with the present data it cannot be concluded that GM corn MON863 is a safe product. PMID- 17356803 TI - Detectability of regional lung ventilation with flat-panel detector-based dynamic radiography. AB - This study was performed to investigate the ability of breathing chest radiography using flat-panel detector (FPD) to quantify relative local ventilation. Dynamic chest radiographs during respiration were obtained using a modified FPD system. Imaging was performed in three different positions, ie, standing and right and left decubitus positions, to change the distribution of local ventilation. We measured the average pixel value in the local lung area. Subsequently, the interframe differences, as well as difference values between maximum inspiratory and expiratory phases, were calculated. The results were visualized as images in the form of a color display to show more or less x-ray translucency. Temporal changes and spatial distribution of the results were then compared to lung physiology. In the results, the average pixel value in each lung was associated with respiratory phase. In all positions, respiratory changes of pixel value in the lower area were greater than those in the upper area (P < 0.01), which was the same tendency as the regional differences in ventilation determined by respiratory physiology. In addition, in the decubitus position, it was observed that areas with large respiratory changes in pixel value moved up in the vertical direction during expiration, which was considered to be airway closure. In conclusion, breathing chest radiography using FPD was shown to be capable of quantifying relative ventilation in local lung area and detecting regional differences in ventilation and timing of airway closure. This method is expected to be useful as a new diagnostic imaging modality for evaluating relative local ventilation. PMID- 17356804 TI - Impairment of the metastatic activity of melanoma cells by transglutaminase catalyzed incorporation of polyamines into laminin and Matrigel. AB - Previously published evidences highlighted the effect of transglutaminase (TG, EC 2.3.2.13) activation on the reduction of the in vitro adhesive and invasive behaviour of murine B16-F10 melanoma cells, as well as in vivo. Here, we investigated the influence of spermidine (SPD) incorporation by TG into basement membrane components i.e. laminin (LN) or Matrigel (MG), on the adhesion and invasion of B16-F10 melanoma cells by these TG/SPD-modified substrates. The adhesion assays showed that cell binding to the TG/SPD-modified LN was reduced by 30%, when compared to untreated LN, whereas the reduction obtained using TG/SPD modified MG was 35%. Similarly, tumor cell invasion by the Boyden chamber system through TG/SPD modified LN or MG was respectively reduced by 45%, and by 69%. Evaluation of matrix metalloproteinase (gelatinases MMP-2 and MMP-9) activities by gel-zymography showed that MMP-2 activity was unaffected, while MMP-9 activity was reduced by about 32% using TG/SPD-modified substrate. These results strongly suggest that the observed antiinvasive effect of TG activation in the host may be ascribed to the covalent incorporation of polyamines, which led to the post translational modification of some components of the cell basement membrane. This modification may interfere with the metastatic property of melanoma cells, affecting the proteolytic activity necessary for their migration and invasion activities. PMID- 17356805 TI - Polyamines and abiotic stress: recent advances. AB - In this review we will concentrate in the results published the last years regarding the involvement of polyamines in the plant responses to abiotic stresses, most remarkably on salt and drought stress. We will also turn to other types of abiotic stresses, less studied in relation to polyamine metabolism, such as mineral deficiencies, chilling, wounding, heavy metals, UV, ozone and paraquat, where polyamine metabolism is also modified. There is a great amount of data demonstrating that under many types of abiotic stresses, an accumulation of the three main polyamines putrescine, spermidine and spermine does occur. However, there are still many doubts concerning the role that polyamines play in stress tolerance. Several environmental challenges (osmotic stress, salinity, ozone, UV) are shown to induce ADC activity more than ODC. The rise in Put is mainly attributed to the increase in ADC activity as a consequence of the activation of ADC genes and their mRNA levels. On the other hand, free radicals are now accepted as important mediators of tissue injury and cell death. The polycationic nature of polyamines, positively charged at physiological pH, has attracted the attention of researchers and has led to the hypothesis that polyamines could affect physiological systems by binding to anionic sites, such as those associated with nucleic acids and membrane phospholipids. These amines, involved with the control of numerous cellular functions, including free radical scavenger and antioxidant activity, have been found to confer protection from abiotic stresses but their mode of action is not fully understood yet. In this review, we will also summarize information about the involvement of polyamines as antioxidants against the potential abiotic stress-derived oxidative damage. PMID- 17356806 TI - Oxidatively-modified and glycated proteins as candidate pro-inflammatory toxins in uremia and dialysis patients. AB - End stage renal disease (ESRD) patients accumulate blood hallmarks of protein glycation and oxidation. It is now well established that these protein damage products may represent a heterogeneous class of uremic toxins with pro inflammatory and pro-oxidant properties. These toxins could be directly involved in the pathogenesis of the inflammatory syndrome and vascular complications, which are mainly sustained by the uremic state and bioincompatibility of dialysis therapy. A key underlying event in the toxicity of these proteinaceous solutes has been identified in scavenger receptor-dependent recognition and elimination by inflammatory and endothelial cells, which once activated generate further and even more pronounced protein injuries by a self-feeding mechanism based on inflammation and oxidative stress-derived events. This review examines the literature and provides original information on the techniques for investigating proteinaceous pro-inflammatory toxins. We have also evaluated therapeutic - either pharmacological or dialytic - strategies proposed to alleviate the accumulation of these toxins and to constrain the inflammatory and oxidative burden of ESRD. PMID- 17356807 TI - Transcutaneous arterial embolization to control massive tumor bleeding in head and neck cancer: 63 patients' experiences from a single medical center. AB - BACKGROUND: Massive tumor bleeding is a life-threatening complication in patients with head and neck cancer (HNC). Tumor hemorrhage is usually hard to localize, and medical management is often ineffective. Arterial angiography is used to visualize the source of bleeding, and concurrent transcutaneous arterial embolization (TAE) can be done to stop bleeding in some patients. We analyzed the outcome of TAE in HNC patients with massive bleeding at our institution. METHOD: We retrospectively reviewed 93 angiographic procedures in 63 HNC patients. Factors potentially related to post-hemorrhagic survival were evaluated, including tumor stage (T, N, M), tumor type, previous curative-intent surgery, previous chemotherapy, previous radiotherapy, angiographic findings, the presence of embolization, and the embolization methods. RESULT: A total 56 TAEs were done in 93 angiographic procedures in 63 HNC patients. The overall median post hemorrhagic survival after angiography was 16 days (range 0-644 days). Median post-hemorrhagic survival for patients receiving TAE was 26 days (range 0-644 days), while patients who received angiography alone survived 8 days (range 0-144 days; p = 0.008). No factors other than TAE predicted post-hemorrhagic survival, and there were no major adverse events after TAE. CONCLUSION: In our hands, TAE was associated with a low incidence of toxicities commonly attributable to the procedure such as stroke. Patients who were able to undergo TAE lived longer than those who were not candidates for the procedure. PMID- 17356808 TI - The effects of tree establishment on water and salt dynamics in naturally salt affected grasslands. AB - Plants, by influencing water fluxes across the ecosystem-vadose zone-aquifer continuum, can leave an imprint on salt accumulation and distribution patterns. We explored how the conversion of native grasslands to oak plantations affected the abundance and distribution of salts on soils and groundwater through changes in the water balance in naturally salt-affected landscapes of Hortobagy (Hungary), a region where artificial drainage performed approximately 150 years ago lowered the water table (from -2 to -5 m) decoupling it from the surface ecosystem. Paired soil sampling and detailed soil conductivity transects revealed consistently different salt distribution patterns between grasslands and plantations, with shallow salinity losses and deep salinity gains accompanying tree establishment. Salts accumulated in the upper soil layers during pre drainage times have remained in drained grasslands but have been flushed away under tree plantations (65 and 83% loss of chloride and sodium, respectively, in the 0 to -0.5 m depth range) as a result of a five- to 25-fold increase in infiltration rates detected under plantations. At greater depth, closer to the current water table level, the salt balance was reversed, with tree plantations gaining 2.5 kg sodium chloride m(-2) down to 6 m depth, resulting from groundwater uptake and salt exclusion by tree roots in the capillary fringe. Diurnal water table fluctuations, detected in a plantation stand but not in the neighbouring grasslands, together with salt mass balances suggest that trees consumed approximately 380 mm groundwater per year, re-establishing the discharge regime and leading to higher salt accumulation rates than those interrupted by regional drainage practices more than a century ago. The strong influences of vegetation changes on water dynamics can have cascading consequences on salt accumulation and distribution, and a broad ecohydrological perspective that explicitly considers vegetation-groundwater links is needed to anticipate and manage them. PMID- 17356809 TI - Using delta13C stable isotopes to quantify individual-level diet variation. AB - Individual-level diet variation can be easily quantified by gut-content analysis. However, because gut contents are a 'snapshot' of individuals' feeding habits, such cross-sectional data can be subject to sampling error and lead one to overestimate levels of diet variation. In contrast, stable isotopes reflect an individual's long-term diet, so isotope variation among individuals can be interpreted as diet variation. Nevertheless, population isotope variances alone cannot be directly compared among populations, because they depend on both the level of diet variation and the variance of prey isotope ratios. We developed a method to convert population isotope variances into a standardized index of individual specialization (WIC/TNW) that can be compared among populations, or to gut-content variation. We applied this method to diet and carbon isotope data of four species of frogs of the Brazilian savannah. Isotopes showed that gut contents provided a reliable measure of diet variation in three populations, but greatly overestimated diet variation in another population. Our method is sensitive to incomplete sampling of the prey and to among-individual variance in fractionation. Therefore, thorough sampling of prey and estimates of fractionation variance are desirable. Otherwise, the method is straightforward and provides a new tool for quantifying individual-level diet variation in natural populations that combines both gut-content and isotope data. PMID- 17356810 TI - Long-term demographic analysis in goshawk Accipiter gentilis: the role of density dependence and stochasticity. AB - Density dependence and environmental stochasticity are both potentially important processes influencing population demography and long-term population growth. Quantifying the importance of these two processes for population growth requires both long-term population as well as individual-based data. I use a 30-year data set on a goshawk Accipiter gentilis population from Eastern Westphalia, Germany, to describe the key vital rate elements to which the growth rate is most sensitive and test how environmental stochasticity and density dependence affect long-term population growth. The asymptotic growth rate of the fully age structured mean matrix model was very similar to the observed one (0.7% vs. 0.3% per annum), and population growth was most elastic to changes in survival rate at age classes 1-3. Environmental stochasticity led only to a small change in the projected population growth rate (between -0.16% and 0.67%) and did not change the elasticities qualitatively, suggesting that the goshawk life history of early reproduction coupled with high annual fertility buffers against a variable environment. Age classes most crucial to population growth were those in which density dependence seemed to act most strongly. This emphasises the importance of density dependence as a regulatory mechanism in this goshawk population. It also provides a mechanism that might enable the population to recover from population lows, because a mean matrix model incorporating observed functional responses of both vital rates to population density coupled with environmental stochasticity reduced long-term extinction risk of 30% under density-independent environmental stochasticity and 60% under demographic stochasticity to zero. PMID- 17356811 TI - Arbuscular mycorrhizal fungi reduce the construction of extrafloral nectaries in Vicia faba. AB - Arbuscular mycorrhizal fungi (AMF) can alter the physiology and morphology of their host plant, and therefore may have indirect effects on insect herbivores and pollinators. We conducted this study to test the hypothesis that AMF can also affect insects involved in protection-for-food mutualisms. We examined the constitutive and inducible production of food rewards [extrafloral (EF) nectaries] in Vicia faba plants by manipulating the presence/absence of AMF and by simulating various levels of herbivory. Plants inoculated with AMF produced significantly fewer EF nectaries than uninoculated plants, even after accounting for differences in plant growth. In contrast to earlier studies, EF nectaries were not inducible: damaged plants produced significantly fewer EF nectaries than undamaged plants. Moreover, the effects of mycorrhizal and damage status on EF nectary production were additive. The reduction in EF nectaries in mycorrhizal plants potentially represents a mechanism for indirect effects of AMF on the protective insects that exploit EF nectaries as a food source (e.g., ants). Reduced reward size should result in reduced protection by ants, and could therefore be a previously unappreciated cost of the mycorrhizal symbiosis to host plants. However, the overall effect of AMF will depend upon the extent to which the reduction of EF nectaries affects the number and activity of ants and the extent to which AMF alter other aspects of host plant physiology. Our results emphasize the complexity of multitrophic interactions, particularly those that span belowground and aboveground ecology. PMID- 17356812 TI - Getting out alive: how predators affect the decision to metamorphose. AB - Metamorphosis has intrigued biologists for a long time as an extreme form of complex life cycles that are ubiquitous in animals. While investigated from a variety of perspectives, the ecological focus has been on identifying and understanding the ecological factors that affect an individual's decision on when, and at what size, to metamorphose. Predation is a major factor that affects metamorphic decisions and a recent review by Benard (Annu Rev Ecol Evol Syst 35:651-673, 2004)) documented how predator cues induce metamorphic changes relative to model predictions. Importantly, however, real predators affect larval prey via several mechanisms beyond simple induction. In this paper, I contrast the leading models of metamorphosis, provide an overview of the multiple ways that predators can directly and indirectly affect larval growth and development (via induction, thinning, and selection), and identify how each process should affect the time to and size at metamorphosis. With this mechanistic foundation established, I then turn to the well-studied model system of larval amphibians to synthesize studies on: (1) caged predators (which cause only induction), and (2) lethal predators (which cause induction, thinning, and selection). Among the caged-predator studies, the chemical cues emitted by predators rarely induce a smaller size at metamorphosis or a shorter time to metamorphosis, which is in direct contrast to theoretical predictions but in agreement with Benard's (Annu Rev Ecol Evol Syst 35:651-673, 2004) review based on a considerably smaller dataset. Among the lethal-predator studies, there is a diversity of outcomes depending upon the relative importance of induction versus thinning with the relative importance of the two processes appearing to change with larval density. Finally, I review the persistent effects of larval predators after metamorphosis including both phenotypic and fitness effects. At the end, I outline a number of future directions to allow researchers to continue gaining insight into how predators affect the metamorphic decisions of their prey. PMID- 17356813 TI - Tree species diversity influences herbivore abundance and damage: meta-analysis of long-term forest experiments. AB - Plant monocultures are commonly believed to be more susceptible to herbivore attacks than stands composed of several plant species. However, few studies have experimentally tested the effects of tree species diversity on herbivory. In this paper, we present a meta-analysis of uniformly collected data on insect herbivore abundance and damage on three tree species (silver birch, black alder and sessile oak) from seven long-term forest diversity experiments in boreal and temperate forest zones. Our aim was to compare the effects of forest diversity on herbivores belonging to different feeding guilds and inhabiting different tree species. At the same time we also examined the variation in herbivore responses due to tree age and sampling period within the season, the effects of experimental design (plot size and planting density) and the stability of herbivore responses over time. Herbivore responses varied significantly both among insect feeding guilds and among host tree species. Among insect feeding guilds, only leaf miner densities were consistently lower and less variable in mixed stands as compared to tree monocultures regardless of the host tree species. The responses of other herbivores to forest diversity depended largely on host tree species. Insect herbivory on birch was significantly lower in mixtures than in birch monocultures, whereas insect herbivory on oak and alder was higher in mixtures than in oak and alder monocultures. The effects of tree species diversity were also more pronounced in older trees, in the earlier part of the season, at larger plots and at lower planting density. Overall our results demonstrate that forest diversity does not generally and uniformly reduce insect herbivory and suggest instead that insect herbivore responses to forest diversity are highly variable and strongly dependent on the host tree species and other stand characteristics as well as on the type of the herbivore. PMID- 17356814 TI - Establishment of grassland species in monocultures: different strategies lead to success. AB - The establishment pattern of monocultures of 61 species common to Central European semi-natural grasslands was analysed in a field experiment. The objectives were to identify key traits for successful establishment, defined in terms of above-ground biomass production, and to characterize the degree of niche overlap with respect to the use of above-ground resources, such as light and space. Four months after sowing, 15 species reached an above-ground biomass of more than 400 g m(-2). Highly productive monocultures adopted extremely different strategies of space filling in terms of canopy height, biomass density and centre of gravity of vertical biomass distribution. Regression tree analysis identified (1) the number of seedlings and (2) a trade-off between the development of a large number of small-sized shoots of species with intensive clonal growth in contrast to the establishment of fewer large-sized shoots as the two most important traits for successful establishment. Further variables associated with high above-ground biomass production by individual species were traits known to be relevant to the relative growth rate of herbaceous species, such as specific leaf area, leaf nitrogen or allocation between shoots and roots. The principle finding of this study is that the success of the 15 most productive species was not based on a single pathway but on a variable combination of traits. There are clearly many possible combinations of morphological and physiological features that will result in a species becoming productive, and these combinations differ among species in a local species pool. PMID- 17356815 TI - Stir-bar-sorptive extraction, with in-situ deconjugation, and thermal desorption with in-tube silylation, followed by gas chromatography-mass spectrometry for measurement of urinary 4-nonylphenol and 4-tert-octylphenol glucuronides. AB - A novel method, stir-bar-sorptive extraction (SBSE), with in-situ deconjugation and thermal desorption (TD) with in-tube silylation, followed by gas chromatography-mass spectrometry (GC-MS), for determination of trace amounts of 4 nonylphenol glucuronide (NP-G) and 4-tert-octylphenol glucuronide (OP-G) in human urine, is described. The method involved correction by use of stable isotopically labeled internal standards 4-(1-methyl)octylphenol-d5 (NP-d) and deuterium 4-tert octylphenol (OP-d). A human urine sample to which beta-glucuronidase had been added was extracted for 90 min at 37 degrees C using a stir bar coated with a 500 microm-thick layer of polydimethylsiloxane (PDMS). NP-G and OP-G were deconjugated, becoming free 4-nonylphenol (NP) and 4-tert-octylphenol (OP). The analytes were then extracted with the PDMS stir bar and the stir bar was subjected to TD with in-tube silylation; this was followed by GC-MS in selected ion-monitoring (SIM) mode. To optimize the conditions for SBSE with in-situ deconjugation and to test recovery, NP-G and OP-G were synthesized by a biochemical technique in our laboratory. Average recoveries from human urine samples spiked with NP-G and OP-G were between 91.9 and 95.6% with correction using the added surrogate standards. Limits of detection were 0.11 ng mL-1 for NP and 0.01 ng mL-1 for OP. We also measured background levels of NP-G and OP-G in six urine samples from healthy volunteers. NP and OP were detected in the samples at concentrations of 0.62-1.95 ng mL-1 and <0.04-0.18 ng mL-1, respectively. PMID- 17356816 TI - Practical evaluation of universal conditions for four-plex quantitative PCR. AB - Multiplexing quantitative polymerase chain reaction (qPCR) is a powerful way to substantially increase the number of genes that can be analyzed, while also reducing sample requirements, time, and cost. However, little previous work has been done to show its feasibility for multiple gene targets. Here, we determined optimal conditions for four-color multiplex qPCR. On the basis of amplification curves, we first established that the concentration of probe-primers should be about tenfold lower than that for conventional qPCR. This condition was evaluated using four sets of probe-primers labeled with FAM, CAL Fluor Orange, TAMRA, and Quasar670, respectively. To simulate the condition that different genes have different levels of transcript abundance, a series of test samples was prepared by mixing a constant amount of two kinds of vector together with different amounts of two other vectors in a four-plex qPCR format. The PCR efficiency of the constant genes was minimally affected by the presence of the spiked vectors, and the slope factors of standard curves for the two spiked genes were sufficient for the accurate quantification. We demonstrated here that qPCR in a four-plexed format is feasible for cost-effective practical use through a combination of lower concentrations of probe-primers, an appropriate reagent, and a detection instrument. PMID- 17356817 TI - New cloud vapor zone (CVZ) coupled headspace solid-phase microextraction technique. AB - A new cloud vapor zone (CVZ)-based headspace solid-phase microextraction (HS SPME) technique has been demonstrated with the capability of heating the sample matrix and simultaneously cooling the sampling zone. A bi-temperature-controlled (BTC) system, allowing 10 mL of test sample heating and headspace external cooling, was employed for the CVZ formation around the SPME-fiber sampling area. In the CVZ procedure, the heated headspace vapor undergoes a sudden cooling near the SPME to form a dense cloud of analyte-water vapor, which is helpful for adsorption or absorption of the analyte. The device was evaluated for the quantitative analysis of aqueous chlorothalonil. Parameters influencing sampling efficiency, e.g., SPME fiber coating, SPME sampling temperature and time, solution modifier, addition of salt, sample pH, and temperature, were investigated and optimized thoroughly. The proposed BTC-HS-SPME method afforded a best extraction efficiency of above 94% accuracy (less than 4.1% RSD, n=7) by using the PDMS fiber to collect chlorothalonil in the headspace at 5 degrees C under the optimized condition, i.e., heating sample solution (added as 10% ethylene glycol and 30% NaCl, at pH 7.0) at 130 degrees C for 15 min. The detection was linear from 0.01 to 80 microg L-1 with a regression coefficient of 0.9998 and had a detection limit of 3.0 ng L-1 based on S/N=3. Practical application was demonstrated by analyzing chlorothalonil in farm water samples with promising results and recoveries. The approach provided a very simple, fast, sensitive, and solvent-free procedure to collect analytes from aqueous solution. The approach can provide a new platform for other sensitive HS-SPME assays. PMID- 17356818 TI - DNA purification on a lab-on-valve system incorporating a renewable microcolumn with in situ monitoring by laser-induced fluorescence. AB - Bead injection in a lab-on-valve (LOV) system was adopted for DNA purification via micro solid-phase extraction (SPE) with a renewable silica microcolumn packed in a channel of the LOV unit. The complex matrix components in human whole blood, including proteins, were well eliminated by choosing properly the sample loading and elution media. The DNA purification process was monitored on-line by using laser-induced fluorescence in a demountable side part of the LOV unit incorporating optical fibers. The practical applicability of the entire system was demonstrated by separation/purification of lambda-DNA in a simulated matrix and human blood genetic DNA by performing SPE, in situ monitoring of the purified products, and postcolumn PCR amplification. When DNAs in a simulated matrix (10.0 ng microl-1 lambda-DNA, 50 ng microl-1 bovine serum albumin, 1.0% Triton X-100) were processed in the present system and laser-induced fluorescence was monitored at 610 nm, an overall extraction/collection efficiency of 70% was achieved by employing identical sample loading and an elution flow rate of 0.5 microl s-1, along with a precision of 3.8% relative standard deviation. DNA separation and purification from human whole-blood samples were performed under similar conditions. PMID- 17356819 TI - Derivatization of organophosphorus nerve agent degradation products for gas chromatography with ICPMS and TOF-MS detection. AB - Separation and detection of seven V-type (venomous) and G-type (German) organophosphorus nerve agent degradation products by gas chromatography with inductively coupled plasma mass spectrometry (GC-ICPMS) is described. The nonvolatile alkyl phosphonic acid degradation products of interest included ethyl methylphosphonic acid (EMPA, VX acid), isopropyl methylphosphonic acid (IMPA, GB acid), ethyl hydrogen dimethylamidophosphate sodium salt (EDPA, GA acid), isobutyl hydrogen methylphosphonate (IBMPA, RVX acid), as well as pinacolyl methylphosphonic acid (PMPA), methylphosphonic acid (MPA), and cyclohexyl methylphosphonic acid (CMPA, GF acid). N-(tert-Butyldimethylsilyl)-N methyltrifluroacetamide with 1% TBDMSCl was utilized to form the volatile TBDMS derivatives of the nerve agent degradation products for separation by GC. Exact mass confirmation of the formation of six of the TBDMS derivatives was obtained by GC-time of flight mass spectrometry (TOF-MS). The method developed here allowed for the separation and detection of all seven TBDMS derivatives as well as phosphate in less than ten minutes. Detection limits for the developed method were less than 5 pg with retention times and peak area precisions of less than 0.01 and 6%, respectively. This method was successfully applied to river water and soil matrices. To date this is the first work describing the analysis of chemical warfare agent (CWA) degradation products by GC-ICPMS. PMID- 17356820 TI - Transtibial double bundle posterior cruciate ligament reconstruction using TransFix tibial fixation. AB - Previous transtibial double bundle posterior cruciate ligament (PCL) reconstruction methods have several problems in graft length and tibial fixation. We introduce new surgical method that is less restrictive by graft length and is more stable with single tibial fixation. After diagnostic arthroscopy, we prepare the graft, ream the tibial tunnel, and perform the procedure for TransFix tibial fixation. Femoral 2 tunnel is made and graft is passed via anteromedial (AM) portal. Tibial fixation is done and femoral 2 graft is fixed sequentially at each knee position. TransFix tibial single fixation method in double bundle PCL reconstruction provides more stable fixation, more free graft selection, and prevents graft damage by passing the graft via AM portal. PMID- 17356821 TI - Video-assisted thoracoscopic surgery (VATS) for the treatment of scolioticrib hump deformity. AB - A retrospective study of 21 patients with idiopathic scoliosis who underwent endoscopic thoracoplasty was done. The objective of the study was to report and assess the morbidity and mid term outcomes of video-assisted thoracoplasty in idiopathic scoliosis. Patients with idiopathic scoliosis often present cosmetic complaints due to their rib deformity. This deformity may still exist after surgical correction of the main scoliotic curve. Endoscopic thoracoplasty has been reported as a safe method in limited cases of idiopathic scoliosis. Between 2002 and 2004, 21 patients underwent endoscopic anterior release and thoracoplasty for significant rib hump deformity associated with idiopathic scoliosis. Patients were operated on lateral position, with two endoscopic ports. Anterior release and rib resection were performed during the first stage, and instrumented posterior fusion was performed in a second stage. Patients were evaluated preoperatively, 1 week after surgery, 6 months after surgery and at their most recent follow-up with clinical and radiological measurement of the rib deformity. The mean age at surgery was 14.9 years old (range 13-17 years). The average Cobb's angle of the main scoliotic curve was 70 degrees (range 60 degrees -85 degrees). Average follow-up was 25 months (range 23-32 months). The mean number of resected ribs was five ribs (range 4-7) and the mean length of the resected rib was 4.2 cm (range 2.2-7 cm). Average operating time of endoscopic thoracoplasty (including anterior release) was 65 min (range 45-108 min). The mean preoperative height of rib hump deformity was 3.6 cm (range 2.5-5.5 cm). It was reduced to 1.5 cm at most recent follow-up. There was no significant thoracic pain necessitating medication postoperatively. No complications related to endoscopic anterior release and rib hump resection occurred in the series. Endoscopic thoracoplasty is a safe and reliable technique in idiopathic scoliosis. If indicated, the anterior release can be performed with video assistance and the thoracoplasty can be performed on the same stage. PMID- 17356822 TI - Comparison of pharmacokinetic and metabolic profiling among gossypol, apogossypol and apogossypol hexaacetate. AB - PURPOSE: To characterize the stability, pharmacokinetics and metabolism of analogs of gossypol, apogossypol and apogossypol hexaacetate to provide a basis for comparison. METHODS: Gossypol, apogossypol and apogossypol hexaacetate were incubated in plasma or liver microsomes from various species, or administered to mice, respectively, from which the stability, metabolism and pharmacokinetic profiles of these analogs were quantitatively determined using a liquid chromatography-mass spectrometry (LC/MS/MS) method. RESULTS: In various species of plasma, apogossypol and gossypol exhibited similar stability, while 20-40% of apogossypol hexaacetate was converted into apogossypol with concurrent formation of the corresponding di-, tri-, tetra-, and penta-acetates of apogossypol. (+/-) Gossypol and (-)-gossypol showed comparable pharmacokinetic profile and oral bioavailability (12.2-17.6%) with some variations of clearance and V (ss) following oral and intravenous administration to mice. At the same molar dose, apogossypol showed delayed T (max)(1 h), a slower clearance rate and less distribution after administration to mice. Mono- and di-glucuronide conjugates of apogossypol were readily observed in mouse plasma following administration. Apogossypol formulated in sesame oil appeared to possess larger AUC and thus higher oral bioavailability than that formulated in cremophor EL:ethanol:saline. In contrast, intravenous apogossypol hexaacetate exhibited highest clearance rate partially due to its conversion into apogossypol. Concomitant with disappearance of apogossypol hexaacetate (iv), apogossypol converted from apogossypol hexaacetate was quantitatively detected, and accounted for approximately 30% of total plasma apogossypol hexaacetate. Oral apogossypol hexaacetate showed no bioavailability with little apogossypol occurring in the plasma. In human and mouse liver microsomes, glucuronide conjugates of apogossypol and its acetates were readily identified with the exception of gossypol glucuronidation. Apogossypol appeared more stable in human and mouse liver microsomal preparations than gossypol and apogossypol hexaacetate. CONCLUSIONS: Apogossypol and gossypol show similar oral and intravenous pharmacokinetic profiles and in vitro stability although apogossypol appears to have a slower clearance rate, larger AUC, and better microsomal stability. Apogossypol hexaacetate converts to apogossypol in both in vitro and in vivo settings and lacks any quantifiable oral bioavailability. PMID- 17356823 TI - Modification of multidrug resistance of tumor cells by ionizing radiation. AB - PURPOSE: The effect of ionizing radiation on multidrug resistance (MDR) of human larynx cancer HEp-2 cells has been investigated. We studied the dependence of the radiation effect on radiation dose, time after irradiation and cell density. METHODS: MDR was determined from an increase in cell sensitivity to daunorubicin, taxol and vincristine by the inhibitors of multidrug resistance cyclosporin A and avermectin B(1), and from the suppression by cyclosporin A of the transport of rhodamine 123 out of the cells. The cells were irradiated with X-ray beams (dose rate 1.12 Gy min(-1)) at room temperature. RESULTS: It was shown that, at 8 and 16 h after irradiation with doses up to 4 Gy, the multidrug resistance of cells increases, and at 24 h it decreases to the control level. The effect was maximal by 16 h after irradiation with a dose of 1 Gy. Both, the contribution of active transport to the rate of rhodamine 123 efflux from cells and their resistance to vincristine, increased. The effect of irradiation on multidrug resistance of HEp 2 cells depended on the density of cells on the substrate, being maximal at a density of 80,000-100,000 cm(-2). CONCLUSION: The irradiation-induced changes in the MDR of tumor cells should be taken into account when combining radiotherapy with chemotherapy. It was assumed that the dependence of multidrug resistance of HEp-2 cells on radiation dose and cell density is determined by changes in the amount of reactive oxygen species in the cells. PMID- 17356825 TI - Magnetic resonance imagining (MRI) and serial beta-human chorionic gonadotrophin (beta-hCG) follow up for placenta percreta. AB - BACKGROUND: Placenta percreta is a rare obstetric condition associated with life threatening hemorrhage. MR imaging has a role in prenatal diagnosis of these cases. However, its role in the postnatal diagnosis and in the follow up yet to be established. CASE: A 33-year-old patient has adherent placenta following spontaneous delivery at 37 weeks gestation. MR imaging diagnosed placenta percreta. Intramuscular methotrexate treatment was initiated with follow up with serial beta-human chorionic gonadotrophin (beta-hCG). In spite of dropping of the level of beta-hCG, the trophoblastic tissue was still present 6 weeks postnatally where the patient complained of vaginal bleeding where she opted to abdominal hysterectomy. CONCLUSION: Patients who are suitable for non-surgical therapy, T2 weighted MR imaging may, in conjunction with serial beta-hCG assays, provide an alternative treatment modality for cases of placenta percreta. PMID- 17356824 TI - Bevacizumab in retinal vein occlusion-results of a prospective case series. AB - BACKGROUND: Macular edema is the main reason for decreased visual acuity (VA) in early retinal vein occlusion (RVO). Bevacizumab (Avastin, Genentech) is an anti VEGF substance to treat macular edema triggered by hypoxia-induced expression of vascular endothelial growth factor (VEGF). Initial reports showed a significant reduction of central retinal thickness and improved visual acuity (VA) after bevacizumab injection. To date, only retrospective studies and case reports have been published on bevacizumab treatment of RVO. METHODS: In this prospective interventional case series, we evaluated the response to a single bevacizumab treatment in 21 RVO patients (14 CRVO, 7 BRVO). Study endpoints were visual acuity (VA) using ETDRS charts and central macular edema (CME) over 9 weeks. RESULTS: Mean VA from all 21 patients increased by more than 2 lines (2.4+/-0.4 lines; p<0.01 compared to baseline). The improvement of VA after bevacizumab injection was concordant with a decrease in central retinal thickness. Peak VA was reached between 3 and 6 weeks after injection. Between week 6 and 9 a decrease in VA was observed. This VA decrease was precipitated by an increase in CME between week 3 and 6. In subgroup analyses, patients receiving bevacizumab injection within the first 3 months after RVO showed an average VA gain of 4 lines (range 2-7 lines) compared to an average gain of 1.8 (range 1-3) and 2.5 (range 1-7) in patients receiving bevacizumab between 4-6 months and after more than 6 months, respectively. CONCLUSIONS: Bevacizumab injection is able to improve CME and VA in RVO patients within the first 3 to 9 weeks. We did not observe any short-term adverse effects during our study. As the decrease in VA was anticipated by an increase in central retinal thickness, regular OCT examinations between week 3 and 6 may be helpful for judging the appropriate timing for re-injection in order to maintain patients within the initially reached range of VA until a new balance between inflow and outflow in the retinal circulation is reached. PMID- 17356826 TI - Comparison of two- and three-dimensional ultrasonography in the evaluation of fetal heart: image quality and time spent in the exam. AB - OBJECTIVES: To compare fetal heart evaluation done through two-dimensional (2DUS) and three-dimensional ultrasonography (3DUS) as to optimal plane imaging, image quality, and time needed to perform the examination. METHODS: Prospective study involving 12 normal pregnant women, with gestational ages ranging from 22 to 26 weeks, scanned with a VOLUSON 730 with a convex 4.0-7.0 MHz transducer, in both two- and three-dimensional modes. In each case, three basic view planes were obtained: four-chambers view, right, and left ventricular outflow tracts. Each view was subjectively evaluated by three different examiners as to image quality, and graded from 0 (minimum) to 4 (maximum) cross-marks (+). The sum of all grades obtained for each case was used to classify the quality of the exam as unsatisfactory (0 to 1+), poor (2 to 4+), regular (5 to 7+), and good (8 to 12+). The time taken to obtain the views was recorded for each case, starting with the acquisition of the first view on the 2D exam and with the identification and opening of the volume blocks on the three-dimensional software. RESULTS: The number of three-dimensional blocks with good, regular, poor, and unsatisfactory grades were, respectively, 6, 15, 9, and 10. The average in cross-marks of the cases graded good in each group without the worst result for each plane was 8. 2DUS was superior to 3DUS regarding the quality of the images obtained by the three pattern view planes and the average time to obtain high quality view planes was longer for 3DUS when compared to 2DUS. 2DUS offered better quality images and in less time than 3DUS. CONCLUSIONS: Three-dimensional ultrasound is an advancement in fetal heart evaluation; however two-dimensional ultrasound remains the best screening method in diagnosing cardiac malformations, due to the good quality of its images and the lesser time needed to perform the exam. PMID- 17356827 TI - Pregnancy in a patient with a displaced levonorgestrel-releasing intrauterine system: a case report. AB - We report the case of a 39-year-old woman who became pregnant despite a levonorgestrel-releasing intrauterine system (LNG-IUS), which was inserted 40 months before the pregnancy was detected. When a Caesarean section was performed, the LNG-IUS was found within the omentum majus. It has been reported, that displaced LNG-IUS can cause amenorrhea and high plasma levels of LNG in affected women, probably due to the higher resorptive capacity of the peritoneum, recommending a removal of the displaced LNG-IUS. Our case report demonstrates that a dislocated LNG-IUS does not necessary has the ability to suppress ovulation and therefore pregnancy. Therefore, every gynaecologist should be aware of a pregnancy despite a dislocated LNG-IUS. PMID- 17356829 TI - [Stump retention and extension on the lower extremity]. AB - Despite new techniques and better health programs in western industrialized nations, the numbers of amputations on the lower extremity remain constant. Approximately 100,000 amputations are performed annually in the U.S. and about 10,000 in Germany, more than 90% for gangrene resulting from ischemia and/or infection. Micro- and macroangiopathic changes in diabetes are the major cause of ischemia in the leg. The preservation of limb length and construction of an end bearing stump are important criteria for the functional outcome after amputation. Especially in trauma and tumor patients with "planned" amputations, all effort should be made to achieve an end bearing stump with sufficient length respectively an amputation level that is suitable for orthosis instead of prosthetic supplementation. After amputation, an interdisciplinary approach is mandatory to achieve sufficient soft tissue coverage or stump distalization. In case of insufficient bearing ability of the stump, various reconstructive possibilities must be considered to assure optimal outcome. PMID- 17356830 TI - [Quality assurance and infection control in outpatient surgery]. AB - BACKGROUND: According to the German Law on Infectious Diseases (Infektionsschutzgesetz or IfSG) German outpatient centres must provide evidence of maintaining certain standards of hygiene and record their nosocomial infection rates. To fulfill their legal obligations, the Commission for Hospital Hygiene and the Prevention of Infection recommends surveillance modules such as that known as AMBU-KISS. MATERIALS AND METHODS: The AMBU-KISS project centre implemented a survey to evaluate all procedures relevant to hygiene, surveillance of surgical site infections, and facilities available at centres participating in the AMBU-KISS surveillance programme. The questionnaire was returned by 99 of 110 participants. RESULTS AND DISCUSSION: All the centres possess cleaning and disinfection schemes, and practically all of them use written instructions on the processing of instruments and surgical hand disinfection procedure. Many of the participants spend too much time on surgical hand disinfection and presurgical skin disinfection. CONCLUSION: The survey demonstrates that hygienic conditions at centres participating in AMBU-KISS are largely satisfactory. However, there is nevertheless a need to optimise infection control measures. PMID- 17356831 TI - [Therapy options in relapsing prostate cancer after external radiation therapy]. AB - In the near future, the number of young patients suffering from locoregional recurrence of their prostate cancer after external beam radiation will increase. For these patients, androgen deprivation is the most widely used therapy, but it is only palliative. Salvage radical prostatectomy, cryoablation, interstitial brachytherapy, and high-intensity focused ultrasound (HIFU) are treatment options with the potential of curing the patient. Currently, salvage radical prostatectomy offers the best chance for cure. Although a significant reduction in peri- and postoperative complication rates has been reported, surgery remains technically challenging, with a high rate of urinary incontinence. We believe that salvage prostatectomy should be considered only for patients in good general health whose life expectancy is more than 10 years and whose cancer was initially organ-confined before radiation therapy. Salvage cryotherapy might be an alternative to surgery. Complication rates have decreased as technical application has improved considerably within the last years. A major drawback of cryoablation is its lack of reliable and complete ablation of all prostate cells. HIFU and interstitial brachytherapy are minimally invasive salvage options that have been investigated in small clinical studies. PMID- 17356832 TI - [Introduction to the topic: incontinence in the aged--(un)avoidable?]. PMID- 17356833 TI - [Treatment of overactive bladder in elderly and old people]. AB - Overactive bladder syndrome is a widespread disorder that leads to considerable impairment of quality of life. Besides behavioural therapy (bladder training), methods used in physiotherapy, electrotherapy and instrumental biofeedback have also proved to be successful approaches to treatment. With their good clinical and urodynamic efficacy, substances with antimuscarinic action at M3 receptors in particular and possibly also at M2 receptors have proved successful as first-line agents for the treatment of overactive bladder (OAB). Despite the frequently high level of suffering and severe impairment of quality of life, however, compliance is poor. Muscarine receptors do have a significant effect on detrusor function, but numerous other mechanisms and receptor entities also play a role. Whether patient acceptance can be significantly increased by the development of selective M-receptor antagonists, improved bladder selectivity or formulating innovations remains to be proven by broad-based clinical testing and independent, comparative, scientific studies. At present, it is not possible to estimate with absolute certainty the risk of an anticholinergic-induced deterioration in cognitive abilities, in particular in elderly individuals. Initial data suggest that primarily M3-selective receptor blockage with darifenacin could be beneficial. PMID- 17356834 TI - [Magnetic stimulation of the pelvic floor in older patients. Results of a prospective analysis]. AB - Since 2001 magnetic stimulation therapy has been available in Germany for treating urinary incontinence as an alternative to traditional electrical stimulation therapy. The results of 83 patients who underwent magnetic stimulation therapy for stress incontinence, OAB, and pelvic pain syndrome were evaluated. The results differed depending on the underlying disease. Patients with stress incontinence who could not properly contract pelvic floor muscles before could do so in 74% when clinically evaluated and patients with OAB symptoms improved in 54% as assessed by objective and subjective criteria, whereas patients with pelvic pain syndrome only benefited in 23%. Comparison of the results according to age revealed no significant difference between patients >65 years and younger patients. PMID- 17356835 TI - [Epidemiology and etiology of urinary incontinence in the elderly]. AB - Urinary incontinence is an important and common health problem, whose prevalence increases with age. Often quality of life is clearly affected for persons concerned. In the group of elderly individuals (> or =60 years of age) 19.3% of women and 10.4% of men report urinary incontinence. Women most frequently describe urinary stress incontinence followed by incontinence with urge symptoms (urge incontinence, mixed incontinence). In men urinary incontinence without any symptoms of stress or urge incontinence is most common followed by incontinence with urge symptoms and stress incontinence. Urinary incontinence in the elderly is rarely due to a single reason but rather due to multiple factors. In urinary stress incontinence, a differentiation can be made between mechanical and functional problems of the sphincter mechanism caused by myogenic, neurogenic, hormonal, or iatrogenic factors as well as changes in connective tissue. In urinary incontinence with urge symptoms, geriatric detrusor function is mostly affected by neurogenic, myogenic, or urothelial factors whereas the detrusor muscle shows characteristic ultrastructural changes. In chronic urinary retention with consecutive urinary incontinence, especially in men infravesical obstruction is more often the reason than a geriatric bladder dysfunction. PMID- 17356836 TI - [Immunotherapy of metastatic renal cell carcinoma with interleukin-2, interferon alpha2a and erythropoietin-beta]. AB - BACKGROUND: The combination of interferon-alpha2a (IFN-alpha2a) and interleukin-2 (IL-2) induces objective responses in patients with metastatic renal cell carcinoma (MRCC). Anaemia is associated with poor cancer control and reduced quality of life. The aim of the study was to investigate response rate and quality of life in patients with MRCC receiving the combination of Erythropoetin, IFN-alpha2a and IL-2. MATERIAL AND METHOD: Patients with MRCC received epoetin beta (150 IU/kg and haemoglobin <130 g/l or 75 IU/kg and haemoglobin >or=130 g/l) three times weekly, from 14 days before and continuing throughout immunotherapy. In weeks 3-6 the patients received IFN-alpha2a 6 x 10(6) IU/m2 and IL-2 4.5 x 10(6) IU/m2 three times weekly on days 1, 3 and 5. The treatment was repeated two times and in the case of success a third cycle was added. The quality of life was assessed with the FACT questionnaire for fatigue, before, during and after therapy. RESULTS: A total of 21 patients were treated, 19 of whom could be evaluated concerning response, toxicity and quality of life. We observed 1 complete remission, 2 partial remissions, 5 cases of stable disease and 11 with progressive disease. The overall response rate was 16%. Toxicity was mild to moderate; there were no WHO grade III or IV toxicity. The quality of life increased in ten patients, nine of whom exhibited an increase in their haemoglobin during therapy. Five of the nine patients with decreased quality of life also experienced a decrease in their haemoglobin. The correlation of increased haemoglobin and quality of life was significant (p<0.05). CONCLUSION: The combination of IFN-alpha2a, IL-2 and epoetin beta resulted in objective remissions with mild to moderate toxicity. The quality of life correlates significantly with increasing haemoglobin. PMID- 17356837 TI - [The value of intravesical electrostimulation in the treatment of acute prolonged bladder overdistension]. AB - BACKGROUND: The effectiveness of intravesical electrostimulation (IVES) in the treatment of acute prolonged bladder overdistension (PBO) was investigated. METHODS: Sixteen patients (female 11, male 5, o 54 years) after PBO (bladder filling volume: 1317+/-320 ml) were evaluated: 11 after surgery and 5 after polytrauma, psychosomatic disorder or LV4 fracture. After exclusion of a neurogenic aetiology and a urodynamic examination, IVES was performed besides IC or suprapubic catheter. RESULTS: Group 1: six patients with a weak detrusor (p(detr. max.)<30 cmH(2)O); group 2: ten patients had detrusor acontractility. After 25 IVES sessions, group 1 showed a significant increase of p(detr. max.) (p=0.01) as well as a decrease in PVR (31% to 3% of bladder capacity, p=0.02). Group 2 had no significant increase of p(detr. max). CONCLUSIONS: Two-thirds of patients with a weak detrusor after PBO will regain balanced voiding after IVES due to detrusor reinforcement. With an acontractile detrusor only bladder sensation improves. PMID- 17356838 TI - Towards an understanding of the mechanics underlying aortic dissection. AB - Acute aortic dissection and associated aortic catastrophes are among the most devastating forms of cardiovascular disease, with a remarkably high morbidity and mortality despite current medical and surgical treatment. The mechanics underlying aortic dissection are incompletely understood, and a further understanding of the relevant fluid and solid mechanics may yield not only a better appreciation of its pathogenesis, but also the development of improved diagnostic and therapeutic strategies. After illustrating some of the inadequacies with respect to the extant work on the mechanics of aortic dissection, we alternatively postulate that the clinical hemodynamic disturbances that render the aorta susceptible to the initiation of dissection are principally elevated maximum systolic and mean aortic blood pressure, whereas the hemodynamic disturbances that facilitate propagation of dissection are principally elevated pulse pressure and heart rate. Furthermore, abnormal aortic mechanical properties and/or geometry are requisite for dissection to occur. Specifically, we propose that the degree of anisotropy will directly influence the probability of future aortic dissection. Imaging of the aorta may provide information regarding aortic anisotropy and geometry, and in combination with a hemodynamic risk assessment, has the potential to be able to prospectively identify patients at high risk for future aortic dissection thereby facilitating prophylactic intervention. The aim of the paper is to identify the main mechanical issues that have a bearing on aortic dissection, and to suggest an appropriate mathematical model for describing the problem. PMID- 17356839 TI - Comment on: Tchoukalova Y, Koutsari C, Jensen M (2007) Committed subcutaneous preadipocytes are reduced in human obesity. Diabetologia 50:151-157. PMID- 17356840 TI - Quantitative diffusion-weighted MR imaging in the differential diagnosis of breast lesion. AB - The role of diffusion-weighted magnetic resonance imaging (DWI) to differentiate breast lesions in vivo was evaluated. Sixty women (mean age, 53 years) with 81 breast lesions were enrolled. A coronal echo planar imaging (EPI) sequence sensitised to diffusion (b value=1,000 s/mm(2)) was added to standard MR. The mean diffusivity (MD) was calculated. Differences in MD among cysts, benign lesions and malignant lesions were evaluated, and the sensitivity and specificity of DWI to diagnose malignant and benign lesions were calculated. The diagnosis was 18 cysts, 21 benign and 42 malignant nodules. MD values (mean +/- SD x 10(-3) mm(2)/s) were (1.48 +/- 0.37) for benign lesions, (0.95 +/- 0.18) for malignant lesions and (2.25 +/- 0.26) for cysts. Different MD values characterized different malignant breast lesion types. A MD threshold value of 1.1 x 10(-3) mm(2)/s discriminated malignant breast lesions from benign lesions with a specificity of 81% and sensitivity of 80%. Choosing a cut-off of 1.31 x 10(-3) mm(2)/s (MD of malignant lesions -2 SD), the specificity would be 67% with a sensitivity of 100%. Thus, MD values, related to tumor cellularity, provide reliable information to differentiate malignant breast lesions from benign ones. Quantitative DWI is not time-consuming and can be easily inserted into standard clinical breast MR imaging protocols. PMID- 17356841 TI - Feasibility of a RARE-based sequence for quantitative diffusion-weighted MRI of the spine. AB - The feasibility of a diffusion-weighted single-shot fast-spin-echo sequence for the diagnostic work-up of bone marrow diseases was assessed. Twenty healthy controls and 16 patients with various bone marrow pathologies of the spine (bone marrow edema, tumor and inflammation) were examined with a diffusion-weighted single-shot sequence based on a modified rapid acquisition with relaxation enhancement (mRARE) technique; four diffusion weightings (b-values: 50, 250, 500 and 750 s/mm(2)) in three orthogonal orientations were applied. Apparent diffusion coefficients (ADCs) were determined in the bone marrow and in the intervertebral discs of healthy volunteers and in diseased bone marrow. Ten of the 20 volunteers were repeatedly scanned within 30 min to examine short-time reproducibility. Spatial reproducibility was assessed by measuring ADCs in two different slices including the same lesion in 12 patients. The ADCs of the lesions exhibited significantly higher values, (1.27 +/- 0.32)x10(-3) mm(2)/s, compared with healthy bone marrow, (0.21 +/- 0.10)x10(-3) mm(2)/s. Short-time and spatial reproducibility had a mean coefficient of variation of 2.1% and 6.4%, respectively. The diffusion-weighted mRARE sequence provides a reliable tool for determining quantitative ADCs in vertebral bone marrow with adequate image quality. PMID- 17356842 TI - Biliary cystadenoma of the left intrahepatic duct (2007: 2b). AB - Biliary cystadenoma is a rare epithelial cystic neoplasm representing only 5% of intrahepatic cystic lesions of biliary origin. Commonly, the lesions are solitary cystic structures with multiple thin-walled septa predominantly arising from the right hepatic duct. Although the lesions are generally intrahepatic, extrahepatic tumors have been reported. Biliary cystadenomas range in diameter from 1.5 to 35 cm. The tumor usually affects middle-aged women. Clinical symptoms are related to the mass effect and comprise episodes of jaundice due to biliary obstruction and intermittent upper abdominal pain. Laboratory parameters are nonspecific. As the tumor is considered a premalignant lesion, complete surgical resection is the treatment of choice. We report a case of typical biliary cystadenoma of the left hepatic duct. PMID- 17356843 TI - Generation of robust cytotoxic T lymphocytes against prostate specific antigen by transduction of dendritic cells using protein and recombinant adeno-associated virus. AB - Prostate cancer is the most common male cancer and there is an urgent need for adjuvant therapy such as immunotherapy. Recombinant adeno-associated virus type 2 (rAAV) vectors are useful for antigen gene-loading of human dendritic cells (DC) and for the rapid generation of cytotoxic T lymphocytes (CTL). In this study, we report a protocol for AAV-loading of DC with the AAV-loading of self-antigen prostate specific antigen (PSA) resulting in generation of CTL. PSA and cytokine expression, Cell surface marker analysis of DC and CTL cells were done using a FACScalibur flow cytometer. Chromium-51 release assay was used to analyze the killing activity of CTL. It was found that AAV-loading of DC with the PSA gene is superior to PSA protein loading of the same antigen for generating effective CTL. AAV/PSA-loading of DC was found to result in: (1) strong, rapid PSA-specific, MHC Class I-restricted CTL, (2) PSA expression in DC, (3) high CD80, CD83, and CD86 expression on DC, (4) high level of IL-12 and low level of IL-10 in DC, (5) T cell populations with significant interferon gamma (IFNgamma) expression, but low IL-4 expression, (6) high proliferation of T cell populations, (7) high CD8:CD4 and CD8:CD56 T cell ratios. The reason for generation of robust CTL is partly explained by the characteristics of DC and CTL described. This protocol may be useful for adoptive immunotherapy against self antigens such as PSA for prostate cancer. PMID- 17356844 TI - Titrating angiotensinogen in salt sensitive hypertension. PMID- 17356845 TI - 3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3. AB - Patients with glutaryl-CoA dehydrogenase (GCDH) deficiency accumulate glutaric acid (GA) and 3-hydroxyglutaric acid (3OH-GA) in their blood and urine. To identify the transporter mediating the translocation of 3OH-GA through membranes, kidney tissue of Gcdh-/- mice have been investigated because of its central role in urinary excretion of this metabolite. Using microarray analyses of kidney expressed genes in Gcdh-/- mice, several differentially expressed genes encoding transporter proteins were identified. Real-time polymerase chain reaction analysis confirmed the upregulation of the sodium-dependent dicarboxylate cotransporter 3 (NaDC3) and the organic cation transporter 2 (OCT2). Expression analysis of NaDC3 in Xenopus laevis oocytes by the two-electrode-voltage-clamp technique demonstrated the sodium-dependent translocation of 3OH-GA with a K (M) value of 0.95 mM. Furthermore, tracer flux measurements in Chinese hamster ovary cells overexpressing OCT2 showed that 3OH-GA inhibited significantly the uptake of methyl-4-phenylpyridinium, whereas 3OH-GA is not transported by OCT2. The data demonstrate for the first time the membrane translocation of 3OH-GA mediated by NaDC3 and the cis-inhibitory effect on OCT2-mediated transport of cations. PMID- 17356848 TI - Bias in toxicology. AB - The potential for bias, i.e., influences that cause results to deviate systematically from the truth is substantial both in toxicological research and in the performance of standardized toxicological testing. In this contribution, major potential sources of bias in toxicological research and testing are identified. Due to the lack of empirical studies of bias in toxicology, very little is known about its prevalence and impact. Areas to consider for such studies are pointed out, and it is suggested that such investigations should be given priority. PMID- 17356846 TI - Roles of PPARs on regulating myocardial energy and lipid homeostasis. AB - Myocardial energy and lipid homeostasis is crucial for normal cardiac structure and function. Either shortage of energy or excessive lipid accumulation in the heart leads to cardiac disorders. Peroxisome proliferator-activated receptors (PPARalpha, -beta/delta and -gamma), members of the nuclear receptor transcription factor superfamily, play important roles in regulating lipid metabolic genes. All three PPAR subtypes are expressed in cardiomyocytes. PPARalpha has been shown to control transcriptional expression of key enzymes that are involved in fatty acid (FA) uptake and oxidation, triglyceride synthesis, mitochondrial respiration uncoupling, and glucose metabolism. Similarly, PPARbeta/delta is a transcriptional regulator of FA uptake and oxidation, mitochondrial respiration uncoupling, and glucose metabolism. On the other hand, the role of PPARgamma on transcriptional regulation of FA metabolism in the heart remains obscure. Therefore, both PPARalpha and PPARbeta/delta are important transcriptional regulators of myocardial energy and lipid homeostasis. Moreover, it appears that the heart needs to have two PPAR subtypes with seemingly overlapping functions in maintaining myocardial lipid and energy homeostasis. Further studies on the potential distinctive roles of each PPAR subtype in the heart should provide new therapeutic targets for treating heart disease. PMID- 17356849 TI - Development of a Richter syndrome with a monoclonal component from a true B-cell chronic lymphocytic leukemia (B-CLL) treated with fludarabine. PMID- 17356847 TI - Pro-protein convertases in intermediary metabolism: islet hormones, brain/gut hormones and integrated physiology. AB - Many peptide hormones implicated in the regulation of intermediary metabolism arise from larger precursors called prohormones. These precursors are cut into pieces by proprotein convertases, more precisely those called prohormone convertases (PCs) that cleave at the C terminus of basic doublets. The remaining basic amino acids are eliminated by a specialized carboxypeptidase, leading to the active hormone. This processing may provide, from a single precursor, several peptides with different biological activities depending on the site(s) of cleavage on the precursor. When the processing is tissue-specific, this mechanism allows to produce, from a single protein, different sets of hormones depending on the tissue considered, leading to novel regulatory processes. The archetype of such a pluripotent prohormone in the field of intermediary metabolism is pro glucagon that, when cut by PC1 in intestinal L cells, produces four different peptides with different specificities [glicentin, oxyntomodulin (OXM), glucagon like peptide-1, and glucagon-like peptide-2], whereas, when cut by PC2 in the alpha cells of the endocrine pancreas, glucagon is produced and, through the supplementary action of NRD convertase, a fragment of glucagon (miniglucagon) with original properties. PMID- 17356850 TI - 11C-imaging: methyl jasmonate moves in both phloem and xylem, promotes transport of jasmonate, and of photoassimilate even after proton transport is decoupled. AB - The long-distance transport and actions of the phytohormone methyl jasmonate (MeJA) were investigated by using the short-lived positron-emitting isotope 11C to label both MeJA and photoassimilate, and compare their transport properties in the same tobacco plants (Nicotiana tabacum L.). There was strong evidence that MeJA moves in both phloem and xylem pathways, because MeJA was exported from the labeled region of a mature leaf in the direction of phloem flow, but it also moved into other parts of the same leaf and other mature leaves against the direction of phloem flow. This suggests that MeJA enters the phloem and moves in sieve tube sap along with photoassimilate, but that vigorous exchange between phloem and xylem allows movement in xylem to regions which are sources of photoassimilate. This exchange may be enhanced by the volatility of MeJA, which moved readily between non-orthostichous vascular pathways, unlike reports for jasmonic acid (which is not volatile). The phloem loading of MeJA was found to be inhibited by parachloromercuribenzenesulfonic acid (PCMBS) (a thiol reagent known to inhibit membrane transporters), and by protonophores carbonyl cyanide 3 chlorophenylhydrazone (CCCP) and 2,4-dinitrophenol (DNP) suggesting proton co transport. MeJA was found to promote both its own transport and that of recent photoassimilate within 60 min. Furthermore, we found that MeJA can counter the inhibitory effect of the uncoupling agent, CCCP, on sugar transport, suggesting that MeJA affects the plasma membrane proton gradient. We also found that MeJA's action may extend to the sucrose transporter, since MeJA countered the inhibitory effects of the sulfhydryl reagent, PCMBS, on the transport of photoassimilate. PMID- 17356851 TI - Identification of expression profiles of tapping panel dryness (TPD) associated genes from the latex of rubber tree (Hevea brasiliensis Muell. Arg.). AB - Tapping panel dryness (TPD) occurrence in high latex yielding rubber tree (Hevea brasiliensis) is characterized by the partial or complete cessation of latex flow upon tapping leading to severe loss in natural rubber production around the world. The goal of this study was to identify genes whose mRNA transcript levels are differentially regulated in rubber tree during the onset of TPD. To isolate TPD responsive genes, two cDNA libraries (forward and reverse) from total RNA isolated from latex of healthy and TPD trees were constructed using suppression subtractive hybridization (SSH) method. In total, 1,079 EST clones were obtained from two cDNA libraries and screened by reverse Northern blot analysis. Screening results revealed that about 352 clones were differentially regulated and they were selected for sequencing. Based on the nucleotide sequence data, the putative functions of cDNA clones were predicted by BLASTX/BLASTN analysis. Among these, 64 were genes whose function had been previously identified while the remaining clones were genes with either unknown protein function or insignificant similarity to other protein/DNA/EST sequences in existing databases. RT-PCR analysis was carried out to validate the up-regulated genes from both the libraries. Among them, two genes were strongly down-regulated in TPD trees. The level of mRNA transcripts of these two genes was further examined by conventional Northern and RT-PCR analysis. Results indicated that the expression level of two genes was significantly lower in TPD trees compared to healthy trees. Many TPD associated genes were also up-regulated in TPD trees suggesting that they may be involved in triggering programmed cell death (PCD) during the onset of TPD syndrome. The results presented here demonstrate that SSH technique provides a powerful complementary approach for the identification of TPD related genes from rubber tree. PMID- 17356852 TI - Transcription of the singed-weak mutation of Drosophila melanogaster: elimination of P-element sequences by RNA splicing and repression of singed transcription in a P genetic background. AB - The dysgenesis-induced, hypermutable singed-weak allele has two incomplete P elements inserted in a head-to-head configuration in the 5' non-coding exon of the singed bristle locus of Drosophila melanogaster. In the presence of P transposase, each element excises to produce single element derivatives, singed extreme and singed-(+), that have either an extreme bristle or wild-type phenotype, respectively. In an M background, pseudo-wild-type transcripts are made that initiate at the singed promoter, read through the insertions, and are spliced to remove the P-element sequences and part of the 5' exon. The abundance of the pseudo-wild-type RNAs in pupae correlates with the bristle phenotype, being highest in singed-(+) and lowest in singed-extreme. Other RNAs are made that retain the insertions, or are truncated with respect to the downstream coding singed exons and have their 3' ends within the insertions. The mutants are female-fertile in an M background but sterile in a P background where little singed RNA can be detected. Transgenes containing either a complete P-element or an incomplete P-element known as KP impair the fertility of females carrying the singed-weak mutation, suggesting that the proteins encoded by these two widely distributed P-elements may be responsible for inhibiting transcription of singed weak in a P background. PMID- 17356853 TI - Spatial patterns of ectomycorrhizal fungal inoculum in arbuscular mycorrhizal barrens communities: implications for controlling invasion by Pinus virginiana. AB - Invasion of globally threatened ecosystems dominated by arbuscular mycorrhizal plants, such as the alkaline prairies and serpentine barrens of eastern North America, by species of ectomycorrhizal (ECM) pine (Pinus) seriously threatens the persistence, conservation, and ongoing restoration of these rare plant communities. Using Maryland serpentine barrens and an Ohio alkaline prairie complex as model systems, we tested the hypothesis that the invasiveness of Virginia pine (Pinus virginiana L.) into such communities is regulated by the spatial pattern of ECM fungal inoculum in the soil. ECM colonization of pine seedlings can occur by (1) hyphae growing from the roots of mature ECM pines colonizing nearby seedlings (contagion model), (2) pine seedlings being infected after germinating in open areas where spores are concentrated in feces of animals that have consumed sporocarps (centers of infection model), and (3) colonization from spores that are wind-dispersed across the landscape (background model). To test these models of dispersal of ECM fungal inoculum into these barrens, we used autocorrelation and spatially explicit mapping techniques (semivariance analysis and kriging) to characterize the distribution and abundance of ECM inoculum in soil. Our results strongly suggest that ECM fungi most often disperse into open barrens by contagion, thereby facilitating rapid pine colonization in an advancing front from mature pine forests bordering the barrens. Spatial patterns consistent with the centers of infection model were present but less common. Thus, current management techniques that rely on cutting and fire to reverse pine invasion may be ineffective because they do not kill or disrupt hyphal mats attached to mature roots of neighboring pines. Management alternatives are discussed. PMID- 17356854 TI - Exogenous systemin has a contrasting effect on disease resistance in mycorrhizal tomato (Solanum lycopersicum) plants infected with necrotrophic or hemibiotrophic pathogens. AB - A study was performed to determine the effect of the systemin polypeptide on the bio-protective effect of arbuscular mycorrhizal fungi (AMF) in tomato plants infected with Alternaria solani, Phytophthora infestans or P. parasitica. Before infection, tomato plants were colonized with two different AMF, Glomus fasciculatum or G. clarum. In addition, a group of inoculated plants was treated with systemin, just after emergence. The exogenous application of systemin marginally suppressed the resistance against A. solani leaf blight observed in G. fasciculatum mycorrhizal plants but significantly enhanced it in plants colonized with G. clarum. Systemin induced resistance to P. parasitica in leaves of G. fasciculatum mycorrhizal plants, in which AMF colonization alone was shown to have no protective effect. Conversely, none of the treatments led to resistance to root or stem rots caused by P. infestans or P. parasitica. The above effects did not correlate with changes in the activity levels of beta-1,3-glucanase (BG), chitinase (CHI), peroxidase (PRX), and phenylalanine ammonium lyase (PAL) in leaves of infected plants. However, they corroborated previous reports showing that colonization by AMF can lead to a systemic resistance response against A. solani. Systemic resistance to A. solani was similarly observed in non mycorrhizal systemin-treated plants, which, in contrast, showed increased susceptibility to P. infestans and P. parasitica. The results indicated that the pattern of systemic disease resistance conferred by mycorrhizal colonization was dependent on the AMF employed and could be altered by the exogenous application of systemin, by means of a still undefined mechanism. PMID- 17356855 TI - Is there an association between economic performance and public satisfaction in health care? AB - Earlier studies on the association between health systems' economic performance and public satisfaction were based on between-countries comparisons. This approach can be challenged as it ignores the fact that subjective measures like 'satisfaction' might be relative. Cohort analysis is a way of dealing with this issue as it focuses on within-countries comparisons. The association between change in satisfaction with health care systems and change in economic performance, determined by an output-orientated constant returns to scale DEA Malmquist model over the period 1995 to 2000/2002 using OECD data, is explored. The results show that a health care systems' economic performance is not associated with public satisfaction. PMID- 17356856 TI - Fetal counselling for congenital malformations. PMID- 17356857 TI - Are there predictive factors for the outcome of endoscopic treatment of grade III V vesicoureteral reflux with dextranomer/hyaluronic acid in children? AB - Dextranomer/hyaluronic acid (Dx/HA) copolymer has been used widely for the treatment of vesicoureteral reflux (VUR) in children since 2001. However, the factors that influence the outcome of injection therapy with Dx/HA have remained unclear. In this study, we retrospectively evaluated the outcomes in 101 consecutive children to determine the cure and to identify the factors that can impact treatment outcomes of Dx/HA injection. Endoscopic treatment with Dx/HA was performed in 133 ureters, in 101 patients with grade III-V VUR. Of the patients, 68 (67.3%) were girls and the mean age was 6.5 years. Before and after the treatment, the presence and grades of VUR were determined by voiding cystourethrograms. The patients' age, gender, laterality, preoperative reflux grade, ureteral duplication, morphology of ureteral orifice, renal hypoplasia and experience with surgery were assessed as predictive factors related to the success rates of Dx/HA injection therapy. The cure rates were 54.8% after the first injection, 66.9% after the second and 73.6% after the third injection. Patients with a high grade (grade IV or V), duplicated system, golf hole-shaped orifice and renal hypoplasia had significantly lower cure rates (P<0.05). Experience with the technique also correlated with the positive outcome of the procedure. New contralateral vesicoureteral reflux developed in five (7.2%) patients with unilateral VUR, and all of them resolved spontaneously during the first year of followup. No treatment-related significant complication was encountered. Although, endoscopic treatment of VUR with Dx/HA provides a high rate of success in children with medium or high grade VUR, treatment failure may be seen in some patients. However, we showed that endoscopic treatment with Dx/HA was effective in selected patients with grade V VUR, and we emphasize the need for further large-scale studies to confirm our findings. PMID- 17356858 TI - Diminished quality of life in patients with cancer correlates with tryptophan degradation. AB - PURPOSE: Quality of life (QoL) is frequently impaired in patients suffering from malignant disease. Disturbed metabolism of neurotransmitter serotonin might be crucially involved, and serotonin-precursor tryptophan is degraded during pro inflammatory immune response. In this study, we compared QoL and fatigue self rating scores of patients with various types of malignancy with tryptophan metabolic changes and immune activation status. METHODS: Venous blood was collected from 146 patients with gastrointestinal tumors (n = 43), hematological malignancy (n = 40), gynecological neoplasms (n = 26), lung cancer (n = 20) and from tumors of other localization (n = 17). RESULTS: QoL was significantly reduced in patients suffering from progressive tumor disease in comparison to stable or remitting disease, also feeling of fatigue was increased (both P < 0.001). Serum tryptophan concentrations were lower in patients with progressive disease (P < 0.01), and decreased tryptophan concentrations were related to decreased QoL (r(s) = 0.256, P < 0.01) and increased fatigue (r(s) = -0.179; P < 0.05). Concentrations of tryptophan and kynurenine and the kynurenine to tryptophan ratio were predictive for impaired QoL and increased fatigue in univariate regression analysis, in multivariate analysis higher ESR and neopterin concentration in combination with stage of disease predicted QoL deterioration. CONCLUSIONS: Results suggest that immune-mediated tryptophan degradation may contribute to cancer-induced QoL deterioration. PMID- 17356859 TI - [Base excess. Parameter with exceptional clinical significance]. AB - The base excess of blood (BE) plays an important role in the description of the acid-base status of a patient and is gaining in clinical interest. Apart from the Quick test, the age, the injury severity score and the Glasgow coma scale, the BE is becoming more and more important to identify, e. g. the risk of mortality for patients with multiple injuries. According to Zander the BE is calculated using the pH, pCO(2), haemoglobin concentration and the oxygen saturation of haemoglobin (sO(2)). The use of sO(2 )allows the blood gas analyser to determine only one value of BE, independent of the type of blood sample analyzed: arterial, mixed venous or venous. The BE and measurement of the lactate concentration (cLac) play an important role in diagnosing critically ill patients. In general, the change in BE corresponds to the change in cLac. If DeltaBE is smaller than DeltacLac the reason could be therapy with HCO(3)(-) but also with infusion solutions containing lactate. Physician are very familiar with the term BE, therefore, knowledge about an alkalizing or acidifying effect of an infusion solution would be very helpful in the treatment of patients, especially critically ill patients. Unfortunately, at present the description of an infusion solution with respect to BE has not yet been accepted by the manufacturers. PMID- 17356860 TI - [Angioedema caused by C1-esterase inhibitor deficiency or ACE inhibitors?]. AB - A 49-year-old woman was admitted to the intensive care ward with increasing shortness of breath due to a massive soft tissue swelling of the neck and face and a marked macroglossia. Similar symptoms were already observed earlier in the patient as well as her father, although such symptoms were never as dramatic as they were on this occasion. The patient was intubated bronchoscopically and treated unsuccessfully with cortisone, fresh plasma und C1-esterase inhibitor. The patient only first reported intake of an ACE inhibitor a few days after the acute episode, which was most probably the causative factor given that serum C1 and C4 complement factors were almost normal. PMID- 17356861 TI - [Clinical aspects of packed red cell transfusion. Lessons learned from Jehovah's Witnesses?]. AB - With the decreased risk of homologous blood transfusions, the costs of blood products have become increasingly important for hospitals with major surgical procedures and oncologic treatment. It is well established from clinical physiology that a hemoglobin concentration (cHb) lower than 6.21 mmol/l (10 g/dl) is enough to serve the oxygen demand of the tissues, but transfusion of erythrocytes is still liberally carried out. Data obtained from Jehovah's Witnesses, who categorically refuse blood transfusions, demonstrate that they have an outcome similar to patients who are transfused. The lessons we have learned from Jehovah's Witnesses should result in an emotionless discussion, and a reduction in transfusion requirements. PMID- 17356862 TI - [Antiphospholipid syndrome 2007. Current aspects of laboratory diagnostics and their therapeutic consequences]. AB - Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent vascular thrombosis and loss of pregnancy in association with the presence of antiphospholipid antibodies (APA) detectable as lupus anticoagulants, anticardiolipin antibodies or anti-beta2 glycoprotein I antibodies. The pathophysiological importance of APA in APS is accepted, however, the mechanisms leading to thrombosis are likely to be multifactorial and are so far unclear. Without a prior thrombosis, the risk of developing a new thrombosis in healthy patients with APA is slightly increased (<1% per year). However, the risk of a recurrent thrombosis increases considerably (>10% per year) in patients with a history of thrombosis without anticoagulation. The careful and correct identification of patients with APS is important because prophylactic anticoagulation can reduce the risk of recurrent thrombotic events, and during pregnancy can improve fetal and maternal outcome. PMID- 17356863 TI - Chromosomal location of Pm35, a novel Aegilops tauschii derived powdery mildew resistance gene introgressed into common wheat (Triticum aestivum L.). AB - A single gene controlling powdery mildew resistance was identified in the North Carolina germplasm line NC96BGTD3 (NCD3) using genetic analysis of F(2) derived lines from a NCD3 X Saluda cross. Microsatellite markers linked to this Pm gene were identified and their most likely order was Xcfd7, 10.3 cM, Xgdm43, 8.6 cM, Xcfd26, 11.9 cM, Pm gene. These markers and the Pm gene were assigned to chromosome 5DL by means of Chinese Spring Nullitetrasomic (Nulli5D-tetra5A) and ditelosomic (Dt5DL) lines. A detached leaf test showed a distinctive disease reaction to six pathogen isolates among the NCD3 Pm gene, Pm2 (5DS) and Pm34 (5DL). An allelism test showed independence between Pm34 and the NCD3 Pm gene. Together, the tests provided strong evidence for the presence of a novel Pm gene in NCD3, and this gene was designated Pm35. PMID- 17356864 TI - Bayesian association mapping of multiple quantitative trait loci and its application to the analysis of genetic variation among Oryza sativa L. germplasms. AB - One way to use a crop germplasm collection directly to map QTLs without using line-crossing experiments is the whole genome association mapping. A major problem with association mapping is the presence of population structure, which can lead to both false positives and failure to detect genuine associations (i.e., false negatives). Particularly in highly selfing species such as Asian cultivated rice, high levels of population structure are expected and therefore the efficiency of association mapping remains almost unknown. Here, we propose an approach that combines a Bayesian method for mapping multiple QTLs with a regression method that directly incorporates estimates of population structure. That is, the effects due to both multiple QTLs and population structure were included in our statistical model. We evaluated the efficiency of our approach in simulated- and real-trait analyses of a rice germplasm collection. Simulation analyses based on real marker data showed that our model could suppress both false-positive and false-negative rates and the error of estimation of genetic effects over single QTL models, indicating that our model has statistically desirable attributes over single QTL models. As real traits, we analyzed the size and shape of milled rice grains and found significant markers that may be linked to QTLs reported previously. Association mapping should have good prospects in highly selfing species such as rice if proper methods are adopted. Our approach will be useful for the whole genome association mapping of various selfing crop species. PMID- 17356865 TI - Identification of QTL for resistance and susceptibility to Stagonospora meliloti in autotetraploid lucerne. AB - In eastern Australia and California, USA, one of the major lethal fungal diseases of lucerne (Medicago sativa) is Stagonospora root and crown rot, caused by Stagonospora meliloti. Quantitative trait loci (QTL) involved in resistance and susceptibility to S. meliloti were identified in an autotetraploid lucerne backcross population of 145 individuals. Using regression analysis and interval mapping, we detected one region each on linkage groups 2, 6 and 7 that were consistently associated with disease reaction to S. meliloti in two separate experiments. The largest QTL on linkage group 7, which is associated with resistance to S. meliloti, contributed up to 17% of the phenotypic variation. The QTL located on linkage group 2, which is potentially a resistance allele in repulsion to the markers for susceptibility to S. meliloti, contributed up to 8% of the phenotypic variation. The QTL located on linkage group 6, which is associated with susceptibility to S. meliloti, contributed up to 16% of the phenotypic variation. A further two unlinked markers contributed 5 and 8% of the phenotypic variation, and were detected in only one experiment. A total of 517 simple sequence repeat (SSR) markers from Medicago truncatula were screened on the parents of the mapping population. Only 27 (6%) SSR markers were polymorphic and could be incorporated into the autotetraploid map of M. sativa. This allowed alignment of our M. sativa linkage map with published M. truncatula maps. The markers linked to the QTL we have reported will be useful for marker assisted selection for partial resistance to S. meliloti in lucerne. PMID- 17356866 TI - Identification of QTL for reaction to three races of Colletotrichum trifolii and further analysis of inheritance of resistance in autotetraploid lucerne. AB - Anthracnose, caused by Colletotrichum trifolii, is one of the most serious diseases of lucerne worldwide. The disease is managed through deployment of resistant cultivars, but new pathotypes present a challenge to the successful implementation of this strategy. This paper reports the genetic map locations of quantitative trait loci (QTL) for reaction to races 1, 2 and 4 of C. trifolii in a single autotetraploid lucerne clone, designated W126 from the Australian cv. Trifecta. Resistance was mapped in a backcross population of 145 individuals, and reaction was assessed both by spray and injection inoculation of stems. Resistance to injection inoculation with races 1 and 4 was incompletely dominant and closely linked (phenotypic markers 2.2 cM apart); these resistances mapped to a linkage group homologous to Medicago truncatula linkage group 8. When the spray inoculation data were subjected to QTL analysis, the strongest QTL for resistance was located on linkage group 8; six QTL were identified for race 1 and four for race 4. Resistance to race 2 was incompletely recessive; four QTL were identified and these include one QTL on linkage group 4 that was also identified for race 1. Modelling of the interactions between individual QTL and marker effects allowed a total of 52-63% of the phenotypic variation to be described for each of the different races. These markers will have value in breeding lucerne, carrying multiple sources of resistance to the three known races of C. trifolii. PMID- 17356867 TI - Characterization and mapping of cryptic alien introgression from Aegilops geniculata with new leaf rust and stripe rust resistance genes Lr57 and Yr40 in wheat. AB - Leaf rust and stripe rust are important foliar diseases of wheat worldwide. Leaf rust and stripe rust resistant introgression lines were developed by induced homoeologous chromosome pairing between wheat chromosome 5D and 5M(g) of Aegilops geniculata (U(g)M(g)). Characterization of rust resistant BC(2)F(5) and BC(3)F(6) homozygous progenies using genomic in situ hybridization with Aegilops comosa (M) DNA as probe identified three different types of introgressions; two cytologically visible and one invisible (termed cryptic alien introgression). All three types of introgression lines showed similar and complete resistance to the most prevalent pathotypes of leaf rust and stripe rust in Kansas (USA) and Punjab (India). Diagnostic polymorphisms between the alien segment and recipient parent were identified using physically mapped RFLP probes. Molecular mapping revealed that cryptic alien introgression conferring resistance to leaf rust and stripe rust comprised less than 5% of the 5DS arm and was designated T5DL.5DS 5M(g)S(0.95). Genetic mapping with an F(2)population of Wichita x T5DL.5DS 5M(g)S(0.95) demonstrated the monogenic and dominant inheritance of resistance to both diseases. Two diagnostic RFLP markers, previously mapped on chromosome arm 5DS, co-segregated with the rust resistance in the F(2) population. The unique map location of the resistant introgression on chromosome T5DL.5DS-5M(g)S(0.95) suggested that the leaf rust and stripe rust resistance genes were new and were designated Lr57 and Yr40. This is the first documentation of a successful transfer and characterization of cryptic alien introgression from Ae. geniculata conferring resistance to both leaf rust and stripe rust in wheat. PMID- 17356868 TI - Genome mapping of white clover (Trifolium repens L.) and comparative analysis within the Trifolieae using cross-species SSR markers. AB - Allotetraploid white clover (Trifolium repens L.), a cool-season perennial legume used extensively as forage for livestock, is an important target for marker assisted breeding. A genetic linkage map of white clover was constructed using simple sequence repeat (SSR) markers based on sequences from several Trifolieae species, including white clover, red clover (T. pratense L.), Medicago truncatula (Gaertn.) and soybean (Glycine max L.). An F(1) population consisting of 179 individuals, from a cross between two highly heterozygous genotypes, GA43 and Southern Regional Virus Resistant, was used for genetic mapping. A total of 1,571 SSR markers were screened for amplification and polymorphism using DNA from two parents and 14 F(1)s of the mapping population. The map consists of 415 loci amplified from 343 SSR primer pairs, including 83 from white clover, 181 from red clover, 77 from M. truncatula, and two from soybean. Linkage groups for all eight homoeologous chromosome pairs of allotetraploid white clover were detected. Map length was estimated at 1,877 cM with 87% genome coverage. Map density was approximately 5 cM per locus. Segregation distortion was detected in six segments of the genome (homoeologous groups A1, A2, B1, B2, C1, and D1). A comparison of map locations of markers originating from white clover, red clover, and alfalfa (M. sativa L.) revealed putative macro-colinearity between the three Trifolieae species. This map can be used to link quantitative trait loci with SSR markers, and accelerate the improvement of white clover by marker-assisted selection and breeding. PMID- 17356869 TI - Fine mapping of the Pc locus of Sorghum bicolor, a gene controlling the reaction to a fungal pathogen and its host-selective toxin. AB - Milo disease in sorghum is caused by isolates of the soil-borne fungus Periconia circinata that produce PC-toxin. Susceptibility to milo disease is conditioned by a single, semi-dominant gene, termed Pc. The susceptible allele (Pc) converts to a resistant form (pc) spontaneously at a gametic frequency of 10(-3) to 10(-4). A high-density genetic map was constructed around the Pc locus using DNA markers, allowing the Pc gene to be delimited to a 0.9 cM region on the short arm of sorghum chromosome 9. Physically, the Pc-region was covered by a single BAC clone. Sequence analysis of this BAC revealed twelve gene candidates. Several of the predicted genes in the region are homologous to disease resistance loci, including one NBS-LRR resistance gene analogue that is present in multiple tandem copies. Analysis of pc isolines derived from Pc/Pc sorghum suggests that one or more members of this NBS-LRR gene family are the Pc genes that condition susceptibility. PMID- 17356870 TI - Xanthan is not essential for pathogenicity in citrus canker but contributes to Xanthomonas epiphytic survival. AB - Xanthan-deficient mutants of Xanthomonas axonopodis pv. citri, the bacterium responsible for citrus canker, were generated by deletion and marker exchange of the region encoding the carboxy-terminal end of the first glycosyltransferase, GumD. Mutants of gumD did not produce xanthan and remained pathogenic in citrus plants to the same extent as wild-type bacteria. The kinetics of appearance of initial symptoms, areas of plant material affected, and growth of bacteria inside plant tissue throughout the disease process were similar for both wild-type and mutant inoculations. Moreover, exopolysaccharide deficiency did not impair the ability of the bacteria to induce hypersensitive response on non-host plants. Apart from variations in phenotypic aspects, no differences in growth or survival under different stress conditions were observed between the xanthan-deficient mutant and wild-type bacteria. However, gumD mutants displayed impaired survival under oxidative stress during stationary phase as well as impaired epiphytic survival on citrus leaves. Our results suggest that xanthan does not play an essential role in citrus canker at the initial stages of infection or in the incompatible interactions between X. axonopodis pv. citri and non-host plants, but facilitates the maintenance of bacteria on the host plant, possibly improving the efficiency of colonization of distant tissue. PMID- 17356871 TI - Computational modeling of factors that modulate the unique FeNO bonding in {FeNO}(6) heme-thiolate model complexes. AB - A density functional theory account of the changes in FeNO bonding that occur in response to both bonded and nonbonded structural perturbations is reported for a series of {FeNO}(6) heme-thiolate model complexes. Using [Fe(porphine)(SCH(3))NO] as the reference complex, we constructed models to mimic equatorial (cis), distal, and proximal influences of protein environments. Overall, the results from these calculations reveal that the Fe-NO and N-O bond strengths change in the same direction upon variations in structure and environment. These bonding changes are manifested in unique direct correlations between the Fe-NO and N-O vibrational frequencies and bond lengths, as evidenced by their positive slopes (slopes of the familiar inverse or backbonding correlations are negative). The electronic origin of the direct correlations appears to derive from the electron density distribution in high-energy molecular orbitals. This variability modulates the FeNO antibonding character throughout the triatomic FeNO moiety. The results of this study suggest that the stabilities and reactivities of {FeNO}(6) centers in heme-thiolate enzymes can be modulated over a significant range through a variety of bonded and nonbonded means. PMID- 17356872 TI - Cellular activity of Rev response element RNA targeting metallopeptides. AB - The cellular chemistry of metallopeptide complexes designed to target and inactivate an HIV Rev response element (RRE) RNA sequence in vivo has been evaluated by use of an efficient cellular fluorescence assay. Transcribed messenger RNA encoding the green fluorescent protein (GFP) that includes a target RNA sequence is sensitive to cleavage chemistry mediated by metal derivatives of GGH(G)(x)TRQARRNRR RRWRERQR (x = 0, 1, 2, 4, 6). This results in a significant decrease in expression of GFP that can be quantified by fluorimetry. Optimal inactivation of the target RRE RNA was achieved with linkers where x = 0 or 1. Neither the Rev control peptide (lacking metal-binding or linker sequences) nor the metal-binding motif alone had any significant effect. Consequently, both the cleavage motif and the RNA targeting motif are essential to promote cellular cleavage of the target RRE RNA. However, target inactivation was also observed in experiments with metal-free peptide, consistent with recruitment of intracellular metal ion by the peptide following cellular uptake, with subsequent cleavage of the RRE target RNA. The RRE RNA cleavage activities of metallopeptide complexes were further confirmed by in vitro experiments and mammalian cell assays. PMID- 17356873 TI - [Botulinum toxin treatment in the head and neck region: current aspects, developments, and problems]. AB - Some interesting developments, aspects, and problems concerning botulinum toxin treatment of disorders of the head and neck region have recently been reported. These new approaches are discussed in this review. They include applications into mimic muscles (prevention of scar formation, treatment of depressions), into laryngeal muscles, and into the upper esophagus. In addition, treatment of different forms of headache and tinnitus as well as applications in the autonomic nervous system are addressed. Some of these options will shortly be put into clinical use, while others have to be checked further in clinical studies. PMID- 17356874 TI - [Accelerated hyperfractionated radiotherapy with concurrent chemotherapy in locally advanced nasopharyngeal carcinomas]. AB - BACKGROUND: The excellent results yielded by hyperfractionated and accelerated radiotherapy associated with concurrent chemotherapy in locally advanced oropharyngeal and hypopharyngeal carcinomas led to investigation of this therapeutic regimen in nasopharyngeal carcinomas also. METHODS: Thirty-five patients with stage III and IV nasopharyngeal carcinomas received accelerated hyperfractionated radiotherapy with concurrent chemotherapy (5-FU, mitomycin C + leucovorin). In the first 3 weeks of treatment five 2-Gy doses per week were delivered to the primary tumour and regional lymph nodes. The fractionation was then accelerated, with 1.4 Gy given twice daily until a total dose of 72 Gy had been administered. RESULTS: The overall objective response rate was 100%. The median follow-up period was 71 months. Salvage surgery of the lymph nodes was performed in 10 patients, revealing vital tumour tissue in 6 of these. The actuarial 5-year local control rate was 64% (95%CI: 47-81%), while overall actuarial survival at 5 years was 70% (95%CI: 53-86%). CONCLUSION: Hyperfractionated accelerated radiotherapy with concurrent chemotherapy is effective and feasible in locally advanced nasopharyngeal carcinoma. PMID- 17356875 TI - [Integration of the active middle ear implant Vibrant Soundbridge in total auricular reconstruction]. AB - BACKGROUND: Patients with high-grade microtia and atresia require a sophisticated and specific treatment. Apart from the plastic reconstruction of the auricle, in some cases hearing rehabilitation is medically indicated or is desired by the patients. The long-term results of simultaneous middle ear reconstruction with tympanoplasty are often inadequate owing to a persisting air-bone gap, and new techniques in hearing rehabilitation are needed for these patients. METHODS: We present three cases of unilateral atresia to illustrate a combined approach integrating hearing rehabilitation using the active middle ear implant Vibrant Soundbridge (VSB) into plastic auricular reconstruction. The VSB was attached to the stapes suprastructure via the titanium clip in two of these cases and in the third case a subfacial approach was used to attach it directly to the membrane of the round window. RESULTS: The air-bone gap was reduced to 17 dB, 14 dB and 0.25 dB HL. In free-field speech recognition tests at 65 dB SPL the patients achieved 100%, 90% and 100% recognition with the activated implant. No postoperative complications such as facial nerve paresis, vertigo or inner ear damage were found. CONCLUSIONS: The integration of active middle ear implants in auricular reconstruction opens up a new approach in complete hearing rehabilitation. The additional implantation of the VSB does not have any negative effect on the healing process or the cosmetic outcome of the auricular reconstruction. PMID- 17356876 TI - Body mass estimations for Plateosaurus engelhardti using laser scanning and 3D reconstruction methods. AB - Both body mass and surface area are factors determining the essence of any living organism. This should also hold true for an extinct organism such as a dinosaur. The present report discusses the use of a new 3D laser scanner method to establish body masses and surface areas of an Asian elephant (Zoological Museum of Copenhagen, Denmark) and of Plateosaurus engelhardti, a prosauropod from the Upper Triassic, exhibited at the Paleontological Museum in Tubingen (Germany). This method was used to study the effect that slight changes in body shape had on body mass for P. engelhardti. It was established that body volumes varied between 0.79 m(3) (slim version) and 1.14 m(3) (robust version), resulting in a presumable body mass of 630 and 912 kg, respectively. The total body surface areas ranged between 8.8 and 10.2 m(2), of which, in both reconstructions of P. engelhardti, approximately 33% account for the thorax area alone. The main difference between the two models is in the tail and hind limb reconstruction. The tail of the slim version has a surface area of 1.98 m(2), whereas that of the robust version has a surface area of 2.73 m(2). The body volumes calculated for the slim version were as follows: head 0.006 m(3), neck 0.016 m(3), fore limbs 0.020 m(3), hind limbs 0.08 m(3), thoracic cavity 0.533 m(3), and tail 0.136 m(3). For the robust model, the following volumes were established: 0.01 m(3) head, neck 0.026 m(3), fore limbs 0.025 m(3), hind limbs 0.18 m(3), thoracic cavity 0.616 m(3), and finally, tail 0.28 m(3). Based on these body volumes, scaling equations were used to assess the size that the organs of this extinct dinosaur have. PMID- 17356877 TI - Abnormal APP processing in platelets of patients with Alzheimer's disease: correlations with membrane fluidity and cognitive decline. AB - RATIONALE: Previous studies have implicated platelet amyloid precursor protein (APP) as a candidate biomarker for Alzheimer's disease (AD). Platelets contain more than 95% of the circulating APP and enclose the enzymatic machinery for the APP metabolism yielding both soluble APP and amyloid-beta peptides. OBJECTIVES: The objective of this study is to compare the ratio of 130- to 110-kDa fragments of APP in platelets from patients with AD, mild cognitive impairment (MCI), and elderly controls. MATERIALS AND METHODS: After subjects were grouped according to diagnosis, APP ratio in platelets was evaluated by means of Western blot analysis. RESULTS: The APP ratio was significantly lower in AD patients (1.01 +/- 0.21) as compared to controls (1.24 +/- 0.21, p = 0.001) and MCI patients (1.18 +/- 0.21, p = 0.027), but no significant differences were found between MCI and controls (p = 0.904). In addition, we found positive correlations between the APP ratio and 1,6-diphenyl-1,3,5-hexatriene anisotropy (r = 0.3, p = 0.01), as well as with certain parameters of cognitive decline, namely, the mini-mental state examination score (r = 0.33, p = 0.003), the total Cambridge cognitive test (CAMCOG) score (r = 0.37, p = 0.001), and the score on the memory subscale of the CAMCOG (r = 0.38, p = 0.001). CONCLUSIONS: The pattern of platelet APP fragments was altered in patients with AD but not in patients with MCI. The alteration of APP fragments was correlated with membrane fluidity and the cognitive decline. PMID- 17356878 TI - Spinal cord ionotropic glutamate receptors function in formalin-induced nociception in preweaning rats. AB - RATIONALE: Neonates respond to noxious stimuli at or before birth, but the organization of nociceptive systems changes well into postnatal life. It is unknown how nociceptive information is processed in the immature animal and, specifically, whether noxious stimulation is transmitted by glutamatergic circuits, known to play an important role in nociception in the adult. Both N methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are found within the neonatal spinal cord, but in immature form, and when they become involved in pain processing in vivo is not known. OBJECTIVES: The objective was to determine the age-related changes in the involvement of spinal NMDA and AMPA receptors in formalin-induced nociception during early life. Because the formalin test provides a measure of immediate nociceptive responding (first phase) and of peripheral and central sensitization (second phase), a second aim was to determine if there is specificity of the effects to either phase. MATERIALS AND METHODS: NMDA antagonists (MK801, AP5) or an AMPA antagonist (YM872) was administered intrathecally, and pups were assessed in the formalin test behaviorally and by Fos expression within the spinal cords of 3-, 10-, and 21-day-old rats. RESULTS: The NMDA antagonists attenuated formalin-induced behavioral responses at the youngest age tested with some selectivity for the second phase of responding. MK-801 did not induce motor impairment at any age. YM872 also attenuated formalin-induced nociceptive responses at all ages throughout the test session, although there was some motor impairment in the 3-day-old subjects. Spinal administration of either YM872 or MK 801 reduced Fos expression in the spinal cord at all ages. CONCLUSIONS: These data suggest that spinal NMDA and AMPA receptor are functional and involved in formalin-induced nociception throughout development. PMID- 17356880 TI - Effect of antibiotic loading on the shear strength at the stem-cement interface (Shear strength of antibiotic loaded cement). AB - The purpose of this study was to investigate the effects of addition of antibiotics into cement powder on the shear properties of the cement-metal interface. The approach involved adding 800 mg of teicoplanin to 40 g bone cement powder in the t-800 group, 1,600 mg teicoplanin in the t-1,600 group, and no antibiotic in the control group. Industrially prepared bone cement containing 500 mg of gentamicin was used as group g-500. Each group consisted of ten samples. Cement-metal interfaces were produced using metal discs with porous surfaces (1 microm) and templates at the third minute. Shear stability of specimens was measured in a material testing machine. The ANOVA test was used for comparison between the mean shear results of each group. Results showed that mean shear stress to failure values were 12.28+/-3.35 MPa for the control group, 11.72+/ 3.09 MPa for the t-800 group, 13.25+/-2.36 MPa for the t-1,600 group and 13.09+/ 2.58 MPa for the g-500 group. No statistically significant differences were found between results of the groups. Results of the study have proven that addition of 1,600 mg of teicoplanin or 500 mg gentamycin in 40 g of bone cement does not decrease the shear strength at the cement-metal interface significantly on the day of application. PMID- 17356879 TI - Species-specific evolution of the FcR family in endothermic vertebrates. AB - In primates and rodents, the extended FcR family is comprised of three subsets: classical FcRs, structurally diverse cell surface receptors currently designated FCRL1-FCRL6, and intracellular proteins FCRLA and FCRLB. Using bioinformatic analysis, we revealed the FcR-like genes of the same three subsets in the genome of dog, another representative of placental mammals, and in the genome of short tailed opossum, a representative of marsupials. In contrast, a single FcR-like gene was found in the current version of the chicken genome. This in silico finding was confirmed by the gene cloning and subsequent Southern blot hybridization. The chicken FCRL gene encodes a cell surface receptor with the extracellular region composed of four Ig-like domains of the D1-, D2-, D3-, and D4-subtypes. The gene is expressed in lymphoid and non-lymphoid tissues. Phylogenetic analysis of the mammalian and chicken genes suggested that classical FcRs, FCRLA, and FCRLB emerged after the mammalian-avian split but before the eutherian-marsupial radiation. The data obtained show that the repertoire of the classical FcRs and surface FcR-like proteins in mammalian species was shaped by an extensive recombination process, which resulted in domain shuffling and species-specific gain and loss of distinct exons or entire genes. PMID- 17356882 TI - Subclinical impairment of arterial mechanics in systemic lupus erythematosus identified by arterial waveform analysis. AB - Structural and functional changes in wall and endothelial components of arterial blood vessels underlie the accelerated vascular disease progression in systemic lupus erythematosus (SLE). Using pulse contour analysis we sought to determine if subclinical vascular abnormalities could be identified in a well-characterised cohort of patients with SLE who had no increase in traditional cardiovascular risk factors. Radial artery pressure waveforms were obtained by applanation tonometry and pressure envelopes were analysed by descriptive and model-based approaches. Waveshape morphology was quantified by a novel eigenvector approach and model-based compliance indices of the large arteries (C1, capacitative arterial compliance) and small arteries (C2, reflective arterial compliance) were derived using a third-order four-element modified Windkessel model. Data were recorded from 30 patients with SLE (mean age 44 +/- 7 years and mean SLAM-R 10 +/ 4) and 19 age-matched control subjects. Significant differences in the lower frequency sinusoidal components of the pressure waveforms were evident between groups (P < 0.05). Both C1 and C2 were significantly reduced in patients with SLE: C1 mean +/- SD 13.5 +/- 4.0 ml/mmHg x 10 versus C1 17.5 +/- 4.8 ml/mmHg x 10 (P = 0.003 in patients vs. controls, respectively) and C2 5.2 +/- 3.4 ml/mmHg x 100 versus C2 9.4 +/- 2.8 ml/mmHg x 100 (P < 0.001 in patients vs. controls, respectively). In this group of SLE patients, without an excess of traditional cardiovascular risk factors and SLAM-R scores indicating mild disease, descriptive and model-based analysis of arterial waveforms identified vascular abnormalities at a preclinical stage. PMID- 17356883 TI - Plant sigma factors and their role in plastid transcription. AB - Plant sigma factors determine the promoter specificity of the major RNA polymerase of plastids and thus regulate the first level of plastome gene expression. In plants, sigma factors are encoded by a small family of nuclear genes, and it is not yet clear if the family members are functionally redundant or each paralog plays a particular role. The review presents the analysis of the information on plant sigma factors obtained since their discovery a decade ago and focuses on similarities and differences in structure and functions of various paralogs. Special attention is paid to their interaction with promoters, the regulation of their expression, and their role in the development of a whole plant. The analysis suggests that though plant sigma factors are basically similar, at least some of them perform distinct functions. Finally, the work presents the scheme of this gene family evolution in higher plants. PMID- 17356884 TI - Cell death in seedlings of the interspecific hybrid of Nicotiana gossei and N. tabacum; possible role of knob-like bodies formed on tonoplast in vacuolar collapse-mediated cell death. AB - Vacuolar collapse plays a direct role in the cell death of the interspecific hybrid of Nicotiana gossei Domin xN. tabacum L. which exhibits hybrid lethality at the seedling stage. We have previously reported that cell death in these seedlings began at the base of hypocotyls and spread throughout the plant (Mino et al. 2002). A light microscopic analysis revealed that the process involved disruption of the intra-cellular membranes, plasmolysis, and retraction of the wall of the cell in hypocotyls. A transmission electron microscopic analysis showed that there were several abnormal structures, i.e. knob-like bodies on the tonoplast and small vesicles in the cytoplasm, and the disintegration of the tonoplast, in the cells of seedlings grown at 26 degrees C. However, no such cytological defects were observed in the seedlings grown at 37 degrees C, at which temperature the expression of lethality was suppressed. The activity levels of vacuolar processing enzyme (VPE), which might be involved in the vacuolar collapse of plant cells, temporarily increased in the seedlings grown at 26 degrees C before apparent cell death proceeded, but it remained unchanged in the seedlings grown at 37 degrees C. Applications of acetyl-L: -tyrosyl-L: -valyl-L: alanyl-L: -aspart-1-aldehyde, an inhibitor for VPE, and cycloheximide to the seedlings suppressed VPE's activities, the formation of knob-like bodies on the tonoplast, and cell death. VPE might be involved in the structural anomalies on the tonoplast which lead to cell death triggered by vacuolar collapse in hybrid seedlings. PMID- 17356885 TI - Distal colonic Na(+) absorption inhibited by luminal P2Y(2) receptors. AB - Luminal P2 receptors are ubiquitously expressed in transporting epithelia. In steroid-sensitive epithelia (e.g., lung, distal nephron) epithelial Na(+) channel (ENaC)-mediated Na(+) absorption is inhibited via luminal P2 receptors. In distal mouse colon, we have identified that both, a luminal P2Y(2) and a luminal P2Y(4) receptor, stimulate K(+) secretion. In this study, we investigate the effect of luminal adenosine triphosphate/uridine triphosphate (ATP/UTP) on electrogenic Na(+) absorption in distal colonic mucosa of mice treated on a low Na(+) diet for more than 2 weeks. Transepithelial electrical parameters were recorded in an Ussing chamber. Baseline parameters: transepithelial voltage (V (te)): -13.7 +/- 1.9 mV (lumen negative), transepithelial resistance (R (te)): 24.1 +/- 1.8 Omega cm(2), equivalent short circuit current (I (sc)): -563.9 +/- 63.8 microA/cm(2) (n = 21). Amiloride completely inhibited I (sc) to -0.5 +/- 8.5 microA/cm(2). Luminal ATP induced a slowly on-setting and persistent inhibition of the amiloride-sensitive I (sc) by 160.7 +/- 29.7 microA/cm(2) (n = 12, NMRI mice). Luminal ATP and UTP were almost equipotent with IC(50) values of 10 microM and 3 microM respectively. In P2Y(2) knock-out (KO) mice, the effect of luminal UTP on amiloride-sensitve Na(+) absorption was absent. In contrast, in P2Y(4) KO mice the inhibitory effect of luminal UTP on Na(+) absorption remained present. Semiquantitative polymerase chain reaction did not indicate regulation of the P2Y receptors under low Na(+) diet, but it revealed a pronounced axial expression of both receptors with highest abundance in surface epithelia. Thus, luminal P2Y(2) and P2Y(4) receptors and ENaC channels co-localize in surface epithelium. Intriguingly, only the stimulation of the P2Y(2) receptor mediates inhibition of electrogenic Na(+) absorption. PMID- 17356886 TI - The rise of [Na(+)] (i) during ischemia and reperfusion in the rat heart underlying mechanisms. AB - Intracellular Na(+) concentration ([Na(+)](i)) rises in the heart during ischemia, and on reperfusion, there is a transient rise followed by a return toward control. These changes in [Na(+)](i) contribute to ischemic and reperfusion damage through their effects on Ca(2+) overload. Part of the rise of [Na(+)](i) during ischemia may be caused by increased activity of the cardiac Na(+)/H(+) exchanger (NHE1), activated by the ischemic rise in [H(+)](i). In support of this view, NHE1 inhibitors reduce the [Na(+)](i) rise during ischemia. Another possibility is that the rise of [Na(+)](i) during ischemia is caused by Na(+) influx through channels. We have reexamined these issues by use of two different NHE1 inhibitors, amiloride, and zoniporide, in addition to tetrodotoxin (TTX), which blocks voltage-sensitive Na(+) channels. All three drugs produced cardioprotection after ischemia, but amiloride (100 microM) and TTX (300 nM) prevented the rise in [Na(+)](i) during ischemia, whereas zoniporide (100 nM) did not. Both amiloride and zoniporide prevented the rise of [Na(+)](i) on reperfusion, whereas TTX was without effect. In an attempt to explain these differences, we measured the ability of the three drugs to block Na(+) currents. At the concentrations used, TTX reduced the transient Na(+) current (I (Na)) by 11 +/- 2% while amiloride and zoniporide were without effect. In contrast, TTX largely eliminated the persistent Na(+) current (I (Na,P)) and amiloride was equally effective, whereas zoniporide had a substantially smaller effect reducing I (Na,P) to 41 +/- 8%. These results suggest that part of the effect of NHE1 inhibitors on the [Na(+)](i) during ischemia is by blockade of I (Na,P). The fact that a low concentration of TTX eliminated the rise of [Na(+)](i) during ischemia suggests that I (Na,P) is a major source of Na(+) influx in this model of ischemia. PMID- 17356887 TI - Genetic ancestry, population sub-structure, and cardiovascular disease-related traits among African-American participants in the CARDIA Study. AB - African-American populations are genetically admixed. Studies performed among unrelated individuals from ethnically admixed populations may be both vulnerable to confounding by population stratification, but offer an opportunity for efficiently mapping complex traits through admixture linkage disequilibrium. By typing 42 ancestry-informative markers and estimating genetic ancestry, we assessed genetic admixture and heterogeneity among African-American participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We also assessed associations between individual genetic ancestry and several quantitative and binary traits related to cardiovascular risk. We found evidence of population sub-structure and excess inter-marker linkage disequilibrium, consistent with recent admixture. The estimated group admixture proportions were 78.1% African and 22.9% European, but differed according to geographic region. In multiple regression models, African ancestry was significantly associated with decreased total cholesterol, decreased LDL-cholesterol, and decreased triglycerides, and also with increased risk of insulin resistance. These observed associations between African ancestry and several lipid traits are consistent with the general tendency of individuals of African descent to have healthier lipid profiles compared to European-Americans. There was no association between genetic ancestry and hypertension, BMI, waist circumference, CRP level, or coronary artery calcification. These results demonstrate the potential for confounding of genetic associations with some cardiovascular disease-related traits in large studies involving US African-Americans. PMID- 17356888 TI - Multifocal electroretinogram for assessing sun damage following the solar eclipse of 29 March 2006: multifocal electroretinography in solar maculopathy. AB - AIM: To evaluate the clinical findings and multifocal electroretinography results of cases with solar maculopathy due to eclipse watching. PATIENTS AND METHOD: Eight eyes of six patients (ages ranged 12-42) who presented to our clinic after the solar eclipse of 29 March 2006 were evaluated in the study. All patients underwent a full ophthalmologic examination and multifocal electroretinography (mfERG). RESULTS: Visual acuities at the initial examination were between 20/32 and 20/20; and at final examination between 20/25 and 20/20 respectively. Fundoscopic examination disclosed macular pigmentary changes in almost all patients. Fundus Fluorescein Angiography revealed a window defect in six eyes. The initial findings of the mfERG at the first visit showed a decrease in the P1 and N1 amplitudes of the central responses. The following mfERG recordings showed a recovery in central P1 and N1 amplitudes. CONCLUSION: Decrease in P1 and N1 amplitudes of central macular region can be detected by mfERG in patients with solar maculopathy. Follow-up mfERG test results may recover with the increase of visual acuity. PMID- 17356890 TI - Piezoelectric osteotomy: a new technique for bone surgery-advantages in craniofacial surgery. AB - INTRODUCTION: Ultrasonic bone cutting is a new surgical technique used in dentistry to section hard tissues without damaging adjacent soft tissues. We hypothesized that such a device could also be useful in craniofacial surgery, particularly during the removal of the superior orbital roof during craniofaciostenosis surgery. MATERIALS AND METHODS: An ultrasonic device was employed in different craniofacial surgical procedures: 1. to remove the superior orbital roof in 30 cases of craniofaciostenosis, 2. to perform a Le Fort III osteotomy for the treatment of Crouzon syndrome in two patients, 3. to cut the parietal and frontal bone in 30 cases of craniofaciostenosis. The integrity of soft tissues and surgical time was evaluated. RESULTS: Functional results were good without any soft tissue damage appreciated. The overall operative time, however, was increased. CONCLUSIONS: Piezosurgery is a new technical procedure, which can be advantageous for bone cutting in multiple situations with minimal to no damage in adjacent soft tissues. PMID- 17356889 TI - PET imaging in the surgical management of pediatric brain tumors. AB - OBJECTIVE: The present article illustrates whether positron-emission tomography (PET) imaging may improve the surgical management of pediatric brain tumors (PBT) at different steps. MATERIALS AND METHODS: Among 400 consecutive PBT treated between 1995 and 2005 at Erasme Hospital, Brussels, Belgium, we have studied with (18) F-2-fluoro-2-deoxy-D-glucose (FDG)-PET and/or L-(methyl-(11)C)methionine (MET)-PET and integrated PET images in the diagnostic workup of 126 selected cases. The selection criteria were mainly based on the lesion appearance on magnetic resonance (MR) sequences. Cases were selected when MR imaging showed limitations for (1) assessing the evolving nature of an incidental lesion (n = 54), (2) selecting targets for contributive and accurate biopsy (n = 32), and (3) delineating tumor tissue for maximal resection (n = 40). Whenever needed, PET images were integrated in the planning of image-guided surgical procedures (frame based stereotactic biopsies (SB), frameless navigation-based resections, or leksell gamma knife radiosurgery). RESULTS: Like in adults, PET imaging really helped the surgical management of the 126 children explored, which represented about 30% of all PBT, especially when the newly diagnosed brain lesion was (1) an incidental finding so that the choice between surgery and conservative MR follow up was debated, and (2) so infiltrative or ill-defined on MR that the choice between biopsy and resection was hardly discussed. Integrating PET into the diagnostic workup of these two selected groups helped to (1) take a more appropriate decision in incidental lesions by detecting tumor/evolving tissue; (2) better understand complex cases by differentiating indolent and active components of the lesion; (3) improve target selection and diagnostic yield of stereotactic biopsies in gliomas; (4) illustrate the intratumoral histological heterogeneity in gliomas; (5) provide additional prognostic information; (6) reduce the number of trajectories in biopsies performed in eloquent areas such as the brainstem or the pineal region; (7) better delineate ill-defined PBT infiltrative along functional cortex than magnetic resonance imaging (MRI); (8) increase significantly, compared to using MRI alone, the number of total tumor resection and the amount of tumor tissue removed in PBT for which a total resection is a key-factor of survival; (9) target the resection on more active areas; (10) improve detection of tumor residues in the operative cavity at the early postoperative stage; (11) facilitate the decision of early second-look surgery for optimizing the radical resection; (12) improve the accuracy of the radiosurgical dosimetry planning. CONCLUSIONS: PET imaging may improve the surgical management of PBT at the diagnostic, surgical, and post-operative steps. Integration of PET in the clinical workup of PBT inaugurates a new approach in which functional data can influence the therapeutic decision process. Although metabolic information from PET are valid and relevant for the clinical purposes, further studies are needed to assess whether PET-guidance may decrease surgical morbidity and increase children survival. PMID- 17356891 TI - Resistance of trichostrongyles to benzimidazoles in Italy: a first report in a goat farm with multiple and repeated introductions. AB - Anthelmintic resistance is widely distributed in small ruminants throughout the world. The extension of resistance seems lower in southern European countries and has not been reported previously in Italy. In the present study, resistance to benzimidazoles, levamisole and ivermectin was evaluated in a multi-breed goat farm of southern Italy. The farm had a history of repeated goat introductions from other flocks and a moderate regimen of anthelmintic treatments using alternatively the three above-mentioned drugs. Resistance of gastrointestinal strongyles was studied on the basis of faecal egg counts, egg hatch assay and necropsies. Resistance to anthelmintics was evidenced for benzimidazoles only, and Trichostrongylus colubriformis was the only resistant strongyle species. Single drug and single species resistance suggest that resistance is on its beginning and that measures for reducing the spread of resistance are of interest and should be promoted. PMID- 17356892 TI - Sequence analysis of the first internal transcribed spacer of rDNA supports the existence of the intermediate Fasciola between F. hepatica and F. gigantica in mainland China. AB - In the present study, a polymerase chain reaction-linked single-strand conformation polymorphism (PCR-SSCP) approach combined with DNA sequencing was used to characterise samples of Fasciola spp. from different host species and geographical locations in mainland China. The first internal transcribed spacer (ITS-1) of ribosomal DNA (rDNA) was amplified by PCR from individual Fasciola and analysed by SSCP. SSCP analyses displayed three different banding profiles that allowed the identification of all Fasciola samples examined into three groups: Fasciola hepatica, F. gigantica and the "intermediate" Fasciola. Then, the ITS-1 rDNA was sequenced from representative Fasciola samples, and analysis of the complete ITS-1 sequences supported the identification of all Fasciola samples by SSCP approach. The length of the ITS-1 sequences was 422 bp for all Fasciola samples sequenced. Although there was no variation in length or composition of the ITS-1 sequences among multiple specimens within each of the taxa, F. hepatica and F. gigantica differed by 1.2% in their ITS-1 sequences, whereas the "intermediate" Fasciola was unique, in which two different ITS-1 sequences exist in the rDNA array within a single Fasciola worm. One of the sequences is identical to that of F. hepatica, and the other is identical to that of F. gigantica. This study demonstrated that PCR-SSCP analysis of the ITS-1 rDNA followed by selective sequencing provides a reliable approach for the accurate identification of Fasciola spp., and also supports the existence of the "intermediate" Fasciola between F. hepatica and F. gigantica in mainland China. PMID- 17356893 TI - Comparison of Entamoeba histolytica DNA isolated from a cynomolgus monkey with human isolates. AB - Three protein-coding loci in DNA of an Entamoeba histolytica strain (EHMfas1) isolated from cynomolgus monkey (Macaca fascicularis) were sequenced; these loci corresponded to the genes for chitinase, the serine-rich E. histolytica protein (SREHP), and the 16 S-like small subunit ribosomal RNA (16S-like SSUrRNA). The nucleotide and deduced amino-acid sequences of chitinase and SREHP were compared with sequences from human isolates. EHMfas1 had several specific mutations in units in the polymorphic regions of the chitinase and SREHP loci, with some repetition of these mutated units. The sequence of the 16S-like SSUrRNA gene (16S like SSUrDNA) was compared with other Entamoeba species. In phylogenetic analysis, EHMfas1 was not categorized in the E. histolytica cluster but between E. histolytica and E. dispar. To our knowledge, this is the first molecular characterization of E. histolytica isolated from cynomolgus monkey, and our results indicate that EHMfas1 may be a subspecies of E. histolytica that infects cynomolgus monkey. PMID- 17356895 TI - Caspase-independent death of human osteosarcoma cells by flavonoids is driven by p53-mediated mitochondrial stress and nuclear translocation of AIF and endonuclease G. AB - Flavonoids have antioxidant and antitumor promoting effects. Rhus verniciflua Stokes (RVS) is a flavonoid-rich herbal medicine that has long been used in Korea as both a food additive and antitumor agent. It was previous reported that a purified flavonoid fraction prepared from RVS, herein named RCMF (the RVS chloroform-methanol fraction), inhibited the proliferation and induced apoptosis in human osteosarcoma (HOS) cells. This study examined the mechanisms involved in the RCMF-mediated apoptosis in HOS cells. RCMF was shown to be capable of inducing apoptosis in HOS cells by inducing p53 in the cells resulting in the decrease in Bcl-2 level, activation of Bax, and cytoplasmic release of cytochrome c, which led to the translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) into the nucleus. However, the RCMF-induced apoptosis was suppressed by transfecting the cells with antisense p53 oligonucleotides but not by treating them with a MAPK or caspase inhibitor. This suppression occurred through the regulation of Bcl-2 members as well as by preventing the nuclear translocation of the mitochondrial apoptogenic factors. Overall, it appears that p53-mediated mitochondrial stress and the nuclear translocation of AIF and EndoG are mainly required for the apoptosis induced by RCMF. PMID- 17356896 TI - Long-term follow-up results of postoperative radiation therapy for Cushing's disease. AB - OBJECTIVES: Radiotherapy is currently used in patients with residual or recurrent pituitary adenomas after surgery. However, there is little information of long term outcome of patients with Cushing's disease following radiotherapy. We assessed the long-term efficacy and toxicity of conventional radiotherapy in the control of Cushing's disease after unsuccessful transsphenoidal surgery. PATIENTS AND METHODS: Forty patients with Cushing's disease were treated with conventional external beam radiotherapy at our Institution between 1988 and 2002. The median age was 38. All patients received radiotherapy following unsuccessful surgery or at tumour recurrence to a dose of 45-50 Gy in 25-28 fractions. The persistence of active disease after surgery was diagnosed by the increased high plasma cortisol levels, high 24 h urinary cortisol levels and absence of cortisol suppression after administration of dexamethasone. RESULTS: The 5 and 10 year local tumour control was 93% and the 5 and 10 year survival was 97 and 95%. Normalization of plasma cortisol was seen in 28% of patients at 1 year, 73% at 3 years, 78% at 5 years and 84% at 10 years. The average timing to remission was 24 months. The most common side effect was hypopituitarism that increased progressively during the follow-up, being present in 62% and in 76% of patients at 5 and 10 years after RT. There were no other serious complications as radiation induced optic neuropathy or second tumours. CONCLUSION: Radiotherapy is effective in the long term tumour- and hormone hypersecretion control of ACTH-secreting pituitary adenomas, however with a high prevalence of hypopituitarism. At the moment, it remains an important treatment option after failure of surgery. PMID- 17356897 TI - Potential clinical role of FDG-PET in detecting sarcomatous transformation in von Recklinghausen's disease. PMID- 17356898 TI - Annual flooding and fish-mercury bioaccumulation in the environmentally impacted Rio Madeira (Amazon). AB - Regular annual flooding of the Amazonian rivers changes the aquatic environment affecting fish feeding strategies. The Rio Madeira has been greatly impacted by deforestation for agricultural projects, damming for a hydroelectric power plant, and alluvial gold extraction. We studied fish-Hg concentrations within defined weight ranges of representative species at the top of the food web, comparing high and low water seasons. Selected piscivorous species (Cichla spp, Hoplias malabaricus, Pinirampus pirinampu, Serrasalmus spp) showed a large variation of Hg concentrations but only "traira" (Hoplias malabaricus) showed a statistically significant difference between seasons. However, the bioaccumulation trends during high and low waters were similar for "tucunare" (Cichla spp) and "traira" (Hoplias malabaricus) but different for "piranhas" (Serrasalmus spp), "barba chata" (Pinirampus pirinampu) and the detritivorous Prochilodus nigricans. Fish Hg bioaccumulation is species specific; changes in feeding strategies brought by flooding seasons can change the bioaccumulation pattern without systematically affecting the overall accrual of methylmercury in tertiary consumer species. It appears that naturally occurring Hg and the high sediment load of the Rio Madeira are secondary factors in the Hg bioaccumulation pattern of fish species at the top of the food chain. PMID- 17356899 TI - Study of the combined effects of a peracetic acid-based disinfectant and surfactants contained in hospital effluents on Daphnia magna. AB - Hospital effluents cause environmental problems since they are 5-15 more toxic than urban effluents and they are not subjected to any pre-treatment before being discharged into urban sewage networks. The hypothesis used to explain this toxicity is the presence of disinfectants and detergents. This study is aimed at highlighting the ecotoxicity of a peracetic acid-based disinfectant to Daphnia magna, as well as the combined effects of this disinfectant in binary mixtures with three types of detergent. The detergents used here are: cetyltrimethylammonium bromide (CTAB, cationic), sodium dodecylsulfate (SDS, anionic) and Triton X-100 (TX, non-ionic). The toxicity of the mixtures is studied as a function of five predefined ratios. At the end of the study, we conclude that peracetic acid seems to be slightly toxic to Daphnia magna. Indeed, the efficient concentration inhibiting the mobility of 50% of the population of Daphnia at 24 h (EC50) is 116.6 mg/l. Globally, additive effects are observed for all the binary peracetic acid-detergent mixtures. However, for the peracetic acid TX mixture, its effects have antagonistic tendencies whereas the peracetic acid CTAB mixture has slight synergic tendencies. The mixture containing peracetic acid and SDS is slightly antagonistic for ratios containing more than 50% peracetic acid. PMID- 17356900 TI - Cities and calamities: learning from post-disaster response in Indonesia. AB - The article examines the post-disaster response to recent urban-centered calamities in Indonesia, extracting lessons learned and identifying specific implications for public health. Brief background information is provided on the December 2004 tsunami and earthquakes in Aceh and Nias and the May 2006 earthquake in Yogyakarta and Central Java provinces. Another brief section summarizes the post-disaster response to both events, covering relief and recovery efforts. Lessons that have been learned from the post-disaster response are summarized, including: (a) lessons that apply primarily to the relief phase; (b) lessons for rehabilitation and reconstruction; (c) do's and don'ts; (d) city specific observations. Finally, several implications for urban public health are drawn from the experiences to address health inequities in the aftermath of disasters. An initial implication is the importance of undertaking a serious assessment of health sector damages and needs shortly following the disaster. Then, there is a need to distinguish between different types of interventions and concerns during the humanitarian (relief) and recovery phases. As recovery proceeds, it is important to incorporate disaster preparation and prevention into the overall reconstruction effort. Lastly, both relief and recovery efforts must pay special attention to the needs of vulnerable groups. In conclusion, these lessons are likely to be increasingly relevant as the risk of urban-centered disasters increases. PMID- 17356901 TI - Trends in hepatitis B virus, hepatitis C virus, and human immunodeficiency virus prevalence, risk behaviors, and preventive measures among Seattle injection drug users aged 18-30 years, 1994-2004. AB - Injection drug users (IDUs) are at risk for infection with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Information on time trends in prevalence of these viruses among IDUs and in behaviors influencing their transmission can help define the status of these epidemics and of public health efforts to control them. We conducted a secondary data analysis combining cross-sectional data from IDUs aged 18-30 years enrolled in four Seattle-area studies from 1994 to 2004. Participants in all four studies were tested for antibody to HIV (anti-HIV), hepatitis B core antigen (anti-HBc), and HCV (anti-HCV), and completed behavioral risk assessments. Logistic regression was used to investigate trends in prevalence over time after controlling for sociodemographic, drug use, and sexual behavior variables. Between 1994 and 2004, anti-HBc prevalence declined from 43 to 15% (p < 0.001), anti-HCV prevalence fell from 68 to 32% (p < 0.001) and anti-HIV prevalence remained constant at 2-3%. Declines in anti-HBc and anti-HCV prevalence were observed within the individual studies, although not all these declines were statistically significant. The declines in anti-HBc and anti-HCV prevalence remained significant after control for confounding. Although we did not observe coincident declines in injection equipment sharing practices, there were increases in self-reported needle-exchange use, condom use, and hepatitis B vaccination. We conclude that there has been a substantial and sustained reduction in prevalence rates for HBV and HCV infection among young Seattle IDUs, while HIV rates have remained low and stable. PMID- 17356902 TI - Improving health and building human capital through an effective primary care system. AB - To improve population health, one must put emphasis on reducing health inequities and enhancing health protection and disease prevention, and early diagnosis and treatment of diseases by tackling the determinants of health at the downstream, midstream, and upstream levels. There is strong theoretical and empirical evidence for the association between strong national primary care systems and improved health indicators. The setting approach to promote health such as healthy schools, healthy cities also aims to address the determinants of health and build the capacity of individuals, families, and communities to create strong human and social capitals. The notion of human and social capitals begins to offer explanations why certain communities are unable to achieve better health than other communities with similar demography. In this paper, a review of studies conducted in different countries illustrate how a well-developed primary health care system would reduce all causes of mortalities, improve health status, reduce hospitalization, and be cost saving despite a disparity in socioeconomic conditions. The intervention strategy recommended in this paper is developing a model of comprehensive primary health care system by joining up different settings integrating the efforts of different parties within and outside the health sector. Different components of primary health care team would then work more closely with individuals and families and different healthy settings. This synergistic effect would help to strengthen human and social capital development. The model can then combine the efforts of upstream, midstream, and downstream approaches to improve population health and reduce health inequity. Otherwise, health would easily be jeopardized as a result of rapid urbanization. PMID- 17356903 TI - Urban as a determinant of health. AB - Cities are the predominant mode of living, and the growth in cities is related to the expansion of areas that have concentrated disadvantage. The foreseeable trend is for rising inequities across a wide range of social and health dimensions. Although qualitatively different, this trend exists in both the developed and developing worlds. Improving the health of people in slums will require new analytic frameworks. The social-determinants approach emphasizes the role of factors that operate at multiple levels, including global, national, municipal, and neighborhood levels, in shaping health. This approach suggests that improving living conditions in such arenas as housing, employment, education, equality, quality of living environment, social support, and health services is central to improving the health of urban populations. While social determinant and multilevel perspectives are not uniquely urban, they are transformed when viewed through the characteristics of cities such as size, density, diversity, and complexity. Ameliorating the immediate living conditions in the cities in which people live offers the greatest promise for reducing morbidity, mortality, and disparities in health and for improving quality of life and well being. PMID- 17356904 TI - Effects of integrated trauma treatment on outcomes in a racially/ethnically diverse sample of women in urban community-based substance abuse treatment. AB - This study presents findings from a quasiexperimental, nonequivalent, group design study with repeated measures that explored the effects of integrated trauma-informed services on the severity of substance abuse, mental health, posttraumatic stress disorder (PTSD) symptomatology among women with histories of trauma in urban, community-based substance abuse treatment. The study also explored if the model of integrated services was equally beneficial for women of various racial/ethnic groups. Participants in the study were 342 women receiving substance abuse treatment in intervention and comparison sites. Results indicated that at 6 and 12 month follow-ups, those in the trauma-informed intervention group, in contrast to the comparison group, had significantly better outcomes in drug abstinence rates in the past 30 days as well as in mental health and PTSD symptomatology. Results also showed that, overall, integrated services were beneficial for women across the different racial/ethnic groups in substance abuse treatment, although some differences appear to exist across racial/ethnic groups in improving addiction severity and mental health and PTSD symptomatology. PMID- 17356905 TI - Neurofeedback for children with ADHD: a comparison of SCP and Theta/Beta protocols. AB - Behavioral and cognitive improvements in children with ADHD have been consistently reported after neurofeedback-treatment. However, neurofeedback has not been commonly accepted as a treatment for ADHD. This study addresses previous methodological shortcomings while comparing a neurofeedback-training of Theta Beta frequencies and training of slow cortical potentials (SCPs). The study aimed at answering (a) whether patients were able to demonstrate learning of cortical self-regulation, (b) if treatment leads to an improvement in cognition and behavior and (c) if the two experimental groups differ in cognitive and behavioral outcome variables. SCP participants were trained to produce positive and negative SCP-shifts while the Theta/Beta participants were trained to suppress Theta (4-8 Hz) while increasing Beta (12-20 Hz). Participants were blind to group assignment. Assessment included potentially confounding variables. Each group was comprised of 19 children with ADHD (aged 8-13 years). The treatment procedure consisted of three phases of 10 sessions each. Both groups were able to intentionally regulate cortical activity and improved in attention and IQ. Parents and teachers reported significant behavioral and cognitive improvements. Clinical effects for both groups remained stable six months after treatment. Groups did not differ in behavioural or cognitive outcome. PMID- 17356906 TI - Nonfunctioning pituitary adenoma: incidence, causes of death and quality of life in relation to pituitary function. AB - The incidence of clinically significant, nonfunctioning pituitary adenoma, requiring surgical treatment, has not been established. According to previous studies, both surgery type and subsequent radiotherapy may have an impact on quality of life (QOL), and some studies have shown increased cardiovascular mortality in patients with pituitary disease. We studied all patients with functionless, suprasellar pituitary adenoma who were operated on during the period 1985-1996 (N = 192; transsphenoidal surgery = 160, craniotomy = 32). QOL was evaluated from Short Form 36 and Major Depression Inventory questionnaires. Causes of death were obtained from the Danish Register of Causes of Death. Incidence was 5.6/mill/year. Postoperatively, 27% of the patients had normal pituitary function and 27% were panhypopituitary. Fifty three patients had died. Death from cardiovascular, cerebrovascular and malignant diseases was not increased. Overall, QOL was not different from QOL of an age- and sex matched background population. QOL was, however, impaired in patients who had undergone craniotomy as compared to patients undergoing transsphenoidal surgery. QOL was not reduced in hypopituitary patients or in patients receiving radiotherapy. PMID- 17356907 TI - Molecular analysis of six segments of tobacco leaf enation virus, a novel phytoreovirus from tobacco. AB - Tobacco leaf enation virus (TLEV) is a putative member of the genus Phytoreovirus within the family Reoviridae. Previous western blot analysis of structural viral proteins (apparent molecular weights of 93 kDa; 58 kDa; 48 kDa; 39 kDa and 36 kDa) associated with TLEV, isolated from infected tobacco in South Africa, suggested that these proteins may correspond to structural Wound tumor virus (WTV) proteins. To further establish the nature of this novel virus disease phenotype in tobacco, molecular characterization of six dsRNA components was undertaken. Full-length cDNA clones were obtained by an optimized modified single primer amplification sequence-independent dsRNA cloning method. Results of this study revealed the conserved terminal sequence: 5'GG(U/C)...UGAU 3' of segments S6-S12, while adjacent to these conserved terminal sequences are imperfect inverted repeats (7-15 bp in length), both features being common to reoviruses. The complete nucleotide sequences of segments S5 (2,610 bp), S7 (1,740 bp), S8 (1,439 bp), S10 (1,252 bp), S11 (1,187 bp) and S12 (836 bp) were determined. Comparison of full-length nucleotide sequences with corresponding segments of other phytoreoviruses, Rice gall dwarf virus (RGDV), Rice dwarf virus (RDV) and WTV has shown nucleotide and predicted amino acid identities within the range of 30-60%. TLEV consistently shows a higher identity to WTV than to other phytoreovirus species where sequence data is available. Each segment had a single predicted open reading frame encoding proteins with calculated molecular weights of S5 (90.6 kDa); S7 (58.1 kDa); S8 (47.7 kDa); S10 (39.8 kDa); S11 (35 kDa) and S12 (19.5 kDa). The relatively low nucleotide and amino acid identity to other members of the genus demonstrates that TLEV is a novel phytoreovirus, distinct from the only other reported dicotyledenous-infecting WTV and is the first phytoreovirus reported to emerge in Africa. PMID- 17356908 TI - The ryegrass mottle virus genome codes for a sobemovirus 3C-like serine protease and RNA-dependent RNA polymerase translated via -1 ribosomal frameshifting. AB - In the course of sobemovirus gene cloning the complete genome of Ryegrass mottle virus (RGMoV) was sequenced. Sequence analysis revealed differences including missing and extraneous nucleotides in comparison to the previously published sequence (Zhang, Toriyama, Takanashi, J. Gen. Plant Pathol. 67, 63 (2001)). A gene coding for a typical sobemovirus 3C-like serine protease was identified in ORF2a after multiple sequence alignment analysis. The newly identified 57-amino acid stretch in ORF2a showed similarities ranging from 38.5 to 50.9% among sequenced genes of sobemovirus proteases. ORF analysis of the RGMoV polyprotein coding sequence demonstrated the arrangement of ORF2b coding for RNA-dependent RNA polymerase (RdRP) in the -1 frame in regard to ORF2a. The localization of conserved among sobemoviruses slippery sequence (UUUAAAC) at the 3'-end of ORF2a suggests the translation of RdRP via a -1 ribosomal frameshifting mechanism, allowing to include the RGMoV in the sobemovirus group with a Cocksfoot mottle virus-like (CfMV-like) genome organization. PMID- 17356909 TI - Adaptive evolution of the first extra exon in the murid rodent prolactin gene family. AB - The prolactin gene family in rodents consists of multiple members that coordinate the processes of reproduction and pregnancy. Some members of this family acquired one or two additional exons between exon 2 and exon 3 of the prototypical 5-exon, 4-intron structure, but the evolutionary importance of this insertion is unclear. Here, we focus on those members and survey this question by molecular evolutionary methods. Phylogenetic analysis shows that those members cluster into two distinct groups. Further analysis shows that the two groups of genes originated before the divergence of mouse and rat but after that of rodents from other mammals. We compared the d (N)/d (S) values for each branch of the gene tree but found no evidence to support positive selection for any branch. We found strong evidence, however, that one site (11E) of the 13 sites of the first extra exon underwent positive selection by the site-specific models of the maximum likelihood method. Combining our molecular evolutionary analysis with other known functional evidence, we believe that the insertion of the extra exon implies some functional adaptation. PMID- 17356910 TI - Anti-arrhythmic effects of I (Na), I (Kr), and combined I (Kr)-I (CaL) blockade in an experimental model of acute stretch-related atrial fibrillation. AB - INTRODUCTION: Atrial dilatation is commonly associated with atrial fibrillation (AF), but the electrophysiological mechanisms and the implications for anti arrhythmic therapy are poorly understood. In a model of acute stretch-related AF in isolated rabbit hearts, we evaluated the electrophysiological effects of three different anti-arrhythmic drugs: dofetilide, flecainide and BRL-32872 (associating I (Kr) and I (CaL) blocking properties). METHODS: After 30 min of sustained stretch-related AF, we perfused BRL 10-7 M, BRL 3.10-7 M, BRL 10-6 M, flecainide 2.4 10-6 M and dofetilide 10-7 M and iteratively measured atrial effective refractory periods (ERPs), AF inducibility and AF cycle length (AFCL) 15, 30 and 60 min after drug perfusion, respectively. RESULTS: After a significant shortening of the ERPs by acute atrial stretch in the five groups individually (p < 0.001, stretch vs baseline for each group individually), drug perfusion led to a strong lengthening of AFCL, a very significant prolongation of ERPs (p < 0.001 vs stretch) and a reduction of AF inducibility (p < 0.01 vs control group) for each of the five experimental groups. The relative ERP increase was comparable in all groups, whereas a significantly lower AF inducibility was observed in the BRL 10-6 M group (p < 0.05 vs other BRL concentrations). CONCLUSION: In a model of acute stretch-related AF, dofetilide, flecainide and BRL-32872 terminated AF and prevented its immediate reinduction after having comparatively prolonged AFCL and ERPs. These comparative results suggest that those drugs are equally efficacious, albeit with different mechanisms, in the setting of acute atrial stretch. PMID- 17356911 TI - Low endometrial volume may predict early pregnancy loss in women undergoing in vitro fertilization. AB - PURPOSE: To evaluate the role of 3-D US measurement of the endometrium during early IVF-pregnancy and before the appearance of gestational sac in the prediction of pregnancies outcome. METHODS: 60 pregnant women following IVF treatment were included in the study. The women underwent transvaginal 3D US measurements of endometrial volume and thickness on day 15-17 post ET. Patients were followed and classified according to pregnancy outcome into 2 further groups. The group with early pregnancy loss and the group with ongoing pregnancy. RESULTS: While no differences were observed between those who miscarried and those who did not in gestational age, endometrial thickness or volume, spontaneous early pregnancy loss was significantly higher in patients with endometrial volume <2 mL as compared to those with endometrial volume >2 mL. CONCLUSIONS: 3-D US measurement of endometrial volume of less than 2 mL during early IVF pregnancy and prior to the appearance of gestational sac is a powerful predictor of pregnancy loss. PMID- 17356912 TI - Structure determination of a sulfated N-glycans, candidate for a precursor of the selectin ligand in bovine lung. AB - To clarify the structure of non-sialic acid anionic residue on N-glycans in the mammalian tissues, we have isolated sialidase-resistant anionic residue on N glycans from bovine lung. Analyses by partial acid hydrolysis and glycosidase digestions combined with a two-dimensional HPLC mapping method revealed that the major sialidase-resistant anionic N-glycan had a fucosylbianntenary core structure. The anionic residue was identified as a sulfate ester by methanolysis, anion-exchange chromatography, and mass spectrometry. The linkage position of the sulfate ester was the 6-position of the GlcNAc residue on the Manalpha1-6 branch. This conclusion was based on the results of glycosidase digestions followed by two-dimensional HPLC mapping. Furthermore, the disialylated form of this sulfated glycan was dominant, and no asialo form was detected. The structure of the major anionic N-glycan prepared from bovine lung and having a sulfate was proposed to be the pyridylamino derivative of Siaalpha2-3Galphalbeta1-4(HSO(3)-6)GlcNAcbeta1 2Manalpha1-6(Siaalpha2-3Galbeta1-4GlcNAcbeta1-2Manalpha1-3)Manbeta1-4GlcNAcbeta1 4(Fucalpha1-6)GlcNAc. PMID- 17356913 TI - Diagnostic yield and impact of capsule endoscopy on management of patients with gastrointestinal bleeding of obscure origin. AB - This study assessed diagnostic yield and impact of capsule endoscopy on patient management. Seventy-five patients with obscure gastrointestinal bleeding were included. Clinical and followup information was collected by review of patient records and with personal contact with the referring physicians. All previous clinical information and interventions after capsule endoscopy and clinical outcome were noted. The indication was obscure-overt gastrointestinal bleeding in 36 patients (48%) and obscure-occult gastrointestinal bleeding in 39 patients (52%). Overall diagnostic yield was 66.7% considering relevant lesions. Followup was available in 31 patients. Capsule endoscopy changed clinical management in 61.4%. Multivariate analysis showed that patients with another potential source of bleeding and patients whose onset was hematochezia were not good candidates for capsule endoscopy. Capsule endoscopy has a high diagnostic yield and a positive influence on clinical management in a high proportion of patients with obscure gastrointestinal bleeding. PMID- 17356914 TI - Methylenetetrahydrofolate reductase C677T mutation and nonalcoholic fatty liver disease. AB - A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is known as one of the causes of hyperhomocyteinemia. The oxidation products of homocysteine can initiate lipid peroxidation, which has a central role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to assess the possible role of the MTHFR C677T mutation in the progression of simple steatosis to an advanced form of NAFLD. Thirty-four patients with NAFLD diagnosed by histologic analysis and 282 healthy controls were included in the study. The discrimination of nonalcoholic steatohepatitis (NASH) from another NAFLD was made by NAFLD activity score (NAS), and a NAS>or=5 was considered NASH. Patients with either NASH or nonalcoholic fatty liver (NAFL) and controls were evaluated for frequency of the MTHFR C677T mutation. The frequency of the MTHFR C677T mutation was 53.5% (CT, 44.7%; TT, 8.9%) in controls and 41.5% (CT, 37.7%; TT, 3.8%) in patients (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.34-1.12). There was no statistical difference in the frequency of this genotype between patients with NAFL and those with NASH (36% [CT, 28%; TT, 8%] vs 46.4% [CT, 46.4; TT, 0%]; OR, 0.65; 95% CI, 0.22-1.96). According to this study, the MTHFR C677T mutation does not seem to be a risk factor for the progression of NAFL to NASH. PMID- 17356915 TI - Correlation of clinical and histopathological with endoscopic findings of celiac disease in the Turkish population. AB - Endoscopic findings have been described for the diagnosis of celiac disease but the relationship among the clinical presentation, endoscopic markers, and the degree of histopathological findings is not clear. Thirty patients who were thought to have celiac disease were included in this study. Biopsies taken from the duodenum were examined histopathologically. The relationship among the endoscopic, clinical, and histopathological findings were investigated. Partial villous atrophy was seen in 14 patients (46.6%), and subtotal and total villous atrophy were seen in 6 (20%) patients each. Eighty six percent of patients with a mosaic appearance, 76% of patients with the finding of loss of folds, and 90% of patients with scalloping on endoscopy had either partial villous atrophy, subtotal villous atrophy, or total villous atrophy on biopsy. We conclude that endoscopic findings in celiac disease can reveal valuable information both for diagnosis and for demonstration of the severity of the disease state. PMID- 17356916 TI - Ischemic preconditioning and intermittent ischemia preserve bile flow in a rat model of ischemia reperfusion injury. AB - Ischemia and reperfusion (IR) injury of the liver is associated with impaired bile secretion, but the effects of ischemic preconditioning (IPC) and intermittent ischemia (INT) on bile flow are unknown. A rat model of segmental (60%-70%) hepatic ischemia and reperfusion was employed to test the effects of IPC and INT on bile flow. Continuous clamping for 45 min (CC) substantially reduced bile flow, and this did not recover after 60 min of reperfusion. IPC and INT caused a significant recovery of bile flow. The elevation in plasma liver marker enzymes induced by CC was not reduced by IPC and INT. Light microscopy showed mild hepatocyte damage in all groups. In the CC group, the amount of F actin localized around the bile canaliculi in the ischemic lobes was less than that in the nonischemic lobes, but this difference was not observed in the IPC and INT groups. It is concluded that IPC and INT substantially alleviate the decrease in bile flow induced by ischemia. Bile flow may be useful in the assessment of IR injury. PMID- 17356917 TI - Intestinal permeability and antigliadin antibody test for monitoring adult patients with celiac disease. AB - Celiac disease causes chronic inflammation of the intestinal mucosa and reduces surface absorption; after the withdrawal of gluten from the diet, there are clinical and histologic improvements. The intestinal permeability test and serologic tests are useful for confirming the diagnosis and monitoring patients. The goal of this study is to compare the antigliadin antibody (AGA) test with the intestinal permeability test for celiac patients on a gluten-free diet. The sample consisted of 22 celiac patients who were antigliadin immunoglobulin A positive before treatment. After 12 months on a gluten-free diet, AGA testing was repeated and the intestinal permeability test was performed. A control group was composed of 11 healthy individuals. AGA remained positive in 40.9% of celiac patients, and the mean urinary lactulose excretion was 10.27%, that of mannitol was 10.18%, and the lactulose/mannitol ratio was 1.02. In the subgroup in which antigliadin became negative (59.1%), the value for lactulose was 3.79%, that for mannitol was 11.12%, the lactulose/mannitol ratio was 0.38, and the p value was less than 0.0001, 0.66, and less than 0.0001, respectively. When the two celiac subgroups were compared with the control group, the urinary lactulose excretion and the lactulose/mannitol ratio was less in the control group, whereas urinary mannitol excretion was greater. The p values were less than 0.0001 for the three variables, suggesting persistent lesions in mucosa of both subgroups, although to a lesser degree for those that became AGA negative. It is concluded that intestinal permeability allows a more precise clinical physiopathologic correlation than antigliadin and offers more information for the monitoring of these patients. PMID- 17356918 TI - Fibromyxoma of the small bowel: a review. PMID- 17356919 TI - Dimensions and circumferential stress-strain relation in the porcine esophagus in vitro determined by combined impedance planimetry and high-frequency ultrasound. AB - The mechanical properties of the esophagus are important for its function because the esophagus is subjected to changes in wall stress and strains caused by the passage of boli and the action of peristalsis. Electrodes for impedance planimetry and an ultrasound transducer were placed on the probe inside a fluid filled bag and used to study the circumferential stress and strain relation of the porcine esophagus in vitro. Impedance planimetry was used to determine the luminal cross-sectional area (CSA) and high-frequency ultrasound was used to determine the esophageal wall thickness during bag distension. Circumferential stress and strain were computed from steady-state values of pressure, CSA, and wall thickness. The incremental elastic modulus was obtained from the slope of the stress-strain curve and was plotted as a function of strain. The steady state pressure-CSA relation was nonlinear. At the lowest and highest luminal pressure load of 1 and 5 kPa, the steady state CSA was 159+/-20 and 338+/-25 mm(2), respectively. In the same pressure range, the wall thickness decreased from 1.93+/-0.08 to 1.44+/-0.08 mm. The slope of the stress-strain curve was 2.58+/ 0.35 kPa. The circumferential stress and the incremental elastic modulus as function of the strain were exponential, that is, the tissue was soft at physiologic pressures and stiffer in the supraphysiologic pressure range. These biomechanical properties of the esophageal wall seem to prevent overstretch of the esophageal wall when luminal loading becomes supraphysiologic. PMID- 17356920 TI - Activation of beta-catenin in the stem cell region of crypts during growth of the small intestine in infant rats. AB - The Wnt/beta-catenin pathway has been proposed as promoting intestinal stem cell division. Wnt ligands activate cytoplasmic beta-catenin and increase nuclear translocation of beta-catenin that binds to the Tcf-4 transcription factor. The aim of this study was to investigate beta-catenin expression in the stem cell region of crypts during intestinal growth in rats. Litters of DAxPVG/c rats were humanely killed at 7, 14, 21, 35, and 72 days of life. beta-Catenin and Tcf-4 were quantified by immunoperoxidase staining and image analysis with cumulative signal analysis. Cytoplasmic and nuclear expression of beta-catenin peaked nearly 2-fold at day 14 (versus day 7) of life in the stem cell region of intestinal crypts. Tcf-4 nuclear expression peaked earlier at 7 days and was lower thereafter with age. We conclude that the Wnt/beta-catenin pathway is activated in the stem cell region of intestinal crypts during growth of the small intestine. PMID- 17356921 TI - The sphincter of oddi. PMID- 17356922 TI - Relationship between defenses, personality, and affect during a stress task in normal adolescents. AB - OBJECTIVE: Although there are extensive data on the relationship between personality and stress reactivity in adults, there is little comparable empirical research with adolescents. This study examines the simultaneous relationships between long term functioning (personality, defenses) and observed stress reactivity (affect) in adolescents. METHODS: High school students (N = 169; mean age 16; 73 girls) were asked to participate in two conditions of the Stress Induced Speech Task (SIST): Free Association and Stressful Situation. Immature and mature defenses, distress and restraint personality dimensions, and negative and positive affect were examined. RESULTS: Greater reported use of immature defenses was significantly associated with negative affect, whereas greater reported use of mature defenses was significantly associated with greater positive affect. Although personality style was also a significant predictor of negative affect across two out of three conditions, defenses were better overall predictors of affect than were personality dimensions. Gender was also a significant predictor of negative affect, wherein girls reported more negative affect than boys. DISCUSSION: Defenses and personality style predict affective response during a moderately stressful task. Immature defenses and, to a lesser extent, the distress personality dimension predict mobilization of negative affect, whereas mature defenses predict the reporting of positive affect. These results relate to processes central to psychotherapy: defensive responding, personality style, and affective reactivity during the recounting of stressful events. PMID- 17356923 TI - Mucosal tolerance to KLH reduces BSA-induced arthritis in rats--an indication of bystander suppression. AB - Mucosal tolerance has been shown to reduce disease severity in animal models mimicking human autoimmune diseases. The objective of this study was to examine whether mucosal tolerance against keyhole limpet haemocyanin (KLH) could be used to reduce bovine serum albumin (BSA)-induced arthritis in rats and whether anti inflammatory drugs or passive cigarette smoke affected tolerance induction. Arthritis was induced by immunizing rats with BSA and then injecting BSA into one knee and saline into the other knee for comparison. Prior to BSA immunization, the rats were treated intranasally with KLH or saline and KLH then injected in the knee joints at the time of BSA injection, or the rats were treated with or without anti-inflammatory drugs or subjected to cigarette smoke prior to and during intranasal treatment with BSA. The rats that received intranasal treatment with KLH had a significantly less inflammation in their left knee joint compared to rats that received intranasal saline treatment. Beclamethasone increased the tolerance effect of BSA, whereas passive cigarette smoke abrogated the mucosal tolerance. This data suggests that bystander suppression can be used to treat arthritis and other autoimmune diseases, even when the autoantigen is not known. PMID- 17356924 TI - Gestational age shortening in single births at term. Italy 1990-1998. AB - The increasing incidence of moderate preterm births (32-36 gestation weeks) might reflect a more general tendency toward a shortening of the gestational length occurring also in the term births (37 + gestation weeks). We examined all Italian 1st live born singletons (n = 2,356,365) and found that from 1990 to 1998 the births of 40 + gestation weeks decreased from 60.7 to 51.7% and among term births the average gestation weeks decreased from 39.74 to 39.55. In term pregnancies the effect of low education and advanced age of the mother in decreasing the gestational length persisted over time, but, independently of the maternal factors, the pregnancies experienced a progressive shortening. The finding, if confirmed for other countries, should deserve further investigations on possible determinants, as improved estimates of gestational age through the widespread use of prenatal ultrasound or diffusion of hazardous and stressing working and living conditions. PMID- 17356925 TI - Reliability and validity of self-reported physical activity in the Nord-Trondelag Health Study (HUNT 2). AB - BACKGROUND: To validate the physical activity (PA) questionnaire in Nord Trondelag Health Study (HUNT 2). METHODS: The questionnaire was administered twice to a random sample of 108 men aged 20-39 and validity by comparing results with VO(2max) and ActiReg, measuring PA and energy expenditure and with the International Physical Activity Questionnaire (IPAQ). RESULTS: Spearman correlation coefficients indicated poor and moderate significant agreement by test-retest (light activity, r = 0.17, and hard activity, r = 0.50). We found a moderate significant correlation r = 0.46 (p < or = 0.01) between hard PA and VO(2max) and n.s for light activity (r = -03). Metabolic equivalent (METs) values 6+ from ActiReg most strongly correlated with hard PA r = 0.31 (p < or = 0.01), though associations of other measures obtained from ActiReg with questionnaire measures were weaker. Occupational activity was strongest correlated for METs 3-6 r = 0.48 (p < or = 0.01) by ActiReg. CONCLUSIONS: The HUNT 2 question for "hard" LTPA has acceptable repeatability and appears to be a reasonably valid measure of vigorous activity, as reflected in moderate correlations with several other measures including VO(2max), and with corresponding results from IPAQ and ActiReg. The HUNT 2 question on occupational activity had good repeatability and appears to best reflect time spent in moderate activity, with moderate associations with measured time at intermediate intensity levels. The "light" activity question from HUNT 2 had poor reproducibility and did not correlate well with most of the comparison measures. Thus, the "hard" PA and the occupational activity question should be useful measures of vigorous PA, if time and space allow only very brief assessment. The utility of the "light" PA questions remains to be established. PMID- 17356926 TI - A population-based prevalence study of hepatitis A, B and C virus using oral fluid in Flanders, Belgium. AB - Ten years after the first seroprevalence study performed in Flanders, the aim of this cross sectional study was to follow the evolution of hepatitis A, B and C prevalence. The prevalence of hepatitis A antibodies, hepatitis B surface antigen and hepatitis C antibodies was measured in oral fluid samples collected by postal survey. Using the National Population Register, an incremental sampling plan was developed to obtain a representative sampling of the general population. A total of 24,000 persons were selected and 6,000 persons among them contacted in a first wave. With 1834 participants a response rate of 30.6% was achieved. The prevalence was weighted for age and was 20.2% (95% CI 19.43-21.08) for hepatitis A, 0.66% (95% CI 0.51-0.84) for hepatitis B surface antigen and 0.12% (95% CI 0.09-0.39) for hepatitis C. The prevalence of hepatitis A and C in the Flemish population is lower in 2003 compared with the results of the study performed in 1993. The difference may be due to a real decrease of the diseases but also to differences in the methodology. The prevalence of hepatitis B surface antigen remains stable. Considering the 30% response rate and the high quality of the self-collected samples as reflect of a good participation of the general population, saliva test for prevalence study is a good epidemiological monitoring tool. PMID- 17356927 TI - Survival of patients discharged after acute myocardial infarction and evidence based drug therapy. AB - There is consensus that patients should be treated with antiplatelet agents, beta blockers, ACE-inhibitors/ARBs, and lipid lowering drugs for secondary prevention after acute myocardial infarction (AMI), but this evidence-based pharmacotherapy is underutilized. A quality improvement program was conducted in the Austrian county of Burgenland to emphasize the importance of cardiovascular drug therapy at hospital discharge in patients with AMI. In this prospective cohort study 250 members of a regional health insurance company, Burgenlandische Gebietskrankenkasse (BGKK), with AMI during the year 2003 were identified using BGKK database. Discharge prescriptions and pharmacy reimbursement data of all included patients were determined. Overall prescription rate for patients discharged from hospital after AMI (n = 207) was 86% for platelet aggregation inhibitors, 77% for ACE-inhibitors or ARBs, 72% for beta-blockers, and 68% for a lipid lowering agent including statins. The all-cause mortality rate during a mean follow-up period of 552 days was 20%. Hazard ratio (HR) for death of patients with maximum 2 medications vs. those receiving 3 or 4 medications was 2.23 (95% CI: 1.19-4.18; p = 0.012). These data demonstrate that use of evidence based drug treatment for prevention of mortality in patients with AMI is associated with risk reduction and survival benefit. Continuous quality improvement initiatives serve to improve outcome after AMI. PMID- 17356928 TI - Molecular characterization of the full-length 23S and 5S ribosomal RNA (rRNA) genes of Taylorella asinigenitalis. AB - An approximately 4.2 kbp region encoding 23S and 5S rRNA genes was identified when recombinant plasmid DNAs from two genomic DNA libraries and an inverse PCR product of Taylorella asinigenitalis UK-1 isolate were analyzed. Full-length genes of 23S rRNA (3,225 bp) and 5S rRNA (117 bp) of T. asinigenitalis are described. The present sequence analysis identified a non-coding hypothetically intrinsic transcription terminator region downstream of the 5S rRNA gene. The sequence, however, downstream of the 5S rRNA gene did not show any distal tRNA genes. Surprisingly, an intervening sequence (IVS) of 270 bp in length, including two specific tandem repeat units of 80 bp and one partial unit of 48 bp with unknown functions was identified in the first quarter of the 23S rRNA gene sequence. A second IVS of 70 bp in length was also identified in the central region of the 23S rRNA gene. In addition, by using PCR and sequencing procedures, two T. asinigenitalis isolates, UK-1 and UK-2, carried multiple IVSs in the first quarter and central regions. Moreover, the 23S rRNA fragmentation occurred in the UK-1 isolate. A phylogenetic analysis was first carried out based on the 23S rRNA sequence data from T. asinigenitalis UK-1 and 13 other beta-Proteobacteria. This is the first report of IVSs in the 23S rRNA gene from the beta-Proteobacteria. PMID- 17356929 TI - Intravitreal triamcinolone as an adjunct in the treatment of concomitant proliferative diabetic retinopathy and diffuse diabetic macular oedema. Combined IVTA and laser treatment for PDR with CSMO. AB - PURPOSE: To investigate if triamcinolone acetonide (TA) can be an adjunct to laser treatment in patients with concomitant non-high-risk proliferative diabetic retinopathy (PDR) and diffuse clinically significant diabetic macular oedema (CSMO). METHODS: This prospective, interventional and comparative clinical study included 32 eyes of 16 patients with bilateral concomitant non-high-risk PDR and diffuse CSMO. Each patient received 4 mg intravitreal TA for the eye with worse visual acuity (study group) and macular focal and grid laser photocoagulation (MP) for the other eye (control group). One month later, each patient received four sessions of panretinal photocoagulation for both eyes plus MP for the eyes in the study group. The visual and angiographic results of both groups were compared. RESULTS: In the study group, the mean visual acuity (VA) improved from 0.12 +/- 2.3 lines at the baseline to 0.19 +/- 3.1 (P = 0.004), 0.20 +/- 3.2 (P = 0.004), 0.19 +/- 3.6 (P = 0.009) and 0.19 +/- 3.3 lines (P = 0.091) at the 1-, 3 , 6- and 9-month follow-up intervals, respectively. The macular oedema was found to be resolved in 11 eyes (69%) and decreased in five eyes (31%). In the control group, the mean VA deteriorated progressively from 0.41 +/- 3.1 lines at the baseline to 0.20 +/- 3.1 lines (P = 0.026) at the end of the study and the macular oedema decreased only in three eyes (19%) at the sixth follow-up month. CONCLUSIONS: During the follow-up period of the study, intravitreal TA as an adjunct in the treatment of concomitant non-high-risk PDR and diffuse CSMO led to a more-favourable clinical outcome than conventional laser treatment. PMID- 17356930 TI - Bilateral orbital tumor formation and isolated facial palsy in Waldenstrom's macroglobulinemia. AB - A 32-year-old lady presented with bilateral painful proptosis and left infranuclear facial palsy. She was mildly anemic. Ocular examination revealed a firm non-tender mass in the super lateral quadrant of both orbits. Fine-needle aspiration cytology from the orbital mass showed the presence of lymphoplasmacytoid cells. Bone marrow aspiration also showed the presence of similar cells. An IgM monoclonal gammopathy was seen on serum protein electrophoresis. A diagnosis of Waldenstrom's macroglobulinemia was made on the basis of these findings. Hyperviscosity retinopathy is the most commonly reported ocular abnormality in Waldenstrom's macroglobulinemia. Orbital tumor formation and cranial nerve palsies are rarely reported in this condition. We describe the first case of Waldenstrom's macroglobulinemia presenting as an isolated orbital mass and facial nerve palsy. PMID- 17356931 TI - Coexisting ankylosing spondylitis and gouty arthritis. AB - The aim of this study was to investigate the clinical characteristics of patients with coexisting ankylosing spondylitis (AS) and gout. Between July 1987, and October 2004, sixty-five patients with coexisting AS and gout were enrolled. The clinical manifestations of both AS and gout in these patients were studied. Of the 65 patients included in the study, 61 were men and four were women (men-to women ratio, 15.3:1). Sixty-three subjects were Han Chinese, and two were Atayal Aborigines. Mean ages at onset of AS and gout were 29.3 +/- 15.6 years (range 7 63) and 42.2 +/- 13.2 years (range 20-74), respectively. Fifty-six patients developed gout after (15.5 +/- 11.2 years; range, 1-51 years) onset of AS; nine patients developed gout before (average, 3.4 +/- 2.2 years; range. 1-7 years) onset of AS. Forty-four (67.7%) patients had chronic peripheral arthritis and all 65 (100%) patients had acute peripheral arthritis. Thirty-three (50.8%) cases had heel pain (enthesopathy), including 22 (33.9%) with chronic heel pain, seven (10.8%) with acute heel pain, and four (6.2%) with concurrent acute and chronic heel pain. Sixty-one (93.9%) subjects were HLA-B27 antigen positive. Medical conditions potentially associated with hyperuricemia or gout were urolithiasis (n = 17), hypertension (n = 21), diabetes mellitus (n = 8), hyperlipidemia (n = 34), congestive heart failure (n = 6), coronary heart disease (n = 5), and stroke (n = 3). The following drugs were prescribed: diuretics (n = 7), low-dose aspirin (n = 4), antituberculous drugs (n = 1), and sulphasalazine (n = 34). Six (6.2%) patients had iatrogenic Cushing syndrome with adrenal insufficiency. Patients with coexisting AS and gout are not rare. Distinguishing between peripheral arthritis or enthesopathies of AS and gout is essential, especially when the course of AS arthritis becomes acute or the course of gout becomes chronic. PMID- 17356932 TI - Vertical gastrectomy for morbid obesity in 216 patients: report of two-year results. AB - BACKGROUND: The vertical gastrectomy (VG) is the restrictive part of the technically difficult biliopancreatic diversion with duodenal switch operation (DS). The VG was originally conceived of as an independent operation-the first stage of a two-stage DS that would reduce mortality and morbidity in the high risk superobese because of a shorter operating time and no anastomoses. This article presents two-year data after VG. METHODS: Laparoscopic VG was performed in a nonrandomized fashion in obese patients that met the NIH criteria for bariatric surgery. By using 5-7 firings of 45-60-mm linear 3.5-mm GI staplers along a 32-Fr bougie, a greater-curvature gastrectomy is performed and a 60-80-ml gastric tube is created. VG was compared to adjustable Lap-Band placement, Roux en-Y gastric bypass (RGB), and DS. RESULTS: Between November 2002 and August 2005, 216 patients underwent VG. The mean age was 44.7 years (range = 16-64) and 173 (80%) were female. The mean preoperative weight and body mass index (BMI) was 302 +/- 77 lbs and 49 +/- 11 kg/m2, respectively. Of the 216 patients, 5 (2.3%) had a BMI > 80 kg/m2, 6 (2.8%) had a BMI of 70-80 kg/m(2), and 25 (11.6%) had a BMI of 60-70 kg/m2. The mean operative time was 66 +/- 11 min (range = 45-180) and the mean length of hospital stay was 1.9 +/- 1.2 days. Complications occurred in 20 (6.3%) patients (vs. 7.1% after Lap-Band). Leaks occurred in 3 (1.4%) VG patients, reoperations were performed in 6 (2.8%), and no conversions to open or deaths occurred. Weight loss on par with the DS and RGB was achieved with just the VG alone. CONCLUSION: The VG operation is able to achieve significant weight loss comparable to the RGB and DS operations but with the low morbidity profile similar to that of Lap-Band placement. PMID- 17356933 TI - Cytokine response in the postoperative period after surgical treatment of benign adnexal masses: comparison between laparoscopy and laparotomy. AB - BACKGROUND: Cytokines are the main mediators of the inflammation and the response to trauma. The purpose of the present study was the comparative assessment in sera of patients with benign adnexal masses treated by laparoscopy or laparotomy of the following proinflammatory and anti-inflammatory cytokines: interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and IL-10 in the early postoperative period. METHODS: A total of 40 patients with benign adnexal masses were studied; 25 of whom underwent laparoscopy and 15, laparotomy. Blood serum concentration of IL-1beta, IL-6, IL-8, TNF-alpha, and IL-10 were measured by commercially available ELISA assays before and 4 h, 24 h, and 48 h after the operation. RESULTS: Concentrations of IL-6 were significantly increased in both groups at 4 h, 24 h, and 48 h after the surgery; levels of IL-10 showed a significant increase 4 h and 24 h after the operation; an increase in IL-1beta levels was observed only after laparotomy; no significant variations were observed in serum levels of IL-8; the postoperative increase of IL-1beta, IL-6, and IL-10 levels was more pronounced in patients undergoing laparotomy than in those treated laparoscopically; length of the surgical procedure, amount of CO2 used, tumor diameter, age, and body mass index (BMI) of the patients did not influence the postoperative patterns of the studied cytokines. CONCLUSIONS: Systemic cytokine response after operations for benign adnexal masses depends on the degree of the surgical trauma, and is less pronounced in patients undergoing laparoscopy. PMID- 17356934 TI - Management of acute malignant large-bowel obstruction with self-expanding metal stent. AB - BACKGROUND: Colorectal stents are being used for palliation and as a "bridge to surgery" in obstructing colorectal carcinoma. The purpose of this study was to review our experience with self-expanding metal stents (SEMS) as the initial interventional approach in the management of acute malignant large bowel obstruction. METHODS: Between February 2002 and May 2006, 67 patients underwent the insertion of a SEMS for an obstructing malignant lesion of the left-sided colon or rectum. RESULTS: In 55 patients, the stents were placed for palliation, whereas in 12 they were placed as a bridge to surgery. Stent placement was technically successful in 92.5% (n = 62), with a clinical success rate of 88% (n = 59). Two perforations that occurred during stent placement we retreated by an emergency Hartmann operation. In intention-to-treat by stent, the peri interventional mortality was 6% (4/67). Stent migration was reported in 3 cases (5%), and stent obstruction occurred in 8 cases (13.5%). Of the nine patients with stents successfully placed as a bridge to surgery, all underwent elective single-stage operations with no death or anastomotic complication. CONCLUSIONS: Stent insertion provided an effective outcome in patients with malignant colonic obstruction as a palliative and preoperative therapy. PMID- 17356935 TI - Laparoscopy-assisted hepatic lobectomy using hilar Glissonean pedicle transection. AB - Although many reports have described laparoscopic minor liver resections, major hepatic resection, including right or left lobectomy, has not been widely developed because of technical difficulties. This article describes a new technique for performing laparoscopy-assisted right or left hepatic lobectomy using hilar Glissonean pedicle transection. Laparoscopic mobilization of the right or left hepatic lobe is performed, including dissection of the round, faliciform, triangular, and coronary ligaments. The right or left Glissonean pedicle is encircled and divided laparoscopically. A parenchymal dissection is then performed though the upper median or right subcostal incision, through which the resected liver is removed. We successfully performed this procedure in 6 patients without blood transfusion or serious complications. Laparoscopy-assisted hepatic lobectomy using hilar Glissonean pedicle transection can be feasible and safe in highly selected patients. PMID- 17356936 TI - Thoracoscopic tracheoaortopexia for the treatment of life-threatening events in tracheomalacia. AB - BACKGROUND: Life-threatening events resulting from tracheomalacia are a well known complication of infants with esophageal atresia. Aortopexy is accepted as the most effective method for managing severe life-threatening and localized tracheomalacia with a success rate of 85% to 90%. Since the advent of minimally invasive surgery (MIS), the procedure also can be performed using thoracoscopic MIS. METHODS: Between January 2002 and November 2005, six children with esophageal atresia were treated using MIS for life-threatening events attributable to tracheomalacia. RESULTS: The patients tolerated the thoracoscopic procedure well, and all tracheoaortopexies could be performed thoracoscopically. There were two recurrences, which could be treated using thoracoscopy. After a follow-up period of 27 months (range, 10-45 months), all the patients are doing well and have had no more life-threatening events. CONCLUSIONS: Although this is the largest thoracoscopic series to date, the series is too small for any conclusions yet to be drawn. Thoracoscopic tracheoaortopexia is feasible and offers the advantages of MIS. PMID- 17356937 TI - A newly designed ergonomic body support for surgeons. AB - BACKGROUND: One of the main ergonomic problems during surgical procedures is the surgeon's awkward body posture, often accompanied by repetitive movements of the upper extremities, increased muscle activity, and prolonged static head and back postures. In addition, surgeons perform surgery so concentrated that they tend to neglect their posture. These observations suggest the advantage of supporting the surgeon's body during surgical procedures. This study aimed to design a body support and to test its potential. METHODS: The optimum working condition for a surgeon is a compromise between the spine and arm positions and the level of effort and fatigue experienced performing a procedure. The design vision of the Medisign group has led to the development of an ergonomic body support for surgeons that is suitable for use during both open and minimally invasive procedures. The feasibility of the newly designed ergonomic body support was assessed during seven surgical procedures. Electromyography (EMG) was performed for back and leg muscles using the body support in an experimental setting. RESULTS: Six of seven participating surgeons indicated that the body support was comfortable, safe, and simple to use. The EMG results show that supporting the body is effective in reducing muscle activity. The average reduction using chest support was 44% for the erector spinae muscle, 20% for the semitendinosus muscle, and 74% for the gastrocnemius muscle. The average muscle reduction using semistanding support was 5% for the erector spinae, 12% for the semitendinosus muscle, and for 50% for the gastrocnemius muscle. CONCLUSION: The results of this study imply that supporting the body is an effective way to reduce muscle activity, which over the long term may reduce physical problems and discomfort. Additionally, the product supports the surgeon in his natural posture during both open and minimally invasive procedures and can easily be adapted to the current layout of the operating theater. PMID- 17356938 TI - A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation. AB - BACKGROUND: Up to 94% of patients experience fibrous adhesions after abdominal surgery, and a significant number of these patients require a second operation for open or laparoscopic lysis of adhesions (LOA). The authors have previously shown that inhibition of the binding of tachykinin ligands to the neurokinin 1 receptor (NK-1R) using the neurokinin 1 receptor antagonist (NK-1RA) CJ-12,255 decreases primary adhesion formation and upregulates the peritoneal fibrinolytic system in a rat model. Whereas most studies have focused on the prevention of primary adhesions, few have addressed adhesion reformation after LOA. This study aimed to determine the effects of NK-1RA administration on adhesion reformation and peritoneal fibrinolytic activity after laparoscopic LOA. METHODS: Adhesions were induced in 31 rats using our previously described ischemic button model. The rats underwent laparoscopy 7 days later, during which adhesions were scored and lysed followed by administration of the NK-1RA or saline. Then 7 days after LOA, 23 rats were killed and adhesions were scored. Eight rats also were killed 24 h after the LOA to obtain peritoneal tissue and fluid, which were analyzed for tissue plasminogen activator (tPA) mRNA expression and peritoneal fibrinolytic activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and bioassay, respectively. RESULTS: At laparoscopy, 79% +/- 3% of the buttons formed adhesions. In the saline-administered control animals, 42% +/- 3.2% of the buttons reformed adhesions after LOA (p < 0.05), whereas in the animals that received the NK-1RA, 18.2% +/- 3.5% of the buttons reformed adhesions (p < 0.05). As compared with control animals, NK-1RA administration increased tPA mRNA levels by 38% and fibrinolytic activity sixfold (p < 0.05; 7.0 +/- 2.1 U/ml vs 1.2 +/- 0.54 U/ml). CONCLUSIONS: When administered during laparoscopic LOA, an NK-1RA significantly upregulates peritoneal fibrinolytic activity and decreases adhesion reformation. PMID- 17356939 TI - Thoracoscopic surgery in the management of pediatric malignancies: a multicentric survey of the Italian Society of Videosurgery in Infancy. AB - BACKGROUND: Few reports have elucidated the role of minimally invasive surgery (MIS) for pediatric malignancies. This study aimed to review the results of a multicenter study on the management of thoracic tumors in children using MIS. METHODS: A 5-year retrospective review of all MIS procedures for the treatment of pediatric malignancies performed in seven centers belonging to the Italian Society of Videosurgey in Infancy is reported. The data from 145 pediatric oncologic patients (80 girls and 65 boys) ages 30 days to 17 years (median, 7.2 years) were analyzed. Of the procedures performed, 87 were laparoscopies (60%), 55 were thoracoscopies (38%), and 3 were lumboscopies (2%). This study focused only on the results of the 55 thoracoscopic procedures performed for diagnostic purposes in 19 cases (34.6%) and for therapeutic purposes in 36 cases (65.4%). RESULTS: The duration of surgery was 15 to 180 min (median, 65 min). Metastasectomies were performed for various etiologies in 31 of the 55 cases. Of the 55 patients, 5 underwent resection of a mediastinal tumor, and 19 underwent a diagnostic thoracoscopy. During a mean follow-up period of 25.6 months, 2 (3.6%) of the 55 patients experienced perioperative complications. CONCLUSIONS: The role of MIS in tumor resection for children is currently limited, but may be used in individual cases when the preoperative workup shows it to be feasible. Its indication is strictly dependent on the thoracoscopic experience of the surgeon and the tumor site for preoperative imaging techniques. When the indication for thoracoscopy is correct, this approach has high therapeutic applicability (65.4% in our series). Our preliminary experience shows that careful patient selection and an appropriate level of technical skill make thoracoscopy a reasonable and safe option for the treatment of pediatric malignancies. PMID- 17356940 TI - Cyanoacrylate tissue sealant impairs tissue integration of macroporous mesh in experimental hernia repair. AB - BACKGROUND: Tissue sealants have been proposed as an alternative to permanent fixation devices in hernia repair with the aim of reducing perforation-associated complications and chronic pain. Sealants can be divided into three main categories: synthetic glues (e.g., cyanoacrylate based), biologic products (e.g., fibrin sealant), and genetically engineered polymer protein glues. The beneficial effects of fibrin sealant have been reported in both experimental and clinical hernia repair. However, data on cyanoacrylate glues for mesh sealing are limited. METHODS: In 20 Sprague-Dawley rats, two hernia defects (1.5 cm in diameter) per animal were created bilaterally in the midline of the abdominal wall. The peritoneum was spared. The lesions were left untreated for 10 days to achieve a chronic condition. Defects then were covered with TI-Mesh xl (2 x 2 cm), which was glued with Glubran-II. The time points of sacrifice were 17 days, 28 days, and 3 months. At autopsy, meshes were biomechanically tested, and histology was performed. RESULTS: Tissue integration of the meshes was impaired at all time points by impenetrable glue plaques. At application sites, the elasticity of the abdominal wall was significantly reduced because of nonresorbed, rigid glue residues. CONCLUSIONS: Mesh fixation by Glubran-II impairs tissue integration, elicits inflammation, and unfavorably alters the biomechanics of macroporous mesh and the abdominal wall. PMID- 17356941 TI - Incidence of tumoral pathology according to study using capsule endoscopy for patients with obscure gastrointestinal bleeding. AB - BACKGROUND: Capsule endoscopy has involved a significant advance in techniques for imaging of the small bowel. Its most frequent indication is for studying patients with obscure gastrointestinal bleeding (OGIB). Small bowel tumors are infrequent, representing only 1% to 3% of all malignant gastrointestinal tumors. This study aimed to assess retrospectively the occurrence and characteristics of tumoral pathology diagnosed by means of capsule endoscopy in patients with OGIB. METHODS: A retrospective review analyzed the first 320 patients submitted to capsule endoscopy because of OGIB (166 with obscure overt bleeding and 154 with obscure occult bleeding) at a single center. The patients with a tumor diagnosis were analyzed in terms of incidence, characteristics, and treatment of OGIB pathology. RESULTS: Tumor incidence was of 7.18% (23/320), with 65.2% of the cases supported with histologic confirmation (15/23). Obscure overt bleeding was the most frequent form of presentation, with the jejunum as the most frequent location (65.2%). For 16 patients, an intervention was conducted with a healing intent. Capsule endoscopy allowed the diagnosis of two cecal adenocarcinomas missed by colonoscopy. CONCLUSIONS: Small bowel tumors are not an infrequent cause of OGIB. Capsule endoscopy, even if it does not allow determination of the benign or malignant nature or the histologic type of the tumor, is a useful tool for the diagnosis and early management of these tumors. PMID- 17356942 TI - Prospective randomized study on perioperative enteral immunonutrition in laparoscopic colorectal surgery. AB - BACKGROUND: Perioperative nutrition for patients undergoing colon surgery seems to be effective in reducing catabolism and improving immunologic parameters. A relatively low-fiber and highly absorbable diet may facilitate the intestinal cleansing and loop relaxation fundamental for laparoscopic surgery with a lower dose of iso-osmotic laxative. METHODS: From 1 February 2004 to 30 July 2005, 28 patients referred to our unit with colon disease (neoplasms and diverticular disease) amenable to laparoscopic surgery were prospectively randomized into two groups of 14 patients each. For 6 days preoperatively, the patients in group 1 were given 750 ml/day of a diet enriched with arginine, omega-3 fatty acids, and ribonucleic acid (RNA) associated with low-fiber foods. They had 1 day of intestinal preparation with 3 l of iso-osmotic laxative. On postoperative day 2, they were fed orally with the same diet. The patients in group 2 preoperatively received a low-fiber diet. They had 2 days of preparation with iso-osmotic laxative (3 l/day). On postoperative day 3, oral nutrition was restored. Intraoperatively, we evaluated loop relaxation and intestinal cleanliness. Clinical trends were monitored in both groups, as well as adverse reactions to early nutrition. The nutritional (albumin, prealbumin) and immunologic (lymphocyte subpopulations, immunoglobulins) biohumoral parameters were evaluated at the first visit, on the day before surgery, on postoperative day 7, and 1 month after surgery. RESULTS: The two groups did not differ in terms of age, gender, distribution of disease, or baseline anthropometric, biohumoral, or immunologic parameters. There was a significant increase in CD4 lymphocytes on the day before surgery as compared with baseline parameters (p < 0.05) in group 1, but not in group 2. There was no statistically significant difference between the two groups in intestinal loop relaxation or cleanliness or in postoperative infectious complications. CONCLUSIONS: Perioperative immunonutrition proved to be safe and useful in increasing the perioperative immunologic cell response. It may contribute toward improving the preparation and relaxation of the intestinal loops despite the shorter intestinal preparation. PMID- 17356943 TI - Laparoscopic revision from LAP-BAND to gastric bypass. AB - BACKGROUND: While the majority of patients achieve good outcomes with the LAP BAND, there is a subset of patients who experience complications or fail to lose sufficient weight after the banding procedure. This study examines the feasibility and outcome of performing laparoscopic Roux-en-Y gastric bypass (RYGBP) as a single-step revision surgery after a failed LAP-BAND procedure. METHODS: In the past five years we have performed more than 1400 LAP-BAND procedures. We laparoscopically converted 33 (30 females) of these patients (mean age = 43.8 years) from LAP-BAND to RYGBP because of inadequate weight loss and/or complications. Key steps in the revision procedures were (1) identification and release of the band capsule; (2) careful dissection of the gastrogastric sutures; (3) creation of a small gastric pouch; and (4) Roux-en-Y anterior colic anterior gastric pouch-jejunum anastomosis. Revisions took place at a mean 28.2 months (range = 11-46; SD = 11.3) after the original gastric banding. Change in body mass index (BMI) between pre- and postrevision was evaluated with paired t tests. RESULTS: Among the 33 patients who would undergo revision surgery, the mean BMI before the LAP-BAND procedure was 45.7 kg/m2 (range = 39.9-53.0; SD = 3.4) and the mean weight was 126 kg (range = 99-155; SD = 17). The lowest BMI achieved by this group with the LAP-BAND before revision was 39.7 kg/m2 (range = 30-49.2; SD = 4.9); however, the mean BMI at the time of revision was 42.8 kg/m2 (range = 33.1-50; SD = 4.8). The mean revision operative time was 105 min (range = 85 175), and the mean hospital stay was 2.8 days (range = 1-10). Complications included one patient who underwent open reoperation and splenectomy for a bleeding spleen and one patient who required repair of an internal hernia. After conversion to RYGBP, mean BMI decreased to 33.9 kg/m2 at 6 months (p < 0.001) and 30.7 kg/m2 (range = 22-39.6; SD = 5.3) at 12 months or more of followup (average = 15.7 months; p < 0.0001). CONCLUSIONS: Laparoscopic conversion from LAP-BAND to RYGBP is safe and can be an alternative for patients who failed the LAP-BAND procedure. However, revision surgery is technically challenging and should be performed only by surgeons who have completed the learning curve for laparoscopic RYGBP. PMID- 17356944 TI - Face validation of the Simbionix LAP Mentor virtual reality training module and its applicability in the surgical curriculum. AB - BACKGROUND: The goal of our study was to determine expert and referent face validity of the LAP Mentor, the first procedural virtual reality (VR) laparoscopy trainer. METHODS: In The Netherlands 49 surgeons and surgical trainees were given a hands-on introduction to the Simbionix LAP Mentor training module. Subsequently, a standardized five-point Likert-scale questionnaire was administered. Respondents who had performed over 50 laparoscopic procedures were classified as "experts." The others constituted the "referent" group, representing nonexperts such as surgical trainees. RESULTS: Of the experts, 90.5% (n = 21) judge themselves to be average or above-average laparoscopic surgeons, while 88.5% of referents (n = 28) feel themselves to be less-than-average laparoscopic surgeons (p = 0.000). There is agreement between both groups on all items concerning the simulator's performance and application. Respondents feel strongly about the necessity for training on basic skills before operating on patients and unanimously agree on the importance of procedural training. A large number (87.8%) of respondents expect the LAP Mentor to enhance a trainee's laparoscopic capability, 83.7% expect a shorter laparoscopic learning curve, and 67.3% even predict reduced complication rates in laparoscopic cholecystectomies among novice surgeons. The preferred stage for implementing the VR training module is during the surgeon's residency, and 59.2% of respondents feel the surgical curriculum is incomplete without VR training. CONCLUSION: Both potential surgical trainees and trainers stress the need for VR training in the surgical curriculum. Both groups believe the LAP Mentor to be a realistic VR module, with a powerful potential for training and monitoring basic laparoscopic skills as well as full laparoscopic procedures. Simulator training is perceived to be both informative and entertaining, and enthusiasm among future trainers and trainees is to be expected. Further validation of the system is required to determine whether the performance results agree with these favorable expectations. PMID- 17356945 TI - Laparoscopic surgery and corticoadrenalomas. AB - BACKGROUND: Nowadays, laparoscopic adrenalectomy is the "gold standard" procedure for the treatment of benign lesions. However, the situation is not so clearcut when the issue is laparoscopic excision of malignant adrenal tumors. We present our results of laparoscopic adrenalectomy for treating malignant tumors over the past decade. METHODS: Between October 1995 and June 2004, 131 consecutive laparoscopic adrenalectomies were performed on 120 patients (11 synchronous bilateral procedures). All patients underwent a standardized investigation protocol during their workup for surgery. RESULTS: There were only two conversions to laparotomy (1.6%). Complications that occurred during the procedure were limited to six patients (5%). Postoperative 30-days mortality was nil. Postoperative complications occurred in five patients (4.7%) during the first 30 days of recovery. The median hospital stay for all patients was 2.5 days (range = 2-10 days). Twelve patients (9%) had a malignant tumor: nine corticoadrenalomas, one pleomorphic sarcoma, one metastatic deposit from a previously excised colonic cancer, and one malignant pheochromocytoma. At mean followup of 34 months, mean survival time was 42.3 months for corticoadrenalomas that had undergone laparoscopy versus 29.7 months for those who had had a laparotomy. Five of the nine patients are alive and well at a mean of 37 months following surgery. One patient developed pulmonary metastases one year postsurgery; they were responsive to mitotane. Five years later, the same patient had a reoperation for an intra-abdominal retrogastric recurrence of her tumor and continues to do well. Another patient developed pulmonary metastases 22 months following adrenalectomy. Two patients died of metastatic intra-abdominal disease 20 and 7 months postsurgery. CONCLUSION: When laparoscopic surgery is to used for cancer treatment, caution is the rule to maintain the primary objective of securing a survival rate at least as high as that for open surgery, without increased risk of recurrence. Considering the results presented within this study, it seems that the laparoscopic removal of a corticoadrenaloma should not worsen the prognosis, provided the surgeon respects the primary rules of oncologic resectional surgery. Any surgical conditions that would preclude the strict application of these criteria are contraindications to a laparoscopic procedure. PMID- 17356946 TI - Subcutaneous endoscopically assisted ligation (SEAL) of the internal ring for repair of inguinal hernias in children: report of a new technique and early results. AB - BACKGROUND: Open inguinal hernia repair with high ligation is an excellent method of repair in the pediatric population. Advantages of endoscopic repairs include the ability to evaluate the contralateral side, avoidance of access trauma to the vas deferens and gonadal vessels, and decreased operative time. We now report our experience with subcutaneous endoscopically assisted ligation (SEAL),: a novel technique that has proved to be a safe and effective in the treatment of inguinal hernia in the pediatric population. METHODS: The study is based on a retrospective review of 204 pediatric patients with 300 inguinal hernias treated with the SEAL technique from November 2001 to August 2003 at a tertiary referral center. Patient age ranged from 30 days to 16 years at the time of operation, with a mean follow-up of 235 days (median follow-up, 189 days). Statistical analysis was done with chi2 test, with the main outcome measures being intraoperative and postoperative complications including recurrence rate, suture abscesses, and postoperative hydroceles. RESULTS: There were 13 recurrences in 300 SEAL repairs, for a recurrence rate of 4.3% (95% C.I. 2.01%-6.65%), with only two recurrences in the last 100 repairs (2%). There were 10 suture abscesses or granulomas and 7 postoperative hydroceles. There was no statistically significant association between recurrence and gender, age at operation, history of prematurity, bilaterality, or kind of suture used. CONCLUSIONS: Our 4.3% (95% C.I. 2.01-6.65%) recurrence rate is comparable to prior series of laparoscopic repairs citing recurrence rates of 0%-5.7%. The majority of recurrences occurred within the first 4 months of developing this new procedure, with only two recurrences in the last 100 repairs. These pilot data suggest that SEAL is a safe and effective technique for inguinal hernia repair in the pediatric population. A prospective study is planned to compare this laparoscopic technique with open herniorrhaphy. PMID- 17356947 TI - Nissen fundoplication: three causes of failure (video). AB - BACKGROUND: Laparoscopic Nissen fundoplication (LNF) has become the most commonly performed antireflux procedure for gastroesophageal reflux disease. The rate of failure following fundoplication varies from 2% to 30%, and revision is required in many of the patients who have recurrent or new foregut symptoms. Common causes of failure include hiatal hernia, wrap disruption, slipped wrap, and misplaced wrap. METHODS: This video depicts three different causes of failure of LNF, each demonstrated while performing a redo fundoplication. The first case shows a common cause of failure, a misplaced wrap. Less common causes of failure are seen in the second and third cases: a retained foreign body and fundus herniation through the retroesophageal space. In the first two cases, following the dissection of the original wrap, the proper construction of a Nissen fundoplication is shown. RESULTS: The first patient developed recurrent reflux symptoms that can be explained by the misplaced wrap. In case two, the patient's dysphagia was a result of a retained foreign body from the initial procedure creating a fibrotic reaction and esophageal stricture. The final case shows how chronic failure can sometimes have an acute presentation. We see the patient's gastric fundus has herniated through the retroesophageal space and it has become incarcerated and volvulized, creating a closed loop obstruction and acute distention. CONCLUSIONS: The surgeon watching this video can appreciate the identification of various causes of LNF failure, the approach to dissection of the old wraps, and the important steps in the creation of a Nissen fundoplication. PMID- 17356948 TI - Bacterial growth efficiency in a tropical estuary: seasonal variability subsidized by allochthonous carbon. AB - Bacterial growth efficiency (BGE) is a key factor in understanding bacterial influence on carbon flow in aquatic ecosystems. We report intra-annual variability in BGE, and bacteria-mediated carbon flow in the tropical Mandovi and Zuari estuaries (southwest India) and the adjoining coastal waters (Arabian Sea). BGE ranged from 3% to 61% and showed clear temporal variability with significantly (ANOVA, p < 0.01) higher values in the estuaries (mean, 28 +/- 14%) than coastal waters (mean, 12 +/- 6%). The greater variability of BGE in the estuaries than coastal waters suggest some systematic response to nutrient composition and the variability of dissolved organic matter pools, as BGE was governed by bacterial secondary production (BP). Monsoonal rains and its accompanied changes brought significant variability in BGE and bacterial productivity/primary productivity (BP/PP) ratio when compared to nonmonsoon seasons in the estuaries and coastal waters. High BP/PP ratio (>1) together with high carbon flux through bacteria (>100% of primary productivity) in the estuarine and coastal waters suggests that bacterioplankton consumed dissolved organic carbon in excess of the amount produced in situ by phytoplankton of this region, which led to the mismatch between primary production of carbon and amount of carbon consumed by bacteria. Despite the two systems being subsidized by allochthonous inputs, the low BGE in the coastal waters may be attributable to the nature and time interval in the supply of allochthonous carbon. PMID- 17356950 TI - Optimization of hyperthermic intraperitoneal chemotherapy with oxaliplatin plus irinotecan at 43 degrees C after compete cytoreductive surgery: mortality and morbidity in 106 consecutive patients. AB - BACKGROUND: Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0-R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43 degrees C. METHODS: A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m2) combined with irinotecan (360 mg/m2) in 2 L/m2 of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43 degrees C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously, resulting in tritherapy. RESULTS: Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001). CONCLUSIONS: This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival. PMID- 17356949 TI - Culturable leaf-associated bacteria on tomato plants and their potential as biological control agents. AB - Culturable leaf-associated bacteria inhabiting a plant have been considered as promising biological control agent (BCA) candidates because they can survive on the plant. We investigated the relationship between bacterial groups of culturable leaf-associated bacteria on greenhouse- and field-grown tomato leaves and their antifungal activities against tomato diseases in vitro and in vivo. In addition, the isolated bacteria were analyzed for N-acyl-homoserine lactone (AHL) and indole-3-acetic acid (IAA) production, which have been reported to associate with bacterial colonization, and resistance to a tomato alkaloid (alpha tomatine). Leaf washings and subsequent leaf macerates were used to estimate the population size of epiphytic and more internal bacteria. Bacterial population sizes on leaves at the same position increased as the leaves aged under both greenhouse and field conditions. Field-grown tomatoes had significantly larger population sizes than greenhouse-grown tomatoes. Analysis of 16S rRNA gene (rDNA) sequencing using 887 culturable leaf-associated bacteria revealed a predominance of the Bacillus and Pseudomonas culturable leaf-associated bacterial groups on greenhouse- and field-grown tomatoes, respectively. Curtobacterium and Sphingomonas were frequently recovered from both locations. From the 2138 bacterial strains tested, we selected several strains having in vitro antifungal activity against three fungal pathogens of tomato: Botrytis cinerea, Fulvia fulva, and Alternaria solani. Among bacterial strains with strong in vitro antifungal activities, Bacillus and Pantoea tended to show strong antifungal activities, whereas Curtobacterium and Sphingomonas were not effective. The results indicated the differences in antifungal activity among predominant bacterial groups. Analysis of alpha-tomatine resistance revealed that most bacterial strains in the dominant groups exhibited moderate or high resistance to alpha-tomatine in growth medium. Furthermore, some Sphingomonas and Pantoea strains showed AHL and IAA production activities. Strain 125NP12 (Pantoea ananatis) showed particular alpha-tomatine resistance, and AHL and IAA production had the highest protective value (91.7) against gray mold. Thus, the differences of these physiological properties among dominant bacteria may be associated with the disease suppression ability of BCAs on tomato plants. PMID- 17356951 TI - Should surgical resection be combined with imatinib therapy for locally advanced or metastatic gastrointestinal stromal tumors? PMID- 17356952 TI - Gastrointestinal perforation due to bevacizumab in colorectal cancer. AB - Bevacizumab is the first U.S. Food and Drug Association-approved vascular endothelial growth factor-targeted agent that greatly increases progression-free and overall survival in combination with standard chemotherapy regimens in patients with metastatic colorectal cancer. Although bevacizumab is generally well tolerated, some serious adverse events have occurred in some patients in clinical trials, including arterial thromboembolism and gastrointestinal (GI) perforation. GI perforation was first observed in the pivotal phase 3 trial, in which six events occurred in bevacizumab group (1.5%), compared with no events in the control group. Since then, similar rates of GI perforation have been observed in other large trials. Typical presentation was abdominal pain associated with constipation and vomiting. Such events occurred throughout treatment and were not correlated with duration of exposure. No difference in rate of GI perforations was found in patients who did and did not have a baseline history of peptic ulcer disease, diverticulosis, and history of chronic use of nonsteroidal anti inflammatory drugs. However, the incidence of GI perforation seemed to be higher in patients with primary tumor intact, recent history of sigmoidoscopy or colonoscopy, or previous adjuvant radiotherapy, but it is necessary to confirm these preliminary findings by multivariate analyses. The mechanism responsible for causing GI perforation is not known and may be multifactorial. Bevacizumab should be permanently discontinued in patients who develop GI perforation. This article reviews the incidence, presentation, pathogenesis, risk factors, and management of GI perforation in patients with colorectal cancer who are treated with bevacizumab. PMID- 17356953 TI - Treatment and outcome of 82 patients with angiosarcoma. AB - BACKGROUND: Angiosarcomas are an uncommon type of malignancy that are generally thought to behave usually in a locally aggressive fashion; they often metastasize to distant sites. METHODS: Patients with a diagnosis of angiosarcoma treated at our institution between 1980 and 2006 were analyzed for patient demographics, tumor characteristics, multimodality treatment, and outcomes. RESULTS: A total of 82 patients were divided into those with primary and advanced disease. Overall, the median age was 65 (range, 22-91) years, and 44% of patients were women. Median size of tumors was 3.8 cm, and 76% of tumors were intermediate or high grade. Tumors were located throughout the body: 32 cutaneous, 22 deep soft tissues or organs, 10 radiation or lymphedema field, 8 bone, and 7 nonirradiated breast. Of 46 patients with primary disease, all patients underwent surgical resection, 67% received radiotherapy, and 27% received chemotherapy. Five-year disease-specific survival was 60%, and negative prognostic factors included intermediate or high grade, and tumors arising in a radiated or lymphedema field. Of 36 patients with advanced disease, 36% underwent a palliative operation, 78% received radiation, and 58% received chemotherapy. Median survival was just 7.3 months, and cutaneous tumors predicted a better prognosis compared with other sites. CONCLUSIONS: Primary angiosarcomas treated with aggressive surgical resection and the addition of radiation for close margins or worrisome pathologic features can result in long-term survival in most patients. The role of adjuvant chemotherapy is unclear. Patients with advanced disease have a poor prognosis, but there can be dramatic responses to chemotherapy in a minority of patients. PMID- 17356954 TI - Merkel cell carcinoma: assessing the effect of wide local excision, lymph node dissection, and radiotherapy on recurrence and survival in early-stage disease- results from a review of 82 consecutive cases diagnosed between 1992 and 2004. AB - BACKGROUND: Wide surgical excision, lymph node dissection, and radiotherapy have been used with varying efficacy in the management of early-stage Merkel cell carcinoma. METHODS: Records of 82 patients with early-stage Merkel cell carcinoma between 1992 and 2004 were reviewed. RESULTS: Forty-two patients developed a recurrence, and 44 died during the study period. Twenty-nine patients presented with regional lymph node disease, which was independently associated with diminished survival (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.55 10.75; P = .005). Lymphadenectomy was independently associated with prolonged disease-free survival (median, 28.5 vs. 11.8 months; HR, .46; 95% CI, .22-.94; P = .034) but not overall survival (P = .25). Margin-negative excision of the primary tumor (60 of 73) was not significantly associated with either prolonged disease-free survival (median, 16 vs. 14 months) or overall survival (median, 54 vs. 34 months). Forty-eight patients received radiotherapy: 36 to the primary site and 31 to the regional lymph nodes. Radiotherapy to both sites was associated with a longer median time to first recurrence (primary site, 24.2 vs. 11.8 months; regional lymph nodes, 46.2 vs. 11.3 months) and survival (primary site, 53.9 vs. 45.7 months; regional lymph nodes, 103.1 vs. 34.2 months). Administration of any radiotherapy was significantly associated with a prolonged time to first recurrence (HR, .39; 95% CI, .20-.75; P = .004) and survival (HR, .39; 95% CI, .18-.82; P = .013) on the Cox regression multivariate analyses. CONCLUSIONS: Adjuvant radiotherapy to the primary site after surgical excision is recommended in early-stage disease. Involved regional lymph nodes should be treated with radiotherapy with or without lymphadenectomy. PMID- 17356955 TI - Association of the presence of bone marrow micrometastases with the sentinel lymph node status in 410 early stage breast cancer patients: results of the Swiss Multicenter Study. AB - BACKGROUND: The sentinel lymph node (SLN) status has proven to accurately reflect the remaining axillary lymph nodes and represents the most important prognostic factor. It is unknown whether an association exists between the SLN status and the presence of bone marrow (BM) micrometastases. The objective of the present investigation was to evaluate whether or not such an association exists. METHODS: In the present investigation 410 patients with early stage breast cancer (pT1 and pT2 or =90 days of oral glucocorticoids. INTERVENTION: A multifaceted program of education and reminders delivered to primary care physicians as well as mailings and automated telephone calls to patients. OUTCOME: Either undergoing a bone mineral density (BMD) testing or filling a prescription for a bone-active medication during the 10 months of follow-up. RESULTS: After the intervention, 144 (14%) patients in the intervention group and 97 (10%) patients in the control group received either a BMD test or filled a prescription for an osteoporosis medication. This represents a 4% absolute increase and a 45% relative increase (95% confidence interval 9 93%, p = 0.01) in osteoporosis management between the intervention and control groups. No differences between groups were observed in the incidence of fracture. CONCLUSION: An intervention targeting primary care physicians and their at-risk patients increased the frequency of BMD testing and/or filling prescriptions for osteoporosis medications. However, the absolute percentage of at-risk patients receiving osteoporosis management remained low. PMID- 17356970 TI - Cultural sensitivity in screening adults for a history of childhood abuse: evidence from a community sample. AB - BACKGROUND: A number of practice guidelines and recommendations call for the assessment of childhood abuse history among adult medical patients. The cultural sensitivity of screening questions, however, has not been examined. OBJECTIVE: To assess whether questions that inquire about childhood abuse history function differently for black and white patients. DESIGN: Cross-sectional telephone surveys in 1997 and 2003. SUBJECTS: Randomly sampled adults from Memphis, Tenn (1997, N = 832; 2003, N = 967). MEASUREMENTS: Physical, emotional, and sexual abuse scales of the Childhood Trauma Questionnaire-Short Form (CTQ-SF). Standardized mean difference technique for differential item functioning to assess for possible bias in CTQ-SF items. RESULTS: Controlling for total physical abuse scale scores, black respondents were significantly (P < .01) more likely than white respondents to report that they had been punished with a hard object during their childhood, but less likely to report having being hit so hard that it left marks, have been hit so hard that someone noticed, or to believe they had been physically abused. CONCLUSIONS: Inquiries that do not explicitly differentiate physical punishment from physical abuse may not be useful for black respondents because they tend to identify black respondents who report fewer clearly abusive experiences than comparable white respondents. Although untested in this study, one possible explanation is that physical discipline may be used more frequently and may play a different role among black families than among white families. These results underline the importance of attending to cultural factors in clinical history taking about childhood abuse histories. PMID- 17356971 TI - A brief educational intervention in personal finance for medical residents. AB - INTRODUCTION: Although medical educational debt continues to escalate, residents receive little guidance in financial planning. AIM: To educate interns about long term investment strategies. SETTING: University-based medicine internship program. PROGRAM DESCRIPTION: An unselected cohort of interns (n = 52; 84% of all interns) underwent a 90-minute interactive seminar on personal finance, focusing on retirement savings. Participants completed a preseminar investor literacy test to assess baseline financial knowledge. Afterward, interns rated the seminar and expressed their intention to make changes to their long-term retirement accounts. After 37 interns had attended the seminar, a survey was administered to all interns to compare actual changes to these accounts between seminar attendees and non-attendees. MEASUREMENTS AND MAIN RESULTS: Interns' average score on the investor literacy test was 40%, equal to the general population. Interns strongly agreed that the seminar was valuable (average 5.0 on 5-point Likert scale). Of the 46 respondents to the account allocation survey, interns who had already attended the seminar (n = 25) were more likely than interns who had not yet attended (n = 21) to have switched their investments from low to high-yield accounts at the university hospital (64 vs 19%, P = 0.003) and to enroll in the county hospital retirement plan (64 vs 33%, P = 0.07). CONCLUSIONS: One 90-minute seminar on personal finances leads to significant changes in allocation of tax deferred retirement savings. We calculate that these changes can lead to substantial long-term financial benefits and suggest that programs consider automatically enrolling trainees into higher yield retirement plans. PMID- 17356972 TI - Patient access to U.S. physicians who conduct internet or e-mail consults. AB - BACKGROUND: E-mail communication has the potential to improve communication between patients and doctors. OBJECTIVE: The objective of the study is to describe the access of patients to physicians who conduct e-mail consults. METHODS: We analyzed data from the National Ambulatory Medical Care Survey (NAMCS), a nationally representative cross-sectional survey of office-based physician visits, in 2001, 2002, and 2003. The main outcome measure was the percentage of visits to a provider who reported doing internet or e-mail consults. RESULTS: There was fewer than 1 in 10 outpatient visits in 2001 (9.2%) to physicians who reported doing internet or e-mail consults, and this did not increase in 2002 (5.8%) or 2003 (5.5%). Access to these physicians was greater among patients who were male, nonminority, lived in the Western United States, seen for pre-/postoperative care, seen by a primary care provider, and not seen by a nurse during their visit. Access to physicians who conducted internet or e mail consults was independent of other patient (e.g., chronic conditions), provider (e.g., office setting), and visit (e.g., medications prescribed) characteristics. CONCLUSIONS: Access to physicians who do internet or e-mail consults is generally low and did not increase between 2001 and 2003, despite growth in internet access and in other internet-related activities. PMID- 17356973 TI - Predictors of hospitalization for injection drug users seeking care for soft tissue infections. AB - BACKGROUND: Soft tissue infections (STIs) from injection drug use are a common cause of Emergency Department visits, hospitalizations, and operating room procedures, yet little is known about factors that may predict the need for these costly medical services. OBJECTIVE: To describe a cohort of injection drug users seeking Emergency Department care for STIs and to identify risk factors associated with hospitalization. We hypothesized that participants who delayed seeking care would be hospitalized more often than those who did not. DESIGN: Cohort study using in-person structured interviews and medical record review. Logistic regression assessed the association between hospital admission and delay in seeking care as well as other demographic, clinical, and psychosocial factors. PARTICIPANTS: Injection drug users who sought Emergency Department care for STIs from May 2001 to March 2002. RESULTS: Of the 136 participants, 55 (40%) were admitted to the hospital. Delay in seeking care was not associated with hospital admission. Participants admitted for their infection were significantly more likely to be living in a shelter (P = .01) and to report being hospitalized 2 or more times in the past year (P < .01). CONCLUSIONS: We identified a subpopulation of injection drug users, mostly living in shelters, who were hospitalized frequently in the past year and who were more likely to be hospitalized for their current infections compared to others. As members of this subpopulation can be easily identified and located, they may benefit from interventions to reduce the health care utilization resulting from these infections. PMID- 17356974 TI - Perceived discrimination and adherence to medical care in a racially integrated community. AB - BACKGROUND: Past research indicates that access to health care and utilization of services varies by sociodemographic characteristics, but little is known about racial differences in health care utilization within racially integrated communities. OBJECTIVE: To determine whether perceived discrimination was associated with delays in seeking medical care and adherence to medical care recommendations among African Americans and whites living in a socioeconomically homogenous and racially integrated community. DESIGN: A cross-sectional analysis from the Exploring Health Disparities in Integrated Communities Study. PARTICIPANTS: Study participants include 1,408 African-American (59.3%) and white (40.7%) adults (> or =18 years) in Baltimore, Md. MEASUREMENTS: An interviewer administered questionnaire was used to assess the associations of perceived discrimination with help-seeking behavior for and adherence to medical care. RESULTS: For both African Americans and whites, a report of 1-2 and >2 discrimination experiences in one's lifetime were associated with more medical care delays and nonadherence compared to those with no experiences after adjustment for need, enabling, and predisposing factors (odds ratio [OR] = 1.8, 2.6; OR = 2.2, 3.3, respectively; all P < .05). Results were similar for perceived discrimination occurring in the past year. CONCLUSIONS: Experiences with discrimination were associated with delays in seeking medical care and poor adherence to medical care recommendations INDEPENDENT OF NEED, ENABLING, AND PREDISPOSING FACTORS, INCLUDING MEDICAL MISTRUST; however, a prospective study is needed. Further research in this area should include exploration of other potential mechanisms for the association between perceived discrimination and health service utilization. PMID- 17356975 TI - Lower use of hospice by cancer patients who live in minority versus white areas. AB - BACKGROUND: Although hospice care can alleviate suffering at the end of life for patients with cancer, it remains underutilized, particularly by African Americans and Hispanics. OBJECTIVE: To examine whether the racial composition of the census tract where an individual resides is associated with hospice use. DESIGN: Retrospective analysis of the Surveillance, Epidemiology, and End Results Medicare file for individuals dying from breast, colorectal, lung, or prostate cancer (n = 70,669). MEASUREMENTS: Hospice use during the 12 months before death. RESULTS: Hospice was most commonly used by individuals who lived in areas with fewer African-American and Hispanic residents (47%), and was least commonly used by individuals who lived in areas with a high percentage of African-American and Hispanic residents (35%). Hispanics (odds ratio 0.51, 95% confidence interval 0.29-0.91) and African Americans (0.56, 0.44-0.71) were less likely to use hospice if they lived in a census tract with a high percentage of both African Americans and Hispanics than if they lived in a low minority tract. African Americans and whites were less likely to receive hospice care if they lived in a census tract with a high percentage of Hispanics than if they lived in a low minority area. CONCLUSIONS: Increasing hospice use may require interventions to improve the delivery of hospice care in minority communities. PMID- 17356976 TI - Redesigning the practice model for general internal medicine. A proposal for coordinated care: a policy monograph of the Society of General Internal Medicine. AB - General Internal Medicine (GIM) faces a burgeoning crisis in the United States, while patients with chronic illness confront a disintegrating health care system. Reimbursement that rewards using procedures and devices rather than thoughtful examination and management, plus onerous administrative burdens, are prompting physicians to pursue specialties other than GIM. This monograph promotes 9 principles supporting the concept of Coordinated Care--a strategy to sustain quality and enhance the attractiveness and viability of care delivered by highly trained General Internists who specialize in the longitudinal care of adult patients with acute and chronic illness. This approach supplements and extends the concept of the Advanced Medical Home set forth by the American College of Physicians. Specific components of Coordinated Care include clinical support, information management, and access and scheduling. Success of the model will require changes in the payment system that fairly reimburse physicians who provide leadership to teams that deliver high quality, coordinated care. PMID- 17356977 TI - Fundamental reform of payment for adult primary care: comprehensive payment for comprehensive care. AB - Primary care is essential to the effective and efficient functioning of health care delivery systems, yet there is an impending crisis in the field due in part to a dysfunctional payment system. We present a fundamentally new model of payment for primary care, replacing encounter-based imbursement with comprehensive payment for comprehensive care. Unlike former iterations of primary care capitation (which simply bundled inadequate fee-for-service payments), our comprehensive payment model represents new investment in adult primary care, with substantial increases in payment over current levels. The comprehensive payment is directed to practices to include support for the modern systems and teams essential to the delivery of comprehensive, coordinated care. Income to primary physicians is increased commensurate with the high level of responsibility expected. To ensure optimal allocation of resources and the rewarding of desired outcomes, the comprehensive payment is needs/risk-adjusted and performance-based. Our model establishes a new social contract with the primary care community, substantially increasing payment in return for achieving important societal health system goals, including improved accessibility, quality, safety, and efficiency. Attainment of these goals should help offset and justify the costs of the investment. Field tests of this and other new models of payment for primary care are urgently needed. PMID- 17356978 TI - Pulmonary hypertension and amyloidosis--an uncommon association: a case report and review of the literature. AB - Only a limited number of patients with amyloidosis and pulmonary hypertension have been reported in the literature. We report a 73-year-old female with AL type amyloidosis who developed respiratory insufficiency and right heart failure because of severe pulmonary hypertension. There were no signs of cardiac involvement with amyloid or findings consistent with interstitial lung disease. Previous reports of pulmonary hypertension without an apparent parenchymal lung or myocardial involvement with amyloidosis are summarized. Pulmonary hypertension due to deposition of amyloid in the pulmonary vasculature is an uncommon finding; however, it should be considered in cases of unexplained pulmonary hypertension in patients with amyloidosis. PMID- 17356979 TI - HTLV-1-associated adult T cell leukemia lymphoma presenting as granulomatous pneumocystis jiroveci pneumonia (PJP) and hypercalcemia. AB - BACKGROUND: Since the initial description of human T cell lymphotropic virus (HTLV-1), clusters of this infection have been detected globally. Unlike HIV infection, most patients infected with HTLV-1 remain asymptomatic throughout their lifetime. CASE REPORT: We report the case of a 39-year-old Afro-Caribbean man with HTLV-1 infection presenting as hypercalcemia and granulomatous pneumocystis jiroveci pneumonia. RESULTS: Interestingly, the hypercalcemia presented with normal parathyroid hormone-related protein and low 1,25 dihydroxyvitamin D levels, and the presence of pneumocystis jiroveci in the granulomas was diagnosed with transbronchial biopsy taken during bronchoscopy. HTLV-1-associated adult T cell leukemia lymphoma (ATLL) was diagnosed in this patient by bone marrow and lymph node biopsy. CONCLUSION: Increased bone resorption, likely cytokine-mediated, is the most likely mechanism of hypercalcemia in this patient. This is believed to be the first description of this type of reaction to pneumocystis jiroveci in a HTLV-1-infected ATLL patient. PMID- 17356980 TI - Comprehending coordinated comprehensive care: the devil is in the dollars. PMID- 17356981 TI - Measuring patient and clinician perspectives to evaluate change in health-related quality of life among patients with chronic obstructive pulmonary disease. AB - CONTEXT: Many treatments aim to improve patients' health-related quality of life (HRQoL), and many care guidelines suggest assessing symptoms and their impact on HRQoL. However, there is a lack of consensus regarding which HRQoL outcome measures are appropriate to assess, and how much change on those measures depict significant HRQoL improvement. OBJECTIVE: We used triangulation methods to identify and understand clinically important differences (CIDs) for the amount of change in HRQoL that reflects both health professionals and patients' values, among patients with chronic obstructive pulmonary disease (COPD). DESIGN, SETTING, AND PARTICIPANTS: We incorporated three perspectives: (1) an expert panel of physicians familiar with the measurement of HRQoL in COPD patients; (2) 610 primary care COPD outpatients who completed baseline and bimonthly follow-up HRQoL interviews over the 12-month study; and (3) the primary care physicians (PCPs; n = 43) of these outpatients who assessed their patients' disease at baseline and at subsequent PCP visits during the year long study. MEASUREMENTS: The Chronic Respiratory Disease Questionnaire (CRQ), the Medical Outcomes Study Short Form 36-item survey (SF-36, version 2.0), and global assessments of change from each of the three perspectives for all HRQoL domains. RESULTS: With few exceptions, the CRQ was able to detect small changes at levels reported by the patients (1-2 points) and their PCPs (1-5 points). These results confirm minimal important difference standards developed in 1989 by Jaeschke et al. anchored on patient-perceived changes in HRQoL. In general, the expert panel and PCP CIDs were larger than the patient CIDs. CONCLUSION: This triangulation methodology yielded improved interpretation, understanding, and insights on stakeholder perspectives of CIDs for patient-reported outcomes. PMID- 17356982 TI - Treating homeless opioid dependent patients with buprenorphine in an office-based setting. AB - CONTEXT: Although office-based opioid treatment with buprenorphine (OBOT-B) has been successfully implemented in primary care settings in the US, its use has not been reported in homeless patients. OBJECTIVE: To characterize the feasibility of OBOT-B in homeless relative to housed patients. DESIGN: A retrospective record review examining treatment failure, drug use, utilization of substance abuse treatment services, and intensity of clinical support by a nurse care manager (NCM) among homeless and housed patients in an OBOT-B program between August 2003 and October 2004. Treatment failure was defined as elopement before completing medication induction, discharge after medication induction due to ongoing drug use with concurrent nonadherence with intensified treatment, or discharge due to disruptive behavior. RESULTS: Of 44 homeless and 41 housed patients enrolled over 12 months, homeless patients were more likely to be older, nonwhite, unemployed, infected with HIV and hepatitis C, and report a psychiatric illness. Homeless patients had fewer social supports and more chronic substance abuse histories with a 3- to 6-fold greater number of years of drug use, number of detoxification attempts and percentage with a history of methadone maintenance treatment. The proportion of subjects with treatment failure for the homeless (21%) and housed (22%) did not differ (P = .94). At 12 months, both groups had similar proportions with illicit opioid use [Odds ratio (OR), 0.9 (95% CI, 0.5-1.7) P = .8], utilization of counseling (homeless, 46%; housed, 49%; P = .95), and participation in mutual-help groups (homeless, 25%; housed, 29%; P = .96). At 12 months, 36% of the homeless group was no longer homeless. During the first month of treatment, homeless patients required more clinical support from the NCM than housed patients. CONCLUSIONS: Despite homeless opioid dependent patients' social instability, greater comorbidities, and more chronic drug use, office-based opioid treatment with buprenorphine was effectively implemented in this population comparable to outcomes in housed patients with respect to treatment failure, illicit opioid use, and utilization of substance abuse treatment. PMID- 17356984 TI - Physicians and drug representatives: exploring the dynamics of the relationship. AB - BACKGROUND: Interactions between physicians and drug representatives are common, even though research shows that physicians understand the conflict of interest between marketing and patient care. Little is known about how physicians resolve this contradiction. OBJECTIVE: To determine physicians' techniques for managing cognitive inconsistencies within their relationships with drug representatives. DESIGN, SETTING, AND PARTICIPANTS: Six focus groups were conducted with 32 academic and community physicians in San Diego, Atlanta, and Chicago. MEASUREMENTS: Qualitative analysis of focus group transcripts to determine physicians' attitudes towards conflict of interest and detailing, their beliefs about the quality of information conveyed and the impact on prescribing, and their resolution of the conflict between detailers' desire to sell product and patient care. RESULTS: Physicians understood the concept of conflict of interest and applied it to relationships with detailers. However, they maintained favorable views of physician-detailer exchanges. Holding these mutually contradictory attitudes, physicians were in a position of cognitive dissonance. To resolve the dissonance, they used a variety of denials and rationalizations: They avoided thinking about the conflict of interest, they disagreed that industry relationships affected physician behavior, they denied responsibility for the problem, they enumerated techniques for remaining impartial, and they reasoned that meetings with detailers were educational and benefited patients. CONCLUSIONS: Although physicians understood the concept of conflict of interest, relationships with detailers set up psychological dynamics that influenced their reasoning. Our findings suggest that voluntary guidelines, like those proposed by most major medical societies, are inadequate. It may be that only the prohibition of physician-detailer interactions will be effective. PMID- 17356983 TI - How do distress and well-being relate to medical student empathy? A multicenter study. AB - OBJECTIVE: To determine whether lower levels of empathy among a sample of medical students in the United States are associated with personal and professional distress and to explore whether a high degree of personal well-being is associated with higher levels of empathy. DESIGN: Multi-institutional, cross sectional survey. SETTING: All medical schools in Minnesota (a private medical school, a traditional public university, and a public university with a focus in primary care). PARTICIPANTS: A total of 1,098 medical students. MEASUREMENTS: Validated instruments were used to measure empathy, distress (i.e., burnout and symptoms of depression), and well-being (high quality of life). RESULTS: Medical student empathy scores were higher than normative samples of similarly aged individuals and were similar to other medical student samples. Domains of burnout inversely correlated with empathy (depersonalization with empathy independent of gender, all P < .02, and emotional exhaustion with emotive empathy for men, P = .009). Symptoms of depression inversely correlated with empathy for women (all P < or = .01). In contrast, students' sense of personal accomplishment demonstrated a positive correlation with empathy independent of gender (all P < .001). Similarly, achieving a high quality of life in specific domains correlated with higher empathy scores (P < .05). On multivariate analysis evaluating measures of distress and well-being simultaneously, both burnout (negative correlation) and well-being (positive correlation) independently correlated with student empathy scores. CONCLUSIONS: Both distress and well-being are related to medical student empathy. Efforts to reduce student distress should be part of broader efforts to promote student well-being, which may enhance aspects of professionalism. Additional studies of student well-being and its potential influence on professionalism are needed. PMID- 17356985 TI - Physician practice patterns and variation in the delivery of preventive services. AB - BACKGROUND: Strategies to improve preventive services delivery (PSD) have yielded modest effects. A multidimensional approach that examines distinctive configurations of physician attributes, practice processes, and contextual factors may be informative in understanding delivery of this important form of care. OBJECTIVE: We identified naturally occurring configurations of physician practice characteristics (PPCs) and assessed their association with PSD, including variation within configurations. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred thirty-eight family physicians in 84 community practices and 4,046 outpatient visits. MEASUREMENTS: Physician knowledge, attitudes, use of tools and staff, and practice patterns were assessed by ethnographic and survey methods. PSD was assessed using direct observation of the visit and medical record review. Cluster analysis identified unique configurations of PPCs. A priori hypotheses of the configurations likely to perform the best on PSD were tested using a multilevel random effects model. RESULTS: Six distinct PPC configurations were identified. Although PSD significantly differed across configurations, mean differences between configurations with the lowest and highest PSD were small (i.e., 3.4, 7.7, and 10.8 points for health behavior counseling, screening, and immunizations, respectively, on a 100-point scale). Hypotheses were not confirmed. Considerable variation of PSD rates within configurations was observed. CONCLUSIONS: Similar rates of PSD can be attained through diverse physician practice configurations. Significant within-configuration variation may reflect dynamic interactions between PPCs as well as between these characteristics and the contexts in which physicians function. Striving for a single ideal configuration may be less valuable for improving PSD than understanding and leveraging existing characteristics within primary care practices. PMID- 17356986 TI - Estimating the impact of adding C-reactive protein as a criterion for lipid lowering treatment in the United States. AB - BACKGROUND: There is growing interest in using C-reactive protein (CRP) levels to help select patients for lipid lowering therapy--although this practice is not yet supported by evidence of benefit in a randomized trial. OBJECTIVE: To estimate the number of Americans potentially affected if a CRP criteria were adopted as an additional indication for lipid lowering therapy. To provide context, we also determined how well current lipid lowering guidelines are being implemented. METHODS: We analyzed nationally representative data to determine how many Americans age 35 and older meet current National Cholesterol Education Program (NCEP) treatment criteria (a combination of risk factors and their Framingham risk score). We then determined how many of the remaining individuals would meet criteria for treatment using 2 different CRP-based strategies: (1) narrow: treat individuals at intermediate risk (i.e., 2 or more risk factors and an estimated 10-20% risk of coronary artery disease over the next 10 years) with CRP > 3 mg/L and (2) broad: treat all individuals with CRP > 3 mg/L. DATA SOURCE: Analyses are based on the 2,778 individuals participating in the 1999-2002 National Health and Nutrition Examination Survey with complete data on cardiac risk factors, fasting lipid levels, CRP, and use of lipid lowering agents. MAIN MEASURES: The estimated number and proportion of American adults meeting NCEP criteria who take lipid-lowering drugs, and the additional number who would be eligible based on CRP testing. RESULTS: About 53 of the 153 million Americans aged 35 and older meet current NCEP criteria (that do not involve CRP) for lipid lowering treatment. Sixty-five percent, however, are not currently being treated, even among those at highest risk (i.e., patients with established heart disease or its risk equivalent)-62% are untreated. Adopting the narrow and broad CRP strategies would make an additional 2.1 and 25.3 million Americans eligible for treatment, respectively. The latter strategy would make over half the adults age 35 and older eligible for lipid-lowering therapy, with most of the additionally eligible (57%) coming from the lowest NCEP heart risk category (i.e., 0-1 risk factors). CONCLUSION: There is substantial underuse of lipid lowering therapy for American adults at high risk for coronary disease. Rather than adopting CRP-based strategies, which would make millions more lower risk patients eligible for treatment (and for whom treatment benefit has not yet been demonstrated in a randomized trial), we should ensure the treatment of currently defined high-risk patients for whom the benefit of therapy is established. PMID- 17356987 TI - The impact of duty hours on resident self reports of errors. AB - BACKGROUND: Resident duty hour limitations aim, in part, to reduce medical errors. Residents' perceptions of the impact of duty hours on errors are unknown. OBJECTIVE: To determine residents' self-reported contributing factors, frequency, and impact of hours worked on suboptimal care practices and medical errors. DESIGN: Cross-sectional survey. SUBJECTS: 164 Internal Medicine Residents at the University of California, San Francisco. MEASUREMENTS AND RESULTS: Residents were asked to report the frequency and contributing factors of suboptimal care practices and medical errors, and how duty hours impacted these practices and aspects of resident work-life. One hundred twenty-five residents (76%) responded. The most common suboptimal care practices were working while impaired by fatigue and forgetting to transmit information during sign-out. In multivariable models, residents who felt overwhelmed with work (p = 0.02) and who reported spending >50% of their time in nonphysician tasks (p = 0.002) were more likely to report suboptimal care practices. Residents reported work-stress (a composite of fatigue, excessive workload, distractions, stress, and inadequate time) as the most frequent contributing factor to medical errors. In multivariable models, only engaging in suboptimal practices was associated with self-report of higher risk for medical errors (p < 0.001); working more than 80 hours per week was not associated with suboptimal care or errors. CONCLUSION: Our findings suggest that administrative load and work stressors are more closely associated with resident reports of medical errors than the number of hours work. Efforts to reduce resident duty hours may also need to address the nature of residents' work to reduce errors. PMID- 17356988 TI - Mentoring at the University of Pennsylvania: results of a faculty survey. AB - BACKGROUND: Research suggests mentoring is related to career satisfaction and success. Most studies have focused on junior faculty. OBJECTIVE: To explore multiple aspects of mentoring at an academic medical center in relation to faculty rank, track, and gender. DESIGN: Cross-sectional mail survey in mid-2003. PARTICIPANTS: Faculty members, 1,432, at the University of Pennsylvania School of Medicine MEASUREMENTS: Self-administered survey developed from existing instruments and stakeholders. RESULTS: Response rate was 73% (n = 1,046). Most (92%) assistant and half (48%) of associate professors had a mentor. Assistant professors in the tenure track were most likely to have a mentor (98%). At both ranks, the faculty was given more types of advice than types of opportunities. Satisfaction with mentoring was correlated with the number of types of mentoring received (r = .48 and .53, P < .0001), job satisfaction (r = .44 and .31, P < .0001), meeting frequency (r = .53 and .61, P < .0001), and expectation of leaving the University within 5 years (Spearman r = -.19 and -.18, P < .0001), at the assistant and associate rank, respectively. Significant predictors of higher overall job satisfaction were associate rank [Odds ratio (OR) = 2.04, CI = 1.29 3.21], the 10-point mentoring satisfaction rating (OR = 1.27, CI = 1.17-1.35), and number of mentors (OR = 1.60, CI = 1.20-2.07). CONCLUSIONS: Having a mentor, or preferably, multiple mentors is strongly related to satisfaction with mentoring and overall job satisfaction. Surprisingly, few differences were related to gender. Mentoring of clinician-educators, research track faculty, and senior faculty, and the use of multiple mentors require specific attention of academic leadership and further study. PMID- 17356989 TI - Can a chronic care model collaborative reduce heart disease risk in patients with diabetes? AB - BACKGROUND: There is a need to identify effective practical interventions to decrease cardiovascular disease risk in patients with diabetes. OBJECTIVE: We examine the impact of participation in a collaborative implementing the chronic care model (CCM) on the reduction of cardiovascular disease risk in patients with diabetes. DESIGN: Controlled pre- and postintervention study. PATIENTS/PARTICIPANTS: Persons with diabetes receiving care at 13 health care organizations exposed to the CCM collaborative and controls receiving care in nonexposed sites. MEASUREMENTS AND MAIN RESULTS: Ten-year risk of cardiovascular disease; determined using a modified United Kingdom Prospective Diabetes Study risk engine score. A total number of 613 patients from CCM intervention sites and 557 patients from usual care control sites met the inclusion criteria. The baseline mean 10-year risk of cardiovascular disease was 31% for both the intervention group and the control group. Participants in both groups had improved blood pressure, lipid levels, and HbA1c levels during the observation period. Random intercept hierarchical regression models showed that the intervention group had a 2.1% (95% CI -3.7%, -0.5%) greater reduction in predicted risk for future cardiovascular events when compared to the control group. This would result in a reduced risk of one cardiovascular disease event for every 48 patients exposed to the intervention. CONCLUSIONS: Over a 1-year interval, this collaborative intervention using the CCM lowered the cardiovascular disease risk factors of patients with diabetes who were cared for in the participating organization's settings. Further work could enhance the impact of this promising multifactorial intervention on cardiovascular disease risk reduction. PMID- 17356990 TI - Medical students' use of the stages of change model in tobacco cessation counseling. AB - BACKGROUND: Many medical schools have incorporated the Stages of Change Model into their curricula with specific application to tobacco cessation. OBJECTIVE: This study examined the extent to which medical students were prepared to provide stage-based interventions to treat nicotine dependence. DESIGN: Using a quasi experimental design, medical students' counseling interactions were evaluated with a standardized patient portraying a smoker in either the precontemplation or preparation stage of change. PARTICIPANTS: Participants were 147 third-year medical students at the University of California, San Francisco. MEASUREMENTS: Checklists completed by standardized patients evaluated students' clinical performance. Surveys administered before and after the encounters assessed students' knowledge, attitudes, confidence and previous experience with treating smoking. RESULTS: Most students asked about tobacco use (89%), advised patients of the health benefits of quitting (74%), and assessed the patient's readiness to quit (76%). The students were more likely to prescribe medications and offer referrals to patients in the preparation than in the precontemplation stage of change (P < 0.001); however, many students had difficulty identifying patients ready to quit, and few encouraged patients to set a quit date or arranged follow up to assess progress. Students' tobacco-related knowledge, but not their attitudes, confidence, or previous experience predicted their clinical performance. CONCLUSIONS: The findings indicated evidence of students tailoring their counseling strategies to the patients' stage of change; however, they still could do more to assist their patients in quitting. Additional training and integration of cessation counseling into clinical rotations are needed. PMID- 17356991 TI - Gender differences in health care utilization among veterans with chronic pain. AB - BACKGROUND: Previous research reports that 48% of veterans regularly experience and express concern over pain. Outpatient service use is higher for veterans with pain than for veterans without pain. Our study objective was to identify differences in outpatient utilization between men and women veterans with chronic pain. METHODS: We identified all men and women veterans at the Durham Veterans Affairs Medical Center in fiscal year (FY) 2002 between the ages of 21 and 60 that had two visits for the same pain location at least 6 weeks apart as determined by ICD-9 coding. Men and women were age-matched at a 2:1 ratio. We then compared the number of outpatient visits between genders in FY 2003. RESULTS: We identified 406 female and 812 male veterans. The mean number of clinic visits for women was 25.2 (SD 30.2) and for men 17.6 (SD 24.1). After adjusting for multiple pain sites, psychiatric diagnoses, age, and comorbidities, women veterans had a 27% higher rate of outpatient visits than men (incidence rate ratio [RR] 1.27, 95% confidence [CI] 1.15 to 1.41). Specifically, women had higher rates of visits to primary care (RR 1.36, 95% CI 1.24 to 1.50), physical therapy (RR 1.67, 95% CI 1.20 to 2.33), and other clinics (RR 1.28, 95% CI 1.14 to 1.44), and had a higher rate of visits to address pain (RR 1.15, 95% CI 1.02 to 1.30) than men. CONCLUSIONS: This is the first study to examine gender differences in chronic pain and utilization in the veteran population. Women veterans with chronic pain may need more resources to adequately manage chronic pain conditions as well as associated comorbidities and psychiatric disease. PMID- 17356992 TI - Reactions to uncertainty and the accuracy of diagnostic mammography. AB - BACKGROUND: Reactions to uncertainty in clinical medicine can affect decision making. OBJECTIVE: To assess the extent to which radiologists' reactions to uncertainty influence diagnostic mammography interpretation. DESIGN: Cross sectional responses to a mailed survey assessed reactions to uncertainty using a well-validated instrument. Responses were linked to radiologists' diagnostic mammography interpretive performance obtained from three regional mammography registries. PARTICIPANTS: One hundred thirty-two radiologists from New Hampshire, Colorado, and Washington. MEASUREMENT: Mean scores and either standard errors or confidence intervals were used to assess physicians' reactions to uncertainty. Multivariable logistic regression models were fit via generalized estimating equations to assess the impact of uncertainty on diagnostic mammography interpretive performance while adjusting for potential confounders. RESULTS: When examining radiologists' interpretation of additional diagnostic mammograms (those after screening mammograms that detected abnormalities), a 5-point increase in the reactions to uncertainty score was associated with a 17% higher odds of having a positive mammogram given cancer was diagnosed during follow-up (sensitivity), a 6% lower odds of a negative mammogram given no cancer (specificity), a 4% lower odds (not significant) of a cancer diagnosis given a positive mammogram (positive predictive value [PPV]), and a 5% higher odds of having a positive mammogram (abnormal interpretation). CONCLUSION: Mammograms interpreted by radiologists who have more discomfort with uncertainty have higher likelihood of being recalled. PMID- 17356993 TI - Patient satisfaction with primary care office-based buprenorphine/naloxone treatment. AB - BACKGROUND: Factors associated with satisfaction among patients receiving primary care-based buprenorphine/naloxone are unknown. OBJECTIVE: To identify factors related to patient satisfaction in patients receiving primary care-based buprenorphine/naloxone that varied in counseling intensity (20 vs 45 minutes) and office visit frequency (weekly vs thrice weekly). DESIGN AND PARTICIPANTS: One hundred and forty-two opioid-dependent subjects. MEASUREMENTS: Demographics, drug treatment history, and substance use status at baseline and during treatment were collected. The primary outcome was patient satisfaction at 12 weeks. RESULTS: Patients' mean overall satisfaction score was 4.4 (out of 5). Patients were most satisfied with the medication and ancillary services and indicated strong willingness to refer a substance-abusing friend for the same treatment. Patients were least satisfied with their interactions with other opioid-dependent patients, referrals to Narcotics Anonymous, and the inconvenience of the treatment location. Female gender (beta = .17, P = .04) and non-White ethnicity/race (beta = .17, P = .04) independently predicted patient satisfaction. Patients who received briefer counseling and buprenorphine/naloxone dispensed weekly had greater satisfaction than those whose medication was dispensed thrice weekly (mean difference 4.9, 95% confidence interval 0.08 to 9.80, P = .03). CONCLUSIONS: Patients are satisfied with primary care office based buprenorphine/naloxone. Providers should consider the identified barriers to patient satisfaction. PMID- 17356994 TI - Practice inquiry: clinical uncertainty as a focus for small-group learning and practice improvement. AB - PROBLEM: Many primary care physicians in nonacademic settings lack a collegial forum for engaging the clinical uncertainties inherent in their work. PROGRAM DESCRIPTION: "Practice Inquiry" is proposed as a set of small-group, practice based learning and improvement (PBLI) methods designed to help clinicians better manage case-based clinical uncertainty. Clinicians meet regularly at their offices/clinics to present dilemma cases, share clinical experience, review evidence for blending with experience, and draw implications for practice improvement. From 2001 through 2005, Practice Inquiry was introduced to sites in the San Francisco Bay Area as a demonstration effort. Meeting rosters, case logs, a feedback survey, and meeting field notes documented implementation and provided data for a formative, qualitative evaluation. PROGRAM EVALUATION: Of the 30 sites approached, 14 held introductory meetings. As of summer 2006, 98 clinicians in 11 sites continue to hold regularly scheduled group meetings. Of the 118 patient cases presented in the seven oldest groups, clinician-patient relationship and treatment dilemmas were most common. Clinician feedback and meeting transcript data provided insights into how busy practitioners shared cases, developed trust, and learned new knowledge/skills for moving forward with patients. DISCUSSION: Ongoing clinician involvement suggests that Practice Inquiry is a feasible, acceptable, and potentially useful set of PBLI methods. Two of the Practice Inquiry's group learning tasks received comparatively less focus: integrating research evidence with clinical experience and tracking dilemma case outcomes. Future work should focus on reducing the methodological limitations of a demonstration effort and examining factors affecting clinician participation. Set aside work time for clinicians, or other equally potent incentives, will be necessary for the further elaboration of these PBLI methods aimed at managing uncertainty. PMID- 17356995 TI - Update in HIV care. PMID- 17356996 TI - Variation in estimated Medicare prescription drug plan costs and affordability for beneficiaries living in different states. AB - BACKGROUND: Medicare Part D prescription drug plans (PDPs) implemented in January 2006 are designed to improve beneficiaries' access to pharmaceuticals and use market competition to yield affordable drug costs. Variations in estimated PDP costs for beneficiaries living in different states have not previously been characterized. OBJECTIVE: To describe variations in the estimated costs of PDPs (plan premium, copays, and coinsurance) within and across states. DESIGN: To estimate PDP costs based on 4 actual patient cases that exemplify common conditions and prescription drug combinations for Medicare beneficiaries, we used the online tool provided by the Centers for Medicare and Medicaid Services. MEASUREMENTS: Principal study outcomes included (a) variation across states in the estimated annual cost of the lowest-cost PDP for each case and (b) variation in the estimated affordability of the lowest-cost PDPs across states, based on cost-of-living-adjusted median income for zero-earner households. RESULTS: For all 4 patient cases, we found substantive within-state and between-state differences in the estimated costs of Medicare PDPs incurred by beneficiaries. The estimated annual costs to beneficiaries of the lowest-cost PDPs varied across states by as much as $320 for medications in the least expensive scenario, and by as much as $13,000 for the most expensive scenario. On average across states, a beneficiary with cost-of-living-adjusted median income would expect to spend 3% 28% of annual income to pay for medications in the lowest-cost PDPs in the 4 patient cases. The affordability of the lowest-cost plans varied across states, and for 2 of the 4 cases the lowest-cost PDP estimates were negatively correlated with cost-of-living-adjusted median income. CONCLUSIONS: Substantive differences in estimated PDP costs are evident across states for patients with common Medicare conditions. Importantly, the lowest-cost plans were not proportionally affordable with respect to state-specific cost-of-living-adjusted median income. Refinement of the Medicare drug program may be needed to improve national balance in PDP affordability for beneficiaries living in different states. PMID- 17356997 TI - The United States physician workforce and international medical graduates: trends and characteristics. AB - BACKGROUND: International medical graduates (IMGs) have been a valuable resource for the United States physician workforce, and their contribution to the United States workforce is likely to increase. OBJECTIVE: To describe the historical trends and compare the characteristics of IMGs to United States medical graduates (USMGs) in the United States. DESIGN: Longitudinal analysis of the American Medical Association Physicians' Professional Data (AMA-PPD) database using the 1978-2004 files and a comparative analysis of the characteristics of a random sample of 1,000 IMGs and a random sample of 1,000 USMGs using the 2004 file. MEASUREMENTS: Historical trends and characteristics of IMGs in the United States. RESULTS: Over the last 26 years, the number of IMGs in the United States grew by 4,873 per year reaching a total of 215,576 in 2004, about 2.4 times its size in 1978. The proportion of IMGs increased 0.12% per year, from 22.2% in 1978 to 25.6% in 2004. In 2004, compared with USMGs, IMGs were older, less likely to be board certified [Odds ratio (OR), 0.68; 95% CI, 0.53 to 0.86], less likely to work in group practice (OR, 0.60; 95% CI, 0.37 to 0.98), more likely to have Internal Medicine as practice specialty (OR, 2.10; 95% CI, 1.62 to 2.71) and more likely to be residents (OR, 1.52; 95% CI, 1.07 to 2.16). CONCLUSIONS: Over the last quarter century, the IMGs provided a significant and steady supply for the United States physician workforce that continues to grow. Policymakers should consider the consequences for both the United States and source countries. PMID- 17356998 TI - Pericardial tamponade masquerading as septic shock. AB - A 53-year-old man with steroid dependent rheumatoid arthritis presented with fever and serous articular drainage. Oral antibiotics were initially prescribed. Subsequent hemodynamic instability was attributed to septic shock. Further evaluation revealed a pericardial effusion with tamponade. Pericardiocentesis of purulent fluid promptly corrected the hypotension. Proteus mirabilis was later isolated from both the infected joint and the pericardial fluid. This is the first report of combined Proteus mirabilis septic arthritis and purulent pericarditis. It documents the potential for atypical transmission of Gram negative pathogens, to the pericardium, in patients with a high likelihood of preexisting pericardial disease. In immunocompromised patients, the typical signs and symptoms of pericarditis may be absent, and the clinical presentation of pericardial tamponade may be misinterpreted as one of septic shock. This case underscores the value of a careful physical examination and proper interpretation of ancillary studies. It further illustrates the importance of initial antibiotic selection and the need for definitive treatment of septic arthritis in immunocompromised patients. PMID- 17356999 TI - Severe acute pharyngitis caused by group C streptococcus. AB - INTRODUCTION: Adult group C beta-hemolytic streptococcal pharyngitis has a prevalence of approximately 5%. It can present with a broad spectrum of severity. CASE REPORT: We report a 30-year-old woman who presented with severe Group C streptococcal pharyngitis. DISCUSSION: She presented with a 9-day history of progressive symptoms, including fever, sore throat, neck swelling, and recent onset of hoarseness. In the 9 days before the emergency room (ER) presentation, the patient had visited the ER twice complaining of a sore throat. At both visits, the physicians performed rapid antigen strep testing. Each time her test was negative and the physicians recommended symptomatic therapy. Her symptoms continued to worsen leading to her repeat presentation. At this time she had severe pharyngitis with markedly enlarged tonsils. Neck CT excluded peritonsillar abscess. Rapid strep testing was again negative, but her throat culture grew group C beta-hemolytic streptococcus. CONCLUSION: This presentation illustrates the importance of a systematic approach to evaluating patients with negative rapid strep tests and worsening pharyngitis. PMID- 17357000 TI - Deficiencies in the quality of diabetes care: comparing specialist with generalist care misses the point. AB - The quality of diabetes care delivered to patients falls below the expectations of practice guidelines and clinical trial evidence. Studies in many jurisdictions with varying health care systems have shown that recommended processes of care occur less often than they should; hence, outcomes of care are inadequate. Many studies comparing care between specialists and generalists have found that specialists are more likely to implement processes of care. However, this provides little insight into improving quality of care, as the difference between specialists and generalists in these studies is small compared to the overall deficiency in quality. Therefore, future research should instead focus on ways to implement high quality care, regardless of specialty. To date, few methodologically rigorous studies have uncovered interventions that can improve quality of care. The development of such interventions to help all physicians implement better quality care could greatly benefit people with diabetes. PMID- 17357001 TI - Toward a biopsychosocial understanding of the patient-physician relationship: an emerging dialogue. AB - Complexity theory has been used to view the patient-physician relationship as constituted by complex responsive processes of relating. It describes an emergent, psychosocial relational process through which patients and physicians continually and reciprocally influence each other's behavior and experience. As psychosocial responses are necessarily biopsychosocial responses, patients and physicians must likewise be influencing each other's psychobiology. This mutual influence may be subjectively experienced as empathy, and may be skillfully employed by the clinician to directly improve the patient's psychobiology. PMID- 17357002 TI - Confusing inequitable medicare prescription drug benefit. PMID- 17357003 TI - Is food worth fighting for? ESS's in mixed populations of Kleptoparasites and Foragers. AB - We extend the game theoretic model of kleptoparasitism discussed in Broom et al. (2004), by considering a population of foragers consisting of two groups with different behaviours--those who forage and steal from other feeders, and those who only forage. We a sume that those who do not steal have a better foraging rate than those who are also looking out for opportunities to steal. We also allow either type to resist an attack or not resist. We look for Evolutionary Stable States, of either a mixture of the two behaviours, or where the whole population has just one of these behaviours. We find nine such ESS's, dependent on the environmental parameters, although in fact only five of these are distinguishable. In general, we find that if the overall population density is low, food-stealing becomes less viable, and there is an ESS consisting of only foragers. Conversely, when there are many animals looking for, and finding, food, there is an ESS consisting of just kleptoparasites (which are also foraging). In between, an ESS will contain both pure-foragers and stealers. There is some empirical evidence of such behaviours. We find that when there is a mixture of the two types, they must both have the same resistive behaviour. We can thus have some individuals challenging for food but not resisting challenges, and others not challenging and not resisting. This shows how aggressive behaviour may be context-dependent, as seen in practice. PMID- 17357004 TI - Clinicopathological considerations on angiogenic potential in neuroblastoma Schwannian stroma - poor tumours. AB - The aim of the study was to determine microscopic angiogenic parameters of neuroblastoma (NB) Schwannian stroma-poor tumours. Furthermore the associations between vascular parameters and clinicopathological features of tumours and basic prognostic factors were analysed. Examined tissue samples from 62 NB came from 39 untreated and 23 chemotherapy pretreated tumours. The clinicopathological data comprised: patients' age, gender, survival, tumour site and stage, tumour histology and MYCN status.The morphological analysis of the angiogenic potential concentrated on examination of vascular patterns - classical type or pathological angiogenesis with mural microvascular proliferation (MVP). The quantitative study included semi-automatic assessment of vascular density (VD) in CD34 stained tumour sections. Pathologic angiogenesis with MVP, including simple and/or glomeruloid type, was encountered in 25 cases and was more frequent in differentiating histology subtype and extraadrenal tumours. VD value ranged from 56 to 385 vessels/mm2 (median 149). Higher VD was connected with younger patient's age. In untreated tumours VD was significantly higher in infants than in children over one year of age. Pathologic type angiogenesis and lower VD were found to be associated with shorter survival. Our study confirmed high vascularization of NB and revealed common occurrence of vascular pattern with MVP. Angiogenic potential in the analysed group showed diversity related to some clinicopathological tumour features. This points toward heterogeneity of NB tumours in vascular aspects, possibly affecting tumours' reactivity to antiangiogenic therapy. PMID- 17357005 TI - Lectin binding pattern in meningiomas of various histological subtypes. AB - Altered tumour cell glycosylation in relation to cellular heterogeneity in human brain tumours remains relatively unexplored. It has been reported that meningiomas express variability in glycosylation properties; however only limited meningioma subtypes have been studied with lectins histochemistry. The aim of this study was to compare the binding pattern of biotinylated lectins in seven subtypes of histologically benign intracranial meningiomas (meningothelial, transitional, fibroblastic, psammomatous, secretory, microcystic and angiomatous types). The study was performed on biopsy material of 30 cases of meningiomas with different lectins: Peanut agglutinin (PNA), Soybean agglutinin (SBA), Dolichos biflorus agglutinin (DBA), Wheat germ agglutinin (WGA), Cocanavalin A (Con A) and Ulex europaeus agglutinin 1 (UEA-1). The expression of lectin-binding glycoconjugates exhibited differences between certain subtypes of meningiomas. WGA with affinity for GlcNAc and neuraminic acid labelled the cells of all meningiomas but most intensely those of fibroblastic type. Staining with PNA, SBA and DBA, which are GalNAc specific, varied from negative to strongly positive. Enhanced PNA reactivity reflected mainly cytoarchitectural pattern of tumour growth, such as syncytial lobules, whorled formations or trabecular arrangements of meningioma cells. DBA labelled the majority of cellular nuclei. SBA showed binding to psammoma bodies, while pseudopsammoma bodies were stained with PNA, WGA, Con A, and to a lesser extent with SBA and DBA. The secretory meningiomas exhibited strong and heterogeneous lectins reactivity within pseudopsammoma bodies whereas the neoplastic cells were only occasionally stained. The selective reactivity of UEA-1 with endothelial cells of blood vessels resulted in a specific visualisation of the vascular network in all histological subtypes of meningiomas. These results documented the heterogeneous glycosylation pattern in different subtypes of meningiomas and indicate the usefulness of lectins in the evaluation of pluripotential differentiation of meningioma cells. PMID- 17357006 TI - Granular cell meningioma. A case report. AB - We describe a granular cell tumour developing in clear cell meningioma of the falx. Granular and clear cells showed immunoreactivity for vimentin, epithelial membrane antigen and progesterone receptors. This is the first case documenting arachnoid origin of neoplastic granular cells in meningioma. PMID- 17357007 TI - Spinal accessory nerve meningioma in a paediatric patient: case report. AB - Accessory nerve meningiomas are exceedingly rare. We present a case of a nine year-old patient with neurofibromatosis type 2 who had radiologic evidence of spinal cord compression from an upper cervical/foramen magnum lesion. He was asymptomatic from this lesion, but it progressed in size. The tumor was resected and histologic investigation revealed frequent tight whorls and psammoma bodies consistent with meningioma. To the authors' knowledge, this is the first reported spinal accessory nerve meningioma in a pediatric patient. PMID- 17357008 TI - Radiation-induced brachial plexus neuropathy - aetiopathogenesis, risk factors, differential diagnostics, symptoms and treatment. AB - The success of radiation oncology has led to longer patient survival. This provides a greater opportunity for radiation injuries of the peripheral nerves to develop. Brachial plexus neuropathy in cancer patients may result from either tumour recurrence or as a consequence of radiation therapy. Distinguishing between radiation injury and cancer disease recurrence as a cause of brachial plexus dysfunction may be difficult. In this article the most important principles of the differential diagnostics have been presented. Furthermore the aetiopathogenesis of brachial plexus neuropathy after radiotherapy has been discussed as well as main risk factors, symptoms of plexopathy and methods of treatment. It ought to be emphasized that complications of radiation therapy sometimes occur many years after treatment and this may create difficulties in initial diagnostics. PMID- 17357009 TI - Brachial plexus injuries after radiotherapy - analysis of 6 cases. AB - Radiation-induced brachial plexus neuropathy is caused by compression of the nerve fibres by dense and inelastic fibrous connective tissue. In this study our own experience in treatment of lesions of the brachial plexus after radiotherapy is presented. The clinical material consisted of 6 patients aged from 40 to 64 years with injuries of the brachial plexus after radiotherapy. The analysis of the material comprised: basic disease, duration of radiotherapy, radiated fields, total dose of radiation, onset and character of symptoms, location and severity of injury. 5 women were qualified for surgical treatment. After neurolysis of the brachial plexus a significant improvement was obtained in 2 cases. In one patient remission of pain and sensory recovery was temporary. No improvement was observed in the remaining 2 patients. Lesions of the brachial plexus after radiotherapy are rare but difficult to prevent. The treatment depends on the grade of severity of injury. Surgical neurolysis is advised for grades 3 and 4 on the LENT-SOMA scale. PMID- 17357010 TI - Idiopathic hypertrophic pachymeningitis - case report and literature review. AB - Idiopathic hypertrophic pachymeningitis (IHPM) is a rare pathological state, with still unclear aetiopathogenesis. We present a case of a 63-year-old woman with cranial variety of that disease. The manifestations of the disease included headaches, paresis of VI, IX, X nerves and cerebellar ataxia. The disease was diagnosed with magnetic resonance imaging (MRI) and histopathological assessment of the pachymeninx biopsy specimen. The MRI revealed significant thickening of the cranial base pachymeninx, compressing the pons and medulla oblongata. MRI examinations could be misinterpreted as extensive meningioma of the skull base. Dura mater biopsy revealed however inflammation with abundant lymphocytic infiltrations. Clinical improvement was obtained after the application of corticosteroids. We noted the subsidence of all symptoms of the disease, as well as radiological improvement, manifested through substantial regression of the described changes in the pachymeninx. The patient has been presented in the context of 65 cases of idiopathic hypertrophic pachymeningitis, described in the literature of English-speaking countries in the last five years. Recently, the importance of the autoimmunogenic background of IHPM has been underlined. In that respect IHPM has become an interdisciplinary problem. Its diagnosis and treatment requires not only radiologists, neurologists, pathomorphologists and neurosurgeons, but also specialists in internal medicine, including immunologists, allergologists and rheumatologists as well - in other words, physicians that rarely take part in the processes of diagnosing and treating intracranial pathologies. PMID- 17357011 TI - Simultaneous lateral and posterior ponticles resulting in the formation of a vertebral artery tunnel of the atlas: case report and review of the literature. AB - The foramen arcuale is infrequently found and is potentially a clinically/surgically significant anatomical variation of the atlas. When present, the vertebral artery travels through this bony ring after exiting the transverse foramen of the atlas and prior to entering the cranium. We present a case of an adult female skeleton noted to harbor both a foramen arcuale and a lateral ponticle that resulted in the formation of a canal for the vertebral artery. The literature regarding these osteological structures is reviewed regarding their presence and potential clinical significance. The simultaneous occurrence of fully developed lateral and posterior ponticuli resulting in encasement of the third part (atlantal segment) of the vertebral artery appears to be very rare. Based on the literature regarding only foramina arcuale and their presence predisposing one to symptomatic entrapment, additional compression, as seen in our specimen, of the vertebral artery by a lateral ponticle could very likely result in stenosis of the vertebral artery. PMID- 17357012 TI - Synopsis of the CASIROZ case study: carbon sink strength of Fagus sylvatica L. in a changing environment--experimental risk assessment of mitigation by chronic ozone impact. AB - Databases are needed for the ozone (O(3)) risk assessment on adult forest trees under stand conditions, as mostly juvenile trees have been studied in chamber experiments. A synopsis is presented here from an integrated case study which was conducted on adult FAGUS SYLVATICA trees at a Central-European forest site. Employed was a novel free-air canopy O(3) fumigation methodology which ensured a whole-plant assessment of O(3) sensitivity of the about 30 m tall and 60 years old trees, comparing responses to an experimental 2 x ambient O(3) regime (2 x O(3), max. 150 nl O(3) l (-1)) with those to the unchanged 1 x ambient O(3) regime (1 x O(3)=control) prevailing at the site. Additional experimentation on individual branches and juvenile beech trees exposed within the forest canopy allowed for evaluating the representativeness of young-tree and branch-bag approaches relative to the O(3) sensitivity of the adult trees. The 2 x O(3) regime did not substantially weaken the carbon sink strength of the adult beech trees, given the absence of a statistically significant decline in annual stem growth; a 3 % reduction across five years was demonstrated, however, through modelling upon parameterization with the elaborated database. 2 x O(3) did induce a number of statistically significant tree responses at the cell and leaf level, although the O(3) responsiveness varied between years. Shade leaves displayed an O(3) sensitivity similar to that of sun leaves, while indirect belowground O(3) effects, apparently mediated through hormonal relationships, were reflected by stimulated fine-root and ectomycorrhizal development. Juvenile trees were not reliable surrogates of adult ones in view of O(3) risk assessment. Branch sections enclosed in (climatized) cuvettes, however, turned out to represent the O(3) sensitivity of entire tree crowns. Drought-induced stomatal closure decoupled O(3) intake from O(3) exposure, as in addition, also the "physiologically effective O(3) dose" was subject to change. No evidence emerged for a need to lower the "Critical Level for Ozone" in risk assessment of forest trees, although sensitive tree parameters did not necessarily reflect a linear relationship to O(3) stress. Exposure-based concepts tended to overestimate O(3) risk under drought, which is in support of current efforts to establish flux related concepts of O(3) intake in risk assessment. PMID- 17357013 TI - Free-air exposure systems to scale up ozone research to mature trees. AB - Because seedlings and mature trees do not necessarily respond similarly to O(3) stress, it is critically important that exposure systems be developed that allow exposure of seedlings through to mature trees. Here we describe three different O(3) Free-Air Exposure Systems that have been used successfully for exposure at all growth stages. These systems of spatially uniform O(3) release have been shown to provide reliable O(3) exposure with minimal, if any, impact on the microclimate. This methodology offers a welcome alternative to chamber studies which had severe space constraints precluding stand or community-level studies and substantial chamber effects on the microclimate and, hence physiological tree performance. PMID- 17357014 TI - O3 flux-related responsiveness of photosynthesis, respiration, and stomatal conductance of adult Fagus sylvatica to experimentally enhanced free-air O3 exposure. AB - Knowledge of responses of photosynthesis, respiration, and stomatal conductance to cumulative ozone uptake (COU) is still scarce, and this is particularly the case for adult trees. The effect of ozone (O(3)) exposure on trees was examined with 60-year-old beech trees (FAGUS SYLVATICA) at a forest site of southern Germany. Trees were exposed to the ambient O(3) regime (1 x O(3)) or an experimentally elevated twice-ambient O(3) regime (2 x O(3)). The elevated 2 x O (3) regime was provided by means of a free-air O(3) canopy exposure system. The hypotheses were tested that (1) gas exchange is negatively affected by O(3) and (2) the effects of O(3) are dose-dependent and thus the sizes of differences between treatments are positively related to COU. Gas exchange (light-saturated CO(2) uptake rate A(max), stomatal conductance g (s), maximum rate of carboxylation Vc (max), ribulose-1,5-bisphosphate turnover limited rate of photosynthesis J (max), CO(2) compensation point CP, apparent quantum yield of net CO(2) uptake AQ, carboxylation efficiency CE, day- and nighttime respiration) and chlorophyll fluorescence (electron transfer rate, ETR) were measured IN SITU on attached sun and shade leaves. Measurements were made periodically throughout the growing seasons of 2003 (an exceptionally dry year) and 2004 (a year with average rainfall). In 2004 Vc(max), J(max), and CE were lower in trees receiving 2 x O(3) compared with the ambient O(3) regime (1 x O(3)). Treatment differences in Vc (max), J (max), CE were rather small in 2004 (i.e., parameter levels were lower by 10 - 30 % in 2 x O(3) than 1 x O(3)) and not significant in 2003. In 2004 COU was positively correlated with the difference between treatments in A (max), g (s), and ETR (i.e., consistent with the dose-dependence of O(3)'s deleterious effects). However, in 2003, differences in A(max), g (s), and ETR between the two O(3) regimes were smaller at the end of the dry summer 2003 (i.e., when COU was greatest). The relationship of COU with effects on gas exchange can apparently be complex and, in fact, varied between years and within the growing season. In addition, high doses of O(3) did not always have significant effects on leaf gas exchange. In view of the key findings, both hypotheses were to be rejected. PMID- 17357015 TI - Flux-based response of sucrose and starch in leaves of adult beech trees (Fagus sylvatica L.) under chronic free-air O3 fumigation. AB - Investigations on sucrose and starch contents in leaves of 60-year-old beech trees ( FAGUS SYLVATICA L.) are the focus of the present study. Five trees were exposed to a twice ambient ozone regime (2 x O(3)) with a free-air canopy exposure system throughout the seasons and five trees under the prevailing ambient ozone regime served as controls (1 x O(3)). In order to examine chronic ozone (O(3)) effects, leaf samples from the sun and shade crowns of the trees were analyzed five times throughout the growing seasons in 2003 and 2004. Sucrose concentrations of leaves collected in 2004 were consistently lower than those taken in 2003, regardless of the O(3) treatment and crown position. However, the opposite was found for starch. O(3) caused a reduction of sucrose and starch contents of sun leaves in both years. Due to the fact that O(3)-responsiveness depends on the O(3) uptake through stomata during the season, all carbohydrate data were related to the cumulative O(3) uptake (COU). Little differences were found comparing sucrose and starch contents in leaves of trees grown under ambient or elevated O (3) regimes, possibly indicating the high capacity of leaves of adult beech to cope with rising O(3) exposure. Even under 2 x O(3), leaves were still able to regulate the O(3) intake by narrowing their stomata at the cost of CO(2)-uptake and sugar synthesis. In order to clarify whole-tree response patterns carbohydrate data were compared with photosynthesis, stomatal conductance and electron transport rates. In 2004 all parameters revealed a significant common response pattern to COU that indicated a reduction for all parameters under 2 x O(3). PMID- 17357016 TI - Antioxidative defence of old growth beech (Fagus sylvatica) under double ambient O3 concentrations in a free-air exposure system. AB - In this study the influence of chronic free-air ozone exposure and of different meteorological conditions in the very dry year 2003 and the more humid year 2004 on the antioxidative system in sun and shade leaves of adult FAGUS SYLVATICA trees were investigated. Contents of ascorbate, glutathione, and alpha tocopherol, as well as chloroplast pigments were determined under ambient (1 x O(3)) and double ambient (2 x O(3)) ozone concentrations. Ozone affected the antioxidative system in June and July, causing lower ascorbate contents in the apoplastic space, a more oxidized redox state of ascorbate and glutathione and an increase in pigment contents predominantly in the shade crown. For all measured parameters significant differences between the years were observed. In 2004 the redox state of ascorbate and glutathione was in a more reduced state and leaf contents of alpha-tocopherol, pigments of the xanthophyll cycle, beta-carotene, lutein, neoxanthin, and alpha-carotene were lower compared to 2003. Contents of total glutathione and chlorophyll a + b were increased in the second year. These results indicate a strong influence of the drought conditions in 2003 on the antioxidative system of beech overruling the ozone effects. Shade leaves showed lower contents of ascorbate in both years and the redox states of ascorbate and glutathione were more oxidized compared to sun leaves. Contents of photoprotective and accessory pigments generally were enhanced and the de epoxidation state of the xanthophyll cycle was lower in the shade compared to the sun crown. Exhibiting less antioxidants shade leaves seem to be more sensitive against ozone than sun leaves. PMID- 17357017 TI - Significance of ozone exposure for inter-annual differences in primary metabolites of old-growth beech (Fagus sylvatica L.) and Norway spruce (Picea abies L.) trees in a mixed forest stand. AB - The influence of long-term free-air ozone fumigation and canopy position on leaf contents of total glutathione, its redox state, non-structural proteins (NSP), soluble amino compounds, and total soluble sugars in old-growth beech (FAGUS SYLVATICA) and spruce (PICEA ABIES) trees were determined over a period of five years. Ozone fumigation had weak effects on the analysed metabolites of both tree species and significant changes in the contents of total glutathione, NSP, and soluble sugars were observed only selectively. Beech leaves were affected by crown position to a higher extent than spruce needles and exhibited lower contents of total glutathione and NSP and total soluble sugars, but enhanced contents of oxidised glutathione and amino compounds in the shade compared to the sun crown. Contents of total soluble sugars generally were decreased in shade compared to sun needles of spruce trees. Interspecific differences between beech and spruce were more distinct in the sun compared to the shade crown. Contents of total glutathione were increased whilst contents of amino compounds and total soluble sugars were lower in spruce needles compared to beech leaves. The metabolites determined showed individual patterns in the course of the five measurement years. Contents of total glutathione and its redox state correlated with air temperature and global radiation, indicating an important role for the antioxidant at low temperatures. Correlations of glutathione with instantaneous ozone concentrations seem to be a secondary effect. Differences in proteins and/or amino compounds in the inter-annual course are assumed to be a consequence of alterations in specific N uptake rates. PMID- 17357018 TI - Effects of long-term free-air ozone fumigation on delta15N and total N in Fagus sylvatica and associated mycorrhizal fungi. AB - Patterns of nitrogen (N) isotope composition (delta(15)N) and total N contents were determined in leaves, fine roots, root-associated ectomycorrhizal fungi (ECM) of adult beech trees (FAGUS SYLVATICA), and soil material under ambient (1 x O(3)) and double ambient (2 x O(3)) atmospheric ozone concentrations over a period of two years. From fine root to leaf material delta(15)N decreased consecutively. Under enhanced ozone concentrations total N was reduced in fine roots and delta(15)N showed a decrease in roots and leaves. In the soil and in most types of mycorrhizae, delta(15)N and total N were not altered due to ozone fumigation. The number of vital ectomycorrhizal root tips increased and the mycorrhizal community structure changed in 2 x O(3). Simultaneously, the specific rate of inorganic N-uptake by the roots was reduced under the double ozone regime. From these results it is assumed that 2 x O(3) changes N-nutrition of the trees at the level of N-acquisition, as indicated by enhanced mycorrhizal root tip density, altered mycorrhizal species composition, and reduced specific N uptake rates. PMID- 17357019 TI - Tree internal signalling and defence reactions under ozone exposure in sun and shade leaves of European beech (Fagus sylvatica L.) trees. AB - The influence of free-air ozone (O(3)) fumigation on the levels of gene transcripts and compounds of defence and signalling were analysed in leaves of adult beech trees from the "Kranzberg Forest" research site in 2003 and 2004. This includes the precursor of the stress hormone ethylene, ACC (1 aminocyclopropane-1-carboxylic acid), conjugated salicylic acid, lignin content as well as of the expression level of genes connected with oxidative stress and stress signalling. At this site mature beech trees were exposed to an enhanced O(3) regime by a free-air O(3) canopy exposure system. Levels of conjugated ACC and conjugated salicylic acid in leaves were increased under O (3) fumigation whereas lignin content was only slightly enhanced. Quantitative real-time RT-PCR (qRT-PCR) was performed on transcripts of genes connected with lignin, salicylic acid, and ethylene formation, the shikimate pathway, abscisic acid biosynthesis as well as with the antioxidative system. Genes which showed O(3)-dependent increases included FSCOMT (caffeic-acid O-methyltransferase) connected with lignin formation, the stress response genes FSACS2 (ACC synthase) and FSPR1 (PR10 - pathogenesis-related protein), as well as FSNCED1 (9-cis-epoxicarotenoid dioxygenase), the rate-limiting enzyme of the ABA synthesis. For FSNCED1 expression level, a significant O(3) effect was found with an 8-fold (sun) and 7 fold (shade) induction in July 2003 and a 3-fold and 2.5-fold induction in July 2004. While the observed effects were not continuous, elevated O(3) is concluded to have the potential to disrupt the defence and signalling system. PMID- 17357020 TI - Effects of long-term, free-air ozone fumigation on the cytokinin content of mature beech trees. AB - We present the results of a study of the effects of chronic exposure to elevated ozone on the cytokinins of mature beech trees. Methods for analysing the cytokinin (CK) content of beech (FAGUS SYLVATICA) were developed using seven enzyme-linked immunosorbent assays (ELISAs). Samples taken during 2003 and 2004 from 10 mature beech trees in Kranzberg forest, 5 trees exposed to twice ambient ozone (2 x O(3)) by free-air fumigation and 5 control trees (1 x O(3)), were analysed. In 2003 and 2004 the cytokinin content of leaf samples followed a similar seasonal pattern. In leaf samples, the content of aromatic types was equal to that of the isoprenoid types. In root samples, the level of aromatic types was no different from leaves, but that of the isoprenoid types was much higher. Leaf and phloem cytokinin contents for 2 x O(3) trees were lower than for 1 x O(3) at almost all sampling times. The effect of ozone was greater for leaves in the sun crown than for leaves in the shade crown. By contrast, the root and xylem contents of cytokinin for 2 x O(3) trees were greatly elevated over the values for 1 x O(3) trees early in the growing season. We propose that O(3) associated CK destruction in leaves reduces CK-mediated root growth suppression. The resulting increases in root growth and ectomycorrhiza, reported by other groups in the Kranzberg forest project, are likely to be responsible for the increased CK export in xylem, although O(3)-associated CK destruction in the leaves appears to nullify this increase. PMID- 17357021 TI - Gas exchange and antioxidative compounds in young beech trees under free-air ozone exposure and comparisons to adult trees. AB - Three-year-old beech (Fagus sylvatica) seedlings growing in containers were placed into the sun and shade crown of a mature beech stand exposed to ambient (1 x O(3)) and double ambient (2 x O(3)) ozone concentrations at a free-air exposure system ("Kranzberg Forst", Germany). Pigments, alpha-tocopherol, glutathione, ascorbate, and gas exchange were measured in leaves during 2003 (a drought year) and 2004 (an average year). Sun-exposed seedlings showed higher contents of antioxidants, xanthophylls, and beta-carotene and lower contents of chlorophyll, alpha-carotene, and neoxanthin than shade-exposed seedlings. In 2003 sun-exposed seedlings showed higher contents of carotenoids and total glutathione and lower net photosynthesis rates (A(max)) compared to 2004. O(3) exposure generally affected the content of chlorophyll, the xanthophyll cycle, and the intercellular CO(2) concentration (c(i)). Seedlings differed from the adjacent adult trees in most biochemical and physiological parameters investigated: Sun exposed seedlings showed higher contents of alpha-tocopherol and xanthophylls and lower contents of ascorbate, chlorophyll, neoxanthin, and alpha-carotene compared to adult trees. Shade exposed seedlings had lower contents of xanthophylls, alpha-carotene, and alpha-tocopherol than shade leaves of old-growth trees. In 2003, seedlings had higher A(max), stomatal conductance (g(s)), and c(i) under 2 x O(3) than adult trees. The results showed that shade acclimated beech seedlings are more sensitive to O(3), possibly due to a lower antioxidative capacity per O(3) uptake. We conclude that beech seedlings are uncertain surrogates for adult beech trees. PMID- 17357022 TI - CASIROZ: Root parameters and types of ectomycorrhiza of young beech plants exposed to different ozone and light regimes. AB - Tropospheric ozone (O(3)) triggers physiological changes in leaves that affect carbon source strength leading to decreased carbon allocation below-ground, thus affecting roots and root symbionts. The effects of O(3) depend on the maturity related physiological state of the plant, therefore adult and young forest trees might react differently. To test the applicability of young beech plants for studying the effects of O(3) on forest trees and forest stands, beech seedlings were planted in containers and exposed for two years in the Kranzberg forest FACOS experiment (Free-Air Canopy O(3) Exposure System, http://www.casiroz.de ) to enhanced ozone concentration regime (ambient [control] and double ambient concentration, not exceeding 150 ppb) under different light conditions (sun and shade). After two growing seasons the biomass of the above- and below-ground parts, beech roots (using WinRhizo programme), anatomical and molecular (ITS-RFLP and sequencing) identification of ectomycorrhizal types and nutrient concentrations were assessed. The mycorrhization of beech seedlings was very low ( CA. 5 % in shade, 10 % in sun-grown plants), no trends were observed in mycorrhization (%) due to ozone treatment. The number of Cenococcum geophilum type of ectomycorrhiza, as an indicator of stress in the forest stands, was not significantly different under different ozone treatments. It was predominantly occurring in sun-exposed plants, while its majority share was replaced by Genea hispidula in shade-grown plants. Different light regimes significantly influenced all parameters except shoot/root ratio and number of ectomycorrhizal types. In the ozone fumigated plants the number of types, number of root tips per length of 1 to 2 mm root diameter, root length density per volume of soil and concentration of Mg were significantly lower than in control plants. Trends to a decrease were found in root, shoot, leaf, and total dry weights, total number of root tips, number of vital mycorrhizal root tips, fine root (mass) density, root tip density per surface, root area index, concentration of Zn, and Ca/Al ratio. Due to the general reduction in root growth indices and nutrient cycling in ozone-fumigated plants, alterations in soil carbon pools could be predicted. PMID- 17357023 TI - Evidence that branch cuvettes are reasonable surrogates for estimating O3 effects in entire tree crowns. AB - Within the scope of quantifying ozone (O(3)) effects on forest tree crowns it is still an open question whether cuvette branches of adult trees are reasonable surrogates for O(3) responses of entire tree crowns and whether twigs exhibit autonomy in defense metabolism in addition to carbon autonomy. Therefore, cuvette enclosed branches of mature beech (Fagus sylvatica) trees were compared with branches exposed to the same and different ozone regimes by a free-air fumigation system under natural stand conditions by means of a VICE VERSA experiment. For this purpose, cuvettes receiving 1 x O(3) air were mounted in trees exposed to 2 x O(3) and cuvettes receiving 2 x O(3) air were mounted in trees exposed to 1 x O (3) in the upper sun crown. At the end of the fumigation period in September 2004, leaves were examined for differences in gas exchange parameters, pigments, antioxidants, carbohydrates, and stable isotope ratios. No significant differences in foliar gas exchange, total carbohydrates, stable isotope ratios, pigment, and antioxidant contents were found as a consequence of cuvette enclosure (cuvette versus free-air branches) of the same O(3) concentrations besides increase of glucose inside the cuvettes and reduction of the de epoxidation state of the xanthophyll cycle pigments. No significant ozone effect was found for the investigated gas exchange and most biochemical parameters. The total and oxidized glutathione level of the leaves was increased by the 2 x O(3) treatment in the cuvette and the free-air branches, but this effect was significant only for the free-air branches. From these results we conclude that cuvette branches are useful surrogates for examining the response of entire tree crowns to elevated O(3) and that the defence metabolism of twigs seems to be at least partially autonomous. PMID- 17357024 TI - Modelling ozone effects on adult beech trees through simulation of defence, damage, and repair costs: Implementation of the CASIROZ ozone model in the ANAFORE forest model. AB - Ozone affects adult trees significantly, but effects on stem growth are hard to prove and difficult to correlate with the primary sites of ozone damage at the leaf level. To simulate ozone effects in a mechanistic way, at a level relevant to forest stand growth, we developed a simple ozone damage and repair model (CASIROZ model) that can be implemented into mechanistic photosynthesis and growth models. The model needs to be parameterized with cuvette measurements on net photosynthesis and dark respiration. As the CASIROZ ozone sub-model calculates effects of the ozone flux, a reliable representation of stomatal conductance and therefore ozone uptake is necessary to allow implementation of the ozone sub-model. In this case study the ozone sub-model was used in the ANAFORE forest model to simulate gas exchange, growth, and allocation. A preliminary run for adult beech (FAGUS SYLVATICA) under different ozone regimes at the Kranzberg forest site (Germany) was performed. The results indicate that the model is able to represent the measured effects of ozone adequately, and to distinguish between immediate and cumulative ozone effects. The results further help to understand ozone effects by distinguishing defence from damage and repair. Finally, the model can be used to extrapolate from the short-term results of the field study to long-term effects on tree growth. The preliminary simulations for the Kranzberg beech site show that, although ozone effects on yearly growth are variable and therefore insignificant when measured in the field, they could become significant at longer timescales (above 5 years, 5 % reduction in growth). The model offers a possible explanation for the discrepancy between the significant effects on photosynthesis (10 to 30 % reductions simulated), and the minor effects on growth. This appears to be the result of the strong competition and slow growth of the Kranzberg forest, and the importance of stored carbon for the adult beech (by buffering effects on carbon gain). We finally conclude that inclusion of ozone effects into current forest growth and yield models can be an important improvement into their overall performance, especially when simulating younger and less dense forests. PMID- 17357025 TI - Suitability of a combined stomatal conductance and photosynthesis model for calculation of leaf-level ozone fluxes. AB - Currently, the most important source of uncertainty in stomatal ozone flux ( FO3) modelling is the stomatal conductance ( gst) factor. Hence FO3 model accuracy will strongly depend on the gst model being implemented. In this study the recently developed semi-empirical Gst model of Dewar was coupled to the widely known biochemical photosynthesis ( An) model of Farquhar. The Gst performance of this model combination was evaluated with a 4-month time series of beech ( Fagus sylvatica L.) measurements. The Gst model was hereto optimized in two steps to a 4-day and a 8-day period. A comparison between the modelled and measured gst to O(3) (gstO3) revealed a rather good overall performance (R(2)=0.77). Errors between the model combination and the measurements are thought to be largely caused by a moderate performance of the AN model, due to poor parameterization. Two 2-day periods with distinctly differing soil and meteorological conditions were chosen to give a picture of the daily gst performance. Although instant relative differences between modelled and measured gstO3 are sometimes high, the model combination is able to simulate the rough daily courses of gstO3 and hence FO3 reasonably well. Further improvement on full parameterization of the gst model and a well-parameterized An model to be linked to are needed to draw founded conclusions about its performance. Future efforts hereto are certainly justified since the model's mechanistic nature makes it a tool able to model gst variation in space and time, O(3) effects on gst, and effective FO3. PMID- 17357026 TI - [Interventions for caregivers of stroke patients: need and effectiveness]. AB - After discharge from hospital most stroke patients are being cared for by relatives. In the majority of cases it does mean long-term demands for relatives and often it has also an effect on their health. There is a variety of possibilities for offering support to relatives in accomplishing their tasks and thus contribute to a relief of burden. There has not yet been enough research investigating how various intervention concepts really meet the needs of the relatives and how effective the interventions reduce the burden of the caregivers. Five types of intervention concepts for supporting relatives of stroke patients can be differentiated so far: special services, training, counselling, social support through other caregivers and multi-component interventions. On the basis of 42 intervention studies an attempt is being made to give a preliminary statement about the effectiveness of intervention models. The multi-component interventions combined with psychotherapeutic strategies seem to emerge as a recommendable concept. PMID- 17357028 TI - [Mourning after perinatal death--prevalence symptoms and treatment--a review of the literature]. AB - Miscarriage and perinatal loss are associated with considerable psychosocial distress. A substantial proportion of women who suffered the loss of a child develop a psychological disorder. Depression, anxiety disorder, post-traumatic stress disorder and somatoform disorder all have been linked in various studies to grief reactions in response to perinatal loss. A number of studies based on clinical and empirical evidence suggest various therapeutic procedures. However, a current Cochrane review fails to provide empirical evidence favouring a specific treatment strategy. In Germany in routine care in gynaecology no psychological support is offered to women suffering from grief reactions due to perinatal loss. Further research is needed to develop evidence based treatment strategies for secondary prevention in this field. PMID- 17357029 TI - [Skill training and the post-treatment efficacy of dialectic behavior therapy six month after discharge of the hospital]. AB - Patients with borderline personality disorder (BPD) are getting significantly better under inpatient Dialectic Behavioral Therapy (DBT). Several studies have shown the efficacy of DBT inpatient treatment for patients with BPD. Signs of the efficacy of DBT are mainly reduction of self-injurious behaviour and suicidality as well as reduction of clinical parameters such as depression and general symptom stress (SCL-90-R). In this catamnestic study we evaluated 38 former DBT inpatients for continuous treatment effects of DBT. The results showed a significant reduction in depression as well as general symptom stress up to 6 month after discharge. Furthermore, these effects were positively correlated with the continuous use of DBT-skills 1 and 6 months after discharge. These skills are central part of DBT-treatment and are especially useful for managing high tension, suicidality and self-injurious behaviour. Therefore, the use of skills is possibly the reason for the continuous effect of DBT after the end of inpatient treatment. PMID- 17357030 TI - [Validating the efficacy of a group intervention program on the quality of life of depressed patient's spouses]. AB - A new group intervention program has been assessed, rating its ability to increase the quality of life in partners of patients suffering under depression. Over a period of six months 66 subjects participated in an intervention group for a total of twelve sessions. The control group consisted of 50 persons, and quality of life was assessed with the WHOQOL-BREF. The five WHOLQOL domains were used as independent variables in random-effects regression models measuring the time effect. Although the quality of life of the subjects was below that of the general population at the beginning of the intervention, the study resulted in no significant improvement in quality of life. In contrast, satisfaction of participants with the intervention was high. PMID- 17357031 TI - [One drink, one drunk--controlled drinking by alcoholics? 3-year-outcome after intensive outpatient treatment]. AB - BACKGROUND: Up to now, controlled drinking as an alternative to abstinence for alcohol-dependents has been discussed controversially. In the present study we examined in a sample of alcohol-dependent patients whether or not controlled drinking is possible during a three years period following treatment. METHODS: 103 consecutively recruited alcohol-dependent participants (ICD-10) which took part in an abstinence-orientated outpatient treatment were re-interviewed 6, 12, 24, 36 months following treatment (follow-up ratio ca. 90 %). RESULTS: Analysis revealed that 43 % of patients were abstinent during total follow-up period and 12 % of patients were classified as improved at follow-up using the classification proposed by Feuerlein and Kufner. Of these patients, no patient at all was able to practise self-controlled drinking alcohol during the entire follow-up period. CONCLUSIONS: Only four patients had a drinking pattern similar to controlled drinking during a maximum period of 24 months. Though the primary aim of the evaluated outpatient clinic was to achieve abstinence and not controlled drinking, controlled drinking in alcohol-dependent patients nevertheless seems to be a rare phenomenon, which cannot be recommended. Moreover, recent animal models for alcoholism indicate alcoholism being an irreversible pattern. PMID- 17357032 TI - Deficit in memory consolidation (abnormal forgetting rate) in childhood temporal lobe epilepsy. Pre and postoperative long-term observation. AB - Deficits in memory consolidation have been reported in adult patients with epilepsy but, not to our knowledge, in children. We report the long-term follow up (9 y. o. to 18 y. o.) of a boy who suffered from temporal lobe epilepsy and underwent a left temporal lobectomy with amygdalo-hippocampal resection at the age of 10. He showed an abnormal forgetting rate when trying to encode new information and a significant deficit for retrieving remote episodic memories (when compared with his twin brother), both consistent with a consolidation disorder. His memory condition slightly improved after cessation of the epilepsy, nevertheless did not normalize. No standard memory assessment could pinpoint his memory problem, hence an adapted methodology was needed. We discuss the nature of the memory deficit, its possible causes and its clinical implications. PMID- 17357033 TI - Topiramate in the treatment of highly refractory patients with Dravet syndrome. AB - The purpose of this study was to assess the effectiveness and tolerability of topiramate (TPM) as add-on therapy in children with Dravet syndrome and considered unsatisfactorily controlled using stiripentol. All the 36 patients having been treated with TPM in our centre in 2001 were retrospectively evaluated. Seventy percent of them still received stiripentol when TPM was introduced. The association of both drugs did not need any particular adaptation of dosages. The mean TPM follow-up was 13.3 months (4-25 months) and the mean optimal TPM dose was 3.2 mg/kg/d (0.6-9.2 mg/kg/d). Twenty eight children (78 %) showed more than 50 % reduction in the frequency of generalized tonic-clonic seizures and status epilepticus (SE), whereas 8 % had more than 50 % increase. Six patients (17 %) remained seizure-free for at least 4 months. The most frequently reported side-effects were gastrointestinal and behavioural disturbances. TPM had to be stopped in 17 % of patients, because of poor tolerability and/or lack of efficacy. Topiramate seems therefore to be helpful in Dravet syndrome, even in patients not satisfactorily controlled by stiripentol. Both drugs can be easily and safely associated. PMID- 17357034 TI - Disabilities in children with hydrocephalus--a population-based study of children aged between four and twelve years. AB - BACKGROUND: Children with hydrocephalus represent a heterogeneous group with various aetiologies and disability profiles. Over the years, continuous changes in medical care have occurred and updated information is important. AIM: To study disability profiles in aetiological and gestational age subgroups of children with hydrocephalus in the 1990s. METHOD: A population-based series of 114 children, 70 with infantile hydrocephalus and 44 with hydrocephalus associated with MMC. All the children were examined clinically and interviewed. RESULTS: Learning disabilities were present in 47 % of children with infantile hydrocephalus compared with 16 % of those with MMC, cerebral palsy in 27 % vs. zero and epilepsy in 34 vs. 11 %. Even after excluding children with cerebral palsy, the majority had abnormal tendon reflexes and scored below the 5th centile on a motor test. Hydrocephalus overt at birth, low gestational age, a perinatal origin, enlarged ventricles at follow-up and several shunt revisions all indicated risk factors for a poor outcome. CONCLUSIONS: In spite of major advances in management, hydrocephalus in children still has a considerable impact on outcome. Being born very preterm and with a hydrocephalus that is already overt at birth involve the highest risk of a poor outcome. Apart from major impairments, the children frequently have definite motor problems. PMID- 17357035 TI - Serial quantitative diffusion tensor MRI of the term neonates with hypoxic ischemic encephalopathy (HIE). AB - AIM: To determine the altered pattern of fractional anisotropy (FA) and mean diffusivity (MD) change in brain parenchyma in serially studied neonates with mild or moderate hypoxic ischemic injury (HIE) within 7 days after birth and again at the age of three months. METHODS: Serial diffusion tensor imaging (DTI) was performed at two-time points in term neonates with mild (n = 7) and moderate (n = 10) HIE and age/sex-matched controls (n = 7). Neurodevelopmental outcome was assessed at the time of the 2nd study. RESULTS: On comparing FA and MD changes over time using two-way analysis of variance between neonates with HIE and controls, we observed significant differences in age-related FA increase (p < 0.05) in anterior limb of internal capsule and periventricular white matter of parietal, occipital, and temporal lobes. Significant differences in age-related MD decrease (p < 0.05) was observed in the caudate nuclei, and temporal white matter among these groups. Significant positive correlation was observed between neurodevelopmental outcome and FA. CONCLUSION: The results suggest that abnormal FA and MD values help in early and more accurate assessment of microstructural damage in HIE that may have predictive value for long-term neurofunctional outcome in these neonates. PMID- 17357036 TI - Treatment of spastic equinus gait with botulinum toxin A: Does dose matter? Analysis of a clinical cohort. AB - INTRODUCTION: This study reports the effects of various doses of BTX-A when treating equinus gait in cerebral palsy in a clinical setting at a tertiary hospital. PATIENTS: Twenty-nine children with CP (age 1.5-9.6 yrs, GMFCS I-IV) met the preset inclusion criteria. The treatment episodes per child ranged from 1 to 5 and the effects on a total of 80 legs in 55 treatment sessions were evaluated. METHODS: BTX-A doses injected into the gastroc-soleus muscle were divided into low- ( 6 units/kg bw) dose groups. The outcome measurements included active and passive ankle range of movement, Modified Ashworth Scale, dynamic muscle length, Selective Motor Control score, Observational Gait Scale score, and Goal Attainment Scale score at pre-treatment and 1, 2, and 4 months post-treatment. RESULTS: The only differences between the treatment groups were observed at 2 and 4 months in terms of change in passive ankle ROM and at 4 months in change in selective dorsiflexion, favouring the low dose group. The incidence and severity of side-effects did not differ between the groups. CONCLUSION: Doses over 6 units/kg bw injected into the gastroc-soleus muscle do not necessarily yield superior results compared with lower doses. PMID- 17357037 TI - Impact of surgery and adjuvant therapy on balance function in children and adolescents with cerebellar tumors. AB - OBJECTIVES: This study examined the effects of posterior fossa tumor surgery and concomitant irradiation and/or chemotherapy on the long-term recovery of balance function in children and adolescent patients. SUBJECTS AND METHODS: 22 patients, treated during childhood for a benign (n = 14) or malignant cerebellar tumor (n = 8), were examined in chronic state (mean latency between surgery and testing: 7.7 years, range 3 - 17 years). Postural impairments were assessed with static and dynamic posturography. All cerebellar lesions were documented by standardized and normalized MRI data. Healthy age- and gender-matched subjects served as a control group. RESULTS: Comparing the balance function of (i) children with or without affected cerebellar nuclei and (ii) children with and without adjuvant chemotherapy and/or radiotherapy revealed that damage to the cerebellar nuclei had more impact on neurological impairment than concomitant tumor therapy. Balance abnormalities were most pronounced when a lesion affected the fastigial nucleus. Chemotherapy with its neurological side effect was associated with enhanced postural sway in only two children with malignant tumors. CONCLUSIONS: The study results indicate that the sparing of the deep cerebellar nuclei had the greatest impact on the recovery of balance function in pediatric patients treated for both a benign or malignant cerebellar tumor. PMID- 17357038 TI - The clinical characterizations of benign partial epilepsy in infancy. AB - The aim of this study is to clarify the detailed clinical features of benign partial epilepsy in infancy. The subject of the study was 33 patients with benign partial epilepsy in infancy confirmed by a long-term follow-up beyond 8 years of age. The data were obtained from medical records of the patients in combination with the data obtained from telephone interview. The median age at the first and last seizure was 5 and 8 months, respectively. In 26 patients, seizures disappeared within 3 months after the onset. Family history of benign partial epilepsy in infancy was seen in 17 patients. The median number of seizures was 7. A cluster of seizures was observed in 26 patients. The type of seizures was complex partial seizures alone in 6 patients, secondarily generalized seizures alone in 9, and both types in 18. Decreased responsiveness, lateral eye deviation, and cyanosis were commonly observed. Initial interictal electroencephalograms were normal in all patients. However, paroxysmal discharges were recognized in 2 patients in the second EEG during the first year of life. The main features of benign partial epilepsy in infancy were a high incidence of a cluster of seizures, short persistence of seizures, and normal initial interictal EEGs. PMID- 17357039 TI - Moyamoya syndrome after cranial irradiation for bone marrow transplantation in a patient with acute leukemia. AB - It is well known that radiation-induced vasculopathy and arteritis are two of the complications of whole brain radiation therapy. Moyamoya syndromes after cranial irradiation among patients with brain tumors were previously reported. However, we could find only three cases of prophylactic cranial irradiation for hematological disorders and no case of cranial irradiation before bone marrow transplantation in patients with acute leukemia. We recently treated a boy who developed moyamoya vessels 1.5 years after cranial irradiation for bone marrow transplantation for acute leukemia. This is the first report of moyamoya syndrome after cranial irradiation for bone marrow transplantation. The mechanism and incidence of vasculopathy after cranial irradiation are unclear. It would be useful to accumulate data and reveal the etiology of moyamoya vessels formation after cranial irradiation. PMID- 17357041 TI - Severe dengue virus infection in travelers. PMID- 17357042 TI - A new direction in understanding the pathogenesis of respiratory syncytial virus bronchiolitis: how real infants suffer. PMID- 17357043 TI - HIV-1 viral dynamics studies in the setting of clinical trials--A window of opportunity. PMID- 17357044 TI - Severe dengue virus infection in travelers: risk factors and laboratory indicators. AB - BACKGROUND: Dengue fever is the most common arboviral disease in travelers. In countries where dengue virus is endemic, sequential (secondary) infections with different dengue virus serotypes are associated with disease severity. Data on severity and secondary infection rates in a population of travelers are lacking. METHODS: Intensified surveillance of dengue fever in travelers was performed within the European Network on Surveillance of Imported Infectious Diseases. Data were collected at 14 European clinical referral centers between 2003 and 2005. RESULTS: A total of 219 dengue virus infections imported from various regions of endemicity were reported. Serological analysis revealed a secondary immune response in 17%. Spontaneous bleeding was observed in 17 (8%) patients and was associated with increased serum alanine and aspartate aminotransferase levels and lower median platelet counts. Two (0.9%) patients fulfilled the World Health Organization (WHO) case definition for dengue hemorrhagic fever. However, 23 (11%) travelers had severe clinical manifestations (internal hemorrhage, plasma leakage, shock, or marked thrombocytopenia). A secondary immune response was significantly associated with both spontaneous bleeding and other severe clinical manifestations. CONCLUSIONS: In travelers, severe dengue virus infections are not uncommon but may be missed if the WHO classification is strictly applied. High liver enzyme levels and low platelet counts could serve as indicators of disease severity. PMID- 17357046 TI - Antibody-dependent cellular cytotoxicity mediated by plasma obtained before secondary dengue virus infections: potential involvement in early control of viral replication. AB - BACKGROUND: Preexisting dengue virus (DV)-specific antibodies from prior heterologous DV infection may have several effects in secondary DV infection. These antibodies may mediate protective effects by means of antibody-dependent cellular cytotoxicity (ADCC), in which virus-specific antibodies bind to the surface of heterologous DV-infected cells and mediate natural killer cell lysis. In the present study, we examined the ability of plasma obtained before secondary DV infection to induce ADCC of DV-infected cells. METHODS: Plasma samples were obtained before DV2 or DV3 infection in a prospective cohort study of Thai schoolchildren. The ADCC activity in the plasma samples was measured by (51)Cr release assay, using persistently DV2- or DV3-infected Raji cells as targets. RESULTS: ADCC activity in plasma obtained before secondary infection directly correlated with neutralizing antibody titers, anti-DV immunoglobulin G1 levels, and a multitypic 50% plaque reduction neutralization test pattern. ADCC activity in pre-secondary DV3 infection plasma samples inversely correlated with plasma viremia levels, but no such correlation was seen in pre-secondary DV2 infection plasma samples. ADCC activity did not correlate with disease severity in subsequent secondary DV2 or DV3 infection but was lowest in plasma from patients with dengue hemorrhagic fever due to secondary DV3 infection. CONCLUSIONS: ADCC may contribute to the early control of secondary DV3 viremia in vivo. PMID- 17357045 TI - Patterns of host genome-wide gene transcript abundance in the peripheral blood of patients with acute dengue hemorrhagic fever. AB - Responses by peripheral blood leukocytes may contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We used DNA microarrays to reveal transcriptional patterns in the blood of 14 adults with DHF. Acute DHF was defined by an abundance of transcripts from cell cycle- and endoplasmic reticulum (ER)-related genes, suggesting a proliferative response accompanied by ER stress. Transcript abundance levels for immunoresponse-associated genes, including cell surface markers, immunoglobulin, and innate response elements, were also elevated. Twenty four genes were identified for which transcript abundance distinguished patients with dengue shock syndrome (DSS) from those without DSS. All the gene transcripts associated with DSS, many of which are induced by type I interferons, were less abundant in patients with DSS than in those without DSS. To our knowledge, these data provide the first snapshot of gene-expression patterns in peripheral blood during acute dengue and suggest that DSS is associated with attenuation of selected aspects of the innate host response. PMID- 17357047 TI - Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993-2003. AB - Recently a new rotavirus vaccine was licensed in the United States and recommended for universal immunization of American children. The impact of the vaccine on a decrease in hospitalizations will take several years to assess and will be based on the availability of good baseline data on the disease. We used the largest US hospital discharge database available, the Healthcare Cost and Utilization Project (HCUP), to study national rates, trends, and risk factors for diarrhea- and rotavirus-associated hospitalizations and deaths among children <5 years of age, to establish a baseline against which vaccine implementation can be measured. Rotavirus remained the most important cause of pediatric diarrhea throughout the study period (1993-2003). When the data were extrapolated to the US population, rotavirus was estimated to be the cause of approximately 60,000 hospitalizations and 37 deaths annually. Black infants had a significantly higher risk of being hospitalized with and dying from rotavirus disease early in life, compared with white infants (risk ratio [RR] for hospitalization by 12 months of age was 2.4, with a 95% confidence interval [CI] of 1.2-4.7; RR for death was 2.0, with a 95% CI of 1.7-2.5). Such racial differences in age and risk of rotavirus-associated hospitalization and death highlight the importance of timely and early rotavirus immunization of minority children. The HCUP database serves as a sensitive and robust data source for monitoring the impact of a rotavirus immunization program in the United States. PMID- 17357048 TI - Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. AB - BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. METHODS: We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3. RESULTS: Quantities of lymphocyte derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8 positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. CONCLUSIONS: Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis. PMID- 17357049 TI - Inhibition of rhinovirus replication in vitro and in vivo by acid-buffered saline. AB - Human rhinoviruses (HRVs) are quite sensitive to low pH. To determine whether this characteristic might be a therapeutic target, we evaluated the sensitivity of HRV to low-pH buffers in vitro and in vivo. Our findings confirm that low pH inhibited replication of most HRVs and reduced the replication of influenza virus. Preliminary experiments verified that the surface pH of the human nasopharynx could be transiently lowered to pH approximately 4.0 by topical administration of citrate/phosphate (CP) buffers, which was well tolerated. In a pilot experimental colds study, intranasal administration of CP buffer, compared with normal saline, reduced viral shedding by 1 log unit (10(3) vs. 10(4) 50% tissue culture infective dose/mL; P<.01), although respiratory symptoms were not significantly reduced. These findings demonstrate that low-pH buffers have antiviral activity in vivo and suggest that a larger clinical trial is warranted to determine whether this approach could reduce rates of viral transmission. PMID- 17357050 TI - Effects of aerosolized rabies virus exposure on bats and mice. AB - Between 1956 and 1977, 4 human cases of rabies virus infection were attributed to aerosolized rabies virus; however, little work has been done to address this topic since the late 1960s. Employing modern nebulization equipment coupled with serologic, cell culture, and molecular technology, we have continued the investigation into aerosolized rabies virus as a potential route of transmission. Laboratory mice and 2 species of bats were exposed, through aerosol, to 3 variants of rabies virus. All bats survived exposure to aerosolized rabies virus and produced rabies neutralizing antibody. Several mice died of rabies as a result of aerosol exposure. Antibody response was followed for 6 months before animals were given an intramuscular challenge of rabies virus. Poor protection from challenge was afforded in bats, despite the presence of neutralizing antibodies. PMID- 17357051 TI - Immunological memory after exposure to variola virus, monkeypox virus, and vaccinia virus. AB - We compared cellular and humoral immunity to vaccinia virus (VV) in individuals exposed to 3 different orthopoxviruses: 154 individuals previously vaccinated with VV, 7 individuals with a history of monkeypox virus infection, and 8 individuals with a history of variola virus infection. Among individuals vaccinated >20 years prior, 9 (14%) of 66 individuals demonstrated VV-specific interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay responses; 21 (50%) of 42 had lymphoproliferative (LP) responses, and 29 (97%) of 30 had VV specific neutralizing antibodies. One year after monkeypox virus infection, 6 of 7 individuals had IFN- gamma ELISPOT responses, all had VV-specific LP responses, and 3 of 7 had VV-specific neutralizing antibodies. Of 8 individuals with a history of variola virus infection, 1 had a VV-specific IFN- gamma ELISPOT response, 4 had LP responses against whole VV, 7 had LP responses against heat denatured vaccinia antigen, and 7 had VV-specific neutralizing antibodies. Survivors of variola virus infection demonstrated VV-specific CD4 memory cell responses and neutralizing antibodies >40 years after infection. PMID- 17357052 TI - Expression of ICP0 is sufficient to trigger natural killer cell recognition of herpes simplex virus-infected cells by natural cytotoxicity receptors. AB - Natural killer (NK) cells are an important component of the immune response to a number of viruses; however, the molecular basis of how NK cells discriminate between healthy and virus-infected cells is largely unknown. Here, we show that expression of the immediate-early gene product ICP0 is sufficient to produce an increased susceptibility to NK lysis of herpes simplex virus (HSV)-infected cells. This effect does not depend on down-regulation of major histocompatibility complex class I molecules or on the induction of expression of ligands for the activating NKG2D receptor. Detection by NK cells of the changes in the target cell induced by HSV ICP0 gene expression depends on the natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46. To our knowledge, this is the first identification of a viral gene that triggers the up-regulation of cellular ligands for the NCR; moreover, these observations highlight the importance of the NCR for immunosurveillance of viral infection by NK cells. PMID- 17357053 TI - Plasma HIV-1 RNA dynamics in antiretroviral-naive subjects receiving either triple-nucleoside or efavirenz-containing regimens: ACTG A5166s. AB - OBJECTIVE: We sought to compare clearance rates of plasma human immunodeficiency virus type 1 (HIV-1) RNA in men and women starting triple-nucleoside-based versus efavirenz (EFV)-based regimens. METHODS: First- and second-phase decay rates of plasma HIV-1 were compared in men and women initiating a triple nucleoside reverse-transcriptase inhibitor (NRTI) regimen versus regimens that included EFV plus an NRTI. Subjects (n=64) were randomized to receive zidovudine/lamivudine/abacavir (triple-nucleoside regimen), zidovudine/lamivudine plus EFV (3-drug EFV regimen) or zidovudine/lamivudine/abacavir plus EFV (4-drug EFV regimen). Plasma HIV-1 RNA levels were fitted to a biexponential viral dynamics model using a nonlinear mixed-effects model. Nonparametric Wilcoxon tests compared empirical Bayes estimates of first- and second-phase viral decay rates between treatment arms and sex. RESULTS: Median first-phase viral decay rates were significantly faster in subjects receiving the 3-drug EFV regimen (0.67/day), compared with those receiving the triple-nucleoside regimen (0.56/day; P=.02). The second-phase viral decay rate was also faster in the 3 drug EFV group than in the triple-nucleoside group (P=.09). Decay rates in the 4 drug EFV group were intermediate. Viral decay rates were not significantly different in men and women. CONCLUSIONS Faster initial viral decay in subjects randomized to a 3-drug EFV-based regimen corresponded to the overall superior efficacy of that regimen. Viral decay rates did not differ by sex. PMID- 17357054 TI - HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads. AB - We investigated the effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression among 145 Kenyan women followed from the time of HIV-1 acquisition. Compared with those infected with subtype A, women infected with subtype D had higher mortality (hazard ratio, 2.3 [95% confidence interval, 1.0 5.6]) and a faster rate of CD4 cell count decline (P=.003). The mortality risk persisted after adjustment for plasma HIV-1 load. There were no differences in plasma viral load by HIV-1 subtype during follow-up. HIV-1 subtype D infection is associated with a >2-fold higher risk of death than subtype A infection, in spite of similar plasma HIV-1 loads. PMID- 17357055 TI - Treatment of chronic hepatitis B or C in HIV-infected patients with dual viral hepatitis. AB - Dual chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are recognized in 3%-5% of human immunodeficiency virus (HIV)-infected individuals. More severe liver disease is seen in these patients. Viral interference may account for the fact that replication of one virus generally predominates over replication of the other. The impact that treatment of HBV or HCV infection has on this reciprocal inhibition is not well established. No evidence of reactivation of either HBV or HCV was seen when complete suppression of the other predominant virus was achieved with specific therapy in 21 subjects with HIV infection and dual HBV/HCV infections. This information has important pathogenic implications and may influence therapeutic decisions. PMID- 17357056 TI - Mucosal administration of low-dose cell-associated feline immunodeficiency virus promotes viral latency. AB - Human immunodeficiency virus type 1 can occasionally be detected as a cryptic or latent infection in seronegative, asymptomatic patients. To develop an animal model of host latency, cats were mucosally challenged with 10(2)-10(6) feline immunodeficiency virus (FIV)-infected T cells. Although high-dose exposure (10(4) 10(6) T cells) resulted in progressive infection, no evidence of infection was seen in 5 of 6 cats exposed to 10(2) or 10(3) T cells. However, after ex vivo CD8(+) T cell depletion and phorbol myristate acetate treatment, FIV could be reactivated in tissues from 4 cats. Thus, latent tissue viral reservoirs can be induced by low-dose cell-associated mucosal challenge, providing a model to dissect the mechanisms that control reservoir establishment. PMID- 17357057 TI - MyD88-dependent immune response contributes to hearing loss in experimental pneumococcal meningitis. AB - Hearing loss is one of the most common sequelae in survivors of pneumococcal meningitis, affecting up to 26% of them. Here, we established the first mouse model of meningitis-associated hearing loss and investigated the role played by the Toll-like receptor-associated adapter molecule MyD88. C57BL/6 mice were infected intracisternally by Streptococcus pneumoniae. By use of audiometry and histological analysis, cochleae were assessed in uninfected control mice during the acute stage and after recovery. MyD88-deficient mice were analyzed 24 h after infection. Wild-type mice lost hearing capacity to a significant degree, which was accompanied by a granulocytic cochlear inflammation. After recovery, hearing loss was still evident, and spiral ganglion neuronal loss, hair cell damage, and fibrocytic occlusion of the cochlea were observed. In contrast, mice lacking MyD88 developed significantly less hearing loss and had diminished cochlear inflammation. Our results strongly suggest a proinflammatory role for MyD88 in the initiation of the inflammatory response during pneumococcal meningitis associated labyrinthitis. PMID- 17357058 TI - Low CD4 T cell immunity to pneumolysin is associated with nasopharyngeal carriage of pneumococci in children. AB - BACKGROUND: Recent studies in mice have suggested that T cell immunity may be protective against pneumococcal infection. METHODS: CD4 T cell proliferative responses to the pneumococcal proteins pneumolysin (Ply), Ply toxoid (F433), and choline-binding protein A were investigated in peripheral blood mononuclear cells (PBMCs) and adenoidal mononuclear cells (MNCs) obtained from children undergoing adenoidectomy. RESULTS: Ply and F433 induce significant proliferation of CD4 T cells in both PBMCs and adenoidal MNCs, and both memory and naive phenotypes of CD4 T cells proliferated after stimulation. In PBMCs, CD4 T cell proliferation induced by Ply and F433, which was associated with increased production of interferon (IFN)- gamma and tumor necrosis factor (TNF)- alpha , was significantly lower in children who were culture positive for pneumococcus than in those who were culture negative for pneumococcus (P<.05). Between groups, no such difference was observed in adenoidal MNC CD4 T cell proliferation, which was associated with production of IFN- gamma and interleukin (IL)-10. The CD4 T cell proliferation induced by Ply and F433 was inhibited by antibodies to Toll-like receptor 4. CONCLUSION: These data suggest that Ply induces CD4 T cell proliferative responses with production of IFN- gamma and TNF- alpha in PBMCs or of IFN- gamma and IL-10 in adenoidal MNCs, which may be important in modulating pneumococcal carriage in children. PMID- 17357059 TI - Killed but metabolically active Salmonella typhimurium: application of a new technology to an old vector. AB - Previous studies have shown that attenuated salmonellae utilized as vaccine vectors engender strong immune responses; however, balancing immunogenicity with reactogenicity remains problematic. Recent work in other bacteria has shown that photochemical treatment of DNA excision repair mutants ( Delta uvrAB) renders organisms "killed but metabolically active" (KBMA). Here, we extend this concept to Salmonella typhimurium. A strain of attenuated S. typhimurium previously evaluated in human volunteers was further deleted for uvrAB genes and designated CKS362. Photochemical treatment of CKS362 resulted in significant inactivation. These KBMA organisms were metabolically active as shown by radioactive methionine incorporation and lactate dehydrogenase activity. In mice inoculated intraperitoneally, KBMA CKS362 was markedly less reactogenic and stimulated a humoral immune equivalent to its live counterpart. Because the parental strain has previously been found to elicit strong immune responses to Salmonella antigens, we propose CKS362 as a prototype strain to test the immunogenicity of KBMA organisms in humans. PMID- 17357060 TI - Genotypes of the mannan-binding lectin gene and susceptibility to visceral leishmaniasis and clinical complications. AB - BACKGROUND: Visceral leishmaniasis (VL) is almost always lethal if not treated, but most infections with the causative agents are clinically silent. Mannan binding lectin (MBL), an opsonin, is a candidate molecule for modifying progression to VL because it may enhance infection with intracellular pathogens. Mutations in the MBL2 gene decrease levels of MBL and may protect against development of VL. This case-control study examines genotypes of MBL2 and levels of MBL in individuals presenting with different outcomes of infection with Leishmania chagasi. METHODS: Genotypes for MBL2 and levels of serum MBL were determined in uninfected control subjects (n=76) and in individuals presenting with asymptomatic infection (n=90) or VL (n=69). RESULTS: Genotypes resulting in high levels of MBL were more frequent (odds ratio [OR], 2.5 [95% confidence interval [CI], 1.3-5.0]; P=.006) among individuals with VL than among those with asymptomatic infections and were even more frequent (OR, 3.97 [95% CI, 1.10 14.38]; P=.043) among cases of VL presenting with clinical complications than among those with uneventful courses. Serum levels of MBL were higher (P=.011) in individuals with VL than in asymptomatic infections . CONCLUSIONS: Genotypes of the MBL2 gene predict the risk for developing VL and clinical complications in infections with L. chagasi. PMID- 17357061 TI - Population structure and transmission dynamics of Plasmodium vivax in rural Amazonia. AB - Understanding the genetic structure of malaria parasites is essential to predict how fast some phenotypes of interest originate and spread in populations. In the present study, we used highly polymorphic microsatellite markers to analyze 74 Plasmodium vivax isolates, which we collected in cross-sectional and longitudinal surveys performed in an area of low malaria endemicity in Brazilian Amazonia, and to explore the transmission dynamics of genetically diverse haplotypes or strains. P. vivax populations are more diverse and more frequently comprise multiple-clone infections than do sympatric Plasmodium falciparum isolates, but these features paradoxically coexist with high levels of inbreeding, leading to significant multilocus linkage disequilibrium. Moreover, the high rates of microsatellite haplotype replacement that we found during 15 months of follow-up most likely do not result from strong diversifying selection. We conclude that the small-area genetic diversity in P. vivax populations under low-level transmission is not severely constrained by the low rates of effective meiotic recombination, with clear public health implications. PMID- 17357062 TI - Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection. AB - BACKGROUND: Urinary tract infections (UTIs) are important causes of morbidity and death. The present study investigated whether genetic factors influence susceptibility to acute pyelonephritis (APN). CXCR1 expression was investigated as a factor predisposing to APN, because low CXCR1 expression has been associated with disease susceptibility in mice and disease-prone children. METHODS: The families of APN-prone children (n=130) and of age-matched control subjects without UTI (n=101) were studied. Three-generation pedigrees of UTI-associated morbidity were established by means of structured interviews of the families. CXCR1 expression was quantified by flow cytometric analysis of peripheral blood neutrophils obtained from family members and control subjects. RESULTS: APN was significantly more common in the family members of the APN-prone children (20 [15%] of 130 family members) than in the relatives of the control subjects (3 [3%] of 101 family members) (P<.002). Acute cystitis, in contrast, occurred with equal frequency in both groups (19%; P=1.0). Some families included many affected individuals, consistent with a dominant pattern of inheritance, whereas other families showed a recessive pattern of disease susceptibility. CXCR1 expression was significantly lower in the APN-prone children and in their relatives than in pediatric and adult control subjects (P<.0001). CONCLUSIONS: Our results suggest that susceptibility to APN is inherited and that low CXCR1 expression might predispose to disease. PMID- 17357063 TI - Polymerase chain reaction analysis for detecting capsule serotypes K1 and K2 of Klebsiella pneumoniae causing abscesses of the liver and other sites. PMID- 17357067 TI - Mendelian Inheritance in Man and its online version, OMIM. PMID- 17357068 TI - Overcoming the winner's curse: estimating penetrance parameters from case-control data. AB - Genomewide association studies are now a widely used approach in the search for loci that affect complex traits. After detection of significant association, estimates of penetrance and allele-frequency parameters for the associated variant indicate the importance of that variant and facilitate the planning of replication studies. However, when these estimates are based on the original data used to detect the variant, the results are affected by an ascertainment bias known as the "winner's curse." The actual genetic effect is typically smaller than its estimate. This overestimation of the genetic effect may cause replication studies to fail because the necessary sample size is underestimated. Here, we present an approach that corrects for the ascertainment bias and generates an estimate of the frequency of a variant and its penetrance parameters. The method produces a point estimate and confidence region for the parameter estimates. We study the performance of this method using simulated data sets and show that it is possible to greatly reduce the bias in the parameter estimates, even when the original association study had low power. The uncertainty of the estimate decreases with increasing sample size, independent of the power of the original test for association. Finally, we show that application of the method to case-control data can improve the design of replication studies considerably. PMID- 17357069 TI - Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux. AB - Congenital anomalies of the kidney and urinary tract (CAKUT) include vesicoureteral reflux (VUR). VUR is a complex, genetically heterogeneous developmental disorder characterized by the retrograde flow of urine from the bladder into the ureter and is associated with reflux nephropathy, the cause of 15% of end-stage renal disease in children and young adults. We investigated a man with a de novo translocation, 46,X,t(Y;3)(p11;p12)dn, who exhibits multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. This translocation disrupts ROBO2, which encodes a transmembrane receptor for SLIT ligand, and produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro. In addition, we identified two novel ROBO2 intracellular missense variants that segregate with CAKUT and VUR in two unrelated families. Adult heterozygous and mosaic mutant mice with reduced Robo2 gene dosage also exhibit striking CAKUT-VUR phenotypes. Collectively, these results implicate the SLIT-ROBO signaling pathway in the pathogenesis of a subset of human VUR. PMID- 17357070 TI - Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. AB - The duplication 17p11.2 syndrome, associated with dup(17)(p11.2p11.2), is a recently recognized syndrome of multiple congenital anomalies and mental retardation and is the first predicted reciprocal microduplication syndrome described--the homologous recombination reciprocal of the Smith-Magenis syndrome (SMS) microdeletion (del(17)(p11.2p11.2)). We previously described seven subjects with dup(17)(p11.2p11.2) and noted their relatively mild phenotype compared with that of individuals with SMS. Here, we molecularly analyzed 28 additional patients, using multiple independent assays, and also report the phenotypic characteristics obtained from extensive multidisciplinary clinical study of a subset of these patients. Whereas the majority of subjects (22 of 35) harbor the homologous recombination reciprocal product of the common SMS microdeletion (~3.7 Mb), 13 subjects (~37%) have nonrecurrent duplications ranging in size from 1.3 to 15.2 Mb. Molecular studies suggest potential mechanistic differences between nonrecurrent duplications and nonrecurrent genomic deletions. Clinical features observed in patients with the common dup(17)(p11.2p11.2) are distinct from those seen with SMS and include infantile hypotonia, failure to thrive, mental retardation, autistic features, sleep apnea, and structural cardiovascular anomalies. We narrow the critical region to a 1.3-Mb genomic interval that contains the dosage-sensitive RAI1 gene. Our results refine the critical region for Potocki-Lupski syndrome, provide information to assist in clinical diagnosis and management, and lend further support for the concept that genomic architecture incites genomic instability. PMID- 17357071 TI - Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease. AB - A susceptibility locus for coronary artery disease (CAD) has been mapped to chromosome 3q13-21 in a linkage study of early-onset CAD. We completed an association-mapping study across the 1-LOD-unit-down supporting interval, using two independent white case-control data sets (CATHGEN, initial and validation) to evaluate association under the peak. Single-nucleotide polymorphisms (SNPs) evenly spaced at 100-kb intervals were screened in the initial data set (N=468). Promising SNPs (P<.1) were then examined in the validation data set (N=514). Significant findings (P<.05) in the combined initial and validation data sets were further evaluated in multiple independent data sets, including a family based data set (N=2,954), an African American case-control data set (N=190), and an additional white control data set (N=255). The association between genotype and aortic atherosclerosis was examined in 145 human aortas. The peakwide survey found evidence of association in SNPs from multiple genes. The strongest associations were found in three SNPs from the kalirin (KALRN) gene, especially in patients with early-onset CAD (P=.00001-00028 in the combined CATHGEN data sets). In-depth investigation of the gene found that an intronic SNP, rs9289231, was associated with early-onset CAD in all white data sets examined (P<.05). In the joint analysis of all white early-onset CAD cases (N=332) and controls (N=546), rs9289231 was highly significant (P=.00008), with an odds-ratio estimate of 2.1. Furthermore, the risk allele of this SNP was associated with atherosclerosis burden (P=.03) in 145 human aortas. KALRN is a protein with many functions, including the inhibition of inducible nitric oxide synthase and guanine-exchange-factor activity. KALRN and two other associated genes identified in this study (CDGAP and MYLK) belong to the Rho GTPase-signaling pathway. Our data suggest the importance of the KALRN gene and the Rho GTPase-signaling pathway in the pathogenesis of CAD. PMID- 17357072 TI - A genetic association study of chromosome 11q22-24 in two different samples implicates the FXYD6 gene, encoding phosphohippolin, in susceptibility to schizophrenia. AB - Previous linkage analyses of families with multiple cases of schizophrenia by us and others have confirmed the involvement of the chromosome 11q22-24 region in the etiology of schizophrenia, with LOD scores of 3.4 and 3.1. We now report fine mapping of a susceptibility gene in the 11q22-24 region, determined on the basis of a University College London (UCL) sample of 496 cases and 488 supernormal controls. Confirmation was then performed by the study of an Aberdeen sample consisting of 858 cases and 591 controls (for a total of 2,433 individuals: 1,354 with schizophrenia and 1,079 controls). Seven microsatellite or single-nucleotide polymorphism (SNP) markers localized within or near the FXYD6 gene showed empirically significant allelic associations with schizophrenia in the UCL sample (for D11S1998, P=.021; for rs3168238, P=.009; for TTTC20.2, P=.048; for rs1815774, P=.049; for rs4938445, P=.010; for rs4938446, P=.025; for rs497768, P=.023). Several haplotypes were also found to be associated with schizophrenia; for example, haplotype Hap-F21 comprising markers rs10790212-rs4938445-rs497768 was found to be associated with schizophrenia, by a global permutation test (P=.002). Positive markers in the UCL sample were then genotyped in the Aberdeen sample. Two of these SNPs were found to be associated with schizophrenia in the Scottish sample (for rs4938445, P=.044; for rs497768, P=.037). The Hap-F21 haplotype also showed significant association with schizophrenia in the Aberdeen sample, with the same alleles being associated (P=.013). The FXYD6 gene encodes a protein called "phosphohippolin" that is highly expressed in regions of the brain thought to be involved in schizophrenia. The protein functions by modulating the kinetic properties of Na,K-ATPase to the specific physiological requirements of the tissue. Etiological base-pair changes in FXYD6 or in associated promoter/control regions are likely to cause abnormal function or expression of phosphohippolin and to increase genetic susceptibility to schizophrenia. PMID- 17357073 TI - Genetic analysis of 103 candidate genes for coronary artery disease and associated phenotypes in a founder population reveals a new association between endothelin-1 and high-density lipoprotein cholesterol. AB - Coronary artery disease (CAD) is a major health concern in both developed and developing countries. With a heritability estimated at ~50%, there is a strong rationale to better define the genetic contribution to CAD. This project involves the analysis of 884 individuals from 142 families (with average sibships of 5.7) as well as 558 case and control subjects from the Saguenay Lac St-Jean region of northeastern Quebec, with the use of 1,536 single-nucleotide polymorphisms (SNPs) in 103 candidate genes for CAD. By use of clusters of SNPs to generate multiallelic haplotypes at candidate loci for segregation studies within families, suggestive linkage for high-density lipoprotein (HDL) cholesterol is observed on chromosome 1p36.22. Furthermore, several associations that remain significant after Bonferroni correction are observed with lipoprotein-related traits as well as plasma concentrations of adiponectin. Of note, HDL cholesterol levels are associated with an amino acid substitution (lysine/asparagine) at codon 198 (rs5370) of endothelin-1 (EDN1) in a sex-specific manner, as well as with a SNP (rs2292318) located 7.7 kb upstream of lecithin cholesterol acyl transferase (LCAT). Whereas the other observed associations are described in the current literature, these two are new. Using an independent validation sample of 806 individuals, we confirm the EDN1 association (P<.005), whereas the LCAT association was nonsignificant (P=.12). PMID- 17357074 TI - Leveraging the HapMap correlation structure in association studies. AB - Recent high-throughput genotyping technologies, such as the Affymetrix 500k array and the Illumina HumanHap 550 beadchip, have driven down the costs of association studies and have enabled the measurement of single-nucleotide polymorphism (SNP) allele frequency differences between case and control populations on a genomewide scale. A key aspect in the efficiency of association studies is the notion of "indirect association," where only a subset of SNPs are collected to serve as proxies for the uncollected SNPs, taking advantage of the correlation structure between SNPs. Recently, a new class of methods for indirect association, multimarker methods, has been proposed. Although the multimarker methods are a considerable advancement, current methods do not fully take advantage of the correlation structure between SNPs and their multimarker proxies. In this article, we propose a novel multimarker indirect-association method, WHAP, that is based on a weighted sum of the haplotype frequency differences. In contrast to traditional indirect-association methods, we show analytically that there is a considerable gain in power achieved by our method compared with both single marker and multimarker tests, as well as traditional haplotype-based tests. Our results are supported by empirical evaluation across the HapMap reference panel data sets, and a software implementation for the Affymetrix 500k and Illumina HumanHap 550 chips is available for download. PMID- 17357075 TI - The strength of selection on ultraconserved elements in the human genome. AB - Ultraconserved elements are stretches of consecutive nucleotides that are perfectly conserved in multiple mammalian genomes. Although these sequences are identical in the reference human, mouse, and rat genomes, we identified numerous polymorphisms within these regions in the human population. To determine whether polymorphisms in ultraconserved elements affect fitness, we genotyped unrelated human DNA samples at loci within these sequences. For all single-nucleotide polymorphisms tested in ultraconserved regions, individuals homozygous for derived alleles (alleles that differ from the rodent reference genomes) were present, viable, and healthy. The distribution of allele frequencies in these samples argues against strong, ongoing selection as the force maintaining the conservation of these sequences. We then used two methods to determine the minimum level of selection required to generate these sequences. Despite the lack of fixed differences in these sequences between humans and rodents, the average level of selection on ultraconserved elements is less than that on essential genes. The strength of selection associated with ultraconserved elements suggests that mutations in these regions may have subtle phenotypic consequences that are not easily detected in the laboratory. PMID- 17357076 TI - Association mapping via regularized regression analysis of single-nucleotide polymorphism haplotypes in variable-sized sliding windows. AB - Large-scale haplotype association analysis, especially at the whole-genome level, is still a very challenging task without an optimal solution. In this study, we propose a new approach for haplotype association analysis that is based on a variable-sized sliding-window framework and employs regularized regression analysis to tackle the problem of multiple degrees of freedom in the haplotype test. Our method can handle a large number of haplotypes in association analyses more efficiently and effectively than do currently available approaches. We implement a procedure in which the maximum size of a sliding window is determined by local haplotype diversity and sample size, an attractive feature for large scale haplotype analyses, such as a whole-genome scan, in which linkage disequilibrium patterns are expected to vary widely. We compare the performance of our method with that of three other methods--a test based on a single nucleotide polymorphism, a cladistic analysis of haplotypes, and variable-length Markov chains--with use of both simulated and experimental data. By analyzing data sets simulated under different disease models, we demonstrate that our method consistently outperforms the other three methods, especially when the region under study has high haplotype diversity. Built on the regression analysis framework, our method can incorporate other risk-factor information into haplotype-based association analysis, which is becoming an increasingly necessary step for studying common disorders to which both genetic and environmental risk factors contribute. PMID- 17357077 TI - Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels. AB - Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, we genotyped 1,343 single-nucleotide polymorphisms (SNPs) in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, we found a significant association of interleukin 6 soluble receptor (IL-6 SR) with European ancestry on chromosome 1 (LOD 4.59), in a region that includes the gene for this receptor (IL-6R). Genotyping 19 SNPs showed that the effect is largely explained by an allele at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL-6 SR in a Japanese cohort. We replicate this association (P<<1.0x10-12) and also demonstrate a new association with circulating levels of a different molecule, IL 6 (P<3.4x10-5). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P<<1.0x10-12 for IL-6 SR, and P<2.0x10-9 for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant. PMID- 17357078 TI - Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. AB - The accumulation of mildly deleterious missense mutations in individual human genomes has been proposed to be a genetic basis for complex diseases. The plausibility of this hypothesis depends on quantitative estimates of the prevalence of mildly deleterious de novo mutations and polymorphic variants in humans and on the intensity of selective pressure against them. We combined analysis of mutations causing human Mendelian diseases, of human-chimpanzee divergence, and of systematic data on human genetic variation and found that ~20% of new missense mutations in humans result in a loss of function, whereas ~27% are effectively neutral. Thus, the remaining 53% of new missense mutations have mildly deleterious effects. These mutations give rise to many low-frequency deleterious allelic variants in the human population, as is evident from a new data set of 37 genes sequenced in >1,500 individual human chromosomes. Surprisingly, up to 70% of low-frequency missense alleles are mildly deleterious and are associated with a heterozygous fitness loss in the range 0.001-0.003. Thus, the low allele frequency of an amino acid variant can, by itself, serve as a predictor of its functional significance. Several recent studies have reported a significant excess of rare missense variants in candidate genes or pathways in individuals with extreme values of quantitative phenotypes. These studies would be unlikely to yield results if most rare variants were neutral or if rare variants were not a significant contributor to the genetic component of phenotypic inheritance. Our results provide a justification for these types of candidate-gene (pathway) association studies and imply that mutation-selection balance may be a feasible evolutionary mechanism underlying some common diseases. PMID- 17357079 TI - Assessing the functional characteristics of synonymous and nonsynonymous mutation candidates by use of large DNA constructs. AB - As we identify more and more genetic changes, either through mutation studies or population screens, we need powerful tools to study their potential molecular effects. With these tools, we can begin to understand the contributions of genetic variations to the wide range of human phenotypes. We used our catalogue of molecular changes in patients with carbamyl phosphate synthetase I (CPSI) deficiency to develop such a system for use in eukaryotic cells. We developed the tools and methods for rapidly modifying bacterial artificial chromosomes (BACs) for eukaryotic episomal replication, marker expression, and selection and then applied this protocol to a BAC containing the entire CPSI gene. Although this CPSI BAC construct was suitable for studying nonsynonymous mutations, potential splicing defects, and promoter variations, our focus was on studying potential splicing and RNA-processing defects to validate this system. In this article, we describe the construction of this system and subsequently examine the mechanism of four putative splicing mutations in patients deficient in CPSI. Using this model, we also demonstrate the reversible role of nonsense-mediated decay in all four mutations, using small interfering RNA knockdown of hUPF2. Furthermore, we were able to locate cryptic splicing sites for the two intronic mutations. This BAC-based system permits expression studies in the absence of patient RNA or tissues with relevant gene expression and provides experimental flexibility not available in genomic DNA or plasmid constructs. Our splicing and RNA degradation data demonstrate the advantages of using whole-gene constructs to study the effects of sequence variation on gene expression and function. PMID- 17357080 TI - Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. AB - We have previously reported that an X-linked recessive form of chronic idiopathic intestinal pseudo-obstruction (CIIPX) maps to Xq28. To select candidate genes for the disease, we analyzed the expression in murine fetal brain and intestine of 56 genes from the critical region. We selected and sequenced seven genes and found that one affected male from a large CIIPX-affected kindred bears a 2-bp deletion in exon 2 of the FLNA gene that is present at the heterozygous state in the carrier females of the family. The frameshift mutation is located between two close methionines at the filamin N terminus and is predicted to produce a protein truncated shortly after the first predicted methionine. Loss-of-function FLNA mutations have been associated with X-linked dominant nodular ventricular heterotopia (PVNH), a central nervous system (CNS) migration defect that presents with seizures in females and lethality in males. Notably, the affected male bearing the FLNA deletion had signs of CNS involvement and potentially has PVNH. To understand how the severe frameshift mutation we found can explain the CIIPX phenotype and its X-linked recessive inheritance, we transiently expressed both the wild- type and mutant filamin in cell culture and found that filamin translation can start from either of the two initial methionines in these conditions. Therefore, translation of a normal shorter filamin can occur in vitro from the second methionine downstream of the 2-bp insertion we found. We confirmed this, demonstrating that the filamin protein is present in the patient's lymphoblastoid cell line that shows abnormal cytoskeletal actin organization compared with normal lymphoblasts. We conclude that the filamin N terminal region between the initial two methionines is crucial for proper enteric neuron development. PMID- 17357081 TI - Mitochondrial DNA variation of modern Tuscans supports the near eastern origin of Etruscans. AB - The origin of the Etruscan people has been a source of major controversy for the past 2,500 years, and several hypotheses have been proposed to explain their language and sophisticated culture, including an Aegean/Anatolian origin. To address this issue, we analyzed the mitochondrial DNA (mtDNA) of 322 subjects from three well-defined areas of Tuscany and compared their sequence variation with that of 55 western Eurasian populations. Interpopulation comparisons reveal that the modern population of Murlo, a small town of Etruscan origin, is characterized by an unusually high frequency (17.5%) of Near Eastern mtDNA haplogroups. Each of these haplogroups is represented by different haplotypes, thus dismissing the possibility that the genetic allocation of the Murlo people is due to drift. Other Tuscan populations do not show the same striking feature; however, overall, ~5% of mtDNA haplotypes in Tuscany are shared exclusively between Tuscans and Near Easterners and occupy terminal positions in the phylogeny. These findings support a direct and rather recent genetic input from the Near East--a scenario in agreement with the Lydian origin of Etruscans. Such a genetic contribution has been extensively diluted by admixture, but it appears that there are still locations in Tuscany, such as Murlo, where traces of its arrival are easily detectable. PMID- 17357082 TI - Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms. AB - To date, only the H1 MAPT haplotype has been consistently associated with risk of developing the neurodegenerative disease progressive supranuclear palsy (PSP). We hypothesized that additional genetic loci may be involved in conferring risk of PSP that could be identified through a pooling-based genomewide association study of >500,000 SNPs. Candidate SNPs with large differences in allelic frequency were identified by ranking all SNPs by their probe-intensity difference between cohorts. The MAPT H1 haplotype was strongly detected by this methodology, as was a second major locus on chromosome 11p12-p11 that showed evidence of association at allelic (P<.001), genotypic (P<.001), and haplotypic (P<.001) levels and was narrowed to a single haplotype block containing the DNA damage-binding protein 2 (DDB2) and lysosomal acid phosphatase 2 (ACP2) genes. Since DNA damage and lysosomal dysfunction have been implicated in aging and neurodegenerative processes, both genes are viable candidates for conferring risk of disease. PMID- 17357084 TI - Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice. AB - We report a female patient with a de novo balanced translocation, 46,X,t(X;2)(p11.2;q37)dn, who exhibits seizures, capillary abnormality, developmental delay, infantile hypotonia, and obesity. The 2q37 breakpoint observed in association with the seizure phenotype is of particular interest, because it lies near loci implicated in epilepsy in humans and mice. Fluorescence in situ hybridization mapping of the translocation breakpoints showed that no known genes are disrupted at Xp11.2, whereas diacylglycerol kinase delta (DGKD) is disrupted at 2q37. Expression studies in Drosophila and mouse suggest that DGKD is involved in central nervous system development and function. Electroencephalographic assessment of Dgkd mutant mice revealed abnormal epileptic discharges and electrographic seizures in three of six homozygotes. These findings implicate DGKD disruption by the t(X;2)(p11.2;q37)dn in the observed phenotype and support a more general role for DGKD in the etiology of seizures. PMID- 17357085 TI - Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. AB - Branchio-oto-renal syndrome (BOR) is an autosomal dominant developmental disorder characterized by the association of branchial arch defects, hearing loss, and renal anomalies. Mutations in EYA1 are known to cause BOR. More recently, mutations in SIX1, which interacts with EYA1, were identified as an additional cause of BOR. A second member of the SIX family of proteins, unc-39 (SIX5), has also been reported to directly interact with eya-1 in Caenorhabditis elegans. We hypothesized that this interaction would be conserved in humans and that interactors of EYA1 represent good candidate genes for BOR. We therefore screened a cohort of 95 patients with BOR for mutations in SIX5. Four different heterozygous missense mutations were identified in five individuals. Functional analyses of these mutations demonstrated that two mutations affect EYA1-SIX5 binding and the ability of SIX5 or the EYA1-SIX5 complex to activate gene transcription. We thereby identified heterozygous mutations in SIX5 as a novel cause of BOR. PMID- 17357083 TI - Medical sequencing at the extremes of human body mass. AB - Body weight is a quantitative trait with significant heritability in humans. To identify potential genetic contributors to this phenotype, we resequenced the coding exons and splice junctions of 58 genes in 379 obese and 378 lean individuals. Our 96-Mb survey included 21 genes associated with monogenic forms of obesity in humans or mice, as well as 37 genes that function in body weight related pathways. We found that the monogenic obesity-associated gene group was enriched for rare nonsynonymous variants unique to the obese population compared with the lean population. In addition, computational analysis predicted a greater fraction of deleterious variants within the obese cohort. Together, these data suggest that multiple rare alleles contribute to obesity in the population and provide a medical sequencing-based approach to detect them. PMID- 17357086 TI - Germline mutation of INI1/SMARCB1 in familial schwannomatosis. AB - Patients with schwannomatosis develop multiple schwannomas but no vestibular schwannomas diagnostic of neurofibromatosis type 2. We report an inactivating germline mutation in exon 1 of the tumor-suppressor gene INI1 in a father and daughter who both had schwannomatosis. Inactivation of the wild-type INI1 allele, by a second mutation in exon 5 or by clear loss, was found in two of four investigated schwannomas from these patients. All four schwannomas displayed complete loss of nuclear INI1 protein expression in part of the cells. Although the exact oncogenetic mechanism in these schwannomas remains to be elucidated, our findings suggest that INI1 is the predisposing gene in familial schwannomatosis. PMID- 17357087 TI - Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome. AB - TREX1 constitutes the major 3'-->5' DNA exonuclease activity measured in mammalian cells. Recently, biallelic mutations in TREX1 have been shown to cause Aicardi-Goutieres syndrome at the AGS1 locus. Interestingly, Aicardi-Goutieres syndrome shows overlap with systemic lupus erythematosus at both clinical and pathological levels. Here, we report a heterozygous TREX1 mutation causing familial chilblain lupus. Additionally, we describe a de novo heterozygous mutation, affecting a critical catalytic residue in TREX1, that results in typical Aicardi-Goutieres syndrome. PMID- 17357088 TI - A study of Ki-67, c-erbB2 and cyclin D-1 expression in CIN-I, CIN-III and squamous cell carcinoma of the cervix. AB - The histological criteria for cervical intraepithelial neoplastic lesions and their follow-ups have been established, but their reproducibility, specificity and sensibility are not certain. Immunohistochemical markers provide more information on each specific case, in order to facilitate its classification and, eventually, its prognosis. Using immunohistochemical techniques, this study analyzes the prognostic value of three markers (Ki-67, c-erbB2 and Cyclin D1) in cases of low grade squamous intraepithelial neoplasia (CIN-I), high grade squamous intraepithelial neoplasia (CIN-III), and infiltrating squamous cell carcinoma (SCC) taken from a group of cervical samples. In situ hybridization was performed in order to detect high-risk HPV. High risk HPV was demonstrated in 82%, 89% and 100% of the LGSIL, HGSIL and SCC cases, respectively. C-erbB2 expression was detected in 9%, 33% and 50% of the LSIL, HGSIL and SCC cases, respectively. The Ki-67 LI was 25%, 68% and 65.5% in the LGSIL, HGSIL and SCC cases, respectively. Nuclear Cyclin D1 expression was seen in 82%, 11% and 30% of the CIN-I,CIN-III and SCC cases, respectively. We observed that the cytoplasmic cyclin D1 expression increased with the severity of the lesion instead of the nuclear expression decreasing with the progression of the pathology. Nuclear and cytoplasmic Cyclin D1 expression seemed to be related to HPV high risk infection. We concluded that Cyclin D1, cerbB2 and The Ki-67 LI expression changed in relation to the severity of the lesion and that they could be helpful in making a differential diagnosis. PMID- 17357089 TI - Short-term exposure of mice to gasoline vapor increases the metallothionein expression in the brain, lungs and kidney. AB - Environmental airborne pollution has been repeatedly shown to affect multiple aspects of brain and cardiopulmonary function, leading to cognitive and behavioral changes and to the pronounced inflammatory response in the respiratory airways. Since in the cellular defense system the important role might have stress proteins-metallothionein (MT)-I and MT-II, which are involved in sequestration and dispersal of metal ions, regulation of the biosynthesis and activities of zinc-dependent transcription factors, as well as in cellular protection from reactive oxygen species, genotoxicity and apoptosis, in this study we investigated their expression in the brain, lungs and kidney, following intermittent exposure of mice to gasoline vapor. Control groups consisted of intact mice and of those closed in the metabolic chamber and ventilated with fresh air. The data obtained by immunohistochemistry showed that gasoline inhalation markedly upregulated the MTs expression in tissues which were directly or indirectly exposed to toxic components, significantly increasing the number of MT I+II positive cells in CNS (the entorhinal cortex, ependymal cells, astroglial cells in subventricular zone and inside the brain parenchyma, subgranular and CA1 CA3 zone of the dentate gyrus in hippocampus and macrophages-like cells in perivascular spaces), in the lungs (pneumocytes type I and type II) and in the kidneys (parietal wall of Bowman capsule, proximal and distal tubules). The data point to the protective and growth-regulatory effects of MT I + II on places of injuries, induced by inhalation of gasoline vapor. PMID- 17357090 TI - Ecophysiological responses of the seminal vesicle of Libyan jird (Meriones libycus) to the Saharan conditions: histological, morphometric and immunohistochemical analysis. AB - The Libyan jird (Meriones libycus) is a nocturnal Saharan Rodent submitted to a seasonal cycle of reproduction characterized by a short active period during spring and beginning of summer, and a long phase of sexual quiescence from the end of summer until the end of winter. During this cycle, the male reproductive organs, and more particularly seminal vesicles, experience some important weight and histological variations. During the breeding period, the wall of each seminal vesicle describes several folds radiating inside a broad lumen filled with a very abundant secretion. The wall is limited with high columnar epithelial cells surrounded with extracellular matrix restricted to some connnective fibres located in the narrow axis of the folds and in the chorion. The fibro-muscular wall is narrow. During sexual quiescence, the seminal vesicles regress. No secretion has been observed inside the lumen. The wall of lumen is now surrounded with a single cubic epithelium. The persistent epithelial folds possess a wide axis. The hypertrophied extracellular matrix is constituted with a very tight and abundant connective tissue. The fibro-muscular wall is thick. A quantitative morphometric study was performed with automatic image analysis that allowed to quantify the seasonal variations of the histological components. The numerical values obtained agree with the histological images observed, the epithelial surface area (microm2) is high in spring and significantly weak during sexual quiescence. The stroma and the fibro-muscular wall occupy an important surface area on sections during the resting period compared with the value collected during the active phase. The study of the apoptosis by TUNEL method revealed the presence of a considerable number of apoptotic nuclei in the epithelial fraction during the resting phase. The indirect immunohistochemical method allowed us to visualize the presence of types I and III collagen in the extracellular matrix, weak during the period of breeding, intense and diffuse during the resting season like in castrated Meriones libycus. PMID- 17357091 TI - Autometallographic tracing of quantum dots. AB - A short clarifying view of how semiconductor quantum dots (QDs) can be made visible in tissue sections by autometallographic (AMG) silver enhancement and how the introduction of AMG enhanceable gold nanoparticles into isolated cells can be used to follow the fate of these marked cells in organisms and cell cultures. As the AMG approach for visualizing quantum dots is extremely sensitive, QDs less than one nanometer can be made visible at both LM and EM levels. PMID- 17357092 TI - Epithelial apoptosis in mechanistically distinct methods of injury in the murine small intestine. AB - Gut epithelial apoptosis is involved in the pathophysiology of multiple diseases. This study characterized intestinal apoptosis in three mechanistically distinct injuries with different kinetics of cell death. FVB/N mice were subjected to gamma radiation, Pseudomonas aeruginosa pneumonia or injection of monoclonal anti CD3 antibody and sacrificed 4, 12, or 24 hours post-injury (n=10/time point). Apoptosis was quantified in the jejunum by hematoxylin and eosin (H&E), active caspase-3, terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling (TUNEL), in situ oligoligation reaction (ISOL,) cytokeratin 18, and annexin V staining. Reproducible results were obtained only for H&E, active caspase-3, TUNEL and ISOL, which were quantified and compared against each other for each injury at each time point. Kinetics of injury were different with early apoptosis highest following radiation, late apoptosis highest following anti CD3, and more consistent levels following pneumonia. ISOL was the most consistent stain and was always statistically indistinguishable from at least 2 stains. In contrast, active caspase-3 demonstrated lower levels of apoptosis, while the TUNEL assay had higher levels of apoptosis in the most severely injured intestine regardless of mechanism of injury. H&E was a statistical outlier more commonly than any other stain. This suggests that regardless of mechanism or kinetics of injury, ISOL correlates to other quantification methods of detecting gut epithelial apoptosis more than any other method studied and compares favorably to other commonly accepted techniques of quantifying apoptosis in a large intestinal cross sectional by balancing sensitivity and specificity across a range of times and levels of death. PMID- 17357093 TI - Histological and histochemical evaluation of human oral mucosa constructs developed by tissue engineering. AB - Reconstruction of large oral mucosa defects is often challenging, since the shortage of healthy oral mucosa to replace the excised tissues is very common. In this context, tissue engineering techniques may provide a source of autologous tissues available for transplant in these patients. In this work, we developed a new model of artificial oral mucosa generated by tissue engineering using a fibrin-agarose scaffold. For that purpose, we generated primary cultures of human oral mucosa fibroblasts and keratinocytes from small biopsies of normal oral mucosa using enzymatic treatments. Then we determined the viability of the cultured cells by electron probe quantitative X-ray microanalysis, and we demonstrated that most of the cells in the primary cultures were alive and had high K/Na ratios. Once cell viability was determined, we used the cultured fibroblasts and keratinocytes to develop an artificial oral mucosa construct by using a fibrin-agarose extracellular matrix and a sequential culture technique using porous culture inserts. Histological analysis of the artificial tissues showed high similarities with normal oral mucosa controls. The epithelium of the oral substitutes had several layers, with desmosomes and apical microvilli and microplicae. Both the controls and the oral mucosa substitutes showed high suprabasal expression of cytokeratin 13 and low expression of cytokeratin 10. All these results suggest that our model of oral mucosa using fibrin-agarose scaffolds show several similarities with native human oral mucosa. PMID- 17357094 TI - Down regulation of gastric and intestinal phenotypic expression in Epstein-Barr virus-associated stomach cancers. AB - AIMS: We have previously demonstrated the importance of gastric and intestinal phenotypic expression for stomach carcinogenesis. In this study, we focused on Epstein-Barr virus (EBV)-associated stomach cancers, with special attention to Cdx2. METHODS AND RESULTS: We evaluated the expression of gastric and intestinal phenotypic markers by immunohistochemistry in 35 EBV-positive [EBV (+)] and 75 EBV-negative [EBV (-)] stomach cancers in Colombia. The lesions were divided phenotypically into gastric (G), gastric-and-intestinal mixed (GI), intestinal (I), and null (N) phenotypes. In the EBV (+) cases, the lesions were divided phenotypically into 9 G (25.7%), 1 GI (2.9%), 3 I (8.6%), and 22 N (62.9%) types. Similarly, the EBV (-) lesions were also classified phenotypically as 15 G (20.0%), 19 GI (25.3%), 24 I (32.0%), and 17 N (22.7%) types. The proportion of N type EBV (+) lesions was higher than for their EBV (-) counterparts (P<0.0001). The expression of Cdx2 and MUC2 was also found to be significantly lower in EBV (+) than in EBV (-) stomach cancers (P=0.0001; P<0.0001). Cdx2 expression in the intestinal metaplastic glands present in non-neoplastic mucosa surrounding EBV (+) lesions was also significantly lower than in EBV (-) tumors (P=0.016) despite no evidence of EBV infection. CONCLUSIONS: EBV (+) stomach cancers are characterized by low expression of intestinal phenotype markers, including Cdx2, and only occasional gastric phenotypic expression. PMID- 17357095 TI - Protein-energy malnutrition alters histological and ultrastructural characteristics of the bone marrow and decreases haematopoiesis in adult mice. AB - Protein-energy malnutrition (PEM) decreases resistance to infection by impairing a number of physiological processes, including haematopoiesis. The aim of this study was to evaluate the microanatomical aspects of bone marrow (BM) in mice that were subjected to PEM, in particular, with respect to the components of the local extracellular matrix and the proliferative activity of haematopoietic cells. For this, histological, histochemical, immunohistochemical and ultrastructural techniques were used. Two-month old male Swiss mice were fed with a low-protein diet containing 4% protein and control mice fed a 20% protein diet. When the experimental group had attained a 25% loss of their original body weight, we collected the different biological samples. Malnourished mice had presented severe BM atrophy as well as a reduction in proliferating cell nuclear antigen and gelatinous degeneration. The malnourished mice had more fibronectin accretion in paratrabecular and endosteal regions and more laminin deposition in perisinusal sites than controls. Endosteal cell activation and hyperplasia were found, suggesting their participation in the process. Additionally, we have observed a decrease in the capacity of malnourished haematopoietic stroma to support the growth of haematopoietic stem cells (CD34+) in vitro. These findings point to a structural impairment of the haematopoietic microenvironments in mice with PEM, possibly hampering the interactions between cells and cellular signalling. PMID- 17357097 TI - Therapeutic neovascularization for peripheral arterial diseases: advances and perspectives. AB - Recently, with the better understanding of the mechanisms of neovascularization, many new therapeutic approaches to enhance neovascularization have emerged. Of these diverse emerging methods, use of growth factors and cells are the two major ones. This review will provide an update on the present understanding of the basic mechanisms of angiogenesis, vasculogenesis, and arteriogenesis, as a basis for designing future pro-neovascularization treatments. Several angiogenic factors including vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) have been implicated in augmenting the neovascularization process. However, single growth factors are not sufficient to generate functional vessels. In synergistic or complementary manner, these factors may be used in harmony to form long-term functional vessels. Cell therapy has the potential to supply stem/progenitor cells and multiple angiogenic factors to the region of ischemia. However, the efficacy of stem cells transplantation may be impaired by low survival rate, insufficient cell number and impaired function in aging and diseases. Combination of cells or cells primed with growth factor(s) or genetic modification may augment the therapeutic efficacy. This paper reviews critical literature in depth to elucidate the mechanism of therapeutic neovascularization, angiogenic factor therapy and cell transplantation. Based on past experience and actual knowledge, we propose future strategies for clinical application and discuss the problems and controversies that need to be addressed in order to fully exploit the potential of growth factors and/or cell transplantation with clinical relevance. PMID- 17357098 TI - Immune based therapies in cancer. AB - Immunotherapy of cancer has become a more promising approach in the past decade. Developments in both basic immunology and tumor biology have increased our knowledge of the interactions between the tumor cells and the immune system. The molecular identification of tumor-associated antigens and understanding of immunological pathways have cleared the way for development of different strategies for anti-tumor vaccines. The success of any cancer vaccine relies on the induction of an effective tumor-specific immune response to break tolerance and to elicit a long lasting anti-tumor immunity. It is also increasingly clear that the interactions of host-tumor are quite complicated leading to tumor escape mechanisms, which add another level of difficulty to this interaction. This review will summarize the recent developments in tumor immunotherapy as well as the clinical trials addressing novel immunotherapeutic approaches to cancer. PMID- 17357096 TI - Histological complexities of pancreatic lesions from transgenic mouse models are consistent with biological and morphological heterogeneity of human pancreatic cancer. AB - Although pancreatic cancer is the fourth leading cause of cancer death, it has received much less attention compared to other malignancies. There are several transgenic animal models available for studies of pancreatic carcinogenesis, but most of them do not recapitulate, histologically, human pancreatic cancer. Here we review some detailed molecular complexity of human pancreatic cancer and their reflection in histomorphological complexities of pancreatic lesions developed in various transgenic mouse models with a special concern for studying the effects of chemotherapeutic and chemopreventive agents. These studies usually require a large number of animals that are at the same age and gender and should be either homozygote or heterozygote but not a mixture of both. Only single-transgene models can meet these special requirements, but many currently available models require a mouse to simultaneously bear several transgene alleles. Thus it is imperative to identify new gene promoters or enhancers that are specific for the ductal cells of the pancreas and are highly active in vivo so as to establish new single-transgene models that yield pancreatic ductal adenocarcinomas for chemotherapeutic and chemopreventive studies. PMID- 17357099 TI - Alternate approach to understanding the molecular mechanisms of stroke-induced injury. AB - Research in the area of stroke has not yielded any new treatments, besides tissue plasminogen activator. New findings are suggesting that the therapeutic window of providing neuroprotection is wider than once thought. Moreover, the role of the peripheral immune system in abetting neurodegeneration is being elucidated, but it appears this reaction occurs 2-3 days after the stroke. This mini-review examines this new evidence about the molecular mechanisms leading to stroke induced neuronal death, which suggests new therapeutic approaches to its treatment. PMID- 17357103 TI - Development of a T1 contrast agent for magnetic resonance imaging using MnO nanoparticles. PMID- 17357104 TI - Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells. AB - A crucial event for the induction of an anti-viral immune response is the coordinated, phenotype-dependent migration of dendritic cells (DC) to sites of infection and secondary lymphoid organs. Here we show that the vaccinia virus (VV) strains Western Reserve (WR) and modified virus Ankara (MVA) inhibit directional migration of mature DC toward the lymphoid chemokines CCL19 and CXCL12 without affecting surface expression of the respective chemokine receptors or impairing undirected cellular locomotion. Instead, infection with VV results in a deficiency of extracellular signal-regulated kinase-1 and a disturbance of intracellular calcium mobilization, indicating a viral interference with signaling events downstream of the surface chemokine receptors. In immature DC, apart from inhibiting chemokine-induced migration of infected DC, infection with both VV strains increases expression of the inflammatory chemokine receptors CCR1 and CXCR1 on non-infected bystander DC, which depends on the activity of IFN alpha. Although functional, these chemokine receptors are resistant to lipopolysaccharide-induced down-regulation. In addition, VV-infected and non infected bystander DC fail to up-regulate the lymphoid chemokine receptor CCR7 upon activation, together pointing to a disability to undergo the chemokine receptor switch. This study shows that VV targets directional migration of professional antigen-presenting cells at multiple functional levels, revealing a potent viral strategy of immune escape. PMID- 17357105 TI - No essential role for tripeptidyl peptidase II for the processing of LCMV-derived T cell epitopes. AB - The proteasome is critically involved in the production of MHC class I-restricted T cell epitopes. Approximately 20% of all peptides generated by the proteasome are too large for direct presentation by MHC class I molecules. Reits et al. (Immunity 2004. 20: 495-506) suggested that a major portion of proteasomal products are larger than 15 amino acids and require further degradation by the tripeptidyl peptidase II (TPPII) before becoming ligands of MHC class I molecules. Using the well-characterized lymphocytic choriomeningitis virus (LCMV) model, the role of TPPII in the processing of several LCMV-derived T cell epitopes was investigated. In contrast to Reits' proposal, TPPII inhibition and TPPII overexpression experiments revealed that five out of six LCMV-derived CD8(+) T cell epitopes were not affected by inhibition of TPPII, while one epitope (GP276) was slightly reduced upon TPPII overexpression. Additionally, we demonstrated that the processing of two epitopes derived from ovalbumin and murine cytomegalovirus were not altered by TPPII inhibition. We propose that TPPII is not generally required for the production of MHC class I peptides, but the presentation of some peptides can be negatively affected by TPPII. PMID- 17357106 TI - GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development. AB - The transcription factor GATA3 is essential at multiple stages of T cell development, including the earliest double-negative stages, beta-selection and CD4 single-positive thymocytes. Here, we show that in CD2-GATA3 transgenic mice, with enforced GATA3 expression driven by the CD2 promoter, thymocytes have reduced levels of CD5, which is a negative regulator of TCR signaling participating in TCR repertoire fine-tuning. Reduction of CD5 expression was most prominent in CD4(+)CD8(+) double-positive (DP) cells and was associated with increased levels of the transcription factor E2A. Conversely, GATA3-deficient DP thymocytes showed consistently higher CD5 levels and defective TCR up-regulation during their development towards the CD4(lo)CD8(lo) subpopulation. CD2-GATA3 transgenic mice carrying the MHC class II-restricted TCR DO11.10 also manifested decreased CD5 levels. As in these TCR-transgenic mice reduced CD5 expression cannot result from an effect of GATA3 on repertoire selection, we conclude that enforced GATA3 interferes with the developmentally regulated increase of CD5 levels. Enforced GATA3 expression in DO11.10 transgenic mice was also accompanied by enhanced TCR expression during CD4 positive selection. Because GATA3 is induced by TCR signaling in DP thymocytes, our findings indicate that GATA3 establishes a positive feedback loop that increases TCR surface expression in developing CD4 lineage cells. PMID- 17357107 TI - The impact of HLA-B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV. AB - The factors controlling epitope selection in the T cell response to persistent viruses are not fully understood, and we have examined this issue in the context of four HLA-B*35-binding peptides from the pp65 antigen of human cytomegalovirus, two of which are previously undescribed. Striking differences in the hierarchy of immunodominance between these four epitopes were observed in healthy virus carriers expressing HLA-B*3501 versus B*3508, two HLA-B allotypes that differ by a single amino acid at position 156 (HLA-B*3501, (156)Leucine; HLA-B*3508, (156)Arginine) that projects from the alpha2 helix into the centre of the peptide binding groove. While HLA-B*3501(+) individuals responded most strongly to the (123)IPSINVHHY(131) and (366)HPTFTSQY(373) epitopes, HLA-B*3508(+) individuals responded preferentially to (103)CPSQEPMSIYVY(114) and (188)FPTKDVAL(195). By comparing peptide-MHC association and disassociation rates with peptide immunogenicity, it was clear that dissociation rates correlate more closely with the hierarchy of immunodominance among the four pp65 peptides. These findings demonstrate that MHC micropolymorphism at positions outside the primary anchor residue binding pockets can have a major impact on determinant selection in antiviral T cell responses. Such influences may provide the evolutionary pressure that maintains closely related MHC molecules in diverse human populations. PMID- 17357108 TI - BAFF and LPS cooperate to induce B cells to become susceptible to CD95/Fas mediated cell death. AB - Microorganisms with pathogen-associated molecular patterns (PAMP) activate B cells directly by binding to TLR and also indirectly by inducing APC to release cytokines such as BAFF that promote B cell survival. We found that murine B cells activated concomitantly with LPS (TLR-4 ligand) and BAFF are protected from spontaneous apoptosis, but are more susceptible to Fas/CD95-mediated cell death. This increased susceptibility to Fas-induced apoptosis is associated with a dramatic coordinated up-regulation of Fas/CD95 and IRF-4 expression through a mechanism mediated, at least in part, by inhibition of the MEK/ERK pathway. Up regulation of Fas/CD95 by BAFF is restricted to B cells activated through TLR-4, but not through TLR-9, BCR or CD40. TLR ligands differ in the BAFF family receptors (R) they induce on B cells: BAFF-R is increased by the TLR4 ligand, LPS, but not by the TLR9 ligand, CpG-containing oligodeoxynucleotides, which, in contrast, strongly up-regulates transmembrane activator and CAML interactor (TACI). This suggests the up-regulation of Fas by BAFF is mediated by BAFF-R and not by TACI. Consistently, APRIL, which binds to TACI and B cell maturation antigen but not BAFF-R, did not enhance Fas expression on LPS-activated B cells. Increased susceptibility to Fas-mediated killing of B cells activated with LPS and BAFF may be a fail-safe mechanism to avoid overexpansion of nonspecific or autoreactive B cells. PMID- 17357109 TI - 70-kDa heat shock proteins: specific interactions with HLA-DR molecules and their peptide fragments. AB - Heat shock protein 70 (HSP70):peptide complexes are involved in MHC class I and class II-restricted antigen presentation enabling enhanced activation of antigen specific T cells. Here, we investigated the potential of bacterial and mammalian HSP70 molecules to interact with peptide fragments from HLA-DR and the corresponding complete HLA-DR molecules. Peptide fragments were found to interact with DnaK, the HSP70 homologue from E. coli, but less with stress-inducible human Hsp70. Only a peptide sequence exclusively found in rheumatoid arthritis protective HLA-DR molecules did not interact with DnaK. Subsequently, we investigated the interaction of complete HLA-DR molecules with HSP70 and detected a specific HSP70:HLA-DR interaction, with highest affinity for human stress inducible Hsp70. In contrast to the peptide fragments, no allele-specific differences in Hsp70 affinity were detected with complete HLA-DR molecules. Interaction with HLA-DR molecules was increased at lowered pH values, whereas HSP70-chaperoned peptides were released at acidic pH, thus HSP70 could serve as scanner and carrier for antigenic peptides of self or foreign origin and transfer chaperoned peptides onto MHC class II molecules in acidic late endosomal compartments. Our findings indicate that direct interaction between mammalian HSP70 and HLA-DR molecules could be involved in the HSP70-mediated enhancement of MHC class II-restricted peptide presentation and CD4(+) T cell activation. PMID- 17357110 TI - Expression of a non-DNA-binding Ikaros isoform exclusively in B cells leads to autoimmunity but not leukemogenesis. AB - Ikaros is a transcriptional regulator whose function is essential for B cell development. It is expressed in the hematopoietic stem cell (HSC) through the mature B cell stage. Using genetically engineered mice in which the endogenous Ikaros gene is disrupted, it has been shown that a lack of Ikaros leads to a block in B cell development and that its severe diminution results in a hyperresponsive B cell compartment. Ikaros expression within the HSC has led to speculation as to whether the role of Ikaros in B cell biology is largely accomplished prior to B cell specification. In addition, widespread expression of Ikaros in hematopoietic cells leads to the possibility that some or all of the observed defects are not B cell autonomous. In this report, we demonstrate that over-expression of a dominant interfering Ikaros isoform exclusively in B cells has profound effects on mature B cell function. We provide evidence that continued high-level expression of Ikaros is essential for homeostasis of peripheral lymphocytes and maintenance of B cell tolerance. We also show that deregulation of Ikaros activity does not rapidly result in B cell leukemogenesis as it does with 100% penetrance within the T cell lineage. PMID- 17357113 TI - Quantitative assessment of regional left ventricular function with cardiac MRI: three-dimensional centersurface method. AB - OBJECTIVES: The purpose of this study was to provide the first in vivo validation of a three-dimensional (3D) method to quantify regional left ventricular (LV) function with cardiac magnetic resonance (CMR) imaging after myocardial infarction (MI). BACKGROUND: Current cardiac methods to analyze LV function are limited by geometric assumptions and observer biases. METHODS: MI was induced percutaneously by 90-min proximal left circumflex artery balloon occlusion in 25 Yucatan minipigs. Cine and contrast-enhanced (CE) CMR imaging was performed at 5 days (n = 21) and 8 weeks (n = 22) post-MI. Twelve control animals without MI were also imaged. Regional wall thickening was measured orthogonal to the myocardial wall using the centersurface method. The left ventricle was divided into 16 segments (six basal 60 degrees , six middle 60 degrees , four apical 90 degrees ). Normal ranges for segmental wall thickness and wall thickening were defined as mean +/- 2D in control hearts. Hypokinesis was defined as a segmental thickening value below the normal range. RESULTS: Hypokinesis following MI was identified in the inferior, inferolateral and anterolateral segments when compared with controls and corresponded to areas of infarction by CE CMR. The aggregate wall thickening was also expressed as a percentage at 5 days (Infarct zone: 15% +/- 16% vs. NonInfarct zone 33% +/- 20%, P < 0.001) and 8 weeks (Infarct zone 20% +/- 20% vs. NonInfarct zone 32% +/- 22%, P < 0.001). CONCLUSIONS: The centersurface method can quantify regional wall thickening and spatially identify regions of abnormal function in 3D after MI without relying on geometric assumptions. This method may be a valuable tool to quantify regional LV function in the assessment of myocardial viability, ischemia, infarction, and the response to therapeutic interventions. PMID- 17357114 TI - Test-retest reliability of an instrumented speculum for measuring vaginal closure force. AB - AIMS: The study aimed to: a) determine reliability of an instrumented speculum designed for measuring intravaginal closure pressure, and b) compare findings with a comparable device reported in the literature. The goal of these new devices is to reduce subjectivity, improve precision, and acknowledge reliability issues in quantifying levator ani closure force acting on the vagina. METHODS: The instrumented speculum consisted of two parallel aluminum bills, similar in size to a Peterson speculum. Strain gages located near the root of each bill measure the magnitude of force exerted in the distal vagina. A contraction of the "U-shaped" levator ani muscle closes the levator hiatus with resultant reaction force measured by the speculum in the mid-sagittal plane. We tested the device in twelve nulliparous women making repeated measures within and across 3 different visit days. All measures were made by the same investigator. RESULTS: Same day measures were repeatable within +/-3.8 N by the third visit, with lesser repeatability on the 1st and 2nd visit days. Across days, repeatability was improved by Visits 2 and 3 with a coefficient of repeatability between those days of +/-5.5 N. Better repeatability was obtained using averaged scores rather than 'best effort' ; but average scores can underestimate best effort. CONCLUSION: Reasonable within-visit repeatability was found. Across-visit repeatability is consistent with the known difficulty that women have in maximally isolating and activating their levator ani muscles. The results corroborate the repeatability results of Dumoulin et al. [2004] using a similar type of dynamometer. PMID- 17357115 TI - Overactive bladder in diabetes: a peripheral or central mechanism? AB - AIMS: To study diabetic cystopathy with reference to overactive bladder (OAB). METHODS: We retrospectively analyzed diabetic cystopathy in our digitized database that comprised 2300 case records, including data from a lower urinary tract symptoms questionnaire, data from a urodynamic study, and data from neurological examinations. RESULTS: Diabetic cystopathy was seen in 4% of cases (84 cases): 58 males, 26 females; mean age, 60.8 years; duration of diabetes, 143.5 months; HbA1C, 7.7 %. In addition to large post-void residual and decreased sensation, OAB, detrusor overactivity (DO), and increased bladder sensation were seen in 55%, 42%, and 14%, respectively. The frequency of DO in patients with increased bladder sensation was 58%. DO increased with age, but not with the duration of diabetes. A brain MRI was performed in 32 cases. The frequency of multiple cerebral infarction (MCI) in patients with DO was 76.5%. The remaining 23.5% of patients with DO had no MCI, and the remaining 42% with increased bladder sensation had no DO. CONCLUSIONS: OAB commonly occurs in diabetic cystopathy. Both central and peripheral mechanisms are involved, e.g., MCI due to diabetic cerebral vasculopathy for the DO, and, to a lesser extent, peripheral nerve irritation for the DO and increased bladder sensation. PMID- 17357116 TI - Gastroschisis and associated defects: an international study. AB - Our objective was to evaluate the frequency and type of malformations associated with gastroschisis in a large pool of international data, to identify malformation patterns, and to evaluate the role of maternal age in non-isolated cases. Case-by-case information from 24 registries, all members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), were evaluated. After the exclusion of other abdominal wall defects cases were classified as: (a) isolated; (b) recognizable syndrome, chromosomal or not; (c) multiple congenital anomalies (MCA). Our results showed that out of 3,322 total cases 469 non-isolated cases were registered (14.1%): 41 chromosomal syndromes, 24 other syndromes, and 404 MCA. Among MCA four groups of anomalies were most frequent: CNS (4.5%), cardio-vascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). No similar patterns emerged except two patterns resembling limb-body wall complex and OEIS. In both of them the gastroschisis could be however misclassified. Chromosomal trisomies and possibly non-syndromic MCA are associated with an older maternal age more than isolated cases. On consideration of our data and the most valid studies published in the literature, the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%, with a few cases associated to recognizable syndromes. Recognized syndromes with gastroschisis seem to be so exceptional that the well documented and validated cases are worth being published as interesting case report. An appropriate case definition in etiological studies should include only isolated gastroschisis after an appropriate definition of isolated and non isolated cases and a thorough case-by-case review. PMID- 17357117 TI - Personal digital assistant (PDA) cell phone units produce elevated extremely-low frequency electromagnetic field emissions. AB - Initial tests indicate that personal and occupational use of personal digital assistants (PDAs or palm-held wireless units) produce high intensity bursts of extremely-low frequency electromagnetic fields (ELF-EMF). These emissions could result in comparatively high ELF-EMF exposure in persons that carry a PDA close to the body (i.e., in a pocket or on a belt); or held to the head for cell phone conversations. ELF-EMF emissions of 10 microT were recorded on PDAs during normal office use over a 24 h test period. Results of ELF-EMF measurements show that email transmit and receive functions produce rapid, short-duration ELF-EMF spikes in the 2-10 microT range, each lasting several seconds to over a minute apparently depending on file download size. Some units produced spikes as high as 30-60 microT during email activities. Cell phone activity on PDAs produced continuously elevated ELF-EMF readings in the 0.5-1 microT range, as opposed to the rapid spiking pattern for email receipt and transmission. Switching the PDA unit from "OFF" to "ON" position resulted in single ELF-EMF pulses of over 90 microT on two units. Email downloads into the PDA can occur randomly throughout the day and night when the unit is "ON"; thus the user who wears the PDA may be receiving high-intensity ELF-EMF pulses throughout the day and night. The frequency of email traffic on the PDA, and the power switching unit (battery unit) may affect the frequency and intensity of ELF-EMF emissions. PMID- 17357119 TI - Synthesis of enantiomerically pure isotopomers of 2-phenylpropionic acids. AB - A series of enantiomerically pure [D,(13)C]-labeled isotopomeric 2 phenylpropionic acids were efficiently synthesized using a diastereoselective alkylation and kinetic resolution strategy. PMID- 17357118 TI - GC-MS detection of chiral markers in cocoa beans of different quality and geographic origin. AB - Fermented cocoa beans (Theobroma cacao L., Sterculiaceae) from different countries of origin (Ecuador, Ghana, Trinidad) and cocoa beans roasted under defined conditions (industrial roasting; 150-220 degrees C for 20 min, dry roasting in conventional oven) were analyzed for their contents of certain chiral hydroxy acids, catechins, and amino acids. Cocoa beans are fermented, dried, and industrially transformed by roasting for the production of chocolate, cocoa powders, and other cocoa-related products. Fermentation and roasting conditions influence the contents of chiral compounds such as hydroxy acids, amino acids, and polyphenols, depending on technological procedures as well as some technical parameters. The aim of this work was to check if the content and nature of the named chiral compounds present both in fermented and roasted cocoa beans could be related to the traditional parameters used to classify the variety of seeds and the degree of fermentation. The extent of racemization of amino acids in fermented cocoa beans was low while it slowly increased during roasting, depending on the temperature applied. L-lactic acid was always higher than the D form while citric acid was generally the most abundant hydroxy acid detected in beans. A correlation was found between polyphenol content and degree of fermentation, while epimerization of (-)-epicatechin to (+)-catechin was observed during roasting. On the whole, results showed that several chiral compounds could be considered as good quality markers for cocoa seeds and cocoa-related products of different quality and geographic origin. PMID- 17357120 TI - Parallel kinetic resolution of an oxazolidinone using a quasi-enantiomeric combination of [D,13C]-isotopomers of pentafluorophenyl 2-phenyl propionate. AB - Parallel kinetic resolution of Evans' phenylglycine derived oxazolidinone using an equimolar combination of quasi-enantiomeric active esters (derived from [D,13C]-labeled 2-phenylpropionic acid) was achieved. The levels of stereocontrol were high, leading to products with predictable configurations. PMID- 17357121 TI - Mutual kinetic separation of isotopomers of pentafluorophenyl 2-phenyl propionate using quasi-enantiomeric oxazolidinones. AB - Mutual separation of an equimolar mixture of quasi-enantiomeric [D,13C]-labeled isotopomers of pentafluorophenyl 2-phenylpropionate can be achieved efficiently by use of two quasi-enantiomeric Evans' oxazolidinones. The levels of stereocontrol were high, leading to products with predictable configurations. PMID- 17357122 TI - Monitoring transplanted human mesenchymal stem cells in rat and rabbit bladders using molecular magnetic resonance imaging. AB - AIMS: This study investigated whether superparamagnetic iron oxide (SPIO)-labeled human mesenchymal stem cells (hMSCs) may be monitored non-invasively by in vivo magnetic resonance (MR) imaging with conventional 1.5-T system examinations in the bladders of rats and rabbits. METHODS: SPIO were transferred to hMSCs, using GenePORTER. After SPIO-labeled hMSCs were transplanted into the animal bladders, serial T2-weighted MR images and histological examinations were performed over a 4-week period. RESULTS: hMSCs loaded with SPIO, compared to unlabeled cells, showed similar viability. SPIO-labeled hMSCs underwent normal chondrogenic, adipogenic, and osteogenic differentiation. For SPIO-labeled hMSCs concentrations that were greater than 1x10(5), in vitro MR images showed a decrease in signal intensity. MR signal intensity at the areas of SPIO-labeled hMSCs in rat and rabbit bladders were decreased and confined locally. After injection of SPIO labeled hMSCs into the bladder, MR imaging demonstrated that hMSCs could be seen for at least 12 weeks post-injection. The presence of iron was confirmed with Prussian blue staining in histological sections. CONCLUSIONS: Our findings suggest that hMSCs in animal bladders can be monitored non-invasively with conventional MR imaging. PMID- 17357123 TI - Psychogenic urinary dysfunction: a uro-neurological assessment. AB - AIMS: The diagnosis of psychogenic urinary dysfunction (PUD) is one of exclusion, particularly from urologic and neurologic causes, and is usually accompanied by more obvious psychologic/ psychiatric features. We here describe patients with PUD who were diagnosed in our uro- neurological laboratory. MATERIALS AND METHODS: We reviewed the digitized records of 2,300 urodynamic cases treated in the past 6 years to identify patients who fulfilled the diagnostic criteria of PUD. All 2,300 patients had completed a urinary questionnaire and undergone both electromyography (EMG)-cystometry and a detailed neurological examination. In addition, pressure-flow analysis, neurophysiology tests including sphincter EMG analysis, and MRI of the brain and spinal cord were performed as applicable. RESULTS: PUD was seen in 16 cases (0.7%): 6 men, 10 women, mean age 37 years. Lower urinary tract symptoms (LUTS) included overactive bladder (OAB) alone in 5, difficult urination alone in one, and both in 10. LUTS commonly occurred in particular situations, for example, OAB only while riding the train. Some patients showed extremely infrequent toileting. The urodynamic findings were normal except for increased bladder sensation (50%) for OAB and acontractile detrusor (31%) for difficulty. The final diagnosis was conversion reaction in six followed by anxiety in four. CONCLUSIONS: PUD patients experienced the situational occurrence of OAB and/or difficult urination and, in some patients, extremely infrequent toileting. The main urodynamic abnormalities were increased bladder sensation and acontractile detrusor. However, even in cases suggestive of PUD, a non-PUD pathology behind the symptoms should be explored. PMID- 17357124 TI - Mutations in GJB2, GJB6, and mitochondrial DNA are rare in African American and Caribbean Hispanic individuals with hearing impairment. AB - Autosomal recessive nonsyndromic sensorineural hearing impairment (ARNSHI) comprises 80% of familial hearing loss cases. Approximately half result from mutations in the connexin 26 (Cx26) gene, GJB2, in Caucasian populations. Heterozygous mutations in GJB2 occasionally co-occur with a deletion of part of GJB6 (connexin 30; Cx30). It is estimated that approximately 1% of deafness is maternally inherited, due to mutations in mitochondrial DNA (mtDNA). Few studies have focused on the frequency of mutations in connexins or mtDNA in African American (AA) and Caribbean Hispanic (CH) admixture populations. In this study, we performed bidirectional sequencing of the GJB2 gene and polymerase chain reaction (PCR) screening for the common GJB6 deletion, as well as PCR/RFLP analysis for three mutations in mtDNA (A1555G, A3243G, A7445G), in 109 predominantly simplex AA and CH individuals. Variations found were a 101T > C (M34T; 1/101 cases), 109G > A (V37I; 1/101), 35delG (mutation; 4/101, (3/4) of non-AA/CH ethnicity), 167delT (mutation; 1/101), 139G > T (mutation; E47X; 1/101 homozygote, consanguineous), -15C > T (1/101), 79G > A (V27I; 9/101), 380G > A (R127H; 4/101; Guyana, India, Pakistan ethnicity), 670A > C (Indeterminate; K224Q; 1/101), 503A > G (novel; K168R; 3/101) and 684C > A (novel; 1/101). All but one of the AA and CH patients had monoallelic variations. There were no hemizygous GJB6 deletions in those with monoallelic GJB2 variations. We also did not identify any patients with the three mutations in mtDNA. Bidirectional sequencing of the GJB2 gene was performed in 187 AA and Hispanic healthy individuals. Our results reveal that GJB2 mutations, GJB6 deletions, and mtDNA mutations may not be significant in these minority admixture populations. PMID- 17357125 TI - Genetic drift. Reconnected by sign. PMID- 17357126 TI - Clinical and imaging evidence of zolpidem effect in hypoxic encephalopathy. AB - We conducted a randomized, double-blind, placebo-controlled, single-patient (N = 1) trial to evaluate the efficacy of zolpidem in a 48-year-old woman with an akinetic mutism. Motor and cognitive examinations and functional imaging were performed. Acute administration of zolpidem markedly improved motor performance and neuropsychological status. Cerebral metabolism ((18)F-fluorodeoxyglucose positron emission tomography) increased in postrolandic territories and in frontal cortex. Using the H(2) (15)O positron emission tomography, we found a drug-induced activation in the anterior cingulate and orbitofrontal cortices. Zolpidem induced a transient improvement in motor and cognitive performances. This paradoxical effect could result from an activation of limbic loops modulating motivational processes. PMID- 17357127 TI - Estrogen-induced cholestasis results in a dramatic increase of b-series gangliosides in the rat liver. AB - Hepatic ganglioside composition was investigated in normal and cholestatic Wistar rats. Cholestasis was induced by 17alpha-ethinylestradiol (EE; 5 mg/kg body weight s.c. for 18 days). As compared with controls, the EE administration resulted in severe cholestasis, as indicated by biochemical as well as morphological signs. Gangliosides isolated from the liver tissue were separated by TLC, with resorcinol-HCl detection and densitometric evaluation. As compared with controls, the total hepatic lipid sialic acid content in cholestatic rats was increased almost 2-fold (44.3 +/- 15.2 vs 79.1 +/- 9.0 nmol/g wet weight of liver tissue, p < 0.01). This increase was primarily due to the increase of ganglioside GD1a (3.6 +/- 1.0 vs 11.8 +/- 3.0 nmol/g wet weight of liver tissue, p = 0.001), as well as to the enormous up-regulation of b-series gangliosides GD3 (0.08 +/- 0.03 vs 2.0 +/- 1.2 nmol/g wet weight of liver tissue, p = 0.002), GD1b (0.1 +/- 0.06 vs 5.4 +/- 1.6 nmol/g wet weight of liver tissue, p = 0.002) and GT1b (0.06 +/- 0.03 vs 6.4 +/- 2.6 nmol/g wet weight of liver tissue, p = 0.002). As the majority of gangliosides are concentrated in cell membranes, our findings suggest that dramatic increase of b-series gangliosides might contribute to the protection of hepatocytes against the deleterious effects of cholestasis. PMID- 17357128 TI - The 2006 Human Genome Variation Society scientific meeting. AB - The annual scientific meeting of the Human Genome Variation Society (HGVS) was held on the 9th of October, 2006, in New Orleans, Louisiana. This year's annual meeting had two main themes, "Tools to Evaluate Pathogenicity" and "The Human Variome Project." The ability to determine if a DNA variant affects the phenotype is important if we wish to understand the genetic contribution to disease. Genetic variants are continually being identified in research and molecular diagnostic laboratories, but functional tests are not always available. Attempts are now being made to create software that will help us determine if a variation will affect either the function of the protein, the expression of the gene, or the stability and processing of the mRNA. For the second theme, there is an interest in creating a database that brings together genetic variation with phenotypic variation in individuals. The Human Variome Project was created to begin this process. Now that the human genome sequence is all but completed, the next phase of the human genome era will be to associate genetic variation with its effect on the phenotype and differing disease states. At this scientific meeting there were also several papers focusing on the identification, classification, and functional effects of variation. These talks are representative of the questions, problems, and solutions that are being considered by researchers involved in the study of variation in the human genome. PMID- 17357129 TI - Sweating in Parkinsonian patients with wearing-off. AB - Disorders of the autonomic nervous system are common in Parkinson's disease (PD). Earlier studies suggest that some nonmotor symptoms may fluctuate with the motor symptoms, but the possible interrelationship between motor phenomena and sweating has not been studied. The authors measured sweating by using an evaporimeter on three different areas of the body (right hand, left hand, chest) immediately before the morning PD medication (baseline), and thereafter hourly up to 4 hour, in 16 PD patients with wearing-off type of motor fluctuations and in 15 patients without clinical motor fluctuations. The clinical state of the patients was evaluated using the Unified Parkinson's Disease Rating Scale motor score every hour. Sweating increased during the 4-hour follow-up, and reached its maximum level at the time of the highest Unified Parkinson's Disease Rating Scale motor score phase (off-stage) in patients with wearing-off (initially affected hand, P = 0.007; left hand, P = 0.004; right hand, P = 0.034), but in the patients without wearing-off no changes in sweating were observed during the follow-up. Sweating of the left hand (P < 0.001), right hand (P < 0.001), and initially affected hand (P = 0.008) during the whole observation period was significantly higher in patients with motor fluctuations than in those without. The present study shows that sweating fluctuates in conjunction with wearing-off phenomenon. PMID- 17357130 TI - Neurological deficits are associated with increased brain calcinosis, hypoperfusion, and hypometabolism in idiopathic basal ganglia calcification. AB - We report two familial cases of idiopathic basal ganglia calcification. A 60-year old proband with choreoathetosis, dysarthria, and cognitive decline showed more extensive brain calcinosis, hypoperfusion, and hypometabolism than did his asymptomatic 82-year-old mother. The mother had no frontal lobe calcinosis but basal ganglia and dentate nucleus depositions were detectable. Perfusion neuroimaging, however, was normal in the asymptomatic mother and abnormal in the clinically impaired proband. The presence of calcinosis cannot be used as an index of neurological impairment but the extent of calcinosis and reduction in perfusion and metabolism may be useful for separating symptomatic from asymptomatic subjects with IBGC. These findings suggest that an interruption of neuronal circuitry may cause neurological deficits. The degree of neurological deficits may correlate with the severity of calcinosis and the reduction of perfusion and metabolism. PMID- 17357131 TI - Radicular and nonradicular back pain in Parkinson's disease: a controlled study. AB - Postural abnormalities and increased muscle tone in Parkinson's disease (PD) may cause back pain. In this controlled study, we analyzed features of back pain in PD patients. The prevalence of back pain was 74% in PD patients (n = 101) when compared with 27% in control patients (n = 132; P < 0.0001, fisher's exact test), but did not correlate with disease severity or duration. The mean back pain intensity (visual analog scale of 0-10) was 4.3 for PD patients, and 1.3 for controls. Both radicular and nonradicular types of back pain were more frequent, and back pain caused more impairment in PD patients. However, it is noteworthy that the PD patients in our study did not receive more pain medication than control patients. This suggests that back pain in PD patients is often neglected and insufficiently treated. Our results argue for the routine evaluation of back pain in every patient suffering from PD. PMID- 17357132 TI - Clinical and genetic characterizations of 16q-linked autosomal dominant spinocerebellar ataxia (AD-SCA) and frequency analysis of AD-SCA in the Japanese population. AB - Autosomal dominant spinocerebellar ataxias (AD-SCAs) form a clinically and genetically heterogeneous group of neurodegenerative disorders. Recently, a single nucleotide substitution in the 5'-untranslated region of the puratrophin-1 gene was found to be associated with one type of AD-SCA linked to chromosome 16q (16q-SCA). To obtain further insight into the contribution of the C-to-T substitution in the puratrophin-1 gene to the clinical and genetic characteristics of patients with 16q-SCA, we analyzed 686 families with 719 individuals diagnosed with progressive ataxia. We found C-to-T substitution in the puratrophin-1 gene in 57 unrelated families with 65 affected individuals. The mean age at onset in the patients with 16q-SCA was 59.1 (range, 46-77). Ataxia is the most common initial symptom. The elderly patients over 65 occasionally showed other accompanying clinical features including abnormalities in tendon reflexes, involuntary movements, and reduced vibration sense. We also examined the frequency of the AD-SCA subtype, considering the effects of age at onset. In the 686 AD-SCA families, SCA6 and Machado-Joseph disease/SCA3 are frequent subtypes, followed by dentatorubral-pallidoluysian atrophy and 16q-SCA. 16q-SCA is not a rare subtype of Japanese AD-SCA, particularly in patients with ages at onset over 60. PMID- 17357133 TI - Ciprofloxacin-induced palatal tremor. AB - We describe an 84-year-old man with an unusual clinical presentation of palatal tremor in association with ciprofloxacin treatment. The patient had rhythmical movements not only of the soft palate but also of the face and trunk. Complete resolution of the symptoms occurred 2 days after discontinuation of ciprofloxacin and administration of sodium valproate. This is the first reported case of palatal tremor secondary to the use of ciprofloxacin. PMID- 17357134 TI - Decreased myocardial (123)I-MIBG uptake and impaired facial expression recognition in a patient with REM sleep behavior disorder. PMID- 17357135 TI - Video documented follow-up of liver transplantation in Wilson's disease with predominant neurological manifestation. AB - Wilson's disease (WD) is a rare autosomal-recessive disorder of copper metabolism with predominantly hepatic and extrapyramidal motor symptoms. Copper chelating therapy has proven to be an effective treatment for WD. Yet, if conservative treatment fails, liver transplantation (LT) often is the only remaining therapeutic option. The indication for LT especially in patients with stable liver function but severe neurological manifestation is debated controversially. In this case report, we document the follow up of neurological symptoms in WD after LT for the first time on video. PMID- 17357136 TI - Ultrastructure of the protonephridia of larval Rugiloricus cf. cauliculus, male Armorloricus elegans, and female Nanaloricus mysticus (Loricifera). AB - The protonephridial system of several Loricifera was studied by transmission electron microscopy. A larval specimen of Rugiloricus cf. cauliculus possesses two protonephridia, which are "capped" frontally by a compact mass of still undifferentiated gonadal cells. Each protonephridium consists of four monociliary terminal cells and four canal cells with a diplosome but no cilia. Because of incomplete series of sections and unsatisfactory fixation, the outleading cell(s) could not be detected. In a male specimen of Armorloricus elegans, each gonad contains two protonephridia that open into the gonadal lumen. Each protonephridium consists of two monociliary terminal cells, each forming a filter, two nonciliated canal cells, and two nephroporus cells. The protonephridial lumina of the latter cells fuse to one common lumen, which unites with the gonadal lumen. Preliminary observations on the protonephridia of a female Nanaloricus mysticus reveal a more complicated arrangement of interdigitating terminal and canal cells. One or two terminal cells form their own individual filter or four cells form a common compound filter. The cilium of the terminal cells of all species investigated are surrounded by a palisade of nine microvilli that support the filter barrier made of an extracellular matrix. An additional filter diaphragm could be traced between the pores in the cell wall of each terminal cell of A. elegans. The urogenital system of the Loricifera differs from that of the Priapulida in that the protonephridia of the former are completely integrated into the gonad, whereas the excretory organs of the latter open into the urogenital duct caudally of the gonads. PMID- 17357138 TI - Uterine epithelial changes during placentation in the viviparous skink Eulamprus tympanum. AB - We used scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to describe the complete ontogeny of simple placentation and the development of both the yolk sac placentae and chorioallantoic placentae from nonreproductive through postparturition phases in the maternal uterine epithelium of the Australian skink, Eulamprus tympanum. We chose E. tympanum, a species with a simple, noninvasive placenta, and which we know, has little net nutrient uptake during gestation to develop hypotheses about placental function and to identify any difference between the oviparous and viviparous conditions. Placental differentiation into the chorioallantoic placenta and yolk sac placenta occurs from embryonic Stage 29; both placentae are simple structures without specialized features for materno/fetal connection. The uterine epithelial cells are not squamous as previously described by Claire Weekes, but are columnar, becoming increasingly attenuated because of the pressure of the impinging underlying capillaries as gestation progresses. When the females are nonreproductive, the luminal uterine surface is flat and the microvillous cells that contain electron dense vesicles partly obscure the ciliated cells. As vitellogenesis progresses, the microvillous cells are less hypertrophied than in nonreproductive females. After ovulation and fertilization, there is no regional differentiation of the uterine epithelium around the circumference of the egg. The first differentiation, associated with the chorioallantoic placentae and yolk sac placentae, occurs at embryonic Stage 29 and continues through to Stage 39. As gestation proceeds, the uterine chorioallantoic placenta forms ridges, the microvillous cells become less hypertrophied, ciliated cells are less abundant, the underlying blood vessels increase in size, and the gland openings at the uterine surface are more apparent. In contrast, the yolk sac placenta has no particular folding with cells having a random orientation and where the microvillous cells remain hypertrophied throughout gestation. However, the ciliated cells become less abundant as gestation proceeds, as also seen in the chorioallantoic placenta. Secretory vesicles are visible in the uterine lumen. All placental differentiation and cell detail is lost at Stage 40, and the uterine structure has returned to the nonreproductive condition within 2 weeks. Circulating progesterone concentrations begin to rise during late vitellogenesis, peak at embryonic Stages 28-30, and decline after Stage 35 in the later stages of gestation. The coincidence between the time of oviposition and placental differentiation demonstrates a similarity during gestation in the uterus between oviparous and simple placental viviparous squamates. PMID- 17357139 TI - Physical activity and risk of endometrial cancer: the European prospective investigation into cancer and nutrition. AB - The etiologic role of physical activity in endometrial cancer risk remains unclear given the few epidemiologic studies that have been conducted. To investigate this relation more fully, an analysis was undertaken in the European prospective investigation into cancer and nutrition (EPIC). During an average 6.6 years of follow-up, 689 incident endometrial cancer cases were identified from an analytic cohort within EPIC of 253,023 women. Cox proportional hazards models were used to estimate the associations between type of activity (total, occupational, household, recreational) and endometrial cancer risk. For total activity, women in the highest compared with the lowest quartile of activity had a risk of 0.88 (95% confidence interval (95% CI=0.61-1.27). No clear associations between each type of activity and endometrial cancer risk were found for the total study population combined. Associations were more evident in the stratified results, with premenopausal women who were active versus inactive experiencing a risk of 0.66 (95% CI=0.38-1.14) overall. Among premenopausal women, for household and recreational activities the risk estimates in the highest as compared with the lowest quartiles were, respectively, 0.48 (95% CI=0.23-0.99) and 0.78 (95% CI=0.44-1.39). No effect modification by body mass index, hormone replacement therapy, oral contraceptive use or energy intake was found. This study provides no evidence of a protective effect of increased physical activity in endometrial cancer risk in all women but some support for a benefit among premenopausal women. The relative risk reductions are most apparent for household activities. PMID- 17357140 TI - Shunt responsive progressive supranuclear palsy? PMID- 17357141 TI - Self-reported adherence versus pill count in Parkinson's disease: the NET-PD experience. AB - PURPOSE: To compare the Morisky medication adherence questionnaire to pill counts as measures of adherence in the NET-PD futility clinical trials. BACKGROUND: Like in other chronic diseases, non-adherence with medications occurs in Parkinson's disease (PD), although nonadherence has not been of significant concern in most PD clinical trials. The most common approach to assessment is to do a pill count at each visit. The simple, 4-question Morisky medication adherence questionnaire may provide an alternative approach to monitoring treatment adherence in PD. METHODS: Adherence data from two NET-PD Phase II clinical trials enrolling a total of 413 participants were analyzed. The association between demographic and clinical characteristics and adherence was explored. RESULTS: Ninety-percent of participants took 80% or more of the study drug. However, the Morisky medication adherence questionnaires showed 56% report high and 44% report medium adherence. Agreement between the two measures is fair (ICC = 0.40). CONCLUSIONS: Overall adherence as assessed by pill count appears high. The Morisky medication adherence questionnaire may be useful in PD clinical trials, since it is moderately correlated to pill count and may be more sensitive to nonadherence. PMID- 17357142 TI - Levodopa response in Parkinsonism with multiple mitochondrial DNA deletions. AB - We report a patient with an autosomal dominant chronic progressive external ophthalmoplegia phenotype associated with multiple mtDNA deletions in muscle from a family in which linkage analysis excluded mutations in DNA polymerase gamma (POLG), adenine nucleotide translocase (ANT-1) or C10orf2 (Twinkle). She presented with prominent Parkinsonism characterized by prolonged benefit from levodopa (L-dopa) and the later development of L-dopa induced dyskinesias and motor fluctuations. Thus L-dopa responsiveness, L-dopa induced dyskinesias and motor fluctuations may also occur in atypical Parkinsonism of mitochondrial disease, just as they may in multiple system atrophy. PMID- 17357143 TI - Olfactory loss may be a first sign of idiopathic Parkinson's disease. AB - Recent studies support the idea of olfactory dysfunction as a very early sign of idiopathic Parkinson's disease (IPD). Aim of the present study was to clinically follow-up patients with idiopathic hyposmia to find out the percentage of patients developing IPD after 4 years time. At baseline, olfactory tests had been combined with transcranial sonography of the substantia nigra and (123)I-FP-CIT SPECT imaging. At the present neurological examination, 7% of the individuals with idiopathic hyposmia had developed clinical IPD. Altogether, 13% presented with abnormalities of the motor system. Our data suggest that a combination of olfactory testing and other tests may constitute a screening tool for the risk to develop IPD. PMID- 17357144 TI - The entity of young onset primary cervical dystonia. AB - Primary cervical dystonia is typically an adult onset condition with symptom onset usually in the fifth and sixth decade. Young onset (<28 years) is uncommon. We report 76 patients with cervical dystonia as a presenting or predominant feature, with disease onset before the age of 28. Male to female ratio was 1.24:1 and the mean onset age was 21 (3-28) years. A family history of tremor and/or dystonia was noted in 26.3%. Depression and anxiety attacks were present in 23.7%. Prior injury or surgery involving the neck was noted in 17.1%. 23 (30.3%) experienced spontaneous partial or complete remissions within the first 5 years of onset, but all relapsed. Cervical dystonia was predominantly rotational torticollis. 30% developed extra-nuchal dystonia and tremor affecting contiguous parts but in only one there was spread to affect the legs. All 15 patients tested for the DYT1 gene were negative. 74% responded favorably to botulinum toxin injections, whereas none of the 13 patients treated with L-Dopa preparations had a beneficial response. The distinctive features of this entity are discussed. PMID- 17357145 TI - Increase in GSK3beta gene copy number variation in bipolar disorder. AB - The analysis of submicroscopic copy number variations (CNVs), also known as copy number polymorphisms (CNPs), is emerging as a new tool for understanding the genetic basis of cancer, developmental disorders, and complex traits. One area where this may be particularly useful is in the identification of genetic variants underlying schizophrenia (SZ) and bipolar disorder (BD). Linkage analysis and pharmacological studies carried out over the past decade have implicated a number of positional and physiological candidate genes. Yet, despite extensive analysis, the underlying allelic variants responsible for disease susceptibility have remained, largely, elusive. Although the borders of most CNV have not been precisely mapped, it appears that a considerable number of SZ and BD candidate genes have their coding elements disrupted by polymorphic CNVs, suggesting that these would be good variants to consider for underlying disease susceptibility. One such gene is GSK3beta, which codes for glycogen synthase kinase, a key component of the Wnt signaling pathway and a target of lithium salts. A CNV in the GSK3beta locus at chromosome 3q13.3 appears to disrupt the gene's 3'-coding elements. The CNV also affects two other annotated genes. We now report that patients with BD have an increased frequency of this CNV-primarily the duplication variant-compared with controls (P = 0.002). The finding suggests that GSK3beta may be involved in BD susceptibility in some individuals and that CNVs in this and other candidate genes for psychiatric disorders should be analyzed as causative functional genetic variants. PMID- 17357146 TI - SNP fine mapping of chromosome 8q24 in bipolar disorder. AB - We previously reported linkage to chromosome 8q24 in bipolar disorder (BP) with a LOD of 3.32. We fine mapped the locus with SNPs and tested for association with BP in families with evidence of linkage to the region. We genotyped 249 informative SNPs over 3.4 Mb in an initial sample of 155 nuclear families (352 affected offsprings), and followed up the best findings by genotyping six of the most significantly associated SNPs in a replication sample of 103 nuclear families (231 affected offsprings). We used FBAT and GIST for association tests. Two clusters of SNPs emerged with the strongest evidence of association. The first consisted of three SNPs, approximately 3 kb 5' from the gene ST3GAL1. These SNPs were associated with BP in the initial sample by FBAT (best P = 0.001) and GIST (best P = 0.05) and associated in the replication sample by FBAT (best P = 0.04). The second cluster consisted of four SNPs (one of which was not genotyped in the replication sample), approximately 480 kb 5' of ST3GAL1 in a relative gene desert. These SNPs were associated with BP in the initial sample by FBAT (best P = 0.007) and GIST (best P = 0.03), and marginally associated in the replication sample by FBAT (best P = 0.07) and GIST (P = 0.04). ST3GAL1 belongs to a family of glycosyltransferase proteins, several members of which are highly expressed in the brain and involved in neurogenesis. Several other interesting candidate genes are also located nearby. The congruence of findings across methods and samples suggests further investigation is warranted in these two targeted regions. PMID- 17357147 TI - Meta-analysis of COMT val158met in panic disorder: ethnic heterogeneity and gender specificity. AB - There is strong evidence for a genetic contribution to the pathogenesis of panic disorder, with the functional catechol-O-methyltransferase (COMT) val158met polymorphism having been suggested as a potential susceptibility factor. In the present study, a meta-analysis of six available case-control studies (557 patients with panic disorder and 763 healthy controls in total) on the role of the COMT val158met polymorphism in panic disorder was conducted in an attempt to reconcile previous conflicting results and to facilitate evaluation of the role of COMT gene variation in panic disorder. Overall, no significant association, but strong between-study heterogeneity, was discerned. Analysis of studies pooled by ancestry yielded a significant association of the COMT 158val allele with panic disorder in Caucasian samples and, conversely, a trend towards association of the COMT 158met allele with the disorder in Asian samples. Interestingly, stratification for gender as well as ethnicity revealed that association of the 158val allele in Caucasians and, reciprocally, the 158met allele in Asian samples was restricted to females. The present meta-analysis provides tentative support for the COMT val158met polymorphism as a possible risk factor for panic disorder, with differential effects in Caucasian and Asian populations, and suggests a female-specific effect. However, given the relatively small number of case control studies presently available, several more association studies, preferably including a larger number of family-based studies, are warranted for conclusive evaluation of the COMT val158met polymorphism as a vulnerability factor in panic disorder. PMID- 17357148 TI - Association between cytochrome P450 (CYP) 2C19 polymorphisms and harm avoidance in Japanese. AB - Polymorphic enzyme cytochrome P450 (CYP) 2C19 is expressed not only in the liver but also in the brain and mediates the biotransformation of 5-hydroxytriptamine (5-HT). We investigated possible association between genetic polymorphism of CYP2C19 and individual personality traits, possibly influenced by neurotransmitters. Mentally and physically healthy Japanese subjects were enrolled in this study (n = 352). Temperament and Character Inventory (TCI) and CYP2C19 genotyping were performed in all subjects. We detected CYP2C19*2 and *3 (http://www.imm.ki.se/CYPalleles/) using Amplichip CYP450 DNA tip. The number of genotypes classified as homozygous extensive metabolizer (EM), heterozygous EM, and poor metabolizer were 113, 181, and 58, respectively. Significant difference was found in TCI score in harm avoidance (HA; F = 3.138, P < 0.05). Post hoc analysis showed that TCI score in harm avoidance in homozygous EM was significantly lower than that in heterozygous EM (P < 0.05) or PM (P < 0.05). In sub-item analyses, HA3 (shyness with strangers, P < 0.01) and HA1 (anticipatory worry, P < 0.05) of TCI scores were significantly different among CYP2C19 genotypes. Meanwhile, there were no differences in TCI scores of novelty seeking (NS; F = 0.350, n.s.), reward dependence (RD; F = 1.080, n.s.), or persistence (P; F = 0.786, n.s.) among CYP2C19 genotypes. This study demonstrated that a significant association between CYP2C19 activity and HA is present in Japanese. PMID- 17357149 TI - p75(NTR) gene and suicide attempts in young adults with a history of childhood onset mood disorder. AB - Recently, evidence has accumulated for the role of neurotrophic processes in mood disorders. Neurotrophins operate on receptors, one of which is the p75 neurotrophin receptor (p75(NTR)). We examined three p75(NTR) markers at the p75(NTR) gene, including a missense polymorphism that changes serine to leucine (S205L), for association with suicide attempt (SA) in 203 childhood-onset mood disorder (COMD) cases. There was no difference between COMD suicide attempters and COMD non-attempters with logistic regression models for any of the three markers. We also compared the three polymorphisms between 192 COMD cases and 192 matched healthy controls and found no significant differences between COMD and healthy controls. Our results do not support an association of the p75(NTR) S205L polymorphism with risk for COMD or SA in COMD. PMID- 17357150 TI - ATP-induced chemotaxis of microglial processes requires P2Y receptor-activated initiation of outward potassium currents. AB - Microglial cells are the resident macrophages that are involved in brain injuries and infections. Recent studies using transcranial two-photon microscopy have shown that ATP and P2Y receptors mediated rapid chemotactic responses of miroglia to local injury. However, the molecular mechanism for microglial chemotaxis toward ATP is still unknown. To address this question, we employed a combination of simultaneous perforated whole-cell recordings and time-lapse confocal imaging in GFP-labeled microglia in acute brain slices from adult mice. We found that ATP induced rapid chemotaxis is correlated with P2Y receptor associated-outward potassium current in microglia. Activation of both P2Y receptor and its associated potassium channels are required for ATP-induced chemotaxis and baseline motility of microglial cells. The chemotaxis required the activation of phosphoinositide 3-kinase but not mitogen-activated protein kinase pathway. Our results provide strong evidence that P2Y receptor-associated outward potassium channels and the phosphoinositide 3-kinase pathway are important for ATP-induced microglial motility in acute brain slices. PMID- 17357151 TI - Inhibition of glutamine transport into mitochondria protects astrocytes from ammonia toxicity. AB - Hepatic encephalopathy (HE) is a major neurological complication that occurs in the setting of severe liver failure. Ammonia is a key neurotoxin implicated in this condition, and astrocytes are the principal neural cells histopathologically and functionally affected. Although the mechanism by which ammonia causes astrocyte dysfunction is incompletely understood, glutamine, a by-product of ammonia metabolism, has been strongly implicated in many of the deleterious effects of ammonia on astrocytes. Inhibiting mitochondrial glutamine hydrolysis in astrocytes mitigates many of the toxic effects of ammonia, suggesting the involvement of mitochondrial glutamine metabolism in the mechanism of ammonia neurotoxicity. To determine whether mitochondriaare indeed the organelle where glutamine exerts its toxic effects, we examined the effect of L-histidine, an inhibitor of mitochondrial glutamine transport, on ammonia-mediated astrocyte defects. Treatment of cultured astrocytes with L-histidine completely blocked or significantly attenuated ammonia-induced reactive oxygen species production, cell swelling, mitochondrial permeability transition, and loss of ATP. These findings implicate mitochondrial glutamine transport in the mechanism of ammonia neurotoxicity. PMID- 17357152 TI - Apolipoprotein E deficiency enhances the antigen-presenting capacity of Schwann cells. AB - Apolipoprotein E (apoE) has immunomodulatory properties and has been implicated in the pathogenic mechanism of autoimmune diseases. Previously, the authors found that apoE deficiency increased the susceptibility to experimental autoimmune neuritis (EAN), an animal model for human Guillain-Barre syndrome. To further elucidate the mechanism behind apoE deficiency exacerbating EAN, the authors investigated the role of major target and important antigen-presenting cells of the peripheral nerve system, Schwann cells (SCs), in apoE knockout mice. Treatment of apoE deficient SCs with recombinant mouse interferon-gamma and lipopolysaccharide resulted in higher MHC-II and CD40 expression as compared with normal SCs derived from wild-type mice. The increased MHC-II and CD40 expression on SCs was accompanied by lower levels of intracellular IL-6 production within SCs of apoE deficiency, which is confirmed by the neutralization with anti IL-6 antibody. The increased antigen-presenting capacity of apoE deficient SCs was further explored by enhancement of T cell proliferation co-cultured with P0 peptide 180-199 specific T cells derived from EAN mice immunized with the P0 peptide. In conclusion, apoE may protect mice from EAN and probably also from chronic inflammatory demyelinating polyneuropathy by affecting the antigen presenting function of SCs via influence of IL-6 production. PMID- 17357153 TI - Crystal structure of an archaeal homologue of multidrug resistance repressor protein, EmrR, from hyperthermophilic archaea Sulfolobus tokodaii strain 7. AB - MarR family proteins, MarR, MexR, and EmrR, are known as bacterial regulators for a phenotype resistant to multiple antibiotic drugs. Genomic data have indicated the presence of bacterial-type transcriptional regulators, including MarR family proteins in archaea, though the archaeal transcription system is close to that of eukaryote. To elucidate the structural basis of the transcriptional regulation mechanism of archaeal MarR family proteins, the crystal structure of the ST1710 protein, which was identified as an archaeal EmrR homologue, StEmrR, from hyperthermophilic archaeon Sulfolobus tokodaii strain 7 was determined at 1.45-A resolution. The protein was composed of two N- and C-terminal dimerization domains, and the DNA-binding domain consisted of a winged helix motif, as in the case of bacterial MarR family proteins. Despite the relatively low overall structural similarity between StEmrR and bacterial MarR family proteins, the structure of the DNA-binding domain displayed high structural similarity. A comparison with the crystal structures of bacterial MarR family proteins revealed that structural variation was mainly due to the different orientation of the two helices at the N- and C-termini. Our results indicated that the distance between the two DNA-binding domains of MarR family proteins would be changed by the rotation of the two terminal helices to interact with the target DNA. PMID- 17357154 TI - Crystal structure of recombinant human stromal cell-derived factor-1alpha. PMID- 17357156 TI - Crystal structure of Helicobacter pylori spermidine synthase: a Rossmann-like fold with a distinct active site. AB - Spermidine synthase (putrescine aminopropyltransferase, PAPT) catalyzes the transfer of the aminopropyl group from decarboxylated S-adenosylmethionine to putrescine during spermidine biosynthesis. Helicobacter pylori PAPT (HpPAPT) has a low sequence identity with other PAPTs and lacks the signature sequence found in other PAPTs. The crystal structure of HpPAPT, determined by multiwavelength anomalous dispersion, revealed an N-terminal beta-stranded domain and a C terminal Rossmann-like domain. Structural comparison with other PAPTs showed that HpPAPT has a unique binding pocket between two domains, numerous non-conserved residues, a less acidic electrostatic surface potential, and a large buried space within the structure. HpPAPT lacks the gatekeeping loop that facilitates substrate binding in other PAPTs. PAPTs are essential for bacterial cell viability; thus, HpPAPT may be a potential antimicrobial drug target for H. pylori owing to its characteristic PAPT sequence and distinct conformation. PMID- 17357155 TI - Homology modeling and molecular dynamics simulations of the glycine receptor ligand binding domain. AB - We present a homology based model of the ligand binding domain (LBD) of the homopentameric alpha1 glycine receptor (GlyR). The model is based on multiple sequence alignment with other members of the nicotinicoid ligand gated ion channel superfamily and two homologous acetylcholine binding proteins (AChBP) from the freshwater (Lymnaea stagnalis) and saltwater (Aplysia californica) snails with known high resolution structure. Using two template proteins with known structure to model three dimensional structure of a target protein is especially advantageous for sequences with low homology as in the case presented in this paper. The final model was cross-validated by critical evaluation of experimental and published mutagenesis, functional and other biochemical studies. In addition, a complex structure with strychnine antagonist in the putative binding site is proposed based on docking simulation using Autodock program. Molecular dynamics (MD) simulations with simulated annealing protocol are reported on the proposed LBD of GlyR, which is stable in 5 ns simulation in water, as well as for a deformed LBD structure modeled on the corresponding domain determined in low-resolution cryomicroscopy structure of the alpha subunit of the full-length acetylcholine receptor (AChR). Our simulations demonstrate that the beta-sandwich central core of the protein monomer is fairly rigid in the simulations and resistant to deformations in water. PMID- 17357157 TI - A comparative infrared spectroscopic study of glycoside hydrolases from extremophilic archaea revealed different molecular mechanisms of adaptation to high temperatures. AB - The identification of the determinants of protein thermal stabilization is often pursued by comparing enzymes from hyperthermophiles with their mesophilic counterparts while direct structural comparisons among proteins and enzymes from hyperthermophiles are rather uncommon. Here, oligomeric beta-glycosidases from the hyperthermophilic archaea Sulfolobus solfataricus (Ss beta-gly), Thermosphaera aggregans (Ta beta-gly), and Pyrococcus furiosus (Pf beta-gly), have been compared. Studies of FTIR spectroscopy and kinetics of thermal inactivation showed that the three enzymes had similar secondary structure composition, but Ss beta-gly and Ta beta-gly (temperatures of melting 98.1 and 98.4 degrees C, respectively) were less stable than Pf beta-gly, which maintained its secondary structure even at 99.5 degrees C. The thermal denaturation of Pf beta-gly, followed in the presence of SDS, suggested that this enzyme is stabilized by hydrophobic interactions. A detailed inspection of the 3D structures of these enzymes supported the experimental results: Ss beta-gly and Ta beta-gly are stabilized by a combination of ion-pairs networks and intrasubunit S-S bridges while the increased stability of Pf beta-gly resides in a more compact protein core. The different strategies of protein stabilization give experimental support to recent theories on thermophilic adaptation and suggest that different stabilization strategies could have been adopted among archaea. PMID- 17357158 TI - Predicting protein domain interactions from coevolution of conserved regions. AB - The knowledge of protein and domain interactions provide crucial insights into their function within a cell. Several computational methods have been proposed to detect interactions between proteins and their constitutive domains. In this work, we focus on approaches based on correlated evolution (coevolution) of sequences of interacting proteins. In this type of approach, often referred to as the mirrortree method, a high correlation of evolutionary histories of two proteins is used as an indicator to predict protein interactions. Recently, it has been observed that subtracting the underlying speciation process by separating coevolution due to common speciation divergence from that due to common function of interacting pairs greatly improves the predictive power of the mirrortree approach. In this article, we investigate possible improvements and limitations of this method. In particular, we demonstrate that the performance of the mirrortree method that can be further improved by restricting the coevolution analysis to the relatively conserved regions in the protein domain sequences (disregarding highly divergent regions). We provide a theoretical validation of our results leading to new insights into the interplay between coevolution and speciation of interacting proteins. PMID- 17357159 TI - Exploring the conformational space of protein loops using a mean field technique with MOLS sampling. AB - We have recently developed a computational technique that uses mutually orthogonal Latin square sampling to explore the conformational space of oligopeptides in an exhaustive manner. In this article, we report its use to analyze the conformational spaces of 120 protein loop sequences in proteins, culled from the PDB, having the length ranging from 5 to 10 residues. The force field used did not have any information regarding the sequences or structures that flanked the loop. The results of the analyses show that the native structure of the loop, as found in the PDB falls at one of the low energy points in the conformational landscape of the sequences. Thus, a large portion of the structural determinants of the loop may be considered intrinsic to the sequence, regardless of either adjacent sequences or structures, or the interactions that the atoms of the loop make with other residues in the protein or in neighboring proteins. PMID- 17357160 TI - Human DEAD-box ATPase DDX3 shows a relaxed nucleoside substrate specificity. AB - Human DDX3 (hDDX3) is a DEAD-box protein shown to possess RNA-unwinding and adenosine triphosphatase (ATPase) activities. The hDDX3 protein has been implicated in nuclear mRNA export, cell growth control, and cancer progression. In addition, a role of this protein in the replication of human immunodeficiency virus Type 1 and in the pathogenesis of hepatitis C virus has been recently proposed. Its enzymological properties, however, are largely unknown. In this work, we characterized its ATPase activity. We show that hDDX3 ATPase activity is stimulated by various ribo- and deoxynucleic acids. Comparative analysis with different nucleoside triphosphate analogs showed that the hDDX3 ATPase couples high catalytic efficiency to a rather relaxed substrate specificity, both in terms of base selection and sugar selection. In addition, its ability to recognize the L-stereoisomers of both 3' deoxy- and 2',3' dideoxy-ribose, points to a relaxed stereoselectivity. On the basis of these results, we hypothesize the presence of structural determinants on both the base and the sugar moieties, critical for nucleoside binding to the enzyme. Our results expand the knowledge about the DEAD-box RNA helicases in general and can be used for rational design of selective inhibitors of hDDX3, to be tested as potential antitumor and antiviral agents. PMID- 17357161 TI - Assay for rapid analysis of the tri-peptidase activity of LTA4 hydrolase. AB - Leukotriene A4 hydrolase is a bifunctional zinc metalloenzyme with an epoxide hydrolase activity as well as an arginyl tri-peptidase activity. Detailed enzymological and mechanistic investigations of the latter activity have been hampered by the lack of a rapid and convenient enzyme assay. Here we have developed a new method allowing direct spectrophotometric assessment of the tri peptide cleaving activity of leukotriene A4 hydrolase, as well as other peptidases. The method utilizes two competing substrates, one chromogenic reference substrate together with the tri-peptide substrate of interest, and relies on computer-assisted analysis of progress curves. The chromogenic reference substrate serves to disclose the "invisible" tri-peptide substrate for kinetic analysis. The method is fast and simple and will allow detailed kinetic studies and screening for natural peptide substrates of leukotriene A4 hydrolase as well as other members of the M1 family of aminopeptidases. PMID- 17357162 TI - The structural properties of magainin in water, TFE/water, and aqueous urea solutions: molecular dynamics simulations. AB - Here, the MD simulations and comparative structural analysis of Magainin in water, TFE/water, and 2M, 4M, and BM urea solutions is reported. For MAG TFE/water and MAG-2M urea the largely alpha helical conformation of the peptide is maintained throughout the 9-ns simulation. While in water, 4M urea, and 8M urea, the helix length decreases and at the same time helix radius increases. This suggests a more destabilized magainin secondary structure. Our simulation data reveals that the stabilizing effect of TFE is induced by preferential accumulation of TFE molecules around the alpha helical peptide. These results indicate that an aqueous urea solution solvates the surface of polypeptide chain more favorably than pure water. Urea molecules interact more favorably with nonpolar groups of the peptide in comparison with water, and the presence of urea improves the interactions of water molecules with the hydrophilic groups of the peptide. At 8M urea, there are more direct interactions between the urea and solute, and the helix is destabilized. At 2M urea, the interaction of urea molecules and nonpolar residues are weak, therefore, the presence of urea molecules decreases the interactions of water molecules with hydrophilic groups. Urea could not deteriorate the peptide secondary structure with time from an initial helix structure. PMID- 17357163 TI - Proteochemometric modeling reveals the interaction site for Trp9 modified alpha MSH peptides in melanocortin receptors. AB - The interactions of alpha-MSH peptides with melanocortin receptors (MCRs) were located by proteochemometric modeling. Nine alpha-MSH peptide analogues were constructed by exchanging the Trp9 residue in the alpha-MSH core with the natural or artificial amino acids Arg, Asp, Cys, Gly, Leu, Nal, d-Nal, Pro, or d-Trp. The nine peptides created, and alpha-MSH itself, were evaluated for their interactions with the 4 wild-type MC(1,3-5)Rs and 15 multichimeric MCRs, each of the latter being constructed from three sequence segments, each taken from a different wild-type MC(1,3-5)R. The segments of the chimeric MCRs were selected according to the principles of statistical molecular design and were arranged so as to divide the receptors into five parts. By this approach, a set of 19 maximally diverse MC receptor proteins was obtained for which the interaction activity with the 10 peptides were measured by radioligand binding thus creating data for 190 ligand-protein pairs, which were subsequently analyzed by use of proteochemometric modeling. In proteochemometrics, the structural or physicochemical properties of both interaction partners, which represent the complementarity of the interacting entities, are used to create multivariate mathematical descriptions. (Here, physicochemical property descriptors of the receptors' and peptides' amino acids were used). A valid, highly predictive (Q2 = 0.74) and easily interpretable model was then obtained. The model was further validated by its ability to correctly predicting the affinity of alpha-MSH for new point and cassette-mutated MC4/MC1Rs, and it was then used to identify the receptor residues that are important for affording the high affinity and selectivity of alpha-MSH for the MC1R. It was revealed that these residues are located in several quite distant parts of the receptors' transmembrane cavity and must therefore cause their influence at various stages of the dynamic ligand binding process, such as by affecting the conformation of the ligand at the vicinity of the receptor and taking part in the path of the ligand's entry into its binding pocket. Our study can be used as a template how to create high resolution proteochemometric models when there are a limited number of natural proteins and ligands available. PMID- 17357164 TI - Comprehensive statistical analysis of residues interaction specificity at protein protein interfaces. AB - We calculated interchain contacts on the atomic level for nonredundant set of 4602 protein-protein interfaces using an unbiased Voronoi-Delaune tessellation method, and made 20x20 residue contact matrixes both for homodimers and heterocomplexes. The area of contacts and the distance distribution for these contacts were calculated on both the residue and the atomic levels. We analyzed residue area distribution and showed the existence of two types of interresidue contacts: stochastic and specific. We also derived formulas describing the distribution of contact area for stochastic and specific interactions in parametric form. Maximum pairing preference index was found for Cys-Cys contacts and for oppositely charged interactions. A significant difference in residue contacts was observed between homodimers and heterocomplexes. Interfaces in homodimers were enriched with contacts between residues of the same type due to the effects of structure symmetry. PMID- 17357166 TI - Metal-assisted, reversible phosphinyl phosphination of the carbon-nitrogen triple bond in a nitrile. PMID- 17357165 TI - Ligand-capped Pt nanocrystals as oxide-supported catalysts: FTIR spectroscopic investigations of the adsorption and oxidation of CO. PMID- 17357167 TI - Cloning and heterologous expression of the aranciamycin biosynthetic gene cluster revealed a new flexible glycosyltransferase. PMID- 17357168 TI - Separation of ortho- and para-hydrogen in van der Waals complex formation. PMID- 17357169 TI - Studies on the uptake of glucose derivatives by red blood cells. AB - Erythrocytes express the same glucose transporter (GLUT-1) as is present in the blood-brain barrier. With the aim of testing the viability of using this transport system to deliver glucosyl drug derivatives to the brain, the uptake of several dopamine-glucose conjugates and a few structurally related analogues by erythrocytes was studied with HPLC and (1)H MAS NMR spectroscopy. The results showed that slight structural changes determine the uptake of glycoconjugates by red blood cells. However, experiments in the presence of glucose transport inhibitors showed that none of the conjugates that efficiently crossed the cell membrane were transported by GLUT-1. PMID- 17357170 TI - Fluorescent probes for rapid screening of potential drug-drug interactions at the CYP3A4 level. AB - Steroid derivatives bearing fluorescent groups such as anthracene, dansyl, deazaflavin, and pyrene attached to C6 were synthesized. These compounds are unique inhibitors of cytochrome P450 3A4 (CYP3A4) and display similar IC(50) values in the microM range for the CYP3A4 substrates midazolam, testosterone, and nifedipine. On binding to CYP3A4, the fluorescence of the dansyl, deazaflavin, and pyrene probes is quenched by photophysical interaction of the fluorophore with the heme. The addition of drug candidates with binding constants in the nM microM range causes displacement of the probes from the active site, and hence leads to restoration of fluorescence. Accordingly, relative affinities of drug candidates to CYP3A4 can be easily and accurately determined by fluorescence measurements. PMID- 17357171 TI - Synthesis, biological evaluation, and molecular modeling investigation of chiral phenoxyacetic acid analogues with PPARalpha and PPARgamma agonist activity. AB - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis, and play a central role in cardiovascular disease, obesity, and diabetes. Thus, there is significant interest in developing new and specific agonists for these receptors. Herein we present screening results for a series of chiral phenoxyacetic acid analogues, some of which are potent PPARalpha agonists as well as PPARgamma agonists. The stereochemistry of these compounds plays an important role in determining their activity; the S isomers were observed to be more active than the corresponding R isomers. Interestingly, for one of these analogues, the stereoselectivity toward PPARalpha was reversed, and for this reason docking experiments were performed to rationalize this peculiar behavior. PMID- 17357172 TI - Antimutagenic effect of broccoli flower head by the ames salmonella reverse mutation assay. AB - A study was performed to investigate the antimutagenic effect of broccoli flower head by the Ames Salmonella reverse mutation assay. Broccoli flower head being the most highly edible part in the plant was analysed for its antimutagenic effect. Without isolating the phytomolecules, the crude ethanol extract of broccoli flower head was tested for suppressing the mutagenic effect induced by certain chemical mutagens. Three strains - TA 98, TA102 and TA 1535 were used in the study. The tester strains were challenged with their respective mutagens. These were challenged with the ethanol extract of broccoli flower head at concentrations of 23 and 46 mg/plate. The plates were incubated for 72 h and the revertant colonies were counted. The crude extract did not prove to be promutagenic. The ethanol extract of the broccoli flower head at 46 mg/plate suppressed the mutagenic effect induced by the corresponding positive mutagens on all the three tester strains used in this study. The crude extract of broccoli flower head alone was not cytotoxic even at the maximum concentration tested (46 mg/plate). In conclusion, the ethanol extract of broccoli at 46 mg/plate suggests their diverse antimutagenic potential against the mutagenic chemicals employed in this study. PMID- 17357173 TI - Potent in vitro cytotoxic and antioxidant activity of Careya arborea bark extracts. AB - Careya arborea is used in traditional medicine for the treatment of tumors and other ailments. The successive chloroform and ethyl acetate extracts and crude 50% methanol extract exhibited potent cytotoxicity against cancerous RD, HEp-2 and HeLa cell lines. They were found to be safe against the normal Vero cell line. The methanol and aqueous extracts possessed strong antioxidant activity against many oxidants in the in vitro antioxidant screening. The total phenol content of these extracts was found to be high. The results suggest strong cytotoxic and antioxidant properties and support the ethnomedical claims for the plant. PMID- 17357174 TI - Differential growth inhibitory effects of W. somnifera root and E. officinalis fruits on CHO cells. AB - The Chinese Hamster ovary (CHO) cell line is widely used for measuring drug cytotoxicity and resistance. Therefore, the effects of two major Ayurvedic drugs (W. somnifera root and E. officinalis fruits) on the short and long-term growth of these cells were investigated. A standard 96-well plate assay was used to measure short-term growth. For assessment of long-term growth, the colony formation assay (CFA) was used, which measures clonogenic potential. This assay is the best measure of the cytotoxicity of anticancer drugs and the radio sensitivity of tumor cells. As reported by others, the aqueous extracts of both herbal drugs were found to have short-term growth inhibitory effects on CHO cells when added to cells at the time of cell plating. However, this is the first report showing that these two herbal drugs have significantly different effects on the long-term growth of CHO cells. Thus, extracts of W. somnifera root, but not E. officinalis fruit, caused a reproducible, dose dependent, inhibition of colony formation of CHO cells. PMID- 17357175 TI - Antibacterial activity of ergosterol peroxide against Mycobacterium tuberculosis: dependence upon system and medium employed. AB - Ergosterol peroxide, cycloart-23-en-3beta,25-diol, vanillin and 4 hydroxybenzaldehyde have been isolated and characterized from a crude methanol extract of Euphorbia lagascae. Previous studies have shown contradictory results about the antibacterial activity of ergosterol peroxide against Mycobacterium tuberculosis. In order to clarify this question, the activity of this compound was tested against Mycobacterium tuberculosis H37Rv ATCC 27294 strain using two different systems: BACTEC 460TB (Bactec 460) and BACTEC MGIT 960 system (Bactec 960). The results obtained show that significant activity was demonstrable only with the Bactec 460 system. The lack of activity noted with the Bactec 960 system appears to be due to the much faster growth rate of the organism in the medium of this system as opposed to that of the Bactec 460 system. Ergosterol peroxide is also shown by the current study to be devoid of any activity against an antibiotic sensitive ATCC strain of Staphylococcus aureus. PMID- 17357176 TI - Identification of flurbiprofen and its photoproducts in methanol by gas chromatography-mass spectrometry. AB - A sample of 10 mM flurbiprofen in methanol (or ethanol) was photoirradiated with sixteen 8 W low-pressure quartz mercury lamps irradiated at 306 nm in a Panchum PR-2000 photochemical reactor. In total, four major photoproducts derived from each sample were observed from the HPLC chromatogram. The photoproducts were separated and their structures elucidated by various spectroscopic methods. Alternatively, using GC-MS, 11 major photoproducts were observed. A reaction scheme of flurbiprofen in methanol is proposed: the photochemical reaction routes occur mainly via esterification and decarboxylation, followed by oxidation with singlet oxygen to produce a ketone, alcohols and other derivatives. PMID- 17357177 TI - Simultaneous determination of phenylglyoxylic acid, mandelic acid, styrene glycol and hippuric acid in primary culture of rat hepatocytes incubate by high performance liquid chromatography. AB - A simple HPLC method for the simultaneous determination of phenylglyoxylic acid (PGA), mandelic acid (MA), styrene glycol (SG) and hippuric acid (HA) in cell culture medium was developed. Analysis was performed on a C(18) column with a mobile phase composed of methanol-potassium dihydrogen phosphate (pH 2.5; 10 mM; 10:90, v/v) at 220 nm. The flow-rate of mobile phase was set at 0.5 mL/min. The mean absolute recoveries of PGA, MA, SG and HA were 95.9, 98.4, 98.0 and 97.1%, respectively. The inter-day and intra-day precisions, determined at three concentration levels, were less than 10% of RSD. The limits of quantification for PGA, MA, SG and HA were 13.2, 13.1, 14.5 and 11.2 microM with RSD less than 20%. The limits of detection for PGA, MA, SG and HA were 4.6, 4.6, 5.1 and 3.9 microM, respectively. The method was successfully applied to study the stereoselective metabolism of SG and MA in primary culture of rat hepatocytes. The results show that there is stereoselective metabolism for both of MA and SG in primary culture of rat hepatocytes. The extent of biotransformation from S-MA to PGA is significantly greater than that from the R enantiomer and the main metabolites are PGA and HA for S-SG and R-SG, respectively. PMID- 17357178 TI - Study of tanshinone IIA tissue distribution in rat by liquid chromatography tandem mass spectrometry method. AB - A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for determining tanshinone IIA in rat tissues. After a single step liquid-liquid extraction with diethyl ether, tanshinone IIA and loratadine (internal standard) was subjected to LC/MS/MS analysis using positive electro spray ionization under selected reaction monitoring mode. Chromatographic separation of tanshinone IIA and loratadine was achieved on a Hypersil BDS C(18) column (i.d. 2.1 x 50 mm, 5 microm) with a mobile phase consisting of methanol-1% formic acid (90:10, v/v) at a flow rate of 300 microL/min. The intra-day and inter-day precision of the method were less than 10.2 and 12.4%, respectively. The intra-day and inter-day accuracies ranged from 99.7 to 109.7%. The lowest limit of quantification for tanshinone IIA was 1 ng/mL. The method was applied to a tanshinone IIA tissue distribution study after an oral dose of 60 mg/kg to rats. Tanshinone IIA tissue concentrations decreased in the order of stomach > small intestine > lung > liver > fat > muscle > kidneys > spleen > heart > plasma > brain > testes. Tanshinone IIA still could be detected in most of the tissues at 20 h post-dosing. These results indicate that the LC/MS/MS method was rapid and sensitive to quantify tanshinone IIA in different rat tissues. PMID- 17357179 TI - Transport behavior and efflux of Rg1 in rat pulmonary epithelial cells. AB - The aim of this study was to investigate whether ginsenoside Rg1 could be transported into rat pulmonary epithelial cells and its transport behavior and efflux through the cells. A high-performance liquid chromatography coupled with 2487 UV-vis detector at 203 nm was applied. The mobile phase was 0.05% phosphate acetonitrile (75:25, v/v). Cells were incubated with Rg1 (100 microg/mL) for a specific time, then lysed and sonicated in methanol to extract intracellular Rg1. Cells incubated with Rg1 and verapamil or KCN were processed by the same method. A 20 microL aliquot of sample was injected into the HPLC system to determine Rg1 concentration. The results showed that Rg1 could be transported into the epithelial cells with peak concentration of 1.28 microg/10(5) cells at 0.5 h. Metabolic inhibitor KCN and P-glycoprotein inhibitor verapamil could increase Rg1 concentration within the cells, indicating that efflux of Rg1 was energy dependent and P-gp was likely to be involved. This is the first time that the transport behavior and efflux of Rg1 through rat pulmonary epithelial cells has been demonstrated. The phenomenon that Rg1 concentration in the cells decreased whereas that in the medium remained high indicated that a more effective means of drug administration should be found. PMID- 17357180 TI - Profile of psychiatric disorders and life events in medically ill elderly: experiences from geriatric clinic in Northern India. AB - BACKGROUND: Morbidity among elderly people has an important influence on their psychological well-being. Evaluation of the morbidity profile and its determinants, which have implications for management of medical problems of elderly people, are scarce in developing countries. Even the physicians' detection rate of mental distress in elderly populations is low in medical outpatient clinics. This could be due to the large caseloads and also, importantly, underestimation of psychological concerns of the elderly. The objective of this study was to study the psychiatric co-morbidity and life events among elderly medical outpatients. METHODS: One hundred medically ill elderly (>60 years) patients attending the Geriatric Clinic at Bikaner (North India) constituted the study population. The physical diagnosis was made by a physician based on reported illness, clinical examination and medical records. Psychiatric diagnosis was made by detailed clinical psychiatric interview using ICD-10 guidelines. Life events were assessed by the Indian adaptation of Presumptive Stressful Life Events Scale. RESULTS: Hypertension was the most commonly reported physical diagnosis (50%), other specific medical illnesses were osteoarthritis (15%), diabetes (13%) and constipation (8%). The study found 18% subjects had depression and 11% had other mental disorders. Patients with mental disorders had suffered more recent stressful life events. Among life events, conflicts in family (16%); unemployment of self or children (9%) was reported by elderly psychiatric patients. Other reported life events in psychiatric diagnosed elderly were conflict in family (7%), illness of self (6%) or family members (5%) and death of family members (5%) or close relatives (4%). CONCLUSION: Mental disorders are common among medically ill elderly patients, but they are poorly recognized and treated. Assessment of the psychiatric morbidity will help in strengthening psycho-geriatric services and thus, improve the quality of life of the elderly. PMID- 17357181 TI - Cerebral volume measurements and subcortical white matter lesions and short-term treatment response in late life depression. AB - BACKGROUND: Late life depression is associated with volumetric reductions of gray matter and increased prevalence of subcortical white matter lesions. Previous studies have shown a poorer treatment outcome in those with more severe structural brain abnormalities. In this study, quantitative and semi-quantitative magnetic resonance imaging (MRI) measures were studied in relation to response to a 12-week controlled antidepressant monotherapy trial. METHODS: MRI (1.5 T) brain scans of 42 elderly inpatients with major depression, of which 23 were non responder to a controlled 12-week antidepressant monotherapy trial, were acquired. In addition, clinical outcome was assessed after a one year period. Measures were volumes of global cerebral and subcortical structures. RESULTS: After controlling for confounding, no differences were found between non responders and responders after 12 weeks and after one year in volumes of cerebral gray and white matter, orbitofrontal cortex, hippocampus and white matter lesions. CONCLUSIONS: Structural brain measures associated with late life depression may not be related to short-term treatment response. PMID- 17357182 TI - Etiology and outcome of prenatally detected paracardial cystic lesions: a case series and review of the literature. AB - OBJECTIVES: Isolated paracardial cysts, defined as cystic structures adjacent to or originating from the heart, are rare and etiologically heterogeneous congenital abnormalities. The purpose of this study was to review our experience with prenatally diagnosed isolated cysts. METHODS: We reviewed retrospectively the medical charts and ultrasound records of all cases with an antenatal diagnosis of paracardial cyst at our institution between 2001 and 2006. Where applicable, the diagnosis was further substantiated by other imaging modalities and pathology. RESULTS: The cysts in six fetuses were diagnosed at a median gestation of 20 (range, 19-38) weeks. Three of these fetuses presented with a fluid-filled cyst attached to or within the pericardial space (pericardial cysts), which resolved spontaneously by the time of delivery. In contrast, the cysts did not change in size or shape in the remaining three fetuses. Postnatal examination of the persistent cysts revealed three different etiologies: (1) a microcystic lymphangioma, located in the anterior mediastinum; (2) an isolated neurenteric cyst; and (3) a single bronchogenic cyst, both within the posterior mediastinum. The lymphangioma and neurenteric cyst were removed surgically after birth. CONCLUSIONS: Fetal echocardiography enables early detection of paracardial cyst. Pericardial cysts disappeared spontaneously during the course of gestation without signs of fetal cardiac compromise, suggesting a benign prognosis. Imaging by magnetic resonance and computerized tomography were particularly useful to clarify the etiology, structure and extent of those cysts that had not resolved by the time of birth. Published by John Wiley & Sons, Ltd. PMID- 17357183 TI - Molecular mechanisms of cancer cells survival. AB - It is of great interest for cancer therapy to elucidate and overcome the mechanisms that cancer cells develop to fight back the defense systems of the organism and anticancer treatments. The anticancer defense of the organism consists of four processes: 1. Activity of the cellular immunity; 2. Production of cytokines; 3. Activation of tumor-suppressor genes; 4. Blocking of the enzyme telomerase. Several molecular mechanisms that cancer cells develop for survival are described: 1. Reactivation of the telomerase; 2. Suppression of apoptosis; 3. Elimination of effector cells; 4. Shedding of soluble receptors; 5. Neutralization of tumor-suppressor genes; 6. Developing of a drug efflux pump; 7. Neoangiogenesis; 8. Overcoming and utilizing hypoxia; 9. Other rescue mutations; 10 Access- restriction factors.Some new approaches for overcoming the survival mechanisms of cancer cells are briefly outlined. PMID- 17357184 TI - Good Scientific Practice. Part VIII. Being a peer reviewer - you like it, or you hate it? PMID- 17357185 TI - Anthracycline pretreated patients: who is who in the chemotherapy choice of relapsed breast cancer? AB - During the last years, a strong trend towards excluding anthracyclines from the first-line chemotherapy (CT) of relapsed breast cancer (RBC) has been noticed. This trend is based on the concept of previous exposure of the tumor on the same drugs in the adjuvant setting. Consequently, some guidelines and experts recommend the avoidance of using these compounds for RBC under those circumstances, while the taxanes became the first treatment option. This article gives detailed references about the lack of correlation between the type of adjuvant chemotherapy (including anthracyclines), and the clinical outcome of patients treated with front-line anthracyclines for RBC. It also addresses the weakness of this rationale based on recent translational research data and comments on the fact that anthracyclines could represent the best treatment option for some subcategories of patients with RBC. Concluding, this new trend seems more empirical than evidence-based, and clarification of this issue is warranted. PMID- 17357186 TI - The response of urological tumours to immunotherapy. AB - The use of immunotherapy to attempt to treat cancer is not new. At the end of the last century, William Coley observed that the tumour of a patient with a sarcoma who developed streptococcal erysipelas regressed. This led Coley to develop a collection of heat-killed bacteria, known as Coley's toxins, which he used to activate the immune system, with some reported tumour regressions. Subsequently, several investigators used BCG to treat solid tumours. When used by intralesional injection, BCG induced regressions of melanoma skin metastases in some patients, but without affecting survival. In 1976, Morales described the use of intravesical BCG to treat superficial transitional cell carcinoma (TCC) of the bladder. The efficacy of intravesical BCG remains the most successful example of cancer immunotherapy to date. PMID- 17357187 TI - Dose escalation of docetaxel and ifosfamide in patients with advanced breast cancer failing prior anthracyclines: mature results of a phase I-II study. AB - PURPOSE: Single-agent docetaxel and ifosfamide are clinically active in anthracycline-pretreated advanced breast cancer. We conducted a phase I-II study aiming to define the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and the activity of the docetaxel-ifosfamide combination in this setting. PATIENTS AND METHODS: Cohorts of 3-6 patients with histologically confirmed metastatic breast cancer after prior anthracycline-based chemotherapy were treated at successive dose levels (DLs) with escalated doses of docetaxel (70-100 mg/m(2) over 1 h on day 1), followed by ifosfamide 5-6 g/m(2) divided over days 1 and 2 (2.5-3.0 g/m(2)/day over 1 h), and recycled every 21 days. G-CSF was added once dose-limiting neutropenia was encountered at a certain DL and planned to be incorporated prophylactically in subsequent higher DLs. RESULTS: Sixty-five patients (median age 57 years, range 32-72) and performance status (PS) (World Health Organization-WHO) of 1 (range 0-2) were treated at 5 DLs as follows: 21 in phase I DLs (DL1: 3, DL2: 6, DL3: 3, DL4: 6, and DL5: 3) and the remaining 44 were treated at DL4 (total of 50 patients at DL4), which was defined as the level for phase II testing. All patients were evaluable for toxicity and 62 for response. DLT (with the addition of G-CSF after DL2) was reached at DL5 with 2/3 initial patients developing febrile neutropenia. Clinical response rates (RRs), on an intention-to-treat basis, in phase II were 56% (95% CI 42.2-69.7): complete remission (CR) 4, partial remission (PR) 24, stable disease (SD) 10 and progressive disease (PD) 12. The median response duration was 7 months (range 3 24), the median time to progression (TTP) 6.5 months (range 0.1-26), and the median overall survival (OS) 13 months (range 0.1-33). Grade 3/4 toxicities included neutropenia in 72% of patients-with 60% developing grade 4 neutropenia (3-fold, 12 patients versus 2, p<0.03.). No patient stopped chemotherapy because of toxicity, and there were no treatment-related deaths. CONCLUSION: Adjuvant chemotherapy in RC with LV+5-FU for 6 months is equally effective and less toxic than LVS+5-FU for 12 months. PMID- 17357208 TI - Primary lymphoma of the liver: clinical features and outcome of 9 patients. AB - PURPOSE: Primary liver lymphoma (PLL) is a rare lymphoproliferative disorder of unknown etiology. The prognosis in affected patients is poor, consisting of brief remissions, rapidly developing resistance to chemotherapy, early recurrence, and short survival. Most studies related to PLL are based on case reports. The aim of this retrospective study was to review our experience with PLL. PATIENTS AND METHODS: From 1985 to 2000, 9 patients who fulfilled the diagnostic criteria for PLL were treated at our hospital. All patients underwent a thorough work-up and were staged accordingly. RESULTS: The disease occured in middle and higher-aged patients (median age 63 years). Primary presenting complaints were abdominal pain, mainly in the right upper quadrant, and hepatomegaly. Liver function tests and lactate dehydrogenase (LDH) levels were elevated. Liver imaging (computed tomography-CT) and isotopic methods (gallium scan) demonstrated liver involvement either as solitary or multiple space-occupying lesions. Pathologic examination demonstrated diffuse, large cell (DLCL), B-type lymphoma in 7/9 (78%) patients. Doxorubicin-based chemotherapy was the mainstay of treatment. Good partial or complete remission rates were achieved in 7 patients, albeit for a brief period of time. CONCLUSION: Most patients with PLL succumb to their illness, despite its being relatively chemotherapy-sensitive. The introduction of intensive chemotherapy, plus/minus radiotherapy, and/or surgery has been considered in some studies. PMID- 17357209 TI - Brachytherapy after laser recanalization versus external beam radiotherapy after laser recanalization versus laser alone in inoperable oesophagocardial cancer: a controlled pilot study. AB - PURPOSE: To compare the results of combined laser/radiation therapy with laser treatment alone, and to evaluate the potential benefit of brachytherapy vs. external beam radiotherapy after laser recanalization in patients with dysphagia due to oesophagocardial cancer. PATIENTS AND METHODS: Twenty patients with grade 4 malignant dysphagia caused by oesophagocardial cancer underwent Nd: YAG laser desobstruction up to grade 0-1. Ten of them were referred afterwards for external beam radiotherapy at a dose of 30 Gy for 10 sessions, while the remaining were administered endocavitary afteloading brachytherapy at a dose of 2x7.5 Gy. Twenty preselected patients (to maximally match the above group), who successfully underwent laser re-establishment of the continuity, served as controls to the groups described. Criteria for evaluation were: mean interval to re-stenosis, mean number of additional laser procedures needed, mean survival and Karnofski's performance status (PS). Patients were followed to death. Statistical analysis was carried out with the Student's t-test. RESULTS: It was found that laser plus brachytherapy increased almost 3 times the interval to re-stenosis and decreased almost 2 times the need of additional laser usage in comparison to laser alone. It was also found that laser plus brachytherapy is statistically superior option to laser plus external beam radiotherapy. CONCLUSION: Laser plus brachytherapy has the potential to become a single modality-single session treatment for the relief of dysphagia in patients with stage IV oesophagocardial cancer. PMID- 17357210 TI - Nanoparticles as drug carrier system of 5-fluorouracil in local treatment of patients with superficial basal cell carcinoma. AB - PURPOSE: To develop an alternative nonsurgical treatment for basal cell carcinoma using colloidal systems as drug carriers. We investigated the possibility of polybutylcyanoacrylate nanoparticles loaded with 5-fluorouracil (5-FU) to be applied in local treatment of patients with basal cell carcinoma. PATIENTS AND METHODS: 32 patients (mean age 74 years, range 56-90) with histologically confirmed superficial basal cell carcinoma were treated with 5-FU-loaded polybutyl-cyanoacrylate nanoparticles. The nanoparticles were prepared by anionic polymerization of butyl-2-cyanoacrylate monomer for use as drug delivery system. The preparation of 5-FU-loaded polybutylcyanoacrylate nanoparticles was carried out by adsorption of the drug on the surface of previously prepared nanoparticles. This preparation was applied once a day for 35-40 days. The effect of treatment on the immunological parameters, measured by phytohaemagglutinin (PHA)-induced DNA synthesis of T lymphocytes and also their number in the peripheral blood were analyzed in 28 of 32 treated patients and compared against a group of 24 healthy individuals (controls). RESULTS: 31 of 32 patients achieved histologically confirmed complete tumor resolution. Treatment did not cause significant changes both in the number of T lymphocytes and PHA-induced DNA synthesis of T lymphocytes of the treated patients. CONCLUSION: Local treatment with 5-FU-loaded nanoparticles provides a nonsurgical treatment alternative in patients with superficial basal cell carcinoma. This effective and well tolerated method is preferred by patients who are not surgical candidates or who prefer nonsurgical treatment. PMID- 17357211 TI - Palliative treatment of advanced esophageal cancer with metal-covered expandable stents. A cost-effectiveness and quality of life study. AB - PURPOSE: The aim of this retrospective study was to evaluate the efficacy and safety of endoscopic therapy with self-expanding metallic endoprostheses in the management of inoperable primary malignant esophageal obstruction or stenosis and the cost-effectiveness of the method. PATIENTS AND METHODS: Between 5/1997 12/2002, obstruction of the esophagus was diagnosed in 78 patients (52 males, 26 females, age range 53-102, mean 72.3 years). The etiology was squamous cell carcinoma (n=42) and adenocarcinoma of the oesophagus (n=36). In total, 89 ultraflex metal stents were introduced endoscopically. In 46 patients dilation with Savary dilators prior to stent placement was required. A cost-effective analysis was performed, comparing oesophageal stenting with laser therapy. RESULTS: Stents were placed successfully in all patients. After 48 h, all patients were able to tolerate solid or semi-solid food. During the follow-up period 8 patients developed dysphagia due to food impaction (treated successfully endoscopically). Eleven patients developed recurrent dysphagia 4-16 weeks after stenting due to tumor overgrowth and were treated with placement of a second stent. The median survival time was 18 weeks. There was no survival difference between squamous cell and adenocarcinoma of the esophagus. A similar cost was calculated for both procedures. A significant improvement in quality of life was noted in patients undergoing stenting (96% and 75% vs. 71% and 57% for the first two months). CONCLUSION: Placement of self-expanding metal stents is a safe and cost-effective treatment modality that improves the quality of life, compared with laser therapy, for patients with inoperable malignant esophageal obstruction. PMID- 17357212 TI - The influence of the American environment on cigarette smoking among the immigrants from the former Yugoslavia. AB - PURPOSE: We tested the hypothesis that the American environment influences the immigrants from developing countries with high incidence of smokers to quit smoking. METHODS: The sample included 218 immigrants who came as adults from the former Yugoslavia. A total of 275 persons were randomly selected, and the overall study response was 79.2%. The survey included questions about current smoking, smoking history, and demographic data, such as year of immigration to the USA, education, and employment status. RESULTS: Upon their arrival, 34.8% of the adult Yugoslav immigrants were smokers; now 20.2% of these immigrants smoke(p<0.001). Smoking prevalence for women was 9.1% higher than for men. The number of cigarettes that men and women smoke per day was similar. CONCLUSION: For an immigrant smoker, the best chance of quitting smoking was within 5 years of acculturation. The local media in their languages may provide the best health education to immigrants, including information on the effects of cigarette smoking. To reduce smoking prevalence in the former Yugoslav republics and other developing countries, rigorous antismoking measures may effectively reduce smoking prevalence and contribute to better health of their citizens. PMID- 17357213 TI - Evaluation of combined telomerase and c-myc expression in non-small cell lung carcinomas using tissue microarrays and computerized image analysis. AB - PURPOSE: Telomerase activation plays a crucial role in tumorigenesis by sustaining cellular immortality. It consists of two main components which include a RNA subunit (h-TERC) and a catalytic protein subunit (h-TERT). Similarly, amplification or deletion correlating with overexpression of c-myc is a common event in various neoplasias, including non-small cell lung carcinoma (NSCLC). Because c-myc activates telomerase by inducing expression of its catalytic subunit, our aim was to correlate the expression of these two proteins with the biological behavior in NSCLC. MATERIALS AND METHODS: Using tissue microarrays technology (TMA) we evaluated by computerized image analysis (CIA) the results of h-TERT and c-myc immuno-histochemistry (IHC) in 40 NSCLCs, which were cored and re-embedded into one TMA block. RESULTS: Co-overexpression (moderate or high levels of NLI: Nuclear Labeling Index) of h-TERT and c-myc was observed in the majority of cases and found to be statistically significant (p=0.001). The results showed also strong association between c-myc and h-TERT overexpression correlating with stage (p=0.001 for both of them), but not with grade (p=0.206 and p=0.313, respectively). CONCLUSION: Our combined study showed that there is a strong correlation between the activation and expression of these two genes and maybe this co-deregulation could be used as a prognostic factor for the evaluation of biological behavior in NSCLCs. PMID- 17357214 TI - Synthesis and antiproliferative activity of new carboplatin analogues. AB - PURPOSE: The aim of this study was to present the synthesis and characterization of two carboplatin analogues and to investigate their antiproliferative activity against human tumor cell lines. MATERIALS AND METHODS: The carboplatin analogues cis-1,2-propylendiammine (cyclobutane-1,1-dicarboxylato) platinum (II) (MD2), and cis-izobutylendiammine (cyclobutane-1,1-dicarboxylato)platinum (II) (MD3) were characterized by elemental analysis and (1)H-NMR-measurements. The compounds were tested for antiproliferative activity against the following human tumor cell lines: myelogenous leukemia K562, colon adenocarcinoma HT- 29, breast adenocarcinoma MCF-7, and human lung fetal fibroplast cell line MRC-5. The active substance of carboplatin (MD1) was used as reference compound. Cells were exposed to complexes for 24 h at concentrations ranging from 10(-3) to 10(-8)M. Growth inhibition was evaluated by the colorimetric SRB assay. The IC(50) value of each carboplatin compound was determined by median effects analysis. RESULTS: Both carboplatin analogues induced dose-dependent growth inhibition of human tumor cell lines after 24 h of treatment. The MD3 analogue was 60-fold and the MD2 was 2-foild more active against K562 cell line compared to the referent compound. The activity of both analogues was comparable to the refernt compound against MCF-7 cell line. Colon adenocarcinoma cell line HT-29 was found to be 4-fold less sensitive to MD2 but equally sensitive to MD3 with respect to carboplatin referent compound. Both carboplatin and its analogues induced moderate cytotoxicity on MRC-5 cell line ranging from 25% (10(-7)M) to 46%(10(-3)M). CONCLUSION: This study showed that the two novel carboplatin analogues inhibited human cell lines in a different manner depending on cell line. Carboplatin analogues were more active against human tumor cell lines than against human lung fibroplast cell line MRC-5. PMID- 17357215 TI - Carcinoma of sigmoid colon after ureterosigmoidostomy. AB - An unusual case of adenocarcinoma of the colon in a 49-year-old man is described. The patient underwent ureterosigmoidostomy at the age of 3 years after a traffic accident. At the age of 49 years, he was admitted to a Department of Urology for treating urinary lithiasis. A chest x-ray and thoracic computed tomography (CT) showed some nodules in both pulmonary fields, while an abdominal CT was normal. The previous patient's history was ignored, the patient underwent thoracoctomy and a nodule was removed. The histology revealed a metastatic, moderately differentiated mucinous adenocarcinoma, probably of the bowel. A sunsequent colonoscopy was non-disclosing and the patient was thought to suffer from a carcinoma of unknown origin and received 6 cycles of chemotherapy with carboplatin and 5-fluorouracil. Five months after the end of chemotherapy he presented with an uncerated mass in the lower abdominal wall. A new CT scan revealed a solid mass in the pelvis with infiltration of the suprapubic region while a repeat colonoscopy showed an infiltrating mass in the sigmoid. Biopsies were obtained from both lesions and the histology was similar with that of the pulmonary nodule. PMID- 17357216 TI - Spitz nevus of the tongue with pseudoepitheliomatous hyperplasia: a case report. AB - Spitz nevus is a rare tumor, most commonly arising from the skin. We report on a case of Spitz nevus of the tongue in a 14-year-old girl. She underwent local excision and the histopathological and immunohistochemical (IHC) studies by using AEC chromogen peroxidase conjugate indicated Spitz with pseudoepitheliomatous hyperplasia. PMID- 17357217 TI - The osteosarcoma of the great poet Arthur Rimbaud (1854-1891). AB - Thanks to Arthur Rimbaud's excellent medical auto-observation, which is included in his correspondance, we can diagnose, post-mortem, an osteosarcoma in the right knee, a disease which turned out to be fatal for him. PMID- 17357218 TI - Abstracts of the 60th Annual Cancer Symposium of the Society of Surgical Oncology. March 15-18, 2007. Washington, DC, USA. PMID- 17357219 TI - Abstracts of the 32nd Annual Scientific Meeting of the Society of Interventional Radiology, 2007 SIR. March 1-6, 2007. Seattle, Washington, USA. PMID- 17357220 TI - Abstracts of the 5th International Congress on Lung Cancer. January 24-27, 2007. Patras, Greece. PMID- 17357221 TI - Management of diabetic foot infections. Short text. Societe de Pathologie Infectieuse de Langue Francaise. PMID- 17357223 TI - Abstracts of the Sixth International Conference of the Hospital Infection Society. October 15-18, 2006. Amsterdam, The Netherlands. PMID- 17357222 TI - [Management of diabetic foot infections. Long text. Societe de Pathologie Infectieuse de Langue Francaise]. PMID- 17357224 TI - [An old woman with sudden pareses and blindness]. AB - We present a patient with Posterior Reversible Encephalopathy Syndrome (PRES). A 74-year-old woman was admitted with sepsis, which originated from erysipelas on her neck the following day. She developed respiratory obstruction due to oedema, septic shock, disseminated intravascular coagulation (DIC), acute renal failure and atrial fibrillation. She responded well to treatment and improved rapidly, despite of her serious condition. When she had almost fully recovered after 15 days, her general condition worsened, and she developed confusion, blindness and pareses. MRI showed vasogenic oedema in the parietooccipital regions of the brain and in the cerebellum, consistent with PRES. PRES is a clinical and radiological diagnosis consisting of headache, confusion, cortical blindness, convulsions and sometimes pareses. MRI of the cerebrum with diffusion-weighted imaging (DWI) and Apparent Diffusion Coefficient (ADC) map are decisive to the diagnosis, and usually shows a characteristic bilateral vasogenic oedema in the parietooccipital region. This can distinguish PRES from brain infarction, which shows a cytotoxic oedema on MRI. We discuss our patient in the light of different conditions leading to PRES, possible pathophysiological factors and treatment options. PMID- 17357225 TI - [Potential reversible encephalopathy syndrome?]. PMID- 17357226 TI - [Fortified milk to Indian children for better health]. PMID- 17357227 TI - CPOE: sufficient, but not perfect, evidence for taking action. PMID- 17357228 TI - Authorship issues related to software tools. PMID- 17357229 TI - [100 years ago: the Bordet-Wassermann test]. PMID- 17357230 TI - [Cystic ectasia of the rete testis]. PMID- 17357231 TI - [Cardiovascular benefits of some levels of alcohol consumption: not proven]. PMID- 17357232 TI - [High-intensity lentiform nucleus lesions on T1-weighted images in a patient with liver failure]. PMID- 17357233 TI - [Primary osteoblastoma-like osteosarcoma of the sternum: a case report]. PMID- 17357234 TI - [Abstracts of the 111th Congress of the French Society of Ophthalmology. 7-11 May 2005, Paris, France]. PMID- 17357235 TI - Erratum to "Is there increased risk of local and in-transit recurrence following sentinel lymph node biopsy?" [Journal of Plastic, Reconstructive & Aesthetic Surgery 59 (2006) 487-493]. PMID- 17357236 TI - [Abstracts of the Meeting of Respiratory Research (J2R), Tours, France, 13-14 October 2006]. PMID- 17357237 TI - Attaining the inside track on asthma control. AB - Asthma is one of the most common--and most commonly untreated or inadequately treated--respiratory illnesses. Yet even mild cases can be fatal. Much research remains to be done to fully understand how to prevent, treat, and cure asthma. But with timely diagnosis and proper management, asthma can be controlled, allowing patients to lead healthy, active lives. PMID- 17357238 TI - Fairness opinions in health care transactions--cause and effect: the emergence of private equity funds as a driving force in big and small transactions and the resulting increased use of fairness opinions. PMID- 17357239 TI - Use of the monoclonal antibody anti-human epidermal growth factor receptor 2 (anti-HER2), trastuzumab, in the treatment of metastatic breast cancer: a cost effectiveness analysis. PMID- 17357241 TI - A natural selection. PMID- 17357240 TI - ["Knowing the patients" in an economizing health care system]. PMID- 17357242 TI - Ethnographic origins: St Vincent and Tasmania. PMID- 17357243 TI - The early history of Hamilton-Jacobi dynamics 1834-1837. PMID- 17357244 TI - The French botanist Aime Bonpland and paleontology at Cuenca del Plata. PMID- 17357245 TI - [Eugenics, heredity, selection, and biometry in the work of Francis Galton]. PMID- 17357246 TI - The Krakatoa event and associated phenomena: a historical review. PMID- 17357247 TI - [Curiosities for the king: an account of objects shipped in the 18th century to the Royal Cabinet of Natural History in Madrid from the New World]. PMID- 17357248 TI - International science "down under": the British association meeting in Australia, August 1914, with special reference to related activities in Adelaide. PMID- 17357249 TI - [Africa and social anthropology]. PMID- 17357250 TI - Pharmaceuticals: pharmaceutical cost controls. PMID- 17357251 TI - Risk of cardiovascular events in patients at optimal values for combined lipid parameters. AB - BACKGROUND: Current prevention guidelines support efforts to achieve optimal high density lipoprotein (HDL-C) and triglyceride (TG) values, in addition to low density lipoprotein (LDL-C) in order to reduce cardiovascular (CV) events. The study objective was to evaluate the risk of CV events in patients attaining versus not attaining combined (LDL-C, HDL-C, and TG) optimal lipid values. METHODS/RESULTS: This retrospective cohort analysis was conducted using a 1.1 million member managed care database. Eligible patients had a full lipid panel between 10/1/99 and 9/30/00, were naive to lipid therapy, and had health plan eligibility 12 months pre- and post-index (baseline) lipid laboratory value. Optimal lipid values (LDL-C, HDL-C, and TG) were established using the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) guidelines, and patients were placed into one of four groups: none, one, two, or three lipid components non-optimal at baseline. The presence of cardiovascular risk, disease, and events were determined by selected International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) and Current Procedural Terminology (CPT codes). The definition of a CV event included: diagnosis of ischemic heart disease, peripheral arterial disease, stroke/TIA, or revascularization procedure. Odds ratios (OR) for a CV event associated with attainment of each optimal lipid fraction were determined by multivariate logistic regression. The study cohort included 30,348 patients, with a mean follow-up of 27 +/- 8 months. Mean age was 66 +/- 12 years; 16,549 (54%) were male; and 17,289 (57%) patients had coronary heart disease (CHD) or CHD risk equivalent. There were 5955 CV events that occurred in 4059 (13%) study patients. The presence of a single non-optimal lipid value slightly increased CV event risk [OR: 1.06; 95% CI: 0.95-1.18], whereas two or all three non-optimal lipid values significantly increased the risk of a CV event [OR: 1.22; 95% CI: 1.08-1.37; and 1.45; 95% CI: 1.24-1.68, respectively]. LIMITATIONS: As with all large observational databases there are potential limitations including: patient selection bias (e.g., more interventions in patients with greater illness, lack of mortality data, and frequency of lipid monitoring), unknown confounding variables, and potential coding errors. CONCLUSION: Not attaining optimal combined lipid values, independently and significantly, increased the risk of CV events in this large at-risk population with approximately 68,283 patient years of follow-up. The combination of non attainment of optimal LDL-C with non-attainment of optimal HDL-C or TG values, or both, increased the adjusted risk of CV events by 22-45%. Thus, therapeutic strategies should focus on assessment and management of multiple lipid abnormalities, and not on single lipid risk factor modification. PMID- 17357252 TI - [International Congress on George Joseph Camel (1661-1706). Brno, 8-10 June 2006]. PMID- 17357253 TI - Preventing cervical cancer. AB - Every month in Australian Family Physician, and in every other medical journal in the world, there are discussions of new information; descriptions of innovations; or changes in the way we view health and illness that cumulatively or individually will make a positive impact. It is not often that the potential impact appears so obvious and clear cut as the development of an effective primary prevention vaccine for cervical cancer. While editing this month's articles, I was able to tell my 13 year old daughter and her friends about a vaccine that would dramatically reduce the risk that they would develop cervical cancer. On a world scale, it has the potential to prevent premature death and reduce morbidity for millions of women. PMID- 17357256 TI - Gas chromatography problem solving and troubleshooting. Column performance of small molecule GC-MS. PMID- 17357255 TI - Stem cells. PMID- 17357257 TI - Liquid chromatography problem solving and troubleshooting. Step jumps in Chromatogram. PMID- 17357254 TI - Nonreceptor tyrosine kinases in prostate cancer. AB - BACKGROUND: Carcinoma of the prostate (CaP) is the most commonly diagnosed cancer in men in the United States. Signal transduction molecules such as tyrosine kinases play important roles in CaP. Src, a nonreceptor tyrosine kinase (NRTK) and the first proto-oncogene discovered is shown to participate in processes such as cell proliferation and migration in CaP. Underscoring NRTK's and, specifically, Src's importance in cancer is the recent approval by the US Food and Drug Administration of dasatinib, the first commercial Src inhibitor for clinical use in chronic myelogenous leukemia (CML). In this review we will focus on NRTKs and their roles in the biology of CaP. MATERIALS AND METHODS: Publicly available literature from PubMed regarding the topic of members of NRTKs in CaP was searched and reviewed. RESULTS: Src, FAK, JaK1/2, and ETK are involved in processes indispensable to the biology of CaP: cell growth, migration, invasion, angiogenesis, and apoptosis. CONCLUSIONS: Src emerges as a common signaling and regulatory molecule in multiple biological processes in CaP. Src's relative importance in particular stages of CaP, however, required further definition. Continued investigation of NRTKs will increase our understanding of their biological function and potential role as new therapeutic targets. PMID- 17357258 TI - American College of Endocrinology and American Diabetes Association consensus statement on inpatient diabetes and glycemic control. PMID- 17357260 TI - [Emergency Conditions in Gastroenterology. The Prague Fall Gastroenterology Seminar. 12 October 2006. Abstracts]. PMID- 17357259 TI - Integrating cultural competence into nursing education and practice: 21st century action steps. PMID- 17357261 TI - Practitioner, researcher, and educator. PMID- 17357262 TI - An unusual sore throat. AB - A young homeless man recently presented to a health clinic located in a youth service. He complained that, over the past day, his throat had become increasingly painful with an obstructed sensation. On examination, his uvula was very swollen and red. He had no other significant symptoms and examination was otherwise normal. PMID- 17357263 TI - [Comments to the guidelines by the National Board of Health on methicillin resistant Staphylococcus aureus]. PMID- 17357264 TI - [Focal nodular hyperplasia]. PMID- 17357265 TI - [Graduate education then and now--50 years' since the first cardiology course in Krci (UCHOK)]. PMID- 17357266 TI - [Will general practice become a subcontractor to private surgery?]. PMID- 17357267 TI - [30 years as prison physician]. PMID- 17357268 TI - [From the history of the Nobel Prize]. PMID- 17357269 TI - [10th Atherosclerosis Congress. Spindleruv Mlyn, 7-9 December 2006. Czech Atherosclerosis Society in cooperation with the Czech Angiology Society and J.E. Purkinje Czech Medical Society. Abstracts]. PMID- 17357270 TI - Liver resection and transplantation using a novel 3D hepatectomy simulation system. AB - In liver surgery, accurate assessments of liver resection volume and anatomical variation are mandatory for preoperative planning of safe curative hepatectomy. In living donor liver transplantation (LDLT), estimation of hepatic venous drainage is important to avoid liver graft and donor residual liver congestion. This paper reviews the articles on simulation-guided liver surgery and describes our novel 3D hepatectomy simulation system for liver resection and transplantation. Our 3D simulation system, based on the hepatic circulation, provided accurate volumetric and stereotactic information for preoperative planning of curative hepatectomy. In addition, our simulation program was applicable to the hepatic venous system to predict liver congestion in LDLT. Future studies include assessment of the impact of the simulation technologies on surgical education, and their exact cost-effectiveness must be also assessed objectively. PMID- 17357271 TI - Recent concepts in the management of bowel problems after spinal cord injury. AB - Bowel problems after SCI can be debilitating. Colonic inertia as a result of decreased parasympathetic (S2-4) stimulation of the left colon and rectosigmoid seems to be the principal abnormality accounting for DWE. The conventional measures used for decades have poor results in many people. Neostigmine, an anticholinesterase inhibitor, appears to be a more physiological agent for these individuals. The combination of neostigmine + glycopyrrolate infusion has shown encouraging results after intravenous administration and studies are under way to assess the efficacy of neostigmine by other routes. PMID- 17357272 TI - Current topics on precursors to pancreatic cancer. AB - Prognosis of invasive pancreatic ductal adenocarcinoma is bleak and the vast majority of patients with pancreatic cancer die of their disease. The detection and treatment of the non-invasive precursor lesions of pancreatic cancer offer the opportunity to cure this devastating disease and therefore great efforts are being made to identify the precursors to pancreatic cancer. Several distinct precursor lesions have been identified. Mucinous cystic neoplasms (MCNs), intraductal papillary mucinous neoplasms (IPMNs), and pancreatic intraepithelial neoplasias (PanINs) all harbor varying degrees of dysplasia and stepwise accumulation of genetic alterations, suggesting progression of these lesions from benign toward malignant neoplasms. MCNs have a characteristic ovarian-type stroma. About one-third of MCNs are associated with invasive carcinoma of ductal phenotype. IPMNs are recently established clinical entity with characteristic features of mucin hypersecretion and duct dilatation. Some IPMNs are associated with invasive carcinoma and IPMNs are recognized precursors to pancreatic cancer. PanINs are microscopic proliferative lesions arising from any parts of the pancreatic duct system. Low grade PanINs are commonly found in pancreatic ducts of elder individuals, while high grade PanINs, previously called carcinoma in situ/severe ductal dysplasia, may eventually give rise to invasive pancreatic cancer. Appropriate clinical managements are requisite for patients with MCNs, IPMNs and PanINs. Further investigation of these precursor lesions is expected to reduce the mortality from pancreatic cancer. PMID- 17357273 TI - Sperm analyses, genetic counselling and therapy in an infertile carrier of a supernumerary marker chromosome 15. AB - PURPOSE: A supernumerary marker chromosome (SMC) was analysed after lymphocyte culture of a patient with oligoasthenoteratozoospermia (OAT) before ICSI treatment. MATERIAL AND METHODS: By additional molecular cytogenetic investigations the marker could be identified as a heterochromatic derivate of chromosome 15 [karyotype: 47,XY,+der(15)]. RESULTS: Sperm analyses by interphase FISH showed a normal monosomy 15 in 82% and an additional marker in 17% of the cells. In spite of these findings a pregnancy could not be induced. The brother of the patient showed the same chromosome abnormality and an OAT-syndrome as well. CONCLUSIONS: ICSI-treatment lead to a normal pregnancy and to the birth of a healthy boy. The genetic risk factors of both marker carriers are analysed in detail. PMID- 17357274 TI - DNA typeability in liquid urine and urine stains using AmpFISTR SGM Plus. AB - PURPOSE: Urine specimens are usually collected for biochemical and toxicological tests and for doping control. In forensic casework urine analyses are performed occasionally, however, the authors emphasize their importance in crime scene reconstruction. The objective of the research was to evaluate efficacy of AmpFISTR SGM Plus typing of urine and urine stains which were subject to different temperature conditions. MATERIAL AND METHODS: Urine samples were collected from 10 female and 10 male volunteers. Liquid specimens were stored at room temperature (RT), 4 degrees C and -20 degrees C up to 28 days. Experimental stains were prepared by applying 3 ml urine on sterile cloth 30 x 30 cm, air dried and stored at RT up to 360 days. The amount of DNA was estimated with use of slot-blot technique (Quantiblot Human DNA Quantitation Kit, Applera). DNA profiles were obtained using AmpFISTR SGM Plus and 310 ABI Prism Genetic Analyzer (Applera). Typing of a experimental sample was considered successful when the full profile was obtained matching that of a reference sample. RESULTS: Significant differences in DNA yield were noted between female and male urine samples. No differences between the extraction methods were found in regard to DNA yield and typeability rate. Different typeability rates were recorded for liquid urine and urine stains depending on storage temperature. CONCLUSIONS: Liquid urine samples and urine stains can be considered as a potential source of DNA in disputable specimen individualization and in forensic casework using the fluorescent multiplex PCR system AmpFLSTR SGM Plus. PMID- 17357275 TI - Overview how adenocarcinoma cancer cells avoid immune- and chemotherapy-induced apoptosis. AB - This review describes some aspects of uncontrolled tumor growth and development. In the past, it has been shown that colon adenocarcinomas use several tactics to avoid cell deletion and to maintain cell viability. In particular, colorectal cancer cells resist death ligands-induced apoptosis by expressing anti-apoptotic proteins. By direct interaction with FADD, the FLIP protein inhibits the signal transmission from death receptors to their cytoplasmic targets in COLO 205 cells. Colorectal cancer cells also stimulate own survival by inhibiting cytotoxic signals induced by interferons. Moreover, IFN-alpha increases immune-resistance of colon cancer cells by activation of NF-kappaB. Additionally, the cytoplasmic retention of proapoptotic protein clusterin also supports viability of cancer cells. Upon suitable stimulation normal cells are featured by clusterin translocation to the nucleus with concomitant cell death. We found that proapoptotic activity of clusterin is dependent on calcium ions, and depletion of intracellular calcium caused extensive death of COLO 205 cells. Other type of strategy to inhibit chemotherapy-dependent cell death is the activity of multidrug resistance proteins (MDR). These cell membrane efflux pumps actively expel the drugs from the cell interior to prevent their action on intracellular targets. The reversal of P-gp efflux pump in chemoresistant COLO 320 cell line was observed upon phenothiazine derivatives. The variety of antiapoptotic mechanisms in colorectal cancer cells makes anticancer therapy a great challenge but detailed knowledge of their complexicity gives promise to sensitize cancer cells to death stimuli. PMID- 17357276 TI - Levels of HBV-DNA, sFas and sFasL among healthy HBsAg carriers in period of three years. AB - PURPOSE: The object of the study was the usefulness of sFas and sFasL concentration in the prognosis of disease development in healthy HBsAg carriers. PATIENTS: 34 healthy HBsAg carriers were examined over a three-years period. MATERIAL AND METHODS: HBV-DNA was extracted using the Gene Elute Mammalian Genomic DNA Miniprep Kit (Sigma, USA). HBV-DNA concentration and YMDD mutations were measured by RT-PCR based on TaqMan Universal Master Mix (Applied Biosystems, USA). HBeAg and anti-HBe in serum were detected by MEIA method (ABBOTT, Germany). The concentration of sFas and sFasL in serum was estimated by ELISA method (Bender MedSystems, Austria). RESULTS: Within three year observation period the number of carriers with absent HBV-DNA increased from 19% to 33%. HBV-DNA above 105 copies/ml, which was detected in 63% of carriers, decreased to 11% (p < 0.05). After 3 years, a reduction of HBV-DNA levels was observed in 89% of carriers (p < 0.05). The occurrence of sFasL decreased from 56% to 48%. sFasL correlated with HBV-DNA (p < 0.05). The concentration of sFas decreased (p < 0.01). Chronic hepatitis B developed in 11% of men carriers, and 11% eliminated HBeAg, anti-HBe and HBV-DNA. YMDD mutant was not detected in any of the HBsAg carriers. CONCLUSIONS: High concentration of sFasL in serum may suggest the development of chronic hepatitis and it seems that sFasL detection is never a good prognostic factor. PMID- 17357277 TI - Biomarkers in clinical practice: a tool to find subjects at high risk for stomach cancer. A personal view. PMID- 17357278 TI - Antioxidant mechanism of hepatoprotection by ursodeoxycholic acid in experimental alcoholic steatohepatitis. AB - PURPOSE: The aim of this study was to evaluate the role of an antioxidant factor in the hepatoprotective effect of ursodeoxycholic acid (UDCA) in rat alcoholic steatohepatitis. MATERIAL AND METHODS: The effects of UDCA (40 mg/kg, i.g., 30 days) were studied using rats fed on a high-fat diet (52% calories as fat) and administered with ethanol via intragastric intubation (4 g/kg daily, 30 days). RESULTS: The livers of ethanol-treated animals were characterized by fatty dystrophy. The relative liver weight and the square of the sudanophylic area as well as the liver triglyceride content and the activity of the serum marker enzymes, aspartate aminotransferase and gamma-glutamyltransferase, were significantly increased. Elevated superoxide dismutase activity as well as increased contents of lipid peroxidation products (hydroxyalkenals, malone dialdehyde, etc.) and lucigenin-enhanced microsomal chemiluminescence were observed in the liver of ethanol-treated rats and the liver reduced glutathione content was decreased. An increase in monoenoic fatty acids, a decrease of the n 6 acid family and an enhancement of microsomal membrane viscosity were found in the liver of these animals. An elevation of the total cytochrome P-450 content and the activity of amidopyrine-N-demethylase were shown in liver microsomes of the ethanol-treated group. The UDCA treatment improved the liver morphology, decreased serum marker enzyme activities, liver triglyceride content and normalized all the indices of oxidative stress. UDCA lowered the viscosity of the microsomal membrane, as assessed by both the fluorescence probe techniques and the saturated/unsaturated fatty acid ratio. The microsomal cytochrome P-450 content and amidopyrine-N-demethylase activity were normalized in UDCA-treated rats. CONCLUSIONS: We can conclude that the hepatoprotective effect of UDCA stipulated by its antioxidant properties is indeed the factor enabling UDCA to control metabolic processes by changing the properties of liver membranes and membranous proteins. PMID- 17357279 TI - TGF-beta1 down-regulates ICAM-1 expression and enhances liver metastasis of pancreatic cancer. AB - PURPOSE: In order to study the regulation of adhesion-molecule expression by cytokines, we have investigated the effect of transforming growth factor-beta1. (TGF-beta1) on the expression of intercellular adhesion molecule-1 (ICAM-1) in human pancreatic cancer cell lines. MATERIAL AND METHODS: By using three pancreatic cancer cell lines, SW1990, CAPAN-2 and PANC-1, the effect of TGF-beta1 on expression of ICAM-1, cancer cell immunogenicity and liver metastasis were investigated. RESULTS: Cell surface ICAM-1 expression by ELISA on three cell lines were all reduced significantly by following incubation with various concentrations of TGF-beta1 and down-regulation of ICAM-1 expression was also observed at the mRNA level. Corresponding to the down expression of ICAM-1, the adhesion of peripheral blood mononuclear lymphocytes (PBMLs) to cancer cells and cancer cell cytotoxicity during co-culture with PBMLs were remarkably decreased by treatment with TGF-beta1. Furthermore, enhanced liver metastatic potential by in vivo splenic injection was observed in CAPAN-2 cells pretreated with TGF beta1. CONCLUSIONS: Since decreased expression of ICAM-1 has been known to contribute to cancer cell escape from immunologic recognition and cytotoxicity by effector cells, the present results indicate that unknown function of TGF-beta1 in the tumor progression and metastasis of pancreatic cancer. PMID- 17357280 TI - The role of positron emission tomography (PET) in diagnostics of gastroenteropancreatic neuroendocrine tumours (GEP NET). AB - PET is a successful modality to detect cancer and in recent years has demonstrated a great diagnostic value in large series of tumour types. PET combines high sensitivity and reasonable resolution, and offers the ability to perform whole body scans. 18F-deoxyglucose (FDG)-PET has also been used to diagnose tumours of neuroendocrine origin. Even if 18F-FDG has been successfully and widely employed in oncology, it has not demonstrated a significant uptake in well differentiated neuroendocrine tissues. Thus 18F-FDG is not a good tracer for neuroendocrine tumours, as FDG-PET imaging of number of GEP tumours revealed increased glucose metabolism only in less differentiated GEP tumours with high proliferative activity and in metastatising MTC associated with rapidly increasing CEA levels. In such a situation, additional 18F-FDG PET should be performed only if somatostatin receptor scintigraphy (alone or with 99mTc-DMSA) is negative. On the contrary, other positron emitter tracers seem to be more promising. 68Ga-DOTA-NOC (tetraazycyclododecanetetraacetic acid-[1-Nal3] octreotide) has been used as a positron emitter tracer for the detection of NETs in preliminary studies. A serotonin precursor 5-hydroxytryptophan (5-HTP) labelled with 11C has shown an increased uptake in carcinoids. This uptake seems to be selective and some clinical evidence has demonstrated that it allows the detection of more lesions with PET than with CT or octreotide scintigraphy. Another radiopharmaceutical in the development for PET is 11C-L-DOPA, which seems to be useful in imaging endocrine pancreatic tumours. PMID- 17357281 TI - Tartrate-resistant acid phosphatase 5b and its correlations with other markers of bone metabolism in kidney transplant recipients and dialyzed patients. AB - PURPOSE: Renal osteodystrophy is a common complication of chronic renal failure and renal replacement therapy. Successful kidney transplantation reverses many of these abnormalities, however, the improvement is often incomplete. The osteoclast specific 5b isoform of tartrate-resistant acid phosphatase (TRAP) 5b has recently been proposed a specific and sensitive marker of bone resorption. The aim of the study was to assess correlations of TRAP 5b with markers of bone resorption and formation in kidney transplant recipients, hemodialyzed and peritoneally dialyzed patients and healthy volunteers. MATERIAL AND METHODS: We assessed PTH, markers of bone formation-alkaline phosphatase and its bone isoform, osteocalcin, markers of bone resorption--procollagen type I carboxy-terminal extension peptide, procollagen type I cross-linked carboxy-terminal telopeptide, serum CrossLaps Ctx, beta2-microglobulin and urinary deoxypyridynoline (DPD), expressed as DPD/creatinine ratio. (BMD) bone mineral density measurements were determined for femoral neck and lumbar spine (L2-L4) using DEXA. RESULTS: In dialyzed patients markers of bone formation and resorption were significantly higher than in healthy volunteers, whereas in kidney transplant recipients these disturbances were less pronounced. TRAP 5b correlated positively with age and mainly with markers of bone resorption in kidney transplant recipients, dialyzed patients and healthy volunteers. TRAP 5b did not correlate with BMD in any groups studied. CONCLUSION: Since TRAP 5b correlated mainly with markers of bone resorption, it may serve as a new additional marker of bone resorption in the assessment of renal osteodystrophy. PMID- 17357282 TI - The effect of extracorporeal efferent detoxication (EED) methods inclusion in the severe community-acquired pneumonia (CAP) treatment. AB - PURPOSE: To assess the clinical efficacy including of EED methods in the treatment of severe CAP with endogenic intoxication syndrome. MATERIAL AND METHODS: Severe CAP in patients (n = 103, aged 18-60 years, male 89%) were randomly subdivided into the 4 comparable groups. The 1st group (n = 30) was standard treated with antibiotics. The 2nd group (n = 27) underwent additionally 3 courses of extracorporeal ultraviolet light-exposure (UVLE). The 3rd group (n = 25) was co-treated with 3 courses of biospecific hemosorption (BSS). The 4th group (n = 21) underwent 2 additional courses of BSS plus 3 courses of UVLE. The effectiveness of these schemes therapy was assessed by clinical and laboratory data. RESULTS: The additional application of EED methods led to faster disappearance of clinical symptoms, focal chest signs and the infiltrate resolution in chest X-ray (CXR) as compared with standard treatment. Mean time of the disappearance of fever and sweating was 2.2; 2.5; 2.0 days and 4.8; 5.0; 4.6 days in the 2nd, 3rd and 4th group respectively after EED courses vs 6.1 and 8.0 days in 1st group (P < 0.05). The baseline elastase activity was elevated by 5 times in the 1st-4th groups vs the control (healthy) group and was decreased by 1.5; 2.1; 4.1; 6.6 times respectively (P < 0.05) after treatment in these groups. The initial trypsin-like activity was increased about 5.5 times in all groups vs control and decreased after therapy by 2.1; 3.8; 6.4; 6.0 times (P < 0.05) in the 1st-4th groups respectively. Small CXR residual changes persisted in 7, 4 and 5 patients from the 2nd, 3rd and 4th groups vs 12 patients in the 1st group. The spirometry data were normalized faster in the patients who underwent EED methods (by the 14th day) vs the 1st group. CONCLUSIONS: Additional using of EED methods in severe CAP therapy is more effective (as compared with traditional management with antibiotics only) in term of faster improvement of patients general condition, reduced time of inflammatory infiltrate resolution and hospitalization by 3-4 days. It has been shown that EED methods correct the main pathogenic mechanisms of severe CAP. Our results indicated on the EED methods as an attractive supportive therapy for the empiric antibiotics treatment of this disease. PMID- 17357283 TI - The efficacy and safety of argon plasma coagulation (APC) in the management of polyp remnants in stomach and colon. AB - PURPOSE: Endoscopic treatment of sessile and semipedunculated polyps remains controversial. Residual tissue remains frequently after endoscopic snare polypectomy. The aim of the study was to assess the outcome and safety of argon plasma coagulation (APC) in the management of gastric and colorectal polyp remnants after polypectomy, and to search for clinical parameters useful in predicting the efficacy of this technique. MATERIAL AND METHODS: This prospective study comprised 18 patients with gastric polyps and 29 with colonic polyps found in upper and lower GI endoscopy. Overall 22 gastric polyps and 58 colonic polyps have been detected. All those polyps were removed at colonoscopy with the diathermic snare and the polyp remnants were destroyed with APC using Argon Beamer source (Erbe, Germany). Follow-up endoscopies have been performed 1, 3 and 6 months after the treatment completion. RESULTS: Pathologic examination revealed 10 hyperplastic polyps and 12 tubular adenomas of the stomach. Effective destruction of polyp remnants was achieved in 20 (90.9%) gastric polyps in 16 (88.9%) patients. Significant positive correlation was demonstrated between the power output, APC sessions number and polyp location in the prepyloric part, its size and adenomatous content. Among colonic polyps there were: 17 hyperplastic, 26 tubular, 8 tubulo-villous, 4 villous adenomas and 3 inflammatory pseudopolyps. Effective destruction of remnant polyp tissue was obtained in 56 (96.4%) polyps in 27 (93.1%) patients. A significant positive correlation between the power output and the size, distal location and villous texture of the polyp has been demonstrated. No complications other than mild abdominal distention have been encountered. CONCLUSIONS: APC is an effective and safe method in the management of polyp remnants in the stomach and colon. The application of higher electric power and numerous APC sessions are necessary to remove residues of large gastric polyps located in the prepyloric part and of with adenomatous content. In the case of colonic polyps the application of higher electric power should be recommended in case of large-sized lesions, located in rectum and of villous texture. PMID- 17357284 TI - Plasma adiponectin and E-selectin concentrations in patients with coronary heart disease and newly diagnosed disturbances of glucose metabolism. AB - PURPOSE: Adiponectin is a fat derived hormone, which enhances insulin sensitivity. In experimental studies adiponectin was shown to have antiatherogenic properties by suppressing endothelial expression of adhesion molecules. Therefore, the aim of the study was to evaluate plasma adiponectin and E-selectin concentrations in patients with coronary artery disease and impaired glucose metabolism and evaluation of their relationship with selected anthropometric, biochemical and clinical parameters. MATERIAL AND METHODS: The study group consisted of 62 patients with coronary heart disease, without previous diagnosis of diabetes mellitus (mean age 48.6 +/- 6.0 years; mean BMI 28.6 +/- 3.13 kg/m2). In the studied group the OGTT with glucose and insulin estimation was performed and insulin resistance index (HOMA-IR) was calculated. In the fasting state, the plasma adiponectin, soluble form of E-selectin, HbA1c and lipid parameters were estimated. RESULTS: Adiponectin concentration was not different in patients with type 2 diabetes mellitus and impaired glucose tolerance (n = 36) in comparison to the group with normal glucose tolerance (n = 26). There was also no difference in adiponectin concentration in relation to atherosclerosis progression. There was no significant correlation between adiponectin and calculated insulin resistance index, while there was marked inverse correlation between adiponectin and BMI (r = -0.30; p = 0.018), body weight (r = -0.33; p = 0.008), E-selectin (r = -0.263; p = 0.039), TG concentration (r = -0.27; p = 0.036), duration of coronary heart disease (r = 0.33; p = 0.009) and borderline significance with ejection fraction (r = -0.268; p = 0.06). CONCLUSIONS: Our study supports the hypothesis that adiponectin could be recognised as a protective protein for the development of atherosclerosis. PMID- 17357285 TI - Acute biliary pancreatitis in the era of minimally invasive surgery. AB - PURPOSE: Opinions about early endoscopic sphincterotomy and time of laparoscopic cholecystectomy in acute biliary pancreatitis are still controversial. Some authors reserved this procedure only for cases in which the stones were visualized during ERCP or patients had clinical symptoms of acute cholangitis. The aim was the assessment of the dynamic of changes of proinflammatory cytokines and white blood cells in time in patients with acute biliary pancreatitis after performed endoscopic sphincterotomy and laparoscopic cholecystectomy. MATERIAL AND METHODS: We enrolled 43 consecutive patients with clinically diagnosed mild forms of acute biliary pancreatitis. All were treated by early endoscopic sphincterotomy and laparoscopic cholecystectomy performed during the first 48 hours after admission. The course of the disease was monitored by measurement of the level of proinflammatory cytokines. RESULTS: Marked decrease of the level of proinflammatory interleukins within 24 hours after endoscopic sphincterotomy was observed. Mean values of IL-6 and IL-8 were statistically lower immidiately after this procedure (p < 0.001). Subsequent decrease was achieved after laparoscopic cholecystectomy. The mean values of TNF-alpha and IL-12p40 were relatively constant throughout the study period. CONCLUSION: All patients suffering from mild acute biliary pancreatitis should be treated by using minimally invasive procedures. However, such a only treatment should be reserved for experienced centers. PMID- 17357286 TI - Early endoscopic sphincterotomy and early laparoscopic cholecystectomy in the treatment of severe acute biliary pancreatitis--a preliminary report. AB - PURPOSE: The proper timing of endoscopic sphincterotomy and laparoscopic cholecystectomy in acute biliary pancreatitis is still a subject of controversies. The following rapid report presents preliminary data concerning treatment of patients with severe form of necrotizing biliary pancreatitis (SNBP) with the sequence of minimal invasive procedures (endoscopic sphincterotomy and laparoscopic cholecystectomy) performed in the first 48 hours after admission. MATERIAL AND METHODS: Twelve patients with SNBP were included in the study. The described above procedures were performed in all of the patients within 48 hours. We evaluated clinical outcome, complications, time of stay in hospital and also some morphological (white blood cells) and liver parameters (AST, ALT, bilirubin, ALP and GGT) of these patients in the course of the disease. RESULTS: Two patients died. Two other ones has local complications. We did not observe major complications after ERCP with ES and after laparoscopic cholecystectomy. Additionally, the lavage of the abdominal cavity was performed and drainage was established during laparoscopic cholecystectomy. Conversion in our group occurred in 1 person. Later complications in the course of the disease were caused by the its progression and not related to the performed procedures. CONCLUSIONS: The results are very incurable, however, performing these types of procedures in the experienced centers deserves to be taken into account. PMID- 17357287 TI - The role of adenosine A2a receptors in experimental acute pancreatitis. AB - PURPOSE: The role of adenosine and its receptors in acute pancreatitis remains unelucidated. The aim was to evaluate the effects of the adenosine A2a receptor agonist and antagonist in the severe, taurocholate-induced experimental acute pancreatitis (EAP). MATERIAL AND METHODS: The experiments were performed on 80 male Wistar rats, subdivided into 4 groups: C--the control rats, I--the EAP group, IIA--EAP group treated with the A2a adenosine receptor agonist CGS 21680, IIB--EAP group treated with the A2a adenosine receptor antagonist ZM 241385. The blood for alpha-amylase and lipase and tissues samples for the morphological examinations and immunohistochemistry for A2a receptors were collected in 2, 6, 24 hours of the experiment. RESULTS: The serum alpha-amylase tended to decrease in the group IIA as compared to EAP untreated after 6 and 24 h. No significant effect of both treatments on serum lipase was noted. The administration of CGS 21680 resulted in favorable decrease of the inflammatory cell infiltration, hemorrhagic changes, necrosis and vacuolization of acinar cells, without an evident effect on the edema of the interstitial tissue. The administration of ZM 241385 did not affect the scores of necro-hemorrhagic changes and inflammatory infiltration, whereas it decreased the scores of vacuolization and edema. In all groups the expression of A2a receptors was similar. CONCLUSIONS: Our findings suggest, that A2a adenosine receptors are involved in the course of sodium taurocholate EAP. It is probable that the modulation of some subgroups of adenosine receptors could alleviate the course of severe experimental AP. PMID- 17357288 TI - Metabolic effects associated with adipose tissue distribution. AB - Cardiovascular and metabolic risk depends not only on the overall obesity but also fat distribution is more powerfull predictor for risk factors. Adipose tissue produces and secretes a variety of bioactive peptides - adipokines The most recently described adipocyte secretory proteins contribute to the pathogenesis of impaired insulin secretion and insulin resistance, endothelial dysfunction, a proinflammatory state and promote progression of atherosclerosis. This review presents an overview of the adipose tissue secreted proteins (leptin, TNF-alpha, IL-6, adiponectin, resistin, visfatin, ASP, FIAF, MT) role and their regulation in the context of abdominal obesity and the adverse metabolic consequences. PMID- 17357289 TI - Magnification chromoendoscopy in comparison to standard chromoendoscopy for detection of intestinal metaplasia in renal transplant recipients. AB - PURPOSE: Renal transplantation is associated with frequent gastrointestinal complications. Intestinal metaplasia is a feature of atrophic gastritis whereas the diagnosis of Barrett's esophagus is based on histological demonstration of specialized metaplasia. Both conditions are associated with increased risk of adenocarcinoma. The aim of the present study was to assess whether magnification endoscopy improves the diagnostic accuracy of intestinal metaplasia in stomach and in esophagus. MATERIAL AND METHODS: In this non-randomized, feasibility study thirty one (12 women and 19 men) renal transplant recipients, with a mean age of 44.0 years were evaluated for the presence of intestinal metaplasia. Standard esophagogastroscopy with methylene blue staining was followed by magnification endoscopy. The presence of gastritis and intestinal metaplasia was classified according to modified updated Sydney classification. RESULTS: Of 31 patients, 16 patients had endoscopic and histopathological evidence of gastric intestinal metaplasia, and standard endoscopy with methylene blue staining was sufficient for diagnosis (15 from 16). Magnification endoscopy allowed identification of 6 patients with specialized intestinal metaplasia in Barrett's esophagus, which would be otherwise missed. CONCLUSIONS: In this study diagnostic accuracy of standard endoscopy for identification of intestinal metaplasia in the stomach was not improved by the use of magnification endoscopy, but the latter was an accurate method of predicting specialized intestinal metaplasia in Barrett's esophagus. The use of magnification endoscopy in the clinical setting of renal transplantation needs further studies. PMID- 17357290 TI - Soluble Fas, Fas ligand and Bcl-2 in autoimmune thyroid diseases: relation to humoral immune response markers. AB - PURPOSE: To compare soluble Fas, FasL and Bcl-2 in Graves' disease (GD) and Hashimoto's thyroiditis (HT) to the markers of humoral response: aTPO, aTG and aTSHR. MATERIAL AND METHODS: 5 groups of subjects: 1) 14 patients with GD in euthyreosis on methimazol (euGD); 2) 20 patients with hyperthyroid GD (hrGD); 3) 15 patients with HT in euthyreosis on levothyroxine (euHT); 4) 16 patients with hypothyroid HT (hoHT); 5) 12 healthy volunteers age and sex-matched to group 1-4. Serum concentrations of Fas, FasL, Bcl-2, aTPO and aTG were determined by ELISA and aTSHR by RIA. RESULTS: Levels of sFas were the highest in hoHT: 8.7 (7.2-9.8) ng/ml as compared to the controls (p < 0.01) and euHT (p < 0.05). We found positive correlations between sFas and aTPO in all studied groups (r = 0.25, p < 0.05) and between sFas and TSH in HT (r = 0.4, p < 0.05). In GD there was a positive correlation between sFasL and aTG (r = 0.5, p < 0.01) and negative correlations between sFasL and Fas (r = -0.39, p < 0.01) and between sFasL and period of methimazol administration (r = -0.32, p < 0.05). Levels of sBcl-2 were significantly increased in euHT: 31.0 (13.5-44.1) ng/ml as compared to the controls (p < 0.05) and euGD (p < 0.05). CONCLUSIONS: Fas/FasL mediated apoptosis plays an important role in the active stage of the autoimmune process of both Hashimoto's thyroiditis and Graves' disease, however, in Hashimoto's thyroiditis they contribute to irreversible damage of thyreocytes. Early detection of Hashimoto's and Graves' diseases allows for the initiation of the proper treatment that probably leads to the reduction of the autoimmune process intensity. PMID- 17357291 TI - Does smoking affect thrombocytopoiesis and platelet activation in women and men? AB - PURPOSE: Smoking is a significant risk factor of cardiac ischaemia. Changes in platelet count, morphology and platelet activation enhance the risk. MATERIAL AND METHODS: The objective of the study was to assess platelet parameters in smoking healthy subjects with reference to sex. In the group of women, 27% were smokers, in the group of men--49%. All the subjects were tested for platelet count (PLT), mean platelet volume (MPV), percentage of large platelets (L(PLT)), concentrations of beta-thromboglobulin, sP-selectin (soluble) and thrombopoietin, percentage of reticulated platelets (RP) and absolute count of reticulated platelet. RESULTS: Lower platelet count (237.00 +/- 39.52 vs 258.34 +/- 40.81 x 10(9)/l, p = 0.0002), higher percentage of reticulated platelets (1.39 +/- 0 .66 vs 1.04 +/- 0.35%, p = 0.04) and higher concentration of sP-selectin (52.66 +/- 18.54 vs 43.94 +/- 17.14 ng/ml, p = 0.03) were observed only in the group of smoking women, compared to non-smokers. In neither of the sexes smoking had an effect on the following parameters: mean platelet volume, percentage of large platelets, concentration of thrombopoietin, absolute count of reticulated platelet and concentration of beta1 -thromboglobulin. CONCLUSIONS: The results allow the hypothesis that women are more sensitive to smoking than men. Platelets in male smokers are less sensitive to smoking--the study showed no significant changes in the parameters. PMID- 17357292 TI - End stage renal disease by patients with malignancy--ethical problems. AB - The problem of co-occurrence of kidney failure, as well as ESRD and malignancy is relatively often and brings a significant therapeutical and moral challenge. The ethical basis of our consideration are "Evangelium Vitae" by John Paul II and "Declaration Jura et Bona". The fundamental choice is whether to start and/or continue the kidney replacement treatment. We present 3 algorithms for the most typical situations. The first ethical postulate in our considerations is that patients with the malignancy of good prognosis should not be denied of any treatment chance and should be dialysed as any other patient. In the situation of patients with neoplastic disease with bad prognosis and ESRD, the question of 'withholding or withdrawing' dialysis is essentially part of a fundamental question, what should be the ultimate goal of medicine? There is no doubt that the person most authorized to take a decision in such a situation is the patient provided it is a conscious decision based on full information. Therefore any decision to cease treatment, even submitted at the public notary, should be verified as long as a conscious contact with a patient is possible. In the situation of continued lack of logical contact with the patient who has not left any clear disposition for such circumstances we must take the decision based on their benefit. It is more than desired that the decision acquires the approval of the patient's family but in the situation when it is not possible the doctor decide. In the doubtful cases we should take decisions "towards life". PMID- 17357293 TI - Safety of various methods of intensive insulin therapy in hospital condition assessed by hypoglycaemic episodes detected with the use of continuous glucose monitoring system. AB - PURPOSE: The aim of the study was to determine the safety of three intensive insulin therapy methods: multiple daily insulin injections (MDI), continuous subcutaneous insulin infusion (CSII) and continuous intravenous insulin infusion (IVII) used in poorly controlled type 2 diabetic patients in hospital condition. The safety of these intensive insulin therapy methods was measured by the assessment of number and duration of symptomatic and symptomfree hypoglycaemic events with use of Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed). MATERIAL AND METHODS: The study comprised 90 type 2 diabetic patients treated with conventional insulin therapy based on a twice daily injections with mean glucose profile values > 14 mmol/l. The patients were randomized into three groups according to the method of insulin treatment. The first group was treated with MDI, the second group with CSII and the third with IVII. The glucose monitoring with the use of CGMS lasted 48 hours and was conducted on the second and on the third day of intensive insulin therapy. Glucose level below 3.5 mmol/l were recognized as hypoglycaemic episode. Intensive insulin treatment was continued until "near normoglycaemia" (glucose levels 4.5-10.0 mmol/l) was achieved and then conventional insulin therapy was readministrated. RESULTS: Mean number of symptomatic hypoglycaemic events detected with CGMS was two times higher for MDI than for IVII (p = 0.04) and for CSII (p = 0.04). Number of symptomfree hypoglycaemic events detected with CGMS was higher for MDI than for IVII and CSII, but the differences were insignificant (NS). Mean duration of one symptomfree hypoglycaemic event detected with CGMS was longer in MDI than in CSII (p = 0.02) and IVII (p = 0.03). It was not observed significant differences in mean duration of one symptomatic hypoglycaemic episode between studied groups (NS). CONCLUSIONS: The results of study suggest that CSII and IVII treatment is associated with essentially lower number of symptomatic hypoglycaemic events and shorter mean duration of one symptomfree hypoglycaemic event than MDI. PMID- 17357294 TI - Mucosal gastrin cells and serum gastrin levels in children with Helicobacter pylori infection. AB - PURPOSE: Impaired control of gastric juice secretion is observed in chronic gastritis due to Helicobacter pylori (H. pylori) infection. G cells are stimulated by such cytokines as tumor necrosis factor (TNF-alpha), interferon gamma (IFN-gamma) and interleukin-8 (IL-8). The number of D cells producing somatostatin decreases simultaneously. An increase in gastrin levels could also depend on alkalization in G cell environment caused by bacterial urease. The aim of the study was to evaluate G cell counts in the antrum and gastrin levels in the serum of children with H. pylori infection and after bacterium eradication. MATERIAL AND METHODS: The study was performed in 106 patients. Children were divided into 3 groups with regard to the presence and course of H. pylori infection. Fifty nine children (55.7%) had chronic gastritis in the course of H. pylori infection with a positive titre of antibodies in IgG class against H. pylori; 29 children (27.3%) with past H. pylori infection, without bacterium colonization and gastritis but with a positive titre of antibodies in IgG class against H. pylori; 18 children (17%) with functional disorders of the gastrointestinal tract but without H. pylori infection. RESULTS: The quantitative analysis of gastrin cells in the antral mucosa of children performed by immunohistochemical method showed the highest gastrin cell count in group I with H. pylori infection (112.1 +/- 58.9 cell/mm2) and in group II with past H. pylori infection (105.3 +/- 73.1 cell/mm2). The serum gastrin level (92.9 +/- 41.6 microU/ml) was the highest in children with H. pylori infection. In controls, it was 70.0 +/- 15.3 microU/ml and could be compared to the results of children with past H. pylori infection. CONCLUSIONS: 1. The H. pylori infection plays a significant role in the stimulation of G cells increase and gastrin release in the blood serum in children. 2. The eradication of H. pylori infection is probably a main factor in gastric secretion down-regulation during gastritis in children. PMID- 17357295 TI - The comparison of Health-Related Quality of Life (HRQL) in patients with GERD, peptic ulcer disease and ulcerative colitis. AB - PURPOSE: The aim of the study was to compare HRQL in patients with three common gastroenterological chronic conditions: gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD) and ulcerative colitis (UC), as well as to assess the correlation between HRQL scores and the disease activity in patients with ulcerative colitis. MATERIAL AND METHODS: The study group comprised of 45 patients with GERD, 35--with PUD and 30--with UC. Among patients with UC, 7 were in remission, 13--in mild active and 10--with severe phase of the disease, according to Rachmilewitz. HRQL was assessed using 8 domains of Polish version of 36-Item Short Form Survey (SF-36). RESULTS: The highest mean HRQL scores in all groups were obtained in physical and social functioning SF-36 domains. Among patients with GERD and PUD the worst HRQL results were noted in bodily pain subscale; in patients with UC--in general health perception subscale. UC patients with remission showed significantly higher HRQL scores compared with those with mild active and severe phase of the disease; especially in social functioning, mental health and vitality (p < 0.001). Patients with severe UC clinical course had mean HRQL scores statistically lower than those with mild active disease only in vitality and social functioning domains. Mean SF-36 bodily pain parameters were significantly lower in GERD and PUD compared with UC. CONCLUSIONS: All the evaluated diseases have a significant negative impact on patients' HRQL parameters, which needs to be considered in those diseases management. The severity of UC clinical course contributes to impaired HRQL. PMID- 17357296 TI - Profiling of peritoneal fluid of women with endometriosis by chemokine protein array. AB - PURPOSE: Chemokines play essential role not only in controlling leukocyte function and trafficking but also in the angiogenesis and modulation of inflammatory responses. MATERIAL AND METHODS: A novel array-based enzyme-linked immunosorbent assay was used to quantitate peritoneal fluid chemokines of 25 infertile women with endometriosis and 18 controls. For our preliminary studies we chose mini-array containing nine different chemokines: MDC/CCL22, TARC/CCL17, MCP-1/CCL2, RANTES/CCL5, MIP-1alpha/CCL3, -1beta/CCL4, -1delta/CCL15, 3alpha/CCL20, and -3beta/CCL19. RESULTS: We found significantly higher MIP 3beta/CCL19 (P = 0.0036) concentrations in peritoneal fluid of women with endometriosis as compared to patients with primary infertility without any signs of disease. CONCLUSIONS: Our preliminary results suggest that MIP-3beta/ /CCL19 might play a role in the pathogenesis of endometriosis but its precise role remains to be established. Novel types of screening methods based on high throughput technologies offer great opportunities to study immunobiology of endometriosis. It will hopefully provide new possibilities for discovery of new markers and potential drug targets. PMID- 17357297 TI - Peptic ulcers and oral health status. AB - PURPOSE: Helicobacter pylori infection plays a crucial role in pathogenesis of peptic ulcers; however, among infected individuals only a small percentage will develop peptic ulcers at any time during their life. This low virulence suggests that many additional factors beside H. pylori are implicated in pathogenesis of the disease. The aim of the study was to determine whether there is a relationship between the prevalence of peptic ulcers and oral health status. MATERIAL AND METHODS: The evaluation of dental status was performed in H. pylori infected population. The study involved 93 peptic ulcer patients (77 duodenal ulcer, 16 gastric ulcer) with ulcer niche not related to non-steroidal anti inflammatory drugs (NSAIDs) consumption and 93 gender and age matched dyspeptic controls. H. pylori infection was determined in endoscopically taken slices from gastric mucosa with two methods (CLO-test and histology). RESULTS: Both in duodenal and gastric ulcer patients, the number of filled teeth was lower and debris index was higher than in controls, the number of decayed teeth was also higher in gastric ulcer patients. The number of natural teeth, number and type of prosthetic restorations, as well as the periodontal index, did not differ between the ulcer and control groups. Poor oral health in patients with peptic ulcers corresponded with education level, smoking habit, and visits to the dentist. CONCLUSIONS: Poor oral health is associated with the prevalence of peptic ulcers not related to NSAIDs consumption, but it appears doubtful that it is a significant pathogenetic factor in ulcer disease. PMID- 17357298 TI - Antimitotic activity of high affinity ligands for peripheral benzodiazepine receptor (PBR) in some normal and neoplastic cell lines. AB - PURPOSE: Overexpression of PBR has been found in several tumor types including ovarian, colon, breast adenocarcinomas, esophageal cancer. There is evidence suggesting that PBR ligands regulate cell proliferation. However, their action is probably cell-type specific. We decided to evaluate mitotic activity of PBR ligands in some normal and neoplastic cell lines. MATERIAL AND METHODS: The cells were maintained according to standard procedures. Ligand binding assay was performed in cell extract using PK-11195 or Ro-54864 and [N-methyl-3H] Ro-54864 or [N-methyl-3H] PK-11195. Cell proliferation was evaluated using 5-[3H] thymidine assay. Western Immunoblot assay was conducted using polyclonal anti-PBR antibody. RESULTS: We have found that, macrophages evoked strong binding of both Ro-54864 and PK-11195. This phenomenon was accompanied by drastic decrease in the cell divisions. Similar effect was found only in the case of non-estrogen dependent breast cancer cells MDA-MB 231. It suggest that PBR-ligand mediated inhibition of mitogenesis may represent a new anticancer strategy in non-estrogen dependent breast cancer. In respect to macrophages inhibition of the cell division by both PBR ligands may have implication in modulation of inflammatory response. It has been postulated that PBR ligands may have anti-inflammatory activity in rheumatoid arthritis. The presence of peripheral benzodiazepine receptors in chondrocytes, T cells, macrophages and mesenchymal cells suggest that peripheral benzodiazepine receptor ligands may interfere with the cytokine network and thus modulate inflammatory response. CONCLUSIONS: The data suggest that PBR-ligand mediated inhibition of DNA synthesis in non-estrogen dependent breast cancer cells and in macrophages may represent a new therapeutic approach of breast anti-cancer and anti-inflammatory therapy. PMID- 17357299 TI - Myeloid and lymphoid dendritic cells and cytotoxic T lymphocytes in peripheral blood of non-small cell lung cancer patient--a pilot study. AB - PURPOSE: Dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) are the first protecting barrier against different pathogens (viruses, bacteria and neoplasms cells). Immature myeloid- and lymphoid dendritic cells possess ability to phagocytose and present antigens to lymphocytes. They have also ability to produce IL-12, which is also known as natural killer cell stimulatory factor or cytototoxic lymphocyte maturation factor. The aim of the study was to demonstrate the relationship between percentage of immature dendritic cells and percentage of CTLs subtypes in peripheral blood of non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: The study population consisted of 10 patients suffered from NSCLC (the mean age: 61.8 +/- 10.55). The monoclonal antibodies and three-color flow cytometry technique was applied to determine the cells phenotype in peripheral blood. RESULTS: Significant negative correlation (R = -0.693, p < 0.05) between percentage of lymphoid DCs and percentage of CTLs was shown. The myeloid to lymphoid DCs ratio significantly positively (R = +0.638, p < 0.05) correlated with the percentage of CTLs. The significant negative correlation between the percentage of myeloid DCs and the percentage of CTLs-IL-12R-positive cells, as well as expression of this receptor were also ascertained (R = -0.68, p < 0.05 and R = -0.757, p < 0.01, respectively). CONCLUSIONS: In presented pilot study we demonstrated clearly relationship between the percentage of immature DCs and the percentage and the phenotype of CTLs in peripheral blood of lung cancer patients. PMID- 17357300 TI - Correlation of B type natriuretic peptides with clinical and echocardiographic parameters in heterogeneous population of patients with symptoms suggestive of heart failure. AB - PURPOSE: NT-proBNP and BNP concentrations in CHF correlate with NYHA class and LVEE Little research has been conducted to compare the clinical performance of these two natriuretic peptides in heterogeneous CHF population. Purpose: to evaluate and compare the clinical performance of NT-proBNP and BNP in heterogeneous group of CHF patients on the basis of these peptides' correlation with NYHA class, LVEF and WMI measured by echocardiography. MATERIAL AND METHODS: Consecutive patients admitted for suspected of CHE Blood samples were drawn for NT-proBNP, BNP, creatinine and echocardiography was performed. RESULTS: 71 patients were included. CHF was diagnosed in 53. Sensitivity of NT-proBNP and BNP in diagnosing CHF was 83% and 94% respectively (P = 0.079). Levels of both peptides correlated equally well with NYHA class (R = 0.537, p < 0.001; R = 0.473, P < 0.001), LVEF (R = -0.623, p < 0.001; R = -0.601, P < 0.001) and WMI (R = 0.590, P < 0.001; R = 0.527, P = 0.001). Creatinine correlated with both peptides, age correlated with NT-proBNP. No difference between sexes was found in both peptides' concentrations. In multivariate analysis independent determinants of BNP were LVEF, presence of valvular disease and NYHA class. In case of NT proBNP age and creatinine also displayed independent influence. CONCLUSIONS: NT proBNP and BNP show good sensitivity in detecting CHE Levels of both peptides correlate equally well with clinical and echocardiographic parameters of CHF, which makes them equally adequate in biochemical staging of CHF's severity regardless of its underlying cause. Levels of natriutretic peptides reflect contractile dysfunction, valvular disease and clinical condition. Age and creatinine concentration but not patients' sex should additionally be considered when measuring NT-proBNP. PMID- 17357301 TI - Determinants of nutritional status of older people in long-term care settings on the example of the nursing home in Bialystok. AB - PURPOSE: The aim of the study was the assessment of the nutritional status of older people living in the chosen long-term care setting in Poland as well as the determinants having an effect on the nutritional status of the examined subjects. MATERIALS AND METHODS: The subjects included older residents (aged 65 years and older) of the nursing home for the somatically ill adults in Bialystok. The MNA Mini Nutritional Assessment test was used as an assessment tool to detect nutritional risk. The assessment included elements of clinical and functional evaluation (Katz Index, Instrumental Activities of Daily Living (ADL) scale, Geriatric Depression Scale, Abbreviated Mental Test Score, Norton scale and mobility scale). RESULTS: One hundred out of the 109 persons fulfilling the age criterion were examined. We found that 12% of them were malnourished, 61% were at risk of malnutrition and 27% were well nourished according to the MNA test. Malnutrition affected more often persons having difficulties with chewing, ADL dependent, with limited mobility, suspected of dementia, having suffered from cerebral stroke and who lived with other people coming to the nursing home. The risk of malnutrition was observed significantly more often in individuals suspected of depression and living in urban area before nursing home placement. The significant determinants of lower scores of MNA in the regression analysis were: suspected depression, IADL dependency, limited mobility, female gender and higher number of drugs. CONCLUSIONS: The study has confirmed that malnutrition remains a common problem among older people living in nursing homes. Malnutrition is an increasing hazard especially for women, for people taking higher number of drugs and for those with different mental and physical disabilities. PMID- 17357302 TI - Myeloid and lymphoid dendritic cells in the peritoneal fluid of women with ovarian cancer. AB - PURPOSE: The aim of the study was to estimate the myeloid and lymphoid subpopulation of dendritic cells (DCs) in the peritoneal fluid (PF) of women with ovarian tumors. MATERIAL AND METHODS: We studied 34 patients with serous cystadenocarcinoma and 29 women with serous cystadenoma. Dendritic cells were isolated from peritoneal fluid, stained with monoclonal antibodies anti-BDCA-1 and anti-BDCA-2 and estimated using flow cytometry. RESULTS: Peritoneal fluid myeloid DCs constituted 0.59% of mononuclear cells in patients with ovarian cancer and 7.2% in women with serous cystadenoma. Lymphoid DCs constituted 0.39% of PF mononuclears in women with ovarian cancer and 0.07% in patients with serous cystadenoma. The percentage of lymphoid DCs was higher in patients with ovarian cancer than in women with serous cystadenoma. The BDCA-1/BDCA-2 DCs ratio in peritoneal fluid of patients with serous cystadenoma was significantly higher in comparison to ovarian cancer. CONCLUSIONS: Decreased BDCA-1/BDCA-2 DCs ratio in patients with ovarian cancer may favour Th2 lymphocyte differentiation and/or induction of immunological tolerance. PMID- 17357303 TI - Effect of hydralazine on CD3-zeta chain expression in Jurkat T cells. AB - PURPOSE: Deficient CD3-zeta chain expression in T cells of patients with idiopathic SLE is associated with T cell receptor/ /CD3 complex (TCR/CD3) mediated signaling defect. Hydralazine (HYD) inhibits expression of DNA methyltransferase 1 (DNMT1) and may cause a lupus-like disease in man. MATERIAL AND METHODS: To explain the HYD effect on intracellular level of CD3-zeta chain in Jurkat T leukemia cells clone E6-1, we employed the flow cytometric analysis. RESULTS: We observed a dose-dependent increase in cellular content of CD3-zeta chain in Jurkat T cells treated with HYD. Our results suggest that HYD may result in T cells dysfunction different from this observed in idiopathic SLE T cells. CONCLUSIONS: This difference may partially explain distinct disease course in patients with HYD induced and idiopathic SLE. PMID- 17357304 TI - Flow cytometric analysis of CD4+ T cell receptor zeta chain deficiency in patients with systemic lupus erythematosus. AB - PURPOSE: It has been reported that a dysfunction of T lymphocytes can be responsible for alteration in immune system in patients with systemic lupus erythematosus (SLE). MATERIAL AND METHODS: Using flow cytometric analysis, we determined the abnormalities of T cell receptor zeta (TCR zeta) chain contents in CD4+ T cells of SLE patients. RESULTS: We observed a decrease in mean fluorescence intensity of TCR zeta in CD4+ T cells of patients with SLE. The multiple analysis did not show a correlation between gender, age, disease specific manifestation, treatment, duration and TCR zeta mean fluorescence intensity in CD4+ T cells. CONCLUSIONS: High prevalence of TCR zeta chain deficiency in CD4+ T cells confirms the significance of this signaling molecule in SLE pathogenesis. PMID- 17357305 TI - Photodynamic diagnosis (PDD) using 5-aminolevulinic acid-supplemented cultures of human endometrial epithelial cells. AB - PURPOSE: The studies were aimed at monitoring 5-aminolevulinic acid (5-ALA) dependent accumulation of endogenous protoporphyrin IX (PpIX) in epithelial cells originating from normal endometrium or endometriotic foci, as related to steroid treatment. MATERIAL AND METHODS: Epithelial cells were cultured in presence of estradiol-17 beta (E2) and progesterone (P) in concentrations typical for the follicular stage (E2 alone, 220 pg/ml) or the luteal stage (E2 100 pg/ml and P 2 ng/ml) or in presence of progesterone alone (2 ng/ml) for a period of 24, 48 or 72 h. Effect of 5-ALA concentration on the accumulation of PpIX was defined in the cells incubated with 2.0 mmol/l 5-ALA for 2 h. PpIX fluorescence was detected using a confocal microscope. RESULTS: After hormonal stimulation, intensity of PpIX-specific fluorescence was only slightly increased in epithelial cells originating from normal endometrium. Cultures of epithelial cells from endometriosis foci showed higher concentration of PpIX than did the cells originating from normal endometrium. The highest peak of PpIX fluorescence was noted in epithelial endometriotic cells after 48h incubation with progesterone. CONCLUSIONS: The data on PpIX accumulation in epithelial cells in the presence of estradiol-17 beta or progesterone may provide indications as to the menstrual cycle phase(s) in which photodynamic therapy for endometriosis should be performed. It is concluded that hormonal condition of female body must be taken into account for diagnosis and treatment of endometriosis. PMID- 17357306 TI - Immature reticulocyte fraction (IRF)--an universal marker of hemopoiesis in children with cancer? AB - PURPOSE: Anemia is one of the most frequent side effects of anticancer treatment, it is also caused by disease itself. Reliable laboratory tests indicating hematological recovery after chemo- and radiotherapy are needed. Effective erythropoiesis can be monitored by quantitative measurement of reticulocytes. The amount of RNA in these cells can be assessed with flow cytometry and divided into low- (LFR), middle- (MFR) and high-fluorescence reticulocytes (HFR). This distribution is correlated with their maturation. MATERIAL AND METHODS: The aim of our study was to find the most sensitive indicator of anaemia among reticulocyte subpopulations assesed by flow cytometry in children with cancer. 46 children with different neoplasmatic diseases were enrolled into the study. RESULTS: 1) we did not find any differences between control and examined group at the time of diagnosis except for IRF, which was higher in examined group (p = 0.001); 2) IRF was lower already 2-4 days after end of chemotherapy (p = 0.03), and rised before next regimen (p = 0.0006). CONCLUSIONS: In conclusion we showed that IRF is not only the first sign of hematologic recovery but also very strong indicator of postchemotherapy aplasia in children with cancer and may serve as a additional parameter of bone marrow function in clinical studies. PMID- 17357307 TI - Protecting the peritoneal membrane in dialyzed patients. AB - This review paper describes methods of protecting the peritoneal membrane in uremic patients chronically treated with peritoneal dialysis. Possible interventions involved in protection of the peritoneum aim at reducing peritoneal exposure to glucose, glucose degradation products and lactate; preventing or diminishing harmful effects of dialysis solutions; decreasing infection rate, especially peritonitis, and its consequences. Techniques reducing peritoneal exposure to bioincompatible solutions include peritoneal resting, replacing some glucose exchanges with amino acid-based, icodextrin-based or glycerol-based dialysis solution, using bicarbonate or pyruvate as a buffer, and administering solutions with low content of glucose degradation products. Preventing or diminishing harmful effects of dialysis solutions includes interventions with drugs, especially those given intraperitoneally. Decreasing local and systemic infection rate is also very or even the most important in maintaining relatively unchanged peritoneal membrane histology and function. PMID- 17357308 TI - Realization of International Healthy Hearing Program in Poland--hearing evaluation in participants of Special Olympics. AB - PURPOSE: International Healthy Hearing Program developed by International Special Olympics in Washington DC performs hearing screening during athletics competitions of athletes with mental retardation. The aim of this study was to introduce hearing screening performed according to Special Olympics Incorporated (SOI) Healthy Athletes Program. MATERIAL AND METHODS: The study was performed in Polish participans of Special Olympics during Summer National Special Olympics Game in Olsztyn in 2005 and Winter National Special Olympics Game in Bialystok in 2004. HH evaluation was divided into 4 screening sequences: otoscopy, otoacoustic emission (DPOAE), tympanometry and pure-tone audiometry. During athletics competitions 208 Polish participants were examined. RESULTS: Of the total 208 athletes screened: 156 passed OAE (75%), 42 passed pure tone screening at 25 dB HL (20.2%), and 5 more passed the pure tone threshold test (2.4%). It means total of 203 passing hearing testing (97.6%). Hearing impairments were detected in 4.8% athletes and 2.4% of athletes needed hearing aids. CONCLUSIONS: HH Program provided a more precise analysis of hearing in the group of athletes with mental retardation and a recognition of subjects who need audiological care. PMID- 17357309 TI - Tumor front grading in prediction of survival and lymph node metastases in patients with laryngeal carcinoma. AB - PURPOSE: Despite innumerous both therapeutic and histopathologic studies that have been performed no morphologic markers are currently available in order to predict the outcome in patients with laryngeal cancer. According to the recent reports nowadays tumor front grading (TFG) is one of the most reliable methods of estimation of the progress of the changes in the peripheral part of tumor and it seems to be one of the technics, which is able to assess the dynamics of the tumor growth quite precisely. In this sudy it was presented direct relation between morphological features of tumor front and survival. MATERIAL AND METHODS: The authors have analysed 120 cases of patients who were operated on the laryngeal squamous cell carcinoma in ENT Department Medical University of Lodz between 1995-2000. Features of the morphologic tumor front grading was performed on H&E-stained sections in the peripheral parts of a tumor. Dependence on tumor grade G, tumor size T, lymph node metastases and survival were analysed. RESULTS: Our study showed that feature such as TFG is very useful in prediction of survival in patients with laryngeal squamous cell carcinoma in comparison to the histological differentiation degree. The statistical analysis showed no significant correlation between TFG score and tumor size T, nodal status N and G feature. CONCLUSIONS: The presented study emphasizes that TFG might influence decisions regarding therapeutic management and could eventually lead to more appropriate and individualized therapy. It is necessary to extend the traditional histopathological diagnosis by TFG, which assesses the dynamics of the malignant process and it seems to be a good prognostic method in prediction of survival of patients with squamous cell carcinoma. PMID- 17357310 TI - Activity of coagulation and fibrinolytic system components in the vein thrombus. AB - PURPOSE: Behaviour of the vein thrombus is determined by the activity ratio of coagulation factors to factors of fibrinolytic system. The aim of the study is to evaluate activity of some coagulation and fibrinolytic factors in the vein thrombus. MATERIAL AND METHODS: The activity of platelets aggregating factors, tissue factor, thrombin, antithrombins, antiheparin factors, plasminogen activators, plasmin (plasminogen) and antiplasmins of the vein thrombus homogenate was determined using coagulative, fibrinolytic and caseinolytic tests. Retracted blood clot was a compared material. RESULTS: Tissue factor activity in the vein thrombus was above twofold higher and antiheparin activity was nearly twice higher in comparison to the blood clot. The vein thrombus contains also active thrombin. Plasminogen activators activity in the vein thrombus was twofold higher and activity of plasmin (plasminogen) was threefold higher than in the blood clot. High activity of the tissue factor, substances neutralizing heparin and presence of thrombin intensify the thrombus enlargement. However, the thrombotic tendency may be balanced by a high activity of plasminogen activators and high activity of plasmin (plasminogen). CONCLUSIONS: 1) Vein thrombus is characterized by high activity of tissue factor, presence of active thrombin and high antiheparin activity. 2) High coagulative potential of vein thrombus is balanced to a certain grade by high fibrinolytic potential: high activity of plasminogen activators and high activity of plasmin (plasminogen), as well as absence of antiplasmins activity. PMID- 17357311 TI - The use of parotid gland activity analysis in patients with gastro-esophageal reflux disease (GERD) and bulimia nervosa. AB - PURPOSE: In patients with vomiting or reflux episodes, specific pathognomic signs may occur in the oral cavity. The significance of salivary gland activity in this type of disorder is a matter of dispute. The purpose of this study was to evaluate the parotid gland activity of patients with bulimic type eating disorder (group B) compared with patients affected by gastro-esophageal reflux (GERD) (group A) and healthy control subjects (group C). MATERIAL AND METHODS: Parotid saliva was collected during the clinical examination by means of a modified Lashley cap under unstimulated and stimulated conditions and the flow rate was determined. The concentrations of Na+, K+, Ca+ (mmol/l) were determined by a colorimetric photometry method (Effox 5053, Eppendorf, Germany). Buffering capacity as a concentration of bicarbonates (mmol/l) and the pH, were measured by an automatic ion-selective electrode (ABL TM 520, Radiometer, Denmark). For the statistical analyses Kruskal Wallis one way ANOVA on Ranks with Dunn's method all pairwise multiple comparisons procedures were used with significance set at p < or = 0.05. RESULTS: The results showed that the flow rates in the subjects in group A and B were significantly lower than in the controls. There were also significant differences in the concentration of sodium, with the lowest level in group B, and calcium where the highest level occurred in group A. CONCLUSIONS: Since patients may deny frequent vomiting (bulimia) or are unaware of the reflux (GERD) the changes in electrolyte levels revealed by this study appear to be of use in the diagnosis of these conditions. PMID- 17357312 TI - Plasma fibrinogen concentration in pediatric patients treated with an elimination diet based on soy proteins and casein hydrolyzate. AB - PURPOSE: Fibrinogen is one of the most discussed new risk factors of atherosclerosis. The aim of the study was to assess the relationship between fibrinogen concentration and classic risk markers of atherosclerosis in a group of children aged from 2 to 6 with or without a family history of circulatory system diseases (FHCAD) (American Academy of Pediatrics--AAP criteria). The study also considered the impact of allergies/food intolerance treatment with elimination diets on the concentration of atherosclerosis markers specially fibrinogen. MATERIAL AND METHODS: INCLUSION CRITERIA: a) family history of early occurrence of circulatory system diseases (FHCAD+) according to AAP standards; b) the type and duration of elimination diet continued in infancy and early childhood. 134 of 388 children were included in the investigation. RESULTS: The analysis of data relating to the so-called classic biochemical risk factors of atherosclerosis (total cholesterol--TC, HDL, LDL, triglycerides, glucose) did not reveal any differences between the tested groups. It was found that in the FHCAD+ group the concentration of fibrinogen was statistically higher than in the group with a negative family history. It was discovered that the type of elimination diet had no effect on fibrinogen level in the FHCAD+ group. In the group of children with negative family history the concentration of fibrinogen was statistically lower in the group on casein hydrolysate than in children treated with soy formula. CONCLUSIONS: The initial interview in pediatrics should include information on the patient's family history of atherosclerosis. In case of a positive family history, fibrinogen, as one of atherosclerosis risk factors, should be monitored. PMID- 17357313 TI - Empathy in health care providers--validation study of the Polish version of the Jefferson Scale of Empathy. AB - PURPOSE: Empathy as a crucial component of the interpersonal relationship needs to be measured, especially in helping professions. We designed this study to adapt both "Student" ("S") Version and "Health Professionals" ("HP") Version of the Jefferson Scale of Empathy (JSE) to Polish population. MATERIAL AND METHOD: Three instruments were administered to 405 respondents: Polish version of the JSE, Interpersonal Reactivity Index (IRI) measuring four aspects of empathy (i.e. empathic concern, fantasy, personal distress and perspective taking), Emotional Intelligence Scale (EIS). JSE was applied to physicians, nurses and medical, nursing and midwives students in order to calculate reliability coefficient and other psychometric data. In order to assess validity of the scale, the empathy results were correlated with those obtained by respondents on IRI and EIS. RESULTS: Cronbach alpha reliability coefficient for "S" verSION WAS 0.73, for "HP" version - 0.79, whereas for the entire sample was 0.71. Neither significant differences on empathy scores were found between genders nor among five groups of respondents on JSE. Physicians obtained the highest mean of empathy score (M = 113.06), while the lowest was observed in nurses (M = 110.12). Empathy results on JSE correlated significantly with "empathic concern" (r = 0.25, p < 0.01) and with "perspective taking" (r = 0.26, p < 0.01). Also significant correlation was found between empathy and emotional intelligence. CONCLUSIONS: Despite the lower (but acceptable) reliability coefficient of the Polish JSE in comparison with the original version, the scale proved to be very useful instrument evaluating empathy in health care professionals and students. Further research is needed to identify factors that contribute to changes in psychometric data of the scale. PMID- 17357314 TI - Improvement in the accessibility and organization of services of family physicians in a small town in Poland: a comparison of patient opinions between 1998 and 2002. AB - PURPOSE: The institution of a family physician was introduced in Poland to improve organization and quality of primary health care. Thus, it seems important to find out how the time factor (4 years) and the organizational changes that took place during that time have affected patients' views on primary health service accessibility. The aim of the study was to compare patients' opinions on selected aspects of the access and organization of health care provided by family physicians between the years 1998 and 2002. MATERIAL AND METHODS: Two independent surveys conducted in 1998 and 2002 using face-to-face interviews with structured questionnaires. The study was carried out in a small town in Poland. The study group consisted of two samples of patients randomly selected. Altogether 1000 interviews were obtained in survey I (1998) and 1000 from another sample in survey II (2002). RESULTS: The surveys carried out at a 4-year interval showed that the accessibility of family physician services improved between 1998 and 2002. This was reflected by: more common use of registration by phone and better overall evaluation of the registration system, shorter time spent in the waiting room to see a family physician, making an appointment for a definite hour, better opinion of the visit duration and more frequent use of phone consultations. CONCLUSIONS: The results our study show that primary health care reform in Poland has a positive impact on the patients' opinions about access and organization of services of family physicians. PMID- 17357315 TI - Differentiation of IgE-dependent and IgE-independent reactions in children with bronchial asthma on the basis of TOP CAST Paediatric Allergen Mix test. AB - PURPOSE: TOP CAST Paediatric Allergen Mix test is a new cellular in vitro test based on evaluation of leukotrienes synthesised by basophils under the influence of specific allergens. The aim of the study was evaluation of applicability of this test as screening examination in diagnosis of atopic asthma in children. MATERIAL AND METHODS: The study was carried out on a group of 30 children (56.7% boys and 43.3% girls) aged 6-15 yrs (mean age 8 years and 9 months, SD = 2.1) with diagnosed bronchial asthma. In children qualified for the study clinical symptoms, subject examination as well as functional examination of the respiratory system (obturation with positive reversibility test) confirmed the disease. All the children had skin prick tests performed with the most popular aero- and troph-allergens, which results were expressed (+) according to the Skandinavian scale. In 15 cases asthma had atopic origin: in 11 children--mites were responsible for the contraction of bronchi, in 3 cases--tree-pollens allergens and in 1 case--grass pollens. In 15 next cases non-atopic asthma was diagnosed. The control group consisted of 10 children without clinical manifestations of asthma and negative results of the above tests. Test TOP CAST Paediatric Allergen Mix with mixture of 21 inhalatory and food allergens was performed according to the producer's procedure. RESULTS: Statistically significant differences of the values of released leukotrienes were noted at allergen concentration of both 100 ng/ml and 10 ng/ml in children with diagnosed atopic asthma compared to those with non-atopic asthma and control group. The sensitivity of TOP CAST Paediatric Allergen Mix test was 80% at both allergen concentrations while the specificity was higher (90%) at the lower concentration. There was also correlation between the number of released leukotriens and IgEc in the examined group of children, however, no statistically significant differences were observed between the concentration of the released leukotrienes and the size of the wheal and the number of positive skin prick tests. CONCLUSIONS: 1. TOP CAST Paediatric Allergen Mix test is a good screening method in differentiation of atopic and non-atopic background of bronchial asthma in children. 2. At the present evaluation stage of this test, it may be applied as complementation of routine tests in allergological practice. PMID- 17357316 TI - Functioning of primary health care in opinion of managers of primary health care units. AB - PURPOSE: The aim of the research is to get to know opinions of primary health care managers concerning working of primary health care and concerning quality of medical services offered by family doctors out-patient clinics. MATERIAL AND METHODS: The research among managers of primary health care units took place in all out-patient clinics in Lublin province. Research instrument was survey questionnaire of authors own construction. Results were statistically analyzed. RESULT: From 460 surveys sent, 108 questionnaires were accepted to analysis. Majority of managers of out-patient clinics of primary health care is satisfied with the way and the quality of work of employed staff. In opinion of 71.3% of managers access to family doctor services is very good. Availability of primary health care services is better estimated by managers of not public units. The occupied local provide comfortable work for the staff in opinion of 78.5% of surveyed managers of out-patient clinics. Managers estimate the level of their services as very good (37.96%) and good (37.96%) comparing to other such a subjects present in the market. Internal program of improving quality is run in 22% of out-patient clinics, which were investigated. CONCLUSIONS: Managers of primary health care units assess the quality of their services as good and very good. They estimate positively the comfort and politeness in serving patients as well as technical status of equipment and the lodging. They assess availability of their services as very good. Large group of managers of family doctors practices recognizes neighborhood practices as a competitors. PMID- 17357317 TI - Alternative therapies in antibiotic-resistant infection. AB - CASE REPORT: A 24-year-old woman suffering from post-influenza otitis media infection was initially treated with several series of a steroid (Elocon) and a combination of steroids and antibiotics (Atecortin, Dicortineff) without significant medical benefit. The isolated bacterial strains were identified as Staphylococcus homis and Staphylococcus epidermidis. Specific phage therapy applied sequentially over a period of three weeks resulted only in a partial reduction in inflammation and limited improvement in overall health condition. Oral application of lactoferrin (LF; 50-mg daily oral doses for seven days with two-week intervals) led to a complete clearance of both bacterial strains and full recovery of the patient. The recovery was associated with increased myelopoiesis and a sustained elevation of serum endogenous LF. In conclusion, specific bacteriophage therapy combined with the administration of lactoferrin proved to be effective in the treatment of antibiotic-resistant external ear infection. PMID- 17357318 TI - Ultrastructural study of the submandibular gland of the rat after 6-month exposure to cadmium and zinc in drinking water. AB - PURPOSE: Cadmium toxicity in the exposure of the general, professional and cigarette smoking populations has been well known. From the dental point of view, it is important to find out whether and how separate and joint exposures to cadmium and zinc affect the structure and function of the submandibular gland, which is the major saliva-releasing gland. Cadmium, a particularly active xenobiotic, damages cellular metabolism at the level of various enzymatic systems of the cell, which may disturb functioning of the salivary glands. Mutual interactions of cadmium and zinc suggest a protective role of zinc through the induction of metallothionein which inactivates cadmium effect. MATERIAL AND METHODS: The aim of the study was to assess the ultrastructural picture of chosen cell organelles of the submandibular salivary gland of the rat exposed to cadmium and zinc. The study used 90 male Wistar rats, of the initial b.w. 150-180 g. The animals were exposed to cadmium and/or zinc for 6 months. Cadmium was received in aqueous solutions of cadmium chloride with drinking water at a concentration of 5 mg Cd/dm3 or 50 mg Cd/dm3. Zinc was also given in aqueous solutions of zinc chloride ad libitum at concentrations of 30 mg Zn/dm3 and 60 mg Zn/dm3. RESULTS: The ultrastructural changes in the mucous and serous cells of the submandibular salivary gland were most pronounced at cadmium concentration of 50 mg Cd/dm3 and were mainly observed in the cell nucleus, Golgi Apparatus and secretory granules of the salivary gland cells. CONCLUSIONS: 1. Exposure to cadmium induces ultrastructural changes in the submandibular gland, which are dose and time of exposure. 2. Exposure to zinc did not affect significantly the ultrastructural picture of cells of the submandibular gland. 3. Zinc administered together with cadmium reduces the intensity of ultrastructural changes in the submandibular gland. PMID- 17357319 TI - Ureaplasma urealyticum and Mycoplasma hominis infection in women with urogenital diseases. AB - PURPOSE: The aim of the study was to assess the incidence of Ureaplasma urealyticum (U. urealyticum) and Mycoplasma hominis (M. hominis) infection in women with urogenital diseases. MATERIAL AND METHODS: M. hominis and U. urealyticum was assessed in 541 women from gynaecological and STD outpatient clinics, aged 18-55 years. A Mycoplasma IST 2 kit was used for biochemical determination of mycoplasmal infections (BioMerieux). Additionally, 248 of patients were examined for Chlamydia trachomatis (C. trachomatis), Trichomonas vaginalis (T. vaginalis) and Candida albicans (C. albicans) infection. C. trachomatis was detected by direct immunofluorescence method. The standard culture methods (Biomed) were applied to detect T. vaginalis and C. albicans. RESULTS: U. urealyticum was detected in 161 (29.8%), and M. hominis in 20 (3.7%) women. U. urealyticum infection alone was observed in 37/79 (46.8%), and 1/8 (12.5%) patient had only M. hominis infection. The U. urealyticum infection showed most frequent coexistence with C. albicans (29.1%), and less frequent with C. trachomatis (13.9%) and M. hominis infection (10.1%). The highest percentage of mycoplasma-positive cultures was found in patients of STD clinic and in infertile women. In patients with ureaplasmal infection only the most common clinical symptom was vaginal discharge and vulval/vaginal irritation. In 8.1% of the women, the course of U urealyticum infection was asymptomatic. CONCLUSIONS: The incidence rate of genitourinary infections due to U urealyticum was significantly higher as compared to M. hominis infection. Sexual mycoplasmal infections were most frequently reported in the group of patients of STD clinic and correlated with age and sexual activity. PMID- 17357320 TI - Mycoplasma hominis and Ureaplasma urealyticum infections in male urethritis and its complications. AB - PURPOSE: The aim of this study was to estimate the incidence of M. hominis and U. urealyticum infections among men with urethritis and its complications. MATERIAL AND METHODS: Material for analysis were urethral swabs and EPS. Mycoplasma IST 2 kit was applied to diagnose mycoplasmal infections. All patients were additionaly tested for C. trachomatis, C. albicans and T. vaginalis and Gram stain specimens were obtained to identify the presence of PMN. RESULTS: U. urealyticum was detected in 57/390 (14.6%), and M. hominis in 4/390 (1%) men. Exclusive U. urealyticum infection was found in 45 (11.5%) men, and only 2 patients had exclusive M. hominis infection. U. urealyticum infection the most frequently coexisted with C. trachomatis--5 (8.8%), next with C. albicans--4 (7%) and M. hominis--2 (3.5%) infections. Mycoplasmal infections were the most frequently found in patients aged 30 to 39 (35.1%) diagnosed with epididymitis (29.2%). The most commonly reported symptom was dysuria. CONCLUSIONS: U. urealyticum is the common pathogen among men with urethritis and its complications. The most common symptoms in U urealyticum patients were: dysuria, hypogastric pains and urethrorrhoea, however, clinical symptoms are not frequently observed. PMID- 17357321 TI - Orbital pseudotumor caused by a foreign body--a case report. AB - The case of a patient with a foreign body in the orbit is presented. The presence of this foreign body induced an aggressively expanding pseudotumor, infiltrating the eyelids, orbital muscles and the sclera. The process of diagnosis, management and the results of treatment are described. This case is noteworthy because of the atypical course of the disease in a patient with a foreign body following ocular injury. PMID- 17357322 TI - Met-enkephalin in the liver as a marker of hepatocellular damage in chronic viral hepatitis type B and C. AB - PURPOSE: The aim of the study was to assess the liver Met-enkephalin concentration in chronic viral hepatitis type B and C as well as in liver cirrhosis in order to estimate the role of opioid system in pathogenesis of liver disease. MATERIAL AND METHODS: The concentration of Met-enkephalin was examined in liver tissue of 103 consecutive patients with chronic hepatitis type B and C. Control group consisted of uninfected patients. Met-enkephalin concentration was analyzed in relation to the degree of hepatic necroinflammatory activity and the extent of fibrosis estimated by histopathological examination of liver bioptates and compared to such parameters as age, sex and concomitant diseases. RESULTS: Significant differences in Met-enkephalin concentration were found between cases with advanced fibrosis (stage 3 and 4 acc. to Batts and Ludwig classification) and cases with fibrosis classified as stage 2 (p < 0.05). Met-enkephalin concentration was higher in HCV infected patients in comparison to HBV infected patients (p < 0.05) and uninfected controls (0.05 < p < 0.1). There wasn't found any correlation between Met-enkephalin level and necroinflammatory activity in the liver, age, sex and concomitant diseases. CONCLUSIONS: Met-enkephalin concentration measurement in the liver tissue seams to be a useful method for differentiation of stage 2 from stages 3 and 4 of severe liver fibrosis. There is increased concentration of Met-enkephalin in liver tissue in HCV infected patients in comparison to HBV infected or uninfected individuals. The degree of necroinflammatory activity in the liver as well as sex and age of patients with chronic hepatitis do not correlate with changes in opioid system. PMID- 17357323 TI - Serum homocysteine, folate, vitamin B12 and total antioxidant status in vegetarian children. AB - PURPOSE: The results of several studies point to the positive role of vegetarian diets in reducing the risk of diabetes, some cancers and cardiovascular diseases. However, exclusion of animal products in vegetarian diets may affect the cobalamin status and cause an elevation of the plasma homocysteine level. The aim of this study was to assess the effect of vegetarian diets on serum concentrations of homocysteine, folate, vitamin B12 and total antioxidant status (TAS) in children. MATERIAL AND METHODS: The study included 32 vegetarians (including 5 vegans), age 2-10 years. Dietary constituents were analyzed using a local nutritional programme. Serum homocysteine, folate and vitamin B12 were determined with fluorescence and chemiluminescence immunoassays. The concentration of TAS was measured by a colorimetric method. RESULTS: Average daily energy intake and the percentage of energy from protein, fat and carbohydrates in the diets of the studied children were just above or similar to the recommended amounts. It could be shown that vegetarian diets contain high concentrations of folate. In vegan diets it even exceeds the recommended dietary allowance. Mean daily intake of vitamin B12 in the studied diets was adequate but in vegans was below the recommended range. The serum concentrations of homocysteine, folate, vitamin B12 and TAS in vegetarian children remained within the physiological range. CONCLUSIONS: The presented data indicate that vegetarian children, contrary to adults, have enough vitamin B12 in their diet (excluding vegans) and normal serum concentrations of homocysteine, folate and vitamin B12. Therefore, in order to prevent deficiencies in the future, close monitoring of vegetarian children (especially on a vegan diet) is important to make sure that they receive adequate quantities of nutrients needed for healthy growth. PMID- 17357324 TI - Osteoprotegerin and C-telopeptide of type I collagen in Polish healthy children and adolescents. AB - PURPOSE: Most metabolic bone diseases are characterized by a disturbances in bone resorption, therefore biochemical markers concerning this process are of special interest. Recently, the novel cytokine osteoprotegerin (OPG), belonging to the tumor necrosis factor receptor family has been established as an endogenous inhibitor of osteoclastogenesis and resorption process. In addition serum C telopeptide of type I collagen (s-CTX) is one of the resorption markers released into circulation as a result of the osteoclast mediated degradation of type I collagen. However, a clinical application of OPG and s-CTX in children may be difficult by less information of suitable reference data in relation to age, race and sex. The aim of our study was to invastigate serum concentrations of both markers in polish healthy children and adolescents. MATERIAL AND METHODS: We examined 102 healthy children and adolescents in 6-24 years of age, divided on prepubertal, pubertal and postpubertal groups. OPG and s-CTX were determined by ELISA kits from Biomedica (Austria) and Osteometer (Denmark) respectively. RESULTS: The highest mean values of OPG were in prepubertal girls (4.64 +/- 0.57 pmol/L) and boys (4.28 +/- 0.86 pmol/L). Next, in older children and adolescents gradually decreased of OPG concentration was observed. We also obtained the decreased of s-CTX concentration in studied children except these in pubertal period. Generally, we obtained significant positive correlation between OPG and s CTX in all observed groups (n = 102, r = 0.653; p < 0.0001). CONCLUSIONS: We report the age-related decrease in circulating endogenous OPG during childhood and adolescence. Serum OPG concentration in postpubertal period may be similar to those presented in young adults. Prospective studies are needed to investigate the influence of OPG on bone metabolism in children. PMID- 17357325 TI - Event-related cerebral potentials for the diagnosis of subclinical hepatic encephalopathy in patients with liver cirrhosis. AB - PURPOSE: Subclinical hepatic encephalopathy (SHE) seems to be a common problem in liver cirrhosis, however, studies assessing the pathogenesis of this disease remain unclear. Currently no gold standard exists for the diagnosis of this complex neuropsychiatric syndrome. The present study was undertaken firstly to examine the diagnostic usefulness of auditory event-related cerebral potentials (ERPs) in the detection of SHE, and secondly to compare it with that of the most validated psychometric test. MATERIAL AND METHODS: 22 patients with liver cirrhosis without overt hepatic encephalopathy and 28 healthy controls were studied, using auditory ERPs. In addition they underwent a battery of neuropsychological and laboratory tests. RESULTS: P300 latency analysis turned out that cirrhotics patients had significantly longer P300 latency than controls. The only neuropsychological test showing significant difference between clinical and control group was the similarities subtest of WAIS-R. CONCLUSIONS: The results of the present study suggest that ERPs are more sensitive method than psychometric tests in detecting early changes in the brain function of patients with cirrhosis and for this reason this neurophysiological method should be applied in clinical practice. PMID- 17357326 TI - Influence of nutritional treatment on the postoperative course in patients with gastric cancer. AB - PURPOSE: Malnutrition occurs in ca. 60% of all patients with gastric cancer. The obligatory standard for a curative radical oncological procedure is gastrectomy inclusive of regional lymph nodes. Nutritional treatment is expected to decrease possibilities of postoperative complications in patients subjected to curative surgery. The study is aimed at comparing treatment results in patients with gastric cancer subjected to radical surgery, nutritional and non-nutritional treatment respectively. MATERIAL AND METHODS: The study included 176 patients qualified for curative surgery of a total or subtotal gastrectomy. Analysed were 2 groups of patients: group I--not subjected to nutritional treatment, group II- subjected to nutritional treatment, both in the circumoperative period. The groups were compared in respect to: 1) age, 2) sex, 3) nutritional condition, 4) degree of clinical cancer development, 5) histopathological cancer type, 6) kind of surgical procedure performed, 7) antibiotic and antithrombotic prevention. All complications observed in the patients were divided into four kinds: surgical of a high or low risk and general of a high or low risk. RESULTS: Given the above mentioned estimation parameters, no statistically significant differences between both groups were recorded. Of 176 patients, 27% showed surgical complications and 40% had general complications. No difference (p = 0.60) in the incidence of a high and low risk surgical complications between groups I and II in the circumoperative period was observed, a significant difference (p = 0.03) was recorded in the incidence of general complications. Low risk general complications (respiratory infections) were shown to occur significantly more often (p = 0.005) in patients receiving either parenteral or enteral nutrition after surgery. CONCLUSIONS: A significant part of the patients with a medium degree and a medium to heavy degree of malnutrition subjected to a curative gastrectomy can pass through the postoperative period without using either parenteral or enteral nutrition and with no violations of all the other principles of the postoperative procedure as well as without provoking any significant increase of surgical complications. In case surgical complications should occur and delay resuming natural feeding, it is necessary that parenteral and/or enteral nutritional treatment be undertaken according to clinical circumstances and condition of the patient concerned; such proceedings increase chances of cure. PMID- 17357328 TI - Body posture in women after mastectomy and its changes as a result of rehabilitation. AB - PURPOSE: The aim of the study is: 1) to analyse selected features of body posture in women after mastectomy, 2) to compare them with body posture of healthy women, 3) to determine the effect of rehabilitation physical exercises on the changes in body posture in women after mastectomy. MATERIAL AND METHODS: The research material consisted of 85 women after mastectomy examined once, including 40 of them who were additionally examined twice at six-monthly intervals. Moreover, a group of 20 women was isolated who regularly attended rehabilitation classes for a period of one year in question. A comparative group was a group of 85 healthy women. The examinations were performed using photogrametric assessment of body posture. RESULTS: Distinct adverse changes in body posture of women after mastectomy in comparison with healthy women were found, manifested mainly in asymmetry of trunk and shoulder girdle and greater forward leaning of the trunk. Significant relationship was indicated between the operation of mastectomy and the asymmetry of position of scapulas. CONCLUSIONS: When comparing the changes in the features of body posture in the group of women who exercised regularly with other women for the period of one year it was found that a positive effect of regular rehabilitation was keeping the angle of body inclination on the same level and improvement in trunk symmetry, position of scapulas and shoulder girdle. PMID- 17357327 TI - Anaplasma phagocytophilum in Ixodes ricinus ticks and human granulocytic anaplasmosis seroprevalence among forestry rangers in Bialystok region. AB - PURPOSE: Human granulocytic anaplasmosis, former ehrlichiosis, is a tick-borne zoonosis of increasing recognition. The aim of the study was: 1) to assess the prevalence of Anaplasma phagocytophilum infection in Ixodes ricinus ticks collected in recreational forests in Bialystok vicinity, the capital of podlaskie voivodship; 2) to evaluate the prevalence of IgG and IgM antibodies to A. phagocytophilum among forestry rangers from the same region. RESULTS: Of the 372 ticks examined, 54 (14.5%) yield the positive PCR reaction. The highest prevalence was detected in females, up to 27.8% (37/133), almost one third lower in males--9.2% (13/142), followed by nymphs--4.1% (4/97). Human seropositivity study revealed IgG antibodies against A. phagocytophilum in 9 out of 231 individuals (3.9%). No IgM antibodies were found. Sixty-seven individuals 67/231 (29%) reported erythema migrans. IgM anti-Borrelia burgdorferi antibodies were detected in 32 out of 121 (26.4%) persons tested, IgG--in 43 out of 231 (18.6%). CONCLUSIONS: The data obtained show relatively low A. phagocytophilum seroreactivity among professionally exposed to tick group of forestry workers despite high A. phagocytophilum infection level in the competent vector--I. ricinus ticks. PMID- 17357329 TI - The comparison of effect of catechins and green tea extract on oxidative modification of LDL in vitro. AB - PURPOSE: Green tea due to its content of catechins reveals strong antioxidative activity, which is manifested among others by its ability to inhibit free radical generation, scavenge free radicals as well as chelate transition metal ions that catalyse free radical reactions. The influence of green tea extract, epicatechin (EC), epicatechin galate (ECG) as well as epigallocatechin galate (EGCG) on oxidative modifications of LDL of human blood serum has been examined in the present study. MATERIALS AND METHODS: This influence has been evaluated by measurement of the concentration of first products of lipid peroxidation- conjugated dienes and lipid hydroperoxides as well as by determining tryptophan and dityrosine content-- the markers of protein oxidative modification. RESULTS: Catechins and green tea abilities to protect lipophilic antioxidant--alpha tocopherol against oxidation have been also examined. The results reveal that peroxidation of LDL is markedly prevented by green tea extract and in a slightly weaker way by catechins (EGCG in particular), which is manifested by a decrease in concentration of conjugated dienes, lipid hydroperoxides, MDA, dityrosine and by an increase in tryptophan content. Both green tea as well as catechins (EGCG in particular) have been also revealed to prevent decrease in concentration of alpha-tocopherol in oxidating conditions. CONCLUSIONS: It can be assumed that green tea and to a lesser degree catechins, protecting the basic antioxidant of LDL-alpha-tocopherol, prevent oxidative modification of LDL. PMID- 17357330 TI - Changes in platelet CD 62P expression and soluble P-selectin concentration in surgically treated colorectal carcinoma. AB - PURPOSE: The aim of the present study was to assess the effect of tumor advancement and surgery treatment on P-selectin expression (CD 62P), level of sP selectin and platelet count. MATERIAL AND METHODS: The study involved 27 colorectal cancer patients (CRC). They were divided into two groups: group B1--18 patients (T2-3N0M0) and group B2--9 patients (T2-4N+M0). In CRC patients the blood was collected three times: 1) before surgery (A0), 2) 3 days after surgery and 3) 12 days after surgery. RESULTS: The results obtained showed that CD 62P expression in CRC patients was twice higher (5.36%) than in control (2.58%) (p < 0.001). The level of sP-selectin concentration in both groups (B1--74.22 ng/mL and B2--70.33 ng/mL) was significantly higher than in control (46.01 ng/mL) (p < 0.001). There was no significant differences in CD 62P expression, plasma sP selectin concentration and in PLT count between group B1 and B2. Three days after surgery in both groups of patients we observed decreased CD 62P expression and sP selectin level compared to the results before surgery (p < 0.05). Twelve days after surgery we found an increase in the CD 62P-positive platelets and sP selectin in group B1 and B2. We found positive correlation between plasma sP selectin concentration and PLT count in CRC. CONCLUSIONS: In the current study on colorectal cancer we observed platelet hyperactivation, irrespective of tumor clinical advancement. Surgical procedure, in the early period following radical tumor resection, does not totally eliminate platelet activation in vivo. PMID- 17357331 TI - Anemia treatment with darbepoetin alpha in pregnant female with chronic renal failure: report of two cases. AB - Pregnancy is a rare finding in females with CRF. It is well known that in these cases pregnancy worsens the renal function and accelerates the beginning of dialysis therapy. Pregnancies in uremic females are complicated by a worsening of anemia as well as hypertension, fluid imbalance, electrolyte difficulties, malnutrition, polyhydramnios and preterm labor or sudden intrauterine death. The use of erythropoiesis stimulating agents (ESA) allows a better hematocrit control. Data concerning anemia treatment in pregnants with CRF and data regarding the use of ESA in these patients is scarce. We report two cases of anemia treatment with darbepoetin alpha in pregnant women with CRF in predialysis period and during the hemodialysis therapy. Both patients during the darbepoetin treatment did not require any blood transfusions and at 32nd and 37th weeks of pregnancy delivered healthy infants. The high darbepoetin doses did not cause any side effects, were well tolerated and safe for both gravida and fetus. The effective anemia treatment in pregnants with CRF improves the prognosis for a successful pregnancy. PMID- 17357332 TI - Thrombomodulin in human gestational tissues: placenta, fetal membranes and myometrium. AB - PURPOSE: In intervillous space, thrombomodulin (TM) can be a key component of the protein C anticoagulant pathway that controls the balance between coagulation and anticoagulation/ /fibrinolysis via activation of protein C (APC). In our working hypothesis we assume that not only TM from the placenta, but also TM from myometrium might be engaged in this protective mechanism. To determine whether this is potentially possible, we decided to measure TM concentration in placenta and myometrium, and also in fetal membranes. MATERIAL AND METHODS: The study group consisted of 35 parturient women who delivered at term by cesarean section. Strips of placenta, fetal membranes and myometrium, as well as venous blood samples were collected during operation. The tissues were homogenized. TM was measured by immunoenzymatic method (ELISA). The concentration of TM antigen in placenta was 18.76 +/- 3.83 ng/mg proteins, in fetal membranes 8.57 +/- 1.64 ng/mg proteins and in myometrium 4.72 +/- 1.93 ng/mg proteins, while in blood plasma it was 0.063 +/- 0.016 ng/mg proteins. CONCLUSIONS: It was shown for the first time that thrombomodulin is present in gestational myometrium and fetal membranes. The results support the hypothesis that not only placental TM, but also myometrial TM can participate in maintaining the fluidity of the blood in utero-placental circulation. PMID- 17357333 TI - Oxidative stress in burnt children. AB - BACKGROUND: One of the effects of burn injury is production of reactive oxygen species increasing general-structural damage. Such a condition is called oxidative stress. The purpose of this research was to find out whether oxidative stress is present in burnt children treated routinely and, if so, in which phase of the disease it is the most severe and how long it persists. MATERIAL AND METHODS: The study was carried out on a group of 84 burnt children. The patients were divided into 2 groups: lightly burnt (LB-N:55) and moderately to severely burnt (SB-N:29). Blood samples were collected based on hospitalization period within the 1st, 2nd, 3rd, 7th and 21st day, respectively, following the injury. Total antioxidative capacity (TAC) in plasma and concentration of lipid peroxidation products (TBARS) in red blood cells were estimated. The test results were compared to control group of 40 healthy children. RESULTS: The research showed a statistically significant decrease in TAC in both groups of burnt children. The TBARS concentration was increased in both groups within the 1st day following burn injury and maintained the high level throughout the research continuation. No statistically significant differences between LB and SB groups were recognized. CONCLUSIONS: The observed changes in the tested parameters are attributable to oxidative stress occurring in burn disease. For this reason, burn -injured children are recommended to receive exogenous antioxidants. PMID- 17357334 TI - Gastroesophageal reflux (GER) in children and adolescents with regard to food intolerance. AB - PURPOSE: The hypothesis put forward in the current study was that food intolerance can be a cause of gastroesophageal reflux (GER) affecting children with this pathology at various age. In order to confirm or exclude this hypothesis, the study objective was to determine the frequency of the cause-and effect relationship between allergy to cow milk proteins and/or other food products and gastroesophageal reflux found in the study group of patients, and to establish diagnostic differentiation guidelines in GER caused by food intolerance, i.e. secondary vs primary GER. MATERIAL AND METHODS: A total of 735 children (428 boys--58.2% and 307 girls--41.8%; mean age x = 41.12 months +/- 25.03) with symptoms suggesting gastroesophageal reflux disease (GERD) were qualified for the study. The diagnostic procedure included a 24 h pH-metry of the oesophagus, which was performed in all the study children. In 703 patients (411 boys--55.9% and 292 girls--39.7%) upper gastrointestinal endoscopy was carried out. Manometric examination of the oesophagus was performed in 232 children (123 boys--16.7% and 109 girls--14.8%). Allergological and immunological tests were done in 170 children with suspected allergy (91 boys--12.4% and 79 girls--10.7%). Contrast radiography of the upper gastrointestinal tract was performed in 78 children with respiratory symptoms (42 boys--5.7% and 36 girls--4.9%). Oral challenge test was used to differentiate primary GER from GER secondary to cow milk proteins intolerance or other food allergy in 138 children (72 boys--9.8% and 66 girls--8.9%). RESULTS: Based on the 24 h pH-metry of the oesophagus and endoscopic examination of the upper gastrointestinal tract, gastroesophageal reflux disease and/or reflux oesophagitis were diagnosed in 138 study subjects (18.8%); mean age x = 23.36 months +/- 22.53. Positive oral food challenge test confirmed pathological GER secondary to cow milk protein allergy/other food hypersensitivity in 62 children (8.4%). CONCLUSION: The current study revealed the existence of the cause-and-effect relationship between allergy to cow milk protein/ /other food products and GER in the study children at various age. PMID- 17357335 TI - Gastroesophageal reflux in children and adolescents. clinical aspects with special respect to food hypersensitivity. AB - PURPOSE: Gastroesophageal reflux (acid GER), primary and secondary, has a wide spectrum of clinical symptoms and occurs at developmental age. The study objective was to elaborate the clinical profile of symptoms and to determine whether there are any differences in clinical manifestations between the two acid GER conditions, i.e. primary and secondary to cow milk allergy and/or other food allergy (CMA/FA). MATERIAL AND METHODS: The study involved 264 children of both genders and at various age, with diverse reflux symptoms from one or many organs and with a positive family history of alimentary tract diseases. Based on preliminary diagnostic tests, the children were divided into groups. In 138 children, pathological acid GER, primary and secondary to CMA/FA, was recognized. RESULTS: The profile of clinical symptoms observed in 264 children with suspected gastroesophageal reflux disease (GERD) was elaborated according to their frequency. Among differentiating symptoms the most common were: vomiting (12.1%), bronchitis (10.9%) and pneumonia (9.6%). In the group of 138 GER children, 32 (23.2%) had monosystemic symptoms, in the other 106 patients (76.8%) many systems were affected. The most frequent reflux symptoms were: in primary GER (group 2)- alimentary tract disorders (28.6%), pneumonia and bronchitis (20.7%) and neurological symptoms with torticollis (7.4%); in secondary GER (group 3)- alimentary tract disorders: vomiting and anxiety/crying (25.2%); pneumonia and bronchitis (19.4%). In 23 children (37%) with secondary GER, typical allergic symptoms were found to coexist. The 138 GER patients underwent allergologic and immunologic tests to confirm the allergic background of symptoms. CONCLUSION: Clinical symptoms caused by the presence of secondary acid GER are non-specific, being identical or similar to those observed in primary acid GER. Allergologic and immunologic tests are useful to confirm or exclude the relationship between GER and CMA/FA in the study children. PMID- 17357336 TI - Optimal maintenance therapy in patients with non-erosive reflux disease reporting mild reflux symptoms--a pilot study. AB - PURPOSE: This pilot study aimed at finding trend for further investigation of the optimal maintenance therapy with lansoprazole in patients with non-erosive reflux disease (NERD) suffering from mild symptoms. MATERIAL AND METHODS: Sixty consecutive patients with diagnosed NERD reporting mild symptoms were included in the study. After successfully finishing a four-week treatment with lansoprazole (30 mg daily), the patients were randomized into three groups administered: 1- lansoprazole 30 mg "on-demand", 2--lansoprazole 15 mg daily, 3--lansoprazole 30 mg in four-week courses during a relapse. The intensity of symptoms was assessed with the Visual Analogue Scale (VAS) at the baseline, as well after 4 weeks, 3, 6 and 12 months of therapy. The general satisfaction of treatment was evaluated with the Verbal Rating Scale (VRS) at the same time. RESULTS: At the baseline, the mean intensity of symptoms assessed by VAS was 2.8 +/- 1.0 points and fell to 0.4 +/- 0.5 points after a 4-week therapy. In Group 1, after 3, 6 and 12 months, it was 0.85 +/- 0.6, 1.0 +/- 0.8 and 1.0 +/- 0.8, in Group 2: 0.65 +/- 0.7, 0.65 +/- 0.7, 0.5 +/- 0.3, and in Group 3: 1.1 +/- 0.6, 1.55 +/- 0.7, 1.65 +/- 0.8 points, respectively. No significant differences were observed between Groups 1 and 2. Intermittent therapy (Group 3) showed a significantly lower efficacy in comparison to other groups (p < 0.05). "On-demand" therapy was 30% cheaper whereas intermittent therapy was 55% cheaper than the most expensive daily treatment. However, general satisfaction of treatment assessed by VRS was non significantly different between any of the groups. CONCLUSIONS: In patients with NERD and mild symptoms, both on-demand and daily treatment models of maintenance therapy showed a similar high efficacy, whereas intermittent therapy was significantly less effective. However, general satisfaction of each treatment options was high and non-significantly different between the groups. Due to a pilot character of this study further investigation based on a larger number of patients is necessary to confirm the clinical value of cheaper models of maintenance therapy which could be then recommended as more cost-effective. PMID- 17357337 TI - Elevated concentration of the chemokine CCL3 (MIP-1alpha) in cerebrospinal fluid and serum of patients with tick borne encephalitis. AB - PURPOSE: Chemokines, including a chemoattractant for mononuclear cells CCL3 (MIP 1alpha), are responsible for attracting leukocytes into central nervous system (CNS) and cerebrospinal fluid (CSF) in meningitis and encephalomeningitis. We investigated the possibility of the involvement of CCL3 in tickborne encephalitis (TBE) pathogenesis. MATERIAL AND METHODS: We studied 26 patients with TBE; 13 with meningitis (group I) and 13 with encephalomeningits (group II). Control group included 11 patients without infectious disease of the CNS. CCL3 concentration was measured by ELISA in serum and CSF on admission (examination 1) and after 2 weeks (examination 2) in TBE patients and once in controls. RESULTS: In all control samples CCL3 concentration was below detection limit. In TBE, CCL3 serum concentration was: in group I--10.1 +/- 4.1 (mean +/- SD, ng/ml) in examination 1 and 12.4 +/- 4.8 in examination 2, and in group II--12.5 +/- 3.9 and 13.5 +/- 4.8, respectively. In CSF, CCL3 was detected: in group I in 5 patients in examination 1 (178 +/- 236 pg/ml) and 11 in examination 2 (457 +/- 215), in group II--in 8 (357 +/- 311) and 7 patients (326 +/- 330), respectively. There were no differences between group I and II. The comparison of CCL3 concentration gradient with albumin gradient between serum and CSF supported the possibility of intrathecal synthesis of CCL3. CONCLUSIONS: 1) Synthesis of CCL3, perhaps including intrathecal synthesis, is increased in TBE. 2) CCL3 concentration was much lower in CSF than in serum of the TBE patients, which argues against its significant role as chemoattractant in this condition. PMID- 17357338 TI - The emotional component of the attitude of the physician in situations of obstetric failure. AB - PURPOSE: The research aim is to study the working attitude of a physician towards his patient with obstetric failures in the emotional component aspect. MATERIAL AND METHODS: A sample of 164 gynecological doctors was encompassed by the study. The physicians were mainly interviewed during various types of training courses, specialist conventions and during personal meetings. A 44-question anonymous questionnaire was directed at gynecologists. The question was closed. The survey used for the research (in "ex post facto" procedure) matches quantity and quality elements. RESULTS: Concerning the emotional aspect referred to the most difficult in the physician-- patient relation: 18% of the respondents stated they had positive feelings towards the patient, 16% had self-centred feelings and 1% had negative feelings towards the patient. Concerned the feelings of the doctor when the patient and her husband are in a situation of obstetric failure: 49% shared positive feelings in experiencing obstetric failure in patients, 38% concentrated on themselves and their own feelings and 4% gave a decided negative reply. Physicians' attitudes were measured in relation to the death of a patient: 52% related that experience very personally to themselves, 4% of the physicians referred to the death of their patient with a sense of great sorrow and 1% were negatively trying to put the blame on the deceased patient. CONCLUSIONS: The most emotionally difficult obstetric failure in the doctor--patient relation was the death of a prenatal child; the most effective reaction to the sorrow of a mother after the loss of her child was support and bringing relief to the patient; 38% of gynecologists have not answered the question because of luck of such experience and because of the too difficult trauma experience. PMID- 17357339 TI - Influence of a physical exertion on the workers' health state. AB - PURPOSE: The health state of the workers employed at hard and very hard workplaces (on the ground of an energy expenditure measurement) has been presented in this report. MATERIAL AND METHODS: The morbidity of these workers was compared with the morbidity rates of two groups: the persons employed at a factory management and the workers performing light and moderate physical work. The number data has been standardized in order to eliminate the influence of an age over the morbidity rate values. RESULTS: A number of the considerably differences in frequency of the occurrence of each disease among the examined employees groups has been found. CONCLUSION: The diseases of the peripheral nervous system and locomotive organs as well as the disturbances of the cerebral circulatory were of more frequent occurrence among the persons performing hard and very hard work. PMID- 17357340 TI - [Robot-assisted laparoscopic surgery in gynecology: scientific dream or reality?]. PMID- 17357341 TI - [International comparison of perinatal care in the Czech Republic from the WHO viewpoint]. AB - OBJECTIVE: To verify the excellent level of perinatal care in the Czech Republic in the world-wide context. DESIGN: International comparative perinatal epidemiologic study. SETTING: Institute for the Care of Mother and Child, Prague. METHODS: Analysis of the relationship of perinatal mortality and 8 other selected indicators of perinatal care in 40 countries with perinatal mortality lower than 10 per thousand out of 192 WHO members states. RESULTS: The analysis pointed out than only 6-8 countries achieved the currently lowest perinatal mortality of 4-6 per thousand (out of which less than 2 per thousand are due to the ENM and 2-3 fold more due to the stillbirts, as well the lowest infant mortality (3-5 per thousand) and maternal mortality ratio (less than 15/100 live-born babies). The frequency od CS which was not above 20% in these countries was not interrelated with either perinatal or maternal mortality. In the Czech Republic, all the indicators were closer to lower levels what indicates that the Czech Republic belongs to the countries with the best results. The decreasing perinatal and maternal mortality led to the increasing expenses for the care and these were in negative correlation with the population density. The population density has an impact on the network of health care facilities and on the transport system of pregnant women, pathological newborns and newborn of very low birthweight to perinatal centers. CONCLUSION: Based on the results of the comparative analysis of perinatal mortality and 8 other selected indicators we can evaluate their reliability and also the level of perinatal care. The Czech Republic belongs among countries with the lowest perinatal mortality in the world. PMID- 17357342 TI - [Transvaginal hydrolaparoscopy and ultrasonographically guided transvaginal hydrolaparoscopy--two outpatient methods of pelvis examination]. AB - OBJECTIVE: The aim of this study is to describe transvaginal hydrolaparoscopy (THL) and ultrasonographically guided transvaginal hydrolaparoscopy (UTHL) used in the examination of the female pelvis in patients treated for infertility. Emphasis was placed on the safety of both procedures. SETTING: Fertimed, Infertility centre, Olomouc. METHODS: Transvaginal hydrolaparoscopy is an outpatient method for the examination of the female pelvis. Optics are inserted via the posterior vaginal wall and the tuboovarian complex is examined in saline solution. In ultrasonographically guided transvaginal hydrolaparoscopy, ultrasound is used during whole examination. The control of position of ultrasound instruments during the whole procedure increases the safety of the procedure and decreases difficulty of the method. RESULTS: 9 patients were examined with transvaginal hydrolaparoscopy. In 2 patients, (22%), insertion of the needle was complicated by bowel injury. Based on the experience with transvaginal hydrolaparoscopy we developed a modified version: Ultrasonographically guided transavaginal hydrolaparoscopy. With this method we examined 460 patients. Access to the abdominal cavity was successful in 100%. In 1.7%, the examination was not done due to a lack of fluid in Douglas space. Bowel injury was not detected. Visualisation of both adnexa was similar in both methods (94.5%). Small asymptomatic periovarial adhesions were found in 16%. In 5.2%, we found grade I endometriosis. Laparoscopy was recommended in 15.7% due to tubarian obstruction, severe adhesions, or poor adnexal visibility. Surgical intervention was necessary in 86.2% of those patients. CONCLUSIONS: Transvaginal hydrolaparoscopy and ultrasonographically guided transvaginal hydrolaparoscopy are new methods for examination of tuboovarian complex. Ultrasonographically guided transvaginal hydrolaparoscopy ensures safer and easier access to the abdominal cavity with low complication rate. PMID- 17357343 TI - [EmbryoGlue the transfer medium with hyaluronan in the IVF+ET program]. AB - OBJECTIVE: To assess, if the replacement of serum albumin by recombinant human albumin and hyaluronan in EmbryoGlue transfer medium effects embryo implantation within IVF+ET programme. DESIGN: A prospective study. SETTING: Department of Obstetric and Gynecology, University Hospital, Olomouc. METHODS: 297 IVF cycles with the embryotransfer (ET) were evaluated. The patients were divided into 2 groups according to the type of transfer medium (culture medium; G2.2, n = 112 and the transfer medium EmbyoGlue (EG) n = 185) and to three subgroups according to the age of the patients (< 30, 30-38, > 38). In both groups the following entry parameters were compared: average age, number of oocytes obtained, fertilization rate (FR), number of frozen embryos, number of transferred embryos. The outcome parameters compared were: pregnancy rate (PR), implantation rate (IR), abortions (AB) and the number of multiple pregnancies. RESULTS: In the group of patients up to 30 (EG = 72 vs. G2.2 = 51) and over 38 years of age EG = 18 vs. G2.2 = 18) no differences in input and output parameters have been discovered, while in the group of patients between 30 and 38 years of age (EG = 94 vs. G2.2 = 44) the results of EG group embryo implantation have been improved significantly (IR 27.7% vs. 153%, p < 0.01). No differences in any other output parameters have been encountered (PR 43.6% vs. 39.5%, AB 7.3% vs. 11.7%). CONCLUSION: Human serum albumin can be replaced by hyaluronan as a sole macromolecule in a human embryo transfer medium and by recombinant human albumin, without reduction of pregnancy rate (PR) and implantation rate (IR). Not only similar results were achieved in EG medium compared to currently used G2.2 medium, but in the group of 30-38 year old patients a statistically significant positive influence of EG on the implantation of embryos has been observed. PMID- 17357344 TI - [Efficiency of measuring nasal bone as an ultrasound marker of Down syndrome in 11th to 13th+6 week of pregnancy]. AB - OBJECTIVES: The aim of this study is to evaluate the significance of nasal bone as a marker for trisomy 21 in the group of women that underwent invasive procedures in our center at 11 to 14 weeks' gestation. METHODS: The data of 181 women who had undergone the invasive procedures were evaluated for the presence or absence of nasal bone retrospectively and were correlated with fetal karyotype. RESULTS: A successful view of the fetal profile was obtained in 135 fetuses. The nasal bone was absent in 5 of 8 fetuses with trisomy 21 and in 3 of 4 fetuses with trisomy 18. In the group of chromosomally normal fetuses the nasal bone was absent in 4 of the 123 cases. The false positive rate of our screening program dropped from 4.5% to 2.5% after the introduction of the nasal bone evaluation into our risk calculation model for trisomy 21. CONCLUSION: Nasal bone evaluation improved the detection of trisomy 21 in the first trimester in our screening program and reduced the need for invasive procedures in our department. Absence of the nasal bone showed a sensitivity of 63% for a 5% false positive rate for trisomy 21 in our study. It is rarely observed in chromosomally normal fetuses (2.5%). An appropriate training is mandatory in order to achieve acceptable results. PMID- 17357345 TI - [Does the detection of disease in asymptomatic period improve the prognosis of patients with endometrial carcinoma?]. AB - OBJECTIVE: To analyse factors which led to the diagnosis of endometrial carcinoma in patients still in asymptomatic stage and to find out if such early diagnosis has an impact on further prognosis of this carcinoma. DESIGN: Retrospective study. SETTING: Department of Obstetrics and Gynecology, Medical Faculty of the Palacky University and University Hospital, Olomouc. METHODS: The analysis of reasons which made the patients with endometrial carcinoma to see a gynecologist and estimate the proportion of preventive measures in the diagnosis malignant diseases of uterine corpus. RESULTS: The study included 110 patients with diagnosis of endometrial carcinoma. The Common symptoms of endometrial carcinoma, e.g. most often irregular bleeding, brought 87 (79%) patients to gynecologists while in remaining 23 (21%) of patients the disease was found in asymptomatic stage at the preventive oncogynecologic examination or incidentally at the examination for other illnesses. Both groups differed in staging and grading. CONCLUSIONS: The asymptomatic patients where the disease was diagnosed incidentally or during preventive oncogynecologic examination had, in the beginning of treatment, markedly lower staging and more favorable grading than symptomatic patients, what generates preconditions for a better prognosis of these patients. PMID- 17357346 TI - [Prospective study the prevalence of different candida strains and their sensitivity to different antimycotic treatment in women with vulvovaginal candidiasis]. AB - OBJECTIVE: Aim of this study was to ascertain the prevalence of differrent candida strains and their sensitivity to different antimycotic treatment in women with vulvovaginal candidosis. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, 1st Faculty of Medicine and the General Faculty Hospital, Charles University, Prague. UKLB, Clinical microbiology and ATB center, 1st Faculty of Medicine and the General Faculty Hospital, Charles University, Prague. Department of Obstetrics and Gynecology, Hospital Milosrdnych bratri, Brno. PATIENTS: 124 women with symptomatic vulvovaginal candidosis were included in the study between January and October 2003. After complete clinical exam, vaginal pH, wet prep, the cultures were taken for special fungal examination. RESULTS: In 92% of patient was confirmed infection with C. albicans, from topical antifugal agents were most sensitive to nystatin and pimaricin (100% cases), from oral antifugal agents to fluconasol, itraconasol and ketokonasol in 97-98% cases. C. nonalbicans strains were confirmed in 8% cases of vaginitis and there were similiar sensitivity to topical antifugal agents as in C. albicans strains. To oral antifugal agents there were in 10% resistance to fluconasol and in 20% to itraconasol. CONCLUSION: In this study we did not confirmed the higher prevalence of C. nonalbicans strains in vulvovaginal candidiasis, in literature the prevalence is 10-15%. We did not confirmed the increasing resistance to antifugal agents. PMID- 17357347 TI - [Vulvovaginitis. Occurrence and importance of mixed and unclassifiable pictures]. AB - OBJECTIVE: To evaluate the occurrence of mixed and unclassifiable vulvovaginitis (i.e. those, which fulfill the diagnostic criteria of several diagnostic units or no diagnostic unit) in symptomatic and asymptomatic women. TYPE OF STUDY: Prospective study. METHODS: In 412 women (115 of them asymptomatic) the authors established the diagnosis of vulvovaginitis on the basis of gynecological examination, pH, the amine test and microscopic examination according to Giemsa and Gram. RESULTS: Mycosis was diagnosed in 15.5% women (in 9,6% of asymptomatic ones), lactobacillosis in u 5.6% (in 7.0% of asymptomatic), anaerobic vaginosis in 10.7% (8.7% of asymptomatic), aerobic vaginitis in 7.7% women (4.3% of asymptomatic). U 15.0% mixed infections were diagnosed (in 61% asymptomatic). U 29.4% symptomatic women the diagnostic criteria were not fulfilled for any nosological unit. CONCLUSION: Vulvovaginal mycosis, lactobacillosis, anaerobic vaginosis, aerobic vaginosis were considered as dysmicrobia conditions. The authors demonstrated a high occurrence of more units ("clear" diagnoses to "mixed" diagnoses being in the ratio of 1.62:1). The authors also demonstrated a high occurrence of mixed infections in asymptomatic women (36.0%). On the contrary, in 29.4% of symptomatic women the diagnosis could not be established, the findings being "normal" or "unclassifiable". PMID- 17357348 TI - [Prophylactic HPV vaccination]. AB - OBJECTIVE: To present a review on the contemporary degree of the development of prophylactic HPV vaccines. DESIGN: Review article. SETTING: Department of Obstetrics and Gynaecology, 1st Medical Faculty and General Faculty Hospital, Charles University, Prague, Czech Republic. METHODS: Literature review. CONCLUSION: The contemporary knowledge about relation of HPV infection and cervical cancer gives a theoretical presumption for the development of prophylactic HPV vaccines. Results of extended studies of quadrivalent and bivalent HPV vaccines justify to expect their soon introduction to clinical practice. PMID- 17357349 TI - [TVT SECUR System--tension-free support of the urethra in women suffering from stress urinary incontinence--technique and initial experience]. AB - OBJECTIVE: The aim of the article is to present a new, minimally invasive sling procedure for the treatment of the stress urinary incontinence in women--the TVT S System (tension-free vaginal tape secure system). DESIGN: Cross-sectional clinical study. SETTINGS: Gynecological and Obstetric Clinic, 1 LF UK and VFN, Prague. MATERIALS AND METHODS: We present the technique employed in the operation, the examination procedure including US examination before and after the operation, at rest and during Valsalva manoeuvre, and the subjective and objective outcome in our group. This study is intended to determine the curative effect and the complications associated with TVT S procedure. The clinical study included 15 women with previously untreated stress urinary incontinence. Their mean age was 53.1, mean body mass index (BMI) 27.73, and mean parity 1.86. The tape was placed ten times in a "Hammock" position and five times in a "U" position. RESULTS: All patients are between one and three months after the operation. The curative rate is 93%. The complications of the TVT S are as follows: when the tape was placed in the "Hammock" position, in one case slight SUI (stress urinary incontinence) persisted; the tape was folded in two cases; one patient suffered from pain in the vagina after this procedure. In one case we found vaginal erosion caused by the tape; the size of the erosion was about 3 mm. We did not find any complications after TVT S procedure when the tape was placed in the "U" position. CONCLUSIONS: Our experience with TVT S procedure including possible complications, postoperative care and curative rate is positive. TVT S with two approaches "U" and "Hammock" gives us one tool for both main groups of patients with SUI. In the group of patients with larger mobility of the urethra it might be better to place the tape in the "Hammock" position: this procedure is simpler and quicker. In the group of patients with less mobility of the urethra it seems that to use the tape in the "U" position is the better option, this procedure is longer and slightly more difficult. PMID- 17357351 TI - [Ovarian hypertimulation syndrome: a review]. AB - OBJECTIVE: Discuss prevalence, risk factors, pathophysiology, symptoms, complications and therapy of OHSS. DESIGN: A review article. SETTING: Department of Obstetrics and Gynaecology, 1st Faculty of Medicine and General faculty Hospital, Charles University, Prague. SUBJECT AND METHODS: A review from literature and bibliographic databases. RESULTS: OHSS is an iatrogenic complication of ovarian stimulation. We still can not completely explain the pathophysiology of OHSS. The therapy is based on symptomatic approach. To prevent OHSS, the hCG should not be given to induct the ovulation, or we should not transfer embryos during the IVF-stimulated cycle. PMID- 17357350 TI - [Choroid plexus cysts and risk of trisomy 18. Modifications regarding maternal age and markers]. AB - OBJECTIVE: Our aim was to evaluate the risk of chromosomal abnormalities esp. trisomy 18, associated with isolated choroid plexus cyst(s) in pregnant women undergoing second-trimester ultrasonographic examination. DESIGN: A review article. SETTING: OBGYN clinic of the 1st faculty of medicine, Prague, Teaching hospital Bulovka. SUBJECT: Choroid plexus cyst(s) (CPC) are more common in fetuses with chromosomal aneuploidies, particularly trisomy 18. Although it is accepted that the risk of karyotypic abnormality justifies amniocentesis in the case of other associated abnormalities are present, disagreement continues as to the risk of trisomy 18 in a fetus with an isolated choroid plexus cyst. We evaluated additional consideration of maternal age and multiple-marker screening for chromosomal aneuploidy in the assessment of risk. CASE REPORT: We report a trisomy 18 case that was diagnosed on the basis of CPC detection by ultrasound, NMR, and further amniocentesis. CONCLUSION: It is well accepted that choroid plexus cyst(s) in association with other congenital anomalies warrant amniocentesis to determine fetal karyotype. The presence of isolated CPC varies around 1% in general population, but around 30% in fetuses with trisomy 18 where the prevalence is 3 per 10,000 pregnancies. Metaanalyses reported incidence of trisomy 18 of 1 in 374 in fetuses with isolated CPC. These risks do not exceed the 1:200 risk of pregnancy loss after amniocentesis and also the 1:270 risk of Down syndrome (DS) in a 35-year-old woman, but exceeds the risk for DS of a 37 year-old woman. Thus these findings suggest that amniocentesis should not be offered to pregnant women in the presence of isolated fetal choroid plexus cyst(s), but in the absence of other pathologies. Amniocentesis is then justified only in the patient with advanced maternal age. PMID- 17357352 TI - [Remarks on embolization of uterine fibroids]. AB - OBJECTIVE: To give a systematic comment on uterine artery embolization for the treatment of uterine fibroids. DESIGN: Expert comment. SETTING: Department of Obstetrics and Gynecology, 1st Faculty of Medicine and General Faculty Hospital, Charles University, Prague. METHODS: The analysis of results of the group of patients treated with uterine fibroid embolization in our facility in the years 2001-2005. RESULTS: Opinions of the multidisciplinary team, specialized in complex therapy of uterine fibroids were summarized. On the base of experience with more than 110 patients treated with uterine fibroid embolization we worked up practical comments on indications, cover and implementation of the procedure, and on suggested studies pre and post-procedurally with regard to expected effect and possible complications. CONCLUSION: Uterine artery embolization is a minimally invasive procedure with large symptomatic potential in therapy of post fertile females with leiomyomas. The indication of such therapy for pregnancy planning women is controversial and needs thorough individual consideration about benefits and risks of embolization and its comparison with standard therapy (myomectomy). Organizing of the whole procedure (preoperative studies, equipment and experience of interventional radiologist, pain management, handling with complications) is challenging and should be performed by specialized teams and centers. PMID- 17357353 TI - [Laparoscopic myomectomy: indications and limits]. AB - OBJECTIVE: An analysis of indication and limits of laparoroscopic myomectomy with regard to clinical usefulness. DESIGN: A short review article. SETTING: Department of Obstetrics and Gynecology, Endoscopic Training Centre, Hospital, Kladno, Czech Republic. SUBJECT AND METHOD: One of the primary goals of laparoscopic myomectomy is preservation of the uterus for the future fertility and psychosomatic integrity of women through minimally invasive way. A comparison is made of advantage and disadvantage of different types of myomectomy. CONCLUSION: Laparoscopic myomectomy is surgical alternative for women with symptomatic subserosal and intramural fibroids. The indication for this technique is limited. Removal of large fibroids and repair of myometrial defect are challenges to gynecologic laparoscopists, and also the main limitations. A well trained laparoscopic surgical team can operate any fibroid. In our experience, as well as reflected by the literature, a consensus gradually emerges that a maximal size of 8-10 cm and a total number of fibroids should not exceed four. PMID- 17357354 TI - [Ovarian tissue cryopreservation--an opportunity to preserve fertility in women with cancer]. AB - Chemoterapy is one of the basic modalities of oncological therapy and usually leads to permanent consequences. Infertility is one of the most common consequences resulting from irreversible gonadal damage. The potentially effective method of reproductive function protection in women undergoing chemotherapy is ovarian tissue cryopreservation. This paper summarizes the medical and scientific knowledge in this interesting multidisciplinary medical field an also presents authors own experience with this novel and interesting method of ovarian tissue protection. PMID- 17357355 TI - Carbon monoxide: the case for environmental public health surveillance. PMID- 17357356 TI - Results from a state-based surveillance system for carbon monoxide poisoning. AB - OBJECTIVES: The purpose of this study was to describe results from a pilot surveillance system for carbon monoxide poisoning--a significant yet preventable public health issue for which most public health agencies do not conduct routine public health surveillance. METHODS: The authors developed a rate-based statewide surveillance system. Cases were identified using the 1998 Council of State and Territorial Epidemiologists' case definition in hospital discharges, emergency department and hospital outpatient visits, and mortality data. Intentional and fire-related injuries were excluded. The system was supplemented with qualitative information from newspaper articles. Annual, age, and sex-specific incidence rates were estimated. Exposure source/setting was described using E-codes; occupational setting was assessed by combining E-codes and payer code. Cases occurring during a disaster-related power outage in January 1998 were compared with cases identified during routine surveillance from 1999 through 2003. RESULTS: During the five years of routine surveillance, 740 cases were identified; 47 (6.4%) were hospitalized, 442 (59.7%) were seen in an emergency department, and 251 (34.3%) were seen in another outpatient setting. More cases were observed in fall/winter; 23.1% of patients aged 16 or older were classified as exposed in an occupational setting. Among disaster-related cases, more were older (> or =65 years of age; 11.9% vs. 4.2%) and female (61.6% vs. 45.3%); and fewer were in occupational settings (1.8% vs. 23.1%). CONCLUSIONS: Establishing state-based public health surveillance for CO poisoning is feasible and essential for guiding prevention and control efforts. The finding that more than 20% of cases were classified as occupational should be investigated further. PMID- 17357357 TI - Chickenpox exposure and herpes zoster disease incidence in older adults in the U.S. AB - OBJECTIVES: Exposure to varicella zoster virus through close contact with people with chickenpox was suggested to boost specific immunity, reducing the risk of herpes zoster (HZ). Since the introduction of the varicella immunization program in the US in 1995, varicella morbidity has decreased substantially. This article examines incidence and risk factors associated with self-reported HZ disease and whether exposure to chickenpox within the previous decade reduces the risk of shingles in this age group. METHODS: In 2004, a national random-digit dial telephone survey was used to obtain information on self-reported HZ disease, demographic characteristics, and exposure to children with chickenpox in the past decade. National estimates of the incidence of shingles disease were calculated. RESULTS: Incidence rate of self-reported HZ was 19 per 1,000 population per year. White individuals were 3.5 times more likely to report shingles than Hispanic individuals (p<0.01). Previous exposure to chickenpox did not protect against HZ disease in this population. Seven percent of adults > or =65 years of age reported exposure to children with chickenpox in the past decade. CONCLUSIONS: Incidence of HZ among individuals > or =65 years of age in the U.S. may be higher than previously described in the literature, with whites being at higher risk for the disease. Currently, the potential contribution of exposure to chickenpox as a mechanism for maintaining cell-mediated immunity against HZ may be limited to a small percentage of the population. Vaccination against HZ may represent the best means of decreasing this disease burden. PMID- 17357358 TI - Estimating health care-associated infections and deaths in U.S. hospitals, 2002. AB - OBJECTIVE: The purpose of this study was to provide a national estimate of the number of healthcare-associated infections (HAI) and deaths in United States hospitals. METHODS: No single source of nationally representative data on HAIs is currently available. The authors used a multi-step approach and three data sources. The main source of data was the National Nosocomial Infections Surveillance (NNIS) system, data from 1990-2002, conducted by the Centers for Disease Control and Prevention. Data from the National Hospital Discharge Survey (for 2002) and the American Hospital Association Survey (for 2000) were used to supplement NNIS data. The percentage of patients with an HAI whose death was determined to be caused or associated with the HAI from NNIS data was used to estimate the number of deaths. RESULTS: In 2002, the estimated number of HAIs in U.S. hospitals, adjusted to include federal facilities, was approximately 1.7 million: 33,269 HAIs among newborns in high-risk nurseries, 19,059 among newborns in well-baby nurseries, 417,946 among adults and children in ICUs, and 1,266,851 among adults and children outside of ICUs. The estimated deaths associated with HAIs in U.S. hospitals were 98,987: of these, 35,967 were for pneumonia, 30,665 for bloodstream infections, 13,088 for urinary tract infections, 8,205 for surgical site infections, and 11,062 for infections of other sites. CONCLUSION: HAIs in hospitals are a significant cause of morbidity and mortality in the United States. The method described for estimating the number of HAIs makes the best use of existing data at the national level. PMID- 17357359 TI - The public's preparedness for hurricanes in four affected regions. AB - OBJECTIVES: The purpose of this article is to look at how prepared people in communities outside the main areas devastated by Hurricanes Katrina and Rita thought they were for those storms and for major hurricanes in the near future, what factors were related to why people did not evacuate, and what concerns people had in communities that took in evacuees from the hurricanes. METHODS: Telephone interviews were conducted with randomly selected adults in Baton Rouge, Houston, Dallas, and Mississippi/Alabama (excluding the immediate Gulf Coast) to assess respondents' knowledge, attitudes, and behaviors about hurricane preparedness and response to Hurricanes Katrina and Rita. RESULTS: The surveys found a sizeable proportion of respondents who might not, for a number of reasons, comply with future orders to evacuate. A substantial proportion reported that they were not prepared for another major hurricane and indicated a desire for more information about how to prepare for future hurricanes. In communities that reported taking in large numbers of evacuees, residents expressed concern about the impact of the evacuees on their community. CONCLUSION: Evacuating communities involves a number of concrete problems that were not adequately addressed in the cases of Hurricanes Katrina and Rita. Responses to these surveys indicate a need for more comprehensive hurricane disaster planning. PMID- 17357361 TI - Extending Medicaid coverage for family planning services: Alabama's first four years. AB - OBJECTIVES: This study examines whether Alabama's Medicaid family planning demonstration program reaches a different segment of the population than the health department-based Title X family planning program, whether service use rates differ across clients using care within and outside of the Title X provider system, and whether additional risk assessment and care coordination services provided by health department personnel increase the likelihood that family planning clients return for follow-up visits over time. METHODS: Administrative data from four years of operation of the program were used to examine characteristics of the clientele, differences in services used across provider types included in the program, and the impact of risk assessments and care coordination on return visit rates. RESULTS: The number of family planning service users increased dramatically over the four-year period, but were more similar demographically to Title X clients than to Medicaid maternity clients. Growth was greatest among clients of non-Title X providers. Newly covered services, including risk assessments and care coordination, were available mostly to Title X clients, and these services were associated with a greater likelihood that clients returned for care in subsequent years. CONCLUSION: Expanded provider networks can increase the number of low income women using family planning services while risk assessment and care coordination can improve the effectiveness of these services. However, enhanced services may not be equally available across provider systems. Additional outreach efforts are needed to reach women eligible for publicly supported family planning services who are not currently using these services. PMID- 17357360 TI - Trends in socioeconomic inequalities in adult health behaviors among U.S. states, 1990-2004. AB - OBJECTIVE: The purpose of this study was to measure state trends in educational inequalities in smoking, binge alcohol use, physical inactivity, obesity, and seatbelt use. METHODS: The authors calculated the Relative Concentration Index of educational inequality for five health behaviors on adults from all 50 states and the District of Columbia using data from 1990 to 2004 in the Behavioral Risk Factor Surveillance System (n=2,118,562). Linear regression was used to measure changes and trends in the Relative Concentration Index of health inequality across education groups in each state. RESULTS: Except for binge alcohol use, poorer health behaviors were concentrated among the less educated. The largest educational inequalities were for physical inactivity. From 1990 to 2004, significant increases in relative educational inequalities occurred in 40 states for smoking and 31 states for physical inactivity. For binge alcohol use, 27 states showed significant declining inequality trends, but educational inequalities reversed direction and binge alcohol use is now more prevalent among the less educated in 19 states. Significant decreases in educational inequalities occurred in 36 states for obesity and 24 states for seat belt use. Changes in educational inequalities across the different health behaviors were not associated, except for a modest correlation between changes in inequality in smoking and binge alcohol use (r=0.40; p=0.004). Similarly, there was little association between changes in the population prevalence of health behaviors and changes in educational inequality in health behaviors, with substantial heterogeneity among states. CONCLUSIONS: State trends in relative educational inequality among health behaviors were mixed, increasing for smoking and physical inactivity and decreasing for obesity and seat belt use. The factors influencing relative inequality trends may differ from those affecting overall prevalence trends. PMID- 17357362 TI - Determining the effect of newborn hearing screening legislation: an analysis of state hearing screening rates. AB - OBJECTIVE: This study was conducted to determine the effect of state Universal Newborn Hearing Screening legislation on the percentage of infants having their hearing screened within one month of birth. METHODS: Hearing screening data for 2000-2003 were obtained from state hearing screening programs. States with Universal Newborn Hearing Screening legislation were categorized according to legislation type and implementation status, and hearing screening rates were compared between states with implemented legislation and states with no legislation. RESULTS: Hearing screening rates among states that implemented Universal Newborn Hearing Screening legislation were significantly higher than rates in no-legislation states throughout the study period, although the mean screening rate among no-legislation states increased substantially from 2000 through 2003. The percentage of states attaining a 95% national screening quality indicator in each year was substantially greater among states with implemented legislation. In 2003, 76% of states with implemented Universal Newborn Hearing Screening legislation reported screening at least 95% of infants, compared with 26% of states without legislation. Although there is a greater likelihood of meeting the national screening target with Universal Newborn Hearing Screening legislation than without, other factors such as collaborative relationships and federal funding can also influence this outcome. CONCLUSION: State legislation has had a positive effect on hearing screening rates and is one tool states can use to help ensure that infants are screened for hearing loss. PMID- 17357363 TI - Low income parents' reports of communication problems with health care providers: effects of language and insurance. AB - OBJECTIVES: This study examines how parental reports of communication problems with health providers vary over a wider range of characteristics of low income children than considered in previous studies. METHODS: Data were drawn from the 1999 and 2002 National Survey of America's Families. Communication problems, insurance type, socioeconomic characteristics, health factors, and provider type were examined. Data were analyzed using bivariate and multivariate techniques. RESULTS: Bivariate analysis identified that the parents of 24.4% of low income children and 36.4% of publicly covered low income children with a Spanish interview reported poor communication with health providers. Coefficients from regression analysis suggest that, controlling for covariates, foreign-born parents with a Spanish interview were 11.8 percentage points (p<0.01) more likely to report communication problems than U.S.-born parents with an English interview. Among low income publicly covered children with a Spanish interview, regression analysis suggests that parents of children who used clinics or hospital outpatient departments as their usual source of care were 9.5 percentage points (p<0.05) more likely to report communication problems compared with those whose usual source of care was a doctor's or HMO office. CONCLUSIONS: Implementing policies to improve communication barriers for low income children, particularly those with foreign-born parents whose native language is not English, may be necessary to reduce health disparities relative to higher income children across a variety of health domains including utilization, satisfaction, and outcomes. Focusing attention on the availability of professional translation services in clinics or hospital outpatient departments may be a cost-effective strategy for reducing communication problems for publicly insured children. PMID- 17357364 TI - Outcomes in men denied access to a California public assistance program for prostate cancer. AB - OBJECTIVES: To improve access to prostate cancer treatment for low income uninsured men, California initiated a program called IMPACT: Improving Access, Counseling and Treatment for Californians with Prostate Cancer. The program administered free treatment, case management, counseling, and educational materials to all eligible men until budget cuts led to a state-mandated suspension of enrollment and the establishment of a temporary waitlist in February 2005. To assess the effect of suspension of enrollment on patient outcomes, the authors compared health-related quality of life (HRQOL) in waitlisted and enrolled men. METHODS: Eighty-three men in each group were matched on disease stage, age, and race. HRQOL was captured with the UCLA Prostate Cancer Index short form (PCI-SF), the Medical Outcomes Study Short Form-12 (SF-12), and McCorkle and Young's Symptoms and Degrees of Distress in Patients with Cancer Scale (SDS). Self-efficacy was measured with the Perceived Efficacy in Patient Physician Interactions (PEPPI) Questionnaire. RESULTS: At intake, waitlisted men demonstrated significantly more symptom-related distress (2.9; p=0.04) and less perceived self-efficacy (2.5; p=0.005) compared to enrollees. Waitlisted men were significantly less likely to have access to a doctor or nurse case manager, treatment medications, nutrition information, or counseling services (p<0.0001). CONCLUSIONS: Men denied enrollment into the IMPACT program exhibited significantly worse symptom distress and self-efficacy compared to enrolled men at initial assessment. The multivariate model suggests that HRQOL in the waitlisted men may be related to their lack of access to medical services. This data illustrates the importance of ongoing public assistance for low income men with prostate cancer. PMID- 17357365 TI - Prevalence of residential smoke alarms and fire escape plans in the U.S.: results from the Second Injury Control and Risk Survey (ICARIS-2). AB - OBJECTIVES: This study was conducted to estimate (1) the proportion of U.S. homes with installed smoke alarms and fire escape plans, and (2) the frequency of testing home smoke alarms and of practicing the fire escape plans. METHODS: The authors analyzed data on smoke alarms and fire escape plans from a national cross sectional random-digit dialed telephone survey of 9,684 households. RESULTS: Ninety-five percent of surveyed households reported at least one installed smoke alarm and 52% had a fire escape plan. The prevalence of alarms varied by educational level, income, and the presence of a child in the home. Only 15% tested their alarms once a month and only 16% of homes with an escape plan reported practicing it every six months. CONCLUSION: While smoke alarm prevalence in U.S. homes is high, only half of homes have a fire escape plan. Additional emphasis is needed on testing of installed smoke alarms and on preparedness for fire escape plans. PMID- 17357366 TI - Acute pesticide poisoning in the U.S. retail industry, 1998-2004. AB - OBJECTIVE: This study was conducted to describe the national magnitude and characteristics of acute pesticide poisoning among workers and customers in retail establishments. METHODS: Analyses included retail employees 15-64 years of age and customers with acute pesticide poisoning identified from the Sentinel Event Notification System for Occupational Risks-Pesticides (SENSOR-Pesticides) and California Department of Pesticide Regulation from 1998 to 2004. Pesticide poisoning incidence rates and incidence rate ratios (IRR) were calculated. RESULTS: A total of 325 cases of acute pesticide poisoning were identified. Of these cases, 287 (88%) were retail employees and 38 (12%) were customers. Overall, retail employees had a significantly lower acute pesticide poisoning incidence rate compared with non-agricultural, non-retail employees (IRR=0.53; 95% confidence interval 0.47, 0.59). However, significantly elevated pesticide poisoning incidence rates were observed for four retail occupations (janitors, stock handlers/baggers, bakery/deli clerks, and shipping/receiving handlers). In addition, workers employed in two retail industry sectors (farm supply stores and hardware stores) had significantly elevated acute pesticide poisoning incidence rates. Incidence rates among the retail employees demonstrated a quadratic trend, monotonically decreasing from 1998 to 2000 and monotonically increasing from 2000 to 2003. The rates appear to have leveled off in 2003 and 2004. CONCLUSIONS: Preventive measures to decrease acute pesticide poisoning incidence in the retail sector include adoption of unbreakable and tear-resistant container requirements, increased utilization of integrated pest management strategies, and advisement to store managers, employees, and customers about poisoning prevention. PMID- 17357367 TI - Prescribing prevention to treat urban violence. PMID- 17357368 TI - Immunity for the people: the challenge of achieving high vaccine coverage in American history. PMID- 17357369 TI - Development of a diabetes prevention management program for clinical practice. PMID- 17357370 TI - Medicaid and documentation of legal status: implications for public health practice and policy. PMID- 17357371 TI - Academic public health community responds to hurricanes: a history of the University of North Carolina School of Public Health response and new infrastructure, 1999-2006. PMID- 17357372 TI - Comparative pharmacology of the H1 antihistamines. PMID- 17357373 TI - Effect of H1 antihistamines upon the cardiovascular system. PMID- 17357374 TI - Effect of H1 antihistamines upon the central nervous system. PMID- 17357375 TI - Interactions of the H1 antihistamines. PMID- 17357376 TI - H1 antihistamines: psychomotor performance and driving. PMID- 17357377 TI - Long-acting anticoagulant rodenticide poisoning: an evidence-based consensus guideline for out-of-hospital management. AB - The objective of this guideline is to assist poison center personnel in the out of-hospital triage and initial management of patients with suspected exposure to long-acting anticoagulant rodenticides (LAAR). An evidence-based expert consensus process was used to create this guideline. It is based on an assessment of current scientific and clinical information. The panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and health professionals providing care. The grade of recommendation is in parentheses. 1) Patients with exposure due to suspected self harm, abuse, misuse, or potentially malicious administration should be referred to an emergency department immediately regardless of the doses reported (Grade D). 2) Patients with symptoms of LAAR poisoning (e.g., bleeding, bruising) should be referred immediately to an emergency department for evaluation regardless of the doses reported (Grade C). 3) Patients with chronic ingestion of LAAR should be referred immediately to an emergency department for evaluation of intent and potential coagulopathy (Grade B). 4) Patients taking anticoagulants therapeutically and who ingest any dose of a LAAR should have a baseline prothrombin time measured and then again at 48-72 hours after ingestion (Grade D). 5) Patients with unintentional ingestion of less than 1 mg of LAAR active ingredient can be safely observed at home without laboratory monitoring. This includes practically all unintentional ingestions in children less than 6 years of age (Grade C). 6) Pregnant patients with unintentional exposure to less than 1 mg of LAAR active ingredient should be evaluated by their obstetrician or primary care provider as an outpatient. Immediate referral to an ED or clinic is not required (Grade D). 7) Patients with unintentional ingestion of 1 mg or more of active ingredient and are asymptomatic should be evaluated for coagulopathy at 48 72 hours after exposure (Grade B). 8) Physicians' offices or outpatient clinics must be able to obtain coagulation study results in a timely manner, preferably in less than 24 hours, for patients who require outpatient monitoring (Grade D). 9) Gastrointestinal decontamination with ipecac syrup or gastric lavage is not recommended (Grade D). 10) Transportation to an emergency department should not be delayed for administration of activated charcoal (Grade D). 11) Patients with dermal exposures should be decontaminated by washing the skin with mild soap and water (Grade D). 12) The administration of vitamin K is not recommended prior to evaluation for coagulopathy (Grade D). PMID- 17357378 TI - Quantifying morbidity associated with the abuse and misuse of opioid analgesics: a comparison of two approaches. AB - BACKGROUND: Due to the rising nonmedical use of opioid analgesics, methods are needed to quantify the associated health-related consequences. METHODS: Using opioid analgesic intentional exposure reports from poison control centers from January 2003-June 2004, we calculated quarterly rates for 7 opioids at the 3 digit ZIP code level using population- and patient-based denominators. RESULTS: Hydrocodone was the most widely prescribed opioid (maximum: 5,321,390 patients per quarter), with the largest intentional exposure caseload (range: 498-1,290), and the highest aggregate population-based rate (maximum of 13.61 cases per 1,000,000 individuals). Methadone had the highest aggregate patient-based rate (maximum 2.03 cases per 1,000 patients). CONCLUSION: Population- and patient based rates are complementary tools that address different public health questions. Population-based rates describe the health-related burden of nonmedical opioid analgesic use on the community as a whole, while patient-based rates show this burden ("risk") in relation to the level of corresponding medicinal use ("benefit") within a given area. PMID- 17357379 TI - Renal and liver transplantation for toxin-induced organ failure. AB - OBJECTIVE: Determine the number and outcome of renal (January 1987-June 2001, inclusive) and liver transplants (January 1993-June 2001) performed in Ireland for drug or toxin-induced organ failure and identify the toxins involved. METHODS: Retrospective review of national transplant coordinators' records and patient charts. RESULTS: Fourteen patients received renal transplants for nephropathy secondary to drugs or toxins. In 12 of these cases, renal failure was attributed to chronic toxicity, principally cyclosporin A therapy (seven cases). One-year patient and graft survival were 100%. Twenty-nine liver transplants were for toxin-induced organ failure, and 20 of these were for chronic ethanol induced liver disease. One-year patient and graft survival rates were 77% and 73%, respectively. CONCLUSIONS: Kidney and liver transplants were needed more often because of chronic toxicity than acute poisoning. Both groups had good outcomes at one year post-transplantation. PMID- 17357380 TI - Aminotransferase activities in healthy subjects receiving three-day dosing of 4, 6, or 8 grams per day of acetaminophen. AB - INTRODUCTION: This multiple-dose pharmacokinetic study has a randomized, double blind, placebo-controlled, parallel-group design with three dosing regimens. Healthy subjects received repeated doses of acetaminophen (4 then 6 g/d or 4 then 8 g/d) or placebo. METHODS: The disposition of acetaminophen and its metabolites and the tolerability of increased acetaminophen doses over 3 days of continuous consumption were characterized. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities measured throughout the study were consistent across the acetaminophen 4, 6, and 8 g/d dose levels and with placebo. RESULTS: Serum aminotransferase activities did not exceed the upper limit of the reference range (ULRR), except for one subject with an AST of 43 U/L (ULRR, 42 U/L), which was not considered clinically significant. All doses were generally well tolerated. CONCLUSIONS: In a multiple-dose pharmacokinetics study of 4, 6, and 8 g/d of acetaminophen for 3 days, multiple aminotransferase determinations demonstrated no clinically important elevations at 1, 1.5, or 2 times the maximum recommended acetaminophen dose. PMID- 17357381 TI - Lack of significant toxicity after mirtazapine overdose: a five-year review of cases admitted to a regional toxicology unit. AB - INTRODUCTION: Mirtazapine is a comparatively new antidepressant that selectively blocks central alpha2-adrenergic autoreceptors and postsynaptic 5-HT2 and 5-HT3 receptors, causing reduced neuronal norepinephrine and serotonin reuptake. The prevalence of mirtazapine prescribing has steadily risen; however, comparatively little information is available regarding the clinical features associated with mirtazapine overdose. AIMS: To characterize the toxic features that result from mirtazapine overdose. METHODS: We performed a retrospective case analysis of patients admitted to the Toxicology Unit of the Royal Infirmary of Edinburgh between January 2000 and December 2004 after stated mirtazapine overdose. Casenotes were examined for clinical, laboratory, and electrocardiographic safety data. RESULTS: There were 117 mirtazapine cases where the median (interquartile range) stated dose ingested was 450 mg (240-785 mg). Conscious level was reduced in 27.2% of patients and there was a higher incidence of tachycardia (30.4%) than predicted from normal reference range values (p < 0.001). There was no evidence of any other significant clinical, laboratory, or electrocardiographic abnormality. CONCLUSIONS: Severe toxic features could be attributed to other co ingested drugs or alcohol. The adverse clinical effects attributable to mirtazapine overdose appeared mild and predictable. Mirtazapine overdose appears to be associated with fewer features of severe toxicity than previously reported for other antidepressants. PMID- 17357382 TI - Atomoxetine-induced hepatitis in a child. AB - OBJECTIVE: To report a case of hepatitis associated with atomoxetine hydrochloride use and to describe the previously-unpublished severe cases of this syndrome. CASE SUMMARY: An eight-year-old female with attention deficient hyperactive disorder (ADHD) was treated with atomoxetine hydrochloride. She complained of increased abdominal pain and occasional emesis; her transaminases and bilirubin were markedly elevated. She was admitted to a tertiary-care pediatric hospital and treated for drug-induced hepatitis. Atomoxetine was discontinued and supportive care was instituted. A liver biopsy showed hepatitis with moderate piecemeal necrosis. Clinical status and liver function tests improved over 13 days of hospitalization. DISCUSSION: To our knowledge this is the first published severe case of atomoxetine-induced hepatitis. The International Organization of Medical Science Diagnostic Scale and the Adverse Drug Reaction Probability Scale by Naranjo et al. were applied to assess causality. Both scales indicated the association of atomoxetine and hepatitis as "probable;" a positive rechallenge would have made this association "definitive." This potential serious adverse reaction should be considered in children receiving atomoxetine therapy. PMID- 17357383 TI - The use of vasopressin in the setting of recalcitrant hypotension due to calcium channel blocker overdose. AB - Treatment of hypotension caused by calcium channel blocker overdose (CCB) remains a challenge. We describe the successful use of vasopressin in two patients with massive CCB overdoses in whom hypotension was unresponsive to calcium, glucagon, insulin, and conventional vasopressor therapies. While various modes of treatments have been used to treat the hypotension of CCB overdose, this is the first report to our knowledge of the successful use of vasopressin in this clinical setting. PMID- 17357384 TI - Gaboon viper (Bitis gabonica) envenomation resulting from captive specimens--a review of five cases. AB - BACKGROUND: Five cases of illegitimate bite by captive specimens of the Gaboon viper (Bitis gabonica) snake have demonstrated the dangers of keeping exotic African snakes in captivity. CASE SERIES: Four cases necessitated hospitalization for the bite and were characterized by progressive swelling of the affected limb, local necrosis and hemorrhagic edema near the wound, chest tightness and prolonged coagulation times. However, platelet counts were not altered. All patients received antivenom and had uneventful recovery, except for one who underwent amputation of a distal phalanx and one who required debridement. In the fifth case, the patient died without being able to summon help. DISCUSSION: The results of this case series emphasize the need for extreme care to be exercised with the captivity of exotic snakes, such as the Gaboon viper. The increasing popularity of this snake as a captive pet predicates the need for private collectors to have a pre-existing treatment strategy with their local emergency centers. Such arrangements may facilitate the treatment of envenomation by this snake. PMID- 17357385 TI - Cocaine-related peripheral vascular occlusive disease treated with iloprost in addition to anticoagulants and antibiotics. AB - We describe a case of acute ischemia of the 2nd, 3rd and 4th fingers of the right hand secondary to peripheral vascular occlusive disease induced by repeated intra arterial cocaine injections. The complete occlusion of the distal arteries resolved following treatment with iloprost, a synthetic stable analogue of prostacyclin PGI2, in addition to anticoagulants and antibiotics. PMID- 17357386 TI - Neurotoxicity of nitrous oxide: multimodal evoked potentials in an abuser. AB - INTRODUCTION: Nitrous oxide (N2O) damages the nervous system of chronic abusers. Multimodal evoked potentials (EPs) can help document the electrophysiological abnormalities of N2O abusers and its distribution in the nervous system. CASE REPORT: A 41-year-old male N2O abuser had used N2O (4-5 cans/per day, about 2000 ml/can) for more than 10 years. He complained of progressive motor clumsiness and distal paresthesia in the four limbs. Abnormal laboratory tests were megaloblastic red blood cells (102.3 fL, normal 80-94 fL) and serum vitamin B12 concentration of 143 pg/nL (normal 160-970 pg/nL). An MR image did not show significant findings in the brain but demonstrated conspicuous changes in the posterior and lateral columns at the C2-C7 level, in accordance with the anatomical lesions of the subacute combined degeneration of the spinal cord. In addition to sensori-motor axonal polyneuropathy, multimodal EPs showed abnormal visual EPs with prolonged peak latencies of P100, abnormal brainstem auditory EPs characterized by delayed wave V and difficulty in the recognition of waves I and III, abnormal somatosensory EPs with significant decreased peak amplitudes of cortical potentials bilaterally, and abnormal motor EPs to transcranial magnetic stimulation with prolonged central motor conduction time. CONCLUSION: Our studies document electrophysiological abnormalities that may be attributed to N2O and indicate that N2O may indirectly involve multiple levels of the nervous system. PMID- 17357387 TI - A case of attempted suicide from the ingestion of formalin. AB - The ingestion of formalin causes disorders in the oral cavity, the gastrointestinal tract, liver, kidney, lung, heart, and central nervous system in the early phase of reaction. The stomach suffers the most severe damage in such cases because the formalin is in contact with the gastric mucosa longer than in the other parts of the gastrointestinal tract. Gastric ulcers and mild hemorrhaging are frequently seen. There are no reported cases of gastric perforations in Japan (n= 15), and there are only two reported cases in other countries since 1950 (n = 11). The ingestion of formalin could lead to peritonitis without perforation because of gastric wall inflammation. Cicatrical stricture of the stomach tends to be a major problem in the late phase of formalin ingestion. Similar to our case, seven of twelve reported cases of cicatrical deformity survived without operation. Therefore, a gastrectomy for the cicatrical deformity might not be always indicated if the patients are able to feed themselves sufficiently or if parenteral nutrition can be provided. PMID- 17357388 TI - Acute demyelinating encephalitis after jequirity pea ingestion (Abrus precatorius). AB - INTRODUCTION: Castor and jequirity beans are uncommon causes of poisoning. The more common but less severe castor poisoning is well described, but jequirity bean (Abrus Precatorius) poisoning is rare. The toxicity is attributed to toxalbumins (ricin and abrin) that act by inhibiting protein synthesis. Their use as agents of biological warfare, mechanisms of action, and clinical features of poisoning are summarized. CASE REPORT: A 30-year-old previously healthy female presented with bloody diarrhea and deep coma following ingestion of 3-4 seeds of a plant called 'ratti.' Investigations, including an MRI brain scan, showed evidence of acute demyelinating encephalitis. The patient died three days later due to progressive central nervous system depression. DISCUSSION: This is a previously unreported manifestation of jequirity bean poisoning. Demyelination is immune-mediated, and Abrus is a well-known immuno-modulator and stimulator. A possible immunological pathogenic mechanism is hypothesized. PMID- 17357389 TI - Esophageal obstruction from a hygroscopic pharmacobezoar containing glucomannan. AB - Glucomannan is a dietary fiber that is the main polysaccharide obtained from the tubers of the Amorphophallus konjac plant. It has been used as a dietary fiber for more than 1,000 years in eastern cultures, and has gained popularity in many western countries over the last 20 years. This soluble fiber has very substantial water-holding properties, and forms highly viscous solutions when dissolved in water. It also has considerable hygroscopic properties, expanding rapidly to many times the size of the original material. These properties have made glucomannan an ideal diet agent as the material swells in the GI tract after ingestion, producing a feeling of satiety and fullness. It has also been reported to have hypocholesterolemic, hypoglycemic, hypoinsulinemic and anti-constipatory effects. The negative effects reported include flatulence, abdominal pain, gastrointestinal obstruction, and possible modification of the bioavailability of other medications. This report describes a 37-year-old female who developed delayed esophageal obstruction after ingesting an over-the-counter diet aid containing glucomannan. The patient ultimately cleared the obstruction through forceful emesis, just prior to upper gastrointestinal endoscopy. The patient was noted to have an esophageal web during outpatient endoscopy. This case illustrates the potential dangers of glucomannan and other hygroscopic medications in patients with a history of upper gastrointestinal pathology. PMID- 17357390 TI - Accidental self-administration of epinephrine with an auto-injector. PMID- 17357391 TI - The delphic oracle and the ethylene-intoxication hypothesis. AB - An interdisciplinary team of scientists--including an archeologist, a geologist, a chemist, and a toxicologist--has argued that ethylene intoxication was the probable cause of the High Priestess of Delphi's divinatory (mantic) trances. The claim that the High Priestess of Delphi entered a mantic state because of ethylene intoxication enjoyed widespread reception in specialist academic journals, science magazines, and newspapers. This article uses a similar interdisciplinary approach to show that this hypothesis is implausible since it is based on problematic scientific and textual evidence, as well as a fallacious argument. The main issue raised by this counterargument is not that a particular scientific hypothesis or conjecture turned out to be false. (This is expected in scientific investigation.) Rather, the main issue is that it was a positivist disposition that originally led readers to associate the evidence presented in such a way that it seemed to point to the conclusion, even when the evidence did not support the conclusion. We conclude by observing that positivist dispositions can lead to the acceptance of claims because they have a scientific form, not because they are grounded in robust evidence and sound argument. PMID- 17357392 TI - Plasma alkalinization for acute organophosphorus poisoning--is it a reality in the developing world? PMID- 17357394 TI - [Which are the most influential journals, books and scientists in Latin American biology?]. AB - A survey was distributed by e-mail to 553 biologists who study the Neotropics, in order to identify the journals, books and researchers with the greatest influence over Latin American biology. The biologists' database of the Revista de Biologia Tropical was used to obtain their addresses. One third of them answered. The Revista de Biologia Tropical is considered the most influential journal in the region. The majority of other influential journals are published in developed countries. The thematic distribution of answers, as well as independent assessments found in the literature, indicate that these and other survey results are not biased by the use of the journal's database. By subject, marine and ecological journals are the most influential. In contrast with American science, there are no researchers or books that clearly dominate the field. These results hint to the subjectivity of many awards and qualifications and possibly reflect a lack of tradition regarding appearance of local scientists in the mass media, the small capacity of world wide diffusion for local research and the low priority of science in the Iberoamerican culture. Latin American journals should improve, specially through efficient communication with authors, stringent rejection of inferior manuscripts and through widespread and timely distribution. The marked dominance by male researchers may reflect the lower number of women in the field, and social inequality. Despite the absence of "superstars", there was a correlation: most scientists in the "list of outstanding researchers" were from large countries. The publication of the most influential journal in one of the smallest countries of the region might reflect the relatively long period of existence of the Revista (half a century), the lack of other alternatives in the region and the journal's inclusion in international indices. Recommendations for Latin American science include a selection of the best journals to receive financial support and the establishment, with help from the mass media, of a group of selected researchers as role models for the new generations. PMID- 17357395 TI - [Towards a simple logic in the determination of biological groups: the species and supraspecific groups]. AB - In this paper we discuss about the utility of the species concept as real definition, particularly the Mayr concept. We propose a method for the logical separation of taxa based in the statements of the logical mathematics and the application of the sets theory to the concepts in systematic. We attempt to provide an objective methodology for the interpretation of natural groups in biology including the species as a basic group in evolution. We introduce the concept of the hypothetical ancestor as a mathematical possibility derived from the use of matrix calculations for non square matrix. PMID- 17357396 TI - [A new species of Euglena (Euglenozoa: Euglenales) isolated from extreme environments in "boiling mudflats" of Rincon de la Vieja volcano, Costa Rica]. AB - A new species of euglena isolated from a hot and acid mud pool located in Las Pailas de Barro, Volcan Rincon de la Vieja, Costa Rica is described. This species inhabits hot and acid environments. Euglena pailasensis sp. nov. main features are: the absence of flagella, the presence filaments like "pilis", the presence of chloroplasts with pyrenoids crossed by several tylakoids, and acid and heat tolerance. Molecular phylogeny studies using 18S rDNA and Gap C genes indicated that the new species is related to E. mutabilis. Its taxonomic characters based on morphology, biology and sequence of the 18S rDNA and Gap C genes are discussed and compared with other closely related species of the genus. PMID- 17357397 TI - [Ultrastructural description of Euglena pailasensis (Euglenozoa) from Rincon de la Vieja volcano, Guanacaste, Costa Rica]. AB - The euglenoids are unicellular eukaryotic flagellates living in a diversity of soils and aquatic environments and ecosystems. This study describes the ultrastructure of an euglenoid isolated from the surface of a boiling mud pool with temperatures ranging from 38 to 98 degrees C and pH 2 - 4. The hot mud pool is located in Area de Pailas de Barro, Las Pailas, Rincon de la Vieja Volcano, Guanacaste, Costa Rica. The morphological characterization of the Euglena pailasensis was performed by SEM and TEM. It was determined that, although the euglenoid was obtained from an extreme volcanic environment, the general morphology corresponds to that of a typical member of Euglena of 30-45 microm long and 8-10 microm wide, with membrane, pellicle, chloroplasts, mitochondria, nucleus, pigments and other cytoplasmic organelles. E. pailasensis is delimited by a membrane and by 40 to 90 pellicle strips. It was observed up to 5 elongated chloroplasts per cell. The chloroplast contains several osmiophilic globules and a pyrenoid penetrated by few thylakoid pairs. The nutritious material is reserved in numerous small paramylon grains located at the center of the cell, mitocondria are characterized by the presence of crests in radial disposition toward the interior of the lumen. It was also observed around the external surface "pili" like filaments originating from the pellicle strips. There is no evidence for the presence of flagella in the ampulla (reservoir/canal area), a fact confirmed by negative staining, and a difference regarding other species of Euglena. The observed ultrastructural characteristics are not sufficient to explain the adaptation of this species to acid and hot environments. PMID- 17357398 TI - [In vitro organogenesis in Dalbergia retusa (Papilonaceae)]. AB - Plants were obtained via organogenesis from hypocotyl explants of Dalbergia retusa from in vitro germinated seedlings. Adventitious bud induction was achieved on Murashige and Skoog medium containing five BA (benzyladenine) concentrations. The best BA concentration for budding induction and budding development was 8.8 microM. Shoot rooting was obtained on half-strength modified MS basal medium, supplemented with 20 g x l(-1) of sucrose and five concentrations of indole-3-butyric acid (IBA). The highest number of shoot rooting was obtained with 19.7 microM IBA but the highest average number of roots for plantlet was achieved with 24.6 microM IBA. Plants were transferred to greenhouse conditions. PMID- 17357399 TI - Temporal-spatial distribution of the hermit crab Loxopagurus loxochelis (Decapoda: Diogenidae) from Ubatuba Bay, Sao Paulo State, Brazil. AB - The present work was conducted to determine the distribution of Loxopagurus loxochelis collected monthly, over a period of one year. in Ubatuba Bay (from September/95 to August/96). A total of 179 specimens were collected (138 males, 30 females and 11 ovigerous females). The greatest depth, predominance of very fine sand and highest mean value of organic matter contents of sediment, in combination with the low temperatures registered in winter (July and August), determined the presence of L. loxochelis in the subarea located at the Ubatuba Bay mouth, exposed to the open sea with high water current energy, important because this position insures that spawned larvae will enter into the oceanic circulation. PMID- 17357400 TI - Laboratory spawning of the purple snail Plicopurpura pansa (Gastropoda: Muricidae). AB - The spawning of the muricid gastropod Plicopurpura pansa in the laboratory at 22 23 degrees C is described. Females deposited 1-20 capsules daily for at least 20 weeks, and produced up to 150 capsules each per spawning season. During spawning, egg clusters were formed consisting of hundreds of capsules of different ages deposited by different females. Each egg capsule contained an average of 436 embryos (+/- s.d. 213.6, range: 95-1092, n=50). Embryos developed without nurse eggs. After six to eight weeks of intracapsular, lecithotrophic development, planktotrophic veligers hatched with two fully developed velar lobes. PMID- 17357401 TI - [Distribution patterns and bioerosion of the sea urchin Centrostephanus coronatus (Diadematoida: Diadematidae), at the reef of Playa Blanca, Colombian Pacific]. AB - Regular sea-urchins are one of the main bioeroding organisms affecting coral reefs around the world. The abundance, distribution and bioerosion rate of the sea-urchin Centrostephanus coronatus, were determined in different reef zones of Playa Blanca fringing reef (Gorgona Island, Colombian pacific coast) during 1997 and 1998. The erosion rates were determined calcinating the gut content of the sea-urchins to eliminate all organic components and preserve the inorganic portion of calcium carbonate. C. coronatus showed the highest densities towards the central zones of the reef (plain-crest and front) (12.4 ind/m2; range 0-48 ind/m2). The highest mean bioerosion rate was 0.103 kgCaCO3/m2/yr in the reef plain-crest (0-0.69 kgCaCO3/m2/yr). In the other zones, (back reef and reef front) the mean bioerosion rates were 0.071 (range 0-0.39) and 0.052 (range 0 0.31) kgCaCO3/m2/yr respectively. According to the present data, it can be seen that the destruction of coralline skeletons, produced in this reef by sea-urchins is rather low, compared with the abrasion caused by these organisms in other places of the world. However, the combined action of C. coronatus and other bioeroding organisms (borers and grazers). along with some adverse environmental factors to corals, can be causing a negative balance between normal processes of reef accretion-destruction in Gorgona Island reefs. PMID- 17357402 TI - The genera of Chrysomelinae (Coleoptera: Chrysomelidae) in Costa Rica. AB - Keys in Spanish and English are given for the genera of Chrysomelinae known from Costa Rica. For each genus, a list of species compiled from collections in the University of Costa Rica, the National Biodiversity Institute, and the entomological literature is presented. The genus Planagetes Chevrolat 1843 is recorded for the first time from Central America, and the genus Leptinotarsa Stal 1858 is synonymized with Stilodes Chevrolat 1843. PMID- 17357403 TI - [Oribatid acari (Acari: Oribatei) from Coiba Island National Park, Panama]. AB - Taking part of the Program for The Inventory of Flora and Fauna of Coiba Island National Park (Panama), a first list of oribatid mites (Acari: Oribatei) is presented. Materials studied come from several soil samplings, including humus and fallen leaves, done in Coiba Island in July 1998. 134 species were identified from a total amount of 1053 individuals collected. Almost all the identified species are new records for Panama as well as eigth species that represent first records for the Neotropical Region. A new name is given: Aeroppia mariehammerae n. nom. for Aeroppia sp. and a new combination is proposed: Protoribates antillensis (Mahunka, 1985) n. comb. (Xylobates). PMID- 17357404 TI - A new species of Carabodes (Acariformes: Carabodidae) from Venezuela. AB - A new species, Carabodes venezolanus is described from Venezuela. A comparison with related species and genera is done. PMID- 17357405 TI - [Weight gain of the predator Podisus distinctus (Heteroptera: Pentatomidae) with combinations of the preys Tenebrio molitor (Coleoptera: Tenebrionidae) and Musca domestica (Diptera: Muscidae)]. AB - Little is known about Podisus distinctus (Stal) (Heteroptera: Pentatomidae) one of the Asopinae species with good possibilities for mass rearing and releasing against defoliator caterpillars in eucalyptus reforested areas in Brazil. We evaluated the impact of prey combinations on weight of nymphs and adults of P. distinctus. The prey were Musca domestica L. (Diptera: Muscidae) and Tenebrio molitor L. (Coleoptera: Tenebrionidae). The experiment was developed under 25 +/- 0.5 degrees C, 60 +/- 10% R.H. and photophase of 14 hr, with nymphs of P. distinctus individualized in Petri dishes and fed as: T1-larvae of M. domestica during its whole nymphal phase: T2-larvae of M. domestica during its II instar and of T. molitor during the other instars: T3-larvae of M. domestica during II and III instars and of T. molitor during the other instars: T4-larvae of M. domestica during II, III and IV instars and of T. molitor during the V instar; T5 larvae of T. molitor during all instars. P. distinctus presents lower weight when fed with larvae of M. domestica. For this reason it is recommended to feed P. distinctus with T. molitor during its whole nymphal phase or with larvae of M. domestica only during II and III instars and T. molitor during IV and V instars. PMID- 17357406 TI - Description of the female and male of Mycetarotes carinatus (Hymenoptera: Formicidae). AB - We describe the female and male of the Neotropical fungus-growing ant Mycerarotes carinatus, hitherto only known from type locality, Rio de Janeiro state, Brazil, based on samples of workers. The sexual forms were obtained from a nest maintained in the laboratory. The samples found in Minas Gerais state, expand the geographic distribution of the species. We illustrate the external architecture of the nest of M. carinatus. PMID- 17357407 TI - Are there any agricultural effects on the capture rates of male euglossine bees (Apidae: Euglossini)? AB - During 30 days male euglossine bees were bait-sampled at 12 sites, in the central Pacific coast of Colombia (ten days and four sites at each of three adjacent habitats: farmlands, highly disturbed forest and less disturbed forest) and 487 individuals were captured. Most captured individuals belonged to six species, five widely distributed through the American tropics and an endemic species. Two of the frequently captured species presented no different abundances between habitats, while the other four (67.97% of all the captured individuals), all of them big sized or long-tongued, were more frequently captured at the farmlands. A cluster analysis of the data matrix for the 23 captured species and the 12 sampling sites, grouped together the farmland sites, apart from the forest sites. It is proposed that male euglossine bees from generalist, long-tongued or big sized species, forage frequently at the farmlands, where fragrance or nectar resources may be clumped, less diverse, and present an access restricted by deep corollas or by microclimatic conditions of high temperature and low humidity. PMID- 17357408 TI - [Arthropod collection for biodiversity prospection in the Guanacaste Conservation Area, Costa Rica]. AB - This study describes the results and collection practices for obtaining arthropod samples to be studied as potential sources of new medicines in a bioprospecting effort. From 1994 to 1998, 1800 arthropod samples of 6-10 g were collected in 21 sites of the Area de Conservaci6n Guancaste (A.C.G) in Northwestern Costa Rica. The samples corresponded to 642 species distributed in 21 orders and 95 families. Most of the collections were obtained in the rainy season and in the tropical rainforest and dry forest of the ACG. Samples were obtained from a diversity of arthropod orders: 49.72% of the samples collected corresponded to Lepidoptera, 15.75% to Coleoptera, 13.33% to Hymenoptera, 11.43% to Orthoptera, 6.75% to Hemiptera, 3.20% to Homoptera and 7.89% to other groups. Different life stages per arthropod species were obtained in most samples, 54.26% of them were adults, 19.90% corresponded to larvae, 6.46% to pupae, 6.12% to pre-pupae, 2.07% to nymphs and 3.74% to other stages. Other materials associated to insects like frass represented 11.20% of the samples collected. Several collecting methods were explored, based on the possibility of accessing the necessary amount of material causing the less impact. Most of the samples were obtained by manual collection (44.38%),. followed by insects breeding (25.73%), light traps (18.80%), different types of nets (10.52%) and other methods (0.16%). In general, collecting methods and practices excluded the use of solvents, mixing different species or life stages in the same bag, which might have introduced undesirable effects in the screening systems for new compounds. Based on the possibility of finding new chemicals in similar samples associated to one arthropod species, the collecting strategy included the generation of several samples from same species, separated according to differences in life stages, collecting sites, ecosystems. seasons, feeding materials or behavioral aspects. This strategy allowed the generation a larger number of samples submitted to bioassays in different areas of pharmaceutical research. PMID- 17357409 TI - The reserpine effects on the gonadotrophic cells of the male common carp Cyprinus carpio (Osteichtyes: Cyprinidae). AB - The secretion of gonadotropins (GtH) in goldfish and carp, is stimulated by GtH releasing hormone (GnRH) and is inhibited by dopamine. Studies with antidopaminergics have demonstrated to be effective in order to stimulate the spermiation and the ovulation in different species of teleosts. The reserpine, a drug that deplets the dopamine, has shown to stimulate the spermiation in the common carp. We report here, the effects of reserpine on the number and volume of gonadotrophic cells of the common carp. Eight injections of reserpine alone, at doses of 0.5, 1.0 or 1.5 mg/ml/kg of body weight and at intervals of 48 hours, caused an increase in the number and volume of gonadotrophic cells. The dose 0.5 mg/ml/kg, presented an increase in the number and volume of gonadotrophic cells of 382% and 123%, respectively, above the control group. The dose 1.0 mg/ml/kg, showed an enhanced number and volume of gonadotrophic cells of 704% and 152%, respectively. With the dose 1.5 mg/ml/kg increase in number (171%) and volume (106%) of gonadotrophic cells was lower. The gonads of the experimental groups had an abundance of advanced states of spermatogenesis. Our results show that eight intraperitoneal injections of reserpine were responsible for an increase in gonadodrophic cell, number and volume. PMID- 17357410 TI - General characteristics of the diet of Trachinotus paitensis (Teleostei: Carangidae) from San Ignacio Lagoon, Baja California Sur, Mexico. AB - The food habits of Trachinotus paitensis, in San Ignacio Lagoon B.C.S., Mexico, were investigated. We observed that T. paitensis is carnivorous, feeding mainly on benthic invertebrates (the gastropods Anachis spp., Bittium spp., and the crustacean larvae). We concluded that T. paitensis is an opportunist predator that impacts mainly on epibenthic invertebrates. PMID- 17357411 TI - Reproductive biology of two marine catfishes (Siluriformes, Ariidae) in the Sepetiba Bay, Brazil. AB - Marine catfish are abundant in the Sepetiba Bay, a 305 km2 area in Southeast Brazilian coast (Lat. 22 degrees 54' - 23 degrees 04' S: Long. 43 degrees 44' - 44 degrees 10' W), but the knowledge on their biology is still scanty. The reproductive biology of Sciadeichthys luniscutis (Valenciennes 1840) and Genidens genidens (Valenciennes 1839) was studied through monthly sampling, from October 1998 to September 1999. Fishes were caught with a standardized otter trawl, in the interior of Sepetiba Bay, and near to the confluence with a major freshwater contributor. Six gonadal stages were described, based on macroscopic observations of gonad form, size, weight, color and oocyte diameter, and microscopic observations of differences in size and staining in the nucleus and cytoplasm structures, as viewed through a light microscope. Changes in the gonadosomatic index (GSI) and in stages of gonadal development showed what S. luniscutis spawned in Spring, while G. genidens spawned in Summer. Total spawning was shown for both species as indicated by high concentration of post-ovulatory follicles in spent stages. Fecundity was low (14-38 vitellogenic oocytes for S. luniscutis and 6-24 for G. genidens). when compared with other teleosts. Low fecundity and separation in spawning period suggest that both species are k-strategist, able to avoid interspecific competition in early stages of life cycle to optimize the use of the available niche. PMID- 17357412 TI - [Composition, growth and conditionindex for a population of Poecilia reticulata (Pisces: Poeciliidae), in a pond in Heredia, Costa Rica]. AB - A pond population of Poecilia reticulata was studied in Santo Domingo, Heredia, Costa Rica, between September and November of 1998. The sex ratio was 1:0.49 (males:females). The mean total length was 34.43 +/- 7.26 mm for females, 23.50 +/- 2.24 mm for males and 12.27 +/- 3.41 mm for juveniles. The mean total weight was 0.69 +/- 0.48 g for females: and 0.16 +/- 0.05 g for males and 0.026 +/- 0.027 g for juveniles. The total length-weight relationship for the total population was P= 6 x 10(-5) Lt 3.3272 (r2 = 0.9613). The condition index equation was K = 25.755 e(0.004Lt) (r2 = 0.8925) for females and K = 26.767 e(0.003Lt) (r2 = 0.907) for males. The mean condition index was 31.29 +/- 0.55% for females and 28.52 +/- 0.19% for males. Both sexes reached the sexual maturity when the males and females overcame the 20.00 mm and 23.5 mm of Lt respectively. PMID- 17357413 TI - [Feeding habits of Lutjanus guttatus (Pisces: Lutjanidae) at Los Cobanos and Puerto La Libertad, El Salvador]. AB - Abstract: A total of 175 spotted snapper Lutjanus guttatus were collected monthly in the Los Cobanos and Puerto La Libertad, El Salvador, from January to December 2000 to determine its feeding habits. The fishes studied ranged 9.8 - 58.0 cm in total length. Were collected using push-net and hook and line. This snapper is a bentonic opportunistic carnivorous predator. The total biomass of the stomach contents was 260.5 g. Crustaceans (Squillidae, Portunidae, Dynomenidae. Penaeidae, Sicyoniidae, Callianassidae), were the most abundant group: they accounted for 50.4% of the total biomass. Numerically, Portunus asper was the most abundant prey. Ontogenic differences were observed in the diet. In juveniles (16 cm TL). at any time of the year, the most frequent and abundant components were crustaceans and in adults were crustaceans, fishes and mollusks. The relative importance of different components of the diet was assessed with two indexes that combine. in different ways. percentage frequency of occurrence, percentage number and percentage weight of prey categories. The commercial use this resource and the absence of management strategies are discussed. PMID- 17357414 TI - Gill asymmetry in Labeo ogunensis from Ogun river, Southwest Nigeria. AB - Fluctuating asymmetry (FA), often used as indicator of environmental stress, was evaluated in gill rakers and filaments of Labeo ogunensis from Ogun river, Southwest Nigeria. Mean length and weight of 13.68 +/- 1.28 cm and 59.40+17.48 g were respectively recorded. The gill rakers (t = -0.919) and filaments (t = 1.150) from both sides were not significantly different. The gill filaments recorded (0.31 +/- 2.42) higher incidence of fluctuating asymmetry (FA) compared with the gill rakers (0.21 +/- 1.58), signifying developmental interference in the population. Fish size and sex were observed to exert minimal influence on FA. PMID- 17357415 TI - [Coexistence of Lutjanus peru and Lutjanus guttatus (Pisces: Lutjanidae) in the coast of Guerrero, Mexico: association with the temporal variation of recruitment]. AB - Monthly volumes of capture of Lutjanus peru and Lutjanus guttatus from the coast of Guerrero, Mexico, were analyzed considering eight annual cycles. Time-series, auto correlation, and cross-correlation analysis showed that monthly abundance of populations display unsystematic variations. The FiSAT software was used to obtain the recruitment patterns of both species, using length-frequency data. Our results support the hypothesis that temporal phase-shifts in reproductive events, hence recruitment, explain the coexistence of these species. The outcome of this mechanism is a temporal succession of specific recruit abundance off the coasts of Guerrero, Mexico. The uncoupling of the recruitment events between these species, induces a separation of recruits: therefore, the intake of a particular set of preys could take place at different times. PMID- 17357416 TI - [Diversity, abundance and icthyofaunistic groups of the Chantuto-Panzacola lagoon estuarine system, Chiapas, Mexico]. AB - In the Chantuto-Panzacola system, Chiapas, Mexico, a study of a fish community was carried out between March and November of 1997. From a total of 1456 fish collected, 31 species, 25 genera and 19 families had been identified. The diversity and abundance were high in March with H'= 2.67 bits/ind, D = 3.89 sp/ind, biomass 1.88 g/m2. density 0.25 ind/m2 and average weight 7.55 g/ind. Significant differences were found between the ecological parameters and the environmental variables of the ecosystem in the months of study (ANOVA and Tukey, p < 0.05). The multiple discriminant analysis showed that the temperature and the salinity was the most important factors in the variation of the community. The frequency analysis and spatial distribution of the fish allowed to define fish assemblages formed by several groups of species that inhabits the system. Nine dominant species were defined for the ecosystem, representing the 71% in number and the 76.4% in weight of the total catch, Achirus mazatlanus, Caranx hippos, Cathorops fuerthi, Centropomus robalito, Cichlasoma macracanthum, Cichlasoma trimaculatum, Gobiomorus maculatus, Gobionellus microdon and Lile gracilis. PMID- 17357417 TI - [Trophic structure of the intertidal fish association in the rocky coast of Northern Chile]. AB - The trophic relationships of 13 intertidal fish species collected in northern Chile (20 degrees 18' S and 20 degrees 54' S) from July 1997 to July 1998, the stomach content analysis of 820 specimens, were investigated. The importance of the prey items was assessed by means of gravimetric and frequency of ocurrence methods, together with the Shannon-Wiener (trophic diversity) and Pianka (trophic overlap) indexes. The results allowed to recognize a fish assemblage composed of: 46% of carnivorous species, preying mainly on porcelain crabs. polichaetes and minor crustaceans: 23% of herviborous species, preying mainly on chlorophitic algae: 31% of omnivorous species. preying mainly on chlorophitic algae. Copepoda and Gastropoda. The carnivorous fishes Cheilodactylus variegatus. Helcogrammoides chilensis. Labrisomus philippii and the omnivorous Oplegnatus insignis showed euriphagic tendencies (>2.0 bits), however, the major trophic overlap (>0.90) was observed among herbivorous and omnivorous fishes. Finally, the increase of fish species towards lower latitudes and the increase of herbivory and omnivory levels in the rocky intertidal shore were analyzed. PMID- 17357418 TI - Collection of Dermophis parviceps (Gymnophiona: Caeciliidae) from underground mud nests in Guayacan, Costa Rica. PMID- 17357419 TI - Rediscovery of Hyalinobatrachium chirripoi (Anura: Centrolenidae) in southeastern Costa Rica. AB - The Suretka glass frog, Hyalinobatrachium chirripoi, has been recently rediscovered in the southeastern region of Costa Rica. This species was last reported in Costa Rica in the 1950's. H. chirripoi is distinguished from H. colymbiphyllum, which appears to be its most closely Costa Rican related taxon, by having extensive webbing between fingers II-III. PMID- 17357420 TI - Description of the previously unknown tadpole of Hyalinobatrachium pulveratum (Anura: Centrolenidae). AB - Egg clutches of the centrolenid Hyalinobatrachium pulveratum were sampled in four lowland locations of Costa Rica. The ontogenesis of the tadpoles of this species is documented by periodical descriptions of the larval stages. Larvae of H. pulveratum change their shape during development because of the non-equal growth of some body parts. Due to these changes the larvae in early stages of development differ considerably to those from later stages. Young larvae have a nearly circular cross-section, whereas later larval stages change to a typical flat shape. Some further morphological characteristics like width of the interorbital distance and the oral disk width change but not proportional to larvae length. Numerous measurements on different larval sizes help to recognize the larvae of H. pulveratum in all stages. The striking bright red hyobranchial sinus is the conspicuous characteristic feature ventrally of the hyobranchial apparatus. The use of allometric values for taxonomic and ontogenetic studies is discussed. PMID- 17357421 TI - [Reproductive ecology and hunting of the turtle Tachemys scropta (Testudinata: Emydidae) in the "Momposine Depression", Northern Colombia]. AB - We studied the reproductive ecology of the slider turtle. Trachemys scripta callirostris, during the reproductive season of the year 2000, in an area of the Mompos Depression, northern Colombia. We examined the number of nests ovoposited in locations with different characteristics, their hatching success rates and the natural causes of egg mortality. We also determined the effects of exploitation of nesting females, in two populations with different levels of harvesting. The results showed that the majority of nests were laid along bodies of water, in the first 20 m of the shoreline, in sites with substrates of moderate humidity, sand and clayish texture, covered by creeping vegetation. Invertebrates produced the greatest mortality in the nests. Hatching success was high, compared to other reports for this species. Only in the site with the highest hunting pressure a negative correlation was found, between the harvest rate and the time elapsed since the start of the nesting period, suggesting that the excessive extraction decreased the number of nesting females. Also, the females from the highly exploited site were significantly smaller than those from the less exploited site. The females, neonates and nests of the entire area, exhibited sizes below that reported for other tropical populations of the genus. The continued hunting pressure in northern Colombia, appears to be a factor that has altered the structure and population dynamics of T. scripta callirostris. PMID- 17357422 TI - A new species of Dipsas (Squamata: Colubridae) from Guyana. AB - A new species of Dipsas is described from the Pakaraima Mountains of Guyana. The new species is characterised by 15 dorsal scale rows with the middorsal row slightly enlarged. four pairs of chinshields with the first pair elongate, elongate loreal entering orbit, one preocular, six upper labials, and head narrow anteriorly, increasing in width posteriorly. It could not be determined to which of Peters' (1960) species groups the new species belongs. The new species is known only from 1490 m elevation on Mount Ayanganna. a tepui in the Guiana Shield, where it was found in high-tepui low-canopy habitat, in bromeliads or branches. This is the first record of Dipsas as a member of the Guiana Shield high-tepui herpetofauna. PMID- 17357423 TI - [Mammals of "La Sepultura" Biosphere Reserve, Chiapas, Mexico]. AB - A species list was elaborated for La Sepultura Biosphere Reserve, Chiapas, Mexico. Line transects and direct observations were made. national and international databases were consulted, and animal traces were registered. Animals were captured during the period May 1994 - December 1999. A total of 848 specimen (248 furs and skulls), 32 tracks in plaster, and 9 osseous fragments were collected. A total of 98 species, 70 genera, 29 families, and 10 orders compose the species list. Of these species 87.7% belong to the orders Chiroptera, Rodentia and Carnivora and 21 species were classified according to some kind of legal protection. These data represent a solid and actualized database useful for designing management and conservation plans for this Biosphere Reserve. PMID- 17357424 TI - [Infection of skin fibroblasts in animals with different levels of sensitivity to Leishmania infantum and Leishmania mexicana (Kinetoplastida: Trypanosomatidae)]. AB - Infection and multiplication of Leishmania infantum and L. mexicana inside of skin fibroblasts from hamsters, mice and rats was achieved. This process was demonstrated either by counting parasites inside the stained cells or by electronic microscopy studies. In addition multiplication rate differences in the cells from these rodent species were determined, for L. infantum as well as for L. mexicana. Parasite development in hamsters and mice fibroblasts was evident but there was not multiplication in rat cells showing that apparently they are refractory to Leishmania infection. These results suggest that the parasite affinity for each animal, as well as any intracellular environment resistance, could involve genetic factors in the parasite multiplication. On the other hand, presence of amastigote multiplication inside of parasitophorus vacuole, showed by electronic microscopy images, probes a true parasite transformation. Therefore it is suggested that fibroblasts could work as host cells for parasite survival and permanency in the infected animals. PMID- 17357425 TI - [Diterpenes and other components of Croton hirtus (Euphorbiaceae)]. AB - The roots of Croton hirtus (Euphorbiaceae) collected in Paraiso, Cartago (Costa Rica) afforded, in addition to the few known metabolites, 20 new compounds: the bis-nor dolabradane 1, the dolabradanes 2 and 3, the kauranes 4-7, the cyclopropakauranes 8 and 9, the hirtusanes 10-15, the germacradiene esters 16-18 and the C-25 compound 21, presumably formed by a Diels-Alder reaction between compound 18 and a monoterpene. All structures were elucidated using high field 1D and 2D NMR techniques. MS fragmentation patterns are here reported. The absolute configurations of 4 and 9 were elucidated by using circular dichroism. The separation was performed with modern chromatographic technics. PMID- 17357426 TI - [Activity of acid and alkaline phosphatases (intracellular and extracellular) in rhyzosphere fungi from Arachis hypogaea (Papiloneaceae)]. AB - The potential role of the fungi, isolated from the peanut rhizosphere, in the production of extracellular and intracellular acid and alkaline phosphatase, was evaluated in vitro. Acid and alkaline extracellular phosphatases showed the highest activities, and the Penicillium species were the most efficient in their production. The correlation analysis showed that extracellular acid and intracellular acid phosphatase produced by Aspergillus niger A. terreus, Penicillium sp. y P. brevicompactum were negatively correlated; while the extracellular and intracellular phosphatase activities, were positively correlated. The extracellular acid phosphatase activities produced in vitro by majority of fungi assayed, were not correlated with the acid phosphatase activity present in the peanut soil rhizosphere. Nevertheless, the extracellular alkaline phosphatase activities produced in vitro, were negatively correlated with the extracellular alkaline phosphatase activities present in the rhizosphere. The ability of phosphatase production by fungi isolated from peanut rhizosphere suggests they have great potential to contribute to the P mineralization in this zone. PMID- 17357427 TI - [Composition of fat acids in three Mexican populations of Artemia franciscana from epicontinental waters]. AB - In this paper is presented the percentage of fatty acids composition of three Artemia franciscana Mexican populations of epicontinentals waters; two are from natural environments (Coahuila and San Luis Potosf) and one (Texcoco) is a culture fed with Spirulina. Determination of fatty acids composition in each population, was performed by extraction of total lipid by the soxhlet method and the fatty acids methyl esters were determined by gas chromatography. The results show that Artemia of Texcoco contains the six fatty acids recommended for the culture of fish and crustaceans (16:0; 16:1; 18:1; 18:2w6; 18:3w3 and 20:5w3); Artemia from San Luis Potosi showed the poorest content in these acids and Artemia from Coahuila, although it showed a wide profile, it lacks the linolenic acid. When comparing results among the three populations with ecological data that have been published, it can be pointed out that the environment is decisive for this crustacean; Artemia from Texcoco fed with Spirulina showed the largest variety of fatty acids; the other two populations are wild, and lives in different habitats, Artemia of Coahuila is found in waters that are rich in sulfates and Artemia of San Luis Potosf lives in evaporation saltern ponds, built with stone blocks and therefore with scarce phytoplankton growth. Both Artemia populations showed deficiencies in essential fatty acids, mainly the last one. PMID- 17357428 TI - Role of DNA-PKcs in the bystander effect after low- or high-LET irradiation. AB - PURPOSE: To investigate the role of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in the medium-mediated bystander effect for chromosomal aberrations induced by low-linear energy transfer (LET) X-rays and high-LET heavy ions in normal human fibroblast cells. MATERIALS AND METHODS: The recipient cells were treated for 12 h with conditioned medium, which was harvested from donor cells at 24 h after exposure to 10 Gy of soft X-rays (5 keV/microm) and 20Ne ions (437 keV/microm), followed by analyses of chromosome aberrations in recipient cells with premature chromosome condensation methods. To examine the role of DNA PKcs and nitric oxide (NO), cells were treated with its inhibitor LY294002 (LY) and its scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3 oxide (c-PTIO), respectively. RESULTS: Increased frequency of chromosome aberrations in recipient cells treated with conditioned medium from irradiated but not from un-irradiated donor cells was observed which was independent of radiation type. Bystander induction of chromosome aberrations in recipient cells was mitigated when donor cells were treated with LY before irradiation and with c PTIO after irradiation, and was enhanced when recipient cells were treated with LY before treatment of recipient cells with conditioned medium from irradiated donor cells. CONCLUSION: Irradiated normal human cells secrete NO and other molecules which in turn transmit radiation signals to unirradiated bystander cells, leading to the induction of bystander chromosome aberrations partially repairable by DNA-PKcs-mediated DNA damage repair machinery, such as non homologous end-joining repair pathways. PMID- 17357429 TI - Genetic instability induced by low doses of x-rays in hamster cells. AB - PURPOSE: Genomic instability involves time delayed events and can be manifested as elevated rates of heritable changes in the progeny of irradiated cells. To study the induction of chromosomal instability by very low doses of radiation Chinese Hamster Ovary (CHO) cells were exposed to 10-50 milisieverts (mSv) (approximately 10-50 miligrays (mGy)) of x-rays. MATERIALS AND METHODS: Control and irradiated cell populations were assayed for chromosomal aberrations and assessed using a micronucleus test and anaphase-telophase analysis at the first cell division post-irradiation and at every four population doublings thereafter up to 16 population doublings post-irradiation. RESULTS: Frequencies of micronuclei, anaphase-telophase alterations and chromosomal aberrations were increased when the cells were analysed immediately after x-ray exposure. Micronuclei and anaphase-telophase alterations showed significantly increased frequencies when they were analysed at 12 and 16 population doublings after exposure to 50 mSv. Chromosomal aberrations increased significantly at 12 and 16 population doublings after exposure to 10 mSv and 50 mSv. CONCLUSIONS: Our results are consistent with the presence of a phenomenon by which the initial DNA damage in the surviving cells is memorized. Micronuclei and achromatic lessions were the main cytogenetic damage observed in cells exposed to very low doses of x rays, indicating that these low doses are able to induce genetic instability. PMID- 17357430 TI - Critical role of RecA and RecF proteins in strand break rejoining and maintenance of fidelity of rejoining following gamma-radiation-induced damage to pMTa4 DNA in E. coli. AB - PURPOSE: This study was undertaken to understand the roles of RecA and RecF proteins in strand break rejoining and maintenance of fidelity of the process following exposure of E. coli to gamma-radiation in vivo. MATERIALS AND METHODS: A plasmid DNA construct, pMTa4, was transformed into isogenic repair proficient (wild) and deficient (recF and recA) E. coli strains and gamma-irradiated up to 30 Gy in vivo. The plasmid DNA was isolated under repair non-permissive (R-)and permissive (R+) conditions and analyzed by gel electrophoresis for the yields of single strand breaks (SSB) and double strand breaks (DSB) and their repair. The clonogenic survival of the E. coli was also recorded. The effects of gamma irradiation on recA reconstituted with cell free extract of wild strain or ultra violet (UV)-irradiation were also monitored. RESULTS: None of the strains used in this investigation showed effects of radiation-induced oxidative base damage. The dose dependent increase in SSB and DSB on pMTa4 in wild and recF mutants in R- condition were abolished upon repair incubation. The recA mutant exhibited a disturbed yield of SSB and DSB along with formation of gamma-radiation-induced 'ladder'. The 'ladder' was not observed after repair incubation, UV-irradiation or gamma-irradiation in presence of cell-free extract of wild strain. The survival of recA mutants was seriously compromised. CONCLUSIONS: Wild, recF and recA strains of E. coli could repair gamma-irradiation-induced oxidative damage to base or nucleotide (NT) in vivo. In absence of either RecA or RecF proteins, efficiency of rejoining of strand went down; RecA proteins seemed more critical than RecF in this. High fidelity or correct rejoining of strand breaks, on the other hand, seemed to require simultaneous presence of both RecA and RecF proteins. PMID- 17357431 TI - Comparison of the effects of enriched uranium and 137-cesium on the behaviour of rats after chronic exposure. AB - PURPOSE: A radionuclide that accumulates in the central nervous system is likely to exert both a chemical and a radiological effect. The present study aimed at assessing the behavioral effect of two radionuclides previously shown to accumulate in the central nervous system after chronic exposure--uranium and cesium. MATERIALS AND METHODS: Rats were exposed for 9 months to drinking water contaminated with either enriched uranium at a dosage of 40 mg U x l(-1) or 137 cesium at a dosage of 6500 Bq x l(-1), which correspond to the highest concentrations measured in some wells in the south of Finland (uranium) or in the milk in Belarus in the year following the Chernobyl accident (137-cesium). RESULTS: At this level of exposure, 137-cesium had no effect on the locomotor activity measured in an open-field, on immobility time in a forced swimming test, on spontaneous alternation in a Y-maze and on novel object exploration in an object recognition test. Enriched uranium exposure specifically reduced the spontaneous alternation measured in the Y-maze after 3 and 9 months exposure although it did not affect the other parameters. CONCLUSION: Enriched uranium exposure altered the spatial working memory capacities and this effect was correlated with previously described accumulation of uranium in the hippocampus which is one of the cerebral areas involved in this memory system. PMID- 17357432 TI - Can radiation-induced apoptosis be modulated by inhibitors of energy metabolism? AB - PURPOSE: To determine the effect of the inhibitors of energy metabolism, 2 deoxyglucose (2DG) and sodium azide, on radiation-induced apoptosis. MATERIALS AND METHODS: Radiation-induced apoptosis was determined in U937 monocytic leukaemia cells exposed to energy inhibitors post-irradiation. Apoptosis was scored microscopically using morphological criteria. Glycolysis was determined by assessing glucose consumption and lactate production. Adenine nucleotide levels were measured using a luciferase assay after enzymatic conversion to ATP. Respiration was measured using a Clark-type oxygen electrode. RESULTS: In addition to their apoptosis-inducing properties, both 2DG and azide modified post irradiation apoptosis. 2DG induced apoptotic radiosensitization after exposure to lower concentrations (5 mM, 10 mM) up to 20 h post-irradiation while a level of radioprotection was found after 5 h exposure to higher doses up to 100 mM. By contrast, all doses of azide examined (5-50 mM) induced apoptotic radioprotection at all times examined. Glycolytic flux and ATP levels fell rapidly with increasing 2DG dose but energy charge remained unchanged. Glycolysis was less influenced by azide, with ATP levels being initially maintained after exposure but decreasing in a dose-dependent manner at 3 h post-irradiation. However, energy charge was unaffected by azide at the concentrations examined. CONCLUSIONS: Both 2DG and azide can influence radiation-induced apoptosis possibly through their effects on glycolysis and ATP levels. We suggest that modulation of energy metabolism provides mechanistic insight into radiation induced apoptotic pathways. PMID- 17357433 TI - Adaptive response and human benefit: Part I. A microdosimetry dose-dependent model. AB - PURPOSE: It is important to evaluate how adaptive response may be of human benefit from the risks of ionizing radiation. The purpose of this work is to develop and apply a microdosimetric dose response model capable of explicitly determining, for broad beam exposures, the threshold and progressive activation of natural spontaneous and radiation damage protective mechanisms associated with adaptive response and other cellular negative response behavior. MATERIALS AND METHODS: A biophysical model was developed quantifying the accumulation of Poisson distributed microdose specific energy hits to cell critical nucleus volumes. The model was applied to the adaptive response data of Wiencke et al., Redpath et al., Azzam et al. and Pohl-Ruling et al. The model was also applied to non-adaptive response data showing dose response reductions below the zero dose natural spontaneous level and to data exhibiting mid-range non-monotonic dose response plateaus. RESULTS: We find good fits of the model to all data. For adaptive response, a significant result is, that only one or two specific energy hits of low linear energy transfer (LET) radiation in the cell nucleus activates the protective mechanisms for both the natural spontaneous and radiation damage. Several data support a dose plateau for radon progeny alpha production of chromosome aberrations in human lymphocytes. Using the model, a bystander factor of about 30 is obtained with the model for high dose rate, in vitro alpha particle data. For low dose rate in vivo, the bystander effect is minimal suggesting for alphas that the bystander effect may be dose rate dependent. There is no evidence of bystander effects in the low LET adaptive response data analysis. CONCLUSIONS: The microdosimetry model allows concise determinations of specific energy hits within the cell critical nucleus volume to activate both protective and damage mechanisms. One or two low LET hits can result in reduction of both zero dose natural spontaneous and radiation-induced, carcinogenic causing damage. The model should be useful in comparing in vitro and in vivo broad beam to single track microbeam exposure data. The model is capable of determining, to an accuracy of +/- one specific energy hit, the minimum threshold for induction of radioprotective mechanisms--crucial to assessing the potential human benefit of adaptive response and other negative dose response behavior. PMID- 17357434 TI - A dose-survival model for low energy ion irradiation. AB - PURPOSE: To explain the dose survival data for low energy ion irradiation in bioorganisms. MATERIAL AND METHODS: Applying DNA target theory and considering physical processes of low energy ion radiation, a mathematical dose-survival model was derived to analyze the data of low energy ion irradiation of bioorganisms. RESULTS: The survival fraction S of bioorganisms after a dose D of low energy ion irradiation was: The analysis showed that survival fraction of bioorganisms under low energy ion irradiation can be well fitted with this formula. CONCLUSIONS: It was shown that the dose-survival effects of low energy ion irradiation in bioorganisms were related to the physical processes of low energy ion irradiation and repair effects that can be explained by momentum transfer processes occurring with low energy ion irradiation. PMID- 17357435 TI - Is chromosome radiosensitivity and apoptotic response to irradiation correlated with cancer susceptibility? AB - PURPOSE: Individuals who have been treated for breast cancer have been reported to have increased lymphocyte chromosomal sensitivity to ionizing radiation and a significantly lower apoptotic response to irradiation compared to controls. We set out to test these findings using a substantial number of cases sampled before treatment (which could alter the parameters measured), compared to age-matched controls with normal mammograms. MATERIAL AND METHODS: We used the G2 chromosome breakage, and apoptotic response assays of peripheral blood lymphocytes to ionizing radiation to compare 211 unselected newly diagnosed and untreated breast cancer patients, with 170 age, sex and ethnically matched controls. RESULTS: We found no significant differences between breast cancer patients and their matched controls in the G2 assay or apoptotic response. However, there was some evidence that both cases and controls with a strong family history of breast cancer had higher radiosensitivity than those without. CONCLUSIONS: This is the largest and best controlled study of its kind, but it has not replicated previous reports of differences between chromosome breakage or apoptotic response in breast cancer cases vs. controls. However there was a suggestion of increased radiosensitivity in patients with a strong family history, which may indicate a heritable cancer susceptibility trait, warranting further study. PMID- 17357436 TI - Modifications of the radiosensitivity of a renal cancer cell line as a consequence of stable TIMP-1 overexpression. AB - PURPOSE: To investigate the potential effects of stable tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) overexpression on DNA damage and cell killing following low-dose gamma-radiation and whether this up-regulation interfered with the activation of the matrix metalloproteinase -2 (MMP-2) and -9 (MMP-9) in a highly metastatic renal carcinoma cell line. MATERIALS AND METHODS: Stable transfections were carried out using the cytomegalovirus expression plasmid pRc/CMV carrying TIMP-1 cDNA and LIPOFECTAMINE reagent. TIMP-1 expression in selected clones was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. Exponentially growing Caki-1 cells were treated with sub lethal doses of ionizing radiation (0- 10Gy) either alone or following stable TIMP-1 transfection. DNA damage was assessed by the Alkaline Comet Assay and cell survival was determined by a clonogenic assay. Caki-1 cell cycle alterations following TIMP-1 transfection were assessed by fluorescence activated cell sorting (FACS) analysis of propidium iodide (PI)-stained cells. The interactions between TIMP-1 and MMP-2 and MMP-9 were analysed 24 hours post irradiation by means of gelatin zymography. RESULTS: Three clones with varying degrees of TIMP-1 expression were selected and used for further analysis. TIMP-1 transfected Caki-1 cells displayed significantly higher mean tail moment values (p < 0.05) following irradiation at doses between 5 and 10 Gy relative to that seen with radiation alone. The TIMP-1 radiosensitizing effect was accompanied by large decreases in the survival fraction of the parental Caki-1 cell line and significant increases in the alpha-parameter of the linear-quadratic fit. These effects were directly correlated to the degree of TIMP-1 gene expression detected in the selected clones. Interestingly, elevated levels of TIMP-2 protein were detected in the three TIMP-1 clones compared to TIMP-2 levels present in Caki-l cells. The three clones also displayed marked phenotypic alterations relative to their parental cell line. Significant increases in the percentage of cells arrested in the G2/M phase of the cell cycle were detected in the three clones under normal growth conditions and reduced serum conditions (p < 0.05). When the TIMP-1 clones were assessed for their MMP-2 activity, a marked decrease in the MMP-2 mean protein levels was detected in clone T1-3 following irradiation at doses between 2 and 6 Grays (Gy) (p < 0.01) and clone T1-2 at 2- 5Gy (p < 0.05). MMP-9 activity was differentially affected by ionizing radiation in the three TIMP-1 clones. T1-3 and TI-2 displayed significantly reduced MMP-9 levels at various dose points whereas T1-1 exhibited elevated levels of MMP-9 activity at higher doses of treatment (p < 0.05). CONCLUSION: These results demonstrate a dual role for the TIMP-1 overexpression in this renal carcinoma cell line, both as radiosensitizing agents and effectors of MMP-2 and MMP-9 activity. PMID- 17357437 TI - The incorporation of the concept of minimum RBE (RbEmin) into the linear quadratic model and the potential for improved radiobiological analysis of high LET treatments. AB - PURPOSE: The formulation of relative biological effectiveness (RBE) for high linear energy transfer (high-LET) radiation treatments is revisited. The effects of changed production of sub-lethal damage with varying LET is now considered via the RBEmin concept, where RBEmin represents the lower limit to which RBE tends at high doses per fraction. MATERIALS AND METHODS: An existing linear-quadratic formulation for calculating RBE variations with fractional dose for high-LET radiations is modified to incorporate the twin concepts of RBEmax (which represents the value of RBE at an effective dose-per-fraction of 0 Gy) and RBEmin. RESULTS: Fits of the model to data showed RBEmin values in the range of 0.1- 2.27. In all cases the raw data was a better statistical fit to the model which included RBEmin, although this was only very highly significant in one case. In the case of the mouse oesophagus it is shown that, if change in the beta radiosensitivity coefficient with LET is considered as trivial, an underestimation > 5% in RBE can be expected at X-ray doses of 2 Gy/fraction if RBEmin is not considered. To ensure that the results were not biased by the statistical method used to obtain the parameter values relevant to this analysis (i.e., using fraction-size effect or Fe-plots), an alternative method was used which provided very similar correlation with the data. CONCLUSIONS: If the production of sublethal damage is considered independent of LET, there will be a risk that non-corrected evaluation of RBE will lead to an over- or under-estimate of RBE at low doses per fractions (the clinically relevant region). PMID- 17357438 TI - Comparison of the combined action of oxaliplatin or cisplatin and radiation in cervical and lung cancer cells. AB - BACKGROUND AND PURPOSE: To test the combined effects of oxaliplatin and radiation versus cisplatin and radiation using human cervical and lung cancer cell lines. MATERIAL AND METHODS: CaSki cervical cancer cells, and A549 lung cancer cells were cultured under standard conditions. Cells were treated with escalating doses of gamma-irradiation (0-6 Gy), and with oxali- and cisplatin for 2 h or 24 h, or a combination of both. Cell survival was measured by a colony-forming assay. Survival curves were fitted to the data using the linear quadratic model. Sensitizer enhancement ratios (SER) were calculated at the 37% survival level, and isobologram analysis was applied to test for the drug-radiation interactions. RESULTS: Oxaliplatin as well as cisplatin alone were cytotoxic in both cell lines. In CaSki cells, oxaliplatin and cisplatin significantly increased radiation toxicity. In A549 cells no increase of radiation toxicity was observed after treatment with cisplatin, however, isobologram analysis revealed supra additive interaction between oxaliplatin and radiation in A549 cells. CONCLUSION: Oxaliplatin had the same effectiveness on tumor cells as cisplatin and induced enhanced radiation toxicity in lung cancer cells, where cisplatin was not able to achieve radiosensitization. PMID- 17357439 TI - Orientation behaviour of Pagrus major larvae exposed to UV-B radiation in laboratory conditions. AB - PURPOSE: The increasing intensity of ultraviolet-B (UV-B) radiation is a potential threat to the aquatic environment. The recognition capacity of the aquatic animals may help them to avoid this harmful radiation. The response of individual species, especially during early development may help to understand the vulnerability of that species and its potentiality in natural fishery. MATERIALS AND METHODS: The orientation behaviour of red sea bream Pagrus major larvae exposed to UV-B radiation (280-315 nm) was studied within the laboratory (1.41 W/m(2)) under following experimental conditions: (i) two fluorescent lamps fixed above the tank, (ii) one fluorescent lamp on the left side, one fluorescent lamp and one UV-B lamp on the right side, and (iii) one UV-B lamp and one fluorescent lamp on the left side, one fluorescent lamp on the right side of the tank. RESULTS: In the first treatment, 7- and 20-day-old larvae were significantly (p < 0.0095) higher in number at the right side than left and middle regions of the tank. Some 33-60% of larvae were found in the middle region of the tank at the age of 30-32 days. In the second treatment, significantly (p 5 0.0034) lower numbers of larvae (10-13.3%) were found in the middle region of the tank compared to the other sides between days 17 and 20, whereas 40- 86.67% larvae were found in the middle region between days 25 and 36. In the third treatment, significantly (p < 0.015) higher numbers of larvae were found in the right side at the age of days 17-25 and in the middle region between days 32 and 36. CONCLUSIONS: This study showed that UV-B sensitivity of P. major developed during ontogenic development. Care should be taken at early stages. PMID- 17357440 TI - Response to high LET radiation 12C (LET, 295 keV/microm) in M5 cells, a radio resistant cell strain derived from Chinese hamster V79 cells. AB - PURPOSE: To study the effects of 12C-beam of 295 keV/microm (57.24 MeV) on M5 and Chinese hamster V79 cells by using cytogenetic assays like micronuclei (MN) induction, chromosomal aberrations (CA) and apoptosis. Additionally, the relative survival of these two cell lines was tested by the colony forming ability of the cells, with a view to understanding the mechanism of cellular damages that lead to difference in cell survival. MATERIALS AND METHODS: Confluent cells were irradiated with 12C-beam at various doses using 15UD Pelletron accelerator. Cell survival was studied by the colony forming ability of cells. MN assay was done by fluorescent staining. Different types of chromosomal aberrations in metaphase cells were scored at 12 h after irradiation. Apoptosis was measured at different post irradiation times as detected by nuclear fragmentation and DNA ladder was prepared after 48 h of incubation. RESULTS: Dose-dependent decrease in surviving fractions was found in both the cell lines. However, the surviving fractions were higher in M5 cells in comparison to V79 cells when exposed to the same radiation doses. On the other hand, induced MN frequencies, CA frequencies and apoptosis percentages were less in M5 cells than V79 cells. Very good correlations between surviving fractions and induced MN frequencies or induced total CA or induced apoptosis percentages were obtained in this study. CONCLUSIONS: The cell strain M5 showed relatively more radio-resistance to 12C-beam compared to Chinese hamster V79 cells in this study. As the MN formation, CA and apoptosis induction were less in M5 cells as compared to parental V79 cells, the higher cell survival in the former could possibly be attributed to their better repairing ability leading to higher cell survival. PMID- 17357441 TI - Vulnerability of folate in plasma and bone marrow to total body irradiation in mice. AB - PURPOSE: To examine how folate status in a body is influenced by oxidative stress. MATERIAL AND METHODS: Mice were given total body irradiation (TBI) by X ray, and changes in the concentration of folate were compared to those in vitamins C and E. RESULTS: In a time-dependent study, folate in plasma and bone marrow decreased from 5 h until 120 h post-TBI at 3 Gy. Folate in plasma and bone marrow decreased in a dose-dependent manner at 24 h. Marked decreases of vitamins C and E were also detected in bone marrow, but not in plasma even at 10 Gy of TBI. The susceptibility of plasma folate by irradiation was confirmed by an in vitro exposure study. Neither vitamins C and E nor folate were decreased in the liver by TBI. CONCLUSION: It is suggested that folate is vulnerable to oxidative stress, and folate may need to be evaluated, particularly for TBI or radiotherapy. PMID- 17357442 TI - Consensus development guidelines for the role of LMWHs in the management of unstable coronary artery disease: an Indian perspective. PMID- 17357443 TI - [Studies of dynamic distribution of Thr11-phosphorylated H3 in MCF-7 at mitosis]. AB - The phosphorylations of histone H3 on Ser10, Ser28, Thrll and Thr3 of the amino terminal are the events that related to mitosis of the cell. To study the function of Thrll phosphorylation of histone H3,indirect immunofluorescence labeling and laser confocal were employed with the antibody that was specific for Thrll-phosphorylated histone H3. The celluar dynamic distribution of this protein was examined at mitosis in MCF-7 cell. Our results showed that Thrll- phosphorylation of H3 initiated at centromere at early prophase in MCF-7 cells. The fluorescence signal on Thr1l-phorphoslated histone H3 reached the strongest at early metaphase at the centromere punctated in the central of mitotic cell. The dephosphorylation of Thrll-phorphoslated histone H3 was completed in anaphase. The behavior of Thrll phosphorylation and dephosphorylation in mitotic cell of MCF-7 were different from that of Ser10 phorphorylation and dephosphorylation. The results suggest that the Thrll phosphorylation of histone H3 has a specific function in mitosis different from Ser10 phosphorylation. There was a precise spatial and temporal correlation between H3 phosphorylation of Thrll and initial stages of chromatin condensation. Thrll -phorphoslated histone H3 located on centromeres suggest that it maybe included in the active kinetochore during mitosis. PMID- 17357444 TI - [Cadmium induced apoptosis of HEK293 cells and its mitochondrial apoptosis pathway]. AB - HEK293 cell was chose to study the kidney damage of cadmium and to explore the significance of caspase 3,Bcl-2 and AIF (apoptosis inducing factor) in the apoptosis of cells induced by cadmium. Inhibition of the cell proliferation was measured by MTT assay. The structure of apoptotic cells was observed by light microscopy and electron microscopy; moreover, apoptotic cells were detected by DNA electrophoresis, flow cytometry and confocal laser microscopy. Furthermore,the expressions of Pro-caspase-3, Bcl-2 and the location of AIF in cells (mitochondria,cytoplasm or nuclei) were tested by western blot and immunofluorescence assay. CdCl2 exhibited anti-proliferative activity in dosage and time-dependent manner. DNA ladders of HEK293 cells were showed on agarose gel electrophoresis and the fragments of DNA were integral of 180-200 bp. 6-9 hours after 30 micromol/L CdCl2 treatment,DNA ladders were distinct. However, mistiness DNA ladder or smear was found when HEK293 cells were treated with CdCl2 on higher concentration or treated longer. It suggests that necrosis may happen, and flow cytometry results confirmed it. Morphological examination showed cell shrinkage, chromosomal condensation, karyotheca margination, nucleus cracking, vacuoles formed in cytoplasm and the presence of apoptotic bodies. At the same time,mitochondrial membrane potential (MMP) decreased, and the expression of Pro caspase-3, Bcl-2 were decreased in time-dependent manner. Furthermore, AIF was released from mitochondria,and then traveled to nuclei. It suggests that CdCl2 may induce the apoptosis of HEK293 cells involving mitochondrial disruption including AIF migration and Cyt c release through both caspase-independent and dependent pathways, and Bcl-2 and Caspase-3 are important factors which participate in the processes. PMID- 17357445 TI - [The pathogenic mechanism of homocysteine -induced endothelial nitric oxide synthase dysfunction and the antagonistic effects by folic acid]. AB - To investigate the pathogenic mechanism of homocysteine-induced endothelial nitric oxide synthase dysfunction and the antagonistic effects by folic acid (FA). Human umbilical vein endothelial cells (HUVEC)were cultured to the third generation. Then HUVEC were cultured with Hcy at different concentrations (0,10,30,100 and 300 micromol/L),with or without FA(100 micromol/L)for 72 hours. The mRNA and protein levels of endothelial nitric oxide synthase (eNOS) were analyzed by RT-PCR and immunohistochemistry respectively. Asymmetric dimethylarginine (ADMA)was measured by reversed-phase high performance liquid chromatography. The dimethylarginine dimethylaminohydrolase(DDAH), activity of eNOS and the production of NO were analyzed simulta- neously. After HUVEC were exposed to Hcy at different concentrations for 72 hours, the level of eNOS mRNA and the content of eNOS protein, the eNOS activity, and the production of nitric oxide (NO) were all significantly and dose-dependently reduced compared with the control group (P< 0.05). The activity of DDAH has a parallel decrease and the ADMA concentration showed a cor- responding increase. The addition of folic acid (100 micromol/L)resulted in partial antagonistic effects against the injury of Hcy on NOS system of endothelial cells, the eNOS protein level and eNOS activity, and NO production increased,and so does the DDAH activity,and the ADMA concentration reduced. But the FA didn't influence the eNOS mRNA expression. The pathogenic mechanism of homocysteine-induced eNOS dysfunction may involve two levels,the level of eNOS protein and eNOS activity,and the level of the expression of eNOS gene. The injury on the level of eNOS protein and eNOS activity may go through the DDAH-ADMA pathway. Folic acid can exert partial protective roles against the Hcy in the level of eNOS protein and eNOS activity,but without impact on the expression of eNOS gene. PMID- 17357446 TI - [Study on the type, distribution, development and secreting activity of mucous cells in the intestine tract of catfish (Silurus asotus)]. AB - The type and distribution of mucous cells stained with AB & PAS (pHAB=2.6) in the intestine tract of silurus asotus (body length 16.4-21.0cm, body weight 33.6 64.3g) have been studied. The development and secreting activity of mucous cells have been investigated using scanning and transmission electron microscopy. The results showed that the mucous cells were dark blue,weak blue and cambridge blue in colour after being stained with AB & PAS(pHAB=2.6); it mainly contained acid mucopolysaccharides; the mucous cells had 3 shapes i.e. capsule-shaped, pear shaped and cup-shaped. The capsule-shaped mucous cells were distributed in the bottom of the epithelia of the intestine, and its diameter was about 4.40 microm. The pear-shaped mucous cells were distributed in the middle-layer of the epithelia of the intestine, and its vertical range and sidelong was about 6.00 microm and 3.40 microm respectively. The cup-shaped mucous cells were distributed in the top of the epithelia of the intestine, and its vertical range and sidelong was about 12.00 microm and 4.60 microm respectively. The density of mucous cells presented an increasing trend from the anterior(low) to posterior(high) and middle(higher) segment. After derived from bottom cells, the mucous cells evolved gradually from fundus film to exterior of mucous membrane. The mucous cells in developing were filled with plenty of big and small mucosity particulates, and the secreting method of mucous cells was peak serosity secretion. PMID- 17357447 TI - Study on powdery mildew resistance transfer from S. cereale L.cv. Weiling rye into wheat. AB - Weiling rye (S. cereale L.cv.), a Chinese dwarf rye, confers high powdery mildew (Erysiphe gramininis f.sp.tritici) in China. My8443, a wheat cultivars infecting seriously powdery mildew disease, was used as the female parent and Weiling rye was used as the donor of powdery mildew resistance in the study. A new wheat-rye translocation line,named No.147,was developed from BC2F6 progenies of wheat cultivars My8443 and Weiling rye to transfer the resistance from Weiling rye to common wheat. The powdery mildew resistance of No.147 and its parents were investigated in seedling and adult stages by artificially inoculating the mixture of advanced pathogenic races in room and field and the single pathogenic race in room. Improved Giemsa C-banding technique and genomic in situ hybridization (GISH,Genomic in situ hybridization) were used to identify wheat and rye chromosomes. Acid polyacylamide gel electrophoresis(APAGE) separation of endosperm gliadin and simple sequence repeat(SSR) PCR amplification of 11 SCM Secale cereale markers also were employed for 1RS confirmation in the study. The results showed that No.147 was a new 1BL/1RS wheat-rye chromosome translocation with high powdery mildew resistance derived from Weiling rye. The reason on the formation of the new wheat-rye chromosome translocation was analyzed. The utilizations of resistance gene resource derived from Chinese Weiling rye and the new 1BL/1RS translocation line in wheat genetics and breeding improvement were discussed in the paper. PMID- 17357448 TI - [Genetic variations among populations of Ageratina adenophora from different areas, investigated by inter-simple sequence repeat markers]. AB - Crofton weed, Ageratina adenophora,a troublesome weed in the world,is an invasive organism in China. Genetic diversity of thirty-two Chinese populations of A. adenophora from different areas was analyzed with the inter-simple sequence repeat (ISSR) technique. It indicated that its genetic diversity was rich. Nei's gene diversity and Shannon's information index were 0.235 and 0.372 at species level respectively. Genetic variation of Crofton weed mainly existed in the population, and about 34.5% of the total variance was attributable to population divergence and 65.5% to individual differences within populations. The Mantel Z statistic test showed that the genetic distance between populations generally increased with geographic distance (r=0.542,p< 0.001),which indicated that isolation by distance is one of the blocks of gene flow of A. adenophora. Genetic diversity level of Crofton weed had the trend to decrease along with the increased altitude (r=0.368,P<0.001), and the mean of Nei's gene diversity and Shannon's diversity indices both decreased with the increased altitude. PMID- 17357449 TI - [The development of secondary cells in the callus of Hypericum perforatum L. and hypericins accumulation]. AB - Hypericum perforatum L. is a kind of traditional herbal medicine that has been used as an anti-depression medicine in Europe for centuries. One of its biological active compound, hypericins, is stored in the special secondary structure,black nodules,which located in the stems, leaves and flowers. Most researches focus on the development of the black nodules in vivo and how to culture the plant to produce more hypericins. We studied the process of de differentiation from explants to callus and the pathway of hypericins biosynthesis in callus and cells of H. perforatum L. which reflected the relationship between the cell development and secondary metabolites accumulation. The morphogenesis of cells development and hypericins accumulation were studied by electron microscopy and histological technologies. Hypericins began to accumulate in a bunch of secondary cells located on the surface of the callus in late development period. Hypericins initially produced in the cytoplasm and were transported into the vacuole and then accumulated. E.R. took apart in the process of hypericins production. Theses results supplied the gap of hypericins production and accumulation in vitro and gave some useful information regarding mass-production hypericins by tissue and cell culture technology. PMID- 17357450 TI - [Modulation of cyclosporin a on the expression of MMP-9 AND MMP-2 of the first trimester human trophoblast cells]. AB - The aim of this study was to explore whether cyclosporine A (CsA) can modulate expression of MMP-9 and MMP-2 and invasion of the first-trimester human trophoblast cells. The invasive ability of the trophoblast cells modulated by CsA was observed by Matrigel invasion assay. The effect of CsA on the transcription and translation of MMP-9 and MMP-2 was determined by Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Gelatin Zymography. In-cell Western was used to detect the level of phospho-ERK1/2 of trophoblast cells treated with CsA. We found that CsA(1.0 micromol/L) could remarkably promote the invasive ability of the first-trimester human trophoblast cells; CsA(1.0 micromol/L) could also induce the expression of MMP-9 and MMP-2 at transcriptional and translational level; U0126,a MEK inhibitor,could obviously inhibit the enhanced invasion and expression of MMP-9 and MMP-2 of these cells induced by CsA; CsA (1.0 micromol/L) could activate the ERKl/2 in a time-dependent manner. These results above indicate that CsA can induce the expression of MMP-9 and MMP-2 through activating MAPK/ERK1/2, which contributes to the improved invasion of the first-trimester human trophoblast cells. PMID- 17357451 TI - [The distribution of ATPase during the pollen development of Allium cepa L]. AB - The distribution of ATPase in pollen of Allium cepa L. was studied using Pb3 precipitation technique during pollen development. Only some ATPase precipitates were located in the nucleus of microspore mother cells (MMC) and a few in its cytoplasm. After meiosis of MMC,many ATPase precipitates appeared in the exine of pollen wall of microspore even it was in tetrad, suggesting that ATPase from tapetum is necessary during pollen wall construction. The intine of pollen wall of microspore was synthesized at its late stage and consisted of cellular material which was from microspore. There were also many ATPase precipitates in intine,and the ATPase came from microspore. Then ATPase precipitates in vegetative cell increased and that in generative cell decreased during the development of 2-cellular pollen,suggesting the differentiation of vigor between both cells. The physiological functions of ATPase in developing pollen of Allium cepa L. were analyzed. PMID- 17357452 TI - [Comparisons among different methods of culturing neural stem cells isolated from human fetal cortex]. AB - Neural stem cells (NSCs) are proved to be promising cell sources for gene therapy and cell therapy. To pursue optimal conditions for the isolation and culture of neural stem cells residing in human fetal cortex,the cortical tissue was dissociated mechanically and digested with various enzymes. Short-term trypsin digestion combined with pipette dissociation proved to be the suitable method of isolating human NSCs derived from the fetal cortex. Furthermore,DMEM/F12 medium was superior to the neurobasal medium in the aspect of clonal formation. In repeated dissociation experiments,it was found that accutase, instead of trypsin,endowed the NSCs with better growth and efficient neurosphere formation. PMID- 17357453 TI - [The changes in chloroplast proteome caused by different nuclear background in cytoplasmic male-sterile (CMS) of wheat]. AB - Comparative studies of chloroplast proteome on different developmental stage (seeding, tillering, shooting, booting stage) of leaves have been made in isoplamic allonuclear male-sterile lines Nongda 3237A, Xiaoyan No.6 A and their maintainer lines by 2D-PAGE. The results indicated that no obvious differences were found in chloroplast proteome between Nongda 3237A, Nongda 3237B, Xiaoyan No.6A, Xiaoyan No.6B at different developmental stages of leaves. Differences were found just at booting stage in Xiaoyan No.6A and its maintainer lines. Obvious differences, however, were observed in chloroplast proteome between isoplasmic allonuclear male-sterile lines Nongda 3237A and Xiaoyan No.6A. For instance,2 protein spots (pl5.4/34kDa, pl5.4/32kDa) at seedling stage,6 protein spots (pl5.4/80kDa, pl5.4/65kDa, pl5.4/60kDa, pl5.4/48kDa, pI5.4/40kDa, pI5.4/35kDa) at booting stage were present in Xiaoyan No.6A and absent in Nongda 3237A. pl6.3/18kDa was present at seedling stage in Nongda 3237A and absent in Xiaoyan No. 6A. pI6.8/28kDa protein spot revealed the developmental changes. It was present in leaves at seedling, tillering, shooting stages and absent at flowering stage in Nongda 3237A. No development changes of the protein spot were observed in Xiaoyan No.6A. These experiment results demonstrated that it was possible chloroplast proteome wasn't relative to the cytoplasmic male-sterile characteristics. But nuclear background in male -sterile lines can obviously affect chloroplast protein composition. Distant relative on nuclear-cytoplasmic has larger differences on chloroplast proteome than close relative on nuclear cytoplasmic in CMS. PMID- 17357454 TI - [Research on cell affinity of poly-L-lactide/porcine-derived xenogeneic bone composite in vitro]. AB - OBJECTIVE: To evaluate the feasibility of poly-L-lactide(PLLA)/porcine-derived xenogeneic bone (PDXB) composite as a scaffold for the bone tissue engineering. METHODS: The film and the scaffold of the PLLA-PDXB composite were respectively prepared by a solution casting method and a solution casting-particle leaching method. The composite film and scaffold were further treated by the surface alkaline hydrolysis. The surface morphology of the composite was observed by the scanning electron microscopy, and hydrophilicity degree of the composite was measured. The OCT-1 osteoblast-like cells were cultured and amplified in vitro as the seeding cells, which were then implanted on the film and scaffold. The adherence rate, adherence shape,proliferating activity, and growing morphology of the OCT-1 osteoblast-like cells were observed on the film. RESULTS: The PDXB particle 50 microm in diameter on average had a similar phase structure to that of hydroxyapatite. But its Ca/P ratio was lower than that of hydroxyapatite. After the surface alkaline hydrolysis, the PDXB particle could be exposed on the surface of the PLLA-PDXB composite. The surface roughness and hydrophilicity of the PLLA-PDXB composite were obviously enhanced. The cell adherence rate and the cell proliferation activity of the PLLA-PDXB composite were higher than those of the pure PLLA material. The cells tended to grow on the exposed surface of the PDXB particles. The cells seeded on the composite scaffold could migrate to the inside of the composite scaffold and grew well. CONCLUSION: The PLLA-PDXB composite has a good cell affinity, and this kind of composite can hopefully become a new scaffold material to be used in the bone tissue engineering. PMID- 17357455 TI - [Spinal fusion of lumbar intertransverse process by using tissue engineered bone with xenogeneic deproteinized cancellous bone as scaffold]. AB - OBJECTIVE: To study the properties of the xenogeneic deproteinized cancellous bone used as a scaffold in the bone tissue engineering and its application to the spinal fusion of the lumbar intertransverse process in a goat. METHODS: The deproteinized bone was derived from an adult pig's femoral cancellous bone through the physical and chemical treatments. Its morphological features, constituting components, and biomechanical properties were examined by the scanning electron microscopy, X-ray diffraction analysis, and mechanical experimental instrument. The cell-material complex was observed under the inverted phase contrast microscope to evaluate the adhesion and the growth of the osteoblasts. The experimental model of the spinal fusion of the lumbar intertransverse process was produced in 12 male goats aged 6-8 months, which were divided into two groups. In Group A, the tissue engineered bone constructed by the xenogeneic deproteinized cancellous bone, the recombinant human bone morphogenetic protein 2, and the mesenchymal stem cells was used for the spinal fusion; however, in Group B the auto-ilium was used. The samples were harvested at 4, 8 and 12 weeks postoperatively, and a series of examinations were performed, including the radiography and the histomorphological assay. RESULTS: The deproteinized cancellous bone had a natural pore network system, with an aperture ranging in size from 200 to 500 microm, containing a main organic material of collagen and the inorganic material of hydroxyapatite. So, the deproteinized cancellous bone had a good mechanical strength and a good histocompatibility. In Group A, the X-ray examination at different timepoints postoperatively showed that at 4 weeks, the bridging areas of all the fusion sites were not clear, especially on the internal side; at 8 weeks, the upper and lower bridged parts had a narrowed gap, with formation of much continuous bony callus; at 12 weeks, a complete fusion occurred. In the early stage, the material density was slightly lower in Group A than in Group B, but at 12 weeks the density was almost the same in both the groups. Histological examination in the transplant area showed that at 4 weeks in Group A there was a new bone formation in a multipoint way; at 8 weeks, a "sandwich-shaped" new bone was crossed with the transplanting materials; and at 12 weeks, a medullary cavity was remodeled and a new cancellous bone was formed. The osteogenic process of the tissue engineered bone constructed by the xenogeneic deproteinized cancellous bone scaffold was almost the same as the auto-ilium osteogenesis. CONCLUSION: The xenogeneic deproteinized cancellous bone is a good material in the bone tissue engineering, which can be used as an osteogenesis scaffold and provide a stable environment for revascularization and osteoblastic differentiation. PMID- 17357456 TI - [A study on nano-hydroxyapatite-chitosan scaffold for bone tissue engineering]. AB - OBJECTIVE: To fabricate a nano-hydroxyapatite-chitosan (nano-HA-CS) scaffold with high porosity by a simple and effective technique and to evaluate the physical and chemical properties and the cytocompatibility of the composite scaffold. METHODS: The three-dimensional nano-HA-CS scaffolds with high porosity were prepared by the in situ hybridization-freeze-drying method. The microscopic morphology and components of the composite scaffolds were analyzed by the scanning electron microscopy (SEM), the transmission electron microscopy (TEM), the X-ray diffraction(XRD)examination, and the Fourier transformed infrared spectroscopy (FTIR). The calvarial osteoblasts were isolated from the neonatal Wistar rats. The serial subcultured cells (3rd passage) were respectively seeded onto the nano-HA-CS scaffold and the CS scaffold, and then were co-cultured for 2, 4, 6 and 8 hours. At each time point, four specimens from each matrix were taken to determine the cell-adhesion rate. The cell morphology was observed by the histological staining and SEM. RESULTS: The macroporous nano-HA-CS scaffolds had a feature of high porosity with a pore diameter from 100 to 500 microm (mostly 400-500 microm). The scaffolds had a high interval porosity; however, the interval porosity was obviously decreased and the scaffold density was increased with an increase in the contents of CS and HA. The SEM and TEM results showed that the nano-sized HA was synthesized and was distributed on the pore walls homogeneously and continuously. The XRD and FTIR results showed that the HA crystals were carbonate-substituded and not well-crystallized. The cytocompatibility test showed that the seeded osteoblasts could adhere the scaffolds, proliferating and producing the extracellular matrix on the scaffolds. The adherence rate for the nano-HA-CS scaffolds was obviously higher than that for the pure CS scaffolds. CONCLUSION: The nano-HA-CS scaffolds fabricated by the in situ hybridization-freeze-drying method have a good physical and chemical properties and a good cytocompatibility; therefore, this kind of scaffolds may be successfully used in the bone tissue engineering. PMID- 17357457 TI - [Differentiation of adipose-derived stem cells induced by recombinant adenovirus's containing fibers derived from B-group serotype 35-mediated bone morphogenetic protein]. AB - OBJECTIVE: To investigate the differentiation of the adipose-derived adult stem cell (ADASC) induced by the recombinant adenovirus's containing fibers derived from B-group serotype 35 (rAd5/F35)-mediated human bone morphogenetic protein 7 (hBMP-7) gene and to explore a new cell source for the bone tissue engineering. METHODS: The hBMP-7 gene was amplified with the pcDNA1.1/AMP-hBMP-7 plasmid as a formwork. After the purification, the gene fragment was cloned into the pDC316 carrier for the recombination of the plasmid of pDC316-hBMP-7. The 293 cells were co-transfected by the skeleton plasmid of pBHG-fiber5/35 and the shuttle plasmid of pDC316-hBMP-7, and the recombinant plasmid of Ad5/F35-hBMP-7 was obtained; the recombinant plasmid of Ad5/ F35-enhancd green fluorescent protein(EGFP) was obtained by the similar method. The rat ADASCs were cultured and transfected by the Ad5/F35-hBMP-7 plasmid and the Ad5/F35-EGFP plasmid, respectively; the remaining untransfected ADASC were used as the controls. The morphology and the growth pattern of the transfected cells were evaluated. The transcription and the expression of the transfected genes and the steogenic phenotypes such as calcium nodules and osteocalcin were evaluated by ELISA. RESULTS: The identification of PCR and enzyme cutting showed that the construction of the recombinant Ad5/F35 hBMP-7 plasmid could be confirmed. The transfection rate of the ADASC by the Ad5/F35-EGFP plasmid was determined to be greater than 90%. The hBMP-7 gene in the transfected ADASC could express the corresponding protein, and the formation of the calcium nodules could be found in the induced group. The electron microscopy showed that there was a calcium element in the cytoplasm, the alkaline phosphatase result was positive, and the expression of osteocalcin was increased. CONCLUSION: The rAd5/F35-hBMP-7 gene can promote the differentiation of the adipose-derived adult stem cells to the osteoblasts in the bone tissue engineering. PMID- 17357458 TI - [Changes in peripheral blood T lymphocyte subsets of rabbits in early stage after transplantation of tissue engineered bone constituted by biologically-derived scaffold]. AB - OBJECTIVE: To observe the changes in the peripheral blood T lymphocyte subsets and the histomorphology of the transplanted tissues in the rabbits in the early stage after transplantation of the tissue engineered bone constituted by the biologically-derived scaffold and to confirm the feasibility of the biologically derived materials as a scaffold in the bone tissue engineering. METHODS: Forty eight healthy New Zealand rabbits (weight, 2. 0-2.5 kg) with a 1-cm defect were equally and randomly divided into 4 groups: Groups A-D. The partial demineralized freeze-dried bone (PDFDB), the tissue engineered bone constructed by the osteoblasts derived from the lactant rabbit periosteum as a seeding cell, the xenogeneic cancellous bone undergoing the antigen self-digestion, partial demineralization and freeze-dried process as a scaffold, and the fresh xenogeneic allografting bone were respectively transplanted into the segmental defects of the rabbit radii in Groups A-D. To examine the effects of the 4 different materials, the flow cytometry was used to observe the changes in the T lymphocyte subsets in the rabbit peripheral blood at 1, 2, and 4 weeks after the operations and to examine the osteogenesis achieved by the 4 materials, the histological observations were also performed at 2, 4, 8, and 12 weeks after the operations. RESULTS: Two weeks after the tissue engineered bone transplantation in Group B, the osteoblasts and chondroblasts were found in the apertures of the scaffold, the new bone formation could be observed, the osteoclasts could be seen in the peripheral zone, and some of the netlike frameworks were destroyed and absorbed. Four weeks after the operation, the histological observation revealed that the osteocartilagionous callus turned into a woven bone. The peripheral blood T lymphocyte subsets of CD4+ and CD8+ were significantly greater in number 1-2 weeks after the operations and in Groups A and B than before the operations and in the other groups (P<0. 05);4 weeks after the operations the T lymphocyte subset of CD4+ was only slightly greater in number than before the operations, but with no statistically significant difference (P>0.05). In Group C, the increase of the T lymphocyte subsets of CD4+ and CD8+ was not significant after the operation (P>0.05). The T lymphocyte subsets of CD4+ and CD8+ were significantly greater in number 1, 2 and 4 weeks after the operations and in Group D than before the operation and in the other groups (P<0.05). CONCLUSION: The tissue engineered bone constructed by the partial demineralized freeze-dried bone as a scaffold does not cause a serious immunologic rejection in the early stage after the transplantation and does not affect its good ability to repair the bone defect. The biologically-derived bone can be used as a scaffold in the bone tissue engineering. PMID- 17357459 TI - [Fabrication of porous poly lactic acid-bone matrix gelatin composite bioactive material and its osteoinductive activity]. AB - OBJECTIVE: To fabricate a novel porous bioactive composite biomaterial consisting of poly lactic acid (PLA)-bone matrix gelatin (BMG) by using the supercritical carbon dioxide fluid technique (SC-CO2) and to evaluate its osteoinductive activity. METHODS: The cortical bones selected from healthy adult donors were processed into BMG by the defatting, demineralizing, and deproteinizing processes. PLA and BMG were mixed at a volume radio of 3 : 1; then, the PLA-BMG mixed material and the pure PLA material were respectively placed in the supercritical carbon dioxide reaction kettles, and were respectively added by the NaCl particles 100-200 microm in diameter for the porosity of the materials so that the porous PLA-BMG composite material and the porous PLA composite material could be formed. The mouse osteoblast-like MC3T3-E1 cells were cultured in the dulbecco's modified eagle medium (DMEM) supplemented with 10% fetal bovine serum. Then, 20 microl of the MC3T3-E1 cell suspensions containing 2 X 10(6) cells /ml were delivered into the culturing plate (24 wells/plate) made of the different materials, which were co-cultured for 2 weeks. In the PLA-BMG group, 100 microg of the crushed PLA-BMG material was contained in each well; in the PLA group, 100 microg of the crushed PLA material was contained in each well; and in the DMEM group, only DMEM was contained, which served as the control group. There were 6 wells in each group. The quantitative analysis on the calcification area was performed by the staining of the alizarin red S. The co-cultured cells were harvested and lysated in 1 ml of 0. 2% Nonidet P-40 by the ultrasonic lysating technique. Then, the ALP activity and the Ca content were measured according to the illuminations of the reagent kits. RESULTS: The porous PLA-BMG composite material showed a good homological porosity with a pore diameter of 50-150 microm and a good connectivity between the pores. The ALP activity, the Ca content, and the calcification area were significantly greater in the PLA-BMG group than in the PLA group and the control group (325.59 +/- 70.40 U/gprot, 3.51+/- 1.64 mmol/gprot, 42.98 +/- 4.44% vs. 63. 62 +/- 30.01 U/gprot, 1.04+/-0.21 mmol/gprot, 9.55+/-1.94%, and 2.40+/-1.47 U/gprot, 0.70+/-0.24 mmol/gprot, 0.86+/-0.41%; P<0.05). Meanwhile, there was a statistically significant difference between the PLA group and the control group in the ALP activity and the calcification area (P< 0.05). CONCLUSION: The porous PLA-BMG composite material prepared by the use of SC-CO2 has a good osteoinductive activity and can be used as a promising bone biomaterial and a bone tissue engineered scaffold. PMID- 17357460 TI - [Effects of recombinant human bone morphogenetic protein 2 and osteogenic agents on proliferation and differentiation of rat mesenchymal stem cells]. AB - OBJECTIVE: To investigate the effects of the recombinant human bone morphogenetic protein 2 (rhBMP-2) and/or the osteogenic agents on proliferation and expression of the osteoblast phenotype differentiation of the SD rat mesenchymal stem cells (MSCs). METHODS: The rat MSCs were cultured in vitro and were randomly divided into the experimental groups (Groups A-I) and the control group. In the experimental group, MSCs were induced by rhBMP-2 in different doses (10, 50, 100 and 200 microg/L) in Groups B-E, the osteogenic agent alone (Group A) and by the combined use of rhBMP-2 [in different doses (10,50, 100 and 200 microg/L)] and the osteogenic agent in Groups F-I. The MTT colorimetric assay was used to evaluate the proliferation, and the activities of alkaline phosphatase (ALP) and osteocalcin (OC) were observed at 3, 6, 9, 12 days, respectively. RESULTS: The inverted phase contrast microscopy showed that MSCs by primary culture for 12 hours were adhibited, with a fusiform shape at 48 hours. At 4 days they were polygonal or atractoid, and were spread gyrately or radiately at 6 days. At 10 days, they were spread at the bottom of the bottle. The statistical analysis showed that the expression of the osteoblast phenotype differentiation of MSCs could be induced in the experimental groups. The proliferation of MSCs could be enhanced in a dose-dependent manner in Groups B-E. The expression of the osteoblast phenotype differentiation, which was tested by the activities of ALP and OC, was significantly higher in Groups F-I than in Groups A-E. CONCLUSION: The combined use of rhBMP-2 and the osteogenic agents can enhance the MSC proliferation and induce an expression and maintenance of the osteoblast phenotype differentiation of the rat MSCs. PMID- 17357461 TI - [Effects of implanted myoblasts with soluble carriers on severely-cryodamaged tibialis anterior muscles]. AB - OBJECTIVE: To investigate whether the implanted myoblasts with the soluble carriers can improve the repairing efficiency for the severely-cryodamaged tibialis anterior muscles. METHODS: The skeletal myoblasts were isolated from the newborn SD rats by the use of the enzyme digestion. They were purified and serially subcultivated; the subcultivated myoblasts of the 3rd generation were marked with BrdU. The severely-cryodamaged tibialis anterior muscle models were established from 84 SD rats aged 5 months. They were randomly divided into 4 groups, including Group A1 (the implanted myoblasts with the carriers-F12 containing 0.1% sodium hyaluronate), Group A2 (the implanted myoblasts, with the carriers-F12 that did not contain 0.1% sodium hyaluronate), Group B1 (the implanted carrier solution containing 0.1% sodium hyaluronate, but with no myoblasts), and Group B2 (with no carrier solution or myoblasts). Six rats were killed at the following time points: at 2, 5 and 9 days, and 2, 4, 8 and 12 weeks after operation; the immunohistochemical and the Mallory staining studies were performed for an evaluation on the repairing efficiency for the severely cryodamaged tibialis anterior muscles. By the imaging analysis, the number of the survived cells in each group was compared at 2 days, and the area ratio of the collagen fiber in each group was also compared at 8 weeks. RESULTS: The BrdU immunohistochemical staining showed that the number of the remaining implanted cells was significantly greater in Groups A1 than in Group A2, the migrating area of the myoblasts was greater, the distribution of the cells was more uniform, the cell differentiating potential was undestroyed, the repairing efficiency for the severely-cryodamaged tibialis anterior muscles was significantly improved. There was no blue-stained nucleus at each time point in Group B. The Mallory staining showed that the fibrous degeneration in the tissue repairing process was significantly inhibited in Groups A1, A2 and B1; the inhibition was most obvious in Group A1, and next in Group A2. The imaging analysis indicated that at 2 days after operation, the number of the survived cells was significantly greater in Group A1 than in Group A2 (P<0.05). At 8 weeks after operation, the collagen fiber was the least in Group A1, less in Group A2, more in Group B1, and the most in Group B2 (P<0.05). CONCLUSION: The implanted myoblasts can significantly improve the repairing efficiency for the severely-cryodamaged muscle tissues, and the implanted carrier solution containing 0.1% sodium hyaluronate can improve the implanting efficiency for the myoblasts. PMID- 17357462 TI - [Comparison between effects of small intestinal submucosa graft and inside-out vein graft on repairing peripheral nerve defects]. AB - OBJECTIVE: To make a comparison between the effects of the small intestinal submucosa (SIS) graft and the inside-out vein graft on repairing the peripheral nerve defects. METHODS: SIS was harvested from the fresh jejunum of the quarantined pig by curetting the musoca, the tunica serosa, and the myometrium; then, SIS was sterilized, dried and frozen before use. Thirty-six male SD rats were divided into 3 groups randomly, with 12 rats in each group. Firstly, the 10 mm defects in the right sciatic nerves were made in the rats and were respectively repaired with the SIS graft (Group A), the inside-out autologous vein graft (Group B), and the auto-nerve graft (Group C). At 6 weeks and 12 weeks after the operations, the right sciatic nerves were taken out, and the comparative evaluation was made on the repairing effects by the histological examination, the neural electrophysiological examination, the computerized imaging analysis, and the Trueblue retrograde fluorescence trace. RESULTS: The histological examination showed that the regenerated nerve fibers were seen across the defects in the three groups at 6 weeks after the operations. The nerve fibers were denser, the formed nerve myelin was more regular, and the fibrous tissue was less in Group A than in Group B; the nerve regeneration was more similar between Group A and Group C. At 12 weeks after the operations, the neural electrophysiological examination showed that the neural conductive rate was significantly lower in Group B than in Groups A and C (P<0.05), but no statistically significant difference was found between Group A and Group C (P > 0.05); the component potential wave amplitude was not statistically different between Group A and Group B; however, the amplitude was significantly lower in Groups A and B than in Group C (P < 0.05). At 6 weeks and 12 weeks after the operations, the computerized imaging analyses showed that the axis-cylinder quantity per area and the nerve-tissue percentage were significantly greater in Group A than in Group B (P < 0.05); the average diameter of the regenerated axis cylinder, the axis-cylinder quantity per area, and the nerve-tissue percentage were significantly lesser in Group B than in Group C (P < 0.05). At 12 weeks after the operations, the Trueblue retrograde fluorescence trace revealed that the positively-labeled neurons were found in the lumbar 3-6 dorsal root ganglion sections in the three groups. CONCLUSION: The small intestinal submucosa graft is superior to the autologous inside-out vein graft in repairing the peripheral nerve defects and it is close to the auto-nerve graft in bridging the peripheral nerve defects. Therefore, the small intestinal submucosa is a promising biological material used to replace the auto-nerve graft. PMID- 17357463 TI - [Preparation of carboxymethylchitin and studies on its properties]. AB - OBJECTIVE: To prepare carboxymethylchitin and study its properties. METHODS: Chitin was prepared from fresh shrimp shells and then carboxymethylchitin was prepared by the methods of alkalization and etherification as well as by the purification technique. The deacetylation degree of carboxymethylchitin was determined by the double-jump potentiometric titration method; the substitution degree was determined by the element analysis method; the carboxymethyl substitution position was analyzed by the Fourier transform infrared spectroscopy apparatus and the nuclear magnetic resonance spectroscopy apparatus; the relative molecular weight and its polydispersity were determined by the gel permeation chromatography with the multiple angle laser light scattering detection; the biological properties were tested according to the GB/T 16886 biological evaluation on medical devices. RESULTS: Carboxymethylchitin could be prepared by alkalization and etherification from chitin which was prepared from fresh shrimp shells by decalcification and deproteinization. The deacetylation degree of carboxymethylchitin was 13.76% according to the double-jump potentiometric titration; the degrees of deacetylation and substitution were 14.53% and 1.2390 respectively according to the element analysis. The IR spectrum showed that the substitutive position was N, O-substitution, and the 13C-NMR spectrum showed that substitutive position of carboxymethylchitin was mostly primary substitution of 6 OH, and according to the substitutive proportion, the substitutive turns were in the following decreasing order: 6-OH, NH2, and 3-OH. The weight-averaged and the number-averaged molecular weights and polydispersity were 6. 25 x 10(5), 5.60 x 10(5) and 1.22, respectively. The results from the biological property test showed that carboxymethylchitin was a biomaterial that was sterile, pyrogen-free, acute toxicity-free, cytotoxicity-free, intracutaneous irritation-free, skin sensitization-free and biomaterial genotoxicity-free, with no side or adverse effects on the related tissues after implantation into the human body. CONCLUSION: Carboxymethylchitin prepared from chitin by alkalization and etherification is a macromolecule biomaterial that has a low degree of deacetylation, a high degree of substitution, and a good biocompatibility. PMID- 17357464 TI - [An experimental research of tissue engineered submandibular gland cells growing on collagen sponge scaffold]. AB - OBJECTIVE: To make an experimental research of the tissue engineered rat submandibular glands (SMG) cells growing on a collagen sponge scaffold under an optimal culture condition. METHODS: The Wistar rat (8 days old) SMG cells of the second generation were seeded on the surface of the collagen sponge scaffold (5 mm X 5 mm x 2 mm) and were cultured under a physiologically optimal condition for 3 weeks. At 1, 2 and 3 weeks, the cultured cells were observed on their shapes and structures by the histological examination and the scanning electron microscopy. The cultured cells underwent the immunohistochemistry research (the cytokratin 8.13, CK8. 13; alpha-smooth muscular actin, alpha-SMA) staining performed at 3 weeks of the culture, and the amylase activity analysis (the Amano method) performed at 1 day, 1, 2 and 3 weeks of the culture for an evaluation on the secretion function of the cells; the ultrastructures of the cells were also observed by the transmission electron microscopy for an identification of their origins. RESULTS: The observation under the scanning electron microscope showed that at 1 week after the cell-seeding, the seeded cells were attached to the collagen sponge scaffold surface, with no cell process formed; at 2 weeks the cells increased, with formation of the cell process that was anchored on the collagen sponge scaffold surface; and at 3 weeks, the scaffold surface-attached cells increased, with formation of the filiform fibers in the surface layer of the cells. The immunohistochemistry staining showed that the cultured epithelial cells of SMG were strongly positive for the specific antibody of CK8. 13, and the myoepithelial cells were positive for the specific antibody of alpha-SMA. The transmission electron microscopy showed that in the surface layer of the cultured epithelial cells of SMG the microvilli, plasm crease, and zymogen granules were observed, with a big and oval-shaped nucleus in the cell, and mitochondria and rough endoplasmic reticulum in the cytoplasm of the cell. The amount of amylase secreted by the cells cultured with the collagen sponge scaffolds increased at a different degree with an extension of the culturing time. CONCLUSION: The collagen sponge has a satisfactory cell compatibility, and the SMG cells cultured with this kind of collagen sponge can keep their abilities of proliferation and differentiation and their function of secretion. Therefore, this kind of cultured SMG cells can be used as the tissue-engineered cells seeded in the scaffold. PMID- 17357465 TI - [Development of periodontal tissue engineering]. AB - OBJECTIVE: To review the literature about the development of the periodontal tissue engineering. METHODS: Based on an extensive review of the latest literature concerned, we analyzed and evaluated the method of the periodontal tissue engineering. RESULTS: The development of the periodontal tissue engineering in the fields of the seed cells, modifier genes, cell factors, and scaffold materials provided a brand-new thinking and method for complete regeneration of the periodontal tissues. CONCLUSION: The periodontal tissue engineering has an excellent future but many problems still require a further study and a satisfactory solution. PMID- 17357466 TI - [Effects of growth factors on periodontal ligament cells]. AB - OBJECTIVE: To evaluate the effects of the polypeptide growth factors on the periodontal ligament cell (PDLC) based on a comprehensive review on the literature concerned. METHODS: The recent literature related to the effects of the polypeptide growth factors on the PDLC were extensively and comprehensively reviewed and a corresponding evaluation was made. RESULTS: The proliferation and the multi-directional differentiation of the PDLC were found to be the basis for the regeneration of the periodontal tissues. The effects of the polypeptide growth factors on the function of the PDLC became a hot issue of the research on the regeneration of the periodontal tissues. The polypeptide growth factors were found to play an important role in the migration, growth, proliferation, differentiation, and synthesis of protein and matrix of the PDLC. CONCLUSION: The polypeptide growth factors can be used in the periodontal regeneration treatment, but a further research is still required to improve this kind of treatment. PMID- 17357467 TI - [Intestinal stem cells and tissue engineering technique used in treating intestinal diseases]. AB - OBJECTIVE: To review the development of researches on the stem cells and the tissue engineering technique used in the intestines. METHODS: We comprehensively reviewed the literature related to the stem cells and the tissue engineering technique used in the intestines, and summarized the conclusions made by the researches concerned. RESULTS: The researches on the stem cells and the tissue engineering technique used in the intestines were attractive topics in the recent years and obtained some developments, especially in the field dealing with the characteristics, proliferation and differentiation of the intestinal stem cells as well as the tissue engineering framework of the small intestinal submucosa in vivo. However, the markers for the differentiation of the intestinal stem cells were still a critical problem, which had not been solved yet, and besides, the researches on the intestinal tissue engineering were still in the initial stage. CONCLUSION: There is a broad prospective application of the intestinal stem cells and the tissue engineering technique to the intestinal problem solution. Substantial achievements can be obtained in the treatment of the inflammatory bowel disease, in an exploration on the oncogenesis mechanism, and in the clinical application of the intestinal tissue engineering. PMID- 17357468 TI - [Development of research on liver stem cell and its future application]. AB - OBJECTIVE: To investigate the research development of the liver stem cell (LSC) and to predict its future application. METHODS: Based on our own researches and combined with the review of the related literature at home and abroad, we analyzed and evaluated the latest development of the research on the LSC. RESULTS: We knew the differentiation and proliferation of the LSC towards some kinds of specified cells were affected by many factors; and the researches on the LSC in regard to its activation, isolating culture, bolting, and evaluation still needed further improvements. CONCLUSION: With the development of the research, the liver stem cell can become a new seed cell to cure some liver diseases. PMID- 17357469 TI - [Development of liver stem cell transplantation for liver regenerative treatment]. AB - OBJECTIVE: To review the development of the liver stem cell transplant for the liver regenerative treatment. METHODS: The transplantation-related articles about the stem cell classification, repairing mechanisms, administration routes, and existing problems in the liver regenerative therapies reported in the latest literature were extensively reviewed. RESULTS: The related liver-repairing stem cells were found to be inside and outside the liver, i. e. , the hepatic stem cells and the non-hepatic stem cells. They could repair the liver by the mechanism of the cell fusion or the cell transdifferentiation. The stem cells could be administrated via the portal vein. However, the application of the liver stem cell transplant was restricted by many related clinical problems. CONCLUSION: Further studies are still needed for an improvement of the clinical feasibility for the stem cell transplantation, especially for the liver stem cell transplantation. PMID- 17357470 TI - [Self-renewal signaling pathway and culture system in vitro of embryonic stem cells]. AB - OBJECTIVE: To review the latest development of the research on the self-renwal signaling pathway and culture system in vitro of the embryonic stem cells (ESCs). METHODS: The recent articles about the self-renewal signaling pathway and culture system in vitro of the ESCs were extensively reviewed. RESULTS: Understanding of the molecular mechanism of the self-renewal in vitro and pluripotency of the ESCs was considered important for developing improved methods of deriving, culturing and differentiating these cells into the cells that could be successfully used in the clinical practice. CONCLUSION: A further research is needed to elucidate the self-renewal signaling pathway and the pluripotency of the ESCs and the culture system in vitro for the human ESCs remains to be further improved and developed. PMID- 17357471 TI - Development of therapy for Duchenne muscular dystrophy. AB - OBJECTIVE: To review and summarize the latest development of the therapy for the Duchenne muscular dystrophy (DMD). METHODS: The recently-published articles related to the therapies for DMD were extensively reviewed and briefly summarized. RESULTS: The therapeutic approaches for DMD included the gene therapy, the cell therapy, and the pharmacological therapy. The gene therapy and the cell therapy were focused on the treatment for the cause of DMD by the delivery of the missing gene, the modification of the mutated gene, and the transfer of the normal cells including the stem cells, while the pharmacological therapy dealt with the downstream events caused by the dystrophin gene defect, slowed down the pathologic progress of DMD, and improved the DMD patient's life quality and life span, by medication and other factor treatments. CONCLUSION: There is still no cure for DMD because of various difficulties in replacing or repairing the defected gene and of the multifaceted nature of the severe symptoms. Therefore, it is imperative for us to find out a more effective treatment that can solve these problems. PMID- 17357472 TI - [Treatment of brain ischemic stroke by co-transplantation of neural stem cells and endothelial progenitor cells]. AB - OBJECTIVE: To discuss the feasibility of treating the brain ischemic stroke by the co-transplantation of the neural stem cells(NSCs) and the endothelial progenitor cells(EPCs). METHODS: The original biomedical articles concerned with the treatment of the brain ischemic therapy by the use of the NSCs and the EPCs were extensively reviewed as well as retrieved and analyzed. RESULTS: The review revealed that the NSCs and the EPCs could migrate to the injured area due to brain ischemic stroke, the environment of the local microcirculation could induce the neurogenesis and the vasculogenesis to repair the injury, and the neurogenesis and vasculogenesis could promote each other. CONCLUSION: The co transplantation of the NSCs and the EPCs can represent a new promising strategy for more effectively solving the two difficult problems of the neural cell loss and the vascular obstruction caused by the brain ischemic stroke. PMID- 17357473 TI - Do omega-3 fatty acids help in depression? AB - There is an increasing number of studies assessing whether omega-3 fatty acids play a role in behavioural and mood disorders, particularly depression. Findings of this research have been highlighted in the media, and in recent reports by the Mental Health Foundation and the food charity Sustain. As a result of such raising of awareness, patients might ask their GPs and mental health professionals about taking omega-3 fatty acids as a treatment for depression. Here we assess whether omega-3 fatty acids have a role in the management of such individuals. PMID- 17357474 TI - Stable angina--who needs revascularisation? AB - In the UK, about 5% of men and 3% of women have, or have had, angina. Also, estimates suggest that, each year, around 340,000 people present with the symptom for the first time. Characterised by pain or discomfort in the chest, angina is usually caused by atherosclerotic coronary artery disease and so carries an increased risk of cardiovascular complications such as myocardial infarction and death from coronary heart disease (CHD). In stable angina, the symptoms are induced by exertion, reflecting the limitation of blood supply through the narrowed arteries and the resulting myocardial ischaemia. The condition is not only potentially distressing, but may also limit daily function and quality of life. To address these problems and the elevated cardiovascular risk, standard management includes lifestyle measures (e.g. physical activity without excessive exertion, stopping smoking, weight control); tackling other cardiovascular risk factors (e.g. raised blood pressure, diabetes mellitus); and medication to control angina (e.g. nitrates, beta-blockers, calcium antagonists) and to reduce overall cardiovascular risk (e.g. aspirin, statin therapy). Where such non invasive measures alone are inadequate, revascularisation (restoration of adequate blood supply to the heart muscle) by using coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) may also be needed. Here we discuss methods for, and difficulties in, assessing patients who present with suspected stable angina to identify those who could benefit from revascularisation. PMID- 17357475 TI - Comparison of properties of tumor necrosis factor-alpha converting enzyme (TACE) and some matrix metalloproteases (MMPs) in catalytic domains. AB - The crystal structural data of TACE, MMP-1, MMP-2, MMP-3 and MMP-9 were obtained from PDB database, and then their catalytic domains' properties including conformation, molecular surface hydrophobicity and electrostatic potential were analyzed and compared by using Insight II molecular modeling software. It was found that the conformation and molecular surface hydrophobicity of catalytic domains of TACE and MMPs were not obviously different, but the molecular surface electrostatic potential of catalytic domain of TACE and MMPs had obvious differences. The findings are helpful in the Rational Drug Design of TACE selective inhibitor. PMID- 17357476 TI - Screening of efficient siRNA target sites directed against gatekeeper genes for DNA repair. AB - To investigate the RNA interference (RNAi) effect induced by vector-derived small interfering RNA (siRNA) targeting the three gatekeeper genes (Rad52, Ku70, Ku80) and screen the more effective target sites from candidates for further research, by using siRNA design tools online, we selected 2 candidate sequences directed to every gatekeeper gene. According to the sequences, six vector-derived siRNAs (denoted psiRNA1-6) and one mocking psiRNA7 were constructed. Among them, psiRNA1 and psiRNA2 targeted Rad52, psiRNA3 and psiRNA4 to Ku70, psiRNA5 and psiRNA6 to Ku80. The mocking psiRNA7 was used as control. After sequence identification, the seven plasmids were transfected into HepG2 cell line. siRNA-induced silencing of gatekeeper genes was determined by using RT-PCR at RNA level and Western Blot at protein level. The results showed that the six plasmids specifically targeting the coding region of gatekeeper genes were successfully designed and constructed. To some extent, the six plasmids could reduce the expression of target gene. Comparatively, the plasmid-derived siRNA psiRNA1, psiRNA4 and psiRNA5 were more effective than their counterparts. The results suggest that the gene silencing efficiency of siRNA is different, depending on their targeted region, and siRNA may provide us with practical tools for further study on the three gatekeeper genes, i.e. Rad52, Ku70, Ku80. PMID- 17357477 TI - Inhibitory effect of oxymatrine on quartz-induced secretion of TNF-alpha by the pulmonary alveolar macrophages in the fibroblast proliferation. AB - To study the inhibitory effect of oxymatrine (OM) on quartz-induced secretion of TNF-alpha in the fibroblast proliferation, a given amount of quartz powder and OM of different concentrations were put into the media of pure culture containing macrophages. After 24 h of the culture, the TNF-alpha in the media was measured by double-antibody sandwich ELISA. The TNF-alpha (10 ng/mL) and OM of different concentrations were added into the media containing the fibroblasts of the 4th generations from neonate rats. The gamma values of cAMP and cGMP in fibroblasts were determined by the radioimmunoassay and the concentrations of cAMP and cGMP were calculated according to standard curve. The intracellular Ca2+ was determined by flow cytometry and cell proliferation was detected by MTT. Our results showed that at the concentrations between 200 microg/ mL-1600 microg/mL, OM inhibited the secretion of TNF-alpha by alveolar macrophages (AM) in a dose dependent manner. Especially, there were significant differences, to various degrees, in the inhibitory effect of OM between the concentration range of 800 microg/mL-1600 microg/mL and the concentration of 10 ng/mL TNF-alpha. When compared with 10 ng/mL TNF-alpha, OM of different concentrations could dose independently increased the level of intracellular cAMP and decreased the level of cGMP, thereby raising the ratio of cAMP/cGMP and lowering the concentrations of intracellular Ca2+. Moreover, OM of 800 microg/mL had the strongest inhibitory effect on cell proliferation and at this concentration, the cAMP/cGMP was highest and Ca2+ was at the lowest level. We are led to conclude that OM can antagonize the damaging effect of quartz on the membrane of AM and the effect of TNF-alpha promoting the proliferation of fibroblasts. It achieves its inhibitory effect on the promoting effect of TNF-alpha on fibroblast proliferation by elevating the cAMP level and decreasing the release of Ca2+. PMID- 17357478 TI - TNF-alpha up-regulates matrix metalloproteinase-9 expression and activity in alveolar macrophages from patients with chronic obstructive pulmonary disease. AB - To study the effects of tumor necrosis factor (TNF)-alpha on matrix metalloproteinase (MMP)-9 expression and activity in alveolar macrophages (AM) and to investigate the role of NF-kappaB in the induction, AM were collected from bronchoalveolar lavage fluid (BALF) of healthy subjects and patients with chronic obstructive pulmonary disease (COPD). MMP-9 expression and activity were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and zymography. NF-kappaB activity was detected by electrophoretic mobility shift assay (EMSA). MMP-9 expression and activity induced by TNF-alpha in AM from healthy subjects or patients with COPD were significantly increased in a dose-dependent manner (P<0.05). NF-kappaB activity induced by TNF-alpha was significantly increased in AM from patients with COPD, and pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC) significantly inhibited the activation of NF-kappaB induced by TNF-alpha (P<0.05). The presents study suggested that the expression and activity of MMP-9 from AM can be induced by TNF-alpha, and TNF-alpha/NF-kappaB signal pathway may play an important role in the induction. PMID- 17357479 TI - Different expressions of protein kinase C-alpha, beta I and beta II in glomeruli of diabetic nephropathy patients. AB - In current study, the expressions of protein kinase C (PKC)-alpha, beta I and beta II as well as their correlation to the expression of transforming growth factor-beta I (TGF-beta I) and vascular endothelial growth factor (VEGF) were investigated in glomeruli of normal renal tissues taken from human kidney tumors and kidney tissues from patients with diabetic nephropathy (DN). The accumulation of glomerular extracellular matrix (ECM) was determined by PAS staining, the expressions of PKC-a, PKC-beta I, PKC-beta II, TGF-beta I and VEGF were measured by semi-quantitative immunohistochemistry. Our results showed that in glomeruli of normal renal tissues, PKC-alpha and beta II had a strong expression whereas the expression of PKC-beta I was weak; in glomeruli of DN patients, the expressions of PKC-alpha, PKC-beta I, VEGF and TGF-beta I and the accumulation of ECM increased significantly, but the expression of PKC-beta II decreased markedly. Meanwhile, the expressions of PKC-alpha and beta I had a positive correlation to the expressions of VEGF and TGF-beta I respectively, whereas PKC beta II showed no correlation to VEGF and TGF-beta I. It is concluded that the expressions of PKC-alpha, beta I and beta II in glomeruli of normal subjects and DN patients are different. PKC-alpha seems to play a critical role in human DN by up-regulating VEGF expression, whereas PKC-beta I is relatively important for the up-regulation of TGF-beta I and the accumulation of ECM under diabetic conditions. PMID- 17357480 TI - Effects of impaired glucose metabolism on heart rate variability and blood pressure variability in essential hypertension patients. AB - To investigate the effects of impaired glucose metabolism (IGM) on cardiovascular autonomic nervous systems in essential hypertensive (EH) patients by comparing heart rate variability (HRV) and blood pressure variability (BPV) in EH patients with or without type 2 diabetes mellitus (T2DM). Simultaneous 24-h recordings of ambulatory ECG and blood pressure monitoring were performed in 36 male old patients with simple EH and 33 male old patients with EH combined with T2DM. HRV analysis included time domain parameters such as SDNN, SDANN, SDNNi, rMSSD and pNN50, and total spectral power (TP) of HRV, which mainly consists of VLF, LF and HF component along with LF/HF ratio, was also obtained. The value of ambulatory blood pressure was represented as the mean blood pressure (mean systolic/mSBP, diastolic/mDBP and pulse pressure/mPP) during different periods (24 h/24 h, day time/d and night time/n). Standard deviation (SD) as well as coefficient of variance (CV) of blood pressure during each above-mentioned period were obtained to reflect the long-term BPV. Our result showed that SDNN, SDNNi, SDANN, rMSSD, PNN50, TP and HF of HRV in cases of EH with T2DM were all significantly lower than those in simple EH subjects (P<0.05). No significant differences in VLF or LF was found between the two groups (P>0.05), while LF/HF ratio was significantly higher in EH with T2DM patients than in simple EH subjects (P<0.01). Moreover, dmSBP, 24 h-mPP and dmPP were all significantly higher in EH with T2DM patients than in simple EH subjects (P<0.05), while nmSBP, 24 h-mSBP, 24 h-mDBP, dmDBP, nmDBP or nmPP showed no significant difference between this two groups of patients (P>0.05). And dSBPSD, dSBPCV and 24 h-SBPSD were all significantly higher in EH with T2DM patients than in simple EH subjects (P<0.05), while the other BPV indexes showed no significant difference between this two groups (P>0.05). It is concluded that the cardiovascular autonomic nervous systems in EH patients was further impaired by T2DM, displaying lowering of HRV and enlargement of BPV, which in turn induced abnormal structural and functional changes of cardiovascular systems. Therefore, improving cardiovascular autonomic nervous systems might reduce the occurrence of cardiovascular complications in the EH patients with IGM. PMID- 17357481 TI - Role of coagulation factor VII in pathogenesis of ischemic heart disease. AB - To study the variation and significance of plasma coagulation factor VII (FVII) in different kinds of ischemia heart disease (IHD) and examine its relation with plasma lipid and gene polymorphism. FVIIa was determined with one stage clotting assay by using a recombinant soluble tissue factor (rsTF). FVIIc was measured with one stage clotting assay. FVIIag was quantified with an enzyme-linked immunosorbent assay (ELISA). Polymorphism was analyzed with PCR-urea polyacrylamide gel electrophoresis. Our results showed that FVIIa in stable angina (SA), unstable angina (UA), obsolete and acute myocardial infraction (OMI, AMI) patients was higher than those of normal group with the differences being significant within any two groups. FVIIag in UA, OMI and AMI was higher than those in SA and normal groups. There were positive correlations between FVIIa and serum triglycerides, FVIIa and FVIIc, FVIIc and FVIIag. FVII-323 0/10 bp polymorphism analysis was performed in 60 patients and 0/10 bp polymorphism was found in 5 cases. FVIIc and FVIIag were much lower in cases of 0/10 bp groups than those in cases of 0/0 bp groups. It is concluded that there was activation of extrinsic coagulation pathway in every kind of IHD to different extent. FVIIa was the risk factor in the development of IHD, and more sensitive in reflecting the severity of cardiovascular disease than FVIIc or FVIIag. FVIIa was higher in OMI, which may be one of the risk factors of re-infraction. Serum triglyceride may indirectly lead to the development of IHD by increasing the level of FVIIa. FVII-323 0/10 bp polymorphism was present in Chinese patients with IHD and it was correlated with the level of FVIIc, FVIIag in plasma. 10 bp allelomorphic gene was a protective factor against thrombogenesis. PMID- 17357482 TI - Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 chromosomal translocation in hematologic malignancies. AB - Multiplex reverse transcription-polymerase chain reaction (M-RT-PCR) has been proved to possess great clinical potential for simultaneous screening of 29 chromosomal translocations in acute leukemia. To evaluate the clinical value of M RT-PCR in hematologic malignancies, bone marrow samples from 90 patients with various hematologic malignancies, including 25 acute myelogenous leukemia (AML), 22 acute lymphoblastic leukemia (ALL), 27 chronic myelogenous leukemia (CML), 4 myeloproliferative diseases (MPD), 3 chronic lymphoblastic leukemia (CLL), 3 non Hodgkin's lymphoma (NHL), 3 myelodysplastic syndrome (MDS), 2 multiple myeloma (MM) and 1 malignant histiocytosis (MH) were subjected to both M-RT-PCR and chromosome karyotypic analysis. Some of cases were subjected to follow-up examination of M-RT-PCR during the period of clinical complete remission (CR) for detection of minimal residual leukemia. In our hand, 12 of 29 chromosomal translocation transcripts including TEL/PDGFR, DEK/CAN, MLL/AF6, AML1/ETO, MLL/AF9, BCR/ABL, MLL/MLL, PML/RARu, TLS/ERG, E2A/HLF, EVI1 and HOXI1 were detected in 57 cases (63.3 %) of the 90 samples, which were in consistency with the results of karyotypic analysis. Furthermore, M-RT-PCR had also shown good clinical relevance when used as an approach to detect minimal residual leukemia. We concluded that M-RT-PCR could be used as an efficient and fast diagnostic tool not only in the initial diagnosis of hematologic malignancies but also in subsequent monitor of minimal residual leukemia. PMID- 17357483 TI - The expression of molecular chaperone HSP90 and IL-6 in patients with systemic lupus erythematosus. AB - To explore the expression and clinical significance of molecular chaperone heat shock protein 90 (HSP90) in peripheral blood mononuclear cells (PBMC) and plasma level of interleukin-6 (IL-6) in patients with systemic lupus erythematosus (SLE), HSP90 was detected in PBMC by Western blot assay and the plasma level of IL-6 was measured by ELISA in 38 SLE patients and 20 normal controls. The correlation analysis was performed between the SLE disease activity index (SLE DAI) and the expression of HSP90 and IL-6. The results showed that there was increased expression of HSP90 in the SLE patients. The active SLE group exhibited higher HSP90 levels (0.82+/-0.10) than the inactive SLE group (0.54+/-0.09) (P<0.01). The expression of HSP90 in normal control group (0.37+/-0.11) showed significant statistical difference as compared to both the inactive and active SLE groups (P<0.01, P<0.01, respectively). The plasma level of IL-6 exhibited a significant increase in both the inactive and active SLE groups (28.99+/-1.74 pg/mL, 44.58+/-9.15 pg/mL, respectively) compared with normal control group (P<0.01, P<0.01, respectively). The expression of HSP90 and IL-6 in SLE patients showed significant positive correlation with SLEDAI scoring (r=0.80, P<0.01: r= 0.74, P<0.01, respectively). In addition, there was a positive correlation between the level of IL-6 and HSP90 in SLE patients (r=0.86, P<0.01). The increased expression of molecular chaperone HSP90 and IL-6 may play an important role in the pathogenesis of SLE by regulating autoimmunity. PMID- 17357484 TI - The protective effect of rosuvastatin on ischemic brain injury and its mechanism. AB - To study the protective effect of rosuvastatin on ischemic brain injury and its mechanism, focal cerebral ischemia/reperfusion was induced by occlusion of the middle cerebral artery (MCA) using the intra-luminal filament technique. The cerebral blood flow was monitored with laser-Doppler flowmetry (LDF). The slices of brain tissue were stained with cresyl-violet. The cerebral volume of infarction and edema were quantified with Image J software. The expressions of endothelial NO synthase (eNOS) and activated caspase-3 were detected with Western blot. The inducible NO synthase (iNOS) positive cells were immunohistochemically observed. The results demonstrated that rosuvastatin (20 mg/kg) could remarkably decrease infarct volume and cerebral edema after MCAO 90 min/reperfusion 24 h. Western blots showed that the expression of eNOS in cerebral cortex before and after ischemia was (100+/-43.3) %, (1668.9+/-112.2) % respectively (P<0.001), rosuvastatin significantly up-regulated the expression of eNOS in non-ischemic cortex (P<0.001), whereas in ischemic cortex of rosuvastatin group the expression of eNOS was (1678.8+/-121.3) %. There was no expression of activated caspase-3 in non-ischemic cortex, nonetheless the expression of activated caspase-3 increased after ischemia, and rosuvastatin significantly diminished it (P<0.01). Immunohistochemistry revealed no iNOS-positive cells in non-ischemic brain area, while in ischemic brain area the number of iNOS positive cells went up, and rosuvastatin could significantly reduced them. Consequently, the mechanisms of rosuvastatin's neural protection on ischemic brain injury are to enhance expression of eNOS, to inhibit expression of iNOS and activated caspase-3. PMID- 17357485 TI - Intrastriatal gene transfer of vascular endothelial growth factor rescues dopaminergic neurons in a rat Parkinson's disease model. AB - To examine the ability of intrastriatal gene transfer of vascular endothelial growth factor 165 mediated by adenoviral vector to rescue dopaminergic neurons in a rat model of Parkinson's disease (PD), we constructed recombinant replication deficient adenoviral vectors carrying the gene of VEGF165 (Ad-VEGF), and injected Ad-VEGF (or Ad-LacZ and PBS as controls) into the striatum of rats 7 days after the lesion by 6-hydroxydopamine. The rat rotational behavior analysis and tyrosine hydroxylase (TH) immunohistochemistry were performed to assess the change of dopaminergic neurons. Our results showed that the rats receiving Ad VEGF injection displayed a significant improvement in apomorphine-induced rotational behavior and a significant preservation of TH-positive neurons and fibers compared with control animals. It is concluded that intrastriatal gene transfer by Ad-VEGF may rescue the dopaminergic neurons from degeneration in a rat model of PD. PMID- 17357486 TI - Comparative study on cancer cell apoptosis between gastric and intestinal-type human gastric carcinoma. AB - Apoptosis of cancer cells between the gastric and intestinal-type human gastric carcinoma were compared in terms of the expression of oncogene MDM2 and CD68, the histological types, the infiltration depth, and lymph node metastasis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay was employed to stain apoptotic cells. Histochemical method(AB-PAS) was applied to stain mucus that is neutral or acidic in nature. Immunohistochemical method (SABC) was used to detect expression of MDM2 and CD6. The results showed that the mean apoptosis index (AI) of total 48 cases was 8.60+/-2.60. AI in the 30 intestinal type cases was significantly higher than that in the 18 gastric type cases (t=4.67, P<0.01). In the 30 intestinal type cases, the spontaneous apoptosis index of MDM2 negative cases was significantly higher than that of the positive cases (t=7.16, P<0.01). And in the 18 gastric type cases, the same result was found. (t=11.39, P<0.01). The MDM2 positive ratio in gastric type cases was higher than that in intestinal type cases (chi2=4.68, P<0.05). There is no significant difference in AI between cases of lymph node metastasis and non metastasis cases in intestinal type cases (t=0.26, P>0.05). But in the gastric type cases, a significant difference existed (t=5.87, P<0.01). A significant difference in lymph node metastasis ratio was found between the two gastric carcinoma types (chi2=4.48, P<0.05). The CD68 expression ratio in the 30 intestinal type cases was much lower than that in the 18 gastric type cases (t=4.29, P<0.01). AI of 25 MDM2-positive cases was much lower than that of the 23 MDM2-negative cases (t=7.80, P<0.01). CD68 positive ratio in the 25 MDM2-negative cases was much lower than that in the 23 negative cases. The difference was statistically significant (t=10.90, P<0.01). Except for few cells scattering within the cancer nest, most CD68 positive cells infiltrated in the interstitium around the cancer tissue. In the high-AI cases, CD68-positive cells increased. And the CD68-positive cells decreased in low-AI cases (r=0.96, P<0.01). Logistic regression analysis suggested that among the control variables, only AI was a statistically significant factor in the regression model (chi2=9.64, P<0.01). We concluded that (1) the spontaneous apoptosis index in gastric-type cases of gastric carcinoma was significantly lower than that in intestinal type cases; (2) AI in the two types was influenced by the expression of MDM2 and lymph node metastasis, but no visible connection was found between AI and the infiltration depth or histological types; (3) in the intestinal type cases, AI and the CD68 positive cells increased in MDM2-negative cases. PMID- 17357487 TI - Protective effect of curcumin on endotoxin-induced acute lung injury in rats. AB - To investigate the protective effect of curcumin on endotoxin-induced acute lung injury in rats, and explore the underlying mechanisms, 24 male Wistar rats were randomly divided into 4 experimental groups: sham-vehicle (S), sham-curcumin (C), lipopolysaccharide (LPS)-vehicle (L), and curcumin-lipopolysaccharide (C-L) groups. The wet/dry (W/D) weight ratio of the lung and bronchoalveolar lavage (BAL) fluid protein content were used as measures of lung injury. Neutrophil recruitment and activation were evaluated by BAL fluid cellularity and myeloperoxidase (MPO) activity in cell-free BAL and lung tissue. The levels of cytokine-induced neutrophil chemoattractant-I (CINC-1) in lung tissues were measured by ELISA. The histopathological changes of lung tissues were observed by using the HE staining. Our results showed that lung injury parameters, including the wet/dry weight ratio and protein content in BALF, were significantly higher in the L group than in the S group (P<0.01). In the L group, higher numbers of neutrophils and greater MPO activity in cell-free BAL and lung homogenates were observed when compared with the S group (P<0.01). There was a marked increase in CINC-1 levels in lung tissues in response to LPS challenge (P<0.01, L group vs S group). Curcumin pretreatment significantly attenuated LPS-induced changes in these indices. LPS caused extensive morphological lung damage, which was also lessened after curcumin pretreatment. All the above-mentioned parameters in the C group were not significantly different from those of the S group. It is concluded that curcumin pretreatment attenuates LPS-induced lung injury in rats. This beneficial effect of curcumin may involves, in part, inhibition of neutrophilic recruitment and activity, possibly through inhibition of lung CINC-1 expression. PMID- 17357488 TI - Relationship between PTEN and VEGF expression and clinicopathological characteristics in HCC. AB - To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homolog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC), and to analyze the relationship between their expressions and the tumor's invasion and their peri-carcinomatous tissues, the correlation of their expressions with the tumor's clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in peri-carcinomatous liver tissues, while the expressions of both VEGF and MVD were higher than that in peri-carcinomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively related to the progression of the pathological differentiation and invasion of tumor, whereas the expressions of VEGF and MVD were positively related. Moreover, there was a negative relationship between the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression probably induces abnormal hyperexpression of VEGF may play an important role in the invasion and metastasis of HCC. PMID- 17357489 TI - Effects of Danshen injection on the malignant obstructive jaundice in the SD rat model. AB - To observe the effects of Danshen on the growth of hepatocellular carcinoma in the SD rats, a model of malignant obstructive jaundice was established by inoculation of transplanted tumor into the hepatic portal with the walker-256 hepatocarcinoma line, which resulted in the obstruction by the infiltration and metastasis of hepatocellular carcinoma. SD rats were divided into 4 groups: the rats were treated by 0.9 % NS (n=24, control group), inosine+vitamin C (n=40, InV group), Danshen (n=40, DS group) and 5-FU (n=40, 5-FU group), respectively. The liver function, morphological changes and the expressions of PCNA, VEGF and ICAM 1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe (left-internal lobe) and lung tissues were observed after the treatment with the 4 agents. Our results showed that the protective effect of Danshen on liver function was significantly better than that of NS and 5-FU (P<0.01). No significant difference in protective effect was observed between DS group and InV group (P>0.05). Danshen also provided protective effect on the morphological damage of liver caused by obstructive jaundice. The rates of carcinoma-inhibition and metastasis inhibition were significantly higher than those of NS and inosine+vitamin C (P<0.01). No significant difference in this regard existed between DS group and 5-FU group (P>0.05). The expressions of PCNA,VEGF and ICAM-1 PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe (left-internal lobe) and lung tissues were lower than those in control group and InV group, with the differences being significant (P<0.01). No significant differences were found between DS group and 5-FU group in the expression levels of PCNA and VEGF (P>0.05) but ICAM-1 (P<0.05). It is concluded that Danshen injection not only has protective effects on liver injury caused by obstructive jaundice, but can inhibit the proliferation and growth of hepatocarcinoma, interfere with the vascularization of tumors, prevent recurrence and metastasis of hepatocarcinoma. PMID- 17357490 TI - Cardioprotective effects of diazoxide on myocardial ischemia/reperfusion injury in rats. AB - In order to study the cardioprotective effects of diazoxide on the myocardial ischemia/reperfusion injury of rats and mechanisms, the healthy SD rats were randomly divided into 2 groups: the rats in the experimental group were injected with diazoxide for preconditioning with the dosage of 12.5 mg/kg through the right femoral vein and those in the control group was only administered with the equal volume of media. After 10 min, a left thoracotomy was performed and the left anterior descending branch was occluded for 2 h. Two h later, the left anterior descending branch was reperfused for 2 h and then the heart was quickly excised to be used for measurement of MDA, SOD and the infarct size, in situ cell apoptosis detection and observation of the cell ultrastructure by electron microscopy. The results showed that as compared with the control group. MDA, the infarct size and cell apoptosis in the experimental group were greatly reduced (P<0.05). And the cell ultrastructure was obviously improved. But the activity of SOD had no change (P>0.05). It was concluded that diazoxide could protect the rats from myocardial ischemia/reperfusion injury, which might be contributed to the reduction of lipid peroxidation and cell apoptosis. PMID- 17357491 TI - Univariate risk factors for prolonged mechanical ventilation in patients undergoing prosthetic heart valves replacement surgery. AB - Data from 736 patients undergoing prosthetic heart valve replacement surgery and concomitant surgery (combined surgery) from January 1998 to January 2004 at Union Hospital were retrospectively reviewed. Univariate logistic regression analyses were conducted to identify risk factors For prolonged mechanical ventilation. The results showed that prolonged cardiopulmonary bypass duration, prolonged aortic cross clamp time and low ejection fraction less than 50 percent (50%) were found to be independent predictors for prolonged mechanical ventilation. Meanwhile age, weight, and preoperative hospital stay (days) were not found to be associated with prolonged mechanical ventilation. It was concluded that, for age and weight, this might be due to the lower number of old age patients (70 years and above) included in our study and genetic body structure of majority Chinese population that favor them to be in normal weight, respectively. PMID- 17357492 TI - Influence of transplantation of allogenic bone marrow mononuclear cells on the left ventricular remodeling of rat after acute myocardial infarction. AB - To probe into the influence of transplantation of allogenic bone marrow mononuclear cells (BM-MNCs) on the left ventricular remodeling of rat after acute myocardial infarction (AMI), 60 male Wistar rats were evenly divided into three groups at random: control group 1, control group 2 and transplantation group. In control group 1, chest was opened without ligation of coronary artery; in control group 2 and transplantation group, the left anterior descending branch of coronary artery was ligated to establish AMI model. Prepared culture medium and allogenic BM-MNCs suspension were respectively implanted the surrounding area of infarcted cardiac muscle via epicardium of control group 2 and transplantation group. Four weeks after the operation, the osteopontin gene (OPN mRNA, P<0.01), type I collagen (P<0.01) and angiotensin II (AngII, P<0.01) content in the left ventricular non-infarcted myocardium, and the Ang II density in blood plasma (P<0.05) of transplantation group and control group 2 were all significantly higher than that of control group 1. In the transplantation group, the myocardial OPN mRNA, type I collagen and Ang II content of non-infarcted zone in left ventricle, and the Ang II concentration in blood plasma were all significantly lower than those of control group 2 (P<0.05 for all). It is concluded that allogenic BM-MNCs transplantation may ease left ventricular remodeling after AMI by inhibiting the synthesis of type I collagen in the cardiac muscle and down regulating the expression of Ang II and OPN gene. PMID- 17357493 TI - Implication of EMT induced by TGF-beta1 in pancreatic cancer. AB - This study examined the implication of EMT induced by TGF-beta1 in pancreatic cancer invasion. TGF-beta1 expression was determined in 29 cases of human pancreatic carcinoma (PC) by immunohistochemistry and the results were compared with those of pathological examination. Moreover, the effects of TGF-beta1 on the phenotype and invasion of pancreatic cancer cell line Panc-1 were also investigated. TGF-beta1 was detected in 12 cases (41.4%) of PC. Significant correlation was found between the expression of TGF-beta1 and lymph node involvement (P=0.047) and the depth of invasion (P=0.035). TGF-beta1 obviously promoted EMT of Panc-1 cell lines and their invasion ability was substantially enhanced. TGF-beta1 may promote the malignancy of pancreatic cancer by triggering EMT. PMID- 17357494 TI - Effects of peptide nucleic acids against Ki-67 gene on the proliferation and apoptosis of human renal carcinoma cell line. AB - To investigate the effects of anti-sense peptide nucleic acids (PNAs) targeting Ki-67 gene on modulation of the proliferation and apoptosis of human renal carcinoma cell lines, human renal carcinoma cell line 786-0 cells were treated with anti-sense PNAs at different concentrations (1.0 micromol/L, 2.0 micromol/L, 10.0 micromol/L). The Ki-67 expression of 786-0 cells was detected by immunohistochemical technique and Western blot method respectively. The proliferation of 786-0 cells was studied by cell growth curves and 3H-thymidine incorporation. The apoptosis of 786-0 cells was detected by TUNEL assay. The control groups were treated with anti-sense oligonucleotide (ASODNs) targeting Ki 67 gene. Our results showed that the Ki-67 expression of 786-0 cells treated with anti-sense PNAs (16.9+/-0.7) was significantly inhibited as compared with that of the control groups (28.6+/-0.4) (P<0.01). The Ki-67 protein rate of 786-0 cells treated with anti-sense PNAs (42.1 +/-2.2) was significantly reduced when compared with that of the control groups (83.6+/- 1.4) (P<0.01). Proliferation of 786-0 cells treated with anti-sense PNAs (20.7+/- 1.5) was significantly inhibited as compared with that of the control groups (58.6+/- 1.4) (P<0.01). The apoptosis rate of 786-0 cells treated with anti-sense PNAs (28.7+/- 2.3) was significantly increased higher compared with that of the control groups (13.8 +/- 1.0) (P<0.01). From these finds we are led to conclude that anti-sense PNAs targeting Ki-67 gene have stronger effects on the inhibition of the proliferation and induction of apoptosis of human renal carcinoma cells than ASODNs targeting Ki-67 gene. The strategies using anti-sense PNAs targeting Ki-67 gene may be a promising approach for the treatment of renal cell carcinoma. PMID- 17357495 TI - Dynamic analysis of the expression of HSP70 during experimental tooth movement in rats. AB - In this study, the expression of HSP70 during experimental tooth movement was dynamically observed and the relationship between HSP70 and orthodontic periodontal tissue remodeling were observed. The orthodontic appliance was placed between the right maxillary first molar and maxillary central incisors of adult SD rats to establish a rat molar movement model. Immunohistochemistry was performed 1, 3, 5, 7 and 14 day(s) after orthodontic force application to observe the expression and localization of inducible HSP70. The expression of HSP70 was strongly positive in the early stage of the tooth movement, became gradually less positive, and was weakly positive in the restoration stage. There was difference in staining pattern between different parts of PDL during the same period. These results suggest that the expression of HSP70 and difference in staining pattern among different parts of PDL during orthodontic tooth movement in rats may be implicated in stress response and remodeling of periodontal tissue. PMID- 17357496 TI - Neurocyte apoptosis and expressions of caspase-3 and Fas after spinal cord injury and their implication in rats. AB - To study the expression of neurocyte apoptosis and the changes of caspase-3 and Fas after spinal cord injury (SCI) in rats, improved Allen's method was used to make model of acute SCI at the level of T9 and T10. The animals were divided into six groups: a control group and 5 injury groups. The segments of injured spinal cords were taken 6, 24, 48 h and 7, 15 days after injury for morphological studies, including HE staining, Hoechst33258 staining and TUNEL labeling. The expression of caspase-3 was detected by immunohistochemical staining and RT-PCR. TUNEL-positive cells began to appear in the compression region 6 h after the injury, mostly located in the gray matter. TUNEL-positive cells were found in both gray and white matter, reaching a peak at the 3rd day. They began to decrease at the 7th day, distributed mostly in the white matter. Fas increased at the 6th h and peaked at the 3rd day. Caspase-3 mRNA increased at the 6th h, peaking 48 h after the trauma, and decreased after 7 days. The protein expression of caspase-3, as revealed by immunohistochemical staining, was similar to TUNEL in time. It is concluded that apoptosis takes place after spinal cord injury, and caspase-3 mRNA and protein expressions were enhanced in the apoptosis. The expression of caspase-3 has a positive correlation with Fas expression. PMID- 17357497 TI - Effect of straight-leg-raising movement on epidural fibrosis in early stage after laminectomy in a rabbit model. AB - To determine the effect of straight-leg-raising (SLR) movement on epidural fibrosis after laminectomy, 40 adult New Zealand rabbits were selected as laminectomy models in the study. They were divided into 2 groups: a SLR group (group S) and a control group (group C) randomly, with each group having 20 animals. All rabbits were subjected to total laminectomy in the site of S1. Every 5 rabbits in each group selected randomly were killed at the 1st, 2nd, 4th, and 8th week after the surgery. Segments of spines from L7 to S2 were removed en bloc. After gross evaluation, specimens were sliced up. The slices were stained by HE and Masson's trichrome methods respectively for histological examination. Our results showed that formation process of scar in group S was retarded as compared with that of group C at the time of the 2nd-week, but there was no statistical difference between groups in the adhesion degree (P> or =0.05). At the 4th and 8th week, the epidural fibrosis of group S was more serious than that of group C. Since the 2nd-week, the area of scar in group S was larger than that of group C. The number of fibroblasts and inflammatory cells in group S were larger than those of group C at early stage. But in later stage, there was no statistical significance between the two groups. It is concluded that SLR movement after laminectomy may promote the formation of epidural fibrosis and retard the maturity of scar. SLR movement can also aggravate scar adhesion. PMID- 17357498 TI - The validity of osteoarthritis model induced by bilateral ovariectomy in guinea pig. AB - To evaluate the validity of osteoarthritis model induced by bilateral ovariectomy in guinea pig, 32-month-old female guinea pigs were randomly divided into two groups: a sham operation group (control group) and an ovariectomized group (OVX group). The animals were killed 6 or 12 weeks after the operation and the degeneration of the knees were assessed microscopically and histologically by scanning electron microscope (SEM), transmission electron microscope (TEM) and light microscope. The serum levels of estrogen and progesterone were detected by immune contest assay. The scoring of articular cartilage histopathology of tibial plateau was performed by histopathological examination. The blood serum levels of estrogen and progesterone were decreased significantly in the OVX group as compared with the control group 6 or 12 weeks after the operation. Joint cartilage degeneration as detected by SEM and TEM could be found at the 6th week, but severe degenerative lesions were observed at the 12th week in the OVX group as compared with the control group (P<0.01). The histopathological score of articular cartilage in tibial plateau in OVX group was higher than that of control group, which was coincident with the changes of estrogen and the ultrastructure (P<0.01). The findings suggested that bilateral ovariectomy in guinea pig can induce the severe osteoarthritis that is similar to the aging induced OA in human. Therefore, the model of the osteoarthritis by bilateral ovariectomy in guinea pig in this study is valid. PMID- 17357499 TI - Cytotoxicity study of a novel implant material modified by microarc oxidation. AB - This study examined the cytotoxicity of a new implant material modified by microarc oxidation technique. Cells on different surfaces of the implant were evaluated 2, 4 and 6 days after treatment. The results showed that cell attachment, cell morphology, and cell proliferation were influenced by the different surface treatments, and a significant increase in the osteoblast cell activity was observed on the porous MAO-Ti coating. Our results suggest that the porous MAO-Ti surface has a better biocompatibility and electrochemical performance than pure titanium surface. PMID- 17357500 TI - Immunomagnetic indirect positive sorting of precartilaginous stem cells from neonatal rat. AB - To investigate the technique of sorting high-purity precartilaginous stem cells from rat's perichondrium, neonatal rat's perichondrium cells suspensions were incubated with monoclone antibody of anti-fibroblast growth factor receptor-3 (anti-FGFR-3), and the labeled cells were separated from the suspension in the magnetic field by immuno-beads coated with the second antibody. Purity of the sorted neural stem cells was found to be 93.0%-99.0%, with living cells amounting to 80% -85 %. The magnetic cell sorting system could effectively separate precartilaginous stem cells from perichondrium cell suspensions. PMID- 17357501 TI - MR cholangiography and dynamic examination of duodenal fluid in the differential diagnosis between extrahepatic biliary atresia and infantile hepatitis syndrome. AB - In order to evaluate the value of magnetic resonance cholangiography (MRC) and dynamic examination of duodenal fluid in the differential diagnosis between extrahepatic biliary atresia (EHBA) and infantile hepatitis syndrome (IHS), 52 patients with infantile cholestatic jaundice were examined by MRC and duodenal fluid examination. Original interpretations were compared with clinical outcome. Calculated sensitivity of duodenal fluid examination in diagnosis of EHBA was 100%, and specificity was 91.1%. Sensitivity of MRC in the diagnosis of EHBA was 94.4% and specificity 88.24%. The sensitivity of MRC and examination of duodenal fluid combined in diagnosis of EHBA was 94.4% and specificity 97.06%. We are led to conclude that MRC and dynamic examination of duodenal fluid are useful in the differential diagnosis between IHS and EHBA and the combined use of the two techniques yield better results. PMID- 17357502 TI - Magnetic iron oxide nanoparticles mediated gene therapy for breast cancer--an in vitro study. AB - The aim of this study was to evaluate the feasibility and efficacy of using TRAIL gene to treat breast cancer mediated with a novel carrier - magnetic iron oxide nanoparticles (poly-MAG-1000) coated with PEI. The magnetic iron oxide nanoparticles were used as gene carrier to transfect TRAIL gene into MCF-7 cells. The polyMAG-1000 without TRAIL gene was transfected into the tumor cells as negative control. TRAIL gene transfection with liposome as carrier served as positive control. The apoptosis of cells was detected with TUNEL method. The apoptosis ratio of tumor cells was measured with flow cytometry (FCM). It was found that the apoptosis occurred in the tumor cells after transfection of TRAIL gene mediated by both polyMAG-1000 and liposome. The apoptosis ratio in the group with polyMAG-1000 as gene carrier was (25.11+/-2.85) %, whereas it was (5.06+/- 1.05) % in the control group with polyMAG-1000 (P<0.01). The apoptosis ratio was as low as (18.31+/-2.44) % in the group with liposome as gene carrier (P<0.05, as compared with the group with polyMAG-1000 as gene carrier). It is suggested that TRAIL gene may induce apoptosis in MCF-7 breast cancer cells. The magnetic iron oxide nanoparticles coated with PEI may be a potential gene carrier with high transfection efficacy for cancer gene therapy.. PMID- 17357503 TI - Down-regulation of beta-catenin nuclear localization by aspirin correlates with growth inhibition of Jurkat cell line. AB - In this study, we examined the effects of aspirin on the growth rates, subcellular distribution of beta-catenin protein, the expression of beta catenin/TCF signaling pathway target gene cyclin D1 mRNA, and cell cycle of Jurkat cell line (Human T-acute lymphoblastic leukemia). Our results showed that the treatment with aspirin inhibited the growth of Jurkat cell line. Jurkat cells treated with 3 mmol/L of aspirin could significantly decrease nuclear localization of beta-catenin, and at 5 mmol/L of aspirin, the nuclear localization of beta-catenin was undetectable. QRT-PCR showed that the target gene cyclin D1 mRNA expression was gradually decreased with the dosage of aspirin. Aspirin induced G0/G1 cell cycle arrest in Jurkat cells. We are led to conclude that aspirin acts through beta-catenin-independent mechanisms. The effects of aspirin include down-regulation of beta-catenin nuclear localization and G0/G1 cell cycle arrest, which might serve as a means of growth inhibition in aspirin-treated human Jurkat cell line. PMID- 17357504 TI - Reversal of adriamycin resistance in human mammary cancer cells by small interfering RNA of MDR1 and MDR3 genes. AB - The purpose of this paper is to investigate the reversal effect of small interfering RNA (siRNA) targeting MDR1 and MDR3 genes on the resistance of MCF 7/ADR cells to adriamycin. siRNA plasmid vector targeting MDR1 and MDR3 genes was transfected into MCF-7/ADR cells, and then was stained with Annexin-V FITC (fluorescein isothiocyanate conjugated) to detect the early stage cell apoptosis by flow cytometry (FCM). 50% inhibition concentration (IC50) of adriamycin for MCF-7/ADR cells was determined by MTT method. MDR1 and MDR3 mRNA was assessed by RT-PCR. Treatment of MCF-7/ADR cells with the two kinds of siRNAs resulted in a reversal of adriamycin resistance of MDR to different extents. 1) The apoptosis efficiency of MDR1 and MDR3 siRNA vector after transfection was (18.21+/-1.65) % and (9.07+/-2.16) % respectively (P<0.05), and there was significant differences in the apoptosis efficiency between p Suppressor Neo vector and the MDR1 siRNA or MDR3 siRNA vector (P<0.01); 2) The reversal effect of MDR1 siRNA is higher than that of MDR3 siRNA (P<0.05); 3) The expression of MDRI and MDR3 mRNA can be restrained by p Suppressor Neo MDR1 and MDR3 siRNA respectively, and the reduction in the mRNA level was in a time-dependent manner (P<0.01). MDR1 and MDR3 gene silencing can enhance intracellular adriamycin accumulation in MCF 7/ADR cells, improve sensitivity of MCF-7/ADR cells to adriamycin, and induce cell apoptosis. The reversal effect of adriamycin resistance by siRNA of MDR1 was more effective than that of MDR3. PMID- 17357505 TI - Correlation of RECK with matrix metalloproteinase-2 in regulation of trophoblast invasion of early pregnancy. AB - To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene and matrix metalloproteinase-2 (MMP-2) in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women (27 in the early pregnancy, 25 in the term pregnancy). Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syncytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group (P<0.05). RECK expression was significantly lower in cellular column (CC) with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy (P<0.05). The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35-0.14 and 2.68+/-0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time (P<0.01). The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46 +/- 0.05 and 0.10+/-0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2 may play an important role in the regulation of the trophoblast invasion in early pregnancy. PMID- 17357506 TI - Construction of three-dimensional in vitro culture model of ovarian carcinoma and the study of its multicellular drug resistance. AB - To explore the role and possible mechanism of apoptosis and caspase-3 activity in the development of multicellular drug resistance of ovary cancer. Ovarian cancer cell A2780 multicellular spheroids (MCS) were obtained from three-dimensional culture. Drug sensitivity of monolayer cells (MC) and MCS were respectively tested by MTT staining and cytometry. The apoptosis of MC and MCS were determined by the flow cytometry (FCM). The expression of bcl-2 and caspase-3 in A2780/MC and A2780/MCS were detected by using Western blot and caspase-3 assay kit. A2780/MC was compacted into mass after 2 days in three-dimensional cell culture model, and MCS had more than two layers of cells growing within 5 days. Compared with A2780/MC, A2780/MCS were more resistant to the anticancer drug, and the apoptosis rate was significantly lower than those of A2780/MC. The activity of caspase-3 in A2780/MCS was significantly lower than the A2780/MC. But the expression of bcl-2 in A2780/MCS was significantly higher than that in A2780/MC. It was suggested that the drug resistance of MCS might be associated with the overexpression of anti-apoptosis protein bcl-2 and the down-regulation of caspase 3 activity. PMID- 17357507 TI - Expression of RhoA in placenta of preeclampsia. AB - In order to detect the expression of RhoA in placenta from normal pregnancy and preeclampsia and evaluate the role of RhoA in preeclampsia, the expression of RhoA in placenta collected from 40 preeclampsia patients and 20 normotensive controls was determined by immunohistochemistry and RT-PCR. RhoA was found in syncytiotrophoblasts and cytotrophoblasts. The mean density of RhoA protein in placental tissues of mild and severe preeclampsia groups was significantly higher than that in normal pregnancy. The expression level of RhoA mRNA in mild and severe preeclampsia groups was significantly higher than that of normal pregnancy. Increased expression of RhoA in placental tissues might play an important role in the pathogenesis of preeclampsia. PMID- 17357508 TI - Expression of plasmacytoid dendritic cells, IRF-7, IFN-alpha mRNA in the lesions of psoriasis vulgaris. AB - To investigate the expression of plasmacytoid dendritic cells (pDCs), interferon regulatory factor-7 (IRF-7) and interferon alpha (IFN- alpha) mRNA in skin lesions of patients with psoriasis vulgaris, the expressions of plasmacytoid dendritic cells, IRF-7, IFN-alpha mRNA in the lesional skin of psoriasis vulgaris were detected by immunohistochemical technique (SP) and RT-PCR. Normal skin of healthy volunteers, serving as control, was also tested. The immunohistochemical study showed that the expression of pDCs in the psoriatic lesions was significantly higher than that in the normal controls. RT-PCR showed that the mRNA expression of IRF-7 was much higher than that in normal controls, but no difference in the expression of IFN-alpha mRNA was found between two groups. Our findings indicate that up-regulated expression of pDCs, IRF-7 mRNA might be involved in the pathogenesis of psoriasis. PMID- 17357509 TI - The expression of interleukin-23 (p19/p40) and interleukin-12 (p35/p40) in psoriasis skin. AB - In order to investigate the mRNA expression and function of interleukin-23 (p19/p40) and interleukin-12 (p35/p40) in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-23 (p19/p40) and IL-12 (p35/p40). The results showed that the expression of IL-23p19 mRNA and p40 (IL-12/IL-23) mRNA were higher in psoriatic lesion than those of non-lesional skin and normal skin. The levels of IL-23p19 mRNA and p40 (IL-12/IL-23) mRNA were higher in psoriatic non lesional skin than normal skin. However, no significant difference was found in the level of IL-12p35 mRNA among the psoriatic lesional skin, non-lesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL-12. PMID- 17357510 TI - Effects of sodium salicylate on the expression of HSP27 protein during oxidative stress in tissue-cultured human lens epithelial cells. AB - The effects of sodium salicylate on the expression of heat shock protein 27 (HSP27) during oxidative stress in tissue-cultured human lens epithelial cells were investigated. Cultured human lens epithelial cells (HLB-3) were divided into 3 groups: control group (group A), oxidation injury group (group B) and sodium salicylate group (group C). Apoptosis of human lens epithelial cells cultured in vitro was induced in the presence of 150 micromol/L H2O2. Cells viability and the expression of HSP27 were analyzed. Viability of the cells was measured by methyl thiazole tetrazolium (MTF) chromatometry. The expression of HSP27 in HLB-3 cells was detected by using immunohistochemistry and image analysis system. Sodium salicylate could induce the expression of HSP27, and the cells viability in group C was significantly higher than in group B (0.2667+/-0.01414 vs 0.2150+/-0.01080, P=0.012<0.05). The average gray value of HSP27 in group B was less than that in group C (P=0.000<0.05). The increased expression of HSP27 by sodium salicylate might play an important role in the protection of hydrogen peroxide-induced injury of human lens epithelial cells, suggesting that sodium salicylate could suppress, at least in part, the apoptosis of human lens epithelial cells. PMID- 17357511 TI - Investigation of peri-implant status and risk variables for implant failure in body of maxilla after oral tumor surgery. AB - The aim of this study was to assess the peri-implant parameters and evaluate the clinical status with the survival of dental implants in body of maxilla after treatments of oral tumor. A follow-up examination included 27 patients who underwent the ablative tumor and (or) reconstructive surgery during a 5-year period. The follow-up protocol included clinical examination, radiological evaluation, and an interview using a standardized questionnaire. The reasons related to implant failure were studied by comparing the amount of failure with the value of marginal bone resorption, probing pocket depth, and plaque index using statistical t-test. The relationship between smoking and implant failure was analyzed statistically by chi-square test. The results showed among the 112 implants observed after implant loading, 29 have failed with the failure rate being 22.14 %. There was no significant correlation between the peri-implant status and the implant failure (P>0.05), however, the association of smoking and implant failure was statistically tested (P<0.05). It was suggested that the association of peri-implant status and implant failure in the maxilla after tumor surgery can't be statistically tested, however smoking was still a mainly significant factor. PMID- 17357512 TI - A survey on the sexual and contraceptive behaviors in Chinese female college students. AB - To get information in the sexual and contraceptive behaviors in Chinese female college students, a randomized cluster sampling was conducted in colleges and universities in Wuhan Area, China, in terms of types of colleges, subjects (literature, sciences, medicines, art etc), and grades etc. A total number of 2450 questionnaires were distributed, with 2365 questionnaires returned being valid. The return rate of valid questionnaires was 96.6%. The questionnaire investigation was conducted on a multiple-choice and anonymous basis. Data were input into computer and SPSS12.0 software package was employed for statistical analysis. Among the female students, 1196 had the experiences of hug and kiss (50.57%) and 423 (17.89%) had sexual experiences (sexual intercourse). The first sexual intercourse took place at the age of 19.23+/-1.74 y. There were significant differences in the sexual experiences among the majors of different subjects, with the rate of sexual experiences in art majors (43.17%) and high grade students (34.31%) being the highest. The causes of the first sexual intercourse included sexual impulse, curiosity, intention to strengthen the relationship or to show loyalty to boyfriend and sometimes violence. While the motives of the sexual intercourse within the past one year before the investigation were to satisfy the sexual needs and to strengthen the relation with their boyfriends. With both first intercourse and sexual experiences within last one year, the partners of the sexual intercourse were mainly their boyfriends (95.7% and 97.3% respectively), but the partners also included acquaintances, "one night stand" partners and customers of sex trade. Some of them had multiple sexual partners, with the highest number of the sexual partners being 11. In the first sexual intercourse of the subjects, 44.0 % of them did not take any contraceptive measures; only 16.4% of them used condoms. In the sexual intercourse within the last one year, only 44.6% took contraceptive measures every time they had sexual intercourse. Among those who took contraceptive measures, 64.4% used condoms. Among those who had sexual intercourse, 101 persons got pregnant, with a rate of pregnancy being 4.3%, accounting for 23.9% of all who had sexual intercourse. Among those who got pregnant, 78 persons got pregnant once; the others became pregnant more than two times, the highest being 5 times. There were 122 persons who had inflammation of reproductive system, mostly vaginitis. Other conditions included venereal warts and herpes genitalis. It is concluded that the rate of sexual behaviors is high in female college students and there exist promiscuity, unexpected pregnancy and transmission of STD in the students. PMID- 17357513 TI - [The expression of tumor necrosis factor related apoptosis induce ligand in human laryngeal squamous cell carcinoma]. AB - OBJECTIVE: To study the expression of tumor necrosis factor related apoptosis induce ligand (TRAIL) receptors (DR4, DR5, DcR1, DcR2) in human laryngeal squamous cell carcinoma (LSCC). METHOD: The expression and distribution of DR4, DR5, DcR1, DcR2 were detected by immunohistochemical method in 68 patients of LSCC and 40 laryngeal normal tissues (LNT). RESULT: All of TRAIL receptors was observed in both tissues of LSCC and LNT. It was found that DR4, DR5 were overexpressed in the two tissues, indicating that there were no significant difference between the expressions of DR4 and DR5 in two tissues (P >0.05). DcR1 , DcR2 were over-expressed in LNT,were low expressed in LSCC (P <0. 05). Level of the TRAIL receptors DR5, DcR2 related with the degree of LSCC histological differentiation (P <0. 05). All receptors were not related with different clinical stage (P >0.05). CONCLUSION: TRAIL receptors expression is generally expressed in human LSCC and LNT. The expression level of TRAIL receptors is various, which may explain the anti-cancer effect of TRAIL. The TRAIL receptor DcR1, DcR2 may play an important role in the apoptosis regulation of LSCC. PMID- 17357514 TI - [Expression and clinical significance of matrix metalloproteinase-2 in laryngeal squamous cell carcinoma]. AB - OBJECTIVE: To investigate the relationship between the expression of matrix metalloproteinase-2 (MMP-2) and clinical significance of laryngeal squamous cell carcinomas (LSCC). METHOD: Expression of the MMP-2 was detected by immunohistochemical method in 63 cases of LSCC, 20 cases of adjacent safety margin (ASM) and 18 cases of vocal cord polyp (VCP). RESULT: The positive percentage of active MMP-2 expression were 66.7%, 33. 3% and 15. 0%, in LSCC,VCP and ASM respectively. Significant differences ( P <0. 05) were observed among the three group; there was a significant differences in the expression of MMP-2 among the different pathologic degree I , II , III; no significant difference in the expression of MMP-2 between lymphoid metastasis and no lymphoid metastasis ( P >0. 05); Age and clinical stage did not change the expressions of the MMP-2 expression ( P <0. 05). CONCLUSION: MMP-2 probably plays an important role in the carcinogenesis and progression of LSCC. But it may be an unnecessary factor in the metastases of LSCC. PMID- 17357515 TI - [The clinical significance of molecular findings in surgically resected margins of the primary tumor laryngeal carcinoma]. AB - OBJECTIVE: To study the relationship at molecular level between the resection range of laryngeal squamous cell carcinoma (LSCC) and prognosis. METHOD: Immunohistochemistry method was used to detected the expression of EGFR, p27,Bcl 2 and p53 in surgically resected margins of the 23 patients with LSCC. The relationship between the genes and tumour recurrence were observed by the follow up. RESULT: Seven margin tissues of tumors had detectable Bcl-2 expression; eleven margin tissues overexpressed p27; and three expressed p53 and EGFR. Four of the 23 patients have had tumor recurrence and their expression of p27, p53 and EGFR were negative; the expression of Bcl-2 was positive in two patients of the four recurrences patients. The rest were alive unrelated causes without clinical (good outcome). Expression of neither EGFR nor p53 was associated with recurrence. Only p27 was significantly associated with outcome and disease-free survival. CONCLUSION: These data indicate that assessing expression of multiple genes with immunohistochemistry in margin tissues is likely to be useful for surgically treated advanced laryngeal carcinoma. The expression of the p27 is more important. PMID- 17357516 TI - [Expression and clinical significance of survivin gene and PTEN gene in laryngeal squamous cell carcinomas]. AB - OBJECTIVE: To investigate the expression and clinical significance of anti apoptosis gene Survivin and tumor suppressor gene PTEN in laryngeal squamous cell carcinomas (LSCC) METHOD: The expression of Survivin and PTEN protein were detected by immunohistochemistry Envision method in 71 specimens of LSCC, and 10 specimens of vocal cord polyp as control. RESULT: No Survivin was detected in polyp of vocal cord. However, it was detected in 53 of 71 (74. 6%) specimens from the patients with LSCC. The Survivin expression was unrelated to the age and sex of patients or the size of tumors ( P >0.05) ,but related to the tumor site, clinical stage, histological grade, lymphatic metastasis and tumor prognosis ( P <0. 05). PTEN had the expression in all specimens of vocal cord polyp. However, it was detected in 33 of 71 (46. 5%) specimens of laryngeal carcinoma. The PTEN expression was unrelated to the clinical data including age, gender, tumor size and site ( P >0. 05), but related to the clinical stage, pathological grade, lymph node metastasis and prognosis ( P <0. 05). There was a negative correlation between Survivin expression and PTEN expression ( P <0. 05). CONCLUSION: The abnormal expression of Survivin and PTEN gene may be related to carcinogenesis, tumor progress and prognosis. The Survivin and PTEN gene may act as markers predicting biological behavior of LSCC. The coexpression of Survivin and PTEN gene have the synergism in carcinogenesis and tumor progress of LSCC. PMID- 17357517 TI - [Expression and clinical value of eukaryotic initiation factor 4E and matrix metalloproteinase-9 in supraglottic and hypopharyngeal carcinoma and metastasis lymph]. AB - OBJECTIVE: To study the expression of eukaryotic initiation factor4E (eIF4E)and matrix metalloproteinase-9 (MMP-9) in supraglottic, hypopharyngeal carcinoma, different distance surgical margins and lymphatic metastasis; to study the relationship of two molecular markers. METHOD: Expression of elF4E and MMP-9 in carcinoma and different margins were detected by HE-stained, routine pathological section, immunohistochemical SP method and image analysis. RESULT: (1) Immunohistochemical staining for MMP-9 was performed with a monoclonal anti-MMP-9 antibody. The positive expression rate was 68. 4 % . There was significant difference between lymph node metastasis and no lymph node metastasis, but there was no significant difference between T3 and T4 or T1 and T2 ( P >0. 05). There was no significant difference between MMP-9 and carcinoma position,pathology grade ( P> 0. 05). Positive expression rate of MMP-9 was decreased in tumour , 5 mm, 10 mm different distant margin of supraglottic and hypopharyngeal carcinoma as tissue progressed adjacent to carcinoma. (2) Staining positive rate of elF4E in supraglottic and hypopharyngeal carcinoma was 89%. There was significant association between eIF4E expression intensity and clinical stage, lymphatic metastasis. The positive expression rate of eIF4E was increased in sequence from 10 mm, 5 mm distant mucosa tissue to carcinoma nest in supraglottic and hypopharyngeal carcinoma. (3) Negative expression of MMP-9 and eIF4E was seen in the normal lymph nodes. MMP-9 positive expression rate was 28% in metastasis lymph nodes,elF4E was 42 %. (4) There was no significant correlation between elF4E and MMP-9 in margins according to spearman rank correlation test. CONCLUSION: eIF4E and MMP-9 expression was significantly higher in supraglottic and hypopharyngeal carcinoma than distant margin and normal mucosa tissue. elF4E positive rate was higher than MMP-9,expression sensitivity and reliability of elF4E in margins was higher than MMP-9. elF4E is a sensitive marker in growth, infiltration and metastasis of supraglottic and hypopharyngeal carcinoma. PMID- 17357518 TI - [Study on the expression of matrix metalloproteinase-12 and NM_002426 in squamous laryngeal carcinoma]. AB - OBJECTIVE: Matrix metalloproteinases (MMPs) are key factors which influence the grades and/or metastasis of stereo tumour. There are short of research of MMP-12 now. The experiment is done to investigate the expression of MMP-12 and NM_002426, and relationship between the two genes and the biologic behavior in squamous laryngeal carcinoma. METHOD: Thirty pairs of specimens, include supraglottic carcinoma tissue and normal mucosa, were chosen. Three gene arrays, based on different kinds of malignant, were made to study NM_ 002426 at first, then immunohistochemical method were used to observe the difference of MMP-12 between tumour and normal mucosa, metastasis group and no-metastasis group. RESULT: NM_002426 express high ratio in all 3 chips, and have the highest mark in both mid-level and high-level malignant tissue. The immunohistochemical results showed that MMP-12 had significant difference between tumour and normal mucosa, metastasis group and no-metastasis group. The MMP-12 expression was unrelated to different malignant degree. CONCLUSION: NM_ 002426 has significant hyperplasia in squamous laryngeal carcinoma, which caused high expression of MMP-12,and it makes a main contribution to the carcinogenesis and metastasis of laryngeal carcinoma. MMP-12 and its gene overexpress may be a auxiliary diagnosis method. PMID- 17357519 TI - [Expression of Endothelin-1 in laryngeal carcinoma]. AB - OBJECTIVE: To study the expression and clinical significance of Endothelin-1 in laryngeal carcinoma. METHOD: Immunohistochemical (SP) method was used to detect the expression of Endothelin-1 in 30 cases of laryngeal carcinoma,20 cases of laryngeal benign lesions and 10 cases of. The relationship between the expression of Endothelin-1 and the clinic stage was analysed by SPSS12. 0 software. RESULT. The positive expression of Endothelin-1 in all three type tissues. There is a significant difference between the laryngeal carcinoma and the laryngeal benign lesions, the laryngeal carcinoma and the normal laryngeal mucous membrane, the laryngeal benign lesions and the normal laryngeal mucous membrane( P <0. 05). The highest expression of Endothelin-1 is in laryngeal carcinoma tissue. In laryngeal carcinoma tissue, the advanced clinical stage, the more higher expression of endothelin-1. CONCLUSION: Positive expression of Endothelin-1 in laryngeal carcinoma tissue was highest in three tissue. It may be play an important role in carcinogenesis and progress of laryngeal carcinoma. PMID- 17357520 TI - [The clinical application of compound induced hypotension during functional endoscopic sinus surgery]. AB - OBJECTIVE: To assess the clinic efficacy of compound induced hypotension during functional endoscopic sinus surgery. METHOD: Sixty patients with chronic sinusitis and nasal polyps were divided into three groups: Sodium nitroprusside (SNP) group (A), diltiazem+SNP group (B), labetalol+SNP group (C). We started induced hypotension with beginning of functional endoscopic sinus surgery. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), cardiac index (CI) and ejection fraction (EF) were recorded during induced hypotension. Sugar and lactic acid in arterial and venous blood were also assayed. Then we calculate rate-pressure product (RPP), arteriovenous difference in blood glucose [D(v-a) BG], blood glucose extraction rate (BGER), arteriovenous difference in lactate [L(v-a)] and lactate produce rate (LPR). RESULT: The dose of SNP applied in group B and C are fewer than group A ( P <0. 05). The cardiovascular functions and body metabolism of the patients in group B and C were stable and the anesthetic effect was satisfactory. Few adverse reaction of the drug was found in present study. CONCLUSION: Induced hypotension with SNP compound of diltiazem or labetalol is an ideal way in clinical use and produce satisfied synergistic effect. PMID- 17357521 TI - [Osteogenic sarcoma in frontal sinus: one case with literature review]. AB - OBJECTIVE: To study the etiology, clinical manifestation, radiograph manifestation and treatment of osteogenic sarcoma in frontal sinus. METHOD: A case of osteogenic sarcoma of the frontal sinus is reported. Recurrent epistaxis and supra-orbital pain were presented as the chief complaint. CT scan revealed a mass in right frontal sinus and invasion to the inferior wall of the sinus. Treatment comprised lateral rhinotomy followed by radiotherapy and chemotherapy. RESULT: The patient was followed up 1 year and 9 month, and no recurrence or metastasis was found. CONCLUSION: The diagnosis of osteogenic sarcoma in frontal sinus should be made upon the following aspects: CT scan of the sinus, nasal endoscopic detection and biopsy. Radical surgery followed by radiotherapy and chemotherapy may be the main treatment. PMID- 17357522 TI - [Effects of keratinocyte growth factor on the expression and activity of extracellular signal-regulated kinase in Hep-2 cell line]. AB - OBJECTIVE: To observe effects of keratinocyte growth factor (KGF) on the proliferation of Hep-2 cell line; the activity and expression of extracellular signal-regulated kinase (ERK). METHOD: Cell line proliferation was measured by Flow cytometry and MTT assay; ERK activity was measured by ERKl/2 immuno precipitation kinase assay kit; and p ERK expression was assessed by Western blot. RESULT: KGF can improve the proliferation of Hep-2 cell line. The intracellular ERK activity and p-ERK expression were increased by different concentrations of KGF. CONCLUSION: KGF can stimulated proliferation of Hep-2 cell line with enhancing activity of ERK and expression of p-ERK. PMID- 17357523 TI - [Protective effects of minocycline against apoptosis of olfactory sensory neurons]. AB - OBJECTIVE: To investigate the protective effects of minocycline against apoptosis of olfactory sensory neurons induced by sinusitis. METHOD: Sixty adult SD rats were divided randomly into three groups: control group (group A), sinusitis group (group B) and intravenous injection of minocycline group (group C). The rats were sacrificed at 1,3,5 d and 7 d after surgery, and then the tissue sections of olfactory epithelium were stained and evaluated with hematoxylin and eosin (HE) and immunohistochemistry method. RESULT: The histopathological changes in maxillary sinus epithelium tissues observed with he staining microscopic examination in group B and C were worse than that in group A. Significant difference of the thickness of olfactory epithelium and Caspase-3 activity was demonstrated in group B and group C. CONCLUSION: The result demonstrated that minocycline could inhibit expression of Caspase-3 in rats with sinusitis. PMID- 17357524 TI - Judicial supervision of drug-abusing offenders. AB - In recent years,judges have been exercising steadily increasing influence over the disposition and management of drug abusers involved with the criminal justice system. This appears to have been motivated by a perception on the part of some judges that the courts are uniquely situated to bring about optimal outcomes for these individuals. In fact, the results of experimental and survey studies provide substantial support for this perspective, but only with regard to high risk drug offenders who have more severe antisocial predispositions or a history of not having responded to standard community-based drug abuse treatment services. This article reviews that research evidence and considers its implications for designing effective and cost-efficient policies and programs for drug-abusing criminal offenders. PMID- 17357525 TI - Prison-based treatment for drug-dependent women offenders: treatment versus no treatment. AB - This outcome study compared six- and 12-month return-to-custody data for 171 treatment participants and 145 nontreated general population inmates at the Central California Women's Facility (implementing a traditional TC program). Findings showed that there were no differences between the TC treatment group and the no treatment comparison group with regard to six- and 12-month return-to custody rates (six-month: 16% vs. 16% and 12-month: 36% vs. 27%). The only significant difference in six-month return-to-custody rates was found between treatment-only participants (21%) and the treatment plus aftercare participants (6%). Treatment participants who participated in community-based aftercare were significantly less likely to be returned to custody compared with those who did not participate in aftercare. Multivariate analysis was also used to control for the large difference in psychological impairment between the two groups and other background factors related to reincarceration, while assessing the effect of treatment group status on return-to-custody. Findings indicated that treatment/no treatment status was not significantly related to a six- or 12-month return-to custody. However, success on parole was associated with participation in community-based aftercare. The lack of a prison-based treatment effect could be an indication that drug-dependent women offenders need gender-responsive treatment that is designed specifically for their complex needs. PMID- 17357526 TI - California drug courts: outcomes, costs and promising practices: an overview of Phase II in a statewide study. AB - The rapid expansion of drug courts in California and the state's uncertain fiscal climate highlighted the need for definitive cost information on drug court programs. This study focused on creating a research design that can be utilized for statewide and national cost-assessment of drug courts by conducting in-depth case studies of the costs and benefits in nine adult drug courts in California. A Transactional Institutional Costs Analysis (TICA) approach was used, allowing researchers to calculate costs based on every individual's transactions within the drug court or the traditional criminal justice system. This methodology also allows the calculation of costs and benefits by agency (e.g., Public Defender's office, court, District Attorney). Results in the nine sites showed that the majority of agencies save money in processing an offender though drug court. Overall, for these nine study sites, participation in drug court saved the state over 9 million dollars in criminal justice and treatment costs due to lower recidivism in drug court participants. Based on the lessons learned in Phases I and II, Phase III of this study focuses on the creation of a web-based drug court cost self-evaluation tool (DC-CSET) that drug courts can use to determine their own costs and benefits. PMID- 17357527 TI - Evaluation of the Substance Abuse and Crime Prevention Act: client characteristics, treatment completion and re-offending three years after implementation. AB - Representing a major shift in criminal justice policy, Proposition 36 became law in November 2000 as the Substance Abuse and Crime Prevention Act (SACPA), permitting eligible offenders to receive probation with drug treatment instead of probation or incarceration. UCLA's Integrated Substance Abuse Programs was chosen by the California Department of Alcohol and Drug Programs to conduct an independent evaluation of SACPA. Analysis of the first three years of data provides information on the flow of offenders through SACPA, client and program characteristics, treatment completion rates, and effects on re-offending. Results show that most eligible offenders chose to participate in SACPA; almost two thirds of these went on to enter treatment. Compared to other treatment clients, SACPA treatment clients included fewer women, were predominately between 26 and 45 years old, were more likely to use methamphetamine, and had been using drugs a longer. Most SACPA clients were referred to outpatient drug-free treatment regardless of primary drug problem, and about one-third completed treatment. Re offending was lowest among SACPA offenders who completed treatment. Felony and misdemeanor drug arrests were higher among SACPA-era drug offenders than in a similar group of pre-SACPA drug offenders. Future reports will cover possible SACPA cost savings, additional clients outcomes, and overall lessons learned. PMID- 17357528 TI - California Substance Abuse Research Consortium, September 2005: update on recent methamphetamine trends in four California regions. AB - California Substance Abuse Research Consortium (SARC) meetings have become a mainstay in supporting the exchange of new alcohol and other drug information on research to policy and other initiatives throughout the state. A cornerstone of SARC is a discussion of regional substance abuse patterns and trends. This article provides readers with a brief overview of recently released methamphetamine statistics, as well as a more detailed review of the methamphetamine information presented during the substance abuse epidemiology portion of the September 2005 meeting, as presented for Kern County, Los Angeles County, San Diego County, the San Francisco Bay Area, and the state of California. PMID- 17357529 TI - The acceptability and feasibility of the Positive Reinforcement Opportunity Project, a community-based contingency management methamphetamine treatment program for gay and bisexual men in San Francisco. AB - The Positive Reinforcement Opportunity Project (PROP) was a pilot program developed to build on the efficacy of contingency management (CM) using positive reinforcement to address the treatment needs of gay and bisexual men currently using crystal methamphetamines (meth). It was hypothesized that a version of CM could be implemented in San Francisco that was less costly than traditional treatment methods and reached gay and other MSM using meth who also engaged in high-risk sexual activity. Of the 178 men who participated in PROPfrom December 2003 to December 2005, many self-reported behaviors for acquiring and spreading sexually transmitted diseases including HIV infection. During the initial intake, 73% reported high-risk sexual behavior in the prior three months, with 60% reporting anal receptive and/or insertive sex without condoms. This report describes the implementation of PROP and suggest both its limitations and potential strengths. Initial findings suggest that PROP was a useful and low cost substance use treatment option that resulted in a 35% 90-day completion rate, which is similar to graduation rates from traditional, more costly treatment options. Further evaluation of the limited data from three- and six-month follow up of those who completed PROP is currently ongoing. PMID- 17357530 TI - Craving and control: methamphetamine users' narratives. AB - In this article the authors explore the experience of craving of methamphetamine users and seek to illuminate how differences in craving contribute to use patterns. Using in-depth interviewing, data were collected from 82 active methamphetamine users in the metropolitan Atlanta area. The constant comparison method common in grounded theory guided the data analysis. Narrative responses corresponded with three types of craving described in the literature: cue-, drug- and withdrawal-induced. However, the narratives also problematize this typological view as well as the characterization of craving as invariably leading to drug use. Types of craving cues were sometimes inseparable, and users indicated that the different types of craving could occur in the same situation. Further, many users described being able to overcome craving through personalized methods of control. This study complements the largely quantitative work on craving and highlights the importance of improving drug abuse treatment and harm reduction programs. PMID- 17357531 TI - Methamphetamine use and adverse consequences in the rural southern United States: an ethnographic overview. AB - Research on methamphetamine use and related issues often uses data from in treatment and post-treatment populations in urban areas. Rural ethnographic studies are less common, particularly self-assessments by active methamphetamine users that explore use patterns and their adverse consequences. Such work is especially rare in the rural South, where illicit methamphetamine manufacture and use have recently been increasing. This article presents an ethnographic overview of methamphetamine use in rural Kentucky and Arkansas based on qualitative interviews conducted with 34 active, not-in-treatment, primary methamphetamine users. Methamphetamine supply, distribution, and prevalence of methamphetamine use are described. Pathways and motivations for methamphetamine use and use patterns are outlined as well. A discussion of the adverse consequences and potential risks of methamphetamine use follows. The findings indicate that informed drug treatment outreach and reduction of potential adverse consequences among methamphetamine users in rural areas are important issues for public health and for interventions. PMID- 17357532 TI - Perceived behavior of others and AIDS risk behavior among heterosexually identified methamphetamine users. AB - This study used cross-sectional data to examine perceived risk behavior of social network members as a correlate of AIDS risk behavior in a sample of 230 heterosexually-identified, methamphetamine (meth) users. The highest ratings of risk behavior within participants' social networks were associated with meth use and non-use of condoms. Friends received the highest ratings in terms of overall perceived involvement in drug and sexual risk behaviors. In a multivariate analysis, perceived risk behavior of others, social norms, and attitudes toward AIDS preventive behaviors were significantly associated with intentions to always use condoms. Strategies for addressing negative social influences in the context of sexual risk reduction interventions are described. PMID- 17357533 TI - Two-year outcomes of treatment for methamphetamine use. AB - While evaluation research supports the general effectiveness of substance abuse treatment, there is not a comprehensive literature on treatment effectiveness for methamphetamine (MA) use. The authors consider three outcome measures--MA use, criminal activity, and employment--compared across three periods: 24-months pretreatment, during treatment, and 24-months post-treatment. Data are from an intensive natural history interview conducted two to three years after treatment for 349 randomly selected admissions to treatment for MA abuse in a large publicly-funded county treatment system. Through this naturalistic design, data provide a system-wide perspective on effectiveness of treatment as usual. Results showed reduction in MA use and crime during and following treatment and increased employment following treatment over pretreatment levels. Regression analyses showed higher levels of education and more time in treatment related to more positive post-treatment outcomes for all three measures. Lower percentage of post treatment months with MA use also was related to more pretreatment MA-related problems, lower pretreatment MA use, and residential (compared to outpatient) treatment modality. Lower post-treatment criminal activity was also related to gender (being female), lower pretreatment criminal activity, and residential modality. Higher percentage of post-treatment months with employment also was related to gender (being male), ethnicity (not African-American), and higher pretreatment employment. PMID- 17357534 TI - Effect of nortriptyline on intracellular Ca2+ handling and viability in canine renal tubular cells. AB - In Madin-Darby canine kidney (MDCK) cells, the effect of nortriptyline, an antidepressant, on intracellular Ca2+ concentration ([Ca2+]i) was measured by using fura-2. Nortriptyline (> 10 microM) caused a rapid increase of [Ca2+]i in a concentration-dependent manner (EC50 = 75 microM). Nortriptyline-induced [Ca2+]i increase was prevented by 40% by removal of extracellular Ca2+ but was not altered by voltage-gated Ca2+ channel blockers. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic [Ca2+]i, increase, after which the increasing effect of nortriptyline on [Ca2+], was abolished; also, pretreatment with nortriptyline reduced a large portion of thapsigargin-induced [Ca2+]i increase. U73122, an inhibitor of phospholipase C, abolished ATP (but not nortriptyline)-induced [Ca2+]i increase. Overnight incubation with 10 microM nortriptyline decreased cell viability by 16%, and 50 microM nortriptyline killed all cells. Prechelation of cytosolic Ca2+ with BAPTA did not alter nortriptyline-induced cell death. These findings suggest that nortriptyline rapidly increased [Ca2+]i in renal tubular cells by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release, and was cytotoxic at higher concentrations in a Ca(2+)-dissociated manner. PMID- 17357535 TI - The antidepressant mirtazapine-induced cytosolic Ca2+ elevation and cytotoxicity in human osteosarcoma cells. AB - The effect of the antidepressant mirtazapine on cytosolic free Ca2+ concentration ([Ca2+]i) and viability has not been explored in any cell type. This study examined whether mirtazapine alters Ca2+ levels and causes cell death in osteoblast-like cells using MG63 human osteosarcoma cells as a model. [Ca2+]i and cell viability were measured using the fluorescent dyes fura-2 and WST-1, respectively. Mirtazapine at concentrations above 250 microM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 60% by removing extracellular Ca2+. The mirtazapine-induced Ca2+ influx was sensitive to blockade of nifedipine and verapamil. In Ca(2+)-free medium, after pretreatment with 1.5 mM mirtazapine, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 2 microM CCCP (a mitochondrial uncoupler), and 1 microM ionomycin failed to release more stored Ca2+; conversely, pretreatment with thapsigargin, CCCP and ionomycin abolished mirtazapine-induced Ca2+ release. Inhibition of phospholipase C with 2 microM U73122 did not change mirtazapine-induced [Ca2+]i, increase. Seal of Ca2+ movement across the plasma membrane with 50 microM extracellular La3+ enhanced 1 microM thapsigargin-induced [Ca2+]i increase, suggesting that Ca2+ efflux played a role in lowering thapsigargin-induced [Ca2+]i increase; however, the same La3+ treatment did not alter mirtazapine induced [Ca2+]i increase. At concentrations of 500 microM and 1000 microM, mirtazapine killed 30% and 60% cells, respectively. The cytotoxicity was not reversed by chelating cytosolic Ca2+ with BAPTA. Collectively, in MG63 cells, mirtazapine induced a [Ca2+]i increase by causing Ca2+ release from stores and Ca2+ influx from extracellular space. Furthermore, mirtazapine caused cytotoxicity at higher concentrations in a Ca(2+)-dissociated manner. PMID- 17357537 TI - Increased nitric oxide production accompanies blunted hypoxic pulmonary vasoconstriction in hyperoxic rat lung. AB - Hyperoxia may affect lung physiology in different ways. We investigated the effect of hyperoxia on the protein expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), nitric oxide (NO) production, and hypoxic pulmonary vasoconstriction (HPV) in rat lung. Twenty-four male rats were divided into hyperoxic and normoxic groups. Hyperoxic rats were placed in > 90% F1O2 for 60 h prior to experiments. After baseline in vitro analysis, the rats underwent isolated, perfused lung experiments. Two consecutive hypoxic challenges (10 min each) were administered with the administration of a non-specific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME), in between. We measured intravascular NO production, pulmonary arterial pressure, and protein expression of eNOS and iNOS by immunohistochemistry. We found that hyperoxia rats exhibited increased baseline NO production (P < 0.001) and blunted HPV response (P < 0.001) during hypoxic challenges compared to normoxia rats. We also detected a temporal association between the attenuation in HPV and increased NO production level with a negative pre-L-NAME correlation between HPV and NO (R = 0.52, P < 0.05). After L-NAME administration, a second hypoxic challenge restored the HPV response in the hyperoxic group. There were increased protein expression of eNOS (12.6 +/- 3.1-fold, n = 3) (X200) and iNOS (8.1 +/- 2.6-fold, n = 3) (X200) in the hyperoxia group. We conclude that hyperoxia increases the protein expression of eNOS and iNOS with a subsequent increased release of endogenous NO, which attenuates the HPV response. PMID- 17357536 TI - Tissue microarray-determined expression profiles of cyclooxygenase-2 in colorectal adenocarcinoma: association with clinicopathological parameters. AB - Accumulated evidence reveals that increased cyclooxygenase-2 (COX-2) is involved in the development of colorectal cancer. Our purpose was to quantitate COX-2 expression in colorectal cancers using tissue microarray analysis and look for an association with clinicopathological stage. Immunohistochemical analysis of COX-2 was performed in tissue microarray slides containing 90 specimens including 32 well-differentiated, 35 moderately differentiated, and 23 poorly differentiated colorectal adenocarcinomas. All colorectal adenocarcinomas showed significant immunohistochemical expression of COX-2 when compared to normal colon epithelia. However, there was no significant difference in immunostaining scores between poorly, moderately, and well-differentiated tumors (195 +/- 28, 214 +/- 26 and 200 +/- 24, respectively). The COX-2 immunostaining score correlated significantly with T stage (P < 0.05) but not with N or M stage. The positive expression rates of CK20 were 97% for well-differentiated, 94% for moderately differentiated, and 65% for poorly differentiated colorectal adenocarcinomas, suggesting that CK20 may not be an effective discriminator between poorly differentiated colorectal adenocarcinoma and metastatic adenocarcinoma. PMID- 17357538 TI - Vasopressin produces inhibition on phrenic nerve activity and apnea through V(1A) receptors in the area postrema in rats. AB - The area postrema (AP) is the most caudal circumventricular organ in the central nervous system and contains arginine vasopressin (AVP) receptors. To investigate that AVP receptors in the AP might participate in the modulation of respiration, the adult rat was anesthetized with urethane (1.2 g/kg, i.p.), paralyzed, ventilated artificially, and maintained at normocapnia in hyperoxia. The phrenic nerve was separated at C4 level. Phrenic burst was amplified, filtered, integrated, and then stored in the hard disc via the PowerLab system. Three doses of AVP and an AVP V(1A) receptor antagonist, [beta-mercapto-beta,beta cyclopentamethylenepropionyl1,-O-Me-Tyr2,Arg8]-vasopressin, were microinjected into the AP through a pair of microelectrodes. The moderate and high doses of AVP reduced the PNA to 72% and 45% of the control (P < 0.05), extended the mean TE from 1.4 s before AVP to 4.0 s and 7.6 s, (P < 0.05), and decrease in BP by 26 and 37 mmHg (P < 0.05), respectively. These significant reductions in PNA and BP and elongation of TE were totally abolished by the pre-treatment of the AVP V(1A) receptor antagonist and by application of lidocaine or CoCl2 at the nucleus tractus solitarius (NTS). Moreover, pulmonary inhibition caused by AVP was significantly attenuated by hypercapnia. These results strongly suggest that AVP V(1A) receptors in the AP may participate in the modulation of cardiopulmonary functions through the activation of V(1A) receptors and the pathway connected to the NTS. They may also indicate that a putative vasopressinergic pathway has a projection to the AP to alter the excitability of neurons having AVP V(1A) receptors and results in an inhibition of cardiopulmonary functions via the connection between the AP and NTS. PMID- 17357539 TI - Inhibition of inducible nitric oxide synthase in murine visceral larva migrans: effects on lung and liver damage. AB - The roles of nitric oxide production and oxidative process were studied in mice infected with Toxocara canis and treated with aminoguanidine which is a specific inhibitor of inducible nitric oxide synthase (iNOS). Relations of nitric oxide synthase inhibition and tissue pathology were assessed by biochemical, histological and immunohistochemical methods. In experiments, Balb/c albino mice were inoculated with T. canis eggs either with or without aminoguanidine treatment or alone, at 24th, 48th hours and on 7th days. LPx and SOD values in liver tissue and plasma were measured. Liver and lung tissues were evaluated for the pathological lesions. The expression of eNOS and iNOS in both tissues were studied with immunohistochemistry in the same intervals. We observed significant differences between T. canis infected and aminoguanidine treated animals. Larval toxocarosis led to oxidative stress elevation in plasma. Microscopic examination of the liver histological sections revealed pathological lesions in the hepatic parenchyma in infected mice. In the mice received T. canis eggs plus aminoguanidine, the sinusoidal areas were enlarged. Histological lesions were more severe at 48 hours after infection. Numbers of eNOS and iNOS expressing epithelial cells were increased in the T. canis infected mice. The activities of eNOS and iNOS were also observed in the body of the larvae which have migrated to lung and liver. As a result, we have demonstrated that in vivo production of eNO and iNO during T. canis infection cause direct host damages and it is strongly related to the oxidative stress. We propose that larval NO can also be effective in larval migration, but it needs further investigation on distribution of NO in larvae. PMID- 17357540 TI - Bone metabolism in ovariectomized rats with induced hyperthyroidism: the effect of estrogen replacement. AB - We aimed to investigate whether or not the estrogen is playing any role in the effect of thyroid hormones on bone metabolism. The rats were divided into five groups. In the first group L-thyroxine-induced hyperthyroid rats were ovariectomized (OVX) while the OVX rats were administered L-thyroxine in the second group. 17beta-Estradiol (E2) was replaced in OVX rats in Group III. L thyroxine and E2 were simultaneously administered to OVX rats in Group IV. The fifth group received sham operation. Blood samples taken from the tail vein of rats were analyzed for plasma T3, T4, TSH and serum interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)alpha, calcium (Ca), phosphorous (P), parathyroid [corrected] hormone (PTH), alkaline phosphatase (t-ALP), bone-specific alkaline phosphatase (b-ALP) and E2. The levels of cytokines, t-ALP and b-ALP increased but PTH decreased, while there was no change in Ca and P levels in L-thyroxine administrated rats. However, the levels of cytokines, Ca, P, PTH, t-ALP and b-ALP did not change in L-thyroxine-administered OVX rats. In OVX rats, the cytokines, t-ALP and b-ALP increased while Ca, P remained the same, but PTH decreased. L thyroxine administration to OVX rats did not change the cytokines, Ca, P, PTH, t ALP and b-ALP levels. The replacement of E2 in OVX rats decreased the cytokines, t-ALP and b-ALP values, increased PTH levels while there was no change in Ca and P. L-thyroxine and E2 administration to OVX rats increased the cytokines, t-ALP and b-ALP levels and decreased PTH, but Ca and P remained the same. In sham operated rats, there was no change in all parameters compared to initial values. This study suggests that estrogen may play a role in the effects of thyroid hormones on bone metabolism. PMID- 17357542 TI - Housing as a socio-economic determinant of health: findings of a national needs, gaps and opportunities assessment. AB - BACKGROUND: In 2002-2003, a Needs, Gaps and Opportunities Assessment (NGOA) was conducted to investigate relationships between socio-economic dimensions of housing and health. Recent reviews of the literature point to a dearth of research on the socio-economic dimensions of housing and health, despite its potential for promoting health. METHODS: The NGOA sought to identify research needs and gaps, and future opportunities for research in housing, socio-economic status and health. The methods used included a literature scan, a scan of research capacity, eight regional stakeholder workshops across Canada, and an open-ended e-mail survey of stakeholders. In this paper, we report the findings of the stakeholder consultations. FINDINGS: The main finding of the NGOA was that there is a significant dearth of research on housing as a socio-economic determinant of health but enormous potential for conducting high-impact, longitudinal and quasi-experimental research in the area. Of particular interest to stakeholder participants in the NGOA were the economic aspects of housing and health; the impact of housing on health for vulnerable subgroups (e.g., Aboriginal peoples, immigrants, children, seniors); the role of socio economically and ethnically mixed communities; and the interaction between socio economic aspects of housing and biophysical hazards in the home. CONCLUSION: The NGOA demonstrated that there is a substantial audience eager for knowledge on housing as a socio-economic determinant of health and that such knowledge could make an immediate impact on policy decision-making and program operation. Although knowledge gaps are substantial, the NGOA clearly identifies opportunities for high-impact, longitudinal and quasi-experimental research. Recently signed federal-provincial funding agreements for housing make the findings of the NGOA timely. Moreover, the NGOA results demonstrate how research on housing as a socio-economic determinant of health could be a strategy for improving our understanding of the effects of social environments on health and for reducing health disparities. PMID- 17357541 TI - Social assistance, lone parents and health: what do we know, where do we go? AB - BACKGROUND: A mounting body of evidence indicates that lone mothers and their children are at higher risk of a variety of health problems. The dynamics of the relationship between social assistance, poverty and health are not well understood, and the study of this population presents substantial challenges. The purpose of this paper is to present an analysis of the state of research on lone parents, social assistance and health in an effort to make recommendations that will move the research forward. METHODS: Reviews of the relevant literature and social policies were conducted to identify (1) trends in social assistance policy and the extent of interprovincial variation in policy, and (2) research gaps. A series of interviews were conducted with key informants in government, non governmental organizations and academia to gather information regarding research obstacles, opportunities and priorities. Finally, a consensus-building workshop was held to form research recommendations. RESULTS: A substantial degree of variation exists among provinces and territories with regard to social assistance policies. The nature of the variation, however, is complex and does not fall into tightly defined categories. This variation creates the possibility for "natural experiments" to examine the health implications of policies and practices. The pace of policy change, however, creates problems with respect to evaluation of specific policy initiatives. Interviewees and workshop participants recognized substantial impediments to research in this area, particularly regarding the availability of appropriate data. CONCLUSION: A research agenda, data development and dissemination activities were proposed to increase the research activity; these would be based upon multi-disciplinary, multi-sectoral collaborations using multiple methodologies. The creation of a multi-disciplinary, multi-sectoral national consortium in social assistance and health, reflecting the appropriate mix of urban, rural, anglophone, francophone and First Nations communities, is proposed. PMID- 17357543 TI - Income and health in Canada: research gaps and future opportunities. AB - BACKGROUND: The goal of this research project was to identify and suggest means of filling the gaps/needs in Canadian research activity and public policy action on the income and health relationship. METHODS: The research consisted of an environmental scan and analysis of 321 empirical research pieces from Canada (n = 241), the United Kingdom (n = 40) and Finland (n = 40) followed by a systematic gaps/needs analysis of these studies by members of three advisory committees, consisting of researchers and policy advocates. These data were complemented by key informant interviews with researchers from Canada, the UK and Finland. The gaps/needs were then reviewed and assigned priority rankings by members of the three advisory committees. FINDINGS: Numerous gaps/needs in Canadian research on income and health were apparent. They fell into five main areas: (a) training and capacity building in addressing income as a health determinant; (b) developing adequate data and measures; (c) researching specific substantive health issues; (d) researching specific public policy areas; and (e) developing an understanding of the pathways and mechanisms mediating the income and health relationship. Members of the advisory committees achieved a high level of agreement concerning these gaps/needs and means of reducing them. CONCLUSIONS: The Canadian Institutes of Health Research (CIHR) and the Institute of Population Health should target specific research initiatives to help fill the identified gaps in knowledge. They should also work together with public policy institutes to synthesize findings concerning income, its distribution, and health, and help distribute these findings to the public in general and policy-makers in particular. PMID- 17357544 TI - Needs, gaps and opportunities for infectious disease research in British Columbia: a perspective from population and public health. AB - BACKGROUND: A review of infectious disease research activity and capacity was performed in British Columbia and linked to a process for identifying needs, gaps and opportunities from a public health perspective. METHODS: The study was organized in three phases: an environmental scan to describe current research activity in BC; a consultation to identify needs, gaps and opportunities with those conducting research (key informants) and the end users of research results (stakeholders); and a prioritization of the research needs emerging from the consultation. RESULTS: Analysis and synthesis of the consultation data resulted in the identification of nine research themes, which were prioritized in the following order: efficacy and cost-benefit, disease patterns, emerging infectious disease, immunology and vaccines, disease-specific research, health promotion and communications, safe food and water, knowledge translation research and genomics. Six capacity-building themes were also identified: attraction and retention, education and training, collaboration and networks, funding, dissemination of findings, and public health input, surveillance, informatics and databases. INTERPRETATION: The findings were helpful in developing a multi-disciplinary, multi-level infectious disease research agenda linking researchers in universities, hospitals and public health institutions with practitioners and policy-makers in British Columbia's public health system. The approach is both feasible and important to undertake at the national level. PMID- 17357545 TI - [Lignan: an important natural estrogen from plants]. AB - Lignan is an important phytoestrogen with weakly estrogenic and anti-estrogenic properties, and possesses diverse bioactivities, including antioxidation, antitumor and antivirus etc. In particular, it may prevent hormone-dependent diseases, such as breast cancer, prostate cancer and benign prostatic hyperplasia. However, many important scientific problems have not been constrained, whether do the metabolites of lignans from foods have their potential genic toxicity? What are the anticancer mechanisms of lignans? What is the dosage of lignans to achieve the desired biological effect? In this paper, the references on lignans have systematically been reviewed in the following aspects: classification, distribution, metabolism, pharmacological activities and analytical methods, and a prospective of future studies on lignans is also elucidated. PMID- 17357546 TI - [Study on content variation of triptolide in medicinal material of Tripterygium]. AB - OBJECTIVE: To study the content variation of triptolide in medicinal material of Tripterygium and provide theoretical basis for the hereditary improvement, the gathering and process, the quality evaluation and the provenance division in medicinal material of Tripterygium. METHOD: HPLC method was used to determine the content of triptolide. RESULT: The relations between triptolide and germplasm, growth year, gathering season were found out basically. CONCLUSION: The triptolide contents in xylem are affected by hereditary factors remarkably. While the triptolide contents in phloem are not affected obviously. The accumulation of triptolide needs the certain growth years. However when growth is beyond certain years, the triptolide content decreases with the disintegration of secondary metabolism in xylem. The triptolide in xylem is highest in winter and decreasing in growing season. The triptolide in phloem is less affected by the season. PMID- 17357547 TI - [Studies on impact of temperature and weight in Whitmania pigra bred]. AB - OBJECTIVE: To determine the best spawning temperature and weight of Whitmania pigra and the hatching temperature of its eggs. METHOD: Observe the state of W. pigra spawning and hatching were observed under different temperatures and weights conditions. RESULT AND CONCLUSION: 25 degrees C is the most appropriate temperature for W. pigra spawning and incubation, the best spawning weight of W. pigra was around 20 g. The temperature influenced the lost weight after spawning significantly and was proportion to the lost weight. The body weight showed no substantial influence to the lost weight after spawning. The egg weight of W. pigra which body weight was below 2.0 g was proportion to the hatching rate. The same relationship was not observed in W. pigra over 2.0 g. PMID- 17357548 TI - [A new molecular method to authenticate radix trichosanthis as well as its adulterants and substitutes]. AB - OBJECTIVE: To explore a new molecular method to authenticate Radix Trichosanthis. METHOD: Three 20 mer primers based on the ITS sequence was designed. The PCR reaction system was optimized and applied to nineteen different sources of Radix Trichosanthis and nine adulterants and substitutes. RESULT: Polymorphic map of Radix Trichosanthis and its adulterants was obtained from primer TKS1-64. 560 bp and 960 bp bands were authentic markers for Radix Trichosanthis. CONCLUSION: Primer TKS1-64F possesses the advantages of good stability and reproducibility. This new method is named as anchored primer amplification polymorphism DNA(APAPD). It was a potential method to used in molecular identification of other meteria medica. PMID- 17357549 TI - [Simultaneous determination of six main constituents in Swertia of Qinghai Province and Sichuan Province by HPLC]. AB - OBJECTIVE: To establish a quantitative method of simultaneously determination of swertiamarin, gentiopicroside, mangiferin, swertianolin, isoorientin, 1,8 drihydroxy-3-methoxy-xthanone in Swertia from Qinghai province and Sichuan province by HPLC. METHOD: The samples were separated on the column of Kromasil C18 (4. 6 mm x 250 mm, 5 microm) which eluted with methanol and water (content 0.02% phosphoric acid). The ratio of methanol increased from 20% to 80% during 20 50 min, and from 80% to 100% during 50-60 min, with detected wavelength 254 nm, flow rate at 1 mL x min(-1), column temperature 35 degrees C. RESULT: Six compounds were base-isolated, the linear ranges of swertiamarin, gentiopicroside, mangiferin, 4-swertianolin, 5-isoorientin, 1,8-drihydroxy-3-methoxy-xthanone were excellent. CONCLUSION: The method was rapid and precise, and can be use for controlling medicinal materials quality. PMID- 17357550 TI - [Preparation of inclusion complex of daidzein and hydropropyl-beta-cyclodextrin]. AB - OBJECTIVE: To prepare an inclusion complex of daidzein and hydropropyl-beta cyclodextrin to enhance the solubility of daidzein. METHOD: The inclusion complex of daidzein was prepared by the solution stirring method. The binary system of daidzein and HP-beta-CD was confirmed by differential thermal, thermogravimetry analysis, infrared spectroscopy and X-ray diffractometry. RESULT: The drug content in the inclusion complex was 6. 76% and the solubility was 13.68 mg x mL( 1). The identification results showed that the inclusion complex was formed. CONCLUSION: The preparation method of the inclusion complex of daidzein and hydropropyl-beta-cyclodextrin is simple and available, with a increased solubility of daidzein. PMID- 17357551 TI - [Study on uniform-design for optimizing supercritical-CO2 fluid extraction technique of tanshinones in radix salviae]. AB - OBJECTIVE: To explore the optimal supercritical-CO2 fluid extraction technique of extracting tanshinones in Radix salviae. METHOD: The contents of tanshinones were determined by HPLC. Choosing the overall contents of 3 tanshinones as inspecting marker and uniform-design as method, the experimentation was carried out to study the main factors that influence the result of extraction. RESULT: Among all the 5 inspected factors, the amount of entrainer was most notable. The optimal technique of extraction was: extraction pressure at 30 MPa; extraction temperature at 40 degrees C; separation pressure of separating kettle I at 6 MPa; separation temperature of separating kettle I at 50 degrees C; the amount of entrainer at 10%. CONCLUSION: Adopting supercritical-CO2 fluid extraction method to extract the tanshinones in Radix salviae was feasible. The contents of tanshinones in the extract were high and the manipulation was simple, convenient and time saving. PMID- 17357552 TI - [Norisoprenoids from red alga Gymnogongrus flabelliformis]. AB - OBJECTIVE: To investigate the chemical constituents of the red alga Gymnogongrus flabelliformis Harv. METHOD: Compounds were isolated by normal phase silica gel and Sephadex LH - 20 gel column chromatography and reverse phase HPLC. Their structures were elucidated by spectroscopic methods including MS, 1H-NMR, 13C NMR. Cytotoxicity of the compounds was screened by using standard MIT method. RESULT: Five compounds were isolated from G. flabelliforrmis, their structures were identified as(3S, 6R, 7E)-( + )-3-hydroxyl-4, 7-mega-stigmadien-9-one (1), (3S, 5R, 6S, 7E)-(-)-3-hydroxy-5, 6-epoxy-7-megastigmene-9-one (2), (3S, 5S, 6R, 7E)-(+)3-hydroxy-5, 6-epoxy-7-megastigmene-9-one (3), dehydrovomifoliol (4), (3R) (-)4-[(2R, 4S)-4-acetoxy-2-hydroxy-2, 6, 6-trimethylcyclohexylidene] -3-buten-2 one (5). CONCLUSION: All of the compounds were obtained from this species for the first time and compound 1 was a new natural product. These compounds were inactive (IC50 > 10 microg x mL(-1)) in the MTT assay against several human cancer cell lines. PMID- 17357553 TI - [Studies on chemical constituents from fruits of Paliurus ramosissimus]. AB - OBJECTIVE: To study the chemical constituents from the fruits of Paliurus ramosissimus. METHOD: The constituents of P. ramosissimus were separated with various chromatographic techniques and their structures were elucidated by means of spectral analysis and physico-chemical properties. RESULT: Nine compounds were isolated and identified as umbelliferone (1), scoparone (2), aurapten (3), bergapten (4), isopimpinellin (5), byakangelicin (6), xanthotoxol (7), isosakuranin (8), poncirin (9). CONCLUSION: Compounds 1-9 were isolated from the fruits of P. ramosissimus for the first time. PMID- 17357554 TI - [Study on chemical constituents of mangrove Acanthus ilcifolius]. AB - OBJECTIVE: To study the chemical constituents of Acanthus ilicifolius. METHOD: Chromatographic methods were used to isolate compounds from A. ilicifolius, and chemical and spectroscopic methods were used to elucidate the structures of the isolated compounds. RESULT: Seven compounds, betaine (1), phenylethyl-O-beta-D glucopyranosyl- (1-->2) -beta-D-glucopyranoside (2), phenylethyl-O-beta-D glucopyranoside (3), acteoside (4), isoacteoside (5), benzyl-O-beta-D glucopyranoside (6) and vanillic acid (7) were obtained. CONCLUSION: 1, 3, 6 and 7 were obtained from the genus for the first time. PMID- 17357555 TI - [Studies on GC fingerprint of volatile oil of Houttuynia cordata]. AB - OBJECTIVE: To establish a GC fingerprint of the volatile oil of Houttuynia cordata. METHOD: The volatile oil was extracted from H. cordata by water stream distillation method, and analyzed by GC coupled with FID. RESULT: 12 bathes of samples collected from different regions were analyzed; the GC fingerprint of the volatile oil of H. cordata was subsequently established. CONCLUSION: The established GC fingerprint can be used for the identification of H. cordata. PMID- 17357556 TI - [Experimental study of chronic kidney failure delayed by Xinshen capsule]. AB - OBJECTIVE: To evaluate the effect of Xinshen capsule upon the chronic kidney disease progress by the study of 7/8 kidney removal rat model. METHOD: The urea nitrogen and the blood creatinine level were estimated by automatic biochemistry analyzer. Hemorheological index level was measured by rheometer. Urine protein was measured by Coomassie brilliant blue. PAS and PASM staining was applied to observe kidney histology change, and semi-quantitative analysis was used to observe the kidney histology change. RESULT: In model control group, the urine protein excretory rate and the urea nitrogen, the blood creatinine level were up regulated obviously, erythrocyte aggregation index and whole blood viscosity value were down-regulated significantly, kidney organizations show up pathological change evidently, and leave surgical group compared the difference. After the treatment of Xinshen capsule, the above indicators are improving obviously. CONCLUSION: Xinshen capsule can degrade urine protein, the urea nitrogen and the blood creatinine level, and lower red blood cell accumulation and the whole blood viscosity, alleviate kidney various pathological change, the medicine can effectively delay the progress of chronic kidney disease. PMID- 17357558 TI - [Effect of five species of Epimedium on growth of cartilage and proliferation of cartilage cell in vitro]. AB - OBJECTIVE: To observe the effect of Epimedium brevicornum, E. sagittatum, E. koreanum, E, wushanense and E. elongntum on the growth of cartilage and proliferation of cartilage cell in vitro. METHOD: According to the paired design method, either femur of each chichen embryo was put into the control tube with the medium containing no Epimedium injection, and the other was put into the treated tube with the medium containing 3% Epimedium injection. The length and weight of cultured cartilage and proliferation of cartilage cell (MTY method) were used as the indices to observe the cartilage biological activities of the five species of Epimedium in culture. RESULT: The results showed that the indices of length, weight and MTT in the E. brevicornum and E. sagittatum group were significantly higher than those in the contral group, but the above indices in groups E. koreanum, E. wushanens and E. elongntum were similar to those of the control with no statistical difference. CONCLUSION: E. brevicornum and E. sagittatum can improve the growth of cartilage and proliferation of cartilage cell in vitro, and other three Epimedium have not the same effect in this test. PMID- 17357557 TI - [Experimental studies of rhizoma Astilbes chinensis on its effects in abirritation, blood activation, cough relieving and sputum elimination]. AB - OBJECTIVE: To study the effects of rhizoma Astilbes chinensis in abirritation, blood activation, cough relieving and sputum elimination. METHOD: The antalgic function of rhizoma A. chinensis was tested by hot-plate method and writhing reaction. The acute blood-stasis model rats were made by Injection of adrenaline hydrochloride along with stimulation by ice water. The effects of cough relieving and sputum elimination were observed by the ammonia water-induced tussive mice and excretion of phenol red in the airway of mice. The maximum tolerance dose of rhizoma A. chinensis was also determined during the acute toxicity test. RESULT: The data were analyzed for statistical significance by t-test, which shows that the decoction of rhizoma A. chinensis is significantly effective in reducing the frequency of licking behavior of mice on hot-plate and writhing response induced by acetic acid, improving the hemarheology of acute blood-stasis model rats, prolonging the latent period, reducing the frequency of cough induced byammonia, and in increasing the quantity of phenol red output from the trachea in mice. The result acute toxicity test shows that maximum tolerance dose of gastrogavage in mice was 400 g x kg(-1). Which was 666. 7 times of that clinically used for human. CONCLUSION: Rhizoma A. chinensis has the effects of abirritation, blood activation, cough relieving and sputum elimination, and is safe in clinical application. PMID- 17357559 TI - [Effect of Qianjin Fubao on changes of behavior and estradiol level in chronic stress model rats]. AB - OBJECTIVE: To investigate the effect of Qianjin Fubao (QJFB) on behavior and estradiol level in femal chronic stress model rats. METHOD: Twenty four female Wistar rats (2 month old) were evenly randomized into normal control, animal model and QJFB (0.7 g x kg(-1) x d(-1)) group. The QIFB group and the stress group were exposed to a chronic unpredictable stress for 21 days. Rats of the QJFB group received perfusion of Qianjin Fubao, and rats of stress and control group were perfused with normal saline. The behavior of three groups were determined with the method of Open-field before and after right stress respectively. Serum level of estradiol was detected with radioim munoassay. RESULT: The behavioral score and the serum level of estradiol of the stressed group were significantly lower than those of the control group after stress (P < 0.05). There were no significant differences of behavioral score and the serum level of estradiol between QJFB group and control group. CONCLUSION: The chronic unpredictable stress can induce the stressful change of behavior, and QJFB may recover the rats'abnormal behavior and improve the serum level of estradiol. QJFB may have protective effect on stress. PMID- 17357560 TI - [Cure effects of Jiangu Fufang on osteoporotic model induced by ovariectomy]. AB - OBJECTIVE: To explore the cure effects of Jiangu Fufang on osteoporotic model induced by ovariectomy. METHOD: Rats were ovariectomized and administered drugs for 3 monthes. Bone mineral density and biomechanics properties, histomorphometric analysis and biochemical index such as calcium, phosphorus, alkaline phosphatase were detected. RESULT: Jiangu Fufang could significantly increase bone density and biomechanics properties. The level of calcium, phosphorus and alkaline phosphatase were restored by Jiangu Fufang. Jiangu Fufang could significantly increase area of bone trabecula, thickness of cortical bone and bone trabecula. CONCLUSION: Jiangu Fufang could cure osteoporosis through increasing bone mineral density, improving bone biomechanics properties, and effecting bone metabolism. PMID- 17357561 TI - [Allergy in Mexico and at Hospital Infantil de Mexico]. PMID- 17357562 TI - [Normal values of peak expiratory flow in 6-15 year-old healthy children of Puebla's city]. AB - BACKGROUND: The peak expiratory flow (PEF) is a clinical tool for the evaluation of flow pulmonary, integrated in many studies and guides for the management of asthma, so it is important to have references about its normal values in healthy children Puebla's city. MATERIAL AND METHODS: We did an observation, descriptive, transversal and prospective study, where we evaluated to 1154 children from Puebla's city and peak expiratory flow measurements were obtained. RESULTS: The mean values by stature and sex for PEF were dispersed in both sex, the average for males were of 286 L/min, females 251 L/min, finding the major average value in males, with Z = 0.6946 level to confidence of 80%, so the PEF was major in males. We compared variations; and the value of the proof of Fisher was 1.12 with a level of confidence of 90%. The lineal regression straight was: males B1 = 5.3 and B0 = -481, females B1 = 4.82, B0 = -436. The correlation between height and peak expiratory flow was: males R2 = 0.8283, females R2 = 0.7652, for the standard mistake it was calculated with the sum of square of mistakes and the number of observations corresponding for males 22.6% and females 20.3%. CONCLUSIONS: The values of healthy children's PEF in Puebla's city are different to other experiences. By first time we have reference values of PEF in healthy children of Puebla's city by sex and height. PMID- 17357563 TI - [Frequency of Helicobacter pylori infection in patients with chronic urticaria of Puebla University Hospital]. AB - BACKGROUND: Chronic urticaria may be continuous or recurrent according to its form of appearance. Within the diseases associated to chronic urticaria there are mycosis, parasitism and bacterial infections where Helicobacter pylori stands out. This has been related to the allergic diseases promoting a Th2 response. OBJECTIVE: To determine the frequency of infection caused by Helicobacter pylori in patients with chronic urticaria of the allergic and clinical immunology service of the Puebla University Hospital. PATIENTS AND METHODS: A descriptive, cross-sectional, prolective and observational study was made in adult patients, between 18 and 60 years old, with diagnosis of chronic urticaria. Inhalated and food skin prick test were made to all the patients. The infection by Helicobacter pylori was documented by serology, fecal antigen, endoscopy with fast test of urease and histological study. Descriptive statistics was implemented such as frequency, percentage, central tendency and dispersion measures. RESULTS: 30 patients were included; 83.3% were women. The average age was 37.8 years (SD 13.2). The most frequent type of chronic urticaria was the persistent one, representing 56.7%. The frequency of positivism of IgG antibodies against Helicobacter pylori represented the 60.0%, for IgM 33.3% and for fecal antigen 60.0%, the combined IgG, IgM, fecal antigen, fast test of ureasa and histological study was of 83%. CONCLUSION: The high frequency of infection caused by Helicobacter pylori in the patient with chronic urticaria suggests a possible role in its etiopathogeny, extending the therapeutic possibilities. PMID- 17357564 TI - [Prevalence of allergy to drugs in a group of asthmatic children and adolescents of northeast of Mexico]. AB - BACKGROUND: Drug adverse reactions are a common cause of morbidity and they constitute an important challenge in medical practice. The allergic reactions represent only a small proportion of all the drug adverse reactions and although their real prevalence is unknown, some estimated numbers have been suggested. It seems that atopia is not a risk factor for the development of this kind of reactions. PATIENTS AND METHODS: A cross-sectional descriptive study was performed to assess the prevalence of drug allergy in asthmatic children of the northeast of Mexico that attend summer camps. We investigated the history of drug adverse reactions and their clinical features in 90 atopic asthmatic patients from 5 to 15 years old which were evaluated trough a questionnaire that was completed by their parents. RESULTS: Eight of the 90 evaluated patients (8.8%) had history of adverse reactions to some drug. The drugs involved in that reactions were: penicillin in four patients (50%), aspirin in 2 (25%), trimethoprim and sulfamethoxazole in one (12.5%) and metamizole sodium in one (12.5%). The most common administration route was oral. In all of the cases the diagnosis was made on clinical basis. One of the patients had suffered from anaphylaxis, but in the other seven, urticaria was the unique clinical manifestation of the reaction. In all of the affected patients, the reactions were totally resolved in less than 48 hours. CONCLUSIONS: The prevalence of drug allergy in this group was similar to that reported in general population. Penicillin was the most common involved drug and urticaria was the most frequent clinical manifestation. PMID- 17357565 TI - [Superantigens and toxic shock syndrome. A report of three cases treated with intravenous gammaglobulin]. AB - The superantigens cause a massive polyclonal activation of T-cells, producing an immense liberation of proinflamatory cytokines, which induces the clinical data of toxic shock syndrome. In international studies the administration of polyclonal intravenous gammaglobulin has been observed to diminish the mortality 50 to 20%. But at the present it has not been reported in Mexico the clinical effectiveness of this therapeutic modality in toxic shock syndrome. We report three cases of toxic shock syndrome treated with gammaglobulin intravenous, and we describe their favorable clinical evolution. PMID- 17357566 TI - [Atypical presentation of hereditary angioedema. A report of a case and literature review]. AB - Hereditary angioedema is an uncommon disorder mainly caused by defects of the gene for C1 inhibitor. These patients present recurrent edema episodes in the different regions of the body, including larynx edema in some cases. Low plasma levels of C1 inhibitor confirm the diagnosis. It is important to establish an early diagnosis and prompt treatment to this disorder due to its potential of fatal consequences and multiple alterations in the quality of life that have been associated with. The indicated treatment is substitutive therapy of C1 inhibitor concentrate. We present the case of a patient a 27 year-old female with a history of seven years of evolution, with daily periorbital, upper and lower extremities and labial edema episodes who was classified as C1 inhibitor deficiency type II. She began treatment with attenuated androgens in progressive increased doses with poor response, appearing torpid evolution without a favorable response. This case corresponds to a very atypical presentation of C1 inhibitor deficiency with daily symptoms, unlike the typical intermittent course of the classic disease. PMID- 17357567 TI - Cryptococcus neoformans and Histoplasma capsulatum in dove's (Columbia livia) excreta in Bolivar state, Venezuela. AB - Dove's excreta samples from state Bolivar several places in Venezuela, were evaluated to determine the presence of primary pathogen fungi in dove's excreta. Filamentous fungi such as: Aspergillus spp (31.1%), Mucor spp (20.2%), Penicillium spp (9.5%) and Fusarium spp (6.7%) were the most frequently isolated strains. Species such as Candida albicans (4.1%), Cryptococcus albidus and Rhodotorula spp (2.7%), C. neoformans var neoformans (1.4%), Trichosporum asahii (1.4%), Curvularia, Microsporum and Phoma as well as Histoplasma capsulatum (1.3%) were less frecuently isolated. This study shows the presence of C. neoformans and H. capsulatum in dove's excreta from Bolivar state, it remarks infection risk with these pathogens fungi and the necessity to avoid accumulation of dove's excreta. PMID- 17357568 TI - Incidence of salmonellosis and identification of serogroups and serotypes in a pig commercial farm in Yucatan. AB - A study was conducted in order to detect the presence of Salmonella spp in fattening pigs, to identify the serogroups present and to determine the sensibility to the antibiotics more used in the region. The farm was a breeding farm of a multiple-site system. Of the total farrowings of a week, 55 sows and one piglet from each sow were selected. All pigs were negative to Salmonella spp. at the star of the study. Piglets were monitored from day two of age (six times; every 23 days approximately) up to finishing (23 weeks of age). Samples of feces (1 g/animal) were collected directly from the pig's rectum. The first positive pig was found at the second sampling (25 days) and the highest number of positive cases in the fifth sampling (117 days). The cumulative incidence was 52.7%. Thirty-four out of the 40 Salmonellas isolated corresponded to the B serogroup and 6 to the C2 serogroup. The serotypes found in the B serogroup were: S. typhimurium (28/34) and S. agona (6/34). Regarding serogroup C2 these were: S. romanby and S ajiobo. Salmonella spp B serogroup included three of the serotypes more commonly isolated in humans: S. typhimurium, S. agona and S. heidelberg. PMID- 17357569 TI - Antimicrobial susceptibility of strains of Propionibacterium acnes isolated from inflammatory acne. AB - In the last decade, a significant increase in the antimicrobial resistance of clinical specimens of Propionibacterium acnes to first line antibiotics used for acne treatment, has been informed in Europe and in the USA. No information about strains isolated from Latin-American countries is available. The antimicrobial susceptibility of 53 strains of P. acnes isolated from skin specimens of inflammatory acne patients, at the clinical Hospital University of Chile was tested. All isolates were susceptible to penicillin, minocycline, and nadifloxacin. Erythromycin and clindamycin resistance was found in 3.8 and 1.9% isolates respectively. Resistance to lymecycline was observed in one isolate, which was intermediate to tetracycline and doxycycline. PMID- 17357570 TI - Virus diversity of acute diarrhea in tropical highlands. AB - Infectious acute diarrhea (IAD) is an important health problem affecting a large number of Latin-American children. Several reports show that bacteria, parasites and virus are involved in the burden of this disease. Most reports reveal Rotavirus A as the responsible etiological agent, at the same time, there seems to be some correlation between IAD and seasonal weather changes. To learn about the type of microbial agents associated with IAD in children during mildly changing yearly climatic conditions, as found in a high altitude tropical city, and to identify the viral agents affecting this population, stool samples from 300 children under 5 years of age were studied throughout a one-year period. Bacteria and intestinal parasites were identified by routine methods, while viruses were detected and typed by EIA and PCR. 20.6% of the IAD studied was associated with bacteria; 9% with parasites and 40% with virus. Group C Rotavirus accounted for 20.2%, group A Rotavirus for 13% and Calicivirus 10%. During November-April (p < 0.007) more virus associated IAD was found, while bacteria (p < 0.03) or parasite (p < 0.00014) related IAD was prevalent from May to October. The mild seasonal weather changes don't seem to be associated with any other microbial agent. PMID- 17357571 TI - Chromosomal-gene-mediated inhibition of intestinal and foodborne pathogens by Lactobacillus acidophilus AA11. AB - Approximately 63 strains of Lactobacillus acidophilus were isolated from Egyptian home-made cheese and examined for production of antagonism. Only eight strains demonstrated inhibitory activity against spoilage microorganisms (i.e. Staphylococcus aureus and Bacillus cereus) and pathogens (i.e. E. coli, Salmonella sp. and Shigella sp.). Lactobacillus acidophilus AA11 produced a more antimicrobial activity with a wide range of inhibition. The agent AA11 was sensitive to proteolytic enzymes and retained full activity after 30 min at 100 degrees C. Activity against sensitive cells was bactericidal but not bacteriolytic. The compound was produced during growth phase and can be extracted from the culture supernatant fluids with n-Butanol. 12 % SDS-PAGE analysis of 40% ammonium sulphate precipitated agent showed two peptides with molecular weights of approximately 36 kDa and approximately 29 kDa. No plasmid was identified in Lactobacillus acidophilus AA11 indicating that the genes encoding the inhibitory agent located on the chromosome. These characteristics identify the inhibitory substance as a bacteriocin, designated acidocin AA11 and confer the agent an application potential as a biopreservative. PMID- 17357572 TI - [Co-evolutionary strategies of interaction between parasitoids and polydnaviruses]. AB - Polydnaviruses are genetic symbionts of wasp endoparasitoids belonging to the hymenopteran families Ichneumonidae (ichnoviruses) and Braconidae (bracoviruses). They exist as proviruses integrated in the wasp's chromosomal genome, which then excise and undergo replication during the stage of adult development of the wasp. During wasp oviposition into their caterpillar host, the fully formed virus particles are injected along the parasitoid's eggs into the host hemocoel, where the eggs hatch and undergo larval development. The primary function of the polydnavirus is to trigger host immunosuppression so that host hemocytes are prevented from encapsulating the parasitoid's eggs and/or larvae. Polydnavirus transcripts are expressed following parasitization and alter host hemocyte adhesive properties that prevents encapsulation; in some species, viral gene expression triggers host hemocyte apoptosis, thereby rendering the host immunosuppressed. This review summarizes the major features of polydnaviruses and provides a global view of their functions in the lepidopteran hosts of the parasitoid wasps that carry them both as integrated viral sequences in their genome and as free virus to function physiologically in host regulation following parasitization of the host. PMID- 17357573 TI - The post-genomic era--what comes next? PMID- 17357574 TI - [Clinical experience of combined oral contraceptives of low doses in Mexico]. AB - BACKGROUND: The combined oral contraceptives are one of the most prescribed medicines. Across the years they have given to more than 60 million women of the whole world a suitable method for the highly reliable and effective natal control. The oral contraceptives are different from other medicines; principally they are not in use for controlling any disease and have the potential of giving advantages. OBJECTIVES: To evaluate the control of the cycle, tolerability and acceptance of an oral contraceptive of ultralow dose with gestodene (60 microg) and ethinylestradiol (15 microg) in a population of healthy women from 18 to 35 years. PARTICIPANTS AND METHODS: The study included adult healthy women, all the users signed assent of informed before being included to the study and of the beginning of any procedure in agreement with the declarations of Helsinki and its amendments. Descriptive statistics was used for the demographic information and the comparison between the initial and final visits of the variables of efficiency. There was used the test (Proof) of ranges of Wilcoxon's sign for related samples. RESULTS: There were included 113 women. The average of age was 26.08 years (SD = 4.43), weight of 62.02 kg (SD = 11.13) and height of 159.20 cm (SD = 6.06). The distribution in four centers was: 32 in the University Hospital (Monterrey), 21 in the Country 2000 (Guadalajara), 30 in in the Medical Center La Mora (Aguascalientes) and 30 in Perinatology National Institute (Mexico City). CONCLUSIONS: The contraceptive efficiency of the combination of 15 microg of ethinylestradiol and 60 microg of gestodene has been demonstrated in previous studies. This study ratifies the international results of efficiency and tolerability. PMID- 17357575 TI - [Early menarche as a risk factor of breast cancer]. AB - BACKGROUND: Most of the information in medical literature report diverse factors of breast cancer, which are related to the reproductive life of the woman. It is mentioned that menarche before the 12 years elevates the relative risk of this disease, in comparison with its appearance after the 13 years. OBJECTIVE: To determine if early menarche is a risk factor associated to breast cancer. MATERIAL AND METHODS: This retrospective, observational and descriptive study included 162 women with breast cancer from a 3 years period (2002-2004), in the Juarez Hospital of Mexico. In addition other well known risk factors for breast cancer were evaluated. The statistical analysis was made with the software program SPSS; the descriptive analysis was made by means of summary of statistics, histograms, box and bar charts. RESULTS: Early menarche doesn't have correlation with breast cancer nor with the appearance of the disease in early ages; it was present in the 12.3% (n = 20) of the patients; the menarche initiated between 12 and 13 years in 64.4% (n = 104.3) of the cases. The average age at the time of the diagnosis of breast cancer in the early menarche group was of 55 years and for the group in general of 47.6 years. The factor that seems to be related to breast cancer is overweight and obesity with 54.26 and 17.11% respectively, with an average body mass index of 27.7 kg/m2. CONCLUSIONS: There was not a correlation between early menarche as risk factor for breast cancer neither between the reproductive risk factors considered habitual and increased risk of breast cancer. Overweight and obesity seem to be related to the appearance of the disease, reason why it is required to investigate this with different random control groups in the country. We propose to study other factors that may be implicated in the genesis of breast cancer such as inflammatory factors, similar insulin growth factors and hyperinsulinism. PMID- 17357576 TI - [Prenatal risk factors in late fetal death]. AB - OBJECTIVE: To identify the sociodemographics, obstetrical and perinatology factors of risk most frequently associated to fetal death in greater pregnancies of 27 weeks. PATIENTS AND METHODS: From January 2001 to May 2005, in the Hospital Civil de Guadalajara Dr Juan I. Menchaca, we carried out a study of cases and controls with 450 cases of fetal death of more than 27 weeks of gestation and 450 newborn alive whose birth happened immediately later. We compared the frequency of different maternal and fetal variables that in previous forms was associated with fetal death, by means of Chi squared test and exact test of Fisher, the association among these variables and fetal death with the reason of momios was considered. In all the cases the chosen interval of confidence was of 95%. RESULTS: The risk factors associated with fetal death were: maternal age over 35 years, low schooling, multiparity, antecedent of abortion and fetal death, deficient prenatal care, complications in the pregnancy, abnormal amniotic fluid, double circular of umbilical cord to neck of the product and great congenital malformations of newborn. It was not associated with fetal death, the single marital status, primigesta, smoking, male sex of the fetus, simple circulate of umbilical cord to the neck and fetal macrosomia. CONCLUSIONS: Of the risk factors associated with fetal death, the main one is a deficient prenatal care, that of being improved, might diminish the association of some other variables that were associated with fetal death. PMID- 17357577 TI - [Effect of alpha dihydroergocryptine in patients with fibrocystic breast disease]. AB - OBJECTIVE: To evaluate the effectiveness of alpha dihidroergocriptine in patients with fibrocystic mastopathy. PATIENTS AND METHODS: Patients with diagnosis of fibrocystic breast disease were included in a prospective longitudinal blind double, controlled with placebo study. Patients were randomly assigned to one of two treatment groups: of treatment group A: Alpha dihidroergocriptine tablets of 10 mg, group B: Placebo, during 6 months. After to basal evaluation, the patients were revised in a monthly way evaluating the following symptoms and signs: mastalgia, mammary tension, presence of nodules, nipple secretion, and the presence of adverse events. RESULTS: 39 patients with alpha dihidroergocriptine and 38 with placebo. Mastodinia, a satisfactory response was observed in 100% of alpha dihidroergocriptine group vs 61.11% of placebo group (p = 0.0002). Mastalgia responded in 100% of alpha dihidroergocriptine group vs 64.86% of placebo group (p = 0.0003). Galactorrea responded 100% of alpha dihidroergocriptine group vs 93.33% of the placebo. The nodules in the group alpha dihidroergocriptine disappeared in 23.1% and in 21.1% of the placebo group. Ultrasound evaluation of the nodules did not show significant differences between both groups. Prolactin levels showed a decrease in the group treated with alpha dihidroergocriptine with an important difference between both groups at the end of the 6 months study period. There were not differences in the presence of adverse events between groups. CONCLUSIONS: Alpha dihidroergocriptine is effective in the treatment of fribrocystic breast disease with minimum adverse events when compared with similar drugs. PMID- 17357578 TI - [Epidemiology of breast cancer]. AB - Breast cancer is the most frequent malignant tumor worldwide. In recent years there has been observed an increase in its frequency, especially in developing countries, as Mexico, where mortality is arriving to the first cause of death in females. This is, in part, due to a delayed diagnosis, most frequently done in locally advances stages with a low cure rate. This is a review of all risk factors: age, sex, personal and familial history, genetic syndromes, associated breast disease, geographic distribution, body structure and environmental, hormonal, reproductive and dietary factors. It is concluded that breast cancer is a public health problem in developed and developing countries, and the best methods to drop mortality for breast cancer is the wide use of screening mammography in women at risk, in order to find cancers at initial stages and offer the adequate treatment. PMID- 17357579 TI - [Cervical pregnancy. A report of a case and literature review]. AB - The cervical pregnancy is a rare clinical illness among the ectopic pregnancies; the diagnosis at the moment is made by means of ultrasonography, which shows an empty uterus and a gestation in cervical channel. At the moment the preservative treatment can be made with methotrexate, without determining of precise way the factors of fault for this handling, leaving the single surgical treatment in emergency situations, avoiding the uncontrollable haemorrhage. This paper reports the case of a patient with a cervical pregnancy of nine weeks, live, with initial determination of corionic gonadotrophin hormone of 68,919 mUl/mL; reason why it is decided to interrupt the gestation being applied two doses of methotrexate; first IV of 85 mg and second with intraamniotic application. The evolution of the gestation was towards the involution and absorption of the gestational coat, the sub-unit concentrations corionic gonadotrophin hormone beta presented decrement, until undetectable, with good clinical and functional results. The gestational coat was reduced, the embryo lost beat and the gonadotrophin were in decrement until zero, with clinical evolution with stained solely haematic, without haematological and functional repercussions. Criteria of fault of the preservative treatment with methotrexate are not defined, although due the peculiarity of this illness, it is not possible to make a more extensive study, but by the reproductive benefit in young patients, it would be adapted to take it in to account like option instead of the hysterectomy. PMID- 17357580 TI - [Placenta previa-accreta: a singular problem. A report of two cases and bibliographic review]. AB - Placenta previa in women older than 34 years old with previous cesarean section has a high risk to develop placenta accreta/inccreta/perccreta. Such background is frequent nowadays, so placenta previa-accreta is a growing problem. This disease cause hypervascularity in the pelvic floor and increases the risk of placenta penetrating the bladder. For these peculiarities, the maternal morbidity and mortality are higher; besides, hysterectomy produces additional morbidity and mortality. For such reasons, experts explore at present other alternatives to be able to make a better maternal prognosis. In this article we report two cases with placenta previa-accreta, and make a review of medical literature about this topic. PMID- 17357581 TI - [Congenital gynecological processes that may produce sterility or infertility and the role of surgery on them 1951 (classical article)]. PMID- 17357582 TI - Molecular medicine of the future--applications and pitfalls. PMID- 17357583 TI - Asymmetric syntheses and transformations--tools for chirality multiplication in drug synthesis. AB - A review of currently used methods for the synthesis and resolution of enantiomers of drugs and their precursors is presented. For the synthesis part the methods of diastereoselective as well as enantioselective synthesis are discussed, with particular consideration given to enantioselective catalysis with either metal complexes or biocatalysts. Desymmetrization processes are also included as methods to access enantiomerically pure compounds. Racemate resolution still remains an important method to obtain pure enantiomers and methods involving kinetic resolution in enzymatic or chemical systems, and particularly in connection with racemization (dynamic kinetic resolution) are on the rise in fine chemical industry, when applicable. PMID- 17357584 TI - Biodegradable nano- and microparticles as carriers of bioactive compounds. AB - This review presents examples of polymeric carriers that may be used for design of clinically aplicable drug delivery systems. In particular, there are discussed methods suitable for protein and oligopeptide modification in a way making these molecules "invisible" for immune system of an organism into which they are introduced. Presented are methods of synthesis of block copolymers suitable for self-assembly into nanoparticles loaded with bioactive compounds. There are discussed also strategies used for obtaining microparticles loaded with bioactive compounds either from earlier synthesized polymers or from monomers, directly during polymerization. PMID- 17357585 TI - New targets for putative neuroprotective agents. AB - A better understanding of intracellular pathways engaged in the neuronal cell death afforded us new targets for developing putative neuroprotectants. Also pharmacological or genomic intervention aimed to modulate the expression of endogenous neuroprotective or toxic agents is a very promising strategy. Taking into account enormous complexity of biochemical cascades involved in neurodegenerative processes, multipotential or combined pharmacological approaches seem to be more efficient in combating degenerative brain diseases. Moreover, an improved cell transplantation also adds to a plethora of methods, which are used to afford neuroprotection and promote neurorestoration. All those strategies are reviewed in the presented article. PMID- 17357586 TI - Cancer chemopreventive agents-drugs for the 21st century? AB - After a quarter of a century of rapid advances in cancer research, the focus of oncological drug development has shifted from cytotoxic chemotherapy to rationally designed agents that target specific molecules associated with malignant cells or their environment. Carcinogenic process is driven by mutation, but there are many epigenetic variables which could be the targets of early intervention before invasion and metastasis occur. Chemoprevention is the inhibition, retardation or reversal of carcinogenic processes by pharmacological or natural agents targeting these pathways in high-risk individuals. This approach was developed more than 30 years ago and its credibility was enhanced by the positive results of clinical trials involving subjects with risk of developing breast cancer and colon tumors. So far however, not many clinical trials provided satisfying results, not only because of the lack of efficacy or side toxic effects of chemopreventive agents, but also the lack of precise biomarkers monitoring their effects. In spite of all these obstacles, the field of cancer chemoprevention is very active, not only because of its accelerating scientific base, but also because is vitally needed. New information from molecular studies has identified specific molecular targets for chemopreventive agents. These include regulatory molecules such as Nrf2, epidermal growth factor receptor kinases, components of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, nuclear factor-kappaB, and cyclin D. The development of new drugs for the control of these targets that are both safe and effective will be important for the future of cancer chemoprevention. PMID- 17357587 TI - Synthesis and antibacterial activity of 5-adamantan-1-yl-methyl analogues of trimethoprim. AB - A series of new trimethoprim [5-(3,4,5-trimethoxy-benzyl)-pyrimidine-2,4- diamine] analogues were prepared by condensation of adamantane-1-carbaldehyde with 3-methoxypropionitrile, followed by reaction of resulting mixture of 2 adamantan-1-ylmethyl-3-methoxy-acrylonitrile and 3-adamantan-1-yl-2-methoxymethyl acrylonitrile with guanidine, acetamidine and thiourea, respectively. The activity of compounds obtained and sulfamethoxazole, alone and in combination, against several bacterial strains, as well as fungi was investigated. PMID- 17357588 TI - The biological activity of new tuftsin derivatives--induction of phagocytosis. AB - Phagocytosis plays a crucial role in a host defense against invading microorganisms. This process can be induced by many phagocytosis stimulating factors. One of them is an endogenous tetrapeptide - tuftsin that occurs in the blood of mammals including human beings. Tuftsin is capable of potentiating granulocyte and macrophage functions such as: phagocytosis, motility, and chemotaxis as well as bactericidal and tumoricidal activity. The other particle able to induce phagocytosis is muramyl dipeptide (MDP), the smallest synthetic glycopeptide of bacterial origin that possesses an immunogenic activity. MDP is known to affect most functions of macrophages. Phagocytosis stimulating properties of a new group of tuftsin and MDP analogues (one tuftsin analogue and four conjugates of tuftsin/retro tuftsin and muramyl dipeptide or nor-muramyl dipeptide) were tested. The results of the study show that all of the examined conjugates are able to generate oxidative burst. The most promising analogues proved to be kd6 and kd7. PMID- 17357589 TI - Biotransformation of praziquantel by human cytochrome p450 3A4 (CYP 3A4). AB - Praziquantel (PZQ) is the drug of choice for the treatment of human schistosomiasis. It is estimated that about 200 million people in the world are currently affected by this tropical disease. Now PZQ is also used in malaria treatment. The usefulness of PZQ as antimalarial drug is important because of rapid development of resistance to usually applied drugs. PZQ undergoes extensive metabolism in human body, mainly in liver by two cytochrome P-450 isoenzymes 2B1 and 3A. As the result of these biotransformations numerous mono- and dihydroxylated derivatives in B, C and D ring are formed. Two metabolites have been fully identified and described, as cis- and trans-4-hydroxypraziquantel. Up to now there were created many different in vitro and in vivo models of PZQ biotransformations. In vitro model of PZQ biotransformation was created by using human cytochrome P-450 3A4 expressed in Eschelichia coli and Saccharomyces cerevisiae. In the first experiment we have used human cytochrome P-450 3A4 from Escherichia coli (isolated on NTA-column). In the second experiment microsomes isolated from Saccharomyces cerevisiae containing coexpressed human CYP 3A4, human CYP-reductase and human cytochrome b5 were used. The reactions were monitored by HPLC and MS. PMID- 17357590 TI - The influence of simvastatin at high dose and diltiazem on myocardium in rabbits, the biochemical study. AB - 3-Hydroxy-3-methyl-glytaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") have been proved to be extremely useful in the management of hypercholesterolemia, as well as in prevention of primary and secondary coronary heart disease. However, they may produce rare but severe muscle-related symptoms such as myopathy and rhabdomyolysis. Recent findings in vitro have shown that statins can reduce cardiomyocyte viability. The exact mechanism of statin myotoxicity still remains unclear. Diltiazem as CYP3A4 inhibitor, is a well recognized risk factor of skeletal muscles myopathy, if co-administered with simvastatin. It is not known whether such interaction affects myocardial efficiency causing biochemical changes. The experiments were performed on thirty six New Zealand white rabbits. The animals were divided into four groups receiving: 0.2% MC (control group): diltiazem (5 mg/kg); simvastatin (50 mg/kg) or diltiazem + simvastatin, daily for 14 days (po). The following biochemical parameters were estimated: creatine kinase (CK), serum transaminases (ALT and AST), as well as myocardial injury markers: troponin I (Tnl) and creatine kinase MB (CK-MB). Simultaneous administration of simvastatin and diltiazem caused 23 fold increase (p < 0.01), in rabbit serum CK levels and 20-fold increase (p = 0.056) in TnI levels, as compared to the initial values. Also in these rabbits significant increase in CK (12411,60 vs 839.87 IU/L) and TnI (0,26 vs 0,014 ng/mL), as compared to control group were observed. Significant increase in CK (12411,60 vs 1100,92 IU/L) and TnI (0,26 vs 0,012 ng/mL), as compared to diltiazem alone were noted, too. This may suggest another mechanism of drug-drug interaction than the one based on CYP3A4 inhibition if the impact on cardiac or skeletal muscle is considered. PMID- 17357591 TI - Determination of impurities in pharmaceutical preparations containing folic acid. AB - In the presented study, the HPLC method was used for the determination of impurities (p-aminobenzoic acid and p-aminobenzoyl-L-glutamic acid) in single component pharmaceutical products containing folic acid. The determination was performed using a spectrophotometric detector at lambda = 269 nm wavelength. PMID- 17357592 TI - Drug-related hospital admissions--an overview of frequency and clinical presentation. AB - Adverse drug reactions (ADR) are the cause of hospital admissions for millions of patients every year and are believed to be a major problem in terms of morbidity and hospital expenses. ADR are characterized by exceptional variety, both considering pathomechanism and clinical symptoms. During the time period between 2000-2004 at the Department of Dermatology a project was undertaken to monitor patients who were hospitalized as a result of ADR. Within five years 57 patients, including 30 men and 27 women were observed. The majority of the patients developed maculaopapular rash (16), urticaria medicamentosa and Quincke's edema (16) and erythema multiforme (15). The other cases included erythroderma (5), anaphylactic shock (2), lichenoid exanthem (1), bullous eruption (1) and Hoigne's syndrome (1). The most probable factors producing these changes were concluded to be non-steroid antiinflammation drugs (33%), antibiotics (7%) and other drugs from different pharmacological and chemical groups (carbamazepine, diltiazem, hydrocortisone, methotrexate and herbs). The frequency of occurrence of skin changes of particular type in age groups were also analyzed. The greatest number of skin changes in response to drug therapy was in the age group 41 - 60, while for the age group > 60 ADR revealed the greatest diversity in the clinical picture. The most probable explanation of these findings are the polypragmasy applied in the elderly patients and interdrug interaction as well as decreased efficiency of the organic clearances. PMID- 17357593 TI - Optimization of chiral separation of pramipexole on various polisaccharide stationary phases. PMID- 17357594 TI - Identification and determination of angiotensin II receptor antagonists with densitometric method. PMID- 17357595 TI - Determination by chromatographic methods of selected medicines reducing the level of cholesterol. PMID- 17357596 TI - Fluorimetric detection of aldehyde dehydrogenase activity in human saliva in diagnostic of cancers of oral cavity. PMID- 17357597 TI - Determination of oxytetracycline in biological matrix. PMID- 17357598 TI - Simultaneous determination of midazolam and its alpha-hydroxy metabolite in human plasma by LC-MS using an automatic solid-phase extraction system. PMID- 17357599 TI - Validation of analytical procedure--control of residual ethanol, 2-propanol and ethyl acetate in pharmaceutical substance--imatinib. PMID- 17357600 TI - Validated LC-MS method for determination of tamsulosin in human plasma and its application to pharmacokinetic study. PMID- 17357601 TI - Investigations on the synthesis and properties of 2-(alkyl, aryl)-1,4,5-trioxo 1,2,3,4,5,6-hexahydropyrido[3,4-d]pyridazines, derivatives with potential biological activity. PMID- 17357602 TI - Synthesis of 1-aminomethyl derivatives of 3-benzyl-4-ethyl- 1,2,4-triazoline-5 thione. PMID- 17357603 TI - Synthesis of some n-substituted derivatives of 1-(1h-pyrrole-1 -ylmethyl)- 10-oxa 4-azatricyclo [5.2.1.0(2,6)]dec-8-ene-3,5-dione with an expected anxiolytic activity. PMID- 17357604 TI - An approach to enantioselective activation of N-benzoyl-alpha-methylserine with chiral N-triazinylammonium chloride. PMID- 17357605 TI - Unnatural D-amino acids as building blocks of new peptidomimetics. PMID- 17357606 TI - Synthesis and antiproliferation activity of the products obtained in the reaction of N3-substituted amidrazones from 1,2-cyclohexanedicarboxylic anhydride. PMID- 17357607 TI - Clustering as a supporting tool for structural drug design. PMID- 17357608 TI - Simvastatin intensifies heart rate depression after metoprolol and atropine administration in normocholesterolemic rats. PMID- 17357609 TI - Influence of sodium butyrate on antioxidative enzymes activity in Caco-2 cell lines. PMID- 17357610 TI - Anti-proliferative effects of inositol hexaphosphate and verapamil on human colon cancer Caco-2 and HT-29 cells. PMID- 17357611 TI - Antoxid increases ferric reducing antioxidant power (FRAP) even stronger than vitamin C. PMID- 17357612 TI - The influence of antoxid on chemically induced lipid peroxidation. PMID- 17357613 TI - The incidence of jaw osteonecrosis in multiple myeloma patients treated with bisphosphonates. PMID- 17357614 TI - The efficacy and safety of bortezomib (velcade) in the treatment of relapsed multiple mye. PMID- 17357615 TI - Growth of human chondrocytes on biodegradable synthetic polymers. PMID- 17357616 TI - Estimation of antimicrobial activity of selected non-antibiotic products. PMID- 17357617 TI - Antimicrobial activities of 4-substituted-3-(piperidin-4-yl)-4,5-dihydro-1H-1,2,4 triazole-5-thiones. PMID- 17357618 TI - Submerged cultivation of Streptomyces tsukubaensis in media composed of waste products of food industry. PMID- 17357619 TI - Molecular properties of econazole and sulconazole relevant to bioavailability. PMID- 17357620 TI - [Cell biology researches aboard the robotic space vehicles: preparation and performance]. AB - The article reviews the unique aspects of preparation and performance of cell biology experiments flown on robotic space vehicles Bion and Foton, and gives an overview of key findings in researches made under the author's leadership over the past decades. Described are the criteria of selecting test objects, and the conditions required for preparation and implementation of space and control (synchronous) experiments. The present-day status and issues of researches into cell responsivity to space microgravity and other factors are discussed. Also, potentialities of equipment designed to conduct experiments with cell cultures in vitro and populations of single-celled organisms are presented, as well as some ideas for new devices and systems. Unveiled are some circumstances inherent to the development and performance of space experiments, setting up laboratory facilities at the launch and landing site, and methods of safe transportation and storage of biosamples. In conclusion, the author puts forward his view on biospecies, equipment and areas of research aboard future space vehicles. PMID- 17357621 TI - [Medium-term forecast of solar cosmic rays radiation risk during a manned Mars mission]. AB - Medium-term forecasting radiation hazard from solar cosmic rays will be vital in a manned Mars mission. Modern methods of space physics lack acceptable reliability in medium-term forecasting the SCR onset and parameters. The proposed estimation of average radiation risk from SCR during the manned Mars mission is made with the use of existing SCR fluence and spectrum models and correlation of solar particle event frequency with predicted Wolf number. Radiation risk is considered an additional death probability from acute radiation reactions (ergonomic component) or acute radial disease in flight. The algorithm for radiation risk calculation is described and resulted risk levels for various periods of the 23-th solar cycle are presented. Applicability of this method to advance forecasting and possible improvements are being investigated. Recommendations to the crew based on risk estimation are exemplified. PMID- 17357622 TI - [Some results of radiaton monitoring of the ISS Russian Segment in 2000-2005]. AB - Dynamics of the ISS RS radiation environment was studied using the data of daily (operative) monitoring and personal dose measurements during 11 increments in the period between August 1, 2000 and October 28, 2005 overlapping the maximum phase of the 23rd solar cycle. It was shown that personal absorbed doses varied within the range of measurements of dual wavelength radiometer R-16, a component of the ISS radiation monitoring system. Power of the absorbed doses fell in the range of 0.017 to 0.02 cGy/day and was solar-dependent. PMID- 17357623 TI - [Dependence of mice fibrobslasts radiosensitivity on the exposure conditions]. AB - In the scientific literature there is lengthy discussion concerning utilization of low-dose hypersensitivity and bystander in radiation therapy which inspired us to investigate these effects using cells of mice fibroblasts C3H10T1/2. Irradiated were monolayers of fibroblasts cells cultivated on wall of plastic vials. To study the bystander effect, the therapeutic proton beam with the onset energy of 150 Me V was directed at the whole wall (25 cr2) or only the central area of 1 cv(2). In an hour after irradiation the cells were dispersed in 0.25 % tripsin solution and inoculated in vials for survivability analysis. In both cases survivability of the cells was essentially equal following irradiation by 0.5 Gy, 2 Gy and 5 Gy. The same observation was made also after fractionated irradiation by the total doses of 10 and 20 Gy (2 Gy per a day, 5 times a week). In these experiments, each time another area (1 cm(2)) of the vial wall was subjected to irradiation. Three 0.4 Gy fractionated irradiations of cells C3H10OT1/2 per a day (5 times a week) by gamma-source 60Co with an interval of 3 hours showed that the total dose of 6 Gy and 12 Gy gathered by this protocol had the strongest lethal effect on fibroblast cells as compared with the daily one time irradiation by 1.2 Gy. According to these results, detail studies of the low dose hypersensitivity and bystander effects may come up with their effective utilization in radiation therapy. PMID- 17357624 TI - Compliance changes in femoral veins of rabbits after 21 days of simulated weightlessness. AB - Increased venous compliance in lower limbs may be contributed to postflight orthostatic intolerance; however, direct animal studies to address the changes of venous compliance to microgravity have been rare. The purpose of this study was to determine compliance changes in femoral veins of rabbits after 21 days of head down rest. Head-down rest -20 dgrees rabbit model was used to simulate weightlessness. 24 healthy male New Zealand Rabbits were randomly divided into 21 days of head-down rest group (HDR), horizontal immobilization group (HIG) and Ctrl group (Ctrl), with 8 in each. We constructed pressure-volume relationships from femoral veins in vivo for all groups after simulation by changing the venous internal volume and measuring the corresponding pressure. Microstructure of femoral vein wall in 3 groups was observed. Compared among the groups, the corresponding intravenous pressure of Ctrl was the highest when intravenous volume was expanded and HDR was the lowest. The parameter 3 , and P 2 in quadratic equations of femoral venous P-V relationship of HDR group were significantly higher than these values of HIG group and Ctrl group. The structure of femoral vein wall of HDR rabbits changed significantly, outlines of some endothelium cells (EC) became short and columnar or cubic, some of EC fell off and smooth muscle layer became thinner. These results indicate that, the femoral venous compliance increased after weightlessness simulation. This may partially underlie the mechanism of orthostatic hypotension seen in astronauts during an orthostatic stress after exposure to microgravity. PMID- 17357625 TI - [Studies of the primary effects of chronic clinostatting of embryonal mice stem cells in vitro]. AB - Effects of randomized gravity vector (clinostatting) on embryonal stem cells (ESC) of mice were evaluated in vitro with respect to proliferation, proliferative potential, and differentiability. Colony formation remained normal up to hour 72 of clinostatting; however, further exposure led to fusion of the ESC colonies. No reliable shifts in the proliferative activity were found, whereas morphometric analysis showed different dynamics of the ESC colonies size in specific periods of the experiment comparing with the control. Evaluation of the ESC proliferative potential after the experiment revealed a trend upward in the number of colonies when compared with the dynamic and static controls. However, the number of resulted EBs in the control tended upward contrary to EBs formed under the conditions of clinostatting and continuous agitation pointing to the importance of local medium conditioning at the beginning of ESC differentiation. PMID- 17357626 TI - [Fractionation of hydrogen stable isotopes in the human body]. AB - Fractionation of hydrogen stable isotopes was studied in 9 human subjects in a chamber with normal air pressure imitating a space cabin. Mass-spectrometry of isotopes in blood, urine, saliva, and potable water evidenced increases in the contents of heavy H isotope (deuterium) in the body liquids as compared with water. These results support one of the theories according to which the human organism eliminates heavy stable isotopes of biogenous chemical elements. PMID- 17357627 TI - [Cytogenetic impacts of air-argon environment on epitheliocytes of the mice cornea]. AB - The purpose was to look into the effects of 24-hr. exposure in a normoxic air argon environment (AAE) on the epitheliocyte proliferative system, i.e. chromosomal aberrations dynamics and cornea proliferative activity, in laboratory mice. Argon was found to significantly decrease the percentage of spontaneous mutations in cells and, probably, to induce reversible inhibition of cell division. Subsequent experiments may not only disclose the still unknown properties and advantages of argon but also shed light on cell mechanisms triggered by the noble gases in general. PMID- 17357628 TI - [Parametric control of the yield characteristics and species composition dynamics of algal poly-culture]. AB - There are several experimental models of biological life support systems (BLSS) designed to incorporate a chlorella pool. These BLSS can be optimized if populated by algal associations that could take up more functions within the closed cycling system than a single alga species. Introduction of a Spirulina and Chlamydomonas poly-culture with differing in gas exchange and biochemical composition resulted in a tighter closure of linkages within the system. The factors determining the size of a species population in intensive continuous poly cultures are, first and foremost, pH and suspension flow rate. Experimental testing of this supposition brought us to the conclusion that parametric control of alga productivity and species composition dynamics makes it possible to create a steady intensive poly-culture as part of the LSS for humans. Flow rate and pH can be the parameters for control of the Spirulina and Chlamydomonas populations during continuous cultivation of this poly-culture. PMID- 17357629 TI - [Personality and psychic deadaptation of airline pilots with neurocirculatory dystonia]. AB - In-depth clinical psychological investigation of airline pilots with neurocirculatory dystonia (n=194, mean age 38.57 +/- 0.85) and essentially healthy control pilots (n=183, mean age 38.4+/-0.92) revealed distinctive features in NCD pilots' mentality and behavior including personality, interpersonal communication, type of thinking, stress reaction, protection tactics, and mental dysfunctions. Psychic deadaptation such as symptoms of psychic asthenia, paranoia, depression, schizophrenia, and impulsive behavior had a negative effect on the clinical course and led to medical disqualification of 15% of NCD pilots. PMID- 17357631 TI - [Development of an automated microbiological analyzer]. AB - An automated hematological analyzer, prototype of a quick microbiological diagnostics system, was tested positively for the ability to differentiate microbial cells (six test-strains with different morphological and tinctorial properties) by geometry and dye intensity. PMID- 17357630 TI - [Topical electrophysiological correlates of emotional states (on the evidence of incipient hypertension encephalopathology)]. AB - Comprehensive investigations of 97 patients with incipient hypertension encephalopathologies were performed with the use of standard psychodiagnostic questionnaires and EEG. Topographic analysis of spectral power showed stable constellation of altered alpha- and beta-zones in the EEG parietal, temporal and occipital leads. Given the clinical implications of this finding, we can view it as a potential neurophysiological background for depression, and a "functional" phase in disease development. PMID- 17357632 TI - [Procedure of blood agregation system analysis]. AB - Blood aggregation system analysis may become an effective tool for flyers health evaluation. Experimental or clinical laboratory parameters of blood coagulation and viscosity are used in the BA integral equation permitting qualitative and quantitative assessment of three biological forms of the coagulation and viscosity potential, and biochemical and biophysical protection potential. The method features accurate diagnostics of the body functions and choice of adequate treatment of BA disorders caused by dysfunctional viscera and tissues. PMID- 17357633 TI - [Effects of mechanic stimulation of the foot support zones on locomotion kinematics during 7-day dry immersion]. AB - The dry immersion experiment involved two groups of test volunteers. In one group, the volunteers were subjected to nothing else but immersion; in the other, foot support zones of the immersed volunteers were given daily mechanic stimulation. Evaluated were kinematics of normal locomotion during a series of test walks along rigid surface at a rate of 90 steps per a minute. The results of testing brought to the conclusion that the rates of mechanic foot stimulation applied in the experiment did not change energy expenditure in the joints; however, they moderated the amplitude of angular knee joint movements following 7 days in immersion. PMID- 17357634 TI - Onychomycosis in eastern Nepal. AB - Onychomycosis, a fungal infection of the nail is responsible for up to 50.0% of all nail diseases. Though, dermatophytes are most frequently implicated as the causative agents in onychomycosis, yeast and molds are increasingly recognized as causative pathogens. This study was aimed to know the clinical and mycological pattern of onychomycosis in eastern Nepal. Eighty-two clinically diagnosed patients of onychomycosis attending the Dermatology Outpatient department of a tertiary hospital over a period of one year were enrolled in this study. Clipping from the severely affected nail and skin scrapping from active border of the skin lesions if associated were collected from each patient and subjected to microscopy and culture for identification of fungi. The commonest affected age group was 21-40 years. The male: female ratio was 2.7:1. Fifty-one patients had isolated fingernail involvement, while involvement of toenails was seen in 15 patients. Distolateral subungual onychomycosis (67%) was the commonest clinical type followed in decreasing order by superficial white onychomycosis (14.6%), proximal subungual onychomycosis (9.8%), candidal onychomycosis (7.4%) and total dystrophic onychomycosis (1.2%). Trichophyton mentagrophytes (28.8%) was the most common pathogen isolated followed by Trichophyton rubrum (21.2%), Trichophyton tonsurans (11.5%), Candida albicans (11.5%), Trichospron beigelii, (9.6%), Epidermophyton floccosum (7.7%), Trichophyton violaceum (5.8%), and Aspergillus flavus (3.9%). Distolateral subungual onychomycosis was the most common clinical presentation and T. mentagrophytes and T. rubruni were the most frequently isolated fungi for onychomycosis in eastern Nepal. PMID- 17357635 TI - Study of depression among geriatric population in Nepal. AB - Depression is one of the commonest psychiatric disorders among the elderly patients attending the outpatient department of the tertiary care hospital. The consequence of unrecognized and untreated depression in the elderly population may include excessive use of health care services, decreased treatment compliance and increased morbidity and mortality related to underlying medical illness and from suicide. The aim of the study is to estimate the prevalence of depression according to Geriatric Depression Scale (GDS) and to find out the association of GDS with ICD-10 Diagnostic Criteria for Research (ICD-10 DCR) among older adults in the Nepalese population. A study group of 100 elderly patients aged 65 years and above were randomly selected from the psychiatry, medicine and general practice outpatient departments of Tribhuvan University Teaching Hospital, Nepal. MMSE scale is administered and the patients scoring more then 24 were administered the GDS and clinical diagnosis was made according to ICD-10 DCR. 53.2% of the samples were found to experience depressive illness according to GDS which includes 34.2% of mild and 19% of severe depression. 83.3% of the patients diagnose with probable depression with GDS were also diagnose clinically with ICD 10 DCR (p<0.001). This study concludes that significant number of elderly patients attending OPD of tertiary care hospital suffers from depression and GDS is a reliable tool to screen depression in the Nepalese patients. PMID- 17357636 TI - Effect of phosphamidon on the testes of albino rats: a histological study. AB - The present study shows the qualitative and quantitative histological changes in testes of albino rats treated with two doses of phosphamidon 35 and 50 parts per million(ppm) for 1 month time period. Rats were treated by drinking water containing 35 ppm (low dose) and 50ppm (high dose) concentration of phosphamidon for 30 days. After 30 days, they were sacrificed, the testes were fixed in vivo and were taken out. The histological slides of these testes were prepared and were studied under light microscope. The decrease in the weight of testes and diameter of seminiferous tubules, increase in the interstitial space, the decrease in the numbers of germ cells and supporting cells, Cytoplasmic vacuolization of the germ cells, distortion of seminiferous tubules were the findings of present study. phosphamidon seems to be toxic on male reproductive system if exposed for prolong period. The awareness regarding the impact of phosphamidon should be given to farmer and they should be encouraged to practice biological means to control pests and herbs instead of these harmful chemical compounds. PMID- 17357637 TI - Effect of tension on force of contraction of muscle and nerve conduction velocity of the repaired nerve in a rat model. AB - To investigate the effect of tension on the contractive force of muscle and nerve conduction velocity of the repaired nerve, this study was designed. Fifty-four Sprague-Dawley (SD) rats were randomly divided into 3 groups. The left gastrocnemius muscles of the rats were dissected with the neurovascular pedicles intact; the tibial nerves were cut and immediately repaired by epineurial suture. Then the Achilles tendons were isolated and treated accordingly; the Achilles tendon was lengthened by 0.5 cm in lengthened group, shortened by 0.5 cm in shortened group and left alone in normal (control) group. In the 2nd, 4th and 8th weeks after operation, the isometric twitch contractive force of both the right and the left gastrocnemius muscles and the nerve conduction velocity (NCV) of the tibial nerve were measured. The shortened group showed greater isometric twitch contractive strength of the bilateral gastrocnemius muscles than those in the normal and lengthened groups in all the postoperative periods. The nerve conduction velocity (NCV) in the shortened group showed greater than other groups. A proper high tension of the muscle can increase the contraction of the muscle and may improve the nerve conduction velocity of the repaired nerve. PMID- 17357638 TI - Outcome of Lichtenstein operation: a prospective evaluation of sixty-four patients. AB - To assess the feasibility and safety of open tension-free mesh repair (Lichtenstein operation) of inguinal hernias on ambulatory surgery basis. A prospective study of the Lichtenstein operation on 64 patients of inguinal hernias who were operated the authors and surgical trainees at Unit III, Department of General Surgery at National Academy of Medical Sciences (NAMS), Nepal from April 13, 2004 to April 31, 2006. Data related to age, sex, characteristics of the hernia, feasibility of the Lichtenstein operation under unmonitored local anesthesia and its surgical outcomes were compiled prospectively. The inguinal hernia was virtually a disease of male patients. In this study, male: female ratio was 63:1. Majority (84.4 %) of the inguinal hernias were safely operated under local infiltration anesthesia on day surgery basis with minimal morbidity rate (14.0%). The inguinal hernia is one of the common surgical problems of the adult population. The Lichtenstein operation can be safely performed on ambulatory surgery under unmonitored local anesthesia with a low morbidity. Hence, local anesthesia technique for the hernia repair is a viable alternative to spinal or general anesthesia. PMID- 17357639 TI - Student's critical appraisal on the evaluation of analgesics in laboratory animal verses simulated clinical trail. AB - Effective feedback is an integral part of medical education in helping the medical students to reach their maximum potential. Without feedback mistakes may go uncorrected which results poor performances of learners as well as tutors. At present teaching learning methodology used in many medical colleges includes lectures, tutorials, practical and occasionally small groups teaching and case discussions. The curriculum of undergraduate medical and dental students of BP Koirala Institute of Health Sciences, Dharan, Nepal is need based, integrated, co mmunity oriented, partially problem based. The practical lessons are an important part of Pharmacology curricula of undergraduate courses. So the aim of this study was to evaluate the student opinion towards animal experimentation as well as simulated clinical trial (SCT) on analgesics in terms of understanding the objectives. To conduct the study a semistructure questionnaire were provided to 2nd years MBBS and BDS students to obtain their view. Of the 164 questionnaires 154 students submitted completed questionnaire. On analysis of the feedback, it was observed that 77.9% students liked animal experiments and most of them wee happy with simulated clinical trial. The majority of the students 74.1% favoured both exercises for improved understanding of the subject and 66.2% agreed the sequential sessions. So the study concludes with the view that sequential sessions of laboratory experiments as well as SCT are required for a rectified learning of Pharmacology. PMID- 17357640 TI - A profile of ectopic pregnancy at nepal medical college teaching hospital. AB - A retrospective study of ectopic pregnancy at Nepal Medical College Teaching Hospital between January 2001 to June 2006 was carried out to determine incidence, demographic features, clinical presentation, duration at presentation and treatment, and the management protocol. A total of 36 cases of ectopic pregnancy were treated giving the incidence of ectopic pregnancy of 10.2/1000 deliveries and 7.3 /1000 pregnancies. The mean age is 30.1 years (range 23-45 years) and the mean parity is 1.2 with nulliparous at 49%. The mean gestational age is 6.9 weeks (range 5-11 weeks). Among the ethnicity, Mongolians constituted at 54.6%. The commonest risk factors present were infertility (33.3%), previous ectopic pregnancy (16.7%), pelvic inflammatory disease (13.9%) and tubal surgery (13.9%). The commonest symptoms at presentation are abdominal pain (94.4%), amenorrhea (72.2%) and abnormal vaginal bleeding (58.3%); and commonest signs were abdominal tenderness (91.7%), adnexal tenderness (72.2%) and cervical excitation (50.0%). The mean time from symptom to treatment was 176.58 hours and mean time from admission to treatment was 12.88 hours. Ectopic pregnancy was correctly diagnosed clinically in 85.0% patients including 42.5% (12/36) of ruptured ectopic pregnancy. Abdominal ultrasound and urinary a-hCG tests (ELISA test) were additional diagnostic tools. Sixty one percent (22/36) presented in subacute condition. Two cases (5.6%) were presented late causing diagnostic problem and more morbidity like anaemia, blood transfusion, adhesion needing major operations. Salpingectomy is the mainstay of treatment. Only one case has conservative surgery. Late presentation and ruptured ectopic pregnancy is associated with increased morbidity and mortality. High index of suspicion and early recourse to laparotomy save the life from this obstetric disaster. PMID- 17357641 TI - Intestinal parasitosis among the elderly people in Kathmandu Valley. AB - Present study was carried out among the elderly people (60+ years of age) from August 2005 to July 2006 in Kathmandu Valley to assess the prevalence of intestinal parasitosis in them. Stool samples were collected from 235 elderly people (122 from government elderly home, 66 from private elderly home and 47 from the households in a rural community). The samples were examined by formal ether sedimentation and Sheather's sucrose floatation followed by Kinyoun's modified Ziehl-Neelsen staining. The overall prevalence of intestinal parasites was found to be 41.7%, out of which 30.6% had multiple parasitism. The government elderly home had significantly higher parasitic prevalence (50.8%) followed by the rural community (46.8%) and the private elderly homes (21.2%) (P<0.05). Males (43.8%) had slightly infection rate than females (40.4%) (P>0.05). There was equal infection rate with protozoa (25.8%) and helminths (27.0%). Trichuris trichiura (39.4%) and Entamoeba histolytica (19.7%) were the commonest helminth and protozoa, respectively. PMID- 17357642 TI - Trend of blood group distribution among the different ethnic groups of Kathmandu Valley. AB - This study was undertaken to find out the trend of blood group distribution (ABO and Rh) among the 1310 Nepalese attended in Tribhuvan University Teaching Hospital and Nepal Medical College Teaching Hospital Kathmandu. The frequency of distribution of A, B, AB and O was 28.5%, 27.3%, 8.7% and 35.5% respectively. Only 0.8% of them were found to be Rh (-) ve. In this population of study, O (+) ve blood group was found to be predominant among the Brahmins, Magars and Gurungs. A (+) ve blood group was predominant among the Chhetris, and B (+) ve among the Sherpas and the Lamas. PMID- 17357643 TI - Assessment of proteinuria as a marker of nephropathy in type 2 diabetes mellitus. AB - This is a cross sectional hospital based study carried out at Om Hospital and Research Center Kathmandu, Nepal. In the study, 200 diabetic patients attending the hospital were taken as the subjects and we evaluated the urinary albumin excretion and other biochemical parameters (such as creatinine, total cholesterol, HDL cholesterol, LDL cholesterol), blood pressure and body mass index (BMI). Among these 200 patients with type 2 diabetes mellitus (DM), 52.0% were having high blood pressure. The proteinuria was present in 23.0% of the overall subjects but when it is categorized in hypertensive and non-hypertensive group, 30.7% of the diabetic patients with hypertension were having proteinuria. It has been found that males were having higher prevalence ofproteinuria (53.8%) than female (17.6%). There was significant difference in systolic blood pressure, diastolic blood pressure in nephropathy and without nephropathy group. Thus the nephropathy or the incidence of proteinuria was associated with obesity, high diastolic blood pressure and male sex. These data suggest that control of diabetes; hypertension should decrease the risk for proteinuria thus decreasing end stage renal disease (ESRD) and mortality from ESRD. PMID- 17357644 TI - Sonographic morphological features of ovarian tumours. AB - Fourty five patients with ovarian tumours were studied for their sonographic morphological characteristics and were followed up with histopathological report for correlation between most important sonographic features of benign and malignant ovarian tumours. Among different features, thin wall, smooth inner wall structure and anechogenicity or low echogenicity of the lesions were more important features of benign tumours. Complex mass without demonstrable wall, indistinct inner wall structure and highly echogenic lesion with solid component were predictors of malignancy. PMID- 17357645 TI - Vaginal hysterectomy vs abdominal hysterectomy. AB - This was a prospective study, conducted to analyze the intraoperative complications, postoperative morbidities and complications between abdominal and vaginal hysterectomy. This study was carried out on 100 patients (50 cases abdominal and 50 cases vaginal hysterectomy), in Services Hospital, Lahore in the year 2002 from April to December. Among the intraoperative observation, the mean duration of surgery of abdominal hysterectomy was 96.8 min and that of vaginal was 89 min (p=0.0192). The mean blood loss in abdominal hysterectomy was 311 ml and that in vaginal hysterectomy was 244ml (p=0.0017). Postoperatively febrile morbidity was seen in 10 (20.0%) cases of abdominal hysterectomy group and 6 (12.0%) of vaginal hysterectomy group. Wound infection was the main cause for febrile morbidity in abdominal hysterectomy group where as urinary tract infection was the main cause for febrile morbidity in vaginal hysterectomy. There was one case of bladder injury and 1 case of ureteric injury in abdominal hysterectomy group while none in vaginal hysterectomy group. There were 2 (4.0%) cases of postoperative haemorrhage in abdominal hysterectomy group and none in vaginal hysterectomy group. Vault infection occurred in 2 (4.0%) cases of both the groups. Two (4.0%) cases of paralytic ileus, 2 (4.0%) cases of chest infection and 1 (2.0%) case of rectal muscle hematoma were seen in abdominal hysterectomy group. Overall 39 (78.0%) cases of abdominal hysterectomy and 1 (32.0%) case of vaginal hysterectomy had complications (p=0.0002). This study showed that vaginal hysterectomy was associated with less intraoperative complications and postoperative morbidities and complications as compared to abdominal hysterectomy. PMID- 17357646 TI - Spectrum of stones composition: a chemical analysis of renal stones of patients visiting NMCTH. AB - A general observation of clinicians suggests that the prevalence ofurolithiasis is fairly high in Kathmandu but so far no systematic study has been undertaken here to explore the etiopathogenesis of disease in this region. In this preliminary communication, we present herewith the qualitative composition of 47 renal stones collected from surgical patients admitted to NMCTH over a period of 13 months (July 2005 to July 2006). All stones were of mixed type. Calcium was present in all stones. Oxalate, phosphate and uric acid were present in 95.7%, 87.2% and 34.0% patients respectively. The probable composition, as construed from analysis, suggests that calcium oxalate stones are predominant. Strikingly, the prevalence was very high in e"20 yrs age group. PMID- 17357647 TI - Seasonal variation of skin diseases in Nepal: a hospital based annual study of out-patient visits. AB - The aim of this study was to determine whether there was seasonal variation in skin diseases amongst dermatology out-patients in Nepal. A retrospective study was done of all new out-patients visiting a single dermatologist, at the Om Hospital and Research Center, Kathmandu, Nepal. The study population comprised all new patients visiting the dermatology out-patient department, between January and December, 1999. Data were obtained from the hospital out-patient records and analyzed. The total number of patients with skin diseases was 1746 (Males-793; Females-953). Majority (28.6%) of the visits was in spring and the three most common diagnoses included fungal infections, acne and melasma. All skin diseases showed statistically significant seasonal variation. It is clear that occurrence of certain skin diseases in Nepal show a significant seasonal trend. PMID- 17357648 TI - Retrospective analysis of stroke and its risk factors at Nepal Medical College Teaching Hospital. AB - Stroke is a major public health burden worldwide and is responsible for a large proportion of disability; and ranks third in the causation of morbidity and mortality. This disease although regarded as a disease of old age, it is not uncommon in younger population in developing countries.. A retrospective study of cerebro-vascular accidents (stroke) managed at Department of Medicine, Nepal Medical College Teaching Hospital during the period of 1st April 2000 to 31st March 2005 was done to study demographics and risk factors. Cases of TIA were not included in the final analysis of the data due to uncertainty of diagnosis and lack of imaging (CT scan). The collected data was analyzed using data analysis software SPSS (version 12). We identified 72 cases of stroke excluding TIA. The mean age at which patients in this study experienced their first ever stroke was 61.7 yrs (SD 14.9 yrs). The commonest presenting complaints in our study population were weakness of limbs (90.3%), slurring of speech (33.3%), altered mental status (29.8%), deviation of angle of mouth and headache (22.2%) each and urinary incontinence (13.9%). Vomiting, dizziness, fever, personality changes, seizure, tingling sensation of limbs were uncommon clinical presentation and were present in 15.28% of cases. Risk factors were smoking (58.3%), hypertension (47.2%), alcohol (41.4%), atrial fibrillation (12.5%) and diabetes mellitus (11.1%). To conclude, stroke in countries like Nepal is a public health problem. The clinical presentations and risk factors are in agreement with other studies. The low mean age of stroke patient reflects demographic feature of this region. PMID- 17357649 TI - Analytical study of the management of supracondylar fracture of children in our setup. AB - We performed a clinical-radiological audit of 142 children with consecutive upracondylar fractures of the humerus over a period of 5 years (1996-2001). The fractures were classified according to the Gartland system; 58 types I, 44 type II and 40 type III. And 87.0% were extension and 13.0% flexion types. These cases were managed by closed reduction and posterior cast application (n= 120) and open reduction with internal fixation (n=22). All the stable fractures irrespectable of types were managed by closed method and all the unstable or failed manipulation cases were operated upon. In total 38 required re manipulation in the cast group and twelve (n= 12) had a varus deformity (ten from closed group and two from operation group). Failure to follow the treatment according to the guidelines led to an unsatisfactory result in 12 patients. We have devised a protocol for the management of these difficult injuries in our setup for optimal outcome. PMID- 17357650 TI - Visual status of Nepalese national football and cricket players. AB - This study was undertaken to assess the visual acuity, refractive status, stereopsis, colour vision and ocular morbidity of Nepalese national footballers and cricketers. Ninety-five national football and cricket players of different age group, who had at least played one international tournament representing Nepal, were included in the study. A thorough ocular examination of the players was done in the study period of six months, which revealed that higher-level professional players have significant visual problems. Among the players 70.0% had never had complete ocular examination, 8.0% were found with refractive error, 60.0% with stereo acuity equal or less than 40" of arc and 65.0% with ocular complaints. PMID- 17357651 TI - Unusual lateral presentation of popliteal cyst: a case report. AB - The commonest cyst to occur in the popliteal region is the popliteal cyst and over the past years it has received much clinical attention. The commonest position of the popliteal cyst is in the posterosuperior aspect of the medial femoral condyle. The present case report describes a rare case of popliteal cyst, which was found on the postero-superior aspect of the lateral condyle of the femur. Interestingly, there are fewer reports of popliteal cysts occurring in the postero-superior aspect of the lateral condyle. We as anatomists describe the topographical anatomy of an unusual presentation of popliteal cyst in the postero superior aspect of the lateral popliteal region and discuss its clinical significance. Anatomical knowledge of such anomalies may be important for clinicians, orthopedic surgeons and academicians in routine clinical practice. PMID- 17357652 TI - Unusual venous drainage of face: a case report. AB - Facial region has enormous blood supply. The maxillary vein, facial vein and superficial temporal vein are chief venous draining channels. There are numerous reports of unusual venous system of face, in the present case, retromandibular vein divides into anterior and posterior division soon after its formation, external carotid artery lying lateral to retromandibular vein, formation of common venous channel between internal jugular vein and anterior jugular vein where facial, lingual and submental vein drain. PMID- 17357653 TI - Ganglioneuroma of pelvis--an unique presentation in a young man. AB - Ganglioneuromas presented as a pelvic tumor around the pelvic organs is a rare entity. A case with unusual presentation is reported. Young man of 18 years old presented with a complaint of lower abdominal mass increasing in size for last 3 years. It was treated with partial resection for debulking purpose after the conformation during surgery with frozen section. Debulking surgery with preservation of organ functions is feasible in these slow growing tumors for better quality of life. PMID- 17357654 TI - Oncocytoma of maxillary sinus--a rare presentation. AB - A case of Oncocytoma of maxillary sinus in a 73 years old female is reported along with a brief review of literature. To the best of our knowledge this extremely rare tumor is the first of its kind reported in Nepal. Literature review has revealed only four such cases originating from maxillary sinus. PMID- 17357655 TI - [Neurovascular conflicts]. AB - Neuro-vascular conflict is a pathophysiologic phenomenon which is implicated in several cranial neuropathies. The most common are trigeminal neuralgia and hemifacial spasm. Spasmodic torticolis, glosopharyngeal neuralgia, disabling positional vertigo may be due to neural compression as well, but other pathologies such as neurogenic hypertension and limited cases of tinnitus, although rare, highly susceptible to the neurovascular conflict, should be taken into considerration. Current diagnostic approach comprises clinical and radiological evaluation. Along with thorough otoneurological examination, MRI scans are essential to diagnose the conflict. This provides information about the presence of neuro-vascular conflict and involved structures. The microvascular decompression (MVD) is a treatment of choice, based on the separation of offending vessel from the nerve. Those procedures are safe, with high rate success according to the literature ranging from 70-90%. Additionaly, in early 90. a new minimally invasive approach with use of rigid endoscopes were proposed. Those gave the possibility to reduce morbidity and improve results by providing wider insight into the operating field with smaller intraoperative injury. Authors present 9 patients diagnosed with neuro-vascular conflict in the ENT department in Poznan. Clinical findings comprised 5 cases of hemifacial spasm, 3 with unilateral tinnitus and 1 with trigeminal neuralgia. Due to variety of symptoms, it is proposed that specialized centers should be formed to diagnose and treat cranial nerves neuropathies. Team approach composed of neurologist, neurosurgeon, radiologist and otologist is essential in terms of good treatment results. Authors describe symptomatology, diagnosis and treatment options of neuro-vascular conflicts. PMID- 17357656 TI - [Local changes in the oral cavity in patients after operation of malignant tumours of the tongue and bottom of the oral cavity]. AB - This study is aimed an objective and subjective evaluation of local changes after operations of malignant tumours of the tongue and the bottom of the oral cavity. THE MATERIAL AND METHODS: we have examined 74 patients (70 men and 4 women) treated in Department of Otolaryngology of the University School of Medical Sciences in Poznan with recognized of malignant tumour of the tongue and floor of the mouth. On the base of subjective and objective ultrasound and x-ray examination with use of contrast and stereognostic test it was evaluated movability, alteration of articulation zones, regularity of swallowing acts, sense of taste and efficiency of stereognosion. In all of the patients we found orders in swallowing, speech and taste dependen on the kind of the operation. PMID- 17357657 TI - [Histological charakteristics of tongue and floor of the mouth neoplasms and their clinical prognostic value]. AB - INTRODUCTION: The number of histological classifications has been introduced to asses the squamous cell carcinoma in head and neck. The Jakobsson histological system employs 8 different morphological characteristics. Four of them concerning tumor cell population and another four describe relation to the adjacent tissues. MATERIAL AND METHODS: The material comprised tissue specimens from 80 patients with squamous cell carcinoma of the tongue and floor of the mouth who underwent the primary surgery. All the data concerning Jakobsson classification, histological differentiation G, TNM classification, and recurrence and survival rates were recorded and analyzed. RESULTS: Any significant correlation has been found between Jakobsson classification and histological differentiation. Nevertheless statistically significant correlation between Jakobsson classification and T of the tumor, nodal metastases and local and nodal relapse has been recorded. CONCLUSIONS: The Jakobsson classification constitute the important supplement of the routine histological assessment and may significantly contribute to the choice of therapy. PMID- 17357658 TI - [Palatine tonsils colonization with actinomyces species during chronic tonsillitis]. AB - The Actinomysec spp. are common saprophytic microorganisms which are found in the oral cavity, pharynx and palatine tonsils. The actinomycotic infections can be responsible for recurrent chronic tonsillitis. Data about presence of actinomycotic granules in tonsillar tissue and their influence clincal course are controversial in the available literarure sources. The presence study assesses the appearance of actinomycetes and the character of their invasivenes in the tonsillar tissue affilicted with chronic tonsillitis after tonsillectomy which were performed in Department of Otolaryngology Medical University of Lodz in 2005. The clinical manifestations and histopathological findings were retrospectively reviewed. Actinomycotic granules were presented in 21 cases. Most frequently in positive cases the granules were in crypts accompanied by accumulation of inflammatory mononuclear cells and bacteriae migration through the epithelium into the tonsillar tissue. There was no correlation between the clinical diagnosis and course and the presence of Actinomyces. Our results indicate that actinomycetes may play an active role in the etiology of chronic inflammatory of tonsillar tissue and the causative factor. PMID- 17357659 TI - [Diagnostic and treatment in nasal polyps of children treated in Wroclaw ENT department in the years 1991-2001]. AB - BACKGROUND: Nasal polyposis is not often observed in children and usually follows general chronic diseases or disorders of cilliary structure or function and occurs mostly after 10 years of age. This is why in children clinical changes qualified as nasal polyposis should always be verified as congenital diseases or neoplasmatic changes. CASE REPORT: The population: of children treated in the years 1991-2001 in the Wroclaw ENT Department with initial diagnosis of nasal polyposis was presented. Material consisted of 52 children admitted in the years of 1991-2001 to Wroclaw ENT Department with already diagnosed nasal polyposis. In each case medical history was collected together with routine physical ENT examination complemented with fiberoendoscopic examination of the nose end epipharynx. In 7 children with initial diagnosis of nasal polyposis hypertrophy of pharyngeal tonsil with vasomotor rhinitis was diagnosed. Those children underwent adenectomy. Remaining group of 45 children aged from 2 to 16 years was analysed. Surgical treatment (polypectomy, FESS) was performed in 44 children. There was antrochoanal polyp in 10 cases (20,4%), monolateral choanal atresy in 1 case, foreign body of nasal cavity in 1 case and neoplasmatic tumour diagnosed in 5 cases. CONCLUSIONS: The diagnostic difficulties in nasal polyposis in children, except neoplasm, are reflected by the cases with initial diagnosis of nasal polyp and finally diagnosed as foreign body with inflammatory reaction or monolateral choanal atresy. Endoscopic examination of nasal cavity together with radiological diagnostic should be ordered routinely in the unclear cases. PMID- 17357660 TI - [Benign paroxysmal positional vertigo in the own material]. AB - INTRODUCTION: The complaint of dizziness can be caused by a variety of disorders affecting central or peripheral vestibular system. Benign paroxysmal positional vertigo BPPV is the most common cause of vertigo. It is a syndrom characterized by short-lasted episodes of true vertigo, induced by a rapid head position change and associated with a positional, transient nystagmus. It is classically identified by the Dix-Hallpike test. Vestibular and audiology function tests are usually normal. Patient is succesfully treated with physical maneuvres (Canalith Repositioning Procedure CRP). MATERIAL AND METHODS: This raport presents eight patients (four are described in details) suffered from BPPV-PSC, hospitalized in the Department of Phoniatric and Audiology, Poznan University of Medical Sciences. Methods include laryngologic examination, audiology and vestibular tests, Dix-Hallpike'a maneuver. RESULTS: All patients presented characteristic history and results of performed diagnostic tests. The efficacy of physical maneuvers were confirmed. CONCLUSIONS: BPPV is usually easy to diagnose and physical maneuvers are very effective. PMID- 17357661 TI - [Successes and failures of ozena's medical treatment]. AB - Ozena belongs to the primary atrophic rhinitis of unknow etiology. The incidence of this disease has markedly decrease in the last decades. We treated 4 patients with ozena between 2000-2005. The diagnosis was confirmed by physical and ENT examination, culture from the nose and CT scan of perinasal sinusis. Ciprofloxacin was aministrated orally in a dose 1,0-0,5 g daily to all patients. Also they were instructed how to clean the nose regularly with an isotonic saline solution and to moisteurse nosa by wotery spray. The treatment with ciprofloxacin was maintained for 4-6 weeks. In 3 causes the result was very good after 2-4 y observation. 1 patient, 16 y. old girl, didn't cooperate therapy propely - she stoped nasal rinsing after some improvement. The second course of treatment seems to get good result (3 months observation). Our and some other authors conclusion is: ciprofloxacin seems to be a promising drug for the treatment of ozena. For good results cleanising the nose regularly is importent as well as antibiotic. PMID- 17357662 TI - [Olfactory neuroblastoma (esthesioneuroblastoma): etiopatogenesis, diagnosis, and treatment]. AB - INTRODUCTION: Esthesioneuroblastoma is a malignant tumour arising from the olfactory epithelium located in the upper part of the nasal cavities. Recent clinical and preclinical studies shed more light on etiopathogenesis, diagnosis, and treatment of this rare malignancy. MATERIAL AND METHODS: A systematic review of PubMed/Medline and available Polish literature. RESULTS: Molecular studies indicate basal progenitor cells of the olfactory epithelium as the origin of esthesioneuroblastoma. Tumour symptoms are related to its location and typically include: epistaxis, nasal obstruction, olfactory and ophtalmic disturbances as well as craniofacial pain. Esthesioneuroblastoma should be differentiated from embryonic rhabdomyosarcoma, Ewing's sarcoma, melanoma, lymphoma, and pericytoma. A combination of surgery and radiotherapy seems to be the optimum approach to treatment. More aggressive treatment regimens are promising but require further studies. CONCLUSIONS: Esthesioneuroblastoma is a rare malignant tumour arising from the olfactory epithelium. Early diagnosis and interdisciplinary approach to treatment is vital in the management of the tumour. PMID- 17357663 TI - [Chlamydia pneumoniae occurrence in children with adenoid vegetations]. AB - INTRODUCTION: In world literature there is a lack on informations about occurrence frequency of Chlamydia pneumoniae in swabs fromadenoid vegetations. Chlamydia spp. is a group of nontypical pathogenetic bacteria. Initially they were fought a cause of lower respiratory tract. Nowadays they are considered as a pathogenetic factor of upper respiratory tract infections. They can also cause persistant infection. MATERIAL AND METHODS: During 3,5 months at the end of winter and bigining of spring, 110 children qualified to adenotomy (53 girls and 57 boys) were examinated. The average of age carried out 6,11 years. RESULTS: the positive results of direct immunophluorescence test (IFA) of adenoid vegetations swabs were received in 29 children (26.4%). Received results demonstrate chronic infection with Chlamydia pneumoniae. Pneumonia or bronchitis was noted additionally at 3 children (2.7%) in this in one child pneumonia caused by C. pneumoniae was diagnosed, secretory otitis media was diagnosed in 5 children (4,5%), asthma in 3 patients (2,7%). Confirmed infection Chlamydia pneumoniae occurred earlier at 5 children (4.5%). CONCLUSION: Results of direct immunophluorescence test(IFA) of adenoid vegetations swabs do not correlate directly with levels of anty-C. pneumoniae antybodies in blood. But antybody level could be supplementary to clinical symptoms and and swab result or give us information about infection history in patient. PMID- 17357664 TI - [The analysis of incidence of adenoid hypertrophy in children hypersensitive to dust mites]. AB - The adenoidectomy is the most often made operation in small children but the reasons of adenoid hypertrophy are not completely explain. Some researches show that in part of children allergy can be a risk factor for adenoid hypertrophy. The main aim of this study was the analysis of adenoid hypertrophy in children with different allergic diseases. MATERIAL AND METHODS: Two separate groups of children were examined. The study group consisted of 436 children between 4 and 9 years old with allergic rhinitis and/or bronchial asthma and/or atopic dermatitis hypersensitive to house dust mites (interview, positive skin-prick test results). The control group consisted of 229 non-atopic children (negative interview and skin-prick tests) in the similar age. In the both groups we examined the incidence of adenoid hypertrophy and its dependence of the kind of allergic disease, age, sex, infections, results of skin-prick test and other sensitisation. RESULTS: The probability of adenoid hypertrophy was statistically more significant (logistic regression analysis) only in children from the study group with allergic rhinitis. There were no differences in adenoid hypertrophy incidence between children with other allergic diseases and the control group. The children from the study group with adenoid hypertrophy were more often hypersensitive to pollen and moulds allergens than the children without adenoid hypertrophy (chi square test). But there were no differences in the incidence of infection, age, sex and results of skin-prick tests. CONCLUSION: The result of our study suggests that the chance of adenoid hypertrophy in allergic children hypersensitive to dust mites is greater only in them with allergic rhinitis. PMID- 17357665 TI - [Expression of adhesion molecule CD28 on subpopulations of lymphocytes in hypertrophied adenoids in children with otitis media with effusion]. AB - INTRODUCTION: The expansion of an optimal immune response requires fully activated T lymphocytes. For complete activation several signals are needed. The first signal is an antigen dependent via the TCR receptor, and the second signal is a costimulatory that can be delivered by the CD28 molecule after binding to their ligands. Fully activated T lymphocytes are competent to deliver activation to B cells. We suppose that this way can be important for development of immune response in hypertrophied adenoid (AH) in children with otitis media with effusion (OME). The aim of this study was evaluation of the percentage and MFI (mean fluorescence intensity) of lymphocytes CD4+, CD8+, CD19+ with expression of superficial adhesive molecule CD28 in hypertrophied adenoids in children with otitis media with effusion. MATERIAL AND METHODS: 37 children with otitis media with effusion and 35 children with hypertrophied adenoids were tested. Children were also divided into two subgroups: young (below 5 years) and older children (above 5 years old). Expression of adhesion molecule CD28 on lymphocytes of adenoids tissue was estimated by flow cytometry method. RESULTS: This study showed significantly higher percentage of lymphocytes CD4+CD28+ in children with otitis media with effusion (OME 93,87%) than in comparative group with hypertrophied adenoids (AH 91,01%). Mean fluorescence intensity CD28 was higher on subpopulation lymphocytes CD4+ to children with OME (3,94) than AH (3,32). We did not find difference between OME and AH in percentages and MFI of subpopulations CD8+CD28+ and CD19+CD28+ lymphocytes. CONCLUSIONS: Adhesion molecule CD28 is very important for adenoidal lymphocytes activation and protection against apoptosa. Higher percentage of lymphocytes CD4 with expression CD28 confirms their participation in developing and forming of immunological response in otitis media with effusion. PMID- 17357666 TI - [What should we know about uvula doing uvulopalatoplasty]. AB - INTRODUCTION: Investigators have been interested in the structure and function of the uvula for centuries. Some of them emphasized its influence on the tone of voice, others its immunological role. Since the times of Hippocrates, people have been afraid of the uvula oedema, as it could lead to apnea and death. It was also suspected that upper airway diseases originated from the uvula. That's why excision of the uvula has been a common practice in folk medicine carried out as a ritual act in the North Africa and Middle East for many centuries up to now. Nowadays Evidence Based Medicine recommends uvulectomy as a part of surgical treatement in any form of sleep related obstructive breathing disorders. The aim of this study was to present the specific function of the uvula and draw the practical conclusions concerning uvulopalatopharyngoplasty. MATERIAL AND METHODS: Histological analysis of the uvula and soft palate samples obtained by UPPP from 37 adults suffering from moderate OSAS was performed. RESULTS: This investigation revealed that the uvula contained significantly more salivary glands with predominant serous type in comparison with the palatine arches tissue. Glandular follicles were composed of the pyramid-shaped epithelial cells lying on the basement membrane. Between these there were myoepithelial cells which pushed serous secretion to the excretory ducts. CONCLUSIONS: Histologically unique structure of the uvula, when compared with other parts of the soft palate, suggests that the uvula plays a very important role in moistening the oropharyngeal mucosa. Since the feeling of dryness in the throat is one of the most frequent complaints after UPPP, the modification of the standard operative technique in order to preserve the uvula, should be considered. PMID- 17357667 TI - [Age connected hearing disorders (presbyacusis) as a social problem]. AB - The data of World Health Organization anticipate very rapid growth of percentage participation of elderly people in the population on the whole world. In Poland, in the year 2005, the percentage of people in the "post productive" age (women over 60 years, men over 65 years) was 15,32% of population, the expected data in 2020 is about 16%. The problem of this group becomes very essential social question. One of very important vital difficulties of that particular age is the problem with verbal communication, caused by the hearing disorders, very often stated in the older population. The hearing disorders (presbyacusis) are characterized by difficulties in speech understanding, the so called "social deafness", which often is a cause of psychical changes and isolation of persons with such hearing impairment. Because of its character, presbyacusis is very difficult in hearing rehabilitation. A new method of selection and fitting of hearing aids, adapted to the specificity of hearing disorders of older people is discussed. PMID- 17357668 TI - [The management of velopharyngeal insufficiency after pharyngeal augmentations and furlow surgery]. AB - INTRODUCTION: The term insuffisance velopalatine was first used by Larmoyez in 1892 r. Nowadays the term is used to denote the failure of the palate to produce velopharyngeal closure that would completely block the nasopharynx from the lower pharynx during physiological processes of swallowing, blowing, speaking, breathing and ventilation of the internal auditory canal. Numerous surgical techniques used in the treatment of VPI were described in the past 100 years. Several techniques have been used to decrease the velopharyngeal space, like operations aiming at bulging of the posterior pharyngeal wall and alternating "Z plasty" of the soft palate aiming at prolongation and improvement of the mobile function of the palate. MATERIAL AND METHOD: The prospective studies were carried on from May 2003 to October 2004. Patients with severe forms of VPI were qualified for surgical treatment by a phoniatrist, speech therapist and plastic surgeon. All the surgical procedures were performed by the same surgeon. Bulging of the posterior pharyngeal wall by means of corionic graft was performed in 8 patients as the first stage treatment followed by prolongation of the palate by means of Furlow's technique 6 months later. The anatomical conditions as well as speech quality prior to, after the first and the second procedure were evaluated on the basis of direct examination, speech assessment, nasofibroscopic examinations and nasometric measurements. RESULTS: Examinations performed 6 months after termination of surgical treatment revealed improvement or significant improvement in speech quality, especially concerning reduced nasality, speech intelligibility and decreased nasal airflow (on an average from 48% to 33%). Five patients rated in questionnaires the outcome of treatment as "significant improvement". CONCLUSION: Complex staged management consisting in bulging of the posterior pharyngeal wall and Furlow's operation appeared to be a successful modality of treatment in patients with severe forms of velo-pharyngeal insufficiency in about 75% of cases. PMID- 17357669 TI - [Renal cell carcinoma metastases to the head and neck]. AB - INTRODUCTION: The kidney is the third primary infraclavicular localization of malignant neoplasms metastasizing to the head and neck. The objective of this paper is to analyze the clinical presentation, diagnostic difficulties, management and outcome of metastatic renal cell carcinoma to the head and neck. MATERIAL AND METHODS: Retrospective review of four patients with renal cell carcinoma who have developed head and neck metastases and have been hospitalized in the ENT Department of the Medical University of Gdansk over the past 35 years. RESULTS: There were three women and one man in the examined material. The localizations of metastasizing renal cell carcinoma were: the larynx, the parotid gland, the cervical lymphnodes and the nasopharynx. In two patients metastatic tumor was the first clinical presentation of the disease and in the next two, time between treatment of the primary localization and occurring head and neck metastases was one and ten years. All patients, except one, were treated surgically. Two patients died, two are alive and the survival periods are one and three years. CONCLUSIONS: Renal cell carcinoma metastases to the head and neck region are infrequent but can cause difficulties in diagnosis and proper management. Despite of possibility of local excision, prognosis in metastasizing renal cell carcinoma is still unfavourable. PMID- 17357670 TI - [Assessment of the hearing results in tympanoplasties with the use of palisade technique]. AB - The cartilage has been successfuly used in reconstructive ear surgery for more than one hundred years. Histologic study of autografts cartilage (tragal or conchal) showed good long-term preservation of cartilage cells. The aim of this paper is to assess the hearing results in tympanoplasties with the use of cartilage palisade technique. MATERIAL AND METHODS: The retrospective analysis concerned 108 operated clinical cases. The cartilage palisade technique was performed in 28 tympanoplasties type I, 47 tympanoplasties type II, 21 tympanoplasties type III with columella and in 2 tympanoplasties type IV. Clinical assessment included otoscopy, test for eustachian tube ventilation, test with tuning fork, audiometry on a range 0,5, 1, 2 kHz and subjective evaluation based on questionaire. RESULTS: The Air Bone Gap (ABG) was noted as follows: < 10 dB among 67,8% of patients and 11-20 dB among 21,4% of patients in tympanoplasty type I. In tympanoplasty type II the ABG was responsively: < 10 dB - 80% patients, 11-20 dB - 10% patients. In the type III of tympanoplasty 40,4% of patients showed ABG < 10 dB and 42,5% of patients 11-20 dB. In the type III with columella we noted 15% patients with ABG < 10 dB and 65% of them with ABG 11-20 dB. CONCLUSIONS: The cartilage is a good autograft for reconstruction of the tympanic membrane, middle ear and the auditory wall because of stability and lack of secondary perforations. Long-term results in hearing are also satisfactory. PMID- 17357671 TI - [Long-term results after operation of otosclerosis with the use of partial stapedectomy technique after Heermann]. AB - INTRODUCTION: One of the best method for restoring hearing in otosclerosis is partial stapedectomy according to Heermann's proposition. MATERIAL AND METHODS: The retrospective study is refering to 98 patients with otosclerosis who underwent in 1987 year partial stapedectomy after Heermann. The assessment of long-term hearing results was based on audiometric examination after a lapse of 7 years and 15 years. RESULTS: 7 years after the operation we found the improvement of hearing in 90,6% of the patients with the air bone gap (ABG) < 10 dB and in 9,4% of them with ABG 11-20 dB. After 15 years the results were as follows: 23 patients with ABG 0-10 dB, 8 patients ABG 11-20 dB, 1 patients ABG 21-30 dB and 2 patients ABG > 30 dB. Any complications were noted. CONCLUSIONS: Partial stapedectomy is not only the safe method, but also very cheap with good results. PMID- 17357672 TI - [Magnetic resonance imaging in facial injuries and digital fusion CT/MRI]. AB - INTRODUCTION: Magnetic resonance images [MRI] and their digital fusion with computed tomography [CT] data, observed in patients affected with facial injuries, are presented in this study. MATERIAL AND METHODS: The MR imaging of 12 posttraumatic patients was performed in the same plains as their previous CT scans. Evaluation focused on quality of the facial soft tissues depicting, which was unsatisfactory in CT. Using the own "Dental Studio" programme the digital fusion of the both modalities was performed. RESULTS: Pathologic dislocations and injures of facial soft tissues are visualized better in MRI than in CT examination. Especially MRI properly reveals disturbances in intraorbital soft structures. CONCLUSIONS: MRI-based assessment is valuable in patients affected with facial soft tissues injuries, especially in case of orbita/sinuses hernia. Fusion CT/MRI scans allows to evaluate simultaneously bone structure and soft tissues of the same region. PMID- 17357673 TI - [Oral allergy syndrome--problem]. AB - History of oral allergy syndrome goes back to 1987 year, when Amlot for the first time used this name for pollen-food cross-reactive reactions. Since that time many kinds of various reactions between pollens and different food had been described. Is seems that after almost 20 years the knowledge about this highly prevalent phenomenon is still incomplete and not well known among specialist other than allergologists. We try to reach consensus on several aspects of this food-induced syndrome, which may be helpful in laryngological practice. It is very important especially for more severe immediate reactions which can occurred, like pharynx and larynx swelling with asphyxia, or anaphylaxis. Today OAS diagnosis is based on the patient's history and RAST. Most of patients gave a history of oral symptoms like oral irritation, throat tightness, lips, oral and throat swelling, oral mucosal blebs. This local symptoms quickly disappear and are not particularly serious but they may proceed to urticaria, asthma, abdominal pain and anaphylaxis. Treatment of OAS include; food avoidance, drugs and specific immunotherapy. Patients with pollen allergy should be informed about the possibility of hypersensitivity to certain fruits and vegetables. PMID- 17357674 TI - [Sigmoid sinus thrombosis in 5-year old child with acute otitis media and acquired CMV infection]. AB - Cytomegalovirus (CMV) belongs to Herpesvirida family and it occurs quite frequently in the human environment. It is a very important pathogen in persons with suppressed or lowered resistance. Having special kindship with epithelium, it may cause primary infection or reveal secondary influence in the latent form. Congenital CMV infection is a major cause of sensorineural hearing loss and neurological impairment in children. Otogenic complications may develop in patients with viral infection immunodeficiency. Aim of the paper was assessment of lateral sinus thrombosis (LST) in children with acute otitis media (AOM) and CMV infection. Authors present a case of LST in 5-year old child with AOM with mastoiditis and acquired CMV infection. In the first phase a disease appeared as mononucleosis-like infection with developing neurological signs resulting from meningitis. In the second phase the signs of acute otitis media, mastoiditis and lateral sinus thrombosis increased. Despite broad spectrum antibiotics therapy the intracranial complication developed which was surgically treated with good outcome. All the symptoms resulting from mastoiditis, LST and meningitis ceased. Clinical symptoms of the secondary CMV infection are rare in children. Complications may develop despite proper treatment of the ear and throat infections, and may result from immunodeficiency after CMV infection. PMID- 17357675 TI - [Chronic maxillary atelectasis (silent sinus syndrome)]. AB - INTRODUCTION: We discuss 3 cases with chronic maxillary atelectasis presenting as enophthalmos without any particular evidences of sinus pathology. MATERIAL AND METHODS: We report clinical features and imaging data of sinus atelectasis in 2 men and 1 woman, 20-39 years old. Only 1 patient complained of diplopia, in 2 patients we found allergic rhinitis, in 2 cases septal deviation. Hertel enophthalmometry demonstrated enophthalmos 1-4 mm. Evidences have lasted for 2-6 months. CT scans revealed unilateral complete antral opacification, inward bowing of the antral medial and postero-lateral walls and collapse of orbital floor. RESULTS: Three patients with enophthalmos and asymptomatic maxillary sinus disease were identified. All patients underwent successful functional endoscopic sinus surgery with endoscopic maxillary antrostomy and in one case anterior ethmoidectomy. Additionally septoplasty was performed in two cases. We did not need to repair orbital floor in any case. Patient with diplopia achieved spontaneous return of orbital floor to almost normal position with enophthalmos 1 mm and all three were asymptomatic. Intrasinus manometry was performed in one case and confirmed the presence of negative pressure (-2,8 cm H2O). CONCLUSION: Chronic maxillary atelectasis presenting as enophthalmos is a rare evidence and sinus component of the disease mostly remains asymptomatic. The most effective treatment is endoscopic maxillary antrostomy. PMID- 17357676 TI - [Bilateral internal laryngocele with open nasality--report of a case]. AB - Laryngocele is an abnormal saccule dilatation of the ventricle in direct communication with the laryngeal lumen. It is usually filled by air and mostly asymptomatic. This case is reported due to its rarity. A bilateral internal laryngocele with open nasality in 66-year-old man is described. Patient has been observed for 8 years with stable course of the disease and good general condition. Because the squamous cell carcinoma is known to occur in association with laryngocele necessity of control evaluation is very important. The etiology, classification, evaluation is discussed. PMID- 17357677 TI - [Glandular tularemia--case report]. AB - Tularemia is a rare zoonosis occuring in many clinical forms, including ulceral, glandular, oropharyngeal, pneumonic, and septic form. ENT specialists seeing their patients in ambulatory and emergency settings are most likely to encounter oropharyngeal and glandular form. Tularemia became widely discussed clinical entity in recent years due to its potential to being used as a biological weapon in acts of terrorism. Authors present a case of a 75 yrs old woman treated for atypical tonsillitis with suppurative cervical lymphadenitis. As infection with typical pathogens was ruled out and no improvement with antibiotics was observed, further evaluation was initiated. Malignancies and tuberculosis were excluded. Final diagnosis was established based on a serological test. Epidemiology, clinical manifestations, diagnostic procedures and treatment of tularemia, as well as diagnostic pitfalls are briefly discussed. PMID- 17357678 TI - [A case of parapharyngeal schwannoma (neurilemmoma) with thrombophlebitis coexisting]. AB - The Schwannoma of parapharyngeal space is uncommon tumor. The autors described a rare case of the schwannoma located in parapharyngeal space in 45-year-old man, with trombophlebitis coexciting. The tumor was removed trough the cervical approach. The post-surgery, follow-up examinations and CT check-up did not reveal any traces of recurrence. PMID- 17357679 TI - [The case of chronic subglottic oedema in a woman patient with hashimoto thyroiditis and gastroesophageal reflux disease]. AB - The case of a thirty year old woman patient with subglottic oedema lasting for two years and causing periodically recurrent laryngeal breathlessness has been described. Multispecialistic diagnostic procedure as well as the clinical course of the disease have been presented. The issue of the degree to which the Hashimoto disease or the gastroesophageal reflux disease may be the cause of the oedema has been discussed. PMID- 17357680 TI - [Polychondritis relapsans--a case report]. AB - INTRODUCTION: The relapsing polychondritis (RP) rarely occurs and it's classified to connective tissue diseases. Woman from the age of 35 to 45 suffer most often from this types of collagenosis. Typical features of all collagenosis are the connective tissue inflammation and the presence of autoantibodies in the patient's peripheral blood. The RP disease relies on general polychondritis with gradually cicatrization and fibromatosis of different cartilages of the body. Inflammatory process leads to destruction of the collagen type A by autoantibodies. The main symptom of RP is the inflammation of the auricle, nose, nasal septum, laryngeal, tracheal and bronchial cartilages, which causes deformations of these organs. The polyarthritis without a distortion accompanies to cartilages changes. The heart and blood vessels connective tissue changes have been hardly described but they can lead to develop acquired valvular disease and aneurysms in large blood vessels. An increase of the erythrocyte sedimentation rete, the anemia and the leucocytosis have been observed. The auricle ache, edema and hyperemia of the auricle and general polyarthritis are often the beginning of the RP disease. The external and intranasal polychondritis with later nose deformations are the next symptoms of that disease. Changes in the nasal and auricular cartilages are sometimes single sings of RP. However the inflammatory process can develop in laryngeal and tracheal cartilages producing the respiratory insufficiency and it leads to the death of 25% patients. In the treatment of RP anti-inflammatory drugs are used in the first period of disease. Afterwards patients are treated with steroids, metothrexate and cyclophosphamide. The latest anticytokinne drug are applied by RP treatment. MATERIAL AND METHODS: A 46 years old woman was admitted to Otolaryngology Department with edema chorda vocalis, dysphonia and dyspnoe. After operation she had respiratory insufficiency. This woman was admitted to Otolaryngology Department many times with dyspnea, which was treating with steroids and terminally with tracheotomy. RESULTS: Histology of the tracheal cartilages showed the PR. From this time the woman was pharmacology treating in another department of rheumatology. CONCLUSIONS: The RP is rarely occurs disease, who is very difficult to diagnosis end treatment, and many times leads to death. PMID- 17357681 TI - [Hemangioma cavernous of the nasal cavity and the maxillary sinus--case report and review of the literature]. AB - Hemangiomas of the nasal cavity and especially paranasal sinuses are very rare. Authors reported a case of hemangioma cavernous of the nasal cavity and maxillary sinus in a 34-year-old women. Diagnostic procedures, therapeutic intervention were presented and literature reviewed. PMID- 17357682 TI - [A case of giant-size mucoepidermoid carcinoma of parotid gland]. AB - INTRODUCTION: A mucoepidermoid carcinoma is a rare disease of the salivary glands. It usually occurs as a small tumor (a few centimeters diameter). The most important diagnostic procedure for the treatment is a histological examination. MATERIAL AND METHODS: We present the case of 71 years old woman with giant in size tumor of the left parotid gland. The tumor had developed in the three years' time and no paresis of the facial nerve had occurred during that time. Preoperative fine needle aspiration biopsy of the parotid gland masses showed pleomorphic adenoma cells. RESULTS: The surgery treatment was introduced. The function of the facial nerve was preserved. The histological examination result was mucoepidermoid carcinoma. We observed local recurrence of the tumor five months after the operation. But there was still no facial nerve paralysis. The patient was submitted to the radiotherapy treatment. CONCLUSION: The big size of the tumor may be an obstacle in full resection during an operation. The false negative results during a fine needle aspiration and preserved normal function of the facial nerve can cause correct treatment as an extremely difficult goal. PMID- 17357683 TI - [Intractable epistaxis in a 3,5-year-old child]. AB - Intractable epistaxis can be a serious problem in children. The authors present the case of a 3,5 year old child with a history of nasal bleeding lasting 3 years which was successfully managed by superselective embolisation of the internal maxillary artery. PMID- 17357684 TI - [History of otolaryngology department of Military Medical Academy]. AB - Establishing the Chair of Laryngology with the Clinic of the Military Medical Academy was connected with inauguration of the Military Medical Academy in Lodz on the 1st July, 1958 (the Resolution of the Cabinet Council No. 477 / 57 dated 7th November, 1957 and the Order of the Minister of National Defence No. 03 / Org. dated 19th May, 1958) on the basis of the Military Centre of Medical Training, the Central Clinical Hospital in Lodz and the Central Hospital of the Ministry of National Defence in Warsaw. In fact the Chair of Laryngology with the Clinic of the Military Medical Academy was established in September 1958 with Major Antoni Kwilman, M.D. - senior lecturer - appointed to be a temporarily performing duties head of the institution until April 1959. Considering its successive Heads the forty-five years history of the Otolaryngology Clinic at the Military Medical Academy can be divided into four periods. Period I. In April 1959 Assistant Professor Jozef Borsuk, MD, PhD (Professor later) was appointed to be the first Head of the Chair of Laryngology and the Clinic. Within scientific scope the Chair cooperated with the Nofer Institute of Occupational Medicine in Lodz, the Military Sanatorium Unit in Ciechocinek and foreign Centres from the then German Democratic Republic and Czechoslovakia. Period II. Since the 1st October 1974 the Chair of Laryngology with the Clinic and since the 1st November that year the Otolaryngological Clinic at the Institute of Sense Organs the Military Medical Academy was run by Assistant Professor Bo2ydar Latkowski, MD, PhD - another Head appointed by the Minister of National Defence - who managed it until the 30th November 1987 and was the only civil Head of the Clinic. Period III. On the 1st December 1987 the third Head got in charge of the Otolaryngological Clinic at the Military Medical Academy - the then senior lecturer at the Clinic - Piotr Zalewski MD, PhD (the Military Medical Academy graduate). Period IV. By open competition on the 1st day of October 2003 Prof. Jurek Olszewski, MD,PhD was appointed to the Head of the Otolaryngology and Phonoaudiological Rehabilitation Clinic and simultaneously has been occupying the position of the Dean at the Faculty of Physiotherapy the Medical University of Lodz. PMID- 17357685 TI - [The otorhinolaryngological achievements of surgeon Hipolit Korzeniowski (1827 1897)]. AB - The professional and scientific activities of Hipolit Korzeniowski (1827-1879), an eminent Varsovian surgeon, his thorough medical education in various European centries is shortly outlined. He was a head of the surgical ward especially at the Infant Jesus Hospital in Warsaw and at the medical schools in Warsaw. Korzeniowski's succesful surgical treatment of rhinolaryngological diseases, such as scarlet fever of ear, treatment of deaf-mutism, sinusitis paranasales, operations of jaws, plastic reconstruction of the palate, foreign bodies of larynx, tracheotomy in the tuberculosis of larynx, are described in some more detail. PMID- 17357686 TI - [Clinical effectiveness of betahistine in monotherapy of vertigo for different etiology]. AB - Vertigo is common symptom in clinical practice and among cerebrovascular and otological diseases. The aim of this clinical study was to evaluate the effect of betahistine dihydrochloride (Betaserc) on patients with long lasted dizziness. Enrolled in the study were 33 parients at the age between 32 and 80 years whom were treated 16 mg doses of betaserc three times daily et the time 12 weeks. The methods of following investigation was clinical examination, subjective and objective examination and carry out individual questionnaires once a four weeks. On the basis of experiment it was showed that a distinct clinical improvement in the group of 33 patients was in above 66% patients and medication is well tolerated and suitable for long-term treatment. PMID- 17357687 TI - [Treatment of hepatitis: new ways, new hopes and new challenges]. PMID- 17357688 TI - [Peptic diseases]. AB - There are no real therapeutical acquisitions in the year 2006. The latest breakthroughs related to peptic disease treatment are the subject of this article. In particular various therapeutic procedures in reflux disease, including Barrett's oesophagus are developed here. Two important items were emphasized in the treatment of gastric and duodenal ulcers, in particular Helicobacter pylori eradication and the treatment of bleeding ulcer. Prophylaxis of gastrointestinal lesions due to AINS is also approached in detail. PMID- 17357689 TI - [Intestinal inflammatory diseases]. AB - There was no real therapeutic advances in inflammatory bowel diseases last year. In addition to infliximab, new anti-TNF-alpha agents will soon become available. PMID- 17357690 TI - [Management of chronic viral hepatitis]. AB - This review highlights recent progress in the management of chronic hepatitis B, C and D. New nucleoside and nucleotide analogs have recently been approved and are currently being evaluated for the treatment of chronic hepatitis B. At the same time, resistance is becoming an increasingly common clinical problem. Efforts are currently being made to individualize treatment regimens for patients with chronic hepatitis C, with the aim of enhancing efficacy and improving tolerability. Finally, recent studies using pegylated interferon-alpha have shown promising results for the treatment of chronic hepatitis D. PMID- 17357691 TI - [Chronic pancreatitis]. AB - New insights in the pathogenesis, classification and the identification of novel risk factors and novel mutations involved in pancreas divisum and in idiopathic pancreatitis have been introduced. Despite novel diagnosis methods, the identification of early pancreatitis, of pancreatitis with minimal morphological changes and the differential diagnosis between chronic pancreatitis and pancreatic carcinoma remain challenges. Treatment of pain associated with pancreatitis remains also difficult; evidence for endoscopic and surgical approaches is still missing. These new discoveries in pathogenesis, etiology and diagnosis methods did not yet lead to improved diagnosis and treatment of chronic pancreatitis. PMID- 17357692 TI - [Functional dyspepsia, constipation and faecal incontinence]. AB - Regarding functional dyspepsia, constipation, fecal incontinence, the main therapeutic acquisitions of the period are the following: for functional dyspepsia, remember that alarm signs are not absolute signs of seriousness; for constipation, encourage and repeat advises such as physical exercise; for fecal incontinence the transcutaneous neuro-modulation and the TENS (Transcutaneous Electrical Nerve Stimulation) are potential alternatives to sacral neuro modulation. PMID- 17357693 TI - [Pharmacovigilance and teratovigilance]. AB - While 2006 did not record as many upsetting revelations of adverse drug reactions as the previous few years, still some data have been produced, which modulate the safety profile of drugs and deserve the attention of the prescribers: cardiovascular events under erythropoietins, macular oedema under rosiglitazone, vascular and renal complications of aprotinine, drawbacks of long-term linezolide administration, intracranial haemorrhage under tipranavir, anyphylaxis with pegaptanib, cardiototoxicity of imatinib, lymphomas with infliximab, bone pain and aches under bisphosphonates, cardiovascular events related to methylphenidate, congenital anomalies ascribed to paroxetine and lamotrigine, neonatal pulmonary hypertension related to serotonine reuptake inhibitors, infantile respiratory depression under promethazine. PMID- 17357695 TI - [Fear only breeds disadvantages]. PMID- 17357694 TI - [No one is supposed to ignore... that physicians have lost the control of the psychotherapeutic mandate in favor of the insurers]. PMID- 17357696 TI - [January 2007, the epizootic is always present]. PMID- 17357697 TI - [On genomics applied to neoplasms (I)]. PMID- 17357698 TI - [Tobacco departed, the end for smoke spirals (I)]. PMID- 17357699 TI - [Intermediaries]. PMID- 17357700 TI - New cases seen at genitourinary medicine clinics: England 1996. AB - Statistics from genitourinary medicine clinics provide the most comprehensive source of data on the epidemiology of sexually transmitted infections (STI) in England. This is the first report to be published in a journal since 1986. The total number of diagnoses made increased by 5% between 1995 and 1996, the increase for females (8%) being greater than that for males (3%). Total diagnoses of acute STIs rose by 7% between 1995 and 1996. Diagnoses of gonorrhoea, genital Chlamydia trachomatis, and genital warts rose by 20%, 11%, and 5%, respectively, over the same period. Rises were most pronounced among teenagers and homosexual and bisexual men. These data suggest that these groups should continue to be a focus for sexual health education and intervention programmes. The behavioural and sociodemographic changes behind these increases are impossible to determine without further research. Many of the conditions for which a rising trend has been observed are curable. These trends suggest that safer practices in sexual behaviour are being neglected, which could leave many individuals vulnerable to HIV infection. PMID- 17357701 TI - The most expensive painting in the world. PMID- 17357702 TI - Shrinkage in the apparent size of cylindrical objects. AB - A novel illusion in apparent size is reported. We asked observers to estimate the width and depth of vertically oriented elliptic cylinders depicted with texture or luminance gradients (experiment 1), or the height of horizontally oriented elliptic cylinders depicted with binocular disparity (experiment 2). The estimated width or height of cylinders showed systematic shrinkage in the direction of the gradual depth change. The dissimilarity of 2-D appearance amongst our stimuli implies a large variation in spatial-frequency components and brightness contrasts, eliminating the possibility that these parameters contributed to the illusion. Also, the mechanism inappropriately triggered by pictorial depth cues (eg size scaling) may be irrelevant, because the illusion was obtained even when binocular disparity alone specified the shape of the cylinders. The illusion demonstrated here suggests that our visual system may determine the size of 3-D objects by accounting for their depth structures. PMID- 17357703 TI - Localized attentional interference affects object individuation, not feature detection. AB - Modern theorists conceptualize visual selective attention as a competition between object representations for the control of extrastriate receptive fields, an account supported by the finding that attentional selection of one stimulus can degrade processing of nearby stimuli. In the present study the conditions that produce reciprocal interference between attended stimuli are examined. Each display contained either no, one, or two feature-defined target items among an array of homogeneous distractors. Observers performed two tasks, feature detection and object individuation. The feature-detection task required observers to determine if any targets were present within the display. The object individuation task required observers to determine if the number of targets was exactly two. Spatially mediated interference between target pairs occurred in the object-individuation task, but had no effect on feature detection. Results suggest that localized interference between attended stimuli occurs only when observers are required to resolve the features of individual objects, consistent with the competitive interaction models of attention. PMID- 17357704 TI - Pigeons' recognition of partially occluded objects depends on specific training experience. AB - DiPietro et al (2002 Perception 31 1299-1312) reported a dramatic improvement in pigeons' recognition of partially occluded objects after the birds had been trained to recognize objects that were placed on top of another surface. Here, we investigated whether training with partially erased stimuli or with notched stimuli that had a thin gap between the object and another surface would similarly enhance pigeons' recognition of partially occluded objects. We found that erased training had no effect on the birds' recognition of partially occluded objects. Training pigeons to recognize notched objects improved their performance with the same objects when they were partially occluded; but this improvement did not transfer to novel objects, a result that DiPietro et al reported after on-top training. Together, the present results and those of DiPietro et al implicate prior experience as a key factor in pigeons' recognition of partially occluded objects. Training experiences which improve recognition of partially occluded objects may do so because they improve decomposition of complex two-dimensional scenes by pigeons into separate entities. PMID- 17357705 TI - Visual binding of English and Chinese word parts is limited to low temporal frequencies. AB - Some perceptual mechanisms manifest high temporal precision, allowing reports of visual information even when that information is restricted to windows smaller than 50 ms. Other visual judgments are limited to much coarser time scales. What about visual information extracted at late processing stages, for which we nonetheless have perceptual expertise, such as words? Here, the temporal limits on binding together visual word parts were investigated. In one trial, either the word 'ball' was alternated with 'deck', or 'dell' was alternated with 'back', with all stimuli presented at fixation. These stimuli restrict the time scale of the rod identities because the two sets of alternating words form the same image at high alternation frequencies. Observers made a forced choice between the two alternatives. Resulting 75% thresholds are restricted to 5 Hz or less for words and nonword letter strings. A similar result was obtained in an analogous experiment with Chinese participants viewing alternating Chinese characters. These results support the theory that explicit perceptual access to visual information extracted at late stages is limited to coarse time scales. PMID- 17357706 TI - Effects of context on a visual 3-D pointing task. AB - We examined the effects of egocentric and contextual references on a 3-D exocentric pointing task. Large systematic deviations were found for the slant (angle in the horizontal plane). For most observers, the deviations were smaller when the veridical pointing direction was parallel to a wall. For some observers the size of the deviations was also dependent on whether the veridical pointing direction was frontoparallel or not. For the tilt (angle in the vertical plane), the deviations were smaller and less systematic. Hence, although observers show comparable systematic deviations, the way in which the presence of structure in an environment is used for judging positions of objects is observer-dependent. PMID- 17357707 TI - Expertise in pictorial perception: eye-movement patterns and visual memory in artists and laymen. AB - In two sessions with free scanning and memory instructions, eye-movement patterns from nine artists were compared with those of nine artistically untrained participants viewing 16 pictures representing a selection of categories from ordinary scenes to abstraction: 12 pictures were made to accommodate an object oriented viewing mode (selection of recognisable objects), and a pictorial viewing mode (selection of more structural features), and 4 were abstract. The artistically untrained participants showed preference for viewing human features and objects, while the artists spent more scanning time on structural/abstract features. A group by session interaction showed a change of viewing strategy in the artists, who viewed more objects and human features in the memory task session. A verbal test of recall memory showed no overall difference in the number of pictures remembered, but the number of correctly remembered pictorial features was significantly higher for artists than for the artistically untrained viewers, irrespective of picture type. No differences in fixation frequencies/durations were found between groups across sessions, but a significant task-dependent-group by session interaction of fixation frequency/duration showed that the artistically untrained participants demonstrated repetition effects in fewer, longer fixations with repeated viewing, while the opposite pattern obtained for the artists. PMID- 17357708 TI - The influence of visual experience on visual and spatial imagery. AB - Differences are reported between blind and sighted participants on a visual imagery and a spatial-imagery task, but not on an auditory-imagery task. For the visual-imagery task, participants had to compare object forms on the basis of a (verbally presented) object name. In the spatial-imagery task, they had to compare angular differences on the basis of the position of clock hands on two clock faces, again only on the basis of verbally presented clock times. Interestingly, there was a difference between early-blind and late-blind participants on the visual-imagery and the spatial-imagery tasks: late-blind participants made more errors than sighted people on the visual-imagery task, while early-blind participants made more errors than sighted people on the spatial-imagery task. This difference suggests that, for visual (form) imagery, people use the channel currently available (haptic for the blind; visual for the sighted). For the spatial-imagery task in this study reliance on haptic processing did not seem to suffice, and people benefited from visual experience and ability. However, the difference on the spatial-imagery task between early blind and sighted people in this study might also be caused by differences in experience with the analogue clock faces that formed the basis for the spatial judgments. PMID- 17357709 TI - Relative sensitivities to large-field optic-flow patterns varying in direction and speed. AB - Motion in depth results in radial optic-flow patterns. Forward motion results in radially expanding patterns, whereas backward motion generates contracting patterns. Radial optic-flow patterns are typically represented with a positive speed gradient, ie zero speed at the point of fixation, and maximum speed at the periphery. However, the actual speed profile in such a stimulus will depend upon the relative depth of objects in the scene. Using large-field stimuli (82 deg diameter) we determined relative sensitivities to radial expansion and contraction patterns and also to various types of speed gradients: positive, negative, random, and flat. We found that, even when large-field stimuli are used, observers are more sensitive to radially contracting patterns than to expanding patterns. Sensitivity to the positive speed gradient was not consistently different from either the negative or random gradients. Sensitivity to the flat gradient depended upon the speed of the stimuli. The finding of greater sensitivity to radial contraction is discussed in terms of the functional requirements involved in the use of optic-flow signals in maintaining balance. On the basis of the present findings, the utility of comparing psychophysical results based on thresholds against physiological data based on suprathreshold stimuli is also discussed. PMID- 17357710 TI - Additivity of retinal and pursuit velocity in the perceptions of depth and rigidity from object-produced motion parallax. AB - Two psychophysical experiments were conducted to investigate the mechanism that generates stable depth structure from retinal motion combined with extraretinal signals from pursuit eye movements. Stimuli consisted of random dots that moved horizontally in one direction (ie stimuli had common motion on the retina), but at different speeds between adjacent rows. The stimuli were presented with different speeds of pursuit eye movements whose direction was opposite to that of the common retinal motion. Experiment 1 showed that the rows moving faster on the retina appeared closer when viewed without eye movements; however, they appeared farther when pursuit speed exceeded the speed of common retinal motion. The 'transition' speed of the pursuit eye movement was slightly, but consistently, larger than the speed of common retinal motion. Experiment 2 showed that parallax thresholds for perceiving relative motion between adjacent rows were minimum at the transition speed found in experiment 1. These results suggest that the visual system calculates head-centric velocity, by adding retinal velocity and pursuit velocity, to obtain a stable depth structure. PMID- 17357711 TI - The stereoscopic sliver: a comparison of duration thresholds for fully stereoscopic and unmatched versions. AB - Just as positional disparities of image features seen with both eyes provide depth information, the presence of an area visible to one eye but not the other within a binocularly viewed scene can indicate an occlusion at a depth discontinuity. The close geometrical association between these two kinds of cues suggests they may both be exploited by stereopsis. To investigate this, we developed a novel binocular stimulus entirely lacking in classical disparity that contains an unmatched vertical sliver which elicits a warping of the surrounding surface to accommodate a depth discontinuity. We measured depth-discrimination performance at a range of stimulus durations, correcting for variations in stimulus visibility, to characterise the decline of the efficacy of the depth signal with limited integration time. Results show a close correspondence of performance for similar stimuli with unmatched features and classical binocular disparity across a sixtyfold range of viewing durations, supporting the notion of a close association between the two types of cues in human stereopsis. Control experiments excluded simple eye-of-origin cues and long-range false matches as explanatory factors. PMID- 17357712 TI - Perception of motion transparency in 5-month-old infants. AB - We investigated the perceptual development of motion transparency in 3- to 5 month-old infants. In two experiments we tested a total of 55 infants and examined their preferential looking behaviour. In experiment 1, we presented transparent motion as a target, and uniform motion as a non-target consisting of random-dot motions. We measured the time during which infants looked at the target and non-target stimuli. In experiment 2, we used paired-dot motions (Qian et al, 1994 Journal of Neuroscience 14 7357-7366) as non-targets and also measured target looking time. We calculated the ratio of the target looking time to the total target and no-target looking time. In both experiments we controlled the dot size, speed, the horizontal travel distance of the dots, and the motion pattern of the dots. The results demonstrated that 5-month-old infants showed a statistically significant preference for motion transparency in almost all stimulus conditions, whereas the preference in 3- and 4-month-old infants depended on stimulus conditions. These results suggest that the sensitivity to motion transparency was robust in 5-month-olds, but not in 3- and 4-month-olds. PMID- 17357713 TI - Look who's talking: recognizing friends from visible articulation. AB - We tested whether isolated visible articulatory information can be used for identifying familiar speakers. A facial point-light methodology was used to isolate the visible articulation of seven speakers. These point-light video clips were then shown to nine participants who had long-term personal interactions with the speakers. Results revealed that participants could identify the speakers at better than chance levels when the faces were shown articulating, but not when the faces were shown without movement. The results indicate that visible articulatory information can be used to identify speakers. PMID- 17357714 TI - The transducer model for contrast detection and discrimination: formal relations, implications, and an empirical test. AB - The transducer function mu for contrast perception describes the nonlinear mapping of stimulus contrast onto an internal response. Under a signal detection theory approach, the transducer model of contrast perception states that the internal response elicited by a stimulus of contrast c is a random variable with mean mu(c). Using this approach, we derive the formal relations between the transducer function, the threshold-versus-contrast (TvC) function, and the psychometric functions for contrast detection and discrimination in 2AFC tasks. We show that the mathematical form of the TvC function is determined only by mu, and that the psychometric functions for detection and discrimination have a common mathematical form with common parameters emanating from, and only from, the transducer function mu and the form of the distribution of the internal responses. We discuss the theoretical and practical implications of these relations, which have bearings on the tenability of certain mathematical forms for the psychometric function and on the suitability of empirical approaches to model validation. We also present the results of a comprehensive test of these relations using two alternative forms of the transducer model: a three-parameter version that renders logistic psychometric functions and a five-parameter version using Foley's variant of the Naka-Rushton equation as transducer function. Our results support the validity of the formal relations implied by the general transducer model, and the two versions that were contrasted account for our data equally well. PMID- 17357715 TI - Intrinsic uncertainty explains second responses. AB - In the simplest form of signal-detection theory (SDT), all stimuli give rise to equal-variance Gaussian probability density functions (PDFs) of sensation, with means proportional to stimulus intensity. As this simple SDT cannot accurately describe psychometric functions for two-alternative forced-choice (2AFC) detection experiments, it is commonly modified in one of two ways: with a non linear transducer or intrinsic uncertainty. Most results can adequately be explained by either modification, but Swets et al.'s (1961) two-response 4AFC (2R4AFC) detection experiment is an exception. Simple SDT cannot predict the relationship between first- and second-response accuracies and non-linear transduction does not help. A previously unacknowledged facet of intrinsic uncertainty is that the same uncertainty required to fit 2AFC psychometric functions also produces an excellent fit to Swets et al.'s 2R4AFC results, without requiring any additional assumptions. This result is derived within the context of a primer on SDT. PMID- 17357716 TI - Evaluation of a 'bias-free' measure of awareness. AB - The derivation of a reliable, subjective measure of awareness that is not contaminated by observers' response bias is a problem that has long occupied researchers. Kunimoto et al. (2001) proposed a measure of awareness (a') which apparently meets this criterion: a' is derived from confidence ratings and is based on the intuition that confidence should reflect awareness. The aim of this paper is to explore the validity of this measure. Some calculations suggested that, contrary to Kunimoto et al.'s intention, a' can vary as a result of changes in response bias affecting the relative proportions of high- and low-confidence responses. This was not evident in the results of Kunimoto et al.'s original experiments because their method may have artificially 'clamped' observers' response bias close to zero. A predicted consequence of allowing response bias to vary freely is that it can result in a' varying from negative, through zero, to positive values, for a given value of discriminability (d'). We tested whether such variations are likely to occur in practice by employing Kunimoto et al.'s paradigm with various modifications, notably the removal of constraints upon the proportions of low- and high-confidence responses, in a visual discrimination task. As predicted, a' varied with response bias in all participants. Similar results were found when a' was calculated from pre-existing data obtained from a patient with blindsight: a' varied through a range of positive results without approaching zero, which is inconsistent with his well-documented lack of awareness. A second experiment showed how response bias could be manipulated to yield elevated values of a'. On the basis of these findings we conclude that Kunimoto's measure is not as impervious to response bias as was originally assumed. PMID- 17357717 TI - Low-level correlations between object properties and viewpoint can cause viewpoint-dependent object recognition. AB - Viewpoint-dependent recognition performance of 3-D objects has often been taken as an indication of a viewpoint-dependent object representation. This viewpoint dependence is most often found using metrically manipulated objects. We aim to investigate whether instead these results can be explained by viewpoint and object property (e.g. curvature) information not being processed independently at a lower level, prior to object recognition itself. Multidimensional signal detection theory offers a useful framework, allowing us to model this as a low level correlation between the internal noise distributions of viewpoint and object property dimensions. In Experiment 1, we measured these correlations using both Yes/No and adjustment tasks. We found a good correspondence across tasks, but large individual differences. In Experiment 2, we compared these results to the viewpoint dependence of object recognition through a Yes/No categorization task. We found that viewpoint-independent object recognition could not be fully reached using our stimuli, and that the pattern of viewpoint dependence was strongly correlated with the low-level correlations we measured earlier. In part, however, the viewpoint was abstracted despite these correlations. We conclude that low-level correlations do exist prior to object recognition, and can offer an explanation for some viewpoint effects on the discrimination of metrically manipulated 3-D objects. PMID- 17357718 TI - Cue combination and the effect of horizontal disparity and perspective on stereoacuity. AB - Relative depth judgments of vertical lines based on horizontal disparity deteriorate enormously when the lines form part of closed configurations (Westheimer, 1979). In studies showing this effect, perspective was not manipulated and thus produced inconsistency between horizontal disparity and perspective. We show that stereoacuity improves dramatically when perspective and horizontal disparity are made consistent. Observers appear to use unhelpful perspective cues in judging the relative depth of the vertical sides of rectangles in a way not incompatible with a form of cue weighting. However, 95% confidence intervals for the weights derived for cues usually exceed the a-priori [0-1] range. PMID- 17357719 TI - Local and relational judgements of surface colour: constancy indices and discrimination performance. AB - Colour constancy is generally assumed to arise from a combination of perceptual constancy mechanisms operating to partially discount illumination changes and relational mechanisms involved in judging the colour relationships between object surfaces. Here we examined the characteristics of these mechanisms using a 'yes/no' task. Subjects judged whether a target colour patch embedded in an array of coloured patches (a) stayed the same across a simulated temporal illuminant change (local colour judgement), or (b) changed in a manner consistent with the illuminant change (relational colour judgement). The colour of the target patch remained constant in one-third of the trials, changed in accord with the illuminant shift in another third, and shifted partially with the illuminant change in the remaining third. We found that perceptual constancy was relatively weak and relational constancy strong, as assessed using a modified colour constancy index. Randomising the spatial positions of coloured patches across the illuminant change did not affect subjects' constancy indices. Application of signal detection analysis revealed some otherwise hidden effects. In the case of relational judgements, subjects adopted more conservative criteria (fewer true and false positives) with randomisation, maintaining a constant level of discrimination performance (d'). For local judgements, randomisation led to small increases in performance but no changes in criteria. We conclude that signal detection theory provides a useful tool to supplement conventional approaches to understanding colour constancy. PMID- 17357720 TI - Perceptual distance and the moon illusion. AB - The elevated moon usually appears smaller than the horizon moon of equal angular size. This is the moon illusion. Distance cues may enable the perceptual system to place the horizon moon at an effectively greater distance than the elevated moon, thus making it appear as larger. This explanation is related to the size distance invariance hypothesis. However, the larger horizon moon is usually judged as closer than the smaller zenith moon. A bias to expect an apparently large object to be closer than a smaller object may account for this conflict. We designed experiments to determine if unbiased sensitivity to illusory differences in the size and distance of the moon (as measured by d') is consistent with SDIH. A moon above a 'terrain' was compared in both distance and size to an infinitely distant moon in empty space (the reduction moon). At a short distance the terrain moon was adjudged as both closer and smaller than the reduction moon. But these differences could not be detected at somewhat greater distances. At still greater distances the terrain moon was perceived as both more distant and larger than the reduction moon. The distances at which these transitions occurred were essentially the same for both distance and size discrimination tasks, thus supporting SDIH. PMID- 17357721 TI - A new SURE approach to image denoising: interscale orthonormal wavelet thresholding. AB - This paper introduces a new approach to orthonormal wavelet image denoising. Instead of postulating a statistical model for the wavelet coefficients, we directly parametrize the denoising process as a sum of elementary nonlinear processes with unknown weights. We then minimize an estimate of the mean square error between the clean image and the denoised one. The key point is that we have at our disposal a very accurate, statistically unbiased, MSE estimate--Stein's unbiased risk estimate--that depends on the noisy image alone, not on the clean one. Like the MSE, this estimate is quadratic in the unknown weights, and its minimization amounts to solving a linear system of equations. The existence of this a priori estimate makes it unnecessary to devise a specific statistical model for the wavelet coefficients. Instead, and contrary to the custom in the literature, these coefficients are not considered random anymore. We describe an interscale orthonormal wavelet thresholding algorithm based on this new approach and show its near-optimal performance--both regarding quality and CPU requirement -by comparing it with the results of three state-of-the-art nonredundant denoising algorithms on a large set of test images. An interesting fallout of this study is the development of a new, group-delay-based, parent-child prediction in a wavelet dyadic tree. PMID- 17357722 TI - Efficient architectures for two-dimensional discrete wavelet transform using lifting scheme. AB - Novel architectures for 1-D and 2-D discrete wavelet transform (DWT) by using lifting schemes are presented in this paper. An embedded decimation technique is exploited to optimize the architecture for 1-D DWT, which is designed to receive an input and generate an output with the low- and high-frequency components of original data being available alternately. Based on this 1-D DWT architecture, an efficient line-based architecture for 2-D DWT is further proposed by employing parallel and pipeline techniques, which is mainly composed of two horizontal filter modules and one vertical filter module, working in parallel and pipeline fashion with 100% hardware utilization. This 2-D architecture is called fast architecture (FA) that can perform J levels of decomposition for N * N image in approximately 2N2(1 - 4(-J))/3 internal clock cycles. Moreover, another efficient generic line-based 2-D architecture is proposed by exploiting the parallelism among four subband transforms in lifting-based 2-D DWT, which can perform J levels of decomposition for N * N image in approximately N2(1 - 4(-J))/3 internal clock cycles; hence, it is called high-speed architecture. The throughput rate of the latter is increased by two times when comparing with the former 2-D architecture, but only less additional hardware cost is added. Compared with the works reported in previous literature, the proposed architectures for 2-D DWT are efficient alternatives in tradeoff among hardware cost, throughput rate, output latency and control complexity, etc. PMID- 17357723 TI - Iterative voting for inference of structural saliency and characterization of subcellular events. AB - Saliency is an important perceptual cue that occurs at different levels of resolution. Important attributes of saliency are symmetry, continuity, and closure. Detection of these attributes is often hindered by noise, variation in scale, and incomplete information. This paper introduces the iterative voting method, which uses oriented kernels for inferring saliency as it relates to symmetry. A unique aspect of the technique is the kernel topography, which is refined and reoriented iteratively. The technique can cluster and group nonconvex perceptual circular symmetries along the radial line of an object's shape. It has an excellent noise immunity and is shown to be tolerant to perturbation in scale. The application of this technique to images obtained through various modes of microscopy is demonstrated. Furthermore, as a case example, the method has been applied to quantify kinetics of nuclear foci formation that are formed by phosphorylation of histone gammaH2AX following ionizing radiation. Iterative voting has been implemented in both 2-D and 3-D for multi image analysis. PMID- 17357724 TI - Robust and accurate registration of 2-D electrophoresis gels using point matching. AB - Point-matching is a widely applied image registration method and many algorithms have been developed. Registration of 2-D electrophoresis gels is an important problem in biological research that presents many of the technical difficulties that beset point-matching: large numbers of points with variable densities, large nonrigid transformations between point sets, paucity of structural information and large numbers of unmatchable points (outliers) in either set. In seeking the most suitable algorithm for gel registration we have evaluated a number of approaches for accuracy and robustness in the face of these difficulties. Using synthetic images we test combinations of three algorithm components: correspondence assignment, distance metrics and image transformation. We show that a version of the iterated closest point (ICP) algorithm using a non Euclidean distance metric and a robust estimation of transform parameters provides best performance, equalling SoftAssign in the presence of moderate image distortion, and providing superior robustness against large distortions and high outlier proportions. From this evaluation we develop a gel registration algorithm based on robust ICP and a novel distance metric combining Euclidean, shape context and image-related features. We demonstrate the accuracy of gel matching using synthetic distortions of real gels and show that robust estimation of transform parameters using M-estimators can enforce inverse consistency, ensuring that matching results are independent of the order of the images. PMID- 17357725 TI - A hybrid Eulerian-Lagrangian approach for thickness, correspondence, and gridding of annular tissues. AB - We present a novel approach to efficiently compute thickness, correspondence, and gridding of tissues between two simply connected boundaries. The solution of Laplace's equation within the tissue region provides a harmonic function whose gradient flow determines the correspondence trajectories going from one boundary to the other. The proposed method uses and expands upon two recently introduced techniques in order to compute thickness and correspondences based on these trajectories. Pairs of partial differential equations are efficiently computed within an Eulerian framework and combined with a Lagrangian approach so that correspondences trajectories are partially constructed when necessary. Examples are presented in order to compare the performance of this method with those of the pure Lagrangian and pure Eulerian approaches. Results show that the proposed technique takes advantage of both the speed of the Eulerian approach and the accuracy of the Lagrangian approach. PMID- 17357726 TI - Robust rate-control for wavelet-based image coding via conditional probability models. AB - Real-time rate-control for wavelet image coding requires characterization of the rate required to code quantized wavelet data. An ideal robust solution can be used with any wavelet coder and any quantization scheme. A large number of wavelet quantization schemes (perceptual and otherwise) are based on scalar dead zone quantization of wavelet coefficients. A key to performing rate-control is, thus, fast, accurate characterization of the relationship between rate and quantization step size, the R-Q curve. A solution is presented using two invocations of the coder that estimates the slope of each R-Q curve via probability modeling. The method is robust to choices of probability models, quantization schemes and wavelet coders. Because of extreme robustness to probability modeling, a fast approximation to spatially adaptive probability modeling can be used in the solution, as well. With respect to achieving a target rate, the proposed approach and associated fast approximation yield average percentage errors around 0.5% and 1.0% on images in the test set. By comparison, 2-coding-pass rho-domain modeling yields errors around 2.0%, and post-compression rate-distortion optimization yields average errors of around 1.0% at rates below 0.5 bits-per-pixel (bpp) that decrease down to about 0.5% at 1.0 bpp; both methods exhibit more competitive performance on the larger images. The proposed method and fast approximation approach are also similar in speed to the other state-of-the-art methods. In addition to possessing speed and accuracy, the proposed method does not require any training and can maintain precise control over wavelet step sizes, which adds flexibility to a wavelet-based image-coding system. PMID- 17357727 TI - Retaining local image information in gamut mapping algorithms. AB - Our topic is the potential of combining global gamut mapping with spatial methods to retain the percepted local image information in gamut mapping algorithms. The main goal is to recover the original local contrast between neighboring pixels in addition to the usual optimization of preserving lightness, saturation, and global contrast. Special emphasis is placed on avoiding artifacts introduced by the gamut mapping algorithm itself. We present an unsharp masking technique based on an edge-preserving smoothing algorithm allowing to avoid halo artifacts. The good performance of the presented approach is verified by a psycho-visual experiment using newspaper printing as a representative of a small destination gamut application. Furthermore, the improved mapping properties are documented with local mapping histograms. PMID- 17357728 TI - Multiple description image coding based on Lagrangian rate allocation. AB - In this paper, a novel multiple description coding technique is proposed, based on optimal Lagrangian rate allocation. The method assumes the coded data consists of independently coded blocks. Initially, all the blocks are coded at two different rates. Then blocks are split into two subsets with similar rate distortion characteristics; two balanced descriptions are generated by combining code blocks belonging to the two subsets encoded at opposite rates. A theoretical analysis of the approach is carried out, and the optimal rate distortion conditions are worked out. The method is successfully applied to the JPEG 2000 standard and simulation results show a noticeable performance improvement with respect to state-of-the art algorithms. The proposed technique enables easy tuning of the required coding redundancy. Moreover, the generated streams are fully compatible with Part 1 of the standard. PMID- 17357729 TI - A stochastic framework for rate-distortion optimized video coding over error prone networks. AB - This paper proposes a complete stochastic framework for RD optimal encoder design for video over error-prone networks, which applies to any motion-compensated predictive video codec. The distortion measure has been taken as the mean square error over an ensemble of channels given an estimate of the instantaneous packet loss probability. We show that 1) the optimal motion compensated prediction, in the MSE sense, requires computation of the expected value of the reference frames, and 2) calculation of the MSE (distortion measure) requires computation of the second moment of the reference frames. We propose a recursive procedure for the computation of both the expected value and second moment of the reference frames, which are together called the stochastic frame buffer. Furthermore, we propose a stochastic RD optimization method for selection of the optimal macroblock mode and motion vectors given the instantaneous packet loss probability. If available, channel feedback can also be incorporated into the proposed stochastic framework. However, the proposed framework does not require a feedback channel to exist, and when it exists, it does not have to be lossless. In the absence of any packet losses, the proposed stochastic framework reduces to the well-known deterministic RD optimization procedures. One possible application of the optimal stochastic framework would be for multicast streaming to an ensemble of receivers. Experimental results indicate that the proposed framework outperforms other available error tracking and control schemes. PMID- 17357730 TI - Phase unwrapping via graph cuts. AB - Phase unwrapping is the inference of absolute phase from modulo-2pi phase. This paper introduces a new energy minimization framework for phase unwrapping. The considered objective functions are first-order Markov random fields. We provide an exact energy minimization algorithm, whenever the corresponding clique potentials are convex, namely for the phase unwrapping classical Lp norm, with p > or = 1. Its complexity is KT (n, 3n), where K is the length of the absolute phase domain measured in 2pi units and T (n, m) is the complexity of a max-flow computation in a graph with n nodes and m edges. For nonconvex clique potentials, often used owing to their discontinuity preserving ability, we face an NP-hard problem for which we devise an approximate solution. Both algorithms solve integer optimization problems by computing a sequence of binary optimizations, each one solved by graph cut techniques. Accordingly, we name the two algorithms PUMA, for phase unwrappping max-flow/min-cut. A set of experimental results illustrates the effectiveness of the proposed approach and its competitiveness in comparison with state-of-the-art phase unwrapping algorithms. PMID- 17357731 TI - Stochastic view registration of overlapping cameras based on arbitrary motion. AB - A new motion-based method is presented for automatic registration of images in multicamera systems, to permit synthesis of wide-baseline composite views. Unlike existing static-image and motion-based methods, our approach does not need any a priori information about the scene, the appearance of objects in the scene, or their motion. We introduce an entropy-based preselection of motion histories and an iterative Bayesian assignment of corresponding image areas. Finally, correlated point-histories and data-set optimization lead to the matching of the different views. The method is validated by demonstrating its successful use on several real-life indoor and outdoor stereo video image-sequence pairs. PMID- 17357732 TI - Expansion embedding techniques for reversible watermarking. AB - Reversible watermarking enables the embedding of useful information in a host signal without any loss of host information. Tian's difference-expansion technique is a high-capacity, reversible method for data embedding. However, the method suffers from undesirable distortion at low embedding capacities and lack of capacity control due to the need for embedding a location map. We propose a histogram shifting technique as an alternative to embedding the location map. The proposed technique improves the distortion performance at low embedding capacities and mitigates the capacity control problem. We also propose a reversible data-embedding technique called prediction-error expansion. This new technique better exploits the correlation inherent in the neighborhood of a pixel than the difference-expansion scheme. Prediction-error expansion and histogram shifting combine to form an effective method for data embedding. The experimental results for many standard test images show that prediction-error expansion doubles the maximum embedding capacity when compared to difference expansion. There is also a significant improvement in the quality of the watermarked image, especially at moderate embedding capacities. PMID- 17357733 TI - Gait recognition using radon transform and linear discriminant analysis. AB - A new feature extraction process is proposed for gait representation and recognition. The new system is based on the Radon transform of binary silhouettes. For each gait sequence, the transformed silhouettes are used for the computation of a template. The set of all templates is subsequently subjected to linear discriminant analysis and subspace projection. In this manner, each gait sequence is described using a low-dimensional feature vector consisting of selected Radon template coefficients. Given a test feature vector, gait recognition and verification is achieved by appropriately comparing it to feature vectors in a reference gait database. By using the new system on the Gait Challenge database, very considerable improvements in recognition performance are seen in comparison to state-of-the-art methods for gait recognition. PMID- 17357734 TI - Transform coefficient histogram-based image enhancement algorithms using contrast entropy. AB - Many applications of histograms for the purposes of image processing are well known. However, applying this process to the transform domain by way of a transform coefficient histogram has not yet been fully explored. This paper proposes three methods of image enhancement: a) logarithmic transform histogram matching, b) logarithmic transform histogram shifting, and c) logarithmic transform histogram shaping using Gaussian distributions. They are based on the properties of the logarithmic transform domain histogram and histogram equalization. The presented algorithms use the fact that the relationship between stimulus and perception is logarithmic and afford a marriage between enhancement qualities and computational efficiency. A human visual system-based quantitative measurement of image contrast improvement is also defined. This helps choose the best parameters and transform for each enhancement. A number of experimental results are presented to illustrate the performance of the proposed algorithms. PMID- 17357735 TI - Using uncorrupted neighborhoods of the pixels for impulsive noise suppression with ANFIS. AB - In this paper, a novel adaptive network-based fuzzy inference system (ANFIS) based filter, ABF, is presented for the restoration of images corrupted by impulsive noise (IN). The ABF is performed in two steps. In the first step, impulse detection is realized by using statistical tools. In the second step, a nonlinear filtering scheme based on ANFIS is performed for only the corrupted pixels detected in the first step. To demonstrate the effectivity of ABF at the removal of high-level IN, extensive simulations were realized for ABF and nine different comparison filters. Empirical results indicate that the proposed filter achieves a better performance than the comparison filters in terms of noise suppression and detail preservation, even when the images are highly corrupted by IN. PMID- 17357736 TI - Mask design for optical microlithography--an inverse imaging problem. AB - In all imaging systems, the forward process introduces undesirable effects that cause the output signal to be a distorted version of the input. A typical example is of course the blur introduced by the aperture. When the input to such systems can be controlled, prewarping techniques can be employed which consist of systematically modifying the input such that it (at least approximately) cancels out (or compensates for) the process losses. In this paper, we focus on the optical proximity correction mask design problem for "optical microlithography," a process similar to photographic printing used for transferring binary circuit patterns onto silicon wafers. We consider the idealized case of an incoherent imaging system and solve an inverse problem which is an approximation of the real world optical lithography problem. Our algorithm is based on pixel-based mask representation and uses a continuous function formulation. We also employ the regularization framework to control the tone and complexity of the synthesized masks. Finally, we discuss the extension of our framework to coherent and (the more practical) partially coherent imaging systems. PMID- 17357737 TI - Training-based descreening. AB - Conventional halftoning methods employed in electrophotographic printers tend to produce Moire artifacts when used for printing images scanned from printed material, such as books and magazines. We present a novel approach for descreening color scanned documents aimed at providing an efficient solution to the Moire problem in practical imaging devices, including copiers and multifunction printers. The algorithm works by combining two nonlinear image processing techniques, resolution synthesis-based denoising (RSD), and modified smallest univalue segment assimilating nucleus (SUSAN) filtering. The RSD predictor is based on a stochastic image model whose parameters are optimized beforehand in a separate training procedure. Using the optimized parameters, RSD classifies the local window around the current pixel in the scanned image and applies filters optimized for the selected classes. The output of the RSD predictor is treated as a first-order estimate to the descreened image. The modified SUSAN filter uses the output of RSD for performing an edge-preserving smoothing on the raw scanned data and produces the final output of the descreening algorithm. Our method does not require any knowledge of the screening method, such as the screen frequency or dither matrix coefficients, that produced the printed original. The proposed scheme not only suppresses the Moire artifacts, but, in addition, can be trained with intrinsic sharpening for deblurring scanned documents. Finally, once optimized for a periodic clustered dot halftoning method, the same algorithm can be used to inverse halftone scanned images containing stochastic error diffusion halftone noise. PMID- 17357738 TI - Global regularizing flows with topology preservation for active contours and polygons. AB - Active contour and active polygon models have been used widely for image segmentation. In some applications, the topology of the object(s) to be detected from an image is known a priori, despite a complex unknown geometry, and it is important that the active contour or polygon maintain the desired topology. In this work, we construct a novel geometric flow that can be added to image-based evolutions of active contours and polygons in order to preserve the topology of the initial contour or polygon. We emphasize that, unlike other methods for topology preservation, the proposed geometric flow continually adjusts the geometry of the original evolution in a gradual and graceful manner so as to prevent a topology change long before the curve or polygon becomes close to topology change. The flow also serves as a global regularity term for the evolving contour, and has smoothness properties similar to curvature flow. These properties of gradually adjusting the original flow and global regularization prevent geometrical inaccuracies common with simple discrete topology preservation schemes. The proposed topology preserving geometric flow is the gradient flow arising from an energy that is based on electrostatic principles. The evolution of a single point on the contour depends on all other points of the contour, which is different from traditional curve evolutions in the computer vision literature. PMID- 17357739 TI - Foveated visual search for corners. AB - We cast the problem of corner detection as a corner search process. We develop principles of foveated visual search and automated fixation selection to accomplish the corner search, supplying a case study of both foveated search and foveated feature detection. The result is a new algorithm for finding corners, which is also a corner-based algorithm for aiming computed foveated visual fixations. In the algorithm, long saccades move the fovea to previously unexplored areas of the image, while short saccades improve the accuracy of putative corner locations. The system is tested on two natural scenes. As an interesting comparison study, we compare fixations generated by the algorithm with those of subjects viewing the same images, whose eye movements are being recorded by an eye tracker. The comparison of fixation patterns is made using an information-theoretic measure. Results show that the algorithm is a good locater of corners, but does not correlate particularly well with human visual fixations. PMID- 17357740 TI - Combining Monte Carlo and mean-field-like methods for inference in hidden Markov random fields. AB - Issues involving missing data are typical settings where exact inference is not tractable as soon as nontrivial interactions occur between the missing variables. Approximations are required, and most of them are based either on simulation methods or on deterministic variational methods. While variational methods provide fast and reasonable approximate estimates in many scenarios, simulation methods offer more consideration of important theoretical issues such as accuracy of the approximation and convergence of the algorithms but at a much higher computational cost. In this work, we propose a new class of algorithms that combine the main features and advantages of both simulation and deterministic methods and consider applications to inference in hidden Markov random fields (HMRFs). These algorithms can be viewed as stochastic perturbations of variational expectation maximization (VEM) algorithms, which are not tractable for HMRF. We focus more specifically on one of these perturbations and we prove their (almost sure) convergence to the same limit set as the limit set of VEM. In addition, experiments on synthetic and real-world images show that the algorithm performance is very close and sometimes better than that of other existing simulation-based and variational EM-like algorithms. PMID- 17357741 TI - Adaptive Rao-Blackwellized particle filter and its evaluation for tracking in surveillance. AB - Particle filters can become quite inefficient when being applied to a high dimensional state space since a prohibitively large number of samples may be required to approximate the underlying density functions with desired accuracy. In this paper, by proposing an adaptive Rao-Blackwellized particle filter for tracking in surveillance, we show how to exploit the analytical relationship among state variables to improve the efficiency and accuracy of a regular particle filter. Essentially, the distributions of the linear variables are updated analytically using a Kalman filter which is associated with each particle in a particle filtering framework. Experiments and detailed performance analysis using both simulated data and real video sequences reveal that the proposed method results in more accurate tracking than a regular particle filter. PMID- 17357742 TI - Vehicle detection using normalized color and edge map. AB - This paper presents a novel vehicle detection approach for detecting vehicles from static images using color and edges. Different from traditional methods, which use motion features to detect vehicles, this method introduces a new color transform model to find important "vehicle color" for quickly locating possible vehicle candidates. Since vehicles have various colors under different weather and lighting conditions, seldom works were proposed for the detection of vehicles using colors. The proposed new color transform model has excellent capabilities to identify vehicle pixels from background, even though the pixels are lighted under varying illuminations. After finding possible vehicle candidates, three important features, including corners, edge maps, and coefficients of wavelet transforms, are used for constructing a cascade multichannel classifier. According to this classifier, an effective scanning can be performed to verify all possible candidates quickly. The scanning process can be quickly achieved because most background pixels are eliminated in advance by the color feature. Experimental results show that the integration of global color features and local edge features is powerful in the detection of vehicles. The average accuracy rate of vehicle detection is 94.9%. PMID- 17357743 TI - Ant colony optimization for image regularization based on a nonstationary Markov modeling. AB - Ant colony optimization (ACO) has been proposed as a promising tool for regularization in image classification. The algorithm is applied here in a different way than the classical transposition of the graph color affectation problem. The ants collect information through the image, from one pixel to the others. The choice of the path is a function of the pixel label, favoring paths within the same image segment. We show that this corresponds to an automatic adaptation of the neighborhood to the segment form, and that it outperforms the fixed-form neighborhood used in classical Markov random field regularization techniques. The performance of this new approach is illustrated on a simulated image and on actual remote sensing images. PMID- 17357744 TI - Real-time stereo matching using orthogonal reliability-based dynamic programming. AB - A novel algorithm is presented in this paper for estimating reliable stereo matches in real time. Based on the dynamic programming-based technique we previously proposed, the new algorithm can generate semi-dense disparity maps using as few as two dynamic programming passes. The iterative best path tracing process used in traditional dynamic programming is replaced by a local minimum searching process, making the algorithm suitable for parallel execution. Most computations are implemented on programmable graphics hardware, which improves the processing speed and makes real-time estimation possible. The experiments on the four new Middlebury stereo datasets show that, on an ATI Radeon X800 card, the presented algorithm can produce reliable matches for 60% approximately 80% of pixels at the rate of 10 approximately 20 frames per second. If needed, the algorithm can be configured for generating full density disparity maps. PMID- 17357745 TI - Endangered species. PMID- 17357746 TI - Danse macabre. Poverty, social status, and health. PMID- 17357747 TI - Six decades of progress and change in hospital medicine, 1947-2007. PMID- 17357748 TI - Saturday night in Mariposa. PMID- 17357749 TI - Cole Porter's orthopaedic odyssey. PMID- 17357750 TI - Trauma on trauma. Lessons from the tsunami and civil conflict in Sri Lanka. PMID- 17357751 TI - Knowing my body. PMID- 17357752 TI - Matching blindness elimination efforts to health- seeking behavior. PMID- 17357753 TI - The tradition of the gold-headed cane. PMID- 17357754 TI - Of hospital advertising truths, half truths, and the academic medical center. PMID- 17357755 TI - Of truths, half truths, and less than half truths on the road to health. PMID- 17357756 TI - Professionalism. PMID- 17357757 TI - Re donuts. PMID- 17357758 TI - Re doctorspeak. PMID- 17357759 TI - Should residents deploy? PMID- 17357760 TI - The validity of self-reported physical fitness test scores. AB - Epidemiological studies often have to rely on a participant's self-reporting of information. The validity of the self-report instrument is an important consideration in any study. The purpose of this investigation was to determine the validity of self-reported Army Physical Fitness Test (APFT) scores. The APFT is administered to all soldiers in the U.S. Army twice a year and consists of the maximum number of push-ups completed in 2 minutes, the maximum number of sit-ups completed in 2 minutes, and a 2-mile run for time. Army mechanics responded to a questionnaire in March and June 2004 asking them to report the exact scores of each event on their most recent APFT. Actual APFT scores were obtained from the soldier's military unit. The mean +/- standard deviation (SD) of actual and self reported numbers of push-ups was 61 +/- 14 and 65 +/- 13, respectively. The mean +/- SD of actual and self-reported numbers of sit-ups were 66 +/- 10 and 68 +/- 10, respectively. The mean +/- SD of actual and self-reported run times (minutes) were 14.8 +/- 1.4 and 14.6 +/- 1.4, respectively. Correlations between actual and self-reported push-ups, sit-ups, and run were 0.83, 0.71, and 0.85, respectively. On average, soldiers tended to slightly over-report performance on all APFT events and individual self-reported scores could vary widely from actual scores based on Bland-Altman plots. Despite this, the close correlations between the actual and self-reported scores suggest that self-reported values are adequate for most epidemiological military studies involving larger sample sizes. PMID- 17357761 TI - Physical fitness, training volume, and self-determined motivation in soldiers during a peacekeeping mission. AB - PURPOSE: The goal was to register physical training volume and to measure changes in physical fitness in soldiers during a peacekeeping mission. The relationship between these factors and motivation for physical training was also investigated. METHODS: Physical training volume was registered and maximal oxygen uptake, 3-km run time, sit-ups, push-ups, and chin-ups were tested before and after 1 year of service for 71 Norwegian soldiers in the international Kosovo Force. Self determined motivation was measured at the end of the service. RESULTS: Physical training volume was 117 +/- 77 minutes/week. The average maximal oxygen uptake decreased by 2.5 +/- 0.8% (p < 0.01). Intrinsic motivation positively predicted physical training volume (p < 0.01). CONCLUSIONS: A large variation in training volume was found, and only one-third of the soldiers improved physical fitness and maintained body weight. Fostering intrinsic motivation toward physical training is key to increasing training volume. However, obligatory training could ensure a minimum of physical training among the soldiers who were least motivated for physical training. PMID- 17357762 TI - Experiences of medical care with the 250th Forward Surgical Team (Airborne) during a military operation into Northern Iraq in 2003. PMID- 17357763 TI - Cold and heat strain during cold-weather field training with nuclear, biological, and chemical protective clothing. AB - The objective of this study was to quantify the thermal strain of soldiers wearing nuclear, biological, and chemical protective clothing during short-term field training in cold conditions. Eleven male subjects performed marching exercises at moderate and heavy activity levels for 60 minutes. Rectal temperature (Tre), skin temperatures, and heart rate were monitored. Ambient temperature (Ta) varied from -33 to 0 degrees C. Tre was affected by changes in metabolism, rather than in Ta. Tre increased above 38 degrees during heavy exercise even at -33 degrees C. The mean skin temperature decreased to tolerance level (25 degrees C) at Ta below -25 degrees C with moderate exercise. Finger temperature decreased below 15 degrees C (performance degradation) at Ta of -15 degrees C or cooler. The present results from the field confirm the previous results based on laboratory studies and show that risk of both heat and cold strain is evident, with cooling of extremities being most critical, while wearing nuclear, biological, and chemical protective clothing during cold-weather training. PMID- 17357764 TI - Effects of acclimation on cognitive performance in soldiers during exertional heat stress. AB - This study investigates the effects of exertional heat stress and acclimation status on physiological and cognitive performance. Forty male soldiers performed an exertional heat stress test (EHST) either in a cool (20 degrees C, 16 degrees C wet bulb globe temperature), or in a hot environment (40 degrees C, 29 degrees C wet bulb globe temperature), unacclimatized, or after 10 days of passive or active acclimation. Mean skin and tympanic (Tty) temperatures and heart rates (HR) measured physiological strain. A cognitive test (the computerized Cambridge Neuropsychological Test Automated Batteries attention battery) is administered before and immediately after EHST. EHST in hot conditions induced physiological heat stress (increase in Tty and HR), which caused mild deficits in attention in U group (decreased number of correct responses, and prolonged movement time). Acclimated (passive and active) soldiers suffered no detrimental effects of exertional heat stress, despite almost the same degree of heat strain, measured by Tty and HR. PMID- 17357765 TI - Helicobacter pylori infection and seasickness susceptibility among naval sailors: is there any association? AB - BACKGROUND: Vomiting is a very common and bothersome expression of seasickness. Previous works have shown that Helicobacter pylori infection may be related to vomiting resulting from nongastrointestinal causes, and physiological research has revealed that H. pylori may alter gastric motility. These findings, along with anecdotal case histories, led us to suspect that H. pylori infection may be related to the vomiting of seasickness. The objective of this study was to evaluate the association between H. pylori infection and seasickness susceptibility. METHODS: Participants were 90 healthy, male, naval crew members 19.5 to 25 years of age. Forty-five were susceptible to seasickness, and 45 were nonsusceptible control subjects. Quantitative analysis of IgG levels for H. pylori was performed with an enzyme-linked immunosorbent assay. RESULTS: The rate of H. pylori infection was 38% in the susceptible group, compared with 31% in the nonsusceptible group (p = 0.5). The titer of antibodies to H. pylori among case subjects was 81.2 U/mL (95% confidence interval, 11.5-151.1 U/mL), compared with 31.1 U/mL (95% confidence interval, 0.1-65.1 U/mL) for control subjects (p = 0.2). CONCLUSION: The current study does not support an association between H. pylori infection and seasickness susceptibility among sailors. PMID- 17357766 TI - Stress management and factors related to the deployment of Italian peacekeepers in Afghanistan. AB - This cross-sectional study evaluated the stress levels in Italian military personnel involved in a peacekeeping (PK) mission in Afghanistan and a homogeneous group stationed in Italy (SI group). The study was performed from April 2004 to June 2004 in a sample of 160 long-time, career volunteers of the Rossi Barracks of the Alpini di L'Aquila (Italy) (SI group, n=120; PK group, n=40). A 10-item, self-evaluation questionnaire proposed in the U.N. Stress Management Booklet was administered to each volunteer. The total item score (TIS) values for the 10 items for the two groups were calculated. These values were greater for the PK group than for the SI group for all 10 items. The TIS values were grouped into three classes of symptoms, anxiety symptoms (items 1-4), stress induced depression (items 5-7), and posttraumatic stress (items 8-10). The class total item score (CTIS) values were then calculated as the sum of the respective TIS values. The three CTIS values for the PK group were greater than those for the SI group. In particular, the anxiety CTIS was 72 points greater in the PK group (p < 0.001). Therefore, the peacekeepers were inclined to have a greater increase in anxiety symptoms. Consequently, antipanic techniques could be used to reduce anxiety and progressive muscular relaxation training, an important preventive relaxation technique, to face stressors and to reduce clinical anxiety. PMID- 17357767 TI - Latent schistosomiasis in Portuguese soldiers. AB - Schistosomiasis was diagnosed in two Portuguese soldiers who had been deployed to Portuguese colonies in Africa. The first veteran was diagnosed as having schistosomiasis 34 years after returning from Angola, and the second veteran was found with Schistosoma haematobium infection 40 years after returning from Mozambique. The patient with Schistosoma mansoni had an active infection, because eggs were recovered with living miracidia. The second patient had developed urothelial cancer, but eggs recovered were calcified. PMID- 17357768 TI - Disordered eating in entry-level military personnel. AB - OBJECTIVE: The goal was to determine the prevalence of and risk factors for disordered eating in an entry-level U.S. Army population. METHODS: A cross sectional survey of advanced individual training U.S. Army soldiers at Aberdeen Proving Ground, Maryland, was performed with an anonymous self-report survey containing demographic factors, history (including abuse and psychiatric treatment), and Eating Attitudes Test-26. RESULTS: Of 1,184 advanced individual training soldiers approached, 1090 participated. The response rate was 91.2% (955 men and 135 women). Forty percent were overweight (body mass index of > or =25), 11% reported a psychiatric history, 26% reported a history of abuse, and 9.8% endorsed disordered eating (male, 7.0%; female, 29.6%), as defined by Eating Attitudes Test-26. Factors that placed soldiers at higher risk for disordered eating were female gender (odds ratio, 5.63; 95% confidence interval, 3.32-9.57; p < 0.00005), overweight (odds ratio, 3.06; 95% confidence interval, 1.92-4.89; p < 0.00005), previous psychiatric treatment (odds ratio, 1.87; 95% confidence interval, 1.04-3.36; p = 0.035), and history of verbal abuse (odds ratio, 2.02; 95% confidence interval, 1.16-3.51; p = 0.014). CONCLUSIONS: Our study shows a higher than expected rate of disordered eating in advanced individual training soldiers with identifiable risk factors. This indicates an important need for further study, effective screening, preventive counseling, and early intervention for treatment. PMID- 17357769 TI - Eating and body attitudes related to noncompetitive bodybuilding in military and general Hungarian male student populations. AB - Pathological eating attitudes and extreme weight control practices occur most commonly in certain female populations. In some young male occupation groups, such as in the armed forces, the appearance of physical strength and muscularity has particular importance. We studied body and eating attitudes and the prevalence of bodybuilding and steroid abuse in 480 military college and 752 general college male students. The Eating Disorder Inventory was used for all subjects. General college students had higher body mass index values than did military students. The prevalence of bodybuilding and steroid abuse was significantly greater in the military population. Comparisons between the study groups and within groups showed significantly different scores on certain Eating Disorder Inventory subscales. The study revealed that male military college students have some protective factors against the psychopathological features of eating disorders. PMID- 17357770 TI - The stigma of mental health problems in the military. AB - The present review addresses the perceived stigma associated with admitting a mental health problem and seeking help for that problem in the military. Evidence regarding the public stigma associated with mental disorders is reviewed, indicating that the public generally holds negative stereotypes toward individuals with psychological problems, leading to potential discrimination toward these individuals. The internalization of these negative beliefs results in self-stigma, leading to reduced self-esteem and motivation to seek help. Even if soldiers form an intention to seek help for their psychological difficulty, barriers to mental health care may prevent the soldier from receiving the help they need. An overall model is proposed to illustrate how the stigma associated with psychological problems can prevent soldiers getting needed help for psychological difficulties and proposed interventions for reducing stigma in a civilian context are considered for military personnel. PMID- 17357771 TI - Compensation of veterans with psychiatric or substance abuse disorders and employment and earnings. AB - Using a national sample of veterans, we examined the relationship between disability income and employment, adjusting for health status and other factors. Veterans Affairs disability income payments had no globally detrimental effect on labor force participation, in that the likelihood of employment was reduced only at payment levels of more than $800 per month. Although unearned income from other sources also did not have a substantial negative effect on labor force participation, veterans who received benefits from the Social Security Administration or welfare payments were less likely to be employed, mostly likely because employment earnings above a certain level in some programs may result in the loss of monetary benefits and health insurance. PMID- 17357772 TI - Efficacy of group cognitive behavior therapy for the treatment of masticatory myofascial pain. AB - The purpose of this investigation was to evaluate the reduction in perceived pain in patients with myofascial pain (MFP) using a group cognitive behavior therapy (CBT) course. Twenty-six participants diagnosed as having MFP were enrolled. Each CBT session had a small-group format, where participants received instruction in habit reversal, stress management, and progressive relaxation. Participants served as their own control subjects and were surveyed for pain intensity, duration, and frequency at study enrollment, before attending the CBT course, and 2 to 3 weeks after course completion. Wilcoxon signed-rank tests revealed that changes in intensity, frequency, and duration were significant (p < 0.001 to p < 0.045). Thirty-three percent of the participants showed improvement with home care instructions before CBT course start, whereas 65% of the participants showed improvement after the CBT course. Participants attending CBT group training exhibited significant improvements in MFP intensity, frequency, and duration, compared with levels reported at the initial evaluation. PMID- 17357773 TI - Abuse of war zone detainees: veterans' perceptions of acceptability. AB - We assessed detainee abuse acceptance and variables associated with it. Outpatients from a veterans' hospital were administered questionnaires with three increasingly severe scenarios of a U.S. soldier abusing a detainee. Three questionnaire versions differed in the final line of each version's scenarios, describing abuse either as: soldier initiated, superior ordered, or wrong by a "whistleblower" soldier. Three hundred fifty-one veterans participated, 80% with service during the Vietnam War. Zero tolerance for abuse--"completely unacceptable" regardless of who the detainee was--increased with abuse severity (16% for exposure, 31% for humiliation, and 48% for rape of detainee) and with soldier initiation. The strongest, most consistently significant odds were of depressed veterans, veterans with comorbid depression/post-traumatic stress disorder, and men being approximately 2, 3, and 4 to 20 times more tolerant of abuse than those without depression/post-traumatic stress disorder and women, respectively. There may be potential value to using similar scenario-based questionnaires to study active duty military perceptions of detainee abuse. Results may inform prevention policies. PMID- 17357774 TI - High-intensity acoustics for military nonlethal applications: a lack of useful systems. AB - There have been many previous claims of nonlethal acoustic weapon effects, mostly in the popular rather than the scientific literature. Anecdotal reports of extraordinary effects can make meaningful assessment and review of this area very difficult. Acoustics research has shown that the nonlethal weapon capabilities of audible sound generators have been grossly overstated. Although high-intensity infrasound significantly disrupted animal behavior in some experiments, the generation of such energy in a volume large enough to be of practical use is unlikely because of basic physical principles. On the basis of experimentation completed to date at a number of institutions, it seems unlikely that high intensity acoustic energy in the audible, infrasonic, or low-frequency range can provide a device suitable for use as a nonlethal weapon. PMID- 17357775 TI - Immune cytokine response in combat casualties: blast or explosive trauma with or without secondary sepsis. AB - The aim of this study was to assess the prognostic value of tumor necrosis factor (TNF) alpha, interleukin (IL)-8, IL-4, and IL-10 in combat casualties. Fifty-six casualties with severe trauma (blast and explosive) who developed sepsis and 20 casualties with the same severity of trauma without sepsis were enrolled in this study. Fifty-five casualties developed multiple organ dysfunction syndrome; 36 died. Blood was drawn on the first day of trauma. Concentrations of IL-8, TNF alpha, IL-4, and IL-10 were determined in plasma using enzyme-linked immunosorbent assays. Mean values of IL-8 were 230-fold, IL-10 were 42-fold, and TNF-alpha were 17-fold higher in trauma and sepsis group (p < 0.01). Mean values of IL-8 were 60-fold, TNF-alpha were 43.5-fold, and IL-10 were 70-fold higher in the multiple organ dysfunction syndrome group (p < 0.01). Mean values of IL-8 were 2.3-fold and IL-10 were 1.4-fold higher in nonsurvivors and TNF-alpha were 2.2-fold higher in survivors (p < 0.01). IL-4 had no significance as a predictor of severity and outcome. PMID- 17357776 TI - Liquid sulfur mustard exposure. AB - A 35-year-old active duty service member sustained a 6.5% body surface area burn as a result of exposure to the chemical warfare agent sulfur mustard, which is the most severe mustard exposure of a U.S. military member since World War II that is known to us. New techniques were used to demonstrate the detectable persistence of mustard metabolites in the patient's blood for at least 41 days after exposure, validating these techniques for the first time for a human mustard patient; they were also used for the first time with human mustard blister fluid. The techniques extend eightfold the period of time that mustard exposure can be definitively diagnosed, compared with previous techniques. Although this patient's lesions were never life-threatening, he required 2 weeks of intensive burn care. He has been left with ongoing posttraumatic stress disorder and has had an incomplete dermatological recovery. In a major terrorist attack involving many patients exposed to sulfur mustard, care resources would be depleted quickly. PMID- 17357777 TI - The 81st Medical Group obstetrics and gynecology flight's role during Hurricane Katrina. AB - BACKGROUND: The Obstetrics and Gynecology (OB/GYN) flight at Keesler Medical Center sheltered 36 pregnant women and their families during Hurricane Katrina to ensure that appropriate medical care would be available. Ironically, the hospital's emergency generators were destroyed during the 30-foot storm surge, while one woman with a previous cesarean section went into active labor. She ultimately underwent a cesarean delivery using battery-operated flashlights for illumination. After the storm, the damage to the hospital was so extensive as to require aeromedical evacuation of the pregnant patients and their families. In addition, two OB/GYN physicians transferred to a nearby shelter on base and provided general medical care to its occupants. CONCLUSION: OB/GYN physicians in the military play a vital role in the care of victims of natural disasters. In addition to pregnancy-related issues, OB/GYN physicians can be expected to provide primary and emergency care to victims under austere conditions. PMID- 17357778 TI - Establishing institutional critical values of follicle-stimulating hormone levels to predict in vitro fertilization success. AB - Elevated follicle-stimulating hormone (FSH) levels during the early follicular phase or in response to the clomiphene citrate challenge test indicate diminished ovarian reserve and poor reproductive potential. We performed a retrospective analysis of 413 infertile women, 23 to 40 years of age, who underwent 523 cycles of in vitro fertilization (IVF) to identify the critical FSH values that would predict a poor likelihood of success in our military IVF program. Each woman underwent a clomiphene citrate challenge test within 1 year of each IVF cycle. The overall live birth and implantation rates were 43% and 24%, respectively. The critical values for day 3 and day 10 FSH levels were 14.1 and 16.9 mIU/mL, respectively, with a 0% live birth rate and a 5% implantation rate above these levels. There were no differences in the live birth/implantation rates when stratified for FSH levels below the critical values. Medical centers offering IVF should determine their critical FSH values, to help identify patients unlikely to benefit from IVF and to ensure appropriate allocation of resources and realistic expectations for infertile couples. PMID- 17357779 TI - An innovative medical civil-military operation training program. AB - The San Antonio Military Pediatric Center has developed an innovative humanitarian civic assistance (HCA) program. Many medical HCA programs focus on short-term medical interventions and provide transient benefit. To have a more lasting impact, this program focuses on public health surveillance. U.S. military medics conduct random household nutritional surveys and train in austere settings and on rounds in Honduran hospitals. Since 2001, >200 military medics have been trained in population assessment, primary medical care in developing nations, and other skills critical for medical civil-military operations. All activities are coordinated with the host nation. Public health data are collected and reported to Honduran public health leaders, the U.S. Agency for International Development, and nongovernmental organizations, to assist with program and policy development. This innovative project is a potential model to improve both military training and host nation benefit from HCA programs. PMID- 17357780 TI - Do residents benefit from participating in internal medicine interest groups? A study of resident perceptions from two institutions. AB - BACKGROUND: For more than a decade, primary care residency training programs have struggled to attract graduates of U.S. medical schools. Internal medicine (IM) interest groups (IMIGs) have been widely instituted to foster student interest in careers in IM. Residents can participate in many IMIG activities. Studies have not assessed the benefits gained by resident participants in such groups. METHODS: A questionnaire was sent to residents at two IM residency training programs that contribute to IMIG activities at one medical school. Both participating and nonparticipating residents were included. RESULTS: The questionnaire was completed by 44 of 58 IM residents (76% response rate; 25 participants and 19 nonparticipants). Free-text advantages reported were teaching (n=6), mentoring (n=8), and leadership (n=5) opportunities, staying current in IM (n=3), encouraging students to enter IM (n=6), and improving resident morale (n=6). Likert-scale responses were higher for participants than for nonparticipants for all questions; nonparticipants also reported that involvement in IMIG activities is beneficial for residents. Statistically significant results were seen for questions regarding the following: improves resident morale, fosters leadership opportunities, is a valuable experience, and feeling qualified to participate. CONCLUSIONS: Residents perceive that participation in an IMIG confers significant benefit, providing additional justification for conducting these interest groups. PMID- 17357781 TI - A 10-year follow-up of ischemic heart disease risk factors in military pilots. AB - INTRODUCTION: Cardiovascular diseases (CVDs) represent the reason for approximately 10% of all groundings among military pilots. After their first screening examination, which decides their fitness for flight, pilots are required to appear for screening examinations yearly, which makes it possible to monitor the changes in the risk factors of ischemic heart disease (IHD) from their candidate days until their retirement or final grounding. SUBJECTS AND METHODS: During regular fitness screenings, we determined the individual and common occurrence and changes of recorded or measured IHD risk factors on the basis of 10- (baseline), 5-, and 0-year (current) data in the cases of 250 active male military pilots, broken down into 5-year age groups. In addition, by the help of complex risk calculation methods, we calculated the 5- and 10-year risk of coronary artery disease and CVDs, respectively. RESULTS: In the first year of the examinations, the following risk factors appeared: positive family history (25.0%), obesity (40.8%), smoking (31.7%), physical inactivity (23.9%), high blood pressure (14.7%), hypercholesterolemia (53.9%), pathological electrocardiogram deviations (1.3%). By aging, the occurrence of each risk factor remained unchanged or increased and their cumulative occurrence became more frequent, except for those above 45 to 50 yrs, who seldom had four or more risk factors at the same time. The cardiovascular risk calculated by the Futrex program was elevated in 40% of the study population (levels 3 and 4). By aging, the indices received by complex risk calculation methods deteriorated in the age group 25 to 45 years, while they improved in the age group of >45 years. The 5 year risk of CVDs was below 2.5% in half of the study population and it did not exceed 15 to 20% even in the age group with the highest risk. DISCUSSION: Based on reference data, pilots usually represent a healthier population in those countries where coronary artery diseases are leading health problems. In Hungary, many young pilots leave the army due to its currently ongoing transformation, while the elder are less motivated to change careers. It is probably the role of the stricter physical fitness test and screening examinations, and the effect of military propaganda targeting health conservation, that is in the background of the elder pilots' value improvements. It is also an influencing factor that by administering antilipid and antihypertensive medication based on NATO recommendations in the cases of those with increased risk, the probability of the development of IHD decreases and the affected pilots can be kept longer in service. PMID- 17357782 TI - Materials handling ability of regular and reserve British Army soldiers. AB - The main objective of this research was to compare the materials handling ability, aerobic power, and body composition of fully trained Reserve and Regular male British Army soldiers (approximately 6-7 years of military experience). Twenty-one Reserve soldiers and 15 Regular soldiers completed fitness tests, including a maximal box lift to 1.45 m and a repetitive 22-kg box lift-and-carry test. There were no statistically significant differences (p > 0.05) between the two groups in any parameter measured. The performance levels observed in these fully trained soldiers (maximal box lift approximately 63 kg, repetitive lift and carry approximately 34 repetitions) were broadly comparable to those reported previously for new recruits. The physical training performed by the Regular soldiers (both within and beyond their military service) and the Reserve soldiers (predominantly outside their military duties) seems to be of sufficient volume and intensity to maintain performance levels comparable with each other and equivalent new army recruits. PMID- 17357783 TI - Defeating the coding monsters. AB - Accuracy in coding is rapidly becoming a required skill for military health care providers. Clinic staffing, equipment purchase decisions, and even reimbursement will soon be based on the coding data that we provide. Learning the complicated myriad of rules to code accurately can seem overwhelming. However, the majority of clinic visits in a typical outpatient clinic generally fall into two major evaluation and management codes, 99213 and 99214. If health care providers can learn the rules required to code a 99214 visit, then this will provide a 90% solution that can enable them to accurately code the majority of their clinic visits. This article demonstrates a step-by-step method to code a 99214 visit, by viewing each of the three requirements as a monster to be defeated. PMID- 17357784 TI - Radiology corner. Answer to last month's radiology case and images: Schistosomiasis japonicum involving the liver and colon. AB - Abdominal radiography showed subtle curvilinear densities overlying the left lower quadrant and central within the pelvis (Fig. 1a). This was confirmed on intravenous contrast-enhanced abdominopelvic CT to be caused by thin mucosal surface calcifications within the descending and sigmoid colons (Fig. 1b, c). Incidental note is made of thin right hepatic lobe capsule calcifications (Fig. 1d). These colonic and hepatic calcifications are characteristic of Schistosomiasis infection of the gastrointestinal tract. Liver biopsy confirmed Schistosomiasis japonicum infection. PMID- 17357786 TI - Pax-2 and N-myc regulate epithelial cell proliferation and apoptosis in a positive autocrine feedback loop. AB - Both paired homeo box-2 (Pax-2) and N-myc genes play pivotal roles in renal morphogenesis via their effects on cell proliferation and differentiation, but whether and how they interact have not been addressed. In the present study, we investigated such a potential interaction using embryonic renal cells in vitro. Mouse embryonic mesenchymal (MK4) cells stably transfected with Pax-2 cDNA in sense (+) or antisense (-) orientation were used for experiments. Pax-2 promoter activity was monitored by luciferase assay. Reactive oxygen species (ROS) generation, cell proliferation, and cell apoptosis were evaluated. We found that Pax-2 and N-myc gene expression were upregulated and downregulated in Pax-2 (+) and Pax-2 (-) stable transformants, respectively. ROS generation and apoptosis were significantly reduced both in Pax-2 (+) transformants compared with Pax-2 ( ) transformants and in naive MK4 cells cultured in either normal- (5 mM) or high glucose (25 mM) medium. Transient transfection of N-myc cDNA into Pax-2 (-) stable transformants restored Pax-2 gene expression and prevented ROS generation induced by high glucose. Our data demonstrate that Pax-2 gene overexpression prevents hyperglycemia-induced apoptosis, and N-myc appears to provide a positive autocrine feedback on Pax-2 gene expression in embryonic mesenchymal cells. PMID- 17357785 TI - What's new in the aetiopathogenesis of vasculitis? AB - The cause of the majority of childhood vasculitides is unknown although it is likely that a complex interaction between environmental factors and inherited host responses trigger the disease and determine the vasculitis phenotype. Epidemiological clues continue to implicate infectious triggers in Kawasaki syndrome (KS) and Henoch Schonlein purpura (HSP). Several genetic polymorphisms have now been described in KS and HSP which predispose to disease or predict disease severity. Anti-neutrophil cytoplasmic antibodies (ANCA) are now known to be directly involved in the pathogenesis of vascular injury in ANCA-associated vasculitides, although why some individuals develop ANCA in the first instance is not yet understood. Endothelial injury and repair are active areas of research in vasculitis. It is now possible to track endothelial injury non-invasively in children with vasculitis using surrogate markers of endothelial injury. The vasculogenic pathways involved in vascular repair following vasculitis, including endothelial progenitor cells, are beginning to be studied. It is anticipated that an improved understanding of the aetiopathogenesis of vasculitis in the young will ultimately shape future novel diagnostic and therapeutic approaches and will help us predict which children may develop premature arteriosclerosis in later life. PMID- 17357788 TI - ["Let the cobbler stick to his last"]. PMID- 17357787 TI - Bardet-Biedl syndrome: beyond the cilium. AB - The Bardet-Biedl syndrome (BBS) is a significant genetic cause of chronic and end stage renal failure in children. Despite being a relatively rare recessive condition, BBS has come to prominence during the past few years owing to revelations of primary cilia dysfunction underlying pathogenesis. The study of this multi-system disorder, which includes obesity, cognitive impairment, genito urinary tract malformations and limb deformities, is beginning to reveal insights into several aspects of mammalian development and organogenesis. Involvement of BBS proteins in disparate pathways such as the non-canonical Wnt and Sonic Hedgehog pathways is highlighting their interplay in disease pathogenesis. Here we review the recent developments in this emerging field, with the emphasis on the renal component of the syndrome and potential future directions. PMID- 17357789 TI - [Arteriovenous malformation of the mandible: life-threatening manifestation during tooth extraction]. AB - CASE REPORT: We report on the case of a 31-year old female presenting a massive bleeding during extraction of left lower wisdom tooth, which could be managed by local compression. In the following transfemoral angiography an extensive arteriovenous malformation (avm) in the pterygomandibular space with osseous infiltration was diagnosed and embolised during the same session. After the acute stage the malformation could be controlled by repeated embolisation, the wound being closed by use of a transposition flap. CONCLUSIONS: Although arteriovenous malformations of the head and neck are rare, they can manifest with dramatic bleeding complications during surgical interventions. A thrill on palpation and auscultation may also refer to the existence of such a vascular lesion. An av malformation may be stimulated by hormonal changes during puberty or pregnancy as well as by local trauma. Colour coded duplex sonography, magnetic resonance imaging and transfemoral angiography are suitable diagnostic tools. The treatment of choice is superselective embolisation followed by surgical resection of the vascular nidus, which should be performed by under an interdisciplinary approach. PMID- 17357790 TI - Time-dependent changes in pulmonary vascular responses to acute hypoxia during and after cold exposure in rats. AB - This study evaluated time-dependent alterations in pulmonary vascular reactivity to acute hypoxia and to the administration of angiotensin II (AT-II) during and after chronic exposure to cold using isolated perfused lung specimens from rats. Animals were exposed to a cold environment (3.5 (mean) +/- 1.0 (SD) degrees C) or to a normal temperature (24.0 +/- 1.0 degrees C) for 7 days. The isolated lungs were taken serially and pulmonary vascular responses to acute hypoxia and AT-II were examined. Both the pulmonary vascular responses to acute hypoxia and to AT II were significantly reduced 9 h after the exposure to cold. The diminished vascular response to AT-II was restored to the pre-exposure level after 5 days of cold exposure and then sustained. On the other hand, the reduced response to acute hypoxia was sustained for the first 7 days during exposure to cold and then returned to the pre-exposure level during sustained exposure to cold. After removal from the 7 days of cold exposure, the pulmonary vascular response to acute hypoxia was immediately restored. Thus, during exposure to cold, pulmonary vascular response to acute hypoxia was more sustained than the AT-II-induced vasoconstriction. We concluded that cold exposure alters pulmonary vascular responses to acute hypoxia and AT-II in rats, but that the response to acute hypoxia is more sustained than that of AT-II. PMID- 17357791 TI - Quiet stance control is affected by prior treadmill but not overground locomotion. AB - Treadmill locomotion is different with respect to overground walking and may require an adapted control mode. The relevant neural computational effort may produce lasting effects encroaching upon the performance of a subsequent postural task. The hypothesis of the present study was that, contrary to overground walking, treadmill walking has effects on quiet stance variables, in the assumption that the imposed locomotor activity is more critical to stance control than natural walking. Nine young subjects performed three different walking sessions: treadmill with eyes closed, treadmill with eyes open, overground walking with eyes open. Body sway area and sway path and the position of the centre of foot pressure during stance were recorded by a dynamometric platform under control, post-walking and post-recovery conditions, alternatively with eyes closed and eyes open. At variance with overground walking, treadmill locomotion produced an effect on body orientation in space during the subsequent stance trials. This consisted in a forward inclination of the body, not accompanied by increased body sway, lasting for a few minutes. Presence or absence of vision during treadmill locomotion did not induce differences in the amplitude or time course of the post-effect. We argue that body inclination would be the consequence of a change in the postural reference produced by a message arising from treadmill locomotion itself, possibly connected to particularities in the control mode of this type of walking. PMID- 17357792 TI - The effect of exercise type on immunofunctional and traditional growth hormone. AB - The purpose of this study was to compare the growth hormone (GH) response, including the immunfunctional (IF) GH response, between an acute bout of aerobic and resistance exercise in the same subjects. Ten cross-trained males (24.3 +/- 1.2 years) performed both 30 min of continuous cycling at 70% of VO(2max), and intermittent free weight squatting at 70% of 1-RM, in a randomly assigned crossover design, separated by at least 1 week. Blood samples were collected at 10-min intervals for 2 h (30 min rest, 30 min exercise, 60 min recovery) and analyzed for total human and IF GH. After adjusting for the amount of work performed per minute of exercise, integrated GH AUC was significantly greater during the resistance session than the aerobic session as measured by both the total and IF GH assays (P = 0.008 and P = 0.014, respectively). Peak GH concentrations were significantly greater during the resistance session than the aerobic session (P = 0.05). A similar overall GH pattern was observed in response to both types of exercise, with peak values occurring at the end of exercise, regardless of the GH assay used. These data demonstrate that in young, cross trained males, intermittent resistance exercise elicits a greater response of GH, including IF GH, compared to a continuous aerobic session, when controlling for the work performed per minute, intersubject variability, relative exercise intensity and session duration. PMID- 17357793 TI - Conventionally assessed voluntary activation does not represent relative voluntary torque production. AB - The ability to voluntarily activate a muscle is commonly assessed by some variant of the twitch interpolation technique (ITT), which assumes that the stimulated force increment decreases linearly as voluntary force increases. In the present study, subjects (n = 7) with exceptional ability for maximal voluntary activation (VA) of the knee extensors were used to study the relationship between superimposed and voluntary torque. This includes very high contraction intensities (90-100%VA), which are difficult to consistently obtain in regular healthy subjects (VA of approximately 90%). Subjects were tested at 30, 60, and 90 degrees knee angles on two experimental days. At each angle, isometric knee extensions were performed with supramaximal superimposed nerve stimulation (triplet: three pulses at 300 Hz). Surface EMG signals were obtained from rectus femoris, vastus lateralis, and medialis muscles. Maximal VA was similar and very high across knee angles: 97 +/- 2.3% (mean +/- SD). At high contraction intensities, the increase in voluntary torque was far greater than would be expected based on the decrement of superimposed torque. When voluntary torque increased from 79.6 +/- 6.1 to 100%MVC, superimposed torque decreased from 8.5 +/ 2.6 to 2.8 +/- 2.3% of resting triplet. Therefore, an increase in VA of 5.7% (from 91.5 +/- 2.6 to 97 +/- 2.3%) coincided with a much larger increase in voluntary torque (20.4 +/- 6.1%MVC) and EMG (33.9 +/- 6.6%max). Moreover, a conventionally assessed VA of 91.5 +/- 2.6% represented a voluntary torque of only 79.6 +/- 6.1%MVC. In conclusion, when maximal VA is calculated to be approximately 90% (as in regular healthy subjects), this probably represents a considerable overestimation of the subjects' ability to maximally drive their quadriceps muscles. PMID- 17357794 TI - The last 3 days of life in three different care settings in The Netherlands. AB - INTRODUCTION: Little is known about the characteristics of dying in different care settings, such as the hospital, the nursing home, or the home-care setting. MATERIALS AND METHODS: We measured the burden of symptoms, medical and nursing interventions, and aspects of communication during the last 3 days of life within each of these settings. We included 239 of 321 patients (74%) who died in one of these settings in the southwest of The Netherlands, between November 2003 and February 2005. After the patient's death, a nurse filled in a questionnaire. RESULTS: Pain and shortness of breath were more severe in hospital patients as compared to nursing home and home-care patients, whereas incontinence was less severe in hospital patients. Several medical interventions, such as a syringe driver, vena punctures or lab tests, radiology or ECG, antibiotics, and drainage of body fluids were more often applied during the last 3 days of life to hospital patients than to nursing home and home-care patients. This also holds for the measurement of body temperature and blood pressure. In the hospital setting, the patient and the family were more often informed about the imminence of death of the patient than elsewhere. The general practitioner and other professional caregivers were less often informed about the imminence of death of hospital patients than of other patients. DISCUSSION: We conclude that pain and shortness of breath were more severe among hospital patients, whereas incontinence was more severe among nursing home and home-care patients. Hospital patients relatively often receive medical interventions and standard controls during the last 3 days of life. In hospital, communication about impending death seems to take place more often shortly before death. PMID- 17357795 TI - The integration of familiarity and recollection information in short-term recognition: modeling speed-accuracy trade-off functions. AB - Dual process models postulate familiarity and recollection as the basis of the recognition process. We investigated the time-course of integration of the two information sources to one recognition judgment in a working memory task. We tested 24 subjects with a response signal variant of the modified Sternberg recognition task (Oberauer, 2001) to isolate the time course of three different probe types indicating different combinations of familiarity and source information. We compared two mathematical models implementing different ways of integrating familiarity and recollection. Within each model, we tested three assumptions about the nature of the familiarity signal, with familiarity having (a) only positive values, indicating similarity of the probe with the memory list, (b) only negative values, indicating novelty, or (c) both positive and negative values. Both models provided good fits to the data. A model combining the outputs of both processes additively (Integration Model) gave an overall better fit to the data than a model based on a continuous familiarity signal and a probabilistic all-or-none recollection process (Dominance Model). PMID- 17357796 TI - Association between personal exposure to volatile organic compounds and asthma among US adult population. AB - OBJECTIVES: There is growing concern about adverse respiratory health effects from exposure to indoor air pollution. The purpose of this study was to analyze association between exposure to volatile organic compounds (VOC) and asthma in adults. METHODS: This study utilized passive personal exposure data on ten VOC collected as part of the National Health and Nutrition Examination Survey (NHANES) 1999-2000. A total of 550 subjects who were of non-Hispanic whites, Mexican-Americans, or non-Hispanic Blacks race/ethnicity were included in this analysis. The primary outcome variable was physician-diagnosed asthma and the secondary outcome variable was presence of wheezing in the previous 12 months among those without physician-diagnosed asthma. Exploratory factor analysis was used to generate factor scores to group VOCs, which were included as indicator variables in the analyses. Associations between exposure to VOCs, physician diagnosed asthma, and wheezing in the previous 12 months were evaluated using multiple logistic regression analyses. Odds ratios are for 1-U increase in level of exposure. RESULTS: Seven of the ten VOC variables loaded on two factors, "aromatic compounds" and "chlorinated hydrocarbons." The geometric mean concentration of VOCs varied from as low as 0.03 microg/m3 for trichloroethene to as high as 14.33 microg/m3 for toluene. Mexican-Americans had the highest personal exposures to benzene (geometric mean=2.38 microg/m3) as compared to non Hispanic whites (geometric mean=1.15 microg/m3) and non-Hispanic Blacks (geometric mean=1.07 microg/m3). The odds of physician-diagnosed asthma were significantly higher among those exposed to aromatic compounds (Adjusted OR=1.63, 95% CI: 1.17-2.27). Among those subjects never diagnosed by a physician to have asthma, a significantly increased odds of one to two wheezing attacks were observed for aromatic compounds (Adjusted OR=1.68, 95% CI: 1.08-2.61) and chlorinated hydrocarbons (Adjusted OR=1.50, 95% CI: 1.01-2.23) as compared to no wheezing. No association with three wheezing attacks or more was observed in the study. CONCLUSION: In this cross-sectional study of a representative sample of the US population, environmental exposures to VOCs, especially aromatic compounds, were associated with adverse respiratory effects. PMID- 17357797 TI - Air pollution, socioeconomic position, and emergency hospital visits for asthma in Seoul, Korea. AB - OBJECTIVE: Some epidemiological literature has observed that air pollution effects on health differed across regional or individual socioeconomic position. This study evaluated whether regional and individual socioeconomic position, as indicated by health insurance premiums, modified the effect of air pollution on hospital visits for asthma. METHODS: Effects of ambient air pollutants (particulate matter, carbon monoxide, sulfur dioxide, nitrogen dioxide, and ozone) on 92,535 emergency out-patient hospital visits for asthma in Seoul, Korea during 2002 were estimated using case-crossover analysis, adjusting for time trend, weather conditions, and seasonality. Next, interactions between air pollutants and Korean National Health Insurance premium (1) for the individual patient and (2) averaged across the patient's residence district, were entered, first singly then jointly, in the models. RESULTS: Relative risks of emergency outpatient hospital visits were all positively and significantly associated with interquartile increases for selected lags for all air pollutants. In the regression model with interaction terms for both individual premium and regional average premium, associations with all five-air pollutants ranged from 1.03 to 1.09 times higher among the lowest premium districts compared to the highest premium districts. Of all the pollutants, nitrogen dioxide showed the strongest associations in lower premium districts compared to the higher premium districts. Individual socioeconomic position did not modify the associations in either the single or joint interaction models. CONCLUSION: In Seoul, community but not individual socioeconomic conditions modified risk of asthma hospital visits on high air pollution days. PMID- 17357798 TI - Age standardized cancer mortality ratios in areas heavily exposed to methyl mercury. AB - OBJECTIVE: Methyl-mercury (MeHg) was discharged from a chemical factory in Minamata, and consequently spread throughout the Shiranui Sea in Kumamoto, Japan. Although many studies have focused on MeHg-induced neurological disorders, the association between MeHg and malignant neoplasms has not been adequately investigated. Therefore, we explored this association using the age standardized mortality ratio (ASMR) in an ecologic study over a wide area allowing for a long empirical induction period. METHODS: The subjects were residents in areas around the Shiranui Sea. We divided these areas into exposure groups 1 (Minamata and Ashikita regions) and 2 (Amakusa region). Exposure group 1 was contaminated from the late 1930s, and exposure group 2 was contaminated from the late 1950s. In addition, exposure group 1 was contaminated more heavily than exposure group 2. There were 92,525 and 152,541 residents in each group in 1960, respectively. We analyzed the cancer ASMR in both exposure groups using data from two reference populations (Japan and Kumamoto prefecture) from 1961 to 1997. There were 94,301,494 and 1,856,192 people in each reference group in 1960, respectively. We abstracted population and mortality data from the censuses and the vital statistics of the prefecture and Japan. RESULTS: An increased leukemia ASMR and a decreased gastric cancer ASMR were observed in both exposure groups, while other ASMRs were around unity and less precise. Furthermore, the leukemia ASMRs were elevated differently between the two exposure groups: the leukemia ASMR was already elevated early in the study period in exposure group 1 and increased gradually in exposure group 2. CONCLUSIONS: While the negative association between MeHg and gastric cancer might be explained by salt intake, the positive association between MeHg and leukemia could not be explained by potential confounders. Despite some limitations mainly due to its ecologic design, this study indicates the necessity of an individual-level study evaluating the association between MeHg and leukemia in regions with exposure to MeHg. PMID- 17357800 TI - Novel fibroblastic onion bulbs in a demyelinating avian peripheral neuropathy produced by riboflavin deficiency. AB - The finding of novel fibroblastic onion bulb-like structures in peripheral nerves is reported for the first time in avian riboflavin deficiency. Day old broiler meat chickens were fed a riboflavin deficient diet (1.8 mg/kg) and were killed on postnatal days 6, 11, 16, 21 and 31, whereas control chickens were fed a conventional diet containing 5.0 mg/kg riboflavin. The fibroblastic onion bulb like structures were found in sciatic and brachial nerves from day 11 onwards and consisted of long cytoplasmic processes of hypertrophied fibroblasts surrounding demyelinated, remyelinated and normally myelinated axons. The fibroblast cytoplasmic processes often enveloped more than one nerve fibre to produce a unique compound-like onion bulb structure. These onion bulb-like structures occurred early in the course of segmental demyelination at the same time as tomacula formation and became increasingly more prominent in the later stages of demyelination and remyelination. The molecular basis of formation of these unique structures requires further study as to the basis of the attraction of the fibroblast processes to nerve fibres associated with myelinating Schwann cells. The model may also be useful in investigating the role of endoneurial fibroblasts in endoneurial fibrosis as the early fibroblastic response in the onion bulbs is distinct from the more usual fibroblastic deposition of collagen in end-stage peripheral nerve disease. PMID- 17357801 TI - Massive myelinolytic leukoencephalopathy in a patient medicated with low-dose oral methotrexate for rheumatoid arthritis: an autopsy report. AB - The authors describe a 68-year-old female who developed a rapidly progressing leukoencephalopathy involving the cerebrum and brain stem. The disease appeared during low-dose oral methotrexate (MTX) therapy for rheumatoid arthritis. An extensive clinical investigation discounted other possible causes of white matter lesions. Autopsy identified an uninterrupted severe demyelinating, partially liquefactive necrosis-like lesion in the white matter accompanied by astrogliosis and occasional swollen axons therein. The lesion was generally symmetrical, and distributed throughout the whole cerebral white matter except for the bilateral temporal lobes and the rostral part of the frontal lobes. The internal capsules and cerebral peduncles were spongy, and the central and lateral parts of the pons, especially the transverse cerebellopontine tracts, were affected similarly. It was of note that the lesion was accompanied by neither vascular diseases nor lymphocyte infiltration. Thus, the pathological findings were similar to those of a severe form of central and extrapontine myelinolysis, and clearly different from ordinary MTX leukoencephalopathy reported in patients receiving intrathecal or intravenous MTX therapy, known as "disseminated necrotizing leukoencephalopathy". Another possibility is that synergistic effects of several white-matter-damaging disorders may have contributed to the hitherto unknown lesion. To our knowledge, this is the first autopsy record that describes an oral MTX-associated neurological disorder. PMID- 17357799 TI - 1-hydroxypyrene as a biomarker of PAH exposure among subjects living in two separate regions from a steel mill. AB - OBJECTIVE: Steel mills are known to be a source of ambient polycyclic aromatic hydrocarbons (PAHs), and increased cancer risk has been reported among neighborhoods previously. In this study, we tried to assess the exposure to PAHs among residents nearby to a large steel mill in Korea by measuring urinary 1 hydroxypyrene (1-OHP). METHODS: Two separate areas at different distances from a steel mill but on the same wind direction were chosen to evaluate the environmental exposures to polycyclic aromatic hydrocarbons. Three-hundred and fifty children living in the vicinity of steel plant ("nearby" group) and 606 children residing much farther from the factory ("remote" group) participated. Urine was collected on three consecutive days, and questionnaires about exposure to passive smoking and food consumption as well as demographics were obtained. Routine monitoring data of ambient pollutants were obtained and particulate matter less than 10 microm (PM10) was analyzed with multiple regressions to assess the associations with urinary 1-OHP. RESULTS: The geometric mean concentration of urinary 1-OHP among nearby group (0.048+/-1.878 micromol/mol creatinine, GM+/-GSD) was approximately 1.3 times higher than that among remote group (0.036+/-2.425 micromol/mol creatinine, GM+/-GSD), and using multiple regression techniques, the difference was significant (P<0.0001) after adjusting for confounding variables. When different periods before the sampling of urine were examined, PM10 averages over 2 days, 3 days, and 1 week prior to urine sampling showed significant associations with urinary 1-OHP levels. CONCLUSION: Our findings are consistent with the interpretation that residents nearby to a steel mill are exposed to PAHs through ambient exposures. PMID- 17357802 TI - Phosphorylation and cleavage of tau in non-AD tauopathies. AB - The tau protein, well known as the primary component of neurofibrillary tangles, also comprises the Pick bodies found in Pick's disease (PiD) and the glial lesions associated with progressive supranuclear palsy (PSP) and cortico-basal ganglionic degeneration (CBD). Many of the tau alterations that are characteristic of Alzheimer's disease have also been identified in PSP and CBD. In this report, we examine three non-AD tauopathies (PSP, CBD, and PiD) for the presence of two specific tau alterations, phosphorylation at Ser422 and truncation at Asp421. We find that truncation at Asp421 is an alteration that is unique to neuronal lesions, occurring in Pick bodies as well as in neurofibrillary tangles, but not in lesions associated with glia. Conversely, phosphorylation at Ser422 is not only present in all these lesions, but identifies additional glial and neuronal pathology in disease-susceptible cortical regions. These results suggest that the molecular alterations of tau that occur during the initial process of tangle formation in AD are similar in non-AD tauopathies, but the middle and later changes are not common to all diseases. PMID- 17357803 TI - Production of D-arabitol by a newly isolated Zygosaccharomyces rouxii. AB - A newly isolated Zygosaccharomyces rouxii NRRL 27,624 produced D-arabitol as the main metabolic product from glucose. In addition, it also produced ethanol and glycerol. The optimal conditions were temperature 30 degrees C, pH 5.0, 350 rpm, and 5% inoculum. The yeast produced 83.4 +/- 1.1 g D-arabitol from 175 +/- 1.1 g glucose per liter at pH 5.0, 30 degrees C, and 350 rpm in 240 h with a yield of 0.48 g/g glucose. It also produced D-arabitol from fructose, galactose, and mannose. The yeast produced D-arabitol and xylitol from xylose and also from a mixture of xylose and xylulose. Resting yeast cells produced 63.6 +/- 1.9 g D arabitol from 175 +/- 1.8 g glucose per liter in 210 h at pH 5.0, 30 degrees C and 350 rpm with a yield of 0.36 g/g glucose. The yeast has potential to be used for production of xylitol from glucose via D-arabitol route. PMID- 17357804 TI - Persistent clinical response of infliximab treatment, over a 4-year period in ankylosing spondylitis. AB - Our aim was to investigate the efficacy, toxicity, and drug discontinuation in patients with ankylosing spondylitis (AS) treated with infliximab. Thirty-five patients with AS, who were enrolled between June 2001 and December 2002 were treated with infliximab. All patients fulfilled the New York revised criteria for AS and had axial disease. Infliximab (5 mg/kg weight), was given intravenously at weeks 0, 2, 6, and every 8 weeks thereafter. If this failed to give an acceptable treatment response, the interval was shortened to 6 or 4 weeks. The patients were followed-up at predefined times according to a standardized protocol. Data concerning infliximab efficacy, tolerability, adverse events, interval, and drug discontinuation were all recorded. Clinical improvement according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% and the Ankylosing Spondylitis Assessment Study group (ASAS) 40%, and ASAS 5/6 response criteria were recorded. Infliximab treatment resulted in a rapid improvement in the BASDAI and ASAS scores in the first year of the treatment, which sustained throughout the fourth year. More specifically, after the third year of treatment 17/35 (48.6%) of patients achieved BASDAI 50% response criteria, 19/35 (54.3%) attained the ASAS 40% and 15/35 (42.9%) reached the ASAS 5/6. After the fourth year of treatment BASDAI 50% was reached by 17/35 (48.6%) of patients, ASAS 40% by 17/35 (48.6%), while ASAS 5/6 was attained by 15/35 (42.9%). The clinical improvement was associated with the reduction of acute phase reactants as measured by C reactive protein levels. After the first year of treatment, the "survival rate" of infliximab was 94.3%, after the second year was 91.4%, after the third year was 85.7% and even after 4 years of treatment still maintained high 77.9%. Six (17.1%) patients were withdrawn during the observational period. Three because of lack of efficacy, two because of allergic reactions and one lost from follow-up. Infliximab was effective, safe, and well tolerated in patients with AS. The clinical response was maintained for a period of 4 years and over, with infliximab survival of 77.9%. PMID- 17357805 TI - Value of fetal cerebral MRI in sonographically proven cardiac rhabdomyoma. AB - BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant phakomatosis associated with intracardiac rhabdomyomas. OBJECTIVE: The aim of our study was to examine the value of cerebral MRI in diagnosing TSC in fetuses with intracardiac rhabdomyomas, applying the TSC Consensus Conference (TSCCC) criteria. MATERIALS AND METHODS: In a prospective manner six consecutive fetuses with cardiac rhabdomyomas (21-34 weeks' gestation) underwent cerebral MRI. The MRI results were correlated with clinical follow-up at 10-34 months after birth, histology, and genetic data. RESULTS: In five of the six fetuses the diagnosis of TSC was established. In two of five fetuses MRI demonstrated cerebral manifestations of TSC that correlated well with severe epilepsy manifesting during the follow-up period. In another two of five fetuses MRI as well as clinical follow-up were normal. One of five pregnancies was terminated and histology demonstrated microscopically small subependymal nodules not demonstrated by MRI. CONCLUSION: The results of our study agree with the available literature that fetal MRI is sufficient for the detection of cerebral lesions in TSC and should be better promoted. The TSCCC criteria can also be applied to fetal MRI. PMID- 17357806 TI - Sonographic findings of ovarian torsion in children. AB - BACKGROUND: The clinical diagnosis of ovarian torsion is challenging and findings on pelvic sonography can be pivotal in making the correct diagnosis. OBJECTIVE: To determine the sonographic characteristics in children of surgically and pathologically proven ovarian torsion. MATERIAL AND METHODS: We performed a retrospective review of the sonograms and medical records of 41 patients with surgically and pathologically proven ovarian torsion at a pediatric hospital between 1994 and 2005. All sonograms were reviewed retrospectively by two pediatric radiologists with attention to the size, echotexture, location, presence of peripheral round cysts, and evidence of flow on Doppler sonography within the torsed ovary. The amount of free pelvic fluid was also recorded. RESULTS: The most common sonographic finding of ovarian torsion was an enlarged ovary/adnexal mass. All torsed adnexa were larger than the normal contralateral ovary, with the median volume 12 times that of the normal contralateral side. The majority (61%, n = 25) of the torsions occurred on the right. Color flow, either venous or arterial, was present in 62% (n = 21/34) of the torsed ovaries for which flow on Doppler sonography was documented. In 63% of the torsed ovaries (n = 26), the torsed adnexa appeared heterogeneous. Ovarian or para-ovarian pathology that may have acted as a potential lead point was present in 55% (n = 24) of torsed ovaries. The volume ratio of the torsed to normal ovary can predict the presence of an ovarian mass within the torsed ovary. In 70% of torsed ovaries with a volume ratio greater than 20, an ovarian mass was present, and in approximately 90% of those with a volume ratio less than 20, an internal mass was absent. CONCLUSION: An enlarged heterogeneous appearing ovary is the most common finding in ovarian torsion. The presence or absence of flow by Doppler sonography is not helpful in the diagnosis. The volume ratio of the torsed to the normal ovary can predict the presence of an internal mass within the torsed adnexa. PMID- 17357807 TI - Branch retinal artery occlusion associated with compound heterozygous genotype for methylenetetrahydrofolate reductase. AB - We present a case in which mfERG and OCT helped to make a diagnosis of an old BRAO in the setting of compound heterozygous MTHFR genotype. A 44-year-old woman presented for evaluation of a 10 month history of persistently cloudy vision OS. She had been worked up previously for MS versus BRAO, and she was on coumadin, folate, and multivitamin at the time of presentation. The patient has a fraternal twin sister who was diagnosed with MS. Dilated fundus examination OS showed subtle inferior optic atrophy with slight narrowing of the inferotemporal retinal artery, and HVF test revealed a superonasal depression OS. mfERG also showed superonasal depression OS. Retinal origin of the chief complaint was further confirmed by OCT, which showed thinning of the NFL in the corresponding region of the retina OS. Coagulopathy evaluation revealed C677T/A1298C compound heterozygous genotype for MTHFR, and plasma homocysteine level after 6 months of folate and multivitamin supplementation was 10 microM (reference range 4-10 microM). The patient was diagnosed with BRAO and maintained on coumadin therapy. PMID- 17357808 TI - Contemporary adrenal scintigraphy. AB - INTRODUCTION: High-resolution computed tomography (CT) and magnetic resonance (MR) imaging have replaced scintigraphy as primary imaging modalities for the evaluation of adrenal diseases. DISCUSSION: Thin-slice CT, CT contrast washout studies and MR pulse sequences specifically designed to identify adrenal lipid content have radically changed the approach to anatomic imaging and provide unique insight into the physical characteristics of the adrenals. With a confirmed biochemical diagnosis, further evaluation is often unnecessary, especially in diagnostic localization of diseases of the adrenal cortex. However, despite the exquisite detail afforded by anatomy-based imaging, there are not infrequently clinical situations in which the functional insight provided by scintigraphy is crucial to identify adrenal dysfunction and to assist in localization of adrenocortical and adrenomedullary disease. The introduction of hybrid PET/CT and SPECT/CT, modalities that directly integrate anatomic and functional information, redefine the radiotracer principle in the larger context of high-resolution anatomic imaging. Instead of becoming obsolete, scintigraphy is an element of a device that combines it with CT or MR to allow a direct correlation between function and anatomy, whereby the combination creates a more powerful diagnostic tool than the separate component modalities. PMID- 17357809 TI - False positive 18F-FDG PET/CT due to gynaecomastia. PMID- 17357811 TI - Community pharmacists' views, attitudes and early experiences of over-the-counter simvastatin. AB - AIM: To describe community pharmacists' views, attitudes and early experiences of OTC simvastatin. METHOD: A cross-sectional postal questionnaire survey of the main pharmacist in 2000 randomly selected community pharmacy premises in Great Britain (approximately 15%). MAIN OUTCOME MEASURE: The questionnaire comprised items on: attitudes to OTC simvastatin; continuing education; sales; and general views and experiences. Data were analysed using descriptive statistics and content analysis of responses to open questions. RESULTS: Questionnaires were returned by 1,156 community pharmacists (57.8%). Nine hundred and fifty-six respondents (82.7%) reported no sales of simvastatin in the previous fourteen days. Eighty-two (7.1%) sold one pack, 40 (3.5%) sold two packs and 18 (1.6%) sold three packs or more (60 did not answer). Almost all respondents (1,086, 93.9%) stated that they had participated in continuing education. Most (691/1,148, 60.1%) strongly agreed or agreed that they were entirely confident about selling simvastatin and that community pharmacists could make an appropriate risk assessment for the use of simvastatin (898/1,149, 78.2%). Responses to the open question identified a number of themes including: need for access to clinical information; cost as a barrier to supply; those purchasing were least likely to benefit; and the lack of an evidence base for the OTC dose. CONCLUSION: Community pharmacists surveyed had undertaken an array of continuing education and felt confident to undertake cardiovascular risk assessment. However, very few sales of OTC simvastatin had been made and a variety of issues were identified, particularly relating to the evidence base, access to clinical information, cost and the product licence. PMID- 17357812 TI - Getting the edge: neural precursor selection. AB - A key issue in development is how to specify single isolated precursor cells to adopt a distinct fate from a group of naive cells. Studies on the development of Drosophila external sensory (ES) organs have revealed multiple mechanisms to specify single sensory organ precursors (SOPs) from clusters of cells with equivalent neural potential. Initially single SOPs are selected in part through cell-cell competition from clusters of ectodermal cells that express proneural proteins. To reinforce the singularity, lateral inhibition through the Delta/Notch system and feedback regulations lead to exclusive expression of proneural proteins in SOPs. As transcriptional activators, proneural proteins execute a genetic program in SOP cells for the development of an eventually ES organ. In this article, we will summarize recent advances on how transcriptional regulation, protein degradation, endocytosis and gene silencing by microRNA participate in SOP specification. PMID- 17357813 TI - Effects of Helicobacter hepaticus on the proteome of HEp-2 cells. AB - Helicobacter hepaticus infects the bowel and biliary tree of several animals, producing inflammation. Colonisation of mouse livers can induce hepatocellular carcinomas. The effects of H. hepaticus on the proliferation and global protein expression of human HEp-2 cells were studied by examining the changes in the protein profiles of cells exposed to the bacterium. HEp-2 cells were grown for four days under a microaerobic atmosphere or under the same conditions in co cultures with H. hepaticus at various inoculum densities. Enlargement, distension and elongation of HEp-2 cells were observed in co-cultures with H. hepaticus. The number of live cells declined by only an order of magnitude at bacterial inocula of approximately 10(9)cfu/ml, but were reduced to less than 10(3)cells/ml at approximately 10(10)cfu/ml bacteria inocula. Protein expression by HEp-2 cells was investigated employing two-dimensional gel electrophoresis. In cells grown with or without bacteria, 17 differentially expressed proteins were identified by tandem mass spectrometry. These proteins participated in several biological functions including amino acid metabolism, cell growth and proliferation, stress response, protein translation and modification, etc. The onset of a catastrophic killing of HEp-2 cells at a bacterial density of approximately 10(9)cfu/ml suggested a multimodal action for H. hepaticus infection, and the modulation of the expression of proteins involved in different biological functions showed that the presence of H. hepaticus has broad effects on the physiology of HEp-2 cells. PMID- 17357814 TI - Prevalence of Campylobacter spp. in poultry and poultry products for sale on the Bulgarian retail market. AB - The aim of this study was to investigate the presence of Campylobacter spp. in poultry and poultry products available for the consumers at retail markets in Bulgaria. Samples (n = 210) of poultry carcasses and poultry products for sale at the retail market in Bulgaria were analysed for the presence of Campylobacter spp., of these 35 frozen whole carcasses, 135 chilled poultry cuts (45 wing cuts, 45 thigh cuts and 45 fillet) and 40 thermally treated (ready-to-eat) poultry products. The results obtained showed that 35.2% of the frozen poultry carcasses for sale in the markets were Campylobacter contaminated. In the chilled poultry cuts Campylobacter was isolated at the highest percentage in wing- and thigh cuts, 91.1% and 88.9%, respectively. The fillet samples were contaminated by Campylobacter in 48.9% of cases. In the chilled poultry products as well as in the frozen carcasses C. jejuni (74.8%/70.3%) was the most commonly isolated Campylobacter species, with the remainder being C. coli (25.2%/29.7%). Campylobacter spp. were not detected in the thermally treated poultry products. PMID- 17357816 TI - Effects of subsample size on seasonal and spatial comparisons of stream macroinvertebrate communities. AB - We examined the effect of subsample size on the accuracy of information obtained from aquatic macroinvertebrate assemblage samples. Subsamples containing 100 organisms or 300 organisms were compared on the bases of processing time and the ability to discern ecological differences among samples. Independently of subsample size, assemblages differed between study streams, primarily reflecting an intermittent vs. permanent stream difference, and between seasons at most streams. It required, on average, two additional hours to process the larger subsamples. Larger subsamples gave significantly higher estimates of total richness and Ephemeroptera, Plecoptera, and Trichoptera (EPT) richness, but the relative abundances of many assemblage subsets (e.g., EPT organisms and most functional feeding groups) were similar using both subsample sizes. Larger subsamples did not typically enhance the ability to discriminate between samples from different seasons, but did more accurately distinguish among streams when differences were subtle. They also appeared to avoid Type I error in comparisons of compositionally similar reaches within a study stream. PMID- 17357817 TI - Effect of spatial variability of storm on the optimal placement of best management practices (BMPs). AB - It is significant to design best management practices (BMPs) and determine the proper BMPs placement for the purpose that can not only satisfy the water quantity and water quality standard, but also lower the total cost of BMPs. The spatial rainfall variability can have much effect on its relative runoff and non point source pollution (NPSP). Meantime, the optimal design and placement of BMPs would be different as well. The objective of this study was to discuss the relationship between the spatial variability of rainfall and the optimal BMPs placements. Three synthetic rainfall storms with varied spatial distributions, including uniform rainfall, downstream rainfall and upstream rainfall, were designed. WinVAST model was applied to predict runoff and NPSP. Additionally, detention pond and swale were selected for being structural BMPs. Scatter search was applied to find the optimal BMPs placement. The results show that mostly the total cost of BMPs is higher in downstream rainfall than in upstream rainfall or uniform rainfall. Moreover, the cost of detention pond is much higher than swale. Thus, even though detention pond has larger efficiency for lowering peak flow and pollutant exports, it is not always the determined set in each subbasin. PMID- 17357815 TI - Involvement of Hif-1 in desferrioxamine-induced invasion of glioblastoma cells. AB - Glioblastoma multiforme are highly invasive brain tumors. Experimental approaches focus on unravelling the mechanisms of invasion, this being a major reason for the poor prognosis of these tumors. Our previous results hinted towards involvement of the iron metabolism in invasion. In this study, we examined the effect of iron depletion on the invasive phenotype of glioblastoma cells. Transwell Matrigel invasion assays were used to monitor iron-dependent invasion of human glioblastoma cell lines U373MG and DBTRG05MG. Intracellular iron concentrations were modulated by applying desferrioxamine (DFO) and ferric ammonium citrate (FAC). We detected enhanced invasion of glioblastoma cells upon DFO-induced iron depletion. Treatment of cells with FAC strongly inhibited invasion. DFO treatment resulted in hypoxia-inducible factor 1 (Hif-1)-mediated induction of urokinase plasminogen activator receptor and matrix metalloproteinase 2. Further, RNA interference-mediated repression of urokinase plasminogen activator receptor inhibited DFO-induced invasion. Our data demonstrate a direct effect of DFO on Hif-1 expression resulting in activation of factors associated with ECM degradation and invasion of glioma cells. These findings caution on utilization of DFO and other iron chelators in the treatment of tumors with invasive potential. PMID- 17357818 TI - The statistical investigation on airborne fungi and pollen grains of atmosphere in Izmir-Turkey. AB - This study aims to investigate the differences in the concentrations of airborne fungi and pollens between the towns located in the province of Izmir and to determine the factors contributing to these differences. Five stations in each of four towns (Buca, Konak, Bornova, and Karsiyaka) were randomly selected as the research areas. Fungus (cfu/m(3)) and pollen counts (cm(2)/pollen count) in the air samples collected from each station between June 2003 and May 2004 were measured. The results revealed that whereas Karsiyaka had the highest fungus concentration (521.33 +/- 777.1), Buca and Bornova had the lowest concentration (482.67 +/- 308.44). The mean fungus concentration in the province of Izmir was 501.5 +/- 486.7. Pollen concentration was the highest in Konak (486.67 +/- 839.06) and the lowest in Bornova (369.83 +/- 551.13). Fungus and pollen concentrations revealed no difference between the towns (p > 0.05). The relationship between pollen-fungus concentrations and temperature-dust-humidity sulphur-dioxide was investigated but it was found statistically insignificant (p > 0.05). As a result of regression analysis, it was determined that correlation of atmospheric parameters had no effects on pollen and fungus concentrations (p > 0.05). PMID- 17357819 TI - Water quality trend analysis for the Karoon River in Iran. AB - The Karoon River basin, with a basin area of 67,000 km(2), is located in the southern part of Iran. Monthly measurements of the discharge and the water quality variables have been monitored at the Gatvand and Khorramshahr stations of the Karoon River on a monthly basis for the period 1967-2005 and 1969-2005 for Gatvand and Khorramshahr stations, respectively. In this paper the time series of monthly values of water quality parameters and the discharge were analyzed using statistical methods and the existence of trends and the evaluation of the best fitted models were performed. The Kolmogorov-Smirnov test was used to select the theoretical distribution which best fitted the data. Simple regression was used to examine the concentration-time relationships. The concentration-time relationships showed better correlation in Khorramshahr station than that of Gatvand station. The exponential model expresses better concentration - time relationships in Khorramshahr station, but in Gatvand station the logarithmic model is more fitted. The correlation coefficients are positive for all of the variables in Khorramshahr station also in Gatvand station all of the variables are positive except magnesium (Mg2+), bicarbonates (HCO3-) and temporary hardness which shows a decreasing relationship. The logarithmic and the exponential models describe better the concentration-time relationships for two stations. PMID- 17357820 TI - Quantitative assessment of desertification in south of Iran using MEDALUS method. AB - The main aim of this study was the quantitative assessment of desertification process in the case study area of the Fidoye-Garmosht plain (Southern Iran). Based on the MEDALUS approach and the characteristics of study area a regional model developed using GIS. Six main factors or indicators of desertification including: soil, climate, erosion, plant cover, groundwater and management were considered for evaluation. Then several sub-indicators affecting the quality of each main indicator were identified. Based on the MEDALUS approach, each sub indicator was quantified according to its quality and given a weighting of between 1.0 and 2.0. ArcGIS 9 was used to analyze and prepare the layers of quality maps using the geometric mean to integrate the individual sub-indicator maps. In turn the geometric mean of all six quality maps was used to generate a single desertification status map. Results showed that 12% of the area is classified as very severe, 81% as severe and 7% as moderately affected by desertification. In addition the plant cover and groundwater indicators were the most important factors affecting desertification process in the study area. The model developed may be used to assess desertification process and distinguish the areas sensitive to desertification in the study region and in regions with the similar characteristics. PMID- 17357821 TI - Consumption rate of phytonematodes by Pergalumna sp. (Acari: Oribatida: Galumnidae) under laboratory conditions determined by a new method. AB - Although several generalist species of Pergalumna are known to be nematode predators, the potential of oribatid mites as natural enemies of phytonematodes has been underestimated. The objective of this work was to estimate the consumption rate of a Pergalumna sp. when feeding on two major pest nematodes, Meloidogyne javanica and Pratylenchus coffeae, under laboratory conditions. A new method was used, in which live nematodes are offered to mites and subsequently consumption is quantified based on the sclerotized, well preserved structures in the mite's fecal pellets. The assay was evaluated during 5 days, at 25 degrees C and 96% relative humidity, with three replicates for each nematode species. Every replicate consisted of a group of four mites isolated in an arena, to which 400 nematodes were transferred daily. The daily produced fecal pellets were mounted in Hoyer's medium for examination under a microscope. The nematode buccal stylets and cephalic frameworks were counted to estimate the number of nematodes consumed. It was estimated that a single mite daily ingested 18.3 +/- 0.8 (mean +/- SE) M. javanica (J(2) juveniles) or 41.6 +/- 7.2 P. coffeae (juveniles + adults), the maximal daily consumption being 34 M. javanica and 73 P. coffeae. The method showed to be practical, precise and suitable for laboratory studies in which nematophagous mites classified as engulfers are included. PMID- 17357822 TI - Scaling up tests on virulence of the cassava green mite fungal pathogen Neozygites tanajoae (Entomophthorales: Neozygitaceae) under controlled conditions: first observations at the population level. AB - Virulence of entomopathogens is often measured at the individual level using a single host individual or a group of host individuals. To what extent these virulence assessments reflect the impact of an entomopathogen on their host in the field remains largely untested, however. A methodology was developed to induce epizootics of the cassava green mite fungal pathogen Neozygites tanajoae under controlled conditions to evaluate population-level virulence of two (one Beninese and one Brazilian) isolates of the entomopathogen--which had shown similar individual-level virulence but different field impacts. In unrepeated separate experiments we inoculated mite-infested potted cassava plants with either 50 or 25 live mites (high and low inoculum) previously exposed to spores of N. tanajoae and monitored the development of fungal infections for each isolate under the same conditions. Both isolates caused mite infections and an associated decline in host mite populations relative to the control (without fungus) in all experiments, but prevalence of the fungus varied with isolate and increased with inoculum density. Peak infection levels were 90% for the Beninese isolate and 36% for the Brazilian isolate at high inoculum density, and respectively 17% and 25% at low inoculum density. We also measured dispersal from inoculated plants and found that spore dispersal increased with host infection levels, independent of host densities, whereas mite dispersal varied between isolates. These results demonstrate that epizootiology of N. tanajoae can be studied under controlled conditions and suggest that virulence tests at the population level may help to better predict performance of fungal isolates than individual-level tests. PMID- 17357823 TI - Surgical margins in radical prostatectomy: a comparison between retropubic and laparoscopic surgery. AB - OBJECTIVES: To compare positive surgical margins in both radical retropubic prostatectomies and laparoscopic surgery in two reference centres in Brazil. MATERIALS AND METHODS: One hundred and seventy nine pathological studies from patients, who underwent radical prostatectomy due to prostate adenocarcinoma, 89 submitted to retropubic surgery and 90 to laparoscopic surgery, were analyzed. Inclusion criteria Patients with PSA 65 bpm. In group 1, misalignment was significantly lower than in groups 2 and 3. On a segment-based analysis, overall feasibility was therefore significantly higher in group 1 vs group 2 and vs group 3. Images of good quality were significantly higher in group 1 (95.4%) than in group 2 (87%) and group 3 (71.8%). The higher image quality in group 1 impacts on the overall diagnostic accuracy of the exam. Indeed overall sensitivity is significantly higher in group 1 (89.5%) than in group 2 (86%) and group 3 (82.8%) and overall specificity is significantly higher in group 1 than in group 3. CONCLUSIONS: Multidetector computed tomography has a high feasibility and diagnostic accuracy for the evaluation of coronary artery disease in an unselected population. Good patient preparation (optimized beta-blocker therapy, correct breathing instructions) is essential for evaluating native coronary arteries while preparation with a beta-blocker is less relevant in bypass graft patients. PMID- 17357825 TI - Mitochondrial DNA polymorphisms and the risk of Parkinson's disease in Taiwan. AB - A critical role of mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD). The association of mitochondrial DNA (mtDNA) polymorphisms 9055G/A, 10398G/A and 13708G/A with PD has been controversial. In this study we analyzed whether these three genetic polymorphisms are associated with PD in a cohort of 416 PD cases and 372 ethnically matched controls. The allele frequency distribution of any of these three analyzed polymorphisms was not significantly different between the cases and the controls. None of the six haplotypes derived influences risk of PD. Notably, after stratification by age, individuals over 70 years of age carrying the haplotype 9055G-10398A-13708G demonstrated a significant decrease in risk of developing PD (OR = 0.44, 95% CI = 0.24-0.80, p = 0.008). These results suggest that the mtDNA haplotype 9055G-10398A-13708G plays a role in PD susceptibility among Taiwanese people older than 70 years of age. PMID- 17357826 TI - Burnout among women: associations with demographic/socio-economic, work, life style and health factors. AB - This study examined the occurrence of low/high burnout among women and the demographic/socio-economic, work, life-style, and health "correlates" of high burnout. The sample consisted of 6.000 randomly selected women from the general population, of which 3.591 participated. The design was cross-sectional. The univariate analyses showed that about 21% of the women had high burnout, and compared to those with low burnout, they were more often younger, divorced, blue collar workers, lower educated, foreigners, on unemployment/retirement/sick leave, financially strained, used more medication and cigarettes, reported higher work demands and lower control/social support at work, more somatic problems (e.g. pain) and depression. The regression analysis showed that only age, sick leave, financial strain, medication, work demands, depression and somatic ailments were independently associated with high burnout. Thus, women with high burnout were apparently faring poorly financially, emotionally and physically. Considering our findings, interventions to alleviate their problems may be necessary. We may have provided new insights into women's burnout experiences, but longitudinal studies are warranted to firmly identify "determinants" of burnout. PMID- 17357827 TI - Recurrent dural based cystic cerebellar haemangioblastoma in a patient with von Hippel-Lindau disease. AB - Surgical excision of cerebellar haemangioblastomas, once they become Symptomatic, is the standard treatment in patients with von Hippel-Lindau disease. This case report describes a von Hippel-Lindau disease patient with a rare recurrent symptomatic dural based cystic haemangioblastoma. PMID- 17357828 TI - Nuclear/cytoplasmic localization of Akt activity in the cell cycle. AB - The serine/threonine protein kinase Akt (also known as PKB) is a proto-oncogene and one of the most frequently hyperactivated kinases in human cancer. Its activation downstream of growth-factor-stimulated phosphatidylinositide-3'-OH kinase activity plays a role in the control of cell cycle, cell growth, apoptosis and cell energy metabolism. Akt phosphorylates some thousand downstream substrates, including typical cytoplasmic as well as nuclear proteins. Accordingly, it is not surprising that Akt activity can be found in both, the cytoplasm and the nucleus. Here we report the cell cycle regulation of nuclear and cytoplasmic Akt activity in mammalian cells. These data provide new insights into the regulation of Akt activity and have implications for future studies on the regulation of the wide variety of different nuclear and cytoplasmic Akt substrates. PMID- 17357829 TI - Biotechnology applications of amino acids in protein purification and formulations. AB - Amino acids are widely used in biotechnology applications. Since amino acids are natural compounds, they can be safely used in pharmaceutical applications, e.g., as a solvent additive for protein purification and as an excipient for protein formulations. At high concentrations, certain amino acids are found to raise intra-cellular osmotic pressure and adjust to the high salt concentrations of the surrounding medium. They are called "compatible solutes", since they do not affect macromolecular function. Not only are they needed to increase the osmotic pressure, they are known to increase the stability of the proteins. Sucrose, glycerol and certain amino acids were used to enhance the stability of unstable proteins after isolation from natural environments. The mechanism of the action of these protein-stabilizing amino acids is relatively well understood. On the contrary, arginine was accidentally discovered as a useful reagent for assisting in the refolding of recombinant proteins. This effect of arginine was ascribed to its ability to suppress aggregation of the proteins during refolding, thereby increasing refolding efficiency. By the same mechanism, arginine now finds much wider applications than previously anticipated in the research and development of proteins, in particular in pharmaceutical applications. For example, arginine solubilizes proteins from loose inclusion bodies, resulting in efficient production of active proteins. Arginine suppresses protein-protein interactions in solution and also non-specific adsorption to gel permeation chromatography columns. Arginine facilitates elution of bound proteins from various column resins, including Protein-A or dye affinity columns and hydrophobic interaction columns. This review covers various biotechnology applications of amino acids, in particular arginine. PMID- 17357830 TI - The dose-volume interaction in adult supratentorial low-grade glioma: higher radiation dose is beneficial among patients with partial resection. AB - PURPOSE: To evaluate the hypothesis that adults with partially resected (PR<50% resection) supratentorial low-grade glioma (LGG) benefit from higher doses of radiation. METHODS: Patients receiving post-operative radiation for WHO grade I II LGG at the University of Western Ontario between 1979 and 2001 were studied. Patient characteristics evaluated included: age, gender, symptom duration>30 days, seizures at presentation, Karnofsky performance status (KPS)<70, astrocytoma pathology (AS), and radiation dose. A Cox proportional hazard regression model was constructed to test the influence of radiation dose. RESULTS: One hundred and seven patients were analyzed. Patients who had PR were not significantly different from those with STR (subtotal/total resection) in terms of patient characteristics. Median survival (MST) of PR patients who received50 Gy had a MST of 109.2 months. The interaction of radiation dose and extent of resection was tested after controlling for other patient factors by Cox regression model. The interaction was highly significant for both OS and PFS (P=0.013 and P=0.003, respectively). This model remained significant after excluding six patients receiving doses<42 Gy (OS, P=0.024, and PFS, P=0.001). CONCLUSIONS: The outcome for patients with LGG is dependent on extent of tumor resection and radiation dose. Patients with PR should be considered for higher radiation dose schedules (>50 Gy). Future trials on therapeutic strategies for LGG should consider stratification of patients by extent of tumor resection. Our data suggests that one dose does not fit all. PMID- 17357831 TI - Enterocutaneous fistula and small bowel evisceration of twenty-five years' duration: successful surgical and nutritional management. PMID- 17357832 TI - Synthetic serine protease inhibitor, gabexate mesilate, prevents nuclear factor kappaB activation and increases TNF-alpha-mediated apoptosis in human pancreatic cancer cells. AB - Gabexate mesilate (GM), a synthetic serine protease inhibitor, suppresses nuclear factor-kappaB (NF-kappaB) activity in human monocytes or human umbilical vein endothelial cells (HUVECs). In this study we examine whether GM also suppresses NF-kappaB activation and induces apoptosis in human pancreatic cancer cell lines. The addition of tumor necrosis factor alpha (TNF-alpha) did not change the rates of growth of BxPC-3 and MIA PaCa-2. However, in the presence of GM and TNF-alpha, proliferation decreased in a dose-dependent manner. GM- and TNF-alpha-treated cells exhibited morphologic changes indicative of apoptosis, including chromatin condensation and nuclear fragmentation. The NF-kappaB activity of both cell lines was increased by the addition of TNF-alpha, while TNF-alpha-induced NF-kappaB activity was suppressed by prestimulation with GM in a dose-dependent manner. Caspase 3 and 7 activity was significantly increased by TNF-alpha with GM stimulation. Furthermore, GM also suppressed the invasive potential of both cell lines. These results indicate that GM inhibits TNF-alpha-induced NF-kappaB activation and enhances apoptosis in human pancreatic cancer cell lines. PMID- 17357834 TI - Acute abdominal pain in irritable bowel syndrome patients: not always an acute exacerbation. PMID- 17357833 TI - Fructose malabsorption may be gender dependent and fails to show compensation by colonic adaptation. AB - Fructose malabsorption is linked to gastrointestinal and other unusual symptoms. Polymers of fructose are also recognized prebiotics. While some prebiotics can self-adapt when consumed regularly (resulting in decreased breath hydrogen and symptoms), we wondered whether self-adaptation occurs with basic fructose. We evaluated 90 subjects (61 females). Each completed a diet questionnaire and underwent a fructose challenge. Breath hydrogen and quantified symptom scores were recorded. Group comparisons for sum of breath hydrogen and total symptom scores were evaluated with the Mann-Whitney U test. Spearman's correlation coefficient and chi(2) or Fisher's exact test were used as appropriate. Malabsorption occurred in 29 patients (32.2%) and low-grade symptoms without malabsorption in 30 (33%). Women complained of symptoms more frequently (p = 0.04) and exhibited more fructose malabsorption (p = 0.0527). Breath hydrogen correlated with symptoms (r = 0.516, p = 0.0037). Adaptation with increasing pretest fructose intake was absent. We conclude that gender may influence fructose malabsorption and there is no adaptation to regular consumption. PMID- 17357835 TI - Haptoglobin polymorphisms are associated with Crohn's disease, disease behavior, and extraintestinal manifestations in Hungarian patients. AB - Functional differences and association with inflammatory disorders were found relating to three major haptoglobin (Hp) phenotypes. Our aim was to investigate Hp polymorphisms in Hungarian patients with Crohn's disease (CD). Four hundred sixty-eight CD patients and 384 healthy controls were examined. Hp phenotypes were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting of the sera. The frequency of the Hp(1) allele was significantly higher in CD (0.395; OR, 1.24; 95% CI, 1.02-1.52; P=0.03) compared to controls (0.345). In CD, Hp phenotype was associated with disease behavior (OR [Hp(2-1) vs other], 2.06; 95% CI, 1.29-3.28 for inflammatory behavior). Furthermore, an increased frequency of primary sclerosing cholangitis was observed in the Hp 2-2 compared to the Hp 1-1 phenotype (6.5% vs. 0.0%; P=0.039). We conclude that the Hp polymorphism is associated with CD, inflammatory disease behavior, and primary sclerosing cholangitis in Hungarian patients. Further studies are required to evaluate the significance of Hp polymorphisms in other populations from geographically diverse regions. PMID- 17357836 TI - Capsule endoscopy changes patient management in routine clinical practice. AB - Our objective was to evaluate the diagnostic yield and effect of capsule endoscopy on patient management in routine clinical practice. Three hundred examinations were performed (176 females; mean age, 51 years), with a median follow-up of 17 months. Indications included overt bleeding (n=55), anemia (n=104), suspected Crohn's disease (n=68), celiac disease (n=35), suspected functional symptoms (n=23), polyposis (n=5), and miscellaneous (n=10). The overall diagnostic yield was 39%, but it was notably higher in overt bleeders, 66%, compared to 46% in the anemia group (P<0.025), 32% in the suspected Crohn's group (P<0.001), and 17% in the functional group (P<0.001). As a result of capsule endoscopy, management was altered in 26% of patients. This study shows that capsule endoscopy has both a high diagnostic yield and an impact on subsequent patient management. These data further support the role of capsule endoscopy in routine clinical practice. PMID- 17357837 TI - Nasal septal perforation in an adolescent girl with Crohn's disease: a rare extraintestinal manifestation. AB - Crohn's Disease (CD) is a chronic granulomatous inflammatory bowel disease which may also involve the extraintestinal organs such as joints, liver, skin and perianal tissue. Involvement of the aerodigestive tract is quite rare in CD. We report a 16-year-old girl with CD and nasal perforation as an extraintestinal manifestation of the disease. PMID- 17357838 TI - Reasons why patients infected with chronic hepatitis C virus choose to defer treatment: do they alter their decision with time? AB - This study was designed to determine the percentage of treatment-naive patients infected with chronic hepatitis C virus who make an informed choice to forego (defer) treatment with pegylated interferon regimens in the absence of any medical, psychosocial, or other contraindications, and to reassess their decision by using a questionnaire at least 1 year later. Patient charts dating from 2001 were retrieved and retrospectively analyzed for the following data: patient age, gender, race, hepatitis C viral load, genotype, liver biopsy results, hepatic imaging results, peak alanine aminotransferase (ALT) levels, comorbid conditions, source of infection, estimated duration of infection, and reasons given by the patient for declining pegylated interferon-based treatment at the time of their consultation. A questionnaire survey sought to determine their satisfaction with their initial decision. Of 446 patient charts reviewed, 280 patients were treatment-naive and were judged to have no contraindications to receiving interferon-based therapy. Of these, 115 (41%) opted to defer treatment and are the subject of this analysis. Women declining therapy outnumbered men by approximately 3 to 2. Middle-aged patients (45-55 years) were most likely to choose expectant therapy compared with older or younger individuals. The proportion of African American patients who deferred therapy (48%) was higher than non-African American patients (36.6%). More than 90% of the patients choosing to be followed were genotype 1. Peak ALT values were normal in 37% and <2X upper limits of normal (ULN) in another 40%. The estimated duration of chronic hepatitis C infection was >16 years in approximately three-quarters of individuals. The most common source of their infection was intravenous drug use followed by transfusion-related. The most common reason for opting not to receive treatment, given by nearly two-thirds of patients, was the asymptomatic nature of their infection coupled with their concern about side effects of the medications. Approximately 10% had unfavorable social situations, including a lack of support or health insurance, that precluded receiving therapy (despite the availability of indigent care programs offered by the pharmaceutical manufacturers). Only five patients (4.3%) cited doubts about efficacy as the main reason that they did not want to be treated. The questionnaire survey at 1 year found that 79% of the patients confirmed their ongoing satisfaction with their initial decision to decline treatment, and another 10.6% indicated that they were still "moderately satisfied" with their decision and unlikely to change it in the near-future. Only six patients (7%) voiced their current dissatisfaction with expectant management and expressed the desire to have a follow-up discussion about treatment options. Of the remaining three patients (3.5%), two had already started treatment and one was deceased (of non-liver-related causes). A significant proportion of patients infected with hepatitis C virus who are otherwise eligible for therapy opt to defer treatment (41% overall in our series, with African American patients deferring in a higher proportion than non-African American patients). Nearly all of our patients were genotype 1 with clinically and histologically mild hepatitis of reasonably long duration. Our questionnaire survey found that most remained satisfied with their decision to defer treatment at the present time. Few patients cited a perceived low rate of efficacy of pegylated interferon and ribavirin therapy as the principal reason that they chose not to initiate treatment. PMID- 17357839 TI - Macro-aspartate aminotransferase and monoclonal gammopathy: a review of two cases. PMID- 17357840 TI - Capsule endoscopy for obscure GI bleeding: therapeutic yield of follow-up procedures. AB - Positive findings on capsule endoscopy (CE) often prompt a follow-up procedure with therapeutic intent. Our purpose was to review the therapeutic yield of subsequent procedural interventions based on positive CE findings. The medical records of all patients who underwent CE between June 2002 and February 2005 for obscure bleeding were retrospectively reviewed. Fifty-two patients had follow-up procedures based on positive capsule findings. In this group, angiodysplasia was the most common CE finding (n=30), with therapeutic intervention performed in 16 cases (53%). Fresh blood without clear lesion was the second most common finding (n=9), with therapeutic intervention performed in 6 cases (67%). Overall, a therapeutic intervention was performed in 33 of the 52 follow-up procedures (63%). Positive capsule findings directed further procedural investigation in 52 cases, with a high therapeutic yield of 63% in those cases. The long-term efficacy of such interventions warrants further investigation. PMID- 17357841 TI - Lactobacillus rhamnosus GG exacerbates intestinal ulceration in a model of indomethacin-induced enteropathy. AB - Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) were assessed for their potential to prevent indomethacin-induced ulceration in the small intestine of Sprague-Dawley rats. Rats were gavaged skim milk, LGG, or Bb12 twice daily for 14 days. Between days 7-14, rats were gavaged indomethacin (Indo; 6 mg/kg). At sacrifice, small intestine was scored for ulceration and sampled for histologic, immunohistochemical, and myeloperoxidase (MPO) analyses. Indo+LGG treated rats exhibited a 2.3-fold increase in MPO activity and a 9.8-fold increase in ulceration area compared to Indo-treated controls; these parameters did not differ significantly between Indo+Bb12 and Indo-treated controls. Crypt cell apoptosis decreased by 82% in Indo+Bb12-treated and 55% in Indo+LGG-treated rats compared to Indo-treated controls. Proliferation increased by 209% in Indo+LGG-treated animals compared to Indo-treated controls. Bb12 did not reduce indomethacin-induced intestinal ulceration, whereas LGG actually increased some indicators of injury. LGG and Bb12, at the doses tested, cannot alleviate indomethacin-induced intestinal injury. PMID- 17357842 TI - Development of pancreatic acinar cell metaplasia after successful administration of omeprazole for 6 months in rats. AB - Long-term use of proton pump inhibitors (PPIs) has been reported to worsen corpus atrophic gastritis in patients with Helicobacter pylori infection. On the other hand, PPIs have been associated with fundic gland-type gastric polyps and various histological changes. In the present study, we attempted to establish a protocol for omeprazole (OPZ) administration to rats over a longer period and examined the morphological changes in the gastric mucosa after administration of OPZ for 6 months. A total of 34 Wistar rats (8 weeks old) were used. In a preliminary experiment to determine the appropriate dose of OPZ, the rats had ad libitum access to food containing different doses of OPZ for 1 month. We found an approximate dose of 100 mg/kg body weight/day of OPZ to be most suitable from the point of view of intragastric pH, body weight, and serum gastrin level. In the experiment proper, rats were divided into two groups, either control or OPZ diets, and morphological changes in the gastric mucosa in each group were then examined by hematoxylin and eosin and immunohistochemical staining with alpha amylase, trypsin, and chromogranin A. Multiple vacuolar degeneration of parietal cells and numerous small mucous cells were evident at 1 month after treatment with OPZ. At 6 months after treatment with OPZ, cystic degeneration and acinar cell-like cells containing red granules positive for alpha-amylase and trypsin and negative for chromogranin A were detected in the OPZ rats. The serum gastrin level in the OPZ group was significantly higher than that in the control group. We have established a protocol for long-term administration of OPZ in rats that is a useful model for analyzing morphological changes after long-term PPI therapy. Long-term OPZ treatment causes hypergastrinemia and pancreatic acinar cell metaplasia in this animal model. PMID- 17357843 TI - Acute pulmonary embolism as the first manifestation of hepatocellular carcinoma complicated with tumor thrombi in the inferior vena cava: surgery or not? PMID- 17357844 TI - Advertising campaigns of sterol-enriched food. An often neglected cause of reduced compliance to lipid lowering drug therapy. PMID- 17357845 TI - Hyperglobulinemia in amiodarone-induced pneumonitis. AB - BACKGROUND: Amiodarone is a very effective antiarrhytmic drug. However its use may be accompanied by side effects. Hyperglobulinemia was not described in association with amiodarone treatment. MATERIALS AND METHODS: Fifteen patients, who developed hyperglobulinemia while on amiodarone therapy, were identified among the patients hospitalized in our hospital. Serum globulin concentration was measured prior to, during and after amiodarone therapy. RESULTS: In 11 of the 15 patients with amiodarone-associated hyperglobulinemia, amiodarone treatment had to be stopped because of amiodarone-induced complications, nine of them had pneumonitis. Mean serum globulin level rose during amiodarone therapy from 2.48 +/- 0.51 g/dL to 4.11 +/- 0.71 g/dL (p = 0.001), and declined after it was stopped to 2.80 +/- 0.49 g/dL (p = 0.001). In 50 patients treated by amiodarone, serum globulin was similar to that found in 50 patients with ischemic heart disease not treated by amiodarone [2.64 +/- 0.39 g/dL and 2.56 +/- 0.29 g/dL respectively (p = 0.21)]. CONCLUSIONS: In some patients amiodarone therapy may be associated with hyperglobulinemia. The incidence of this association is not known. Most of the patients with amiodarone-associated hyperglobulinemia have amiodarone-induced toxicity, mainly pneumonitis. Amiodarone therapy does not cause a general increase in serum globulins. Hyperglobulinemia may be a marker for a damaged organ, or it may have a pathogenetic role in the induction of pneumonitis. PMID- 17357846 TI - Mycobacterium tuberculosis Antigen 85A induces Th-1 immune responses in systemic sarcoidosis. AB - Sarcoidosis is a granulomatous disease of unknown etiology, characterized by a Th 1 immunophenotype. Although humoral immune responses by sarcoidosis subjects to mycobacterial proteins have been detected, mycobacterial antigens capable of inducing cellular immune responses in sarcoidosis subjects have not been reported. We used the enzyme-linked immunospot assay to assess for recognition of the Mycobacterium tuberculosis mycolyl transferase, Antigen 85A, by peripheral blood mononuclear cells from 25 sarcoidosis subjects, 22 PPD- (purified protein derivative) healthy volunteers, and 16 PPD+ healthy subjects. Reactivity to Ag85A whole protein was observed in 15 of 25 sarcoidosis subjects compared to 2 of 22 PPD- subjects (p=0.0006, Fisher's exact test) and to 14 of 16 PPD+ subjects (p=0.084, Fisher's exact test). Monoclonal antibody against HLA-DR inhibited recognition. In addition to immune recognition of Ag85A whole protein, peptide mapping studies identified four immunogenic Ag85A peptides, which induced Th-1 immune responses in individual sarcoidosis subjects, suggesting that multiple epitopes from a mycobacterial protein may have a role in sarcoidosis immunopathogenesis. PMID- 17357847 TI - Unexpected immunoresponse to Gal and APA antigens in diabetic type 1 patients receiving neonatal pig islets after 6 years. AB - Cotransplantation of porcine islets and Sertoli cells into preimplanted subcutaneous devices improve metabolic control in type 1 diabetic patients, and survive grafted for more than 4 years. We report here, further assessment of the endocrine and porcine nature of the surviving cells and the immune responses elicited toward Gal alpha(1,3)-Gal beta(1,4)-GlcNAc (Gal) antigen in patients who received a second and third transplants. No immunosuppressive drugs were administered. We were able to immunostain insulin- and glucagon-positive cells in all biopsies of patients and Sertoli cell markers in 60.9% of biopsies. Additionally, all biopsies tested, amplified the porcine COII gene. Patients demonstrated an increase in antipig antibodies in response to the first transplant with a decreasing response toward the second and third transplants. In all transplants, the IgG levels promptly returned to basal values after 3-4 months. The long-term survival of porcine cells and the reduced humoral immune response to multiple transplants indicate a form of tolerance. We have not been able to find CD25-positive cells, indicating that it is probably an immune accommodation of the graft. PMID- 17357848 TI - A status report from 1996-2004: are more effective immunization interventions being used in the women, infants, and children (WIC) program? AB - BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) enrolls almost 50% of the US birth cohort and these children have significantly lower immunization coverage rates than their counterparts not eligible for WIC. In 1994, the Centers for Disease Control and Prevention (CDC) and USDA began a national initiative to increase immunization coverage in low income children by incorporating immunization-promoting activities into WIC visits (WIC/Immunization linkages). Since 1998, CDC has monitored the WIC/Immunization linkages assessment and referral (with and without the more aggressive strategy of monthly voucher pick-up, client outreach and tracking and parental incentives) and three other immunization supporting activities (computerized systems to assess immunization status, collocation of WIC and immunization services, coordination of WIC and immunization services). METHODS: Through an annual survey of state Immunization and WIC programs, a trend analysis was conducted for years 1998 through 2004 to determine changes in the use and frequency of WIC/Immunization linkage activities. RESULTS: During the 7-year study period, the use of assessment and referral increased from 71% to 94%, monthly voucher pick-up from 24% to 35%, and coordination of WIC and immunization services from 61% to 78% (p<0.0001 for all comparisons) in WIC sites nationwide. The frequency of assessment and referral (at each visit [four or more times/ year] versus certification visits [two times/year]) was reported to decrease during the study period (p<0.0001). Outreach and tracking and collocation of services did not change significantly while the use of parental incentives decreased (p<0.0001). The availability of computers and their use immunization assessment increased during the period. From 2002-2004, the number of states reporting that they base assessment and referral on a single vaccine (diphtheria tetanus-acellular pertussis) instead of counting multiple vaccines increased from 5 to 10. CONCLUSIONS: Immunization promoting activities, especially those known to be most effective in improving coverage such as monthly voucher pickup, are increasing in WIC. Focusing on effective interventions including supporting activities such as computerized assessment will be essential in meeting Healthy People 2010 infant and childhood immunization coverage goals. In addition, the use of WIC resources can be minimized by encouraging evaluation of diphtheria tetanus-acellular pertussis coverage as a marker for up to date status, instead of counting all vaccine doses. PMID- 17357849 TI - Intraurban variations in adult mortality in a large Latin American city. AB - Urbanization is high and growing in low- and middle-income countries, but intraurban variations in adult health have been infrequently examined. We used spatial analysis methods to investigate spatial variation in total, cardiovascular disease, respiratory disease, and neoplasm adult mortality in Buenos Aires, Argentina, a large city within a middle-income country in Latin America. Conditional autoregressive models were used to examine the contribution of socioeconomic inequalities to the spatial patterning observed. Spatial autocorrelation was present in both men and women for total deaths, cardiovascular deaths, and other causes of death (Moran's Is ranging from 0.15 to 0.37). There was some spatial autocorrelation for respiratory deaths, which was stronger in men than in women. Neoplasm deaths were not spatially patterned. Socioeconomic disadvantage explained some of this spatial patterning and was strongly associated with death from all causes except respiratory deaths in women and neoplasms in men and women [relative rates (RR) for 90th vs 10th percentile of percent of adults with incomplete high school and 95% confidence intervals: 1.23 and 1.09-1.39 vs 1.24 and 1.08-1.42 for total deaths in men and women, respectively; 1.36 and 1.15-1.60 vs 1.22 and 1.01-1.47 for cardiovascular deaths; 1.21 and 0.97-1.52 vs 1.07 and 0.85-1.34 for respiratory deaths; 0.94 and 0.85 1.04 vs 1.03 and 0.87-1.22 for neoplasms; and 1.49 and 1.20-1.85 vs 1.63 and 1.31 2.03 for other deaths]. There is substantial intraurban variation in risk of death within cities. This spatial variability was present for multiple causes of death and is partly explained by the spatial patterning of socioeconomic disadvantage. Our results highlight the pervasive role of space and social inequalities in shaping life and death within large cities. PMID- 17357850 TI - Full of sound and fury, signifying something: the impact of autonomic arousal on EGM gambling. AB - An experiment was conducted to observe the influence of autonomic arousal on subsequent gambling behavior. Thirty-seven male and 32 female regular Electronic Gaming Machine (EGM) players were recruited through newspaper advertisements. Participants were randomly assigned to either: (1) a control condition, or (2) an experimental condition that introduced a loud white-noise event (80 db) at fixed 120 s intervals throughout the 5-min EGM gambling session. Galvanic Skin Response (GSR) measurements showed that the manipulation was successful in elevating autonomic arousal. The results showed differences in behavioral response to the manipulation based on prior experience with gambling problems. Persons with many gambling problems had lower average bet-sizes in the white-noise condition compared to the control, while those with few or no problems had higher average bet-sizes. The results suggest that arousal may provide different signals to gamblers with few versus many problems. Gamblers with many problems may interpret their arousal as a sign that they will soon lose money, while gamblers with few or no problems may associate feelings of arousal exclusively with winning. PMID- 17357851 TI - Group and organizational involvement among persons with psychiatric disabilities in supported housing. AB - This study examined the patterns and correlates of group and organizational involvement among persons with psychiatric disabilities using a cross-sectional, probability sample of 252 residents in supported independent housing (SIH). Groups and organizations were classified according to whether or not they have a behavioral health focus. Demographic, clinical, and service use characteristics were examined as potential predictors of membership using Poisson regression models. Findings indicated that 60% of the sample was involved in some kind of behavioral or nonbehavioral health organization. Similar to the findings from the general population, higher rates of membership were found among older persons, Blacks, those with more years of education, and those with higher incomes. Other correlates specific to the SIH sample included prior homelessness, perceived discrimination, substance abuse history, psychiatric symptoms, psychiatric diagnosis, and contact with service providers. Implications of study findings for developing intervention strategies to enhance organizational membership and for future research are discussed. PMID- 17357852 TI - Mental health benefits in Employer-sponsored Health Plans, 1997-2003. AB - Data drawn from the Mercer National Survey of Employer-sponsored Health Plans in 1997 and 2003 indicate that a large majority of employers continue to provide some level of coverage for mental health (MH) services in their primary plans. However, a majority of plans continue to impose different benefit limitations for MH than for other medical treatment. Among plans with limitations on MH coverage, there was a sharp increase in the use of limits on inpatient days and outpatient visits between 1997 and 2003. The proportion of employers providing coverage for some MH services decreased; e.g., among small employers, 88% provided coverage for inpatient MH care in 2003, compared with 94% in 1997. These results suggest that parity legislation has had a noticeable but limited effect, but that, at least in the short-term, it is unlikely that universal parity in employer-based plans will be achieved through a legislative strategy. PMID- 17357855 TI - Detection of first relapse in cutaneous melanoma patients: implications for the formulation of evidence-based follow-up guidelines. AB - BACKGROUND: The value of follow-up surveillance for patients with cutaneous melanoma remains uncertain. In this prospective study the frequency of detection of first melanoma recurrence (FMR) by patient or doctor was analyzed to assist in the future design of evidence-based follow-up guidelines. METHODS: Patients who had a recurrence of a previously treated American Joint Committee on Cancer (AJCC) stage I-III primary melanoma (PM) were interviewed to ascertain how their PM and FMR were detected. Factors predicting the detection of PM and FMR were analyzed. RESULTS: The study group comprised 211 patients. In 168 patients, information on detection of their PM was available; 102 PMs (61%) were detected by the patient and 18 (11%) by their partner. Higher AJCC stage, visible location for the patient, and female sex were independent predictive factors for patient detected PM (P = .03, .002, and .02 respectively). The FMR type was local in 28 (13%), in transit in 35 (17%), in regional lymph nodes in 97 (46%), and distant in 51 (24%). Seventy-three percent of all FMRs were detected by the patient. The presence of a symptom was the only independent predictor of a patient-detected FMR (P < .0001). There was no statistically significant survival difference between the patient-detected and doctor-detected FMRs. CONCLUSIONS: Three quarters of FMRs were detected by patients or their partners, and it should be possible to improve this rate even further by better education. More frequent follow-up visits are thus unlikely to be valuable. Reductions in follow-up frequency may therefore be safe and economically responsible. PMID- 17357856 TI - Clinical correlation of endoscopic ultrasonography with pathologic stage and outcome in patients undergoing curative resection for gastric cancer. AB - BACKGROUND: Endoscopic ultrasonography (EUS) is considered valuable for preoperative staging of gastric cancer and defining patient eligibility for enrollment in neoadjuvant protocols. The aim of this study was to correlate EUS staging with pathologic evaluation and outcome in patients undergoing curative R0 resection for gastric cancer. METHODS: All patients who underwent preoperative clinical assessment of T/N stage with EUS and subsequent R0 resection for gastric adenocarcinoma between 1993 and 2003 were identified from a prospective database. Patients who received neoadjuvant chemotherapy were excluded. Clinical staging results from preoperative EUS were compared with postoperative pathologic staging results and correlated with clinical outcome. RESULTS: Two hundred twenty-five patients with gastric cancer underwent EUS followed by R0 resection, without preoperative chemotherapy. The accuracy of the individual EUS T stage was 57% (127 of 223) and was 50% for N stage (110 of 218). Although EUS was less able to predict outcome according to individual T stage, patients with lesions or=T3. Preoperative assessment of risk was not predicted by EUS N stage alone. Patients identified as high risk on EUS and those with a combination of serosal invasion and nodal disease had both the highest concordance with pathology and a significantly worse outcome (P = .02). CONCLUSIONS: The concordance between EUS and pathologic results was lower than expected for individual T and N stages. Patients with lesions -A, -B > -E. Liv-SGP-G was the most abundant CHH-family peptide in the sinus gland and showed strong vitellogenesis-inhibiting activity. As a result of detailed structural analysis, its complete primary structure was determined; it consisted of 72 amino acid residues and possesses an amidated C-terminus. PMID- 17357859 TI - Stapled transanal rectal mucosectomy ten years after. AB - Stapled mucosectomy (SM) was first proposed for the management of patients with rectal internal mucosal prolapse and obstructed defecation, but gained popularity worldwide for the treatment of hemorrhoids. The present review highlights the advantages and disadvantages of the operation. SM tends to decrease postoperative pain and shortens convalescence after hemorrhoid surgery, but may be followed by severe complications, e.g. rectal obliteration and pelvic sepsis requiring a diverting stoma, more frequently than after standard hemorrhoidectomy. Moreover it carries a higher recurrence rate in the treatment of fourth-degree piles. A recent Cochrane metaanalysis demonstrated that SM is less effective than standard hemorrhoidectomy since it carries a higher recurrence rate (OR=3.6) and reintervention rate (OR=2.3). When used for rectal mucosal prolapse and obstructed defecation, SM is reported to have variable results. A better outcome is likely to be achieved in patients without anismus and psychoneurosis operated on by specialists trained with this technique. PMID- 17357861 TI - Long-term results show triple stapling facilitates safe low colorectal and coloanal anastomosis and is associated with low rates of local recurrence after anterior resection for rectal cancer. AB - BACKGROUND: During low anterior resection (AR), placement of a staple line distal to an occlusion clamp is often difficult due to the confines of a narrow bony pelvis. This study reviewed the results of AR with a technique in which a linear staple line is fired below the tumour as an oncologically safe occlusion clamp. METHODS: Between 1995 and 2000, a total of 174 patients were operated for rectal cancer, and 153 of these patients had AR. Triple stapling (TS) was used to place a line of staples that occluded the fully mobilised rectum below a tumour. After rectal washout, a further linear stapler was applied below the first, and the rectum was divided prior to a standard circular stapled anastomosis. RESULTS: TS was performed in 127 (83%) of 153 patients undergoing AR, and 9 TS patients developed leaks (7%). In the whole series of 174 cases, 9 patients had local recurrence (5%), but the local recurrence rate for procedures classified as 'locally curative' was 2%. CONCLUSIONS: Triple stapling reliably occludes the rectum allowing for distal rectal washout. It eliminates clamp slippage and faecal spillage and improves access to the distal rectum for low anastomoses. PMID- 17357860 TI - Novel colorectal endoscopic in vivo imaging and resection practice: a short practice guide for interventional endoscopists. AB - Colorectal cancer remains a leading cause of cancer death in the UK. With the advent of screening programmes and developing techniques designed to treat and stage colorectal neoplasia, there is increasing pressure on the colonoscopist to keep up to date with the latest practices in this area. This review looks at the basic principles behind endoscopic mucosal resection and forward to the potential endoscopic tools, including high-magnification chromoscopic colonoscopy, high frequency miniprobe ultrasound and confocal laser scanning endomicroscopic colonoscopy, that may soon become part of routine colorectal cancer management. PMID- 17357862 TI - Impact of fibrin sealant on Limberg flap technique: results of a randomized controlled trial. AB - BACKGROUND: Pilonidal disease is a common chronic disorder mainly seen in the sacrococcygeal region, especially in young males. Different surgical methods have been described for the treatment. Limberg flap has low morbidity and recurrence rates. Fibrin sealant, a two-component tissue adhesive composed of fibrinogen and thrombin, has been used in a number of surgical procedures to achieve hemostasis and to seal tissues. The purpose of this study was to investigate the impact of fibrin sealant on the Limberg flap procedure. METHODS: Between January 2003 and January 2004, 32 male patients with pilonidal disease were randomly assigned to receive the standard Limberg flap technique (n=16) alone or with fibrin sealant application (n=16) before drain insertion. RESULTS: The two groups were similar for age and body mass index. The total drainage volume was 64.4+/-28.0 ml in the control group and 16.2+/-13.6 ml in the fibrin sealant group (p<0.001). Moreover, hospitalization time was 3.9+/-0.6 days in the control group and 2.0+/-0 days in the fibrin sealant group (p<0.001). CONCLUSIONS: Use of fibrin sealant for Limberg flap technique shortens hospitalization time, reduces drainage volume and is therefore recommended. PMID- 17357863 TI - Anal endosonography: a survey of equipment, technique and diagnostic criteria adopted in nine Italian centers. AB - BACKGROUND: Anal endosonography (AES) has become an essential part of the pre operative diagnostic workup in both organic and functional anal diseases. METHODS: Nine Italian centres with an average volume activity of >10 exams/week each were surveyed with the aim of determining the concordance with respect to indications for the procedure and interpretation of the results. RESULTS: Overall, anal sepsis, faecal incontinence and anorectal tumours were the more common indications for AES while evacuation dysfunctions and anal pain were not always considered indications. All centres use the same diagnostic criteria for simple and complicated perirectal sepsis and sphincteric defects, but adopt different classifications for stage 1 and stage 2 anal tumours. Participants agreed in that lymph-node staging by AES is less precise than tumour staging, especially after chemoradiation therapy. CONCLUSIONS: A list of recommendations and guidelines based on the groups's experience has been produced for those radiologists and coloproctologists interested in the use of AES and accreditation of their centres. PMID- 17357864 TI - Perianal mucinous adenocarcinoma arising from chronic anorectal fistulae: a review from a single institution. AB - BACKGROUND: Mucinous adenocarcinoma arising from a chronic anorectal fistula is rare, with few reports in the literature. Such lesions present in an innocuous manner and can be mistaken for the more common clinical condition of a benign perianal abscess or fistula. METHODS: From our prospectively collected database, we identified 4 patients with chronic perianal inflammatory conditions who were subsequently found to have developed perianal mucinous adenocarcinoma on biopsy. We received the symptomatology, subsequent management and further follow-up of each patient. These patients were treated with radical surgery, with or without adjuvant therapy. RESULTS AND CONCLUSIONS: A high index of clinical suspicion is required to make the diagnosis of perianal tumours while assessing patients presenting with perianal inflammatory conditions. Wide excision of the tumour with abdominoperineal resection is the surgical treatment of choice and can provide good long-term results in patients with localized disease. PMID- 17357865 TI - Rectal cooling test in the differentiation between constipation due to rectal inertia and anismus. AB - BACKGROUND: The differentiation between constipation due to rectal inertia and that due to outlet obstruction from non-relaxing puborectalis muscle (PRM) is problematic and not easily achieved with one diagnostic test. Therefore, we studied the hypothesis that the rectal cooling test (RCT) can effectively be used to differentiate between those two forms of constipation. METHODS: The study enrolled 28 patients with constipation and abnormal transit study in whom radio opaque markers accumulated in the rectum; 15 healthy volunteers acted as controls. Electromyographic activity of the external anal sphincter (EAS) and PRM was initially recorded. Subsequently rectal wall tone was assessed by a barostat system during rectal infusion with normal saline at 30 degrees C and at 4 degrees C with simultaneous electromyography (EMG). RESULTS: There was a significant increase in EMG activity of the EAS and PRM on strain- ing (p<0.001), suggestive of anismus, in 10 of 28 patients and 0 of 15 controls. Rectal tone in controls did not respond to saline infusion at 30 degrees C, but it increased at 4 degrees C (p<0.05). Similarly, in constipated patients rectal tone did not respond to rectal saline infusion at 30 degrees C, but infusion at 4 degrees C increased tone in all 10 patients with anismus (p<0.05); EMG activity of the EAS and PRM also increased (p<0.001). In the remaining 18 patients, rectal tone after saline infusion at 4 degrees C remained unchanged. CONCLUSIONS: Rectal infusion with iced saline increased rectal tone in healthy controls and constipated patients with anismus while it had no effect in the remaining patients. Lack of increase of rectal tone may be secondary to rectal inertia. According to these preliminary observations, the rectal cooling test may be useful in differentiating between rectal inertia and anismus. PMID- 17357866 TI - Useful parameters helping proctologists to identify patients with defaecatory disorders that may be treated with pelvic floor rehabilitation. AB - BACKGROUND: No studies have specifically reported on the use of a diagnostic tool based on physiatric assessment of constipated or incontinent patients METHODS: Sixty-seven constipated and 37 incontinent patients were submitted to a standard protocol based on proctologic examination, clinico-physiatric assessment (puborectalis contraction, pubococcygeal test, perineal defence reflex, muscular synergies, postural examination) and instrumental evaluation (anorectal manometry, anal US and dynamic defaecography). Patients were offered pelvic floor rehabilitation (thoraco-abdominoperineal muscle coordination training, biofeedback, electrical stimulation and volumetric rehabilitation). RESULTS: After rehabilitation treatment, decreases of Wexner constipation score (p=0.0001) and Pescatori incontinence score (p=0.0001) were observed. CONCLUSION: This diagnostic protocol might improve the selection of patients with defaecatory disorders amenable for rehabilitation treatment. PMID- 17357867 TI - The cleansing result of oral sodium phosphate is inversely correlated with time between the last administration and colonoscopy. AB - BACKGROUND: There is some evidence that the timing of sodium phosphate (NaP) ingestion affects the cleansing result. The objective of this study was to evaluate the correlation of cleansing result with the timing of ingestion of NaP. METHODS: 214 consecutive outpatients scheduled to undergo colonoscopy were enrolled in the study. All patients filled out a detailed questionnaire concerning the execution of bowel cleansing. Concomitant with colonoscopy, patient characteristics were recorded and after the procedure the cleansing result was scored. The correlation between cleansing score and time from the last dose of NaP to colonoscopy was evaluated. For further analysis, patients were divided into three groups regarding the time lag from NaP taking to colonoscopy (group 1, 6 h or less; group 2, 6-12 h; group 3, 12 h or more). RESULTS: 204 patients had complete colonoscopy and enough data to be analyzed for the study. The Pearson correlation coefficient for the time between the last dose of NaP and colonoscopy was -0.450 (p=0.0001) showing an inverse correlation. The mean cleansing score (+/-SEM) of group 1 was 4.00+/-0.12, for group 2 it was 3.56+/ 0.12, and for group 3 it was 2.64+/-0.14. There were statistically significant differences between all groups. CONCLUSION: The cleansing result of NaP is inversely correlated with the time between last dose of NaP and colonoscopy. Colonoscopy should be preferably performed within 12 hours of taking the second dose of NaP. PMID- 17357868 TI - Concurrent laparoscopic right hemicolectomy and ultra-low anterior resection with colonic J-pouch anal anastomosis for synchronous carcinoma. AB - An extensive large bowel resection with a single anastomosis is the accustomed management option for widely spaced synchronous colorectal neoplasms. We report a successful case of concurrent laparoscopic right hemicolectomy and ultra-low anterior resection with colonic J-pouch anal anastomosis in an 85-year-old man with synchronous cancers of the hepatic flexure and lowrectum. This surgical technique is advantageous for elderly patients as it provides the benefits of multiple segmental resection and laparoscopic surgery while potentially reducing mortality, time of procedure, postoperative pain, ileus, length of hospitalization and direct cost of care, and improving independence at discharge. The technique for efficient multiple extractions of specimens and effective reconstitution of pneumoperitoneum for a multistaged procedure is discussed. PMID- 17357869 TI - A novel technique for nonoperative removal of round rectal foreign bodies. AB - Extraction of rectal foreign bodies is challenging. The medical literature confirms the diversity of the problem and equally some ingenious solutions, the majority of which requires either an anesthetic agent or a laparotomy to remove them. This case report presents a simple nonoperative technique to deal with one such situation. PMID- 17357870 TI - Hereditary internal anal sphincter myopathy: the first Caribbean family. AB - Hereditary proctalgia is an extremely rare condition characterized by endosonographic evidence of internal anal sphincter (IAS) thickening and specific ultrastructural changes seen at light and electron microscopy (EM). We report the case of a 54-year-old Caribbean woman with severe proctalgia and IAS thickening, treated with IAS myectomy. Transmission EM showed PAS-positive inclusions and granulofibrillary smooth muscle inclusion bodies. Anal endosonography of 5 family members from 3 generations showed IAS thickening in all cases with reported proctalgia. The condition represents an isolated IAS myopathy which is a probable polysaccharide storage disease variant. This condition may require specific surgical therapy with specimen preservation and ultrastructural examination for optimal characterization and treatment. PMID- 17357871 TI - Endoscopic management of postoperative stapled colorectal anastomosis hemorrhage. AB - Rectal bleeding following colorectal anastomosis is common but usually self limited. Continuous hemorrhage is rare, and when it occurs, often requires further treatment. The most frequently used strategies for treatment of stapled anastomotic hemorrhage are clinical observation with or without blood transfusion, rectal packing, angiographic identification of the bleeding site with vasopressin infusion or embolization, and endoscopic eletrocoagulation. We report the case of a 49-year-old man with uncomplicated diverticular disease who was treated by laparoscopic sigmoidectomy, with double-stapled colorectal anastomosis. Six hours later, the patient presented intense rectal bleeding and was taken to the operation room for urgent colonoscopic examination. After complete removal of blood clots inside the rectum, a bleed localized at the anastomotic site was identified and submucosal peri-anastomotic injection of 10 ml adrenaline (1:200 000) in saline was performed with immediate bleeding control. PMID- 17357872 TI - Long-term results after transanal stapled excision of rectal internal mucosal prolapse. PMID- 17357874 TI - Sir W. Ernest Miles. PMID- 17357876 TI - Is there a role for concomitant pelvic floor repair in patients with sphincter defects in the treatment of fecal incontinence? PMID- 17357877 TI - Large iatrogenic colonic perforation repaired endoscopically with Triclip. PMID- 17357878 TI - Serum levels of sL-selectin and tumour necrosis factor-alpha in children with type 1 diabetes mellitus. AB - Type 1 diabetes mellitus (DM) is a result of inflammation and destruction of alpha-cells in the pancreatic islet cells. The aim of this study is to evaluate the associations of diabetes with soluble L-selectin (sL-selectin) and tumour necrosis factor-alpha (TNF-alpha) in children with type 1 DM; and also to evaluate the associations of these parameters with the disease period, glycaemic control state and puberty stage. Serum sL-selectin and TNF-alpha levels were measured in 44 children with type 1 DM and 44 healthy children. Neither the patients nor the control group showed significant difference between the levels of sL-selectin and TNF-alpha (sequence mean 12.17+/-1.62 ng/ml vs. 12.62+/-1.56 ng/ml and 7.27+/-3.1 pg/ml vs. 7.88+/-2.7 pg/ml). There was no statistically significant difference between children with duration of diabetes longer than 5 years and children with duration of diabetes shorter than 1 year. There was also no statistically significant difference between poor glycaemic control and good acceptable glycaemic control patients. The present results indicate that sL selectin and TNF-alpha serum levels are not increased and cannot be used as prognostic predictors in type 1 DM; and also sL-selectin and TNF-alpha do not change with the disease period, glycaemic control state and puberty stage. PMID- 17357879 TI - M-cadherin, a candidate gene for type 2 diabetes and related phenotypes in a KK/Ta mouse model. AB - The KK/Ta strain serves as a suitable polygenic mouse model for type 2 diabetes associated with fasting hyperglycaemia, glucose intolerance, hyperinsulinaemia, mild obesity and dyslipidaemia. Recently, we reported the susceptibility loci contributing to type 2 diabetes and related phenotypes in KK/Ta mice. In the present study, to identify susceptibility genes for type 2 diabetes and related disorders, GeneChip Expression Analysis was employed to survey the gene expression profile in the liver of KK/Ta and BALB/c mice. M-cadherin, a calciumdependent intercellular adhesion molecule, showed increased expression in the liver of KK/Ta mice, and sequence analysis revealed three missense mutations. The relationship between these polymorphisms and various phenotypes in 208 KK/Ta x (BALB/c x KK/Ta) F1 backcross mice was analysed. Statistical analysis revealed that M-cadherin exhibits linkage to levels of triglyceride and insulin in sera, glucose tolerance and body weight. Although it has been postulated that M cadherin may be important for the regulation of morphogenesis of skeletal muscle cells, these results suggest that M-cadherin may influence hypertriglyceridaemia, glucose intolerance, hyperinsulinaemia and obesity in KK/Ta mice. PMID- 17357880 TI - Major childhood infectious diseases and other determinants associated with type 1 diabetes: a case-control study. AB - The objective of the study was to evaluate the association between infectious diseases and other events pertaining to childhood medical history and type 1 diabetes. A case-control study was carried out, taking as cases 159 type 1 diabetic patients (0-29 years) recorded from 1988 to 2000 within the population registry of the Pavia province (North Italy). As controls 318 non-diabetic subjects were matched by age and sex. A questionnaire was administered by standardised interviewers. Data were analysed by conditional logistic regression. Viral childhood diseases (OR 4.29; 95%CI 1.57-11.74) and bottle feeding (OR 1.83; 95%CI 1.08-3.09) were directly correlated to type 1 diabetes; an inverse correlation was found for vitamin D administration during lactation (0-14 years) (OR 0.31; 95%CI 0.11-0.86) and for history of scarlet fever in both sexes and age groups (OR 0.19; 95%CI 0.08-0.46). Most associations of the studied variables confirm already known findings. The significant inverse correlation of type 1 diabetes with scarlet fever history is a peculiar finding, the meaning of which is still obscure, although it has been recently described that streptococcal A infections are regulated by HLA class II alleles. PMID- 17357881 TI - Measurement of salivary adiponectin levels. AB - We designed a method for measuring salivary adiponectin. In 188 healthy males, salivary adiponectin levels were measured using a commercial enzyme immunoassay kit for plasma with minor modifications. Intra- and inter-assay coefficients of variation for salivary adiponectin ranged from 0.6 to 4.9 and 1.1 to 9.8%, respectively. Salivary adiponectin levels ranged from 0.37 to 6.42 ng/ml, exceeding the kit's detection limit. For the over-43 age group, there was a significant correlation between plasma and salivary adiponectin levels (p<0.000001). These findings suggest the possibilities of salivary adiponectin as a marker of increased risk of non-insulin-dependent diabetes mellitus or cardiovascular disease. PMID- 17357882 TI - Effect of a variable hepatic insulin clearance on the postprandial insulin profile: insights from a model simulation study. AB - The liver plays a pivotal role in determining postprandial insulin levels because it is responsible for the extraction of a large (approximately 50%) fraction of the newly secreted insulin by the pancreas. Evidence exists that hepatic insulin extraction is not constant during a meal, but is inhibited because of saturable receptor-mediated mechanisms and/or increase in hepatic blood flow. The aim of the present study was to exploit the ability of mathematical model simulation to shed light on the role of a variable hepatic insulin extraction during a meal. Mathematical models of insulin secretion and kinetics were coupled to provide predictions for the concentration of insulin in plasma following a meal under the assumptions of either a constant or a time-varying hepatic insulin clearance. Our results indicate that a 20% inhibition in hepatic clearance is able to remarkably enhance the plasma insulin level following a meal. These results emphasise the need for simple and accurate methods to measure the time course of hepatic insulin extraction under nonsteady-state conditions. PMID- 17357884 TI - Outcome of pregnancy in women with type 1 diabetes intensively treated with continuous subcutaneous insulin infusion or conventional therapy. A case-control study. AB - The aim was to evaluate and compare the outcome of pregnancies of women with type 1 diabetes (T1D) intensively treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Twenty-nine women with T1D receiving CSII during pregnancy as intensive insulin therapy (27 started CSII during pregnancy planning while 2 started CSII during the 1st month of gestation) were matched for age, duration of T1D, White's classification, BMI before gestation, parity and HbA1c before pregnancy with 29 women treated with MDI. Metabolic control and acute complications were registered including ketoacidosis and severe hypoglycaemic episodes, and the development of hypertension induced by pregnancy and pre-eclampsia. Perinatal mortality, stillbirth, minor and major congenital malformations, macrosomia, weeks at delivery, caesarean section and perinatal complications were also recorded. As expected, there were no differences between the two groups in terms of age, duration of the disease, White's classification, BMI before gestation, parity and HbA1c before pregnancy. The proportion of subjects who received preconceptional guidance and planned pregnancy did not differ between groups. No differences were observed in HbA1c, insulin dose and BMI throughout gestation in either group of patients. Maternal, foetal and perinatal outcome were similar in women treated with CSII or MDI. The use of CSII in pregestational T1D women is associated with similar results in metabolic control, maternal, foetal and perinatal outcome during pregnancy to those obtained using MDI. PMID- 17357883 TI - The association between type 2 diabetes mellitus and A1/A2 polymorphism of glycoprotein IIIa gene. AB - Glycoprotein IIIa (GpIIIa) is a membrane receptor, found in various tissues, that has two alleles: A1 and A2. Signalling cascade of GpIIIa is modulated by enzymes called calpains, proteases that may also influence glucose metabolism. There is one small study that shows a high association of A1/A2 polymorphism with type 2 diabetes mellitus. In our research we planned to evaluate the association of A1/A2 polymorphism with type 2 diabetes in a population of patients with ST elevation acute myocardial infarction (STEMI). The study comprised 352 individuals. From the cohort of patients hospitalised for STEMI we chose 113 patients with diagnosed diabetes (diabetic group) and 118 patients with STEMI and normal glucose metabolism (non-diabetic group). The population group consisted of 121 persons. Genotyping was performed by the restriction fragments length polymorphism (RFLP) method. The frequency of alleles in all groups was in Hardy Weinberg equilibrium. The percentage of A2 allele carriers was comparable among all groups : 20.4% (diabetic patients), 23.7% (nondiabetic) and 21.5% (control group) (p>0.05). There was no significant difference in frequency of A2 allele among the groups. We have not observed any association between GpIIIa polymorphism with either type 2 diabetes or STEMI. PMID- 17357885 TI - The effect of diabetes and centrally administered insulin on anterior hypothalamic estrogen receptor alpha immunoreactivity. AB - Diabetic rats have characteristic reproductive deficits. Peripheral and central (intra-cerebro-ventricular [ICV]) insulin restores the reproductive phenotype to control levels. In this experiment, we evaluated a possible defect in steroid feedback by evaluating hypothalamic estrogen receptor (ER) alpha availability using ERalpha immunocytochemistry. Animals were ovariectomised and given estradiol and progesterone. Diabetic and control animals were given ICV insulin or saline. Nuclear and/or cytoplasmic ERalpha immunoreactivity was evaluated in the paraventricular nucleus (PVN) and the organum vasculosum laminae terminalis (OVLT). In the PVN, nuclear immunoreactivity was increased among diabetic, ICV insulin-treated animals. Diabetic saline-treated and nondiabetic animals had similar ERalpha immunoreactivity. The OVLT had lower numbers of immunoreactive neurons compared to the PVN; no differences among the treatment groups were found in the OVLT. Central insulin treatment increased the number of PVN nuclear ERalpha immunoreactive neurons among diabetic animals. However, there was no reduction in ERalpha when comparing saline-treated diabetic animals to non diabetic rats, suggesting that decreases in hypothalamic ERalpha in the regions studied do not account for diabetes-induced reproductive deficits. PMID- 17357886 TI - [Stem cell potential uses in retinal dystrophies]. PMID- 17357887 TI - [A molecular marker for dry eye]. PMID- 17357888 TI - [Adalimumab therapy for Vogt-Koyanagi-Harada syndrome]. PMID- 17357889 TI - [Octreotide scintigraphy in thyroid orbitopathy]. AB - INTRODUCTION: Graves' disease, which has an autoimmune basis, is associated with the infiltration of activated lymphocytes into the retrobulbar tissues of the eye. These activated lymphocytes express somatostatin receptors on their surface which mediate the inflammatory response. OBJECTIVE: To evaluate the efficiency of (111) In-Octreotide scintigraphy in the identification of orbital activity in Graves' disease and the usefulness of treatment with a somatostatin analogue, based on a pre-established protocol within the Nuclear Medicine Department. METHODS: We studied a group of eighteen patients with symptomatic Graves' ophthalmopathy of between two months and four years duration. We injected 6 mCi of (111) In-Octreotide parenterally, and performed scintigraphy four and twenty four hours later. Four patients, all in the active phase, showed orbital somatostatin receptors, for which they were treated with lanreotide 60 mg every fifteen days for three months. Patients were reviewed after 3 months treatment with a further scintigraphy and clinical study. RESULTS: In our study all four treated patients had less than sixteen months of ophthalmopathy, and three responded well to the treatment. CONCLUSION: Scintigraphy with Octreotide is a useful procedure allowing identification of patients in the active phase of the ophthalmopathy who are likely to respond well to treatment with somatostatin analogues. PMID- 17357890 TI - [Measurement of lens density with a Scheimpflug camera in diabetic patients]. AB - OBJECTIVE: To assess if diabetes, in patients without cataracts or diabetic retinopathy, alters the densitometric values of the lens and to what degree this occurs. METHODS: A total of 93 patients, divided into two groups, were studied: the diabetic patients had a visual acuity equal to or greater than 0.8 and normal eye funduscopy, and the control group consisted of healthy patients of a similar age. Measurements in all patients were made with the Scheimpflug camera and the lens density of the anterior capsule, anterior cortex and nucleus was defined. The values obtained in the two groups were compared by analysis of variance (ANOVA). RESULTS: All densitometric values were greater in the diabetic patients than in the normal controls. The greatest difference was seen in the values of the anterior capsule, followed by the nucleus and cortex. The differences approached statistical significance (P=0.07) only in the case of the anterior capsule. CONCLUSIONS: Diabetes increases densitometric values of the anterior capsule and to a lesser degree of the anterior cortex. However, further studies are necessary to verify if this alteration is of significance. PMID- 17357891 TI - [Anesthesia for vitreoretinal surgery using a retrobulbar catheter technique]. AB - OBJECTIVE: To evaluate peroperative pain management using a flexible spinal anesthesia catheter introduced into the retrobulbar space which allows injections of local anesthetics for vitreoretinal surgery. METHODS: Twenty-five patients who underwent vitreoretinal surgery receiving retrobulbar anesthesia with 3.5 ml ropivacaine 0.75%. After injection, a catheter with spinal needle 22G x 1 1/2 (40 x 0.7 mm) was introduced to the retrobulbar muscle cone. The needle was withdrawn and the catheter was fixed. When the patient started to feel pain (grade 3 or higher), 2 ml ropivacaine 0.75% was administrated through the catheter during surgery or 2 ml ropivacaine 0.2% in the postoperative period. The catheter was removed 24- 48h later. RESULTS: During surgery, 1 patient (4%) received a re injection of 2 ml ropivacaine 0.75% because of pain. Three patients (12%) experienced pain of grade 3 or higher in the postoperative period and needed re injection of 2 ml ropivacaine 0.2%. Re-injections were an effective method to achieve analgesia. Adverse effects were not noticed. CONCLUSIONS: The retrobulbar catheter technique is a procedure which allows multiple re-injections of local anesthetics; it provides adequate analgesia during surgery and rapid, effective and safe postoperative pain management. PMID- 17357892 TI - [Prevalence of diabetic retinopathy in the city of Badajoz 2002 (Extremadura project to prevent blindness)]. AB - OBJECTIVE: To establish the prevalence of diabetic retinopathy (DR), types and risk factors in a diabetic population in the city of Badajoz. METHODS: A cross sectional study, with prospective data collection, was performed in 2002 on 762 randomly selected diabetic patients belonging to two Primary Care Centers. We evaluated age, gender, type, treatment, duration of diabetes and blood pressure levels. Two color fundus photographs were taken and ophthalmoscopy performed on both eyes. Data were analyzed using SPSS (11.5). RESULTS: The mean age of the patients was 66.2 (DS 11.4) years, 4.7% were type 1 diabetics, 29% were insulin treated and 52.8% had elevated blood pressure. Prevalence of DR was 29.8%, macular edema 1.4% and proliferative DR 4.8%. Multivariate analysis showed that patients with an evolution of between 5 and 10 years had a frequency 1.13 times higher (ORaj 1.13; IC 95% 0.68-1.88; p=0.648) than those of less than 5 years evolution, while those with more than 15 years evolution had a frequency 3.12 times higher (ORaj 3.12; IC 95% 1.85-5.26; p<0.001). Patients receiving treatment with oral antidiabetic agents had an RD prevalence 2.39 times higher (ORaj 2.39; IC 95% 1.21-4.74; p=0,012) than those treated with diet only. Patients treated with insulin had a 10.32 higher frequency (ORaj 10.32; IC 95% 5.07-21.00; p<0.001) than those treated with diet. CONCLUSIONS: 29.8% of the diabetic population in the city of Badajoz is affected by DR. Although this prevalence is lower than that observed in previous studies performed by the same team, further studies should be carried out to detect risk sub-groups to allow us to act to decrease such a high prevalence. PMID- 17357893 TI - [Have patients who go to the emergency department changed? Evolutive study for the years 1997 and 2005]. AB - OBJECTIVE: To study the change in number and profile of patients who came to the Emergency Department of a level 2 hospital with ophthalmic emergencies in the years 1997 and 2005. METHOD: Two groups of randomly selected patients who came to the Emergency Service on the same day in the years 1997 and 2005 were studied. The study focused on the following variables: number of visits per day, gender, age, time period, number of examinations done, diagnoses and type of treatment prescribed. Comparison of proportions was carried out with a confidence interval study and Chi Square Test. RESULTS: The statistically significant changes (p<0.05) were as follows: increase in number of patients seen; increase in the diagnosis of corneal foreign body (25%); decrease in the diagnosis of conjunctivitis (12%); increase in cases in which only one examination was done (19%); increase in frequency of visits between 6 p.m. and 9 p.m. and decrease between 9 a.m. and 12 p.m; reduced attendance of those of female gender (13%) and increase in the male gender (13%); increase in patients between the age of 31 and 40 years (9%); decrease in the use of treatments such as occlusion and epithelializing ointment (7% and 6% respectively); increase in use of analgesics (5%), artificial tears (5%) and NSAIDs (8%); increase in referral of patients to their primary care physician (17%) and decrease in ophthalmology check ups (34%). CONCLUSIONS: The number of ophthalmological emergencies has increased in the last eight years, especially in young male patients, with work-related disease, who came in the evening. Treatments such as the use of artificial tears have increased, and patients are sent to the primary care physician more often. PMID- 17357894 TI - [Bilateral optic nerve infiltration in acute lymphoblastic leukemia in remission]. AB - CASE REPORT: An 18-year-old male affected by acute lymphoblastic leukemia (ALL) after having reached complete remission after chemotherapy developed bilateral optic nerve infiltration. DISCUSSION: Infiltration of the optic nerve may appear as an isolated sign of extramedullary relapse of ALL months in advance of the hematologic relapse. PMID- 17357895 TI - [Traumatic Horner syndrome]. AB - CASE REPORT: We present a case of Horner's syndrome in a 33-year-old man who presented with ptosis and right pupil miosis after cervical trauma. Computed tomography revealed a tender haematoma in the neck, which was producing tracheal deformity and stenosis. DISCUSSION: Cervical trauma may damage the sympathetic pathway and result in Horner's syndrome. This may be a manifestation of a life threatening condition. PMID- 17357896 TI - [Ocular manifestations in Proteus syndrome]. AB - CASE REPORT: Congenital disfiguring malformations are rare and usually have a multifactorial aetiology. Here we report on the ocular manifestations seen in a patient with Proteus syndrome. The retina showed retinal dysgenesia, retinal pigmentary abnormalities and optic nerve hypoplasia. Other abnormalities included strabismus and high myopia. DISCUSSION: Proteus syndrome is a complex hamartomatous disorder defined by local overgrowth, subcutaneous tumours and various bone, cutaneous and/or vascular anomalies. The incidence of ocular malformations in Proteus syndrome is unknown, however a meticulous cranio-facial examination and a systematic study of the eye is required to improve the medical care of these patients. PMID- 17357897 TI - [Atypical ophthalmic findings in Susac syndrome]. AB - CASE REPORT: A 25-year-old woman with encephalopathy and sensorineural hearing loss was referred to us in order to confirm Susac syndrome, due to bilateral visual loss. Funduscopic examination revealed peripheral retinal microangiopathy. DISCUSSION: Susac syndrome is typically characterized by the clinical triad of encephalopathy, branch retinal artery occlusions, and hearing loss. In our case, ophthalmic findings were atypical. Interrupted vessels and microaneurisms accumulation in the peripheral retina of both eyes were observed. PMID- 17357898 TI - [George Berkeley (1685-1753) (III)]. PMID- 17357899 TI - [Punishment by blinding the offender]. PMID- 17357900 TI - [Mental health and performance of medical students with high and low test anxiety]. AB - About 10 % of students suffer from test anxiety to such an extent that treatment is warranted. The correlation of high test anxiety with other mental disorders and study success is rarely investigated. OBJECTIVE: Do students with high test anxiety differ from students with low test anxiety regarding mental health and success in their studies? METHODS: Out of 945 medical students of all semesters 115 test persons were selected which scored either very high or very low for test anxiety. They were subjected to a clinical interview and two personality tests (NEO-FFI, TAS-20). The analysed sample contained 109 men und women. RESULTS: Students with high test anxiety suffered in a much higher proportion from social anxieties. Also, specific isolated anxieties and other mental disorders appeared in this group more often. They had a higher score of neuroticism, lower scores of extraversion and conscientiousness and they consumed more medication. In the high test anxiety group were more long-term students than in the low test anxiety group. Only 7 % of the students with high test anxiety were in psychotherapeutic treatment. Study finances, family status, cultural and gender affiliation were without or of minor significance. CONCLUSIONS: Students with high test anxiety are to a significant extent compromised in their performance and emotional wellbeing. They most likely would benefit from a low threshold psychotherapeutic outreach program offered by the university focusing among others their social anxieties. PMID- 17357901 TI - [Neuroimaging and the neurobiology of obsessive-compulsive disorder]. AB - The following review is focusing on results of functional neuroimaging. After some introductory remarks on the phenomenology, epidemiology, and psychotherapy approaches of obsessive-compulsive disorders (OCD) the most important OCD-related brain regions are presented. Obviously, not only the prominent cortico-striato thalamo-cortical feedback loops are involved, as functional brain imaging studies tell us, but also other regions as the inferior parietal lobe, the anterior and posterior cingulate gyrus, insula, amygdala, cerebellum, and others. Subclassifications using factor-analysis methods support the hypothesis, that most important subtypes ("washing/contamination fear", "obsessions/checking", "symmetry/ordering", "hoarding") involve different, but partially overlapping brain areas. Stimulation paradigms in fMRI-research are commonly based on symptom provocation by visual or tactile stimuli, or on action-monitoring and error monitoring tasks. Deficits in action-monitoring and planning are discussed to be one of the basic dysfunctions of OCD. Finally, results of psychotherapeutic induced variations of brain activations in OCD are presented. PMID- 17357902 TI - [The Barbie-Matrix: effectiveness of a school-based German program for the primary prevention of anorexia nervosa developed for girls up to the age of 12]. AB - More than 25 % of the 12-year-old girls in Thuringia (Germany) show problematic eating behaviour as measured with the Eating-Attitudes-Test (EAT-26D), which corresponds to an increased risk for the development of anorexia nervosa or bulimia nervosa. This was the starting position of a controlled study using a pre post-design to check the effectiveness of a newly developed German program for the prevention of anorexia nervosa in girls ("PriMa"). 42 Thuringian schools (20 as treatment group) with 1006 girls participated in the pilot study, which lasted from September 2004 to July 2005. Program effectiveness was analysed with mostly standardized questionnaires at three times of measurement (before, after the intervention and at 3 months follow-up) referring to body related self esteem (FBeK), satisfaction with body shape (KEDS), eating behaviour (EAT-26D) and body related attitudes. The program was established in 9 x 90-minute lessons including interactive exercises and discussing especially developed posters that show scenes of a Barbie-doll's life including the reports of a patient suffering from anorexia. Significant improvements on all variables could be reached for the higher risk group (EAT-26D >/= 10 points; = 26,7 %). Mean values in the EAT-26D decreased 5 points at the average which is equivalent with 6.6 % of the EAT-26D range, reflecting a practically significant change effect. PMID- 17357903 TI - [Strategy and results of pneumatic compression following transfemoral catheterization]. AB - BACKGROUND AND OBJECTIVE: Transfemoral arterial access of catheterization requires a method of hemostasis that is always easily and quickly applicable, but also safe, inexpensive and comfortable for the patient. Current methods meet these requirements only in part. The pneumatic pressure-controlled FemoStop system has been described as straightforward and safe. But the conventional procedure has been to achieve primary hemostasis with FemoStop and then switch to a pressure bandage. We here present our method of using FemoStop alone for the entire duration of the compression and compare the results with those of manual compression. PATIENTS AND METHODS: The preferred methods of managing the arterial puncture site in our center were compared for two different periods. Group MC (manual compression) comprised 1,085 patients (mean age 63.310.5 years, 29.8% females) in whom manual compression had been applied followed by a pressure bandage. Group FS (pneumatic compression) comprised 1,087 consecutive patients (mean age 64.610.7%, 35.1% females) in whom pneumatic compression only had been applied. The incidence of pseudoaneurysms, a-v fistulas and bleeding requiring transfusion were compared. RESULTS: The incidence of pseudoaneurysms after diagnostic cardiac catheterization in the FS group was lower than in the MC group. In patients after an angioplasty the results were similar other than the time the patient has to remain in bed. The incidence of a-v fistulas was similar in the two groups. There was only one episode pf bleeding that required transfusion (MC group). A multivariate analysis indicated that female gender is an independent risk factor for the occurrence of pseudoaneurysms and a-v fistulas. CONCLUSIONS: The FemoStop system used by itself took less time than manual compression and was associated with a slightly lower risk of complications. PMID- 17357904 TI - [Metastasis of medullary plasmocytoma as the cause of acute cholecystitis]. AB - HISTORY AND ADMISSION FINDINGS: A 66-year-old man was found to have a medullary plasmocytoma the year before admission, after sustaining a pathological fracture of the femur. During treatment for sciatica his general condition deteriorated and he developed abdominal pain. Laboratory tests suggested a septic process. INVESTIGATIONS: The clinical and sonographic findings and computed tomography suggested an acute cholecystitis. TREATMENT AND COURSE: A cholecystectomy was performed. Microscopic examination revealed metastatic infiltration of the gall bladder by a medullary plasmocytoma. CONCLUSION: Secondary tumours of the gallbladder considered are thought to be rare. Since 1863 only 95 cases have been reported. The case discussed here is only the second one in which the metastatic tumor was a medullary plasmocytoma. But a search for published and confirmed cases indicates that secondary tumors of the gall bladder are not so rare. Metastatic tumors of the gall bladder should be kept in mind in the differential diagnosis of acute cholecystitis, especially in patients with an advanced primary tumor. PMID- 17357905 TI - [Hepatitis C infection with false negative serology in a patient with mixed cryoglobulinemic vasculitis]. AB - HISTORY AND ADMISSION FINDINGS: A 72-year-old man with nausea, fever and elevated inflammatory parameters was transferred for further diagnostic assessment and treatment. On examination a palpable purpura was obvious without any signs of infection. INVESTIGATIONS: Creatininekinase was 350 mmol/l with a proteinuria of 20 g per day. Histological examination revealed hypersensitivity vasculitis in the cutis and a membranoproliferative glomerulonephritis. In addition there was a mixed cryoglobulinemia with a negative test for hepatitis C virus. Further investigation revealed hepatitis C virus RNA genotype 1 b in the cryoprecipitate. DIAGNOSIS AND TREATMENT: The patient was successfully treated with with interferon alpha for 12 month. The nephrotic syndrome improved and the proteinuria ceased CONCLUSION: Mixed cryoglobulinemias are associated with hepatitis C virus infection in over 80% of cases. Normally it is easy to make the diagnosis serologically with an ELISA test. But in a few cases the virus RNA is only detectable in the cryoprecipitate. If there is a high suspicion of an hepatitis C infection with cryoglobulinemia but HCV serology is negative, it is essential that virus antigen and antibodies are searched for in the cryoprecipitate. PMID- 17357906 TI - [Ruptured Baker cyst with skin and muscle hematomas]. PMID- 17357907 TI - [Antibiotic therapy and prophylaxis in liver cirrhosis and infection]. PMID- 17357908 TI - [Long term effects of pulmonary rehabilitation in COPD and interstitial lung disease--synopsis of databases since 1990]. AB - The efficacy of pulmonary rehabilitation with a multi-disciplinary approach has been demonstrated especially in patients with chronic obstructive pulmonary disease (COPD). This review focuses particularly on the long-term outcome of pulmonary rehabilitation. Significant improvements have been demonstrated with respect to quality of life and exercise capacity up to one year after rehabilitation. Further investigations are still required on other outcome measures such as effects on repeated hospitalization, different types of rehabilitation (in-patient, out-patient, combined), and on rehabilitation of patients with non-obstructive pulmonary diseases. PMID- 17357910 TI - [beta2-Sympathomimetics: dangers in asthma therapy? Lessons from the SMART1 Study]. PMID- 17357914 TI - [Atrial fibrillation]. PMID- 17357950 TI - Treatment of biliary obstruction in selected patients by endoscopic ultrasonography (EUS)-guided transluminal biliary drainage. AB - BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) guided implantation of a biliary endoprosthesis or stent is the gold standard treatment for biliary obstructions. When the papilla cannot be traversed because there is pyloric or duodenal stenosis, or the catheter cannot be introduced, or because of previous gastrointestinal surgery (Billroth II gastric resection, Whipple procedure, gastrectomy with Roux-en-Y reconstruction), the alternative treatment is considered to be percutaneous transhepatic cholangiography and drainage (PTCD). The aim of the study was to investigate the further alternative of endoscopic ultrasound (EUS)-guided transgastric or transjejunal biliary drainage where PTCD failed or was declined, and particularly, the feasibility and outcome of this option. PATIENTS AND METHODS: Over 3 years all appropriate consecutive patients (as defined above) were enrolled in this prospective, observational, single-center, case series study, and patient and intervention data were recorded. Feasibility was characterized by success rate (regression of cholestasis), and outcomes by complication rate, mortality, and follow-up findings. RESULTS: Between November 2002 and December 2005, eight patients (in 10 interventions) underwent this new biliary drainage procedure. The routes were transesophageal (n = 1), transgastric (n = 4), and transjejunal (n = 3, including a rendezvous technique with ERCP [n = 1]). The indications were cholestasis, arising from recurrent tumor growth (n = 5, 62.5%), that included gastric carcinoma after previous gastrectomy (n = 4) and a periampullary carcinoma after previous Whipple procedure (n = 1); arising from Klatskin tumor (n = 2, 25%); and from benign stenosis of a hepaticojejunostomy (n = 1, 12.5%). Five patients (62.5%) received a metal stent, and three (37.5%) had a plastic prosthesis (8.5 Fr double-pigtail). The technical success rate was 90% (9/10) and the clinical success rate was 88.9% (8/9). There was only one case of cholangitis (12.5%) and slight postinterventional pain, but no severe complications such as bleeding or perforation, and no mortality. During follow-up (range 4 weeks to 3 years) re interventions were needed in two patients (20%) because of increasing cholestasis; these resulted in technical success and clinical improvement. CONCLUSION: EUS-guided transgastric or transjejunal biliary drainage is a reasonable, feasible and encouraging treatment option in selected patients as indicated, with a low peri-interventional risk. It broadens the therapeutic spectrum but still needs further evaluation and follow-up investigation. PMID- 17357951 TI - Covered self-expandable metal stents in pancreatic malignancy regardless of resectability: a new concept validated by a decision analysis. AB - BACKGROUND AND STUDY AIMS: The current treatment model for the management of malignant biliary obstruction is to place a plastic stent for unstaged pancreatic cancer. In patients with unresectable disease but a life expectancy of more than 6 months, self-expandable metal stents (SEMS) are favored because of their more prolonged patency. We analyzed the efficacy and cost-effectiveness of covered SEMS (CSEMS) in patients with pancreatic cancer and distal biliary obstruction without regard to surgical resectability. PATIENTS AND METHODS: Between March 2001 and March 2005, 101 consecutive patients with obstructive jaundice secondary to pancreatic cancer underwent placement of a CSEMS. Patients with resectable tumor were offered pancreaticoduodenectomy. A model was developed to compare the costs of CSEMS and polyethylene and DoubleLayer stents. RESULTS: A total of 21 patients underwent staging laparoscopy, of whom 16 had a resection (76%). The 85 patients who did not have a resection had a mean survival of 5.9 months (range 1 25 months) and a mean CSEMS patency duration of 5.5 months (range 1-16 months). Life-table analysis demonstrated CSEMS patency rates of 97% at 3 months, 85% at 6 months, and 68% at 12 months. In a cost model that accounted for polyethylene and DoubleLayer stent malfunction and surgical resections, initial CSEMS placement (3177 euros per patient) was a less costly intervention than either DoubleLayer stent placement (3224 euros per patient) or polyethylene stent placement with revision (3570 euros per patient). CONCLUSIONS: Covered SEMS are an effective treatment for distal biliary obstructions caused by pancreatic carcinoma. Their prolonged patency and removability makes them an attractive option for biliary decompression, regardless of resectability. The strategy of initial covered SEMS placement might be the most cost-effective strategy in these patients. PMID- 17357952 TI - Transgastric endoscopic ultrasonography-guided biliary drainage: results of a pilot study. AB - BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) access to the biliary tract is sometimes impossible and percutaneous access has the disadvantages of increased morbidity and patient discomfort. We present our first results with an alternative technique: endoscopic ultrasonography (EUS) guided transgastric biliary drainage. PATIENTS AND METHODS: 11 patients (7 men, mean age 64 years) were referred for failed ERCP and biliary obstruction (malignancy n = 8, benign conditions n = 3). The retrograde approach via the papilla had been impossible due to surgical anatomy, duodenal stenosis, and hilar stricture with occlusion of the left side. EUS-guided drainage was done with endoscopic and fluoroscopic monitoring. After puncture of the left biliary duct a guide wire was inserted into it followed by tract dilation using a cystostome. A plastic or a metallic stent was placed through this gastrobiliary fistula for bile drainage. RESULTS: EUS-guided left hepaticogastrostomy was successfully performed in 10/11 cases, with one failure of guide wire insertion after puncture. Plastic and covered metal stents were inserted in seven and three patients, respectively. Complications in the plastic stent group included one early occlusion requiring stent replacement, and one transient ileus. In the metallic stent group there was one bilioma and one cholangitis, due to stent shortening. Clinically, the stent was efficacious in all 10 cases; during a mean follow-up of 213 days (range 3-610), two patients presented with stent occlusion and one with stent migration, with successful endoscopic treatment in all. CONCLUSIONS: EUS-guided hepaticogastrostomy is an efficient technique and could be a future alternative to percutaneous biliary drainage or palliative surgical drainage. PMID- 17357953 TI - Efficacy of double-balloon enteroscopy in the evaluation and treatment of bleeding and non-bleeding small bowel disease. AB - Double-balloon enteroscopy (DBE) is a newly developed method allowing deep insertion of a thin endoscope into the small bowel, thereby enabling inspection, biopsy and endoscopic treatment of previously inaccessible lesions. This retrospective analysis evaluates the diagnostic and therapeutic efficacy in all patients undergoing DBE at our institution. A total of 109 DBEs were performed in 82 patients (57 patients with suspected small bowel blood loss and 25 patients with other indications). The diagnostic success rate was 51 of 82 (62 %) with a higher rate in bleeders in whom angiodysplasias were the most frequent diagnosis. DBE had therapeutic consequences in 47 patients (57 %), of whom 33 patients (40 %) underwent endoscopic therapy and 6 patients (7 %) surgery. In 4 patients, malignant neoplasias were newly diagnosed (2 gastrointestinal stroma tumors, 1 neuroendocrine tumor, 1 adenocarcinoma). Other diagnostic modalities were helpful in preselecting patients for DBE and choosing the more favorable (oral or anal) access. In 16 of 26 patients, pathological findings in videocapsule endoscopy were substantiated by DBE. In 7 patients, the findings of CT or MRI enteroclysis, and in 4 patients with hematochezia, the results of a preceding erythrocyte bleeding scan were confirmed by DBE. In conclusion, this series indicates that DBE of the small bowel - in concert with other diagnostic modalities - has a high diagnostic and therapeutic efficacy. PMID- 17357954 TI - [Recurrent gastrointestinal bleeding and aortic valve stenosis (Heyde syndrome): need for valve replacement?]. AB - Angiodysplasia are common in patients over the age of 60. Heyde syndrome describes the coincidence of aortic valve stenosis and gastrointestinal bleeding from angiodysplasia. We describe one characteristic case of aortic valve stenosis and gastrointestinal bleeding from angiodysplasia which subsided after replacement with an aortic valve bioprosthesis. We review the current literature and discuss the actual explanation approaches for this phenomenon. CONCLUSION: There seems to be a clear indication for valve replacement in the case of aortic valve-stenosis and gastrointestinal bleeding due to angiodysplasia. PMID- 17357955 TI - [Reflux-associated nutcracker oesophagus in a 49-year-old patient with non cardiac chest pain (NCCP)]. AB - A 49-year-old woman was admitted to our department because of intermittent left sided chest pain for the past 2 years. The patient reported an increasing frequency and duration of the symptoms which were independent from food intake, medication or physical exercises. A cardiac cause of the chest pain was excluded before admittance to our hospital. The initially performed upper endoscopy revealed a small oesophageal hiatal hernia but no signs of acute or chronic inflammation. Basal oesophageal manometry and pH monitoring confirmed the presence of a nutcracker oesophagus, defined by high-amplitude contractions of the distal oesophagus, in combination with a gastro-oesophageal reflux disease. The patient was treated with high-dose pantoprazole for 8 weeks before re examination. Interestingly, the symptoms completely disappeared upon medication and the relief of the chest pain was accompanied by normalisation of the nutcracker oesophagus pattern. Thus, our observation provides evidence for a causative role of acid reflux in the pathophysiology of the nutcracker oesophagus and, in addition, suggests that effective acid suppression might be a useful therapeutic tool to deal with this painful motility disorder of the oesophagus. PMID- 17357956 TI - [Topical mitomycin C treatment of a benign oesophageal stricture following caustic ingestion in a four-year-old boy]. AB - Accidental caustic ingestion is a common problem in young children at the age of 1 to 4 years. In cases of circular injuries of the oesophagus subsequent strictures can arise. Endoscopic balloon dilatation is the commonly used intervention but does not always lead to permanent improvement. We report the successful use of mitomycin C in a young boy in whom we could achieve ongoing relief of dysphagia after the unsuccessful long-term use of frequent endoscopic dilatations. PMID- 17357957 TI - [The Cochrane Library--a short introduction for gastroenterologists]. AB - The Cochrane Library is an important resource for evidence on the effectiveness of interventions in health care. The field of gastroenterology and hepatology is represented within the Cochrane Collaboration by four Cochrane review groups. The most prominent component of the library is the database of systematic reviews, produced by the Cochrane Collaboration. These offer valid information on relevant clinical topics based on comprehensive and skillful identification, evaluation and synthesis of clinical trials. Other components, library access and an introduction into searching the library are presented. PMID- 17357958 TI - [Vienna classification of Crohn's disease: helpful or dispensable? A critical view]. AB - A short review of phenotypic classification of Crohn's disease is given. Pitfalls in a clinical system of disease classification into different phenotypes and limitations of the Vienna classification of Crohn's disease are discussed. The concept of distinctive patterns of disease "behaviour" is criticized. The disease behaviour is not a persistent phenomenon and changes in the long-term follow-up significantly. Factors not addressed in the Vienna classification but, of course, influencing presentation and progression of Crohn's disease such as influences of early childhood, smoking and use of non-steroidal anti-inflammatory drugs are mentioned. The need of the classification criterion "age" is questioned. It is criticized that the Vienna classification has (at least until now) no consequences for the management of Crohn's disease. Experimental treatment approaches follow the current genetic or microbiological hypotheses and do not consider the Vienna classification system. In view of the philosophy of science the need of phenotypic classification into subgroups, clarification of mechanisms and experimentation with drug treatments in the elaboration of disease causation is stressed. In recent years much progress has been made in clarifying Kirsner's "mysterious and multiplex" nature of inflammatory bowel disease. However, as physicians we have to focus on the "menace" of a chronic disease for the patient's life and not only to treat the hole of the patient with "biologicals" but rather to treat the whole patient in a bio-psycho-social approach. PMID- 17357959 TI - [Digestive and predigestive functions in patients with eating disorders]. AB - Patients with eating disorders (anorexia nervosa, AN; bulimia nervosa, BN) frequently exhibit gastrointestinal symptoms and altered gastrointestinal functions, especially delayed gastric emptying. These symptoms are regarded as secondary to the disordered eating behaviour, vomiting or laxative misuse. They often improve during successful therapy. There are, however, studies showing that in addition predigestive functions (smell, taste, cephalic phase of digestion) and the hormonal regulation of digestion may be changed in eating disorders. This underlines the possibility that, in a subpopulation of patients with AN and BN, the disturbed digestive and predigestive functions may be involved in the pathogenesis of the eating disorders. The current literature is analysed and summarised in this context. PMID- 17357961 TI - Exercise testing in children and adolescents with chronic fatigue syndrome. AB - The objective of this study was to evaluate exercise capacity in children and adolescents diagnosed with Chronic Fatigue Syndrome (CFS). We examined 20 patients (12 girls and 8 boys; mean age 14.9 +/- 3.7 years) diagnosed with CFS. Exercise capacity was measured using a maximal exercise test on a bicycle ergometer and an expired gas analysis system. Fatigue was assessed using a questionnaire and a daily activity diary was used to describe activities for three days. Z-scores were calculated using age- and sex-matched reference values. Z-scores in children and adolescents with CFS were - 0.33 +/- 1.0 (p = 0.17) for peak oxygen uptake, - 1.13 +/- 1.41 (p = 0.002) for relative peak oxygen uptake [ml/kg/min] and - 0.93 +/- 1.29 (p = 0.07) for maximal work load. Both heart rate and blood pressure at peak performance were significantly reduced compared to reference values. Fatigue levels were significantly positively associated with age and negatively with blood pressure at peak exercise (p < 0.05). In conclusion maximum exercise testing was feasible in young people with CFS. Maximal exercise capacity was only reduced in a minority of the patients and was related to current physical activity levels. PMID- 17357962 TI - .VO2 kinetics during supramaximal exercise: relationship with oxygen deficit and 800-m running performance. AB - The aim of this study was to compare .VO2 kinetics of highly- versus recreationally-trained subjects during a constant velocity test of supramaximal intensity. Eighteen trained male subjects were recruited to one of two groups: highly trained (HT, n = 8, .VO(2max) = 70.1 +/- 6.5 ml . min (-1) . kg (-1)) and recreationally trained (RT, n = 10, .VO(2max) = 63.2 +/- 6.4 ml . min (-1) . kg ( 1)). All subjects performed an incremental test to exhaustion for the determination of .VO(2max) and peak treadmill velocity (PTV), two constant velocity tests at 110 % of PTV to determine .VO2 kinetics and oxygen deficit (O(2)def), and a 800-m time trial to determine running performance (mean velocity over the distance, V (800 m)). We found significant differences between HT and RT for the on-transient of the .VO2 response (tau, 24.7 +/- 3.3 and 30.9 +/- 7.0 s, respectively), the amplitude of the .VO2 response (60.0 +/- 5.0 and 53.5 +/- 5.7 ml . min (-1) . kg (-1), respectively) and V (800 m) (6.27 +/- 2.1 and 5.45 +/- 0.38 m . s (-1), respectively). O(2)def (24.6 +/- 2.7 and 27.7 +/- 7.8 ml . kg ( 1), respectively) and the gain of the .VO2 response (193 +/- 14 and 194 +/- 13 ml . kg (-1) . m (-1), respectively) were similar between groups. tau was associated with O(2)def (r = 0.90, p < 0.05), but not with V (800 m) (r = 0.30, p > 0.05). It was concluded that HT subjects exhibited faster on-kinetics and higher amplitude than their RT counterparts. The higher amplitude was not thought to reflect any difference in underlying physiological mechanisms. The faster tau, whose exact mechanisms remain to be elucidated, may have practical implications for coaches. PMID- 17357963 TI - Relationship between strength level and pedal rate. AB - The purpose of this study was to examine the relationship between strength capacity and preferred and optimal cadence in well trained cyclists. Eighteen cyclists participated in this study. Each subject completed three sessions. The initial session was to evaluate the maximal isokinetic voluntary contraction level of lower limb. The second session was an incremental test to exhaustion. During the third session subjects performed a constant cycling exercise (20 min) conducted at five randomly cadences (50, 70, 90, 110 rpm) and at the preferred cadence (FCC) at the power reached at ventilatory threshold. Cardiorespiratory and EMG values were recorded. A metabolic optimum (EOC) was observed at 63.5 +/- 7.8 rpm different from preferred cadence (FCC, 90.6 +/- 9.1 rpm). No difference was found between FCC and the neuromuscular optimal cadence (NOC, 93.5 +/- 4). Significant relationships were found between EOC, NOC and strength capacities (r = - 0.75 and - 0. 63), whereas FCC was only related with VO2max (r = 0.59). The main finding of this study was that during submaximal cycling energetically optimal cadence or neuromuscular optimum in trained cyclists was significantly related with strength capacity and whereas preferred cadence seems to be related with endurance training status of cyclists. PMID- 17357964 TI - NRF2 genotype improves endurance capacity in response to training. AB - The aim of this work was to examine the association between the polymorphisms in nuclear respiratory factor (NRF2) gene and endurance capacity measured prior to and after an 18-wk endurance training program in young Chinese men. The phenotypes measured were running economy (RE) and VO(2max). The RE was determined by measuring submaximal VO(2) for 5 min at a constant running speed of 12 km x h (-1) and VO(2max) was measured during an incremental test to volitional exhaustion. Genomic DNA was extracted from white cells of peripheral blood and the genotypes were examined in SNPrs12594956, rs8031031 and rs7181866 by PCR RFLP. Genotype distributions were in Hardy-Weinberg equilibrium at three loci, and linkage disequilibrium was observed (LD D' = 1 and r (2) = 0.903) between rs8031031 and rs7181866. The VO(2max) was associated with rs12594956 at baseline while the training response of VO(2) at RE, was associated with rs12594956, rs8031031 and rs7181866. When the three SNPs were considered together, those carrying the ATG haplotype had 57.5 % higher training response in VO(2) at RE (p = 0.006) than non-carriers. In conclusion, polymorphisms in NRF2 gene may explain some of the between-person variance in endurance capacity. PMID- 17357965 TI - Intermittent hypoxia does not increase exercise ventilation at simulated moderate altitude. AB - Recent human studies have shown that resting hypoxic ventilatory response (HVR), which is an index of ventilatory chemosensitivity to hypoxia, increased after short-term intermittent hypoxia at rest. In addition, intermittent hypoxia leads to increases in ventilation and arterial oxygen saturation (SaO (2)) during exercise at simulated high altitude, with the increase in ventilation correlated to the change in HVR. However, no study has been made to clarify the relationship between ventilatory chemosensitivity and the exercise ventilation at moderate altitude following intermittent hypoxia during a resting state. The purpose of the present study, therefore, was to elucidate whether intermittent hypoxia at rest induces the increase in ventilation during exercise at moderate altitude that is accompanied by an increase in hypoxic chemosensitivity. Eighteen trained male runners were assigned to three groups, i.e., the first hypoxic group (H-1 group, n = 6), the second hypoxic group (H-2 group, n = 6), and a control group (C group, n = 6). The hypoxic tent system was utilized for intermittent hypoxia, and the oxygen levels in the tent were maintained at 15.5 +/- 0.1 % (simulated 2500 m altitude) for the H-1 group and 12.3 +/- 0.2 % (simulated 4300 m altitude) for the H-2 group. The H-1 and H-2 groups spent 1 hour per day in the hypoxic tent for 1 week. Maximal and submaximal exercise tests while breathing 15.5 +/- 0.01 % O (2) (simulated altitude of 2500 m) were performed before and after intermittent hypoxia. Resting HVR was also determined in each subject using a progressive isocapnic hypoxic method. In the H-2 group, HVR increased significantly (p < 0.05) following intermittent hypoxia, while no change in HVR was found in the H-1 or C group. Neither ventilation nor SaO (2) during maximal and submaximal exercise at a simulated altitude of 2500 m were changed in either group after 1 hour per day for 1 week of intermittent hypoxia. These results suggest that the change in resting hypoxic chemosensitivity after short-term intermittent hypoxia does not affect ventilation during exercise at moderate altitude. PMID- 17357966 TI - Racial differences in tendon rupture incidence. AB - Despite some anecdotal evidence, the racial differences in tendon injuries have received little attention in the literature. We sought to determine the effect of race on major tendon injuries. A search was performed according to the International Classification of Diseases, Ninth Revision, Clinical Modification code 727.65 (rupture of quadriceps tendon), 727.66 (rupture of patellar tendon), and 727.67 (rupture of Achilles tendon) using the U. S. Defense Medical Epidemiology Database (DMED). Multivariate poisson regression was used to estimate the rate of major tendon rupture per 1000 person-years, while controlling for differences in gender, service, rank, and age for each code. We computed rate ratios and 95% confidence intervals using whites as the referent category. The adjusted rate ratio for black service members when compared to white service members was 2.89 (95% CI 2.42, 3.44) for quadriceps tendon tears, 4.52 (95% CI 3.94, 5.19) for patellar tendon tears, and 3.58 (95% CI 3.31, 3.88) for Achilles tendon tears. There appears to be a significant relative predisposition toward lower-extremity major tendon rupture in black U. S. service members when compared to white service members. Investigation of the racial differences in risk factors is warranted. PMID- 17357967 TI - Muscle strength evaluations after ACL reconstruction. AB - The quadriceps and hamstring muscle strengths of 16 patients operated using a bone-patellar tendon-bone (BTB) autograft and 32 patients operated using a quadruple hamstring autograft for an arthroscopic anterior cruciate ligament (ACL) reconstruction were analyzed 4- to 7-years postoperatively. Standardized isokinetic testing, a clinical evaluation and instrumented assessment of knee laxity were done. The findings showed no significant strength deficits between the patients in the BTB and Hamstring groups and the deficits were, in general, small. The quadriceps and hamstring muscle strengths were better in patients with a longer than shorter follow-up and stable knees had less knee flexion torque deficit than unstable knees. Strength deficit was associated with lower Lysholm knee scores. The findings of this study showed that the muscle strengths of the operated limb had a positive association with the functional outcome of the knee in the long-term and support the use of active rehabilitation after ACL reconstruction. PMID- 17357968 TI - Effect of exercise intensity on exercise-induced lymphocyte apoptosis. AB - Because lymphocyte apoptosis is significantly elevated immediately following high intensity exercise in humans, it seems intuitive that the cell death process must be initiated at some point during the task. This study was designed to determine whether exercise-induced lymphocyte apoptosis occurs at a threshold level of intensity, or exists only following maximal or near-maximal exercise intensities. Fourteen untrained subjects completed a discontinuous, incremental treadmill test to exhaustion (.VO(2max)). Blood for films was sampled before the test, immediately after each work stage, and for 1-h postexercise. Blood smears were stained with May-Grunwald Giemsa and lymphocytes were evaluated for characteristic features of apoptosis. The apoptotic index (AI) during exercise at 38 % .VO(2max) was similar to pre-exercise but significantly elevated at an intensity approximating 61 % .VO(2max) (p < 0.0001). Significant increases in apoptosis were noted with additional elevations in exercise intensity (i.e., 76 %, 89 %, and 100 %, p < 0.0001). Following 20 min of recovery, AI was significantly lower than values obtained immediately postexercise (p < 0.0001). Forty minutes of recovery resulted in a further significant decrease (p < 0.0001), and by 1-h postexercise, AI was similar to pre-exercise values. Results indicate that the exercise intensity threshold for inducing an increase in lymphocyte apoptosis occurs between 40 and 60 % .VO(2max). In addition, since values return to baseline within 1 h following exhaustive exercise, it is unlikely that factors responsible for the apoptotic response in lymphocytes maintain a prolonged presence once exercise has been terminated. PMID- 17357969 TI - Risk factor profile for sudden cardiac death during mountain hiking. AB - Mountain hiking is associated with a death rate of about 4 deaths per 100,000 hikers annually. About 50 % of all fatalities during mountain hiking are sudden cardiac deaths (SCDs). But there are only few data available regarding risk factors and triggers associated with SCD during mountain hiking. Thus, a case control analysis between persons who died suddenly during mountain hiking and randomly selected controls was carried out. Risk factor profiles of 179 males over the age of 34 who suffered SCD during mountain hiking were compared to those of 537 matched controls. Hikers who died suddenly during mountain hiking were much more likely to have had a prior MI (17% vs. 0.9%; p < 0.001), known coronary artery disease (CAD) without prior MI (17 % vs. 4%; p < 0.001), diabetes (6% vs. 1 %; p < 0.001), hypercholesterolemia (54 % vs. 20%; p < 0.001), and were less engaged in regular mountain sports activities (31% vs. 58%; p < 0.001) compared to hikers from the control group. Based on the reported relationship between traditional risk factors and coronary plaque morphology, acute plaque rupture with thrombus formation and subsequent lethal arrhythmias may be assumed to be a dominant mechanism precipitating SCD during hiking. In contrast, in skiers especially non-occlusive plaques may precipitate ischemia leading to an imbalance between oxygen demand and supply and subsequent lethal arrhythmias. As preventive measures recommended to hikers at risk, adaptation to regular mountain sports activities by an adequate training program and pharmacological interventions, e.g. lipid lowering drugs, aspirin, and beta-blockers, should be considered. PMID- 17357970 TI - Identification and properties of 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy) trans-stilbene from Morus bombycis Koidzumi roots. AB - 2,5-Dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene was identified from Morus bombycis Koidzumi roots. The 2,5-dihydroxy-4,3'-di(beta-D glucopyranosyloxy)-trans-stilbene at a dose of 400-600 mg/kg had hepatoprotective activity comparable to the standard agent, silymarin. The biochemical assays were confirmed by histological observations showing that the 2,5-dihydroxy-4,3' di(beta-d-glucopyranosyloxy)-trans-stilbene from Morus bombycis Koidzumi roots decreased cell ballooning in response to CCl4 treatment. These results demonstrate that the 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans stilbene component has a liver protective action against CCl4-induced hepatotoxicity. PMID- 17357971 TI - Pycnogenol reduces talc-induced neoplastic transformation in human ovarian cell cultures. AB - Talc and poor diet have been suggested to increase the risk of developing ovarian cancer; which can be reduced by a diet rich in fruit and vegetables. Talc is ubiquitous despite concern about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. It was recently shown that Pycnogenol (Pyc; a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine bark) was selectively toxic to established malignant ovarian germ cells. This study investigated talc-induced carcinogenesis and Pyc induced chemoprevention. Normal human epithelial and granulosa ovarian cell lines and polymorphonuclear neutrophils (PMN) were treated with talc, or pretreated with Pyc then talc. Cell viability, reactive oxygen species (ROS) generation and neoplastic transformation by soft agar assay were measured. Talc increased proliferation, induced neoplastic transformation and increased ROS generation time-dependently in the ovarian cells and dose-dependently in the PMN. Pretreatment with Pyc inhibited the talc-induced increase in proliferation, decreased the number of transformed colonies and decreased the ROS generation in the ovarian cells. The data suggest that talc may contribute to ovarian neoplastic transformation and Pyc reduced the talc-induced transformation. Taken together, Pyc may prove to be a potent chemopreventative agent against ovarian carcinogenesis. PMID- 17357972 TI - Antiviral triterpenoids from the medicinal plant Schefflera heptaphylla. AB - Schefflera heptaphylla (L.) Frodin is a principal ingredient of an herbal tea formulation widely used for the treatment of common cold in southern China. An extract of the long leafstalk of the compound leaf of S. heptaphylla exhibited the most potent antiviral activity against respiratory syncytial virus (RSV). Further antiviral-guided fractionation and isolation of the leafstalk extract of S. heptaphylla led to obtain two highly active pure triterpenoids, namely 3alpha hydroxylup-20(29)-ene-23,28-dioic acid and 3-epi-betulinic acid 3-O-sulfate, together with an inactive saponin, 3alpha-hydroxylup-20(29)-ene-23,28-dioic acid 28-O-alpha-l-rhamnopyranosyl-(1-->4)-O-beta-d-glucopyranosyl-(1-->6)-beta-d glucopyranoside. An antiviral assay using a cytopathic effect (CPE) reduction method showed that the two triterpenoids possessed broader antiviral activity against respiratory syncytial virus (RSV) with a similar 50% inhibition concentration (IC(50)) value of 6.25 microg/mL, influenza A (H1N1) virus with IC(50) values of 25 and 31.3 microg/mL, Coxsackie B3 (Cox B3) virus with IC(50) values of 12.5 and 20 microg/mL and herpes simplex virus type 1 (HSV-1) with IC(50) values of 18.8 and 25 microg/mL, respectively, whereas the saponin did not have antiviral activity against these four viruses at a concentration of 100 microg/mL. PMID- 17357973 TI - Studies on synthesis and anion recognition properties of (3'-nitrobenzo)[2,3-d] (3''-nitrobenzo)[9,10-d]-1,4,8,11-tetraazacyclotetradecane-5,7,12,14-tetraone. AB - A novel artificial receptor, (3'-nitrobenzo)[2,3-d]-(3''-nitrobenzo)[9,10-d] 1,4,8,11-tetraazacyclotetradecane-5,7,12,14-tetraone, was designed and synthesized. The interactions of this receptor with different anions were determined by UV-vis and (1)H NMR titration experiments, and their affinity constants to different anions were compared with those of other similar/different systems. The results indicated that this receptor showed a high selective and recognitive ability for F(-) among F(-), Cl(-), Br(-), I(-), AcO(-), OH(-), and H(2)PO(4)(-). Moreover, the low energy configuration of this receptor was further determined by means of theoretical investigations. PMID- 17357974 TI - In vitro cytotoxicity of some medicinal plants from Georgian Amaryllidaceae. AB - Using an ethnomedical data approach, some Georgian plants, which are used in Georgian traditional medicine for cancer or non-cancer diseases, were collected and evaluated for cytotoxic activity. The cytotoxic effect of the methanol extracts of species from the genera Galanthus and Leucojum was evaluated in vitro on three human cell lines (Hela, ephitheloid cervix carcinoma; HCT-116, colon carcinoma; HL-60, acute myeloid leukaemia). Cell type cytotoxic specificity was observed for some extracts. Overall, the HCT-116 cells were much more sensitive to most of the extracts than were the other cell lines. Plants that showed pronounced cytotoxic activity will be further evaluated for the possible isolation of active antitumour compounds. PMID- 17357975 TI - Screening seeds of some Scottish plants for free radical scavenging activity. AB - From a consideration of ethnobotanical and taxonomic information, seeds of 45 Scottish plant species encompassing 23 different families were obtained from authentic seed suppliers. The n-hexane, dichloromethane (DCM) and methanol (MeOH) extracts were assessed, both qualitatively and quantitatively, for free radical scavenging activity in the DPPH assay. The MeOH extracts of 37 species exhibited low to high levels of free radical scavenging activity (RC50 values ranging from 2.00 to 4.7 x 10(-4) mg/mL), and Alliaria petiolata, Prunus padus and Prunus spinosa were the most potent antioxidant extracts. The DCM extracts of 17 species showed similar levels of activity, and among those, Prunus padus and Prunus spinosa extracts were the most active with RC50 values of 2.5 x 10(-4) and 5.0 x 10(-4) mg/mL, respectively. The n-hexane extracts were much less active than the MeOH and DCM extracts, and 17 species, with the exception of Glechoma hederacea (RC50 = 1.94 x 10(-4)) displayed low to moderate levels of free radical scavenging property (RC50 values ranging from 2.00 to 8.7 x 10(-3) mg/mL). PMID- 17357976 TI - Effect of a diterpenoid from Salvia cinnabarina on arterial blood pressure in rats. AB - The effect of a diterpenoid isolated from Salvia cinnabarina, 3,4-seicosopimar 4(18),7,15-triene-3-oic acid (SCB), on arterial blood pressure was evaluated in anaesthetized rats. Male Wistar rats, anaesthetized with urethane (sol. 10% p/v; 10 mL/kg), underwent surgery for continuous monitoring of arterial blood pressure. After preliminary experiments to evaluate the dose response (3, 10 and 30 mg/kg i.v.) of SCB, a dose of 3 mg/kg was chosen for all successive experiments. On different groups of rats treated with the ganglion-blocking agent chlorisondamine (2.5 mg/kg i.p.) the effect of SCB (3 mg/kg i.v.) was evaluated before and following an infusion of the nitric oxide synthase inhibitor L-NAME (0.3 mg/kg/min i.v.). Intravenous administration of SCB at doses of 3, 10 and 30 mg/kg led to a fall in mean arterial blood pressure (MABP) of 14.75 +/- 1.44 mmHg, 36.60 +/- 31.40 mmHg and 31.40 +/- 6.28 mmHg, respectively (n = 4-5), that was not modified by treatment of the rat with chlorisondamine nor with L-NAME. The results demonstrate a hypotensive effect of SCB - due to a peripheral mechanism but independent of endothelial nitric oxide release. PMID- 17357977 TI - Preventative antiinflammatory effect of potamogetonan, a pectin from the common pondweed Potamogeton natans L. AB - The pectic polysaccharide named potamogetonan (PN) was obtained using extraction of the leaves and stems of the common pondweed Potamogeton natans L. by an aqueous ammonium oxalate. The purified potamogetonan PN-300 was obtained using membrane ultrafiltration of PN and proved to be pectin with a molecular weight of 300 kDa. The capacity of potamogetonan PN-300 to prevent inflammation was assessed using a carrageenan paw edema test in mice. Oral administration of PN 300 24 h prior to induction of inflammation was found to reduce edema formation in a dose-related manner. The maximal effect of PN-300 was observed at 1 h after carrageenan injection (60% reduction of footpad swelling) and was comparable to that of indomethacin. The delayed edema (5 h) was less affected by pre administration of PN-300 (33% reduction). PN-300 was found to improve the survival of mice subjected to a lethal dose of LPS. The anti-endotoxemic effect of PN-300 was shown to be mediated by decreased TNF-alpha and IL-1beta and increased IL-10 production.Thus, a pectin named potamogetonan PN-300 was isolated from P. natans and was shown to possess a preventive antiinflammatory effect following oral administration. PMID- 17357978 TI - Inhibition of polyphenoloxidase activity by mixtures of heated cysteine derivatives with carbonyl compounds. AB - It had previously been shown that soluble Maillard reaction products (MRP) made from thiol compounds and glucose or fructose contained powerful inhibitors of various fruit and vegetable polyphenoloxidase (PPO) activity. In MRP from cysteine and glucose, the amount of hydroxymethylfurfural (HMF) formed increased with the increase in glucose concentration (0-1 M), particularly under acidic (pH 2) conditions. Using model mixtures containing a preheated cysteine-derived compound and a carbonyl component, especially HMF, furfural and benzaldehyde, we showed that the neoformed compounds produced exhibited a stronger inhibitory potency toward PPO activity of eggplant, apple, and mushroom than former MRP. Optimal reaction conditions for the formation of inhibitory compounds when HMF reacted with preheated cysteine were investigated. It was found that a reactants molar ratio of 1:1 and a reaction time exceeding 1 h were the most efficient reaction conditions to generate inhibitory compounds. The stability of the newly formed products, evaluated during storage, showed that their inhibitory potency was globally kept at 4, 21, and 37 degrees C for 72 h but was unstable when stored at -20 degrees C and lost when exposed to UV radiations for 24 h. PMID- 17357979 TI - Lung level of HMBG1 is elevated in response to advanced glycation end product enriched food in vivo. AB - High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein that can be actively released from the cell in certain conditions thereby mediating cytokine-like function. While nuclear HMGB1 modulates the transcriptional activity of cells, extracellular HMGB1 partially acts via binding to the receptor for advanced glycation end products (RAGE), which is highly expressed in lung tissue. Therefore, we studied the impact of food-derived advanced glycation end products (AGEs), the Maillard reaction products, on the lung expression of HMGB1. Feeding rats with AGE-rich diet, containing either bread crust or coffee beverage, resulted in an upregulation of HMGB1 mRNA and protein especially in those animals receiving bread crust diet. The expression of RAGE was not influenced. Moreover, we revealed a positive correlation between an increased lung AGE level and HMGB1 protein expression in both animal groups receiving either bread crust or coffee extract but not in the control group. In contrast, the ageing-related AGE accumulation was not associated with an increased level of HMGB1 protein in lung tissue from senescent (100 wk) compared to young-adult (24 wk) rats. Our data suggest a physiological role of food- but not ageing associated AGEs in the regulation of the HMGB1 expression in lung. PMID- 17357980 TI - Parameters for the evaluation of the thermal damage and nutraceutical potential of lupin-based ingredients and food products. AB - Foods based on sweet lupin proteins are gaining attention from industry and consumers because of their possible role in the prevention of cardiovascular disease. When promoting lupin-based foods for inclusion in a daily diet, the thermal damage suffered during processing is of relevance to the bioactive and nutritional quality of the food product. N-(2-furoylmethyl)-L-lysine (furosine) quantification demonstrates that currently available sweet lupin protein isolates have a thermal damage comparable to or lower than other traditional food ingredients, and are a good source of lysine in non-dairy products. In lupin based foods claiming to have cholesterol-lowering potential, shotgun proteomics offers itself as a fast and effective screening method for assessing the biological availability of active peptides. Such a method is readily applicable to other legume-enriched food products. PMID- 17357981 TI - Formation of 5-hydroxymethyl-2-furfural (HMF) and 5-hydroxymethyl-2-furoic acid during roasting of coffee. AB - The formation of 5-hydroxymethyl-2-furfural (HMF) and 5-hydroxymethyl-2-furoic acid (HMFA) during roasting of coffee was studied. At 240 degrees C the maximum concentration of HMF occurs after 3 min with a quick degradation up to 10 min when most of the HMF has disappeared again. Similar to 5-hydroxymethyl-furfural, HMFA is formed in coffee but not in a model system consisting of sucrose, alanine with or without chlorogenic acid. It was shown that HMFA is produced from different precursors than HMF namely glyceraldehyde and pyruvate. The comparison of the laboratory scale roasting with industrial roasting showed that 5 hydroxymethyl-furfural decreases with a higher degree of roasting whereas HMFA did not change. In the laboratory scale experiments, the highest concentration of 5-hydroxymethyl-furfural in coffee (909 microg/g) was obtained after 3 min and the maximum concentration of HMFA after 4 min (150 microg/g). Industrially roasted coffee contained up to 350 microg/g 5-hydroxymethyl-furfural and 140 microg/g HMFA. PMID- 17357982 TI - Off-line liquid chromatography-MALDI by with various matrices and tandem mass spectrometry for analysis of glycated human serum albumin tryptic peptides. AB - Advanced glycation end-product (AGE)/peptides, arising from in vivo digestion of glycated proteins, are biologically important compounds, due to their reactivity against circulating and tissue proteins. For information on their possible structure, in vitro glycation of HSA and its further enzymatic digestion were performed. The resulting digestion product mixture was analysed directly by MALDI MS with various matrices [2,5-dihydroxy benzoic acid (DHB) and alpha-cyano-4 hydroxy cinnamic acid (CHCA)]. Alternatively, offline microbore LC prior to MALDI analysis was used, and showed that 63% of the free amino groups prone to glycation are modified, indicating the contemporary presence of unglycated peptides. This result proves that, regardless of the high glucose concentration employed for HSA incubation, glycation does not go to completion. Further studies showed that the collisionally activated decomposition of singly charged glycated peptides leads to specific fragmentation pathways, all related to the condensed glucose molecule. These unique product ions can be used as effective markers to establish the presence of a glucose molecule within a peptide ion. PMID- 17357983 TI - Influence of model melanoidins on calcium-dependent transport mechanisms in smooth muscle tissue. AB - Melanoidins obtained from L-arginine and D-glucose (MW > 3500 Da) were tested for their ability to influence the contractility of gastric smooth muscles. A study within the range 0.1-10 mg/mL revealed that at low concentrations, the melanoidins provoked concentration-dependent contraction, whereas a muscle relaxation was registered at high concentrations. The contraction was preceded by changes in the calcium membrane current as measured by single sucrose-gap method and significantly attenuated by the calcium channel blockers D-600 and nifedipine. Measurements with Ca(2+)-selective electrode showed that the melanoidins decreased the concentration of ionized Ca(2+ )in tissue bath in concentration-dependent manner. Experiments carried out in solutions with lower than normal Ca(2+) concentration and using melanoidins preliminary saturated with Ca(2+ )confirmed that the calcium chelation by melanoidins was a key contributing cause for the development of relaxant response. The results obtained showed that the melanoidins could influence the contractility of smooth muscles through at least two pathways: at low concentrations they caused depolarization and activation of L-type calcium channels, stimulated the Ca(2+ )influx, and provoked contraction, whereas at high concentrations calcium binding by melanoidins led to significant depletion of extracellular calcium ions and contributed to the relaxation process observed. PMID- 17357984 TI - Proteolysis of milk proteins lactosylated in model systems. AB - Five different milk proteins (alpha-casein, beta-casein, kappa-casein, beta lactoglobulin, and lactoferrin) and a peptide substrate were applied as substrates for the investigation of how lactosylation affected proteolysis by different proteases. After a lactosylation period of 4 days in aqueous solution, at 65 degrees C and pH 6.8 in a protein: lactose ratio of 1000 the proteins were enzymatically hydrolyzed by the three milk relevant proteases plasmin, cathepsin D, and chymosin. Lactosylation of all substrates affected hydrolysis by plasmin negatively, with the largest effect on the globular proteins. This could be explained by modification of lysine residues, being the preferred cleavage site for plasmin, but also the residue generally preferred for lactosylation. Lactosylation of the caseins and of beta-lactoglobulin did not affect subsequent cleavage by cathepsin D and chymosin significantly, but for beta-lactoglobulin, both the secondary as well as the tertiary structure were affected by lactosylation. In contrast, decreased hydrolysis by cathepsin D and chymosin was observed for lactoferrin after lactosylation. Decreased hydrolysis may be caused by a more compact tertiary structure induced by lactosylation of lactoferrin, as indicated by fluorescence spectroscopy measurements. PMID- 17357985 TI - Modeling of acrylamide formation and browning ratio in potato chips by artificial neural network. AB - The artificial neural network (ANN) modeling approach was used to predict acrylamide formation and browning ratio (%) in potato chips as influenced by time x temperature covariants. A series of feed-forward type network models with back propagation training algorithm were developed. Among various network configurations, 4-5-3-2 configuration was found as the best performing network topology. Four neurons in the input layer were reflecting the asparagine concentration, glucose concentration, frying temperature, and frying time. The output layer had two neurons representing acrylamide concentration and browning ratio of potato chips. The ANN modeling approach was shown to successfully predict acrylamide concentration (R = 0.992) and browning ratio (R = 0.997) of potato chips during frying at different temperatures in time-dependent manner for potatoes having different concentrations of asparagine and glucose. It was concluded that ANN modeling is a useful predictive tool which considers only the input and output variables rather than the complex chemistry. PMID- 17357986 TI - Vinylogous Amadori rearrangement: implications in food and biological systems. AB - The 4-hydroxy-alkenals are important lipid peroxidation products and are known to play a major role both in the development of degenerative diseases in biological systems and off-flavors, or rancidity in food systems. The 4-hydroxy-alkenals can also be formed in nonlipid systems from 2-deoxy-sugar moieties such as 2-deoxy ribose. FTIR spectroscopic evidence was provided for such a transformation catalyzed by amino acids through monitoring the decrease in intensity of the aldehydic band centered at 1716 cm(-1) of the open form of 2-deoxy-ribose and increase in the intensity of the formed conjugated aldehydic band centered at 1672 cm(-1). Furthermore, 4-hydroxy-alkenals can react with nitrogen nucleophiles such as amino acids and proteins to form Schiff base adducts that are able to undergo vinylogous Amadori rearrangement (vARP) and subsequently cyclize to generate a pyrrole moiety. This cyclization is prevented in the case of secondary amino acids such as proline to form a stable vinylogous Amadori rearrangement product (vARP). Monitoring this reaction of proline with 4-hydroxy-2-nonenal (HNE) has indicated that within 15 min at 28 degrees C the 1685 cm(-1) band of HNE completely disappears and that at 50 degrees C, vARP is formed within 5 min, as indicated by the formation of a characteristic band at 1709 cm(-1). PMID- 17357987 TI - Maillard reaction products enriched food extract reduce the expression of myofibroblast phenotype markers. AB - Advanced glycation end products (AGE) are associated with a wide range of degenerative diseases. The present investigation aimed at analysing the influence of AGE containing nutritional extracts on cardiac fibroblasts (CFs) as the major cell type responsible for cardiac fibrosis. Mice CFs were treated with bread crust extract (BCE) which contained significant amounts of a variety of AGE modifications. BCE treatment with up to 30 mg/mL did not impair cell viability. Furthermore, BCE induced a moderate elevation of reactive oxygen species (ROS) production and activation of redox sensitive pathways like the p42/44(MAPK), p38(MAPK) and NF-kappaB but did not alter Akt kinase phosphorylation. Expression of smooth muscle alpha-actin and tropomyosin-1, which represent markers for myofibroblast differentiation, was reduced after bread crust treatment. These data suggest a putative antifibrotic effect of melanoidin-rich food. PMID- 17357988 TI - Wilcoxon-based group sequential designs for comparison of areas under two correlated ROC curves. AB - Clinical studies to evaluate the relative accuracies of two diagnostic modalities via their receiver operating characteristic (ROC) curves are currently conducted using fixed sample designs: cases are accrued until a predetermined sample size is achieved and, at that point, the areas under the ROC curves are computed and compared (Radiology 1982; 143:29-36; Radiology 1983; 148:839-843). In prospective ROC studies (Radiology 1990; 175:571-575), participants are recruited from a clinically defined cohort and diagnostic test information is obtained and interpreted in advance of ascertaining the definitive proof of diagnosis ('gold standard'). In retrospective studies, cases are selected from a set of patient records and their diagnostic tests are interpreted without knowledge of the 'gold standard'. The conduct of ROC studies requires considerable effort and resources, particularly for the collection of 'gold standard' information. Thus, it is highly desirable to search for designs which are more efficient than using a fixed sample. In this paper, we discuss the formulation and application of group sequential designs (GSDs) to comparative ROC studies based on non-parametric Wilcoxon estimators of the area under the ROC curves. The approach is applicable to comparisons of ROC curve areas of two tests measured on either continuous or ordinal scales on same cases ('paired' designs) with one reader. The adoption of GSDs may lead to substantial savings in the number of required cases, thus resulting in both time and resource use efficiency. PMID- 17357989 TI - Regression B-spline smoothing in Bayesian disease mapping: with an application to patient safety surveillance. AB - In the context of Bayesian disease mapping, recent literature presents generalized linear mixed models that engender spatial smoothing. The methods assume spatially varying random effects as a route to partially pooling data and 'borrowing strength' in small-area estimation. When spatiotemporal disease rates are available for sequential risk mapping of several time periods, the 'smoothing' issue may be explored by considering spatial smoothing, temporal smoothing and spatiotemporal interaction. In this paper, these considerations are motivated and explored through development of a Bayesian semiparametric disease mapping model framework which facilitates temporal smoothing of rates and relative risks via regression B-splines with mixed-effect representation of coefficients. Specifically, we develop spatial priors such as multivariate Gaussian Markov random fields and non-spatial priors such as unstructured multivariate Gaussian distributions and illustrate how time trends in small-area relative risks may be explored by splines which vary in either a spatially structured or unstructured manner. In particular, we show that with suitable prior specifications for the random effects ensemble, small-area relative risk trends may be fit by 'spatially varying' or randomly varying B-splines. A recently developed Bayesian hierarchical model selection criterion, the deviance information criterion, is used to assess the trade-off between goodness-of-fit and smoothness and to select the number of knots. The methodological development aims to provide reliable information about the patterns (both over space and time) of disease risks and to quantify uncertainty. The study offers a disease and health outcome surveillance methodology for flexible and efficient exploration and assessment of emerging risk trends and clustering. The methods are motivated and illustrated through a Bayesian analysis of adverse medical events (also known as iatrogenic injuries) among hospitalized elderly patients in British Columbia, Canada. PMID- 17357990 TI - Drug-drug interaction prediction: a Bayesian meta-analysis approach. AB - In drug-drug interaction (DDI) research, a two drug interaction is usually predicted by individual drug pharmacokinetics (PK). Although subject-specific drug concentration data from clinical PK studies on inhibitor/inducer or substrate's PK are not usually published, sample mean plasma drug concentrations and their standard deviations have been routinely reported. In this paper, an innovative DDI prediction method based on a three-level hierarchical Bayesian meta-analysis model is developed. The first level model is a study-specific sample mean model; the second level model is a random effect model connecting different PK studies; and all priors of PK parameters are specified in the third level model. A Monte Carlo Markov chain (MCMC) PK parameter estimation procedure is developed, and DDI prediction for a future study is conducted based on the PK models of two drugs and posterior distributions of the PK parameters. The performance of Bayesian meta-analysis in DDI prediction is demonstrated through a ketoconazole-midazolam example. The biases of DDI prediction are evaluated through statistical simulation studies. The DDI marker, ratio of area under the concentration curves, is predicted with little bias (less than 5 per cent), and its 90 per cent credible interval coverage rate is close to the nominal level. Sensitivity analysis is conducted to justify prior distribution selections. PMID- 17357991 TI - The design of simulation studies in medical statistics by Andrea Burton, Douglas G. Altman, Patrick Royston and Roger L. Holder, Statistics in Medicine 2006; 25:4279-4292. PMID- 17357992 TI - Comparison of the likelihood ratios of two binary diagnostic tests in paired designs. AB - The performance of two binary diagnostic tests is traditionally compared by their respective sensitivities and specificities. Other measures to describe the performance of a binary diagnostic test are likelihood ratios, defined as the ratio between the likelihood of a diagnostic test result in a group of diseased patients and the likelihood of a diagnostic test result in a group of non diseased patients. In this study, we propose a method, based on the log transformation of the ratio of the likelihood ratios, to compare the likelihood ratios of two binary diagnostic tests in paired designs. We have deduced hypothesis tests to compare the likelihood ratios and we have carried out simulation experiments to study the power and the type I error of the hypothesis tests deduced. We have also deduced a joint hypothesis test to simultaneously compare the likelihood ratios. The procedure used has been extended to the situation in which more than two binary diagnostic tests are applied to the same sample, and the situation in which two diagnostic tests with multilevel results are compared. PMID- 17357993 TI - Interval estimation for individual categories in cumulative logit models. AB - We derive and compute confidence intervals for probabilities of categories for ordinal responses in cumulative logit link models using frequentist, Bayesian, and bootstrap approaches. The three approaches are evaluated by their coverage probabilities and are illustrated for longitudinal assessment of graded heart valve prosthesis regurgitation following aortic valve replacement. PMID- 17357994 TI - An investigation of two multivariate permutation methods for controlling the false discovery proportion. AB - Identifying genes that are differentially expressed between classes of samples is an important objective of many microarray experiments. Because of the thousands of genes typically considered, there is a tension between identifying as many of the truly differentially expressed genes as possible, but not too many genes that are not really differentially expressed (false discoveries). Controlling the proportion of identified genes that are false discoveries, the false discovery proportion (FDP), is a goal of interest. In this paper, two multivariate permutation methods are investigated for controlling the FDP. One is based on a multivariate permutation testing (MPT) method that probabilistically controls the number of false discoveries, and the other is based on the Significance Analysis of Microarrays (SAM) procedure that provides an estimate of the FDP. Both methods account for the correlations among the genes. We find the ability of the methods to control the proportion of false discoveries varies substantially depending on the implementation characteristics. For example, for both methods one can proceed from the most significant gene to the least significant gene until the estimated FDP is just above the targeted level ('top-down' approach), or from the least significant gene to the most significant gene until the estimated FDP is just below the targeted level ('bottom-up' approach). We find that the top-down MPT based method probabilistically controls the FDP, whereas our implementation of the top-down SAM-based method does not. Bottom-up MPT-based or SAM-based methods can result in poor control of the FDP. PMID- 17357995 TI - Item reduction in a scale for screening. AB - This paper presents a non-parametric approach for the selection of items in a scale for screening, with the score defined as the sum of item response indicators. Without specifying parametric models for binary classification probabilities, the proposed item selection method evaluates the change in classification accuracy due to adding or deleting one item for a scale with k items. It first removes least useful items from the scale and then uses a forward stepwise selection procedure to the remaining items to identify a subset of items for a reduced scale. The reduced scale usually retains or improves classification accuracy compared to the full scale. The variation in items selected can be assessed with bootstrap samples. In a simulation study, the proposed procedure shows a fairly good finite sample performance. The method is illustrated with a data set on patients with and without high risk of developing Alzheimer's disease who were administered a 40-item test of olfactory function. PMID- 17357996 TI - Vascular proliferations of the skin after radiation therapy for breast cancer: clinicopathologic analysis of a series in favor of a benign process: a study from the French Sarcoma Group. AB - BACKGROUND: Cutaneous vascular proliferations that occur in the field of prior radiotherapy include angiosarcoma and small, cutaneous lesions with a pseudosarcomatous pattern that previously were reported as atypical vascular lesions or benign lymphangiomatous papules. METHODS: The objective of this study was to investigate the clinicopathologic features and outcomes of 56 radiation induced vascular proliferations that occurred in 36 patients who received previous treatment for breast carcinoma. Data from all patients were retrieved from the files of the French Sarcoma Group. Immunostaining with D2.40 antibody was performed in 24 lesions. RESULTS: All patients (median age, 52 years) had received external radiotherapy. Small papules developed within the field of prior radiotherapy (median latency interval, 66 months). Microscopically, the lesions were relatively well circumscribed, and they were located mostly in the superficial/middermis. They were composed of dilated or irregular-jagged vascular channels that were lined by a single layer of bland endothelial cells, and they demonstrated either a predominately lymphangioendothelioma-like or lymphangioma/lymphangioma circumscriptum-like growth pattern. Micropapillary tufts were common findings. Ten lesions showed additional cytologic and/or architectural atypia. Twenty of 24 lesions showed D2.40 positivity. Follow-up information was available for 31 patients (median follow-up, 48 months): Five women developed new cutaneous lesions, and 1 woman had spontaneous regression of her lesions. None of the patients developed cutaneous angiosarcoma. Five patients were lost to follow-up. CONCLUSIONS: Although vascular proliferations in irradiated skin may mimic angiosarcoma morphologically, the large majority of these lesions showed a benign clinical outcome. Despite relatively limited follow up, the current results indicate the benign nature of these vascular proliferations. PMID- 17357998 TI - Long-term outcome of hematuria home screening for bladder cancer in men. PMID- 17357999 TI - The definition of humeral torsion: a comment on Rhodes (2006). PMID- 17358001 TI - Glucocorticoid levels in free ranging resident mantled howlers: a study of coping strategies. AB - A growing amount of data shows that a preference for passive-nonaggressive over active-aggressive problem solving is associated with higher levels of glucocorticoids (GC). For mantled howlers, the arrival of an adult male in a new group is a potential source of psychological stress for both resident males and females. Resident mantled howler males take an active stand and aggressively repel the entrance of solitary males, while females take a passive-nonaggressive stand. In order to study whether the relationship between coping strategies and the activation of the hypothalamic-pituitary-adrenal (HPA) axis observed in other species applies to the response of resident mantled howlers to the presence of solitary males, we examine the relationship between different group and subpopulation variables and the GC levels measured in feces collected from 10 groups living in six forest fragments, in Los Tuxtlas, Mexico. The results of our study suggest that the resident mantled howler females' passive response to the presence of solitary males is accompanied by the activation of the HPA axis, whereas resident males' aggressive response is not accompanied by any changes in the HPA axis. In contrast, a previous study suggests that resident male howlers respond by increasing their testosterone levels to the presence of solitary males (Cristobal-Azkarate et al., Hormones and Behavior 2006;49 261-267). These different behavioral and hormonal responses coincide with the active and passive coping styles described for other species. The conditions in which howlers live in our study area may be favoring the interaction between solitary and resident howlers, and inducing chronically high GC levels, which in turn could negatively affect the fitness of these subpopulations. PMID- 17358002 TI - Development and evolution of chordate cartilage. AB - Deuterostomes are a monophyletic group of animals containing vertebrates, lancelets, tunicates, hemichordates, echinoderms, and xenoturbellids. Four out of these six extant groups-vertebrates, lancelets, tunicates, and hemichordates-have pharyngeal gill slits. All groups of deuterostome animals that have pharyngeal gill slits also have a pharyngeal skeleton supporting the pharyngeal openings, except tunicates. We previously found that pharyngeal cartilage in hemichordates and cephalochordates contains a fibrillar collagen protein similar to vertebrate type II collagen, but unlike vertebrate cartilage, the invertebrate deuterostome cartilages are acellular. We found SoxE and fibrillar collagen expression in the pharyngeal endodermal cells adjacent to where the cartilages form. These same endodermal epithelial cells also express Pax1/9, a marker of pharyngeal endoderm in vertebrates, lancelets, tunicates, and hemichordates. In situ experiments with a cephalochordate fibrillar collagen also showed expression in pharyngeal endoderm, as well as the ectoderm and the mesodermal coelomic pouches lining the gill bars. These results indicate that the pharyngeal endodermal cells are responsible for secretion of the cartilage in hemichordates, whereas in lancelets, all the pharyngeal cells surrounding the gill bars, ectodermal, endodermal, and mesodermal may be responsible for cartilage formation. We propose that endoderm secretion was primarily the ancestral mode of making pharyngeal cartilages in deuterostomes. Later the evolutionary origin of neural crest allowed co-option of the gene network for the secretion of pharyngeal cartilage matrix in the new migratory neural crest cell populations found in vertebrates. PMID- 17358003 TI - Atherosclerosis and dementia: leading by association. PMID- 17358004 TI - Changes in cortical excitability differentiate generalized and focal epilepsy. AB - OBJECTIVE: Different pathophysiological mechanisms related to the balance of cortical excitatory and inhibitory influences may underlie focal and generalized epilepsies. We used transcranial magnetic stimulation to search for interictal excitability differences between patients with idiopathic generalized epilepsy (IGE) and focal epilepsy. METHODS: Sixty-two drug-naive patients with newly diagnosed epilepsy (35 IGE, 27 focal epilepsy) were studied. In the latter group, the seizure focus was not located in the motor cortex. Motor threshold at rest, cortical silent period threshold, recovery curve analysis using paired-pulse stimulation at a number of interstimulus intervals), and cortical silent period were determined. Results were compared with those of 29 control subjects. RESULTS: Hyperexcitability was noted in the recovery curves at a number of interstimulus intervals in both hemispheres in patients with IGE and in the hemisphere ipsilateral to the seizure focus in those with focal epilepsy compared with control subjects and the contralateral hemisphere in focal epilepsy. Motor threshold and cortical silent period threshold were higher in the ipsilateral hemisphere in focal epilepsy compared with the contralateral hemisphere. No other intragroup or intergroup differences were found in the other measures. INTERPRETATION: The disturbance of cortical excitatory/inhibitory function was found to be bilateral in IGE, whereas in focal epilepsy it spread beyond the epileptic focus but remained lateralized. This finding confirms that there are differences in cortical pathophysiology comparing the two major types of epilepsy. PMID- 17358005 TI - Proteomic discovery of CSF biomarkers for Alzheimer's disease. PMID- 17358006 TI - Sympathetic neural activity, sex dimorphism, and postural tachycardia syndrome. AB - OBJECTIVE: To elucidate the mechanisms whereby postural tachycardia syndrome (POTS) patients maintain orthostatic blood pressure and explain the greater prevalence of female cases in POTS cohorts. METHODS: We investigated muscle sympathetic nerve (MSN) discharge characteristics in 12 female POTS patients and in 9 male and 12 female control subjects using the burst amplitude distribution and the relative contribution of burst frequency and burst amplitude. RESULTS: At rest, burst distribution was shifted toward larger amplitudes in POTS patients (p < 0.005), consistent with increased sympathetic activity. During hypotension, the distribution shifted toward larger amplitude bursts in control subjects (p < 0.001), whereas it did not change in POTS patients. Total MSN activity increase to hypotension did not differ between subject groups, but the relative contribution of burst frequency change to the total activity increase was greater in POTS patients than in female (p < 0.05) and male (p < 0.001) control subjects. In contrast, the relative contribution of burst amplitude change to total MSN activity increase was greater in male compared with female control subjects (p < 0.05) and POTS patients (p < 0.001). INTERPRETATION: At rest, the burst amplitude distribution was consistent with increased sympathetic activity in POTS and did not change in response to hypotension. In response to hypotension, burst frequency makes a proportionally greater contribution to the increase in total MSN activity in POTS patients compared with female control subjects, and female compared with male control subjects. These physiological differences in MSN discharge characteristics, in the setting of sympathetic fiber loss associated with POTS, may contribute to the predisposition to and greater prevalence of POTS in female individuals. PMID- 17358007 TI - The function of teeth chattering in male Barbary macaques (Macaca sylvanus). AB - Teeth chattering is seen in many primate species and has been proposed to have a range of social functions. This observational study tested specific hypotheses relating to the function of teeth chattering in a semi-free-ranging group of Barbary macaques, Macaca sylvanus. During focal watches of males, the outcome of male-male dyadic social interactions in which teeth chattering was present or absent was compared. Using these data, we tested the predictions of four hypotheses: teeth chattering functions as a signal of submission, appeasement, affiliation or reassurance. Support was found for all four hypotheses. In addition, in some contexts, an exchange of teeth chattering appeared to have a greater impact on the outcome of interactions than one male alone giving this signal. These findings suggest that teeth chattering serves an important role in coordinating the social interactions of male Barbary macaques. PMID- 17358008 TI - Promoter polymorphisms in the MATP (SLC45A2) gene are associated with normal human skin color variation. AB - Human pigmentation is a complex physical trait in which the membrane-associated transporter protein (MATP) plays an important role as it is involved in intracellular processing and trafficking of melanosomal proteins. Recently, pathogenic mutations in MATP have been shown to cause oculocutaneous albinism type 4, while other polymorphisms are known to have a role in normal pigmentation variation. We previously reported significant associations of two coding region polymorphisms with hair, skin, and eye color in Caucasians. Here we characterize the promoter region of MATP identifying two new transcription start sites and a novel duplication (c.-1176_-1174dupAAT). A total of 700 individuals from five different population groups (529 Caucasians, 38 Asians, 46 African Americans, 47 Australian Aborigines, and 40 Spanish Basques) were genotyped for known promoter polymorphisms c.-1721C>G (rs13289) and c.-1169G>A (rs6867641), as well as c. 1176_-1174dupAAT. Allele frequencies of all three polymorphisms were significantly different between population groups. In Caucasians, the -1721G, +dup, and -1169A alleles were significantly associated with olive skin color. The three promoter polymorphisms were found to be in linkage disequilibrium with each other but not with the two previously reported coding region polymorphisms. Functional analyses in a melanoma cell line showed that the promoter haplotype 1721G, +dup, -1169A significantly decreased MATP transcription. This report provides further evidence for the involvement of MATP in normal pigmentation variation by identifying associations between MATP alleles and skin color variation in Caucasians and demonstrating a functional significance of these polymorphisms. PMID- 17358009 TI - Habitat fragmentation and population size of the black and gold howler monkey (Alouatta caraya) in a semideciduous forest in Northern Argentina. AB - A population of black and gold howler monkeys (Alouatta caraya) living near the southern limit of its distribution in a semideciduous forest located in northern Argentina was studied in 2003 to evaluate the possible effects of habitat fragmentation - owing to logging - on its density and social organization within it. Aerial photographs taken in 1982, 1992, and 2001 were used to compare maps of vegetation. These maps were used to evaluate changes in the area covered by forest fragments. From March to June 2003, 10-day monthly surveys of howlers were made in each fragment. A total of 232 individual howlers were counted, belonging to 34 groups plus a solitary adult female. Groups ranged from 2 to 19 individuals (mean = 6.82, SD = 4.23), and 21% of the groups contained more than one adult male. Adults accounted for 55% of the individuals, immatures for 45%, and infants represented 13% of the total. Data obtained were compared with information available for the same population for 1982 and 1995. Results revealed no significant changes in the area of fragments, the crude and ecological density of howlers, and group composition. Group sizes and group composition of howlers suggest that the population remained stable over the past 22 years. The density, number of groups, and individuals appears not to be affected by fragmentation and logging, but crude density was low compared with other less-disturbed habitats. The status of the population remains uncertain owing to isolation, and because there are no protected areas to ensure its stability for the future. PMID- 17358010 TI - Tree and forest characteristics influence sleeping site choice by golden lion tamarins. AB - Lion tamarin monkeys are among a small number of primates that repeatedly use a few tree holes for the majority of their sleeping sites. To better understand why lion tamarins rely on tree holes as sleeping sites, we compared the physical characteristics of frequently used sleeping sites, infrequently used sleeping sites, and randomly selected forest locations at multiple spatial scales. From 1990 to 2004, we recorded 5,235 occurrences of sleeping site use by 10 groups of golden lion tamarins (Leontopithecus rosalia) in Poco das Antas Reserve, Rio de Janeiro State, Brazil. Of those, 63.6% were tree holes. Bamboo accounted for an additional 17.5% of observations. Frequently used tree holes were more likely to be found in living trees and their entrances were at lower canopy heights than infrequently used tree holes. We also found that frequently used sleeping sites, in comparison to random sites, were more likely to be found on hillsides, be close to other large trees, have a lower percent of canopy cover, and have larger diameter at breast height. Topography and small-scale variables were more accurate than were habitat-level classifications in predicting frequently used sleeping sites. There are ample tree holes available to these lion tamarins but few preferred sites to which they return repeatedly. The lion tamarins find these preferred sites wherever they occur including in mature forest and in relics of older forest embedded in a matrix of secondary forest. PMID- 17358011 TI - Evaluation of the vervet (Clorocebus aethiops) as a model for the assisted reproductive technologies. AB - The vervet monkey was evaluated as a primate model for use in assisted reproductive technologies (ARTs). Eight adult female vervets were hormonally monitored for their potential use as egg donors and those six females displaying regular menstrual cycles were subjected to controlled ovarian stimulation with recombinant human gonadotropins. Three animals failed to respond while laparoscopic follicular aspiration was performed on the other three females at 27 30 h post-human chorionic gonadotropin administration. A total of 62, 40, and 18 oocytes was recovered from these three animals of which 30, 20, and 4, respectively, matured to the metaphase II stage and were subsequently inseminated using intracytoplasmic sperm injection. An average of 40+/-15% (SEM) of the inseminated oocytes were fertilized based on pronucleus formation and timely cleavage. One embryo from each of the two stimulated females developed into expanded blastocysts. Two adult male vervets were assessed as sperm donors. Neither adjusted well to the restraint and collection procedure required for penile electroejaculation. Samples collected via rectal electroejaculation were very low in sperm motility and concentration; however, cauda epididymal aspirations from one male yielded an adequate concentration of motile sperm. These results emphasize the need to establish species-specific ovarian stimulation protocols and semen collection techniques if vervets are to be considered for basic and applied (ARTs) research on primate gametes or embryos. PMID- 17358012 TI - Evidence for positive and negative regulation of the mouse Cdx2 gene. AB - The caudal family of transcription factors specifies posterior structures during mouse development. We describe the cis-regulatory regions that control mouse Cdx2 expression in the posterior neural tube and mesoderm. An 11.4 kb genomic fragment directs reporter gene expression in a pattern reflecting endogenous Cdx2 expression. A crucial enhancer is located in a 1 kb fragment upstream of the Cdx2 transcriptional start site. This enhancer by itself directs reporter gene expression to more anterior levels in the neural tube compared to the endogenous Cdx2 expression, suggesting the presence of negative regulatory elements outside the 1 kb fragment. A second enhancer, located in the first intron directs robust expression to the posterior two-thirds of the developing embryo in a pattern that is ectopic to Cdx2 expression. The intronic enhancer activity is silenced in the context of the larger 11.4 kb reporter construct. Intron 1 contains two independent enhancers that specifically direct expression to mesoderm (MSE) and neural tube (NSE). Phylogenetic comparison of vertebrate Cdx2 sequences indicates several conserved regions of sequences within the three-enhancer regions. A transcription factor database search suggests potential binding sites for factors involved in FGF and Wnt signaling pathways. PMID- 17358013 TI - Using zebrafish to investigate cypriniform evolutionary novelties: functional development and evolutionary diversification of the kinethmoid. AB - Although the zebrafish has become a popular model organism for biomedical studies, we propose that the wealth of morphological novelties that characterize this cypriniform fish makes it well suited for investigating the development of evolutionary innovations. Morphological novelties associated with feeding in cypriniform fishes include: a unique structure of the pharyngeal jaws in which the lower pharyngeal jaws are enlarged and opposed to a pad on the basioccipital process; a palatal organ found on the roof of the buccal chamber that is thought to help process detrital food within the buccal chamber; and, the kinethmoid, a novel ossification that effects a unique means of premaxillary protrusion. We present new morphological and developmental data and review functional data regarding the role of the kinethmoid in premaxillary protrusion in the zebrafish. Premaxillary protrusion plays an important role in effective prey acquisition in teleosts and the evolution of a unique means of premaxillary protrusion within Cypriniformes may have led to a number of trophic radiations within this clade. Ontogenetic data from zebrafish show that substantial premaxillary protrusion is not seen until these fish have undergone metamorphosis at which point the adductor mandibulae musculature becomes divided and all ligamentous attachments become established. A comparative study of families within Cypriniformes shows diverse morphologies of the kinethmoid. The morphological diversification that characterizes the kinethmoid suggests that this feeding structure has played a role in trophic radiations within Cypriniformes, since the morphology of this feature is correlated with feeding habits. PMID- 17358014 TI - Polyandry and female control: the red flour beetle Tribolium castaneum as a case study. AB - Females of many animal species are polyandrous, and there is evidence that they can control pre- and post-mating events. There has been a growing interest in consequences of polyandry for male and female reproductive success and offspring fitness, and its evolutionary significance. In several taxa, females exhibit mate choice both before and after mating and can influence the paternity of their offspring, enhancing offspring number and quality, but potentially countering male interests. Studying female mating biology and in particular post-copulatory female control mechanisms thus promises to yield insights into sexual selection and the potential of male-female coevolution. Here, we highlight the red flour beetle Tribolium castaneum (Herbst), a storage pest, as a model system to study polyandry, and review studies addressing the effects of polyandry on male sperm competitive ability and female control of post-mating events. These studies show that the outcome of sperm competition in the red flour beetle is influenced by both male and female traits. Furthermore, recent advances suggest that sexual conflict may have shaped reproductive traits in this species. PMID- 17358015 TI - Morphing the hyomandibular skeleton in development and evolution. AB - How might changes in developmental regulatory pathways underlie evolutionary changes in morphology? Here we focus on a particular pathway regulated by a secreted, signaling peptide, Endothelin1 (Edn1). Developmental genetic analyses show the Edn1-pathway to be crucial for hyomandibular patterning, and we discuss our work with zebrafish suggesting how the signal may function in regulating numbers of skeletal elements, their sizes and their shapes. We then review a broader collection of comparative studies that examine morphological evolution of a subset of the same skeletal elements-the opercular-branchiostegal series of bones of the hyoid arch. We find that phenotypic changes in zebrafish mutants copy evolutionary changes that recur along many actinopterygian lineages. Hence the developmental genetic studies are informative for providing candidate pathways for macroevolution of facial morphology, as well as for our understanding of how these pathways work. PMID- 17358016 TI - Mining of putative cis-acting elements for chromatin mediated regulation of Hox genes in mammals by in-silico analysis. AB - The remarkable conservation in developmental strategies across phyla is well reflected in the conservation of the homeotic gene complexes responsible for establishing the body plan in embryonic development. On the other hand, changes in the strategy of transcription regulation are believed to form one of the major factors in the evolution of developmental mechanisms and phenotypic evolution of species. Apart from transcription regulation by gene specific transcription factors, the role of regulators mediating modifications of chromatin proteins, especially of HOX gene clusters in Drosophila is well documented. By comparative genomics we have identified novel motifs conserved in mouse, chimpanzee and human in the noncoding upstream/intronic sequences of Hox genes by in silico analysis. These motifs lack the binding sites for known transcription factors and are significantly over represented in the target genes of one of the core components of Polycomb Repressive Complex namely Supressor of zeste 12 (SUZ12) in human embryonic cells reported by Lee et al. [2006a. Cell 125:301-313]. Therefore, we predict that they could be the sites of interaction of chromatin modifying complexes for epigenetic regulation. PMID- 17358017 TI - Early developmental plasticity and integrative responses in arctic charr (Salvelinus alpinus): effects of water velocity on body size and shape. AB - Environmental conditions such as temperature and water velocity may induce changes among alternative developmental pathways, i.e. phenotypic responses, in vertebrates. However, the extent to which the environment induces developmental plasticity and integrated developmental responses during early ontogeny of fishes remains poorly documented. We analyzed the responses of newly hatched Arctic charr (Salvelinus alpinus) to four experimental water velocities during 100 days of development. To our knowledge, this work is the first to analyze developmental plasticity responses of body morphology to an experimental gradient of water velocities during early ontogeny of fish. Arctic charr body size and shape responses show first, that morphometric traits display significant differences between low and high water velocities, thus revealing directional changes in body traits. Secondly, trait variation allows the recognition of critical ontogenetic periods that are most responsive to environmental constraints (40-70 and 80-90 days) and exhibit different levels of developmental plasticity. This is supported by the observation of asynchronous timing of variation peaks among treatments. Third, morphological interaction of traits is developmentally plastic and time dependent. We suggest that developmental responses of traits plasticity and interaction at critical ontogenetic periods are congruent with specific environmental conditions to maintain the functional integrity of the organism. PMID- 17358018 TI - Female feeding priority in bonobos, Pan paniscus, and the question of female dominance. AB - The question of whether bonobos show feeding priority and female dominance has been proposed and examined, both in the wild and in captive studies, with differing results. The relationship between female dominance and female feeding priority has been best studied in prosimian primates. These studies use established criteria of females consistently evoking submissive behavior from males in dyadic encounters for determining female dominance. Although the relationship is complex, female dominance in prosimians is associated with preferential access to food. Data from studies of wild habituated bonobos in the Lomako Forest, Democratic Republic of the Congo, are examined for evidence of both female feeding priority and female social dominance using similar criteria as used for prosimians. Bonobos showed evidence of female feeding priority in small, but not in large, food patches. Male-male competition for mating opportunities at the start of the food bout was related to some, but not all, differences in time spent feeding between the sexes. Female dominance similar to that seen in prosimians was not observed in these bonobos. Males were consistently dominant in dyadic interactions. Female feeding priority with male dyadic social dominance implies that male deference during feeding cannot be excluded as one explanation of interpretations of female dominance in bonobos. Additionally, dominance of male bonobos by females appears to require the presence of female coalition partners. As in other primates with female feeding priority, bonobo females express this trait where food is economically defendable. Unlike prosimians, however, bonobo female feeding priority may result from male deference and the importance of female coalitions in nondyadic interactions. PMID- 17358019 TI - Medial temporal lobe activity at recognition increases with the duration of mnemonic delay during an object working memory task. AB - Object working memory (WM) engages a disseminated neural network, although the extent to which the length of time that data is held in WM influences regional activity within this network is unclear. We used functional magnetic resonance imaging to study a delayed matching to sample task in 14 healthy subjects, manipulating the duration of mnemonic delay. Across all lengths of delay, successful recognition was associated with the bilateral engagement of the inferior and middle frontal gyri and insula, the medial and inferior temporal, dorsal anterior cingulate and the posterior parietal cortices. As the length of time that data was held in WM increased, activation at recognition increased in the medial temporal, medial occipito-temporal, anterior cingulate and posterior parietal cortices. These results confirm the components of an object WM network required for successful recognition, and suggest that parts of this network, including the medial temporal cortex, are sensitive to the duration of mnemonic delay. PMID- 17358020 TI - FMRI activations of amygdala, cingulate cortex, and auditory cortex by infant laughing and crying. AB - One of the functions of emotional vocalizations is the regulation of social relationships like those between adults and children. Listening to infant vocalizations is known to engage amygdala as well as anterior and posterior cingulate cortices. But, the functional relationships between these structures still need further clarification. Here, nonparental women and men listened to laughing and crying of preverbal infants and to vocalization-derived control stimuli, while performing a pure tone detection task during low-noise functional magnetic resonance imaging. Infant vocalizations elicited stronger activation in amygdala and anterior cingulate cortex (ACC) of women, whereas the alienated control stimuli elicited stronger activation in men. Independent of listeners' gender, auditory cortex (AC) and posterior cingulate cortex (PCC) were more strongly activated by the control stimuli than by infant laughing or crying. The gender-dependent correlates of neural activity in amygdala and ACC may reflect neural predispositions in women for responses to preverbal infant vocalizations, whereas the gender-independent similarity of activation patterns in PCC and AC may reflect more sensory-based and cognitive levels of neural processing. In comparison to our previous work on adult laughing and crying, the infant vocalizations elicited manifold higher amygdala activation. PMID- 17358021 TI - Do chimpanzees build comfortable nests? AB - Nests built by wild chimpanzees (Pan troglodytes verus) were studied at the Fongoli research site in southeastern Senegal from January 2004-May 2004 to investigate the role of comfort in nest building behavior by relating measures of nest comfort and building effort. Nest comfort across zones of the nest surface were compared with construction effort for 25 nests. Several variables of nest comfort were assessed: (1) physical discomfort, (2) visible discomfort, and (3) softness. Physical discomfort was used as a representative measure of nest discomfort. Building effort was measured by (1) construction force, (2) complexity, and (3) added material. Spearman rank correlations compared Effort and Comfort measures for both whole nests and central versus edge zones. The results show that construction force and complexity do not influence comfort of the nest as a whole. Greater Construction force correlates with more nest edge discomfort, yet the central area shows no difference. More complex nests do result in a more comfortable central area in the nest. Nests built with greater force may result in more discomfort, whereas complexity may allow chimpanzees to maintain comfort in a central area for sleep. Chimpanzees may place additional leaves or twigs over hard branches, protruding from the nest surface after construction, to increase comfort of the central nest area. Functions of chimpanzee nest building are likely to be several, but these results suggest comfort is a factor in nest building behavior. PMID- 17358022 TI - Vegetative predictors of primate abundance: utility and limitations of a fine scale analysis. AB - Determining ecological predictors of primate abundance is important for both theoretical and applied conservation management. For forest primates, research has focused on comparisons of primate abundance and vegetation in different forest blocks or forest compartments with different management histories. However, great variation in primate abundance often occurs within single forests, especially in mountainous areas or in areas with habitat mosaics due to past disturbance. Here we assess, for the first time, the usefulness and limitations of small-scale, within-transect analysis of vegetative parameters as predictors of primate abundance in a very heterogeneous forest habitat in the Udzungwa Mountains of Tanzania. Relative abundance of four species of diurnal primates was recorded over a period of 2.5 years by walking three census transects 48 times each. Tree size, density, species composition, and food plants were measured along the same census lines. The fine-scale relationship between primate abundance and vegetative variables was analyzed through generalized linear modeling applied to 58 segments of these three census lines. Each segment was 200 m in length. For all four primate species, we found significant associations between their abundance and selected vegetative variables. The abundance of the endemic and endangered Udzungwa red colobus Procolobus gordonorum was positively related to mean basal area of large trees (diameter at breast height greater than 20 cm) and to the species richness of their food plants. Considering the very great variation in primate abundance that was recorded among segments of the census lines, our approach proved useful in predicting the relationship between primate abundance and small-scale habitat differences. The main limitation of this study, however, was the relatively low-predictive power of the models for some species, especially the Angolan colobus Colobus angolensis. We discuss the potential reasons for this problem and suggest possible improvements for future studies. PMID- 17358023 TI - Washington statewide pathology surveillance for prion disease. AB - In February 2004, we initiated an epidemiological investigation within a US state to enhance autopsy surveillance for clinically suspected prion disease. During the first 30 months, 30 cases of suspected prion disease were referred from throughout Washington. Of these, 18 cases had prion disease, and all of these were classified as either familial or sporadic Creutzfeldt-Jakob disease (CJD); there was no case of variant CJD. This represents a death rate of approximately 1.1 cases of sporadic CJD per 1 million people per year in Washington. Our results do not support the hypotheses that variant CJD is an emerging illness in Washington or that sporadic CJD is more common in this state than in other regions of the world. PMID- 17358024 TI - Plasma and cellular markers of 3'-azido-3'-dideoxythymidine (AZT) metabolism as indicators of DNA damage in cord blood mononuclear cells from infants receiving prepartum NRTIs. AB - Several systemic and cellular markers of 3'-azido-3'-dideoxythymidine (AZT) metabolism and AZT incorporation into nuclear DNA were measured in cord blood from uninfected infants born to HIV-1-infected mothers receiving prepartum therapies based on AZT or AZT in combination with 2',3'-dideoxy-3'-thiacytidine (3TC). In addition, the relationships among these pharmacological end points, levels of AZT-DNA incorporation, and the previously reported mutagenic responses in these infants were evaluated. AZT- and 3TC-specific radioimmunoassays (RIAs), or HPLC coupled with AZT-RIA, were used to measure plasma levels of AZT and the AZT-glucuronide, and cellular levels of AZT, phosphorylated AZT, and DNA incorporation of AZT or 3TC in cord blood mononuclear cells from treated infants compared with unexposed controls born to HIV-uninfected mothers. Fewer infants had detectable AZT-DNA incorporation levels in the group exposed to AZT (71%; n = 7) compared with those receiving AZT-3TC (100%; n = 21), and the mean AZT-DNA incorporation for AZT-exposed infants (14.6 +/- 6.3 AZT/10(6) nucleotides) was significantly lower than that in AZT-3TC exposed infants (51.6 +/- 10.2 AZT/10(6) nucleotides; P = 0.028). Low levels of 3TC-DNA incorporation found in a few AZT 3TC-exposed newborns correlated with AZT-DNA incorporation values in the same samples. Among the metabolites studied, there were positive correlations between levels of AZT-diphosphate and AZT-triphosphate, and AZT-triphosphate and AZT-DNA incorporation, in nucleoside analog-exposed infants. Levels of AZT-DNA incorporation, however, did not correlate well with the reported frequencies of somatic mutations in the same population of nucleoside analog-treated children. While these data support the continued use of AZT-based therapies during pregnancy, infants receiving prepartum AZT should be monitored long-term for adverse health effects. PMID- 17358025 TI - Special issue on health risks of perinatal exposure to nucleoside reverse transcriptase inhibitors. PMID- 17358026 TI - Transplacental carcinogenicity of 3'-azido-3'-deoxythymidine in B6C3F1 mice and F344 rats. AB - The prophylactic use of zidovudine (3'-azido-3'-deoxythymidine, AZT) during pregnancy greatly reduces transmission of HIV-1 from infected mothers to their infants; however, the affinity of host cell DNA polymerases for AZT also allows for its incorporation into host cell DNA, predisposing to cancer development. To expand upon previous transplacental carcinogenesis assays performed in CD-1 mice, the transplacental carcinogenicity of AZT was evaluated in a second mouse strain and a second rodent species. Date-mated female mice and rats were gavaged daily with 0, 80, 240, or 480 mg AZT/kg bw during the last 7 days of gestation. At 2 years postpartum, male and female B6C3F1 mouse and F344 rat offspring (n = 44-46 of each sex and species/treatment group) were necropsied for gross and microscopic tissue examinations. Under the conditions of these two-year studies, there was clear evidence of carcinogenic activity based upon significant dose related trends and increases in the incidences of hemangiosarcoma in male mice and mononuclear cell leukemia in female rats. There was some evidence of carcinogenic activity in the livers of male mice based upon a positive trend and an increased incidence of hepatic carcinoma in the high-dose AZT group. The incidence of gliomas in female rats exceeded the historical background rates for gliomas in F344 rats. P53 overexpression was detected in some AZT-treated mouse neoplasms. These and other cancer-related findings confirm and extend those of previous transplacental carcinogenicity studies of AZT in mice, support the need for long-term follow-up of nucleoside reverse transcriptase inhibitor (NRTI) exposed children, and indicate the necessity for effective protective strategies against NRTI-induced side effects. PMID- 17358027 TI - Genotoxicity assessed by the comet and GPA assays following in vitro exposure of human lymphoblastoid cells (H9) or perinatal exposure of mother-child pairs to AZT or AZT-3TC. AB - The genotoxicity of zidovudine (AZT) based treatments was investigated in human H9 lymphoblastoid cells in an in vitro study and in red blood cells (RBCs) from perinatally exposed HIV-1-infected mothers and their infants in an observational cohort study. Exposure of H9 cells for 24 hr to AZT produced dose-dependent increases in Comet assay tail moment (TM) when electrophoresed at pH 13.0, but not at pH 12.1 or pH 8.0, suggesting that DNA damage was via alkali-labile lesions and not double-stranded DNA strand breaks. The TM dose response at pH 13.0 correlated directly with AZT-DNA incorporation determined by AZT radioimmunoassay. Levels of DNA damage in utero, measured by Comet assay TM, were similar in cord blood mononuclear cells of nucleoside analog-exposed newborns (n = 43) and unexposed controls (n = 40). In contrast, the glycophorin A (GPA) somatic cell mutation assay (which screens for large-scale DNA damage in RBCs) showed clear evidence that GPA N/N variants, arising from chromosome loss and duplication, somatic recombination, and gene conversion, were significantly elevated in mother-child pairs receiving prepartum AZT plus lamivudine (3TC). Cord blood from newborns exposed to AZT-3TC had GPA N/N variant frequencies of 4.7 +/- 0.7 (mean +/- SE) x 10(-6) RBCs (n = 26 infants) compared with 2.2 +/- 0.3 x 10(-6) RBCs for unexposed controls (n = 30 infants; P < 0.001). Elevations in GPA N/N variants generally persisted through 1 year of age in nucleoside analog-exposed children. Overall, the mutagenic effects found in mother-child pairs receiving AZT-based treatments justify their surveillance for long-term genotoxic consequences. PMID- 17358028 TI - Does perinatal antiretroviral therapy create an iatrogenic cancer risk? AB - Antiretroviral therapy is highly effective in reducing vertical transfer of HIV infection, sparing many thousands of children premature death from AIDS. However, accumulating evidence indicates that perinatal exposure to antiretroviral agents may place them at elevated risk of developing cancer later in life, owing to potential carcinogenic effects of the agents. An initial experimental evaluation clearly demonstrated that AZT was a genotoxin and transplacental carcinogen of intermediate potency in CD-1 mice. This issue of Environmental and Molecular Mutagenesis contains reports of recent studies designed to confirm and extend earlier findings, and to provide further perspective that will facilitate development of strategies through which the adverse effects might be mitigated. The studies focused on various aspects of the genotoxicity and carcinogenicity of antiretroviral agents, including: mutagenesis in several in vitro experimental systems; mutations and clastogenic effects induced by transplacental administration in mice; transplacental carcinogenesis and mutations in oncogenes and tumor suppressor genes in tumors of mice; and genotoxicity and clastogenicity following perinatal exposure of HIV-infected mothers and their uninfected infants. Collectively, the results obtained provide convincing biological plausibility for the postulate that perinatal exposure to nucleoside analogs puts children at elevated risk of developing cancers later in life. They further emphasize the importance of continued surveillance of these children for increased cancer risk and indicate a need for efforts to develop less genotoxic alternative agents. PMID- 17358029 TI - Relative mutagenic potencies of several nucleoside analogs, alone or in drug pairs, at the HPRT and TK loci of human TK6 lymphoblastoid cells. AB - Experiments were performed to investigate the impact of didanosine (ddI), lamivudine (3TC), and stavudine (d4T) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using a cell cloning assay for assessing the effects of individual nucleoside analogs (NRTIs)/drug combinations in human TK6 B lymphoblastoid cells. Three-day treatments with 0, 33, 100, or 300 microM ddI, 3TC, or ddI-3TC produced positive trends for increased HPRT and TK mutant frequencies. While dose-related trends were too small to reach significance after treatments with d4T or d4T-3TC, pairwise comparisons with control cells indicated that exposure to 100 microM d4T or d4T-3TC caused significant elevations in HPRT mutants. Measurements of mutagenicity in cells exposed to d4T (or d4T-3TC) were complicated by the cytotoxicity of this NRTI. Enhanced increases in mutagenic responses to combined NRTI treatments, compared with single drug treatments, occurred as additive to synergistic effects in the HPRT gene of cells exposed to 100 microM ddI-3TC or 100 microM d4T-3TC, and in the TK gene of cells exposed to 100 or 300 microM ddI-3TC. Comparisons of these data to mutagenicity studies of other NRTIs in the same system (Meng Q et al. [2000c]: Proc Natl Acad Sci USA 97:12667-126671; Torres SM et al. [2007]: Environ Mol Mutagen) indicate that the relative mutagenic potencies for all drugs tested to date are: AZT-ddI > ddI-3TC > AZT-3TC congruent with AZT-3TC-ABC (abacavir) > AZT >/=ddI > d4T-3TC > 3TC > d4T >/= ABC. These collective data suggest that all NRTIs with antiviral activity against HIV-1 may cause host cell DNA damage and mutations, and impose a cancer risk. PMID- 17358030 TI - Frequency of Hprt mutant lymphocytes and micronucleated erythrocytes in p53 haplodeficient mice treated perinatally with AZT and AZT in combination with 3TC. AB - Azidothymidine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) that is used for reducing mother-to-child transmission of human immunodeficiency virus I. Combinations of AZT and 3'-thiacytidine (3TC) are even more effective than AZT alone. AZT, however, is a mutagen and carcinogen in rodent models and 3TC can increase the genotoxicity of AZT. Since p53 plays a key role in human and mouse tumorigenesis, p53-haplodeficient mice are currently being evaluated as a model for assessing the carcinogenicity of perinatal exposure to NRTIs. In the present study, male C57BL/6 p53(+/+) and p53(-/-) mice were mated with C3H p53(+/+) females; the pregnant females were treated on gestation day 12 through parturition with 40, 80, and 160 mg/kg of AZT or a combination of 160 mg/kg AZT and 100 mg/kg 3TC (AZT-3TC); the p53(+/+) and p53(+/-) offspring were treated daily after birth through postnatal day (PND) 28. The frequencies of micronucleated reticulocytes (MN-RETs) and micronucleated normochromatic erythrocytes (MN-NCEs) were determined on PND1, PND10, and PND28; the frequency of Hprt mutant lymphocytes was measured on PND28. The frequencies of MN-RETs and MN-NCEs were increased in treated animals at all time points; there were no differences in the responses of p53(+/+) and p53(+/-) animals treated with identical doses of NRTIs. After correction for clonal expansion, both AZT and AZT 3TC treatments induced small but significant increases in the frequency of Hprt mutant lymphocytes in p53(+/-) mice, but not in p53(+/+) mice. The data indicate that p53 haplodeficiency affects the genotoxicity of NRTIs; thus, p53(+/-) mice may be a sensitive model for evaluating the carcinogenicity of perinatal exposure to NRTIs. PMID- 17358031 TI - Clinical mitochondrial dysfunction in uninfected children born to HIV-infected mothers following perinatal exposure to nucleoside analogues. AB - Clinical and biological observations of mitochondrial dysfunction in children exposed to zidovudine (azidothymidine, AZT) during the perinatal period rapidly followed similar observations in animal experiments. To date, two different disorders have been identified. The first, asymptomatic hyperlactatemia, is observed during treatment in one third of exposed newborns, and is reversible with treatment cessation. In rare cases, it is associated with symptomatic acidosis. Regression may be slow, taking up to several months after the end of the treatment. The long-term clinical consequences of this biochemical disturbance are unknown. The second disorder involves severe neurological symptoms, which become clinically detectable during the first 2 years of life. These symptoms are associated with a series of biochemical and ultrastructural changes consistent with persistent mitochondrial dysfunction. This latter phenomenon is rare, and affects only 0.3-0.5% of exposed children in the French pediatric cohort, in which observations continue. Despite initial controversy, several similar observations in other cohorts have since confirmed its occurrence. The pathophysiology of these two mitochondrial dysfunctions may differ. Continued efforts to identify and understand clinical mitochondrial toxicities are essential, given the intensification and diversification of perinatal prophylaxis strategies, and the number of pregnant women potentially involved. PMID- 17358032 TI - Elevated frequencies of micronucleated erythrocytes in infants exposed to zidovudine in utero and postpartum to prevent mother-to-child transmission of HIV. AB - Zidovudine-based antiretroviral therapies (ARTs) for treatment of HIV-infected pregnant women have markedly reduced mother-to-child transmission of the human immunodeficiency virus (HIV-1) from approximately 25% to <1%. However, zidovudine (ZDV; AZT), a nucleoside analogue, induces chromosomal damage, gene mutations, and cancer in animals following direct or transplacental exposure. To determine if chromosomal damage is induced by ZDV in infants exposed transplacentally, we evaluated micronucleated reticulocyte frequencies (%MN-RET) in 16 HIV-infected ART-treated mother-infant pairs. Thirteen women received prenatal ART containing ZDV; three received ART without ZDV. All infants received ZDV for 6 weeks postpartum. Venous blood was obtained from women at delivery and from infants at 1-3 days, 4-6 weeks, and 4-6 months of life; cord blood was collected immediately after delivery. Ten cord blood samples (controls) were obtained from infants of HIV-uninfected women who did not receive ART. %MN-RET was measured using a single laser 3-color flow cytometric system. Tenfold increases in %MN-RET were seen in women and infants who received ZDV-containing ART prenatally; no increases were detected in three women and infants who received prenatal ART without ZDV. Specifically, mean %MN-RET in cord blood of ZDV-exposed infants was 1.67 +/- 0.34 compared with 0.16 +/- 0.06 in non-ZDV ART-exposed infants (P = 0.006) and 0.12 +/- 0.02 in control cord bloods (P < 0.0001). %MN-RET in ZDV-exposed newborns decreased over the first 6 months of life to levels comparable to cord blood controls. These results demonstrate that transplacentalZDV exposure is genotoxic in humans. Long-term monitoring of HIV-uninfected ZDV-exposed infants is recommended to ensure their continued health. PMID- 17358033 TI - Mutagenicity of zidovudine, lamivudine, and abacavir following in vitro exposure of human lymphoblastoid cells or in utero exposure of CD-1 mice to single agents or drug combinations. AB - Experiments were performed to investigate the impact of zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using cell cloning assays for assessing the effects of individual drugs/drug combinations in (1) TK6 human lymphoblastoid cells exposed in vitro and (2) splenic lymphocytes from male CD-1 mice exposed transplacentally on days 12-18 of gestation. In TK6 cells, dose-related increases in HPRT and TK mutant frequencies were found following 3 days of exposure to AZT or 3TC alone (33, 100, or 300 microM), or to equimolar amounts of AZT-3TC. Compared with single drug exposures, AZT-3TC coexposures generally yielded enhanced elevations in HPRT and TK mutant frequencies. Mutagenicity experiments with ABC alone, or in combination with AZT-3TC, were complicated by the extreme cytotoxicity of ABC. Exposure of cells either to relatively high levels of AZT-3TC short-term (100 microM, 3 days), or to peak plasma-equivalent levels of AZT-3TC for an extended period (10 microM, 30 days), resulted in similar drug-induced mutagenic responses. Among sets of mice necropsied on days 13, 15, or 21 postpartum, Hprt mutant frequencies in T-cells were significantly elevated in the AZT-only (200 mg/kg bw/day) and AZT-3TC (200 mg AZT + 100 mg 3TC/kg bw/day) groups at 13 days of age. These results suggest that the mutagenicity by these nucleoside analogs is driven by cumulative dose, and raises the question of whether AZT-3TC has greater mutagenic effects than AZT alone in perinatally exposed children. PMID- 17358034 TI - 3'-azido-3'-deoxythymidine induces deletions in L5178Y mouse lymphoma cells. AB - 3'-Azido-3'-deoxythymidine (AZT), a nucleoside analogue used for the treatment of acquired immunodeficiency syndrome (AIDS), induced a significant dose-related increase in the thymidine kinase (Tk) mutant frequency (MF) in L5178Y/Tk(+/-) 3.7.2C mouse lymphoma cells. Treatment with 1 mg/ml (3,742 muM) AZT for 24 hr resulted in a MF of 407 x 10(-6) compared to a control MF of 84 x 10(-6). The MFs of the large and small colony mutants resulting from AZT exposure were 142 x 10( 6) and 265 x 10(-6), respectively. One hundred and fifty mutants from the 1 mg/ml (3,742 muM) AZT-treated culture and sixty-nine mutants from independent untreated cultures were isolated and analyzed. LOH analysis using a heteromorphic microsatellite locus located in the Tk gene was performed to determine the presence or absence of the Tk(+) allele. Eight other microsatellite markers spanning the entire mouse chromosome 11 also were examined for heterozygosity to determine the extent of LOH. In addition, Tk gene dosage analysis was conducted using Real-Time PCR in those mutants showing LOH at the Tk locus. The presence of only one Tk allele based on Real-Time PCR indicated that the mutant resulted from deletion while the presence of two alleles was consistent with a recombination event. More mutants from the AZT-treated culture showed Tk LOH than did independent mutants from the untreated cultures (91% vs. 64%) and the induced mutants also showed distinct chromosome 11 LOH patterns. The mutation spectrum of mutants from AZT-treated cells was also significantly different from that of spontaneous mutants. More deletions and fewer intragenic mutations were observed in the mutants from the AZT-treated culture than independent mutants from the untreated control. Our data indicate that AZT primarily induced LOH mutations in L5178Y mouse lymphoma cells and a large number of LOH mutations resulted from deletions. PMID- 17358035 TI - Expression of cartilage-related genes in bovine synovial tissue. AB - The synovium contains mesenchymal stem cells with chondrogenic potential. Although synovial and articular cartilage tissue develop from a common pool of mesenchymal cells, little is known about their genetic commonalities. In the present study, the mRNA levels for several cartilage-related proteins, namely, cartilage oligomeric matrix protein (COMP), Sox9, aggrecan, and collagen types I, II, IX, X, and XI, were measured using the real-time polymerase chain reaction. Our data reveal the synovium of calf metacarpal joints to physiologically express not only type I collagen but also COMP, Sox9, aggrecan, and collagen types X and XI. The mRNA levels for the latter five proteins lie between 2% and 15% of those in articular cartilage. We speculate that these genes are being expressed by chondroprogenitor cells, whose presence in the synovium reflects a common ontogenetic phase in the fetal development of this tissue and of articular cartilage. PMID- 17358036 TI - Refining teratogen warning symbols for diverse populations. AB - BACKGROUND: The current research reports on efforts to refine the design of recently developed teratogen warning symbols and to examine their interpretation by different populations such as those with low health literacy, adolescents, and individuals who are not fluent in English. METHODS: Alternative symbols identified as most successful in an earlier study were further refined through the use of multiple focus groups and expert review. Six symbols emerged as potential candidates to replace the current symbol. A nationally distributed field trial (n = 700) examined these six alternate teratogen warnings in addition to the symbol presently in use. RESULTS: Five of the alternate warning symbols exceeded the level of correct interpretation elicited by the current symbol. No symbol exceeded the ANSI limit of 5% critical confusion. Two symbols consistently elicited the most accurate responses in terms of message interpretation, target audience, intended action, and perceived consequences of ignoring the warning. CONCLUSIONS: This effort produced at least two viable alternative symbols that appear to be more effective than the current symbol at communicating both the instruction to not take while pregnant and the consequence that exposure could cause birth defects. Several results varied by participant characteristics. Understanding how members of diverse subpopulations might interact with these warnings should be informative to healthcare professionals. PMID- 17358037 TI - Risk for gastroschisis in primigravidity, length of sexual cohabitation, and change in paternity. AB - BACKGROUND: Maternal epidemiologic similarities between gastroschisis and preeclampsia have led to the objective of evaluating the risk for gastroschisis related to primigravidity, change in paternity, and length of cohabitation, considered as risk factors for preeclampsia. METHODS: The subjects were 288 newborns with isolated gastroschisis and 576 normal controls, matched by maternal age. They were ascertained in the Estudio Colaborativo Latino Americano de Malformaciones Congenitas hospital network of 10 South American countries between 1982 and 2005. Epidemiologic variables were compared among controls, between primigravidas and multigravidas, between multigravidas who had and had not changed partners, and between mothers with short and long cohabitation times with their partners. Risks associated with primigravidity, short cohabitation time, and changing paternity, as well as their combinations, were calculated. An eventual interaction between maternal age and the three risk factors was assessed. RESULTS: Only a short cohabitation time showed a significant OR for gastroschisis (OR = 2.36, 95% CI: 1.52-3.66, p < .001), whereas ORs were not significant for primigravidity (OR = 1.40, 95% CI: 0.84-2.35, p = .192) nor for changing paternity (OR = 1.20, 95% CI: 0.49-3.10, p = .752). The risk was highest for multigravidas who had changed partners (OR = 8.71, 95% CI: 2.93-21.12, p < .001), followed by multigravidas who had not changed partners (OR = 3.99, 95% CI: 1.07-15.43, p = .049), and by primigravidas (OR = 3.02, 95% CI: 1.58-5.76, p = .001), all having cohabitated for a short time. Maternal age did not modify these risks. CONCLUSIONS: Three groups at risk for a child with gastroschisis were identified, all having in common a short cohabitation time. Antigenic or "modern" lifestyle-related factors might be involved in the origin of gastroschisis. PMID- 17358038 TI - Symptom perception and functional morbidity across a 1-year follow-up in pediatric asthma. AB - The purpose of this study was to examine the association between asthma symptom perception measured during a 5-6 week baseline and functional morbidity measured prospectively across a 1-year follow-up. Symptom perception was measured by comparing subjective ratings with peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV(1)). We hypothesized that accurate symptom perception (ASP) would be associated with less functional morbidity. Participants consisted of 198 children with asthma ages 7-17 recruited from three sites. The children used a programmable electronic spirometer in the home setting to guess their PEFR prior to exhalation. Each "subjective" guess was classified as being in an ASP, dangerous symptom perception (DSP; underestimation of symptoms), or symptom magnification (SM; overestimation) zone based upon the corresponding measurement of PEFR or FEV(1). An index of functional morbidity was collected by parent report at baseline and across 1-year follow-up. A greater proportion of ASP blows and a lower proportion of DSP blows based on PEFR predicted less functional morbidity reported at baseline, independent of asthma severity and race/ethnicity. A greater proportion of ASP blows (using PEFR and FEV(1)) and a lower proportion of SM blows (using FEV(1)) predicted less functional morbidity across 1-year follow-up. Symptom perception was not associated with emergency department visits for asthma at baseline or across follow-up. In comparison to PEFR, FEV(1) more frequently detected a decline in pulmonary function that children did not report. Symptom perception measured in naturalistic settings was associated with functional morbidity at baseline and prospectively across 1-year follow-up. Support was found for including multiple measures of pulmonary function in the assessment of asthma symptom perception. PMID- 17358039 TI - Dual thyroid ectopia with a normally located pretracheal thyroid gland: case report and literature review. AB - BACKGROUND: Only 1 case with dual thyroid ectopy and a normally located thyroid gland has been reported. METHODS: We present the case of a 71-year-old woman who had 1-sided lateral neck swelling in the right submandibular space, which grew and doubled in size within 1 year. A CT scan demonstrated 2 right submandibular, lobulated, heterogeneously enhanced masses, an ectopic lingual thyroid, and bilateral thyroid goiter. A Tc-99m sodium pertechnetate thyroid scan revealed a cold area in the right lateral neck region below the submandibular gland, an ectopic lingual thyroid, and bilateral pretracheal thyroids. She underwent total thyroidectomy and en bloc excision of right neck masses. Thyroxin was prescribed following the surgery. RESULTS: Pathological diagnoses were ectopic thyroid tissue with goitrous change and bilateral thyroid goiter. CONCLUSION: This report demonstrates that dual ectopic thyroid tissue accompanying a normally located thyroid gland can exist and should be differentiated from head and neck malignancies. PMID- 17358040 TI - Measuring head and neck cancer symptom burden: the development and validation of the M. D. Anderson symptom inventory, head and neck module. AB - BACKGROUND: The aim of this study was to develop and validate a symptom inventory for patients with head and neck cancer and to assess the occurrence and severity of symptoms, the overall symptom burden, and the interference the symptoms cause in daily life. METHODS: Items were generated from a comprehensive literature review, our prior work, and focus groups with head and neck cancer patients, symptom researchers, and a multidisciplinary group of head and neck cancer health care workers. We selected 11 provisional head and neck cancer-specific items for addition to the core M. D. Anderson Symptom Inventory (MDASI), and conducted a cross-sectional validation study among patients with head and neck cancer. RESULTS: Construct validity was established using principal axis factoring with direct oblimin rotation, and tests of concurrent and known-groups validity were conducted. Two items were dropped because of low severity scores and low frequency of complaint, leaving 9 final head and neck cancer-specific items. The coefficient alpha reliabilities were 0.88, 0.83, and 0.92 for the 13 core MDASI items, the 9 head and neck cancer-specific items, and the 6 interference items, respectively. The most prevalent severe symptoms were problems with mucus, mouth/throat sores, tasting food, difficulty with chewing or swallowing, dry mouth, pain, and fatigue. CONCLUSIONS: The M. D. Anderson Symptom Inventory-Head and Neck (MDASI-HN) is a reliable and valid instrument to measure head and neck cancer symptom burden, and the interference symptoms cause in the major aspects of a patient's daily life. A subset of specifically distressing symptoms was identified, many of which are not included in commonly used head and neck cancer quality of life instruments. PMID- 17358041 TI - Pulmonary function and exercise testing in adult survivors of congenital diaphragmatic hernia. AB - Congenital diaphragmatic hernia (CDH) is accompanied by pulmonary hypoplasia and structural abnormalities of the pulmonary vascular bed. It is unknown whether pulmonary function, exercise capacity, and gas exchange during exercise are impaired in adult CDH survivors. The objective of this study was to assess the long-term pulmonary function, exercise capacity, and gas exchange during exercise and relate these findings with quality of life. Of the 23 patients eligible for this study, 12 adult CDH survivors (mean age, 24.3 +/- 4.1 years) with high-risk CDH agreed to participate. Pulmonary function tests, diffusion capacity, and a cardiopulmonary exercise test (CPET) were performed. The FEV1 (mean z-score +/- SD; -1.30 +/- 1.37), FEF25-75% (-1.49 +/- 1.14), and the KCO (-1.03 +/- 1.24) were found to be lower in CDH survivors. The RV/TLC ratio (28.2% +/- 5.0%) was found to be higher. Despite these abnormalities, percent predicted work load (102% +/- 17.2%) and percent predicted maximal oxygen uptake (90.8% +/- 18.9%) were normal in most of the patients. The quality of life of CDH survivors, assessed with the SF-36 questionnaire, is comparable to the general population. Comparison of participants to non-participants did not reveal significant differences in clinical characteristics. In this first study assessing pulmonary function in adult survivors of CDH, mild airway obstruction was observed in most of the patients together with a slightly reduced diffusion capacity for CO. Exercise capacity and gas exchange parameters were normal in this group, indicating that patients do not have a physical impairment, as reflected by a normal quality of life of CDH patients. PMID- 17358042 TI - Anti-inflammatory pharmacotherapy for wheezing in preschool children. AB - Accumulating evidence indicates that there are at least two phenotypes of wheezing in preschool years with distinct natural history. Frequent wheezing in the first 3 years of life with risk factors for asthma (e.g., eczema, maternal asthma) predicts symptoms in older age, while infrequent viral-associated wheezing without risk factors for asthma has a benign prognosis. This systematic review summarizes evidence on the use of anti-inflammatory medications in preschool children with wheezing. Literature search was performed using Medline and the Cochrane Library. Retrieved articles were critically appraised. Episodic use of high-dose inhaled corticosteroids (>1,600 mcg/day of beclomethasone) may ameliorate severity of intermittent viral-associated wheezing. Maintenance inhaled corticosteroids can control symptoms in children with frequent wheezing associated with risk factors for asthma. Inhaled corticosteroids do not alter the natural history of wheezing even when started early in life and could have a negative impact on linear growth rate. Short courses of oral corticosteroids have been proposed as an effective measure to control exacerbations of symptoms although there is little evidence supporting their use. Some studies support the administration of non-steroidal anti-inflammatory medications (leukotriene pathway modifiers, cromones, methylxanthines) for mild frequent wheezing. Maintenance inhaled corticosteroids is the most effective measure for controlling frequent wheezing in preschool children, especially when accompanied by risk factors for asthma. This treatment does not affect the natural history of wheezing, although deceleration of linear growth rate is the most commonly recognized systemic adverse effect. PMID- 17358043 TI - Reduced toll-like receptor 4 and substance P gene expression is associated with airway bacterial colonization in children. AB - Neuro-immune interactions are increasingly relevant to human health and disease. The neuropeptide Substance P also has antibacterial activity and bears similarities to the innate immune antibacterial defensins. This suggests possible co-regulation of neuropeptide and innate immune mediators. In this study, non bronchoscopic bronchoalveolar lavage (BAL) was performed on 69 children. BAL was examined for cellular profile, microbiology (bacteria, virus) and gene expression for TLRs 2, 3, 4; chemokine receptors (CCR3, CCR5, CXCR1); neurotrophins and neurokinin genes (TAC1, TAC3, CGRP, NGF). In children with bacterial colonization (n=10) there was an airway inflammatory response with increased BAL neutrophils, IL-8 protein, and CXCR1 expression. Substance P (TAC1) and TLR4 RNA expression were reduced in children with bacterial colonization. TLR3 mRNA was increased in 7.2% (n=5) children with rhinovirus, and there was a non-significant trend to increased TLR2. There is evidence for co-regulation of neurokinin (TAC1) and TLR4 gene expression in airway cells from children with airway bacterial colonization and their reduced expression may be associated with an impaired bacterial clearance. PMID- 17358044 TI - Synthesis and in vitro characterization of an ABC triblock copolymer for siRNA delivery. AB - The ability to specifically down-regulate gene expression using the RNAi pathway in mammalian cells has tremendous potential in therapy and in basic science. However, delivery systems capable of efficient and biocompatible delivery of siRNA to target cells are not yet satisfactory. Here, we report the synthesis and in vitro characterization of ABC triblock copolymers that self-assemble with siRNA based on electrostatics and with each other by hydrophobic interactions. The ABC triblock copolymer is based on poly(ethylene glycol) (PEG), poly(propylene sulfide) (PPS), and a positively charged peptide (PEG-PPS peptide). The diblock copolymer PEG(45)-PPS(5,10) was synthesized using anionic polymerization of propylene sulfide upon a PEG macroinitiator, and the peptide domain was coupled to the PPS terminus using a disulfide exchange reaction with an N-terminal cysteine residue on the peptide. The peptides were designed to interact electrostatically with siRNA, selecting the TAT peptide domain of HIV (RKKRRQRRR) and an oligolysine (Lys(9)). The resulting triblock copolymers were able to self-assemble with siRNA as demonstrated by dynamic light scattering and gel electrophoresis. Complex size was found to be dependent on the amount of polymer used (charge ratio) and the length of the hydrophobic PPS block, achieving sizes ranging from 171 nm to 601 nm. Cell internalization and gene expression down-regulation studies showed that the triblock copolymers are able to transport siRNA inside the cell and mediate gene expression down-regulation, with the amount of internalization and gene transfer affected by charge ratio, PPS length, and the presence of serum. The proposed triblock was able to mediate gene expression down-regulation of GAPDH, achieving up to 90.5% +/- 0.02% down regulation. PMID- 17358045 TI - Fully packed capillary electrochromatographic microchip with self-assembly colloidal silica beads. AB - A fully packed capillary electrochromatographic (CEC) microchip showing improved solution and chip handling was developed. Microchannels for the CEC microchip were patterned on a cyclic olefin copolymer substrate by injection molding and packed fully with 0.8-microm monodisperse colloidal silica beads utilizing a self assembly packing technique. The silica packed chip substrate was covered and thermally press-bonded. After fabrication, the chip was filled with buffer solution by self-priming capillary action. The self-assembly packing at each channel served as a built-in nanofilter allowing quick loading of samples and running buffer solution without filtration. Because of a large surface area-to volume ratio of the silica packing, reproducible control of electroosmotic flow was possible without leveling of the solutions in the reservoirs resulting 1.3% rsd in migration rate. The capillary electrophoretic separation characteristics of the chip were studied using fluorescein isothiocyanate (FITC)-derivatized amino acids as probe molecules. A mixture of FITC and four FITC-derivatized amino acids was successfully separated with 2-mm separation channel length. PMID- 17358046 TI - Capacitive detection in ultrathin chemosensors prepared by molecularly imprinted grafting photopolymerization. AB - The usual applications of capacitive detection in chemo- and biosensors are based on changes in effective thickness of insulating layers due to adsorption of analyte onto receptors. Ultrathin chemosensors based on molecularly imprinted polymerization enable a realization of another capacitive approach that exploits changes in electrical capacitance due to modification of the dielectric constant of the polymer. Such chemosensors were prepared by photografted molecularly imprinted polymerization on the surface of gold electrodes. An adsorbed layer of hydrophobic photoinitiator (benzophenone) provided grafted polymerization on the surface of the alkanethiol-modified gold electrode. The chemosensors were characterized by cyclic voltammetry, impedance spectroscopy, and scanning electron and atomic force microscopy. Binding of analyte was detected by measurements of electrical capacitance. The results indicate a decrease of the dielectric constant of the polymer layer due to analyte binding up to 20%. PMID- 17358047 TI - Delta conversion parameter between pH scales (SWpH and SSpH) in acetonitrile/water mixtures at various compositions and temperatures. AB - The SSpH in acetonitrile/water mixtures at different temperatures cannot be directly measured because of the lack of calibration buffers in these hydroorganic media at most temperatures different from 25 degrees C. In this paper, the delta parameter has been determined for acetonitrile/water mixtures from 0 up to 90% acetonitrile at different temperatures from 15 to 60 degrees C, and the values were fitted to a very simple simultaneous function of composition and temperature. The delta values allow conversion of the SWpH scale (pH measured in acetonitrile/water with electrodes calibrated in water) to the SSpH scale (pH measured in acetonitrile/water with electrodes calibrated in the same acetonitrile/water mixture). The practical determination of SWpH is direct because the calibration of the electrodes is carried out with commercial aqueous standard buffers. Thus, the SSpH value of any buffered acetonitrile/water mobile phase used in reversed-phase liquid chromatography, which is directly related to the ionized fraction of analyte and, therefore, to its average retention, can be easily known at any temperature from the measured SWpH and the corresponding delta value. PMID- 17358048 TI - Solution structure of the PABC domain from wheat poly (A)-binding protein: an insight into RNA metabolic and translational control in plants. AB - In animals, the PABC domain from poly (A)-binding protein recruits proteins containing a specific interacting motif (PAM-2) to the mRNP complex. These proteins include Paip1, Paip2, and eukaryotic release factor 3 (eRF3), all of which regulate PABP function in translation. The following reports the solution structure of PABC from Triticum avestium (wheat) poly (A)-binding protein determined by NMR spectroscopy. Wheat PABC (wPABC) is an alpha-helical protein domain, which displays a fold highly similar to the human PABC domain and contains a PAM-2 peptide binding site. Through a bioinformatics search, several plant proteins containing a PAM-2 site were identified including the early response to dehydration protein (ERD-15), which was previously shown to regulate PABP-dependent translation. The plant PAM-2 proteins contain a variety of conserved sequences including a PABP-interacting 1 motif (PAM-1), RNA binding domains, an SMR endonuclease domain, and a poly (A)-nuclease regulatory domain, all of which suggest a function in either translation or mRNA metabolism. The proteins identified are well conserved throughout plant species but have no sequence homologues in metazoans. We show that wPABC binds to the plant PAM-2 motif with high affinity through a conserved mechanism. Overall, our results suggest that plant species have evolved a distinct regulatory mechanism involving novel PABP binding partners. PMID- 17358049 TI - A novel four-amino acid determinant defines conformational freedom within chorionic gonadotropin beta-subunits. AB - On the basis of apparent molecular mass heterogeneity following reducing versus nonreducing SDS-PAGE, we determined that the beta-subunit of macaque (Macaca fascicularis) chorionic gonadotropin (mCG-beta) is more conformationally constrained than the beta-subunit of human chorionic gonadotropin (hCG-beta). The amino acid sequences of these two subunits are 81% identical. To determine the conformational variance source, which was not due to glycosylation differences, we generated a series of hCG-beta-mCG-beta chimeras and identified domains that contributed to CG-beta conformational freedom. We discovered that the CG-beta 54 101 domain contained a small subdomain, residues 74-77, that regulated the conformational freedom of the beta-subunit; i.e., when residues 74-77 were of macaque origin (PGVD), the mutated hCG-beta subunit displayed macaque-like conformational rigidity, and when residues 74-77 were of human origin (RGVN), the mutated mCG-beta subunit displayed human-like conformational freedom and microheterogeneity. Additionally, CG-beta N-terminal domain residues (8, 18, 42, and 46-48) were also found to influence CG-beta conformational freedom when residues 74-77 were of human but not macaque origin. The biological significance of the CG-beta conformational variance was tested using a biological assay that showed that the hCG-alpha-hCG-beta heterodimer facilitated human CG receptor mediated cAMP-driven luciferase reporter gene activity in HEK cells nearly 1 order of magnitude more effectively than the hCG-alpha-mCG-beta chimera. Together, these data demonstrate that two essential amino acid residues within a four-amino acid subdomain regulated CG-beta conformational freedom and that a conformational difference between hCG-beta and mCG-beta was recapitulated in the context of receptor-mediated CG heterodimer signal transduction activation. PMID- 17358050 TI - Sterol and pH interdependence in the binding, oligomerization, and pore formation of Listeriolysin O. AB - Listeriolysin O (LLO) is the most important virulence factor of the intracellular pathogen Listeria monocytogenes. Its main task is to enable escape of bacteria from the phagosomal vacuole into the cytoplasm. LLO belongs to the cholesterol dependent cytolysin (CDC) family but differs from other members, as it exhibits optimal activity at low pH. Its pore forming ability at higher pH values has been largely disregarded in Listeria pathogenesis. Here we show that high cholesterol concentrations in the membrane restore the low activity of LLO at high pH values. LLO binds to lipid membranes, at physiological or even slightly basic pH values, in a cholesterol-dependent fashion. Binding, insertion into lipid monolayers, and permeabilization of calcein-loaded liposomes are maximal above approximately 35 mol % cholesterol, a concentration range typically found in lipid rafts. The narrow transition region of cholesterol concentration separating low and high activity indicates that cholesterol not only allows the binding of LLO to membranes but also affects other steps in pore formation. We were able to detect some of these by surface plasmon resonance-based assays. In particular, we show that LLO recognition of cholesterol is determined by the most exposed 3beta hydroxy group of cholesterol. In addition, LLO binds and permeabilizes J774 cells and human erythrocytes in a cholesterol-dependent fashion at physiological or slightly basic pH values. The results clearly show that LLO activity at physiological pH cannot be neglected and that its action at sites distal to cell entry may have important physiological consequences for Listeria pathogenesis. PMID- 17358051 TI - Synthesis of a new class of druglike angiotensin II C-terminal mimics with affinity for the AT2 receptor. AB - Four tripeptides corresponding to the C-terminal region of angiotensin II were synthesized. One of these peptides (Ac-His-Pro-Ile) showed moderate binding affinity for the AT2 receptor. Two aromatic histidine-related scaffolds were synthesized and introduced in the tripeptides to give eight new peptidomimetic structures. Three of the new peptide-derived druglike molecules exhibited selective, nanomolar affinity for the AT2 receptor. These ligands may become lead compounds in the future development of novel classes of selective AT2 receptor agonists. PMID- 17358052 TI - Analogues of acifran: agonists of the high and low affinity niacin receptors, GPR109a and GPR109b. AB - Recently identified GPCRs, GPR109a and GPR109b, the high and low affinity receptors for niacin, may represent good targets for the development of HDL elevating drugs for the treatment of atherosclerosis. Acifran, an agonist of both receptors, has been tested in human subjects, yet until recently very few analogs had been reported. We describe a series of acifran analogs prepared using newly developed synthetic pathways and evaluated as agonists for GPR109a and GPR109b, resulting in identification of compounds with improved activity at these receptors. PMID- 17358053 TI - Syntheses and characterization of six coordination polymers of zinc(II) and cobalt(II) with 1,3,5-benzenetricarboxylate anion and bis(imidazole) ligands. AB - Six new coordination polymers, namely [Zn1.5(BTC)(L1)(H2O)2].1.5H2O (1), [Zn3(BTC)2(L2)3] (2), [Zn3(BTC)2(L3)1.5(H2O)].H2O (3), [Co6(BTC)4(L1)6(H2O)3].9H2O (4), [Co1.5(BTC)(L2)1.5].0.25H2O (5), and [Co4(BTC)2(L3)2(OH)2(H2O)].4.5H2O (6), where L1 = 1,2-bis(imidazol-1 ylmethyl)benzene, L2 = 1,3-bis(imidazol-1-ylmethyl)benzene, L3 = 1,1'-(1,4 butanediyl)bis(imidazole), and BTC = 1,3,5-benzenetricarboxylate anion, were synthesized under hydrothermal conditions. In 1-6, each of L1-L3 serves as a bidentate bridging ligand. In 1, BTC anions act as tridentate ligands, and compound 1 shows a 2D polymeric structure which consists of 2-fold interpenetrating (6, 3) networks. In compound 2, BTC anions coordinate to zinc cations as tridentate ligands to form a net with (64.82)2(86)(62.8)2 topology. In compound 3, BTC anions act as tetradentate ligands and coordinate to zinc cations to form a net with (4.62.83)2(8.102)(4.6.83.10)2 topology. In compound 5, each BTC anion coordinates to three Co cations, and the framework of 5 can be simplified as (64.82)2(62.82.102)(63)2 topology. For 4 and 6, the 2D cobalt-BTC layers are linked by bis(imidazole) ligands to form 3D frameworks. In 6, the Co centers are connected by micro3-OH and carboxylate O atoms to form two kinds of cobalt-oxygen clusters. Thermogravimetric analyses (TGA) for these compounds are discussed. The luminescent properties for 1-3 and magnetic properties for 4-6 are also discussed in detail. PMID- 17358054 TI - Self-assembly reactions between the cis-protected metal corners (N-N)MII (N-N = ethylenediamine, 4,4'-substituted 2,2'-bipyridine; M = Pd, Pt) and the fluorinated edge 1,4-bis(4-pyridyl)tetrafluorobenzene. AB - The self-assembly reactions between the fluorinated ditopic ligand 1,4-bis(4 pyridyl)tetrafluorobenzene (A) and different nitrogen-protected palladium(II) and platinum(II) complexes have been investigated. While dynamic equilibria between molecular triangles and squares were observed when the diimine compounds 4,4' R2bipy (bipy = 2,2'-bipyridine; R = H, Me, t-Bu) were employed as ancillary ligands, only square species were obtained from ethylenediamine (en) derivatives. Characterization of the obtained metallomacrocycles was accomplished by 1H and 19F NMR spectroscopy in combination with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR). Molecular dynamics simulations (UFF) have been performed to interpret the influence of the fluorinated ring on the square/triangle relative stability. Density functional calculations using the GIAO method have been employed for the interpretation of the chemical shift assignments. The study of the ability of these compounds to act as hosts of electron-rich aromatic guests has shown that the palladium ethylenediamine square is capable of establishing this type of intermolecular interaction exclusively in aqueous media. The host-guest stoichiometry and association constants have been determinated by 1H NMR spectroscopy. PMID- 17358055 TI - Preparation and isolation of dithiolene thiophosphoryl molecules as stable, protected forms of dithiolene ligands. AB - The reaction of P4S10 with acyloins, RC(O)CH(OH)R, in refluxing dioxane, followed by the addition of alkylating agents, forms dithiolene thiophosphoryl thiolate compounds, (R2C2S2)P(S)(SR'), which are readily isolated and purified. The compounds that have been prepared and identified spectroscopically are those with R = p-anisyl, R' = Me (1); R = p-anisyl, R' = Bz (2); R = Ph, R' = Me (4); R = Et, R' = Bz (5). Compounds 1, 2, and 4 were structurally characterized by X-ray crystallography and found to possess a tetrahedral coordination geometry about the phosphorus atom, with overall Cs symmetry. In each case, the mirror plane bisects the dithiolene S-P-S chelate and contains the thiophosphoryl bond, which ranges in length from 1.9241(8) to 1.9361(7) A. The use of 2 (bromomethyl)naphthalene as organic electrophile in the P4S10/acyloin reaction produced bis(2-methylnaphthalenyl) disulfide as the only identifiable product. The substitution of Lawesson's reagent for P4S10 in reactions with acyloins produced deoxy acyloin rather than products resulting from chalcogen exchange. Compounds 1-2 and 4-5 are Group 5 analogues of 1,3-dithiol-2-ones, (R2C2S2)C=O, and undergo a similar hydrolysis in aqueous base to liberate ene-1,2-dithiolate dianions from which corresponding metal dithiolene complexes may be prepared. Deprotection of 1 in MeO-/MeOH, followed by the addition of NiCl2.6H2O and then I2, produces square planar [Ni(S2C2(C6H4-p-OCH3)2)2] (8) in 93% yield. A high resolution structure of 8 (P) reveals dithiolene C-C and C-S bond lengths that are clearly indicative of the thionyl radical monoanionic nature of the ligand. The use of isolated (R2C2S2)P(S)(SR') compounds as a dithiolene ligand source for the preparation of metal dithiolene complexes offers the advantages of clean reactivity and high yield. PMID- 17358056 TI - The structures and electronic configuration of compound I intermediates of Helicobacter pylori and Penicillium vitale catalases determined by X-ray crystallography and QM/MM density functional theory calculations. AB - The structures of Helicobacter pylori (HPC) and Penicillium vitale (PVC) catalases, each with two subunits in the crystal asymmetric unit, oxidized with peroxoacetic acid are reported at 1.8 and 1.7 A resolution, respectively. Despite the similar oxidation conditions employed, the iron-oxygen coordination length is 1.72 A for PVC, close to what is expected for a Fe=O double bond, and 1.80 and 1.85 A for HPC, suggestive of a Fe-O single bond. The structure and electronic configuration of the oxoferryl heme and immediate protein environment is investigated further by QM/MM density functional theory calculations. Four different active site electronic configurations are considered, Por*+-FeIV=O, Por*+-FeIV=O...HisH+, Por*+-FeIV-OH+ and Por-FeIV-OH (a protein radical is assumed in the latter configuration). The electronic structure of the primary oxidized species, Por*+-FeIV=O, differs qualitatively between HPC and PVC with an A2u-like porphyrin radical delocalized on the porphyrin in HPC and a mixed A1u like "fluctuating" radical partially delocalized over the essential distal histidine, the porphyrin, and, to a lesser extent, the proximal tyrosine residue. This difference is rationalized in terms of HPC containing heme b and PVC containing heme d. It is concluded that compound I of PVC contains an oxoferryl Por*+-FeIV=O species with partial protonation of the distal histidine and compound I of HPC contains a hydroxoferryl Por-FeIV-OH with the second oxidation equivalent delocalized as a protein radical. The findings support the idea that there is a relation between radical migration to the protein and protonation of the oxoferryl bond in catalase. PMID- 17358057 TI - Protein phosphorylation and intermolecular electron transfer: a joint experimental and computational study of a hormone biosynthesis pathway. AB - Protein phosphorylation is a common regulator of enzyme activity. Chemical modification of a protein surface, including phosphorylation, could alter the function of biological electron-transfer reactions. However, the sensitivity of intermolecular electron-transfer kinetics to post-translational protein modifications has not been widely investigated. We have therefore combined experimental and computational studies to assess the potential role of phosphorylation in electron-transfer reactions. We investigated the steroid hydroxylating system from bovine adrenal glands, which consists of adrenodoxin (Adx), adrenodoxin reductase (AdR), and a cytochrome P450, CYP11A1. We focused on the phosphorylation of Adx at Thr-71, since this residue is located in the acidic interaction domain of Adx, and a recent study has demonstrated that this residue is phosphorylated by casein kinase 2 (CK2) in vitro.1 Optical biosensor experiments indicate that the presence of this phosphorylation slightly increases the binding affinity of oxidized Adx with CYP11A1ox but not AdRox. This tendency was confirmed by KA values extracted from Adx concentration-dependent stopped flow experiments that characterize the interaction between AdRred and Adxox or between Adxred and CYP11A1ox. In addition, acceleration of the electron-transfer kinetics measured with stopped-flow is seen only for the phosphorylated Adx CYP11A1 reaction. Biphasic reaction kinetics are observed only when Adx is phosphorylated at Thr-71, and the Brownian dynamics (BD) simulations suggest that this phosphorylation may enhance the formation of a secondary Adx-CYP11A1 binding complex that provides an additional electron-transfer pathway with enhanced coupling. PMID- 17358058 TI - Core/shell quantum dots with high relaxivity and photoluminescence for multimodality imaging. AB - A series of core/shell CdSe/Zn1-xMnxS nanoparticles were synthesized for use in dual-mode optical and magnetic resonance (MR) imaging techniques. Mn2+ content was in the range of 0.6-6.2% and varies with the thickness of the shell or amount of Mn2+ introduced to the reaction. These materials showed high quantum yield (QY), reaching 60% in organic solvent. Water-soluble nanoparticles were obtained by capping the core/shell particles with amphiphilic polymer, and the QY values in water reached 21%. These materials also demonstrated high relaxivity with r1 values in the range of 11-18 mM-1 s-1 (at room temperature, 7 T). Both optical and MR imaging were performed on nanoparticles in aqueous solution and applied to cells in culture. The results showed that the QY and manganese concentration in the particles was sufficient to produce contrast for both modalities at relatively low concentrations of nanoparticles. PMID- 17358059 TI - Aromatic substitution with hypercloso C(BCH3)11: a new mechanism. PMID- 17358060 TI - Engineering hydrogen-bonded molecular crystals built from derivatives of hexaphenylbenzene and related compounds. AB - Hexakis[4-(2,4-diamino-1,3,5-triazin-6-yl)phenyl]benzene (4) incorporates a disc shaped hexaphenylbenzene core and six peripheral diaminotriazine groups that can engage in hydrogen bonding according to established motifs. Under all conditions examined, compound 4 crystallizes as planned to give closely related noninterpenetrated three-dimensional networks built from sheets in which each molecule has six hydrogen-bonded neighbors. In the structure of compound 4, the number of hydrogen bonds per molecule and the percentage of volume accessible to guests approach the highest values so far observed in molecular networks. Analogue 5 (which has the same hexaphenylbenzene core but only four diaminotriazine groups at the 1,2,4,5-positions) and analogue 7 (in which the two unsubstituted phenyl groups of compound 5 are replaced by methyl groups) crystallize according to a closely similar pattern. Analogues with flatter pentaphenylbenzene or tetraphenylbenzene cores crystallize differently, underscoring the importance of maintaining a consistent molecular shape in attempts to engineer crystals with predetermined properties. PMID- 17358061 TI - Influence of defects on the electrical characteristics of mercury-drop junctions: self-assembled monolayers of n-alkanethiolates on rough and smooth silver. AB - This paper compares the structural and electrical characteristics of self assembled monolayers (SAMs) of n-alkanethiolates, SCn (n = 10, 12, 14), on two types of silver substrates: one used as-deposited (AS-DEP) by an electron-beam evaporator, and one prepared using the method of template-stripping. Atomic force microscopy showed that the template-stripped (TS) silver surfaces were smoother and had larger grains than the AS-DEP surfaces, and reflectance-absorbance infrared spectroscopy showed that SAMs formed on TS substrates were more crystalline than SAMs formed on AS-DEP substrates. The range of current densities, J (A/cm2), measured through mercury-drop junctions incorporating a given SAM on AS-DEP silver was, on average, several orders of magnitude larger than the range of J measured through the same SAM on TS silver, and the AS-DEP junctions failed, on average, 3.5 times more often within five current density voltage (J-V) scans than did TS junctions (depending on the length of the alkyl chains of the molecules in the SAM). The apparent log-normal distribution of J through the TS junctions suggests that, in these cases, it is the variability in the effective thickness of the insulating layer (the distance the electron travels between electrodes) that results in the uncertainty in J. The parameter describing the decay of current density with the thickness of the insulating layer, beta, was either 0.57 A-1 at V = +0.5 V (calculated using the log-mean of the distribution of values of J) or 0.64 A-1 (calculated using the peak of the distribution of values of J) for the TS junctions; the latter is probably the more accurate. The mechanisms of failure of the junctions, and the degree and sources of uncertainty in current density, are discussed with respect to a variety of defects that occur within Hg-drop junctions incorporating SAMs on silver. PMID- 17358062 TI - Chiral Bronsted acid-catalyzed direct asymmetric Mannich reaction. PMID- 17358063 TI - Secondary deuterium isotope effects on the acidity of carboxylic acids and phenols. AB - Secondary deuterium isotope effects (IEs) on acidities have been accurately measured by an NMR titration method applicable to a mixture of isotopologues. Deuteration definitely decreases the acidity of carboxylic acids and phenols, by up to 0.031 in the DeltapK per D. For aliphatic acids, the IEs decrease as the site of deuteration becomes more distant from the OH, as expected, but a surprising result is that IEs in both phenol and benzoic acid do not decrease as the site of deuteration moves from ortho to meta to para. The experimental data are supported by ab initio computations, which, however, substantially overestimate the IEs. The discrepancy does not seem to be due to solvation. The IEs originate in isotope-sensitive vibrations whose frequencies and zero-point energies are lowered upon deprotonation. In the simplest case, formate, the key vibration can be recognized as the C-H stretch, which is weakened by delocalization of the oxygen lone pairs. For the aromatic acids, delocalization cannot account for the near constancy of IEs from ortho, meta, and para deuteriums, but the observed IEs are consistent with calculated vibrational frequencies and electron densities. Moreover, the ability of the frequency analysis to account for the IEs is evidence against an inductive origin. PMID- 17358064 TI - Gold-catalyzed deoxygenated cyclization of cis-2,4-dien-1-als with regioselective addition of two nucleophiles. One-pot synthesis of highly functionalized cyclopentene framework. PMID- 17358065 TI - UV-driven reversible switching of a roselike vanadium oxide film between superhydrophobicity and superhydrophilicity. PMID- 17358066 TI - Total synthesis of 2'-O-methylmyxalamide D and (6E)-2'-O-methylmyxalamide D. PMID- 17358067 TI - Kinetic resolution of hydroperoxides with enantiopure phosphines: preparation of enantioenriched tertiary hydroperoxides. PMID- 17358068 TI - Layered copper metagermanate nanobelts: hydrothermal synthesis, structure, and magnetic properties. PMID- 17358069 TI - Protease-triggered dispersion of nanoparticle assemblies. PMID- 17358070 TI - Cobalt-catalyzed diastereoselective reductive [3 + 2] cycloaddition of allenes and enones. PMID- 17358071 TI - Cascade approach toward the core structure of neosarpagine. AB - [reaction: see text] A palladium-catalyzed domino sequence was developed to rapidly construct the core structure of neosarpagine and other quinuclidine related alkaloids. The cyclization of ketone 11 to ethylidene 4 with Pd(dba)2, DPEphos, LiHMDS, and ZnCl2 in THF represents a new domino process wherein a nonstabilized enolate served as a nucleophile. PMID- 17358072 TI - Synthesis of beta-C-galacto-pyranosides with fluorine on the pseudoanomeric substituent. AB - [reaction: see text] beta-C-galacto-Pyranosides with CHF and CF2 substitutes for the glycosidic oxygen were prepared through a four-step sequence starting from a central 1-thio-1,2-O-isopropylidene acetal alcohol and different alpha-fluoro- and alpha,alpha-difluoro acids. The key step in the synthesis is the oxocarbenium cyclization of an intermediate enol ether-thioacetal to a C1-substituted glycal. PMID- 17358073 TI - Palladium-catalyzed arylation of electron-rich heterocycles with aryl chlorides. AB - [reaction: see text] Palladium-catalyzed C-H activation: cheap aryl chlorides can now be used for the arylation of a wide variety of electron-rich heterocycles. The key to the success of this reaction is the use of a bulky, electron-rich phosphine ligand. No copper additives are needed. PMID- 17358074 TI - Synthesis of carbamates and ureas using Zr(IV)-catalyzed exchange processes. AB - [reaction: see text] Zirconium(IV)-catalyzed exchange processes have been developed to prepare both carbamates and ureas from dialkyl carbonates and carbamates employing 2-hydroxypyridine (HYP) and 4-methyl-2-hydroxyquinoline (MeHYQ) as catalytic additives, respectively. A microwave acceleration effect was observed in Zr(IV)-catalyzed carbamate-urea exchange. PMID- 17358075 TI - Highly beta-selective O-glucosidation due to the restricted twist-boat conformation. AB - [reaction: see text] Ethyl 1-thio-2,3,4,6-tetrakis-O-triisopropylsilyl-beta-d glucopyranoside, ethyl 6-O-benzyl-1-thio-2,3,4-tris-O-triisopropylsilyl-beta-d glucopyranoside, and ethyl 6-O-pivaloyl-1-thio-2,3,4-tris-O-triisopropylsilyl beta-d-glucopyranoside induced highly beta-selective O-glucosidations. Among them, the 6-O-pivaloylated substrate provided the best selectivity up to alpha/beta = 3:97 with cyclohexylmethanol, and the substrate was used for glucosidations with secondary and tertiary alcohols in a highly beta-selective manner. The selectivity would be caused by the twist-boat conformation of the pyranose; this is the first beta-selective O-glucosidation based on conformational control of the pyranose ring. PMID- 17358076 TI - Rheological characterization of in situ crosslinkable hydrogels formulated from oxidized dextran and N-carboxyethyl chitosan. AB - The gelation kinetics of an in situ gelable hydrogel formulated from oxidized dextran (Odex) and N-carboxyethyl chitosan (CEC) was investigated rheologically. Both Schiff base mediated chemical and physical crosslinking account for its rapid gelation (30-600 s) between 5 and 37 degrees C. The correlation between gelation kinetics and hydrogel properties with Odex/CEC concentration, their feed ratio, and temperature were elucidated. The gelation time determined from crossing over of storage moduli (G') and loss moduli (G' ') was in good agreement with that deduced from frequency sweeping tests according to the Winter-Chambon power law. The power law exponents for a 2% (w/v) Odex/CEC solution (ratio 5:5) at the gel point was 0.61, which is in excellent agreement with the value predicted from percolation theory (2/3). Temperature dependence of gelation time for the same hydrogel formulation is well-described by an Arrhenius plot with its apparent activation energy calculated at 51.9 kJ/mol. PMID- 17358077 TI - Protection of oligonucleotides against enzymatic degradation by pegylated and nonpegylated branched polyethyleneimine. AB - Among the cationic polymers, polyethyleneimine (PEI) is a promising candidate for delivery of oligodeoxynucleotides (ODNs). In this study, we wondered whether pegylation of PEI influences the complexation with ODNs. We especially aimed to investigate whether ODNs are differently protected against enzymatic degradation in PEI and polyethylene glycol-polyethyleneimine (PEG-PEI) polyplexes. Using fluorescence resonance energy transfer combined with fluorescence correlation spectroscopy, we found that PEI/ODN polyplexes remain to protect the ODNs they carry over a prolonged period of time while in PEG-PEI/ODN polyplexes the degradation of the ODNs slowly proceeds. We attribute this to the fact that PEI seems to compact the ODNs more firmly in the polyplexes' core than PEG-PEI, which apparently also results in a better protection against enzymatic degradation. These observations may also influence the efficiency of PEI-based ODN delivery in vivo, where pegylation is an attractive strategy to enhance the stability of the polyplexes in the blood stream. PMID- 17358078 TI - Aggregation of alkyllithiums in tetrahydrofuran. AB - Density functional theory was used to examine the solvation number and aggregation state of several alkyllithium compounds in clusters with tetrahydrofuran molecules coordinated to each lithium atom. We then made the microsolvation approximation and approximated the bulk free energy of solvation by the free energy of clustering with solvent molecules in the gas phase. The trends in the computed results are in reasonable agreement with the available experimental data. PMID- 17358079 TI - Subphthalocyanine-fused dimers and trimers: synthetic, electrochemical, and theoretical studies. AB - Subphthalocyanine (SubPc)-fused dimers and trimers bearing fluorine, iodine, and thioether peripheral substituents were synthesized and characterized. Absorption spectroscopy and electrochemical studies revealed (i) that the substituents have a strong effect on the electronic properties of the macrocycles and (ii) that there is good communication between the subphthalocyaninic moieties within the oligomeric structures. Theoretical calculations at DFT/6-31G(d,p) computational level and electron density studies support the experimental findings. The frontier orbitals in the dimers and trimers were also shown to be significantly altered with respect to those of SubPcs as a consequence of the extension of the conjugation associated with symmetry breaking. Time-dependent density functional theory calculations reproduced the differences observed in the UV-vis spectra of the fused dimers and the monomeric SubPcs. PMID- 17358080 TI - Generation and reactions of Pentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]non-4-ene. AB - The highly pyramidalized alkene, pentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]non-4-ene (9), has been generated via treatment of 4,5 diiodopentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]nonane (12) with n-butyllithium and tert-butyllithium. The title alkene has also been trapped as its Diels-Alder adduct with 1,3-diphenylisobenzofuran, 2,5-dimethylfuran, and spiro[2.4]hepta-4,6 diene. Products resulting from alkyllithium addition to the pyramidalized double bond of 9 have been isolated and fully characterized spectroscopically. The geometry, olefin strain energy, heat of hydrogenation, and relative HOMO/LUMO energies of 9 have been obtained by ab initio calculations at the MP2 and B3LYP levels using the 6-31G* basis set. PMID- 17358081 TI - Complexation of triptycene-based cylindrical macrotricyclic polyether toward diquaternary salts: ion-controlled binding and release of the guests. AB - Triptycene-based cylindrical macrotricyclic polyether 1 has been proved to be an efficient host for the complexation with diquaternary salts in solution and in the solid state. Moreover, it was also found that binding and release of the guest molecules could be easily controlled by the addition and removal of potassium ions. PMID- 17358083 TI - Solid-phase preparation of a pilot library derived from the 2,3,4,5-tetrahydro-1H benzo[b]azepin-5-amine scaffold. AB - A convenient and reliable solid-phase strategy for the synthesis of di- and trisubstituted benzazepine derivatives was developed. 5-Amino-1-tert butoxycarbonyl-2,3,4,5-tetrahydro-1H-benzo[b]azepine and 5-amino-1-tert butoxycarbonyl-7-bromo-2,3,4,5-tetrahydro-1H-benzo[b]azepine G-protein coupled receptor-targeted (GPCR-targeted) scaffolds were efficiently synthesized in a six step solution-phase process, immobilized on the acid-labile FMPB-AM resin, and further functionalized through acylation, sulfonation, reductive amination, alkylation, and Suzuki or Buchwald-Hartwig cross-coupling reactions. The efficacy of this strategy was exemplified by the preparation of an original pilot library of di- and trisubstituted benzazepines obtained in high purity as assessed by both 1H NMR and liquid chromatography/mass spectrometry (LC/MS) analysis. PMID- 17358082 TI - Bioactive lignans from Peperomia duclouxii. AB - Six new lignans (1-6), along with 14 known compounds, were obtained from Peperomia duclouxii. The new structures were elucidated mainly by the analysis of their NMR and MS data. The absolute configurations of 1-6 were determined by comparing their optical rotations or CD spectra with those of known compounds. In cytotoxic and MDR reversal cell activity assays, compound 3 showed cancer cell growth inhibitory activity against VA-13 and HepG2 cells, with IC50 values of 5.3 and 13.2 microg/mL, and more potent effects on calcein accumulation in MDR 2780AD cells than verapamil, a positive control. Compound 6 showed anti-inflammatory activity using an ICAM-1 assay (induction of the intercellular adhesion molecule 1), stimulated by IL-1alpha and TNF-alpha. PMID- 17358084 TI - Diversity-oriented asymmetric synthesis of hapalosin: construction of three small C9/C4/C3-modified hapalosin analogue libraries. AB - A flexible approach to the beta-hydroxy gamma-amino acid residue (fragment C) of hapalosin has been developed on the basis of the the regio- and diastereoselective Grignard reaction. The method allows the introduction of different side chains at the C9 of hapalosin. Asymmetric syntheses of hapalosin (1a), 9-homohapalosin (1b), 9-i-butyl-hapalosin (1c), 8-epi-hapalosin (epi-1a), and three small libraries diversified at C9 (3-member, 1L3), C9/ C4 (9-member, 1L9), or C9/C4/C3 (27-member, 1L27) have been produced using this method. PMID- 17358085 TI - Different interactions between the two sides of purple membrane with atomic force microscope tip. AB - Atomic force microscopy (AFM) is known to be capable of measuring local surface charge density based on the DLVO model. However, it has failed to distinguish charge density difference between the extracellular and cytoplasmic sides of purple membrane (PM) in previous studies. In this paper, tapping-mode AFM with thioglycolate-modified tips was used to image PM in buffers of different salt concentrations. When imaged in 25 mM KCl buffer, the topography of membranes appeared to be of two different types, one flat and the other domelike. Such a difference was not observed in buffers of high salt concentrations. This suggests that the topography variation results from differences in electrostatic interaction between the AFM tip and the different membrane surfaces. With images of papain-digested PM and high-resolution images of membrane surface structure, we proved that the membrane surfaces with flat topography were on the extracellular side while the surfaces with domelike topography were on the cytoplasmic side. Hence, this provides a straightforward method to distinguish the two sides of PM without the requirement of high-resolution imaging. Force distance curves clearly demonstrated the different tip-sample interactions. The force curves recorded on the extracellular side of PM were consistent with the DLVO model, so its surface charge density can be estimated well. However, the curves recorded on the cytoplasmic side had a much longer decay length, which is supposed to be relevant to the flexibility of the C-terminus of bacteriorhodopsin (bR). PMID- 17358086 TI - Efficiently stabilized spherical vaterite CaCO3 crystals by carbon nanotubes in biomimetic mineralization. AB - Carbon nanotubes were used to induce the formation of spherical vaterite crystals and stabilize the metastable crystals in the biomimetic mineralization of CaCO3 for the first time. It was found that carboxyl-functionalized multiwalled/single walled carbon nanotubes (MWNT-COOH/SWNT-COOH) can favor the formation of spherical vaterite crystals and stabilize the crystals. In the presence of CNT COOH, CaCO3 vaterite crystals with diameters of ca. 1-7 microm coated and embedded with the carbon nanotubes (CNTs) were obtained in 30 min by adding Na2CO3 aqueous solution to the aqueous solution of CaCl2. The spherical vaterite crystals covered by the carboxylic CNTs can exist stably in water for a week. Carboxylic-polymer-functionalized CNTs can also facilitate the formation of spherical vaterite crystals, whereas the formed crystals completely transformed into thermodynamically stable calcite crystals in water within 10 h. "Offline" TEM observations of the mineralization process of CaCO3 in the presence of CNT COOH or pristine CNTs revealed the stability mechanism of vaterite crystals with carboxylic CNTs. The crystals nucleate at the carboxyl groups of CNT-COOH, grow around the CNTs, and finally form spherical vaterite crystals embedded and covered by the CNTs. The strong interaction between CNT-COOH and crystals together with the strong mechanical strength of CNTs stabilizes the formed vaterite crystals and makes them difficult to dissolve in water. These findings announce that nanomaterials could strongly influence the mineralization of biomineralization matters, which may help us prepare novel biomaterials and bionanomaterials. PMID- 17358087 TI - Photochemical grafting and activation of organic layers on glassy carbon and pyrolyzed photoresist films. AB - Organic films have been grafted to polished glassy carbon (GC) and as-prepared pyrolyzed photoresist film (PPF) by photolysis of alkenes and an alkyne. The alkene or alkyne is spin-coated onto the carbon surface and photolyzed in air at 254 nm. Characterization by water contact angle measurements, depth profiling and surface roughness measurements using atomic force microscopy (AFM), and electrochemistry reveal that for most modifiers a loosely packed monolayer is grafted to the surface. Grafted layers of 1-decene were further reacted by drop coating with oxalyl chloride and photolyzing at 254 nm in air. The procedure adds acid chloride groups to the film. Amines were attached to these films via amide bond formation, and were characterized by electrochemistry and assembly of citrate-capped gold nanoparticles. Amines were also coupled to photografted 1 undecylenic acid layers and to carboxyphenyl layers prepared by electroreduction of the corresponding diazonium salt. Quantitative analysis using electrochemistry established that the highest concentration of amines was attached to the oxalyl chloride treated film, and that a higher concentration of amines was attached via reaction with the photografted 1-undecylenic acid layer than the electrografted carboxyphenyl layer. Thus photografting and photoreaction with oxalyl chloride are simple methods for generating amine-reactive tethers on GC and PPF surfaces. PMID- 17358088 TI - Formation of hierarchical molecular assemblies from poly(oxypropylene)-segmented amido acids under AFM tapping. AB - Molecular self-aligning of amphiphilic molecules into bundles with a constant width of 7-13 nm was observed under tapping-mode atomic force microscopy (TM AFM). The requisite amphiphile, a poly(oxypropylene)-trimellitic amido acid sodium salt, is constituted of a symmetric amido acid structure with potential noncovalent forces of ionic charges, hydrogen bonds, pi-pi aromatic stacking, and hydrophobic interactions for intermolecular interaction. The amphiphiles are able to self-align into orderly hierarchical assemblies after simply being dissolved in water and dried under spin-coated evaporation. Under the TM-AFM tapping process, the bundles increased their length from an initial 20 to 600 nm. A sequential TM-AFM scanning and interval heating process was designed to probe the morphological transformations from the molecular bundles to lengthy strips (nearly micrometer scale) and to columns (with 5-7 nm spacing between the parallel strips). The formation of hierarchical arrays via molecular stretching, aligning, and connecting to each other was simultaneously observed and accelerated under the TM-AFM vibration energy. The molecular self-alignment caused by vibrations is envisioned to be a potential methodology for manipulating molecules into assembled templates, sensors, and optoelectronic devices. PMID- 17358089 TI - Sub-micrometer patterning of proteins by electric lithography. AB - We report in this paper an electric lithographic (EL) technique to generate protein patterns with sub-micrometer resolution on a poly(N-tBOC-2-aminoethyl methacrylate) surface. In the EL process, an electric potential is applied between metal patterns on a mask and the poly(N-tBOC-2-aminoethyl methacrylate) layer to electrochemically induce the dissociation of the tBOC from the amine functional groups. Proteins are then selectively attached to the amine functional groups in the modified polymer surface areas to form protein patterns. This technique can reliably generate high-resolution protein patterns down to approximately 300 nm on the polymer surface at a high speed with a simple process/system. PMID- 17358090 TI - High capacity, charge-selective protein uptake by polyelectrolyte brushes. AB - Surface plasmon resonance was used to measure binding of proteins from solution to poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes end-grafted from gold surfaces by atom transfer radical polymerization (ATRP). PDMAEMA brushes were prepared with a variety of grafting densities and degrees of polymerization. These brushes displayed charge selective protein uptake. The extent of uptake for net negatively charged bovine serum albumin (BSA) scaled linearly with the surface mass concentration of grafted PDMAEMA, regardless of grafting density. BSA was bound at a constant ratio of 120 DMAEMA monomer units per protein molecule for all brushes examined. The equivalent three-dimensional concentration of BSA bound in the brush (i.e., the bound BSA surface excess concentration divided by the brush thickness) decreased monotonically with decreasing grafting density. The concentration of BSA bound within brushes prepared at higher grafting densities was comparable with the aqueous protein solubility limit. BSA desorption from the brush required changes in solution pH and/or ionic strength to eliminate its net electrostatic attraction to PDMAEMA. Net positively charged lysozyme was completely rejected by the PDMAEMA brushes. PMID- 17358091 TI - Direct observation of the deformation and the band gap change from an individual single-walled carbon nanotube under uniaxial strain. AB - We have fabricated a new device for applying uniaxial strain to an individual suspended SWNT, and the form and the photoluminescence (PL) of an individual suspended SWNT under stretching are investigated. The processes of deformation and break of a SWNT under stretching are directly observed by scanning electron microscopy (SEM). From the PL measurements, the emission energy shifts due to the band gap change are measured under the elastic strain. The behaviors of the emission shifts can be related to the deformation processes observed by SEM. Moreover, the emission intensity reduction due to the elastic strain of a SWNT is also observed just before breaking. PMID- 17358092 TI - ZnO nanowire UV photodetectors with high internal gain. AB - ZnO nanowire (NW) visible-blind UV photodetectors with internal photoconductive gain as high as G approximately 108 have been fabricated and characterized. The photoconduction mechanism in these devices has been elucidated by means of time resolved measurements spanning a wide temporal domain, from 10-9 to 102 s, revealing the coexistence of fast (tau approximately 20 ns) and slow (tau approximately 10 s) components of the carrier relaxation dynamics. The extremely high photoconductive gain is attributed to the presence of oxygen-related hole trap states at the NW surface, which prevents charge-carrier recombination and prolongs the photocarrier lifetime, as evidenced by the sensitivity of the photocurrrent to ambient conditions. Surprisingly, this mechanism appears to be effective even at the shortest time scale investigated of t < 1 ns. Despite the slow relaxation time, the extremely high internal gain of ZnO NW photodetectors results in gain-bandwidth products (GB) higher than approximately 10 GHz. The high gain and low power consumption of NW photodetectors promise a new generation of phototransistors for applications such as sensing, imaging, and intrachip optical interconnects. PMID- 17358094 TI - Prevention of osteoporosis: four-year follow-up of a cohort of postmenopausal women treated with an ossein-hydroxyapatite compound. AB - BACKGROUND: The long-term effects of ossein-hydroxyapatite compound (OHC), a drug used for osteoporosis prevention, have not been previously reported. The aim of this study was to assess the long-term efficacy of OHC in postmenopausal women with bone mineral density (BMD) in the osteopenia range. METHODS: We performed a retrospective 4-year follow-up study in a primary-care setting to assess changes in BMD in a cohort of 112 postmenopausal women included in an osteoporosis programme that included health and dietary advice and who were treated with OHC 1660mg every 12 hours. BMD was measured annually in the distal part of the forearm, with T- and Z-score values being calculated for trabecular and total bone. RESULTS: A progressive and statistically significant increase in BMD was observed in trabecular and total T- and Z-score mean values. At baseline, mean +/ SD trabecular T- and Z-scores were -1.27 +/- 0.7 and -1.03 +/- 0.7, respectively, and -0.86 +/- 0.7 and -0.62 +/- 0.7, respectively, at the end of the 4-year follow-up period (both p < 0.0001). Mild constipation was observed in 3.2% of patients during the follow-up period. CONCLUSION: Ossein-hydroxyapatite compound could be an effective and safe agent for the prevention of bone loss in postmenopausal osteopenic women, with significant increases in BMD being observed in this group of patients. PMID- 17358093 TI - Vibrational response of Au-Ag nanoboxes and nanocages to ultrafast laser-induced heating. AB - Time-resolved spectroscopy has been used to investigate the vibrational properties of hollow cubic nanoparticles: Au-Ag nanoboxes and nanocages. In these experiments, laser-induced heating was used to coherently excite the breathing vibrational modes of the particle. The vibrational periods scale with the edge length of the particle and the nanocages and nanoboxes showing equivalent responses despite a large difference in their morphology. The measured vibrational periods are compared to finite element calculations, where the particles are modeled as a hollow cube, with the principle crystal axes parallel to the sides of the cube. Very good agreement is obtained between the calculations and the experimental data, with the experimental frequencies being slightly lower than the calculated values (by approximately 7%). These results demonstrate the importance of accurately modeling the particles in order to interpret experimental data. PMID- 17358095 TI - Pharmacoeconomic analysis of liposomal amphotericin B versus voriconazole for empirical treatment of febrile neutropenia. AB - BACKGROUND: Liposomal amphotericin B (LAmB) has demonstrated similar efficacy to conventional amphotericin B for antifungal treatment in patients with febrile neutropenia; however, it is not without toxicities and is associated with a high acquisition cost. Despite this high cost, LAmB has been shown to have a pharmacoeconomic advantage over less expensive agents. Voriconazole is a potential alternative for empirical antifungal treatment of febrile neutropenia. The objective of this study was to assess the economic outcomes of voriconazole versus LAmB in patients with fever and neutropenia. METHODS: A decision analytical model was developed from a hospital perspective based on a 2-year (2002-2003) review of outcomes and prescribing practices in febrile neutropenic patients at a tertiary care medical centre. Literature reports and expert opinion were used to further populate the model. Sensitivity analyses and Monte Carlo simulation enhanced the robustness of the model through variation of all probabilities and costs that populated the model. RESULTS: Sixty-three cases were evaluated in the retrospective review. Thirty-two were initially given voriconazole and 31 were given LAmB. Patient demographic data were similar in each group. In the base case, patients initially given voriconazole displayed a 27% reduction in overall treatment cost over patients initially given LAmB (14,950 vs 20,591 $US). Sensitivity analysis determined that the cost advantage in the voriconazole arm was maintained over a wide range of costs and probabilities. Variance in the cost of nephrotoxicity and medication cost did not significantly alter results. Monte Carlo simulation determined the voriconazole arm to be the optimal path in 65% of cases. CONCLUSION: The decision model indicated that use of voriconazole as the preferred antifungal agent in adult haematology patients with febrile neutropenia should result in lower overall treatment costs relative to LAmB. PMID- 17358096 TI - Relative bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension. AB - BACKGROUND AND OBJECTIVE: Maintenance of effective drug concentrations is essential for adequate treatment of epilepsy. Some antiepileptic drugs can be successfully administered rectally when the oral route of administration is temporarily unavailable. Oxcarbazepine is a newer antiepileptic drug that is rapidly converted to a monohydroxy derivative, the active compound. This study aimed to characterise the bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension using a randomised, crossover design in ten healthy volunteers. METHODS: Two subjects received 300 mg doses of oxcarbazepine suspension via rectal and oral routes and eight received 450 mg doses. A washout period of at least 2 weeks elapsed between doses. The rectal dose was diluted 1:1 with water. Blood samples and urine were collected for 72 hours post-dose. Adverse effects were assessed at each blood collection time point using a self-administered questionnaire. Plasma was assayed for oxcarbazepine and monohydroxy derivative; urine was assayed for monohydroxy derivative and monohydroxy derivative-glucuronide. Maximum plasma concentration (C(max)) and time to reach C(max) (t(max)) were obtained directly from the plasma concentration-time curves. The areas under the concentration-time curve (AUCs) were determined via non-compartmental analysis. Relative bioavailability was calculated and the C(max) and AUCs were compared using Wilcoxon signed-rank tests. RESULTS: Mean relative bioavailability calculated from plasma AUCs was 8.3% (SD 5.5%) for the monohydroxy derivative and 10.8% (SD 7.3%) for oxcarbazepine. Oxcarbazepine and monohydroxy derivative C(max) and AUC values were significantly lower following rectal administration (p < 0.01). The total amount of monohydroxy derivative excreted in the urine following rectal administration was 10 +/- 5% of the amount excreted following oral administration. Oral absorption was consistent with previous studies. The most common adverse effects were headache and fatigue with no discernible differences between routes. CONCLUSIONS: Monohydroxy derivative bioavailability following rectal administration of oxcarbazepine suspension is significantly lower than following oral administration, most likely because of poor oxcarbazepine water solubility. It is unlikely that adequate monohydroxy derivative concentrations can be achieved with rectal administration of diluted oxcarbazepine suspension. PMID- 17358097 TI - Influence of cytochrome P450 (CYP) 3A5 polymorphisms on the pharmacokinetics of lansoprazole enantiomers in CYP2C19 extensive metaboliser renal transplant recipients. AB - BACKGROUND AND OBJECTIVE: Lansoprazole is extensively metabolised by cytochrome P450 (CYP) 2C19 and CYP3A4. The purpose of this study was to evaluate the effects of CYP3A5 polymorphism (A6986G) on the pharmacokinetics of lansoprazole enantiomers in renal transplant recipients who are CYP2C19 extensive metabolisers (EMs). METHODS: Among 40 Japanese CYP2C19 EMs, 20 had the CYP3A5*1 allele (*1/*1 in two subjects and *1/*3 in 18 subjects) and 20 had the CYP3A5*3/*3 genotype. After repeated oral doses of racemic lansoprazole 30mg once daily for 28 days, plasma concentrations of lansoprazole enantiomers were determined using high performance liquid chromatography. RESULTS: The mean area under the plasma concentration-time curves from 0 to infinity (AUC(infinity)) of (R)- and (S) lansoprazole in recipients with the CYP3A5*1 allele were 3145 and 384 ng * h/mL, respectively, compared with 4218 and 587 ng * h/mL in recipients with the CYP3A5*3/*3 genotype. The AUC(infinity) and the maximum plasma concentration of (R)- and (S)-lansoprazole in subjects with the CYP3A5*3/*3 genotype were greater than subjects with CYP3A5*1/*1 + *1/*3 alleles. The mean R/S ratio for AUC of lansoprazole in each CYP3A5 genotype group was the same (12.6). CONCLUSION: Our findings show that CYP3A5 genotype is not an important determinant of enantioselective disposition of lansoprazole. Based on our results and those of previous studies, the enantioselective disposition of lansoprazole appears to be primarily influenced by enantioselective metabolism by CYP2C19 rather than by CYP3A. PMID- 17358098 TI - Efficacy and tolerability of oxycodone hydrochloride controlled-release tablets in moderate to severe cancer pain. AB - BACKGROUND AND OBJECTIVE: Oxycodone is a semisynthetic opioid analgesic drug classed as a strong opioid. The controlled-release oxycodone tablet formulation (OCRT) was approved in China in 2004 for management of moderate to severe cancer pain. Few data about the efficacy of OCRT and clinical outcomes in Chinese patients taking this drug are available. The purpose of this study was to evaluate the efficacy and tolerability of this drug for relief of moderate to severe cancer pain in Chinese patients. METHODS: This was a prospective, open label, multicentre clinical trial carried out in ten hospitals in Zhejiang Province, China. Patients with cancer pain with a score > or =4 (numerical rating scale) were enrolled. They received oral OCRT at an initial dosage of 5mg every 12 hours for patients scoring 4-6 and 10mg every 12 hours for patients scoring > or =7. Doses were then titrated on an individual basis. Onset of analgesic action, pain score and quality-of-life (QOL) scores - including items measuring family understanding and support, sleep, mental state, appetite, fatigue, and activities of daily life - were evaluated. Adverse effects were also documented. RESULTS: 216 patients (126 males and 90 females) aged 22-84 years were enrolled. The total mean OCRT dosage was 445.2 +/- 361.6mg (range 130-2320mg). The daily dosages of the vast majority of cases (89%) were between 10mg and 30mg. Onset of analgesic action occurred within 1 hour in 198 cases (91.7%) following administration of OCRT. 82.4% of cases were titrated to a steady dosage level within 2 days following administration of the first dose of medication. Pain score decreased significantly (p < 0.01) from 7.1 +/- 1.2 at baseline to 2.3 +/- 1.2 one week after starting medication and 1.8 +/- 0.9 four weeks after starting medication. Scores on all six QOL items increased significantly (p < 0.01) compared with baseline but showed varying rates of improvement. Adverse events included constipation, nausea, vomiting, drowsiness and dysuria. These were noted most frequently in the first week (25.5% of patients) and lessened over time. No severe adverse events were noted. CONCLUSION: We conclude that OCRT is well tolerated and effective in controlling moderate to severe cancer pain in Chinese patients. PMID- 17358099 TI - Effects of esmolol, lidocaine and fentanyl on haemodynamic responses to endotracheal intubation: a comparative study. AB - BACKGROUND AND OBJECTIVE: Predicting the haemodynamic changes that may result in myocardial ischaemia for patients undergoing laryngoscopy and tracheal intubation will help to avoid events that trigger ischaemia and allow immediate treatment. The objective of this study was to compare the effects of esmolol with those of lidocaine (lignocaine) and fentanyl on prevention of tachycardia and hypertension caused by endotracheal intubation. METHODS: This was a prospective, randomised, double-blind study. The study was conducted at the Adnan Menderes University Hospital in Aydin, Turkey and involved 120 patients of American Society of Anesthesiologists physical status I or II aged 20-50 years. The patients were randomised into four equal groups. The control group (group C) received dextrose 5% 5 mL, the esmolol group (group E) received esmolol 1.5 mg/kg, the fentanyl group (group F) received fentanyl 1 microg/kg and the lidocaine group (group L) received lidocaine 1.5 mg/kg 2 minutes before endotracheal intubation. Heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were recorded before and after induction of anaesthesia, immediately after intubation, and 1, 3, 5, 7 and 10 minutes after intubation. RESULTS: Compared with control, HR decreased significantly in group E after induction, immediately after intubation and 1 minute after intubation (p < 0.0083). In group F there was an increase in MAP immediately after intubation, but the increase was less than in other groups. Compared with control, RPP decreased significantly in groups E and F after induction, immediately after intubation and 1 minute after intubation (p < 0.0083). RPP was significantly lower in group E than in controls and group L 3 minutes after intubation (p < 0.0083), and it was significantly lower in group F than in controls 10 minutes after intubation (p < 0.0083). CONCLUSION: It can be concluded that administration of esmolol 1.5 mg/kg 2 minutes before intubation prevents tachycardia and an increase in RPP caused by laryngoscopy and tracheal intubation, and can be beneficial when administered before laryngoscopy and tracheal intubation in patients with tachycardia. PMID- 17358102 TI - Force mobilization and generalized isostaticity in jammed packings of frictional grains. AB - We show that in slowly generated two-dimensional packings of frictional spheres, a significant fraction of the friction forces lie at the Coulomb threshold-for small pressure p and friction coefficient mu , about half of the contacts. Interpreting these contacts as constrained leads to a generalized concept of isostaticity, which relates the maximal fraction of fully mobilized contacts and contact number. For p-->0 , our frictional packings approximately satisfy this relation over the full range of mu . This is in agreement with a previous conjecture that gently built packings should be marginal solids at jamming. In addition, the contact numbers and packing densities scale with both p and mu . PMID- 17358100 TI - Insulin detemir results in less weight gain than NPH insulin when used in basal bolus therapy for type 2 diabetes mellitus, and this advantage increases with baseline body mass index. AB - OBJECTIVE: Weight gain during insulin therapy can be a challenging problem in already overweight type 2 diabetes mellitus patients, affecting treatment compliance and long-term prognosis. The analogue insulin detemir has been reported to have a weight-sparing effect compared with other basal insulins. This pooled analysis investigated whether this potential advantage is related to body mass index (BMI) when insulin detemir is used as the basal component of basal bolus therapy. METHODS: Data were pooled from two randomised, parallel group trials of 22 and 24 weeks' duration, in which 900 insulin-treated patients with type 2 diabetes mellitus had their treatment intensified to basal-bolus therapy. Patients received once- or twice-daily insulin detemir or neutral protamine Hagedorn (NPH) insulin in conjunction with insulin aspart or human soluble insulin at meal times. RESULTS: Patients treated with insulin detemir had minimal weight gain (mean <1 kg), regardless of their BMI at entry (estimated slope 0.032), whereas, in patients treated with NPH insulin, weight gain increased as baseline BMI increased (estimated slope 0.075, p = 0.025). Indeed, NPH insulin treated patients with the largest BMI (>35 kg/m(2)) gained the most weight (mean of ~2.4 kg). In contrast, insulin detemir-treated patients with a BMI >35 kg/m(2) lost weight (mean of ~ -0.5 kg). Glycaemic control was similar with the two treatments. CONCLUSION: Insulin detemir may provide a clinical advantage in terms of reduced weight gain in the treatment of overweight patients with type 2 diabetes. PMID- 17358101 TI - Pantoprazole on-demand effectively treats symptoms in patients with gastro oesophageal reflux disease. AB - OBJECTIVE: The efficacy of pantoprazole as on-demand therapy for the long-term management of patients with mild gastro-oesophageal reflux disease (GORD) has been demonstrated in clinical studies. In this study, the efficacy of pantoprazole 20mg and esomeprazole 20mg as on-demand therapy for relief of symptoms of mild GORD was compared. METHODS: Patients with reflux oesophagitis grade A or B (Los Angeles classification) or endoscopy-negative reflux disease (enGORD) were treated with pantoprazole 20mg once daily for 28 days during the acute phase (AP, n = 236). Patients without heartburn during the final 3 days of the AP entered the long-term phase (LTP, n = 199) and were randomised to either pantoprazole 20mg or esomeprazole 20mg as on-demand treatment for 6 months. Antacids were provided as rescue medication during this phase. The mean intensities of the symptoms of heartburn, acid eructation and pain on swallowing, both separately and as a combined symptom score, together with the mean duration of these symptoms during on-demand treatment, were compared between the two treatment groups. The number of tablets taken was also compared. RESULTS: After 4 weeks of treatment with pantoprazole, 87.3% of patients had relief from heartburn, 74.1% from epigastric pain and 80.8% from acid eructation, according to the investigator assessment. A total of 236 patients were eligible for the on demand phase. Based on patient diary data, on-demand treatment with pantoprazole resulted in significantly lower mean intensity of heartburn compared with that in the esomeprazole group (1.12 for pantoprazole and 1.32 for esomeprazole, respectively [p = 0.012], in the intention-to-treat [ITT] population). The mean symptom intensities of acid eructation and pain on swallowing, together with the duration of these symptoms, were comparable in the two treatment groups. The combined symptom score of the three symptoms heartburn, acid eructation and pain on swallowing was numerically lower in the pantoprazole group compared with the esomeprazole group (1.72 vs 1.99, respectively, in the ITT population). Tablet intake was comparable in both groups. Relief of symptoms in Helicobacter pylori positive and -negative patients was also similar in both treatment groups. Both treatments were well tolerated with a good safety profile. CONCLUSION: On-demand therapy with either pantoprazole 20mg or esomeprazole 20mg is a comparably effective treatment strategy for the long-term treatment of non-erosive and mild GORD. However, the mean intensity of heartburn was significantly lower with pantoprazole treatment. PMID- 17358103 TI - Probing surface characteristics of diffusion-limited-aggregation clusters with particles of variable size. AB - We develop a technique for probing the harmonic measure of a diffusion-limited aggregation (DLA) cluster surface with variable-size particles and generate 1000 clusters with 50 x 10(6) particles using an original off-lattice killing-free algorithm. Taking, in sequence, the limit of the vanishing size of the probing particles and then sending the growing cluster size to infinity, we achieve unprecedented accuracy in determining the fractal dimension D=1.7100(2) crucial to the characterization of the geometric properties of DLA clusters. PMID- 17358104 TI - Critical exponents in metastable decay via quantum activation. AB - We consider decay of metastable states of forced vibrations of a quantum oscillator close to the bifurcation points where the states disappear. Decay occurs via quantum activation over a quasienergy barrier, a mechanism that differs from both tunneling and thermal activation. The decay probability W scales with the distance eta to the bifurcation point as /ln W/ proportional to eta(xi). The exponent xi is found for a resonantly driven oscillator and an oscillator modulated at nearly twice its eigenfrequency. PMID- 17358105 TI - Current behavior of a quantum Hamiltonian ratchet in resonance. AB - We investigate the ratchet current that appears in a kicked Hamiltonian system when the period of the kicks corresponds to the regime of quantum resonance. In the classical analog, a spatial-temporal symmetry should be broken to obtain a net directed current. It was recently discovered that in quantum resonance the temporal symmetry can be kept, and we prove that breaking the spatial symmetry is a necessary condition to find this effect. Moreover, we show numerically and analytically how the direction of the motion is dramatically influenced by the strength of the kicking potential and the value of the period. By increasing the strength of the interaction this direction changes periodically, providing us with un-expected source of current reversals in this quantum model. These reversals depend on the kicking period also, though this behavior is theoretically more difficult to analyze. Finally, we generalize the discussion to the case of a nonuniform initial condition. PMID- 17358106 TI - Condensates in driven aggregation processes. AB - We investigate aggregation driven by mass injection. In this stochastic process, mass is added with constant rate r and clusters merge at a constant total rate 1 , so that both the total number of clusters and the total mass steadily grow with time. Analytic results are presented for the three classic aggregation rates K{i,j} between clusters of size i and j . When K{i,j}=const , the cluster size distribution decays exponentially. When K{i,j} proportional, i+j or K{i,j} proportional, ixj , there are two phases: (i) a condensate phase with a condensate containing a finite fraction of the mass in the system as well as finite clusters and (ii) a cluster phase with finite clusters only. For K{i,j} proportional, i+j , the cluster size distribution, c{k} , has a power-law tail, c{k} approximately k;{-gamma} in either phase. The exponent is a nonmonotonic function of the injection rate gamma=r(r-1) in the condensate phase r<2 and gamma=r in the cluster phase r>2 . PMID- 17358107 TI - Synchronization transition of heterogeneously coupled oscillators on scale-free networks. AB - We investigate the synchronization transition of the modified Kuramoto model where the oscillators form a scale-free network with degree exponent lambda . An oscillator of degree k_{i} is coupled to its neighboring oscillators with asymmetric and degree-dependent coupling in the form of Jk_{i};{eta-1} . By invoking the mean-field approach, we find eight different synchronization transition behaviors depending on the values of eta and lambda , and derive the critical exponents associated with the order parameter and the finite-size scaling in each case. The synchronization transition point J_{c} is determined as being zero (finite) when eta>lambda-2 (eta4 , FSS of the d=5 Ising model no longer obeys the conventional scaling relation. Rather, it is expected that the FSS behavior depends on the geometry of the embedding space (boundary condition). In this paper, we consider a cylindrical geometry and explore its influence on the correlation length xi=L;{Omega}f(L;{y_{t};{*}},HL;{y_{h};{*}}) with system size L , reduced temperature , and magnetic field H ; the indices y_{t,h};{*} and Omega characterize FSS. For that purpose, we employed the transfer-matrix method with Novotny's technique, which enables us to treat an arbitrary (integral) number of spins, N=8,10,...,28 ; note that, conventionally, N is restricted in N(=L;{d 1})=16,81,256,... . As a result, we estimate the scaling indices as Omega=1.40(15) , y_{t};{*}=2.8(2) , and y_{h};{*}=4.3(1) . Additionally, postulating Omega=43 , we arrive at y_{t};{*}=2.67(10) and y_{h};{*}=4.0(2) . These indices differ from the naively expected ones Omega=1 , y_{t};{*}=2 and y_{h};{*}=3 . Rather, our data support the generic formulas Omega=(d-1)3 , y_{t};{*}=2(d-1)3 , and y_{h};{*}=d-1 , advocated for a cylindrical geometry in d4 . PMID- 17358110 TI - Inverse melting in lattice-gas models. AB - Inverse melting is the phenomenon, observed in both helium isotopes, by which a crystal melts when cooled at constant pressure. I investigate discrete-space analogs of inverse melting by means of two instances of a triangular-lattice-gas system endowed with a soft-core repulsion and a short-ranged attraction. To reconstruct the phase diagram, I use both transfer-matrix and Monte Carlo methods, as well as low-temperature series expansions. In one case, a phase behavior reminiscent of helium emerges, with a loose-packed phase (which is solidlike for low temperatures and liquidlike for high temperatures) extending down to zero temperature for low pressures and the possibility of melting the close-packed solid by isobaric cooling. At variance with previous model studies of inverse melting, the driving mechanism of the present phenomenon is mainly geometrical, related to the larger free-energy cost of a "vacancy" in the loose packed solid than in the close-packed one. PMID- 17358111 TI - Extension of scaled particle theory to inhomogeneous hard particle fluids. III. Entropic force exerted on a cavity that intersects a hard wall. AB - We present a further development of an inhomogeneous scaled particle theory (I SPT) for hard particle fluids confined by hard walls, such that the reversible work of cavity insertion can now be determined for all cavities that intersect one of the walls. Building upon a previous version of I-SPT [D. W. Siderius and D. S. Corti, Phys. Rev. E, 71, 036141 (2005)], a new function, F[over ] , is introduced, which is proportional to the net force on the surface of the cavity in the direction normal to the wall. The reversible work of cavity insertion is then determined by an integral over the force required to "push" the cavity of fixed size into the fluid starting from a position behind the wall. An exact relation for F[over ] at certain cavity locations and radii is derived and an accurate interpolation scheme is proposed for the computation of F[over ] beyond these exact limits. The chosen interpolation incorporates a large number of exact and nearly exact conditions, several of which follow from the surface thermodynamics of macroscopic cavities. Work predictions using F[over ] are highly accurate as compared to simulation results at low to moderate fluid densities. Good agreement still persists at densities near the hard-sphere freezing transition. The interpolation of F[over ] is also used to estimate the depletion force between a hard sphere solute and the wall. The I-SPT entropic force predictions are in good agreement with simulation results presented in the literature. Due to its reliance upon physical and geometric arguments, I-SPT provides important insights into the origin of various depletion effects such as how the interplay between geometry and the varying local density at the cavity surface gives rise to the appearance of multiple attractive regions at intermediate solute sizes and a universal repulsive region, both within solute to wall separations that are less than the diameter of a solvent particle. Finally, all of the scaled particle theory-based methods presented here can, in principle, be extended to describe hard particle fluids confined by nonplanar surfaces, thereby providing estimates of the depletion force between a solute and a variety of surfaces of interest. PMID- 17358112 TI - Critical behavior of random fibers with mixed Weibull distribution. AB - A random fiber bundle model with a mixed Weibull distribution is studied under the global load sharing scheme. The mixed model consists of two sets of fibers. The threshold strength of one set of fibers is randomly chosen from a Weibull distribution with a particular Weibull index, and another set of fibers with a different index. The mixing tunes the critical stress of the bundle and the variation of critical stress with the amount of mixing is determined using a probabilistic method where the external load is increased quasistatically. In a special case which we illustrate, the critical stress is found to vary linearly with the mixing parameter. The critical exponents and power-law behavior of burst avalanche size distribution is found to remain unaltered due to mixing. PMID- 17358113 TI - Piston dynamics from a microcanonical ensemble. AB - The dynamical behavior of a system consisting of a (heavy) piston and two rectangular boxes, each containing two hard disks and in contact with the piston, is studied based on a projection operator method for a microcanonical ensemble. We derive a coupled set of nonlinear equations for slow variables of the system and solve it to confirm that our theory with no adjustable parameters reproduces experimental results fairly well. Some limitations of the theory are discussed from the viewpoint of the separation of slow and fast time scales and ergodicity. PMID- 17358114 TI - Finite-size effect in persistence in random walks. AB - We have investigated the random walk problem in a finite system and studied the crossover induced in the persistence probability by the system size. Analytical and numerical work show that the scaling function is an exponentially decaying function. We consider two cases of trapping, one by a box of size L and the other by a harmonic trap. Our analytic calculations are supported by numerical works. We also present numerical results on the harmonically trapped randomly accelerated particle and the randomly accelerated particle with viscous drag. PMID- 17358115 TI - Maximum entropy principle explains quasistationary states in systems with long range interactions: the example of the Hamiltonian mean-field model. AB - A generic feature of systems with long-range interactions is the presence of quasistationary states with non-Gaussian single particle velocity distributions. For the case of the Hamiltonian mean-field model, we demonstrate that a maximum entropy principle applied to the associated Vlasov equation explains known features of such states for a wide range of initial conditions. We are able to reproduce velocity distribution functions with an analytic expression which is derived from the theory with no adjustable parameters. A normal diffusion of angles is detected, which is consistent with Gaussian tails of velocity distributions. A dynamical effect, two oscillating clusters surrounded by a halo, is also found and theoretically justified. PMID- 17358116 TI - Phase-ordering kinetics on graphs. AB - We study numerically the phase-ordering kinetics following a temperature quench of the Ising model with single spin-flip dynamics on a class of graphs, including geometrical fractals and random fractals, such as the percolation cluster. For each structure we discuss the scaling properties and compute the dynamical exponents. We show that the exponent a_{chi} for the integrated response function, at variance with all the other exponents, is independent of temperature and of the presence of pinning. This universal character suggests a strict relation between a_{chi} and the topological properties of the networks, in analogy to what is observed on regular lattices. PMID- 17358117 TI - Incorporating variability into an approximation formula for bond percolation thresholds of planar periodic lattices. AB - Approximation formulas to predict values for bond percolation thresholds of periodic graphs make use of certain features of lattice graphs such as dimension and average degree. We show that a relationship exists between the average and second-moment of the degree of a graph and the average degree of its line graph. Using this relationship together with the well-known bond-to-site transformation between the bond percolation model on a graph and the site percolation model on its line graph, we create a new approximation formula that improves the accuracy of bond percolation threshold predictions. PMID- 17358118 TI - Random trimer tilings. AB - We study tilings of the square lattice by linear trimers. For a cylinder of circumference m , we construct a conserved functional of the base of the tilings, and use this to block diagonalize the transfer matrix. The number of blocks increases exponentially with m . The dimension of the block corresponding to the largest eigenvalue is shown to grow as (32;{13});{m} . We numerically diagonalize this block for m0 , the ferromagnetic coupling, for given values of the crystal field. Then, the phase diagram of the system is obtained on the (kTJ_{1},J_{3}J_{1}) plane for given values of the crystal field and alpha=J_{2}J_{1} with q=4 corresponding to the square lattice in real lattice systems. It was found that the system presents both first- and second-order phase transitions, therefore, tricritical points. The paramagnetic phase was also divided into two phases, P+ and P_{-} , by studying the thermal behavior of the quadrupolar moments of the two layers. PMID- 17358120 TI - Effect of discontinuity in the threshold distribution on the critical behavior of a random fiber bundle. AB - The critical behavior of a random fiber bundle model with mixed uniform distribution of threshold strengths and global load sharing rule is studied with a special emphasis on the nature of distribution of avalanches for different parameters of the distribution. The discontinuity in the threshold strength distribution of fibers nontrivially modifies the critical stress as well as puts a restriction on the allowed values of parameters for which the recursive dynamics approach holds good. The discontinuity leads to a nonuniversal behavior in the avalanche size distribution for smaller values of avalanche size. We observe that apart from the mean field behavior for larger avalanches, a new behavior for smaller avalanche size is observed as a critical threshold distribution is approached. The phenomenological understanding of the above result is provided using the exact analytical result for the avalanche size distribution. Most interestingly, the prominence of nonuniversal behavior in avalanche size distribution depends on the system parameters. PMID- 17358121 TI - Biased random walks and propagation failure. AB - The critical value of the reaction rate able to sustain the propagation of an invasive front is obtained for general non-Markovian biased random walks with reactions. From the Hamilton-Jacobi equation corresponding to the mean field equation we find that the critical reaction rate depends only on the mean waiting time and on the statistical properties of the jump length probability distribution function and is always underestimated by the diffusion approximation. If the reaction rate is larger than the jump frequency, invasion always succeeds, even in the case of maximal bias. Numerical simulations support our analytical predictions. PMID- 17358122 TI - Intertime jump statistics of state-dependent Poisson processes. AB - A method to obtain the probability distribution of the interarrival times of jump occurrences in systems driven by state-dependent Poisson noise is proposed. Such a method uses the survivor function obtained by a modified version of the master equation associated to the stochastic process under analysis. A model for the timing of human activities shows the capability of state-dependent Poisson noise to generate power-law distributions. The application of the method to a model for neuron dynamics and to a hydrological model accounting for land-atmosphere interaction elucidates the origin of characteristic recurrence intervals and possible persistence in state-dependent Poisson models. PMID- 17358123 TI - Artifacts with uneven sampling of red noise. AB - The vast majority of sampling systems operate in a standard way: at each tick of a fixed-frequency master clock a digitizer reads out a voltage that corresponds to the value of some physical quantity and translates it into a bit pattern that is either transmitted, stored, or processed right away. Thus signal sampling at evenly spaced time intervals is the rule: however, this is not always the case, and uneven sampling is sometimes unavoidable. While periodic or quasiperiodic uneven sampling of a deterministic signal can reasonably be expected to produce artifacts, it is much less obvious that the same happens with noise: here I show that this is indeed the case only for long-memory noise processes, i.e., power law noises 1f;{alpha} with alpha>2 . The resulting artifacts are usually a nuisance although they can be eliminated with a proper processing of the signal samples, but they could also be turned to advantage and used to encode information. PMID- 17358124 TI - Finite-size effects on the behavior of the susceptibility in van der Waals films bounded by strongly absorbing substrates. AB - We study critical point finite-size effects in the case of the susceptibility of a film in which interactions are characterized by a van der Waals-type power law tail. The geometry is appropriate to a slablike system with two bounding surfaces. Boundary conditions are consistent with surfaces that both prefer the same phase in the low temperature, or broken symmetry, state. We take into account both interactions within the system and interactions between the constituents of the system and the material surrounding it. Specific predictions are made with respect to the behavior of 3He and 4He films in the vicinity of their respective liquid-vapor critical points. PMID- 17358125 TI - Experimental test of a new equality: measuring heat dissipation in an optically driven colloidal system. AB - Measurement of energy dissipation in small nonequilibrium systems is generally a difficult task. Recently, Harada and Sasa [Phys. Rev. Lett. 95, 130602 (2005)] derived an equality relating the energy dissipation rate to experimentally accessible quantities in nonequilibrium steady states described by the Langevin equation. Here, we show an experimental test of this new relation in an optically driven colloidal system. We find that this equality is validated to a fairly good extent, thus the irreversible work of a small system is estimated from readily obtainable quantities. PMID- 17358126 TI - Random sequential adsorption of shrinking or expanding particles. AB - We present a model of one-dimensional irreversible adsorption in which particles once adsorbed immediately shrink to a smaller size or expand to a larger size. Exact solutions for the fill factor and the particle number variance as a function of the size change are obtained. Results are compared with approximate analytical solutions. PMID- 17358127 TI - Advective transport in percolation clusters. AB - We simulate advective transport in bond percolation clusters at the critical point. We compute the histogram of flow speeds in each bond of the backbone and find the multifractal spectrum for two-dimensional lattices with linear dimension L2000 and in three dimensions for L250 . We demonstrate that in the limit of large systems all the negative moments of the velocity distribution become ill defined. However, to model transport, the velocity histogram should be weighted by the flux to obtain a well-defined mean travel time. Finally, we use continuous time random walk theory to demonstrate that anomalous transport is observed whose characteristics can be related to the multifractal properties of the system. PMID- 17358128 TI - Lattice melting and rotation in perpetually pulsating equilibria. AB - Systems whose potential energies consists of pieces that scale as r;{-2} together with pieces that scale as r;{2} , show no violent relaxation to Virial equilibrium but may pulsate at considerable amplitude forever. Despite this pulsation these systems form lattices when the nonpulsational "energy" is low, and these disintegrate as that energy is increased. The "specific heats" show the expected halving as the "solid" is gradually replaced by the "fluid" of independent particles. The forms of the lattices are described here for N18 and they become hexagonal close packed for large N . In the larger N limit, a shell structure is formed. Their large N behavior is analogous to a gamma=53 polytropic fluid with a quasigravity such that every element of fluid attracts every other in proportion to their separation. For such a fluid, we study the "rotating pulsating equilibria" and their relaxation back to uniform but pulsating rotation. We also compare the rotating pulsating fluid to its discrete counterpart, and study the rate at which the rotating crystal redistributes angular momentum and mixes as a function of extra heat content. PMID- 17358129 TI - Test to determine the Markov order of a time series. AB - The Markov order of a time series is an important measure of the "memory" of a process, and its knowledge is fundamental for the correct simulation of the characteristics of the process. For this reason, several techniques have been proposed in the past for its estimation. However, most of this methods are rather complex, and often can be applied only in the case of Markov chains. Here we propose a simple and robust test to evaluate the Markov order of a time series. Only the first-order moment of the conditional probability density function characterizing the process is used to evaluate the memory of the process itself. This measure is called the "expected value Markov (EVM) order." We show that there is good agreement between the EVM order and the known Markov order of some synthetic time series. PMID- 17358130 TI - Characteristics of the asymmetric simple exclusion process in the presence of quenched spatial disorder. AB - We investigate the effect of quenched spatial disordered hopping rates on the characteristics of the asymmetric simple exclusion process with open boundaries both numerically and by extensive simulations. Disorder averages of the bulk density and current are obtained in terms of various input and output rates. We study the binary and uniform distributions of disorder. It is verified that the effect of spatial inhomogeneity is generically to enlarge the size of the maximal current phase. This is in accordance with the mean-field results obtained by Harris and Stinchcombe [Phys. Rev. E 70, 016108 (2004)]. Furthermore, we obtain the dependence of the current and the bulk density on the characteristics of the disorder distribution function. It is shown that the impact of disorder crucially depends on the particle input and out rates. In some situations, disorder can constructively enhance the current. PMID- 17358131 TI - Statistics of return intervals in long-term correlated records. AB - We consider long-term correlated data with several distribution densities (Gaussian, exponential, power law, and log normal) and various correlation exponents gamma (0Delta_{c} approximately 1.65 and divergent for DeltaDelta_{c} . The scaling function of the distribution of the mass of the clusters as well as the geometrical correlation function are found to involve the scaling exponents of critical percolation. On the other hand, the divergence of the correlation length, xi(Delta) approximately (Delta-Delta_{c});{-nu} , with nu approximately 2 , is related to that of tricritical percolation. It is verified numerically that critical geometrical correlations transform conformally. PMID- 17358135 TI - Quantum master equations from classical Lagrangians with two stochastic forces. AB - We show how a large family of master equations, describing quantum Brownian motion of a harmonic oscillator with translationally invariant damping, can be derived within a phenomenological approach, based on the assumption that an environment can be simulated by two classical stochastic forces. This family is determined by three time-dependent correlation functions (besides the frequency and damping coefficients), and it includes as special cases the known master equations, whose dissipative part is bilinear with respect to the operators of coordinate and momentum. PMID- 17358136 TI - Jarzynski equality: connections to thermodynamics and the second law. AB - The one-dimensional expanding ideal gas model is used to compute the exact nonequilibrium distribution function. The state of the system during the expansion is defined in terms of local thermodynamics quantities. The final equilibrium free energy, obtained a long time after the expansion, is compared against the free energy that appears in the Jarzynski equality. Within this model, where the Jarzynski equality holds rigorously, the free energy change that appears in the equality does not equal the actual free energy change of the system at any time of the process. More generally, the work bound that is obtained from the Jarzynski equality is an upper bound to the upper bound that is obtained from the first and second laws of thermodynamics. The cancellation of the dissipative (nonequilibrium) terms that result in the Jarzynski equality is shown in the framework of response theory. This is used to show that the intuitive assumption that the Jarzynski work bound becomes equal to the average work done when the system evolves quasistatically is incorrect under some conditions. PMID- 17358137 TI - Spinodal of supercooled polarizable water. AB - We develop a series of molecular dynamics computer simulations of liquid water, performed with a polarizable potential model, to calculate the spinodal line and the curve of maximum density inside the metastable supercooled region. After analyzing the structural properties, the liquid spinodal line is followed down to T=210K . A monotonic decrease is found in the explored region. The curve of maximum density bends on approaching the spinodal line. These results, in agreement with similar studies on nonpolarizable models of water, are consistent with the existence of a second critical point for water. PMID- 17358138 TI - Effect of water-wall interaction potential on the properties of nanoconfined water. AB - Much of the understanding of bulk liquids has progressed through study of the limiting case in which molecules interact via purely repulsive forces, such as a hard-core or "repulsive ramp" potential. In the same spirit, we report progress on the understanding of confined water by examining the behavior of waterlike molecules interacting with planar walls via purely repulsive forces and compare our results with those obtained for Lennard-Jones (LJ) interactions between the molecules and the walls. Specifically, we perform molecular dynamics simulations of 512 waterlike molecules interacting via the TIP5P potential and confined between two smooth planar walls that are separated by 1.1nm . At this separation, there are either two or three molecular layers of water, depending on density. We study two different forms of repulsive confinement, when the water-wall interaction potential is either (i) 1r;{9} or (ii) a WCA-like repulsive potential. We find that the thermodynamic, dynamic, and structural properties of the liquid in purely repulsive confinements qualitatively match those for a system with a pure LJ attraction to the wall. In previous studies that include attractions, freezing into monolayer or trilayer ice was seen for this wall separation. Using the same separation as these previous studies, we find that the crystal state is not stable with 1r;{9} repulsive walls but is stable with WCA like repulsive confinement. However, by carefully adjusting the separation of the plates with 1r;{9} repulsive interactions so that the effective space available to the molecules is the same as that for LJ confinement, we find that the same crystal phases are stable. This result emphasizes the importance of comparing systems only using the same effective confinement, which may differ from the geometric separation of the confining surfaces. PMID- 17358139 TI - Minimal size of a barchan dune. AB - Barchans are dunes of high mobility which have a crescent shape and propagate under conditions of unidirectional wind. However, sand dunes only appear above a critical size, which scales with the saturation distance of the sand flux [P. Hersen, S. Douady, and B. Andreotti, Phys. Rev. Lett. 89, 264301 (2002); B. Andreotti, P. Claudin, and S. Douady, Eur. Phys. J. B 28, 321 (2002); G. Sauermann, K. Kroy, and H. J. Herrmann, Phys. Rev. E 64, 31305 (2001)]. It has been suggested by P. Hersen, S. Douady, and B. Andreotti, Phys. Rev. Lett. 89, 264301 (2002)] that this flux fetch distance is itself constant. Indeed, this could not explain the protosize of barchan dunes, which often occur in coastal areas of high litoral drift, and the scale of dunes on Mars. In the present work, we show from three-dimensional calculations of sand transport that the size and the shape of the minimal barchan dune depend on the wind friction speed and the sand flux on the area between dunes in a field. Our results explain the common appearance of barchans a few tens of centimeter high which are observed along coasts. Furthermore, we find that the rate at which grains enter saltation on Mars is one order of magnitude higher than on Earth, and is relevant to correctly obtain the minimal dune size on Mars. PMID- 17358140 TI - Critical packing in granular shear bands. AB - In a realistic three-dimensional setup, we simulate the slow deformation of idealized granular media composed of spheres undergoing an axisymmetric triaxial shear test. We follow the self-organization of the spontaneous strain localization process leading to a shear band and demonstrate the existence of a critical packing density inside this failure zone. The asymptotic criticality arising from the dynamic equilibrium of dilation and compaction is found to be restricted to the shear band, while the density outside of it keeps the memory of the initial packing. The critical density of the shear band depends on friction (and grain geometry) and in the limit of infinite friction it defines a specific packing state, namely the dynamic random loose packing. PMID- 17358141 TI - Computer simulation of model cohesive powders: influence of assembling procedure and contact laws on low consolidation states. AB - Molecular dynamics simulations are used to investigate the structure and mechanical properties of a simple two-dimensional model of a cohesive granular material. Intergranular forces involve elasticity, Coulomb friction, and a short range attraction akin to the van der Waals force in powders. The effects of rolling resistance (RR) at intergranular contacts are also studied. The microstructure of the cohesive packing under low pressure is shown to depend sensitively on the assembling procedure which is applied to the initially isolated particles of a granular gas. While a direct compression produces a final equilibrated configuration with a similar density to that of cohesionless systems, the formation of large aggregates prior to the application of an external pressure results in much looser stable packings. A crucial state variable is the ratio P;{*}=PaF_{0} of applied pressure P , acting on grains of diameter a , to maximum tensile contact force F0 . At low P;{*} the force carrying structure and force distribution are sensitive to the level of velocity fluctuations in the early stages of cluster aggregation. The coordination number of packings with RR approaches 2 in the limit of low initial velocities or large rolling friction. In general the force network is composed of hyperstatic clusters, typically comprising four to a few tens of grains, in which forces reach values of the order of F0 , joined by barely rigid arms, where contact forces are very small. Under growing P;{*} , it quickly rearranges into force chainlike patterns that are more familiar in dense systems. Density correlations are interpreted in terms of a fractal structure, up to a characteristic correlation length xi of the order of ten particle diameters for the studied solid fractions. The fractal dimension in systems with RR coincides, within measurement uncertainties, with the ballistic aggregation result, in spite of a possibly different connectivity, but is apparently higher without RR. Possible effects of micromechanical and assembling process parameters on mechanical strength of packings are evoked. PMID- 17358142 TI - Phase separation of a driven granular gas in annular geometry. AB - This work investigates phase separation of a monodisperse gas of inelastically colliding hard disks confined in a two-dimensional annulus, the inner circle of which represents a "thermal wall." When described by granular hydrodynamic equations, the basic steady state of this system is an azimuthally symmetric state of increased particle density at the exterior circle of the annulus. When the inelastic energy loss is sufficiently large, hydrodynamics predicts spontaneous symmetry breaking of the annular state, analogous to the van der Waals-like phase separation phenomenon previously found in a driven granular gas in rectangular geometry. At a fixed aspect ratio of the annulus, the phase separation involves a "spinodal interval" of particle area fractions, where the gas has negative compressibility in the azimuthal direction. The heat conduction in the azimuthal direction tends to suppress the instability, as corroborated by a marginal stability analysis of the basic steady state with respect to small perturbations. To test and complement our theoretical predictions we performed event-driven molecular dynamics (MD) simulations of this system. We clearly identify the transition to phase separated states in the MD simulations, despite large fluctuations present, by measuring the probability distribution of the amplitude of the fundamental Fourier mode of the azimuthal spectrum of the particle density. We find that the instability region, predicted from hydrodynamics, is always located within the phase separation region observed in the MD simulations. This implies the presence of a binodal (coexistence) region, where the annular state is metastable. The phase separation persists when the driving and elastic walls are interchanged, and also when the elastic wall is replaced by weakly inelastic one. PMID- 17358143 TI - Shear zones in granular materials: optimization in a self-organized random potential. AB - We introduce a model to describe the wide shear zones observed in modified Couette cell experiments with granular material. The model is a generalization of the recently proposed approach based on a variational principle. The instantaneous shear band is identified with the surface that minimizes the dissipation in a random potential that is biased by the local velocity difference and pressure. The apparent shear zone is the ensemble average of the instantaneous shear bands. The numerical simulation of this model matches excellently with experiments and has measurable predictions. PMID- 17358144 TI - Macroion virial contribution to the osmotic pressure in charge-stabilized colloidal suspensions. AB - Our interest goes to the different virial contributions to the equation of state of charged colloidal suspensions. Neglect of surface effects in the computation of the colloidal virial term leads to spurious and paradoxical results. This pitfall is one of the several facets of the danger of a naive implementation of the so called one component model, where the microionic degrees of freedom are integrated out to only keep in the description the mesoscopic (colloidal) degrees of freedom. On the other hand, due incorporation of wall induced forces dissolves the paradox brought forth in the naive approach, provides a consistent description, and confirms that for salt-free systems, the colloidal contribution to the pressure is dominated by the microionic one. Much emphasis is put on the no salt case but the situation with added electrolyte is also discussed. PMID- 17358145 TI - Hard-sphere fluid adsorbed in an annular wedge: the depletion force of hard-body colloidal physics. AB - Many important issues of colloidal physics can be expressed in the context of inhomogeneous fluid phenomena. When two large colloids approach one another in solvent, they interact at least partly by the response of the solvent to finding itself adsorbed in the annular wedge formed between the two colloids. At shortest range, this fluid mediated interaction is known as the depletion force/interaction because solvent is squeezed out of the wedge when the colloids approach closer than the diameter of a solvent molecule. An equivalent situation arises when a single colloid approaches a substrate/wall. Accurate treatment of this interaction is essential for any theory developed to model the phase diagrams of homogeneous and inhomogeneous colloidal systems. The aim of our paper is a test of whether or not we possess sufficient knowledge of statistical mechanics that can be trusted when applied to systems of large size asymmetry and the depletion force in particular. When the colloid particles are much larger than a solvent diameter, the depletion force is dominated by the effective two body interaction experienced by a pair of solvated colloids. This low concentration limit of the depletion force has therefore received considerable attention. One route, which can be rigorously based on statistical mechanical sum rules, leads to an analytic result for the depletion force when evaluated by a key theoretical tool of colloidal science known as the Derjaguin approximation. A rival approach has been based on the assumption that modern density functional theories (DFT) can be trusted for systems of large size asymmetry. Unfortunately, these two theoretical predictions differ qualitatively for hard sphere models, as soon as the solvent density is higher than about 23 that at freezing. Recent theoretical attempts to understand this dramatic disagreement have led to the proposal that the Derjaguin and DFT routes represent opposite limiting behavior, for very large size asymmetry and molecular sized mixtures, respectively. This proposal implies that nanocolloidal systems lie in between the two limits, so that the depletion force no longer scales linearly with the colloid radius. That is, by decreasing the size ratio from mesoscopic to molecular sized solutes, one moves smoothly between the Derjaguin and the DFT predictions for the depletion force scaled by the colloid radius. We describe the results of a simulation study designed specifically as a test of compatibility with this complex scenario. Grand canonical simulation procedures applied to hard-sphere fluid adsorbed in a series of annular wedges, representing the depletion regime of hard-body colloidal physics, confirm that neither the Derjaguin approximation, nor advanced formulations of DFT, apply at moderate to high solvent density when the geometry is appropriate to nanosized colloids. Our simulations also allow us to report structural characteristics of hard-body solvent adsorbed in hard annular wedges. Both these aspects are key ingredients in the proposal that unifies the disparate predictions, via the introduction of new physics. Our data are consistent with this proposed physics, although as yet limited to a single colloidal size asymmetry. PMID- 17358146 TI - Point-defect dynamics in two-dimensional colloidal crystals. AB - We study the topological configurations and dynamics of individual point defect vacancies and interstitials in a two-dimensional crystal of colloids interacting via a repulsive Yukawa potential. Our Brownian dynamics simulations show that the diffusion mechanism for vacancy defects occurs in two phases. The defect can glide along the crystal lattice directions, and it can rotate during an excited topological transition configuration to assume a different direction for the next period of gliding. The results for the vacancy defects are in good agreement with recent experiments. For interstitial point defects, which were not studied in the experiments, we find several of the same modes of motion as in the vacancy defect case along with two additional diffusion pathways. The interstitial defects are more mobile than the vacancy defects due to the more two-dimensional nature of the diffusion of the interstitial defects. PMID- 17358147 TI - Line tension and excess energy of a wall Plateau border. AB - We have calculated the equilibrium shape of the axially symmetric Plateau border (PB) along which a spherical bubble contacts a flat wall, by numerical integration of Laplace's equation. We found that the (spherical) film prolongation into the PB meets the wall at an internal angle varphi